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Role of IL-10 and TGF-β1 in local immunosuppression in HPV-associated cervical neoplasia

World Journal of Clinical Oncology 2014年第4期5卷 753-763页

作者： Kirvis Torres-Poveda Margarita Bahena-Román Claudia Madrid-González Ana I Burguete-García Víctor Hugo Bermúdez-Morales Oscar Peralta-Zaragoza Vicente Madrid-Marina Chronic Infection and Cancer Division Research Center on Infectious Diseases Instituto Nacional de Salud Pública 62100 Cuernavaca Morelos Mexico

Cervical cancer is a worldwide disease that constitutes a significant public health problem, especially in developing countries, not only due to its high incidence but also because the most affected population comprises women who belong to marginalized socio-economic classes. Clinical and molecular research has identified immunological impairment in squamous intraepithelial cervical lesions and cervical cancer patients. Human Papillomavirus(HPV) has several mechanisms for avoiding the immune system: it down-regulates the expression of interferon and upregulates interleukin(IL)-10and transforming growth factor(TGF)-β1 to produce a local immunosuppressive environment, which, along with altered tumor surface antigens, forms an immunosuppressive network that inhibits the antitumor immune response. In this review we analyzed the available data on several deregulated cellular immune functions in patients with NIC Ⅰ, NIC Ⅱ and NIC Ⅲ and cervical cancer. The effects of immunosuppressive cytokines on innate immune response, T-cell activation and cellular factors that promote tumor cell proliferation in cervical cancer patients are summarized. We discuss the functional consequences of HPV E2, E6, and E7 protein interactions with IL-10 and TGF-β1 promoters in the induction of these cytokines and postulate its effect on the cellular immune response in squamous intraepithelial cervical lesions and cervical cancer patients. This review provides a comprehensive picture of the immunological functions of IL-10 and TGF-β1 in response to HPV in humans.

关键词： Cervical cancer immunosuppression Interleukin-10 Transforming growth factor-β1 Human Papillomavirus

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Liver transplantation during COVID-19: Adaptive measures with future significance

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World Journal of Transplantation 2022年第9期12卷 288-298页

作者： Argyrios Gyftopoulos Ioannis A Ziogas Martin I Montenovo School of Medicine National Kapodistrian University of AthensAthens 14564Greece Department of Surgery University of Colorado Anschutz Medical CampusAuroraCO 80045United States Division of Hepatobiliary Surgery and Liver Transplantation Department of SurgeryVanderbilt University Medical CenterNashvilleTN 37232United States

Following the outbreak of coronavirus disease 2019(COVID-19),a disease caused by the novel severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the field of liver transplantation,along with many other aspects of healthcare,underwent drastic changes.Despite an initial increase in waitlist mortality and a decrease in both living and deceased donor liver transplantation rates,through the implementation of a series of new measures,the transplant community was able to recover by the summer of 2020.Changes in waitlist prioritization,the gradual implementation of telehealth,and immunosuppressive regimen alte-rations amidst concerns regarding more severe disease in immunocompromised patients,were among the changes implemented in an attempt by the transplant community to adapt to the pandemic.More recently,with the advent of the Pfizer BNT162b2 vaccine,a powerful new preventative tool against in-fection,the pandemic is slowly beginning to subside.The pandemic has cert-ainly brought transplant centers around the world to their limits.Despite the unspeakable tragedy,COVID-19 constitutes a valuable lesson for health systems to be more prepared for potential future health crises and for life-saving tran-splantation not to fall behind.

关键词： Liver transplantation COVID-19 SARS-CoV-2 Vaccine immunosuppression Telehealth

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Systemic combined with intravitreal methotrexate for relentless placoid chorioretinitis:A case report

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World Journal of Clinical Cases 2022年第35期10卷 13115-13121页

作者： Lan Luo Wei-Bin Chen Ming-Wei Zhao Heng Miao Department of Ophthalmology&Clinical Center of Optometry Peking University People’s HospitalBeijing 100044China Eye Diseases and Optometry Institute Peking University People's HospitalBeijing 100044China College of Optometry Peking University Health Science CenterBeijing 100191China Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases Peking University People's HospitalBeijing 100044China

BACKGROUND We describe a case of relentless placoid chorioretinitis(RPC)that progressed despite administration of peribulbar and systemic corticosteroids,and was resolved by systemic combined with intravitreal methotrexate.CASE SUMMARY A 16-year-old male reported painless blurred vision and a temporal scotoma in his right eye for one week.Due to widespread distribution and continuous enlargement,multimodal imaging of the lesions led to the diagnosis of RPC.Lesions in the right eye extended despite peribulbar injection of triamcinolone acetonide,but the progression was immediately terminated by a single dose of intravitreal methotrexate.A new fresh lesion occurred in the contralateral eye despite systemic prednisolone but was resolved by oral methotrexate.CONCLUSION Systemic immunosuppressants should be given upon RPC diagnosis.Intravitreal methotrexate immediately halted progression and may be considered for sightthreatening cases as part of the initial therapy.

关键词： immunosuppression Intravitreal Methotrexate Relentless placoid chorioretinitis Systemic Case report

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Translational research and innovation in modern transplant practice:Paradigms from Greece and around the world

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World Journal of Transplantation 2023年第2期13卷 25-27页

作者： Georgios Tsoulfas Ioannis Boletis Vassilios Papalois Department of Transplantation Surgery Aristotle University School of MedicineThessaloniki 54124Greece Department of Nephrology EKPA UniversityAthens 11527Greece Department of Transplant Surgery Imperial College Renal and Transplant CentreLondon W120HSUnited Kingdom

The continuous clinical and technological advances,together with the social,health and economic challenges that the global population faces,have created an environment where the evolution of the field of transplantation is essentially necessary.The goal of this special issue is to provide a picture of the current status of transplantation in Greece as well as in many other countries in Europe and around the world.Authors from Greece and several other countries provide us with valuable insight into their respective areas of transplant expertise,with a main focus on the field of translational research and innovation.The papers that are part of this Special Issue“Translational Research and Innovation and the current status of Transplantation in Greece”have presented innovative and meaningful approaches in modern transplant research and practice.They provide us with a clear overview of the current landscape in transplantation,including liver transplantation in the context of a major pandemic,the evolution of living donor kidney transplantation or the evolution of the effect of hepatitis C virus infection in transplantation,while at the same time explore more recent challenges,such as the issue of frailty in the transplant candidate and the changes brought by newer treatments,such as immunotherapy,in transplant oncology.Additionally,they offer us a glimpse of the effect that technological innovations,such as virtual reality,can have on transplantation,both in terms of clinical and educational aspects.Just as critical is the fact that this Special Issue emphasizes the multidisciplinary,collaborative efforts currently taking place that link transplant research and innovation with other cutting-edge disciplines such as bioengineering,advanced information technology and artificial intelligence.In this Special Issue,in addition to the clinical and research evolution of the field of transplantation,we are witnessing the importance of interdisciplinary collaboration in medicine.

关键词： Translational research Non-alcoholic fatty liver disease Immunotherapy Pandemic Liver transplantation Bioengineering Artificial intelligence immunosuppression Transplant oncology Living donor kidney transplantation

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Spontaneous Rabies in a Stray Bitch after Parturition Induced immunosuppression —Investigating an Impending Outbreak of Rabies with One Health Approach

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World Journal of Vaccines 2016年第1期6卷 1-8页

作者： Omesh Kumar Bharti Hamender Sharma Uppinder Sharma Archana Phull State Intradermal Antirabies Clinic and Research Centre DDU Hospital Shimla Shimla India Dog Sterilization Centre Animal Birth Control Programme MC Shimla Shimla India Veterinary Hospital Kangra India Daily Post Shimla India

Background: Rabies is endemic in India and every half an hour a person dies of this dreaded disease. Stray roaming dogs, mostly unvaccinated, are most dangerous host in spread of rabies in India and in our state of Himachal Pradesh. Timely prophylaxis is the only method to save animal bite victims, including that of rabid dog bite patients. Objectives: Objective of this study was to investigate an impending outbreak of rabies in Shimla town in the absence of life saving rabies immunoglobulins (RIGs) in the market, and to know the source of infection by using one health approach and using epidemiological tools. Methods: On April 7, 2015, there was a sudden surge in cases of suspected rabid dog bites. Impending rabies outbreak was suspected as there were no RIGs available in the market. A rapid Response Team (RRT) consisting of the author, veterinary doctor, dog squad of Municipal Corporation (MC) Shimla along with the vehicles to impound rabid dogs was constituted to investigate the terror spread by two rabid dogs on biting spree in the Shimla Municipality. Results: A total of 18 people were bitten by suspected rabid dogs within three days period. A black bitch and a brown dog, on the identity of affected people, were captured by the dog squad of Municipality next day on April 8, 2015 and taken to Dog Sterilization Centre, Animal Birth Control (ABC) programme, MC Shimla for observation. The most furious Black bitch died of clinically confirmed symptoms of furious rabies after three days. The second rabid dog, brown in color, died after a month of observation due to paralytic dumb rabies. The brain of the brown dog was extracted for Fluorescent Antibody Testing (FAT) at central research Institute (CRI) Kasauli and was found to be positive for FAT. Follow up of patients was 100% by house to house visit and over telephone and no casualty was reported. Conclusion: While we were working on hypothesis of rabid dogs getting the infection from nearby forest about 8 - 10 KM away but on follow up of the patients, they repor

关键词： Human Rabies Dog Rabies Rabies Outbreak Local Rabies Immunoglobulins Anti Rabies Vaccination immunosuppression FAT Testing ONE Health

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Cancer: Tumor Iron Metabolism, Mitochondrial Dysfunction and Tumor immunosuppression;“A Tight Partnership—Was Warburg Correct?”

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Journal of Cancer Therapy 2012年第4期3卷 278-311页

作者： Robert L. Elliott Jonathan F. Head Elliott-Barnett-Head Breast Cancer Research and Treatment Center Baton Rouge USA

Over the last 30 years there have been numerous worldwide investigators involved in cancer research. Billions of dollars have been spent on drug development and cancer research;however, with all of the new agents and modalities of treatment, we have honestly not significantly improved the overall survival of the Stage IV cancer patient. There is and will not be a magic bullet treatment, thus the extensive title of this paper. We are convinced that unless we use multiple innovative therapies in combination with conventional treatment, we will never truly defeat this disease. We have attempted to address this problem by presenting in detail some of these complex mechanisms involved in tumorigenesis, progression, escape, and metastasis. Most investigators have their own special area of interest, but if we are to conquer this scourge, we must develop an extensive, multifaceted, comprehensive approach. Hopefully this article will contribute to awareness and further insight into this very serious and complicated problem, so we can improve quality of life and improve the survival of the Stage IV cancer patient.

关键词： Tumor Iron Metabolism Mitochondrial Iron Metabolism Mitochondrial Dysfunction Tumor immunosuppression Hypoxia Inducible Factor Pseudohypoxia

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Immunosuppressive regimens and outcomes of inflammatory bowel disease patients requiring kidney transplantation

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World Journal of Transplantation 2022年第2期12卷 21-23页

作者： Urvashi Singh Baljit Singh Maria Irene Bellini Department of Surgery Wythenshawe HospitalManchester University Hospitals NHS Foundation TrustManchester M239LTUnited Kingdom Department of Colorectal Surgery University Hospitals LeicesterLeicester LE15WWUnited Kingdom Department of Surgical Sciences Sapienza UniversityRoma 00161Italy

Patients with inflammatory bowel disease(IBD)can develop extra-renal complications and as a result,suffer from end stage renal failure requiring kidney transplantation(KT).A brief review of available literature revealed that IBD patients undergoing KT have shorter overall survival rates compared to their controls.Literature reporting steroid regimens and survival outcomes specific to IBD and post kidney transplant are scarce and these studies have small sample sizes thus making it difficult to draw accurate conclusions.Further research is required in the form of a randomized controlled study to clarify the effect and mechanism of steroid immunosuppression on the prognosis of renal transplant recipients and explore new treatment schemes.

关键词： Inflammatory bowel disease Kidney transplantation Steroids immunosuppression Kidney failure Ulcerative colitis Crohn’s disease

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Tocilizumab in severe COVID-19-A randomized,double-blind,placebo-controlled trial

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Infectious Medicine 2022年第2期1卷 88-94页

作者： Muhammad Irfan Malik Sardar Al Fareed Zafar Fabiha Qayyum Muna Malik Muhammad Sohaib Asghar Muhammad Junaid Tahir Ammarah Arshad Fatima Khalil Hafiza Shafia Naz Mudassar Aslam Jodat Saleem Abdul Aziz Mustafa Usman Azhar Muhammad Naqash Zohaib Yousaf Postgraduate Medical Institute LahorePakistan Lahore General Hospital LahorePakistan Ameer-ud-Din Medical College LahorePakistan Dow University of Health Sciences-Ojha Campus KarachiPakistan Sheikh Zayed Medical College Rahim Yar KhanPakistan Hamad Medical Corporation DohaQatar

Background:The therapeutic effectiveness of interleukin-6 receptor inhibitor in critically ill hospitalized patients with coronavirus disease 2019(COVID-19)is uncertain.Methods:To evaluate the efficacy and safety of the outcome as recovery or death of tocilizumab for severe acute respiratory syndrome-coronavirus-2(SARS-CoV-2)infection,we conducted a randomized,double-blinded,placebo-controlled phase 2 trial in critically ill COVID-19 adult patients.The patients were randomly assigned in a 4:1 ratio to receive standard medical treatment plus the recommended dose of either tocilizumab or the placebo drug.Randomization was stratified.The primary outcome was the recovery or death after administration of tocilizumab or a placebo drug.The secondary outcomes were clinical recovery or worsening of the patients’symptoms and inflammatory markers and discharge from the hospital.Results:Of 190 patients included in this study,152 received tocilizumab,and 38 received a placebo.The duration of hospital stay of the interventional group was 12.9±9.2,while the placebo group had a more extended hospital stay(15.6±8.8).The mortality ratio for the primary outcome,ie,mortality or recovery in the tocilizumab group was 17.8%;p=0.58 by log-rank test).The mortality ratio in the placebo group was 76.3%;p=0.32 by log-rank test).The inflammatory markers in the tocilizumab group significantly declined by day 16 compared to the placebo group.Conclusions:The use of tocilizumab was associated with decreased mortality,earlier improvement of inflamma-tory markers,and reduced hospital stay in patients with severe COVID-19.

关键词： Inflammatory Infectious immunosuppression COVID-19 Therapy Trial

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Induction of specific immunosuppression of cardiac allograft rejection withmonoclonal antibodies to CD44, LFA-1 and ICAM-1

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Journal of Medical Colleges of PLA(China) 2000年第3期15卷 217-220页

作者：车小燕罗爱武黄洪莲周明乾张亚莉王小宁郭亚军

Objective:To evaluate the immunosuppressive effect of monoclonal antibodies (McAb) against cell surface adhesion molecules on transplant rejection. Methods: C57BL/6 (H-2b) mouse cardiac grafts were transplanted into BALB/c(H- 2d) mice. This model was used to investigate the possibility of immunosuppressive induction with CD44 McAb, leukocyte function associated antigen (LFA-1) and intercellular adhesion molecule (ICAM-1). Results: Treatment of the allograft recipients with CD44 McAb alone, or both LFA-1 and ICAM-1 or combination of these 3 McAb significantly prolonged the cardiac allografts survival as compared with PBS controls (Pimmunosuppression of transplant rejection.

关键词： anti-CD44 anti-LFA-1 anti-ICAM-1 monoclonal antibody allograft rejection immunosuppression

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Immunoregulatory Effects of Nuhuang Fuzheng Granules on Mice with Cytoxan-induced immunosuppression

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Medicinal Plant 2017年第2期8卷 37-39,44页

作者： Chuncheng YU Yifan ZHANG Shaoqin ZHAI Hua ZHENG Maixun ZHU Southwest University Chongqing Academy of Animal Sciences

[Objectives]To study immunoregulatory effects of Nuhuang Fuzheng Granules on mice with Cytoxan-induced immunosuppression.[Methods]Kunming variety mice were randomly divided into the control group,model group,positive medicine group,and low,medium,and high dosage groups of Nuhuang Fuzheng Granules. Except the control group,the rest groups of mice were injected with Cytoxan at60 mg/kg to reproduce the immunosuppressive mice model,and were fed through stomach at 0. 5g/kg,1. 0 g/kg and 2. 0 g/kg Nuhuang Fuzheng Granules for seven days( twice a day); the positive control group was fed with Astragalus Polysacharin( 500 mg/L). The carbon clearance index,immune organ index,serum hemolysin were determined. IL-2,IFN-γ,and IL-4 levels in mouse serum were measured by ELISA. [Results] Nuhuang Fuzheng Granules could significantly incease the carbon granular expurgation index of mice with Cytoxan-induced immunosuppression,and the 2. 0 g/kg and 1. 0 g/kg dosage groups had better effect than 0. 5 g/kg dosage group( P immunosuppression increased significantly and there was dose-effect relationship in a certain range of concentration; the thymus index and serum hemolysin HC_(50) were significantly higher than 0. 5 g/kg dosage group( P 0. 05). [Conclusions] Nuhuang Fuzheng Granules can promote growth of immune organs and secretion of cytokines through improving the carbon granular expurgation ability of mice with Cytoxan-induced immunosuppression.

关键词： Nuhuang Fuzheng Granules Mice with immunosuppression Immunoregulatory effects

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