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TRPC6 Knockout Alleviates Renal Fibrosis through PI3K/AKT/GSK3B Pathway

Current Medical Science 2024年第3期44卷 589-602页

作者： An-bang SUN Fang-hua LI Lin ZHU Xi-xi ZENG Min ZHU Qing-hua LEI Yan-hong LIAO department of anatomy School of Basic MedicineTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China department of Transfusion Medicine Wuhan Hospital of Traditional Chinese and Western MedicineTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China department of Nephrology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou450052China department of Thoracic Surgery Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China National Basic Medical Teaching Demonstration Center Tongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China Key Laboratory of Neurological Diseases of Ministry of Education Tongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China

Objective Renal fibrosis is the ultimate pathway of various forms of acute and chronic kidney ***,the knockout of transient receptor potential channel 6(TRPC6)has shown promise in alleviating renal ***,the regulatory impact of TRPC6 on renal fibrosis remains *** In vivo,TRPC6 knockout(TRPC6−/−)mice and age-matched 129 SvEv(WT)mice underwent unilateral renal ischemia-reperfusion(uIR)injury surgery on the left renal pedicle or sham *** and serum were collected on days 7,14,21,and 28 after *** vitro,primary tubular epithelial cells(PTECs)were isolated from TRPC6−/−and WT mice,followed by treatment with transforming growth factorβ1(TGFβ1)for 72 *** anti-fibrotic effect of TRPC6−/−and the underlying mechanisms were assessed through hematoxylin-eosin staining,Masson staining,immunostaining,qRT-PCR,and Western *** Increased TRPC6 expression was observed in uIR mice and PTECs treated with TGFβ***6−/−alleviated renal fibrosis by reducing the expression of fibrotic markers(Col-1,α-SMA,and vimentin),as well as decreasing the apoptosis and inflammation of PTECs during fibrotic progression both in vivo and in ***,we found that the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)/glycogen synthase kinase 3 beta(GSK3β)signaling pathway,a pivotal player in renal fibrosis,was down-regulated following TRPC6 *** These results suggest that the ablation of TRPC6 may mitigate renal fibrosis by inhibiting the apoptosis and inflammation of PTECs through down-regulation of the PI3K/AKT/GSK3β*** TRPC6 could be a novel therapeutic strategy for preventing chronic kidney disease.

关键词： transient receptor potential channel 6 ischemia-reperfusion injury renal fibrosis renal tubular epithelial cells

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A medium chain fatty acid, 6-hydroxyhexanoic acid (6-HHA), protects against obesity and insulin resistance

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Acta Pharmaceutica Sinica B 2024年第4期14卷 1892-1894页

作者： Sara C.Sebag Meihua Hao Qingwen Qian Chawin Upara Qiong Ding Min Zhu Jeffrey A.Banas Huojun Cao Liu Hong Ling Yang department of anatomy and Cell Biology University of Iowa Carver College of MedicineIowa CityIA 52242USA Fraternal Order of Eagles Diabetes Research Center University of Iowa Carver College of MedicineIowa CityIA 52242USA Pappajohn Biomedical Institute University of Iowa Carver College of MedicineIowa CityIA 52242USA Iowa Institute for Oral Health Research University of Iowa College of DentistryIowa CityIA 52242USA

To the Editor,Obesity,one of the most serious health concerns worldwide,exacerbates periodontitis pathogenesis and reduces the effectiveness of ***,periodontitis-associated inflammation disrupts systemic lipid and glucose homeostasis,the major risk factors for developing obesity-associated *** studies have demonstrated that certain supplemental dietary lipids such as dietary polyunsaturated fatty acids,have beneficial outcomes for diabetic and obese *** addition to dietary lipid supply,the oral and gut microbiota produce fatty acids(FAs)which provide the host with essential nutrients and aid in defense against *** medium chain FAs(MCFAs;6–12 carbons)are bacterial-derived lipids shown to have anti-inflammatory and insulin sensitization effects in diverse cell types such as ***,whether and to what extent oral microbiota-produced MCFAs may ameliorate obesity-associated metabolic dysfunction are largely unknown.

关键词： obesity dietary lipids

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Nitrosamines crisis in pharmaceuticals-Insights on toxicological implications,root causes and risk assessment:A systematic review

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Journal of Pharmaceutical Analysis 2024年第5期14卷 639-652页

作者： Hemanth P.R.Vikram Tegginamath Pramod Kumar Gunjan Kumar Narasimha M.Beeraka Rajashree Deka Sheik Mohammed Suhail Sandeep Jat Namitha Bannimath Gayatiri Padmanabhan Ravandur S.Chandan Pramod Kumar Bannimath Gurupadayya department of Pharmaceutical Chemistry JSS College of Pharmacy MysuruJSS Academy of Higher Education and Research(JSSAHER)Mysuru570015India Xenone Healthcare Pvt.Ltd. New Delhi110076India department of Pharmaceutics JSS College of Pharmacy MysuruJSS Academy of Higher Education and Research(JSSAHER)Mysuru570015India department of human anatomy I.M.Sechenov First Moscow State Medical University(Sechenov University)Moscow119991Russian Federation department of Pharmacology Raghavendra Institute of Pharmaceutical Education and Research(RIPER)Ananthapuramu515721India Herman B.Wells Center for Pediatric Research Department of PediatricsIndiana University School of MedicineIndianapolisIN46202USA Animal Physiology and Biochemistry Laboratory Department of ZoologyGauhati UniversityGuwahati781014India department of Pharmacology JSS College of Pharmacy MysuruJSS Academy of Higher Education and Research(JSSAHER)Mysuru570015India department of Pharmaceutical Analysis National Institute of Pharmaceutical Education and Research(NIPER)-GuwahatiChangsari781101India department of Pharmacology University of GalwayGalwayH91 TK33Ireland

The presence of N-nitroso compounds,particularly N-nitrosamines,in pharmaceutical products has raised global safety concerns due to their significant genotoxic and mutagenic *** systematic review investigates their toxicity in active pharmaceutical ingredients(APIs),drug products,and pharmaceutical excipients,along with novel analytical strategies for detection,root cause analysis,reformulation strategies,and regulatory guidelines for *** review emphasizes the molecular toxicity of N-nitroso compounds,focusing on genotoxic,mutagenic,carcinogenic,and other physiological ***,it addresses the ongoing nitrosamine crisis,the development of nitrosamine-free products,and the importance of sensitive detection methods and precise risk *** comprehensive overview will aid molecular biologists,analytical scientists,formulation scientists in research and development sector,and researchers involved in management of nitrosamine-induced toxicity and promoting safer pharmaceutical products.

关键词： Carcinogenicity Genotoxicity Mutagenicity Molecular toxicity Nitrosamine impurities Nitrosamine drug substance-related impurities

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A survey on the real-world clinical utilization of a traditional acupuncture in Republic of Korea:Sa-am acupuncture

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Journal of Integrative Medicine 2024年第5期22卷 570-578页

作者： Ji-Yeun Park Ye-Seul Lee Hi-Joon Park Seungmin Kathy Lee Ji-Won Lee Song-Yi Kim college of Korean Medicine Daejeon UniversityDaejeon 34520Republic of Korea Jaseng Spine and Joint Research Institute Jaseng Medical FoundationSeoul 06110Republic of Korea Acupuncture and Meridian Science Research Center Kyung Hee UniversitySeoul 02447Republic of Korea department of Korean Medicine Korean Medical CenterLusail 201184Qatar Virginia University of Integrative Medicine ViennaVA 22182USA department of anatomy and Acupoint College of Korean MedicineGachon UniversitySeongnamGyeonggi 13120Republic of Korea department of Ophthalmology Otolaryngologyand DermatologyCollege of Korean MedicineDongguk UniversityGoyangGyeonggi 10326Republic of Korea

Objective This study investigated the clinical details and usage of Sa-am acupuncture in Korean medicine clinics and explored how practicing Korean medicine doctors(KMDs)think about Sa-am *** We conducted a questionnaire-based survey of KMDs who utilize Sa-am acupuncture in their *** study comprehensively investigated issues related to clinical application of Sa-am acupuncture,needling techniques used during treatment,training methods,and directions for its future *** We analyzed 572 *** average of 50%of the patients visiting Korean medicine clinics were receiving Sa-am *** most prevalent indication for Sa-am acupuncture use was digestive *** patients’appetite level and digestive function were most frequently used indicators for selecting acupuncture *** prescription compositions,Jung-Gyuk formulas were more frequently used than Seung-Gyuk *** the needle along the flow of the channel or against the flow of the channel was most *** acupuncture style most frequently used in combination with Sa-am acupuncture was Ashi point *** of Sa-am acupuncture included its versatility,easy application,and good *** included the lack of rigorous education and training programs,difficulty in applying the principles for beginners,and insufficient clinical research *** In clinics where Sa-am acupuncture is available,KMDs were providing Sa-am acupuncture to about half of their *** were not using all of the tonification and sedation techniques which may be due to time constraints or simply a lack of ***-am acupuncture demonstrated high utility in clinical practice and high satisfaction based on the efficacy and *** training programs and high-quality research are needed to help expand the use of Sa-am acupuncture.

关键词： Sa-am acupuncture Traditional East Asian medicine Acupuncture education Acupoint selection

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Acupuncture ameliorates atopic dermatitis by modulating gut barrier function in a gut microbiota-dependent manner in mice

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Journal of Integrative Medicine 2024年第5期22卷 600-613页

作者： Mijung Yeom Sora Ahn Dae-Hyun Hahm Sun-Young Jang Se Hoon Jang Su-Yang Park Jae-Hwan Jang Jihan Park Ju-Young Oh In-Seon Lee Kyuseok Kim Soon-Kyeong Kwon Hi-Joon Park Acupuncture and Meridian Science Research Center College of Korean MedicineKyung Hee UniversitySeoul 02447Republic of Korea department of Physiology School of MedicineKyung Hee UniversitySeoul 02447Republic of Korea BioNanocomposite Research Center Kyung Hee UniversitySeoul 02447Republic of Korea department of Science in Korean Medicine College of Korean MedicineGraduate SchoolKyung Hee UniversitySeoul 02447Republic of Korea college of Korean Medicine Kyung Hee UniversitySeoul 02447Republic of Korea department of Ophthalmology Otorhinolaryngology and Dermatology of Korean MedicineCollege of Korean MedicineKyung Hee UniversitySeoul 02447Republic of Korea Division of Applied Life Science(BK21) Gyeongsang National UniversityJinju 52828Republic of Korea department of anatomy&Information Sciences College of Korean MedicineKyung Hee UniversitySeoul 02447Republic of Korea

Objective Atopic dermatitis(AD)is a chronic inflammatory skin disease that may be linked to changes in the gut *** has been proven to be effective in reducing AD symptoms without serious adverse events,but its underlying mechanism is not completely *** purpose of this study was to investigate whether the potential effect of acupuncture on AD is gut *** AD-like skin lesions were induced by applying MC903 topically to the cheek of the *** was done at the Gok-Ji(LI11)***-like symptoms were assessed by lesion scores,scratching behavior,and histopathological changes;intestinal barrier function was measured by fecal output,serum lipopolysaccharide levels,histopathological changes,and mRNA expression of markers involved in intestinal permeability and *** microbiota was profiled using 16S rRNA gene sequencing from fecal *** Acupuncture effectively improved chronic itch as well as the AD-like skin lesions with epidermal thickening,and also significantly altered gut microbiota structure as revealed byβ-diversity indices and analysis of *** beneficial effects were eliminated by antibiotic depletion of gut microbiota,but were reproduced in gut microbiota-depleted mice that received a fecal microbiota transplant from acupuncture-treated ***,AD mice had intestinal barrier dysfunction as indicated by increased intestinal permeability,atrophy of the mucosal structure(reduced villus height and crypt depth),decreased expression of tight junctions and mucus synthesis genes,and increased expression of inflammatory mediators in the *** attenuated these abnormalities,which was gut *** Acupuncture ameliorates AD-like phenotypes in a gut microbiota-dependent manner and some of these positive benefits are explained by modulation of the intestinal barrier,providing new perspective for non-pharmacological strategies for

关键词： Atopic dermatitis Acupuncture Gut microbiota Intestinal barrier function

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Edaravone-loaded poly(amino acid) nanogel inhibits ferroptosis for neuroprotection in cerebral ischemia injury

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Asian Journal of Pharmaceutical Sciences 2024年第2期19卷 89-101页

作者： Yunhan Zhang Zhulin Zou Shuang Liu Fangfang Chen Minglu Li Haoyang Zou Haiyan Liu Jianxun Ding Key Laboratory of Pathobiology Ministry of Education Department of AnatomyCollege of Basic Medical SciencesJilin UniversityChangchun 130061China Key Laboratory of Polymer Ecomaterials Changchun Institute of Applied ChemistryChinese Academy of SciencesChangchun 130022China department of Gastrointestinal Colorectaland Anal SurgeryChina-Japan Union Hospital of Jilin UniversityChangchun 130033China

Neurological injury caused by ischemic stroke is a major cause of permanent disability and death. The currently available neuroprotective drugs fail to achieve desired therapeutic efficacy mainly due to short circulation half-life and poor blood−brain barrier (BBB) permeability. For that, an edaravone-loaded pH/glutathione (pH/GSH) dual-responsive poly(amino acid) nanogel (NG/EDA) was developed to improve the neuroprotection of EDA. The nanogel was triggered by acidic and EDA-induced high-level GSH microenvironments, which enabled the selective and sustained release of EDA at the site of ischemic injury. NG/EDA exhibited a uniform sub-spherical morphology with a mean hydrodynamic diameter of 112.3 ± 8.2 nm. NG/EDA efficiently accumulated at the cerebral ischemic injury site of permanent middle cerebral artery occlusion (pMCAO) mice, showing an efficient BBB crossing feature. Notably, NG/EDA with 50 µM EDA significantly increased neuron survival (29.3%) following oxygen and glucose deprivation by inhibiting ferroptosis. In addition, administering NG/EDA for 7 d significantly reduced infarct volume to 22.2% ± 7.2% and decreased neurobehavioral scores from 9.0 ± 0.6 to 2.0 ± 0.8. Such a pH/GSH dual-responsive nanoplatform might provide a unique and promising modality for neuroprotection in ischemic stroke and other central nervous system diseases.

关键词： Poly(amino acid)nanogel Controlled drug delivery Inhibition of ferroptosis Neuroprotection Cerebral ischenia injury therapy

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Implications of regional identity for neural stem and progenitor cell transplantation in the injured or diseased nervous system

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Neural Regeneration Research 2024年第4期19卷 715-716页

作者： Prakruthi Amar Kumar Jennifer N.Dulin department of Biology Texas A&M UniversityCollege Station Texas A&M Institute for Neuroscience Texas A&M UniversityCollege Station

Neural stem and progenitor cell(NSPC)transpla ntation has emerged as a promising therapeutic strategy for replacing lost neuronal populations and repairing damaged neural circuits following nervous system injury and disease.A great deal of experimental work has investigated the biology of NSPC grafting in preclinical animal models;more recently.

关键词： neural system injured

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Asiaticoside ameliorates type 2 diabetes mellitus in rats by modulating carbohydrate metabolism and regulating insulin signaling

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Asian Pacific Journal of Tropical Biomedicine 2024年第9期14卷 401-409页

作者： B.Prathap V.Satyanarayanan K.Duraipandian P.Subashree department of Pharmacology Karpaga Vinayaga Institute of Medical Sciences and Research CenterMaduranthakam 603308Tamil NaduIndia department of Pharmacology SRM Medical College Hospital and Research CenterKattankulathur 603211Tamil NaduIndia department of anatomy Karpaga Vinayaga Institute of Medical Sciences and Research CenterMaduranthakam 603308Tamil NaduIndia department of Ophthalmology Karpaga Vinayaga Institute of Medical Sciences and Research CenterMaduranthakam 603308Tamil NaduIndia

Objective:To evaluate the effect of asiaticoside on streptozotocin(STZ)and nicotinamide(NAD)-induced carbohydrate metabolism abnormalities and deregulated insulin signaling pathways in ***:Asiaticoside(50 and 100 mg/kg body weight)was administered to STZ-NAD-induced diabetic rats for 45 days,and its effects on hyperglycaemic,carbohydrate metabolic,and insulin signaling pathway markers were ***:Asiaticoside increased insulin production,lowered blood glucose levels,and enhanced glycolysis by improving hexokinase activity and suppressing glucose-6-phosphatase and fructose-1,6-bisphosphatase *** in glycogen metabolism were mitigated by increasing glycogen synthase activity and gluconeogenesis was decreased by decreasing glycogen phosphorylase ***,asiaticoside upregulated the mRNA expressions of IRS-1,IRS-2,and GLUT4 in STZ-NAD-induced diabetic rats and restored the beta cell morphology to ***:Asiaticoside has the potential to ameliorate type 2 diabetes by improving glycolysis,gluconeogenesis,and insulin signaling pathways.

关键词： Asiaticoside Type 2 diabetes mellitus Metabolic disorders Carbohydrate metabolism Insulin signaling

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Ribonucleotide reductase subunit M1 blocks glucose catabolism via phosphorylation of pyruvate kinase M2 in human esophageal squamous cell cancer

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Genes & Diseases 2024年第3期11卷 69-71页

作者： Jian Yang Lingxiao Wang Hui Sun Zhenxiang Zhao Yanchuan Ma Zhen Hu Liqin Zhai Yonggang Wang Translational Medicine Research Center Shanxi Medical UniversityTaiyuanShanxi030001China department of Cell Biology and Genetics Shanxi Medical UniversityTaiyuanShanxi 030001China Key Laboratory of Cellular Physiology of the Ministry of Education Shanxi Medical UniversityTaiyuanShanxi 030001China department of Colorectal Surgery The Fifth Clinical Medical College of Shanxi Medical UniversityTaiyuanShanxi 030012China Science&Technology Information and Strategy Research Center of Shanxi TaiyuanShanxi 030006China department of Pathology Shanxi Provincial People's HospitalTaiyuanShanxi 030012China department of anatomy College of Basic MedicineShanxi Medical UniversityTaiyuanShanxi 030001China

Esophageal squamous cell cancer(EScC)is one of the malignant tumors with high morbidity and mortality all over the world.^(1) In recent years,combined chemotherapy has gradually been the effective treatment method for EscC ***,it is imperative to explore potential therapeutic targets for the treatment of *** previously reported a high-frequency amplification of pyrimidine metabolic pathway-related genes in EsCC tissues.

关键词： squamous esophageal cancer

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Comparison of the anatomy and Adaptability of Reconstructed Teeth with Natural Teeth:An Innovative Approach in Forensic Dentistry

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Journal of Forensic Science and Medicine 2024年第1期10卷 47-54页

作者： Supraja S P M Tejaswi Ravikanth Manyam Mohan Kumar Pasupuleti Swetha P Ramesh Kumar Budumuru department of Oral and Maxillofacial Pathology Vishnu Dental CollegeBhimavaramAndhra PradeshIndia Vishnu Dental college BhimavaramAndhra PradeshIndia department of Periodontics and Implantology Vishnu Dental CollegeBhimavaramAndhra PradeshIndia department of Oral Medicine and Radiology Vishnu Dental CollegeBhimavaramAndhra PradeshIndia

Background:Forensic tooth reconstruction is the technique of reconstructing the morphology of a missing tooth from the intra-alveolar morphology of dental sockets from skeletal *** and Objectives:The aim and objective of the study are to compare and investigate whether the anatomy and adaptability of reconstructed teeth simulate with the natural tooth and to investigate whether the dental materials have potential in reconstruction of *** and Methods:An in vitro experimental study was undertaken on a human *** to the Fédération Dentaire Internationale,charting will be done based on the number of teeth *** entire study will be conducted in three phases using dental *** 1 comprised preparation for negative replica,where an impression will be taken,Phase 2 comprised preparation of a positive replica or cast,and Phase 3 comprised tooth reconstruction using the flowable ***:The specimen tooth(which had been taken from its socket)and the newly constructed tooth were compared,and when the length of the newly constructed root was measured using digital vernier calipers,there was a disparity of 0.5-1 *** cone-beam computed tomography radiographs demonstrated the necessary ***:The present study demonstrated that dental information can be obtained even when teeth are absent postmortem by making an attempt to recreate the teeth using dental materials while documenting the intra-alveolar anatomy of the dental root socket.

关键词： Adaptability anatomy reconstruction teeth

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