First microscopic, pathological, epidemiological, and molecular investigation of Leucocytozoon (Apicomplexa: Haemosporida) parasites in Egyptian pigeons.

Introduction: Leucocytozoon is an intracellular blood parasite that affects various bird species globally and is transmitted by blackfly vectors. This parasite is responsible for leucocytozoonosis, a disease that results in significant economic losses due to reduced meat and egg production. There is limited knowledge about the epidemiological pattern of leucocytozoonosis and its causative species in Egypt, particularly in pigeons. Methods: The current study involved the collection of 203 blood samples from domestic pigeons from various household breeders and local markets across Qena Province, Upper Egypt. Samples were initially examined for potential Leucocytozoon infection using blood smears, followed by an evaluation of associated risk factors. Molecular identification of the parasite in selected samples (n = 11), which had initially tested positive via blood smears, was further refined through nested PCR and sequence analysis of the mitochondrial cytochrome b gene to ascertain the Leucocytozoon species present. Additionally, histopathological examination of the liver, spleen, and pancreas was conducted on animals that tested positive by blood smears. Results: Interestingly, 26 out of 203 samples (12.08%) had confirmed Leucocytozoon infections based on microscopic analysis. Additionally, all 11 samples that initially tested positive via blood smears were confirmed positive through nested PCR analysis, and their sequencing revealed the presence of Leucocytozoon sabrazesi, marking the first report of this parasite in Egypt. The study into potential risk factors unveiled the prevalence of Leucocytozoon spp. seems host gender-dependent, with males exhibiting a significantly higher infection rate (33.33%). Additionally, adult birds demonstrated a significantly higher infection prevalence than squabs, suggesting an age-dependent trend in prevalence. Seasonality played a significant role, with the highest occurrence observed during summer (37.25%). Histopathological examination revealed the presence of numerous megaloschizonts accompanied by lymphocytic infiltration and multiple focal areas of ischemic necrosis. Conclusion: To our knowledge, this is the first study to shed light on the epidemiological characteristics and molecular characterization of leucocytozoonosis in pigeons in Egypt. Further research endeavors are warranted to curb the resurgence of Leucocytozoon parasites in other avian species across Egypt, thereby refining the epidemiological understanding of the disease for more effective control and prevention measures.

Antibiotic resistance and its correlation with biofilm formation and virulence genes in Klebsiella pneumoniae isolated from wounds.

Klebsiella pneumoniae is the most important species of the Klebsiella genus and often causes hospital infections. These bacteria have a high resistance to most of the available drugs, which has caused concern all over the world. In this study, we investigated the antibiotic resistance profile and the ability to produce extended-spectrum beta-lactamase (ESBL) among K. pneumoniae isolates, and then we investigated the relationship between these two factors with biofilm formation and the prevalence of different virulence genes. In this study, 130 isolates of K. pneumoniae isolated from wounds were investigated. The antibiotic resistance of the isolates was evaluated by the disk diffusion method. The microtiter plate method was used to measure biofilm formation. The prevalence of virulence genes was detected by multiplex PCR. Among the examined isolates, 85.3% showed multidrug resistance. 87.6% of the isolates were ESBL-positive. Imipenem, meropenem, and fosfomycin were the most effective drugs. The ability of the isolates to produce biofilm was strong (80%), moderate (12.3%), and weak (7.6%), respectively. fimH, mrKD, entB, and tolC virulence genes were observed in all isolates. High prevalence of antibiotic resistance (especially multidrug resistance), high prevalence of ESBL-producing isolates, the ability of all isolates to biofilm formation, and the presence of fimH, mrKD, entB, and tolC virulence genes in all isolates show the importance of these factors in the pathogenesis of K. pneumoniae isolates in Iraq.

Biomedical Promise of Aspergillus Flavus-Biosynthesized Selenium Nanoparticles: A Green Synthesis Approach to Antiviral, Anticancer, Anti-Biofilm, and Antibacterial Applications.

This study utilized Aspergillus flavus to produce selenium nanoparticles (Se-NPs) in an environmentally friendly and ecologically sustainable manner, targeting several medicinal applications. These biosynthesized Se-NPs were meticulously characterized using X-ray diffraction (XRD), Fourier-transform infrared (FT-IR) spectroscopy, transmission electron microscope (TEM), and UV-visible spectroscopy (UV), revealing their spherical shape and size ranging between 28 and 78 nm. We conducted further testing of Se-NPs to evaluate their potential for biological applications, including antiviral, anticancer, antibacterial, antioxidant, and antibiofilm activities. The results indicate that biosynthesized Se-NPs could be effective against various pathogens, including Salmonella typhimurium (ATCC 14028), Bacillus pumilus (ATCC 14884), Staphylococcus aureus (ATCC 6538), Clostridium sporogenes (ATCC 19404), Escherichia coli (ATCC 8739), and Bacillus subtilis (ATCC 6633). Additionally, the biosynthesized Se-NPs exhibited anticancer activity against three cell lines: pancreatic carcinoma (PANC1), cervical cancer (Hela), and colorectal adenocarcinoma (Caco-2), with IC50 values of 177, 208, and 216 µg/mL, respectively. The nanoparticles demonstrated antiviral activity against HSV-1 and HAV, achieving inhibition rates of 66.4% and 15.1%, respectively, at the maximum non-toxic concentration, while also displaying antibiofilm and antioxidant properties. In conclusion, the biosynthesized Se-NPs by A. flavus present a promising avenue for various biomedical applications with safe usage.

Detection of novel PPP1R1B::STARD3 fusion transcript in acute myeloid leukemia: a case report.

BACKGROUND: Acute myeloid leukemia (AML) is the second most common type of leukemia in children. Although prognostic and diagnostic tests of AML patients have improved, there is still a great demand for new reliable clinical biomarkers for AML. Read-through fusion transcripts (RTFTs) are complex transcripts of adjacent genes whose molecular mechanisms are poorly understood. This is the first report of the presence of the PPP1R1B::STARD3 fusion transcript in an AML patient. Here, we investigated the presence of PPP1R1B::STARD3 RTFT in a case of AML using paired-end RNA sequencing (RNA-seq). CASE PRESENTATION: A Persian 12-year-old male was admitted to Dr. Sheikh Hospital of Mashhad, Iran, in September 2019 with the following symptoms, including fever, convulsions, hemorrhage, and bone pain. The patient was diagnosed with AML (non-M3-FAB subtype) based on cell morphologies and immunophenotypical features. Chromosomal analysis using the G-banding technique revealed t (9;22) (q34;q13). CONCLUSIONS: Single-cell RNA sequencing (scRNA-seq) analysis suggested that the PPP1R1B promoter may be responsible for the PPP1R1B::STARD3 expression. Alterations in the level of lipid metabolites implicate cancer development, and this fusion can play a crucial role in the cholesterol movement in cancer cells. PPP1R1B::STARD3 may be considered a candidate for targeted therapies of the cholesterol metabolic and the PI3K/AKT signaling pathways involved in cancer development and progression.

Novel gene-specific Bayesian Gaussian mixture model to predict the missense variants pathogenicity of Sanfilippo syndrome.

MPS III is an autosomal recessive lysosomal storage disease caused mainly by missense variants in the NAGLU, GNS, HGSNAT, and SGSH genes. The pathogenicity interpretation of missense variants is still challenging. We aimed to develop unsupervised clustering-based pathogenicity predictor scores using extracted features from eight in silico predictors to predict the impact of novel missense variants of Sanfilippo syndrome. The model was trained on a dataset consisting of 415 uncertain significant (VUS) missense NAGLU variants. Performance The SanfilippoPred tool was evaluated by validation and test datasets consisting of 197-labelled NAGLU missense variants, and its performance was compared versus individual pathogenicity predictors using receiver operating characteristic (ROC) analysis. Moreover, we tested the SanfilippoPred tool using extra-labelled 427 missense variants to assess its specificity and sensitivity threshold. Application of the trained machine learning (ML) model on the test dataset of labelled NAGLU missense variants showed that SanfilippoPred has an accuracy of 0.93 (0.86-0.97 at CI 95%), sensitivity of 0.93, and specificity of 0.92. The comparative performance of the SanfilippoPred showed better performance (AUC = 0.908) than the individual predictors SIFT (AUC = 0.756), Polyphen-2 (AUC = 0.788), CADD (AUC = 0.568), REVEL (AUC = 0.548), MetaLR (AUC = 0.751), and AlphMissense (AUC = 0.885). Using high-confidence labelled NAGLU variants, showed that SanfilippoPred has an 85.7% sensitivity threshold. The poor correlation between the Sanfilippo syndrome phenotype and genotype represents a demand for a new tool to classify its missense variants. This study provides a significant tool for preventing the misinterpretation of missense variants of the Sanfilippo syndrome-relevant genes. Finally, it seems that ML-based pathogenicity predictors and Sanfilippo syndrome-specific prediction tools could be feasible and efficient pathogenicity predictors in the future.

Discovery of new 2-(3-(naphthalen-2-yl)-4,5-dihydro-1H-pyrazol-1-yl)thiazole derivatives with potential analgesic and anti-inflammatory activities: In vitro, in vivo and in silico investigations.

Joining the global demand for the discovery of potent NSAIDs with minimized ulcerogenic effect, new pyrazole clubbed thiazole derivatives 5a-o were designed and synthesized. The new derivatives were initially evaluated for their analgesic activity. Eight compounds 5a, 5c, 5d, 5e, 5f, 5h, 5m, and 5o showed higher activity than Indomethacin (potency = 105-130 % vs. 100 %). Subsequently, they were picked for further evaluation of their anti-inflammatory activity, ulcerogenic liability as well as toxicological studies. Derivatives 5h and 5m showed a potential % edema inhibition after 3 h (79.39 % and 72.12 %, respectively), with a promising safety profile and low ulcer indices (3.80 and 3.20, respectively). The two compounds 5h and 5m were subjected to in vitro COX-1 and COX-2 inhibition assay. The candidate 5h showed nearly equipotent COX-1 inhibition (IC50 = 38.76 nM) compared to the non-selective reference drug Indomethacin (IC50 = 35.72 nM). Compound 5m expressed significant inhibitory activities and a higher COX-2 selectivity index (IC50 = 87.74 nM, SI = 2.05) in comparison with Indomethacin (SI = 0.52), with less selectivity than Celecoxib (SI = 8.31). Simulation docking studies were carried out to gain insights into the binding interaction of compounds 5h and 5m in the vicinity of COX-1 and COX-2 enzymes that illustrated the importance of pyrazole clubbed thiazole core in hydrogen bonding interactions. The thiazole motif of compounds 5h and 5m exhibited a well orientation toward COX-1 Arg120 key residue by hydrogen bonding interactions. Compound 5h revealed an additional arene-cation interaction with Arg120 that could rationalize its superior COX-1 inhibitory activity. Compounds 5h and 5m overlaid the co-crystallized ligand Celecoxib I differently in the active site of COX-2. Compound 5m showed an enhanced accommodation with binding energy of - 6.13 vs. - 1.70 kcal/mol of compounds 5h. The naphthalene ring of compound 5m adopted the Celecoxib I benzene sulfonamide region that is stabilized by hydrogen-arene interactions with the hydrophobic sidechains of the key residues Ser339 and Phe504. Further, the core structure of compound 5m, pyrazole clubbed thiazole, revealed deeper hydrophobic interactions with Ala513, Leu517 and Val509 residues. Finally, a sensitive and accurate UPLC-MS/MS method was developed for the simultaneous estimation of some selected promising pyrazole derivatives in rat plasma. Accordingly, compounds 5h and 5m were suggested to be promising potent analgesic and anti-inflammatory agents with improved safety profiles and a novel COX isozyme modulation activity.

Design, synthesis, and biological evaluation of dinaciclib and CAN508 hybrids as CDK inhibitors.

The scaffolds of two known CDK inhibitors (CAN508 and dinaciclib) were the starting point for synthesizing two series of pyarazolo[1,5-a]pyrimidines to obtain potent inhibitors with proper selectivity. The study presented four promising compounds; 10d, 10e, 16a, and 16c based on cytotoxic studies. Compound 16a revealed superior activity in the preliminary anticancer screening with GI % = 79.02-99.13 against 15 cancer cell lines at 10 µM from NCI full panel 60 cancer cell lines and was then selected for further investigation. Furthermore, the four compounds revealed good safety profile toward the normal cell lines WI-38. These four compounds were subjected to CDK inhibitory activity against four different isoforms. All of them showed potent inhibition against CDK5/P25 and CDK9/CYCLINT. Compound 10d revealed the best activity against CDK5/P25 (IC50 = 0.063 µM) with proper selectivity index against CDK1 and CDK2. Compound 16c exhibited the highest inhibitory activity against CDK9/CYCLINT (IC50 = 0.074 µM) with good selectivity index against other isoforms. Finally, docking simulations were performed for compounds 10e and 16c accompanied by molecular dynamic simulations to understand their behavior in the active site of the two CDKs with respect to both CAN508 and dinaciclib.

First molecular identification and phylogenetic illustration of Sarcocystis species infection in Red Sea shortfin mako shark (Isurus oxyrinchus Rafinesque, 1810).

BACKGROUND: members of the genus Sarcocystis are intracellular obligate protozoan parasites classified within the phylum Apicomplexa and have an obligate heteroxenous life cycle involving two hosts. A more comprehensive understanding of the prevalence and geographic range of different Sarcocystis species in marine ecosystems is needed globally and nationally. Hence, the objective of this study was to document the incidence of Sarcocystis infection in sharks within the aquarium ecosystem of Egypt and to identify the species through the characterization of the SSU rDNA gene. METHODS: All organs of the mako shark specimen underwent macroscopic screening to detect the existence of a Sarcocystis cyst. Ten cysts were collected from the intestine and processed separately to extract the genomic DNA. The polymerase chain reaction (PCR) was accomplished by amplifying a specific 18S ribosomal RNA (rRNA) gene fragment. Subsequently, the resulting amplicons were subjected to purification and sequencing processes. RESULTS: Macroscopic examination of the mako shark intestinal wall sample revealed the presence of Sarcocystis cysts of various sizes and shapes, and sequencing of the amplicons from Sarcocystis DNA revealed a 100% nucleotide identity with the sequence of Sarcocystis tenella recorded from sheep in Iran; The mako shark sequence has been deposited in the GeneBank with the accession number OQ721979. This study presents the first scientific evidence demonstrating the presence of the Sarcocystis parasite in sharks, thereby documenting this specific marine species as a novel intermediate host in the Sarcocystis life cycle. CONCLUSIONS: This is the first identification of Sarcocystis infection in sharks, and we anticipate it will be an essential study for future screenings and establishing effective management measures for this disease in aquatic ecosystems.

Exploring new quinazolin-4(3H)-one derivatives as CDK2 inhibitors: Design, synthesis, and anticancer evaluation.

In the present work, five series of new 2,3-disubstituted quinazolin-4(3H)-ones 4a-c, 5a-d, 6a-g, 7a,b, and 9a-c were designed, synthesized, and screened in vitro for their cytotoxic activity against 60 cancer cell lines by the National Cancer Institute, USA. Five candidates 4c, 6a, 6b, 6d, and 6g revealed promising cytotoxicity with significant percentage growth inhibition in the range of 81.98%-96.45% against the central nervous system (CNS) (SNB-19), melanoma (MDA-MB-435), and non-small cell lung cancer (HOP-62) cell lines. The in vitro cytotoxic half maximal inhibitory concentration (IC50 ) values for the most active compounds 4c, 6a, 6b, 6d, and 6g against the most sensitive cell lines were evaluated. Additionally, screening their cyclin-dependent kinase 2 (CDK2) inhibitory activity was performed. Ortho-chloro-benzylideneamino derivative 6b emerged as the most potent compound with IC50 = 0.67 µM compared to Roscovitine (IC50 = 0.64 µM). The most active candidates arrested the cell cycle at G1, S phases, or both, leading to cell death and inducing apoptosis against CNS (SNB-19), melanoma (MDA-MB-435), and non-small cell lung cancer (HOP-62) cell lines. The molecular docking study verified the resulting outcomes for the most active candidates in the CDK2-binding pocket. Finally, physicochemical, and pharmacokinetic properties deduced that compounds 4c, 6a, 6b, 6d, and 6g displayed significant drug-likeness properties. According to the obtained results, the newly targeted compounds are regarded as promising scaffolds for the continued development of novel CDK2 inhibitors.

Association of IL-10-592 C > A /-1082 A > G and the TNFα -308 G > A with susceptibility to COVID-19 and clinical outcomes.

BACKGROUND: Variation in host immune responses to SARS-CoV-2 is regulated by multiple genes involved in innate viral response and cytokine storm emergence like IL-10 and TNFa gene polymorphisms. We hypothesize that IL-10; -592 C > A and - 1082 A > G and TNFa-308 G > A are associated with the risk of SARS-COV2 infections and clinical outcome. METHODS: Genotyping, laboratory and radiological investigations were done to 110 COVID-19 patients and 110 healthy subjects, in Ismailia, Egypt. RESULTS: A significant association between the - 592 A allele, A containing genotypes under all models (p < 0.0001), and TNFa A allele with risk to infection was observed but not with the G allele of the - 1082. The - 592 /-1082 CG and the - 592 /-1082/ -308 CGG haplotypes showed higher odds in COVID-19 patients. Severe lung affection was negatively associated with - 592, while positive association was observed with - 1082. Higher D-dimer levels were strongly associated with the - 1082 GG genotype. Survival outcomes were strongly associated with the GA genotype of TNFa. -308 as well as AGG and AAA haplotypes. CONCLUSION: IL-10 and TNFa polymorphisms should be considered for clinical and epidemiological evaluation of COVID-19 patients.

Metabolomic profiling and quantification of polyphenols from leaves of seven Acacia species by UHPLC-QTOF-ESI-MS.

The genus Acacia (Fabaceae) comprises >1350 species and has been used in traditional medicine as infusions and decoctions to treat wounds, sores, headaches, diarrhea, and cough. The leaf methanolic extracts of seven Acacia species growing in Egypt namely: Acacia saligna, Acacia seyal, Acacia xanthophloea, Acacia tortilis subsp. raddiana., Acacia tortilis, Acacia laeta, Acacia albida were analyzed using UPLC-QTOF-ESI-MS. A total of 37 polyphenols were identified and discussed in detail. They included phenolic acids, flavonoids, and procyanidins, among which sixteen polyphenols were identified in Acacia for the first time. Folin-ciocalteau assay and ferric reducing antioxidant power, cupric reducing antioxidant capacity, 2,20 -azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) cation radical and the scavenging capacity against 2,2-diphenyl-1- picrylhydrazyl radical were performed to investigate the total phenolic content and the antioxidant activity of the Acacia extracts, respectively. Furthermore, the absolute quantification of eighteen polyphenols common to most of the species was performed using UPLC-MS. It was evident that the differences in the chemical composition among the species accounted for the difference in antioxidant activity which was in line together with the total phenolic content.

Prevalence and first molecular identification of Sarcocystis species in feces of domestic dogs (Canis familiaris) in Egypt.

BACKGROUND: Sarcocystis species are obligatorily heteroxenous protozoan parasites with predator-prey life cycles. Global Knowledge about the epidemiology and the distribution pattern of different Sarcocystis species in dog feces are very scarce. Therefore, the current investigation was conducted to declare the occurrence of Sarcocystis in the fecal specimens of the most common canids in Egypt, the domestic dogs, and to identify the species present using various parasitological and molecular approaches. METHODS: A total of 100 dog fecal samples were collected and screened using fecal sugar flotation test for the presence of Sarcocystis oocysts/sporocysts. Additionally, thirty samples were used for genomic DNA extraction. The 18S rRNA gene fragment was the target of primers for a PCR, followed by purification and sequencing of the amplicons. RESULTS: Currently, the results obtained reviewed that 4% of fecal samples were positive for Sarcocystis spp. using LM. Additionally, Sarcocystis spp. were verified in sixteen dogs (53.3%, 16/30) using PCR and subsequent sequencing protocols. Statistically, insignificant difference in prevalence of sarcocystosis relative to age and gender was noticed. Morphologically, the detected sporocysts measured 13.2-16.0 × 9.4-11 µm. Based on the 18S rRNA gene, sequencing analysis of amplicons from sporocysts DNA revealed 99.82% nucleotide homology with published S. tenella partial nucleotide sequences from sheep in Iraq and Iran. CONCLUSIONS: This is the first molecular evidence in support of the final host role of domestic dogs in the life cycle of S. tenella in Egypt, which provides a precious diagnostic tool for further epidemiological studies and for the assessment of the effectiveness of control measures for this disease.

Structural Analysis and Activity Correlation of Amphiphilic Cyclic Antimicrobial Peptides Derived from the [W4R4] Scaffold.

In our ongoing quest to design effective antimicrobial peptides (AMPs), this study aimed to elucidate the mechanisms governing cyclic amphiphilic AMPs and their interactions with membranes. The objective was to discern the nature of these interactions and understand how peptide sequence and structure influence antimicrobial activity. We introduced modifications into the established cyclic AMP peptide, [W4R4], incorporating an extra aromatic hydrophobic residue (W), a positively charged residue (R), or the unique 2,5-diketopiperazine (DKP). This study systematically explored the structure-activity relationships (SARs) of a series of cyclic peptides derived from the [W4R4] scaffold, including the first synthesis and evaluation of [W4R4(DKP)]. Structural, dynamic, hydrophobic, and membrane-binding properties of four cyclic peptides ([W4R4], [W5R4], [W4R5], [W4R4(DKP)]) were explored using molecular dynamics simulations within a DOPC/DOPG lipid bilayer that mimics the bacterial membrane. The results revealed distinct SARs linking antimicrobial activity to parameters such as conformational plasticity, immersion depth in the bilayer, and population of the membrane binding mode. Notably, [W4R5] exhibited an optimal "activity/binding to the bacterial membrane" pattern. This multidisciplinary approach efficiently decoded finely regulated SAR profiles, laying a foundation for the rational design of novel antimicrobial peptides.

Circulating ESR1, long non-coding RNA HOTAIR and microRNA-130a gene expression as biomarkers for breast cancer stage and metastasis.

Breast cancer, the most prevalent cancer among women, has posed a significant challenge in identifying biomarkers for early diagnosis and prognosis. This study aimed to elucidate the gene expression profile of Estrogen Receptor-1 (ESR-1), long non-coding RNA HOTAIR, and microRNA-130a in the serum of Egyptian breast cancer patients, evaluating the potential of HOTAIR and miR-130a as biomarkers for predicting pathological parameters in BC. The study involved 45 patients with primary BC, with serum samples collected preoperatively and postoperatively twice. The expression levels of ESR-1, HOTAIR, and miR-130a were quantified using real-time PCR and analyzed for correlations with each other and with the clinical and pathological parameters of the patients. Serum HOTAIR levels exhibited a strong positive association with metastasis and demonstrated a significant increase after 6 months in all patients with locally advanced and stage IV BC. Conversely, tumors with advanced stages and metastatic lesions showed significantly lower expression levels of miR-130a. Notably, a significant positive correlation was observed between preoperative ESR-1 expression and both HOTAIR and miR-130a levels. Serum HOTAIR and miR-130a levels have emerged as promising non-invasive biomarkers with the potential to predict the pathological features of BC patients. HOTAIR, an oncogenic long non-coding RNA (lncRNA), and miR-130a, a tumor suppressor miRNA, play crucial roles in tumor progression. Further investigations are warranted to elucidate the intricate interplay between HOTAIR and miR-130a and to fully comprehend the contribution of HOTAIR to BC recurrence and its potential utility in early relapse prediction.

Anticonvulsant Classes and Possible Mechanism of Actions.

Epilepsy is considered one of the most common neurological disorders worldwide; it needs long-term or life-long treatment. Despite the presence of several novel antiepileptic drugs, approximately 30% patients still suffer from drug-resistant epilepsy. Subsequently, searching for new anticonvulsants with lower toxicity and better efficacy is still in paramount demand. Using target-based studies in the discovery of novel antiepileptics is uncommon owing to the insufficient information on the molecular pathway of epilepsy and complex mode of action for most of known antiepileptic drugs. In this review, we investigated the properties of anticonvulsants, types of epileptic seizures, and mechanism of action for anticonvulsants.

Prevalence and risk factors associated with Toxocara canis in dogs and humans in Egypt: A comparative approach.

BACKGROUND: Dogs are the most popular pet animals worldwide, and their frequent and close contact with humans poses an increased risk of zoonotic parasite transmission. Toxocara canis infection is a highly pervasive and economically significant zoonotic infection transmitted by dogs worldwide, commonly in tropical and subtropical regions, particularly in developing countries. OBJECTIVES: This study evaluates the epidemiological profile and associated risk factors of T. canis exposure among humans and T. canis infection in domestic dogs in two climatically different governorates in Egypt. METHODS: Faecal samples from 360 domiciled dogs were examined using the flotation technique to detect T. canis eggs. In addition, 276 human serum samples were evaluated by enzyme-linked immunosorbent assay over a period of 10 months from May 2021 to February 2022 in the Alexandria and Qena Governorates, Egypt. RESULTS: Shedding of T. canis was identified in 33.33% (120/360) of dogs and the overall seroprevalence in the human population was 20.65% (57/276). Lower Egypt, represented by the Alexandria Governorate, had higher canine infection (39.47%) and human seropositivity (29.87%) rates than those of Upper Egypt, represented by Qena Governorate (26.47% and 9.02% in dogs and humans, respectively). Statistical analysis of the sociodemographic characteristics of the participants revealed that handwashing, washing of vegetables and fruits and sex were associated with human T. canis exposure. CONCLUSION: The prevalence rates of confirmed T. canis infection in the Egyptian dogs population and the associated human seropositivity rates reflect its importance as a public health concern and support the call to increase public awareness of this issue. The risk factors identified in this study can contribute to the development of more effective control and prevention strategies.

Comparison between levels of Homocysteine, Interleukin-6 and Interleukin-10 in severe cases of Egyptian COVID-19 patients.

Coronavirus disease 2019 (COVID-19) is the reason of an outbreak of respiratory illnesses ranging from typical cold to severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome. We intended to compare levels of IL-6, IL-10, and homocysteine in the sera of severe COVID-19 Egyptian patients and connect them with the extent of the illness. This cross-sectional study included 90 COVID-19 Egyptian patients. They included 45 non severe cases (group 1) and 45 severe cases (group 2). There was statistically significantly increase in IL-6 in group 2 (median = 7.05, IQR = 6.2 - 7.9; p < 0.001) in comparison to group 1 (median = 4.96, IQR = 4.5 - 5.8) and statistically significantly increase in IL-10 in group 2 (154.1 ± 73.3) in comparison to group 1 (47.04 ± 23.8; p < 0.001). There were no variations in the examined groups' homocysteine levels (p= 0.318). Furthermore, there was statistically substantial positive connection (r=0.30) between IL-6 and AST (p=0.046) and between IL-10 and HCT (r = 0.37, p=0.012). In addition, data of other studied parameters are presented. In conclusion, IL-6 and IL-10 could be proposed for follow up of COVID-19 patients and to detect cases before progressing to a severe disease stage.

Novel VEGFR-2 inhibitors as antiangiogenic and apoptotic agents via paracrine and autocrine cascades: Design, synthesis, and biological evaluation.

Appertaining to its paracrine and autocrine signaling loops, VEGFR-2 succeeded in grabbing attention as one of the leading targets in cancer treatment. Based on the foregoing and our comprehensive studies regarding pharmacophoric features and activity of sorafenib, novel phenylpyridazinone based VEGFR-2 inhibitors 4, 6a-e, 7a,b, 9a,b, 12a-c, 13a,b, 14a,b, 15a,b, and 17a-d were optimized. An assortment of biological assays was conducted to assess the antiangiogenic and apoptotic activities of the synthesized derivatives. In vitro VEGFR-2 kinase assay verified the inhibitory activity of the synthesized derivatives with IC50 values from 49.1 to 418.0 nM relative to the reference drug sorafenib (IC50 = 81.8 nM). Antiproliferative activity against HUVECs revealed that compounds 2-{2-[2-(6-oxo-3-phenylpyridazin-1(6H)-yl)acetyl]hydrazineyl}-N-(p-tolyl)acetamide (12c) and 2-[(5-mercapto-4-methyl-4H-1,2,4-triazol-3-yl)methyl]-6-phenylpyridazin-3(2H)-one (13a) possessed superior activity (IC50 values = 11.5 and 12.3 nM, respectively) in comparison to sorafenib (IC50 = 23.2 nM). For the purpose of appraising their antiproliferative effect, derivatives 12c and 13a were exposed to cell cycle analysis, apoptotic, cell invasion and migration assays in addition to determination of VEGFR-2 in protein level. Moreover, cytotoxicity as well as selectivity index against WI-38 cell line was measured to examine safety of derivatives 12c and 13a. After that, molecular docking study was executed on the top five compounds in the in vitro VEGFR-2 kinase assay 6d, 12c, 13a, 14a and 17c to get a deep perception on binding mode of the synthesized compounds and correlate the design strategy with biological results. Finally, physicochemical, pharmacokinetic properties, and drug-likeness studies were performed on the top five derivative in in vitro VEGFR-2 kinase assay.