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The current study aimed to explore the pretreatment of bone marrow mesenchymal stem cells (BMSCs) with hyaluronic acid (HA) on renal fibrosis in Adriamycin- induced CKD in rats.Sixty male SD rats were alienated into 4 equal groups; The control group: rats received two saline injections at 1 and 14 days, adriamycin (ADR) group: rats were injected i.v. twice via tail vein at day one and after 2 weeks, BMSCs group; rats were injected i.v. twice after 5 days of each ADR injection, and HA+BMSCs; rats were i.v. injected twice with BMSCs pretreated with 1 mg/ml HA after 5 days of each ADR injection. Protective role of BMSCs on renal function and morphology was detected using biochemical analysis, molecular studies, histopathological, and immunohistohemical investigations.Pretreatment of BMSCs with HA showed significant decrease in KIM-1, and increase in serum albumin compared to CKD group (p 0.05). Moreover, it reduced the expression of the apoptotic marker Caspase-3, the inflammatory markers TNF and IL-6, and the fibrotic markers Wnt7a, β-catenin, and fibronectin1 than the CKD group (p 0.05).The current outcomes suggested that BMSCs preconditioned with HA could attenuate the renal fibrosis in adriamycin- induced CKD.

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).

Presented work deliberate the dosimetric impact of low absorbed dose in modified borate bioactive glass as utilization for such newly studied material. The particle size impact, glow curve, relative response to different doses, and dose fading impact was examined as thermoluminescence (TL) properties moreover. Thermoluminescence investigations of borate bioglass containing copper oxide irradiated by γ-ray demonstrated a conspicuous TL glow peak maximum at 353 °C. The TL emission peak due to defects identified with the host material. The outcoming results are concerned with their uses in low dose dosimetry. The outcoming showed that the ideal grain size is extended between 53 and 106 µm.), respecting to glow peak of borate bioactive glass after gamma irradiation from gamma radiation cobalt source, three unresolved glow peaks was founded. The linear relationship response curve in the portion runs from 0.1 up to 1.5 Gy. The absolute TL-signal seems to be constant through 30 days of storage of the modified samples. Peaks activation energies were calculated through TL kinetics in deep traps, which recommended store the TL-signal. The low detected with a threshold value (0.01 Gy) fusing with this strategy represented as a good radiation sensitivity making it permissible to use for individual accidental retrospective. However, in the case of a personal dosimeter, Good and helpful data can be gotten on. Treatment would then be able to be founded on this data moreover.

The toxicity of cisplatin (CDDP) toward the renal tubules and its severe effects on the proximal tubules limits its futher use for cancer therapy. The current study was undertaken to evaluate the protective effects of gallic acid-grafted O-carboxymethyl chitosan (GA@CMLMWC) against nephrotoxicity induced by CDDP in rats. Renal injury was assessed in the GA@CMLMWC/CDDP-treated rats using kidney injury molecule-1 (KIM-1). Moreover, the levels of reduced glutathione (GSH), malondialdehyde (MDA), and nitric oxide (NO) were measured. The comet assay was performed to measure the DNA damage. The renoprotective activity of GA@CMLMWC was supported by histo- and immuno-pathological studies of the kidney. GA@CMLMWC significantly normalized the increases in kidney homogenate of KIM-1, MDA, and NO-induced by CDDP and significantly increased GSH as compared with the CDDP group. GA@CMLMWC also significantly protects rat kidneys from CDDP-induced histo- and immuno-pathological changes. Both biochemical findings and histo- and immuno-pathological evidence showed the renoprotective potential of GA@CMLMWC against CDDP-induced oxidative stress, inflammation, and renal dysfunction in rats. In conclusion, GA@CMLMWC has been shown to mitigate the nephrotoxicity impact of CDDP in cancer therapy.

Asthmatics exhibit clinical fluctuations between manageable and treatment-resistant phenotypes as a worldwide socioeconomic health burden. Sonic Hedgehog (Shh) genes mediate regulatory pulmonary cell renewal in adults and contribute to the pathogenesis of high phenotypic asthma which depends mainly on T helper-2 (Th-2) cells and related cytokines. However, the exact pathophysiological roles of Shh molecular signalling in the Th-17-dependent low phenotypic allergic airway inflammation and asthma are not evidenced previously.Ovalbumin (OVA) and OVA/lipopolysaccharide (LPS)-sensitized and challenged BALB/c mice were enrolled currently to assess the Shh signalling proteins. Furthermore, the effects of vismodegib, a Smo inhibitor, on the modulation of Shh signalling were compared to dexamethasone. The asthma phenotypes were confirmed by serum total immunoglobulin-E (IgE), bronchoalveolar lavage (BAL) fluid white blood cell counts, lung interleukins, tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β1, and histopathological changes, and scoring.Mice challenged with OVA or OVA/LPS showed upregulated lung Shh, patched (Ptch1), smoothened (Smo), and Gli1 proteins. Vismodegib in the two experimental phenotypes of asthma showed reduced airway inflammation and remodelling. Additionally, vismodegib reduced the eosinophilia and neutrophilia reported in high and low asthma types, respectively. Moreover, vismodegib and dexamethasone exhibited negative feedback control throughout the enhanced Shh signalling cascades, including Shh, Ptch1, and Gli1 in several asthma models.In conclusion, Shh signalling partially elucidates the OVA/LPS-challenged mice with severe asthma, which proposes a new promising molecular therapeutic target. Furthermore, Smo inhibition by vismodegib has therapeutic potential in both experimental eosinophilic and neutrophilic allergic airway diseases.

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

In the present work, the Thermoluminescence (TL) properties of red sand sample collected from Nasr city, Cairo, Egypt was studied (the grain size effect, glow curve properties, dose response, batch homogeneity and fading). Surface morphology was studied using scanning electron microscopy (SEM). Chemical compositions of the red sand samples were estimated using X-ray fluorescence (XRF) machine. The analysis showed that the red sand sample mainly consisted of SiO2 (95.84%) and has feldspar which exhibits thermoluminescence. The experimental results illustrated that the optimum grain size ranges from 75 to150μm. After irradiation with γ-source (Co-60), the glow curves of the sample were found to have three peaks. The response curve has linearity in the dose range 10Gy – 2 kGy. Through 100 day, the total TL-signal fading reached 17%, but the dosimetric peak reached 12%. The measured activation energies of the peaks were deep enough to store the TL-signal. The pre-irradiation annealing at 800 °C for 1 h increased the TL sensitivity 2.295 times its original value. It could be concluded that the investigated samples could be used in environmental high γ-radiation measurements.

Background: Nephrotoxicity is considered one of the most serious and dose-limiting factors for restricting clinical use of Cisplatin and anticancer efficacy. Gallic acid is a non-toxic substance that has a wide range of therapeutic roles with high antioxidant activity. So, the present study aims to investigate the concurrent protective action of Gallic acid against inflammatory and oxidative damage caused by Cisplatin in rat kidneys. Material and methods: Thirty-two male albino rats were classified into four groups, eight per each as follows: Group 1 (Normal Control group): without treatment. Group 2 (Gallic acid group): healthy rats were given Gallic acid. Group 3 (Cisplatin group): healthy rats were injected with cisplatin. Group 4 (Gallic acid + Cisplatin) treated group. Kidney functions, Paraoxonase-1, and inflammatory cytokines such as Tumor Necrosis Factor α, respectively were determined. Results: Cisplatin was induced kidney damage with a high significance (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.

A novel anticancer and anti-inflammatory agent based on hybrid curcuminoid-Gboxin analog (FLLL49-GbA) and its macromolecular silver(I) complex (Ag(I)FLLL49-GbA) have successfully synthesized. In addition, chitosan nanoparticles (CNPs) were used to encapsulate this macromolecular complex, targeting enhancing its therapeutic effect and minimizing its side impacts. The encapsulated Ag(I) complex was significantly triggered apoptosis (P 0.05) with much more rapidly release of Ag(I)FLLL49-GbA from the CNPs at pH 5.3 than at pH 7.4, which is beneficial for cancer-targeted drug delivery. Free complex showed promising ability in preventing glucose uptake and lactate production coupled with cellular ATP depletion in cancer cells. Additionally, there was significant decrease in the inflammatory cytokines in breast cancer (MCF-7) and lung cancer (A549) cells with values of P 0.01 and P 0.001 after 24 h incubation. Furthermore, the death-inducing proteins have been significantly up-regulated (P 0.01 to P 0.001) after 36 h incubation of cancer cells. Consequently, the novel curcuminoid macromolecule showed significant feasibility in triggering the high expression of apoptotic caspases caspase 3, caspase 8, P53, and Bax (P 0.01 to P 0.001) after 48 h of chemotherapy. Noteworthy, the cytotoxicity of Ag(I)FLLL49-GbA was significantly increased toward cancer cells (MCF-7 A549), while, reduced toward normal cells (HeLa) after loading on chitosan Nano-vehicles.

Pulmonary fibrosis is a pathologic chronic lung disorder characterized by the deposition of extracellular matrix and damage to lung architecture. Models of pulmonary fibrosis were developed in several animal species. However, murine models are more common due to their low costs, availability and well characterized immune systems. Indeed, these murine models play an important role in understanding the biology of the diseases, deciphering the cellular and molecular mechanisms mediating pulmonary pathobiology and to explore novel therapeutic approaches. Although the majority of these models mimic certain characteristics of human idiopathic pulmonary fibrosis, most of them do not mimic other features especially those related to the progressive and irreversible nature of this disease. The present protocol describes the induction of a pulmonary fibrosis model in mice with bleomycin, which is a risk factor for human lung fibrosis. Specifically, we described the methodology of intratracheal instillation of bleomycin as well as the assessment methods of pulmonary fibrosis either histopathologically based on Ashcroft grading score or by quantitatively based on biochemical biomarkers. Moreover, we proposed a detailed readout that can determine the degree of lung injury in bronchoalveolar lavage fluids. We described different cellular and molecular markers such as by total protein concentration, total cell count, immune cell differential count, and the expression of pro-inflammatory mediators. We present this model as a reference for studies on the pulmonary fibrosis.

Fibroblast growth factor (FGF) signaling has been implicated in the pathogenesis of pulmonary fibrosis. Mice lacking FGF2 have increased mortality and impaired epithelial recovery after bleomycin exposure, supporting a protective or reparative function following lung injury. To determine whether FGF2 overexpression reduces bleomycin-induced injury, we developed an inducible genetic system to express FGF2 in type II pneumocytes. Double-transgenic (DTG) mice with doxycycline-inducible overexpression of human FGF2 (SPC-rtTA;TRE-hFGF2) or single-transgenic controls were administered intratracheal bleomycin and fed doxycycline chow, starting at either day 0 or day 7. In addition, wild-type mice received intratracheal or intravenous recombinant FGF2, starting at the time of bleomycin treatment. Compared to controls, doxycycline-induced DTG mice had decreased pulmonary fibrosis 21 days after bleomycin, as assessed by gene expression and histology. This beneficial effect was seen when FGF2 overexpression was induced at day 0 or day 7 after bleomycin. FGF2 overexpression did not alter epithelial gene expression, bronchoalveolar lavage cellularity or total protein. In vitro studies using primary mouse and human lung fibroblasts showed that FGF2 strongly inhibited baseline and TGFβ1-induced expression of alpha smooth muscle actin (αSMA), collagen, and connective tissue growth factor. While FGF2 did not suppress phosphorylation of Smad2 or Smad-dependent gene expression, FGF2 inhibited TGFβ1-induced stress fiber formation and serum response factor-dependent gene expression. FGF2 inhibition of stress fiber formation and αSMA requires FGF receptor 1 (FGFR1) and downstream MEK/ERK, but not AKT signaling. In summary, overexpression of FGF2 protects against bleomycin-induced pulmonary fibrosis in vivo and reverses TGFβ1-induced collagen and αSMA expression and stress fiber formation in lung fibroblasts in vitro, without affecting either inflammation or epithelial gene expression. Our results suggest that in the lung, FGF2 is antifibrotic in part through decreased collagen expression and fibroblast to myofibroblast differentiation. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

The evolutionary history of toad species of East-North of Africa and Arabian Peninsula is intricately connected with the complex geological tectonic waves in these regions and may give rise to strictly endemic species. A total of 39 individual species (18 from Egyptian species Sclerophrys regularis and 17 of Sclerophrys arabica and 4 of Duttaphrynus dhufarensis from Saudi Arabia) were investigated and sequenced for D-loop and 12S rRNA fragments of mtDNA (mitochondrial DNA). This study was carried out to study their genetic diversity and phylogeographic evolutionary lineages. Arabian Peninsula species revealed high genetic and haplotype diversity more than African species S. regularis. The neutrality tests negative value of Tajima’s D and Fu’s Fu for both S. regularis and S. arabica indicating their deviations from neutrality suggesting the recent population expansion after a bottleneck or selective sweep. By contrast, D. dhufarensis showed positive values may be due to the low frequency of polymorphisms and decreased population size or balancing selection. Molecular phylogeny study of tree building using D-loop gene fragment splits each species in a separate clade, but 12S rRNA coding gene fragment splits African species of toads away from the Arabian Peninsula species. Moreover, these results were supported by the absence of gene flow among the African and Arabian Peninsula species which may indicate their different evolutionary lineage. Our results revealed that the Red Sea together with the evolutionary history of the climate in this region may have highly discontinuity effects, which prevented the gene flow and extensive distribution among the Afro-Arabian amphibian species.

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

The human cytochrome P4501A1 (CYP1A1) enzyme plays an important role in the metabolism of xenobiotics and endogenous substrates. Because polymorphisms within the CYP1A1 gene have been shown to be associated with various cancer risks and with the predicting clinical efficacy of some chemotherapies in different populations, most studies focus on their clinical significance. We, however, were interested in evaluating whether the polymorphisms could be used to distinguish human populations. Four single nucleotide CYP1A1 polymorphisms (rs4646903/ g.75011641; rs1048943/g.75012985; g.75012235; and rs1799814/ g.75012987) were analysed via PCR-RFLP assay in 1,195 individuals of various human groups from all over the world. In order to gain a more complete view of the genetic variability of the CYP1A1 gene, different statistical analyses were performed upon the populations of the present study and upon the limited data gleaned from previously studied populations. The allele and haplotype frequencies vary among populations: the rs4646903 (C) and rs1048943 (G) have been found to be nearly always linked and were found at the highest frequencies in Native Americans, while the variant associated to the position g.75012235 was only detected in certain African populations. Our work clearly indicates that the CYP1A1 polymorphisms differ among populations and that the prediction of genotypes constitutes an important aspect of precision medicine since some variants were associated with certain cancers and rs1048943 show strong association with optimized chemotherapy. Moreover, the CYP1A1 gene plays an important role in the metabolism of xenobiotics and it is likely that its frequencies could be strongly influenced by environmental factors.

Fibroblast growth factor (FGF) signaling has been implicated in the pathogenesis of pulmonary fibrosis. Mice lacking FGF2 have increased mortality and impaired epithelial recovery after bleomycin exposure, supporting a protective or reparative function following lung injury. To determine whether FGF2 overexpression reduces bleomycin-induced injury, we developed an inducible genetic system to express FGF2 in type II pneumocytes. Double-transgenic (DTG) mice with doxycycline-inducible overexpression of human FGF2 (SPC-rtTA;TRE-hFGF2) or single-transgenic controls were administered intratracheal bleomycin and fed doxycycline chow, starting at either day 0 or day 7. In addition, wild-type mice received intratracheal or intravenous recombinant FGF2, starting at the time of bleomycin treatment. Compared to controls, doxycycline-induced DTG mice had decreased pulmonary fibrosis 21 days after bleomycin, as assessed by gene expression and histology. This beneficial effect was seen when FGF2 overexpression was induced at day 0 or day 7 after bleomycin. FGF2 overexpression did not alter epithelial gene expression, bronchoalveolar lavage cellularity or total protein. In vitro studies using primary mouse and human lung fibroblasts showed that FGF2 strongly inhibited baseline and TGFβ1-induced expression of alpha smooth muscle actin (αSMA), collagen, and connective tissue growth factor. While FGF2 did not suppress phosphorylation of Smad2 or Smad-dependent gene expression, FGF2 inhibited TGFβ1-induced stress fiber formation and serum response factor-dependent gene expression. FGF2 inhibition of stress fiber formation and αSMA requires FGF receptor 1 (FGFR1) and downstream MEK/ERK, but not AKT signaling. In summary, overexpression of FGF2 protects against bleomycin-induced pulmonary fibrosis in vivo and reverses TGFβ1-induced collagen and αSMA expression and stress fiber formation in lung fibroblasts in vitro, without affecting either inflammation or epithelial gene expression. Our results suggest that in the lung, FGF2 is antifibrotic in part through decreased collagen expression and fibroblast to myofibroblast differentiation. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John WileySons, Ltd.

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.

The synthesis of new bis-triphenylphosphonium-based dimethlysalphens (salphen = N,N`-bis-(salicylidene)-o-phenylenediimine) and their complexes (Pd(II)-salphens) for chemotherapeutic applications were reported. The in vitro anticancer efficacy of new compounds against human hepatocellular carcinoma (HepG2) cell lines demonstrated higher activity for Pd-complexes as compared with their parent ligands. Among tested compounds, Pd(II)-salphen3 was found to be the most potent one in the suppression of HepG2 proliferation (IC50 = 3.01 μM), ˜3-fold lower than the clinical drug (cisplatin, CDDP) (IC50 = 8.28 μM). The Pd(II)-salphens can effectively bind to CT-DNA via a non-covalent interaction (intercalation/ electrostatic) as revealed from the hyperchromism of 28–53% along with 3–6 nm bathochromism observed during the electronic absorption titration of Pd(II)-salphens with CT-DNA. On the other hand, the H-bonding and hydrophobic interactions play crucial roles in the binding of Pd(II)-salphens to BSA as indicating from the BSA fluorescence quenching by Pd(II) complexes. Noteworthy, Pd(II)-salphen3 displayed the highest reactivity towards DNA/ BSA with intrinsic binding constants (Kb/ KF) (3.01 × 105/ 2.95 × 106 M–1).

Article, Numerous studies have reported neuroprotective effects of pyruvate when given in systemic injections. Impaired glucose uptake and metabolism are found in Alzheimer’s disease (AD) and in AD mouse models. We tested whether dietary pyruvate supplementation is able to provide added energy supply to brain and thereby attenuate aging- or AD-related cognitive impairment. Mice received ~800 mg/kg/day Na-pyruvate in their chow for 2–6 months. In middle-aged wild-type mice and in 6.5-month-old APP/PS1 mice, pyruvate facilitated spatial learning and increased exploration of a novel odor. However, in passive avoidance task for fear memory, the treatment group was clearly impaired. Independent of age, long-term pyruvate increased explorative behavior, which likely explains the paradoxical impairment in passive avoidance. We also assessed pyruvate effects on body weight, muscle force, and endurance, and found no effects. Metabolic postmortem assays revealed increased energy compounds in nuclear magnetic resonance spectroscopy as well as increased brain glycogen storages in the pyruvate group. Pyruvate supplementation may counteract aging-related behavioral impairment, but its beneficial effect seems related to increased explorative activity rather than direct memory enhancement., published version, peerReviewed

In the present study we investigated the effect of the non-alcoholic fatty liver disease (NAFLD) on the alterations in the activity of neurotransmitters catabolizing enzymes and energy catabolising enzymes, prooxidants, endogenous antioxidants and proinflammatory cytokines in brain tissue of NAFLD rats. Rats were intraperitonealy injected with CCl4 solution at a dose of (0.021 mole/Kg, 20 μL, body weight) three times weekly for four weeks. Acetylcholine esterase (AChE), monoamine oxidase (MAO), prooxidant/ antioxidants status, ATPase, lipid profile and glucose level were estimated spectrophotometrically while inflammatory markers; interleukin 6 and tumor necrosis factor alpha (IL6 and TNF-α) and insulin were assessed by ELISA technique. Our results showed that the induced NAFLD and insulin resistance (IR) were accompanied with hyperglycemia and hyperlipidemia and lowered brain glucose level with elevated ATPase activity, prooxidant status (TBARS level, xanthine oxidase and cytochrome 2E1 activities), and inflammatory markers. Through the induction period AChE activity was significantly increased compared to control in blood, liver and brain tissues. Also, MAO activity was significantly increased in both brain and liver tissue but decreased in serum compared with control. These biochemical data were supported with pathophysiological analysis that showed severe neurodegeneration, pyknosis acuolations and cavitations. These observations warrant the reassessment of the conventional concept that the NAFLD with IR progression may induce disturbances in activities of neurotransmitters catabolising enzymes and energy production accompanied with oxidative stress and metabolic disorders, acting as relative risk factors for brain dysfunction and damage with the development of age-associated neurodegenerative diseases such as Alzheimer's disease.

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.

Berberine is a plant alkaloid that has several pharmacological effects such as antioxidant, antilipidemic, and anti-inflammatory effects. Nonalcoholic steatohepatitis (NASH) triggers different aspects of disorders such as impaired endogenous lipid metabolism, hypercholesterolemia, oxidative stress, and neurotoxicity. In this study, we examined the mechanism by which NASH induces neurotoxicity and the protective effect of berberine against both NASH and its associated neurotoxicity. NASH induced rats showed significant impairments in lipid metabolism with increased serum triglycerides, cholesterol, and low-density lipoprotein (LDL). The NASH induced group also demonstrated a significant oxidative stress which is characterized by increased TBARs level and decreased antioxidant capacity such as GSH and SOD levels. Moreover, the NASH induction was associated with inflammation which was demonstrated by increased TNFαand nitric oxide levels. Hyperglycemia and hyperinsulinemia were observed in the NASH induced group. Also, our results showed a significant increase in the expression of the acetylcholine esterase (AChE) and amyloid beta precursor protein (AβPP). These changes were significantly correlated with decreased insulin degrading enzyme (IDE) and beta-amyloid40(Aβ40) and increased beta-amyloid42(Aβ42) in the hippocampal region. Daily administration of berberine (50 mg/kg) for three weeks ameliorated oxidative stress, inflammation, hyperlipidemia, hyperglycemia, hyperinsulinemia, and the observed neurotoxicity.

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.