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Although telitacicept is a promising drug for treating systemic lupus erythematosus, there are limited studies on its efficacy and safety in patients with lupus nephritis in China. This lack of research data restricts its potential for broader application and acceptance on a global scale. The present study aimed to determine the efficacy and safety of telitacicept in patients with lupus nephritis (LN) in China. Using a self-controlled before-after comparison method, patients with LN were recruited at Lishui Central Hospital between February 2022 and April 2023, who received telitacicept weekly as part of the standard treatment. Data on the systemic lupus erythematosus disease activity index 2000 (SLEDAI-2K), glucocorticoid dosing and the quantity of immunosuppressive medicines prescribed was collected. Additionally, serum complements, erythrocyte sedimentation rate (ESR), urinary protein levels, immunoglobulin concentrations, serum creatinine levels, plasma albumin concentrations, platelet counts and renal function parameters were documented throughout the study. A total of 13 patients were enrolled in the trial, comprising 11 women and two men. Following 12-48 weeks of treatment with telitacicept (80 or 160 mg per week), 84.6% (n=11) of all patients experienced symptom relief and their SLEDAI-2K score was reduced by more than four points. By the observation endpoint, the median glucocorticoid dosage of the 13 patients was decreased from 15 to 2.5 mg/d, and six patients discontinued their glucocorticoids. Furthermore, 46.1% of patients (n=6) reduced their dose and number of immunosuppressive medicines, while 15.4% (n=2) stopped their immunosuppressive medicines. Minimal changes were observed in serum creatinine, platelet count, C3 levels and C4 levels among patients. Immunoglobulin levels (IgG, IgA and IgM) remained stable or showed an upward trend. Plasma albumin levels remained within the normal range in three patients and increased in ten patients. It increased to the normal range in three of these ten patients. At the endpoint, ESR levels decreased in all patients. Additionally, three patients displayed varying degrees of renal function improvement, and their estimated glomerular filtration rate (ml/min/l.73 m2) increased from 127.8 to 134.2, 95.1 to 123.1 and 61.5 to 67.3, respectively. Urinary protein levels decreased in all patients. It decreased >0.5 g/l in seven patients and reached the normal levels in three patients. The adverse events of telitacicept were manageable. Among the patients infected with COVID-19, three patients had fever, 10 patients remained asymptomatic and none of them exhibited severe respiratory syndromes. In this study, telitacicept effectively stabilized LN activity and alleviated the clinical symptoms of most patients. Furthermore, it reduced the dose of glucocorticoid and immunosuppressive medicines. Therefore, telitacicept may be a promising treatment option for individuals with lupus nephritis. [ABSTRACT FROM AUTHOR]

Age-associated diseases, including vascular diseases, are on the rise with the increase in the aging population. However, the mechanisms of aging and age-associated vascular dysfunction remain to be fully elucidated. Replicative senescence of vascular smooth muscle cells (VSMCs) contributes to aging as well as age-associated vascular diseases. Rapamycin may delay aging-associated diseases via inhibition of the mammalian target of rapamycin (mTOR), but its role in VSMC aging has remained elusive. The present study investigated the involvement of mTOR signaling in replicative senescence of VSMCs. Replicative senescence was induced in human VSMCs by extended passages and identified by assessing the cell morphology, senescence-associated β-galactosidase activity, and p53 and p21 protein expression. Protein expression and phosphorylation were determined by western blot analysis. Significant senescence of VSMCs was observed in cells subjected to extended passaging (until passage 15). Significant decreases in adenosine monophosphate-activated protein kinase (AMPK)/tuberous sclerosis complex 2 (TSC2) phosphorylation, but significant increases in mTOR/ribosomal protein S6 kinase 1 (S6K1) phosphorylation, were observed in cells with replicative senescence compared with those in young cells. Pre-treatment of VSMCs with AMPK activator and mTOR inhibitor delayed replicative senescence and reversed changes in AMPKα, TSC2, mTOR and S6K1 phosphorylation in senescent VSMCs. The AMPK/TSC2/mTOR/S6K1 signaling axis was found to have an important role in regulating replicative senescence of human VSMCs. [ABSTRACT FROM AUTHOR]

The fragile histidine triad (FHIT) gene is known to be a tumor suppressor gene and the abnormal methylation of FHIT has been identified in leukemia and several solid tumors. The transformation of the tumor F6 cell line from human fetal mesenchymal stem cells (FMSCs) was first reported in a previous study that also identified the presence of a population of cancer stem cells in the F6 cell line. However, the existence of the epigenetic changes during the transformation process have yet to be elucidated. To confirm the role of the FHIT gene in the transformation process of FMSC, the expression level and methylation status of the FHIT gene was examined in F6 tumor cells and FMSCs. Additionally, the alteration in cell morphology, the cell cycle and apoptosis in F6 cells following 5-Aza-CdR treatment was assessed. It was found that the FHIT gene was expressed in FMSCs, but not in F6 cells. The methylation-specific PCR results demonstrated that the promoter methylation of FHIT genes existed in the F6 cell line. Subsequent to treatment with 5-Aza-CdR the expression of FHIT genes was restored in F6 cells. In addition, the morphology of F6 cells was altered, and the cell cycle was arrested in the G2 phase, with the initiation of apoptosis. Overall, the present findings demonstrated that the FHIT gene was methylated in F6 cells and demethylation treatment lead to changes in the biological characteristics, thereby promoting the apoptosis of F6 cells. FHIT gene methylation may be one of the molecular events involved in the development and transformation of FMSCs into F6 tumor cells. [ABSTRACT FROM AUTHOR]

Human bone marrow mesenchymal stem cells (hBM-MSCs) favor tumor growth and metastasis in vivo and in vitro. Neovascularization is involved in several pathological conditions, including tumor growth and metastasis. Previous studies have demonstrated that human bone marrow MSC-derived conditioned medium (hBM-MSC-CM) can promote tumor growth by inducing the expression of vascular epidermal growth factor (VEGF) in tumor cells. However, the effect of BM-MSCs on tumor lymph vessel formation has yet to be elucidated. In the present study, the effect of BM-MSCs on processes involved in lymph vessel formation, including tube formation, migration and proliferation, was investigated in human-derived lymphatic endothelial cells (HDLECs). It was identified that hBM-MSC-CM promoted the tube formation and migration of HDLECs. In addition, tumor cells were revealed to participate in lymph vessel formation. In the present study, the SGC-7901, HGC-27 and GFP-MCF-7 cell lines were treated with hBM-MSC-CM. The results demonstrated that the expression of the lymph-associated markers, prospero homeobox protein 1 and VEGF receptor-3, were increased in the SGC-7901 and HGC-27 cell lines, but not in the GFP-MCF-7 cells. The tube formation assay demonstrated that the HGC-27 cells treated with hBM-MSC-CM for 20 days underwent tube formation. These findings indicate that hBM-MSC-CM can promote tube formation in HDLECs and HGC-27 cells, which may be associated with lymph vessel formation during tumor growth and metastasis. [ABSTRACT FROM AUTHOR]

An immortalized mouse fetal liver stromal cell line, named KM3, has demonstrated the potential to support the growth and maintenance of human embryonic stem cells (hESCs). In this study, the characteristics of KM3 cells were examined following cryopreservation at -70°C and in liquid nitrogen for 15, 30 and 60 days following treatment with 10 µg/ml mitomycin C. In addition, whether the KM3 cells were suitable for use as feeder cells to support the growth of hESCs was evaluated. The inhibition of mitosis without cell death was observed when the KM3 cells were treated with 10 µg/ml mitomycin C for 2 h. The morphology of the KM3 cells cryopreserved in liquid nitrogen for 60 days was not markedly changed, and the cell survival rate was 84.60±1.14%. By contrast, the survival rate of the KM3 cells was 66.40±2.88% following cryopreservation at -70°C for 60 days; the cells readily detached, were maintained for a shorter time, and had a reduced expression level of basic fibroblast growth factor. hESCs cultured on KM3 cells cryopreserved in liquid nitrogen for 60 days showed the typical bird's nest structure, with clear boundaries and a differentiation rate of 16.33±2.08%. The differentiation rate of hESCs cultured on KM3 cells cryopreserved at -70°C for 60 days was 37.67±3.51%. These results indicate that the cryopreserved KM3 cells treated with mitomycin C may be directly used in the subculture of hESCs, and the effect is relatively good with -70°C short-term or liquid nitrogen cryopreservation. [ABSTRACT FROM AUTHOR]