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Diabetic cardiomyopathy:importance of direct evidence to support the roles of NOD-like receptor protein 3 inflammasome and pyroptosis

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World Journal of Diabetes 2024年第8期15卷 1659-1662页

作者： Lu Cai Yi Tan Md Shahidul islam Michael horowitz Kupper A Wintergerst Pediatric Research institute Departments of PediatricsRadiation OncologyPharmacology and ToxicologyUniversity of LouisvilleWendy Novak Diabetes InstituteNorton Children’s HospitalLouisvilleKY 40202United States Department of Biochemistry School of Life SciencesUniversity of KwaZulu-NatalDurban 4000KwaZulu-NatalSouth Africa Department of Medicine University of AdelaideAdelaide 5005Australia Pediatric Research institute Division of EndocrinologyDepartment of PediatricsWendy Novak Diabetes InstituteNorton Children’s HospitalUniversity of LouisvilleLouisvilleKY 40202United States

Recently,the roles of pyroptosis,a form of cell death induced by activated NODlike receptor protein 3(NLRP3)inflammasome,in the pathogenesis of diabetic cardiomyopathy(DCM)have been extensively ***,most studies have focused mainly on whether diabetes increases the NLRP3 inflammasome and associated pyroptosis in the heart of type 1 or type 2 diabetic rodent models,and whether various medications and natural products prevent the development of DCM,associated with decreased levels of cardiac NLRP3 inflammasome and *** direct link of NLRP3 inflammasome and associated pyroptosis to the pathogenesis of DCM remains unclear based on the limited evidence derived from the available studies,with the approaches of NLRP3 gene silencing or pharmaceutical application of NLRP3 specific *** thus emphasize the requirement for more systematic studies that are designed to provide direct evidence to support the link,given that several studies have provided both direct and indirect evidence under specific *** editorial emphasizes that the current investigation should be circumspect in its conclusion,i.e.,not overemphasizing its role in the pathogenesis of DCM with the fact of only significantly increased expression or activation of NLRP3 inflammasome and pyroptosis in the heart of diabetic rodent *** clear-cut evidence-based causative roles of NLRP3 inflammasome and pyroptosis in the pathogenesis of DCM can help to develop effective and safe medications for the clinical management of DCM,targeting these biomarkers.

关键词： Diabetic cardiomyopathy Nucleotide oligomerization domain NOD-like receptor protein 3 inflammasome Cardiac cell death Pyroptosis

Calcium channels caught in peripheral glia’s tug-of-war on axon regeneration in Drosophila

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Neural Regeneration Research 2025年第2期20卷 475-476页

作者： Jackson Powell Tobias Steinschaden Rose horowitz Yuanquan Song Raymond G.Perelman Center for Cellular and Molecular Therapeutics The Children’s Hospital of PhiladelphiaPhiladelphiaPAUSA The Neuroscience Graduate Group University of PennsylvaniaPhiladelphiaPAUSA Department of Pathology and Laboratory Medicine University of PennsylvaniaPhiladelphiaPAUSA Medical University of Vienna Center for Brain ResearchDepartment of NeuroimmunologyViennaAustria

Neural damage or degeneration is at the crux of many diseases,and treatment of these diseases will require the development of therapeutics to enhance and guide neural *** intrinsic and extrinsic factors dictate a neuron’s ability to regenerate,and the combination of these factors results in the great regenerative capacity of the peripheral nervous system(PNS)and the poor regenerative capacity of the central nervous system(CNS)following *** the core of a neuron’s function is its ability to relay electrochemical signals,and a neuron’s excitability is a key factor in its ability to *** works have focused on the changes in neuronal electrophysiological properties,firing patterns,and ion flux after injury,which differentially activate signaling pathways at the core of *** role of glia in neuron regeneration has long been studied.

关键词： degeneration firing system

Black Garlic as an Antiviral for Herpes Simplex Virus-2 in Lung Cells

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Advances in Bioscience and Biotechnology 2024年第1期15卷 70-89页

作者： Jenna R. horowitz Lee H. Lee Sandra D. Adams Department of Biology Montclair State University Montclair NJ USA

Allicin, an antioxidant, is known for providing garlic with its unique fragrance and taste, as well as for its antimicrobial properties. Black garlic, a fermented form of garlic, contains higher levels of antioxidants than fresh garlic. Antioxidants play a vital role in alleviating cellular stress during viral infections. Viral infections result in oxidative stress through the production of reactive oxidative species (ROS). A prolonged state of oxidative stress can result in cell death, DNA damage, and disease progression. in this study, black garlic extract (BGE) is evaluated for its ability to mitigate cytopathic effects and oxidative stress caused by herpes simplex virus-2 (HSV-2) infections in vitro. Antiviral assays were performed to determine the percent of viral inhibition resulting from treatment with the BGE. ROS-GloTM H2O2 assays were then completed to measure the post-infection ROS levels of BGE-treated virus and cells. The results thus far suggest that BGE may inhibit viral infection and decrease levels of oxidative stress.

关键词： Black Garlic Herpes Simplex Virus-2 Antioxidant Antiviral Allicin

Surgical or medical treatment of obesity-associated type 2 diabetesan increasing clinical conundrum

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World Journal of Diabetes 2024年第10期15卷 2036-2040页

作者： Ryan J Jalleh Karen L Jones Md Shahidul islam Lu Cai Michael horowitz Adelaide Medical School and Centre of Research Excellence in Translating Nutritional Science to Good Health University of Adelaide Endocrine and Metabolic Unit Royal Adelaide HospitalAdelaide 5000South AustraliaAustralia Department of Biochemistry School of Life SciencesUniversity of KwaZulu-NatalDurban 4000KwaZulu-NatalSouth Africa Pediatric Research institute Departments of PediatricsRadiation OncologyPharmacology and ToxicologyUniversity of LouisvilleWendy Novak Diabetes InstituteNorton Children’s HospitalLouisvilleKY 40202United States

in this editorial,we comment on the article by He et al,specifically in relation to the efficacy of bariatric surgery vs glucagon-like peptide-1 receptor agonist(GLP-1RA)therapy in the management of type 2 diabetes(T2D)associated with *** surgery has now also been shown to be safe and effective in pre-teens and teenagers with obesity and T2D,but information on newer GLP-1RAs in these groups is predictably *** older individuals(age>65 years),both bariatric surgery and GLP-1RA therapy improve cardiovascular ***-tric surgery is not infrequently associated with post-operative postprandial hypoglycemia,which is not the case with GLP-1RAs and,paradoxically,there is evidence that GLP-1RAs may reduce both the frequency and severity of postprandial *** trials of the long-term efficacy of bariatric surgery and GLP-1RAs are indicated.

关键词： Glucagon-like peptide-1 Glucagon-like peptide-1 receptor agonist Obesity Diabetes Weight loss Bariatric surgery Metabolic surgery Hypoglycemia

吉西他滨和拓扑替康治疗有治疗史的卵巢或腹膜癌Ⅰ期试验:一项妇科肿瘤协作组研究

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世界核心医学期刊文摘（妇产科学分册） 2006年第5期2卷 49-49页

作者： Fleming G.F Mitchell S horowitz i 李奎

To determine the maximum tolerated dose (MTD) of the combination of gemcitabine and topotecan in women with previously treated epithelial ovarian, peritoneal, or fallopian tube cancer. Methods. Patients with recurrent or persistent cancer after treatment with a platinum and paclitaxel-containing regimen were eligible for this study. initial treatment was gemcitabine at a dose of 800 mg/m2 on days 1, 8, and 15 and topotecan at a dose of 0.5 mg/m2 on days 2- 5, with cycles repeated every 28 days. Dose escalations were planned first for topotecan (Cohort i, Dose Levels 1- 5) then for gemcitabine (Cohort ii, Dose Levels 6- 9) until the MTD was reached. Results. Ten patients received a total of 29 cycles. When none of the first four patients could complete therapy as prescribed due to toxicity, doses for each drug were reduced by 1 day. The next six patients were treated at the modified schedule of gemcitabine days 1 and 8 and topotecan days 2- 4 (Dose Level- 1). Despite this modification, dose-limiting toxicities including neutropenia, thrombocytopenia, and stomatitis occurred at Dose Level- 1, and the study was closed early. Conclusions. At both the initial dose schedule and an attenuated schedule, the combination of gemcitabine and topotecan produced doselimiting toxicities in women with previously treated epithelial ovarian or peritoneal cancer.

关键词：拓扑替康腹膜癌妇科肿瘤剂量限制性毒性剂量水平输卵管癌最大耐受剂量泰素改良方案白细胞

SKY BLUE,RED HEAVENS,AND ORANGE OVER ANCiENT MESOPOTAMiA

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Journal of Ancient Civilizations 2020年第2期35卷 135-146,267页

作者： Wayne horowitz The Hebrew University of Jemsalem

As a child,my classmates and i almost always painted the sky blue in kindergarten and elementary school,and the idea of"blue skies"has become synonymous with happy times now,and good tidings *** how did Ancient Mesopotamians think about the color of the sky,and its daylight and nighttime phenomena?Based on the cuneiform evidence,we first examine ancient concepts of blue and red in the heavens,and finish with evidence indicating the planet,Mars,was seen as the color"fire・red,''that is to say the color of the crayon today labeled"orange."

关键词： planet orange BLUE

Gastroesophageal reflux disease symptoms:Prevalence,sociodemographics and treatment patterns in the adult israeli population

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World Journal of Gastroenterology 2011年第10期17卷 1332-1335页

作者： Menachem Moshkowitz Noya horowitz Zamir Halpern Erwin Santo Department of Gastroenterology Tel-Aviv Sourasky Medical Center and the Sackler Faculty of MedicineTel-Aviv University

AiM： To evaluate the prevalence and sociodemographics of gastroesophageal reflux disease （GERD） symptoms and to identify treatment patterns among GERD patients. METHODS： A telephone survey of a representative sample of the adult israeli population was conducted. The questionnaire included detailed sociodemographics, history of GERD symptoms and the various treatments used. RESULTS： The survey included 2027 subjects. Twice weekly, once weekly and monthly GEP, D symptoms were reported by 8.4%, 12.5% and 21.5% of subjects, respectively. There was no difference in prevalence between men and woman; however, GERD symptoms were significantly more prevalent within the older age group and lower socioeconomic status. Among those reporting weekly symptoms, a quarter did not use any kind of therapy and another quarter used various traditional remedies （e.g. soda, milk, almonds, etc.）. Antacids were used by 35.1%, H2 blockers by 13.2% and PPis by 17.5%. CONCLUSiON： We found that 12.5% of the adult israeli population experience weekly GERD symptoms. GERD prevalence and sociodemographics are similar to those described in other Western countries, and treatment is still suboptimal.

关键词： Gastroesophageal reflux disease Prevalence Sociodemographics

Upper gastrointestinal function and glycemic control in diabetes mellitus

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World Journal of Gastroenterology 2006年第35期12卷 5611-5621页

作者： Reawika Chaikomin Christopher K Rayner Karen L Jones Michael horowitz University of Adelaide Department of Medi-cine Royal Adelaide Hospital North Terrace Adelaide South Australia 5000 Australia

Recent evidence has highlighted the impact of glycemic control on the incidence and progression of diabetic micro- and macrovascular complications, and on cardiovascular risk in the non-diabetic population. Postprandial blood glucose concentrations make a major contribution to overall glycemic control, and are determined in part by upper gastrointestinal function. Conversely, poor glycemic control has an acute, reversible effect on gastrointestinal motility. insights into the mechanisms by which the gut contributes to glycemia have given rise to a number of novel dietary and pharmacological strategies designed to lower postprandial blood glucose concentrations.

关键词： Blood glucose Diabetes mellitus Gastric Emptying Gastrointestinal motility Hyperglycemia

Microfluidics for interrogating live intact tissues

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Microsystems & Nanoengineering 2020年第1期6卷 538-564页

作者： Lisa F.horowitz Adan D.Rodriguez Tyler Ray Albert Folch Department of Bioengineering University of WashingtonSeattleWA 98195USA Department of Mechanical Engineering University of Hawaiʻi at MānoaHonoluluHI 96822USA

The intricate microarchitecture of tissues–the“tissue microenvironment”–is a strong determinant of tissue *** offers an invaluable tool to precisely stimulate,manipulate,and analyze the tissue microenvironment in live tissues and engineer mass transport around and into small tissue *** control is critical in clinical studies,especially where tissue samples are scarce,in analytical sensors,where testing smaller amounts of analytes results in faster,more portable sensors,and in biological experiments,where accurate control of the cellular microenvironment is *** also provides inexpensive multiplexing strategies to address the pressing need to test large quantities of drugs and reagents on a single biopsy specimen,increasing testing accuracy,relevance,and speed while reducing overall diagnostic ***,we review the use of microfluidics to study the physiology and pathophysiology of intact live tissues at sub-millimeter *** categorize uses as either in vitro studies–where a piece of an organism must be excised and introduced into the microfluidic device–or in vivo studies–where whole organisms are small enough to be introduced into microchannels or where a microfluidic device is interfaced with a live tissue surface(*** skin or inside an internal organ or tumor)that forms part of an animal larger than the *** microfluidic systems promise to deliver functional measurements obtained directly on intact tissue–such as the response of tissue to drugs or the analysis of tissue secretions–that cannot be obtained otherwise.

关键词： fluid drugs testing