Reactive Oxygen Species (ROS) and Male Fertility

Oxidative energy production is inevitably associated with the generation of reactive oxygen species (ROS), excessive concentrations of which can lead to cellular pathology. A free radical may be defined as any molecule that has one or more unpaired electrons. The superoxide anion, the hydroxyl radical, and the hypochlorite radical are some of the highest reactive radicals of oxygen. Owing to their high reactivity and to their capability of initiating an uncontrolled cascade of chain reactions, ROS produce extensive protein damage and cytoskeletal modifications and inhibit cellular mechanisms. Aerobic organisms are equipped with a powerful battery of mechanisms that protect them from the adverse effects of lipid peroxidation (LPO) and other manifestations of oxygen toxicity. Defective sperm function frequently causes male infertility, due to abnormal flagella movement, failure to recognize the zona, and inhibition of sperm-oocyte fusion. ROS are fundamental mediators of physiological sperm function, such as signal transduction mechanisms that have an effect on fertility. ROS can have positive effects on sperm and the concentration functions depending on the nature and the concentration of the ROS involved. They are necessary in regulating the hyperactivation and the ability of the spermatozoa to undergo acrosome reaction. An increased amount of superoxide anion (O2-) is one of the first steps required by the spermatozoa for induction and development of hyperactivation and capacitation. Numerous studies have shown that oxidative stress plays an important role in the pathophysiology of infertility and assisted fertility. The paternal genome is of primary importance in the normal embryo and fetal development. ROS-induced sperm damage during sperm translation, such as signal transduction through the seminiferous tubules and epididymis, is one of the most important mechanisms leading to sperm DNA damage. Male germ cells are extremely vulnerable to oxidative stress as the sperm membrane is rich in unsaturated fatty acids and lacks the capacity for DNA repair. Spermatozoa are particularly susceptible to ROS-induced damage because their plasma membranes contain large quantities of polyunsaturated fatty acids (PUFA) and their cytoplasm contains low concentrations of the scavenging enzymes. Many clinical and research institutes are investigating the usefulness of antioxidant supplementation and their role in prevention of the infertility problems. Incubation under oxygen in vitro was detrimental to human spermatozoa, decreasing motility and viability. Since then, many reports have associated ROS with impaired sperm function, including decreased motility, abnormal morphology, and decreased sperm-egg penetration. Increasing knowledge of the mechanisms whereby ROS and endogenous antioxidant systems influence reproductive processes can assist to optimize the application of exogenous antioxidants to fertility treatment

Sirtuins and redox signaling interplay in neurogenesis, neurodegenerative diseases, and neural cell reprogramming

Since the discovery of Neural Stem Cells (NSCs) there are still mechanism to be clarified, such as the role of mitochondrial metabolism in the regulation of endogenous adult neurogenesis and its implication in neurodegeneration. Although stem cells require glycolysis to maintain their stemness, they can perform oxidative phosphorylation and it is becoming more and more evident that mitochondria are central players, not only for ATP production but also for neuronal differentiation's steps regulation, through their ability to handle cellular redox state, intracellular signaling, epigenetic state of the cell, as well as the gut microbiota-brain axis, upon dietary influences. In this scenario, the 8-oxoguanine DNA glycosylase (OGG1) repair system would link mitochondrial DNA integrity to the modulation of neural differentiation. On the other side, there is an increasing interest in NSCs generation, from induced pluripotent stem cells, as a clinical model for neurodegenerative diseases (NDs), although this methodology still presents several drawbacks, mainly related to the reprogramming process. Indeed, high levels of reactive oxygen species (ROS), associated with telomere shortening, genomic instability, and defective mitochondrial dynamics, lead to pluripotency limitation and reprogramming efficiency's reduction. Moreover, while a physiological or moderate ROS increase serves as a signaling mechanism, to activate differentiation and suppress self-renewal, excessive oxidative stress is a common feature of NDs and aging. This ROS-dependent regulatory effect might be modulated by newly identified ROS suppressors, including the NAD(+)-dependent deacetylase enzymes family called Sirtuins (SIRTs). Recently, the importance of subcellular localization of NAD synthesis has been coupled to different roles for NAD in chromatin stability, DNA repair, circadian rhythms, and longevity. SIRTs have been described as involved in the control of both telomere's chromatin state and expression of nuclear gene involved in the regulation of mitochondrial gene expression, as well as in several NDs and aging. SIRTs are ubiquitously expressed in the mammalian brain, where they play important roles. In this review we summarize the current knowledge on how SIRTs-dependent modulation of mitochondrial metabolism could impact on neurogenesis and neurodegeneration, focusing mainly on ROS function and their role in SIRTs-mediated cell reprogramming and telomere protection

Redoxomics and Oxidative Stress: From the Basic Research to the Clinical Practice

Potentially oxidant chemical species, which include not only free radicals but also other oxidizing chemical species such as reactive oxygen species (ROS), for example, hydroxyl radical and hydrogen peroxide, and nitrogen reactive species (RNS), for example, nitric oxide, play a relevant role in all biological processes and especially in cell defenses and molecular signaling. Their action is finely modulated by the antioxidant network that is composed either by endogenous or exogenous compounds (e.g., enzymes, peptides, lipids, and vitamins). An impaired modulation of oxidant species can lead to the so-called oxidative stress that is now considered an emerging health risk factor in almost all living organisms including plants, animals, and humans. Indeed, oxidative stress is related to a reduced lifespan and many diseases (e.g., cardiovascular diseases, neurodegenerative disorders, and metabolic diseases) both in humans and in animals. Unfortunately, oxidative stress does not show any clinical picture, but it can be detected only by means of specific laboratory tests. The recent recognition of a specific “redox code” and the definition of a redoxomics as a new “omics” are now enlarging the horizon of the traditional oxidative stress field leading to the definition of the so-called electrophilic stress. The aim of this chapter is to review the basic principles of redox reaction starting from the concept of free radicals and antioxidant in order to define the “electrophilic stress” as an emerging health risk factor for early aging and almost 1000 illness from infectious diseases to cancer. A paragraph is dedicated to the tests to measure oxidative stress in clinical practice either in humans or in animals in order to prevent, to treat and to monitor electrophilic-related diseases

Oxidative Imbalance in HIV-1 Infected Patients Treated with Antiretroviral Therapy

It is generally accepted that oxidative stress is involved in HIV infection. However, the role in oxidative balance of Highly Active Antiretroviral Therapy (HAART) is still debated. In our study we assessed serum oxidant and antioxidant levels in an HIV-1-infected population treated with HAART, and compared them with those of untreated HIV-1 patients and HIV-1-negative subjects. The study included 116 HIV-1-infected patients (86 HAART-treated and 30 untreated), and 46 HIV-negative controls. Serum oxidant levels were significantly higher in the HIV-1 treated group as compared to untreated and control groups. In addition, a decrease of serum total antioxidant status was observed in the HIV-1 treated group. To be noted is that patients who rigorously follow antiretroviral therapy (optimal HAART adherence) have significantly higher oxidative status than those who do not closely follow the therapy (poor HAART adherence). Analysis of variance revealed no significant further increase in oxidative status in HIV-1-infected patients taking antiretroviral and other drugs with the exception of psychiatric drugs (e.g. anxiolytics or antidepressants). Taken together, our results indicate that HAART may affect oxidative stress in HIV-1-infected patients and suggest that antiretroviral therapy plays an important role in the synergy of HIV infection and oxidative stress

A pilot study on the efficacy of a seaweed mud application in the treatment of cellulite

Background: Cellulite represents a common multi-factorial condition that affects nearly all women and is now recognized as a clinical condition associated with systemic factors and negative psychological effects. Several noninvasive and minimally invasive treatments were developed during the last few years, but limited evidence supports many of them due to lack of evidence, insufficient participants, and potential adverse effects. Methods: This study aimed to evaluate the efficacy of a seaweed mud application in improving both the structure and function of tissues affected by cellulite. Sixty women with cellulite underwent 4-week applications of seaweed mud on the buttocks and thighs. The following assessments were performed at baseline and after the last treatment: photographic, clinical, and anthropometric evaluation; tests for elasticity and hydration; ultrasonography of cellulite nodules; and cellulite biopsies in the trochanteric region. Patient satisfaction was assessed using a 5-point Likert-scale questionnaire. Results: The treatment resulted in a significant improvement in the severity of cellulite severity between the initial assessment and the 4-week follow-up, with enhanced structure, elasticity, and hydration of the affected tissues. Microscopic analysis of the cellulite biopsies revealed a significant restoration of dermal organization with induced collagen synthesis and reduced inflammation, edema, and lipid deposition following the 4-week seaweed mud applications. Additionally, the treatment led to a remarkable improvement in comfort and satisfaction as well as a reduction in body circumferences. Conclusions: The cosmetic application of seaweed mud has proven to be a safe, non-invasive treatment for improving the tissue alterations characteristic of cellulite

Gluteal femoral subcutaneous and dermal adipose tissue in female

Background: During the sexual maturation, gluteal femoral adipose tissue is subjected to numerous modifications, not observable in other regions, in particular in women and less in men. Other authors described this region, but they used imaging techniques having lower resolution, than MRI proposed in this study. High resolution imaging techniques might provide important and more detailed information about the anatomy of gluteal femoral region. Methods: This study has been performed using 7 T-magnetic resonance imaging and ultrastructural analysis in order to provide accurate description of the subcutaneous adipose tissue and dermis of gluteal femoral region. In this study specimens harvested from cadavers and form living patients have been analyzed. Results: The results showed the presence of three layers: superficial, middle, and deep, characterized by different organization of fat lobules. High resolution imaging showed the adipose papilla that originates from dermis and protrude in subcutaneous adipose tissue. Adipose papilla is characterized by a peculiar morphology with a basement, a neck and a head and these elements represent the functional subunits of adipose papilla. Moreover, ultrastructural study evidenced the relationship between adipocytes and sweat glands, regulated by lipid vesicles. Conclusions: This study provides important information about subcutaneous and dermal fat anatomy of gluteal femoral region, improving the past knowledge, and move toward a better understanding of the cellulite physiopathology

Search for new particles in events with energetic jets and large missing transverse momentum in proton-proton collisions at root s=13 TeV

A search is presented for new particles produced at the LHC in proton-proton collisions at root s = 13 TeV, using events with energetic jets and large missing transverse momentum. The analysis is based on a data sample corresponding to an integrated luminosity of 101 fb(-1), collected in 2017-2018 with the CMS detector. Machine learning techniques are used to define separate categories for events with narrow jets from initial-state radiation and events with large-radius jets consistent with a hadronic decay of a W or Z boson. A statistical combination is made with an earlier search based on a data sample of 36 fb(-1), collected in 2016. No significant excess of events is observed with respect to the standard model background expectation determined from control samples in data. The results are interpreted in terms of limits on the branching fraction of an invisible decay of the Higgs boson, as well as constraints on simplified models of dark matter, on first-generation scalar leptoquarks decaying to quarks and neutrinos, and on models with large extra dimensions. Several of the new limits, specifically for spin-1 dark matter mediators, pseudoscalar mediators, colored mediators, and leptoquarks, are the most restrictive to date.Peer reviewe

The biological and molecular action of ozone and its derivatives: state-of-the-art, enhanced scenarios, and quality insights

The ultimate objective of this review is to encourage a multi-disciplinary and integrated methodological approach that, starting from the recognition of some current uncertainties, helps to deepen the molecular bases of ozone treatment effects on human and animal well-being and to optimize their performance in terms of reproducibility of results, quality, and safety. In fact, the common therapeutic treatments are normally documented by healthcare professionals’ prescriptions. The same applies to medicinal gases (whose uses are based on their pharmacological effects) that are intended for patients for treatment, diagnostic, or preventive purposes and that have been produced and inspected in accordance with good manufacturing practices and pharmacopoeia monographs. On the contrary, it is the responsibility of healthcare professionals, who thoughtfully choose to use ozone as a medicinal product, to achieve the following objectives: (i) to understand the molecular basis of the mechanism of action; (ii) to adjust the treatment according to the clinical responses obtained in accordance with the principles of precision medicine and personalized therapy; (iii) to ensure all quality standards. © 2023 by the authors

Pilot study of histology aspect of cellulite in seventy patients who differ in BMI and cellulite grading

Cellulite is a topographic alteration of the skin with unknown etiology and is characterized by the presence of a dimpled or puckered aspect, as resembling an orange peel and cottage cheese or as having mattress-like appearance