Search

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]

Several anticancer drugs are coadministered with ascorbate (ASCB) to complement their cytotoxic effects. However, it is not known if the treatment regimen prevents collateral oxidative damage to non-target sites. The current study evaluated the effect of ASCB cotreatment on the testes of young adult rats treated with an anticancer drug, busulfan (BUS). About 40 Wistar rats were arbitrarily assigned into four groups (N = 10), namely, control (<0.2% dimethyl sulfoxide vehicle), BUS (4 mg/kg b.w.; intraperitoneally for 4 days), BUS + ASCB (4 mg BUS/kg b.w. for 4 days + 100 mg ASCB/kg b.w.; intraperitoneally for 14 days and 7 days prior to start of BUS injection), and ASCB (100 mg/kg b.w.; intraperitoneally for 21 days). At the end of study, ASCB + BUS cotreatment reduced spermatogenesis score index, superoxide dismutase activity, total ASCB and decreased hydrogen peroxide level, and elevated catalase activity and nitrite concentration much more than treatment with BUS alone (P < 0.05). Other observations included elevated malondialdehyde level, DNA damage, and diminished glutathione concentration in the testes of BUS + ASCB animals. Interestingly, ASCB administration raised testicular ASCB concentration beyond the control values (P < 0.05) and the antioxidant status of the testes. Histological aberrations included many single layers of germ cells, shrinked tubules, and vacuolated structures in the epithelium of BUS + ASCB, similar to those of BUS-treated animals. In conclusion, BUS treatment deregulated the redox status of the testes and caused a dramatic consumption of ASCB which were enhanced by exogenous ASCB resulting to testicular damage. [ABSTRACT FROM AUTHOR]

The effect of fluted pumpkin seeds (FPS) consumption on the antioxidant status of the testes of aged Wistar rats was evaluated in this study. Sixty (50 aged, 6 months old, and 10 young, 2 months old) rats were divided into six groups of 10 per each group. Testosterone (15 mg kg-1 body weight, once weekly for 40 days) was injected intraperitoneally and used as positive control. FPS intake (50, 100, and 200 mg kg-1 body weight) or vehicle control (corn oil) were administered orally, twice weekly for 40 days and compared with the untreated aged and young control rats. Changes in antioxidant status in the testis of the aged rats was reflected as increased superoxide dismutase and catalase activities and glutathione and decreased lipid peroxidation levels which were attenuated more efficiently by the lowest dose FPS (50 mg kg-1 body weight). Additionally, nitrite concentration that was found to be diminished in the aged rats was raised to the young control values after intake of the FPS (50 mg kg-1 body weight). As expected, testosterone injection increased endogenous testosterone concentration and also remained higher in the untreated aged animals than in young control and treated aged rats. In conclusion, compromised antioxidant defense system of the testes that is associated with ageing could be reversed to the status of the young control by the intake of FPS. [ABSTRACT FROM AUTHOR]

Cadmium (Cd) is a toxic metal that damages several tissues of animals and humans including the testis. The ameliorative effects of quercetin (QUE), rutin (RUT), and gallic acid (GAL) at 20 mg kg-1 body weight alone or in combination against testicular injury induced by Cd (24 mg kg-1 body weight) in male Wistar rats were evaluated in this study. Forty-two (42) rats were randomly grouped into six (6) groups: (1) vehicle control group, (2) Cd group, (3) RUT+Cd group, (4) GAL+Cd group, (5) QUE+Cd group, and (6) RUT+GAL+QUE+Cd group. At the end of the oral gavage of the tested chemicals, the rats were sacrificed, blood samples were collected, and testes were harvested and processed for biochemical assays. Cd exposure damaged the testis (smaller epithelium thickness and spermatogenesis index and sloughing of the epithelium); increased lipid peroxidation, glutathione S-transferase activity, and DNA fragmentation; and diminished glutathione reductase activity and serum testosterone level 40 days posttreatment. Treatment with the phenolics separately or in combination attenuated the effect of Cd on serum testosterone, glutathione reductase and glutathione S-transferase activities, lipid peroxidation, and percent fragmented DNA. The increased nitric oxide concentration in the QUE+Cd group was attenuated to control values in the combined (RUT+GAL+QUE+Cd) exposure group. Coadministration of the phenolics appears to have more substantial protective effects than their single effects against Cd-induced testicular DNA damage, glutathione S-transferase activity, and the recovery of testosterone levels and spermatogenesis index. Overall, the tested phenolics can reduce testicular damage more efficiently in their combined form than individual administration. [ABSTRACT FROM AUTHOR]

The present study was designed to evaluate the protective effect of fluted pumpkin seeds (FPS) against caffeine (CAFF) induced testicular toxicity in rats. Thirty young healthy male Wistar rats (196 ± 12 g) were randomly organized into five sets of six animals per each group: control, caffeine (CAFF; 50 mg kg−1 bw) and FPS co‐treatment groups (CAFF + 50 mg FPS, CAFF + 100 mg FPS and CAFF + 200 mg FPS kg−1 bw). CAFF and FPS were administered daily and twice per week respectively by oral gavage for 40 days. CAFF treatment decreased testicular lactate dehydrogenase enzyme activity level, which was attenuated on co‐administration with FPS at 50 and 100 mg kg−1 bw. Furthermore, CAFF decreased seminiferous epithelia thickness and spermatogenesis score index and increased the number of tubules with abnormal histological features, which were attenuated on co‐administration with FPS at 50 mg kg−1 bw much more than at the higher doses (p < 0.05). CAFF did not affect malondialdehyde and glutathione concentrations and glutathione peroxidase (GSH‐Px) activity in the testes whereas FPS co‐treatment at the higher doses elevated glutathione level and GSH‐Px activity and did not affect spermatogenesis score index at the highest dose (200 mg kg−1 bw). Testicular malondialdehyde concentrations remained unaffected in all FPS co‐treatment groups. Overall, FPS is able to minimize the CAFF‐induced testicular injury at lower than at the higher tested doses. [ABSTRACT FROM AUTHOR]

This study evaluated the beneficial protective effect of cotreatment of curcumin (CUR) and quercetin (QUE) on atrazine (ATZ)‐induced testicular toxicity in rats. ATZ challenge diminished luteinizing hormone, follicular stimulating hormone, testosterone and myeloperoxidase enzyme activity, but these effects were attenuated on co‐treatment with CUR and QUE. Also, co‐treatment of CUR + QUE was better than separate administration of QUE at diminishing malondialdehyde and glutathione and improving tumour necrosis factor‐α concentration, germ cell numbers (spermatogonia, spermatocytes and round spermatids) and epididymal sperm quality. Histologically, smaller sized tubules with degenerated epithelia and few germ cells were seen in the seminiferous tubules of the ATZ group whereas CUR + QUE pretreatment improved the histo‐morphologic features of the tubules compared to the ATZ group and was also better than separate administration of QUE. We conclude that CUR can improve the protective effects of QUE against ATZ‐induced testicular injury by enhancing the levels of reproductive hormones, recovering testicular biochemical parameters and improving the histological features of the testes. [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]

This review attempts to collate existing data and provide the perspectives for future studies on the effects of plants on the male gonads. For many of these medicinal plants such as Lepidium meyenii, Rupus coreanus, Tribulus terrestres, Panax ginseng, Petasites japonicas, Apium graveolens, Eurycoma longifólia, Pedalium murex, Corchorus depressus, Mucuna pruriens, Astragalus membranaceus, Nigella sativa, Crataegus monogyna, Fagara tessmannii, Phaleria macrocarpa, Anacyclus pyrethrum, Cynomorium songaricum and Morinda officinalis, the mechanism of actions of their active principles and crude extracts has been shown in both laboratory animals, in vitro, and human studies, and includes their antioxidant, anti‐inflammatory, spermatogenesis‐inducing, aphrodisiac, smooth muscle relaxing and androgenic properties. Several active chemical leads including glucosinolates, anthocyanins, protodioscin, ginsenosides, sesquiterpenes, phyto‐oestrogens, quassinoids, diosgenin, thymoquinone, proanthocyanidins and bajijiasu isolated from these plants are known to have target effects on the testis, but efforts have been limited in their application at the clinical level. There still appear to be many more extracts of medicinal plants that have not been characterised to determine the phytochemicals unique to them that have target effects on the gonads. Further, collaborative efforts at isolating pro‐drug candidates from medicinal plants for studies at the molecular, cellular and clinical level towards elucidating their mechanisms of action on the testes are therefore warranted in the light of the current male fertility crisis. [ABSTRACT FROM AUTHOR]

ABSTRACT Quercetin ( QT), a dietary-derived flavonoid, is ubiquitous in fruits and vegetables and plays an important role in human health by virtue of its antioxidant function. The present study was designed to examine the effects of QT on oxidative damage that was induced by the herbicide, atrazine ( ATZ), in mixed cultures of Sertoli-germ cells. Results showed that treatment with QT increased cell viability and decreased catalase activity, malondialdehyde, and reactive oxygen species ( ROS) levels. QT treatment also increased the m RNA expression of glutathione peroxidase ( GSH- Px), glutathione reductase ( GR), glutathione-S-transferase, and superoxide dismutase-1 and could not reversed to the control levels ATZ-induced steady-state m RNA levels of these antioxidant genes as well as the level of glutathione and activities of GSH- Px and GR. QT has protective effect against ATZ-induced oxidative stress through a reduction in ROS levels and lipid peroxidation. © 2012 Wiley Periodicals, Inc. J Biochem Mol Toxicol 26:477-485, 2012; View this article online at wileyonlinelibrary.com. DOI 10:1002/jbt.21449 [ABSTRACT FROM AUTHOR]

Excessive and sustained increases in oxidative stress and apoptosis have been implicated in the pathogenesis of many diseases. In this study, we demonstrated that 4-hydroxynonenal (4-HNE), a product of lipid peroxidation in a range of concentration (0.1-50 μM) showed cytotoxic effects on SH-SY5Y cell culture at a concentration >5 μM at 4 hr of exposure. 4-HNE dose dependently decreased cell viability and significantly promoted reactive oxygen species formation and enhanced oxidative stress as reflected in the increased level of lipid peroxidation and catalase activity and decreased glutathione peroxidase activity as well as glutathione levels. 4-HNE-induced oxidative stress was associated with increased transcriptional and translational expressions of Bax and p53 in SH-SY5Y cells. Mitochondrial-mediated apoptosis was confirmed by increased expression and activity of caspase-3. Our data demonstrate that 4-HNE induces neuronal cell death through abnormal expression of apoptotic markers (p53, Bax and caspase-3). Oxidative stress may be involved in the initial priming of SH-SY5Y cells to 4-HNE-induced cytotoxicity in vitro. [ABSTRACT FROM AUTHOR]

This study evaluated the effect of methanol and aqueous ethanol root extracts (200 mg/kg body weight) of Anthocleista djalonensis on sex hormone concentrations and testicular marker enzymes of adult rats after 60 days of administration followed by 60 days of treatment withdrawal. The results showed no significant changes in testosterone and follicle‐stimulating hormone (FSH) levels during the 60 days of extract treatment. Interestingly, 60 days after treatment withdrawal, there was an increase in intratesticular and serum testosterone and serum FSH in the methanol but not aqueous ethanol extract post‐treatment groups. Intratesticular 3β‐hydroxysteroid dehydrogenase (3β‐HSD) activity remained unaffected while that of 17β‐HSD increased slightly during treatment of both extracts and the increase reached a statistical significance level (p < .05) during post‐treatment. Gamma‐glutamyltranspeptidase activity in the testis of the methanol but not aqueous ethanol extract‐treated animals remained high during post‐treatment compared to initial treatment values. Phytochemical analysis of the plant extracts showed that phenol and flavonoid constituents were higher in the methanol than the aqueous ethanol extract and has higher antioxidant activity. Altogether, post‐treatment effect of the extract on the testis was more effective than treatment‐related effect and the methanol extract appears to have better and consistent effects on the investigated parameters probably due to higher antioxidant activity conferred to it by its phenolic and flavonoid contents. [ABSTRACT FROM AUTHOR]