Evaluating Efficacy and Safety of Tacrolimus Treatment in Membranous Nephropathy: Results of a Retrospective Study of 182 Patients.

Purpose: Tacrolimus is recommended by KDIGO Clinical Practice Guidelines as an initial therapy for the treatment of membranous nephropathy (MN). However, little is known about the factors that influence response and recurrence of the disease after tacrolimus therapy, and there are limited data regarding the duration of tacrolimus treatment. Here, we present a real-world retrospective cohort study of 182 MN patients treated with tacrolimus, aiming to assess the efficacy and safety of tacrolimus in the treatment of MN. Patients and Methods: The clinical data of 182 patients with MN treated with tacrolimus and followed up for at least one year were analyzed retrospectively for the efficacy and safety of tacrolimus. Results: The mean follow-up period was 27.3 (19.3-41.6) months. A total of 154 patients (84.6%) achieved complete or partial remission, and 28 patients (15.4%) did not. Multivariate Cox regression analysis showed that male and higher baseline BMI were independently associated with lower, while higher serum albumin was associated with higher probability of remission. Among the responders, 56 patients (36.4%) relapsed. After adjustments for age and sex, Cox regression analysis revealed that the longer period of full-dose tacrolimus was administered, the lower the incidence of relapse. However, high levels of serum creatinine and proteinuria at the onset of tacrolimus discontinuation were risk factors for relapse. During the treatment of tacrolimus, a decline in renal function (≥50% increase in serum creatinine after the onset of tacrolimus treatment) was the most common adverse reaction, observed in 20 (11.0%) patients, followed by elevated blood glucose and infection, but the latter two occurred mostly during treatment with tacrolimus plus corticosteroids. Conclusion: Tacrolimus is effective in the treatment of MN, but the relapse rate is high. Clinical studies with larger sample sizes are needed to further explore the use of tacrolimus in the treatment of membranous nephropathy.

Serum uric acid is not associated with major depressive disorder in European and South American populations: a meta-analysis and two-sample bidirectional Mendelian Randomization study.

OBJECTIVE: Although previous epidemiological studies have demonstrated that serum uric acid (SUA) is associated with major depressive disorder (MDD), these analyses are prone to biases. Here, we applied the Mendelian Randomization approach to determine whether SUA is causally associated with MDD. METHODS: We conducted a meta-analysis to evaluate the relationship between SUA and MDD, then applied summary data from the Global Urate Genetics Consortium and the Psychiatric Genomics Consortium to estimate their causal effect using a two-sample bidirectional Mendelian Randomization (MR) analysis. Thereafter, the causal effect was further researched using genetic risk scores (GRS) as instrumental variables (IVs). RESULTS: Results of a meta-analysis of articles comprising 6975 and 13,589 MDD patients and controls, respectively, revealed that SUA was associated with MDD (SMD = -0.690, 95% CI: -0.930 to -0.440, I2 = 97.4%, P < 0.001). In addition, the five MR methods revealed no causal relationship existed between SUA and MDD, which corroborated the results obtained via the GRS approach. CONCLUSION: This paper found little evidence that this association between SUA and MDD is casual. Genetically, there was no significant causal association between SUA and MDD.

Up-regulation of MARVEL domain-containing protein 1 (MARVELD1) accelerated the malignant phenotype of glioma cancer cells via mediating JAK/STAT signaling pathway.

This work aimed to research the function of MARVEL domain-containing protein 1 (MARVELD1) in glioma as well as its functioning mode. Bioinformatics analysis was utilized to assess the MARVELD1 expression in glioma tissues and its relationship with grade and prognosis, based on The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Chinese Glioma Genome Atlas (CGGA) databases. Cell Counting Kit-8 (CCK-8), colony formation, and Transwell assays were carried out to determine the impact of MARVELD1 on malignant biological behavior of glioma, such as proliferation, invasion, and migration. qRT-PCR was carried out to test the mRNA level of MARVELD1. Western blot assay was performed to measure the protein expression of MARVELD1 and JAK/STAT pathway-related proteins. MARVELD1 was expressed at high levels in glioma tissues and cell lines. Kaplan-Meier survival analysis revealed that the higher MARVELD1 expression, the shorter the survival time of patients with glioma. Also, the MARVELD1 expression in WHO IV was significantly enhanced compared to that in WHO II and WHO III. Furthermore, the functional analysis of MARVELD1 in vitro revealed that knockdown of MARVELD1 in U251 cells restrained cell proliferation, migration, and invasion, while up-regulation of MARVELD1 in U87 cells presented opposite outcomes. Finally, we found that JAK/STAT signaling pathway mediated the function of MARVELD1 in glioma. MARVELD1 contributed to promoting the malignant progression of glioma, which is the key driver of activation of JAK/STAT signaling pathway in gliomas.

Up-regulation of MARVEL domain-containing protein 1 (MARVELD1) accelerated the malignant phenotype of glioma cancer cells via mediating JAK/STAT signaling pathway

This work aimed to research the function of MARVEL domain-containing protein 1 (MARVELD1) in glioma as well as its functioning mode. Bioinformatics analysis was utilized to assess the MARVELD1 expression in glioma tissues and its relationship with grade and prognosis, based on The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Chinese Glioma Genome Atlas (CGGA) databases. Cell Counting Kit-8 (CCK-8), colony formation, and Transwell assays were carried out to determine the impact of MARVELD1 on malignant biological behavior of glioma, such as proliferation, invasion, and migration. qRT-PCR was carried out to test the mRNA level of MARVELD1. Western blot assay was performed to measure the protein expression of MARVELD1 and JAK/STAT pathway-related proteins. MARVELD1 was expressed at high levels in glioma tissues and cell lines. Kaplan-Meier survival analysis revealed that the higher MARVELD1 expression, the shorter the survival time of patients with glioma. Also, the MARVELD1 expression in WHO IV was significantly enhanced compared to that in WHO II and WHO III. Furthermore, the functional analysis of MARVELD1 in vitro revealed that knockdown of MARVELD1 in U251 cells restrained cell proliferation, migration, and invasion, while up-regulation of MARVELD1 in U87 cells presented opposite outcomes. Finally, we found that JAK/STAT signaling pathway mediated the function of MARVELD1 in glioma. MARVELD1 contributed to promoting the malignant progression of glioma, which is the key driver of activation of JAK/STAT signaling pathway in gliomas.