Even one dose of tocilizumab could hinder bad prognosis of cytokines storm in COVID-19 patients.

Severe COVID-19 pneumonia is a principal cause of death due to cascade of hyper inflammatory condition that leading to lung damage. Therefore, an effective therapy to countercurrent the surge of uncontrolled inflammation is mandatory to propose. Anti-interlukin-6 receptor antagonist monoclonal therapy, tocilizumab (TCZ) showed potential results in COVID-19 patients. This study aimed to emphasize the factors associated with mortality in COVID-19 patients that treated with tocilizumab and may influence the level of serum IL-6. A retrospective cohort study included all patients with clinical parameters that pointed to presence of cytokines storm and treated with one or more doses of TCZ beside the regular protocol of COVID-19 pneumonia. The factors that influence the mortality in addition to the level of serum IL-6 were analyzed. A total of 377 patients were included, 69.5 % of them received only one dose of TCZ which started mainly at the third day of admission. The mortality rate was 29.44 %. Regardless the time of starting TCZ, just one dose was fair enough to prevent bad consequence; OR = 0.04, P = 0.001.However, in spite of protective action of TCZ, older age and female sex were significant risk factors for mortality, P = 0.001 and 0.01 respectively, as well heart disease. Moreover, increasing the level of neutrophil, AST and IL-6 were associated with bad prognosis. In the same line, treatment with ivermectin, chloroquine and remdesivir inversely affect the level of IL-6. Early treatments of COVID-19 pneumonia with at least one dose of tocilizumab minimized the fatality rate.

Histopathological effects of the fruit extract of Citrullus colocynthis on the ovary of the tick Hyalomma dromedarii.

Hyalomma dromedarii is the predominant tick species parasitizing camels in Egypt which leads to mortalities in young animals that result in economic losses. It can transmit a lot of pathogens to animals and humans, such as the Crimean-Congo hemorrhagic fever virus, the Dhori virus, Kadam virus, Theileria annulata and spotted fever rickettsia. The continuous use of chemical acaricides has negative impact on the environment and almost led to acaricidal resistance, and hence the plant extracts represent alternative methods for controlling ticks. The present study was carried out to assess the histopathological effects on the ovary of fed female Hyalomma dromedarii following immersion in the ethanolic extract of fruits of Citrullus colocynthis (100 mg/mL). Light, scanning and transmission electron microscopy observations provided evidence that Citrullus colocynthis caused extensive damage to oocytes. Destruction of the internal organelles of oocytes, along with delay and/or inhibition of vitellogenesis were demonstrated. This is the first histological study that points to damage in H. dromedarii ovaries following treatment with the ethanolic extract of fruits of C. colocynthis. The data presented suggest that the plant extract affects the ovary either directly by entering the oocytes and/or indirectly by damaging the gut cells and digestion of blood that interfere with the development of oocytes, so it can be used as a promising agent for tick control.

Knowledge, Perceptions and Attitude of Researchers Towards Using ChatGPT in Research.

INTRODUCTION: ChatGPT, a recently released chatbot from OpenAI, has found applications in various aspects of life, including academic research. This study investigated the knowledge, perceptions, and attitudes of researchers towards using ChatGPT and other chatbots in academic research. METHODS: A pre-designed, self-administered survey using Google Forms was employed to conduct the study. The questionnaire assessed participants' knowledge of ChatGPT and other chatbots, their awareness of current chatbot and artificial intelligence (AI) applications, and their attitudes towards ChatGPT and its potential research uses. RESULTS: Two hundred researchers participated in the survey. A majority were female (57.5%), and over two-thirds belonged to the medical field (68%). While 67% had heard of ChatGPT, only 11.5% had employed it in their research, primarily for rephrasing paragraphs and finding references. Interestingly, over one-third supported the notion of listing ChatGPT as an author in scientific publications. Concerns emerged regarding AI's potential to automate researcher tasks, particularly in language editing, statistics, and data analysis. Additionally, roughly half expressed ethical concerns about using AI applications in scientific research. CONCLUSION: The increasing use of chatbots in academic research necessitates thoughtful regulation that balances potential benefits with inherent limitations and potential risks. Chatbots should not be considered authors of scientific publications but rather assistants to researchers during manuscript preparation and review. Researchers should be equipped with proper training to utilize chatbots and other AI tools effectively and ethically.

Factors influencing poor response to type 2 targeted therapies in severe asthma: a retrospective cohort study.

BACKGROUND: A significant breakthrough has been made in treating severe asthma, with the recognition of various asthma phenotypes and an updated management guideline. Type 2 targeted therapies, such as benralizumab and omalizumab; have been identified as an effective treatment for severe asthma, improving patient response, lung function tests and asthma symptom control. This study aimed to evaluate factors contributing to poor response to therapy. METHODS: A retrospective single-center cohort study of 162 patients with severe asthma who started biologic therapy; their data were retrieved from medical records for further analysis. Poor responders were patients remained clinically and functionally uncontrolled despite even after augmenting all treatment options. RESULTS: Childhood-onset asthma, bronchiectasis, poor symptom control (ACT below 19), severe airway obstruction (< 60% predicted), and maintenance oral corticosteroid (mOCS) use were significantly associated with poor response to omalizumab and benralizumab; p = 0.0.4 and 0.01; 0.003 and 0.01; 0.01 and 0.001, 0.05 and 0.04; 0.006 and 0.02, respectively. However, chronic rhinosinusitis and IgE < 220kIU/L were associated with higher poor response rates to omalizumab (p = 0.01 and 0.04, respectively). At the same time, female patients and those with blood eosinophils level < 500 cells/mm3 had a higher poor response rate to benralizumab (p = 0.02 and 0.01, respectively). Ischemic heart disease (IHD), bronchiectasis, and continued use of OCS increased the likelihood of poor response to omalizumab by 21, 7, and 24 times (p = 0.004, 0.008, and 0.004, respectively). In contrast, the female gender, childhood-onset asthma and higher BMI increased the likelihood of poor response to benralizumab by 7, 7 and 2 times more, p = 0.03, 0.02 and 0.05, respectively. CONCLUSION: Poor response to omalizumab treatment was independently associated with ischemic heart disease (IHD), bronchiectasis, and a history of maintenance oral corticosteroid (mOCS) use. Conversely, poor response to benralizumab therapy was independently linked to female gender, childhood-onset asthma and higher body mass index (BMI).

Comorbid asthma in patients with chronic rhinosinusitis with nasal polyps: did dupilumab make a difference?

BACKGROUND: The clinical heterogeneity of chronic rhinosinusitis (CRS) and bronchial asthma is attributable to different underlying inflammatory profiles. However, the similarity between CRS with nasal polyps (CRSwNP) and type-2 asthma pathophysiology speculates that one biological therapy could affect both comorbidities. Despite dupilumab, a monoclonal antibody that targets IL-4α and IL-13 receptors, being used in patients with nasal polyps and severe asthma, real-life data about its efficacy in improving the quality of life and patient symptoms is still lacking. This study's primary objective was to evaluate dupilumab treatment's effect on the frequency of olfactory symptoms and health-related quality of life tests as measured by the Sino-nasal outcome test (SNOT-22) in patients with NP. The secondary objective was the effect of dupilumab on asthma symptom control as measured by the asthma control test (ACT). METHODS: A prospective study was conducted of 166 patients with CRSwNP, with or without asthma. The following variables were collected at baseline and after at least six months of continuous dupilumab therapy; SNOT-22, olfactory symptoms frequency, and ACT score. RESULTS: Asthma prevalence in patients with CRSwNP was high (59.63%), and being female with a history of frequent use of oral corticosteroid (OCS) courses and repeated unsuccessful nasal and para-nasal surgeries for polyposis increased the likelihood of having underlying asthma by 2, 1 and 4 times more, respectively. Additionally, being asthmatic required a longer duration of dupilumab treatment. However, both the health-related quality of life and olfactory symptoms improved equally in both groups. CONCLUSION: Even with associated comorbid asthma in patients with CRSwNP, treatment with dupilumab could improve the quality of life, olfactory symptoms, and asthma symptom control.

Elevation of D-dimer levels are associated with early need for mechanical ventilation support in patients with COVID-19.

BACKGROUND: Severe COVID-19 disease is typically associated with an urgent need for supplemental oxygen therapy that may be successfully delivered through conventional methods or require invasive mechanical ventilation. Early prediction of the need for invasive mechanical ventilation could significantly improve outcomes of COVID-19 patients. Plasma levels of D-dimer and a number of inflammatory markers as well as values of complete blood counts, all measured in the first two days of hospital admission of COVID-19 patients, were evaluated for their significance as predictors of the eventual need for invasive mechanical ventilation support as well as their values as predictors of post-ventilation morbidly and mortality. METHODS: This retrospective cohort study was conducted at a single center and included data pertaining to 200 patients with previously confirmed moderate to severe COVID-19 disease in the period between May 2021 and the end of December 2022. Data were retrieved from medical records for further analysis. RESULTS: The mean (SD) age of patients stood at 59 (14) years of age, and with a majority of patients being male (77%). About 18% of cases, all of significantly older age, had been connected to invasive mechanical ventilation (IMV). Total leucocytic count (TLC), as well as levels of urea, creatinine, D-dimer, ferritin, and CRP in IMV patients were significantly higher than non-ventilated patients (p < 0.01 for all). In contrast, lymphocytic count, hemoglobin level, and platelet count were significantly lower in IMV patients (p < 0.001, 0.04, and 0.002, respectively). The mortality rate was significantly higher in IMV patients (p < 0.001). D-dimer independently predicted IMV demand (OR = 1, p = 0.001 in adjusted and unadjusted models). The utility of D-dimer was excellent; and the cutoff level of above 1415 µ/L showed sensitivity and specificity of about 92% and 76%, respectively. Also, the D-dimer level was very effective in predicting post-IMV survival; the AUC = 0.86, p = 0.02, and a cutoff value below 4558 µ/L was associated with 100% and 66% sensitivity and specificity, respectively. CONCLUSIONS: High D-dimer levels independently correlated with the need for invasive mechanical ventilation. Low levels of this marker could evidently predict post-IMV survival of mechanically ventilated COVID-19 patients. Measuring D-dimer levels during routine follow up of those patients would thus be useful in predicting patient outcomes.

Right ventricular systolic function and mechanical dyssynchrony in ischemic or non-ischemic dilated cardiomyopathy: A speckle-tracking study.

AIM: This study assessed RV dyssynchrony (irrespective to QRS duration) and RV systolic function in non-ischemic dilated cardiomyopathy (NIDCM) versus ischemic dilated cardiomyopathy (IDCM) patients by using different echo-Doppler modalities. METHODS: Eighty-five cases (48 patients with DCM [whether ischemic or non-ischemic] and 37 age-matched healthy controls) were studied. Conventional echo-Doppler study, tissue Doppler (TDI), and speckle tracking (STE) were carried out to measure LV and RV systolic function. Time-to-peak negative longitudinal strain at the four RV sites were assessed by TDI derived strain and 2D speckle tracking. RESULTS: Patients with DCM (whether ischemic or non-ischemic) had significantly lower fractional area change, RV tricuspid annular systolic velocity (p < .001 for both), tricuspid annular plane systolic excursion (p = .01), RV-GLS whether TDI or 2D derived (p < .001). Twenty-nine patients (60%) showed right intraventricular delay (RV4SD > 60 ms). The RV-dyssynchrony index was negatively correlated to %FAC (r = -.362, p = .01), RV Sm (r = -.312, p = .04), and 2D-RV GLS (r = -.305, p = .05). Insignificant higher RV-dysynchrony index was detected in NIDCM compared to IDCM group; however, the basal septal segment was significantly delayed in dilated group. More impaired RV systolic function was detected in ischemic group. 2D STE and TDI showed a significant correlation in the assessment of the right-intraventricular delay (p = .001). CONCLUSION: Right-intraventricular dyssynchrony are detectable in patients with dilated cardiomyopathy (whether ischemic or non-ischemic) with a higher statistically insignificant value in non-ischemic group by using tissue Doppler imaging and 2D speckle tracking. More impairment of the RV systolic function was noticed in the ischemic group. Impaired RV systolic function was associated with right intraventricular delay.

Omalizumab Transitions in Severe Asthma: Factors Influencing Switching Decisions and Timing for Optimal Response.

OBJECTIVE: The objective of this study was to assess the effectiveness of switching from omalizumab to another biologic therapy for patients with severe asthma and evaluate factors that influenced the decision to switch and determined the optimal time for a good biologic response. SUBJECTS AND METHODS: A retrospective study of severe asthma patients was conducted at Al-Rashed Allergy Center, a tertiary center in Kuwait. After meeting the eligibility criteria, patients were divided into two comparative groups: those continuing with omalizumab and those who started with omalizumab but switched to another biologic. RESULTS: One hundred sixteen patients with severe asthma were recruited, and only 33 had access to multiple biological treatments. Approximately 22.4% switched from omalizumab. Male patients with a history of ischemic heart disease, chronic rhinosinusitis, and nasal polyps were more likely to switch if they had higher levels of eosinophils in the sputum. This study showed that every 1% increase in sputum eosinophils doubled the likelihood of a switch. Patients with access to alternative biological options had a much shorter mean duration of omalizumab therapy before switching compared to those with only affordable omalizumab: 4.9 ± 1.5 years versus 8.9 ± 1.3 years (p < 0.001). The optimal time to predict the likelihood of a good response was less than 5.5 years, with an area under the curve of 0.91 and p = 0.003. This cutoff point provided a sensitivity and specificity of approximately 89% and 100%, respectively. CONCLUSION: An early transition from omalizumab, specifically within the first 5 years of treatment, in patients with severe asthma and higher sputum eosinophils may enhance the likelihood of a good response if other biological therapies were available.

Evaluation of the interaction between anti-apoptotic Bcl-2 protein family mRNA expression and autophagy gene Bcl-1 expression in Egyptian SLE patients.

OBJECTIVES: Autophagy is a complex cellular process that maintains homeostasis in systemic lupus erythematosus. Abnormally high expression of Bcl-2 was observed in B and T lymphocytes in the peripheral blood in SLE patients. These may be responsible for the survival of self-reactive lymphocytes and the development of lupus, and the study aims at evaluating interaction between apoptosis and autophagy in Egyptian lupus patients. METHODS: Sixty patients with SLE were diagnosed by fulfilling the Systemic Lupus International Collaborating Clinics (SLICC) classification criteria for SLE and sixty healthy age and sex matched control. All patients were subjected to full medical history and clinical examination. Activity was assessed using SLEDAI-2K score. Gene expression of Beclin-1, Bcl-2-L2, and Bcl-2 was measured. RESULTS: The study revealed that the expression of anti-apoptotic Bcl-2 and Bcl-2-L2 was significantly higher in SLE patients than control subjects, as well as the major apoptotic agent (Beclin-1) mRNA, p = 0.03, < 0.001 and 0.02, respectively. The apoptotic Beclin-1 mRNA was positively correlated with SLE disease severity index, r = 0.25; p = 0.0.4; therefore, our results showed that expression of the Beclin-1 was significantly higher in SLE patients than control (p < 0.02). CONCLUSION: Our results showed that expression of the Beclin 1 were significantly higher in SLE patients than control (p < 0.02).

Optimization and SAR investigation of novel 2,3-dihydropyrazino[1,2-a]indole-1,4-dione derivatives as EGFR and BRAFV600E dual inhibitors with potent antiproliferative and antioxidant activities.

Using a single drug to treat cancer with dual-targeting is an unusual approach when compared to other drug combinations. Dual-targeting agents were developed as a result of insufficient efficacy and drug resistance when single-targeting agents were used. As a result, the 2,3-dihydropyrazino[1,2-a]indole-1,4-dione derivatives 13-22 have been developed as dual EGFR and BRAFV600E inhibitors. The target compounds were synthesized and tested in vitro against four cancer cell lines, with compounds 15, and 19-22 demonstrating potent antiproliferative activity. In vitro studies revealed that these compounds have dual inhibitory effect on EGFR and BRAFV600E. Compounds 15, and 19-22 exhibited inhibitions of EGFR with IC50 ranging from 32 nM to 63 nM which were superior to erlotinib (IC50 = 80 ± 10 nM). Compounds 20, 21 and 22 showed promising inhibitory activity of BRAFV600E (IC50 = 55, 45 and 51 nM, respectively) and were found to be potent inhibitors of cancer cell proliferation (GI50 = 51, 35 and 44 nM, respectively). Compounds 20, 21 and 22 showed good antioxidant activity comparable to the reference Trolox. Lastly, the best active dual inhibitors were docked inside EGFR and BRAFV600E active sites to clarify their binding modes.

Lactobacillus rhamnosus TR08 Improves Dyslipidemia in Mice Fed with a High Fat Diet by Regulating the Intestinal Microbiota, Reducing Systemic Inflammatory Response, and Promoting Sphingomholipid Metabolism.

Dysbiosis is a crucial manifestation of dyslipidemia; however, oral supplementation of probiotic modulates the intestinal commensal composition. The protective mechanism of probiotics against hyperlipidemia is still under investigation. To elucidate the hypolipidemic effect of Lactobacillus rhamnosus TR08 through the analysis of gut microbiota and lipid metabolomics, we investigated changes in gut microbiota and lipid metabolomic phenotypes in mice by real time quantitative PCR and untargeted metabolomics analysis. High fat diet-induced dyslipidemia mice were orally administered with TR08 for 8 weeks. The proinflammatory cytokines (interleukin-2 and interferon-γ) levels in spleen and aortic wall injury in the mice fed with a high-fat diet were inhibited after treatment with TR08 at 1 × 108 CFU per day per mouse. TR08 also reshaped the gut microbiota with increases of the relative abundances of Bifidobacterium and Bacteroides, reduced the abundance of the pro-pathogen bacterial Enterococcus, increased the serum level of short chain fatty acids (SCFAs) contents, and promoted sphingomholipid metabolic pathway. The results indicated that TR08 could improve the intestinal microbiota of mice to increase the production of SCFAs, and then play the anti-inflammation induced by hyperlipidemia and reduce the inflammatory injury of blood vessel wall. Therefore, TR08 can potentially be used as a hypolipidemic effect probiotic in further interventions.

In vivo evidence of lumbricals incursion into the carpal tunnel in healthy hands: An ultrasonographic cross sectional study.

INTRODUCTION: During finger flexion, the tendons of flexor digitorum profundus migrate proximally, along with their attached lumbrical muscles. This incursion was suggested to extend into the Carpal Tunnel. Ultrasonographic imaging can be used to assess in vivo soft tissue behavior and incursion. PURPOSE OF THE STUDY: To clinically quantify the lumbrical muscles incursion in different finger positions. STUDY DESIGN: Cross sectional, observational study. METHODS: The lumbricals of 20 healthy adults with no history of hand injuries were evaluated with neuromuscular ultrasound imaging (n = 160 lumbricals). The lumbrical muscles migration was measured as the participants actively moved their fingers from full extension to 50% flexion, and 100% flexion. RESULTS: Of the 160 lumbricals measures, the incursion occurred at 18.1% of fingers at 50% finger flexion, and increased to 79.4% during full finger flexion. The lumbricals migrated a total of 2.99 cm after full finger flexion, and ended up 0.76 cm (SD = 0.86 cm) inside the Carpal Tunnel. The metacarpophalangeal joint range of motion of the index finger at the point where the lumbricals entered the distal border of the Transverse Carpal Ligament was 84.4° (SD = 6.8°). The Carpal Tunnel cross-sectional area during finger extension was 1.68 (0.35) cm2, and increased to 1.81 (0.33) cm2 after full finger flexion. CONCLUSION: This study showed direct evidence of lumbrical incursion into the Carpal Tunnel during finger flexion. The cross-sectional area of the Carpal Tunnel increased during full finger flexion in comparison to full finger extension, supplementing the evidence of increase content within the Carpal Tunnel. The findings of this study have significant clinical implications for the conservative treatment of the Capral Tunnel Syndrome.

Design, synthesis, and biological evaluation of novel EGFR inhibitors containing 5-chloro-3-hydroxymethyl-indole-2-carboxamide scaffold with apoptotic antiproliferative activity.

New EGFR inhibitor series of fifteen 5-chloro-3-hydroxymethyl-indole-2-carboxamide derivatives has been designed, synthesized, and tested for antiproliferative activity against a panel of cancer cell lines. The results showed that p-substituted phenethyl derivatives 10, 11, 13, 15 and 17-19 showed superior antiproliferative activity compared to their m-substituted counterparts 12, 14, 16 and 20. Compounds 15, 16, 19 and 20 displayed promising EGFR inhibitory activity as well as an increase in caspase 3 levels. Compounds 15 and 19 increased caspase-8 and 9 levels, as well as inducing Bax and decreasing Bcl-2 protein levels. Compound 19 demonstrated cell cycle arrest at pre-G1 and G2/M phases. The results of the docking study into the active site of EGFR revealed strong fitting of the new compounds with higher binding affinities compared to erlotinib.

Cold-pressed raspberry seeds oil ameliorates high-fat diet triggered non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is considered one of the most serious public health problems affecting liver. The reported beneficial impact of raspberries on obesity and associated metabolic disorder makes it a suitable candidate against NAFLD. In the current study, the chemical profile of raspberry seed oil (RO) was characterized by analysis of fatty acid and tocopherol contents using high-performance liquid chromatography (HPLC) in addition to the determination of total phenolic and flavonoids. High levels of unsaturated fatty acids, linoleic acid (49.9%), α-linolenic acid (25.98%), and oleic acid (17.6%), along with high total tocopherol content (184 mg/100 gm) were detected in oil. The total phenolic and flavonoid contents in RO were estimated to be 22.40 ± 0.25 mg gallic acid equivalent (GAE)/100 mg oil and 1.34 ± 0.15 mg quercetin (QU)/100 mg, respectively. Anti-NAFLD efficacy of RO at different doses (0.4 and 0.8 mL) in a model of a high-fat diet (HFD) fed rats was assessed by estimating lipid profile, liver enzyme activity, glucose and insulin levels as well as adipokines and inflammatory marker. Peroxisome proliferator-activated receptor γ (PPARγ), which is a molecular target for NAFLD was also tested. Liver histopathology was carried out and its homogenate was used to estimate oxidative stress markers. Consumption of RO significantly improved lipid parameters and hepatic enzyme activities, reduced insulin resistance and glucose levels, significantly ameliorated inflammatory and oxidative stress markers. Furthermore, RO treatment significantly modulated adipokines activities and elevated PPARγ levels. Raspberry seed oil administration significantly improved these HFD induced histopathological alterations. Moreover, a molecular docking study was performed on the identified fatty acids and tocopherols. Among the identified compounds, oleic acid, α-linolenic acid and γ-tocopherol exhibited the highest docking score as PPARγ activator posing them as a potential anti-NAFLD drug leads. Study findings suggest RO as an effective therapeutic candidate for ameliorating NAFLD.

Molecular characterization of virulence and drug resistance genes-producing Escherichia coli isolated from chicken meat: Metal oxide nanoparticles as novel antibacterial agents.

Escherichia coli is a major global foodborne pathogen, infecting a wide range of animals and contaminating their meat products. E. coli, can lead to high morbidity and mortality with a huge economic loss especially if foodborne diseases are associated with multidrug resistant (MDR)- and multivirulent-producing pathogens. Due to the increased resistance to common antimicrobials used to treat livestock animals and human infections, the discovery of new and innovative nanomaterials are in high demand. Recently, metal oxides can be considered as effective inorganic agents with antimicrobial features. Hence, this study might be the first to evaluate the efficiency of metal oxide nanoparticles (MO-NPs) as novel antibacterial agents against MDR/multivirulent E. coli pathogens isolated from chicken meat. The occurrence of pathogenic E. coli was determined in fresh warm chicken meat parts (breast, thigh, liver and gizzard). Ninety-one of 132 (69%) chicken meat parts were Escherichia -positive with E. coli as the only species isolated. Out of identified 240 E. coli strains, 72.5% (174/240) were classified as MDR E. coli strains. Fifty-five profile patterns were obtained. From each pattern, one strain was randomly selected for further analysis of virulence and resistance genes. Extracted DNA was assessed for the presence of antibiotic resistance genes (blaIMP-7, blaIMP-25, blaTEM, blaSHV, blaOXA-2, tetA, aadA, and aac(3)-IV) and virulence genes (stx1, stx2, hlyA, eaeA, aggR, eltB, estIb, papA, afa and hlyD). Clustering analyses revealed that 10 E. coli harboring the highest number of virulence and resistance genes were shifted together into one cluster designated as cluster X. The average activities of zinc peroxide nanoparticles (ZnO2-NPs) were higher than that of zinc oxide nanoparticles (ZnO-NPs) and titanium dioxide nanoparticles (TiO2-NPs) by 20% and 29%, respectively. The anti-inflammatory activity of ZnO2-NPs in comparison with aspirin was assessed using membrane stabilization, albumin denaturation, and proteinase inhibition methods. Significant anti-inflammatory activity of ZnO2-NPs was achieved at concentration levels of 500-1000 µg/ml. It seems that MO-NPs are effective alternative agents, since they exhibited a competitive antibacterial capability against MDR/multivirulent-producing E. coli pathogens isolated from chicken meat. Hence, ZnO2-NPs are a promising nanoparticles-based material for controlling foodborne pathogens, thereby valued for food safety applications.

Novel class of benzimidazole-thiazole hybrids: The privileged scaffolds of potent anti-inflammatory activity with dual inhibition of cyclooxygenase and 15-lipoxygenase enzymes.

The present study includes design and synthesis of new molecular hybrids of 2-methylthiobenzimidazole linked to various anti-inflammatory pharmacophores through 2-aminothiazole linker, to investigate the effect of such molecular variation on cyclooxygenase (COX) and 15-lipoxygenase (15-LOX) enzymes inhibition as well as in vivo anti-inflammatory activity. The chemical structures of new hybrids were confirmed using different spectroscopic tools and elemental analyses. Benzimidazole-thiazole hybrids linked to acetyl moiety 13, phenyl thiosemicarbazone 14, 1,3-thiazolines 15a-c and 4-thiazolidinone 16 exhibited significant COX-2 inhibition (IC50 = 0.045-0.075 µM) with significant COX-2 selectivity indices (SI = 142-294). All hybrids revealed potent 15-LOX inhibitory activity (IC50 = 1.67-6.56 µM). Benzimidazole-thiazole hybrid 15b was the most potent dual COX-2 (IC50 = 0.045 µM, SI = 294) inhibitor approximate to celecoxib (COX-2; IC50 = 0.045 µM, SI = 327), with double inhibitory activity versus 15-LOX enzyme (IC50 = 1.67 µM) relative to quercetin (IC50 = 3.34 µM). Three hybrids (14, 15b &16) were selected for in vivo screening using carrageenan-induced paw edema method. Benzimidazole-thiazole hybrid linked to 4-thiazolidinone 16 showed the maximum edema inhibition at both 3 h and 4 h intervals as well (~119% and 102% relative to indomethacin, respectively). The gastric ulcerogenic effect of benzimidazole-thiazole hybrid 16 was estimated compared with indomethacin showing superior gastrointestinal safety profile. In bases of molecular modeling; all new active hybrids were subjected to docking simulation into active sites of COX-2 and 15-LOX enzymes to study the binding mode of these novel potent dual COX-2/15-LOX inhibitors.

Design and synthesis of novel 2,3-dihydropyrazino[1,2-a]indole-1,4-dione derivatives as antiproliferative EGFR and BRAFV600E dual inhibitors.

Recent studies have shown additive and synergistic effects associated with the combination of kinase inhibitors. BRAFV600E and EGFR are attractive targets for many diseases treatments and have been studied extensively. In keeping with our interest in developing anticancer targeting EGFR and BRAFV600E, a novel series of 2,3-dihydropyrazino[1,2-a]indole-1,4-dione has been rationally designed, synthesized and evaluated for their antiproliferative activity against a panel of four human cancer cell lines. Compounds 20-23, 28-31, and 33 showed promising antiproliferative activities. These compounds were further tested for their inhibitory potencies against EGFR and BRAFV600E kinases with erlotinib as a reference drug. Compounds 23 and 33 exhibited equipotency to doxorubicin against the four cell lines and efficiently inhibited both EGFR (IC50 = 0.08 and 0.09 µM, respectively) and BRAFV600E (IC50 = 0.1 and 0.29 µM, respectively). In cell cycle study of MCF-7 cell line, compounds 23 and 33 induced apoptosis and exhibited cell cycle arrest in both Pre-G1 and G2/M phases. Molecular docking analyses revealed that the new compounds can fit snugly into the active sites of EGFR, and BRAFV600E kinases. Compound 23, 31 and 33 adopted similar binding orientations and interactions to those of erlotinib and vemurafenib.

Disjoint Spanning Tree Based Reliability Evaluation of Wireless Sensor Network.

Wireless sensor networks (WSNs) are becoming very common in numerous manufacturing industries; especially where it is difficult to connect a sensor to a sink. This is an evolving issue for researchers attempting to contribute to the proliferation of WSNs. Monitoring a WSN depends on the type of collective data the sensor nodes have acquired. It is necessary to quantify the performance of these networks with the help of network reliability measures to ensure the stable operation of WSNs. Reliability plays a key role in the efficacy of any large-scale application of WSNs. The communication reliability in a wireless sensor network is an influential parameter for enhancing network performance for secure, desirable, and successful communication. The reliability of WSNs must incorporate the design variables, coverage, lifetime, and connectivity into consideration; however, connectivity is the most important factor, especially in a harsh environment on a large scale. The proposed algorithm is a one-step approach, which starts with the recognition of a specific spanning tree only. It utilizes all other disjoint spanning trees, which are generated directly in a simple manner and consume less computation time and memory. A binary decision illustration is presented for the enumeration of K-coverage communication reliability. In this paper, the issue of computing minimum spanning trees was addressed and it is a pertinent method for further evaluating reliability for WSNs. This paper inspects the reliability of WSNs and proposes a method for evaluating the flow-oriented reliability of WSNs. Further, a modified approach for the sum-of-disjoint products to determine the reliability of WSN from the enumerated minimal spanning trees is proposed. The proposed algorithm when implemented for different sizes of WSNs demonstrates its applicability to WSNs of various scales. The proposed methodology is less complex and more efficient in terms of reliability.

Drug resistance profile and molecular characterization of extended spectrum beta-lactamase (ESßL)-producing Pseudomonas aeruginosa isolated from burn wound infections. Essential oils and their potential for utilization.

OBJECTIVES: Pseudomonas aeruginosa producing extended spectrum ß-lactamase (ESßL) enzyme had the ability for antimicrobial resistance mechanisms and its multidrug-resistant (MDR) phenotype, has been increasingly reported as a major clinical concern worldwide. The aim of this study was to (i) characterize ESßL-producing MDR P. aeruginosa isolated from burn wound infections phenotypically and molecularly, (ii) evaluate the antibacterial activity of some essential oils (EOs) against selected ESßL-producing drug resistant P. aeruginosa and (iii) characterize a promising EO. METHODS: Identification and antibiotic susceptibility tests were performed for all isolates. ESßL production was detected phenotypically by an initial screening test (IST) and a phenotypic confirmatory test (PCT). Additionally, ESßL-producing isolates were also characterized molecularly. The antibacterial activity was detected using a disc diffusion method. Mechanisms of antibacterial action, the fatty acid profile, and functional groups characterization of the promising EO were analyzed using scanning and transmission electron microscopy (SEM & TEM), gas chromatography-mass spectrometry (GC-MS), and Fourier transform infrared (FTIR) spectroscopy, respectively. RESULTS: A total of 50 non duplicated P. aeruginosa isolates from the wound samples of burn patients were identified. Of these, MDR and pan-drug resistance (PDR) showed a high prevalence in 38 (76%) isolates obtained from 10 clusters, while 21 (42%) were identified as ESßL-producing MDR or PDR P. aeruginosa isolates. Phenotypic detection of ESßL production showed that 20% were considered positive ESßL-producing P. aeruginosa using the IST, and were increased to 56% by the PCT. The most prevalent ESßL-encoding gene was blaOXA-2 (60.7%), followed by blaIMP-7 (53.6%) and blaOXA-50 (42.8%). Ginger oil is the most efficient antibacterial agent and its antibacterial action mechanism is attributed to the morphological changes in bacterial cells. The oil characterization revealed that 9,12-Octadecadienoic acid methyl ester is the major fatty acid (50.49%) identified. CONCLUSION: The high incidence of drug-resistance in ESßL-producing P. aeruginosa isolated from burn wounds is alarming. As proven in vitro, EOs may represent promising natural alternatives against ESßL-producing PDR or MDR P. aeruginosa isolates.

Pharmaceutical Potential of a Novel Chitosan Derivative Schiff Base with Special Reference to Antibacterial, Anti-Biofilm, Antioxidant, Anti-Inflammatory, Hemocompatibility and Cytotoxic Activities.

PURPOSE: Chitosan and its derivatives possess several unique properties relevant in the field of pharmaceutics and medicinal chemistry. This study aimed to evaluate the pharmaceutical performance of an innovative chitosan derivative, methyl acrylate chitosan bearing p-nitrobenzaldehyde (MA*CS*pNBA) Schiff base. METHODS: The antibacterial activity of MA*CS*pNBA was tested against multi-drug resistant (MDR) Gram-negative and Gram-positive bacteria using agar-well diffusion method. Anti-biofilm formation was analyzed using a microtitre plate. Antioxidant assays were performed to assess the scavenging activity of MA*CS*pNBA using DPPH, hydrogen peroxide, superoxide together with its reducing power activity. Anti-inflammatory activity was evaluated by albumin denaturation, membrane stabilization, and proteinase inhibition methods. MA*CS*pNBA was tested for its hemolytic efficiency on human erythrocytes. Cytotoxicity of MA*CS*pNBA was evaluated by MTT assay. RESULTS: MA*CS*pNBA showed a significant performance as an antibacterial candidate against MDR bacteria, anti-biofilm, antioxidant and anti-inflammatory biomaterial, evidencing hemocompatibility and no cytotoxicity. It exhibited a significant negative correlation with biofilm formation by the MDR-PA-09 strain. Biological activities were found to be significantly concentration-dependent. CONCLUSIONS: the newly chitosan derivative MA*CS*pNBA showed to be promising for pharmaceutical applications, expanding the treatment ways toward skin burn infections since it allied excellent antibacterial, anti-biofilm, antioxidant, anti-inflammatory, hemocompatibility and absence of cytotoxic activities.