Progress and prospect of ASCT combined with CAR-T therapy in the treatment of multiple myeloma.

Multiple myeloma (MM) is a hematological cancer characterized by abnormal proliferation of plasma cells in bone marrow. In recent years, autologous stem cell transplantation (ASCT) has become the cornerstone of MM treatment. At the same time, immunotherapy, such as monoclonal antibody therapy and chimeric antigen receptor T cell (CAR-T) has also emerged, in which CAR-T is the most attractive focus. ASCT and its myeloablative preconditioning will turn its immune microenvironment into an inhibited state, which may provide an opportunity for the expansion of CAR-T cells so as to further clear the residual lesions after ASCT and reduce the recurrence rate after ASCT. Meanwhile, the infusion of CAR-T cells can accelerate the cellular immune reconstruction after ASCT of myeloma, thereby improving the antitumor effect. In order to explore the clinic value, this article reviews the progress and prospect of ASCT combined with CAR-T therapy in the treatment of MM.

Seasonal change of microplastics uptake in the Pacific oysters Crassostrea gigas cultured in the Yellow Sea and Bohai Sea, China.

This study investigated seasonal microplastics (MPs) pollution characteristics in oysters and surrounding surface seawater from five aquaculture farms located at the Yellow Sea and Bohai Sea. MPs abundances in oysters were 2.40 ± 0.14 (winter) to 3.28 ± 0.19 (autumn) items/individual, and 0.22 ± 0.02 (spring) to 0.45 ± 0.06 (summer) items/g (ww). In surface seawater, average seasonal MPs abundances were 3.41 ± 1.06-8.86 ± 2.48 items/L. Fibers were dominant shape, and cellophane and polyethylene terephthalate (PET) were dominant polymers in oysters and surface seawater. Positive correlation was found between oysters' MPs abundance (items/individual) and environmental factors (NO2-N (r = 0.466), and temperature (r = 0.485)) by Spearman correlation analysis in four seasons. Main environmental factor affecting seasonal MPs abundance of oysters and surface seawater was NH3-N and SiO3-Si in summer and winter respectively. In conclusion, seasonal change of MPs uptake in cultured oysters was relatively small.

Hydrogen-rich water alleviates cyclosporine A-induced nephrotoxicity via the Keap1/Nrf2 signaling pathway.

Oxidative stress induced by long-term cyclosporine A (CsA) administration is a major cause of chronic nephrotoxicity, which is characterized by tubular atrophy, tubular cell apoptosis, and interstitial fibrosis in the progression of organ transplantation. Although hydrogen-rich water (HRW) has been used to prevent various oxidative stress-related diseases, its underlying mechanisms remain unclear. This study investigated the effects of HRW on CsA-induced nephrotoxicity and its potential mechanisms. After administration of CsA (25 mg/kg/day), rats were treated with or without HRW (12 mL/kg) for 4 weeks. Renal function and vascular activity were investigated. Histological changes in kidney tissues were analyzed using Masson's trichrome and terminal deoxynucleotidyl transferase dUTP nick-end labeling stains. Oxidative stress markers and the activation of the Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway were also measured. We found that CsA increased the levels of reactive oxygen species (ROS) and malonaldehyde (MDA), but it reduced glutathione (GSH) and superoxide dismutase (SOD) levels. Such alterations induced vascular dysfunction, tubular atrophy, interstitial fibrosis, and tubular apoptosis. This was evident secondary to an increase in urinary protein, serum creatinine, and blood urea nitrogen, ultimately leading to renal dysfunction. Conversely, HRW decreased levels of ROS and MDA while increasing the activity of GSH and SOD. This was accompanied by an improvement in vascular and renal function. Moreover, HRW significantly decreased the level of Keap1 and increased the expression of Nrf2, NADPH dehydrogenase quinone 1, and heme oxygenase 1. In conclusion, HRW restored the balance of redox status, suppressed oxidative stress damage, and improved kidney function induced by CsA via activation of the Keap1/Nrf2 signaling pathway.