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BACKGROUND: Road Traffic Injuries (RTIs) is a vital concern that affect mutually both developed and undeveloped countries. In Saudi Arabia the death rate from traffic accidents is approximately 28.8 per 100,000 people. In the year 2018, the Kingdom of Saudi Arabia finally set an end to its legal ban on car driving for women, providing the way for millions of new drivers to steer across the country. Conversely, gender has a statistically momentous impact on driving behavior. AIM: In this study we studied about the principal attitudes and behaviors of female drivers in Capital City Riyadh. METHODS: This is a cross-sectional study in which we analyzed female’s behavior which they are living in Riyadh City using the “Dulla index” instrument to identify whether aggressive driving behavior is expected in females in Riyadh. RESULTS: Using DDDI, we found that aggressive and dangerous driving behavior is not common among female drivers in Riyadh City. However, aggressive behavior was found three times more among employees when they drive than students, as well as participants with the educational level of (diploma/bachelor), (Singles/Divorced/widows), and those who (employees) were more likely associated with the behaviors of risky driving than their counterpart. CONCLUSION: This study revealed that the women who reside in Riyadh city are well-educated about the traffic laws, and the rate of aggressive, dangerous driving behavior was uncommon among them. Further studies are required to augment knowledge and condense the hazardous driving behaviors in Saudi Arabia.

The innate immune system is the main and first line of defense mechanism present in the human body, which acts against a foreign antigen. To function it utilize several mechanisms, among those are the primary one is recognizing the foreign antigen which is accomplished via decidedly complicated group of molecules termed as pattern recognition receptors (PRRs), which perceive various diverse structures present on the pathogen known as pathogen-associated molecular patterns (PAMPs). PRPs include several classes of receptors’, functions, and nature of these receptors vary from each other depending upon the molecular composition of PAMPs they detect. However, the Toll-like receptors (TLRs) are among the class of PRPs, which are studied widely. In this review, we have presented the contemporary understanding of pathogens recognition by various receptor classes including PRRs. In addition, we also discuss PRPs associated signaling pathways associated with antimicrobial immune response triggering.

Objectives: Osteoporosis is the most prevalent metabolic bone disorder worldwide. This review was undertaken to compare the efficacies of bisphosphonates therapies for patient persistence and compliance for the treatment of osteoporosis. Methods: A systematic review was performed in accordance with the available reporting items. MEDLINE and Cochrane library databases were applied for literature searched up to January 2020. All major studies such as prospective, retrospective and review articles that examined patient persistence or compliance to bisphosphonates for osteoporosis were included. Results: The literature search found 656 relevant published reports, out of which 87 were included. The 10, 712, 176 osteoporotic patients were studied for patient persistence and 5, 875, 718 patients were studied for patient compliances. Analysis of all studied bisphosphonates showed almost similar patterns for patient persistence rates as it was decreased over the time following initial prescription, but persistence length was found to be significantly higher for alendronate therapy as compared to the other studied bisphosphonates (p0.05). Analysis of patient compliances with etidronate therapy showed the highest percent medication possession ratio (MRP) at 12 months, followed by the MRPs of ibandronate, alendronate, risedronate, and clodronate. Conclusions: This is the first systematic review that shows the comparison of the efficiencies of bisphosphonates for patient persistence and compliance for the treatment of osteoporosis. The data showed that the length of patient persistence was highest for alendronate therapy, whereas patient compliance was highest for etidronate therapy for the treatment of osteoporosis.

BACKGROUND: The coronavirus disease 2019 (COVID-19) is a global public health disaster and knowledge of its associated risk factors provides protection/slowdown against its transmission. AIM: This study was undertaken to investigate all major risk factors associated with transmission of the COVID-19 infection. METHODS: The data on the risk associated factors for the COVID-19 transmission were collected from the Texas Medical Association, Center for Disease Prevention and Control, World Health Organization, and Health and Safety Executive. The collected data were combined, analyzed, and presented as percentage mean ± SD. RESULTS: The collective data showed that among games such as playing football and basketball are highly risky followed by swimming in public pool and playing at the beach. Whereas, playing golf and tennis are not risky (p < 0.05). Moreover, the carryout food from the restaurants is much safer as compared with eating at buffet, in restaurants (p < 0.01). The data on social gathering showed that religious places, sports stadium, music concert, cinema halls, amusement parks, attending funerals, and wedding showed a higher risk of spreading COVID-19. The data on general outing showed that going to gymnasium, traveling by bus or plane, and visiting in salon are highly risky (p < 0.01) for COVID-19 infection. Moreover, hugging, shaking hands, and kissing are also highly risky for the COVID-19 infection. CONCLUSIONS: This study provides the collective information on the risk factors associated with the COVID-19 transmission. The findings can contribute to the concerned authorities to formulate the preventive measures to limit spread of the COVID-19 infection.

Objective: This study was undertaken to elaborate the precautionary methods taken by the College of Medicine of Qassim University for conduction of students’ academic examinations (exams) in the university campus during the COVID-19 pandemic. Methods: This study was conducted on undergraduate medical students (n=674) from the September 2020 to April 2021 in the College of Medicine at Qassim University. The switch into conducting exams within the center was managed by the exam committee. Multiple online workshops were conducted to the staff and students regarding the precautionary measures and the exam procedures in order to prevent the transmission of the disease among students and staff. New guidelines for undertaking the exams were designed and implemented at the exam centers in the university campus during COVID-19 pandemic. Results: All the exams were conducted in a satisfactory manner under one roof under the supervision of the invigilation team within the examination center located in the university campus. The strict implementation of precautionary guidelines and the crucial steps to prevent the spread of Coronavirus facilitated the accomplishment of this vital task in a smooth manner with no case of COVID-19 reported in any of the staff or students who participated in this activity. Conclusions: This study revealed the precautionary methods and steps undertaken by the college of medicine, Qassim University in terms of conducting exams within campus. We concluded that if implementation of precautionary measures should be carried out in a proper manner then it is possible to conduct exams under one roof.

One of the leading causes of death worldwide is cancer. Excessive production of tumor necrosis factor (TNF)-α is known to activate nuclear transcription factor (NF)-κB, which plays a lethal role in the onset of multiple disorders including cancer. In this study, we aimed to determine the therapeutic role of novel gold nanoparticles conjugated with citrate (AuNPs-CIT) on the elevated expression of TNF-α in breast cancer cells. AuNPs-CIT were synthesized by the citrate-reduction method and were characterized by UV-VIS spectroscopic analysis, zeta-potential analysis, and size analysis. The potential of these newly generated AuNPs-CIT particles was tested on phorbol 12-myristate 13-acetate (PMA)-stimulated cancer cells. Our data showed that the AuNPs-CIT were spherical, with a mean size of 21.3±0.65 nm and a stabilized zetapotential at −41.4±0.98 mV. These newly generated AuNPs-CIT nanoparticles inhibited PMA-induced activation and nuclear translocation of NF-κB p65 in MCF-7 cells. They also have the tendency to block TNF-α expression in stimulated cancer cells. In conclusion, AuNPs-CIT inhibits PMA-induced TNF-α mRNA and protein expression via deactivation of NF-κB signaling in breast cancer cells. These findings suggest that AuNPs-CIT might be useful in cancer treatment.

Mucormycosis (MCM) is a rare fungal disorder that has recently been increased in parallel with novel COVID-19 infection. MCM with COVID-19 is extremely lethal, particularly in immunocompromised individuals. The collection of available scientific information helps in the management of this co-infection, but still, the main question on COVID-19, whether it is occasional, participatory, concurrent, or coincidental needs to be addressed. Several case reports of these co-infections have been explained as causal associations, but the direct contribution in immunocompromised individuals remains to be explored completely. This review aims to provide an update that serves as a guide for the diagnosis and treatment of MCM patients’ co-infection with COVID-19. The initial report has suggested that COVID-19 patients might be susceptible to developing invasive fungal infections by different species, including MCM as a co-infection. In spite of this, co-infection has been explored only in severe cases with common triangles: diabetes, diabetes ketoacidosis, and corticosteroids. Pathogenic mechanisms in the aggressiveness of MCM infection involves the reduction of phagocytic activity, attainable quantities of ferritin attributed with transferrin in diabetic ketoacidosis, and fungal heme oxygenase, which enhances iron absorption for its metabolism. Therefore, severe COVID-19 cases are associated with increased risk factors of invasive fungal co-infections. In addition, COVID-19 infection leads to reduction in cluster of differentiation, especially CD4+ and CD8+ T cell counts, which may be highly implicated in fungal co-infections. Thus, the progress in MCM management is dependent on a different strategy, including reduction or stopping of implicit predisposing factors, early intake of active antifungal drugs at appropriate doses, and complete elimination via surgical debridement of infected tissues.

This study examined an association of ATP2B1 gene polymorphism and hypertension in the Saudi population. The 246 hypertensive cases and 300 healthy human controls were genotyped. The results showed that genotypes rs.207075 (CA + AA) [p = 0.05; OR: 95% CI, 1.5:(1.0 to 2.4) and p = 0.001, OR: 95% CI, 2.4: (1.5 to 4.0) and rs2681472 (CT + TT) [p = 0.05; OR: 95% CI, 1.5 (1.0 to 2.4) and p = 0.006 OR: 95% CI, 2.0 (1.2 to 3.1) respectively] associated with the risk of hypertension. Cases carrying the recessive models: [(CA + AA)/(CT + TT)] and [(AA)/(TT)] genotypes confer a strong susceptibility risk of hypertension [p = 0.002; OR: (95%CI) 1.8 (1.2 to 2.6) and p = 0.001; OR: (95%CI) 2.6 (1.5 to 4.7) respectively]. However, cases with body-mass-index (BMI)

Streptomyces is a genus with known biocontrol activity, producing a broad range of biologically active substances. Our goal was to isolate local Streptomyces species, evaluate their capacity to biocontrol the selected phytopathogens, and promote the plant growth via siderophore and indole acetic acid (IAA) production and phosphate solubilization. Eleven isolates were obtained from local soil samples in Saudi Arabia via the standard serial dilution method and identified morphologically by scanning electron microscope (SEM) and 16S rRNA amplicon sequencing. The biocontrol of phytopathogens was screened against known soil-borne fungi and bacteria. Plant growth promotion capacity was evaluated based on siderophore and IAA production and phosphate solubilization capacity. From eleven isolates obtained, one showed 99.77% homology with the type strain Streptomyces tricolor AS 4.1867, and was designated S. tricolor strain HM10. It showed aerial hyphae in SEM, growth inhibition of ten known phytopathogens in in vitro experiments, and the production of plant growth promoting compounds such as siderophores, IAA, and phosphate solubilization capacity. S. tricolor strain HM10 exhibited high antagonism against the fungi tested (i.e., Colletotrichum gloeosporides with an inhibition zone exceeding 18 mm), whereas the lowest antagonistic effect was against Alternaria solani (an inhibition zone equal to 8 mm). Furthermore, the most efficient siderophore production was recorded to strain HM8, followed by strain HM10 with 64 and 22.56 h/c (halo zone area/colony area), respectively. Concerning IAA production, Streptomyces strain HM10 was the most effective producer with a value of 273.02 μg/ml. An autochthonous strain S. tricolor HM10 should be an important biological agent to control phytopathogens and promote plant growth.

Backgroundː Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), within few months of being declared as a global pandemic by WHO, the number of confirmed cases has been over 75 million and over 1.6 million deaths since the start of the Pandemic and still counting, there is no consensus on factors that predict COVID-19 case progression despite the diversity of studies that reported sporadic laboratory predictive values predicting severe progression. We review different biomarkers to systematically analyzed these values to evaluate whether are they are correlated with the severity of COVID-19 disease and so their ability to be a predictor for progression. Methods The current meta-analysis was carried out to identify relevant articles using eight different databases regarding the values of biomarkers and risk factors of significance that predict progression of mild or moderate cases into severe and critical cases. We defined the eligibility criteria using a PICO model. Results Twenty-two relevant articles were selected for meta-analysis the following biomarkers C-reactive protein, interleukin-6, LDH, neutrophil, %PD-1 expression, D-dimer, creatinine, AST and Cortisol all recorded high cut-off values linked to severe and critical cases while low lymphocyte count, and low Albumin level were recorded. Also, we meta- analyzed age and comorbidities as a risk factors of progression as hypertension, Diabetes and chronic obstructive lung diseases which significantly correlated with cases progression (p Conclusions ː The current meta-analysis is the first step for analysing and getting cut-off references values of significance for prediction COVID-19 case progression. More studies are needed on patients infected with SARS-CoV-2 and on a larger scale to establish clearer threshold values that predict progression from mild to severe cases. In addition, more biomarkers testing also help in building a scoring system for the prediction and guiding for proper timely treatment.

Background The nuclear factor kappa-B (NF-κB) is a major transcription factor responsible for the production of numerous inflammatory mediators, including the tumor necrosis factor (TNFα), which has a lethal association with cancer's onset. The silver nanoparticles (AgNPs) are widely used in cancer treatment and several other biomedical applications. Objective The study aimed to determine the effects of silver citrate nanoparticles (AgNPs-CIT) on NF-κB activation together with TNFα mRNA/protein expressions in the phorbol myristate acetate (PMA)-stimulated MCF-7 human breast cancer cell-lines. Methods The AgNPs-CIT were synthesized by the reduction method, and the prepared AgNPs-CIT were characterized for their shape, absorption in UV-VIS electromagnetic radiations, size distribution, ζ-potential, and antioxidant activity. The MCF-7 cell-lines were pretreated with AgNPs-CIT and stimulated with PMA. The TNFα mRNA expressions were determined by real-time PCR, whereas the protein production was determined by the ELISA. The NF-κB activity was distinctly observed by highly-specific DNA-based ELISA, and by NF-κB-specific inhibitor, Bay 11-7082. Results The prepared AgNPs-CIT were spherical and have an absorption wavelength range of 381-452 nm wherein the particles size ranged between 19.2±0.1 to 220.77±0.12 nm with the charge range -9.99±0.8 to -34.63±0.1 mV. The prepared AgNPs-CIT showed comparative antioxidant activity at >40% inhibitions level of the DPPH radicals. The AgNPs-CIT were found to be non-toxic to MCF-7 cell-lines and inhibited PMA-induced activation of the NF-κBp65, and also the mRNA/protein expression of TNFα. Conclusion This is the first report that showed AgNPs-CIT inhibited TNFα expression via deactivation of the NF-κB signaling event in stimulated breast cancer cells. The results have important implications for the development of novel therapeutic strategies for the prevention/treatment of cancers and/or inflammatory disorders.

Lung cancer is a leading cause of cancer-associated death in all over the globe. This study was undertaken to determine the expression and interaction of membrane-bound receptors CD74 and CD44 in human lung adenocarcinoma cells and their associated signaling was also attempted. Levels of CD74 and CD44 were studied in human lung adenocarcinoma-evolved cells A549 and H460. CD74-mediated downstream signaling was studied by the nuclear-transcription-factor NF-κB and prostaglandin E (PGE) production. Flow-cytometric analysis showed that both CD74 and CD44 were perfectly expressed in A549 cells. Importantly, Western immunoblotting showed that A549 cells expressed only two isoforms of CD74 at 33 and 35 kDa but isoform at 41 kDa was absent. These results were verified in H460 cells. Confocal microscopy showed CD74 and CD44 was colocalized but heterotypic interaction between them was missing in both A549 and H460 cells. Activation of NF-κB and production of PGE in human lung cancer cells were comparable with other cancer cells. In conclusion, this is the first study that shows A549 and H460 cells expressed two distinctive isoforms of CD74 but isoform at 41 kDa was absent. Due to the absence of this isoform, the direct physical interaction between them CD74 and CD44 was lacking. Furthermore, the data also demonstrated that lacking of direct physical interaction between CD74 and CD44 had no effect on NF-κB activation and PGE production indicating that CD74-mediated downstream signaling occurs either through coreceptors or indirect interaction with CD44 in human lung cancer cells. Abbreviation: CD: cluster of differentiation; SCLC: small cell lung cancer; NSCLC: nonsmall cell lung cancer; SCC: squamous cell carcinoma; ADC: adenocarcinoma; LCC: large cell carcinoma.

Background: Screening of blood products is considered a mandatory protocol implemented in health care facilities in order to reduce the onset of transfusion-transmitted infections (TTIs). This study was aimed to determine the sero-prevalence of ABO and Rh blood groups and their associated TTIs among blood donors in the Central Region of Saudi Arabia. Methods: This was retrospective study performed on the blood donors’ records from March 2017 to December 2018 at Buraidah Central Hospital Blood Bank. Study was conducted on a total of 4590 blood donors. ABO and Rh typing was performed.The blood samples were also screened serologically for hepatitis B surface antigen (HBsAg), anti-hepatitis B core total antibodies (anti-HBc total), hepatitis C virus (HCV), human immunodeficiency viruses (HIV), human T-lymphotrophic virus-1 (HTLV-1) and veneral disease research laboratory test(VDRL) for syphilis. Results: Out of 4590 blood donors, O positive blood group was found to be highest (42%), followed by A positive (23.4%), B positive (20.9%), O negative (5.45%), AB positive (3.4%), A negative (2.8%), B negative (2.1%) and AB negative (0.5%). Moreover, total number of Rh-negative donors was significantly lowered as compared with Rh-positive. Seroreactive tests were found to be positive in only 1.002% of all studied donors and mainly found in male donors. Among TTI, anti-HBc total was the highest (0.784%), followed by HBsAg, HCV, VDRL and TPHA. Whereas all tested donors were found to be negative for HIV infections. Conclusions: The information collected for the frequency of ABO blood phenotypic groups has a vital significance in establishing a simple blood group database. This study clearly determined significantly lower rate of seropositive TTIs among the studied blood donors but still steps are needed to improve the knowledge and to prevent the seropositive occurrence of TTIs. Keywords: Blood group, TTIs, Anti-HBc total, HBsAg, HCV, VDRL, KSA

One of the leading causes of death worldwide is cancer. Excessive production of tumor necrosis factor (TNF)

Microphthalmia-associated transcription factor (MITF) is a master regulatory factor for melanocytes. MITF regulates multiple pigmentary genes for maintaining cellular homeostasis. MicroRNAs (miRNAs) play crucial roles in numerous biological processes however their molecular/cellular mechanisms to regulate pigmentation have not been fully explored. This study was undertaken to investigate the role of miRNAs in skin depigmentation via regulation of MITF gene. Depigmentation in C57BL/6 black mice was induced by an autoimmune response against tyrosinase. Bioinformatics approach was used to detect miRNAs conserved in 3'untraslated region (3'UTR) of MITF mRNA. The iMC23 mouse melanocytes were used for transfection experiments. The data demonstrated that the MITF mRNA/protein was markedly low in lesional skin of depigmented mice (p 0.05). Targetscan genomic database determined that 3'UTR of mouse MITF constitutes 4819 nucleotide bases and has 23 conserved sites for different miRNAs To validate the pairing of these predicted miRNAs with MITF mRNA, five miRNAs were deregulated in lesional skin (p 0.05). Among them, mmu-miR-181a-5p and mmu-miR-183-5p were up-regulated, whereas mmu-miR-26a-5p, mmu-miR-26b-5p and mmu-miR-32-5p were down-regulated (p 0.05). To verify these results, the iMC23 mouse melanocytes were used. Transfection of iMC23 cells with specific miRNAs mimics or inhibitors or with 3'UTR reporter clone of MITF, showed only mmu-miR-183-5p binds to 3'UTR of MITF mRNA and regulates its expression in iMC23 melanocytes. In conclusions, this is the first study shows that miR-183-5p is a direct regulator of MITF in iMC23 melanocytes. Thus, miR-183-5p is an important regulator of melanocytes homeostasis and may be a novel target for autoimmune depigmentation therapy.

This study demonstrated the association of polymorphisms in

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is RNA virus, responsible for coronavirus disease 2019 (COVID-19), which has now taken the form of a pandemic. Even though the world has undertaking all possible measures to impede the spread of this droplet infection, still the prevalence of COVID-19 is on the rise and has infected more than 208 countries all over the globe. Reviewing the website and global articles from PubMed, Scopus and other cites on COVID-19 a global pandemic, this review article provides an update on the all major aspects of coronavirus such as origin, epidemiology, mode of transmission, structure and molecular characterization, characterization of spike protein, clinical features including cutaneous manifestation, radiological features, molecular testing, histopathology and the current preventive approaches. Importantly, review also provides an update on current projections of Saudi Arabia on COVID-19 pandemic.

Anti-DNA antibodies are now considered as a universal diagnostic feature for the patients with systemic lupus erythematosus (SLE) but the mechanism(s) involved in the generation of these autoantibodies remains to be investigated. Bisphenol A (BPA) is a synthetic phenol extensively used in the manufacturing of polycarbonated plastics. Upon mixing in the diet, it causes several health hazards. This study was undertaken to investigate the contribution of BPA induced DNA damage in SLE patients. Human DNA was modified by BPA in-vitro and the binding characteristics of SLE circulating immunoglobulin Gs (SLE-IgGs) with BPA damaged DNA (BPA-DNA) were screened and compared with the IgGs from normal healthy humans (NH-IgGs). Immunogenicity of BPA-DNA was determined by immunisation in rabbits. DNA from SLE patients (SLE-DNA) or healthy humans (NH-DNA) were isolated and their binding specificity with rabbit anti-BPA-DNA-IgGs was studied. Treatment of human DNA with BPA caused extensive damaged. Circulating SLE-IgGs showed strong recognition of BPA-DNA. BPA-DNA induced high titre antibodies in rabbits. Rabbit anti-BPA-DNA-IgGs showed strong cross reaction with isolated DNA from SLE patients. In short, we concluded that the structural alterations in DNA by BPA, generate neo-epitopes that may be a factor responsible for the induction of anti-DNA autoantibodies in SLE.

Honey has been used as a traditional remedy for various health benefits. This study investigated the potential of honey against the onset of autoimmune diabetes and its associated secondary complications in type 1 diabetic (T1D) experimental animals. Autoimmune diabetes was induced in Sprague Dawley rats, and at the same time, the rats were treated with honey or metformin. Sandwich ELISAs were used to estimate blood glucose, hemoglobin A1C (HbA1c), total cholesterol, and triglycerides. Histopathological examinations determined the T1D-induced lesions on kidneys, pancreas, cornea, and retina. Treatment of rats with honey during the course of T1D induction showed a significant reduction in fasting-blood-glucose and HbA1c (p < 0.01), and total lipid profile was also improved (p < 0.05). Not only these, but honey also reduced the T1D-induced lesions in the kidney, pancreas, and cornea/retina (p < 0.05). Metformin showed similar effects and was used as a positive control. In conclusion, honey showed therapeutic potential against the onset of autoimmune diabetes, as it reduces blood glucose/HbA1c and improves the lipid profile by reducing the plasma levels of total cholesterol, low-density lipoproteins (LDL), very low-density lipoprotein (VLDL), and triglycerides. Moreover, it also showed protective potential against the development of diabetic nephropathy, pancreatitis, and retinopathy.

Hydroxyl radicals (OH.) are one of the most active reactive oxidants recognized for their deleterious effects to cause protein oxidative damage. Thymoquinone, a monoterpene molecule abundantly present in black cumin and known for its pharmacological activities, but its activity against the OH.-induced protein oxidative damage has never been explored. This study determined the therapeutic potential of thymoquinone against OH.-induced oxidative human hemoglobin damage. Novel data demonstrated that thymoquinone provides structural protection of hemoglobin against oxidative damage. Treatment of hemoglobin with OH. induces hypochromicity at 280 and 405 nm, whereas thymoquinone reversed these hypochromic effects. In addition, OH. cause significant reduction in tryptophan fluorescence, however thymoquinone also reversed these damaging effects. Thymoquinone also reduces OH.-induced hydrophobicity and also reduces OH.-induced carbonylation. Moreover, it also inhibits thermal stabilization of OH.-hemoglobin complex. SDS-PAGE of unmodified hemoglobin showed four bands, which disappeared upon OH. treatment and these changes were also retained by thymoquinone. In conclusion, this is the first study that shows the therapeutic potential of thymoquinone against OH.-induced oxidative damage in human hemoglobin.

Background: Medical services at trauma centers regularly encounter severe burn patients but prehospital care of these patients in Saudi Arabia is comparatively unexplored. This study evaluates the knowledge and experience of physicians working in trauma centers of Qassim province of Saudi Arabia for the management of patients with burn injuries. Methods: This is a cross sectional study performed on 204 physicians working in the trauma centers of Qassim province. Physicians’ knowledge and experience were assessed via administration of validated questionnaires and the data were analyzed using SPSS software. Results: Among total studied physicians, only 35.3% and 24.0% gave the right answer to the question on the diagnosis of burn skin in depth/extent for adults and pediatric patients, respectively. Importantly, 93.6% physicians responded correctly for first aid treatment. For the parkland concept, 62.2% responded correctly, however, only 22.5% understand the colloid fluid concept. The 74% physicians knew the methods of fluid revival for mass burn injuries and about half of studied physicians showed right knowledge for intubation for breathing for mass burn injuries. Only 47.5% physicians understand the concept of electrolyte disorder. Conclusions: This is the first study from the central region of Saudi Arabia that analyzed the knowledge and experience of physicians working in trauma centers for the management of patients with burn injuries. Overall data showed that ~60% physicians working in trauma centers have knowledge for handling the patients with burn injuries but the rest needed counseling, therefore proper training sessions for them are needed for management of burn patients.

This study investigated the atopic march on the basis of genetics. This research detected 227 variants in the filaggrin gene (FLG gene). Missense, silent, non-sense, frame-shift and non-coding mutations were detected in exon 3 of the FLG gene in patients with bronchial asthma, atopic dermatitis, allergic rhinitis and mixed atopy. Missense mutation was detected at c.8343 G > C (p. Asp2781Glu) in all adult asthmatic and allergic rhinitis patients. Whereas, mutation at c.8360 C > T/A (p. Arg2787 His/Leu) was detected in all childhood asthmatic and mixed atopic patients. A non-coding mutation was detected at c.12365 in atopic dermatitis and bronchial asthma patients. Furthermore, DNA sequencing of asthmatic and mixed atopic patients showed missense mutations at c.6073 C > T (p. Gly2025Glu) and a silent mutation at c. 8341 G > A (p. Asp2781Asp).

Regulation of melanogenesis by tyrosinase has now become an attractive approach for treatment of vitiligo but still the role of tyrosinase in the induction of depigmentation remains largely unexplored. This study was explored the role of tyrosinase in the induction of autoimmune depigmentation in C57BL/6 mice. Depigmentation was induced in C57BL/6 mice by tyrosinase immunization. Induced depigmentation was characterized by visual detection and was verified by histopathological analysis of lesional and non-lesinal skin biopsies. Moreover, induced depigmentation was re-validated by gene expression analysis of vitiligo-relevant genes by Taqman assays. Immunization of C57BL/6 mice by tyrosinase induces depigmentation on hairs as well as on skin. Immunoassays with Protein A-purified immune IgGs showed high titre antibodies against tyrosinase. Histopathological analysis showed that the total melanocytes were depleted from the basal layer of the epidermis and also from the dermis of depigmented lesions. The gene expression of vitiligo-relevant genes TYRP1, DCT, MLANA, MCIR, POMC, FOXJ2, CSNK1G3, SOX10, PMEL and KIT was significantly low in lesional skin as compared with non-lesional skin (

Background: Myoglobin is an oxygen binding protein and its dysfunction has been associated with the pathology of several human disorders. This study was undertaken to investigation the role of hydrogen peroxide (H2O2) in the formation of met-myoglobin and the protective potential of four different reductants such as uric acid, folic acid, glutathione and ascorbic acid were also tested against met-myoglobin formation. Methods: Human myoglobin was treated with H2O2 in-vitro in order to prepare met-myoglobin. The generation of met-myoglobin was confirmed by UV-visible spectroscopy and its stability was analysed by the treatment of human myoglobin with H2O2 at varying pH or time. High performance liquid chromatography (HPLC) was used to determine the oxidatively modified heme products in met-myoglobin. Spectroscopic analysis was used to identify the protective potential of uric acid, folic acid, glutathione and ascorbic acid against the formation of met-myoglobin. Results: The novel data of this study showed that H2O2 induced extensive damage of myoglobin but the treatment with uric acid, folic acid, glutathione or ascorbic acid provides protection of myoglobin against H2O2 induced oxidative damaged. The study apparently proved the protective potential of all these compounds against the toxicity produced by H2O2. Conclusion: This is the first study that shows uric acid, folic acid, glutathione and ascorbic acid provide protection against the generation of toxic met-myoglobin and might be used therapeutically to modify the blood conditions in order to prevent the progression of human disorders associated with myoglobin dysfunction.

Background Cutaneous leishmaniasis (CL) is well linked with immunogenetic factors. This study was undertaken to test the association of TNF-α − 308 and IFN-γ + 874 gene polymorphisms with the susceptibility of Leishmania (L) species among CL patients in central region of Saudi Arabia. Methods This is a case-control study involved 169 Saudi subjects with different L. species and 199 healthy controls from central region of Saudi Arabia. All subjects were characterized by TNF-α − 308 G/A and IFN-γ + 874 A/T gene polymorphisms using PCR. Results Evaluation of genotyping and allelic frequency of TNF-α − 308 G/A in different L. species showed no significant association compared to controls (p > 0.05). Except, in cases of L. tropica that showed significantly higher TNF-α − 308 A versus G allele frequency (p = 0.0004). Evaluation of genotyping of IFN-γ + 874 (TT versus AA+AT recessive) and allelic frequency of IFN-γ + 874 (T versus A) showed significant higher in L. major and also in total CL cases as compared to healthy controls (p L. major, L. tropica or total CL cases with synergistically combined high TNF-α 308/INF-γ 874 alleles. Conclusions This is the first report that shows the gene polymorphisms of TNF-α − 308 G/A and IFN-γ + 874 A/T in Saudi patients with different L. species infections. Data showed that the TNF-α-308 G/A gene polymorphism is not associated with the susceptibility of CL in Saudi subjects. The only correlation was found in between A versus G allelic frequency in L. tropica. Importantly, IFN-γ + 874 A/T polymorphism was found to be associated with the susceptibility of L. major and also with total CL subjects. Moreover, data from synergistically combined high TNF-α 308/INF-γ 874 alleles strongly suggest their potential role in the susceptibility of leishmania infection.

Bronchial asthma (BA), atopic dermatitis (AD), and allergic rhinitis (AR) are well known atopic disorders with complex etiologies. This study was undertaken to investigate the role of filaggrin, eosinophil major basic protein (MBP) and leukotriene B4 (LTB4) in patients with BA, AD, and AR. Sera from 1,246 patients with different atopic disorders and 410 normal healthy controls were collected and were evaluated for filaggrin, MBP and LTB4 by specific sandwich ELISAs, whereas immunoglobulin E (IgE) was used as a positive control for atopic patients. Serum analysis showed that filaggrin levels were remarkably high in patients with AD and in patients with multiple (mixed) atopic disorders (p < 0.001), whereas its levels in BA and AR patients were low but much higher than in normal human sera (p < 0.01). MBP levels were also high in AR, BA and mixed atopic patients, whereas AD patients showed no increase of MBP (p > 0.05). In contrast, LTB4 level was found to be significantly low in all tested atopic patients groups as compared to the levels of LTB4 present in normal human sera (p < 0.001). In conclusion, these findings support an association between filaggrin, MBP or LTB4 and atopic disorders. Our data strongly suggest that filaggrin, MBP or LTB4 might be useful in elucidating the mechanisms involved in the pathogenesis of these atopic disorders.

Objectives Honey total polyphenolic fraction (HTPF) is reported to have anti-disease potential, however the role of HTPF in the regulation of microRNAs (miRNAs) has never been investigated. This study was undertaken to investigate the potential of HTPF against inflammation via regulation of miRNAs in pancreatic islets of Langerhans. Methods Pancreatic islets were isolated from C57BL/6 mice and HTPF was purified from honey. Bioinformatics algorithms were used to determine miRNA target genes. Expression of miRNA and mRNA was determined using their specific taqman assays. Pairing between miRNA and 3′ untranslated region (3′UTR) of mRNA was confirmed using luciferase reporter clone containing the 3′UTR of mRNA sequences and results were verified by transfection of mouse pancreatic β-cell line Min6 with miRNA inhibitors. Results The data showed that mmu-miR-26a-5p is a direct regulator of cyclooxygenase-2 (COX-2) expression and HTPF inhibits COX-2 expression or prostaglandin E2 (PGE2) production via up-regulating mmu-miR-26a-5p expression. Transfection of islets with anti-miR-26a-5p significantly enhanced COX-2 expression and PGE2 production ( p < .01), while HTPF treatment significantly inhibited anti-miR-26a-5p transfection-induced COX-2 expression or PGE2 production ( p < .05). These findings were further verified in pancreatic β-cells Min6. Moreover, the data also determined that HTPF also inhibits glucose-induced nuclear transcription factor (NF)-κB activity. Conclusion HTPF suppresses glucose-induced PGE2 production and activation of NF-κB via negative regulation of COX-2 and mmu-miR26a-5p. These novel pharmacological actions of HTPF on glucose-stimulated pancreatic islets provide new suggestions that HTPF or HTPF-derived compounds inhibit glucose induced inflammation in pancreas by up-regulating the expression of microRNAs.

The coronavirus disease-2019 (COVID-19) is a global public health disaster imposing a nationwide lockdown. This study was undertaken to determine the impact of COVID-19 quarantine on physical, nutritional, psychosocial life, and work aspects on the population of Saudi Arabia.Data collection was based on the fear of COVID-19 Scale (FCV-19S) and was analyzed by the Likert-type scale. A total of 2828 individuals participated during their COVID-19 quarantine. The data were collected during June 10-17, 2020 using the psychosocial FCV-19S.COVID-19 quarantine was negatively correlated with the physical, nutritional, psychosocial life and work aspects of the Saudi Arabia's population (The lockdown period was associated with an increase in the COVID-19 fear score. The degree FCV-19S was varied in different categories in several aspects. Low levels of physical activity and weight gained were observed during the lockdown period.

This study was undertaken to investigate an association between genetic variants of ERCC2 (Lys751Gln), ERCC2 (Asp312Asn) or XRCC1 (Arg399Gln) polymorphisms with the risk of prostate cancer (PC) in Saudi population. This is a case-control study conducted on 124 PC patients and 425 healthy human controls. Blood samples were used for DNA extraction and gene polymorphisms for ERCC2 (Lys751Gln), ERCC2 (Asp312Asn) and XRCC1 (Arg399Gln). The risk of the associations was calculated by odds ratio (OR) and 95% confidence interval (CI). The data demonstrated no significant associations between ERCC2 (Lys751Gln) polymorphism and PC risk, whereas ERCC2 (Asp312Asn) and XRCC1 (Arg399Gln) polymorphisms were found to be significantly associated with PC risk (OR of 2.2, 95% CI, 1.1–4.1; p = 0.02) and (OR of 2.4, 95% CI, 1.3–4.5; p = 0.005), respectively. Likewise, recessive genotype models also showed significant association of ERCC2 (Asp312Asn) and XRCC1 (Arg399Gln) polymorphisms with PC risk (p = 0.009). Interestingly, these genetic associations were more pronounced in aged populations (p = 0.003) as well as in smokers (p

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Abnormal post-transcriptional modulations in inflammatory genes by microRNAs (miRNAs) play a crucial role in human disorders including arthritis. In this study, we determined the effect of hsa-miR-125b-5p on interleukin (IL)-1β induced inflammatory genes in human osteoarthritic (OA) chondrocytes. Bioinformatics algorithms showed 3′untranslated region (3′UTR) of TRAF6 mRNA (NM_004620.3) has perfectly matched ‘seed-sequence’ for hsa-miR-125b-5p. Treatment of cells with IL-1β up-regulates TRAF6 mRNA and down-regulates hsa-miR-125b-5p expression. This negative correlation between TRAF6 and hsa-miR-125b-5p was verified by transfection with miR-125b mimic (pre-miR-125b). Moreover, transfection with miR-125b mimic caused marked inhibition of IL-1β-induced phosphorylation of p38-MAPK, JNK-MAPKs and ERK-MAPKs and also suppressed the nuclear levels of NF-κBp50, NF-κBp65 and inhibited the activation of IκBα. Furthermore, transfected chondrocytes with miR-125b mimic in the presence of IL-1β also showed marked inhibition in the secretion of several proinflammatory cytokines, chemokines and growth factors including IL-6, IL-8, INF-γ, TGF-β1, IGFBP-1 and PGDF-BB. Importantly, this transfection also significantly inhibited IL-1β- induced MMP-13 expression/production. In short, this study concludes that hsa-miR-125b-5p acts as a negative co-regulator of inflammatory genes including MMP-13 via targeting TRAF6/MAPKs/NF-κB pathway in human OA chondrocytes.

MicroRNAs (miRNAs) are short, non-coding RNAs involved in almost all cellular processes. Epigallocatechin-3-O-gallate (EGCG) is a green tea polyphenol and is known to exert anti-arthritic effects by inhibiting genes associated with osteoarthritis (OA). This study was undertaken to investigate the global effect of EGCG on interleukin-1β (IL-1β)-induced expression of miRNAs in human chondrocytes. Human chondrocytes were derived from OA cartilage and then treated with EGCG and IL-1β. Human miRNA microarray technology was used to determine the expression profile of 1347 miRNAs. Microarray results were verified by taqman assays and transfection of chondrocytes with miRNA inhibitors. Out of 1347 miRNAs, EGCG up-regulated expression of 19 miRNAs and down-regulated expression of 17 miRNAs, whereas expression of 1311 miRNAs remains unchanged in IL-1β-stimulated human OA chondrocytes. Bioinformatics approach showed that 3`UTR of ADAMTS5 mRNA contains the ‘seed-matched-sequence’ for hsa-miR-140-3p. IL-1β-induced expression of ADAMTS5 correlated with down-regulation of hsa-miR-140-3p. Importantly, EGCG inhibited IL-1β-induced ADAMTS5 expression and up-regulated the expression of hsa-miR-140-3p. This EGCG-induced co-regulation between ADAMTS5 and hsa-miR-140-3p becomes reversed in OA chondrocytes transfected with anti-miR-140-3p. This study provides an important insight into the molecular basis of the reported anti-arthritic effects of EGCG. Our data indicate that the potential of EGCG in OA chondrocytes may be related to its ability to globally inhibit inflammatory response via modulation of miRNAs expressions.

    The developed world’s aging population has experienced a dramatic increase in the incidence of joints dysfunction. Osteoarthritis (OA) is the most common forms of joints disorder that has a major impact on the patient's quality of life. The most important risk for OA besides female sex, obesity, and joint trauma is aging. (1) OA is characterized by joint pain, tenderness, limitation of movement, variable degrees of inflammation, etc. The mechanisms responsible appear to be multifactorial and are poorly understood. (1, 2) Recent therapeutic advancements in understanding of molecular and cellular mechanisms of joint disorders have highlighted the strategies that aim to inhibit the harmful effects of up-regulated inflammatory mediators and to inhibit their associated signaling events. (3, 4) Activated p38-mitogen activated protein kinase (p38-MAPK), c-Jun N-terminal kinases (JNK) and nuclear factor (NF)-IoB pathways regulate pro-inflammatory genes such as cyclooxygenease (COX)-2, inducible nitric oxide synthase (iNOS), matrix metallo-proteinases (MMPs), etc. and are major targets of drug discovery in OA. (4-6) (Fig.1). Although OA is present in every population but the treatment is still limited to a few classes of drugs, primarily non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids. While providing relief from pain, however, none of these drugs has been shown to inhibit cartilage breakdown or to inhibit disease progress; they also have varying degrees of gastrointestinal toxicity, ulcers, cardiovascular adverse effects, etc. (7) Therefore novel, safe and non-toxic anti-OA-therapies are needed that retard disease progression at an earlier stage and delay/prevent the need for joint replacement.     Natural products use by patients to alleviate symptoms is now rising globally. However, the quality of these products is poorly regulated and their efficacy, toxicity and mechanisms of action are largely unknown. (8) Pomegranate fruit ( Punica granatum L.) is used in traditional medicines for the treatment of patients with high blood pressure, high glucose, high cholesterol, oxidative stress, and inflammatory activities. Studies have shown that the pomegranate fruit rich in bioactive compounds such as polyphenols, anthocyanin, flavonoids, etc . (9) The use of pomegranate juice is increasing in popularity because of its high antioxidant content and is known to help in the prevention of cardiovascular disorders. (9,10) For the last decade, Haqqi and colleagues working on    I and some of my colleagues (16) demonstrated for the first time that human chondrocytes expressed the p38-MAPK isoforms p38I±, -I³ and -I´, but not p38I²-MAPK. Moreover, IL-1I² enhances the phosphorylation of the p38I±- and p38I³- MAPK isoforms but not of p38I´-MAPK. We also showed by gene silencing that p38-MAPK activation was mediated by upstream MAPK kinase 3 (MKK3). (16) Importantly, in the same study we also demonstrated that PFE selectively inhibited the IL-1I²-induced activation of MKK3, p38I±-MAPK isoform and DNA binding activity of runt-related transcription factor 2 (Runx2). (16) Runx2-deficient mice with OA showed reduced cartilage destruction and MMP-13 expression. (8, 17) Moreover, Runx2 regulates induction of genes of major cartilage degrading enzymes MMP-13 and ADAMTS-5 (A disintegrin and metalloproteinase with thrombospondin motifs 5), (18) whose inhibition by PFE could potentially reduce cartilage degradation. In another study, we demonstrated that PFE significantly inhibited the excessive production of IL-6 and IL-8 via suppression of the JNK-, extracellular signal-regulated kinases (ERK)- MAPKs and NF-IoB-signaling events. (19) All possible PFE target on IL-1I²-induced signaling cascade in human OA chondrocytes has been summarized in Figure 1. Thus, beneficial effects of PFE may be through these important therapeutic targets. Studies have also shown that oil extracted from pomegranate seeds is rich in punicic acid and has anti-arthritic activity. (9, 20) Experiments on arthritic animals conclude that consumption of pomegranate seed oil in diet increases the bone mineral density and inhibits the pro-inflammatory activities. (20)  Unlike NSAIDs or corticosteroids drugs that are currently in use for OA treatment, are having severe side effects, pomegranate in all forms has no side effects and are considered to be safe and non-toxic. Thus pomegranate or pomegranate-derived compounds can be emerged as novel therapeutic use for the treatment of OA and other degenerative/inflammatory diseases. In view of identified pharmacological targets and therapeutic potentials of pomegranate, clinical trials are in progress to explore its therapeutic potential for OA treatment, thus it may be anticipated that many of the open issues about the biological effect of pomegranate will be answered in the near future.pomegranate fruit whose therapeutic potentials, and mode of action on cartilage degenerative mechanisms to understand the pivotal molecular targets involved in inflammation and the joint destruction process for OA management. (11-14) They have shown that a standardized pomegranate fruit extract (PFE) is highly effective in exerting human cartilage sparing effects and is non-toxic to human cartilage cells. Pretreatment of human OA chondrocytes with PFE inhibited IL-1I²-induced expression of MMP 1, 3, and 13, which are classical markers of inflammation and cartilage degradation in arthritic joints. (11) In another study Haqqi and colleagues (12) demonstrated that oral administration of commercially prepared PFE (POMx) in inflammatory arthritis mouse model protects joints from inflammatory arthritis. They have shown that consumption of POMx potentially delayed the onset and reduced the incidence of inflammatory arthritis in mice. They also showed that in mouse macrophages, POMx abrogated multiple signal transduction pathways and downstream mediators implicated in the pathogenesis of arthritis. (12) Haqqi and colleagues also demonstrated that bioavailable constituents and/or metabolites of PFE exert an anti-inflammatory effect by inhibiting the activity of eicosanoid generating enzyme COX-2 and the production of nitric oxide, (13) which are key mediators for inflammation in OA. This further suggests that consumption of pomegranate may be of value in inhibiting inflammatory stimuli-induced cartilage breakdown and production of inflammatory mediators in arthritis. The cartilage protective effects by PFE were reconfirmed by another study in the monoiodoactate-induced OA animal model. (15)

This study was undertaken to identify and characterize the globally expressed microRNAs (miRNAs) involved in interleukin-1β (IL-1β)-induced joint damage and to predict whether miRNAs can regulate the catabolic effects in osteoarthritis (OA) chondrocytes. Out of 1347 miRNAs analyzed by microarrays in IL-1β-stimulated OA chondrocytes, 35 miRNAs were down-regulated, 1 miRNA was up-regulated, and the expression of 1311 miRNAs remained unchanged. Bioinformatics analysis showed the key inflammatory mediators and key molecular pathways are targeted by differentially expressed miRNAs. Novel miRNAs identified could have important diagnostic and therapeutic potentials in the development of novel therapeutic strategies for pain managements in OA.

Inducible nitric oxide synthase (iNOS) expression is associated with the pathogenesis of osteoarthritis (OA). This study was undertaken to investigate whether interleukin-1β (IL-1β)-mediated induction of iNOS can be regulated by microRNA-26a-5p (hsa-miR-26a-5p) in OA. Bioinformatics approaches show that 3'UTR of iNOS mRNA contained the 'seed-matched-sequence' for hsa-miR-26a-5p. IL-1β-induced expression of iNOS correlated with the down-regulation of miR-26a-5p in human OA chondrocytes. hsa-miR-26a-5p directly suppressed the luciferase activity of 3'UTR-iNOS reporter clone. Transfection with pre-miR-26a-5p induced marked silencing of iNOS expression. Activation of NF-κB pathway down-regulated the expression of hsa-miR-26a-5p and induced iNOS expression. In short, this is the first report that shows hsa-miR-26a-5p is a direct regulator of iNOS expression in human chondrocytes. hsa-miR-26a-5p may be an important regulator of human cartilage homeostasis and a new target for OA therapy.

Atopic dermatitis (AD) is a chronic multifactorial inflammatory skin disease. The pathogenesis of AD remains unclear, but the disease results from dysfunctions of skin barrier and immune response, where both genetic and environmental factors play a key role. Recent studies demonstrate the substantial evidences that show a strong genetic association with AD. As for example, AD patients have a positive family history and have a concordance rate in twins. Moreover, several candidate genes have now been suspected that play a central role in the genetic background of AD. In last decade advanced procedures similar to genome-wide association (GWA) and single nucleotide polymorphism (SNP) have been applied on different population and now it has been clarified that AD is significantly associated with genes of innate/adaptive immune systems, human leukocyte antigens (HLA), cytokines, chemokines, drug-metabolizing genes or various other genes. In this review, we will highlight the recent advancements in the molecular genetics of AD, especially on possible functional relevance of genetic variants discovered to date.

Objective: Toxoplasma gondii ( T. gondii) is a life-threatening parasite particularly infecting the immunocompromised women. Deficiency of vitamin D is well reported in several infectious disorders. This study was undertaken to investigate a correlation of vitamin D deficiency with the onset of T. gondii infection in immunocompetent women from the central of Saudi Arabia. Methods: Blood samples were collected from 304 Saudi women from the Qassim region of Saudi Arabia. Specific immunoassays were used to determine the levels of T. gondii immunoglobulin G and vitamin D. The SPSS and the Prism Graph Pad statistical software were used for the data analysis. Results: Out of 304 women, 18.8% were found to be positive for toxoplasmosis. Interestingly, the serum levels of vitamin D in toxoplasma positive cases were found to be significantly low as compared with the levels of vitamin D in toxoplasma negative cases. Moreover, sociodemographic risk factors such as age, residence location, and consumption of fruits/vegetables were also found to be associated with vitamin D deficiency and with the seroprevalence of toxoplasmosis. Conclusion: This study investigated a direct correlation of vitamin D deficiency with the severity of the toxoplasmosis in Saudi women. Therefore, it is predicted that vitamin D supplementation may provide protection against toxoplasma infection.

Objectives: To determine the frequency of antibody seropositivity of Toxoplasma gondii infection in a cancer patient population. We also explored on association of Toxoplasma gondii seropositivity with selected variables. Methods: This is a prospective cross-sectional study conducted at Prince Faisal bin Bandar cancer center, Qassim, Saudi Arabia, from November 2014 to March 2015. One hundred thirty seven patients were involved in the study. Demographic data was collected using structured questionnaire, and clinical information was retrieved from the patient’s medical reports. Enzyme-linked immunosorbent assay technique was used for antibody assay. Results : The frequency of seropositivity for Toxoplasma gondii infection was 30.6%. The patient’s age range from 1.5-84 years with a geometric mean of 42.7 years. The seropositivity was significantly higher ( p

During first trimester of human pregnancy, the maternal system develops immunity against infection and to provide protection of allogeneic foetus from abortion. This study was undertaken to determine the role of trophoblast specific CD74 isoforms in first trimester trophoblast derived cells under normal and lipopolysaccharide (LPS) stimulated conditions.Gene and protein of CD74 were determined in first trimester trophoblast derived cells, JEG-3 and ACH-3 P and also in human placenta by PCR, western blotting and immunoprecipitation. Effect of LPS mediated infection on the regulation of CD74 isoforms was studied intracellularly and also on the cells surface by flow cytometry.Data demonstrated that JEG-3 and ACH-3 P cells under normal conditions have not expressed CD74 isoforms neither intracellularly or nor on the surface. These results were further validated directly in human placenta. However, treatment of these trophoblast cells with a bacterial LPS, significantly upregulated CD74 mRNA expression (p0.05). Furthermore, expression of CD74 on the surface was not detected even after stimulation with LPS. Interestingly, CD74 isoform at 35 kDa was significantly detected intracellularly upon stimulation with LPS (p0.05). These results were further confirmed by western blotting followed by immunoprecipitation.To the best of our knowledge, this is the first study concluded that the bacterial LPS induce infection in the first trimester trophoblasts via intracellular upregulation of CD74. Data indicated that the lack of cell surface expression of trophoblastic specific isoforms of CD74 may provide protection for human pregnancy in the first trimester.

Background Allergic reactions have been implicated as contributions in a number of atopic disorders, including atopic dermatitis (AD), allergic rhinitis (AR) and bronchial asthma (BA). However, the potential for filaggrin protein, eosinophil major basic protein (MBP) and immunoglobulin E (IgE) to elicit allergic response or to contribute to atopic disorders remains largely unexplored in pediatric patients. This study was undertaken to investigate the status and contribution of filaggrin protein, eosinophil MBP and total IgE in pediatric patients with AD, AR and BA. Methods Sera from 395 pediatric patients of AD, AR or BA with varying levels of disease activity according to the disease activity index and 410 age-matched non-atopic healthy controls were evaluated for serum levels of atopic markers, including filaggrin, eosinophil MBP and IgE. Results Serum analysis showed that filaggrin levels were remarkably high in pediatric patients with AD, followed by BA and AR, whereas its levels were low in non-atopic pediatric controls. Eosinophil MBP levels in sera of atopic patients were significantly high as compared with their respective controls, but its levels were highest in AR patients, followed by AD and BA. Total IgE in sera of AD patients was markedly high, followed by AR and BA patients, whereas its levels were low in non-atopic pediatric controls. Interestingly, not only was an increased number of subjects positive for filaggrin protein, eosinophil MBP or total IgE, but also their levels were statistically significantly higher among those atopic patients whose disease activity scores were higher as compared with atopic patients with lower disease activity scores. Conclusions These findings strongly support a role of filaggrin protein, eosinophil MBP and IgE in the onset of allergic reactions in pediatric patients with AD, AR and BA. The data suggest that filaggrin, eosinophil MBP or IgE might be useful in evaluating the progression of AD, AR or BA and in elucidating the mechanisms involved in the pathogenesis of these pediatric disorders.

Objectives: To investigate the role of reactive-oxygen-species (ROS) induced epitopes on human-serum-albumin (HSA) and thyroid antigens in psoriasis autoimmunity. Methods: This study was performed in the College of Medicine, Qassim University, Buraidah, Saudi Arabia between May 2014 and February 2015. The study was designed to explore the role of ROS-induced epitopes in psoriasis autoimmunity. Singlet-oxygen (or ROS)-induced epitopes on protein (ROS-epitopes-albumin) was characterized by in-vitro and in-vivo. Thyroid antigens were prepared from rabbit thyroid, and thyroglobulin was isolated from thyroid extract. Immunocross-reactions of protein-A purified anti-ROS-epitopes-HSA-immunoglobulin G (IgGs) with thyroid antigen, thyroglobulin, and their oxidized forms were determined. Binding characteristics of autoantibodies in chronic plaque psoriasis patients (n=26) against ROS-epitopes-HSA and also with native and oxidized thyroid antigens were screened, and the results were compared with age-matched controls (n=22). Results: The anti-ROS-epitopes-HSA-IgGs showed cross-reactions with thyroid antigen, thyroglobulin and with their oxidized forms. High degree of specific binding by psoriasis IgGs to ROS-epitopes-HSA, ROS-thyroid antigen and ROS-thyroglobulin was observed. Immunoglobulin G from normal-human-controls showed negligible binding with all tested antigens. Moreover, sera from psoriasis patients had higher levels of carbonyl contents compared with control sera. Conclusion: Structural alterations in albumin, thyroid antigens by ROS, generate unique neo-epitopes that might be one of the factors for the induction of autoantibodies in psoriasis. Saudi Med J 2015; Vol. 36 (12): 1408-1419 doi: 10.15537/smj.2015.12.12612

Vitiligo is a common pigmentary disorder, the precise etiology of which remains obscure. Tyrosinase, a key enzyme involved in melanin synthesis, has now been implicated as an autoantigen for vitiligo patients, but it is not clear how this prevalent protein becomes antigenic in vitiligo.To investigate the status and contribution of oxidized tyrosinase in vitiligo and to explore whether oxidized tyrosinase has a role in disease progression.Tyrosinase was modified by reactive-oxygen-species (ROS). Binding characteristics of antibodies in vitiligo patients (n=25) with varying disease duration (DD) and disease severity were screened against ROS-modified tyrosinase (ROS-tyrosinase) by immunoassays and their results were compared with healthy controls (n=23).The ROS caused extensive alterations in conformation and function of tyrosinase. Protein-A purified IgGs from vitiligo patients (Vt-IgG) showed strong binding to ROS-tyrosinase in comparison with IgGs from healthy controls (p0.001). Interestingly, not only was there an increased number of subjects positive for anti-ROS-tyrosinase-IgGs, but also the levels of these IgGs were significantly higher among vitiligo patients, whose DD were ≥10 years as compared to patients with short DD (10 years). In addition, a significant correlation was observed between the levels of anti-ROS-tyrosinase-IgGs and the patients' ages or with disease severity. Experimentally induced anti-ROS-tyrosinase-IgGs show reactivity with tyrosinase from vitiligo patients. Furthermore, vitiligo patients had lower levels of tyrosinase activity compared with healthy controls. Not only these, levels of carbonylation were also higher among vitiligo patients whose DD were ≥10 years as compared to patients with DD10 years.This is the first study to demonstrate the role of oxidized tyrosinase in vitiligo. Our novel results support an association between oxidized tyrosinase and vitiligo autoimmunity. The stronger antibodies response to oxidized tyrosinase in vitiligo patients with higher DD or with severe patients suggests that oxidized tyrosinase may be a useful biomarker in evaluating the progression of vitiligo and in elucidating the mechanisms of disease pathogenesis.