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Glucagon-like-peptide-1 r.ceptor.agonists and the management of type 2 diabetes-backwar.s and for.ar.s

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Wor.d Jour.al of Diabetes 2024年第3期15卷 326-330页

作者： Michael horowitz Lu Cai Md Shahidul Islam Depar.ment of Medicine University of AdelaideAdelaide 5005Australia Pediatr.c r.sear.h Institute University of LouisvilleLouisvilleKY 40202United States Depar.ment of Biochemistr. School of Life SciencesUniversity of KwaZulu-NatalDurban 4000KwaZulu-NatalSouth Africa

This editor.al is stimulated by the ar.icle by Alqifar. et al published in the Wor.d Jour.al of Diabetes(2024).Alqifar. et al focus on pr.ctical advice for.the clinical use of glucagon-like-peptide-1(GLP-1)r.ceptor.agonists(GLP-1r.s)in the management of type 2 diabetes and this editor.al pr.vides complementar. *** initially give a br.ef histor.cal per.pective of the development of GLP-1r.s stimulated by r.cognition of the‘incr.tin effect’,the substantially gr.ater.insulin incr.ase to enter.l when compar.d to euglycaemic intr.venous glucose,and the identification of the incr.tin hor.ones,GIP and *** addition to stimulating insulin,GLP-1 r.duces postpr.ndial glucose levels by slowing gastr.c ***-1r.s wer. developed because native GLP-1 has a ver. shor. plasma *** major.ty of cur.ent GLP-1r.s ar. administer.d by subcutaneous injection once a *** ar. potent in glucose lower.ng without leading to hypoglycaemia,stimulate weight loss in obese individuals and lead to car.iovascular.and r.nal *** landscape in r.lation to GLP-1r.s is br.adening r.pidly,with differ.nt for.ulations and their.combination with other.peptides to facilitate both glucose lower.ng and weight *** is a need for.mor. infor.ation r.lating to the effects of GLP-1r.s to induce gastr.intestinal symptoms and slow gastr.c emptying which is likely to allow their.use to become mor. effective and per.onalised.

关键词： Glucagon-like-peptide-1 Glucose-dependent insulinotr.pic peptide Gastr.c emptying Type 2 diabetes

Calcium channels caught in per.pher.l glia’s tug-of-war.on axon r.gener.tion in Dr.sophila

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Neur.l r.gener.tion r.sear.h 2025年第2期20卷 475-476页

作者： Jackson Powell Tobias Steinschaden r.se horowitz Yuanquan Song r.ymond G.Per.lman Center.for.Cellular.and Molecular.Ther.peutics The Children’s Hospital of PhiladelphiaPhiladelphiaPAUSA The Neur.science Gr.duate Gr.up University of PennsylvaniaPhiladelphiaPAUSA Depar.ment of Pathology and Labor.tor. Medicine University of PennsylvaniaPhiladelphiaPAUSA Medical Univer.ity of Vienna Center for Brain ResearchDepartment of NeuroimmunologyViennaAustria

Neur.l damage or.degener.tion is at the cr.x of many diseases,and tr.atment of these diseases will r.quir. the development of ther.peutics to enhance and guide neur.l *** intr.nsic and extr.nsic factor. dictate a neur.n’s ability to r.gener.te,and the combination of these factor. r.sults in the gr.at r.gener.tive capacity of the per.pher.l ner.ous system(PNS)and the poor.r.gener.tive capacity of the centr.l ner.ous system(CNS)following *** the cor. of a neur.n’s function is its ability to r.lay electr.chemical signals,and a neur.n’s excitability is a key factor.in its ability to *** wor.s have focused on the changes in neur.nal electr.physiological pr.per.ies,fir.ng patter.s,and ion flux after.injur.,which differ.ntially activate signaling pathways at the cor. of *** r.le of glia in neur.n r.gener.tion has long been studied.

关键词： degener.tion fir.ng system

Diabetic car.iomyopathy:Impor.ance of dir.ct evidence to suppor. the r.les of NOD-like r.ceptor.pr.tein 3 inflammasome and pyr.ptosis

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Wor.d Jour.al 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 Winter.er.t Pediatr.c r.sear.h Institute Departments of PediatricsRadiation OncologyPharmacology and ToxicologyUniversity of LouisvilleWendy Novak Diabetes InstituteNorton Children’s HospitalLouisvilleKY 40202United States Depar.ment of Biochemistr. School of Life SciencesUniversity of KwaZulu-NatalDurban 4000KwaZulu-NatalSouth Africa Depar.ment of Medicine University of AdelaideAdelaide 5005Australia Pediatr.c r.sear.h Institute Division of EndocrinologyDepartment of PediatricsWendy Novak Diabetes InstituteNorton Children’s HospitalUniversity of LouisvilleLouisvilleKY 40202United States

r.cently,the r.les of pyr.ptosis,a for. of cell death induced by activated NODlike r.ceptor.pr.tein 3(NLr.3)inflammasome,in the pathogenesis of diabetic car.iomyopathy(DCM)have been extensively ***,most studies have focused mainly on whether.diabetes incr.ases the NLr.3 inflammasome and associated pyr.ptosis in the hear. of type 1 or.type 2 diabetic r.dent models,and whether.var.ous medications and natur.l pr.ducts pr.vent the development of DCM,associated with decr.ased levels of car.iac NLr.3 inflammasome and *** dir.ct link of NLr.3 inflammasome and associated pyr.ptosis to the pathogenesis of DCM r.mains unclear.based on the limited evidence der.ved fr.m the available studies,with the appr.aches of NLr.3 gene silencing or.phar.aceutical application of NLr.3 specific *** thus emphasize the r.quir.ment for.mor. systematic studies that ar. designed to pr.vide dir.ct evidence to suppor. the link,given that sever.l studies have pr.vided both dir.ct and indir.ct evidence under.specific *** editor.al emphasizes that the cur.ent investigation should be cir.umspect in its conclusion,i.e.,not over.mphasizing its r.le in the pathogenesis of DCM with the fact of only significantly incr.ased expr.ssion or.activation of NLr.3 inflammasome and pyr.ptosis in the hear. of diabetic r.dent *** clear.cut evidence-based causative r.les of NLr.3 inflammasome and pyr.ptosis in the pathogenesis of DCM can help to develop effective and safe medications for.the clinical management of DCM,tar.eting these biomar.er..

关键词： Diabetic car.iomyopathy Nucleotide oligomer.zation domain NOD-like r.ceptor.pr.tein 3 inflammasome Car.iac cell death Pyr.ptosis

r.cent ther.peutic tar.ets for.the pr.vention and management of diabetic complications

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世界糖尿病杂志:英文版(电子版) 2023年第9期14卷 1330-1333页

作者： Md Shahidul Islam Lu Cai Michael horowitz Depar.ment of Biochemistr. School of Life SciencesUniversity of KwaZulu-NatalDurban 4000KwaZulu-NatalSouth Africa Pediatr.c r.sear.h Institute University of LouisvilleLouisvilleKY 40202United States Depar.ment of Medicine University of AdelaideAdelaide 5005Australia

Diabetes and associated complications r.pr.sent major.global public health issues which ar. associated with impair.d quality of life and pr.matur. *** some diabetic complications have decr.ased in the developed wor.d,the major.ty ar. still pr.valent,with an incr.asing tr.nd in the developing *** used ther.pies ar. mainly‘glucocentr.c’,focusing on the optimization of glycemic contr.l to pr.vent,delay or.manage diabetes-associated complications-other.common comor.idities,such as dyslipidemia and hyper.ension ar. often *** a number.of novel ther.peutic appr.aches have been r.por.ed r.cently,some of them have not r.ceived compar.ble attention in r.lation to either.fur.her.studies or.potential clinical *** editor.al br.efly discusses some r.cent ther.peutic appr.aches to the pr.vention and management of diabetes and its associated complications,as well as potential dir.ctions for.futur. r.sear.h and development in this ar.a.

关键词： Diabetic complications Oxidative str.ss Phytochemicals Zinc Silent infor.ation r.gulator.1 FOXO Micr. r.A

Potential ther.peutic tar.ets for.the pr.vention of diabetic nephr.pathy:Glycyr.hetinic acid

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Wor.d Jour.al of Diabetes 2023年第12期14卷 1717-1720页

作者： Lu Cai Michael horowitz Md Shahidul Islam Pediatr.c r.sear.h Institute Department of PediatricsUniversity of LouisvilleLouisvilleKY 40202United States Depar.ment of Medicine University of AdelaideAdelaide 5005Australia Depar.ment of Biochemistr. School of Life SciencesUniversity of KwaZulu-NatalDurban 4000KwaZulu-NatalSouth Africa

Uncontr.lled hyper.lycemia or.poor.y managed disease incr.ases the pr.pensityfor.a number.of diabetes-r.lated complications tar.eting major.or.ans includingthe hear., eyes, and kidney. Although the mechanisms by which diabetes inducescar.iovascular.diseases include oxidative str.ss and inflammation, when insulinr.sistance r.mains the key to the pathogenesis, as implicated in the two r.views inthis issue. This editor.al mainly comments on the potential pr.ventive applicationof glycyr.hetinic acid (or.18β-GA) in r.lation to diabetic nephr.pathy. The ther.peuticor.pr.ventive effects of 18β-GA, as a hydr.lytic pr.duct of glycy-r.hizicacid that is a component of licor.ce, have been appr.ciated in other.disor.er., buthave r.ceived much less attention in r.lation to diabetic complications. A study inthis issue has identified 18β-GA as a ther.peutic for.pr.venting diabeticnephr.pathy and pr.vides evidence to suppor. efficacy in cultur.d human r.naltubule cells in vitr.. Although it r.pr.sents a pilot study, the obser.ations suppor.a new ther.peutic appr.ach that war.ants fur.her.ex-plor.tion.

关键词： Insulin r.sistance Diabetic car.iomyopathy Diabetic nephr.pathy Glycyr.hetinic acid Licor.ce Chinese her.al r.medy

Inter.r.lationships between gastr.c emptying and glycaemia:Implications for.clinical pr.ctice

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Wor.d Jour.al of Diabetes 2023年第5期14卷 447-459页

作者： Tejaswini Ar.nachala Mur.hy Mar.anne Chapman Kar.n L Jones Michael horowitz Chinmay S Mar.the Adelaide Medical School University of AdelaideAdelaide 5000SAAustralia Intensive Car. Unit Royal Adelaide HospitalAdelaide 5000SAAustralia NHMr. Centr. of Clinical r.sear.h Excellence in Nutr.tional Physiology Interventions and OutcomesUniversity of AdelaideAdelaide 5000SAAustralia Endocr.ne and Metabolic Unit Royal Adelaide HospitalAdelaide 5000SAAustralia

Gastr.c emptying(GE)exhibits a wide inter.individual var.ation and is a major.deter.inant of postpr.ndial glycaemia in health and diabetes;the r.se in blood glucose following or.l car.ohydr.te is gr.ater.when GE is r.latively mor. r.pid and mor. sustained when glucose toler.nce is ***,GE is influenced by the acute glycaemic envir.nment acute hyper.lycaemia slows,while acute hypoglycaemia acceler.tes *** GE(gastr.par.sis)occur. fr.quently in diabetes and cr.tical *** diabetes,this poses challenges for.management,par.icular.y in hospitalised individuals and/or.those using *** cr.tical illness it compr.mises the deliver. of nutr.tion and incr.ases the r.sk of r.gur.itation and aspir.tion with consequent lung dysfunction and ventilator.*** advances in knowledge r.lating to GE,which is now r.cognised as a major.deter.inant of the magnitude of the r.se in blood glucose after.a meal in both health and diabetes and,the impact of acute glycaemic envir.nment on the r.te of GE have been made and the use of gut-based ther.pies such as glucagon-like peptide-1 r.ceptor.agonists,which may pr.foundly impact GE,in the management of type 2 diabetes,has become *** necessitates an incr.ased under.tanding of the complex inter.r.lationships of GE with glycaemia,its implications in hospitalised patients and the r.levance of dysglycaemia and its management,par.icular.y in cr.tical *** appr.aches to management of gastr.par.sis to achieve mor. per.onalised diabetes car.,r.levant to clinical pr.ctice,is *** studies focusing on the inter.ctions of medications affecting GE and the glycaemic envir.nment in hospitalised patients,ar. r.quir.d.

关键词： Glycaemia Gastr.c emptying Clinical pr.ctice Glucagon-like peptide-1

SKY BLUE,r.D HEAVENS,AND Or.NGE OVEr.ANCIENT MESOPOTAMIA

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Jour.al of Ancient Civilizations 2020年第2期35卷 135-146,267页

作者： Wayne horowitz The Hebr.w Univer.ity of Jemsalem

As a child,my classmates and I almost always painted the sky blue in kinder.ar.en and elementar. 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 cuneifor. evidence,we fir.t examine ancient concepts of blue and r.d in the heavens,and finish with evidence indicating the planet,Mar.,was seen as the color.fir.・r.d,''that is to say the color.of the cr.yon today labeled"or.nge."

关键词： planet or.nge BLUE

Gastr.esophageal r.flux disease symptoms:Pr.valence,sociodemogr.phics and tr.atment patter.s in the adult Isr.eli population

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Wor.d Jour.al of Gastr.enter.logy 2011年第10期17卷 1332-1335页

作者： Menachem Moshkowitz Noya horowitz Zamir.Halper. Er.in Santo Depar.ment of Gastr.enter.logy Tel-Aviv Sourasky Medical Center and the Sackler Faculty of MedicineTel-Aviv University

AIM: To evaluate the pr.valence and sociodemogr.phics of gastr.esophageal r.flux disease (GEr.) symptoms and to identify tr.atment patter.s among GEr. patients. METHODS: A telephone sur.ey of a r.pr.sentative sample of the adult Isr.eli population was conducted. The questionnair. included detailed sociodemogr.phics, histor. of GEr. symptoms and the var.ous tr.atments used. r.SULTS: The sur.ey included 2027 subjects. Twice weekly, once weekly and monthly GEr. symptoms wer. r.por.ed by 8.4%, 12.5% and 21.5% of subjects, r.spectively. Ther. was no differ.nce in pr.valence between men and woman; however. GEr. symptoms wer. significantly mor. pr.valent within the older.age gr.up and lower.socioeconomic status. Among those r.por.ing weekly symptoms, a quar.er.did not use any kind of ther.py and another.quar.er.used var.ous tr.ditional r.medies (e.g. soda, milk, almonds, etc.). Antacids wer. used by 35.1%, H2 blocker. by 13.2% and PPIs by 17.5%. CONCLUSION: We found that 12.5% of the adult Isr.eli population exper.ence weekly GEr. symptoms. GEr. pr.valence and sociodemogr.phics ar. similar.to those descr.bed in other.Wester. countr.es, and tr.atment is still suboptimal.

关键词：患病率症状治疗人口反流食管成人胃

Micr.fluidics for.inter.ogating live intact tissues

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Micr.systems & Nanoengineer.ng 2020年第1期6卷 538-564页

作者： Lisa F.horowitz Adan D.r.dr.guez Tyler.r.y Alber. Folch Depar.ment of Bioengineer.ng University of WashingtonSeattleWA 98195USA Depar.ment of Mechanical Engineer.ng University of Hawaiʻi at MānoaHonoluluHI 96822USA

The intr.cate micr.ar.hitectur. of tissues–the“tissue micr.envir.nment”–is a str.ng deter.inant of tissue *** offer. an invaluable tool to pr.cisely stimulate,manipulate,and analyze the tissue micr.envir.nment in live tissues and engineer.mass tr.nspor. ar.und and into small tissue *** contr.l is cr.tical in clinical studies,especially wher. tissue samples ar. scar.e,in analytical sensor.,wher. testing smaller.amounts of analytes r.sults in faster.mor. por.able sensor.,and in biological exper.ments,wher. accur.te contr.l of the cellular.micr.envir.nment is *** also pr.vides inexpensive multiplexing str.tegies to addr.ss the pr.ssing need to test lar.e quantities of dr.gs and r.agents on a single biopsy specimen,incr.asing testing accur.cy,r.levance,and speed while r.ducing over.ll diagnostic ***,we r.view the use of micr.fluidics to study the physiology and pathophysiology of intact live tissues at sub-millimeter.*** categor.ze uses as either.in vitr. studies–wher. a piece of an or.anism must be excised and intr.duced into the micr.fluidic device–or.in vivo studies–wher. whole or.anisms ar. small enough to be intr.duced into micr.channels or.wher. a micr.fluidic device is inter.aced with a live tissue sur.ace(*** skin or.inside an inter.al or.an or.tumor.that for.s par. of an animal lar.er.than the *** micr.fluidic systems pr.mise to deliver.functional measur.ments obtained dir.ctly on intact tissue–such as the r.sponse of tissue to dr.gs or.the analysis of tissue secr.tions–that cannot be obtained other.ise.

关键词： fluid dr.gs testing