mTOR signaling and Alzheimer's disease: What we know and where we are?

Despite the great body of research done on Alzheimer's disease, the underlying mechanisms have not been vividly investigated. To date, the accumulation of amyloid-beta plaques and tau tangles constitutes the hallmark of the disease; however, dysregulation of the mammalian target of rapamycin (mTOR) seems to be significantly involved in the pathogenesis of the disease as well. mTOR, as a serine-threonine protein kinase, was previously known for controlling many cellular functions such as cell size, autophagy, and metabolism. In this regard, mammalian target of rapamycin complex 1 (mTORC1) may leave anti-aging impacts by robustly inhibiting autophagy, a mechanism that inhibits the accumulation of damaged protein aggregate and dysfunctional organelles. Formation and aggregation of neurofibrillary tangles and amyloid-beta plaques seem to be significantly regulated by mTOR signaling. Understanding the underlying mechanisms and connection between mTOR signaling and AD may suggest conducting clinical trials assessing the efficacy of rapamycin, as an mTOR inhibitor drug, in managing AD or may help develop other medications. In this literature review, we aim to elaborate mTOR signaling network mainly in the brain, point to gaps of knowledge, and define how and in which ways mTOR signaling can be connected with AD pathogenesis and symptoms.

Relation between ADHD and COVID-19: A Narrative Review to Guide Advancing Clinical Research and Therapy.

Objective: To cope with the COVID-19 pandemic, national health authorities temporarily closed cultural, religious, and educational institutions such as universities and schools. Children and adolescents with ADHD were challenged with the restrictions caused by the Covid-19 pandemic such as homeschooling and reduced physical activity. The present narrative review aimed to summarize the state-of-the-art regarding associations between COVID-19-related social restrictions and possible psychological and behavioral issues in children and adolescents with ADHD. Additionally, we discussed the underlying possible reasons of the association focusing on the role of parental influence and physical activity, vulnerabilities of individuals with ADHD to Covid-19 infection and to school closure and remote learning. Method: To collect data for the present narrative review, recent publications on these topics between February 1st, 2020 and January 10th, 2021 were retrieved from the most popular search engines (PubMed; Scopus; Google Scholar; Psych Info; Embase) through a comprehensive search using relevant keywords. Results: During confinement, children and adolescents with ADHD reported increased behavioral and ADHD-related symptoms and overall decreased psychological well-being. Factors negatively impacting children's and adolescents' behavioral symptoms and well-being were: less physical activity, adverse parental behavior, difficulties in coping with preventive guidelines, and school closure and remote learning consequences. Conclusion: Children and adolescents with ADHD and their caregivers faced both specific and general psychological issues related to the school lockdowns and homeschooling. Additionally, Individuals with ADHD seem to be more vulnerable to Covid-19 infection which highlights the need for better healthcare adaptation.

Combined therapy of photobiomodulation and adipose-derived stem cells synergistically improve healing in an ischemic, infected and delayed healing wound model in rats with type 1 diabetes mellitus.

OBJECTIVE: We assessed the therapeutic effects of photobiomodulation (PBM) and adipose-derived stem cell (ADS) treatments individually and together on the maturation step of repairing of a delayed healing wound model in rats with type 1 diabetes mellitus (DM1). RESEARCH DESIGN AND METHODS: We randomly assigned 24 rats with DM1 to four groups (n=6 per group). Group 1 was the control (placebo) group. In group 2, allograft human ADSs were transplanted. Group 3 was subjected to PBM (wavelength: 890 nm, peak power output: 80 W, pulse frequency: 80 Hz, pulsed duration: 180 ns, duration of exposure for each point: 200 s, power density: 0.001 W/cm2, energy density: 0.2 J/cm2) immediately after surgery, which continued for 6 days per week for 16 days. Group 4 received both the human ADS and PBM. In addition, we inflicted an ischemic, delayed healing, and infected wound simulation in all of the rats. The wounds were infected with methicillin-resistant Staphylococcus aureus (MRSA). RESULTS: All three treatment regimens significantly decreased the amount of microbial flora, significantly increased wound strength and significantly modulated inflammatory response and significantly increased angiogenesis on day 16. Microbiological analysis showed that PBM+ADS was significantly better than PBM and ADS alone. In terms of wound closure rate and angiogenesis, PBM+ADS was significantly better than the PBM, ADS and control groups. CONCLUSIONS: Combination therapy of PBM+ADS is more effective that either PBM or ADS in stimulating skin injury repair, and modulating inflammatory response in an MRSA-infected wound model of rats with DM1.