Approaches based on miRNAs in Behçet's Disease: Unveiling pathogenic mechanisms, diagnostic strategies, and therapeutic applications.

Behçet's Disease (BD) is an intricate medical puzzle, captivating researchers with its enigmatic pathogenesis. This complex ailment, distinguished by recurrent mouth and genital lesions, eye irritation, and skin injuries, presents a substantial obstacle to therapeutic research. This review explores the complex interaction of microRNAs (miRNAs) with BD, highlighting their crucial involvement in the disease's pathophysiology. miRNAs, recognized for regulatory influence in diverse biological processes, hold a pivotal position in the molecular mechanisms of autoimmune diseases, such as BD. The exploration begins with examining miRNA biogenic pathways and functions, establishing a foundational understanding of their regulatory mechanisms. Shifting to the molecular landscape governing BD, the review highlights miRNA-mediated impacts on critical signaling pathways like Notch, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and protein kinase B (AKT)/mammalian target of rapamycin (mTOR), offering insights into intricate pathophysiological mechanisms. Dissecting the immunological landscape reveals the profound influence of miRNAs on BD, shedding light on the intricate modulation of immune responses and offering novel perspectives on disease etiology and progression. Beyond molecular intricacies, the review explores the clinical relevance of miRNAs in BD, emphasizing their potential as diagnostic and prognostic indicators. The discussion extends to the promising realm of miRNA-based therapeutic interventions, highlighting their potential in alleviating symptoms and altering disease progression. This comprehensive review, serving as a valuable resource for researchers, clinicians, and stakeholders, aims to decipher the intricate molecular tapestry of BD and explore the therapeutic potential of miRNAs.

Exploring the sedative properties of natural molecules from hop cones (Humulus lupulus) as promising natural anxiolytics through GABA receptors and the human serotonin transporter.

This research work aimed to identify the main components that are responsible for the sedative properties of hop cones and allocate their targets. This investigation was performed through molecular docking, molecular dynamic simulations, root mean square fluctuation (RMSF) analysis, and DFT calculation techniques. The tested compounds from Humulus lupulus were compared to diazepam and paroxetine. Molecular docking showed that two-thirds of the compounds had a good affinity to gamma-aminobutyric acid (GABA), outperforming diazepam, while only three surpassed paroxetine on the SERT. Compounds 3,5-dihydroxy-4,6,6-tris(3-methylbut-2-en-1-yl)-2-(3-methylbutanoyl)cyclohexa-2,4-dien-1-one (5) and (S,E)-8-(3,7-dimethylocta-2,6-dien-1-yl)-5,7-dihydroxy-2-(4-hydroxyphenyl)chromen-4-one (15) showed stable binding and favorable energy parameters, indicating their potential for targeting GABA receptors and the SERT. This study provides a basis for future clinical research on these promising compounds.

A Retrospective Exploration of Pre-operative Antibiotic Prophylaxis with Cefazolin in Cesarean Sections: Implications for Obstetrics and Gynecologic Surgery.

Background: Post-partum infection is a major contributor to maternal mortality and is responsible for approximately 10% of maternal fatalities worldwide. The risk of infection is substantially higher in cesarean section procedures. Approximately 8% of women who undergo cesarean sections are susceptible to infection. Although the body of evidence supporting the regular pre-operative utilization of prophylactic antibiotic treatment is steadily expanding, its usefulness in cesarean sections has not yet been standardized, and post-partum infection is still a serious medical challenge. We aimed to retrospectively assess the prophylactic effectiveness of cefazolin in combination with other antibiotic agents in cesarean sections. Materials and Methods: Both uni-variable and multi-variable analyses were conducted to identify factors that may affect cefazolin pre-operative antibiotic prophylaxis in elective cesarean section operations. The uni-variable analysis included timing of administration, operation duration, body mass index (BMI), and wound type. A multi-variable logistic regression model was then created to determine which variables provide independent information in the context of other variables. Results: Time of administration did not affect prophylactic cefazolin efficacy. However, prophylactic cefazolin was 1.43 and 1.77 times more effective when the operation lasted for 45 minutes or more, compared with operations that were shorter than 45 minutes. Patients with a BMI ranging from 18 to 29 kg/m2 showed increased efficacy of prophylactic cefazolin compared with obese patients with a BMI exceeding 30 kg/m2. The effectiveness of prophylactic cefazolin decreased by 95% in patients with clean-contaminated surgical incisions compared with those with clean surgical incisions. Conclusions: Our findings demonstrate that administering pre-operative prophylactic antibiotic agents to women undergoing cesarean section resulted in a reduction in post-partum infections, thereby reducing maternal mortality. Furthermore, optimal timing of administration, re-dosing if necessary, length of prophylactic medication, and dosing adjustments for obese patients are crucial factors in preventing surgical site infections and promoting antimicrobial stewardship.

In silico molecular screening of bioactive natural compounds of rosemary essential oil and extracts for pharmacological potentials against rhinoviruses.

Rhinoviruses (RVs) cause upper respiratory tract infections and pneumonia in children and adults. These non-enveloped viruses contain viral coats of four capsid proteins: VP1, VP2, VP3, and VP4. The canyon on VP1 used cell surface receptor ICAM-1 as the site of attachment and for the internalization of viruses. To date, there has been no drug or vaccine available against RVs. In this study, bioactive natural compounds of rosemary (Salvia rosmarinus L.), which are known for their pharmacological potential, were considered to target the VP1 protein. A total of 30 bioactive natural compounds of rosemary were taken as ligands to target viral proteins. The PkCSM tool was used to detect their adherence to Lipinski's rule of five and the ADMET properties of the selected ligands. Further, the CB-Dock tool was used for molecular docking studies between the VP1 protein and ligands. Based on the molecular docking and ADMET profiling results, phenethyl amine (4 methoxy benzyl) was selected as the lead compound. A comparative study was performed between the lead compound and two antiviral drugs, Placonaril and Nitazoxanide, to investigate the higher potential of natural compounds over synthetic drugs. Placonaril also targets VP1 but failed in clinical trials while Nitazoxanide was examined in clinical trials against rhinoviruses. It was discovered from this study that the (4 methoxy benzyl) phenethyl amine exhibited less toxicity in comparison to other tested drugs against RVs. More research is needed to determine its potential and make it a good medication against RVs.

Fe3O4-Coated CNTs-Gum Arabic Nano-Hybrid Composites Exhibit Enhanced Anti-Leukemia Potency Against AML Cells via ROS-Mediated Signaling.

Background: Prior studies on magnetite (Fe3O4) NPs and carbon nanotubes (CNTs) cytotoxic effects against acute myeloid leukemia (AML) are inconclusive rather than definitive. Purpose: Investigation of the effects of Gum Arabic (GA)-stabilized/destabilized Fe3O4 NPs and CNTs, alone or in combination, on AML cell proliferation. Methods: Hybrid NPs were synthesized, characterized, and assessed for their cytotoxicity against Kasumi-1, HL-60, and THP-1 in comparison to normal primary bone marrow CD34+ cells. The molecular pathways of nanostructures' cytotoxicity were also investigated. Results: The Fe3O4 NPs were effectively synthesized and attached to the surface of the CNTs, resulting in the formation of a novel hybrid through their interaction with the GA colloidal solution in an aqueous media. Although the evaluated nanostructured nanoparticles had significant growth suppression ability against the leukemia cell lines, with IC50 values ranging from 42.437 to 189.842 µg/mL, they exhibited comparatively modest toxicity towards normal hematopoietic cells (IC50: 113.529‒162.656 µg/mL). The incorporation of Fe3O4 NPs with CNTs in a hybrid nanocomposite significantly improved their effectiveness against leukemia cells, with the extent of improvement varying depending on the specific cell type. The nanostructured particles were stabilized by GA, which enhances their ability to inhibit cell proliferation in a manner that depends on the specific cell type. Also, nanoparticles exhibit cytotoxicity due to their capacity to stimulate the production of intracellular ROS, halt the cell cycle at the G1 phase, and induce apoptosis. This is supported by the activation of p53, BAX, cytochrome C, and caspase-3, which are triggered by ROS. The nanostructures lead to an increase in the expression of genes encoding proteins related to oxidative stress (SIRT1, FOXO3, NFE2L2, and MAP3K5) and cyclin-dependent kinase inhibitors (CDKN1A and CDKN1B) in response to ROS. Conclusion: We provide an effective Fe3O4 NPs/CNTs nano-hybrid composite that induces apoptosis and has strong anti-leukemic capabilities. This hybrid nanocomposite is promising for in vivo testing and validation.

Biological Control of Tomato Bacterial Leaf Spots and Its Impact on Some Antioxidant Enzymes, Phenolic Compounds, and Pigment Content.

Tomato bacterial spots, caused by Xanthomonas campestris pv. vesicatoria (Xcv1) and X. euvesicatoria (Xe2), as well as bacterial specks, caused by two strains of Pseudomonas syringae pv. tomato (Pst1 and Pst2), represent significant threats to tomato production in the El-Sharkia governorate, often resulting in substantial yield losses. The objective of this study was to evaluate the efficacy of various biocontrol culture filtrates, including bacteria and fungi agents, in managing the occurrence and severity of these diseases, while also monitoring physiological changes in tomato leaves, including antioxidant enzymes, phenolics, and pigment content. The culture filtrates from examined Trichoderma species (T. viride, T. harzianum, and T. album), as well as the tested bacteria (Bacillus subtilis, Pseudomonas fluorescens, and Serratia marcescens) at concentrations of 25%, 50%, and 100%, significantly inhibited the proliferation of pathogenic bacteria In vitro. For the In vivo experiments, we used specific doses of 5 mL of spore suspension per plant for the fungal bioagents at a concentration of 2.5 × 107 spores/mL. The bacterial bioagents were applied as a 10 mL suspension per plant at a concentration of 1 × 108 CFU/mL. Spraying the culture filtrates of the tested bioagents two days before infection In vivo significantly reduced disease incidence and severity. Trichoderma viride exhibited the highest efficacy among the fungal bioagents, followed by T. harzianum and T. album. Meanwhile, the culture filtrate of B. subtilis emerged as the most potent among the bacterial bioagents, followed by P. fluorescens. Furthermore, applying these culture filtrates resulted in elevated levels of chitinase, peroxidase, and polyphenol oxidase activity. This effect extended to increased phenol contents, as well as chlorophyll a, chlorophyll b, and carotenoids in sprayed tomato plants compared to the control treatment. Overall, these findings underscore the potential of these biocontrol strategies to effectively mitigate disease incidence and severity while enhancing plant defense mechanisms and physiological parameters, thus offering promising avenues for sustainable disease management in tomato production.

Investigating Sulforaphane's anti-virulence and anti-quorum sensing properties against Pseudomonas aeruginosa.

Background: P. aeruginosa, a significant bacterium, can cause severe illness and resistance to antibiotics. Quorum sensing (QS) systems regulate virulence factors production. Targeting QS could reduce bacteria pathogenicity and prevent antibiotic resistance. Cruciferous vegetables contain sulforaphane, known for its anti-inflammatory, antioxidant, anticancer, and antimicrobial properties. Aim: We aimed to examine the inhibitory influences of sulforaphane, at a sub-inhibitory concentration (» minimum inhibitory concentration, MIC), on virulence and QS in P. aeruginosa. Materials and methods: The sulforaphane's anti-virulence actions at sub-inhibitory concentrations were explored in vitro and in vivo. A sub-MIC concentration of sulforaphane was combined with anti-pseudomonal drugs, and the results of this combination were assessed. The virtual affinity of sulforaphane for the receptors of QS was studied, and its effect on the expression of QS genes was quantified. Results: Sulforaphane significantly decreased the biofilm formation, motility, ability to withstand oxidative stress, and the synthesis of virulence extracellular enzymes such as proteases, hemolysins, and elastase, as well as other virulence factors like pyocyanin. In addition, sulforaphane lessened the severity of P. aeruginosa infection in mice. Sulforaphane reduced the antipseudomonal antibiotics' MICs when used together, resulting in synergistic effects. The observed anti-virulence impacts were attributed to the ability of sulforaphane to inhibit QS via suppressing the QS genes' expression. Conclusion: Sulforaphane shows promise as a potent anti-virulence and anti-QS agent that can be used alongside conventional antimicrobials to manage severe infections effectively. Furthermore, this study paves the way for further investigation of sulforaphane and similar structures as pharmacophores for anti-QS candidates.

Effect of Slow Maxillary Expansion and Alternative Rapid Maxillary Expansion Protocols on Airway Volume in Cleft Palate Cases: A Cone Beam Computed Tomography Based Study.

A total of 22 patients with cleft palate aged 8 to 12 years were selected and categorized into two groups: the first group was treated with alternate rapid maxillary expansion and constriction (Alt-RAMEC) using an expander with differential opening (EDO) and facemask, while the second group was treated using slow maxillary expansion (SME) using an EDO. Finally, the pharyngeal airway volume in the two groups was compared using cone beam computed tomography (CBCT). CBCT scans were performed before expansion and six months following the expansion. Alveolar crest level, maxillary breadth, nasal cavity width, arch width, inclination of the molar teeth, buccal and palatal alveolar bone thickness, and maxillary alveolar width were all assessed. Paired t-tests (p=0.05) were applied to compare interphase data. The two groups showed a non-significant difference in terms of nasopharyngeal volume (cm3), oropharyngeal volume (cm3), and overall pre- and post-treatment results (p>0.005). Results of comparison of pre- and post-treatment periods in the Alt-RAMEC group revealed a significantly higher cleft volume (cm3) (p=0.001). Results of comparison of pre- and post-treatment periods in the SME group revealed a substantial rise in cleft volume (cm3) (p=0.003). Results from a comparison of the cleft volume (cm3) between the two study groups pre- and post-intervention revealed a non-significant difference (p=0.200 and 0.054, respectively).

Improving the bioavailability and therapeutic efficacy of felodipine for the control of diabetes-associated atherosclerosis: In vitro and in vivo characterization.

Felodipine has proven to be effective as an atherosclerosis therapy because it increases blood flow to the vessel wall. However, the poor solubility, low bioavailability, and hepatic first-pass metabolism of oral felodipine compromise its therapeutic effectiveness. The study's goal is to create a nasal pH-sensitive hydrogel of felodipine-loaded invasomes (IPHFI) that will improve felodipine's release, permeation, bioavailability, and efficacy as a potential diabetes-associated atherosclerosis therapy. According to the pre-formulation study, the felodipine-loaded invasomes formulation composed of phospholipid (3%w/v), cholesterol (0.16%w/v), ethanol (3%v/v) and cineole (1%v/v) was chosen as the optimum formulation. The optimum formulation was characterized in vitro and then mixed with a mixture of chitosan and glyceryl monooleate to make the IPHFI formulation. The IPHFI formulation enhanced the release and permeation of felodipine by 2.99 and 3-fold, respectively. To assess the efficacy and bioavailability of the IPHFI formulation, it was studied in vivo using an experimental atherosclerosis rat model. Compared to oral free felodipine, the nasal administration of the IPHFI formulation increased the bioavailability by 3.37-fold and decreased the serum cholesterol, triglycerides, LDL, and calcification score by 1.56, 1.53, 1.80, and 1.18 ratios, respectively. Thus, nasal IPHFI formulation may represent a promising diabetes-associated atherosclerosis therapy.

An epigenetically distinct HSC subset supports thymic reconstitution.

Hematopoietic stem cells (HSCs) with multilineage potential are critical for effective T cell reconstitution and restoration of the adaptive immune system after allogeneic Hematopoietic Cell Transplantation (allo-HCT). The Kit lo subset of HSCs is enriched for multipotential precursors, 1, 2 but their T-cell lineage potential has not been well-characterized. We therefore studied the thymic reconstituting and T-cell potential of Kit lo HSCs. Using a preclinical allo-HCT model, we demonstrate that Kit lo HSCs support better thymic recovery, and T-cell reconstitution resulting in improved T cell responses to infection post-HCT. Furthermore, Kit lo HSCs with augmented BM lymphopoiesis mitigate age-associated thymic alterations, thus enhancing T-cell recovery in middle-aged hosts. We find the frequency of the Kit lo subset declines with age, providing one explanation for the reduced frequency of T-competent HSCs and reduced T-lymphopoietic potential in BM precursors of aged mice. 3, 4, 5 Chromatin profiling revealed that Kit lo HSCs exhibit higher activity of lymphoid-specifying transcription factors (TFs), including Zbtb1 . Deletion of Zbtb1 in Kit lo HSCs diminished their T-cell potential, while reinstating Zbtb1 in megakaryocytic-biased Kit hi HSCs rescued T-cell potential, in vitro and in vivo . Finally, we discover an analogous Kit lo HSC subset with enhanced lymphoid potential in human bone marrow. Our results demonstrate that Kit lo HSCs with enhanced lymphoid potential have a distinct underlying epigenetic program.

Outcomes of Head and Neck Neurogenic Tumors.

BACKGROUND: Lateral neck mass management frequently challenges surgeons. Nerve tissue neoplasms are an uncommon cause of such nodules. Neurogenic tumors form a tiny percentage of the head and neck neoplastic lesions. Considering the number of nerves in this area, it is surprising that such neoplasms are not more frequently seen. METHODS: A retrospective study was conducted on all patients who presented to the National Cancer Institute of Cairo, Egypt, with head and neck neurogenic neoplasms. RESULTS: During the last 10 years at the National Cancer Institute of Egypt (2006-2015), 40 cases of neurogenic tumors of the head and neck were treated at the head and neck unit. Patients' ages ranged from two to 78 years with a mean age of 34.7 years. Childhood neurogenic tumors accounted for nine cases (22.5%) only in this study. Male patients diagnosed with these tumors comprised 16 cases, while female patients comprised 24 cases, with a female-to-male ratio of 1.5:1. Patient presentation depends on the biological behavior of the tumor; for instance, some of them present by slowly growing painless well-circumscribed mobile swelling, and others present by rapidly growing swelling with neurological deficit. Clinical picture and imaging studies such as CT and MRI raise suspicion and may help delineate such tumors, but a definitive diagnosis is obtained by tissue biopsy. Surgery is the mainstay of treatment in most head and neck neurogenic tumors, whereas adjuvant therapy is of limited benefit in some types of neurogenic tumors. The five-year survival rate was 60% for the malignant group, while death was reported in six out of 15 cases (40%).  Conclusion: Most neurogenic head and neck tumors are benign. Accurate preoperative assessment and a high degree of suspicion are the initial steps in the management. Proper treatment involves complete surgical excision; however, debulking procedures have an important role. Malignant neurogenic tumors are aggressive and are treated with combined radical surgical resection and radiation. Chemotherapy is tried for locally advanced unresectable or metastatic disease.

Comparative metabolomics analysis of Citrus medica var. sarcodactylis Swingle and Limonia acidissima Linn. Fruits and leaves cultivated in Egypt in context to their antiviral effects.

A comprehensive study of fruits and leaves extracts of Citrus medica var. sarcodactylis Swingle and Limonia acidissima L. family Rutaceae was accomplished to investigate their antiviral activity along with their zinc oxide nanoparticles formulation (ZnONPs) against the avian influenza H5N1 virus. A thorough comparative phytochemical investigation of C. medica and L.acidissima leaves and fruits was performed using UPLC-QTOF-MS-MS. Antiviral effects further aided by molecular docking proved the highly significant potential of using C. medica and L.acidissima extracts as medicinal agents. Antiviral potency is ascendingly arranged as L. acidissima leaves (LAL) > L. acidissima fruits (LAF) > C. medica leaves (CML) at 160 µg. Nano formulation of LAF has the most splendid antiviral upshot. The metabolomic profiling of CMF and LAL revealed the detection of 48 & 74 chromatographic peaks respectively. Docking simulation against five essential proteins in survival and replication of the influenza virus revealed that flavonoid di-glycosides (hesperidin, kaempferol-3-O-rutinoside, and kaempferol-7-neohesperidoside) have shown great affinity toward the five investigated proteins and achieved docking scores which approached or even exceeded that achieved by the native ligands. Hesperidin has demonstrated the best binding affinity toward neuraminidase (NA), haemagglutinin (HA), and polymerase protein PB2 (-10.675, -8.131, and -10.046 kcal/mol respectively. We propose using prepared crude methanol extracts of both plants as an antiviral agent.

Probing protein aggregation through spectroscopic insights and multimodal approaches: A comprehensive review for counteracting neurodegenerative disorders.

Aberrant accumulation of protein misfolding can cause aggregation and fibrillation and is one of the primary characteristic features of neurodegenerative diseases. Because they are disordered, misfolded, and aggregated proteins pose a significant setback in drug designing. The structural study of intermediate steps in these kinds of aggregated proteins will allow us to determine the conformational changes as well as the probable pathways encompassing various neurodegenerative disorders. The analysis of protein aggregates involved in neurodegenerative diseases relies on a diverse toolkit of biophysical techniques, encompassing both morphological and non-morphological methods. Additionally, Thioflavin T (ThT) assays and Circular Dichroism (CD) spectroscopy facilitate investigations into aggregation kinetics and secondary structure alterations. The collective application of these biophysical techniques empowers researchers to comprehensively unravel the intricate nature of protein aggregates associated with neurodegeneration. Furthermore, the topics covered in this review have summed up a handful of well-established techniques used for the structural analysis of protein aggregation. This multifaceted approach advances our fundamental understanding of the underlying mechanisms driving neurodegenerative diseases and informs potential therapeutic strategies.

Eco-friendly optical sensor for precise detection of gold ions in diverse matrices through the integration of ß-2-hydroxybenzyl-3-methoxy-2-hydroxyazastyrene in a PVC membrane.

An environmentally conscious methodology is investigated for the precise and discerning identification of trace concentrations of gold ions in diverse matrices. A novel optical sensor membrane is proposed for the determination of Au3+ ions, utilizing the immobilization of ß-2-hydroxybenzyl-3-methoxy-2-hydroxyazastyrene (HMHS) entrapped in polyvinyl chloride (PVC). The sensor incorporates sodium tetraphenylborate (Na-TPB) as the ionic additive and dibutyl phthalate (DBP) as a plasticizer. Under optimal conditions, the suggested sensor exhibits a linear calibration response to Au3+ ions within a concentration range of 5.0 to 165 ng mL-1. Detection and quantification limits are specified as 1.5 and 4.8 ng mL-1, respectively, with a rapid response time of 5.0 min. Upon presentation, this optical sensor not only affirms high reproducibility, stability, and an extended operational lifespan but also showcases exceptional selectivity for Au3+ ions. Notably, no discernible interference is observed when assessing the potential influence of other cations and anions on Au3+ ion detection. The adaptability of this optical sensor is validated through its successful application in determining Au3+ ion concentrations across various sample types, including water, environmental, cosmetics, and soil matrices.

Revolutionizing scandium detection in real samples: Unleashing the power of sol-gel-based optical sensor.

The development of a highly selective and ultra-sensitive optical sensor for detecting scandium (Sc3+) ions involves incorporating the reagent 2,3-dichloro-6-(3-carboxy-2-hydroxy-1-naphthylazo)quinoxaline (DCHNAQ) into a silica sol-gel thin film on a glass substrate. This innovative approach utilizes tetraethoxy-silane (TEOS) as the precursor, maintaining a sol-gel pH level of 4.5, a water-to-alkoxide ratio of 5:1, and a DCHNAQ concentration of 5.0 × 10-4 M. A detailed exploration of the impact of sol-gel parameters on the sensing capabilities of the developed sensor has been meticulously undertaken. This innovative sensor demonstrates remarkable selectivity in evaluating Sc3+ ions over a dynamic range of 7.5-170 ng/mL, with limits of quantification and detection recorded at 7.3 and 2.20 ng/mL, respectively. Consistent results are achieved with a minimal RSD of 1.47 and 0.94% for Sc3+ ions at 50 and 100 ng/mL, respectively, coupled with a swift response time of three min. Assessments of interference demonstrate a noteworthy preference for Sc3+ions, accomplished by enclosing DCHNAQ within the sol-gel framework and making optimal structural modifications to the doped sol-gel. The sensor offers straightforward regeneration using a 0.25 M EDTA solution, exhibiting complete reversibility. Comparative analysis with other methodologies underscores the efficacy in determining Sc3+ions in various reference materials, including plant leaves, fish, water, alloys, ores, and monazite samples.

Bat-borne H9N2 influenza virus evades MxA restriction and exhibits efficient replication and transmission in ferrets.

Influenza A viruses (IAVs) of subtype H9N2 have reached an endemic stage in poultry farms in the Middle East and Asia. As a result, human infections with avian H9N2 viruses have been increasingly reported. In 2017, an H9N2 virus was isolated for the first time from Egyptian fruit bats (Rousettus aegyptiacus). Phylogenetic analyses revealed that bat H9N2 is descended from a common ancestor dating back centuries ago. However, the H9 and N2 sequences appear to be genetically similar to current avian IAVs, suggesting recent reassortment events. These observations raise the question of the zoonotic potential of the mammal-adapted bat H9N2. Here, we investigate the infection and transmission potential of bat H9N2 in vitro and in vivo, the ability to overcome the antiviral activity of the human MxA protein, and the presence of N2-specific cross-reactive antibodies in human sera. We show that bat H9N2 has high replication and transmission potential in ferrets, efficiently infects human lung explant cultures, and is able to evade antiviral inhibition by MxA in transgenic B6 mice. Together with its low antigenic similarity to the N2 of seasonal human strains, bat H9N2 fulfils key criteria for pre-pandemic IAVs.

Cross-species spill-over potential of the H9N2 bat influenza A virus.

In 2017, a novel influenza A virus (IAV) was isolated from an Egyptian fruit bat. In contrast to other bat influenza viruses, the virus was related to avian A(H9N2) viruses and was probably the result of a bird-to-bat transmission event. To determine the cross-species spill-over potential, we biologically characterize features of A/bat/Egypt/381OP/2017(H9N2). The virus has a pH inactivation profile and neuraminidase activity similar to those of human-adapted IAVs. Despite the virus having an avian virus-like preference for α2,3 sialic acid receptors, it is unable to replicate in male mallard ducks; however, it readily infects ex-vivo human respiratory cell cultures and replicates in the lungs of female mice. A/bat/Egypt/381OP/2017 replicates in the upper respiratory tract of experimentally-infected male ferrets featuring direct-contact and airborne transmission. These data suggest that the bat A(H9N2) virus has features associated with increased risk to humans without a shift to a preference for α2,6 sialic acid receptors.

HPLC-ESI/MS-MS metabolic profiling of white pitaya fruit and cytotoxic potential against cervical cancer: Comparative studies, synergistic effects, and molecular mechanistic approaches.

Natural approach became a high demand for the prevention and treatment of such diseases for their proven safety and efficacy. This study is aimed to perform comparative phytochemical analysis of white pitaya (Hylocereus undatus) peel, pulp and seed extracts via determination of total flavonoid content, phenolic content, and antioxidant capacity, coupled with HPLC-ESI/MS-MS analysis. Further, we evaluated the synergistic cytotoxic potential with Cisplatin against cervical cancer cells with investigation of underlying mechanism. The highest content of phenolics and antioxidants were found in both seed and peel extracts. The HPLC-ESI/MS-MS revealed identification of flavonoids, phenolic acids, anthocyanin glycosides, lignans, stilbenes, and coumarins. The cytotoxicity effects were evaluated by MTT assay against prostate, breast and cervical (HeLa) and Vero cell lines. The seed and peel extracts showed remarkable cytotoxic effect against all tested cell lines. Moreover, the selectivity index confirmed high selectivity of pitaya extracts to cancer cells and safety on normal cells. The combined therapy with Cisplatin effectively enhanced its efficacy and optimized the treatment outcomes, through the apoptotic ability of pitaya extracts in HeLa cells, as evaluated by flow cytometry. Besides, RT-PCR and western blotting analysis showed downregulation of Bcl-2 and overexpression of P53, BAX among HeLa cells treated with pitaya extracts, which eventually activated apoptosis process. Thus, pitaya extract could be used as adjuvant therapy with cisplatin for treatment of cervical cancer. Furthermore, in-vivo extensive studies on the seed and peel extracts, and their compounds are recommended to gain more clarification about the required dose, and side effects.

Disease prognosis and therapeutic strategies in patients with advanced non-small cell lung cancer (NSCLC): a 6-year epidemiological study between 2015-2021.

Background: Lung cancer is the top cause of mortality in males and the second largest cause of cancer-related fatalities in women worldwide. Non-small cell lung cancer (NSCLC) cases are discovered at an advanced stage, raising major challenges in disease management and survival outcomes. This study aimed to investigate the clinical findings and management of stage IIIB and IV NSCLC patients for better decision-making, disease management, and understanding of this fatal disease. Methods: In this cohort study of 340 patients, a total of 140 (41.2%) were diagnosed with advanced-stage NSCLC at a mean age of 64 years. The electronic data of patients from 2015 to 2021 who met the inclusion criteria were retrieved from two tertiary hospitals in Riyadh, Saudi Arabia, and an Excel sheet was used to record the variables. Patients' data including all categorical variables such as gender, stage, metastasis, ALK, EGFR, and ROS, etc., and continuous variables such as age and body mass index (BMI) were retrieved and analyzed. Results: The multivariate Cox-regression model indicated that smoking was the significant risk factor of death for two-thirds of male smokers (37.9%), with a median survival time of 123 days. Disease progression was higher with pleural and brain metastasis, and localized metastasis was the highest in 75% of patients. The intent of treatment was mainly palliative, however, a statistically significant association was found with the simultaneous use of chemotherapy and immunotherapy. Patients' response to first-line treatment revealed a significant improvement if chemotherapy treatment was maintained at the same dose without interruption of dosage. Conclusions: The overall cure and survival rates for NSCLC remain low, particularly in metastatic disease. Therefore, continued research into new drugs and combination therapies is required for better decision-making to expand the clinical benefit to a broader patient population and to improve outcomes in NSCLC.

Risk of Ovarian Malignancy Algorithm and Pelvic Mass Score for the prediction of malignant ovarian tumors: a prospective comparative study.

Aim: Ovarian cancer is the seventh most common female cancer worldwide. Nevertheless, there is no available universal screening method for malignant ovarian masses. This study compares the value of the Risk of Ovarian Malignancy Algorithm (ROMA) and Pelvic Mass Score (PMS) scoring systems in the diagnosis of malignant ovarian masses. Material and methods: This prospective comparative study was conducted from March 2021 until April 2022. A total of 258 women diagnosed with ovarian mass and eligible for surgical intervention according to institutional guidelines were enrolled in the study. Ultrasound was performed for the assessment of masses, ascites and metastases, also color flow Doppler was done to measure the resistance index of the mass vasculature. Preoperative venous blood samples were collected to measure CA 125 and HE4. PMS and ROMA scoring systems were calculated for each patient. All women were subjected to a surgical intervention (according to applicable institutional guidelines), using either open or laparoscopic techniques. Histopathological examination of the removed specimens was done, and in line with the recognized gold standard, the results were compared with the pre-operative diagnosis of both scoring systems. Results: Both PMS and ROMA showed a high predictive probability for ovarian malignancies (AUC = 0.93, sensitivity = 83.3%, specificity = 90.37%; AUC = 0.91, sensitivity = 84.4%, specificity = 95.56%, respectively), yet no statistical significant difference was found between the two scoring systems (p = 0.353, 95% CI -0.025 to 0.070). Conclusions: Both PMS and ROMA seem to be promising scoring systems for discriminating benign from malignant ovarian masses, but more research is needed to determine the optimum diagnostic pathway, especially one yielding the least false-negative results.