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Vital diagnostics and devices in primary proper care diabetes.
Epidemiological studies have found that more physically active older participants have a reduced risk of Alzheimer disease. Based on enriched environment animal models, this effect is considered to result from physical exercise-induced molecular brain changes. This hypothesis has been tested in humans with randomized controlled trials involving physical exercise vs. more sedentary interventions with neuropsychological outcome measures. Fifty-one such randomized controlled trials were identified from Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines with keywords related to physical activity, cognition, and aging supplemented with reference list search. The five most popular executive function measures (each used in ≥8 trials) were meta-analyzed. Digit symbol was the only measure with a significant estimated overall effect size, indicating that physical exercise had a small (0.17) positive effect on change scores. Estimated overall effect sizes for physical exercise on Digit Span backward, Trails B, letter fluency, and Stroop Color-Word Interference time with/without correction were all not significantly different from zero. These results provide weak support for the notion that physical exercise produces molecular brain changes that enhance executive function test scores in older, nonclinical, participants.Introduction Anaplastic lymphoma kinase (ALK), a receptor tyrosine kinase, has been discovered in several cancers, including anaplastic large-cell lymphoma, non-small cell lung cancer, and inflammatory myofibroblastic tumors. BI-2493 inhibitor The deregulation of ALK activities, such as translocation and point mutation, results in human carcinogenesis. The use of ALK inhibitors in clinical cancer treatment has been shown to be efficacious, and the issue of resistance to ALK inhibitors has been reported. Consequently, the development of a new generation of ALK inhibitors is necessary.Areas covered This paper provides a comprehensive review of the patent literature from 2014 to 2018 including small molecule ALK inhibitors and their use as anticancer agents. The approved and developing ALK inhibitors are described.Expert commentary The available three generations of ALK inhibitors have shown a good anticancer effect in ALK-positive non-small cell lung cancer. An urgent issue in this field is ALK resistance development. The development of new ALK inhibitors through structure modification of currently available ALK inhibitors is proceeding, such as the synthesis of macrocyclic compounds. This article arranges the ALK inhibitors that have published in the patent in recent years. It may help in the investigation of a new generation of ALK inhibitors, which can overcome the resistance issue and development of novel drug candidates in the future.Introduction Amyotrophic lateral sclerosis (ALS) is a progressive and incurable neurodegenerative disorder that targets upper and lower motor neurons and leads to fatal muscle paralysis. Mutations in the superoxide dismutase 1 (SOD1) gene are responsible for 15% of familial ALS cases, but several studies have indicated that SOD1 dysfunction may also play a pathogenic role in sporadic ALS. SOD1 induces numerous toxic effects through the pathological misfolding and aggregation of mutant SOD1 species, hence a reduction of the levels of toxic variants appears to be a promising therapeutic strategy for SOD1-related ALS. Several methods are used to modulate gene expression in vivo; these include RNA interference, antisense oligonucleotides (ASOs) and CRISPR/Cas9 technology.Areas covered This paper examines the current approaches for gene silencing and the progress made in silencing SOD1 in vivo. It progresses to shed light on the key results and pitfalls of these studies and highlights the future challenges and new perspectives for this exciting research field.Expert opinion Gene silencing strategies targeting SOD1 may represent effective approaches for familial and sporadic ALS-related neurodegeneration; however, the risk of off-target effects must be minimized, and effective and minimally invasive delivery strategies should be fine-tuned.Introduction Tenofovir alafenamide (TAF)-containing fixed-dose drug combinations (FDCs) are increasingly being used in managing pregnant women living with HIV. However, TAF is not currently recommended during pregnancy due to limited pharmacokinetic and safety data. TAF, a newer nucleotide phosphonamidate prodrug of tenofovir (TFV), achieves high levels of tenofovir-diphosphate in lymphoid cells and hepatocytes, and 90% lower systemic concentrations of TFV compared to tenofovir disoproxil fumarate (TDF), thereby maximizing TAF's antiviral efficacy, potency and clinical safety.Areas covered This review discusses the currently available information on the pharmacology of TAF in pregnant women living with HIV. Pharmacokinetic studies with TAF during pregnancy have yielded varying results compared to postpartum, but TAF exposures during pregnancy have been within the range of those typically observed in non-pregnant adults. The efficacy and safety of TAF in treatment-naïve pregnant women living with HIV is currently being evaluated in the VESTED study, a phase-III NIH randomized clinical trial.Expert opinion Initial pregnancy data suggest that TAF-based FDCs have high efficacy and low risk of adverse effects during pregnancy. TAF is likely to become part of first-line regimens for use in pregnant women living with HIV once additional pregnancy data from phase III trials are available.Introduction RNA-based cancer gene therapy shows potential in cancer treatment. However, the safe and efficient transfer of therapeutic RNA to target cells has always been a challenge. The ideal drug delivery system should be effective with low immunogenicity and toxicity. Besides, a high specificity of drug delivery is necessary to improve efficacy and avoid the side effects associated with tumor heterogeneity. As endogenous RNA vehicles, extracellular vesicles (EVs) have shown their advantages and potential as drug delivery systems in gene therapy.Areas covered We summarize the performance of EVs as a drug delivery system in RNA-based cancer gene therapy and discuss the advantages, limitations, and potentials of this translational medicine. In addition, we compare the characteristics and differences of current drug delivery systems and expound the principles of selecting a drug delivery system suitable for cancer gene therapy.Expert opinion EVs are highly biocompatible membrane structures with low cytotoxicity which provide a new choice for drug delivery in RNA-based cancer gene therapy.
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