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Background: Diabetic kidney disease (DKD) is a severe microvascular complication of diabetes mellitus that can lead to end-stage renal disease. Colquhounia root tablet (CRT) has shown therapeutic potential in treating DKD, but its efficacy and underlying mechanisms remain to be elucidated. Methods: A randomized controlled clinical trial was conducted on 61 DKD patients. The treatment group received CRT in addition to standard therapy, while the control group received standard therapy alone. Treatment efficacy and adverse events were evaluated after 3 months. Additionally, in vitro experiments using human renal tubular epithelial cells (HK-2) were performed to investigate the effect of CRT on high glucose (HG)-induced epithelial-mesenchymal transition (EMT) and the involvement of the PTEN/PI3K/AKT signaling pathway. Results: CRT treatment significantly improved proteinuria and increased the effective treatment rate in DKD patients compared to the control group, with no significant difference in adverse events. Moreover, CRT reversed HG-induced EMT in HK-2 cells, as evidenced by the downregulation of α-SMA and upregulation of E-cadherin at both mRNA and protein levels. Mechanistically, CRT increased PTEN expression and inhibited the PI3K/AKT pathway, similar to the effects of the PI3K inhibitor LY29400. The combination of CRT and LY29400 further enhanced PTEN mRNA expression under HG conditions. Conclusion: CRT effectively improves proteinuria in DKD patients and ameliorates HG-induced EMT in HK-2 cells. The underlying mechanism may involve the upregulation of PTEN and subsequent inhibition of the PI3K/AKT signaling pathway. These findings provide new insights into the therapeutic potential of CRT for DKD treatment.
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Objective: To compare the efficacy of a steroid-free regimen with steroid-based treatment in managing primary membranous nephropathy (PMN) and investigate the potential benefits of steroid-free regimens in PMN therapy. Methods: This was a single-centre prospective cohort study. A total of 81 patients were divided into two groups according to their medication regimen: a rituximab (RTX)/tacrolimus (TAC) group (low-dose RTX combined with low-dose TAC group, without steroids, n = 31) and a prednisone (P)/TAC group (P combined with TAC group, n = 61). The changes in 24-h urine protein quantification, levels of blood albumin, blood creatinine, total cholesterol, triglyceride and fasting blood glucose as well as anti-phospholipase A2 receptor antibody titres were observed in both groups before treatment and after 1, 3, 6 and 12 months of treatment. Clinical remission (complete and partial remission), serological remission and recurrence were assessed in both groups after treatment, and the occurrence of adverse reactions was observed. Results: 1) Before treatment, there was no significant difference in baseline values between the two groups (p > 0.05). 2) After 12 months of treatment, the 24-h proteinuria and total cholesterol levels in the RTX/TAC group were significantly lower than those in the P/TAC group (p < 0.05). 3) After 6 months of treatment, the clinical remission rate of the RTX/TAC group was significantly higher than that of the P/TAC group (p < 0.05). After 12 months of treatment, the clinical remission rate of the RTX/TAC group was significantly higher than that of the P/TAC group (p < 0.05). (4) After 3, 6 and 12 months of treatment, serological remission rates in the RTX/TAC group were significantly higher than those in the P/TAC group (p < 0.05). During treatment, the anti-PLA2R antibody titres in the RTX/TAC group remained lower than those in the P/TAC group (p < 0.05). Conclusion: The low-dose RTX combined with low-dose TAC steroid-free regimen induces serological remission in patients with PMN earlier than the classic regimen of P combined with TAC, and there was no significant difference in adverse effects between the two groups. Besides, the long-term clinical remission effect of low-dose RTX combined with low-dose TAC is better than that of P combined with TAC.
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OBJECTIVE: To investigate the changes in Treg and Th17 cells and explore the significance of Treg/Th17 balance in adult primary membranous nephropathy (PMN) patients. MATERIALS AND METHODS: A total of 60 PMN patients and 50 healthy adults from June 2013 to October 2016 were enrolled in this study. The levels of Treg, Th17, and related cytokines were assessed. Pearson correlation was used for conducting correlation analysis. RESULTS: There was a significant increase in Th17 frequencies and IL-17 (Th17-related cytokines) in the peripheral blood mononuclear cells (PBMCs), as well as a significant decrease in Treg frequencies and IL-10 (Treg-related cytokines). The IL-17 concentrations in the peripheral blood of PMN patients were positively correlated with urinary protein, while IL-10 levels were negatively correlated with urinary protein. Protein expression of Treg transcription factor (Foxp3) was significantly low in the renal tissues of PMN patients, while the expression of IL-17 was much higher. Th17/Treg imbalance was reversed to normal after effective treatment with tacrolimus in 15 PMN patients. CONCLUSION: These results suggested the existence of Treg/Th17 imbalance in PMN patients, showing the importance of Treg/Th17 imbalance in PMN pathogenesis.
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Glomerulonefritis Membranosa , Células Th17 , Adulto , Citocinas , Factores de Transcripción Forkhead , Glomerulonefritis Membranosa/diagnóstico , Glomerulonefritis Membranosa/tratamiento farmacológico , Humanos , Leucocitos Mononucleares , Linfocitos T ReguladoresRESUMEN
BACKGROUND: Actin filament-associated protein 1-antisense RNA 1 (AFAP1-AS1) plays an important role in the development and progression of several human cancers. However, its biological function in gastric cancer (GC) progression is still unknown. METHODS: We used qRT-PCR to detect the relative expression of AFAP1-AS1 in GC tissues and cell lines. The loss-of-function assays were conducted to detect the effect of AFAP1-AS1 on GC development. Bioinformatics analysis, luciferase reporter gene analysis, and RIP analysis were used to identify and validate target genes of AFAP1-AS1. Finally, rescue tests were performed to confirm the influence of the AFAP1-AS1-miR-155-5p-FGF7 axis on GC development. RESULTS: AFAP1-AS1 was upregulated in GC tissues and cell lines and was closely correlated with poor prognosis of GC patients. AFAP1-AS1 knockdown inhibited proliferation, migration, and invasion of GC cells, indicating that AFAP1-AS1 acts as an oncogene in GC. Bioinformatics analysis, dual-luciferase reporter gene detection, and RIP assays validated that AFAP1-AS1 directly interacts to miR-155-5p and could positively affect cell proliferation, migration, and invasion by regulation of the expression of miR-155-5p and FGF7. Further rescue assays revealed that AFAP1-AS1 promotes cell proliferation and metastasis through the miR-155-5p/FGF7 axis in GC. CONCLUSIONS: AFAP1-AS1 might be an oncogenic lncRNA that promoted GC progression by acting as a competing endogenous RNA (ceRNA) that regulates the expression of FGF7 through sponging miR-155-5p, suggesting that AFAP1-AS1 may be a novel potential therapeutic target for GC.
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Factor 7 de Crecimiento de Fibroblastos/genética , MicroARNs/genética , ARN Largo no Codificante/genética , Neoplasias Gástricas/patología , Regiones no Traducidas 3' , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Progresión de la Enfermedad , Femenino , Factor 7 de Crecimiento de Fibroblastos/metabolismo , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Invasividad Neoplásica , Pronóstico , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Regulación hacia ArribaRESUMEN
Calcific aortic valve disease (CAVD) is the most common heart valve disorder in human populations. Nevertheless, there are presently no effective means for its prevention and treatment. It is therefore critical to comprehensively define key mechanisms of the disease. A major focus of cardiovascular research has been characterization of how regulation of gene expression maintains healthy physiologic status of the component tissues of the system and how derangements of gene regulation may become pathological. Recently, substantial evidence has emerged that noncoding RNAs, which are an enormous and versatile class of regulatory elements, such as microRNAs and long noncoding RNAs, have roles in onset and prognosis of CAVD. Authors of the present report have therefore here provided a summary of the current understanding of contributions made by noncoding RNAs major features of CAVD. It is anticipated that this article will serve as a valuable guide to research strategy in this field and may additionally provide both researchers and clinicians with an expanded range of CAVD-associated biomarkers.
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Estenosis de la Válvula Aórtica/genética , Válvula Aórtica/metabolismo , Válvula Aórtica/patología , Calcinosis/genética , ARN no Traducido/genética , Animales , Estenosis de la Válvula Aórtica/metabolismo , Estenosis de la Válvula Aórtica/patología , Calcinosis/metabolismo , Calcinosis/patología , Regulación de la Expresión Génica , Marcadores Genéticos , Terapia Genética/métodos , Humanos , Valor Predictivo de las Pruebas , ARN no Traducido/metabolismo , ARN no Traducido/uso terapéutico , Transducción de SeñalRESUMEN
BACKGROUND AND AIMS: The safety of propofol sedation during colonoscopy remains unclear, and we performed a meta-analysis to assess the risk of perforation in patients undergoing propofol vs. traditional sedation. METHODS: MEDLINE, CBM, VIP, CNKI, and Wanfang databases were searched up to December 2016. Two reviewers independently assessed abstract of those searched articles. Data about perforation condition in propofol and traditional sedation groups were extracted and combined using the random effects model. RESULTS: A total of 19 studies were included in the current meta-analysis. Compared to traditional sedation, propofol sedation did not increase the risk of perforation (RD = - 0.00, 95% CI - 0.00~0.00, p = 0.98; subgroup analysis: OR = 1.30, 95% CI 0.83~2.05, p = 0.25). CONCLUSION: This meta-analysis suggested that propofol sedation did not increase the risk of perforation compared to traditional sedation during colonoscopy.
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Colonoscopía , Sedación Consciente/métodos , Perforación Intestinal/etiología , Propofol , Colonoscopía/efectos adversos , Sedación Consciente/efectos adversos , Bases de Datos Bibliográficas , Humanos , Perforación Intestinal/epidemiología , RiesgoRESUMEN
Aberrant expression of microRNAs (miRNAs) plays an important role in gastric cancer (GC) development. miR-93-5p has shown opposing functions in different types of cancers, but the exact expression pattern and molecular mechanism of miR-93-5p in GC development remain to be elucidated. Here, we reported that miR-93-5p expression was increased in GC tissues compared with the adjacent normal tissues and that its overexpression was correlated with distant metastasis and poor survival in GC patients. miR-93-5p knockdown inhibited the migration, invasion and proliferation of GC cells in vitro and in vivo, while its overexpression displayed an opposite result. Using an mRNA microarray, we found that miR-93-5p significantly downregulated IFNAR1 expression in GC cells, which was further identified as a direct target of miR-93-5p. IFNAR1 knockdown promoted GC cell migration and invasion, but its restoration could rescue GC cell migration and invasion induced by miR-93-5p overexpression. Moreover, miR-93-5p-IFNAR1 axis increased MMP9 expression via STAT3 pathway in GC cells. Taken together, we reveal that miR-93-5p overexpression is associated with the poor survival of GC patients and miR-93-5p-IFNAR1 axis promotes GC metastasis through activation of STAT3 pathway.
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Regulación Neoplásica de la Expresión Génica , MicroARNs/genética , Neoplasias Peritoneales/secundario , Receptor de Interferón alfa y beta/metabolismo , Factor de Transcripción STAT3/metabolismo , Neoplasias Gástricas/patología , Animales , Apoptosis , Movimiento Celular , Proliferación Celular , Femenino , Humanos , Metástasis Linfática , Masculino , Ratones , Ratones Desnudos , Persona de Mediana Edad , Invasividad Neoplásica , Neoplasias Peritoneales/genética , Neoplasias Peritoneales/metabolismo , Pronóstico , Receptor de Interferón alfa y beta/genética , Factor de Transcripción STAT3/genética , Transducción de Señal , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Tasa de Supervivencia , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
AIM: To investigate the effect of low-dosage steroid therapy in patients with severe aristolochic acid nephropathy (AAN). METHODS: Forty-three chronic AAN patients in the Peking Union Medical College Hospital and the First Affiliated Hospital of Xinxiang Medical College were included in this study from November 1998 to October 2013. According to the treatment method, the patients were divided into a steroid group (SG, n = 25) and a control group (CG, n = 18). The serum biochemical indicators at the basement in the two groups exhibited no obvious statistical differences. In comparison with the baseline data, the levels of serum creatinine at 3, 6, 9, and 12 months were analyzed. The blood pressure, haemoglobin, serum biochemical indicators, and the side-effects of steroid application were also observed. Urinary macrophage chemoattractant protein-1 (MCP-1) and transforming growth factor-1 (TGF-1) amounts were measured as well. RESULTS: (i) The serum creatinine content in the CG group was significantly higher than the baseline level during the follow-up(6, 9, and 12 months later), whereas in the SG group it decreased during the 3-6 month period and remained stable within 1 year. (ii) The biochemical indicators, blood pressure, and haemoglobin persisted stable. (iii) The side-effects of low-dosage steroid therapy were not severe and were tolerated by the AAN patients. (4) Urinary MCP-1 and TGF-1 concentrations were positively correlated with serum creatinine and decreased in the SG group. CONCLUSION: Low-dosage steroid therapy reversed or delayed the renal failure progression in severe chronic AAN patients, which may be associated with the suppression of MCP-1 and TGF-ß1 activities.
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Ácidos Aristolóquicos/efectos adversos , Glucocorticoides , Fallo Renal Crónico , Anciano , Factores Quimiotácticos/sangre , China , Creatinina/sangre , Progresión de la Enfermedad , Relación Dosis-Respuesta a Droga , Monitoreo de Drogas/métodos , Femenino , Estudios de Seguimiento , Glucocorticoides/administración & dosificación , Glucocorticoides/efectos adversos , Humanos , Fallo Renal Crónico/sangre , Fallo Renal Crónico/inducido químicamente , Fallo Renal Crónico/diagnóstico , Fallo Renal Crónico/tratamiento farmacológico , Pruebas de Función Renal/métodos , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Estadística como Asunto , Factor de Crecimiento Transformador beta1/sangre , Resultado del TratamientoRESUMEN
The geographical origin traceability of food, an important part of traceability system, is effective in protecting the quality and safety of foodstuffs. Near-infrared spectroscopy (NIR), which is a powerful technique for geographical origin traceability, has attracted extensive attention by scientists due to its speediness, non-pollution and simple operation. This paper presents the advantages and disadvantages of techniques that have been used for food geographical origin traceability. The basic principles of NIR and its applications in different food geographical origin traceability are presented too. Furthermore, problems in applications are analyzed and the future development trends are discussed.