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A murine model of tuberculosis/type 2 diabetes comorbidity for investigating the microbiome,metabolome and associated immune parameters

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Animal Models and Experimental Medicine 2021年第2期4卷 181-188页

作者： Harindra D.Sathkumara Janet l.Eaton Matt A.Field brenda l.govan Natkunam Ketheesan Andreas Kupz Centre for Molecular Therapeutics Australian Institute of Tropical Health and MedicineJames Cook UniversityCairns&TownsvilleQLDAustralia College of Public Health Medical and Veterinary SciencesJames Cook UniversityTownsvilleQLDAustralia Centre for Tropical Bioinformatics and Molecular Biology James Cook UniversityCairnsQLDAustralia John Curtin School of Medical Research Australian National UniversityCanberraACTAustralia Science and Technology University of New EnglandArmidaleNSWAustralia

Tuberculosis(TB)is one of the deadliest infectious diseases in the *** meta-bolic disease type 2 diabetes(T2D)significantly increases the risk of developing ac-tive *** new TB vaccine candidates and novel therapeutic interventions are required to meet the challenges of global TB *** evidence suggests that the microbiota plays a significant role in how the host responds to infection,in-jury and neoplastic *** models that closely reflect human physiology are crucial in assessing new treatments and to decipher the underlying immunological defects responsible for increased TB susceptibility in comorbid *** this study,using a diet-induced murine T2D model that reflects the etiopathogenesis of clinical T2D and increased TB susceptibility,we investigated how the intestinal microbiota may impact the development of T2D,and how the gut microbial composition changes following a very low-dose aerosol infection with Mycobacterium tuberculosis(Mtb).Our data revealed a substantial intestinal microbiota dysbiosis in T2D mice compared to non-diabetic *** observed differences were comparable to previous clini-cal reports in TB patients,in which it was shown that Mtb infection causes rapid loss of microbial ***,diversity index and principle component analyses demonstrated distinct clustering of Mtb-infected non-diabetic mice ***-infected T2D *** findings support a broad applicability of T2D mice as a tractable small animal model for studying distinct immune parameters,microbiota and the immune-metabolome of TB/T2D *** model may also enable answers to be found to critical outstanding questions about targeted interventions of the gut mi-crobiota and the gut-lung axis.

关键词： gut microbiota host microbe interaction infectious diseases tuberculosis type 2 diabetes

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Molecular and cellular mechanisms of neuroprotection by oligopeptides from snake venoms

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BIOCEll 2024年第6期48卷 897-904页

作者： CARlOS AlBERTO-SIlVA brenda RUFINO DA SIlVA Natural and Humanities Sciences Center Experimental Morphophysiology LaboratoryFederal University of ABC(UFABC)São Bernardo do CampoSão PauloBrazil

Venom snake-derived peptides have multiple biochemical,pharmacological,and toxicological proﬁles,allowing for the discovery of new medicinal products and therapeutic *** review speciﬁcally examines the fundamental elements of neuroprotection offered by different oligopeptides derived from snake *** also includes a brief evaluation of short peptides that are being considered as potential therapeutic ***-rich peptides and tryptophyllin family peptides isolated from the crude venom of Viperidae family snakes,speciﬁcally Bothrops atrox,Bothrops jararaca,and Bothrops moojeni,have been shown to have pro-survival properties,the ability to reduce oxidative stress,and the ability to promote cell viability and mitochondrial *** signiﬁcant mechanisms are related to the neuroprotection mediated by snake venom oligopeptides:(1)Activation of the l-arginine metabolite pathway,such as polyamines from ornithine metabolism,which reduces N-methyl-D-aspartate(NMDA)-type glutamate receptor activity;(2)Enhancement of cell viability by activating the nerve growth factor-signaling pathway;and(3)Activation of the Muscarinic acetylcholine receptor subtype M1(mAChR-M1).These small peptides show promise as neuroprotective agents against a variety of neurodegenerative disorders.

关键词： Neuroprotective peptides Neurodegenerative disease Oxidative stress Reactive oxygen species Biopeptides

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Autoantibodies against beta cells to predict early insulin requirements in pediatric patients with clinically diagnosed type 2 diabetes

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World Journal of Diabetes 2024年第8期15卷 1717-1725页

作者： Jorge M Molina Patricia G Medina Rita A Gomez Julia R Herrera Nancy l Martínez brenda Hernández Yesenia García Department of Endocrinology Children’s Hospital Federico GomezMexico 06720Mexico National Medical Center"Siglo XXI" UMAE Hosp EspecialidadesUnidad Invest Med Epidemiol ClinMexican Social Security InstituteMexico 06720Mexico Research Division UMAE Hospital de EspecialidadesCentro Médico Nacional Siglo XXIMexican Institute of Social SecurityMexico 06720Mexico Epidemiology Research Unit in Endocrinology and Nutrition Federico Gómez Children’s HospitalMexico 06720Mexico Department of Endocrinology Comprehensive Health Unit for Trans PersonsMexico 11340Mexico

BACKGROUND Autoimmunity has emerged as a probable disease modifier in patients with clinically diagnosed type 2 diabetes mellitus(T2DM),that is,patients who have insulin resistance,obesity,and other cardiovascular risk factors,suggesting that the presence of glutamic acid decarboxylase(anti-GAD65),islet antigen 2(anti-IA2),and zinc transporter 8(anti-Zn8T)antibodies could have deleterious effects on beta cell function,causing failure and earlier requirement for insulin *** To evaluate anti-GAD65,anti-IA2 and anti-Zn8T as predictors of early insulin requirement in adolescents with a clinical diagnosis of *** This was a case–control study in patients with clinically diagnosed with T2DM(68 cases and 64 controls with and without early insulin dependence respectively),male and female,aged 12–18 ***,blood pressure,glucose,insulin,C-peptide,glycated hemoglobin A1c,and lipid profiles were *** was used to measure anti-GAD65,anti-IA2,and anti-Zn8T *** statistics,Pearson'sχ2 test,Student's t test,and logistic regression was performed.Plly *** There were 132 patients(53.8%female),with a mean age was 15.9±1.3 years,and there was a disease evolution time of 4.49±0.88 *** presence of anti-GAD65,anti-IA2,and anti-Zn8T positivity was found in 29.5%,18.2%,and 15.9%,*** the groups by early or no insulin dependence showed that the group with insulin had a higher frequency of antibody positivity:anti-GAD65 odds ratio(OR):2.42(1.112–5.303,P=0.026);anti-IA2:OR:1.55(0.859–2.818,P=0.105);and anti-Zn8T:OR:7.32(2.039–26.279,P=0.002).CONClUSION Anti-GAD65 positivity was high in our ***-GAD65 and anti-Zn8T positivity showed a significantly depleted beta cell reserve phenotype,leading to an increased risk of early insulin dependence.

关键词： Diabetes Obesity Adolescents Autoimmunity Beta cell Insulin requirements

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Colon Adenocarcinoma in a Retrograde Intussusception: A Case Report and literature Review

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Open Journal of Gastroenterology 2024年第5期14卷 153-160页

作者： Carlos Hernández Brito Pedro Arredondo Ruiz brenda Paola Sáenz Dávila Arsenio Torres Delgado luis Eduardo Méndez Turrubiates luis Ángel Amezcua Toledo Omar Josué Herrera lópez Surgical Oncology Department Centro Oncol&#243gico Onkolid Veracruz Mexico Clinical Oncology Department Centro Oncol&#243gico Onkolid Veracruz Mexico General and laparoscopic Surgery Corporativo M&#233dico-Quir&#250rgico Torres Veracruz Mexico Radiation Oncology Department Centro Oncol&#243gico Onkolid Veracruz Mexico Radiology Department Centro Oncol&#243gico Onkolid Veracruz Mexico Anatomical Pathology Department Centro Oncol&#243gico Onkolid Veracruz Mexico

Background: Intussusception is defined as a telescoping of a proximal gastrointestinal segment with its mesentery to a distal one, only 5% occur in adults and in colon the probability that it is caused by a malignant disease is up to 65%. Only 1% occurs in a retrograde manner, the rest occur in an anterograde manner. Aim: Describe the clinical presentation of an intussusception in the adult patient as well as its most frequent causes and possible complications that influence decision making for a definitive treatment. Case Presentation: A 66-year-old woman diagnosed with colon adenocarcinoma who underwent elective transverse colectomy and colonic anastomosis with an incidental finding of a transverse colon tumor in a retrograde intussusception was studied. Conclusion: In any adult patient with an intussusception especially in colon a neoplasia should be suspected and the affected segment should be resected without being reduced due to the risk of perforation and tumor dissemination.

关键词： Colon Cancer Colon Adenocarcinoma Colonic Intussusception Intussusception

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Prenatal multiple micronutrient-fortified balanced energy-protein supplementation and newborn telomere length and mitochondrial DNA content: a randomized controlled efficacy trial in rural Burkina Faso

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Food Science and Human Wellness 2024年

作者： Giles T.Hanley-Cook Yuri Bastos-Moreira Dries S.Martens Trenton Dailey-Chwalibóg laeticia Celine Toe brenda de Kok lionel Ouédraogo Alemayehu Argaw Kokeb Tesfamariam Patrick Kolsteren lieven Huybregts Tim S.Nawrot Sarah De Saeger Marthe De Boevre Carl lachat Department of Food Technology， Safety and Health， Faculty of Bioscience Engineering， Ghent University Center of Excellence in Mycotoxicology and Public Health， MYTOXSOUTH~(?) Coordination Unit， Faculty of Pharmaceutical Sciences， Ghent University Centre for Environmental Sciences， Hasselt University Unité Nutrition et Maladies Métaboliques， Institut de Recherche en Sciences de la Santé (IRSS) Centre Muraz Center of Excellence in Mycotoxicology and Public Health， MYTOXSOUTH? Coordination Unit， Faculty of Pharmaceutical Sciences， Ghent University Nutrition， Diets， and Health Unit， Department of Food and Nutrition Policy， International Food Policy Research Institute (IFPRI) Department of Public Health & Primary Care， University of leuven Department of Biotechnology and Food Technology， Faculty of Science， University of Johannesburg， Doornfontein Campus

Background: Evidence regarding the effectiveness of prenatal nutritional supplements has mainly considered anthropometric pregnancy outcomes. The effect on markers of health and disease， such as offspring telomere length (Tl) and mitochondrial DNA content (mtDNAc) is unknown. Objectives: We assessed the efficacy of maternal multiple micronutrient (MMN)-fortified balanced-energy protein (BEP) and iron-folic acid (IFA) supplementation on newborn Tl as a secondary outcome and mtDNAc as a non-declared outcome. Design: We conducted a randomized controlled trial in rural Burkina Faso， among pregnant females (15-40 years old) enrolled at ly (control) throughout pregnancy. Whole arterial blood samples were collected from the umbilical cord of 104 control and 90 intervention group infants， respectively. Average relative Tl and mtDNAc were measured using quantitative polymerase chain reaction. linear regression models were fitted to assess Tl and mtDNAc differences across trial arms. Results: We found that a combined daily MMN-fortified BEP supplement and IFA tablet did not affect newborn Tl [β = -0.010 (95% CI: -0.057， 0.036); P = 0.662] or mtDNAc [β = 0.065 (95% CI: -0.203， 0.073); P = 0.354]， as compared to an IFA tablet alone. These findings were confirmed (P > 0.05) by adjusting the regression models for potential prognostic factors of study outcomes at enrollment. Exploratory analyses indicated higher， but non-significantly different mtDNAc among children born either small-for-gestational age， low birthweight， or preterm. Conclusions: Newborns from mothers who received daily nutritional supplements across gestation did not have different relative Tl or mtDNAc.

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IDO1 in cancer: a Gemini of immune checkpoints

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Cellular & Molecular Immunology 2018年第5期15卷 447-457页

作者： lijie Zhai Erik ladomersky Alicia lenzen brenda Nguyen Ricky Patel Kristen l lauing Meijing Wu Derek A Wainwright Department of Neurological Surgery Northwestern University Department of Pediatrics Northwestern University Division of Hematology Oncology and Stem Cell TransplantationNorthwestern University Ann&Robert H.lurie Children’s Hospital of Chicago Northwestern University Department of Medicine-Hematology/Oncology Northwestern University Department of Microbiology-Immunology Northwestern University Department of MedicineDivision of Hematology and Oncology Northwestern UniversityBrain Tumor InstituteNorthwestern University Robert H.lurie Comprehensive Cancer Center of Northwestern University Northwestern UniversityChicagoIL 60611USA

Indoleamine 2,3-dioxygenase 1(IDO1)is a rate-limiting metabolic enzyme that converts the essential amino acid tryptophan(Trp)into downstream catabolites known as ***,numerous studies have demonstrated that IDO1 is highly expressed in multiple types of human *** studies have further introduced an interesting paradox:while single-agent treatment with IDO1 enzyme inhibitor has a negligible effect on decreasing the established cancer burden,approaches combining select therapies with IDO1 blockade tend to yield a synergistic benefit against tumor growth and/or animal subject *** the high expression of IDO1 among multiple cancer types along with the lack of monotherapeutic efficacy,these data suggest that there is a more complex mechanism of action than previously *** to the dual faces of the astrological Gemini,we highlight the multiple roles of IDO1 and review its canonical association with IDO1-dependent tryptophan metabolism,as well as documented evidence confirming the dispensability of enzyme activity for its immunosuppressive *** gene transcript levels for IDO1 highlight its strong association with T-cell infiltration,but the lack of a universal prognostic significance among all cancer ***,ongoing clinical trials are discussed with consideration of IDO1-targeting strategies that enhance the efficacy of immunotherapy for cancer patients。

关键词： glioblastoma glioma IDO immunosuppression kynurenine immunotherapy melanoma Treg

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Blessing and a curse of outpatient management of delayed graft function

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World Journal of Transplantation 2019年第4期9卷 58-61页

作者： Justin W Blazel Jennifer A Turk brenda l Muth Sandesh Parajuli Division of Nephrology Department of Medicine University of Wisconsin School of Medicine and Public Health

Delayed graft function (DGF) is a common complication occurring most often after deceased donor kidney transplant with several donor characteristics as well as immunologic factors that lead to its development *** patients require dialysis and close kidney function monitoring until sufficient allograft function is *** has resulted in limited options for DGF management,either prolonged hospitalization until graft function improves to the point where dialysis is no longer needed or discharge back to their home dialysis unit with periodic follow up in the transplant *** is associated with a higher risk for acute rejection,premature graft failure,and 30-d readmission;therefore,these patients need close monitoring,immunosuppression management,and prompt allograft biopsy if prolonged DGF is *** may not occur if these patients are discharged back to their home dialysis *** address this issue,the University of Wisconsin-Madison created a clinic in 2011 specialized in outpatient DGF *** clinic was able to successfully reduce hospital length of stay without an increase in 30-d readmission,graft loss,and patient death.

关键词： Delayed graft function Kidney transplantation Immunosuppression Acute rejection Kidney donor profile index Kidney donor risk index Dialysis

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Acceptability of self-collected human papillomavirus specimens in cervical cancer screening: A review

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World Journal of Obstetrics and Gynecology 2014年第3期3卷 90-97页

作者： brenda l Quincy Department of Physician Assistant Studies School of Health Sciences Elon University

Cervical cancer morbidity and mortality is an important public health problem around the world. Some of the barriers to cervical cancer screening include the embar-rassment, discomfort, lack of privacy and time and cost associated with clinician-collected, clinic-based screen-ing with cytology or human papillomavirus tests. Self-collection of a human papillomavirus （HPV） test has been found to be generally more acceptable, less em-barrassing, more comfortable, more private and easy to do and preferred to pelvic examination for cervical cy-tology by many women worldwide. The most common-ly reported limitation to self-collection is a woman’s lack of confdence in her ability to perform it correctly. Self-collected human papillomavirus tests have been shown to be as or more sensitive than cytology or clinician-collected HPV tests. With confidence-building educa-tion about self-collection, it is likely a viable method to extend the reach of screening in high and low-resource areas around the world.

关键词： Cervical cancer Self-collected Human pap-illomavirus Acceptability

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Brunner and Suddarth's Textbook of Medical-Surgical Nursing (Two Volume Set), Twelfth Edition 12th Edition

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2010年

作者： Suzanne C. Smeltzer brenda Bare Janice l. Hinkle Kerry H. Cheever

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Rb1基因第24和25外显子缺失导致低外显性视网膜母细胞瘤

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中华医学遗传学杂志 2002年第5期19卷 370-374页

作者：杜琴江悦华 brenda l.Galli 广州军区广州总医院遗传中心 510010 Department of Cancer&Blood Research

目的　探讨抑癌基因 Rb1大片段缺失与低外显性视网膜母细胞瘤 (low- penetrance retinoblas-toma)家系的相关性。方法　应用定量多重 PCR技术 (quantitative fluorescentmultiplex PCR,QFM- PCR)筛查 Rb1突变。应用长片段聚合酶链反应 (... 详细信息

目的　探讨抑癌基因 Rb1大片段缺失与低外显性视网膜母细胞瘤 (low- penetrance retinoblas-toma)家系的相关性。方法　应用定量多重 PCR技术 (quantitative fluorescentmultiplex PCR,QFM- PCR)筛查 Rb1突变。应用长片段聚合酶链反应 (long fragment PCR)、逆转录聚合酶链反应 (reverse transcrip-tase- PCR,RT- PCR)、亚克隆、直接测序、Western印迹等技术分析 Rb1突变点的特征。结果　发现 1个家族4代 12 2人中 ,共有 18人携带 Rb1第 2 4和 2 5外显子缺失突变 ,而这些高风险的 Rb1突变基因携带者中 ,只有 11人 (39% )形成单眼或双眼视网膜母细胞瘤 (retinoblastoma ,RB) ,比常见的 Rb1基因突变者中有95 %形成 RB的发病率明显较低。该突变的缺失长达 4 kb基因组 DNA。 c DNA、RNA和测序研究证实 ,有174 bp碱基缺失导致 5 8个密码子丢失。 Western印迹检测出一个比正常 RB1蛋白短、相对分子质量 6 0 0 0(约 6 0 0 0 Da)的 RB突变蛋白得以表达。结论　应用 QFM- PCR技术在一个 RB呈低外显性的大家族中发现Rb1第 2 4和 2 5外显子完全缺失。该突变在基因组 DNA、RNA和蛋白质水平的研究结果 ,为遗传性低外显性视网膜母细胞瘤与该段 DNA缺失相关提供了新的依据 ,并为遗传咨询提供了有价值的资料。

关键词：低外显性视网膜母细胞瘤遗传性视网膜母细胞瘤外显率 Rb1基因基因缺失基因突变定量多重PCR技术 RB

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