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Neuroinflammation is a common pathological feature of neurodegenerative diseases （NDs）. Microglia （MG）， a resident macrophage in the brain with a unique developmental origin， is the core driver of neuroinflammation. It can participate in the occurrence and development of NDs through different polarization states and play a key role in regulating neurogenesis and synapse shaping and maintaining homeostasis. MG can be divided into M1 pro-inflammatory phenotype and M2 anti-inflammatory phenotype according to its function. The inflammatory mediators released by the M1 phenotype can lead to nerve degeneration and myelin sheath damage， while the activation of the M2 phenotype is required to inhibit the inflammatory response and promote tissue repair. With the advantages of multi-pathway， multi-target， and bidirectional regulation， traditional Chinese medicine can regulate the polarization balance of MG and has dual effects on NDs such as Alzheimer's disease， Parkinson's disease， and multiple sclerosis. The active components of traditional Chinese medicine and its compound can inhibit the activation of MG by regulating phosphatidylinositol-3-kinases/protein kinase B（PI3K/Akt）， NOD-like receptor thermal protein domain associated protein 3（NLRP3）， signal transducer and activator of transcription factor1（STAT1）， nuclear transcription factor kappa B（NF-κB）， and other pathways， promote the polarization of M1 phenotype to M2 phenotype， reduce the expression of interleukin（IL）-6， tumor necrosis factor-α（TNF-α）， and other pro-inflammatory factors， and increase the secretion of IL-10， arginase-1（Arg-1）， and other anti-inflammatory factors. It can also reduce β-amyloid deposition and tau protein expression in Alzheimer's disease， alleviate dopaminergic neuronal damage in Parkinson's disease， and relieve demyelination， inflammatory cell infiltration， and related clinical symptoms of multiple sclerosis. The bidirectional regulation of the M1/M2 polarization balance of MG by traditional Chinese medicine is a potential strategy for the treatment of NDs. This paper focused on the targets of the regulation of MG polarization balance by traditional Chinese medicine monomer and its compound in the treatment of NDs， so as to further study and summarize the existing research results and provide ideas and basis for the future treatment of NDs.
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ObjectiveTo investigate the role of bile acid receptor TGR5 activation in renal fibrosis induced by unilateral ischemia reperfusion injury and contralateral nephrectomy （uIRIx） model. MethodsIn vivo： C57BL/6J mice were randomly divided into Sham group， uIRIx group and uIRIx+ lithcholic acid （LCA） group with 6 mice in each group. Kidney fibrosis was induced by uIRIx model， kidney function was evaluated by blood and urine biochemical indexes， and the degree of kidney injury was evaluated by HE staining. Masson staining and immunohistochemistry were used to evaluate the degree of renal fibrosis， and Western Blotting was used to detect the expression of related index proteins of renal cortical fibrosis. Sham group and uIRIx group were set in TGR5+/+ mice and TGR5-/- mice respectively， with 6 mice in each group. The degree of renal fibrosis in each group was detected by Western Blotting. In vitro： TGF-β1 was administered to induce pro-fibrosis response in human renal tubular epithelial cell line （HK2 cells）， LCA was used for drug intervention， cytoskeleton was labeled with phalloidin-FITC staining and the expression of fibrosis related indicator protein in HK2 cells was detected by Western Blotting. ResultsIn vivo： Compared with the Sham group， plasma creatinine level （P=0.007） and urinary albumin/creatinine ratio （P=0.041） in uIRIx group were significantly increased， renal cortical protein TGR5 expression （P=0.002） was decreased， Fibronectin expression （P=0.020） and COL1A1 expression （P<0.001） were increased. At the same time， the kidney structure was damaged and collagen deposition was aggravated. LCA intervention effectively improved the kidney function and alleviated the degree of kidney injury and fibrosis. TGR5 gene knockout increased uIRIx-induced Fibronectin expression （P<0.001） and COL1A1 expression （P=0.001） compared with TGR5+/+ mice. In vitro： TGF-β1 induced morphological changes of HK2 cells， cytoskeletal depolymerization and recombination， and promoted the up-regulation of fibrosis index protein. LCA effectively inhibited the morphological changes and skeletal depolymerization induced by TGF-β1， and down-regulated the expression of fibrosis related indicator proteins. ConclusionsLCA alleviated renal fibrosis induced by uIRIx model， and knockout of TGR5 gene aggravated uIRIx induced renal fibrosis； In HK2 cells， LCA alleviated fibrogenic reaction induced by TGF-β1. This indicates that activation of TGR5 alleviates renal fibrosis induced by uIRIx.
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AIM:To explore the correlation and consistency of three tear assessment methods in the diagnosis of dry eye, which include the Schirmer Ⅰ test(SⅠt), tear meniscus height(TMH)measurement and a new generation of tear detection technology-Strip meniscometry tube(SMTube).METHODS: A diagnostic test study. A total of 183 dry eye outpatients(183 right eyes)in the Dry Eye Center of Henan Eye Hospital were enrolled from May to June 2021. The SⅠt, TMH and SMTube were performed on all patients, and the correlation and consistency of the measurement results were analyzed.RESULTS:The ocular surface disease index(OSDI)of all included patients was 43.75(31.25, 58.33), noninvasive breakup time(NIBUT)was 7.26(4.97, 9.37)s, and the results of SⅠt, TMH and SMTube were 6(2, 12)mm/5min, 0.18(0.14, 0.22)mm and 5(3,8)mm/5s, respectively; The results of correlation analysis: TMH was positively correlated with SMTube(rs=0.751, P<0.001), however, SⅠt had no correlation with TMH(rs=0.139, P=0.060)and SMTube(rs=0.019, P=0.799). The results of consistency analysis: TMH showed good consistency with SMTube(Kappa=0.794, P=0.044), however, SⅠt showed poor consistency with TMH(Kappa=0.271, P=0.074)and SMTube(Kappa=0.193, P=0.070)respectively.CONCLUSION:SMTube is a new, simple and convenient tool for evaluating tear volume. It has a good correlation and consistency with TMH measurement results. Therefore, it can replace TMH measurement, but cannot replace SⅠt in clinical application.
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Objective: To investigate the expression of cortactin in colorectal cancer and its correlation with clinicopathological parameters and prognosis. Methods: The expressions of cortactin in normal colorectal mucosal tissue and colorectal cancer tissue in paraffin-embedded tissue microarray from 319 patients who were diagnosed as colorectal cancer and treated in Cancer Hospital of Chinese Academy of Medical Sciences from 2006 to 2009 was detected by immunohistochemistry. Kaplan-Meier method and Log rank test were used for survival analysis, and Cox proportional risk regression model was used for multivariate analysis. Results: The positive expression rates of cortactin in colorectal cancer tissue and normal colorectal mucosal tissue were 61.1% (195/319) and 5.6% (18/319, P<0.001), respectively. T-stage, N-stage, American Joint Committee on Cancer (AJCC) stage, degree of tumor differentiation, neural invasion and preoperative carcinoembryonic antigen (CEA) levels were associated with the expression of cortactin (P<0.05). The positive expression of cortactin was associated with poorer disease-free survival (P=0.036) and overall survival (P=0.043), and the effect was more significant in patients with stage Ⅱ to Ⅲ. For patients with stage Ⅱ-Ⅲ colorectal cancer, postoperative adjuvant therapy was associated with disease-free survival (P=0.007) and overall survival (P=0.015). The vascular tumor embolus, pathological type, preoperative CEA level and cortactin expression were independent influencing factors for disease-free survival (P<0.05). The age, AJCC stage, preoperative CEA level and cortactin expression were independent influencing factors for overall survival (P<0.05). Preoperative CEA level and cortactin expression were independent influencing factors for disease-free survival and overall survival (P<0.05). Conclusion: Cortactin is expressed in colorectal cancer and in stage Ⅱ-Ⅲ patients, it is a potential predictor of colorectal cancer prognosis.
Subject(s)
Humans , Biomarkers, Tumor/metabolism , Carcinoembryonic Antigen/metabolism , Colorectal Neoplasms/pathology , Cortactin/metabolism , Prognosis , Retrospective StudiesABSTRACT
ObjectiveIopromide can induce injury to HK-2 cells, but its exact mechanism remains poorly understood. This study aimed to explore the influence of iopromide on ROS-NLRP3 inflammasome signaling in HK-2 cells.MethodsHK-2 human renal tubular epithelial cells were divided into six groups: control and iopromide at 37, 74, 111, 148 and 185 mgI/mL. The HK-2 cells in the latter five groups were treated with different concentrations of iopromide for 24 hours. Then the ROS level in the cells was detected by 2′,7′-Dichlorodihydrofluorescein diacetate staining and flow cytometry and the protein expressions of NLRP3, ASC, caspase-1, IL-1β, NF-κB and TNF-α determined by Western blot.ResultsThe ROS level was significantly increased in the HK-2 cells treated with iopromide at 37 mgI/ml (4103.89±98.89), 74 mgI/mL (4450.12±108.90), 111 mgI/mL (5050.85±606.76), 148 mgI/mL (6210.57±145.74) and 185 mgI/ml (7105.13±426.63) as compared with that in the control group (2551.71±84.00) (P<0.05). Western blot showed markedly upregulated expressions of NLRP3, ASC, caspase-1, IL-1β and TNF-α in the HK-2 cells in all the latter five groups in comparison with the control (P<0.05) and an increased level of NF-κB after treated with iopromide at ≥111 mgI/ml (P<0.05).ConclusionIopromide may induce injury to HK-2 cells by activating the ROS-NLRP3 inflammasome signaling pathway.
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AIM To observe the drug pair Baizhu-Fuzi's protection on the breast cancer nude mice with bony metastasis and to explore the mechanism of bone metastasis.METHODS Nude mouse models of breast cancer with bone metastasis were developed through injection of breast cancer cell MDA-MB-231BO into the left ventricle.Nude mice were randomly divided into group A and group B.Group A were subdivided into model group,zoledronic acid group and the drug pair of Baizhu-Fuzi group;and Group B were subdivided into sham-operation group,model group,zoledronic acid group and Baizhu-Fuzi group were subsequently administered with the intervention accordingly.The nude mice in group A had their surviving time and the weight changes observed;and those in group B had the degree of bone metastasis examined.Tartrate resistant acid phosphatase (TRAP) method for quantitative determination of osteoclast in bone metastasis,and ELISA method were employed to check the content of TGF-β1 and PTHrP in serum.RESULTS Compared to the model group,Baizhu-Fuzi group displayed distinctly longer survival time (P ＜ 0.05),reduced rate of weight loss 6 weeks after modeling (P ＜ 0.05),significantly declined degree of bone metastasis (P ＜ 0.01),and significantly decreased quantity of TRAP (+) cell (P ＜ 0.05) and serum TGF-β1 and PTHrP (P ＜ 0.05).CONCLUSION The drug pair,Baizhu-Fuzi's influence in TGFβ signal path control and PTHrP expression reduction may contribute to the weight loss management,prolonged survival time,osteolytic bone defect rectification in mouse models of breast cancer with bone metastasis.
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<p><b>OBJECTIVE</b>To explore the inhibitory effect of 2- (4-morpholine) -8- phenyl -4 hydrogen -1- benzo -4 ketone (LY294002) on proliferation of multiple myeloma cell U266 and its mechanism.</p><p><b>METHODS</b>U266 cells were cultured with 0, 5, 10, 20 µmol/L LY294002 for 24, 48 and 72 h, the cell viability was measured by MTT method, cell morphology was observed by acridine orange staining, cell cycle was measured by flow cytometry. The expressions of B-cell lymphoma-2 (BCL-2), BCL-2-associated X protein (BAX), Cyclin D1, Cyclin E and activation of phosphatidyl inositol 3 kinase (PI3K)/protein kinase B (AKT) signal pathway were measured by Western blot.</p><p><b>RESULTS</b>U266 cell viability was reduced in time- and dose-dependent manner after treatment with 5, 10, 20 µmol/L of LY294002 for 24, 48, 72 h. The 5, 10, 20 µmol/L LY294002 leaded to cell nucleus dense and thick, and the cell cycle arrested in the Gphase (P<0.01). The expressions of BCL-2, Cyclin D1, Cyclin E, PI3K and p-AKT were down-regulated (P<0.01), and the expression of BAX up-regulated (P<0.01).</p><p><b>CONCLUSION</b>LY294002 can inhibit U266 cell proliferation via suppresion of activation of PI3K/AKT signal pathway.</p>
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AIM:To study the expression of microRNA (miRNA)-181a in different human lung adenocarcinoma cell lines, and to investigate the effect of miRNA-181a on cell function and its mechanism in human lung adenocarcinoma drug resistant cell A549/DDP.METHODS:Real-time PCR was used to detect the expression of miRNA-181a in BEAS-2B cells, A549 cells and A549/DDP cells.The A549/DDP cells were transfected with pGenesil-miRNA-181a eukaryotic ex-pression plasmid.At the same time, the untransfection group and negative transfection group were also set up .The expres-sion of miRNA-181a, cell viability, cell growth inhibition and apoptosis rate during cis-diamminedichloroplatinum ( DDP) treatment, cell cycle, cell invasion, the protein expression of miRNA-181a target genes bcl-2 and p53 in the A549/DDP cells were determined by real-time fluorescence quantitative PCR , MTT assay, flow cytometry, Transwell method and West-ern blot, respectivly.RESULTS:The expression of miRNA-181a in A549 cells and A549/DDP cells was significantly lower than that in BEAS-2B cells, and the lowest expression level was observed in A 549/DDP cells (P<0.05).The expression of miRNA-181a in A549/DDP cells was significantly increased after transfection with pGenesil-miRNA-181a (P<0.05).The cell viability, cell cycle and invasion ability of the A549/DDP cells were inhibited after miRNA-181a transfection (P <0.05).The cell growth inhibition rate and apoptotic rate of the A 549/DDP cells were increased (P<0.05).The expression of Bcl-2 was reduced, but the expression of P53 was increased after transfection with miRNA-181a in A549/DDP cells (P<0.05).CONCLUSION: miRNA-181a may be correlated with the development of human lung adenocarcinoma .miRNA-181a can serve as a new target for treatment of lung cancer .
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Objective:To probe the therapeutic effect and the mechanism of Jiannao Fuzhi Oral Liquid for treatment of vascular dementia(VD).Methods:Fifty cases conformed with the diagnostic criteria of VD,aged 45～80 years were randomly divided into a treatment group and a control group.The treatment group were treated with oral administration of Jiannao Fuzhi Oral Liquid and the control group with Duxil.MMSE score,BBS score,TCM syndrome indexes before and 1,2,3 months after treatment were detected,and transcracial Doppler's detection(TCD) was carried out before and 3 months after treatment ,and the results were analyzed.Results:There were significant differences in MMSE score,BBS score,TCM syndrome indexes and TCD before and after treatment in both groups.Conclusion:Jiannao Fuzhi Oral Liquid has definite therapeutic effect on VD.