Quantitative Imaging of the Action of vCPP2319, an Antimicrobial Peptide from a Viral Scaffold, against Staphylococcus aureus Biofilms of a Clinical Isolate.

The formation of biofilms is a common virulence factor that makes bacterial infections difficult to treat and a major human health problem. Biofilms are bacterial communities embedded in a self-produced matrix of extracellular polymeric substances (EPS). In this work, we show that vCPP2319, a polycationic peptide derived from the capsid protein of Torque teno douroucouli virus, is active against preformed Staphylococcus aureus biofilms produced by both a reference strain and a clinical strain isolated from a diabetic foot infection, mainly by the killing of biofilm-embedded bacteria. The direct effect of vCPP2319 on bacterial cells was imaged using atomic force and confocal laser scanning microscopy, showing that the peptide induces morphological changes in bacterial cells and membrane disruption. Importantly, vCPP2319 exhibits low toxicity toward human cells and high stability in human serum. Since vCPP2319 has a limited effect on the biofilm EPS matrix itself, we explored a combined effect with α-amylase (EC 3.2.1.1), an EPS matrix-degrading enzyme. In fact, α-amylase decreases the density of S. aureus biofilms by 2.5-fold. Nonetheless, quantitative analysis of bioimaging data shows that vCPP2319 partially restores biofilm compactness after digestion of the polysaccharides, probably due to electrostatic cross-bridging of the matrix nucleic acids, which explains why α-amylase fails to improve the antibacterial action of the peptide.

Potential Roles of α-amylase in Alzheimer's Disease: Biomarker and Drug Target.

Alzheimer's disease (AD), the most common form of dementia, is pathologically characterized by the deposition of amyloid-ß plaques and the formation of neurofibrillary tangles. In a neurodegenerative brain, glucose metabolism is also impaired and considered as one of the key features in AD patients. The impairment causes a reduction in glucose transporters and the uptake of glucose as well as alterations in the specific activity of glycolytic enzymes. Recently, it has been reported that α-amylase, a polysaccharide-degrading enzyme, is present in the human brain. The enzyme is known to be associated with various diseases such as type 2 diabetes mellitus and hyperamylasaemia. With this information at hand, we hypothesize that α-amylase could have a vital role in the demented brains of AD patients. This review aims to shed insight into the possible link between the expression levels of α-amylase and AD. Lastly, we also cover the diverse role of amylase inhibitors and how they could serve as a therapeutic agent to manage or stop AD progression.

Amelioration of hyperglycaemia and modulation of pro-inflammatory cytokines by Tamarix gallica fractions in alloxan induced diabetic rats.

Present study is engrossed in identification of phyto-constituents from aerial part extracts of Tamarix gallica and appraisal of its anti-oxidant, anti-diabetic and anti-inflammatory potential based upon its folktale use. The methanol and n-hexane fractions of aerial parts were analysed using high performance liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS) respectively. Inhibitory concentration (IC50) showed better results in case of methanolic extract for both in antioxidant (IC50= 15.47 µg/mL) and alpha amylase (IC50=18.75 µg/mL) assays. Significantly higher quantities of phenolic and flavonoid contents were present in methanolic extract. A significant correlation was found to be existed between these contents and IC50 of antioxidant assay. Alloxan induced hyperglycaemia declined along with improvement in lipid profile, C-reactive proteins (CRP), liver function tests (LFTs) and renal function tests (RFTs). Methanolic fraction (500 mg/kg) was also related to significant reduction in levels of inflammatory markers i.e. tumour necrosis factor-alpha, TNF- α (1.28 ± 0.13 g/L) and interleukin-6, IL-6 (98 ± 10.4 pg/L) as observed in diabetic rats. Based upon the above findings, the study suggests that methanolic fraction from aerial parts of the T. gallica has better anti-diabetic profile which might be attributed to its alpha amylase, anti-oxidant and anti-inflammatory potential.

Glucose and pH Dual-Responsive Nanogels for Efficient Protein Delivery.

Direct delivery of protein suffers from their in vitro and in vivo instability, immunogenicity, and a relatively short half-life within the body. To overcome these challenges, pH and glucose dual-responsive biodegradable nanogels comprised of dextran and poly(L-glutamic acid)-g-methoxy poly-(ethylene glycol)/phenyl boronic acid (PLG-g-mPEG/PBA) are designed. The cross-linked network imparted drug-loading efficacy of α-amylase up to 55.6% and hyaluronidase up to 29.1%. In vitro protein release profiles reveal that the release of protein is highly dependent on the pH or glucose concentrations, that is, less amount of protein is released at pH 7.4 or healthy blood glucose level (1 mg mL-1 glucose), while quicker release of protein occurs at pH 5.5 or diabetic blood glucose level (above 3 mg mL-1 glucose). Circular dichroism spectra show that the secondary structure of released protein is maintained compared to naive protein. Overall, the nanogels have provided a simple and effective strategy to deliver protein.

Review: Management of postprandial diarrhea syndrome.

Unexpected, urgent, sometimes painful bowel movements after eating are common complaints among adults. Without a clear etiology, if pain is present and resolves with the movements, this is usually labeled "irritable bowel syndrome-diarrhea" based solely on symptoms. If this symptom-based approach is applied exclusively, it may lead physicians not to consider treatable conditions: celiac disease, or maldigestion due to bile acid malabsorption, pancreatic exocrine insufficiency, or an a-glucosidase (sucrase, glucoamylase, maltase, or isomaltase) deficiency. These conditions can be misdiagnosed as irritable bowel syndrome-diarrhea (or functional diarrhea, if pain is not present). Limited testing is currently available to confirm these conditions (antibody screens for celiac disease; fecal fat as a surrogate marker for pancreatic function). Therefore, empirical treatment with alpha amylase, pancreatic enzymes, or a bile acid-binding agent may simultaneously treat these patients and serve as a surrogate diagnostic test. This review will summarize the current evidence for bile acid malabsorption, and deficiencies of pancreatic enzymes or a-glucosidases as potential causes for postprandial diarrhea, and provide an algorithm for treatment options.

High prevalence of gastric trichobezoars (hair balls) in Wistar-Kyoto rats fed a semi-purified diet.

Gastric trichobezoars (hair balls) are frequently found in rabbits but are rarely reported in rats. Several Wistar-Kyoto rats fed a semi-purified diet developed anorexia and abdominal tenderness. Proteolysis therapy with fresh papaya and commercially prepared enzyme was attempted in these rats but was not successful. The prevalence of trichobezoars at necropsy was 100%. We conclude that semi-purified diets contribute to trichobezoar formation in rats, but proteolysis therapy is not effective in dissolving the trichobezoars.