Comparison of the efficacy of steroid-free versus classic steroid-containing regimens in primary membranous nephropathy.

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.

Changes and significance of Treg and Th17 in adult patients with primary membranous nephropathy.

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.

Long Noncoding RNA AFAP1-AS1 Promotes Cell Proliferation and Metastasis via the miR-155-5p/FGF7 Axis and Predicts Poor Prognosis in Gastric Cancer.

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.

Noncoding RNAs in Calcific Aortic Valve Disease: A Review of Recent Studies.

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.

miR-93-5p/IFNAR1 axis promotes gastric cancer metastasis through activating the STAT3 signaling pathway.

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.

Influence and analysis of low-dosage steroid therapy in severe aristolochic acid nephropathy patients.

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.

FTY720 enhances chemosensitivity of colon cancer cells to doxorubicin and etoposide via the modulation of P-glycoprotein and multidrug resistance protein 1.

OBJECTIVE: This study aimed to investigate the effects of FTY720 on inducing cell growth inhibition and enhancing the cytotoxicity of anti-cancer drugs in the human colon cancer cell line HCT-8 and its multidrug-resistant cell line HCT-8/5-fluorouracil (HCT-8/5-Fu). METHODS: Cell viability and apoptosis after being treated with FTY720 alone or in combination with doxorubicin (DOX) and etoposide (VP16) were tested in HCT-8 and HCT-8/5-Fu cells. The changes in P-glycoprotein (P-gp) and multidrug resistance protein 1 (MRP1) were determined at the mRNA and functional levels. RESULTS: FTY720 showed anti-proliferative activity against cancer cells in a dose-dependent and time-dependent manner and could enhance the cytotoxicity of DOX and VP16 in both HCT-8 and HCT-8/5-Fu cell lines. In addition, treatment with FTY720 resulted in the promotion of VP16-induced cell apoptosis and an increased accumulation of intracellular DOX and two specific fluorescent substrates of P-gp and MRP1 through the inhibition of efflux and the suppression of gene expression. CONCLUSION: FTY720 exerts its chemosensitization effect in HCT-8 and HCT-8/5-Fu cell lines by promoting cell apoptosis and inhibiting P-gp and MRP1, which could be applied as a potential co-adjuvant therapeutic modality.

[Current progress in food geographical origin traceability by near infrared spectroscopy technology].

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.