Chemical toolbox to interrogate Heparanase-1 activity.

The development of a robust chemical toolbox to interrogate the activity of heparanase-1 (HPSE-1), an endo-β-d-glucuronidase and the only known enzyme that cleaves heparan sulfate (HS), has become critically important. The primary function of HPSE-1, cleaving HS side chains from heparan sulfate proteoglycans (HSPGs), regulates the integrity of the extracellular matrix (ECM) and the bioavailability of active, heparan sulfate-binding partners such as enzymes, growth factors, chemokines, and cytokines. HPSE-1 enzymatic activity is strictly regulated and has been found to play fundamental roles in pathophysiological processes.

A Fluorogenic Green Merocyanine-Based Probe to Detect Heparanase-1 Activity.

Heparanase-1 (HPSE-1), an endo-β-D-glucuronidase, is an extracellular matrix (ECM) remodeling enzyme that degrades heparan sulfate (HS) chains of heparan sulfate proteoglycans (HSPGs). HPSE-1 functions to remodel the ECM and thereby disseminate cells, liberate HS-bound bioactive molecules, and release biologically active HS fragments. Being the only known enzyme for the cleavage of HS, HPSE-1 regulates a number of fundamental cellular processes including cell migration, cytokine regulation, angiogenesis, and wound healing.

Short-Term Decreasing and Increasing Dietary BCAA Have Similar, but Not Identical Effects on Lipid and Glucose Metabolism in Lean Mice.

Branched-chain amino acids (BCAA) showed multiple functions in glycolipid metabolism and protein synthesis. However, the impacts on the metabolic health of low or high dietary BCAA remain controversial due to the various experimental conditions. Gradient levels of BCAA were supplemented in lean mice for four weeks: 0BCAA (without BCAA), 1/2BCAA (half BCAA), 1BCAA (regular BCAA), and 2BCAA (double BCAA).

A Universal and Modular Scaffold for Heparanase Activatable Probes and Drugs.

Heparanase (HPSE) is an endo-β-glucuronidase involved in extracellular matrix remodeling in rapidly healing tissues, most cancers and inflammation, and viral infection. Its importance as a therapeutic target warrants further study, but such is hampered by a lack of research tools. To expand the toolkits for probing HPSE enzymatic activity, we report the design of a substrate scaffold for HPSE comprised of a disaccharide substrate appended with a linker, capable of carrying cargo until being cleaved by HPSE.

Threonine supplementation prevents the development of fat deposition in mice fed a high-fat diet.

Obesity is the main factor involved in the onset of many diseases. Threonine supplementation has been demonstrated to reduce fat mass and serum triglycerides in already obese mice. However, it is unclear whether threonine could inhibit the development of obesity in mice without previous high-fat diet induction.

Leucine, but not isoleucine or valine, affects serum lipid profiles and browning of WAT in mice.

Branched chain amino acids (BCAA), especially leucine (Leu), have been reported to decrease fat deposition. However, opposite effects of BCAA on lipid metabolism have been observed. To determine the role of BCAA in lipid metabolism, an amino acid-defined diet was formulated and C57BL/6J mice were assigned into the following groups: amino acid-defined control diet and control diet supplemented with Leu, isoleucine, or valine.

Valine Supplementation Does Not Reduce Lipid Accumulation and Improve Insulin Sensitivity in Mice Fed High-Fat Diet.

Branched-chain amino acids (BCAAs), particularly leucine, were reported to decrease obesity and relevant metabolic syndrome. However, whether valine has a similar effect has rarely been investigated. In the present study, mice were assigned into four treatments ( = 10): chow diet supplemented with water (CW) or valine (CV) and high-fat diet supplemented with water (HW) or valine (HV).

Dietary supplementation with aromatic amino acids decreased triglycerides and alleviated hepatic steatosis by stimulating bile acid synthesis in mice.

Emerging evidence shows that amino acids can modulate lipid metabolism. Aromatic amino acids (AAAs) serve as important precursors of several neurotransmitters and metabolic regulators that play a vital role in regulating nutrient metabolism. But whether AAAs have a lipid-lowering function remains unknown.

Splitting failure in side walls of a large-scale underground cavern group: a numerical modelling and a field study.

Vertical splitting cracks often appear in side walls of large-scale underground caverns during excavations owing to the brittle characteristics of surrounding rock mass, especially under the conditions of high in situ stress and great overburden depth. This phenomenon greatly affects the integral safety and stability of the underground caverns. In this paper, a transverse isotropic constitutive model and a splitting failure criterion are simultaneously proposed and secondly programmed in FLAC3D to numerically simulate the integral stability of the underground caverns during excavations in Dagangshan hydropower station in Sichuan province, China.