摘要：
INTRODUCTION: Innate and acquired chemoresistance in colorectal cancer (CRC) often results in 5-fluorouracil (5-FU) treatment failure. This study aimed to investigate the potential of Jianpi Jiedu (JPJD) decoction to reverse 5-FU resistance in CRC and clarify its potential mechanism of action. METHODS: The CCK-8 assay was employed to assess cell activity. Flow cytometry was employed to assess various parameters including cell apoptosis, cell cycle distribution, P-glycoprotein (P-gp) activity, reactive oxygen species levels, and lipid peroxidation. Metabolomics analysis was conducted to identify differentially expressed metabolites. Western blotting was utilized for protein expression analysis. RESULTS: In this study, we demonstrated that the combined JPJD and 5-FU treatment reversed 5-FU resistance in HCT8/5-FU cells, inducing cell apoptosis, causing G2/M-phase cell cycle arrest, and reducing P-gp protein expression and activity. Metabolomics analysis revealed ferroptosis as a key pathway in the development of 5-FU resistance. Furthermore, the combination treatment reversed drug resistance primarily by impacting ferroptosis and triggering critical ferroptosis events through the suppression of the cystine/glutamate transporter (xCT)/glutathione (GSH)/glutathione peroxidase (GPX4) axis. CONCLUSION: JPJD decoction primarily suppressed the xCT/GSH/GPX4 axis to trigger ferroptosis, thereby effectively reversing 5-FU resistance in colorectal cancer (CRC).
关键词：
Acute toxicity;Behavioral analysis;Danggui Shaoyao San;Danio rerio;Histopathological alteration index
摘要：
ETHNOPHARMACOLOGICAL RELEVANCE: Although the Traditional Chinese Medicine (TCM) prescription of Danggui Shaoyao San (DSS) presents substantial clinical efficacy and promising clinical prospects, the safety of DSS and its extracts have been inadequately investigated. The larva-adult duality of the zebrafish model offers a more efficient approach for evaluating the safety of herbal preparations in the fields of toxicology and pharmacology. AIM OF THE STUDY: To investigate the acute toxicity of the extract derived from Danggui Shaoyao San, a traditional Chinese medicine preparation, on both Danio rerio embryos and adult organisms. MATERIALS AND METHODS: The components of DSS were identified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The hatching rate of Danio rerio juveniles with different concentrations of DSS was calculated and the morphological changes of juveniles after administration were observed through a microscope. The behavioral trajectory of the adult fish was recorded by the observation tower of the automated Danio rerio analysis system, and DSS's effects on the behavior was analyzed. The pathological changes of Danio rerio gills, livers, kidneys, intestines and spermaries were examined using HE staining. RESULTS: Compared with the control group, 25, 50 and 100mg/L of DSS did not elicit any significant impacts on the hatching rate and morphology. Both 200mg/L and the propylene glycol 2% reduced the hatching rate and caused the morphological teratogenic changes of the juvenile fish. The dosage of DSS below 100mg/L had no discernible effect on the behavior of the adult fish, whereas the application of propylene glycol 2% was found to stimulate the adult fish, resulting in a notable increase in high-speed movement distance. 100mg/L DSS group was not observed to cause any noticeable damage to the gills, livers, intestines and spermaries of Danio rerio, only mild nephrotoxicity was detected. The propylene glycol 2% group was found to result in pathological changes such as hyperplasia of epithelial cells on secondary lamellae, liver cell outline loss or atypia, tubal disorganization, goblet cell hypertrophy and irregularly arranged spermatozoa. CONCLUSION: A viable approach for conducting toxicological studies on TCM preparations was developed and tested in this research. The findings showed that Danggui Shaoyao San has minimal acute toxicity to embryos and adult organisms at concentrations up to 100mg/L. These results indicate that Danggui Shaoyao San is a safe TCM preparation.
摘要：
A549 cells were treated with different concentrations of anlotinib to create anlotinib‐resistant A549 cells (A549/anlotinib cells). miR‐181a‐3p mimics were transfected into A549/anlotinib cells. Meanwhile, A549 and A549/anlotinib cells were treated with β‐sitosterol at different concentrations. Cell Counting Kit‐8 (CCK‐8) was used to measure cell proliferation. The apoptosis level was detected by flow cytometry. Real‐time fluorescence quantitative PCR was used to detect the expression of miR‐181a‐3p. miR‐181a‐3p interaction with H/ACA ribonucleoprotein assembly factor (SHQ1) was predicted by miRDB and TargetScan Human databases and verified by luciferase reporter assay. The expressions of SHQ1, activating transcription factor 6 (ATF6) and glucose regulated protein 78 (GRP78) were detected by western blot. Our results show that β‐Sitosterol markedly promoted anlotinib‐resistant A549 cells apoptosis and inhibited the cell proliferation via activating SHQ1/UPR signaling via inhibiting miR‐181a‐3p. Abstract Anlotinib is used for the treatment of advanced non‐small cell lung cancer; however, the emergence of drug resistance limits its clinical application. β‐sitosterol may also be used to treat lung cancer, but there have been no studies evaluating β‐sitosterol against anlotinib‐resistant lung cancer. The purpose of this study was to determine the mechanism by which β‐sitosterol enhances the sensitivity of lung cancer cells to anlotinib. A549 cells were treated with different concentrations of anlotinib to generate anlotinib‐resistant cells (A549/anlotinib cells). miR‐181a‐3p mimics were transfected into A549/anlotinib cells. A549 and A549/anlotinib cells were treated with β‐sitosterol at various concentrations. The Cell Counting Kit‐8 (CCK‐8) assay was used to measure cell proliferation. Apoptosis was assessed by flow cytometry. Real‐time quantitative PCR was used to measure the expression of miR‐181a‐3p. The interaction of miR‐181a‐3p with the H/ACA ribonucleoprotein assembly factor (SHQ1) was predicted using the miRDB and TargetScan Human databases and verified with a luciferase reporter assay. The expression of SHQ1, activating transcription factor 6 (ATF6), and glucose‐regulated protein 78 (GRP78) were measured by western blot analysis. β‐Sitosterol effectively suppressed A549/anlotinib cell proliferation and promoted apoptosis. SHQ1 is a downstream target of miR‐181a‐3p. The expression of miR‐181a‐3p was inhibited; however, SHQ1 expression was increased by β‐sitosterol treatment of A549/anlotinib cells. The inhibition of SHQ1, ATF6, and GRP78 protein expression by β‐sitosterol in A549/anlotinib cells was rescued by increased miR‐181a‐3p. β‐Sitosterol markedly promotes anlotinib‐resistant A549 cell apoptosis and inhibits cell proliferation by activating SHQ1/UPR signaling through miR‐181a‐3p inhibition.
作者机构：
[Wu, Qin; Zhang, Ya-nan] Hunan Univ Chinese Med, Sch Integrated Chinese & Western Med, Changsha 410208, Hunan, Peoples R China.;[Deng, YH; Deng, Yi-hui] Hunan Univ Chinese Med, Sch Chinese Med, Changsha 410208, Hunan, Peoples R China.
通讯机构：
[Deng, YH ] H;Hunan Univ Chinese Med, Sch Chinese Med, Changsha 410208, Hunan, Peoples R China.
摘要：
Gestational diabetes mellitus (GDM) is a common complication that occurs during pregnancy. Emerging evidence suggests that immune abnormalities play a pivotal role in the development of GDM. Specifically, regulatory T cells (Tregs) are considered a critical factor in controlling maternal-fetal immune tolerance. However, the specific characteristics and alterations of Tregs during the pathogenesis of GDM remain poorly elucidated. Therefore, this study aimed to investigate the changes in Tregs among pregnant women diagnosed with GDM compared to healthy pregnant women. A prospective study was conducted, enrolling 23 healthy pregnant women in the third trimester and 21 third-trimester women diagnosed with GDM. Participants were followed up until the postpartum period. The proportions of various Treg, including Tregs, mTregs, and nTregs, were detected in the peripheral blood of pregnant women from both groups. Additionally, the expression levels of PD-1, HLA-G, and HLA-DR on these Tregs were examined. The results revealed no significant differences in the proportions of Tregs, mTregs, and nTregs between the two groups during the third trimester and postpartum period. However, GDM patients exhibited significantly reduced levels of PD-1(+) Tregs (P < 0.01) and HLA-G(+) Tregs (P < 0.05) in the third trimester compared to healthy pregnant women in the third trimester. Furthermore, GDM patients demonstrated significantly lower levels of PD-1(+) mTregs (P < 0.01) and HLA-G(+) (P < 0.05) mTregs compared to healthy pregnant women in the third trimester. Overall, the proportion of Tregs did not exhibit significant changes during the third trimester in GDM patients compared to healthy pregnant women. Nevertheless, the observed dysregulation of immune regulation function in Tregs and mTregs may be associated with the development of GDM in pregnant women.
摘要：
Immunotherapy, particularly immune checkpoint inhibitor (ICIs) therapy, stands as an innovative therapeutic approach currently garnering substantial attention in cancer treatment. It has become a focal point of numerous studies, showcasing significant potential in treating malignancies, including lung cancer and melanoma. The objective of this research is to analyze publications regarding immunotherapy for colorectal cancer (CRC), investigating their attributes and identifying the current areas of interest and cutting-edge advancements. We took into account the publications from 2002 to 2022 included in the Web of Science Core Collection. Bibliometric analysis and visualization were conducted using CiteSpace, VOSviewer, R-bibliometrix, and Microsoft Excel. The quantity of publications associated with this domain has been steadily rising over the years, encompassing 3753 articles and 1498 reviews originating from 573 countries and regions, involving 19,166 institutions, 1011 journals, and 32,301 authors. In this field, China, the United States, and Italy are the main countries that come forward for publishing. The journal with the greatest impact factor is CA-A Cancer Journal for Clinicians. Romain Cohen leads in the number of publications, while Le Dt stands out as the most influential author. The immune microenvironment and immune infiltration are emerging as key hotspots and future research directions in this domain. This research carries out an extensive bibliometric examination of immunotherapy for colorectal cancer, aiding researchers in understanding current focal points, investigating possible avenues for research, and recognizing forthcoming development trends.
作者机构：
[Yang, Renyi; Zeng, Puhua; Jian, Huiying; Xue, Peisen; Li, Kexiong; Li, KX; Yu, Xiaopeng; Peng, Wei; Peng, W] Hunan Acad Chinese Med, Hunan Prov Hosp Integrated Tradit Chinese & Wester, Canc Res Inst, Hunan Acad Tradit Chinese Med, Changsha 410006, Hunan, Peoples R China.;[Gao, Wenhui; Peng, Lian] Hunan Univ Chinese Med, Sch Tradit Chinese Med, Changsha 410208, Hunan, Peoples R China.;[Wang, Zhibing] Hunan Univ Chinese Med, Sch Integrated Chinese & Western Med, Key Lab Hunan Prov Integrated Tradit Chinese & Wes, Changsha 410208, Hunan, Peoples R China.
通讯机构：
[Li, KX; Zeng, PH ; Peng, W] H;Hunan Acad Chinese Med, Hunan Prov Hosp Integrated Tradit Chinese & Wester, Canc Res Inst, Hunan Acad Tradit Chinese Med, Changsha 410006, Hunan, Peoples R China.
关键词：
Ferroptosis;Hepatocellular carcinoma;Mitochondrial dysfunction;Nrf2/HO-1/GPX4 axis;Polyphyllin I
摘要：
BACKGROUND: Ferroptosis is an emerging iron-dependent programmed cell death mode characterized by lipid peroxidation and iron accumulation, closely associated with Hepatocellular Carcinoma (HCC) progression. Although the impact of Polyphyllin I (PPI), a prominent bioactive constituent derived from Paris polyphylla, on diverse malignancies has been established, the specific role and potential mechanistic pathways through which PPI modulates ferroptosis in HCC remain elusive. PURPOSE: This study aimed to elucidate the anti-cancer properties and potential mechanisms of PPI in inducing ferroptosis and triggering mitochondrial injury in HCC. METHODS: Cell viability was assessed using CCK-8 assays. EdU proliferation and colony formation assays were employed to evaluate cell proliferation. A wound-healing assay was performed to assess cell migration. Transwell assay was utilized to evaluate cell invasion. Ferroptosis was evaluated through the utilization of a FerroOrange fluorescent probe, malondialdehyde (MDA) and reduced glutathione (GSH) assay kits, DCFH-DA fluorescent probe, western blotting, and transmission electron microscopy (TEM) analysis. Molecular docking, immunofluorescence, and western blotting were employed to predict and validate the binding and interaction of PPI with Nrf2, HO-1, xCT, and GPX4. Mitochondrial structure and membrane potential changes were evaluated using JC-1 and Mito Tracker Green fluorescent probes. A nude mice xenograft model was constructed to determine the inhibitory effects and the levels of ferroptosis of PPI on HCC through hematoxylin and eosin (H&E), Prussian blue reaction, immunofluorescence staining, immunohistochemistry, and western blotting analysis, in vivo. RESULTS: PPI exhibited dose-dependent inhibitory effects on the proliferation, invasion, and metastasis of HCC cells mediated by increasing reactive oxygen species (ROS) and MDA levels, promoting Fe(2+) accumulation, depleting GSH, and suppressing the expression of xCT and GPX4, thereby inducing ferroptosis in HCC. The induction of ferroptosis by PPI was associated with the binding of PPI to Nrf2, HO-1, and GPX4 proteins, modulating the Nrf2/HO-1/GPX4 antioxidant axis. PPI also induced mitochondrial structural damage and decreased mitochondrial membrane potential (MMP). Inhibition of ferroptosis by ferrostatin-1 (Fer-1) mitigated the mitochondrial disruption induced by PPI. In vivo, PPI inhibited Nrf2/HO-1/GPX4 axis-induced ferroptosis, impeding HCC growth similar to the effects of sorafenib. CONCLUSION: These results demonstrated that PPI intervention can suppress the proliferation, invasion, and metastasis of HCC cells by enhancing mitochondrial disruption and inducing ferroptosis via the Nrf2/HO-1/GPX4 axis. Consequently, our research advances the frontiers of pharmacodynamics and deepens our comprehension of the intricate mechanisms underpinning PPI. Furthermore, it has yielded an innovative treatment stratagem rooted in the tenets of Traditional Chinese Medicine (TCM), thereby furnishing a novel therapeutic avenue for addressing HCC.
作者机构：
[Song, Zhenyan; Cheng, Shaowu; Wang, Yuke; Li, Ping; Cheng, SW; Luo, Rongsiqing; He, Chunxiang; He, Jiawei; Xia, Xiaofang; Lin, Fan; Hou, Mirong; Pan, Ying] Hunan Univ Chinese Med, Sch Integrated Chinese & Western Med, Changsha 410208, Hunan, Peoples R China.;[Song, Zhenyan; Cheng, Shaowu; Wang, Yuke; Li, Ping; Cheng, SW; Luo, Rongsiqing; He, Chunxiang; He, Jiawei] Hunan Univ Chinese Med, Coll integrated Chinese & Western Med, Key Lab Hunan Prov Integrated Tradit Chinese & Wes, Changsha 410208, Hunan, Peoples R China.;[Song, Zhenyan] Natl Key Lab Cultivat Base Chinese Med Powder & In, Changsha 410208, Hunan, Peoples R China.;[He, Pan] Res Inst Zhong Nan Grain & Oil Foods, Changsha 410208, Hunan, Peoples R China.
通讯机构：
[Cheng, SW ] H;Hunan Univ Chinese Med, Sch Integrated Chinese & Western Med, Changsha 410208, Hunan, Peoples R China.;Hunan Univ Chinese Med, Coll integrated Chinese & Western Med, Key Lab Hunan Prov Integrated Tradit Chinese & Wes, Changsha 410208, Hunan, Peoples R China.
期刊：
Frontiers in Pharmacology,2024年15:1250918 ISSN：1663-9812
通讯作者：
Ge, JW
作者机构：
[Xu, Hao; Yang, Kailin; Wang, Shanshan; Ge, Jinwen] Hunan Univ Chinese Med, Sch Integrated Chinese & Western Med, Key Lab Hunan Prov Integrated Tradit Chinese & Wes, Changsha, Peoples R China.;[Yang, Kailin; Ge, Jinwen] Hunan Acad Chinese Med, Changsha, Hunan, Peoples R China.;[Zeng, Liuting] Chinese Acad Med Sci & Peking Union Med Coll, Grad Sch, Beijing, Peoples R China.;[He, Qi] Peoples Hosp Ningxiang City, Dept Crit Care Med, Ningxiang, Peoples R China.
通讯机构：
[Ge, JW ] H;Hunan Univ Chinese Med, Sch Integrated Chinese & Western Med, Key Lab Hunan Prov Integrated Tradit Chinese & Wes, Changsha, Peoples R China.;Hunan Acad Chinese Med, Changsha, Hunan, Peoples R China.
摘要：
Ischemic stroke (IS) is a major cause of mortality and disability among adults. Recanalization of blood vessels to facilitate timely reperfusion is the primary clinical approach; however, reperfusion itself may trigger cerebral ischemia-reperfusion injury. Emerging evidence strongly implicates the NLRP3 inflammasome as a potential therapeutic target, playing a key role in cerebral ischemia and reperfusion injury. The aberrant expression and function of NLRP3 inflammasome-mediated inflammation in cerebral ischemia have garnered considerable attention as a recent research focus. Accordingly, this review provides a comprehensive summary of the signaling pathways, pathological mechanisms, and intricate interactions involving NLRP3 inflammasomes in cerebral ischemia-reperfusion injury. Moreover, notable progress has been made in investigating the impact of natural plant products (e.g., Proanthocyanidins, methylliensinine, salidroside, α-asarone, acacia, curcumin, morin, ginsenoside Rd, paeoniflorin, breviscapine, sulforaphane, etc.) on regulating cerebral ischemia and reperfusion by modulating the NLRP3 inflammasome and mitigating the release of inflammatory cytokines. These findings aim to present novel insights that could contribute to the prevention and treatment of cerebral ischemia and reperfusion injury.
作者机构：
[Zeng, Puhua; Jian, Xiaolan; Peng, Wei] Hunan Acad Tradit Chinese Med, Affiliated Hosp, Changsha 410006, Peoples R China.;[Peng, Wei] Hunan Univ Tradit Chinese Med, Sch Integrated Chinese & Western Med, Changsha 410006, Peoples R China.;[Yang, Renyi; Yu, Xiaopeng] Hunan Univ Chinese Med, Changsha 410208, Hunan, Peoples R China.;[Nie, Sha] Fourth Hosp Changsha, Changsha 410006, Hunan, Peoples R China.;[Zeng, Puhua] Hunan Acad Tradit Chinese Med, Canc Res Inst, Changsha, Hunan, Peoples R China.
通讯机构：
[Zeng, PH ; Jian, XL] H;Hunan Acad Tradit Chinese Med, Affiliated Hosp, Changsha 410006, Peoples R China.;Hunan Acad Tradit Chinese Med, Canc Res Inst, Changsha, Hunan, Peoples R China.
关键词：
Postoperative patients with pancreatic cancer;Nomogram;Cancer specific survival;Prediction model;SEER database
摘要：
The recurrence rate and mortality rate among postoperative pancreatic cancer patients remain elevated. This study aims to develop and validate the cancer-specific survival period for individuals who have undergone pancreatic cancer surgery. We extracted eligible data from the Surveillance, Epidemiology, and End Results database and randomly divided all patients into a training cohort and an internal validation cohort. External validation was performed using a separate Chinese cohort. The nomogram was developed using significant risk factors identified through univariate and multivariate Cox proportional hazards regression. The effectiveness of the nomogram was assessed using the area under the time-dependent curve, calibration plots, and decision curve analysis. Kaplan–Meier survival curves were utilized to visualize the risk stratification of nomogram and AJCC stage. Seven variables were identified through univariate and multivariate analysis to construct the nomogram. The consistency index of the nomogram for predicting overall survival was 0.683 (95% CI: 0.675–0.690), 0.689 (95% CI: 0.677–0.701), and 0.823 (95% CI: 0.786–0.860). The AUC values for the 1- and 2-year time-ROC curves were 0.751 and 0.721 for the training cohort, 0.731 and 0.7554 for the internal validation cohort, and 0.901 and 0.830 for the external validation cohorts, respectively. Calibration plots demonstrated favorable consistency between the predictions of the nomogram and actual observations. Moreover, the decision curve analysis indicated the clinical utility of the nomogram, and the risk stratification of the nomogram effectively identified high-risk patients. The nomogram guides clinicians in assessing the survival period of postoperative pancreatic cancer patients, identifying high-risk groups, and devising tailored follow-up strategies.
摘要：
Background: Nasopharyngeal carcinoma (NPC) is a usual head and neck malignancy. Guggulsterone (GS) has potential in cancer chemoprophylaxis and treatment, but its therapeutic effect on NPC is unknown. We aimed to explore whether GS could promote the secretion of exosomal circFIP1L1 from NPC cells and its regulatory mechanism.<&wdkj&>Methods: NPC tissues and adjacent tissues were collected from NPC patients. Human nasopharyngeal epithelial cell lines (NP69) and NPC lines (5-8F, CNE1, and HNE1) were used for in vitro experiments. HNE1 cells were treated with GS (20, 40, 60 μmol/L). The expressions of miR-125a-5p and circFIP1L1 were evaluated by qRT-PCR. Cell proliferation and apoptosis abilities were measured by CCK-8 and flow cytometry. HNE1 cell exosomes were extracted and identified, and the levels of VEGFA and VEGFR2 were detected by ELISA. Then miR-125a-5p was knocked down and overexpressed. HUVECs angiogenesis was determined by the tube formation assay. qRT-PCR and Western blot were utilized to evaluate the expressions of VEGFA, MMP-2, MMP-9, and ICAM-1 in HUVECs.<&wdkj&>Results: miR-125a-5p was highly expressed in NPC tissues and cells. GS promoted the secretion of exosomal circFIP1L1 from HNE1 cells to affect HUVECs proliferation and angiogenesis. Overexpression of miR-125a-5p accelerated HUVECs proliferation and angiogenesis. Knocking down miR-125a- 5p inhibited VEGFA expression. In addition, exosomal circFIP1L1 sponged miR-125a-5p, inhibiting the VEGFA pathway to repress HUVECs angiogenesis.<&wdkj&>Conclusions: GS promoted exosomal circFIP1L1 in NPC cells to mediate miR-125a-5p/VEGFA axis affecting tumor angiogenesis.
摘要：
Recent studies have highlighted the significant involvement of tryptophan metabolism in the pathogenesis of Alzheimer's disease (AD). However, a comprehensive investigation of the precise role of tryptophan metabolism in the context of AD is still lacking. This study employed a bioinformatics approach to identify and validate potential tryptophan metabolism-related genes (TrpMgs) associated with AD. The discovery of TrpMgs was facilitated through the intersection of the Weighted Gene Co-expression Network Analysis (WGCNA) test and 17 known tryptophan metabolism pathways. Subsequently, the putative biological functions and pathways of the TrpMgs were elucidated using Gene Set Variation Analysis (GSVA). Furthermore, the Least Absolute Shrinkage and Selection Operator (LASSO) method was applied to identify hub genes and evaluate the diagnostic efficiency of the 5 TrpMgs in distinguishing AD. The relationship between hub TrpMgs and clinical characteristics was also investigated. Finally, in vivo verification of the five TrpMgs was performed using APP/PS1 mice. We identified 5 TrpMgs associated with AD, including propionyl-CoA carboxylase subunit beta (PCCB), TEA Domain Transcription Factor 1 (TEAD1), Phenylalanyl-TRNA Synthetase Subunit Beta (FARSB), Neurofascin (NFASC), and Ezrin (EZR). Among these genes, PCCB, FARSB, NFASC, and TEAD1 showed correlations with age. In the hippocampus of APP/PS1 mice, we observed down-regulation of FARSB, PCCB, and NFASC mRNA expressions. Furthermore, PCCB and NFASC protein expressions were also down-regulated in the cerebral cortex and hippocampus of APP/PS1 mice. Our study paves the way for future research aimed at unraveling the intricate mechanisms underlying tryptophan metabolism dysregulation in AD and its therapeutic implications.
期刊：
Journal of Cancer Research and Clinical Oncology,2023年149(12):10099-10108 ISSN：0171-5216
通讯作者：
Zeng, PH
作者机构：
[Yang, Renyi] Hunan Univ Chinese Med, Sch Integrated Tradit Chinese & Western Med, Changsha 410208, Hunan, Peoples R China.;[Yu, Xiaopeng] Hunan Univ Chinese Med, Changsha 410208, Hunan, Peoples R China.;[Zeng, Puhua] Hunan Acad Tradit Chinese Med, Canc Res Inst, Changsha 410006, Peoples R China.
通讯机构：
[Zeng, PH ] H;Hunan Acad Tradit Chinese Med, Canc Res Inst, Changsha 410006, Peoples R China.
关键词：
Hepatocellular carcinoma;Young and middle-aged male;Nomogram;Overall survival;Predict;Risk stratification
摘要：
BACKGROUND: Hepatocellular carcinoma (HCC) is the most common digestive tumor, and we aimed to develop and validate nomogram models, predicting the overall survival (OS) of young and middle-aged male patients with HCC. METHODS: We extracted eligible data from relevant patients between 2000 and 2017 from the Surveillance, Epidemiology, and End Results (SEER) database. In addition, randomly divided all patients into two groups (training and validation = 7:3). The nomogram was established using effective risk factors based on univariate and multivariate analysis. The area under the time-dependent curve, calibration plots, and decision curve analysis (DCA) were used to evaluate the effective performance of the nomogram. The risk stratifications of the nomogram and the AJCC criteria-based tumor stage were compared. RESULTS: 11 variables were selected by univariate and multivariate analysis to establish the nomogram of HCC. The AUC values of 3, 4, and 5 years of the time-ROC curve are 0.858, 0.862 and 0.859 for the training cohort, and 0.858, 0.877 and 0.869 for the validation cohort, respectively, indicating that the nomogram has a good ability of discrimination. The calibration plots showed favorable consistency between the prediction of the nomogram and actual observations in both the training and validation cohorts. In addition, the decision curve DCA showed that the nomogram was clinically useful and had better discriminative ability to recognize patients at high risk than the AJCC criteria-based tumor stage. CONCLUSION: Prognostic nomogram of young and middle-aged male patients with HCC was developed and validated to help clinicians evaluate the prognosis of patients.
摘要：
The study uses an LMJSS‐TMT‐UPLC‐MS method to spatially map amine metabolites to brain histopathological changes including neuron loss, glial cell activation, and neurogenesis. This integrated study explains the mechanisms of posttraumatic brain injury brain damage and repair. It also uncovers the therapeutic mechanisms of traditional Chinese medicine, Xuefu Zhuyu decoction. Abstract Introduction Spatial changes of amine metabolites and histopathology of the whole brain help to reveal the mechanism of traumatic brain injury (TBI) and treatment. Methods A newly developed liquid microjunction surface sampling–tandem mass tag–ultra performance liquid chromatography–mass spectrometry technique is applied to profile brain amine metabolites in five brain regions after impact‐induced TBI at the subacute stage. H&E, Nissl, and immunofluorescence staining are performed to spatially correlate microscopical changes to metabolic alterations. Then, bioinformatics, molecular docking, ELISA, western blot, and immunofluorescence are integrated to uncover the mechanism of Xuefu Zhuyu decoction (XFZYD) against TBI. Results Besides the hippocampus and cortex, the thalamus, caudate‐putamen, and fiber tracts also show differentiated metabolic changes between the Sham and TBI groups. Fourteen amine metabolites (including isomers such as L‐leucine and L‐isoleucine) are significantly altered in specific regions. The metabolic changes are well matched with the degree of neuronal damage, glia activation, and neurorestoration. XFZYD reverses the dysregulation of several amine metabolites, such as hippocampal Lys‐Phe/Phe‐Lys and dopamine. Also, XFZYD enhances post‐TBI angiogenesis in the hippocampus and the thalamus. Conclusion This study reveals the local amine‐metabolite and histological changes in the subacute stage of TBI. XFZYD may promote TBI recovery by normalizing amine metabolites and spatially promoting dopamine production and angiogenesis.
作者机构：
[Sheng, Wen] Hunan Univ Chinese Med, Coll Tradit Chinese Med, Changsha 410000, Peoples R China.;[Lu, Baowei; Sheng, Wen; Liu, Lumei; Ding, Jin; He, Qinghu] Hunan Univ Chinese Med, Androl Lab, Changsha 410000, Peoples R China.;[Xu, Wenjing] Hunan Univ Chinese Med, Affiliated Hosp 1, Dept Dermatol, Changsha 410000, Peoples R China.;[Ding, Jin] Guangzhou Univ Tradit Chinese Med, Affiliated Baoan Hosp Tradit Chinese Med, Clin Med Coll 7, Dept Androl, Shenzhen 518000, Peoples R China.;[Lu, Baowei; Liu, Lumei] Hunan Univ Chinese Med, Coll Integrated Tradit Chinese & Western Med, Changsha 410000, Peoples R China.
通讯机构：
[Zhou, Q ; He, QH ] H;Hunan Univ Chinese Med, Androl Lab, Changsha 410000, Peoples R China.;Hunan Univ Med, Coll Tradit Chinese Med, Changsha 410000, Peoples R China.;Hunan Univ Chinese Med, Hosp 1, Dept Androl, Changsha 410000, Peoples R China.
关键词：
Colla Carapacis et Plastri;Fecal microbiota transplantation;Male infertility;Gut microbiota;Spermatogenesis ability
摘要：
[ABSTRACT] Male infertility is a significant cause of psychosocial and marital distress in approximately 50% of couples who are unable to conceive, with male factors being the underlying cause. Guijiajiao (Colla Carapacis et Plastri, CCP) is a Traditional Chinese Medicine commonly used to treat male infertility. The present study aimed to investigate the potential mechanisms underlying the preventive effects of CCP on male infertility. An infertile male rat model was established using cyclophosphamide (CTX), and CCP was administered for both treatment and prevention. Fecal microbiota transplantation (FMT) was also performed to explore the role of gut microbiota in the CCP-mediated prevention of male infertility in rats. Sperm motility and concentration were determined using a semiautomatic sperm classification analyzer. Subsequently, histopathological analysis using HE staining was performed to examine the changes in the small intestine and testis. Moreover, the serum levels of lipopolysaccharide (LPS) and testosterone were measured by ELISA. In addition, immunohistochemistry was conducted to detect CD3 expression in the small intestine, while RT-qPCR was employed to assess the expressions of interleukin-1 beta (IL-10), cluster of differentiation 3 (CD3), Monocyte chemoattractant protein-1 (MCP-1), and C-X-C motif chemokine ligand 10 (CXCL-10) in the small intestine and epididymis. Finally, gut microbiota was analyzed by 16S rRNA sequencing. CCP improved sperm motility, number, and concentration in CTX-induced infertile male rats. CCP increased the serum testosterone level, inhibited the immune cell infiltration of the intestinal lamina propria, and promoted the aggregation of CD3+ T cells in CTX-induced male infertility rats. CCP also inhibited the expressions of MCP-1, CXCL-10, and IL-10 in the epididymis of male infertility rats. At the genus level, CTX led to a reduction in the abundance of Lactobacillus, Clostridia_UCG.014, and Romboutsia in the intestinal tract of rats. In contrast, CCP decreased the abundance of Ruminococcus and increased the abundance of Romboutsia in infertile male rats. Additionally, FMT experiments proved that the gut microbiota of CCP-treated rats facilitated testicular tissue recovery and spermatogenesis while also reducing the serum LPS level in infertile male rats. CCP improves the spermatogenic ability of infertile male rats by restoring gut microbiota diversity and inhibiting epididymal inflammation.
摘要：
BACKGROUND: The motor symptoms in patients with Parkinson's disease (PD) are commonly preceded by gastrointestinal (GI) symptoms. The enteric nervous system (ENS) has also been reported to exhibit neuropathological characteristics of PD. OBJECTIVES: To evaluate the relationship between the incidence of parkinsonism and alteration in gut microbiota and pathogens. MATERIAL AND METHODS: Studies in different languages that evaluate the relationship between gut microorganisms and PD were included into this meta-analysis. The outcomes of these studies were analyzed using a random effects model; it was also used to calculate the mean difference (MD) with 95% confidence interval (95% CI) in order to quantify the impact of different rehabilitation techniques on clinical parameters. Dichotomous and continuous models were used for the analysis of extracted data. RESULTS: A total of 28 studies were included in our analysis. The analysis of small intestinal bacterial overgrowth showed a significant correlation with Parkinson's subjects compared with controls (p < 0.001). In addition, the presence of Helicobacter pylori (HP) infection was significantly related to the Parkinson's group (p < 0.001). On the other hand, there was a significantly higher abundance level of Bifidobacteriaceae (p = 0.008), Verrucomicrobiaceae (p < 0.001) and Christensenellaceae (p = 0.003) in Parkinson's subjects. In contrast, a significantly lower abundance levels in Parkinson's subjects were found in Faecalibacterium (p = 0.03), Lachnospiraceae (p = 0.005) and Prevotellaceae (p = 0.005). No significant difference was related to Ruminococcaceae. CONCLUSION: Parkinson's subjects showed a higher degree of alteration of gut microbiota and pathogens compared with normal human subjects. Future multicenter randomized trials are needed.
期刊：
Frontiers in Pharmacology,2023年13:4847 ISSN：1663-9812
作者机构：
[Peng, Xiwen; Shang, Hongcai; She, Ruining; Ge, Jinwen; Meng, Pan; Cheng, Shaowu; Wang, Shanshan; Fang, Rui; Wang, Xiangyuan; Lin, Hongyuan; Mei, Zhigang; Zhou, Yue] Hunan Univ Chinese Med, Sch Integrated Chinese & Western Med, Changsha, Hunan, Peoples R China.;[Ge, Jinwen; Fang, Rui] Hunan Acad Chinese Med, Inst Clin Pharmacol Chinese Mat Med, Changsha, Hunan, Peoples R China.;[Hu, Hua] Hunan Univ Chinese Med, Neurol Dept, Hosp 1, Changsha, Hunan, Peoples R China.;[Jiang, Qiling; Liu, Litao] Shaoyang Univ, Sch Food & Chem Engn, Shaoyang, Hunan, Peoples R China.;[Wu, Dahua; Xie, Yao; Xie, Le] Hunan Prov Hosp Integrated Chinese & Western Med, Hunan Acad Chinese Med Affiliated Hosp, Neurol Dept, Changsha, Hunan, Peoples R China.
关键词：
Hypertensive cerebral small vessel disease;randomized controlled trial;Chinese medicine;Naotaifang capsule;Treatment
摘要：
Background: Hypertensive cerebral small vessel disease (HT-CSVD) is a cerebrovascular clinical, imaging and pathological syndrome caused by hypertension (HT). The condition manifests with lesions in various vessels including intracranial small/arterioles, capillaries, and small/venules. Hypertensive cerebral small vessel disease has complex and diverse clinical manifestations. For instance, it can present as an acute stroke which progresses to cause cognitive decline, affective disorder, unstable gait, dysphagia, or abnormal urination. Moreover, hypertensive cerebral small vessel disease causes 25-30% of all cases of ischemic strokes and more than 50% of all cases of single or mixed dementias. The 1-year recurrence rate of stroke in cerebral small vessel disease patients with hypertension is 14%. In the early stage of development, the symptoms of hypertensive cerebral small vessel disease are concealed and often ignored by patients and even clinicians. Patients with an advanced hypertensive cerebral small vessel disease manifest with severe physical and mental dysfunction. Therefore, this condition has a substantial economic burden on affected families and society. Naotaifang (NTF) is potentially effective in improving microcirculation and neurofunction in patients with ischemic stroke. In this regard, this multicenter randomized controlled trial (RCT) aims to furtherly evaluate the efficacy and safety of naotaifang capsules on hypertensive cerebral small vessel disease. Methods: This study is a multicenter, randomized, double-blind, placebo-controlled clinical trial. A total of 388 eligible subjects were recruited from the First Hospital of Hunan University of Chinese Medicine, Hunan Academy of Chinese Medicine Affiliated Hospital, the First Hospital of Shaoyang University, the First Traditional Chinese Medicine Hospital of Changde, and Jiangmen Wuyi Hospital of Traditional Chinese Medicine from July 2020 to April 2022. After a 4-week run-in period, all participants were divided into the intervention group (represented by Y-T, N-T) and control group (represented by Y-C, N-C); using a stratified block randomized method based on the presence or absence of brain damage symptoms in hypertensive cerebral small vessel disease (represented by Y and N). The Y-T and N-T groups were administered different doses of naotaifang capsules, whereas Y-C and N-C groups received placebo treatment. These four groups received the treatments for 6 months. The primary outcome included Fazekas scores and dilated Virchow-robin spaces (dVRS) grades on magnetic resonance imaging (MRI). The secondary outcomes included the number of lacunar infarctions (LI) and cerebral microbleeds (CMB) on magnetic resonance imaging, clinical blood pressure (BP) level, traditional Chinese medicine (TCM) syndrome scores, mini-mental state examination (MMSE) scale, and safety outcomes. Fazekas scores, dilated Virchow-robin spaces grades, and the number of lacunar infarctions and cerebral microbleeds on magnetic resonance imaging were tested before enrollment and after 6 months of treatment. The clinical blood pressure level, traditional Chinese medicine syndrome scores, mini-mental state examination scale and safety outcomes were tested before enrollment, after 3-month, 6-month treatment and 12th-month follow-up respectively. Conclusion: The protocol will comfirm whether naotaifang capsules reduce Fazekas scores, dilated Virchow-robin spaces grades, and the number of lacunar infarctions and cerebral microbleeds, clinical blood pressure, increase mini-mental state examination scores, traditional Chinese medicine syndrome scores of Qi deficiency and blood stasis (QDBS), and improve the quality of life of subjects. The consolidated evidence from this study will shed light on the benefits of Chinese herbs for hypertensive cerebral small vessel disease, such as nourishing qi, promoting blood circulation and removing blood stasis, and dredging collaterals. However, additional clinical trials with large samples and long intervention periods will be required for in-depth research.
摘要：
Ischemic stroke, a primary cause of disability and the second leading cause of mortality, has emerged as an urgent public health issue. Growing evidence suggests that the Cyclic GMP-AMP synthase (cGAS)- Stimulator of interferon genes (STING) pathway, a component of innate immunity, is closely associated with microglia activation, neuroinflammation, and regulated cell death in ischemic stroke. However, the mechanisms underlying this pathway remain inadequately understood. This article comprehensively reviews the existing literature on the cGAS-STING pathway and its multifaceted relationship with ischemic stroke. Initially, it examines how various risk factors and pre-disease mechanisms such as metabolic dysfunction and senescence (e.g., hypertension, hyperglycemia, hyperlipidemia) affect the cGAS-STING pathway in relation to ischemic stroke. Subsequently, we explore in depth the potential pathophysiological relationship between this pathway and oxidative stress, endoplasmic reticulum stress, neuroinflammation as well as regulated cell death including ferroptosis and PANoptosis following cerebral ischemia injury. Finally, it suggests that intervention targeting the cGAS-STING pathway may serve as promising therapeutic strategies for addressing neuroinflammation associated with ischemic stroke. Taken together, this review concludes that targeting the microglia cGAS-STING pathway may shed light on the exploration of new therapeutic strategies against ischemic stroke.
期刊：
FRONTIERS IN ENDOCRINOLOGY,2023年14:1292011 ISSN：1664-2392
通讯作者：
Tian, XF
作者机构：
[Tian, Xuefei; Tian, XF; Chen, Yating; Liu, Mengsi; Feng, Ting] Hunan Univ Chinese Med, Sch Integrated Chinese & Western Med, Changsha, Hunan, Peoples R China.;[Tian, Xuefei; Tian, XF; Chen, Yating; Liu, Mengsi; Feng, Ting] Hunan Univ Chinese Med, Hunan Key Lab Tradit Chinese Med Prescript & Syndr, Changsha, Peoples R China.;[Tian, Xuefei; Tian, XF; Chen, Yating; Liu, Mengsi; Feng, Ting] Hunan Prov Univ Key Lab Oncol Tradit Chinese Med, Changsha, Peoples R China.;[Tian, Xuefei; Tian, XF; Chen, Yating; Liu, Mengsi; Feng, Ting] Hunan Univ Chinese Med, Key Lab Tradit Chinese Med Mech Tumor Prevent & Tr, Changsha, Peoples R China.;[Zhang, Zhen] Hunan Acad Tradit Chinese Med, Dept Oncol, Affiliated Hosp, Changsha, Peoples R China.
通讯机构：
[Tian, XF ] H;Hunan Univ Chinese Med, Sch Integrated Chinese & Western Med, Changsha, Hunan, Peoples R China.;Hunan Univ Chinese Med, Hunan Key Lab Tradit Chinese Med Prescript & Syndr, Changsha, Peoples R China.;Hunan Prov Univ Key Lab Oncol Tradit Chinese Med, Changsha, Peoples R China.;Hunan Univ Chinese Med, Key Lab Tradit Chinese Med Mech Tumor Prevent & Tr, Changsha, Peoples R China.
摘要：
Recent research has emphasized the interaction between the circadian clock and lipid metabolism, particularly in relation to tumors. This review aims to explore how the circadian clock regulates lipid metabolism and its impact on carcinogenesis. Specifically, targeting key enzymes involved in fatty acid synthesis (SREBP, ACLY, ACC, FASN, and SCD) has been identified as a potential strategy for cancer therapy. By disrupting these enzymes, it may be possible to inhibit tumor growth by interfering with lipid metabolism. Transcription factors, like SREBP play a significant role in regulating fatty acid synthesis which is influenced by circadian clock genes such as BMAL1, REV-ERB and DEC. This suggests a strong connection between fatty acid synthesis and the circadian clock. Therefore, successful combination therapy should target fatty acid synthesis in addition to considering the timing and duration of drug use. Ultimately, personalized chronotherapy can enhance drug efficacy in cancer treatment and achieve treatment goals
作者机构：
[Yang, Kailin; Ge, Jinwen] Hunan Univ Chinese Med, Sch Integrated Chinese & Western Med, Key Lab Hunan Prov Integrated Tradit Chinese & Wes, Changsha, Peoples R China.;[Zeng, Liuting] Chinese Acad Med Sci & Peking Union Med Coll, Nanjing Drum Tower Hosp, Peking Union Med Coll, Grad Sch,Dept Rheumatol & Immunol, Nanjing, Peoples R China.;[Ge, Jinwen] Hunan Acad Chinese Med, Changsha, Hunan, Peoples R China.;[Long, Zhiyong; Zhen, Huang] Guangzhou Panyu Cent Hosp, Dept Rehabil Med, Guangzhou, Peoples R China.;[Xiao, Wei] Peoples Hosp Ningxiang City, Ningxiang, Peoples R China.
通讯机构：
[Ge, JW ] H;Hunan Univ Chinese Med, Sch Integrated Chinese & Western Med, Key Lab Hunan Prov Integrated Tradit Chinese & Wes, Changsha, Peoples R China.
关键词：
Total glucosides of paeony;Inflammatory arthritis;Rheumatoid arthritis;Ankylosing spondylitis;Osteoarthritis;Juvenile idiopathic arthritis;Psoriatic arthritis
摘要：
OBJECTIVE: To evaluate efficacy and safety of total glucosides of paeony in the treatment of 5 types of inflammatory arthritis METHODS: Databases such as Pubmed, Cochran Library, Embase were searched to collect RCTs about TGP in the treatment of inflammatory arthritis. Then, the RCTs were assessed for risk of bias and RCT data were extracted. Finally, RevMan 5.4 was used for the meta-analysis. RESULTS: A total of 63 RCTs were finally included, involving 5293 participants and 5 types of types of inflammatory arthritis: rheumatoid arthritis (RA), ankylosing spondylitis (AS), osteoarthritis (OA), juvenile idiopathic arthritis (JIA), psoriatic arthritis. For AS, TGP may improve AS disease activity score (ASDAS), decrease erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), tumor necrosis factor (TNF)- α and interleukin (IL)-6; for RA, TGP may improve disease activity of 28 joints (DAS28), decrease ESR, CRP, rheumatoid factor (RF), TNF-α and IL-6; for psoriatic arthritis, TGP may improve psoriasis area and severity index (PASI) and decrease ESR; for OA, TGP may improve visual analogue scale (VAS) and decrease nitric oxide (NO); for JIA, TGP may increase total efficiency rate, decrease ESR, CRP and TNF-α. For safety, RCTs showed that the addition of TGP did not increase adverse events, and may even reduce adverse events. CONCLUSION: TGP may improve symptoms and inflammation levels in patients with inflammatory arthritis. However, due to the low quality and small number of RCTs, large-sample, multi-center clinical trials are still needed for revision or validation.
摘要：
Cerebral ischemia-reperfusion (CIR) is a serious complication often associated with cerebral ischemia. The pur-pose of this study was to explore the therapeutic effect of nourishing qi, activating blood circulation, and inducing resuscitation (Borneol with astragaloside IV and Panax notoginseng total saponins, BAP) on CIR. Neurological function score system was used to determine the neurological function. The survival of nerve cells was detected by Nissl staining. The levels of IL-1(3, IL-18, IL-4, and IL-10 were detected by ELISA. The expression of GSDMD, GSDMD-N, Nrf2, and HO-1 proteins in hippocampus tissues was measured by immunohistochemistry (IHC). Western blot, RT-qPCR, or immunofluorescence (IF) were used to detect the NACHT, LRR, and PYD domains-containing protein 3 (NLRP3), pro-Caspase-1, Caspase-1, Nrf2, and HO-1 expression. Lactate dehy-drogenase (LDH) level was analyzed by LDH release assay. Cell viability was determined by cell counting kit-8 (CCK8). Apoptosis was detected by flow cytometry. BAP significantly promoted the recovery of nerve function, the activity of nerve cells, and the expression of Nrf2, HO-1, IL-4, and IL-10 in rat hippocampus tissues after CIR. BAP has an obvious inhibitory effect on the expression of NLRP3, pro-Caspase-1, and Caspase-1 proteins, the release of IL-1(3 and IL-18 factors, and neuronal pyroptosis in hippocampal tissues. BAP also promoted IL-4 and IL-10 levels, and the activity of SH-SY5Y cells. The IL-1(3, IL-18, NLRP3, pro-Caspase-1, Caspase-1, GSDMD, and GSDMD-N expressions were significantly inhibited by BAP in vitro, which was reversed by Nrf2 knockdown. This study confirmed that BAP alleviated rat CIR and inhibited the pyroptosis of SH-SY5Y cells by regulating the Nrf2/ HO-1 signaling pathway. This study provided new directions and ideas for the treatment of CIR.
