Current Pandemic in the World: Monkeypox from Past to Present.

Monkeypox is a zoonotic viral infection that was first identified in humans in 1970 in the Democratic Republic of Congo. The cases seen again in early May 2022 have reached 78.000 as of today. On July 23, 2022, the World Health Organization decided that the monkeypox outbreak represents a public health emergency. For the early diagnosis and effective treatment of monkeypox, inter-individual transmission routes, disease symptoms, factors affecting the course of the disease, presence of another infection, prognosis, pharmacological agents used in the prophylactic treatment, and their effects, populations at risk, waste disposal protocol should be known. For this reason, our aim is to reveal the sources of transmission of the monkeypox virus from past to present, what are the signs and symptoms in patients after infection, ways of protection from the virus, the mutation status of the virus, and treatment approaches.

Nerolidol attenuates dehydroepiandrosterone-induced polycystic ovary syndrome in rats by regulating oxidative stress and decreasing apoptosis.

AIMS: Although nerolidol (NRL) is a naturally occurring sesquiterpene alcohol with many pharmacological activities, its role in dehydroepiandrosterone DHEA-induced polycystic ovary syndrome PCOS is unknown. This study aims to explore the potential beneficial effects and underlying molecular mechanisms of nerolidol treatment on polycystic ovary syndrome. MAIN METHODS: Pre-pubertal female Sprague-Dawley rats were randomly assigned into four groups (n = 8/group); group I: control; group II: PCOS; group III: P + NRL; group IV: NRL. Biochemical parameters related to oxidative stress, inflammation, apoptosis, and hormones were estimated in the blood and ovarian tissues. Histopathological, ultrastructural, and immunohistochemical analyses were performed. Bax, P53, Cas-3, and Bcl-2 gene expression levels were detected with RT-PCR. The membrane array analysis detected chemokine, cytokine, and growth factor protein profiles. KEY FINDINGS: In light of the available data, it can deduce that nerolidol has a significant ameliorating effect on lipid peroxidation, oxidative stress, inflammation, histopathological damage, and apoptosis accompanying PCOS in female rats. SIGNIFICANCE: PCOS is not only a reproductive pathology but also a systemic condition and its etiopathogenesis is still not fully understood. Since changes in PCOS have important long-term effects on health, this study evaluated the efficacy of nerolidol, a phytotherapeutic for the control of biochemical, apoptotic, histopathological, and metabolic changes.

Protective effect of resveratrol against pembrolizumab-induced hepatotoxicity and neurotoxicity in male rats.

The present study investigates the effects of resveratrol (RSV) on brain and liver tissues in rats with pembrolizumab (PEMB)-induced toxicity. Obtained for the study were 28 male Sprague-Dawley rats (3-4 months old) which were divided into four groups: Group 1: Control. Group 2: Administered PEMB at 5 mg/kg/day i.p. for a week. Group 3: Administered RSV orally at the dose of 20 mg/kg/day for 30 days by gavage. Group 4: Administered PEMB and RSV at 20 and 5 mg/kg/day RSV, respectively, for 30 days. The results of this study revealed that PEMB leads to a significant increase in thiobarbituric acid reactive substance (TBARS) levels and a significant decrease in glutathione peroxidase (GPx), catalase (CAT), superoxide dismutase (SOD) activities, and glutathione (GSH) levels in the liver and brain tissues. The decreased SOD, CAT, GPx activities, and GSH levels increased significantly following RSV treatment in Group 4. The PEMB treatment showed histopathological alterations associated with strong positive cysteinyl aspartic acid-protease-3 (caspase-3) immunoreactivity, while RSV treatment reduced both the expression of caspase-3 protein and the histopathological changes. RSV administration prevents the biochemical, immunological, and histological alterations induced by PEMB. It can be suggested that the lower caspase-3 immunoreactivity in the PEMB + RSV group than in the PEMB group led to an inhibition of RSV on apoptosis.

Evaluation of serum neopterin, periostin, Tenascin-C, tissue inhibitor of metalloproteinase-1 and matrix metalloproteinase-2 levels in obese pregnant women

Objective: To investigate the role of extracellular matrix proteins in the molecular mechanism of inflammatory response in obese pregnant women by comparing serum levels of neopterin, periostin, Tenascin-C, tissue inhibitor of metalloproteinase-1, and matrix metalloproteinase-2 between obese and normal weight pregnant women in the third trimester. Materials and Methods: A prospective cross-sectional study was conducted between April 2021 and December 2021. A total of 84 pregnant women were included and three groups were formed with 28 participants in each group. Results: Serum levels of neopterin, periostin, Tenascin-C and tissue inhibitor of metalloproteinase-1 were significantly higher in class II-III obese pregnant women than in class I obese and normal-weight women (p=0.002, p<0.001, p<0.001, and p<0.001, respectively). There was no significant difference in serum matrix metalloproteinase-2 levels between the groups (p=0.769). Receiver operating characteristic curve analysis showed that Tenascin-C and periostin were effective in predicting pre-eclampsia [area under the curve (AUC)=0.82, 95% confidence interval (CI), 0.72-0.90, p<0.001 and AUC=0.71, 95% CI, 0.60-0.80, p=0.007, respectively]. Conclusion: This study demonstrated that class II-III obese pregnant women had significantly higher serum levels of neopterin, periostin, Tenascin-C, and tissue inhibitor of metalloproteinase-1 in the third trimester. These higher serum levels may be associated with the adverse perinatal effects of obesity during pregnancy.

18ß-glycyrrhetinic acid attenuates global cerebral ischemia/reperfusion-induced cardiac damage in C57BL/J6 mice

Abstract The aim of the present study is to investigate the cardioprotective effects of 18ß-glycyrrhetinic acid (18ß -GA) against oxidative and histological damage caused by global cerebral ischemia/ reperfusion (I/R) in C57BL/J6 mice. All male mice (n:40) were randomly divided into four groups: (1) sham-operated (Sham), (2) I/R, (3) 18ß-GA, and (4) 18ß -GA+I/R. Ischemia was not applied to the sham and 18ß-GA groups. In the I/R group, the bilateral carotid arteries were clipped for 15 min to induce ischemia, and the mice were treated with the vehicle for 10 days. In the 18ß-GA group, the mice were given 18ß-GA (100 mg/kg) for 10 days following a median incision without carotid occlusion. In the 18ß-GA+I/R group, the ischemic procedure performed to the I/R model was applied to the animals and afterwards they were intraperitoneally (i.p.) treated with 18ß-GA (100 mg/kg) for 10 days. It was found that global cerebral I/R increased TBARS levels and decreased antioxidant parameters. The 18ß-GA treatment decreased the level of TBARS and increased GSH, GPx, CAT, SOD activities. Also, the control group cardiac tissue samples were observed to have a normal histological appearance with the Hematoxylin-Eosin staining method. Histopathological damage was observed in the heart tissue samples belonging to the I/R group. The 18ß-GA treatment ameliorates oxidative and histological injury in the heart tissue after global ischemia reperfusion, and may be a beneficial alternative treatment

The usefulness of biomarkers in diagnosis of asbestos-induced malignant pleural mesothelioma.

INTRODUCTION: Malignant pleural mesothelioma (MPM) is a malignant tumor that is associated mostly with asbestos exposure. The present study was to evaluates the diagnostic value of neopterin, periostin, YKL-40, Tenascin-C (TNC), and Indolamine 2,3-dioxygenase (IDO) as noninvasive markers of malign pleural mesothelioma. METHODS: Included in the study were 30 patients diagnosed with malign pleural mesothelioma, and 25 people as a control group. Biomarker levels were determined using an enzyme immunoassay . A Mann-Whitney U test and Spearman correlation methods were used for the statistical analysis. RESULTS: All evaluated biomarkers were found to be significantly higher in the MPM group than in the control group (p < 0.05). There was no effect of such variables as gender, age or MPMsubtype on the parameters (p > 0.05) in the patient group. All biomarkers were positively correlated with each other (p < 0.001). CONCLUSIONS: The current non-invasive biomarkers that can be used in the diagnosis of MPM yielded significant results and can make important contributions to the early diagnosis of MPM.

Comparison of preoperative serum neopterin, periostin, indoleamine 2,3-dioxygenase, YKL-40, and tenascin-C levels with current tumor markers for early-stage endometrial cancer.

OBJECTIVE: To compare the predictive value of serum levels of neopterin, periostin, YKL-40, tenascin-C (TNC), and indoleamine 2,3-dioxygenase (IDO) with current tumor markers for the primary diagnosis of early-stage endometrial cancer. METHODS: A prospective cross-sectional study was conducted between January 2020 and November 2020. A total of 59 patients (38 women newly diagnosed with early-stage endometrial cancer [study group] and 21 women with benign endometrial pathologies [control group]) were enrolled. Blood samples were collected prior to surgery and underwent immunoassay analysis. RESULTS: Carcinoembryonic antigen (CEA), periostin, and IDO levels were significantly higher in the study group than the control group (P = 0.008, P = 0.034, and P = 0.003, respectively). Receiver operating characteristic curve analysis revealed that IDO, periostin, and CEA were good predictors of early-stage endometrial cancer (AUC = 0.733, 95% CI, 0.602-0.840, P < 0.002; AUC = 0.668, 95% CI, 0.533-0.785, P = 0.018; and AUC = 0.709, 95% CI, 0.576-0.820, P = 0.002, respectively). Correlation analysis revealed no significant correlation of any biomarker with age or body mass index in either the control or study group. CONCLUSION: Serum CEA, periostin, and IDO levels were significantly higher in women with endometrial cancer than in those without cancer. These results may help identify new markers for diagnosing endometrial cancer.

Relationship between guanosine triphosphate pathway and tetrahydrobiopterin in gestational diabetes mellitus.

PURPOSE: The present study assesses the change in tetrahydrobiopterin (BH4), one of the most important products in the guanosine triphosphate (GTP) pathway and in other parameters that might affect nitric oxide (NO) production, in gestational diabetes mellitus (GDM). METHODS: The study included 100 healthy pregnant women and 100 women diagnosed with GDM. Serum levels of neopterin, BH4 and NO were measured. The levels of endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS) and guanosine triphosphate cyclohydrolase I (GCHI/GTPCH) gene expression were determined. RESULTS: It was found that diabetes led to an increase in neopterin and NO levels, and a decrease in BH4 levels. A stimulation was observed in eNOS gene expression in the GDM group when compared to the control group, while GCHI levels were found to decrease when compared to the control group. iNOS gene expression was detected in neither the healthy controls nor the patient group. CONCLUSIONS: Decreased NO bioavailability plays an important role in the progression of such macrovascular diseases as diabetes. BH4 levels decrease in diabetes patients, while the increased gene expression of GCHI reverses the diabetes-related BH4 deficiency and allows the endothelial cells to regain their ability to produce NO. Since GCHI is the rate-limiting enzyme in the biosynthesis of BH4, changes in GCHI levels directly affect the BH4 levels and the NO metabolism, leading to an increased risk of macrovascular complications. The significant increase in neopterin levels suggest that this is a potential biomarker for the early diagnosis of GDM.

Clinical Significance of Increased Serum Neopterin in Chronic Kidney Failure as a Biomarker of Cell-mediated Immunity.

BACKGROUND: Neopterin is a pyrazino-pyrimidine compound which is used as a marker of cell-mediated immunity in a variety of diseases. It is known that neopterin levels increase in diseases where interferon-gamma (IFN-g) stimulation is present, and also as a result of deficiencies in renal function, given that the primary means of elimination of neopterin is through the kidneys. In this study, we aimed to investigate the role of increased neopterin levels as a prognostic biomarker in patients with impaired renal function. METHODS: A total of 90 individuals including 63 patients with chronic kidney failure (CKF) and 27 healthy volunteers were included in the study. Serum neopterin concentrations were measured using the enzyme-linked immunosorbent assay. A Mann-Whitney U test and a Pearson Correlation Test were used in the statistical analysis, with a p value of <0.05 being considered statistically significant. RESULTS: The mean age was 52.21±0.16 years in the patient group and 56.55±0.32 years in the control group. In the CKF patients, serum neopterin levels increased to a significantly greater degree than in the control group (p<0.001), while no statistically significant correlation was identified between serum neopterin levels and age (p>0.05). CONCLUSIONS: A significant increase was found in the serum neopterin levels in the CKF patients, due to both the triggering of the disease and the reduction of neopterin elimination.

Neopterin Levels and Indoleamine 2,3-Dioxygenase Activity as Biomarkers of Immune System Activation and Childhood Allergic Diseases.

BACKGROUND: Although Th2 immune activation is predominant in allergic diseases, neopterinlevels and indoleamine 2,3-dioxygenase (IDO)-1 activity (kynurenine:tryptophan ratio), which reflect Th1 immune activity, increase with interferon-gamma (IFN-γ) stimulation. We investigated neopterin, tryptophan, and kynurenine levels as biomarkersof the Th1 immune system activation and changes in IDO-1 activityin children with asthma, allergic rhinitis, and atopic dermatitis, as well as the relationship between these biomarkers and the total IgE level, age, and disease severity. METHODS: We divided 205 children (80 girls and 125 boys, four months to 17 years old) into four groups: controls, patients with asthma, patients with allergic rhinitis, and patients with atopic dermatitis. Peripheral venous blood samples were collected. Neopterin levels were determined by an enzyme immunoassay. Tryptophan and kynurenine levels were analyzed using HPLC. IDO-1 enzyme activity was calculated using tryptophan and kynurenine levels. IgE levels were measured. The Mann-Whitney U test, Kruskal-Wallis test, and Conover post-hoc method were used for statistical analysis. RESULTS: Neopterin, tryptophan, and kynurenine levels were higher and IgE levels and IDO-1 enzyme activity were lower in patients with asthma and allergic rhinitis than in controls (P<0.05). Patients with atopic dermatitis showed higher neopterin, tryptophan, and kynurenine levels, higher IDO-1 activity, and lower IgE levels thancontrols (P<0.05). CONCLUSIONS: The Th1/Th2 balance is disrupted in children with allergic diseases, concomitant with increased Th1-mediated immune response activation and reduced IgEproduction, which is promoted by Th2-type cytokines.

Protective effect of atorvastatin on oxidative stress in streptozotocin-induced diabetic rats independently their lipid-lowering effects.

In the present study, we investigate the effects of atorvastatin on the lipid profile, oxidative stress, and liver enzyme markers, and its protective activity against diabetic complications, in streptozotocin (STZ)-induced diabetic rats. Fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TC), and high-density lipoprotein (HDL) levels, as well as alanine aminotransferase (ALT) and aspartate aminotransferase (AST) enzyme activities, were measured 7 weeks after the administration of STZ and atorvastatin. Thiobarbituric acid reactive substances (TBARS), non-protein associated sulfhydryl (NP-SH), total sulfhydryl (T-SH), and nitric oxide (NO) levels were measured to evaluate oxidative stress. Atorvastatin was found to inhibit ALT and AST activities and to reduce FBG levels in rats with STZ-induced diabetes. Moreover, atorvastatin treatment significantly reduced lipid peroxidation in kidney, heart, and eye tissues (P < 0.001, for all), and resulted in a significant increase in NP-SH levels in brain tissues (P < 0.001). Total NO and nitrate levels increased significantly after atorvastatin treatment (P < 0.01). Our results revealed that atorvastatin has a protective effect against STZ-induced oxidative damage by reducing TBARS levels and increasing NP-SH levels, has a hepatoprotective effect by decreasing ALT and AST activities. It also shows the antihyperglycemic activity by lowering FBG levels.

Potential Prognostic Role of Immune System Activation Marker Neopterin in Patients with Type 2 Diabetes.

BACKGROUND: An increase in neopterin concentrations is known in some pathologies due to interferon-gamma (INF-γ) activation. These include viral and bacterial infections, auto immune diseases, metabolic diseases, psychiatric disorders, tissue and organ rejections, and different malignancies. The aim of this study was to evaluate the role of neopterin as a prognostic biomarker in type 2 diabetes, which is a metabolic disease with a high worldwide prevalence. METHODS: The study included a total of one hundred thirtynine individuals including one hundred and six patients admitted to a family medicine outpatient clinic and diagnosed with type 2 diabetes and thirty-three healthy volunteers. Serum neopterin concentrations were measured using the enzyme-linked immunosorbent assay. RESULTS: Serum neopterin levels significantly increased in type 2 diabetes patients, compared to the control group (p<0.001). CONCLUSIONS: Early diagnosis of diabetes and determination of the appropriate therapeutic options are of utmost importance, as diabetes is also associated with other systemic diseases. The risk of developing secondary diseases is high in untreated patients. Our study results suggest that serum neopterin may be a useful biomarker in patients with type 2 diabetes.

Tryptophan Degradation and Antioxidant Status in Patients With Thyroid Disorders.

BACKGROUND: The aim of this study was to evaluate the degradation of tryptophan (Trp), neopterin production and antioxidant capacity in patients with benign and malignant thyroid disease. METHODS: For this reason, the levels of tryptophan, kynurenine (Kyn) and neopterin, and superoxide dismutase (SOD) and catalase (CAT) enzyme activities in 67 thyroid patients were evaluated in our study and the results were compared with 30 healthy controls. RESULTS: Tryptophan and kynurenine levels in thyroid patients decreased compared to the control group. Patients with thyroid disease had lower CAT activity than the control group. The neopterin and tryptophan levels in malignant and benign patients were also significantly different. CONCLUSION: The results of the present study suggest that thyroid disorders may lead to changes in tryptophan degradation, neopterin production and CAT enzyme activities.

Inhibition of cell proliferation, migration and colony formation of LS174T Cells by carbonic anhydrase inhibitor.

BACKGROUND: Metastasis is the leading cause of cancer deaths. Migration of tumor cells is an important stage in metastasis. Therefore, recent studies have focused on clarifying migration and migration-dependent cell functions such as angiogenesis, wound healing, and invasion. OBJECTIVES: In the present study, we aimed to investigate the effect of acetazolamide, which is a classical carbonic anhydrase inhibitor, on the cell viability, migration, and colony forming capacity of human LS174T colorectal cancer cells. METHODS: Three different cell culture techniques (MTT test, wound healing and clonogenic assay) were performed in this in vitro study on colorectal cancer cells. RESULTS: Acetazolamide reduced the cell viability, migration and colony formation ability of cells depending on dose. There was no significant difference between the cells treated with acetazolamide with 1 µM dose and the control. However, it can be concluded that acetazolamide exerts its effect on human colorectal cancer cells at 10-1000 µM concentrations. CONCLUSION: Acetazolamide was observed to significantly inhibit the cell viability, colony forming capacity, and migration ability in the culture medium of LS174T cells. This inhibitor effect of acetazolamide was observed to be dependent on the concentration in medium.

Synthesis of 3,6-disubstituted 7H-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazines as novel analgesic/anti-inflammatory compounds.

In this study, a new class of 4-amino-3-substituted-1,2,4-triazole-5-thiones (1-4) and their corresponding condensed derivatives 3,6-disubstituted 7H-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazines (1a-4c) were synthesized and evaluated for their analgesic/anti-inflammatory activities. All synthesized compounds were also tested for their gastric toxicity and antioxidant activity on acute administration. Most of the compounds showed significant activity in both carrageenan-induced oedema and acetic acid-induced writhing tests besides negligible gastrointestinal toxicity. The compounds showing less ulcerogenic effect also showed less lipid peroxidation (LPO) level. Most promising results were obtained with the compounds that placed a fluoro or a chloride on the phenyl ring at the sixth position of the fused ring.

Synthesis and characterization of some new 2(3H)-benzoxazolones with analgesic and antiinflammatory activities.

The synthesis, characterization and pharmacological activities of a new series of (6-difluorobenzoyl)-5-methyl-3-benzoylmethyl-2(3H)-benzoxazolone and 5-methyl-3-(2-hydroxyl-2-phenylethyl)-2(3H)-benzoxazolone are described. Antiinflammatory activity was investigated by the carrageenin-induced paw oedema test and analgesic activity by acetic acid writhing and hot plate tests in mice. Among the synthesized compounds, compound 3e 6-(2,5-difluorobenzoyl)-3-(4-bromobenzoylmethyl-2(3H)-benzoxazolone was found to be the most promising compound for analgesic activity. Reduced compounds (4a-4d) displayed considerable anti-inflammatory activity compared to the other derivatives.