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Aryl hydrocarbon receptor:Linking environment to aging process in elderly patients with asthma

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Chinese Medical Journal 2024年第4期137卷 382-393页

作者： Tianrui Yang Rongjun Wan Wei Tu Sai Nithin Avvaru Peisong Gao division of allergy and Clinical Immunology Department of MedicineJohns Hopkins University School of MedicineBaltimoreMD 21224USA Department of Geriatric Medicine The First People’s Hospital of Yunnan ProvinceKunmingYunnan 650032China Department of Respiratory Medicine Xiangya HospitalCentral South UniversityChangshaHunan 410008China The State Key Laboratory of Respiratory disease for allergy Shenzhen Key Laboratory of Allergy and ImmunologyShenzhen University School of MedicineShenzhenGuangdong 518055China

Aging is a significant risk factor for various diseases,including asthma,and it often leads to poorer clinical outcomes,particularly in elderly individuals.It is recognized that age-related diseases are due to a time-dependent accumulation of cellular damage,resulting in a progressive decline in cellular and physiological functions and an increased susceptibility to chronic diseases.The effects of aging affect not only the elderly but also those of younger ages,posing significant challenges to global healthcare.Thus,understanding the molecular mechanisms associated with aging in different diseases is essential.One intriguing factor is the aryl hydrocarbon receptor(AhR),which serves as a cytoplasmic receptor and ligand-activated transcription factor and has been linked to the aging process.Here,we review the literature on several major hallmarks of aging,including mitochondrial dysfunction,cellular senescence,autophagy,mitophagy,epigenetic alterations,and microbiome disturbances.Moreover,we provide an overview of the impact of AhR on these hallmarks by mediating responses to environmental exposures,particularly in relation to the immune system.Furthermore,we explore how aging hallmarks affect clinical characteristics,inflammatory features,exacerbations,and the treatment of asthma.It is suggested that AhR signaling may potentially play a role in regulating asthma phenotypes in elderly populations as part of the aging process.

关键词： Aging Environment Reactive oxygen species Senescence Aryl hydrocarbon receptor Asthma

Longitudinal gut fungal alterations and potential fungal biomarkers for the progression of primary liver disease

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Science China(Life Sciences) 2024年第6期67卷 1183-1198页

作者： Shiman Jiang Lvwan Xu Yanfei Chen Zheyue Shu Longxian Lv Yuxi Zhao Kefan Bi Sisi Yang Qiangqiang Wang Lanjuan Li State Key Laboratory for Diagnosis and Treatment of infectious diseases National Clinical Research Center for Infectious DiseasesNational Medical Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China division of Hepatobiliary and Pancreatic Surgery Department of SurgeryThe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China

Liver disease,a major health concern worldwide,is a serious and progressive disorder.Herein,we not only established a mouse model of DEN+CCl4-induced primary liver disease but also collected clinical human samples to investigate longitudinal alterations in the gut mycobiome.As liver disease advanced,gut integrity was disrupted,and the mycobiota was disturbed in the mouse models.The metabolites associated with hepatocellular carcinoma(HCC)differed from those associated with the cirrhotic phase as follows:levels of stercobilin and aflatoxin B1 dialcohol were reduced,while levels of triterpenoids,bafilomycin A1,and DHEA were increased in the HCC group.The abundance of the phylum Chytridiomycota increased as the chronic liver disease progressed and was then replaced by the phylum Ascomycota in HCC.Based on the results from clinical human samples,the genus Candida(Ascomycota)(in humans)and the genus Kazachstania(Ascomycota)(in mice)occupied a dominant position in the HCC group,while other fungi were depleted.The increased abundance of C.albicans and depletion of S.cerevisiae may be hallmarks of the progression of liver cirrhosis to early HCC.Moreover,the administration of C.albicans and S.cerevisiae in the LC-HCC progression could accelerate or retard the progression of HCC.Therefore,gut fungi have the potential to serve as a noninvasive clinical biomarker and even a treatment method.

关键词： gut mycobiome liver disease longitudinal studies hepatocarcinogenesis fungal biomarker

Monocyte and macrophage function in respiratory viral infections

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Animal diseases 2024年第1期4卷 40-47页

作者： Mohd Arish Jie Sun Beirne B.Carter Center for Immunology Research University of VirginiaCharlottesvilleVA 22908USA division of infectious disease and International Health Department of MedicineUniversity of VirginiaCharlottesvilleVA 22908USA

Pulmonary macrophages,such as tissue-resident alveolar and interstitial macrophages and recruited monocyte-derived macrophages,are the major macrophages present in the lungs during homeostasis and diseased conditions.While tissue-resident macrophages act as sentinels of the alveolar space and play an important role in maintaining homeostasis and immune regulation,recruited macrophages accumulate in the respiratory tract after acute viral infections.Despite sharing similar anatomical niches,these macrophages are distinct in terms of their origins,surface marker expression,and transcriptional profiles,which impart macrophages with distinguished characteristics in physi-ological and pathophysiological conditions.In this review,we summarize the current view on these macrophage populations,their shared functions,and what makes them distinct from each other in the context of homeostasis andrespiratoryviral infections.

关键词： Alveolar macrophages Interstitial macrophages Monocytes derived macrophages Viral infection IAV RSV SARS-COV-2

Prevention of hepatitis B reactivation in patients with hematologic malignancies treated with novel systemic therapies:Who and Why?

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World Journal of Gastroenterology 2024年第5期30卷 509-511页

作者： Matteo Tonnini Clara Solera Horna Luca Ielasi Department of Medical and Surgical Sciences University of BolognaBologna 40138Italy division of Internal Medicine Hepatobiliary and Immunoallergic DiseasesIRCCS Azienda Ospedaliero-Universitaria di BolognaBologna 40138Italy infectious disease Unit Azienda USL-IRCCS di Reggio EmiliaReggio Emilia 42123Italy Department of Internal Medicine Ospedale degli Infermi di FaenzaFaenza 48018Italy

The risk of reactivation in patients with chronic or past/resolved hepatitis B virus(HBV)infection receiving chemotherapy or immunosuppressive drugs is a wellknown possibility.The indication of antiviral prophylaxis with nucleo(t)side analogue is given according to the risk of HBV reactivation of the prescribed therapy.Though the advent of new drugs is occurring in all the field of medicine,in the setting of hematologic malignancies the last few years have been characterized by several drug classes and innovative cellular treatment.As novel therapies,there are few data about the rate of HBV reactivation and the decision of starting or not an antiviral prophylaxis could be challenging.Moreover,patients are often treated with a combination of different drugs,so evaluating the actual role of these new therapies in increasing the risk of HBV reactivation is difficult.First results are now available,but further studies are still needed.Patients with chronic HBV infection[hepatitis B surface antigen(HBsAg)positive]are reasonably all treated.Past/resolved HBV patients(HBsAg negative)are the actual area of uncertainty where it could be difficult choosing between prophylaxis and pre-emptive strategy.

关键词： Hepatitis B reactivation Hepatitis B virus Antiviral prophylaxis Hematologic malignancies Chimeric antigens receptor-T cell therapy Immune checkpoint inhibitors

TREM-2 Drives Development of Multiple Sclerosis by Promoting Pathogenic Th17 Polarization

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Neuroscience Bulletin 2024年第1期40卷 17-34页

作者： Siying Qu Shengfeng Hu Huiting Xu Yongjian Wu Siqi Ming Xiaoxia Zhan Cheng Wang Xi Huang Center for Infection and Immunity and Guangdong Provincial Engineering Research Center of Molecular Imaging The Fifth Affiliated Hospital of Sun Yat-sen UniversityZhuhai 519000China The State Key Laboratory of Respiratory disease Guangdong Provincial Key Laboratory of Allergy and Clinical ImmunologyThe Second Affiliated HospitalGuangzhou Medical UniversityGuangzhou 510260China Department of Laboratory Medicine The First Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510080China division of Nephrology Department of Medicinethe Fifth Affliated Hospital of Sun Yat-sen UniversityZhuhai 519000China

Multiple sclerosis(MS)is a neuroinflammatory demyelinating disease,mediated by pathogenic T helper 17(Th17)cells.However,the therapeutic effect is accompa-nied by the fluctuation of the proportion and function of Th17 cells,which prompted us to find the key regulator of Th17 differentiation in MS.Here,we demonstrated that the triggering receptor expressed on myeloid cells 2(TREM-2),a modulator of pattern recognition receptors on innate immune cells,was highly expressed on pathogenic CD4-positive T lymphocyte(CD4^(+)T)cells in both patients with MS and experimental autoimmune encephalomyelitis(EAE)mouse models.Conditional knockout of Trem-2 in CD4^(+)T cells significantly alleviated the disease activity and reduced Th17 cell infiltration,activation,differentiation,and inflammatory cytokine production and secretion in EAE mice.Furthermore,with Trem-2 knockout in vivo experiments and in vitro inhibitor assays,the TREM-2/zeta-chain associated protein kinase 70(ZAP70)/signal transducer and activator of transcription 3(STAT3)signal axis was essential for Th17 activation and differentiation in EAE progression.In conclusion,TREM-2 is a key regulator of pathogenic Th17 in EAE mice,and this sheds new light on the potential of this therapeutic target for MS.

关键词： Multiple sclerosis Experimental autoimmune encephalomyelitis T helper 17 Triggering receptor expressed on myeloid cells 2

Harnessing SARS-CoV-2-specific CD8^(+)T cells to kill target tumor cells for cancer immunotherapy

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Cancer Communications 2024年第1期44卷 173-177页

作者： Keunok Jung Deok-Han Ko Jeong-Yun Jang Young Rong Kim Jung Yeon Heo Yong-Sung Kim Department of allergy and Clinical Immunology Ajou University School of MedicineSuwonRepublic of Korea Department of Molecular Science and Technology Ajou UniversitySuwonRepublic of Korea Department of infectious diseases Ajou University School of MedicineSuwonRepublic of Korea

Dear Editor,During the coronavirus disease 2019(COVID-19)pan-demic era,many individuals were naturally infected with or vaccinated against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),resulting in the p... 详细信息

关键词： acute respiratory immunotherapy

Treatment and prevention of epilepsy in onchocerciasis-endemic areas is urgently needed

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infectious diseases of Poverty 2024年第1期13卷 85-89页

作者： Robert Colebunders Joseph Nelson Siewe Fodjo Olivia Kamoen Luis-Jorge Amaral Amber Hadermann Chiara Trevisan Mark J.Taylor Julia Gauglitz Achim Hoerauf Yasuaki Sato Katja Polman Maria-Gloria Basanez Dan Bhwana Thomson Lakwo Gasim Abd-Elfarag Sebastien D.Pion Global Health Institute University of AntwerpAntwerpBelgium Department of Neurology Heilig Hart ZiekenhuisLierBelgium Department of Public Health Institute of Tropical MedicineAntwerpBelgium Liverpool School of Tropical Medicine LiverpoolUK Department of Computer Science University of AntwerpAntwerpBelgium Institute of Medical Microbiology Immunology and ParasitologyUniversity Hospital BonnBonnGermany German Center for Infection Research(DZIF) Partner Site Bonn-CologneBonnGermany School of Global Humanities and Social Sciences Nagasaki UniversityNagasakiJapan MRC Centre for Global infectious disease Analysis and London Centre for Neglected Tropicaldisease Research Department of Infectious Disease EpidemiologySchool of Public HealthImperial College LondonLondonUK National Institute for Medical Research TangaTanzania Vector Control division Ministry of HealthKampalaUganda School of Public Health University of JubaJubaSouth Sudan Access for Humanity JubaSouth Sudan French National Research Institute for Sustainable Development MontpellierFrance

Background There is increasing epidemiological evidence supporting the association between onchocerciasis and seizures,reinforcing the concept of onchocerciasis-associated epilepsy(OAE).The aim of this paper is to provide an update on the new knowledge about OAE and to propose recommendations to the World Health Organization how to address this public health problem.Main text During the 2nd International Workshop on OAE held on 19-21 September,2023,in Antwerp,Belgium,participants recognised OAE as a substantial yet neglected public health problem,particularly in areas of sub-Saharan Africa where onchocerciasis remains hyperendemic.Evidence from prospective population-based studies suggest that strengthening onchocerciasis elimination efforts leads to a significant reduction of OAE incidence.There is a need to validate an OAE case definition to estimate the burden of disease and identify onchocerciasis-endemic areas requiring intensification of onchocerciasis elimination programmes and integration of epilepsy care t is expected that raising awareness about OAE will boost the population uptake of ivermectin.The implementation of a commu-nity-based epilepsy treatment programme offering free anti-seizure medications(ASMs)has shown high effectiveness in reducing the frequency of seizures and improving the overall quality of life of people with epilepsy.Conclusions To reduce OAE burden,enhanced collaboration between onchocerciasis and mental health pro-grammes at community,national,and international levels is required.Urgent efforts are needed to ensure the uninter-rupted provision of free ASMs in onchocerciasis-endemic areas.Furthermore,OAE should be included in the quantif-cation of the onchocerciasis disease burden.

关键词： Onchocerciasis Morbidity Burden of disease Prevention Ivermectin Epilepsy Nodding syndrome Treatment Children Policy

Impact of ursodeoxycholic acid therapy in autoimmune liver disease patients with COVID-19 and its clinical prognosis

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生物安全与健康(英文) 2024年第3期6卷 165-170页

作者： Li Minghui Cao Weihua Jiang Tingting Deng Wen Wang Shiyu Wu Shuling Zhang Lu Lu Yao Chang Min Liu Ruyu Ding Xiaoyan Shen Ge Gao Yuanjiao Hao Hongxiao Chen Xiaoxue Hu Leiping Xu Mengjiao Jiang Yuyong Yi Wei Xie Yao Song Rui Department of Hepatology division Beijing Ditan Hospital Capital Medical University Beijing China Department of Hepatology division Peking University Ditan Teaching Hospital Beijing China Department of Medical Oncology Beijing Ditan Hospital Capital Medical University Beijing China Center of Integrative Medicine Beijing Ditan Hospital Capital Medical University Beijing China Department of Gynecology and Obstetrics Beijing Ditan Hospital Capital Medical University Beijing China Department of infectious disease Beijing Ditan Hospital Capital Medical University Beijing China

To explore the impact of ursodeoxycholic acid (UDCA) on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and clinical outcomes in patients with autoimmune liver disease (AILD). Patients diagnosed with AILD were enrolled and divided into a UDCA group and a non-UDCA group based on whether they received UDCA treatment. Relevant data were collected regarding AILD diagnosis, treatment, biochemical indicators, and imaging examination. The incidence of SARS-CoV-2 infection and the prognosis of AILD patients were observed. A total of 1,138 patients completed follow-up. The usage rate of hormone (P = 0.003) and immunosuppressant (P = 0.001) used for treating AILD in the non-UDCA group was markedly lower than in the UDCA group. The UDCA usage rate was markedly lower in SARS-CoV-2 infected patients than in uninfected patients (P = 0.003). The rate of SARS-CoV-2 infection in the non-UDCA group was significantly higher than in the UDCA group (P = 0.018). Logistic regression analysis showed that UDCA use (P = 0.003) was correlated to a lower incidence of SARS-CoV-2, while immunosuppressant use (P = 0.017) increased the incidence. Recovery time from SARS-CoV-2 infection was markedly longer for those receiving UDCA treatment than those in the non-UDCA group (P = 0.018). UDCA is associated with low SARS-CoV-2 incidence in AILD patients, while immunosuppressant increases its incidence instead. Patients receiving UDCA treatment have a longer recovery time after being infected.

关键词： Ursodeoxycholic acid (UDCA) Autoimmune liver disease (AILD) Coronavirus disease 2019 (COVID-19) Primary biliary cholangitis (PBC) Autoimmune hepatitis (AIH)

Design,synthesis,and biological evaluation of 1,2,4-triazole derivatives as potent antitubercular agents

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Chinese Chemical Letters 2024年第3期35卷 326-331页

作者： Yu Wen Shichun Lun Yuxue Jiao Wei Zhang Tianyu Hu Ting Liu Fan Yang Jie Tang Bing Zhang William R.Bishai Li-Fang Yu Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development School of Chemistry and Molecular EngineeringEast China Normal UniversityShanghai 200062China Center for Tuberculosis Research Department of MedicineDivision of Infectious DiseaseJohns Hopkins School of MedicineBaltimoreMD21231-1044United States Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology ShanghaiTech UniversityShanghai 201210China Shanghai Key Laboratory of Green Chemistry and Chemical Process School of Chemistry and Molecular EngineeringEast China Normal UniversityShanghai 200062China

Inhibition of mycobacterial membrane protein large 3(MmpL3)thereby affecting the mycolic acid biosynthetic pathway has been proven to be an effective strategy for developing antitubercular drugs.Based on the X-ray crystal structure of MmpL3 inhibitor complexes,a series of novel 1,2,4-triazole derivatives were designed,synthesized and evaluated antitubercular activity against Mtb strain H37Rv.Comprehensive structure–activity relationship exploration resulted in the identification of compounds 21 and 28,which possess potent antitubercular activity against Mtb strain H37Rv[minimum inhibitory concentration(MIC)=0.03–0.13μg/mL]and the clinical isolates of multidrug resistance(MDR)and extensive drug resistance(XDR)tuberculosis(MIC=0.06–1.0μg/mL).Moreover,compounds 21 and 28 showed neglectable cytotoxicity(IC_(50)≥32μg/mL)to the mammalian Vero cells and favorable physicochemical and pharmacokinetic properties according to the in silico absorption,distribution,metabolism and excretion(ADME)prediction.Finally,the potential target of representative 1,2,4-triazole 28 was identified to be MmpL3 using a microscale thermophoresis(MST)assay.

关键词： Tuberculosis MDR and XDR-TB MmpL3 inhibitor 1 2 4-Triazole Structure-based drug design