Fighting against amyotrophic lateral sclerosis (ALS) with flavonoids: a computational approach to inhibit superoxide dismutase (SOD1) mutant aggregation.

Protein aggregation is a biological process that occurs when proteins misfold. Misfolding and aggregation of human superoxide dismutase (hSOD1) cause a neurodegenerative disease called amyotrophic lateral sclerosis (ALS). Among the mutations occurring, targeting the E21K mutation could be a good choice to understand the pathological mechanism of SOD1 in ALS, whereof it significantly reduces life hopefulness in patients. Naturally occurring polyphenolic flavonoids have been suggested as a way to alleviate the amyloidogenic behavior of proteins. In this study, computational tools were used to identify promising flavonoid compounds that effectively inhibit the pathogenic behavior of the E21K mutant. Initial screening identified Pelargonidin, Curcumin, and Silybin as promising leads. Molecular dynamics (MD) simulations showed that the binding of flavonoids to the mutated SOD1 caused changes in the protein stability, hydrophobicity, flexibility, and restoration of lost hydrogen bonds. Secondary structure analysis indicated that the protein destabilization and the increased propensity of ß-sheet caused by the mutation were restored to the wild-type state upon binding of flavonoids. Free energy landscape (FEL) analysis was also used to differentiate aggregation, and results showed that Silybin followed by Pelargonidin had the most therapeutic efficacy against the E21K mutant SOD1. Therefore, these flavonoids hold great potential as highly effective inhibitors in mitigating ALS's fatal and insuperable effects.Communicated by Ramaswamy H. Sarma.

Quercetin and Its Role in Reducing the Expression of Pro-inflammatory Cytokines in Osteoarthritis.

Osteoarthritis is the most common human joint disease in the world. It is also one of the most common skeletal muscle defects, destructive joint changes, and the leading cause of disability and reduced quality of life. Destructive changes in inflammatory joints are associated with a range of biochemical events, including the overproduction of inflammatory cytokines. Cytokines are protein compounds that play an essential role in causing and regulating inflammation. A balance between pro-inflammatory and anti-inflammatory cytokines is crucial in maintaining a stable body. In some inflammatory diseases, including osteoarthritis, the balance between these compounds is disturbed, and the balance shifts to pre-inflammatory cytokines. For this reason, researchers today are trying to find an effective way to reduce inflammation and treat osteoarthritis by using certain compounds. Current treatments for osteoarthritis, including nonsteroidal antiinflammatory drugs, glucocorticoids, and hyaluronic acid, are mainly based on reducing pain and inflammation. However, they have limited effects in controlling symptoms and improving the patient's quality of life. Also, due to the high level of side effects, synthetic drugs have led to the identification of compounds of natural origin to give patients a chance to use painkillers and antiinflammatory drugs with fewer side effects. This review study aimed to present the role of quercetin as a natural compound in reducing the expression of pro-inflammatory cytokines in osteoarthritis. This study also discusses the relationship between inflammation and cartilage destruction and other inflammation-related factors caused by cytokines.

[COMPARISON OF CLINICAL AND DEMOGRAPHIC CHARACTERISTICS OF ARAB AND JEWISH CHILDREN LIVING IN THE GALILEE WHO HAVE SUFFERED FROM AN INTESTINAL INFECTION CAUSED BY CAMPYLOBACTER].

INTRODUCTION: Among all infectious agents that cause gastrointestinal infection in children, the most common is the Campylobacter bacterium. The bacterium has multiple virulence factors such as motility, adhesion and invasion of the human intestinal lining, and enzyme secretion. In recent years, there has been a worldwide increase in Campylobacter resistance to antibiotics. AIMS: To examine the frequency of Campylobacter among children who were hospitalized at the Poriya Medical Center during 2012-2014 and suffered from an intestinal infection caused by Campylobacter; to compare the demographic, clinical, and laboratory data of Jewish and Arab children; to examine the resistance rate of the bacterium to antibiotics. METHODS: The data on Campylobacter frequency in children who suffered from an intestinal infection was extracted from the medical records: age, sex, hospitalization duration, hemoglobin and leukocyte values in blood chemistry, the residential environment, and antibiotic treatment during hospitalization. In addition, antibiotic susceptibility tests were performed for Erythromycin and Ciprofloxacin for all Campylobacter cultures that were isolated from patients' stool samples and kept frozen. RESULTS: Campylobacter is the most prevalent bacterial factor among children who were hospitalized following enteritis. There are differences in the bacterium frequency among Jewish children in comparison to frequency in Arab children in the following aspects: Campylobacter is more frequent in Arab children, more common among children living in rural areas, and especially those of Arab origin. Arab children were hospitalized for longer durations than Jewish children. The mean age of Jewish children who suffered from infection caused by Campylobacter was higher compared to the mean age of Arab children. No difference was found in leukocyte values in the cell count. Hemoglobin values were lower among Jewish children compared to Arab children. There was a high percentage of children treated with antibiotics due to intestinal infection caused by Campylobacter, especially among Arab children. Resistance to Erythromycin was not found; however the rate of resistance to Ciprofloxacin was 10.7%. CONCLUSIONS: There are significant differences in intestinal infection caused by Campylobacter among Jewish and Arab children in parameters such as: mean age, hospitalization duration, and residential area. The antibiotic resistance rate that was found is low; however, presently, it still exists.