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Guo H, Xu X, Zhang J, Du Y, Yang X, He Z, Zhao L, Liang T, Guo L. The Pivotal Role of Preclinical Animal Models in Anti-Cancer Drug Discovery and Personalized Cancer Therapy Strategies. Pharmaceuticals (Basel) 2024; 17:1048. [PMID: 39204153 PMCID: PMC11357454 DOI: 10.3390/ph17081048] [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: 07/14/2024] [Revised: 08/02/2024] [Accepted: 08/07/2024] [Indexed: 09/03/2024] Open
Abstract
The establishment and utilization of preclinical animal models constitute a pivotal aspect across all facets of cancer research, indispensably contributing to the comprehension of disease initiation and progression mechanisms, as well as facilitating the development of innovative anti-cancer therapeutic approaches. These models have emerged as crucial bridges between basic and clinical research, offering multifaceted support to clinical investigations. This study initially focuses on the importance and benefits of establishing preclinical animal models, discussing the different types of preclinical animal models and recent advancements in cancer research. It then delves into cancer treatment, studying the characteristics of different stages of tumor development and the development of anti-cancer drugs. By integrating tumor hallmarks and preclinical research, we elaborate on the path of anti-cancer drug development and provide guidance on personalized cancer therapy strategies, including synthetic lethality approaches and novel drugs widely adopted in the field. Ultimately, we summarize a strategic framework for selecting preclinical safety experiments, tailored to experimental modalities and preclinical animal species, and present an outlook on the prospects and challenges associated with preclinical animal models. These models undoubtedly offer new avenues for cancer research, encompassing drug development and personalized anti-cancer protocols. Nevertheless, the road ahead continues to be lengthy and fraught with obstacles. Hence, we encourage researchers to persist in harnessing advanced technologies to refine preclinical animal models, thereby empowering these emerging paradigms to positively impact cancer patient outcomes.
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Affiliation(s)
- Haochuan Guo
- Jiangsu Key Laboratory for Molecular and Medical Biotechnology, School of Life Science, Nanjing Normal University, Nanjing 210023, China; (H.G.); (X.X.); (J.Z.); (Y.D.); (X.Y.)
| | - Xinru Xu
- Jiangsu Key Laboratory for Molecular and Medical Biotechnology, School of Life Science, Nanjing Normal University, Nanjing 210023, China; (H.G.); (X.X.); (J.Z.); (Y.D.); (X.Y.)
| | - Jiaxi Zhang
- Jiangsu Key Laboratory for Molecular and Medical Biotechnology, School of Life Science, Nanjing Normal University, Nanjing 210023, China; (H.G.); (X.X.); (J.Z.); (Y.D.); (X.Y.)
| | - Yajing Du
- Jiangsu Key Laboratory for Molecular and Medical Biotechnology, School of Life Science, Nanjing Normal University, Nanjing 210023, China; (H.G.); (X.X.); (J.Z.); (Y.D.); (X.Y.)
| | - Xinbing Yang
- Jiangsu Key Laboratory for Molecular and Medical Biotechnology, School of Life Science, Nanjing Normal University, Nanjing 210023, China; (H.G.); (X.X.); (J.Z.); (Y.D.); (X.Y.)
| | - Zhiheng He
- State Key Laboratory of Organic Electronics and Information Displays & Institute of Advanced Materials (IAM), Nanjing University of Posts & Telecommunications, 9 Wenyuan Road, Nanjing 210023, China; (Z.H.); (L.Z.)
| | - Linjie Zhao
- State Key Laboratory of Organic Electronics and Information Displays & Institute of Advanced Materials (IAM), Nanjing University of Posts & Telecommunications, 9 Wenyuan Road, Nanjing 210023, China; (Z.H.); (L.Z.)
| | - Tingming Liang
- Jiangsu Key Laboratory for Molecular and Medical Biotechnology, School of Life Science, Nanjing Normal University, Nanjing 210023, China; (H.G.); (X.X.); (J.Z.); (Y.D.); (X.Y.)
| | - Li Guo
- State Key Laboratory of Organic Electronics and Information Displays & Institute of Advanced Materials (IAM), Nanjing University of Posts & Telecommunications, 9 Wenyuan Road, Nanjing 210023, China; (Z.H.); (L.Z.)
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2
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Samaran Q, Dereure O, Raison-Peyron N. Allergic contact dermatitis to zinc ricinoleate in a 'natural' deodorant. Contact Dermatitis 2024; 91:76-78. [PMID: 38553652 DOI: 10.1111/cod.14550] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2023] [Revised: 02/28/2024] [Accepted: 03/13/2024] [Indexed: 06/04/2024]
Affiliation(s)
- Quentin Samaran
- Department of Dermatology, Montpellier University Hospital and Montpellier University, Montpellier, France
| | - Olivier Dereure
- Department of Dermatology, Montpellier University Hospital and Montpellier University, Montpellier, France
| | - Nadia Raison-Peyron
- Department of Dermatology, Montpellier University Hospital and Montpellier University, Montpellier, France
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Nisbett KE, Vendruscolo LF, Koob GF. Indulging Curiosity: Preliminary Evidence of an Anxiolytic-like Effect of Castor Oil and Ricinoleic Acid. Nutrients 2024; 16:1527. [PMID: 38794765 PMCID: PMC11124509 DOI: 10.3390/nu16101527] [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: 04/01/2024] [Revised: 05/09/2024] [Accepted: 05/15/2024] [Indexed: 05/26/2024] Open
Abstract
In the process of validating the elevated zero maze, a common test of anxiety-like behavior, in our laboratory, we demonstrated an anxiolytic-like effect of castor oil and its primary component, ricinoleic acid. We tested the effects of vehicle and chlordiazepoxide in male mice in the elevated zero maze following a 30-min pretreatment time. Chlordiazepoxide is a United States Food and Drug Administration-approved drug that was previously shown to exert anxiolytic-like effects in both the elevated zero maze and elevated plus maze. Chlordiazepoxide was administered at doses of 5 or 10 mg/kg. We used 5% polyoxyl 35 castor oil (Kolliphor® EL) and saline as treatment vehicles and found that the effect of chlordiazepoxide on open zone occupancy and open zone entries was blunted when 5% Kolliphor was used as the vehicle. These tests demonstrated that chlordiazepoxide increased open zone occupancy and entries in the elevated zero maze more effectively when saline was used as the treatment vehicle and that Kolliphor dampened the anxiolytic-like effect of chlordiazepoxide when it was used as the treatment vehicle. Notably, 5% Kolliphor alone slightly increased baseline open zone occupancy and entries. Given that Kolliphor is a derivative of castor oil, we next tested the effect of 5% castor oil and 5% ricinoleic acid, which is a major component of castor oil. We found that both castor oil and ricinoleic acid increased open zone occupancy but not entries compared with saline. Altogether, our findings demonstrate that Kolliphor, castor oil, and ricinoleic acid may exert anxiolytic-like effects in male mice in the elevated zero maze. This potential anxiolytic-like effect of castor oil is consistent with its well-established beneficial effects, including anti-inflammatory, antioxidant, antifungal, and pain-relieving properties.
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Affiliation(s)
- Khalin E. Nisbett
- Graduate Program in Neuroscience, Graduate College, University of Illinois Chicago, Chicago, IL 60607, USA
- Stress and Addiction Neuroscience Unit, Integrative Neuroscience Research Branch, National Institute on Drug Abuse Intramural Research Program and National Institute on Alcohol Abuse and Alcoholism Division of Intramural Clinical and Biological Research, National Institutes of Health, Baltimore, MD 21224, USA
- Neurobiology of Addiction Section, Integrative Neuroscience Research Branch, National Institute on Drug Abuse Intramural Research Program, National Institutes of Health, Baltimore, MD 21224, USA
| | - Leandro F. Vendruscolo
- Stress and Addiction Neuroscience Unit, Integrative Neuroscience Research Branch, National Institute on Drug Abuse Intramural Research Program and National Institute on Alcohol Abuse and Alcoholism Division of Intramural Clinical and Biological Research, National Institutes of Health, Baltimore, MD 21224, USA
| | - George F. Koob
- Neurobiology of Addiction Section, Integrative Neuroscience Research Branch, National Institute on Drug Abuse Intramural Research Program, National Institutes of Health, Baltimore, MD 21224, USA
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Sullivan AG, Murthy R, Roos JCP. Comment on: Epimax-related ocular surface toxicity (EROST): the Glasgow experience. Eye (Lond) 2024; 38:817. [PMID: 37777660 PMCID: PMC10920858 DOI: 10.1038/s41433-023-02778-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2023] [Revised: 09/25/2023] [Accepted: 09/25/2023] [Indexed: 10/02/2023] Open
Affiliation(s)
| | - Rachna Murthy
- FaceRestoration, 25 Harley Street, London, W1G 9QW, UK
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Jiménez-González V, Kowalczyk T, Piekarski J, Szemraj J, Rijo P, Sitarek P. Nature's Green Potential: Anticancer Properties of Plants of the Euphorbiaceae Family. Cancers (Basel) 2023; 16:114. [PMID: 38201542 PMCID: PMC10778523 DOI: 10.3390/cancers16010114] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2023] [Revised: 12/17/2023] [Accepted: 12/21/2023] [Indexed: 01/12/2024] Open
Abstract
The number of cancer cases will reach 24 million in 2040, according to the International Agency for Research on Cancer. Current treatments for cancer are not effective and selective for most patients; for this reason, new anticancer drugs need to be developed and researched enough. There are potentially useful drugs for cancer isolated from plants that are being used in the clinic. Available information about phytochemistry, traditional uses, in vitro and in vivo experiments with plants, and pure compounds isolated from the Euphorbiaceae family indicates that this family of plants has the potential to develop anticancer drugs. This review examines selected species from the Euphorbiaceae family and their bioactive compounds that could have potential against different types of cancer cells. It reviews the activity of crude extracts, isolated compounds, and nanoparticles and the potential underlying mechanisms of action.
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Affiliation(s)
- Víctor Jiménez-González
- Department of Pharmacology, Faculty of Pharmacy, University of Seville, 41012 Seville, Spain
| | - Tomasz Kowalczyk
- Department of Molecular Biotechnology and Genetics, Faculty of Biology and Environmental Protection, University of Lodz, Banacha 12/16, 90-237 Lodz, Poland
| | - Janusz Piekarski
- Department of Surgical Oncology, Medical University in Lodz, 93-513 Lodz, Poland;
| | - Janusz Szemraj
- Department of Medical Biochemistry, Medical University of Lodz, 92-215 Lodz, Poland;
| | - Patricia Rijo
- CBIOS-Lusófona University’s Research Center for Biosciences and Health Technologies, 1749-024 Lisbon, Portugal;
- Instituto de Investigação do Medicamento (iMed.ULisboa), Faculdade de Farmácia, Universidade de Lisboa, 1649-003 Lisbon, Portugal
| | - Przemysław Sitarek
- Department of Medical Biology, Medical University of Lodz, 90-151 Lodz, Poland;
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Senthilnathan S, Jayaraman S, Priya Veeraraghavan V, Masood Khan J, Ahmed MZ, Ahmad A, Gnanamani A. HPTLC and GC-MS finger-printing of two potential multifunctional siddha tailams: Mathan and maha megarajanga tailam. Saudi J Biol Sci 2023; 30:103700. [PMID: 37333677 PMCID: PMC10276281 DOI: 10.1016/j.sjbs.2023.103700] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2023] [Revised: 05/16/2023] [Accepted: 05/24/2023] [Indexed: 06/20/2023] Open
Abstract
The Siddha system of medicine is an ancient medical lineage that is practiced primarily in the southern part of India. Siddha system of medicine has been in practice for thousands of years with documented evidence dating back to the 6th century BCE. According to siddha system of medicine's basic fundamental principle, the human body is made up of 96 thathuvam (primary components), which encompass physical, physiological, psychological, and intellectual aspects. Medicine (marunthu) is classified as a wide range of internal and external medicines. The major components of its medical formulations include plant parts, minerals and animal products. Various methods were carried out for the purification process to eliminate the toxins. Choornam, Guligai, Tailam, Parpam, Chendooram, Kattu, Pasai and Poochu are the most common medicines used in Siddha system of medicine for the treatment of various diseases. The pathophysiological classification of diseases is elaborated in detail in the classical Siddha literature. Siddha system of medicine plays an important role in protecting people from diseases such as COVID-19 by providing immune-protecting and immune-boosting medicines in today's world. Mathan tailam and maha megarajanga tailam are the two unique preparations used widely for various skin diseases including chronic wounds and burns. Scientific validation of both medicines will help in understanding their effectiveness against a typical wound condition. In the present study physio-chemical and phytochemical, HPTLC, and GC-MS analyses were carried out and discussed in detail on the multifunctional properties exhibited in the patient communities.
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Affiliation(s)
| | - Selvaraj Jayaraman
- Centre of Molecular Medicine and Diagnostics (COMManD), Department of Biochemistry, Saveetha Dental College & Hospitals, Saveetha Institute of Medical & Technical Sciences, Saveetha University, Chennai 600077, India
| | - Vishnu Priya Veeraraghavan
- Centre of Molecular Medicine and Diagnostics (COMManD), Department of Biochemistry, Saveetha Dental College & Hospitals, Saveetha Institute of Medical & Technical Sciences, Saveetha University, Chennai 600077, India
| | - Javed Masood Khan
- Department of Food Science and Nutrition, Faculty of Food and Agricultural Sciences, King Saud University, 2460, Riyadh 11451, Saudi Arabia
| | - Mohammad Z. Ahmed
- Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
| | - Anis Ahmad
- Department of Radiation Oncology, Miller School of Medicine/Sylvester Cancer Center, University of Miami, Miami, FL, USA
| | - Arumugam Gnanamani
- Microbiology Laboratory, CSIR- Central Leather Research Institute, Adyar, Chennai 600020, India
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Fiume MM, Bergfeld WF, Belsito DV, Hill RA, Klaassen CD, Liebler DC, Marks JG, Shank RC, Slaga TJ, Snyder PW, Gill LJ, Heldreth B. Safety Assessment of Polyglyceryl Fatty Acid Esters as Used in Cosmetics. Int J Toxicol 2023:10915818231174440. [PMID: 37279183 DOI: 10.1177/10915818231174440] [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: 06/08/2023]
Abstract
The Expert Panel for Cosmetic Ingredient Safety (Panel) assessed the safety of 274 polyglyceryl fatty acid esters. Each of the esters in this group is a polyether comprising 2 to 20 glyceryl residues, end-capped by esterification with simple carboxylic acids, such as fatty acids. Most of these ingredients are reported to function in cosmetics as skin-conditioning agents and/or surfactants. The Panel reviewed the available data and considered conclusions from their relevant previous reports, and determined that these ingredients are safe in cosmetics in the present practices of use and concentration described in this safety assessment when formulated to be non-irritating.
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Affiliation(s)
- Monice M Fiume
- Cosmetic Ingredient Review Senior Director, Washington, DC, USA
| | - Wilma F Bergfeld
- Expert Panel for Cosmetic Ingredient Safety Member, Washington, DC, USA
| | - Donald V Belsito
- Expert Panel for Cosmetic Ingredient Safety Member, Washington, DC, USA
| | - Ronald A Hill
- Expert Panel for Cosmetic Ingredient Safety Former Member, Washington, DC, USA
| | - Curtis D Klaassen
- Expert Panel for Cosmetic Ingredient Safety Member, Washington, DC, USA
| | - Daniel C Liebler
- Expert Panel for Cosmetic Ingredient Safety Former Member, Washington, DC, USA
| | - James G Marks
- Expert Panel for Cosmetic Ingredient Safety Former Member, Washington, DC, USA
| | - Ronald C Shank
- Expert Panel for Cosmetic Ingredient Safety Former Member, Washington, DC, USA
| | - Thomas J Slaga
- Expert Panel for Cosmetic Ingredient Safety Member, Washington, DC, USA
| | - Paul W Snyder
- Expert Panel for Cosmetic Ingredient Safety Member, Washington, DC, USA
| | - Lillian J Gill
- Cosmetic Ingredient Review Former Director, Washington, DC, USA
| | - Bart Heldreth
- Cosmetic Ingredient Review Executive Director, Washington, DC, USA
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Thuy LT, Lee S, Dongquoc V, Choi JS. Nanoemulsion Composed of α-Tocopherol Succinate and Dequalinium Shows Mitochondria-Targeting and Anticancer Effects. Antioxidants (Basel) 2023; 12:antiox12020437. [PMID: 36829996 PMCID: PMC9952168 DOI: 10.3390/antiox12020437] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2023] [Revised: 02/06/2023] [Accepted: 02/08/2023] [Indexed: 02/12/2023] Open
Abstract
Targeted drugs have been used to treat mitochondrial dysfunction-related diseases, including metabolic disorders and cancer; however, targeting and penetrating intracellular organelles remains a challenge. Dominant targeting approaches for therapeutic delivery are detailed in many nanoemulsion studies and show the tremendous potential of targeted delivery to inhibit cancer cell growth. Dequalinium (DQA) and α-tocopherol succinate (α-TOS) are good agents for targeting mitochondria. In this study, we aimed to develop a mitochondria-targeting emulsion, using DQA and α-TOS (DTOS), for cancer treatment. DTOS emulsions of 150-170 nm in diameter were formulated using homogenization. DQA and α-TOS were used as bifunctional agents (surfactants) to stabilize the nanoemulsion and anticancer drugs. Various molar ratios of DQA and α-TOS were tested to determine the optimal condition, and DTOS 5-5 was selected for further study. The DTOS emulsion showed improved stability, as evidenced by its ability to remain stable for three years at room temperature. This stability, combined with its effective targeting of mitochondria, led to inhibition of 71.5% of HeLa cells after 24 h. The DTOS emulsion effectively inhibited spheroid growth in the 3D model, as well as prevented the growth of HeLa cells grafted onto zebrafish larvae. These results highlight the DTOS emulsion's promising potential for mitochondria-targeting and cancer treatment.
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Affiliation(s)
- Le Thi Thuy
- Department of Biochemistry, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 34134, Republic of Korea
| | - Seulgi Lee
- KM Science Research Division, Korea Institute of Oriental Medicine, Yuseong-daero 1672, Yuseong-gu, Daejeon 34054, Republic of Korea
| | - Viet Dongquoc
- Department of Materials Science and Engineering, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 34134, Republic of Korea
| | - Joon Sig Choi
- Department of Biochemistry, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 34134, Republic of Korea
- Correspondence: ; Tel.: +82-42-821-7528; Fax: +82-42-822-7548
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Schripsema J, da Silva SM, Dagnino D. Differential NMR and chromatography for the detection and analysis of adulteration of vetiver essential oils. Talanta 2022; 237:122928. [PMID: 34736665 DOI: 10.1016/j.talanta.2021.122928] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2021] [Revised: 09/29/2021] [Accepted: 10/02/2021] [Indexed: 10/20/2022]
Abstract
Adulteration of essential oils is a common and serious problem. Adequate and fast methods are required to establish the authenticity and purity. GC-MS, 1H and 13C NMR were compared in combination with similarity calculations as well as differential spectroscopy and chromatography for the authentication and determination of purity of vetiver essential oils. In the investigation of eight commercial oils 1H and 13C NMR adequately detected all six adulterants encountered in four of the commercial samples, while GC-MS was not able to detect adulteration with vegetable oils. A great advantage of the combined use of similarity calculation and NMR is that the authenticity can be verified without the need of concomitant measurement of a standard sample. The calculation can be carried out with a registered reference spectrum, in the case of 1H NMR acquired using the same magnetic field, but in the case of 13C NMR the spectrum can be obtained with another magnetic field. 1H NMR has the advantage of high speed, and the results can be obtained within minutes. 13C NMR was found to be superior in its ability to provide unequivocal identification of eventual adulterants, with differential spectroscopy revealing all signals of the adulterants.
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Affiliation(s)
- Jan Schripsema
- Grupo Metabolômica, Universidade Estadual do Norte Fluminense, Laboratório de Ciências Quimicas, Av. Alberto Lamego, 2000, 28013-602, Campos dos Goytacazes, RJ, Brazil.
| | - Sônia Maria da Silva
- Grupo Metabolômica, Universidade Estadual do Norte Fluminense, Laboratório de Ciências Quimicas, Av. Alberto Lamego, 2000, 28013-602, Campos dos Goytacazes, RJ, Brazil
| | - Denise Dagnino
- Grupo Metabolômica, Universidade Estadual do Norte Fluminense, Laboratório de Ciências Quimicas, Av. Alberto Lamego, 2000, 28013-602, Campos dos Goytacazes, RJ, Brazil
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American College of Nurse-Midwives, Carlson NS, Amore AD, Ellis JA, Page K, Schafer R. American College of Nurse-Midwives Clinical Bulletin Number 18: Induction of Labor. J Midwifery Womens Health 2022; 67:140-149. [PMID: 35119782 PMCID: PMC9026716 DOI: 10.1111/jmwh.13337] [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: 12/20/2021] [Accepted: 12/20/2021] [Indexed: 11/27/2022]
Abstract
Induction of labor is an increasingly common component of intrapartum care in the United States. This rise is fueled by a nationwide escalation in both medically indicated and elective inductions at or beyond term, supported by recent research showing some benefits of induction over expectant management. However, induction of labor medicalizes the birth experience and may lead to a complex cascade of interventions. The purpose of this Clinical Bulletin is twofold: (1) to guide clinicians on the use of person-centered decision-making when discussing induction of labor and (2) to review evidence-based practice recommendations for intrapartum midwifery care during labor induction.
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Affiliation(s)
| | | | | | | | - Katie Page
- President, RMWC Alumnae and Randolph College Alumni Association; President, VA Affiliate of ACNM
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Novak H, Doering J, Ehrbar D, Donini O, Mantis NJ. Durable Immunity to Ricin Toxin Elicited by a Thermostable, Lyophilized Subunit Vaccine. mSphere 2021; 6:e0075021. [PMID: 34730377 PMCID: PMC8565519 DOI: 10.1128/msphere.00750-21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2021] [Accepted: 10/15/2021] [Indexed: 11/26/2022] Open
Abstract
The development of vaccines against biothreat toxins like ricin (RT) is considered an integral component of the U.S. national security efforts. RiVax is a thermostable, lyophilized RT subunit vaccine adsorbed to aluminum salt adjuvant intended for use by military personnel and first responders. Phase 1 studies indicated that RiVax is safe and immunogenic, while a three-dose intramuscular vaccination regimen in nonhuman primates elicited protection against lethal dose RT challenge by aerosol. Here, we investigated, in a mouse model, the durability of RiVax-induced antibody responses and corresponding immunity to lethal dose RT challenge. Groups of mice were subcutaneously administered 3 or 1 μg of RiVax on days 0 and 21 and challenged with 10× 50% lethal dose (LD50) RT by injection at six different intervals over the course of 12 months. Serum antibody titers and epitope-specific competition assays were determined prior to each challenge. We report that the two-dose, 3-μg regimen conferred near-complete protection against RT challenge on day 35 and complete protection thereafter (challenge days 65, 95, 125, 245, and 365). The two-dose, 3-μg regimen was superior to the 1-μg regimen as revealed by slight differences in survival and morbidity scores (e.g., hypoglycemia, weight loss) on challenge days 35 and 365. In separate experiments, a single 3-μg RiVax vaccination proved only marginally effective at eliciting protective immunity to RT, underscoring the necessity of a prime-boost regimen to achieve full and long-lasting protection against RT. IMPORTANCE Ricin toxin (RT) is a notorious biothreat, as exposure to even trace amounts via injection or inhalation can induce organ failure and death within a matter of hours. In this study, we advance the preclinical testing of a candidate RT vaccine known as RiVax. RiVax is a recombinant nontoxic derivative of RT's enzymatic subunit that has been evaluated for safety in phase I clinical trials and efficacy in a variety of animal models. We demonstrate that two doses of RiVax are sufficient to protect mice from lethal dose RT challenge for up to 1 year. We describe kinetics and other immune parameters of the antibody response to RiVax and discuss how these immune factors may translate to humans.
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Affiliation(s)
- Hayley Novak
- Department of Biomedical Sciences, University at Albany, Albany, New York, USA
| | - Jennifer Doering
- Division of Infectious Disease, Wadsworth Center, New York State Department of Health, Albany, New York, USA
| | - Dylan Ehrbar
- Division of Infectious Disease, Wadsworth Center, New York State Department of Health, Albany, New York, USA
| | | | - Nicholas J. Mantis
- Department of Biomedical Sciences, University at Albany, Albany, New York, USA
- Division of Infectious Disease, Wadsworth Center, New York State Department of Health, Albany, New York, USA
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Narkhede RG, Athawale RB. Screening of Selective C16 to C18 Lipids and Process Optimization Based on Design of Experiments in Formulating Solid Lipid Microparticles by Twin Screw Hot Melt Dispersion Process. J Pharm Innov 2021. [DOI: 10.1007/s12247-021-09575-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
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13
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Shared Makeup Cosmetics as a Route of Demodex folliculorum Infections. Acta Parasitol 2021; 66:631-637. [PMID: 33462683 PMCID: PMC8166727 DOI: 10.1007/s11686-020-00332-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2020] [Accepted: 12/19/2020] [Indexed: 11/08/2022]
Abstract
Purpose The aim of the study was to examine Demodex survival in makeup cosmetics, i.e., powder cream, mascara, and lipstick, and to determine whether cosmetics shared with others can be a source of D. folliculorum infection. Methods Live D. folliculorum adults were placed in cosmetic samples and their motility was observed under a microscope. The mites were fully or partially immersed in the powder cream and lipstick, and only partially immersed in the mascara. Partial immersion means that only the opisthosoma was covered by the cosmetic, whereas the gnathosoma and podosoma had no contact with the cosmetic. Cessation of motility was regarded as a sign of death. Results In the control (mites placed on a microscope slide with no cosmetics), the survival time was 41.2 h. D. folliculorum that were immersed fully or partially in the lipstick substrate were viable for 38.5 h and 148 h, respectively. The survival time of the mites at full and partial immersion in the powder cream was 0.78 h and 2.16 h, respectively. The average survival time in the mascara was 21 h. Conclusions Makeup cosmetics used by different individuals at short intervals (from several hours to several days) can be a source of transmission of Demodex sp. mites. Supplementary Information The online version contains supplementary material available at 10.1007/s11686-020-00332-w.
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Gao C, Gang H, Liu J, Mu B, Yang S. A New Benzylated Fatty Acid Amide Amphoteric Surfactant Derived from Hydrogenated Castor Oil with
Ultra‐Low
Interfacial Tension between Crude Oil and Brine. J SURFACTANTS DETERG 2021. [DOI: 10.1002/jsde.12483] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Affiliation(s)
- Cheng‐Long Gao
- State Key Laboratory of Bioreactor Engineering and Institute of Applied Chemistry East China University of Science and Technology Shanghai 200237 P.R. China
- Engineering Research Center for Microbial Enhanced Energy Recovery Shanghai 200237 P.R. China
| | - Hong‐Ze Gang
- State Key Laboratory of Bioreactor Engineering and Institute of Applied Chemistry East China University of Science and Technology Shanghai 200237 P.R. China
- Engineering Research Center for Microbial Enhanced Energy Recovery Shanghai 200237 P.R. China
| | - Jin‐Feng Liu
- State Key Laboratory of Bioreactor Engineering and Institute of Applied Chemistry East China University of Science and Technology Shanghai 200237 P.R. China
- Engineering Research Center for Microbial Enhanced Energy Recovery Shanghai 200237 P.R. China
| | - Bo‐Zhong Mu
- State Key Laboratory of Bioreactor Engineering and Institute of Applied Chemistry East China University of Science and Technology Shanghai 200237 P.R. China
- Engineering Research Center for Microbial Enhanced Energy Recovery Shanghai 200237 P.R. China
| | - Shi‐Zhong Yang
- State Key Laboratory of Bioreactor Engineering and Institute of Applied Chemistry East China University of Science and Technology Shanghai 200237 P.R. China
- Engineering Research Center for Microbial Enhanced Energy Recovery Shanghai 200237 P.R. China
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15
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Mahmood KA, Rashid RJ, Fateh SM, Mohammed NA. Evaluation of the Effect of Patient Preparation Using Castor Oil on ADC Value of Focal Liver Lesion. Int J Gen Med 2021; 14:469-474. [PMID: 33623419 PMCID: PMC7896795 DOI: 10.2147/ijgm.s289661] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2020] [Accepted: 01/22/2021] [Indexed: 11/23/2022] Open
Abstract
Purpose To estimate the role of patient preparation using castor oil on the ADC value of focal liver lesion. Patients and Methods Retrospective case-control study over more than two years. Magnetic resonance imaging (MRI) scan, including diffusion-weighted imaging (DWI) of the upper abdomen performed for 87 cases and 71 controls in patients with focal hepatic hemangiomas. Cases were prepared using castor oil prior to the scan without identifiable unwanted effect, while controls did not receive any special preparation. Since liver hemangioma is a common lesion, it was selected and used as a sample. Apparent Diffusion Coefficient (ADC) values of focal liver lesion were calculated in cases and controls. Results The mean ADC value of liver hemangioma was lower in cases compared to controls; the mean ADC value was (2.21±0.39x10ˉ3mm2/s) in cases and (2.51±0.49x10ˉ3mm2/s) in controls. Left lobes were more affected by lesions; the mean ADC value of the left lobe lesions was (2.26±0.37 x10ˉ3mm2/s) and (2.86±0.43 x10ˉ3mm2/s) in cases and controls, respectively. The ADC value of lesions in the right lobe was (2.19±0.39x10ˉ3mm2/s) in cases and (2.39± 0.45x10ˉ3mm2/s) in controls. There was a significant segmental ADC variation; lesions at segments II, III, IVb, and V demonstrated illusive ADC elevation in controls. Conclusion There is erroneous elevation of lobar and segmental ADC value of liver hemangiomas in non prepared patients. This Potential source of error (peristalsis, partial volume, and paramagnetic gas effect of gastrointestinal tract) on hepatic lesions’ ADC value can be avoided by proper preparation using castor oil prior to MRI scanning.
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Affiliation(s)
- Kawa Abdulla Mahmood
- University of Sulaimani, College of Medicine, Department of Surgery-Diagnostic Imaging Unit, Sulaymaniyah, Kurdistan Region, Iraq
| | - Rezheen Jamal Rashid
- University of Sulaimani, College of Medicine, Department of Surgery-Diagnostic Imaging Unit, Sulaymaniyah, Kurdistan Region, Iraq
| | - Salah Mohammed Fateh
- University of Sulaimani, College of Medicine, Department of Surgery-Diagnostic Imaging Unit, Sulaymaniyah, Kurdistan Region, Iraq
| | - Naser Abdullah Mohammed
- University of Sulaimani, College of Medicine, Department of Surgery-Diagnostic Imaging Unit, Sulaymaniyah, Kurdistan Region, Iraq
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16
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Thamizhanban A, Balaji S, Lalitha K, Prasad YS, Prasad RV, Kumar RA, Maheswari CU, Sridharan V, Nagarajan S. Glycolipid-Based Oleogels and Organogels: Promising Nanostructured Structuring Agents. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2020; 68:14896-14906. [PMID: 33284625 DOI: 10.1021/acs.jafc.0c02936] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/12/2023]
Abstract
Over the past few decades, the scientific community is actively involved in the development of edible structuring agents suitable for food, cosmetics, agricultural, pharmaceutical, and biotechnology applications. In particular, edible oil structuring using simple amphiphiles would be the best alternative for the currently used trans and saturated fatty acids, which cause deleterious health effects and cardiovascular problems. In this report, we have made an attempt to address the aforementioned consequences, by synthesizing a new class of structuring agents by a judicious combination of δ-gluconolactone and ricinoleic acid, compounds classified as GRAS, using simple steps in good yield. To our delight, the synthesized glycolipids self-assemble in a wide variety of vegetable oils and commercially viable glycerol, ethylene glycol, and polyethylene glycol via various intermolecular interactions to form a gel. The morphology of molecular gels was investigated by optical microscopy and FESEM analysis, which reveal the existence of a tubular architecture with a diameter ranging from 75 to 150 nm. Rheological studies disclosed the viscoelastic nature, thermal processability, and thixotropic behavior of both oleogels and organogels. Altogether, self-assembled oleogel and organogel reported in this paper would potentially be used in food, agricultural, cosmetics, pharmaceutical, and biotechnological applications.
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Affiliation(s)
- Ayyapillai Thamizhanban
- Department of Chemistry, School of Chemical and Biotechnology, SASTRA Deemed University, Thanjavur 613401, Tamil Nadu, India
| | - Srikanth Balaji
- Department of Chemistry, School of Chemical and Biotechnology, SASTRA Deemed University, Thanjavur 613401, Tamil Nadu, India
| | - Krishnamoorthy Lalitha
- Department of Chemistry, School of Chemical and Biotechnology, SASTRA Deemed University, Thanjavur 613401, Tamil Nadu, India
| | - Yadavali Siva Prasad
- Department of Chemistry, School of Chemical and Biotechnology, SASTRA Deemed University, Thanjavur 613401, Tamil Nadu, India
| | - R Vara Prasad
- Department of Chemistry, National Institute of Technology Warangal, Warangal 506004, Telangana, India
| | - R Arun Kumar
- Department of Chemistry, National Institute of Technology Warangal, Warangal 506004, Telangana, India
| | - C Uma Maheswari
- Department of Chemistry, School of Chemical and Biotechnology, SASTRA Deemed University, Thanjavur 613401, Tamil Nadu, India
| | - Vellaisamy Sridharan
- Department of Chemistry and Chemical Sciences, Central University of Jammu, Rahya-Suchani (Bagla), District-Samba, Jammu 181143, India
| | - Subbiah Nagarajan
- Department of Chemistry, School of Chemical and Biotechnology, SASTRA Deemed University, Thanjavur 613401, Tamil Nadu, India
- Department of Chemistry, National Institute of Technology Warangal, Warangal 506004, Telangana, India
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17
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Geck MS, Cristians S, Berger-González M, Casu L, Heinrich M, Leonti M. Traditional Herbal Medicine in Mesoamerica: Toward Its Evidence Base for Improving Universal Health Coverage. Front Pharmacol 2020; 11:1160. [PMID: 32848768 PMCID: PMC7411306 DOI: 10.3389/fphar.2020.01160] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2020] [Accepted: 07/16/2020] [Indexed: 01/28/2023] Open
Abstract
The quality of health care in Mesoamerica is influenced by its rich cultural diversity and characterized by social inequalities. Especially indigenous and rural communities confront diverse barriers to accessing formal health services, leading to often conflicting plurimedical systems. Fostering integrative medicine is a fundamental pillar for achieving universal health coverage (UHC) for marginalized populations. Recent developments toward health sovereignty in the region are concerned with assessing the role of traditional medicines, and particularly herbal medicines, to foster accessible and culturally pertinent healthcare provision models. In Mesoamerica, as in most regions of the world, a wealth of information on traditional and complementary medicine has been recorded. Yet these data are often scattered, making it difficult for policy makers to regulate and integrate traditionally used botanical products into primary health care. This critical review is based on a quantitative analysis of 28 survey papers focusing on the traditional use of botanical drugs in Mesoamerica used for the compilation of the "Mesoamerican Medicinal Plant Database" (MAMPDB), which includes a total of 12,537 use-records for 2188 plant taxa. Our approach presents a fundamental step toward UHC by presenting a pharmacological and toxicological review of the cross-culturally salient plant taxa and associated botanical drugs used in traditional medicine in Mesoamerica. Especially for native herbal drugs, data about safety and effectiveness are limited. Commonly used cross-culturally salient botanical drugs, which are considered safe but for which data on effectiveness is lacking constitute ideal candidates for treatment outcome studies.
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Affiliation(s)
- Matthias S. Geck
- Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy
- Biovision – Foundation for Ecological Development, Zurich, Switzerland
| | - Sol Cristians
- Botanical Garden, Institute of Biology, Universidad Nacional Autónoma de México, Mexico City, Mexico
| | - Mónica Berger-González
- Centro de Estudios en Salud, Universidad del Valle de Guatemala, Guatemala, Guatemala
- Department of Epidemiology and Public Heath, Swiss TPH, University of Basel, Basel, Switzerland
| | - Laura Casu
- Department of Life and Environmental Sciences, University of Cagliari, Cagliari, Italy
| | - Michael Heinrich
- Pharmacognosy and Phytotherapy, UCL School of Pharmacy, London, United Kingdom
| | - Marco Leonti
- Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy
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18
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Londhe VY, Khogta SM, Barve KH. Improved anti-arthritic activity of ginger extract, a traditional medicine, using novel drug delivery approach. JOURNAL OF COMPLEMENTARY & INTEGRATIVE MEDICINE 2020; 18:439-443. [PMID: 32427126 DOI: 10.1515/jcim-2019-0340] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/15/2020] [Accepted: 04/06/2020] [Indexed: 12/17/2023]
Abstract
BACKGROUND Ginger and castor oil, both are used in traditional medicine to treat arthritis, the latter is also commonly used as a vehicle in these systems of medicine. The study was designed to prepare a nanostructured lipid carrier (NLC) of ginger extract using castor oil as a novel liquid lipid and evaluate its safety and efficacy in rheumatoid arthritis in experimental animals. METHODS Ginger extract was standardized using High performance liquid chromatography (HPLC). The optimized NLC formulation was characterized and its therapeutic efficacy was evaluated in Chronic Freund's adjuvant (CFA) induced arthritis in experimental animals. RESULTS Ginger extract contained 38.76 ± 3.01%w/w of 6-gingerol. The optimized NLC formulation showed a particle size of around 205 nm, a zeta potential of -33.7 and %entrapment efficiency of 76.59 ± 0.83%. Reduction in primary inflammation was significantly higher with NLC when compared with ginger extract and castor oil alone (p<0.001). The formulation also improved hyperalgesia in rats. CONCLUSION Castor oil can be used as a novel lipid in the preparation of NLC. The NLC effectively enhanced the therapeutic value of poorly bioavailable ginger extract.
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Affiliation(s)
- Vaishali Y Londhe
- SPP - School of Pharmacy and Technology Management, SVKM's NMIMS, V.L. Mehta Road, Vile Parle (W), Mumbai, Maharashtra, India
| | - Saloni M Khogta
- SPP - School of Pharmacy and Technology Management, SVKM's NMIMS, V.L. Mehta Road, Vile Parle (W), Mumbai, Maharashtra, India
| | - Kalyani H Barve
- SPP - School of Pharmacy and Technology Management, SVKM's NMIMS, V.L. Mehta Road, Vile Parle (W), Mumbai, Maharashtra, 400056, India
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19
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Occurrence and Concentration of Chemical Additives in Consumer Products in Korea. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2019; 16:ijerph16245075. [PMID: 31842379 PMCID: PMC6950561 DOI: 10.3390/ijerph16245075] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/15/2019] [Revised: 12/05/2019] [Accepted: 12/09/2019] [Indexed: 12/25/2022]
Abstract
As the variety of chemicals used in consumer products (CPs) has increased, concerns about human health risk have grown accordingly. Even though restrictive guidelines and regulations have taken place to minimize the risks, human exposure to these chemicals and their eco-compatibility has remained a matter of greater scientific concern over the years. A major challenge in understanding the reality of the exposure is the lack of available information on the increasing number of ingredients and additives in the products. Even when ingredients of CPs formulations are identified on the product containers, the concentrations of the chemicals are rarely known to consumers. In the present study, an integrated target/suspect/non-target screening procedure using liquid chromatography-high resolution mass spectrometry (LC-HRMS) with stepwise identification workflow was used for the identification of known, suspect, and unknown chemicals in CPs including cosmetics, personal care products, and washing agents. The target screening was applied to identify and quantify isothiazolinones and phthalates. Among analyzed CPs, isothiazolinones and phthalates were found in 47% and in 24% of the samples, respectively. The highest concentrations were 518 mg/kg for benzisothiazolone, 7.1 mg/kg for methylisothiazolinone, 2.0 mg/kg for diethyl phthalate, and 21 mg/kg for dimethyl phthalate. Suspect and non-target analyses yielded six tentatively identified chemicals across the products including benzophenone, ricinine, iodocarb (IPBC), galaxolidone, triethanolamine, and 2-(2H-Benzotriazol-2-yl)-4, 6-bis (1-methyl-1-phenylethyl) phenol. Our results revealed that selected CPs consistently contain chemicals from multiple classes. Excessive use of these chemicals in daily life can increase the risk for human health and the environment.
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20
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Chauhan MK, Sharma PK. Optimization and characterization of rivastigmine nanolipid carrier loaded transdermal patches for the treatment of dementia. Chem Phys Lipids 2019; 224:104794. [DOI: 10.1016/j.chemphyslip.2019.104794] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2018] [Revised: 05/02/2019] [Accepted: 07/25/2019] [Indexed: 10/26/2022]
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21
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Maciejewska M, Sowińska A, Kucharska J. Organic Zinc Salts as Pro-Ecological Activators for Sulfur Vulcanization of Styrene-Butadiene Rubber. Polymers (Basel) 2019; 11:polym11101723. [PMID: 31640189 PMCID: PMC6836100 DOI: 10.3390/polym11101723] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2019] [Revised: 10/18/2019] [Accepted: 10/19/2019] [Indexed: 01/19/2023] Open
Abstract
Organic zinc salts and complexes were applied as activators for sulfur vulcanization of styrene–butadiene elastomer (SBR) in order to reduce the content of zinc ions in rubber compounds as compared with conventionally used zinc oxide. In this article, the effects of different organic zinc activators on the curing characteristics, crosslink densities, and mechanical properties of SBR as well as the aging resistance and thermal behavior of vulcanizates are discussed. Organic zinc salts seem to be good substitutes for zinc oxide as activators for sulfur vulcanization of SBR rubber, without detrimental effects to the vulcanization time and temperature. Moreover, vulcanizates containing organic zinc salts exhibit higher tensile strength and better damping properties than vulcanizate crosslinked with zinc oxide. The application of organic zinc activators allows the amount of zinc ions in SBR compounds to be reduced by 70–90 wt % compared to vulcanizate with zinc oxide. This is very important for ecological reasons, since zinc oxide is classified as being toxic to aquatic species.
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Affiliation(s)
- Magdalena Maciejewska
- Institute of Polymer and Dye Technology, Lodz University of Technology, Stefanowskiego Street 12/16, 90-924 Lodz, Poland.
| | - Anna Sowińska
- Institute of Polymer and Dye Technology, Lodz University of Technology, Stefanowskiego Street 12/16, 90-924 Lodz, Poland.
| | - Judyta Kucharska
- Institute of Polymer and Dye Technology, Lodz University of Technology, Stefanowskiego Street 12/16, 90-924 Lodz, Poland.
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22
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Franke H, Scholl R, Aigner A. Ricin and Ricinus communis in pharmacology and toxicology-from ancient use and "Papyrus Ebers" to modern perspectives and "poisonous plant of the year 2018". NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2019; 392:1181-1208. [PMID: 31359089 DOI: 10.1007/s00210-019-01691-6] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/18/2019] [Accepted: 07/04/2019] [Indexed: 12/19/2022]
Abstract
While probably originating from Africa, the plant Ricinus communis is found nowadays around the world, grown for industrial use as a source of castor oil production, wildly sprouting in many regions, or used as ornamental plant. As regards its pharmacological utility, a variety of medical purposes of selected parts of the plant, e.g., as a laxative, an anti-infective, or an anti-inflammatory drug, have been described already in the sixteenth century BC in the famous Papyrus Ebers (treasured in the Library of the University of Leipzig). Quite in contrast, on the toxicological side, the native plant has become the "poisonous plant 2018" in Germany. As of today, a number of isolated components of the plant/seeds have been characterized, including, e.g., castor oil, ricin, Ricinus communis agglutinin, ricinin, nudiflorin, and several allergenic compounds. This review mainly focuses on the most toxic protein, ricin D, classified as a type 2 ribosome-inactivating protein (RIP2). Ricin is one of the most potent and lethal substances known. It has been considered as an important bioweapon (categorized as a Category B agent (second-highest priority)) and an attractive agent for bioterroristic activities. On the other hand, ricin presents great potential, e.g., as an anti-cancer agent or in cell-based research, and is even explored in the context of nanoparticle formulations in tumor therapy. This review provides a comprehensive overview of the pharmacology and toxicology-related body of knowledge on ricin. Toxicokinetic/toxicodynamic aspects of ricin poisoning and possibilities for analytical detection and therapeutic use are summarized as well.
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Affiliation(s)
- Heike Franke
- Rudolf-Boehm-Institute of Pharmacology and Toxicology, Medical Faculty, University of Leipzig, Haertelstrasse 16-18, 04107, Leipzig, Germany.
| | - Reinhold Scholl
- Department of History, University of Leipzig, Leipzig, Germany
| | - Achim Aigner
- Rudolf-Boehm-Institute of Pharmacology and Toxicology, Clinical Pharmacology, Medical Faculty, University of Leipzig, Leipzig, Germany
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23
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Sequencing of Chinese castor lines reveals genetic signatures of selection and yield-associated loci. Nat Commun 2019; 10:3418. [PMID: 31366935 PMCID: PMC6668449 DOI: 10.1038/s41467-019-11228-3] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2019] [Accepted: 06/27/2019] [Indexed: 02/06/2023] Open
Abstract
Oil produced by castor (Ricinus communis) has broad industrial applications. However, knowledge on the genetic diversity, especially genetic alterations that occurred during domestication and subsequent traits selection, of this oil crop is limited. Here, our population genomics analyses show that the Chinese castors have developed a geographic pattern, classified into the southern-, the middle-, and the northern-China groups. We detect a number of candidate genomic loci that are associated with the selection signals during the geographical differentiation and domestication. Using genome-wide association analysis, we identify candidate genes associated with nine agronomically important traits. One of the candidate genes encoding a glycosyltransferase related to cellulose and lignin biosynthesis is associated with both capsule dehiscence and endocarp thickness. We hypothesize that the abundance of cellulose or lignin in endocarp is an important factor for capsule dehiscence. Our results provide foundation for castor breeding and genetic study. Castor is an important industrial oil crop, but knowledge on its genetic diversity is limited. Here, Fan et al. show geographic pattern of Chinese castors that have developed during domestication by population genetic analyses, and reveal candidate genes associated with agronomically important traits.
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24
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Pan S, Hou D, Yang G, Xie Q, Yan S, Zeng Q, Wang Z, Chen Y, Fan H. Epoxidized methyl ricinoleate bio-plasticizer with a pendant acetate ester for PVC artificial material: circumventing existing limit on achievable migration resistance. JOURNAL OF LEATHER SCIENCE AND ENGINEERING 2019. [DOI: 10.1186/s42825-019-0006-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
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25
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Isenberg SL, Carter MD, Miller MA, Noras AI, Mojica MA, Carlson ST, Bulathsinghala CP, Thomas JD, Johnson RC. Quantification of Ricinine and Abrine in Human Plasma by HPLC-MS-MS: Biomarkers of Exposure to Ricin and Abrin. J Anal Toxicol 2018; 42:630-636. [PMID: 29931062 PMCID: PMC6214751 DOI: 10.1093/jat/bky040] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2018] [Accepted: 05/30/2018] [Indexed: 12/25/2022] Open
Abstract
Ricin and abrin are toxic ribosome-inactivating proteins found in plants. Exposure to these toxins can be detected using the biomarkers ricinine and abrine, which are present in the same plant sources as the toxins. The concentration of the biomarkers in urine and blood will be dependent upon the purification of abrin or ricin, the route of exposure, and the length of time between exposure and sample collection. Here, we present the first diagnostic assay for the simultaneous quantification of both ricinine and abrine in blood matrices. Furthermore, this is the first-ever method for the detection of abrine in blood products. Samples were processed by isotope-dilution, solid-phase extraction, protein precipitation and quantification by HPLC-MS-MS. This analytical method detects abrine from 5.00 to 500 ng/mL and ricinine from 0.300 to 300 ng/mL with coefficients of determination of 0.996 ± 0.003 and 0.998 ± 0.002 (n = 22), respectively. Quality control material accuracy was determined to have <10% relative error, and precision was within 19% relative standard deviation. The assay's time-to-first result is three hours including sample preparation. Furthermore, the method was applied for the quantification of ricinine in the blood of a patient who had intentionally ingested castor beans to demonstrate the test was fit-for-purpose. This assay was designed to support the diagnosis of ricin and abrin exposures in public health investigations.
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Affiliation(s)
- Samantha L. Isenberg
- Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA
| | - Melissa D. Carter
- Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA
| | - Michael A. Miller
- Department of Emergency Medicine, Texas A&M, Christus Spohn Emergency Medicine Residency Program, Corpus Christi, TX
| | - Aleksandra I. Noras
- Oak Ridge Institute for Science and Education at the Centers for Disease Control and Prevention, Atlanta, GA
| | - Mike A. Mojica
- Battelle Memorial Institute at the Centers for Disease Control and Prevention, Atlanta, GA
| | - Sean T. Carlson
- Department of Emergency Medicine, Texas A&M, Christus Spohn Emergency Medicine Residency Program, Corpus Christi, TX
| | | | - Jerry D. Thomas
- Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA
| | - Rudolph C. Johnson
- Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA
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26
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The role of edible oils in low molecular weight organogels rheology and structure. Food Res Int 2018; 111:399-407. [DOI: 10.1016/j.foodres.2018.05.050] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2018] [Revised: 04/30/2018] [Accepted: 05/21/2018] [Indexed: 11/19/2022]
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27
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Singh D, Fisher J, Shagalov D, Varma A, Siegel DM. Dangerous plants in dermatology: Legal and controlled. Clin Dermatol 2018; 36:399-419. [PMID: 29908582 DOI: 10.1016/j.clindermatol.2018.03.013] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
The plant and mushroom kingdoms have species used for intoxication, inebriation, or recreation. Some of these species are toxic. Given that many of these plants or substances are illegal and have histories of abuse, much of the research regarding therapeutic application is based on basic science, animal studies, and traditional use. This review examines Cannabis, Euphorbia, Ricinus, Podophyllum, Veratrum, mushrooms, and nightshades, along with resveratrol and cocaine as they relate to dermatology.
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Affiliation(s)
- Deeptej Singh
- Department of Dermatology, University of New Mexico School of Medicine, Albuquerque, NM.
| | - Juliya Fisher
- Department of Dermatology, SUNY Downstate Medical Center, Brooklyn, NY
| | - Devorah Shagalov
- Department of Dermatology, SUNY Downstate Medical Center, Brooklyn, NY
| | - Aakaash Varma
- Department of Dermatology, SUNY Downstate Medical Center, Brooklyn, NY
| | - Daniel M Siegel
- Department of Dermatology, SUNY Downstate Medical Center, Brooklyn, NY
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28
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Barbosa ASL, Guedes JDS, da Silva DR, Meneghetti SMP, Meneghetti MR, da Silva AE, de Araujo MV, Alexandre-Moreira MS, de Aquino TM, de Siqueira Junior JP, de Araújo RSA, da Cruz RMD, Mendonça-Junior FJB. Synthesis and evaluation of the antibiotic and adjuvant antibiotic potential of organotin(IV) derivatives. J Inorg Biochem 2017; 180:80-88. [PMID: 29247870 DOI: 10.1016/j.jinorgbio.2017.12.004] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2017] [Revised: 12/04/2017] [Accepted: 12/05/2017] [Indexed: 12/31/2022]
Abstract
A series of organotin(IV) derivatives was investigated in vitro for their antibiotic and adjuvant antibiotic properties (efflux pump inhibitors) against Staphylococcus aureus strains that overexpress efflux pump proteins for norfloxacin (SA-1199B), erythromycin (RN-4220) and tetracycline (IS-58). Most organotin(IV) compounds showed significant antibacterial activity with small Minimum Inhibitory Concentration (MIC) values, some of which were close to 1.0μg/mL (3.1μM), but this feature was also associated with substantial cytotoxicity. Nevertheless, the cytotoxicity of these organotin(IV) compounds can be overcome when they are used as antibiotic adjuvants. Their remarkable adjuvant antibiotic properties allow potentiation of the action of tetracycline (against IS-58 strain) by up to 128-fold. This likely indicates that they can act as putative inhibitors of bacterial efflux pumps. These results reinforce organotin(IV) complexes as promising antibacterial agents, and many of these complexes, if associated with antibiotics, can act as potential adjuvant antibiotic candidates.
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Affiliation(s)
- Ana Soraya Lima Barbosa
- Group of Catalysis and Chemical Reactivity, Institute of Chemistry and Biotechnology, Federal University of Alagoas, 57072-970 Maceió, AL, Brazil
| | - Jéssica de Siqueira Guedes
- Group of Catalysis and Chemical Reactivity, Institute of Chemistry and Biotechnology, Federal University of Alagoas, 57072-970 Maceió, AL, Brazil
| | - Douglas Rozendo da Silva
- Group of Catalysis and Chemical Reactivity, Institute of Chemistry and Biotechnology, Federal University of Alagoas, 57072-970 Maceió, AL, Brazil
| | - Simoni Margareti Plentz Meneghetti
- Group of Catalysis and Chemical Reactivity, Institute of Chemistry and Biotechnology, Federal University of Alagoas, 57072-970 Maceió, AL, Brazil
| | - Mario Roberto Meneghetti
- Group of Catalysis and Chemical Reactivity, Institute of Chemistry and Biotechnology, Federal University of Alagoas, 57072-970 Maceió, AL, Brazil.
| | - Amanda Evelyn da Silva
- Laboratory of Pharmacology and Immunity, Institute of Biological Sciences and Health, Federal University of Alagoas, 57020-720 Maceió, AL, Brazil
| | - Morgana Vital de Araujo
- Laboratory of Pharmacology and Immunity, Institute of Biological Sciences and Health, Federal University of Alagoas, 57020-720 Maceió, AL, Brazil
| | - Magna Suzana Alexandre-Moreira
- Laboratory of Pharmacology and Immunity, Institute of Biological Sciences and Health, Federal University of Alagoas, 57020-720 Maceió, AL, Brazil
| | - Thiago Mendonça de Aquino
- Group of Catalysis and Chemical Reactivity, Institute of Chemistry and Biotechnology, Federal University of Alagoas, 57072-970 Maceió, AL, Brazil; Nucleus of Analysis and Research in Nuclear Magnetic Resonance - NAPRMN, Institute of Chemistry and Biotechnology, Federal University of Alagoas, 57020-720 Maceió, AL, Brazil
| | | | - Rodrigo Santos Aquino de Araújo
- Laboratory of Synthesis and Drug Delivery, Biological Science Department, State University of Paraiba, 58071-160 João Pessoa, PB, Brazil
| | - Ryldene Marques Duarte da Cruz
- Graduate Program in Natural and Synthetic Bioactive Products, Federal University of Paraiba, 58071-160 João Pessoa, PB, Brazil
| | - Francisco Jaime Bezerra Mendonça-Junior
- Laboratory of Synthesis and Drug Delivery, Biological Science Department, State University of Paraiba, 58071-160 João Pessoa, PB, Brazil; Graduate Program in Natural and Synthetic Bioactive Products, Federal University of Paraiba, 58071-160 João Pessoa, PB, Brazil.
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Mani Rathnam V, Lamba N, Madras G. Evaluation of new density based model to correlate the solubilities of ricinoleic acid, methyl ricinoleate and methyl 10-undecenoate in supercritical carbon dioxide. J Supercrit Fluids 2017. [DOI: 10.1016/j.supflu.2017.07.017] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Shields PG, Berman M, Brasky TM, Freudenheim JL, Mathe E, McElroy JP, Song MA, Wewers MD. A Review of Pulmonary Toxicity of Electronic Cigarettes in the Context of Smoking: A Focus on Inflammation. Cancer Epidemiol Biomarkers Prev 2017; 26:1175-1191. [PMID: 28642230 PMCID: PMC5614602 DOI: 10.1158/1055-9965.epi-17-0358] [Citation(s) in RCA: 81] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2017] [Revised: 05/22/2017] [Accepted: 05/24/2017] [Indexed: 12/30/2022] Open
Abstract
The use of electronic cigarettes (e-cigs) is increasing rapidly, but their effects on lung toxicity are largely unknown. Smoking is a well-established cause of lung cancer and respiratory disease, in part through inflammation. It is plausible that e-cig use might affect similar inflammatory pathways. E-cigs are used by some smokers as an aid for quitting or smoking reduction, and by never smokers (e.g., adolescents and young adults). The relative effects for impacting disease risk may differ for these groups. Cell culture and experimental animal data indicate that e-cigs have the potential for inducing inflammation, albeit much less than smoking. Human studies show that e-cig use in smokers is associated with substantial reductions in blood or urinary biomarkers of tobacco toxicants when completely switching and somewhat for dual use. However, the extent to which these biomarkers are surrogates for potential lung toxicity remains unclear. The FDA now has regulatory authority over e-cigs and can regulate product and e-liquid design features, such as nicotine content and delivery, voltage, e-liquid formulations, and flavors. All of these factors may impact pulmonary toxicity. This review summarizes current data on pulmonary inflammation related to both smoking and e-cig use, with a focus on human lung biomarkers. Cancer Epidemiol Biomarkers Prev; 26(8); 1175-91. ©2017 AACR.
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Affiliation(s)
- Peter G Shields
- Comprehensive Cancer Center, The Ohio State University and James Cancer Hospital, and College of Medicine, Columbus, Ohio.
| | - Micah Berman
- Comprehensive Cancer Center, The Ohio State University and James Cancer Hospital, and College of Public Health, Ohio
| | - Theodore M Brasky
- Comprehensive Cancer Center, The Ohio State University and James Cancer Hospital, and College of Medicine, Columbus, Ohio
| | - Jo L Freudenheim
- Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, University at Buffalo, Buffalo, New York
| | - Ewy Mathe
- Department of Biomedical Informatics, The Ohio State University, Columbus, Ohio
| | - Joseph P McElroy
- Center for Biostatistics, Department of Biomedical Informatics, The Ohio State University, Columbus, Ohio
| | - Min-Ae Song
- Comprehensive Cancer Center, The Ohio State University and James Cancer Hospital, and College of Medicine, Columbus, Ohio
| | - Mark D Wewers
- Department of Internal Medicine, The Ohio State University, Columbus, Ohio
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Formiga RDO, Quirino ZGM, Diniz MDFFM, Marinho AF, Tavares JF, Batista LM. Maytenus erythroxylon Reissek (Celastraceae) ethanol extract presents antidiarrheal activity via antimotility and antisecretory mechanisms. World J Gastroenterol 2017; 23:4381-4389. [PMID: 28706420 PMCID: PMC5487501 DOI: 10.3748/wjg.v23.i24.4381] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2016] [Revised: 02/24/2017] [Accepted: 03/15/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the acute toxicity, phytochemical profile, antidiarrheal activity and mechanisms of action of Maytenus erythroxylon (M. erythroxylon) ethanol extract.
METHODS A castor oil-induced diarrhea model was used to evaluate antidiarrheal activity. Intestinal transit and gastric emptying protocols were used to evaluate a possible antimotility effect. KATP channels, nitric oxide, presynaptic α2-adrenergic and tissue adrenergic receptors were investigated to uncover antimotility mechanisms of action and castor oil-induced enteropooling to elucidate antisecretory mechanisms.
RESULTS All tested doses of the extract (62.5, 125, 250 and 500 mg/kg) possessed antidiarrheal activity, with a significant decrease of the evacuation index. This activity is possibly related to a reduced gastric emptying (125, 250 and 500 mg/kg) and to a decreased percentage of intestinal transit for all tested doses. That last effect seems to be modulated by nitric oxide, KATP channels and tissue adrenergic receptors. Besides, the extract also presented antisecretory effect due to a decrease of intestinal fluid accumulation.
CONCLUSION The antidiarrheal effect of M. erythroxylon found in this study involves antimotility and antisecretory mechanisms that may be attributed to the chemical compounds found in this species: saponins, flavonoids, tannins, triterpenes and steroids.
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Neri I, Dante G, Pignatti L, Salvioli C, Facchinetti F. Castor oil for induction of labour: a retrospective study. J Matern Fetal Neonatal Med 2017; 31:2105-2108. [PMID: 28618920 DOI: 10.1080/14767058.2017.1336223] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
PURPOSE The aim of this study is to investigate the safety and efficacy of castor oil to induce labour. MATERIALS AND METHODS A retrospective observational case control study was conducted over five years. Castor oil was proposed to women referred to the Birth Centre (Castor Oil group (COG)). They were compared to women who chose to be followed by the traditional doctor-led unit (control group (CG)). Castor oil was administered in a 60 ml single dose in 200 ml of warm water. Inclusion criteria were gestational age between 40 and 41 weeks plus premature rupture of membranes between 12 and 18 hours or amniotic fluid index ≤4 or Bishop Score of ≤4 or absence of spontaneous labour over 41 + 4 weeks. RESULTS Pharmacological induction of labour was required for 18 women in the COG (45%) and 36 in the CG (90%) (p < .001). The mode of delivery differed significantly between groups: women assuming castor oil showed a higher incidence of vaginal delivery, whereas the incidence of caesarean section was lower in the COG, but no statistical significance was reached. CONCLUSIONS The use of castor oil is related to a higher probability of labour initiation within 24 hours. Castor oil can be considered a safe non-pharmacological method for labour induction.
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Affiliation(s)
- Isabella Neri
- a Mother-Infant Department , University of Modena and Reggio Emilia , Modena , Italy
| | - Giulia Dante
- a Mother-Infant Department , University of Modena and Reggio Emilia , Modena , Italy
| | - Lucrezia Pignatti
- a Mother-Infant Department , University of Modena and Reggio Emilia , Modena , Italy
| | - Chiara Salvioli
- a Mother-Infant Department , University of Modena and Reggio Emilia , Modena , Italy
| | - Fabio Facchinetti
- a Mother-Infant Department , University of Modena and Reggio Emilia , Modena , Italy
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Thermosensitive Hydrogel Mask Significantly Improves Skin Moisture and Skin Tone; Bilateral Clinical Trial. COSMETICS 2017. [DOI: 10.3390/cosmetics4020017] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
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Abstract
Imagine a scenario where personal belongings such as pens, keys, phones, or handbags are found at an investigative site. It is often valuable to the investigative team that is trying to trace back the belongings to an individual to understand their personal habits, even when DNA evidence is also available. Here, we develop an approach to translate chemistries recovered from personal objects such as phones into a lifestyle sketch of the owner, using mass spectrometry and informatics approaches. Our results show that phones' chemistries reflect a personalized lifestyle profile. The collective repertoire of molecules found on these objects provides a sketch of the lifestyle of an individual by highlighting the type of hygiene/beauty products the person uses, diet, medical status, and even the location where this person may have been. These findings introduce an additional form of trace evidence from skin-associated lifestyle chemicals found on personal belongings. Such information could help a criminal investigator narrowing down the owner of an object found at a crime scene, such as a suspect or missing person.
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Vance DJ, Mantis NJ. Progress and challenges associated with the development of ricin toxin subunit vaccines. Expert Rev Vaccines 2016; 15:1213-22. [PMID: 26998662 PMCID: PMC5193006 DOI: 10.1586/14760584.2016.1168701] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
The past several years have seen major advances in the development of a safe and efficacious ricin toxin vaccine, including the completion of two Phase I clinical trials with two different recombinant A subunit (RTA)-based vaccines: RiVax™ and RVEc™ adsorbed to aluminum salt adjuvant, as well as a non-human primate study demonstrating that parenteral immunization with RiVax elicits a serum antibody response that was sufficient to protect against a lethal dose aerosolized ricin exposure. One of the major obstacles moving forward is assessing vaccine efficacy in humans, when neither ricin-specific serum IgG endpoint titers nor toxin-neutralizing antibody levels are accepted as definitive predictors of protective immunity. In this review we summarize ongoing efforts to leverage recent advances in our understanding of RTA-antibody interactions at the structural level to develop novel assays to predict vaccine efficacy in humans.
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Affiliation(s)
- David J. Vance
- Division of Infectious Disease, Wadsworth Center, New York State Department of Health, Albany, New York, USA
| | - Nicholas J. Mantis
- Division of Infectious Disease, Wadsworth Center, New York State Department of Health, Albany, New York, USA
- Department of Biomedical Sciences, University at Albany, Albany, New York, USA
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Management of Castor Bean Seed-Associated Intraventricular Hemorrhage with Fresh Frozen Plasma: A Case Report. IRANIAN RED CRESCENT MEDICAL JOURNAL 2016. [DOI: 10.5812/ircmj.27834] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
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Al-Mamun MA, Akter Z, Uddin MJ, Ferdaus KMKB, Hoque KMF, Ferdousi Z, Reza MA. Characterization and evaluation of antibacterial and antiproliferative activities of crude protein extracts isolated from the seed of Ricinus communis in Bangladesh. BMC COMPLEMENTARY AND ALTERNATIVE MEDICINE 2016; 16:211. [PMID: 27405609 PMCID: PMC4942971 DOI: 10.1186/s12906-016-1185-y] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/15/2016] [Accepted: 07/01/2016] [Indexed: 12/15/2022]
Abstract
BACKGROUND Ricinus communis (Euphorbiaceae) has previously been reported to possess analgesic, antihistamine, antioxidant and anti-inflammatory activities. This study was designed for isolation, characterization and evaluation of antibacterial and anti-proliferative activities of R. communis seed protein. METHODS The concentration and molecular weight of R. communis seed protein were estimated by SDS-PAGE and spectrophotometric analysis, respectively. Lectin activity was evaluated by hemagglutination assay on mice blood. In vitro susceptibility of four human pathogenic bacteria including Escherichia coli, Pseudomonas aeruginosa, Enterobacter aerogenes and Staphylococcus aureus was detected using disk diffusion assay, and minimum inhibitory concentration (MIC) value was determined using micro-dilution method. A total of twenty four Swiss albino mice containing Ehrlich's ascites carcinoma (EAC) cells were treated with the crude protein of R. communis at 50 and 100 μg/ml/d/mouse for 6 days. Growth inhibitory activity of R. communis seed protein on EAC cells was determined by haemocytometer counting using trypan blue dye and DAPI (4΄,6-diamidino-2-phenylindole) staining was used to assess apoptotic cells. RESULTS The protein concentration of six R. communis (castor) varieties ranged between 21-35 mg/ml and molecular weight between 14-200 kDa. Castor protein agglutinated mice blood at 3.125 μg/wall. The seed protein shows considerable antimicrobial activity against E. coli, P. aeruginosa and S. aureus, exhibiting MIC values of 250, 125 and 62.5 μg/ml, respectively. Administration of seed protein led to 54 % growth inhibition of EAC cells at 100 μg/ml. DAPI staining indicates marked features of apoptosis including condensation of cytoplasm, nuclear fragmentation and aggregation of apoptotic bodies etc. CONCLUSION Our study suggests that the lectin rich R. communis seed protein has strong antibacterial and anticancer activities.
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Affiliation(s)
- M Abdulla Al-Mamun
- Department of Genetic Engineering and Biotechnology, Protein Science Lab, University of Rajshahi, Rajshahi, 6205, Bangladesh
| | - Zerin Akter
- Department of Genetic Engineering and Biotechnology, Protein Science Lab, University of Rajshahi, Rajshahi, 6205, Bangladesh
| | - Md Josim Uddin
- Department of Pharmacy, Faculty of Science and Engineering, International Islamic University Chittagong, Chittagong, 4203, Bangladesh
| | - K M K B Ferdaus
- Department of Genetic Engineering and Biotechnology, Protein Science Lab, University of Rajshahi, Rajshahi, 6205, Bangladesh
| | - K M F Hoque
- Department of Genetic Engineering and Biotechnology, Protein Science Lab, University of Rajshahi, Rajshahi, 6205, Bangladesh
| | - Z Ferdousi
- Department of Genetic Engineering and Biotechnology, Protein Science Lab, University of Rajshahi, Rajshahi, 6205, Bangladesh
| | - M Abu Reza
- Department of Genetic Engineering and Biotechnology, Protein Science Lab, University of Rajshahi, Rajshahi, 6205, Bangladesh.
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Di Tommaso C, Bourges JL, Valamanesh F, Trubitsyn G, Torriglia A, Jeanny JC, Behar-Cohen F, Gurny R, Möller M. Novel micelle carriers for cyclosporin A topical ocular delivery: in vivo cornea penetration, ocular distribution and efficacy studies. Eur J Pharm Biopharm 2012; 81:257-264. [PMID: 22445900 DOI: 10.1016/j.ejpb.2012.02.014] [Citation(s) in RCA: 97] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2011] [Revised: 02/22/2012] [Accepted: 02/23/2012] [Indexed: 11/26/2022]
Abstract
Cornea transplantation is one of the most performed graft procedures worldwide with an impressive success rate of 90%. However, for "high-risk" patients with particular ocular diseases in addition to the required surgery, the success rate is drastically reduced to 50%. In these cases, cyclosporin A (CsA) is frequently used to prevent the cornea rejection by a systemic treatment with possible systemic side effects for the patients. To overcome these problems, it is a challenge to prepare well-tolerated topical CsA formulations. Normally high amounts of oils or surfactants are needed for the solubilization of the very hydrophobic CsA. Furthermore, it is in general difficult to obtain ocular therapeutic drug levels with topical instillations due to the corneal barriers that efficiently protect the intraocular structures from foreign substances thus also from drugs. The aim of this study was to investigate in vivo the effects of a novel CsA topical aqueous formulation. This formulation was based on nanosized polymeric micelles as drug carriers. An established rat model for the prevention of cornea graft rejection after a keratoplasty procedure was used. After instillation of the novel formulation with fluorescent labeled micelles, confocal analysis of flat-mounted corneas clearly showed that the nanosized carriers were able to penetrate into all corneal layers. The efficacy of a 0.5% CsA micelle formulation was tested and compared to a physiological saline solution and to a systemic administration of CsA. In our studies, the topical CsA treatment was carried out for 14 days, and the three parameters (a) cornea transparency, (b) edema, and (c) neovascularization were evaluated by clinical observation and scoring. Compared to the control group, the treated group showed a significant higher cornea transparency and significant lower edema after 7 and 13 days of the surgery. At the end point of the study, the neovascularization was reduced by 50% in the CsA-micelle treated animals. The success rate of cornea graft transplantation was 73% in treated animals against 25% for the control group. This result was as good as observed for a systemic CsA treatment in the same animal model. This new formulation has the same efficacy like a systemic treatment but without the serious CsA systemic side effects. Ocular drug levels of transplanted and healthy rat eyes were dosed by UPLC/MS and showed a high CsA value in the cornea (11710 ± 7530 ng(CsA)/g(tissue) and 6470 ± 1730 ng(CsA)/g(tissue), respectively). In conclusion, the applied formulation has the capacity to overcome the ocular surface barriers, the micelles formed a drug reservoir in the cornea from, where a sustained release of CsA can take place. This novel formulation for topical application of CsA is clearly an effective and well-tolerated alternative to the systemic treatment for the prevention of corneal graft rejection.
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Affiliation(s)
- Claudia Di Tommaso
- School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Geneva, Switzerland
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Worbs S, Köhler K, Pauly D, Avondet MA, Schaer M, Dorner MB, Dorner BG. Ricinus communis intoxications in human and veterinary medicine-a summary of real cases. Toxins (Basel) 2011; 3:1332-72. [PMID: 22069699 PMCID: PMC3210461 DOI: 10.3390/toxins3101332] [Citation(s) in RCA: 118] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2011] [Revised: 09/26/2011] [Accepted: 09/30/2011] [Indexed: 12/11/2022] Open
Abstract
Accidental and intended Ricinus communis intoxications in humans and animals have been known for centuries but the causative agent remained elusive until 1888 when Stillmark attributed the toxicity to the lectin ricin. Ricinus communis is grown worldwide on an industrial scale for the production of castor oil. As by-product in castor oil production ricin is mass produced above 1 million tons per year. On the basis of its availability, toxicity, ease of preparation and the current lack of medical countermeasures, ricin has gained attention as potential biological warfare agent. The seeds also contain the less toxic, but highly homologous Ricinus communis agglutinin and the alkaloid ricinine, and especially the latter can be used to track intoxications. After oil extraction and detoxification, the defatted press cake is used as organic fertilizer and as low-value feed. In this context there have been sporadic reports from different countries describing animal intoxications after uptake of obviously insufficiently detoxified fertilizer. Observations in Germany over several years, however, have led us to speculate that the detoxification process is not always performed thoroughly and controlled, calling for international regulations which clearly state a ricin threshold in fertilizer. In this review we summarize knowledge on intended and unintended poisoning with ricin or castor seeds both in humans and animals, with a particular emphasis on intoxications due to improperly detoxified castor bean meal and forensic analysis.
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Affiliation(s)
- Sylvia Worbs
- Centre for Biological Security, Microbial Toxins (ZBS3), Robert Koch-Institut, Nordufer 20, Berlin 13353, Germany; (S.W.); (D.P.); (M.B.D.)
| | - Kernt Köhler
- Institute of Veterinary Pathology, Justus Liebig University Giessen, Frankfurter Street 96, Giessen 35392, Germany;
| | - Diana Pauly
- Centre for Biological Security, Microbial Toxins (ZBS3), Robert Koch-Institut, Nordufer 20, Berlin 13353, Germany; (S.W.); (D.P.); (M.B.D.)
| | - Marc-André Avondet
- Biology and Chemistry Section, Federal Department of Defence, Civil Protection and Sports DDPS SPIEZ LABORATORY, Austrasse 1, Spiez CH-3700, Switzerland; (M.-A.A.); (M.S.)
| | - Martin Schaer
- Biology and Chemistry Section, Federal Department of Defence, Civil Protection and Sports DDPS SPIEZ LABORATORY, Austrasse 1, Spiez CH-3700, Switzerland; (M.-A.A.); (M.S.)
| | - Martin B. Dorner
- Centre for Biological Security, Microbial Toxins (ZBS3), Robert Koch-Institut, Nordufer 20, Berlin 13353, Germany; (S.W.); (D.P.); (M.B.D.)
| | - Brigitte G. Dorner
- Centre for Biological Security, Microbial Toxins (ZBS3), Robert Koch-Institut, Nordufer 20, Berlin 13353, Germany; (S.W.); (D.P.); (M.B.D.)
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