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Long-term exposure to environmental neurotoxic metals is implicated in the induction of dementia and cognitive decline. The present study aims to illustrate the therapeutic role of ipriflavone as a synthetic isoflavone against environmental metal–induced cognitive impairment in rats. Dementia was induced by a mixture of aluminum, cadmium, and fluoride for 90 days followed by ipriflavone for a further 30 days. Metal-treated animals exhibited abnormal behaviors in the Morris water maze task. Neuropathological biomarkers including oxidative stress (TBARS, NO, SOD, GPX, GST, and GSH), inflammation (TNF- α, IL-6, and IL-1β), neurotransmission (AChE and MAO), and insulin resistance (insulin, insulin receptor, and insulin-degrading enzyme) were altered, which consequently elevated the level of amyloid-β42 and tau protein in the hippocampus tissues inducing neuronal injury. Ipriflavone significantly (P < 0.05) ameliorated the neurobehavioral abnormalities and the cognitive dysfunction biomarkers via antioxidant/anti-inflammatory mechanism. Moreover, ipriflavone downregulated the mRNA expression level of amyloid precursor protein and tau protein, preventing amyloid plaques and neurofibrillary tangle aggregation at P < 0.05. A molecular docking study revealed that ipriflavone has a potent binding affinity towards AChE more than donepezil and acts as a strong AChE inhibitor. Our data concluded that the therapeutic potential of ipriflavone against dementia could provide a new strategy in AD treatment.

Background: Nonalcoholic steatohepatitis (NASH) is associated with activation of liver fibrogenesis and predisposes to cirrhosis and associated morbi-mortality. A high fat high cholesterol diet (HFD) was provided to female albino rats to establish a NASH model. It is well known that the offspring of obese mothers have an increased risk of obesity and diabetes. The present study aimed at evaluating the ameliorative effects of ipriflavone (IP) as a natural food supplement on lipid metabolism, improving insulin sensitivity, reducing oxidative stress and inflammation, modifying metabolic risk factors and/or reduce brain damage, in both neonates and their dams. Materials and Methods: The present aim was achieved by evaluating the oxidative stress and antioxidant defense system biomarkers, as thiobarbituric acid reactive substances (TBARS) and reduced glutathione (GSH), catalase, and superoxide dismutase (SOD) activities. In addition, the neurotransmitter acetylcholine (Ach) and acetylcholine esterase (AchE) activities, as well as levels of the apolipoprotein E4 (APOE4); β-secretase, hyper phosphor-tau and β-amyloid 42; 3-hydroxy- 3-methyl glutaryl coenzyme A reductase (HMG CoA R)” and COX-II by immunoblotting assays in the brain tissue of neonates and their dams in all the studied groups. Result: A very significant amelioration in acetylcholine and acetylcholine esterase neurotransmitters, Alzheimer’s makers (β-amyloid), antioxidants (reduced glutathione (GSH) contents, catalase (CAT) and superoxide dismutase (SOD); and inflammatory cytokines in NASH model is observed upon administrating ipriflavone (IP) as a natural food supplement. The multifunctional activities of ipriflavone as an antioxidant, anti-inflammatory and anti-insulin resistance drug were discussed and correlated with other investigations. Conclusion: Regarding steatohepatitis, the present study confirmed the anti-inflammatory effects of the ipriflavone (IP). Therefore, future studies should focus on hepatic fatty acid uptake, hepatic lipogenesis, and fatty acid oxidation and the role of IP in regulating hepatic fat metabolism. In addition, natural products like IP could be combined with the highly used pharmaceutical drugs to reduce the side effects of nonalcoholic steatohepatitis, and minimize progression of dementia. Moreover, the present study supports further attempts to heal the neural dysfunction via antioxidant and anti-inflammatory cascade activities using ipriflavone (IP).

The HER2/neu has shown a potential role in the choice of active chemotherapy for breast tumors because of its prognostic relevance and putative role in predicting drug resistance. Moreover, suppressing DNA replication has become an attractive strategy for treating cancer patients. In this attempt, the present study aimed to prepare new series of bis-imidazolium-based saldach {H2(Et)2saldach (nBu-Im+-X–)2} and their cis-Pd(II) complexes (saldach = N,N′-bis-(salicylidene)-R,R-1,2-diaminocyclohexane; X = Cl, PF6, BF4) as anticancer agents. The in vitro cytotoxicity activity of new cis-Pd(II) complexes against human breast adenocarcinoma cell lines (MCF-7) revealed higher growth-inhibitory effect than the native ligands. They induced a significant decrease for the protein HER2/neu expression with p

Impaired lung epithelial cell regeneration following injury may contribute to the development of pulmonary fibrosis. Epithelial-mesenchymal transition (EMT) is a critical event in embryonic development, wound healing following injury, and even cancer progression. Previous studies have shown that the combination of transforming growth factor beta-1 (TGFβ1) and fibroblast growth factor 2 (FGF2) induces EMT during cancer metastasis. However, this synergy remains to be elucidated in inducing EMT associated with wound healing after injury. We set out this study to determine the effect of fibroblast growth factor 2 (FGF2) on TGFβ1-induced EMT in the human lung epithelium. BEAS-2B and A549 cells were treated with TGFβ1, FGF2, or both. EMT phenotype was investigated morphologically and by measuring mRNA expression levels; using quantitative real-time PCR. E-cadherin expression was assayed by western blot and immunofluorescence staining. Cell migration was confirmed using a wound-healing assay. TGFβ1 induced a morphological change and a significant increase in cell migration of BEAS-2B cells. TGFβ1 significantly reduced E-cadherin (CDH1) mRNA expression and markedly induced expression of N-cadherin (CDH2), tenascin C (TNC), fibronectin (FN), actin alpha 2 (ACTA2), and collagen I (COL1A1). While FGF2 alone did not significantly alter EMT gene expression, it enhanced TGFβ1-induced suppression of CDH1 and upregulation of ACTA2, but not TNC, FN, and CDH2. FGF2 significantly inhibited TGFβ1-induced COL1A1 expression. Furthermore, FGF2 maintained TGFβ1-induced morphologic changes and increased the migration of TGFβ1-treated cells. This study suggests a synergistic effect between TGFβ1 and FGF2 in inducing EMT in lung epithelial cells, which may play an important role in wound healing and tissue repair after injury.

Background: Epithelial-mesenchymal transition (EMT) is a critical event in wound healing and tissue repair following injury. Transforming growth factor beta-1 (TGFβ1) plays an important role in inducing EMT in lung epithelial cells in vitro and in vivo. As fibroblast growth factor-2 (FGF2) reverses TGFβ1-induced collagen I (COL1A1) and α-smooth muscle actin (Actin alpha 2; ACTA2) expression in primary mouse and human lung fibroblasts, we set out this study to determine the effect of FGF2 on TGFβ1-induced EMT in human lung epithelial cells. Methods: BEAS-2B and A549 cells were treated with recombinant FGF2 (2 nM) with or without TGFβ1 (2 ng/ml) for up to 4 days. The phenotypic alterations associated with EMT were assessed by quantitative real-time PCR and E-cadherin protein expression levels was assayed by western blot and immunofluorescence staining. Cell migration was confirmed using wound-healing assay. Results: TGFβ1 treatment led to significantly reduced expression of E-cadherin (CDH1) and markedly induced expression of mesenchymal proteins such as N-cadherin (CDH2), tenascin C (TNC), fibronectin (FN), ACTA2 and COL1A1. TGFβ1 also induced a morphological change and a significant increase in cell migration. FGF2 did not significantly alter EMT gene expression markers on its own, however enhanced TGFβ1-induced suppression of CDH1 and upregulation of ACTA2, but did not alter TNC, FN and CDH2 gene expression levels induced by TGFβ1. FGF2 maintained TGFβ1-induced morphologic changes as well as increased the migration of TGFβ1-treated cells. Furthermore, FGF2 treatment significantly inhibited TGFβ1-induced COL1A1 expression in both BEAS-2B and A549 cells. FGFR-specific tyrosine kinase inhibitor PD173074 blocked the synergism between these two growth factors. Conclusions: This study suggests a synergistic effect between TGFβ1 and FGF2 in inducing EMT, which may play an important role in wound healing and tissue repair after injury. Our findings provide insight into the effects of FGF2 following lung injury and in pulmonary fibrosis.

In this work, we have successfully upgraded the crab wastes into Pd(II) complex of Gboxin analog-chitooligosaccharides conjugate (Pd(II)COS@GbA). This new complex has a high capacity to inhibit the proliferation of prostate cancer cells (IC50 = 1.92 μg/ml). This activity could be attributed to its ability to induce mitochondrial fragmentation through increasing mitochondrial fission dynamin-related protein 1 (p

Heavy metals are reported as neurodegenerative disorders progenitor. They play a role in the precipitation of abnormal β-amyloid protein and hyper-phosphorylated tau, the main hallmarks of Alzheimer's disease (AD). The present study aimed to validate the heavy metals-induced Alzheimer's-like disease in rats as an experimental model of AD and explore the therapeutic effect of berberine via tracking its effect on the oxidative stress-inflammatory pathway. Alzheimer's-like disease was induced in rats orally by a mixture of aluminium, cadmium and fluoride for three months, followed by berberine treatment for another one month. Berberine significantly improved the cognitive behaviors in Morris water maze test and offered a protective effect against heavy metals-induced memory impairment. Docking results showed that berberine inhibited AChE, COX-2 and TACE. Matching with in silico study, berberine downregulated the AChE expression and inhibited its activity in the brain tissues. Also, it normalized the production of TNF- α, IL-12, IL-6 and IL-1β. Moreover, it evoked the production of antioxidant Aβ40 and inhibited the formation of Aβ42, responsible for the aggregations of amyloid-β plaques. Histopathological examination confirmed the neuroprotective effect of berberine. The present data advocate the possible beneficial effect of berberine as therapeutic modality for Alzheimer's disease via its antiinflammatory/antioxidant mechanism.

In the present study, we investigated the neurobiochemical alterations and oxidative stress induced by food preservative; sodium nitrite (NaNO2) as well as the role of the garlic oil in amelioration of the neurotoxicity in male albino rats. Serum and brain homogenates of the rats received NaNO2 (80 mg/kg body weight) for 3 months exhibited significant decrease in acetylcholine esterase (AChE) activity as well as the levels of phospholipids, total protein and the endogenous antioxidant system (glutathione; GSH and superoxide dismutase; SOD). In contrast, lactic dehydrogenase (LDH) activity, brain thiobarbituric acid reactive substances (TBARS) and nitric oxide (NO) levels were significantly increased. On the other hand, the oral administration of garlic oil (5 ml/kg body weight) daily for 3 months significantly improved the neurobiochemical disorders and inhibited the oxidative stress induced by NaNO2 ingestion. So, this study reveals the neural toxic effects of NaNO2 by exerting oxidative stress and retrograde the endogenous antioxidant system. However, garlic oil has a promising role in attenuating the obtained hazard effects of sodium nitrite by its high antioxidant properties which may eventually be related with the preservation of SOD activity and primary mitochondrial role against nitrite-induced neurotoxicity in rats.

The most abundant of the collagen protein family, type I collagen is encoded by the COL1A2 gene. The COL1A2 restriction fragment length polymorphisms (RFLPs) EcoRI, RsaI and MspI in samples from several different central-eastern Mediterranean populations were analysed and found to be potentially informative anthropogenetic markers.The objective was to define the genetic variability of COL1A2 in the central-eastern Mediterranean and to shed light on its genetic distribution in human groups over a wide geographic area.PCR-RFLP analysis of EcoRI, RsaI and MspI polymorphisms of the COL1A2 gene was performed on oral swab and blood samples from 308 individuals from the central-eastern Mediterranean Basin. The genetic similarities among these groups and other populations described in the literature were investigated through correspondence analysis.Single-marker data and haplotype frequencies seemed to suggest a genetic homogeneity within the European populations, whereas a certain degree of differentiation was noted for the Egyptians and the Turks.The genetic variability in the central-eastern Mediterranean area is probably a result of the geographical barrier of the Mediterranean Sea, which separated European and African populations over time.

Ionizing radiation is classified as a potent carcinogen, and its injury to living cells, in particular to DNA, is due to oxidative stress enhancing apoptotic cell death. Our present study aimed to characterize and semi-quantify the radiation-induced apoptosis in CNS and the activity of Mentha extracts as neuron-protective agent. Our results through flow cytometry exhibited the significant disturbance and arrest in cell cycle in % of M1: SubG1 phase, M2: G0/1 phase of diploid cycle, M3: S phase and M4: G2/M phase of cell cycle in brain tissue (p 0.05). Significant increase in % of apoptosis and P53 protein expression as apoptotic biomarkers were coincided with significant decrease in Bcl(2) as an anti-apoptotic marker. The biochemical analysis recorded a significant decrease in the levels of reduced glutathione, superoxide dismutase, deoxyribonucleic acid (DNA) and ribonucleic acid contents. Moreover, numerous histopathological alterations were detected in brain tissues of gamma irradiated mice such as signs of chromatolysis in pyramidal cells of cortex, nuclear vacuolation, numerous apoptotic cell, and neural degeneration. On the other hand, gamma irradiated mice pretreated with Mentha extract showed largely an improvement in all the above tested parameters through a homeostatic state for the content of brain apoptosis and stabilization of DNA cycle with a distinct improvement in cell cycle analysis and antioxidant defense system. Furthermore, the aforementioned effects of Mentha extracts through down-regulation of P53 expression and up-regulation of Bcl(2) domain protected brain structure from extensive damage. Therefore, Mentha extract seems to have a significant role to ameliorate the neuronal injury induced by gamma irradiation.

The damaging effect of ionizing radiation on body systems on one hand, and the development of radio-protective agents on the other hand, have gained increased attention in the last decades. In the present study, male Swiss albino mice exposed to six gray gamma irradiation, exhibited significant increase in brain thiobarbituric acid reactive substances (TBARS), nitric oxide (NO), and free radicals such as hydrogen peroxide (H2O2). Significant decrease in the levels of reduced glutathione (GSH), glutathione-S-transferase (GST), superoxide dismutase (SOD), deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) contents, acetylcholinestrase (AchE), and the neurotransmitters dopamine (DA), serotonin (5-HT), and acetylcholine (Ach), was also documented. In addition, the levels of serum electrolytes sodium (Na), calcium (Ca), zinc (Zn), magnesium (Mg), and cupper (Cu) decreased significantly, while the levels of potassium (K), and iron (Fe) increased significantly. Additionally, some Lewy body aggregations were detected. On the other hand, pretreatment of gamma irradiated mice with Mentha piperita extract (1g /1Kg body weight /day) significantly abolished radiation induced elevations of TBARS, NO, H2O2, K and Fe levels, as well as significantly ameliorated the GSH, GST, SOD, AchE, DNA, RNA, Na, Ca, Zn, Mn, Cu and the mentioned-above neurotransmitters levels. In conclusion, Mentha extract may provide a significant level of protection against radiation-induced oxidative stress. It might have improved the antioxidant defense system in pre-treated mice also. Key words: Gamma irradiation, Mentha piperita, oxidative stress, neuroprotective radioprotective agent, endogenous antioxidant system.