期刊：
CURRENT CANCER DRUG TARGETS,2024年24(2):127-141 ISSN：1568-0096
通讯作者：
Zhang, ZW
作者机构：
[Huang, Xinqi] Univ South China, Hengyang Med Coll, Dept Clin Med, Grade 20, Hengyang 421001, Hunan, Peoples R China.;[Zhang, Meilan; Zhang, Zhiwei; Zhang, ZW] Univ South China, Hengyang Med Coll, Canc Res Inst, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Zhang, ZW ] U;Univ South China, Hengyang Med Coll, Canc Res Inst, Hengyang 421001, Hunan, Peoples R China.
关键词：
Apoptosis;Epstein–Barr virus-associated gastric cancer (EBVaGC);Methylation;Signaling pathway;The Latent Membrane Protein 1 (LMP1);Tumor microenvironment
摘要：
EBV promotes many cancers such as lymphoma, nasopharyngeal carcinoma, and gastric; Latent Membrane Protein 1 (LMP1) is considered to be a major oncogenic protein encoded by Epstein-Barr virus (EBV). LMP1 functions as a carcinogen in lymphoma and nasopharyngeal carcinoma, and LMP1 may also promote gastric cancer. The expression level of LMP1 in host cells is a key determinant in tumorigenesis and maintenance of virus specificity. By promoting cell immortalization and cell transformation, promoting cell proliferation, affecting immunity, and regulating cell apoptosis, LMP1 plays a crucial tumorigenic role in epithelial cancers. However, very little is currently known about LMP1 in Epstein-Barr virus-associated gastric cancer (EBVaGC); the main reason is that the expression level of LMP1 in EBVaGC is comparatively lower than other EBV-encoded proteins, such as The Latent Membrane Protein 2A (LMP2A), Epstein-Barr nuclear antigen 1 (EBNA1) and BamHI-A rightward frame 1 (BARF1), to date, there are few studies related to LMP1 in EBVaGC. Recent studies have demonstrated that LMP1 promotes EBVaGC by affecting The phosphatidylinositol 3-kinase- Akt (PI3K-Akt), Nuclear factor-kappa B (NF-κB), and other signaling pathways to regulate many downstream targets such as Forkhead box class O (FOXO), C-X-C-motif chemokine receptor (CXCR), COX-2 (Cyclooxygenase-2); moreover, the gene methylation induced by LMP1 in EBVaGC has become one of the characteristics that distinguish this gastric cancer (GC) from other types of gastric cancer and LMP1 also promotes the formation of the tumor microenvironment (TME) of EBVaGC in several ways. This review synthesizes previous relevant literature, aiming to highlight the latest findings on the mechanism of action of LMP1 in EBVaGC, summarize the function of LMP1 in EBVaGC, lay the theoretical foundation for subsequent new research on LMP1 in EBVaGC, and contribute to the development of novel LMP1-targeted drugs.
期刊：
Biochemical and Biophysical Research Communications,2024年703:149667 ISSN：0006-291X
通讯作者：
Wei, Dangheng;Wu, Peng
作者机构：
[Chen, Yanmei; Qin, Wenhua; Yu, Bo; Yuan, Chuchu] Institute of Cardiovascular Disease, Key Laboratory for Arteriosclerology of Hunan Province, Hunan International Scientific and Technological Cooperation Base of Arteriosclerotic Disease, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China;[Chen, Yanmei] Department of Pathology, Southwest Hospital, Army Medical University, Chongqing, 400038, China;[Wei, Dangheng] Institute of Cardiovascular Disease, Key Laboratory for Arteriosclerology of Hunan Province, Hunan International Scientific and Technological Cooperation Base of Arteriosclerotic Disease, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China. Electronic address: weizhonghua99@126.com;[Wu, Peng] Hengyang Maternal and Child Health Hospital, Hengyang, 421001, Hunan Province, China;[Wu, Peng] Hunan YueYang Maternal & Child Medicine Health-Care Hospital, Hunan Province Innovative Training Base for Medical Postgraduates, Yueyang, Hunan, 414000, China. Electronic address: 905595479@qq.com
通讯机构：
[Wei, Dangheng] I;[Wu, Peng] H;Institute of Cardiovascular Disease, Key Laboratory for Arteriosclerology of Hunan Province, Hunan International Scientific and Technological Cooperation Base of Arteriosclerotic Disease, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China. Electronic address:;Hunan YueYang Maternal & Child Medicine Health-Care Hospital, Hunan Province Innovative Training Base for Medical Postgraduates, Yueyang, Hunan, 414000, China. Electronic address:
摘要：
Trimethylamine N-oxide (TMAO) is a novel risk factor for atherosclerosis, and its underlying regulatory mechanisms are under intensive investigation. Inflammation-related vascular endothelial damage is the major driver in atherogenic process. Pyroptosis, a type of proinflammatory programmed cell death, has been proved to promote the initiation and progression of atherosclerosis. In our study, we found that TMAO triggered endothelial cells excessive mitophagy, thereby facilitating pyroptosis. This process is mediated by the upexpression of phosphatidylethanolamine acyltransferase (LPEAT). These findings provide insights into TMAO-induced vascular endothelial cell damage and suggest that LPEAT may be a valuable target for the prevention and treatment of atherosclerosis.
作者机构：
[Liu, Li; He, Jingzhe; Wang, Jiaren; Xiao, LS; Li, Ruining; Li, Qimei; Zeng, Lin; Liu, L; Xiao, Lushan; Li, Yan; Hong, Chang; Cui, Hao] Southern Med Univ, Nanfang Hosp, Guangdong Prov Key Lab Viral Hepatitis Res, Dept Infect Dis, Guangzhou 510515, Peoples R China.;[Ma, Pengcheng; Liu, Li; Zeng, Lin; Liu, L] Southern Med Univ, Nanfang Hosp, Big Data Ctr, Guangzhou 510515, Peoples R China.;[Zhu, Hongbo] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Med Oncol, Hengyang 421001, Hunan, Peoples R China.;[Zhu, Hong; Zhu, H] Southern Med Univ, Nanfang Hosp, Guangzhou 510515, Peoples R China.
通讯机构：
[Xiao, LS ; Liu, L ; Liu, L; Zhu, H ] S;Southern Med Univ, Nanfang Hosp, Guangdong Prov Key Lab Viral Hepatitis Res, Dept Infect Dis, Guangzhou 510515, Peoples R China.;Southern Med Univ, Nanfang Hosp, Big Data Ctr, Guangzhou 510515, Peoples R China.;Southern Med Univ, Nanfang Hosp, Guangzhou 510515, Peoples R China.
关键词：
Bone mineral density;Hepatic steatosis;Metabolic dysfunction-associated fatty liver disease;Metabolism;Osteoporosis
摘要：
Previously observational studies did not draw a clear conclusion on the association between fatty liver diseases and bone mineral density (BMD). Our large-scale studies revealed that MAFLD and hepatic steatosis had no causal effect on BMD, while some metabolic factors were correlated with BMD. The findings have important implications for the relationship between fatty liver diseases and BMD, and may help direct the clinical management of MAFLD patients who experience osteoporosis and osteopenia. PURPOSE: Liver and bone are active endocrine organs with several metabolic functions. However, the link between metabolic dysfunction-associated fatty liver disease (MAFLD) and bone mineral density (BMD) is contradictory. METHODS: Using the UK Biobank and National Health and Nutrition Examination Survey (NHANES) dataset, we investigated the association between MAFLD, steatosis, and BMD in the observational analysis. We performed genome-wide association analysis to identify single-nucleotide polymorphisms associated with MAFLD. Large-scale two-sample Mendelian randomization (TSMR) analyses examined the potential causal relationship between MAFLD, hepatic steatosis, or major comorbid metabolic factors, and BMD. RESULTS: After adjusting for demographic factors and body mass index, logistic regression analysis demonstrated a significant association between MAFLD and reduced heel BMD. However, this association disappeared after adjusting for additional metabolic factors. MAFLD was not associated with total body, femur neck, and lumbar BMD in the NHANES dataset. Magnetic resonance imaging-measured steatosis did not show significant associations with reduced total body, femur neck, and lumbar BMD in multivariate analysis. TSMR analyses indicated that MAFLD and hepatic steatosis were not associated with BMD. Among all MAFLD-related comorbid factors, overweight and type 2 diabetes showed a causal relationship with increased BMD, while waist circumference and hyperlipidemia had the opposite effect. CONCLUSION: No causal effect of MAFLD and hepatic steatosis on BMD was observed in this study, while some metabolic factors were correlated with BMD. This has important implications for understanding the relationship between fatty liver disease and BMD, which may help direct the clinical management of MAFLD patients with osteoporosis.
作者机构：
[Fu, Xiangjie; Zhou, Yiran; Pei, Siya; Wang, Yanjie; Huang, Wanting; Li, Huan; Yan, Danyang] Department of Blood Transfusion, Clinical Transfusion Research Center, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China;[Xie, Xi] Department of Clinical Laboratory, Hunan Prevention and Treatment Institute for Occupational Diseases, University of South China, Changsha, Hunan, China;[Yao, Run] Department of Blood Transfusion, Clinical Transfusion Research Center, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China. yaorunxy@csu.edu.cn;[Li, Ning] Department of Blood Transfusion, Clinical Transfusion Research Center, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China. liningxy@csu.edu.cn
摘要：
We aimed to explore the association between FFP transfusion and outcomes of DC patients with significant coagulopathy. A total of 693 DC patients with significant coagulopathy were analyzed with 233 patients per group after propensity score matching (PSM). Patients who received FFP transfusion were matched with those receiving conventional therapy via PSM. Regression analysis showed FFP transfusion had no benefit in 30-day (HR: 1.08, 95% CI 0.83-1.4), 90-day (HR: 1.03, 95% CI 0.80-1.31) and in-hospital(HR: 1.30, 95% CI 0.90-1.89) mortality, associated with increased risk of liver failure (OR: 3.00, 95% CI 1.78-5.07), kidney failure (OR: 1.90, 95% CI 1.13-3.18), coagulation failure (OR: 2.55, 95% CI 1.52-4.27), respiratory failure (OR: 1.76, 95% CI 1.15-2.69), and circulatory failure (OR: 2.15, 95% CI 1.27-3.64), and even associated with prolonged the LOS ICU (β: 2.61, 95% CI 1.59-3.62) and LOS hospital (β: 6.59, 95% CI 2.62-10.57). In sensitivity analysis, multivariate analysis (HR: 1.09, 95%CI 0.86, 1.38), IPTW (HR: 1.11, 95%CI 0.95-1.29) and CAPS (HR: 1.09, 95%CI 0.86-1.38) showed FFP transfusion had no beneficial effect on the 30-day mortality. Smooth curve fitting demonstrated the risk of liver failure, kidney failure and circulatory failure increased by 3%, 2% and 2% respectively, for each 1ml/kg increase in FFP transfusion. We found there was no significant difference of CLIF-SOFA and MELD score between the two group on day 0, 3, 7, 14. Compared with the conventional group, INR, APTT, and TBIL in the FFP transfusion group significantly increased, while PaO2/FiO2 significantly decreased within 14days. In conclusion, FFP transfusion had no beneficial effect on the 30-day, 90-day, in-hospital mortality, was associated with prolonged the LOS ICU and LOS hospital, and the increased risk of liver failure, kidney failure, coagulation failure, respiratory failure and circulatory failure events. However, large, multi-center, randomized controlled trials, prospective cohort studies and external validation are still needed to verify the efficacy of FFP transfusion in the future.
摘要：
The ribonucleic acid (RNA)-binding protein Cytoplasmic Polyadenylation Element Binding Protein 1 (CPEB1), a key member of the CPEB family, is essential in controlling gene expression involved in both healthy physiological and pathological processes. CPEB1 can bind to the 3'- untranslated regions (UTR) of substrate messenger ribonucleic acid (mRNA) and regulate its translation. There is increasing evidence that CPEB1 is closely related to the pathological basis of atherosclerosis. According to recent investigations, many pathological processes, including inflammation, lipid metabolism, endothelial dysfunction, angiogenesis, oxidative stress, cellular senescence, apoptosis, and insulin resistance, are regulated by CPEB1. This review considers the prevention and treatment of atherosclerotic heart disease in relation to the evolution of the physiological function of CPEB1, recent research breakthroughs, and the potential participation of CPEB1 in atherosclerosis.
作者机构：
[Dong, Zhao; Li, Yingji; Wang, Xiaolin; Zhang, Mingjie; Liu, Yingyuan; Zhang, Shuhua; Zhao, Wei; Su, Hui; Gong, Zihua; Han, Xun; Liu, Huanxian; Jia, Zhihua; Yu, Shengyuan; Zhai, Deqi; Sun, Yin; Liu, Ruozhuo; Ran, Ye; Lin, Xiaoxue; Xie, Siyuan] Department of Neurology, The First Medical Center of Chinese PLA General Hospital, Beijing, China. RINGGOLD: 104607;[Dong, Zhao; Li, Yingji; Wang, Xiaolin; Zhang, Mingjie; Liu, Yingyuan; Zhang, Shuhua; Zhao, Wei; Su, Hui; Gong, Zihua; Han, Xun; Liu, Huanxian; Jia, Zhihua; Zhai, Deqi; Sun, Yin; Liu, Ruozhuo; Ran, Ye; Lin, Xiaoxue; Xie, Siyuan] International Headache Centre, Chinese PLA General Hospital, Beijing, China;[Xu, Suiyi] Department of Neurology, Headache Center, The First Hospital of Shanxi Medical University, Taiyuan, Shanxi, China. RINGGOLD: 105862;[Chen, Chunfu] Department of Neurology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China;[Xue, Zhanyou] Department of Neurology, Shanghai Donglei Brain Hospital, Shanghai, China
关键词：
Cluster headache;characteristics;diagnosis;registry study;treatment status
摘要：
Cephalalgia, Volume 44, Issue 3, March 2024. <br/>BackgroundThe clinical profile of cluster headache may differ among different regions of the world, warranting interest in the data obtained from the initial Chinese Cluster Headache Register Individual Study (CHRIS) for better understanding.MethodsWe conducted a multicenter, prospective, longitudinal cohort study on cluster headache across all 31 provinces of China, aiming to gather clinical characteristics, treatment approaches, imaging, electrophysiological and biological samples.ResultsIn total 816 patients were enrolled with a male-to-female ratio of 4.33:1. The mean age at consultation was 34.98 ± 9.91 years, and 24.89 ± 9.77 years at onset. Only 2.33% were diagnosed with chronic cluster headache, and 6.99% had a family history of the condition. The most common bout was one to two times per year (45.96%), lasting two weeks to one month (44.00%), and occurring frequently in spring (76.23%) and winter (73.04%). Of these, 68.50% experienced one to two attacks per day, with the majority lasting one to two hours (45.59%). The most common time for attacks was between 9 am and 12 pm (75.86%), followed by 1 am and 3 am (43.48%). Lacrimation (78.80%) was the most predominant autonomic symptom reported. Furthermore, 39.22% of patients experienced a delay of 10 years or more in receiving a correct diagnosis. Only 35.67% and 24.26% of patients received common acute and preventive treatments, respectively.ConclusionDue to differences in ethnicity, genetics and lifestyle conditions, CHRIS has provided valuable baseline data from China. By establishing a dynamic cohort with comprehensive multidimensional data, it aims to advance the management system for cluster headache in China.
摘要：
BACKGROUND AND AIMS: Tripartite motif (TRIM65) is an important member of the TRIM protein family, which is a newly discovered E(3) ligase that interacts with and ubiquitinates various substrates and is involved in diverse pathological processes. However, the function of TRIM65 in atherosclerosis remains unarticulated. In this study, we investigated the role of TRIM65 in the pathogenesis of atherosclerosis, specifically in vascular smooth muscle cells (VSMCs) phenotype transformation, which plays a crucial role in formation of atherosclerotic lesions. METHODS AND RESULTS: Both non-atherosclerotic and atherosclerotic lesions during autopsy were collected singly or pairwise from each individual (n=16) to investigate the relationship between TRIM65 and the development of atherosclerosis. In vivo, Western diet-fed ApoE(-/-) mice overexpressing or lacking TRIM65 were used to assess the physiological function of TRIM65 on VSMCs phenotype, proliferation and atherosclerotic lesion formation. In vitro, VSMCs phenotypic transformation was induced by platelet-derived growth factor-BB (PDGF-BB). TRIM65-overexpressing or TRIM65-abrogated primary mouse aortic smooth muscle cells (MOASMCs) and human aortic smooth muscle cells (HASMCs) were used to investigate the mechanisms underlying the progression of VSMCs phenotypic transformation, proliferation and migration. Increased TRIM65 expression was detected in α-SMA-positive cells in the medial and atherosclerotic lesions of autopsy specimens. TRIM65 overexpression increased, whereas genetic knockdown of TRIM65 remarkably inhibited, atherosclerotic plaque development. Mechanistically, TRIM65 overexpression activated PI3K/Akt/mTOR signaling, resulting in the loss of the VSMCs contractile phenotype, including calponin, α-SMA, and SM22α, as well as cell proliferation and migration. However, opposite phenomena were observed when TRIM65 was deficient in vivo or in vitro. Moreover, in cultured PDGF-BB-induced TRIM65-overexpressing VSMCs, inhibition of PI3K by treatment with the inhibitor LY-294002 for 24h markedly attenuated PI3K/Akt/mTOR activation, regained the VSMCs contractile phenotype, and blocked the progression of cell proliferation and migration. CONCLUSIONS: TRIM65 overexpression enhances atherosclerosis development by promoting phenotypic transformation of VSMCs from contractile to synthetic state through activation of the PI3K/Akt/mTOR signal pathway.
摘要：
MiRNAs are small endogenous non-coding RNAs that have been demonstrated to be involved in post-transcriptional gene silencing, regulating a number of metabolic functions in the human body, including immune response, cellular physiology, organ development, angiogenesis, signaling, and other aspects. As popular molecules that have been studied in previous years, given their extensive regulatory functions, miRNAs hold considerable promise as non-invasive biomarkers. Sexually transmitted infections(STIs) are still widespread and have an adverse effect on individuals, communities, and society worldwide. miRNAs in the regulatory networks are generally involved in their molecular processes of formation and development. In this review, we discuss the value of miRNAs for the diagnosis of STIs.
作者机构：
[Ma, Pengcheng; Liang, Shengxing; Xu, Jun] Southern Med Univ, Sch Publ Hlth, Guangzhou, Peoples R China.;[Ma, Pengcheng; Li, Zeyang; Xu, Jun] Southern Med Univ, Sch Hlth Management, Guangzhou, Peoples R China.;[Ma, Pengcheng; Xu, Jun] Southern Med Univ, Nanfang Hosp, Guangzhou, Peoples R China.;[Liu, Li; He, Jingzhe; Wang, Jiaren; Li, Ruining; Zeng, Lin; Xiao, Lushan; Li, Yan; Hong, Chang; Cui, Hao] Southern Med Univ, Nanfang Hosp, Hepatol Unit, Guangdong Prov Key Lab Viral Hepatitis Res, Guangzhou, Peoples R China.;[Liu, Li; He, Jingzhe; Wang, Jiaren; Li, Ruining; Zeng, Lin; Xiao, Lushan; Li, Yan; Hong, Chang; Cui, Hao] Southern Med Univ, Nanfang Hosp, Dept Infect Dis, Guangzhou, Peoples R China.
通讯机构：
[Xiao, LS ; Xu, J ; Liu, L] S;Southern Med Univ, Nanfang Hosp, Guangzhou 510515, Peoples R China.;Southern Med Univ, Nanfang Hosp, Hepatol Unit, Guangdong Prov Key Lab Viral Hepatitis Res, Guangzhou 510515, Peoples R China.;Southern Med Univ, Nanfang Hosp, Dept Infect Dis, Guangzhou 510515, Peoples R China.
关键词：
Mendelian randomization;cholelithiasis;hand grip strength;sarcopenia;skeletal muscle index;walking pace
摘要：
Cholelithiasis is a common digestive disease that drives a myriad of adverse complications. The correlation between sarcopenia and various digestive disorders has been extensively researched, whereas its association with cholelithiasis remains unreported. We aimed to investigate the association through prospective and Mendelian randomization (MR) analyses and establish a quantitative score reflecting the impact of sarcopenia-related markers on cholelithiasis. The prospective study involved 448 627 participants from the UK Biobank. Cox proportional hazard models were employed to investigate the correlation between sarcopenia-related markers and cholelithiasis. To quantitatively assess cholelithiasis risk, the SARCHO score was derived from a multivariable Cox model. Bidirectional two-sample MR analysis was conducted to validate the causal association. A total of 16 738 individuals developed cholelithiasis during a median follow-up of 12 years. Hazard ratios (HRs) of cholelithiasis decreased stepwise over skeletal muscle index tertiles (highest tertile: reference; middle tertile: 1.23, p < .001; lowest tertile: 1.33, p < .001). The tertiles of grip strength showed a similar pattern. Individuals with slow walking pace had a higher risk of cholelithiasis compared to those with normal walking pace (HR 1.23; p < .001). Our SARCHO score better quantifies the risk of cholelithiasis. MR analysis showed a causal relationship between muscle mass and cholelithiasis (OR 0.81; p < .001). No causal effect of cholelithiasis on lean mass was observed. Prospective and MR analyses have consistently demonstrated an increased risk of cholelithiasis in individuals with decreased muscle mass. Additionally, SARCHO score further quantified the cholelithiasis occurrence risk. These findings provide compelling evidence for muscle strengthening in preventing cholelithiasis.
摘要：
Microbial degradation is a cost-effective and environmentally friendly method for removing microcystin-LR (MC-LR). However, the application of free bacteria has limitations due to low operational stability and difficulties in recovery. In a previous study, our group successfully isolated a highly efficient MC-LR-degrading bacterium, Sphingopyxis sp. YF1, from Taihu. To enhance its practical potential in addressing MC-LR-contaminated water pollution, a novel biological material named polyacrylonitrile-based carbon fiber @Sphingopyxis sp. YF1 (PAN-CF@YF1) was synthesized. The immobilization conditions of strain Sphingopyxis sp. YF1 on PAN-CF surfaces were optimized using Box–Behnken design and response surface methodology (RSM), which turned out to be an optimal pH of 7.6 for the culture medium, a ratio of 0.038 g of supporting materials per 100 mL of culture media, and an incubation time of 53.4 h. The resultant PAN-CF@YF1 showed a great degradation effect both for low and high concentrations of MC-LR and exhibited satisfactory cyclic stability (85.75% after six cycles). Moreover, the application of PAN-CF@YF1 in the bioreactors demonstrated effective and sustainable MC-LR removal, with a removal efficiency of 78.83% after three consecutive treatments. Therefore, PAN-CF@YF1 with high degradation activity, environmental compatibility, straightforward preparation, and recyclability shows significant application potential for the bioremediation of MC-LR-contaminated water bodies.
摘要：
Corticosterone (CORT) damages hippocampal neurons as well as induces neuroinflammation. The tricarboxylic acid cycle metabolite itaconate has an anti-inflammatory role. Necroptosis is a form of programmed cell death, also known as inflammatory cell death. Menin is a multifunctional scaffold protein, which deficiency aggravates neuroinflammation. In this study, we explored whether itaconate inhibits CORT-induced neuroinflammation as well as necroptosis and further investigated the mediatory role of Menin in this protective effect of itaconate by using an exposure of CORT to HT22 cells (a hippocampal neuronal cell line). The viability of HT22 cells was examined by the cell counting kit 8 (CCK-8). The morphology of HT22 cells was observed by transmission electron microscope (TEM). The expressions of necroptosis-related proteins (p-RIP1/RIP1, p-RIP3/RIP3, and p-MLKL/MLKL) were evaluated by western blotting. The contents of inflammatory factors were detected by an enzyme-linked immunosorbent assay (ELISA) kit. Our results showed that CORT increases the contents of pro-inflammatory factors (IL-1β, TNF-α) as well as decreases the contents of anti-inflammatory factors (IL-4, IL-10) in HT22 cells. We also found that CORT increases the expressions of necroptosis-related proteins (p-RIP1/RIP1, p-RIP3/RIP3, and p-MLKL/MLKL) and decreases the cell viability in HT22 cells, indicating that CORT induces necroptosis in HT22 cells. Itaconate improves CORT-induced neuroinflammation and necroptosis. Furthermore, itaconate upregulates the expression of Menin in CORT-exposed HT22 cells. Importantly, silencing Menin abolishes the antagonistic effect of itaconate on CORT-induced necroptosis and neuroinflammation. In brief, these results indicated that itaconate protects HT22 cells against CORT-induced neuroinflammation and necroptosis via upregulating Menin.
摘要：
Abnormal activation of macrophage and gut Bacteroides fragilis (BF) are the important induction factors in the occurrence of type 2 diabetes (T2D) and vascular complications. However, it remains unknown whether BF involves in macrophage polarization. In this study, we found that BF extracellular vesicles (EV) can be uptaken by macrophage. BF-EV promote macrophage M1/M2 polarization significantly, and increase Sting expression significantly. Bioinformatics analysis found that Sema7a is an important gene involving in macrophage polarization. The expression of Sema7a can be induced by BF-EV and can be inhibited after C-176 treated. The inhibition expression of Sema7a prevent BF-EV to induce macrophage polarization. Further analysis reveals that there is no direct interaction between Sting and Sema7a, but Sgpl1 can interact with Sting or Sema7a. BF-EV promote the expression of Sgpl1, which the phenomenon can be inhibited after C-176 treated. Importantly, overexpression of Sgpl1 reversed the effect of C-176 for Sema7a expression, while inhibit Sema7a expression has limitation influence for Sting and Sgpl1 expression. In conclusion, this study confirms that Sting-Sgpl1-Sema7a is a key mechanism by which BF-EV regulates macrophage polarization.
期刊：
Indian Journal of Hematology and Blood Transfusion,2024年:1-10 ISSN：0971-4502
通讯作者：
Deng, J
作者机构：
[Li, Yike] Hunan Normal Univ, Changsha Hosp Maternal & Child Hlth Care, Dept Clin Lab, Changsha 410007, Hunan, Peoples R China.;[Deng, Jun] Univ South China, Affiliated Changsha Cent Hosp, Hengyang Med Sch, Dept Clin Lab, Changsha 410004, Hunan, Peoples R China.
通讯机构：
[Deng, J ] U;Univ South China, Affiliated Changsha Cent Hosp, Hengyang Med Sch, Dept Clin Lab, Changsha 410004, Hunan, Peoples R China.
关键词：
ABO hemolytic disease of the newborn;L score;Differential diagnosis;Blood routine examination;Early diagnosis
摘要：
Purpose This study aimed to evaluate the diagnostic efficacy of the L score, a novel scoring system, in distinguishing between ABO hemolytic disease of the newborn (ABO-HDN) and non-hemolytic disease of newborn hyperbilirubinemia (NHDNH).Methods A cross-sectional prospective study was conducted to assess the effectiveness of the L score in distinguishing between ABO-HDN (n = 118) and NHDNH (n = 213). Blood routine examination results were collected, and relevant statistical analyses were performed to identify clinically significant parameters. Binary logistic regression analysis was employed to assess the relationship between the L score and the development of these conditions, considering relevant variables.Results Our study identified the red blood cell count, mean corpuscular volume, red blood cell distribution width-coefficient of variation, and red blood cell distribution width-standard deviation as independent risk factors for distinguishing ABO-HDN from other high bilirubinemia conditions (P < 0.001). The L score demonstrated superior predictive performance for ABO-HDN, exhibiting an area under the curve (AUC) of 0.746, with an optimal cutoff value of - 3.0816. The RBC-L score exhibited superior predictive performance (z: 5.596, P < 0.0001) compared to the single-factor RBC indicator, indicating its efficacy in accurately identifying the desired outcome.Conclusion The L score represents a valuable tool for predicting neonatal hyperbilirubinemia and hemolytic disease, facilitating differentiation, and guiding early intervention for improved outcomes. Further research is warranted to validate and expand the applicability of the L score in clinical practice.
作者机构：
[Wang, Biao; Yuan, Mei; He, Caijun; Chen, Sisi; Liu, Xiaofen; Zhang, Wentao; Ding, Yingmei; Ma, Bin] The Second Affiliated Hospital, Department of Neurology, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China;[Yuan, Mei] Affiliated Nanhua Hospital, Department of Neurology, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China
关键词：
Molecular biology;Physiology
摘要：
Blood-brain barrier (BBB) disruption following ischemic stroke (IS) can induce significant aftereffects. Elevated calmodulin (CaM) expression following stroke causes calcium overload-a key contributor to BBB collapse. Trifluoperazine (TFP), a CaM inhibitor, reduces CaM overexpression following IS. However, it remains unclear whether TFP participates in BBB repair after IS. We administered TFP to mice subjected to middle cerebral artery occlusion (MCAO) and bEnd.3 cells subjected to oxygen-glucose deprivation (OGD). TFP treatment in MCAO mice reduced cerebral CaM expression and infarct size and decreased BBB permeability. OGD-treated bEnd.3 cells showed significantly increased CaM protein levels and reduced tight junction (TJ) protein levels; these changes were reversed by TFP treatment. Our results found that TFP administration in mice inhibited actin contraction following cerebral ischemia-reperfusion by suppressing the MLCK/p-MLC pathway, thereby attenuating cell retraction, improving TJ protein integrity, and reducing BBB permeability. Consequently, this treatment may promote neurological function recovery after IS.
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.
期刊：
JOURNAL OF INFECTIOUS DISEASES,2024年 ISSN：0022-1899
通讯作者：
Qu, XW
作者机构：
[Zheng, Xingyu; Liu, Fen; Qu, Xiaowang; Wu, Chanfeng; Lu, Rui; Xie, Tianyi; Liu, Wenpei] Univ South China, Coll Basic Med, Hengyang Med Sch, Hengyang, Peoples R China.;[Zheng, Xingyu; Chen, Jun; Wang, You; Liu, Fen; Tang, Jinyong; Pan, Dong; Tang, Yinggen; Wu, Chanfeng; Teng, Shishan; Peng, Liting; Lu, Rui; He, Rongzhang; Hu, Yabin; Rong, Xiaohan; Xie, Tianyi] Univ South China, Peoples Hosp Chenzhou 1, Translat Med Inst, Hengyang Med Sch, Chenzhou, Peoples R China.;[Wang, You] Univ South China, Sch Publ Hlth, Hengyang, Peoples R China.;[Qu, Xiaowang] Univ South China, Coll Basic Med, Hengyang Med Sch, 28 West Changsheng Rd, Hengyang 421001, Peoples R China.
通讯机构：
[Qu, XW ] U;Univ South China, Coll Basic Med, Hengyang Med Sch, 28 West Changsheng Rd, Hengyang 421001, Peoples R China.
关键词：
COVID-19;Circulating T-Follicular Helper Cell;Neutralizing Antibody;Regulatory T cell
摘要：
Regulatory T (Treg) cells are involved in the antiviral immune response in patients with coronavirus disease 2019 (COVID-19); however, whether Treg cells are involved in the neutralizing antibody (nAb) response remains unclear. Here, we found that individuals who recovered from mild but not severe COVID-19 had significantly greater frequencies of Treg cells and lower frequencies of CXCR3+ circulating T follicular helper (cTfh) cells than healthy controls. Furthermore, the frequencies of Treg and CXCR3+ cTfh cells were negatively and positively correlated with the nAb responses, respectively, and Treg cells was inversely associated with CXCR3+ cTfh cells in individuals who recovered from mild COVID-19 but not in those with severe disease. Mechanistically, Treg cells inhibited memory B-cell differentiation and antibody production by limiting the activation and proliferation of cTfh cells, especially CXCR3+ cTfh cells, and functional molecule expression. This study provides novel insight showing that mild COVID-19 elicits concerted nAb responses, which are shaped by both Treg and Tfh cells.
摘要：
BACKGROUND: With cancer-associated fibroblasts (CAFs) as the main cell type, the rich myxoid stromal components in chordoma tissues may likely contribute to its development and progression. METHODS: Single-cell RNA sequencing (scRNA-seq), spatial transcriptomics, bulk RNA-seq, and multiplexed quantitative immunofluorescence (QIF) were used to dissect the heterogeneity, spatial distribution, and clinical implication of CAFs in chordoma. RESULTS: We sequenced here 72 097 single cells from 3 primary and 3 recurrent tumor samples, as well as 3 nucleus pulposus samples as controls using scRNA-seq. We identified a unique cluster of CAF in recurrent tumors that highly expressed hypoxic genes and was functionally enriched in endoplasmic reticulum stress (ERS). Pseudotime trajectory and cell communication analyses showed that this ERS-CAF subpopulation originated from normal fibroblasts and widely interacted with tumoral and immune cells. Analyzing the bulk RNA-seq data from 126 patients, we found that the ERS-CAF signature score was associated with the invasion and poor prognosis of chordoma. By integrating the results of scRNA-seq with spatial transcriptomics, we demonstrated the existence of ERS-CAF in chordoma tissues and revealed that this CAF subtype displayed the most proximity to its surrounding tumor cells. In subsequent QIF validation involving 105 additional patients, we confirmed that ERS-CAF was abundant in the chordoma microenvironment and located close to tumor cells. Furthermore, both ERS-CAF density and its distance to tumor cells were correlated with tumor malignant phenotype and adverse patient outcomes. CONCLUSIONS: These findings depict the CAF landscape for chordoma and may provide insights into the development of novel treatment approaches.
作者机构：
[Zhang, Jing; He, Rongfang; Li, Jianping; Li, JP; Lan, Zhihua] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Pathol, Hengyang, Peoples R China.
通讯机构：
[Li, JP ] U;Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Pathol, Hengyang, Peoples R China.
关键词：
axillary lymph node;breast cancer patients;fine-needle aspiration;GATA-3 immunocytochemistry
摘要：
BACKGROUND: Ultrasound-guided fine-needle aspiration cytology (FNAC) is a routine preoperative method for evaluating suspicious axillary lymph nodes (ALNs) in patients with breast cancer. However, a range of reasons such as morphological pitfalls, technical artifacts, and sampling errors restrict the sensitivity and accuracy of FNAC. This retrospective study investigated the diagnostic value of GATA-binding protein 3 (GATA-3) immunocytochemistry for FNAC. METHODS: Breast cancer patients who underwent preoperative FNAC for suspicious ALNs, relevant GATA-3 immunocytochemistry, and postoperative status of ALNs were reviewed from the period of March 2020 to February 2022. Altogether, 102 patients were included in the study. FNAC material smears stained with hematoxylin and eosin was initially assessed by two cytopathologists and categorized into five groups: nondiagnostic, negative, atypical, suspicious, and positive for malignancy. Only group of cells positive for malignancy was considered positive. For each case, two selected slides were digitized (whole slide imaged) at ×40 magnification and decolored for GATA-3 immunocytochemistry. The expression of GATA-3 was scored ranging from 0 to 9 (Score ≥3: Positive, Score ≤2: Negative). If either FNAC or GATA-3 immunocytochemistry was positive or the combined test positive, then the case was considered positive. The sensitivity, specificity, and accuracy of FNAC, GATA-3 immunocytochemistry, and combined FNAC/GATA-3 immunocytochemistry were analyzed by χ(2) and Fisher's tests. RESULTS: The mean age of the study participants was 50.62 (ranging: 30-73 years). Invasive breast carcinoma (not otherwise specified) accounted for most histological subtypes, and grade 2 was the leading Nottingham grade. Sixteen cases directly underwent mastectomy while the other 86 patients had neoadjuvant therapy. A more serious diagnosis was made based on GATA-3 detection in 22.5% (n = 23) of 102 cases. Of the 23 cases, metastasis was confirmed by GATA-3 detection in 21 cases, and an uncertain diagnosis was ascertained based on GATA-3 immunocytochemistry in 2 with nondiagnostic FNAC results. The sensitivity (77/87, 88.5%) of GATA-3 detection for distinguishing malignancies from benign lesions was higher than that of FNAC alone (62/87, 71.3%) (p < .05). CONCLUSIONS: GATA-3 immunocytochemistry exhibited high diagnostic efficacy in distinguishing malignant breast cancer cells. Moreover, combined FNAC and GATA-3 immunocytochemistry achieved optimal results in terms of reducing the false-negative rate and promoting accuracy.
