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This study evaluated the possible neuroprotective effect of Allium atroviolaceum extract (AaE)-synthesized selenium nanoparticles (SeNPs) on aluminum (Al)-induced neurotoxicity in mice, explaining the likely mechanisms. Mice were divided into five groups: G1, control; G2, AaE group that received AaE (200 mg/kg) for 4 weeks; and groups 3, 4, and 5 received AlCl3 (100 mg/kg) for 3 weeks. After that, G4 received AaE (200 mg/kg), and G5 received SeNPs-AaE (0.5 mg/kg) for another 1 week. Exposure to AlCl3 boosted oxidative damage in brain tissue as evidenced by a reduction in glutathione concentrations and other antioxidant enzymes along with increased lipid peroxidation and nitric oxide levels. There was also a rise in the concentrations of interleukin-1β, TNF-α, and cyclooxygenase-II activities. AlCl3-treated mice showed reduced brain-derived neurotrophic factor (BDNF) and dopamine levels, increased acetylcholinesterase (AChE) activity, and reduced Bcl-2, and Bax, and caspase-3 activities. Treatment with SeNPs-AaE significantly reduced markers of oxidative stress, inflammation, and apoptosis. In addition, in SeNPs-AaE-treated rats, levels of BDNF and dopamine were significantly increased along with a reduction in AChE as compared with the AlCl3 group. Therefore, our results indicate that SeNPs-AaE has a potential neuroprotective effect against Al-mediated neurotoxic effects because of its powerful antioxidant, anti-inflammatory, anti-apoptotic, and neuromodulatory activities.

In this study, the neuroprotective potential of either Pergularia tomentosa leaf methanolic extract (PtE) alone or in combination with selenium nanoparticles (SeNPs-PtE) was investigated against lead acetate (PbAc)-induced neurotoxicity. Experimental rats were pretreated with PtE (100 mg/kg) or SeNPs-PtE (0.5 mg/kg) and injected intraperitoneally with PbAc (20 mg/kg) for 2 weeks. Notably, SeNPs-PtE decreased brain Pb accumulation and enhanced the level of dopamine and the activity of AChE compared to the control rats. In addition, elevated neural levels of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glutathione along with decreased lipid peroxidation levels were noticed in pretreated groups with SeNPs-PtE. Moreover, SeNPs-PtE significantly suppressed neural inflammation, as indicated by lower levels of interleukin-1 beta, interleukin-6, tumor necrosis factor-alpha, nuclear factor-kappa B p65, and nitric oxide in the examined brain tissue. The molecular results also unveiled significant down-regulation in iNOS gene expression in the brains of SeNPs-PtE-treated rats. In addition, SeNPs-PtE administration counteracted the neural loss by increasing B-cell lymphoma 2 (Bcl-2) and brain-derived neurotrophic factor levels as well as decreasing BCL2-associated X protein and caspase-3 levels. To sum up, our data suggest that P. tomentosa extract alone or in combination with SeNPs has great potential in reversing the neural tissue impairment induced by PbAc via its antioxidant, anti-inflammatory, and anti-apoptotic activities. This study might have therapeutic implications in preventing and treating several lead-induced neurological disorders.

Vincamine, a monoterpenoid indole alkaloid with vasodilatory properties, is extracted from the leaves of Vinca minor. The present study aimed to determine the potential anticancer effects of vincamine loaded in silver nanoparticles (VCN-AgNPs) in mice with Ehrlich solid carcinoma (ESC). After tumor transplantation, the mice were divided into five groups: ESC, ESC+Cisplatin (CPN; 5 mg/kg), ESC+VCN (40 mg/kg), ESC+AgNPs (6 mg/kg), and ESC+VCN-AgNPs (20 mg/kg). The administration of VCN-AgNPs to ESC-bearing mice improved their survival rate and reduced their body weight, tumor size, and tumor weight compared to the ESC group. Furthermore, VCN-AgNPs intensified oxidative stress in tumor tissues, as evidenced by elevated levels of lipid peroxidation (LPO) and nitric oxide (NO), along with a reduction in the levels of the antioxidants investigated (GSH, GPx, GR, SOD, CAT, and TAC). Furthermore, VCN-AgNPs increased the apoptotic proteins Bax and caspase-3, decreased the anti-apoptotic protein (Bcl-2), increased the inflammatory markers TNF-α and IL-1β, and inhibited angiogenesis by lowering VEGF levels in tumor tissues, all of which led to apoptosis. Furthermore, histopathological studies showed that VCN-AgNPs suppressed the progression of Ehrlich carcinoma and induced the formation of clusters of necrotic and fragmented tumor cells. VCN-AgNPs possess cytotoxic and genotoxic effects against ESC because of their pro-oxidant, pro-apoptotic, pro-inflammatory, and antiangiogenic effects. Additionally, the combination of VCN-AgNPs was more effective and safer than chemically synthesized AgNPs, as indicated by an increase in the lifespan of animals and the total tumor inhibition index. [ABSTRACT FROM AUTHOR]

Purpose: Resistance to Trastuzumab is a significant challenge in the management of HER2-positive Metastatic Breast cancer (HER2-MBC), and a better understanding of the molecular causes of resistance is required to develop more effective treatment plans. While elevated plasma levels of miR-200 and FOXP3 have been linked to breast cancer progression and treatment response, no clinical studies have confirmed these results. Methods: The study involved 40 patients with HER2-positive metastatic breast cancer (HER2-MBC). The expression levels of miR-200c-3p and the FOXP3 gene were assessed in plasma samples at two time points: baseline (BL) and after the consent completion of one cycle of Trastuzumab, utilizing quantitative polymerase chain reaction (qPCR). Clinical response to Trastuzumab was evaluated 12 months post-therapy and correlated with the time to progression (TTP) through Kaplan-Meier analysis. Results: Low plasma expression level of miR-200c-3p was detected before therapy in HER2-MBC, compared to healthy controls, and decreased dramatically in the follow-up sample at disease progression, while increased after one cycle of Trastuzumab therapy in patients who were sensitive to Trastuzumab. At baseline, a low expression level of miR-200c was significantly associated with overexpression of FOXP3, poor prognosis, and shorter time to progression. Conclusions: The findings suggest that miR-200c-3p may be a promising biomarker for predicting the response to Trastuzumab in HER2-MBC patients. [ABSTRACT FROM AUTHOR]

The disadvantages and side effects of currently available breast cancer (BC) therapies have compelled researchers to seek new therapeutic strategies. This study was designed to investigate the effect of selenium nanoparticles biosynthesized with carvacrol (SeNPs-CV) on breast cancer (MCF-7) cell lines and to explore possible underlying pathways. Flow cytometry, MTT assays, and various biochemical techniques were used to evaluate the anti-proliferative effects of SeNPs-CV on MCF-7 cells. Cytotoxicity assays showed that treatment with SeNPs-CV could effectively reduce MCF-7 cell proliferation and viability in a dose-dependent manner. However, SeNPs-CV had no cytotoxic effect against Vero cells. Furthermore, SeNPs-CV showed better anticancer activity than metal nanoparticles of selenium evidenced by the lower IC50 obtained in MCF-7 cells (8.3 µg/mL versus 41.6 µg/mL, respectively). Treatment with SeNPs-CV directly targeted Bcl-2, Bax, and caspase-3, leading to the mitochondrial leakage of cytochrome C and subsequent activation of the apoptotic cascade in MCF-7 cells. In addition, MCF-7 cells treated with SeNPs-CV exhibited elevated levels of oxidative stress, as indicated by noticeable rises in 8-OHDG, ROS, NO, and LPO, paralleled by significant exhaustion in GSH levels and antioxidant enzymes activity. In addition, the administration of SeNPs-CV induced the inflammatory mediator IL-1β and downregulated the expression of cell-proliferating nuclear antigen (PCNA) in MCF-7 cells, which plays a critical role in apoptosis. Therefore, the ability of SeNPs-CV to fight BC may be due to its ability to induce oxidative stress, inflammation, and apoptosis in tumor cells. These findings demonstrate the therapeutic potential of Se nanoparticles conjugated with CV, which may provide a novel approach for combination chemotherapy in BC. [ABSTRACT FROM AUTHOR]

Snakebite is a serious and important problem in tropical and subtropical countries including Egypt. The venom of Egyptian cobra (Naja haje; L.) is complex, and it has been considered as a good source of short neurotoxins and several cytotoxins. In this study, oxidative stress inductions as well as apoptotic effects of the Egyptian cobra crude venom al a dose of 0.025mg/kg (intraperitoneal injection; i.p.) has been investigated in kidney of rats after 4 h. Twelve rats divided into 2 groups, Group I served as control group, Group II received i.p. injection of 0.025mg/kg of crude venom. The venom enhanced lipid peroxidation and nitric oxide productions in the kidney with concomitant reduction in glutathione content and superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glutathione-S-transferase activities were inhibited. Moreover, the venom induced a renal injury' as indicated by histopathological changes in the kidney tissue with an elevation in serum creatinine and urea. In addition, the renal ultrastructural changes were in the form of blebbing of visceral epithelial cells, and foot process disorganization. Also, the glomerular capillaries lined by hypertrophied endothelial cells. These findings were associated with the pro-apoptotic action in the kidney. The results suggest that Egyptian cobra venom stimulates oxidative stress to induce apoptosis in renal tissue through inhibition of mitochondrial respiration in male rats. [ABSTRACT FROM AUTHOR]

We investigated the effects of methanolic leaves extract of Azadirachta indica (MLEN, 500mg/kg bwt) on cisplatin-(CP-) induced nephrotoxicity and oxidative stress in rats. CP (5 mg/kg bwt) was injected intraperitoneally and MLEN was given by gastric gavage for 5 days before or after CP injection. After 5 days of CP injection, CP-induced injury of the renal tissue was evidenced (i) as histopathological damage of the renal tissue, (ii) as increases in serum uric acid, urea, and creatinine, (iii) as increases in malondialdehyde (MDA) and nitric oxide (NO), (iv) as decreases in the level of glutathione and activities of superoxide dismutase, catalase, glutathione reductase, glutathione-S-transferase, and glutathione peroxidase, and (v) as increase in the expression of nuclear factor kappa B and apoptosis in kidney tissues. However, the oral administration of MLEN to CP-intoxicated rats for 5 days brought back MDA, NO production, and enzymatic and nonenzymatic antioxidants to near normalcy. Moreover, the histological observations evidenced that neem extract effectively rescues the kidney from CP-mediated oxidative damage. Furthermore, PCR results for caspase-3 and caspase-9 and Bax genes showed downregulation in MLEN treated groups. Therefore, Azadirachta indica can be considered a potential candidate for protection of nephrotoxicity induced by cisplatin. [ABSTRACT FROM AUTHOR]