Development of machine learning models for forecasting the strength of resilient modulus of subgrade soil: genetic and artificial neural network approaches.

Accurately predicting the Modulus of Resilience (MR) of subgrade soils, which exhibit non-linear stress-strain behaviors, is crucial for effective soil assessment. Traditional laboratory techniques for determining MR are often costly and time-consuming. This study explores the efficacy of Genetic Programming (GEP), Multi-Expression Programming (MEP), and Artificial Neural Networks (ANN) in forecasting MR using 2813 data records while considering six key parameters. Several Statistical assessments were utilized to evaluate model accuracy. The results indicate that the GEP model consistently outperforms MEP and ANN models, demonstrating the lowest error metrics and highest correlation indices (R2). During training, the GEP model achieved an R2 value of 0.996, surpassing the MEP (R2 = 0.97) and ANN (R2 = 0.95) models. Sensitivity and SHAP (SHapley Additive exPlanations) analysis were also performed to gain insights into input parameter significance. Sensitivity analysis revealed that confining stress (21.6%) and dry density (26.89%) are the most influential parameters in predicting MR. SHAP analysis corroborated these findings, highlighting the critical impact of these parameters on model predictions. This study underscores the reliability of GEP as a robust tool for precise MR prediction in subgrade soil applications, providing valuable insights into model performance and parameter significance across various machine-learning (ML) approaches.

Unraveling the influence of LncRNA in gastric cancer pathogenesis: a comprehensive review focus on signaling pathways interplay.

Gastric cancers (GCs) are among the most common and fatal malignancies in the world. Despite our increasing understanding of the molecular mechanisms underlying GC, further biomarkers are still needed for more in-depth examination, focused prognosis, and treatment. GC is one among the long non-coding RNAs, or lncRNAs, that have emerged as key regulators of the pathophysiology of cancer. This comprehensive review focuses on the diverse functions of long noncoding RNAs (lncRNAs) in the development of GC and their interactions with important intracellular signaling pathways. LncRNAs affect GC-related carcinogenic signaling cascades including pathways for EGFR, PI3K/AKT/mTOR, p53, Wnt/ß-catenin, JAK/STAT, Hedgehog, NF-κB, and hypoxia-inducible factor. Dysregulated long non-coding RNA (lncRNA) expression has been associated with multiple characteristics of cancer, such as extended growth, apoptosis resistance, enhanced invasion and metastasis, angiogenesis, and therapy resistance. For instance, lncRNAs such as HOTAIR, MALAT1, and H19 promote the development of GC via altering these pathways. Beyond their main roles, GC lncRNAs exhibit potential as diagnostic and prognostic biomarkers. The overview discusses CRISPR/Cas9 genome-modifying methods, antisense oligonucleotides, small molecules, and RNA interference as potential therapeutic approaches to regulate the expression of long noncoding RNAs (lncRNAs). An in-depth discussion of the intricate functions that lncRNAs play in the development of the majority of stomach malignancies is provided in this review. It provides the groundwork for future translational research in lncRNA-based whole processes toward GC by highlighting their carcinogenic effects, regulatory roles in significant signaling cascades, and practical scientific uses as biomarkers and therapeutic targets.

Association Between Rhesus and ABO Blood Group Types and Their Impact on Clinical Outcomes in Critically Ill Patients with COVID-19: A Multi-Center Investigation.

Background: There is increasing evidence suggesting that ABO blood type may play a role in the immunopathogenesis of COVID-19 infection. In addition to ABO blood type, the Rhesus (Rh) factor has also been implicated in various disease processes. Therefore, our study aimed to assess the association between both ABO and Rh blood types in critically ill patients with COVID-19 and their clinical outcomes. Methods: A multicenter retrospective cohort study conducted in Saudi Arabia between March 1, 2020, and July 31, 2021, involving adult COVID-19 patients admitted to Intensive Care Units, aimed to explore potential associations between rhesus blood group types (Positive versus Negative) and clinical outcomes. The primary endpoint assessed was the hospital length of stay (LOS). Other endpoints were considered secondary. Results: After propensity score matching (3:1 ratio), 212 patients were included in the final analysis. The hospital length of stay was longer in a negative Rh blood group compared with patients in the Rh-positive group (beta coefficient 0.26 (0.02, 0.51), p = 0.03). However, neither 30-day mortality (HR 0.28; 95% CI 0.47, 1.25, p = 0.28) nor in-hospital mortality (HR 0.74; 95% CI 0.48, 1.14, p = 0.17) reached statistical significance. Additionally, among the different ABO types, the A+ blood group exhibited a higher proportion of thrombosis/infarction and in-hospital mortality (28.1% and 31.2%, respectively). Conclusion: This study highlights the potential impact of blood group type on the prognosis of critically ill patients with COVID-19. It has been observed that patients with a negative Rh blood group type tend to have a longer hospital stay, while their mortality rates and complications during ICU stay are similar to the patients with a Rh-positive group.

A novel vaccine construct against Zika virus fever: insights from epitope-based vaccine discovery through molecular modeling and immunoinformatics approaches.

The Zika virus (ZIKV) is an emerging virus associated with the Flaviviridae family that mainly causes infection in pregnant women and leads to several abnormalities during pregnancy. This virus has unique properties that may lead to pathological diseases. As the virus has the ability to evade immune response, a crucial effort is required to deal with ZIKV. Vaccines are a safe means to control different pathogenic infectious diseases. In the current research, a multi-epitope-based vaccination against ZIKV is being designed using in silico methods. For the epitope prediction and prioritization phase, ZIKV polyprotein (YP_002790881.1) and flavivirus polyprotein (>YP_009428568.1) were targeted. The predicted B-cell epitopes were used for MHC-I and MHC-II epitope prediction. Afterward, several immunoinformatics filters were applied and nine (REDLWCGSL, MQDLWLLRR, YKKSGITEV, TYTDRRWCF, RDAFPDSNS, KPSLGLINR, ELIGRARVS, AITQGKREE, and EARRSRRAV) epitopes were found to be probably antigenic in nature, non-allergenic, non-toxic, and water soluble without any toxins. Selected epitopes were joined using a particular GPGPG linker to create the base vaccination for epitopes, and an extra EAAAK linker was used to link the adjuvant. A total of 312 amino acids with a molecular weight (MW) of 31.62762 and an instability value of 34.06 were computed in the physicochemical characteristic analysis, indicating that the vaccine design is stable. The molecular docking analysis predicted a binding energy of -329.46 (kcal/mol) for TLR-3 and -358.54 (kcal/mol) for TLR-2. Moreover, the molecular dynamics simulation analysis predicted that the vaccine and receptor molecules have stable binding interactions in a dynamic environment. The C-immune simulation analysis predicted that the vaccine has the ability to generate both humoral and cellular immune responses. Based on the design, the vaccine construct has the best efficacy to evoke immune response in theory, but experimental analysis is required to validate the in silico base approach and ensure its safety.

Designing an mRNA Vaccine against P. jirovecii Involved in Fatal Pneumonia Infections via Comparative Proteomics and Reverse Vaccinology Approaches.

BACKGROUND: Pneumocystis jirovecii is the most emerging life-threating health problem that causes acute and fatal pneumonia infection. It is rare and more contagious for patients with leukemia and immune-deficiency disorders. Until now there is no treatment available for this infection therefore, it is needed to develop any treatment against this pathogen. METHODS: In this work, we used comparative proteomics, robust immune-informatics, and reverse vaccinology to create an mRNA vaccine against Pneumocystis jirovecii by targeting outer and transmembrane proteins. Using a comparative subtractive proteomic analysis of two Pneumocystis jirovecii proteomes, a distinct non-redundant Pneumocystis jirovecii (strain SE8) proteome was chosen. Seven Pneumocystis jirovecii transmembrane proteins were chosen from this proteome based on hydrophilicity, essentiality, virulence, antigenicity, pathway interaction, protein-protein network analysis, and allergenicity. OBJECTIVE: The reverse vaccinology approach was used to predict the immunogenic and antigenic epitopes of major histocompatibility complex (MHC) I, II and B-cells from the selected proteins on the basis of their antigenicity, toxicity and allergenicity. These immunogenic epitopes were linked together to construct the mRNA-based vaccine. To enhance the immunogenicity, suitable adjuvant, linkers (GPGPG, KK, and CYY), and PRDRE sequences were used. RESULTS: Through predictive modeling and confirmation via the Ramachandran plot, we assessed secondary and 3D structures. The adjuvant RpfE was incorporated to enhance the vaccine construct's immunogenicity (GRAVY index: -0.271, instability index: 39.53, antigenicity: 1.0428). The physiochemical profiling of vaccine construct was predicted it an antigenic, efficient, and potential vaccine. Notably, strong interactions were observed between the vaccine construct and TLR-3/TLR-4 (-1301.7 kcal/mol-1 and -1374.7 kcal/mol-1). CONCLUSIONS: The results predicted that mRNA-based vaccines trigger a cellular and humoral immune response, making the vaccine potential candidate against Pneumocystis jirovecii and it is more suitable for in-vitro analysis and validation to prove its effectiveness.

Zinc oxide nanoparticles loaded with linalool as a potential control agent of malaria infection.

This research aimed to produce and analyze zinc oxide nanoparticles (ZNPs) loaded with linalool (LZNPs), and to evaluate their in vitro and in vivo efficacy through targeting the inflammation and oxidative stress. LZNPs were synthesized using an ethanolic solution of polyvinyl alcohol. The Malstat technique was used to evaluate the effectiveness of LZNPs against both sensitive and resistant strains of Plasmosium falciparum. In vivo effects of ZNPs and LZNPs on parasite growth suppression, survival rate, oxidative stress markers, antioxidant genes, and gene and protein levels of inflammatory cytokines were evaluated by Real-time PCR and Western blot techniques. The results indicated that LZNPs demonstrated noteworthy (P < 0.001) antiplasmodial activity against both susceptible and resistant strains of P. falciparum. P. berghei NK65 strain-infected mice treated with the ZNPs and LZNPs at doses of 5-15 mg/kg notably (p < 0.001) increased the survival rates and parasite growth suppression. LZNPs at 5-15 mg/kg demonstrated a significant (p < 0.001) decrease in oxidative stress markers, increased the expression level of antioxidant genes, and reduced the gene and protein expression level of inflammatory cytokines. The current experimental study demonstrated the potent in vitro antiplasmodial activity of LZNPs against chloroquine-resistant and sensitive strains of P. falciparum compared to ZNPs alone. Additionally, the study identified the potential benefits of this nanocomposite in suppressing the parasite and extending the survival rate in mice infected with P. berghei by targeting inflammation and oxidative stress. It also showed minimal toxicity in liver and kidney function in healthy mice. Nevertheless, further research is essential to elucidate the comprehensive mechanisms and practical effectiveness of LZNPs.

Association of Screen Time Exposure With Autism Spectrum Disorder in Four to Six-Year-Old Children in Arar City, Saudi Arabia.

Background Autism spectrum disorder (ASD) is a psychopathologic disorder caused by several factors. The early signs include poor interaction and communication, delayed milestones, and repeated behavior patterns. This study aimed to assess the relationship between screen time and ASD severity and investigate the types of electronic devices associated with ASD in children aged four to six years in Arar City, Kingdom of Saudi Arabia (KSA). Methodology A cross-sectional study was conducted in primary healthcare centers (PHCs) in Arar City, KSA. The study enrolled all parents with children aged four to six years attending the PHCs in Arar City, KSA. Results The total sample size was 199 participants. Regarding the relationship between screen time exposure and ASD, there were variable screen time exposure durations, with 22.6% of children exposed for less than an hour, 30.7% for one to two hours, and 46.7% for more than two hours. Moreover, the type of electronic devices to which children were exposed varied, with smartphones being the most prevalent (68.3%). In terms of the age of children since exposure to electronic devices, the data indicated that 30.2% were exposed before the age of two, 35.2% between two and three years, and 34.7% after three years of age. Regarding the relationship with sociodemographic characteristics, there was a statistically significant relationship with the mother's age at birth (p = 0.050), mother's education level (p = 0.009), father's education level (p = 0.049), whether the child was suffering from any chronic or neurological disease (p = 0.008), age since the child was exposed to electronic devices (p = 0.049), and screen time exposure duration (p = 0.040). Conclusions The study highlights the significant association between screen time exposure and the development of ASD in children. Public awareness of this associated risk among caregivers is recommended to follow the protective guidelines. Further research and interventions are needed to better understand and address the impact of screen media use on children's neurodevelopment and overall well-being.

High resolution mapping of a novel non-transgressive hybrid susceptibility locus in barley exploited by P. teres f. maculata.

Hybrid genotypes can provide significant yield gains over conventional inbred varieties due to heterosis or hybrid vigor. However, hybrids can also display unintended negative attributes or phenotypes such as extreme pathogen susceptibility. The necrotrophic pathogen Pyrenophora teres f. maculata (Ptm) causes spot form net blotch, which has caused significant yield losses to barley worldwide. Here, we report on a non-transgressive hybrid susceptibility locus in barley identified between the three parental lines CI5791, Tifang and Golden Promise that are resistant to Ptm isolate 13IM.3. However, F2 progeny from CI5791 × Tifang and CI5791 × Golden Promise crosses exhibited extreme susceptibility. The susceptible phenotype segregated in a ratio of 1 resistant:1 susceptible representing a genetic segregation ratio of 1 parental (res):2 heterozygous (sus):1 parental (res) suggesting a single hybrid susceptibility locus. Genetic mapping using a total of 715 CI5791 × Tifang F2 individuals (1430 recombinant gametes) and 149 targeted SNPs delimited the hybrid susceptibility locus designated Susceptibility to Pyrenophora teres 2 (Spt2) to an ~ 198 kb region on chromosome 5H of the Morex V3 reference assembly. This single locus was independently mapped with 83 CI5791 × Golden Promise F2 individuals (166 recombinant gametes) and 180 genome wide SNPs that colocalized to the same Spt2 locus. The CI5791 genome was sequenced using PacBio Continuous Long Read technology and comparative analysis between CI5791 and the publicly available Golden Promise genome assembly determined that the delimited region contained a single high confidence Spt2 candidate gene predicted to encode a pentatricopeptide repeat-containing protein.

Inhibitory effect and mechanism of oregano essential oil on Listeria monocytogenes cells, toxins and biofilms.

Listeria monocytogenes (L. monocytogenes) is a prevalent foodborne pathogen with a remarkable capacity to form biofilms on utensil surfaces. The Listeriolysin O (LLO) exhibits hemolytic activity, which is responsible for causing human infections. In this study, we investigated the inhibitory effect and mechanism of oregano essential oil (OEO) on L. monocytogenes, evaluated the effects on its biofilm removal and hemolytic activity. The minimum inhibitory concentration (MIC) of OEO against L. monocytogenes was 0.03 % (v/v). L. monocytogenes was treated with OEO at 3/2 MIC for 30 min the bacteria was decreased below the detection limit (10 CFU/mL) in PBS and TSB (the initial bacterial load was about 6.5 log CFU/mL). The level of L. monocytogenes in minced pork co-cultured with OEO (15 MIC) about 2.5 log CFU/g lower than that in the untreated group. The inhibitory mechanisms of OEO against planktonic L. monocytogenes encompassed perturbation of cellular morphology, elevation in reactive oxygen species levels, augmentation of lipid oxidation extent, hyperpolarization of membrane potential, and reduction in intracellular ATP concentration. In addition, OEO reduced biofilm coverage on the surface of glass slides by 62.03 % compared with the untreated group. Meanwhile, OEO (1/8 MIC) treatment reduced the hemolytic activity of L. monocytogenes to 24.6 % compared with the positive control. Molecular docking suggested carvacrol and thymol might reduce the hemolytic activity of L. monocytogenes. The results of this study demonstrate that OEO exhibits inhibitory effects against L. monocytogenes, biofilms and LLO, which had potential as natural antimicrobial for the inhibition of L. monocytogenes.

Optimizing the resveratrol fragments for novel in silico hepatocellular carcinoma de novo drug design.

Hepatocellular carcinoma (HCC) incidence varies widely around the world and is impacted by factors such as the prevalence of chronic hepatitis B and C infections, alcohol intake, and access to healthcare. The proteins (BRAF_human, VGFR3_human, EGFR_human and UFO_human) play a vital role in hepatocellular carcinoma prognosis, which involves cell proliferation, cell growth, transmission of extracellular signals to the cell nucleus and consequently regulating many other cellular processes. Fostamatinib has been studied for its possible use in the treatment of hepatocellular cancer because it is a more convenient therapy choice for patients and has minor side effects on the human body. However, resveratrol phytochemical has been investigated for its potential use in the prevention and treatment of a wide range of disorders, including cancer, cardiovascular disease, diabetes, and neurological problems due to its frequently antioxidant, anti-inflammatory, and immune-modulating characteristics, which can aid in the prevention of chronic illnesses. This study developed de novo-based fragment-optimized resveratrol (FOR), enhancing therapeutic potential and lowering toxicity. The docking study was performed with four target proteins, and the findings reveal that the vascular endothelial growth factor receptor 3 protein possessed the highest binding energy values of -7.6 kcal/mol with FOR. Additionally, it completely fulfills the criteria of drug-likeliness rules. Thus, FOR proves to be an efficient drug candidate for future in-vivo studies against hepatocellular carcinoma.

Natural products and long noncoding RNA signatures in gallbladder cancer: a review focuses on pathogenesis, diagnosis, and drug resistance.

Gallbladder cancer (GBC) is an aggressive and lethal malignancy with a poor prognosis. Long noncoding RNAs (lncRNAs) and natural products have emerged as key orchestrators of cancer pathogenesis through widespread dysregulation across GBC transcriptomes. Functional studies have revealed that lncRNAs interact with oncoproteins and tumor suppressors to control proliferation, invasion, metastasis, angiogenesis, stemness, and drug resistance. Curcumin, baicalein, oleanolic acid, shikonin, oxymatrine, arctigenin, liensinine, fangchinoline, and dioscin are a few examples of natural compounds that have demonstrated promising anticancer activities against GBC through the regulation of important signaling pathways. The lncRNAs, i.e., SNHG6, Linc00261, GALM, OIP5-AS1, FOXD2-AS1, MINCR, DGCR5, MEG3, GATA6-AS, TUG1, and DILC, are key players in regulating the aforementioned processes. For example, the lncRNAs FOXD2-AS1, DILC, and HOTAIR activate oncogenes such as DNMT1, Wnt/ß-catenin, BMI1, and c-Myc, whereas MEG3 and GATA6-AS suppress the tumor proteins NF-κB, EZH2, and miR-421. Clinically, specific lncRNAs can serve as diagnostic or prognostic biomarkers based on overexpression correlating with advanced TNM stage, metastasis, chemoresistance, and poor survival. Therapeutically, targeting aberrant lncRNAs with siRNA or antisense oligos disrupts their oncogenic signaling and inhibits GBC progression. Overall, dysfunctional lncRNA regulatory circuits offer multiple avenues for precision medicine approaches to improve early GBC detection and overcome this deadly cancer. They have the potential to serve as novel biomarkers as they are detectable in bodily fluids and tissues. These findings enhance gallbladder treatments, mitigating resistance to chemo- and radiotherapy.

Brace-related Stress and Quality of Life Parameters between Chêneau and Boston Braces: A Cross-sectional Comparative Study on Adolescent Idiopathic Scoliosis in Saudi Arabia.

OBJECTIVE: Adolescent idiopathic scoliosis (AIS) is the most prevalent spinal deformity affecting healthy children. Although AIS typically lacks symptomatic manifestations, its resultant deformities can affect patients' quality of life (QoL). Evaluating QoL and stress levels is crucial in determining the optimal brace type for AIS patients; however, research comparing the effectiveness of different brace types in this regard is lacking. Therefore, this study aimed to evaluate the impact of Boston versus Chêneau braces on QoL and stress levels in AIS patients. METHODS: This cross-sectional study was conducted at a medical institution in Riyadh, Saudi Arabia, involving 52 eligible patients selected through stratified random sampling based on type of brace as the main stratum. The inclusion criteria were idiopathic scoliosis, age ≥ 10 years, bracing for at least 3 months, and no history of cancer. QoL was evaluated according to the revised Scoliosis Research Society 22-item questionnaire (SRS-22r) and stress levels according to the eight-item Bad Sobernheim stress questionnaire (BSSQ-Brace). Independent-sample t-tests were used to compare brace-related QoL and stress level according to participants' sex and brace type. RESULTS: Overall, 32 participants were treated with Boston braces (seven men and 25 women), with a median (IQR) age of 11.00 years (10.00-13.00), and 20 participants were treated with Chêneau braces (three men, 17 women), with a median (IQR) age of 12.50 years (10.00-14.25). The total SRS-22 score was not significantly different between the brace groups (p = 0.158). However, patients in the Boston brace group reported significantly higher satisfaction levels (median = 4.00, IQR = 3.50-4.50) than did those in the Chêneau brace group (median = 3.25, IQR = 2.38-4.13, p = 0.013, moderate effect size = 0.345, 95% CI = 0.060 to 0.590). Furthermore, the BSSQ-brace total score was significantly higher in the Boston brace group (median = 9.00, IQR = 8.00-12.00) than in the Chêneau brace group (median = 7.50, IQR = 4.75-10.00, p = 0.007, moderate effect size = 0.376, 95% CI = 0.130 to 0.590), indicating higher stress levels in the Chêneau brace group. CONCLUSION: The QoL in AIS patients undergoing brace treatment was comparable across groups. Nonetheless, patients who used Chêneau braces experienced higher stress levels and lower treatment satisfaction rates than did those who used Boston braces. These findings can inform clinical decisions regarding prescription of bracing types and highlight the need for further in-depth research.

Prevalence and risk factors of gastro-esophageal reflux disease among college students at a public university in Riyadh, Saudi Arabia.

Background: Gastroesophageal reflux disease (GERD) is one of the most prevalent gastrointestinal disorders worldwide. It manifests when the lower esophageal sphincter malfunctions, causing the stomach's contents to reflux into the esophagus, lead to discomforting symptoms. Heartburn and regurgitation are the typical symptoms of GERD. This study aims to determine the prevalence of GERD and assess its risk factors. Materials and Methods: This cross-sectional study was conducted at IMSIU, Saudi Arabia. An online survey was distributed to the students' email addresses to determine the prevalence of GERD, its related risk factors, and understanding of its symptoms. Results: One thousand five hundred and thirty-three (1533) students participated in the survey. The prevalence of GERD was 34.6%. The majority (79.7%) of the respondent students had heard of GERD. Stress is believed to be a factor in developing GERD by 35.7% of students. Heartburn was the predominant symptom of GERD (76.2%). No association existed between the socio-demographic traits of those with GERD except for age and academic year. Conclusions: It is imperative to raise public awareness of the disorder's characteristics and its modifiable risk factors to prevent the emergence of GERD and its complications.

Evaluating the MDCK cell permeability of greenly synthesize bimetallic Ag/Zn Nanoparticles using leaf extract of Vallaris solanacea as a potential antipesticide-resistant agent.

Bimetallic nanoparticles, particularly Ag/Zn bimetallic nanoparticles, have gained increasing attention due to their unique properties, making them suitable for a variety of applications such as catalysis, water treatment, and environmental remediation. This study aimed to elucidate the use of bimetallic nanoparticles of Ag/Zn as an alternative to resistant pesticides for pest control. Furthermore, this research demonstrates that BNPs can target specific pollutants and degrade them through various mechanisms. BNP docking with the Nilaparvata lugens cytochrome P450 (CYP6ER1) protein exhibited the lowest binding energy of -7.5 kcal/mol. The cell permeability analysis of BNP in plant cells reveals that the BNP has 0 % permeability towards any cell at -10 kcal/mol energy, which is the lowest free energy translocation pathway. The harmful leftover residues of the pesticides have a higher chance of degradability in case of interaction with BNP validated by chemical-chemical interaction analysis. Additionally, MDCK permeability coefficient of small molecules based on the regression model was calculated for BNP which authenticated the efficiency of BNP. Moreover, Swiss ADMET simulated absorption using a boiled egg model with no blood-brain barrier and gastrointestinal crossing for the expected BNP molecule has been observed. Significantly, the findings indicate that employing bimetallic nanoparticles like Ag/Zn is a crucial strategy for bioremediation because they proficiently decompose pesticides while posing no risk to humans. Our results will facilitate the design of novel BNPs materials for environmental remediation and pest control ensuring human health safety that are predicated on bimetallic nanoparticles.

Phytochemicals: a promising approach to control infectious bursal disease.

Infectious bursal disease (IBD) is one of the dangerous diseases of poultry that affects the bursa of Fabricius, which is an important organ of the bird's immune system. IBD virus is resistant to many drugs, making its control difficult. Vaccination of IBD is in practice for a long time worldwide to control IBD, but secondary issues like vaccine failure and lower efficacy lead to their reduced use in the field. Multiple medicines are currently used, but the phytochemicals have emerged as promising agents for controlling IBD. The drugs to be developed should possess direct antiviral properties by targeting viral entry mechanisms, enhancing the host immune response, and inhibiting viral protein synthesis. Phytochemicals have potential to contribute to food security by minimizing the possibility of disease outbreaks and ensuring that consumers worldwide obtain healthy poultry products. It has been now claimed that direct and indirect activities of phytochemicals can be effective in the control of IBDV. Although available evidence suggest that the phytochemicals can contribute in controlling occurrence IBDV, there is a definite need of focused studies to gain more insight and develop rational strategies for their practical use. This review highlights the disease caused by IBDV, inhibition of viral replication, boosting the immune system, disruption of viral membrane, and important phytochemicals showing antiviral activities against IBDV.

The Role of Neoadjuvant Chemotherapy in Patients With Advanced Endometrial Cancer at King Abdulaziz Medical City (KAMC), Saudi Arabia From 2010 to 2022.

BACKGROUND: Endometrial cancer (EC) has multiple modalities of treatment including neoadjuvant chemotherapy (NACT). There is limited research work conducted in Saudi Arabia that shows the benefits of using NACT, followed by interval debulking surgery (IDS) for stages III-IV EC patients. Hence, this study aims to evaluate the effectiveness of using NACT compared to other modalities of treatment in the last 11 years in Saudi Arabia. METHODS: The data of the patients were collected retrospectively between 2010 and 2022 at Princess Noura Oncology Centre, Jeddah, Saudi Arabia. The population was divided based on receiving NACT or taking other modalities for the purpose of assessing the mean survival time in both groups. Best-case and worst-case scenario models were used to illustrate the survival rate of both stages. RESULTS: Forty patients with stages III-IV EC were included and grouped based on the treatment modality. Fourteen (35%) patients were receiving NACT followed by IDS compared with 26 (65%) patients who were using other modalities. In both stages III-IV patients, the mean survival time in the best-case scenario was 49 months in patients treated with NACT, and 82 months in patients who received other modalities. Regarding the worst-case scenario, the average survival time for patients treated with NACT was 22.89 months, which was significantly lower than the average survival time of 56.30 months for patients treated with other therapies. CONCLUSION: In the worst-case scenario, advanced EC patients who underwent NACT had a lower mean survival time than other treatment modalities. However, using NACT is not connected to the outcome in the best-case scenario.

Effects of novel beta-lactam, MC-100093, and ceftriaxone on astrocytic glutamate transporters and neuroinflammatory factors in nucleus accumbens of C57BL/6 mice exposed to escalated doses of morphine.

Chronic exposure to opioids can lead to downregulation of astrocytic glutamate transporter 1 (GLT-1), which regulates the majority of glutamate uptake. Studies from our lab revealed that beta-lactam antibiotic, ceftriaxone, attenuated hydrocodone-induced downregulation of GLT-1 as well as cystine/glutamate antiporter (xCT) expression in central reward brain regions. In this study, we investigated the effects of escalating doses of morphine and tested the efficacy of novel synthetic non-antibiotic drug, MC-100093, and ceftriaxone in attenuating the effects of morphine exposure in the expression of GLT-1, xCT, and neuroinflammatory factors (IL-6 and TGF-ß) in the nucleus accumbens (NAc). This study also investigated the effects of morphine and beta-lactams in locomotor activity, spontaneous alternation percentage (SAP) and number of entries in Y maze since opioids have effects in locomotor sensitization. Mice were exposed to moderate dose of morphine (20 mg/kg, i.p.) on days 1, 3, 5, 7, and a higher dose of morphine (150 mg/kg, i.p.) on day 9, and these mice were then behaviorally tested and euthanized on Day 10. Western blot analysis showed that exposure to morphine downregulated GLT-1 and xCT expression in the NAc, and both MC-100093 and ceftriaxone attenuated these effects. In addition, morphine exposure increased IL-6 mRNA and TGF-ß mRNA expression, and MC-100093 and ceftriaxone attenuated only the effect on IL-6 mRNA expression in the NAc. Furthermore, morphine exposure induced an increase in distance travelled, and MC-100093 and ceftriaxone attenuated this effect. In addition, morphine exposure decreased the SAP and increased the number of arm entries in Y maze, however, neither MC-100093 nor ceftriaxone showed any attenuating effect. Our findings demonstrated for the first time that MC-100093 and ceftriaxone attenuated morphine-induced downregulation of GLT-1 and xCT expression, and morphine-induced increase in neuroinflammatory factor, IL-6, as well as hyperactivity. These findings revealed the beneficial therapeutic effects of MC-100093 and ceftriaxone against the effects of exposure to escalated doses of morphine.

Exploring morphometric transformations in temperature-sensitive NiTi instruments alongside real-time intracanal temperature dynamics.

AIM: This study was twofold: (i) it aimed to investigate the morphometric changes of three temperature-sensitive nickel-titanium (NiTi) instruments at different temperatures, and (ii) to conduct an in vivo real-time analysis of intracanal temperature changes. METHODS: Changes in the shape and length of XP-Endo Shaper, XP-Endo Finisher, and XP-Endo Finisher-R were evaluated in real time whilst heated in a temperature-controlled water bath from 22 to 45°C. Instruments were fixed to a laminated water-resistant 1 mm graph paper attached to a stone block. Instruments were imaged whilst subjected to increasing temperature using a digital camera attached to an operating microscope. From recorded videos, still frames were extracted at 10-s intervals and changes in the length and shape of each instrument were measured and changes were plotted against time. Moreover, the intracanal temperature of distal roots of lower molars was measured in vivo for patients attending the clinic for non-surgical root canal treatments. The temperature was measured using a K-type thermocouple probe inserted into the mid-root level after irrigating the canal with a solution set at room temperature (22°C) or heated to 45°C. The intraoral and intracanal temperatures were recorded using a video camera for 180 s at 5-s intervals to plot the change in the intraoral and intracanal temperature, after both irrigation solution temperatures, with time. RESULTS: The shape transformation of XP-Endo Shaper began at 31.5 ± 2.0°C and reached its optimal transformation at 35.1 ± 1.0°C. For the Finisher and Finisher-R, shape transformations began at 29.2 ± 1.9 and 26.9 ± 2.2°C reaching the optimal transformation at 33.9 ± 1.4 and 32.7 ± 1.7°C, respectively. The average decreases in lengths of XP-Endo Shaper, Finisher, and Finisher-R after full transformation were 0.43 ± 0.23, 1.07 ± 0.22, and 1.15 ± 0.22 mm, respectively. The intracanal temperature reached 32.9 ± 0.8 and 33.2 ± 1.0°C after 3 min of application of irrigation solutions set at 22 or 45°C, respectively. CONCLUSION: The tested instruments exhibited diverse changes in their shapes and lengths at varying temperatures. Despite the temperature of the irrigation solution, the intracanal temperature consistently remained lower than the intracanal temperature once equilibrium was reached. This highlights the importance of considering the temperature of irrigation solution during in vitro testing of endodontic instruments.

Linalool-zinc oxide nanocomposite controls Toxoplasma gondii infection through inhibiting inflammation, oxidative stress, and pathogenicity.

The present in vitro and in vivo study aimed to fabricate and characterize linalool-zinc oxide nanoparticles (Lin-ZNP) and evaluate their effectiveness against Toxoplasma gondii infection in terms of inflammation, oxidative stress, and pathogenicity. Lin-ZNP was synthesized using an ethanolic solution of polyvinyl alcohol. The anti-Toxoplasma and cytotoxicity activities of Lin-ZNP were investigated, along with its effects on nitric oxide (NO) production, caspase-3 activity, and pro-inflammatory genes. After treating T. gondii-infected mice with Lin-ZNP for 14 days, the number and size of tissue cysts, antioxidant potential, pro-inflammatory cytokines, and T. gondii pathogenicity-related genes were evaluated by real-time polymerase chain reaction and Western blot analysis. The Lin-ZNP composite showed a reduced tendency with an average size of 105 nm. Lin-ZNP significantly reduced the viability of tachyzoites. The obtained selectivity index higher than 10, indicating high specificity for parasites with low cytotoxicity to normal cells. The Lin-ZNP significantly (p < 0.05) increased the production of NO, caspase-3 activity, and the expression levels of pro-inflammatory genes. Lin-ZNP significantly (p < 0.001) decreased the size and number of tissue cysts and caused a significant reduction in the level of malondialdehyde and a considerable increase (p < 0.001) in antioxidant enzymes and their expression genes. Lin-ZNP significantly downregulated both mRNA and protein expression of the inflammation-related markers associated with the TLRs/NF-κB pathway. The expression levels of the T. gondii pathogenicity-related genes were significantly downregulated (p < 0.05). The recent survey indicated that Lin-ZNP manages T. gondii infection by its antioxidant activity and inhibiting the TLRs/NF-κB pathway without toxicity in mice.

Statistical design and optimization of nano-transfersomes based chitosan gel for transdermal delivery of cefepime.

OBJECTIVES: This research aimed to overcome challenges posed by cefepime excessive elimination rate and poor patient compliance by developing transdermal delivery system using nano-transfersomes based chitosan gel. METHODS: Rotary evaporation-sonication method and the Box-Behnken model were used to prepare cefepime loaded nano-transfersomes (CPE-NTFs). The physiochemical characterization of CPE-NTFs were analyzed including DLS, deformability index, DSC and antimicrobial study. Optimized CPE-NTFs loaded into chitosan gel and appropriately characterized. In vitro release, ex vivo and in vivo studies were performed. RESULTS: The CPE-NTFs were physically stable with particle size 222.6 ± 1.8 nm, polydispersity index 0.163 ± 0.02, zeta potential -20.8 ± 0.1 mv, entrapment efficiency 81.4 ± 1.1% and deformability index 71 ± 0.2. DSC analysis confirmed successful drug loading and thermal stability. FTIR analysis showed no chemical interaction among the excipients of CPE-NTFs gel. The antibacterial activity demonstrated a remarkable reduction in the minimum inhibitory concentration of cefepime when incorporated into nano-transfersomes. CPE-NTFs based chitosan gel (CPE-NTFs gel) showed significant physicochemical properties. In vitro release studies exhibited sustained release behavior over 24 h, and ex vivo studies indicated enhanced permeation and retention compared to conventional cefepime gel. In vivo skin irritation studies confirmed CPE-NTFs gel was nonirritating and biocompatible for transdermal delivery. CONCLUSION: This research showed nano-transfersomes based chitosan gel is a promising approach for cefepime transdermal delivery and provides sustained release of cefepime.