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Objective: To investigate the therapeutic effect and mechanism of lenvatinib on regorafenib-resistant hepatocellular carcinoma cells. Methods: CCK-8 and clone formation assay were used to observe the inhibitory effect of lenvatinib on the growth of hepatocellular carcinoma cells. Flow cytometry was used to detect the apoptosis of regorafenib-resistant hepatocellular carcinoma cells treated with lenvatinib. The expression levels of related proteins were detected by western blot and immunohistochemical staining. The inhibitory effect of lenvatinib on the tumor formation ability of regorafenib-resistant hepatocellular carcinoma cells in vivo was observed by subcutaneous tumor formation experiment in mice. Results: CCK-8 and clone formation assay showed that lenvatinib could inhibit the proliferation of regorafenib-resistant hepatocellular carcinoma cells. The number of clones of HepG2, SMMC7721 and regorafenib-resistant HepG2, SMMC7721 cells in lenvatinib group (120.67±11.06, 53.00±11.14, 55.00±9.54, 78.67±14.64) were all lower than those in control group (478.00±24.52, 566.00±27.87, 333.67±7.02, 210.00±12.77, all P<0.05). Flow cytometry showed that lenvatinib could promote apoptosis of regorafenib-resistant hepatocellular carcinoma cells, the apoptosis rates of HepG2, SMMC7721 and regorafenib-resistant HepG2, SMMC7721 cells in lenvatinib group [(12.30±0.70)%, (9.83±0.38)%, (15.90±1.32)%, (10.60±0.00)%] were all higher than those in control group [(7.50±0.87)%, (5.00±1.21)%, (8.10±1.61)%, (7.05±0.78)%, all P<0.05]. The apoptosis-related protein levels suggested that apoptosis was increased in the treatment of lenvatinib. The animal study showed that lenvatinib can inhibit the growth of regorafenib-resistant cells in vivo. Immunohistochemistry and western blot results showed that lenvatinib could down-regulate the abnormally activated IGF1R/Mek/Erk signaling pathway in regorafenib-resistant cells. Conclusion: Lenvatinib can reverse regorafenib resistance in hepatocellular carcinoma, possibly by down-regulating IGF1R/Mek/Erk signaling pathway.
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Animals , Mice , Humans , Apoptosis , Carcinoma, Hepatocellular/pathology , Cell Line, Tumor , Cell Proliferation , Liver Neoplasms/pathology , Signal TransductionABSTRACT
This study used nasal lavage fluid for metabolomics to explore its feasibility, and applied it to the clinical metabolomics study of Xiaoqinglong Decoction in the treatment of allergic rhinitis(AR), aiming to investigate the molecular mechanism of Xiaoqing-long Decoction in the treatment of AR through differential changes in local nasal metabolism. AR patients were selected as the research subjects, and nasal lavage fluid was collected as the sample. Metabolomics analysis using liquid chromatography-mass spectrometry was performed on normal group, AR group, and Xiaoqinglong Decoction group. The differences in metabolic profiles among the groups were compared using principal component analysis and partial least squares discriminant analysis, and differential metabolites were identified and subjected to corresponding metabolic pathway analysis. The results showed that Xiaoqinglong Decoction significantly improved the symptoms of AR patients. The metabolomics analysis revealed 20 differential metabolites between AR group and Xiaoqinglong Decoction group. The core metabolite with a trending return in comparison to normal group was trimethyladipic acid. The metabolites were involved in multiple pathways, including β-alanine metabolism, glutathione metabolism, and phenylalanine, tyrosine, and tryptophan biosynthesis. The feasibility of applying nasal lavage fluid in nasal metabolomics was preliminarily demonstrated. Differential metabolites and enriched pathways in the treatment of AR patients with Xiaoqinglong Decoction were identified, indicating that it may improve rhinitis symptoms through the regulation of various metabolites, including antioxidant effects and correction of Th1/Th2 imbalance.
Subject(s)
Humans , Nasal Lavage Fluid , Rhinitis, Allergic/drug therapy , Metabolomics/methods , MetabolomeABSTRACT
Objective: To investigate the therapeutic effect and related mechanism of Shenling Baizhu San on 3% dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) mice. Method: Sixty male SPF C57BL/6 mice were randomly divided into control group, salazosulfapyridine (SASP, 0.52 g·kg-1), and low, medium and high-dose (31.2, 15.6, 7.8 g·kg-1) Shenling Baizhu San groups. Except for the control group, mice in the other groups were given distilled water containing 3% dextran sulfate sodium salt for a week to establish UC models. The drug was administered once a day for 14 days. The normal group and the model group were administered with 0.9%physiological saline at 20 mL·kg-1. The mice's body weight, fecal traits, and occult blood were observed daily, and the disease activity index (DAI) was scored. After the end of the administration, the blood was collected, mice colons were collected, weighed and measured for length, and pathological sections were prepared. Enzyme-linked immunosorbent assay (ELISA) kit was used to detect the serum levels of interleukin-18 (IL-18) and IL-1β in mice; htoxylin eosin (HE) and alixin blue/schiff periodic acid shiff(AB/PAS) staining were used to observe the pathological changes of colon tissues; Western blot was used to detect the colon tissue of mice nucleotide binding oligomerization domain-like receptor 3 (NLPR3), NLPR6 protein expression levels. Result: Compared with the normal group, the DAI score of the model group was increased (PPβ content increased (PPPβ concentration was decreased (PPPPConclusion: Shenling Baizhu San has the effect in treating DSS-induced UC mice, which may be related to the regulation of NLRP3, NLRP6 protein and related inflammatory factors, so as to reduce intestinal inflammation and alleviate intestinal mucosal damage.
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AIM: To comparatively analyze the application of laser confocal microscopy and corneal smear in the diagnosis of fungal keratitis.METHODS: Totally 77 patients (77 eyes) diagnosed as fungal keratitis were selected.Laser confocal microscopy and corneal smear examination were performed to observe the characteristics of the images, and the detection rate of fungus were compared between the two methods.RESULTS: Of the 77 patients, 66 eyes (86%) were positive and 11 eyes were negative detected by laser confocal microscopy;51 eyes (66%) were positive and 26 eyes were negative detected by corneal smear examination, the difference was statistically significant compared between two group (P<0.05).CONCLUSION: Laser corneal confocal microscopy is relatively safe and sensitive.If combined the application of laser corneal confocal microscopy and corneal smear examination in clinical, the diagnosis rate of fungal keratitis may be improved.
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<p><b>OBJECTIVE</b>To investigate the prevalence, etiology and clinical characteristics of adrenal lesions detected by abdominal computed tomography (CT).</p><p><b>METHODS</b>This retrospective study was conducted in patients with adrenal lesions detected by abdominal CT examinations in Nanfang Hospital between July, 2014 and June, 2015. The clinical data of the patients were collected for analysis of the demographics, comorbidities, imaging characteristics, biochemical profiles, clinical diagnosis and intervention.</p><p><b>RESULTS</b>A total of 939 patients with adrenal lesions were identified from 19 004 patients undergoing abdominal CT scan over the defined period. The mean age of the patients was 53.2 years and 560 of the patients were male. Among the total cases with adrenal lesions, the percentages of cases with adrenal masses tended to increase progressively with age. Endocrine studies were done in 270 of the total patients, which identified non-functioning masses in 38.9%, primary aldosteronism in 16.3%, Cushing's syndrome in 4.1%, subclinical Cushing's syndrome in 7.0%, and pheochromocytomas in 7.0% of the cases. Adrenal incidentalomas was detected in 191 patients, with a detection rate of 1.0% among the overall patients undergoing abdominal CT scans. Imaging study detected adenomas (70.3%), cortical carcinomas (2.4%), and metastases (0.5%). Of 191 patients with adrenal incidentalomas, only 76 (39.8%) underwent endocrine evaluation, including 34 with nonfunctioning adrenal masses, 17 with pheochromocytoma, 7 with primary aldosteronism, and 5 with subclinical Cushing's syndrome.</p><p><b>CONCLUSION</b>s The overall detection rates of adrenal lesions and adrenal incidentalomas by abdominal CT were 4.9% and 1.0%, respectively, in our cohort of patients undergoing the examination over the defined period. Although most of the lesions were benign and nonfunctioning, malignant and functional lesions were also detected. As many as 60% of the patients with adrenal incidentalomas did not have hormonal testing. Clinicians need to have greater awareness of adrenal incidentalomas and standard protocol for its management should be established.</p>
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AIM: To discuss the protective effects and possible mechanisms of quercetin in oxidative damage of human retina pigment epithelium ( RPE) cells induced by H2 O2 .METHODS: RPE cells were subculture, and they were divided into negative control group: cultured with normal culture medium;oxidative injury group:100 μmol/L H2 O2 treated for 12h; quercetin low dose group: 100 μmol/L quercetin incubated for 24h then treated with 100 μmol/L H2 O2 for 12h; and quercetin high dose group:100 μmol/L quercetin incubated for 24h then treated with 100 μmol/L H2 O2 for 12h. Cell viability were tested by MTT colorimetric detection, apoptosis rate was detected by flow cytometry, apoptotic cell morphology was observed by Hochest33258 staining, expression of catalase (CAT), superoxide dismutase ( SOD) and glutathione peroxidase ( GSH-Px) were tested by colorimetric detection. RESULTS: Quercetin inhibited H2 O2 - induced cell viability decreased in RPE cells, after treated with different concentrations of quercetin, RPE cells activity increased to (79. 67±4. 98)% and (83. 00±3. 60)%, which had statistical significance difference compared with oxidative damage group (48. 93±3. 39)% (P CONCLUSION:Quercetin effectively inhibited H2 O2 -induced RPE cells damage by improving cell antioxidant enzyme activity, which provide reliable experimental basis for the treatment of injuries in RPE cells.
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Objective Application of the second metatarpophalangeal joint by traction prolong trans- plant repair the defects in the metacarpophalangeal joint,reconstruct the function of it.Methods By means of the apparatus to prolong finger in advance,then transplant the second metatarpophalangeal joint to recon- struct metacarpophalangeal joint for seven cases of obsolete defects in the metacarpophalangeal joint.Results The average of finger prolong was 2.6 cm,consultation from 1 to 4 years.average 2.5 years,thai the trans- plant joints have all survived and osteal concrescence.Through the criterion Chinese Medical Association,good rate was 85.7%. Conclusion It' s a good method to repair obsolete defects in the metacarpophalangeal joint by transplant traction prolong of the second metatarpophalangeal joint.