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Alkaline sphingomyelinase deficiency impairs intestinal mucosal barrier integrity and reduces antioxidant capacity in dextran sulfate sodium-induced colitis

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World Journal of Gastroenterology 2024年第10期30卷 1405-1419页

作者： Ye Tian Xin Li Xu Wang Si-Ting Pei Hong-Xin Pan Yu-Qi Cheng Yi-Chen Li Wen-Ting Cao Jin-Dong Ding Petersen Ping Zhang International School of Public health and one health Hainan Medical UniversityHaikou 571199Hainan ProvinceChina Medical Laboratory Science and Technology College Harbin Medical University-Daqing CampusDaqing 163000Heilongjiang ProvinceChina Department of Laboratory Diagnosis Qiqihar Tuberculosis Control CenterQiqihar 161000Heilongjiang ProvinceChina Department of Public health University of CopenhagenCopenhagen 1353Denmark Department of Public health University of Southern DenmarkOdense 5000Denmark

BACKGROUND Ulcerative colitis is a chronic inflammatory disease of the colon with an unknown etiology.Alkaline sphingomyelinase(alk-SMase)is specifically expressed by intestinal epithelial cells,and has been reported to play an anti-inflammatory role.However,the underlying mechanism is still unclear.AIM To explore the mechanism of alk-SMase anti-inflammatory effects on intestinal barrier function and oxidative stress in dextran sulfate sodium(DSS)-induced colitis.METHODS Mice were administered 3%DSS drinking water,and disease activity index was determined to evaluate the status of colitis.Intestinal permeability was evaluated by gavage administration of fluorescein isothiocyanate dextran,and bacterial translocation was evaluated by measuring serum lipopolysaccharide.Intestinal epithelial cell ultrastructure was observed by electron microscopy.Western blotting and quantitative real-time reverse transcription-polymerase chain reaction were used to detect the expression of intestinal barrier proteins and mRNA,respectively.Serum oxidant and antioxidant marker levels were analyzed using commercial kits to assess oxidative stress levels.RESULTS Compared to wild-type(WT)mice,inflammation and intestinal permeability in alk-SMase knockout(KO)mice were more severe beginning 4 d after DSS induction.The mRNA and protein levels of intestinal barrier proteins,including zonula occludens-1,occludin,claudin-3,claudin-5,claudin-8,mucin 2,and secretory immunoglobulin A,were significantly reduced on 4 d after DSS treatment.Ultrastructural observations revealed progressive damage to the tight junctions of intestinal epithelial cells.Furthermore,by day 4,mitochondria appeared swollen and degenerated.Additionally,compared to WT mice,serum malondialdehyde levels in KO mice were higher,and the antioxidant capacity was significantly lower.The expression of the transcription factor nuclear factor erythroid 2-related factor 2(Nrf2)in the colonic mucosal tissue of KO mice was significantly decreased after DSS treatment.mRNA levels of Nrf2-re

关键词： Alkaline sphingomyelinase Intestinal mucosal barrier Antioxidant capacity Dextran sulfate sodium-induced colitis nuclear factor erythroid 2-related factor 2

JW-1-283 inhibits melanoma tumor growth via stabilization of the p53 pathway

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Genes & Diseases 2024年第3期11卷 18-21页

作者： Yang Xie Ruida Hou Kelli LHartman Jianxiong Jiang Zhongzhi Wu Wei Li Drug Discovery center College of PharmacyUniversity of Tennessee Health Science CenterMemphisTN38163USA

Melanoma is a lethal skin malignancy and the fifth most diagnosed cancer in the United States.1 Currently,for unresectable melanoma,the recommended treatment options include checkpoint inhibitor immunotherapy targeting programmed cell death 1(PD-1),and inhibitors targeting the mitogen-activated protein kinase(MAPK)pathway.However,the response rate may vary among the patients,and therefore demanding the development of novel treatment strategies.Tumor suppressor TP53has been suggested as one of the critical regulators mediating the aggressiveness and progression of melanoma.

关键词： melanoma suppressor death

Fermented Lentinus edodes extract containingα-glucan ameliorates concanavalin A-induced autoimmune hepatitis in mice

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Food Science and Human Wellness 2024年第4期13卷 2102-2115页

作者： Xin Hu Dan Cheng Yingxia Zhang Po Li Xiaoping Wu Junsheng Fu College of Life Sciences Fujian Agriculture and Forestry UniversityFuzhou 350002China Mycological Research center Fujian Agriculture and Forestry UniversityFuzhou 350002China Shanghai Lithy one-health Group Technology Co. Ltd.Shanghai 200235China

Autoimmune hepatitis(AIH)is a chronic inflammatory liver disease that threatens human health worldwide.The aim of this study was to detect the protective effect of a fermented Lentinus edodes extract containingα-glucan(FLA),in a concanavalin A(Con A)-induced AIH mouse model and to determine the underlying liver-protective mechanism.The results showed that compared with the model group,the level of proinflammatory cytokines in serum of FLA pretreated mice was significantly decreased,and the degree of inflammatory cell infiltration in liver,thymus and spleen was significantly reduced.Quantitative polymerase chain reaction,immunohistochemistry,and Western blotting showed that FLA pre-treatment inhibited the Con A-induced apoptosis of hepatocytes by down-regulating the expression of BAX and up-regulating the expression of BCL-2.Further research found that FLA may improve liver injury in mice by activating NRF2 signaling pathway and inhibiting TRAF6/NF-κB signaling pathway.Thus,FLA may improve liver injury in mice by shifting gut microbial composition to reduce the release of inflammatory cytokines in the serum and prevent the necrosis of hepatocytes.Up-regulation of NRF2 signaling pathway,down-regulation of TRAF6/NF-κB signaling pathway,and an increase in the relative abundance of Lactobacillus_johnsonii and Ligilactobacillus_murinus play a protective role in liver.

关键词： Autoimmune hepatitis Concanavalin A Lentinus edodes TRAF6/NF-κB NRF2

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health benefits from the rapid reduction in ambient exposure to air pollutants after China's clean air actions:progress in efficacy and geographic equality

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National Science Review 2024年第2期11卷 103-113页

作者： Tao Xue Ruohan Wang Meng Wang Yanying Wang Dan Tong Xia Meng Conghong Huang Siqi Ai Fangzhou Li Jingyuan Cao Mingkun Tong Xueqiu Ni Hengyi Liu Jianyu Deng Hong Lu Wei Wan Jicheng Gong Shiqiu Zhang Tong Zhu Clean Air Asia Institute of Reproductive and Child health National Health Commission Key Laboratory of Reproductive Health/Department of Epidemiology and Biostatistics Ministry of Education Key Laboratory of Epidemiology of Major Diseases(PKU) School of Public Health Peking University Health Science Centre State Environmental Protection Key Laboratory of Atmospheric Exposure and Health Risk Management and Center for Environment and Health Peking University Advanced Institute of Information Technology Peking University Department of Epidemiology and Environmental health School of Public Health and Health ProfessionsUniversity at Buffalo State Key Joint Laboratory of Environment Simulation and Pollution Control College of Environmental Sciences and EngineeringPeking University Department of Earth System Science Tsinghua University School of Public health Key Laboratory of Public Health Safety of the Ministry of Education and Key Laboratory of Health Technology Assessment of the Ministry of HealthFudan University College of Land Management Nanjing Agricultural University National&Local Joint Engineering Research Center for Rural Land Resources Use and Consolidation

Clean air actions （CAAs） in China have been linked to considerable benefits in public health.However,whether the beneficial effects of CAAs are equally distributed geographically is unknown.Using high-resolution maps of the distributions of major air pollutants (fine particulate matter[PM2.5]and ozone[O3]) and population,we aimed to track spatiotemporal changes in health impacts from,and geographic inequality embedded in,the reduced exposures to PM2.5and O3from 2013 to 2020.We used a method established by the Global Burden of Diseases Study.By analyzing the changes in loss of life expectancy（LLE） attributable to PM2.5and O3,we calculated the gain of life expectancy （GLE） to quantify the health benefits of the air-quality improvement.Finally,we assessed the geographic inequality embedded in the GLE using the Gini index （GI）.Based on risk assessments of PM2.5and O3,during the first stage of CAAs（2013 to 2017）,the mean GLE was 1.87 months.Half of the sum of the GLE was disproportionally distributed in about one quarter of the population exposed （GI 0.44）.During the second stage of CAAs（2017 to 2020）,the mean GLE increased to 3.94 months and geographic inequality decreased （GI 0.18）.According to our assessments,CAAs were enhanced,from the first to second stages,in terms of not only preventing premature mortality but also ameliorating health inequalities.The enhancements were related to increased sensitivity to the health effects of air pollution and synergic control of PM2.5and O3levels.Our findings will contribute to optimizing future CAAs.

关键词： clean air action public health inequality fine particulate matter ozone

Natural variables separate the endemic areas of Clonorchis sinensis and Opisthorchis viverrini along a continuous, straight zone in Southeast Asia

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贫困所致传染病(英文) 2024年第2期13卷 1-13页

作者： Zheng Jin-Xin Zhu Hui-Hui Xia Shang Qian Men-Bao Nguyen Hung Manh Sripa Banchob Sayasone Somphou Khieu Virak Bergquist Robert Zhou Xiao-Nong School of Global health Chinese Center for Tropical Diseases Research Shanghai Jiao Tong University School of Medicine Shanghai China one health center Shanghai Jiao Tong University The University of Edinburgh Shanghai China National Institute of Parasitic Diseases at Chinese center for Disease Control and Prevention (Chinese center for Tropical Diseases Research) NHC Key Laboratory of Parasites and Vectors Biology WHO Collaborating Centre for Tropical Diseases National Center for International Research on Tropical Diseases Shanghai China Institute of Ecology and Biological Resources Graduate University of Science and Technology Vietnam Academy of Science and Technology Hoang Quoc Viet Street Hanoi Vietnam WHO Collaborating Centre for Research and Control of Opisthorchiasis (Southeast Asian Liver Fluke Disease) Tropical Disease Research Laboratory Department of Tropical Medicine Faculty of Medicine Khon Kaen University Mittraparb Road Khon Kaen Thailand Lao Tropical and Public health Institute Ministry of Health Vientiane Lao PDR National Centre for Parasitology Entomology and Malaria Control Ministry of Health Phnom Penh Cambodia Ingerod Brastad Sweden (formerly at the UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases) World Health Organization Geneva Switzerland

Background Clonorchiasis and opisthorchiasis, caused by the liver flukesClonorchis sinensis andOpisthorchis viverrini respectively, represent significant neglected tropical diseases (NTDs) in Asia. The co-existence of these pathogens in overlapping regions complicates effective disease control strategies. This study aimed to clarify the distribution and interaction of these diseases within Southeast Asia.Methods We systematically collated occurrence records of human clonorchiasis (n = 1809) and opisthorchiasis (n = 731) across the Southeast Asia countries. Utilizing species distribution models incorporating environmental and climatic data, coupled machine learning algorithms with boosted regression trees, we predicted and distinguished endemic areas for each fluke species. Machine learning techniques, including geospatial analysis, were employed to delineate the boundaries between these flukes.Results Our analysis revealed that the endemic range ofC. sinensis andO. viverrini in Southeast Asia primarily spans across part of China, Vietnam, Thailand, Laos, and Cambodia. During the period from 2000 to 2018, we identifiedC. sinensis infections in 84 distinct locations, predominantly in southern China (Guangxi Zhuang Autonomous Region) and northern Vietnam. In a stark contrast,O. viverrini was more widely distributed, with infections documented in 721 locations across Thailand, Laos, Cambodia, and Vietnam. Critical environmental determinants were quantitatively analyzed, revealing annual mean temperatures ranging between 14 and 20 °C in clonorchiasis-endemic areas and 24–30 °C in opisthorchiasis regions (P one, demonstrating a clear separation between the endemic areas of these two liver flukes with AUC from 0.9 to1. The study in Vietnam delineates the coexistence and geographical boundaries ofC. sinensis andO. viverrini, revealing distinct endemic zones and a transitional area where both liver fluke species overlap.Conclusions Our findings

关键词： Liver fluke Clonorchiasis Opisthorchiasis Clonorchis sinensis Opisthorchis viverrine Southeast Asia Machine learning Ecological study

Detection of a reassortant swine H1N2 influenza A virus from pigs in Hong Kong

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Virologica Sinica 2024年第2期39卷 343-346页

作者： Guoqian Gu Congnuan Liu Song Hao Lee Lewis Sze Chun Choi Michael T.Wilson Dirk U.Pfeiffer Yun Young Go Department of Infectious Diseases and Public health Jockey Club College of Veterinary Medicine and Life SciencesCity University of Hong KongHong Kong SARChina center for Applied one health Research and Policy Advice Jockey Club College of Veterinary Medicine and Life SciencesCity University of Hong KongHong Kong SARChina College of Veterinary Medicine Konkuk UniversitySeoul143-701Republic of Korea

Dear Editor,Influenza A viruses(IAVs)are responsible for significant respiratory illnesses in humans and a broad range of animal species.Repeated outbreaks and the rapid spread of genetically and antigenically distinct IAVs represent a considerable challenge for swine production.Pigs are susceptible to avian and human IAV infections and are considered“mixing vessels”where human,avian,and swine IAVs can recombine and generate novel reassortant influenza viruses with pandemic potential(Vincent et al.,2014).

关键词： swine influenza mixing

Exosome-encapsulated lncRNA HOTAIRM1 contributes to PM_(2.5)-aggravated COPD airway remodeling by enhancing myofibroblast differentiation

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Science China(Life Sciences) 2024年第5期67卷 970-985页

作者： Huaqi Guo Luo Fei Hengyi Yu Yan Li Yan Feng Shaowei Wu Yan Wang The Ninth People’s Hospital of Shanghai Jiao Tong University School of Medicine Shanghai 200011China School of Public health Shanghai Jiao Tong University School of MedicineShanghai 200020China Department of Occupational and Environmental health Sciences School of Public HealthXi’an Jiao Tong University Health Science CenterXi’an 710049China

Emphysema,myofibroblast accumulation and airway remodeling can occur in the lungs due to exposure to atmospheric pollution,especially fine particulate matter(PM_(2.5)),leading to chronic obstructive pulmonary disease(COPD).Specifically,bronchial epithelium-fibroblast communication participates in airway remodeling,which results in COPD.An increasing number of studies are now being conducted on the role of exosome-mediated cell-cell communication in disease pathogenesis.Here,we investigated whether exosomes generated from bronchial epithelial cells could deliver information to normal stromal fibroblasts and provoke cellular responses,resulting in airway obstruction in COPD.We studied the mechanism of exosome-mediated intercellular communication between human bronchial epithelial(HBE) cells and primary lung fibroblasts(pLFs).We found that PM_(2.5)-induced HBE-derived exosomes promoted myofibroblast differentiation in pLFs.Then,the exosomal lncRNA expression profiles derived from PM_(2.5)-treated HBE cells and nontreated HBE cells were investigated using an Agilent Human LncRNA Array.Combining coculture assays and direct exosome treatment,we found that HBE cell-derived exosomal HOTAIRM1 facilitated the myofibroblast differentiation of pLFs.Surprisingly,we discovered that exosomal HOTAIRM1 enhanced p LF proliferation to secrete excessive collagen secretion,leading to airway obstruction by stimulating the TGF-β/SMAD3 signaling pathway.Significantly,PM_(2.5)reduced FEV1/FVC and FEV1 and increased the level of serum exosomal HOTAIRM1 in healthy people;moreover,serum exosomal HOTAIRM1 was associated with PM_(2.5)-related reductions in FEV1/FVC and FVC.These findings show that PM_(2.5)triggers alterations in exosome components and clarify that one of the paracrine mediators of myofibroblast differentiation is bronchial epithelial cell-derived HOTAIRM1,which has the potential to be an effective prevention and therapeutic target for PM_(2.5)-induced COPD.

关键词： PM2.5 exosomal lncRNAs HOTAIRM1 chronic obstructive pulmonary disease

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Distribution of licensed acupuncturists and educational institutions in the United States at the start of 2023,during the late stage of the COVID-19 pandemic

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Journal of Integrative Medicine 2024年第4期22卷 379-384页

作者： Arthur Yin Fan De-guang He Anu Sangraula Sarah Faggert Alemi Amy Matecki American Traditional Chinese Medicine Association McLean center for Complementary and Alternative Medicine New England School of Acupuncture Massachusetts College of Pharmacy and Health Sciences Lombardi Comprehensive Cancer center Cancer Prevention and Control Program Georgetown University Eastern Roots Wellness PLC Sutter health Alta Bates Summit Medical Center

This study was conducted to identify the number and density of active licensed acupuncturists(LAcs), as well as the number of accredited schools in acupuncture and Oriental medicine(AOM), as of January 1,2023, in the United States(U.S.). The number of active LAcs as of January 1, 2023 was 34,524, potentially33,364 after removing license duplication in multiple states, among which the largest three states were California(with 7317 LAcs [21.19% of the total]), New York(5024 [14.55%]) and Florida(2644 [7.66%]).The total number of LAcs decreased by 8.87% from 2018, and fell short of our projected number of LAcs in 2023 by 9037, or 20.75%. The overall LAc density in the U.S.Dmeasured as the number of LAcs per 100,000 populationDwas 10.36, less than in 2018. There were 56 active, accredited AOM schools which offered a total of 147 programs(121 at the level necessary for licensing [entry-level], 12 for an advanced practicing degree [advanced-level], and 14 for certifications). Broken down further, offerings included 50 master's degrees in acupuncture, 40 master's degrees in Oriental medicine, 31 entry-level doctorate degrees(10 in acupuncture and 21 in acupuncture plus Chinese herbal medicine), and 12advanced-level doctorate degrees in AOM. The certification programs included one in East-Asian Medical Bodywork and 13 in CHM. Among these schools in 2023, institutions in the West and East Coast states comprised 67.86%(decreased from 77.42% in 2018) of the national total. California, Florida and Illinois represented 39.29%. There were 48 jurisdictions with acupuncture practice laws in place.The data suggests that the acupuncture profession in the U.S. has been significantly impacted during the coronavirus disease 2019 pandemic.

关键词： Acupuncture educational institution Acupuncturist Density Distribution Oriental medicine United States

Diagnose and treatment for Type D congenital esophageal atresia with tracheoesophageal fistula

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儿科学研究(英文) 2024年第1期8卷 37-43页

作者： Wang Dingding Zhao Yong Zhang Yanan Hua Kaiyun Gu Yichao Li Shuangshuang Liao Junmin Yang Shen Yang Ting Zhao Jiawei Huang Jinshi Department of Neonatal Surgery Beijing Children’s Hospital Capital Medical University National Center for Children’s Health Beijing China

Importance: Type D esophageal atresia (EA) with tracheoesophageal fistula (TEF) is characterized by EA with both proximal and distal TEFs. It is a rare congenital anomaly with a very low incidence.Objective: To investigate diagnostic and treatment strategies for this rare condition.Methods: We retrospectively reviewed the clinicopathological features of patients with EA/TEF treated at our institution between January 2007 and September 2021.Results: Among 386 patients with EA/TEF, 14 (3.6%) had type D EA/TEF. Only two patients were diagnosed with proximal TEF preoperatively. Seven patients were diagnosed intraoperatively. Five patients were missed for diagnosis during the initial surgery but was later confirmed by bronchoscopy. During the neonatal period, seven patients underwent a one-stage repair of proximal and distal TEF via thoracoscopy or thoracotomy. Due to missed diagnosis and other reasons, the other 7 patients underwent two-stage surgery for repair of the proximal TEF, including cervical incision and thoracoscopy. Ten of the 14 patients experienced postoperative complications including anastomotic leakage, pneumothorax, esophageal stricture, and recurrence. Patients who underwent one-stage repair of distal and proximal TEF during the neonatal period showed a higher incidence of anastomotic leak (4/7). In contrast, only one of seven patients with two-stage repair of the proximal TEF developed an anastomotic leak.Interpretation: Type D EA/TEF is a rare condition, and proximal TEFs are easily missed. Bronchoscopy may aim to diagnose and determine the correct surgical approach. A cervical approach may be more suitable for repairing the proximal TEF.

关键词： Diagnosis Therapy Tracheoesophageal fistula Type D congenital esophageal atresia