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Semen cryopreservation is a crucial technique for preserving male fertility, playing a vital role in assisted reproductive procedures by storing frozen semen samples for artificial insemination (AI) and intra-cytoplasmic sperm injection (ICSI) to enhance reproductive success rates. This study aims to identify the most effective cryopreservation methods and assess their impact on semen quality, particularly sperm DNA fragmentation. A total of 30 semen samples were categorized into fertile and infertile groups. DNA fragmentation analysis was conducted using the Sperm Chromatin Structure Assay (SCSA). Each sample was divided into three portions and frozen using different cryoprotectants: (egg-yolk + glycerol), (sucrose + glycerol), and (glycerol alone). After one month of storage, the samples were analyzed to determine the most effective medium. The findings revealed a decline in sperm motility post-freezing compared to fresh samples, along with a slight increase in morphological abnormalities. Additionally, there was a rise in sperm DNA fragmentation and an increase in apoptotic marker (Caspase-3) levels after the freezing process. The study concluded that cryopreservation and thawing caused some degree of sperm cell damage, with infertile samples being more adversely affected than fertile ones.

Exposure to light at night, pineal gland impairment, and the environmental pollutant trichloroethylene (TCE) have serious implications for health and contribute to illness, including liver cancer. The adverse effect of the association of continuous exposure to light with decreased melatonin levels and TCE-induced toxicity is not disclosed in target organs. This work explored the role of light and pineal impairment in increasing susceptibility to liver toxicity and cancer upon exposure to TCE. Male albino mice were divided into groups as follows: control group (12-h light/12-h dark cycle), constant light (24-h light), pinealectomized (Pnx) mice, sham surgically treated group, TCE-treated groups subjected to two doses (500 and 1000 mg/kg) at two different light regimens, and combination of Pnx and TCE-treated mice kept at a 12-h light/12-h dark cycle. Melatonin levels were significantly decreased in both Pnx mice and TCE-treated animals at both light regimens. Aspartate transaminase, alanine aminotransferase, activities, and serum bilirubin levels were significantly elevated, whereas albumin levels were markedly decreased in Pnx mice, TCE-treated mice, and the combination group. Histopathological investigations reflected changes in liver function parameters indicating liver injury and induction of cancer. These effects were accompanied by significant increase of the liver cancer biomarker alpha-fetoprotein and the expression of the metastatic markers CD44, TGFβ-1, and VEGF, along with increased oxidative stress indicators and inflammatory cytokines (IL-6, IL-1β, and TNF-α) in both Pnx and TCE-treated mice and the combination group at both light regimens. Taken together, our findings indicated that low melatonin levels, exposure to constant light, and the combination of both factors increases susceptibility to the toxic and carcinogenic effects of TCE on the liver.

While the precise mechanisms of melanoma development are unknown, recent in vivo studies have revealed that the p16Ink4a/Rb pathway is disrupted in melanomagenesis. Here, we characterize the role of p16/Rb in coordinating the early events in UVB-irradiated skin. Foreskins and melanoma cell cultures were irradiated with low and high acute UVB doses and examined for cell-cycle- and apoptosis-associated genes. In melanoma cells, low UVB dose upregulated p16, p53, and p21 expression levels in Malme-3M, and high UVB dose accentuated the expression of p53 and p21Cip1/Waf1, in particular; however, in SkMel-28 cells only p16 expression was upregulated in response to UV irradiation. In HaCaT cells, high UVB dose caused dramatic increase in p53 expression followed by upregulation of p21Cip1/Waf1 and Bax, and downregulation of Bcl-2 leading to apoptosis. In HaCaT cells, reinstatement of p16 pathway restored cell-cycle arrest in response to low dose. Foreskin organ culture experiments confirmed our in vitro cell results. These data indicate that the p53 and p16 pathways respond independently to UVB insult. The p16 pathway is favored at low doses and results in cell-cycle arrest; the p53 pathway is more responsive to higher doses and induces apoptosis depending on p53 mutation status.

Purpose: This study evaluated the protective effects of protodioscin against doxorubicin (DOX)-induced ovarian injury by examining its potential to modulate hormonal alterations and apoptosis-related pathways in a rat model. Methods: Forty female Wistar rats were randomized into four groups: control, protodioscin (10 mg/kg orally for 14 days), DOX (10 mg/kg intraperitoneally on Day 7), and DOX plus protodioscin. Serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), anti-Müllerian hormone (AMH), and 17β-estradiol (E2) were quantified using enzyme-linked immunosorbent assay. Ovarian histopathology and immunohistochemistry were performed to evaluate tissue integrity and expression of p53, CDK4, and Survivin. Gene expression of Bax and Bcl-2 was assessed using semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). Results: DOX administration significantly reduced ovarian weight by 38.5% and uterine weight by 22.6% (P < 0.01) compared with controls, accompanied by marked hormonal alterations, including increased FSH and decreased LH, AMH, and E2 levels. DOX also increased p53 and Bax expression and decreased Bcl-2 expression, resulting in an elevated Bax/Bcl-2 ratio. Co-treatment with protodioscin significantly attenuated these changes, partially restoring hormonal levels and modulating apoptosis-related markers. Protodioscin reduced p53 and Bax expression while increasing Bcl-2, CDK4, and Survivin levels, leading to a marked reduction in the Bax/Bcl-2 ratio (P < 0.05). Conclusion: Protodioscin exerts a protective effect against DOX-induced ovarian injury, likely through modulation of hormonal disturbances and apoptosis-related pathways. However, these findings should be interpreted with caution due to the absence of estrous cycle synchronization and the use of an acute DOX model.

While the precise mechanisms of melanoma development are unknown, recent in vivo studies have revealed that the p16 super(Ink4a)/Rb pathway is disrupted in melanomagenesis. Here, we characterize the role of p16/Rb in coordinating the early events in UVB-irradiated skin. Foreskins and melanoma cell cultures were irradiated with low and high acute UVB doses and examined for cell-cycle- and apoptosis-associated genes. In melanoma cells, low UVB dose upregulated p16, p53, and p21 expression levels in Malme-3M, and high UVB dose accentuated the expression of p53 and p21 super(Cip1/Waf1), in particular; however, in SkMel-28 cells only p16 expression was upregulated in response to UV irradiation. In HaCaT cells, high UVB dose caused dramatic increase in p53 expression followed by upregulation of p21 super(Cip1/Waf1) and Bax, and downregulation of Bcl-2 leading to apoptosis. In HaCaT cells, reinstatement of p16 pathway restored cell-cycle arrest in response to low dose. Foreskin organ culture experiments confirmed our in vitro cell results. These data indicate that the p53 and p16 pathways respond independently to UVB insult. The p16 pathway is favored at low doses and results in cell-cycle arrest; the p53 pathway is more responsive to higher doses and induces apoptosis depending on p53 mutation status.Journal of Investigative Dermatology (2009) 129, 175-183; doi:10.1038/jid.2008.208; published online 21 August 2008

Metformin is a widely used antidiabetic biguanide. Retrospective data demonstrated the association of metformin use with survival benefit in multiple tumor types. Interest in repurposing metformin to treat cancer has not been translated into encouraging clinical benefit. In animal models, metformin activated cytotoxic T cells and exerted an immune-mediated anticancer effect. The current research was conducted to investigate the possible therapeutic benefit of metformin in combination with metronomic cyclophosphamide in an experimental cancer model.Ehrlich ascites carcinoma was injected into the subcutaneous tissue to induce solid tumors in syngeneic mice. Exponential solid tumor growth ensued and was effectively arrested with the administration of a cytotoxic dose of parenteral cyclophosphamide. Alternatively, oral metformin and continuous, low-dose cyclophosphamide significantly inhibited tumor growth relative to untreated mice. The drug combination was well tolerated. Histopathological examination of the tumor showed an increased number of tumor-infiltrating lymphocytes and enhanced expression of granzyme B by this drug combination.The current data suggests a potential role of metformin and metronomic chemotherapy that warrants further investigation.