Menin-regulated Pbk controls high fat diet-induced compensatory beta cell proliferation.

Pancreatic beta cells undergo compensatory proliferation in the early phase of type 2 diabetes. While pathways such as FoxM1 are involved in regulating compensatory beta cell proliferation, given the lack of therapeutics effectively targeting beta cell proliferation, other targetable pathways need to be identified. Herein, we show that Pbk, a serine/threonine protein kinase, is essential for high fat diet (HFD)-induced beta cell proliferation in vivo using a Pbk kinase deficiency knock-in mouse model.

Protective Effect of Iridoid Glycosides of the Leaves of Syringa oblata Lindl. on Dextran Sulfate Sodium-Induced Ulcerative Colitis by Inhibition of the TLR2/4/MyD88/NF-B Signaling Pathway.

Iridoid glycoside (IG) is the major active fraction extracted from the leaves of . In view of its antimicrobial and antidiarrheal potential, it could be beneficial for the treatment of ulcerative colitis (UC). In the present study, IG (20, 40, and 80 mg/kg) was administered orally for 14 days to dextran sulfate sodium- (DSS-) induced colitis rats.

Neutrophil-mediated and low density lipoprotein receptor-mediated dual-targeting nanoformulation enhances brain accumulation of scutellarin and exerts neuroprotective effects against ischemic stroke.

Delivery of poorly permeable drugs across the blood-brain barrier (BBB) is a great challenge in the treatment of ischemic stroke. In order to construct a suitable delivery system for this purpose, we developed a dual-targeting nanoformulation to transfer therapeutic agents targeting the inflammatory sites of the ischemic brain. The matrix of this system is a hydroxyl-terminated polyamidoamine dendrimer with excellent biodegradability.

Kinase inhibitors of HER2/AKT pathway induce ERK phosphorylation via a FOXO-dependent feedback loop.

Inhibitors of the HER2/PI3K/AKT pathway are being developed, and shown promise in clinical trials for various types of cancers. However, development of drug resistance is a challenging problem for therapy. Elucidating various adaptive pathways leading to resistance or reduced sensitivity to drugs targeting the HER2/PI3K/AKT pathway may provide new insights into countering the resistance.

BRD4 inhibitor IBET upregulates p27kip/cip protein stability in neuroendocrine tumor cells.

The prevalence of neuroendocrine tumors (NETs) has recently been increasing. Although various drugs such as Octreotide and its analogs show certain efficacy, NETs in many patients progress and metastasize. It is desirable to develop new interventions to improve the therapy.

Menin and Daxx Interact to Suppress Neuroendocrine Tumors through Epigenetic Control of the Membrane Metallo-Endopeptidase.

Neuroendocrine tumors (NET) often harbor loss-of-function mutations in the MEN1 and DAXX tumor suppressor genes. Here, we report that the products of these genes, menin and Daxx, interact directly with each other to suppress the proliferation of NET cells, to a large degree by inhibiting expression of the membrane metallo-endopeptidase (MME). Menin and Daxx were required to enhance histone H3 lysine9 trimethylation (H3K9me3) at the MME promoter, as mediated partly by the histone H3 methyltransferase SUV39H1.

The effect of cationic albumin-conjugated PEGylated tanshinone IIA nanoparticles on neuronal signal pathways and neuroprotection in cerebral ischemia.

Targeted treatment of ischemic stroke remains problem due to the complex pathogenesis of this disease and the difficulty in drug delivery across the blood-brain barrier (BBB). In the present study, the delivery efficiency of cationic bovine serum albumin-conjugated tanshinone IIA PEGylated nanoparticles (CBSA-PEG-TIIA-NPs) in rat brain was investigated. We further explored whether the protective mechanism of CBSA-PEG-TIIA-NPs in cerebral ischemia was associated with modulating neuronal signaling pathways.

Protective effects of cationic bovine serum albumin-conjugated PEGylated tanshinone IIA nanoparticles on cerebral ischemia.

Tanshinone IIA is a good candidate for treating cerebral ischemia, but its short half-life and poor permeability across the blood-brain-barrier (BBB) limit its curative efficacy. In this study, we successfully developed cationic bovine serum albumin-conjugated tanshinone IIA PEGylated nanoparticles (CBSA-PEG-TIIA-NPs). A cerebral ischemia rat model was established to evaluate the treatment efficacy and protective mechanism of CBSA-PEG-TIIA-NPs.

Serum retinol-binding protein 4 is elevated and positively associated with insulin resistance in postmenopausal women.

Retinol-binding protein 4 (RBP4) is a newly discovered adipokine, which is reported to be correlated with insulin resistance (IR) and type 2 diabetes (T2DM). The aim of this study was to evaluate the influence of menopausal status on RBP4 concentration and to investigate serum RBP4 with IR and the prevalence of T2DM in postmenopausal women. We conducted a cross-sectional study and enrolled 34 healthy premenopausal women, 41 healthy postmenopausal women and 37 postmenopausal women with T2DM.

Effect of ScrF I polymorphism in the 2nd intron of the HMGCR gene on lipid-lowering response to simvastatin in Chinese diabetic patients.

Objective: To investigate whether ScrF I polymorphism in the 2nd intron of the HMG-COA reductase gene (HMGCR) influences serum lipid levels and whether this polymorphism affects the efficiency of the cholesterol lowering HMG-CoA reductase inhibitor, simvastatin.

Methods: One hundred sixty-eight patients with type 2 diabetes mellitus (T2DM) prospectively received simvastatin as a single-agent therapy (20mg day-1 p.o.