摘要：
It targets to explore the expression of Th17/Treg in oral submucous fibrosis (OSF) carcinogenesis and its significance in the development of mucosal lesions. In this research, 100 patients with OSF who visited our hospital for surgical treatment from March 2020 to April 2022 were selected. Based on pathological examination results, the patients were divided into 27 patients with oral leukoplakia (OK) group, 14 patients with oral lichen planus (OLP) group, 9 patients with oral squamous cell carcinoma (OSCC) group, and 50 patients with OSF group. It adopted flow cytometry (FC) to calculate the ratio of peripheral blood Th17 cells and Treg cells in four groups, and the Th17/Treg ratio was calculated; The area of oral mucosal lesions (OML) from patients was collected. It needs to compare the differences in Th17/Treg ratio and OML area among four groups and determine the correlation between indicators. ROC curve was used to analyze the diagnostic threshold of the Th17/Treg ratio for carcinogenesis. Except for the OK and OLP, it had statistical significance differences in Th17, Treg cells, and Th17/Treg ratio (P<0.001); The area of OML in the OK, OLP, and OSCC was higher than that in the simple OSF, with statistical significance (P<0.001); Th17 (%), Treg (%), and Th17/Treg all had direct ratio with the area of OML; The area of OML has directed ratio with the development of mucosal lesions (r>0, P<0.05); The areas under the ROC curve for patients with OSF combined with OK, OLP, or OSCC with Th17 (%), Treg (%), Th17/Treg, and OML area were 0.560, 0.986, 0.936, and 0.466, respectively. The expression of Th17/Treg is elevated in oral submucosal fibrosis and carcinogenesis. When mucosal lesions progress or become cancerous, the Th17/Treg ratio increases accordingly, and it has more clinical value than the increase in the OML area.
摘要：
BACKGROUND: Cerebral ischemia-reperfusion injury (CIRI), a subsequent injury caused by thrombolytic reperfusion post ischemic stroke (IS). Naotaifang (NTF) formula, a novel traditional Chinese medicine (TCM) remedy against IS, was shown to exert beneficial effects in inhibiting inflammation and inhibiting lipid peroxide synthesis in our previous research. PURPOSE: This study aimed to further explore the role of NTF in attenuating oxygen-glucose deprivation//reoxygenation (OGD/R)-induced inflammation and ferroptosis by regulating microglial M1/M2 polarization through the bone morphogenetic protein 6（BMP6）/SMADs signaling pathway. METHODS: BV2 microglia were used to establish an OGD/R model. The effects of NTF on inflammation and ferroptosis in OGD/R-injured BV2 cells were separately detected by immunofluorescence assay, fluorescent probe, DCFH-DA flow cytometry, enzyme-linked immunosorbent assay, and western-blot. RESULTS: The present results revealed that the M1 phenotype of microglia promoted the secretion of pro-inflammatory cytokines and aggravated ferroptosis and brain damage following OGD/R. However, an inhibitor of BMP6, LND-193189, reversed the aforementioned effects. Similarly, NTF promoted the shift of microglia from M1 to M2. Besides, NTF treatment effectively inhibited the expression of hepcidin, BMP6, SMADs and promoted the expression of ferroportin (FPN, SLC40A1) and γ-L-glutamyl-L-cysteinylglycine (glutathione or GSH) peroxidase 4 (GPX4). CONCLUSION: Microglial M1/M2 polarization plays a pivotal role in inflammation and ferroptosis during OGD/R. The BMP6/SMADs signaling pathway is a potential therapeutical target of inflammation and ferroptosis induced by the transformation of microglia. Moreover, NTF could alleviate inflammation and ferroptosis through the BMP6/SMADs signaling pathway in OGD/R-injured microglia.
摘要：
Cuproptosis has been reported to affect a variety of diseases. Therefore, we aimed to examine the role of cuproptosis-related genes in active ulcerative colitis (UC). We acquired 2 datasets of active UC from the Gene Expression Omnibus database and created immune cell infiltrations to research immune cell dysregulation. Based on the cuproptosis gene set and differentially expressed genes (DEGs), we identified the differentially expressed genes of cuproptosis (CuDEGs). We then used 2 machine learning methods to screen hub CuDEGs. Subsequently, we performed validation on additional datasets and investigated the relationship between hub CuDEGs and drug treatments. Thirty-five controls with inactive UC and 90 patients with active UC were obtained from the training sets. A total of 9157 DEGs and 27 CuDEGs were identified, respectively. Immune cell infiltration analysis revealed that patients with active UC exhibited higher levels of activated dendritic cells and neutrophils as well as lower levels of CD8+ T cells, regulatory T cells (Tregs), and macrophage M2. A six-gene cuproptosis signature was identified using machine learning algorithms. We further validated that the 6 hub CuDEGs showed a strong correlation with active UC and acted as cuproptosis-related biomarkers of active UC. Moreover, the expression of ATOX1 was downregulated, and SUMF1, MT1G, ATP7B, FDX1, and LIAS expression was upregulated in the colonic mucosa of active UC patients who responded to golimumab or vedolizumab therapy. With the exception of ATP7B, the expression patterns of hub CuDEGs before and after infliximab treatment of patients with active UC were similar to those of golimumab and vedolizumab. Cuproptosis and active UC have a complex relationship, as illustrated in our study. ATOX1, SUMF1, MT1G, ATP7B, FDX1, and LIAS are cuproptosis-related hub genes of active UC. Our study opens new avenues for investigating UC progression and developing novel therapeutic potential targets for the disease.
摘要：
BACKGROUNDAs an emerging potential risk factor for gastric cancer, autoimmune gastritis (AIG) has garnered increasing attention from researchers.AIMTo analyze the research overview and popular topics in the field of AIG using bibliometrics.METHODSRelevant publications on AIG in the Web of Science Core Collection were collated, and data visualization and analysis of the number of publications, countries, institutions, journals, authors, keywords, and citations were performed using software such as VOSviewer, CiteSpace, and Scimago Graphic.RESULTSIn total, 316 relevant articles were included in the analysis. From 2015 to 2022, the number of publications increased annually. The countries, institutions, authors, and journals with the highest number of publications in this field were Italy, Monash University, Toh BH, and Internal Medicine. The main keywords used in this field of research were pathogenesis, Helicobacter pylori, autoantibody, parietal cell antibody, atrophic gastritis, classification, diagnosis, autoimmune disease, risk, cancer, gastric cancer, vitamin B12 deficiency, and pernicious anemia. The following directions may be popular for future research: (1) The role of Helicobacter pylori in the pathogenesis of AIG; (2) diagnostic criteria for AIG and reference values for serum antibodies; (3) comorbidity mechanisms between AIG and other autoimmune diseases; (4) specific risks of AIG complicating gastric and other cancers; and (5) the role of vitamin B12 supplementation in patients with early-stage AIG.CONCLUSIONThis bibliometric analysis reported on popular topics and emerging trends in AIG, with diagnosis and prognosis being research hotspots in this field.
期刊：
JOURNAL OF BIOLOGICAL REGULATORS AND HOMEOSTATIC AGENTS,2023年37(3):1381-1391 ISSN：0393-974X
通讯作者：
Chen, XY;Cai, HZ
作者机构：
[Deng, Xu; Chen, Xinyu; Xu, Zelin] Hunan Univ Tradit Chinese Med, Hosp 1, Dept Prevent & Treatment Ctr, Changsha 410007, Hunan, Peoples R China.;[Luo, Yuntao] Hunan Univ Tradit Chinese Med, Hosp 1, Dept Hlth Management, Changsha 410007, Hunan, Peoples R China.;[Cai, Huzhi] Hunan Univ Tradit Chinese Med, Hosp 1, Dept Int Med, Changsha 410007, Hunan, Peoples R China.
通讯机构：
[Chen, XY ; Cai, HZ ] H;Hunan Univ Tradit Chinese Med, Hosp 1, Dept Prevent & Treatment Ctr, Changsha 410007, Hunan, Peoples R China.;Hunan Univ Tradit Chinese Med, Hosp 1, Dept Int Med, Changsha 410007, Hunan, Peoples R China.
关键词：
Notch signal pathway;miR-18a-5p;chronic heart failure;cardiac function;cardiomyocyte;apoptosis
摘要：
Objectives: To explore how the mechanism of miR-18a-5p overexpression through the Notch signaling pathway improves cardiac function and inhibits cardiomyocyte apoptosis in chronic heart failure rats. Methods: Forty rats were randomly divided into contrast group, negative control (NC) group, high-expression group, and low -expression group by random number table, with ten rats in each group. NC group rats, high-expression group rats, and low -expression group rats were injected intraperitoneally with 2 mg/mL adriamycin solution to establish the rat model of chronic heart failure. The miR-18a-5p overexpression and inhibition lentivirus vector was constructed, and the miR-18a-5p overexpression and inhibition lentivirus suspension were injected into the myocardium of rats in the high-expression group and low-expression group respectively. No treatment was made in the contrast group and NC group. The expression levels of miR-18a-5p were detected in the myocardial tissue of rats and the cardiac function of rats. In addition, the apoptosis of rat cardiomyocytes was observed, and the expression levels of apoptosis-related proteins (Cleaved-caspase-3, Bax, and Bcl-2) were detected in the myocardial tissue of rats. The possible binding sites of miR-18a-5p and Notch2 3 ' untranslated region (UTR) region were predicted, and the interaction between miR-18a-5p and Notch2 was verified. Finally, the expression levels of Notch signal pathway-related genes and proteins (Notch2, Hes1, and Hes5) were detected in the myocardial tissue of rats. Results: In comparison with the NC group, miR-18a-5p expression levels in myocardial tissue of high-expression group rats increased (p < 0.05), and that of low-expression group rats decreased (p < 0.05). In contrast with the NC group and low-expression group, the values of left ventricular end-diastolic dimension (LVEDD) and left ventricular end-systolic dimension (LVESD) in the high-expression group decreased (p < 0.05), and the values of left ventricular ejection fraction (LVEF) and fraction shortening (FS) of the left ventricle in the high-expression group increased (p < 0.05). In comparison with the NC group and low-expression group, myocardial cell apoptosis in the high-expression group decreased (p < 0.05), and the protein expression levels of Cleaved-caspase-3 and Bax in myocardial tissue of high-expression group rats decreased (p < 0.05). Moreover, the Bcl-2 protein expression levels in the myocardial tissue of high-expression group rats increased (p < 0.05). Through prediction and verification, miR-18a-5p might bind to the "GCACCUUA" site of the Notch2 3 ' UTR region, which could inhibit the activity of wild-type Notch2 3 ' UTR luciferase reporter plasmid but could not inhibit the activity of mutant Notch2 3 ' UTR luciferase reporter plasmid. In comparison with the NC group and low-expression group, the messenger ribonucleic acid (mRNA) and protein expression levels of Notch signal pathway-related factors Notch2, Hes1, and Hes5 in myocardial tissue of high-expression group rats were decreased (p < 0.05).Conclusions: miR-18a-5p overexpression could improve cardiac function and inhibit cardiomyocyte apoptosis in chronic heart failure rats, which might be related to the regulation of the Notch signal pathway.
摘要：
Acute-on-chronic liver failure (ACLF) is a progressive disease that is associated with rapid worsening of clinical symptoms and high mortality. A multicentre prospective study from China demonstrated that patients with hepatitis B virus-related ACLF (HBV-ACLF) exhibited worse clinical characteristics and higher mortality rates compared to non-HBV-ACLF patients. Immune dysregulation is closely linked to the potential mechanisms of initiation and progression of ACLF. Innate immune response, which is represented by monocytes/macrophages, is up-regulated across ACLF development. This suggests that monocytes/macrophages play an essential role in maintaining the immune homeostasis of ACLF. Information that has been published in recent years shows that the immune status and function of monocytes/macrophages vary in ACLF precipitated by different chronic liver diseases. Monocytes/macrophages have an immune activation effect in hepatitis B-precipitated-ACLF, but they exhibit an immune suppression in cirrhosis-precipitated-ACLF. Therefore, this review aims to explain whether this difference affects the clinical outcome in HBV-ACLF patients as well as the mechanisms involved. We summarize the novel findings that highlight the dynamic polarization phenotype and functional status of hepatic macrophages from the stage of HBV infection to ACLF development. Moreover, we discuss how different HBV-related liver disease tissue microenvironments affect the phenotype and function of hepatic macrophages. In summary, increasing developments in understanding the differences in immune phenotype and functional status of hepatic macrophages in ACLF patients will provide new perspectives towards the effective restoration of ACLF immune homeostasis.
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：
Improving hepatic glucose and lipid metabolisms is an important strategy to treat type 2 diabetes mellitus complicated with non-alcoholic fatty liver disease (T2DM-NAFLD). Silybin (SLB) has the potential hepatoprotection, while its oral bioavailability is poor. This study aims to investigate the functional role and mechanism of liposomal SLB in modulating glucose/lipid metabolism in T2DM-NAFLD. SLB was prepared by thin film dispersion method and characterized using dynamic light scattering, scanning electron microscope, high performance liquid chromatography and zeta potential analyzer. A rat model of T2DM-NAFLD was used to determine the role of liposomal SLB in regulating glycolipid metabolism and hepatic damage. Rat primary hepatocytes were used to demonstrate the hepatoprotection mechanism of liposomal SLB. The encapsulation efficiency was more than 80%, which showed the average particle size of 119.76 nm. Also, the average Zeta potential was -4.76 mV. These liposomes were spherical. In rats with T2DM-NAFLD, liposomal SLB alleviated insulin resistance and lipid metabolism, thereby improving hepatic lipid accumulation, inflammation and fibrosis. Besides, liposomal SLB elevated AMPK phosphorylation, and decreased collagen I/III, α-smooth muscle actin (α-SMA), transforming growth factor-β1 (TGF-β1) and the phosphorylation of Smad2/3. In hepatocyte model, compound C partially reversed the effects of liposomal SLB on cell viability, glycolipid metabolism and AMPK/TGF-β1/Smad pathway activation. Liposomal SLB ameliorates hepatic glucose and lipid metabolisms in T2DM-NAFLD via activating AMPK/TGF-β1/Smad pathway, providing an efficient strategy for treating T2DM-NAFLD.
摘要：
Liuwei Dihuang Pill (LP) was verified to alleviate postmenopausal osteoporosis (PMOP) development. Nevertheless, the major constituent of LP and the related network pharmacology study remain unexplored. Protein–protein interaction was established to identify the downstream target of LP in PMOP, and the related signaling pathway was investigated by bioinformatics analysis. MC3T3-E1 cells were added to ferric ammonium citrate (FAC) to mimic osteoporosis in vitro. The osteoblasts were identified by Alizarin red staining. Western blot was applied to evaluate protein levels. In addition, Cell Counting Kit-8 (CCK8) assay was applied to assess cell viability, and cell apoptosis was assessed by flow cytometry. Quercetin was the major constituent of LP. In addition, quercetin significantly reversed FAC-induced inhibition of osteogenic differentiation in MC3T3-E1 cells. In addition, quercetin notably abolished the FAC-induced upregulation of Bax, Caspase-3, FOS, JUN, TGFB1 and PPARD. In contrast, Bcl-2, p-mTOR/mTOR, p-AKT/AKT and p-PI3K/PI3K levels in MC3T3-E1 cells were reduced by FAC, which was restored by quercetin. Meanwhile, FAC notably inhibited the viability of MC3T3-E1 cells via inducing apoptosis, but this impact was abolished by quercetin. Furthermore, quercetin could reverse pcDNA3.1-FOS-mediated growth of FAC-treated osteoblasts by mediating PI3K/AKT/mTOR signaling. Quercetin alleviated the progression of PMOP via activation of PI3K/AKT/mTOR signaling. Hence, this study would shed novel insights into discovering new methods against PMOP.
期刊：
Frontiers in Microbiology,2023年14:1288430 ISSN：1664-302X
通讯作者：
Jiang, Ping;Tan, ZJ;Jiang, P
作者机构：
[Tan, Zhoujin; Liu, Jing; Wu, Yi; Jiang, Ping; Deng, Na] Hunan Univ Chinese Med, Coll Tradit Chinese Med, Changsha, Peoples R China.;[Jiang, Ping] Hunan Univ Chinese Med, Affiliated Hosp 1, Changsha, Peoples R China.
通讯机构：
[Jiang, P; Tan, ZJ ; Jiang, P ] H;Hunan Univ Chinese Med, Coll Tradit Chinese Med, Changsha, Peoples R China.;Hunan Univ Chinese Med, Affiliated Hosp 1, Changsha, Peoples R China.
关键词：
Chinese medicine;cold-dampness trapped spleen syndrome;diarrhea;digestive enzyme activities;intestinal microbiota
摘要：
INTRODUCTION: Cold and humid environments alter the intestinal microbiota, and the role of the intestinal microbiota in the development of diarrhea associated with cold-dampness trapped spleen syndrome in Chinese medicine is unclear. METHODS: The 30 mice were randomly divided into normal and model groups, with the model group being exposed to cold and humid environmental stresses for 7 days. Then, mouse intestinal contents were collected and analyzed their intestinal microbiota and digestive enzymes. RESULTS: Our findings revealed significant increases in sucrase and lactase activities, as well as microbial activity, in the model group (p < 0.05). β-diversity analysis highlighted distinct intestinal microbiota compositions between the two groups. Specifically, the experimental group showed a unique dominance of the genera and strains Clostridium sensu stricto 1 and Clostridium sp. ND2. LEfSe analysis identified Helicobacter, Roseburia, and Eubacterium plexicaudatum ASF492 as differentially abundant species in them model group. Network analysis demonstrated that rare bacterial species mostly governed the microbial interactions, exhibiting increased mutual promotion. On the other hand, abundant species like Lactobacillus johnsonii and Lactobacillus reuteri showed mutual inhibitory relationships. DISCUSSION: In summary, exposure to cold and humid conditions led to increased intestinal enzyme activities and a shift in microbial composition, favoring the growth of rare bacterial species. These changes suggest that rare bacteria in the intestinal microbiota play a critical role in the pathology of diarrhea associated with cold-dampness trapped spleen syndrome, revealing unique survival strategies among bacterial populations under stressful conditions.
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.
期刊：
Ageing Research Reviews,2023年91:102063 ISSN：1568-1637
通讯作者：
Yang, Kailin;Ge, JW;Zeng, LT
作者机构：
[Wang, Shanshan; He, Qi; 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.;[Yang, Kailin; Ge, Jinwen] Hunan Acad Chinese Med, Changsha, Hunan, Peoples R China.;[Zeng, Liuting; Zeng, LT] Chinese Acad Med Sci & Peking Union Med Coll, Nanjing Drum Tower Hosp, Grad Sch, Peking Union Med Coll,Dept Rheumatol & Immunol, Nanjing, Peoples R China.;[Zeng, Jinsong; Ge, Anqi] Hunan Univ Chinese Med, Hosp 1, Changsha, Hunan, Peoples R China.;[He, Qi; Deng, Ying] Peoples Hosp Ningxiang City, Ningxiang, Peoples R China.
通讯机构：
[Zeng, LT ] C;[Yang, KL; Ge, JW ] H;Hunan Univ Chinese Med, Sch Integrated Chinese & Western Med, Key Lab Hunan Prov Integrated Tradit Chinese & Wes, Changsha, Peoples R China.;Chinese Acad Med Sci & Peking Union Med Coll, Nanjing Drum Tower Hosp, Grad Sch, Peking Union Med Coll,Dept Rheumatol & Immunol, Nanjing, Peoples R China.
摘要：
Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder of the central nervous system after Alzheimer's disease. The current understanding of PD focuses mainly on the loss of dopamine neurons in the substantia nigra region of the midbrain, which is attributed to factors such as oxidative stress, alpha-synuclein aggregation, neuroinflammation, and mitochondrial dysfunction. These factors together contribute to the PD phenotype. Recent studies on PD pathology have introduced a new form of cell death known as ferroptosis. Pathological changes closely linked with ferroptosis have been seen in the brain tissues of PD patients, including alterations in iron metabolism, lipid peroxidation, and increased levels of reactive oxygen species. Preclinical research has demonstrated the neuroprotective qualities of certain iron chelators, antioxidants, Fer-1, and conditioners in Parkinson's disease. Natural plant products have shown significant potential in balancing ferroptosis-related factors and adjusting their expression levels. Therefore, it is vital to understand the mechanisms by which natural plant products inhibit ferroptosis and relieve PD symptoms. This review provides a comprehensive look at ferroptosis, its role in PD pathology, and the mechanisms underlying the therapeutic effects of natural plant products focused on ferroptosis. The insights from this review can serve as useful references for future research on novel ferroptosis inhibitors and lead compounds for PD treatment.
摘要：
Glaucoma, one of the most common ocular neurodegenerative diseases worldwide, is characterized by retinal ganglion cell (RGC) loss. There is a large body of literature that describes the neuroprotective role of melatonin against neurodegenerative diseases by regulating neuroinflammation, although the exact mechanism through which melatonin acts on RGC is still uncertain. This study assessed the protective effects of melatonin using a NMDA-induced RGC injury model, and studied the possible mechanisms involved in this process. Melatonin promoted RGC survival, improved retinal function, and inhibited the apoptosis and necrosis of retinal cells. To understand the mechanism of the neuroprotective effects of melatonin on RGC, microglia and inflammation -related pathways were assessed after melatonin administration and microglia ablation. Melatonin promoted RGC survival by suppressing microglia-derived proinflammatory cytokines, in particular TNF alpha, which in turn inhibited the activation of p38 MAPK pathway. Inhibiting TNF alpha or manipulating p38 MAPK pathway protected damaged RGC. Our results suggest that melatonin protects against NMDA-induced RGC injury by inhibiting the microglial TNF alpha-RGC p38 MAPK pathway. It should be considered a candidate neuroprotective therapy against retinal neurodegenerative diseases.
期刊：
International Journal of Colorectal Disease,2023年38(1):1-16 ISSN：0179-1958
通讯作者：
Xu, Yin;Zhu, Y
作者机构：
[Zhu, Ying; Zhou, Tao; Xu, Yin; Liu, Yaxuan; Zhu, Y; Long, Dan] Hunan Univ Chinese Med, Hosp 1, Changsha, Hunan, Peoples R China.;[Mao, Chenhan] Nanjing Univ Chinese Med, Affiliated Hosp Integrated Tradit Chinese & Wester, Nanjing, Jiangsu, Peoples R China.
通讯机构：
[Xu, Y; Zhu, Y ] H;Hunan Univ Chinese Med, Hosp 1, Changsha, Hunan, Peoples R China.
关键词：
Intestinal obstruction (IO);Global burden;Disability-adjusted life years (DALY);Joinpoint regression analysis;Age-period-cohort analysis
摘要：
BACKGROUND: Intestinal obstruction (IO) is a common surgical acute abdominal condition that places a significant burden on modern health systems. Unfortunately, the global burden and trends of IO remain unknown. Therefore, this study aimed to comprehensively assess its long-term trends and epidemiological features, which will help policymakers to formulate appropriate health policies. METHODS: We conducted an ecological study using data from the Global Burden of Disease Study (GBD) 2019. Data on IO were analyzed by sex, age, year, sociodemographic index (SDI), and location according to GBD 2019. In addition, joinpoint regression analysis was used to assess temporal trends. Age-period-cohort analysis (APC Analysis) was conducted to evaluate age, period, and birth cohort effects on IO incidence and mortality risk. RESULTS: Globally, the prevalent and incident cases increased by 56.91% and 86.67% from 1990 to 2019, respectively. Joinpoint regression analysis showed that age-standardized incidence rate (ASIR) and age-standardized prevalence rate (ASPR) increased, but age-standardized mortality rate (ASMR) and age-standardized disability-adjusted life year (DALY) rate decreased over the past three decades. The age effect demonstrated that older people have ahigher risk of morbidity and mortality. The period effect of incidence and mortality showed an upward trend from 1990 to 2019. Cohort effect revealed that the incidence and death risk peaked in the earlier-born cohort and was lower in the more recent-born cohort. Notably, we found that the burden of IO was higher in males than in females throughout the study period. There are huge disparities in IO burden among countries. CONCLUSION: Globally, the reported incidence and prevalence of IO increased from 1990 to 2019. The burden of IO differed markedly by age, sex, country, and region. Middle-aged and elderly people over 50 years old were at high risk. Given the ageing population, the burden of IO will be a major public health challenge. Thus, there is a strong necessity to strengthen prevention and early intervention in the at-risk population.
摘要：
Oncogenic super-enhancers (SEs) generate noncoding enhancer/SE RNAs (eRNAs/seRNAs) that exert a critical function in malignancy through powerful regulation of target gene expression. Herein, we show that a JUN-mediated seRNA can form R-loop to regulate target genes to promote metastasis of nasopharyngeal carcinoma (NPC). A combination of global run-on sequencing, chromatin-immunoprecipitation sequencing, and RNA sequencing was used to screen seRNAs. A specific seRNA associated with NPC metastasis (seRNA-NPCM) was identified as a transcriptional regulator for N-myc downstream-regulated gene 1 (NDRG1). JUN was found to regulate seRNA-NPCM through motif binding. seRNA-NPCM was elevated in NPC cancer tissues and highly metastatic cell lines, and promoted the metastasis of NPC cells in vitro and in vivo. Mechanistically, the 3' end of seRNA-NPCM hybridizes with the SE region to form an R-loop, and the middle segment of seRNA-NPCM binds to heterogeneous nuclear ribonucleoprotein R (hnRNPR) at the promoter of distal gene NDRG1 and neighboring gene tribbles pseudokinase 1 (TRIB1). These structures promote chromatin looping and long-distance chromatin interactions between SEs and promoters, thus facilitating NDRG1 and TRIB1 transcription. Furthermore, the clinical analyses showed that seRNA-NPCM and NDRG1 were independent prognostic factors for NPC patients. seRNA-NPCM plays a critical role in orchestrating target gene transcription to promote NPC metastasis.
期刊：
WORLD JOURNAL OF BIOLOGICAL PSYCHIATRY,2023年24(2):149-161 ISSN：1562-2975
通讯作者：
Deming Wang<&wdkj&>Ji Xiao
作者机构：
[Huang, Zixia; Wang, Deming; Xiao, Ji; Fan, Xuhong; Wu, Mingyue] Univ South China, Affiliated Hosp 2, Dept Anesthesiol, Hengyang, Peoples R China.;[Zhao, Zhenyu] Hunan Univ Chinese Med, Hosp 1, Dept Anesthesiol, Changsha, Peoples R China.
通讯机构：
[Deming Wang; Ji Xiao] D;Department of Anesthesiology, The Second Affiliated Hospital of University of South China, Hengyang, China<&wdkj&>Department of Anesthesiology, The Second Affiliated Hospital of University of South China, Hengyang, China
期刊：
Molecular and Cellular Biochemistry,2023年478(8):1791-1802 ISSN：0300-8177
通讯作者：
Qinghu He
作者机构：
[Luo, Min; Chen, Jisong; Hu, Zongren; He, Qinghu] Hunan Univ Med, Dept Rehabil & Healthcare, 492 Jinxi South Rd, Huaihua City, Hunan, Peoples R China.;[Wang, Neng; Hu, Zongren; He, Qinghu] Hunan Univ Chinese Med, Sch Integrated Chinese & Western Med, Changsha 410208, Hunan, Peoples R China.;[Zhang, Yuanting] Hunan Univ Chinese Med, Affiliated Hosp 1, Changsha 410007, Hunan, Peoples R China.;[Luo, Min] Cent South Univ, Xiangya Hosp 2, Changsha 410011, Hunan, Peoples R China.;[Xiao, Yinfu] Hunan Univ Chinese Med, Sch Tradit Chinese Med, Changsha 410208, Hunan, Peoples R China.
通讯机构：
[Qinghu He] D;Department of Rehabilitation and Healthcare, Hunan University of Medicine, Huaihua City, China<&wdkj&>School of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, China
摘要：
Erectile dysfunction (ED) is a major health problem affecting a large proportion of the general population. Testosterone also plays a key role in sexual dysfunction. In this study, we found that testosterone can inhibit cavernous fibrosis by affecting the expression of miR-22-3p, providing a new basis for research and treatment of ED. Old and young rats were used to study the effects of testosterone on cavernous fibrosis. Hematoxylin and eosin (HE) and Masson's staining were used to observe the cavernous tissue. A luciferase assay was used to analyze the relationship between the miR-22-3p, TGF beta R1, and Galectin-1 signaling pathways. CCK-8 and flow cytometry were used to detect the proliferation and apoptosis rates of cavernosum smooth muscle cells (CSMCs) following testosterone intervention. Immunohistochemical analysis was performed to examine the positive rate of caspase 3 and Ki67. IF was used to analyze the expression of collagen IV, MMP2, and alpha-SMA. The levels of GnRH, tT, LH, and F-TESTO in old rats increased after testosterone intervention. miR-22-3p inhibits the expression of TGF beta R1 and Galectin-1. The protein expression of TGF beta R1, Galectin-1, SMAD2, and p-SMAD2 was reduced by testosterone. The expression levels of alpha-SMA, collagen I, collagen IV, FN, and MMP2 in the cavernous tissues of old rats treated with testosterone were significantly reduced. The levels of caspase 3 and collagen IV decreased, and the levels of MMP2, Ki67, and alpha-SMA increased. Testosterone and miR-22-3p inhibit CSMC apoptosis and promote cell proliferation. Testosterone promoted the expression of miR-22-3p to interfere with the expression of the cavernous TGF beta R1 and Galectin-1 signaling pathways. Testosterone can reduce cavernous fibrosis during the treatment of functional ED.
期刊：
Cell Biochemistry and Function,2023年41(7):857-867 ISSN：0263-6484
通讯作者：
Tang, CG;Wang, MQ
作者机构：
[Tang, Chenguang; Luo, Jing] Shenzhen Qianhai Shekou Free Trade Zone Hosp, Dept Tradit Chinese Med, Shenzhen, Peoples R China.;[Deng, Yijue; Wang, MQ; Wang, Mengqing; Luo, Jing] Hunan Univ Chinese Med, Hosp 1, Dept Paediat, Changsha, Peoples R China.;[Ding, Yi] Changsha Social Work Coll, Sch Rehabil, Changsha, Peoples R China.
通讯机构：
[Tang, CG ] S;[Wang, MQ ] H;Shenzhen Qianhai Shekou Free Trade Zone Hosp, Dept Tradit Chinese Med, Shenzhen, Peoples R China.;Hunan Univ Chinese Med, Hosp 1, Dept Paediat, Changsha, Peoples R China.
关键词：
EKR signaling;Xie Bai Zeng Ye decoction;cytokine;montelukast sodium;postinfectious cough;respiratory function
摘要：
This study aimed to determine the effects of Xiebai Zengye decoction (XBZY)on airway inflammation and respiratory function in rats with postinfectious cough (PIC),and its regulatory effects on the extracellular signal-regulated kinase (ERK)signaling pathway. Compared with the normal group, the rats from thePIC group had significantly shortened expiratory time (TE)and enhanced pause (EEP),increased resistance (RT),and enhanced pause (Penh), along with increased levels of serum interleukin-4 (IL-4)and IL-6,and decreased levels of IL-10. The lung and colon tissues of rats from the PIC group showed histopathological changes, including inflammatory cell infiltration, damaged mucosal epithelium, and crypt structure, with significantly increased ERK mRNA and protein expression levels. Treatment with XBZY and montelukast sodium (MAS)improved the respiratory function and serum cytokine levels, reduced tissue inflammation, and decreased ERK mRNA and protein expression levels in the lung and colon tissues. In the lung tissues, XBZY treatment significantly decreased the expression of phosphorylated-ERK (p-ERK)protein, as well as p-MEK1/2, p-ERK1/2, and p-c-Fos proteins, while in the colon tissues, XBZY significantly decreased the expression of p-ERK1/2and p-c-Fos proteins. However, MAS treatment only showed significant improvement in the lung tissue inflammation score, and the expression level of p-ERK protein in the lung tissue was decreased. In conclusion, the present study suggests that XBZY has a potential therapeutic effect on PIC by improving respiratory function and attenuating inflammation, and this effect may be associated with the inhibition of the ERK signaling pathway. These findings could provide a new direction for the development of treatments for PIC. However, further research is needed to elucidate the underlying molecular mechanisms of XBZY and to confirm its safety and efficacy in clinical trials.
摘要：
Diabetic retinopathy (DR) is a common cause of visual impairment. Apigenin has been shown to have antiangiogenic effects in various diseases. Our study aimed to investigate the role of apigenin in DR and elucidate the underlying mechanism. Human retinal microvascular endothelial cells (HRMECs) were exposed to high glucose (HG) to establish a DR model. HRMECs were treated with apigenin. Then we knocked down or overexpressed miR-140-5p and HDAC3, and added PI3K/AKT inhibitor LY294002. The expression levels of miR-140-5p, HDAC3, and PTEN were measured using qRT-PCR. Western blot analysis was performed to assess the expression of HDAC3, PTEN, and PI3K/AKT pathway-related proteins. Finally, cell proliferation and migration were evaluated using MTT, wound-healing assay, and transwell assay, while angiogenesis was examined using the tube formation assay. HG treatment resulted in reduced miR-140-5p expression and overexpression of miR-140-5p suppressed proliferation, migration, and angiogenesis of the HG-induced HRMECs. Apigenin treatment significantly restored the decreased level of miR-140-5p caused by HG treatment and inhibited proliferation, migration, and angiogenesis of the HG-induced HRMECs by upregulating miR-140-5p. Moreover, miR-140-5p targeted HDAC3, and overexpression of miR-140-5p reversed the HG-inducted upregulation of HDAC3 expression. HDAC3 was found to bind to the promoter region of PTEN, inhibiting its expression. Knockdown of HDAC3 suppressed the PI3K/AKT pathway by elevating PTEN expression. Furthermore, apigenin inhibited angiogenesis in DR cell models through the regulating of the miR-140-5p/HDAC3-mediated PTEN/PI3K/AKT pathway. Apigenin effectively suppressed angiogenesis in HG-induced HRMECs by modulating the miR-140-5p/HDAC3-mediated PTEN/PI3K/AKT pathway. Our study may contribute to the development of novel therapeutic approaches and identification of potential targets for the treatment of DR. 1. Overexpression of miR-140-5p suppressed proliferation, migration, and angiogenesis of HG-induced HRMECs. 2. Apigenin suppressed HG-induced HRMECs proliferation, migration, and angiogenesis by increased the expression of miR-140-5p. 3. miR-140-5p targeted HDAC3. 4. Knockdown HDAC3 repressed PI3K/AKT pathway via elevating PTEN expression. 5. In a diabetic retinopathy (DR) cell model, apigenin can inhibit angiogenesis by regulating the miR-140-5p/HDAC3-mediated PTEN/PI3K/AKT pathway.
