Synthesis and evaluation of nitrogen-containing derivatives of 3,11-dioxo-olean-12-en-30-oic acid against HIV-1 protease.

Thirteen nitrogen-containing derivatives of 3,11-dioxo-olean-12-en-30-oic acid were synthesised by introducing various amino acids and nitrogen-containing heterocyclic groups at the 30-carboxyl group, starting from 18-glycyrrhetinic acid. Among the 13 derivatives, 10 exhibited inhibitory activity against HIV-1 PR, with IC values ranging from 0.19 to 0.

Adsorption Behaviour of Reactive Blue 194 on Raw Ramie Yarn in Palm Oil and Water Media.

As an edible oil, palm oil is also safe and reliable in dyeing, and the residual palm oil after dyeing can be recycled and used continuously, which is green and environmentally friendly and has great research prospects. In this research, raw ramie yarn, used for traditional grass cloth, was dyed in a palm oil medium using Reactive Blue 194. Studying the adsorption and diffusion behaviour in the dyeing process is necessary.

Sustainable and eco-friendly dyeing of traditional grass cloth with a reactive dye in palm oil medium.

Traditional grass cloth has been used in China for a long time for the manufacturing of various household furnishing textiles and ladieswear. However, traditionally the grass cloth is dyed with reactive dyes in an aqueous medium, but the dyeing process is not sustainable because of high energy and water usage and the production of coloured effluent. In this work, the possibility of palm oil/water dual-phase dyeing of traditional grass cloth with a reactive dye, C.

A Dual Inhibitor of DYRK1A and GSK3β for β-Cell Proliferation: Aminopyrazine Derivative GNF4877.

Loss of β-cell mass and function can lead to insufficient insulin levels and ultimately to hyperglycemia and diabetes mellitus. The mainstream treatment approach involves regulation of insulin levels; however, approaches intended to increase β-cell mass are less developed. Promoting β-cell proliferation with low-molecular-weight inhibitors of dual-specificity tyrosine-regulated kinase 1A (DYRK1A) offers the potential to treat diabetes with oral therapies by restoring β-cell mass, insulin content and glycemic control.

Selective DYRK1A Inhibitor for the Treatment of Type 1 Diabetes: Discovery of 6-Azaindole Derivative GNF2133.

Autoimmune deficiency and destruction in either β-cell mass or function can cause insufficient insulin levels and, as a result, hyperglycemia and diabetes. Thus, promoting β-cell proliferation could be one approach toward diabetes intervention. In this report we describe the discovery of a potent and selective DYRK1A inhibitor GNF2133, which was identified through optimization of a 6-azaindole screening hit.

Inhibition of DYRK1A and GSK3B induces human β-cell proliferation.

Insufficient pancreatic β-cell mass or function results in diabetes mellitus. While significant progress has been made in regulating insulin secretion from β-cells in diabetic patients, no pharmacological agents have been described that increase β-cell replication in humans. Here we report aminopyrazine compounds that stimulate robust β-cell proliferation in adult primary islets, most likely as a result of combined inhibition of DYRK1A and GSK3B.

Small-molecule inducer of β cell proliferation identified by high-throughput screening.

The identification of factors that promote β cell proliferation could ultimately move type 1 diabetes treatment away from insulin injection therapy and toward a cure. We have performed high-throughput, cell-based screens using rodent β cell lines to identify molecules that induce proliferation of β cells. Herein we report the discovery and characterization of WS6, a novel small molecule that promotes β cell proliferation in rodent and human primary islets.

Epithelial progenitor 1, a novel factor associated with epithelial cell growth and differentiation.

The growth and renewal of epithelial tissue is a highly orchestrated and tightly regulated process occurring in different tissue types under a variety of circumstances. We have been studying the process of pancreatic regeneration in mice. We have identified a cell surface protein, named EP1, which is expressed on the duct epithelium during pancreatic regeneration.

[Prosthetic treatment of blow-out fracture in medial orbital wall with nasoseptal cartilage under nasal endoscope].

Objective: To study the clinical effect of Treatment of blow-out fracture of medial orbital wall with nasoseptal cartilage under nasal endoscope.

Method: Under a nasal endoscope, the fracture and the prolapsed orbital contents were reduced to the orbit, and then an autogenous nasoseptal cartilage was grafted into the orbital defect. The variations in the visual acuity, diplopia, enophthalmos degree and eyeball position were detected preoperatively and postoperatively.

Upregulation of activin signaling in experimental colitis.

Several lines of studies have suggested that activins are critical mediators of inflammation and tissue repair. As activins and their receptors are expressed in the gastrointestinal tract, we tested the hypothesis that activin signaling is involved in the development of colitis by using two murine models of colitis induced by dextran sodium sulfate (DSS) or in mdr1a-/- mice. By immunohistochemistry, expression of activins was found increased in both models and correlated with the severity of inflammation.

Nodal and lefty signaling regulates the growth of pancreatic cells.

Nodal and its antagonist, Lefty, are important mediators specifying the laterality of the organs during embryogenesis. Nodal signals through activin receptors in the presence of its co-receptor, Cripto. In the present study, we investigated the possible roles of Nodal and Lefty signaling during islet development and regeneration.

FGFR3 is a negative regulator of the expansion of pancreatic epithelial cells.

Fibroblast growth factors (FGFs) and their receptors (FGFRs) are key signaling molecules for pancreas development. Although FGFR3 is a crucial developmental gene, acting as a negative regulator of bone formation, its participation remains unexplored in pancreatic organogenesis. We found that FGFR3 was expressed in the epithelia in both mouse embryonic and adult regenerating pancreata but was absent in normal adult islets.

PYY in the expanding pancreatic epithelium.

Gut peptide YY (PYY) plays an important role in regulating metabolism and is expressed during the ontogeny of the pancreas. However, its biological role during endocrine cell formation is not fully understood, and its role, if any, during pancreatic regeneration in the adult has not yet been explored. The knowledge of factors involved in beta cell renewal in adult animals is clearly relevant for the design of treatment strategies for type 1 diabetes.

BMP4 regulates pancreatic progenitor cell expansion through Id2.

Inhibitor of DNA binding (Id) proteins bind to and inhibit the function of basic helix-loop-helix (bHLH) transcription factors including those that regulate pancreatic development. Moreover, bone morphogenetic proteins (BMPs) regulate the expression of Ids. We hypothesized that BMP4 and Id proteins play a role in the expansion and differentiation of epithelial progenitor cells.

Identification and expansion of pancreatic stem/progenitor cells.

Pancreatic islet transplantation represents an attractive approach for the treatment of diabetes. However, the limited availability of donor islets has largely hampered this approach. In this respect, the use of alternative sources of islets such as the ex vivo expansion and differentiation of functional endocrine cells for treating diabetes has become the major focus of diabetes research.

Inhibition of activin signaling induces pancreatic epithelial cell expansion and diminishes terminal differentiation of pancreatic beta-cells.

Activins regulate the growth and differentiation of a variety of cells. During pancreatic islet development, activins are required for the specialization of pancreatic precursors from the gut endoderm during midgestation. In this study, we probed the role of activin signaling during pancreatic islet cell development and regeneration.

Assessment of the function of the betaC-subunit of activin in cultured hepatocytes.

We assessed the function of the beta(C)-subunit of activin in hepatocytes. We studied the effect of conditioned medium of Chinese hamster ovary (CHO) cell line stably expressing the beta(C) gene (CHO-beta(C)) on growth of AML12 hepatocytes. We also examined the effect of recombinant activin C and transfection of the beta(C) gene by using adenovirus vector.

The stromal cell-derived factor-1alpha/CXCR4 ligand-receptor axis is critical for progenitor survival and migration in the pancreas.

The SDF-1alpha/CXCR4 ligand/chemokine receptor pair is required for appropriate patterning during ontogeny and stimulates the growth and differentiation of critical cell types. Here, we demonstrate SDF-1alpha and CXCR4 expression in fetal pancreas. We have found that SDF-1alpha and its receptor CXCR4 are expressed in islets, also CXCR4 is expressed in and around the proliferating duct epithelium of the regenerating pancreas of the interferon (IFN) gamma-nonobese diabetic mouse.

Development of cell markers for the identification and expansion of islet progenitor cells.

Diabetes mellitus results from the anatomical or functional loss of insulin-producing beta cells of the pancreas. Despite significant advances in current treatment, patients with diabetes still do not maintain optimal glucose levels and therefore face debilitating complications such as hypoglycemia, retinopathy or cardiovascular diseases later in life. Islet transplantation therefore holds great promise as an ultimate cure for diabetes.

Up-regulation of the expression of activins in the pancreatic duct by reduction of the beta-cell mass.

Activins expressed in progenitor cells of the pancreas regulate differentiation of endocrine cells during development. Neogenesis of beta-cells takes place in adult animals under some conditions, and beta-cells are thought to arise from precursors locating in the pancreatic duct. In the present study, we investigated whether or not activins are expressed in the duct where beta-cell neogenesis is initiated.

Involvement of the activin-follistatin system in tubular regeneration after renal ischemia in rats.

This study was conducted to investigate the involvement of the activin-follistatin system in renal regeneration after ischemic injury. Expression of mRNA for the activin beta(A) subunit was not detected in normal kidneys but increased markedly after renal ischemia. Immunoreactive beta(A) subunit was detected in tubular cells of the outer medulla in ischemic but not normal kidneys.