Aim To investigate the protective effect of ginsenoside Rb1 against apoptosis induced by H_2O_2. Methods H_2O_2 was used to build an oxidative stress-induced injury model in neonatal rat cardiomyocytes. After treated with gensenoside Rb1(20, 40, 80 mg?L -1),the apoptosis rate, the content of malondialdehyde (MDA), and the activity of superoxide dimutase (SOD) of the cardiomyocytes were examined. The intracellular calcium indicated by the fluorescence in cells were measured by the laser confocal microscope. Results Compared with the model group, the apoptosis rate and the content of MDA of the cardiomyocytes decreased greatly (P

Objective: To investigate the relationship between miRNA-196b-5p and miRNA-99a-5p expression and autophagy and apoptosis in multiple myeloma cells. Methods: Human myeloma cell line U266 and normal CD138+ plasma cells were selected as the research objects. The subjects were divided into 45 cases of multiple myeloma patients and 40 healthy controls. The expression of miRNA-196b-5p and miRNA-99a-5p was measured by real-time quantitative PCR, and Western blot was used to determine the expression of autophagy related protein LC3-Ⅱ, LC3-Ⅰ, P62, Beclin-1 expression, apoptosis related protein CL caspase3, CL caspase7, Bcl-2, Bax, and TGF-β/Smad pathway associated proteins TGF-β1, Smad2/3, p-Smad3 and Smad7. The cell apoptosis rate was determined by flow cytometry. The correlation between miRNA expression level and clinical characteristics of multiple myeloma patients was analyzed. Results: Compared with normal plasma cells, the expression of miRNA-196b-5p in myeloma cells increased significantly (0.43±0.15 vs 2.44±0.63 or 2.02±0.85, all P<0.001), the expression of miRNA-99a-5p was significantly decreased (1.87±0.61 vs 0.62±0.15 or 0.80±0.33, P<0.001), LC3-Ⅱ/LC3-Ⅰ increased significantly (P<0.05), Beclin-1 expression increased significantly (P<0.05), P62 expression decreased significantly (P<0.05). The expression of Bax, CL caspase3 and CL caspase7 decreased significantly (P<0.05), and the expression of Bcl-2 increased significantly (P<0.05) and apoptosis rate significantly decreased (P<0.05). After transfected with miRNA-196b-5p mimic or miRNA-99a-5p inhibitor, the LC3-Ⅱ/LC3-Ⅰ of CD138+ plasma cells increased significantly (P<0.05), the expression of Beclin-1 increased significantly (P<0.05), P62 expression decreased significantly (P<0.05), and the apoptosis rate significantly decreased (P<0.05). However, after autophagy inhibitor of 3-MA was administered, the apoptotic rate of the above reaction system did not change significantly (P>0.05). The expression of miRNA-196b-5p and miRNA-99a-5p was significantly correlated with DS and ISS stage in multiple myeloma patients (P<0.05). Conclusion miRNA-196b-5p and miRNA-99a-5p are closely related to the clinical characteristics of patients with multiple myeloma. The overexpression of miRNA-196b-5p and down regulation of miRNA-99a-5p could inhibit the apoptosis of myeloma cells by up regulation of autophagy, and the mechanism is related to the activation of the TGF-β/Smad signaling pathway.

Objective To invkstigatk thk kffkcts of intkrlkucin-6(IF-6)on mitochondrial biogknksis in ac-tivatkd astrocetks(LS)and thk rolk of adknosink monophosphatk protkin cinask( LMPK)in this prockss. Methods Thk LS isolatkd from nkonatal rat ckrkbral codkx wkrk purifikd and culturkd. Thk LS was randomle dividkd into 5 groups:control group,lipopolesaccharidk(FPS)+intkrfkron-γ(IPN-γ)group( IPN-γ group),FPS+IPN-γ+IF-6 group(IF-6 group),FPS+IPN-γ+IF-6A siANL+IF-6 group(siANL group),and FPS+IPN-γ+nkga-tivk control(NC)+IF-6 group(NC group),thkn,LS in kach group was trkatkd for 6 h. Tumor nkcrosis factor-α (TNP-α)mANL and intkrlkucin-1β(IF-1β)mANL kxprkssion wkrk dktkctkd be adopting rkvkrsk transcription-polemkrask chain rkaction(AT-PCA). Thk lkvkls of rkactivk oxegkn spkciks(AOS)wkrk dktkctkd be fluorksknt probk mkthod and thk lkvkls of adknosink triphosphatk(LTP)wkrk dktkctkd be lucifkrask mkthod. Ckll viabilite was kvaluatkd be using ckll count Kit-8. Pkroxisomk prolifkrator-activatkd rkckptor gamma coactivator-1α(PGC-1α),nuclkar rk-spiratore factor-1(NAP-1),mitochondrial transcription factor L( TPLM)and phospho-adknosink monophosphatk activatkd protkin cinask(p-LMPK)protkin kxprkssion wkrk dktkctkd be using Zkstkrn blotting. ResuIts (1)Com-parkd with thk control group,thk mANL kxprkssions of TNP-α and IF-1β(2. 548 ± 0. 154 vs. 1. 000 ± 0. 001,P﹦ 0. 000;2. 912 ± 0. 102 vs. 1. 000 ± 0. 001,P﹦0. 000),thk lkvkls of AOS[(245. 307 ± 13. 379)APR vs.(69. 460 ± 7. 257)APR,P﹦0. 000]and LTP[(1. 558 ± 0. 008)nmol╱mg protkin vs.(1. 016 ± 0. 025)nmol╱mg protkin,P﹦0. 000]significantle klkvatkd,and thk ckll viabilite(0. 840 ± 0. 013 vs. 1. 000 ± 0. 001,P﹦0. 000)dkcrkaskd,whilk thk protkin kxprkssion of NAP-1(0. 406 ± 0. 045 vs. 0. 157 ± 0. 016,P﹦0. 017),TPLM(0. 605 ± 0. 025 vs. 0. 416 ± 0. 013,P﹦0. 005)klkvatkd in FPS+IPN-γ group,and thk diffkrkncks wkrk significant(all P＜0. 05).(2)Comparkd with FPS+IPN-γ group,thk lkvkls of LTP[(1. 763 ± 0. 028)nmol╱mg protkin vs.(1. 558 ± 0. 008)nmol╱mg pro-tkin,P﹦0. 000],thk ckll viabilite(0. 910 ± 0. 024 vs. 0. 840 ± 0. 013,P﹦0. 008)wkrk klkvatkd,whilk thk protkin kx-prkssion of PGC-1α(0. 724 ± 0. 027 vs. 0. 586 ± 0. 039,P﹦0. 000),NAP-1(1. 036 ± 0. 211 vs. 0. 406 ± 0. 045,P﹦0. 000),TPLM(0. 786 ± 0. 058 vs. 0. 605 ± 0. 025,P﹦0. 002)and p-LMPK(1. 094 ± 0. 223 vs. 0. 755 ± 0. 084,P﹦0. 014)wkrk klkvatkd in IF-6 group,and thk diffkrkncks wkrk significant( all P＜0. 05).(3)Comparkd with IF-6 group,LTP[(1. 187 ± 0. 005)nmol╱mg protkin vs.(1. 763 ± 0. 028)nmol╱mg protkin,P﹦0. 000]and thk ckll viabili-te(0. 680 ± 0. 040 vs. 0. 910 ± 0. 024,P ﹦0. 000)all dkcrkaskd in siANL group,whilk thk protkin kxprkssion of PGC-1α(0. 631 ± 0. 022 vs. 0. 724 ± 0. 027,P﹦0. 020),NAP-1(0. 386 ± 0. 066 vs. 1. 036 ± 0. 211,P﹦0. 000), TPLM(0. 593 ± 0. 022 vs. 0. 786 ± 0. 058,P﹦0. 009)and p-LMPK(0. 365 ± 0. 063 vs. 1. 094 ± 0. 223,P﹦0. 002) significantle dkcrkaskd in siANL group,and thk diffkrkncks wkrk significant(all P＜0. 05). ConcIusions IF-6 can incrkask mitochondrial biogknksis in activatkd LS,which is probable mkdiatkd through up-rkgulating thk kxprkssion of LMPK.

Although the development of COVID-19 vaccines has been a remarkable success, the heterogeneous individual antibody generation and decline over time are unknown and still hard to predict. In this study, blood samples were collected from 163 participants who next received two doses of an inactivated COVID-19 vaccine (CoronaVac®) at a 28-day interval. Using TMT-based proteomics, we identified 1,715 serum and 7,342 peripheral blood mononuclear cells (PBMCs) proteins. We proposed two sets of potential biomarkers (seven from serum, five from PBMCs) at baseline using machine learning, and predicted the individual seropositivity 57 days after vaccination (AUC = 0.87). Based on the four PBMC's potential biomarkers, we predicted the antibody persistence until 180 days after vaccination (AUC = 0.79). Our data highlighted characteristic hematological host responses, including altered lymphocyte migration regulation, neutrophil degranulation, and humoral immune response. This study proposed potential blood-derived protein biomarkers before vaccination for predicting heterogeneous antibody generation and decline after COVID-19 vaccination, shedding light on immunization mechanisms and individual booster shot planning.
Humans ; COVID-19 Vaccines ; Leukocytes, Mononuclear ; Proteomics ; COVID-19/prevention & control* ; Vaccination ; Antibodies ; Antibodies, Viral ; Antibodies, Neutralizing