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Objectives: Autism spectrum disorder (ASD) is a neurological condition that affects social communication and causes repetitive behavior. Autistic children often have comorbidities such as epilepsy. Although the co-occurrence of epilepsy and ASD is frequent, the genetic basis for this association is not fully understood. Many cases of ASD and epilepsy remain unresolved without a molecular diagnosis. The purpose of this study was to determine the molecular diagnostic yield in two Saudi families with a single affected offspring with both ASD and epilepsy using whole-exome sequencing (WES)., Methods: Pediatric patients were diagnosed by a pediatric psychiatrist and neurologist, and diagnosed according to the diagnostic and statistical manual of mental disorders (DSM-V) criteria. WES was used to analyze the coding region of DNA from the two trios. Enrichment analysis was performed on the final list of genes., Results: De novo variations were detected in eleven genes (two in ZBTB17 and FRG, and one each in CAD, CTNNA3, GILGA8J, CCZ1, CASKIN1, growth differentiation factor (GDF7), NBPF10, DUX4L4, and ZNF681). Variations in CTNNA3, GOLGA8J, CASKIN1, CCZ1, and NBPF10 genes were correlated to autism. In addition, similar studies found that CAD, CASKIN1, and GOLGA8J were candidate genes for epilepsy. FRG1 and DUX4 variations were associated with facioscapulohumeral muscular dystrophy. The expression of ZBTB17 and GDF was high in nervous system, and variations in these genes might be correlated to autism and epilepsy., Conclusion: Not all the genes presumed to cause ASD and epilepsy in this study were previously identified, suggesting that more genes were suspected of being involved in ASD and epilepsy co-occurrence., (Copyright: © International Journal of Health Sciences.)

Extreme response of the immune system develops cytokine storm which might be crucial in the pathology of COVID-19. The research aims to evaluate the serum level of IL-6, TNF-α, and IP-10 in severe, mild, and pre-vaccinated one-dose COVID-19 patients and investigate their clinical value and effect in the disease development among different groups of patients. A total of 72 samples were collected 18 as healthy control and 54 from confirmed COVID-19 patients including 18 mild, 18 severe, and 18 pre-vaccinated (one dose). It was confirmed that the severe group of COVID-19 patients had the highest circulating IL-6, TNF- α, and IP-10. IL-6 level in mild and pre-vaccinated (one dose) was significantly lower than in severe. In conclusion, IL-6, TNF-α, and IP-10 are associated with the pathogenicity of COVID-19, furthermore, vaccination could help to control severity of the disease., Competing Interests: Declaration of Competing Interest There are no Ethical or Financial issues, Conflicts of interest, or animal experiments related to this research., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Cancer is a complicated illness that spreads indefinitely owing to epigenetic, genetic, and genomic alterations. Cancer cell multidrug susceptibility represents a severe barrier in cancer therapy. As a result, creating effective therapies requires a better knowledge of the mechanisms driving cancer development, progress, and resistance to medications. The human genome is predominantly made up of long non coding RNAs (lncRNAs), which are currently identified as critical moderators in a variety of biological functions. Recent research has found that changes in lncRNAs are closely related to cancer biology. The vascular endothelial growth factor (VEGF) signalling system is necessary for angiogenesis and vascular growth and has been related to an array of health illnesses, such as cancer. LncRNAs have been identified to alter a variety of cancer-related processes, notably the division of cells, movement, angiogenesis, and treatment sensitivity. Furthermore, lncRNAs may modulate immune suppression and are being investigated as possible indicators for early identification of cancer. Various lncRNAs have been associated with cancer development and advancement, serving as cancer-causing or suppressing genes. Several lncRNAs have been demonstrated through research to impact the VEGF cascade, resulting in changes in angiogenesis and tumor severity. For example, the lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) has been shown to foster the formation of oral squamous cell carcinoma and the epithelial-mesenchymal transition by stimulating the VEGF-A and Notch systems. Plasmacytoma variant translocation 1 (PVT1) promotes angiogenesis in non-small-cell lung cancer by affecting miR-29c and boosting the VEGF cascade. Furthermore, lncRNAs regulate VEGF production and angiogenesis by interacting with multiple downstream signalling networks, including Wnt, p53, and AKT systems. Identifying how lncRNAs engage with the VEGF cascade in cancer gives beneficial insights into tumor biology and possible treatment strategies. Exploring the complicated interaction between lncRNAs and the VEGF pathway certainly paves avenues for novel ways to detect better accurately, prognosis, and cure cancers. Future studies in this area could open avenues toward the creation of innovative cancer therapy regimens that enhance the lives of patients., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Biogenic Zinc oxide (ZnO) nanoparticles (NPs) were synthesized from Celosia argentea ( C. argentea ) plant extract. Structural analysis confirms the successful synthesis of biogenic zinc oxide NPs from C . argentea extract. The biogenic ZnO NPs have an average particle size of 21.55 ± 4.73 nm, a semispherical shape, and a specific surface area of about 50 m 2 /g. The biogenic ZnO NPs have a powerful radical scavenging activity (Ic 50 = 91.24 mg/ml) comparable to ascorbic acid (ASC) as a standard (Ic 50 = 14.37 mg/ml). The antibacterial efficacy was tested against gram-positive and gram-negative bacteria using an agar disc diffusion method. Gram-positive strains with biogenic ZnO NPs have a greater bactericidal impact than gram-negative strains in a concentration-dependent manner. Anticancer activity against Liver hepatocellular cells (HepG2) and Human umbilical vein endothelial cells (HUVEC) was evaluated using a [3-(4,5-dimethylthiazol-2-yl)-2,5diphenyl tetrazolium bromide] (MTT) assay. The results reflect the concentration-dependent cytotoxic effect of biogenic ZnO NPs against HepG2 cells even at low concentrations (Ic 50 = 49.45 μg/ml) compared with doxorubicin (Ic 50 = 14.67 μg/ml) and C. argentea extract (Ic 50 = 112.24 μg/ml). The cell cycle and gene expression were analyzed to determine the potential anticancer mechanism. The flow cytometric analysis of the cell cycle revealed that biogenic ZnO NPs induce oxidative stress that activates the apoptotic genes NF-κB, CY-C, and P53, leading to cell death. The Celosia argentea improved the antioxidant, antibacterial, and anticancer activities of ZnO NPs without altering their structural properties. The effect of green synthesis on the bioactivity of biogenic ZnO NPs in vivo is recommended for future work., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Alghamdi, Al-Zahrani, Altarjami, Al Abdulmonem, Samir, Said, Shami, Mohamed and Ezzeldien.)

SARS-CoV-2, which initiated the worldwide COVID-19 epidemic in 2019, has rapidly emerged and spread, resulting in significant public health challenges worldwide. The COVID-19 severity signs and their association with specific genes have been investigated to better comprehend this phenomenon. In this study, several genes were investigated to see whether they correspond with COVID-19 sickness severity. This research aims to determine and evaluate certain gene expression levels associated with the immune system, as these genes were reported to play important roles in immune control during the COVID-19 outbreak. We analyzed two immunity-linked genes: CD27 and SAMHD1 in COVID-19 patients' samples using RT-PCR, compared them to the samples from recovered, immunized, and healthy individuals. These data were examined to determine the potential relationships between clinical patterns, illness severity, and progression, and SARS-CoV-2 infection immunology. We observed that CD27 gene expression was higher in COVID-19 vaccinated and control groups, but lower in active and recovered COVID-19 patients. On the other hand, SAMHD1 gene expression was elevated in infected and recovered COVID-19 groups. According to our study, the proteins CD27 and SAMHD1 are essential for controlling the immunological response to COVID-19. Changes in their expression levels could increase the susceptibility of patients to severe complications associated with the disease. Therefore, the gene expression level of these proteins could serve as viable prognostic markers for COVID-19., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

Background/objective/methods: Glutathione-S-transferase Mu1 ( GSTM1 ) and glutathione peroxidase 1 ( GPX1 ) are known antioxidant enzymes that help protect cells from the oxidative damage that occurs from smoking. This study explored the correlation between GSTM1 and GPX1 levels between a group of smokers with the GSTM1 and GPX1 genes in the Saudi population and a control group and investigated the genetic risk factors in the group of smokers., Results: The control and smokers' group ( n = 50; aged 22.3 ± 3.1 years; BMI 24.6 ± 5.9 kg/m 2 ) were genotyped using quantitative polymerase chain reaction (qPCR). In comparison with the control group, the smokers' group displayed a different genotype disruption of GSTM1 and GPX1 . Carriers of the homozygous (TT) genotype of GSTM1 had more than a twofold (OR = 2.71, 95% CI = 0.10-70.79, P = 1.000) smoking risk than the carriers of the heterozygous (CT) genotype. Those with the GPX1 gene showed no risk in the control and smokers' groups. Smokers with the TT/GG combination (homozygous for GPX1 and normal for GPX1 ) were identified as high risk (OR = 2.58, 95% CI = 0.096-69.341)., Conclusion: The main outcomes showed no significant association between genetic polymorphism of the GSTM1 and GPX1 genes and cigarette smoking in the Saudi Arabian population. However, the results showed a slight decrease in the number of GSTM1 and GPX1 gene modifications among smokers., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Journal of Pharmacy and Bioallied Sciences.)

Breast cancer (BC) is one of the most widespread types of cancer affecting females, and therefore, early diagnosis is critical. BC is a complex heterogeneous disease affected by several key pathways. Among these, WNT proteins and their frizzled receptors (FZD) have been demonstrated to be crucial in regulating a number of cellular and molecular events in BC tumorigenesis. The role of the WNT receptor, FZD8, in BC has received minimal attention; for that reason, the present study examined the prognostic value of its protein expression pattern in a BC cohort. FZD8 cytoplasmic expression pattern analysis revealed that ~38% of the primary samples presented with a high expression profile, whereas ~63% of the samples had a low expression profile. Overall, ~46% of the malignant tissues in the lymph node-positive samples exhibited an increased FZD8 cytoplasmic expression, whereas 54% exhibited low expression levels. An increased expression of FZD8 was associated with several clinicopathological characteristics of the patients, including a low survival rate, tumor vascular invasion, tumor size and grade, and molecular subtypes. Affymetrix microarray triple-negative BC datasets were analyzed and compared with healthy breast tissues in order to predict the potential interfering microRNAs (miRNAs) in the WNT/FZD8 signaling pathway. A total of 29 miRNAs with the potential to interact with the WNT/FZD8 signaling pathway were identified, eight of which exhibited a significant prediction score. The target genes for each predicted miRNA were identified. On the whole, the findings of the present study suggest that FZD8 is a potential prognostic marker for BC, shedding some light onto the silencing mechanisms involved in the complex BC signaling., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Al-Zahrani et al.)

The claudin multigene family is associated with various aberrant physiological and cellular signaling pathways. However, the association of claudins with survival prognosis, signaling pathways, and diagnostic efficacy in colon cancer remains poorly understood. Methods: Through the effective utilization of various bioinformatics methods, including differential gene expression analysis, gene set enrichment analysis protein-protein interaction (PPI) network analysis, survival analysis, single sample gene set enrichment analysis (ssGSEA), mutational variance analysis, and identifying receiver operating characteristic curve of claudins in The Cancer Genome Atlas colon adenocarcinoma (COAD). Results: We found that: CLDN2, CLDN1, CLDN14, CLDN16, CLDN18, CLDN9, CLDN12, and CLDN6 are elevated in COAD. In contrast, the CLDN8, CLDN23, CLDN5, CLDN11, CLDN7, and CLDN15 are downregulated in COAD. By analyzing the public datasets GSE15781 and GSE50760 from NCBI-GEO (https://www.ncbi.nlm.nih.gov/geo/), we have confirmed that CLDN1, CLDN2, and CLDN14 are significantly upregulated and CLDN8 and CLDN23 are significantly downregulated in normal colon, colon adenocarcinoma tumor, and liver metastasis of colon adenocarcinoma tissues from human samples. Various claudins are mutated and found to be associated with diagnostic efficacy in COAD. Conclusion: The claudin gene family is associated with prognosis, immune regulation, signaling pathway regulations, and diagnosis of COAD. These findings may provide new molecular insight into claudins in the treatment of colon cancer., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Alghamdi and Al-Zahrani.)

Introduction: Foodborne trichothecene T-2 Toxin, is a highly toxic metabolite produced by Fusarium species contaminating animal and human food, causing multiple organ failure and health hazards. T-2 toxins induce hepatotoxicity via oxidative stress causing hepatocytes cytotoxicity and genotoxicity. In this study, curcumin and taurine were investigated and compared as antioxidants against T-2-provoked hepatotoxicity. Methods: Wistar rats were administrated T-2 toxin sublethal oral dose (0.1 mg/kg) for 2 months, followed by curcumin (80 mg/kg) and taurine (50 mg/kg) for 3 weeks. Biochemical assessment of liver enzymes, lipid profiles, thiobarbituric acid reactive substances (TBARs), AFU, TNF-α, total glutathione, molecular docking, histological and immunohistochemical markers for anti-transforming growth factor-β1 (TGFβ1), double-strand DNA damage (H2AX), regeneration (KI67) and apoptosis (Active caspase3) were done. Results and Discussion: Compared to T-2 toxin, curcumin and taurine treatment significantly ameliorated hepatoxicity as; hemoglobin, hematocrit and glutathione, hepatic glycogen, and KI-67 immune-reactive hepatocytes were significantly increased. Although, liver enzymes, inflammation, fibrosis, TGFβ1 immunoexpressing and H2AX and active caspase 3 positive hepatocytes were significantly decreased. Noteworthy, curcumin's therapeutic effect was superior to taurine by histomorphometry parameters. Furthermore, molecular docking of the structural influence of curcumin and taurine on the DNA sequence showed curcumin's higher binding affinity than taurine. Conclusion: Both curcumin and taurine ameliorated T-2 induced hepatotoxicity as strong antioxidative agents with more effectiveness for curcumin., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Al-Zahrani, Balgoon, El-Sawi, Alshubaily, Jambi, Khojah, Baljoon, Alkhattabi, Baz, Alharbi, Ahmed, Abo elkhair, Ismael and Gebril.)

Background: Lung Squamous Cell Carcinoma (LUSC) is a major subtype of lung malignancies and is associated with the cause of cancer-mediated mortality worldwide. However, identification of transcriptomic signatures associated with survival-prognosis and immunity of tumor remains lacking., Method: The GSE2088, GSE6044, GSE19188, GSE21933, GSE33479, GSE33532, and GSE74706 were integrated for identifying differentially expressed genes (DEGs) with combined effect sizes. Also, the TCGA LUSC cohort was used for further analysis. A series of bioinformatics methods were utilized for conducting the whole study., Results: The 831 genes (such as DSG3, PKP1, DSC3, TPX2, and UBE2C ) were found upregulated and the 731 genes (such as ABCA8, SELENBP1, FAM107A, and CACNA2D2 ) were downregulated in the LUSC. The functional enrichment analysis identifies the upregulated KEGG pathways, including cell cycle, DNA replication, base excision repair, proteasome, mismatch repair, and cellular senescence. Also, the key hub genes (such as EGFR, HRAS, JUN, CDH1, BRCA1, CASP3, RHOA, HDAC1, HIF1A, and CCNA2 ) were identified along with the eight gene modules that were significantly related to the protein-protein interaction (PPI) . The clinical analyses identified that the overexpression group of CDH3, PLAU, PKP3, STIL, CALU, LOXL2, POSTN, DPP3, GALNT2, LOX, and ITPA are substantially associated with a poor survival prognosis and the downregulated group of IL18R1 showed a similar trend. Moreover, our investigation demonstrated that the survival-associated genes were correlated with the stromal and immune scores in LUSC, indicating that the survival-associated genes regulate tumor immunity. The survival-associated genes were genetically altered in 27% of LUSC patients and showed excellent diagnostic efficiency. Finally, the consistent expression level of CDH3, PLAU, PKP3, STIL, CALU, LOXL2, POSTN, DPP3, GALNT2, and ITPA were found in the TCGA LUSC cohort., Conclusions: The identification of key transcriptomic signatures can be elucidated by the crucial mechanism of LUSC carcinogenesis., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

Background: By the end of 2019, the COVID-19 pandemic spread all around the world with a wide spectrum of clinical presentations ranging from mild to moderate to severe or critical cases. T cell subtype dysregulation is mostly involved in the immunopathogenic mechanism. The present study aimed to highlight the role of monitoring T cell subtypes and their activation (expression of CD38) in COVID-19 patients compared to healthy subjects and their role in predicting severity and patients' outcomes., Materials: The study involved 70 adult COVID-19 confirmed cases stratified into three groups: a mild/asymptomatic group, a clinically moderate group, and a clinically severe/critical group. Flow cytometry analysis was used for the assessment of CD3 + cells for total T cell count, CD4 + cells for helper T cells (Th), CD8 + cells for cytotoxic T cells (Tc), CD4 + CD25 + cells for regulatory T cells (T reg), and CD38 expression in CD4 + T cells and CD8 + T cells for T cell activation., Results: A statistically significant difference was found between COVID-19 cases and healthy controls as regards low counts of all the targeted T cell subtypes, with the lowest counts detected among patients of the severe/critical group. Furthermore, CD38 overexpression was observed in both CD4 + and CD8 + T cells., Conclusion: Decreased T cell count, specifically CD8 + T cell (Tc), with T cell overactivation which was indicated by CD38 overexpression on CD4 + and CD8 + T cells had a substantial prognostic role in predicting severity and mortality among COVID-19 patients. These findings can provide a preliminary tool for clinicians to identify high-risk patients requiring vigilant monitoring, customized supportive therapy, or ICU admission. Studies on larger patient groups are needed.

Background: Chronic stress can hinder wound healing as it suppresses both the cellular and innate immune responses. Objectives: The study aims to assess the effectiveness of the administration of topical and oral Cucurbita pepo L. (CP) ethanolic extract in prompting excisional wound healing in rats exposed to chronic stress, and to explain how it works. Materials and methods: Fifty albino rats assigned to five groups (n = 10) were utilized in this study. The chronic unpredictable mild stress (CUMS) model was used for 4 weeks to induce depressive-like behavior in rats, and a forced swim test and corticosterone were assessed to confirm its occurrence. During the experiment, an excisional wound was induced in the rats and followed. Oxidant/antioxidants status and pro-inflammatory cytokines levels were measured in the serum and wound area. Gene expression of pro-inflammatory cytokines was also assessed using RT-PCR. Wound closure histopathological changes and immunohistochemical expression of CD68, CD3, and CD4 at the wound area was assessed. Results: The administration of CP, both orally and topically, significantly reduced (p < 0.001) the depressive-like behavior and corticosterone and pro-inflammatory cytokines levels, while it significantly up-regulated the antioxidant activity compared to the untreated and topically CP-treated groups. Both topically CP-treated and combined CP-treated groups showed complete re-epithelialization, reduced inflammatory cells infiltration, collagen fibers deposition, and significantly increased CD3, CD4 positive T cells count, with a superior effect in the combined CP-treated groups. Conclusion: Cucurbita pepo L., administrated both topically and orally, can enhance the wound healing process in rats with depressive-like behavior mostly through the antioxidant, anti-inflammatory, and antidepressant activities observed in this study.

Aptamers, the nucleic acid analogs of antibodies, bind to their target molecules with remarkable specificity and sensitivity, making them promising diagnostic and therapeutic tools. The systematic evolution of ligands by exponential enrichment (SELEX) is time-consuming and expensive. However, regardless of those issues, it is the most used in vitro method for selecting aptamers. Therefore, recent studies have used computational approaches to reduce the time and cost associated with the synthesis and selection of aptamers. In an effort to present the potential of computational techniques in aptamer selection, a simple sequence-based method was used to design a 69-nucleotide long aptamer (mod&#95;09) with a relatively stable structure (with a minimum free energy of -32.2 kcal/mol) and investigate its binding properties to the tyrosine kinase domain of the NT-3 growth factor receptor, for the first time, by employing computational modeling and docking tools.

The study aimed to determine the interaction of using LS and CA in combination on liver, kidney, and heart functions in rats and to evaluate the role of antioxidant effects of LS against CA-induced hepato-renal toxicity. This study was conducted on 36 male rats divided into four groups (n = 9). The groups were; the control, LS-treated (10 g/100 g of food), CA-treated (5 g/100 g of food), and combined LS plus CA-treated groups for 6 weeks. Kidney, liver and heart functions as well as oxidant/antioxidant profile were biochemically assessed in the serum using ELISA. The impact of LS and CA on kidney and liver was histopathologically assessed. Rats fed on diet supplemented with LS for 6 weeks showed no significant change in serum levels of the biochemical markers of liver, kidney and heart functions, while supplementation with CA significant increased (p < 0.001) the serum levels of these markers compared to the control group. Combined administration of LS and CA significantly reduced the serum levels of these parameters compared to CA-treated group. Oxidative markers significantly increased while the antioxidants one decreased in CA-treated group compared to the control. Combined LS and CA significantly improve the oxidant/antioxidant profile as well as histopathological impact compared to CA-treated group., (© 2022. Pleiades Publishing, Ltd.)

Wnt signalling receptors, Frizzleds (FZDs), play a pivotal role in many cellular events during embryonic development and cancer. Female breast cancer (BC) is currently the worldwide leading incident cancer type that cause 1 in 6 cancer-related death. FZD receptors expression in cancer was shown to be associated with tumour development and patient outcomes including recurrence and survival. FZD6 received little attention for its role in BC and hence we analysed its expression pattern in a Saudi BC cohort to assess its prognostic potential and unravel the impacted signalling pathway. Paraffin blocks from approximately 405 randomly selected BC patients aged between 25 and 70 years old were processed for tissue microarray using an automated tissue arrayer and then subjected to FZD6 immunohistochemistry staining using the Ventana platform. Besides, Ingenuity Pathway Analysis (IPA) knowledgebase was used to decipher the upstream and downstream regulators of FZD6 in BC. TargetScan and miRabel target-prediction databases were used to identify the potential microRNA to regulate FZD6 expression in BC. Results showed that 60% of the BC samples had a low expression pattern while 40% showed a higher expression level. FZD6 expression analysis showed a significant correlation with tumour invasion ( p < 0.05), and borderline significance with tumour grade ( p = 0.07 ). FZD6 expression showed a highly significant association with the BC patients' survival outcomes. This was mainly due to the overall patients' cohort where tumours with FZD6 elevated expression showed higher recurrence rates (DFS, p < 0.0001, log-rank) and shorter survival times (DSS, p < 0.02, log-rank). Interestingly, the FZD6 prognostic value was more potent in younger BC patients as compared to those with late onset of the disease. TargetScan microRNA target-prediction analysis and validated by miRabel showed that FZD6 is a potential target for a considerable number of microRNAs expressed in BC. The current study demonstrates a potential prognostic role of FZD6 expression in young BC female patients and provides a better understanding of the involved molecular silencing machinery of the Wnt/FZD6 signalling. Our results should provide a better understanding of FZD6 role in BC by adding more knowledge that should help in BC prevention and theranostics., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Assidi, Buhmeida, Al-Zahrani, Al-Maghrabi, Rasool, Naseer, Alkhatabi, Alrefaei, Zari, Elkhatib, Abuzenadah, Pushparaj and Abu-Elmagd.)

Inflammatory lung disorders (ILDs) are one of the world's major reasons for fatalities and sickness, impacting millions of individuals of all ages and constituting a severe and pervasive health hazard. Asthma, lung cancer, bronchiectasis, pulmonary fibrosis acute respiratory distress syndrome, and COPD all include inflammation as a significant component. Microbe invasions, as well as the damage and even death of host cells, can cause and sustain inflammation. To counteract the negative consequences of irritants, the airways are equipped with cellular and host defense immunological systems that block the cellular entrance of these irritants or eliminate them from airway regions by triggering the immune system. Failure to activate the host defense system will trigger chronic inflammatory cataracts, leading to permanent lung damage. This damage makes the lungs more susceptible to various respiratory diseases. There are certain restrictions of the available therapy for lung illnesses. Vitamins are nutritional molecules that are required for optimal health but are not produced by the human body. Cholecalciferol (Vitamin D) is classified as a vitamin, although it is a hormone. Vitamin D is thought to perform a function in bone and calcium homeostasis. Recent research has found that vitamin D can perform a variety of cellular processes, including cellular proliferation; differentiation; wound repair; healing; and regulatory systems, such as the immune response, immunological, and inflammation. The actions of vitamin D on inflammatory cells are dissected in this review, as well as their clinical significance in respiratory illnesses.

Ovarian cancer (OC) is the deadliest among all gynecological cancers. Epidemiological studies showed that obesity might influence many cancers including OC. One of the key factors that may link obesity and OC is leptin (LEP), known as an adipokine with pleiotropic effects on body homeostasis. This study aims to investigate the expression pattern of LEP, assess the methylation profiles of LEP and their associations with clinicopathological features including survival outcomes of OC patients. The protein expression of LEP was evaluated in 208 samples using both tissue microarray and immunohistochemistry techniques. The methylation profiles of LEP were measured in 63 formalin-fixed, paraffin-embedded tumor tissues by quantitative polymerase chain reaction using a MethyLight assay. Our results showed a significant association of LEP protein overexpression with several clinicopathological variables, mainly tumor subtype, LVI, age of menarche, tumor size and stage ( p < 0.04). Kaplan-Meier analysis (using low expression versus high expression as a discriminator) indicated that LEP protein overexpression is a powerful positive prognosticator of both OC recurrence (DFS) and disease-specific survival (DSS) in our OC cohort (log-rank p = 0.01 and p = 0.002, respectively). This implies that patients with high LEP expression profiles live longer with less recurrence rates. Methylation analysis results demonstrated a clear association between no/low LEP protein expression pattern (38%) and LEP promoter CpG island hypermethylation (43%). Results of this study suggest that LEP is a powerful prognosticator of OC recurrence and DSS. LEP expression in OC seems to be regulated by its promoter hypermethylation through gene partial/total silencing. Further multi-institutional studies using larger cohorts are required to demystify the intricate molecular functions of this leptin-driven effects in OC pathophysiology and to accurately assess its theranostic potential and validate its prognostic/predictive power in OC onset, progression towards more effective and personalized management of OC patients.

Among all gynecological cancers, ovarian cancer (OC) is one of the deadliest types of cancer worldwide. Epigenetic silencing of some genes has been reported to be associated with OC. In this context, Klotho (KL) gene methylation is a promising biomarker for OC. The present study aimed to investigate the methylation profiles of KL and assess its prognostic value. A total of 63 formalin-fixed paraffin-embedded tissue samples from patients with primary OC were collected and analyzed in the present study. The methylation profiles of KL were assessed by performing DNA bisulfate treatment followed by DNA promoter methylation analysis using the MethyLight assay. The results revealed KL promoter hypermethylation in 62% of the OC cohort. Additionally, significant associations were observed between KL methylation profiles and tumor subtype (P<0.0001) and tumor site (P=0.039). Furthermore, Kaplan-Meier analysis revealed that a worse disease-specific survival was significantly associated with hypermethylated KL (P=0.03, log-rank; hazard ration, 0.58; 95% confidence interval (CI), 0.26-0.90). Cox regression multivariate analysis indicated that KL promoter methylation was an independent OC prognostic indicator (P=0.029). The current study suggested that KL may be a novel biomarker to predict prognosis in patients with OC, since patients with higher KL promoter methylation were more likely to have a poor prognosis and would therefore require frequent follow-up and integrative personalized therapeutic approaches., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Al-Zahrani et al.)

Apolipoprotein B100 (ApoB100) is a glycoprotein and a member of the adipokine family. It plays a central role in lipoprotein metabolism. Many research studies have revealed a strong relation between ApoB100 and metabolic syndrome (MetS) and insulin resistance. In our research, we examined the relationship between ApoB100 rs693 gene polymorphism, body mass index (BMI) and the probability of MetS in young female students studying at King Abdulaziz University (KAU) in Saudi Arabia. The study group comprised 141 females whose ages ranged from 18 to 25 years. Anthropometric measurements and biochemical parameters were measured alongside a genetic analysis of ApoB100 rs693. The BMI, glucose concentration and total cholesterol level were found to be significantly associated with the ApoB100 rs693 gene. The differences noted between control and MetS groups regarding glucose concentrations were statistically significant ( P  = 0.001). A growing number of young females are being diagnosed with MetS in KAU because of unhealthy eating habits, in combination with the absence of physical exercise, causing increased body weight and the potential progression of chronic diseases. Our study showed that the allele associated with hypertensive individuals at ApoB100 rs693 and MetS may have a direct genetic influence. Further research on expanded sample sizes, however, is required in order to draw rigid conclusions., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Authors.)

Background: Depression and contact dermatitis (CD) are considered relatively common health problems that are linked with psychological stress. The antioxidant, anti-inflammatory, and antidepressant activities of pumpkin were previously reported. Objectives: This study aimed to evaluate the efficacy of the combined topical and oral application of pumpkin fruit ( Cucurbita pepo L.) extract (PE) in relieving CD associated with chronic stress-induced depression and compare it to the topical pumpkin extract alone and to the standard treatment. Materials and Methods: Forty male albino rats were exposed to chronic unpredictable mild stress (CUMS) for 4 weeks for induction of depression and then exposed to (1-fluoro-2, 4-dinitrofluorobenzene, DNFB) for 2 weeks for induction of CD. Those rats were assigned into 4 groups ( n = 10 each); untreated, betamethasone-treated, PE-treated and pumpkin extract cream, and oral-treated groups. Treatments were continued for 2 weeks. All groups were compared to the negative control group ( n = 10). Depression was behaviorally and biochemically confirmed. Serum and mRNA levels of pro-inflammatory cytokines, such as TNF-α, IL-6, COX-2, and iNOS, were assessed. Oxidant/antioxidant profile was assessed in the serum and skin. Histopathological and immunohistochemical assessments of affected skin samples were performed. Results: Pumpkin extract, used in this study, included a large amount of oleic acid (about 56%). The combined topical and oral administration of PE significantly reduced inflammatory and oxidative changes induced by CD and depression compared to the CD standard treatment and to the topical PE alone. PE significantly alleviated CD signs and the histopathological score ( p < 0.001) mostly through the downregulation of pro-inflammatory cytokines and the upregulation of antioxidants. Conclusion: Pumpkin extract, applied topically and orally, could be an alternative and/or complementary approach for treating contact dermatitis associated with depression. Further studies on volunteer patients of contact dermatitis are recommended., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Balgoon, Al-Zahrani, Jaouni and Ayuob.)

Cancer cells are altered with cell cycle genes or they are mutated, leading to a high rate of proliferation compared to normal cells. Alteration in these genes leads to mitosis dysregulation and becomes the basis of tumor progression and resistance to many drugs. The drugs which act on the cell cycle fail to arrest the process, making cancer cell non-responsive to apoptosis or cell death. Vinca alkaloids and taxanes fall in this category and are referred to as antimitotic agents. Microtubule proteins play an important role in mitosis during cell division as a target site for vinca alkaloids and taxanes. These proteins are dynamic in nature and are composed of α-β-tubulin heterodimers. β-tubulin specially βΙΙΙ isotype is generally altered in expression within cancerous cells. Initially, these drugs were very effective in the treatment of cancer but failed to show their desired action after initial chemotherapy. The present review highlights some of the important targets and their mechanism of resistance offered by cancer cells with new promising drugs from natural sources that can lead to the development of a new approach to chemotherapy., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Nano-biopolymers could be employed for the delivery of active compounds to increase their stability, bioavailability, efficacy and sustainability. The bioactive chitosan polymer (Cts) was extracted from grown fungus, Cunninghamella elegans, and used for loading ceftriaxone (CFT) and forming the nano-conjugates using tripolyphosphate (TPP) - ionic crosslinking method. The characterization of synthesized CFT/chitosan nanoparticles (NCT) revealed that they chemically crosslinked and had particles' size mean of 56 nm. The CFT loading capacity onto NCT was 54.37%, while its entrapment efficiency was apparently high (79.43%); the maximum released of CFT was 78% from NCT composite after 90 h from dialysis. The CFT/NCT antibacterial activity was confirmed against 3 strains of Staphylococcus aureus (methicillin resistants), using disc diffusion and scanning images of electron microscope, which elucidate that CFT/NCT nano-composite had a vigorous action toward bacterial cells; most cells were ruptured and exploded after 6 h of exposure and entirely lysed after 9 h. The formulation of CFT/NCT nano-composite is exceedingly recommended for enhancing drug biocidal activity, especially against resistant bacterial strains., (Copyright © 2019. Published by Elsevier B.V.)

Objective: To examine the association between increased body mass index (BMI) values and the risk of metabolic syndrome (MetS) in young female science students., Methodology: The study population was 174 female students aged 18-25 years attending King Abdulaziz University (KAU) in the Kingdom of Saudi Arabia (KSA). Anthropometric measurements obtained included weight, height, waist, and hips circumferences. Blood pressure was also measured, and blood samples were collected for measurements of total cholesterol, triglyceride (TG), high-density lipoprotein (HDL), fasting blood glucose (FBG), and other biochemical parameters., Results: Around 17.7% of the students were at risk of developing MetS, with three or more risk factors detected, and 45% of the students had one or two risk factors. Increased BMI values were associated with an elevated risk of developing MetS, as 41.4% of the overweight students and 44.8% of the obese students had three or more risk factors., Conclusion: The prevalence of MetS is increasing in Young female university in the KSA as a result of an unhealthy lifestyle, including a lack of physical activity, leading to increased weight and the possible development of chronic diseases., (Copyright © 2019 Diabetes India. Published by Elsevier Ltd. All rights reserved.)

Naturally occurring polyamines like Putrescine, Spermidine, and Spermine are polycations which bind to the DNA, hence stabilizing it and promoting the essential cellular processes. Many synthetic polyamine analogues have been synthesized in the past few years, which have shown cytotoxic effects on different tumours. In the present study, we evaluated the antiproliferative effect of a novel, acylspermidine derivative, (N-(4-aminobutyl)-N-(3-aminopropyl)-8-hydroxy-dodecanamide) (AAHD) on HepG2 cells. Fluorescence staining was performed with nuclear stain (Hoechst 33342) and acridine orange/ethidium bromide double staining. Dose and the time-dependent antiproliferative effect were observed by WST-1 assays, and radical scavenging activity was measured by ROS. Morphological changes such as cell shrinkage & blebbing were analyzed by fluorescent microscopy. It was found that AAHD markedly suppressed the growth of HepG2 cells in a dose- and time-dependent manner. It was also noted that the modulation of ROS levels confirmed the radical scavenging activity. In the near future, AAHD can be a promising drug candidate in chalking out a neoplastic strategy to control the proliferation of tumour cells. This study indicated that AAHD induced anti-proliferative and pro-apoptotic activities on HCC. Since AAHD was active at micromolar concentrations without any adverse effects on the healthy cells (Fibroblasts), it is worthy of further clinical investigations., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: Since 2004, the Kingdom of Saudi Arabia has pursued a policy of malaria elimination. The distribution of malaria at this time was constrained to regions located in the South Western part of the country. The present study aimed to understand the risk of malaria infection and factors associated with these events between March 2006 and August 2007 in one part of Aseer region., Methods: The study was carried out in Tihama Qahtan area in the far southeastern part of Aseer, historically the most malaria endemic area of this region. The area covers 54 villages served by three primary health care centres (Wadi Alhayah, Alfarsha and Albuqaa). Malaria cases were detected using passive case detection (PCD) at the three health centres for 18 months from March 2006, each positive case was investigated using patient and household level enquiries. In addition, four cross-sectional surveys in 12 villages were undertaken using rapid diagnostic tests within the catchments of each health centre coinciding with malaria transmission seasons., Results: Among 1840 individuals examined in the PCD survey, 49 (2.7%) were positive for malaria, most were Plasmodium falciparum cases and one was a P. vivax case. The majority of these infections were likely to have been acquired outside of the area and represent imported cases, including those from the neighboring region of Jazan. Among the 18 locally acquired cases, the majority were adult males who slept outdoors. 3623 individuals were screened during the cross-sectional surveys, 16 (0.44%) were positive and infections only detected during peak, potential transmission periods., Conclusion: There was evidence of local malaria transmission in the Tihama Qahtan area in 2006-2007, however prevalence and incidence of new infections was very low, making the future ambitions of elimination biologically feasible. The constant source of imported infections must be considered in the area's elimination ambitions, alongside strong behavioural community messages about sleeping outdoors unprotected and travel to malaria endemic areas outside the region.

Malaria at international borders presents particular challenges with regards to elimination. International borders share common malaria ecologies, yet neighboring countries are often at different stages of the control-to-elimination pathway. Herein, we present a case study on malaria, and its control, at the border between Saudi Arabia and Yemen. Malaria program activity reports, case data, and ancillary information have been assembled from national health information systems, archives, and other related sources. Information was analyzed as a semi-quantitative time series, between 2000 and 2017, to provide a plausibility framework to understand the possible contributions of factors related to control activities, conflict, economic development, migration, and climate. The malaria recession in the Yemeni border regions of Saudi Arabia is a likely consequence of multiple, coincidental factors, including scaled elimination activities, cross-border vector control, periods of low rainfall, and economic development. The temporal alignment of many of these factors suggests that economic development may have changed the receptivity to the extent that it mitigated against surges in vulnerability posed by imported malaria from its endemic neighbor Yemen. In many border areas of the world, malaria is likely to be sustained through a complex congruence of factors, including poverty, conflict, and migration.

Background: In 2004, a revised action plan was developed, supported by the World Health Organization, to eliminate malaria from Saudi Arabia by preventing re-introduction of malaria into regions since declared malaria free, eliminating foci of transmission in the Mecca and Medina areas and a concerted effort of foci surveillance and control, to eliminate malaria from the regions of Jazan and Aseer. This paper provides the context, activities, progress, and possible contributions toward malaria elimination in the Aseer region since 2000, with a more detailed analysis of the spatial location of locally acquired case incidence since 2012., Methods: This is a descriptive study of all available Ministry of Health surveillance data and process reports since 2000, with higher spatial resolution analysis of data between 2012 and 2015., Results: In 2000, there were 511 cases of Plasmodium falciparum locally acquired infection. The following 4 years witnessed a dramatic decline in cases to only 18 locally acquired infections reported in 2005. A resurgence in local infections was reported in 2006 (93) and 2007 (165), thereafter (2008-2014) local cases continued to decline to fewer than 40 per year across the region. However, in 2015, a small rise was noted (51). All locally acquired infections were P. falciparum. There has been a constant flow of imported infections into Aseer since 2000, mostly among immigrant labour from Pakistan, India, Sudan, and Yemen. Imported infections have included both Plasmodium vivax and P. falciparum. The spatial extent of malaria appears to be changing, but there remain two intractable areas Sarat Abeda and Dhran Aljanub, where risks per reporting centre have changed little since 2001, remaining above 0.5 per 10,000 population. Only seven villages contributed 55% of all locally acquired infection since 2012., Discussion: Aseer has reached a state of very low incidence of locally acquired infections, despite a constant source of imported infections from outside the country. How many of the local infections are F2 generations from imported infections or how many are a result of residual active transmission between asymptomatic carriers of infections transmitted by pockets of existing Anopheles arabiensis populations remains unknown. A more detailed investigation of the spatial and temporal patterns of infected hosts, parasites and vectors would help define whether this region has managed to effectively prevent local transmission of new infections.

Background: The sandfly Phlebotomus papatasi is the vector of Leishmania major, the main causative agent of Old World cutaneous leishmaniasis (CL) in Saudi Arabia. Sandflies inject saliva while feeding and the salivary protein PpSP32 was previously shown to be a biomarker for bite exposure. Here we used recombinant PpSP32 to evaluate human exposure to Ph. papatasi bites, and study the association between antibody response to saliva and CL in endemic areas in Saudi Arabia., Methodology/principal Findings: In this observational study, anti-PpSP32 antibodies, as indicators of exposure to sandfly bites, were measured in sera from healthy individuals and patients from endemic regions in Saudi Arabia with active and cured CL. Ph. papatasi was identified as the primary CL vector in the study area. Anti-PpSP32 antibody levels were significantly higher in CL patients presenting active infections from all geographical regions compared to CL cured and healthy individuals. Furthermore, higher anti-PpSP32 antibody levels correlated with the prevalence and type of CL lesions (nodular vs. papular) observed in patients, especially non-local construction workers., Conclusions: Our findings suggest a possible correlation between the type of immunity generated by the exposure to sandfly bites and disease outcome.

In the Kingdom of Saudi Arabia (KSA), Old World cutaneous leishmaniasis (CL) is mainly caused by Leishmania major and Leishmania tropica parasites. Diagnosis of CL is predominately made by clinicians, who at times fail to detect the disease and are unable to identify parasite species. Here, we report the development of a chemiluminescent enzyme-linked immunosorbent assay (CL-ELISA) to measure the levels of anti-α-galactosyl antibodies in human sera. Using this assay, we have found that individuals infected with either Leishmania spp. had significantly elevated levels (up to 9-fold higher) of anti-α-Gal IgG compared to healthy control individuals. The assay sensitivity was 96% for L. major (95% CI; 94-98%) and 91% for L. tropica (95% CI; 86-98%) infections and therefore equivalent to restriction fragment length polymorphism-polymerase chain reaction analysis of parasite ITS1 gene. In addition, the assay had higher sensitivity than microscopy analysis, which only detected 68 and 45% of the L. major and L. tropica infections, respectively. Interestingly, up to 2 years following confirmed CL cure individuals had 28-fold higher levels of anti-α-Gal IgG compared to healthy volunteers. Monitoring levels of anti-α-Gal antibodies can be exploited as both a diagnostic tool and as a biomarker of cure of Old World CL in disease elimination settings.

Significant headway has been made in the global fight against malaria in the past decade and as more countries enter the elimination phase, attention is now focused on identifying effective strategies to shrink the malaria map. Saudi Arabia experienced an outbreak of malaria in 1998, but is now on the brink of malaria elimination, with just 82 autochthonous cases reported in 2012. A review of published and grey literature was performed to identify the control strategies that have contributed to this achievement. The number of autochthonous malaria cases in Saudi Arabia decreased by 99.8% between 1998 and 2012. The initial steep decline in malaria cases coincided with a rapid scaling up of vector control measures. Incidence continued to be reported at low levels (between 0.01 and 0.1 per 1,000 of the population) until the adoption of artesunate plus sulfadoxine-pyrimethamine as first line treatment and the establishment of a regional partnership for a malaria-free Arabian Peninsula, both of which occurred in 2007. Since 2007, incidence has decreased by nearly an order of magnitude. Malaria incidence is now very low, but a high proportion of imported cases, continued potential for autochthonous transmission, and an increased proportion of cases attributable to Plasmodium vivax all present challenges to Saudi Arabia as they work toward elimination by 2015.

Objective: To determine the outcome of infants born to diabetic mothers at Security Forces Hospital, Riyadh, Saudi Arabia, and compare the complications seen in these infants with infants of non-diabetic mothers., Methods: This is a concurrent prospective cohort study of a population of newborn infants delivered at Security Forces Hospital, Riyadh, Saudi Arabia for diabetic mothers between January 2011 and November 2011., Results: A total of 601 infants were enrolled in the study consisting of 319 infants of non-diabetic mothers, and 282 infants of diabetic mothers. Infants of diabetic mothers showed significantly higher rates of associated complications and prolonged hospital stay reflected in their admission to the neonatal intensive care when compared with infants of non-diabetic mothers. There was no difference in rate of complications between infants of gestational diabetics and pre-gestational diabetics., Conclusion: Our study showed that diabetic pregnancies are associated with an increased incidence of neonatal complications. These seem to be related to the degree of maternal glycemic control. The higher rates of complications among our infants of diabetic mothers, particularly major congenital malformations call for those involved in the care of diabetic mothers to consolidate their efforts to facilitate early booking in specialist clinics.

The transmission of malaria across the Arabian Peninsula is governed by the diversity of dominant vectors and extreme aridity. It is likely that where malaria transmission was historically possible it was intense and led to a high disease burden. Here, we review the speed of elimination, approaches taken, define the shrinking map of risk since 1960 and discuss the threats posed to a malaria-free Arabian Peninsula using the archive material, case data and published works. From as early as the 1940s, attempts were made to eliminate malaria on the peninsula but were met with varying degrees of success through to the 1970s; however, these did result in a shrinking of the margins of malaria transmission across the peninsula. Epidemics in the 1990s galvanised national malaria control programmes to reinvigorate control efforts. Before the launch of the recent global ambition for malaria eradication, countries on the Arabian Peninsula launched a collaborative malaria-free initiative in 2005. This initiative led a further shrinking of the malaria risk map and today locally acquired clinical cases of malaria are reported only in Saudi Arabia and Yemen, with the latter contributing to over 98% of the clinical burden., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

In order to evaluate the contribution of polymorphisms of the adiponectin gene, ADIPOQ, to the risk of colon cancer, we conducted a case-control study of 60 colon cancer patients and 60 age, gender and ethnicity-matched controls in the Saudi population. We tested the hypothesis by analyzing the genotypes for two single nucleotide polymorphisms (SNPs), rs1501299 (G276T) and rs2241766 (T45G), in the ADIPOQ gene. In addition, the study was also designed to assess whether the two SNPs contribute to circulating adiponectin levels. We observed an increased risk of colon cancer associated with the 276T allele. The odds ratio (OR) was 2.64 [95% confidence interval (CI), 0.49-14.6]. The G allele at the T45G polymorphism was associated with a lower risk of colon cancer (OR=0.41; 95% CI, 0.19-0.86). Our results suggest that the risk of developing colon cancer may be partially explained by genetic polymorphisms in the ADIPOQ gene.