دکتر سید اسحاق هاشمی

Multiple sclerosis (MS) is a demyelination disorder of the central nervous system (CNS), which is believed to be associated with oxidative stress. Therefore, researchers try to find reliable biomarkers to monitor the disease and predict its prognosis. Cholesterol and lipids in the myelin sheath are vital for nerve cells. Serum low-density lipoprotein (LDL) is susceptible to lipid peroxidation induced by oxidative stress. This study aimed to evaluate oxidative stress markers in the serum of patients with relapsing-remitting MS (RRMS) and examine their correlation with lipid markers.

A total of 18 MS patients (14 women and 4 men) and 18 healthy subjects (matched by age and sex) were enrolled in this cross-sectional study. The serum samples were collected in both relapsing and remitting phases. The prooxidant-antioxidant balance (PAB), malondialdehyde (MDA), and oxidized LDL (oxLDL) were measured as markers of oxidative stress.

The mean age of participants was 29.21 (22-42) years. In the comparison between the patient and control groups, the most differences were increased levels of PAB in the patient group (P < 0.05), no difference between relapsing and remitting phases (P = 0.995), increased MDA levels in the relapsing phase (P = 0.013)––but no change in the remitting phase (P = 0.068), no difference in LDL and oxLDL levels in the patient group (P > 0.05), and MDA, LDL, and oxLDL levels did not have any significant correlation with PAB (P > 0.05).

High levels of oxidative stress markers were present in both phases of the disease. Lipid peroxidation markers (such as MDA) increased in the acute phase, but oxLDL did not change. Also, there was no significant correlation between oxidative stress and cholesterol markers.

Colorectal cancer (CRC) is one of the most common human cancers. Currently, carcinoembryonic antigen (CEA) is used as the main standard biomarker of CRC, though this biomarker is not specifically made for CRC and, in a minority of cases, shows inadequate sensitivity. Therefore, searching for novel accessory biomarkers may fill these gaps in clinical management. miRNAs physiologically regulate various metabolic processes and are misregulated in various cancers. Therefore, the present investigation was conducted to evaluate miR-1 levels in CRC samples.

The CRC and adjacent tissue samples were obtained from 24 patients. In addition, sera were collected from the patient group and 24 healthy controls. Total RNA was extracted from tissue samples, and cDNA was synthesized. Real-time PCR determined the expression of miR-1. Serum levels of CEA were also measured using a Monobind ELISA assay kit.

The level of miR-1 in CRC tumors was significantly down-regulated. Moreover, patients with metastasis showed lower expression of miR-1 compared to cases without metastasis; however, this difference was not statistically significant. The ROC curve for miR-1 showed an AUC of 0.69. In addition, ROC analysis revealed a sensitivity of 70.27% and a specificity of 62.96% for miR-1.

There is still a need for new upcoming markers in addition to the main CRC biomarker, CEA. The levels of miR-1 in colorectal cancer tissue samples may provide additional information for the management and follow-up of CRC patients; though, the clinical application needs further studies.

Bladder cancer is one of the most common genitourinary cancers with significant mortality. Finding reliable tumor markers and potential drug targets can improve early diagnosis, prognosis, and more effective therapeutic protocols. Previous studies have reported the involvement of the substance P (SP)/neurokinin-1 receptor (NK-1R) system in cancers. The potential prognostic role and the interaction of SP and NK-1R in bladder tumor are yet to be elucidated.

Serum samples from 22 primarily diagnosed patients with bladder cancer as well as 22 healthy controls were examined for SP level using ELISA method. Tissue distribution of NK-1R in tumor samples and their adjacent normal tissues was evaluated through immunohistochemistry.esults: Serum SP levels in patients with bladder cancer were higher than the healthy group (p< 0.001) and had a significant correlation with NK-1R staining intensity (p< 0.001), percentage of stained cells (p< 0.001), and NK-1R tissue distribution. Also, the immunoreactivity of NK-1R in cancer samples increased significantly without correlation with tumor characteristics. However, no significant association was found between SP and NK-1R levels with clinical characteristics including tumor size (p= 0.33), tumor stage (p= 0.29), grade (p= 0.93), NK-1R staining intensity (p= 0.53), and percentage of stained cells (p= 0.32).

According to our findings, despite the lack of association between SP and NK-1R with clinical characteristics of bladder cancer, their serum levels were higher in patients with bladder cancer. Further studies are needed to confirm the potential prognostic role of SP and NK-1R in bladder cancer.

Metabolic syndrome is a multifactorial disorder characterized by hyperglycemia, hyperlipidemia, obesity, and hypertension risk factors. Moreover, metabolic syndrome is the most ordinary risk factor for cardiovascular disease (CVD). Numerous chemical drugs are being synthesized to heal metabolic risk factors. Still, due to their abundant side effects, herbal medicines have a vital role in the treatment of these abnormalities. Ginger (Zingiber officinale Roscoe, Zingiberaceae) plant has been traditionally used in medicine to treat disorders, including CVD. The unique ginger properties are attributed to the presence of [6]-gingerol, [8]-gingerol, [10]-gingerol, and [6]-shogaol, which through different mechanisms can be beneficial in metabolic syndrome. Ginger has a beneficial role in metabolic syndrome treatment due to its hypotensive, anti‐obesity, hypoglycemic, and hypolipidemic effects. It can significantly reduce atherosclerotic lesion areas, VLDL and LDL cholesterol levels, and elevate adenosine deaminase activity in platelet and lymphocytes. Also, it promotes ATP/ADP hydrolysis. In the current article review, the critical properties of ginger and its constituents’ effects on the metabolic syndrome with a special focus on different molecular and cellular mechanisms have been discussed. This article also suggests that ginger may be introduced as a therapeutic or preventive agent against metabolic syndrome after randomized clinical trials.

Clinical education is the heart of medical education. It is one of the most important manifestations of teaching and learning in professions relating to medical sciences, leading to learners' clinical competency. This study was done to investigate general physician graduates' knowledge, performance, and clinical competency before entering the field of clinical activities. In this descriptive cross-sectional study, the scores of different stations of the Objective Structured Clinical Examination (OSCE), held at the end of the general medicine course in Iran, were collected at Mashhad University of Medical Sciences. Totally, 266 students who participated in six periodicities of clinical competency examinations were included in the study by the census method. The clinical competency of general physician graduates assessed in the scopes were determined by the General Medical Education Council, including problem-solving, communication skills, practical action, taking the history, and performing physical examinations by the OSCE. The data were analyzed by SPSS software using descriptive and inferential statistics. The effect of different scopes of the OSCE (F(3,5652) = 7.022 and P = 0.001) and participants' performance based on their critical and non-critical indicators (T = 1.976 and P = 0.04) are significant with 95% confidence interval. This suggests that participants' performance varies in different scopes of the clinical examination, including problem-solving, communication skills, practical action, taking the history, and performing physical examinations. The differences in the clinical competencies of general physician graduates in mentioned scopes were significant. This emphasizes the need to examine their essential skills to achieve the minimum competencies expected of a future physician before entering the field of clinical activity.

Metabolic syndrome (MetS) is characterised by a clustering of metabolic cardiovascular disease (CVD) risk factors that include: central obesity, impaired glucose metabolism, dyslipidaemia (hypertriglyceridemia, increased low-density lipoprotein [LDL], decreased high-density lipoprotein [HDL]) and hypertension. Paraoxynase-1 (PON1) is a plasma HDL associated protein that inhibits the oxidation of other lipoproteins. There is some evidence of reduced enzyme activity in subjects with metabolic syndrome. Curcumin is a natural polyphenol, it has been reported that curcumin has beneficial effects on several metabolic syndrome associated parameters. The aim of this study was to evaluate the effect of phospholipid complex of curcumin as an antioxidant on the activity of this enzyme in subjects with metabolic syndrome. A double-blind randomised control study was undertaken in 80 patients with metabolic syndrome. Subjects in the intervention (n = 40) were given capsules of phospholipidated curcumin (1 g/day) for a period of 6 weeks. The control subjects (n = 40) received a placebo. Fasting blood samples of each person were obtained during the start and the end of the study. Paraoxonase activity was measured using a PON1 fluorescence Paraoxonase Assay Kit and Arylesterase activity was measured by photometeric method using a UV-Visible spectrophotometer. Serum paraoxonase enzyme activity did not change significantly between the curcumin treated group and the control group before the intervention (0.54 ± 0.18 U/µl versus 0.49 ± 0.14 U/µl; P > 0.05), nor did serum arylesteras activity change significantly between two study groups (152.67 [46.60 to 916.05] U/µl versus 129.77 [55.34 to 344.78] U/µl; P > 0.05). In addition, there was no significant difference in changes at baseline and after the intervention in serum PON1 activity between the curcumin treated group and the control group (-0.03±0.19 U/µl versus -0.04±0.18 U/µl; P > 0.05), nor was there a significant change in arylesteras activity (-12.36 [-88.83 to 110.24] U/µl versus -4.58 [-61.06 to 47.07] U/µl; P > 0.05). Phospholipid fortified curcumin has no significant effect on serum PON1 activity.

Papillary thyroid carcinoma (PTC) is the most prevalent malignancy of the endocrine system. This study was aimed at evaluating the serum substance P (SP) levels, the tissue distribution of Neurokinin-1 receptors (NK1-R), and their possible diagnostic value in PTC.

The present case-control study included 31 healthy volunteers and 31 cases (age range: 25-64, 40.26 ±12.77), who were primarily diagnosed with PTC and were candidates for total thyroidectomy. Pre-operative serum level of SP was measured using a commercial ELISA kit. The tissue distribution of NK1-R was assessed immunohistochemically.

The serum level of SP in the patient group was higher than the healthy volunteers (P = 0.005). Besides, the expression of NK1-R was higher in tumoral tissues compared with their normal surroundings (P = 0.005). However, we observed no significant correlation between either SP level or NK1-R expression and the disease stage or lymph node involvement.

SP level and NK1-R expression were upregulated in PTC patients, showing the involvement of SP/NK1R complex in PTC pathophysiology. Nonetheless, proposing SP/NK1R as a diagnostic factor requires further studies because we found no correlation between SP/NK1R and clinical stage or lymph node involvement.

The aim of this study was to evaluate the concentration of zinc finger protein 510 (ZNF510) in the saliva of patients with oral lichen planus and healthy individuals in 2019. This cross-sectional analytical study was performed on 24 patients with oral lichen planus and 25 healthy individuals referred to the School of Dentistry, Mashhad University of Medical Sciences, Mashhad, Iran, between June and October 2019. In the case group, the severity of lesions was determined according to the Thongprasom index. Unstimulated saliva was collected from the subjects and the samples were examined for the presence of the ZNF510 protein using ELISA method. The data were statistically analyzed through SPSS 23. For data analysis, Kolmogorov-Smirnov test, the independent t-test, the independent samples Kruskal-Wallis test, and one-way analysis of variance were used. This study included 32 females (65.3%), and 17 males (34.7%). The subjects’ age range was between 23-70 years and the mean age of them was 46.26 ± 10.90 years. The mean ZNF510 (ppm) in the case group was 86.12 ± 34.88, while in the control group, it was 46.43 ± 23.32. The two groups were significantly different in terms of the mean ZNF510 (P <0.001). In patients with non-keratotic lichen planus, the mean ZNF510 was significantly higher than that in those with keratotic lesions (P = 0.028). Moreover, in patients with oral lichen planus, the severity of lesions according to the Thongprasom index was significantly and directly related to the ZNF510 concentration (P = 0.002). The concentration of ZNF510 protein in the saliva can be a good indicator for assessing the severity of oral lichen planus lesions and its diagnosis. However, its clinical application is possible only if extensive prospective studies are performed.

Glioblastoma multiforme (GBM), a highly aggressive Grade IV brain tumor, is a significant public health issue due to its poor prognosis and incurability. Neuropeptide substance P (SP) plays a critical role in GBM tumor growth and development via activation of neurokinin‐1receptor (NK1R). Moreover, SP is a pro-oxidant factor contributing to oxidative stress in various cell types. However, the link between SP and oxidative stress in cancer cells is not fully investigated. Here, we aimed to identify the effects of SP and NK1R antagonist, aprepitant, on the redox status of GBM cells. Resazurin assay was employed to determine the effect of aprepitant on viability of U87 glioblastoma cells. 2’,7’-dichlorodihydrofluorescein diacetate (H2DCFDA) assay was employed to measure the levels of intracellular reactive oxygen species (ROS). A quantitative real-time polymerase chain reaction was applied to measure the expression of proteins of the thioredoxin system. Commercial kits (ZellBio GmbH) were also used to measure the enzymatic activity of these proteins. We found that SP increased ROS level in U87 GBM cells, and aprepitant significantly reduced this effect. Furthermore, we found that SP could also affect the thioredoxin system, a central antioxidant enzyme defense system. SP reduced both expression and enzymatic activity of the thioredoxin system’s proteins, Trx and thioredoxin reductase (TrxR) and these effects were significantly reduced by aprepitant. Our results indicated that SP activation of NK1R represented a link between oxidative stress and GBM and highlighted the need for further validations in future studies.

Integration is accepted as an important strategy in medical education and its final results depend on organizing different topics. In this method, the subjects (based on content) which are often included separately in a curriculum, are integrated in order to link and combine the content of the curriculum to create a cohesive learning experience. Development of this method is among the objectives of the medical education reform.

The present applied cross-sectional study was performed on a statistical population (n=602) consisting of general medicine students of Mashhad University of Medical Sciences at the level of basic sciences. The participants were selected using the census sampling method and included 150 and 130 students who were admitted in February 2017 (the reformed curriculum) and in February 2016 (the conventional curriculum), respectively. The curriculums were compared in terms of learning outcomes and the number of vulnerable students. Moreover, the research hypotheses were tested using the independent t-test and chi-square test in SPSS software (version 22).

Based on the findings, with 95% confidence, the learning outcomes of the students who followed the reformed curriculum were better than those of the students who followed the conventional curriculum. According to the analysis of the collected data, the mean learning outcomes for the conventional and the reformed curriculum groups were 14.30±3.28 and 16.76±2.80 for the subject of anatomy, 14.10±2.62 and 15.13±2.93 for the subject of physiology, and 14.35±3.13 and 15.44±2.85 for the subject of biochemistry. However, no significant difference was observed in the number of vulnerable students in two groups.

Based on the findings, basic sciences curriculum reform in medical education can improve the academic achievement of the general medicine students.

Tachykinins (TKs) are a family of neuropeptides widely distributed in the human body, especially in the nervous system. TKs have exhibited both neuroprotective and neurodegenerative properties in the central nervous system (CNS) and spinal cord. Also, several studies have shown that substance P (SP), as a pioneering neuropeptide of the TK family, is engaged in the pathogenesis of neurodegenerative disorders (NDs), such as Alzheimer disease, Multiple Sclerosis, Parkinson’s disease, Huntington’s disease, and Amyotrophic lateral sclerosis. However, a huge body of information available about the level of SP in NDs demonstrates that SP and its receptors might be prognostic or diagnostic factors for NDs. The present review article summarizes the roles of TKs in common neurodegenerative disorders.

 Tachykinins (TKs), an evolutionarily conserved family of peptide hormones, are widely distributed within the peripheral and central nervous systems. TKs exert their biological actions in many processes via three subtypes of transmembrane G-protein coupled receptors, which are NK1R, NK2R, and NK3R. Although the mechanisms that connect TKs peptide activity to physiological processes are currently precise, it has been shown that TKs over-activation is associated with the pathogenesis of many diseases, including pain, emesis, depression, stress, and inflammatory processes, as well as human tumors. Gastrointestinal (GI) cancers refer to malignant conditions of the GI tract, which are among the most prevalent diseases and are the leading cause of cancer-related death worldwide. Recent studies have shown that the binding of TKs to specific cellular receptors mediates a critical GI tumor proliferation pathway via initiation and activation of effector mechanisms, including protein synthesis and progression of the eukaryotic cell cycle.

This study reviewed the role of tachykinins in the initiation and progression of gastrointestinal cancers. In this regard we searched databases such as PubMed, Science Direct, Google Scholar, and Scopus databases by using these keywords “Tachykinins”, “Gastrointestinal cancer”, “Metastasis”, “G-protein coupled receptors”, and “pharmacological inhibitor” without any time limit. The relevance of studies was identified by reviewing the titles and the abstracts. A total of 100 English language articles including experimental, observational, molecular, and cellular studies were reviewed.

The administration of the gastrointestinal cancer cells with Tk receptor antagonists induces apoptotic cell death through the tachykinin-mediated pathway. The findings showed that the pharmacological inhibition of TKRs with its selective antagonists has a promising prospect for the GI cancers treatment approach, either as a single agent or in combination with other chemotherapeutic agents.

In this review, we presented different facts regarding the role of TKs and TKRs in the pathogenesis of GI malignancies for a better understanding and hence better management of these cancers. Therefore, understanding the underlying mechanism of the TK/TKR system can help to have a more excellent clinical vision for the treatment of GI cancers.

In recent decades, the inappropriate use of antibiotics and the existence of transferable resistant elements have caused the emergence of multidrug-resistant (MDR) gram-negative organisms. Antimicrobial resistance is becoming one of the major challenges to public health and has caused morbidity and mortality worldwide. The purpose of this study was the assessment of the prevalence and frequency of colistin resistance among gram-negative bacilli (Enterobacteriaceae, Acinetobacter spp., and Pseudomonas spp.) in Iran and around the world.

For this systematic review and meta-analysis, we searched international and national databases, including PubMed, Google Scholar, SID, and Magiran, from 1998 to 2018 for articles and abstracts describing colistin resistance among gram-negative bacilli. We have included 92 studies that met our inclusion criteria, and the outcomes were combined using a random-effects model to derive the event rate of colistin resistance among gram-negative bacilli. Data were analyzed by the Comprehensive Meta-Analysis Software (V2), and the heterogeneity of the studies was assessed using the I2 index.

Out of the 11050 papers identified, 92 studies met the strict inclusion criteria and were finally included. The overall event rate of colistin resistance among gram-negative bacilli (GNB) was about 6.6%, while the event rate of colistin resistance among Acinetobacter spp. (n = 18504) was 2.8% (summary: 95% confidence interval (CI): [0.02, 0.041], P = 0.001, I2 = 70, df (Q) = 36, Q-value = 121.924). The colistin resistance among Pseudomonas spp. (n = 15094) was 3% (95% CI: [0.022, 0.041], P = 0.001, I2 = 68.3, df (Q) = 25, Q-value = 85.648), and the colistin resistance among Enterobacteriaceae spp. (n = 44772) was 0.8% (95% CI: [0.004, 0.014], P = 0.001, I2 = 87.6, df (Q) = 15, Q-value = 71.291). Therefore, the event rate of resistance to colistin among GNB was relatively low (6.6%).

The event rate of resistance to colistin among GNB was low. Therefore, this antimicrobial agent can still be administered as a suitable option against GNB that are resistant to other antibiotics such as carbapenems.

Psoriasis is a chronic-relapsing inflammatory skin disorder, in whose pathogenesis oxidative stress is suggested to be involved. Among different enzymes that play a role in maintaining the cellular redox balance, we aimed to assess the alteration of glutathione peroxidase (GPX) activity in cutaneous lesions and its correlation with the disease severity, firstly, to support the possible candidacy of this enzyme for future topical therapeutic regimens, and secondly, to move forward in understanding the etiology of the disease and the pathogenic mechanisms involved in cutaneous lesions so as to pave the way for further investigations.

The clinical severity of disease was determined according to Psoriasis Area and Severity Index (PASI) scoring system. The level of GPX activity in the skin biopsies from 20 psoriatic patients was measured using Cayman’s glutathione peroxidase assay kit, and its association with disease severity was assessed in each patient.

Tissue GPX activity was significantly higher in patients with mild psoriasis (149.02 ± 24.213 nmol/min/ml) compared to patients with moderate psoriasis (120.58±21.038 nmol/min/ ml) (p-value < 0.05). There was a significant negative correlation between the activity of GPX and each PASI-associated criterion, including redness, scaling and thickness. Among all the criteria of PASI, scaling was independently correlated with the activity of GPX (p-value < 0.05).

The reduced activity of GPX in dermal lesions might be associated with the disease pathogenesis, having a valuable role in diagnosis and therapy.

Thioredoxin, NADPH, and thioredoxin reductase form the thioredoxinsystem which exists in all living cells. Oxidants have a major role in cancer pathogenesis;therefore, it is necessary to study the role of redox-active compounds such as thioredoxinreductase to increase our knowledge about the molecular mechanisms involved in cancerpathogenesis and ultimately design more effective treatments. The research on the roleof the thioredoxin system in pancreatic cancer is limited; hence, we intend to comparethe tissue distribution and activity of thioredoxin reductase in pancreatic cancer withhealthy tissues located at the tumor margins. A total of 29 patients with pancreatic cancer participated in this study.The tissue distribution was determined by immunohistochemistry analysis. We useda commercial ELISA kit to determine enzyme activity. There was no significant difference between the tumor tissue and itsnormal surrounding tissue in terms of thioredoxin reductase activity (P=0.56). However,there was a significant difference when we considered the different disease stages. Asignificant relationship also existed between the staining intensity of thioredoxinreductase and disease stage (P=0.022). There was no observed difference between the pancreatic cancertissue and its healthy margin in terms of thioredoxin reductase activity and tissuedistribution. This finding did not support its possible role in pancreatic cancerpathogenesis.

Finding an accurate diagnostic test can reduce the rate of unnecessary abdominal surgery in cases of suspected acute appendicitis (AA). This study aimed to evaluate the diagnostic value of serum lactoferrin (LF) and procalcitonin (PCT) in detection of patients with acute appendicitis. In this diagnostic accuracy study, screening performance characteristics of PCT and LF were calculated in patients suspected with acute appendicitis and healthy volunteers as control group. 131 cases participated (61 as case and 70 as control). The mean serum level of LF (0.9±0.14 vs 0.2±0.13 µg/ml; p 0.0001) and PCT (0.15±0.21 vs 0.11±0.02 ng/dl; p = 0.02) were significantly higher in patients suspected with AA. The AUC of PCT and LF were 0.46 (95% CI: 0.31-0.61) and 0.61 (95%CI: 0.47 - 0.76), respectively. At a 0.90 µg/ml cut-off value, LF had 77% (95 % CI: 63 - 91) sensitivity and 43% (95 % CI: 31 - 55) specificity. Also, at a 0.11 ng/dl cut-off value, PCT had 41% (95 % CI: 26 - 56) sensitivity and 69% (95 % CI: 53 - 85) specificity. Based on the main finding of present study, the overall accuracy of serum PCT and LF in detection of patients with acute appendicitis are in poor to failed range and it seems that they could not be considered as good screening tools for this purpose.

Several studies have shown the role of oxidative stress in pathophysiology of burn injuries. This study aimed to evaluate the changes of oxidant-antioxidant levels during the week following burn injuries and its correlation with grade of burn. In this prospective cross-sectional study, changes of total glutathione, reduced glutathione (GSH), oxidized GSH (GSSG), GSH/GSSG ratio, as well as Pro-oxidant-antioxidant balance (PAB) were investigated on the 1st, 2nd and 7th days of admission in patients with > 15 % burns. 40 patients with the mean age of 21.1 ± 14.5 were studied (47.5% male). More than 50% of patients were in the 18 – 55 years age range and over 70% had 20% – 60% grade of burn. Total serum glutathione level and GSH had significant decreasing trends (P < 0.001) and GSSG and GSH/GSSG ratio had increasing trends (p < 0.001). No significant correlation was observed between serum GSH level and the total body surface area (TBSA) of burn injury (r = 0.047; p = 0.779). The evaluation of PAB and its correlation with TBSA showed a significant and direct association between them on the 1st (coefficient = 0.516; p = 0.001), 2nd (coefficient = 0.62; p <0.001), and 3rd (coefficient = 0.471; p = 0.002) day of follow up. According to this study, the redox perturbation occurred in burn injury which was measured and proved by decreased GSH/GSSG ratio as well as the shift of PAB in favour of oxidants. Besides, since PAB positively correlated with the severity of dermal damage, it might suggest the application of antioxidants as a part of therapeutic protocol for which the dosage should be proportionate to the surface area of the damaged skin.

Among different mechanisms, oxidative stress has a possible role in neural injury in cerebrovascular events.
Assessment the oxidants-antioxidants imbalance in ischemic and hemorrhagic strokes.
Serum level of malondialdehyde, the main marker of lipid peroxidation, and total antioxidant capacity were measured in a group of 48 stroke patients consisting of 24 ischemic and 24 hemorrhagic cases with confirmed diagnosis by brain CT scan. Lesion volume and modified National Institutes of Health Stroke Scale (NIHSS) in ischemic stroke, as well as location and volume of hematoma in hemorrhagic stroke based on the first brain CT scan were determined as study variables.
These two major groups did not have different oxidative profile. Low levels of total antioxidant capacity and high levels of malondialdehyde were associated with higher lesion volume in hemorrhagic stroke patients.
This data suggested that oxidative stress is associated with lesion volume and therefore severity of hemorrhagic stroke.

The thioredoxin system, comprising thioredoxin (Trx), thioredoxin reductase (TrxR) and NADPH, is one of the major cellular antioxidant systems, implicated in a large and growing number of biological functions. Trx acts as an oxidoreductase via a highly conserved dithiol/disulfide motif located in the active site (-Trp-Cys-Gly-Pro-Cys-Lys-). Different factors are involved in the regulation of Trx activity, including its expression level, localization, protein-protein interactions, post-translational modifications and some chemical inhibitors.Mammalian TrxRs are selenoproteins which have a –Cys-Val-Asn-Val-Gly-Cys- N-terminal active site, as well as a C-terminal selenium-containing active site. Besides two Cys-residues in the redox-regulatory domain of cytosolic Trx (Trx1), human Trx1 has three additional Cys-residues. Post-translational modifications of human Trx1 which are involved in the regulation of its activity can happen via modification of Cys-residues including thiol oxidation, glutathionylation and S-nitrosylation or via modification of other amino acid residues such as nitration of Tyr-49.Because of the numerous functions of the thioredoxin system, its inhibition (mainly happens via the targeting TrxR) can result in major cellular consequences, which are potentially pro-oxidant in nature, leading to cell death via necrosis or apoptosis if overexpression of Trx and other antioxidative enzymes can not recuperate cell response. Considering this feature, several anticancer drugs have been used which can inhibit TrxR. Elevated levels of Trx and/or TrxR have been reported in many different human malignancies, positively correlated with aggressive tumor growth and poor prognosis. Moreover, anti-oxidative and anti-apoptotic effects of Trx are reasons to study its clinical application as a drug.