Features of Pathobiology and Clinical Translation of Approved Treatments for Coronavirus Disease 2019.

BACKGROUND: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is currently the most important etiological agent of acute respiratory distress syndrome (ARDS) with millions of infections and deaths in the last 2 years worldwide. Several reasons and parameters are responsible for the difficult management of coronavirus disease-2019 (COVID-19) patients; the first is virus behavioral factors such as high transmission rate, and the different molecular and cellular mechanisms of pathogenesis remain a matter of controversy, which is another factor. SUMMARY: In the present review, we attempted to explain about features of SARS-COV-2, particularly focusing on the various aspects of pathogenesis and treatment strategies. KEY MESSAGES: We note evidence for the understanding of the precise molecular and cellular mechanisms of SARS-CoV-2 pathogenesis, which can help design the appropriate drug or vaccine. Additionally, and importantly, we reported the updated issues associated with the history and development of treatment strategies such as, drugs, vaccines, and other medications that have been approved or under consideration in clinics and markets worldwide.

Association of the human aryl hydrocarbon receptor repressor (AhRR)-c.565C>G transversion with male infertility: A case-control study from Iran.

Dioxins (eg, 2,3,7,8-tetrachlorodibenzo-p-dioxin/TCDD), as environmental endocrine disruptors and toxic carcinogens, can affect male reproductive health. The influence of dioxins is mediated via the aryl hydrocarbon receptor (AhR) pathway and its repressor (AhRR). In this study, we investigated the association of AhRR-c.565C>G transversion polymorphism with male infertility. In a hospital-based case-control study, 221 semen samples (111 infertile and 110 healthy controls) based on World Health Organization guidelines were collected from in vitro fertilization centers of Babol, Iran. The AhRR-c.565C>G (rs2292596) polymorphism was genotyped using a polymerase chain reaction-restriction fragment length polymorphism analysis. The difference in the allele frequency of AhRR-c.565C>G transversion polymorphism did not reach a significant level. The genotype frequency was statistically significantly different between fertile and infertile men. We found that polymorphism rs2292596 (Pro185Ala) was statistically significantly associated with the risk of male infertility. In addition, the statistical difference became more significant when the frequency was compared between the Pro/Pro genotype and the Pro/Ala plus Ala/Ala genotype. The 185 Pro wild-type alleles of AhRR may be associated with the risk of male infertility. The proallele also may diminish inhibition of AhR-mediated signaling of exposure to environmental pollutants.

Zinc is an Essential Element for Male Fertility: A Review of Zn Roles in Men's Health, Germination, Sperm Quality, and Fertilization.

Zinc (Zn) is the second most abundant trace element in human, which can't be stored in the body, thus regular dietary intake is required. This review explained the physiological and pathogenesis roles of zinc in men's health and its potentials in germination, quality of sperm, and fertilization. Our investigation showed that Zn contained many unique properties in human, especially males. The antioxidant quality is one of them. Also, the increased reactive oxygen species levels in the seminal plasma of men who are both infertile and smokers influence the Zn content of seminal plasma in a way that physiology of spermatozoa can be affected as well. Moreover, Zn acts as a toxic repercussionagainst heavy metals and cigarette inflammatory agents. Zinc as a hormone balancer helps hormones such as testosterone, prostate and sexual healthand functions as an antibacterial agent in men's urea system. It plays a role in epithelial integrity, showing that Zn is essential for maintaining the lining of the reproductive organs and may have a regulative role in the progress of capacitation and acrosome reaction. In contrast, Zn deficiency impedes spermatogenesis and is a reason for sperm abnormalities and has a negative effect on serum testosterone concentration. Based on these findings, Zn microelement is very essential for male fertility. It could be considered as a nutrient marker with many potentials in prevention, diagnosis, and treatment of male infertility.

The AhRR-c.565C>G transversion may increase total antioxidant capacity levels of the seminal plasma in infertile men.

The Aryl hydrocarbon receptor (AhR)-repressor (AhRR) is a regulator of the AhR pathway, which plays an important role in xenobiotic and reactive oxygen species (ROS) metabolism. Total antioxidant capacity (TAC) is a major factor in semen quality that protects sperm against ROS stress. Malondialdehyde (MDA) is the indicator of lipid peroxidation damage that is occurred due to ROSs. In this study, we determined and compared the MDA and TAC levels of infertile men's semen and blood plasma regarding genotype groups of AhRR-c.565C>G transversion. Semen and blood samples of 123 infertile males were collected from the Fatemeh Zahra IVF Centre, Babol, Iran. TAC and MDA levels of seminal and blood plasma were measured by TBARS and FRAP methods, respectively. Cases were genotyped by the PCR-RFLP method. The frequency of c.565C>G genotypes was determined as CC (34.14%), CG (55.28%) and GG (10.58%). Mean levels of TAC µm/L and MDA nmol/mL in semen plasma of CC, CG and GG groups were (1365.7, 1.28), (1542.8, 1.51) and (1860.2, 0.82), respectively. Also, mean levels of TAC µm/L and MDA nmol/mL in blood plasma samples in CC, CG and GG genotypes were (806.14, 1.168), (727.1, 1.006) and (635.7, 0.83), respectively. Comparison of marker levels between genotypes revealed that the TAC level of semen plasma in the GG genotype was significantly higher than its level in the CC group (p < 0.05). Our findings showed that in seminal plasma of infertile men with the GG genotype of AhRR-c.565C>G transversion, the level of total antioxidant capacity is significantly higher in comparison with the CC genotype. Then, the G allele of AhRR-c.565C>G transversion may have a role in the increase in antioxidant capacity of seminal plasma.