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

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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Effectiveness of craniosacral therapy,Bowen therapy,static touch and standard exercise program on sleep quality in fibromyalgia syndrome:A randomized controlled trial

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Journal of Integrative Medicine 2024年第4期22卷 473-483页

作者： Reepa Avichal Ughreja Prem Venkatesan Dharmanand Balebail Gopalakrishna Yogesh Preet Singh Vani Lakshmi R department of Physiotherapy Manipal College of Health ProfessionsManipal Academy of Higher EducationManipal 576104KarnatakaIndia department of Rheumatology Manipal HospitalBengaluru 560052KarnatakaIndia department of Clinical Immunology and Rheumatology All India Institute of Medical SciencesBilaspur 174001Himachal PradeshIndia department of Data Science Prasanna School of Public HealthManipal Academy of Higher EducationManipal 576104KarnatakaIndia

Background:Sleep disturbance is commonly seen in fibromyalgia syndrome (FMS);however,high quality studies involving manual therapies that target FMS-linked poor sleep quality are lacking for the Indian ***:Craniosacral therapy (CST),Bowen therapy and exercises have been found to influence the autonomic nervous system,which plays a crucial role in sleep *** the paucity of evidence concerning these effects in individuals with FMS,our study tests the effectiveness of CST,Bowen therapy and a standard exercise program against static touch (the manual placebo group) on sleep quality in ***,setting,participants and intervention:A placebo-controlled randomized trial was conducted on132 FMS participants with poor sleep at a hospital in *** participants were randomly allocated to one of the four study groups,including CST,Bowen therapy,standard exercise program,and a manual placebo control group that received static ***,Bowen therapy and static touch treatments were administered in once-weekly 45-minute sessions for 12 weeks;the standard exercise group received weekly supervised exercises for 6 weeks with home exercises until 12 *** 12 weeks,all study participants performed the standard exercises at home for another 12 *** outcome measures:Sleep quality,pressure pain threshold (PPT),quality of life and fibromyalgia impact,physical function,fatigue,pain catastrophizing,kinesiophobia,and positive–negative affect were recorded at baseline,and at weeks 12 and 24 of the ***:At the end of 12 weeks,the sleep quality improved significantly in the CST group (P=0.037) and Bowen therapy group (P=0.023),and the PPT improved significantly in the Bowen therapy group(P=0.002) and the standard exercise group (P<0.001),compared to the static touch *** improvements were maintained at 24 *** between-group differences were observed for other secondary ***:CST and Bowen therapy improv

关键词： Chronic pain Complementary therapies Exercise Fibromyalgia Musculoskeletal manipulations Sleep

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Targeting the RAS/RAF/MAPK pathway for cancer therapy: from mechanism to clinical studies

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Signal Transduction and Targeted Therapy 2024年第1期9卷 173-210页

作者： Md Entaz Bahar Hyun Joon Kim Deok Ryong Kim department of biochemistry and Convergence medical sciences and Institute of medical Science Gyeongsang National UniversityCollege of MedicineJinjuSouth Korea department of Anatomy and Convergence medical sciences and Institute of medical Science Gyeongsang National UniversityCollege of MedicineJinjuSouth Korea

Metastatic dissemination of solid tumors,a leading cause of cancer-related mortality,underscores the urgent need for enhanced insights into the molecular and cellular mechanisms underlying metastasis,chemoresistance,and the mechanistic backgrounds of individuals whose cancers are prone to *** most prevalent signaling cascade governed by multi-kinase inhibitors is the mitogen-activated protein kinase(MAPK)pathway,encompassing the RAS–RAF–MAPK kinase(MEK)–extracellular signal-related kinase(ERK)*** kinase is a primary mediator of the MAPK pathway,responsible for the sequential activation of downstream targets,such as MEK and the transcription factor ERK,which control numerous cellular and physiological processes,including organism development,cell cycle control,cell proliferation and differentiation,cell survival,and *** in this signaling cascade are associated with diseases such as *** inhibitors(RAFi)combined with MEK blockers represent an FDAapproved therapeutic strategy for numerous RAF-mutant cancers,including melanoma,non-small cell lung carcinoma,and thyroid ***,the development of therapy resistance by cancer cells remains an important ***,an intracellular lysosome-dependent catabolic recycling process,plays a critical role in the development of RAFi resistance in ***,targeting RAF and autophagy could be novel treatment strategies for RAF-mutant *** this review,we delve deeper into the mechanistic insights surrounding RAF kinase signaling in tumorigenesis and ***,we explore and discuss the ongoing development of next-generation RAF inhibitors with enhanced therapeutic ***,this review sheds light on the functional interplay between RAF-targeted therapies and autophagy in cancer.

关键词： RAF insight mechanism

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Caloric restriction,Sirtuins,and cardiovascular diseases

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Chinese medical Journal 2024年第8期137卷 921-935页

作者： Ziyu Wei Bo Yang Huiyu Wang Shuangjie Lv Houzao Chen Depei Liu State Key Laboratory of Common Mechanism Research for Major Diseases Department of Biochemistry and Molecular BiologyInstitute of Basic Medical SciencesChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100005China

Caloric restriction(CR)is a well-established dietary intervention known to extend healthy lifespan and exert positive effects on aging-related diseases,including cardiovascular ***,a family of nicotinamide adenine dinucleotide(NAD^(+))-dependent histone deacetylases,have emerged as key regulators of cellular metabolism,stress responses,and the aging process,serving as energy status sensors in response to ***,the mechanism through which CR regulates Sirtuin function to ameliorate cardiovascular disease remains *** review not only provided an overview of recent research investigating the interplay between Sirtuins and CR,specifically focusing on their potential implications for cardiovascular health,but also provided a comprehensive summary of the benefits of CR for the cardiovascular system mediated directly via *** has also been shown to have considerable impact on specific metabolic organs,leading to the production of small molecules that enter systemic circulation and subsequently regulate Sirtuin activity within the cardiovascular *** direct and indirect effects of CR offer a potential mechanism for Sirtuin modulation and subsequent cardiovascular *** the interplay between CR and Sirtuins will provide new insights for the development of interventions to prevent and treat cardiovascular diseases.

关键词： Caloric restriction Sirtuins Cardiovascular diseases Healthy lifestyle Dietary

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CD87-targeted BiTE and CAR-T cells potently inhibit invasive nonfunctional pituitary adenomas

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Science China Life sciences 2024年第10期67卷 2169-2185页

作者： Yuan Ren Xinjie Bao Ming Feng Bing Xing Wei Lian Yong Yao Renzhi Wang department of Neurosurgery Peking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical College

Recently, bispecific T-cell engagers(BiTEs) and chimeric antigen receptor-modified T cells(CAR-Ts) have been shown to have high therapeutic efficacy in hematological tumors. CD87 is highly expressed in solid tumors with an oncogenic function. To assess their cytotoxic effects on invasive nonfunctioning pituitary adenomas(iNFPAs), we first examined CD87 expression and its effects on the metabolism of iNFPA cells. We generated CD87-specific BiTE and CAR/IL-12 T cells, and their cytotoxic effects on iNFPAs cells and in mouse models were determined. CD87 had high expression in i NFPA tissue and cell samples but was undetected in noncancerous brain samples. CD87×CD3 BiTE and CD87 CAR/IL-12 T-cells showed antigenic specificity and exerted satisfactory cytotoxic effects, decreasing tumor cell proliferation in vitro and reducing existing tumors in experimental mice. Overall, the above findings suggest that CD87 is a promising target for the immunotherapeutic management of iNFPAs using anti-CD87 BiTE and CD87-specific CAR/IL-12 T cells.

关键词： CD87 chimeric antigen receptor T cells invasive non-functional pituitary adenomas bispecific T cell engager Warburg effect

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Progress in the generation of spinal cord organoids over the past decade and future perspectives

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Neural Regeneration Research 2024年第5期19卷 1013-1019页

作者： Gang Zhou Siyuan Pang Yongning Li Jun Gao department of Neurosurgery Peking Union Medical College HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijingChina department of International medical Service Peking Union Medical College HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijingChina

Spinal cord organoids are three-dimensional tissues derived from stem cells that recapitulate the primary morphological and functional characteristics of the spinal cord in *** emerging bioengineering methods have led to the optimization of cell culture protocols,spinal cord organoids technology has made remarkable advancements in the past *** literature search found that current spinal cord organoids do not only dynamically simulate neural tube formation but also exhibit diverse cytoarchitecture along the dorsal-ventral and rostral-caudal ***,fused organoids that integrate motor neurons and other regionally specific organoids exhibit intricate neural circuits that allows for functional *** qualities make spinal cord organoids valuable tools for disease modeling,drug screening,and tissue *** utilizing this emergent technology,researchers have made significant progress in investigating the pathogenesis and potential therapeutic targets of spinal cord ***,at present,spinal cord organoid technology remains in its infancy and has not been widely applied in translational *** of the next generation of spinal cord organoids will depend on good manufacturing practice standards and needs to focus on diverse cell phenotypes and electrophysiological functionality evaluation.

关键词： development organoid-on-a-chip pluripotent stem cells progress spinal cord diseases spinal cord organoids vascularization

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Pancreatic ductal adenocarcinoma chemoresistance:From metabolism reprogramming to novel treatment

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Chinese medical Journal 2024年第4期137卷 408-420页

作者： Jingcheng Zhang Yutong Wang Lejunzi Wang Lei You Taiping Zhang department of General Surgery Peking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China Peking Union medical college Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China department of Anaesthesia Peking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China Clinical Immunology Centre Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China

As pancreatic cancer(PC)is highly malignant,its patients tend to develop metastasis at an early stage and show a poor response to conventional ***-line chemotherapies for PC,according to current guidelines,include fluoropyrimidine-and gemcitabine-based *** research on drug resistance has shown that biochemical metabolic aberrations in PC,especially those involving glycolysis and glutamine metabolism,are highly associated with ***,lipid metabolism is a major factor in ***,emerging compounds that target these key metabolic pathways have the potential to overcome *** review summarizes how PC develops chemoresistance through aberrations in biochemical metabolism and discusses novel critical targets and pathways within cancer metabolism for new drug research.

关键词： Pancreatic cancer Drug resistance Drug development Signal transduction

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Targeted metabolomics reveals the aberrant energy status in diabetic peripheral neuropathy and the neuroprotective mechanism of traditional Chinese medicine JinMaiTong

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Journal of Pharmaceutical Analysis 2024年第2期14卷 225-243页

作者： Bingjia Zhao Qian Zhang Yiqian He Weifang Cao Wei Song Xiaochun Liang department of Traditional Chinese Medicine Peking Union Medical College HospitalPeking Union Medical CollegeChinese Academy of Medical SciencesBeijing100730China Institute of Basic Medicine sciences Chinese Academy of Medical SciencesBeijing100005China medical Research Center Peking Union Medical College HospitalPeking Union Medical CollegeChinese Academy of Medical SciencesBeijing100730China

Diabetic peripheral neuropathy (DPN) is a common and devastating complication of diabetes, for which effective therapies are currently lacking. Disturbed energy status plays a crucial role in DPN pathogenesis. However, the integrated profile of energy metabolism, especially the central carbohydrate metabolism, remains unclear in DPN. Here, we developed a metabolomics approach by targeting 56 metabolites using high-performance ion chromatography-tandem mass spectrometry (HPIC-MS/MS) to illustrate the integrative characteristics of central carbohydrate metabolism in patients with DPN and streptozotocin-induced DPN rats. Furthermore, JinMaiTong (JMT), a traditional Chinese medicine (TCM) formula, was found to be effective for DPN, improving the peripheral neurological function and alleviating the neuropathology of DPN rats even after demyelination and axonal degeneration. JMT ameliorated DPN by regulating the aberrant energy balance and mitochondrial functions, including excessive glycolysis restoration, tricarboxylic acid cycle improvement, and increased adenosine triphosphate (ATP) generation. Bioenergetic profile was aberrant in cultured rat Schwann cells under high-glucose conditions, which was remarkably corrected by JMT treatment. In-vivo and in-vitro studies revealed that these effects of JMT were mainly attributed to the activation of adenosine monophosphate (AMP)-activated protein kinase (AMPK) and downstream peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). Our results expand the therapeutic framework for DPN and suggest the integrative modulation of energy metabolism using TCMs, such as JMT, as an effective strategy for its treatment.

关键词： Diabetic peripheral neuropathy JinMaiTong Energy metabolism Targeted metabolomics Adenosine monophosphate-activated protein kinase

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Diabetes mellitus in patients with type 1 autoimmune pancreatitis at diagnosis and after corticosteroid therapy

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Hepatobiliary & Pancreatic Diseases International 2024年第4期23卷 393-398页

作者： Mei-Zi Li Tao Guo Yun-Lu Feng Sheng-Yu Zhang Xiao-Yin Bai Xi Wu Kai Xu Ai-Ming Yang department of Gastroenterology State Key Laboratory of Complex Severe and Rare DiseasesPeking Union Medical College HospitalPeking Union Medical College and Chinese Academy of Medical SciencesBeijing 100730China department of Radiology Peking Union Medical College HospitalPeking Union Medical College and Chinese Academy of Medical SciencesBeijing 100730China

Background:A high prevalence of diabetes mellitus(DM)coexisting with autoimmune pancreatitis(AIP)is ***,evidence on the circumstances under which corticosteroid therapy(CST)for AIP improves or worsens DM is *** study aimed to demonstrate and identify predictors of DM control under the influence of ***:Patients diagnosed with type 1 AIP were enrolled from a prospectively maintained cohort and were classified into three groups according to the chronology in which AIP and DM were diagnosed:pre-existing DM(pDM),concurrent DM(cDM),and non-DM(nDM).The responses of DM to CST were assessed when corticosteroid was ceased or tapered to a maintenance dose and classified as‘improvement’and‘non-improvement’(including‘no change’and‘exacerbation’).Results:Among 101 patients with type 1 AIP,52(51.5%)patients were complicated with DM at the time of AIP diagnosis,with 36 patients in the cDM group and 16 patients in the pDM *** incidences of diffuse pancreatic swelling(72.2%)and pancreatic body/tail involvement(91.7%)were significantly higher in the cDM group than in both the pDM and nDM *** the 52 patients with DM,CST was administered in 48 *** logistic analysis identified that elevated serum gamma-glutamyl transferase(GGT)level at AIP diagnosis[odds ratio(OR)=0.032,95%confidence interval(CI):0.003-0.412,P=0.008]and pancreatic atrophy after CST(OR=0.027,95%CI:0.003-0.295,P=0.003)were negatively associated with DM control ***:Patients with diffuse pancreatic swelling and pancreatic body/tail involvement in pancreatitis tended to be complicated with cDM at AIP *** exerted a beneficial effect on the clinical course of DM in nearly half of the AIP patients complicated with DM at diagnosis,particularly in those without elevated serum GGT levels at diagnosis and who did not experience pancreatic atrophy after CST.

关键词： Type 1 autoimmune pancreatitis Diabetes mellitus Corticosteroid therapy Predictive factor Pancreatic atrophy

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Multidisciplinary approach toward enhanced recovery after surgery for total knee arthroplasty improves outcomes

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World Journal of Clinical Cases 2024年第9期12卷 1549-1554页

作者： Deb Sanjay Nag Amlan Swain Seelora Sahu Ayaskant Sahoo Gunjan Wadhwa department of Anaesthesiology Tata Main HospitalJamshedpur 831001India department of Anaesthesiology Manipal Tata Medical CollegeJamshedpur 831001India

Knee osteoarthritis is a degenerative disorder of the knee,which leads to joint pain,stiffness,and inactivity and significantly affects the quality of *** an increased prevalence of obesity and greater life expectancies,total knee arthroplasty(TKA)is now one of the major arthroplasty surgeries performed for knee *** enhanced recovery after surgery(ERAS)was introduced in TKA,clinical outcomes were enhanced and the economic burden on the healthcare system was *** is an evidence-based scientific protocol aimed at ameliorating the surgical stress *** aims to enhance the recovery phase,which encompasses multidisciplinary strategies at every step of perioperative care,including the rehabilitation *** of ERAS in TKA aids in reducing the length of hospital stay,improving pain management,reducing perioperative complications,and enhancing patient *** collaboration,integrating the expertise of anesthesiologists,orthopedic surgeons,nursing personnel,and other healthcare professionals,is the cornerstone of ERAS in patients undergoing TKA.

关键词： Arthroplasty Replacement Knee Recovery of function Anesthesia Care Nursing

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