Obesity and Male Reproduction: Do Sirtuins Play a Role?

Obesity is a major current public health problem of global significance. A progressive sperm quality decline, and a decline in male fertility, have been reported in recent decades. Several studies have reported a strict relationship between obesity and male reproductive dysfunction. Among the many mechanisms by which obesity impairs male gonadal function, sirtuins (SIRTs) have an emerging role. SIRTs are highly conserved nicotinamide adenine dinucleotide (NAD+)-dependent deacetylases that play a role in gene regulation, metabolism, aging, and cancer. SIRTs regulate the energy balance, the lipid balance, glucose metabolism, and adipogenesis, but current evidence also indicates a role for SIRTs in male reproduction. However, the majority of the studies have been conducted in animal models and very few have been conducted with humans. This review shows that SIRTs play an important role among the molecular mechanisms by which obesity interferes with male fertility. This highlights the need to deepen this relationship. It will be of particular interest to evaluate whether synthetic and/or natural compounds capable of modifying the activity of SIRTs may also be useful for the treatment of obesity and its effects on gonadal function. Although few studies have explored the role of SIRT activators in obesity-induced male infertility, some molecules, such as resveratrol, appear to be effective in modulating SIRT activity, as well as counteracting the negative effects of obesity on male fertility. The search for strategies to improve male reproductive function in overweight/obese patients is a challenge and understanding the role of SIRTs and their activators may open new interesting scenarios in the coming years.     

Cellular and Molecular Signatures of Oxidative Stress in Bronchial Epithelial Cell Models Injured by Cigarette Smoke Extract

Exposure of the airways epithelium to environmental insults, including cigarette smoke, results in increased oxidative stress due to unbalance between oxidants and antioxidants in favor of oxidants. Oxidative stress is a feature of inflammation and promotes the progression of chronic lung diseases, including Chronic Obstructive Pulmonary Disease (COPD). Increased oxidative stress leads to exhaustion of antioxidant defenses, alterations in autophagy/mitophagy and cell survival regulatory mechanisms, thus promoting cell senescence. All these events are amplified by the increase of inflammation driven by oxidative stress. Several models of bronchial epithelial cells are used to study the molecular mechanisms and the cellular functions altered by cigarette smoke extract (CSE) exposure, and to test the efficacy of molecules with antioxidant properties. This review offers a comprehensive synthesis of human in-vitro and ex-vivo studies published from 2011 to 2021 describing the molecular and cellular mechanisms evoked by CSE exposure in bronchial epithelial cells, the most used experimental models and the mechanisms of action of cellular antioxidants systems as well as natural and synthetic antioxidant compounds.     

The Role of Chemokines in the Development of Gastric Cancer—Diagnostic and Therapeutic Implications

Gastric cancer (GC) is the fifth most common cancer worldwide and the second leading cause of cancer-related death. GC is usually diagnosed at an advanced stage due to late presentation of symptoms. Therefore, there is a need for establishing more sensitive and specific markers useful in early detection of the disease when a cancer is asymptomatic to improve the diagnostic and clinical decision-making process. Some researchers suggest that chemokines and their specific receptors play an important role in GC initiation and progression via promotion of angiogenesis, tumor transformation, invasion, survival and metastasis as well as protection from host response and inter-cell communication. Chemokines are small proteins produced by various cells such as endothelial cells, fibroblasts, leukocytes, and epithelial and tumor cells. According to our knowledge, the significance of chemokines and their specific receptors in diagnosing GC and evaluating its progression has not been fully elucidated. The present article offers a review of current knowledge on general characteristics of chemokines, specific receptors and their role in GC pathogenesis as well as their potential usefulness as novel biomarkers for GC.     

Premature Termination Codon in 5′ Region of Desmoplakin and Plakoglobin Genes May Escape Nonsense-Mediated Decay through the Reinitiation of Translation

Arrhythmogenic cardiomyopathy is a heritable heart disease associated with desmosomal mutations, especially premature termination codon (PTC) variants. It is known that PTC triggers the nonsense-mediated decay (NMD) mechanism. It is also accepted that PTC in the last exon escapes NMD; however, the mechanisms involving NMD escaping in 5′-PTC, such as reinitiation of translation, are less known. The main objective of the present study is to evaluate the likelihood that desmosomal genes carrying 5′-PTC will trigger reinitiation. HL1 cell lines were edited by CRISPR/Cas9 to generate isogenic clones carrying 5′-PTC for each of the five desmosomal genes. The genomic context of the ATG in-frame in the 5′ region of desmosomal genes was evaluated by in silico predictions. The expression levels of the edited genes were assessed by Western blot and real-time PCR. Our results indicate that the 5′-PTC in PKP2, DSG2 and DSC2 acts as a null allele with no expression, whereas in the DSP and JUP gene, N-truncated protein is expressed. In concordance with this, the genomic context of the 5′-region of DSP and JUP presents an ATG in-frame with an optimal context for the reinitiation of translation. Thus, 5′-PTC triggers NMD in the PKP2, DSG2* and DSC2 genes, whereas it may escape NMD through the reinitiation of the translation in DSP and JUP genes, with no major effects on ACM-related gene expression.     

Cation Permeability of Voltage-Gated Hair Cell Ca2+ Channels of the Vertebrate Labyrinth

Some hearing, vestibular, and vision disorders are imputable to voltage-gated Ca²⁺ channels of the sensory cells. These channels convey a large Ca²⁺ influx despite extracellular Na⁺ being 70-fold more concentrated than Ca²⁺; such high selectivity is lost in low Ca²⁺, and Na⁺ can permeate. Since the permeation properties and molecular identity of sensory Ca²⁺ channels are debated, in this paper, we examine the Na⁺ current flowing through the L- and R-type Ca²⁺ channels of labyrinth hair cells. Ion currents and cytosolic free Ca²⁺ concentrations were simultaneously monitored in whole-cell recording synchronous to fast fluorescence imaging. L-type and R-type channels were present with different densities at selected sites. In 10 nM Ca²⁺, the activation and deactivation time constants of the L-type Na⁺ current were accelerated and its maximal amplitude increased by 6-fold compared to physiological Ca²⁺. The deactivation of the R-type Na⁺ current was not accelerated, and its current amplitude increased by 2.3-fold in low Ca²⁺; moreover, it was partially blocked by nifedipine in a voltage- and time-dependent manner. In conclusion, L channel gating is affected by the ion species permeating the channel, and its selectivity filter binds Ca²⁺ more strongly than that of R channel; furthermore, external Ca²⁺ prevents nifedipine from perturbing the R selectivity filter.     

Pain Modulation from the Locus Coeruleus in a Model of Hydrocephalus: Searching for Oxidative Stress-Induced Noradrenergic Neuroprotection

Pain transmission at the spinal cord is modulated by noradrenaline (NA)-mediated actions that arise from supraspinal areas. We studied the locus coeruleus (LC) to evaluate the expression of the cathecolamine-synthetizing enzyme tyrosine hydroxylase (TH) and search for local oxidative stress and possible consequences in descending pain modulation in a model of hydrocephalus, a disease characterized by enlargement of the cerebral ventricular system usually due to the obstruction of cerebrospinal fluid flow. Four weeks after kaolin injection into the cisterna magna, immunodetection of the catecholamine-synthetizing enzymes TH and dopamine-β-hydroxylase (DBH) was performed in the LC and spinal cord. Colocalization of the oxidative stress marker 8-OHdG (8-hydroxyguanosine; 8-OHdG), with TH in the LC was performed. Formalin was injected in the hindpaw both for behavioral nociceptive evaluation and the immunodetection of Fos expression in the spinal cord. Hydrocephalic rats presented with a higher expression of TH at the LC, of TH and DBH at the spinal dorsal horn along with decreased nociceptive behavioral responses in the second (inflammatory) phase of the formalin test, and formalin-evoked Fos expression at the spinal dorsal horn. The expression of 8-OHdG was increased in the LC neurons, with higher co-localization in TH-immunoreactive neurons. Collectively, the results indicate increased noradrenergic expression at the LC during hydrocephalus. The strong oxidative stress damage at the LC neurons may lead to local neuroprotective-mediated increases in NA levels. The increased expression of catecholamine-synthetizing enzymes along with the decreased nociception-induced neuronal activation of dorsal horn neurons and behavioral pain signs may indicate that hydrocephalus is associated with alterations in descending pain modulation.     

Lutein: a valuable ingredient of fruit and vegetables

Lutein is a human serum carotenoid which is not synthesized by humans and thus must be obtained by the ingestion of food containing it such as fruits and vegetables. Lutein is present in different forms in those foods as all-trans-lutein, cis-lutein, epoxi-lutein, and lutein linked to proteins. It discusses if the intake of lutein or diets supplemented with lutein or diets rich in fruits and vegetables are important in the prevention of diseases like some cancers, cardiovascular diseases, etc., that may be affected by the antioxidant effect of lutein; or in the prevention of age-related macular degeneration and other eye diseases. The concentration of lutein in fruits and vegetables depends on the species. We've included the concentration of lutein in 74 species reported by different authors since 1990. Currently the quantification of lutein is mainly performed by HPLC, but more investigations into a quantification method for lutein, lutein isomers, and epoxi-lutein are necessary. Improvement of lutein extraction methods is important as well. Methods commonly used in the vegetable and fruit industry like heat treatment, storage conditions, etc. can change lutein concentrations; other factors depend on the plant, for instance the variety, the stage of maturity, etc.     

Effects of SARS-CoV-2 Inflammation on Selected Organ Systems of the Human Body

Introduction and purpose of the study: SARS-CoV-2 virus does not only affect the respiratory system. It may cause damage to many organ systems with long-term effects. The latest scientific reports inform that this virus leaves a long-term trace in the nervous, circulatory, respiratory, urinary and reproductive systems. It manifests itself in disturbances in the functioning of the organs of these systems, causing serious health problems. The aim of the study was to review the latest research into the long-term effects of COVID-19 and determine how common these symptoms are and who is most at risk. Based on a literature review using the electronic scientific databases of PubMed and Web of Science on the long-term effects of SARS-CoV-2 infection, 88 studies were included in the analysis. The information contained in the analyzed literature shows that the SARS-CoV-2 virus can cause multi-organ damage, causing a number of long-term negative health complications. Conclusions: There is evidence that the virus can cause long-term complications lasting more than six months. They mainly concern disturbances in the functioning of the nervous, circulatory and respiratory systems. However, these studies are small or short-lasting, and many are speculative.