The role of oxidative stress and inflammation biomarkers in pre- and postoperative monitoring of prostate cancer patients.

INTRODUCTION: Prostate Cancer (PC) is a global health concern affecting men worldwide. Oxidative stress is believed to contribute to the initiation of early-stage PC lesions. Additionally, inflammation has long been acknowledged as a factor in the development of PC. We aimed to examine the biomarkers of oxidative stress and inflammation in PC patients before and after surgery. PATIENTS AND METHODS: A cross-sectional study was conducted at the Urology Outpatient Clinic of Bezmialem Vakif University Hospital. A total of 150 individuals were included in the study, divided into five groups: 50 Healthy controls, 25 patients with Benign Prostatic Hyperplasia (BPH), 25 patients with Low-Risk Prostate Cancer (LRPC), 25 patients with Medium-Risk Prostate Cancer (MRPC), and 25 patients with High-Risk Prostate Cancer (HRPC). Measurements of Total Oxidant Status (TOS), Total Antioxidant Status (TAS), Total Thiol (TT), and Native Thiol (NT) were performed using photometric methods. Oxidative Stress Index (OSI) and Disulfide (DIS) levels were calculated mathematically. Levels of Interleukin-10 (IL-10), Interleukin-1beta (IL-1ß), Tumor Necrosis Factor-alpha (TNF-α), Interleukin-6 (IL-6), and Presepsin were determined using commercially available enzyme-linked immunosorbent assay (ELISA) kits. RESULTS: Compared to the healthy control group, the results indicated a statistically significant increase in both oxidative stress and inflammation levels. In the groups receiving both pharmaceutical therapy and surgical treatment (PC), a significant decrease in oxidative stress and inflammation levels was observed. CONCLUSION: Consequently, it is suggested that the assessment of oxidative stress and inflammatory biomarkers should be incorporated in the pre- and postoperative monitoring of patients with PC.

Total Antioxidant Status (TAS) levels are found to be statistically lower in all PC groups, indicating a correlation between oxidative stress and the progression of PC.Levels of inflammatory biomarkers (IL-1ß, IL-6, IL-10, TNF-α) were found to be higher before and after surgery in PC groups, and their variation correlated with tumor grade and size.Post-surgery, a decrease in presepsin levels is associated with a reduced likelihood of sepsis in PC patients.Reductions in oxidative stress and inflammation levels postoperatively suggest the effectiveness of surgical intervention in mitigating these factors.The potential for personalized medicine to decrease PC mortality is highlighted by better understanding the functional relationship coordinating inflammatory signatures in the tumor microenvironment.

Effective Anticancer Potential of a New Sulfonamide as a Carbonic Anhydrase IX Inhibitor Against Aggressive Tumors.

This study examines efficiency of a newly synthesized sulfonamide derivative 2-bromo-N-(4-sulfamoylphenyl)propanamide (MMH-1) on the inhibition of Carbonic Anhydrase IX (CA IX), which is overexpressed in many solid tumors including breast cancer. The inhibitory potential of MMH-1 compound against its four major isoforms, including cytosolic isoforms hCA I and II, as well as tumor-associated membrane-bound isoforms hCA IX and XII, was evaluated. To this context, the cytotoxic effect of MMH-1 on cancer and normal cells was tested and found to selectively affect MDA-MB-231 cells. MMH-1 reduced cell proliferation by holding cells in the G0/G1 phase (72 %) and slowed the cells' wound healing capacity. MMH-1 inhibited CA IX under both hypoxic and normoxic conditions and altered the morphology of triple negative breast cancer cells. In MDA-MB-231 cells, inhibition of CA IX was accompanied by a decrease in extracellular pH acidity (7.2), disruption of mitochondrial membrane integrity (80 %), an increase in reactive oxygen levels (25 %), and the triggering of apoptosis (40 %). In addition, the caspase cascade (CASP-3, -8, -9) was activated in MDA-MB-231 cells, triggering both the extrinsic and intrinsic apoptotic pathways. The expression of pro-apoptotic regulatory proteins (Bad, Bax, Bid, Bim, Cyt-c, Fas, FasL, TNF-a, TNF-R1, HTRA, SMAC, Casp-3, -8, P21, P27, and P53) was increased, while the expression of anti-apoptotic proteins, apoptosis inhibitor proteins (IAPs), and heat shock proteins (HSPs) (Bcl-2, Bcl-w, cIAP-2, HSP27, HSP60, HSP70, Survivin, Livin, and XIAP) was decreased. These results propose that the MMH-1 compound could triggers apoptosis in MDA-MB-231 cells via the pH/MMP/ROS pathway through the inhibition of CA IX. This compound is thought to have high potential and promising anticancer properties in the treatment of aggressive tumors.

The Design and Optimization of Ceramide NP-Loaded Liposomes to Restore the Skin Barrier.

The impairment of skin integrity derived from derangement of the orthorhombic lateral organization is mainly caused by dysregulation of ceramide amounts in the skin barrier. Ceramides, fatty acids, and cholesterol-containing nano-based formulations have been used to impair the skin barrier. However, there is still a challenge to formulate novel formulations consisting of ceramides due to their chemical structure, poor aqueous solubility, and high molecular weight. In this study, the design and optimization of Ceramide 3 (CER-NP)-loaded liposomes are implemented based on response surface methodology (RSM). The optimum CER-NP-loaded liposome was selected based on its particle size (PS) and polydispersity index (PDI). The optimum CER-NP-loaded liposome was imagined by observing the encapsulation by using a confocal laser scanning microscope (CLSM) within fluorescently labeled CER-NP. The characteristic liquid crystalline phase and lipid chain conformation of CER-NP-loaded liposomes were determined using attenuated total reflectance infrared spectroscopy (ATR-IR). The CER-NP-loaded liposomes were imagined using a field emission scanning electron microscope (FE-SEM). Finally, the in vitro release of CER-NP from liposomes was examined using modified Franz Cells. The experimental and predicted results were well correlated. The CLSM images of optimized liposomes were conformable with the other studies, and the encapsulation efficiency of CER-NP was 93.84 ± 0.87%. ATR-IR analysis supported the characteristics of the CER-NP-loaded liposome. In addition, the lipid chain conformation shows similarity with skin barrier lipid organization. The release pattern of CER-NP liposomes was fitted with the Korsmeyer-Peppas model. The cytotoxicity studies carried out on HaCaT keratinocytes supported the idea that the liposomes for topical administration of CER-NP could be considered relatively safe. In conclusion, the optimized CER-NP-loaded liposomes could have the potential to restore the skin barrier function.

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.

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.

Comparison of Possible Changes in Oxidative Stress, DNA Damage, and Inflammatory Markers in Children/Adolescents Diagnosed with Sluggish Cognitive Tempo and Children/Adolescents Diagnosed with Attention-Deficit/Hyperactivity Disorder.

Background: There has been a debate on whether sluggish cognitive tempo (SCT) differs from attention-deficit/hyperactivity disorder (ADHD). Although there have been many studies on metabolic parameters in relation to ADHD, no similar studies have been conducted on patients with SCT. We investigated whether there are differences between SCT and ADHD in terms of these factors. Subjects and Methods: Sixty-two participants with ages ranging from 11 to 18 who have diagnosis of ADHD (33 subjects) and SCT (29 subjects) were included in this study. The parents of all participants completed the 48-item Conners' Parent Rating Scale (CPRS) and the Barkley Child Attention Scale (BCAS) forms, and all participants' blood was taken to compare metabolic, oxidative stress, and antioxidant status of the SCT and ADHD groups. A child and adolescent psychiatrist interviewed the parents and children to assess the diagnosis of SCT and ADHD using standard diagnostic procedures. Results: In the comparison between the SCT and ADHD groups in terms of metabolic parameters, statistically significant differences were found in terms of total oxidant status, total antioxidant status, Oxidative Stress Index, total thiol, native thiol, disulfide, interleukin (IL)-1ß, IL-6, and DNA damage (p < 0.05), but not in terms of tumor necrosis factor-α (p > 0.05). Conclusions: Our data showed that these two disorders may be different, but we believe that the data that indicate their differences remain inconclusive overall, but this study may be a potential pathway for future research.

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.

Oxidative stress, DNA damage, and inflammation in COVID-19 patients.

OBJECTIVE: Severe inflammation and oxidative stress seen in COVID-19 patients cause cumulative antiviral effects, and serious inflammation increases tissue, oxidative damage, and DNA damage. Therefore, in this study, oxidative stress, DNA damage, and inflammation biomarkers were investigated in patients diagnosed with COVID-19. METHODS: In this study, blood samples were obtained from 150 Covid-19 patients diagnosed by polymerase chain reaction and 150 healthy volunteers with the same demographic characteristics. Total oxidant status (TOS), total antioxidant status (TAS), total thiol (TT), native thiol, and myeloperoxidase (MPO) activities were measured by photometric methods. The levels of tumor necrosis factor-alpha (TNF-α), interleukin 1 beta (IL-1ß), and interleukin 6 (IL-6), which are inflammation markers, were measured by the ELISA method using commercial kits. The genotoxic effect was evaluated by Comet Assay. RESULTS: The oxidative stress biomarkers; Disulfide, TOS, MPO, oxidative stress index, and IL-1ß, IL-6, and TNF-α levels of inflammation biomarkers and the DNA damage in COVID-19 patients were increased (p<0.001), and the levels of TAS, TT, and NT In COVID-19 patients were decreased (p<0.001). CONCLUSION: In COVID-19 patients, induced DNA damage, inflammation, and oxidative stress can guide the prognosis and treatment strategies of the disease.

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.

Endocan: A novel biomarker of endothelial dysfunction in depression?

Endocan is a proteoglycan secreted from endothelium upon endothelial damage. Since depression is associated with higher inflammation and oxidative stress to the vascular endothelium, endothelial dysfunction is prevalent and it is one of the responsible mechanisms for increased cardiovascular morbidity and mortality in depressive disorders. This study aimed to investigate endocan levels in patients with depression (either bipolar or unipolar) and healthy controls to evaluate the projected endothelial injury. We included nonsmoker patients without comorbid inflammatory conditions: 31 with Bipolar Disorder Depression (BDD), 30 with Major Depressive Disorder (MDD) and 25 healthy controls (HC). The severity of depression was assessed with the Hamilton Depression Rating Scale (HDRS). Ultimately, serum endocan levels were significantly higher in patients with BDD than in patients with MDD (p < .000) and HCs (p < .000). Also, patients with MDD had significantly higher endocan levels than HCs (p < .000). The AUC value for the endocan to differentiate patients with depression from controls was 0.990 (95% CI: 0.971-1.000; p < .001) with sensitivity and specificity of 98.4 and 100%, respectively, and an optimal cut-off value of 316.92 ng/L. Serum endocan levels showed a mild positive correlation with HDRS scores (r = 0.372, p = .039) in the BDD group but not in the MDD group (r = -0.242, p = .20). Patients with BDD had higher endocan levels than MDD; this finding, while preliminary, could be an implication of higher endothelial dysfunction in BDD.

Synthesised thymoquinone-oxime induces cytotoxicity, genotoxicity and apoptosis in hepatocellular cancer cells: in vitro study.

Hepatocellular carcinoma is the most common primary malignant tumor of the liver, and its incidence is increasing worldwide. There is a need to develop new therapeutic strategies to treat the disease. In this study, we synthesised the oxime derivative of thymoquinone and investigated cytotoxicity, genotoxicity, and apoptosis in hepatocellular cancer cells. The synthesised thymoquinone-oxime structure was confirmed by NMR. After incubating the hepatocellular cancer cell line for 24 h, the cytotoxicity ATP by luminometric, intracellular reactive oxygen species, and intracellular calcium by fluorometric. The mitochondrial membrane potential was determined by flow cytometry. DNA damage by alkaline single-cell gel electrophoresis, and apoptosis damage by acridine orange/ethidium bromide double dye method. Concentrations of thymoquinone-oxime statistically increased cytotoxicity, intracellular reactive oxygen species, intracellular calcium, apoptosis, and DNA damage in a concentration-dependent manner. Mitochondrial membrane potential and glutathione levels are also decreased. These findings show that thymoquinone-oxime has an anti-tumor effect on hepatocellular carcinoma cells.

Among many herbs, Black seed (Nigella sativa) belonging to the Ranunculaceae family has been recognised worldwide as one of the most valuable nutrient-rich herbsThere is no relevant data on the effect of the newly synthesised oxime derivative of TQ (TQ-ox) in cancer cells HEP-G2A new TQ derivative has a higher anti-tumor effect on hepatocellular carcinoma.

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.

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.

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.

Oxidative and Inflammatory Parameters in Children and Adolescents With ADHD.

OBJECTIVE: This study aims that oxidative stress and inflammation status in children and adolescents with attention deficit hyperactivity disorder (ADHD) compared to their healthy peers. METHOD: Thirty ADHD and healthy controls were included in this study. ADHD diagnosis according to the DSM-V and Conners' teacher and parent rating scale by a structured psychiatric interview. Total oxidant status (TOS), total antioxidant status (TAS), and total and native thiol levels were determined using photometric methods. Presepsin, Interleukin (IL) 1-ß, IL-6, and Tumor Necrosis Factor-alpha (TNF-α) levels were measured with commercial ELISA kits. RESULTS: We showed that TOS and oxidative stress index were significantly higher in the ADHD group, and TAS was lower than in the control group (p<.001). Similarly, IL1-ß, IL-6, and TNF-α levels were statistically higher in the ADHD group. Backward LR regression analysis reveals that TOS and IL-6 predicted ADHD. CONCLUSION: TOS and IL-6 levels may play a role in the pathogenesis of ADHD.

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.

Oxidative Stress Level in Patients with Subarachnoid Hemorrhage.

BACKGROUND: One of the antioxidant mechanisms is the dynamic balance between thiol and disulfide, which, in subarachnoid hemorrhage and other chronic diseases, is disrupted in favor of the latter. The two most commonly used oxidative stress (OS) biochemical markers are the oxidative stress index (OSI) value, which indicates the total oxidant status (TOS) and total antioxidant status (TAS) balance, and the thiol-disulfide (TDS) value, which indicates the total thiol (TT) and native thiol (NT) balance. High OS levels require further investigations. We aimed to investigate the OS level in aneurysmal SAH (aSAH) patients. METHODS: In this clinical prospective study, blood samples were collected from 50 consecutively treated patients with aSAH and 50 volunteers. Serum TOS, TAS, TT, and NT levels were measured using Erel's method via a spectrophotometer. The Glasgow Coma Scale (GCS) scores, Fisher grades, length of hospital stay (LOS), and the Glasgow Outcome Scale (GOS) scores were recorded. Consequently, the OSI and TDS values were calculated in all participants. RESULTS: A statistically significant difference was observed in the TAS, TOS, OSI, and TDS values between the aSAH patients and the controls. The TT and NT values were significantly lower in aSAH patients than in the controls. A correlation was identified between the OSI values and the GCS scores. Although a correlation was observed between the TDS values and the LOS, no correlation was found between the OSI and the TDS values. CONCLUSION: The OSI and TDS, which are OS indicators, might serve as the additional objective nominal data to evaluate the treatment efficacy and follow-up for SAH patients. Moreover, decreasing the OSI values and increasing the TT values can be used as improvement indicators in the treated aSAH patients. If we can reduce the OS at the early stage of SAH, it could improve the prognosis by reducing both the morbidity and mortality rates. Further randomized investigations are required to prove the findings in this prospective study.

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.

TQ-Ox, a novel synthetic derivative of thymoquinone on ovarian cancer cells in vitro.

There are many studies in the literature on thymoquinone (TQ)-related cancer cells and models, and there is no relevant study investigating the efficacy of the oxime derivative of TQ (TQ-Ox). This study synthesized TQ-Ox and examined its cytotoxic, genotoxic and apoptotic properties in ovarian cancer cells. The structure TQ-Ox was confirmed with NMR. The cytotoxicity by luminometric ATP, intracellular reactive oxygen species (iROS) by fluorometric, intracellular calcium (iCa2+) by fluorometric, mitochondrial membrane potential (MMP) by flow cytometry, glutathione (GSH) levels with GSH/GSSG-Glo assay, DNA damage by comet assay, and apoptosis by acridine orange/ethidium bromide dye were determined. Concentrations of TQ-Ox were statistically increased cytotoxicity, DNA damage, apoptosis, iROS, and iCa2+ in a concentration-dependent manner (p < 0.001). Besides, MMP and GSH levels also decreased statistically significantly (p < 0.001) with increasing concentrations. TQ-Ox would be an effective treatment option by increasing cytotoxicity, genotoxicity, and apoptosis in ovarian carcinoma.

Beneficial effects of vitamin B12 treatment in pediatric patients diagnosed with vitamin B12 deficiency regarding total-native thiol, oxidative stress, and mononuclear leukocyte DNA damage.

Vitamin B12 is involved in biochemical metabolic pathways. B12 deficiency is common in childhood when the need for the vitamin increases and growth and development occur. Various hematological, neurological, psychiatric, and gastrointestinal disorders are observed in its deficiency. In addition, B12 deficiency is associated with oxidative stress and DNA damage. Therefore, the aim of our study is to evaluate oxidative stress, thiol/disulfide homeostasis, and DNA damage pre and post-treatment in children diagnosed with B12 deficiency. A total of 40 children with B12 deficiency were included in the study after the consent form was approved. Blood was drawn from children pre and posttreatment. Hemoglobin (HGB), hematocrit (HCT), and red blood cells (RBC) were measured by autoanalyzer; total antioxidant status (TAS), total oxidant status (TOS), total thiol (TT), and native thiol (NT) were measured by the photometric method, and DNA damage was analyzed by the comet assay method. Oxidative stress index (OSI) and disulfide (DIS) values were calculated. As a result of the experiments, HGB, HCT, and RBC increased with treatment. While TAS, TT, and NT as antioxidant parameters increased; TOS, OSI, and DIS decreased with treatment compared to pretreatment. DNA damage was also found to decrease with treatment. Additionally, these data were statistically significant (p < 0.001). It was found that oxidative stress and DNA damage decreased with oral B12 treatment in children with B12 deficiency, and clinical parameters were also improved.