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Zimmer A, Horneff G. An update on the safety of biologic therapies for the treatment of polyarticular juvenile idiopathic arthritis. Expert Opin Drug Saf 2025; 24:627-642. [PMID: 39946290 DOI: 10.1080/14740338.2025.2467179] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2024] [Accepted: 01/29/2025] [Indexed: 02/18/2025]
Abstract
INTRODUCTION An increasing number of patients with polyarticular course juvenile idiopathic arthritis are treated with biologics with great efficacy. Consequently, the importance regarding safety data in general as well as especially serious infections, incident autoimmune processes, or malignancies rises. In children, this is crucial concerning occurrences that manifest rarely and only after a prolonged latency period. AREAS COVERED This study aims to analyze safety under therapy with the five most commonly used biologicals for the treatment of juvenile idiopathic arthritis in Germany: abatacept, adalimumab, etanercept, golimumab, and tocilizumab, and a control cohort, who received methotrexate. For this, data from the Biologics in Pediatric Rheumatology (BiKeR) Registry were analyzed with a focus on potential adverse drug reactions like serious infections, autoimmune processes or malignancies. EXPERT OPINION Besides JIA category-specific differences, investigating side effects like severe infections and the development of additional autoimmune processes due to therapy is crucial. Future clinical randomized double-blinded studies are essential for direct drug comparisons, enabling optimal individualized therapy considering comorbidities and individual risks. Large patient data over a (life-)long period beyond childhood are particularly important, especially concerning the risk of malignancy after prolonged latency.
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Affiliation(s)
- Angela Zimmer
- Department of Pediatric Rheumatology, Asklepios Clinic Sankt Augustin, Sankt Augustin, Germany
| | - Gerd Horneff
- Department of Pediatric Rheumatology, Asklepios Clinic Sankt Augustin, Sankt Augustin, Germany
- University Hospital of Cologne, Köln, Germany
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Li B, Li C, Zhong XJ, Xu XR. Depression and anxiety, peripheral blood inflammatory factors, and stress levels on therapeutic outcomes in patients with chronic wounds. World J Psychiatry 2024; 14:1836-1844. [PMID: 39704378 PMCID: PMC11622014 DOI: 10.5498/wjp.v14.i12.1836] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2024] [Revised: 10/29/2024] [Accepted: 11/08/2024] [Indexed: 11/27/2024] Open
Abstract
BACKGROUND The incidence of chronic wounds is rising due to an aging population and lifestyle changes in our country. In addition, as the disease spectrum evolves, chronic wounds have become common clinical issues that seriously threaten health and impose significant social and economic burdens. AIM To investigate how depression, anxiety, peripheral blood inflammatory factors, and stress levels affect therapeutic outcomes in patients with chronic wounds. METHODS Retrospectively collected clinical data from 110 patients with chronic wounds treated at Changde Hospital, Xiangya School of Medicine, Central South University (The First People's Hospital of Changde City) between January 2021 and December 2023, categorizing them into effective and ineffective groups based on treatment effects. Differences between both groups were analyzed using univariate analysis, independent risk factors identified via logistic regression, and their predictive value assessed through receiver operating characteristic analysis. RESULTS Following treatment, 95 cases were classified as the effective group (cured or improved), while 15 cases with improvement formed the ineffective group. Significant differences between both groups were noted in wound area, infection status, daily bed time, Hamilton Anxiety Rating Scale (HAMA) scores, Hamilton Depression Rating Scale (HAMD) scores, and levels of interleukin-6, tumor necrosis factor-alpha, and superoxide dismutase (P < 0.05). Logistic regression analysis identified a wound area ≥ 7 cm2, HAMA ≥ 9 scores, and HAMD ≥ 8 scores were independent risk factors for ineffective treatment in patients with chronic wounds (P < 0.05). The receiver operating characteristic curve analysis revealed that the area under the curve for ineffective treatment based on wound area, HAMA, and HAMD was 0.767, 0.805, and 0.768 respectively. CONCLUSION Wound size, anxiety, and depression are significant factors influencing the therapeutic outcomes in patients with chronic wounds that require careful attention, alongside the development of appropriate strategies.
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Affiliation(s)
- Bo Li
- Department of Burns and Plastic Surgery, Changde Hospital, Xiangya School of Medicine, Central South University (The First People’s Hospital of Changde City), Changde 415000, Hunan Province, China
| | - Cha Li
- Department of Pediatric Intensive Care Unit, Changde Hospital, Xiangya School of Medicine, Central South University (The First People’s Hospital of Changde City), Changde 415000, Hunan Province, China
| | - Xian-Jiang Zhong
- Department of Psychiatry, The First People’s Hospital of Xiantao, Xiantao 433099, Hubei Province, China
| | - Xiang-Rong Xu
- Department of Burns and Plastic Surgery, Changde Hospital, Xiangya School of Medicine, Central South University (The First People’s Hospital of Changde City), Changde 415000, Hunan Province, China
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Yang J, Wang J, Ding B, Jiang Z, Yu F, Li D, Sun W, Wang L, Xu H, Hu S. Feedback delivery of BMP 7 on the pathological oxidative stress via smart hyaluronic acid hydrogel potentiated the repairing of the gut epithelial integrity. Int J Biol Macromol 2024; 282:136794. [PMID: 39447783 DOI: 10.1016/j.ijbiomac.2024.136794] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2024] [Revised: 10/09/2024] [Accepted: 10/20/2024] [Indexed: 10/26/2024]
Abstract
The intestinal barrier integrity was substantially collapsed when colitis flaring up, accompanying by the hallmark of pathological oxidative stress. Bone morphogenetic protein 7 (BMP 7), an endogenous growth factor in gut had the potential to repair the damaged mucosa. Herein, a smart hydrogel (HDP) had been developed by the boronate-ester crosslinked hyaluronic acid to deliver BMP 7. Hydrogel loading BMP 7 (HDP-BMP 7) presented the comparable mechanical strength with that of the naïve gut mucus. HDP-BMP 7 as artificial mucus could specifically adhere to the inflamed colonic mucosa of colitis mice. Importantly, it could apperceive reactive oxygen species at diseased colon to adapt its intrinsic network, enabling the feedback release of BMP 7 on the pathological oxidative stress. Moreover, in vivo animal experiments showed that the disease symptoms of colitis mice were alleviated by HDP-BMP 7. Importantly, both the mucus barrier and the epithelial barriers were obviously recovered by HDP-BMP 7 treatment, which substantially attenuated the immune-inflammation response of colitis mice. Besides, HDP-BMP 7 enriched the diversity of gut flora, increasing the relative abundance of Lactobacillus and decreasing the ratio of Firmicutes/Bacteroidetes. Its therapeutic mechanism was associated with activating TGF-β/Smad signals. Conclusively, this smart hydrogel might potentiate the repairing effect of growth factors on the gut epithelial integrity.
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Affiliation(s)
- Jiaojiao Yang
- Department of Gastroenterology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou City, Zhejiang Province 325000, China; Department of Pharmaceutics, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou City, Zhejiang Province 325035, China
| | - Jie Wang
- Department of Pharmaceutics, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou City, Zhejiang Province 325035, China
| | - Bingyu Ding
- Department of Pharmaceutics, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou City, Zhejiang Province 325035, China
| | - Zhijiang Jiang
- Department of Pharmaceutics, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou City, Zhejiang Province 325035, China
| | - Fengnan Yu
- Department of Pharmaceutics, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou City, Zhejiang Province 325035, China
| | - Dingwei Li
- Department of Pharmaceutics, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou City, Zhejiang Province 325035, China
| | - Wenwen Sun
- Pathology Department, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou City, Zhejiang Province 325035, China
| | - Lifen Wang
- Research Center for Drug Safety Evaluation, Hainan Medical University, Haikou City, Hainan Province, China.
| | - Helin Xu
- Department of Pharmaceutics, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou City, Zhejiang Province 325035, China.
| | - Sunkuan Hu
- Department of Gastroenterology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou City, Zhejiang Province 325000, China.
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Bakhashab S, Banafea GH, Ahmed F, Alsolami R, Schulten HJ, Gauthaman K, Naseer MI, Pushparaj PN. Acute and prolonged effects of interleukin-33 on cytokines in human cord blood-derived mast cells. Immunol Lett 2024; 269:106908. [PMID: 39151731 DOI: 10.1016/j.imlet.2024.106908] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2024] [Revised: 07/11/2024] [Accepted: 08/08/2024] [Indexed: 08/19/2024]
Abstract
Mast cells are multifaceted cells localized in tissues and possess various surface receptors that allow them to respond to inner and external threat signals. Interleukin-33 (IL-33) is a cytokine released by structural cells in response to parasitic infections, mechanical damage, and cell death. IL-33 can activate mast cells, causing them to release an array of mediators. This study aimed to identify the different cytokines released by human cord blood-derived mast cells (hCBMCs) in response to acute and prolonged stimulation with IL-33. For this purpose, a hCBMC model was established and stimulated with 10 ng and 20 ng of recombinant human IL-33 (rhIL-33) for 6 h and 24 h. Total RNA was hybridized using a high-density oligonucleotide microarray. A multiplex assay was performed to assess the released cytokines. Acute exposure to rhIL-33 increased the expression of IL-1α, IL-1β, IL-6, and IL-13, whereas prolonged exposure increased the expression of IL-5 and IL-10, and cytokines were detected in the culture supernatant. WebGestalt analysis revealed that rhIL-33 induces pathways and biological processes related to the immune system and the acute inflammatory response. This study demonstrates that rhIL-33 can activate hCBMCs to release pro- and anti-inflammatory cytokines, eliciting distinct acute and prolonged responses unique to hCBMCs.
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Affiliation(s)
- Sherin Bakhashab
- Department of Biochemistry, King Abdulaziz University, Jeddah, Saudi Arabia; Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia.
| | - Ghalya H Banafea
- Department of Biochemistry, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Farid Ahmed
- Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia; Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Reem Alsolami
- Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Hans-Juergen Schulten
- Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia; Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Kalamegam Gauthaman
- Center for Transdisciplinary Research, Department of Pharmacology, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India
| | - Muhammad Imran Naseer
- Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia; Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Peter Natesan Pushparaj
- Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia; Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia; Center for Transdisciplinary Research, Department of Pharmacology, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India.
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Saadh MJ, Ahmed HH, Singh A, Mustafa MA, Al Zuhairi RAH, Ghildiyal P, Jawad MJ, Alsaikhan F, Khalilollah S, Akhavan-Sigari R. Small molecule and big function: MicroRNA-mediated apoptosis in rheumatoid arthritis. Pathol Res Pract 2024; 261:155508. [PMID: 39116571 DOI: 10.1016/j.prp.2024.155508] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2024] [Revised: 07/24/2024] [Accepted: 07/29/2024] [Indexed: 08/10/2024]
Abstract
Rheumatoid arthritis (RA) is a common autoimmune condition and chronic inflammatory disease, mostly affecting synovial joints. The complex pathogenesis of RA is supportive of high morbidity, disability, and mortality rates. Pathological changes a common characteristic in RA synovial tissue is attributed to the inadequacy of apoptotic pathways. In that regard, apoptotic pathways have been the center of attention in RA therapeutic approaches. As the regulators in the complex network of apoptosis, microRNAs (miRNAs) are found to be vital modulators in both intrinsic and extrinsic pathways through altering their regulatory genes. Indeed, miRNA, a member of the family of non-coding RNAs, are found to be an important player in not even apoptosis, but proliferation, gene expression, signaling pathways, and angiogenesis. Aberrant expression of miRNAs is implicated in attenuation and/or intensification of various apoptosis routes, resulting in culmination of human diseases including RA. Considering the need for more studies focused on the underlying mechanisms of RA in order to elevate the unsatisfactory clinical treatments, this study is aimed to delineate the importance of apoptosis in the pathophysiology of this disease. As well, this review is focused on the critical role of miRNAs in inducing or inhibiting apoptosis of RA-synovial fibroblasts and fibroblast-like synoviocytes and how this mechanism can be exerted for therapeutic purposes for RA.
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Affiliation(s)
- Mohamed J Saadh
- Faculty of Pharmacy, Middle East University, Amman 11831, Jordan.
| | | | - Anamika Singh
- Department of Biotechnology and Genetics, Jain (Deemed-to-be) University, Bengaluru, Karnataka 560069, India; Department of Allied Healthcare and Sciences, Vivekananda Global University, Jaipur, Rajasthan 303012, India
| | - Mohammed Ahmed Mustafa
- School of Pharmacy-Adarsh Vijendra Institute of Pharmaceutical Sciences, Shobhit University, Gangoh, Uttar Pradesh-247341, India; Department of Pharmacy, Arka Jain University, Jamshedpur, Jharkhand- 831001, India.
| | | | - Pallavi Ghildiyal
- Uttaranchal Institute of Pharmaceutical Sciences, Uttaranchal University, Dehradun, India.
| | | | - Fahad Alsaikhan
- College of Pharmacy, Prince Sattam Bin Abdulaziz University, Alkharj, Saudi Arabia; School of Pharmacy, Ibn Sina National College for Medical Studies, Jeddah, Saudi Arabia.
| | - Shayan Khalilollah
- Department of Neurosurgery, Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Reza Akhavan-Sigari
- Department of Neurosurgery, University Medical Center Tuebingen, Germany; Department of Health Care Management and Clinical Research, Collegium Humanum Warsaw Management University Warsaw, Poland
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Sukmak P, Kulworasreth P, Treveeravoot S, Arinno A, Anuwongworavet S, Wachiradejkul W, Kulworasreth P, Teansuk N, Thongnak L, Amonlerdpison D, Inchai J, Jakrachai C, Akrimajirachoote N, Aonbangkhen C, Muanprasat C, Poolsri W, Vaddhanaphuti CS, Pongkorpsakol P. Solanum melongena L. Extract Promotes Intestinal Tight Junction Re-Assembly via SIRT-1-Dependent Mechanisms. Mol Nutr Food Res 2024; 68:e2400230. [PMID: 39086054 DOI: 10.1002/mnfr.202400230] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2024] [Revised: 06/30/2024] [Indexed: 08/02/2024]
Abstract
Tight junction disruption can lead to pathogenesis of various diseases without therapeutic strategy to recover intestinal barrier integrity. The main objective of this study is to demonstrate the effect of Solanum melongena L. extract (SMLE) on intestinal tight junction recovery and its underlying mechanism. Intestinal barrier function is attenuated by Ca2+ depletion. SMLE treatment increased TER value across T84 cell monolayers. Permeability assay reveals that Ca2+ depletion promotes 4-kDa FITC-dextran permeability, but not 70-kDa FITC-dextran. SMLE suppresses the rate of 4-kDa FITC-dextran permeability, indicating that SMLE inhibits paracellular leak pathway permeability. SMLE-mediated TER increase and leak pathway suppression are abolished by neither calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ) inhibitor nor AMP-activated protein kinase (AMPK) inhibitor. Furthermore, mammalian target of rapamycin (mTOR) and extracellular signal-regulated kinase (ERK) inhibitors have no effects on SMLE-mediated TER increase and leak pathway suppression. Interestingly, SMLE is unable to enhance TER value and diminish leak pathway permeability in T84 cell monolayers pre-treated with sirtuin-1 (SIRT-1) inhibitor. Immunofluorescence staining reveals that SMLE enhances re-assembly of tight junction proteins, including occludin and ZO-1 to intercellular space but this effect is abolished by SIRT-1 inhibitor. These data suggest that SMLE promotes intestinal tight junction re-assembly via SIRT-1-dependent manner.
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Affiliation(s)
- Pichayapa Sukmak
- Princess Srisavangavadhana College of Medicine, Chulabhorn Royal Academy, Bangkok, Thailand
- Laboratory of Epithelial Tight Junction Pathophysiology, Bangkok, Thailand
| | - Purisha Kulworasreth
- Princess Srisavangavadhana College of Medicine, Chulabhorn Royal Academy, Bangkok, Thailand
| | - Supisara Treveeravoot
- Princess Srisavangavadhana College of Medicine, Chulabhorn Royal Academy, Bangkok, Thailand
- Laboratory of Epithelial Tight Junction Pathophysiology, Bangkok, Thailand
| | - Apiwan Arinno
- Princess Srisavangavadhana College of Medicine, Chulabhorn Royal Academy, Bangkok, Thailand
- Laboratory of Epithelial Tight Junction Pathophysiology, Bangkok, Thailand
- Center of Excellence in Natural Products Chemistry (CENP), Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok, Thailand
| | | | - Wanapas Wachiradejkul
- Princess Srisavangavadhana College of Medicine, Chulabhorn Royal Academy, Bangkok, Thailand
| | - Purit Kulworasreth
- Princess Srisavangavadhana College of Medicine, Chulabhorn Royal Academy, Bangkok, Thailand
| | - Natnicha Teansuk
- Princess Srisavangavadhana College of Medicine, Chulabhorn Royal Academy, Bangkok, Thailand
- Laboratory of Epithelial Tight Junction Pathophysiology, Bangkok, Thailand
| | - Laongdao Thongnak
- Princess Srisavangavadhana College of Medicine, Chulabhorn Royal Academy, Bangkok, Thailand
| | - Doungporn Amonlerdpison
- Center of Excellence in Agricultural Innovation for Graduate Entrepreneur and Faculty of Fisheries Technology and Aquatic Resources, Maejo University, Chiang Mai, Thailand
| | - Jakkapong Inchai
- Innovative Research Unit of Epithelial Transport and Regulation (iETR), Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Chaiwet Jakrachai
- Innovative Research Unit of Epithelial Transport and Regulation (iETR), Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | | | - Chanat Aonbangkhen
- Center of Excellence in Natural Products Chemistry (CENP), Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok, Thailand
| | - Chatchai Muanprasat
- Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Samut Prakan, Thailand
| | | | - Chutima S Vaddhanaphuti
- Innovative Research Unit of Epithelial Transport and Regulation (iETR), Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Pawin Pongkorpsakol
- Princess Srisavangavadhana College of Medicine, Chulabhorn Royal Academy, Bangkok, Thailand
- Laboratory of Epithelial Tight Junction Pathophysiology, Bangkok, Thailand
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Choreño-Parra JA, Ramon-Luing LA, Castillejos M, Ortega-Martínez E, Tapia-García AR, Matías-Martínez MB, Cruz-Lagunas A, Ramírez-Martínez G, Gómez-García IA, Ramírez-Noyola JA, Garcia-Padrón B, López-Salinas KG, Jiménez-Juárez F, Guadarrama-Ortiz P, Salinas-Lara C, Bozena-Piekarska K, Muñóz-Torrico M, Chávez-Galán L, Zúñiga J. The rs11684747 and rs55790676 SNPs of ADAM17 influence tuberculosis susceptibility and plasma levels of TNF, TNFR1, and TNFR2. Front Microbiol 2024; 15:1392782. [PMID: 38881671 PMCID: PMC11177089 DOI: 10.3389/fmicb.2024.1392782] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2024] [Accepted: 05/15/2024] [Indexed: 06/18/2024] Open
Abstract
Introduction The proteolytic activity of A Disintegrin and Metalloproteinase 17 (ADAM17) regulates the release of tumor necrosis factor (TNF) and TNF receptors (TNFRs) from cell surfaces. These molecules play important roles in tuberculosis (TB) shaping innate immune reactions and granuloma formation. Methods Here, we investigated whether single nucleotide polymorphisms (SNPs) of ADAM17 influence TNF and TNFRs levels in 224 patients with active TB (ATB) and 118 healthy close contacts. Also, we looked for significant associations between SNPs of ADAM17 and ATB status. TNF, TNFR1, and TNFR2 levels were measured in plasma samples by ELISA. Four SNPs of ADAM17 (rs12692386, rs1524668, rs11684747, and rs55790676) were analyzed in DNA isolated from peripheral blood leucocytes. The association between ATB status, genotype, and cytokines was analyzed by multiple regression models. Results Our results showed a higher frequency of rs11684747 and rs55790676 in close contacts than ATB patients. Coincidentally, heterozygous to these SNPs of ADAM17 showed higher plasma levels of TNF compared to homozygous to their respective ancestral alleles. Strikingly, the levels of TNF and TNFRs distinguished participant groups, with ATB patients displaying lower TNF and higher TNFR1/TNFR2 levels compared to their close contacts. Conclusion These findings suggest a role for SNPs of ADAM17 in genetic susceptibility to ATB.
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Affiliation(s)
- José Alberto Choreño-Parra
- Dirección de Enseñanza, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas, Mexico City, Mexico
- Laboratory of Immunobiology and Genetics, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, Mexico
| | - Lucero A Ramon-Luing
- Laboratory of Integrative Immunology, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, Mexico
| | - Manuel Castillejos
- Departamento de Epidemiología Hospitalaria e Infectología, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, Mexico
| | - Emmanuel Ortega-Martínez
- Posgrado en Ciencias Quimicobiológicas, SEPI, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Mexico City, Mexico
- Department of Pathology, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, Mexico City, Mexico
- Red MEDICI, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla de Baz, Mexico
| | - Alan Rodrigo Tapia-García
- Laboratory of Immunobiology and Genetics, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, Mexico
- Red MEDICI, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla de Baz, Mexico
| | - Melvin Barish Matías-Martínez
- Laboratory of Immunobiology and Genetics, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, Mexico
- Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Mexico City, Mexico
| | - Alfredo Cruz-Lagunas
- Laboratory of Immunobiology and Genetics, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, Mexico
| | - Gustavo Ramírez-Martínez
- Laboratory of Immunobiology and Genetics, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, Mexico
| | - Itzel Alejandra Gómez-García
- Laboratory of Immunobiology and Genetics, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, Mexico
- Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Mexico City, Mexico
| | - Jazmín Ariadna Ramírez-Noyola
- Laboratory of Immunobiology and Genetics, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, Mexico
- Sección de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico City, Mexico
| | - Beatriz Garcia-Padrón
- Laboratory of Immunobiology and Genetics, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, Mexico
- Red MEDICI, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla de Baz, Mexico
| | - Karen Gabriel López-Salinas
- Laboratory of Immunobiology and Genetics, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, Mexico
- Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Mexico City, Mexico
| | - Fabiola Jiménez-Juárez
- Laboratory of Immunobiology and Genetics, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, Mexico
- Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Mexico City, Mexico
| | | | - Citlaltepetl Salinas-Lara
- Department of Pathology, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, Mexico City, Mexico
- Red MEDICI, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla de Baz, Mexico
| | - Karolina Bozena-Piekarska
- Dirección de Enseñanza, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas, Mexico City, Mexico
| | - Marcela Muñóz-Torrico
- Clínica de Tuberculosis, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, Mexico
| | - Leslie Chávez-Galán
- Laboratory of Integrative Immunology, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, Mexico
| | - Joaquín Zúñiga
- Laboratory of Immunobiology and Genetics, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, Mexico
- Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Mexico City, Mexico
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Bastard L, Claudepierre P, Penso L, Sbidian E, Pina Vegas L. Risk of serious infection associated with different classes of targeted therapies used in psoriatic arthritis: a nationwide cohort study from the French Health Insurance Database (SNDS). RMD Open 2024; 10:e003865. [PMID: 38485454 PMCID: PMC10941117 DOI: 10.1136/rmdopen-2023-003865] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2023] [Accepted: 02/20/2024] [Indexed: 03/17/2024] Open
Abstract
OBJECTIVE To assess the risk of serious infection associated with different targeted therapies for psoriatic arthritis (PsA) in real-world settings. METHODS This nationwide cohort study used the administrative healthcare database of the French health insurance scheme linked to the hospital discharge database to identify all adults with PsA who were new users of targeted therapies (adalimumab, etanercept, golimumab, certolizumab pegol, infliximab, secukinumab, ixekizumab, ustekinumab, and tofacitinib) from 1 January 2015 to 30 June 2021. The primary outcome was a serious infection (ie, requiring hospitalisation), in a time-to-event analysis using propensity score-weighted Cox models, with adalimumab as the comparator, estimating weighted HRs (wHRs) and their 95% CIs. RESULTS A total of 12 071 patients were included (mean age 48.7±12.7 years; 6965 (57.7%) women). We identified 367 serious infections (3.0% of patients), with a crude incidence rate of 17.0 per 1000 person-years (95% CI, 15.2 to 18.7). After inverse propensity score weighting and adjustment for time-dependent covariates and calendar year, risk of serious infection was significantly lower for new users of etanercept (wHR 0.72; 95% CI, 0.53 to 0.97) or ustekinumab (wHR, 0.57; 95% CI, 0.35 to 0.93) than adalimumab new users. This risk was not statistically modified with the other targeted therapies. CONCLUSIONS The incidence of serious infection was low for PsA patients who were new users of targeted therapies in real-world settings. Relative to adalimumab new users, this risk was lower among new users of etanercept and ustekinumab and unmodified for the other molecules.
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Affiliation(s)
- Léa Bastard
- Epidemiology in Dermatology and Evaluation of Therapeutics (EpiDermE), University Paris-Est Créteil Val de Marne, Créteil, France
- Rheumatology, Hospital Henri Mondor, Créteil, France
| | - Pascal Claudepierre
- Epidemiology in Dermatology and Evaluation of Therapeutics (EpiDermE), University Paris-Est Créteil Val de Marne, Créteil, France
- Rheumatology, Hospital Henri Mondor, Créteil, France
| | - Laetitia Penso
- Epidemiology in Dermatology and Evaluation of Therapeutics (EpiDermE), University Paris-Est Créteil Val de Marne, Créteil, France
| | - Emilie Sbidian
- Epidemiology in Dermatology and Evaluation of Therapeutics (EpiDermE), University Paris-Est Créteil Val de Marne, Créteil, France
- Dermatology, Hospital Henri Mondor, Créteil, France
- Clinical Investigation Center 1430, INSERM, Créteil, France
| | - Laura Pina Vegas
- Epidemiology in Dermatology and Evaluation of Therapeutics (EpiDermE), University Paris-Est Créteil Val de Marne, Créteil, France
- Rheumatology, Hospital Henri Mondor, Créteil, France
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9
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Railton J, Volonté M, Isoletta E, Bonelli A, Barruscotti S, Brazzelli V. Psoriasis and biological drugs at the time of SARS-CoV-2 infection: a mini review outlining risk of infection, seroprevalence, and safety and efficacy of the BNT162b2 vaccine. Front Immunol 2024; 15:1354729. [PMID: 38352875 PMCID: PMC10861681 DOI: 10.3389/fimmu.2024.1354729] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2023] [Accepted: 01/09/2024] [Indexed: 02/16/2024] Open
Abstract
Objective The aim of this study is to review the life of patients with psoriasis on biologic therapy during the SARS-CoV-2 pandemic and the relevance of frailty within this context, reviewing studies that describe the course and severity of infection in patients with psoriasis on biologics, the seroprevalence of SARS-CoV-2, and the safety and efficacy of the BNT162b2 vaccine in these patients. Materials and methods The keywords "Psoriasis," "Biologics," "SARS-CoV-2," "COVID-19," and "BNT162b2 Vaccine" were used in various combinations on database engines to find relevant articles on this topic. Results A total of 36 articles were found, with 20 concerning the course, severity, and seroprevalence of SARS-CoV-2 in patients with psoriasis on biologic therapy and 16 concerning safety and efficacy of BNT162b2 in these patients. Discussion Patients with psoriasis on biologic therapy did not have increased seroprevalence compared with the general population, indicating that they were not at an increased risk of SARS-CoV-2 infection compared with the general population. Furthermore, the immunosuppressive action of biologics may be protective, as patients on biologic therapy had better outcomes and less risk of severe infection. The seroconversion rate against SARS-CoV-2 from the BNT162b2 vaccine was similar in both patients with psoriasis on biologics and the general population, indicating that efficacy is not hindered by the biologic therapy. However, the cellular response in population with psoriasis was significantly less intense, and the humoral immune response was weaker than that in the general population, demonstrating that the possibility of tighter vaccination schedules and additional doses may be advantageous in these patients.
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Affiliation(s)
- Janosch Railton
- Institute of Dermatology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Martina Volonté
- Institute of Dermatology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Eugenio Isoletta
- Institute of Dermatology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Alice Bonelli
- Institute of Dermatology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | | | - Valeria Brazzelli
- Institute of Dermatology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
- Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, Institute of Dermatology, Università degli Studi di Pavia, Pavia, Italy
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10
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Feng H, Zhao Y, Kuang W, Dai Y, Cen X, Qin F. Adverse events of tumor necrosis factor alpha inhibitors for the treatment of ankylosing spondylitis: A meta-analysis of randomized, placebo-controlled trials. Front Pharmacol 2023; 14:1084614. [PMID: 36865909 PMCID: PMC9972296 DOI: 10.3389/fphar.2023.1084614] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2022] [Accepted: 02/01/2023] [Indexed: 02/16/2023] Open
Abstract
Objective: Tumor necrosis factor alpha inhibitors (TNFi) have shown substantial efficacy in alleviating and treating ankylosing spondylitis (AS). However, the heightened interest is accompanied by concerns over adverse events. In this meta-analysis, we analyzed both serious and common adverse events in patients treated with tumor necrosis factor alpha inhibitors compared with those in the placebo group. Methods: We searched for clinical trials in PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Wanfang Data, and VIP Data. Studies were selected based on strict inclusion and exclusion criteria. Only randomized, placebo-controlled trials were included in the final analysis. RevMan 5.4 software was used for performing meta-analyses. Results: A total of 18 randomized controlled trials recruiting 3,564 patients with ankylosing spondylitis were included, with overall moderate to high methodological quality. Compared with the placebo group, the incidences showed no difference and were only slightly increased numerically for serious adverse events, serious infections, upper respiratory tract infection, and malignancies in patients treated with tumor necrosis factor alpha inhibitors. However, tumor necrosis factor alpha inhibitor treatment significantly increased the incidence of overall adverse events, nasopharyngitis, headache, and injection-site reactions in ankylosing spondylitis patients when compared with placebo. Conclusion: The available data indicated that ankylosing spondylitis patients who received tumor necrosis factor alpha inhibitors had no significantly increased risks of serious adverse events when compared with the placebo group. However, tumor necrosis factor alpha inhibitors significantly increased the incidence rate of common adverse events, including nasopharyngitis, headache, and injection-site reactions. Large-scale and long-term follow-up clinical trials are still necessary to further investigate the safety of tumor necrosis factor alpha inhibitors in ankylosing spondylitis treatment.
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Affiliation(s)
- Haihuan Feng
- State Key Laboratory of Biotherapy, Collaborative Innovation Center for Biotherapy, National Chengdu Center for Safety Evaluation of Drugs, West China Hospital, Sichuan University, Chengdu, China,Medical Insurance Office, West China Hospital, Sichuan University, Chengdu, China
| | - Ying Zhao
- State Key Laboratory of Biotherapy, Collaborative Innovation Center for Biotherapy, National Chengdu Center for Safety Evaluation of Drugs, West China Hospital, Sichuan University, Chengdu, China
| | - Weihong Kuang
- Department of Psychiatry, West China Hospital, Sichuan University, Chengdu, China
| | - Yanping Dai
- State Key Laboratory of Biotherapy, Collaborative Innovation Center for Biotherapy, National Chengdu Center for Safety Evaluation of Drugs, West China Hospital, Sichuan University, Chengdu, China
| | - Xiaobo Cen
- State Key Laboratory of Biotherapy, Collaborative Innovation Center for Biotherapy, National Chengdu Center for Safety Evaluation of Drugs, West China Hospital, Sichuan University, Chengdu, China
| | - Feng Qin
- State Key Laboratory of Biotherapy, Collaborative Innovation Center for Biotherapy, National Chengdu Center for Safety Evaluation of Drugs, West China Hospital, Sichuan University, Chengdu, China,Andrology Laboratory, Department of Urology, West China Hospital, Sichuan University, Chengdu, China,*Correspondence: Feng Qin,
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11
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Guillo L, Flachaire B, Avouac J, Dong C, Nachury M, Bouguen G, Buisson A, Caillo L, Fumery M, Gilletta C, Hébuterne X, Lafforgue P, Laharie D, Mahé E, Marotte H, Nancey S, Ottaviani S, Salmon JH, Savoye G, Serrero M, Uzzan M, Viguier M, Richez C, Peyrin-Biroulet L, Seksik P, Pham T. Efficacy and safety of combination targeted therapies in immune-mediated inflammatory disease: the COMBIO study. Dig Liver Dis 2023; 55:61-68. [PMID: 35985961 DOI: 10.1016/j.dld.2022.07.012] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2022] [Revised: 07/19/2022] [Accepted: 07/20/2022] [Indexed: 12/31/2022]
Abstract
BACKGROUND Use of a combination of targeted therapies (COMBIO) in patients with refractory/overlapping immune-mediated inflammatory diseases (IMIDs) has increased, but reported data remain scarce. We aimed to assess effectiveness and safety of COMBIO in patients with IMIDs. METHODS We conducted a French ambispective multicenter cohort study from September 2020 to May 2021, including adults' patients with 1 or 2 IMIDs and treated at least 3-month with COMBIO. RESULTS Overall, 143 patients were included. The most common IMIDs were Crohn's disease (63.6%), axial spondyloarthritis (37.7%), and ulcerative colitis (14%). Half of patients had only one IMID, of which 60% were Crohn's disease. Mean duration of COMBIO was 274.5±59.3 weeks, and COMBIO persistence at 104 weeks was estimated at 64.1%. The most frequent COMBIOs combined anti-TNF agents with vedolizumab (30%) or ustekinumab (28.7%). Overall, 50% of patients achieved significant and 27% mild-to-moderate improvement in patient-reported outcomes. Extended duration of COMBIO (aOR=1.09; 95% CI: 1.03-1.14; p=0.002) and diagnoses of two IMIDs (aOR=3.46; 95%CI: 1.29-9.26; p=0.013) were associated with significant improvement in patient-reported outcomes. Incidence of serious infection during COMBIO was 4.51 per 100 person-years (95% CI 2.20-8.27) and 5 COMBIOs were discontinued due to adverse events. CONCLUSIONS COMBIO can be effective and safe in patients with refractory/overlapping IMIDs.
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Affiliation(s)
- Lucas Guillo
- Aix Marseille Univ, APHM, University Hospital of Marseille Nord, Department of Gastroenterology, Marseille, France.
| | - Benoit Flachaire
- Aix Marseille Univ, APHM, University Hospital of Marseille Sainte-Marguerite, Department of Rheumatology, Marseille, France
| | - Jérôme Avouac
- Université de Paris, service de rhumatologie, hôpital Cochin, AP-HP.CUP, 27, rue du Faubourg-Saint-Jacques, 75014 Paris, France
| | - Catherine Dong
- Service de Gastro-Entérologie, Assistance publique-Hôpitaux de Paris (AP-HP), hôpital Bicêtre, 94270 Le Kremlin-Bicêtre, France
| | - Maria Nachury
- Université de Lille, Inserm, CHU Lille, U1286 - INFINITE - Institute for Translational Research in Inflammation, F-59000 Lille, France
| | - Guillaume Bouguen
- CHU Rennes, Univ Rennes, INSERM, CIC1414, Institut NUMECAN (Nutrition Metabolisms and Cancer), 35000 Rennes, France
| | - Anthony Buisson
- Université Clermont Auvergne, 3iHP, CHU Clermont-Ferrand, Service d'Hépato-Gastroentérologie, Inserm U1071, M2iSH, USC-INRA 2018, Clermont-Ferrand, France
| | - Ludovic Caillo
- Department of Gastroenterology, University Hospital of Nimes, Nimes, France
| | - Mathurin Fumery
- Department of Gastroenterology, Amiens University Medical Center and PeriTox UMR I-O1, Jules Verne University of Picardie, Amiens, France
| | - Cyrielle Gilletta
- Department of Gastroenterology, Toulouse University Hospital, Toulouse, France
| | - Xavier Hébuterne
- Gastroenterology and Clinical Nutrition, CHU of Nice, University Côte d'Azur, Nice, France
| | - Pierre Lafforgue
- Aix Marseille Univ, APHM, University Hospital of Marseille Sainte-Marguerite, Department of Rheumatology, Marseille, France
| | - David Laharie
- CHU de Bordeaux, Hôpital Haut-Lévêque, Service d'Hépato-gastroentérologie et oncologie digestive - Université de Bordeaux, F-33000 Bordeaux, France
| | - Emmanuel Mahé
- Dermatology Department, Hôpital Victor Dupouy, Argenteuil, France. Groupe de recherche sur le Psoriasis (GrPso) de la Société Française de Dermatologie
| | - Hubert Marotte
- Department of Rheumatology, Inserm U1059-LBTO, CHU Saint-Etienne, Saint-Etienne, France
| | - Stéphane Nancey
- Department of Gastroenterology, Inserm U1111-CIRI, Lyon-Sud University Hospital, Hospices Civils de Lyon, Pierre Bénite, France
| | - Sébastien Ottaviani
- Departement of Rheumatology, DMU Locomotion, Hôpital Bichat-Claude Bernard, APHP, Université de Paris, Paris, France
| | - Jean-Hugues Salmon
- Department of Rheumatology and EA 3797, University of Reims Champagne-Ardenne, Reims, France
| | - Guillaume Savoye
- Department of Gastroenterology, Rouen University Hospital, Rouen, France
| | - Mélanie Serrero
- Aix Marseille Univ, APHM, University Hospital of Marseille Nord, Department of Gastroenterology, Marseille, France
| | - Mathieu Uzzan
- Department of Gastroenterology, IBD unit, Beaujon Hospital, APHP, Clichy, France
| | - Manuelle Viguier
- Department of Dermatology-Venereology, Hôpital Robert Debré, Université Reims Champagne-Ardenne, Reims, France
| | - Christophe Richez
- Rheumatology Department, CHU de Bordeaux, and ImmunoConcEpt, CNRS, UMR 5164, University of Bordeaux, Bordeaux, France
| | - Laurent Peyrin-Biroulet
- Department of Gastroenterology and INSERM NGERE U1256, University Hospital of Nancy, University of Lorraine, Vandoeuvre-lès-Nancy, France
| | - Philipe Seksik
- Department of Gastroenterology, Centre de recherche Saint-Antoine, Sorbonne Université, INSERM, APHP, Hôpital Saint-Antoine, Paris, France
| | - Thao Pham
- Aix Marseille Univ, APHM, University Hospital of Marseille Sainte-Marguerite, Department of Rheumatology, Marseille, France
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12
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Ceban F, Xu J. The Evolution of TNF-α Blockade for the Treatment of Rheumatoid Arthritis. JOURNAL OF UNDERGRADUATE LIFE SCIENCES 2022. [DOI: 10.33137/juls.v16i1.39048] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Tumor necrosis factor (TNF)-α is a potent trimeric cytokine which plays a fundamental role in the host immuno-inflammatory response, as well as in homeostasis and development. Although critical for canonical immune function, TNF-α has great destructive potential and is implicated in the development of multiple immune-mediated disorders. Within the context of rheumatoid arthritis (RA), TNF-α acts as a primary pathogenic driver by precipitating a pro-inflammatory cytokine cascade and coordinating the attraction and activation of immune cells, all of which culminate in damage to the synovium. The discovery of the paramount role of TNF-α in the pathophysiology of RA motivated studies to understand the effects of TNF blockade in vitro and in vivo. Promising preclinical results provided the impetus for clinical trials, spearheaded in the 1980s and 90s by Marc Feldmann, which revealed significant improvements across RA symptom scores and finally led to FDA approval in 1998. As of 2021, five TNF-α blocking agents have been widely applied clinically, including infliximab (IFX), etanercept (ETN), adalimumab (ADA), golimumab (GLM) and certolizumab pegol (CZP). All of them successfully ameliorated symptoms of RA and the associated tissue damage, especially in patients not responding to traditional treatment methods. Anti-TNFs are most often administered in combination with methotrexate (MTX) as part of Phase II treatment (i.e., second line). Although the general availability of anti-TNFs has dramatically improved patient outcomes, sustained remission is rare and the mechanism of RA remains incompletely understood. Thus, additional basic and translational research is warranted, towards the aim of developing novel RA treatments.
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13
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Jain N, Pandey M, Sharma P, Gupta G, Gorain B, Dua K. Recent developments in plant-derived edible nanoparticles as therapeutic nanomedicines. J Food Biochem 2022; 46:e14479. [PMID: 36268842 DOI: 10.1111/jfbc.14479] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2022] [Revised: 09/23/2022] [Accepted: 09/26/2022] [Indexed: 01/14/2023]
Abstract
The use of nanotechnology in the treatment of numerous disorders has proven effective. The predicted development of plant-derived edible nanoparticles (PDNPs) as potential therapeutic agents for treating illness or in the delivery of drugs is inevitable. PDNPs generated from plants resemble mammal-extracted exosomes structurally. In contrast to their excellent biocompatibility with healthy cells, PDNPs are skewed toward malignancies by selectively targeting those cells via unique endocytic pathways. They can be generated in large quantities, are nontoxic, and have tissue-specific targeting abilities. Thus, with fewer off-target effects, using these PDNPs could broaden the breadth of pharmacological therapy. In this discussion, we emphasize the properties and biological activities of PDNPs isolated from fruits and vegetables and discuss the promising implications of these particles as nanomedicines. PRACTICAL APPLICATIONS: PDNPs have reportedly been employed for therapeutic applications for several ailments and are believed to have characteristics in common with exosomes generated from mammals. The advantages of PDNPs over mammalian-derived exosomes are numerous. Firstly, they may be produced on a commercial scale using a variety of efficient renewable sources. Secondly, the PDNPs' natural components developed in plant cells promise improved cytocompatibility, tolerability, low cytotoxicity, or other adverse effects. We evaluated some current studies on the applications and potential of PDNPs in this article. PDNPs could create new opportunities for drug discovery because of recent advancements in medicine and drug delivery system nanotechnology. Unfortunately, the precise mechanisms behind PDNP's functions and interaction in pathogenic processes have not yet been completely elucidated; as a result, the potential consequences of their clinical use are uncertain. Overall, PDNPs show a wide range of therapeutic possibilities that may be advantageous to patients and might eventually make up the next generation of pharmaceuticals.
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Affiliation(s)
- Neha Jain
- Department of Pharmaceutics, Amity Institute of Pharmacy, Amity University, Noida, India
| | - Manisha Pandey
- Department of Pharmaceutical Sciences, Central University of Haryana, Mahendergarh, 123031, India
| | - Palak Sharma
- Department of Pharmaceutics, Amity Institute of Pharmacy, Amity University, Noida, India
| | - Gaurav Gupta
- School of Pharmacy, Suresh Gyan Vihar University, Jaipur, India.,Department of Pharmacology, Saveetha Dental College, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India.,Uttaranchal Institute of Pharmaceutical Sciences, Uttaranchal University, Dehradun, India
| | - Bapi Gorain
- Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi, India
| | - Kamal Dua
- Faculty of Health, Australian Research Centre in Complementary and Integrative Medicine, University of Technology Sydney, Ultimo, New South Wales, 2007, Australia.,Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Ultimo, New South Wales, Australia
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14
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Lima MSR, Gonçalves C, Neto MD, Macedo MH, de Queiroz JLC, da Silva VC, Costa IDS, Camillo CDS, Santos PPDA, Lima AAM, Pastrana L, Maciel BLL, Morais AHA. Anti-Inflammatory Protein Isolated from Tamarind Promotes Better Histological Aspects in the Intestine Regardless of the Improvement of Intestinal Permeability in a Preclinical Study of Diet-Induced Obesity. Nutrients 2022; 14:4669. [PMID: 36364929 PMCID: PMC9655259 DOI: 10.3390/nu14214669] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2022] [Revised: 10/26/2022] [Accepted: 10/28/2022] [Indexed: 11/06/2022] Open
Abstract
Obesity is associated with metabolic and physiological effects in the gut. In this study, we evaluated the anti-inflammatory effect of trypsin inhibitor isolated from tamarind seeds (TTI) in vitro (interaction with lipopolysaccharide (LPS) and inhibitory activity against human neutrophil elastase (HNE)), and using intestinal co-cultures of Caco-2:HT29-MTX cell lines inflamed with TNF-α (50 ng/mL) and a Wistar rat model of diet-induced obesity (n = 15). TTI was administered to animals by gavage (10 days), and the treated group (25 mg/kg/day) was compared to animals without treatment or treated with a nutritionally adequate diet. In the in vitro study, it showed inhibitory activity against HNE (93%). In co-cultures, there was no protection or recovery of the integrity of inflamed cell monolayers treated with TTI (1.0 mg/mL). In animals, TTI led to lower plasma concentrations of TNF-α and IL-6, total leukocytes, fasting glucose, and LDL-c (p < 0.05). The intestines demonstrated a lower degree of chronic enteritis, greater preservation of the submucosa, and greater intestinal wall thickness than the other groups (p = 0.042). Therefore, the better appearance of the intestine not reflected in the intestinal permeability added to the in vitro activity against HNE point to possibilities for new studies and applications related to this activity.
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Affiliation(s)
- Mayara S. R. Lima
- Postgraduate Program in Biochemistry and Molecular Biology, Biosciences Center, Federal University of Rio Grande do Norte, Natal 59075-000, RN, Brazil
| | - Catarina Gonçalves
- International Iberian Nanotechnology Laboratory, 4715-330 Braga, Portugal
| | - Mafalda D. Neto
- International Iberian Nanotechnology Laboratory, 4715-330 Braga, Portugal
| | | | - Jaluza L. C. de Queiroz
- Postgraduate Program in Biochemistry and Molecular Biology, Biosciences Center, Federal University of Rio Grande do Norte, Natal 59075-000, RN, Brazil
| | - Valéria C. da Silva
- Postgraduate Program in Development and Technological Innovation in Medicines, Health Sciences Center, Federal University of Rio Grande do Norte, Natal 59075-000, RN, Brazil
| | - Izael de S. Costa
- Postgraduate Program in Biochemistry and Molecular Biology, Biosciences Center, Federal University of Rio Grande do Norte, Natal 59075-000, RN, Brazil
- Nutrition Course, Potiguar University, Natal 59056-000, RN, Brazil
| | - Christina da S. Camillo
- Department of Morphology, Federal University of Rio Grande do Norte, Natal 59075-000, RN, Brazil
| | - Pedro Paulo de A. Santos
- Department of Morphology, Federal University of Rio Grande do Norte, Natal 59075-000, RN, Brazil
| | - Aldo A. M. Lima
- Department of Physiology and Pharmacology, Federal University of Ceará, Fortaleza 60430-275, CE, Brazil
| | - Lorenzo Pastrana
- International Iberian Nanotechnology Laboratory, 4715-330 Braga, Portugal
| | - Bruna L. L. Maciel
- Postgraduate Program in Nutrition, Health Sciences Center, Federal University of Rio Grande do Norte, Natal 59075-000, RN, Brazil
- Department of Nutrition, Federal University of Rio Grande do Norte, Natal 59075-000, RN, Brazil
| | - Ana Heloneida A. Morais
- Postgraduate Program in Biochemistry and Molecular Biology, Biosciences Center, Federal University of Rio Grande do Norte, Natal 59075-000, RN, Brazil
- Postgraduate Program in Nutrition, Health Sciences Center, Federal University of Rio Grande do Norte, Natal 59075-000, RN, Brazil
- Department of Nutrition, Federal University of Rio Grande do Norte, Natal 59075-000, RN, Brazil
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15
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Advancing Biologic Therapy for Refractory Autoimmune Hepatitis. Dig Dis Sci 2022; 67:4979-5005. [PMID: 35147819 DOI: 10.1007/s10620-021-07378-4] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2021] [Accepted: 12/27/2021] [Indexed: 01/05/2023]
Abstract
Biologic agents may satisfy an unmet clinical need for treatment of refractory autoimmune hepatitis. The goals of this review are to present the types and results of biologic therapy for refractory autoimmune hepatitis, indicate opportunities to improve and expand biologic treatment, and encourage comparative clinical trials. English abstracts were identified in PubMed by multiple search terms. Full-length articles were selected for review, and secondary and tertiary bibliographies were developed. Rituximab (monoclonal antibodies against CD20 on B cells), infliximab (monoclonal antibodies against tumor necrosis factor-alpha), low-dose recombinant interleukin 2 (regulatory T cell promoter), and belimumab (monoclonal antibodies against B cell activating factor) have induced laboratory improvement in small cohorts with refractory autoimmune hepatitis. Ianalumab (monoclonal antibodies against the receptor for B cell activating factor) is in clinical trial. These agents target critical pathogenic pathways, but they may also have serious side effects. Blockade of the B cell activating factor or its receptors may disrupt pivotal B and T cell responses, and recombinant interleukin 2 complexed with certain interleukin 2 antibodies may selectively expand the regulatory T cell population. A proliferation-inducing ligand that enhances T cell proliferation and survival is an unevaluated, potentially pivotal, therapeutic target. Fully human antibodies, expanded target options, improved targeting precision, more effective delivery systems, and biosimilar agents promise to improve efficacy, safety, and accessibility. In conclusion, biologic agents target key pathogenic pathways in autoimmune hepatitis, and early experiences in refractory disease encourage clarification of the preferred target, rigorous clinical trial, and comparative evaluations.
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16
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Proinflammatory cytokines and their receptors as druggable targets to alleviate pathological pain. Pain 2022; 163:S79-S98. [DOI: 10.1097/j.pain.0000000000002737] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2022] [Accepted: 07/14/2022] [Indexed: 02/07/2023]
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17
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Lima MSR, de Lima VCO, Piuvezam G, de Azevedo KPM, Maciel BLL, Morais AHDA. Mechanisms of action of anti-inflammatory proteins and peptides with anti-TNF-alpha activity and their effects on the intestinal barrier: A systematic review. PLoS One 2022; 17:e0270749. [PMID: 35939430 PMCID: PMC9359527 DOI: 10.1371/journal.pone.0270749] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2022] [Accepted: 06/16/2022] [Indexed: 11/30/2022] Open
Abstract
Several studies in animal models of intestinal inflammation have been performed with the aim of understanding the mechanisms of action of anti-inflammatory proteins and peptides that reduce TNF-α. In order to present the best targets, effects and strategies for the treatment of intestinal inflammation in experimental models, this systematic review (SR) aimed to answer the following question: what are the mechanisms of action of molecules with anti-TNF-α activity on the intestinal barrier? The SR protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO, number CRD42019131862) and guided by the methodological procedures used for the elaboration of the SR. Articles that were part of the SR were selected considering the eligibility criteria according to the PICO (Population, Intervention, Comparison/Control and Outcomes) and were searched in the PubMed, Scopus, Web of Science, Excerpta Medica Database (EMBASE) and ScienceDirect databases. Twenty-five articles reporting studies in rats and mice were selected and the risk of bias was assessed using the tool from the SYstematic Review Center for Laboratory Animal Experimentation (SYRCLE). A descriptive synthesis of the results obtained was carried out. Based on the results, the anti-inflammatory molecules that reduced TNF-α acted mainly on the TNF-TNFR1/TNFR2 and TLR4/MD2 complex signaling pathways, and consequently on the NF-κB pathway. This improved the aspects of the inflammatory diseases studied. In addition, these mechanisms also improved the macroscopic, histological and permeability aspects in the intestine of the animals. These findings point to the potential of protein and peptide molecules that act on inflammatory pathways for medical applications with specific and promising strategic targets, aiming to improve inflammatory diseases that affect the intestine. This systematic review also highlights the need for more details during the methodological description of preclinical studies, since this was a limitation found.
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Affiliation(s)
- Mayara Santa Rosa Lima
- Biochemistry and Molecular Biology Postgraduate Program, Biosciences Center, Federal University of Rio Grande do Norte, Natal, RN, Brazil
| | - Vanessa Cristina Oliveira de Lima
- Biochemistry and Molecular Biology Postgraduate Program, Biosciences Center, Federal University of Rio Grande do Norte, Natal, RN, Brazil
| | - Grasiela Piuvezam
- Public Health Postgraduate Program, Center for Health Sciences, Federal University of Rio Grande do Norte, Natal, RN, Brazil
- Department of Public Health, Federal University of Rio Grande do Norte, Natal, RN, Brazil
| | - Kesley Pablo Morais de Azevedo
- Public Health Postgraduate Program, Center for Health Sciences, Federal University of Rio Grande do Norte, Natal, RN, Brazil
| | - Bruna Leal Lima Maciel
- Nutrition Postgraduate Program, Center for Health Sciences, Federal University of Rio Grande do Norte, Natal, RN, Brazil
- Department of Nutrition, Federal University of Rio Grande do Norte, Natal, RN, Brazil
| | - Ana Heloneida de Araújo Morais
- Biochemistry and Molecular Biology Postgraduate Program, Biosciences Center, Federal University of Rio Grande do Norte, Natal, RN, Brazil
- Nutrition Postgraduate Program, Center for Health Sciences, Federal University of Rio Grande do Norte, Natal, RN, Brazil
- Department of Nutrition, Federal University of Rio Grande do Norte, Natal, RN, Brazil
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Hong L, Chen G, Cai Z, Liu H, Zhang C, Wang F, Xiao Z, Zhong J, Wang L, Wang Z, Cui W. Balancing Microthrombosis and Inflammation via Injectable Protein Hydrogel for Inflammatory Bowel Disease. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2022; 9:e2200281. [PMID: 35524641 PMCID: PMC9284187 DOI: 10.1002/advs.202200281] [Citation(s) in RCA: 38] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/15/2022] [Revised: 04/01/2022] [Indexed: 05/17/2023]
Abstract
Emerging evidence indicates that a vicious cycle between inflammation and microthrombosis catalyzes the pathogenesis of inflammatory bowel disease (IBD). Over-stimulated inflammation triggers a coagulation cascade and leads to microthrombosis, which further complicates the injury through tissue hypoxia and ischemia. Herein, an injectable protein hydrogel with anti-thrombosis and anti-inflammation competency is developed to impede this cycle, cross-linked by silver ion mediated metal-ligand coordination and electronic interaction with sulfhydryl functionalized bovine serum albumin and heparin, respectively. The ex vivo experiments show that the hydrogel, HEP-Ag-BSA, exhibits excellent self-healing ability, injectability, biocompatibility, and sustained drug release. HEP-Ag-BSA also demonstrates anti-coagulation and anti-inflammation abilities via coagulation analysis and lipopolysaccharide stimulation assay. The in vivo imaging confirms the longer retention time of HEP-Ag-BSA at inflammatory sites than in normal mucosa owing to electrostatic interactions. The in vivo study applying a mouse model with colitis also reveals that HEP-Ag-BSA can robustly inhibit inflammatory microthrombosis with reduced bleeding risk. This versatile protein hydrogel platform can definitively hinder the "inflammation and microthrombosis" cycle, providing a novel integrated approach against IBD.
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Affiliation(s)
- Liwen Hong
- Department of GastroenterologyRuijin HospitalShanghai Jiao Tong University School of Medicine197 Ruijin 2nd RoadShanghai200025P. R. China
- Department of OrthopaedicsShanghai Key Laboratory for Prevention and Treatment of Bone and Joint DiseasesShanghai Institute of Traumatology and OrthopaedicsRuijin HospitalShanghai Jiao Tong University School of Medicine197 Ruijin 2nd RoadShanghai200025P. R. China
| | - Gaoxian Chen
- Department of Pharmacology and Chemical BiologyInstitute of Molecular MedicineSchool of MedicineShanghai Jiao Tong UniversityShanghai200025P. R. China
| | - Zhengwei Cai
- Department of OrthopaedicsShanghai Key Laboratory for Prevention and Treatment of Bone and Joint DiseasesShanghai Institute of Traumatology and OrthopaedicsRuijin HospitalShanghai Jiao Tong University School of Medicine197 Ruijin 2nd RoadShanghai200025P. R. China
| | - Hua Liu
- Department of GastroenterologyRuijin HospitalShanghai Jiao Tong University School of Medicine197 Ruijin 2nd RoadShanghai200025P. R. China
| | - Chen Zhang
- Department of GastroenterologyRuijin HospitalShanghai Jiao Tong University School of Medicine197 Ruijin 2nd RoadShanghai200025P. R. China
| | - Fei Wang
- Department of OrthopaedicsShanghai Key Laboratory for Prevention and Treatment of Bone and Joint DiseasesShanghai Institute of Traumatology and OrthopaedicsRuijin HospitalShanghai Jiao Tong University School of Medicine197 Ruijin 2nd RoadShanghai200025P. R. China
| | - Zeyu Xiao
- Department of Pharmacology and Chemical BiologyInstitute of Molecular MedicineSchool of MedicineShanghai Jiao Tong UniversityShanghai200025P. R. China
| | - Jie Zhong
- Department of GastroenterologyRuijin HospitalShanghai Jiao Tong University School of Medicine197 Ruijin 2nd RoadShanghai200025P. R. China
| | - Lei Wang
- Department of GastroenterologyRuijin HospitalShanghai Jiao Tong University School of Medicine197 Ruijin 2nd RoadShanghai200025P. R. China
- Department of GeriatricsRuijin HospitalShanghai Jiao Tong University School of Medicine197 Ruijin 2nd RoadShanghai200025P. R. China
| | - Zhengting Wang
- Department of GastroenterologyRuijin HospitalShanghai Jiao Tong University School of Medicine197 Ruijin 2nd RoadShanghai200025P. R. China
| | - Wenguo Cui
- Department of OrthopaedicsShanghai Key Laboratory for Prevention and Treatment of Bone and Joint DiseasesShanghai Institute of Traumatology and OrthopaedicsRuijin HospitalShanghai Jiao Tong University School of Medicine197 Ruijin 2nd RoadShanghai200025P. R. China
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19
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González-Ballesteros N, Diego-González L, Lastra-Valdor M, Grimaldi M, Cavazza A, Bigi F, Rodríguez-Argüelles MC, Simón-Vázquez R. Immunomodulatory and Antitumoral Activity of Gold Nanoparticles Synthesized by Red Algae Aqueous Extracts. Mar Drugs 2022; 20:md20030182. [PMID: 35323481 PMCID: PMC8953345 DOI: 10.3390/md20030182] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2022] [Revised: 02/21/2022] [Accepted: 02/24/2022] [Indexed: 12/11/2022] Open
Abstract
This study reports on the green and cost-efficient synthesis of gold nanoparticles from three different red algae extracts. The nanoparticles synthesized were fully characterized by UV-Vis spectroscopy, HRTEM, and Z-potential. Relevant components occurring in the extracts, such as polysaccharides or phenolic content, were assessed by analytical techniques such as spectrophotometric assays and liquid chromatography. Finally, the antioxidant, antitumoral, and anti-inflammatory potential of both the extracts and the gold nanoparticles synthesized were analyzed in order to determine a possible synergistic effect on the nanoparticles. The results obtained confirmed the obtainment of gold nanoparticles with significant potential as immunotherapeutic agents. The therapeutic potential of these nanoparticles could be higher than that of inert gold nanoparticles loaded with bioactive molecules since the former would allow for higher accumulation into the targeted tissue.
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Affiliation(s)
| | - Lara Diego-González
- CINBIO, Immunology Group, Universidade de Vigo, 36310 Vigo, Spain; (L.D.-G.); (R.S.-V.)
- Instituto de Investigación Sanitaria Galicia Sur, Hospital Alvaro Cunqueiro, 36312 Vigo, Spain
| | | | - Maria Grimaldi
- Dipartimento Scienze Chimiche, della Vita e della Sostenibilità Ambientale, Università di Parma, 43124 Parma, Italy; (M.G.); (A.C.); (F.B.)
| | - Antonella Cavazza
- Dipartimento Scienze Chimiche, della Vita e della Sostenibilità Ambientale, Università di Parma, 43124 Parma, Italy; (M.G.); (A.C.); (F.B.)
| | - Franca Bigi
- Dipartimento Scienze Chimiche, della Vita e della Sostenibilità Ambientale, Università di Parma, 43124 Parma, Italy; (M.G.); (A.C.); (F.B.)
- Institute of Materials for Electronics and Magnetism, National Research Council, 43124 Parma, Italy
| | | | - Rosana Simón-Vázquez
- CINBIO, Immunology Group, Universidade de Vigo, 36310 Vigo, Spain; (L.D.-G.); (R.S.-V.)
- Instituto de Investigación Sanitaria Galicia Sur, Hospital Alvaro Cunqueiro, 36312 Vigo, Spain
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20
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Nguyen TK, Niaz Z, Kruzel ML, Actor JK. Recombinant Human Lactoferrin Reduces Inflammation and Increases Fluoroquinolone Penetration to Primary Granulomas During Mycobacterial Infection of C57Bl/6 Mice. Arch Immunol Ther Exp (Warsz) 2022; 70:9. [PMID: 35226195 PMCID: PMC8922470 DOI: 10.1007/s00005-022-00648-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2021] [Accepted: 11/18/2021] [Indexed: 12/15/2022]
Abstract
Infection with Mycobacterium tuberculosis (Mtb) results in the primary formation of a densely packed inflammatory foci that limits entry of therapeutic agents into pulmonary sites where organisms reside. No current therapeutic regimens exist that modulate host immune responses to permit increased drug penetration to regions of pathological damage during tuberculosis disease. Lactoferrin is a natural iron-binding protein previously demonstrated to modulate inflammation and granuloma cohesiveness, while maintaining control of pathogenic burden. Studies were designed to examine recombinant human lactoferrin (rHLF) to modulate histological progression of Mtb-induced pathology in a non-necrotic model using C57Bl/6 mice. The rHLF was oral administered at times corresponding to initiation of primary granulomatous response, or during granuloma maintenance. Treatment with rHLF demonstrated significant reduction in size of primary inflammatory foci following Mtb challenge, and permitted penetration of ofloxacin fluoroquinolone therapeutic to sites of pathological disruption where activated (foamy) macrophages reside. Increased drug penetration was accompanied by retention of endothelial cell integrity. Immunohistochemistry revealed altered patterns of M1-like and M2-like phenotypic cell localization post infectious challenge, with increased presence of M2-like markers found evenly distributed throughout regions of pulmonary inflammatory foci in rHLF-treated mice.
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Affiliation(s)
- Thao K.T. Nguyen
- Department of Pathology and Laboratory Medicine, UTHealth McGovern Medical School, Houston, TX, USA,The University of Texas MD Anderson Cancer Center – UTHealth Graduate School of Biomedical Sciences, Houston, TX 77030, USA
| | - Zainab Niaz
- Department of Pathology and Laboratory Medicine, UTHealth McGovern Medical School, Houston, TX, USA
| | - Marian L. Kruzel
- Department of Pathology and Laboratory Medicine, UTHealth McGovern Medical School, Houston, TX, USA
| | - Jeffrey K. Actor
- Department of Pathology and Laboratory Medicine, UTHealth McGovern Medical School, Houston, TX, USA
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21
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Interactions between human milk oligosaccharides, microbiota and immune factors in milk of women with and without mastitis. Sci Rep 2022; 12:1367. [PMID: 35079053 PMCID: PMC8789856 DOI: 10.1038/s41598-022-05250-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2021] [Accepted: 12/20/2021] [Indexed: 12/21/2022] Open
Abstract
Lactational mastitis is an excellent target to study possible interactions between HMOs, immune factors and milk microbiota due to the infectious and inflammatory nature of this condition. In this work, microbiological, immunological and HMO profiles of milk samples from women with (MW) or without (HW) mastitis were compared. Secretor status in women (based on HMO profile) was not associated to mastitis. DFLNH, LNFP II and LSTb concentrations in milk were higher in samples from HW than from MW among Secretor women. Milk from HW was characterized by a low bacterial load (dominated by Staphylococcus epidermidis and streptococci), high prevalence of IL10 and IL13, and low sialylated HMO concentration. In contrast, high levels of staphylococci, streptococci, IFNγ and IL12 characterized milk from MW. A comparison between subacute (SAM) and acute (AM) mastitis cases revealed differences related to the etiological agent (S. epidermidis in SAM; Staphylococcus aureus in AM), milk immunological profile (high content of IL10 and IL13 in SAM and IL2 in AM) and milk HMOs profile (high content of 3FL in SAM and of LNT, LNnT, and LSTc in AM). These results suggest that microbiological, immunological and HMOs profiles of milk are related to mammary health of women.
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22
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Feng Y, Zhou B, Wang Z, Xu G, Wang L, Zhang T, Zhang Y. Risk of Candida Infection and Serious Infections in Patients with Moderate-to-Severe Psoriasis Receiving Biologics: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Int J Clin Pract 2022; 2022:2442603. [PMID: 36212052 PMCID: PMC9519312 DOI: 10.1155/2022/2442603] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2022] [Accepted: 09/05/2022] [Indexed: 11/17/2022] Open
Abstract
BACKGROUND Biological agents used to treat moderate-to-severe plaque psoriasis have been associated with Candida infection and other serious infections. It is, however, necessary to verify whether biologic agents increase the risk of Candida infection and serious infections and whether these risks vary among biologics. METHODS PubMed, EMBASE, and Cochrane Library were searched for eligible randomized controlled trials (RCTs) from their inception to December 2021. Results from individual RCT were pooled using Peto's method with a fixed-effects model, and I 2 was calculated to assess the heterogeneity. A Cochrane collaboration tool was used to examine bias risk, and Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) were used to assess the quality of evidence. RESULTS This study included 48 published articles with data from 52 RCTs involving 27297 participants. The anti-interleukin (IL)-17 agents (95% confidence interval (CI) = 1.54-3.45, P < 0.0001) and anti-IL-12/23 agents (95% CI = 1.69-3.83, P < 0.0001) were associated with an increased risk of Candida infection compared with placebos, but there was no difference in Candida infection risk between anti-IL-17 agents and tumor necrosis factor inhibitors (TNFi) (95% CI = 0.92-3.07, P=0.09). There was no evidence that the biological agents increased the risk of serious infections in adult psoriasis (95% CI = 0.93-2.06, P=0.11) or that the biologics differed in the risk of serious infections. CONCLUSIONS Our results indicated that anti-IL-17 agents, especially secukinumab, were associated with the increased risk of Candida infection. The clinically used biological agents did not increase the risk of serious infections.
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Affiliation(s)
- Yue Feng
- Department of Dermatology, Shenyang Seventh People's Hospital, Shenyang 110001, Liaoning, China
| | - Baosen Zhou
- Department of Epidemiology, School of Public Health, China Medical University, Shenyang 110001, Liaoning, China
| | - Zhen Wang
- Department of Dermatology, Shenyang Seventh People's Hospital, Shenyang 110001, Liaoning, China
| | - Guijuan Xu
- Department of Dermatology, Shenyang Seventh People's Hospital, Shenyang 110001, Liaoning, China
| | - Lili Wang
- Department of Dermatology, Shenyang Seventh People's Hospital, Shenyang 110001, Liaoning, China
| | - Tingting Zhang
- Department of Dermatology, Shenyang Seventh People's Hospital, Shenyang 110001, Liaoning, China
| | - Yanping Zhang
- Department of Dermatology, Shenyang Seventh People's Hospital, Shenyang 110001, Liaoning, China
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23
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Fernández-Ruiz M. Interleukin-12 and -23 Targeted Agents. INFECTIOUS COMPLICATIONS IN BIOLOGIC AND TARGETED THERAPIES 2022:199-217. [DOI: 10.1007/978-3-031-11363-5_11] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/02/2023]
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24
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Fortea M, Albert-Bayo M, Abril-Gil M, Ganda Mall JP, Serra-Ruiz X, Henao-Paez A, Expósito E, González-Castro AM, Guagnozzi D, Lobo B, Alonso-Cotoner C, Santos J. Present and Future Therapeutic Approaches to Barrier Dysfunction. Front Nutr 2021; 8:718093. [PMID: 34778332 PMCID: PMC8582318 DOI: 10.3389/fnut.2021.718093] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Accepted: 09/29/2021] [Indexed: 12/12/2022] Open
Abstract
There is converging and increasing evidence, but also uncertainty, for the role of abnormal intestinal epithelial barrier function in the origin and development of a growing number of human gastrointestinal and extraintestinal inflammatory disorders, and their related complaints. Despite a vast literature addressing factors and mechanisms underlying changes in intestinal permeability in humans, and its connection to the appearance and severity of clinical symptoms, the ultimate link remains to be established in many cases. Accordingly, there are no directives or clinical guidelines related to the therapeutic management of intestinal permeability disorders that allow health professionals involved in the management of these patients to carry out a consensus treatment based on clinical evidence. Instead, there are multiple pseudoscientific approaches and commercial propaganda scattered on the internet that confuse those affected and health professionals and that often lack scientific rigor. Therefore, in this review we aim to shed light on the different therapeutic options, which include, among others, dietary management, nutraceuticals and medical devices, microbiota and drugs, and epigenetic and exosomes-manipulation, through an objective evaluation of the scientific publications in this field. Advances in the knowledge and management of intestinal permeability will sure enable better options of dealing with this group of common disorders to enhance quality of life of those affected.
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Affiliation(s)
- Marina Fortea
- Laboratory for Enteric NeuroScience, Translational Research Center for GastroIntestinal Disorders, University of Leuven, Leuven, Belgium
| | - Mercé Albert-Bayo
- Laboratory of Neuro-Immuno-Gastroenterology, Digestive System Research Unit, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Barcelona, Spain
| | - Mar Abril-Gil
- Laboratory of Neuro-Immuno-Gastroenterology, Digestive System Research Unit, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Barcelona, Spain
| | - John-Peter Ganda Mall
- Laboratory of Neuro-Immuno-Gastroenterology, Digestive System Research Unit, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Barcelona, Spain
- Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden
| | - Xavier Serra-Ruiz
- Department of Gastroenterology, Vall d'Hebron Hospital Universitari, Barcelona, Spain
| | - Alejandro Henao-Paez
- Department of Gastroenterology, Vall d'Hebron Hospital Universitari, Barcelona, Spain
| | - Elba Expósito
- Laboratory of Neuro-Immuno-Gastroenterology, Digestive System Research Unit, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Barcelona, Spain
| | - Ana María González-Castro
- Laboratory of Neuro-Immuno-Gastroenterology, Digestive System Research Unit, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Barcelona, Spain
| | - Danila Guagnozzi
- Laboratory of Neuro-Immuno-Gastroenterology, Digestive System Research Unit, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Barcelona, Spain
- Department of Gastroenterology, Vall d'Hebron Hospital Universitari, Barcelona, Spain
- Facultad de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERHED), Instituto de Salud Carlos III, Madrid, Spain
| | - Beatriz Lobo
- Laboratory of Neuro-Immuno-Gastroenterology, Digestive System Research Unit, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Barcelona, Spain
- Department of Gastroenterology, Vall d'Hebron Hospital Universitari, Barcelona, Spain
- Facultad de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain
| | - Carmen Alonso-Cotoner
- Laboratory of Neuro-Immuno-Gastroenterology, Digestive System Research Unit, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Barcelona, Spain
- Department of Gastroenterology, Vall d'Hebron Hospital Universitari, Barcelona, Spain
- Facultad de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERHED), Instituto de Salud Carlos III, Madrid, Spain
| | - Javier Santos
- Laboratory of Neuro-Immuno-Gastroenterology, Digestive System Research Unit, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Barcelona, Spain
- Department of Gastroenterology, Vall d'Hebron Hospital Universitari, Barcelona, Spain
- Facultad de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERHED), Instituto de Salud Carlos III, Madrid, Spain
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Ren D, Wu D, Liu F, Jiao S, Wu Y. Diagnostic value of heparin-binding protein in the cerebrospinal fluid for purulent meningitis in children. ACTA ACUST UNITED AC 2021; 54:e11295. [PMID: 34495248 PMCID: PMC8427748 DOI: 10.1590/1414-431x2021e11295] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2021] [Accepted: 06/07/2021] [Indexed: 11/21/2022]
Abstract
This study aimed to investigate the diagnostic value of heparin-binding protein (HBP) in the cerebrospinal fluid of children with purulent meningitis (PM). This study included 118 children with PM diagnosed at our hospital from January 2018 to January 2020, 110 children with viral meningitis (VM) and 80 children with suspected meningitis who were ruled out by cerebrospinal fluid (CSF) analysis during the same period. HBP and white blood cell (WBC) count in the CSF, and inflammatory factors, including C-reactive protein (CRP), tumor necrosis factor (TNF)-α, and procalcitonin (PCT), were measured. Receiver-operator characteristic curves were used to analyze the predictive value of HBP, CRP, PCT, and TNF-α levels in the diagnosis of PM by CSF analysis. HBP levels in the CSF of children with PM were higher, while the CRP and serum PCT and TNF-α levels were elevated in all groups (P<0.05). In addition, HBP levels in the CSF were more accurate for the diagnosis of PM than traditional diagnostic indexes. HBP levels in the CSF can be used as an important reference for early diagnosis of PM.
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Affiliation(s)
- Dan Ren
- Department of Pediatrics, Mianyang Central Hospital, Mianyang, Sichuan, China
| | - Di Wu
- Department of Gynecology and Pediatrics, Hospital of PLA Unit 63820, Mianyang, Sichuan, China
| | - Fu Liu
- Department of Pediatrics, Mianyang Central Hospital, Mianyang, Sichuan, China
| | - Shuli Jiao
- Department of Pediatrics, Mianyang Central Hospital, Mianyang, Sichuan, China
| | - Yi Wu
- Department of Pediatrics, Mianyang Central Hospital, Mianyang, Sichuan, China
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26
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de Souza MM, Chagas LGRD, Gonçalves AE, Tomczak M, Reichert S, Schuquel ITA, Cechinel-Filho V, Meyre-Silva C. Phytochemical Analysis and Antinociceptive Properties of Hydroalcoholic Extracts of Aleurites moluccanus Bark. PLANTA MEDICA 2021; 87:896-906. [PMID: 34034350 DOI: 10.1055/a-1497-0239] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/12/2023]
Abstract
Aleurites moluccanus is used in folk medicine to treat many diseases including pain and inflammatory processes in general. Considering the potential of the leaf extract, evidenced in a previous study, the present study investigates the antinociceptive and anti-inflammatory properties of the hydroethanolic extract of A. moluccanus bark and isolated compounds in animal models of pain. The antinociceptive and anti-inflammatory activities of A. moluccanus bark were evaluated through hyperalgesia induced by carrageenan, PGE2, cytokines, bradykinin, epinephrine, Freund's complete adjuvant, and lipopolysaccharide. Five compounds were isolated from the dichloromethane bark extract: acetyl aleuritolic acid, atraric acid, spruceanol, (5β,10α)-12-hydroxy-13-methoxy-8,11,13-podocarpatrien-3-one and sonderianol. To optimize the extraction conditions, ethanol 50, 70, and 90°GL were used as extracting solvent, in a 1 : 20 (w/v) drug : solvent ratio, under stirring at room temperature for 4 h. The extracts were named AMC50, AMC70, and AMC90, respectively. These extracts were administered to mice (250 mg/kg, p. o.) with reduced mechanical hyperalgesia activity in the carrageenan test. Of these, AMC90 showed the best results. Pure (5β,10α)-12-hydroxy-13-methoxy-8,11,13-podocarpatrien-3-one showed a beneficial effect for up to 48 hours after the administration of carrageenan, while acetyl aleuritolic acid was effective only in the first hour. AMC90 was able to reverse the analgesia induced only by prostaglandin E2 and tumor necrosis factor. We also induced hyperalgesia using the lipopolysaccharide and Freund's complete adjuvant models, with positive results. These results support the antinociceptive and anti-inflammatory activity of A. moluccanus bark extract. The observed effects are partly due to the presence of acetyl aleuritolic acid, atraric acid, and (5β,10α)-12-hydroxy-13-methoxy-8,11,13-podocarpatrien-3-one.
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Affiliation(s)
- Márcia Maria de Souza
- Universidade do Vale do Itajaí (UNIVALI), Escola de Ciências da Saúde, Itajaí, Santa Catarina State, Brazil
| | - Luiz G R D Chagas
- Universidade do Vale do Itajaí (UNIVALI), Escola de Ciências da Saúde, Itajaí, Santa Catarina State, Brazil
| | - Ana Elisa Gonçalves
- Universidade do Vale do Itajaí (UNIVALI), Escola de Ciências da Saúde, Itajaí, Santa Catarina State, Brazil
| | - Marcelo Tomczak
- Universidade do Vale do Itajaí (UNIVALI), Escola de Ciências da Saúde, Itajaí, Santa Catarina State, Brazil
| | - Simone Reichert
- Universidade do Vale do Itajaí (UNIVALI), Escola de Ciências da Saúde, Itajaí, Santa Catarina State, Brazil
| | - Ivania T A Schuquel
- Universidade Estadual de Maringá (UEM), Departamento de Química, Maringá, Paraná State, Brazil
| | - Valdir Cechinel-Filho
- Universidade do Vale do Itajaí (UNIVALI), Escola de Ciências da Saúde, Itajaí, Santa Catarina State, Brazil
| | - Christiane Meyre-Silva
- Pós-graduação em Farmácia. Universidade Federal de Santa Catarina (UFSC), Bloco JK, Campus Reitor João David Ferreira Lima, Trindade, Florianópolis, Santa Catarina State, Brazil
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Hamamoto Filho PT, Fragoso G, Sciutto E, Fleury A. Inflammation in neurocysticercosis: clinical relevance and impact on treatment decisions. Expert Rev Anti Infect Ther 2021; 19:1503-1518. [PMID: 33794119 DOI: 10.1080/14787210.2021.1912592] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
INTRODUCTION Neurocysticercosis is caused by the localization of Taenia solium larvae in the central nervous system. The disease remains endemic in most countries of Latin America, Asia and Africa. While major improvements have been made in its diagnosis and treatment, uncertainties persist regarding the clinical implications and treatment of the inflammatory reaction associated with the disease. AREAS COVERED In this review, based on PubMed searches, the authors describe the characteristics of the immune-inflammatory response in patients with neurocysticercosis, its clinical implications and the treatment currently administered. The dual role of inflammation (participating in both, the death of the parasite, and the precipitation of serious complications) is discussed. New therapeutic strategies of potential interest are presented. EXPERT OPINION Inflammatory reaction is the main pathogenic mechanism associated to neurocysticercosis. Its management is mainly based on corticosteroids administration. This strategy had improved prognostic of patients as it allows for the control of most of the inflammatory complications. On the other side, it might be involved in the persistence of parasites in some patients, despite cysticidal treatment, due to its immunosuppressive properties. New strategies are needed to improve therapeutical management, particularly in the severest presentations.
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Affiliation(s)
- Pedro T Hamamoto Filho
- Department of Neurology, Psychology and Psychiatry, UNESP-Univ Estadual Paulista, Botucatu Medical School, Botucatu, Brazil
| | - Gladis Fragoso
- Department of Immunology, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad de México, Mexico
| | - Edda Sciutto
- Department of Immunology, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad de México, Mexico
| | - Agnès Fleury
- Department of Genomic Medicine and Environmental Toxicology, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad de México, Mexico.,Neurocysticercosis Clinic, Instituto Nacional de Neurología Y Neurocirugía, Ciudad de México, Mexico, mexico.,Neuroinflammation Unit, Instituto de Investigaciones Biomédicas-Universidad Nacional Autónoma de México/INNN/Facultad de Medicina-UNAM, Ciudad de México, Mexico
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Zhu Q, Wang J, Ma J, Sheng X, Li F. Changes in inflammatory factors in the Brown Norway rat model of food allergy. BMC Immunol 2021; 22:8. [PMID: 33499808 PMCID: PMC7839196 DOI: 10.1186/s12865-021-00398-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2020] [Accepted: 01/05/2021] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND The role of serum S100A8/A9 in intestinal inflammation has been confirmed, and its role in food allergy is currently being investigated. OBJECTIVE To explore the levels of S100A8/A9 and inflammatory factors, including Toll-like receptors 4 (TLR4), Nuclear transcription factors (NF-κB) and Tumor necrosis factor α (TNF-α), in mild food allergies. METHODS Eighty 3-week-old male Brown Norway rats were used. Forty rats were randomly assigned to the ovalbumin-sensitized experimental group, while 40 rats were assigned to the normal saline sham-sensitized control group. Body weight and length and the levels of serum ovalbumin-specific IgE (OVA-IgE), histamine, Th1-associated and Th2-associated factors, S100A8/A9 and inflammation-associated cytokines were compared. RESULTS Through the evaluation of OVA-IgE level and Th1/Th2 balance in the experimental group, a successful IgE-mediated food allergy model was constructed. Compared with the control group, the experimental group had higher serum S100A8/A9 levels on days 21, 28, 35 and 42 (all P < 0.05); higher TLR4 levels on days 28, 35 and 42 (all P < 0.05); higher TNF-α levels on days 28, 35 and 42 (all P < 0.05); higher NF-κB levels on days 35 and 42 (all P < 0.05); and higher IL-1β and IL-6 levels on days 7 to 42 (all P < 0.05). Moreover, positive correlations were found between the serum levels of S100A8/A9 and inflammation-associated cytokines [TNF-α: r = 0.378, P = 0.039; IL-1β: r = 0.679, P = 0.000; IL-6: r = 0.590, P = 0.001]. CONCLUSION S100A8/A9 and inflammatory-related factors, including TLR4, NF-κB, TNF-α, IL-6 and IL-1β, is closely related to food allergies. Moreover, immune and inflammatory factors interact with each other in food allergies, which may provide insight into food allergy causes and treatments.
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Affiliation(s)
- Qingling Zhu
- Department of Child and Adolescent Healthcare, MOE-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, No. 1665 Kongjiang Road, Yangpu Shanghai, 200092, China.,Department of Children Healthcare, Quanzhou Women's and Children's Hospital, Quanzhou, 362000, Fujian, China
| | - Junli Wang
- Department of Child and Adolescent Healthcare, MOE-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, No. 1665 Kongjiang Road, Yangpu Shanghai, 200092, China
| | - Jingqiu Ma
- Department of Child and Adolescent Healthcare, MOE-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, No. 1665 Kongjiang Road, Yangpu Shanghai, 200092, China
| | - Xiaoyang Sheng
- Department of Child and Adolescent Healthcare, MOE-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, No. 1665 Kongjiang Road, Yangpu Shanghai, 200092, China.
| | - Feng Li
- Department of Child and Adolescent Healthcare, MOE-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, No. 1665 Kongjiang Road, Yangpu Shanghai, 200092, China.
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Fang H, Yu L, You D, Peng N, Guo W, Wang J, Zhang X. In vivo Therapeutic Effects and Mechanisms of Hydroxyasiaticoside Combined With Praziquantel in the Treatment of Schistosomiasis Induced Hepatic Fibrosis. Front Bioeng Biotechnol 2021; 8:613784. [PMID: 33553120 PMCID: PMC7862569 DOI: 10.3389/fbioe.2020.613784] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2020] [Accepted: 12/10/2020] [Indexed: 12/12/2022] Open
Abstract
Schistosomiasis has been a fatal obstinate disease that threatens global human health, resulting in the granulomatous inflammation and liver fibrosis. Objective:The aim of this study was to evaluate the therapeutic effects and mechanisms of hydroxyasiaticoside combined with praziquantel in the treatment of schistosomiasis-induced liver fibrosis. Methods:Mice were randomly distributed into four experimental groups: normal control group, model group, praziquantel group, praziquantel + hydroxyasiaticoside group. Except for the normal control group, they were infected with Schistosomia cercariae through the abdominal skin to induce liver fibrosis. In the intervention group, mice were administered with the respective drugs by gavage after 8 weeks of infection. At the end of the treatment, mice were sacrificed to collect blood for the determination of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) serum levels. Moreover, the liver was excised, weighed, and liver indices were calculated. Histopathological examination was performed to assess liver morphology. Besides, the expression of collagen type I and III in liver was determined; the mRNA expression levels of IL-6 and TNF-α in liver tissues were measured using Real-time PCR while ELISA and western blotting were performed on liver tissue homogenate to determine the protein expression of IL-6 and TNF-α. Results:The combination of praziquantel and hydroxyasiaticoside lowered the pathological scores of schistosomiasis-induced hepatic fibrosis, the liver indice, serum AST and ALT levels, improved liver morphology, downregulated the expression levels of hepatic type I and III collagen, inhibited the mRNA expression levels of pro-inflammatory factors (IL-6 and TNF-α) in the liver of mice relative to the praziquantel alone. Conclusion:The combination of hydroxyasiaticoside and praziquantel is a potential therapeutic option for schistosomiasis-induced hepatic fibrosis. Notably, this combination noticeably suppresses the protein and mRNA expression levels of pro-inflammatory factors (TNF-α and IL-6) in the liver.
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Affiliation(s)
- Huilong Fang
- Department of Pharmacology, Xiangnan University, Chenzhou, China
| | - Ling Yu
- Affiliated Hospital of Xiangnan University, Chenzhou, China
| | - Da You
- Department of Pharmacology, Xiangnan University, Chenzhou, China
| | - Nan Peng
- Department of Pharmacology, Xiangnan University, Chenzhou, China
| | - Wanbei Guo
- Department of Pharmacology, Xiangnan University, Chenzhou, China
| | - Junjie Wang
- Department of Pharmacology, Xiangnan University, Chenzhou, China
| | - Xing Zhang
- Department of Trauma and Reconstructive Surgery, Rheinisch-Westfälische Technische Hochschule Aachen University Hospital, Aachen, Germany
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José da Silva R, da Rocha Ribeiro TC, Chebli LA, Chebli JMF. An Unexpected Cause of Headache and Splenic Lesions During Anti-TNF Therapy in Crohn Disease. Inflamm Bowel Dis 2021; 27:e1-e2. [PMID: 32812018 DOI: 10.1093/ibd/izaa226] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Affiliation(s)
- Raphael José da Silva
- From the Division of Gastroenterology, Inflammatory Bowel Diseases Center, University Hospital of the Federal University of Juiz de Fora, University of Juiz de Fora School of Medicine, Minas Gerais, Brazil
| | - Tarsila Campanha da Rocha Ribeiro
- From the Division of Gastroenterology, Inflammatory Bowel Diseases Center, University Hospital of the Federal University of Juiz de Fora, University of Juiz de Fora School of Medicine, Minas Gerais, Brazil
| | - Liliana Andrade Chebli
- From the Division of Gastroenterology, Inflammatory Bowel Diseases Center, University Hospital of the Federal University of Juiz de Fora, University of Juiz de Fora School of Medicine, Minas Gerais, Brazil
| | - Julio Maria Fonseca Chebli
- From the Division of Gastroenterology, Inflammatory Bowel Diseases Center, University Hospital of the Federal University of Juiz de Fora, University of Juiz de Fora School of Medicine, Minas Gerais, Brazil
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Ciccocioppo R, Comoli P, Astori G, Del Bufalo F, Prapa M, Dominici M, Locatelli F. Developing cell therapies as drug products. Br J Pharmacol 2020; 178:262-279. [PMID: 33140850 DOI: 10.1111/bph.15305] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2020] [Revised: 10/22/2020] [Accepted: 10/23/2020] [Indexed: 02/06/2023] Open
Abstract
In the last 20 years, the global regulatory frameworks for drug assessment have been managing the challenges posed by using cellular products as new therapeutic tools. Currently, they are defined as "Advanced Therapy Medicinal Products", comprising a large group of cellular types that either alone or in combination with gene and tissue engineering technology. They have the potential to change the natural course of still lethal or highly debilitating diseases, including cancers, opportunistic infections and chronic inflammatory conditions. Globally, more than 50 cell-based products have obtained market authorization. This overview describes the advantages and unsolved challenges on developing cells as innovative therapeutic vehicles. The main cell therapy players and the legal framework are discussed, starting from chimeric antigen receptor T-cells for leukaemia and solid tumours, dealing then with lymphocytes as potent anti-microbiological tools and then focusing on mesenchymal stem/stromal cells whose role covers regenerative medicine, immunology and anti-tumour therapy.
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Affiliation(s)
- Rachele Ciccocioppo
- Gastroenterology Unit, Department of Medicine, A.O.U.I. Policlinico G.B. Rossi & University of Verona, Verona, Italy
| | - Patrizia Comoli
- Cell Factory and Paediatric Haematology/Oncology Unit, Fondazione I.R.C.C.S. Policlinico San Matteo, Pavia, Italy
| | - Giuseppe Astori
- Laboratory of Advanced Cellular Therapies, Haematology Unit, San Bortolo Hospital, A.U.L.S.S. 8 "Berica", Vicenza, Italy
| | - Francesca Del Bufalo
- Department of Paediatric Haematology and Oncology and Cell and Gene Therapy, I.R.C.C.S. Bambino Gesù Children's Hospital, Rome, Italy
| | - Malvina Prapa
- Division of Oncology, Department of Medical and Surgical Sciences for Children & Adults, University of Modena and Reggio Emilia, Modena, Italy
| | - Massimo Dominici
- Division of Oncology, Department of Medical and Surgical Sciences for Children & Adults, University of Modena and Reggio Emilia, Modena, Italy
| | - Franco Locatelli
- Department of Paediatric Haematology and Oncology and Cell and Gene Therapy, I.R.C.C.S. Bambino Gesù Children's Hospital, Rome, Italy.,Department of Paediatrics, Sapienza University of Rome, Rome, Italy
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Fougerousse AC. Utilisation d’une biothérapie pour du psoriasis chez un patient atteint de syndrome de Cohen. Ann Dermatol Venereol 2020; 147:880-881. [DOI: 10.1016/j.annder.2020.07.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2020] [Revised: 03/23/2020] [Accepted: 07/06/2020] [Indexed: 10/23/2022]
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Shannon VR, Anderson R, Blidner A, Choi J, Cooksley T, Dougan M, Glezerman I, Ginex P, Girotra M, Gupta D, Johnson DB, Suarez-Almazor ME, Rapoport BL. Multinational Association of Supportive Care in Cancer (MASCC) 2020 clinical practice recommendations for the management of immune-related adverse events: pulmonary toxicity. Support Care Cancer 2020; 28:6145-6157. [PMID: 32880733 PMCID: PMC7471521 DOI: 10.1007/s00520-020-05708-2] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2020] [Accepted: 08/20/2020] [Indexed: 12/15/2022]
Abstract
The immune checkpoints associated with the CTLA-4 and PD-1 pathways are critical modulators of immune activation. These pathways dampen the immune response by providing brakes on activated T cells, thereby ensuring more uniform and controlled immune reactions and avoiding immune hyper-responsiveness and autoimmunity. Cancer cells often exploit these regulatory controls through a variety of immune subversion mechanisms, which facilitate immune escape and tumor survival. Immune checkpoint inhibitors (ICI) effectively block negative regulatory signals, thereby augmenting immune attack and tumor killing. This process is a double-edged sword in which release of regulatory controls is felt to be responsible for both the therapeutic efficacy of ICI therapy and the driver of immune-related adverse events (IrAEs). These adverse immune reactions are common, typically low-grade and may affect virtually every organ system. In the early clinical trials, lung IrAEs were rarely described. However, with ever-expanding clinical applications and more complex ICI-containing regimens, lung events, in particular, pneumonitis, have become increasingly recognized. ICI-related lung injury is clinically distinct from other types of lung toxicity and may lead to death in advanced stage disease. Thus, knowledge regarding the key characteristics and optimal treatment of lung-IrAEs is critical to good outcomes. This review provides an overview of lung-IrAEs, including risk factors and epidemiology, as well as clinical, radiologic, and histopathologic features of ICI-related lung injury. Management principles for ICI-related lung injury, including current consensus on steroid refractory pneumonitis and the use of other immune modulating agents in this setting are also highlighted.
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Affiliation(s)
- Vickie R. Shannon
- Department of Pulmonary Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX USA
| | - Ronald Anderson
- Department of Immunology, Faculty of Health Sciences, University or Pretoria, Corner Doctor Savage Road and Bophelo Road, Pretoria, 0002 South Africa
| | - Ada Blidner
- Laboratory of Immunopathology, Institute of Biology and Experimental Medicine-CONICET, Buenos Aires, Argentina
| | - Jennifer Choi
- Division of Oncodermatology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL USA
| | - Tim Cooksley
- Manchester University Foundation Trust, Manchester, UK
- The Christie, University of Manchester, Manchester, UK
| | - Michael Dougan
- Massachusetts General Hospital, Boston, MA USA
- Harvard Medical School, Boston, MA USA
| | - Ilya Glezerman
- Renal Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY USA
| | | | - Monica Girotra
- Endocrine Division, Department of Medicine, Weill Cornell Medical College (MG, AF), New York, NY USA
- Department of Medicine (DJB), Memorial Sloan-Kettering Cancer Center (MC), New York, NY USA
| | - Dipti Gupta
- Department of Medicine (DJB), Memorial Sloan-Kettering Cancer Center (MC), New York, NY USA
| | - Douglas B. Johnson
- Department of Medicine, Vanderbilt University Medical Center and Vanderbilt Ingram Cancer Center, Nashville, TN USA
| | - Maria E. Suarez-Almazor
- Section of Rheumatology and Clinical Immunology, University of Texas MD Anderson Cancer Center, Houston, USA
| | - Bernardo L. Rapoport
- Department of Immunology, Faculty of Health Sciences, University or Pretoria, Corner Doctor Savage Road and Bophelo Road, Pretoria, 0002 South Africa
- The Medical Oncology Centre of Rosebank, 129 Oxford Road, Saxonwold, Johannesburg, 2196 South Africa
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Teixeira-Santos L, Albino-Teixeira A, Pinho D. Neuroinflammation, oxidative stress and their interplay in neuropathic pain: Focus on specialized pro-resolving mediators and NADPH oxidase inhibitors as potential therapeutic strategies. Pharmacol Res 2020; 162:105280. [PMID: 33161139 DOI: 10.1016/j.phrs.2020.105280] [Citation(s) in RCA: 51] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2020] [Revised: 10/24/2020] [Accepted: 10/27/2020] [Indexed: 02/08/2023]
Abstract
Neuropathic pain (NP) is a chronic condition that results from a lesion or disease of the nervous system, greatly impacting patients' quality of life. Current pharmacotherapy options deliver inadequate and/or insufficient responses and thus a significant unmet clinical need remains for alternative treatments in NP. Neuroinflammation, oxidative stress and their reciprocal relationship are critically involved in NP pathophysiology. In this context, new pharmacological approaches, aiming at enhancing the resolution phase of inflammation and/or restoring redox balance by targeting specific reactive oxygen species (ROS) sources, are emerging as potential therapeutic strategies for NP, with improved efficacy and safety profiles. Several reports have demonstrated that administration of exogenous specialized pro-resolving mediators (SPMs) ameliorates NP pathophysiology. Likewise, deletion or inhibition of the ROS-generating enzyme NADPH oxidase (NOX), particularly its isoforms 2 and 4, results in beneficial effects in NP models. Notably, SPMs also modulate oxidative stress and NOX also regulates neuroinflammation. By targeting neuroinflammatory and oxidative pathways, both SPMs analogues and isoform-specific NOX inhibitors are promising therapeutic strategies for NP.
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Affiliation(s)
- Luísa Teixeira-Santos
- Departamento de Biomedicina - Unidade de Farmacologia e Terapêutica, Faculdade de Medicina, Universidade do Porto, Portugal; MedInUP - Centro de Investigação Farmacológica e Inovação Medicamentosa, Universidade do Porto, Portugal.
| | - António Albino-Teixeira
- Departamento de Biomedicina - Unidade de Farmacologia e Terapêutica, Faculdade de Medicina, Universidade do Porto, Portugal; MedInUP - Centro de Investigação Farmacológica e Inovação Medicamentosa, Universidade do Porto, Portugal.
| | - Dora Pinho
- Departamento de Biomedicina - Unidade de Farmacologia e Terapêutica, Faculdade de Medicina, Universidade do Porto, Portugal; MedInUP - Centro de Investigação Farmacológica e Inovação Medicamentosa, Universidade do Porto, Portugal.
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Wang Y, Liu J, Chen R, Qi M, Tao D, Xu S. The Antagonistic Effects of Selenium Yeast (SeY) on Cadmium-Induced Inflammatory Factors and the Heat Shock Protein Expression Levels in Chicken Livers. Biol Trace Elem Res 2020; 198:260-268. [PMID: 32016827 DOI: 10.1007/s12011-020-02039-5] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2019] [Accepted: 01/07/2020] [Indexed: 12/13/2022]
Abstract
Cadmium (Cd) is a ubiquitous toxic heavy metal in the natural environment that can cause multiple organ damage to the bodies of animals and humans. Selenium yeast (SeY) is a kind of organic selenium (Se) that has a very strong function against Cd-induced injury to tissues or organs. The aim of the current study was to investigate the roles of inflammatory factors and heat shock proteins (HSPs) in inflammatory injury triggered by Cd and to analyze the protective effects of SeY on Cd-induced damnification in the livers of chickens. Two hundred 120-day-old layers were randomly divided into four groups and raised on a conventional diet, or with Se (0.5 mg/kg SeY), Cd (150 mg/kg CdCl2), or Se + Cd (0.5 mg/kg SeY and 150 mg/kg CdCl2) in their basic diets for 120 days. Then, the liver histopathology, production of nitric oxide (NO), activity of inducible NO synthase (iNOS), and mRNA and protein expression levels of inflammatory factors (iNOS, NF-κB, TNF-α, and PTGE) and heat shock proteins (HSPs 27, 40, 60, 70, and 90) were examined. The results showed that exposure to Cd obviously increased Cd accumulation, NO production, iNOS activity, inflammatory factor, and HSP mRNA and protein expression levels and further caused an inflammatory response. Supplementation with SeY had an antagonistic effect on Cd-induced inflammatory injury in chicken livers. Thus, the present study suggests that SeY can be taken as a potential therapeutic for Cd-induced liver inflammatory injury in chickens.
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Affiliation(s)
- Yong Wang
- College of Animal Science, Tarim University, Alar, 843300, Xinjiang Uygur Autonomous Region, China
| | - Junfeng Liu
- College of Animal Science, Tarim University, Alar, 843300, Xinjiang Uygur Autonomous Region, China
| | - Rong Chen
- College of Animal Science, Tarim University, Alar, 843300, Xinjiang Uygur Autonomous Region, China
| | - Meng Qi
- College of Animal Science, Tarim University, Alar, 843300, Xinjiang Uygur Autonomous Region, China
| | - Dayong Tao
- College of Animal Science, Tarim University, Alar, 843300, Xinjiang Uygur Autonomous Region, China.
| | - Shiwen Xu
- College of Animal Science, Tarim University, Alar, 843300, Xinjiang Uygur Autonomous Region, China
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Chung HY, Tam LS, Chan SCW, Cheung JPY, Wong PY, Ciang CO, Ng HY, Law MY, Lai TL, Wong CH, Hong Kong Society of Rheumatology. Risk of community-acquired pneumonia requiring hospitalization in patients with spondyloarthritis. Ther Adv Musculoskelet Dis 2020; 12:1759720X20962618. [PMID: 33133244 PMCID: PMC7576917 DOI: 10.1177/1759720x20962618] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2020] [Accepted: 09/02/2020] [Indexed: 12/17/2022] Open
Abstract
AIMS To compare the risk of community-acquired pneumonia (CAP) requiring hospitalization in spondyloarthritis (SpA) and non-specific back pain (NSBP), and to identify the risk factors for CAP in SpA. METHODS A total of 2984 patients with SpA from 11 rheumatology centers and 2526 patients with NSBP from orthopedic units were reviewed from the centralized electronic database in Hong Kong. Incidence of CAP requiring hospitalization and demographic data including age, gender, smoking and drinking status, use of sulfasalazine, individual biological-disease modifying anti-rheumatic drugs (DMARDs) used, micro-organisms, other immunosuppressants or immunosuppressive states, use of steroid for more than ½ year, and co-morbidities were identified. Risks of CAP in SpA were compared with those in NSBP using propensity score regression method. Multivariate Cox regression model was used to identify the risk factors in SpA. RESULTS CAP requiring hospitalization was found in 183 patients with SpA and 138 patients with NSBP. Increased risk for CAP was found in the following groups with SpA: all subgroups (hazard ratio (HR) 2.14, p < 0.001), without use of DMARDs (HR 2.64, p < 0.001), without psoriasis and not taking DMARDs (HR 2.38, p < 0.001). Infliximab (HR2.55, p = 0.04), smoking (HR 1.68, p = 0.003), comorbid psoriasis (HR 1.67, p = 0.003), and use of steroid for more than ½ year (HR 1.94, p = 0.003) were found to associate with CAP after adjustments for traditional risk factors. CONCLUSION Risk of CAP is increased in patients with SpA. Our data favor universal influenza and pneumococcal vaccination programs in the population. Rheumatologists should also advise smoking cessation and avoid long term steroid therapy.
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Affiliation(s)
- Ho Yin Chung
- Division of Rheumatology and Clinical Immunology, the University of Hong Kong, 102, Pokfulam Road, Hong Kong, China
| | - Lai Shan Tam
- Department of Medicine & Therapeutics, the Prince of Wales Hospital, the Chinese University of Hong Kong
| | - Shirley Chiu Wai Chan
- Division of Rheumatology and Clinical Immunology, the University of Hong Kong, Hong Kong
| | - Jason Pui Yin Cheung
- Department of Orthopaedics and Traumatology, the University of Hong Kong, Hong Kong
| | - Pui Yan Wong
- Department of Rheumatology, Tseung Kwan O Hospital, Hong Kong
| | - Chu Oi Ciang
- Department of Medicine, Queen Elizabeth Hospital, Hong Kong
| | - Hoi Yan Ng
- Division of Rheumatology, Caritas Medical Center, Hong Kong
| | - Mei Yan Law
- Department of Medicine, Alice Ho Miu Ling Nethersole Hospital, Hong Kong
| | - Tin Lok Lai
- Department of Rheumatology, Tseung Kwan O Hospital, Hong Kong
| | - Ching Han Wong
- Department of Medicine & Therapeutics, the Prince of Wales Hospital, the Chinese University of Hong Kong
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Ren B, Liu J, Wu K, Zhang J, Lv Y, Wang S, Liu L, Liu D. TNF-α-elicited miR-29b potentiates resistance to apoptosis in peripheral blood monocytes from patients with rheumatoid arthritis. Apoptosis 2020; 24:892-904. [PMID: 31473844 DOI: 10.1007/s10495-019-01567-3] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
CD14-positive monocytes from patients with rheumatoid arthritis (RA) are more resistant to apoptosis, which promotes their persistence at the inflammatory site and thereby contributes crucially to immunopathology. We sought to elucidate one mechanism underlying this unique pathogenesis: resistance to apoptosis and the potential involvement of miR-29b in this process. CD14-positive peripheral blood monocytes (PBMs) from RA patients were observed to be resistant to spontaneous apoptosis compared to PBMs from healthy volunteers. Intriguingly, expression of miR-29b was significantly upregulated in PBMs from RA patients than those from healthy volunteers, and this upregulation was correlated with RA disease activity. Functionally, forced expression of the exogenous miR-29b in CD14-positive Ctrl PBMs conferred resistance to spontaneous apoptosis and Fas-induced death, thereafter enhancing the production of major proinflammatory cytokines in there cells. Following identification of the potential miR-29b target transcripts using bioinformatic algorithms, we showed that miR-29b could directly bind to the 3'-UTR of the high-mobility group box-containing protein 1 (HBP1) and inhibited its transcription in PBMs. Importantly, stable expression of the exogenous HBP1 in differentiated THP-1 monocytes effectively abolished miR-29b-elicited resistance to Fas-induced apoptosis. Finally, among patients with RA and good clinical responses to immunotherapy, expression levels of miR-29b were significantly compromised in those treated with infliximab (a TNF-α inhibitor) but not in those treated with tocilizumab (a humanized mAb against the IL-6 receptor), pointing to a potential association between miR-29b activation and TNF-α induction. The available data collectively suggest that TNF-α-elicited miR-29b potentiates resistance to apoptosis in PBMs from RA patients via inhibition of HBP1 signaling, and testing patients for miR-29b/HBP1 expression ratios may provide more accurate prognostic information and could influence the recommended course of immunotherapy.
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Affiliation(s)
- Baodi Ren
- Department of Rheumatology and Immunology, Xi'an Institute of Rheumatology, Xi'an No.5 Hospital, No. 112 XiGuanZhengJie, Lian Hu District, Xi'an, 710082, Shaanxi Province, China.,Department of Rheumatology and Immunology, Shaanxi Hospital of Integrated Traditional Chinese and Western Medicine, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Shaanxi University of Chinese Medicine, No. 112 XiGuanZhengJie, Lian Hu District, Xi'an, 710082, Shaanxi Province, China
| | - Jiayu Liu
- Department of Rheumatology and Immunology, Xi'an Institute of Rheumatology, Xi'an No.5 Hospital, No. 112 XiGuanZhengJie, Lian Hu District, Xi'an, 710082, Shaanxi Province, China.,Core Research Laboratory, The Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, No.157 XiWu Road, Xincheng District, Xi'an, 710004, China
| | - Kunyi Wu
- Core Research Laboratory, The Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, No.157 XiWu Road, Xincheng District, Xi'an, 710004, China
| | - Junli Zhang
- Department of Rheumatology and Immunology, Xi'an Institute of Rheumatology, Xi'an No.5 Hospital, No. 112 XiGuanZhengJie, Lian Hu District, Xi'an, 710082, Shaanxi Province, China.,Department of Rheumatology and Immunology, Shaanxi Hospital of Integrated Traditional Chinese and Western Medicine, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Shaanxi University of Chinese Medicine, No. 112 XiGuanZhengJie, Lian Hu District, Xi'an, 710082, Shaanxi Province, China
| | - Yanyan Lv
- Department of Rheumatology and Immunology, Xi'an Institute of Rheumatology, Xi'an No.5 Hospital, No. 112 XiGuanZhengJie, Lian Hu District, Xi'an, 710082, Shaanxi Province, China
| | - Suzhi Wang
- Department of Rheumatology and Immunology, Xi'an Institute of Rheumatology, Xi'an No.5 Hospital, No. 112 XiGuanZhengJie, Lian Hu District, Xi'an, 710082, Shaanxi Province, China
| | - Liping Liu
- Department of Rheumatology and Immunology, Xi'an Institute of Rheumatology, Xi'an No.5 Hospital, No. 112 XiGuanZhengJie, Lian Hu District, Xi'an, 710082, Shaanxi Province, China.,Department of Rheumatology and Immunology, Shaanxi Hospital of Integrated Traditional Chinese and Western Medicine, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Shaanxi University of Chinese Medicine, No. 112 XiGuanZhengJie, Lian Hu District, Xi'an, 710082, Shaanxi Province, China
| | - Dan Liu
- Department of Rheumatology and Immunology, Xi'an Institute of Rheumatology, Xi'an No.5 Hospital, No. 112 XiGuanZhengJie, Lian Hu District, Xi'an, 710082, Shaanxi Province, China. .,Department of Rheumatology and Immunology, Shaanxi Hospital of Integrated Traditional Chinese and Western Medicine, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Shaanxi University of Chinese Medicine, No. 112 XiGuanZhengJie, Lian Hu District, Xi'an, 710082, Shaanxi Province, China. .,Core Research Laboratory, The Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, No.157 XiWu Road, Xincheng District, Xi'an, 710004, China.
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Jin L, Liu P, Yin M, Zhang M, Kuang Y, Zhu W. RIPK1: A rising star in inflammatory and neoplastic skin diseases. J Dermatol Sci 2020; 99:146-151. [PMID: 32600738 DOI: 10.1016/j.jdermsci.2020.06.001] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2020] [Revised: 06/02/2020] [Accepted: 06/02/2020] [Indexed: 11/27/2022]
Abstract
Skin diseases bring great psychological and physical impacts on patients, however, a considerable number of skin diseases still lack effective treatments, such as psoriasis, systemic lupus erythematosus, melanoma and so on. Receptor-interacting serine threonine kinase 1 (RIPK1) plays an important role in cell death, especially necroptosis, associated with inflammation and tumor. As many molecules modulate the ubiquitination of RIPK1, disruption of this checkpoint can lead to skin diseases, which can be ameliorated by RIPK1 inhibitors. This review will focus on the molecular mechanism of RIPK1 activation in inflammation as well as the current knowledges on the contribution of RIPK1 in skin diseases.
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Affiliation(s)
- Liping Jin
- Hunan Engineering Research Center of Skin Health and Disease, Xiangya Hospital, Central South University, Changsha, China
| | - Panpan Liu
- Hunan Engineering Research Center of Skin Health and Disease, Xiangya Hospital, Central South University, Changsha, China
| | - Mingzhu Yin
- Hunan Engineering Research Center of Skin Health and Disease, Xiangya Hospital, Central South University, Changsha, China
| | - Mi Zhang
- Hunan Engineering Research Center of Skin Health and Disease, Xiangya Hospital, Central South University, Changsha, China
| | - Yehong Kuang
- Hunan Engineering Research Center of Skin Health and Disease, Xiangya Hospital, Central South University, Changsha, China.
| | - Wu Zhu
- Hunan Engineering Research Center of Skin Health and Disease, Xiangya Hospital, Central South University, Changsha, China.
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Paolino G, Mercuri SR, Bearzi P, Mattozzi C. Systemic immunobiological, immunosuppressant, and oncologic agents for the treatment of dermatologic diseases during the SARS-CoV-2 (COVID-19) pandemic emergency: A quick review for a quick consultation. Dermatol Ther 2020; 33:e13537. [PMID: 32385891 PMCID: PMC7261970 DOI: 10.1111/dth.13537] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2020] [Revised: 05/01/2020] [Accepted: 05/02/2020] [Indexed: 12/19/2022]
Abstract
The precision medicine era has helped to better manage patients with immunological and oncological diseases, improving the quality of life of this class of patients. Regarding the management of these patients and positivity to severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), currently, limited data are available and information is evolving. In this quick review, we have analyzed the mechanisms of action and related infective risk of drugs used for the treatment of immune‐mediated and oncologic skin conditions during the daily clinical practice. In general, immunosuppressant and antineoplastic agents for dermatologic treatments do not require suspension and do not require special measures, if not those commonly observed. In the case of a coronavirus disease (COVID‐19) patient with complications (such as pneumonia, respiratory failure), treatment suspension should always be considered after taking into account the general condition of the patient, the risk‐benefit ratio, and the pathophysiology of COVID‐19 infection. The COVID‐19 emergency pandemic does not imply undertreatment of existing skin conditions, which together with the SARS‐CoV‐2 infection may jeopardize the patient's life.
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Affiliation(s)
- Giovanni Paolino
- Dermatology Clinic, Sapienza University of Rome, Rome, Italy.,Unit of Dermatology, IRCCS San Raffaele Hospital, Milan, Italy
| | | | - Pietro Bearzi
- Unit of Dermatology, IRCCS San Raffaele Hospital, Milan, Italy
| | - Carlo Mattozzi
- Dermatology Clinic, Sapienza University of Rome, Rome, Italy
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40
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Carballido JM, Regairaz C, Rauld C, Raad L, Picard D, Kammüller M. The Emerging Jamboree of Transformative Therapies for Autoimmune Diseases. Front Immunol 2020; 11:472. [PMID: 32296421 PMCID: PMC7137386 DOI: 10.3389/fimmu.2020.00472] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2019] [Accepted: 02/28/2020] [Indexed: 12/12/2022] Open
Abstract
Standard treatments for autoimmune and autoinflammatory disorders rely mainly on immunosuppression. These are predominantly symptomatic remedies that do not affect the root cause of the disease and are associated with multiple side effects. Immunotherapies are being developed during the last decades as more specific and safer alternatives to small molecules with broad immunosuppressive activity, but they still do not distinguish between disease-causing and protective cell targets and thus, they still have considerable risks of increasing susceptibility to infections and/or malignancy. Antigen-specific approaches inducing immune tolerance represent an emerging trend carrying the potential to be curative without inducing broad immunosuppression. These therapies are based on antigenic epitopes derived from the same proteins that are targeted by the autoreactive T and B cells, and which are administered to patients together with precise instructions to induce regulatory responses capable to restore homeostasis. They are not personalized medicines, and they do not need to be. They are precision therapies exquisitely targeting the disease-causing cells that drive pathology in defined patient populations. Immune tolerance approaches are truly transformative options for people suffering from autoimmune diseases.
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Affiliation(s)
- José M. Carballido
- Translational Medicine, Novartis Institutes for Biomedical Research, Basel, Switzerland
- Autoimmunity Transplantation and Inflammation, Novartis Institutes for Biomedical Research, Basel, Switzerland
| | - Camille Regairaz
- Autoimmunity Transplantation and Inflammation, Novartis Institutes for Biomedical Research, Basel, Switzerland
| | - Celine Rauld
- Autoimmunity Transplantation and Inflammation, Novartis Institutes for Biomedical Research, Basel, Switzerland
| | - Layla Raad
- Autoimmunity Transplantation and Inflammation, Novartis Institutes for Biomedical Research, Basel, Switzerland
| | - Damien Picard
- Translational Medicine, Novartis Institutes for Biomedical Research, Basel, Switzerland
| | - Michael Kammüller
- Translational Medicine, Novartis Institutes for Biomedical Research, Basel, Switzerland
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41
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Di Caprio R, Caiazzo G, Cacciapuoti S, Fabbrocini G, Scala E, Balato A. Safety concerns with current treatments for psoriasis in the elderly. Expert Opin Drug Saf 2020; 19:523-531. [PMID: 32056449 DOI: 10.1080/14740338.2020.1728253] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Introduction: The approach to manage psoriasis in the elderly (ages ≥65 years) patients can be challenging. They often suffer from multiple comorbidities and polypharmacy with possible adverse effects and undergo a progressive functional impairment of the immune system that increases susceptibility to infections as well as to auto-reactivity. Despite the increasing aging of the general population and although several therapies are currently available for psoriasis treatment, data regarding their use and tolerability in the elderly are quite limited.Areas covered: This review focuses on topical and systemic therapies that have been investigated in elderly patients in order to provide their safety profile in this population.Expert opinion: Conventional systemic therapies in elderly patients should be carefully dispensed and the correct dosage individually determined, taking into account the metabolism changes, organ impairment, comorbidities, concomitant medications, and contraindications. Apremilast, due to its satisfactory safety profile and low risk of drug interactions, results as an appropriate treatment option for elderly patients. Biologics (TNF-α, IL-12/23, IL-17, and IL-23 inhibitors) come out as safe and long-term options for the management of these patients resulting not associated with a higher risk of adverse events.
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Affiliation(s)
- Roberta Di Caprio
- Department of Clinical Medicine and Surgery - Section of Dermatology, University of Naples Federico II, Italy
| | - Giuseppina Caiazzo
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy
| | - Sara Cacciapuoti
- Department of Clinical Medicine and Surgery - Section of Dermatology, University of Naples Federico II, Italy
| | - Gabriella Fabbrocini
- Department of Clinical Medicine and Surgery - Section of Dermatology, University of Naples Federico II, Italy
| | - Emanuele Scala
- Department of Clinical Medicine and Surgery - Section of Dermatology, University of Naples Federico II, Italy
| | - Anna Balato
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy
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Kumano K, Takita M, Vasu S, Darden C, Lawrence M, Beecherl E, Gupta A, Onaca N, Naziruddin B. Impact of microbial contamination of the islet product during total pancreatectomy with islet autotransplantation. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2020; 27:211-218. [PMID: 31944603 DOI: 10.1002/jhbp.709] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/02/2019] [Revised: 11/22/2019] [Accepted: 01/08/2020] [Indexed: 12/17/2022]
Abstract
BACKGROUND The combined use of interleukin-1β and tumor necrosis factor-α blockers in the peritransplant period has improved outcomes of total pancreatectomy with islet autotransplantation (TPIAT). However, these drugs may suppress the immune system, resulting in severe infection. METHODS We retrospectively investigated the impact of microbial-contaminated islet product on posttransplant complications and metabolic outcomes of TPIAT patients receiving the IL-1β and TNF-blockade treatment at our center. RESULTS Among 108 TPIAT patients, 37 patients (34%) received contaminated products. Preoperative stent treatment and fibrosis score were independent risk factors for the contamination. There were no significant differences between the contaminated and noncontaminated product groups in posttransplant infectious complication rate, length of hospitalization, or readmission rate. However, islet equivalents (P < .0001) and insulin independence rate (P = .036) at 6 months were significantly lower for patients receiving contaminated product. CONCLUSIONS These results suggest that combined anti-inflammatory drug use is safe and well tolerated in TPIAT patients who receive contaminated islet product and does not increase the rate of infectious complications; however, contaminated islet product is associated with poor metabolic outcomes.
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Affiliation(s)
- Kenjiro Kumano
- Baylor Scott and White Research Institute, Dallas, TX, USA
| | | | - Srividya Vasu
- Baylor Scott and White Research Institute, Dallas, TX, USA
| | | | | | | | - Amar Gupta
- Baylor Simmons Transplant Institute, Dallas, TX, USA
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Adami G, Saag KG, Chapurlat RD, Guañabens N, Haugeberg G, Lems WF, Matijevic R, Peel N, Poddubnyy D, Geusens P. Balancing benefits and risks in the era of biologics. Ther Adv Musculoskelet Dis 2019; 11:1759720X19883973. [PMID: 31695755 PMCID: PMC6820177 DOI: 10.1177/1759720x19883973] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2019] [Accepted: 10/01/2019] [Indexed: 12/28/2022] Open
Abstract
Biologics are substances synthetized from biological sources used in the prevention and treatment of several diseases. Rheumatologists have many years of experience with biologics for the treatment of immune-mediated diseases and osteoporosis. Randomized clinical trials and postmarketing studies have demonstrated that treatment with biologics can result, albeit infrequently, in serious adverse events. To date, several risk mitigation strategies have been identified and implemented. The objective of the present perspective review is to examine the risk mitigation strategies of biologic treatments, with special focus on anti-tumor necrosis factors and denosumab.
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Affiliation(s)
- Giovanni Adami
- Rheumatology Unit, University of Verona, Pz Scuro 10, 37135, Verona, Italy
| | - Kenneth G Saag
- Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL, USA
| | | | - Nuria Guañabens
- Rheumatology Department, Hospital Clinic, CIBERehd, IDIBAPS, University of Barcelona, Barcelona, Spain
| | - Glenn Haugeberg
- Division of Rheumatology, Medicine Department, Southern Hospital Trust, Trondheim, Norway
| | - Willem F Lems
- Amsterdam UMC, location VUmc, Amsterdam, the Netherlands
| | | | - Nicola Peel
- Metabolic Bone Centre, Northern General Hospital Sheffield, UK
| | - Denis Poddubnyy
- Department of Gastroenterology, Infectious Diseases, and Rheumatology, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Piet Geusens
- CAPHRI School for Public Health and Primary Care, Maastricht University, Maastricht, the Netherlands
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Fernández-Ruiz M. Assessment of latent infections in patients receiving biological therapies. REVISTA ESPANOLA DE QUIMIOTERAPIA : PUBLICACION OFICIAL DE LA SOCIEDAD ESPANOLA DE QUIMIOTERAPIA 2019; 32 Suppl 2:63-68. [PMID: 31475814 PMCID: PMC6755370] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
The use of biological (or targeted) therapies constitutes a major advance in the management of autoinflammatory and malignant diseases. However, due to the selective effect of these agents on the host's immune response, reactivation of certain pathogens that cause latent infection is to be expected. The most relevant concern is the risk of reactivation of latent tuberculosis infection (LTBI) and progression to active tuberculosis among patients treated with agents targeting tumor necrosis factor (TNF)-α. Systematic screening for LTBI at base-line with appropriate initiation of antituberculous treatment, if needed, is mandatory in this patient population as risk minimization strategy. In addition, reactivation of hepatitis B virus induced by B-cell-depleting (anti-CD20) and anti-TNF-α agents should be also prevented among HBsAg-positive patients and those with isolated anti-HBc IgG positivity (risk of "occult HBV infection"). The present review summarizes available evidence regarding the risk of reactivation of these latent infections induced by newer biological agents, as well as the recommendations included in the most recent guidelines.
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Affiliation(s)
- Mario Fernández-Ruiz
- Unit of Infectious Diseases, Hospital Universitario “12 de Octubre”, Instituto de Investigación Hospital “12 de Octubre” (imas12), Madrid, Spain,Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0002), Instituto de Salud Carlos III, Madrid, Spain,Correspondence: Mario Fernández-Ruiz Unit of Infectious Diseases. Hospital Universitario “12 de Octubre”. Centro de Actividades Ambulatorias, 2ª planta, bloque D. Avda. de Córdoba, s/n. Postal code 28041. Madrid, Spain. Phone: +34 913908000 - Fax: +34 914695775. E-mail:
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