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.
BACKGROUND: Medical students in their academic years are generally under stress but very few studies revealed the relationship between the stress and how the students manage to adapt these stressful conditions.
AIM: The aim of the study was to investigate the levels of stress and their adaptive coping in the 1st 3 years medical students and also to determine the factors associated with adaptive coping strategies.
METHODS: This is a descriptive cross-sectional study conducted on 441 medical students of Qassim University from September-October 2019. First 3 years medical students were randomly selected and their stress levels or adaptive coping strategies were determined by general health questionnaire (GHQ-12) and strategies coping mechanisms (SCM), respectively. The 5-points Likert scale was used for scoring and the data obtained were further validated by DASS and Brief COPE scales.
RESULTS: Out of 441 medical students, 39.2% agreed to participate. The data showed that the level of stress among students was highest during their 1st year academic blocks, followed by 2nd and 3rd year students. Interesting, the adaptive coping among them was found highest during the academic blocks of 3rd year students, followed by the 2nd and 1st year students. Importantly, female students showed better adaptation against stress. Students living with their parents avoided stress in better ways as compared to those who were living alone.
CONCLUSION: This is the first study that shows an inverse correlation between the stress and adaptive coping in medical students of Qassim University. The data concluded that adaptation of stress in the 3rd-year students was the highest followed by 2nd and 1st year medical students. Moreover, female students adapted well against stress and students living alone showed worse adaptation of stress.
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.
Abstract Several recent studies have documented that supplementation with pomegranate fruit extract inhibits inflammatory symptoms in vivo . However, the molecular basis of the observed effects has not been fully revealed. Although previous studies have documented the inhibition of nitric oxide and cyclooxygenase (COX) activity in vitro by plant and fruit extracts added directly into the culture medium but whether concentrations of bioactive compounds sufficient enough to exert such inhibitory effects in vivo can be achieved through oral consumption has not been reported. In the present study we determined the effect of rabbit plasma obtained after ingestion of a polyphenol rich extract of pomegranate fruit (PFE) on COX enzyme activity ex vivo and the IL-1β-induced production of NO and PGE 2 in chondrocytes in vitro . Plasma samples collected before and 2 hr after supplementation with PFE were tested. Plasma samples collected after oral ingestion of PFE were found to inhibit the IL-1β-induced PGE 2 and NO production in chondrocytes. These same plasma samples also inhibited both COX-1 and COX-2 enzyme activity ex vivo but the effect was more pronounced on the enzyme activity of COX-2 enzyme. Taken together these results provide additional evidence of the bioavailability and bioactivity of compounds present in pomegranate fruit after oral ingestion. Furthermore, these studies suggest that PFE-derived bioavailable compounds may exert an anti-inflammatory effect by inhibiting the inflammatory cytokine-induced production of PGE 2 and NO in vivo .
Abstract 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 < 0.05). Furthermore, a strong association was observed between the susceptibility of 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.
Bioinformatics is an important approach for the management of biological data on a larger scale. It is basically an emerging interdisciplinary field of modern biotechnology that develops methods and software’s for understanding of biological data. For data analysis or interpretations, bioinformatics utilizes in-silico approach to answer the biomedical questions using mathematical and statistical methods. 1 The basic objective of bioinformatics approach is storage of extensive molecular biology data in database forms. These data must be assigned in a ways to give suitable meaningful information in different grades. 1, 2 As for example, GenBank nucleotide sequence information, etc. Another objective of bioinformatics approach is data analysis. As of BLAST to analyze nucleotide sequence of same type to design primers or probes for polymerase chain reaction technique, etc. But the central objective of bioinformatics approach is to interpret extensive biomedical data, resulting to give meaningful biological information. 1, 2 So far, bioinformatics approach has got super success for the determination of nucleotide sequence alignment, gene expression prediction, prediction of protein structure, alignment of protein structure and also in studies of genome-wide association, assembly of genome and also for modeling of evolution. 1-3 MicroRNAs (miRNAs) are key regulators of genes at post-transcriptional level, they are basically single-stranded non-protein coding RNAs of just 20-25 nucleotides and now it is well documented that miRNAs are involved in almost all physiological and pathological mechanisms. 2, 4-8 According to the latest updates, 2588 mature miRNAs have been processed from 1881 precursor miRNAs in human genome (miRBase: http://www.mirbase.org/index.shtml , release #21, June 2014). Now it is well reported that miRNAs expression levels are widely distributed in humans; some are universally expressed while others are expressed in tissues and/or cells and now miRNAs network seems to be a complex regulatory network. 2, 4-10 As for example, individual miRNA can act on numerous target mRNAs and every mRNA can be targeted by multiple miRNAs that promotes numerous regulatory mechanisms. 2, 8 Altered miRNAs expression have been reported in almost all disorders and studies concluded that deregulation of miRNAs expression effects on the development and progression of many human disorders and now many investigators pointed out that miRNAs could serve as potential molecular biomarkers not only for disease detection but also for therapeutic application. 4-10 In order to develop the bioinformatics programs for the management of miRNA research data and to identify miRNA targets, the following prime features are often used: (1) base pairing pattern between miRNA and 3`untranslated region (3`UTR) of target mRNA sequence, (2) miRNA-mRNA duplex thermodynamic stability, (3) evolutionary conservation of target sites of miRNAs in different species, investigation of multiple target/binding sites. 2, 8 Recently, many bioinformatics algorithms have been introduced for the management of miRNA research data. Most of these are utilizing different features for the identification or validation of individual miRNA, prediction of miRNAs target sequences, identification of miRNA expression, miRNAs signaling pathways determination, determination of miRNA metabolic pathways, analysis of regulatory networks of miRNAs, identification of miRNA-transcription factor interplay and investigation of miRNA link to human disorders. 2, 8-10 Although all online available bioinformatics approaches have been well studied and revised by many investigators, 2, 8-10 but here a briefly description of most user friendly approaches are given, which are widely used in miRNA research. (1) TargetScan and TargetScan S algorithms: TargetScan and TargetScanS are two different algorithms of online available TargetScan program. TargetScan is one of the most common user friendly programs based on the two classic features for miRNA target prediction. First is the seed-match sequence between miRNA and 3`UTR of target gene using base-pairing rule and other feature of this algorithm is free energy. Whereas, TargetScanS is an updated version of TargetScan, in contrast to TargetScan, TargetScanS does not use free energy feature for miRNA targets prediction. Recent data showed that the false positive rate by TargetScanS is reduced from 30% to 22%. 2, 8 (2) DIANA-microT-CDS algorithm: It is an excellent algorithm with user-friendly interface for miRNA target prediction. It is basically an updated version of DIANA-microT algorithm, which predict miRNA target by the combination computational and experimental algorithms. This bioinformatics approach considers the following features such as binding group mass, closest distance of end of the coding sequences or closest distance of 3`UTR to an adjacent binding site, AU content and conservation and also it utilizes free energy of miRNA and target hybrid. This web based algorithm utilizes an extensive connectivity to numerous web-based biological servers, which provide us collective information of the predicted miRNA-target hybrid interaction. 2, 8 (3) PicTar algorithm: This algorithm requires the feature of binding sites which are co-regulated by multiple miRNA across species. It basically investigates the binding alignments of 3`UTRs of target genes to miRNAs and it also filters the binding alignments via thermodynamic stability of miRNA-target hybrid. 2, 8 (4) miRanda algorithm: This algorithm also utilizes two features for miRNA target prediction, which are nucleotides complementarity and binding energy of the duplex. In first step, miRanda algorithm utilizes Watson-Crick and G-U matching rule between aligned miRNA and 3`UTR of target gene and in second step it calculates the binding energy of miRNA-sites duplex by Vienna package. 8 (5) RNAhybrid algorithm: This algorithm predicts multiple miRNA targets in large 3' UTRs of target genes. It basically uses three features such as seed matching, free energy feature and an additional feature of free energy of p -value. 2,8 There are many others bioinformatics algorithms for miRNA target predictions such as PITA, Tarbase, rna22, MiRDB, STarMir, microInspector, Mirpath, MaMi, MiRecords, mirDIP, miRGator, Magia, miRTar, miR Trail, etc. all utilize different modes for the detection of miRNA target genes in humans, which are extensively reviewed. 2, 8-10 All of these above information of bioinformatics approaches clearly indicated that all current approaches are based on different operational modes and models for target predictions, therefore it is important for the researcher to check the underlying strengths and weakness of a bioinformatics tools before use. So far, targetScan, DIANA-microT-CDs and miRanda are highly adopted with the most common user-friendly interface, whereas PicTar, RNA hybrid are also accepted by the miRNA researchers. However, it is also suggested that combining results from multiple approaches is always encouraged to minimize the chances of errors and to reduce the negative outputs. As miRNAs are involved in almost all human biological mechanisms and their deregulation have been reported in the pathogenesis of numerous human disorders such as cancer, arthritis, etc. and now it seems that miRNAs research has a valuable impact on human health. 2, 4-10 In spite of these important implications of miRNA research in the pathogenesis of human disorders, but still huge scale of deregulatory mechanisms of miRNA remains unknown. Introduction of bioinformatics approaches in miRNA research is making possible to address a variety of aspects of ongoing miRNA researches. Investigators from all over the world have reviewed almost all major and minor resources of bioinformatics tools, which are now applicable in miRNA research, that cover all aspects of miRNA target predictions to their functional implications. In contrast, these approaches are still having limitations, which are needed to be addressed. The most common and vital flaw of these approaches is the generation of false-positive data on a large scale. 2, 8 Therefore, there is an urgent requirement to refine these machine-learning-based algorithms which will minimize these flaws. As dysfunctioning of miRNAs are frequently reported in almost all human disorders and now it is well established that miRNA are considered to be the most suitable therapeutic targets for the management of human disorders, bioinformatics tools in the next generation biomedical research will greatly benefit to handle the massive flow of miRNA data and to provide us an accurate miRNA target prediction algorithm which will solve the secretes of miRNAs association with human disorders.
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