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Autophagy and mitophagy as potential therapeutic targets in diabetic heart condition:Harnessing the power of nanotheranostics

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Asian Journal of Pharmaceutical Sciences 2024年第3期19卷 79-101页

作者： Sagnik Nag Oishi Mitra Bhanu Maturi Simran Preet Kaur Ankita Saini Muskan Nama Soumik Roy Souvik Samanta Leena Chacko Rohan Dutta Suresh Babu Sayana Vetriselvan Subramaniyan Jasvinder Singh Bhatti Ramesh Kandimalla Jeffrey Cheah School of Medicine and Health Sciences Monash University MalaysiaJalan Lagoon Selatan47500 Bandar SunwaySelangorMalaysia department of Bio-Sciences School of Bio-Sciences&Technology(SBST)Vellore Institute of Technology(VIT)Tiruvalam RoadVellore 632014Tamil NaduIndia department of Internal Medicine University of Alabama at BirminghamBirminghamALUSA department of Microbiology University of Delhi(South Campus)Benito Juarez RoadNew Delhi 110021India department of Biotechnology Indian Institute of TechnologyHyderabad(IIT-H)SangareddyTelangana 502284India BioAnalytical Lab Meso Scale Discovery1601 Research BlvdRockvilleMDUSA department of pharmacology Government Medical CollegeSuryapetTelanganaIndia Laboratory of Translational Medicine and Nanotherapeutics Department of Human Genetics and Molecular MedicineSchool of Health SciencesCentral University of PunjabBathindaIndia department of Biochemistry Kakatiya Medical CollegeWarangal 506007India

Autophagy and mitophagy pose unresolved challenges in understanding the pathology of diabetic heart condition(DHC),which encompasses a complex range of cardiovascular issues linked to diabetes and associated *** significant progress in reducing mortality rates from cardiovascular diseases(CVDs),heart failure remains a major cause of increased morbidity among diabetic *** cellular processes are essential for maintaining cellular balance and removing damaged or dysfunctional components,and their involvement in the development of diabetic heart disease makes them attractive targets for diagnosis and *** a variety of conventional diagnostic and therapeutic strategies are available,DHC continues to present a significant ***-of-care diagnostics,supported by nanobiosensing techniques,offer a promising alternative for these complex *** conventional medications have been widely used in DHC patients,they raise several concerns regarding various physiological *** medicine places great emphasis on the application of nanotechnology to target autophagy and mitophagy in DHC,offering a promising approach to deliver drugs beyond the limitations of traditional *** article aims to explore the potential connections between autophagy,mitophagy and DHC,while also discussing the promise of nanotechnology-based theranostic interventions that specifically target these molecular pathways.

关键词： Autophagy Diabetes Diabetic heart condition Mitophagy Nanotheranostics Nanomedicine

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N-acetylcysteine and zinc sulphate abate di-2-ethylhexyl phthalate-mediated reproductive dysfunction in rats:Focus on oxidative and sex hormone receptors mechanisms

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Asian pacific Journal of Reproduction 2024年第5期13卷 228-240页

作者： Victor Oghenekparobo Emojevwe Mega Obukohwo Oyovwi Kayode Ezekiel Adewole Peggy Ejiro Ohwin Adeniran Oluwadamilare Akinola Alexander Obidike Naiho Eze Kingsley Nwangwa Victor Omo-Idonije Motunrayo Lade-Ige Benneth Ben-Azu department of Physiology University of Medical SciencesOndo CityOndo StateNigeria department of Physiology Delta State UniversityAbrakaDelta StateNigeria department of Physiology Adeleke UniversityEdeOsun StateNigeria department of Biochemistry University of Medical SciencesOndo CityOndo StateNigeria department of pharmacology Delta State UniversityAbrakaDelta StateNigeria

Objective:To investigate the potential of N-acetylcysteine(NAC)and zinc sulphate(ZnSO_(4))in mitigating reproductive dysfunction caused by di-2-ethylhexyl phthalate(DEHP)in rats and to understand the underlying mechanisms,specifically oxidative stress and sex hormone receptor ***:Thirty-five male Wistar rats were randomly divided into five equal groups(n=7 per group).Group 1 was administered 0.5 mL of distilled water and served as the control *** 2 was given only DEHP(750 mg/kg/day),while group 3,4 and 5 were given DEHP(750 mg/kg/day)plus NAC(100 mg/kg/day),DEHP(750 mg/kg/day)plus ZnSO_(4)(0.5 mg/kg/day),and DEHP(750 mg/kg/day)plus NAC(100 mg/kg/day)as well as ZnSO_(4)(0.5 mg/kg/day),*** treatments lasted for 21 *** were obtained after the rats were sacrificed,and hormones levels in the serum and markers of oxidative stress in the testicles were analyzed using the enzyme-linked immunosorbent *** amount of androgen receptors in the testicles was determined by immunohistochemistry,and the susceptibility of testosterone and DEHP to bind to androgen receptor and 5α-reductase was determined by molecular docking ***:DEHP decreased reproductive hormones,testicular antioxidant enzymes,increased malondialdehyde levels,and negatively impacted histology of the pituitary and *** or ZnSO_(4) treatment showed a marked improvement in testicular antioxidant status and hormone levels,as well as a positive effect on the histology of the pituitary and *** combination of both treatments appeared to be more *** affinity of DEHP to bind to androgen receptors may lead to disruption of androgen receptor signaling,which can further result in dysfunction of hormones related to ***,NAC is more likely to form stronger binding interactions with follicle stimulating hormone and luteinizing hormone receptors,as well as gonadotropin-releasing hormone receptors,when compared to ***:The pos

关键词： Di-2-ethylhexyl phthalate Testosterone Androgen receptor 5α-reductase Oestrogen Luteinizing hormone

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Nutrient restriction-activated Fra-2 promotes tumor progression via IGF1R in miR-15a downmodulated pancreatic ductal adenocarcinoma

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Signal Transduction and Targeted Therapy 2024年第3期9卷 1132-1146页

作者： Gian Luca Rampioni Vinciguerra Marina Capece Luca Reggiani Bonetti Giovanni Nigita Federica Calore Sydney Rentsch Paolo Magistri Roberto Ballarin Fabrizio Di Benedetto Rosario Distefano Roberto Cirombella Andrea Vecchione Barbara Belletti Gustavo Baldassarre Francesca Lovat Carlo M.Croce department of Cancer Biology and Genetics and Comprehensive Cancer Center The Ohio State UniversityColumbus 43210 OHUSA department of Clinical and molecular Medicine Faculty of Medicine and PsychologySant’Andrea HospitalUniversity of Rome“Sapienza”Rome 00189Italy department of Diagnostic Clinic and Public Health MedicineUniversity of Modena and Reggio EmiliaModena 41100Italy Hepato-pancreato-biliary Surgery and Liver Transplantation Unit University of Modena and Reggio EmiliaModena 41100Italy Division of molecular Oncology Centro di Riferimento Oncologico di Aviano(CRO)Istituto di Ricovero e Cura a Carattere Scientifico(IRCCS)National Cancer InstituteAviano 33081Italy

Pancreatic ductal adenocarcinoma(PDAC)is a lethal disease,characterized by an intense desmoplastic reaction that compresses blood vessels and limits nutrient *** aggressiveness largely relies on its extraordinary capability to thrive and progress in a challenging tumor *** of the onco-suppressor miR-15a has been extensively documented in ***,we identified the transcription factor Fos-related antigen-2(Fra-2)as a miR-15a target mediating the adaptive mechanism of PDAC to nutrient *** report that the IGF1 signaling pathway was enhanced in nutrient deprived PDAC cells and that Fra-2 and IGF1R were significantly overexpressed in miR-15a downmodulated PDAC ***,we discovered that miR-15a repressed IGF1R expression via Fra-2 *** miR-15a-low context,IGF1R hyperactivated mTOR,modulated the autophagic flux and sustained PDAC growth in nutrient *** a genetic mouse model,Mir15aKO PDAC showed Fra-2 and Igf1r upregulation and mTOR activation in response to diet ***,nutrient restriction improved the efficacy of IGF1R inhibition in a Fra-2 dependent ***,our results point to a crucial role of Fra-2 in the cellular stress response due to nutrient restriction typical of pancreatic cancer and support IGF1R as a promising and vulnerable target in miR-15a downmodulated PDAC.

关键词： IGF1R Fra miR

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Emergence of taurine as a therapeutic agent for neurological disorders

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Neural Regeneration Research 2024年第1期19卷 62-68页

作者： Ashok Jangra Priyanka Gola Jiten Singh Pooja Gond Swarnabha Ghosh Mahesh Rachamalla Abhijit Dey Danish Iqbal Mehnaz Kamal Punya Sachdeva Saurabh Kumar Jha Shreesh Ojha Dinesh Kumar Niraj Kumar Jha Hitesh Chopra Shing Cheng Tan department of Pharmaceutical Sciences Central University of HaryanaMahendergarhHaryanaIndia department of Biology University of SaskatchewanSaskatoonSKCanada department of Life Sciences Presidency UniversityKolkataWest BengalIndia department of Health Information Management College of Applied Medical SciencesBuraydah Private CollegesBuraydahSaudi Arabia department of Pharmaceutical Chemistry College of PharmacyPrince Sattam Bin Abdulaziz UniversityAl-KharjSaudi Arabia GloNeuro Vishwakarma RoadNoidaIndia department of Biotechnology School of Engineering&Technology(SET)Sharda UniversityGreater NoidaUttar PradeshIndia department of pharmacology and Therapeutics College of Medicine and Health SciencesUnited Arab Emirates UniversityAl AinUnited Arab Emirates School of Bioengineering&Biosciences Lovely Professional UniversityPhagwaraIndia department of Biotechnology School of Applied&Life Sciences(SALS)Uttaranchal UniversityDehradunIndia Chitkara College of Pharmacy Chitkara UniversityPunjabIndia UKM Medical molecular Biology Institute Universiti Kebangsaan MalaysiaKuala LumpurMalaysia

Taurine is a sulfur-containing,semi-essential amino acid that occurs naturally in the *** alternates between inflammation and oxidative stress-mediated injury in various disease *** part of its limiting functions,taurine also modulates endoplasmic reticulum stress,Ca^(2+)homeostasis,and neuronal activity at the molecular *** effectively protects against a number of neurological disorders,including stro ke,epilepsy,cerebral ischemia,memory dysfunction,and spinal cord *** various therapies are available,effective management of these disorders remains a global *** 30 million people are affected *** design of taurine fo rmation co uld lead to potential drugs/supplements for the health maintenance and treatment of central nervous system *** general neuroprotective effects of taurine and the various possible underlying mechanisms are discussed in this *** article is a good resource for understanding the general effects of taurine on various *** the strong evidence for the neuropharmacological efficacy of taurine in various experimental paradigms,it is concluded that this molecule should be considered and further investigated as a potential candidate for neurotherapeutics,with emphasis on mechanism and clinical studies to determine efficacy.

关键词： antioxidant epilepsy γ-amino butyric acid neurodegenerative disorders neuroprotection oxidative stress spinal cord injury taurine

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Ultra-high-performance liquid chromatography-quadrupole time-of-flight-mass spectrometry-characterized extract of Aerides odorata Lour alleviates paracetamol-induced hepatotoxicity in animal model evidenced by biochemical,molecular, and computational studi

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Animal Models and Experimental Medicine 2024年第04期 497-522页

作者： A.M.Abu Ahmed Md.Atiar Rahman Farjana Sharmen A.S.M.Ali Reza Md.Shahidul Islam Md.Mamunur Rashid Md.Khalid Juhani Rafi Tanvir Ahmed Siddiqui Md.Muzahid Ahmed Ezaj Srabonti Saha Md.Nazim Uddin Walla Alelwani department of Genetic Engineering and Biotechnology University of Chittagong department of Biochemistry and molecular Biology University of Chittagong department of Pharmacy I nternational Islami University Chittagong Institute of Food Science and Technology Bangladesh Council of Scientific and Industrial Research department of Biochemistry College of ScienceUniversity of Jeddah

Background : Many kinds of orchids have significant health benefits although adequate research on their biological functions is yet to be carried out. This study investigated the paracetamol-i nduced liver damage–protecting effect of epiphytic Aerides odorata methanol extract(AODE).Methods : The protective effects of AODE were studied by analyzing its effect on liver function parameters, messenger RNA(mRNA) expression, and tissue histopathological architecture. The results were confirmed by ligand–receptor interaction of molecular docking and multitarget interaction of network pharmacological *** : AODE significantly( p pharmacology analysis identified the top 10 hub genes, namely AKT1(protein kinase B), CTNNB1(catenin beta-1), SRC(proto-oncogene c-Src), TNF(tumor necrosis factor), EGFR(epidermal growth factor receptor), HSP90AA1( heat shock protein 90α),MAPK3(mitogen-activated protein kinase 3), STAT3(signal transducer and activator

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The evolution of cancer genomic medicine in Japan and the role of the National Cancer Center Japan

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Cancer Biology & Medicine 2024年第1期21卷 29-44页

作者： Teruhiko Yoshida Yasushi Yatabe Ken Kato Genichiro Ishii Akinobu Hamada Hiroyuki Mano Kuniko Sunami Noboru Yamamoto Takashi Kohno department of Genetic Medicine and Services National Cancer Center HospitalTokyo 104-0045Japan department of Diagnostic Pathology National Cancer Center HospitalTokyo 104-0045Japan Clinical Research Support Offce Clinical Research Coordinating SectionBiobank Translational Research Support SectionNational Cancer Center HospitalTokyo 104-0045Japan department of Pathology and Clinical Laboratories National Cancer Center Hospital EastChiba 277-8577Japan Division of molecular pharmacology National Cancer Center Research InstituteTokyo 104-0045Japan National Cancer Center Research Institute Tokyo 104-0045Japan department of Laboratory Medicine National Cancer Center HospitalTokyo 104-0045Japan department of Experimental Therapeutics National Cancer Center HospitalTokyo 104-0045Japan Division of Genome Biology National Cancer Center Research InstituteTokyo 104-0045Japan

The journey to implement cancer genomic medicine(CGM)in oncology practice began in the 1980s,which is considered the dawn of genetic and genomic cancer *** the time,a variety of activating oncogenic alterations and their functional significance were unveiled in cancer cells,which led to the development of molecular targeted therapies in the 2000s and *** CGM is still a relatively new discipline and it is difficult to predict to what extent CGM will benefit the diverse pool of cancer patients,the National Cancer Center(NCC)of Japan has already contributed considerably to CGM advancement for the conquest of *** back at these past achievements of the NCC,we predict that the future of CGM will involve the following:1)A biobank of paired cancerous and non-cancerous tissues and cells from various cancer types and stages will be *** quantity and quality of these samples will be compatible with omics *** biobank samples will be linked to longitudinal clinical information.2)New technologies,such as whole-genome sequencing and artificial intelligence,will be introduced and new bioresources for functional and pharmacologic analyses(e.g.,a patient-derived xenograft library)will be systematically deployed.3)Fast and bidirectional translational research(bench-to-bedside and bedside-to-bench)performed by basic researchers and clinical investigators,preferably working alongside each other at the same institution,will be implemented;4)Close collaborations between academia,industry,regulatory bodies,and funding agencies will be established.5)There will be an investment in the other branch of CGM,personalized preventive medicine,based on the individual's genetic predisposition to cancer.

关键词： Cancer genomic medicine biobank patient-derived xenograft multi-gene panel test whole genome sequencing

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The fate of medications evaluated for ischemic stroke pharmacotherapy over the period 1995–2015

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Acta Pharmaceutica Sinica B 2016年第6期6卷 522-530页

作者： Xiaoling Chen Kewei Wang department of molecular and cellular pharmacology State Key Laboratory of Natural and Biomimetic Drugs Peking University School of Pharmaceutical Sciences department of pharmacology Qingdao University School of Pharmacy

Stroke is a brain damage caused by a loss of blood supply to a portion of the brain, which requires prompt and effective treatment. The current pharmacotherapy for ischemic stroke primarily relies on thrombolysis using recombinant tissue plasminogen activators(rt-PAs) to breakdown blood clots. Neuroprotective agents that inhibit excitatory neurotransmitters are also used to treat ischemic stroke but have failed to translate into clinical benefits. This poses a major challenge in biomedical research to understand what causes the progressive brain cell death after stroke and how to develop an effective pharmacotherapy for stroke. This brief review analyzes the fate of about 430 potentially useful stroke medications over the period 1995–2015and describes in detail those that successfully reached the market. Hopefully, the information from this analysis will shed light on how future stroke research can improve stroke drug discovery.

关键词： Thrombosis Neuroprotective agent Ischemic stroke Traditional Chinese medicine Non-NMDA mechanism Ion channel

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A mutation in TBXT causes congenital vertebral malformations in humans and mice

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Journal of Genetics and Genomics 2024年第4期51卷 433-442页

作者： Shuxia Chen Yunping Lei Yajun Yang Chennan Liu Lele Kuang Li Jin Richard HFinnell Xueyan Yang Hongyan Wang Obstetrics and Gynecology Hospital State Key Laboratory of Genetic Engineering at School of Life SciencesKey Laboratory of Reproduction Regulation of NPFPCInstitute of Reproduction and DevelopmentFudan UniversityShanghai 200438China Shanghai Key Laboratory of Metabolic Remodeling and Health Institute of Metabolism and Integrative BiologyFudan UniversityShanghai 200438China Center for Precision Environmental Health Department of Molecular and Cellular BiologyBaylor College of MedicineHoustonTX 77030USA MOE Key Laboratory of Contemporary Anthropology School of Life SciencesFudan UniversityShanghai 200438China department of Assisted Reproduction Xinhua HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200092China Children’s Hospital Fudan University399 Wanyuan RoadShanghai 201102China

T-box transcription factor T(TBXT;T)is required for mesodermal formation and axial skeletal *** it has been extensively studied in various model organisms,human congenital vertebral malformations(CVMs)involving T are not well ***,we report a family with 15 CVM patients distributed across 4 *** affected individuals carry a heterozygous mutation,T c.596A>G(p.Q199R),which is not found in unaffected family members,indicating co-segregation of the genotype and *** vitro assays show that T p.Q199R increases the nucleocytoplasmic ratio and enhances its DNA-binding affinity,but reduces its transcriptional activity compared to the *** determine the pathogenicity of this mutation in vivo,we generated a Q199R knock-in mouse model that recapitulates the human CVM *** heterozygous Q199R mice show subtle kinked or shortened tails,while homozygous mice exhibit tail filaments and severe vertebral ***,we show that the Q199R mutation in T causes CVM in humans and mice,providing previously unreported evidence supporting the function of T in the genetic etiology of human CVM.

关键词： Congenital vertebral malformation TBXT T gene Loss-of-function mutation

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Treatment with β-sitosterol ameliorates the effects of cerebral ischemia/reperfusion injury by suppressing cholesterol overload, endoplasmic reticulum stress, and apoptosis

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Neural Regeneration Research 2024年第3期19卷 642-649页

作者： Xiuling Tang Tao Yan Saiying Wang Qingqing Liu Qi Yang Yongqiang Zhang Yujiao Li Yumei Wu Shuibing Liu Yulong Ma Le Yang Precision Pharmacy&Drug Development Center Department of PharmacyTangdu HospitalAir Force Medical UniversityXi’anShaanxi ProvinceChina department of Clinical Pharmacy Jinling HospitalMedical School of Nanjing UniversityNanjingJiangsu ProvinceChina department of pharmacology School of PharmacyAir Force Medical UniversityXi’anShaanxi ProvinceChina department of Anesthesiology The First Medical Center of Chinese PLA General HospitalBeijingChina department of Anatomy Histology and Embryology and K.K.Leung Brain Research CentreAir Force Medical UniversityXi’anShaanxi ProvinceChina

β-Sitosterol is a type of phytosterol that occurs naturally in *** studies have shown that it has anti-oxidant,anti-hyperlipidemic,anti-inflammatory,immunomodulatory,and anti-tumor effects,but it is unknown whetherβ-sitosterol treatment reduces the effects of ischemic *** we found that,in a mouse model of ischemic stroke induced by middle cerebral artery occlusion,β-sitosterol reduced the volume of cerebral infarction and brain edema,reduced neuronal apoptosis in brain tissue,and alleviated neurological dysfunction;moreover,β-sitosterol increased the activity of oxygen-and glucose-deprived cerebral cortex neurons and reduced *** investigation showed that the neuroprotective effects ofβ-sitosterol may be related to inhibition of endoplasmic reticulum stress caused by intracellular cholesterol accumulation after ischemic *** addition,β-sitosterol showed high affinity for NPC1L1,a key transporter of cholesterol,and antagonized its *** conclusion,β-sitosterol may help treat ischemic stroke by inhibiting neuronal intracellular cholesterol overload/endoplasmic reticulum stress/apoptosis signaling pathways.

关键词： apoptosis blood-brain barrier β-sitosterol cerebral ischemia/reperfusion injury cholesterol overload cholesterol transport endoplasmic reticulum stress ischemic stroke molecular docking NPC1L1

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Microglial response to aging and neuroinflammation in the development of neurodegenerative diseases

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Neural Regeneration Research 2024年第6期19卷 1241-1248页

作者： Tingting Han Yuxiang Xu Lin Sun Makoto Hashimoto Jianshe Wei Institute for Brain Sciences Research School of Life SciencesHenan UniversityKaifengHenan ProvinceChina College of Chemistry and molecular Sciences Henan UniversityKaifengHenan ProvinceChina department of Basic Technology Tokyo Metropolitan Institute of Medical ScienceTokyoJapan.

cellular senescence and chronic inflammation in response to aging are considered to be indicators of brain aging;they have a great impact on the aging process and are the main risk factors for *** the microglial response to aging and neuroinflammation in neurodegenerative diseases will help understand the importance of microglia in neurodegenerative *** review describes the origin and function of microglia and focuses on the role of different states of the microglial response to aging and chronic inflammation on the occurrence and development of neurodegenerative diseases,including Alzheimer's disease,Huntington's chorea,and Parkinson's *** review also describes the potential benefits of treating neurodegenerative diseases by modulating changes in microglial ***,inducing a shift from the neurotoxic to neuroprotective microglial state in neurodegenerative diseases induced by aging and chronic inflammation holds promise for the treatment of neurodegenerative diseases in the future.

关键词： aging Alzheimer's disease cytokines Huntington's disease microglia neurodegenerative diseases neuroinflammation neuroprotection neurotoxicity Parkinson's disease

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