作者机构：
[Shen, Hongrong; Wang, Jinling; Gao, Hui; Li, Ping; Zhou, Shuwei; Li, Jianyu; Zhong, Zeya; You, Tian; Hu, Xiaoli; Luo, Muqing; Yan, Luyou; Zhang, Kun; He, Yewen] Hunan Univ Chinese Med, Hosp 1, Dept Radiol, 95 Shaoshan Middle Rd, Changsha 410007, Peoples R China.;[Wang, Jinling; Zhou, Shuwei; Zhang, Kun] Hunan Univ Chinese Med, Coll Integrated Tradit Chinese & Western Med, 300 Xueshi Rd, Changsha 410208, Peoples R China.;[Chen, Suping] GE Healthcare Shanghai Co Ltd, Shanghai 201203, Peoples R China.
通讯机构：
[Kun Zhang] D;Department of Radiology, The First Hospital of Hunan University of Chinese Medicine, Changsha, People’s Republic of China<&wdkj&>College of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, People’s Republic of China
摘要：
With the aging population of society, the incidence rate of osteoporosis is increasing year by year. Early diagnosis of osteoporosis plays a significant role in the progress of disease prevention. As newly developed technology, computed tomography (CT) radiomics could discover radiomic features difficult to recognize visually, providing convenient, comprehensive and accurate osteoporosis diagnosis. This study aimed to develop and validate a clinical-radiomics model based on the monochromatic imaging of single source dual-energy CT for osteoporosis prediction. One hundred sixty-four participants who underwent both single source dual-energy CT and quantitative computed tomography (QCT) lumbar-spine examination were enrolled in a study cohort including training datasets (n = 114 [30 osteoporosis and 84 non-osteoporosis]) and validation datasets (n = 50 [12 osteoporosis and 38 non-osteoporosis]). One hundred seven radiomics features were extracted from 70-keV monochromatic CT images. With QCT as the reference standard, a radiomics signature was built by using least absolute shrinkage and selection operator (LASSO) regression on the basis of reproducible features. A clinical-radiomics model was constructed by incorporating the radiomics signature and a significant clinical predictor (age) using multivariate logistic regression analysis. Model performance was assessed by its calibration, discrimination and clinical usefulness. The radiomics signature comprised 14 selected features and showed good calibration and discrimination in both training and validation cohorts. The clinical-radiomics model, which incorporated the radiomics signature and a significant clinical predictor (age), also showed good discrimination, with an area under the receiver operating characteristic curve (AUC) of 0.938 (95% confidence interval, 0.903–0.952) in the training cohort and an AUC of 0.988 (95% confidence interval, 0.967–0.998) in the validation cohort, and good calibration. The clinical-radiomics model stratified participants into groups with osteoporosis and non-osteoporosis with an accuracy of 94.0% in the validation cohort. Decision curve analysis (DCA) demonstrated that the radiomics signature and the clinical-radiomics model were clinically useful. The clinical-radiomics model incorporating the radiomics signature and a clinical parameter had a good ability to predict osteoporosis based on dual-energy CT monoenergetic imaging.
作者机构：
[Xiao, Yanni] Hunan Univ Chinese Med, Coll Integrated Tradit Chinese & Western Med, Changsha, Hunan, Peoples R China.;[Xiao, Yanni; Tang, Chuwen; Luo, Zhihong; Xiao, Pengfei; Zeng, Xianxiang] Brain Hosp Hunan Prov, Changsha, Hunan, Peoples R China.;[Yu, Yu] Yale Sch Med, Dept Psychiat, Div Prevent & Community Res, New Haven, CT USA.;[Tang, Chuwen; Zhou, Ziqi] Hunan Univ Chinese Med, Grad Sch, Changsha, Hunan, Peoples R China.;[Zhou, Ziqi] Hunan Univ Chinese Med, Hosp 1, Dept Obstet & Gynecol, Changsha, Hunan, Peoples R China.
通讯机构：
[Shen, MX ; Luo, ZH; Zeng, XX] C;Cent South Univ, Xiangya Sch Publ Hlth, Dept Social Med & Hlth Management, Changsha, Hunan, Peoples R China.;Furong Lab, Changsha, Hunan, Peoples R China.
关键词：
Mental disorder;Schizophrenia;Hospitalization;Spending;Length of hospital stay
摘要：
Objectives: To describe hospital spending and length of stay for mental disorders in Hunan, China.Methods: We extracted hospital care data for Hunan province from the Chinese National Health Statistics Network Reporting System. Patients with mental disorders (ICD-10 codes: F00 to F99) as the principal diagnosis and hospitalized between January 1, 2017 and December 31, 2019 were included. We retrieved information on age, sex, number of comorbidities, diagnosis, level of hospital, hospital costs, date of admission and discharge, length of stay (LOS), and method of payment of eligible participants. Spending at the provincial level, and spending and LOS at the individual level were described. Quantile regression and linear regression were conducted to investigate factors for hospital cost and LOS for major mental disorders.Results: The 2019 annual spending on mental disorders in Hunan province was 160 million US dollars, and 71.7% was paid by insurance. The annual spending on schizophrenia was 84 million dollars, contributing to a primary burden of mental disorders. The median spending for mental disorders was $1,085 per patient, and the median hospital stay was 22 days. The study identified several significant factors associated with hospital cost and LOS, including age, sex, comorbidity, and level of the hospital. In particular, a higher level of the hospital was associated with a higher hospital spending but a shorter LOS. Women with schizophrenia had a comparable hospital spending but a significantly shorter LOS than men with schizophrenia.Conclusion: Hospitalization spending for patients with mental disorders is substantial. Schizo- phrenia is the major burden of hospitalization for mental disorders. While patients treated at a higher level of hospital had higher spending, they stayed shorter in these hospitals.
期刊：
Naunyn-Schmiedeberg's Archives of Pharmacology,2023年396(5):831-849 ISSN：0028-1298
通讯作者：
Zhigang Mei
作者机构：
[Chen, Xiangyu; Yang, Tong; Ge, Jinwen; Fang, Rui; Mei, Zhigang] Hunan Univ Chinese Med, Coll Integrated Tradit Chinese & Western Med, Key Lab Hunan Prov Integrated Tradit Chinese & Wes, Changsha 410208, Hunan, Peoples R China.;[Feng, Zhitao; Luo, Yanan] China Three Gorges Univ, Third Grade Pharmacol Lab Chinese Med, State Adm Tradit Chinese Med, Med Coll, Yichang 443002, Hubei, Peoples R China.
通讯机构：
[Zhigang Mei] T;The Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine On Prevention and Treatment of Cardio-Cerebral Diseases, College of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, China
关键词：
ARRIVE;Buyang Huanwu decoction;Cerebral ischemia–reperfusion injury;Methodological and reporting quality;SYRCLE
摘要：
Buyang Huanwu decoction, a classic traditional Chinese prescription, has been used to prevent and treat stroke for hundreds of years. An increasing number of the laboratory research on Buyang Huanwu decoction used in treating cerebral ischemia-reperfusion injury have been published recently. However, the problem of methodological and reporting quality of some studies is lack of assessment. This study aims to evaluate the methodological and reporting quality of the research on Buyang Huanwu decoction against experimental cerebral ischemia-reperfusion injury. A comprehensive search on six databases was performed. Two researchers independently screened the literature considering the eligibility criteria. Methodological and reporting quality of the included studies were evaluated by the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) risk-of-bias tool and Animal Research: Reporting of In Vivo Experiments (ARRIVE) guideline. Forty-five studies met the inclusion criteria. No study achieved a decent overall rating in using the SYRCLE tool (percentage of items with "low risk" ≥ 50%). Of the 22 items on the SYRCLE tool, only 7 items (31.82%) were rated as "low risk" in more than 50% of the included studies. Of the 39 items of ARRIVE guideline, 14 (35.9%) items were rated as "yes" in more than 50% of the included studies. The methodological and reporting quality of Buyang Huanwu decoction for experimental cerebral ischemia-reperfusion injury was substandard, which needed to be further improved. The limitations should be addressed when planning similar studies in the future. Additionally, these findings provided evidence-based guidance for future preclinical studies evaluating the efficacy of Buyang Huanwu decoction in the treatment of cerebral ischemia-reperfusion injury.
摘要：
The stress response molecule nuclear protein‑1 (NUPR1) is essential for the growth of multiple types of human malignant tumor cells. However, the significance of NUPR1 in lung cancer is still not entirely elucidated. Therefore, this study is aimed to explore the function and underlying mechanisms of NUPR1 in lung cancer. NUPR1 mRNA and protein levels in lung cancer cell lines (A549 or H1299 cells) were silenced through siRNA transfection and western blot observed its successful infection efficiency. Then, using tube formation and wound healing experiments, the effects of si-NUPR1 on angiogenesis and migration of human umbilical vein endothelial cells (HUVEC) were examined, respectively, which indicated inhibitory effects on the angiogenesis and migration of HUVEC. Vascular endothelial growth factor A (VEGFA), a vital molecule in angiogenesis, was detected by PCR and western blot assays, manifesting NUPR1 knockdown represses VEGFA expression. Furthermore, the knockdown of NUPR1 may reduce angiogenesis by lowering VEGFA expression through inositol-requiring enzyme 1 (IRE1)/X box binding protein 1 (XBP1) and protein kinase RNA-like endoplasmic reticulum kinase (PERK)/eukaryotic translation initiation factor 2 A (eIF2α)/recombinant activating transcription factor 4 (ATF4) signaling pathways in A549 or H1299 cells. In conclusion, these findings demonstrated that NUPR1 knockdown inhibits angiogenesis in A549 and H1299 cells through IRE1/XBP1 and PERK/eIF2α/ATF4 signaling pathways, indicating that NUPR1 could represent a novel lung cancer therapeutic target.
摘要：
To examine the effects of clomiphene citrate (CC) on follicular fluid metabolites and related metabolic pathways in rats with polycystic ovary syndrome (PCOS) using non-targeted metabolomics and determine how CC treats ovulation disorder in PCOS. The Sprague Dawley rats were randomly divided into control, model, and CC groups. A PCOS model was established with letrozole. Body weight, ovarian weight, estrus cycles, serum hormone levels, and ovary histopathology of the rats were collected for further evaluation. Moreover, through ultra-performance liquid chromatography-mass spectrometry, the study of follicular fluid metabolites revealed the mechanism of action of CC. CC reduced ovarian weight and regulated estrous cycles and serum hormone levels in PCOS rats but did not affect their body weight. Moreover, the metabolomic results showed that CC adjusted 153 metabolites, among which 16 cross metabolites like testosterone, androstenedione, 17α-hydroxyprogesterone, and cholic acid were considered as potential biomarkers for CC to improve ovulation disorders in PCOS rats. Kyoto Encyclopedia of Genes and Genomes pathway enrichment also showed that the CC group mainly engaged in tryptophan metabolism and steroid hormone biosynthesis. CC can improve ovulation disorders in rats, and its mechanism is related to the regulation of the secretion of serum hormone and follicular fluid metabolites and the amelioration of multi-metabolic pathways.
关键词：
atherosclerosis;endothelial cell;endothelial cell senescence;endothelial cell death
摘要：
Endothelial cells (ECs) form the inner linings of blood vessels, and are directly exposed to endogenous hazard signals and metabolites in the circulatory system. The senescence and death of ECs are not only adverse outcomes, but also causal contributors to endothelial dysfunction, an early risk marker of atherosclerosis. The pathophysiological process of EC senescence involves both structural and functional changes and has been linked to various factors, including oxidative stress, dysregulated cell cycle, hyperuricemia, vascular inflammation, and aberrant metabolite sensing and signaling. Multiple forms of EC death have been documented in atherosclerosis, including autophagic cell death, apoptosis, pyroptosis, NETosis, necroptosis, and ferroptosis. Despite this, the molecular mechanisms underlying EC senescence or death in atherogenesis are not fully understood. To provide a comprehensive update on the subject, this review examines the historic and latest findings on the molecular mechanisms and functional alterations associated with EC senescence and death in different stages of atherosclerosis.
作者机构：
[Wang, Yang; Su, Hong; Yan, Qiuju; Hu, En; Tang, Tao; Li, Teng; Li, Zhilin] Cent South Univ, Xiangya Hosp, Inst Integrat Med, Dept Integrated Tradit Chinese & Western Med, Changsha, Peoples R China.;[Su, Hong; Yan, Qiuju; Hu, En; Tang, Tao; Li, Teng; Li, Zhilin] Cent South Univ, Xiangya Hosp, Natl Clin Res Ctr Geriatr Disorders, Changsha, Peoples R China.;[Wang, Lei] Xiangxiang Peoples Hosp, Dept Resp Dis, Xiangxiang, Peoples R China.;[Li, Haigang] Changsha Med Univ, Hunan Key Lab Res & Dev Novel Pharmaceut Preparat, Changsha, Peoples R China.;[Zhang, Wei] Hunan Univ Chinese Med, Coll Integrated Tradit Chinese & Western Med, Changsha, Peoples R China.
通讯机构：
[Tang, T; Wang, Y ] C;Cent South Univ, Xiangya Hosp, Inst Integrat Med, Dept Integrated Tradit Chinese & Western Med, Changsha 410008, Hunan, Peoples R China.
关键词：
Network pharmacology;brain-derived neurotrophic factor;signal transducer and activator of transcription 3;growth-associated protein 43;cortex;hippocampus;traditional Chinese medicine
摘要：
Context Hydroxysafflor yellow A (HSYA) is the main bioactive ingredient of safflower (Carthamus tinctorius L., [Asteraceae]) for traumatic brain injury (TBI) treatment. Objective To explore the therapeutic effects and underlying mechanisms of HSYA on post-TBI neurogenesis and axon regeneration. Materials and methods Male Sprague-Dawley rats were randomly assigned into Sham, controlled cortex impact (CCI), and HSYA groups. Firstly, the modified Neurologic Severity Score (mNSS), foot fault test, hematoxylin-eosin staining, Nissl's staining, and immunofluorescence of Tau1 and doublecortin (DCX) were used to evaluate the effects of HSYA on TBI at the 14th day. Next, the effectors of HSYA on post-TBI neurogenesis and axon regeneration were screened out by pathology-specialized network pharmacology and untargeted metabolomics. Then, the core effectors were validated by immunofluorescence. Results HSYA alleviated mNSS, foot fault rate, inflammatory cell infiltration, and Nissl's body loss. Moreover, HSYA increased not only hippocampal DCX but also cortical Tau1 and DCX following TBI. Metabolomics demonstrated that HSYA significantly regulated hippocampal and cortical metabolites enriched in 'arginine metabolism' and 'phenylalanine, tyrosine and tryptophan metabolism' including l-phenylalanine, ornithine, l-(+)-citrulline and argininosuccinic acid. Network pharmacology suggested that neurotrophic factor (BDNF) and signal transducer and activator of transcription 3 (STAT3) were the core nodes in the HSYA-TBI-neurogenesis and axon regeneration network. In addition, BDNF and growth-associated protein 43 (GAP43) were significantly elevated following HSYA treatment in the cortex and hippocampus. Discussion and conclusions HSYA may promote TBI recovery by facilitating neurogenesis and axon regeneration through regulating cortical and hippocampal metabolism, BDNF and STAT3/GAP43 axis.
期刊：
Frontiers in Microbiology,2023年14:1182006 ISSN：1664-302X
通讯作者：
Zhang, SF
作者机构：
[Ou, Qinling; Zhang, SF; Zhang, Sifang; Chang, Yonglong] Cent South Univ, Xiangya Hosp 2, Dept Integrated Tradit Chinese & Western Med, Changsha, Peoples R China.;[Ou, Qinling; Zhang, SF; Zhang, Sifang] Natl Clin Res Ctr Metab Dis, Changsha, Peoples R China.;[Zhou, Xuhui] Brain Hosp Hunan Prov, Peoples Hosp Hunan Prov 2, Hunan Inst Mental Hlth, Dept Addict Med, Changsha, Peoples R China.;[Liu, Jinhui] Hunan Univ Tradit Chinese Med, Coll Integrated Tradit Chinese & Western Med, Changsha, Peoples R China.
通讯机构：
[Zhang, SF ] C;Cent South Univ, Xiangya Hosp 2, Dept Integrated Tradit Chinese & Western Med, Changsha, Peoples R China.;Natl Clin Res Ctr Metab Dis, Changsha, Peoples R China.
作者机构：
[She, Ruining; Ge, Jinwen; Mei, Zhigang] Hunan Univ Chinese Med, Coll Integrated Tradit Chinese & Western Med, Key Lab Hunan Prov Integrated Tradit Chinese & Wes, Changsha, Hunan, Peoples R China.;[Ge, Jinwen] Hunan Acad Tradit Chinese Med, Changsha, Hunan, Peoples R China.;[Mei, Zhigang] China Three Gorges Univ, Grade Pharmacol Lab Chinese Med Approved 3, State Adm Tradit Chinese Med, Coll Med & Hlth Sci, Yichang 443002, Hubei, Peoples R China.
通讯机构：
[Ge, JW; Mei, ZG ; Ge, JW ] H;Hunan Univ Chinese Med, Coll Integrated Tradit Chinese & Western Med, Key Lab Hunan Prov Integrated Tradit Chinese & Wes, Changsha, Hunan, Peoples R China.;Hunan Acad Tradit Chinese Med, Changsha, Hunan, Peoples R China.;China Three Gorges Univ, Grade Pharmacol Lab Chinese Med Approved 3, State Adm Tradit Chinese Med, Coll Med & Hlth Sci, Yichang 443002, Hubei, Peoples R China.
摘要：
As the only clinical thrombolytic drug approved by the FDA, tissue-type plasminogen activator (tPA) is the good standard acute treatment against ischemic stroke (IS) during the super-early stage. tPA forms the active principle of alteplase, a recombinant tissue-type plasminogen activator (rtPA), which is well known for its intravascular thrombolytic activity. However, the multifaceted functions of tPA in the central nervous system (CNS) hold untapped potential. Currently, increasing studies have explored the neuroprotective function of tPA in neurological diseases, particularly in acute ischemic stroke (AIS). A series of studies have indicated that tPA has anti-excitotoxic, neurotrophic, and anti-apoptotic effects on neurons; it is also involved in neuronal plasticity, axonal regeneration, and cerebral inflammatory processes, but how to deeply understand the underlying mechanism and take maximum advantage of tPA seems to be urgent. Therefore, more work is needed to illuminate how tPA performs with more diverse functions after stroke onset. In this comment, we focus on possible hypotheses about why and how tPA promotes ischemic neuronal survival in a comprehensive view. The text provides a holistic picture of the functions of tPA and enlists the considerations for the future, which might attract more attention toward the therapeutic potential of tPA in AIS.
期刊：
Frontiers in Cellular Neuroscience,2023年17:1191629 ISSN：1662-5102
通讯作者：
Ge, Jinwen;Mei, ZG;Ge, JW
作者机构：
[She, Ruining; Ge, Jinwen; Mei, Zhigang; Wang, Guozuo] Hunan Univ Chinese Med, Coll Integrated Tradit Chinese & Western Med, Key Lab Hunan Prov Integrated Tradit Chinese & Wes, Changsha, Hunan, Peoples R China.;[Liu, Danhong; Liao, Jun] Hunan Univ Chinese Med, Med Sch, Changsha, Hunan, Peoples R China.;[Ge, Jinwen] Hunan Acad Tradit Chinese Med, Changsha, Hunan, Peoples R China.;[Mei, Zhigang] China Three Gorges Univ, Third Grade Pharmacol Lab Chinese Med Approved Sta, Yichang, Hubei, Peoples R China.
通讯机构：
[Ge, JW; Mei, ZG ; Ge, JW ] H;Hunan Univ Chinese Med, Coll Integrated Tradit Chinese & Western Med, Key Lab Hunan Prov Integrated Tradit Chinese & Wes, Changsha, Hunan, Peoples R China.;Hunan Acad Tradit Chinese Med, Changsha, Hunan, Peoples R China.;China Three Gorges Univ, Third Grade Pharmacol Lab Chinese Med Approved Sta, Yichang, Hubei, Peoples R China.
摘要：
Ischemic stroke (IS) accounts for more than 80% of the total stroke, which represents the leading cause of mortality and disability worldwide. Cerebral ischemia/reperfusion injury (CI/RI) is a cascade of pathophysiological events following the restoration of blood flow and reoxygenation, which not only directly damages brain tissue, but also enhances a series of pathological signaling cascades, contributing to inflammation, further aggravate the damage of brain tissue. Paradoxically, there are still no effective methods to prevent CI/RI, since the detailed underlying mechanisms remain vague. Mitochondrial dysfunctions, which are characterized by mitochondrial oxidative stress, Ca2+ overload, iron dyshomeostasis, mitochondrial DNA (mtDNA) defects and mitochondrial quality control (MQC) disruption, are closely relevant to the pathological process of CI/RI. There is increasing evidence that mitochondrial dysfunctions play vital roles in the regulation of programmed cell deaths (PCDs) such as ferroptosis and PANoptosis, a newly proposed conception of cell deaths characterized by a unique form of innate immune inflammatory cell death that regulated by multifaceted PANoptosome complexes. In the present review, we highlight the mechanisms underlying mitochondrial dysfunctions and how this key event contributes to inflammatory response as well as cell death modes during CI/RI. Neuroprotective agents targeting mitochondrial dysfunctions may serve as a promising treatment strategy to alleviate serious secondary brain injuries. A comprehensive insight into mitochondrial dysfunctions-mediated PCDs can help provide more effective strategies to guide therapies of CI/RI in IS.
作者机构：
[Peng, Mingjing; He, Zhuo; Wang, Jinfeng; Deng, Shun; Chen, Zhuo; Zuo, Chaohui] Hunan Canc Hosp, Translat Med Joint Res Ctr Liver Canc, Dept Gastroduodenal & Pancreat Surg, Lab Digest Oncol, Changsha 410013, Hunan, Peoples R China.;[Peng, Mingjing; He, Zhuo; Wang, Jinfeng; Deng, Shun; Chen, Zhuo; Zuo, Chaohui] Cent South Univ, Affiliated Canc Hosp, Clin Res Ctr Tumor Pancreaticobiliary Duodenal Jun, Xiangya Sch Med, Changsha 410013, Hunan, Peoples R China.;[Deng, Rilin; Zhu, Haizhen] Hunan Univ, Inst Pathogen Biol & Immunol, Coll Biol, State Key Lab Chemo Biosensing & Chemometr, Changsha 410082, Hunan, Peoples R China.;[Chen, Shuai; Chen, Zhuo; Zuo, Chaohui] Hunan Univ Chinese Med, Sch Integrated Tradit Chinese & Western Med, Changsha 410208, Hunan, Peoples R China.;[Xu, Biaoming; Hu, Qi; Chen, Zhuo; Zuo, Chaohui] Univ South China, Grad Sch, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Zuo, CH ] H;Hunan Canc Hosp, Translat Med Joint Res Ctr Liver Canc, Dept Gastroduodenal & Pancreat Surg, Lab Digest Oncol, Changsha 410013, Hunan, Peoples R China.;Cent South Univ, Affiliated Canc Hosp, Clin Res Ctr Tumor Pancreaticobiliary Duodenal Jun, Xiangya Sch Med, Changsha 410013, Hunan, Peoples R China.;Hunan Univ Chinese Med, Sch Integrated Tradit Chinese & Western Med, Changsha 410208, Hunan, Peoples R China.;Univ South China, Grad Sch, Hengyang 421001, Hunan, Peoples R China.
关键词：
Cancer;Gastroenterology;Microbiology
摘要：
Cytotoxin-associated gene A (CagA) of Helicobacter pylori (Hp) may promote immune evasion of Hp-infected gastric cancer (GC), but potential mechanisms are still under explored. In this study, the positive rates of CagA and PD-L1 protein in tumor tissues and the high level of exosomal PD-L1 protein in plasma exosomes were significantly associated with the elevated stages of tumor node metastasis (TNM) in Hp-infected GC. Moreover, the positive rate of CagA was positively correlated with the positive rate of PD-L1 in tumor tissues and the level of PD-L1 protein in plasma exosomes, and high level of exosomal PD-L1 might indicate poor prognosis of Hp-infected GC. Mechanically, CagA increased PD-L1 level in exosomes derived from GC cells by inhibiting p53 and miRNA-34a, suppressing proliferation and anticancer effect of CD8(+) Tcells. This study provides sights for understanding immune evasion mediated by PD-L1. Targeting CagA and exosomal PD-L1 may improve immunotherapy efficacy of Hp-infected GC.
摘要：
Network pharmacology and bioinformatics were used to study puerarin's molecular mechanism in treating osteoarthritis from the perspective of ferroptosis, revealing a new treatment target. Ferroptosis-related targets were obtained from FerrDb. Puerarin action targets were retrieved from TCMSP, Pharmmappe, SwissTargetPrediction, and Targetnet databases, and supplemented with PubMed. The gene expression profiles of GSE12021, GSE55235, and GSE82107 were obtained using "Osteoarthritis" as the search term in the GEO database, and the differential expression gene screening analysis was performed for osteoarthritis. The intersection targets between puerarin, iron death, and osteoarthritis were obtained using Venn diagrams. GO and KEGG analyses were conducted with R software. Molecular docking and visualization of puerarin and core targets were performed using Autodock Vina and PyMol software. The effects of puerarin on the cell viability and the TNFα, IL6, and Ilβ levels of human inflammation articular chondrocytes were tested in vitro experiments. Puerarin, ferroptosis, and osteoarthritis share four targets: PLIN2, PTGS2, VEGFA, and IL6. GO enrichment analysis showed that puerarin maintained the blood-brain barrier, regulated peptide serine phosphorylation, and had anti-inflammatory effects. KEGG analysis showed that puerarin's anti-inflammatory effects were mainly through VEGF, IL-17, C-type lectin receptor, HIF-1, TNF, and other signaling pathways. Puerarin closely bound PLIN2, PTGS2, VEGFA, and IL6 targets in molecular docking. In vitro, puerarin prevented osteoarthritis. Network pharmacology and bioinformatics explained puerarin's multi-target and multi-pathway treatment of OA, which may be related to ferroptosis, and confirmed its anti-inflammatory effect.
期刊：
Journal of Clinical Gastroenterology,2023年57(8):782-788 ISSN：0192-0790
通讯作者：
Tian, XF
作者机构：
[Huang, Caizhi; Tian, Xuefei; Tian, XF] Hunan Univ Chinese Med, Coll Integrated Chinese & Western Med, Dept Internal Med, Changsha, Peoples R China.;[Huang, Caizhi] Hunan Childrens Hosp, Dept Lab Med, Changsha, Peoples R China.;[Mei, Si] Hunan Univ Chinese Med, Dept Physiol, Changsha, Peoples R China.;[Zhang, Xue] Hunan Univ Chinese Med, Key Lab Tradit Chinese Med Mech Tumor Prevent & Tr, Changsha, Peoples R China.;[Tian, Xuefei; Tian, XF] Hunan Univ Chinese Med, Hunan Prov Univ, Key Lab Oncol Tradit Chinese Med, Changsha, Hunan, Peoples R China.
通讯机构：
[Tian, XF ] H;Hunan Univ Chinese Med, Coll Integrated Chinese & Western Med, Dept Internal Med, Changsha, Peoples R China.;Hunan Univ Chinese Med, Hunan Prov Univ, Key Lab Oncol Tradit Chinese Med, Changsha, Hunan, Peoples R China.
关键词：
gut microbiota, hepatocellular carcinoma, inflammation, dysbiosis
摘要：
Hepatocellular carcinoma (HCC) is an invasive primary liver cancer caused by multiple pathogenic factors and is a significant global health concern. With few effective therapeutic options, HCC is a heterogeneous carcinoma that typically arises in an inflammatory environment. Recent studies have suggested that dysbiotic gut microbiota is involved in hepatocarcinogenesis via multiple mechanisms. In this review, we discuss the effects of gut microbiota, microbial components, and microbiota-derived metabolites on the promotion and progression of HCC by feeding a persistent inflammatory milieu. In addition, we discuss the potential therapeutic modalities for HCC targeting the inflammatory status induced by gut microbiota. A better understanding of the correlation between the inflammatory milieu and gut microbiota in HCC may be beneficial for developing new therapeutic strategies and managing the disease.
摘要：
ETHNOPHARMACOLOGICAL RELEVANCE: The traditional Chinese herbal formula Xuefu Zhuyu decoction (XFZYD) is a classic formula in the category of invigorating blood circulation and resolving blood stasis. It has been proven to improve the neurological and ethological prognosis of traumatic brain injury. XFZYD promotes synaptic and axonal regeneration after traumatic brain injury, which is functionally modulated by the N(6)-methyladenosine (m(6)A) modification of RNA. However, the epigenetic effects of XFZYD on m(6)A modification remain unknown. AIM OF THE STUDY: To explore how XFZYD protects against traumatic brain injury induced by controlled cortical impact (CCI) injury by altering RNA m(6)A modification. MATERIALS AND METHODS: The modified neurological severity scoring and Morris water maze were performed to evaluate the neuroprotective effects of XFZYD for 14 days and screen the dose. Then, dot blot, western blotting, and methylated RNA immunoprecipitation sequencing (MeRIP-Seq) were used to explore changes in RNA m(6)A modification in the perilesional cortex. The Metascape platform was used to analyze the Gene Ontology, Kyoto Encyclopedia of Genes and Genomes (KEGG), and Reactome pathway of the differential m(6)A-tagged genes. Furthermore, MeRIP-qPCR was conducted to quantify differences in the hub differential m(6)A modification gene brain-derived neurotrophic factor (Bdnf). RESULTS: XFZYD significantly ameliorated the neurological deficits, spatial learning, and memory impairments in rats post-CCI on day 14. XFZYD enhanced the m(6)A level, and the expression of METTL14 and YTHDC2 in the perilesional cortex of CCI rats. In all three groups, the 3'-untranslated regions and coding sequence were primarily enriched for m(6)A peaks. XFZYD reversed the increased proportion of 3'-untranslated regions, and the decreased proportion of coding sequence and 5'-untranslated regions post-CCI. Moreover, XFZYD markedly downregulated 41 elevated m(6)A-tagged transcripts and upregulated 119 decreased m(6)A-tagged transcripts following CCI. Gene ontology and KEGG pathway analysis revealed that XFZYD-regulated m(6)A-tagged transcripts were predominantly enriched in synapse assembly, synaptic plasticity, learning or memory, and MAPK signaling pathway. Then, the hub-regulated m(6)A-tagged gene BDNF was identified. Both the m(6)A methylation level and the protein level of BDNF were ascended by XFZYD treatment. CONCLUSION: XFZYD improves neurological deficits, spatial learning and memory impairments in rats post-TBI probably through increasing the expression of METTL14 and BDNF in the cortex. Our study highlights a novel post-transcriptional regulation mechanism mediated by herbal medicine for traumatic brain injury treatment.
期刊：
Frontiers in Pharmacology,2023年14 ISSN：1663-9812
通讯作者：
Zhang, SF
作者机构：
[Ou, Qinling; Zhang, SF; Yan, Haixia; Zhang, Sifang; Chang, Yonglong; Nie, Kechao; Li, Jing] Cent South Univ, Second Xiangya Hosp, Dept Integrated Tradit Chinese & Western Med, Changsha, Peoples R China.;[Ou, Qinling; Zhang, SF; Zhang, Sifang] Natl Clin Res Ctr Metab Dis, Changsha, Peoples R China.;[Zhou, Xuhui] Brain Hosp Hunan Prov, Peoples Hosp Hunan Prov 2, Hunan Inst Mental Hlth, Dept Addict Med, Changsha, Peoples R China.;[Liu, Jinhui] Hunan Univ Chinese Med, Coll Integrated Tradit Chinese & Western Med, Changsha, Peoples R China.
通讯机构：
[Zhang, SF ] C;Cent South Univ, Second Xiangya Hosp, Dept Integrated Tradit Chinese & Western Med, Changsha, Peoples R China.;Natl Clin Res Ctr Metab Dis, Changsha, Peoples R China.
摘要：
Background: Colorectal cancer (CRC) is a prevalent malignancy affecting the digestive tract, and its incidence has been steadily rising over the years. Surgery remains the primary treatment modality for advanced colorectal cancer, complemented by chemotherapy. The development of drug resistance to chemotherapy is a significant contributor to treatment failure in colorectal cancer. Nanodrug delivery systems (NDDS) can significantly improve the delivery and efficacy of antitumor drugs in multiple ways. However, there is a lack of visualization of NDDS research structures and research hotspots in the field of colorectal cancer, and the elaboration of potential research areas remains to be discovered.Objective: To comprehensively explore the current research status and development trend of NDDS in CRC research.Methods: Bibliometric analysis of articles and reviews on NDDS for CRC published between 2002 and 2022 using tools including CiteSpace, VOSviewer, R-bibliometrix, and Microsoft Excel was performed.Results: A total of 1866 publications authored by 9,870 individuals affiliated with 6,126 institutions across 293 countries/regions were included in the analysis. These publications appeared in 456 journals. Abnous Khalil has the highest number of publications in this field. The most published journals are the International Journal of Nanomedicine, International Journal of Pharmaceutics, and Biomaterials. Notably, the Journal of Controlled Release has the highest citation count and the third-highest H-index. Thematic analysis identified "inflammatory bowel disease"," "oral drug delivery," and "ulcerative colitis" as areas requiring further development. Keyword analysis revealed that "ulcerative colitis," "exosomes," and "as1411"have emerged as keywords within the last 2 years. These emerging keywords may become the focal points of future research.Conclusion: Our findings reveal the current research landscape and intellectual structure of NDDS in CRC research which helps researchers understand the research trends and hot spots in this field.
作者机构：
[Long, Chunjiao; Liu, Chi; Qu, Xiangping; Liu, Huijun; Qin, Xiaoqun; Xiang, Yang; Ji, Ming; Liu, Lexin; Wu, Di; Zhu, Jiahui] Cent South Univ, Sch Basic Med Sci, Dept Physiol, Changsha 410008, Hunan, Peoples R China.;[Wu, Di] Foshan Univ, Sch Med, Foshan 528000, Guangdong, Peoples R China.;[Liu, Caixia] Hunan Univ Chinese Med, Sch Integrated Chinese & Western Med, Changsha 410208, Hunan, Peoples R China.
通讯机构：
[Xiang, Y ] C;Cent South Univ, Sch Basic Med Sci, Dept Physiol, Changsha 410008, Hunan, Peoples R China.
关键词：
CTNNAL1;Glucocorticoid sensitivity;Asthma;House dust mite;Heat shock protein 90
摘要：
AIMS: Adhesion molecules play vital roles in the induction of airway hyperresponsiveness (AHR) or airway inflammation. The down-regulation of catenin alpha-like 1 (CTNNAL1) in the bronchial epithelial cells of asthma patients and mice models has been noted in our previous study. In this work, we further explore the underlying mechanism of CTNNAL1 in asthma. MAIN METHODS: We constructed a house dust mite (HDM)-induced asthma animal model on control mice and applied CTNNAL1-siRNA transfection to create CTNNAL1-deficient mice. KEY FINDINGS: We documented much more severe airway inflammation and increased leukocyte infiltration in the lungs of the CTNNAL1-deficient mice comparing to control mice, along with elevated expression of inflammatory cytokines. Dexamethasone (DEX) treatment led to less reduced inflammation in CTNNAL1-deficient mice compared with control mice. Immunoprecipitation confirmed the interaction between heat shock protein90 (hsp90) and CTNNAL1. The expression of hsp90 was upregulated after CTNNAL1 silencing. Meanwhile, the use of hsp90 inhibitor geldanamycin significantly decreased the expression of NR3C1, ICAM-1 and the ratio of p-p65/p65 in CTNNAL1-silenced 16HBE14o- cells. Both geldanamycin and DEX could function to suppress the expression of ICAM-1 and the phosphorylation level of p65. Nevertheless, the anti-inflammatory effect of DEX proved less potent than geldanamycin in the CTNNAL1-silenced group. The combined therapy of geldanamycin and DEX significantly decreased the inflammatory responses in CTNNAL1-deficient HBE cells than DEX monotherapy. SIGNIFICANCE: Our study corroborates that CTNNAL1 deficiency induced aggravated airway inflammation and rendered insensitivity to glucocorticoids via triggering hsp90 signaling pathway.
作者机构：
[Huang, Jiawang; Ma, Xinyue; Li, Ling; Liao, Zexuan; Liu, Zhuolin] Hunan Univ Chinese Med, Coll Integrated Tradit Chinese & Western Med, Changsha 410208, Peoples R China.;[Feng, Zhiying; Wang, Kangyu] Hunan Univ Chinese Med, Coll Tradit Chinese Med, Changsha 410208, Peoples R China.;[Ning, Yi; Lu, Fangguo] Hunan Univ Chinese Med, Med Sch, Changsha 410208, Peoples R China.;[Li, Ling; Liu, Zhuolin] Hunan Univ Chinese Med, Hunan Prov Key Lab Integrated Tradit Chinese & Wes, Changsha 410208, Peoples R China.
通讯机构：
[Li, L ] H;Hunan Univ Chinese Med, Coll Integrated Tradit Chinese & Western Med, Changsha 410208, Peoples R China.;Hunan Univ Chinese Med, Hunan Prov Key Lab Integrated Tradit Chinese & Wes, Changsha 410208, Peoples R China.
摘要：
Influenza is an acute viral respiratory infection that has caused high morbidity and mortality worldwide. Influenza A virus (IAV) has been found to activate multiple programmed cell death pathways, including ferroptosis. Ferroptosis is a novel form of programmed cell death in which the accumulation of intracellular iron promotes lipid peroxidation, leading to cell death. However, little is known about how influenza viruses induce ferroptosis in the host cells. In this study, based on network pharmacology, we predicted the mechanism of action of Maxing Shigan decoction (MXSGD) in IAV-induced ferroptosis, and found that this process was related to biological processes, cellular components, molecular function and multiple signaling pathways, where the hypoxia inducible factor-1(HIF-1) signaling pathway plays a significant role. Subsequently, we constructed the mouse lung epithelial (MLE-12) cell model by IAV-infected in vitro cell experiments, and revealed that IAV infection induced cellular ferroptosis that was characterized by mitochondrial damage, increased reactive oxygen species (ROS) release, increased total iron and iron ion contents, decreased expression of ferroptosis marker gene recombinant glutathione peroxidase 4 (GPX4), increased expression of acyl-CoA synthetase long chain family member 4 (ACSL4), and enhanced activation of hypoxia inducible factor-1 alpha (HIF-1 alpha), induced nitric oxide synthase (iNOS) and vascular endothelial growth factor (VEGF) in the HIF-1 signaling pathway. Treatment with MXSGD effectively reduced intracellular viral load, while reducing ROS, total iron and ferrous ion contents, repairing mitochondrial results and inhibiting the expression of cellular ferroptosis and the HIF-1 signaling pathway. Finally, based on animal experiments, it was found that MXSGD effectively alleviated pulmonary congestion, edema and inflammation in IAV-infected mice, and inhibited the expression of ferroptosis-related protein and the HIF-1 signaling pathway in lung tissues.
摘要：
Hepatocellular carcinoma (HCC) has high morbidity and mortality, and effective therapies are lacking. Gallic acid (GA), a natural phenolic compound derived from plants, has been reported to prevent the onset and progression of various cancers. However, there is limited elaboration on the potential mechanisms and anticancer effects of GA on hepatocellular carcinoma. Inducing ferroptosis of tumor cells has become one of the most promising ways to eradicate tumor cells. However, the effect of GA on HCC ferroptosis remains unknown. We evaluated the impact of GA on cell viability, migration, and mitochondrial morphology in HepG2 cells. Our study identified a critical role of GA in inducing ferroptosis in HepG2 cells. Mechanistically, we found that GA could inhibit the expression of a ferroptosis-related protein SLC7A11 and GPX4 in HepG2, by blocking β-catenin transport from nuclear to the cytoplasm, thus inducing the inactivation of the Wnt/β-catenin pathway. Our study has confirmed that GA is a novel ferroptosis inducer of HC, suggesting GA could be a promising candidate for the clinical treatment of HCC.
期刊：
Frontiers in Immunology,2023年14:1209706 ISSN：1664-3224
通讯作者：
Wang, WJ;Kwak-Kim, J
作者机构：
[Chen, Zeyang] Qingdao Univ, Sch Med, Qingdao, Peoples R China.;[Chen, Zeyang; Wang, WJ; Wang, Wenjuan] Shanghai Jiao Tong Univ, Reprod Med Ctr, Xinhua Hosp, Sch Med, Shanghai, Peoples R China.;[Zhang, Yanan] Hunan Univ Chinese Med, Sch Integrated Chinese & Western Med, Changsha, Peoples R China.;[Kwak-Kim, Joanne] Rosalind Franklin Univ Med & Sci, Chicago Med Sch, Clin Sci Dept, Reprod Med & Immunol,Obstet & Gynecol, Vernon Hills, IL 60064 USA.;[Kwak-Kim, Joanne] Rosalind Franklin Univ Med & Sci, Ctr Canc Cell Biol, Chicago Med Sch, Immunol & Infect, N Chicago, IL 60064 USA.
通讯机构：
[Kwak-Kim, J ] R;[Wang, WJ ] S;Shanghai Jiao Tong Univ, Reprod Med Ctr, Xinhua Hosp, Sch Med, Shanghai, Peoples R China.;Rosalind Franklin Univ Med & Sci, Chicago Med Sch, Clin Sci Dept, Reprod Med & Immunol,Obstet & Gynecol, Vernon Hills, IL 60064 USA.;Rosalind Franklin Univ Med & Sci, Ctr Canc Cell Biol, Chicago Med Sch, Immunol & Infect, N Chicago, IL 60064 USA.
关键词：
memory regulatory T cells;reproductive immunology;Pregnancy;Recurrent pregnancy loss;gestational diabetes mellitus;Preeclampsia
摘要：
Pregnancy requires the process of maternal immune tolerance to semi-allogeneic embryos. In contrast, an overreactive maternal immune system to embryo-specific antigens is likely to result in the rejection of embryos while damaging the invading placenta, such that the likelihood of adverse pregnancy outcomes can be increased. Regulatory T cells (Tregs) are capable of suppressing excessive immune responses and regulating immune homeostasis. When stimulating Tregs, specific antigens will differentiate into memory Tregs with long-term survival and rapid and powerful immune regulatory ability. Immunomodulatory effects mediated by memory Tregs at the maternal-fetal interface take on critical significance in a successful pregnancy. The impaired function of memory Tregs shows a correlation with various pregnancy complications (e.g., preeclampsia, gestational diabetes mellitus, and recurrent pregnancy losses). However, the differentiation process and characteristics of memory Tregs, especially their role in pregnancy, remain unclear. In this study, a review is presented in terms of memory Tregs differentiation and activation, the characteristics of memory Tregs and their role in pregnancy, and the correlation between memory Tregs and pregnancy complications. Furthermore, several potential therapeutic methods are investigated to restore the function of memory Tregs in accordance with immunopathologies arising from memory Tregs abnormalities and provide novel targets for diagnosing and treating pregnancy-associated diseases.
作者机构：
[Yu Yi-Pin; Sheng Dan; Zhong Li-Qin; Tan Duo-Ting] Hunan Univ Chinese Med, Grad Sch, Changsha 410208, Peoples R China.;[Liang, H; Hu Zhi-Xi; Liang Hao; Yang Liu] Hunan Univ Chinese Med, Inst TCM Diagnost, Changsha 410208, Peoples R China.;[Huang Ru-Jia] Hunan Univ Chinese Med, Sch Integrated Chinese & Western Med, Changsha 410208, Peoples R China.
通讯机构：
[Liang, H ] H;Hunan Univ Chinese Med, Inst TCM Diagnost, Changsha 410208, Peoples R China.
