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The role of reactive oxygen species in the development of cancer has become well recognized in recent years; however, evidence for a link between oxidative stress and cancer risk has not been fully explored. One of the major cancers whose number of cases has increased significantly in recent years is colon and rectal cancer, which has the second highest mortality rate in Libya. Forty subjects were divided into three groups (20 tumors from colorectal cancer patients, adjacent surrounding tumor tissues, and 20 adjacent normal tissues). Evaluation of oxidative stress indices in the samples was performed by analyzing enzymatic and non-enzymatic parameters including the activity of glutathione peroxidase and catalase as antioxidant enzymes, reduced glutathione as an antioxidant, malondialdehyde MDA levels as an oxidative damage product, nitritc oxide content NO as an inflammatory marker, and total thiols as a measure of redox status. MDA and NO levels were significantly higher in tumor tissues than in adjacent healthy tissue. Also, the surrounding tumor tissue exhibited higher MDA and NO levels compared with control tissues. The oxidant and antioxidant levels in the tumor was significantly lower than those in the surrounding tumor tissue and control healthy tissue. The results suggest that oxidant and antioxidant parameters can be used as indicators of an imbalance in humans, and as this imbalance increases, the human body may be vulnerable to developing cancer. [ABSTRACT FROM AUTHOR]

Background: During early life, exposure to environmental toxicants, including endocrine disruptor bisphenol A (BPA), can be detrimental to the immune system. To our knowledge, a few researches have looked at the effects of developing BPA exposures on the spleen. Aim: The murine model was developed to investigate the underlying molecular mechanisms and mode of BPA actions on the spleen subsequent to prolonged early-life exposure to BPA. Methods: Immature (3-week-old) male and female Swiss Albino mice were intraperitoneally injected with 50 µg/kg BPA in corn oil or corn oil alone for 6 weeks. Mouse spleens were harvested and examined histologically at 10 weeks old (adulthood). Results: We observed neurobehavioral impairments and a significant increase in peripheral monocyte and lymphocyte counts in mice (males and females). Moreover, several spleen abnormalities in both male and female mice were observed in adulthood. BPA-treated mice's histopathological results revealed toxicity in the form of significantly active germinal centers of the white pulp and a few apoptotic cells. There was also a notable invasion of the red pulp by eosinophils and lymphocytes that were significantly higher than normal. Agarose gel electrophoresis provided further evidence of internucleosomal DNA fragmentation and apoptosis in the splenic tissues of BPA-treated mice compared to controls. In addition, there were increased levels of the lipid peroxidation malondialdehyde end-product, a marker of oxidative lipid damage, in the spleens of BPA-treated mice compared to controls. Conclusion: Our study provides evidence that oxidative stress injury induced by early-life exposures to BPA could contribute to a range of splenic tissue damages during adulthood. [ABSTRACT FROM AUTHOR]

Background: During early development, environmental compounds can induce adult onset diseases and disrupt the circulating vitamin D (VitD) levels. Aim: This study aimed to examine the protective role of VitD against the adverse effects of BPA on male and female mice. Methods: A total of 60 male and female Swiss Albino mice (3 weeks old) were randomly divided into 5 groups; each consisted of 12 mice (6 males and 6 females) and was treated as follows: Group I received no treatment (sham control); Group II, sterile corn oil only (vehicle control); Group III, BPA (400 μg/kg); Group IV, VitD (2,195 IU/kg); and Group V, BPA + VitD. At 10.5 weeks, the animals were sacrificed to conduct histological examinations. Results: BPA-exposed mice were found to have neurobehavioral abnormalities, heart, kidney, and lung diseases with increased apoptotic indices in both sexes. On the other hand, the treatment of BPA mice with VitD altered this scenario with modulated motor activity, enhanced body and organ weights, and preserved the heart, kidney, and lung architecture, alongside a decreased percent apoptotic index. Conclusion: Our findings illustrate that VitD protects mice against BPA-induced heart, kidney, and lung abnormalities. [ABSTRACT FROM AUTHOR]

Background: During development, oligodendrocyte (OL) lineage cells are susceptible to injury, leading to life-long clinical neurodevelopmental deficits, which lack effective treatments. Drugs targeting epigenetic modifications that inhibit histone deacetylases (HDACs) protect from many clinical neurodegenerative disorders. Aim: This study aimed to investigate the therapeutic potential of histone deacetylase 2/3 (HDAC2/3) inhibitor MI192 on white matter (WM) pathology in a model of neonatal rat brain injury. Methods: Wistar rats (8.5-day-old, n = 32) were used to generate brain tissues. The tissues were cultured and then randomly divided into four groups and treated as following: group I (sham); the tissues were cultured under normoxia, group II (vehicle); DMSO only, group III (injury, INJ); the tissues were exposed to 20 minutes oxygen-glucose deprivation (OGD) insult, and group IV (INJ + MI192); the tissues were subjected to the OGD insult and then treated with the MI192 inhibitor. On culture day 10, the tissues were fixed for biochemical and histological examinations. Results: The results showed that inhibition of HDAC2/3 activity alleviated WM pathology. Specifically, MI192 treatment significantly reduced cell death, minimized apoptosis, and mitigates the loss of the MBP+ OLs and their precursors (NG2 + OPCs). Additionally, MI192 decreased the density of reactive microglia (OX-42+). These findings demonstrate that the inhibition of HDAC2/3 activity post-insult alleviates WM pathology through mechanism(s) including preserving OL lineage cells and suppressing microglial activation. Conclusion: The findings of this study suggest that HDAC2/3 inhibition is a rational strategy to preserve WM or reverse its pathology upon newborn brain injury. [ABSTRACT FROM AUTHOR]

A growing body of studies suggests that Ca 2+ signaling controls a variety of biological processes in brain elements. Activation of L-type voltage-operated Ca 2+ channels (VOCCs) plays a role in the development of oligodendrocyte (OL) lineage loss, and indicates that the blocking of these channels may be an effective way to inhibit OL lineage cell loss. For this study, 10.5-day-old male Sprague-Dawley rats were used to generate cerebellar tissue slices. The slice tissues were cultured and randomly allocated to one of four groups (six each) and treated as follows: Group I, (sham control); Group II, 0.1% dimethyl sulfoxide (DMSO) only (vehicle control); Group III, injury (INJ); Group IV, (INJ and treatment with NIF). The injury was simulated by exposing the slice tissues to 20 min of oxygen-glucose deprivation (OGD). At 3 days post-treatment, the survival, apoptosis, and proliferation of the OL lineages were measured and compared. Results: In the INJ group, there was a decrease in mature myelin basic protein+ OLs (MBP+ OLs) and their precursors, NG2 + OPCs (Nerve-glia antigen 2+ oligodendrocyte precursor cell), compared with controls. A significant elevation was observed in the NG2 + OPCs and apoptotic MBP + OLs as confirmed by a TUNEL assay. However, the cell proliferation rate was decreased in NG2 + OPCs. NIF increased OL survival as measured by apoptosis rate in both OL lineages and preserved the rate of proliferation in the NG2 + OPCs. Conclusions: Activation of L-type VOCCs may contribute to OL pathology in association with reduced mitosis of OPCs following brain injury as a strategy to treat demyelinating diseases.

Background & Aim: Significant evidence indicates that endocrine disrupted bisphenol A (BPA) seriously endangers human health. In males, BPA affects testis architecture and sperm quality, and ultimately reduces fertility. This study explored the therapeutic potential of Nigella sativa (NS) seed extract on testis and sperm abnormalities in BPA-exposed mice and characterized the underlying mechanism., Methods: Forty male Swiss albino mice (5.5 weeks old, N = 8 per group) were randomly divided into five groups: Group I, normal control, Group II, vehicle control (sterile corn oil); Group III, NS-exposed (oral 200 mg/kg); Group IV, BPA-exposed (oral 400 μg/kg body weight); Group V, BPA + NS-exposed mice. Animals were treated for 6 weeks and sacrificed for biochemical and histological examination., Results: The results indicated that BPA exposure results in significant testis and sperm abnormalities. Specifically, BPA promoted a marked reduction in the body and testis compared with the control group. Histopathological findings showed that BPA caused a widespread degeneration of spermatogenic cells of the seminiferous epithelium, decreased sperm counts and motility, and augmented sperm abnormalities, and whereas little alteration to sperm DNA was observed. In addition, BPA increased the levels of the lipid peroxidation marker, malondialdehyde (MDA), and reduced the levels of the antioxidant marker, reducing glutathione (GSH). Treatment with NS oil extract during BPA exposure significantly alleviated testis and sperm abnormalities, reduced MDA levels, and enhanced GSH levels., Conclusion: The results demonstrate that NS oil protects mice against BPA-induced sperm and testis abnormalities, likely by suppressing levels of the oxidative stress marker, MDA, and enhancing the levels of the antioxidant marker, GSH., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Cellular elements of maturing brain are vulnerable to insults, which lead to neurodevelopmental defects. There are no established treatments at present. Here we examined the efficacy of selective adenosine A 2A receptor inhibitor SCH58261 to combat brain injury, particularly oligodendrocyte (OL) lineage cells, in young rats. Wistar rats (n = 24, 6.5 days old) were randomly divided into equal groups of four. The sham (SHAM) group received no treatment, the vehicle (VEHICLE) group received 0.1% dimethylsufoxide, the injury (INJ) group was exposed to oxygen-glucose deprivation insult, and the injury+SCH58261 (INJ+SCH58261) group was exposed to the insult and received 1 μM SCH58261. Immunocytochemical experiments revealed that there was a significant reduction in the populations of mature OL (MBP + OLs) and immature OL precursors (NG2 + OPCs) in the INJ group compared to SHAM group. Furthermore, there was also a significant increase in the percent of apoptotic MBP + OL and NG2 + OPC populations as evidenced by TUNEL assay. In addition, there was a significant reduction in the proliferation rate among NG2 + OPCs, which was confirmed by BrdU immunostaining. On the other hand, treatment with SCH58261 significantly enhanced survival, evidenced by the reduction in apoptotic indices for both cell types, and it is preserved the NG2 + OPC proliferation. Activation of adenosine A 2A receptors may contribute to OL lineage cell loss in association with decreased mitotic behavior of OPCs in neonatal brains upon injury. Future investigations assessing ability of SCH58261 to regenerate myelin will provide insights into its wider clinical relevance., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 The Author(s).)