Pathological Targets for Treating Temporal Lobe Epilepsy: Discoveries From Microscale to Macroscale

Temporal lobe epilepsy (TLE) is one of the most common and severe types of epilepsy, characterized by intractable, recurrent, and pharmacoresistant seizures. Histopathology of TLE is mostly investigated through observing hippocampal sclerosis (HS) in adults, which provides a robust means to analyze the related histopathological lesions. However, most pathological processes underlying the formation of these lesions remain elusive, as they are difficult to detect and observe. In recent years, significant efforts have been put in elucidating the pathophysiological pathways contributing to TLE epileptogenesis. In this review, we aimed to address the new and unrecognized neuropathological discoveries within the last 5 years, focusing on gene expression (miRNA and DNA methylation), neuronal peptides (neuropeptide Y), cellular metabolism (mitochondria and ion transport), cellular structure (microtubule and extracellular matrix), and tissue-level abnormalities (enlarged amygdala). Herein, we describe a range of biochemical mechanisms and their implication for epileptogenesis. Furthermore, we discuss their potential role as a target for TLE prevention and treatment. This review article summarizes the latest neuropathological discoveries at the molecular, cellular, and tissue levels involving both animal and patient studies, aiming to explore epileptogenesis and highlight new potential targets in the diagnosis and treatment of TLE.

Terpenoids of plants in arid environments.

Arid and desert environments are characterized by the sparse and discontinuous vegetation cover. Species that have been able to survive difficult bioclimatic conditions and adapt from generation to generation in these areas had to develop physiological and biochemical mechanisms of tolerance and/or resistance. The use of secondary metabolites, specifically terpenoids, is predominant in most of the biotic and abiotic interactions in which these plants are involved. Studies have shown their roles in the prevention of oxidative stress by intervening in thermo-tolerance, water stress, and salt stress generalized in a model of "the protective role of volatile compounds" explained by a single biochemical mechanism. Other studies have proven the functions of terpenoids in direct and indirect defenses against natural enemies, herbivores, and pathogenic microorganisms, in the attraction of pollinators, in competition and facilitation and other interactions between plants. This review mainly summarizes the recent research progress on the adaptation mechanisms of plants in arid environments and the biological and ecological roles of terpenoids in the various biotic and abiotic interactions.

Plant hormones accumulation and its relationship with symplastic peroxidases expression during carnation-Fusarium oxysporum interaction

The vascular wilting caused by Fusarium oxysporum f. sp. dianthi (Fod) is the most relevant disease for carnation cultivation. Understanding the biochemical mechanisms involved in resistance to Fod will allow the development of new disease control strategies. In this research, the levels of some phytohormones such as salicylic acid (SA), methyl salicylate (MeSA), and methyl jasmonate (MeJA) were evaluated in symplast of carnation roots infected with this pathogen. The accumulation of these hormones was then correlated with the expression levels of symplastic peroxidases, enzymes involved in the plant resistance against pathogen during interaction. Our results suggested that pathogen infection causes a differential accumulation of SA, MeSA, and MeJA in a resistant cultivar (i.e. ‘Golem’), being earlier and higher than that observed in a susceptible one (i.e. ‘Solex’). Simultaneously, an increase of guaiacol peroxidase enzymatic activity (GPX) and transcriptional levels of a gene coding for a symplastic peroxidase were presented as part of the resistance response. The positive statistical correlation between the accumulation of SA and MeJA and the expression of peroxidases (GPX activity and mRNA levels) indicates the possible cellular relationship of these phenomena during the activation of the resistance to Fod. Our findings suggested some hormonal signaling mechanisms acting at the roots during the regulation of the biochemical response associated with resistance against Fod.

Effect of lipopolysaccharide (LPS) on HAEC cells. Does nicotinamide N-methyltranferase sensitize HAEC cells to LPS?

Treatment of endothelial cells with bacterial lipopolysaccharide (LPS) evokes a number of metabolic and functional consequences which built a multifaceted physiological response of endothelium to bacterial infection. Here effects of LPS on human aortic endothelial cells (HAEC) have been investigated. Among the spectrum of biochemical changes substantially elevated N-nicotinamide methyltransferase (NNMT) protein level was particularly intriguing. It has been shown that silencing of the NNMT-encoding gene prevented several changes which are observed in control HAECs due to treatment with LPS. They include significantly increased cytosolic Ca2+ concentration and abnormally strong calcium response to thapsigargin, altered energy metabolism which is switched to anaerobic glycolysis and rearrangement of the mitochondrial network organization. Biochemical mechanisms behind protecting effect of partial NNMT deficiency remains unknown but we speculate that the primary role in this phenomenon is attributed to normalized Ca2+ response in cells partially deprived of the NNMT gene. However, this assumption needs to be verified experimentally. Nevertheless, this paper focuses the reader attention on NNMT, which is an important enzyme that potentially may affect cellular metabolism by two means: direct influence based on a regulation of NAD+ synthesis through modulation of nicotinamide availability, and a regulation of S-adenosylmethionine concentration and therefore controlling of methylation processes including modification of chromatin and epigenetic effects

Animal Placental Therapy: An emerging tool for Health Care.

Background: The placenta maintains and regulates the growth of foetus and consists of various biologically active nutrients such as cytomedines, vitamins, trace elements, amino acids, peptides, growth factors and other biologically active constituents. Introduction: The therapeutic effectiveness of the placenta can be well defined with respect to several biochemical mechanisms of various components present in it. The placental extract derived from biomedical wastes has also shown a great potential for treatment of various diseases. Method: Placental therapy has been reported specifically to have potent action on treatment of diseases and tissue regeneration. Result: Placental bioactive components and their multi-targeting identity prompted us to compile the précised information on placental extract products. However, some findings are needed to be explored by scientific community to prove their clinical potential with significant statistical validation. Conclusion: In the light of available information and the usefulness of the placental extract, it is necessary that the formulations of various desirable properties may be developed to meet the clinical requirements in several treatment paradigms. It is also a matter of exploration that the short- and long-term adverse effects to be explored by advanced scientific techniques.

Evolution of Enterococcus faecium to A Combination of Daptomycin and Fosfomycin Reveals Distinct and Diverse Adaptive Strategies

Infections caused by vancomycin-resistant Enterococcus faecium (VREfm) are an important public health threat. VREfm have become increasingly resistant to the front-line antibiotic, daptomycin (DAP). As such, the use of DAP combination therapies (like fosfomycin [FOS]), has received increased attention. Antibiotic combinations could extend the efficacy of current available antibiotics and potentially delay the onset of further resistance. We investigated the potential for E. faecium HOU503, a clinical VREfm isolate that is DAP and FOS susceptible, to develop resistance to a DAP-FOS combination. Of particular interest was whether the genetic drivers for DAP-FOS resistance might be epistatic and, thus, potentially decrease the efficacy of a combinatorial approach in either inhibiting VREfm or in delaying the onset of resistance. We show that resistance to DAP-FOS could be achieved by independent mutations to proteins responsible for cell wall synthesis for FOS and in altering membrane dynamics for DAP. However, we did not observe genetic drivers that exhibited substantial cross-drug epistasis that could undermine DAP-FOS combination. Of interest was that FOS resistance in HOU503 was largely mediated by changes in phosphoenolpyruvate (PEP) flux as a result of mutations in pyruvate kinase (pyk). Increasing PEP flux could be a readily accessible mechanism for FOS resistance in many pathogens. Importantly, we show that HOU503 were able to develop DAP resistance through a variety of biochemical mechanisms and were able to employ different adaptive strategies. Finally, we showed that the addition of FOS can prolong the efficacy of DAP, significantly extending the timeline to resistance in vitro.

Physiological and biochemical mechanisms of the hen’s body recovery from dermanyssosis associated with deacarization

The purpose of the research is to study the efficacy of the insectoacaricide "5% D-cyphenotrine emulsion" against infestation of birds with Dermanyssus gallinae (dermanyssosis) after the deacarization of the poultry building and to characterize physiological and biochemical mechanisms of the recovery of Hy-Line hens after removed parasites.Materials and methods. A parasitological examination of the poultry farm found D. gallinae in one of the poultry buildings. Given positive results of the drug efficacy against the poultry red mite, we analyzed the morpho-physiological and physiological and biochemical parameters of the hen’s blood before and 10 and 20 days after the treatments. Changes in the ethological status of birds were recorded. We used 0.005% aqueous emulsion of "5% D-cyphenothrin emulsion" for treatment. To obtain it, the drug was diluted with water at a ratio of 1:1000 immediately before use.Results and discussion. After double treatment with "5% D-cyphenotrine emulsion" of the shop with hens from the test group, no live poultry red mite was found. Within 20 days after the disease reduction, representatives of this group showed high concentrations of cortisol which were 2.3–2.4 times (p < 0.001) higher than those of healthy hens. This indicates that the stress state of hens still remains after the parasitizing of D. gallinae. In addition, the recovery process takes a long time and with great stress for all systems of their body. This is also confirmed by a high level of lipid peroxidation. At the same time, high intensity of gluconeogenesis and, as a result, deterioration of lipid and protein metabolism were recorded in the hens in question. The positive results indicate an increasing need for additional energy expenditures which are paramount for the effective and well-timed implementation of adaptation mechanisms. It should be noted here that the values of all the above-mentioned indicators tend to normalize by the end of the study period. The changes noted in the blood of birds indicate the restoration of a number of body systems. The poultry red mite as an emergency factor affects the morphophysiology of the blood, in particular, the level of white blood cells, which is restored by the 10th day after deacarization, which triggers regenerative and reparative processes. There were also changes in the number of cells of the immune system, an increase in hemoglobin concentration to control values and optimization of behavior in representatives of the test group which are largely related to the normalized physiological activity of the thyroid gland after the poultry building deacarization. We found a partial recovery of the hen’s body systems after the poultry building deacarization with the drug "5% D-cyphenotrine emulsion", which is due to the long-term parasitizing of D. gallinae, a stressor of extreme strength.

Amino acid and biogenic amine adductions derived from reactive metabolites

: Reactive metabolites (RMs) are products generated from the metabolism of endogenous and exogenous substances. RMs are characterized as electrophilic species chemically reactive to nucleophiles. Those nucleophilic species may be nitrogen-containing bio-molecules, including macro-biomolecules, such as protein and DNA, and small biomolecules, i.e., amino acids (AAs) and biogenic amines (BAs). AAs and BAs are essential endogenous nitrogen-containing compounds required for normal development, metabolism, and physiological functions in organisms, through participating in the intracellular replication, transcription, translation, division and proliferation, DNA and protein synthesis, regulation of apoptosis, and intercellular communication activities. These biological amines containing an active lone pair of electrons on the electronegative nitrogen atom would be the proper N-nucleophiles to be attacked by the abovementioned RMs. This review covers an overview of adductions of AAs and BAs with varieties of RMs. These RMs are formed from metabolic activation of furans, naphthalene, benzene, and products of lipid peroxidation. This article is designed to provide readers with a better understanding of biochemical mechanisms of toxic action.

Current Role of Nanotechnology Used in Food Processing Industry to Control Food Additives and Exploring Their Biochemical Mechanisms

Background: With the advent of food additives centuries ago, the human race has found ways to improve and maintain the safety of utility, augment the taste, color, texture, nutritional value, and appearance of the food. Since the 19th century, when the science behind food spoilage was discerned, the use of food additives in food preservation has been increasing worldwide and at a fast pace to get along with modern lifestyles. Although food additives are thought to be used to benefit the food market, some of them are found to be associated with several health issues at an alarming rate. Studies are still going on regarding the mechanisms by which food additives affect public health. Therefore, an attempt has been made to find out the remedies by exploiting technologies that may convey new properties of food additives that can only enhance the quality of food without having any systemic side effects. Thus, this review focuses on the applications of nanotechnology in the production of nano-food additives and evaluates its success regarding reduction in the health-related hazards collaterally maintaining the food nutrient value. Methodology: Ahorough literature study was performed using scientific databases like PubMed, Science Direct, Scopus, Web of Science for determining the design of the study, and each article was checked for citation and referred to formulate the present review article. Conclusion: Nanotechnology can be applied in the food processing industry to control the unregulated use of food additives and to intervene in the biochemical mechanisms at a cellular and physiological level for the ensuring safety of food products. The prospective of nano-additive of chemical origin could be useful to reduce risks of hazards related to human health that are caused majorly due to the invasion of food contaminants (either intentional or non-intentional) into food, though this area still needs scientific validation. Therefore, this review provides comprehensive knowledge on different facets of food contaminants and also serves as a platform of ideas for encountering health risk problems about the design of improved versions of nano-additives.