摘要:
OBJECTIVES: Statistics on the rate of unconventional lymph node metastases (ULNM) at the time of one-stage radical surgery in tongue cancer patients. To assess whether an extended neck dissection group with additional removal of ULNs has a lower rate of neck recurrence compared to the traditional neck dissection group. MATERIALS AND METHODS: A total of 336 patients with TSCC who underwent radical surgery were recruited and underwent traditional or extended neck dissection. Compared to traditional neck dissection, the aim of extended neck dissection is designed to additional resect ULNs. RESULTS: In total, 180 patients underwent extended neck dissection, while 156 underwent traditional neck dissection. The incidence of ULNM was 11.67% (21/180) in patients treated with extended neck dissection. The incidence of ipsilateral neck recurrence was 9.49% and 0.56% in patients who underwent traditional and extended neck dissection, respectively (p = 0.0001). CONCLUSIONS: Extended neck dissection is effective for preventing neck recurrence in TSCC patients with ULNs. CLINICAL RELEVANCE: ULNM may be the main cause of neck recurrence after neck dissection in patients with tongue cancer. A better prognosis may be achieved by additional resection of ULNs on the basis of traditional neck dissection.
期刊:
Frontiers in Bioscience-Landmark,2023年28(10):271 ISSN:2768-6701
通讯作者:
Yu, Lili;Wu, QB;Fan, XM
作者机构:
[Luo, Dan; Wang, Jue; Liang, Yuling; Yu, Lili; Wu, Qibiao] Macau Univ Sci & Technol, State Key Lab Qual Res Chinese Med, Fac Chinese Med, Taipa 999078, Macao, Peoples R China.;[Luo, Dan; Fan, Xianming; Wang, Wenjun; Gui, Xuemei; Yan, Jie; Fang, Mengying; Liang, Yuling; Chen, Mengqin] Southwest Med Univ, Affiliated Hosp, Dept Resp & Crit Care Med, Luzhou 646099, Sichuan, Peoples R China.;[Luo, Dan; Fan, Xianming; Wang, Wenjun; Gui, Xuemei; Yan, Jie; Fang, Mengying; Liang, Yuling; Chen, Mengqin] Southwest Med Univ, Affiliated Hosp, Inflammat & Allerg Dis Res Unit, Luzhou 646099, Sichuan, Peoples R China.;[Shao, Le] Hunan Univ Chinese Med, Hosp 1, Ctr Med Res & Innovat, Changsha 410021, Hunan, Peoples R China.;[Wu, Qibiao] Guangdong Univ Technol, Guangdong Hong Kong Macao Joint Lab Contaminants, Guangzhou 510520, Peoples R China.
通讯机构:
[Yu, LL; Wu, QB ] M;[Fan, XM ] S;Macau Univ Sci & Technol, State Key Lab Qual Res Chinese Med, Fac Chinese Med, Taipa 999078, Macao, Peoples R China.;Southwest Med Univ, Affiliated Hosp, Dept Resp & Crit Care Med, Luzhou 646099, Sichuan, Peoples R China.;Southwest Med Univ, Affiliated Hosp, Inflammat & Allerg Dis Res Unit, Luzhou 646099, Sichuan, Peoples R China.
摘要:
BACKGROUND: Lung cancer is the main cause of cancer-related death, with epithelial-mesenchymal transition (EMT) playing an important role in the development of this disease. The EMT-related genes Polypeptide N-Acetylgalactosaminyltransferase 3 (GALNT3) and 2'-5'-Oligoadenylate Synthetase 1 (OAS1) are involved in numerous tumor processes. Although these genes have been extensively studied in cancer, they have yet to be analyzed by multi-omics in lung adenocarcinoma (LUAD). METHODS: EMT-related genes were identified by R and Venn diagram. Cox regression and Kaplan-Meier analysis were performed to evaluate patient survival, and the Gene Expression Profiling Interactive Analysis (GEPIA) database was used for correlation analysis. GeneCards and R packages were used to explore gene characterization and functional annotation. The Tumor Immune Estimation Resource (TIMER), Human Protein Atlas (HPA), University of Alabama at Birmingham Cancer (UALCAN), and The Cancer Genome Atlas (TCGA) databases were used to investigate gene expression, which was then confirmed by RT-PCR. Clinicopathological analysis was carried out using the UALCAN database. Functional mechanisms and multi-omics analysis were performed using DNA Methylation Interactive Visualization Database (DNMIVD), Targetscan, TIMER, Tumor-immune System Interactions Database (TISIDB) and cBioportal. Diagnostic values were calculated using ROC curve analysis. RESULTS: A total of 320 EMT-related genes were identified in LUAD. Their characteristics were confirmed in the Database for Annotation, Visualization and Integrated Discovery (DAVID) database by the intersection of 855 and 3600 different genes from the Gene Expression Omnibus (GEO) and EMTome databases, respectively. Expression of the EMT-related genes GALNT3 and OAS1 was associated with the prognosis of LUAD patients. A positive correlation was observed between the expression of GALNT3 and OAS1, and their expression was higher in LUAD tissue than in normal lung tissue. This was confirmed using RT-PCR. Multi-omics analysis revealed that GALNT3 and OAS1 expression was associated with gene mutation and methylation, cellular immune infiltration, and several immune subtypes. A miRNA-GALNT3/OAS1 regulatory network was also found. Receiver operating characteristic (ROC) curve analysis found that GALNT3 and OAS1 expression combined had superior diagnostic value to that of each marker alone. CONCLUSIONS: GALNT3 and OAS1 expression are associated with immune cell infiltration and poor prognosis in LUAD. Their combined expression has high diagnostic value; hence, GALNT3 and OAS1 may be valuable biomarkers for the early detection of LUAD.
作者机构:
[Zhang, Weili; Jin-si-han, E-er-man-bie-ke; Lu, ZH; Lian, Shaopu; Li, Yuan; Lu, Zhenhai; Feng, Cheng; Wang, Hao] Sun Yat Sen Univ Canc Ctr, Dept Colorectal Surg, Guangzhou 510515, Guangdong, Peoples R China.;[He, Meng; He, M] Chinese Acad Med Sci & Peking Union Med Coll, Natl Clin Res Ctr Canc, Canc Hosp, Dept Radiat Oncol,Natl Canc Ctr, Shenzhen 518116, Guangdong, Peoples R China.;[He, Meng; He, M] Chinese Acad Med Sci & Peking Union Med Coll, Shenzhen Hosp, Shenzhen 518116, Guangdong, Peoples R China.;[Chen, QF; Chen, Qifeng] Sun Yat Sen Univ Canc Ctr, Dept Minimally Invas Intervent Therapy, Liver Canc Study & Serv Grp, Guangzhou 510060, Guangdong, Peoples R China.;[Tai, Yi] Sun Yat Senen Univ Canc Ctr, Dept Musculoskeletal Oncol, Guangzhou 510515, Guangdong, Peoples R China.
通讯机构:
[Chen, QF ; Lu, ZH ] S;[He, M ] C;Sun Yat Sen Univ Canc Ctr, Dept Colorectal Surg, Guangzhou 510515, Guangdong, Peoples R China.;Chinese Acad Med Sci & Peking Union Med Coll, Natl Clin Res Ctr Canc, Canc Hosp, Dept Radiat Oncol,Natl Canc Ctr, Shenzhen 518116, Guangdong, Peoples R China.;Chinese Acad Med Sci & Peking Union Med Coll, Shenzhen Hosp, Shenzhen 518116, Guangdong, Peoples R China.
摘要:
Neutrophil extracellular traps (NETs) have been categorized as a form of inflammatory cell death mode of neutrophils (NETosis) involved in natural immunity and the regulation of adaptive immunity. More and more studies revealed the ability of NETs to reshape the tumor immune microenvironment (TIME) by limiting antitumor effector cells, which may impair the efficacy of immunotherapy. To explore whether NETs-related genes make vital impacts on Colon carcinoma (COAD), we have carried out a systematic analysis and showed several findings in the present work. First, we obtained the patient's data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) dataset, aiming to detect two NETs-associated subtypes by consensus clustering. For the purpose of annotating the roles of NETs-related pathways, gene ontology enrichment analyses were adopted. Next, we constructed a 6 novel NETs-related genes score using the Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression model. We found that the NETs risk score was notably upregulated in COAD patient samples, and its levels were notably correlated with tumor clinicopathological and immune traits. Then, according to NETs-associated molecular subtypes and the risk signature, this study compared immune cell infiltration calculated through the estimate, CIBERSORT, TIMER, ssGSEA algorithms, tumor immune dysfunction, as well as exclusion (TIDE). Furthermore, we confirm that MPO(myeloperoxidase) was significantly upregulated in COAD patient samples, and its levels were significantly linked to tumor malignancy and clinic outcome. Moreover, multiplex immunohistochemistry (mIHC) spatial analysis confirmed that MPO was closely related to Treg and PD-1 + Treg in spatial location which suggested MPO may paly an important role in TIME formation. Altogether, the obtained results indicated that a six NETs-related genes prognostic signature was conducive to estimating the prognosis and response of chemo-/immuno-therapy of COAD patients.
期刊:
Journal of Nanobiotechnology,2023年21(1):1-21 ISSN:1477-3155
通讯作者:
Long, Y;Liu, B
作者机构:
[Qin, Zhang; Zhang, Yi; Li, Zhenxian; Peng, Yuan; Xu, Yijia; Long, Yun; Liu, Jianhe; Jiang, Jiazheng] Hunan Univ Chinese Med, Hosp 1, Branch Natl Clin Res Ctr Chinese Med Cardiol, Dept Cardiol, Changsha 410007, Peoples R China.;[Liu, B; Liu, Bin] Hunan Univ, Coll Biol, Changsha 410082, Peoples R China.;[Liu, Hao] Cent South Univ, Xiangya Hosp 2, Dept Rehabil, Changsha 410011, Peoples R China.;[Liu, B; Liu, Dayue; Liu, Bin] Ningxia Med Univ, Sch Basic Med Sci, Dept Physiol & Pathophysiol, NHC Key Lab Metab Cardiovasc Dis Res, Yinchuan 750004, Peoples R China.;[Zhu, Haimei] Hunan Univ Chinese Med, Hosp 1, Dept Pain, Changsha 410007, Peoples R China.
通讯机构:
[Liu, B ; Long, Y ] H;Hunan Univ Chinese Med, Hosp 1, Branch Natl Clin Res Ctr Chinese Med Cardiol, Dept Cardiol, Changsha 410007, Peoples R China.;Hunan Univ, Coll Biol, Changsha 410082, Peoples R China.;Ningxia Med Univ, Sch Basic Med Sci, Dept Physiol & Pathophysiol, NHC Key Lab Metab Cardiovasc Dis Res, Yinchuan 750004, Peoples R China.
关键词:
Atherosclerosis;Evolocumab;Proprotein convertase subtilisin/Kexin type 9;Liposome;Phenotypic transition
摘要:
PCSK9, which is closely related to atherosclerosis, is significantly expressed in vascular smooth muscle cells (VSMCs). Moreover, Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) mediated phenotypic transformation, abnormal proliferation, and migration of VSMCs play key roles in accelerating atherosclerosis. In this study, by utilizing the significant advantages of nano-materials, a biomimetic nanoliposome loading with Evolocumab (Evol), a PCSK9 inhibitor, was designed to alleviate atherosclerosis. In vitro results showed that (Lipo + M)@E NPs up-regulated the levels of α-SMA and Vimentin, while inhibiting the expression of OPN, which finally result in the inhibition of the phenotypic transition, excessive proliferation, and migration of VSMCs. In addition, the long circulation, excellent targeting, and accumulation performance of (Lipo + M)@E NPs significantly decreased the expression of PCSK9 in serum and VSMCs within theplaque of ApoE(-/-) mice.
摘要:
Glioma is the most common malignancy in the central nervous system. This study aims to disclose the impacts of Xihuang pill (XHP), a traditional Chinese formula, on glioma cell pyroptosis and relevant molecular mechanism. U251 and SHG-44 cells were treated with XHP alone or together with oe-POU4F1 and sh-STAT3. CCK8 assay detected the viability, flow cytometry evaluated pyroptosis, and microscopy observed cell morphology. LDH release was determined by the LDH kit and the levels of IL-1β and IL-18 were detected by ELISA. Immunofluorescence showed NLRP3 expression in glioma cells and western blotting measured the levels of POU4F1, STAT3, NLRP3, ASC, cleaved caspase-1, and IL-1β. The binding of POU4F1 to STAT3 was verified. Primary glioma model was established to observe tumor change by in vivo imaging, determine the levels of Ki67 and NLRP3 by immunochemistry, and detect relevant protein levels by western blotting. XHP treatment alone downregulated POU4F1 and STAT3 levels, aroused pyroptotic appearance in glioma cells such as ballooning swelling, reduced cell viability and number of pyroptotic cells, increased LDH release and IL-1β and IL-18 levels, formed NLRP3 sports in cells, and elevated the levels of pyroptosis-related proteins. However, POU4F1 overexpression or STAT3 silencing suppressed XHP-promoted pyroptosis. Mechanistically, POU4F1 acted as a transcription factor of STAT3 and regulated its transcription. In primary glioma models, XHP enhanced glioma cell pyroptosis and blocked glioma growth. XHP facilitates glioma cell pyroptosis via the POU4F1/STAT3 axis.
摘要:
Background: Chronic heart failure (CHF) is a common and difficult-to-treat disease in clinical practice. The efficacy and safety of Zhenyuan capsule (ZYC) in the treatment of CHF were evaluated by meta-analysis and trial sequential analysis (TSA) of published relevant data. Methods: Searched 8 databases for clinical literature on ZYC in the treatment of CHF, up to December 2022. Then the meta-analysis and TSA were performed on the studies that met the inclusion criteria. Results: Meta-analysis showed that compared with conventional treatment, combined use of ZYC could significantly increase the clinical effective rate (risk ratio 1.20, 95% confidence interval [CI] 1.14 similar to 1.26, P < .00001) by 20%, left ventricular ejection fraction (MD 8.85, 95%CI 4.57 similar to 13.12, P < .0001) by 8.85%, and 6-minutes walking distance (MD 47.91, 95%CI 18.66 similar to 77.17, P = .001) by 47.91 m, and significantly reduce brain natriuretic peptide (MD -247.86, 95%CI -330.62 similar to-165.09, P < .00001) by 247.86 pg/mL. TSA showed that the benefits suggested by the original results were conclusive. In terms of safety, the total adverse events in the combined group of ZYC were comparable to those in the conventional group, and TSA demonstrated that this result needed more research and demonstration. Conclusion: ZYC can effectively improve the clinical efficacy of treating CHF, significantly increase left ventricular ejection fraction and 6-minute walk distance, and remarkably reduce brain natriuretic peptide. ZYC, with definite efficacy and safety, has the value of clinical application and in-depth research.
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:
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.
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:
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.
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
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:
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:
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.
期刊:
BMC Complementary Medicine and Therapies,2023年23(1):1-19 ISSN:2662-7671
通讯作者:
Wang, YH;Ge, JW
作者机构:
[Meng, Pan; Xie, Ming-xia; Luo, Yan; Wang, Yu-hong; Liu, Tong-tong; Zhong, Zi-yan] Hunan Univ Chinese Med, 300 Xueshi Rd, Hanpu Sci & Educ Pk, Changsha, Hunan, Peoples R China.;[Zhang, Xi; Guo, Dong-wei] Second Peoples Hosp Hunan Prov, Changsha, Hunan, Peoples R China.;[Yang, Hui; Liu, Jian] Hunan Univ Chinese Med, Affiliated Hosp 1, Changsha, Hunan, Peoples R China.;[Fang, Rui; Ge, Jin-Wen] Hunan Acad Chinese Med, 58 Lushan Rd, Changsha, Hunan, Peoples R China.
通讯机构:
[Wang, YH ; Ge, JW ] H;Hunan Univ Chinese Med, 300 Xueshi Rd, Hanpu Sci & Educ Pk, Changsha, Hunan, Peoples R China.;Hunan Acad Chinese Med, 58 Lushan Rd, Changsha, Hunan, Peoples R China.
关键词:
Xiaoyaosan;Depression;Whole transcriptomic analysis;Synapse loss;BDNF/trkB/PI3K signal axis
摘要:
BACKGROUND: Depression is a neuropsychiatric disease resulting from deteriorations of molecular networks and synaptic injury induced by stress. Traditional Chinese formula Xiaoyaosan (XYS) exert antidepressant effect, which was demonstrated by a great many of clinicalandbasicinvestigation. However, the exact mechanism of XYS has not yet been fully elucidated. METHODS: In this study, chronic unpredictable mild stress (CUMS) rats were used as a model of depression. Behavioral test and HE staining were used to detect the anti-depressant effects of XYS. Furthermore, whole transcriptome sequencing was employed to establish the microRNA (miRNA), long non-coding RNA (lncRNA), circular RNA (circRNA), and mRNA profiles. The biological functions and potential mechanisms of XYS for depression were gathered from the GO and KEGG pathway. Then, constructed the competing endogenous RNA (ceRNA) networks to illustrate the regulatory relationship between non-coding RNA (ncRNA) and mRNA. Additionally, longest dendrite length, total length of dendrites, number of intersections, and density of dendritic spines were detected by Golgi staining. MAP2, PSD-95, SYN were detected by immunofluorescence respectively. BDNF, TrkB, p-TrkB, PI3K, Akt, p-Akt were measured by Western Blotting. RESULTS: The results showed that XYS could increase the locomotor activity and sugar preference, decreased swimming immobility time as well as attenuate hippocampal pathological damage. A total of 753 differentially expressed lncRNAs (DElncRNAs), 28 circRNAs (DEcircRNAs), 101 miRNAs (DEmiRNAs), and 477 mRNAs (DEmRNAs) were identified after the treatment of XYS in whole transcriptome sequencing analysis. Enrichment results revealed that XYS could regulate multiple aspects of depression through different synapse or synaptic associated signal, such as neurotrophin signaling and PI3K/Akt signaling pathways. Then, vivo experiments indicated that XYS could promote length, density, intersections of synapses and also increase the expression of MAP2 in hippocampal CA1, CA3 regions. Meanwhile, XYS could increase the expression of PSD-95, SYN in the CA1, CA3 regions of hippocampal by regulating the BDNF/trkB/PI3K signal axis. CONCLUSION: The possible mechanism on synapse of XYS in depression was successfully predicted. BDNF/trkB/PI3K signal axis were the potential mechanism of XYS on synapse loss for its antidepressant. Collectively, our results provided novel information about the molecular basis of XYS in treating depression.
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.