Propionic and valproic acids have an impact on bacteria viability, proton flux and ATPase activity.

Short-chain fatty acids like propionic (PPA) and valproic acids (VP) can alter gut microbiota, which is suggested to play a role in development of autism spectrum disorders (ASD). In this study we investigated the role of various concentrations of PPA and VP in gut enteric gram-negative Escherichia coli K12 and gram-positive Enterococcus hirae ATCC 9790 bacteria growth properties, ATPase activity and proton flux. The specific growth rate (µ) was 0.24 h-1 and 0.82 h-1 in E. coli and E. hirae, respectively. Different concentrations of PPA reduced the value of µ similarly in both strains. PPA affects membrane permeability only in E. hirae. PPA decreased DCCD-sensitive ATPase activity in the presence of K+ ions by 20% in E. coli and 40% in E. hirae suggesting the importance of the FOF1-K+ transport system in the regulation of PPA-disrupted homeostasis. Moreover, the H+ flux during PPA consumption could be the protective mechanism for enteric bacteria. VP has a selective effect on the µ depending on bacteria. The overwhelming effect of VP was detected on the K+-promoted ATPase activity in E. hirae. Taken together it can be suggested that PPA and VP have a disruptive effect on E. coli and E. hirae growth, viability, bioenergetic and biochemical properties, which are connected with the alteration of FOF1-ATPase activity and H+ flux rate or direction.

The Involvement of Insulin-Like Growth Factor 1 and Nerve Growth Factor in Alzheimer's Disease-Like Pathology and Survival Role of the Mix of Embryonic Proteoglycans: Electrophysiological Fingerprint, Structural Changes and Regulatory Effects on Neurotrophins.

Alzheimer's disease (AD)-associated neurodegeneration is triggered by different fragments of amyloid beta (Aß). Among them, Aß (25-35) fragment plays a critical role in the development of neurodegeneration-it reduces synaptic integrity by disruption of excitatory/inhibitory ratio across networks and alters the growth factors synthesis. Thus, in this study, we aimed to identify the involvement of neurotrophic factors-the insulin-like growth factor 1 (IGF-1) and nerve growth factor (NGF)-of AD-like neurodegeneration induced by Aß (25-35). Taking into account our previous findings on the neuroprotective effects of the mix of proteoglycans of embryonic genesis (PEG), it was suggested to test its regulatory effect on IGF-1 and NGF levels. To evaluate the progress of neurodegeneration, in vivo electrophysiological investigation of synaptic activity disruption of the entorhinal cortex-hippocampus circuit at AD was performed and the potential recovery effects of PEG with relative structural changes were provided. To reveal the direct effects of PEG on brain functional activity, the electrophysiological pattern of the single cells from nucleus supraopticus, sensomotor cortex and hippocampus after acute injection of PEG was examined. Our results demonstrated that after i.c.v. injection of Aß (25-35), the level of NGF decreased in cerebral cortex and hypothalamus, and, in contrast, increased in hippocampus, prompting its multidirectional role in case of brain damage. The concentration of IGF-1 significantly increased in all investigated brain structures. The administration of PEG balanced the growth factor levels accompanied by substantial restoration of neural tissue architecture and synaptic activity. Acute injection of PEG activated the hypothalamic nucleus supraopticus and hippocampal neurons. IGF-1 and NGF levels were found to be elevated in animals receiving PEG in an absence of amyloid exposure. We suggest that IGF-1 and NGF play a critical role in the development of AD. At the same time, it becomes clear that the neuroprotective effects of PEG are likely mediated via the regulation of neurotrophins.

Advances in the Treatment of Autism Spectrum Disorder: Current and Promising Strategies.

Autism spectrum disorder (ASD) is an umbrella term for developmental disorders characterized by social and communication impairments, language difficulties, restricted interests, and repetitive behaviors. Current management approaches for ASD aim to resolve its clinical manifestations based on the type and severity of the disability. Although some medications like risperidone show potential in regulating ASD-associated symptoms, a comprehensive treatment strategy for ASD is yet to be discovered. To date, identifying appropriate therapeutic targets and treatment strategies remains challenging due to the complex pathogenesis associated with ASD. Therefore, a comprehensive approach must be tailored to target the numerous pathogenetic pathways of ASD. From currently viable and basic treatment strategies, this review explores the entire field of advancements in ASD management up to cutting-edge modern scientific research. A novel systematic and personalized treatment approach is suggested, combining the available medications and targeting each symptom accordingly. Herein, summarize and categorize the most appropriate ways of modern ASD management into three distinct categories: current, promising, and prospective strategies.