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Rationale, Aims and Objectives Method Results Conclusion Diabetes mellitus is a global serious health problem that has a clear negative impact on economy. The high prevalence of diabetes worldwide urges for prevention and educational programs. Engagement of community pharmacists in offering various diabetes care services enables delivery of quality of care for patients and could play key role in diabetes management. The current study was designed to assess the knowledge towards diabetes among community pharmacists and to investigate their role in diabetes management through identifying different diabetes care services they provide in Asir region, Saudi Arabia. In addition, possible barriers for providing these services were evaluated.A cross‐sectional study was performed using an online self‐administered anonymous survey that consisted of 4 domains: demographics, knowledge, practice and barriers related to diabetes management.A total of 258 pharmacists completed the survey, and one‐third of respondents (34.5%) demonstrated good knowledge while 42.2% showed moderate knowledge towards diabetes. Respondents of the age group (30–39) years, males, those with bachelor's degree and those with 5 years or less of experience had higher mean knowledge. Nearly half of the participants had positive practice. The most prominent (75%) services offered by the community pharmacists were counselling on the appropriate administration, handling and storage of insulin and the appropriate time to administer oral antidiabetic drugs. Pharmacists who received training had higher mean practice scores. Lack of time, lack of diabetic patients visiting the pharmacy and low patient expectations regarding pharmacists' role in diabetes care were identified as the most important barriers they encountered.Community pharmacists of Asir region exhibited moderate knowledge and practices regarding diabetes management. Our results support the need for national advanced diabetes training programs targeting community pharmacists for providing quality of care services for diabetic patients Moreover, strategies to overcome the reported barriers are indispensable. [ABSTRACT FROM AUTHOR]

Alzheimer's disease is the most serious neurodegenerative disorder characterized by cognitive and memorial defects alongside deterioration in behavioral, thinking and social skills. Donepezil hydrochloride (DPZ) is one of the current two FDA-approved cholinesterase inhibitors used for the management of Alzheimer's disease. The current study aimed to formulate hyaluronic acid-coated transfersomes containing DPZ (DPZ-HA-TFS) for brain delivery through the intranasal pathway to surpass its oral-correlated GIT side effects. DPZ-HA-TFS were produced using a thin film hydration method and optimized with a 24 factorial design. The influence of formulation parameters on vesicle diameter, entrapment, cumulative release after 8 h, and ex vivo nasal diffusion after 24 h was studied. The optimal formulation was then evaluated for morphology, stability, histopathology and in vivo biodistribution studies. The optimized DPZ-HA-TFS formulation elicited an acceptable vesicle size (227.5 nm) with 75.83% entrapment efficiency, 37.94% cumulative release after 8 h, 547.49 µg/cm2 permeated through nasal mucosa after 24 h and adequate stability. Histopathological analysis revealed that the formulated DPZ-HA-TFS was nontoxic and tolerable for intranasal delivery. Intranasally administered DPZ-HA-TFS manifested significantly superior values for drug targeting index (5.08), drug targeting efficiency (508.25%) and direct nose-to-brain transport percentage (80.32%). DPZ-HA-TFS might be deemed as a promising intranasal nano-cargo for DPZ cerebral delivery to tackle Alzheimer's disease safely, steadily and in a non-invasive long-term pattern. [ABSTRACT FROM AUTHOR]

Introduction: Improper glycemic control is associated with diabetic cognitive dysfunction. Several studies have confirmed the neuroprotective effects of metformin and insulin. This study aimed to investigate the effects of metformin and/or insulin therapy on neurocognitive functions in a type 2 diabetes mellitus (T2DM) rat model. Methods: Fifty adult male Wistar rats were used in this study and had free access to water and a normal chow diet. After an acclimatization period, 10 rats were kept on a normal chow diet and considered as the control group. T2DM was induced in the other 40 rats by a high-fat diet and low-dose streptozotocin method. Then, diabetic rats were randomly allocated into 4 equal groups: Non-treated diabetic group; Metformin-treated diabetic group (treated with metformin 250 mg/kg/day for 6 weeks); Insulin-treated diabetic group (treated with NPH insulin 40 U/kg for 6 weeks); and Metformin and insulin-treated diabetic group. Neurocognitive functions were assessed by footprint assay, Y-maze, open field test, and Morris water maze. Glycaemic profile, serum levels of amyloid A, interleukin-18, and nuclear factor-kappa B were analyzed. Brain malondialdehyde and total antioxidant capacity were measured. A histopathological examination of the frontal lobe was performed. Results: Treatment with metformin and/or insulin significantly improved the impaired neurocognitive dysfunction, brain oxidative stress, changes in biochemical parameters, and the associated histopathological changes in the frontal cortex of diabetic rats. The combined therapy showed a better effect than either monotherapy alone. Conclusion: Metformin and insulin therapy may be valuable for the prevention of neurocognitive dysfunction in T2DM. [ABSTRACT FROM AUTHOR]

In consideration of the chromones' therapeutic potential and anticancer activity, a new series of chromanone derivatives have been synthesized through a straightforward reaction between 6-formyl-7-hydroxy-5-methoxy-2-methylchromone (2) and various organic active compounds. The cytotoxic activity of the newly synthesized congeners was investigated against MCF-7 (human breast cancer), HCT-116 (colon cancer), HepG2 (liver cancer), and normal skin fibroblast cells (BJ1). The obtained data indicated that compounds 14b, 17, and 19 induce cytotoxic activity in the breast MCF7, while compounds 6a, 6b, 11 and 14c showed highly potent activity in the colon cancer cell lines. Overall, the results demonstrate that the potential cytotoxic effects of the studied compounds may be based on their ability to induce DNA fragmentation in cancer cell lines, down-regulate the expression level of CDK4 as well as the anti-apoptotic gene Bcl-2 and up-regulate the expression of the pro-apoptotic genes P53 and Bax. Furthermore, compounds 14b and 14c showed a dual mechanism of action by inducing apoptosis and cell cycle arrest. The docking studies showed that the binding affinity of the most active cytotoxic compounds within the active pocket of the CDK4 enzyme is stronger due to hydrophobic and H-bonding interactions. These results were found to be consistent with the experimental results. [ABSTRACT FROM AUTHOR]

Background A serious issue with world health is tuberculosis (TB). Annual estimates from the World Health Organization (WHO) put the number of incident cases at 9.6 million. The aim of this work was to compare between real-time polymerase chain reaction (PCR) and GeneXpert in recognition of Mycobacterium tuberculosis (MTB) with special reference to quantification of MTB and to speed of detection of the organism. Materials and Methods Thirty individuals participated in this prospective clinical quasi-interventional trial with clinical data and chest radiography suggestive of pulmonary tuberculosis. Participants were split into three groups equally: group I (control group) was zielneilsen stain (ZN) stain positive and culture positive, group II were ZN stain negative and culture positive and group III were ZN stain negative and culture negative. Each participant was exposed to a plain chest radiography and a complete blood picture. Results Real-time PCR result was significantly correlated with loss of appetite and weight in group III. There were negative correlations between PCR and mediastinal lymphadenopathy in group I. In group I GeneXpert was significantly correlated with night sweat and fever, breathlessness and cavitary lesion. In group III GeneXpert was significant correlated with site of lesion and night sweat and fever. Conclusions For TB patients, the PCR test is crucial in order to provide prompt diagnosis and therapy. When comparing AdvanSure tuberculous /non tuberculous mycobacterium (TB/NTM) real-time PCR with Xpert MTB/rifampicin (RIF) assay, the latter is more advantageous due to its test-method simplicity and quicker than real-time PCR ability to simultaneously identify rifampin resistance. However, its sensitivity for specimens with an acid-fast bacilli (AFB) smear negative but a positive culture is less than AdvanSure TB/NTM real-time PCR. With special reference to the quantification of MTB, TB/NTM real-time PCR is a quantitative test but Xpert MTB/ RIF is semiquanitative. [ABSTRACT FROM AUTHOR]

Oilfield scaling is a major problem in the oil and gas industry. Scaling issues cost the industry millions of dollars in damage and lost production every year as scaling is one of the main causes of global production decline. In this study, solid scale inhibitors based on silver tungstate loaded KIT-6 were synthesized and evaluated using a static scale inhibition test. The synthesized materials were characterized using wide and low XRD, N2 adsorption–desorption, TGA, and FTIR, SEM, and XPS analyses. Small-angle XRD patterns showed that KIT-6 had 3D-mesopore diffraction peaks with a cubic Ia3d space group. Wide-angle XRD patterns of silver tungstate loaded KIT-6 confirmed the crystallinity. The prepared catalysts are characterized by higher surface areas (394–918 m2 g−1), large pore volumes (0.63–0.98 cm3 g−1), narrow pore size distributions (5.3 nm), and high thermal stability up to 1000 °C. The results of this study demonstrate that the inhibition efficiency of the scale inhibitor increases and that of the calcite scale inhibitor decreases with increasing pH (2 to 8). This proposes that the scale inhibitor is more effective under alkaline conditions. An inhibition efficiency of 99% on calcium carbonate can be achieved at an optimal dosage of 7.5 ppm at 55 °C, indicating that the scale inhibitor exhibits a relatively good inhibition performance on calcium carbonate. The use of these materials can potentially lead to more efficient and cost-effective solutions for scale inhibition in various industrial processes. [ABSTRACT FROM AUTHOR]

Introduction: Thyroid dysfunction adversely affect the pancreas. Hesperidin, a flavonoid, has been explored for treating pancreatic disorders including diabetes and pancreatitis. Objectives: Evaluation of possible protective effect of hesperidin on pathophysiological and structural pancreatic changes in carbimazole-induced hypothyroidism rat model. Material and Method: Thirty adult male albino rats were divided into 3 groups (I) control, (II) hypothyroid, (III) hypothyroid hesperidin treated group. Finally, rats were sacrificed; blood samples were collected to measure the levels of serum amylase, lipase, insulin and fasting blood glucose. Malondialdehyde (MDA) and antioxidant enzymes were measured in pancreatic homogenate. Pancreatic tissues were used in the histological, electron microscopic, morphometric and immunohistochemical studies for Bax and insulin proteins. Results: Hypothyroid rats showed a significant decrease of serum amylase, lipase and pancreatic antioxidant enzymes compared with control. There was a significant increase of fasting blood glucose, serum insulin, homeostatic model assessment in hypothyroid rats compared with control. There were no significant statistical differences between MDA levels among all groups. Hypothyroid group revealed fatty infiltration and eosinophilic material deposition in the pancreatic connective tissue septa. Acinar cells showed small dark nuclei, increased basal basophilia, cytoplasmic vacuolation, degenerated mitochondria and dilated rough endoplasmic reticulum. β-cells of pancreatic islets were densely packed with insulin granules. There was a significant increase of insulin immune-expression and increased of Bax immunoreactivity. Hypothyroid group displayed a significant decrease of zymogen granules and significant increase in collagen fibers deposition compared with control. Hesperidin administration to hypothyroid rats significantly improved serum amylase, lipase and pancreatic antioxidant enzymes levels, down regulated insulin and Bax immunoexpression. Zymogen granules were significantly increased and collagen fibers were significantly decreased compared with hypothyroid group. Histological results were consistent with the biochemical results. Conclusion: Hesperidin treatment of hypothyroid rats reversed the associated functional and structural pancreatic changes via antioxidant and antiapoptotic mechanisms. [ABSTRACT FROM AUTHOR]

Novel PbMoO4/BiOBr nanocomposites were fabricated via a facile ultrasound-assisted impregnation method. The fabricated nanocomposites were extensively investigated using various techniques such as XRD, FT-IR, BET surface area, Raman, XPS, SEM, and TGA. The catalytic capability of the synthesized materials was investigated for the catalytic oxidative desulfurization (CODS) of actual fuel using a mixture of hydrogen peroxide and acetic acid as an oxidizing agent and acetonitrile as extracting solvent. Reaction time, catalyst dose, temperature, and oxidant and reactant volume were evaluated in detail. The PbMoO4/BiOBr nanocomposite exhibits satisfying catalytic efficiency (98.3%), achieving the goal of ultra-low sulfur content diesel. The results emphasize the newly prepared composite as a real contender at the industrial level under mild conditions. The composite revealed superior stability for four successive reuses without a notable decrease in catalytic performance. The suggested CODS mechanism was investigated. [ABSTRACT FROM AUTHOR]

Aims The objective of this study was to retrospectively evaluate the incidence, management, and outcome of occult pneumothorax (OPTX) in patients with blunt chest trauma (BCT). Settings and design A retrospective observational study was performed. Patients and methods Over 9 years, cases with BCT were identified retrospectively from the database between 2012 and 2021. Data were evaluated and compared based on the first management (conservative vs. intercostal tube). Results Of the 2113 cases, 51 (2.4%) admitted with BCT during the study period were found to have OPTX. The mean age of patients was 37 ± 6.58 years, and there was a male predominance (78.43%). Intercostal tube intervention was done in 29 (53.8%) cases, and conservative management was done in 22 (43.13%) cases. Cases that needed tube thoracostomy had significantly higher rates of lung and chest contusions and high Abbreviated Injury Scale compared with those who were treated conservatively. However, pneumonia, rib fracture, hospital length of stay, and ventilatory days were insignificantly different between both groups. Overall mortality was 9.8%. Conclusions In cases with BCT that did not require major interventions or needed to be mechanically ventilated, their OPTX can be safely managed conservatively. [ABSTRACT FROM AUTHOR]

There has been a rapid increase in the world's output of main poultry products (meat and eggs). This reflects customer desire for these high‐quality and safe products and the comparatively low price. Recently, natural feed additives, plants and products have been increasingly popular in the poultry and livestock industries to maintain and improve their health and production. Polyphenols are a type of micronutrient that is plentiful in our diet. They are phytochemicals that have health benefits, notably cardiovascular, cognitive function, antioxidant, anti‐mutagenic, anti‐inflammatory, antistress, anti‐tumour, anti‐pathogen, detoxification, growth‐promoting and immunomodulating activities. On the other hand, excessive polyphenol levels have an unclear and sometimes negative impact on gastrointestinal tract health, nutrient digestion, digestive enzyme activity, vitamin, mineral absorption, laying hens performance and egg quality. As a result, this review illuminated polyphenols' various sources, classifications, biological activities, potential usage restrictions and effects on poultry, layer productivity and egg external and internal quality. [ABSTRACT FROM AUTHOR]

Budesonide (BUD), a glucocorticoids drug, inhibits all steps in the inflammatory response. It can reduce and treat inflammation and other symptoms associated with acute lung injury such as COVID-19. Loading BUD into bilosomes could boost its therapeutic activity, and lessen its frequent administration and side effects. Different bilosomal formulations were prepared where the independent variables were lipid type (Cholesterol, Phospholipon 80H, L-alpha phosphatidylcholine, and Lipoid S45), bile salt type (Na cholate and Na deoxycholate), and drug concentration (10, 20 mg). The measured responses were: vesicle size, entrapment efficiency, and release efficiency. One optimum formulation (composed of cholesterol, Na cholate, and 10 mg of BUD) was selected and investigated for its anti-inflammatory efficacy in vivo using Wistar albino male rats. Randomly allocated rats were distributed into four groups: The first: normal control group and received intranasal saline, the second one acted as the acute lung injury model received intranasal single dose of 2 mg/kg potassium dichromate (PD). Whereas the third and fourth groups received the market product (Pulmicort® nebulising suspension 0.5 mg/ml) and the optimized formulation (0.5 mg/kg; intranasal) for 7 days after PD instillation, respectively. Results showed that the optimized formulation decreased the pro-inflammatory cytokines TNF-α, and TGF-β contents as well as reduced PKC content in lung. These findings suggest the potentiality of BUD-loaded bilosomes for the treatment of acute lung injury with the ability of inhibiting the pro-inflammatory cytokines induced COVID-19. [ABSTRACT FROM AUTHOR]

Duloxetine HCl (DXH) is a psychiatric medicine employed for treating major depressive disorder. Nonetheless, its low water solubility, high first-pass metabolism, and acid instability diminish the absolute oral bioavailability to 40%, thus necessitating frequent administration. Therefore, the aim of the current study was to formulate DXH as nasal chitosan-grafted polymeric nanoparticles to improve its pharmacokinetic and pharmacodynamic properties. Applying the Box-Behnken design, DXH loaded PLGA-Chitosan nanoparticles (DXH-PLGA-CS-NPs) were fabricated and optimized using polylactide-co-glycolic acid (PLGA), chitosan (CS), and polyvinyl alcohol (PVA) as the independent factors. Particle size, entrapment efficiency, release percent, and cumulative amount permeated after 24 h of DXH-PLGA-CS-NPs (dependent variables) were evaluated. The in-vivo biodistribution and pharmacodynamic studies were done in male Wistar rats. The optimized DXH-PLGA-CS-NPs had a vesicle size of 122.11 nm and EE% of 66.95 with 77.65% release and Q 24 of 555.34 (µg/cm2). Ex-vivo permeation study revealed 4-folds increase in DXH permeation from DXH-PLGA-CS-NPs after 24 h compared to DXH solution. Intranasal administration of optimized DXH-PLGA-CS-NPs resulted in significantly higher (p < 0.05) C max , AUC total , t 1/2 , and MRT in rat brain and plasma than oral DXH solution. Pharmacodynamics investigation revealed that intranasally exploited optimal DXH-PLGA-CS-NPs could be deemed a fruitful horizon for DXH as a treatment for depression. [Display omitted] [ABSTRACT FROM AUTHOR]

Nanomedicine has emerged as an important approach for targeting RA medication. Rheumatoid arthritis (RA) is a widespread autoimmune disorder marked by multiple inflamed joints. Gold nanoparticles (GNPs) have been demonstrated as efficacious nanocarriers due to their unique characteristics and the relative simplicity of their synthesis in varied sizes; moreover, they have the capability to alleviate several inflammatory markers. The current objective was to combine methotrexate (MTX) with GNPs to overcome MTX restrictions. GNPs were fabricated by a chemical reduction technique, utilizing sodium citrate and tween 20. The MTX-GNPs formulations were characterized in vitro by % entrapment efficiency (%EE), particle size, polydispersity index (PDI) zeta potential, and % release. The MTX-GNPs formulation was administrated as an intra-articular solution, and additionally, incorporated into a Carbopol gel to investigate its anti-arthritic effectiveness and bioavailability in vivo. The results indicated that a %EE of 87.53 ± 1.10%, and a particle size of 60.62 ± 2.41 nm with a PDI of 0.31 ± 0.03, and a zeta potential of −27.80 ± 0.36 mV were optimal. The in vitro release of MTX from the MTX-GNPs formulation demonstrated that the MTX-GNPs formulation's release was 34.91 ± 1.96% and considerably (p < 0.05) lower than that of free MTX, showing a significant difference in dissolution patterns (p < 0.05). In vivo, MTX-GNPs formulations inhibited IL-6 by 36.52%, ACCP (63.25 %), COMP (28.16%), and RANKL (63.67%), as well as elevated IL-10 by 190.18%. Transdermal MTX-GNPs decreased IL-6 by 22.52%, ACCP (56.63%), COMP (52.64%), and RANKL (79.5%), as well as increased IL-10 by 168.37%. Histological investigation supported these recent findings. Conclusions: Marked improvements in MTX anti-arthritic effects are seen when it is conjugated to GNPs. [ABSTRACT FROM AUTHOR]

Losartan potassium-laden pegylated nanocubic vesicles (LP-NCVs-PEG) have an intriguing kidney-targeted nanoplatform for acute renal injury via blocking apoptosis and activating wnt/β-catenin pathway. Utilizing a thin-film hydration methodology established on 42 full factorial design to produce LP loaded nanocubic formulations (LP-NCVs) which composed mainly from L-α-phosphatidylcholine and poloxamer. The optimization process was designed to select the formulation with maximum entrapment efficiency (EE %), maximum in-vitro drug release (Q 8h), and minimum vesicle size (VS). The optimum formulation was then pegylated to obtain LP-NCVs-PEG formulation that shields NCVs from the harsh ecosystem of the stomach, improves their oral drug delivery performance and targets the proximal renal tubules with no systemic toxicity. Male albino rats were injected with Cisplatin (6 mg/kg, i.p.) alone or with LP-formulations (5 mg/kg/day). Kidney injury markers, inflammatory markers, apoptotic markers. Besides renal tissue expression of Wnt, β-Catenin, GSK-3β, renal RNA gene expression of TCF-4, LEF-1 and histopathology were also analyzed to display pharmacological study. The pharmacokinetics studies demonstrated that LP-NCVs-PEG boosted LP bioavailability approximately 3.61 times compared to LP oral solution. Besides LP-NCVs-PEG may have an intriguing kidney-targeted nanoplatform for acute renal injury via decreased renal toxicity markers, renal expression of LEF-1, GSK3-β, caspase, TNF-α, NF-κB and TUNEL expression. Alternatively, increased renal tissue level of Bcl-2, wnt, β-catenin and TCF-4. LP-NCVs-PEG improved LP pharmacokinetics targeting the kidney and improved injury by activating wnt/β-catenin/TCF-4 pathway, blocking apoptosis, inflammation and renal toxicity markers suggesting it might be successful nephroprotective adjuvant therapy. [Display omitted] [ABSTRACT FROM AUTHOR]

A novel CuWO4/SiO2 heterojunction catalyst was successfully synthesized using a new sulfonamide derivative. The physical characteristics of the prepared samples were investigated by TGA, XRD, FTIR, SEM, UV, PL, and XPS. The prepared catalysts were applied as a nano photocatalyst for photooxidative desulfurization of dibenzothiophene under visible light using hydrogen peroxide as an oxidant. The photocatalytic oxidative desulfurization performances of the prepared samples were investigated. Various factors as the reaction time, dibenzothiophene concentration, catalyst dose, and the oxidizing agent dose were also studied. The prepared photocatalyst has high desulfurization activity in the removal of DBT under mild conditions. Results showed that the CuWO4/SiO2 exhibited considerably higher activity than neat support SiO2. Such improved photocatalytic activity is mainly attributed to the efficient separation of photogenerated electron–hole pairs on CuWO4/SiO2 heterojunction. Moreover, the synergistic effects of this photocatalytic oxidation and the green oxidant hydrogen peroxide played an essential role in desulfurization. The reaction is pseudo-first-order and can reach 98.6% removal of dibenzothiophene after 70 min and 97.2% after four cycles. [ABSTRACT FROM AUTHOR]

Background: Metformin has been reported to have an anti-tumorigenic impact against metastatic breast cancer (MBC) cells through several mechanisms. Its effect can be evaluated by using many variables such as the response rate (RR) as well as the progression-free survival (PFS). Materials and methods: A prospective study was conducted to investigate and estimate the metformin effect on MBC. About 107 subjects were included in the study and were divided into two groups: Group A included non-diabetic MBC patients treated with metformin in conjunction with chemotherapy and group B included those treated with chemotherapy alone. Both PFS and RR were used as a criteria to evaluate the treatment outcome. Associated adverse effects of metformin were also assessed. Results: The average age of the participants in group A and group B was 50 vs. 47.5, respectively. No significant differences were detected between both cohorts concerning RR levels (regression disease (RD) 27.8% vs. 12.5%, stationary disease (SD) 44.4% vs. 41.7%, progression disease (PD) 27.8% vs. 45.8%, respectively, p = 0.074). Moreover, PFS showed no significant difference between both groups (p = 0.753). There was no significant correlation between metformin concentration and their adverse effects on the study participants. Conclusion: Metformin as an adjuvant therapy to MBC undergoing chemotherapy showed no significant survival benefit as determined by RR and PFS. [ABSTRACT FROM AUTHOR]

A new series of chromone and furochromone-based sulfonamide Schiff's base derivatives 3–12 were synthesized and evaluated for their antimicrobial activity against S. aureus , E. coli , C. albicans , and A. niger using agar diffusion method. Compound 3a demonstrated potent antimicrobial activities with MIC values of 9.76 and 19.53 μg/mL against S. aureus , E. coli and C. albicans , which is 2-fold and 4-fold more potent than neomycin (MIC = 19.53, 39.06 μg/mL respectively). To improve the effectiveness of 3a , it was encapsulated into chitosan nanoparticles (CS-3aNPs). The CS-3aNPs size was 32.01 nm, as observed by transmission electron microscope (TEM) images and the zeta potential value was 14.1 ± 3.07 mV. Encapsulation efficiency (EE) and loading capacity (LC) were 91.5 % and 1.6 %, respectively as indicated by spectral analysis. The CS-3aNPs extremely inhibited bacterial growth utilizing the colony-forming units (CFU). The ability of CS-3aNPs to protect skin wounds was evaluated in vivo. CS-3aNPs showed complete wound re-epithelialization, hyperplasia of the epidermis, well-organized granulation tissue formation, and reduced signs of wound infection, as seen through histological assessment which showed minimal inflammatory cells in comparison with untreated wound. Overall, these findings suggest that CS-3aNPs has a positive impact on protecting skin wounds from infection due to their antimicrobial activity. [Display omitted] [ABSTRACT FROM AUTHOR]

• Compounds formula, (E)−5-heptadecyl-4-(((1-benzyl-1 H -indol-3-yl) methylene) amino)−4 H -1,2,4-triazole-3-S-alkyl, where the alkyl group is ethan-1-ol (6d) or propane-1,2-diol)7d(showed antiviral activity against NRC-03-nhCoV with IC 50 of 8.7 and 8.925 μM, respectively. • (E)−5-heptadecyl-4-(((1-methyl-1 H -indol-3-yl)methylene)amino)−4 H -1,2,4-triazole −3-thiol (5b) showed excellent MIC values against all test microbes with values of 19.53, 39.06, and 39.125 µg/mL against S. aureus, E. coli , and C. albicans, respectively. • Compound 5b exhibited release of reducing sugars and proteins with variable values on test microbes, which confirmed the effect of 5b on the bacterial cell well (biosynthesis of cell well peptidoglycan). • Compound 5b was confirmed to be able to disrupt outer and inner membranes and interact with membrane protein and intracellular targets by scanning electron microscopic study (SEM). • A molecular docking study of the potent compounds against the key viral and microbial protein targets has highlighted the antiviral and antimicrobial behavior of these compounds. Two series of Schiff bases and Mannich bases derived from 5-heptadecyl-4 H -1,2,4-triazole hybrids of indole moiety have been synthesized. First, the acid-catalyzed reaction of N -substituted-1 H -indole-3-carboxaldehydes with the modified fatty acid, 4-amino-5-heptadecyl-4 H -1,2,4-triazole-3-thiol, afforded 1,2,4-triazole Schiff bases 5a-d. Treatment of 5a-d with some halo-compounds gave S -alkyl-1,2,4-triazoles 6a-d to 9a-d. Additionally, the reaction of 5a-d with different secondary amine and paraformaldehyde afforded Mannich base products 10a-d to 13a-d. Basically, viral infections are often followed by bacterial infections that require antimicrobial treatment. The antiviral bioassay revealed that compounds 6d and 7d exhibited significant antiviral activity against NRC-03-nhCoV with IC 50 equal 8.7 and 8.925 μM, respectively. Next, the synthesized compounds were evaluated for their antimicrobial activity against Gram-positive and Gram-negative bacteria as well as yeast and fungi. Compound 5b exhibited effective antimicrobial activities against all microbial test strains. 5b revealed MIC values of 19.53 μg/mL against S. aureus, 39.063 μg/mL against E. coli , and 39.125 μg/mL against C. albicans. On top of that, the release of reducing sugars and proteins from the treated bacterial strains over the untreated bacterial strains was undertaken to describe the effect of compound 5b on the intact cells. Furthermore, scanning electron microscopy (SEM) has been applied to study the possible sterilization process of the antimicrobial compound 5b. The results indicated the possibility of destroying the cell membrane structure of microbes, resulting in incomplete microbial structures, and thus achieving inhibition. To putatively highlight the antiviral and antimicrobial activities of the potent compounds, they were subjected to molecular docking against the key viral and microbial protein targets. [ABSTRACT FROM AUTHOR]

Chronic wounds are a serious problem that could cause severe morbidity and even death. The ability of statins including rosuvastatin calcium (RVS) to enhance wound healing was well reported. However, RVS is poorly soluble and has low bioavailability. Thus, this study aimed to prepare and evaluate RVS-loaded nanocubics to enhance its skin performance. In addition, silver nanoparticles (AgNPs) exhibited potent antimicrobial activity, thus, the optimum RVS-loaded nanocubics was capped with AgNPs to evaluate its effect in wound management. Box–Behnken design was adopted to prepare RVS nanocubics. The design investigated the effect of lecithin, poloxamer 407 concentrations and hydration time on vesicle size, zeta potential (ZP), entrapment efficiency (EE%) and in vitro drug release%. Optimum formulation capped with AgNPs was incorporated into a gel base and examined for wound healing efficiency using different pharmacological tests in rats. Nanocubics have shown a mean diameter between 167.2 ± 7.8 and 408 ± 18.4 nm, ZP values ranging from −20.9 ± 1.9 to −53.5 ± 4 mV, EE% equivocated between 31.6 ± 1.4 and 94.4 ± 8.6 and drug release after 12 h between 17.9 ± 1.9 and 68.0 ± 4.0%. The histopathological studies and serum tumour necrosis factor alpha (TNF-α) and interleukin-1β (IL-1β) levels confirmed the greater efficacy of RVS nanocubics capped with AgNPs gel in wound healing when compared with gentamicin ointment. RVS-loaded nanocubic vesicles and AgNPs-loaded hydrogel could be considered as a promising platform to enhance the wound healing and tissue repair processes. [ABSTRACT FROM AUTHOR]

The present work is concerned with tailoring and appraisal of a novel nano-cargo; bilosomes (BLS) dual laded with doxylamine succinate (DAS) and pyridoxine hydrochloride (PDH), the first treatment option against gestational nausea and vomiting, for intranasal delivery. This bifunctional horizon could surmount constraints of orally-commercialized platforms both in dosage regimen and pharmacokinetic profile. For accomplishing this purpose, DAS/PDH-BLS were elaborated integrating phospholipid, sodium cholate and cholesterol applying thin-film hydration method based on Box-Behnken design. Utilizing Design-Expert® software, the effect of formulation variables on BLS physicochemical features alongside the optimal formulation selection were investigated. Then, the optimum DAS/PDH-BLS formulation was incorporated into a thermally-triggered in situ gelling base. The in vivo pharmacokinetic studies were explored in rats for intranasal DAS/PDH-BLS in situ gel compared with analogous intranasal free in situ gel and oral solution. The optimized BLS disclosed vesicle size of 243.23 nm, ζ potential of -31.33 mV, entrapment efficiency of 59.18 and 41.63%, accumulative % release within 8 h of 63.30 and 85.52% and accumulative permeated amount over 24 h of 347.92 and 195.4 µg/cm2 for DAS/PDH, respectively. Following intranasal administration of the inspected BLS in situ gel, pharmacokinetic studies revealed a 1.64- and 2.3-fold increment in the relative bioavailability of DAS and a 1.7- and 3.73-fold increase for PDH compared to the intranasal free in situ gel and oral solution, respectively besides significantly extended mean residence times for both drugs. Thus, the intranasally exploited DAS/PDH-BLS could be deemed as a promising hybrid nanoplatform with fruitful pharmacokinetics and tolerability traits. [ABSTRACT FROM AUTHOR]

This study aimed to detect the incidence, seasonal variation, age susceptibility of domestic pigeon to P. canariensis as well as ultra-morphological and molecular identification of circulating species (spp.) in Egypt. To achieve this aim; different pigeon premises in El- Gharbia governorate were investigated to correlate the findings with environmental factors responsible for parasitism. A total of two hundred pigeons (100 squabs and 100 adult) were examined for the presence of P. canariensis. during the period from March 2020 to March 2021. The incidence of P. canariensis was 64% among the examined birds. Higher incidence was recorded in young squabs than adults. P. canariensis infestation was predominant in both summer and spring seasons. The pigeon fly is a medium to large sized, flat with a flattened head, thorax and abdomen with short sheathed palpi (twice longer than broad). The wings are characterized by weak posterior veins, which have five veins behind the costal vein. The molecular characterization of this fly using the COX I (GenBank accession No. MW853922) was revealed that 704 bp, which displayed as 99.78% identity with the COI gene of Pseudolynchia sp. In a conclusion, to manage the external parasitism; sanitation and cleanliness are essential. Deltamethrin (Butox, 12.5 %) is effective insecticides periodically used as spray to overcome ectoparasites infestations for both bird and surrounding environment. [ABSTRACT FROM AUTHOR]

Broiler chicken's production considered a very important sector of Egyptian poultry production. Diarrhea is a common problem that Threaten poultry production. There are many causes of broiler chicken's diarrhea as; nutritional causes, infectious causes (viral, bacterial and parasitic). Larvae rarely infest and cause diarrhea in chickens but if present they irritate intestinal mucosa which causes a secondary bacterial diarrhea. In our investigation, intestinal myiasis was reported as uncommon cause of broiler chicken diarrhea in Egypt. The collected larvae were identified using scanning electron microscope study which revealed that; it is 3rd larval stage of M. domestica; creamy white in color; the length of the larvae ranged from 10-12 mm (10.5 ± 0.3); the anterior end contain the black colored cephalopharyngeal skeleton; the anterior spiracles present in the 2nd segment and had a number ranged from 6 to 8 rounded spiracular openings. The spines present in the group resembles the combs which present in the spinose area. The spinose comb contains from 5 to 9 spines which is small and triangular with slightly tapering ends. The posterior peritremes contain three snake or S- shaped or even tortoise openings; with central button; the peritreme was complete; the distance between the two peritreme ranged from 70- 100 μm in length. [ABSTRACT FROM AUTHOR]

In this paper Chen-Burr XII distribution is constructed and graphical description of the probability density function, hazard rate and reversed hazard rate functions of the proposed model is obtained. Also, some statistical characteristics of the Chen-Burr XII distribution are discussed and some new models as sub-models from the Chen-Burr XII distribution are introduced. Moreover, maximum likelihood estimation of the parameters, reliability, hazard rate and reversed hazard rate functions of the Chen-Burr XII distribution are considered. Also, the asymptotic confidence intervals of the distribution parameters, reliability, hazard rate and reversed hazard rate functions are presented. Finally, three real life data sets are applied to prove how the Chen-Burr XII distribution can be applied in real life and to confirm its superiority over some existing distributions. [ABSTRACT FROM AUTHOR]

Triaryl-(Z)-olefin (TZO) was synthesized as a Tamoxifen (TMX) analogue for breast cancer treatment to avoid developing the resistance and toxicity of TMX. TZO was synthesized using McMurry olefination reaction and has anti-cancer activity better than TMX by two folds. In this paper, in situ pH-sensitive TZO-loaded noisome hydrogel was prepared for delivering and targeting TZO to its site of activity. Equi-molar of cholesterol and span 60 was used to prepare TZO-loaded niosomes using the Hand Shaking Method. The central composite experimental design was used to prepare differently in situ pH-sensitive TZO-loaded niosomes formulae. The formulae were done by incorporated TZO-loaded niosomes into different concentrations of chitosan and Glyceryl monooleate (GCM). Increasing the chitosan and GCM concentrations resulted in significantly increasing the viscosity and significantly decreasing the release of TZO from different formulae. The formula composed of (0.61% w/v) of chitosan and (0.23% w/v) of GCM was chosen as an optimum formula to evaluate the efficacy of TZO using Ehrlich carcinoma mice model. A significant anti-tumour effect was shown in comparison with TMX. Briefly, in situ pH-sensitive TZO-loaded niosomes could be an effective treatment for breast cancer. [ABSTRACT FROM AUTHOR]

Background: Encephalitozoon cuniculi is an important microsporidian parasite with zoonotic potential. The present study highlights the impact of encephalitozoonosis on rabbit health in Egypt. Three rabbit farms in Giza, with a total of 16,400 rabbits were investigated due to occurrence of rabbits displaying clinical signs consistent with encephalitozoonosis. Results: Clinical signs observed during a 4 months observation period in 2018 included vestibular disease, paresis, limb paralysis, cataracts, phacoclastic uveitis, frequent urination, marked decrease in body weight and in some pregnant females, also repeated abortions. The total morbidity rates in adult and young rabbits were 76.7% and 81.5%, respectively. The highest mortality rate was recorded in offspring (12.3%), followed by dams (5.6%), and the lowest recorded mortality rate was in males (0.04%). Post-mortem findings included enteritis, pale enlarged kidneys, congested leptomeninges, focal brain necrosis, and endometrial congestion. Histopathological examination revealed nonsuppurative meningoencephalitis and glial nodules with central necrosis in the brain, vacuolation and necrosis of renal tubular epithelium, and corneal ulceration and ruptured lens capsule with fragmentation of lenticular fibres. E. cuniculi were observed in the brain, retinal ganglion cells, kidneys, and liver. Transmission electron microscopy examination revealed the presence of different developmental stages of E. cuniculi in the brain and kidney. Presence of E. cuniculi was confirmed by conventional polymerase chain reaction using a universal 16S gene for Encephalitozoon spp. followed by sequencing and sequence analysis. Conclusions: The presence of E. cuniculi in rabbits was confirmed at three farms in Egypt. Nervous signs and ocular lesions were the most predominant findings in these farms. [ABSTRACT FROM AUTHOR]

Maturity-onset diabetes of the young (MODY) is a group of monogenetic forms of diabetes mellitus caused by mutations in genes regulating ß-cell development and function. MODY represents a heterogeneous group of non-insulin-dependent diabetes arising in childhood or adult life. Interestingly, clinical heterogeneity in MODY patients like variable disease onset and severity is observed even among individual family members sharing the same mutation, an issue that is not well understood. As high blood glucose levels are a well-known factor promoting ß-cell stress and ultimately leading to cell death, we asked whether additional ß-cell stress might account for the occurrence of disease heterogeneity in mice carrying a MODY4 mutation. In order to challenge ß-cells, we established a MODY4 animal model based on Pdx1 (pancreatic and duodenal homeobox 1) haploinsufficiency, which allows conditional modulation of cell stress by genetic inhibition of the stress-responsive IKK/NF-κB signalling pathway. While Pdx1+/- mice were found glucose intolerant without progressing to diabetes, additional challenge of ß-cell function by IKK/NF-κB inhibition promoted rapid diabetes development showing hyperglycaemia, hypoinsulinemia and loss of ß-cell mass. Disease pathogenesis was characterized by deregulation of genes controlling ß-cell homeostasis and function. Importantly, restoration of normal IKK/NF-κB signalling reverted the diabetic phenotype including normalization of glycaemia and ß-cell mass. Our findings implicate that the avoidance of additional ß-cell stress can delay a detrimental disease progression in MODY4 diabetes. Remarkably, an already present diabetic phenotype can be reversed when ß-cell stress is normalized. [ABSTRACT FROM AUTHOR]

Resveratrol is a promising neuroprotective agent against neurodegenerative disorders such as Alzheimer's disease. Resveratrol-loaded transferosomes and nanoemulsions were developed and labelled with gold nanoparticles (GNPs). The water maze test was utilised to identify the effect on spatial memory recovery. The treated rats were examined for cellular uptake and bioaccumulation of drug in the brain using computed tomography (CT) and histopathological examination utilising GNPs as a biomarker. Compared with nanoemulsions, transferosomes displayed higher permeation of up to 81.29 ± 2.64% and higher fluorescence intensity with p <.05. Transferosomes significantly enhanced behavioural acquisition and spatial memory function in the amnesic rats compared with both the nanoemulsion formulation and the pure drug. CT effectively demonstrated the accumulation of GNPs in the brains of all treated rats, while superior accumulation of GNPs was observed in the rats that received the transferosome formulation. The histopathology also demonstrated GNP accumulation in the nuclei and cytoplasm in the brain tissues of both the transferosome- and nanoemulsion-treated groups. Therefore, the developed transferosomes may be considered as a well-designed brain targeting system that might further be applied for targeting many drugs to be used in the treatment of central nervous system diseases. [ABSTRACT FROM AUTHOR]

This paper introduces a new four-parameter additive model, named xgamma-Burr XII distribution, by considering two competing risks: the former has the xgamma distribution and the latter has the Burr XII distribution. A graphical description of the xgamma-Burr XII distribution is presented, including plots of the probability density function, hazard rate and reversed hazard rate functions. The xgamma-Burr XII density has different shapes such as decreasing, unimodal, approximately symmetric and decreasing-unimodal. The main statistical properties of the proposed model are studied. The unknown model parameters, reliability, hazard rate and reversed hazard rate functions are estimated via the maximum likelihood method. The asymptotic confidence intervals of the parameters, reliability function, hazard rate function and reversed hazard rate function are also obtained. A simulation study is carried out to evaluate the performance of the maximum likelihood estimates. In addition, three real data are applied to show the superiority of the xgamma-Burr XII distribution over some known distributions in real-life applications. [ABSTRACT FROM AUTHOR]

• Sulfonamide-tethered coumarin derivatives exhibited antimicrobial activity. • 2-Oxo- N -(6-oxo-2-thioxo-1,2,3,6-tetrahydropyrimidin-4-yl)−2 H -chromene-6-sulfonamide (12) showed excellent MIC values, IC 50 = 4.88, 39.06, and 9.76 µg/mL against S. aureus, E. coli and C. albicans, respectively. • Compound 12 strongly inhibited DNA gyrase (IC 50 =1.793μg/ml) closely equipotent with the reference drug, novobiocin (NOV, IC 50 = 1.425μg/ml). • In-Silico study including molecular docking and ADME confirmed the drug-likeness behavior of compound 12. A new series of coumarin-6-sulfonamide derivatives 3–16 have been synthesized via simple and convenient coupling reaction of coumarin-6-sulfonyl chloride with different sulfa drugs and various amino-heterocycles. The antimicrobial activity of the new compounds was evaluated against S. aureus ATCC 6538, E. coli ATCC 25933, C. albicans ATCC 10231, and A. niger NRRL A-326. Compound 12 showed potent antimicrobial activities against all pathogenic strains, with MIC values of 4.88 μg/mL against S. aureus and 9.76 μg/mL against C. albicans , exceptionally 4-fold more potent than neomycin control drug (MIC= 19.53 and 39.06 μg/mL respectively), and an MIC value of 39.06 μg/mL against E. coli , equipotent with neomycin. Meanwhile, compound 10 was equipotent with neomycin against both S. aureus and C. albicans. Additionally, compound 14 was equipotent with neomycin against S. aureus , and 2-fold more potent that neomycin against C. albicans. Further investigations showed that compounds 10 and 12 strongly inhibited DNA gyrase (IC 50 = 2.463 and 1.793μg/mL respectively), with compound 12 being closely equipotent with the reference novobiocin drug (IC 50 = 1.425μg/mL). Docking studies of compounds 10 and 12 on the active site of DNA gyrase confirmed their ability to form stable complexes with the target enzyme. According to ADME data, the bioavailability profile of compound 12 was high, and its physicochemical and pharmacological characteristics were consistent with Lipinski's RO5 anticipated constraints. Collectively, these data strongly highlight the efficiency of our multidisciplinary approach in the field of novel potent antimicrobial DNA gyrase inhibitors. [Display omitted] A new series of coumarin-6-sulfonamides 3–16 have been synthesized and evaluated for their antimicrobial activity and DNA-gyrase inhibition. The results revealed that compounds 10 and 12 strongly inhibited DNA gyrase (IC 50 = 2.463 and 1.793μg/mL respectively), with compound 12 being closely equipotent with the reference novobiocin drug (IC 50 = 1.425μg/mL). In-Silico studies including molecular docking study and the drug-likeness of compound 12 according to Lipinski's rule of five, and some prediction of physicochemical and pharmacokinetic (ADME) confirmed that compound 12 has a high bioavailability profile. [ABSTRACT FROM AUTHOR]

This document is a correction notice for an article titled "Synthesis of novel solid scale inhibitors based on silver tungstate loaded KIT-6 for scale removal from produced water: static and modeling evaluation." The authors apologize for an incorrect figure in the original manuscript and provide the correct figure and caption. The article was published in Dalton Transactions, an international journal of inorganic chemistry. The authors are affiliated with the Egyptian Petroleum Research Institute. [Extracted from the article]

The oral administration of celecoxib (CLX) is a real problem because of its low aqueous solubility that results in high variability in absorption and its severe adverse effect such as cardiotoxic effects and gastrointestinal toxicity. Self-nanoemulsifying drug delivery systems (SNEDDS) can enhance the poor dissolution and erratic absorption of poorly water-soluble drugs such as CLX. This study was conducted to investigate the potential of SNEDDS to enhance the efficacy of CLX on inflamed mucous tissue and reduce systemic adverse effects by increasing its poor dissolution properties. A pseudo-ternary phase diagram was derived from the results of CLX solubility experiments in various excipients. These studies revealed the use of Labrafil M 2515 CS as oil, tween 80 as a surfactant, and polyethylene glycol 400 as a co-surfactant for the optimization of SNEDDS formulations. Eight formulations were formulated and characterized by their particle size, polydispersity index, viscosity, globular shape, drug solubility, self-emulsification efficiency, in vitro drug release, and permeation. The anti-inflammatory effect of CLX-SNEDDS was evaluated by carrageenan-induced cheek oedema in rats. The cheeks were treated with CLX-SNEDDS before oedema induction and then noticed for narrow periods (2 h) followed by histopathological studies to determine the efficacy of treatment. The selected formulations (F3 and F5) showed spherical morphologies under transmission electron microscopy, mean droplet sizes of 116.9 ± 1.78 and 124 ± 1.87 nm, respectively, complete in vitro drug release, and high cumulative amounts of drug permeation in 8 h. They also showed significant remarkable cheek oedema inhibition in comparison with the control groups (p < 0.05). CLX-SNEDDS was found to achieve effective local therapeutic concentration and intended to reduce cheek oedema, congestive capillary, inflammatory cells, and side effects due to lower dose size. [ABSTRACT FROM AUTHOR]

Bio-identical progesterone (PRG) is an exogenous female steroidal hormone which is used for treatment of polycystic ovary syndrome (PCOS). However, it suffers from poor bioavailability due to hepatic metabolism and poor solubility. The target of this work was to evaluate and statistically optimize PRG-loaded nanovesicle transethosomes (NVTEs) based in mucoadhesive gel for transvaginal delivery of PRG as potential luteal-phase support. A 24 full factorial design was used to explore the effect of phosphatidylcholine (PC), Tween 80, cetyltrimethyl ammonium bromide and ethanol concentration on particle size, entrapment efficiency (EE%), % in vitro PRG release after 24 h and transvaginal flux. PRG-loaded NVTEs were prepared by injection sonication method. The results revealed that the mean particle sizes ranged from 133.3 ± 3.42 to 349.5 ± 1.24 nm, zeta potential ranged from –23.5 ± 3.84 to +74.6 ± 4.97 mV, EE% ranged from 87.93 ± 3.58 to 97.05 ± 2.61%, % PRG release ranged from 50.9 ± 2.75 to 90.69 ± 2.07 and transvaginal flux ranged from 0.274 ± 0.03 to 0.531 ± 0.04 mg/cm2/h. The optimized formulation was subjected to transmission electron microscope for morphological examination and then incorporated in the mucoadhesive vaginal gel using Carbopol 974, hydroxyl propyl methylcellulose and sodium alginate. The optimized formulation was clinically studied in anovulatory PCOS and showed a significant increase in the serum PRG, endometrial thickness, echogenicity degree and the pregnancy rate. Briefly, PRG-loaded NVTEs vaginal gel might be a promising formulation for luteal phase support and increase pregnancy rate in anovulatory PCOS. [ABSTRACT FROM AUTHOR]

Due to the most recent environmental requirements, wide desulfurization has become an increasingly important way to obtain ultra-clean fuels for transportation of less than 15 ppm of sulfur, such as diesel, gasoline, and jet fuel. As a result of the strict requirements for transportation fuels. Therefore, we report a novel sandwich-type [(FeW 9 O 34) 2 Fe 4 (H 2 O) 2 ]−10 Fe 6 W 18 O 70 cluster incorporated zirconium ferrite (ZrFe 2 O 5) catalyst composite to successfully remove sulfur. The structural properties of these samples were systematically investigated by X-ray powder diffraction (XRD), Brunauer-Emmett-Teller (BET), Fourier transform infrared spectroscopy (FT-IR), scanning electronic microscopy (SEM), X-ray photoelectron spectroscopy (XPS) and thermal techniques. A series of Ultrasound assisted oxidative desulfurization UAODS processes were carried out to evaluate the optimization of the desulfurization performance catalysts prepared in this work. As well as the reactivity of various sulfur compounds. Fe 6 W 18 O 70 @ZrFe 2 O 5 removed sulfur (98.2%) in 40 min and could be regenerated five times with no loss of sulfur removal. In addition, the catalyst's reaction mechanism for the UAODS process was investigated. [ABSTRACT FROM AUTHOR]

The avian digestive tract is an important system for converting ingested food into the nutrients their bodies need for maintenance, growth, and reproduction (meat, table eggs, and fertile eggs). Therefore, preserving digestive system integrity is crucial to bird health and productivity. As an alternative to antibiotics, the world has recently turned to the use of natural products to enhance avian development, intestinal health, and production. Therefore, the primary goal of this review is to explain the various characteristics of the avian digestive tract and how to enhance its performance with natural, safe feed additives such as exogenous enzymes, organic acids, photogenic products, amino acids, prebiotics, probiotics, synbiotics, and herbal extracts. In conclusion, the composition of the gut microbiome can be influenced by a number of circumstances, and this has important consequences for the health and productivity of birds. To better understand the connection between pathogens, the variety of therapies available, and the microbiome of the gut, additional research needs to be carried out. [ABSTRACT FROM AUTHOR]

Background: Rosuvastatin (ROS) calcium is the latest synthetic drug in the statin group that has an anti-hyperlipidemic activity. It is available as tablets, and its poor aqueous solubility, slow dissolution rate and low-absorption extent result in less than 20% bioavailability and about 80% being excreted unchanged in the feces without absorption. Objective: To utilize nanotechnology to reformulate ROS as a self-nano-emulsifying drug delivery system (SNEDDS), and utilizing design optimization to fabricate the SNEDDS as a tablet. Methods: The solubility of ROS in different oils, surfactants and co-surfactants was tested. Pseudo-ternary phase diagrams were developed and various SNEDDS formulations were prepared and evaluated regarding globule size, self-emulsification, viscosity and transmittance. The optimized system was examined using transmission electron microscopy. The self-nano-emulsifying tablets were prepared using two types of nano-silica and different percentages of Avicel as a binder and Ac-Di-Sol as a disintegrant. The prepared tablets were evaluated for their physicochemical properties. Bioavailability in human volunteers was assessed. Results: A SNEDDS system was successfully developed with a droplet size range of 15 nm and a composition of 10% Labrafac, 80% Cremophore RH40 and 10% Propylene glycol. The optimized tablet formula contained: hydrophilic nano-silica, 3% Ac-Di-Sol and 30% Avicel. The pharmacokinetic study revealed that the bioavailability was enhanced by more than 2.4-fold compared with the commercially available tablet. Conclusions: Tablets containing SNEDDS loaded with ROS represent a promising novel formula that has higher gastrointestinal absorption and enhanced systemic bioavailability. [ABSTRACT FROM AUTHOR]

Background: Alendronate Sodium (ALDS) is the drug of choice for treatment of osteoporosis. However, 50% of the osteoporotic patients ceased the treatment within the first year due to its potential side effect on the gastrointestinal tract (GIT). Objective: The current study aimed to utilize nanotechnology to develop a nano-oral liposomal preparation containing biodegradable polymer (Starch) that enhance the drug prosperities. Methods: Nanoliposomes of ALDS were prepared using different concentrations of solubilized starch (0.1 - 0.5 g ) by thin film hydration method. A new method of alendronate quantitative determination was used to overcome the obstacle of its determination by using a new highly sensitive derivatization method. The selected formula was visualized using TEM, in vitro release studies and Stability study was also carried out. Furthermore, ulcerogenicity studies were performed to compare between the optimum prepared formula and a standard nonliposomal ALDS. Results: Six nano-oral liposomal formulations were prepared with zeta potentials ranging from -12 mV to -39 mV and a particle size ranging from 94 nm to 298 nm. The encapsulation efficiency studies demonstrated that the amount of ALDS entrapped within liposomes increased with increasing starch concentration. The stability studies confirmed the role of starch in increasing the stability of the prepared liposomes. In vitro release studies have demonstrated a relative delay in ALDS releases from the liposome core. Ulcerogenicity studies proofed that the prepared formula has a significant gastric tolerance. Conclusion: a novel liposomal formula of ALDS was developed with better tolerability. However, further clinical investigations are necessary to evaluate its therapeutic effectiveness. [ABSTRACT FROM AUTHOR]

Many pathogens that cause chronic diseases in birds use the respiratory tract as a primary route of infection, and respiratory disorders are the main leading source of financial losses in the poultry business. Respiratory infections are a serious problem facing the poultry sector, causing severe economic losses. Avian influenza virus, Newcastle disease virus , infectious bronchitis virus , and avian pneumovirus are particularly serious viral respiratory pathogens. Mycoplasma gallisepticum , Staphylococcus, Bordetella avium, Pasteurella multocida , Riemerella anatipestifer , Chlamydophila psittaci , and Escherichia coli have been identified as the most serious bacterial respiratory pathogens in poultry. This review gives an updated summary, incorporating the latest data, about the evidence for the circulation of widespread, economically important poultry respiratory pathogens, with special reference to possible methods for the control and prevention of these pathogens. [Display omitted] [ABSTRACT FROM AUTHOR]

Climatic changes and elevated ambient temperature are significant environmental stressors with a negative impact on birds' physiological, immunological, and behavioral status, increasing their susceptibility to stressors and immunosuppression and consequently increasing intestinal permeability (leaky gut). Prebiotics have been utilized to stop or diminish the harmful effects of stress in chickens. We aimed to evaluate the role of mannan-oligosaccharides, and beta-d-glucan prebiotics supplements in drinking water against experimentally induced heat stress (HS) on broiler chickens and study their impact on birds' performance, gut microbiome, and immune response. A total of 120 1-day-old Ross broiler chicks were allocated into four groups (30 birds/group), and each group was subdivided into triplicates (10 birds each). The experimental groups were classified as follows; the 1st (G1) control birds, the 2nd (G2) birds exposed experimentally to HS, the 3rd (G3) birds administered prebiotics in drinking water without exposure to HS, and the 4th (G4) birds exposed to HS and administered prebiotics in drinking water. After each vaccination, blood samples and serum samples were collected to evaluate the birds' immune status. Fecal samples were also collected for the molecular evaluation of the gut microbiome based on the genetic analyses and sequencing of 16S rRNA gene. The results showed that HS has reduced the birds' performance and badly affected the birds' immune response and gut microbiome. However, the addition of prebiotics to drinking water, with or without stress, enhanced the growth rate, maintained a normal gut microbiome, and improved immune parameters. Moreover, the usage of prebiotics improved the chicken gut microbiome and alleviated the negative effect of heat stress. Administering prebiotics significantly (p < 0.05) increased the relative abundance of beneficial bacteria and eradicated pathogenic ones in the birds' gut microbiome. Prebiotics showed a positive effect on the gut microbiome and the immune status of chickens under HS in addition to their efficacy as a growth promoter. [ABSTRACT FROM AUTHOR]

Purpose: Voriconazole has both low aqueous solubility and stability. We hypothesize that designing voriconazole in the form of a nano powder inhaler at a geometric diameter within 1–5 μm will enhance its stability and solubility. Therefore, we prepared nanoagglomerates of voriconazole which will collapse in the lungs to reform the nanoparticles. Method: The nanoparticles were formulated using both stearic acid and sodium deoxycholate as edge activators. Osmogenic polycation polyethyleneimine (PEI) was used to form agglomerates of controllable size. Results: Voriconazole nanoparticles and agglomerates showed a significant higher cumulative drug release than the pure powder (p < 0.05) withR2 = 0.95. Small-sized particles were formed (353 nm), while their zeta potential was −30.7 mV. The agglomerates were 2.7 μm in size and their zeta potential was −20.9 mV. The formation of porous agglomerates was confirmed using a transmission electron microscope. Cascade impactor was used to evaluate the aerodynamic properties of the nanoparticles and the agglomerates. The aerodynamic characterization of the nanoparticles and the agglomerates resulted in a significant smaller mass median aerodynamic diameter (MMAD) (p < 0.05) and higher fine particle dose (FPD) (p < 0.01), fine particle fraction (FPF) (p < 0.01), and total emitted dose (TED) (p < 0.01) than the pure powder. Conclusion: The results suggest that using the combination of edge activators and diluted polycationic polymer solution provides porous voriconazole nanoagglomerates in a respirable range, which is proved successful in enhancing both the deposition and the dissolution of water insoluble-drugs in the lung. [ABSTRACT FROM AUTHOR]

Context: The effective treatment of skin carcinoma is warranted for targeting the chemotherapeutic agents into tumor cells and avoiding unwanted systemic absorption. Objective:This work was dedicated to the purpose of engineering highly penetrating shell-enriched nanoparticles that were loaded with a hydrophilic chemotherapeutic agent, 5-fluorouracil (5-FU). Methods: Varying ratios of lecithin and poloxamer188 were used to produce shell-enriched nanoparticles by enabling the formation of reversed micelles within this region of the SLN. The localization of 5-FU within the shell region of the SLN, was confirmed using 5-FU nanogold particles as a tracer. SLN were introduced within sodium carboxy methylcellulose hydrogel, and then applied onto the skin of mice-bearing Ehrlich’s ascites carcinoma. The mice were treated with the gel twice daily for 6 weeks. Results: The transmission electron microscope (TEM) revealed the formation of uniform nanoparticles, which captured reversed micelles within their shell region. The SLNs’ had particle size that ranged from 137 ± 5.5 nm to 800 ± 53.6, zeta potential of −19.70 ± 0.40 mV and entrapment efficiency of 47.92 ± 2.34%. The diffusion of the drug-loaded SLN (269.37 ± 10.92 μg/cm2) was doubled when compared with the free drug (122 ± 3.09 μg/cm2) when both diffused through a hydrophobic membrane. SLN-treated mice exhibited reduced inflammatory reactions, with reduced degrees of keratosis, in addition to reduced symptoms of angiogenesis compared to 5-FU-treated mice. Conclusion: SLN possesses the capacity to be manipulated to entrap and release hydrophilic antitumor drugs with ease. [ABSTRACT FROM AUTHOR]

Climatic changes and elevated ambient temperature are significant environmental stressors with a negative impact on birds' physiological, immunological, and behavioral status, increasing their susceptibility to stressors and immunosuppression and consequently increasing intestinal permeability (leaky gut). Prebiotics have been utilized to stop or diminish the harmful effects of stress in chickens. We aimed to evaluate the role of mannan-oligosaccharides, and beta-d-glucan prebiotics supplements in drinking water against experimentally induced heat stress (HS) on broiler chickens and study their impact on birds' performance, gut microbiome, and immune response. A total of 120 1-day-old Ross broiler chicks were allocated into four groups (30 birds/group), and each group was subdivided into triplicates (10 birds each). The experimental groups were classified as follows; the 1st (G1) control birds, the 2nd (G2) birds exposed experimentally to HS, the 3rd (G3) birds administered prebiotics in drinking water without exposure to HS, and the 4th (G4) birds exposed to HS and administered prebiotics in drinking water. After each vaccination, blood samples and serum samples were collected to evaluate the birds' immune status. Fecal samples were also collected for the molecular evaluation of the gut microbiome based on the genetic analyses and sequencing of 16S rRNA gene. The results showed that HS has reduced the birds' performance and badly affected the birds' immune response and gut microbiome. However, the addition of prebiotics to drinking water, with or without stress, enhanced the growth rate, maintained a normal gut microbiome, and improved immune parameters. Moreover, the usage of prebiotics improved the chicken gut microbiome and alleviated the negative effect of heat stress. Administering prebiotics significantly (p < 0.05) increased the relative abundance of beneficial bacteria and eradicated pathogenic ones in the birds' gut microbiome. Prebiotics showed a positive effect on the gut microbiome and the immune status of chickens under HS in addition to their efficacy as a growth promoter. [ABSTRACT FROM AUTHOR]

Global climate change is accelerating at an unprecedented rate, and the consequences of global warming are expected to worsen. Many heat waves have recently hit various parts of the world, causing major losses in livestock, particularly in the poultry sector, resulting in massive mortalities and catastrophic economic losses. Therefore, the current review sheds light on the effects of heat stress on the poultry industry, and discusses the factors relevant to these harmful effects on behavior, bone development, blood chemistry and physiological changes, pathogenesis, and immune responses. Potential methods to ameliorate the heat stress response in birds, with particular reference to the role of probiotics in controlling such problems, is further discussed. • Heat stress (HS) causes huge losses in livestock production worldwide. • It increases HSP70 levels in brain, blood and liver. • Probiotics improve gut health, bird's histology and physiology HS. [ABSTRACT FROM AUTHOR]

This paper presents an 8-bit successive approximation analog to digital converter (SA-ADC) employing a mostly digital implementation for portable Electrocardiogram (ECG) detection systems. At 10 K samples/s, the proposed SA-ADC consumes $$1.87\,\upmu \hbox {W}$$ from a 1 V power supply. The layout and extraction of the proposed SA-ADC are done using L-edit and simulated using TSMC $$0.25\,\upmu \hbox {m}$$ technology file on Pspice. According to the simulation results, the SA-ADC has a signal-to-noise ratio of 57 dB, peak spurious-free dynamic range of 41 dB, and a signal-to-noise-and-distortion ratio of 40.5 dB for a 200 Hz- $$500\hbox {mV}_{\mathrm{pp}}$$ input sine wave. In addition to that, the SA-ADC has effective number of bits of 6.5-bits, an effective resolution bandwidth of 1.5 kHz and a figure of merit of 6.85 pJ/Conversion step. The digitized ECG signal is precisely reconstructed using a novel reconstruction circuit. These results show that the proposed SA-ADC in $$0.25\,\upmu \hbox {m}$$ technology is a good candidate for ECG detection systems. [ABSTRACT FROM AUTHOR]

[Display omitted] • Facile synthesis and characterization of {Mo 132 }/BiOCl composite. • {Mo 132 }/BiOCl composite show excellent catalytic performance in oxidative desulfurization of DBT(100%). • The stability of {Mo 132 }/BiOCl composite was investegated by cycling of ODS experiment. The Keplerate nanoball iso -polyoxomolybdate {Mo 132 } supported on BiOCl was prepared and assessed as a green, innovative, and low-cost oxidative desulfurization catalyst for dibenzothiophene-containing model oil (DBT). The XRD, FT-IR, Raman, SEM, TEM, BET, and XPS characterize the prepared catalysts. The optimum operating parameters were identified by evaluating factors such as reaction time, catalyst quantity, oxygen to sulfur molar ratio, and temperature. Experiments indicated that the catalyst was greatly efficient in removing DBT, with a sulfur removal rate up to 100 % at optimum conditions (catalyst dosage = 5 g/L, O/S = 10, time = 180 min, and temperature = 40 °C) utilizing hydrogen peroxide (H 2 O 2) as oxidizing agent and acetonitrile as extracting solvent. Furthermore, {Mo 132 }/BiOCl showed high stability and catalytic activity like that of the fresh one after four cycles. ODS activity of the catalyst was evaluated for various thiophenes (thiophene, BT, 4,6-DMDBT, and DBT) derivative and feed at optimum conditions. The proposed mechanism for catalytic oxidation of DBT in the existence of {Mo 132 }/BiOCl nanocomposite was studied. [ABSTRACT FROM AUTHOR]

In this investigation, the incidence and intensity of gastrointestinal parasites of domestic pigeons were evaluated, additionally, in vitro and in vivo evaluation of the antiparasitic activity of chitosan nanoparticles against the most predominant gut parasite. Therefore, 240 domestic pigeons (160 adults and 80 squabs) obtained from different localities in Giza governorate, Egypt, from February to July 2021, were subjected to parasitological and postmortem examination. The results revealed that 97% of pigeons were vulnerable to single or mixed gastrointestinal parasites. The detected helminths were identified as Capillaria columbae (C. columbae) with a total incidence of (12.5%), Ascaridia columbae (A. columbae) (83.3.%), Heterakis gallinarum (H. gallinarum) (18.7%), Raillietina cesticillus (R. cesticillus) (7.5%), Raillietina echinobothrida (R. echinobothrida) (29%), Choanotaenia infundibulum (C. infundibulum) (22.9%), Davainea proglottina (D. proglottina) (26.6%), and Cotugnia proglottina (C. proglottina) (14.5%). At the same time, the identified protozoan parasites were Trichomonas gallinae (T. gallinae), and Eimeria columbae (E. columbae), with a total incidence of 25 and 79%, respectively. Helminths and Eimeria infections were higher in adults than squabs, while T. gallinae infection was reported with a higher incidence in squabs (62.5%) than adults (6.2%). From our findings, A. columbae was the most predominant gut parasite in the examined pigeons. Thus, it was subjected to in vitro and in vivo treatment with chitosan nanoparticles. Serum and tissue samples were collected from the birds which have been used in the in vitro study to evaluate the oxidative stress markers as malondialdehyde (MDA), Nitric oxide levels and Tumor Necrosis Factor-alpha (TNF-α) and Interleukin-1β activity also, chitosan nanoparticles- treated worm ultrastructure were determined using scanning electron microscopy (SEM). Finally, we recommend periodic monitoring of pigeon's farm to detect the parasitic infestation, and from our results, we recommend chitosan nanoparticles as a potent nematocidal agent. [ABSTRACT FROM AUTHOR]

Coccidiosis is a devastating worldwide disease and is considered a dreadful disease in lovebirds. Indeed, a problem has been appeared cocktail lovebirds kept in a private pet birdhouse in Sheikh Zayed City, Giza, Egypt, in the shape of blood-tinged diarrhea, birds huddled together and showing signs of inappetence, ruffled feathers, unable to fly, general weakness and emaciation associated with high mortalities. Therefore, this study aimed to diagnose and find a suitable treatment to overcome such problems. To achieve this aim, blood and droppings samples were collected from infected and healthy birds for parasitological and hematological examinations, and tissue samples were collected from freshly dead birds for postmortem and histopathological examinations. A treatment trial was adopted on 50 infected birds and 25 healthy and parasitological negative birds and groups were classified as follows: group 1) 25 infected birds treated with Diclazuril, group 2) infected birds treated with Coccicure, and group 3) 25 birds kept as control negative reference birds. The parasitological identification revealed the presence of Eimeria aratinga ( E. aratinga ) oocysts in the infected bird intestine. Finally, we concluded that E. aratinga is a serious protozoon parasite infesting lovebirds revealing severe clinical signs, high mortalities, histopathological changes in the intestine and alteration in blood parameters. Diclazuril is an effective drug in treating E. aratinga in cocktail lovebirds. [ABSTRACT FROM AUTHOR]

Type 1 diabetes is a multifactorial inflammatory disease in genetically susceptible individuals characterized by progressive autoimmune destruction of pancreatic β-cells initiated by yet unknown factors. Although animal models of type 1 diabetes have substantially increased our understanding of disease pathogenesis, heterogeneity seen in human patients cannot be reflected by a single model and calls for additional models covering different aspects of human pathophysiology. Inhibitor of κB kinase (IKK)/nuclear factor-κB (NF -κB) signaling is a master regulator of inflammation; however, its role in diabetes pathogenesis is controversially discussed by studies using different inhibition approaches. To investigate the potential diabetogenic effects of NF-κB in β-cells, we generated a gain-of-function model allowing conditional IKK2/NF-κB activation in β-cells. A transgenic mouse model that expresses a constitutively active mutant of human IKK2 dependent on Pdx-1 promoter activity (IKK2-CAPdx-1) spontaneously develops full-blown immunemediated diabetes with insulitis, hyperglycemia, and hypoinsulinemia. Disease development involves a gene expression program mimicking virus-induced diabetes and allergic inflammatory responses as well as increased major histocompatibility complex class I/II expression by β-cells that could collectively promote diabetes development. Potential novel diabetes candidate genes were also identified. Interestingly, animals successfully recovered from diabetes upon transgene inactivation. Our data give the first direct evidence that b-cell--specific IKK2/NF-κB activation is a potential trigger of immune-mediated diabetes. Moreover, IKK2 CAPdx-1 mice provide a novel tool for studying critical checkpoints in diabetes pathogenesis and mechanisms governing b-cell degeneration/regeneration. [ABSTRACT FROM AUTHOR]

Salmonellosis is a severe problem that threatens the poultry sector worldwide right now. Salmonella gallinarium and Salmonella pullorum (Fowl typhoid) are the most pathogenic serovars in avian species leading to systemic infection resulting in severe economic losses in the poultry industry. Nontyphoidal serotypes of Salmonella (Paratyphoid disease) constitute a public health hazard for their involvement in food poisoning problems in addition to their zoonotic importance. Also, Salmonella species distribution is particularly extensive. They resisted environmental conditions that made it difficult to control their spread for a long time. Therefore, the current review aimed to through light on Salmonellosis in poultry with particular references to its pathogenesis, economic importance, immune response to Salmonella, Salmonella antibiotics resistance, possible methods for prevention and control of such problems using promising antibiotics alternatives including probiotics, prebiotics, symbiotics, organic acids, essential oils, cinnamaldehyde, chitosan, nanoparticles, and vaccines. [ABSTRACT FROM AUTHOR]

Acute liver failure (ALF) is considered a fatal clinical disorder and novel therapeutic interventions are mandatory. Naringenin is a flavonoid with anti-inflammatory, antioxidant and antiapoptotic effects that have displayed beneficial effects in different animal models of ALF. The current study aimed at investigating the hepatoprotective effect and the possible underlying molecular mechanisms of naringenin in lipopolysaccharide (LPS)/D-galactosamine (D-Gal) mouse model of ALF. Interestingly, naringenin pretreatment substantially alleviated LPS/D-Gal-induced liver injury, enhanced survival, improved liver function and ameliorated histopathological liver changes. Importantly, naringenin potently activated autophagy as evidenced by the increased Beclin-1 expression and LC3 II/LC3 I ratio. Furthermore, results demonstrated that naringenin alleviated oxidative stress by inducing nuclear factor-erythroid 2-related factor 2 (Nrf2) and increasing hepatic SOD activity and GSH level as well as ameliorated endoplasmic reticulum (ER) stress. Likewise, naringenin mitigated LPS/D-Gal-triggered inflammation by suppressing NF-κB and NLRP3 pathways. Accordingly, apoptotic cell death provoked by LPS/D-Gal challenge was markedly attenuated as depicted by the decrease in caspase-3 and p53 in naringenin-treated mice. To investigate the contribution of autophagy to naringenin-conferred hepatoprotection, autophagy was inhibited using 3-methyladenine (3 MA). Strikingly, 3 MA co-treatment abolished the hepatoprotective effect of naringenin, a finding that strongly suggests that naringenin-afforded protection is, at least in part, attributed to autophagy. Taken together, the present study revealed that naringenin exerted a prominent hepatoprotective effect by promoting autophagy with consequent attenuation of inflammatory responses, oxidative stress, ER stress and apoptosis. Our results provide evidence that naringenin use holds a promise as a potential therapeutic agent for ALF management. [Display omitted] • Naringenin protected against LPS/D-Gal-induced acute liver failure (ALF) in mice. • Naringenin enhanced survival and improved histopathological alterations in ALF. • Naringenin suppressed NF-κB/NLRP3/IL-1β inflammatory pathway. • Naringenin alleviated oxidative and ER stress and repressed hepatic apoptosis. • Naringenin afforded hepatoprotection in LPS/D-Gal mice via promoting autophagy. [ABSTRACT FROM AUTHOR]

Skin cancer is the most frequent cancer throughout the world. Vismodegib (VSD) is a hedgehog blocker approved for the prevention and treatment of skin cancer. VSD, however, is poorly bioavailable and has been linked to side effects. This work focused on designing a nano-invasome gel as a vehicle for enhancing the permeation, bioavailability, and efficacy of VSD. Additionally, the combined effect of terpenes and ethanol was studied on the permeation of VSD compared with liposomes. The prepared VSD-loaded invasomes (VLI) formulation included cineole (1%v/v), cholesterol (0.15%w/w), phospholipid (2%w/w), and ethanol (3%v/v) and displayed an entrapment efficiency of 87.73 ± 3.82%, a vesicle size of 188.27 ± 3.25 nm, and a steady-state flux of 9.83 ± 0.11 µg/cm2/h. The VLI formulation was vigorously stirred into a carbopol base before being characterized in vivo to investigate the permeation, bioavailability, and efficacy of VSD. The VLI gel enhanced the dermal permeation of VSD and, as a result, had 3.59 times higher bioavailability with excellent antitumor action as compared to oral VSD. In summary, as an alternative to oral administration for skin cancer treatment, invasomes are efficient carriers for delivering VSD and enhancing its transdermal flux into deep skin layers. [ABSTRACT FROM AUTHOR]