Adiponectin Receptor Agonist Effectively Suppresses Hepatocellular Carcinoma Growth.

Hepatocellular carcinoma (HCC) is the second lethal cancer. Short overall survival, low five-year survival rate, and unimproved treatment efficacy urge the need to improve HCC prognosis. Adiponectin is key protector against cancer and hepatic abnormalities. Hypoadiponectinemia occurs in and promotes carcinogenesis and hepatic diseases. Adiponectin reactivation by different methods showed impressive effect against cancer and hepatic diseases. Recently, AdipoRon, an adiponectin receptor agonist, can interact with both Adiponectin receptors. AdipoRon showed promising anti-cancer effect in some cancers, but no study on HCC yet. The in vitro effect of AdipoRon on HCC was investigated by cell viability, migration, invasion, colony formation and apoptosis assays. The signalling alteration was determined by RT-qPCR and Western blot. The effect of treatment was interpreted by comparison between treatments and control. The difference between two cell lines was relatively compared. Our results showed significant in vitro anti-cancer effect of AdipoRon via AMPK- and dose-dependent manner. Huh7 cells showed a lower level of AdipoR1/2 and a superior proliferation and aggressiveness, compared to Hep3B. In addition, Huh7 cells were more sensitive to AdipoRon treatment (lower IC50, less cell growth, migration, invasion and colonies upon AdipoRon treatment) than Hep3B cells. In conclusion, AdipoRon effectively inhibited HCC growth and invasiveness in vitro. The deficient expression of adiponectin receptors affects efficacy of AdipoRon and aggressiveness of HCC cells.

Higher tacrolimus trough levels and time in the therapeutic range are associated with the risk of acute rejection in the first month after renal transplantation.

BACKGROUND: Tacrolimus trough levels (C0) are used in most transplant centres for therapeutic drug monitoring (TDM) of tacrolimus (Tac). The target range of Tac C0 has been remarkably changed, with a target as low as 3-7 ng/ml in the 2009 European consensus conference and a target of 4-12 ng/ml (preferably to 7-12 ng/ml) following the second consensus report in 2019. Our aim was to investigate whether reaching early Tac therapeutic targets and maintaining time in the therapeutic range (TTR) according to the new recommendations may be necessary for preventing acute rejection (AR) during the first month after transplantation. METHODS: A retrospective study including 160 adult renal transplant patients (113 men and 47 women) with a median age of 36.3 (20-44) years was conducted between January 2018 and December 2019 at 103 Military Hospital (Vietnam). Tac trough levels were recorded in the first month, and episodes of AR were confirmed by kidney biopsy. Tac TTR was calculated as the percentage of time within the target range of 7-12 ng/ml, according to the 2019 second consensus report. Multivariate Cox analysis was performed to identify the correlation between the Tac target range and TTR with AR. RESULTS: In the first month after RT, 14 (8.8%) patients experienced AR. There was a significant difference in the incidence of AR between the Tac level groups of < 4, 4-7 and > 7 ng/ml (p = 0.0096). In the multivariate Cox analysis, after adjusting for related factors, a mean Tac level > 7 ng/ml was associated with an 86% decreased risk of AR compared with that of 4-7 ng/ml in the first month (HR, 0.14; 95% CI, 0.03-0.66; p = 0.0131). Every 10% increase in TTR was associated with a 28% lower risk of AR (HR, 0.72; 95% CI, 0.55-0.94; p = 0.014). CONCLUSION: Gaining and maintaining Tac C0 according to the 2019 second consensus report might reduce the risk of AR in the first month following transplantation.

Allogeneic umbilical cord-derived mesenchymal stem cell transplantation for treating chronic obstructive pulmonary disease: a pilot clinical study.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide. COPD results from chronic inflammation of the lungs. Current treatments, including physical and chemical therapies, provide limited results. Stem cells, particularly mesenchymal stem cells (MSCs), are used to treat COPD. Here, we evaluated the safety and efficacy of umbilical cord-derived (UC)-MSCs for treating COPD. METHODS: Twenty patients were enrolled, 9 at stage C and 11 at stage D per the Global Initiative for Obstructive Lung Disease (GOLD) classification. Patients were infused with 106 cells/kg of expanded allogeneic UC-MSCs. All patients were followed for 6 months after the first infusion. The treatment end-point included a comprehensive safety evaluation, pulmonary function testing (PFT), and quality-of-life indicators including questionnaires, the 6-min walk test (6MWT), and systemic inflammation assessments. All patients completed the full infusion and 6-month follow-up. RESULTS: No infusion-related toxicities, deaths, or severe adverse events occurred that were deemed related to UC-MSC administration. The UC-MSC-transplanted patients showed a significantly reduced Modified Medical Research Council score, COPD assessment test, and number of exacerbations. However, the forced expiratory volume in 1 s, C-reactive protein, and 6MWT values were nonsignificantly reduced after treatment (1, 3, and 6 months) compared with those before the treatment. CONCLUSION: Systemic UC-MSC administration appears to be safe in patients with moderate-to-severe COPD, can significantly improve their quality of life, and provides a basis for subsequent cell therapy investigations. TRIAL REGISTRATION: ISRCTN, ISRCTN70443938. Registered 06 July 2019.