Human semen contains several trace elements such as calcium (Ca), copper (Cu), manganese (Mn), magnesium (Mg), zinc (Zn) and selenium (Se) which are necessary for reproductive health, normal spermatogenesis, sperm maturation, motility and capacitation, as well as normal sperm function. In this review, the potential role of these trace elements in male reproductive health, normal function of spermatozoa and fertility potency were considered. We selected and reviewed articles that considered crucial roles of trace elements in human sperm function and fertility. Ca is essential for sperm motility and its hyperactivation, sperm capacitation and acrosome reaction, as well as sperm chemotaxis. Sodium (Na) and potassium (K) are involved in sperm motility and capacitation. Mg is necessary for normal ejaculation, spermatogenesis and sperm motility. Zn is one of the most significant nutrients in human semen. Seminal deficiency of Zn can be associated with delayed testicular development, impaired spermatogenesis, deficiency of sex hormones, oxidative stress and inflammation, and apoptosis. Se is another significant element which has antioxidative properties and is essential for spermatogenesis and the maintenance of male fertility. Mn is a potent stimulator for sperm motility; however, increased level of seminal plasma Se can be toxic for sperm. Like Se, Cu has antioxidative properties and has a positive effect on sperm parameters. Decreased level of these trace elements can negatively affect human reproductive health, semen quality, sperm normal function and as the result, fertility potency in men. Measurement of these trace elements in men with idiopathic infertility is necessary.

Chronic obstructive pulmonary disease (COPD) is known as a progressive lung disease and the fourth leading cause of death worldwide. Despite valuable efforts, there is still no accurate diagnostic and prognostic tool for COPD. Hence, it seems that finding new biomarkers could contribute to provide better therapeutic platforms for COPD patients. Among various biomarkers, microRNAs (miRNAs) have emerged as new biomarkers for the prognosis and diagnosis of patients with COPD. It has been shown that deregulation of miRNAs targeting a variety of cellular and molecular pathways such as Notch, Wnt, hypoxia-inducible factor-1α, transforming growth factor, Kras, and Smad could be involved in COPD pathogenesis. Multiple lines of evidence have indicated that extracellular vesicles such as exosomes could carry a variety of cargos (i.e., mRNAs, miRNAs, and proteins) which transfer various cellular and molecular signals to recipient cells. Here, we summarized various miRNAs which could be applied as diagnostic and prognostic biomarkers in the treatment of patients with COPD. Moreover, we highlighted the role of extracellular vesicles containing miRNAs as diagnostic and prognostic biomarkers in COPD patients.

Zinc (Zn) is necessary for the normal function of the male reproductive system and spermatozoa. Although influences of zinc deficiency on impaired spermatogenesis and male infertility have been widely considered, the molecular and cellular mechanisms of these abnormalities are not well understood. General abnormalities, including hypogonadism, Leydig cells damage, deficiency of sex hormone production and impaired spermatogenesis, as well as inflammation, antioxidant depletion, sperm death and male infertility can be observed during zinc deficiency. However, it is not obvious which pathways are relevant to the pathogenesis of zinc deficiency. Oxidative stress (OS) induced by reactive oxygen species is likely as the main mechanism of zinc deficiency which is associated with sperm DNA fragmentation, decrease in sperm membrane integrity, apoptosis, depletion of antioxidants, and consequently poor sperm quality and male infertility. Therefore, identification of these pathways will give valuable information regarding the mechanisms of zinc deficiency on the male reproductive system and the potential way for developing a better clinical approach. In this review, we aim to discuss the proposed cellular and molecular mechanisms of zinc deficiency on the male reproductive system, the importance of OS and mechanisms by which zinc deficiency induces OS and depletion of other antioxidants.

Background/Aims: Semen hyperviscosity (SHV) is one of the significant factors involved in poor semen quality and male infertility. It also leads major problems during assisted reproduction techniques and in vitro fertilization process. Although influence of SHV on sperm quality, fertilization rate and male infertility have been widely considered, molecular and cellular mechanisms for these abnormalities are not well understood. In this review, we aimed to discuss the proposed cellular and molecular mechanisms of SHV on male reproductive system, the importance of oxidative stress (OS) and the mechanisms by which SHV induces OS and impairment of other antioxidants. Methods: A PubMed/Medline and EM-BASE search was performed using keywords: “hyperviscosity semen”, “oxidative stress”, and “male infertility”. Conclusion: OS induced by reactive oxygen species can be considered as a major mechanism in patients with hyperviscosity semen that is associated with DNA fragmentation, lipid peroxida-tion and sperm membrane disintegrity, apoptosis, depletion of antioxidants, and subsequently poor sperm quality and male infertility. Therefore, antioxidant therapy may improve main pathological effects of hyperviscosity semen, especially oxidative damages and inflammation, on sperm quality and function. Further, randomized controlled studies are necessary to confirm these results and make a comparison between effects of various antioxidants such as N-acethyl-cysteine and Curcumin on fertility problem in patients with hyperviscous semen.

Sulfur mustard (SM) is a chemical compound that preferentially targets ocular, cutaneous and pulmonary tissues. Although pathologic effect of SM has been extensively considered, molecular and cellular mechanism of its toxicity, especially at the chronic phase of injury is not well-understood. Excessive production of reactive oxygen species (ROS) and oxidative stress (OS) appears to be involved in SM-induced injuries. SM may trigger several molecular and cellular pathways linked to OS and inflammation that can subsequently result in cell death and apoptosis. At the acute phase of injury, SM can enhance ROS production and OS by reducing the activity of antioxidants, depletion of intercellular glutathione (GSH), decreasing the productivity of GSH-dependent antioxidants, mitochondrial deficiency, accumulation of leukocytes and pro-inflammatory cytokines. Overexpression of ROS producing enzymes and down-regulation of antioxidant enzymes are probably the major events by which SM leads to OS at the chronic phase of injury. Therefore, antioxidant therapy with potent antioxidants such as N-acetylcysteine and curcumin may be helpful to mitigate SM-induced OS damages. This review aims to discuss the proposed cellular and molecular mechanisms of acute and delayed SM toxicity, the importance of OS and mechanisms by which SM increases OS either at the acute or chronic phases of injuries along with research on antioxidant therapy as a suitable antidote.

Vincristine (VCR) is an important anti-cancer drug, which is highly toxic for the liver. This study aimed at evaluating the protective effect of alcoholic extract of saffron stigma against vincristine hepatotoxicity in the rat. A total number of 50 rats were randomly divided into 10 groups, including controls, rats receiving 0.25 mg/kg (A group), 0.5 mg/kg (B group), 0.75 mg/kg (C group) VCR, 0.25 mg/kg VCR + 0.5 mg/kg saffron (D group), 0.5 mg/kg VCR + 0.5 mg/kg saffron (E group), 0.75 mg/kg VCR + 0.5 mg/kg saffron (F group), 0.25 mg/kg VCR + 1mg/kg saffron (G group), 0.5 mg/kg VCR + 1 mg/kg saffron (H group), and 0.75 mg/kg VCR + 1 mg/kg saffron (I group) groups. Serum level of liver enzymes, including aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), and bilirubin were measured using specific kits at the end of the experimental period. Serum total antioxidant capacity (TAC) and malondialdehyde (MDA) values were measured using ferric reducing antioxidant of power (FRAP) and thiobarbituric acid reaction (TBAR) methods, respectively. Administration of VCR, especially at the concentration of 0.75mg/kg, caused severe hepatic injury with significant increase in the levels of AST (582.0±39.45 UI), ALT (124.0±5.92 UI), ALP (939.8±89.8 UI) enzymes and bilirubin (0.17±0.008). VCR administration also significantly increased the serum MDA level (0.49±0.021 nmol/ml), while TAC value was declined significantly (241.27±18.27 μmol/l). These effects were dose-dependent. Treatment with saffron extract decreased the activity of liver enzymes and MDA values in hepatotoxic rats with a significant enhancement in serum TAC content. These effects were notable for rats that received 1mg/kg plant extract. Administration of saffron, especially at higher concentration, can reduce VCR-induced hepatotoxicity, antioxidant depletion and lipid peroxidation, presumably due to its antioxidative properties.

Apoptosis is implicated in unfavorable remodeling of the left ventricle during acute myocardial infarction (AMI). Both DNA damage and p53 play important roles in regulating apoptosis. Expression patterns of apoptotic regulating genes such as p53, bax, and bcl-2 highlight the importance of inhibiting ventricle remodeling and subsequent injuries. In the present study, serum levels of p53 and 8-hydroxy-2-deoxyguanosine (8-OHdG) as well as p53, bax, and bcl-2 expression were examined after the onset of AMI in Iranian patients. Serum levels of p53 and 8-OHdG were measured by enzyme-linked immunosorbent assay (ELISA) and the presence of p53 protein and mRNA expression of p53, bax, and bcl-2 were analyzed by Western blotting and real time RT-PCR methods respectively. In patients presenting with AMI, serum levels of p53 and 8-OHdG were increased in comparison to healthy controls. Likewise, transcripts of p53 and bax were also elevated in patients while bcl-2 was decreased. Collectively, our data suggest the novel use of p53 and 8-OHdG as markers of apoptosis and DNA damage following AMI. Our results also revealed that apoptosis occurs in concert with an up-regulation of p53 and bax and a down-regulation of bcl-2 which may suggest a possible therapeutic intervention in patients recovering from AMI.© Versita Sp. z o.o.

MicroRNAs (miRNAs) are a novel class of small noncoding RNAs (ncRNAs) that play critical roles in regulation of gene expression, especially at posttranscriptional level. Over the past decade, the degree to which miRNAs are involved in male infertility has become clear. They are expressed in a cell- or phase-specific manner during spermatogenesis and play crucial role in male reproductive health. Therefore, dysregulation of miRNAs in testicular cells can be considered as a molecular basis for reproductive failure and male infertility. The abnormal expression pattern of miRNAs can be transmitted to the offspring via assisted reproductive techniques (ART) and results in the birth of children with a higher risk of infertility, congenital abnormalities, and morbidity. This review expounds on the miRNAs reported to play essential roles in somatic cells development, germ cells differentiation, steroidogenesis, normal spermatogenesis, sperm maturation, and male infertility, as well as emphasizes their importance as minimally invasive biomarkers of male infertility.