Mechanical tension mobilizes Lgr6 epidermal stem cells to drive skin growth.

Uniquely among mammalian organs, skin is capable of marked size change in adults, yet the mechanisms underlying this notable capacity are unclear. Here, we use a system of controlled tissue expansion in mice to uncover cellular and molecular determinants of skin growth. Through machine learning-guided three-dimensional tissue reconstruction, we capture morphometric changes in growing skin.

Bacteria induce skin regeneration via IL-1β signaling.

Environmental factors that enhance regeneration are largely unknown. The immune system and microbiome are attributed roles in repairing and regenerating structure but their precise interplay is unclear. Here, we assessed the function of skin bacteria in wound healing and wound-induced hair follicle neogenesis (WIHN), a rare adult organogenesis model.

miR-17 promotes expansion and adhesion of human cord blood CD34(+) cells in vitro.

Introduction: We have recently found that miR-17 is necessary in the cell-extrinsic control of cord blood (CB) CD34(+) cell function. Here, we demonstrated that the proper level of miR-17 is also necessary in the cell-intrinsic control of the hematopoietic properties of CB CD34(+) cells.

Methods: The miR-17 overexpression and knockdown models were created using primary CB CD34(+) cells transfected by the indicated vectors.

MicroRNA-146a feedback suppresses T cell immune function by targeting Stat1 in patients with chronic hepatitis B.

More than 350 million people are chronically infected with hepatitis B virus, and dysfunctional T cell responses contribute to persistent viral infection and immunopathogenesis in chronic hepatitis B (CHB). However, the underlying mechanisms of T cell hyporesponsiveness remain largely undefined. Given the important role of microRNA-146a (miR-146a) in diverse aspects of lymphocyte function, we investigated the potential role and mechanism of miR-146a in regulating T cell immune responses in CHB.

Hepatitis B virus mRNA-mediated miR-122 inhibition upregulates PTTG1-binding protein, which promotes hepatocellular carcinoma tumor growth and cell invasion.

As the most abundant liver-specific microRNA, miR-122 is involved in diverse aspects of hepatic function and neoplastic transformation. Our previous study showed that miR-122 levels are significantly decreased in hepatitis B virus (HBV)-infected patients, which may facilitate viral replication and persistence (S. Wang, L.

Inhibition of alpha interferon (IFN-α)-induced microRNA-122 negatively affects the anti-hepatitis B virus efficiency of IFN-α.

Alpha interferon (IFN-α)-based therapy can effectively treat chronic hepatitis B virus (HBV) infection, which causes life-threatening complications. Responses to IFN-α therapy vary greatly in chronic hepatitis B (CHB) patients, but underlying mechanisms are almost unknown. In this study, we found that IFN-α treatment induced a marked decrease of microRNA-122 (miR-122) expression in hepatocytes.

[Immune activity of heat shock protein gp96 and its application in active immunotherapy for tumor and infectious diseases].

Heat-shock protein gp96 associates with antigenic peptides derived from tumor and virus. Exogenous gp96-peptide complexes are taken up by antigen-presenting cells through interaction with its receptor CD91 on the cell surface, and cross-present antigenic peptides to MHC class I molecules by a peptide relay line in the endoplasmic reticulum for specific T-cell activation. Meanwhile, gp96 has been shown to initiate innate immune responses through interaction with toll-like receptor 2 and toll-like receptor 4.

MiR-122 in hepatic function and liver diseases.

As the most abundant liver-specific microRNA, microRNA-122 (miR-122) is involved in various physiological processes in hepatic function as well as in liver pathology. There is now compelling evidence that miR-122, as a regulator of gene networks and pathways in hepatocytes, plays a central role in diverse aspects of hepatic function and in the progress of liver diseases. This liver-enriched transcription factors-regulated miRNA promotes differentiation of hepatocytes and regulates lipid metabolism.

Biological effects of decreasing RBM15 on chronic myelogenous leukemia cells.

RNA binding motif protein 15 (RBM15) was originally described as a 5' translocation partner of the MAL gene in t(1;22)(p13;q13)infant acute megakaryocytic leukemia. Although previous investigations have shown that Rbm15 has broad regulatory effects within murine hematopoiesis through modulating Notch-induced transcriptional activation, which plays key roles in leukemogenesis, it is not clear what the functions of RBM15 are in the regulation of hematological malignancies. In the present study, we show that RBM15 expression was significantly increased in patients with blast-crisis chronic myelogenous leukemia (CML) compared with chronic-phase or accelerated-phase disease by real-time reverse transcription-polymerase chain reaction (RT-PCR) assay.

Loss of microRNA 122 expression in patients with hepatitis B enhances hepatitis B virus replication through cyclin G(1) -modulated P53 activity.

Unlabelled: Hepatitis B virus (HBV) causes chronic infection in about 350 million people worldwide. Given the important role of the most abundant liver-specific microRNA, miR-122, in hepatic function and liver pathology, here we investigated the potential role and mechanism of miR-122 in regulating HBV replication. We found that miR-122 expression in liver was significantly down-regulated in patients with HBV infection compared with healthy controls, and the miR-122 levels were negatively correlated with intrahepatic viral load and hepatic necroinflammation.

[Enhancement of cellular and humoral immune responses of HBV DNA vaccine by HSP70 and gp96].

While currently therapeutic vaccines for chronic hepatitis B virus (HBV) infection are actively being developed to complement standard antiviral treatments, their immune activity, especially T cell activity, remains to be further improved. Here, we investigated the role of heat shock proteins HSP70 and gp96 on cellular and humoral immunity, using the main structure antigens of hepatitis core (HBcAg) and surface (HBsAg) as the DNA vaccine. By ELISPOT (enzyme linked immunospot assay), IFN-gamma intracellular staining, [3H]-thymidine incorporation and ELISA (enzyme linked immunosorbent assay) analyses, we showed that immunization with HBsAg/HBcAg DNA formulation along with HSP70 or gp96 induced significant increase of T-cell (about 1-6-fold) and antibody (about 20%-60%) immunity against HBsAg and HBcAg.

Regulatory T-cell depletion synergizes with gp96-mediated cellular responses and antitumor activity.

Despite its potent immunostimulatory properties, vaccination with autologous tumor-derived gp96 has relatively modest antitumor effect in a range of clinical trials. Based on our previous study showing a gp96-mediated immune balance between CTL and Tregs, here we investigated possible synergy between gp96 vaccine and systemic Treg depletion on induction of antitumor T-cell immunity and the mechanisms accounting for synergistic efficacy. In gp96-peptide complex immunized BALB/c mice, anti-CD25 mAb treatment significantly increased IFN-γ-producing CD8(+) and CD4(+) T cells by about 1-2-fold in spleen and 40-50% in lymph node.

Heat shock protein gp96 enhances humoral and T cell responses, decreases Treg frequency and potentiates the anti-HBV activity in BALB/c and transgenic mice.

More than 350 million people worldwide are chronically infected with hepatitis B virus (HBV). Broad repertoire and strong magnitude of HBV-specific T cell responses are thought to play key roles for virus control and clearance. Previous studies together with ours showed that heat shock protein gp96 as adjuvant induces antigen specific T cell responses, yet little is known for its anti-viral properties.

Hansenula polymorpha expressed heat shock protein gp96 exerts potent T cell activation activity as an adjuvant.

Previous studies together with ours showed that heat shock protein gp96 as an adjuvant induces antigen specific T cell responses against cancer and infectious diseases. However, at present there is no efficient method to obtain high amount of full-length gp96 by in vitro expression. Here, we used the yeast Hansenula polymorpha as an efficient host for gp96 recombinant protein production.