Howard Berg had proposed a ‘rotary motor’ explanatory paradigm for the flagella-assisted motility of bacteria (1), claiming that proton motive force (pmf) provided the powering in such propulsion in low Reynold’s number regimes (2). Paul Boyer subsequently suggested a pmf-aided rotary functionalism for explaining Complex V’s role in photo-/oxidative- phosphorylations in chloroplasts/mitochondria. Michael Behe had questioned the ‘evolvability’ of such self-assembled multi-molecular protein complexes with rotary functions, calling these proposals ‘irreducibly complex’. Over the last 25 years, while championing a new stochastic cellular principle of life (complementing the deterministic principle of central dogma) called murburn concept, we discredited the idea of “pmf-assisted rotary functions” in cellular routines in the two systems above. Herein, we confirm some of our earlier predictions and provide further evidence/arguments supporting the murburn model of flagella-aided motility in bacteria: (i) the component proteins of C-ring and Mot proteins show large variations in monomeric constitution and amino acid sequences suggesting that they could not have evolved for rotary activity (3), the purported rotary fulcrum role of a single amino acid residue (MotB’s D/E32) is untenable as it is not conserved in a wide variety of bacteria surveyed, (iii) the C-ring proteins and cytoplasm-side of MotA have a relatively higher concentration of charged residues that enable DRS recruitment/utilization, and (iv) the basal module is a Type-3 secretory system ejecting fluid wherein MotAB complex enable efficient proton delivery for water formation and expulsion via the rod.
Apelin is an endogenous ligand for apelin receptor (APLNR), a G protein-coupled receptor (GPCR). This peptide is derived from a 77aa long pre-proapelin. Upon cleavage by different peptidases, several isoforms that bind to the receptor with different strength and downstream effects are created. Many cellular processes that are regulated by the apelinergic system have been discovered – neural and immune functions, blood pressure regulation, fluid homeostasis, hormonal release, cellular proliferation, etc. Additional research has been also made to elucidate the role of the system in pathological conditions affecting the brain and the peripheral organs. In this review, we summarise the distribution of the apelinergic system components in the mammalian organism. We also include a comparative analysis between three different species - human (Homo sapiens), mouse (Mus mus-culus), and rat (Rattus norvegicus).
Subependymal giant cell astrocytomas (SEGA) are WHO CNS grade 1 tumors, predominantly diagnosed in the pediatric and young adult populations and almost always encountered in the context of the tuberous sclerosis complex (TSC). SEGAs develop from subependymal nodular (SEN), which are a component of TSC, while both have similar radiological and histological. Char-acteristically, SEN are small lesions that are growth stable and typically do not produce symptoms, while SEGAs are steadily growing lesions that produce compression-associated symptoms due to their periventricular location. Histologically, SEGAs present with pleomorphic, epitheloid-like, and giant multinucleated cells, with other glial phenotypes such as pyloid, histiocytic, and others also present. Tumors are sharply demarcated from the surrounding parenchyma and, other than the striking cellular appearance, may also show areas of palisading necrosis, making the histopathological diagnosis challenging. In cases of older patients or when a history of TSC is either not present or not known by the neuropathologist, the differential diagnosis can be quite challenging and includes a myriad of either lower-grade neuroglial tumors as well as high-grade astrocytic ones. Herein, we present a neuropathological case report of a 63-year-old female with no known TSC history and a CNS tumor with morpho-logical characteristics of SEGA.
The direct healthcare side effects of the coronavirus disease identified in 2019 (COVID-19) caused by the severe acute respira-tory syndrome coronavirus 2 (SARS-CoV-2) are immeasurable. Furthermore, the chronic sequels of the disease are yet to be adequately studied and evaluated in the context of the post-infectious specter, referred to as a post-COVID syndrome. One of the most commonly reported such sequel is the so-called "brain fog" – loss of concentration, learning difficulties, and confu-sion. Herein, we analyzed a series of 50 autopsies of RT-PCR-proven COVID-19. Central nervous system (CNS) samples were obtained in 49 of the cases, with dentate gyrus samples acquired in 9 of them. Histopathological spectrums of hippocampal changes included vascular, degenerative, apoptotic, and necrotic on H&E stains with varying severity. The diffuse nature of the vascular changes, together with the epitheliotropic and especially the endotheliotropic nature of SARS-CoV-2, would suggest that the CNS damage is both hypoxic and vasculotropic. Infected endothelial cells bulge and desquamate (necrosis), disrupting the blood-brain barrier and secondary damage to the neurons by permeating plasma substances.
Objective: This narrative review aims to provide a comprehensive analysis of global studies on the prevalence and patterns of malnutrition in individuals with cerebral palsy (CP). By examining the available evidence, this review seeks to enhance our understanding of malnutrition in CP, identify research gaps, and propose directions for future research. Methods: A systematic search was conducted in PubMed, Scopus, Mendeley and Web of Science databases to identify relevant studies published between 2018 and February 2023. Studies reporting original observations in children and adolescents with CP, and measuring malnutrition through anthropometric measures, biochemical tests, or other nutritional factors, were included. The Systematic Review and Narrative Appraisal (SANRA) guidelines were followed during the review process. Results: A total of 28 studies met the inclusion criteria and were included in the review. The studies were conducted in more than 25 countries across all continents, providing a global perspective on malnutrition in CP. The prevalence of malnutrition varied across regions, with rates ranging from 15.4% to 92.6% for underweight, and 35% to 85.9% for stunting. Several factors, including motor impairment severity, feeding difficulties, and sociodemographic factors, were associated with malnutrition in CP. Micronutrient deficiencies, such as iron deficiency anemia, were also observed in some studies. Conclusion: This comprehensive narrative review highlights the significant prevalence of malnutrition in individuals with CP globally. The findings underscore the need for comprehensive nutritional assessments, tailored interventions, and close monitoring of nutritional status in clinical practice. By addressing malnutrition, healthcare professionals can improve the overall health, growth, and quality of life for individuals with CP. Further research is needed to explore the long-term trajectories of malnutrition in CP and to develop evidence-based interventions to mitigate its impact on this vulnerable population.
Background: The initial 1000 days of human life, from conception to two years of age, are crucial for health growth and neuropsychological development. This period's primary environmental influence is maternal nutrition, which significantly impacts the development of the fetal nervous system. Objectives: This review aims to synthesize current literature on the effects of dietary patterns and nutritional status of pregnant women on the neurodevelopment of their offspring. Methods: Adhering to the Scale for the Quality Assessment of Narrative Review Articles (SANRA) and elements of the PRISMA guidelines, we conducted a systematic literature search in electronic databases including PubMed, Scopus, and Mendeley, focusing on publications from 2018 to 2023. Results: Our review encapsulates findings from 25 peer-reviewed articles, highlighting the influence of various nutrients like polyunsaturated fatty acids (PUFAs), vitamin D, folate, iodine, and iron on child neurodevelopment. Studies also examined the effects of maternal dietary patterns, body mass index (BMI), and alcohol exposure. Key findings indicate the crucial role of balanced maternal nutrition in optimal neurodevelopmental outcomes in children. Discussion: The review reveals intricate relationships between maternal dietary habits, supplementation, and child growth and neurological development. While some nutrients show clear benefits, others present mixed findings, underlining the complexity of maternal nutrition's role in child development. Conclusion: The review underscores the importance of balanced maternal nutrition for favorable neurodevelopmental outcomes in offspring, calling for more detailed research to understand the nuanced roles of specific nutrients and dietary patterns.
The cytoskeleton is a sophisticated cellular system consisted of actin filaments, intermediate filaments and microtubules (MT) accompanied by a large number of associated structural and motor proteins. Microtubules are dynamically assembling and disassembling structures. They are pivotal for many cell functions, e.g. intracellular traffic of membrane-bound organelles in endocytosis and protein secretion, also a variety of inflammatory and signal transduction pathways. Tubulin is the major building protein of MT. Depended on doses, agents that bind to tubulin inhibit its assembly, that is, MT formation, or disas-semble the preformed MT. Such tubulin-binding agents are named MT-disassembling agents or antitululins, colchicine being a classical member of these agents. Herein, we describe in brief the scientific saga of colchicine as related to the therapy of car-diovascular diseases such as acute coronary syndromes, myocardial infarction, atrial fibrillation, pericarditis, and hypertrophic cardiomyopathy.
Alkyl/aryl dithiocarbonic acid derivatives (xanthates) are chemical compounds with various biological effects on the base of inhibition of important enzyme systems and antioxidant action. In this review we describe our results in comparing antiprolif-erative activity and cytotoxicity to different tumor cells with the structure of different xanthates. To elucidate the mechanism of this activity it is compared with the effect on normal cells, the time of manifestation of the effect, the influence on the cytotoxic activity in combination with lauric acid and epirubicine. The main conclusions from these experiments could be summarized like that: the selectivity and magnitude of cytotoxic tumor cells effect of xanthates is based on the differences in expression of PC-specific phospholipase C (PC-PLC) activity; PLC inhibition suppress Nuclear Factor-κB activation and inhibited ceramide translocation from endoplasmic reticulum pool to Golgi complex; differences in tumor cells xanthates sensitivity could be due to different ROS production as the xanthates are well known antioxidants.
The enteric nervous system exerts local control on the gastrointestinal motility, exocrine and endocrine secretions, ensures proper blood supply, and modulates the immune and inflammatory processes in the gut. The aim of this paper is to give insights into current advances and present knowledge about morphology of the myenteric plexus and the neurochemical coding of adult rat myenteric neurons in the large intestine with a special emphasis on non-adrenergic, non-cholinergic (NANC) transmitters. Major neuroactive substances involved in the NANC transmission include nitric oxide (NO), tachykinins, mostly substance P (SP), and adenosine triphosphate (ATP), co-localized in variable proportions with other neuroactive substances. After applying NADPH-diaphorase enzyme histochemistry and neuronal NO synthase (nNOS) immunohistochemistry, we were able to dem-onstrate numerous nitrergic somata of myenteric neurons with Dogiel type I morphology. In addition to the observed nitrergic distributional patterns, significant variations were registered in the staining intensity of myenteric structures in the colon and anorectal area. Immunohistochemistry for SP revealed an abundance of intensely stained SP-immunoreactive varicose fibers, ensheathing the immunonegative myenteric neuronal cell bodies in a basket-like manner. ATPergic structures were mostly limited to fiber bundles surrounding unstained myenteric neurons and penetrating the two muscle layers. An important finding was the notable presence of purinergic immunoreactive nerve fiber bundles in the longitudinal muscle layer. In conclusion, our results show that the cytoarchitecture and morphometric properties appeared to mimic their equivalent in the more proximal parts of the rat digestive tract and in other experimental animals.
This narrative review provides a significant contribution to the field of developmental disabilities by providing a comprehensive and up-to-date analysis of the prevalence and patterns of malnutrition in individuals with cerebral palsy. The findings from this study shed light on the high prevalence of malnutrition and associated factors, such as motor impairment severity, functional limitations, feeding difficulties, and socio-demographic factors. By synthesizing the existing literature from global studies, this manuscript enhances our understanding of the complex relationship between malnutrition and cerebral palsy, providing valuable insights for clinicians, researchers, and policymakers. The comprehensive nature of this review, encompassing various continents and countries, helps to identify regional variations in malnutrition prevalence and highlights the need for targeted interventions and tailored nutritional care strategies for individuals with cerebral palsy worldwide.
