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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

Red honeybush(Cyclopia genistoides)tea mitigates oxidative imbalance and hyperlipidemia,while improving glucose homeostasis in type 2 diabetic rats

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Food Science and Human Wellness 2023年第6期12卷 2029-2039页

作者： Xin Xiao Ochuko L.Erukainure md.shahidul islam Department of Biochemistry University of KwaZulu-NatalWestville CampusDurban 4000South Africa Department of Pharmacology University of the Free StateBloemfontein 9300South Africa

Red honeybush tea(RHT)is a tea product developed from Cyclopia *** is endemic to South *** refreshment,RHT has over the years been used traditionally in the treatment of various diseases including type 2 *** study investigated the in vivo antioxidant and anti-diabetic activity of RHT concentrated hot water extract in type 2 diabetes(T2D)model of rats.T2D was induced starting with feeding 10%fructose solution ad libitum for 2 weeks followed by a single intraperitoneal injection of streptozotocin(40 mg/kg body weight(BW)).Five weeks of treatment of RHT led to significant(PmdA levels and enhanced level of GSH,activity of SOD,catalase,GR in most of organs(pancreas,liver,kidneys,and heart).Signifi cantly(P<0.05)improved morphological changes in the islets andβ-cells were observed in rats treated with *** data of this study suggest that RHT demonstrates an outstanding antioxidant and anti-diabetic effects in STZ-induced T2D model of rats.

关键词： Red honeybush tea(Cyclopia genistoides) Antioxidants Anti-diabetes Type 2 diabetes

Recent therapeutic targets for the prevention 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 Department of Biochemistry School of Life SciencesUniversity of KwaZulu-NatalDurban 4000KwaZulu-NatalSouth Africa Pediatric Research Institute University of LouisvilleLouisvilleKY 40202United States Department of Medicine University of AdelaideAdelaide 5005Australia

Diabetes and associated complications represent major global public health issues which are associated with impaired quality of life and premature *** some diabetic complications have decreased in the developed world,the majority are still prevalent,with an increasing trend in the developing *** used therapies are mainly‘glucocentric’,focusing on the optimization of glycemic control to prevent,delay or manage diabetes-associated complications-other common comorbidities,such as dyslipidemia and hypertension are often *** a number of novel therapeutic approaches have been reported recently,some of them have not received comparable attention in relation to either further studies or potential clinical *** editorial briefly discusses some recent therapeutic approaches to the prevention and management of diabetes and its associated complications,as well as potential directions for future research and development in this area.

关键词： Diabetic complications Oxidative stress Phytochemicals Zinc Silent information regulator 1 FOXO Micro RNA

Potential therapeutic targets for the prevention of diabetic nephropathy:Glycyrrhetinic acid

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World Journal of Diabetes 2023年第12期14卷 1717-1720页

作者： Lu Cai Michael Horowitz md shahidul islam Pediatric Research Institute Department of PediatricsUniversity of LouisvilleLouisvilleKY 40202United States Department of Medicine University of AdelaideAdelaide 5005Australia Department of Biochemistry School of Life SciencesUniversity of KwaZulu-NatalDurban 4000KwaZulu-NatalSouth Africa

Uncontrolled hyperglycemia or poorly managed disease increases the propensityfor a number of diabetes-related complications targeting major organs includingthe heart, eyes, and kidney. Although the mechanisms by which diabetes inducescardiovascular diseases include oxidative stress and inflammation, when insulinresistance remains the key to the pathogenesis, as implicated in the two reviews inthis issue. This editorial mainly comments on the potential preventive applicationof glycyrrhetinic acid (or 18β-GA) in relation to diabetic nephropathy. The therapeuticor preventive effects of 18β-GA, as a hydrolytic product of glycy-rrhizicacid that is a component of licorice, have been appreciated in other disorders, buthave received much less attention in relation to diabetic complications. A study inthis issue has identified 18β-GA as a therapeutic for preventing diabeticnephropathy and provides evidence to support efficacy in cultured human renaltubule cells in vitro. Although it represents a pilot study, the observations supporta new therapeutic approach that warrants further ex-ploration.

关键词： Insulin resistance Diabetic cardiomyopathy Diabetic nephropathy Glycyrrhetinic acid Licorice Chinese herbal remedy

Harpephyllum caffrum stimulates glucose uptake,abates redox imbalance and modulates purinergic and glucogenic enzyme activities in oxidative hepatic injury

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Asian Pacific Journal of Tropical Biomedicine 2022年第1期12卷 9-19页

作者： Kolawole A.Olofinsan Ochuko L.Erukainure Beseni K.Brian md.shahidul islam Department of Biochemistry School of Life SciencesUniversity of KwaZulu-Natal(Westville Campus)Durban 4000South Africa Department of Pharmacology University of the Free StateBloemfontein 9300South Africa

Objective:To investigate the antioxidative and antidiabetic effects of Harpephyllum caffrum bark infusion as well as its effects on glucogenic and nucleotide hydrolyzing enzyme activities in FeSO4-induced oxidative stress in rat hepatic ***:Harpephyllum caffrum infusion was prepared from dried plant materials(40 g)infused in boiling water(400 mL)for 20 min at room *** antioxidative and inhibitory activities against carbohydrate digestive enzymes of the infusion were determined using established *** liver tissues of rats were used for glucose uptake assay and to evaluate the infusion’s effect on endogenous antioxidant,glucogenic,and nucleotide hydrolyzing enzyme activities in FeSO4-induced hepatic ***:The Harpephyllum caffrum infusion significantly reduced ferric iron(FRAP)and free radicals(OH•and DPPH)in a dose-dependent *** inhibitedα-amylase andα-glucosidase activities and increased glucose uptake in hepatic ***4 significantly decreased glutathione concentration,catalase,and superoxide dismutase activities while increasing malondialdehyde level,glycogen phosphorylase,fructose-1,6-bisphosphatase,and adenosine triphosphatase ***,treatment with Harpephyllum caffrum infusion reversed FeSO4-induced *** of the infusion revealed the presence of catechol,O-pyrocatechuic acid,mequinol,maltol,and glycoside ***:The Harpephyllum caffrum infusion demonstrates antidiabetic and antioxidative potentials in in vitro models of type 2 diabetes as depicted by its ability to inhibit carbohydrate digestive enzymes,mitigate oxidative imbalance,and regulate glucogenic and nucleotide hydrolyzing enzyme activities in oxidative hepatic injury.

关键词： Harpephyllum caffrum Antioxidant Oxidative injury Carbohydrate dysmetabolism

Comparative effects of xylitol and erythritol on modulating blood glucose;inducing insulin secretion;reducing dyslipidemia and redox imbalance in a type 2 diabetes rat model

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Food Science and Human Wellness 2023年第6期12卷 2052-2060页

作者： Nontokozo Z.Msomi Ochuko L.Erukainure Veronica F.Salau Kolawole A.Olofinsan md.shahidul islam Department of Biochemistry University of KwaZulu-NatalWestville CampusDurban 4000South Africa Department of Pharmacology University of the Free StateBloemfontein 9300South Africa

Xylitol and erythritol have been reported in numerous previous and recent studies as potential antidiabetic sweeteners,however,it is not certain which one is most effective in this *** the present study,the effects of xylitol and erythritol were comparatively investigated on blood glucose,insulin level,dyslipidemia,pancreatic islet morphology andβ-cell function,and redox imbalance in a type 2 diabetes(T2D)model of ***-week-old male Sprague-Dawley rats were randomly divided into 8 groups:Normal Control(NC),Diabetic Control(DC),Diabetic Xylitol 5%(DX5),Diabetic Xylitol 10%(DX10),Diabetic Xylitol 20%(DX20),Diabetic Erythritol 5%(DE5),Diabetic Erythritol 10%(DE10),and Diabetic Erythritol 20%(DE20).T2D was induced in the diabetic groups initially by feeding 10%fructose solution to induce insulin resistance followed by an intraperitoneal injection of streptozotocin(40 mg/kg body weight)dissolved in citrate buffer(pH 4.5)to induce partial pancreaticβ-cells *** animals in NC group were fed with normal drinking water and injected with citrate buffer *** the confi rmation of diabetes,the xylitol and erythritol with above-mentioned concentrations were supplied to the respective animal groups when the animals in NC and DC groups were supplied with normal drinking *** 8 weeks intervention period,the body weight,fl uid and water intake,blood glucose,serum alanine aminotransferase,aspartate aminotransferase,CK-MB and creatinine were signifi cantly decreased,while the serum insulin level,serum lipids,glucose tolerance ability,pancreatic islet morphology andβ-cell function,pancreatic and serum redox imbalance were improved in the most xylitol and erythritol fed groups compared to the DC group,when effects were better for xylitol compared to *** data of this study suggests that xylitol has better antioxidant and antidiabetic effects compared to ***,xylitol can be used as a preferrable dietary anti-diabetic sweetener

关键词： Xylitol Erythritol Sweeteners Type 2 diabetes Oxidative stress

Senna petersiana inhibits key digestive enzymes and modulates dysfunctional enzyme activities in oxidative pancreatic injury

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Asian Pacific Journal of Tropical Biomedicine 2022年第7期12卷 300-311页

作者： Kolawole A.Olofinsan Ochuko L.Erukainure Nontokozo Z.Msomi md.shahidul islam Department of Biochemistry University of KwaZulu-NatalWestville CampusDurban 4000South Africa Department of Pharmacology University of the Free StateBloemfontein 9300South Africa

Objective:To evaluate the effect of Senna petersiana leaf extracts on key digestive enzymes and FeSO_(4)-induced oxidative ***:Dried Senna petersiana leaf powder(60 g)was defatted in n-hexane and then extracted sequentially at room temperature with dichloromethane,methanol,and distilled *** total phytochemical content of the extracts was estimated using established *** in vitro antioxidant,anti-lipase,and antidiabetic activities and the effect of the extracts on intestinal glucose absorption and FeSO_(4)-induced pancreatic oxidative injury were determined using different ***,GC-MS analysis was performed to identify the main compounds of the plant *** docking analysis was also carried out to evaluate the binding energy of compounds with digestive ***:Senna petersiana leaf extracts showed significant antioxidant activities in FRAP,DPPH,and hydroxyl radical scavenging *** also inhibited pancreatic lipase and lowered intestinal glucose absorption by suppressing activities ofα-amylase andα-*** with the extracts also lowered lipid peroxidation(malondialdehyde),nitric oxide level,acetylcholinesterase,and ATPase activities with simultaneous improvement of antioxidant(catalase,superoxide dismutase,glutathione)capacity in the type 2 diabetes model of oxidative pancreatic ***-MS characterization of the extracts revealed the presence of stilbenoids,alkaloids,and other *** docking screening assay indicated the extract phytochemicals showed strong interaction with the active site amino acids of the targeted digestive *** the Senna petersiana compounds,veratramine had the highest affinity forα-amylase and lipase,whereas dihydrostilbestrol was most attracted toα-***:Senna petersiana inhibits carbohydrate digestive enzymes,reduces intestinal glucose absorption,and exerts ameliorative effects on FeSO_(4)-induced oxidative pancreatic injury wi

关键词： Senna petersiana Antioxidant Digestive enzymes Oxidative pancreatic injury Type 2 diabetes

Rhus longipes (Engl.) infusions improve glucose metabolism and mitigate oxidative biomarkers in ferrous sulfate-induced renal injury

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Asian Pacific Journal of Tropical Biomedicine 2022年第11期12卷 453-465页

作者： Brian K.Beseni Kolawole AOlofinsan Veronica F.Salau Ochuko L.Erukainure md.shahidul islam Department of Biochemistry University of KwaZulu-NatalWestville CampusDurban 4000South Africa Department of Pharmacology University of the Free StateBloemfontein 9300South Africa

Objective:To explore the antioxidant and antidiabetic activities of Rhus longipes(***)leaf and stem bark aqueous ***:*** leaf and stem bark infusions were characterized via gas-chromatography mass-spectroscopy(GC-MS)*** vitro antioxidant and carbohydrate and lipid digestive enzyme inhibitory activities of *** infusions were ***,the modulatory effects of *** infusions on intestinal glucose absorption,muscle glucose uptake,and biomarkers of renal oxidative injury were *** docking was performed to determine the binding affinities of the identified compounds from the leaf and stem bark infusions on carbohydrate and lipid digestive ***:GC-MS analysis revealed the presence of several phytocompounds,including palmitoleic acid,octadecanamide,24,25-dihydroxyvitamin D and L-ascorbic *** bark infusion had significantly higher total phenolic contents compared with the leaf infusion,with better DPPH scavenging[IC_(50):(10.50±1.03)μg/mL]and ferric reducing[IC_(50):(9.85±0.32)μg/mL]activities(P<0.05).Both *** infusions at their highest concentrations significantly increased glucose uptake in yeast suspension and rat psoas muscle with marked suppression of glucose absorption in the rat jejunum(P<0.05).With no cytotoxicity on Vero cells,the infusions lowered lipid peroxidation,increased cellular reduced glutathione concentration,and the activities of superoxide dismutase and catalase in renal homogenate treated with FeSO_(4).Conclusions:*** shows antioxidant and antidiabetic activities and could be a potential therapeutic candidate for diabetes.

关键词： Antioxidant Oxidative biomarkers Enzyme inhibition Antidiabetic Rhus longipes Searsia longipes

Vaccine efficacy and SARS-CoV-2 control in California and *** the session 2020e2026:A modeling study

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Infectious Disease Modelling 2022年第1期7卷 62-81页

作者： md Shahriar Mahmud md Kamrujjaman md Mashih Ibn Yasin Adan md Alamgir Hossain md Mizanur Rahman md shahidul islam Muhammad Mohebujjaman md Mamun Molla Department of Computer Science and Engineering State University of BangladeshDhaka1205Bangladesh Department of Mathematics University of DhakaDhaka1000Bangladesh Department of Mathematics and Statistics University of CalgaryCalgaryABCanada Computational Biology Research Lab(CBRL) Department of PharmacyJagannath UniversityDhaka1100Bangladesh Hitotsubashi Institute for Advanced Study Hitotsubashi UniversityNaka KunitachiTokyo186-8601Japan Department of Mathematics and Physics Texas A&M International UniversityLaredoTX78041USA Department of Mathematics&Physics North South UniversityDhaka1229Bangladesh Center for Applied Scientific Computing(CASC) North South UniversityDhaka1229Bangladesh

Background:Besides maintaining health precautions,vaccination has been the only prevention from SARS-CoV-2,though no clinically proved 100%effective vaccine has been developed till *** this stage,to withhold the debris of this pandemic-experts need to know the impact of the vaccine efficacy rates,the threshold level of vaccine effectiveness and how long this pandemic may extent with vaccines that have different efficacy *** this article,a mathematical model study has been done on the importance of vaccination and vaccine efficiency rate during an ongoing ***:We simulated a five compartment mathematical model to analyze the pandemic scenario in both California,and whole *** considered four vaccines,Pfizer(95%),Moderna(94%),AstraZeneca(79%),and Johnson&Johnson(72%),which are being used rigorously to control the SARS-CoV-2 pandemic,in addition with two special cases:a vaccine with 100%efficacy rate and no vaccine under ***-CoV-2 related data of California,and *** used in this ***:Both the infection and death rates are very high in *** model suggests that the pandemic situation in California will be under control in the last quartile of the year 2023 if vaccination program is continued with the Pfizer *** this time,six waves may happen from the beginning of the immunization where the case fatality and recovery rates will be 1.697%and 98.30%,***,according to the considered model,this period might be extended to the mid of 2024 when vaccines with lower efficacy rates are *** the other hand,the daily cases and deaths in the *** be under control at the end of 2026 with multiple *** the number of susceptible people will fall down to none in the beginning of 2027,there is less chance to stop the vaccination program if vaccinated with a vaccine other than a 100%effective vaccine or Pfizer,and at that case vaccination program must run till the mid of *** to this s

关键词： Vaccine Model California Control measurement SARS-CoV-2