Chromobox (CBX) proteins are important components of epigenetic regulation complexes known to play key roles in hepatocellular carcinoma (HCC). Little is known about the function of distinct CBXs in HCC. To address this issue, the study investigated the roles of CBXs in the prognosis of HCC using ONCOMINE, UALCAN, Human Protein Atlas, Kaplan-Meier Plotter, c-BioPortal databases. Over expressions of 8 CBXs members were found to be significantly associated with clinical cancer stages and pathological tumor grades in HCC patients. Besides, higher mRNA expressions of CBX1/2/3/6/8 were found to be significantly associated with shorter overall survival (OS) in HCC patients, while higher mRNA expression of CBX7 was associated with favorable OS. Multivariate analysis also showed that high mRNA expressions of CBX1/2/3/6/8 were independent prognostic factors for shorter OS of HCC patients. Moreover, high mutation rate of CBXs (51%) was also observed in HCC patients, and genetic alteration in CBXs was associated with shorter OS and disease-free survival (DFS) in HCC patients. Taken together, these results indicated that CBX1/2/3/6/8 could be prognostic biomarkers for survivals of HCC patients.

Mesenchymal stromal cells (MSCs) can differentiate to various cell types including osteoblasts, chondrocytes, and adipocytes. This cellular flexibility contributes to widespread clinical use of MSCs in tissue repair. However, challenges remain in efficient cellular expansion of MSCs for stem cell therapy. Current MSC culture methods have resulted in reduced self-renewal of MSCs and compromised therapeutic outcomes. This study identifies that nicotinamide mononucleotide (NMN), a key natural NAD + intermediate, effectively encourages MSC expansion in vitro and in vivo. The in vitro expanded MSCs had heightened osteogenesis, but reduced adipogenesis. Furthermore, NMN supplementation stimulated osteogenesis of endogenous MSCs, and protected bone from aging and irradiation induced damage in mice. Mechanistically, we found that NMN treatment upregulated SIRT1. Genetically overexpressing SIRT1 in MSCs by using Prx1 cre; ColA1 flox-stop-flox-SIRT1 mice promoted osteogenesis and reduced adipogenesis in aged mice. Overall, our data demonstrate that NMN promoted MSC self-renewal with strengthened osteogenesis and reduced adipogenesis via upregulating SIRT1 in aged mice.

Hepatitis B virus (HBV) reactivation during or after chemotherapy in patients with breast cancer has become a remarkable clinical problem. Prophylactic nucleos(t)ide analogues (NAs) are recommended for patients with breast cancer who are hepatitis B surface antigen (HBsAg) positive before chemotherapy. We performed an up-to-date meta-analysis to compare the efficacy of prophylactic lamivudine use with nonprophylaxis in HBsAg-positive breast cancer patients undergoing chemotherapy. PubMed, the Cochrane Library and China National Knowledge Infrastructure (CNKI) databases were searched for relevant articles until June 2016. Eligible articles comparing the efficacy of prophylactic lamivudine use with nonprophylaxis in HBsAg-positive breast cancer patients undergoing chemotherapy were identified. Eight studies which had enrolled 709 HBsAg-positive breast cancer patients undergoing chemotherapy were analysed. Lamivudine prophylaxis significantly reduced the rates of chemotherapy-associated hepatitis B flares in chronic hepatitis B in breast cancer compared with patients with nonprophylaxis (odds ratio [OR]=0.15, 95% confidence interval [CI]: 0.07-0.35, P<.00001). Chemotherapy disruption rates attributed to HBV reactivation in the prophylaxis groups were significantly lower than the nonprophylaxis groups (OR=0.17, 95% CI: 0.07-0.43, P=.0002). Patients with lamivudine prophylaxis had a higher risk for tyrosine-methionine-aspartate-aspartate (YMDD) motif mutations than patients with nonprophylaxis (OR=6.33, 95% CI: 1.01-39.60, P=.05). Prophylactic antiviral therapy management is necessary for HBsAg-positive breast cancer patients undergoing chemotherapy, in spite of high correlation with lamivudine-resistant HBV variants with YMDD motif mutations.

The sodium taurocholate co-transporting polypeptide (NTCP) acts as a cellular receptor for the hepatitis B virus (HBV) infection on host hepatocytes. We aim to investigate how the NTCP p.Ser267Phe variant affects HBV-related disease progression and analyze viral genomic variability under a host genetic background carrying the p.Ser267Phe variant. A total of 3187 chronic hepatitis B (CHB) patients were enrolled and genotyped for the p.Ser267Phe variant. The variant's association with disease progression was evaluated by logistic regression analysis. We also enrolled 83 treatment-naive CHB patients to analyze the variability of the HBV preS1 region. The frequency of the NTCP p.Ser267Phe variant was significantly lower in patients diagnosed with acute-on-chronic liver failure [OR (95% CI) = 0.33 (0.18–0.58), P = 1.34 × 10 −4 ], cirrhosis [OR (95% CI) = 0.47 (0.31–0.72), P = 4.04 × 10 −4 ], and hepatocellular carcinoma [OR (95% CI) = 0.54 (0.34–0.86), P = 9.83 × 10 −3 ] as compared with CHB controls under the additive model after adjustment. Furthermore, the percentage of amino acid mutations in HBV preS1 region was significantly higher in the NTCP p.Ser267Phe heterozygote group than in the NTCP wild type homozygote group ( P < 0.05). We herein demonstrate that the NTCP p.Ser267Phe variant is a protective factor reducing CHB patient risk for liver failure, cirrhosis, and hepatocellular carcinoma. A host genetic background carrying NTCP p.Ser267Phe exerts selective pressure on the virus, leading to more variability.

Background and Aims:The safety and efficacy of mesenchymal stem cells (MSCs) in the treatment of acute-onchronic liver failure (ACLF) have been validated. However, the impact of the pathological ACLF microenvironment on MSCs is less well understood. This study was designed to explore the changes in the functional properties of MSCs exposed to ACLF serum. Methods: MSCs were cultured in the presence of 10%, 30% and 50% serum concentrations from ACLF patients and healthy volunteers. Then, the cell morphology, phenotype, apoptosis and proliferation of MSCs were evaluated, including the immunosuppressive effects. Subsequently, mRNA sequencing analysis was used to identify the molecules and pathways involved in MSC functional changes in the context of ACLF. Results: In the presence of ACLF serum, MSC morphology significantly changed but phenotype did not. Besides, MSC proliferation activity was weakened, while the apoptosis rate was lightly increased. Most importantly, the immunosuppressive function of MSCs was enhanced in a lowconcentration serum environment but transformed into a proinflammatory response in a high-concentration serum environment. RNA sequencing indicated that 10% serum concentration from ACLF patients mediated the PI3K-Akt pathway to enhance the anti-inflammatory effect of MSCs, while the 50% serum concentration from ACLF patients promoted the conversion of MSCs into a proinflammatory function by affecting the cell cycle. Conclusions: The 50% ACLF serum concentration is more similar to the en-vironment in the human body, which means that direct peripheral blood intravenous infusion of MSCs may reduce the effect of transplantation. Combining treatments of plasma exchange to reduce harmful substances in serum may promote MSCs to exert a stronger anti-inflammatory effect.