Cannabidiol as a potential novel treatment for endometriosis by its anti-inflammatory, antioxidative and antiangiogenic effects in an experimental rat model.

RESEARCH QUESTION: Can cannabidiol (CBD) be used in the treatment of endometriosis for its anti-inflammatory, antioxidative and antiangiogenic effects? DESIGN: Endometrial implants were surgically induced in 36 female Wistar albino rats. After confirmation of endometriotic foci, the rats were randomized into four groups. In the leuprolide acetate group, rats were given a single 1 mg/kg s.c. leuprolide acetate injection. The other groups were 5 mg/kg CBD (CBD5), saline solution and 20 mg/kg CBD (CBD20); daily i.p. injections were administered for 7 days. After 21 days, the rats were euthanised, and total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α) measurements in blood and peritoneal fluid samples, and immunohistochemical staining for TNF-α, IL-6 and vascular endothelial growth factor (VEGF) of endometriotic tissues were evaluated. RESULTS: Significant reductions in the endometriotic implant surface area (P = 0.0213), serum TOS (P = 0.0491), OSI (P = 0.0056), IL-6 (P = 0.0236), TNF-α (P = 0.0083) and peritoneal fluid OSI (P = 0.0401), IL-6 (P = 0.0205) and TNF-α (P = 0.0045) concentrations were observed in the CBD5 group when compared with the saline solution group. Compared with the saline solution group, increased TAS concentrations in serum (P = 0.0012) and peritoneal fluid (P = 0.0145) were found in the CBD5 group. The CBD5 and leuprolide acetate groups were similar regarding inflammatory and oxidative stress parameters of serum and peritoneal fluid samples. The CBD5 group showed significantly lower mean intensity in both surface epithelium and stromal cells for VEGF (both P = 0.002) and only in surface epithelium cells for IL-6 (P = 0.0108), when compared with the leuprolide acetate group. CONCLUSION: Due to its anti-inflammatory, antioxidative and antiangiogenic effects, CBD might be a therapeutic agent candidate for endometriosis.

Oleuropein exhibits anticarcinogen effects against gastric cancer cell lines.

BACKGROUND: Oleuropein (OLE), the main phenolic compound of the olive fruit and leaves, has many heathful effects. Gastric cancer is the most fatal malignancy in many parts of the world and it is generally related to harmful dietetic factors. The anticarcinogenic role of OLE in gastric cancer has not been studied sufficiently yet. In this study, we aimed to research the cytotoxic, genotoxic and apoptotic effects of OLE on gastric adenocancer (AGS) cells in vitro. METHODS AND RESULTS: A standard cell line derived from gastric adeno cancer (AGS) cells was employed, and its performance following a 24-hour exposure to OLE at various doses was examined. The ATP cell viability assay, 2',7'-dichlorodihydrofluorescein-diacetate assay (H2DCF-DA) and alkaline single cell gel electrophoresis assay (Comet Assay) were used to study the cytotoxicity, production of reactive oxygen species (ROS) and genotoxicity respectively. The induction of apoptosis was discovered using flow cytometry. OLE reduced AGS cells viability about 60% at maximum concentration (500 µmol/L) and also resulted in approximately 100% DNA damage and about 40% apoptosis with necrosis in AGS cells depending on the increased doses. Cell viability was also significantly decreased in relation to increased intracellular reactive oxygen species (ROS) levels (p < 0.05 - 0.001). CONCLUSIONS: Oleuropein has shown significant anticarcinogen effects against gastric adenocancer (AGS) cells in vitro. Oleuropein, a nutrient rich in olive and olive oil, seems to be both protective and therapeutic against gastric cancer and may be a new chemotherapeutic agent in the future.

Examination of antimicrobial effect of fluoxetine in experimental sepsis model: An in vivo study.

Since most infectious diseases can develop into sepsis, it is still a major medical problem. Some in-vivo studies showed promising properties of fluoxetine in the treatment of infections. This study aims the antimicrobial effect of fluoxetine on the inflammatory process used in the treatment of sepsis-modeled rats. Besides, to investigate the efficacy of fluoxetine on modifying the antibiotic effect of imipenem in the inflammatory response. An experimental sepsis model was divided into negative control, positive control, fluoxetine 5 mg/kg, imipenem 60 mg/kg, and combined (fluoxetine; imipenem). Procalcitonin (PCT), high-sensitivity C-reactive protein (hs-CRP), lactate, myeloperoxidase activity (MPO), the inflammation markers interleukin-1ß (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor-alfa (TNF-α), and monocyte chemoattractant protein-1 (MCP-1) levels were measured by enzyme-linked immunosorbent assay method. Oxidative stress markers, total oxidant status (TOS), total antioxidant status (TAS), total thiol (TT), and native thiol (NT) were measured using photometric methods. Oxidative stress index (OSI) was calculated according to TAS and TOS levels. The statistical analysis was performed by Statistical Package for Social Sciences version 22.0. After treatment with fluoxetine, imipenem, and combined groups, IL-1ß, IL-6, TNF-α, MPO activity, MCP-1, hs-CRP, PCT, lactate, and the oxidative stress markers OSI, and disulfide levels were decreased (p < 0.05). The TT, NT, and TAS levels significantly statistically increased (p < 0.05). This research demonstrates that fluoxetine has effects as anti-inflammatory and antioxidant, and the combined treatment with antibioticum imipenem indicates positive synergistic effects in the experimental sepsis model.

Changes in neuroactive steroids, neurotrophins and immunological biomarkers after monotherapy 8-week rTMS treatment and their relationship with neurocognitive functions in depression.

Repetitive transcranial magnetic stimulation (rTMS) has proven effective in the treatment of major depression. The underlying mechanisms of action are still poorly understood. We aimed to evaluate the changes in the levels of neuroactive steroids, neurotrophins and immunological biomarkers before and after rTMS treatment and assess the relationship of this change between clinical response and cognitive functions after monotherapy rTMS treatment. Twenty-three patients with major depressive disorder (MDD) and 25 matched healthy controls were included in the study. The Hamilton Depression Rating Scale (HDRS), Trail Making Test A and B forms and Digit Span Test were administered. Biomarkers (BDNF, TNF-α, IL-1ß, NAS) were run in the peripheral blood at the end of the first month that rTMS was administered daily and at the end of the 2nd month when that rTMS was administered once a week. Appropriate conditions were provided so that the relevant biomarkers were not affected by the biorhythm. After rTMS monotherapy, an increase in BDNF and allopregnanolone, a decrease in TNF-α, IL-1ß, DHEA, and DHEA-S levels was found to be statistically significant. The scores on cognitive tests increased with the treatment. Positive significant correlations was found between BDNF levels and cognitive tests at the end of the first and second months. Our findings suggest that the effects of rTMS treatment may be related to the neuroendocrine, neurotrophin, and immunological mechanisms. rTMS treatment is found to have positive effects on cognitive functions in the short term.

Clinical and biological correlates of optical coherence tomography findings in schizophrenia.

There is a growing body of evidence indicating retinal layer thinning in schizophrenia. However, neuropathological processes underlying these retinal structural changes and its clinical correlates are yet to be known. Here, we aim to investigate the clinical and biological correlates of OCT findings in schizophrenia. 50 schizophrenia patients and 40 healthy controls were recruited. Retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), and macular and choroidal thicknesses were recorded. A comprehensive battery of neuropsychological tests was applied. Fasting glucose, triglycerides and HDL-cholesterol levels, TNF-α, IL-1ß and IL-6 levels were measured. Right IPL was significantly thinner in patients than the controls after controlling for various confounders (F = 5.42, p = .02). Higher IL-6, IL-1ß, and TNF-α levels were associated with decreased left macular thickness (r = - 0.26, p = .027, r = - 0.30, p = 0.012, and r = - 0.24, p = .046, respectively) and higher IL-6 was associated with thinning of right IPL (r = - 0.27, p = 0.023) and left choroid (r = - 0.23, p = .044) in the overall sample. Thinning of right IPL and left macula were also associated with worse executive functioning (r = 0.37, p = 0.004 and r = 0.33, p = 0.009) and attention (r = 0.31, p = 0.018 and r = 0.30, p = 0.025). In patients with schizophrenia, IPL thinning was associated with increased BMI (r = - 0.44, p = 0.009) and decreased HDL levels (r = 0.43, p = 0.021). Decreased TNF-α level was related to IPL thinning, especially in the left eye (r = 0.40, p = 0.022). These findings support the hypothesis that OCT might provide the opportunity to establish an accessible and non-invasive probe of brain pathology in schizophrenia and related disorders. However, future studies investigating retinal structural changes as a biological marker for schizophrenia should also consider the metabolic state of the subjects.

Evaluating the Clinical Significance of Diazepam Binding Inhibitor in Alzheimer's Disease: A Comparison with Inflammatory, Oxidative, and Neurodegenerative Biomarkers.

INTRODUCTION: Alzheimer's disease (AD) is one of the pathologies that the scientific world is still desperate for. The aim of this study was the investigation of diazepam binding inhibitor (DBI) as a prognostic factor for AD prognosis. METHODS: A total of 120 participants were divided into 3 groups. Forty new diagnosed Alzheimer patients (NDG) who have been diagnosed but have not started AD treatment, 40 patients who diagnosed 5 years ago (D5YG), and 40 healthy control groups (CG) were included in the study. Levels of DBI, oxidative stress, inflammatory, and neurodegenerative biomarkers were compared between 3 groups. RESULTS: Plasma levels of DBI, oligomeric Aß, total tau, glial fibrillary acidic protein, α-synuclein, interleukin (IL) 1ß, IL6, tumor necrosis factor α, oxidative stress index, high-sensitive C-reactive protein, and DNA damage were found higher in D5YG and NDG as compared to CG (p < 0.001). On the contrary, plasma levels of total thiol, native thiol, vitamin D and vitamin B12 were lower in D5YG and NDG as compared to CG (p < 0.001). DISCUSSION: DBI may be a potential plasma biomarker and promising drug target for AD. It could help physicians make a comprehensive evaluation with cognitive and neurodegenerative tests.

Propolis Enhances 5-Fluorouracil Mediated Antitumor Efficacy and Reduces Side Effects in Colorectal Cancer: An in Vitro and in Vivo Study.

In this study, we investigated the combined treatment of 5-fluorouracil (5-FU) and Anatolian propolis extract (PE) on colorectal cancer (CRC)using in vitro and in vivo studies. We exposed luciferase-transfected (Lovo-Luc CRC) cells and healthy colon cells (CCD-18Co) to varying concentrations of 5-FU and PE to assess their genotoxic, apoptotic, and cytotoxic effects, as well as their intracellular reactive oxygen species (iROS) levels. We also developed a xenograft model in nude mice and evaluated the anti-tumor effects of PE and 5-FU using various methods. Our findings showed that the combination of PE and 5-FU had selectivity against cancer cells, particularly at higher doses, and enhanced the anti-tumor effectiveness of 5-FU against colon CRC. The results suggest that PE can reduce side effects and increase the effectiveness of 5-FU through iROS generation in a dose-dependent manner.

Evaluation of the relationship between pain inflammation due to dental caries and growth parameters in preschool children.

OBJECTIVES: To evaluate the relationship between pain inflammation due to dental caries and growth parameters, sleep disturbances, and oral health-related quality of life (OHRQoL) in preschool children before/after dental treatment and compare the results with the control group. MATERIALS AND METHODS: Study (pain inflammation due to caries) and control groups were included in this prospective clinical trial. The Child Sleep Habits Questionnaire (CSHQ) assessing sleep disturbances and the Early Childhood Oral Health Impact Scale (ECOHIS) assessing OHRQoL were applied in the corresponding time intervals to the study and control groups, respectively: baseline (T0study), 7 days after treatment (T1study), and following 6 months (T2study); baseline (T0control), and the following 6 months (T2control). Biochemical growth parameters (insulin-like growth factor-1 and insulin-like growth factor binding protein-3) and anthropometric measurements (standard deviation score of height, weight, and body mass index) were obtained at T0study, T2study, and T0control. Mann-Whitney U and the Student t-tests were used for statistical analyses. The significance level was set at p < 0.05. RESULTS: Data on 45 children (mean age: 55.6 ± 10.37 months) were analyzed. T2study was statistically higher than T0study for the anthropometric measurements and biochemical growth parameters (p < 0.05). T0study was statistically higher than T0control for biochemical growth parameters (p < 0.05). CSHQ and ECOHIS scores were found statistically significant at T0study than T0control (p < 0.05). Statistical scores of CSHQ and ECOHIS in T2study were significantly reduced compared to T0study (p < 0.05). CONCLUSION: Children's growth parameters, sleep disturbances, and OHRQoL improved after the elimination of pain and inflammation. CLINICAL RELEVANCE: This study's novelty is the observation of drastically increased growth parameters and reduced sleep disturbances following dental treatment.

The role of IL-6, thiol-disulfide homeostasis, and inflammatory biomarkers in the prediction of acute appendicitis in children: a controlled study.

PURPOSE: This study aimed to examine the diagnostic value of IL-6, thiol-disulfide homeostasis, complete blood count and inflammatory biomarkers in the prediction of acute appendicitis in children. METHODS: The study was designed as a prospective and controlled study in children-the study was conducted at a tertiary referential university hospital between May 2020 and April 2021. Patients were divided between study groups and one control group (CG): 1: confirmed acute appendicitis group (AAP); 2: perforated appendicitis group (PAP); and 3: non-specified abdominal pain (NAP). The age and gender of the patients were determined. The following listed laboratory parameters were compared between groups: TOS: total oxidative status, TAS: total antioxidant status, OSI: oxidative stress index, TT: total thiol, NT (µmol/L): native thiol, DIS: disulfide, IL-6: interleukin 6, TNF-a: tumor necrosis factor-alpha, WBC: white blood cell, NEU: neutrophil, NEU%: neutrophil percentage, LY: lymphocyte, LY%: lymphocyte percentage, PLT: platelet, MPV: mean platelet volume NLR: neutrophil lymphocyte ratio, CRP: C-reactive protein, LCR: lymphocyte CRP ratio, and serum lactate. RESULTS: The TOS level of the PAP group was found to be significantly higher than that in the AAP, NAP and control groups (p = 0.006, < 0.001 and p < 0.001). TAS, TT, and NT levels in the PAP group were significantly lower than those in the AAP, NAP and control groups. OSI was significantly higher in the PAP group than in the other groups. The TT and NT levels of the NAP group were both similar to those of the control group. Serum DIS level was similar between the AAP and PAP groups, AAP and NAP groups, and NAP and control groups. Serum IL-6 and TNF-α levels were found to be significantly higher in the PAP group compared to those in all groups. The WBC, NEU, and NEU% values were found to be significantly higher in the PAP group than those in the NAP and control groups, while LY and LY% values were found to be significantly lower. PAP and AAP groups were found to be similar in terms of WBC, NEU, LYM, NEU%, and LYM% values. PLT and MPV values and serum lactate values did not show a significant difference between the groups. NLR was similar in the AAP and PAP groups. A significant increase in CRP versus a decrease in LCR was detected in the PAP group compared to that in the AAP group. Multivariate analysis demonstrated that only IL-6 has significant estimated accuracy rates as 80% for the control group, 78.8% for AAP, 96.9% for PAP, and 81.6% for NAP. CONCLUSION: Rather than AAP, PAP caused significantly higher oxidative stress (increased TOS and OSI), and lower antioxidation capacity (decreased TT and NT). IL-6 levels can provide a significant stratification. Nevertheless, simply detecting WBC or CRP is not enough to distinguish the specific pathology in acute appendicitis and related conditions.

Evaluation of Oxidative Stress and Inflammatory Biomarkers Pre and Post-Treatment in New Diagnosed Atherosclerotic Patients.

Atherosclerosis is a chronic vascular inflammatory disease associated to oxidative stress and endothelial dysfunction. It is characterized by lipid accumulation in the arterial wall, increased hyperlipidemia, oxidative stress, lipid peroxidation, and protein oxidation. Our study included 45 patients ages of 40-60 and 45 healthy volunteers with similar demographic characteristics without any chronic disease as well. Fasting plasma glucose, BUN, creatinine, LDL-cholesterol, HDL-cholesterol, triglyceride, total cholesterol, HbA1c, and C-reactive protein (CRP) levels were measured using commercial kits by autoanalyzer. The oxidative stress biomarkers total oxidant status (TOS), total antioxidant status (TAS), total thiol (TT), native thiol (NT), catalase (CAT), paraoxonase (PON1), and arylesterase (ARES) enzyme activities were measured using photometric methods. The inflammatory biomarkers interleukin 1 beta (IL-1ß), tumor necrosis factor-α (TNF-α), presepsin (PSPN), and raftlin (RFTN1) levels were measured with ELISA Kits. Oxidative stress index (OSI) and disulfide (DIS) were calculated. The clinical, biochemical biomarkers such as BUN, creatinine, HDL, LDL, total cholesterol, triglyceride, and CRP levels were found to be higher than the control group and lower post-treatment compared to the pre-treatment group (p <0.001). The oxidative stress parameters, TOS, OSI, and DIS levels were found to be higher than the control group, and the levels before the treatment were statistically significantly higher than after the treatment (p < 0.001). Antioxidant biomarkers TAS, TT, and NT levels were low in the patient group. Inflammatory biomarkers were highest before treatment and decreased with treatment. Oxidative stress and inflammation, which increased in atherosclerosis patients may guide disease prognosis and treatment strategies.

Mucolytic and Antioxidant Effects of Intranasal Acetylcysteine Use on Acute Rhinosinusitis in Rats with an Acute Rhinosinusitis Model.

INTRODUCTION: The aim of this study was to investigate whether N-acetylcysteine (NAC) is effective in the treatment murine model of acute rhinosinusitis in rats. MATERIALS AND METHODS: Twelve rats were included in the study. The left nasal cavity of all rats was infected with Streptococcus pneumoniae. Group 1 was the group in which NAC was administered into the left nasal cavity twice daily. Group 2 was selected as the control group. All rats were then sterilely sacrificed under anesthesia after intracardiac blood sampling. After sacrifice, sterile culture samples were collected from the posterior nasal cavity. RESULTS: Total oxidant status and oxidative stress index (OSI), interleukin 1ß, interleukin 6, and tumor necrosis factor α levels decreased significantly in the treatment group. Total antioxidant status was significantly increased. There was a statistically significant increase in total serum thiol levels and native thiol levels. Histopathologic evaluation showed a statistically significant decrease in submucosal gland hypertrophy in the treatment group. CONCLUSION: According to our study, intranasal application of NAC can decrease the inflammatory findings in murine acute rhinosinusitis.

Evaluation of the relationship between vitamin D level and adropin, IL-1ß, IL-6, and oxidative status in women.

BACKGROUND: Vitamin D, adropin, proinflammatory cytokines, and oxidative stress closely related with metabolic homeostasis and endothelial dysfunction. The aim of the present study is to investigate how vitamin D levels affect serum adropin, IL-1ß, IL-6, and oxidative stress. METHODS: A total of 77 female subjects were divided into 3 groups according to vitamin D levels. Biochemical parameters, adropin, IL-1ß, IL-6, oxidative stress markers were studied in these groups, and the results were compared statistically. RESULTS: Serum adropin, IL-1ß, IL-6, total oxidant status (TOS) and total antioxidant status (TAS) and oxidative stress index (OSI) levels differed significantly between the vitamin D groups (p < 0.05). A significant positive correlation was detected between vitamin D, and adropin and TAS (r = 0.807; p < 0.001, r = 0.814; p < 0.001, respectively). A significant negative correlation was detected between vitamin D, and IL-1ß, IL-6, TOS, OSI (r = -0.725; p < 0.001, r = -0.720; p < 0.001, r = -0.238; p = 0.037, r = -0.705; p < 0.001, respectively). DISCUSSION: Vitamin D could show its effects through vitamin D receptors on tissues or on the ENHO gene in adropin secreting tissues via direct or indirect mechanisms. Proinflammatory cytokines, oxidative stress, and adropin targeted studies could contribute to the prevention and treatment of diseases associated with vitamin D deficiency in future.

Left lateral parietal rTMS improves cognition and modulates resting brain connectivity in patients with Alzheimer's disease: Possible role of BDNF and oxidative stress.

Repetitive Transcranial Magnetic Stimulation (rTMS) is a non-invasive neuromodulation technique which is increasingly used for cognitive impairment in Alzheimer's Disease (AD). Although rTMS has been shown to modify Brain-Derived Neurotrophic Factor (BDNF) and oxidative stress levels in many neurological and psychiatric diseases, there is still no study evaluating the relationship between memory performance, BDNF, oxidative stress, and resting brain connectivity following rTMS in Alzheimer's patients. Furthermore, there are increasing clinical data showing that the stimulation of strategic brain regions may lead to more robust improvements in memory functions compared to conventional rTMS. In this study, we aimed to evaluate the possible disease-modifying effects of rTMS on the lateral parietal cortex in AD patients who have the highest connectivity with the hippocampus. To fill the mentioned research gaps, we have evaluated the relationships between resting-state Functional Magnetic Resonance Imaging (fMRI), cognitive scores, blood BDNF levels, and total oxidative/antioxidant status to explain the therapeutic and potential disease-modifying effects of rTMS which has been applied at 20 Hz frequencies for two weeks. Our results showed significantly increased visual recognition memory functions and clock drawing test scores which were associated with elevated peripheral BDNF levels, and decreased oxidant status after two weeks of left lateral parietal TMS stimulation. Clinically our findings suggest that the left parietal region targeted rTMS application leads to significant improvement in familiarity-based cognition associated with the network connections between the left parietal region and the hippocampus.

Carotid intima-media thickness and serum proinflammatory cytokine levels in rosacea patients without cardiovascular risk factors.

There is a growing body of evidence linking rosacea to various systemic disorders, even though data regarding the association between rosacea and cardiovascular diseases are presently controversial. We sought to investigate the potential association of rosacea with subclinical atherosclerosis and serum proinflammatory/proatherogenic markers. This study included 44 patients with rosacea and 44 age-matched and sex-matched healthy control subjects. Patients with traditional cardiovascular risk factors or a history of cardiovascular events were excluded. Demographic, clinical, and laboratory data, including serum interleukin-1 beta (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and high-sensitivity C-reactive protein (hs-CRP) levels were assessed. Carotid intima-media thickness (CIMT) and carotid plaques were measured by carotid ultrasonography. Serum IL-1ß (P < .001), IL-6 (P < .001), TNF-α (P < .001), and hs-CRP (P < .001) levels were significantly higher in the patient group compared with the control group. Mean CIMT values did not differ significantly between the patient group and control group (P > .05). Patients with moderate to severe rosacea had a significantly greater CIMT than those with mild rosacea (P = .047). Rosacea patients with eye involvement had a significantly greater CIMT than those without eye involvement (P = .008). There was no significant correlation between CIMT values and inflammation parameters. As conclusion, in the absence of other traditional cardiovascular risk factors, rosacea does not seem to affect mean CIMT value. However, specific subgroups such as patients with moderate to severe disease or with eye involvement are associated with increased subclinical atherosclerosis and may require additional attention for cardiovascular disease prevention.

Circulating levels of cytokines are increased in restless legs syndrome.

BACKGROUND: Restless legs syndrome [RLS] is known as a disease of iron and dopaminergic dysregulation but inflammatory processes might also have a role in the pathogenesis. In this study, we compared the circulating levels of hsCRP, IL-1ß, IL-6, and TNF-α in patients with primary restless legs syndrome [RLS] and healthy control subjects. METHODS: We prospectively included 29 patients with primary RLS and 65 healthy controls [HC], all age-sex matched. The diagnosis of RLS was established using international guidelines. IRLSSG Severity Scale was used to evaluate the severity of RLS. Plasma levels of hsCRP, IL-1ß, IL-6, and TNF-α were measured in all participants. RESULTS: The mean age of patients was 37.8 ± 11.3 and 52% of RLS group were women. Serum IL-1ß, IL-6, and TNF-α levels of the patient group were statistically significantly higher compared to HC [p < 0.001 for all variables]. Plasma levels of hsCRP did not differ between groups. There were 8 patients with mild RLS [28%], 13 patients with moderate RLS [45%], and 8 patients with severe RLS [28%]. Only IL-6 values were significantly different between the groups. In the severe group, the value of IL-6 was significantly higher than in the other groups [p: 0.03]. CONCLUSION: These results showing higher circulating levels of inflammatory cytokines in patients with RLS support the notion that inflammation may be involved in the pathogenesis of primary RLS. However, it is necessary to perform further studies to determine if this finding is a cause or an effect.

Oxidative stress and schizophrenia: A comparative cross-sectional study of multiple oxidative markers in patients and their first-degree relatives.

OBJECTIVE: Schizophrenia (SCZ) is a chronic, disruptive mental disorder with unknown pathogenic mechanisms. Several studies evidenced that oxidative stress (OS) may be one of the causal factors to play a role in the pathophysiology of the disease. Our study aims to contribute to the SCZ research by investigating a possible relationship between the severity of illness (scored with "The Positive and Negative Syndrome Scale [PANSS]") and OS biomarkers in patients. We additionally assess the "first-degree-relatives (FDRs)" oxidative status with multiple parameters to test the idea of oxidative imbalance leads to disease progression as a genetical susceptibility factor. METHODS: This study included: 50 adult patients with SCZ, 50 unaffected FDRs, and 50 controls. OS biomarkers included myeloperoxidase (MPO), total oxidant status (TOS), total antioxidant status (TAS), total thiol (TT), native thiol (NT). Photometric methods were used to measure the parameters in the peripheral blood samples of participants. Disulphide (DS) and oxidative stress index (OSI) parameters were calculated. RESULTS: TOS, DS, OSI levels were significantly higher, and TAS, TT, NT levels were significantly lower in both SCZ and FDRs than controls. In the SCZ group, MPO activity was significantly higher compared with other groups. Results in this study did not provide a strong correlation between the PANSS and selected biomarkers. There was a slightly negative correlation between TT and PANSS in the SCZ group (P = .041, r = -.297). CONCLUSION: OS biomarkers increased significantly in the peripheral blood of SCZ patients compared with other groups indicates the presence of OS in the aetiology of the disease. Mid-levels of oxidative markers found in FDRs imply that unaffected first-degree relatives have an increased risk for turning up to the clinical presentation stage.

Urotensin-II, oxidative stress, and inflammation increase in hypertensive and resistant hypertensive patients.

Objective: Hypertension is a multi-factorial process prevalent in developed as well as in developing countries. Urotensin-II, different antioxidants, free radicals, and inflammatory biomarkers play an essential role in the cardiovascular system. The aim of this study is to investigate Urotensin-II, oxidative stress, and inflammation markers in normotensive, hypertensive, and resistant hypertensive patients. Methods: Fifty resistance hypertensive (rHT) patients, 50 hypertensive patients, and 50 age gender matched normotensive controls (NT-control) were enrolled. Urotensin-II (UII), total oxidant status (TOS), total antioxidant status (TAS), native thiol (NT), total thiol (TT), disulfide (DIS), interleukin 1 beta (IL1ß), interleukin 6 (IL6), tumor necrosis factor-alpha (TNFα), high sensitive c reactive protein (hsCRP), high-density lipoprotein (HDL) low-density lipoprotein (LDL), and total cholesterol (TC) were evaluated. Results: Serum levels of UII, IL1ß, IL6, TNFα, DIS, TOS, and OSI were found higher in rHT and HT as compared to NT-control (p < .001). On the contrary, serum levels of TT, TAS, and NT were lower in rHT and HT as compared to NT-control (p < .001). While TC, hsCRP, TOS, OSI, UII, IL1ß, IL6, and TNFα levels increase from HT to rHT group (p < .001); TAS and NT levels decrease from HT to rHT group (p < .001). Conclusions: UII levels, oxidative stress, and inflammation are higher in rHT and HT, while antioxidants and thiol levels are lower than the NT-control. Our study clearly showed that rHT and HT are more susceptible to impaired states of antioxidants, oxidative stress, and free radicals.

Are the oxidative stress levels in the tumor center and tumor boundary different from those in healthy tissue?

PURPOSE: This study aimed to investigate the relationship between oxidative stress levels in the tumor center, tumor edge, and healthy tissue. METHODS: This study included a total of 53 patients with head and neck cancer. Samples of 5 × 5 × 5 mm were collected from the tumor center, tumor edge, and the healthy tissue. Total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) values were evaluated. (1) Oxidative stress values in the center and edge of all tumors and in healthy tissues were compared according to localization. (2) Tumors were divided into two groups as malignant (Group 1 [n = 28]: Laryngeal and tongue squamous cell cancers) and benign (Group 2 [n = 25]: Pleomorphic adenoma and Warthin tumors). The groups were compared according to the localization of the tissues. RESULTS: The TOS value in the tumor edge was significantly higher than those in the tumor center and the healthy tissue. The TAS value in tissue located in the tumor edge was significantly higher than in the healthy tissue. The OSI value in the tumor edge was significantly higher than those in the tumor center and the healthy tissue. In all three localizations (tumor center, tumor edge, and healthy tissue), TOS and OSI values in Group 1 were significantly higher than Group 2. CONCLUSION: Oxidative stress values in the tumor edge are significantly higher than the center of the tumor and healthy tissue. In malignant tumors, oxidative stress values are significantly higher in all localizations compared to benign tumors.

Oxidative stress values of tumor core, edge, and healthy thyroid tissue in thyroid masses.

PURPOSE: Reactive oxygen radicals play an important role in tumor formation, progression, and invasion. In this study, the aim was to investigate the relationship between the oxidative stress values of tumor core, edge, and healthy thyroid tissue in thyroid tumors. METHODS: A total of 51 patients with thyroid tumor, 24-malignant, and 27-benign, were included in this study. Samples, measuring 5 × 5 × 5 mm, were taken from the tumor core, edge, and healthy thyroid tissue of the participants. Total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) values were examined. The oxidative stress values of core, edge, and healthy thyroid tissue of all tumors (n = 51) were compared according to the localization. The participants were divided into two groups as malignant (Group 1: Differentiated thyroid cancers) and benign (Group 2: Multinodular goiter). The groups were compared according to tissue localizations. RESULTS: The TOS value of tumor edge was significantly higher than the values of tumor core and healthy thyroid tissue. The OSI value of tumor edge was significantly higher than the values of tumor core and healthy thyroid tissue. There was no significant difference between Group 1 and Group 2 in terms of TAS, TOS, and OSI values of tumor core. The OSI values in tumor edge and healthy thyroid tissue were significantly higher in Group 1 than in Group 2. There was no significant difference between the groups in terms of TAS and TOS values of tumor edge and healthy thyroid tissue. CONCLUSION: The oxidative stress values of tumor edge were significantly higher than the tumor core and healthy thyroid tissue values. The oxidative stress values of tumor edge and healthy thyroid tissue were significantly higher in malignant thyroid tumors compared to benign thyroid tumors.

Inhibition of Carbonic Anhydrase IX Promotes Apoptosis through Intracellular pH Level Alterations in Cervical Cancer Cells.

Carbonic anhydrase IX (CAIX) is a hypoxia-related protein that plays a role in proliferation in solid tumours. However, how CAIX increases proliferation and metastasis in solid tumours is unclear. The objective of this study was to investigate how a synthetic CAIX inhibitor triggers apoptosis in the HeLa cell line. The intracellular effects of CAIX inhibition were determined with AO/EB, AnnexinV-PI, and γ-H2AX staining; measurements of intracellular pH (pHi), reactive oxygen species (ROS), and mitochondrial membrane potential (MMP); and analyses of cell cycle, apoptotic, and autophagic modulator gene expression (Bax, Bcl-2, caspase-3, caspase-8, caspase-9, caspase-12, Beclin, and LC3), caspase protein level (pro-caspase 3 and cleaved caspase-3, -8, -9), cleaved PARP activation, and CAIX protein level. Sulphonamide CAIX inhibitor E showed the lowest IC50 and the highest selectivity index in CAIX-positive HeLa cells. CAIX inhibition changed the morphology of HeLa cells and increased the ratio of apoptotic cells, dramatically disturbing the homeostasis of intracellular pHi, MMP and ROS levels. All these phenomena consequent to CA IX inhibition triggered apoptosis and autophagy in HeLa cells. Taken together, these results further endorse the previous findings that CAIX inhibitors represent an important therapeutic strategy, which is worth pursuing in different cancer types, considering that presently only one sulphonamide inhibitor, SLC-0111, has arrived in Phase Ib/II clinical trials as an antitumour/antimetastatic drug.