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Despite remarkable progress in the treatment of hepatitis C virus (HCV) infection, it remains a significant global health burden, necessitating the development of an effective prophylactic vaccine. This review paper presents the current landscape of HCV vaccine candidates and approaches, including more traditional, based on inactivated virus, and more modern, such as subunit protein, vectored, based on nucleic acids (DNA and mRNA) and virus‐like particles. The concept of the HCV vaccine is first put in the context of viral genetic diversity and adaptive responses to HCV infection, an understanding of which is crucial in guiding the development of an effective vaccine against such a complex virus. Because ethical dimensions are also significant in vaccine research, development, and potential deployment, we also address them in this paper. The road to a safe and effective vaccine to prevent HCV infection remains bumpy due to the genetic variation of HCV and its ability to evade immune responses. The progress in cell‐culture systems allowed for the production of an inactivated HCV vaccine candidate, which can induce cross‐neutralizing antibodies in vitro, but whether this could prevent infection in humans is unknown. Subunit protein vaccine candidates that entered clinical trials elicited HCV‐specific humoral and cellular responses, though it remains to be shown whether they translate into effective prevention of HCV infection or progression of infection to a chronic state. Such responses were also induced by a clinically tested vector‐based vaccine candidate, which decreased the viral HCV load but did not prevent chronic HCV infection. These disappointments were not readily predicted from preclinical animal studies. The vaccine platforms employing virus‐like particles, DNA, and mRNA provide opportunities for the HCV vaccine, but their potential in this context has yet to be shown. Ensuring the designed vaccine is based on conserved epitope(s) and elicits broadly neutralizing immune responses is also essential. Given failures in developing a prophylactic HCV vaccine, it is crucial to continue supporting national strategies, including funding for screening and treatment programs. However, these actions are likely insufficient to permanently control the HCV burden, encouraging further mobilization of significant resources for HCV vaccine research as a missing element in the elimination of viral hepatitis as a global public health. [ABSTRACT FROM AUTHOR]

In this study, we performed the stereological examination of rat testes and evaluated the protective effect of testosterone against atrazine (ATZ) toxicity in TM3 Leydig and TM4 Sertoli cells. Testosterone intake in rats increased the volumetric density of the seminiferous tubules; tubular diameter; germinal epithelial height; number of spermatogonia, primary and secondary spermatocytes, round spermatids, Sertoli cells, and Leydig cells; and Johnsen scores compared with the values after ATZ treatment (p < 0.05). Furthermore, testosterone increased the viability of TM3 cells and reduced reactive oxygen species (ROS) generation in TM4 cells compared to the ATZ‐treated group. In conclusion, exogenous testosterone intake maintains testicular morphometry and spermatogenesis in rats, and minimizes cell death and ROS generation in testicular cell lines exposed to ATZ. However, TM4 cells are more responsive to testosterone‐mediated regulation of ROS generation induced by ATZ than TM3 cells. [ABSTRACT FROM AUTHOR]

This study examined the effects of cadmium (Cd) on the testes of rats and the efficacy of fluted pumpkin seeds (FPS) supplementation. Twenty-four adult male rats (150–190 g) were allocated into four groups. I: control; corn oil (2 ml/kg); II: Cd (24 mg/kg); III: Cd (24 mg/kg) + FPS (25 mg/kg); IV: Cd (24 mg/kg) + FPS (250 mg/kg). After 44 days, the rats were killed and testes and serum were isolated for experimental analysis. Cd treatment significantly increased the concentrations of malondialdehyde, nitric oxide, and abnormal histological features (Sertoli cells-only tubules, atrophy, spermatogenesis arrest, and a reduced Johnsen's score). It also decreased the antioxidant defense of the testes and serum testosterone concentration. FPS extracts at both doses were able to recover spermatogenesis and steroidogenesis and inhibit oxidative stress caused by Cd. [ABSTRACT FROM AUTHOR]

Here, we studied the protective effect of gallic acid (GAL) as a potent anti-oxidant and anti-inflammatory agent against damage caused by busulfan (BUS) in the testes of adult rats. The adult Wistar rats were assigned as control, BUS: was intraperitoneally (i.p.) treated with busulfan (15 mg/kg, day 7 and 14), GAL + BUS: was co-treated with busulfan (i.p., 15 mg/kg, day 7 and 14) and orally treated (per os) with gallic acid (60 days, 20 mg/kg) and GAL: was treated with gallic acid (per os, 60 days, 20 mg/kg). The results showed that GAL co-treatment increased the numbers of spermatogonia (Type A and B), spermatocytes (primary and secondary) and round spermatids, along with the tubular diameter, epithelial height and gonado-somatic index. In addition, BUS-induced increase in 3β-hydroxysteroid dehydrogenase and γ-glutamyl transpeptidase activities were inhibited on GAL co-treatment. Similarly, BUS-induced decrease in gluthathione concentration, catalase and superoxide dismutase activities along with increase in myeloperoxidase activity and malondialdehyde concentration were significantly normalized to control values on GAL co-treatment. Busulfan-induced elimination of tubular germ cells was completely prevented by GAL. Overall, GAL may inhibit BUS-mediated spermatogenesis arrest via decreasing inflammatory-mediated oxidative stress in a rat experimental model. [ABSTRACT FROM AUTHOR]

Here, we studied the protective effect of rutin (RUT) against testicular damage caused by busulfan (BUS) in rats. Adult male Wistar rats were intraperitoneally injected with BUS (4 mg/kg body weight at day 7 and 14), and then treated with RUT (30 mg/kg body weight) by gavage thrice weekly for 60 days. The results showed that BUS-induced increase in 3β-hydroxysteroid dehydrogenase (3β-HSD) was significantly decreased by RUT, whereas 17β-HSD activity and plasma testosterone concentration remained unaffected (p > 0.05). It was also observed that RUT inhibited BUS-induced increase in nitrite concentrations and myeloperoxidase enzyme activities in the plasma and testes (p < 0.05). Similarly, BUS-induced decrease in glutathione and increase in malondialdehyde concentrations in the testes were significantly normalized to control values by RUT. Finally, RUT administration showed some tendency to improve the architecture of the seminiferous epithelium of the rat's testes after BUS treatment. Overall, RUT inhibited BUS-induced oxidative damage and inflammation in the testis of an experimental rat model. [ABSTRACT FROM AUTHOR]

There are few treatment options, including the use of natural phenolics-based combination therapy for mitigating male infertility conditions associated with chemotherapy. Busulfan is an anti-cancer drug that leads to testicular problems in humans. Here, we studied the effect of co-treatment of rutin and kolaviron against busulfan-induced testis damage. Young adult male Wistar rats were intraperitoneally injected busulfan (4 mg/kg b.w), and then orally administered rutin (30 mg/kg b.w), and kolaviron (50 mg/kg b.w) alone and combined for 60 days. Results revealed that rutin and kolaviron alone or in combination reversed busulfan-induced increase in oxidative stress along with sperm quality of treated animals. However, kolaviron and rutin separately improved the concentrations of MDA and GSH and sperm quality more than when they were combined. Similarly, rutin and kolaviron separately or in combination preserved spermatogenesis and relieved busulfan-induced increase in nitric oxide concentration, myeloperoxidase and 3β-hydroxysteroid dehydrogenase activities. Co-supplementation with kolaviron but not rutin nor when rutin was combined with kolaviron also improved the testicular level of tumor necrosis-alpha. Finally, the histological features in the testes caused by busulfan were reversed by rutin, whereas treatment with kolaviron alone or in combination with rutin partially protected the testis from busulfan-induced injury as demonstrated by the appearance of few germ cells, damaged tubules, loss of round spermatids and defoliation of the seminiferous epithelium. Thus, the combined treatment regimen of rutin and kolaviron sparingly prevented busulfan-induced testicular injuries in rats. Abbreviations: CAT: Catalase; GSH: Glutathione; 3β-HSD: 3β- hydroxysteroid Dehydrogenase; MDA: Malondialdehyde; TNF-α: Tumor necrosis-alpha; BUS: Busulfan; RUT: Rutin; KV: Kolaviron; TBARS: Thiobarbituric Acid Reactive Substances; MPO: Myeloperoxidase; ELISA: Enzyme-Linked Immunoassay; NAD: Nicotinamide Adenine Dinucleotide (oxidized); ROS: Reactive Oxygen Species. [ABSTRACT FROM AUTHOR]

The entire world has been suffering from the coronavirus disease 2019 (COVID‐19) pandemic since March 11, 2020. More than a year later, the COVID‐19 vaccination brought hope to control this viral pandemic. Here, we review the unknowns of the COVID‐19 vaccination, such as its longevity, asymptomatic spread, long‐term side effects, and its efficacy on immunocompromised patients. In addition, we discuss challenges associated with the COVID‐19 vaccination, such as the global access and distribution of vaccine doses, adherence to hygiene guidelines after vaccination, the emergence of novel severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) variants, and vaccine resistance. Despite all these challenges and the fact that the end of the COVID‐19 pandemic is still unclear, vaccines have brought great hope for the world, with several reports indicating a significant decline in the risk of COVID19‐related infection and hospitalizations. Highlights: 1.Vaccination plays a pivotal role in reducing the death toll of the COVID‐19 infection.2.The immunity provided by vaccines is still disputable leading to some challenges like the asymptomatic spread; therefore, staying strict to hygiene guidelines is necessary.3.Hence, COVID‐19 vaccines' related long‐term side effects are still unknown; cautions should be taken when injected to various individuals of the community.4.COVID‐19 vaccines' effectiveness are strongly related to their effect on emergent COVID‐19 variants, but until now approved vaccines can still show some protective effects against new variants. [ABSTRACT FROM AUTHOR]

The present study evaluated the protective effect of fluted pumpkin seeds (FPS) on atrazine (ATZ)-induced testicular damage. Twenty adult male Wistar rats were divided into four groups of five animals each. The control animals (Group A) received corn oil (2 mL/kg body weight), Group B animals received 50 mg ATZ/kg body weight by gavage, while Groups C and D received 50 mg ATZ/kg body weight once a week in addition to the gavage of 25 mg FPS/kg body weight and 50 mg FPS/kg body weight respectively for 60 days. The results showed that testicular myeloperoxidase activity and nitrite concentration were decreased in all groups compared to the control value. The increase in malondialdehyde and decrease in glutathione concentrations in group B were abrogated in group C (p < 0.05) but not in group D animals. The increase in γ-glutamyl transpeptidase and decrease in lactate dehydrogenase enzyme activities in the group B animals were also normalized to control values in group C but not in group D animals. Interestingly, the testis of the group D animals showed massive depletion of germ cells and the diameter of the seminiferous tubules of these animals were decreased compared to all other groups. However, the number of motile sperms, abnormal sperms and sperm count in Group D animals were similar to the ATZ-treated animals and lower than control values. In conclusion, FPS protected against ATZ-induced testicular damage but can also harm the testis at a higher dose. [ABSTRACT FROM AUTHOR]

The antioxidant protective effects of gallic acid (GAL) and quercetin (QUE) against oxidative stress induced by di-butyl phthalate (DnBP) in the liver and testis of rats were evaluated in this study. Adult albino Wistar rats (180–225 g) were treated with QUE or GAL (50 mg/kg) alone or in combination with DnBP (1 mL/kg) for 15 days. After treatment, tissue samples were taken for determination of glutathione and malondialdehyde levels, and superoxide dismutase and catalase activities. Serial sections of the testis and liver were stained with haematoxylin and eosin for microscopy and seminiferous tubular morphometry. As expected, DnBP induced oxidative stress was evident by increased malondialdehyde level in both organs. Co-treatment with GAL or QUE reversed the malondialdehyde by 45.42, 37.44 and 37.57%, 23.32% and catalase by 52.21, 70.15 and 85%, 38.14% in the testis and liver respectively whereas superoxide dismutase activity and glutathione level were differently modulated parallel to histopathological improvement in both tissues. The seminiferous tubular diameter, epithelial height, epithelial germ cell count and tubular length were significantly decreased by 11.09, 51.91, 40.65 and 11.10% respectively versus control values after DnBP treatments and were attenuated on co-treatment with GAL or QUE. Co-treatment with GAL afforded better protective effects in both tissues but QUE treatment alone appeared more effective than GAL on the investigated morphometric data. It seems likely that GAL or QUE prevented the tissue damage but the antioxidant profiles of the liver and testis are different in response to the oxidative stress. [ABSTRACT FROM AUTHOR]