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Abstract Sickle cell disease (SCD) is a major public health burden worldwide with increasing morbidity and mortality. The study evaluates the risk factors associated with mortality in SCD patients, between the years 2006 and 2020 at three hospitals in Oman. The analysis includes clinical manifestations, haematological, biochemical, and radiological parameters, use of antibiotics, and blood and exchange transfusions. Our cohort included 123 patients (82 males, 41 females), with a median age of 27 (Interquartile Range 21–35 years). SCD related complications included acute chest syndrome (ACS) in 52.8%, splenic sequestration in 21.1%, right upper quadrant syndrome in 19.5%, more than > 6 VOC/year in 17.9%, and stroke in 13.8%. At the terminal admission, patients had cough, reduced O2 saturation, crepitation and fever in 24.4%, 49.6%, 53.6% and 68.3% respectively. Abnormal chest X-ray and chest CT scan were seen in 57.7%, and 76.4% respectively. Laboratory parameters showed a significant drop in hemoglobin (Hb) and platelet counts from baseline, with a significant rise in WBC, LDH and CRP from baseline (p

Abstract Background Newcastle Disease Virus (NDV) causes severe economic losses in the poultry industry worldwide. Hence, this study aimed to discover a novel bioactive antiviral agent for controlling NDV. Streptomyces misakiensis was isolated from Egyptian soil and its secondary metabolites were identified using infrared spectroscopy (IR), gas chromatography–mass spectrometry (GC–MS), and nuclear magnetic resonance (NMR) spectroscopy. The inhibitory activity of bioactive metabolite against NDV were examined. Three experimental groups of 10-day-old specific pathogen-free embryonated chicken eggs (SPF-ECEs), including the bioactive metabolite control group, NDV control positive group, and α-sitosterol and NDV mixture-treated group were inoculated. Results α-sitosterol (Ethyl-6-methylheptan-2-yl]-10,13-dimethyl-dodecahydro-1H-cyclopenta[a]phenanthren-3-ol), a secondary metabolite of S. misakiensis, completely inhibited hemagglutination (HA) activity of the NDV strain. The HA activity of the NDV strain was 8 log2 and 9 log2 for 0.5 and 0.75% RBCs, respectively. The NDV HA activity for the two concentrations of RBCs was significantly (P

Background: Natural colorants, including natural pigments, e.g., anthocyanins, carotenoids, and chlorophylls, in novel and attractive food matrixes have become a popular trend. They impart favorite colors to food products and provide significant therapeutic effects. This study is aimed at extracting and identifying some natural pigments from different plant sources and evaluating their ability as antibacterial, antioxidant, and anticancer activities. Methods: The anthocyanin-rich extract (ARE) is derived from three natural plant sources: pomegranate peel (Punica granatum), chili pepper fruit (Capsicum annuum), and Bougainvillea flowers. Bougainvillea spectabilis are analyzed for biochemical composition, as well as antioxidant, antibacterial, and anticancer activity, HPLC, DPPH, FRAP, disc diffusion assay, MIC, MTT, VEGFR‐2, and caspase-9 assays. Results: All three extracts had varying total phenolic contents, ranging from 14 to 466 mg GAE/g extract, where Punica granatum was the highest (466 mg GAE/g extract), followed by Bougainvillea spectabilis (180 mg GAE/g extract), and then Capsicum annuum (14 mg GAE/g extract). The antioxidant activity rose steadily with raising concentration. The ARE of pomegranate peels recorded highest value, followed by Bougainvillea flowers and chili pepper fruit. The MTT assay revealed an inhibitory action of the tested extracts on the proliferation of HCT-116, MCF-7, and HepG2 in a concentration-based manner. Gene expression of caspase-9 transcripts was considerably multiplied by the application of ARE of pomegranate peels. All the tested extracts inhibited VEGFR-2, and the inhibition (%) expanded gradually with increasing concentrations, achieving the highest value (80 %) at 10 μg/mL. The ARE of pomegranate peels scored highest antibacterial activity, followed by ARE of chili pepper fruit and Bougainvillea flowers. The inhibition zone diameter escalated gradually with rising concentrations of the tested samples. Conclusion: The AREs of the three studied plant sources can be used as multifunctional products with antioxidant, anticancer, and antibacterial activities that are natural, safe, and cheap.

Introduction: Increased Actin-like 6A (ACTL6A) expression is associated with various cancers, but its comprehensive investigation across different malignancies is lacking. We aimed to analyze ACTL6A as a potential oncogene and therapeutic target using bioinformatics tools.Methods: We comprehensively analyzed ACTL6A expression profiles across human malignancies, focusing on correlations with tumor grade, stage, metastasis, and patient survival. Genetic alterations were examined, and the epigenetic landscape of ACTL6A was assessed using rigorous methods. The impact of ACTL6A on immune cell infiltration in the tumor microenvironment was evaluated, along with molecular docking studies and machine learning models.Results: Our analysis revealed elevated ACTL6A expression in various tumors, correlating with poor prognostic indicators such as tumor grade, stage, metastasis, and patient survival. Genetic mutations and epigenetic modifications were identified, along with associations with immune cell infiltration and key cellular pathways. Machine learning models demonstrated ACTL6A's potential for cancer detection.Discussion: ACTL6A emerges as a promising diagnostic and therapeutic target in cancer, with implications for prognosis and therapy. Our study provides comprehensive insights into its carcinogenic actions, highlighting its potential as both a prognostic indicator and a target for anti-cancer therapy. This integrative approach enhances our understanding of ACTL6A's role in cancer pathogenesis and treatment.

Background and Objectives: Ventilator-associated pneumonia (VAP) is a common complication in critically ill patients receiving mechanical ventilation. The incidence rates of VAP vary, and it poses significant challenges due to microbial resistance and the potential for adverse outcomes. This study aims to explore the microbial profile of VAP and evaluate the utility of biomarkers and illness severity scores in predicting survival. Materials and Methods: A retrospective cohort study was conducted involving 130 patients diagnosed with VAP. Microbial analysis of bronchoalveolar lavage (BAL) fluid, as well as measurements of C-reactive protein (CRP) and procalcitonin (PCT) levels, were performed. Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation II (APACHE II) scores were calculated to assess illness severity. Statistical analyses were conducted to determine correlations and associations. Results: The study revealed that Klebsiella pneumoniae (K. pneumoniae) (50.7%) and Pseudomonas aeruginosa (P. aeruginosa) (27.69%) were the most identified microorganisms in VAP cases. SOFA (p-value < 0.0001) and APACHE II (p-value < 0.0001) scores were effective in assessing the severity of illness and predicting mortality in VAP patients. Additionally, our investigation highlighted the prognostic potential of CRP levels (odds ratio [OR]: 0.980, 95% confidence interval [CI] 0.968 to 0.992, p = 0.001). Elevated levels of CRP were associated with reduced survival probabilities in VAP patients. Conclusion: This study highlights the microbial profile of VAP and the importance of biomarkers and illness severity scores in predicting survival. Conclusions: The findings emphasize the need for appropriate management strategies to combat microbial resistance and improve outcomes in VAP patients.

The aim of this study was to assess L-carnitine’s effects on adult male rats’ lung damage brought on by amiodarone, which is a potent antiarrhythmic with limited clinical efficacy due to potentially life-threatening amiodarone-induced lung damage. Because of the resemblance among the structural abnormalities in rats’ lungs that follows amiodarone medication and pulmonary toxicity in human beings, this animal model may be an appropriate example for this disease entity. Amiodarone produced pulmonary toxicity in twenty-four healthy male albino rats (150–180 g) over a period of 6 weeks. Four groups of six rats each were established: control, sham, amiodarone, and L-carnitine plus amiodarone. Histological, ultrastructural, oxidative stress, and inflammatory markers were determined during a 6-week exposure experiment. Amiodarone-induced lung damage in rats may be brought on due to oxidative stress producing significant pulmonary cytotoxicity, as evidenced by the disruption of the mitochondrial structure, severe fibrosis, and inflammatory response of the lung tissue. Lungs already exposed to such harmful effects may be partially protected by the antioxidant L-carnitine. Biochemical markers of lung damage brought on by amiodarone include lung tissue levels of the enzyme’s catalase, superoxide dismutase, and reduced glutathione. The levels of lipid peroxides in lung tissue measured as malondialdehyde increased significantly upon exposure to amiodarone. In addition, the levels of tumor necrosis factor alpha were significantly elevated in response to amiodarone. The effect of L-carnitine on amiodarone-induced pulmonary toxicity was studied in rats. It is interesting to note that the intake of L-carnitine in rats treated with amiodarone partially restored the biochemical and histopathological alterations brought on by amiodarone to their original levels. Tumor necrosis factor alpha levels were significantly reduced upon L-carnitine exposure. These results suggest that L-carnitine can be used to treat amiodarone-induced pulmonary dysfunction.

Currently, doxorubicin (DOX) is one of the medications commonly used in chemotherapy to treat different types of tumors.Nonetheless, despite being effective in multiple tumors, yet its use is limited owing to its cytotoxic effects, the therapeutic use of DOX has been limited. This work aimed to explore whether curcumin (CMN) can prevents DOX-induced cardiotoxicity in rats. Four groups of rats were created, with the first functioning as a control, while the second group received CMN. DOX alone was administered to the third group, whereas CMN and DOX were administered to the fourth group. Lipid peroxidation assessed as Malondialdehyde (MDA), aspartate aminotransferase (AST), alanine aminotransferase (ALT), oxidative stress markers as catalase (CAT), superoxide dismutase (SOD), and inflammatory markers as tumor necrosis factor-alpha (TNF-α) in heart homogenates, each one was assessed. Heart specimens was investigated histologically and ultrastructurally. Increased, AST, and ALT serum levels, increased MDA levels, decreased SOD and CAT levels, and increased TNF-α concentrations in heart homogenates were all signs of DOX-induced myocardial injury. Histological and ultrastructural examinations revealed vacuoles and larger, swollen mitochondria in the cytoplasm. Furthermore, DOX caused significant changes in the myocardium, most notably nuclei disintegration, myofibrillar loss, and myocyte vacuolization. Using CMN with DOX reduced the harmful consequences of DOX on the myocardium by returning the increased AST and ALT levels to their original levels as compared to the control and reducing them. In cardiac tissue, CMN significantly increased the concentrations of SOD and CAT and significantly decreased the concentrations of MDA and TNF-α. Biochemical and histological studies have demonstrated that CMN has a heart-protective effect that might be related to its antioxidant and anti-inflammatory capabilities.

IntroductionPsoriasis and vitiligo are inflammatory autoimmune skin disorders with remarkable genetic involvement. Mannose-binding lectin (MBL) represents a significant immune molecule with one of its gene variants strongly linked to autoimmune diseases. Therefore, in this study, we investigated the role of the MBL variant, rs1800450, in psoriasis and vitiligo disease susceptibility.MethodsThe study comprised performing in silico analysis, performing an observational study regarding psoriasis patients, and performing an observational study regarding vitiligo patients. Various in silico tools were used to investigate the impact of the selected mutation on the function, stability, post-translational modifications (PTMs), and secondary structures of the protein. In addition, a total of 489 subjects were enrolled in this study, including their demographic and clinicopathological data. Genotyping analysis was performed using real-time PCR for the single nucleotide polymorphism (SNP) rs1800450 on codon 54 of the MBL gene, utilizing TaqMan genotyping technology. In addition, implications of the studied variant on disease susceptibility and various clinicopathological data were analyzed.ResultsComputational analysis demonstrated the anticipated effects of the mutation on MBL protein. Furthermore, regarding the observational studies, rs1800450 SNP on codon 54 displayed comparable results in our population relative to global frequencies reported via the 1,000 Genomes Project. This SNP showed no significant association with either psoriasis or vitiligo disease risk in all genetic association models. Furthermore, rs1800450 SNP did not significantly correlate with any of the demographic or clinicopathological features of both psoriasis and vitiligo.DiscussionOur findings highlighted that the rs1800450 SNP on the MBL2 gene has no role in the disease susceptibility to autoimmune skin diseases, such as psoriasis and vitiligo, among Egyptian patients. In addition, our analysis advocated the notion of the redundancy of MBL and revealed the lack of significant impact on both psoriasis and vitiligo disorders.

Groundwater, a primary source of freshwater on Earth, is rapidly declining due to natural and anthropogenic activities. This study aimed to investigate the spatial distribution of dissolved organic matter (DOM) and heavy metals (HMs) in two municipal groundwater networks (A and B) from tube wells to taps in an industrial city, Faisalabad. The results showed that parameters such as color, turbidity, pH, EC, TDS, Ca2+, Mg2+, CO32−, HCO3−, Cl−, CaCO3, Na+, and NO3− were within the permissible limits set by the World Health Organization (WHO) and Pakistan Environmental Quality Standards (PEQSs). However, parameters like DO and COD exceeded standard values along the routes. Odor, taste, temperature, BOD, NH4+, T. coli, and F. coli surpassed acceptable levels at the tap end of both networks. Fluorescence EEM-PARAFAC spectra were analyzed at an excitation wavelength of 220–500 nm and emission wavelength of 240–550 nm, revealing UVA-humic-like (C1–C2) and UVC-humic-like (C3) components in the DOM. Based on fluorescence intensity, DOM was dominated by C2 > C1 > C3 compounds in both networks. The mean concentrations of HMs, including Cu, Zn, and Fe, fell below the prescribed limits in both networks. However, concentrations of Pb (A: 0.015–0.028 mg/L), (B: 0.013–0.027 mg/L), and Cd (A: 0.004–0.006 mg/L), (B: 0.005–0.008 mg/L) exceeded permissible limits from tube wells to taps. Moreover, C1 demonstrated a significant positive correlation with Cd and Cu in networks A and B, respectively. Furthermore, C2 displayed a significant positive correlation with Cd in network A. This study concludes that the groundwater in both networks (A and B) is contaminated by agricultural runoff, industrial and sewage water, plumbing materials, and eroded pipelines. As a result, the water is unsafe for cooking and drinking, posing risks of kidney, lung, and bladder cancers. Therefore, this study urgently recommends pipeline reconstruction and the implementation of proper groundwater remediation approaches before these sources are used for drinking.

Replication Factor C Subunit 4 (RFC4), an oncogene implicated in many human cancers, has yet to be extensively studied in many cancer types to determine its expression patterns and tumor tissue function. Various bioinformatics tools were used to analyze RFC4 as a potential oncogene and therapeutic target across many cancers. We first examined RFC4 expression levels in several human tumor types to determine relationships with tumor grade, stage, metastasis, and patient survival. We also examined RFC4’s genetic changes, epigenetic methylation, and effect on tumor microenvironment (TME) immune cell infiltration. We also analyzed RFC4’s connections with immunological checkpoints to identify potential molecular pathways involved in carcinogenesis. Our findings show that RFC4 is upregulated in several tumor types and associated with poor prognoses in many human cancers. This study shows that RFC4 significantly affects the tumor immunological microenvironment, specifically immune cell populations. Finally, we screened for RFC4-inhibiting pharmacological compounds with anti-cancer potential. This study fully elucidates RFC4’s carcinogenic activities, emphasizing its potential as a prognostic biomarker and a target for anti-cancer therapy.

Background: The daily practice of urology includes managing patients with urolithiasis, and there are various methods for managing ureteral calculi. There are many techniques for fragmenting stones. The holmium: yttrium-aluminum-garnet [Ho: YAG] laser is often utilized in stone disintegration procedures.Aim of the work: This research compares the effectiveness of laser and pneumatic lithotripsy in treating patients with upper ureteric calculi regarding the percentage of patients who remain stone-free, hospital stays, surgical times, and complications.Patients and methods: Sixty individuals with upper ureteric calculus participated in this prospective comparative analysis. From February 2021 to March 2022, the patients were randomly divided into two groups [Laser Lithotripsy and Pneumatic Lithotripsy]. The main goals of both treatments were to break the stone into pieces smaller than 3 mm, which was confirmed by an X-ray [KUB] on the first post-operative day.Results: The study's eligibility criteria were met by 60 individuals with upper ureteric stones [30 in the pneumatic group and 30 in the laser group]. In laser lithotripsy, the immediately stone-free rate was 93.3 percent, while in pneumatic lithotripsy, it was 70.0 percent [p value 0.059]. Proximal migration was 6.7% in Laser Lithotripsy and 26.6% in Pneumatic Lithotripsy [p > 0.038]. Pneumatic lithotripsy had a substantially longer operating time than laser lithotripsy [27.83±6.11 min vs. 24.47±5.08 min; p=0.024]. There were no statistically substantial variations between the two groups regarding the patients' age, sex, stone size, length of hospitalization, and complications.Conclusion: Laser and pneumatic lithotripsy are safe and effective in the treatment of upper ureteric stone with few minor complications; however, laser lithotripsy has a better stone free rate, less operative time, less fluid irrigated and less upward stone migration than pneumatic lithotripsy.

Interleukin-1-receptor-associated kinase 4 (IRAK4) possesses a crucial function in the toll-like receptor (TLR) signaling pathway, and the dysfunction of this molecule could lead to various infectious and immune-related diseases in addition to cancers. IRAK4 genetic variants have been linked to various types of diseases. Therefore, we conducted a comprehensive analysis to recognize the missense variants with the most damaging impacts on IRAK4 with the employment of diverse bioinformatics tools to study single-nucleotide polymorphisms’ effects on function, stability, secondary structures, and 3D structure. The residues’ location on the protein domain and their conservation status were investigated as well. Moreover, docking tools along with structural biology were engaged in analyzing the SNPs’ effects on one of the developed IRAK4 inhibitors. By analyzing IRAK4 gene SNPs, the analysis distinguished ten variants as the most detrimental missense variants. All variants were situated in highly conserved positions on an important protein domain. L318S and L318F mutations were linked to changes in IRAK4 secondary structures. Eight SNPs were revealed to have a decreasing effect on the stability of IRAK4 via both I-Mutant 2.0 and Mu-Pro tools, while Mu-Pro tool identified a decreasing effect for the G198E SNP. In addition, detrimental effects on the 3D structure of IRAK4 were also discovered for the selected variants. Molecular modeling studies highlighted the detrimental impact of these identified SNP mutant residues on the druggability of the IRAK4 ATP-binding site towards the known target inhibitor, HG-12-6, as compared to the native protein. The loss of important ligand residue-wise contacts, altered protein global flexibility, increased steric clashes, and even electronic penalties at the ligand–binding site interfaces were all suggested to be associated with SNP models for hampering the HG-12-6 affinity towards IRAK4 target protein. This given model lays the foundation for the better prediction of various disorders relevant to IRAK4 malfunction and sheds light on the impact of deleterious IRAK4 variants on IRAK4 inhibitor efficacy.

Urinary tract infections (UTIs) are healthcare problems that commonly involve bacterial and, in some rare instances, fungal or viral infections. The irrational prescription and use of antibiotics in UTI treatment have led to an increase in antibiotic resistance. Urine samples (145) were collected from male and female patients from Lower Dir, Khyber Pakhtunkhwa (KP), Pakistan. Biochemical analyses were carried out to identify uropathogens. Molecular analysis for the identification of 16S ribosomal RNA in samples was performed via Sanger sequencing. Evolutionary linkage was determined using Molecular Evolutionary Genetics Analysis-7 (MEGA-7). The study observed significant growth in 52% of the samples (83/145). Gram-negative bacteria were identified in 85.5% of samples, while Gram-positive bacteria were reported in 14.5%. The UTI prevalence was 67.5% in females and 32.5% in males. The most prevalent uropathogenic bacteria were Klebsiella pneumoniae (39.7%, 33/83), followed by Escherichia coli (27.7%, 23/83), Pseudomonas aeruginosa (10.8%, 9/83), Staphylococcus aureus (9.6%, 8/83), Proteus mirabilis (7.2%, 6/83) and Staphylococcus saprophyticus (4.8%, 4/83). Phylogenetic analysis was performed using the neighbor-joining method, further confirming the relation of the isolates in our study with previously reported uropathogenic isolates. Antibiotic susceptibility tests identified K. pneumonia as being sensitive to imipenem (100%) and fosfomycin (78.7%) and resistant to cefuroxime (100%) and ciprofloxacin (94%). Similarly, E. coli showed high susceptibility to imipenem (100%), fosfomycin (78.2%) and nitrofurantoin (78.2%), and resistance to ciprofloxacin (100%) and cefuroxime (100%). Imipenem was identified as the most effective antibiotic, while cefuroxime and ciprofloxacin were the least. The phylogenetic tree analysis indicated that K. pneumoniae, E. coli, P. aeruginosa, S. aureus and P. mirabilis clustered with each other and the reference sequences, indicating high similarity (based on 16S rRNA sequencing). It can be concluded that genetically varied uropathogenic organisms are commonly present within the KP population. Our findings demonstrate the need to optimize antibiotic use in treating UTIs and the prevention of antibiotic resistance in the KP population.

In severe cases of sepsis, endotoxin-induced cardiomyopathy can cause major damage to the heart. This study was designed to see if Vitamin C (Vit C) could prevent lipopolysaccharide-induced heart damage. Eighteen Sprague Dawley male rats (n = 6) were divided into three groups. Rats received 0.5 mL saline by oral gavage in addition to a standard diet (Control group), rats received one dose of endotoxin on day 15 (lipopolysaccharide) (LPS) (6 mg/kg), which produced endotoxemia (Endotoxin group), and rats that received 500 mg/Kg BW of Vit C by oral gavage for 15 days before LPS administration (Endotoxin plus Vit C group). In all groups, blood and tissue samples were collected on day 15, six hours after LPS administration, for histopathological and biochemical analysis. The LPS injection lowered superoxide dismutase (SOD) levels and increased malondialdehyde in tissues compared with a control group. Furthermore, the endotoxin group showed elevated inflammatory biomarkers, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Both light and electron microscopy showed that the endotoxic-treated group’s cardiomyocytes, intercalated disks, mitochondria, and endothelial cells were damaged. In endotoxemic rats, Vit C pretreatment significantly reduced MDA levels and restored SOD activity, minimized biomarkers of inflammation, and mitigated cardiomyocyte damage. In conclusion: Vit C protects against endotoxin-induced cardiomyopathy by inhibiting oxidative stress cytokines.

Hepatocellular carcinoma (HCC) is the most common form of malignancy in the liver. Autophagy was found to have a significant effect in controlling HCC. Anthocyanins, which are naturally occurring pigments in a variety of fruits and vegetables, have been thoroughly documented to be involved in a variety of bioactive activities and are widely employed for their antioxidant capabilities. Cyanidin-3-glucoside (C3G) extracted from Morus alba L. has promising antioxidant and anti-tumour activities. The current study aims to examine the protective action of C3G against hepatocellular carcinoma through the investigation of the autophagy protein ATG16L1 expression along with its related RNA molecules (hsa_circ_0001345 and miRNA106b) in Wistar rats. In vivo precancerous lesions (PCL) were induced using diethylnitrosamine (DEN) and acetamidofluorene (2-AAF). Rats were treated with C3G (10, 15, and 20 mg/kg; 4 times weekly) for 112 days (16 weeks). Liver function tests, alfa fetoprotein, ATG16L1 expression, hsa_circ_0001345, and miRNA106b differential expression were examined. Liver sections were examined by histological and immunohistochemical approaches. The current study’s findings indicated that C3G administration protects against the negative effects of DEN-2-AAF on liver functions and liver histopathological sections, which nominated C3G as a potential prophylactic agent against HCC.

Introduction: Several recent studies pointed out that chromodomain-helicase-DNA-binding protein 1-like (CHD1L) is a putative oncogene in many human tumors. However, up to date, there is no pan-cancer analysis performed to study the different aspects of this gene expression and behavior in tumor tissues.Methods: Here, we applied several bioinformatics tools to make a comprehensive analysis for CHD1L. Firstly we assessed the expression of CHD1L in several types of human tumors and tried to correlate that with the stage and grade of the analyzed tumors. Following that, we performed a survival analysis to study the correlation between CHD1L upregulation in tumors and the clinical outcome. Additionally, we investigated the mutation forms, the correlation with several immune cell infiltration, and the potential molecular mechanisms of CHD1L in the tumor tissue.Result and discussion: The results demonstrated that CHD1L is a highly expressed gene across several types of tumors and that was correlated with a poor prognosis for most cancer patients. Moreover, it was found that CHD1L affects the tumor immune microenvironment by influencing the infiltration level of several immune cells. Collectively, the current study provides a comprehensive overview of the oncogenic roles of CHD1L where our results nominate CHD1L as a potential prognostic biomarker and target for antitumor therapy development.

An abattoir survey was conducted from October 2020 to September 2021 to identify the primary reasons for offal and carcass condemnation of slaughtered animals in Dakahlia province, Egypt, as well as to estimate their economic loss. During the survey, 643 animals (441 cattle, 178 buffalos, 19 camels, 4 sheep, and one goat) were submitted for antemortem and postmortem inspection. The results of both inspections were collected, analyzed, and the total economic loss was estimated by adding the condemnation of offal and carcasses over a twelve-month period. Retail prices for offal (liver, lung, heart, and tongue) and carcass prices per kg were obtained from local markets. Out of 643 animals slaughtered, 2 (0.31%) were totally condemned. In addition, postmortem inspection revealed that 217 (33.74%) livers, 158 (24.57%) lungs, 5 (0.78%) hearts, 14 (2.18%) heads, and 11(1.71%) tongues were condemned. Offal were condemned mainly due to pneumonia, fascioliasis, telangiectiasis, necrosis, and hydatidosis, whereas carcasses were rejected due to generalized tuberculosis. According to this study, the financial loss at the abattoir owing to carcass and organ condemnations was 244066 Egyptian Pounds over a twelve-month period (15746 USD). The incidence of meat rejection and subsequent financial loss was high compared to the amount of local revenue. The current study concluded that bacterial and parasitic diseases are still prevalent and cause significant economic damage in Dakahlia province, Egypt. This abattoir survey offered regional information on the principal reasons for carcass and organ condemnation in slaughtered animals, as well as an estimate of the direct economic consequences. Furthermore, the findings of the current work underlined the importance of developing an efficient monitoring system for meat condemnation and enforcing animal health strategies in Egypt.

Background: Mammalian WD-repeat protein 12 (WDR12), a family member of proteins containing repeats of tryptophan-aspartic acid (WD), is a potential homolog of yeast Ytm1p and consists of seven repeats of WD.Aim of the study: This study aims to investigate the potential oncogenic effects of WDR12 in various human malignancies throughout a pan-cancer analysis that has been carried out to examine the various patterns in which this gene is expressed and behaves in tumor tissues.Methods: Herein, we used The Cancer Genome Atlas (TCGA) and various computational tools to explore expression profiles, prognostic relevance, genetic mutations, immune cell infiltration, as well as the functional characteristics of WDR12 in multiple human cancers.Results: We found that WDR12 was inconsistently expressed in various cancers and that variations in WDR12 expression predicted survival consequences for cancer patients. Furthermore, we observed a significant correlation between WDR12 gene mutation levels and the prognosis of some tumors. Furthermore, significant correlations were found between WDR12 expression patterns and cancer-associated fibroblast (CAF) infiltration, myeloid-derived suppressor cells (MDSCs), tumor mutation burden, microsatellite instability and immunoregulators. Ultimately, pathway enrichment analysis revealed that WDR12-related pathways are involved in carcinogenesis.Conclusions: The findings of our study are stisfactory, demonstrating that WDR12 could serve as a promising reliable prognostic biomarker, as well as a therapeutic target for novel cancer therapeutic approaches.

Cyclin dependent kinase inhibitor 2A (CDKN2A) is a well-known tumor suppressor gene as it functions as a cell cycle regulator. While several reports correlate the malfunction of CDKN2A with the initiation and progression of several types of human tumors, there is a lack of a comprehensive study that analyzes the potential effect of CDKN2A genetic alterations on the human immune components and the consequences of that effect on tumor progression and patient survival in a pan-cancer model. The first stage of the current study was the analysis of CDKN2A differential expression in tumor tissues and the corresponding normal ones and correlating that with tumor stage, grade, metastasis, and clinical outcome. Next, a detailed profile of CDKN2A genetic alteration under tumor conditions was described and assessed for its effect on the status of different human immune components. CDKN2A was found to be upregulated in cancerous tissues versus normal ones and that predicted the progression of tumor stage, grade, and metastasis in addition to poor prognosis under different forms of tumors. Additionally, CDKN2A experienced different forms of genetic alteration under tumor conditions, a characteristic that influenced the infiltration and the status of CD8, the chemokine CCL4, and the chemokine receptor CCR6. Collectively, the current study demonstrates the potential employment of CDKN2A genetic alteration as a prognostic and immunological biomarker under several types of human cancers.

Marburg virus (MARV) is one of the most harmful zoonotic viruses with deadly effects on both humans and nonhuman primates. Because of its severe outbreaks with a high rate of fatality, the world health organization put it as a risk group 4 pathogen and focused on the urgent need for the development of effective solutions against that virus. However, up to date, there is no effective vaccine against MARV in the market. In the current study, the complete proteome of MARV (seven proteins) was analyzed for the antigenicity score and the virulence or physiological role of each protein where we nominated envelope glycoprotein (Gp), Transcriptional activator (VP30), and membrane-associated protein (VP24) as the candidates for epitope prediction. Following that, a vaccine construct was designed based on CTL, HTL, and BCL epitopes of the selected protein candidates and to finalize the vaccine construct, several amino acid linkers, β-defensin adjuvant, and PADRE peptides were incorporated. The generated potential vaccine was assessed computationally for several properties such as antigenicity, allergenicity, stability, and other structural features where the outcomes of these assessments nominated this potential vaccine to be validated for its binding affinity with two molecular targets TLR-8 and TLR-4. The binding score and the stability of the vaccine-receptor complex, which was deeply studied through molecular docking-coupled dynamics simulation, supported the selection of our designed vaccine as a putative solution for MARV that should be validated through future wet-lab experiments. Here, we describe the computational approach for designing and analysis of this potential vaccine.

BackgroundA deep understanding of the causes of liability to SARS-CoV-2 is essential to develop new diagnostic tests and therapeutics against this serious virus in order to overcome this pandemic completely. In the light of the discovered role of antimicrobial peptides [such as human b-defensin-2 (hBD-2) and cathelicidin LL-37] in the defense against SARS-CoV-2, it became important to identify the damaging missense mutations in the genes of these molecules and study their role in the pathogenesis of COVID-19.MethodsWe conducted a comprehensive analysis with multiple in silico approaches to identify the damaging missense SNPs for hBD-2 and LL-37; moreover, we applied docking methods and molecular dynamics analysis to study the impact of the filtered mutations.ResultsThe comprehensive analysis reveals the presence of three damaging SNPs in hBD-2; these SNPs were predicted to decrease the stability of hBD-2 with a damaging impact on hBD-2 structure as well. G51D and C53G mutations were located in highly conserved positions and were associated with differences in the secondary structures of hBD-2. Docking-coupled molecular dynamics simulation analysis revealed compromised binding affinity for hBD-2 SNPs towards the SARS-CoV-2 spike domain. Different protein–protein binding profiles for hBD-2 SNPs, in relation to their native form, were guided through residue-wise levels and differential adopted conformation/orientation.ConclusionsThe presented model paves the way for identifying patients prone to COVID-19 in a way that would guide the personalization of both the diagnostic and management protocols for this serious disease.

The present study was conducted to evaluate the microbiological status of rabbit carcasses marketed in Zagazig City, Sharkia province, Egypt. Eighty random samples of fresh rabbit meat cuts representing shoulder, loin, ribs, and thigh regions (20 of each) were obtained from different rabbit markets in Zagazig City during 2022. Aerobic plate count (APC), Enterobacteriaceae, total mould and yeast counts were determined in the collected samples, as well as the isolation and identification of E. coli and Salmonella spp. The results showed that the mean values of APC and Enterobacteriaceae were 1.1x106 and 4.7x104 CFU/g for shoulders, 9.6x105 and 5.7x104 CFU/g for ribs, 1.0x106 and 5.1x104 CFU/g for loins, 1.2x106 and 6.0x104 CFU/g for thigh samples, respectively. Moreover, the total mould and yeast count ranged from 2.6x104 to 1.9x105 with mean values of 9.7x104 ± 1.1x104, 8.2x104 ± 9.9x103, 9.5x104 ± 1.4x104 and 9.8x104 ± 8.5x103 CFU/g in the of examined rabbit meat samples from shoulder, ribs, loin, and thigh regions, respectively. In terms of food poisoning bacteria, 6 (30 %), 7 (35 %), 6 (30 %) and 4 (20 %) out of 20 rabbit cuts tested positive for Salmonellae in the shoulder, ribs loin, and thigh regions, respectively. However, E. coli was found in 18 (90%), 16 (80%), 15 (75%) and 19 (95%) of the examined rabbit meat samples, respectively. The obtained results suggested that fresh rabbit meat cuts may carry numerus microorganisms from different sources, emphasizing the importance of stringent sanitary precautions during the slaughtering, handling and cooking procedures.

Emerging research findings have shown that a centrosomal protein (CEP55) is a potential oncogene in numerous human malignancies. Nevertheless, no pan-cancer analysis has been conducted to investigate the various aspects and behavior of this oncogene in different human cancerous tissues. Numerous databases were investigated to conduct a detailed analysis of CEP55. Initially, we evaluated the expression of CEP55 in several types of cancers and attempted to find the correlation between that and the stage of the examined malignancies. Then, we conducted a survival analysis to determine the relationship between CEP55 overexpression in malignancies and the patient’s survival. Furthermore, we examined the genetic alteration forms and the methylation status of this oncogene. Additionally, the interference of CEP55 expression with immune cell infiltration, the response to various chemotherapeutic agents, and the putative molecular mechanism of CEP55 in tumorigenesis were investigated. The current study found that CEP55 was upregulated in cancerous tissues versus normal controls where this upregulation was correlated with a poor prognosis in multiple forms of human cancers. Additionally, it influenced the level of different immune cell infiltration and several chemokines levels in the tumor microenvironment in addition to the response to several antitumor drugs. Herein, we provide an in-depth understanding of the oncogenic activities of CEP55, identifying it as a possible predictive marker as well as a specific target for developing anticancer therapies.

Epithelial cell transforming 2 (ECT2) is a potential oncogene and a number of recent studies have correlated it with the progression of several human cancers. Despite this elevated attention for ECT2 in oncology-related reports, there is no collective study to combine and integrate the expression and oncogenic behavior of ECT2 in a panel of human cancers. The current study started with a differential expression analysis of ECT2 in cancerous versus normal tissue. Following that, the study asked for the correlation between ECT2 upregulation and tumor stage, grade, and metastasis, along with its effect on patient survival. Moreover, the methylation and phosphorylation status of ECT2 in tumor versus normal tissue was assessed, in addition to the investigation of the ECT2 effect on the immune cell infiltration in the tumor microenvironment. The current study revealed that ECT2 was upregulated as mRNA and protein levels in a list of human tumors, a feature that allowed for the increased filtration of myeloid-derived suppressor cells (MDSC) and decreased the level of natural killer T (NKT) cells, which ultimately led to a poor prognosis survival. Lastly, we screened for several drugs that could inhibit ECT2 and act as antitumor agents. Collectively, this study nominated ECT2 as a prognostic and immunological biomarker, with reported inhibitors that represent potential antitumor drugs.

Decreasing male fertility encouraged the investigators to innovate accurate diagnostic non-invasive methods for detection of changes in the testicular parenchyma. Ultrasonography (US) has the potential to be used in this manner for decades, but magnetic resonance imaging (MRI) is still of limited application in animals for this purpose. The current study was designed to describe appearances and quantitative MRI attributes of the normal testes, epididymis besides angiography of testicular artery in camels. About 30 apparently healthy male dromedary camels aged 8–14 years were slaughtered during the rutting season. Immediately after slaughtering, the male gonads (n = 30 pairs of testicles and epididymis) were subjected to morphometric evaluation using a Vernier caliper and ultrasound scanning. Epididymial sperms were evaluated for motility, vitality and abnormality. MRI was performed for testes (n=16) by using a 1.5T Excite-II MRI apparatus of Sigma. Radiography and angioarchitecture of testicular artery (n=24) were done. Camel testicular length, width, and depth showed non-significant differences between a Vernier caliper or sonar. The MRI results revealed that both the testis and epididymis have homogenously intermediate signal (T1) and testes have hyperintense signal, with slightly lower signal in the epididymis (T2). In conclusion, both the ultrasonography and MRI techniques, with each respective computer-assisted imaging, could be used to detect the histomorphological changes of the camels' testicles. However, US imaging remains the first diagnostic technique for evaluating the reproductive health in men for its lower cost and accuracy. MRI is beneficial when the sonograms are inconclusive and/or equivocal. It shows the examined tissues in greater anatomical details compared to ultrasonography. Further studies are needed to compare between characteristics of US and MRI of normal testes and epididymis with testicular artery angiography in living camel during rut season and non-rut season and between normal healthy and affected diseased genitalia.

Objectives: The primary purpose of the recent experiment was to scrutinize the dissimilarity between single and multiple exposures by electrotherapeutic modalities to determine the development of Gram-positive and Gram negative bacteria spectrum. Material and methods: Bacterial strains employed in this study were Gram-negative bacteria such as Pseudomonas aeruginosa, Escherichia coli, and Klebsiella pneumonae and Gram-positive bacteria such as Staphylococcus aureus, Staphylococcus saprophyticus and Streptococcus pyogenes. Fluence for Low level laser therapy (LLLT) (810 nm) was 40 J/cm2 for 80 s, for microwave (MWD) a dosage of 100-Watt with duration of 5 min and for magnetic field therapy (MT) duration of 30 min with 100% intensity was used. Results: Repeated Measures of analysis of variances (RANOVA) for within-subject effects was used to detect a global significant change within the means at dissimilar time points. The experiments of within-subjects revealed a significant difference within groups, df of (3, 40), F value of 39.38 and a p value less than 0.001, representing a significant variation between the three groups between pre and post exposures. There was a significant variation between single exposure and multiple exposures in the experimental sample’s pre-post between the four groups with df (1, 40) f value of 2943.69 and p value less than 0.001. Scanning and Transmission electron microscopy images were also taken into account to determine the extent of damage caused to the bacterial cells surface topography in Gram negative and Gram positive spectrums. Conclusion: The study demonstrated that single high exposure with the LLLT appears to have the most emphatic effect followed by exposure by MWD and MT.

Background: Bisphenol A (BPA) is an environmental contaminant that can induce deleterious organ effects. Human Cytochrome P450 CYP2C9 enzyme belongs to the essential xenobiotic-metabolizing enzymes, producing ROS as a byproduct. Astaxanthin (ATX) is a powerful antioxidant that protects organs and tissues from the damaging effects of oxidative stress caused by various diseases. Aim of the study: This study investigated the possible protective impacts of ATX against BPA-induced nephrotoxicity and its underlying mechanism. Materials and methods: Kidney tissues were isolated and examined microscopically from control, protected, and unprotected groups of rats to examine the potential protective effect of ATX against nephrotoxicity. Moreover, a molecular dynamic (MD) simulation was conducted to predict the performance of ATX upon binding to the active site of P450 CYP2C9 protein receptor as a potential mechanism of ATX protective effect. Results: Implemented computational methods revealed the possible underlying mechanism of ATX protection; the protective impact of ATX is mediated by inhibiting P450 CYP2C9 through binding to its dimeric state where the RMSF value for apo-protein and ATX-complex system were 5.720.57 and 1.040.41, respectively, implicating the ATX-complex system to have lesser variance in its residues, leading to the prevention of ROS excess production, maintaining the oxidant-antioxidant balance and re-establishing the proper mitochondrial functionality. Furthermore, the experimental methods validated in silico outcomes and revealed that ATX therapy effectively restored the typical histological architecture of pathological kidney tissues. Conclusions: ATX prevents BPA-induced nephrotoxicity by controlling oxidative imbalance and reversing mitochondrial dysfunction. These outcomes shed new light on the appropriate use of ATX as a treatment or prophylactic agent for these severe conditions.

Lower extremity arterial disease (LEAD) is a major risk factor for amputation in diabetic patients. The advanced glycation end products (AGEs)/endothelin-1 (ET-1)/nitric oxide synthase (NOS) axis-mediated femoral artery injury with and without metformin has not been previously investigated. Type 2 diabetes mellitus (T2DM) was established in rats, with another group of rats treated for two weeks with 200 mg/kg metformin, before being induced with T2DM. The latter cohort were continued on metformin until they were sacrificed at week 12. Femoral artery injury was established in the diabetic group as demonstrated by substantial alterations to the femoral artery ultrastructure, which importantly were ameliorated by metformin. In addition, diabetes caused a significant (p < 0.0001) upregulation of vascular tissue levels of AGEs, ET-1, and iNOS, as well as high blood levels of glycated haemoglobin, TNF-α, and dyslipidemia. All of these parameters were also significantly inhibited by metformin. Moreover, metformin treatment augmented arterial eNOS expression which had been inhibited by diabetes progression. Furthermore, a significant correlation was observed between femoral artery endothelial tissue damage and glycemia, AGEs, ET-1, TNF-α, and dyslipidemia. Thus, in a rat model of T2DM-induced LEAD, an association between femoral artery tissue damage and the AGEs/ET-1/inflammation/NOS/dyslipidemia axis was demonstrated, with metformin treatment demonstrating beneficial vascular protective effects.

The emerging concept of cancer stem cells (CSCs) as the key driver behind carcinogenesis, progression, and diversity has displaced the prior model of a tumor composed of cells with similar subsequently acquired mutations and an equivalent capacity for renewal, invasion, and metastasis. This significant change has shifted the research focus toward targeting CSCs to eradicate cancer. CSCs may be characterized using cell surface markers. They are defined by their capacity to self-renew and differentiate, resist conventional therapies, and generate new tumors following repeated transplantation in xenografted mice. CSCs’ functional capabilities are governed by various intracellular and extracellular variables such as pluripotency-related transcription factors, internal signaling pathways, and external stimuli. Numerous natural compounds and synthetic chemicals have been investigated for their ability to disrupt these regulatory components and inhibit stemness and terminal differentiation in CSCs, hence achieving clinical implications. However, no cancer treatment focuses on the biological consequences of these drugs on CSCs, and their functions have been established. This article provides a biomedical discussion of cancer at the time along with an overview of CSCs and their origin, features, characterization, isolation techniques, signaling pathways, and novel targeted therapeutic approaches. Additionally, we highlighted the factors endorsed as controlling or helping to promote stemness in CSCs. Our objective was to encourage future studies on these prospective treatments to develop a framework for their application as single or combined therapeutics to eradicate various forms of cancer.

Escherichia coli (E. coli) is a Gram-negative bacterium that belongs to the family Enterobacteriaceae. While E. coli can stay as an innocuous resident in the digestive tract, it can cause a group of symptoms ranging from diarrhea to live threatening complications. Due to the increased rate of antibiotic resistance worldwide, the development of an effective vaccine against E. coli pathotypes is a major health priority. In this study, a reverse vaccinology approach along with immunoinformatics has been applied for the detection of potential antigens to develop an effective vaccine. Based on our screening of 5,155 proteins, we identified lipopolysaccharide assembly protein (LptD) and outer membrane protein assembly factor (BamA) as vaccine candidates for the current study. The conservancy of these proteins in the main E. coli pathotypes was assessed through BLASTp to make sure that the designed vaccine will be protective against major E. coli pathotypes. The multitope vaccine was constructed using cytotoxic T lymphocyte (CTL), helper T lymphocyte (HTL), and B cell lymphocyte (BCL) epitopes with suitable linkers and adjuvant. Following that, it was analyzed computationally where it was found to be antigenic, soluble, stable, and non-allergen. Additionally, the adopted docking study, as well as all-atom molecular dynamics simulation, illustrated the promising predicted affinity and free binding energy of this constructed vaccine against the human Toll-like receptor-4 (hTLR-4) dimeric state. In this regard, wet lab studies are required to prove the efficacy of the potential vaccine construct that demonstrated promising results through computational validation.

إن التجريب عملية فنية فكرية إبداعية خلاقة تحقق معرفة أرقى، متجددة غالباً ما تحمل صفات المغامرة الإنسانية وخصائصها، والقدرة على فض المجهول واستيعاب الجديد، وجعل من قصيدة النثر العراقية شعلة إبداعية تساهم في خلق تجربة خلاقة تفيد المجتمع، وتتفاعل مع الحياة اليومية. ويتسم التجريب بالمقصدية، للولوج إلى عالم جديد حداثوي يتعصرن مع استمرار الحياة، ولا يستطيع أن يخوض مضماره الهاوي أو المبتدئ ؛ أو المتشعرن، إلا من احكمته الخبرة وهذبته الموهبة الشعرية التي تمتد لسنين طويلة، وارتشف من منابع الطبع منذ نعومة أظفاره بعيداً عن التصنع. ويتأطر ويضع قوانينه يوماً بعد الآخر، ويرتقي لينظم نفسه، محاولاً الخروج عن النموذج الثابت متجاوزاً الأعمال التقليدية، ويبحث عن سبل الانفتاح، وقد ينسلخ في بعض الأحيان عن كل موروث أدبي، كما تجلت عوامله في قصيدة النثر العراقية بعد عام 2003م.

Cystic echinococcosis (CE), or hydatid cyst disease (HCD), is a zoonosis of significant importance caused by the cestode of Echinococcus granulosus sensu lato (s. l.) that affects mainly nomadic populations and has substantial economic consequences. Due to the 76% rural and nomadic population, Baluchistan is a highly endemic region in Pakistan for CE; however, it has not yet been investigated for CE. For this purpose, this study was carried out to investigate the molecular epidemiology of CE in this region. In total, 23 human hydatid cyst samples were collected from tertiary health care units in Baluchistan and processed for DNA extraction, which was then followed by sequencing of the cox1 mitochondrial gene of all 23 collected samples, genotyping, and phylogenetic and haplotype analysis. Most subjects were livestock owners (39.13%) in rural settings (73.91%). Most patients (73.19%) were pet owners (dogs) and used water from open sources for drinking. The liver was the most affected organ (52.17%), followed by the lungs (17.39%). Sequence analysis based on the cox1 gene revealed that EG genotype 1 (G1) was the most prevalent (56.52%), followed by G3 (34.78%), while some samples (8.7%) were identified as the Echinococcus canadensis (G6/7) genotype. A total of five haplotypes were detected with high haplotype diversity (0.80) and low nucleotide diversity (0.033). Phylogenetic analysis revealed two diverse sub-clades, each of G1 and G3 isolates from Baluchistan, that were evolutionarily related to previously reported G1 and G3 isolates from Pakistan and China. On the other hand, the G6/7 isolates of this study were evolutionarily identical to the already reported G6/7 isolates from Pakistan, Turkey, and Kazakhstan. This study concludes that diverse G1 and G3 EG isolates are present in this part of Pakistan, while the G6/G7 genotype was reported for the first time from Baluchistan.

Syphilis, a sexually transmitted infection, is a deadly disease caused by Treponema pallidum. It is a Gram-negative spirochete that can infect nearly every organ of the human body. It can be transmitted both sexually and perinatally. Since syphilis is the second most fatal sexually transmitted disease after AIDS, an efficient vaccine candidate is needed to establish long-term protection against infections by T. pallidum. This study used reverse-vaccinology-based immunoinformatic pathway subtractive proteomics to find the best antigenic proteins for multi-epitope vaccine production. Six essential virulent and antigenic proteins were identified, including the membrane lipoprotein TpN32 (UniProt ID: O07950), DNA translocase FtsK (UniProt ID: O83964), Protein Soj homolog (UniProt ID: O83296), site-determining protein (UniProt ID: F7IVD2), ABC transporter, ATP-binding protein (UniProt ID: O83930), and Sugar ABC superfamily ATP-binding cassette transporter, ABC protein (UniProt ID: O83782). We found that the multiepitope subunit vaccine consisting of 4 CTL, 4 HTL, and 11 B-cell epitopes mixed with the adjuvant TLR-2 agonist ESAT6 has potent antigenic characteristics and does not induce an allergic response. Before being docked at Toll-like receptors 2 and 4, the developed vaccine was modeled, improved, and validated. Docking studies revealed significant binding interactions, whereas molecular dynamics simulations demonstrated its stability. Furthermore, the immune system simulation indicated significant and long-lasting immunological responses. The vaccine was then reverse-transcribed into a DNA sequence and cloned into the pET28a (+) vector to validate translational activity as well as the microbial production process. The vaccine developed in this study requires further scientific consensus before it can be used against T. pallidum to confirm its safety and efficacy.

The chance of survival rate and autophagy of smooth muscle cells under calcium stress were drastically improved with a prolonged inclusion of Lycopene in the media. The results showed an improved viability from 41% to 69% and a reduction in overall autophagic bodies from 7% to 3%, which was well in agreement with the LC3II and III mRNA levels. However, the proliferation was slow compared to the controls. The fall in the major inflammatory marker TNF-α and improved antioxidant enzyme GPx were regarded as significant restoration markers of cell survival. The reactive oxygen species (ROS) were reduced from 8 fold to 3 fold post addition of lycopene for 24 h. Further, the docking studies revealed binding of lycopene molecules with 7SK snRNA at 7.6 kcal/mol docking energy with 300 ns stability under physiological conditions. Together, these results suggest that Lycopene administration during ischemic heart disease might improve the functions of the smooth muscle cells and 7SK snRNA might be involved in the binding of lycopene and its antioxidant protective effects.

Several recent studies have pointed out that arc GTPase activating protein 1 (RACGAP1) is a putative oncogene in many human tumors. However, to date, no pan-cancer analysis has been performed to study the different aspects of this gene expression and behavior in tumor tissues. Here, we applied several bioinformatics tools to perform a comprehensive analysis for RACGAP1. First, we assessed the expression of RACGAP1 in several types of human tumors and tried to correlate that with the stage of the tumors analyzed. We then performed a survival analysis to study the correlation between RACGAP1 upregulation in tumors and the clinical outcome. Additionally, we investigated the mutation forms, the correlation with several immune cell infiltration, the phosphorylation status of the interested protein in normal and tumor tissues, and the potential molecular mechanisms of RACGAP1 in cancerous tissue. The results demonstrated that RACGAP1, a highly expressed gene across several types of tumors, correlated with a poor prognosis in several types of human cancers. Moreover, it was found that RACGAP1 affects the tumor immune microenvironment by influencing the infiltration level of several immune cells. Collectively, the current study provides a comprehensive overview of the oncogenic roles of RACGAP1, where our results nominate it as a potential prognostic biomarker and a target for antitumor therapy development.

Vaccines against acute respiratory syndrome Coronavirus 2(SARS-CoV2) are critical weapons to control the spread of the deadly Coronavirus 2019(COVId-19) virus worldwide. Although these vaccines are generally safe, their widespread use has produced reports of rare complications, including vaccine-induced immune thrombotic thrombocytopenia (VIITT), particularly in connection with ChAdOx1 nCov-19. We have identified three cases of sickle cell disease (SCD) experiencing a severe vaso-occlusive crisis (VOC) shortly after the vaccine. Despite being stable for a long time, they had fever with tachycardia, along with a significant rise in WBC, liver enzymes, particularly alkaline phosphate, with a remarkable drop in hemoglobin, and platelets and one of them probably had fatal TTP like syndrome. Given these findings, physicians and patients should exercise caution when taking this type of vaccine and be aware of these safety concerns.

مما لا ريب فيه، أن القرن الماضي كان ولوداً بالنظريات والمناهج والرؤى الأدبية التي باتت موضوعاً للبحث والدراسة لما لها من أهمية لدى الأدباء والنقاد العرب، ففي منتصف العقد الثاني من القرن المنصرم، ولد المعادل الموضوعي على يد الناقد اليوت ؛ لكن ما يلفت النظر أن هذه الولادة كانت عسيرة، فلم يأخذ المعادل حيزه الحقيقي في الأدب، لما لأثره في تحديد معنى الإحساس والتصور الذي بني عليه الأدب ؛ فبات مضطرباً لكثرة المناهج والمصطلحات آنذاك، وبعدها لم يُفهم بصورة صحيحة، إذ اخذ كلٌ يفسره بحسب أهوائه، فضلاً عن ذلك لم يحظ المعادل الموضوعي بدراسة مستوفية فاحصة وبقراءة واضحة تلامس المعرفة والإحساس. يُعدّ ديوان ((أسير الموج)) ذا رمزية ثقافية عالية في دولة الامارات العربية المتحدة، لأنه يحاكي ظواهر اجتماعية متعددة أخذت على عاتقها تحفيز الوعي الوطني والإحساس بالمسؤولية وإثبات الهوية ؛ متواشجة بالالتزام النفسي والأخلاقي تجاه الوطن، ورفع اسمه ورايته خفاقة أبداً ودائماً. فكان من دواعي البحث قراءة المعادل الموضوعي على وفق ما أراد مبتكره ؛ لما أصابه من غموض وعدم إهتمام من الدارسين، وعدم ذكرهم إياه إلا ضمناً في كتبهم أو دراساتهم ؛ فضلاً عن ذلك دراسة ديوان ((أسير الموج)) للشاعر ((نايف عبد الله الهريس)) ؛ وبيان مواطن الضعف والقوة الشعرية في الديوان، ومدى صلة شعرية الشاعر بالمعادل الموضوعي. تُعد المناهج البحثية أداة مثلى للوصول إلى نتائج مرضية، وإلى الوقوف على الحقائق التي أدت لتعدد المفاهيم والتسميات للمعادل الموضوعي، لذا كان المنهج الثقافي النقدي الحديث خير عون للوصول إلى تلك النتائج. ولأهمية المعادل في تعليل الظواهر الحسية والمعقدة الكثيرة في الأدب العربي، ومتابعتها عن كثب، وجب قراءتها بصورة واضحة كي يتجلى المكنون في رؤية المعادل الموضوعي. جاء البحث ليضم بين طياته، موضوعات عدة كان أهمها، المعادل الموضوعي (الأصول والتجليات)، بعدها عرج على الشعر العربي الحديث ومتغيراته، ثم التعريف بالشاعر نايف الهريس ووصف ديوان أسير الموج، وبعدها كان انتقاء قصائد من الديوان لغرض التطبيق النقدي عليها، بوصفها معادلاً موضوعياً، وخرج البحث بخاتمة تُبَين رؤاه، مذيلةً بقائمة لمصادره ومراجعه. والله ولي التوفيق

Objectives: Many barriers contribute to the underutilization of hydroxyurea (HU) in the treatment of sickle cell disease (SCD), and adherence to its use is often reported to be suboptimal. It is important to have information on the safety of HU in patients with SCD. Our study assessed the pattern of use, patients’ adherence to medication, discontinuation of use, and safety of HU in patients with SCD. Methods: This cross-sectional study was conducted in the department of medicine of a referral hospital in Oman over five months and included a review of patient files and patient interview. Approval was obtained from the Regional Research and Ethics Committee of the A'Dakhiliyah Governorate and the hospital administration. The parameters were compared between groups using the chi-square test. Results: Of 298 patients studied, 128 (43.0%) had used HU at some points. The difference in the prevalence of HU use was statistically significant based only on age (p = 0.014), with younger patients more likely to be currently using HU or used HU in the past. The majority of patients were adherent (82.5%) based on self-reported adherence. The prevalence of discontinuation (temporary or permanent) of HU use was high (57.0%), and suspected adverse drug reaction (ADR) was the most common reason. Among those who had never used HU, 33.7% of patients had an indication for the initiation of HU. A quarter of patients who used HU developed a suspected ADR, with blood abnormalities being the commonest. The duration of HU use influenced ADR prevalence (p = 0.015). Conclusions: Among the current users of HU, the majority of the patients were adherent based on self-reported medication adherence. The prevalence of discontinuation of HU use and instances of non-initiation of HU among those indicated were high. A larger study, ideally of a prospective nature, in various governorates of Oman, would provide a wider picture at the national level.

This study investigated the effects corn oil (CO) and different ratios of corn oil plus fish oil (FO) on insulin signaling in rat's heart. Adult male rats were fed low (LFD) or isocaloric high-fat diets (HFDs) of CO alone or CO + FO (ratios of 9:1 or 4:1). Cultured cardiomyocytes were treated with linoleic acid (LA), DHA + EPA (1:1) or LA + (DHA + EPA) (1:1). CO induced peripheral and cardiac insulin resistance with mitochondria damage, lipotoxicity activation of PKCε. It also upregulated LV levels of PPARα and down regulated PPARβ/δ. FO antagonized corn oil effects at both ratio with more profound effects with the ratio of 4:1. The regulatory roles of CO and FO on PPARs was shown in cultured cardiomyocytes and independent of hyperinsulinemia or free fatty acids. In conclusion, reducing the ratio of n-6/n-3 PUFAs in our diet toward a value of one is cardioprotective.

Abstract Hemoglobin La Desirade (Hb La Desirade) is an unstable hemoglobin variant characterized by amino acid Alanine (Ala) replacing Valine (Val) at position 129 (H7) in the beta chain. Hb La Desirade exhibits a decreased oxygen affinity and normal heme-heme interaction. Interestingly, on analysis by standard electrophoresis, it migrates in the same region as normal HbA, and HbA actually represents a combination of HbA and Hb La Desirade together. This variant was reported as compound heterozygous with other Hemoglobin variants such as HbS, HbC or beta thalassemia, and more recently with Southeast Asian ovalocytosis and Hb Louisville with varying clinical manifestations. Herein, we describe the clinical and laboratory findings in a number of Omani Arab families who presented to our service for various reasons, presenting with Hemoglobin La Desirade with sickle gene and alpha thalassemia. Our patients with Hb La Desirade trait, were clinically asymptomatic with no evidence of anemia. However when it is associated with other abnormal hemoglobin variants such as HbS, leading to sickle/La Desirade compound heterozygosity, there was mild anemia with significant degree of hypochromia and microcytosis. The most striking feature was that the levels of HbS and HbA were almost equal on HPLC, and these cases could be misdiagnosed as sickle cell trait (SCT). However, the levels of Hb S in these compound heterozygotes (40.4-45.9) were higher than normally seen for the diagnosis of SCT in this population.

Introduction This pilot study evaluated the impact of a diabetes-specific nutritional shake (DSNS) used twice daily by people with type 2 diabetes (T2D) on glycemic response assessed by continuous glucose monitoring (CGM).Research design and methods Adults (n=81) with T2D managed by oral medications were studied in a randomized, open-label, three-group parallel study design. The study was conducted in two phases over 14 days: Baseline (days 1–6), during which study participants consumed their habitual self-selected diets (SSD), followed by the Intervention (days 7–14), during which participants were randomized as follows: (1) SSD group received no study product (n=32); (2) DSNS breakfast/afternoon snack (Bkfst/AS) group consumed one DSNS as a breakfast meal replacement and a second to replace their mid-afternoon snack (n=24); (3) DSNS breakfast/prebed snack (Bkfst/PBS) group consumed one DSNS as a breakfast meal replacement and added a second as a prebed snack (n=25). Glucose was assessed by CGM throughout the study. Additionally, participants were asked about snacking behaviors, cravings, and other questions related to the use of DSNS as meal replacements and snacks.Results All groups reduced their postprandial glycemic response (positive area under the curve (pAUC, mg/min*dL−1)) and adjusted peak value (mg/dL) when compared with the baseline phase. Participants consuming DSNS in place of their usual breakfast showed greater reductions in pAUC compared with the SSD group (p=0.008) for the DSNS Bkfst/AS group with a trend (p=0.069) for the DSNS Bkfst/PBS group. Adjusted peak value showed greater reductions in both DSNS groups as compared with the SSD group (p=0.002 for DSNS Bkfst/AS and p=0.010 for DSNS Bkfst/PBS). Nocturnal glucose variability was significantly decreased during the intervention phase compared with baseline phase in the DSNS Bkfst/AS group (p=0.020), with no significant differences between groups. After intervention, the DSNS Bkfst/AS group had a significantly lower percentage of participants (17%) reporting cravings for starchy meals/sides compared with before the study (33%) (p=0.046). This group also reported a significant increase in confidence in choosing foods to control their diabetes (from 58.3% to 91.7%, preintervention vs postintervention, respectively, p=0.005).Conclusions Use of DSNS to replace breakfast and as an afternoon snack improves both glycemic control and behavioral factors related to dietary management of diabetes.Trail registration number NCT04230889.

Insecticides and toxicants abound in nature, posing a health risk to humans. Concurrent exposure to many environmental contaminants has been demonstrated to harm myocardial performance and reduce cardiac oxidative stress. The purpose of this research was to study the protective effect of vitamin C (Vit C) on quinalphos (QP)-induced cardiac tissue damage in rats. Eighteen albino male rats were randomly categorised into three groups (n = 6). Control, QP group: rats received distilled water. QP insecticide treatment: an oral administration of QP incorporated in drinking water. QP + Vit C group: rats received QP and Vit C. All the experiments were conducted for ten days. Decline of cardiac antioxidant biomarkers catalase (CAT) and reduced glutathione (GPx) along with increased proinflammatory markers tumour necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6) indicated oxidative and inflammatory damage to the heart following administration of QP when compared to control rats. The light microscopic and ultrastructure appearance of QP-treated cardiomyocytes exhibited cardiac damage. Administration of Vit C showed decreased oxidative and inflammatory biomarkers, confirmed with histological and electron microscopic examination. In conclusion, Vit C protected the heart from QP-induced cardiac damage due to decreased inflammation and oxidative stress.

Malignant pleural mesothelioma (MPM) is a malignant tumor of the mesothelial lining of the thorax. It has been related to frequent exposure to asbestos. Diagnosis of malignant pleural mesothelioma is considered a criticizing problem for clinicians. Early diagnosis and sufficient surgical excision of MPM are considered the cornerstone success factors for the management of early MPM. Glutathione peroxidase-1 (GPX1) is an intracellular protein found to be extensively distributed in all cells, and it belongs to the GPX group. In the current study, we included ninety-eight patients with MPM that underwent surgery at the Zagazig University Hospital in Egypt. We assessed GPX1 gene expression level as it was thought to be related to pathogenicity of cancer in a variety of malignant tumors. We observed a significant elevation in GPX1-mRNA levels in MPM relative to the nearby normal pleural tissues. It was found to be of important diagnostic specificity in the differentiation of MPM from normal tissues. Moreover, we studied the survival of patients in correlation to the GPX1 expression levels and we reported that median overall survival was about 16 months in patients with high GPX1 expression levels, while it was found to be about 40 months in low GPX1 levels.

Nipah virus is one of the most harmful emerging viruses with deadly effects on both humans and animals. Because of the severe outbreaks, in 2018, the World Health Organization focused on the urgent need for the development of effective solutions against the virus. However, up to date, there is no effective vaccine against the Nipah virus in the market. In the current study, the complete proteome of the Nipah virus (nine proteins) was analyzed for the antigenicity score and the virulence role of each protein, where we came up with fusion glycoprotein (F), glycoprotein (G), protein (V), and protein (W) as the candidates for epitope prediction. Following that, the multitope vaccine was designed based on top-ranking CTL, HTL, and BCL epitopes from the selected proteins. We used suitable linkers, adjuvant, and PADRE peptides to finalize the constructed vaccine, which was analyzed for its physicochemical features, antigenicity, toxicity, allergenicity, and solubility. The designed vaccine passed these assessments through computational analysis and, as a final step, we ran a docking analysis between the designed vaccine and TLR-3 and validated the docked complex through molecular dynamics simulation, which estimated a strong binding and supported the nomination of the designed vaccine as a putative solution for Nipah virus. Here, we describe the computational approach for design and analysis of this vaccine.

Moraxella catarrhalis (M. catarrhalis) is a Gram-negative bacterium that can cause serious respiratory tract infections and middle ear infections in children and adults. M. catarrhalis has demonstrated an increasing rate of antibiotic resistance in the last few years, thus development of an effective vaccine is a major health priority. We report here a novel designed multitope vaccine based on the mapped epitopes of the vaccine candidates filtered out of the whole proteome of M. catarrhalis. After analysis of 1615 proteins using a reverse vaccinology approach, only two proteins (outer membrane protein assembly factor BamA and LPS assembly protein LptD) were nominated as potential vaccine candidates. These proteins were found to be essential, outer membrane, virulent and non-human homologs with appropriate molecular weight and high antigenicity score. For each protein, cytotoxic T lymphocyte (CTL), helper T lymphocyte (HTL) and B cell lymphocyte (BCL) epitopes were predicted and confirmed to be highly antigenic and cover conserved regions of the proteins. The mapped epitopes constituted the base of the designed multitope vaccine where suitable linkers were added to conjugate them. Additionally, beta defensin adjuvant and pan-HLA DR-binding epitope (PADRE) peptide were also incorporated into the construct to improve the stimulated immune response. The constructed multitope vaccine was analyzed for its physicochemical, structural and immunological characteristics and it was found to be antigenic, soluble, stable, non-allergenic and have a high affinity to its target receptor. Although the in silico analysis of the current study revealed that the designed multitope vaccine has the ability to trigger a specific immune response against M. catarrhalis, additional translational research is required to confirm the effectiveness of the designed vaccine.