Increasing evidence indicates that brown adipose tissue (BAT) transplantation enhances whole-body energy metabolism in a mouse model of diet-induced obesity. However, it remains unclear whether BAT also has such beneficial effects on genetically obese mice. To address this issue, we transplanted BAT from C57/BL6 mice into the dorsal subcutaneous region of age- and sex-matched leptin deficient Ob/Ob mice. Interestingly, BAT transplantation led to a significant reduction of body weight gain with increased oxygen consumption and decreased total body fat mass, resulting in improvement of insulin resistance and liver steatosis. In addition, BAT transplantation increased the level of circulating adiponectin, whereas it reduced the levels of circulating free T3 and T4, which regulate thyroid hormone sensitivity in peripheral tissues. BAT transplantation also increased β3-adrenergic receptor and fatty acid oxidation related gene expression in subcutaneous and epididymal (EP) white adipose tissue. Accordingly, BAT transplantation increased whole-body thermogenesis. Taken together our results demonstrate that BAT transplantation may reduce obesity and its related diseases by activating endogenous BAT.

To investigated the effect of S6K1 on the replication and transcription of HBV DNA using multiple cell models.

Injectable hydrogels with high anti-inflammatory and wound-healing properties are highly desirable for clinical application. In the present study, injectable hydrogels were prepared based on carboxymethyl chitosan and oxidized hyaluronic acid. Blueberry anthocyanins (BA), which are known for their antioxidant and antiinflammatory properties, were successfully loaded into the hydrogels. The gelation kinetics and mechanical properties of the hydrogels were investigated. Oxidized hyaluronic acid with an oxidation degree of 38.1% conferred a suitable gelation time (~70 s) and mechanical properties (76.0 kPa compression stress at strain of 80%) of the hydrogel. The injectable BA-loaded hydrogel significantly accelerated the wound healing process in a full-thickness skin wound model in rats, promoted epithelial and tissue regeneration, exerted antiinflammatory effects, and promoted collagen deposition and angiogenesis. Besides, the hydrogel could upregulate the expression of VEGF and IL-10 proteins, downregulate the NF-κB level, and promote macrophage transformation from M1 phenotype to M2. The promotion of the BA-loaded hydrogel on wound healing were mainly realized by its biological effects, including antioxidant and anti-inflammatory effects, and regulation of various wound healing related factors. The results suggested that BA and the hydrogels exert synergistic effects in promoting wound healing. Injectable BA-loaded hydrogels appear to be promising candidates for wound healing application.

Recent studies have shown the effect of microRNAs on HSC activation and transformation, which is essential for the pathogenesis of liver fibrosis. In our study, we explored the role of miR-185 in liver fibrosis. Plasma miR-185 was detected in hepatitis B virus-related liver fibrosis patients (S2/3, n = 10) by Illumina HiSeq sequencing, and healthy volunteers were selected (n = 8) as the control group. We found that the plasma miR-185 level in fibrosis patients was significantly downregulated. CCl4-induced fibrosis tissues in mouse livers and TGF-β1-activated HSCs also presented downregulated miR-185 concomitant with an increased expression of RHEB and RICTOR. To explore the correlations, LX-2 cells were transiently transfected with miR-185 mimics. The expression levels of α-SMA, collagen I, and collagen III were decreased as well as RHEB and RICTOR. Inhibition of endogenous miR-185 increased fibrogenic activity. Furthermore, dual-luciferase reporter assays indicated that miR-185 inhibited the expression of RHEB and RICTOR by directly targeting their 3' UTRs. Moreover, silencing RHEB and RICTOR suppressed α-SMA and collagen expression levels. In conclusion, miR-185 prevents liver fibrogenesis by inhibiting HSC activation via inhibition of RHEB and RICTOR. These results provide new insights into the mechanisms behind the anti-fibrotic effect of miR-185.

PreS1-binding protein (PreS1BP), recognized as a nucleolar protein and tumor suppressor, influences the replication of various viruses, including vesicular stomatitis virus (VSV) and herpes simplex virus type 1 (HSV-1). Its role in hepatitis B virus (HBV) replication and the underlying mechanisms, however, remain elusive.

Hepatocellular carcinoma (HCC) is one of the most common cancer in the world and the main cause of cancer death. Chronic hepatitis B virus (HBV) infection is the major cause of HCC. HBx, as a transactivator, plays an important role in the occurrence and development process of HCC leading by HBV infection. XTP8, related to HBx, however, there are no studies on the function of XTP8 in HCC. In our research, we demonstrated that XTP8 was significantly up-regulated in HCC tissues compared with non-cancerous tissues in Oncomine, TCGA and GEO database. Moreover, Kaplan-Meier Plotter analysis indicated that patients with higher XTP8 expression had significantly lower overall survival. Our immunohistochemical results suggested that XTP8 protein expression in HCC tissues was dramatically higher compared with control normal tissues. In vivo xenograft experiments on nude mice, the overexpression of XTP8 promoted the tumorigenic ability of HepG2 cells. In HepG2 and Huh7 cells, XTP8 upregulated FOXM1 expression to promote cell proliferation and inhibited cell apoptosis. FOXM1 knockdown reduced promoter activity of XTP8 to downregulate XTP8 expression. Thiostrepton, an inhibitor of FOXM1, decreased XTP8 expression. Therefore, our study demonstrates that XTP8 is a valuable prognostic predictor for HCC and there is a novel positive regulatory feedback loop between XTP8 and FOXM1 promoting the development of HCC.

The effect of hepatitis C virus p7 trans-regulated protein 3 (P7TP3) in the development of hepatocellular carcinoma (HCC) is still unknown. The present study aimed to investigate the role and mechanism of P7TP3 in HCC. P7TP3 was significantly decreased in HCC tissues when compared with corresponding liver tissues immediately around the tumor (LAT) from seven HCC patients. Fewer and smaller colonies originated from HepG2-P7TP3 cells when compared to HepG2-NC cells. Overexpression of P7TP3 in HepG2 cells significantly repressed the growth of HCC xenografts in nude mice. Furthermore, wound-healing tests, Transwell assays, Matrigel Transwell assays, adhesion assays, CCK-8 assays, flow cytometry and western blotting analysis showed that P7TP3 protein expression inhibited migration, invasion, adhesion, proliferation and cell cycle progression in HCC cell lines. Moreover, P7TP3 suppressed the activity of the Wnt/β-catenin signaling pathway, and was restored by Wnt3a, which is an activator of the Wnt/β-catenin signaling pathway. Consistently, β-catenin was highly expressed by P7TP3 silencing, and restored by XAV939, an inhibitor of the Wnt/β-catenin signaling pathway. Finally, microRNA (miR)-182-5p suppressed the expression of target gene P7TP3 by directly interacting with the 3'-UTR region. Taken together, P7TP3, the direct target gene of miR-182-5p, inhibited HCC by regulating migration, invasion, adhesion, proliferation and cell cycle progression of liver cancer cell through the Wnt/β-catenin signaling pathway. These findings provide strong evidence that P7TP3 functions as a new promising tumor suppressor in HCC.

Response to oncogenic factors like UV, GADD45 family in skin participates in scavenging ROS, DNA repair and cell cycle control. Because of this, the previous study of the chronic UVB injury model has found that hsa-miR-300 can conduct intercellular transport by exosomes and target regulation of GADD45B. Whether the hsa-miR-300-GADD45B still regulates tumor development by cell cycle pathway is unclear. Through transcriptomic analysis of primary (n=39) and metastatic (n=102) melanoma, it was confirmed that in metastatic samples, some of the 97 down-regulated genes participate in maintaining skin homeostasis while 42 up-regulated genes were enriched in cancer-related functions. Furthermore, CDKN1A, CDKN2A, CXCR4 and RAD51 in the melanoma pathway, were also differentially expressed between normal skin and melanoma. CDKN1A and CDKN2A were also found to be involved in TP53-dependent cell cycle regulation. In conclusion, it was speculated that CDKN1A, CDKN2A, TP53, GADD45B and hsa-miR-300 may have regulatory relationships. It was demonstrated that there is a bidirectional regulation between hsa-miR-300 and TP53. In addition, miR-300 can regulate CDKN1A by GADD45B/TP53 and promote melanoma growth by accelerating the cell cycle transition from G1/S to G2 phase.