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CHIP and aging: a key regulator of proteostasis and cellular senescence

Degradation of proteostasis, mitochondrial function, and cellular stress resistance results in a build-up of damaged proteins, oxidative insult, and chronic inflammation, characteristic of aging. CHIP is essential for maintaining protein quality control and cellular homeostasis by having dual E3 ubiquitin ligase and co-chaperone activities. CHIP facilitates proteostasis by maintaining proteostasis in misfolded, aggregated proteins by promoting their degradation. Mitochondrial dysfunction, oxidative imbalance, and cellular senescence are caused by its age-associated decline and contribute to neurodegenerative, cardiovascular, and oncogenic disease pathogenesis. Examples of recent pharmacological and gene-based strategies to correct CHIP and restore stress resilience have been made.

Running injuries often strike suddenly, not gradually: Study challenges understanding of overuse injuries

A new study from Aarhus University turns our understanding of how running injuries occur upside down. The research project, which is the largest of its kind ever conducted, shows that running-related overuse injuries do not develop gradually over time, as previously assumed, but rather suddenly—often during a single training session. The research is published in the British Journal of Sports Medicine.

“Our study marks a paradigm shift in understanding the causes of running-related overuse injuries. We previously believed that injuries develop gradually over time, but it turns out that many injuries occur because runners make training errors in a single training session,” explains Associate Professor Rasmus Ø. Nielsen from the Department of Public Health at Aarhus University, who is the lead author of the study.

The study followed 5,205 runners from 87 countries over 18 months and shows that injury risk increases exponentially when runners increase their distance in a single training session compared to their longest run in the past 30 days. The longer the run becomes, the higher the injury risk.

Protein aggregation is linked to altered RNA processing

Neurodegenerative disorders, such as Alzheimer’s disease and Parkinson’s disease, are devastating and incurable diseases. Although many neurodegenerative diseases are characterized by abnormal protein aggregation in the brain, a limited understanding of whether and how aggregated proteins cause brain cell dysfunction and death represents a major barrier to developing effective treatments.

Inspired by similar approaches in cardiovascular disease and cancer, the researchers focused on rare genetic forms of neurodegeneration as a powerful way to uncover fundamental mechanisms tying protein aggregation to brain disease. Thier work unexpectedly linked protein aggregation in genetic forms of neurodegeneration to disrupted processing of transfer RNAs (tRNAs), revealing an important mechanism that might be therapeutically targeted in these disorders.

The authors were interested in genetic forms of neurodegeneration caused by GGC trinucleotide repeat expansions (DNA sequence mutations caused by copying this 3-letter sequence too many times in a row). These mutations produce aggregation-prone proteins with long stretches of a single repeated amino acid (glycine).

Reversing The Age-Related DHEA-S Decline: Cholesterol, Gut Bacteria

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Characterization of the antibacterial activity of Bald’s eyesalve against drug resistant Staphylococcus aureus and Pseudomonas aeruginosa

In this study, we have shown that Bald’s eyesalve, an Anglo-Saxon remedy for eye sty infections, displays growth inhibitory activity against S. aureus and P. aeruginosa, including a multi-drug resistant strain. This activity was more pronounced against S. aureus than P. aeruginosa, which is consistent with the fact that Gram-negative bacteria, particularly Pseudomonads, are notably more resistant to antibacterial agents than Gram-positive bacteria, including Staphylococcus sp. [12]. Our data indicate that the specific formulation composition had little impact on the inhibition of S. aureus. This is inconsistent with a previous report where the presence of an additional Allium species, onion or leek, was found to significantly contribute to the antibacterial activity of Bald’s eyesalve [6]; however, this previous study evaluated the antibacterial activity using a synthetic wound model in which S. aureus inoculum was grown as a biofilm for 24 hr prior to treatment and based upon colony-forming units [6]. Our conflicting results may be due to our assessment of the antibacterial activity of Bald’s eyesalve exclusively against planktonic S. aureus rather than S. aureus biofilms, and we did not investigate whether onion or leek are necessary for specific efficacy against bacterial biofilms. Previous studies have shown that quercetin, an antibacterial flavonoid found in onion [13], and its derivatives demonstrate anti-biofilm and anti-quorum sensing activity against S. aureus and P. aeruginosa [14, 15]. Although plant extracts have been shown to display growth inhibitory activity against P. aeruginosa [16, 17], to our knowledge our study represents the first report of the antibacterial efficacy of Bald’s eyesalve against P. aeruginosa.

Although all known Allium species contain organosulfur compounds, the chemical composition and resultant antibacterial activity of their extracts greatly varies [18]. Prior investigations have determined the main constituents of garlic essential oil to be diallyl disulfide (DADS), diallyl trisulfide (DATS), allyl methyl trisulfide, diallyl sulfide (DAS), and diallyl tetrasulfide (DATTS), while the main constituents of onion and leek essential oils were found to be dipropyl disulfide, dipropyl trisulfide, methyl propyl disulfide, methyl propyl trisulfide, and 1-propenyl propyl disulfide [18, 19]. Tsao et al. previously demonstrated that DAS, DADS, DATS, and DATTS exhibit MICs of 20, 4, 2, and 0.5 μg/ml against S. aureus, respectively, and 80, 64, 32, and 12 μg/ml against P. aeruginosa, respectively [20, 21].

Inhaled farm dust alters gut bacteria and weakens intestinal barrier in mice

Inhaling agricultural dust may pose significant risks to gut health for workers in animal agriculture, a University of California, Riverside, study has found.

Led by Declan McCole, a professor of biomedical sciences in the UCR School of Medicine, the study expands on prior findings that hog farm causes airway inflammation. The researchers now report in the Journal of Applied Toxicology that inhaling this dust also alters the gut microbiome and impairs intestinal function, including increased “” or intestinal permeability. Leaky gut is associated with a range of chronic diseases, including , celiac disease, and type 1 diabetes.

“Exposure to swine farm dust, which contains high levels of bacteria and endotoxins, caused both airway inflammation and increased passage of gut bacterial products into the bloodstream in our mouse models,” said Meli’sa Crawford, a former postdoctoral researcher in McCole’s lab and the paper’s first author. “But what’s especially striking is the impact we observed on the and metabolism.”