期刊：
Brain and Behavior,2024年14(2):e3373- ISSN：2162-3279
通讯作者：
Chen, YJ
作者机构：
[Chen, Liang; Chen, Yongjun; Xie, Yangzhi] Univ South China, Affiliated Nanhua Hosp, Hengyang Med Sch, Dept Neurol, Hengyang 421001, Peoples R China.;[Chen, Jiacheng] Univ South China, Affiliated Nanhua Hosp, Hengyang Med Sch, Dept Intens Care Unit, Hengyang, Peoples R China.
通讯机构：
[Chen, YJ ] U;Univ South China, Affiliated Nanhua Hosp, Hengyang Med Sch, Dept Neurol, Hengyang 421001, Peoples R China.
关键词：
M1/M2 polarization;neuroinflammation;Parkinson's disease;regulatory T cell;vitamin D receptor
摘要：
We explored the therapeutic effects of vitamin receptor activation by calcitriol in a mouse model of PD. We found that calcitriol is potent to protect against neuroinflammation and neuronal degeneration by boosting Treg. Vitamin D receptor may be a therapeutic option for PD. Abstract Objective Vitamin D deficiency is a risk factor for Parkinson's disease (PD) and vitamin D supplementation robustly alleviates neurodegeneration in PD models. However, the mechanisms underlying this effect require further clarification. Current evidence suggests that harnessing regulatory T cells (Treg) may mitigate neuronal degeneration. In this study, we investigated the therapeutic effects of vitamin D receptor activation by calcitriol on PD, specifically focusing on its role in Treg. Methods Hemiparkinsonian mice model was established through the injection of 6‐OHDA into the striatum. Mice were pretreated with calcitriol before 6‐OHDA injection. The motor performance, dopaminergic neuronal survival, contents of dopamine, and dopamine metabolites were evaluated. The pro‐inflammatory cytokines levels, T‐cell infiltration, mRNA expression of indicated microglial M1/M2 phenotypic markers, and microglial marker in the midbrain were detected. Populations of Treg in the splenic tissues were assessed using a flow cytometry assay. PC61 monoclonal antibody was applied to deplete Treg in vivo. Results We show that calcitriol supplementation notably improved motor performance and reduced dopaminergic degeneration in the 6‐OHDA‐induced PD model. Mechanistically, calcitriol promoted anti‐inflammatory/neuroprotective Treg and inhibited pro‐inflammatory/neurodestructive effector T‐cell generation in this model. This process significantly inhibited T‐cell infiltration in the midbrain, restrained microglial activation, microglial M1 polarization, and decreased pro‐inflammatory cytokines release. This more favorable inflammatory microenvironment rescued dopaminergic degeneration. To further verify that the anti‐inflammatory effects of calcitriol are associated with Treg expansion, we applied an antibody‐mediated Treg depletion assay. As predicted, the anti‐inflammatory effects of calcitriol in the PD model were diminished following Treg depletion. Conclusion These findings suggest that calcitriol's anti‐inflammatory and neuroprotective effects in PD are associated with its potential to boost Treg expansion.
期刊：
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION,2024年331(10):840-849 ISSN：0098-7484
通讯作者：
Li, Fengli;Zi, WJ
作者机构：
[Xu, Xu; Peng, Zhouzhou; Yu, Nizhen; Jiang, Lin; Ma, Jinfu; Huang, Jiacheng; Zi, Wenjie; Li, Linyu; Tian, Yan; Fan, Shitao; Xie, Dongjing; Guo, Changwei; Liu, Xiang; Song, Jiaxing; Yue, Chengsong; Huang, Jiandi; Zi, WJ; Yang, Qingwu; Qiu, Zhongming; Li, Fengli; Hu, Jinrong; Yang, Jie; Yang, Dahong] Third Mil Med Univ, Mil Med Univ 3, Xinqiao Hosp, Dept Neurol, 183 Xinqiao Main St, Chongqing 400037, Peoples R China.;[Xu, Xu; Peng, Zhouzhou; Yu, Nizhen; Jiang, Lin; Ma, Jinfu; Huang, Jiacheng; Zi, Wenjie; Li, Linyu; Tian, Yan; Fan, Shitao; Xie, Dongjing; Guo, Changwei; Liu, Xiang; Song, Jiaxing; Yue, Chengsong; Huang, Jiandi; Zi, WJ; Yang, Qingwu; Qiu, Zhongming; Li, Fengli; Hu, Jinrong; Yang, Jie; Yang, Dahong] Third Mil Med Univ, Army Med Univ, Affiliated Hosp 2, 183 Xinqiao Main St, Chongqing 400037, Peoples R China.;[Chen, Yifei] Kunming Med Univ, Dept Neurol, Affiliated Hosp 1, Kunming, Peoples R China.;[Zheng, Chong] Fujian Med Univ, Dept Neurol, Longyan Affiliated Hosp 1, Longyan, Peoples R China.;[Jiang, Shunfu] Jingdezhen 1 Peoples Hosp, Dept Neurol, Jingdezhen, Peoples R China.
通讯机构：
[Zi, WJ ; Li, FL] T;Third Mil Med Univ, Mil Med Univ 3, Xinqiao Hosp, Dept Neurol, 183 Xinqiao Main St, Chongqing 400037, Peoples R China.;Third Mil Med Univ, Army Med Univ, Affiliated Hosp 2, 183 Xinqiao Main St, Chongqing 400037, Peoples R China.
摘要：
IMPORTANCE: It is uncertain whether intravenous methylprednisolone improves outcomes for patients with acute ischemic stroke due to large-vessel occlusion (LVO) undergoing endovascular thrombectomy. OBJECTIVE: To assess the efficacy and adverse events of adjunctive intravenous low-dose methylprednisolone to endovascular thrombectomy for acute ischemic stroke secondary to LVO. DESIGN, SETTING, AND PARTICIPANTS: This investigator-initiated, randomized, double-blind, placebo-controlled trial was implemented at 82 hospitals in China, enrolling 1680 patients with stroke and proximal intracranial LVO presenting within 24 hours of time last known to be well. Recruitment took place between February 9, 2022, and June 30, 2023, with a final follow-up on September 30, 2023. INTERVENTIONS: Eligible patients were randomly assigned to intravenous methylprednisolone (n = 839) at 2 mg/kg/d or placebo (n = 841) for 3 days adjunctive to endovascular thrombectomy. MAIN OUTCOMES AND MEASURES: The primary efficacy outcome was disability level at 90 days as measured by the overall distribution of the modified Rankin Scale scores (range, 0 [no symptoms] to 6 [death]). The primary safety outcomes included mortality at 90 days and the incidence of symptomatic intracranial hemorrhage within 48 hours. RESULTS: Among 1680 patients randomized (median age, 69 years; 727 female [43.3%]), 1673 (99.6%) completed the trial. The median 90-day modified Rankin Scale score was 3 (IQR, 1-5) in the methylprednisolone group vs 3 (IQR, 1-6) in the placebo group (adjusted generalized odds ratio for a lower level of disability, 1.10 [95% CI, 0.96-1.25]; P = .17). In the methylprednisolone group, there was a lower mortality rate (23.2% vs 28.5%; adjusted risk ratio, 0.84 [95% CI, 0.71-0.98]; P = .03) and a lower rate of symptomatic intracranial hemorrhage (8.6% vs 11.7%; adjusted risk ratio, 0.74 [95% CI, 0.55-0.99]; P = .04) compared with placebo. CONCLUSIONS AND RELEVANCE: Among patients with acute ischemic stroke due to LVO undergoing endovascular thrombectomy, adjunctive methylprednisolone added to endovascular thrombectomy did not significantly improve the degree of overall disability. TRIAL REGISTRATION: ChiCTR.org.cn Identifier: ChiCTR2100051729.
作者机构：
[Wei, Rui; Liu, Qingqing; Luo, Jun-Li; Wei, R; Sun, Yangqing; Luo, JL] Cent South Univ, Xiangya Hosp, Dept Oncol, Changsha 410008, Peoples R China.;[Zhong, Shangwei; Luo, Jun-Li; Luo, JL] Univ South China, Affiliated Hosp 2, Canc Res Inst, Hengyang Med Sch, Hengyang 421001, Peoples R China.;[Luo, Jun-Li; Luo, JL] Hunan Prov Maternal & Child Hlth Care Hosp, Natl Hlth Commiss, Key Lab Birth Defect Res & Prevent, Changsha 410008, Peoples R China.
通讯机构：
[Wei, R; Luo, JL ] C;Cent South Univ, Xiangya Hosp, Dept Oncol, Changsha 410008, Peoples R China.;Univ South China, Affiliated Hosp 2, Canc Res Inst, Hengyang Med Sch, Hengyang 421001, Peoples R China.;Hunan Prov Maternal & Child Hlth Care Hosp, Natl Hlth Commiss, Key Lab Birth Defect Res & Prevent, Changsha 410008, Peoples R China.
关键词：
FTSJ1;tumor promotor;CD8+T cell infiltration;triple-negative breast cancer
摘要：
Simple Summary In this study, we found that high FTSJ1 expression in triple-negative breast cancer patients was associated with poor prognosis and was associated with reduced infiltration of CD8+T cells in the tumor microenvironment. By knocking down FTSJ1, we observed an inhibitory effect on the proliferation and migration of triple-negative breast cancer, while inducing apoptosis and increasing the sensitivity of TNBC cells to T-cell-mediated cytotoxicity. This finding highlights the importance of FTSJ1 as a potential immunotherapy target in triple-negative breast cancer.Abstract FtsJ RNA 2 '-O-methyltransferase 1 (FTSJ1) is a member of the methyltransferase superfamily and is involved in the processing and modification of ribosomal RNA. We herein demonstrate that FTSJ1 favors TNBC progression. The knockdown of FTSJ1 inhibits TNBC cell proliferation and development, induces apoptosis of cancer cells, and increases the sensitivity of TNBC cells to T-cell-mediated cytotoxicity. Furthermore, the high expression of FTSJ1 in TNBC attenuates CD8+T cell infiltration in the tumor microenvironment (TME) correlated with poorer prognosis for clinical TNBC patients. In this study, we establish that FTSJ1 acts as a tumor promotor, is involved in cancer immune evasion, and may serve as a potential immunotherapy target in TNBC.
摘要：
AKG protects against CTX‐induced POI by inhibiting NLRP3‐mediated pyroptosis of granulosa cells, restoring the glycolysis and improving ovarian reserve function.(Created with BioRender.com). Scope Premature ovarian insufficiency (POI) is a common female infertility problem, with its pathogenesis remains unknown. The NOD‐like receptor family pyrin domain‐containing 3 (NLRP3)‐mediated pyroptosis has been proposed as a possible mechanism in POI. This study investigates the therapeutic effect of α‐ketoglutarate (AKG) on ovarian reserve function in POI rats and further explores the potential molecular mechanisms. Methods and results POI rats are caused by administration of cyclophosphamide (CTX) to determine whether AKG has a protective effect. AKG treatment increases the ovarian index, maintains both serum hormone levels and follicle number, and improves the ovarian reserve function in POI rats, as evidence by increased the level of lactate and the expression of rate‐limiting enzymes of glycolysis in the ovaries, additionally reduced the expression of NLRP3, Gasdermin D (GSDMD), Caspase‐1, Interleukin‐18 (IL‐18), and Interleukin‐1 beta (IL‐1β). In vitro, KGN cells are treated with LPS and nigericin to mimic pyroptosis, then treated with AKG and MCC950. AKG inhibits inflammatory and pyroptosis factors such as NLRP3, restores the glycolysis process in vitro, meanwhile inhibition of NLRP3 has the same effect. Conclusion AKG ameliorates CTX‐induced POI by inhibiting NLRP3‐mediated pyroptosis, which provides a new therapeutic strategy and drug target for clinical POI patients.
作者机构：
[Feng, Wen-Jie; Wu, Xiao-Ping; Zhu, Hong -Bo; He, Zhi-Long; Tan, Ye-Ru; Xun, Yi; Li, Yue-Hua; Jiang, Yi-Ling; Zhu, HB] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Med Oncol, Hengyang, Hunan, Peoples R China.;[Jiang, Bao-Hong] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Pharm, Hengyang, Hunan, Peoples R China.
通讯机构：
[Zhu, HB ] U;Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Med Oncol, Hengyang, Hunan, Peoples R China.
关键词：
AIFM2;GPX4;circRNAs;hepatocellular cancer (HCC);miR-6085
摘要：
BACKGROUND: Circular RNAs (circRNAs) represent a subset of non-coding RNAs implicated in the regulation of diverse biological processes, including tumorigenesis. However, the expression and functional implications of circ0060467 in hepatocellular carcinoma (HCC) remain elusive. In this study, we aimed to elucidate the role of circ0060467 in modulating the progression of HCC. METHODS: Differentially expressed circRNAs in HCC tissues were identified through circRNA microarray assays. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) assays revealed the upregulation of circ0060467 in both HCC cell lines and tissues. Various assays were conducted to investigate the roles of circ0060467 in HCC progression. Additionally, RNA immunoprecipitation (RIP) assays and luciferase assays were carried out to assess the interactions between circ0060467, microRNA-6085 (miR-6085), apoptosis-inducing factor mitochondria-associated 2 (AIFM2), and glutathione peroxidase 4 (GPX4) in HCC. RESULTS: Microarray and qRT-PCR analyses demonstrated a marked elevation of circ0060467 in HCC tissues and cell lines. Knockdown of circ0060467 suppressed HCC cell proliferation. Luciferase reporter and RIP assays confirmed the binding of circ0060467, AIFM2, and GPX4 to miR-6805. Subsequent experiments revealed that circ0060467 competes with AIFM2 and GPX4, thereby inhibiting cancer cell ferroptosis by binding to miR-6085 and promoting hepatocellular carcinoma progression. CONCLUSIONS: Collectively, circ0060467 modulates the levels of AIFM2 and GPX4, crucial regulators of tumor cell ferroptosis, by acting as a sponge for miR-6085 in HCC. Thus, circ0060467 may represent a novel diagnostic marker and therapeutic target for HCC.
摘要：
The permeability of the blood-brain barrier (BBB) is increased in Alzheimer's disease (AD). This plays a key role in the instigation and maintenance of chronic inflammation during AD. Experiments using AD models showed that the increased permeability of the BBB was mainly caused by the decreased expression of tight junction-related proteins occludin and claudin-5. In this study, we found that ZNF787 and HDAC1 were upregulated in β-amyloid (Aβ)(1-42)-incubated endothelial cells, resulting in increased BBB permeability. Conversely, the silencing of ZNF787 and HDAC1 by RNAi led to reduced BBB permeability. The silencing of ZNF787 and HDAC1 enhanced the expression of occludin and claudin-5. Mechanistically, ZNF787 binds to promoter regions for occludin and claudin-5 and functions as a transcriptional regulator. Furthermore, we demonstrate that ZNF787 interacts with HDAC1, and this resulted in the downregulation of the expression of genes encoding tight junction-related proteins to increase in BBB permeability. Taken together, our study identifies critical roles for the interaction between ZNF787 and HDAC1 in regulating BBB permeability and the pathogenesis of AD.
期刊：
FRONTIERS IN IMMUNOLOGY,2024年15:1289644 ISSN：1664-3224
通讯作者：
Li, ZY
作者机构：
[Li, Zhongyu; Fang, Chunxia; Li, ZY; Wang, Xinglv; Wu, Hongrong] Univ South China, Inst Pathogen Biol, Hengyang Med Coll, Sch Nursing,Hunan Prov Key Lab Special Pathogens P, Hengyang, Peoples R China.
通讯机构：
[Li, ZY ] U;Univ South China, Inst Pathogen Biol, Hengyang Med Coll, Sch Nursing,Hunan Prov Key Lab Special Pathogens P, Hengyang, Peoples R China.
关键词：
Chlamydia trachomatis;immune evasion;innate immune cells;innate immunity;survival and growth
摘要：
Chlamydia trachomatis, is a kind of obligate intracellular pathogen. The removal of C. trachomatis relies primarily on specific cellular immunity. It is currently considered that CD4(+) Th1 cytokine responses are the major protective immunity against C. trachomatis infection and reinfection rather than CD8(+) T cells. The non-specific immunity (innate immunity) also plays an important role in the infection process. To survive inside the cells, the first process that C. trachomatis faces is the innate immune response. As the "sentry" of the body, mast cells attempt to engulf and remove C. trachomatis. Dendritic cells present antigen of C. trachomatis to the "commanders" (T cells) through MHC-I and MHC-II. IFN-γ produced by activated T cells and natural killer cells (NK) further activates macrophages. They form the body's "combat troops" and produce immunity against C. trachomatis in the tissues and blood. In addition, the role of eosinophils, basophils, innate lymphoid cells (ILCs), natural killer T (NKT) cells, γδT cells and B-1 cells should not be underestimated in the infection of C. trachomatis. The protective role of innate immunity is insufficient, and sexually transmitted diseases (STDs) caused by C. trachomatis infections tend to be insidious and recalcitrant. As a consequence, C. trachomatis has developed a unique evasion mechanism that triggers inflammatory immunopathology and acts as a bridge to protective to pathological adaptive immunity. This review focuses on the recent advances in how C. trachomatis evades various innate immune cells, which contributes to vaccine development and our understanding of the pathophysiologic consequences of C. trachomatis infection.
作者机构：
[Tang, Dan; Xiang, Xing; Yi, Linfeng] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Inst Microbiol & Infect Dis,Dept Clin Lab Med, Hengyang, Hunan, Peoples R China.;[Tang, Huifang; Huang, Hong; Tang, Dan; Xiang, Xing; Yi, Linfeng; Tang, HF] Clin Res Ctr Myocardial Injury Hunan Prov, Hengyang, Hunan, Peoples R China.;[Tang, Huifang; Huang, Hong; Tang, Dan; Xiang, Xing; Yi, Linfeng; Tang, HF] Univ South China, Affiliated Hosp 1, Inst Cardiovasc Dis, Hengyang Med Sch, Hengyang, Hunan, Peoples R China.;[Tang, Huifang; Huang, Hong; Tang, Dan; Xiang, Xing; Yi, Linfeng; Tang, HF] Univ South China, Hunan Prov Key Lab Multiom & Artificial Intelligen, Hengyang, Hunan, Peoples R China.;[Xiao, Chungang] Hunan Univ Med Gen Hosp, Dept Orthoped, Huaihua, Hunan, Peoples R China.
通讯机构：
[Huang, H ; Tang, HF] C;Clin Res Ctr Myocardial Injury Hunan Prov, Hengyang, Hunan, Peoples R China.;Univ South China, Affiliated Hosp 1, Inst Cardiovasc Dis, Hengyang Med Sch, Hengyang, Hunan, Peoples R China.;Univ South China, Hunan Prov Key Lab Multiom & Artificial Intelligen, Hengyang, Hunan, Peoples R China.;Univ South China, Hunan Prov Key Lab Multiom & Artificial Intelligen, Hengyang 421001, Hunan, Peoples R China.
关键词：
Titin;heart failure;lactylation;sarcomeric structure and function;α-MHC
摘要：
Lactylation of alpha-myosin heavy chain (alpha-MHC) has recently been reported to preserve sarcomeric structure and function and attenuate the development of heart failure. Specifically, lactylation enhanced the interaction of alpha-MHC with the sarcomeric protein Titin, thereby maintaining normal sarcomeric structure and myocardial contractile function. Furthermore, the administration of lactate or inhibition of lactate efflux potentially treats heart failure by restoring lactylation of alpha-MHC and the interaction of alpha-MHC with Titin. This finding highlights the significant role of alpha-MHC lactylation in myocardial diseases and presents a new therapeutic target for the treatment of heart failure.
摘要：
This paper expounds the intrusion detection based on clustering and the boundary point detection of the specific models, and the clustering analysis technology has carried on the detailed description, and then analyzed the result of the experiment environment and experiment, further validation of this project is based on the improved NPRIM algorithm applied to intrusion detection is effective and feasible.
摘要：
Clustering technology and boundary point detection technology and its application in intrusion detection system are introduced in this paper from three aspects, which are the application of clustering analysis, boundary detection and clustering analysis in Intrusion Detection System. The data processing and the requirement of clustering algorithm for intrusion detection system are introduced in detail. Analyzed the result of the experiment environment and experiment, further validation of this project is based on the improved NPRIM algorithm applied to intrusion detection is effective and feasible.
作者机构：
[Chen, Xin] Hunan Tradit Chinese Med Coll, Zhuzhou, Peoples R China.;[Huang, Lei] Hunan Prov Hosp Tradit Chinese Med, Zhuzhou, Peoples R China.;[Ouyang, Xinping; He, Pingping] Univ South China, Inst Cardiovascular Res, Dept Physiol, Coll Med, Hengyang, Peoples R China.;[He, Pingping] Univ South China, Sch Nursing, Hengyang, Peoples R China.;[Wang, Bo; Liao, Huiying] Univ South China, First Affiliated Hosp, Hengyang, Peoples R China.
会议名称：
International Conference on Biological Engineering and Biomedical (BEAB)
会议时间：
JAN 10-12, 2014
会议地点：
Yichang, PEOPLES R CHINA
会议主办单位：
[Huang, Lei] Hunan Prov Hosp Tradit Chinese Med, Zhuzhou, Peoples R China.^[Chen, Xin] Hunan Tradit Chinese Med Coll, Zhuzhou, Peoples R China.^[Ouyang, Xinping;He, Pingping] Univ South China, Inst Cardiovascular Res, Dept Physiol, Coll Med, Hengyang, Peoples R China.^[He, Pingping] Univ South China, Sch Nursing, Hengyang, Peoples R China.^[Wang, Bo;Liao, Huiying] Univ South China, First Affiliated Hosp, Hengyang, Peoples R China.^[Lu, Suqing] Univ Guilin Med, Affiliated Hosp, Dept Urol, Guilin, Peoples R China.^[Su, Qi] Univ South China, Dept Pathol, Hengyang, Peoples R China.
摘要：
In this study, we down-regulate the expression of calreticulin (CRT) in differentiation of human leukemic HL-60 cells induced by diallyl disulfide (DADS) so as to find out the molecular mechanism of differentiation in HL-60 cells induced by DADS. By using several methods like Giemsa's staining, siRNA, MTT, qPCR, Westenbloting, flow cytometry etc., we tested the morphology changes of HL-60 cells, detected the expression of CRT before and after the use of siRNA and DADS, also we measured the proliferation of HL-60 cells. The results showed that DADS can apparently change the morphology of HL-60, furthermore both DADS and siRNA can decrease the expression of CRT. Once CRT was silenced, the proliferation of HL-60 was inhibited in the meantime the expression of CD33 and CD11b was significantly decreased. Therefore, DADS can down-regulates CRT-induced HL-60 differentiation meanwhile the silent CRT can induce the differentiation of HL-60 cells and enhance DADS-induced HL-60 cells differentiation.
