|
1
|
Kosanam S, Pasupula R. Effect of Methyl Glycoside on Apoptosis and Oxidative Stress in Hypoxia Induced-Reoxygenated H9C2 Cell Lines. Cell Biochem Biophys 2025; 83:1045-1056. [PMID: 39292425 DOI: 10.1007/s12013-024-01539-8] [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] [Accepted: 09/09/2024] [Indexed: 09/19/2024]
Abstract
This study focuses on key genes (Caspase-3, JAK2, BCL2L1 and MAPK8) and their modulation in response to hypoxia-induced stress using Methyl Glycoside (MG), a small molecule spectroscopically screened from Aganosma dichotoma. Hypoxia/reoxygenation (H/R) induced H9C2 cells, pre- treated with MG, were subjected to cell viability assay, free radical scavenging activities (catalase, GST, GSH-Px, SOD), caspase activity, mitochondrial membrane potential, and gene expression profiling through standard assays and molecular techniques. Results indicated that MG treatment, has potential protective effects against H/R induced stress in H9C2 cell lines. Cell viability assays showed that MG maintained cellular viability with significant protection (P < 0.05) observed from 10 µM. Free radical scavenging assays revealed that MG, enhanced detoxification mechanisms and exhibited potential antioxidant effect in a significantly (P < 0.05) in a dose dependant manner. MG pre-treatment in H9C2 cells protected cellular damage from caspase activity, cells exhibited high mitochondrial membrane potential, and gene expression profiles, including upregulation of anti-apoptotic BCL2L1 and modulation of stress-responsive genes like CASP3, JAK2 and MAPK8. Hence, MG exhibited concentration-dependent protective effects on viability, oxidative stress, and apoptosis-related pathways, laying the foundation for further exploration and translational applications in cardiovascular interventions.
Collapse
Affiliation(s)
- Sreya Kosanam
- Department. of Pharmacology, College of Pharmacy, Koneru Lakshmaiah Education Foundation, KL deemed to be University, Green Fields, Vaddeswaram, Andhra Pradesh, India
| | - Rajeshwari Pasupula
- Department. of Pharmacology, College of Pharmacy, Koneru Lakshmaiah Education Foundation, KL deemed to be University, Green Fields, Vaddeswaram, Andhra Pradesh, India.
| |
Collapse
|
|
2
|
Mirza Y, Sari F, Yılmaz PD, Küçük A. Evaluation of abdominal and lumbar multifidus muscles thickness and relation to endurance, pain, fatigue and functional mobility in patients with Fibromyalgia syndrome: a case-control study. Rheumatol Int 2025; 45:56. [PMID: 39982517 PMCID: PMC11845533 DOI: 10.1007/s00296-025-05813-7] [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: 12/25/2024] [Accepted: 02/10/2025] [Indexed: 02/22/2025]
Abstract
OBJECTIVE The aim of present study was to compare abdominal (transversus abdominis (TrA), internal oblique (IO) and external oblique (EO)) and lumbar multifidus muscles (LM) evaluated with ultrasonographic (US) imaging in patients with FM (Fibromyalgia) and asymptomatic individuals and to examine the relationship between these muscle thickness and endurance, pain, fatigue and functional mobility. METHODS Women with FM group (n: 53, age: 45.96 ± 9.96 years), and asymptomatic control group (n: 49, age: 45.12 ± 7.28), were included in this study. Pain severity, disease activity, physical activity level, fatique, thickness of TrA, IO, EO and LM muscles and endurance, and functional mobility were evaluated with the Visual Analogue Scale (VAS), Fibromyalgia Impact Questionnaire (FIQ), International Physical Activity Questionnaire- Short Form (IPAQ-SF), Fatigue Severity Scale (FSS), US imaging, McGill core endurance tests, and physical fitness tests, respectively. FM patients were classified according to the FSS score. RESULTS The thickness of the IO (right side) (p = 0.013) and LM (both sides) (p < 0.001) muscles, lumbopelvic muscle endurance (all p < 0.001) and physical fitness tests (all p < 0.001) were lower in FM group compared to the asymptomatic group. No statistically significant differences were found in TrA, IO (left side), EO muscles thickness between the two groups (all p > 0.05). LM muscle thickness was significantly correlated with lumbopelvic muscle endurance (all p < 0.05), physical fitness tests (all p < 0.001) and fatique (p = 0.001). Moreover, significant differences in LM muscle thickness (p = 0.007), trunk flexor muscle endurance (p = 0.016), left trunk lateral flexor muscle endurance (p = 0.045) and 30-s chair stand test (p = 0.025) in favor of the low-fatigue group were detected. CONCLUSION The thickness of LM muscle, lumbopelvik endurance and functional mobility in FM patients have been affected negatively. These findings should be considered in management of FM.
Collapse
Affiliation(s)
- Yasemin Mirza
- Faculty of Health Sciences, Department of Physiotherapy and Rehabilitation, Necmettin Erbakan University, Konya, Turkey.
| | - Fulden Sari
- Faculty of Physical Therapy and Rehabilitation, Department of Physiotherapy and Rehabilitation, Bingol University, Bingol, Turkey
| | - Pınar Diydem Yılmaz
- Faculty of Medicine, Department of Radiology, Necmettin Erbakan University, Konya, Turkey
| | - Adem Küçük
- Faculty of Medicine, Department of Internal Medicine, Division of Rheumatology, Necmettin Erbakan University, Konya, Turkey
| |
Collapse
|
|
3
|
Kodali M, Madhu LN, Somayaji Y, Attaluri S, Huard C, Panda PK, Shankar G, Rao S, Shuai B, Gonzalez JJ, Oake C, Hering C, Babu RS, Kotian S, Shetty AK. Residual microglia following short-term PLX5622 treatment in 5xFAD mice exhibit diminished NLRP3 inflammasome and mTOR signaling, and enhanced autophagy. Aging Cell 2025; 24:e14398. [PMID: 39571180 PMCID: PMC11822669 DOI: 10.1111/acel.14398] [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: 06/19/2024] [Revised: 10/09/2024] [Accepted: 10/17/2024] [Indexed: 11/27/2024] Open
Abstract
While moderately activated microglia in Alzheimer's disease (AD) are pivotal in clearing amyloid beta (Aβ), hyperactivated microglia perpetuate neuroinflammation. Prior investigations reported that the elimination of ~80% of microglia through inhibition of the colony-stimulating factor 1 receptor (CSF1R) during the advanced stage of neuroinflammation in 5xFamilial AD (5xFAD) mice mitigates synapse loss and neurodegeneration. Furthermore, prolonged CSF1R inhibition diminished the development of parenchymal plaques. Nonetheless, the effects of short-term CSF1R inhibition during the early stages of neuroinflammation on residual microglia are unknown. Therefore, we investigated the effects of 10-day CSF1R inhibition using PLX5622 in three-month-old female 5xFAD mice, a stage characterized by the onset of neuroinflammation and minimal Aβ plaques. We observed ~65% microglia depletion in the hippocampus and cerebral cortex. The leftover microglia displayed a noninflammatory phenotype with reduced NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome complexes. Moreover, plaque-associated microglia were reduced with diminished Clec7a expression. Additionally, phosphorylated S6 ribosomal protein and the protein sequestosome 1 analysis suggested reduced mechanistic targets of rapamycin (mTOR) signaling and autophagy in microglia and neurons within the hippocampus and cerebral cortex. Biochemical assays validated the inhibition of NLRP3 inflammasome activation, decreased mTOR signaling in the hippocampus and cerebral cortex, and enhanced autophagy in the hippocampus. However, short-term CSF1R inhibition did not influence Aβ plaques, soluble Aβ-42 levels, astrocyte hypertrophy, or hippocampal neurogenesis. Thus, short-term CSF1R inhibition during the early stages of neuroinflammation in 5xFAD mice promotes the retention of homeostatic microglia with diminished inflammasome activation and mTOR signaling, alongside increased autophagy.
Collapse
Affiliation(s)
- Maheedhar Kodali
- Institute for Regenerative Medicine, Department of Cell Biology and GeneticsTexas A&M University Health Science Center School of MedicineCollege StationTexasUSA
| | - Leelavathi N. Madhu
- Institute for Regenerative Medicine, Department of Cell Biology and GeneticsTexas A&M University Health Science Center School of MedicineCollege StationTexasUSA
| | - Yogish Somayaji
- Institute for Regenerative Medicine, Department of Cell Biology and GeneticsTexas A&M University Health Science Center School of MedicineCollege StationTexasUSA
| | - Sahithi Attaluri
- Institute for Regenerative Medicine, Department of Cell Biology and GeneticsTexas A&M University Health Science Center School of MedicineCollege StationTexasUSA
| | - Charles Huard
- Institute for Regenerative Medicine, Department of Cell Biology and GeneticsTexas A&M University Health Science Center School of MedicineCollege StationTexasUSA
| | - Prashanta Kumar Panda
- Institute for Regenerative Medicine, Department of Cell Biology and GeneticsTexas A&M University Health Science Center School of MedicineCollege StationTexasUSA
| | - Goutham Shankar
- Institute for Regenerative Medicine, Department of Cell Biology and GeneticsTexas A&M University Health Science Center School of MedicineCollege StationTexasUSA
| | - Shama Rao
- Institute for Regenerative Medicine, Department of Cell Biology and GeneticsTexas A&M University Health Science Center School of MedicineCollege StationTexasUSA
| | - Bing Shuai
- Institute for Regenerative Medicine, Department of Cell Biology and GeneticsTexas A&M University Health Science Center School of MedicineCollege StationTexasUSA
| | - Jenny J. Gonzalez
- Institute for Regenerative Medicine, Department of Cell Biology and GeneticsTexas A&M University Health Science Center School of MedicineCollege StationTexasUSA
| | - Chris Oake
- Institute for Regenerative Medicine, Department of Cell Biology and GeneticsTexas A&M University Health Science Center School of MedicineCollege StationTexasUSA
| | - Catherine Hering
- Institute for Regenerative Medicine, Department of Cell Biology and GeneticsTexas A&M University Health Science Center School of MedicineCollege StationTexasUSA
| | - Roshni Sara Babu
- Institute for Regenerative Medicine, Department of Cell Biology and GeneticsTexas A&M University Health Science Center School of MedicineCollege StationTexasUSA
| | - Sanya Kotian
- Institute for Regenerative Medicine, Department of Cell Biology and GeneticsTexas A&M University Health Science Center School of MedicineCollege StationTexasUSA
| | - Ashok K. Shetty
- Institute for Regenerative Medicine, Department of Cell Biology and GeneticsTexas A&M University Health Science Center School of MedicineCollege StationTexasUSA
| |
Collapse
|
|
4
|
Kim MJ, Hwang HS, Choi JH, Yoo ES, Jang MI, Lee J, Oh SM. Development of a multi-analysis model using an epithelial-fibroblast co-culture system as an alternative to animal testing. Environ Anal Health Toxicol 2024; 39:e2024024-0. [PMID: 39536704 PMCID: PMC11560297 DOI: 10.5620/eaht.2024024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2024] [Accepted: 09/13/2024] [Indexed: 11/16/2024] Open
Abstract
The evaluation of respiratory chemical substances has been mostly performed in animal tests (OECD TG 403, TG 412, TG 413, etc.). However, there have been ongoing discussions about the limited use of these inhalation toxicity tests due to differences in the anatomical structure of the respiratory tract, difficulty in exposure, laborious processes, and ethical reasons. Alternative animal testing methods that mimic in vivo testing are required. Therefore, in this study, we established a co-culture system composed of differentiated epithelial cells under an air-liquid interface (ALI) system in the apical part and fibroblasts in the basal part. This system was designed to mimic the wound-healing mechanism in the respiratory system. In addition, we developed a multi-analysis system that simultaneously performs toxicological and functional evaluations. Several individual assays were used sequentially in a multi-analysis model for pulmonary toxicity. Briefly, cytokine analysis, histology, and cilia motility were measured in the apical part, and cell migration and gel contraction assay were performed by exposing MRC-5 cells to the basal culture. First, human airway epithelial cells from bronchial (hAECB) were cultured under air-liquid interface (ALI) system conditions and validated pseudostratified epithelium by detecting differentiation-related epithelial markers using Transepithelial Electrical Resistance (TEER) measurement, Hematoxylin and Eosin (H&E) staining, and immunocytochemistry (ICC) staining. Afterward, the co-culture cells exposed to Transforming growth factor-beta 1 (TGF-β1), a key mediator of pulmonary fibrosis, induced significant toxicological responses such as cytotoxicity, cell migration, and gel contraction, which are wound-healing markers. In addition, cilia motility in epithelial cells was significantly decreased compared to control. Therefore, the multi-analysis model with a 3D epithelial-fibroblast co-culture system is expected to be useful in predicting pulmonary toxicity as a simple and efficient high-throughput screening method and as an alternative to animal testing.
Collapse
Affiliation(s)
- Min-Ju Kim
- Department of Bio-application toxicity, Hoseo University, Asan, Republic of Korea
| | - Hee-Sung Hwang
- Department of Bio-application toxicity, Hoseo University, Asan, Republic of Korea
| | - Jee Hoon Choi
- Department of Bio-application toxicity, Hoseo University, Asan, Republic of Korea
| | - Eun-Seon Yoo
- Department of Bio-application toxicity, Hoseo University, Asan, Republic of Korea
| | - Mi-Im Jang
- Department of Bio-application toxicity, Hoseo University, Asan, Republic of Korea
| | - Juhee Lee
- Department of ICT Automotive Engineering, Hoseo University, Asan, Republic of Korea
| | - Seung Min Oh
- Department of Bio-application toxicity, Hoseo University, Asan, Republic of Korea
- Department of Animal Health and Welfare, Hoseo University, Asan, Republic of Korea
| |
Collapse
|
|
5
|
Giacomarra M, La Torre M, Montana G. Effects of Inhibition of IKK Kinase Phosphorylation On the Cellular Defence System and HSP90 Activity. Inflammation 2024; 47:74-83. [PMID: 37640833 PMCID: PMC10799094 DOI: 10.1007/s10753-023-01894-3] [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: 05/01/2023] [Revised: 07/31/2023] [Accepted: 08/18/2023] [Indexed: 08/31/2023]
Abstract
The present study was conceived to examine the effects of inhibition of BMS-345541 mediated IKK kinase phosphorylation on the cellular defence system as well as on anti-inflammatory response and HSP90 activity. The analysis was conducted in A549 cell line, since such cells carry a homozygous Keap1 mutation (G333C) that alters its interaction with Nrf2. Recent data have highlighted that Keap1, HSP90 protein and IKK kinase interact reciprocally and particularly Keap1 protein is involved in HSP90 and anti-oxidative pathway regulation. The activities of COX2 and HO1 were investigated by real time and immunoblot analysis along with the synthesis and activity of inducible forms of heat shock protein HSP90. Pre-treatment with IKK kinase inhibitor proved to be a protective means to lower the activity of inflammatory cascade, so preventing the formation of excessive amounts of pro-inflammatory molecules. The inhibitor of IKK kinase BMS-345541 was added to cultured A549 cells before the Escherichia coli lipopolysaccharide (LPS) addition. The viability of the cells was determined after 1-24 h incubation with BMS-345541 at concentrations ranging from 1,25-5 µM. It was found that 1 µM concentration does not significantly affected cell viability (data not shown). As a result, the treatment with 1 μM of BMS-345541 induces the inhibition of IKK phosphorylation. In the A549 cells treated with BMS-345541 and LPS, COX2 activity is not induced: mRNA and protein levels have not increased, while there is an increase in the level of HSP90, HO1 proteins and mRNA. The results suggest that the IKK inhibition is effective in the reduction of the inflammatory response thanks to mechanisms involving both the heat shock cellular defense system and the antioxidative pathway.
Collapse
Affiliation(s)
- Miriam Giacomarra
- Istituto di Ricerca e Innovazione Biomedica, Consiglio Nazionale delle Ricerche (CNR), Via Ugo La Malfa 153, 90146, Palermo, Italy
| | - Martina La Torre
- Consiglio Nazionale delle Ricerche (CNR), Istituto di Farmacologia Traslazionale, 00133, Rome, Italy
| | - Giovanna Montana
- Consiglio Nazionale delle Ricerche (CNR), Istituto di Farmacologia Traslazionale, 00133, Rome, Italy.
| |
Collapse
|
|
6
|
Wang Y, Shi C, Guo J, Zhang Y, Gong Z. Distinct Types of Cell Death and Implications in Liver Diseases: An Overview of Mechanisms and Application. J Clin Transl Hepatol 2023; 11:1413-1424. [PMID: 37719956 PMCID: PMC10500292 DOI: 10.14218/jcth.2023.00132] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2023] [Revised: 05/17/2023] [Accepted: 07/12/2023] [Indexed: 09/19/2023] Open
Abstract
Cell death is associated with a variety of liver diseases, and hepatocyte death is a core factor in the occurrence and progression of liver diseases. In recent years, new cell death modes have been identified, and certain biomarkers have been detected in the circulation during various cell death modes that mediate liver injury. In this review, cell death modes associated with liver diseases are summarized, including some cell death modes that have emerged in recent years. We described the mechanisms associated with liver diseases and summarized recent applications of targeting cell death in liver diseases. It provides new ideas for the diagnosis and treatment of liver diseases. In addition, multiple cell death modes can contribute to the same liver disease. Different cell death modes are not isolated, and they interact with each other in liver diseases. Future studies may focus on exploring the regulation between various cell death response pathways in liver diseases.
Collapse
Affiliation(s)
- Yukun Wang
- Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
| | - Chunxia Shi
- Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
| | - Jin Guo
- Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
| | - Yanqiong Zhang
- Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
| | - Zuojiong Gong
- Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
| |
Collapse
|
|
7
|
Chaudhary MR, Chaudhary S, Sharma Y, Singh TA, Mishra AK, Sharma S, Mehdi MM. Aging, oxidative stress and degenerative diseases: mechanisms, complications and emerging therapeutic strategies. Biogerontology 2023; 24:609-662. [PMID: 37516673 DOI: 10.1007/s10522-023-10050-1] [Citation(s) in RCA: 23] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2023] [Accepted: 06/28/2023] [Indexed: 07/31/2023]
Abstract
Aging accompanied by several age-related complications, is a multifaceted inevitable biological progression involving various genetic, environmental, and lifestyle factors. The major factor in this process is oxidative stress, caused by an abundance of reactive oxygen species (ROS) generated in the mitochondria and endoplasmic reticulum (ER). ROS and RNS pose a threat by disrupting signaling mechanisms and causing oxidative damage to cellular components. This oxidative stress affects both the ER and mitochondria, causing proteopathies (abnormal protein aggregation), initiation of unfolded protein response, mitochondrial dysfunction, abnormal cellular senescence, ultimately leading to inflammaging (chronic inflammation associated with aging) and, in rare cases, metastasis. RONS during oxidative stress dysregulate multiple metabolic pathways like NF-κB, MAPK, Nrf-2/Keap-1/ARE and PI3K/Akt which may lead to inappropriate cell death through apoptosis and necrosis. Inflammaging contributes to the development of inflammatory and degenerative diseases such as neurodegenerative diseases, diabetes, cardiovascular disease, chronic kidney disease, and retinopathy. The body's antioxidant systems, sirtuins, autophagy, apoptosis, and biogenesis play a role in maintaining homeostasis, but they have limitations and cannot achieve an ideal state of balance. Certain interventions, such as calorie restriction, intermittent fasting, dietary habits, and regular exercise, have shown beneficial effects in counteracting the aging process. In addition, interventions like senotherapy (targeting senescent cells) and sirtuin-activating compounds (STACs) enhance autophagy and apoptosis for efficient removal of damaged oxidative products and organelles. Further, STACs enhance biogenesis for the regeneration of required organelles to maintain homeostasis. This review article explores the various aspects of oxidative damage, the associated complications, and potential strategies to mitigate these effects.
Collapse
Affiliation(s)
- Mani Raj Chaudhary
- Department of Biochemistry, School of Bioengineering and Biosciences, Lovely Professional University, Phagwara, Punjab, 144411, India
| | - Sakshi Chaudhary
- Department of Biochemistry, School of Bioengineering and Biosciences, Lovely Professional University, Phagwara, Punjab, 144411, India
| | - Yogita Sharma
- Department of Biochemistry, School of Bioengineering and Biosciences, Lovely Professional University, Phagwara, Punjab, 144411, India
| | - Thokchom Arjun Singh
- Department of Biochemistry, School of Bioengineering and Biosciences, Lovely Professional University, Phagwara, Punjab, 144411, India
| | - Alok Kumar Mishra
- Department of Microbiology, School of Bioengineering and Biosciences, Lovely Professional University, Phagwara, Punjab, 144411, India
| | - Shweta Sharma
- Chitkara School of Health Sciences, Chitkara University, Chandigarh, Punjab, 140401, India
| | - Mohammad Murtaza Mehdi
- Department of Biochemistry, School of Bioengineering and Biosciences, Lovely Professional University, Phagwara, Punjab, 144411, India.
| |
Collapse
|
|
8
|
Jiang P, Li Q, Luo Y, Luo F, Che Q, Lu Z, Yang S, Yang Y, Chen X, Cai Y. Current status and progress in research on dressing management for diabetic foot ulcer. Front Endocrinol (Lausanne) 2023; 14:1221705. [PMID: 37664860 PMCID: PMC10470649 DOI: 10.3389/fendo.2023.1221705] [Citation(s) in RCA: 36] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2023] [Accepted: 07/31/2023] [Indexed: 09/05/2023] Open
Abstract
Diabetic foot ulcer (DFU) is a major complication of diabetes and is associated with a high risk of lower limb amputation and mortality. During their lifetime, 19%-34% of patients with diabetes can develop DFU. It is estimated that 61% of DFU become infected and 15% of those with DFU require amputation. Furthermore, developing a DFU increases the risk of mortality by 50%-68% at 5 years, higher than some cancers. Current standard management of DFU includes surgical debridement, the use of topical dressings and wound decompression, vascular assessment, and glycemic control. Among these methods, local treatment with dressings builds a protective physical barrier, maintains a moist environment, and drains the exudate from DFU wounds. This review summarizes the development, pathophysiology, and healing mechanisms of DFU. The latest research progress and the main application of dressings in laboratory and clinical stage are also summarized. The dressings discussed in this review include traditional dressings (gauze, oil yarn, traditional Chinese medicine, and others), basic dressings (hydrogel, hydrocolloid, sponge, foam, film agents, and others), bacteriostatic dressings, composite dressings (collagen, nanomaterials, chitosan dressings, and others), bioactive dressings (scaffold dressings with stem cells, decellularized wound matrix, autologous platelet enrichment plasma, and others), and dressings that use modern technology (3D bioprinting, photothermal effects, bioelectric dressings, microneedle dressings, smart bandages, orthopedic prosthetics and regenerative medicine). The dressing management challenges and limitations are also summarized. The purpose of this review is to help readers understand the pathogenesis and healing mechanism of DFU, help physicians select dressings correctly, provide an updated overview of the potential of biomaterials and devices and their application in DFU management, and provide ideas for further exploration and development of dressings. Proper use of dressings can promote DFU healing, reduce the cost of treating DFU, and reduce patient pain.
Collapse
Affiliation(s)
- Pingnan Jiang
- Department of Endocrinology and Metabolism, the Second Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Qianhang Li
- Department of Endocrinology and Metabolism, the Second Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Yanhong Luo
- Department of Endocrinology and Metabolism, the Second Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Feng Luo
- Department of Endocrinology and Metabolism, the Second Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Qingya Che
- Department of Endocrinology and Metabolism, the Second Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Zhaoyu Lu
- Department of Endocrinology and Metabolism, the Second Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Shuxiang Yang
- Department of Endocrinology and Metabolism, the Second Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Yan Yang
- Department of Endocrinology and Metabolism, the Second Affiliated Hospital of Zunyi Medical University, Zunyi, China
- Department of Endocrinology and Metabolism, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China
| | - Xia Chen
- Department of Endocrinology, Kweichow Moutai Hospital, Renhuai, Guizhou, China
| | - Yulan Cai
- Department of Endocrinology and Metabolism, the Second Affiliated Hospital of Zunyi Medical University, Zunyi, China
- Department of Endocrinology and Metabolism, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China
- Department of Endocrinology, Kweichow Moutai Hospital, Renhuai, Guizhou, China
| |
Collapse
|
|
9
|
Xi G, Cheng R, Liang L, Che N, Wang Y, Zhao N, Liang X, Shao B, Zhao X, Zhang D. High expression of RNF31 is associated with tumor immune cell infiltration and leads to poor prognosis in liver hepatocellular carcinoma. Sci Rep 2023; 13:6957. [PMID: 37117215 PMCID: PMC10147728 DOI: 10.1038/s41598-023-32692-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2022] [Accepted: 03/31/2023] [Indexed: 04/30/2023] Open
Abstract
Ring finger protein 31 (RNF31) has been found to play an important role in tumor immunity. However, the role of RNF31 in liver hepatocellular carcinoma (LIHC) has not been reported. Therefore, we investigated the expression and prognostic value of RNF31 in patients with LIHC and explored its relationship with immune cell infiltration. The Cancer Genome Atlas liver hepatocellular carcinoma (TCGA-LIHC) dataset was downloaded to analyse the impact of RNF31 on the prognosis and immune cell infiltration of LIHC. The Tumor Immune Estimation Resource (TIMER) database was used to analyse the correlation between RNF31 and tumor immune cell infiltration in LIHC. Additionally, we analysed the relationship between RNF31 and tumor necrosis factor (TNF) as well as the interferon-gamma (IFN-γ) signaling pathway. The expression of RNF31 in LIHC was significantly higher than that in normal tissues. Increased RNF31 expression was associated with decreased overall survival (OS) and relapse-free survival (RFS). An increase in RNF31 expression was closely related to the infiltration levels of immune cells (e.g., natural killer (NK) cells, CD8 + T cells, and B cells). RNF31 was also positively correlated with the expression of immune checkpoint genes in LIHC. Moreover, RNF31 may participate in TNF and IFN-γ signaling pathways. In conclusion, RNF31 is a potentially valuable prognostic biomarker in LIHC. RNF31 is also associated with immune cell infiltration in LIHC. RNF31 may be a potential target for immunotherapy of LIHC.
Collapse
Affiliation(s)
- Guifu Xi
- Department of Pathology, Tianjin Medical University, Tianjin, 300070, China
| | - Runfen Cheng
- National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China
| | - Leiting Liang
- Department of Pathology, Tianjin Medical University, Tianjin, 300070, China
| | - Na Che
- Department of Pathology, Tianjin Medical University, Tianjin, 300070, China
| | - Yalei Wang
- National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China
| | - Nan Zhao
- Department of Pathology, Tianjin Medical University, Tianjin, 300070, China
| | - Xiaohui Liang
- Department of Pathology, Tianjin Medical University, Tianjin, 300070, China
| | - Bing Shao
- National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China
| | - Xiulan Zhao
- Department of Pathology, Tianjin Medical University, Tianjin, 300070, China.
| | - Danfang Zhang
- Department of Pathology, Tianjin Medical University, Tianjin, 300070, China.
| |
Collapse
|
|
10
|
Xu C, Guo H, Li R, Lan X, Zhang Y, Xie Q, Zhu D, Mu Q, Wang Z, An M, Xia Z, Wu Y. Transcriptomic and functional analyses reveal the molecular mechanisms underlying Fe-mediated tobacco resistance to potato virus Y infection. FRONTIERS IN PLANT SCIENCE 2023; 14:1163679. [PMID: 37063211 PMCID: PMC10098458 DOI: 10.3389/fpls.2023.1163679] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 02/11/2023] [Accepted: 03/15/2023] [Indexed: 06/19/2023]
Abstract
Potato virus Y (PVY) mainly infects Solanaceous crops, resulting in considerable losses in the yield and quality. Iron (Fe) is involved in various biological processes in plants, but its roles in resistance to PVY infection has not been reported. In this study, foliar application of Fe could effectively inhibit early infection of PVY, and a full-length transcriptome and Illumina RNA sequencing was performed to investigate its modes of action in PVY-infected Nicotiana tabacum. The results showed that 18,074 alternative splicing variants, 3,654 fusion transcripts, 3,086 long non-coding RNAs and 14,403 differentially expressed genes (DEGs) were identified. Specifically, Fe application down-regulated the expression levels of the DEGs related to phospholipid hydrolysis, phospholipid signal, cell wall biosynthesis, transcription factors (TFs) and photosystem I composition, while those involved with photosynthetic electron transport chain (PETC) were up-regulated at 1 day post inoculation (dpi). At 3 dpi, these DEGs related to photosystem II composition, PETC, molecular chaperones, protein degradation and some TFs were up-regulated, while those associated with light-harvesting, phospholipid hydrolysis, cell wall biosynthesis were down-regulated. At 9 dpi, Fe application had little effects on resistance to PVY infection and transcript profiles. Functional analysis of these potentially critical DEGs was thereafter performed using virus-induced gene silencing approaches and the results showed that NbCat-6A positively regulates PVY infection, while the reduced expressions of NbWRKY26, NbnsLTP, NbFAD3 and NbHSP90 significantly promote PVY infection in N. benthamiana. Our results elucidated the regulatory network of Fe-mediated resistance to PVY infection in plants, and the functional candidate genes also provide important theoretical bases to further improve host resistance against PVY infection.
Collapse
Affiliation(s)
- Chuantao Xu
- Liaoning Key Laboratory of Plant Pathology, College of Plant Protection, Shenyang Agricultural University, Shenyang, China
- Luzhou City Company of Sichuan Province Tobacco Company, Luzhou, China
| | - Huiyan Guo
- Liaoning Key Laboratory of Plant Pathology, College of Plant Protection, Shenyang Agricultural University, Shenyang, China
| | - Rui Li
- Liaoning Key Laboratory of Plant Pathology, College of Plant Protection, Shenyang Agricultural University, Shenyang, China
| | - Xinyu Lan
- Liaoning Key Laboratory of Plant Pathology, College of Plant Protection, Shenyang Agricultural University, Shenyang, China
| | - Yonghui Zhang
- Luzhou City Company of Sichuan Province Tobacco Company, Luzhou, China
| | - Qiang Xie
- Luzhou City Company of Sichuan Province Tobacco Company, Luzhou, China
| | - Di Zhu
- Guizhou Qianxinan Prefectural Tobacco Company, Xingyi, China
| | - Qing Mu
- Guizhou Qianxinan Prefectural Tobacco Company, Xingyi, China
| | - Zhiping Wang
- Liaoning Key Laboratory of Plant Pathology, College of Plant Protection, Shenyang Agricultural University, Shenyang, China
| | - Mengnan An
- Liaoning Key Laboratory of Plant Pathology, College of Plant Protection, Shenyang Agricultural University, Shenyang, China
| | - Zihao Xia
- Liaoning Key Laboratory of Plant Pathology, College of Plant Protection, Shenyang Agricultural University, Shenyang, China
| | - Yuanhua Wu
- Liaoning Key Laboratory of Plant Pathology, College of Plant Protection, Shenyang Agricultural University, Shenyang, China
| |
Collapse
|
|
11
|
Singh D, Sharma S, Jose-Santhi J, Kalia D, Singh RK. Hormones regulate the flowering process in saffron differently depending on the developmental stage. FRONTIERS IN PLANT SCIENCE 2023; 14:1107172. [PMID: 36968363 PMCID: PMC10034077 DOI: 10.3389/fpls.2023.1107172] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/24/2022] [Accepted: 02/02/2023] [Indexed: 06/18/2023]
Abstract
Flowering in saffron is a highly complex process regulated by the synchronized action of environmental cues and endogenous signals. Hormonal regulation of flowering is a very important process controlling flowering in several plants, but it has not been studied in saffron. Flowering in saffron is a continual process completed in months with distinct developmental phases, mainly divided into flowering induction and flower organogenesis/formation. In the present study, we investigated how phytohormones affect the flowering process at different developmental stages. The results suggest that different hormones differentially affect flower induction and formation in saffron. The exogenous treatment of flowering competent corms with abscisic acid (ABA) suppressed both floral induction and flower formation, whereas some other hormones, like auxins (indole acetic acid, IAA) and gibberellic acid (GA), behaved contrarily at different developmental stages. IAA promoted flower induction, while GA suppressed it; however, GA promoted flower formation, whereas IAA suppressed it. Cytokinin (kinetin) treatment suggested its positive involvement in flower induction and flower formation. The expression analysis of floral integrator and homeotic genes suggests that ABA might suppress floral induction by suppressing the expression of the floral promoter (LFY, FT3) and promoting the expression of the floral repressor (SVP) gene. Additionally, ABA treatment also suppressed the expression of the floral homeotic genes responsible for flower formation. GA reduces the expression of flowering induction gene LFY, while IAA treatment upregulated its expression. In addition to these genes, a flowering repressor gene, TFL1-2, was also found to be downregulated in IAA treatment. Cytokinin promotes flowering induction by increasing the expression levels of the LFY gene and decreasing the TFL1-2 gene expression. Moreover, it improved flower organogenesis by increasing the expression of floral homeotic genes. Overall, the results suggest that hormones differently regulate flowering in saffron via regulating floral integrator and homeotic gene expression.
Collapse
Affiliation(s)
- Deepika Singh
- Biotechnology Division, Council of Scientific and Industrial Research (CSIR)-Institute of Himalayan Bioresource Technology, Palampur, HP, India
| | - Sahiba Sharma
- Biotechnology Division, Council of Scientific and Industrial Research (CSIR)-Institute of Himalayan Bioresource Technology, Palampur, HP, India
| | - Joel Jose-Santhi
- Biotechnology Division, Council of Scientific and Industrial Research (CSIR)-Institute of Himalayan Bioresource Technology, Palampur, HP, India
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India
| | - Diksha Kalia
- Biotechnology Division, Council of Scientific and Industrial Research (CSIR)-Institute of Himalayan Bioresource Technology, Palampur, HP, India
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India
| | - Rajesh Kumar Singh
- Biotechnology Division, Council of Scientific and Industrial Research (CSIR)-Institute of Himalayan Bioresource Technology, Palampur, HP, India
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India
| |
Collapse
|
|
12
|
Thabault M, Turpin V, Balado É, Fernandes-Gomes C, Huot AL, Cantereau A, Fernagut PO, Jaber M, Galvan L. Age-related behavioural and striatal dysfunctions in Shank3 ΔC/ΔC mouse model of autism spectrum disorder. Eur J Neurosci 2023; 57:607-618. [PMID: 36656446 DOI: 10.1111/ejn.15919] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2022] [Revised: 12/13/2022] [Accepted: 01/13/2023] [Indexed: 01/20/2023]
Abstract
Autism spectrum disorders (ASDs) are defined as a set of neurodevelopmental disorders and a lifelong condition. In mice, most of the studies focused on the developmental aspects of these diseases. In this paper, we examined the evolution of motor stereotypies through adulthood in the Shank3ΔC/ΔC mouse model of ASD, and their underlying striatal alterations, at 10 weeks, 20 weeks, and 40 weeks. We highlighted that motor stereotypies worsened at 40 weeks possibly carried by earlier striatal medium spiny neurons (MSN) alterations in GABAergic transmission and morphology. Moreover, we report that 20 weeks could be a critical time-point in the striatal-related ASD physiopathology, and we suggest that MSN alterations may not be the direct consequence of developmental issues, but rather be a consequence of other impairments occurring earlier.
Collapse
Affiliation(s)
- Mathieu Thabault
- Laboratoire de Neurosciences Expérimentales et Cliniques, Inserm, Université de Poitiers, Poitiers, France
| | - Valentine Turpin
- Laboratoire de Neurosciences Expérimentales et Cliniques, Inserm, Université de Poitiers, Poitiers, France
| | - Éric Balado
- Laboratoire de Neurosciences Expérimentales et Cliniques, Inserm, Université de Poitiers, Poitiers, France
| | - Cloé Fernandes-Gomes
- Laboratoire de Neurosciences Expérimentales et Cliniques, Inserm, Université de Poitiers, Poitiers, France
| | | | | | - Pierre-Olivier Fernagut
- Laboratoire de Neurosciences Expérimentales et Cliniques, Inserm, Université de Poitiers, Poitiers, France
| | - Mohamed Jaber
- Laboratoire de Neurosciences Expérimentales et Cliniques, Inserm, Université de Poitiers, Poitiers, France.,Centre Hospitalier Universitaire de Poitiers, Poitiers, France
| | - Laurie Galvan
- Laboratoire de Neurosciences Expérimentales et Cliniques, Inserm, Université de Poitiers, Poitiers, France
| |
Collapse
|
|
13
|
Li Y, Liu X, Liu X, Peng Y, Zhu B, Guo S, Wang C, Wang D, Li S. Transforming growth factor-β signalling pathway in tendon healing. Growth Factors 2022; 40:98-107. [PMID: 35707986 DOI: 10.1080/08977194.2022.2082294] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
Transforming growth factor-β(TGF-β) plays an important but diverse role in tendon injuries, such as collagen synthesis, cell proliferation, cell differentiation, and cell adhesion, leading to tendon healing and tendon fibrosis. In the well-known canonical TGF-β signalling pathway, TGF-β activates Smad signalling through its two cell surface receptors, which leads to Smad-mediated transcriptional regulation and is also regulated by inhibitory Smads, forming a negative feedback regulatory pathway. In the context of the canonical TGF-β signalling mechanism mediated by Smad, the activated receptors also send signals through other signal transducers, which in the backdrop of TGF-β signaling are collectively known as non-Smad signalling pathways. Activated TGF-β binds to the receptor and acts through these signalling pathways. Understanding the mechanism of the TGF-β signalling pathway and its role in tendon repair is of great significance for targeting the TGF-β signalling pathway to accelerate tendon healing and reduce tendon fibrosis.
Collapse
Affiliation(s)
- Yujie Li
- Institute of Physical Education, Southwest Medical University, Luzhou, Sichuan, China
| | - Xinyue Liu
- Institute of Physical Education, Southwest Medical University, Luzhou, Sichuan, China
| | - Xueli Liu
- Institute of Physical Education, Southwest Medical University, Luzhou, Sichuan, China
| | - Yuanqiu Peng
- Institute of Physical Education, Southwest Medical University, Luzhou, Sichuan, China
| | - Bin Zhu
- Institute of Physical Education, Southwest Medical University, Luzhou, Sichuan, China
| | - Sheng Guo
- Spinal Surgery Department, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan, China
| | - Chenglong Wang
- Spinal Surgery Department, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan, China
| | - Dingxuan Wang
- Institute of Physical Education, Southwest Medical University, Luzhou, Sichuan, China
| | - Sen Li
- Institute of Physical Education, Southwest Medical University, Luzhou, Sichuan, China
- Spinal Surgery Department, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan, China
| |
Collapse
|
|
14
|
Barua S, Jiang LI, Kononov T, Zahr AS. A Case Study Investigating the Short-Term Efficacy and Tolerability of a Daily Serum Composed from a Unique Sunflower Sprout Extract. J Cosmet Dermatol 2022; 21:4410-4421. [PMID: 35897147 DOI: 10.1111/jocd.15248] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2022] [Revised: 07/08/2022] [Accepted: 07/15/2022] [Indexed: 11/28/2022]
Abstract
BACKGROUND Fatigued skin, defined as dehydrated skin with lack of visual facial firmness and dull appearance, can be attributed to intrinsic and extrinsic factors of aging. An antiaging daily serum (AADS) containing a unique sunflower sprout extract (SSE) was formulated to target fatigued and photodamaged skin. AIMS Utilizing both preclinical and clinical testing models, the efficacy of the AADS was investigated to improve fatigued and photodamaged skin. PATIENTS/ METHOD Preclinical studies included in vitro analysis of adenosine triphosphate (ATP) production in fatigued dermal fibroblasts, inhibition of ultraviolet radiation A (UVA) induced advanced glycation end products (AGEs) in keratinocytes, and ex vivo gene expression after incubation with the SSE. An institutional review board (IRB)-approved short-term, 7-day, clinical case study was conducted in twenty-eight female subjects, Fitzpatrick skin type I-IV, aged 30 to 60 years with moderate overall photodamage and skin fatigue. This was a double-blinded, randomized, controlled, single-center case study testing the AADS alone and in combination with an anti-aging facial moisturizer (AAFM). RESULTS The SSE boosted intracellular ATP production in fatigued fibroblasts and reduced the formation of AGEs in keratinocytes. The SSE increased expression of genes related to epidermal keratinization and downregulated genes related to inflammation. Statistically significant improvement was found after 7-days of twice-daily use of the AADS alone and in combination with the AAFM. Products were well tolerated and perceived by subjects. CONCLUSION Preclinical results combined with the clinical results strongly suggest that the AADS containing the SSE was tolerable and effective in targeting fatigued and photodamaged skin.
Collapse
Affiliation(s)
- Sushmita Barua
- Department of Chemical Engineering, The Pennsylvania State University, University Park, PA, USA
| | | | | | | |
Collapse
|
|
15
|
Zero AM, Paris MT, Rice CL. Frequency dependent coexistence of muscle fatigue and potentiation assessed by concentric isotonic contractions in human plantar flexors. J Appl Physiol (1985) 2022; 133:490-505. [PMID: 35796610 DOI: 10.1152/japplphysiol.00214.2022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
The purpose was to investigate whether post-activation potentiation (PAP) mitigates power (i.e., torque x angular velocity) loss during dynamic fatiguing contractions and subsequent recovery by enhancing either muscle torque or angular velocity in human plantar flexors. In 12 participants, electrically stimulated (1, 10 and 50 Hz) dynamic contractions were done during a voluntary isotonic fatiguing protocol (20 and 50% voluntary decreases) until a 75% loss in voluntary peak power, and throughout 30 minutes of recovery. At the initial portion of fatigue (20% decrease), power responses of evoked low frequencies (1 and 10 Hz) were enhanced due to PAP (156 and 137%, respectively, P<0.001), while voluntary maximal efforts were depressed due to fatiguing mechanisms. Following the fatiguing task, prolonged low-frequency force depression (PLFFD) was evident by reduced 10:50 Hz peak power ratios (21 - 24%) from 3-min onwards during the 30-min recovery (P<0.005). Inducing PAP with maximal voluntary contractions during PLFFD enhanced the peak power responses of low frequencies (1 and 10 Hz) by 128 - 160 %, P<0.01. This PAP response mitigated the effects of PLFFD as the 1:50 (P<0.05) and 10:50 (P>0.4) Hz peak power ratios were greater or not different from the pre-fatigue values. Additionally, PAP enhanced peak torque more than peak angular velocity during both baseline and fatigue measurements (P<0.03). These results indicate that PAP can ameliorate PLFFD acutely when evaluated during concentric isotonic contractions and that peak torque is enhanced to a greater degree compared to peak angular velocity at baseline and in a fatigued state.
Collapse
Affiliation(s)
- Alexander M Zero
- School of Kinesiology, Faculty of Health Sciences, grid.39381.30Western University, London, ON, Canada
| | - Michael T Paris
- School of Kinesiology, Faculty of Health Sciences, grid.39381.30Western University, London, ON, Canada
| | - Charles L Rice
- Department of Anatomy and Cell Biology, grid.443228.bWestern University, London, Ontario, Canada
| |
Collapse
|
|
16
|
Iannetta D, Zhang J, Murias JM, Aboodarda SJ. Neuromuscular and perceptual mechanisms of fatigue accompanying task failure in response to moderate-, heavy-, severe-, and extreme-intensity cycling. J Appl Physiol (1985) 2022; 133:323-334. [PMID: 35771217 DOI: 10.1152/japplphysiol.00764.2021] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
A comprehensive characterization of neuromuscular and perceptual mechanisms of fatigue at task failure following exercise across the entire intensity spectrum is lacking. This study evaluated the extent of peripheral and central fatigue, and corresponding perceptual attributes, at task failure following cycling within the moderate-(MOD), heavy-(HVY), severe-(SVR), and extreme-(EXT) intensity domains. After a ramp-incremental test, eleven young males performed four constant-power output trials to the limit of tolerance (Tlim) at four distinct domain-specific workloads. These trials were preceded and followed by 5-s knee-extension maximal voluntary contractions (MVC) and femoral nerve electrical stimuli to quantify peripheral and central fatigue. Additionally, perceptual measures including ratings of global fatigue, legs pain, dyspnea and perceived effort (RPE) were also collected. At Tlim, reductions in MVC were independent of intensity (P>0.05). However, peripheral fatigue was greater following EXT and SVR and progressively, but distinctively, lower following HVY and MOD (P<0.05). Central fatigue was similar after SVR, HVY, and MOD, but absent after EXT (P<0.05). At Tlim, subjective ratings of global fatigue were progressively higher with lower exercise intensities, while ratings of legs pain and dyspnea were progressively higher with higher exercise intensities. On the other hand, RPE was maximal following HVY, SVR, and EXT, but not MOD. The findings demonstrate that at Tlim the extent of peripheral fatigue is highly domain-specific whereas the extent of central fatigue is not. Sensations such as fatigue, pain, and dyspnea may integrate with mechanisms of sense of effort to determine task failure in a manner specific to each intensity domain.
Collapse
Affiliation(s)
- Danilo Iannetta
- Faculty of Kinesiology, University of Calgary, Calgary, Alberta, Canada
| | - Jenny Zhang
- Faculty of Kinesiology, University of Calgary, Calgary, Alberta, Canada
| | - Juan M Murias
- Faculty of Kinesiology, University of Calgary, Calgary, Alberta, Canada
| | | |
Collapse
|
|
17
|
Yasmeen N, Datta M, Kumar V, Alshehri FS, Almalki AH, Haque S. Deciphering the Link Between ERUPR Signaling and MicroRNA in Pathogenesis of Alzheimer’s Disease. Front Aging Neurosci 2022; 14:880167. [PMID: 35615589 PMCID: PMC9126300 DOI: 10.3389/fnagi.2022.880167] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2022] [Accepted: 03/23/2022] [Indexed: 12/13/2022] Open
Abstract
Alzheimer’s disease (AD) is a neurodegenerative proteinopathic disease. The deposits of misfolded Amyloid β and Tau proteins in the brain of patients with AD suggest an imbalance in endoplasmic reticulum (ER) proteostasis. ER stress is due to accumulation of aberrant proteins in the ER lumen, which then leads to activation of three sensor protein pathways that ultimately evokes the adaptive mechanism of the unfolded protein response (UPR). The UPR mechanism operates via adaptive UPR and the apoptotic UPR. Adaptive UPR tries to restore imbalance in ER hemostasis by decreasing protein production, enhanced chaperone involvement to restore protein folding, misfolded protein decay by proteasome, and suppression of ribosomal translation ultimately relieving the excessive protein load in the ER. Subsequently, apoptotic UPR activated under severe ER stress conditions triggers cell death. MicroRNAs (miRNAs) are small non-coding protein causing dysregulated translational of mRNAs in a sequential manner. They are considered to be critical elements in the maintenance of numerous cellular activities, hemostasis, and developmental processes. Therefore, upregulation or downregulation of miRNA expression is implicated in several pathogenic processes. Evidence from scientific studies suggest a strong correlation between ERUPR signaling and miRNA dysregulation but the research done is still dormant. In this review, we summarized the cross-talk between ER stress, and the UPR signaling processes and their role in AD pathology by scrutinizing and collecting information from original research and review articles.
Collapse
Affiliation(s)
- Nusrath Yasmeen
- Amity Institute of Biotechnology, Amity University Rajasthan, Jaipur, India
| | - Manali Datta
- Amity Institute of Biotechnology, Amity University Rajasthan, Jaipur, India
| | - Vikram Kumar
- Amity Institute of Biotechnology, Amity University Rajasthan, Jaipur, India
- *Correspondence: Vikram Kumar, ;
| | - Fahad S. Alshehri
- Department of Pharmacology and Toxicology, College of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia
| | - Atiah H. Almalki
- Department of Pharmaceutical Chemistry, College of Pharmacy, Taif University, Taif, Saudi Arabia
- Addiction and Neuroscience Research Unit, College of Pharmacy, Taif University, Taif, Saudi Arabia
| | - Shafiul Haque
- Research and Scientific Studies Unit, College of Nursing and Allied Health Sciences, Jazan University, Jazan, Saudi Arabia
- Faculty of Medicine, Bursa Uludağ University, Bursa, Turkey
| |
Collapse
|
|
18
|
Pradhan S, Gao R, Bush K, Zhang N, Wairkar YP, Sarkar PS. Polyglutamine Expansion in Huntingtin and Mechanism of DNA Damage Repair Defects in Huntington’s Disease. Front Cell Neurosci 2022; 16:837576. [PMID: 35444517 PMCID: PMC9013776 DOI: 10.3389/fncel.2022.837576] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Accepted: 02/07/2022] [Indexed: 12/27/2022] Open
Abstract
Emerging evidence suggests that DNA repair deficiency and genome instability may be the impending signs of many neurological diseases. Genome-wide association (GWAS) studies have established a strong correlation between genes that play a role in DNA damage repair and many neurodegenerative diseases, including Huntington’s disease (HD), and several other trinucleotides repeat expansion-related hereditary ataxias. Recently, many reports have documented a significant role played by the DNA repair processes in aging and in modifying many neurodegenerative diseases, early during their progression. Studies from our lab and others have now begun to understand the mechanisms that cause defective DNA repair in HD and surprisingly, many proteins that have a strong link to known neurodegenerative diseases seem to be important players in these cellular pathways. Mutations in huntingtin (HTT) gene that lead to polyglutamine repeat expansion at the N-terminal of HTT protein has been shown to disrupt transcription-coupled DNA repair process, a specialized DNA repair process associated with transcription. Due to the recent progress made in understanding the mechanisms of DNA repair in relation to HD, in this review, we will mainly focus on the mechanisms by which the wild-type huntingtin (HTT) protein helps in DNA repair during transcription, and the how polyglutamine expansions in HTT impedes this process in HD. Further studies that identify new players in DNA repair will help in our understanding of this process in neurons. Furthermore, it should help us understand how various DNA repair mechanism(s) coordinate to maintain the normal physiology of neurons, and provide insights for the development of novel drugs at prodromal stages of these neurodegenerative diseases.
Collapse
Affiliation(s)
- Subrata Pradhan
- Department of Neurology, University of Texas Medical Branch, Galveston, TX, United States
| | - Rui Gao
- Department of Neurology, University of Texas Medical Branch, Galveston, TX, United States
| | - Keegan Bush
- Department of Neuroscience, Cell Biology and Anatomy, University of Texas Medical Branch, Galveston, TX, United States
| | - Nan Zhang
- Department of Neurology, Houston Methodist Research Institute, Houston, TX, United States
| | - Yogesh P. Wairkar
- Department of Neurology, University of Texas Medical Branch, Galveston, TX, United States
- Department of Neuroscience, Cell Biology and Anatomy, University of Texas Medical Branch, Galveston, TX, United States
| | - Partha S. Sarkar
- Department of Neurology, University of Texas Medical Branch, Galveston, TX, United States
- Department of Neuroscience, Cell Biology and Anatomy, University of Texas Medical Branch, Galveston, TX, United States
- *Correspondence: Partha S. Sarkar,
| |
Collapse
|
|
19
|
Zhang R, Yong VW, Xue M. Revisiting Minocycline in Intracerebral Hemorrhage: Mechanisms and Clinical Translation. Front Immunol 2022; 13:844163. [PMID: 35401553 PMCID: PMC8993500 DOI: 10.3389/fimmu.2022.844163] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2021] [Accepted: 02/24/2022] [Indexed: 01/31/2023] Open
Abstract
Intracerebral hemorrhage (ICH) is an important subtype of stroke with an unsatisfactory prognosis of high mortality and disability. Although many pre-clinical studies and clinical trials have been performed in the past decades, effective therapy that meaningfully improve prognosis and outcomes of ICH patients is still lacking. An active area of research is towards alleviating secondary brain injury after ICH through neuroprotective pharmaceuticals and in which minocycline is a promising candidate. Here, we will first discuss new insights into the protective mechanisms of minocycline for ICH including reducing iron-related toxicity, maintenance of blood-brain barrier, and alleviating different types of cell death from preclinical data, then consider its shortcomings. Finally, we will review clinical trial perspectives for minocycline in ICH. We hope that this summary and discussion about updated information on minocycline as a viable treatment for ICH can facilitate further investigations.
Collapse
Affiliation(s)
- Ruiyi Zhang
- The Departments of Cerebrovascular Diseases, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Henan Medical Key Laboratory of Translational Cerebrovascular Diseases, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada
- Department of Clinical Neurosciences, University of Calgary, Calgary, AB, Canada
| | - V. Wee Yong
- Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada
- Department of Clinical Neurosciences, University of Calgary, Calgary, AB, Canada
| | - Mengzhou Xue
- The Departments of Cerebrovascular Diseases, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Henan Medical Key Laboratory of Translational Cerebrovascular Diseases, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| |
Collapse
|
|
20
|
Park SJ, Joo SH, Lee N, Jang WJ, Seo JH, Jeong CH. ACY-241, an HDAC6 inhibitor, overcomes erlotinib resistance in human pancreatic cancer cells by inducing autophagy. Arch Pharm Res 2021; 44:1062-1075. [PMID: 34761352 DOI: 10.1007/s12272-021-01359-x] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2021] [Accepted: 11/01/2021] [Indexed: 10/19/2022]
Abstract
Histone deacetylase 6 (HDAC6) is a promising target for cancer treatment because it regulates cell mobility, protein trafficking, cell growth, apoptosis, and metastasis. However, the mechanism of HDAC6-induced anticancer drug resistance is unclear. In this study, we evaluated the anticancer effect of ACY-241, an HDAC6-selective inhibitor, on erlotinib-resistant pancreatic cancer cells that overexpress HDAC6. Our data revealed that ACY-241 hyperacetylated the HDAC6 substrate, α-tubulin, leading to a significant reduction in cell viability of erlotinib-resistant pancreatic cells, BxPC3-ER and HPAC-ER. Notably, a synergistic anticancer effect was observed in cells that received combined treatment with ACY-241 and erlotinib. Combined treatment effectively induced autophagy and inhibited autophagy through siLC3B, and siATG5 alleviated ACY-241-mediated cell death, as reflected by the recovery of PARP cleavage and apoptosis rates. In addition, combined ACY-241 and erlotinib treatment induced autophagy and subsequently, cell death by reducing AKT-mTOR activity and increasing phospho-AMPK signaling. Therefore, HDAC6 may be involved in the suppression of autophagy and acquisition of resistance to erlotinib in ER pancreatic cancer cells. ACY-241 to overcome erlotinib resistance could be an effective therapeutic strategy against pancreatic cancer.
Collapse
Affiliation(s)
- Seong-Jun Park
- College of Pharmacy, Keimyung University, 1095 Dalgubeil-daero, Daegu, 42601, South Korea
| | - Sang Hoon Joo
- Department of Pharmacy, Daegu Catholic University, Gyeongsan, 38430, South Korea
| | - Naeun Lee
- College of Pharmacy, Keimyung University, 1095 Dalgubeil-daero, Daegu, 42601, South Korea
| | - Won-Jun Jang
- College of Pharmacy, Keimyung University, 1095 Dalgubeil-daero, Daegu, 42601, South Korea
| | - Ji Hae Seo
- Department of Biochemistry, Keimyung University School of Medicine, 1095 Dalgubeil-daero, Daegu, 42601, South Korea.
| | - Chul-Ho Jeong
- College of Pharmacy, Keimyung University, 1095 Dalgubeil-daero, Daegu, 42601, South Korea.
| |
Collapse
|
|
21
|
Paul S, Roy D, Pati S, Sa G. The Adroitness of Andrographolide as a Natural Weapon Against Colorectal Cancer. Front Pharmacol 2021; 12:731492. [PMID: 34795581 PMCID: PMC8592893 DOI: 10.3389/fphar.2021.731492] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2021] [Accepted: 09/28/2021] [Indexed: 12/15/2022] Open
Abstract
The conventional carcinoma treatment generally encompasses the employment of radiotherapy, chemotherapy, surgery or use of cytotoxic drugs. However, recent advances in pharmacological research have divulged the importance of traditional treatments in cancer. The aim of the present review is to provide an overview of the importance of one such medicinal herb of Chinese and Indian origin: Andrographis paniculate on colorectal cancer with special emphasis on its principal bioactive component andrographolide (AGP) and its underlying mechanisms of action. AGP has long been known to possess medicinal properties. Studies led by numerous groups of researchers shed light on its molecular mechanism of action. AGP has been shown to act in a multi-faceted manner in context of colorectal cancer by targeting matrix metalloproteinase-9, Toll-like receptor or NFκB signaling pathways. In this review, we highlighted the recent studies that show that AGP can act as an effective immunomodulator by harnessing effective anti-tumor immune response. Recent studies strongly recommend further research on this compound and its analogues, especially under in-vivo condition to assess its actual potential as a prospective and efficient candidate against colorectal cancer. The current review deals with the roles of this phytomedicine in context of colorectal cancer and briefly describes its perspectives to emerge as an essential anti-cancer drug candidate. Finally, we also point out the drawbacks and difficulties in administration of AGP and indicate the use of nano-formulations of this phytomedicine for better therapeutic efficacy.
Collapse
Affiliation(s)
- Silpita Paul
- Division of Molecular Medicine, Bose Institute, Kolkata, India
| | - Dia Roy
- Division of Molecular Medicine, Bose Institute, Kolkata, India
| | - Subhadip Pati
- Division of Molecular Medicine, Bose Institute, Kolkata, India
| | - Gaurisankar Sa
- Division of Molecular Medicine, Bose Institute, Kolkata, India
| |
Collapse
|
|
22
|
Yuan B, Ma B, Yu J, Meng Q, Du T, Li H, Zhu Y, Sun Z, Ma S, Song C. Fecal Bacteria as Non-Invasive Biomarkers for Colorectal Adenocarcinoma. Front Oncol 2021; 11:664321. [PMID: 34447694 PMCID: PMC8383742 DOI: 10.3389/fonc.2021.664321] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2021] [Accepted: 06/07/2021] [Indexed: 12/14/2022] Open
Abstract
Colorectal adenocarcinoma (CRC) ranks one of the five most lethal malignant tumors both in China and worldwide. Early diagnosis and treatment of CRC could substantially increase the survival rate. Emerging evidence has revealed the importance of gut microbiome on CRC, thus fecal microbial community could be termed as a potential screen for non-invasive diagnosis. Importantly, few numbers of bacteria genus as non-invasive biomarkers with high sensitivity and specificity causing less cost would be benefitted more in clinical compared with the whole microbial community analysis. Here we analyzed the gut microbiome between CRC patients and healthy people using 16s rRNA sequencing showing the divergence of microbial composition between case and control. Furthermore, ExtraTrees classifier was performed for the classification of CRC gut microbiome and heathy control, and 13 bacteria were screened as biomarkers for CRC. In addition, 13 biomarkers including 12 bacteria genera and FOBT showed an outstanding sensitivity and specificity for discrimination of CRC patients from healthy controls. This method could be used as a non-invasive method for CRC early diagnosis.
Collapse
Affiliation(s)
- Biao Yuan
- Department of Gastroenterological Surgery, Shanghai East Hospital, Tongji University of Medicine, Shanghai, China
| | - Bin Ma
- Department of Colorectal Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, China
| | - Jing Yu
- Research and Development Department, Shanghai Personal Biotechnology Co., Ltd, Shanghai, China.,ECNU-PERSONAL Joint Laboratory of Genetic Detection and Application, Shanghai Personal Biotechnology Co., Ltd, Shanghai, China
| | - Qingkai Meng
- Department of Colorectal Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, China
| | - Tao Du
- Department of Gastroenterological Surgery, Shanghai East Hospital, Tongji University of Medicine, Shanghai, China
| | - Hongyi Li
- Research and Development Department, Shanghai Personal Biotechnology Co., Ltd, Shanghai, China
| | - Yueyan Zhu
- Research and Development Department, Shanghai Personal Biotechnology Co., Ltd, Shanghai, China
| | - Zikui Sun
- Research and Development Department, Shanghai Personal Biotechnology Co., Ltd, Shanghai, China.,ECNU-PERSONAL Joint Laboratory of Genetic Detection and Application, Shanghai Personal Biotechnology Co., Ltd, Shanghai, China
| | - Siping Ma
- Department of Colorectal Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, China
| | - Chun Song
- Department of Gastroenterological Surgery, Shanghai East Hospital, Tongji University of Medicine, Shanghai, China
| |
Collapse
|
|
23
|
Stacchiotti A, Corsetti G. Natural Compounds and Autophagy: Allies Against Neurodegeneration. Front Cell Dev Biol 2020; 8:555409. [PMID: 33072744 PMCID: PMC7536349 DOI: 10.3389/fcell.2020.555409] [Citation(s) in RCA: 55] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2020] [Accepted: 09/01/2020] [Indexed: 12/12/2022] Open
Abstract
Prolonging the healthy life span and limiting neurological illness are imperative goals in gerontology. Age-related neurodegeneration is progressive and leads to severe diseases affecting motility, memory, cognitive function, and social life. To date, no effective treatments are available for neurodegeneration and irreversible neuronal loss. Bioactive phytochemicals could represent a natural alternative to ensure active aging and slow onset of neurodegenerative diseases in elderly patients. Autophagy or macroautophagy is an evolutionarily conserved clearing process that is needed to remove aggregate-prone proteins and organelles in neurons and glia. It also is crucial in synaptic plasticity. Aberrant autophagy has a key role in aging and neurodegeneration. Recent evidence indicates that polyphenols like resveratrol and curcumin, flavonoids, like quercetin, polyamine, like spermidine and sugars, like trehalose, limit brain damage in vitro and in vivo. Their common mechanism of action leads to restoration of efficient autophagy by dismantling misfolded proteins and dysfunctional mitochondria. This review focuses on the role of dietary phytochemicals as modulators of autophagy to fight Alzheimer's and Parkinson's diseases, fronto-temporal dementia, amyotrophic lateral sclerosis, and psychiatric disorders. Currently, most studies have involved in vitro or preclinical animal models, and the therapeutic use of phytochemicals in patients remains limited.
Collapse
Affiliation(s)
- Alessandra Stacchiotti
- Division of Anatomy and Physiopathology, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.,Interdepartmental University Center of Research "Adaptation and Regeneration of Tissues and Organs (ARTO)," University of Brescia, Brescia, Italy
| | - Giovanni Corsetti
- Division of Anatomy and Physiopathology, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy
| |
Collapse
|
|
24
|
Prahlad V. The discovery and consequences of the central role of the nervous system in the control of protein homeostasis. J Neurogenet 2020; 34:489-499. [PMID: 32527175 PMCID: PMC7736053 DOI: 10.1080/01677063.2020.1771333] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2020] [Accepted: 05/14/2020] [Indexed: 12/30/2022]
Abstract
Organisms function despite wide fluctuations in their environment through the maintenance of homeostasis. At the cellular level, the maintenance of proteins as functional entities at target expression levels is called protein homeostasis (or proteostasis). Cells implement proteostasis through universal and conserved quality control mechanisms that surveil and monitor protein conformation. Recent studies that exploit the powerful ability to genetically manipulate specific neurons in C. elegans have shown that cells within this metazoan lose their autonomy over this fundamental survival mechanism. These studies have uncovered novel roles for the nervous system in controlling how and when cells activate their protein quality control mechanisms. Here we discuss the conceptual underpinnings, experimental evidence and the possible consequences of such a control mechanism. PRELUDE: Whether the detailed examination of parts of the nervous system and their selective perturbation is sufficient to reconstruct how the brain generates behavior, mental disease, music and religion remains an open question. Yet, Sydney Brenner's development of C. elegans as an experimental organism and his faith in the bold reductionist approach that 'the understanding of wild-type behavior comes best after the discovery and analysis of mutations that alter it', has led to discoveries of unexpected roles for neurons in the biology of organisms.
Collapse
Affiliation(s)
- Veena Prahlad
- Department of Biology, Aging Mind and Brain Initiative, University of Iowa, Iowa City, IA, USA
- Iowa Neuroscience Institute, University of Iowa, Iowa City, IA, USA
| |
Collapse
|
|
25
|
Yan G, Li D, Zhong X, Liu G, Wang X, Lu Y, Qin F, Guo Y, Duan S, Li D. Identification of HDAC6 selective inhibitors: pharmacophore based virtual screening, molecular docking and molecular dynamics simulation. J Biomol Struct Dyn 2020; 39:1928-1939. [PMID: 32178584 DOI: 10.1080/07391102.2020.1743760] [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] [Indexed: 02/08/2023]
Abstract
HDAC6 regulates the expression and activity of various tumor-related proteins, but currently there is no selective inhibitor targeting HDAC6 for clinical application. In order to discover novel HDAC6 inhibitors, virtual screening methods comprised of pharmacophore based virtual screening, molecular docking and molecular dynamics (MD) simulations were employed. 15 molecules were obtained after virtual screening. After in vitro bioassays, two of the hits showed inhibition activity against HDAC6, among which the inhibition activity of G1 to HDAC6 reached 81% at concentration of 20 μM. In addition, the inhibitory activity against HDAC1 and HDAC10 demonstrated that G1 and G10 were highly selective to HDAC6. The analysis of the binding modes of G1 and G10 provides a reference for further development of highly active HDAC6 inhibitors. Communicated by Ramaswamy H. Sarma.
Collapse
Affiliation(s)
- Guoyi Yan
- Henan Provincial People's Hospital, Zhengzhou, Henan, China.,School of Clinical Medicine, Henan University, Zhengzhou, China
| | - Dongxiao Li
- Department of Gastroenterology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xinxin Zhong
- State Key Laboratory of Biotherapy, Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University, Sichuan, China
| | - Ge Liu
- Henan Provincial People's Hospital, Zhengzhou, Henan, China.,School of Clinical Medicine, Henan University, Zhengzhou, China
| | - Xueqin Wang
- Henan Provincial People's Hospital, Zhengzhou, Henan, China.,College of Bioengineering, Henan University of Technology, Zhengzhou, China
| | - Yuanxiang Lu
- Henan Provincial People's Hospital, Zhengzhou, Henan, China.,School of Clinical Medicine, Henan University, Zhengzhou, China
| | - Fangyuan Qin
- Henan Provincial People's Hospital, Zhengzhou, Henan, China.,School of Clinical Medicine, Henan University, Zhengzhou, China
| | - Yuqi Guo
- Henan Provincial People's Hospital, Zhengzhou, Henan, China.,School of Clinical Medicine, Henan University, Zhengzhou, China
| | - Shaofeng Duan
- School of Pharmacy, Henan University, Kaifeng, China
| | - Deyu Li
- Henan Provincial People's Hospital, Zhengzhou, Henan, China.,School of Clinical Medicine, Henan University, Zhengzhou, China
| |
Collapse
|
|
26
|
Mora-Navarro C, Badileanu A, Gracioso Martins AM, Ozpinar EW, Gaffney L, Huntress I, Harrell E, Enders JR, Peng X, Branski RC, Freytes DO. Porcine Vocal Fold Lamina Propria-Derived Biomaterials Modulate TGF-β1-Mediated Fibroblast Activation in Vitro. ACS Biomater Sci Eng 2020; 6:1690-1703. [PMID: 33455360 DOI: 10.1021/acsbiomaterials.9b01837] [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: 01/12/2023]
Abstract
The vocal fold lamina propria (VFLP), one of the outermost layers of the vocal fold (VF), is composed of tissue-specific extracellular matrix (ECM) proteins and is highly susceptible to injury. Various biomaterials have been clinically tested to treat voice disorders (e.g., hydrogels, fat, and hyaluronic acid), but satisfactory recovery of the VF functionality remains elusive. Fibrosis or scar formation in the VF is a major challenge, and the development and refinement of novel therapeutics that promote the healing and normal function of the VF are needed. Injectable hydrogels derived from native tissues have been previously reported with major advantages over synthetic hydrogels, including constructive tissue remodeling and reduced scar tissue formation. This study aims to characterize the composition of a decellularized porcine VFLP-ECM scaffold and the cytocompatibility and potential antifibrotic properties of a hydrogel derived from VFLP-ECM. In addition, we isolated potential matrix-bound vesicles (MBVs) and macromolecules from the VFLP-ECM that also downregulated smooth muscle actin ACTA2 under transforming growth factor-beta 1 (TGF-β1) stimulation. The results provide evidence of the unique protein composition of the VFLP-ECM and the potential link between the components of the VFLP-ECM and the inhibition of TGF-β1 signaling observed in vitro when transformed into injectable forms.
Collapse
Affiliation(s)
- Camilo Mora-Navarro
- Joint Department of Biomedical Engineering, North Carolina State University/ University of North Carolina-Chapel Hill, Raleigh, North Carolina 27695, United States.,Comparative Medicine Institute, North Carolina State University, Raleigh, North Carolina 27695, United States
| | - Andreea Badileanu
- Joint Department of Biomedical Engineering, North Carolina State University/ University of North Carolina-Chapel Hill, Raleigh, North Carolina 27695, United States.,Comparative Medicine Institute, North Carolina State University, Raleigh, North Carolina 27695, United States
| | - Ana M Gracioso Martins
- Joint Department of Biomedical Engineering, North Carolina State University/ University of North Carolina-Chapel Hill, Raleigh, North Carolina 27695, United States.,Comparative Medicine Institute, North Carolina State University, Raleigh, North Carolina 27695, United States
| | - Emily W Ozpinar
- Joint Department of Biomedical Engineering, North Carolina State University/ University of North Carolina-Chapel Hill, Raleigh, North Carolina 27695, United States.,Comparative Medicine Institute, North Carolina State University, Raleigh, North Carolina 27695, United States
| | - Lewis Gaffney
- Joint Department of Biomedical Engineering, North Carolina State University/ University of North Carolina-Chapel Hill, Raleigh, North Carolina 27695, United States.,Comparative Medicine Institute, North Carolina State University, Raleigh, North Carolina 27695, United States
| | - Ian Huntress
- Department of Molecular Biomedical Sciences, North Carolina State University, Raleigh, North Carolina 27695, United States
| | - Erin Harrell
- Department of Molecular Biomedical Sciences, North Carolina State University, Raleigh, North Carolina 27695, United States
| | - Jeffrey R Enders
- Molecular Education, Technology and Research Innovation Center, North Carolina State University, Raleigh, North Carolina 27695, United States
| | - Xinxia Peng
- Department of Molecular Biomedical Sciences, North Carolina State University, Raleigh, North Carolina 27695, United States.,Bioinformatics Research Center, North Carolina State University, Raleigh, North Carolina 27695, United States
| | - Ryan C Branski
- NYU Voice Center, Department of Otolaryngology-Head and Neck Surgery, New York University School of Medicine, New York, New York 10016-6402, United States
| | - Donald O Freytes
- Joint Department of Biomedical Engineering, North Carolina State University/ University of North Carolina-Chapel Hill, Raleigh, North Carolina 27695, United States.,Comparative Medicine Institute, North Carolina State University, Raleigh, North Carolina 27695, United States
| |
Collapse
|
|
27
|
Zhao L, Ouyang Y, Li Q, Zhang Z. Modulation of p53 N-terminal transactivation domain 2 conformation ensemble and kinetics by phosphorylation. J Biomol Struct Dyn 2019; 38:2613-2623. [DOI: 10.1080/07391102.2019.1637784] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Affiliation(s)
- Likun Zhao
- College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China
| | - Yanhua Ouyang
- College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China
| | - Qian Li
- College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China
| | - Zhuqing Zhang
- College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China
| |
Collapse
|
|
28
|
EL Tallawy HNA, Farghaly WMA, El Hamed MA, Badry R, Usama K, Shehata GA, Tohamy AM, Abdulghani KO, Ghanem MK, Sayed MA, Yousef AH, Hashem HS, Rageh TA. Prevalence of Alzheimer dementia in Upper Egypt (desert areas). THE EGYPTIAN JOURNAL OF NEUROLOGY, PSYCHIATRY AND NEUROSURGERY 2019. [DOI: 10.1186/s41983-019-0074-y] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023] Open
|
|
29
|
Sun H, Xu F, Guo X, Wu D, Zhang X, Lou M, Luo F, Zhao Q, Xu G, Zhang Y. A Strigolactone Signal Inhibits Secondary Lateral Root Development in Rice. FRONTIERS IN PLANT SCIENCE 2019; 10:1527. [PMID: 31824543 PMCID: PMC6882917 DOI: 10.3389/fpls.2019.01527] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/12/2019] [Accepted: 11/01/2019] [Indexed: 05/21/2023]
Abstract
Strigolactones (SLs) and their derivatives are plant hormones that have recently been identified as regulators of primary lateral root (LR) development. However, whether SLs mediate secondary LR production in rice (Oryza sativa L.), and how SLs and auxin interact in this process, remain unclear. In this study, the SL-deficient (dwarf10) and SL-insensitive (dwarf3) rice mutants and lines overexpressing OsPIN2 (OE) were used to investigate secondary LR development. The effects of exogenous GR24 (a synthetic SL analogue), 1-naphthylacetic acid (NAA; an exogenous auxin), 1-naphthylphthalamic acid (NPA; a polar auxin transport inhibitor), and abamine (a synthetic SL inhibitor) on rice secondary LR development were investigated. Rice d mutants with impaired SL biosynthesis and signaling exhibited increased secondary LR production compared with wild-type (WT) plants. Application of GR24 decreased the numbers of secondary LRs in dwarf10 (d10) plants but not in dwarf3 (d3), plants. These results indicate that SLs negatively regulate rice secondary LR production. Higher expression of DR5::GUS and more secondary LR primordia were found in the d mutants than in the WT plants. Exogenous NAA application increased expression of DR5::GUS in the WT, but had no effect on secondary LR formation. No secondary LRs were recorded in the OE lines, although DR5::GUS levels were higher than in the WT plants. However, on application of NPA, the numbers of secondary LRs were reduced in d10 and d3 mutants. Application of NAA increased the number of secondary LRs in the d mutants. GR24 eliminated the effect of NAA on secondary LR development in the d10, but not in the d3, mutants. These results demonstrate the importance of auxin in secondary LR formation, and that this process is inhibited by SLs via the D3 response pathway, but the interaction between auxin and SLs is complex.
Collapse
Affiliation(s)
- Huwei Sun
- Laboratory of Rice Biology in Henan Province, Collaborative Innovation Center of Henan Grain Crops, College of Agronomy, Henan Agricultural University, Zhengzhou, China
- *Correspondence: Huwei Sun, ; Yali Zhang,
| | - Fugui Xu
- Laboratory of Rice Biology in Henan Province, Collaborative Innovation Center of Henan Grain Crops, College of Agronomy, Henan Agricultural University, Zhengzhou, China
| | - Xiaoli Guo
- Laboratory of Rice Biology in Henan Province, Collaborative Innovation Center of Henan Grain Crops, College of Agronomy, Henan Agricultural University, Zhengzhou, China
| | - Daxia Wu
- Key Laboratory of Plant Nutrition and Fertilization in Low-Middle Reaches of the Yangtze River, Ministry of Agriculture, Nanjing Agricultural University, Nanjing, China
| | - Xuhong Zhang
- Key Laboratory of Plant Nutrition and Fertilization in Low-Middle Reaches of the Yangtze River, Ministry of Agriculture, Nanjing Agricultural University, Nanjing, China
| | - Manman Lou
- Key Laboratory of Plant Nutrition and Fertilization in Low-Middle Reaches of the Yangtze River, Ministry of Agriculture, Nanjing Agricultural University, Nanjing, China
| | - Feifei Luo
- Key Laboratory of Plant Nutrition and Fertilization in Low-Middle Reaches of the Yangtze River, Ministry of Agriculture, Nanjing Agricultural University, Nanjing, China
| | - Quanzhi Zhao
- Laboratory of Rice Biology in Henan Province, Collaborative Innovation Center of Henan Grain Crops, College of Agronomy, Henan Agricultural University, Zhengzhou, China
| | - Guohua Xu
- Key Laboratory of Plant Nutrition and Fertilization in Low-Middle Reaches of the Yangtze River, Ministry of Agriculture, Nanjing Agricultural University, Nanjing, China
| | - Yali Zhang
- Key Laboratory of Plant Nutrition and Fertilization in Low-Middle Reaches of the Yangtze River, Ministry of Agriculture, Nanjing Agricultural University, Nanjing, China
- *Correspondence: Huwei Sun, ; Yali Zhang,
| |
Collapse
|
|
30
|
Costa-Silva TA, Flores-Santos JC, Freire RKB, Vitolo M, Pessoa-Jr A. Microbial cell disruption methods for efficient release of enzyme L-asparaginase. Prep Biochem Biotechnol 2018; 48:707-717. [DOI: 10.1080/10826068.2018.1487850] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/28/2022]
Affiliation(s)
- Tales A. Costa-Silva
- Department of Pharmaceutical and Biochemical Technology, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil
| | - Juan Carlos Flores-Santos
- Department of Pharmaceutical and Biochemical Technology, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil
| | - Rominne K. B. Freire
- Department of Pharmaceutical and Biochemical Technology, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil
| | - Michele Vitolo
- Department of Pharmaceutical and Biochemical Technology, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil
| | - Adalberto Pessoa-Jr
- Department of Pharmaceutical and Biochemical Technology, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil
| |
Collapse
|
|
31
|
Dutto I, Scalera C, Prosperi E. CREBBP and p300 lysine acetyl transferases in the DNA damage response. Cell Mol Life Sci 2018; 75:1325-1338. [PMID: 29170789 PMCID: PMC11105205 DOI: 10.1007/s00018-017-2717-4] [Citation(s) in RCA: 64] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2017] [Revised: 11/16/2017] [Accepted: 11/20/2017] [Indexed: 12/21/2022]
Abstract
The CREB-binding protein (CREBBP, or in short CBP) and p300 are lysine (K) acetyl transferases (KAT) belonging to the KAT3 family of proteins known to modify histones, as well as non-histone proteins, thereby regulating chromatin accessibility and transcription. Previous studies have indicated a tumor suppressor function for these enzymes. Recently, they have been found to acetylate key factors involved in DNA replication, and in different DNA repair processes, such as base excision repair, nucleotide excision repair, and non-homologous end joining. The growing list of CBP/p300 substrates now includes factors involved in DNA damage signaling, and in other pathways of the DNA damage response (DDR). This review will focus on the role of CBP and p300 in the acetylation of DDR proteins, and will discuss how this post-translational modification influences their functions at different levels, including catalytic activity, DNA binding, nuclear localization, and protein turnover. In addition, we will exemplify how these functions may be necessary to efficiently coordinate the spatio-temporal response to DNA damage. CBP and p300 may contribute to genome stability by fine-tuning the functions of DNA damage signaling and DNA repair factors, thereby expanding their role as tumor suppressors.
Collapse
Affiliation(s)
- Ilaria Dutto
- Istituto di Genetica Molecolare del CNR, Via Abbiategrasso 207, 27100, Pavia, Italy
- IRB, Carrer Baldiri Reixac 10, 08028, Barcelona, Spain
| | - Claudia Scalera
- Istituto di Genetica Molecolare del CNR, Via Abbiategrasso 207, 27100, Pavia, Italy
| | - Ennio Prosperi
- Istituto di Genetica Molecolare del CNR, Via Abbiategrasso 207, 27100, Pavia, Italy.
| |
Collapse
|
|
32
|
Barreca D, Currò M, Bellocco E, Ficarra S, Laganà G, Tellone E, Laura Giunta M, Visalli G, Caccamo D, Galtieri A, Ientile R. Neuroprotective effects of phloretin and its glycosylated derivative on rotenone-induced toxicity in human SH-SY5Y neuronal-like cells. Biofactors 2017; 43:549-557. [PMID: 28401997 DOI: 10.1002/biof.1358] [Citation(s) in RCA: 47] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2016] [Revised: 02/08/2017] [Accepted: 02/19/2017] [Indexed: 12/31/2022]
Abstract
Phloretin and phlorizin are the two strong natural antioxidants whose biological and pharmacological applications are rapidly growing in different human pathological conditions. The neuroprotective activity of the two flavonoids has been analyzed on cell culture of neuroblastoma cells. The neuroprotective activity of the two flavonoids has been analyzed on cell culture of neuroblastoma cells and evaluated by testing cell vitality, mitochondrial transmembrane potential and ROS production, antioxidant enzymes detection, activation of caspase 3, DNA damage, protein carbonylation, lipid peroxidation, and superoxide anion scavenging activity. Incubation of cells with rotenone caused cell death and significant increase in intracellular reactive oxygen species, activation of caspase 3, and variation in mitochondrial transmembrane potential. Although, rotenone exposure caused a significant increase of antioxidant enzymes, high levels of lipid peroxidation were also observed. Phloretin or phlorizin, at micromolar concentration, reduced rotenone-induced cell death by scavenging ability against superoxide anion radical, one of the main effectors of rotenone toxicity at level of mitochondrial respiratory chain complex I. Under our experimental conditions, a reduction of the intracellular ROS levels with consequent normalization of the aforementioned antioxidant enzymes occurred. Concomitantly, we observed the inhibition of caspase 3 activity and DNA damage. This study shows the promising neuroprotective ability of the two dihydrochalcones able to protect human differentiated neuroblastoma cells (commonly used as model of Parkinson's disease) from injury induced by rotenone, actively scavenging ROS, normalizing mitochondrial transmembrane potential and consequently avoiding energy depletion. © 2017 BioFactors, 43(4):549-557, 2017.
Collapse
Affiliation(s)
- Davide Barreca
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy
| | - Monica Currò
- Department of Biomedical Sciences, Dental Sciences and Morpho-functional Imaging, Polyclinic Hospital University, Via C. Valeria, Messina, Italy
| | - Ersilia Bellocco
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy
| | - Silvana Ficarra
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy
| | - Giuseppina Laganà
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy
| | - Ester Tellone
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy
| | - Maria Laura Giunta
- Department of Biomedical Sciences, Dental Sciences and Morpho-functional Imaging, Polyclinic Hospital University, Via C. Valeria, Messina, Italy
| | - Giuseppa Visalli
- Department of Biomedical Sciences, Dental Sciences and Morpho-functional Imaging, Polyclinic Hospital University, Via C. Valeria, Messina, Italy
| | - Daniela Caccamo
- Department of Biomedical Sciences, Dental Sciences and Morpho-functional Imaging, Polyclinic Hospital University, Via C. Valeria, Messina, Italy
| | - Antonio Galtieri
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy
| | - Riccardo Ientile
- Department of Biomedical Sciences, Dental Sciences and Morpho-functional Imaging, Polyclinic Hospital University, Via C. Valeria, Messina, Italy
| |
Collapse
|
|
33
|
Wang Y, Shen RW, Han B, Li Z, Xiong L, Zhang FY, Cong BB, Zhang B. Notch signaling mediated by TGF-β/Smad pathway in concanavalin A-induced liver fibrosis in rats. World J Gastroenterol 2017; 23:2330-2336. [PMID: 28428712 PMCID: PMC5385399 DOI: 10.3748/wjg.v23.i13.2330] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2016] [Revised: 01/26/2017] [Accepted: 02/17/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To explore the exact interaction between Notch and transforming growth factor (TGF)-β signaling in liver fibrosis.
METHODS We established a rat model of liver fibrosis induced by concanavalin A. Peripheral blood mononuclear cells (PBMCs) were isolated from the modeled rats, and cultured with γ-secretase inhibitor DAPT and TGF-β inhibitor for 24 h. The mRNA levels of Notch and TGF-β signaling were detected by quantitative real-time polymerase chain reaction. Expression of Notch and TGF-β proteins was analyzed by western blotting.
RESULTS Compared to control rats, Notch and TGF-β signaling was activated in PBMCs of model rats. Administration of DAPT and TGF-β inhibitor suppressed Notch and TGF-β signal transducer in PBMCs of model rats. DAPT reduced mRNA and protein expression of TGF-β signaling, such as TGF-β1 and Smad3. TGF-β inhibitor also downregulated Notch1, Hes1 and Hes5, and mRNA and protein expression of the Notch signaling pathway.
CONCLUSION Notch and TGF-β signaling play a role in liver fibrosis. TGF-β signaling upregulates Notch signaling, which promotes TGF-β signaling.
Collapse
|
|
34
|
Mohr Gregoriussen AM, Bohr HG. A Novel Model on DST-Induced Transplantation Tolerance by the Transfer of Self-Specific Donor tTregs to a Haplotype-Matched Organ Recipient. Front Immunol 2017; 8:9. [PMID: 28270810 PMCID: PMC5319400 DOI: 10.3389/fimmu.2017.00009] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2016] [Accepted: 01/04/2017] [Indexed: 12/27/2022] Open
Abstract
Donor-specific blood transfusion (DST) can lead to significant prolongation of allograft survival in experimental animal models and sometimes human recipients of solid organs. The mechanisms responsible for the beneficial effect on graft survival have been a topic of research and debate for decades and are not yet fully elucidated. Once we discover how the details of the mechanisms involved are linked, we could be within reach of a procedure making it possible to establish donor-specific tolerance with minimal or no immunosuppressive medication. Today, it is well established that CD4+Foxp3+ regulatory T cells (Tregs) are indispensable for maintaining immunological self-tolerance. A large number of animal studies have also shown that Tregs are essential for establishing and maintaining transplantation tolerance. In this paper, we present a hypothesis of one H2-haplotype-matched DST-induced transplantation tolerance (in mice). The formulated hypothesis is based on a re-interpretation of data from an immunogenetic experiment published by Niimi and colleagues in 2000. It is of importance that the naïve recipient mice in this study were never immunosuppressed and were therefore fully immune competent during the course of tolerance induction. Based on the immunological status of the recipients, we suggest that one H2-haplotype-matched self-specific Tregs derived from the transfusion blood can be activated and multiply in the host by binding to antigen-presenting cells presenting allopeptides in their major histocompatibility complex (MHC) class II (MHC-II). We also suggest that the endothelial and epithelial cells within the solid organ allograft upregulate the expression of MHC-II and attract the expanded Treg population to suppress inflammation within the graft. We further suggest that this biological process, here termed MHC-II recruitment, is a vital survival mechanism for organs (or the organism in general) when attacked by an immune system.
Collapse
Affiliation(s)
| | - Henrik Georg Bohr
- Department of Chemistry, The Technical University of Denmark , Lyngby , Denmark
| |
Collapse
|
|
35
|
Kazanski V, Mitrokhin VM, Mladenov MI, Kamkin AG. Cytokine Effects on Mechano-Induced Electrical Activity in Atrial Myocardium. Immunol Invest 2016; 46:22-37. [PMID: 27617892 DOI: 10.1080/08820139.2016.1208220] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
The role of cytokines as regulators of stretch-related mechanisms is of special importance since mechano-sensitivity plays an important role in a wide variety of biological processes. Here, we elucidate the influence of cytokine application on mechano-sensitivity and mechano-transduction. The atrial myocardial stretch induces production of interleukin (IL)-2, IL-6, IL-13, IL-17A, and IL-18 with exception of tumor necrosis factor α (TNF-α), IL-1β, and vascular endothelial growth factor B (VEGF-B). Positive ionotropic effect was specific for VEGF-B, negative ionotropic effects were specific for TNF-α, IL-1β, IL-2, IL-6, IL-13, IL-17A and IL-18, while IL-1α doesn't show direct ionotropic effect. The IL-2, IL-6, IL-17A, IL-18, and VEGF-B cause elongation of the APD, in comparison with the reduced APD caused by the IL-13. The TNF-α, IL-1β, and IL-18 influences L-type Ca2+ channels, IL-2 has an inhibitory effect on the fast Na+ channels while IL-17A and VEGF-B were specific for Kir channels. With exception of the IL-1α, IL-2, and VEGF-B, all analyzed cytokines include nitric oxide dependent signaling with resultant combined effects on mechano-gated and Ca2+ channels. The relationships between these pathways and the time-dependence of their activation are of important considerations in the evaluation of cytokine-induced electrical abnormality, specific for cardiac dysfunctions. In general, the discussion presented in this review covers research devoted to counterbalance between different cytokines in the regulation of stretch-induced effects in rat atrial myocardium. ABBREVIATIONS APs: action potentials; APD25: action potential durations to 25% of re-polarization; APD50: action potential durations to 50% of repolarization; APD90: action potential durations to 90% of repolarization; MGCs: mechanically gated channels.
Collapse
Affiliation(s)
- V Kazanski
- a Department of Fundamental and Applied Physiology , Russian National Research Medical University , Moscow , Russia
| | - V M Mitrokhin
- a Department of Fundamental and Applied Physiology , Russian National Research Medical University , Moscow , Russia
| | - M I Mladenov
- a Department of Fundamental and Applied Physiology , Russian National Research Medical University , Moscow , Russia.,b Faculty of Natural Sciences and Mathematics, Institute of Biology , "Ss. Cyril and Methodius" University , Skopje , Macedonia
| | - A G Kamkin
- a Department of Fundamental and Applied Physiology , Russian National Research Medical University , Moscow , Russia
| |
Collapse
|
|
36
|
Vasquez A, Malavera A, Doruk D, Morales-Quezada L, Carvalho S, Leite J, Fregni F. Duration Dependent Effects of Transcranial Pulsed Current Stimulation (tPCS) Indexed by Electroencephalography. Neuromodulation 2016; 19:679-688. [PMID: 27400423 DOI: 10.1111/ner.12457] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2015] [Revised: 04/16/2016] [Accepted: 04/29/2016] [Indexed: 11/28/2022]
Abstract
OBJECTIVE To explore the duration of tPCS after effects given different durations of stimulation on power and interhemispheric coherence of the EEG frequency bands. Our hypothesis was that longer tPCS duration would induce a differential effect on the EEG analysis and a longer duration of after effects on the EEG frequency bands. MATERIALS AND METHODS We conducted a double blind, sham controlled study in which forty healthy subjects were randomized to receive a single session of either 10, 20, 30 min of active (2 mA, random frequency between 6 and 10 Hz, ear clip montage) or sham tPCS. EEG was recorded before and after the intervention to assess tPCS induced after effects. RESULTS We found that 10 and 20 min of active tPCS induced a significant increase in alpha (p = 0.004) and theta (p = 0.006) coherence in the frontal region as compared with the sham stimulation. No significant changes were found with 30 min of stimulation (p < 0.05). The Kaplan Meier analysis showed that 10 and 20 min of tPCS induced after effects that lasted 50 min. CONCLUSIONS These results evidence the nonlinear relationship between the stimulation duration and the tPCS after effects, suggesting the presence of homeostatic mechanisms.
Collapse
Affiliation(s)
- Alejandra Vasquez
- Spaulding Neuromodulation Center, Spaulding Rehabilitation Hospital, Harvard Medical School, Boston, MA, USA
| | - Alejandra Malavera
- Spaulding Neuromodulation Center, Spaulding Rehabilitation Hospital, Harvard Medical School, Boston, MA, USA
| | - Deniz Doruk
- Spaulding Neuromodulation Center, Spaulding Rehabilitation Hospital, Harvard Medical School, Boston, MA, USA
| | - Leon Morales-Quezada
- Spaulding Neuromodulation Center, Spaulding Rehabilitation Hospital, Harvard Medical School, Boston, MA, USA.,Department of Physical Medicine and Rehabilitation, School of Health Sciences, De Montfort University, Leicester, UK.,Division of General Medicine and Primary Care, Beth Israel Deaconess Medical Center, Brookline, MA, USA
| | - Sandra Carvalho
- Spaulding Neuromodulation Center, Spaulding Rehabilitation Hospital, Harvard Medical School, Boston, MA, USA.,Neuropsychophysiology Laboratory, CIPsi, School of Psychology, University of Minho, Campus de Gualtar, Braga, Portugal
| | - Jorge Leite
- Spaulding Neuromodulation Center, Spaulding Rehabilitation Hospital, Harvard Medical School, Boston, MA, USA.,Neuropsychophysiology Laboratory, CIPsi, School of Psychology, University of Minho, Campus de Gualtar, Braga, Portugal
| | - Felipe Fregni
- Spaulding Neuromodulation Center, Spaulding Rehabilitation Hospital, Harvard Medical School, Boston, MA, USA.
| |
Collapse
|
|
37
|
Asalla S, Girada SB, Kuna RS, Chowdhury D, Kandagatla B, Oruganti S, Bhadra U, Bhadra MP, Kalivendi SV, Rao SP, Row A, Ibrahim A, Ghosh PP, Mitra P. Restoring Mitochondrial Function: A Small Molecule-mediated Approach to Enhance Glucose Stimulated Insulin Secretion in Cholesterol Accumulated Pancreatic beta cells. Sci Rep 2016; 6:27513. [PMID: 27282931 PMCID: PMC4901343 DOI: 10.1038/srep27513] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2015] [Accepted: 05/17/2016] [Indexed: 12/20/2022] Open
Abstract
Dyslipidemia, particularly the elevated serum cholesterol levels, aggravate the pathophysiology of type 2 diabetes. In the present study we explored the relationship between fasting blood sugar and serum lipid parameters in human volunteers which revealed a significant linear effect of serum cholesterol on fasting blood glucose. Short term feeding of cholesterol enriched diet to rodent model resulted in elevated serum cholesterol levels, cholesterol accumulation in pancreatic islets and hyperinsulinemia with modest increase in plasma glucose level. To explore the mechanism, we treated cultured BRIN-BD11 pancreatic beta cells with soluble cholesterol. Our data shows that cholesterol treatment of cultured pancreatic beta cells enhances total cellular cholesterol. While one hour cholesterol exposure enhances insulin exocytosis, overnight cholesterol accumulation in cultured pancreatic beta cells affects cellular respiration, and inhibits Glucose stimulated insulin secretion. We further report that (E)-4-Chloro-2-(1-(2-(2,4,6-trichlorophenyl) hydrazono) ethyl) phenol (small molecule M1) prevents the cholesterol mediated blunting of cellular respiration and potentiates Glucose stimulated insulin secretion which was abolished in pancreatic beta cells on cholesterol accumulation.
Collapse
Affiliation(s)
- Suman Asalla
- Dr. Reddy's Institute of Life Sciences, University of Hyderabad Campus, Gachibowli, Hyderabad, Telengana, 500046, India.,Dept. of Biochemistry, School of Life Sciences, University of Hyderabad, Gachibowli, Hyderabad, Telangana, 500046, India
| | - Shravan Babu Girada
- Dr. Reddy's Institute of Life Sciences, University of Hyderabad Campus, Gachibowli, Hyderabad, Telengana, 500046, India
| | - Ramya S Kuna
- Dr. Reddy's Institute of Life Sciences, University of Hyderabad Campus, Gachibowli, Hyderabad, Telengana, 500046, India
| | - Debabrata Chowdhury
- Indian Institute of Chemical Technology, Uppal Road, Tarnaka, Telengana, Hyderabad, 500007, India
| | - Bhaskar Kandagatla
- Dr. Reddy's Institute of Life Sciences, University of Hyderabad Campus, Gachibowli, Hyderabad, Telengana, 500046, India
| | - Srinivas Oruganti
- Dr. Reddy's Institute of Life Sciences, University of Hyderabad Campus, Gachibowli, Hyderabad, Telengana, 500046, India
| | - Utpal Bhadra
- Center of Cellular and Molecular Biology, Habsiguda, Uppal Road, Hyderabad, 500007, India
| | - Manika Pal Bhadra
- Indian Institute of Chemical Technology, Uppal Road, Tarnaka, Telengana, Hyderabad, 500007, India
| | - Shasi Vardhan Kalivendi
- Indian Institute of Chemical Technology, Uppal Road, Tarnaka, Telengana, Hyderabad, 500007, India
| | - Swetha Pavani Rao
- Indian Institute of Chemical Technology, Uppal Road, Tarnaka, Telengana, Hyderabad, 500007, India
| | - Anupama Row
- University of Hyderabad Health Center, University of Hyderabad, Gachibowli, Hyderabad, Telengana, 500046, India
| | - A Ibrahim
- Department of Biochemistry, National Institute of Nutrition, Hyderabad 500007, India
| | - Partha Pratim Ghosh
- Microsoft India (R&D) Pvt. Ltd, Gachibowli, Hyderabad, Telengana, 500032, India
| | - Prasenjit Mitra
- Dr. Reddy's Institute of Life Sciences, University of Hyderabad Campus, Gachibowli, Hyderabad, Telengana, 500046, India
| |
Collapse
|
|
38
|
Martin RM, Herce HD, Ludwig AK, Cardoso MC. Visualization of the Nucleolus in Living Cells with Cell-Penetrating Fluorescent Peptides. Methods Mol Biol 2016; 1455:71-82. [PMID: 27576711 DOI: 10.1007/978-1-4939-3792-9_6] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
The nucleolus is the hallmark of nuclear compartmentalization and has been shown to exert multiple roles in cellular metabolism besides its main function as the place of ribosomal RNA synthesis and assembly of ribosomes. The nucleolus plays also a major role in nuclear organization as the largest compartment within the nucleus. The prominent structure of the nucleolus can be detected using contrast light microscopy providing an approximate localization of the nucleolus, but this approach does not allow to determine accurately the three-dimensional structure of the nucleolus in cells and tissues. Immunofluorescence staining with antibodies specific to nucleolar proteins albeit very useful is time consuming, normally antibodies recognize their epitopes only within a small range of species and is applicable only in fixed cells. Here, we present a simple method to selectively and accurately label this ubiquitous subnuclear compartment in living cells of a large range of species using a fluorescently labeled cell-penetrating peptide.
Collapse
Affiliation(s)
- Robert M Martin
- Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028, Lisbon, Portugal
| | - Henry D Herce
- Department of Biology, Technische Universität Darmstadt, Schnittspahnstr. 10, 64287, Darmstadt, Germany
| | - Anne K Ludwig
- Department of Biology, Technische Universität Darmstadt, Schnittspahnstr. 10, 64287, Darmstadt, Germany
| | - M Cristina Cardoso
- Department of Biology, Technische Universität Darmstadt, Schnittspahnstr. 10, 64287, Darmstadt, Germany.
| |
Collapse
|
|
39
|
Venom peptides as a rich source of cav2.2 channel blockers. Toxins (Basel) 2013; 5:286-314. [PMID: 23381143 PMCID: PMC3640536 DOI: 10.3390/toxins5020286] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2012] [Revised: 01/07/2013] [Accepted: 01/25/2013] [Indexed: 11/24/2022] Open
Abstract
Cav2.2 is a calcium channel subtype localized at nerve terminals, including nociceptive fibers, where it initiates neurotransmitter release. Cav2.2 is an important contributor to synaptic transmission in ascending pain pathways, and is up-regulated in the spinal cord in chronic pain states along with the auxiliary α2δ1 subunit. It is therefore not surprising that toxins that inhibit Cav2.2 are analgesic. Venomous animals, such as cone snails, spiders, snakes, assassin bugs, centipedes and scorpions are rich sources of remarkably potent and selective Cav2.2 inhibitors. However, side effects in humans currently limit their clinical use. Here we review Cav2.2 inhibitors from venoms and their potential as drug leads.
Collapse
|