Potential Therapeutic Aspects Research Articles

The Power of Karate: Exploring its Healing Potential, an assurance

Karate, a martial art that originated in Okinawa, Japan, holds immense potential beyond its reputation as a self-defense technique. This essay aims to explore the healing potential of karate, shedding light on various physical, mental, and emotional benefits associated with its practice. As graduate students, we understand the importance of expanding our horizons beyond the confines of academic pursuits, and exploring the potential therapeutic aspects of karate offers a unique perspective worth delving into.

The roles of trimethylamine-N-oxide in atherosclerosis and its potential therapeutic aspect: A literature review.

Current research supports the evidence that the gut microbiome (GM), which consist of gut microbiota and their biologically active metabolites, is associated with atherosclerosis development. Trimethylamine-N-oxide (TMAO), a metabolite produced by the GM through trimethylamine (TMA) oxidation, significantly enhances the formation and vulnerability of atherosclerotic plaques. TMAO promotes inflammation and oxidative stress in endothelial cells, leading to vascular dysfunction and plaque formation. Dimethyl-1-butanol (DMB), iodomethylcholine (IMC) and fluoromethylcholine (FMC) have been recognized for their ability to reduce plasma TMAO by inhibiting trimethylamine lyase, a bacterial enzyme involved in the choline cleavage anaerobic process, thus reducing TMA formation. Conversely, indole-3-carbinol (I3C) and trigonelline inhibit TMA oxidation by inhibiting flavin-containing monooxygenase-3 (FMO3), resulting in reduced plasma TMAO. The combined use of inhibitors of choline trimethylamine lyase and flavin-containing monooxygenase-3 could provide novel therapeutic strategies for cardiovascular disease prevention by stabilizing existing atherosclerotic plaques. This review aims to present the current evidence of the roles of TMA/TMAO in atherosclerosis as well as its potential therapeutic prevention aspects.

Mycorrhizal Colonization Modulates the Essential Oil Profile and Enzymatic and Non-Enzymatic Antioxidants to Mitigate the Adverse Effects of Water Deficit in Salvia subg. Perovskia.

Among traditional Iranian herbs, Perovskia species (a subgenus of Salvia), while being valued ornamentals, are also studied for numerous potential pharmacological and therapeutic aspects. The current study was conducted to assess the effectiveness of two species of arbuscular mycorrhizal fungi (AMF), Funneliformis mosseae and Rhizophagus intraradices, separately and in combination, in terms of the essential oil content and compositions along with the enzymatic and non-enzymatic antioxidants in Salvia abrotanoides and S. yangii in response to three levels of irrigation, including 100% FC as well-watered, 75% FC (moderate irrigation deficit), and 50% FC (severe irrigation deficit). In both species, essential oil content, enzyme antioxidant activities, total phenolics, and flavonoids were increased significantly with the severity of stress; this increase was more pronounced in mycorrhizal inoculated herbs. Furthermore, leaf phosphorus concentration, relative water content, chlorophylls a and b, and total carotenoids decreased in parallel with reducing soil moisture; albeit, AMF inoculation improved the stress symptoms under increasing severity of water restriction compared with their control conditions. In addition, the percentage of root colonization was positively correlated with the relative water content (RWC) and leaf phosphorus concentration. Taking into account the essential oil groups, AMF colonization elevated some essential oil components, such as oxygenated monoterpenes, 1,8-cineol, camphor, and borneol, whereas the main sesquiterpenes, including E-β-caryophyllene and α-humulene, remarkably decreased. Taken together, these findings highlighted the role of symbiosis with AMFs in increasing the tolerance of water deficit stress in S. abrotanoides and S. yangii and improving their essential oil composition.

Study of the Effects of Nicotine and Caffeine for the Treatment of Parkinson's Disease.

Parkinson's disease (PD) is considered to be a highly severe neurological disorder. PD occurs due to a decrease in dopamine production by the degeneration of dopamine-secreting neurons. Genetic mutations, environmental toxins and lifestyle are some of the risk factors of the progressive neurodegenerative disorder PD. Parkin protein, which is encoded by the PARK gene, is one of the important proteins, which is one of the causative agents. The Parkin protein has several mutations which lead to the development of the disease. Apart from PD, the mutations in Parkin also showed to be responsible for the onset of diseases like cancers. It is reported that the E28K mutation in the Ubl domain of parkin is highly deleterious and responsible for the onset of melanoma. This necessitates the development of new therapeutics against PD. Molecules like levodopa, carbidopa, monoamine oxidase type B inhibitors (MBO inhibitors), dopamine agonists, anticholinergics and amantadine are some commonly used drugs used to treat PD. Recently, there have been increasing evidence which shows that cigarette smoking and consumptions of coffee and tea could have important roles in modulating the risk of PD. Therefore, we planned to analyse the molecular mechanism of the binding interactions of nicotine, caffeine and the polyphenol ( -)-epigallocatechin-3-gallate (EGCG) from green tea with Parkin protein to predict their therapeutic potentials in PD targeting the E28K mutation. We focused on E28K mutant of Parkin as this mutant form of parkin has been shown to be the most pathogenic one. We could identify the potential therapeutic aspects of these natural products to prevent the onset of PD. This work may therefore be considered to be the first of its kind which would take into consideration the environmental toxicological approach in designing natural product inhibitors against the onset of PD.

Biomedical and Potential Therapeutic Aspects of Lithium Carbonate Use

Background: lithium carbonate salts are used in psychiatry for agitated states reduction and, above all, to prevent recurring manic and depressive episodes, as well as for the treatment of aggressive behavior. The pharmacological characteristics of lithium carbonate have not been fully studied. Recently, there has been an increasing interest in the wider use of Lithium carbonate, in particular, in the treatment of neurodegenerative diseases, and even in viral infections. Objective: to present an overview of the earliest and late foreign studies covering the biomedical and potential therapeutic aspects of lithium off-label use as follows for Alzheimer’s disease and viral infections. Material and methods: the keywords “lithium carbonate, neuroprotection, toxicity, Alzheimer’s disease, coronavirus infection” were used to search for scientic publications in the databases MEDLINE, PubMed, Scopus for the period 1970–2021. Conclusions: lithium carbonate can have signicant effects on pathogenesis of Alzheimer’s disease, which may be a good prospect in the treatment of this currently incurable disorder. It is also important to note the antiviral properties of lithium carbonate. Lithium carbonate is able to mitigate the immune-inammatory activation observed during episodes of bipolar disorder, including the normalization of cytokine levels. It is also important to note the antiviral capabilities of lithium carbonate. The most interesting is the direct impact of lithium carbonate on some members of the coronavirus family, which is especially important in connection with the real problems a global public health crisis associated with the SARS-CoV-2 virus.

Fasting in mood disorders and its potential therapeutic aspects -narrative review

Abstract Introduction: Fasting is defined as a period of voluntary abstinence from eating food for religious, therapeutic or political reasons, which is associated with a reduction in the supply of sources (kilocalories) to the body. There are different types of fasting, including short, long or intermittent fasting. It has been shown that the use of different types of fasting can influence the occurrence of mood disorders. The aim of this review was to search for the relationship between the use of fasting and mood disorders and its potential use as a therapeutic method. Material and method: The available literature was reviewed by searching the PubMed and Google Scholar databases using the following keywords: fasting, intermittent fasting, mood disorders, depression, Ramadan, for studies listed from database inception to November 2021. Results: A review of the collected scientific articles indicates that the dietary restrictions, including both daily restriction of caloric consumption and the use of intermittent fasting (IF), has potentially numerous health benefits in the co-treatment of mental diseases. However, due to conflicting results, further clinical trials in mentally ill people should be conducted. It is worth remembering that among patients with mental illnesses there are somatically ill. IF in these people may require additional nutritional modifications or discontinuation of therapy. Conclusions: Dietary restriction and fasting are promising methods in co-therapy of mood disorders treatment. However, implementing therapy needs earlier individual evaluation of their benefits and risk, the same as patient’s feasibility of implementing this type of intervention.

Lipid efflux mechanisms, relation to disease and potential therapeutic aspects

Lipids are hydrophobic and amphiphilic molecules involved in diverse functions such as membrane structure, energy metabolism, immunity, and signaling. However, altered intra-cellular lipid levels or composition can lead to metabolic and inflammatory dysfunction, as well as lipotoxicity. Thus, intra-cellular lipid homeostasis is tightly regulated by multiple mechanisms. Since most peripheral cells do not catabolize cholesterol, efflux (extra-cellular transport) of cholesterol is vital for lipid homeostasis. Defective efflux contributes to atherosclerotic plaque development, impaired β-cell insulin secretion, and neuropathology. Of these, defective lipid efflux in macrophages in the arterial walls leading to foam cell and atherosclerotic plaque formation has been the most well studied, likely because a leading global cause of death is cardiovascular disease. Circulating high density lipoprotein particles play critical roles as acceptors of effluxed cellular lipids, suggesting their importance in disease etiology. We review here mechanisms and pathways that modulate lipid efflux, the role of lipid efflux in disease etiology, and therapeutic options aimed at modulating this critical process.

Endothelial Progenitor Cells: New Targets for Therapeutics for Inflammatory Conditions With High Cardiovascular Risk.

Over the past decade, we have witnessed an exponential growth of interest into the role of endothelial progenitor cells (EPCs) in cardiovascular disease. While the major thinking revolves around EPC angiogenic repair properties, we have used a hypothesis-driven approach to discover disease-related defects in their characteristics and based on these findings, have identified opportunities for functional enhancement, which offer an exciting avenue for translation into clinical intervention. In this review, we focus on two groups; circulating myeloid angiogenic cells (MACs) and late outgrowth endothelial colony forming cells (ECFCs), and will discuss the unique properties and defects of each population, as new insights have been gained into the potential function of each sub-type using current techniques and multiomic technology. We will discuss their role in inflammatory disorders and alterations in mitochondrial function. In addition, we share key insights into the glycocalyx, and propose this network of membrane-bound proteoglycans and glycoproteins, covering the endothelium warrants further investigation in order to clarify its significance in ECFC regulation of vascularization and angiogenesis and ultimately for potential translational therapeutic aspects.

Microbiome and NAFLD: potential influence of aerobic fitness and lifestyle modification.

Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease with prevalence rates that are on the rise in the US and worldwide. NAFLD encompasses a spectrum of liver pathologies including simple steatosis to nonalcoholic steatohepatitis (NASH) with inflammation and fibrosis. The gut microbiome has emerged as a potential therapeutic target in combating metabolic diseases including obesity, Type 2 diabetes, and NAFLD/NASH. Diet-induced obesity/Western style diet feeding causes severe microbial dysbiosis initiating a microbiome signature that promotes metabolite production that directly impacts hepatic metabolism. Changes in lifestyle (i.e., diet, exercise, and aerobic fitness) improve NAFLD outcomes and can significantly influence the microbiome. However, directly linking lifestyle-induced remodeling of the microbiome to NAFLD pathogenesis is not well understood. Understanding the reshaping of the microbiome and the metabolites produced and their subsequent actions on hepatic metabolism are vital in understanding the gut-liver axis. In this review, we 1) discuss microbiome-derived metabolites that significantly contribute to the gut-liver axis and are directly linked to NAFLD/NASH and 2) present evidence on lifestyle modifications reshaping the microbiome and the potential therapeutic aspects in combating the disease.

Differential genotoxicity of diphenyl diselenide (PhSe)2and diphenyl ditelluride (PhTe)2

Organoselenium compounds have been pointed out as therapeutic agents. In contrast, the potential therapeutic aspects of tellurides have not yet been demonstrated. The present study evaluated the comparative toxicological effects of diphenyl diselenide (PhSe)2 and diphenyl ditelluride (PhTe)2 in mice after in vivo administration. Genotoxicity (as determined by comet assay) and mutagenicicity were used as end-points of toxicity. Subcutaneous administration of high doses of (PhSe)2 or (PhTe)2 (500 µmol/kg) caused distinct genotoxicity in mice. (PhSe)2 significantly decreased the DNA damage index after 48 and 96 h of its injection (p < 0.05). In contrast, (PhTe) caused a significant increase in DNA damage (p < 0.05) after 48 and 96 h of intoxication. (PhSe)2 did not cause mutagenicity but (PhTe)2 increased the micronuclei frequency, indicating its mutagenic potential. The present study demonstrated that acute in vivo exposure to ditelluride caused genotoxicity in mice, which may be associated with pro-oxidant effects of diphenyl ditelluride. In addition, the use of this compound and possibly other related tellurides must be carefully controlled.

Targeting P-selectin in acute pancreatitis

Importance of the field: Acute pancreatitis (AP) is a multifactorial disorder not fully understood yet. In particular, the pathogenetic pathways promoting a severe life-threatening course of AP are the subject of ongoing investigations. P-selectin has been shown to play a central role in the complex pathophysiology in AP as well as various other inflammatory conditions.Areas covered in this review: P-selectin function in AP is reviewed with focus on its dual function as a mediator of leukocyte recruitment and cell adhesion, which implies the unique effect of linking both inflammation and coagulation, especially in the progression from mild to severe necrotizing AP. Potential therapeutic aspects are discussed with regard to the clinical situation.What the reader will gain: A better understanding of the pathogenic role of P-selectin in AP and of the rationale for a therapeutic blockade.Take home message: P-selectin is a glycoprotein that mediates the adhesion of activated platelets and leukocytes to the vessel wall in various inflammatory conditions. Both pathophysiological steps are closely linked and play a key role in the course of severe AP. A treatment approach by inhibition of P-selectin could be of distinct interest as a therapeutic option in severe AP.

The Oncogenic Potential of Mesenchymal Stem Cells in the Treatment of Cancer: Directions for Future Research

Mesenchymal stem cells (MSCs) represent a promising new approach to the treatment of several diseases that are associated with dismal outcomes. These include myocardial damage, graft versus host disease, and possibly cancer. Although the potential therapeutic aspects of MSCs continue to be well-researched, the possible hazards of MSCs, and in particular their oncogenic capacity are poorly understood. This review addresses the oncogenic and tumor-supporting potential of MSCs within the context of cancer treatment. The risk for malignant transformation is discussed for each stage of the clinical lifecycle of MSCs. This includes malignant transformation in vitro during production phases, during insertion of potentially therapeutic transgenes, and finally in vivo via interactions with tumor stroma. The immunosuppressive qualities of MSCs, which may facilitate evasion of the immune system by a tumor, are also addressed. Limitations of the methods employed in clinical trials to date are reviewed, including the absence of long term follow-up and lack of adequate screening methods to detect formation of new tumors. Through discussions of the possible oncogenic and tumor-supporting mechanisms of MSCs, directions for future research are identified which may eventually facilitate the future clinical translation of MSCs for the treatment of cancer and other diseases.

Latinos and Latinas in Communal Settings: A Grounded Theory of Recovery

Semi-structured interviews were conducted with 12 Latino/a residents of a mutual help residential recovery program (Oxford House) in order to elicit their experiences of the program’s therapeutic elements. A model of recovery emerged from the analysis including several themes supported by existing literature: personal motivation and readiness to change, mutual help, sober environment, social support, and accountability. Consistent with a broad conceptualization of recovery, outcomes included abstinence, new life skills, and increased self-esteem/sense of purpose. Most participants were the only Latino/a in their Houses; however, cultural differences did not emerge as salient issues. The study’s findings highlight potential therapeutic aspects of mutual-help communal recovery programs and suggest that English-speaking, bicultural Latinos/as have positive experiences and may benefit from participating in these programs.

Circulating endothelial progenitor cells in cardiovascular disorders

The role of vascular endothelium in cardiovascular disorders is well recognized. Mature endothelial cells contribute to the repair of endothelial injury, but only with a limited capacity. This has led to growing interest and further investigation into circulating endothelial progenitor cells (EPCs) and their role in vascular healing, repair and postnatal neovascularization. Recent studies have shown that EPCs are affected both in number and function by several cardiovascular risk factors as well as various cardiovascular disease states. Here, we aim to provide an overview of EPCs in humans, from methods of assessment to quantification and functional properties in numerous cardiovascular conditions. In addition, we hope to offer some perspective on the potential diagnostic and therapeutic aspects of EPCs.

Role of gp130‐mediated signalling pathways in the heart and its impact on potential therapeutic aspects

IL-6-type cytokines bind to plasma membrane receptor complexes containing the common signal transducing receptor chain gp130 that is ubiquitously expressed in most tissues including the heart. The two major signalling cascades activated by the gp130 receptor, SHP2/ERK and STAT pathways, have been demonstrated to play important roles in cardiac development, hypertrophy, protection and remodelling in response to physiological and pathophysiological stimuli. Experimental data, both in vivo and in vitro, imply beneficial effects of gp130 signalling on cardiomyocytes in terms of growth and survival. In contrast, it has been reported that elevated serum levels of IL-6 cytokines and gp130 proteins are strong prognostic markers for morbidity and mortality in patients with heart failure or after myocardial infarction. Moreover, it has been shown that the local gp130 receptor system is altered in failing human hearts. In the present review, we summarize the basic principles of gp130 signalling, which requires simultaneous activation of STAT and ERK pathways under the tight control of positive and negative intracellular signalling modulators to provide a balanced biological outcome. Furthermore, we highlight the key role of the gp130 receptor and its major downstream effectors in the heart in terms of development and regeneration and in response to various physiological and pathophysiological stress situations. Finally, we comment on tissue-specific diversity and challenges in targeted pharmacological interference with components of the gp130 receptor system.

Medicinal Chemical and Pharmacological Aspects of Imidazole-Containing Histamine H3 Receptor Antagonists

The first antagonists known for the histamine H3 receptor were mono-substituted imidazole-containing compounds like thioperamide. Meanwhile numerous novel leads have been developed possessing improved affinities, selectivities, specificities, and pharmacokinetic properties. Scope and limitations of this promising class are discussed concerning their structure-activity relationships as well as pharmacological and potential therapeutic aspects.

E-30. The hallmarks of lung cancer

In a seminal article, Hanahan and Weinberg identified six hallmarks into which the vast majority of cancer related genomic and phenotypic changes may be classified [l]. In this presentation we will discuss how the genomic changes associated with lung cancers can be fitted into these hallmarks. Data are rapidly accumulating from a host of new technologies, both genomics and proteomics, and the use of suitable control tissues such as the establishment of immortalized but non malignant bronchial epithelial cell cultures will greatly assist our interpretation. Small cell (SCLC) and non-small cell (NSCLC) lung cancers share many common features as well as have unique molecular characteristics. Obviously the more than 100 changes described to date cannot be discussed in a few minutes. We will highlight some of the important recent discoveries as they relate to previously or recently identified genes, and discuss some of the potential clinical or therapeutic aspects of these findings. Some changes impact on multiple hallmarks, and alterations in one hallmark may affect others. For instance mutations of the ~53 gene impact on apoptosis, insensitivity to anti-growth signals and possibly other hallmarks. In addition, p53 mutations and several of the other genetic changes, individually or in aggregate lead to genomic instability which predisposes to further alterations. In addition, there is considerable crosstalk between components of the hallmarks. The hallmarks are as follows: Self sufficiency in growth signals. Tumor cells acquire the capacity to generate their own cell cycle signals. This is largely due to effects of dominant oncogenes, which include up regulation of HER2/neu, epidermal growth factor and myc While ras mutations are present in about 30% of adenocarcinomas, disruption of its signaling pathway is probably present in most or all lung cancers. Ras mutations are absent in SCLC. One reason may be because of the frequent methylation and silencing of the RASSFIA gene which binds ras in a GTP dependent manner, but which also functions as a transcription factor and induces apoptosis. While COX2 is up regulated in NSCLC, paradoxically, it is specifically down regulated in SCLC, raising the specter that COX2 inhibitors may prevent one form of lung cancer while stimulating another! Up regulation of the JAWSTAT pathway is another recently described phenomenon and occurs via multiple mechanisms including autocrine cytokine production as well as by loss of natural inhibitory proteins.

Œdème cérébral et insuffisance hépatique fulminante

Brain oedema leading to intracranial hypertension occurs in a significant proportion of patients with acute liver failure in whom it is a leading cause of death. Although precise pathogenic mechanisms associated to this severe complication remain incompletely understood, increasing evidence points to gut-derived neurotoxins including ammonia as key mediators in cerebral osmotic and perfusion disturbances. The management of brain oedema and intracranial hypertension requires a multidisciplinar approach in a center where liver transplantation is available, as this option is the only treatment modality that provides improvement in outcome. This article reviews the most common causes of acute liver failure and the standard of supportive care management, and describes future potential therapeutic aspects of brain oedema and intracranial hypertension.

Influence of interleukin-10 polymorphisms on interleukin-10 expression and survival in critically ill patients.

To determine the functionality of identified polymorphisms in the promoter and upstream regions of the interleukin-10 gene in terms of release of interleukin-10 from lipopolysaccharide-stimulated whole blood from healthy volunteers and to evaluate the relationship of interleukin-10 polymorphisms to interleukin-10 release, development of sepsis, and mortality in critically ill patients. Observational study. The academic unit of anesthesia and intensive care, university laboratories, and ten-bed general intensive care unit in a university teaching hospital. A total of 132 healthy volunteers plus 67 consecutive critically ill patients recruited within 24 hrs of admission to the intensive care unit, regardless of diagnosis. Plasma interleukin-10 levels were measured by enzyme-linked immunosorbent assay. Single nucleotide polymorphisms were detected by restriction fragment length polymorphism analysis. Dinucleotide repeat polymorphisms were identified after polymerase chain reaction using a DNA size analyzer. Stimulated interleukin-10 release in critically ill patients was significantly lower than in healthy subjects (p < .0001). In addition, in the patients who developed sepsis, interleukin-10 release at admission to the intensive care unit was significantly lower than in patients who did not subsequently develop sepsis (median [range] 1.47 [0.13-6.90] ng/mL compared with 4.93 [0.03-16.80] ng/mL, p = .001). The A allele of the single nucleotide polymorphism at -592 base pairs was associated with lower interleukin-10 release and higher mortality in critically ill patients. Other polymorphisms were not linked to interleukin-10 release, sepsis, or mortality. The A allele of the -592 base pair single nucleotide polymorphism in the interleukin-10 gene is associated with lower stimulated interleukin-10 release and increased mortality. Further investigations are required to determine the nature of the functionality and the potential diagnostic and therapeutic aspects of this marker.

Immunoregulatory functions of interleukin 18 and its role in defense against bacterial pathogens.

Interleukin-18 (IL-18) is a proinflammatory cytokine that belongs to the IL-1 cytokine family, due to its structure, receptor family and signal transduction pathways. Similarly to IL-1beta, IL-18 is synthesized as a precursor requiring caspase-1 for cleavage into an active IL-18 molecule. However, with regard to its capacity to induce the production of Th1 cytokines and to enhance cell-mediated cytotoxicity, IL-18 is also related to IL-12. Produced mainly by antigen-presenting cells, IL-18 is a pleiotropic factor involved in the regulation of both innate and acquired immune responses, playing a key role in autoimmune, inflammatory, and infectious diseases. This review summarizes recent advances in the understanding of IL-18 structure, processing, receptor expression, and immunoregulatory functions and emphasizes the critical role of this cytokine in bacterial infections. It focuses on the participation of this cytokine in the defense against intracellular bacteria, including Listeria, Shigella, Salmonella, and Mycobacterium tuberculosis. Since this cytokine may be particularly useful in immunoprophylactic and immunotherapeutic interventions in which the cellular response is most desirable, the potential therapeutic aspects of IL-18 is also discussed.