摘要：
Exosomes secreted from cells carry rich information from their parent cells, representing a promising biomarker for investigation of diseases. We develop a dual-nanopore biosensor using DNA aptamers to specifically recognize CD63 protein on the exosome's surface, which enables label-free exosome detection based on ionic current change. The sensor allows for sensitive detection of exosomes with a detection limit of 3.4 × 10(6) particles/mL. The dual-nanopore biosensor was able to form an intrapipette electric circuit for ionic current measurement due to its unique structure, which is crucial to achieve detection of exosome secretion from a single cell. We utilized a microwell array chip to entrap a single cell into a confined microwell with small volume, enabling the accumulation of exosomes with high concentration. The dual-nanopore biosensor was positioned into the microwell with a single cell, and monitoring of exosome secretion from a single cell in different cell lines and under different stimulations has been achieved. Our design may provide a useful platform for developing nanopore biosensors for detecting cell secretions from a single living cell.
摘要：
Angiopoietin4(ANGPT4) which plays a significant role in endothelial cell proliferation, survival, angiogenesis and expansion in tumors and other pathological states is a significant regulator of tumor angiogenesis. ANGPT4 expression is enhanced in many cancer cells. For example, the overexpression of ANGPT4 promotes the formation, development and progress of lung adenocarcinoma, glioblastoma and ovarian cancer. Related studies show that ANGPT4 encourages the proliferation, survival and invasion of tumor cells, while promoting the expansion of the tumor vascular system and affecting the tumor immune microenvironment. ANGPT4 can also promote carcinogenesis by affecting the ERK1/2, PI3K/AKT and other signal pathways downstream of tyrosine kinase with immunoglobulin-like and EGF-like domains 2(TIE2) and TIE2. Therefore, ANGPT4 may be a potential and significant biomarker for predicting malignant tumor progression and adverse outcomes. In addition, inhibition of ANGPT4 may be a meaningful cancer treatment. This paper reviews the latest research results of ANGPT4 in preclinical research, and emphasizes its role in carcinogenesis. Additional research on the carcinogenic function of ANGPT4 could provide new insights into cancer biology and novel methods for cancer diagnosis and treatment.
作者机构：
[Gao, Rong; Ren, Zhong; He, Nai-qi; Zhao, Yi-meng; Xu, Qian; Xu, Wen-xin; Zhuo, Xiu-juan; Liu, Lu-shan] Univ South China, Inst Cardiovasc Dis, Hengyang Med Coll, Key Lab Arteriosclerol Hunan Prov Hunan Int Sci &, Hengyang 421001, Hunan, Peoples R China.;[Wu, Chun-yan] Univ South China, Affiliated Hosp 3, Dept Cardiovasc Med, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Chun-yan Wu] T;[Lu-shan Liu] I;The Third Affiliated Hospital, Department of Cardiovascular Medicine, University of South China, Hengyang, Hunan Province 421001, PR China<&wdkj&>Institute of Cardiovascular Disease, Key Laboratory for Arteriosclerology of Hunan Province, Hunan International Scientific and Technological Cooperation Base of Arteriosclerotic Disease, Hengyang Medical College, University of South China, Hengyang, Hunan Province 421001, PR China
摘要：
Heart failure (HF) is a complex clinical syndrome caused by various cardiovascular diseases. Its main pathogenesis includes cardiomyocyte loss, myocardial energy metabolism disorder, and activation of cardiac inflammation. Due to the clinically unsatisfactory treatment of heart failure, different mechanisms need to be explored to provide new targets for the treatment of this disease. Proprotein convertase subtilisin/kexin type 9 (PCSK9), a gene mainly related to familial hypercholesterolemia, was discovered in 2003. Aside from regulating lipid metabolism, PCSK9 may be involved in other biological processes such as apoptosis, autophagy, pyroptosis, inflammation, and tumor immunity and related to diabetes and neurodegenerative diseases. Recently, clinical data have shown that the circulating PCSK9 level is significantly increased in patients with heart failure, and it is related to the prognosis for heart failure. Furthermore, in animal models and patients with myocardial infarction, PCSK9 in the infarct margin area was also found to be significantly increased, which further suggested that PCSK9 might be closely related to heart failure. However, the specific mechanism of how PCSK9 participates in heart failure remains to be further explored. The purpose of this review is to summarize the potential mechanism of PCSK9's involvement in heart failure, thereby providing a new treatment strategy for heart failure.
摘要：
The oldest known highly conserved modification of RNA, N4-acetylcytidine, is widely distributed from archaea to eukaryotes and acts as a posttranscriptional chemical modification of RNA, contributing to the correct reading of specific nucleotide sequences during translation, stabilising mRNA and improving transcription efficiency. Yeast Kre33 and human NAT10, the only known authors of ac4C, modify tRNA with the help of the Tan1/THUMPD1 adapter to stabilise its structure. Currently, the mRNA for N4-acetylcytidine (ac4C), catalysed by NAT10 (N-acetyltransferase 10), has been implicated in a variety of human diseases, particularly cancer. This article reviews advances in the study of ac4C modification of RNA and the ac4C-related gene NAT10 in normal physiological cell development, cancer, premature disease and viral infection and discusses its therapeutic promise and future research challenges.
期刊：
Cancer Gene Therapy,2023年30(5):659-670 ISSN：0929-1903
通讯作者：
Yang, J.;Wang, J.
作者机构：
[Liu, Zhifeng] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Otorhinolaryngol, Hengyang 421001, Hunan, Peoples R China.;[Zhang, Xin; Liu, Zhifeng; Wang, Juncheng] Cent South Univ, Xiangya Hosp, Dept Otolaryngol Head & Neck Surg, Changsha 410008, Hunan, Peoples R China.;[Zhang, Xin; Liu, Zhifeng; Wang, Juncheng] Otolaryngolgy Major Dis Res Key Hunan Prov, Changsha 410008, Hunan, Peoples R China.;[Zhang, Xin; Liu, Zhifeng; Wang, Juncheng; Tian, Yuxi] Xiangya Hosp, Natl Clin Res Ctr Geriatr Disorders, Changsha 410008, Hunan, Peoples R China.;[Tian, Yuxi] Cent South Univ, Xiangya Hosp, Dept Geriatr, Resp Med, Changsha 410008, Hunan, Peoples R China.
通讯机构：
[Juncheng Wang] D;[Jing Yang] T;Department of Otolaryngology, Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, People’s Republic of China<&wdkj&>Otolaryngolgy Major Disease Research Key of Hunan Province, Changsha, People’s Republic of China<&wdkj&>National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, People’s Republic of China<&wdkj&>The First Affiliated Hospital, Department of Gastroenterology, Hengyang Medical School, University of South China, Hengyang, People’s Republic of China<&wdkj&>Cancer Research Institute, Hunan Province Key Laboratory of Tumor Cellular & Molecular Pathology, University of South China, Hengyang, People’s Republic of China
摘要：
The genes that control drug absorption, distribution, metabolism, and excretion (ADME) are also involved in carcinogenesis, cancer progression, and chemoresistance. However, no studies have systematically investigated the clinical significance and underlying functions of ADME genes in head and neck squamous cell carcinoma. Herein, we comprehensively explored the ADME genes in this disease, constructed and validated as a prognostic ADME gene signature (ADMEGS), using three ADME genes (ABCB1, ALDH1B1, and PON2) utilizing multiple datasets, including the training and test sets of The Cancer Genome Atlas and the Gene Expression Omnibus validation set. Moreover, we analyzed the relationship between the ADMEGS and clinical parameters, tumor immunity, and therapeutic response. We found that the ADMEGS was significantly correlated with the clinical, T, and N stages. Additionally, we were able to effectively differentiate tumor immune scores, immune cell infiltration statuses, and treatment responses based on the ADMEGS. As such, ADMEGS may be promising predictors for clinical outcome, tumor immunity, and treatment response.
作者机构：
[Peng, Jianchun; Dai, Yueli; Cao, Yi] Univ South China, Affiliated Hosp 2, Hengyang Med Sch, Dept Radiol, Hengyang, Hunan, Peoples R China.;[Zhou, Hong; Ouyang, Chenyu; Luo, Guanghua] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Radiol, Hengyang, Hunan, Peoples R China.;[Gao, AB; Gao, Anbo] Univ South China, Affiliated Hosp 2, Clin Res Inst, Hengyang Med Sch, Hengyang, Hunan, Peoples R China.;[Gao, AB; Gao, Anbo] Univ South China, Affiliated Hosp 2, Hengyang Med Sch, Dept Cardiovasc Med, Hengyang, Hunan, Peoples R China.;[Gao, AB; Gao, Anbo] Clin Med Res Ctr Arteriosclerot Dis Hunan Prov, Key Lab Heart Failure Prevent & Treatment Hengyang, Hengyang, Hunan, Peoples R China.
通讯机构：
[Zhou, H ; Gao, AB ] U;Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Radiol, Hengyang, Hunan, Peoples R China.;Univ South China, Affiliated Hosp 2, Clin Res Inst, Hengyang Med Sch, Hengyang, Hunan, Peoples R China.;Univ South China, Affiliated Hosp 2, Hengyang Med Sch, Dept Cardiovasc Med, Hengyang, Hunan, Peoples R China.;Clin Med Res Ctr Arteriosclerot Dis Hunan Prov, Key Lab Heart Failure Prevent & Treatment Hengyang, Hengyang, Hunan, Peoples R China.
摘要：
OBJECTIVE: This study aimed to investigate a variety of machine learning (ML) methods to predict the association between cardiovascular risk factors and coronary artery disease-reporting and data system (CAD-RADS) scores. METHODS: This is a retrospective cohort study. Demographical, cardiovascular risk factors and coronary CT angiography (CCTA) characteristics of the patients were obtained. Coronary artery disease (CAD) was evaluated using CAD-RADS score. The stenosis severity component of the CAD-RADS was stratified into two groups: CAD-RADS score 0-2 group and CAD-RADS score 3-5 group. CAD-RADS scores were predicted with random forest (RF), k-nearest neighbors (KNN), support vector machines (SVM), neural network (NN), decision tree classification (DTC) and linear discriminant analysis (LDA). Prediction sensitivity, specificity, accuracy and area under the curve (AUC) were calculated. Feature importance analysis was utilized to find the most important predictors. RESULTS: A total of 442 CAD patients with CCTA examinations were included in this study. 234 (52.9%) subjects were CAD-RADS score 0-2 group and 208 (47.1%) were CAD-RADS score 3-5 group. CAD-RADS score 3-5 group had a high prevalence of hypertension (66.8%), hyperlipidemia (50%) and diabetes mellitus (DM) (35.1%). Age, systolic blood pressure (SBP), mean arterial pressure, pulse pressure, pulse pressure index, plasma fibrinogen, uric acid and blood urea nitrogen were significantly higher (p<0.001), and high-density lipoprotein (HDL-C) lower (p<0.001) in CAD-RADS score 3-5 group compared to the CAD-RADS score 0-2 group. Nineteen features were chosen to train the models. RF (AUC = 0.832) and LDA (AUC = 0.81) outperformed SVM (AUC = 0.772), NN (AUC = 0.773), DTC (AUC = 0.682), KNN (AUC = 0.707). Feature importance analysis indicated that plasma fibrinogen, age and DM contributed most to CAD-RADS scores. CONCLUSION: ML algorithms are capable of predicting the correlation between cardiovascular risk factors and CAD-RADS scores with high accuracy.
期刊：
Brain and Behavior,2023年13(5):e2935- ISSN：2162-3279
通讯作者：
Peng Cao<&wdkj&>Peng Cao Peng Cao Peng Cao
作者机构：
[Chen, Yanfang] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Neurol, Hengyang, Peoples R China.;[Cao, Peng] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Hepatopancreatobiliary Surg, 69 Chuanshan Ave, Hengyang 421001, Peoples R China.
通讯机构：
[Peng Cao; Peng Cao Peng Cao Peng Cao] T;The First Affiliated Hospital, Department of Hepatopancreatobiliary Surgery, Hengyang Medical School, University of South China, Hengyang, China
作者机构：
[Li, Nan-Ping; Zhang, Jing; Wang, Ai-Ping; Luo, Meng-Yi; Wang, Di] Univ South China, Inst Neurosci Res, Hengyang Med Sch, Dept Physiol, Hengyang 421001, Hunan, Peoples R China.;[Gong, Shao-Xin; Gong, SX] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Pathol, Hengyang 421001, Hunan, Peoples R China.;[Wang, Ai-Ping; Tian, Ying; Luo, Meng-Yi] Univ South China, Affiliated Nanhua Hosp, Inst Clin Res, Hengyang Med SchDept Clin Lab, Hengyang 421002, Hunan, Peoples R China.;[Li, Nan-Ping; Liang, Na] Univ South China, Affiliated Nanhua Hosp, Hengyang Med Sch, Dept Anesthesiol, Hengyang 421002, Hunan, Peoples R China.
通讯机构：
[Wang, AP ; Gong, SX ] U;Univ South China, Inst Neurosci Res, Hengyang Med Sch, Dept Physiol, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Pathol, Hengyang 421001, Hunan, Peoples R China.
关键词：
Class of effect;Pulmonary hypertension;Vascular remodeling;miRNAs
摘要：
Pulmonary hypertension (PH) is complex disease as a result of obstructive pulmonary arterial remodeling, which in turn results in elevated pulmonary arterial pressure (PAP) and subsequent right ventricular heart failure, eventually leading to premature death. However, there is still a lack of a diagnostic blood-based biomarker and therapeutic target for PH. Because of the difficulty of diagnosis, new and more easily accessible prevention and treatment strategy are being explored. New target and diagnosis biomarkers should also allow for early diagnosis. In biology, miRNAs are short endogenous RNA molecules that are not coding. It is known that miRNAs can regulate gene expression and affect a variety of biological processes. Besides, miRNAs have been proven to be a crucial factor in PH pathogenesis. miRNAs have various effects on pulmonary vascular remodeling and are expressed differentially in various pulmonary vascular cells. Nowadays, it has been shown to be critical in the functions of different miRNAs in the pathogenesis of PH. Therefore, clarifying the mechanism of miRNAs regulating pulmonary vascular remodeling is of great importance to explore new therapeutic targets of PH and improve the survival qualify and time of patients. This review is focused on the role, mechanism, and potential therapeutic targets of miRNAs in PH and puts forward possible clinical treatment strategies.
摘要：
Treatment of Klebsiella pneumoniae causing pyogenic infections is challenging. The clinical and molecular characteristics of Klebsiella pneumoniae causing pyogenic infections are poorly understood, and antibacterial treatment strategies are limited. We analyzed the clinical and molecular characteristics of K. pneumoniae from patients with pyogenic infections and used time-kill assays to reveal the bactericidal kinetics of antimicrobial agents against hypervirulent K. pneumoniae (hvKp). A total of 54 K. pneumoniae isolates were included, comprising 33 hvKp and 21 classic K. pneumoniae (cKp) isolates, and the hvKp and cKp isolates were identified using five genes (iroB, iucA, rmpA, rmpA2, and peg-344) that have been applied as hvKp strain markers. The median age of all cases was 54 years (25th and 75th percentiles, 50.5 to 70), 62.96% of individuals had diabetes, and 22.22% of isolates were sourced from individuals without underlying disease. The ratios of white blood cells/procalcitonin and C-reactive protein/procalcitonin were potential clinical markers for the identification of suppurative infection caused by hvKp and cKp. The 54 K. pneumoniae isolates were classified into 8 sequence type 11 (ST11) and 46 non-ST11 strains. ST11 strains carrying multiple drug resistance genes have a multidrug resistance phenotype, while non-ST11 strains carrying only intrinsic resistance genes are generally susceptible to antibiotics. Bactericidal kinetics revealed that hvKp isolates were not easily killed by antimicrobials at susceptible breakpoint concentrations compared with cKp. Given the varied clinical and molecular features and the catastrophic pathogenicity of K. pneumoniae, it is critical to determine the characteristics of such isolates for optimal management and effective treatment of K. pneumoniae causing pyogenic infections.IMPORTANCE Klebsiella pneumoniae may cause pyogenic infections, which are potentially life-threatening and bring great challenges for clinical management. However, the clinical and molecular characteristics of K. pneumoniae are poorly understood, and effective antibacterial treatment strategies are limited. We analyzed the clinical and molecular features of 54 isolates from patients with various pyogenic infections. We found that most patients with pyogenic infections had underlying diseases, such as diabetes. The ratio of white blood cells to procalcitonin and the ratio of C-reactive protein to procalcitonin were potential clinical markers for differentiating hypervirulent K. pneumoniae strains from classical K. pneumoniae strains that cause pyogenic infections. K. pneumoniae isolates of ST11 were generally more resistant to antibiotics than non-ST11 isolates. Most importantly, hypervirulent K. pneumoniae strains were more tolerant to antibiotics than classic K. pneumoniae isolates. Klebsiella pneumoniae may cause pyogenic infections, which are potentially life-threatening and bring great challenges for clinical management. However, the clinical and molecular characteristics of K. pneumoniae are poorly understood, and effective antibacterial treatment strategies are limited.
作者机构：
[Zhang, Wendiao; Liu, Chunyu; Chen, C; Chen, Chao; Zhang, Ming] Cent South Univ, Xiangya Hosp 2, Ctr Med Genet, Changsha 410008, Hunan, Peoples R China.;[Zhang, Wendiao; Liu, Chunyu; Chen, C; Chen, Chao; Zhang, Ming] Cent South Univ, Xiangya Hosp 2, Sch Life Sci, Hunan Key Lab Med Genet, Changsha 410008, Hunan, Peoples R China.;[Zhang, Wendiao; Liu, Chunyu; Chen, C; Chen, Chao; Zhang, Ming] Cent South Univ, Xiangya Hosp 2, Dept Psychiat, Changsha 410008, Hunan, Peoples R China.;[Meng, Qingtuan; Zhang, Wendiao; Yan, Hongye; Tang, Beisha; Xu, Zhenhong; Jiang, Jiamei; Wan, Juan; Wang, Huimin] Univ South China, Affiliated Hosp 1, Multiom Res Ctr Brain Disorders, Hengyang Med Sch, Hengyang 421000, Hunan, Peoples R China.;[Meng, Qingtuan; Zhang, Wendiao; Yan, Hongye; Tang, Beisha; Xu, Zhenhong; Jiang, Jiamei; Wan, Juan; Wang, Huimin] Univ South China, Affiliated Hosp 1, Clin Res Ctr Immune Related Encephalopathy Hunan P, Hengyang Med Sch, Hengyang 421000, Hunan, Peoples R China.
通讯机构：
[Meng, QT ] U;[Liu, CY ] S;[Liu, CY; Chen, C ] C;Cent South Univ, Xiangya Hosp 2, Ctr Med Genet, Changsha 410008, Hunan, Peoples R China.;Cent South Univ, Xiangya Hosp 2, Sch Life Sci, Hunan Key Lab Med Genet, Changsha 410008, Hunan, Peoples R China.
摘要：
Identifying genes whose expression is associated with schizophrenia (SCZ) risk by transcriptome-wide association studies (TWAS) facilitates downstream experimental studies. Here, we integrated multiple published datasets of TWAS, gene coexpression, and differential gene expression analysis to prioritize SCZ candidate genes for functional study. Convergent evidence prioritized Propionyl-CoA Carboxylase Subunit Beta (PCCB), a nuclear-encoded mitochondrial gene, as an SCZ risk gene. However, the PCCB’s contribution to SCZ risk has not been investigated before. Using dual luciferase reporter assay, we identified that SCZ-associated SNPs rs6791142 and rs35874192, two eQTL SNPs for PCCB, showed differential allelic effects on transcriptional activities. PCCB knockdown in human forebrain organoids (hFOs) followed by RNA sequencing analysis revealed dysregulation of genes enriched with multiple neuronal functions including gamma-aminobutyric acid (GABA)-ergic synapse. The metabolomic and mitochondrial function analyses confirmed the decreased GABA levels resulted from inhibited tricarboxylic acid cycle in PCCB knockdown hFOs. Multielectrode array recording analysis showed that PCCB knockdown in hFOs resulted into SCZ-related phenotypes including hyper-neuroactivities and decreased synchronization of neural network. In summary, this study utilized hFOs-based multi-omics analyses and revealed that PCCB downregulation may contribute to SCZ risk through regulating GABAergic pathways, highlighting the mitochondrial function in SCZ. Identifying schizophrenia risk genes is essential for illuminating the disease etiology. Here, authors prioritized Propionyl-CoA Carboxylase Subunit Beta (PCCB) as a schizophrenia-associated gene, and linked PCCB to GABAergic pathways using human forebrain organoids-based transcriptomic and metabolomic analysis.
作者机构：
[Peng, Hong; Liu, Zhifeng; Gong, Yongqian; Jiang, Qingshan; Liu, Lijun; Liao, Qingyun; Wang, Qin] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Otolaryngol, Hengyang, Hunan, Peoples R China.;[Yang, Jing] Univ South China, Canc Res Inst, Hunan Prov Key Lab Tumor Cellular & Mol Pathol, Hengyang, Hunan, Peoples R China.;[Yang, Jing] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Gastroenterol, Hengyang, Hunan, Peoples R China.;[Zhang, Xin; Lu, Zhaoyi] Cent South Univ, Key Lab Hunan Prov, Otolaryngol Major Dis Res, Changsha, Hunan, Peoples R China.
通讯机构：
[Liu, ZF ] U;Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Otolaryngol, Hengyang, Hunan, Peoples R China.
关键词：
Biomarker;FTH1 (ferritin heavy chain);HNSCC (head and neck squamous cell carcinoma);Metastasis;Prognosis
摘要：
BACKGROUND: Currently, ferritin heavy chain (FTH1) has been increasingly found to play a crucial role in cancer as a core regulator of ferroptosis, while its role of non-ferroptosis in head and neck squamous cell carcinoma (HNSCC) is still unclear. METHODS: Herein, we analyzed the expression level of FTH1 in HNSCC using TCGA database, and FTH1 protein in HNSCC tissues and cell lines was determined by immunohistochemistry (IHC) and western blotting, respectively. Then, its prognostic value and relationship with clinical parameters were investigated in HNSCC patients. Additionally, the biological function of FTH1 in HNSCC was explored. RESULTS: The current study showed that FTH1 is significantly overexpressed in HNSCC tissues and related to poor prognosis and lymph node metastasis of HNSCC. FTH1 knockdown could suppress the metastasis and epithelial-mesenchymal transition (EMT) process of HNSCC. CONCLUSION: Our findings indicate that FTH1 plays a critical role in the progression and metastasis of HNSCC and can serve as a promising prognostic factor and therapeutic target in HNSCC.
期刊：
International Immunopharmacology,2023年117:110006 ISSN：1567-5769
通讯作者：
Fengrui Yang
作者机构：
[Liu, Xinxin; Yang, Fengrui] First Peoples Hosp Huaihua, Dept Anesthesiol, Huaihua 418000, Peoples R China.;[Tang, Wenqiang; Qin, Jie; Chen, Kemin; Yang, Fengrui; Wang, Yuxia] Univ South China, Affiliated Hosp 1, Dept Anesthesiol, Hengyang 421001, Peoples R China.;[Yang, Fengrui] First Peoples Hosp Huaihua, Dept Anesthesiol, 144,Jinxi South Rd, Huaihua 418000, Hunan, Peoples R China.
通讯机构：
[Fengrui Yang] D;Department of Anesthesiology, The First People’s Hospital of Huaihua, Huaihua 418000, PR China<&wdkj&>Department of Anesthesiology, The First Affiliated Hospital of University of South China, Hengyang 421001, PR China
摘要：
INTRODUCTION: Novel mechanistic insights into the effects of circular RNAs (circRNAs) on the physiology and pathology of cardiovascular diseases are under increasingly active investigation. This study defined the cardioprotective role and mechanistic actions of circ_0002612 in myocardial ischemia/reperfusion injury (MI/RI). METHODS: MI/RI was induced in mice by ligation of the left anterior descending (LAD) artery followed by reperfusion, and the in vitro model was established in cultured cardiomyocytes under hypoxia/reoxygenation (H/R) conditions. Interaction among circ_0002612, miR-30a-5p, Ppargc1a, and NLRP3 was predicted by bioinformatics analysis and further experimentally identified. Gain- and loss-of-function experiments were performed to evaluate the effect of the circ_0002612/miR-30a-5p/Ppargc1a/NLRP3 axis on the cardiac function and myocardial infarction of I/R-injured mice, as well as viability and apoptosis of H/R-challenged cardiomyocytes. RESULTS: In the myocardial tissues of MI/RI mice, miR-30a-5p was negatively correlated with circ_0002612 or Ppargc1a, but circ_0002612 was positively correlated with the expression of Ppargc1a. circ_0002612 competitively bound to miR-30a-5p to release expression of its target gene Ppargc1a. circ_0002612 promoted cardiomyocyte viability while suppressing the apoptosis by impairing the miR-30a-5p-mediated inhibition of Ppargc1a. Additionally, Ppargc1a inhibited the expression of NLRP3 and consequently facilitated cardiomyocyte proliferation while suppressing cell apoptosis. By inhibiting the expression of NLRP3, circ_0002612 protected mice from MI/RI. CONCLUSION: Overall, this study demonstrates the cardioprotective role of circ_0002612 against MI/RI, which may be a viable target for MI/RI.
摘要：
Congenital syphilis, a significant cause of fetal mortality worldwide, is a congenital infectious disease instigated by the vertical transmission of Treponema pallidum during pregnancy. Clinical manifestations include preterm delivery, stillbirth, neonatal skin lesions, skeletal abnormalities, and central nervous system aberrations. The ongoing increase in the incidence of congenital syphilis, coupled with complexities in diagnosis, necessitates a detailed understanding of its pathogenesis for the development of improved diagnostic approaches, and to interrupt the route of vertical transmission. Drawing from the broader body of research associated with vertical transmission pathogens, we aim to clarify the potential mechanisms by which Treponema pallidum breaches the placental barrier to infect the fetus.
作者机构：
[Liu, Ying; Yang, Ke; He, Longwei; Wang, Peipei; Li, Songjiao] Univ South China, Hengyang Med Sch, Canc Res Inst, Hunan Prov Cooperat Innovat Ctr Mol Target New Dru, Hengyang 421001, Peoples R China.;[Cheng, Dan] Univ South China, Affiliated Nanhua Hosp, Hengyang Med Sch, Clin Res Inst, Hengyang, Peoples R China.
通讯机构：
[Dan Cheng] C;[Longwei He] H;Clinical Research Institute, The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang, China<&wdkj&>Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Cancer Research Institute, Department of Pharmacy and Pharmacology, Hengyang Medical School, University of South China, Hengyang, 421001, PR China
作者机构：
[Luo, Shihang] Univ South China, Affiliated Nanhua Hosp, Hengyang Med Sch, Dept Neurol, Hengyang, Hunan, Peoples R China.;[Chen, Hengshu; Mao, Rui; Mao, R] Cent South Univ, Xiangya Hosp, Changsha, Hunan, Peoples R China.;[Zhang, Tongtong] Southwest Jiaotong Univ, Peoples Hosp Chengdu 3, Affiliated Hosp, Med Res Ctr, Chengdu, Peoples R China.;[Zhang, Tongtong] Chongqing Med Univ, Affiliated Hosp Chengdu 2, Chengdu, Peoples R China.;[Zhang, Tongtong] Southwest Jiaotong Univ, Peoples Hosp Chengdu 3, Ctr Gastrointestinal & Minimally Invas Surg, Dept Gen Surg,Affiliated Hosp, Chengdu, Peoples R China.
通讯机构：
[Mao, R ] C;[Zhang, TT ] S;Cent South Univ, Xiangya Hosp, Changsha, Hunan, Peoples R China.;Southwest Jiaotong Univ, Peoples Hosp Chengdu 3, Affiliated Hosp, Med Res Ctr, Chengdu, Peoples R China.;Chongqing Med Univ, Affiliated Hosp Chengdu 2, Chengdu, Peoples R China.
关键词：
DNA methylation;Nomogram;Post-stroke depression
摘要：
OBJECTIVE: To construct a comprehensive nomogram model for predicting the risk of post-stroke depression (PSD) by using clinical data that are easily collected in the early stages, and the level of DNA methylation, so as to help doctors and patients prevent the occurrence of PSD as soon as possible. METHODS: We continuously recruited 226 patients with a history of acute ischemic stroke and followed up for three months. Socio-demographic indicators, vascular-risk factors, and clinical data were collected at admission, and the outcome of depression was evaluated at the third month after stroke. At the same time, a DNA-methylation-related sequencing test was performed on the fasting peripheral blood of the hospitalized patients which was taken the morning after admission. RESULTS: A total of 206 samples were randomly divided into training dataset and validation set according to the ratio of 7:3. We screened 24 potentially-predictive factors by Univariate logistic regression and least absolute shrinkage and selection operator (LASSO) regression analysis, and 10 of the factors were found to have predictive ability in the training set. The PSD nomogram model was established based on seven significant variables in multivariate logistic regression. The consistency statistic (C-index) was as high as 0.937, and the area under curve (AUC) in the ROC analysis was 0.933. Replication analysis results in the validation set suggest the C-index was 0.953 and AUC was 0.926. This shows that the model has excellent calibration and differentiating abilities. CONCLUSION: Gender, Rankin score, history of hyperlipidemia, time from onset to hospitalization, location of stroke, National Institutes of Health Stroke scale (NIHSS) score, and the methylation level of the cg02550950 site are all related to the occurrence of PSD. Using this information, we developed a prediction model based on methylation characteristics.
摘要：
ABCG1 is an essential protein involved in the efflux of intracellular cholesterol to the extracellular space, thus playing a critical role in reducing cholesterol accumulation in neighboring tissues. Bibliometric analysis pertains to the interdisciplinary field of quantitative examination of diverse documents using mathematical and statistical techniques. It integrates the investigation of structural and temporal patterns in academic publications with an exploration of subject focus and forms of uncertainty. This research paper examines the historical evolution, current areas of interest, and future development trends of ABCG1 through bibliometric analysis. This study aims to offer readers insights into the research status and emerging trends of ABCG1, thereby assisting researchers in the exciting field to explore novel research avenues. Following rigorous selection, research on ABCG1 has remained highly active over the past two decades. ABCG1 has even started to emerge in previously unrelated fields, such as the field of cancer research. According to the analysis conducted by Citespace, a lot of keywords and influential citations were identified. ABCG1 has been found to establish a connection between cancer and cardiovascular disease, highlighting their interrelationship. This review aims to assist readers who have limited familiarity with ABCG1 research in gaining a rapid understanding of its developmental trajectory. Additionally, it aims to offer researchers potential areas of focus for future studies related to ABCG1.
通讯机构：
[Chen, Z; Jiang, H ] C;Cent South Univ, Xiangya Hosp, Dept Neurol, Changsha 410008, Hunan, Peoples R China.;Cent South Univ, Dept Neurol, Xiangya Hosp 3, Changsha 410013, Hunan, Peoples R China.;Cent South Univ, Key Lab Hunan Prov Neurodegenerat Disorders, Changsha 410008, Hunan, Peoples R China.;Cent South Univ, Xiangya Hosp, Natl Clin Res Ctr Geriatr Disorders, Changsha 410008, Hunan, Peoples R China.
关键词：
Biomarker;Diagnosis;Multiple system atrophy;Parkinson’s disease;Plasma neurofilament light chain;Prediction
摘要：
BACKGROUND: The longitudinal dynamics of neurofilament light chain (NfL) in multiple system atrophy (MSA) were incompletely illuminated. This study aimed to explore whether the plasma NfL (pNfL) could serve as a potential biomarker of clinical diagnosis and disease progression for MSA. METHODS: We quantified pNfL concentrations in both a large cross-sectional cohort with 214 MSA individuals, 65 PD individuals, and 211 healthy controls (HC), and a longitudinal cohort of 84 MSA patients. Propensity score matching (PSM) was used to balance the age between the three groups. The pNfL levels between groups were comparedusing Kruskal-Wallis test. Linear mixed models were performed to explore the disease progression-associated factors in longitudinal MSA cohort. Random forest model as a complement to linear models was employed to quantify the importance of predictors. RESULTS: Before and after matching the age by PSM, the pNfL levels could reliably differentiate MSA from HC and PD groups, but only had mild potential to distinguish PD from HC. By combining linear and nonlinear models, we demonstrated that pNfL levels at baseline, rather than the change rate of pNfL, displayed potential prognostic value for progression of MSA. The combination of baseline pNfL levels and other modifiers, such as subtypes, Hoehn-Yahr stage at baseline, was first shown to improve the diagnosis accuracy. CONCLUSIONS: Our study contributed to a better understanding of longitudinal dynamics of pNfL in MSA, and validated the values of pNfL as a non-invasive sensitive biomarker for the diagnosis and progression. The combination of pNfL and other factors isrecommended for better monitoring and prediction of MSA progression.
期刊：
Molecular and Cellular Biochemistry,2023年478(4):755-765 ISSN：0300-8177
通讯作者：
Zhisheng Jiang
作者机构：
[Ren, Zhong; Jiang, Zhisheng; Zhang, Xiaofan] Univ South China, Hengyang Med Sch, Int Joint Lab Arteriosclerot Dis Res Hunan Prov, Inst Cardiovasc Dis,Key Lab Arteriosclerol Hunan, Hengyang 421001, Peoples R China.
通讯机构：
[Zhisheng Jiang] I;Institute of Cardiovascular Disease, Key Lab for Arteriosclerology of Hunan Province, International Joint Laboratory for Arteriosclerotic Disease Research of Hunan Province, Hengyang Medical School, University of South China, Hengyang, China
摘要：
Cardiovascular diseases, such as coronary artery disease and stroke, are the main threats to human health worldwide. Atherosclerosis, a chronic inflammatory disorder, plays a role as an initiator of all of the above-mentioned diseases. Cell therapy for diseases has attracted widespread attention. Mesenchymal stem cells (MSCs) are a type of stem cell that still exist in adults and have the characteristics of self-renewal ability, pluripotent differentiation potential, immunomodulation, tissue regeneration, anti-inflammation and low immunogenicity. In light of the properties of MSCs, some researchers have begun to target MSCs to create a possible way to alleviate atherosclerosis. Most of these studies are focused on MSC transplantation, injecting MSCs to modulate macrophages, the key inflammatory cell in atherosclerosis plaque. According to recent studies, researchers found that endothelial-to-mesenchymal transition (EndMT) has something to do with atherosclerosis development. A new cell typeMSC might also appear during the EndMT process. In this article, we summarize the characteristics of MSCs, the latest progress of MSC research and its application prospects, and in view of the process of EndMT occurring in atherosclerosis, we propose some new ideas for the treatment of atherosclerosis by targeting MSCs.
作者机构：
[Jiang, Weiwei] Southern Med Univ, Zhujiang Hosp, Dept Organ Transplantat, Guangzhou, Guangdong, Peoples R China.;[Long, Xiongquan] Hunan Normal Univ, Affiliated Hosp 1, Dept Gastroenterol, Changsha, Hunan, Peoples R China.;[Li, Zhicheng] Univ South China, Collage Pharm, Hengyang, Hunan, Peoples R China.;[Tang, Wanying; Ouyang, Yuxin; Ouyang, Xinping; Chen, Jinzhi; Zhang, Yangkai; Lin, Huiling; Hu, Mi] Univ South China, Inst Neurosci Res, Dept Physiol, Hengyang Key Lab Neurodegenerat & Cognit Impairmen, Hengyang, Hunan, Peoples R China.;[Jiang, Liping] Cent South Univ, Xiangya Hosp, Dept Clin Pharmacol, Changsha, Peoples R China.
通讯机构：
[Xinping Ouyang] T;The Research Center of Reproduction and Translational Medicine of Hunan Province, Department of Physiology, Medical College, Hunan Normal University, Changsha, China<&wdkj&>Department of Physiology, Institute of Neuroscience Research, Hengyang Key Laboratory of Neurodegeneration and Cognitive Impairment, University of South China, Hunan, China
摘要：
Ischemic stroke (IS), a devastating condition characterized by intracranial artery stenosis and middle cerebral artery occlusion leading to insufficient oxygen supply to the brain, is a major cause of death and physical disability worldwide. Recent research has demonstrated the critical role of circular RNAs (circRNAs), a class of covalently enclosed noncoding RNAs that are widespread in eukaryotic cells, in regulating various physiological and pathophysiological cellular processes, including cell apoptosis, autophagy, synaptic plasticity, and neuroinflammation. In the past few years, circRNAs have attracted extensive attention in the field of IS research. This review summarizes the current understanding of the mechanisms underlying the involvement of circRNAs in IS development. A better understanding of circRNA-mediated pathogenic mechanisms in IS may pave the way for translating circRNA research into clinical practice, ultimately improving the clinical outcomes of IS patients.
摘要：
Gonadotropin-releasing hormone (GnRH) is at the head of the neuroendocrine reproductive axis. However, the non-reproductive functions of GnRH expressed in various tissues, including hippocampus, are still not known. Here, we unveil a previously unknown effect of GnRH, which mediates depression-like behaviors through the modulation of microglia function during immune challenge. Specifically, we found that either systemic treatment with GnRH agonist or over-expression of endogenous hippocampal GnRH via viral tool abolished the depression-like behavior after LPS challenges in mice. And the anti-depressant of GnRH was dependent on the hippocampal GnRHR signaling, since antagonizing GnRHR by drug treatment or by hippocampal GnRHR knockdown could block the antidepressant-effect of GnRH agonist. Interestingly, we found that the peripheral GnRH treatment prevented the microglia activation mediated inflammation in the hippocampus of mice. In light of the research findings presented here, we propose that, at least in the hippocampus, GnRH appears to act on GnRHR to regulate higher order non-reproductive functions associated with the microglia mediated neuroinflammation. These findings also provide insights into the function and cross-talk of GnRH, a known neuropeptide hormone, in neuro-immune response.
