Systemic administration of a novel Beclin 1-derived peptide significantly upregulates autophagy in the spinal motor neurons of autophagy reporter mice.

Autophagy, an intracellular degradation system, plays a vital role in protecting cells by clearing damaged organelles, pathogens, and protein aggregates. Autophagy upregulation through pharmacological interventions has gained significant attention as a potential therapeutic avenue for proteinopathies. Here, we report the development of an autophagy-inducing peptide (BCN4) derived from the Beclin 1 protein, the master regulator of autophagy.

Human protozoa infection and dysplasia in ulcerative colitis: a neglected aspect in a prominent disease.

The chance of getting colorectal cancer (CRC) is higher in people with chronic ulcerative colitis (UC). The impact of parasitic infections on UC is underappreciated. The purpose of this study was to look into the effect of intestinal protozoal infections on the dysplastic changes generated by UC.

Toxoplasma gondii Suppresses Th2-Induced by Infection and Downregulates Serine Protease Genes Expression: A Critical Role in Vaccine Development.

Background: coinfection can modify host immune responses and the severity and spread of other parasites. We investigated how and infections counter-regulate each other's immune responses.

Methods: The parasite burden, the expression of rhoptry kinase ROP18 and putative serine protease (TsSP), the IgG1 and IgG2a responses, besides histopathological and immunohistochemical staining with iNOS and arginase were used to evaluate the dynamics of coinfection.

Comparative evaluation of the efficacy of topical tacrolimus 0.03% and topical calcipotriol 0.005% mixed with betamethasone dipropionate versus topical clobetasol 0.05% in treatment of alopecia areata: A clinical and trichoscopic study.

Background: Alopecia areata (AA) is a common non-scarring hair loss disorder that affects children and adults with a great psychological burden because of its recurrent and sometimes treatment-refractory nature.

Objective: To compare the efficacy of topical calcineurin inhibitor, topical potent steroid combined with vitamin D analogue versus topical superpotent steroid in treatment of localized AA.

Patients And Methods: Sixty subjects with chronic (>1 year) localized (SALT score < 25%) AA, confirmed clinically and dermoscopically, were randomized into three groups.

Mitigation of -induced ileitis by infection pinpointing immunomodulation.

The current study sought to investigate the potential role of infection in the treatment of -induced ileitis. Forty male Swiss albino mice were divided into four groups:a normal control group Igiven only phosphate-buffered saline (PBS), Group II givenPBS for 28 days then infected with cysts for the induction of gastroenteritis, Group III infected only with larvae, and Group IV concurrently infected with larvae, then 28 days post infection, enteritis was induced by oral inoculation with cysts. Histopathologicaland immunohistochemicalassessmentswere performed to determine the levels of inflammatory markers nuclear factor- κB (NF-κB) and myeloperoxidase in the ileum samples.

Finite element modeling of the breakage behavior of agricultural biomass pellets under different heights during handling and storage.

It is very important to determine the amount of mechanical damage to biomass pellets during handling, transportation, and storage. However, it is difficult to determine the amount of damage to biomass pellets caused by existing external forces. However, a useful method is the finite element methods, which can be used in different engineering fields to simulate the posture of the material under defined boundary conditions.

Probing Protein Solubility Patterns with Proteomics for Insight into Network Dynamics.

Proteome solubility contains latent information on the nature of protein interaction networks in cells and changes in solubility can provide information on rewiring of networks. Here, we report a simple one-step ultracentrifugation method to separate the soluble and insoluble fraction of the proteome. The method involves quantitative proteomics and a bioinformatics strategy to analyze the changes that arise.

Immiscible inclusion bodies formed by polyglutamine and poly(glycine-alanine) are enriched with distinct proteomes but converge in proteins that are risk factors for disease and involved in protein degradation.

Poly(glycine-alanine) (polyGA) is one of the polydipeptides expressed in Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 1 caused by C9ORF72 mutations and accumulates as inclusion bodies in the brain of patients. Superficially these inclusions are similar to those formed by polyglutamine (polyQ)-expanded Huntingtin exon 1 (Httex1) in Huntington's disease. Both have been reported to form an amyloid-like structure suggesting they might aggregate via similar mechanisms and therefore recruit the same repertoire of endogenous proteins.

Arginine in Dipolypeptides Mediates Promiscuous Proteome Binding and Multiple Modes of Toxicity.

-associated Motor Neuron Disease patients feature abnormal expression of 5 dipeptide repeat (DPR) polymers. Here we used quantitative proteomics in a mouse neuronal-like cell line (Neuro2a) to demonstrate that the Arg residues in the most toxic DPRS, PR and GR, leads to a promiscuous binding to the proteome compared with a relative sparse binding of the more inert AP and GA. Notable targets included ribosomal proteins, translation initiation factors and translation elongation factors.

A biosensor-based framework to measure latent proteostasis capacity.

The pool of quality control proteins (QC) that maintains protein-folding homeostasis (proteostasis) is dynamic but can become depleted in human disease. A challenge has been in quantitatively defining the depth of the QC pool. With a new biosensor, flow cytometry-based methods and mathematical modeling we measure the QC capacity to act as holdases and suppress biosensor aggregation.

A thiol probe for measuring unfolded protein load and proteostasis in cells.

When proteostasis becomes unbalanced, unfolded proteins can accumulate and aggregate. Here we report that the dye, tetraphenylethene maleimide (TPE-MI) can be used to measure cellular unfolded protein load. TPE-MI fluorescence is activated upon labelling free cysteine thiols, normally buried in the core of globular proteins that are exposed upon unfolding.

When proteostasis goes bad: Protein aggregation in the cell.

Protein aggregation is a hallmark of the major neurodegenerative diseases including Alzheimer's, Parkinson's, Huntington's and motor neuron and is a symptom of a breakdown in the management of proteome foldedness. Indeed, it is remarkable that under normal conditions cells can keep their proteome in a highly crowded and confined space without uncontrollable aggregation. Proteins pose a particular challenge relative to other classes of biomolecules because upon synthesis they must typically follow a complex folding pathway to reach their functional conformation (native state).

Manzamines: a potential for novel cures.

Manzamines are a unique class of β-carboline marine alkaloids with an unusual tetra- or pentacyclic system. These alkaloids have shown a variety of bioactivities against infectious diseases, cancer and inflammatory diseases. The greatest potential for the manzamine alkaloids appears to be against malaria, with improved potency relative to chloroquine and artemisinin.

Isolation, phylogenetic analysis and anti-infective activity screening of marine sponge-associated actinomycetes.

Terrestrial actinomycetes are noteworthy producers of a multitude of antibiotics, however the marine representatives are much less studied in this regard. In this study, 90 actinomycetes were isolated from 11 different species of marine sponges that had been collected from offshore Ras Mohamed (Egypt) and from Rovinj (Croatia). Phylogenetic characterization of the isolates based on 16S rRNA gene sequencing supported their assignment to 18 different actinomycete genera representing seven different suborders.

Bacterial community analyses of two Red Sea sponges.

Red Sea sponges offer potential as sources of novel drugs and bioactive compounds. Sponges harbor diverse and abundant prokaryotic communities. The diversity of Egyptian sponge-associated bacterial communities has not yet been explored.