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Mohammad Bagher Khorrami,1,2 Hamid Reza Sadeghnia,3 Alireza Pasdar,1,4 Majid Ghayour-Mobarhan,5 Bamdad Riahi-Zanjani,6 Alireza Hashemzadeh,7 Mohammad Zare,2 Majid Darroudi8 1Department of Modern Sciences and Technologies, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; 2Social Security Organization, 17th Shahrivar Hospital, Mashhad, Iran; 3Division of Neurocognitive Sciences, Psychiatry and Behavioral Sciences Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; 4Division of Applied Medicine, Medical School, University of Aberdeen, Aberdeen, UK; 5Biochemistry of Nutrition Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; 6Medical Toxicology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; 7NanoBioEletrochemistry Research Center, Bam University of Medical Sciences, Bam, Iran; 8Nuclear Medicine Research Center, Mashhad University of Medical Sciences, Mashhad, Iran Purpose: The purpose of this study was to investigate the acute toxic potential of cerium oxide nanoparticles (CNPs) synthesized by pullulan in adult male Wistar rats. Patients and methods: Thirty male Wistar rats randomly were divided into five experimental groups of six animals each. The animals were received 50, 100, 200, and 400 mg/kg CNPs for 14 consecutive days. At the end of the experiment, the rats were euthanized and histopathological evaluation of the liver and renal tissues, as well ass, the markers of serum oxidative stress including thiobarbituric acid reactive substances, total sulfhydryl content, and antioxidant capacity (using ferric reducing/antioxidant power assay) were assessed. Hematological parameters and the activity of liver function enzymes were also measured. Results: The results of this study showed that CNPs caused no significant changes in the activity of liver enzymes, hepatic and renal histopathology and hematological parameters, while significantly improved serum redox status. Conclusion: Acute administration of pullulan-mediated CNPs is safe and possess antioxidant activity. Keywords: green synthesis, metal oxide, sol-gel, toxicology, radical scavenger

Background: Contamination of water by toxic chemicals has become commonly recognized as an environmental concern. Based on our clinical observation in Mashhad, northeastern Iran, many people might be at risk of exposure to high concentrations of toxic heavy metals in water. Because wastewater effluents as well as water wells have been commonly used for irrigation over the past decades, there has been some concern on the toxic metal exposure of crops and vegetables irrigated with the contaminated water. Objective: To measure the concentrations of mercury, lead, chromium, cadmium, arsenic and aluminium in irrigation water wells and wastewaters used for agriculture in Mashhad, northeastern Iran.Methods: 36 samples were taken from irrigation water wells and a wastewater refinery in North of Mashhad at four times—May 2008, March 2009, and June and July 2010. Atomic absorption spectrometry was used to measure the concentration of toxic metals. Graphite furnace was used for the measurement of lead, chromium, cadmium and aluminum. Mercury and arsenic concentrations were measured by mercury/hydride system. Results: Chromium, cadmium, lead and arsenic concentrations in the samples were within the standard range. The mean±SD concentration of mercury in irrigation wells (1.02±0.40 μg/L) exceeded the FAO maximum permissible levels. The aluminum concentration in irrigation water varied significantly from month to month (p=0.03). All wastewater samples contained high mercury concentrations (6.64±2.53 μg/L). Conclusion: For high mercury and aluminum concentrations, the water sources studied should not be used for agricultural use. Regular monitoring of the level of heavy metals in water and employing the necessary environmental interventions in this area are strongly recommended. INSET: TAKE-HOME MESSAGE. [ABSTRACT FROM AUTHOR]

Objectives: To assess whether the combination of scapular-focused training and mulligan mobilization (SFTMM) improves pain and proprioception compared to scapular-focused training (SFT) and a control group in female rock climbers with shoulder impingement syndrome (SIS)., Design: Three-arm randomized controlled trial (RCT)., Setting: Outpatient setting., Subjects: Individuals were randomly assigned to SFTMM, SFT alone, and control group., Interventions: 8 weeks of SFTMM and SFT., Main Measures: Outcome measures were pain and proprioception., Results: The results revealed significant differences in pain scores and proprioception among female rock climbers with SIS who participated in SFTMM, SFT, and a control group (F(2, 32) = 81.01, p = 0.001, η2 = 0.83 for pain scores; F(2, 32) = 178.2, p = 0.001, η2 = 0.91 for proprioception scores). Post-hoc tests via the Bonferroni test indicated that both SFTMM and SFT significantly reduced pain levels (p = 0.001) and improved proprioception levels (p = 0.001) compared with the control group. There was no significant difference in pain scores and proprioception between the SFTMM group and the SFT group (p > 0.05)., Conclusions: In conclusion, the study indicates that SFTMM significantly reduces pain and improves proprioception in female rock climbers with SIS, as shown by notable changes compared to the control group. However, no statistically significant difference was found between the SFTMM (combined intervention) and SFT alone. Therefore, while the incorporation of SFT and MM shows promise; further research is needed to fully understand its long-term benefits and clinical implications., Ethical Code Registration: The study was approved at Ethics., Research: ac.ir, code: IR.SSRC.REC.1402.170 on 2023-10-22., (© 2024. The Author(s).)

Objectives: Contamination of surface waters is a major health threat for all living creatures. Some types of blue-green algae that naturally occur in fresh water, are able to produce various toxins, like Microcystins (MCs). Microcystin-leucine arginine (MC-LR) produced by Microcystis aeruginosa is the most toxic and abundant isoforms of MCs, and it causes hepatotoxicity. The present article reviews preclinical experiments examined different treatments, including herbal derivatives, dietary supplements and drugs against MC-LR hepatotoxicity., Methods: We searched scientific databases Web of Science, Embase, Medline (PubMed), Scopus, and Google Scholar using relevant keywords to find suitable studies until November 2023., Results: MC-LR through Organic anion transporting polypeptide superfamily transporters (OATPs) penetrates and accumulates in hepatocytes, and it inhibits protein phosphatases (PP1 and PP2A). Consequently, MC-LR disturbs many signaling pathways and induces oxidative stress thus damages cellular macromolecules. Some protective agents, especially plants rich in flavonoids, and natural supplements, as well as chemoprotectants were shown to diminish MC-LR hepatotoxicity., Conclusion: The reviewed agents through blocking the OATP transporters (nontoxic nostocyclopeptide-M1, captopril, and naringin), then inhibition of MC-LR uptake (naringin, rifampin, cyclosporin-A, silymarin and captopril), and finally at restoration of PPAse activity (silybin, quercetin, morin, naringin, rifampin, captopril, azo dyes) exert hepatoprotective effect against MC-LR., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Fusarium head blight (FHB) is a devastating fungal disease affecting different cereals, particularly wheat, and poses a serious threat to global wheat production. Chitinases and β-glucanases are two important proteins involved in lysing fungal cell walls by targeting essential macromolecular components, including chitin and β-glucan micro fibrils. In our experiment, a transgenic wheat (Triticum aestivum) was generated by introducing chitinase and glucanase genes using Biolistic technique and Recombinant pBI121 plasmid (pBI-ChiGlu (-)). This plasmid contained chitinase and glucanase genes as well as nptII gene as a selectable marker. The expression of chitinase and glucanase was individually controlled by CaMV35S promoter and Nos terminator. Immature embryo explants from five Iranian cultivars (Arta, Moghan, Sisun, Gascogen and A-Line) were excised from seeds and cultured on callus induction medium to generate embryonic calluses. Embryogenic calluses with light cream color and brittle texture were selected and bombarded using gold nanoparticles coated with the recombinant pBI-ChiGlu plasmid. Bombarded calluses initially were transferred to selective callus induction medium, and later, they were transfferd to selective regeneration medium. The selective agent was kanamycin at a concentration of 25 mg/l in both media. Among five studied cultivars, A-Line showed the highest transformation percentage (4.8%), followed by the Sisun, Gascogen and Arta in descending order. PCR and Southern blot analysis confirmed the integration of genes into the genome of wheat cultivars. Furthermore, in an in-vitro assay, the growth of Fusarium graminearum was significantly inhibited by using 200 μg of leaf protein extract from transgenic plants. According to our results, the transgenic plants (T 1 ) showed the resistance against Fusarium when were compared to the non-transgenic plants. All transgenic plants showed normal fertility and no abnormal response was observed in their growth and development., (© 2024. The Author(s).)

Introduction: Tarragon, with the scientific name of Artemisia dracunculus , is a perennial herbaceous plant with a wide spectrum of pharmacologic properties. In the current investigation, BALB/c mice were used to examine the immunomodulatory effects of hydroalcoholic extract of tarragon (HET)., Methods: Mice were treated with hydroalcoholic extract of Artimisia dracunculus (HET) at two doses (250 and 500 mg/kg) for 14 days. The host hematological parameters, spleen cellularity histopathology, hemagglutination titer assay (HA), delayed-type hypersensitivity (DTH) responses, IFN-γ and IL-4 levels produced by spelenocytes, and the proliferation of lymphocytes were assayed., Results: HET at a high dose significantly could increase the number of white blood cells and lymphocytes compared to the control group. The lymphocyte proliferation in exposure to PHA significantly increased in the HET group at both doses compared to the control group, whilst this index in the presence of LPS increased significantly for the 500 mg/kg-HET group only. Moreover, in the HA and DTH tests, HET significantly increased the proliferation of lymphocytes as compared with the control group. Furthermore, HET significantly increased the amount of IFN-γ parallel to a decrease in the level of IL-4 in compared to the control group., Conclusion: Based on our findings, HET has potent immunostimulant characteristics. More investigation into tarragon's potential to be used in the treatment of disorders caused by a weakened immune response should be conducted., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Maintenance of immune system integrity is a vital requirement to protect human body against pathogens/cancers. Natural compounds have long been used due to their benefits for the immune system. One of which is bee venom that contains a peptide called melittin having antimicrobial and anticancer effects. Since a limited number of studies regarding the effects of melittin on the immune system have been carried out, we aimed to evaluate the effects of melittin on BALB/c mice immune system parameters., Methods: Female BALB /c mice were treated intraperitoneally (i.p) with 0.75 and 1.5 mg/kg doses of melittin for 14 days (5 doses per week). The negative control group received i.p normal saline whereas the positive controls received i.p 20 mg/kg cyclophosphamide (CYP). Immunological parameters such as hematological parameters, delayed-type hypersensitivity (DTH), hemagglutination titer (HA), spleen cellularity, splenocytes proliferation, as well as spleen and bone marrow histopathological assessment were evaluated., Results: Our findings showed that melittin has no gross pathological effect on the spleen and bone marrow. It was also demonstrated that melittin has no any significant effect on hematological parameters. Melittin did not cause any significant changes to proliferation response of splenocytes to PHA and LPS, spleen cellularity, DTH response, as well as the production of anti-SRBC antibodies. According to our results, melittin at 0.75 and 1.5 mg/kg doses could not induce significant changes on immune parameters and as a result, melittin was found to be safe for the mice immune system., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Introduction: Hepatitis and acquired immunodeficiency are major health concerns in high-risk patients with renal failure undergoing hemodialysis. This might be due to the number of blood transfusions, age, and dialysis duration. We aimed to investigate the prevalence of HBV, HCV, and HIV in hemodialysis patients to determine the effectiveness of preventive measures already in place and the possible correlation between various risk factors and viral infection in the Hemodialysis Center in Mashhad, Iran., Methodology: Sixty-five patients were included in a retrospective cross-sectional study. The demographic information was collected. Hepatitis-B surface antigens, anti-HCV, and anti-HIV antibodies were screened using ELISA., Results: Out of 65 patients, 34 (52.3%) were male, and 31 (47.7%) were female. Mean duration of dialysis was 30.68 ± 26.39 months, and the mean age was 64.95 ± 14.09 years. We found 9 (13.8%) patients that were HBV positive (HbsAg-positive), and 3 (4.6%) patients were HCV positive. Sex and the number of blood transfusions were found to be risk factors for HBV infection and had statistical significance (p = 0.02 and p = 0.01, respectively). No statistical significance was found between HBV- and HCV- positivity and the mean age of patients (p = 0.84 and p = 0.76, respectively). All patients were HIV-negative., Conclusions: Prevalence of HBV was high and significant. More preventive measures need to be developed, and further studies should be conducted to examine the effectiveness of these measures. Moreover, evaluating the prevalence rates of HBV, HCV, and HIV in other hospitals and dialysis centers in Mashhad is recommended to minimize viral infections. Initial HBV vaccination for patients that require hemodialysis is crucial., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2023 Mohammad-Bagher Khorrami, Arian Amali, Mahmood Sadeghi, Bamdad Riahi-Zanjani.)

Loop-mediated isothermal amplification is a promising candidate for the rapid detection of Mycobacterium tuberculosis . However, the high potential for carry-over contamination is the main obstacle to its routine use. Here, a closed tube LAMP was intended for the visual detection of Mtb to compare turbidimetric and two more favorable colorimetric methods using calcein and hydroxy naphthol blue (HNB). Additionally, a less studied dye (i.e., eriochrome black T (EBT)) was optimized in detail in the reaction for the first time. Mtb purified DNA and 30 clinical specimens were used to respectively determine the analytical and diagnostic sensitivities of each method. The turbidimetric method resulted in the best analytical sensitivity (100 fg DNA/reaction), diagnostic sensitivity and specificity (100%), and time-to-positivity of the test (15 min). However, this method is highly prone to subjective error in reading the results. Moreover, HNB-, calcein-, and EBT-LAMP could respectively detect 100 fg, 1 pg, and 1 pg DNA/reaction (the analytical sensitivities) in 30, 15, and 30 min, while the diagnostic sensitivity and specificity were respectively 93.3% and 100% for them all. Interestingly, EBT-LAMP showed the lowest potential for subjective error in reading the results. This report helps judiciously choose the most appropriate visual method, taking a step forward toward the field applicability of LAMP for the detection of Mtb, particularly in resource-limited settings.

Objective: Portulaca oleracea , commonly known as Purslane, is traditionally used as a sour, diuretic, and cooling herb with hemostatic properties. The present study evaluates the antianemic effect of methanolic and aqueous extracts of P. oleracea in a phenylhydrazine model of anemia., Materials and Methods: Phenylhydrazine (60 mg/kg/day, i.p., two consecutive days) was used to induce anemia in rats. The aqueous and methanolic extracts of P. oleracea were prepared, and three methods of treatment were defined with two doses (500 and 750 mg/kg, i.p.). The hematological parameters and blood cell morphology, total and direct bilirubin, and morphology, and pathology of bone marrow were evaluated., Results: The results showed that the methanolic extract has better effects than aqueous extract in improving phenylhydrazine-induced anemia. Our results showed that administration of 500 and 750 mg/kg of P. oleracea methanolic extracts for 4 days could protect against the development of anemia caused by phenylhydrazine., Conclusion: In summary, the methanolic extracts of P. oleracea might be effective in phenylhydrazine-induced anemia., Competing Interests: The authors have declared that there is no conflict of interest.

Background: Diazinon (DZN), a widely used chemical herbicide for controlling agricultural pests, is an important organophosphorus pesticide and an environmental pollutant which induces toxic effects on living organisms during long-term exposure. Thymoquinone (TQ) is a phytochemical bioactive compound with antioxidant and anti-inflammatory properties. We aimed to evaluate the protective effects of TQ against DZN-induced hepatotoxicity through alleviating oxidative stress and enhancing cholinesterase (ChE) enzyme activity., Methods: Rats were randomly divided into six groups (n = 8); a negative control group receiving corn oil; a group only receiving DZN (20 mg/kg/day); a group treated with TQ (10 mg/kg/day), and three treatment groups as TQ + DZN, receiving different doses of TQ (2.5, 5, and 10 mg/kg/day). All experimental animals were orally treated for 28 consecutive days. The levels of superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA), alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and lactic acid dehydrogenase (LDH) were determined. In addition, ChE activity and histopathological changes were evaluated., Results: The results showed that DZN decreased GSH level (p < 0.01) and SOD activity (p < 0.01) in parallel to an increase in MDA level (p < 0.01) and increased the activity of AST, ALT, ALP, and LDH (p < 0.01) in comparison to the negative control group. Our findings demonstrated that TQ administration could diminish hepatotoxicity and reduce oxidative damage in DZN-treated rats, which could be linked to its antioxidant and free radical scavenging properties. It was also observed that TQ 10 mg/kg remarkably increased the activity of acetylcholinesterase, butyrylcholinesterase, and SOD enzymes, elevated GSH, decreased MDA, and reduced pathological alternations of the liver induced by DZN., Conclusion: Thymoquinone 10 mg/kg increased the activity of plasma and blood cholinesterases and reduced DZN-induced alternations of the liver. Improvement of butyryl- and acetylcholinesterase activity suggests that maybe TQ supplement could be beneficial as pre-exposure prophylaxis among farm workers spraying pesticides., (© 2022. The Author(s).)

Purpose: Although Valproate (VPA) has several advantages in controlling seizures, it may cause serious hematological consequences. Hematotoxicity of VPA is particularly important in pediatrics because patients at this age are at a growing risk of leukemia. For a conclusive agreement about the toxicity of VPA, in this study, we systematically reviewed the literature in which the hematological consequences of VPA had been emphasized., Methods: A systematic literature search was performed in June 2021 on electronic databases to find original research on the association between VPA therapy and hematotoxicity in pediatric patients. For this purpose, the following search terms "hematotoxicity", "valproic acid" and "pediatrics" with different spellings and similar terms, were searched in the title, keywords, and abstracts of articles. The data were collected and used for qualitative data description., Results: A total of 36 relevant articles with an overall 1381 study population were included. The results showed that VPA could cause severe hematotoxicity in children even at therapeutic doses. Neutropenia, thrombocytopenia, and bone marrow depression are the most common complications associated with VPA therapy. Also, findings showed that after discontinuation of VPA and starting other antiepileptic drugs or reducing the administered VPA dose, hematologic damages were entirely resolved, and all the hematological parameters improved during two weeks., Conclusion: This review showed that VPA therapy could cause hematotoxicity in children; hence, it is recommended to monitor hematological indices during VPA therapy. Also, according to the suggested mechanistic pathways of VPA side effects, a combination of VPA with antioxidants may reduce hematological side effects., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The aim of this study was to better understand the response of ex vitro acclimatized plants grown to a set of mineral nutrient combinations based on Hoagland solution. To reach that, two computer-based tools were used: the design of experiments (DOE) and a hybrid artificial intelligence technology that combines artificial neural networks with fuzzy logic. DOE was employed to create a five-dimensional IV-design space by categorizing all macroelements and one microelement (copper) of Hoagland mineral solution, reducing the experimental design space from 243 (3 5 ) to 19 treatments. Typical growth parameters included hardening efficiency (Hard), newly formed shoot length (SL), total leaf number (TLN), leaf chlorophyll content (LCC), and leaf area (LA). Moreover, three physiological disorders, namely, leaf necrosis (LN), leaf spot (LS), and curled leaf (CL), were evaluated for each treatment (mineral formulation). All the growth parameters plus LN were successfully modeled using neuro-fuzzy logic with a high train set R 2 between experimental and predicted values (72.67 < R 2 < 98.79). The model deciphered new insights using different sets of "IF-THEN" rules, pinpointing the positive role of Mg 2+ and Ca 2+ to improve Hard, SL, TLN, and LA and alleviate LN but with opposite influences on LCC. On the contrary, TLN and LCC were negatively affected by the addition of NO 3 - into the media, while NH 4 + in complex interaction with Cu 2+ or Mg 2+ positively enhanced SL, TLN, LCC, and LA. In our opinion, the approach and results achieved in this work are extremely fruitful to understand the effect of Hoagland mineral nutrients on the healthy growth of ex vitro acclimatized plants, through identifying key factors, which favor growth and limit physiological abnormalities., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Maleki, Maleki Zanjani, Kohnehrouz, Landin and Gallego.)

We aimed to review the literature to find the specific effect of opioids on the activity of cholinesterase (ChE) enzyme which plays a substantial role in the functioning of cholinergic system. Literature search was performed by two independent reviewers in order to find relevant articles about the changes in the activity of ChE in mice or rat following opioid administration. Based on findings from literature review, opioid administration is able to induce cholinergic modulation via decreasing or increasing the activity of ChE enzyme. However, the degree of variation of ChE in various brain regions is different. No gender differences was reported in the effect of opioids on ChE activity. Although chronic opioid administration may decrease enzyme function, ChE activity might be unchanged following opioid withdrawal using naloxone or the development of tolerance. Opioid type affects whether or not naloxone can reverse the changes of ChE. Direct inhibitory action of morphine and the other opioid ligands believed responsible for the decrease in the ChE activity. Moreover, the potency of codeine to induce allosteric enhancement of acetylcholine receptor signaling might be involved in the cholinergic modulation of codeine and other opioids. Animal studies on rat and mice showed that opioids may change the activity of ChE. These changes can pertain an increase or decrease in enzyme activity; as there might be no change. The type of opioid used may have an effect on the cholinergic modulation. It is beneficial to conduct cross-sectional and cohort studies on addicted individuals, especially opium abusers, to find the precise association of opioids with alterations in human acetyl cholinesterase or butyrylcholinesterase. Simulation studies can also examine the structure-function relationships and provide important details to better understand the mechanism of action of opioid compounds on ChE activity. In addition, understanding how opioids impact ChE activity may help perform proper interventions for drug abstinence., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Solid-phase microextraction (SPME) is an analytical method for microextraction of analytes, in which the analytes bind to the sorbent on the surface of the SPME fiber. Many types of chemical agents are used as sorbent; however, many of these sorbents cause secondary contamination or are not cost-effective. Here, aqueous extract of Ferula gummosa was evaluated as potential source of sorbent for simultaneous microextraction of morphine and codeine. For this purpose, multiwalled carbon nanotubes were carboxylated with H2SO4/HNO3 (3:1) and then functionalized with aqueous extract of F. gummosa. Functionalization was confirmed by Fourier transform infrared and Raman spectroscopy measurements as well as scanning electron microscopy analysis. Porous polypropylene hollow fibers were filled with the functionalized carbon nanotubes (CNTs) and used for analyte extraction in urine sample at 40°C and pH 6 for 2 min. Reversed-phase high-performance liquid chromatography (RP-HPLC) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis showed that the fiber could preconcentrate 1 ng/mL of morphine and 0.75 ng/mL codeine in urine sample and was successfully used for 30 times with no significant loss in the extraction efficiency. Limit of detection (LOD) and limit of quantification (LOQ) for morphine were 1 and 3.3 ng/mL, respectively. LOD and LOQ for codeine were determined 0.75 and 2.47 ng/mL, respectively. Recovery of the fiber was 80% and 93% for morphine and codeine, respectively. SPME fiber using extract of F. gummosa plant was used for the detection of a small amount of morphine in urine sample. Therefore, plants can be considered as abundant and cheap sources of sorbent for various analytical purposes., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: While phenobarbital (PB) is commonly used for the management of seizures in newborns and pediatrics, its administration may accompany acute poisoning. We aimed to review the literature to find out the frequency of PB poisonings in newborns and children with seizures., Method: A literature search was performed by two independent reviewers to find relevant articles about PB toxicity in neonates and pediatrics that were treated for the seizure., Results: 18 articles met the inclusion criteria and were included in this systematic review. The main reasons for PB poisoning in studied patients were therapeutic intoxication. Reported signs of PB poisoning were lethargy, sedation, lack of sucking, fever, skin rash, hepatic inflammation and alopecia. Moreover, respiratory depression, encephalopathy, myocardial failure, syndrome of inappropriate antidiuretic hormone, and coma were among the complications of acute PB toxicity in children and infants., Conclusion: PB therapy for the management of seizures in newborns and children might be associated with poisoning. Although supportive and symptomatic treatments are available for PB overdose, it should be administered with caution, using drug monitoring to avoid toxicity., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Aflatoxin M 1 (AFM 1 ) is a 4-hydroxylated metabolite of aflatoxin B 1 (AFB 1 ). It induces various toxicological effects including immunotoxicity. In the present study, we investigated the effects of AFM 1 on immune system and its modulation by MicroRNA (miR)-155. AFM 1 was administered intraperitoneally at doses of 25 and 50 µg/kg for 28 days to Balb/c mice and different immune system parameters were analyzed. The levels of miR-155 and targeted proteins were evaluated in isolated T cells from spleens of mice. Spleen weight was reduced in mice exposed to AFM 1 compared to negative control. Proliferation of splenocytes in response to phytohemagglutinin-A was reduced in mice exposed to AFM 1 . IFN-γ was decreased in mice exposed to AFM 1 , whereas IL-10 was increased. Concentration of IL-4 did not change different in mice exposed to AFM 1 compared to negative control. Exposure to AFM 1 reduced the expression of miR-155. Significant upregulation of phosphatidylinositol-3, 4, 5-trisphosphate 5-phosphatase 1 (Ship1) and suppressor of cytokine signaling 1 (Socs1) was observed in isolated T cells from spleens of mice treated with AFM 1, but the transcription factor Maf (c-MAF) was not affected. These results suggest that miR-155 and targeted proteins might be involved in the immunotoxicity observed in mice exposed to AFM 1 .

The high toxicity of cadmium (Cd) and its ready uptake by plants has become a major agricultural problem. To investigate the genetic architecture and genetic regulation of Cd tolerance in barley, we conducted quantitative trait loci (QTL) analysis in the phenotypically polymorphic Oregon Wolfe Barley (OWB) mapping population, derived from a cross between Rec and Dom parental genotypes. Through evaluating the Cd tolerance of 87 available doubled haploid lines of the OWB mapping population at the seedling stage, one minor and one major QTL were detected on chromosomes 2H and 6H, respectively. For chlorosis and necrosis traits, the major QTL explained 47.24% and 38.59% of the phenotypic variance, respectively. RNA-Seq analysis of the parental seedlings under Cd treatment revealed 542 differentially expressed genes between Cd-tolerant Rec and Cd-susceptible Dom genotypes. By analyzing sequence variations in transcribed sequences of the parental genotypes, 155,654 SNPs and 1,525 InDels were identified between the two contrasting genotypes and may contribute to Cd tolerance. Finally, by integrating the data from the identified QTLs and RNA-Seq analysis, 16 Cd tolerance-related candidate genes were detected, nine of which were metal ion transporters. These results provide promising candidate genes for further gene cloning and improving Cd tolerance in barley., Competing Interests: The authors have declared that no competing interests exist.

Due to nutritional facts of milk in human life, the quality assessment of dairy products is of the utmost importance. The aim of the current study was to determine the 17β-estradiol level in commercial pasteurized and sterilized milk brands in Mashhad, Iran. In this regard, 160 samples including 80 pasteurized (40 high-fat and 40 low-fat) and 80 sterilized milk (40 high-fat and 40 low-fat) of widely used brands from different supermarkets were collected. The mean level of 17β-estradiol was 8.2 ± 0.59 pg/ml. The mean amount of estradiol was found to be 7.6 ± 0.47, 7.9 ± 0.45, 8.6 ± 0.63, and 8.9 ± 0.54 pg/ml for the low-fat pasteurized, low-fat sterilized, high-fat pasteurized and high-fat sterilized milk, respectively. There was no significant difference between the amount of estradiol in pasteurized and sterilized milk. As expected, the level of estradiol was statistically higher in high fat milks than that of low-fat milks. Considering the levels of 17β-estradiol measured here and the maximum permissible daily level of external estradiol entered to body through edible products recommended by EU and CAC (3.5 µg), at least in the short term, there will be no remarkable impact on the endocrine system. However, judging the long-term effects of using these products is not easy and simple at all, as cancers develop during a long period of time and has a multifactorial etiology., Competing Interests: Conflict of interestThe authors declare that there are no conflicts of interest., (© Association of Food Scientists & Technologists (India) 2019.)

Background: Sulfur mustard (SM) is a powerful blistering chemical warfare agent that has genotoxic effects. Cells with excessive proliferation such as lymphocytes may inherit this cellular toxicity which can lead to their malfunctions in the long-term. This study was designed to evaluate the status of acquired immunity among SM poisoned veterans around three decades after exposure., Methods: Thirty five male Iranian veterans having at least 25% disability due to SM poisoning with long-term complications in the respiratory system, skin or eyes were investigated. Non-functional/functional tests including hematological parameters, immunostaining analysis, lymphocyte proliferation assay, cytokine profile, and levels of total serum IgM, IgG and IgA were performed., Results: The results showed that most of the parameters of adaptive immune system of the veterans were currently within the normal ranges. However, changes in the proliferation index (PI) of lymphocytes showed problems with the lymphocytes which cannot be proliferated appropriately. PI values for PBMCs (peripheral blood mononuclear cells) in presence of PHA (Phytohemagglutinin-A) and LPS (lipopolysaccharide) mitogens were 1.16 ± 0.14 and 1.13 ± 0.07, respectively which are less than expected., Conclusions: Based on the results gathered in this study, most of the parameters of acquired immunity were normal. However, the observed failure of lymphocyte functions may disrupt physiological activity of whole immune system leading to long-term complications; including recurrent respiratory tract infections. Indeed, further cellular and molecular studies with regard to lymphocytes function are required to better understand the status of adaptive immunity in these patients. Graphical abstract ᅟ.

The ability of extraction and preconcentration of small quantities of substances from biological samples is important in analytical sciences, particularly forensic medicine. In the present study, we evaluated the binding potential of amino acids to produce a new solid phase microextraction fiber based on carbon nanotube (CNTs) for extraction and preconcentration of small amount of morphine in urine sample. Raw CNTs were first carboxylated and then functionalized with 3 amino acids including glutamate, arginine, and cysteine. Functionalization was confirmed by FTIR analysis, Raman spectroscopy and SEM imaging. The functionalized CNTs were coated on polypropylene hollow fiber and used for preconcentration. The results of HPLC analysis in isocratic elution mode using acetonitrile-sodium acetate (10:90, v/v; pH 4; 0.01 M) as the mobile phase showed that amino acids are able to adsorb morphine and the prepared fiber could preconcentrate a very low concentration of morphine (0.25 ppb) in urine matrix. In addition, the fiber was successfully used for up to 30 times with no significant loss in the extraction efficiency. Lowest limit of detection (LOD) and limit of quantitation (LOQ) was 0.07 and 0.25, respectively. Also, the lowest and best recovery of the fiber was 87.8% and 139% at LOQ, which belonged to glutamate and arginine, respectively. The fibers based on amino acids can be used for the detection of a small amount of morphine in biological samples, which are not detectable by conventional methods. Simple mechanism of these fibers in preconcentrating morphine makes them a novel candidate for detection of other opiates and drugs of abuses in crime scene investigations and postmortem examinations several days after exposure., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Antimicrobial peptides (AMPs) are best known for their bactericidal properties; however, due to their unique and flexible structures, they have also been proposed as potential selective sorbents for specific molecules. In the present study, we aimed to design and produce a new peptide-based microextraction fiber for preconcentrating morphine in urine samples. The binding of morphine to the peptide was first evaluated by computational simulation using the Molecular Operating Environment (MOE) 2015.10 software. A similar study was then performed using DS BIOVIA Materials Studio 2017 v17.1.0.48, which confirmed the results of the simulation carried out with MOE. Afterwards, those results were also confirmed by experimental research. In the experimental evaluation, carbon nanotubes (CNTs) were initially carboxylated with H 2 SO 4 /HNO 3 (3:1) and then functionalized with the peptide. FTIR analysis, Raman measurements, and SEM imaging were used to confirm that CNT functionalization was successful as well as to check the nanostructure of the fiber. To evaluate the functionality of the fiber, it was inserted into a microtube containing a urine sample that included morphine and then sonicated for 5 min at 40 °C. Afterwards, the fiber was washed with methanol 20% (H 2 O/methanol) and the resulting sample was analyzed by HPLC. This procedure was repeated for different concentrations of morphine in the urine sample. The computational and experimental results showed that a morphine concentration as low as 0.25 ppb in urine could be adsorbed and detected using the peptide fiber. Therefore, given its semi-selective binding affinity for morphine, this peptide-based fiber can be considered a new approach to the detection of small amounts of morphine in biological samples.

Chemical composition, antibacterial, antioxidant and cytotoxic activities of (Pistacia khinjuk) hull essential oil (EO) were evaluated in this study. The EO was isolated and analyzed by gas chromatography-mass spectrometry. The minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) were determined using 6 strains of Gram-positive and negative bacteria. DPPH radical scavenging (DPPH) and β-Caroten Bleaching (BCB) assays were used to measure antioxidant activity of the EO. In vitro cytotoxic activity was measured using MTT assay. Fifty-six compounds representing 99.5% of the total oil composition were identified. In the antibacterial results, Staphylococcus aureus was found to be the most susceptible strain (MIC and MBC = 16 μg/ml). Antioxidant IC 50 values were respectively 19.03 ± 0.001 and 49.22 ± 0.005 μg/mL. The IC 50 indexes of cytotoxic tests were 29.6, 37.3 and 41.1 μg/mL for MCF-7, PC3 and DU-145 cell lines, respectively., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Sulphur mustard (SM) is an incapacitating chemical warfare agent which causes acute and chronic toxicities in different body organs of affected individuals. The aim of this study was to investigate the innate immune status of the Iranian veterans who were exposed to SM around 30 years earlier and had more than 25% disabilities. In this regard, most functional and non-functional parameters of innate immunity were evaluated in 35 veterans. Phagocytic activity, nitroblue tetrazolium (NBT) reduction assay and haemolytic complement activity (HCA) in addition to routine haematological parameters, serum protein electrophoresis, complements C3 and C4 levels were studied. Measures of haematological parameters, serum proteins, C3 and C4 were almost within the normal range. Functional experiments such as phagocytic activity, NBT reduction assay and HCA were normal as well. However, serum protein analysis revealed a fair decrease in percentages of α 1 -globulin. Mean values of the parameters of innate immune system of the veterans three decades after SM poisoning were almost within the upper and lower normal limits. Reduced α 1 -globulin - maybe subsequent to a chain of SM-induced genetic disorders - may have been the result of α 1 -antitrypsin deficiency which may result in prevalent respiratory complications among these veterans. As a supplementary study, measurement of serum α 1 -antitrypsin in SM-poisoned veterans could be beneficial. Further studies are required to prove this hypothesis. Further investigations on the evaluation of the acquired immunity parameters as the second line of defence may reveal a better understanding of SM veterans' immune system status., (© 2018 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

Silymarin is a flavonoid complex extracted from the Silybum marianum plant with a wide range of pharmacological and biochemical effects. In the present study, the immunomodulatory effects of silymarin were investigated in BALB/c mice. Silymarin was administered daily by intraperitoneal injection at doses of 50, 100 and 150 mg/kg for 14 consecutive days. Following the exposure, host hematological parameters, spleen cellularity and histopathological examination, as well as delayed-type hypersensitivity (DTH) responses, hemagglutination titers (HA), splenocyte cytokine production and lymphocyte proliferation assay were studied in all of the test groups of animals. The results showed that the low dose of silymarin (50 mg/kg) could stimulate both cellular and humoral immune functions in the treated hosts. In addition, silymarin at 100 mg/kg appeared to impact on DTH responses and lymphoproliferation. Based on the finding here, it would seem that silymarin has efficient immunostimulant properties. As a recommendation, the application of silymarin along with acupuncture technique (herbal acupuncture) can be thought as a good plan to modulate and enhance the immune system for the management of several immunodeficiency disorders. However, further studies are required to demonstrate this hypothesis., Competing Interests: Conflict of interest The authors declare that there are no conflicts of interest.

Background: For many years, medicinal plants and herbal therapy have been widely used in different societies for the treatment of various diseases. Besides their therapeutic potency, some of the medicinal plants have strong toxicity in human, especially in children and elderly. Despite common beliefs that natural products are safe, there have been few reports on their toxicities., Materials and Methods: In the present study, we aimed to systematically review the literature wherein acute plant poisoning and herbal intoxication have been reported in pediatric patients. After literature search and selection of the appropriate documents, the desired data were extracted and described qualitatively., Results: A total of 127 articles with overall 1453 intoxicated cases were collected. The results of this study showed that some medicinal plants can cause acute poisoning and complications such as hepatic and renal failure in children., Conclusion: The findings of this survey showed that acute plant poisoning can be life?threatening in children, and since a single?ingested dose of toxic plants can cause acute poisoning, parents should be aware of these toxic effects and compare the side effects of self?medication with its potential benefits., Competing Interests: There are no conflicts of interest.

Objectives: Radiation is one of the most important sources of free radical (such as reactive oxygen species) production, which plays an essential role in the etiology of over hundred diseases. The aim of the study was to investigate some immune parameters and hematological indices in healthy workers of the Radiology Department, University Hospital of Mashhad, Iran., Methods: The study was performed on 50 healthy workers: 30 radiology staff as the case group and 20 laboratory workers as the control group. The radiation dose received by the radiology staff participating in the study was less than the annual maximum permissible level, 50 millisievert. Hematological parameters, lymphocyte proliferation and cytokine production were studied in both groups., Results: Among healthy radiology workers, the hematological indices did not differ statistically; however, their proliferation indices and IFN- γ levels showed significant increases in parallel with decreases in the IL-4 levels as compared to controls. The immune system of workers exposed to low-dose ionizing radiation was found to be shifted from a Type 2 to a Type 1 response to promote cellular immunity., Conclusion: Based on our data, exposure to low-dose ionizing radiation may decrease the prevalence, frequency, and recurrence of various cancers and infectious diseases because of an increase in Th1-cell-based response, thus leading to more protection of the human body against tumor cells and foreign agents and possibly increased longevity. However, due to high rate of fluoroscopy use for interventional radiology, we suggest continuing research projects on radiation protection and hazards to prevent irreversible damage. As a recommendation, in future studies, radiology staff with a weakened immunity due to high radiation exposure should be considered as good choices to be treated using acupuncture techniques because acupuncture has been demonstrated to enhance the function and the number of immune cells., Competing Interests: Conflict of interest The authors declare that there are no conflicts of interest.

The effects of isoquinoline alkaloid berberine (BER) on spleen tissue CD4 + CD25 + Foxp3 + regulatory T (T reg ) cells were evaluated in BALB/c mice. Here, BER was administered daily by intraperitoneal injection at doses of 5 mg/kg and 10 mg/kg for 14 days. Following the exposure, mice spleen cellularities, IL-10 production by splenocytes, and spleen T reg /CD4 + cell profiles were studied in all the test groups of animals. The results showed that a high dose of BER (10 mg/kg) could decrease both the absolute and relative percentages of spleen T reg cells as well as decrease the production of IL-10 by splenocytes in the treated mice (p<0.05). BER at 5 mg/kg did not appear to affect any of these parameters. Based on the finding here, it would seem that BER has effective immunostimulatory properties, which contradicts the results from other studies indicating immunosuppressive effects of BER. Depending on the doses of BER used, it might have a broad spectrum from immunosuppressive to stimulatory effects. Further studies, including more doses, are required to better evaluate the effects of this natural product. Mechanistic studies are required, particularly in case of redox state of the immune cells, to elucidate and determine how BER functions to impart the toxicity effects demonstrated here and in other studies., (Copyright © 2017 Medical Association of Pharmacopuncture Institute. Published by Elsevier B.V. All rights reserved.)

Air pollution is a major concern of new civilized world, which has a serious toxicological impact on human health and the environment. It has a number of different emission sources, but motor vehicles and industrial processes contribute the major part of air pollution. According to the World Health Organization, six major air pollutants include particle pollution, ground-level ozone, carbon monoxide, sulfur oxides, nitrogen oxides, and lead. Long and short term exposure to air suspended toxicants has a different toxicological impact on human including respiratory and cardiovascular diseases, neuropsychiatric complications, the eyes irritation, skin diseases, and long-term chronic diseases such as cancer. Several reports have revealed the direct association between exposure to the poor air quality and increasing rate of morbidity and mortality mostly due to cardiovascular and respiratory diseases. Air pollution is considered as the major environmental risk factor in the incidence and progression of some diseases such as asthma, lung cancer, ventricular hypertrophy, Alzheimer's and Parkinson's diseases, psychological complications, autism, retinopathy, fetal growth, and low birth weight. In this review article, we aimed to discuss toxicology of major air pollutants, sources of emission, and their impact on human health. We have also proposed practical measures to reduce air pollution in Iran.

The frequency and levels of aflatoxin M1 (AFM1) in pasteurized milk samples in Sari, located in Mazandaran province, Iran, were determined by enzyme immunoassay. Seventy-six samples of pasteurized milk from different retail stores were randomly collected over four seasons during the year 2015. AFM1 contamination was detected in all milk samples. The mean concentration of aflatoxin M1 was 65.8 ng/l, with a range of 11.7-106.6 ng/l. The highest AFM1 level was detected in milk samples collected during spring. Forty-six (60.53 %) samples had AFM1 levels that exceeded the maximum acceptable levels (50 ng/l) recommended by the European Union (EU). Comparison of these results with previously published data for AFM1 in milk in Iran shows that the percentage of samples exceeding the EU maximum level is consistently high over the years, indicating a general problem related to AFB1 contamination in dairy feedingstuff.

The immunotoxic effects of the isoquinoline alkaloid berberine (BBR) were investigated in Balb/c mice. Here, BBR was administered daily by intraperitoneal injection at doses of 5 and 10 mg/kg for 14 days. Following the exposure, host spleen weight, cellularity and histopathology, as well as delayed-type hypersensitivity (DTH) responses, hemagglutination titers (HA), spleen cell subtype profiles, splenocyte cytokine production and lymphocyte proliferation were studied in all of the test groups of animals. The results showed that the high dose of BBR (10 mg/kg) could suppress both cellular and humoral immune functions in the treated hosts. BBR at 5 mg/kg only appeared to impact on DTH responses and lymphoproliferation. Based on the finding here, it would seem that BBR has effective immunosuppressive properties. Mechanistic studies are required to determine exactly how this material is acting to impart many of the immunotoxic effects demonstrated here. At the same time, further research should also be performed on BBR to further develop its potential use as an effective immunosuppressant or co-adjuvant for the treatment of diseases caused by an exaggerated or unwanted immune response.

Objectives: The aim of the present study was to investigate immunotoxic effect of safranal (SAF), a main component of Crocus sativus essential oil, using Balb/c mice., Materials and Methods: SAF was administered intraperitoneally at doses of 0.1, 0.5 and 1 ml/kg for 3 weeks. Hystopathological examination of spleen and bone marrow, cellularity of spleen, delayed type of hypersensitivity (DTH) response, hemagglutination titer (HA), cytokine production and lymphocyte proliferation assay were studied in various groups of animals., Results: Spleen cellularity for SAF groups (0.1 ml/kg SAF: 6.68 [± 0.88] × 10(7), 0.5 ml/kg SAF: 8.16 [± 1.33] × 10(7), 1 ml/kg SAF: 6.12 [± 0.59] × 10(7)) did not significantly differ as compared to vehicle control (8.52 [± 1.36] × 10(7); p > 0.05). In addition, SAF at all doses could not produce any significant changes in hematological parameters, HA titer, DTH and lymphoproliferation responses, as well as in release of cytokines by isolated splenocytes (p > 0.05). Despite a few studies demonstrating some immunomodulatory effects for saffron extract, SAF as a major constituent of saffron did not induce any marked effects in immune system parameters of mice., Conclusion: Contrary to the toxicological studies which have indicated that SAF is more toxic than other active constituents in saffron stigma, at least it was found to be safe to mice immune system and has no toxicity on humoral and cellular immune responses.

Agents that destroy tumor cells and simultaneously boost host anti-tumor immunity are of keen interest in cancer therapy. In the present study, the effect of carnosol on anti-tumor immunity in a Balb/c mouse model of fibrosarcoma was evaluated. Carnosol was administered intraperitoneally daily (at 5 or 10 mg/kg/day, for 7 days) to tumor-bearing mice (i.e. 7 days after initial injection of tumor cells). Another group of tumor-bearing mice was treated with 20 mg cyclophosphamide/kg/d (positive control); a final group received vehicle only (vehicle control). After an initial measure on Day 0, tumor size was measured twice during the 7-day treatment period. One day after the final treatment with vehicle/carnosol (i.e. Day 7), the mice had their tumors measured and then were euthanized to permit their spleen and tumor to be harvested for isolation of, respectively, splenocytes and tumor-associated lymphocytes. Using these materials, spontaneous and mitogen-induced release of interleukin (IL)-4, IL-10, and interferon (IFN)-γ, lymphocyte proliferation, and the absolute numbers/relative percentages of splenic and tumor-associated T-regulatory (Treg) and other T-lymphocyte sub-sets were evaluated. The results showed that carnosol at both doses significantly suppressed tumor growth and caused depletion of splenic and tumor-associated Treg cells. It also caused relative (vs control mouse cell values) decreases in splenocyte spontaneous/inducible production of IL-4 and IL-10 and increases in IFNγ and cell proliferation. Carnosol at either dose did not cause changes in the percentages of CD4(+) or CD8(+) lymphocytes in the spleen or in tumor-associated lymphocyte populations. The observed increases in IFNγ, decreases in IL-10 and IL-4 production, and reductions in splenic/tumor-associated Treg cell levels might be signs reflecting the potential anti-tumor activity of carnosol. Based on the findings here, it is asserted that carnosol is a likely candidate - after more complete toxicologic evaluation - for eventual use as an anti-cancer therapeutic.

Ursolic acid (UA) is plentifully present in fruits, foods, and medicinal plants, and has anti-cancer activity on many cancer cell lines. However, the effects of UA on some melanoma cells and the mechanisms of action have not been reported. The effect of UA on isolated human melanoma and fibroblast cell lines has been investigated using the MTT assay, and cell death was determined using Annexin-V/PI staining. To explore whether the activation of caspases was required for apoptosis induction, cells were treated with pan-caspase inhibitor and UA. Changes in apoptosis pattern were analyzed by flow cytometry. Activation of caspases was detected by western blot analysis. A significant concentration-dependent suppression of cell proliferation was seen after 24 and 48 h in the presence of UA. Apoptosis was considerably increased by UA, indicated by enhancement of an Annexin-V positive population and a sub-G1 peak. UA induced proteolytic processing of caspase-3. The results confirm the anti-cancer properties of UA on cultured human melanoma cells, possibly mediated through the induction of apoptosis following activation of caspases., (© 2014 International Federation for Cell Biology.)

Sulfur mustard (SM) is an incapacitating chemical warfare agent that was used against Iranian soldiers during the period from 1983 to 1988. We have investigated serum cytokines profiles of Khorasan veterans who were exposed to SM >23 years earlier. Forty-four male Iranian veterans who had >40% disabilities due to delayed complications of SM poisoning and had disabilities were investigated. A total of 30 healthy male volunteers (relatives of the veterans) were selected as the control group. Cytokine levels were measured in the serum of case and control subjects using commercial ELISA kits. Hematologic parameters (white/red blood cell counts, hemoglobin levels, immune cell differentials) were also performed on blood samples from the study subjects. The results indicated that serum levels of ICAM-1 were significantly higher in the samples from SM-exposed veterans (772.8 [± 15.1] ng/ml [p=0.014] vs. control values of 710.2 [± 20.0] ng/ml). On the other hand, serum IL-1β, IL-8 levels and TNFα, were significantly lower for the veterans than the controls (IL-1β: 3.8 [± 0.1] vs. 4.3 [± 0.2] pg/ml, p=0.037; IL-8: 21.0 [± 6.1] vs. 84.6 [± 20.3] pg/ml, p=0.002; TNFα: 4.5 [± 0.1] vs. 5.5 [± 0.1] pg/ml, p=0.027). Levels of other assayed cytokines, e.g., IL-2, -4, -5, -6, -10, and -12, IFNγ, TNFβ, and sVCAM-1 were not significantly different between the study populations. None of the assayed hematologic parameters appeared to differ as well. It seems possible that dysfunctions could have been induced in the innate immune functions of the SM-exposed veterans as a result of these changes in cytokine expression and that these, in turn, may have contributed to the increased incidence of a myriad of diseases that have been documented in these veterans, including cancers. Future studies must focus on examining the significance of these changes in circulating cytokines and their potential contribution to the development of different diseases in veterans exposed to SM., (Copyright © 2014 Elsevier Ltd. All rights reserved.)