RESUMO
AIM: of the study: This study used network pharmacology and the Gene Expression Omnibus (GEO) database to investigate the therapeutic effects of Corbrin capsules on acute kidney injury (AKI)-COVID-19 (coronavirus disease 2019). MATERIALS AND METHODS: The active constituents and specific molecular targets of Corbrin capsules were obtained from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) and Swiss Target Prediction databases. The targets related to AKI and COVID-19 disease were obtained from the Online Mendelian Inheritance in Man (OMIM), GeneCards, and GEO databases. A protein-protein interaction (PPI) network was constructed by utilizing Cytoscape. To enhance the analysis of pathways associated with the pathogenesis of AKI-COVID-19, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed. Furthermore, immune infiltration analysis was performed by using single-sample gene set enrichment analysis (ssGSEA) and CIBERSORT. Molecular docking was used to assess interactions between differentially expressed genes and active ingredients. Verification was performed by utilizing GEO databases and in vivo assays. RESULTS: This study revealed an overlap of 18 significantly differentially expressed genes between the Corbrin capsules group and the AKI-COVID-19 target group. Analysis of the PPI network identified TP53, JAK2, PIK3CA, PTGS2, KEAP1, and MCL1 as the top six core protein targets with the highest degrees. The results obtained from GO and KEGG analyses demonstrated that the target genes were primarily enriched in the apoptosis and JAK-STAT signaling pathways. Moreover, the analysis of immune infiltration revealed a notable disparity in the percentage of quiescent memory CD4 + T cells. Western blot analyses provided compelling evidence suggesting that the dysregulation of 6 core protein targets could be effectively reversed by Corbrin capsules. CONCLUSION: This study revealed the key components, targets, and pathways involved in treating AKI-related COVID-19 using Corbrin capsules. This study also provided a new understanding of the molecular mechanisms underlying this treatment.
Assuntos
Injúria Renal Aguda , Tratamento Farmacológico da COVID-19 , Simulação de Acoplamento Molecular , Farmacologia em Rede , Mapas de Interação de Proteínas , Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/genética , Mapas de Interação de Proteínas/efeitos dos fármacos , Humanos , COVID-19/genética , Animais , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Bases de Dados Genéticas , Cápsulas , SARS-CoV-2 , Transdução de Sinais/efeitos dos fármacos , Ratos , Masculino , Ontologia Genética , Medicina Tradicional Chinesa/métodosRESUMO
Non-invasive transcranial direct-current stimulation (tDCS) is a safe ischaemic stroke therapy. Cathodal bilateral tDCS (BtDCS) is a modified tDCS approach established by us recently. Because selenium (Se) plays a crucial role in cerebral ischaemic injury, we investigated whether cathodal BtDCS conferred neuroprotection via regulating Se-dependent signalling in rat cerebral ischaemia-reperfusion (I/R) injury. We first showed that the levels of Se and its transport protein selenoprotein P (SEPP1) were reduced in the rat cortical penumbra following I/R, whereas cathodal BtDCS prevented the reduction of Se and SEPP1. Interestingly, direct-current stimulation (DCS) increased SEPP1 level in cultured astrocytes subjected to oxygen-glucose deprivation reoxygenation (OGD/R) but had no effect on SEPP1 level in OGD/R-insulted neurons, indicating that DCS may increase Se in ischaemic neurons by enhancing the synthesis and secretion of SEPP1 in astrocytes. We then revealed that DCS reduced the number of injured mitochondria in OGD/R-insulted neurons cocultured with astrocytes. DCS and BtDCS prevented the reduction of the mitochondrial quality-control signalling, vesicle-associated membrane protein 2 (VAMP2) and syntaxin-4 (STX4), in OGD/R-insulted neurons cocultured with astrocytes and the ischaemic brain respectively. Under the same experimental conditions, downregulation of SEPP1 blocked DCS- and BtDCS-induced upregulation of VAMP2 and STX4. Finally, we demonstrated that cathodal BtDCS increased Se to reduce infract volume following I/R. Together, the present study uncovered a molecular mechanism by which cathodal BtDCS confers neuroprotection through increasing SEPP1 in astrocytes and subsequent upregulation of SEPP1/VAMP2/STX4 signalling in ischaemic neurons after rat cerebral I/R injury. KEY POINTS: Cathodal bilateral transcranial direct-current stimulation (BtDCS) prevents the reduction of selenium (Se) and selenoprotein P in the ischaemic penumbra. Se plays a crucial role in cerebral ischaemia injury. Direct-current stimulation reduces mitochondria injury and blocks the reduction of vesicle-associated membrane protein 2 (VAMP2) and syntaxin-4 (STX4) in oxygen-glucose deprivation reoxygenation-insulted neurons following coculturing with astrocytes. Cathodal BtDCS regulates Se/VAMP2/STX4 signalling to confer neuroprotection after ischaemia.
Assuntos
Isquemia Encefálica , Traumatismo por Reperfusão , Selênio , Acidente Vascular Cerebral , Estimulação Transcraniana por Corrente Contínua , Ratos , Animais , Isquemia Encefálica/terapia , Isquemia Encefálica/metabolismo , Neuroproteção/fisiologia , Proteína 2 Associada à Membrana da Vesícula , Selenoproteína P , Oxigênio/metabolismo , Traumatismo por Reperfusão/prevenção & controle , Traumatismo por Reperfusão/metabolismo , Glucose/metabolismo , Proteínas Qa-SNARERESUMO
Osteoarthritis is a common joint disease characterized by damage to the joint cartilage that occurs throughout the entire joint tissue. This damage primarily manifests as pain in the affected area. In clinical practice, medication is commonly used to relieve pain, but the treatment's effectiveness is poor and recurrent attacks are likely. Schisandrin B is the most abundant biphenylcyclohexene lignan found in the traditional Chinese medicine Schisandra chinensis, and it possesses various pharmacological effects. This study aims to investigate the protective effect of Schisandrin B on mitochondrial damage in osteoarthritis (C28I2 cells) under an inflammatory environment induced by LPS. Cell proliferation and activity, scratch tests, and LDH release tests are utilized to assess cell growth and migration ability. The immunofluorescence assay was used to detect the expression levels of proliferation and apoptosis proteins. The Western Blot assay was used to detect the expression levels of mitochondrial fusion and division proteins. The JC-1 assay was used to detect changes in mitochondrial membrane potential. The mitochondrial fluorescence probe assay was used to detect mitochondrial activity. Through research, it was found that Schisandrin B promotes the proliferation, growth, and migration of C28I2 cells, reduces apoptosis of C28I2 cells, balances mitochondrial fusion and division, stabilizes mitochondrial membrane potential, and promotes mitochondrial activity in an LPS induced inflammatory environment.
Assuntos
Lignanas , Osteoartrite , Compostos Policíclicos , Humanos , Lipopolissacarídeos , Lignanas/farmacologia , Dor , Ciclo-OctanosRESUMO
Current studies have shown that long-term exposure to fine particulate matter (PM2.5) can aggravate lung injury in asthmatic children. The HMGB1/RAGE pathway may play an important role, but few studies on the HMGB1/RAGE signaling pathway in PM2.5-induced asthma have been performed. Epigallocatechin-3-gallate (EGCG), which has antioxidant, anti-inflammatory and immunomodulatory effects, has not been examined in studies at home and abroad. In this study, we established an animal model of asthma and observed that the lung tissue was damaged, inflammatory cells infiltrated, bronchial wall thickness (WTt) and bronchial smooth muscle thickness (WTm) increased and the HMGB1 and RAGE mRNA and protein expression increased. The asthmatic rats exposed to PM2.5 showed significantly increased lung injury and inflammatory cell infiltration, WTt and WTm further increased, and HMGB1 and RAGE mRNA and protein levels were higher than those in the asthma group. The asthmatic rats exposed to PM2.5 were treated with EGCG, which alleviated the lung injury, reduced the number of inflammatory cells, decreased WTt and WTm, and reduced the expression of HMGB1 and RAGE mRNA and protein. The high-dose group showed more significant effects than the other groups. In conclusion, our results suggest that HMGB1 and RAGE are involved in the pathogenesis of asthma. PM2.5 exposure significantly aggravated airway inflammation injury in asthmatic rats. EGCG can reduce lung injury and airway remodeling in PM2.5-exposed asthmatic rats and has lung protective effects. The mechanism may be related to regulation of the HMGB1/RAGE signaling pathway. Our results may provide new ideas and methods for the prevention and treatment of PM2.5-induced asthma.
Assuntos
Asma/etiologia , Catequina/análogos & derivados , Proteína HMGB1/metabolismo , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Remodelação das Vias Aéreas/efeitos dos fármacos , Animais , Asma/tratamento farmacológico , Catequina/farmacologia , Modelos Animais de Doenças , Inflamação/tratamento farmacológico , Pulmão/patologia , Lesão Pulmonar/tratamento farmacológico , Material Particulado/farmacologia , Ratos , Transdução de Sinais/efeitos dos fármacosRESUMO
BACKGROUND: The aim of this study was to evaluate the clinical value of adjuvant chemobiotherapy via portal vein for patients with hepatocellular carcinoma (HCC) with portal vein tumor thrombi (PVTT) following hepatectomy plus thrombectomy. METHODS: Eighty-six HCC patients with tumor thrombi in the portal trunk and/or the first-order branch were divided into groups A (n = 33) and B (n = 53). Patients in group A were treated with hepatectomy plus portal thrombectomy in combination with postoperative adjuvant chemobiotherapy administered via portal vein. The chemobiotherapy regimen consisted of 5-FU, adriamycin, cisplatin, and IFNalpha. Patients in Group B were subjected to hepatectomy plus thrombectomy alone. Survival rates of the two groups were compared and prognostic factors were identified using Cox proportional hazards model. RESULTS: Group A had a significantly longer median tumor-free survival time and median survival time compared with group B, i.e., 5.1 vs. 2.5 months (p = 0.017) and 11.5 vs. 6.2 months (p = 0.007), respectively. One-, two-, and three-year tumor-free survival rates were remarkably higher in group A than in group B, i.e., 18.4% vs. 8.4%, 13.8% vs. 4.2%, and 9.2% vs. 4.2%, respectively. One-, two-, and three-year survival rates were markedly greater in group A than in group B, i.e., 46.8% vs. 23.4%, 14.4% vs. 5.8%, and 9.6% vs. 5.8%, respectively. Multivariate analysis using the Cox proportional hazards model revealed that adjuvant chemobiotherapy, pathologic grading, and tumor size were independent prognostic factors for survival time (p = 0.000, 0.001, and 0.013, respectively), and chemobiotherapy and pathologic grading were independent prognostic factors for tumor-free survival time (p = 0.002 and 0.003, respectively). CONCLUSIONS: Surgical resection combined with adjuvant chemobiotherapy via portal vein is an effective and safe treatment modality for hepatocellular carcinoma with major portal vein thrombus.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Hepatocelular/terapia , Hepatectomia , Neoplasias Hepáticas/terapia , Trombectomia , Trombose Venosa/cirurgia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Quimioterapia Adjuvante/métodos , Cisplatino/administração & dosagem , Terapia Combinada/métodos , Doxorrubicina/administração & dosagem , Feminino , Fluoruracila/administração & dosagem , Hepatectomia/métodos , Humanos , Interferon alfa-2 , Interferon-alfa/administração & dosagem , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Invasividade Neoplásica , Veia Porta , Proteínas Recombinantes , Fatores de Risco , Taxa de Sobrevida , Trombectomia/métodos , Trombose Venosa/tratamento farmacológico , Trombose Venosa/etiologiaRESUMO
OBJECTIVE: To observe the effect of parenteral nutrition (PN) with branched-chain amino acid supplementation on protein metabolism after partial hepatectomy in rats with liver cirrhosis. METHODS: Eighteen rats with liver cirrhosis were randomly divided into pre-operation group (n=6), post-operation 8.5% Novamin PN group (n=6) and post-operation 10% Hepa PN group (n=6), with 6 normal rats severing as the normal control group. Five days after the operation, serum albumin (ALB), insulin-like growth factor I (IGF-1) and plasma amino acid spectrum were measured, and ALB mRNA level in the liver was assayed using RT-PCR. RESULTS: Postoperative serum ALB was similar between 10% Hepa PN and 8.5% Novamine PN groups, but the rats in the latter group showed significantly increased serum IGF-1 level, Fischer ratio and hepatic ALB mRNA expression (P<0.05). CONCLUSION: Administration of PN with branched-chain amino acid supplementation can ameliorate plasma amino acid spectrum and increase protein synthesis in rats with liver cirrhosis after partial hepatectomy.