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2.
Int J Nanomedicine ; 15: 49-63, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32021164

RESUMO

Background: The emergence of multi drug-resistant (MDR) bacterial infections and cancer has necessitated the development and discovery of alternative eco-safe antibacterial and anticancer agents. Biogenic fabrication of metallic nanoparticles is an emerging discipline for production of nanoproducts that exert potent anticancer and antibacterial activity, and do not suffer from the limitations inherent in physiochemical synthesis methods. Methodology: In this study, we isolated, purified, and characterized a novel cyanobacteria extract (Desertifilum IPPAS B-1220) to utilize in biofabrication of silver nanoparticles (D-SNPs). D-SNPs were produced by adding Desertifilum extract to silver nitrate solution under controlled conditions. Biofabrication of D-SNPs was confirmed using a UV-Vis spectrophotometer. The resultant D-SNPs were characterized using XRD, FTIR, SEM, and TEM. The toxicity of D-SNPs against five pathogenic bacteria and three cancer cell lines (MCF-7, HepG2, and Caco-2) was evaluated. Results: Formation of D-SNPs was indicated by a color change from pale yellow to dark brown. The peak of the surface plasmon resonance of the D-SNPs was at 421 nm. The XRD detected the crystallinity of D-SNPs. FTIR showed that polysaccharides and proteins may have contributed to the biofabrication of D-SNPs. Under SEM and TEM, the D-SNPs were spherical with diameter ranges from 4.5 to 26 nm. The D-SNPs significantly suppressed the growth of five pathogenic bacteria, and exerted cytotoxic effects against MCF-7, HepG2, and Caco-2 cancer cells with IC50 values of 58, 32, and 90 µg/mL, respectively. Conclusion: These findings showed for the first time the potentiality of novel cyanobacteria strain Desertifilum IPPAS B-1220 to fabricate small SNPs that acted as potent anticancer and antibacterial material against different cancer cell lines and pathogenic bacterial strains. These findings encourage the researchers to focus on cyanobacteria in general and especially Desertifilum sp. IPPAS B-1220 for synthesizing different NPs that opening the window for new applications.

3.
Hypertens Pregnancy ; : 1-5, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32013623

RESUMO

Purpose: To assess the associations between preeclampsia, methylenetetrahydrofolate reductase (MTHFR) C677T, and reduced folate carrier-1 (RFC-1) G80A gene polymorphism in Sudanese women.Methods: A matched (for age and parity) case-control study was conducted in a tertiary hospital (Saad Abualila) in Khartoum, Sudan during February to September 2018. The cases were women with preeclampsia and healthy pregnant women were the controls (160 women in each arm of the study). Genotyping for MTHFR C677T and RFC-1 G80A was performed by polymerase chain reaction-restriction fragment length polymorphism.Results: . . The MTHFR C677T variation was significantly more frequent in women with preeclampsia (16.2%) than in healthy pregnant women (1.8%) (OR = 10.1, 95% CI = 3.0-34.2, P < 0.001). There was borderline significance in the RFC-1 G80A variation, which was present in 2.50% of women with preeclampsia, but was not found in healthy pregnant women (P = 0.052).Conclusions: A higher prevalence of MTHFR C677T polymorphism in women with preeclampsia compared with healthy pregnant women suggests involvement of this variation in preeclampsia in Sudan.

4.
PLoS One ; 15(1): e0227833, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31951631

RESUMO

The aim of this study is to characterize the antimicrobial resistance of Campylobacter jejuni recovered from diarrheal patients in Belgium, focusing on the genetic diversity of resistant strains and underlying molecular mechanisms of resistance among Campylobacter jejuni resistant strains isolated from diarrheal patients in Belgium. Susceptibility profile of 199 clinical C. jejuni isolates was determined by minimum inhibitory concentrations against six commonly-used antibiotics (ciprofloxacin, nalidixic acid, tetracycline, streptomycin, gentamicin, and erythromycin). High rates of resistance were observed against nalidixic acid (56.3%), ciprofloxacin (55.8%) and tetracycline (49.7%); these rates were similar to those obtained from different national reports in broilers intended for human consumption. Alternatively, lower resistance rates to streptomycin (4.5%) and erythromycin (2%), and absolute sensitivity to gentamicin were observed. C. jejuni isolates resistant to tetracycline or quinolones (ciprofloxacin and/or nalidixic acid) were screened for the presence of the tetO gene and the C257T mutation in the quinolone resistance determining region (QRDR) of the gyrase gene gyrA, respectively. Interestingly, some of the isolates that displayed phenotypic resistance to these antimicrobials lacked the corresponding genetic determinants. Among erythromycin-resistant isolates, a diverse array of potential molecular resistance mechanisms was investigated, including the presence of ermB and mutations in the 23S rRNA gene, the rplD and rplV ribosomal genes, and the regulatory region of the cmeABC operon. Two of the four erythromycin-resistant isolates harboured the A2075G transition mutation in the 23S rRNA gene; one of these isolates exhibited further mutations in rplD, rplV and in the cmeABC regulatory region. This study expands the current understanding of how different genetic determinants and particular clones shape the epidemiology of antimicrobial resistance in C. jejuni in Belgium. It also reveals many questions in need of further investigation, such as the role of other undetermined molecular mechanisms that may potentially contribute to the antimicrobial resistance of Campylobacter.

5.
Cells ; 9(1)2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31935962

RESUMO

Obesity is associated with the accumulation of dysfunctional adipose tissue that secretes several pro-inflammatory cytokines (adipocytokines). Recent studies have presented evidence that adipose tissues in obese individuals and animal models are hypoxic, which may result in upregulation and stabilization of the hypoxia inducible factor HIF1α. Epigenetic mechanisms such as DNA methylation enable the body to respond to microenvironmental changes such as hypoxia and may represent a mechanistic link between obesity-associated hypoxia and upregulated inflammatory adipocytokines. The purpose of this study was to investigate the role of hypoxia in modifying adipocytokine DNA methylation and subsequently adipocytokine expression. We suggested that this mechanism is mediated via the DNA demethylase, ten-eleven translocation-1 (TET1), transcription of which has been shown to be induced by HIF1α. To this end, we studied the effect of hypoxia (2% O2) in differentiated subcutaneous human adipocytes in the presence or absence of HIF1α stabilizer (Dimethyloxalylglycine (DMOG), 500 µM), HIF1α inhibitor (methyl 3-[[2-[4-(2-adamantyl) phenoxy] acetyl] amino]-4-hydroxybenzoate, 30 µM), or TET1-specific siRNA. Subjecting the adipocytes to hypoxia significantly induced HIF1α and TET1 protein levels. Moreover, hypoxia induced global hydroxymethylation, reduced adipocytokine DNA promoter methylation, and induced adipocytokine expression. These effects were abolished by either HIF1α inhibitor or TET1 gene silencing. The major hypoxia-responsive adipocytokines were leptin, interleukin-1 (IL6), IL1ß, tumor necrosis factor α (TNFα), and interferon γ (IFNγ). Overall, these data demonstrate an activation of the hydroxymethylation pathway mediated by TET1. This pathway contributes to promoter hypomethylation and gene upregulation of the inflammatory adipocytokines in adipocytes in response to hypoxia.

6.
Eur J Pharm Biopharm ; 148: 54-66, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31945489

RESUMO

A variety of hepatic insults result in the accumulation of collagen-rich new extracellular matrix in the liver, ultimately culminating in liver fibrosis and cirrhosis. For such reasons, approaches looking into digestion of the collagen-rich extracellular matrix present an interesting therapeutic approach for cases of chronic liver disease, where the fibrotic scar is well established. Portal collagenase administration has recently led to the successful reversion of cirrhosis in an experimental rabbit model. Notwithstanding, the question of how such a sensitive therapeutic macromolecule could be administered in a less invasive manner, and in a way that preserves its functionality and avoids digestion of other non-hepatic vital collagen presents itself. Chitosan is a biodegradable polymer that has been reported to interact and bind to collagen. Chitosan nanoparticles (CS NPs) have also been reported to encapsulate therapeutic proteins, maintaining their functional form and protecting them from in-vivo degradation. For such reasons, CS NPs were loaded with collagenase and evaluated in-vitro and in-vivo for their ability to target and digest collagen. CS NPs were able to encapsulate collagenase (≈ 60% encapsulation efficiency) and release its content in active form. To determine whether chitosan's collagen interaction would enable NP collagen binding or whether the modification with collagen binding peptides (CBPs) is necessary, CS NPs were modified with the CBP; CCQDSETRTFY. Since the density of targeting ligand and the length of tether play a significant role in the success of active targeting, the surface of NPs was modified with different densities of the CBP either directly or using a polyethylene glycol (PEG) spacer. PEGylated NPs showed higher levels of CBP tagging; high, intermediate and low density of CBPs corresponded to 585.8 ± 33, 252.9 ± 25.3 and 56.5 ± 8.8 µg/mL for PEGylated NPs and 425.56 ± 12.67, 107.91 ± 10.3 and 49.86 ± 3.2 µg/mL for unPEGylated NPs, respectively. In-vitro collagen binding experiments showed that unmodified CS NPs were able to bind collagen and that modification with CBPs either directly or via PEG did not enhance collagen binding. In-vivo experiments demonstrated that unmodified CS NPs were able to reverse fibrosis with a survival rate of 100% at the end of the study, indicating the ability of CS NPs to deliver functional collagenase to the fibrotic liver and making the use of CBPs unnecessary.

7.
Lasers Med Sci ; 35(1): 297, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31788745

RESUMO

After publication of this paper, the authors determined that the name of the author Tamer Mohamed Shosha was incorrectly spelled. The correct presentation should be Tamer Mohamed Shousha.

8.
Int J Pharm ; 575: 118886, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31790804

RESUMO

Drug crystallization in transdermal patches is still a major challenge, confronting the formulation development of topical drug delivery systems. Encapsulation of drugs into nanoparticles is proposed here as a promising tool for regulating drug crystallization in transdermal patches. The degree of recrystallization and transdermal permeation of ibuprofen and hydrocortisone loaded in polymeric and lipid nanoparticles from matrix-type transdermal patches were investigated. Ethyl cellulose (EC4), poly (lactide-co-glycolic acid) (PLGA) and polycaprolactone (PCL) were employed for polymeric nanoparticle preparations; while medium chain triglyceride (MCT) and witepsol were used for the preparation of MCT nanoemulsion and solid lipid nanoparticles (SLNs), respectively. As control, similar patches were prepared containing the free form of the investigated model drugs. All nanoparticle-containing transdermal patches exhibited less degree of drug recrystallization after 4 weeks compared to the control groups. Among the investigated nanocarriers, transdermal patches formulated with drug-loaded lipid nanoparticles showed the lowermost degree of recrystallization. Drug encapsulation into SLNs succeeded to reduce the degree of ibuprofen and hydrocortisone recrystallization from 23.3 ± 0.9 and 21.9 ± 1.2% to 0.2 ± 0.1 and 1.8 ± 0.1%, respectively. Additionally, the decreased crystalline fraction was accompanied by a corresponding increase in the drug flux through excised pig skin, which was found to be correlated to the hydrophobicity of the different nanocarriers. In conclusion, polymeric and lipid nanoparticles proved to be effective tools for the preparation of transdermal patches with on-demand drug loadings, while lowering the recrystallization risks. Moreover, the results of this study can be a valuable guidance for the design of effective transdermal patches by controlling the crystallization of various drugs through fine tuning of the carrier hydrophobicity.

9.
Menopause ; 27(2): 238-242, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31834160

RESUMO

Uterine fibroids (UFs) are benign tumors that arise from a single genetically altered mesenchymal stem cell under the influence of gonadal hormones. UFs are the most common benign gynecologic tumors in premenopausal women worldwide. It is estimated that nearly 70% to 80% of women will develop UFs at some point during their lifetime. UFs often present with abnormal uterine bleeding (AUB), pelvic fullness, and may have deleterious effects on fertility. The natural regression of UFs begins in menopause. This is, however, a generality as this pathology may still be present in this age group. Many clinicians are concerned about hormone therapy (HT) because of UFs regrowth; nevertheless, research of this subject remains inconclusive. If UFs are present in perimenopause or menopause, they typically manifest as AUB, which represents up to 70% of all gynecological consultations in perimenopausal and postmenopausal women. As AUB is a broad symptom and may not be specific to UFs, a thorough evaluation is required for correct diagnosis and proper treatment accordingly. Understanding the unique characteristics of the available treatment modalities is crucial in deciding the appropriate treatment approach. Decision on treatment modality should be made based on selection of the least morbidity and lowest risk for each patient. Multiple modalities are available; however, surgery remains the method of choice, with the best cure rates. Various attempts to create an inexpensive, safe, and effective drug for the treatments of UFs are still in the early stages of the clinical trials with some showing great promise. Treatment options include tibolone, aromatase inhibitors, selective estrogen receptor modulators, uterine artery embolization, and selective progesterone receptor modulators.

10.
J Colloid Interface Sci ; 560: 596-605, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31679784

RESUMO

HYPOTHESIS: When they are used alone, some polymers, such as polypropylene, Carnauba wax or polycarbonate allow the creation of superhydrophobic surfaces by spin coating or casting. On the other hand, some other polymers, such as polystyrene, polyvinylacetate or polychloroprene, are unable to render a superhydrophobic surface by these techniques. Using binary mixtures of these two types of polymers in a single common solvent, superhydrophobic composite surfaces can be created. We aim to show that superhydrophobicity is depending on the ratio between the two polymers in the initial blend and their intrinsic wettability. EXPERIMENTS: The transition towards superhydrophobicity is studied on composite surfaces made of various polymers. Surfaces are created with simple coating methods, such as casting or spin-coating, of polymer solutions and letting the solvent evaporate at ambient conditions. FINDINGS: Transitions are sharp and the amount of polypropylene in the blend to achieve superhydrophobicity decreases with the hydrophobicity of the second polymer. Topographic and wettability measurements are performed that show that both effects, topographical and chemical, interplay in the property of superhydrophobicity.

11.
Pathogens ; 8(4)2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31810359

RESUMO

Middle East Respiratory Syndrome Coronavirus (MERS-CoV) became a global human health threat since its first documentation in humans in 2012. An efficient vaccine for the prophylaxis of humans in hotspots of the infection (e.g., Saudi Arabia) is necessary but no commercial vaccines are yet approved. In this study, a chimeric DNA construct was designed to encode an influenza A/H1N1 NA protein which is flanking immunogenic amino acids (aa) 736-761 of MERS-CoV spike protein. Using the generated chimeric construct, a novel recombinant vaccine strain against pandemic influenza A virus (H1N1pdm09) and MERS-CoV was generated (chimeric bivalent 5 + 3). The chimeric bivalent 5 + 3 vaccine strain comprises a recombinant PR8-based vaccine, expressing the PB1, HA, and chimeric NA of pandemic 2009 H1N1. Interestingly, an increase in replication efficiency of the generated vaccine strain was observed when compared to the PR8-based 5 + 3 H1N1pdm09 vaccine strain that lacks the MERS-CoV spike peptide insert. In BALB/c mice, the inactivated chimeric bivalent vaccine induced potent and specific neutralizing antibodies against MERS-CoV and H1N1pdm09. This novel approach succeeded in developing a recombinant influenza virus with potential use as a bivalent vaccine against H1N1pdm09 and MERS-CoV. This approach provides a basis for the future development of chimeric influenza-based vaccines against MERS-CoV and other viruses.

12.
Saudi Med J ; 40(12): 1251-1255, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31828277

RESUMO

OBJECTIVES: To investigate the indications of first (non-repeated) cesarean deliveries, to categorize those indications into absolute and relative according to established guidelines of cesarean deliveries, and to compare the women with absolute and relative indications by demography and pregnancy-related attributes.  Methods: A cross-sectional analysis of delivery data between September and October 2018, at the Maternity and Children Hospital, Buraidah, Al-Qassim, Saudi Arabia. Indications for cesarean deliveries of 200 primary cases were abstracted and were categorized into 'absolute' and 'relative' according to the Association of the Scientific Medical Societies in Germany guidelines.  Results: The leading indications were fetal distress (27.5%), non-progression of labor (22.5%), breech presentation (18%), and failed initiation of labor (4.5%). Of the 200 cases, 26.5% had absolute indications, 50% had relative indications, and 23.5% had indications that were neither absolute nor relative. Women with absolute indications had lower mean gestational age and a higher proportion with greater than 3 gravida than women with relative indications (p less than 0.05). Conclusion: The most common indications for first time cesarean, in decreasing order of frequency, were fetal distress, non-progression of labor, and breech presentation.

13.
Sci Rep ; 9(1): 19354, 2019 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-31852968

RESUMO

In the present study, alkaline hydrothermally treated titania nanoparticles (TiO2-HT) are prepared and followed by calcination at different low temperatures to improve TiO2 activity under visible light. The prepared photocatalysts (PCs) are characterized by different tools. TiO2-HT is scrutinized for decontamination of para-nitrophenol (PNP) and hexavalent chromium ions (Cr6+ ions) under simulated sunlight. TiO2-HT-300 and TiO2-HT-400 PCs have nanosized particle with large surface area of 148 and 116.26 m2/g, respectively. Additionally, XRD and FTIR proved formation of nanocrystalline anatase TiO2. The different calcined TiO2-HT materials show lower adsorption capacity for PNP and Cr6+ ions. TiO2-HT-300 and HT-TiO2-400 PCs have higher reduction rate of PNP than that of uncalcined temperature titania (HT-TiO2-U) powder. Complete conversion of PNP is achieved at natural pH after 180 min over TiO2-HT-300. As well, TiO2-HT-300 exhibits a superior photocatalytic removal of Cr6+ ions. The enhanced photocatalytic efficacy is ascribed to the synergism between higher surface area and particle size (quantum effect) of TiO2-HT-300. As results, HO· radicals are the main key active species for the photocatalytic degradation of PNP over TiO2- HT-300 PC but contribution of O2- and h+ holes is minor. The used method for preparation of TiO2-HT-300 reduces the cost preparation as well as environmental impact reduction. Finally, low temperature-calcined TiO2 is promising visible light active and an efficient photocatalyst with lower environmental impact for detoxification of PNP and Cr6+ ions from water.

14.
Sci Rep ; 9(1): 19548, 2019 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-31863035

RESUMO

Obesity is a leading risk factor for type-2 diabetes. Diabetes often leads to the dysregulation of angiogenesis, although the mechanism is not fully understood. Previously, long noncoding RNAs (lncRNAs) have been found to modulate angiogenesis. In this study, we asked how the expression levels of lncRNAs change in endothelial cells in response to excessive palmitic acid treatment, an obesity-like condition. Bioinformatics analysis revealed that 305 protein-coding transcripts were upregulated and 70 were downregulated, while 64 lncRNAs were upregulated and 46 were downregulated. Gene ontology and pathway analysis identified endoplasmic reticulum stress, HIF-1 signaling, and Toll-like receptor signaling as enriched after palmitic acid treatment. Moreover, we newly report enrichment of AGE-RAGE signaling pathway in diabetic complications, IL-17 signaling, and cysteine and methionine metabolism by palmitic acid. One lncRNA, Colorectal Neoplasia Differentially Expressed (CRNDE), was selected for further investigation. Palmitic acid induces CRNDE expression by 1.9-fold. We observed that CRNDE knockdown decreases endothelial cell proliferation, migration, and capillary tube formation. These decreases are synergistic under palmitic acid stress. These data demonstrated that lncRNA CRNDE is a regulator of endothelial cell proliferation, migration, and tube formation in response to palmitic acid, and a potential target for therapies treating the complications of obesity-induced diabetes.

15.
Artigo em Inglês | MEDLINE | ID: mdl-31761932

RESUMO

CONTEXT: Uterine Fibroid (UF) is the most common benign tumor in myometrium (MM) of reproductive age women. However, mechanism underlying disease pathogenesis is largely unknown. OBJECTIVE: To explore the link between nuclear ß-catenin and UF phenotype and ß-catenin cross-talk with estrogen and histone deacetylases (HDACs). DESIGN: protein/RNA levels of ß-catenin (CTNNB1), its responsive markers [CyclinD1, c-Myc], Androgen receptor (AR), p27 and class-I HDACs were measured in matched UF/MM tissues or cell populations. Chemical inhibition/activation and genetic knockdown (KD) of CTNNB1 were performed and their effects on UF phenotype were measured. Anti-UF Effect of two HDAC inhibitors (HDACis) was evaluated. MAIN OUTCOME MEASURE: ß-catenin nuclear translocation in response to ß-catenin inhibition/activation, estrogen and HDACis in UF cells. RESULTS: UF tissues/cells showed significantly higher expression of nuclear ß-catenin, CyclinD1, C-Myc, and HDACs (1, 2, 3, 8) than MM. Estradiol induced ß-catenin nuclear-translocation and consequently its responsive genes in both MM and UF cells, while Estrogen receptor antagonist reversed this induction effect. Treatment with ß-catenin or HDAC inhibitors showed a dose dependent growth inhibition, while Wnt3a treatment increased proliferation compared to control. Chemical inhibition of ß-catenin decreased CyclinD1 and c-Myc expression levels, while ß-catenin activation increased same markers expression. Genetic KD of CTNNB1 resulted in marked decrease in ß-catenin, CyclinD1, C-Myc and AR expression. Treatment of UF cells with HDACis decreased nuclear ß-catenin, CyclinD1 and C-Myc expression. Moreover, HDACis induced UF cells apoptosis and cell cycle arrest. CONCLUSION: ß-catenin nuclear-translocation contributes to UF phenotype, ß-catenin signaling is modulated by estradiol and HDAC activity.

16.
Pathogens ; 8(4)2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31703251

RESUMO

Highly pathogenic avian influenza viruses (HPAIV) of the H5-subtype have circulated continuously in Egypt since 2006, resulting in numerous poultry outbreaks and considerable sporadic human infections. The extensive circulation and wide spread of these viruses in domestic poultry have resulted in various evolutionary changes with a dramatic impact on viral transmission ability to contact mammals including humans. The transmitted viruses are either (1) adapted well enough in their avian hosts to readily infect mammals, or (2) adapted in the new mammalian hosts to improve their fitness. In both cases, avian influenza viruses (AIVs) acquire various host-specific adaptations. These adaptive variations are not all well-known or thoroughly characterized. In this study, a phylogenetic algorithm based on the informational spectrum method, designated hereafter as ISM, was applied to analyze the affinity of H5-type HA proteins of Egyptian AIV isolates (2006-2015) towards human-type cell receptors. To characterize AIV H5-HA proteins displaying high ISM values reflecting an increased tendency of the HA towards human-type receptors, recombinant IV expressing monobasic, low pathogenic (LP) H5-HA versions in the background of the human influenza virus A/PR/8/1934(H1N1) (LP 7+1), were generated. These viruses were compared with a LP 7+1 expressing a monobasic H5-HA from a human origin virus isolate (human LP-7271), for their receptor binding specificity (ISM), in vitro replication efficiency and in vivo pathogenicity in mammals. Interestingly, using ISM analysis, we identified a LP 7+1 virus (LP-S10739C) expressing the monobasic H5-HA of AIV A/Chicken/Egypt/S10739C/2015(H5N1) that showed high affinity towards human-type receptors. This in silico prediction was reflected by a higher in vitro replication efficiency in mammalian cell cultures and a higher virulence in mice as compared with LP-7271. Sequence comparison between the LP-S10739C and the LP-7271 H5-HA, revealed distinct amino acid changes. Their contribution to the increased mammalian receptor propensity of LP-S10739C demands further investigation to better deduce the molecular determinant behind the reported high morbidity of 2014 to 2015 HPAI H5N1 virus in humans in Egypt. This study provides insights into the evolution of Egyptian H5 HPAIVs and highlights the need to identify the viral evolution in order to recognize emerging AIV with the potential to threaten human and animal populations.

17.
Brain Sci ; 9(11)2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31717715

RESUMO

OBJECTIVE: Brain damage, long-term disability and death are the dreadful consequences of ischemic stroke. It causes imbalance in the biochemical constituents that distorts the brain dynamics. Understanding the sub-cellular alterations associated with the stroke will contribute to deeper molecular understanding of brain plasticity and recovery. Current routine approaches examining lipid and protein biochemical changes post stoke can be difficult. Fourier Transform Infrared (FTIR) imaging spectroscopy can play a vital role in detecting these molecular alterations on a sub-cellular level due to its high spatial resolution, accuracy and sensitivity. This study investigates the biochemical and molecular changes in peri-infract zone (PIZ) (contiguous area not completely damaged by stroke) and ipsi-lesional white matter (WM) (right below the stroke and PIZ regions) nine weeks post photothrombotic ischemic stroke in rats. MATERIALS AND METHODS: FTIR imaging spectroscopy and transmission electron microscopy (TEM) techniques were applied to investigate brain tissue samples while hematoxylin and eosin (H&E) stained images of adjacent sections were prepared for comparison and examination the morphological changes post stroke. RESULTS: TEM results revealed shearing of myelin sheaths and loss of cell membrane, structure and integrity after ischemic stroke. FTIR results showed that ipsi-lesional PIZ and WM experienced reduction in total protein and total lipid content compared to contra-lesional hemisphere. The lipid/protein ratio reduced in PIZ and adjacent WM indicated lipid peroxidation, which results in lipid chain fragmentation and an increase in olefinic content. Protein structural change is observed in PIZ due to the shift from random coli and α-helical structures to ß-sheet conformation. CONCLUSION: FTIR imaging bio-spectroscopy provide novel biochemical information at sub-cellular levels that be difficult to be obtained by routine approaches. The results suggest that successful therapeutic strategy that is based on administration of anti-oxidant therapy, which could reduce and prevent neurotoxicity by scavenging the lipid peroxidation products. This approach will mitigate tissue damage in chronic ischemic period. FTIR imaging bio-spectroscopy can be used as a powerful tool and offer new approach in stroke and neurodegenerative diseases research.

18.
Viruses ; 11(11)2019 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-31717865

RESUMO

The surveillance and virological characterization of H5N8 avian influenza viruses are important in order to assess their zoonotic potential. The genetic analyses of the Egyptian H5N8 viruses isolated through active surveillance in wild birds and domestic poultry in the winter of 2016/2017 showed multiple introductions of reassortant viruses. In this study, we investigated and compared the growth kinetics, infectivity, and pathogenicity of the three reassortant forms of H5N8 viruses detected in wild birds and domestic poultry in Egypt during the first introduction wave in the winter of 2016/2017. Three representative H5N8 viruses (abbreviated as 813, 871, and 13666) were selected. The 871/H5N8 virus showed enhanced growth properties in vitro in Madin Darby canine kidney (MDCK) and A549 cells. Interestingly, all viruses replicated well in mice without prior adaptation. Infected C57BL/6 mice showed 20% mortality for 813/H5N8 and 60% mortality for 871/H5N8 and 13666/H5N8, which could be attributed to the genetic differences among the viruses. Studies on the pathogenicity in experimentally infected ducks revealed a range of pathogenic effects, with mortality rate ranging from 0% for 813/H5N8 and 13666/H5N8 to 28% for 871/H5N8. No significant differences were observed among the three compared viruses in infected chickens. Overall, different H5N8 viruses had variable biological characteristics, indicating a continuous need for surveillance and virus characterization efforts.

19.
Cytotechnology ; 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31722051

RESUMO

The present study aimed to investigate the osteoinductive potentiality of some selected nanostructures; Hydroxyapatite (HA-NPs), Gold (Au-NPs), Chitosan (C-NPs), Gold/hydroxyapatite (Au/HA-NPs) and Chitosan/hydroxyapatite (CH-NPs) on bone marrow- derived mesenchymal stem cells (BM-MSCs). These nanostructures were characterized using transmission electron microscope and Zetasizer. MSCs were isolated from bone marrow of rat femur bones and their identity was documented by morphology, flow cytometry and multi-potency capacity. The influence of the selected nanostructures on the viability, osteogenic differentiation and subsequent matrix mineralization of BM-MSCs was determined by MTT assay, molecular genetic analysis and alizarin red S staining, respectively. MTT analysis revealed insignificant toxicity of the tested nanostructures on BM-MSCs at concentrations ranged from 2 to 25 µg/ml over 48 h and 72 h incubation period. Notably, the tested nanostructures potentiate the osteogenic differentiation of BM-MSCs as evidenced by a prominent over-expression of runt-related transcription factor 2 (Runx-2) and bone morphogenetic protein 2 (BMP-2) genes after 7 days incubation. Moreover, the tested nanostructures induced matrix mineralization of BM-MSCs after 21 days as manifested by the formation of calcium nodules stained with alizarin red S. Conclusively, these data provide a compelling evidence for the functionality of the studied nanostructures as osteoinductive materials motivating the differentiation of BM-MSCs into osteoblasts with the most prominent effect observed with Au-NPs and Au/HA-NPs, followed by CH-NPs.

20.
Curr Mol Med ; 2019 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-31612831

RESUMO

Lifestyle factors, such as alcohol intake, have placed a substantial burden on public health. Alcohol consumption is increasing globally due to several factors including easy accessibility of this addictive substance besides its legal status and social acceptability. In the US, alcohol is the third leading preventable cause of death (after tobacco, poor diet and physical inactivity) with an estimated 88,000 people dying from alcohol-related causes annually, representing 1 in 10 deaths among working adults. Furthermore, the economic burden of excess drinking costs the US around $249 billion ($191.1 billion related to binge drinking). Although men likely drink more than women do, women are at much higher risk for alcohol-related problems. Alcohol use is also considered to be one of the most common non-communicable diseases, which affects reproductive health. This review article summarizes the current knowledge about alcohol-related pathogenesis of uterine fibroids (UFs) and highlights the molecular mechanisms that contribute to the development of UFs in response to alcohol consumption. Additionally, the effect of alcohol on the levels of various factors that are involved in UFs pathogenesis, such as steroid hormones, growth factors and cytokines, are summarized in this review. Animal studies of deleterious alcohol effect and future directions are discussed as well.

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