Nsun2 coupling with RoRγt shapes the fate of Th17 cells and promotes colitis.

T helper 17 (Th17) cells are a subset of CD4 T helper cells involved in the inflammatory response in autoimmunity. Th17 cells secrete Th17 specific cytokines, such as IL-17A and IL17-F, which are governed by the master transcription factor RoRγt. However, the epigenetic mechanism regulating Th17 cell function is still not fully understood.

Targeted therapy of atherosclerosis by pH-sensitive hyaluronic acid nanoparticles co-delivering all-trans retinal and rapamycin.

Atherosclerosis, the leading cause of death in the elderly worldwide, is typically characterized by elevated reactive oxygen species (ROS) levels and a chronic inflammatory state at the arterial plaques. Herein, pH-sensitive nanoparticles (HR NPs) co-delivering all-trans retinal (ATR), an antioxidant linked to hyaluronic acid (HA) through a pH-sensitive hydrazone bond, and rapamycin (RAP), an anti-atherosclerotic drug loaded into the nanoparticle core, are developed for targeted combination therapy of atherosclerosis. In this way, HR NPs might simultaneously reduce ROS levels ATR antioxidant activity and reduce inflammation the anti-inflammatory effect of RAP.

Vagal-α7nAChR signaling is required for lung anti-inflammatory responses and arginase 1 expression during an influenza infection.

Vagal circuit-α7 nicotinic acetylcholine receptor (α7nAChR, coded by Chrna7) signaling can modulate lung proinflammatory responses. Arginase 1 (ARG1) plays a crucial role in the resolution of lung inflammation. However, whether vagal-α7nAChR signaling can regulate lung inflammation and ARG1 expression during an influenza infection is elusive.

PDK1 Regulates the Maintenance of Cell Body and the Development of Dendrites of Purkinje Cells by pS6 and PKCγ.

3-Phosphoinositide-dependent protein kinase-1 (PDK1) plays a critical role in the development of mammalian brain. Here, we investigated the role of PDK1 in Purkinje cells (PCs) by generating the PDK1-conditional knock-out mice (cKO) through crossing or mice with mice. The male mice were used in the behavioral testing, and the other experiments were performed on mice of both sexes.

Antagonizing miR-7 suppresses B cell hyperresponsiveness and inhibits lupus development.

Objectives: The objective of this study was to address the biological function of miR-7 in an animal model of systemic lupus erythematosus.

Methods: MRL lupus mice were administrated antagomiR-7 or a scramble control by tail vein for 5weeks. Three groups of animals' tissues were assessed for lupus manifestations by immunofluorescence and immunohistochemistry, and serum was examined for levels of autoantibodies and inflammatory cytokines.

The efficacy and safety of antithrombotic therapy in patients with positive antiphospholipid antibodies receiving invasive procedures: experience from a single tertiary center.

Objectives: To evaluate the efficacy and safety of antithrombotic prophylaxis and to explore potential risk factors for thrombotic/bleeding events in patients with positive antiphospholipid (aPL) antibodies receiving invasive procedures.

Method: All aPL-positive patients who underwent invasive procedures in Peking Union Medical College Hospital, from January 2002 to April 2018, were retrospectively enrolled. Demographic features, clinical features, antiphospholipid antibody profiles, types of invasive procedures, and antithrombotic management, as well as complications and outcomes, were systematically reviewed and recorded.

Comparison of the impact of Tripterygium wilfordii Hook F and Methotrexate treatment on radiological progression in active rheumatoid arthritis: 2-year follow up of a randomized, non-blinded, controlled study.

Background: Tripterygium wilfordii Hook F (TwHF) alone or in combination with methotrexate (MTX) has been shown to be more effective than MTX monotherapy in controlling the manifestations in subjects with disease-modifying antirheumatic drug (DMARD)-naïve active rheumatoid arthritis (RA) over a 6-month period. The long-term impact of these therapies on disease activity and radiographic progression in RA has not been examined.

Methods: Patients with DMARD-naïve RA enrolled in the "Comparison of Tripterygium wilfordii Hook F with methotrexate in the Treatment of Active Rheumatoid Arthritis" (TRIFRA) study were randomly allocated into three arms with TwHF or MTX or the two in combination.

NDR Kinases Are Essential for Somitogenesis and Cardiac Looping during Mouse Embryonic Development.

Studies of mammalian tissue culture cells indicate that the conserved and distinct NDR isoforms, NDR1 and NDR2, play essential cell biological roles. However, mice lacking either Ndr1 or Ndr2 alone develop normally. Here, we studied the physiological consequences of inactivating both NDR1 and NDR2 in mice, showing that the lack of both Ndr1/Ndr2 (called Ndr1/2-double null mutants) causes embryonic lethality.

Akt-p53-miR-365-cyclin D1/cdc25A axis contributes to gastric tumorigenesis induced by PTEN deficiency.

Although PTEN/Akt signaling is frequently deregulated in human gastric cancers, the in vivo causal link between its dysregulation and gastric tumorigenesis has not been established. Here we show that inactivation of PTEN in mouse gastric epithelium initiates spontaneous carcinogenesis with complete penetrance by 2 months of age. Mechanistically, activation of Akt suppresses the abundance of p53, leading to decreased transcription of miR-365, thus causing upregulation of cyclin D1 and cdc25A, which promotes gastric cell proliferation.

FSH acts on the proliferation of type A spermatogonia via Nur77 that increases GDNF expression in the Sertoli cells.

The molecular mechanism responsible for the regulation of GDNF in Sertoli cells remains largely unknown. In the present study, FSH induced the expression of Nur77 and GDNF in mouse testis tissue and human fetal Sertoli cells. Moreover, FSH increased the number of A spermatogonia co-cultured with Sertoli cells.

PDK1 plays a critical role in regulating cardiac function in mice and human.

Background: PDK1 is an essential protein kinase that plays a critical role in mammalian development. Mouse lacking PDK1 leads to multiple abnormalities and embryonic lethality at E9.5.

[Changes of MAPK and Akt signaling pathways in hearts and placentas of aborted fetuses with congenital heart disease].

Objective: To study the changes of MAPK and Akt signaling pathways in hearts and placentas of aborted fetuses with congenital heart disease (CHD), and investigate their roles in the pathogenesis of CHD.

Methods: Ten aborted fetuses with severe CHD (CHD group) and 7 gestational age-matched non-cardiac malformation aborted fetuses (control group) were enrolled. Western blot analysis was undertaken to assess the expression of p38, p38alpha, p-p38, MEF2, ERK, p-ERK, Akt, p-Akt(Ser473) and p-Akt(Thr308) in left ventricles and placentas of the fetuses, while semi-quantitative reverse transcription polymerase chain reaction analysis was used to detect the expression of p38alpha isoforms mRNA in hearts.

Life with a single isoform of Akt: mice lacking Akt2 and Akt3 are viable but display impaired glucose homeostasis and growth deficiencies.

To address the issues of isoform redundancy and isoform specificity of the Akt family of protein kinases in vivo, we generated mice deficient in both Akt2 and Akt3. In these mice, only the Akt1 isoform remains to perform essential Akt functions, such as glucose homeostasis, proliferation, differentiation, and early development. Surprisingly, we found that Akt2(-/-) Akt3(-/-) and even Akt1(+/-) Akt2(-/-) Akt3(-/-) mice developed normally and survived with minimal dysfunctions, despite a dramatic reduction of total Akt levels in all tissues.

PKBalpha is required for adipose differentiation of mouse embryonic fibroblasts.

Protein kinase Balpha (PKBalpha) is a key regulator of metabolism, proliferation and differentiation. We have explored the role of PKBalpha in adipogenesis using wild-type and PKBalpha-knockout mouse embryonic fibroblasts (MEFs) and show that lack of PKBalpha prevents MEF differentiation into adipocytes. Expression of ectopic PKBalpha in PKBalpha-deficient cells restores adipogenesis.

Dosage-dependent effects of Akt1/protein kinase Balpha (PKBalpha) and Akt3/PKBgamma on thymus, skin, and cardiovascular and nervous system development in mice.

Akt/protein kinase B (PKB) plays a critical role in the regulation of metabolism, transcription, cell migration, cell cycle progression, and cell survival. The existence of viable knockout mice for each of the three isoforms suggests functional redundancy. We generated mice with combined mutant alleles of Akt1 and Akt3 to study their effects on mouse development.

Essential role of protein kinase B gamma (PKB gamma/Akt3) in postnatal brain development but not in glucose homeostasis.

Protein kinase B is implicated in many crucial cellular processes, such as metabolism, apoptosis and cell proliferation. In contrast to Pkb(alpha) and Pkb(beta)-deficient mice, Pkb(gamma)(-/-) mice are viable, show no growth retardation and display normal glucose metabolism. However, in adult Pkb(gamma)mutant mice, brain size and weight are dramatically reduced by about 25%.

Identification and modulation of a caveolae-dependent signal pathway that regulates plasminogen activator inhibitor-1 in insulin-resistant adipocytes.

Plasminogen activator inhibitor-1 (PAI-1) plays an important role in the pathogenesis of obesity-driven type 2 diabetes mellitus and associated cardiovascular complications. Here, we show that perturbation of caveolar microdomains leads to insulin resistance and concomitant up-regulation of PAI-1 in 3T3L1 adipocytes. We present several lines of evidence showing that the phosphatidylinositol 3-kinase (PI3K) pathway negatively regulates PAI-1 gene expression.

Protein kinase B alpha/Akt1 regulates placental development and fetal growth.

Protein kinase B alpha (PKB alpha/Akt1) is implicated in the regulation of metabolism, transcription, cell survival, angiogenesis, cell migration, growth, and tumorigenesis. Previously, it was reported that PKB alpha-deficient mice are small with increased neonatal mortality (Cho, H., Thorvaldsen, J.