Redox Homeostasis, Gut Microbiota, and Epigenetics in Neurodegenerative Diseases: A Systematic Review.

Neurodegenerative diseases encompass a spectrum of disorders marked by the progressive degeneration of the structure and function of the nervous system. These conditions, including Parkinson's disease (PD), Alzheimer's disease (AD), Huntington's disease (HD), Amyotrophic lateral sclerosis (ALS), and Multiple sclerosis (MS), often lead to severe cognitive and motor deficits. A critical component of neurodegenerative disease pathologies is the imbalance between pro-oxidant and antioxidant mechanisms, culminating in oxidative stress. The brain's high oxygen consumption and lipid-rich environment make it particularly vulnerable to oxidative damage. Pro-oxidants such as reactive nitrogen species (RNS) and reactive oxygen species (ROS) are continuously generated during normal metabolism, counteracted by enzymatic and non-enzymatic antioxidant defenses. In neurodegenerative diseases, this balance is disrupted, leading to neuronal damage. This systematic review explores the roles of oxidative stress, gut microbiota, and epigenetic modifications in neurodegenerative diseases, aiming to elucidate the interplay between these factors and identify potential therapeutic strategies. We conducted a comprehensive search of articles published in 2024 across major databases, focusing on studies examining the relationships between redox homeostasis, gut microbiota, and epigenetic changes in neurodegeneration. A total of 161 studies were included, comprising clinical trials, observational studies, and experimental research. Our findings reveal that oxidative stress plays a central role in the pathogenesis of neurodegenerative diseases, with gut microbiota composition and epigenetic modifications significantly influencing redox balance. Specific bacterial taxa and epigenetic markers were identified as potential modulators of oxidative stress, suggesting novel avenues for therapeutic intervention. Moreover, recent evidence from human and animal studies supports the emerging concept of targeting redox homeostasis through microbiota and epigenetic therapies. Future research should focus on validating these targets in clinical settings and exploring the potential for personalized medicine strategies based on individual microbiota and epigenetic profiles.

Hydrogen Sulfide Modulation of Matrix Metalloproteinases and CD147/EMMPRIN: Mechanistic Pathways and Impact on Atherosclerosis Progression.

Atherosclerosis is a chronic inflammatory condition marked by endothelial dysfunction, lipid accumulation, inflammatory cell infiltration, and extracellular matrix (ECM) remodeling within arterial walls, leading to plaque formation and potential cardiovascular events. Key players in ECM remodeling and inflammation are matrix metalloproteinases (MMPs) and CD147/EMMPRIN, a cell surface glycoprotein expressed on endothelial cells, vascular smooth muscle cells (VSMCs), and immune cells, that regulates MMP activity. Hydrogen sulfide (H2S), a gaseous signaling molecule, has emerged as a significant modulator of these processes including oxidative stress mitigation, inflammation reduction, and vascular remodeling. This systematic review investigates the mechanistic pathways through which H2S influences MMPs and CD147/EMMPRIN and assesses its impact on atherosclerosis progression. A comprehensive literature search was conducted across PubMed, Scopus, and Web of Science databases, focusing on studies examining H2S modulation of MMPs and CD147/EMMPRIN in atherosclerosis contexts. Findings indicate that H2S modulates MMP expression and activity through transcriptional regulation and post-translational modifications, including S-sulfhydration. By mitigating oxidative stress, H2S reduces MMP activation, contributing to plaque stability and vascular remodeling. H2S also downregulates CD147/EMMPRIN expression via transcriptional pathways, diminishing inflammatory responses and vascular cellular proliferation within plaques. The dual regulatory role of H2S in inhibiting MMP activity and downregulating CD147 suggests its potential as a therapeutic agent in stabilizing atherosclerotic plaques and mitigating inflammation. Further research is warranted to elucidate the precise molecular mechanisms and to explore H2S-based therapies for clinical application in atherosclerosis.

Hydrogen Sulfide: An Emerging Regulator of Oxidative Stress and Cellular Homeostasis-A Comprehensive One-Year Review.

Hydrogen sulfide (H2S), traditionally recognized as a toxic gas, has emerged as a critical regulator in many biological processes, including oxidative stress and cellular homeostasis. This review presents an exhaustive overview of the current understanding of H2S and its multifaceted role in mammalian cellular functioning and oxidative stress management. We delve into the biological sources and function of H2S, mechanisms underlying oxidative stress and cellular homeostasis, and the intricate relationships between these processes. We explore evidence from recent experimental and clinical studies, unraveling the intricate biochemical and molecular mechanisms dictating H2S's roles in modulating oxidative stress responses and maintaining cellular homeostasis. The clinical implications and therapeutic potential of H2S in conditions characterized by oxidative stress dysregulation and disrupted homeostasis are discussed, highlighting the emerging significance of H2S in health and disease. Finally, this review underscores current challenges, controversies, and future directions in the field, emphasizing the need for further research to harness H2S's potential as a therapeutic agent for diseases associated with oxidative stress and homeostatic imbalance. Through this review, we aim to emphasize H2S's pivotal role in cellular function, encouraging further exploration into this burgeoning area of research.

Exploring the Potential Benefits of Natural Calcium-Rich Mineral Waters for Health and Wellness: A Systematic Review.

This systematic review investigates the potential health and wellness benefits of natural calcium-rich mineral waters. It emphasizes the importance of dietary calcium sourced from natural mineral waters in promoting bone health, maintaining cardiovascular function, aiding in weight management, and enhancing overall well-being. The review process involved the comprehensive analysis of peer-reviewed articles, clinical trials, and experimental studies published within the last decade. Findings reveal that consuming calcium-rich mineral water can contribute significantly to daily calcium intake, particularly for those with lactose intolerance or individuals adhering to plant-based diets. The unique bioavailability of calcium from such waters also appears to enhance absorption, thus potentially offering an advantage over other calcium sources. The potential benefits extend to the cardiovascular system, with some studies indicating a reduction in blood pressure and the prevalence of cardiovascular diseases. Emerging evidence suggests that calcium-rich mineral water might have a role in body weight management, though further research is needed. The review identifies several areas requiring additional research, such as the potential interaction between calcium-rich mineral water and other dietary components, the effects on populations with specific health conditions, and the long-term effects of consumption. In conclusion, natural calcium-rich mineral waters show promise as a readily accessible and bioavailable sources of dietary calcium, potentially beneficial for a broad range of individuals. However, further investigation is required to fully understand its range of health impacts and define optimal intake levels.

Lithium Biological Action Mechanisms after Ischemic Stroke.

Lithium is a source of great scientific interest because although it has such a simple structure, relatively easy-to-analyze chemistry, and well-established physical properties, the plethora of effects on biological systems-which influence numerous cellular and molecular processes through not entirely explained mechanisms of action-generate a mystery that modern science is still trying to decipher. Lithium has multiple effects on neurotransmitter-mediated receptor signaling, ion transport, signaling cascades, hormonal regulation, circadian rhythm, and gene expression. The biochemical mechanisms of lithium action appear to be multifactorial and interrelated with the functioning of several enzymes, hormones, vitamins, and growth and transformation factors. The widespread and chaotic marketing of lithium salts in potions and mineral waters, always at inadequate concentrations for various diseases, has contributed to the general disillusionment with empirical medical hypotheses about the therapeutic role of lithium. Lithium salts were first used therapeutically in 1850 to relieve the symptoms of gout, rheumatism, and kidney stones. In 1949, Cade was credited with discovering the sedative effect of lithium salts in the state of manic agitation, but frequent cases of intoxication accompanied the therapy. In the 1960s, lithium was shown to prevent manic and also depressive recurrences. This prophylactic effect was first demonstrated in an open-label study using the "mirror" method and was later (after 1970) confirmed by several placebo-controlled double-blind studies. Lithium prophylaxis was similarly effective in bipolar and also unipolar patients. In 1967, the therapeutic value of lithemia was determined, included in the range of 0.5-1.5 mEq/L. Recently, new therapeutic perspectives on lithium are connected with improved neurological outcomes after ischemic stroke. The effects of lithium on the development and maintenance of neuroprotection can be divided into two categories: short-term effects and long-term effects. Unfortunately, the existing studies do not fully explain the lithium biological action mechanisms after ischemic stroke.

Main Cations and Cellular Biology of Traumatic Spinal Cord Injury.

Traumatic spinal cord injury is a life-changing condition with a significant socio-economic impact on patients, their relatives, their caregivers, and even the community. Despite considerable medical advances, there is still a lack of options for the effective treatment of these patients. The major complexity and significant disabling potential of the pathophysiology that spinal cord trauma triggers are the main factors that have led to incremental scientific research on this topic, including trying to describe the molecular and cellular mechanisms that regulate spinal cord repair and regeneration. Scientists have identified various practical approaches to promote cell growth and survival, remyelination, and neuroplasticity in this part of the central nervous system. This review focuses on specific detailed aspects of the involvement of cations in the cell biology of such pathology and on the possibility of repairing damaged spinal cord tissue. In this context, the cellular biology of sodium, potassium, lithium, calcium, and magnesium is essential for understanding the related pathophysiology and also the possibilities to counteract the harmful effects of traumatic events. Lithium, sodium, potassium-monovalent cations-and calcium and magnesium-bivalent cations-can influence many protein-protein interactions, gene transcription, ion channel functions, cellular energy processes-phosphorylation, oxidation-inflammation, etc. For data systematization and synthesis, we used the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA) methodology, trying to make, as far as possible, some order in seeing the "big forest" instead of "trees". Although we would have expected a large number of articles to address the topic, we were still surprised to find only 51 unique articles after removing duplicates from the 207 articles initially identified. Our article integrates data on many biochemical processes influenced by cations at the molecular level to understand the real possibilities of therapeutic intervention-which must maintain a very narrow balance in cell ion concentrations. Multimolecular, multi-cellular: neuronal cells, glial cells, non-neuronal cells, but also multi-ionic interactions play an important role in the balance between neuro-degenerative pathophysiological processes and the development of effective neuroprotective strategies. This article emphasizes the need for studying cation dynamics as an important future direction.

Topical Reappraisal of Molecular Pharmacological Approaches to Endothelial Dysfunction in Diabetes Mellitus Angiopathy.

Diabetes mellitus (DM) is a frequent medical problem, affecting more than 4% of the population in most countries. In the context of diabetes, the vascular endothelium can play a crucial pathophysiological role. If a healthy endothelium-which is a dynamic endocrine organ with autocrine and paracrine activity-regulates vascular tone and permeability and assures a proper balance between coagulation and fibrinolysis, and vasodilation and vasoconstriction, then, in contrast, a dysfunctional endothelium has received increasing attention as a potential contributor to the pathogenesis of vascular disease in diabetes. Hyperglycemia is indicated to be the major causative factor in the development of endothelial dysfunction. Furthermore, many shreds of evidence suggest that the progression of insulin resistance in type 2 diabetes is parallel to the advancement of endothelial dysfunction in atherosclerosis. To present the state-of-the-art data regarding endothelial dysfunction in diabetic micro- and macroangiopathy, we constructed this literature review based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We interrogated five medical databases: Elsevier, PubMed, PMC, PEDro, and ISI Web of Science.

Recent Advances in Molecular Research on Hydrogen Sulfide (H2S) Role in Diabetes Mellitus (DM)-A Systematic Review.

Abundant experimental data suggest that hydrogen sulfide (H2S) is related to the pathophysiology of Diabetes Mellitus (DM). Multiple molecular mechanisms, including receptors, membrane ion channels, signalingmolecules, enzymes, and transcription factors, are known to be responsible for the H2S biological actions; however, H2S is not fully documented as a gaseous signaling molecule interfering with DM and vascular-linked pathology. In recent decades, multiple approaches regarding therapeutic exploitation of H2S have been identified, either based on H2S exogenous apport or on its modulated endogenous biosynthesis. This paper aims to synthesize and systematize, as comprehensively as possible, the recent literature-related data regarding the therapeutic/rehabilitative role of H2S in DM. This review was conducted following the "Preferred reporting items for systematic reviews and meta-analyses" (PRISMA) methodology, interrogating five international medically renowned databases by specific keyword combinations/"syntaxes" used contextually, over the last five years (2017-2021). The respective search/filtered and selection methodology we applied has identified, in the first step, 212 articles. After deploying the next specific quest steps, 51 unique published papers qualified for minute analysis resulted. To these bibliographic resources obtained through the PRISMA methodology, in order to have the best available information coverage, we added 86 papers that were freely found by a direct internet search. Finally, we selected for a connected meta-analysis eight relevant reports that included 1237 human subjects elicited from clinical trial registration platforms. Numerous H2S releasing/stimulating compounds have been produced, some being used in experimental models. However, very few of them were further advanced in clinical studies, indicating that the development of H2S as a therapeutic agent is still at the beginning.

COMBINED EFFECT OF THERMAL LOAD AND MECHANICAL LOAD IN TRANSTIBIAL PROSTHESIS. AN EMPIRICAL STUDY.

UNLABELLED: Probably the most important factor in evaluating a patient's prosthesis is quality of life. Transtibial amputations, are among the most frequently performed major limb amputations. Many individuals with transtibial amputations successfully achieve rehabilitation at or near their preamputation levels. Discomfort in prosthetic sockets continues to be a critical challenge faced by both prosthetists and amputees. MATERIAL AND METHODS: This paper proposes a fusion Graphic User Interface that combines two types of information (pressure and temperature). Data from pressure sensors and thermistors (an electrical resistor whose resistance is greatly reduced by heating, used for measurement and control) placed on the stump in transtibial prosthetics are collected in real time using a National Instruments Data Acquisition device. RESULTS: All the data stored in files are available for offline processing. The user has the possibility to analyse the signal by zooming or positioning the marker and window on different parts of signal. A complex analysis that involves the pressure and temperature for a location (where both sensors are placed) is available in time domain. CONCLUSIONS: Blunt-prosthesis interface is characterized by few parameters among the most important are pressure and friction. The action of these parameters during static and dynamic stage is very important because their actions can produce lesions of skin at the level of interface. Despite the advancements in surgical techniques and prostheses, much still needs to be done. We made certain that the sensors were in the same location by pressing on specific cells on the residual limb during various stages of the experimentation. The highest pressures recorded were during the stance phase of walking. The curve that shows the temperature evolution or pressure in one point could differ in different points from patient to patient.

GRAPHICAL USER INTERFACE WITH APPLICATIONS IN SUSCEPTIBLE-INFECTIOUS-SUSCEPTIBLE MODELS.

UNLABELLED: Practical significance of understanding the dynamics and evolution of infectious diseases increases continuously in contemporary world. The mathematical study of the dynamics of infectious diseases has a long history. AIM: By incorporating statistical methods and computer-based simulations in dynamic epidemiological models, it could be possible for modeling methods and theoretical analyses to be more realistic and reliable, allowing a more detailed understanding of the rules governing epidemic spreading. MATERIAL AND METHODS: To provide the basis for a disease transmission, the population of a region is often divided into various compartments, and the model governing their relation is called the compartmental model. To present all of the information available, a graphical user interface provides icons and visual indicators. The graphical interface shown in this paper is performed using the MATLAB software ver. 7.6.0. MATLAB software offers a wide range of techniques by which data can be displayed graphically. The process of data viewing involves a series of operations. To achieve it, I had to make three separate files, one for defining the mathematical model and two for the interface itself. RESULTS: Considering a fixed population, it is observed that the number of susceptible individuals diminishes along with an increase in the number of infectious individuals so that in about ten days the number of individuals infected and susceptible, respectively, has the same value. If the epidemic is not controlled, it will continue for an indefinite period of time. By changing the global parameters specific of the SIS model, a more rapid increase of infectious individuals is noted. CONCLUSIONS: Using the graphical user interface shown in this paper helps achieving a much easier interaction with the computer, simplifying the structure of complex instructions by using icons and menus, and, in particular, programs and files are much easier to organize. Some numerical simulations have been presented to illustrate theoretical analysis.

Analyse of socket-prosthesis-blunt complex for lower limb amputee using objective measure of patient's gait cycle.

UNLABELLED: The prosthetic application is a highly complex process. Modeling and simulation of biomechanics processes in orthopedics is a certainly field of interest in current medical research. Optimization of socket in order to improve the quality of patient's life is a major objective in prosthetic rehabilitation. A variety of numerical methods for prosthetic application have been developed and studied. MATERIAL AND METHODS: An objective method is proposed to evaluate the performance of a prosthetic patient according to surface pressure map over the residual limb. The friction coefficient due to various liners used in transtibial and transfemoral prosthesis is taken into account also. RESULTS: Creation of a bio-based modeling and mathematical simulation allows the design, construction and optimization of contact between the prosthesis cup and lack of functionality of the patient amputated considering the data collected and processed in real time and non-invasively. The von Mises stress distribution in muscle flap tissue at the bone ends shows a larger region subjected to elevated von Mises stresses in the muscle tissue underlying longer truncated bones. CONCLUSIONS: Finite element method was used to conduct a stress analysis and show the force distribution along the device. The results contribute to a better understanding the design of an optimized prosthesis that increase the patient's performance along with a god choice of liner, made by an appropriate material that fit better to a particular blunt. The study of prosthetic application is an exciting and important topic in research and will profit considerably from theoretical input. Interpret these results to be a permanent collaboration between math's and medical orthopedics.