A diet enriched with Pistacia atlantica fruits improves the female rats' reproductive system.

Background and aim: Baneh (Pistacia atlantica) is a plant species that is commonly consumed as food and has a long-standing traditional use as a sexual enhancer. Despite its widespread use, a limited amount of academic and scientific literature is available regarding its potential impact on the reproductive system. The present research aimed to study the effect of a diet enriched with Baneh on the female rats' reproductive system. Experimental procedure: Three groups of rats (n = 8) were subjected to the intended diet for six weeks. Subsequently, their histomorphometric parameters, sex hormone levels, as well as the expression of oxytocin (OXT) and oxytocin receptor (OXTR) genes were measured. The rats' serum vitamin D, zinc, and lipid profiles were also evaluated. Results and conclusion: Results revealed that compared to the normal food, the diet containing 20 % Baneh significantly increased the progesterone and estradiol levels three and two times, respectively. It decreased the total body weight while increasing the ratio of ovary weight to the body weight. Furthermore, the Baneh-enriched diet raised HDL, zinc, and vitamin D levels, though it reduced the LDL and TG levels by 15 µg/dl and 24 µg/dl, respectively, and the concentration of ovary malondialdehyde decreased by 50 % in the treated group. Also, the diet increased the follicle graph, corpus luteum, the thickness of the epithelium, the number of endometrial glands, and the expression of both OXT and OXTR genes. Our findings suggested that P. atlantica could considerably improve the female sex hormone levels and their reproductive system.

Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) +49A>G (rs231775) gene polymorphism is not associated with COVID-19 severity and mortality in an Iranian population.

Introduction: Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) regulates T cell immune responses as an immune activation inhibitor. Literature reviews suggest that COVID-19 is associated with dysregulation of the inflammatory immune response. The purpose of the present hospital-based case-control study was to evaluate the genetic association of the CTLA4 +49A > G (rs231775) Single Nucleotide Polymorphism (SNP) with COVID-19 severity and mortality among the Iranian people. Method: Genomic DNA of peripheral blood nuclear cells was extracted from the 794 COVID-19 patients and 167 control individuals. The polymorphic site of rs231775 was genotyped using the PCR-RFLP technique. Also, to identify whether this genetic variation was related to CTLA-4 mRNA expression, total RNA was extracted from 178 COVID-19 patients and 70 controls. The mRNA levels of CTLA-4 were determined using real-time PCR. Result: There were no statistically significant differences found in the genotype and allele frequencies among the different genetic models with regards to the severity and mortality of COVID-19. Furthermore, there was no significant association between rs231775 genotypes and CTLA-4 mRNA expression in patients. Conclusion: Our findings demonstrated that SARS-CoV-2 infection is not associated with rs231775 in the Iranian people. More investigations are crucial to show how this genetic variation affects other ethnic groups. Given the importance of CTLA-4 in regulating immune responses, further studies are recommended to examine other CTLA-4 SNPs and the function of this gene in COVID-19 patients.

Association of programmed cell death 1 (PD-1) gene polymorphism (rs10204525) with COVID-19 severity and mortality: A case-control study in the Iranian population.

BACKGROUND: Programmed cell death 1 (PD-1), as a negative immune regulator, regulates the activation of T cells and maintains the immune system's homeostasis. Previous studies suggest that the effective immune response against COVID-19 contributes to the outcome of the disease. The present study aims to evaluate whether the PD-1 rs10204525 polymorphism is associated with PDCD-1 expression and COVID-19 severity and mortality in the Iranian population. METHODS: The PD-1 rs10204525 was genotyped in 810 COVID-19 patients and 164 healthy individuals as a control group using Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Moreover, we assessed the expression of PDCD-1 in peripheral blood nuclear cells by real-time PCR. RESULTS: Regarding disease severity and mortality, no significant differences were detected between study groups in alleles and genotypes frequency distribution under different inheritance models. We found that the expression of PDCD-1 was significantly lower in COVID-19 patients with AG and GG genotypes than in the control group. Regarding disease severity, mRNA levels of PDCD-1 were significantly lower in moderate and critical patients carrying AG genotype than in control (P = 0.005 and P = 0.002, respectively) and mild (P = 0.014 and P = 0.005, respectively) individuals. Additionally, the severe and critical patients with GG genotype displayed a significantly lower level of PDCD-1 compared with the control (P = 0.002 and P < 0.001, respectively), mild (P = 0.004 and P < 0.001, respectively), and moderate (P = 0.014 and P < 0.001, respectively) ones. Regarding disease mortality, the expression of PDCD-1 was significantly lower in non-survivor COVID-19 patients with GG genotype than in survivors. CONCLUSION: Considering the lack of significant differences in PDCD-1 expression in different genotypes in the control group, lower expression of PDCD-1 in COVID-19 patients carrying the G allele suggests the impact of this single-nucleotide polymorphism on the transcriptional activity of PD-1.

A review of neurological side effects of COVID-19 vaccination.

Following the COVID-19 virus epidemic, extensive, coordinated international research has led to the rapid development of effective vaccines. Although vaccines are now considered the best way to achieve collective safety and control mortality, due to the critical situation, these vaccines have been issued the emergency use licenses and some of their potential subsequence side effects have been overlooked. At the same time, there are many reports of side effects after getting a COVID-19 vaccine. According to these reports, vaccination can have an adverse event, especially on nervous system. The most important and common complications are cerebrovascular disorders including cerebral venous sinus thrombosis, transient ischemic attack, intracerebral hemorrhage, ischemic stroke, and demyelinating disorders including transverse myelitis, first manifestation of MS, and neuromyelitis optica. These effects are often acute and transient, but they can be severe and even fatal in a few cases. Herein, we have provided a comprehensive review of documents reporting neurological side effects of COVID-19 vaccines in international databases from 2020 to 2022 and discussed neurological disorders possibly caused by vaccination.

Increased serum lipofuscin associated with leukocyte telomere shortening in veterans: a possible role for sulfur mustard exposure in delayed-onset accelerated cellular senescence.

BACKGROUND: Sulfur mustard (SM) is a toxic gas that causes chronic inflammation and oxidative stress leading to cell senescence. This study aimed to evaluate two indicators of biological aging (i.e., serum lipofuscin level and leukocyte telomere length) and assess their relationship based on the severity of SM exposure in the long term. METHODS: The study was performed on two groups of male participants. 1) SM-exposed group (exposed to SM once in 1987), 73 volunteers. 2) Non-exposed group, 16 healthy volunteers. The SM-exposed group was categorized into three subgroups based on the severity of SM exposure and body damage (asymptom, mild, and severe). The blood sample was prepared from members of each group. The serum lipofuscin, TGF-ß, malondialdehyde (MDA), c-reactive protein (CRP), and leukocyte telomere length (TL) were measured in all participants. RESULTS: The MDA level was increased in the SM-exposed group (mean = 39.6 µM, SD = 16.5) compared to the non-exposed group (mean = 21.1 µM, SD = 10.3) (P < 0.05). The CRP level was also increased in the SM-exposed group (mean = 5.12 mg/l, SD = 3.36) compared to the non-exposed group (mean = 3.51 mg/l, SD = 1.21), while the TGF-ß level was decreased (P < 0.05) in the SM-exposed group (mean = 52.6 pg/ml, SD = 18.7) compared to the non-exposed group (mean = 68.9 pg/ml, SD = 13.8). The relative TL was shorter in the SM-exposed group (mean = 0.40, SD = 0.28) than in the non-exposed group (mean = 2.25, SD = 1.41) (P < 0.05). The lipofuscin level was higher in the total SM-exposed group (mean = 1.44 ng/ml, SD = 0.685) than in the non-exposed group (mean = 0.88 ng/ml, SD = 0.449) (P < 0.05). The MDA and CRP levels were increased in the SM-exposed subgroups of asymptom, mild, and severe than the non-exposed group, while TGF-ß level and TL were decreased in those subgroups. The lipofuscin level was higher in the SM-exposed subgroups of mild and severe than in the non-exposed group. The regression analysis determined a negative correlation between lipofuscin level and TL. The lipofuscin/TL ratio was higher in the total SM-exposed group (mean = 6.36, SD = 5.342) than in the non-exposed group (mean = 0.51, SD=0.389). This ratio was also higher in the SM-exposed subgroups of asymptom, mild, and severe than in the non-exposed group. The lipofuscin/TL ratio did not differ between mild and severe subgroups. CONCLUSION: The delayed toxicity of SM is associated with chronic oxidative stress, continuous inflammatory stimulation, increased lipofuscin, and telomere shortening. Future studies are needed to verify the suitability of serum lipofuscin to telomere length ratio in determining the severity of SM toxicity.

The effects of P. atlantica as a libido booster and sexual enhancer on the reproductive system of male rats.

Background and aim: Alongside the advancement of various modern treatments, attention has recently been focused on finding alternative infertility treatments based on diet and herbal medicine. Pistacia atlantica (wild pistachio; Baneh) is a plant species traditionally known as a libido booster and sexual enhancer. Experimental procedure: The study aim was to evaluate the effects of a P. atlantica-enriched diet on the functions of the reproductive system of male rats. Results and conclusion: Results revealed that the diet containing 20% P. atlantica doubled testosterone levels in the treatment group compared to the control. It decreased the total bodyweight, while significantly increased the ratios of the seminal vesicles, testis, and epididymis to the bodyweight of rats. The sperm count in the treatment group was 4.8 × 106/mL, which was significantly more than the control group (4.2 × 106/mL). Furthermore, the utilization of P. atlantica significantly raised HDL levels, though it reduced the LDL and TG levels and the concentration of testis MDA. Concerning other factors, the 20% of P. atlantica considerably increased the serum level of Zinc and vitamin D. Histomorphometric analysis revealed that the diet increased the testicular capsule thickness, whereas it did not cause any significant change in the diameter of the seminiferous tubule, the number of Leydig cells, and Sertoli cells. Additionally, the repopulation index, tubular differentiation index, and spermiogenesis index increased in the treatment group. Molecular analysis showed that the prescribed diet increased the expression of both oxytocin (OXT) and its receptor (OXTR) genes, improving the reproductive system function.

Concomitant use of relative telomere length, biological health score and physical/social statuses in the biological aging evaluation of mustard-chemical veterans.

Sulfur mustard (SM) is a toxic gas that has been used as a chemical weapon in wars. After many years, SM-exposed people are still suffering from its side effects such as biological and premature aging. This study was aimed to evaluate biological aging rate via involving biological health scoring (BHS), relative telomere length (TL) and different physical/social variables i.e. marital and smoking statuses, body mass index, salary and educational levels. BHS was calculated according to measurement of 18 biomarkers related to function of four physiological systems (endocrine, inflammatory, cardiovascular and metabolic systems) and two organs (liver and kidney). The volunteers were 442 individuals exposed to SM gas in 1987 and 119 healthy individuals as non-exposed group. Each group was divided based on leukocyte relative TL (short, intermediate and long). Our data showed an inverse correlation between BHS and relative TL in two groups. The BHS was significantly higher in SM-exposed group than non-exposed group, especially in the participants with short and intermediate TL. The BHS had also a positive correlation with smoking and BMI parameters, and a negative correlation with salary and educational levels in the participants with shorter telomeres; and SM strengthened these correlations in the shorter telomeres. It is concluded that the higher BHS along with shorter relative TL that are indices for lower health quality and biological aging, could be used in the health evaluation of non- and SM-exposed people; and involving of BHS, TL and physical/social covariates could be useful to make this evaluation more accurate.

Maternal deprivation effect on morphine-induced CPP is related to changes in opioid receptors in selected rat brain regions (hippocampus, prefrontal cortex, and nucleus accumbens).

Early-life environmental conditions affect offspring's development. Maternal deprivation (MD) can induce persistent changes that give rise to neuropsychiatric diseases including substance abuse disorders. However, long-lasting mechanisms that determine vulnerability to drug addiction remain unknown. We hypothesized that MD could induce changes in Opioid system, HPA (hypothalamic-pituitary-adrenal) axis, and BDNF (brain-derived neurotrophic factor), so may be involved in the drug abuse in later life. Male offspring of Wistar rats (n = 8 per group) were subjected to 3 h of daily MD during postnatal days 1-14. In adulthood, morphine-induced CPP (conditioned place preference) was investigated using two doses of morphine (3 and 5 mg/kg). Serum corticosterone level was measured by ELISA method. The expression level of genes in selected brain regions (hippocampus, prefrontal cortex, and nucleus accumbens) was determined by qPCR (quantitative PCR). A greater morphine-induced CPP was observed in MD rats with 3 and 5 mg/kg morphine compared to controls. MD group had a higher corticosterone level. A significant decrease was observed in the expression of BDNF gene (in all of the selected brain regions) and GR (glucocorticoid receptor) gene (in the hippocampus and nucleus accumbens) in MD rats. Also, a significant increase in the expression of µ Opioid receptor (in all of the selected brain regions) and κ Opioid receptor (in the prefrontal cortex and nucleus accumbens) was observed in MD rats. Our results suggest that MD induces alterations in the HPA axis function, BDNF level, and Opioid receptors system that enhance vulnerability to morphine at adulthood.

Sulfur mustard and biological ageing: A multisystem biological health score approach as an extension of the allostatic load in Sardasht chemical veterans.

BACKGROUND: Mustard gas as a chemical weapon has been used in wars and its long-term side effects are substantial in the human body. This study was aimed to apply an extension of allostatic load, known as synthetic biological health score (BHS), including the wear-and-tear of four physiological systems (endocrine, inflammatory, cardiovascular and metabolic systems) and two organs (liver and kidney) to estimate biological aging caused by sulfur mustard (SM) gas poisoning. METHODS: The plasma samples were prepared from two following groups of people; 1) 446 individuals exposed to SM gas in 1987. 2) 115 healthy members, at the same range of age and residence, as the non-exposed group. These people were chosen from the same patients' families and have not had any exposure to SM or pulmonary dysfunction. To estimate BHS, 18 blood-derived biomarkers of the mentioned systems and organs were measured and the relative contribution of many social and body parameters across the age groups was explored. RESULTS: It was revealed, in BHS calculation, the cardiovascular system had the most effect. Also, in the SM group, BHS was significantly higher than in the control group. This feature has a positive correlation with physical parameter (BMI) and a negative correlation with social parameters (salary and educational levels). CONCLUSION: The multisystem BHS could be useful in the evaluation of biological aging due to SM exposure. Social (education, good-paying job) and physical (BMI) parameters could influence BHS and the higher BHS indicates the progress of biological aging due to mustard gas.

Antidiabetic Properties of Hydroalcoholic Leaf and Stem Extract of Levisticum officinale: An implication for α-amylase Inhibitory Activity of Extract Ingredients through Molecular Docking.

Levisticum officinale (Apiaceae) is a favorite food spice. Iranian folk medicine claims that it has a prominent antidyslipidemic property but this is not documented scientifically so far. This study evaluated antidyslipidemic and the other antidiabetic aspects of the stem and leaf hydroalcoholic extract of it (LOE). Regarding oral glucose tolerance test results, LOE (500 mg/kg) administration 30 min before glucose loading significantly decreased the blood glucose level (13%) at 90 min in male rats. Additionally, LOE treatment (500 mg/kg, orally, once a day) for 14 days significantly reduced the serum glucose level (24.97%) and markedly improved the lipid profile and the insulin, creatinine, alanine aminotransferase and aspartate aminotransferase serum levels in diabetic rats. Moreover, LOE effectively amended the impaired antioxidant status and ameliorated lipid peroxidation in the plasma and pancreas and liver tissues of diabetics. Also, 14 days LOE treatment, significantly decreased the renal sodium-glucose cotransporter 2 and facilitated glucose transporter 2 (GLUT2) mRNA levels and GLUT2 gene expression in the enterocytes of jejunum tissue in comparison with diabetic untreated rats. HPLC method revealed the presence of chlorogenic acid, rosmarinic acid, caffeic acid, quercetin and luteolin and GC-MS analysis detected bioactive compounds like phthalides, thymol, phytol, hexanoic acid, carene and menthofuran. LOE showed α-amylase (αΑ) inhibitory activity and in silico studies predicted that among extract ingredients luteolin, quercetin, rosmarinic, caffeic, and hexanoic acids have the greatest αΑ inhibition potecy. Thus, current results justify antidyslipidemic value of L. officinale and shed light on more antidiabetic health benefits of it.

Augmentation of morphine-conditioned place preference by food restriction is associated with alterations in the oxytocin/oxytocin receptor in rat models.

BACKGROUND: Studies indicate that food restriction (FR) reinforces the effects of morphine. The exact mechanisms by which FR influences the reward circuitry of morphine have not yet been determined. OBJECTIVES: We hypothesized that the effects of FR on the oxytocin (OXT) system and HPA axis can be associated with substance abuse disorders. In this study, the serum levels of OXT and corticosterone, and the expression of OXT/OXT receptor (OXTR), glucocorticoid receptor (GR), and brain-derived neurotrophic factor (BDNF) in the hippocampus, prefrontal cortex, and nucleus accumbens were investigated in an FR model. METHODS: First, the male rats (n = 8 per group) were subjected to FR for 3 weeks. Then, morphine-induced conditioned place preference (CPP) was observed using two doses of morphine (3 and 5 mg/kg). The serum concentrations of corticosterone and OXT were determined by ELISA and the expression of genes was examined by qPCR. RESULTS: FR induced an enhanced preference in the animals for the 5 mg/kg dose of morphine compared to the controls. Serum corticosterone levels increased after FR but OXT levels decreased. Meanwhile, FR actuated downregulation of GR, BDNF, and OXT genes, while inducing the overexpression of OXTR. CONCLUSION: We propose the inclusion of OXT and OXTR alterations in the enhancement of morphine-induced CPP and addiction vulnerability following FR. Moreover, we conclude that altered BDNF levels and HPA axis activity may be the mechanisms involved in the effects of FR on morphine-induced behavior.

Alteration in serum levels of immunoglobulins in seriously eye-injured long-term following sulfur-mustard exposure.

INTRODUCTION: Sulfur mustard (SM) is a potent toxic agent that cause local and systemic changes in the human body such as dysregulation of the immunological system. This gas affects different organs such as lungs, skin, eyes and the gastrointestinal tract. METHODS: 128 veterans with SM-induced eye injuries were examined and compared to 31 gender- and age-matched healthy controls. Serum levels of IgM, IgE, IgA, IgG, and IgG subclasses were measured using ELISA method. RESULTS: There was no significant difference in IgM level between two groups with abnormal and normal ocular conditions except for those having bulbar conjunctiva-limbal ischemia and bulbar conjunctiva-hyperemia abnormalities. There were not significant difference in IgA, IgE, and IgG levels between two groups with and without ocular problem also between study groups. IgG1 level in some ocular abnormalities were significantly lower than the healthy control groups. IgG2 level in SM-exposed participants with stromal abnormality was higher in the SM-exposed groups without this problem. IgG2 levels in the exposed group with some ocular problems were significantly increased compared with control. IgG3 level in all patients did not reveal any significant changes compared with the controls except the fundus abnormality. IgG4 level was not significantly different between two groups with normal and abnormal ocular conditions. Nonetheless, IgG4 level in the exposed participants with some ocular abnormalities significantly increased compared with the controls. CONCLUSION: The results showed SM exposure could alter immunoglobulins level compared with healthy controls and the changes of IgG2 and IgG1 levels were associated with some ocular problems.

SP-A and TLR4 localization in lung tissue of SM-exposed patients.

INTRODUCTION: Long-term pulmonary complications are one of the major long-term consequences of sulfur mustard (SM) exposure. Toll-like receptor 4 (TLR4) involves in the pathogenesis of several pulmonary disorders. Surfactant protein-A (SP-A) regulates LPS-induced TLR4 localization and activation responses. However, the intensity and significance of TLR4 and SP-A expression by lung cells in SM-exposed patients is not clear. METHODS: The gene expression of TLR4 (through real-time PCR) and TLR4 and SP-A positive cells and alveolar type II cells, as SP-A producers, (using IHC) were assessed in formalin fixed paraffin embedded (FFPE) specimens from SM-exposed (n = 17), and non-SM exposed individuals (n = 12). RESULTS: TLR4 gene expression did not change between study groups. However, its cell surface presentation was significantly reduced in SM-exposed patients and particularly in which with constrictive bronchiolitis compared with the control group (P < 0.001 and P = 0.002, respectively). Frequency of alveolar type II cells was lower in the case group rather than the control group while the number of SP-A positive cells did not alter. CONCLUSIONS: These findings suggest that reduced TLR4 cell surface presentation may have anti-inflammatory function and SP-A may have a critical role in regulation of inflammatory responses in SM-exposed patients. Further investigation on other possible mechanisms involved in TLR4 internalization maybe help to illustrate the modulatory or inflammatory activity of TLR4 in these patients.

Serum Concentration of Thyroid Hormones Long-Term after Sulfur Mustard Exposure.

BACKGROUND: Despite several reports on the clinical manifestations of sulfur mustard (SM) intoxication, there is no study on serum concentrations of thyroid hormones long-term after SM exposure. In this study, the changes in thyroid functioning parameters 20 yr after SM exposure were evaluated. METHODS: This study is a part of a larger historical cohort study conducted in 2007 following 20 years of the exposure to SM, called Sardasht-Iran cohort study (SICS). We (SICS) comprised an SM-exposed group from Sardasht City, West Azerbaijan Province, Iran (n=169 as hospitalized group and n=203 as non-hospitalized exposed group); and control participants were selected from Rabat, a town near Sardasht (n=126). Peripheral blood samples were taken in fasting state and then the sera were separated. T4, T3, TSH, antithyroglobulin (anti-Tg), and antithyroid peroxidase (anti-TPO) concentrations in the sera were measured by the ELISA method. RESULTS: The mean of T3 concentration was significantly higher in the exposed than control group (0.88 ± 0.26 nmol/L vs 0.8 ± 0.25 nmol/L, P<0.001). The levels of TSH, T4, and T3up were not significantly different between the exposed and control groups. Thyroglobulin level was significantly higher in the exposed non-hospitalized group (56.07 ± 140.22 µg/L vs 17.66 ± 41.49 µg/L, P=0.004), but the level of anti-Tg and anti-TPO showed no significant differences between the two groups. CONCLUSION: More studies are needed on the alterations in thyroid hormones, their gene expressions, and mechanisms involved in SM exposure to clarify the causes of these alterations.

The Association between ocular problems and Serum Testosterone, Prolactin and Thyroglobulin concentrations in Delayed phase of Sulfur Mustard exposure.

BACKGROUND AND OBJECTIVE: Aside from direct toxic effects, Sulfur Mustard (SM) induced serum hormone abnormalities may aggravate ocular complaints, including Ocular Surface Discomfort (OSD) (burning, itching, and redness), dry eye sensation, photophobia, blurred vision, foreign body sensation, and pain. The aim of the current study was to investigate the possible association of ocular complaints with serum hormone concentrations in chronic phase of Sulfur Mustard (SM) exposure. METHODS: As a part of Sardasht Iran Cohort Study (SICS), 372 SM-exposed patients and 128 non-exposed participants were enrolled. Ocular complaints and ocular surface biomicroscopic conditions and serum hormones were compared. RESULTS: The exposed with tearing group had significantly higher mean serum levels of testosterone and prolactin (ng/mL) than controls (5.75 vs. 4.75, P=0.031; 11.71 vs. 8.42, P=0.009). The exposed with OSD group had significantly higher mean serum levels of prolactin than controls (12.48 vs. 6.90, P=0.002). The exposed with photophobia group had significantly higher mean serum levels of testosterone than the matched exposed (6.25 vs. 5.65, P=0.013). The exposed with blurred vision group had significantly higher mean serum levels of Thyroglobulin (Tg) (ng/mL) than the matched exposed (65.73 vs. 32.6, P=0.003). CONCLUSION: Higher mean serum levels of testosterone (in exposed with tearing and photophobia) and prolactin (in exposed with tearing and OSD) may play protective roles against SM effects. Higher mean serum levels of Tg may deteriorate the tear film integrity and optical surface, which causes blurred vision. In the chronic phase of SM toxicity, some ocular surface problems are associated with alterations in the serum concentrations of testosterone, prolactin, and Tg.

Effects of oregano essential oil on brain TLR4 and TLR2 gene expression and depressive-like behavior in a rat model.

The aim of the present study was to evaluate the effects of oregano essential oil (OEO) on the hippocampus and prefrontal cortex TLR 2/4 gene expression and depressive like behavior induced by chronic unpredictable stress (CUS). Sucrose preference and forced swim tests were adopted to examine the antidepressant effect. Control (CON), OEO, CUS, and CUS + OEO groups were used. The OEO and CUS + OEO groups received OEO (0.2 mL/kg, i.p.), CON and CUS received saline (0.2 mL/kg, i.p.), and the positive drug groups of CUS rats received fluoxetine (10 mg/kg) and diazepam (3 mg/kg) once daily for 14 days. The expression of TLR 2/4 was determined using real time quantitative polymerase chain reaction with the SYBR green reporter dye. The compositions of the OEO were determined by gas chromatography-mass spectroscopy. The main constituents were thymol (20.72%), gamma-terpinene (8.83%), borneol (8.72%), cymene (6.83%), carvacrol (6.274%), alfa-terpinene (5.26%), and sabinene (4.92%). Administration of OEO significantly alleviated the depressive symptoms of CUS. A higher level of TLR2/4 mRNA was seen in the brain of CUS group (P < 0.05). The CUS-induced increases in the TLR2/4 levels were not reversed by OEO. According to the present study OEO may have the antidepressant-like activity but have no effect on the stress-induced TLR-2/4 upregulation.

Association of Sulfur Mustard-Induced Ocular Problems with Serum and Blood Biochemical Parameters Changes.

BACKGROUND & OBJECTIVE: Many biochemical features of sulfur mustard (SM) intoxication have remained unknown. So far, the direct association between biochemical parameter changes and ocular problems in patients exposed to SM is not evaluated. The current study aimed at evaluating the associations between the ocular findings in patients with SM intoxication and the changes of serum and blood biochemical parameters. METHODS: In the current study, 372 patients exposed to SM and 128 matched controls were compared concerning the association between their ocular problems and biochemical parameters. Ocular problems include photophobia, ocular surface discomfort (OSD), etc. Biochemical parameters include uric acid, creatinine (Cr), hematocrit (HCT), total, direct and indirect bilirubin, high-density lipoproteins (HDL), alanine aminotransferase (ALT), calcium (Ca), fasting blood sugar (FBS), mean corpuscular hemoglobin concentration (MCHC), etc. RESULTS: The SM-exposed group with photophobia, OSD, tearing, blurred vision, abnormal tear status, and slit-lamp findings had significantly higher mean serum and blood levels of uric acid, Cr, HCT, and total and indirect bilirubin than the controls. The SM-exposed group with photophobia, tearing, ocular pain, blurred vision, bulbar conjunctival and limbal abnormalities had significantly higher mean serum and blood levels of HDL, ALT, Ca, FBS, MCHC, and HDL, indirect and total bilirubin, compared to the control group. CONCLUSION: The association of photophobia with uric acid, OSD and tearing with Cr, photophobia with HDL, ocular pain with Ca, and blurred vision with FBS may be explained for their known ocular effects in the SM-exposed subjects. SM-induced biochemical changes may intensify the ocular problems induced by the direct effects of SM.

Association between Acne and Serum Pro-inflammatory Cytokines (IL-1α, IL-1ß, IL-1Ra, IL-6, IL-8, IL-12 and RANTES) in Mustard Gas-Exposed Patients: Sardasht-Iran Cohort Study.

BACKGROUND: Acne vulgaris is a very common chronic inflammatory disorder, yet its pathogenesis is not clearly understood. As part of the SICS, this study was conducted to evaluate the association between the incidence of acne vulgaris in SM-exposed subjects (20 years after the exposure) and serum levels of proinflammatory cytokines (IL-1α, IL-1ß, IL-1Ra, IL-6, IL-8, IL-12 and RANTES) in an attempt to better understand the pathogenesis of long-term skin disorders of these individuals. METHODS: Serum concentrations of cytokines (IL-1α, IL-1ß, IL-1Ra, IL-6, IL-8, IL-12 and RANTES) were measured using sandwich ELISA technique. RESULTS: The median of serum levels of IL-1ß, IL-8 and RANTES were significantly higher in the exposed patients with acne than those without acne (P = 0.05, 0.03 and 0.001 respectively). There was no significant difference in serum levels of IL-1α, IL-1Ra and IL-6 between the exposed subgroups. CONCLUSION: We found a positive association between serum levels of pro-inflammatory cytokines (IL-1ß, IL-8, IL-12 and RANTES) and acne among SM-exposed population.

Evaluation of Association Between the Serum Levels of MMP-9 and MMP-9/TIMPs With Soluble Forms of Selectins and Itching Induced by Sulfur Mustard.

BACKGROUND & OBJECTIVE: Pruritus is the most frequent chronic dermal complication of sulfur mustard (SM), which negatively influences the quality of life. Exact pathophysiology of SM-induced itching is unknown. The current study aimed at evaluating the possible association between SM-induced itching and the serum levels of matrix metalloproteinase (MMP)-9 and their endogenous inhibitors, and serum levels of soluble forms of selectins (sL-, sP-, and sE-selectins) as adhesion molecules involved in the development of different inflammatory reactions. METHODS: Serum levels of MMP-9, MMP-9/ tissue inhibitors of metalloproteinases (TIMPs), and selectins were measured by the enzyme-linked immunosorbent assay (ELISA), and compared between the groups (n=368) with and without itching, and matched control groups (n=126). RESULTS: Serum levels of MMP-9 were significantly higher in the SM exposed group with itching, compared with that of the group without itching (medians: 894 and 624 pg/mL respectively; P-value =0.034). There was no relationship between the serum levels of MMP-9/TIMP-1, MMP-9/TIMP-2, MMP-9/TIMP-4, and itching in the patients exposed to SM. Median serum levels of sE- and sL-selectins in the exposed group with itching were higher than those of the exposed group without itching. These differences were statistically insignificant (P-values =0.084 and 0.095, respectively). CONCLUSION: According to the results of the current study, the increased serum levels of MMP-9 and selectins 20 years after exposure may play role in the pathogenesis and persistence of SM-induced itching in the exposed individuals.

Association of chemokines and prolactin with cherry angioma in a sulfur mustard exposed population--Sardasht-Iran cohort study.

Exposure to SM leads to short and long term adverse effects on various organs including the skin. Cherry angioma is one of the late skin disorders in SM exposed individuals. The pathogenesis of abnormal angiogenesis in cherry angioma is not well known but the role of inflammatory mediators and certain hormones, including prolactin, in the regulation of angiogenesis in other diseases has been reported. Alterations in serum levels of prolactin and chemokines in SM-exposed victims and the impact on angiogenesis are indications of the role in SM-induced cherry angioma. As part of the SICS, this study seeks to evaluate the possible association of prolactin and chemokines in the emergence of SM-induced cherry angioma. The serum concentrations of prolactin, IL-8/CXCL8, RANTES/CCL5, MCP-1/CCL2, and fractalkine/CX3CL1 were titrated using sandwich ELISA technique. There was a significant difference in the level of prolactin between the exposed subgroups (with cherry angioma n=72; mean: 10.13) and without cherry angioma (n=268; mean: 13.13, p<0.0096). Median of the serum levels of CCL2 in the exposed patients with cherry angioma was significantly higher than exposed patients without cherry angioma (median=203.5 pg/ml and median=187.10 pg/ml respectively, p=0.035). There was no significant difference in the serum levels of IL-8, RANTES and CX3L1 between the exposed subgroups with cherry angioma and without cherry angioma. This finding serves as a basis for further research on the molecular mechanisms and pathways involved in the pathogenesis of cherry angioma and other related disorders.