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Liver Characterization of a Cohort of Alpha-1 Antitrypsin Deficiency Patients with and without Lung Disease

Journal of clinical and Translational Hepatology 2024年第10期12卷 845-856页

作者： Naweed Mohammad Regina Oshins Tongjun Gu Virginia Clark Jorge Lascano Naziheh Assarzadegan George Marek Mark Brantly Nazli Khodayari Division of Pulmonary Critical Care and Sleep MedicineCollege of MedicineUniversity of FloridaGainesvilleFLUSA Interdisciplinary Center for Biotechnology Research Bioinformatics CoreUniversity of FloridaGainesvilleFLUSA Division of Gastroenterology Hepatology and NutritionCollege of MedicineUniversity of FloridaGainesvilleFLUSA Division of Pathology Immunologyand Laboratory MedicineCollege of MedicineUniversity of FloridaGainesvilleFLUSA Division of Gastroenterology and Hepatology Mayo ClinicRochesterMNUSA

Background and Aims:Alpha-1 antitrypsin deficiency(AATD)is a genetic disorder characterized by the misfolding and accumulation of the mutant variant of alpha-1 antitrypsin(AAT)within hepatocytes,which limits its access to the circulation and exposes the lungs to protease-mediated tissue *** results in progressive liver disease secondary to AAT polymerization and accumulation,and chronic obstructive pulmonary disease(COPD)due to deficient levels of AAT within the *** goal was to characterize the unique effects of COPD secondary to AATD on liver disease and gene ***:A subcohort of AATD individuals with COPD(n=33)and AATD individuals without COPD(n=14)were evaluated in this study from our previously reported cross-sectional *** used immunohistochemistry to assess the AATD liver phenotype,and RNA sequencing to explore liver *** observed a distinct transcriptomic profile in liver tissues from AATD individuals with COPD compared to those ***:A total of 339 genes were differentially *** pathways related to fibrosis,extracellular matrix remodeling,collagen deposition,hepatocellular damage,and inflammation were significantly upregulated in the livers of AATD individuals with *** analysis also revealed higher levels of fibrosis and hepatocellular damage in these ***:Our data supports a relationship between the development of COPD and liver disease in AATD and introduces genes and pathways that may play a role in AATD liver disease when COPD is *** believe addressing lung impairment and airway inflammation may be an approach to managing AATD-related liver disease.

关键词： Alpha-1 antitrypsin deficiency Chronic obstructive pulmonary disease Liver fibrosis Liver biopsy Liver histology Transcriptomics

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Resveratrol as an Anti-inflammatory Agent in Coronary Artery Disease:A Systematic Review, Meta-Analysis and Meta-Regression

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Chinese Journal of Integrative medicine 2024年第10期30卷 927-937页

作者： Vito A.Damay Ignatius Ivan Department of Cardiovascular medicine Universitas Pelita Harapan Jakarta Varices clinic

Background: Resveratrol is a non-flavonoid polyphenol that shows promise in reducing proinflammatory factors and maintaining endothelial function, which hints at its potential role in slowing atherosclerosis and preventing acute coronary events. Objective: To study the cardioprotective effects of resveratrol on inflammatory mediators and endothelial function in patients with coronary artery disease(CAD). Methods: A thorough search was conducted in databases(Cochrane Library, Pro Quest, Pub Med, LILACS, science Direct, Springer, Taylor&Francis, CNKI, Wanfang, and Weipu) until September 24, 2023. The vasopro-inflammatory mediators, endothelial function and outcomes related to cardiovascular events were observed. Titles and abstracts were assessed, and bias was evaluated with Cochrane Ro B 2.0. Heterogeneity of results was explored by metaregression, certainty of evidence was assessed by the GRADE system, and conclusive evidence was enhanced by trial sequence analysis. Results: Ten randomized controlled trials and 3 animal studies investigated resveratrol's impact on inflammatory mediators and endothelial function. In primary prevention studies, meta-analysis showed a significant reduction(95% CI: –0.73 to –0.20; P=0.0005) in tumor necrosis factor-α(TNF-α) expression with resveratrol, demonstrating a dose-dependent relationship. No significant difference was observed in interleukin-6(IL-6) expression with P=0.58 for primary prevention and P=0.57 for secondary prevention. Vascular endothelial nitric oxide synthase(e NOS) expression was significantly increased after resveratrol pre-treatment following CAD events. Secondary prevention studies yielded no significant results; however, meta-regression identified associations between age, hypertension, and lower doses with the extent of TNF-α alterations. High certainty of evidence supported TNF-α reduction, while evidence for IL-6 reduction and e NOS elevation was deemed low. Conclusions: Resveratrol reduces TNF-α in individ

关键词： anti-inflammation coronary artery disease nitric oxide resveratrol systematic review

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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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The endogenous antioxidant ability of royal jelly in Drosophila is independent of Keap1/Nrf2 by activating oxidoreductase activity

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Insect science 2024年第2期31卷 503-523页

作者： Dongjing Wen Jiayu Xie Yao Yuan Lirong Shen Yufeng Yang Wenfeng Chen Institute of Life sciences College of Biological Science and EngineeringFuzhou UniversityFuzhouChina School of medicine Chongqing UniversityChongqingChina college of Biosystems Engineering and Food science Zhejiang UniversityHangzhouChina

Royal jelly(RJ)is a biologically active substance secreted by the hypopharyngeal and mandibular glands of worker *** is widely claimed that RJ reduces oxidative ***,the antioxidant activity of RJ has mostly been determined by in vitro chemical detection methods or by external administration drugs that cause oxidative *** RJ can clear the endogenous production of reactive oxygen species(ROS)in cells remains largely ***,we systematically investigated the antioxidant properties of RJ using several endogenous oxidative stress models of *** found that RJ enhanced sleep quality of aging Drosophila,which is decreased due to an increase of oxidative damage with *** supplementation improved survival and suppressed ROS levels in gut cells of flies upon exposure to hydrogen peroxide or to the neurotoxic agent ***,RJ supplementation moderated levels of ROS in endogenous gut cells and extended lifespan after exposure of flies to heat *** deprivation leads to accumulation of ROS in the gut cells,and RJ attenuated the consequences of oxidative stress caused by sleep loss and prolonged ***,RJ prevented cell oxidative damage caused by heat stress or sleep deprivation,with the antioxidant activity in vivo independent of Keap1/Nrf2 *** supplementation activated oxidoreductase activity in the guts of flies,suggesting its ability to inhibit endogenous oxidative stress and maintain health,possibly in humans.

关键词： antioxidant biological oxidations Drosophila oxidative stress royal jelly sleep loss

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A novel mechanism of PHB2-mediated mitophagy participating in the development of Parkinson's disease

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Neural Regeneration Research 2024年第8期19卷 1828-1834页

作者： Yongjiang Zhang Shiyi Yin Run Song Xiaoyi Lai Mengmeng Shen Jiannan Wu Junqiang Yan Key Laboratory of Neuromolecular Biology The First Affiliated HospitalCollege of Clinical Medicine of Henan University of Science and TechnologyLuoyangHenan ProvinceChina Department of Neurology The First Affiliated HospitalCollege of Clinical Medicine of Henan University of Science and TechnologyLuoyangHenan ProvinceChina

Endoplasmic reticulum stress and mitochondrial dysfunction play important roles in Parkinson s disease,but the regulato ry mechanism remains ***-2(PHB2)is a newly discove red autophagy receptor in the mitochondrial inner membrane,and its role in Parkinson’s disease remains *** kinase R(PKR)-like endoplasmic reticulum kinase(PERK)is a factor that regulates cell fate during endoplasmic reticulum *** is regulated by PERK and is a target of the unfolded protein *** is unclear whether PERK regulates PHB2-mediated mitophagy thro ugh *** this study,we established a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced mouse model of Parkinson’s *** used adeno-associated virus to knockdown PHB2 *** res ults showed that loss of dopaminergic neurons and motor deficits were aggravated in the MPTP-induced mouse model of Parkinson’s *** rexpression of PHB2 inhibited these *** also established a 1-methyl-4-phenylpyridine(MPP+)-induced SH-SY5Y cell model of Parkinson’s *** found that ove rexpression of Parkin increased co-localization of PHB2 and microtubule-associated protein 1 light chain 3,and promoted *** addition,MPP+regulated Parkin involvement in PHB2-mediated mitophagy through phosphorylation of *** findings suggest that PHB2 participates in the development of Parkinson’s disease by intera cting with endoplasmic reticulum stress and Parkin.

关键词： endoplasmic reticulum dopaminergic neuron microtubule-associated protein 1 light chain 3 mitophagy oxidative stress Parkin Parkinson’s disease PKR-like endoplasmic reticulum kinase reactive oxygen species prohibitin-2

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Delphi study for developing a checklist of adverse events associated with acupotomy

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Journal of Integrative medicine 2024年第5期22卷 579-587页

作者： Hyungsun Jun Haebeom Lee Sang-Hoon Yoon Chan-Young Kwon Damin Jeon Jun-Hwan Lee Jungtae Leem Department of Diagnostics College of Korean MedicineWonkwang UniversityIksan 54538Republic of Korea Days Inc. Seoul 06247Republic of Korea Chung-Yeon Korean medicine clinic Seoul 06224Republic of Korea Department of Oriental Neuropsychiatry Dong-Eui University College of Korean MedicineBusan 47227Republic of Korea Chonnam National University Hwasun Hospital Hwasun 58128Republic of Korea KM science Research Division Korea Institute of Oriental MedicineDaejeon 34054Republic of Korea Department of Korean Convergence Medical science KIOM SchoolUniversity of Science&Technology(UST)Daejeon 34054Republic of Korea Department of Physical medicine and Rehabilitation Spaulding Rehabilitation HospitalHarvard Medical SchoolBostonMA 02115USA Research Center of Traditional Korean medicine College of Korean MedicineWonkwang UniversityIksan 54538Republic of Korea

Background Acupotomy,a more invasive procedure than acupuncture,involves the use of a thicker needle with an integrated knife at the tip,necessitating safety *** aimed to define relevant adverse events(AEs)and create a standardized form of the ACUPOtomy-related AEs CHECKlist(ACUPOCHECK).Methods Before conducting the Delphi process,a systematic review and pilot prospective study were conducted to gather information on previously reported *** these data,pilot versions of the ACUPOCHECK and Delphi questionnaires were *** Delphi questionnaire involved selecting types of AE for inclusion,establishing separate criteria for acupotomy-related AEs,and achieving a consensus on AE *** Korean doctors with experience in acupotomy or AE research were recruited to participate in each Delphi *** was considered to have been reached if the critical value for the content validity ratio met or exceeded *** The final ACUPOCHECK was developed using four rounds of the Delphi method and one face-to-face consensus *** included 12 local AEs(pain,hemorrhage,bruise,hematoma,edema,pruritus,rash,infection,nerve damage,dysesthesia,movement impairment,and pneumothorax)and 14 systemic AEs(disease aggravation,needle fatigue,sleepiness,procedural nausea,procedural vomiting,procedural headache,procedural dizziness,sweating,procedural shock,syncope,dyspnea,procedural pain,sleep disorder,and postprocedural infection).Separate criteria were established for pain,hemorrhage and bruising:pain was defined as pain that occurrs during daily activities and persists for longer than 72 h,hemorrhage as bleeding that continues for≥3 min despite pressure application,and bruising as having a bruise with a diameter of≥3 ***-ended descriptions were allowed for AEs not covered by the checklist,and severity and causality were assessed using the Common Terminology Criteria for Adverse Events and modified World Health Organization-Uppsala Monitoring C

关键词： Acupotomy Delphi technique Patient safety Safety management Adverse event

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Involvement of the ABA-and H_(2)O_(2)-Mediated Ascorbate-Glutathione Cycle in the Drought Stress Responses of Wheat Roots

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Phyton-International Journal of Experimental Botany 2024年第2期93卷 329-342页

作者： Mengyuan Li Zhongye Gao Lina Jiang Leishan Chen Jianhui Ma college of Life science Henan Normal UniversityXinxiang453007China School of Life science and Basic medicine Xinxiang UniversityXinxiang453003China

Abscisic acid(ABA),hydrogen peroxide(H_(2)O_(2)) and ascorbate(AsA)–glutathione(GSH)cycle are widely known for their participation in various ***,the relationship between ABA and H_(2)O_(2) levels and the AsA–GSH cycle under drought stress in wheat has not been *** this study,a hydroponic experiment was conducted in wheat seedlings subjected to 15%polyethylene glycol(PEG)6000–induced *** stress caused the rapid accumulation of endogenous ABA and H_(2)O_(2) and significantly decreased the number of root tips compared with the *** application of ABA significantly increased the number of root tips,whereas the application of H_(2)O_(2) markedly reduced the number of root tips,compared with that under 15%*** addition,drought stress markedly increased the DHA,GSH and GSSG levels,but decreased the AsA levels,AsA/DHA and GSH/GSSG ratios compared with those in the *** activities of the four enzymes in the AsA–GSH cycle were also markedly increased under drought stress,including glutathione reductase(GR),ascorbate peroxidase(APX),monodehydroascorbate reductase(MDHAR)and dehydroascorbate reductase(DHAR),compared with those in the ***,the application of an ABA inhibitor significantly inhibited GR,DHAR and APX activities,whereas the application of an H_(2)O_(2) inhibitor significantly inhibited DHAR and MDHAR ***,the application of ABA inhibitor significantly promoted the increases of H_(2)O_(2) and the application of H_(2)O_(2) inhibitor significantly blocked the increases of ABA,compared with those under 15% *** together,the results indicated that ABA and H_(2)O_(2) probably interact under drought stress in wheat;and both of them can mediate drought stress by modulating the enzymes in AsA–GSH cycle,where ABA acts as the main regulator of GR,DHAR,and APX activities,and H_(2)O_(2) acts as the main regulator of DHAR and MDHAR activities.

关键词： ABA H_(2)O_(2) AsA-GSH cycle drought stress wheat roots

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Damage on intestinal barrier function and microbial detoxification of deoxynivalenol:A review

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Journal of Integrative Agriculture 2024年第8期23卷 2507-2524页

作者： Jia Chen Xinran Zhang Ziqi He Dongwei Xiong Miao Long Key Laboratory of Livestock Infectious Diseases Ministry of Education/College of Animal Science and Veterinary Medicine ShenyangAgricultural UniversityShenyang 110866China

Deoxynivalenol(DON)is a mycotoxin that is produced by various species of Fusarium and is ubiquitous in food and *** low concentrations,it can cause metabolic disorders in animals and humans and,at high concentrations,it can lead to pathological changes in the *** impact of DON on human/animal health and animal productivity has thus attracted a great deal of attention around the *** causes severe damage to the intestine,including compromised intestinal barrier,mucosal damage,weakened immune function,and alterations in gut microbiota *** effects exacerbate intestinal infections and inflammation in livestock and poultry,posing adverse effects on overall ***,research into biological methods for DON detoxification is a crucial avenue for future *** includes the utilization of adsorption,enzymatic degradation,and other biological approaches to mitigate DON's impact,offering new strategies for prevention and treatment of DON-induced *** research will focus on identifying highly efficient detoxifying microorganisms or enzymes to reduce DON levels in food and feed,thereby mitigating its risks to both animals and human health.

关键词： deoxynivalenol(DON) intestinal barrier function mucus barrier immune function flora composition biological detoxification

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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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D-Psicose intake exacerbates dextran sulfate sodium-induced colitis in mice through alteration in the gut microbiota and dysfunction of mucosal barrier

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Food science and Human Wellness 2024年第1期13卷 173-182页

作者： Xuejiao Zhang Ang Li Yuanyifei Wang Jin Wang Bowei Zhang Yan Zhang Jingmin Liu Shuo Wang Tianjin Key Laboratory of Food science and Health School of MedicineNankai UniversityTianjin 300072China college of Food science and Technology Hebei Agricultural UniversityBaoding 071001China

D-Psicose,as a low-calorie rare sugar,has attracted a lot of attention in recent years for alternating to *** anti-obesity effect of D-psicose has been extensively confirmed in previous studies,however,the impact of D-psicose on colitis remains ***,we firstly evaluated the effect of the D-psicose prophylactic intervention on dextran sulfate sodium-induced colitis in C57BL/6 *** pathological symptoms,inflammatory cytokines levels,gut microbiota composition,short chain fatty acids(SCFAs)production and colonic barrier integrity were comprehensively *** results confirmed that D-psicose intervention aggravated colitis,characterized by the exacerbation of colon shortening,increase of colonic inflammatory infiltration,and marked exaltation of disease activity indices and IL-6,IL-1βand TNF-α***,the dysfunction of gut microbiota was identified in the psicose *** abundance of pro-inflammatory bacteria Lachnospiraceae_NK4A136_group was significantly up-regulated while the abundance of probiotics Akkermansia and Lactobacillus were significantly down-regulated in the psicose group compared to the model ***,the production of SCFAs was suppressed in the psicose group,accompanied by a decrease in the level of mucin 2(Muc-2).Collectively,the underlying mechanism of the exacerbation of colitis by D-psicose intervention might be attributed to microbiota dysfunction accompanied by the reduction of SCFAs,which leads to the damage of the mucosal barrier and the intensifi cation of inflammatory invasion.

关键词： D-Psicose Colitis Gut microbiota Short chain fatty acids Mucin 2

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