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Molybdenum and cadmium co-induce necroptosis through th1/th2 imbalance-mediated endoplasmic reticulum stress in duck ovaries

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Journal of Environmental Sciences 2024年第8期142卷 92-102页

作者： Ting Cui Xueyan Dai Huiling Guo Dianyun Wang Bingyan Huang Wenjing Pu Xuesheng Chu Caiying Zhang Jiangxi Provincial Key Laboratory for Animal Health Institute of Animal Population HealthCollege of Animal Science and TechnologyJiangxi Agricultural UniversityNanchang 330045China

Cadmium(Cd)and excess molybdenum(Mo)pose serious threats to animal health.Our previous study has determined that Cd and/or Mo exposure can cause ovarian damage of ducks,while the specific mechanism is still obscure.To further investigate the toxic mechanism of Cd and Mo co-exposure in the ovary,forty 8-day-old female ducks were randomly allocated into four groups for 16 weeks,and the doses of Cd and Mo in basic diet per kg were as follows:control group,Mo group(100 mg Mo),Cd group(4 mg Cd),and Mo+Cd group(100 mg Mo+4 mg Cd).Cadmium sulfate 8/3-hydrate(CdSO_(4)·8/3H_(2)O)and hexaammonium molybdate((NH_(4))_(6)Mo_(7)O_(24)·4H_(2)O)were the origins of Cd and Mo,respectively.At the 16th week of the experiment,all ovary tissues were collected for the detection of related indexes.the data indicated that Mo and/or Cd induced trace element disorders and th1/th2 balance to divert toward th1 in the ovary,which activated endoplasmic reticulum(ER)stress and then provoked necroptosis through triggering RIPK1/RIPK3/MLKL signaling pathway,and eventually caused ovarian pathological injuries and necroptosis characteristics.the alterations of above indicators were most apparent in the joint group.Above all,this research illustrates that Mo and/or Cd exposure can initiate necroptosis through th1/th2 imbalance-modulated ER stress in duck ovaries,and Mo and Cd combined exposure aggravates ovarian injuries.this research explores the molecular mechanism of necroptosis caused by Mo and/or Cd,which reveals that ER stress attenuation may be a therapeutic target to alleviate necroptosis.

关键词： Molybdenum Cadmium th1/th2 imbalance Endoplasmic reticulum stress Necroptosis Ovary

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Exposure to ephedrine attenuates th1/th2 imbalance underlying OVA-induced asthma through airway epithelial cell-derived exo-somal lnc-TRPM2-AS

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Chinese Journal of Natural Medicines 2024年第6期22卷 530-540页

作者： HU Yan WANG Mengqing XIE Jing JIAO Luojia DING Yi LUO Yinhe Department of Pediatrics The First Hospital of Hunan University of Chinese MedicineChangsha 410007China Hunan University of Chinese Medicine Changsha 410208China Department of Rehabilitation Medical CollegeChangsha Civil Affairs Vocational and Technical CollegeChangsha 410004Hunan ProvinceChina Teaching and Research Office of Chinese and Western Combination Hunan University of Chinese MedicineChangsha 410208China

Although various anti-inflammatory medications,such as ephedrine,are employed to manage cough-variant asthma,their underlying mechanisms are yet to be fully understood.Recent studies suggest that exosomes derived from airway epithelial cells(AECs)contain components like messenger RNAs(mRNAs),micro-RNAs(miRNAs),and long noncoding RNA(lncRNA),which play roles in the occurrence and progression of airway inflammation.this study investigates the influence of AEC-derived exosomes on the efficacy of ephedrine in treating cough-variant asthma.We established a mouse model of asthma and measured airway resist-ance and serum inflammatory cell levels.Real-time polymerase chain reaction(RT-qPCR),Western blotting,and enzyme-linked im-munosorbent assay(ELISA)analyses were used to assess gene and protein expression levels.Exosomes were isolated and character-ized.RNA immunoprecipitation(RIP)and RNA pull-down assays were conducted to examine the interaction between hnRNPA2B1 and lnc-TRPM2-AS1.In the ovalbumin(OVA)-challenged mouse model,ephedrine treatment reduced inflammatory responses,air-way resistance,and th1/th2 cell imbalance.Exosomes from OVA-treated AECs showed elevated levels of lnc-TRPM2-AS1,which were diminished following ephedrine treatment.the exosomal lnc-TRPM2-AS1 mediated the th1/th2 imbalance in CD4^(+)T cells,with its packaging into exosomes being facilitated by hnRNPA2B1.this study unveils a novel mechanism by which ephedrine ameli-orates OVA-induced CD4^(+)T cell imbalance by suppressing AEC-derived exosomal lnc-TRPM2-AS1.these findings could provide a theoretical framework for using ephedrine in asthma treatment.

关键词： Asthma Ephedrine Exosomal lnc-TRPM2-AS1 th1/th2 imbalance HnRNPA2B1 Airway epithelial cells

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HSPT Modulates the Immunity via Attenuating th1/th2 imbalance in an Immunosuppressed Mouse Model

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Journal of Traditional Chinese Medicine 2021年

作者： XuefeiLuo TaijinLan MingyueMo ZhenxingChen FeiLuo SiyinHan PengLiu ZhongxiuLiang TingZhang TianyiLi QiangqiangYan YongLin JiangLin RuikangHospitalAffiliatedtoGuangxiUniversityofChineseMedicine SchoolofBasicMedicalScience，GuangxiUniversityofChineseMedicine BeihaiBaozhulinMarineTechnologyCo.Ltd.

Abstract OBJECTIVE: To investigate whether Hydrolyzed Seawater Pearl Tablet （HSPT） could modulate the th1/th2 imbalance in an immunosuppressed mouse model with th1 to th2 shift induced by Cyclosporine A （CsA） which can be used in the clinical treatment of th2 to th1 shift diseases， and explore the possible mechanism for the adjuvant therapeutic efficacy of HSPT on RRI and AIDS. MEthODS: the mice were randomly divided into six groups of five animals each， namely normal group， model group， Lentinan polysaccharide tablet （LPT） group， and three HPST treated groups. HPST treated groups were administered with HPST （0.51 g/kg， 1.02 g/kg， 2.04 g/kg） via intragastric gavage （i.g） for 30 consecutive days. LPT used as reference drug for positive control， LPT group was administered with LPT （8.2 mg/kg） for 30 consecutive days. Normal group and model group were received only distilled water. the animals of model group， LPT group and HPST treated groups were intraperitoneal injection （i.p） with CsA （50 mg/kg） to establish the immunosuppressed mice model with th1 to th2 shift on the 20th， 22th and 24th day， one hour after the administration of the respective treatment. Animals were sacrificed one hour after the last administration to collect the blood， splenic tissue and hepatic tissue samples. the proportion of T cells including CD8;and CD4;T cells， th1 and th2 in peripheral blood of experimental mice were measured by flow cytometric. the protein expression in serum and mRNA expression in splenic tissue of experimental mice for IL-2， IL-12， IFN-γ， IL-4， IL-6， IL-10 and IL-13 were measured by enzyme linked immunosorbent assay （ELISA） and fluorescence quantitative polymerase chain reaction （PCR） respectively. RESULTS: HSPT elevated the proportion of T cells including both CD8;and CD4;T cells， in which the proportion of th1 and th2 cells increased， while the ratio of th1/th2 cells decreased in peripheral blood of an immunosuppressed mouse model with th1 to th2 shift induced by CsA. Furthermore， HSPT enhanced th1-type cytokines IL

关键词： Hydrolyzed Seawater Pearl Tablet(HSPT) Immunosuppressed th1/th2 imbalance

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Down-regulation of Notch Signaling Pathway Reverses the th1/th2 imbalance in Tuberculosis Patients

Down-regulation of Notch Signaling Pathway Reverses the Th1/...

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第十二届全国免疫学学术大会

作者： LI QIFENG ZHANG HUI YU LIANG WU CHAO LUO XINHUI SUN HE DING JIANBING People's Hospital of Xinjiang Uygur Autonomous Region School of Preclinical Medicine Xinjiang Medical University

Objective:th1/th2 imbalance to th2 is of significance in the peripheral immune responses in Tuberculosis(TB) development.However,the mechanisms for th1/th2 imbalance are still not well determined.Notch signaling pathway is involved in the peripheral T cell activation and effector cell differentiation.However,whether it affects th1/th2 imbalance in TB patients is still not known.Methods We used y-secretase inhibitor(DAPT) to treat the peripheral blood mononuclear cells(PBMCs) from healthy people or individuals with latent or active TB infection in vitro,respectively.then,the th1/th2 ratios were determined by flow cytometry,and cytokines of IFN-γ,IL-4,IL-10 in the culture supernatant were measured by CBA method.the Notch signal pathway associated proteins Hes1,GATA3 and T-bet were quantitated by real-time PCR or immunoblotting.Results It showed that DAPT effectively inhibited the protein level of Hes1.In TB patients,the th2 ratio increased in the PBMCs,alone with the high expression of GATA3 and IL-4,resulting in the high ratios of th2/th1 and GATA3/T-bet in TB patients.However,th2 cells ratio decreased after blocking the Notch signaling pathway by DAPT and the th2/th1 ratio in TB patients were DAPT dose-dependent,accompanied by the decrease of IL-4 and GATA3.But,its influence on th1 ratio and th1 related T-bet and IFN-γ levels were not significant.Conclusion Our results suggest that blocking Notch signaling by DAPT could inhibit th2 responses and restore th1/th2 imbalance in TB patients.

关键词： Notch signaling pathway th1/th2 imbalance Tuberculosis

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