期刊：
International Immunopharmacology,2023年118:110035 ISSN：1567-5769
通讯作者：
Zhongyu Li
作者机构：
[Li, Zhongyu; Shi, Keliang; Shu, Mingyi; Zhao, Lanhua; Tang, Shuangyang] Univ South China, Inst Pathogen Biol, Hengyang Med Coll, Sch Nuring,Hunan Prov Key Lab Special Pathogens Pr, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Zhongyu Li] I;Institute of Pathogenic Biology, Hengyang Medical College, Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, the School of Nuring, University of South China, Hengyang, 421001 Hunan, PR China
摘要：
A core transcription regulatory circuitry (CRC) is an interconnected self-regulatory circuitry that is formed by a group of core transcription factors (TFs). These core TFs collectively regulate gene expression by binding not only to their own super enhancers (SEs) but also to the SEs of one another. For most human tissue/cell types, a global view of CRCs and core TFs has not been generated. Here, we identified numerous CRCs using two identification methods and detailed the landscape of the CRCs driven by SEs in large cell/tissue samples. The comprehensive biological analyses, including sequence conservation, CRC activity and genome binding affinity were conducted for common TFs, moderate TFs, and specific TFs, which exhibit different biological features. The local module located from the common CRC network highlighted the essential functions and prognostic performance. The tissue-specific CRC network was highly related to cell identity. Core TFs in tissue-specific CRC networks exhibited disease markers, andhad regulatory potential for cancer immunotherapy. Moreover, a user-friendly resource named CRCdb (http://www.licpathway.net/crcdb/index.html) was developed, which contained the detailed information of CRCs and core TFs used in this study, as well as other interesting results, such as the most representative CRC, frequency of TFs, and indegree/outdegree of TFs.
摘要：
The beneficial effects of gut flora on reducing nerve cell apoptosis and inflammation and improving epilepsy (EP) symptoms have been reported, but the specific mechanism of action is still unclear. A series of in vitro and in vivo experiments revealed the relationship between gut microbiota metabolites and the cGAS/STING axis and their role in EP. These results suggest that antibiotic-induced dysbiosisof gutmicrobiotaexacerbatedepilepticsymptoms, probiotic supplements reduced epileptic symptoms in mice. Antibiotics and probiotics altered the diversityandcompositionofgutmicrobiota. The changes in gut bacteria composition, such as in the abundance of Firmicutes, Bacteroidetes, Lactobacillus and Ruminococcus, were associated with the production of short-chain fatty acids (SCFA) in the gut. The concentrations of propionate, butyrate and isovalerate were changed after feeding antibiotics and probiotics, and the increase in butyrate levels reduced the expression of cGAS/STING in nerve cell further reduced Bax protein expression. The reduction of Bax protein attenuated the hippocampal neuron cell apoptosis in PTZ-induced EP and EP progression. Our findings provide new insights into the roles and mechanisms of action of the gut microbiota in attenuating EP symptoms and progression.
作者机构：
[Ye, Feng; Tang, Hailin] Sun Yat Sen Univ, State Key Lab Oncol South China, Canc Ctr, Guangzhou, Peoples R China.;[Dewanjee, Saikat] Jadavpur Univ, Dept Pharmaceut Technol, Adv Pharmacognosy Res Lab, Kolkata 700032, India.;[Li, Yuehua] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Med Oncol, Hengyang, Peoples R China.;[Li, Yuehua] Univ South China, Inst Pathogen Biol, Hengyang Med Coll, Hengyang, Peoples R China.;[Jha, Niraj Kumar; Jha, SK; Jha, Saurabh Kumar] Sharda Univ, Sch Engn & Technol, Dept Biotechnol, Greater Noida, India.
通讯机构：
[Tang, HL ; Jha, SK ] S;[Behl, T ] U;Sun Yat Sen Univ, State Key Lab Oncol South China, Canc Ctr, Guangzhou, Peoples R China.;Sharda Univ, Sch Engn & Technol, Dept Biotechnol, Greater Noida, India.;Univ Petr & Energy Studies, Sch Hlth Sci & Technol, Dehra Dun, Uttaranchal, India.
关键词：
Breast cancer;Clinical trials;Immune-checkpoint Inhibitors;Immunotherapy;Targeted therapies
摘要：
Breast cancer is the second leading cause of death for women worldwide. The heterogeneity of this disease presents a big challenge in its therapeutic management. However, recent advances in molecular biology and immunology enable to develop highly targeted therapies for many forms of breast cancer. The primary objective of targeted therapy is to inhibit a specific target/molecule that supports tumor progression. Ak strain transforming, cyclin-dependent kinases, poly (ADP-ribose) polymerase, and different growth factors have emerged as potential therapeutic targets for specific breast cancer subtypes. Many targeted drugs are currently undergoing clinical trials, and some have already received the FDA approval as monotherapy or in combination with other drugs for the treatment of different forms of breast cancer. However, the targeted drugs have yet to achieve therapeutic promise against triple-negative breast cancer (TNBC). In this aspect, immune therapy has come up as a promising therapeutic approach specifically for TNBC patients. Different immunotherapeutic modalities including immune-checkpoint blockade, vaccination, and adoptive cell transfer have been extensively studied in the clinical setting of breast cancer, especially in TNBC patients. The FDA has already approved some immune-checkpoint blockers in combination with chemotherapeutic drugs to treat TNBC and several trials are ongoing. This review provides an overview of clinical developments and recent advancements in targeted therapies and immunotherapies for breast cancer treatment. The successes, challenges, and prospects were critically discussed to portray their profound prospects.
摘要：
Syphilis, a sexually transmitted disease (STD) caused by Treponema pallidum (T. pallidum), has had a worldwide resurgence in recent years and remains a public health threat. As such, there has been a great deal of research into clinical strategies for the disease, including diagnostic biomarkers and possible strategies for treatment and prevention. Although serological testing remains the predominant laboratory diagnostic method for syphilis, it is worth noting that investigations pertaining to the DNA of T. pallidum, non-coding RNAs (ncRNAs), chemokines, and metabolites in peripheral blood, cerebrospinal fluid, and other bodily fluids have the potential to offer novel perspectives on the diagnosis of syphilis. In addition, the global spread of antibiotic resistance, such as macrolides and tetracyclines, has posed significant challenges for the treatment of syphilis. Fortunately, there is still no evidence of penicillin resistance. Hence, penicillin is the recommended course of treatment for syphilis, whereas doxycycline, tetracycline, ceftriaxone, and amoxicillin are viable alternative options. In recent years, efforts to discover a vaccine for syphilis have been reignited with better knowledge of the repertoire of T. pallidum outer membrane proteins (OMPs), which are the most probable syphilis vaccine candidates. However, research on therapeutic interventions and vaccine development for human subjects is limited due to practical and ethical considerations. Thus, the preclinical model is ideal for conducting research, and it plays an important role in clinical transformation. Different preclinical models have recently emerged, such as in vitro culture and mouse models, which will lay a solid foundation for clinical treatment and prevention of syphilis. This review aims to provide a comprehensive summary of the most recent syphilis tactics, including detection, drug resistance treatments, vaccine development, and preclinical models in clinical practice.
摘要：
Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disorder characterized by widespread intranuclear inclusions in the nervous system as well as multiple visceral organs. In 2019, expanded GGC repeats within the 5′ untranslated region of the NOTCH2NLC gene was identified as the causative factor. NIID is a heterogeneous disorder with variable clinical manifestations including cognitive impairment, cerebellar ataxia, parkinsonism, paroxysmal symptoms, autonomic dysfunction, and muscle weakness. Although NIID primarily affects the central and peripheral nervous systems, growing evidence suggests potential cardiac abnormalities in NIID. However, the link between expanded GGC repeats within NOTCH2NLC and cardiac dysfunction remains uncertain. In this study, we utilized two transgenic mouse models, expressing NOTCH2NLC-(GGC)98 ubiquitously or specifically in cardiomyocytes, and identified p62 (also known as sequestosome 1, SQSTM1)-positive intranuclear NOTCH2NLC-polyG inclusions in cardiomyocytes in two mouse models. We observed that both models exhibited cardiac-related pathological and echocardiographic changes, albeit exhibiting varying degrees of severity. Transcriptomic analysis revealed shared downregulation of genes related to ion channels and mitochondria in both models, with the cardiomyocyte-specific mice showing a more pronounced downregulation of mitochondria and energy metabolism-related pathways. Further investigations revealed decreased expression of mitochondria-related genes and electron transport chain activity. At last, we conducted a retrospective review of cardiac-related examination results from NIID patients at our hospital and also identified some cardiac abnormalities in NIID patients. Our study provided the first in vivo evidence linking GGC repeat expansions within NOTCH2NLC to cardiac abnormalities and highlighted the contribution of mitochondrial dysfunction in the development of cardiac abnormalities.
摘要：
Background The protective effects of astragaloside IV (ASIV) on various diseases are well known, but its potential impact on radiation-induced bystander effect (RIBE) has remained unclear. Objective This study aimed to explore the protective mechanism of ASIV against oxidative damage caused by RIBE in LO2 cells. Methods To construct the RIBE model, the conditioned medium from HepG2 cells irradiated with radiation was transferred to nonirradiated LO2 cells. LY294002, a commonly used phosphatidylinositol 3-kinase/Akt pathway inhibitor, was added to LO2 cells 1 h before exposing HepG2 cells to radiation. LO2 cells were then collected for analyses after RIBE exposure. Results The study found that ASIV significantly improved cell proliferation and promoted the recovery of mitochondrial membrane potential while reducing the rate of apoptosis. Western blot analyses demonstrated that ASIV upregulated B-cell lymphoma 2 and downregulated B-cell lymphoma 2-related X protein and cleaved-caspase 3. Measurement of reactive oxygen species, superoxide dismutase, glutathione peroxidase, and malondialdehyde levels showed that ASIV effectively restored the oxidative stress state induced by RIBE. Additionally, immunofluorescence and western blots analyses confirmed that ASIV enhanced the translocation of Nrf2 to the nucleus and activated downstream nicotinamide adenine dinucleotide phosphate: quinine oxidoreductase 1 and heme oxygenase 1. Importantly, Akt pathway inhibitor repressed ASIV-induced activation of Nrf2 and its protective effect against RIBE. Conclusion This study demonstrates that ASIV protects LO2 cells against oxidative damage caused by RIBE through activation of the Akt/Nrf2 pathway.
摘要：
Atherosclerosis (AS), a chronic vascular inflammatory disease, has become a main focus of attention worldwide for its chronic progressing disease course and serious complications in the later period. Nevertheless, explanations for the exact molecular mechanisms of AS initiation and development remain to be an unsolved problem. The classic pathogenesis theories, such as lipid percolation and deposition, endothelium injury, inflammation and immune damage, provide the foundation for discovering the new key molecules or signaling mechanisms. Recently, indoxyl sulfate (IS), one of non-free uremia toxins, has been noticeable for its multiple atherogenic effects. IS exists at high concentration in plasma for its great albumin binding rate. Patients with uremia have markedly elevated serum levels of IS due both to the deterioration of renal function and to the high binding affinity of IS to albumin. Nowadays, elevated incidence of circulatory disease among patients with renal dysfunction indicates correlation of uremic toxins with cardiovascular damage. In this review, the atherogenic effects of IS and the underlying mechanisms are summarized with emphasis on several key pathological events associated with AS developments, such as vascular endothelium dysfunction, arterial medial lesions, vascular oxidative stress, excessive inflammatory responses, calcification, thrombosis and foam cell formation. Although recent studies have proved the great correlation between IS and AS, deciphering cellular and pathophysiological signaling by confirming key factors involved in IS-mediated atherosclerosis development may enable identification of novel therapeutic targets.
摘要：
High altitude exposure leads to various cognitive impairments. The cerebral vasculature system plays an integral role in hypoxia-induced cognitive defects by reducing oxygen and nutrition supply to the brain. RNA N6-methyladenosine (m6A) is susceptible to modification and regulates gene expression in response to environmental changes, including hypoxia. However, the biological significance of m6A in endothelial cell performance under hypoxic conditions is unknown. Using m6A-seq, RNA immunoprcipitation-seq, and transcriptomic co-analysis, the molecular mechanism of vascular system remodeling under acute hypoxia is investigated. A novel m6A reader protein, proline-rich coiled-coil 2B (PRRC2B), exists in endothelial cells. PRRC2B knockdown promoted hypoxia-induced endothelial cell migration by regulating alternative splicing of the alpha 1 chain of collagen type XII in an m6A-dependent manner and the decay of matrix metallopeptidase domain 14 and ADAM metallopeptidase domain 19 mRNA in an m6A-independent manner. In addition, conditional knockout of PRRC2B in endothelial cells promotes hypoxia-induced vascular remodeling and cerebral blood flow redistribution, thus alleviating hypoxia-induced cognitive decline. Therefore, PRRC2B is integral in the hypoxia-induced vascular remodeling process as a novel RNA-binding protein. These findings provide a new potential therapeutic target for hypoxia-induced cognitive decline.
通讯机构：
[Huan He; Pingkun Zhou] D;Department of Radiation Toxicology and Oncology, Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, China<&wdkj&>NHC Key Laboratory of Radiobiology, School of Public Health, Jilin University, Changchun, China<&wdkj&>Department of Radiation Toxicology and Oncology, Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, China<&wdkj&>School of Medicine, University of South China, Hengyang, China
关键词：
TAB182;EGFR;Cell invasion;Cell migration;EMT;Lung cancer cells
摘要：
BACKGROUND: TAB182 is overexpressed in cancerous tissues and correlated with poor overall survival in lung cancer patients. Mechanistically, TAB182 participates in DNA damage repair and endows tumour cells with radio- and chemoresistance. However, its role in non-small cell lung cancer (NSCLC) remains unclear. METHODS AND RESULTS: Cells with stable TAB182 knockdown (KD) were generated using A549 NSCLC cells, and we demonstrated that depleting TAB182 inhibits cell EMT, proliferation, colony formation, migration and invasion. Analysis of the TCGA database showed a positive correlation between TAB182 and EGFR, a well-established NSCLC oncoprotein. Then, we verified that silencing TAB182 decreases EGFR expression at both the mRNA and protein levels. Moreover, both TAB182 and EGFR were reported to restore ionizing radiation (IR)-triggered DNA damage. We validated that IR elevates the protein level of EGFR and that silencing TAB182 can alleviate IR-induced EGFR upregulation. Furthermore, overexpressing EGFR abrogates the inhibitory effects of TAB182 KD on EMT, migration, and invasion in A549 cells. CONCLUSIONS: Our data demonstrated that EGFR expression is regulated by TAB182 and downregulation of TAB182 has a novel function to repress EMT, migration and invasion by decreasing EGFR, indicating TAB182 could regulate the malignant progression of NSCLC.
期刊：
JMIR PUBLIC HEALTH AND SURVEILLANCE,2023年9(1):e49291- ISSN：2369-2960
通讯作者：
Wang, J
作者机构：
[Wang, Jian; Guo, Qulian; Song, Zongbin; Hou, Xinran; Zhu, Maoen; Wang, J] Cent South Univ, Xiangya Hosp, Dept Anesthesiol, 87 Xiangya Rd, Changsha 410008, Peoples R China.;[Wang, Jian; Guo, Qulian; Song, Zongbin; Zhang, Chengliang; Hou, Xinran; Zhu, Maoen] Cent South Univ, Xiangya Hosp, Natl Clin Res Ctr Geriatr Disorders, Changsha, Peoples R China.;[Xu, Wei] Univ South China, Hunan Prov Maternal & Child Hlth Care Hosp, Dept Anesthesiol, Changsha, Peoples R China.;[Zhang, Chengliang] Cent South Univ, Xiangya Hosp, Dept Cardiovasc Surg, Changsha, Peoples R China.
通讯机构：
[Wang, J ] C;Cent South Univ, Xiangya Hosp, Dept Anesthesiol, 87 Xiangya Rd, Changsha 410008, Peoples R China.
关键词：
National Death Index;National Health and Nutrition Examination Survey;all-cause mortality;cause-specific mortality;serum chloride
摘要：
BACKGROUND: Chloride is the most abundant anion in the human extracellular fluid and plays a crucial role in maintaining homeostasis. Previous studies have demonstrated that hypochloremia can act as an independent risk factor for adverse outcomes in various clinical settings. However, the association of variances of serum chloride with long-term mortality risk in general populations has been rarely investigated. OBJECTIVE: This study aims to assess the association of serum chloride with all-cause and cause-specific mortality in the general American adult population. METHODS: Data were collected from 10 survey cycles (1999-2018) of the National Health and Nutrition Examination Survey. All-cause mortality, cardiovascular disease (CVD) mortality, cancer mortality, and respiratory disease mortality data were obtained by linkage to the National Death Index through December 31, 2019. After adjusting for demographic factors and relevant lifestyle, laboratory items, and comorbid factors, weighted Cox proportional risk models were constructed to estimate hazard ratios and 95% CIs for all-cause and cause-specific mortality. RESULTS: A total of 51,060 adult participants were included, and during a median follow-up of 111 months, 7582 deaths were documented, 2388 of CVD, 1639 of cancer, and 567 of respiratory disease. The weighted Kaplan-Meier survival analyses showed consistent highest mortality risk in individuals with the lowest quartiles of serum chloride. The multivariate-adjusted hazard ratios from lowest to highest quartiles of serum chloride (≤101.2, 101.3-103.2, 103.2-105.0, and ≥105.1 mmol/L) were 1.00 (95% CI reference), 0.77 (95% CI 0.67-0.89), 0.72 (95% CI 0.63-0.82), and 0.77 (95% CI 0.65-0.90), respectively, for all-cause mortality (P for linear trend<.001); 1.00 (95% CI reference), 0.63 (95% CI 0.51-0.79), 0.56 (95% CI 0.43-0.73), and 0.67 (95% CI 0.50-0.89) for CVD mortality (P for linear trend=.004); 1.00 (95% CI reference), 0.67 (95% CI 0.54-0.84), 0.65 (95% CI 0.50-0.85), and 0.65 (95% CI 0.48-0.87) for cancer mortality (P for linear trend=.004); and 1.00 (95% CI reference), 0.68 (95% CI 0.41-1.13), 0.59 (95% CI 0.40-0.88), and 0.51 (95% CI 0.31-0.84) for respiratory disease mortality (P for linear trend=.004). The restricted cubic spline analyses revealed the nonlinear and L-shaped associations of serum chloride with all-cause and cause-specific mortality (all P for nonlinearity<.05), in which lower serum chloride was prominently associated with higher mortality risk. The associations of serum chloride with mortality risk were robust, and no significant additional interaction effect was detected for all-cause mortality and CVD mortality (P for interaction>.05). CONCLUSIONS: In American adults, decreased serum chloride concentrations were independently associated with increased all-cause mortality, CVD mortality, cancer mortality, and respiratory disease mortality. Our findings suggested that serum chloride may serve as a promising cost-effective health indicator in the general adult population. Further studies are warranted to explore the potential pathophysiological mechanisms underlying the association between serum chloride and mortality.
作者机构：
[Liao, Yating; Zeng, Zhuo; Ye, Youyuan; Peng, Kailan; Zeng, Yanhua; Li, Xia; Chen, Li] Univ South China, Inst Pathogen Biol, Hengyang Med Coll, Basic Med Sch,Hunan Prov Key Lab Special Pathogens, Hengyang, Hunan, Peoples R China.;[Zeng, Dongdong] Univ South China, Affiliated Hosp 3, Dept Cardiocascular Med, Hengyang, Hunan, Peoples R China.
通讯机构：
[Yanhua Zeng] I;Institute of Pathogenic Biology, Basic Medical School, Hengyang Medical College, Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, University of South China, Hengyang, Hunan Province, People’s Republic of China
摘要：
Mycoplasma pneumoniae is the most common pathogen causing respiratory tract infection, and the P1 protein on its adhesion organelle plays a crucial role during the pathogenic process. A variety of experiments, including enzyme-linked immunosorbent assay (ELISA), coimmunoprecipitation, adhesion, and adhesion inhibition assay, have demonstrated that the M. pneumoniae P1 protein can interact with vimentin, that the adhesion of M. pneumoniae and recombinant P1 protein to BEAS-2B cells was affected by the expression level of vimentin. Mycoplasma pneumoniae is the most common pathogen causing respiratory tract infection, and the P1 protein on its adhesion organelle plays a crucial role during the pathogenic process. Currently, there are many studies on P1 and receptors on host cells, but the adhesion mechanism of P1 protein is still unclear. In this study, a modified virus overlay protein binding assay (VOPBA) and liquid chromatography-mass spectrometry (LC-MS) were performed to screen for proteins that specifically bind to the region near the carboxyl terminus of the recombinant P1 protein (rP1-C). The interaction between rP1-C and vimentin or beta-4-tubulin were confirmed by far-Western blotting and coimmunoprecipitation. Results verified that vimentin and beta-4-tubulin were mainly distributed on the cell membrane and cytoplasm of human bronchial epithelial (BEAS-2B) cells, but only vimentin could interact with rP1-C. The results of the adhesion and adhesion inhibition assays indicated that the adhesion of M. pneumoniae and rP1-C to cells could be partly inhibited by vimentin and its antibody. When vimentin was downregulated with the corresponding small interfering RNA (siRNA) or overexpressed in BEAS-2B cells, the adhesion of M. pneumoniae and rP1-C to cells was decreased or increased, respectively, which indicated that vimentin was closely associated with the adhesion of M. pneumoniae and rP1-C to BEAS-2B cells. Our results demonstrate that vimentin could be a receptor on human bronchial epithelial cells for the P1 protein and plays an essential role in the adhesion of M. pneumoniae to cells, which may clarify the pathogenesis of M. pneumoniae.IMPORTANCE Mycoplasma pneumoniae is the most common pathogen causing respiratory tract infection, and the P1 protein on its adhesion organelle plays a crucial role during the pathogenic process. A variety of experiments, including enzyme-linked immunosorbent assay (ELISA), coimmunoprecipitation, adhesion, and adhesion inhibition assay, have demonstrated that the M. pneumoniae P1 protein can interact with vimentin, that the adhesion of M. pneumoniae and recombinant P1 protein to BEAS-2B cells was affected by the expression level of vimentin. This provides a new idea for the prevention and treatment of Mycoplasma pneumoniae infection.
摘要：
Located in the frontline against the largest population of microbiota, the intestinal mucosa of mammals has evolved to become an effective immune system. ?d T cells, a unique T cell subpopulation, are rare in circulation blood and lymphoid tissues, but rich in the intestinal mucosa, particularly in the epithelium. Via rapid production of cytokines and growth factors, intestinal ?d T cells are key contributors to epithelial homeostasis and immune surveillance of infection. Intriguingly, recent studies have revealed that the intestinal ?d T cells may play novel exciting functions ranging from epithelial plasticity and remodeling in response to carbohydrate diets to the recovery of ischemic stroke. In this review article, we update regulatory molecules newly defined in lymphopoiesis of the intestinal ?d T cells and their novel functions locally in the intestinal mucosa, such as epithelial remodeling, and distantly in pathological setting, e.g., ischemic brain injury repair, psychosocial stress responses, and fracture repair. The challenges and potential revenues in intestinal ?d T cell studies are discussed.
通讯机构：
[Tang, CK ] U;Univ South China, Inst Cardiovasc Res, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Key Lab Atherosclerol Hunan Prov, Hengyang, Hunan, Peoples R China.
关键词：
Atherosclerosis;PTPN2;inflammatory response;inflammatory cytokines Abbreviations: PTPN2;Tyrosine-protein phosphatase non-receptor type 2;CVD;Cardiovascular disease;As;Atherosclerosis;VECs;vascular endothelial cells;TCPTP;T-cell protein-tyrosine phosphatase;MAPK;Mitogen-Activated Protein
摘要：
Tyrosine-protein phosphatase non-receptor type 2(PTPN2), an important member of the protein tyrosine phosphatase family, can regulate various signaling pathways and biological processes by dephosphorylating receptor protein tyrosine kinases. Accumulating evidence has demonstrated that PTPN2 is involved in the occurrence and development of atherosclerotic cardiovascular disease. Recently, it has been reported that PTPN2 exerts an anti-atherosclerotic effect by regulating vascular endothelial injury, monocyte proliferation and migration, macrophage polarization, T cell polarization, autophagy, pyroptosis, and insulin resistance. In this review, we summarize the latest findings on the role of PTPN2 in the pathogenesis of atherosclerosis to provide a rationale for better future research and therapeutic interventions.
作者机构：
[Wang, Yang; Tang, Chao-Ke; Li, Heng] Univ South China, Inst Cardiovasc Dis, Hunan Prov Cooperat Innovat Ctr Mol Target New Dru, Hengyang Med Sch,Key Lab Arteriosclerol Hunan Prov, Hengyang 421001, Hunan, Peoples R China.;[Yu, Xiao-Hua] Hainan Med Univ, Affiliated Hosp 2, Inst Clin Med, Haikou 460106, Hainan, Peoples R China.
通讯机构：
[Chao-Ke Tang] I;Institute of Cardiovascular Disease, Key Laboratory for Arteriosclerology of Hunan Province, Hunan International Scientific and Technological Cooperation Base of Arteriosclerotic disease, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China
摘要：
Cardiovascular diseases (CVDs) are a series of diseases induced by inflammation and lipid metabolism disorders, among others. Metabolic diseases can cause inflammation and abnormal lipid metabolism. C1q/TNF-related proteins 1 (CTRP1) is a paralog of adiponectin that belongs to the CTRP subfamily. CTRP1 is expressed and secreted in adipocytes, macrophages, cardiomyocytes, and other cells. It promotes lipid and glucose metabolism but has bidirectional effects on the regulation of inflammation. Inflammation can also inversely stimulate CTRP1 production. A vicious circle may exist between the two. This article introduces CTRP1 from the structure, expression, and different roles of CTRP1 in CVDs and metabolic diseases, to summarize the role of CTRP1 pleiotropy. Moreover, the proteins which may interact with CTRP1 are predicted through GeneCards and STRING, speculating their effects, to provide new ideas for the study of CTRP1.
摘要：
This study was designed to investigate paclitaxel's total efficiency and safety combined with cisplatin in treating advanced esophageal cancer patients. Eighty-eight patients with advanced esophageal cancer were were divided into two groups with different treatment regimens: the control group was treated with 5-fluorouracil combined with cisplatin while the study group was treated with paclitaxel combined with cisplatin. The observed indexes include, the time of tumor progression and median survival between the two groups, the changes in pain score, vertical tumor diameter, and tumor diameter before and after treatment, the total efficiency of treatment as well as the safety of the two groups. Compared with the control group, the time to tumor progression and median survival were longer in the study group (p < 0.05). The total efficien-cy of treatment was higher in the study group (p < 0.05) as compared to control group similarly compared to the control group, all adverse effects were less severe in the study group. The use of paclitaxel combined with cisplatin in the treatment of advanced esophageal cancer patients can further prolong the survival time of patients compared with 5-fluorouracil combined with cisplatin, with higher total clinical efficiency, fewer adverse reactions, and certain safety, which is worthy of clinical promotion.
作者机构：
[Wang, Yan Xia; Tian, Zhen; Zheng, Hong Yu; Liu, Hui Ting; Deng, Nian Hua; Wu, Ze Fan; Liu, Xi Yan; Jiang, Zhi Sheng] Univ South China, Inst Cardiovasc Dis, Hengyang Med Coll, Key Lab Arteriosclerosis Hunan Prov, Hengyang, Hunan, Peoples R China.;[Zhou, Zhan Yang] Chinese Acad Med Sci & Peking Union Med Coll, Fu Wai Hosp, Dept Cardiol, Beijing, Peoples R China.;[Ou, Yang Shao] Univ South China, Hosp 2, Hengyang, Hunan, Peoples R China.;[Jiang, Zhi Sheng] Univ South China, Inst Cardiovasc Dis, Hengyang Med Coll, Key Lab Arteriosclerosis Hunan Prov, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Zhi Sheng Jiang PhD; Zhi Sheng Jiang PhD Zhi Sheng Jiang PhD Zhi Sheng Jiang PhD] I;Institute of Cardiovascular Disease, Key Laboratory for Arteriosclerosis of Hunan Province, Hengyang Medical College, University of South China, Hengyang, Hunan, PR China
摘要：
Statins have been proven to be effective in minimizing the risk of cardiovascular adverse events, however, their effect on BP variability is debatable with respect to their significance and their use as a potential anti-hypertensive. Using a meta-analysis approach, the aim of this study was to explore whether certain statins have the potential to lower blood pressure (BP). For the period 2002-2022, Scopus, PubMed, Web of Science, and the Cochrane Central Register of Controlled Trials databases were searched for the studies that examined the effect of statins on blood pressure in normotensive or hypertensive individuals. Randomized controlled clinical trials that investigated this effect were included based on our inclusion criteria. Our primary outcomes were changes in systolic and diastolic blood pressure (DBP). The final analysis of the study included 49 RCTs involving 45 173 participants randomized to receive either statins or placebo. Among the two groups, the total weighted mean difference (WMD) for systolic blood pressure (Delta SBP) was -1.42 (95% CI: -2.38, -0.46; p = .004) and diastolic blood pressure (Delta DBP) was 0.82 (95% CI: -1.28, -0.36; p = .0005). Despite various studies suggesting the efficacy of statins in blood pressure lowering to be significant and non-significant both, we observed a decrease in SBP and DBP both, although the change was not as large and could be considered significant. A large multicenter, multi-ethnic, large sample pool size, and a long period follow-up study is still required to assert these claims.
期刊：
PATHOLOGY RESEARCH AND PRACTICE,2023年248:154634 ISSN：0344-0338
通讯作者：
Cao, JY;Dai, T
作者机构：
[Cao, Jingying] Cent South Univ, Xiangya Hosp 3, Dept Med Clin Lab, Changsha 410013, Hunan, Peoples R China.;[Cao, Renxian] Univ South China, Affiliated Hosp 1, Inst Clin Med, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.;[Liu, Yiqi] Univ South China, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.;[Dai, Tao] Cent South Univ, Xiangya Sch Med, Hunan Canc Hosp, Affiliated Canc Hosp,Dept Urol, Changsha 410013, Hunan, Peoples R China.;[Cao, Jingying; Cao, JY] Cent South Univ, Xiangya Hosp 3, Dept Med Clin Lab, 138 Tongzipo Rd, Changsha 410013, Hunan, Peoples R China.
通讯机构：
[Dai, T ; Cao, JY ] C;Cent South Univ, Xiangya Hosp 3, Dept Med Clin Lab, 138 Tongzipo Rd, Changsha 410013, Hunan, Peoples R China.;Cent South Univ, Xiangya Sch Med, Hunan Canc Hosp, Affiliated Canc Hosp,Dept Urol, 283 Tongzipo Rd, Changsha 410013, Hunan, Peoples R China.
关键词：
AKT;CPNE1;Glycolysis;PI3K;Triple-negative breast cancer
摘要：
CPNE1 regulates multiple signaling pathways and can stimulate cell proliferation and differentiation by activating the AKT-mTOR signaling pathway. In addition, CPNE1 is associated with various cancers; however, its role in breast cancer, particularly in TNBC, has not been fully elucidated. Our study aimed to reveal the impact of the CPNE1/PI3K/AKT/HIF-1α axis on TNBC. We first measured the expression of CPNE1 in the tumor tissues of TNBC patients and examined its prognostic value. Subsequently, we used sh-CPNE1 and overexpression vectors to transfect TNBC cell lines and analyzed cell viability, migration, and invasive abilities using colony formation and CCK-8 assays. Metabolites were analyzed through metabolomics. We found that higher expression of CPNE1 predicted poor prognosis in TNBC patients. Knockdown of CPNE1 reduced the viability, migration, invasion, and proliferation capabilities of TNBC cells. Furthermore, metabolomics analysis showed that glucose metabolism was the most dominant pathway, and knockdown of CPNE1 significantly limited the glycolytic activity of TNBC cells. We verified these conclusions in mouse models. Additionally, we overexpressed CPNE1 and treated TNBC cell lines with a PI3K inhibitor (LY294002). The results indicated that CPNE1 promoted aerobic glycolysis in TNBC cells through the PI3K/AKT/HIF-1α signaling pathway. This suggests that CPNE1 regulates cell glycolysis and participates in the development of TNBC. Our study may provide a new therapeutic target for TNBC treatment.
