Plasma metabolites analysis of patients with papillary thyroid cancer: A preliminary untargeted 1H NMR-based metabolomics.

Metabolomics plays a crucial role in identifying molecular biomarkers that can differentiate pathological conditions. In the case of thyroid cancer, it is essential to accurately diagnose malignancy from benignity to avoid unnecessary surgeries. The objective of this research was to apply untargeted NMR-based metabolomics in order to identify metabolic biomarkers that can distinguish between plasma samples of patients with papillary thyroid cancer (PTC) and multinodular goiter (MNG), as well as PTC and healthy individuals. The study included a cohort of 55 patients who were divided into three groups: PTC (n=20), MNG (n=16), and healthy (n=19). Plasma samples were collected from all participants and subjected to 1H NMR spectroscopy. Differential metabolites were identified using chemometric pattern recognition algorithms. The obtained metabolic profile had the potential to differentiate PTC from healthy plasma, but not from MNG. In patients diagnosed with PTC, a total of 18 compounds were discovered, revealing elevated levels of leucine, lysine, and 4-acetamidobutyric acid, while acetate, proline, acetoacetate, 3-hydroxybutyrate, glutamate, pyruvate, cystine, glutathione, asparagine, ethanolamine, histidine, tyrosine, myo-inositol, and glycerol along with a lipid compound were found to be lower in comparison to those of healthy individuals. According to the area under the curve (AUC) of the receiver operating characteristic curve, this particular profile exhibited an impressive capability of 85% to discern PTC from healthy subjects (AUC=0.853, sensitivity=78.95, specificity=84.21). The utilization of the 1H NMR-based metabolomics approach revealed considerable promise in the identification of PTC from healthy plasma specimens. The modifications noticed in the plasma metabolites have the potential to act as practical biomarkers that are non-invasive and could suggest transformations in the metabolic profile of thyroid tumors.

Evaluation of common protein biomarkers involved in the pathogenesis of respiratory diseases with proteomic methods: A systematic review.

AIM: Respiratory disease (RD) is one of the most common diseases characterized by lung dysfunction. Many diagnostic mechanisms have been used to identify the pathogenic agents of responsible for RD. Among these, proteomics emerges as a valuable diagnostic method for pinpointing the specific proteins involved in RD pathogenesis. Therefore, in this study, for the first time, we examined the protein markers involved in the pathogenesis of chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), asthma, bronchiolitis obliterans (BO), and chemical warfare victims exposed to mustard gas, using the proteomics method as a systematic study. MATERIALS AND METHODS: A systematic search was performed up to September 2023 on several databases, including PubMed, Scopus, ISI Web of Science, and Cochrane. In total, selected 4246 articles were for evaluation according to the criteria. Finally, 119 studies were selected for this systematic review. RESULTS: A total of 13,806 proteins were identified, 6471 in COPD, 1603 in Asthma, 5638 in IPF, three in BO, and 91 in mustard gas exposed victims. Alterations in the expression of these proteins were observed in the respective diseases. After evaluation, the results showed that 31 proteins were found to be shared among all five diseases. CONCLUSION: Although these 31 proteins regulate different factors and molecular pathways in all five diseases, they ultimately lead to the regulation of inflammatory pathways. In other words, the expression of some proteins in COPD and mustard-exposed patients increases inflammatory reactions, while in IPF, they cause lung fibrosis. Asthma, causes allergic reactions due to T-cell differentiation toward Th2.

A computational approach for the identification of key genes and biological pathways of chronic lung diseases: a systems biology approach.

BACKGROUND: Chronic lung diseases are characterized by impaired lung function. Given that many diseases have shared clinical symptoms and pathogenesis, identifying shared pathogenesis can help the design of preventive and therapeutic strategies. This study aimed to evaluate the proteins and pathways of chronic obstructive pulmonary disease (COPD), asthma, idiopathic pulmonary fibrosis (IPF), and mustard lung disease (MLD). METHODS AND RESULTS: After collecting the data and determining the gene list of each disease, gene expression changes were examined in comparison to healthy individuals. Protein-protein interaction (PPI) and pathway enrichment analysis were used to evaluate genes and shared pathways of the four diseases. There were 22 shared genes, including ACTB, AHSG, ALB, APO, A1, APO C3, FTH1, GAPDH, GC, GSTP1, HP, HSPB1, IGKC, KRT10, KRT9, LCN1, PSMA2, RBP4, 100A8, S100A9, TF, and UBE2N. The major biological pathways in which these genes are involved are inflammatory pathways. Some of these genes activate different pathways in each disease, leading to the induction or inhibition of inflammation. CONCLUSION: Identification of the genes and shared pathways of diseases can contribute to identifying pathogenesis pathways and designing preventive and therapeutic strategies.

Adherence to healthy dietary patterns and its association with physical fitness in military personnel.

INTRODUCTION: Poor nutritional status might impact in unintentional weight loss and decreased muscle mass and strength. The levels of physical fitness (PF) is a predictor of chronic diseases in future years. Also, evaluation of fitness is an essential factor for duty in occupations which are sensitive to time and emergency reaction. Since there is no literature that study the association between dietary patterns and the PF level in physically strenuous occupations, the aim of this study was to examine the relationship between dietary patterns and the PF level in military staffs. METHODS: This cross-sectional study was carried out in military zones of Iran. Typical dietary intakes were assessed by using a semi-quantitative food-frequency questionnaire. Mediterranean diet (MD) score and healthy diet indicator (HDI) score were calculated. PF tests were designed to test the muscular strength, endurance and cardiovascular respiratory fitness (CRF). RESULTS: Mean age of participants was 33.03±4.65 in the study. Referring to the performance in the PF tests, there was a correlation between tertiles of MD (OR 4.37, p=0.048) and HDI (OR 5.21, p=0.019) scores and suitable PF level in the crude and confounder adjusted models. Also, a negative relationship was found between body mass index and waist circumference with fitness score. CONCLUSIONS: We concluded that accompanying a medium or high adherence to a healthy dietary pattern will have an impact on good level of PF and will result in a better working power and long-term health consequences among physically strenuous occupations.

Visual diagnosis of COVID-19 disease based on serum metabolites using a paper-based electronic tongue.

This study aims to use a paper-based sensor array for point-of-care detection of COVID-19 diseases. Various chemical compounds such as nanoparticles, organic dyes and metal ion complexes were employed as sensing elements in the array fabrication, capturing the metabolites of human serum samples. The viral infection caused the type and concentration of serum compositions to change, resulting in different color responses for the infected and control samples. For this purpose, 118 serum samples of COVID-19 patients and non-COVID controls both men and women with the age range of 14-88 years were collected. The serum samples were initially subjected to the sensor, followed by monitoring the variation in the color of sensing elements for 5 min using a scanner. By taking into consideration the statistical information, this method was capable of discriminating COVID-19 patients and control samples with 83.0% accuracy. The variation of age did not influence the colorimetric patterns. The desirable correlation was observed between the sensor responses and viral load values calculated by the PCR test, proposing a rapid and facile way to estimate the disease severity. Compared to other rapid detection methods, the developed assay is cost-effective and user-friendly, allowing for screening COVID-19 diseases reliably.

Proteomics analysis of chronic skin injuries caused by mustard gas.

Sulfur mustard (SM) is an alkylating and forming chemical that was widely used by Iraqi forces during the Iran-Iraq wars. One of the target organs of SM is the skin. Understanding the mechanisms involved in the pathogenesis of SM may help better identify complications and find appropriate treatments. The current study collected ten SM-exposed patients with long-term skin complications and ten healthy individuals. Proteomics experiments were performed using the high-efficiency TMT10X method to evaluate the skin protein profile, and statistical bioinformatics methods were used to identify the differentially expressed proteins. One hundred twenty-nine proteins had different expressions between the two groups. Of these 129 proteins, 94 proteins had increased expression in veterans' skins, while the remaining 35 had decreased expression. The hub genes included RPS15, ACTN1, FLNA, HP, SDHC, and RPL29, and three modules were extracted from the PPI network analysis. Skin SM exposure can lead to oxidative stress, inflammation, apoptosis, and cell proliferation.

Tear proteomics analysis of patient suffered from delayed mustard gas keratopathy.

Understanding the molecular and cellular mechanisms involved in the pathogenesis of ocular injured induced by mustard gas can help better identify complications and discover appropriate therapies. This study aimed to analyze the proteomics of tears of chemical warfare victims with mustard gas ocular injuries and compare it with healthy individuals. In this case-control research, 10 mustard gas victims with long-term ocular difficulties (Chronic) were included in the patient group, while 10 healthy persons who were age and sex matched to the patients were included in the control group. Schirmer strips were used to collect the tears of the participants. Proteomics experiments were performed using the high-efficiency TMT10X method to evaluate the tear protein profile, and statistical bioinformatics methods were used to identify the differently expressed proteins. 24 proteins had different expressions between the two groups. Among these 24 proteins, 8 proteins had increased expression in veterans' tears, while the remaining 16 proteins had decreased expression. Reactome pathways were used to look at proteins with various expressions, and 13 proteins were found to be engaged in the immune system, 9 of which were effective in the innate immune system, and 5 proteins were effective in the complement cascade. Ocular mustard gas exposure may cause a compromised immune system on the eye's surface, exposing the cornea to external and endogenous infections, and eventually causing corneal opacity and reduced vision.

Screening of Altered Metabolites and Metabolic Pathways in Celiac Disease Using NMR Spectroscopy.

BACKGROUND: Celiac disease (CeD) is an autoimmune intestinal disorder caused by gluten protein consumption in genetically predisposed individuals. As biopsy sampling is an invasive procedure, finding novel noninvasive serological markers for screening of at-risk CeD population is a priority. Metabolomics is helpful in monitoring metabolite changes in body fluids and tissues. In the present study, we evaluated serum metabolite levels of CeD patients relative to healthy controls with the aim of introducing new biomarkers for population screening. METHOD: We compared the serum metabolic profile of CeD patients (n = 42) and healthy controls (n = 22) using NMR spectroscopy and multivariate analysis. RESULT: 25 metabolites were identified by serum metabolic profiling. Levels of 3-hydroxyisobutyric acid and isobutyrate showed significant differences in CeD patients' samples compared with healthy controls (p < 0.05). According to pathway analysis, our data demonstrated that changes in nine metabolic pathways were significantly disrupted/affected in patients with CeD. These enriched pathways are involved in aminoacyl-tRNA biosynthesis; primary bile acid biosynthesis; nitrogen metabolism; glutamine and glutamate metabolism; valine, leucine, and isoleucine biosynthesis and degradation; taurine and hypotaurine metabolism; glyoxylate and dicarboxylate metabolism; glycine, serine, and threonine metabolism; and arginine biosynthesis. CONCLUSION: In summary, our results demonstrated that changes in the serum level of 25 metabolites may be useful in distinguishing CeD patients from healthy controls, which have the potential to be considered candidate biomarkers of CeD.

Efficacy of phytosomal curcumin among patients with non-alcoholic fatty liver disease.

Scientists proposed that curcumin could be used for treatment of non-alcoholic fatty liver disease (NAFLD). In this article, we aimed to identify the effect of curcumin on NAFLD improvement. Fifty patients with NAFLD, were divided into two groups in this randomized, double-blind, and controlled clinical trial. Patients in the curcumin group received 250 mg/day of phytosomal curcumin, while those in the control group received 250 mg/day of placebo for duration of eight weeks. Anthropometric measurements and fasting blood samples were taken once at the baseline and once at the end of the study. Analysis was performed on 45 patients (curcumin group n = 22, placebo group n = 22). According to between groups analysis, curcumin significantly reduced the carboxymethyl lisine (CML) (148 ± 108 ng/mL vs 197 ± 101 ng/mL, P = 0.04), 8-hydroxy-2' -deoxyguanosine (8-OHdG) (46.9 ± 31.1 ng/mL vs 52.1 ± 43.1 ng/mL P = 0.03), liver enzymes (P < 0.001), weight (P < 0.001), waist circumference (P < 0.001), body fat percent (P < 0.01), and body mass index (BMI) (P < 0.01) in comparison with placebo. However, curcumin supplementation compared to placebo did not reduce soluble receptors for advanced glycation end products (sRAGE), hip circumference, waist/hip, and fat free mass by the end of the study. Our study indicated that phytosamal curcumin might be able to reduce the NAFLD progress by reducing the anthropometric measures, AGEs, and DNA damage. However, we need more studies with longer intervention duration, and larger sample size.

The effect of curcumin with piperine supplementation on pro-oxidant and antioxidant balance in patients with non-alcoholic fatty liver disease: a randomized, double-blind, placebo-controlled trial.

Background The main causes of the progression of non-alcoholic fatty liver disease (NAFLD) are enhanced levels of reactive oxygen species and lipid peroxidation products. Therefore, the usage of antioxidant agents for the prevention and remedy of this disorder was recommended. Curcumin is proposed to treat NAFLD due to its high antioxidative activity. The aim of this study was to examine the effect of curcumin with piperine supplementation on oxidative stress in subjects with NAFLD. Methods In this double-blind, placebo-controlled trial, 55 subjects were randomly divided into two groups (curcumin with piperine and placebo). The participants received administrations of curcumin (500 mg) in combination with piperine (5 mg) and placebo daily for 8 weeks. Oxidative stress was assessed by measuring serum pro-oxidant and antioxidant balance (PAB) assay before and after the intervention. Results The serum PAB values did not significantly change between the treatment group vs. age and gender-matched placebo group after 8 weeks of supplementation. Also, curcumin in combination with piperine did not show a significant decrease (p = 0.06) in PAB levels compared to baseline. Conclusions The present study demonstrated that a dose of curcumin, co-supplied with piperine might be less than a dose in which curcumin can significantly decrease PAB values in these patients.

A pilot study of the effect of phospholipid curcumin on serum metabolomic profile in patients with non-alcoholic fatty liver disease: a randomized, double-blind, placebo-controlled trial.

BACKGROUND/OBJECTIVES: Curcumin, a natural polyphenol compound in the spice turmeric, has been found to have potent anti-oxidative and anti-inflammatory activity. Curcumin may treat non-alcoholic fatty liver disease (NAFLD) through its beneficial effects on biomarkers of oxidative stress (OS) and inflammation, which are considered as two feature of this disease. However, the effects of curcumin on NAFLD have been remained poorly understood. This investigation evaluated the effects of administrating curcumin on metabolic status in NAFLD patients. SUBJECTS/METHODS: Fifty-eight NAFLD patients participated in a randomized, double-blind, placebo-controlled parallel design of study. The subjects were allocated randomly into two groups, which either received 250 mg phospholipid curcumin or placebo, one capsule per day for a period of 8 weeks. Fasting blood samples were taken from each subject at the start and end of the study period. Subsequently, metabolomics analysis was performed for serum samples using NMR. RESULTS: Compared with the placebo, supplementing phospholipid curcumin resulted in significant decreases in serum including 3- methyl-2-oxovaleric acid, 3-hydroxyisobutyrate, kynurenine, succinate, citrate, α-ketoglutarate, methylamine, trimethylamine, hippurate, indoxyl sulfate, chenodeoxycholic acid, taurocholic acid, and lithocholic acid. This profile of metabolic biomarkers could distinguish effectively NAFLD subjects who were treated with curcumin and placebo groups, achieving value of 0.99 for an area under receiver operating characteristic curve (AUC). CONCLUSIONS: Characterizing the serum metabolic profile of the patients with NAFLD at the end of the intervention using NMR-based metabolomics method indicated that the targets of curcumin treatment included some amino acids, TCA cycle, bile acids, and gut microbiota.

Application of metabolomics to preeclampsia diagnosis.

Preeclampsia is a multifactorial disorder defined by hypertension and increased urinary protein excretion during pregnancy. It is a significant cause of maternal and neonatal deaths worldwide. Despite various research efforts to clarify pathogenies of preeclampsia and predict this disease before beginning of symptoms, the pathogenesis of preeclampsia is unclear. Early prediction and diagnosis of women at risk of preeclampsia has not markedly improved. Therefore, the objective of this study was to perform a review on metabolomic articles assessing predictive and diagnostic biomarkers of preeclampsia. Four electronic databases including PubMed/Medline, Web of Science, Sciencedirect, and Scopus were searched to identify studies of preeclampsia in humans using metabolomics from inception to March 2018. Twenty-one articles in a variety of biological specimens and analytical platforms were included in the present review. Metabolite profiles may assist in the diagnosis of preeclampsia and discrimination of its subtypes. Lipids and their related metabolites were the most generally detected metabolites. Although metabolomic biomarkers of preeclampsia are not routinely used, this review suggests that metabolomics has the potential to be developed into a clinical tool for preeclampsia diagnosis and could contribute to an improved understanding of disease mechanisms. ABBREVIATIONS: PE: preeclampsia; sFlt-1: soluble FMS-like tyrosine kinase-1; PlGF: placental growth factor; GC-MS: gas chromatography-mass spectrometry; LC-MS: liquid chromatography-mass spectrometry; NMR: nuclear magnetic resonance spectroscopy; HMDB: human metabolome database; RCT: randomized control trial; e-PE: early-onset PE; l-PE: late-onset PE; PLS-DA: partial least-squares-discriminant analysis; CRL: crown-rump length; UtPI: uterine artery Doppler pulsatility index; BMI: body mass index; MAP: mean arterial pressure; OS: oxidative stress; PAPPA: plasma protein A; FTIR: Fourier transform infrared; BCAA: branched chain amino acids; Arg: arginine; NO: nitric oxide.

Effect of green tea on plasma leptin and ghrelin levels: A systematic review and meta-analysis of randomized controlled clinical trials.

OBJECTIVE: The purpose of this study was to conduct a meta-analysis of randomized controlled trials (RCTs) to assess the effect of green tea on serum leptin and ghrelin concentrations. METHODS: We searched PubMed, ISI Web of Science, Scopus, and Google scholar databases up to December 2016. The searches included RCTs conducted in human adults, and studies on the effect of green tea and green tea extract on serum leptin and ghrelin concentrations as outcome variables. Weighted mean differences (WMDs) and standard errors (SEs) of changes in serum ghrelin and leptin levels were calculated. The random effects model was used to derive the summary mean estimates with their corresponding SEs. RESULTS: Eleven RCTs were eligible to be included in the systematic review and the meta-analysis. Our analysis indicated that green tea did not significantly affect leptin and ghrelin concentrations in comparison to placebo (WMD = 1.28 ng/mL, 95% confidence interval: -0.49 to 3.05; P = 0.156, and WMD = 21.49 pg/mL, 95% confidence interval: -40.86 to 83.84; P = 0.499, respectively). However, green tea was associated with an increase in leptin concentration in studies that lasted for more than 12 wk and an increase in ghrelin in women and non-Asians. CONCLUSIONS: Green tea or green tea extract might not be able to change circulatory leptin and ghrelin levels, especially with short-term interventions. More RCTs with longer duration of treatment and higher doses are necessary to assess green tea's effect on fat mass and obesity hormones.

Effect of metformin on germ cell-specific apoptosis, oxidative stress and epididymal sperm quality after testicular torsion/detorsion in rats.

The study was designed to evaluate the effects of metformin on apoptosis and epididymal sperm quality in a rat testicular ischaemia/reperfusion (I/R) injury model. A total of 72 male rats were divided into four groups (n = 18 for each group): group 1 (sham-operated group), group 2 (metformin group), group 3 (torsion/detorsion [T/D] + saline) and group 4 (T/D + 300 mg kg-1 metformin). Testicular torsion was achieved by rotating the right testis 720° in a clockwise direction for 1 hr. Tissue malondialdehyde (MDA) level and caspase-3 activity increased and the activities of catalase, superoxide dismutase and glutathione peroxidase decreased in comparison with sham-operated group 4 hr after detorsion (p < .001). In six rats of each group 24 hr after detorsion, histopathological changes and germ cell apoptosis were significantly deteriorated by measuring mean of seminiferous tubule diameters (MSTD) and TUNEL test. Moreover, 30 days after T/D, sperm concentration and motility were examined in six animals per group. Metformin pre-treatment reduced MDA and caspase-3 levels and normalised antioxidant enzyme activities 4 hr after detorsion, and germ cell apoptosis was significantly decreased, and the MSTD, as well as sperm functions, was significantly improved. Reduction in oxidative stress and apoptosis may have a major role in cytoprotective effects of metformin.

Effect of conjugated linoleic acid on blood inflammatory markers: a systematic review and meta-analysis on randomized controlled trials.

BACKGROUND/OBJECTIVES: Conjugated linoleic acid (CLA) is a polyunsaturated fatty acid with attractive biological activities. Numerous studies have been conducted on the inflammation-lowering effects of CLA in in vitro and animal models. However, the effects of CLA treatment on the inflammatory markers in humans are controversial. Therefore, the objective of this study was to perform a systematic review and meta-analysis on controlled clinical trials (RCT) assessing the effects of CLA supplementation on the circulating inflammatory markers, including C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). SUBJECTS/METHODS: The literature search of RCTs was performed using Pubmed/Medline, Scopus, ScienceDirect, Web of science, Cochrane, and Google Scholar databases from inception to March 2017. Weighted mean differences were estimated and the pooled effect size was calculated by a random effects model. RESULTS: Of the 427 identified studies, eleven RCTs, including 420 subjects were included in the statistical analysis. Findings suggested that CLA supplementation increased blood levels of CRP by 0.89 mg/l (95% CI: 0.11, 1.68; P = 0.025) and TNF-α levels by 0.39 pg/ml (95% CI: 0.23, 0.55; P < 0.0001). However, blood IL-6 levels were marginally decreased by 0.32 pg/ml (95% CI: -0.71, 0.07; P = 0.11) following CLA supplementation. There was a significant heterogeneity for the impact of CLA on CRP and IL-6, but not TNF-α. CONCLUSIONS: This meta-analysis showed that CLA supplementation may increase inflammatory markers (CRP and TNF-α). There are concerns about using CLA supplementation as an anti-obesity agent among the obese population for at least a short duration.

Effect of Green Tea on Plasma Adiponectin Levels: A Systematic Review and Meta-analysis of Randomized Controlled Clinical Trials.

OBJECTIVE: Our objective was to perform a systematic review and meta-analysis on randomized controlled trials (RCTs) assessing the effect of green tea on serum adiponectin concentration. METHOD: We searched PubMed, ISI Web of Science, Scopus, and the Google Scholar databases up to November 2016. RCTs conducted among human adults studied the effects of green tea and green tea extract on serum adiponectin concentrations as an outcome variable was included. The weighted mean differences and standard deviations (SD) of change in serum adiponectin levels were calculated. The random effects model was used for deriving a summary of mean estimates with their corresponding SDs. The protocol was registered with PROSPERO (No. CRD42017057716). RESULT: Fourteen RCTs were eligible to be included in the systematic review and the meta-analysis. Our analysis showed that green tea did not significantly affect adiponectin concentrations in comparison with placebo (weighted mean difference = -0.02 µg/ml, 95% confidence interval [CI], -0.41, 0.38; p = 0.936). There was a substantial heterogeneity between studies (I2 = 91.7%; p < 0.0001). Subgroup analyses based on sex, type of intervention, continent, and body mass index (BMI) could not explain the sources of heterogeneity. Metaregression analyses revealed that the dose and duration of green tea ingestion did not have any effect on adiponectin concentrations. CONCLUSION: Green tea could not change the circulatory adiponectin levels. The dose and duration of green tea could not change the result. RCTs with longer follow-up periods and higher doses are needed to replicate our results.

Alterations in Lipid Profile, Zinc and Copper Levels and Superoxide Dismutase Activities in Normal Pregnancy and Preeclampsia.

BACKGROUND: Increased oxidative stress (OS) and lipid peroxidation may be involved in the pathogenesis of preeclampsia (PE). We conducted a case-control study to evaluate the levels of plasma lipids and trace elements as well as activity of superoxide dismutase (SOD) in PE. MATERIALS AND METHODS: The study consisted of 100 patients who had been diagnosed with PE and 100 normotensive pregnant women who underwent medical checkups that served as the control group. Lipid profile, zinc (Zn) and copper (Cu) levels and SOD activities were measured in the plasma of all subjects. RESULTS: Our results showed that the plasma levels of triglycerides and SOD activity were significantly elevated and the levels of Zn and Cu were significantly reduced in patients with PE compared with healthy controls. Increased levels of SOD may indicate antioxidant protective mechanisms against OS in PE-complicated pregnancies. This finding may suggest an involvement of OS in the pathophysiology of PE. CONCLUSION: This study demonstrated a significant negative correlation between SOD activity and levels of trace elements. Furthermore, we suggest that higher triglyceride levels and SOD activity combined with lower Zn and Cu levels may be associated with an increased risk of PE.

Nortriptyline protects testes against germ cell apoptosis and oxidative stress induced by testicular ischaemia/reperfusion.

We designed this experiment to evaluate the effects of nortriptyline on testicular injury after torsion/detorsion (T/D). Ninety-six adult Wistar rats were divided into six groups 16 each in control group (Group 1), sham operated (Group 2), T/D + saline (Group 3), and in groups 4-6; were administered 2, 10 and 20 mg kg-1 , i.p. of nortriptyline 30 and 90 min after torsion respectively. Testicular torsion was created by twisting the right testis 720° in clockwise direction for 1 h. In six rats of each group, tissue MDA level and caspase-3 activity increased and the activities of catalase, superoxide dismutase and glutathione peroxidase decreased in compared with control group 4 h after detorsion (P < 0.001). In six rats of each group 24 h after detorsion, histopathological changes and germ cell apoptosis were significantly deteriorated by measuring mean of seminiferous tubules diameters (MSTD) and TUNEL test. Moreover, 30 days after T/D, sperm concentration and motility were examined in rest of rats. Pre- and post-reperfusion nortriptyline could reduce MDA and caspase-3 levels and normalise antioxidant enzymes activities, dose dependently. Germ cell apoptosis was significantly decreased, and the MSTD, as well as sperm functions, were significantly improved. Inhibition of mitochondrial permeability transition pore is probably involved in protective effects of nortriptyline against testicular T/D cell damages.

1 H NMR-based metabolomics exploring urinary biomarkers correlated with proteinuria in focal segmental glomerulosclerosis: a pilot study.

Focal segmental glomerulosclerosis (FSGS) is a common glomerulonephritis, and its rates of occurrence are increasing worldwide. Proteinuria is a clinical defining feature of FSGS which correlates with the severity of podocyte injury in patients with nephrotic-range protein excretion. Metabolite biomarkers corresponding with the level of proteinuria could be considered as non-invasive complementary prognostic factors to proteinuria. The urine samples of 15 patients (n = 6 women and n = 9 men) with biopsy-proven FSGS were collected and subjected to nuclear magnetic resonance (NMR) analysis for metabolite profiling. Multivariate statistical analyses, including principal component analysis and orthogonal projection to latent structure discriminant analysis, were applied to construct a predictive model based on patients with proteinuria >3000 mg/day and <3000 mg/day. In addition, random forest was performed to predict differential metabolites, and pathway analysis was performed to find the defective pathways responsible for proteinuria. Ten metabolites, significant in both statistical methods (orthogonal projection to latent structure discriminant analysis and random forest), were considered as prognostic biomarkers for FSGS: citrulline, dimethylamine, proline, acetoacetate, alpha-ketoisovaleric acid, valine, isobutyrate, D-Palmitylcarnitine, histidine, and N-methylnicotinamide. Pathway analysis revealed impairment of the branched-chain amino acid degradation pathways in patients with massive proteinuria. This study shows that metabolomics can reveal the molecular changes corresponding with disease progression in patients with FSGS and provide a new insight for pathogenic pathways. Copyright © 2016 John Wiley & Sons, Ltd.

Pro-oxidant-antioxidant balance in Iranian veterans with sulfur mustard toxicity and different levels of pulmonary disorders.

OBJECTIVE: Sulfur mustard (SM) is a strong alkylating agent that primarily targets the skin, eye and lung. The current study evaluated the pro-oxidant-antioxidant balance (PAB) assay in human serum of SM-exposed patients. DESIGN AND METHODS: sera of 35 SM-exposed patients and 19 healthy volunteers were recruited. Both groups had nonsmoker and nonalcoholic people with no diseases such as diabetes, heart disease and other pulmonary diseases (COPD because of smoking, asthma and so on). All patients had documented exposure to SM. The PAB was measured. RESULTS: SM-exposed patients with normal values for pulmonary function test and severe obstructive pulmonary disease demonstrated a significant increase in PAB value in compared with healthy volunteers (the PAB values in healthy volunteers, normal and severe patients were 48.74 ± 21.07 HK, 101.45 ± 32.68 HK and 120.23 ± 31.55 HK, respectively). However, the level of oxidation is not related to the severity of disease defined by spirometry findings. A significant negative correlation was established between the PAB value and FEV1. CONCLUSIONS: The increased PAB value in chemical casualties showed that these patients are exposed to oxidative stress.