[Alteration and significance of serum lipid levels and nutritional status during BCMA-CAR-T-cell therapy in patients with refractory or relapsed multiple myeloma: a retrospective study based on LEGEND-2].

Objective: To explore the dynamic changes in serum lipid levels and nutritional status during BCMA-CAR-T-cell therapy in patients with refractory or relapsed multiple myeloma (R/R MM) based on LEGEND-2. Methods: The data of patients with R/R MM who underwent BCMA-CAR-T therapy at our hospital between March 30, 2016, and February 6, 2018, were retrospectively collected. Serum lipid levels, controlled nutritional status (CONUT) score, and other clinical indicators at different time points before and after CAR-T-cell infusion were compared and analyzed. The best cut-off value was determined by using the receiver operator characteristic (ROC) curve. The patients were divided into high-CONUT score (>6.5 points, malnutrition group) and low-CONUT score groups (≤6.5 points, good nutrition group), comparing the progression-free survival (PFS) and total survival (OS) of the two groups using Kaplan-Meier survival analysis. Results: Before the infusion of CAR-T-cells, excluding triglycerides (TG), patients' serum lipid levels were lower than normal on average. At 8-14 d after CAR-T-cell infusion, serum albumin (ALB), total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and apolipoprotein A1 (Apo A1) levels dropped to the minimum, whereas CONUT scores reached the maximum. In addition to TG, apolipoprotein B (Apo B) levels increased compared with baseline. After CAR-T-cell therapy, the patients' serum lipid levels significantly increased with well-improved nutritional status. Spearman's related analysis showed that TC, HDL, and ApoA1 levels after CAR-T-cell injection were significantly negatively correlated with the grade of cytokine-release syndrome (CRS) (r=-0.548, P=0.003; r=-0.444, P=0.020; r=-0.589, P=0.001). Furthermore, survival analysis indicated that the CONUT score was unrelated to PFS, and the median OS of patients with R/R MM in the high-CONUT score group was shorter than that in the low-CONUT score group (P=0.046) . Conclusions: During CAR-T-cell therapy, hypolipidemia and poor nutritional status were aggravated, which is possibly related to CRS. The patients' serum lipid levels and nutritional status were significantly improved after CAR-T-cell treatment. The CONUT score affected the median OS in patients treated with CAR-T-cells. Therefore, specific screening and intervention for nutritional status in patients receiving CAR-T-cell therapy are required.

MTMR2 promotes the progression of NK/T cell lymphoma by targeting JAK1.

OBJECTIVE: The aim of this study was to investigate the expression characteristics of MTMR2 in NK/T cell lymphoma (NKTCL), and to further study its relationship with clinical parameters and the prognosis of patients with NKTCL. In addition, the potential mechanisms of MTMR2 promoting the progression of NKTCL was further explored. MATERIALS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was performed to examine MTMR2 level in peripheral blood of 45 patients with NK/T-cell lymphoma and 45 healthy volunteers. The interplay between MTMR2 expression and clinical indicators, as well as the prognosis of patients with NK/T-cell lymphoma was analyzed. Meanwhile, MTMR2 expression in NKTCL cell lines was verified by qRT-PCR. Subsequently, MTMR2 knockdown and the overexpression models were constructed using lentivirus in NKTCL cell lines, including SNK-6 and KHYG-1. Transwell invasion and cell wound healing assays were applied to analyze the effect of MTMR2 on the biological function of NKTCL cells. Finally, an in-depth study of the relationship between MTMR2 and JAK1 was conducted to explore the underlying mechanism. RESULTS: QRT-PCR results showed that the expression level of MTMR2 in the serum of patients with NKTCL was remarkably higher than that of healthy volunteers, and the difference was statistically significant (p<0.05). Compared with patients with low expression of MTMR2, patients with high expression of MTMR2 exhibited significantly higher incidence of distant metastasis and lower overall survival rate (p<0.05). The metastasis ability of NKTCL SNK-6 cells was remarkably attenuated in MTMR2 knockdown group when compared with the negative control sh-NC group (p<0.05). Meanwhile, the metastatic ability of NKTCL KHYG-1 cells in MTMR2 overexpressing group was remarkably enhanced when compared with the control NC group (p<0.05). The Luciferase reporter gene assay confirmed that MTMR2 could target JAK1, thereby jointly regulating the malignant progression of NKTCL. In addition, cell recovery experiment verified that JAK1 could partially reverse the enhanced metastatic ability of NKTCL cells induced by the overexpression of MTMR2. CONCLUSIONS: MTMR2 was highly expressed in NKTCL serum samples and cell lines, leading to high risk of distant metastasis and poor prognosis. In addition, MTMR2 might promote the malignant progression of NKTCL by regulating JAK1.

Ginsenoside Rg1 protects chronic cyclosporin a nephropathy from tubular cell apoptosis by inhibiting endoplasmic reticulum stress in rats.

INTRODUCTION: This study tested the effect of ginsenoside Rg1 (G-Rg1) in cyclosporin A (CsA)-induced endoplasmic reticulum (ER) stress on renal tubular cell apoptosis in a rat model of chronic CsA nephropathy. MATERIALS AND METHODS: Twenty-two Sprague-Dawley rats were randomized into 3 groups: a control group, a model group (CsA 25 mg/kg per day), and a G-Rg1 treatment group (CsA 25 mg/kg per day and G-Rg1 20 mg/kg per day). We examined the effects of G-Rg1 on histopathology, terminal deoxynucleotidyl transferase dUTP nick-end labeling staining, and expression of glucose-regulated protein 78, CCAAT/enhancer-binding protein homologous protein, and caspase-3 by using Western blot analysis. RESULTS: G-Rg1 attenuated CsA-induced tubulointerstitial fibrosis and reduced tubular epithelial cell apoptosis as assessed by terminal deoxynucleotidyl transferase dUTP nick-end labeling staining and caspase-3 expression. Compared with the model group, it reduced the expression of glucose-regulated protein 78 and CCAAT/enhancer-binding protein homologous protein (0.12 ± 0.03 vs 0.48 ± 0.05 [P < .01]; 0.55 ± 0.11 vs 1.08 ± 0.07 [P < .05]), respectively. CONCLUSIONS: G-Rg1 mitigates the progression of chronic CsA nephropathy, at least in part, through inhibition of ER stress-triggered tubular cell apoptosis.

Adsorption of an Mn atom on a ZnO sheet and nanotube: a density functional theory study.

First-principles calculations based on density functional theory were performed to study the stable geometries, electronic structure and magnetic properties of the adsorption of a single Mn atom on a graphitic ZnO sheet and a (9, 0) single-wall ZnO nanotube. For the graphitic ZnO sheet, the Mn atom prefers to reside above the center of a hexagon (H site), with a relatively large binding energy of 1.24 eV. The H site is also the most stable site for adsorption of an Mn atom inside the ZnO nanotube, with a large binding energy of 1.47 eV. In both of these cases, the total magnetic moment is 5.0 µ(B) per Mn atom, which is the same as that of a free Mn atom. When the Mn atom is adsorbed outside the tube, the most energetically favorable site is the atop oxygen site. The magnetic moment is 3.19 µ(B) for this configuration. The smaller magnetic moment is mainly due to the strong p-d mixing of O and Mn orbitals. The different adsorption behaviors are related to the curvatures of the nanostructures.