Impact of Radiation Therapy on Serum Humanin and MOTS-c Levels in Patients with Lung or Breast Cancer.

BACKGROUND: Lung and breast cancer are the most frequent causes of death from cancer globally. The objectives of this research were to evaluate the serum mitochondrial open reading frame of the 12S rRNA-c (MOTS-c) and humanin levels in lung or breast cancer patients, and investigate the impacts of radiation therapy on the circulating levels of these peptides. METHODS: 35 lung cancer patients, 34 breast cancer patients, and healthy volunteers as a control group were recruited in this prospective observatory research. Lung cancer patients with stage IIIA/IIIB were treated with paclitaxel-based chemotherapy plus radiotherapy (2 Gy per day, 30 times, 60 Gy total dose). Breast cancer stage IIA/IIB patients were treated with postoperative locoregional radiation therapy (2 Gy per day, 25 times, 50 Gy total dose). The ELISA method was used to detect serum humanin and MOTS-c levels during, before, and after radiotherapy. RESULTS: We observed marked elevations in circulating MOTS-c, but not humanin levels in patients with lung cancer (P < 0.001). Radiation therapy led to a marked augmentation in MOTS-c levels in these patients (P < 0.001). On the other hand, there was a marked decline in humanin, but not MOTS-c, levels in breast cancer patients (P < 0.001). CONCLUSION: Our research has shown, for the first time, that increased MOTS-c and decreased humanin levels play a role in lung cancer and breast cancer, respectively. Additionally, radiotherapy modifies MOTS-c levels in patients with lung, but not breast cancer.

Expression Analysis of the Small GTP-Binding Protein Rac in Pterygium

Objectives: To determine the roles of small GTP-binding proteins Rac1, Rac2, and Rac3 expression in pterygial tissue and to compare these expressions with normal conjunctival tissue. Materials and Methods: Seventy-eight patients with primary pterygium were enrolled. Healthy conjunctival graft specimens obtained during pterygium surgery were used as control tissue. The real-time polymerase chain reaction method on the BioMark HD dynamic array system was utilized in genomic mRNA for the gene expression analysis. Protein expressions were analyzed using western blot and immunohistochemical methods. Results: RAC1, RAC2, and RAC3 gene expressions in pterygial tissues were not markedly elevated when compared to the control specimens (p>0.05). As a very low level of RAC1 gene expression was observed, further protein expression analysis was performed for the Rac2 and Rac3 proteins. Western blot and immunohistochemical analysis of Rac2 and Rac3 protein expression revealed no significant differences between pterygial and healthy tissues (p>0.05). Conclusion: This is the first study to identify the contribution of Rac proteins in pterygium. Our results indicate that the small GTP-binding protein Rac may not be involved in pterygium pathogenesis.

Male- and female-specific microRNA expression patterns in a mouse model of methanol poisoning.

The aims of this study were to determine the miRNAs involved in the methanol poisoning, and identify the male- and female-specific miRNA expression patterns in mice. Methanol was applied orally at the doses of 4 g/kg and 8 g/kg to induce mild and severe methanol poisoning in Balb/c mice. miRNA expression levels were detected at 3 different time periods (30, 60, and 180 min) following methanol exposure. miRNA expression profiles were determined using the high-throughput Fluidigm BioMark real-time PCR. We observed that serum miR-206 expression in male mice and miR-6357 expression in female mice could be an indicator of methanol poisoning. miR-9-3p downregulation and miR-1187 upregulation could be important for liver tissue. miR-3106-5p and miR-133a-5p upregulations and miR-122-3p downregulation could be poison biomarkers for ocular tissue in male mice. However, miR-194-5p downregulation could be a biomarker for ocular tissue in female mice. miR-122-5p and miR-124-3p downregulations and miR-499a-5p upregulation appeared to be important for kidney tissue in male mice. miR-543 and miR-6342 upregulations could be potential candidate biomarkers for kidney tissue in female mice. Our study is the first to report that differential miRNA expressions are involved in blood and tissues in male and female mice after methanol treatment.

Evaluation of Serum Humanin and MOTS-c Peptide Levels in Patients with COVID-19 and Healthy Subjects.

BACKGROUND: Coronavirus Disease 2019 (COVID-19) is a life-threatening and persistent pandemic with high rates of mortality and morbidity. Although a dysfunction in the mitochondria occurs in COVID-19 pathogenesis, the contribution of mitochondrial-derived peptides to its pathophysiology has not yet been completely elucidated. The goals of this research were to assess the circulating humanin and mitochondrial open reading frame of the 12S rRNA-c (MOTS-c) levels in COVID-19 patients and explore the effects of antiviral drug therapy on these peptide levels. METHODS: Thirty adult COVID-19 patients and 32 gender-matched healthy volunteers were enrolled in this study. Circulating humanin and MOTS-c levels were detected using the ELISA method during pretreatment (before drug therapy) and post-treatment (on the 7th day of drug therapy). RESULTS: We found that there was significant attenuation of the serum humanin levels in COVID-19 patients (P < 0.001). However, we detected a significant augmentation in serum MOTS-c levels when compared to controls (P < 0.01 for pre-treatment and P < 0.001 for post-treatment). Interestingly, antiviral drug therapy did not modify the serum MOTS-c and humanin levels. CONCLUSION: Our findings suggest that MOTS-c and humanin were involved in the COVID-19 pathogenesis. Our data may also imply that elevated MOTS-c could act as a compensatory mechanism to eliminate the effects of decreased humanin levels.

Protective effects of verbenalin and (+)-eudesmin against 6-hydroxydopamine-induced oxidative/nitrosative stress in SH-SY5Y cells.

BACKGROUND: The purpose of this research was to study whether verbenalin, an iridoid glucoside, and (+)-eudesmin, a furofuran lignan isolated from different plant families, can attenuate cell damage and death induced by 6-hydroxydopamine (6-OHDA) in human neuroblastoma SH-SY5Y cells. METHODS: SH-SY5Y cells were incubated with 6-OHDA (35 µM) for 1 day. Verbenalin and (+)-eudesmin were administrated with various concentrations (1, 2.5, 5, 10, 20, and 50 µM) one hour before the 6-OHDA treatment. After 1 day, cell viability and neuroprotective effect were investigated with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays. Nitrosative stress was determined with measurements of nitric oxide (NO) and 3-nitrotyrosine (3-NT), a biomarker of peroxynitrite formation. RESULTS: We observed that 6-OHDA declined viability and augmented LDH leakage in SH-SY5Y cells. MTT analyses showed that pretreatment with verbenalin and (+)-eudesmin markedly prevented the toxicity due to 6-OHDA (P < 0.05). Verbenalin and (+)-eudesmin suppressed LDH release induced by 6-OHDA (P < 0.01). Although 6-OHDA treatment produced no marked effects on NO levels, (+)-eudesmin at high concentrations (10-50 µM) markedly attenuated NO levels (P < 0.01). There was a significant increase in 3-NT levels with 6-OHDA exposure in cells. Pretreatment with verbenalin, but not (+)-eudesmin, diminished 3-NT levels at low concentrations (1-20 µM) and prevented the cytotoxic effect of 6-OHDA (P < 0.01). CONCLUSION: These results indicated that verbenalin and (+)-eudesmin exert potent cytoprotective activities against cytotoxicity triggered by 6-OHDA in neuroblastoma cells. This is the first report demonstrating that verbenalin may act as a peroxynitrite scavenger.

Evaluation of the Rho-kinase gene expression and polymorphisms in adult patients with acute appendicitis: a differential impact of gender.

OBJECTIVE: Acute appendicitis represents one of the most common causes of acute intra-abdominal emergencies worldwide. In this case-control study, we aimed to investigate associations of Rho-kinase gene expression and polymorphisms with acute appendicitis in a Turkish population. We also aimed to study the effects of gender on these parameters. METHODS: A total of 93 unrelated patients with acute appendicitis and 93 healthy controls in the Department of Emergency Medicine, Erciyes University, between June 2019 and June 2021 were included in this study. Genomic DNA was isolated from peripheral leukocytes, and the LightCycler 480 II real-time polymerase chain reaction was utilized to detect Rho-kinase1 gene rs35996865 and Rho-kinase2 gene rs2230774 (Thr431Asn) polymorphisms. Quantitative real-time polymerase chain reaction was applied to determine Rho-kinase1 and Rho-kinase2 gene expressions. RESULTS: There was a marked increase in Rho-kinase1, but not in Rho-kinase2, mRNA expression, and this increase was evident only in male patients (p=0.0008). No significant differences were found in allele and genotype frequencies for Rho-kinase1 gene rs35996865 and Rho-kinase2 gene rs2230774 polymorphisms between the patients with acute appendicitis and the control group. CONCLUSIONS: Our data imply that Rho-kinase1 (rs35996865) and Rho-kinase2 (rs2230774) gene variants are not risk factors for the development of acute appendicitis in the Turkish population. However, increased mRNA expression of the Rho-kinase1 gene in males indicated that Rho-kinase1 is involved in the pathogenesis of acute appendicitis in a gender-specific way.

Evaluation of the Rho-kinase gene expression and polymorphisms in adult patients with acute appendicitis: a differential impact of gender

SUMMARY OBJECTIVE: Acute appendicitis represents one of the most common causes of acute intra-abdominal emergencies worldwide. In this case-control study, we aimed to investigate associations of Rho-kinase gene expression and polymorphisms with acute appendicitis in a Turkish population. We also aimed to study the effects of gender on these parameters. METHODS: A total of 93 unrelated patients with acute appendicitis and 93 healthy controls in the Department of Emergency Medicine, Erciyes University, between June 2019 and June 2021 were included in this study. Genomic DNA was isolated from peripheral leukocytes, and the LightCycler 480 II real-time polymerase chain reaction was utilized to detect Rho-kinase1 gene rs35996865 and Rho-kinase2 gene rs2230774 (Thr431Asn) polymorphisms. Quantitative real-time polymerase chain reaction was applied to determine Rho-kinase1 and Rho-kinase2 gene expressions. RESULTS: There was a marked increase in Rho-kinase1, but not in Rho-kinase2, mRNA expression, and this increase was evident only in male patients (p=0.0008). No significant differences were found in allele and genotype frequencies for Rho-kinase1 gene rs35996865 and Rho-kinase2 gene rs2230774 polymorphisms between the patients with acute appendicitis and the control group. CONCLUSIONS: Our data imply that Rho-kinase1 (rs35996865) and Rho-kinase2 (rs2230774) gene variants are not risk factors for the development of acute appendicitis in the Turkish population. However, increased mRNA expression of the Rho-kinase1 gene in males indicated that Rho-kinase1 is involved in the pathogenesis of acute appendicitis in a gender-specific way.

Effects of different-intensity exercise and creatine supplementation on mitochondrial biogenesis and redox status in mice.

Objectives: Dietary supplementation combined with exercise may potentiate the beneficial effects of exercise by reducing exercise-induced oxidative stress and improving mitochondrial quality and capacity. In this study, the effects of creatine monohydrate (CrM) supplementation with low and high-intensity exercise on mitochondrial biogenesis regulators, Nrf2 anti-oxidant signaling pathway and muscle damage levels were investigated. Materials and Methods: Balb/c male mice were divided into six experimental groups: control, control+CrM, high-intensity exercise, high-intensity exercise+CrM, low-intensity exercise, and low-intensity exercise+CrM. Mice were given CrM supplementation and at the same time, low and high-intensity exercise was applied to the groups on the treadmill at 30min/5day/8week. Then, mitochondrial biogenesis marker (PGC-1α, NRF-1, TFAM), Nrf2 and HO-1 protein expressions, total oxidant-anti-oxidant status level, and histopathological changes were investigated in serum and muscle tissue. Results: Exercise intensity and CrM supplementation were found to be effective factors in mitochondrial biogenesis induction via the PGC-1α signaling pathway. Nrf2 and HO-1 protein levels increased with exercise intensity, and this result was directly related to serum oxidative stress markers. In addition, CrM supplementation was effective in reducing exercise-induced muscle damage. Conclusion: This combination induced skeletal muscle adaptations, including mitochondrial biogenesis and enhanced anti-oxidant reserves. This synergistic effect of dietary supplementation with low-intensity exercise may be valuable as a complement to treatment, especially in diseases caused by mitochondrial dysfunction.

Evaluation of the rs35996865 polymorphism of the ROCK1 gene in sepsis.

OBJECTIVE: Sepsis is a complex and serious medical condition resulting from the activation of an innate host response to infections. The etiology of sepsis is complex and can be influenced by genetic susceptibility. The purpose of the present study was to investigate a possible association of Rho-kinase 1 (ROCK1) gene polymorphism with sepsis in a Turkish population. METHODS: The study group consisted of 100 unrelated patients with sepsis and 100 healthy controls. Genomic DNA was isolated from peripheral leukocytes from EDTA-containing blood using the QIAamp DNA Blood Mini Kit. ROCK1 gene rs35996865 and rs112130712 (Lys1054Arg) polymorphisms were analyzed in genomic DNA using the LightCycler 480 II real-time polymerase chain reaction. RESULTS: There were no significant differences in allele and genotype frequencies for ROCK1 gene rs35996865 polymorphism between the patients with sepsis and control group (p>0.05). Additionally, no association was detected between the rs35996865 polymorphism and mortality in the patient group. No polymorphism was detected with ROCK1 gene rs112130712 (Lys1054Arg) in our study groups. CONCLUSIONS: Our data showed that there is no marked association between the rs35996865 polymorphism and sepsis. Therefore, these results suggest that ROCK1 gene rs35996865 polymorphism is not risk factor for the development of sepsis in the Turkish population.

Evaluation of the rs35996865 polymorphism of the ROCK1 gene in sepsis

SUMMARY OBJECTIVE: Sepsis is a complex and serious medical condition resulting from the activation of an innate host response to infections. The etiology of sepsis is complex and can be influenced by genetic susceptibility. The purpose of the present study was to investigate a possible association of Rho-kinase 1 (ROCK1) gene polymorphism with sepsis in a Turkish population. METHODS: The study group consisted of 100 unrelated patients with sepsis and 100 healthy controls. Genomic DNA was isolated from peripheral leukocytes from EDTA-containing blood using the QIAamp DNA Blood Mini Kit. ROCK1 gene rs35996865 and rs112130712 (Lys1054Arg) polymorphisms were analyzed in genomic DNA using the LightCycler 480 II real-time polymerase chain reaction. RESULTS: There were no significant differences in allele and genotype frequencies for ROCK1 gene rs35996865 polymorphism between the patients with sepsis and control group (p>0.05). Additionally, no association was detected between the rs35996865 polymorphism and mortality in the patient group. No polymorphism was detected with ROCK1 gene rs112130712 (Lys1054Arg) in our study groups. CONCLUSIONS: Our data showed that there is no marked association between the rs35996865 polymorphism and sepsis. Therefore, these results suggest that ROCK1 gene rs35996865 polymorphism is not risk factor for the development of sepsis in the Turkish population.

Investigation of Dynamic Thiol/Disulfide Homeostasis and Nitrosative Stress in Patients with Wilson Disease.

BACKGROUND: Wilson disease (WD) is an autosomal recessive inherited disorder of copper (Cu2+) metabolism, resulting in Cu2+ accumulation and liver and central nervous system toxicity. Oxidative stress may have a role in the pathogenesis of Wilson disease, but the roles of thiol/disulfide homeostasis and nitrosative stress have not been examined. The purpose of this study was to evaluate whether there is a modification in thiol/disulfide homeostasis and nitrosative stress in patients with Wilson disease. METHODS: A total of 50 patients with Wilson disease (42 under drug treatment and 8 newly diagnosed patients with no drug treatment) and 50 healthy gender- and age-matched controls were enrolled for this study. Serum native thiol and total thiol levels were measured with a spectrophotometric method. The number of disulfide bonds and the related ratios were determined from these measurements. Serum nitric oxide (NO) and 3-nitrotyrosine (3-NT) levels were analyzed using chemiluminescence and ELISA assays, respectively. RESULTS: The average native thiol levels of the patient group under drug treatment were found to be markedly higher than the levels of controls (P < .05). We detected no marked changes in total thiol and disulfide levels, and disulfide/total thiol, disulfide/native thiol, or native thiol/total thiol ratios between groups. We found significant elevations in NO levels in Wilson disease group before drug treatment, and the 3-NT levels in the Wilson disease groups prior to (P < .05) and under drug treatment (P < .01), when compared to controls. CONCLUSION: Our data are the first to show that nitrosative stress and thiol/disulfide homeostasis can contribute to the pathogenesis of Wilson disease.

Effects of antiviral drug therapy on dynamic thiol/disulphide homeostasis and nitric oxide levels in COVID-19 patients.

The novel coronavirus disease 2019 (COVID-19) has led to a serious global pandemic. Although an oxidative stress imbalance occurs in COVID-19 patients, the contributions of thiol/disulphide homeostasis and nitric oxide (NO) generation to the pathogenesis of COVID-19 have been poorly identified. Therefore, the aim of this study was to evaluate the effects of antiviral drug therapy on the serum dynamics of thiol/disulphide homeostasis and NO levels in COVID-19 patients. A total of 50 adult patients with COVID-19 and 43 sex-matched healthy control subjects were enrolled in this prospective study. Venous blood samples were collected immediately on admission to the hospital within 24 h after the diagnosis (pre-treatment) and at the 15th day of drug therapy (post-treatment). Serum native thiol and total thiol levels were measured, and the amounts of dynamic disulphide bonds and related ratios were calculated. The average pre-treatment total and native thiol levels were significantly lower than the post-treatment values (P < 0.001 for all). We observed no significant changes in disulphide levels or disulphide/total thiol, disulphide/native thiol, or native thiol/total thiol ratios between pre- and post-treatments. There was also a significant increase in serum NO levels in the pre-treatment values when compared to control (P < 0.001) and post-treatment measurements (P < 0.01). Our results strongly suggest that thiol/disulphide homeostasis and nitrosative stress can contribute to the pathogenesis of COVID-19. This study was the first to show that antiviral drug therapy can prevent the depletion in serum thiol levels and decrease serum NO levels in COVID-19 patients.

Comparison of serum dynamic thiol/disulphide homeostasis and nitric oxide levels of total intravenous vs inhaled anaesthesia in endoscopic transsphenoidal pituitary surgery.

BACKGROUND: Transsphenoidal pituitary surgery (TPS) is traditionally performed under general anaesthesia. This study aimed to compare the effects of total intravenous anaesthesia (TIVA) or sevoflurane, an inhalation anaesthetic, on thiol-disulphide homeostasis in patients undergoing endoscopic endonasal TPS. METHODS: In this study, 84 patients scheduled for TPS were randomly categorised into two groups: propofol (n = 42, the TIVA group) or sevoflurane (n = 42, the SEVO group). Blood samples were taken before induction of general anaesthesia and at the 30 minutes of postoperation. Serum native thiol and total thiol levels were detected, and the number of dynamic disulphide bonds and related ratios were calculated from these values. Serum nitric oxide (NO) levels were measured using a chemiluminescence method. RESULTS: Although native thiol levels in TIVA postoperation group were markedly increased (P < .05), total thiol levels in SEVO postoperation group were significantly decreased (P < .01). Disulphide levels were declined in both groups (P < .05 for TIVA and P = .001 for SEVO groups). Disulphide/native thiol (P < .05 for both groups) and disulphide/total thiol ratios (P < .05 for TIVA and P < .01 for SEVO groups) were depressed in postoperation groups. We found a marked elevation in native thiol/total thiol ratio in both groups (P < .05 for TIVA and P < .01 for SEVO groups). There was significant augmentation in serum NO levels in the SEVO postoperation group (P < .05). CONCLUSION: These results are the first to show that both TIVA and sevoflurane showed similar antioxidant effect with reduced disulphide levels, but sevoflurane may offer more robust oxidative stress protection and augmented NO production than TIVA during TPS. However, the clinical effect is needed to further investigate.

Predictive Value of Neutrophil-to-Lymphocyte, Aspartate-to-Alanine Aminotransferase, Lymphocyte-to-Monocyte and Platelet-to-Lymphocyte Ratios in Severity and Side of Carotid Artery Stenosis: Are Those Significant?

BACKGROUND: Atherosclerosis is a chronic disease that leads to mortality and morbidity by affecting arterial vascular structures. Carotid artery is one of these arterial structures and occlusive disease of carotid artery may cause stroke or cranial ischemic infarction. Inflammation plays a role in the atherosclerotic process. In this study, we aimed to discuss the relationship between the severity and side of carotid artery occlusion and novel inflammatory parameters include platelet-to-lymphocyte, neutrophil-to- lymphocyte, lymphocyte-to-monocyte, and aspartate-to-alanine aminotransferase ratios. METHODS: One-hundred-fifteen patients who had carotid artery stenosis between 50%-99% and 115 healthy subjects with no carotid artery stenosis or additional disease were included in the study. The relationship between the side and degree of the lesion and platelet-to-lymphocyte, neutrophil-to-lymphocyte, lymphocyte-to-monocyte, and aspartate-to-alanine aminotransferase ratios were studied in the patient group. The patients with carotid artery stenosis and the healthy subjects were compared, in the terms of same parameters. Data were evaluated statistically. RESULTS: There were no statistically significant differences between the groups, in the terms of platelet-to-lymphocyte, neutrophil-to-lymphocyte, lymphocyte-to-monocyte, and aspartate-to-alanine aminotransferase ratios and the degree of stenosis. There was no statistically significant difference between the sides of the lesions and the parameters above except lymphocyte-to-monocyte ratio. It was statistically significantly higher in left-sided lesions. Aspartate-to- alanine aminotransferase and neutrophil-to-lymphocyte ratios were markedly higher in the patient group, when compared to controls. CONCLUSION: Platelet-to-lymphocyte, neutrophil-to-lymphocyte, lymphocyte-to-monocyte, and aspartate-to- alanine aminotransferase ratios are inexpensive, easy, fast, and reproducible parameters that can be used in determining the prediction of carotid artery stenosis.

Serum vitamin D, vitamin D binding protein levels and leukocyte vitamin D receptor gene expression in patients with ischaemic stroke.

OBJECTIVE: To investigate the possible contributions of serum 25 hydroxyvitamin D and vitamin D binding protein levels along with leukocyte vitamin D receptor gene expression in patients with ischaemic stroke. METHODS: The randomised controlled single-blind study was conducted at the Mayo Hospital, Lahore, Pakistan, from September 2015 to September 2017, and comprised patients aged 40-75 years with Arbeitsgemeinschaft für Osteosynthesefragen type A2 and A3 per trochanteric fracture. The patients randomised into two equal groups. In Group A, patients were treated by closed reduction and internal fixation with dynamic hip screw, while those in Group B were treated by closed reduction and internal fixation by proximal femoral nail. Follow-up was done at 2nd, 6th and 12th weeks, and at 6th, 9th and 12th month post-operatively. Variables evaluated were frequency of union, surgical time, approximate amount of blood loss and complications. The functional assessment was done by using Harris hip score. SPSS 20 was used for data analysis. RESULTS: Of the 90 subjects, 51 (56.6%) were cases with a mean age of 65.2±14.3 years, and 39 (43.3%) were controls with a mean age of 61.1±16.7 years. There was no difference between the groups with respect to vitamin D deficiency, serum vitamin D binding protein levels and leukocyte vitamin D receptor gene expressions (p>0.05). A negative correlation was found between 25-hydroxyvitamin D levels and the severity of ischaemic stroke (p=0.0342). CONCLUSION: There was a correlation between serum 25-hydroxyvitamin D levels and severity of ischaemic stroke as assessed by the National Institutes of Health Stroke Scale.

Investigation of Dynamic Thiol/Disulfide Homeostasis in Children With Acute Immune Thrombocytopenia.

Oxidative stress may play a role in the pathogenesis of immune thrombocytopenia (ITP), but the role of dynamic thiol/disulfide homeostasis has not been studied. The objective of this study was to assess whether there is a change in thiol/disulfide homeostasis in children with acute ITP. A total of 40 children with acute ITP and 50 healthy age-matched and sex-matched controls were included in this study. Serum total thiol and native thiol levels have been measured with a novel automatic spectrophotometric method. The amount of dynamic disulfide bonds and related ratios were calculated from these values. The average total thiol and native thiol levels of the patient group were found to be significantly lower than those levels of controls (P<0.01). However, intravenous immunoglobulin (IVIG) treatment with 1 g/kg/d prevented these reductions. disulfide level was slightly, but not significantly, depressed in ITP patients, but it recovered following IVIG treatment. We detected no marked changes in disulfide/total thiol, disulfide/native thiol, and native thiol/total thiol ratios between groups. These results are the first to demonstrate that thiol/disulfide homeostasis plays a role in ITP pathogenesis, and IVIG treatment can prevent the reduced thiol levels in children.

Determination of dynamic thiol/disulphide homeostasis in children with tetralogy of Fallot and ventricular septal defect.

Oxidative stress may contribute to the pathogenesis of congenital heart defects, but the role of dynamic thiol/disulphide homeostasis has not been evaluated. The objective of this study was to assess whether there are changes in thiol/disulphide homeostasis and nitric oxide levels in children with tetralogy of Fallot (TOF) and ventricular septal defect (VSD). A total of 47 children with congenital heart defects (24 TOF and 23 VSD) and 47 healthy age- and sex-matched controls were included in this study. Serum total thiol and native thiol levels were measured using a novel automatic spectrophotometric method. The amount of dynamic disulphide bonds and related ratios were calculated from these values. Serum nitric oxide levels were detected using a chemiluminescence assay. We found that the average native thiol, total thiol, and disulphide levels were decreased in patients with VSD when compared with healthy individuals (p < 0.001, p < 0.001, and p < 0.01, respectively). While native thiol levels were decreased (p < 0.01), disulphide levels were elevated in the TOF group (p < 0.05). We observed marked augmentation of disulphide/native thiol (p < 0.001) and disulphide/total thiol ratios (p < 0.01) in the TOF group. However, there was a significant decrease in native thiol/total thiol ratio in patients with TOF. No significant changes in these ratios were noted in the VSD group. We detected significant elevations in serum nitric oxide levels in children with TOF and VSD (p < 0.001 for all). These results are the first to demonstrate that thiol/disulphide homeostasis and nitric oxide are associated with TOF and VSD in children.

Dynamic thiol/disulfide homeostasis in children with community-acquired pneumonia.

BACKGROUND: Alteration in thiol level under oxidative stress may contribute to community-acquired pneumonia (CAP). The goal of this study was to determine whether there are changes in thiol/disulfide homeostasis and nitric oxide (NO) in children with CAP. METHODS: In total, 130 participants were involved in the study. Of these, 65 had been diagnosed with CAP on admission, and the remaining 65 were healthy individuals. Serum total thiol and native thiol were measured in each participant using a novel automated spectrophotometric method. The amount of dynamic disulfide bonds and related ratios were calculated from these values. Serum NO was measured on chemiluminescence assay. RESULTS: Average native thiol, total thiol, and disulfide in the CAP group were significantly lower than in the healthy individuals (P < 0.0001, P < 0.0001, P = 0.0126, respectively). In addition, disulfide/native thiol (P = 0.0002), and disulfide/total thiol ratios (P = 0.0004) were significantly higher, whereas the native thiol/total thiol ratio (P = 0.0004) was lower in the CAP group. High serum NO was noted in the CAP group (P = 0.0003), but there was no marked correlation between thiol/disulfide and NO. CONCLUSION: The changes in endogenous thiol levels under oxidative stress may be associated with the pathogenesis of CAP in pediatric patients.

Increased Expressions of ICAM-2 and ICAM-3 in Pterygium.

Purpose: Pterygium, one of the most common ocular surface diseases, is characterized by inflammatory infiltrates, proliferation, angiogenesis, fibrosis, and extracellular matrix breakdown. The objective of this study was to elucidate the levels of the intercellular adhesion molecule (ICAM)-2, and ICAM-3 gene and protein expressions in pterygium. Methods: A total of 59 patients with pterygium were included in this study. mRNA from pterygial and conjunctival autograft tissues were extracted, and real-time polymerase chain reaction on the BioMark HD dynamic array system was performed for the ICAM-2 and ICAM-3 gene expressions. ICAM-2 and ICAM-3 protein expressions using western blot and immunohistochemistry methods were also investigated in pterygial and conjunctival autograft tissues. Results: ICAM-2 and ICAM-3 gene expressions were markedly augmented in pterygial tissues (P = 0.0018 and P = 0.0023, respectively). Significant increases in protein expressions in pterygial tissues were also detected for ICAM-2 and ICAM-3 (P = 0.0116 and P = 0.0252, respectively). In the immunohistochemical studies, there was a marked increase in ICAM-3 (P = 0.0152), but not in ICAM-2 (P = 0.1041), protein expressions in pterygial tissues. Significant positive correlations between pterygia grading with ICAM-2 protein expression (P = 0.0398) and ICAM-3 immunohistochemical scores (P = 0.0138) were observed. Conclusion: These results demonstrate, for the first time, the expressions of ICAM-2 and ICAM-3 in the pterygium. These findings may help to understand the signal transduction mechanisms in the pterygium formation and provide a new therapy strategy for pterygium treatment.

Contribution of the Rho-kinase to Systemic Sclerosis and Behçet's Disease.

BACKGROUND: The small GTPase Rho family and its effectors, Rho-kinases (ROCK) play essential roles in the actin cytoskeleton organization and coordinate a broad range of cellular functions, such as inflammatory responses, cell contractility, migration, adhesion, proliferation, and apoptosis. METHODS: The goal of this work is to review existing literature about systemic sclerosis and Behçet's disease in relation to ROCK. RESULTS: There are some evidence that ROCK expression is elevated in patients with systemic sclerosis and Behçet's disease. Rho/ROCK gene polymorphisms have been shown to be associated with these disorders. Endothelial function is also impaired in these autoimmune diseases. Rho/Rho-kinase pathway might have a crucial role in endothelial, vascular, and fibrotic pathologies. CONCLUSION: Dysregulation in the Rho/ROCK pathway may represent a common pathogenic mechanism in multiple autoimmune disorders. Current evidence indicate that Rho/ROCK genes might be risk factors, and can contribute to susceptibility and development of systemic sclerosis and Behçet's disease. These studies may also provide important insights into the future development or use of potential novel therapeutic approaches, such as selective Rho-kinase inhibitors, for the treatment of patients with systemic sclerosis and Behçet's disease.