Holothuria polii Extract as a Potential Anticoccidial Agent: Evidence of Its MUC2 Regulatory Impact in Murine Jejunum.

Eimeria is a parasite that causes coccidiosis in a variety of animals, leading to nutritional imbalances, issues with food digestion and absorption, low weight, and intestinal inflammation of varying degrees in its hosts. Anticoccidial medication resistance has become a significant obstacle to disease control efforts, leading to a renewed focus on discovering novel chemicals for alternative therapeutic approaches. The purpose of this study was to determine the efficacy of Holothuria polii extract (HpE) in treating eimeriosis in mice. Five groups of mice were studied, with E. papillata sporulated oocysts (1 × 103) used to infect three groups experimentally. The first group was treated with 200 mg/kg of HpE, the second group with Amprolium (120 mg/kg), and the third group was left untreated as a control. The fourth and fifth groups were uninfected, with one of them treated with 200 mg/kg of HpE and the other used as a negative control. The results revealed that HpE has 10 phytochemical compounds according to GC-MS analysis. Treatment with HpE resulted in a substantial decrease in oocyst output in feces. Also, the parasitic stages showed morphometric alterations, with reductions in the measurements compared with the infected, untreated mice. Moreover, expression of the mucin gene (MUC2) was higher in treated mice compared to infected ones, with significant increases in goblet cell numbers, which provided additional evidence for the activity of HpE as an anticoccidial product. In conclusion, there are a wide variety of natural products and many have been employed in folk medicine for treating a range of parasitic diseases.

Proven anti-virulence therapies in combating methicillin- and vancomycin-resistant Staphylococcus aureus infections.

Introduction: Despite years of efforts to develop new antibiotics for eradicating multidrug-resistant (MDR) and multi-virulent Methicillin-Resistant Staphylococcus aureus (MRSA) and Vancomycin-Resistant Staphylococcus aureus (VRSA) infections, treatment failures and poor prognoses in most cases have been common. Therefore, there is an urgent need for new therapeutic approaches targeting virulence arrays. Our aim is to discover new anti-virulence therapies targeting MRSA and VRSA virulence arrays. Methodology: We employed phenotypic, molecular docking, and genetic studies to screen for anti-virulence activities among selected promising compounds: Coumarin, Simvastatin, and Ibuprofen. Results: We found that nearly all detected MRSA and VRSA strains exhibited MDR and multi-virulent profiles. The molecular docking results aligned with the phenotypic and genetic assessments of virulence production. Biofilm and hemolysin productions were inhibited, and all virulence genes were downregulated upon treatment with sub-minimum inhibitory concentration (sub-MIC) of these promising compounds. Ibuprofen was the most active compound, exhibiting the highest inhibition and downregulation of virulence gene products. Moreover, in vivo and histopathological studies confirmed these results. Interestingly, we observed a significant decrease in wound area and improvements in re-epithelialization and tissue organization in the Ibuprofen and antimicrobial treated group compared with the group treated with antimicrobial alone. These findings support the idea that a combination of Ibuprofen and antimicrobial drugs may offer a promising new therapy for MRSA and VRSA infections. Conclusion: We hope that our findings can be implemented in clinical practice to assist physicians in making the most suitable treatment decisions.

Impact of nano Fe2O3 on radiation parameters of epoxy reinforced with nano carbon.

This study aims to investigate the effectiveness of iron oxide (Fe2O3) and carbon black in micro and nanoscales incorporated into an epoxy adhesive matrix for gamma-ray attenuation. The composites were prepared via a simple and cost-effective synthesis method. The grain size of powder NPs was measured using a transmission electron microscope (TEM), and the particle size was about 20 ± 5 nm and 31.46 ± 2 nm for carbon and Fe2O3, respectively. The morphological properties were characterized by a scanning electron microscope, which indicated the excellent dispersion of NPs, which blocked almost all pores of the composite and increased the capability of radiation attenuation. In addition, the chemical composition of samples using energy dispersive X-rays (EDX) and the compressive strength were measured. Furthermore, the linear and mass attenuation coefficients were determined experimentally for incident photon energies of 59.51-1408.01 keV emitted from γ-ray sources using the sodium iodide scintillation detector NaI. A comparison was conducted between the experimental data and theoretical results that obtained from XCOM software, examined the validity of the experimental results. The relation deviation rate was found to vary between 0.0008 and 2.83%. Furthermore, the measurement of the relation deviation rate between the linear attenuation coefficients of micro and nano composites revealed a range of values between 1 and 25%. Also, shielding parameters such as half-value layer (HVL), tenth-value layer (TVL), mean free path (MFP), and effective atomic number (Zeff) were measured. Moreover, the equivalent atomic number (Zeq), absorption, and exposure buildup factors for prepared samples were calculated. The results showed that the incorporation of Fe2O3 NPs enhanced the shielding capability of the composites, as evidenced by the significant reduction in gamma-ray transmission. The composite materials exhibited excellent mechanical strength, making them suitable for practical applications in radiation shielding. Furthermore, it was determined that the elevation in N-Fe2O3 concentration resulted in a direct increase in the linear attenuation coefficient, from 0.314 to 0.519 cm-1 at 0.5951 MeV and from 0.099 to 0.124 cm-1 at 0.662 MeV. Nevertheless, a slight increase was discerned in the identified mass attenuation coefficients at 0.1332 and 0.1408 MeV. The experimental data for MFP, HVL, and TVL demonstrate that the EFeC4 sample exhibits optimal performance, with values of 1.9, 1.3, and 4.4 cm at 0.5951 MeV, and at 0.661 MeV, the values are 8.04, 5.57, and 18.52 cm, while at 0.1408 MeV, the values are 12.06, 8.36, and 27.78 cm, respectively. Overall, this research highlights the potential of iron oxide-carbon/epoxy composites as efficient and reliable materials for gamma-ray protection in various fields, including nuclear power plants, medical facilities, and space exploration.

Combining In Vitro, In Vivo, and Network Pharmacology Assays to Identify Targets and Molecular Mechanisms of Spirulina-Derived Biomolecules against Breast Cancer.

The current research employed an animal model of 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary gland carcinogenesis. The estrogen receptor-positive human breast adenocarcinoma cell line (MCF-7) was used for in vitro analysis. This was combined with a network pharmacology-based approach to assess the anticancer properties of Spirulina (SP) extract and understand its molecular mechanisms. The results showed that the administration of 1 g/kg of SP increased the antioxidant activity by raising levels of catalase (CAT) and superoxide dismutase (SOD), while decreasing the levels of malonaldehyde (MDA) and protein carbonyl. A histological examination revealed reduced tumor occurrence, decreased estrogen receptor expression, suppressed cell proliferation, and promoted apoptosis in SP protected animals. In addition, SP disrupted the G2/M phase of the MCF-7 cell cycle, inducing apoptosis and reactive oxygen species (ROS) accumulation. It also enhanced intrinsic apoptosis in MCF-7 cells by upregulating cytochrome c, Bax, caspase-8, caspase-9, and caspase-7 proteins, while downregulating Bcl-2 production. The main compounds identified in the LC-MS/MS study of SP were 7-hydroxycoumarin derivatives of cinnamic acid, hinokinin, valeric acid, and α-linolenic acid. These substances specifically targeted three important proteins: ERK1/2 MAPK, PI3K-protein kinase B (AKT), and the epidermal growth factor receptor (EGFR). Network analysis and molecular docking indicated a significant binding affinity between SP and these proteins. This was verified by Western blot analysis that revealed decreased protein levels of p-EGFR, p-ERK1/2, and p-AKT following SP administration. SP was finally reported to suppress MCF-7 cell growth and induce apoptosis by modulating the PI3K/AKT/EGFR and MAPK signaling pathways suggesting EGFR as a potential target of SP in breast cancer (BC) treatment.

Preparation and characterization of Sorafenib nano-emulsion: impact on pharmacokinetics and toxicity; an in vitro and in vivo study.

Hepatocellular carcinoma (HCC) ranks as the third leading cause of cancer-related deaths worldwide. Current treatment strategies include surgical resection, liver transplantation, liver-directed therapy, and systemic therapy. Sorafenib (Sor) is the first systemic drug authorized by the US Food and Drug Administration (FDA) for HCC treatment. Nevertheless, the conventional oral administration of Sor presents several limitations: poor solubility, low bioavailability, drug resistance development, and off-target tissue accumulation, leading to numerous adverse effects. Nano-emulsion, a nano-delivery system, is a viable carrier for poorly water-soluble drugs. It aims to enhance drug bioavailability, target organ accumulation, and reduce off-target tissue exposure, thus improving therapeutic outcomes while minimizing side effects. This study formulated Sor nano-emulsion (Sor NanoEm) using the homogenization technique. The resultant nano-emulsion was characterized by particle size (121.75 ± 12 nm), polydispersity index (PDI; 0.310), zeta potential (-12.33 ± 1.34 mV), viscosity (34,776 ± 3276 CPs), and pH (4.38 ± 0.3). Transmission Electron Microscopy exhibited spherical nano-droplets with no aggregation signs indicating stability. Furthermore, the encapsulation of Sor within the nano-emulsion sustained its release, potentially reducing the frequency of therapeutic doses. Cytotoxicity assessments on the HepG2 cell line revealed that Sor NanoEm had a significantly (P < 0.05) more potent cytotoxic effect compared to Sor suspension. Subsequent tests highlighted superior pharmacokinetic parameters and reduced dosage requirements of Sor NanoEm in mice. It exhibited an enhanced safety profile, particularly in behavior, brain, and liver, compared to its suspended form. These findings underscore the enhanced pharmacological and toxicological attributes of Sor Nano-emulsion, suggesting its potential utility in HCC treatment.

A comparative randomized clinical trial evaluating the efficacy and safety of tacrolimus versus hydrocortisone as a topical treatment of atopic dermatitis in children.

Background: Atopic dermatitis (AD) aetiology is not exactly identified, but it is characterized by pruritic skin reactions with elevation in the levels of inflammatory markers. Despite the fact that Corticosteroids are the mainstay therapy in the management of AD, they have many local and systemic adverse effects. Objective: The aim of this study is to evaluate the efficacy and safety of topical tacrolimus ointment in comparison to topical hydrocortisone cream in the management of the AD of children diagnosed with AD. Patients and Methods: This study was conducted on 200 children with AD. They were simply randomized into two groups, the tacrolimus group treated with 0.03% topical tacrolimus ointment and the hydrocortisone group treated with 1% hydrocortisone cream twice daily during the 3 weeks study period. Results: At the end of the study, both the tacrolimus and hydrocortisone groups showed a significant decline in the mean serum level of IL-10, IL-17, and IL-23 (p < 0.05) when compared to their baseline levels. However, the tacrolimus group showed a more significant decrease (p < 0.05) in the mean serum level of IL-10, IL-17, and IL-23 as compared to the hydrocortisone group [Mean differences = 1.600, 95% CI: 0.9858-2.214; 1.300, 95% CI: 1.086-1.514 and 4.200, 95% CI: 3.321-5.079]. Moreover, the median mEASI decreased similarly from 32 to 21 in the tacrolimus group and from 30 to 22 in the hydrocortisone group (p > 0.05) [Median difference = -2.000, 95% CI: -2.651 to -1.349; Median difference = 1.000, 95% CI: 0.3489-1.651]. Mild to moderate transient stinging and erythema were the main adverse effects that showed higher incidence in the tacrolimus group than in the hydrocortisone group (p < 0.05). In most cases, they resolved within 3-4 days. Besides, tacrolimus ointment did not cause skin atrophy as compared to the hydrocortisone group (p < 0.05). Conclusion: Tacrolimus ointment is more beneficial than hydrocortisone cream in managing AD in children in terms of lowering the inflammatory markers, however, there is no difference on the dermatitis severity scale. Moreover, tacrolimus is safer with a better side effect profile compared to hydrocortisone. Trial Registration: The trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT05324618).

Formulation, optimization, in-vivo biodistribution studies and histopathological safety assessment of duloxetine HCl-loaded ultra-elastic nanovesicles for antidepressant effect after intranasal and transdermal delivery.

Duloxetine hydrochloride (DUL) is a BCS class-II antidepressant drug, acting via serotonin and norepinephrine reuptake inhibition. Despite high oral absorption, DUL suffers limited bioavailability due to extensive gastric and first-pass metabolism. To improve DUL's bioavailability; DUL-loaded elastosomes were developed, via full factorial design, utilizing various span®60: cholesterol ratios, edge activator types and amounts. Entrapment efficiency (E.E.%), particle size (PS), zeta potential (ZP) and in-vitro released percentages after 0.5 h (Q0.5h) and 8 h (Q8h) were evaluated. Optimum elastosomes (DUL-E1) were assessed for morphology, deformability index, drug crystallinity and stability. DUL pharmacokinetics were evaluated in rats following intranasal and transdermal application of DUL-E1 elastosomal gel. DUL-E1 elastosomes [comprising span®60 and cholesterol (1:1) and brij S2 (edge activator; 5 mg)] were optimum with high E.E.% (81.5 ± 3.2%), small PS (432 ± 13.2 nm), ZP (-30.8 ± 3.3 mV), acceptable Q0.5h (15.6 ± 0.9%), and high Q8h (79.3 ± 3.8%). Intranasal and transdermal DUL-E1 elastosomes revealed significantly higher Cmax (251 ± 18.6 and 248 ± 15.9 ng/mL) at Tmax (2 and 4 h) and improved relative bioavailability (≈ 2.8 and 3.1 folds) respectively, in comparison to oral DUL aqueous solution. In-vivo histopathological studies were conducted to ensure the safety of DUL-E1. Elastosomes are promising novel nano-carriers, capable of enhancing the bioavailability of DUL via various routes of administration.

The effect of high oral loading dose of cholecalciferol in non-alcoholic fatty liver disease patients. A randomized placebo controlled trial.

Background and Aim: Non-alcoholic fatty liver (NAFLD) is one of the most common progressive metabolic disorders worldwide. There are increasing scientific interests nowadays for the association between vitamin D status and Non-alcoholic fatty liver. Earlier studies have revealed that vitamin D deficiency is highly prevalent in Non-alcoholic fatty liver patients that contributes to poor outcomes. Hence, the present study aimed to assess the efficacy and safety of oral cholecalciferol on Non-alcoholic fatty liver patients. Subjects and Methods: This study was conducted on 140 patients that were randomized either to group 1 that received the standard conventional therapy in addition to placebo or group 2 that received the standard conventional therapy in addition to cholecalciferol during the 4 months study period. Results: At the end of the study group 2 revealed significant decrease (p < 0.05) in the mean serum level of TG, LDL-C, TC, hsCRP as compared to their baseline results and group 1 results. Additionally, a significant improvement in the serum levels of ALT (p = 0.001) was seen in group 2 at the end of the study when compared to group 1. Whereas group 1 did not show any change in these parameters when compared to group 2 and their baseline results. Conclusion: Cholecalciferol was shown to have beneficial effects on serum ALT levels, hsCRP levels and lipid profile of NAFLD patients. Clinical Trial Registration: https://prsinfo.clinicaltrials.gov/prs-users-guide.html, identifier NCT05613192.

Adapted Evidence-Based Clinical Practice Guidelines for Diagnosis and Treatment of Epilepsies in Children: A Tertiary Children's Hospital Update.

HYPOTHESIS AND/OR BACKGROUND: We recently updated and merged the adapted clinical practice guidelines (CPGs) for the diagnosis and treatment of children with epilepsy of a tertiary-level hospital. Medical knowledge is always evolving. As a result, it is critical to revisit the clinical standards on a frequent basis to ensure that the best services are offered to the target receivers. The purpose of this article was to update and merge the CPGs at Alexandria University Children Hospital (AUCH) for the diagnosis (2014) and treatment (2016) of children with epilepsy to unify and standardize the practice for better care and outcome. METHODS: This review and update CPG project was initiated by assembling a Guideline Review Group (GRG). The GRG conducted focus group discussions and decided to search any published updates of the recommendations of the previously identified high-quality and evidence-based CPG developed by the SIGN (Scottish Intercollegiate Guidelines Network) and to merge the two previous local CPGs under one comprehensive CPG for full management of epilepsy in children. The high quality of the selected source CPG from SIGN was based on quality assessment of CPGs undertaken previously using the Appraisal of Guidelines for Research and Evaluation II Instrument. The GRG followed the Checklist for the Reporting of Updated Guidelines (CheckUp), which is the CPG tool recommended by the Enhancing the Quality and Transparency of health Research Network for reporting of updated CPGs in addition to the RIGHT-Ad@pt Checklist for Adapted CPGs. The finalized updated CPG draft was sent to the external reviewer group topic experts. RESULTS: The group updated 10 main categories of recommendations from one source CPG (SIGN). The recommendations included (1) epilepsy diagnosis; (2) recognition, identification, and referral; (3) pharmacological treatment of epilepsy and epilepsy syndromes; (4) nonpharmacological treatment of epilepsy and epilepsy syndromes; (5) managing pharmacoresistant epilepsy; (6) management of epilepsy in special groups; (7) medications; (8) children and caregiver education and support; (9) comorbidities and mortality; and (10) transitional care from pediatric to adult care services. CONCLUSIONS: The finalized CPG provides evidence-based guidance to health care providers in AUCH for the diagnosis and management of epilepsy in children. The study also established the significance of a collaborative clinical and methodological expert group for the update of CPGs, as well as the usability of the "CheckUp" and "RIGHT-Ad@pt" CPG Tools.

Organic acidurias in Egyptian children: The urge for high-risk screening.

BACKGROUND: Organic acidurias are a group of inborn errors of metabolism. They present a significant diagnostic challenge and are associated with serious morbidity and mortality. They are considered the most frequent inborn errors of metabolism among high-risk children. Gas chromatography-mass spectrometry is a reliable diagnostic technique for organic acidurias. This hospital-based study aimed to quantify the frequency of organic acidurias among a group of high-risk Egyptian pediatric patients and to highlight the importance of high-risk screening for such disorders. METHODS: One hundred and fifty high-risk children who presented to the inherited metabolic disease unit and the pediatric intensive care units of Cairo University Children Hospital were tested for urine organic acids using gas chromatography-mass spectrometry. RESULTS: Thirty percent (45/150) of the patients were confirmed as having an altered organic acids profile. Neurological manifestations were the most common presentation. Glutaric aciduria type I and maple-syrup urine disease were the most common disorders encountered among the group that was studied. CONCLUSION: Organic acid detection by gas chromatography-mass spectrometry is key to the diagnosis of many metabolic disorders. Until a national expanded newborn screening program is established, high-risk screening is strongly encouraged for the early detection of, and proper intervention for such disorders among Egyptian children.

Detection of soluble urokinase type plasminogen activator receptors in children with gingivitis and normal subjects.

BACKGROUND: Gingivitis is a reversible condition; however, if left untreated, it progresses to periodontitis, which a serious infection that leads to bone destruction. Soluble urokinase-type plasminogen activator receptor (suPAR) measurement may be of value in the early assessment of gingivitis in children, thereby minimizing risk of tooth loss. OBJECTIVES: In this observational study, we assessed salivary and serum concentrations of suPAR for the diagnosis of gingivitis and correlation of salivary suPAR with the periodontal clinical parameters. METHODS: Ninety children participated in the study, with 20 healthy subjects as controls and 70 patients with gingivitis. The gingivitis group was divided into mild, moderate, and severe cases. According to the gingival index (GI), salivary and serum samples were analyzed for the suPAR and C-reactive protein levels using an enzyme-linked immunosorbent assay. RESULTS: The salivary suPAR was significantly higher in patients with gingivitis (10.8 ± 2.9 ng/mL) than in the control group (7.0 ± 1.1 ng/mL) as P < 0.001. SuPAR was correlated with gingivitis severity. It was 7.7 ± 1.5 1 ng/mL in mild cases, 10.9 ± 1.2 ng/mL in moderate cases, and 14.4 ± 0.9 ng/mL in severe cases. The difference was significantly high (P < 0.001) between the groups; however, the difference between the mild cases and the control was nonsignificant as P < 0.066. The salivary suPAR was correlated with periodontal clinical parameters, which included GI and simple oral hygiene index (SOHI). Conversely the serum suPAR was not correlated with the salivary suPAR or the periodontal clinical parameters. CONCLUSION: The results of the present study demonstrated that the salivary suPAR is increased in proportionate with the degree of severity of gingivitis in children. Moreover, salivary suPAR was correlated with the periodontal clinical parameters.

Evaluating the neuroprotective activities of vinpocetine, punicalagin, niacin and vitamin E against behavioural and motor disabilities of manganese-induced Parkinson's disease in Sprague Dawley rats.

The current study investigated the neuroprotective activity of some drugs and nutriceuticals with antioxidant and anti-inflammatory potential on the pathogenesis of Parkinson's disease (PD). Rats were categorized into seven groups: Rats received tween80 daily for 5 weeks as a control group, MnCl2 (10 mg/kg, i.p) either alone (group II) or in combination with vinpocetine (VIN) (20 mg/kg) (group III), punicalagin (PUN) (30 mg/kg) (group IV), niacin (85 mg/kg) (group V), vitamin E (Vit E) (100 mg/kg) (group VI) or their combination (group VII). Motor activities was examined using open-field and catalepsy. Striatal monamines, acetylcholinesterase, excitatory/inhibitory neurotransmitters, redox status, pro-oxidant content, brain inflammatory, apoptotic and antioxidant biomarkers levels were assessed. Besides, histopathological investigations of different brain regions were determined. Groups (IV -GVII) showed improved motor functions of PD rats. Applied drugs significantly increased the brain levels of monoamines with the strongest effect to PUN. Meanwhile, they significantly decreased levels of acetylcholinesterase with a strongest effect to PUN. Moreover, they exhibited significant neuronal protection and anti-inflammatory abilities through significant reduction of the brain levels of COX2, TNF-α and Il-1ß with a strongest effect to the PUN. Interestingly; groups (IV - GVII) showed restored glutamate/GABA balance and exhibited a pronounced decrease in caspase-3 content and GSK-3ß protein expression levels. In addition, they significantly increased Bcl2 mRNA expression levels with a strongest effect for PUN. All these findings were further confirmed by the histopathological examinations. As a conclusion, we propose VIN and PUN to mitigate the progression of PD via their antioxidant, anti-inflammatory, anti-apoptotic, neurotrophic and neurogenic activities.

Psychometric properties of an Arabic translation of the quality of life in childhood epilepsy questionnaire (QOLCE-55).

OBJECTIVE: To develop an Arabic translation of the Quality of Life in Children with Epilepsy-55 questionnaire (QOLCE-55), and to assess its validity and reliability to be readily used in Arabic and Egyptian cultures. SUBJECTS AND METHODS: The original English version of the QOLCE-55 was translated into Arabic using a forward-backward translation method, and then a cross-sectional survey was conducted including 100 children with epilepsy aged 4-18 years. Caregivers of children completed the Arabic version of the QOLCE-55. Assessment of psychometric properties of the translated questionnaire was conducted using test-retest reliability, internal consistency, and convergent and divergent validity. RESULTS: The translated questionnaire showed excellent test-retest reliability with the intra-class correlation coefficient for all questionnaire domains, as well as the overall questionnaire ranging from 0.91 to 0.98. Cronbach alpha exceeded 0.7 denoting good internal consistency except for the emotional functioning scale. Convergent and divergent validity assessment showed that items of all domains significantly correlated with their scale scores with r > 0.4 and these correlations were much higher than correlations with other scales' scores, consistent with good convergent and divergent validity. The mean total HRQOL score was 65.63 ±â€¯8.79 with the highest score for social functioning domain and lowest score for physical functioning domain. CONCLUSION: The Arabic version of the QOLCE-55 can be considered a suitable, reliable, and valid tool to assess the HRQOL of children with epilepsy through their caregivers' reports.

Synthesis and biological evaluation of halogenated phenoxychalcones and their corresponding pyrazolines as cytotoxic agents in human breast cancer.

Novel halogenated phenoxychalcones 2a-f and their corresponding N-acetylpyrazolines 3a-f were synthesised and evaluated for their anticancer activities against breast cancer cell line (MCF-7) and normal breast cell line (MCF-10a), compared with staurosporine. All compounds showed moderate to good cytotoxic activity when compared to control. Compound 2c was the most active, with IC50 = 1.52 µM and selectivity index = 15.24. Also, chalcone 2f showed significant cytotoxic activity with IC50 = 1.87 µM and selectivity index = 11.03. Compound 2c decreased both total mitogen activated protein kinase (p38α MAPK) and phosphorylated enzyme in MCF-7 cells, suggesting its ability to decrease cell proliferation and survival. It also showed the ability to induce ROS in MCF-7 treated cells. Compound 2c exhibited apoptotic behaviour in MCF-7 cells due to cell accumulation in G2/M phase and elevation in late apoptosis 57.78-fold more than control. Docking studies showed that compounds 2c and 2f interact with p38alpha MAPK active sites.

Design, synthesis and evaluation of anticancer activity of new pyrazoline derivatives by down-regulation of VEGF: Molecular docking and apoptosis inducing activity.

Two series of pyrazoline compounds were designed and synthesized as antiproliferative agents by VEGFR pathway inhibition. All synthesized compounds were screened by the National Cancer Institute (NCI), Bethesda, USA for anticancer activity against 60 human cancer cell lines. Compound 3f exhibited the highest anticancer activity on the ovarian cell line (OVCAR-4) with IC50 = 0.29 µM and on the breast cell line (MDA-MB-468) with IC50 = 0.35 µM. It also exhibited the highest selectivity index (SI = 74). Compound 3f caused cell cycle arrest in OVCAR-4 cell line at the S phase which consequently inhibited cell proliferation and induced apoptosis. Moreover, 3f showed potent down-regulation of VEGF and p-VEGFR-2. Docking studies showed that compound 3f interacts in a similar pattern to axitinib on the VEGFR-2 receptor. The same compound was also able to fit into the gorge of STAT3 binding site, the transcription factor for VEGF, which explains the VEGF down-regulation.

The influence of vinpocetine alone or in combination with Epigallocatechin-3-gallate, Coenzyme COQ10, Vitamin E and Selenium as a potential neuroprotective combination against aluminium-induced Alzheimer's disease in Wistar Albino Rats.

Alzheimer's disease (AD) is one of such diseases that represent the most prominent cause of dementia in elderly people. To explore the possible neuroprotective effect as well as mechanism of action of Vinpocetine either alone or in combination with EGCG, CoQ10, or VE & Se in ameliorating aluminum chloride-induced AD in rats. Rats were received AlCl3 (70 mg/kg) intraperitoneal daily dose for 30 days along with EGCG (10 mg/kg, I.P), CoQ10 (200 mg/kg, P.O), VE (100 mg/kg, P.O) & Se (1 mg/kg, P.O) as well as Vinpocetine (20 mg/kg, P.O) either alone or in combination. Results revealed that the combination of Vinpocetine with EGCG showed the best neuroprotection. This protection in the brain was indicated by the significant decrease in Aß and ACHE. The same pattern of results were shown in the levels of monoamines and BDNF. In addition, the combination of Vinpocetine with EGCG showed more pronounced anti-inflammatory (TNF-α, IL-1ß) and antioxidant (MDA, SOD, TAC) effects in comparison to other combinations. These results were confirmed using histopathological examinations as well as DNA fragmentation assays. Vinpocetine with EGCG showed pronounced protection on neurons against AD induced by AlCl3 in rats.

Behavioral, Biochemical and Histopathological effects of Standardised Pomegranate extract with Vinpocetine, Propolis or Cocoa in a rat model of Parkinson's disease.

INTRODUCTION: Parkinsonism is a neurodegenerative disorder. Pomegranate (POM) has been previously shown to have a dopaminergic neuroprotective effect against parkinsonism. OBJECTIVE: The aim of the current study is to investigate the possible effect of POM in combination with each of vinpocetine, propolis, or cocoa in the treatment of parkinsonism disease even without being given as adjuvant to L-dopa . METHODS: Rats were divided into seven groups, one normal and six RT model groups. One of the RT groups (2.5 mg/kg/48 h/10 doses sc), for 20 days served as non-treated parkinsonism model, whereas the others were treated with either L-dopa (10 mg/kg, p.o./day) or with POM (150 mg/kg, p.o./day) together with each of the following; vinpocetine (VIN) (20 mg/kg, p.o./day), propolis (300 mg/kg, p.o./day), cocoa (24 mg/kg, p.o./day). Motor and cognitive performances were examined using four tests (catalepsy, swimming, Y-maze, open field). Striatal dopamine, norepinephrine, serotonin, GABA, glutamate, acetylcholinesterase, GSK-3ß, BDNF levels were assessed as well as MDA, SOD, TAC, IL-1ß, TNF-α, iNOs, and caspase-3. Also, histopathological examinations of different brain regions were determined. RESULTS: Treatment with L-dopa alone or with all POM combination groups alleviated the deficits in locomotor activities, cognition, neurotransmitter levels, acetylcholinesterase activity, oxidative stress, and inflammatory markers as well as caspase-3 expression induced by RT. CONCLUSION: Combinations of POM with each of VIN, propolis, or cocoa have a promising disease-modifying antiparkinsonian therapy even without being given as an adjuvant to L-dopa.

Murine liver response to Allium sativum treatment during infection induced-trypanosomiasis.

Hepatic injury induced by trypanosomiasis is one of the major health problems not only to human but also to wild and domestic animals. This study aimed to evaluate the hepatoprotective role of Allium sativum extract (ASE) against Trypanosoma evansi infection in mice. Animals were divided into 4 groups. Group I received only saline while group II received ASE (20 mg/Kg). Animals of group III and group IV were infected with T. evansi. The latter group was treated with ASE. The infrared spectroscopic analysis of A. sativum extract exhibited bands between 3700 cm-1 and 599 cm-1. On day 4 post T. evansi infection, ASE decreased the parasitemia by about 15 fold. Also, ASE regulated the number of erythrocytes and leucocytes and the hemoglobin content. In addition, the histopathological damage was reduced after treatment with ASE. Moreover, the oxidant and the antioxidant markers (glutathione, malondialdehyde and catalase) were regulated in the infected-treated animals. Collectively, the results proved the protective role of ASE against T. evansi infection in mice.