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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

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Effects of Huluan decotion (护卵汤) on cyclophosphamide-induced autoimmune premature ovarian failure in Murine Models

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Journal of Traditional Chinese Medicine 2024年

作者： FENG Guiling ZHOU Xiaolin SHEN Chengwan LI Panxiao ABULIZI ·Abudula College of Medicial Science， Ningde Normal University Fujian Key Laboratory of toxicology and pharmacotoxicology Nanyang Medical College department of Intensive Care， Ningde Normal College Affiliated Ningde Hospital

Objectives: To investigate the therapeutic effect of Huluan decotion (护卵汤， HLD) on cyclophosphamide-induced premature ovarian failure (POF) in mice and its regulatory mechanisms. Methods: Female BALB/c mice were administered cyclophosphamide and administered received different doses of HLD for 28 d. Levels of sex hormone， such as estradiol (E2)， follicle stimulating hormone (FSH) and luteinizing hormone (LH) in the sera， were assessed using enzyme-linked immunosorbent assay (ELISA). Follicular structure variances were observed through hematoxylin and eosin (HE) staining， while Forkhead box L2 (FOXL2) expression were analyzed via immunohistochemical staining. The primary mechanism of POF were investigated through Western blot ***: E2 levels decreased， and FSH and LH levels increased in POF model mice， but these trends were reversed with HLD or premarin administration， the expressions of WNT family member 4 (Wnt4)， β-Catenin and FOXL2 were downregulated in POF model mice， whereas high expression levels were observed in control mice and other ***: HLD effectively treats POF induced with cyclophosphamide in mice by enhancing expressions of Wnt4， β-Catenin and FOXL2.

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A positive feedback inhibition of isocitrate dehydrogenase 3β on paired-box gene 6 promotes Alzheimer-like pathology

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2324-2340页

作者： Xin Wang Qian Liu Hai-tao Yu Jia-zhao Xie Jun-ning Zhao Zhi-ting Fang Min Qu Yao Zhang Ying Yang Jian-Zhi Wang department of Pathophysiology School of Basic MedicineKey Laboratory of Education Ministry of China/Hubei Province for Neurological DisordersTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina department of Fundamental Medicine Wuxi School of MedicineJiangnan UniversityWuxiJiangsu 214122China Hubei Provincial Key Laboratory for Applied toxicology Hubei Provincial Center for Disease Control and PreventionHubei Provincial Academy of Preventive MedicineWuhan 430000China Endocrine department of Liyuan Hospital Key Laboratory of Ministry of Education of China for Neurological DisordersTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430077China Co-innovation Center of Neuroregeneration Nantong UniversityNantong 226000China

Impaired brain glucose metabolism is an early indicator of Alzheimer’s disease(AD);however,the fundamental mechanism is *** this study,we found a substantial decline in isocitrate dehydrogenase 3β(IDH3β)levels,a critical tricarboxylic acid cycle enzyme,in AD patients and AD-transgenic mice’s *** investigations demonstrated that the knockdown of IDH3βinduced oxidation-phosphorylation uncoupling,leading to reduced energy metabolism and lactate *** resulting increased lactate,a source of lactyl,was found to promote histone lactylation,thereby enhancing the expression of paired-box gene 6(PAX6).As an inhibitory transcription factor of IDH3β,the elevated PAX6 in turn inhibited the expression of IDH3β,leading to tau hyperphosphorylation,synapse impairment,and learning and memory deficits resembling those seen in *** AD-transgenic mice,upregulating IDH3βand downregulating PAX6 were found to improve cognitive functioning and reverse AD-like ***,our data suggest that impaired oxidative phosphorylation accelerates AD progression via a positive feedback inhibition loop of IDH3β-lactate-PAX6-IDH3β.Breaking this loop by upregulating IDH3βor downregulating PAX6 attenuates AD neurodegeneration and cognitive impairments.

关键词： metabolism Alzheimer impaired

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High-throughput screening of novel TFEB agonists in protecting against acetaminopheninduced liver injury in mice

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Acta pharmaceutica Sinica B 2024年第1期14卷 190-206页

作者： Xiaojuan Chao Mengwei Niu Shaogui Wang Xiaowen Ma Xiao Yang Hua Sun Xujia Hu Hua Wang Li Zhang Ruili Huang Menghang Xia Andrea Ballabio Hartmut Jaeschke Hong-Min Ni Wen-Xing Ding department of pharmacology Toxicology and TherapeuticsUniversity of Kansas Medical CenterKansas CityKS 66160USA NMPA Key Laboratory for Research and Evaluation of Drug Metabolism&Guangdong Provincial Key Laboratory of New Drug Screening School of Pharmaceutical SciencesSouthern Medical UniversityGuangzhou 510515China department of Oncology the First Affiliated Hospital of Anhui Medical UniversityAnhui Medical UniversityHefei 230032China National Center for Advancing Translational Sciences National Institutes of HealthBethesdaMD 20892USA Telethon Institute of Genetics and Medicine TIGEMPozzuoliNaples 80131Italy Medical Genetics Department of Translational MedicineFederico II UniversityNaples 80131Italy department of Molecular and Human Genetics Baylor College of MedicineHoustonTX 77030USA department of Internal Medicine Division of GastroenterologyHepatology&MotilityUniversity of Kansas Medical CenterKansas CityKS 66160USA

Macroautophagy(referred to as autophagy hereafter)is a major intracellular lysosomal degradation pathway that is responsible for the degradation of misfolded/damaged proteins and *** studies showed that autophagy protects against acetaminophen(APAP)-induced injury(AILI)via selective removal of damaged mitochondria and APAP protein *** lysosome is a critical organelle sitting at the end stage of autophagy for autophagic degradation via fusion with *** the present study,we showed that transcription factor EB(TFEB),a master transcription factor for lysosomal biogenesis,was impaired by APAP resulting in decreased lysosomal biogenesis in mouse *** loss-of and gain-of function of hepatic TFEB exacerbated or protected against AILI,***,overexpression of TFEB increased clearance of APAP protein adducts and mitochondria biogenesis as well as SQSTM1/p62-dependent non-canonical nuclear factor erythroid 2-related factor 2(NRF2)activation to protect against *** also performed an unbiased cell-based imaging high-throughput chemical screening on TFEB and identified a group of TFEB *** these agonists,salinomycin,an anticoccidial and antibacterial agent,activated TFEB and protected against AILI in *** conclusion,genetic and pharmacological activating TFEB may be a promising approach for protecting against AILI.

关键词： Autophagy DILI Drug screening Hepatotoxicity Lysosome Mitochondria Mitophagy NRF2

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Role of polyphenols in epilepsy: from the perspective of gut microbiota

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Food Science and Human Wellness 2024年

作者： Xiaoxue Xu Jian Shi Yinsi Tang Guiyang Cai Chao Ma Wuyang Wang Rui Feng Tomasz Boczek Zhenwei He Feng Guo department of pharmaceutical toxicology， School of pharmacy， China Medical University Shenyang department of Neurology， the First Hospital of China Medical University department of pharmacy， the Fourth Affiliated Hospital of China Medical University department of Gastroenterology， the Fourth Affiliated Hospital of China Medical University department of Obstetrics and Gynecology， Shengjing Hospital of China Medical University Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education， School of pharmaceutical Engineering， Shenyang pharmaceutical University Jiangsu Province Key Laboratory of Anesthesiology， Xuzhou Medical University department of Molecular Neurochemistry， Medical University of Lodz department of Neurology， the Fourth Affiliated Hospital of China Medical University

Epilepsy is a devastating neurological condition that affects over 70 million people worldwide. Apart from idiopathic epilepsy， numerous diseases have been reported to cause secondary epilepsy. Polyphenols， ubiquitously existing in fruits and vegetables， has become a promising neuroprotective candidate against multiple neurological abnormalities due to its interplay with gut microbiome composed of the bacterial population in gastrointestinal system. This bioactive compound is also being tested for the management of epileptogenesis. However， there is still insufficient evidence from mechanistic studies to demonstrate the causal relationship between anti-epileptic effect of polyphenols and microbial alteration. In this review， we provide the brief overview of epilepsy， polyphenols and gut microbiota. We then analysis the association of polyphenols and gut microbiota particularly in the epilepsy and symptomatic seizures-induced by epilepsy-related disorders. We also discuss the possibility for the combined application with probiotics to improve the bioavailability and bioaccessibility of polyphenols for expanding its anti-epileptic function. We finally summarize the therapeutic potential of anti-seizure polyphenols through affecting gut microbiome， and propose that the anti-epileptic effect of polyphenols may be tightly relevant to intestinal bacterial flora for overcoming epilepsy and its comorbidities simultaneously. Therefore， the dietary polyphenols targeting specific bacteria may achieve the outcome of ‘one stone， two birds’.

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Biological,pathological,and multifaceted therapeutic functions of exosomes to target cancer

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Oncology Research 2024年第1期32卷 73-94页

作者： VIGNESH BALAJI E DIVYA RAMESH MANISHA CHUNGAN SHAJU AKSHARA KUMAR SAMYAK PANDEY RAKSHA NAYAK V.ALKA SRISHTI MUNJAL AMIR SALIMI K.SREEDHARA RANGANATH PAI SHANKAR M.BAKKANNAVAR department of pharmacology Manipal College of Pharmaceutical SciencesManipal Academy of Higher EducationManipalKarnataka576104India department of Forensic Medicine and toxicology Kasturba Medical CollegeManipal Academy of Higher EducationManipalKarnataka576104India School of Health and Community Services Durham CollegeOshawaOntarioL1G2G5Canada department of pharmaceutical Regulatory Affairs and Management Manipal College of Pharmaceutical SciencesManipal Academy of Higher EducationManipalKarnataka576104India department of Clinical Psychology Manipal College of Health ProfessionsManipal Academy of Higher EducationManipalKarnataka576104India department of Speech and Hearing Manipal College of Health ProfessionsManipal Academy of Higher EducationManipalKarnataka576104India department of pharmacy Practice Manipal College of Pharmaceutical SciencesManipal Academy of Higher EducationManipalKarnataka576104India

Exosomes,small tiny vesicle contains a large number of intracellular particles that employ to cause various diseases and prevent several pathological events as well in the human *** is considered a“double-edged sword”,and depending on its biological source,the action of exosomes varies under physiological ***,the isolation and characterization of the exosomes should be performed accurately and the methodology also will vary depending on the exosome ***,the uptake of exosomes from the recipients’cells is a vital and initial step for all the physiological *** are different mechanisms present in the exosomes’cellular uptake to deliver their cargo to acceptor *** the exosomal uptake takes place,it releases the intracellular particles that leads to activate the physiological *** though exosomes have lavish functions,there are some challenges associated with every step of their preparation to bring potential therapeutic ***,overcoming the pitfalls would give a desired quantity of exosomes with high purity.

关键词： Exosomes Physiology Cancer Therapeutics Challenges

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Heavy Metal Levels and Ecological Risk in Crude Oil-Contaminated Soils from Okpare-Olomu, Niger Delta, Nigeria

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Journal of Environmental Protection 2024年第4期15卷 415-438页

作者： Adedoyin Olubunmi Bankole Akinyemi Olufemi Ogunkeyede Harrison Agboro Prince Alex Ekhorutomwen Osasenaga Israel Otuomagie Khadijah Ateda Isimekhai Ekaette Akpan Fadairo Efe Jeffery Isukuru department of Environmental Management and toxicology College of Science Federal University of Petroleum Resources Effurun Nigeria department of Biology and Environmental Science College of Arts and Sciences University of New Haven West Haven USA department of Chemistry University of Abuja Abuja Nigeria department of Science Laboratory Technology Petroleum Training Institute Effurun Nigeria

Crude oil spills have inflicted extensive disruption upon the Niger Delta ecosystem, resulting in crop loss and severe environmental damage. Such spills exacerbate heavy metal concentration within soil due to the presence of metallic ions. The Okpare-Olomu community has borne the brunt of crude oil pollution from illicit bunkering, sabotage, and equipment malfunction. This study targets an evaluation of ecological hazards linked to heavy metals (HMs) in crude oil impacted agriculturally soils within Okpare-Olomu in Ughelli South LGA of Delta State. In this study, 24 topsoil samples were obtained from areas affected by crude oil pollution;the heavy metal content was evaluated through atomic absorption spectrometry. The concentration ranges for HMs (mg/kg) in soil were: 24.1 - 23,174 (Cu);0.54 - 37.1 (Cd);9.05 - 54 (Cr);12 - 174 (Ni);18.5 - 8611 (Pb);and 148 - 9078 (Zn) at a soil depth of 0 - 15 cm. Notably, metal concentrations were recorded to be above permissible World Health Organization limits. Predominantly, Zn and Pb recorded higher heavy metal concentration when compared to other heavy metals analysed, notably at sampling points PT7 through PT24. Zinc and Pb contamination exhibited highly significant contamination factors, and contamination severity was evidenced across all sample points, signifying a grave risk level. Pollution load indices indicated pervasive extreme pollution levels. Geoaccumulation indices signaled moderate to strong pollution, mainly by Pb and Zn. Ecological risk assessments revealed variable levels of heavy metal contamination, from low to very high, with potential ecological risk reflecting markedly elevated levels. This study underscores the imperative for soil remediation to rectify ecological imbalances in agriculturally affected soil constituents.

关键词： Heavy Metals Crude Oil Pollution Degree of Contamination Potential Risk Index

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Zinc finger protein 831 promotes apoptosis and enhances chemosensitivity in breast cancer by acting as a novel transcriptional repressor targeting the STAT3/Bcl2 signaling pathway

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Genes & Diseases 2024年第1期11卷 430-448页

作者： Jun Fan Zhe Zhang Hongqiang Chen Dongjiao Chen Wenbo Yuan Jingzhi Li Yong Zeng Shimeng Zhou Shu Zhang Gang Zhang Jiashen Xiong Lu Zhou Jing Xu Wenbin Liu Yan Xu department of Breast and Thyroid Surgery Daping HospitalArmy Medical University(Third Military Medical University)Chongqing 400042China Institute of toxicology College of Preventive MedicineArmy Medical University(Third Military Medical University)Chongqing 400038China department of Environmental Health College of Preventive MedicineArmy Medical University(Third Military Medical University)Chongqing 400038China Anesthesia and Intensive Care Chinese University of Hong KongHong Kong SAR 999077China School of Public Health Xinxiang Medical UniversityXinxiangHenan 453003China School of Public Health China Medical UniversityShenyangLiaoning 110122China

Emerging evidence suggested that zinc finger protein 831(ZNF831)was associated with immune activity and stem cell regulation in breast ***,the roles and molec-ular mechanisms of ZNF831 in oncogenesis remain ***831 expression was significantly diminished in breast cancer which was associated with promoter CpG methylation but not *** over-expression of ZNF831 suppressed breast cancer cell proliferation and col-ony formation and promoted apoptosis in vitro,while knockdown of ZNF831 resulted in an opposite ***-proliferation effect of ZNF831 was verified in *** analysis of public databases and transcriptome sequencing both showed that ZNF831 could enhance apoptosis through transcriptional regulation of the JAK/STAT *** and luciferase report assays demonstrated that ZNF831 could directly bind to one specific region of STAT3 promoter and induce the transcriptional inhibition of *** a result,the attenuation of STAT3 led to a restraint of the transcription of Bcl2 and thus accelerated the apoptotic *** of STAT3 diminished the apoptosis-promoting effect of ZNF831 in breast cancer cell ***,ZNF831 could ameliorate the anti-proliferation effect of capecitabine and gemcitabine in breast cancer cell *** findings demonstrate for the first time that ZNF831 is a novel transcriptional suppressor through inhibiting the expression of STAT3/Bcl2 and promoting the apoptosis process in breast cancer,suggesting ZNF831 as a novel biomarker and potential therapeutic target for breast cancer patients.

关键词： Apoptosis Breast cancer Chemosensitivity STAT3 ZNF831

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Evidence-based expert consensus on clinical management of safety of Bruton’s tyrosine kinase inhibitors(2024)

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Chinese Journal of Cancer Research 2024年第3期36卷 240-256页

作者： Zaiwei Song Dan Jiang Lingling Yu Yixuan Chen Daobin Zhou Yue Li Depei Wu Lingli Zhang Liyan Miao Jun Ma Jun Zhu Hongmei Jing Rongsheng Zhao the Steering Committee,the Consensus Panel and the Evidence Synthesis Group Evidence-based pharmacy Professional Committee of Chinese pharmaceutical Association(CPA) Hospital pharmacy Professional Committee of Chinese pharmaceutical Association(CPA) Division of Therapeutic Drug Monitoring of Chinese pharmacological Society(CPS) Expert Committee on Lymphoma of Chinese Society of Clinical Oncology(CSCO) Expert Committee on Leukemia of Chinese Society of Clinical Oncology(CSCO) Society of Integrative Cardio-Oncology of China Anti-Cancer Association(CACA) Chinese Society of Hematology of Chinese Medical Association(CMA) Hospital pharmacy Professional Committee of Cross-Straits Medicine Exchange Association(SMEA) department of pharmacy Peking University Third HospitalBeijing 100191China Institute for Drug Evaluation Peking University Health Science CenterBeijing 100191China Therapeutic Drug Monitoring and Clinical toxicology Center Peking UniversityBeijing 100191China department of pharmacy Administration and Clinical pharmacy School of Pharmaceutical SciencesPeking UniversityBeijing 100191China department of Hematology Peking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100005China department of Cardiology the First Affiliated HospitalHarbin Medical UniversityHarbin 150001China department of Hematology the First Affiliated Hospital of Soochow UniversitySuzhou 215006China department of pharmacy Evidence-based Pharmacy CenterWest China Second HospitalSichuan UniversityChengdu 610041China department of pharmacy the First Affiliated Hospital of Soochow UniversitySuzhou 215006China department of Hematology and Oncology Harbin Institute of Hematology and OncologyHarbin 150010China Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Department of LymphomaPeking University Cancer Hospital&InstituteBeijing 100142China department of Hematology Peking University Third HospitalBeijing 100191China 不详

Bruton’s tyrosine kinase inhibitors(BTKis)have revolutionized the treatment of B-cell ***,safety issues related to the use of BTKis may hinder treatment continuity and further affect clinical efficacy.A comprehensive and systematic expert consensus from a pharmacological perspective is lacking for safety issues associated with BTKi treatment.A multidisciplinary consensus working group was established,comprising 35 members from the fields of hematology,cardiovascular disease,cardio-oncology,clinical pharmacy,and evidencebased *** evidence-based expert consensus was formulated using an evidence-based approach and the Delphi *** Joanna Briggs Institute Critical Appraisal(JBI)tool and Grading of Recommendations Assessment,Development,and Evaluation(GRADE)approach were used to rate the quality of evidence and grade the strength of recommendations,*** consensus provides practical recommendations for BTKis medication based on nine aspects within three domains,including the management of common adverse drug events such as bleeding,cardiovascular events,and hematological toxicity,as well as the management of drug-drug interactions and guidance for special *** multidisciplinary expert consensus could contribute to promoting a multi-dimensional,comprehensive and standardized management of BTKis.

关键词： Consensus BTK inhibitors safety adverse drug events drug-drug interactions

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Investigating the genetic diversity of several varieties of Iranian tomato (Solanum lycopersicum) using RAPD and ISSR molecular markers

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Food and Health 2024年第4期6卷 19-26页

作者： Bahareh Ahang Sanaz Pashapour Aida Ghasemi Abbas Zabihi department of Biology Faculty of Basic SciencesIslamic Azad UniversityRashtBranchRasht 0098813Iran department of pharmacology and toxicology Faculty of Pharmacy and Pharmaceutical SciencesIslamic Azad UniversityMedical Sciences BranchTehranIran School of Medicine Medical University of HamedanHamedanIran

Background:Numerous studies have demonstrated the existence of approximately 7,500 genetic tomato varieties ***,it is crucial to assess the genetic diversity among tomato *** study aimed to investigate the genetic diversity of selected Iranian tomato cultivars(Solanum lycopersicum)using RAPD and ISSR molecular ***:Ten RAPD primers and ten ISSR primers were employed to assess the genetic diversity among 10 tomato cultivars:Matin,RFT 112,Hirad,Golsar,Raha,Hengam,Hedah,Fasa,JS12,and *** analysis involved the UPGMA algorithm and NTYSYSpc ***:RAPD analysis revealed close genetic proximity between Fasa and JS12,as well as between Raha and ***,the RFT 112,Hengam,Hirad,and Emerald cultivars exhibited significant genetic diversity within this *** primer analysis identified Hengam as the most diverse variety,while Matin,Emerald,and Vibrid,as well as Raha and JS12,displayed genetic similarities with minimal observed ***,the overall analysis of the cultivars using RAPD and ISSR markers indicated that Hengam exhibited the highest diversity among all the ***,Raha and JS12 demonstrated limited diversity in this ***:This research demonstrates substantial genetic diversity among the investigated tomato varieties,with Hengam displaying the highest diversity within this ***,ISSR markers proved more effective in determining genetic diversity in tomato plants.

关键词： Solanum lycopersicum tomato genetic diversity RAPD ISSR

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