Absence of CD74 Isoform at 41kDa Prevents the Heterotypic Associations between CD74 and CD44 in Human Lung Adenocarcinoma-derived Cells.

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 E2 (PGE2) 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 PGE2 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 PGE2 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.

Epigallocatechin-3-O-gallate modulates global microRNA expression in interleukin-1ß-stimulated human osteoarthritis chondrocytes: potential role of EGCG on negative co-regulation of microRNA-140-3p and ADAMTS5.

PURPOSE: 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-1ß (IL-1ß)-induced expression of miRNAs in human chondrocytes. METHODS: Human chondrocytes were derived from OA cartilage and then treated with EGCG and IL-1ß. 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. RESULTS: 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-1ß-stimulated human OA chondrocytes. Bioinformatics approach showed that 3`UTR of ADAMTS5 mRNA contains the 'seed-matched-sequence' for hsa-miR-140-3p. IL-1ß-induced expression of ADAMTS5 correlated with down-regulation of hsa-miR-140-3p. Importantly, EGCG inhibited IL-1ß-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. CONCLUSIONS: 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.

Epigallocatechin-3-O-gallate up-regulates microRNA-199a-3p expression by down-regulating the expression of cyclooxygenase-2 in stimulated human osteoarthritis chondrocytes.

Osteoarthritis (OA) is a most common form of arthritis worldwide leading to significant disability. MicroRNAs (miRNAs) are non-coding RNAs involved in various aspects of cartilage development, homoeostasis and pathology. Several miRNAs have been identified which have shown to regulate expression of target genes relevant to OA pathogenesis such as matrix metalloproteinase (MMP)-13, cyclooxygenase (COX)-2, etc. Epigallocatechin-3-O-gallate (EGCG), the most abundant and active polyphenol in green tea, has been reported to have anti-arthritic effects, however, the role of EGCG in the regulation of miRNAs has not been investigated in OA. Here, we showed that EGCG inhibits COX-2 mRNA/protein expression or prostaglandin E2 (PGE2 ) production via up-regulating microRNA hsa-miR-199a-3p expression in interleukin (IL)-1ß-stimulated human OA chondrocytes. This negative co-regulation of hsa-miR-199a-3p and COX-2 by EGCG was confirmed by transfection of OA chondrocytes with anti-miR-199a-3p. Transfection of OA chondrocytes with anti-miR-199a-3p significantly enhanced COX-2 expression and PGE2 production (P < 0.001), while EGCG treatment significantly inhibited anti-miR-199a-3p transfection-induced COX-2 expression or PGE2 production in a dose-dependent manner. These results were further re-validated by co-treatment of these transfection OA chondrocytes with IL-1ß and EGCG. EGCG treatment consistently up-regulated the IL-1ß-decreased hsa-miR-199a-3p expression (P < 0.05) and significantly inhibited the IL-1ß-induced COX-2 expression/PGE2 production (P < 0.05) in OA chondrocytes transfected with anti-hsa-miR-199a-3p. Taken together, these results clearly indicate that EGCG inhibits COX-2 expression/PGE2 production via up-regulation of hsa-miR-199a-3p expression. These novel pharmacological actions of EGCG on IL-1ß-stimulated human OA chondrocytes provide new suggestions that EGCG or EGCG-derived compounds inhibit cartilage breakdown or pain by up-regulating the expression of microRNAs in human chondrocytes.

MicroRNA-26a-5p regulates the expression of inducible nitric oxide synthase via activation of NF-κB pathway in human osteoarthritis chondrocytes.

Inducible nitric oxide synthase (iNOS) expression is associated with the pathogenesis of osteoarthritis (OA). This study was undertaken to investigate whether interleukin-1ß (IL-1ß)-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-1ß-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.

Stress-mediated modulations in dopaminergic system and their subsequent impact on behavioral and oxidative alterations: an update.

CONTEXT: Stress-induced changes in the dopaminergic system and subsequent enhancement of oxidative load and behavior are associated with a wide range of central and peripheral nervous disorders. Dopamine acts as a key neurotransmitter in the brain plays an important role in the regulation of motor and limbic functions. OBJECTIVE: This article reviews the effect of stress on central dopaminergic system and its subsequent impact on the alterations in behavior and oxidative stress. METHODS: A literature survey in PubMed (Bethesda, MD), Scopus (Philadelphia, PA), SciFinder (Columbus, OH) and Google Scholar (PMV, CA) was performed to gather information regarding the role of stress on central dopaminergic system and its associated behavioral and oxidative alterations. RESULTS: Our collective data on behavioral studies and oxidative distress in stressful conditions show the functional reduction in dopaminergic neuronal system that could be one of the factors for the development of stress-induced motor suppression. Collectively, stress caused significant behavioral and oxidative alterations via suppression of neuronal functions of the central dopaminergic system. CONCLUSIONS: This study provides an insight into the overall pathophysiological alterations in neuronal functions of the central dopaminergic system caused by acute and chronic unpredictable stress that, in our opinion, represent optimal utility as future therapeutic targets for neurodegenerative disorders.

Gold nanoparticles attenuate the interferon-γ induced SOCS1 expression and activation of NF-κB p65/50 activity via modulation of microRNA-155-5p in triple-negative breast cancer cells.

Objective: Triple-negative breast cancer (TNBC) is a very aggressive form of cancer that grows and spreads very fast and generally relapses. Therapeutic options of TNBC are limited and still need to be explored completely. Gold nanoparticles conjugated with citrate (citrate-AuNPs) are reported to have anticancer potential; however, their role in regulating microRNAs (miRNAs) in TNBC has never been investigated. This study investigated the potential of citrate-AuNPs against tumorigenic inflammation via modulation of miRNAs in TNBC cells. Methods: Gold nanoparticles were chemically synthesized using the trisodium-citrate method and were characterized by UV-Vis spectrophotometry and dynamic light scattering studies. Targetscan bioinformatics was used to analyze miRNA target genes. Levels of miRNA and mRNA were quantified using TaqMan assays. The pairing of miRNA in 3'untranslated region (3'UTR) of mRNA was validated by luciferase reporter clone, containing the entire 3'UTR of mRNA, and findings were further re-validated via transfection with miRNA inhibitors. Results: Newly synthesized citrate-AuNPs were highly stable, with a mean size was 28.3 nm. The data determined that hsa-miR155-5p is a direct regulator of SOCS1 (suppressor-of-cytokine-signaling) expression and citrate-AuNPs inhibits SOCS1 mRNA/protein expression via modulating hsa-miR155-5p expression. Transfection of TNBC MDA-MB-231 cells with anti-miR155-5p markedly increased SOCS1 expression (p<0.001), while citrate-AuNPs treatment significantly inhibited anti-miR155-5p transfection-induced SOCS1 expression (p<0.05). These findings were validated by IFN-γ-stimulated MDA-MB-231 cells. Moreover, the data also determined that citrate-AuNPs also inhibit IFN-γ-induced NF-κB p65/p50 activation in MDA-MB-231 cells transfected with anti-hsa-miR155-5p. Conclusion: Newly generated citrate-AuNPs were stable and non-toxic to TNBC cells. Citrate-AuNPs inhibit IFN-γ-induced SOCS1 mRNA/protein expression and deactivate NF-κB p65/50 activity via negative regulation of hsa-miR155-5p. These novel pharmacological actions of citrate-AuNPs on IFN-γ-stimulated TNBC cells provide insights that AuNPs inhibit IFN-γ induced inflammation in TNBC cells by modulating the expression of microRNAs.

Brain region specific monoamine and oxidative changes during restraint stress.

BACKGROUND AND PURPOSE: Stress-induced central effects are regulated by brain neurotransmitters, glucocorticoids and oxidative processes. Therefore, we aimed to evaluate the simultaneous alterations in the monoamine and antioxidant systems in selected brain regions (frontal cortex, striatum and hippocampus) at 1 hour (h) and 24h following the exposure of restraint stress (RS), to understand their initial response and possible crosstalk. METHODS AND RESULTS: RS (150 min immobilization) significantly increased the dopamine levels in the frontal cortex and decreased them in the striatum and hippocampus, with selective increase of dopamine metabolites both in the 1h and 24h RS groups compared to control values. The serotonin and its metabolite levels were significantly increased in both time intervals, while noradrenaline levels were decreased in the frontal cortex and striatum only. The activities of superoxide dismutase, glutathione peroxidase and the levels of lipid peroxidation were significantly increased with significant decrease of glutathione levels in the frontal cortex and striatum both in the 1h and 24h RS groups. There was no significant change in the catalase activity in any group. In the hippocampus, the glutathione levels were significantly decreased only in the 1h RS group. CONCLUSIONS: Our study implies that the frontal cortex and striatum are more sensitive to oxidative burden which could be related to the parallel monoamine perturbations. This provides a rational look into the simultaneous compensatory central mechanisms operating during acute stress responses which are particular to precise brain regions and may have long lasting effects on various neuropathological alterations.

Restraint stress-induced central monoaminergic & oxidative changes in rats & their prevention by novel Ocimum sanctum compounds.

BACKGROUND & OBJECTIVES: Ocimum sanctum (OS) is known to possess various therapeutic properties. We have earlier isolated and characterized three OS compounds; Ocimarin, Ocimumoside A and Ocimumoside B. However, their role in modulating stress-induced central changes is unexplored. Thus, the present study was aimed to investigate the effect of these OS compounds on restraint stress (RS)-induced changes in the monoaminergic and antioxidant systems in the frontal cortex, striatum and hippocampus of rats. METHODS: RS was produced by immobilizing (restraining) the Sprague Dawley rats for a period of 2.5 h inside cylindrical steel tubes. The monoamine levels and the in vivo antioxidant status in brain regions were evaluated by HPLC-EC and spectrophotometric assays, respectively. RESULTS: RS significantly increased the dopamine levels in the frontal cortex and decreased in the striatum and hippocampus, and accompanied with selective increase of dopamine metabolites compared to the NS control group. The serotonin and its metabolite levels were significantly increased, while noradrenaline levels were decreased by RS in the three brain regions studied. The activities of superoxide dismutase and glutathione peroxidase in the frontal cortex and striatum were significantly increased by RS with decreased glutathione levels and increased lipid peroxidation. Pre-treatment with Ocimumoside A and B (40 mg/kg po) for a period of 3 days prevented the RS-induced changes with an efficacy similar to that of standard anti-stress (Panax quinquefolium; 100 mg/kg po) and antioxidant (Melatonin; 20 mg/kg ip) drugs, while, Ocimarin failed to modulate these changes. OS compounds per se had no effect on these parameters. INTERPRETATION & CONCLUSIONS: The present findings showed the anti-stress potential of Ocimumoside A and B in relation to their simultaneous modulatory effects on the central monoaminergic and antioxidant systems implicating their therapeutic importance in stress-related disorders. Further studies are required to understand the mechanism of action of these compounds.

Thymoquinone provides structural protection of human hemoglobin against oxidative damage: Biochemical studies.

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.

Alterations in monoamine levels and oxidative systems in frontal cortex, striatum, and hippocampus of the rat brain during chronic unpredictable stress.

Stress plays a key role in the induction of various clinical disorders by altering monoaminergic response and antioxidant defenses. In the present study, alterations in the concentrations of dopamine (DA), serotonin (5-HT) and their metabolites, and simultaneous changes in the antioxidant defense system and lipid peroxidation in different brain regions (frontal cortex, striatum, and hippocampus) were investigated immediately and 24 h after exposure to chronic unpredictable stress (CUS). CUS involved subjecting Sprague-Dawley rats to two different types of stressors varying from mild to severe intensity every day in an unpredictable manner, over a period of 7 days. CUS significantly decreased DA and 5-HT concentrations, with increased DA turnover ratios in the selected brain regions. In the frontal cortex and striatum, DA metabolite concentrations were increased; however, in the hippocampus they remained unaltered. Further, a decrease of 5-hydroxyindoleacetic acid content was observed in the frontal cortex and striatum, with no significant alteration in the hippocampus. CUS also reduced the activities of superoxide dismutase and catalase, with increased lipid peroxidation and decreased glutathione levels in the selected brain regions. Glutathione peroxidase activity was increased in the frontal cortex and hippocampus only. The pattern of CUS-induced monoamine and oxidative changes immediately after the last stressor and 24 h later were similar when compared with the control group, indicating that the observed changes were due to the chronic exposure to the various stressors and were not merely acute effects of the last stressor. The altered redox state in the striatum and frontal cortex might be related to the perturbed DA and/or 5HT levels, while the hippocampus seems to be less influenced by CUS in terms of monoamine metabolite changes. These results suggest that the perturbed monoamine levels could interact with the oxidative load during CUS. Hence, the current study has implications for pharmacological interventions targeting both central monoamines and cellular antioxidants as a potential stress management strategy for protecting against central stress-induced disorders.

Differential response of central dopaminergic system in acute and chronic unpredictable stress models in rats.

We aimed to evaluate the response of dopaminergic system in acute stress (AS) and chronic unpredictable stress (CUS) by measuring dopamine (DA) levels, its receptor densities in the frontal cortex, striatum, hippocampus, amygdala and orbito-frontal cortex regions of rat brain, and investigated the corresponding behavioral locomotor changes. Involvement of D(1) receptor was also examined during AS and CUS using A 68930, a D(1) selective agonist. Rats were exposed to AS (single immobilization for 150 min) and CUS (two different stressors for 7 days). AS significantly decreased the DA levels in the striatum and hippocampus, and A 68930 pretreatment significantly reverted these changes. However, in the frontal cortex significantly increased DA levels were remain unchanged following A 68930. CUS led to a decrease of DA levels in the frontal cortex, striatum and hippocampus, which were normalized by A 68930. Saturation radioligand binding assays revealed a significant decrease in the number of D(1)-like receptors in the frontal cortex during CUS, which were further decreased by A 68930 pretreatment. However, in the striatum and hippocampus, A 68930 pretreatment reduced the CUS induced increase in the number of D(1)-like receptors. No significant changes were observed in the amygdala and orbito-frontal cortex during AS and CUS, while D(2)-like receptors were unchanged in all the brain regions studied. Locomotor activity was significantly decreased in both the stress models, A 68930 pretreatment significantly increased stereotypic counts and horizontal activity. Thus, present investigation provide insights into the differential regional response of dopaminergic system during AS and CUS. Further, neurochemical and behavioral effects of D(1) agonist pretreatment suggest specific modulatory role of D(1) receptor under such stressful episodes.

Melatonin protects against experimental reflux esophagitis.

Reflux esophagitis (RE), a major gastrointestinal disorder results from excess exposure of the esophageal mucosa to acidic gastric juice or bile-containing duodenal contents refluxed via an incompetent lower esophageal sphincter. Recent studies implicated oxygen derived free radicals in RE induced esophageal mucosal damage resulting in mucosal inflammation. Thus, control over free radical generation and modulation of inflammatory responses might offer better therapeutic effects to counteract the severity of RE. In this context we investigated the effect of melatonin against experimental RE in rats. Melatonin pretreatment significantly reduced the haemorrhagic lesions and decreased esophageal lipid peroxidation aggravated by RE. Moreover, the depleted levels of superoxide dismutase and glutathione observed in RE were replenished by melatonin signifying its free radical scavenging properties and antioxidant effects resulting in the improvement of esophageal defense mechanism. Further melatonin repressed the upregulated levels of expression of proinflammatory cytokines like, TNF-alpha, IL-1beta and IL-6 in RE. However, increased levels of the anti-inflammatory cytokine IL-10 remained unaltered after melatonin administration signifying its immunomodulatory effect through suppression of Th1-mediated immune responses. The involvement of receptor dependent actions of melatonin against RE were also investigated with MT2 receptor antagonist, luzindole (LUZ). LUZ failed to antagonize melatonin's protective effects against RE indicating that melatonin mediated these beneficial effects in a receptor-independent fashion. Thus, esophageal mucosal protection elicited by melatonin against experimental RE is not only dependent on its free radical scavenging activity but also mediated in part through its effect on the associated inflammatory events in a receptor-independent manner.

Elevated Levels of Protein Carbonylation in Patients With Diabetic Nephropathy: Therapeutic and Diagnostic Prospects.

BACKGROUND: Oxidative stress-induced protein oxidation has been reported in diabetes mellitus; however a relationship between protein carbonylation and diabetic nephropathy remains to be determined. This study was undertaken to investigate a correlation between protein carbonylation and diabetic nephropathy. METHODS: Sera from 153 patients with diabetic nephropathy and 142 healthy humans were selected and protein carbonylation was compared. The glycated hemoglobin (HbA1C), postprandial blood glucose (PPBG), disease duration (DD) and serum creatinine were analyzed and were correlated with the levels of protein oxidation. RESULTS: Protein carbonylation was more pronounced in patients with diabetic nephropathy as compared with healthy humans (P < 0.001). The data showed a positive correlation between protein oxidation and HbA1C (P < 0.001, r = 0.752); the carbonylation was high in those patients with high HbA1C (P < 0.01). The data also showed an important correlation between protein oxidation and PPBG (P < 0.0001, r = 0.680); the carbonyl contents were higher in those patients with higher PPBG (P < 0.001). Results also pointed out a positive correlation of protein oxidation with patients DD (P < 0.001, r = 0.769). Importantly, elevated levels of carbonylation in patients with diabetic nephropathy were also correlated with the elevated levels of serum creatinine. CONCLUSIONS: This is the first study that shows a positive correlation between protein carbonylation and diabetic nephropathy. The higher carbonylation in patients with higher HbA1C, blood glucose, DD or serum creatinine indicate that oxidative modifications in proteins play a key role in the progression of diabetic nephropathy.

MicroRNA-125b-5p regulates IL-1ß induced inflammatory genes via targeting TRAF6-mediated MAPKs and NF-κB signaling in human osteoarthritic chondrocytes.

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)-1ß 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-1ß 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-1ß-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-1ß also showed marked inhibition in the secretion of several proinflammatory cytokines, chemokines and growth factors including IL-6, IL-8, INF-γ, TGF-ß1, IGFBP-1 and PGDF-BB. Importantly, this transfection also significantly inhibited IL-1ß- 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.

Author Correction: MicroRNA-125b-5p regulates IL-1ß induced inflammatory genes via targeting TRAF6-mediated MAPKs and NF-κB signaling in human osteoarthritic chondrocytes.

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

Stress Associated Alterations in Dietary Behaviours of Undergraduate Students of Qassim University, Saudi Arabia.

BACKGROUND: Psychological stress associated eating habits among public health have now become a global concern. AIM: This study was undertaken to investigate the levels of psychological stress among undergraduate students of Qassim University and to explore the stress associated alterations in their eating habits. METHODS: This is a cross-sectional survey conducted on 614 undergraduate students of Qassim University, Saudi Arabia. A self-administered questionnaire was used, which included questions on socio-demography and eating habits. Level of stress was measured by a standardised questionnaire highlights the levels of non-chronic stimulation through difficulty relaxing, nervous arousal and being easily upset/agitated, irritable / over-reactive and impatient. RESULTS: Our results show that 28.2% of total participants suffered from some extent of stress. Among stressed participants, 17.3%, 49.1%, 24.8% and 8.7% of participants suffered from mild, moderate, severe and extremely severe stress, respectively. Stressed participants were more preferred to eat junk foods such as fast foods, snacks and beverages as compared with unstressed participants (p < 0.05) and the junk food preference was increased with the increase of stress levels. Moreover, non-stressed participants preferred more healthy foods such as vegetarian food, fresh fruits as compared with stressed participants (p < 0.05). Taste and easy to access were the main reasons for the preference of junk foods by the stressed participants. CONCLUSIONS: This is the first comprehensive study from Saudi Arabia to show stress associated dietary alterations in undergraduates of Qassim University. Data concluded that most of the young adults followed a healthy eating pattern, but a significant number from them were affected by stress. Therefore, specific intervention programs are strongly recommended for the reduction of stress and to improve their quality of life.

Bisphenol A modified DNA: A possible immunogenic stimulus for anti-DNA autoantibodies in systemic lupus erythematosus.

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.

Involvement of monoamines and proinflammatory cytokines in mediating the anti-stress effects of Panax quinquefolium.

Panax quinquefolium (PQ) is well acclaimed in literature for its effects on central and peripheral nervous system. The present study explores the effects of PQ on stress induced changes of corticosterone level in plasma, monoamines (NA, DA and 5-HT) and interleukin (IL-2 and IL-6) levels in cortex and hippocampus regions of brain and also indicate their possible roles in modulating stress. Mice subjected to chronic unpredictable stress (CUS, for 7 days) showed significant increase in plasma corticosterone level and depletion of noradrenaline (NA), dopamine (DA) and 5-hydroxytryptamine (5-HT) levels in cortex and hippocampal regions along with an increased level of IL-2 and IL-6 in the same areas. Aqueous suspension of PQ was administered daily at a dose of 100 and 200mg/kg p.o. prior to the stress regimen and its effects on selected stress markers in plasma and brain was evaluated. PQ at a dose of 200mg/kg p.o. was found to be effective in normalizing the CUS induced elevation of plasma corticosterone and IL-2, IL-6 levels in brain. Moreover, it was significantly effective in reinstating the CUS induced depletion of NA, DA and 5-HT in hippocampus, while NA and 5-HT in cortex of brain. However, PQ at a dose of 100mg/kg p.o. was found ineffective in regulating any of these CUS induced changes. Present study provides an insight into the possible role of PQ on hyperactive HPA axis in the regulation of immediate stress effectors like corticosterone, cytokines and brain monoamines. In this study, PQ has emerged as a potential therapeutic in the cure of stress related disorders and needs to be evaluated in clinical studies to ascertain its efficacy.