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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 83-105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 Malaysia department of Bio-Sciences School of Bio-Sciences&Technology (SBST)Vellore Institute of Technology (VIT) department of Internal medicine University of Alabama at Birmingham department of Microbiology University of Delhi (South Campus) department of Biotechnology Indian Institute of TechnologyHyderabad (IIT-H) Bio Analytical Lab Meso Scale Discovery department of pharmacology Government Medical College Laboratory of Translational medicine and Nanotherapeutics Department of Human Genetics and Molecular MedicineSchool of Health SciencesCentral University of Punjab department of Biochemistry Kakatiya Medical College

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 cardiomyopathies. Despite significant progress in reducing mortality rates from cardiovascular diseases(CVDs), heart failure remains a major cause of increased morbidity among diabetic patients. These 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 treatment. While 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 scenarios. Although conventional medications have been widely used in DHC patients, they raise several concerns regarding various physiological aspects. Modern 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 therapies. This 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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Gambogenic acid induces apoptosis via upregulation of Noxa in oral squamous cell carcinoma

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Chinese Journal of Natural medicines 2024年第7期22卷 632-642页

作者： CHENG Xinran FENG Mengyuan ZHANG Anjie GUO Jian GONG Yunlai HU Xiaohui HAN Quanbin LI Shengbao YU Xianjun department of Gastroenterology Taihe HospitalHubei University of MedicineShiyan 442000China Laboratory of Inflammation and Molecular pharmacology School of Basic Medical Sciences&Biomedical Research InstituteHubei Key Laboratory of Wudang Local Chinese Medicine ResearchSchool of PharmacyHubei University of MedicineShiyan 442000China Inflammation-Cancer Transformation and Wudang Chinese medicine Research Hubei Talent Introduction and Innovation Demonstration BaseHubei University of MedicineShiyan 442000China school of Chinese medicine Hong Kong Baptist UniversityHong Kong 999077China

Gambogenic acid(GNA),a bioactive compound derived from the resin of Garcinia hanburyi,has demonstrated significant antitumor ***,its mechanisms of action in oral squamous cell carcinoma(OSCC)remain largely *** study aimed to elucidate the apoptotic effects of GNA on OSCC cell lines CAL-27 and *** results indicated that GNA induced apoptosis by upregulating the pro-apoptotic protein *** investigations revealed that GNA treatment led to the generation of reactive oxygen species(ROS),which activated endoplasmic reticulum(ER)stress,culminating in cell *** of ROS production and ER stress pathways significantly mitigated GNA-induced Noxa upregulation and subsequent ***,in vivo studies using a murine xenograft model demonstrated that GNA administration effectively inhibited the growth of CAL-27 ***,these findings underscore GNA’s potential as a therapeutic agent for the treatment of OSCC.

关键词： Oral squamous cell carcinoma Gambogenic acid Apoptosis Noxa ROS/ER stress

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Vitamin D binding protein in psychiatric and neurological disorders:Implications for diagnosis and treatment

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Genes & Diseases 2024年第5期11卷 324-334页

作者： Ling Li Bing Han Yan Kong Gaojia Zhang Zhijun Zhang Research Institution of Neuropsychiatry School of MedicineSoutheast UniversityNanjingJiangsu 210009China department of Neurology Affiliated Zhongda HospitalNanjingJiangsu 210009China department of pharmacology Jiangsu Provincial Key Laboratory of Critical Care MedicineSchool of MedicineSoutheast UniversityNanjingJiangsu 210009China department of Biochemistry and Molecular Biology School of MedicineSoutheast UniversityNanjingJiangsu 210009China Brain Cognition and Brain Disease Institute Department of Mental Health and Public HealthFaculty of Life and Health SciencesShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong 518055China

Vitamin D binding protein(VDBP)serves as a key transporter protein responsible for binding and delivering vitamin D and its metabolites to target *** plays a crucial part in the inflammatory reaction following tissue damage and is engaged in actin *** research has shed light on its potential role in various diseases,leading to a growing interest in understanding the implications of VDBP in psychiatric and neurological *** purpose of this review was to provide a summary of the existing understanding regarding the involvement of VDBP in neurological and psychiatric *** examining the intricate interplay between VDBP and these disorders,this review contributes to a deeper understanding of underlying mechanisms and potential therapeutic *** gained from the study of VDBP could pave the way for novel strategies in the diagnosis,prognosis,and treatment of psychiatric and neurological disorders.

关键词： Neurological disorder Polymorphism Psychiatric disorder Structure Vitamin D binding protein

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Modeling tuberous sclerosis complex with human induced pluripotent stem cells

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World Journal of Pediatrics 2024年第3期20卷 208-218页

作者： Weibo Niu Benjamin Siciliano Zhexing Wen department of Psychiatry and Behavioral Sciences Emory University School of MedicineWhitehead Research Building 447615 Michael StreetAtlantaGA 30322USA The Graduate Program in Molecular and Systems pharmacology Laney Graduate SchoolEmory UniversityAtlanta.GA 30322.USA department of Cell Biology Emory University School of MedicineWhitehead Research Building 447615 Michael StreetAtlantaGA30322USA department of Neurology Emory University School of MedicineWhitehead Research Building 447.615 Michael StreetAtlantaGA 30322USA

Background Tuberous sclerosis complex(TSC)is an autosomal dominant genetic disorder with a birth incidence of I:6000 in the United States that is characterized by the growth of non-cancerous tumors in multiple organ systems including the brain,kidneys,lungs,and ***,TSCis also associated with signicant neurological manifestations including epilepsy TSC-associated neuropsychiatric disorders,intellectual disabilities,and autism spectrum *** in the TSCI or TSC2 genes are well-established causes of TSC,which lead to TSC1/TSC2 deficiency in organs and hyper-activation of the mammalian target of rapamycin signaling *** models have been widely used to study the effect of TSCl/2 genes on the development and function of the *** considerable progress in understanding the molecular mechanisms underlying TSC in animal models,a human-specific model is urgently needed to investigate the effects of TSCl/2 mutations that are unique to human *** sources Literature reviews and research articles were published in PubMed-indexed *** Human-induced pluripotent stem cells(iPSCs),which capture risk alleles that are identical to their donors and have the capacity to differentiate into virtually any cell type in the human body,pave the way for the empirical study of previously inaccessible biological systems such as the developing human *** In this review,we present an overview of the recent progress in modeling TSC with human iPSC models,the existing limitations,and potential directions for future research.

关键词： Induced pluripotent stem cells Three-dimensional cultures Tuberous sclerosis complex Two-dimensional cultures

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Black radish root extract alleviates sodium valproate-induced liver damage via inhibiting mitochondrial membrane potential collapse and oxidative stress in mice

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Asian Pacific Journal of Tropical Biomedicine 2024年第7期14卷 298-306页

作者： Mohammad Hadi Zarei Sami Akbulut Maryam Zafari Elham Saghaei Zahra Lorigooini Hossein AminiKhoei Somaye Khosravi Elham Bijad Medical Plants Research Center Basic Health Sciences InstituteShahrekord University of Medical SciencesShahrekordIran department of Liver Transplant Institute and Biostatistics Inonu University Faculty of Medicine44280MalatyaTurkey Student Research Committee Shahrekord University of Medical SciencesShahrekordIran Physiology and pharmacology department School of MedicineShahrekord University of Medical SciencesShahrekordIran department of Anatomical Sciences School of MedicineShahrekord University of Medical SciencesShahrekordIran

Objective:To explore the effect of black radish(Raphanus sativus *** niger)root extract on liver enzymes,oxidative stress,and histopathological alterations in mice with sodium valproate-induced ***:Thirty-two mice were divided into four groups:the control group received drinking water by gavage,the second group was administered with 100 mg/kg of sodium valproate,the third group received 300 mg/kg of black radish root extract,and the fourth group was given both sodium valproate(100 mg/kg)and black radish root extract(300 mg/kg).After 28 days,the mice were euthanized,and serum levels of aspartate aminotransferase(AST),alanine aminotransferase(ALT),and alkaline phosphatase(ALP),along with liver malondialdehyde(MDA),reactive oxygen species(ROS),mitochondrial parameters,tumor necrosis factor-alpha(TNF-α)gene expression,and histopathological changes were ***:Sodium valproate caused hepatic damage in mice,characterized by elevated serum levels of liver enzymes,increased MDA and ROS levels and TNF-αgene expression,as well as histopathological *** black radish root extract significantly alleviated sodium valproate-caused hepatic injury by decreasing the serum levels of ALT and AST,MDA,ROS,TNF-αgene expression,as well as mitochondrial impairment,but did not have a significant effect on sodium valproate-induced histopathological ***:The black radish root extract demonstrates protective effects against sodium valproate-induced liver injury,possibly through mitigating oxidative stress,mitochondrial impairment,and inflammatory mediator expression.

关键词： Black radish Raphanus sativus Sodium valproate Hepatotoxicity Oxidative stress Anti-inflammation

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Understanding the Novel Approach of Nanoferroptosis for Cancer Therapy

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Nano-Micro Letters 2024年第9期16卷 501-556页

作者： Afsana Sheikh Prashant Kesharwani Waleed H.Almalki Salem Salman Almujri Linxin Dai Zhe‑Sheng Chen Amirhossein Sahebkar Fei Gao department of Pharmaceutics School of Pharmaceutical Education and ResearchJamia HamdardNew Delhi 110062India department of pharmacology and Toxicology Faculty of PharmacyUmm Al-Qura UniversityMakkahSaudi Arabia department of pharmacology College of PharmacyKing Khalid University61421 Asir‑AbhaSaudi Arabia State Key Laboratory of Southwestern Chinese medicine Resources Pharmacy SchoolChengdu University of Traditional Chinese MedicineChengdu 611130People’s Republic of China department of Pharmaceutical Sciences College of Pharmacy and Health SciencesSt.John’s UniversityNew York 11439USA Biotechnology Research Center Pharmaceutical Technology InstituteMashhad University of Medical SciencesMashhadIran Applied Biomedical Research Center Mashhad University of Medical SciencesMashhadIran

As a new form of regulated cell death,ferroptosis has unraveled the unsolicited theory of intrinsic apoptosis resistance by cancer *** molecular mechanism of ferroptosis depends on the induction of oxidative stress through excessive reactive oxygen species accumulation and glutathione depletion to damage the structural integrity of *** to their high loading and structural tunability,nanocarriers can escort the delivery of ferro-therapeutics to the desired site through enhanced permeation or retention effect or by active *** review shed light on the necessity of iron in cancer cell growth and the fascinating features of ferroptosis in regulating the cell cycle and ***,we discussed the effect of ferroptosis-mediated therapy using nanoplatforms and their chemical basis in overcoming the barriers to cancer therapy.

关键词： Ferroptosis Nanoparticles Ferrotherapy Cancer Genes Nanotechnology Toxicity Reactive oxygen species

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Magnesium lithospermate B enhances the potential of human-induced pluripotent stem cell-derived cardiomyocytes for myocardial repair

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中华医学杂志(英文版) 2024年第15期137卷 1857-1869页

作者： Fan Chengming Qin Kele Iroegbu Chukwuemeka Daniel Xiang Kun Gong Yibo Guan Qing Wang Wenxiang Peng Jun Guo Jianjun Wu Xun Yang Jinfu department of Cardiovascular Surgery The Second Xiangya Hospital Central South University Changsha Hunan China department of pharmacology Xiangya School of Pharmaceutical Sciences Central South University Changsha Hunan China Hunan Fangsheng Pharmaceutical Co. Ltd. Changsha Hunan China department of Thoracic Surgery The Affiliated Cancer Hospital of Xiangya School of Medicine Central South University Changsha Hunan China

Background: We previously reported that activation of the cell cycle in human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) enhances their remuscularization capacity after human cardiac muscle patch transplantation in infarcted mouse hearts. Herein, we sought to identify the effect of magnesium lithospermate B (MLB) on hiPSC-CMs during myocardial repair using a myocardial infarction (MI) mouse ***: In C57BL/6 mice, MI was surgically induced by ligating the left anterior descending coronary artery. The mice were randomly divided into five groups (n = 10 per group); a MI group (treated with phosphate-buffered saline only), a hiPSC-CMs group, a MLB group, a hiPSC-CMs + MLB group, and a Sham operation group. Cardiac function and MLB therapeutic efficacy were evaluated by echocardiography and histochemical staining 4 weeks after surgery. To identify the associated mechanism, nuclear factor (NF)-κB p65 and intercellular cell adhesion molecule-1 (ICAM1) signals, cell adhesion ability, generation of reactive oxygen species, and rates of apoptosis were detected in human umbilical vein endothelial cells (HUVECs) and ***: After 4 weeks of transplantation, the number of cells that engrafted in the hiPSC-CMs + MLB group was about five times higher than those in the hiPSC-CMs group. Additionally, MLB treatment significantly reduced tohoku hospital pediatrics-1 (THP-1) cell adhesion, ICAM1 expression, NF-κB nuclear translocation, reactive oxygen species production, NF-κB p65 phosphorylation, and cell apoptosis in HUVECs cultured under hypoxia. Similarly, treatment with MLB significantly inhibited the apoptosis of hiPSC-CMsvia enhancing signal transducer and activator of transcription 3 (STAT3) phosphorylation and B-cell lymphoma-2 (BCL2) expression, promoting STAT3 nuclear translocation, and downregulating BCL2-Associated X, dual specificity phosphatase 2 (DUSP2), and cleaved-caspase-3 expression under hypoxia. Furthermore, MLB significan

关键词： Myocardial infarction Cell therapy Induced pluripotent stem cells Magnesium lithospermate B Cardiomyocyte Disease modeling hiPSC-CMs

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Acupoint Selection Standards of Auricular Therapy in the Treatment of Maintenance Hemodialysis Insomnia Based on Data Mining

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World Journal of Traditional Chinese medicine 2024年第1期10卷 53-64页

作者： Jun-Xin Wang Bing-Qian Zou Yu-Feng Chen Cheng-Long Wang Wei-Hong Li Xue-Ling Ma Xiang-Di Liu department of TCM Nursing School of NursingBeijing University of Chinese MedicineBeijingChina department of Healthcare Beijing HospitalNational Center of GerontologyInstitute of Geriatric MedicineChinese Academy of Medical SciencesP.R.China pharmacology of Integrated Chinese and Western medicine School of Traditional Chinese MedicineBeijing University of Chinese MedicineBeijingChina Beijing Key Laboratory of TCM Syndrome and Formula School of Traditional Chinese MedicineBeijing University of Chinese MedicineBeijingChina Key Laboratory of TCM Syndrome and Formula School of Traditional Chinese MedicineBeijing University of Chinese MedicineMinistry of EducationBeijingChina

Background:Insomnia is a high-incidence complication in patients undergoing maintenance hemodialysis(MHD).Auricular therapy can effectively improve sleep with few adverse *** selection affects the impact of auricular ***,there is currently a lack of analysis on the standards of acupoint *** study used data mining technology to investigate the acupoint selection principles and characteristics of auricular therapy for the treatment of MHD-related ***:The objective of the study is to explore the standards of acupoint selection in auricular therapy for the treatment of MHD-related insomnia through data mining *** and Methods:We searched three English(PubMed,WOS,and Embase)and four Chinese(CNKI,VIP,Wangfang,and CBM)databases for studies on auricular therapy for MHD-related insomnia from self-establishment to November 14,***:Eighty-one publications were involved,which included 33 *** most common auricular points in patients with MHD-related insomnia were the Shenmen,heart,and kidney *** applications involved the visceral,nervous system,and specific *** effective clusters and two clusters were obtained through cluster analysis,including specific auricular points for insomnia,such as the multi-dream area,neurasthenia area,deep sleep point,and anterior ear *** network analysis showed that the core auricular acupoint combinations for the intervention of MHD-related insomnia were Shenmen with kidney,Shenmen with heart,heart with kidney,heart with Shenmen,and heart and Shenmen with ***:The selection of auricular points for the treatment of MHD-related insomnia was guided by the heart theory of traditional Chinese *** treatment attaches importance to the use of the multi-dream area,neurasthenia area,and other acupoints.

关键词： Acupoint selection standards auricular therapy data mining insomnia maintenance hemodialysis

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Repurposing lansoprazole to alleviate metabolic syndrome via PHOSPHO1 inhibition

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Acta Pharmaceutica Sinica B 2024年第4期14卷 1711-1725页

作者： Yingting Wu Jiaqi Xin Xinyu Li Ting Yang Yi Liu Yongsheng Zhao Wen Xie Mengxi Jiang department of pharmacology School of Basic Medical SciencesCapital Medical UniversityBeijing 100069China department of Traditional Chinese medicine Capital Medical UniversityBeijing 100069China Center for Pharmacogenetics and department of Pharmaceutical Sciences University of PittsburghPittsburghPA 15261USA Advanced Innovation Center for Human Brain Protection Capital Medical UniversityBeijing 100069China

Drug repurposing offers an efficient approach to therapeutic *** this study,our bioinformatic analysis first predicted an association between obesity and lansoprazole(LPZ),a commonly prescribed drug for gastrointestinal *** went on to show that LPZ treatment increased energy expenditure and alleviated the high-fat diet-induced obesity,insulin resistance,and hepatic stea-tosis in *** with LPZ elicited thermogenic gene expression and mitochondrial respiration in primary adipocytes,and induced cold tolerance in cold-exposed mice,suggesting the activity of LPZ in promoting adipose thermogenesis and energy ***,LPZ is an efficient inhibitor of adipose phosphocholine phosphatase 1(PHOSPHOI)and produces metabolic benefits in a PHOS-PHO1-dependent *** results suggested that LPZ may stimulate adipose thermogenesis by inhi-biting the conversion of 2-arachidonoylglycerol-lysophosphatidic acid(2-AG-LPA)to 2-arachidonoylglycerol(2-AG)and reduce the activity of the thermogenic-suppressive cannabinoid recep-tor *** summary,we have uncovered a novel therapeutic indication and mechanism of LPZ in managing obesity and its related metabolic syndrome,and identified a potential metabolic basis by which LPZ improves energy metabolism.

关键词： Lansoprazole Proton pump inhibitors Adipose thermogenesis Energy expenditure Metabolic syndrome PHOSPHO1 inhibitor Cannabinoid receptor signaling Drug repurposing

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Targeting PKM2 signaling cascade with salvianic acid A normalizes tumor blood vessels to facilitate chemotherapeutic drug delivery

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2077-2096页

作者： Cheng Qian Yueke Zhou Teng Zhang Guanglu Dong Mengyao Song Yu Tang Zhonghong Wei Suyun Yu Qiuhong Shen Wenxing Chen Jaesung P.Choi Juming Yan Chongjin Zhong Li Wan Jia Li Aiyun Wang Yin Lu Yang Zhao Jiangsu Key Laboratory for pharmacology and Safety Evaluation of Chinese Materia Medica Nanjing University of Chinese MedicineNanjing 210023China school of medicine&Holistic Integrative medicine Nanjing University of Chinese MedicineNanjing 210023China Centre for Inflammation Faculty of ScienceCentenary InstituteSchool of Life SciencesUniversity of Technology SydneySydney NSW 2050Australia Jiangsu Key Laboratory of Immunity and Metabolism Department of Pathogenic Biology and ImmunologyNational Experimental Demonstration Center for Basic Medicine EducationXuzhou Laboratory of Infection and ImmunityXuzhou Medical UniversityXuzhou 221004China department of General Surgery Jiangsu Province Hospital of Chinese MedicineAffiliated Hospital of Nanjing University of Chinese MedicineNanjing 210029China Macquarie Medical school Faculty of MedicineHuman Health SciencesMacquarie UniversitySydney NSW 2109Australia

Aberrant tumor blood vessels are prone to propel the malignant progression of tumors,and targeting abnormal metabolism of tumor endothelial cells emerges as a promising option to achieve vascular normalization and antagonize tumor ***,we demonstrated that salvianic acid A(SAA)played a pivotal role in contributing to vascular normalization in the tumor-bearing mice,thereby improving delivery and effectiveness of the chemotherapeutic *** was capable of inhibiting glycolysis and strengthening endothelial junctions in the human umbilical vein endothelial cells(HUVECs)exposed to ***,SAA was inclined to directly bind to the glycolytic enzyme PKM2,leading to a dramatic decrease in endothelial *** importantly,SAA improved the endothelial integrity via activating theβ-Catenin/Claudin-5 signaling axis in a PKM2-dependent *** findings suggest that SAA may serve as a potent agent for inducing tumor vascular normalization.

关键词： Salvianic acid A Tumor vascular normalization PKM2 β-Catenin Claudin-5 Endothelial glycolysis Tight junctions Doxorubicin

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