作者机构:
[Kuang, Gaoyan; Lu, Min; Xu, Xiaotong; Wen, Zhi] Hunan Univ Chinese Med, Hosp 1, Dept Joint Orthoped, Changsha 410000, Hunan, Peoples R China.;[Qiu, Liguo; Wen, Zhi; Liu, Enxu] Hunan Univ Chinese Med, Changsha, Hunan, Peoples R China.;[Jiang, Yong; Wu, Yuyuan] Tradit Chinese Med Hosp Huaihua, Dept Pediat Orthoped, Huaihua, Hunan, Peoples R China.
通讯机构:
[Lu, M ] H;Hunan Univ Chinese Med, Hosp 1, Dept Joint Orthoped, Changsha 410000, Hunan, Peoples R China.
关键词:
aneurysmal bone cyst (ABC);autogenous fibula transplantation;case report
摘要:
RATIONALE: Aneurysmal bone cyst (ABC) is a rare primary or secondary tumor that usually occurs in young women aged between 10 and 20 years, mostly in the long tubular bone and spine. However, there are no definite standards for its clinical treatment. To our knowledge, this is the first report of a young female patient with distal radius ABC who was successfully treated with tumor resection and autogenous fibular head transplantation. PATIENT CONCERNS: A 28-year-old married Chinese young woman presented to our hospital with swelling and pain in her right wrist for 2 years and aggravation of wrist movement restriction for 1 week. DIAGNOSES: Pathological biopsy confirmed ABC. INTERVENTIONS: We performed a pathological examination of the tumor on the right wrist and preliminarily confirmed the diagnosis of ABC. The right wrist joint was reconstructed by total surgical resection of the ABC tumor in the right wrist joint and autogenous fibular head transplantation. OUTCOMES: During follow-up within 7 years, good right wrist function was confirmed. The tumor did not recur, the swelling of the right wrist disappeared, the joint pain and limitation of movement significantly improved, and the function of the right wrist was not impaired in daily activities. Radiography showed that the fracture had healed. LESSONS: Our results suggest that autofibular head transplantation is an effective treatment for reconstruction of wrist function in adult patients with ABC of the distal radius.
通讯机构:
[Deng, CQ; She, Y ; Shao, L ] H;Hunan Univ Chinese Med, Changsha 410208, Peoples R China.;Hunan Univ Chinese Med, Hosp 1, Changsha 410208, Hunan, Peoples R China.
摘要:
Ethnopharmacological relevance: A classic stroke formula is Buyang Huanwu Decoction (BYHWD), Glycosides are the pharmacological components found in BYHWD, which are utilized for the prevention and management of cerebral ischemia-reperfusion (CIR), as demonstrated in a previous study. Its neuroprotective properties are closely related to its ability to modulate inflammation, but its mechanism is as yet unclear. Aim of the study: A research was undertaken to investigate the impact of glycosides on the inflammation of CIR through the PTEN-induced putative kinase-1 (PINK1)/Parkin mitophagy pathway. Materials and methods: Analyzing glycosides containing serum components was performed with ultraperformance liquid chromatography-quadrupole-time of flight-mass spectrometry (UPLC-Q-TOF-MS). Glycosides were applied to rat of Middle cerebral artery occlusion/reperfusion (MCAO/R) model and primary neural cell of Oxygen glucose deprivation/reperfusion (OGD/R) model. The neuroprotective effect and the regulation of mitophagy of glycosides were evaluated through neural damage and PINK1/Parkin mitophagy activation. Moreover, the assessment of the relationship between glycosides regulation of mitophagy and its antiinflammatory effects subsequent to mitophagy blockade was conducted by examining neural damage, PINK1/ Parkin mitophagy activation, and levels of pyroptosis. Results: (1) It was observed that the administration of glycosides resulted in a decrease in neurological function scores, a reduction in cerebral infarction volume, an increase in mitochondrial autophagosome, and the maintenance of a high expression status of light chain 3 (LC3) II/LC3I protein. Additionally, there was a significant inhibition of p62 protein expression and an enhancement of PINK1 and Parkin protein expression. Furthermore, it was found that the effect of glycosides at a dosage of 0.128 g center dot kg-1 was significantly superior to that of glycosides at a dosage of 0.064 g center dot kg-1. Notably, the neuroprotective effect and inhibition of pyroptosis protein of glycosides at a dosage of 0.128 g center dot kg-1 were attenuated when mitochondrial autophagy was blocked. (2) Glycosides repaired cellular morphological damage, enhanced cell survival, and reduced Lactate dehydrogenase (LDH) leakage, with glycosides (2.36 mu g center dot mL-1 and 4.72 mu g center dot mL-1) neuronal protection being the strongest. Glycosides (4.72 mu g center dot mL-1) maintained LC3II/LC3I protein high expression state, inhibited p62 protein expression, and promoted PINK1 and Parkin protein expression, which was stronger than glycosides (2.36 mu g center dot mL-1). The blockade of mitophagy resulted in a reduction of neuroprotection and inhibition of pyroptosis protein exerted by glycosides. Conclusion: Glycosides demonstrate the ability to hinder inflammation through the activation of the PINK1/ Parkin mitophagy pathway, thereby leading to subsequent neuroprotective effects on CIR.
摘要:
Ulcerative colitis is a common digestive disorder worldwide, with increasing incidence in recent years. It is an urgent problem to be solved, as it seriously affects and threatens the health and life of the global population. Studies have shown that dysfunction of the intestinal mucosal barrier is a critical pathogenic factor and molecular basis of ulcerative colitis, and some scholars have described it as a "barrier organ disease." While the Notch signalling pathway affects a series of cellular processes, including proliferation, differentiation, development, migration, and apoptosis. Therefore, it can regulate intestinal stem cells, CD4(+) T cells, innate lymphoid cells, macrophages, and intestinal microbiota and intervene in the chemical, physical, immune, and biological mucosal barriers in cases of ulcerative colitis. The Notch signalling pathway associated with the pathogenesis of ulcerative colitis has distinct characteristics, with good regulatory effects on the mucosal barrier. However, research on ulcerative colitis has mainly focused on immune regulation, anti-inflammatory activity, and antioxidant stress; therefore, the study of the Notch signalling pathway suggests the possibility of understanding the pathogenesis of ulcerative colitis from another perspective. In this article we explore the role and mechanism of the Notch signalling pathway in the pathogenesis of ulcerative colitis from the perspective of the intestinal mucosal barrier to provide new targets and theoretical support for further research on the pathogenesis and clinical treatment of ulcerative colitis.
摘要:
BACKGROUND The effects of viral hepatitis (VH) on type 2 diabetes (T2D) remain controversial. AIM To analyze the causal correlation between different types of VH and T2D using Mendelian randomization (MR). METHODS Single nucleotide polymorphisms of VH, chronic hepatitis B (CHB), chronic hepatitis C (CHC) and T2D were obtained from the BioBank Japan Project, European Bioinformatics Institute, and FinnGen. Inverse variance weighted, MR-Egger, and weighted median were used to test exposure-outcome associations. The MR-Egger intercept analysis and Cochran's Q test were used to assess horizontal pleiotropy and heterogeneity, respectively. Leave-one-out sensitivity analysis was used to evaluate the robustness of the MR analysis results. RESULTS The MR analysis showed no significant causal relationship between VH and T2D in Europeans [odds ratio (OR) = 1.028; 95% confidence interval (CI): 0.995-1.062, P = 0.101]. There was a negative causal association between CHB and T2D among East Asians (OR = 0.949; 95%CI: 0.931-0.968, P < 0.001), while there was no significant causal association between CHC and T2D among East Asians (OR = 1.018; 95%CI: 0.959-1.081, P = 0.551). Intercept analysis and Cochran's Q test showed no horizontal pleiotropy or heterogeneity (P > 0.05). Sensitivity analysis showed that the results were robust. CONCLUSION Among East Asians, CHB is associated with a reduced T2D risk, but this association is limited by HBV load and cirrhosis. Although VH among Europeans and CHC among East Asians are not associated with the risk of T2D, focusing on blood glucose in patients with CHC is still relevant for the early detection of T2D induced by CHC-mediated pathways of hepatic steatosis, liver fibrosis, and cirrhosis.
摘要:
Object: The benefits of low-dose esketamine for painless gastrointestinal endoscopy remain unclear. As such, the present study aimed to investigate the efficacy and safety of low-dose esketamine for this procedure. Methods: Seven common databases were searched for clinical studies investigating low-dose esketamine for painless gastrointestinal endoscopy. Subsequently, a meta-analysis was performed to synthesize and analyze the data extracted from studies fulfilling the inclusion criteria. Results: Meta-analysis revealed that, compared with propofol, low-dose esketamine in combination with propofol significantly reduced recovery time by 0.56 min (mean difference [MD] -0.56%, 95% confidence interval (CI) -1.08 to -0.05, p = 0.03), induction time by 9.84 s (MD -9.84, 95% CI -12.93 to -6.75, p < 0.00001), propofol dosage by 51.05 mg (MD -51.05, 95% CI -81.53 to -20.57, p = 0.01), and increased mean arterial pressure by 6.23 mmHg (MD 6.23, 95% CI 1.37 to 11.08, p = 0.01). Meanwhile, low-dose esketamine reduced injection pain by 63% (relative risk [RR] 0.37, 95% CI 0.28 to 0.49, p < 0.00001), involuntary movements by 40% (RR 0.60, 95% Cl 0.42 to 0.85, p < 0.005), choking by 42% (RR 0.58, 95% Cl 0.38 to 0.88, p = 0.01), bradycardia by 68% (RR 0.32, 95% Cl 0.18 to 0.58, p = 0.0002), hypotension by 71% (RR 0.29, 95% Cl 0.21 to 0.40, p < 0.00001), respiratory depression by 63% (RR 0.37, 95% 0.26 to 0.51, p < 0.00001), additional cases of propofol by 53% (RR 0.47, 95% Cl 0.29 to 0.77, p = 0.002), and increased hypertension by 1000% (RR 11.00, 95% Cl 1.45 to 83.28, p = 0.02). There were no significant differences in mean heart rate, mean oximetry saturation, delirium, dizziness, vomiting, tachycardia, and hypoxemia. Subgroup analyses revealed that, compared with other dose groups, 0.25 mg/kg esketamine afforded additional benefits in recovery and induction time, mean arterial pressure, involuntary movements, hypoxemia, and respiratory depression. Conclusion: Low-dose esketamine was found to be safe and effective for providing anesthesia during gastrointestinal endoscopy, with 0.25 mg/kg identified as the optimal dose within the dosage ranges examined. However, caution should be exercised when administering this drug to patients with inadequate preoperative blood pressure control.
摘要:
Objective The specific benefit and selection of acupoints in acupuncture for diabetic kidney disease (DKD) remains controversial. This study aims to explore the specific benefits and acupoints selection of acupuncture for DKD through meta-analysis and data mining. Methods Clinical trials of acupuncture for DKD were searched in eight common databases. Meta-analysis was used to evaluate its efficacy and safety, and data mining was used to explore its acupoints selection. Results Meta-analysis displayed that compared with the conventional drug group, the combined acupuncture group significantly increased the clinical effective rate (risk ratio [RR] 1.35, 95% confidence interval [CI] 1.20 to 1.51, P < 0.00001) and high-density lipoprotein cholesterol (mean difference [MD] 0.36, 95% CI 0.27 to 0.46, P < 0.00001), significantly reduced the urinary albumin (MD -0.39, 95% CI -0.42 to -0.36, P < 0.00001), urinary microalbumin (MD -32.63, 95% CI -42.47 to -22.79, P < 0.00001), urine beta 2-microglobulin (MD -0.45, 95% CI -0.66 to -0.24, P < 0.0001), serum creatinine (MD -15.36, 95% CI -21.69 to -9.03, P < 0.00001), glycated hemoglobin A1c (MD -0.69, 95% CI -1.18 to -0.19, P = 0.006), fasting blood glucose (MD -0.86, 95% CI -0.90 to -0.82, P < 0.00001), 2h postprandial plasma glucose (MD -0.87, 95% CI -0.92 to -0.82, P < 0.00001), total cholesterol (MD -1.23, 95% CI -2.05 to -0.40, P = 0.003), triglyceride (MD -0.69, 95% CI -1.23 to -0.15, P = 0.01), while adverse events were comparable. Data mining revealed that CV12, SP8, SP10, ST36, SP6, BL20, BL23, and SP9 were the core acupoints for DKD treated by acupuncture. Conclusion Acupuncture improved clinical symptoms, renal function indices such as uALB, umALB, u beta 2-MG, and SCR, as well as blood glucose and blood lipid in patients with DKD, and has a favorable safety profile. CV12, SP8, SP10, ST36, SP6, BL20, BL23, and SP9 are the core acupoints for acupuncture in DKD, and this program is expected to become a supplementary treatment for DKD.
摘要:
is an early event of brain injury after subarachnoid hemorrhage (SAH). Whether the macrophage mediators in resolving inflammation 1 (MaR1) is involved in SAH pathogenesis is unknown. In this study, 205 male Sprague-Dawley rats were subjected to SAH via endovascular perforation in the experimental and control groups. MaR1 was dosed intranasally at 1 h after SAH, with LGR6 siRNA and KG -501, GSK-J4 administered to determine the signaling pathway. Neurobehavioral, histological and biochemical data were obtained from the animal groups with designated treatments. The results showed: (i) The leucine-rich repeat containing G protein-coupled receptor 6 (LGR6) was decreased after SAH and reached to the lowest level at 24 h after SAH. Jumonji d3 (JMJD3) protein levels tended to increase and peaked at 24 h after SAH. LGR6 and JMJD3 expression were co-localized with microglia. (ii) MaR1 administration mitigated short-term neurological deficits, brain edema and long-term neurobehavioral performance after SAH, and attenuated microglial activation and neutrophil infiltration. (iii) Knockdown of LGR6, inhibition of CREB phosphorylation or JMJD3 activity abolished the antineuroinflammatory effect of MaR1 on the expression of CREB, CBP, JMJD3, IRF4, IRF5, IL -1b, IL -6 and IL -10, thus prevented microglial activation and neutrophil infiltration. Together, the results show that MaR1 can activate LGR6 and affect CREB/JMJD3/IRF4 signaling to attenuate neuroinflammation after SAH, pointing to a potential pharmacological utility in this disorder.(c) 2024 IBRO. Published by Elsevier Inc. All rights reserved.
期刊:
Drug Design, Development and Therapy,2024年18:699-717 ISSN:1177-8881
通讯作者:
Guo, C
作者机构:
[Zhou, Xuqing; Guo, C; Wang, Xu; Guo, Chun; Lei, Shihui; Yang, Yi] Hunan Univ Chinese Med, Hosp 1, Expt Ctr Med Innovat, Changsha 410007, Hunan, Peoples R China.;[Zhou, Xuqing; Guo, C; Wang, Xu; Guo, Chun] Hunan Univ Chinese Med, Clin Coll Tradit Chinese Med 1, Changsha 410007, Hunan, Peoples R China.;[Li, Jiaqi; He, Ying; Yang, Hua] Hunan Agr Univ, Coll Biosci & Biotechnol, Changsha 410128, Hunan, Peoples R China.;[Zhang, Mengxue; Zhou, Desheng] Hunan Univ Chinese Med, Hosp 1, Dept Neurol, Changsha 410007, Hunan, Peoples R China.
通讯机构:
[Guo, C ] H;Hunan Univ Chinese Med, Hosp 1, Expt Ctr Med Innovat, Changsha 410007, Hunan, Peoples R China.;Hunan Univ Chinese Med, Clin Coll Tradit Chinese Med 1, Changsha 410007, Hunan, Peoples R China.
摘要:
BACKGROUND: Annao Pingchong decoction (ANPCD) is a traditional Chinese decoction which has definite effects on treating intracerebral hemorrhage (ICH) validated through clinical and experimental studies. However, the impact of ANPCD on oxidative stress (OS) after ICH remains unclear and is worth further investigating. AIM: To investigate whether the therapeutic effects of ANPCD on ICH are related to alleviating OS damage and seek potential targets for its antioxidant effects. MATERIALS AND METHODS: The therapeutic candidate genes of ANPCD on ICH were identified through a comparison of the target genes of ANPCD, target genes of ICH and differentially expressed genes (DEGs). Protein-protein interaction (PPI) network analysis and functional enrichment analysis were combined with targets-related literature to select suitable antioxidant targets. The affinity between ANPCD and the selected target was verified using macromolecular docking. Subsequently, the effects of ANPCD on OS and the selected target were further investigated through in vivo experiments. RESULTS: Forty-eight candidate genes were screened, in which silent information regulator sirtuin 1 (SIRT1) is one of the core genes that has antioxidant effects and ICH significantly affected its expression. The good affinity between 6 compounds of ANPCD and SIRT1 was also demonstrated by macromolecular docking. The results of in vivo experiments demonstrated that ANPCD significantly decreased modified neurological severity scoring (mNSS) scores and serum MDA and 8-OHdG content in ICH rats, while significantly increasing serum SOD and CAT activity, complicated with the up-regulation of ANPCD on SIRT1, FOXO1, PGC-1α and Nrf2. Furthermore, ANPCD significantly decreased the apoptosis rate and the expression of apoptosis-related proteins (P53, cytochrome c and caspase-3). CONCLUSION: ANPCD alleviates OS damage and apoptosis after ICH in rats. As a potential therapeutic target, SIRT1 can be effectively regulated by ANPCD, as are its downstream proteins.
期刊:
International Journal of Cardiology,2024年395:131400 ISSN:0167-5273
通讯作者:
Guo, ZH
作者机构:
[Zheng, Huizhen; Yin, Ziwei; Luo, Xi; Zhou, Yingli] Hunan Univ Chinese Med, Affiliated Hosp 1, Dept Cardiol, Changsha 410007, Peoples R China.;[Zheng, Huizhen; Yin, Ziwei; Zhang, Fei; Luo, Xi; Guo, Zhihua; Zhou, Yingli] Hunan Univ Chinese Med, Coll Chinese Med, Changsha 410208, Peoples R China.;[Guo, Zhihua] Coll Intelligent Tradit Chinese Med Diag & Prevent, Hunan Key Lab, Changsha 410208, Peoples R China.
通讯机构:
[Guo, ZH ] H;Hunan Univ Chinese Med, Coll Chinese Med, Changsha 410208, Peoples R China.
关键词:
Cross-sectional study;Heart failure;NHANES;Population-based study;Risk factors;Systemic immune-inflammation index
摘要:
BACKGROUND: Heart failure (HF) is a disease closely associated with inflammation, and the systemic immune-inflammation index (SII) is a novel inflammatory marker. Therefore, this study aims to explore the relationship between SII and HF. METHODS: We used National Health and Nutrition Examination Survey data from 1998 to 2018 to include adults who reported a diagnosis of HF and complete information on the calculation of SII. SII was calculated as platelet count × neutrophil count/lymphocyte count. We used multiple logistic regression models to examine the association between SII and HF and explored possible influencing factors by subgroup analysis. In addition, we performed smoothed curve fitting and threshold effect analysis to describe the nonlinear relationship. RESULTS: The population-based study involved a total of 48,155 adults ages 20-85. Multivariate logistic regression showed that participants with the highest SII had a statistically significant 32% increased risk of HF prevalence compared to those with the lowest SII (OR=1.32; 95% CI, 1.06-1.65, P=0.0144) in a fully adjusted model. Subgroup analysis revealed no significant interactions between SII and specific subgroups (p>0.05 for all interactions). Furthermore, the association between SII and HF was non-linear; the inflection point was 1104.78 (1000 cells/μl). CONCLUSIONS: Based on our findings, elevated SII levels were found to be strongly associated with the risk of HF, and SII was nonlinearly associated with HF. To validate these findings, a larger prospective investigation is needed to support the results of this study and investigate potential problems.
关键词:
Qingguang'an;Autophagy;Fibrosis;Scar formation;Glaucoma filtering surgery
摘要:
Purpose: To investigate the mechanism by which Qingguang'an inhibits scar formation in rabbits administered glaucoma filtering surgery (GFS). Methods: Combined trabeculectomy was performed in 100 rabbits diagnosed with glaucoma, which were assigned to five groups, including the no surgery, surgery only, mitomycin C (MMC; positive control), Qingguang'an (experimental) and PBS (negative control) groups. The animals were followed up at postoperative days 1-28. Ultrastructure was observed under a transmission electron microscope (TEM). Real -Time Polymerase Chain Reaction (RT-PCR), Western blot, Hematoxylin and Eosin (H&E) staining, Masson's trichrome staining and Immuno-histochemistry (IHC) were performed to assess the harvested blocks. Results: In the Qingguang'an group, intraocular pressure (IOP) on postoperative D28 was significantly lower than values in the no surgery, surgery only and PBS groups (P < 0.05). Its blebs kept better filtering function and less complications in follow-up, which be detected to have less fibroblasts and collagen deposition histologically. Compared with the PBS group, ATG5, Beclin1 and LC3-II mRNA levels were significantly increased while P62 was downregulated in the Qingguang'an group (P < 0.05). Correspondingly, ATG5 and Beclin1 protein amounts in the Qingguang'an group were increased while P62 was downregulated. The LC3-II/I ratio tended to rise to the process of autophagy. Abundant autophagosomes were captured under TEM in this condition. Conclusions: Qingguang'an granules can inhibit scar formation in rabbits after GFS and restrain IOP increase by inducing autophagy in TFs. (c) 2023 Center for Food and Biomolecules, National Taiwan University. Production and hosting by Elsevier Taiwan LLC. This is an open access article under the CC BY -NC -ND license (http://creativecommons.org/li censes/by-nc-nd/4.0/).
通讯机构:
[Shi, LR ] ;Cent South Univ, Xiangya Hosp, Dept Radiol, 87 Xiangya Rd, Changsha 410005, Peoples R China.
摘要:
PURPOSE: To assess the safety and efficacy of local ablation plus PD-1 inhibitor toripalimab in previously treated unresectable hepatocellular carcinoma (HCC). PATIENTS AND METHODS: In the multicenter, two-stage, and randomized phase 1/2 trial, patients were randomly assigned to receive toripalimab alone (240 mg, every 3 weeks), subtotal local ablation followed by toripalimab starting on post-ablation day 3 (Schedule D3), or on post-ablation day 14 (Schedule D14). The first endpoint of stage 1 was to determine which combination schedule could continue and progression-free survival (PFS) as the primary endpoint for stage 1/2. RESULTS: A total of 146 patients were recruited. During stage 1, Schedule D3 achieved numerically higher objective response rate (ORR) than Schedule D14 for non-ablation lesions (37.5% vs. 31.3%), and was chosen for stage 2 evaluation. For the entire cohort of both stages, patients with Schedule D3 had a significantly higher ORR than with toripalimab alone (33.8% vs. 16.9%; P = 0.027). Moreover, patients with Schedule D3 had improved median PFS (7.1 vs. 3.8 months; P < 0.001) and median overall survival (18.4 vs. 13.2 months; P = 0.005), as compared with toripalimab alone. In addition, six (9%) patients with toripalimab, eight (12%) with Schedule D3, and 4 (25%) with Schedule D14 developed grade 3 or 4 adverse events, and one patient (2%) with Schedule D3 manifested grade 5 treatment-related pneumonitis. CONCLUSIONS: In patients with previously treated unresectable HCC, subtotal ablation plus toripalimab improved the clinical efficacy as compared with toripalimab alone, with an acceptable safety profile.
期刊:
Frontiers in Pharmacology,2023年14:1137609 ISSN:1663-9812
通讯作者:
Liu, BY;Yuan, CY
作者机构:
[Yi, Jian; Tian, Fengming; Xu, Yaqian; Liu, Baiyan; Liu, BY; Chen, Bowei; Ouyang, Yin; Liu, Yingfei] Hunan Univ Chinese Med, Hosp 1, Changsha, Peoples R China.;[Yi, Jian; Tian, Fengming; Xu, Yaqian; Liu, Baiyan; Liu, BY; Chen, Bowei; Ouyang, Yin; Liu, Yingfei] Hunan Univ Chinese Med, MOE Key Lab Res & Translat Prevent & Treatment Maj, Changsha, Peoples R China.;[Yuan, Chunyun] Hunan Hosp Integrated Tradit Chinese & Western Med, Changsha, Peoples R China.;[Yuan, Chunyun] Hunan Acad Chinese Med, Affiliated Hosp, Changsha, Peoples R China.;[Liu, Baiyan; Liu, BY] Hunan Acad Chinese Med, Changsha, Peoples R China.
通讯机构:
[Liu, BY ; Yuan, CY ] H;Hunan Univ Chinese Med, Hosp 1, Changsha, Peoples R China.;Hunan Univ Chinese Med, MOE Key Lab Res & Translat Prevent & Treatment Maj, Changsha, Peoples R China.;Hunan Hosp Integrated Tradit Chinese & Western Med, Changsha, Peoples R China.;Hunan Acad Chinese Med, Affiliated Hosp, Changsha, Peoples R China.
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:
Microcystin (MC) is the byproduct of cyanobacteria metabolism that is associated with oxidative stress and heart damage. This study aimed to investigate the effect of ginsenoside Rg3 on MC-induced cardiotoxicity. A mouse model of myocardial infarction was constructed by oral MC administration. H9C2 cells were used for in vitro analysis. Cellular oxidative stress, apoptosis, and the relationship between miR-128-3p and double minute 4 protein (MDM4) were analyzed. MiR-128-3p expression was upregulated in vitro and in vivo after MC treatment, which was downregulated after Rg3 treatment. Left ventricular ejection fraction (LVEF) and left ventricular systolic pressure (LVSP) were increased and left ventricular end-diastolic pressure (LVEDP) was decreased after Rg3 treatment. Moreover, Rg3 alleviated MC-induced pathological changes and apoptosis in myocardial tissues. Meanwhile, Rg3 treatment decreased the lactate dehydrogenase (LDH) and malondialdehyde (MDA) levels and inhabited cell apoptosis and oxidative stress in MC-treated myocardial cells. MiR-128-3p overexpression attenuated the protective effect of Rg3 on MC-induced cardiotoxicity. MiR-128-3p negatively regulated MDM4 expression. This study revealed that Rg3 alleviated MC-induced cardiotoxicity through the miR-128-3p/MDM4 axis, which emphasized the potential of Rg3 as a therapeutic agent for MC-induced cardiotoxicity, and miR-128-3p as a target for the Rg3 therapy.
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:
Frontiers in Microbiology,2023年14:1208157 ISSN:1664-302X
通讯作者:
Song, HP;Zeng, Meiyan
作者机构:
[Song, Houpan; Yuan, Chengzhi; Xiong, Meng; Sun, Qifang; Yu, Chang] Hunan Univ Chinese Med, Hunan Prov Key Lab Tradit Chinese Med Diagnost, Changsha, Hunan, Peoples R China.;[Yuan, Chengzhi] Hunan Univ Chinese Med, Sch Med, Changsha, Hunan, Peoples R China.;[Zeng, Meiyan; Song, Houpan; Xiong, Meng; Sun, Qifang; Yu, Chang] Hunan Univ Chinese Med, Sch Tradit Chinese Med, Changsha, Hunan, Peoples R China.;[Zhou, Sainan] Hunan Univ Chinese Med, Affiliated Hosp 1, Changsha, Hunan, Peoples R China.
通讯机构:
[Zeng, MY; Song, HP ] H;Hunan Univ Chinese Med, Hunan Prov Key Lab Tradit Chinese Med Diagnost, Changsha, Hunan, Peoples R China.;Hunan Univ Chinese Med, Sch Tradit Chinese Med, Changsha, Hunan, Peoples R China.
摘要:
Resistance of Helicobacter pylori (H. pylori) to antibiotics has reached alarming levels worldwide, and the efficacy of the H. pylori eradication treatment has decreased dramatically because of antibiotic resistance. To gain a more comprehensive understanding of the development status, research hotspots, and future trends related to H. pylori antibiotic resistance, we conducted a thorough retrospective analysis via the bibliometrics method. We searched the Science Citation Index Expanded of the Web of Science Core Collection for all pertinent articles on H. pylori antibiotic resistance from 2013 to 2022. R-bibliometrix, CiteSpace, and VOSviewer tools were utilized to depict statistical evaluations in order to provide an unbiased presentation and forecasts in the field. We incorporated a total of 3,509 articles related to H. pylori antibiotic resistance. Publications were inconsistent prior to 2017, but steadily increased after 2017. China generated the most papers and the United States of America received the most citations and the highest H-index. Baylor College of Medicine was the most influential institution in this field, with the highest number of publications and citations, as well as the highest H-index. Helicobacter was the most productive journal, followed by the World Journal of Gastroenterology and Frontiers in Microbiology. The World Journal of Gastroenterology had the highest citation. Graham, David Y was the most productive and cited author. Clarithromycin resistance, prevalence, gastric cancer, quadruple therapy, sequential therapy, 23S rRNA, whole genome sequencing, bismuth, and probiotics appeared with a high frequency in the keywords. The top keywords with the highest citation bursts were vonoprazan, RdxA, biofilm formation, and fatty acid chain. Our research illustrated a multi-dimensional facet and a holistic knowledge structure for H. pylori antibiotic resistance research over the past decade, which can serve as a guide for the H. pylori research community to conduct in-depth investigations in the future.
期刊:
FRONTIERS IN ONCOLOGY,2023年12:1050756 ISSN:2234-943X
通讯作者:
Cao, J.;Jiang, X.;Cho, W.C.
作者机构:
[Zhou, Fang] Hunan Univ Chinese Med, Changsha, Peoples R China.;[Zhang, Zhen; Zhou, Fang] Hunan Acad Tradit Chinese Med, Affiliated Hosp, Dept Oncol, Changsha, Peoples R China.;[Zeng, Lingfeng] Prince Wales Hosp, Carol & Richard Yu Peritoneal Dialysis Res Ctr, Dept Med & Therapeut, Shatin, Hong Kong, Peoples R China.;[Zeng, Lingfeng] Chinese Univ Hong Kong, Li Ka Shing Inst Hlth Sci LiHS, Fac Med, Shatin, Hong Kong, Peoples R China.;[Chen, Xi; Zhao, Jinxi; Huang, Xiaobin; Tian, Jintao; Liu, Xujie; Yao, Huayi; Wang, Heping; Pu, Jun] Kunming Med Univ, Dept Neurosurg, Affiliated Hosp 2, Kunming, Peoples R China.
通讯机构:
[Cho, W.C.; Cao, J.] D;[Jiang, X.] K;Department of Clinical Oncology, Hong Kong;Department of Oncology, China;Kunming College of Life Science, China
摘要:
Dual-specificity phosphatase 10 (DUSP10) correlates with inflammation, cytokine secretion, cell proliferation, survival, and apoptosis. However, its role in glioma is unclear. Herein, we sought to examine the expression and the underlying carcinogenic mechanisms of DUSP10 action in glioma. DUSP10 expression in glioma was significantly higher than that in normal brain tissues. High DUSP10 expression indicated adverse clinical outcomes in glioma patients. Increased DUSP10 expression correlated significantly with clinical features in glioma. Univariate Cox analysis showed that high DUSP10 expression was a potential independent marker of poor prognosis in glioma. Furthermore, DUSP10 expression in glioma correlated negatively with its DNA methylation levels. DNA methylation level of DUSP10 also correlated negatively with poor prognosis in glioma. More importantly, DUSP10 expression correlated positively with the infiltration of B cells, CD4+ T cells, CD8+ T cells, neutrophils, macrophages, and dendritic cells in glioma. Gene set enrichment analysis (GSEA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis confirmed that DUSP10 participated in signaling pathways involved in focal adhesion, TNF cascade, Th17 cell differentiation, and NF-kappa B cascade. Finally, we uncovered that DUSP10 was dramatically upregulated in glioblastoma (GBM) cells and that the knockdown of DUSP10 inhibited glioma cell proliferation and migration. Our findings suggested that DUSP10 may serve as a potential prognostic biomarker in glioma.
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.
摘要:
Background: Among the 382 million diabetic patients worldwide, approximately 30% experience neuropathy, and one-fifth of these patients eventually develop diabetes cognitive impairment (CI). However, the mechanism underlying diabetes CI remains unknown, and early diagnostic methods or effective treatments are currently not available.Objective: This study aimed to explore the risk factors for CI in patients with type 2 diabetes mellitus (T2DM), screen potential therapeutic drugs for T2DM-CI, and provide evidence for preventing and treating T2DM-CI.Methods: This study focused on the T2DM population admitted to the First Affiliated Hospital of Hunan College of Traditional Chinese Medicine and the First Affiliated Hospital of Hunan University of Chinese Medicine. Sociodemographic data and clinical objective indicators of T2DM patients admitted from January 2018 to December 2022 were collected. Based on the Montreal Cognitive Assessment (MoCA) Scale scores, 719 patients were categorized into two groups, the T2DM-CI group with CI and the T2DM-N group with normal cognition. The survey content included demographic characteristics, laboratory serological indicators, complications, and medication information. Six machine learning algorithms were used to analyze the risk factors of T2DM-CI, and the Shapley method was used to enhance model interpretability. Furthermore, we developed a graph neural network (GNN) model to identify potential drugs associated with T2DM-CI.Results: Our results showed that the T2DM-CI risk prediction model based on Catboost exhibited superior performance with an area under the receiver operating characteristic curve (AUC) of 0.95 (specificity of 93.17% and sensitivity of 78.58%). Diabetes duration, age, education level, aspartate aminotransferase (AST), drinking, and intestinal flora were identified as risk factors for T2DM-CI. The top 10 potential drugs related to T2DM-CI, including Metformin, Liraglutide, and Lixisenatide, were selected by the GNN model. Some herbs, such as licorice and cuscutae semen, were also included. Finally, we discovered the mechanism of herbal medicine interventions in gut microbiota.Conclusion: The method based on Interpreting AI and GNN can identify the risk factors and potential drugs associated with T2DM-CI.