Oxidative stress and antioxidant status in threatened preterm labor.

PURPOSE: The purpose of this study was the evaluation of total oxidant status (TOS), total antioxidant status (TAS), oxidative stress index (OSI) and superoxide dismutase (SOD) levels in women with threatened preterm labor (TPL) and also to compare the levels of these oxidative stress biomarkers of TPL pregnancies that had preterm and term deliveries. METHODS: This case-control study was conducted on 46 patients diagnosed with TPL and 47 healthy pregnant women matched for gestational age. Patients with threatened preterm labor were divided into two groups: true preterm birth (TPB) group (n = 16) and false preterm birth (FPB) group (n = 30) groups. Maternal serum SOD, TOS and TAS levels were measured by a spectrophotometric method using a commertial kit. OSI level for each patient was calculated by using the formula: (TOS (µmol·H2O2·equiv/L) × 100)/(TAS (µmol·Trolox·equiv/L)). RESULTS: The mean TAS levels of the TPB and FPB groups were significantly lower than those of the control group (0.96 ± 0.3 vs 1.36 ± 0.34, p1 < 0.001; 0.97 ± 0.22 vs 1.36 ± 0.34, p2 < 0.001, respectively). The mean SOD, TOS and OSI levels of the TPB and FPB groups were significantly higher than those of the control group (p < 0.001). There was no significant difference between the TPB and FPB groups for any oxidative stress biomarkers. CONCLUSION: The maternal serum oxidative stress biomarkers are increased in pregnancies with TPL. However, these are not effective in predicting preterm birth in pregnancies with TPL.

The Novel 5-Fluorouracil Loaded Ruthenium-based Nanocarriers Enhanced Anticancer and Apoptotic Efficiency while Reducing Multidrug Resistance in Colorectal Cancer Cells.

Recently, nanocarriers have been made to eliminate the disadvantages of chemotherapeutic agents by nanocarriers. Nanocarriers show their efficacy through their targeted and controlled release. In this study, 5-fluorouracil (5FU) was loaded into ruthenium (Ru)-based nanocarrier (5FU-RuNPs) for the first time to eliminate the disadvantages of 5FU, and its cytotoxic and apoptotic effects on HCT116 colorectal cancer cells were compared with free 5FU. 5FU-RuNPs with a size of approximately 100 nm showed a 2.61-fold higher cytotoxic effect compared to free 5FU. Apoptotic cells were detected by Hoechst/propidium iodide double staining, and the expression levels of BAX/Bcl-2 and p53 proteins, in which apoptosis occurred intrinsically, were revealed. In addition, 5FU-RuNPs was also found to reduce multidrug resistance (MDR) according to BCRP/ABCG2 gene expression levels. When all the results were evaluated, the fact that Ru-based nanocarriers alone did not cause cytotoxicity proved that they were ideal nanocarriers. Moreover, 5FU-RuNPs did not show any significant effect on the cell viability of normal human epithelial cell lines BEAS-2B. Consequently, the 5FU-RuNPs synthesized for the first time may be ideal candidates for cancer treatment because they can minimize the potential drawbacks of free 5FU.

Increased levels of nerve growth factor accompany oxidative load in recurrent pregnancy loss. Machine learning applied to FT-Raman spectra study.

The presented article is focused on developing and validating an efficient, credible, minimally invasive technique based on spectral signatures of blood serum samples in patients with diagnosed recurrent pregnancy loss (RPL) versus healthy individuals who were followed at the Gynecology department. A total of 120 participants, RPL disease (n = 60) and healthy individuals (n = 60), participated in the study. First, we investigated the effect of circulating nerve growth factor (NGF) in RPL and healthy groups. To show NGF's effect, we measured the level of oxidative loads such as Total Antioxidant Level (TAS), Total Oxidant Level (TOS), and Oxidative Stress Index (OSI) with Beckman Coulter AU system and biochemical assays. We find a correlation between oxidative load and NGF level. Oxidative load mainly causes structural changes in the blood. Therefore, we obtained Raman measurements of the participant's serum. Then we selected two Raman regions, 800 and 1800 cm-1, and between 2700 cm-1 and 3000 cm-1, to see chemical changes. We noted that Raman spectra obtained for RPL and healthy women differed. The findings confirm that the imbalance between reactive oxygen species and antioxidants has important implications for the pathogenesis of RPL and that NGF levels accompany the level of oxidative load in the RPL state. Biomolecular structure and composition were determined using Raman spectroscopy and machine learning methods, and the correlation of these parameters was studied alongside machine learning technologies to advance toward clinical translation. Here we determined and validated the development of instrumentation for the Analysis of RPL patients' serum that can differentiate from control individuals with an accuracy of 100% using the Raman region corresponding to structural changes. Furthermore, this study found a correlation between traditional biochemical parameters and Raman data. This suggests that Raman spectroscopy is a sensitive tool for detecting biochemical changes in serum caused by RPL or other diseases.

Association between Serum Galectin-3 and Growth Differentiation Factor-15 Levels and Coronary Slow Flow Phenomenon.

Background: Coronary slow flow phenomenon (CSFP) is characterized by delay in the progression of contrast material in the coronary tree that is not accompanied by significant coronary artery narrowing. Pathophysiologic pathways underpinning CSFP still remain poorly understood. Objectives: To evaluate the relationship between serum galectin-3 (GAL-3) and growth differentiation factor-15 (GDF-15) levels with CSFP. Methods: Fifty CSFP patients and 40 subjects with normal coronary arteries were included in this retrospective study. The patients' serum GDF-15 and GAL-3 concentration levels were measured using relevant kits. Thrombolysis in myocardial infarction frame count (TFC) of each patients was determined. Results: We did not find any differences with respect to clinical and demographic features between the two groups. GDF-15 and GAL-3 concentration levels were significantly higher in the patients with CSFP. Moreover GDF-15 and GAL-3 concentration levels were positively correlated with TFC (GDF-15; r = 0.448, GAL-3; r = 0.642, p < 0.001 for both). Multivariate logistic regression showed that GAL-3 and GDF-15 were predictors of the CSFP. Similarly, GDF-15 and GAL-3 were the only predictors of TFC. More specifically, GDF-15 and GAL-3 concentration levels of 182.18 pg/mL and 8.58 ng/mL predicted CSFP with sensitivities of 76% and 87.5%, respectively, and specificities of 84% and 75%, respectively. Conclusions: GDF-15 and GAL-3 levels were increased in the CSFP patients and predicted the presence and severity of CSFP. Thus, these two biomarkers might prove useful in relation to the diagnosis of CSFP.

Blood serum lipid profiling may improve the management of recurrent miscarriage: a combination of machine learning of mid-infrared spectra and biochemical assays.

The present article is focused on developing and validating an efficient, credible, minimally invasive technique based on spectral signatures of blood samples of women with recurrent miscarriage vs. those of healthy individuals who were followed in the Department of Obstetrics and Gynecology for 2 years. For this purpose, blood samples from a total of 120 participants, including healthy women (n=60) and women with diagnosed recurrent miscarriage (n=60), were obtained. The lipid profile (high-density lipoprotein, low-density lipoprotein, triglyceride, and total cholesterol levels) and lipid peroxidation (malondialdehyde and glutathione levels) were evaluated with a Beckman Coulter analyzer system for chemical analysis. Biomolecular structure and composition were determined using an attenuated total reflectance sampling methodology with Fourier transform infrared spectroscopy alongside machine learning technology to advance toward clinical translation. Here, we developed and validated instrumentation for the analysis of recurrent miscarriage patient serum that was able to differentiate recurrent miscarriage and control patients with an accuracy of 100% using a Fourier transform infrared region corresponding to lipids. We found that predictors of lipid profile abnormalities in maternal serum could significantly improve this patient pathway. The study also presents preliminary results from the first prospective clinical validation study of its kind.

Prediction of preterm delivery in threatened preterm labour with short cervical length.

In this study, we evaluated the value of the uterocervical angle (UCA), myometrial thickness (MT), sICAM-1, sVCAM-1, soluble E-selectin (sE-selectin) and pentraxin 3 (PTX3) levels in women with threatened preterm labour (TPL) in predicting spontaneous preterm birth (sPTB) within 14 days in symptomatic women with cervical length (CL) measurements between 10 and 25 mm. Forty-six patients diagnosed with TPL, 47 healthy pregnant women were evaluated in a case-control study. sE-selectin (AUC = 0.744, p = .007) and PTX3 (AUC = 0.711, p = .019) were found to be effective in predicting preterm delivery within 14 days. In conclusion, maternal sE-selectin and PTX3 levels may be helpful in identifying pregnancies that will deliver within 14 days in symptomatic women with CL measurements between 10 and 25 mm. However, maternal sICAM-1 and sVCAM-1 levels, MT and UCA are not effective in the prediction of sPTB in TPL pregnancies. Impact StatementWhat is already known on this subject? Aetiology of spontaneous preterm birth (sPTB) is unclear and believed to be multifactorial, infection, inflammation, vascular endothelial dysfunction and uteroplacental ischaemia are all considered to be related to preterm delivery syndrome. Transvaginal cervical length (CL) measurement is a good indicator of increased risk of sPTB. Inflammation is accepted to have a central role in the process of labour.What do the results of this study add? soluble E-selectin (sE-selectin) and pentraxin 3 (PTX3) levels may be helpful in identifying pregnancies that will deliver within 14 days in symptomatic women with CL measurements between 10 and 25 mm.What are the implications of these findings for clinical practice and/or further research? This study will help understand the important role of the inflammatory process in predicting spontaneous preterm birth.

Serum catestatin level is increased in women with preeclampsia.

Catestatin can inhibit catecholamine release from chromaffin cells and adrenergic neurons. Catestatin can also have a strong vasodilator effect. This may be useful in understanding the pathophysiology of preeclampsia and its treatment. In this study, we investigated the serum catestatin levels in pregnant women with and without preeclampsia. Fifty consecutive women with mild preeclampsia, 50 consecutive women with severe preeclampsia, and 100 consecutive pregnant women with a gestational age-matched (±1 week) uncomplicated pregnancy were evaluated in a cross-sectional study. Mean serum catestatin was significantly increased in the preeclampsia group compared to the control group (290.7 ± 95.5 pg/mL vs. 182.8 ± 72.0 pg/mL). Mean serum catestatin was comparable in mild and severe preeclampsia groups (282.7 ± 97.9 pg/mL vs. 298.7 ± 93.4 pg/mL, p = .431). Serum catestatin levels had positive correlations with systolic and diastolic blood pressure, urea, uric acid, and creatinine. In conclusion, serum catestatin levels are increased in preeclamptic pregnancies compared to gestational age-matched controls.IMPACT STATEMENTWhat is already known on this subject? The role of autonomic nervous system dysregulation in the pathophysiology of preeclampsia is known. The most obvious part of this dysregulation is the sympathetic nervous system activation. The adrenal medulla is one of the locations of the sympathetic nervous system in the body.What do the results of this study add? Serum catestatin levels were found to be correlated with clinical and laboratory data of preeclampsia. This highlights the importance of chromaffin cell secretions in the adrenal medulla in preeclampsia.What are the implications of these findings for clinical practice and/or further research? This study will help understand the role of the adrenal medulla in the autonomic nervous system dysregulation in preeclampsia. Also, control of serum catestatin levels may support the treatment of hypertension in preeclampsia.

Serum Vasostatin-1 Level is Increased in Women with Preeclampsia.

OBJECTIVE: To evaluate the serum vasostatin-1 levels in preeclamptic and non-preeclamptic pregnant women. MATERIALS AND METHODS: Thirty consecutive women with mild preeclampsia and sixty consecutive women with severe preeclampsia were compared with ninety gestational age-matched (±1 week) non-preeclamptic pregnant women with an appropriate-for-gestational-age (AGA) fetus. RESULTS: Mean serum vasostatin-1 was significantly higher in women with preeclampsia than gestational age-matched controls. Mean serum vasostatin-1 was significantly higher in the mild preeclampsia group compared to its gestational age-matched control group, and in the severe preeclampsia group compared to its gestational age-matched control group. There was no significant difference in mean serum vasostatin-1 levels between the mild and severe preeclampsia groups, and in severe early- and severe late-onset preeclampsia groups. Serum vasostatin-1 had positive correlations with systolic and diastolic blood pressure. CONCLUSION: Serum vasostatin-1 was significantly higher in women with preeclampsia compared to those of the gestational age-matched controls. There was no significant difference in mean serum vasostatin-1 levels between the mild and severe preeclampsia groups and severe early- and severe late-onset preeclampsia groups.

Structural insights into the NAD+-dependent formate dehydrogenase mechanism revealed from the NADH complex and the formate NAD+ ternary complex of the Chaetomium thermophilum enzyme.

The removal of carbon dioxide from the waste streams of industrial processes is a major challenge for creation of a sustainable circular economy. This makes the synthesis of formate from CO2 by NAD+ dependent formate dehydrogenases (FDHs) an attractive process for this purpose. The efficiency of this reaction is however low and to achieve a viable industrial process an optimised engineered enzyme needs to be developed. In order to understand the detailed enzymatic mechanism of catalysis structures of different cofactor and substrate complexes of the FDH from the thermophilic filamentous fungus, Chaetomium thermophilum have been determined to 1.2-1.3 Å resolution. The substrate formate is shown to be held by four hydrogen bonds in the FDH catalytic site within the ternary complex with substrate and NAD+and a secondary formate binding site is observed in crystals soaked with substrate. Water molecules are excluded from the FDH catalytic site when the substrate is bound. The angle between the plane of the NAD+ cofactor pyridine ring and the plane of the formate molecule is around 27°. Additionally, structures of a FDH mutant enzyme, N120C, in complex with the reduced form of the cofactor have also been determined both in the presence and absence of formate bound at the secondary site. These structures provide further understanding of the catalytic mechanism of this fungal enzyme.

Serum kallistatin level is decreased in women with preeclampsia.

OBJECTIVES: To evaluate the serum levels of the serine proteinase inhibitor kallistatin in women with preeclampsia (PE). METHODS: The clinical and laboratory parameters of 55 consecutive women with early-onset PE (EOPE) and 55 consecutive women with late-onset PE (LOPE) were compared with 110 consecutive gestational age (GA)-matched (±1 week) pregnant women with an uncomplicated pregnancy and an appropriate for gestational age fetus. RESULTS: Mean serum kallistatin was significantly lower in women with PE compared to the GA-matched-controls (27.74±8.29 ng/mL vs. 37.86±20.64 ng/mL, p<0.001); in women with EOPE compared to that of women in the control group GA-matched for EOPE (24.85±6.65 ng/mL vs. 33.37±17.46 ng/mL, p=0.002); and in women with LOPE compared to that of women in the control group GA-matched for LOPE (30.87±8.81 ng/mL vs. 42.25±22.67 ng/mL, p=0.002). Mean serum kallistatin was significantly lower in women with EOPE compared to LOPE (24.85±6.65 ng/mL vs. 30.87±8.81 ng/mL, p<0.001). Serum kallistatin had negative correlations with systolic and diastolic blood pressure, creatinine, and positive correlation with GA at sampling and GA at birth. CONCLUSIONS: Serum kallistatin levels are decreased in preeclamptic pregnancies compared to the GA-matched-controls. This decrease was also significant in women with EOPE compared to LOPE. Serum kallistatin had negative correlation with systolic and diastolic blood pressure, creatinine and positive correlation with GA at sampling and GA at birth.

Angiotensin II type 2 receptor blocker PD123319 has more beneficial effects than losartan on ischemia-reperfusion injury and oxidative damage in isolated rat heart.

Our study aimed to determine the effects of losartan and PD123319 in ischemia-reperfusion (IR) injury in isolated perfused rat heart. The study used 40 male Wistar albino rats that were grouped as Control, IR, and IR treatment groups that received losartan (20 mg/kg), PD123319 (20 mg/kg), and losartan+PD123319. The hearts were attached to Langendorff isolated heart system by employing in situ cannulation method, and cardiodynamic parameters were recorded during the experiment. At the end of experiment, hearts were retained for biochemical analysis and all data were statistically evaluated. A partial recovery of cardiodynamic parameters was observed in all treatment groups. A significant increase in oxidative stress parameters were seen in the IR group, whereas all treatment groups exhibited lower increase. Furthermore, levels of all antioxidant parameters were significantly lower in the IR group, but higher in the treatment groups. Effects on all parameters were much more remarkable in the PD123319 group. Levels of angiotensin II and renin were increased (P < 0.001) with IR application and decreased (P < 0.001) with the treatment of both antagonists. In conclusion, treatment of losartan and PD123319 played a cardioprotective role against IR injury, PD123319 being more effective in this protection.

Three new circulating microRNAs may be associated with wet age-related macular degeneration.

This study investigates the circulating microRNA (miRNA) expression profiles in patients with age-related macular degeneration (AMD) and the role of miRNA in wet AMD and its pathways. Exosomes were extracted from serum samples of AMD patients (n = 70) and a control group (n = 50). After isolating miRNA from the exosomes, miRNAs were transformed into cDNA. In the control and AMD samples, the expression was compared with a panel including 175 genes using the PCR array method. Target genes and pathways of miRNAs were detected by KEGG and Biocarta signaling pathway enrichments. Comparing the serum samples between groups revealed that the expression levels of 15 microRNAs within 175 genes had significantly changed. In the validation studies, miR-129-3p and miR-132-3p had no significant expression in AMD group compared to the controls. miR-486-5p and miR-626 had higher expression in AMD patients compared to the control group, while miR-885-5p showed significantly lower expression. Pathway analysis revealed that these miRNAs may have critical roles in the apoptosis and neovascularization pathways. The data suggest that some miRNAs within the serum may have a role in the pathogenesis of wet AMD. Further studies are needed to examine the use of these miRNAs as biomarkers.

Can follicular Emmprin and BMP 4 levels predict ICSI outcome?

PURPOSE: To evaluate the relationship of clinical pregnancy rates with bone morphogenetic proteins 2-4-7 (BMP 2, 4, 7), growth differentiation factor 9 (GDF 9), and Emmprin levels in follicular fluid of intracytoplasmic sperm injection patients. METHODS: Follicular fluid of 77 patients who underwent ICSI procedure was collected during the oocyte retrieval procedure. And follicular fluid levels of BMP 2, BMP 4, BMP 7, GDF 9, and Emmprin (Basigin) were measured and compared for clinical pregnancy rates. RESULTS: Follicular levels of BMP 4 was significantly higher whereas Emmprin levels were lower in patients who had achieved clinically diagnosed pregnancy compared with those who did not achieve clinical pregnancy after ICSI procedure (P = 0.007 and P = 0.035, respectively). BMP 2, BMP 7, and GDF 9 levels were comparable for both groups. CONCLUSION: Clinical pregnancy rates after ICSI may be associated with follicular fluid levels of Emmprin and BMP 4. Follicular levels of Emmprin and BMP 4 can be used as a marker (as markers for predicting ICSI outcomes) for a better ICSI outcome.

Quantitative evaluation of dental anxiety indicators in the serum and saliva samples of children treated under general anesthesia.

OBJECTIVES: Dental anxiety level has been previously associated with oral health status. Since general anesthesia (GA) allows dental treatments to be performed in anxious children with a high number of caries, we aimed to evaluate the dental anxiety levels of these children before and after dental treatments performed under GA. MATERIALS AND METHODS: Thirty-eight children with high anxiety aged between 35 and 72 months who required multiple dental treatments to be performed under GA were included in the study. Frankl's Behavior Rating Scale, sitting patterns, Facial Image Scale, and Children's Fear Survey Schedule-Dental Subscale (completed by the children's parents) were recorded before and after the dental treatments performed under GA. Pre-treatment and post-treatment biochemical parameters, including cortisol, alpha-amylase, and chromogranin A levels, in saliva and serum samples were also evaluated. RESULTS: The psychometric scales showed a statistically significant reduction in the post-treatment dental anxiety levels of the children compared with the pre-treatment anxiety levels. Additionally, the biochemical parameters measured in the serum and whole saliva samples showed a decrease after treatments performed under GA. CONCLUSIONS: Our study results suggest that performing dental treatments under GA can reduce the dental anxiety levels of children with a high number of caries.

Relationship between hyperandrogenism, obesity, inflammation and polycystic ovary syndrome.

This prospective study aimed to determine the status of circulating levels of C-reactive protein (CRP), tumor necrosis factor α (TNF-α), IL-27, IL-35, IL-37, α-1 acid glycoprotein in patients with polycystic ovary syndrome (PCOS) compared with controls and to evaluate their relation with hyperandrogenism and obesity. Forty-eight patients with PCOS (29 obese, 19 lean) and 40 healthy controls (20 obese, 20 lean) were enrolled. CRP, TNF-α, IL-27, IL-35, IL-37, α-1 acid glycoprotein, sex hormone-binding globulin (SHBG), dehydroepiandrosterone sulfate (DHEA-S) levels were measured. Levels of total testosterone, A4, DHEA-S were significantly higher in patients with PCOS than in controls both in the obese and lean groups, while levels of SHBG were significantly lower in all patients with PCOS than in all (p < 0.05). Free androgen index (FAI) values were significantly higher in all patients with PCOS than in all controls (all p < 0.05). Levels of CRP, TNF-α, α-1 acid glycoprotein were significantly increased in all patients with PCOS compared with all controls (all p < 0.001). FAI had a positive correlation with CRP, TNF-α, α-1 acid glycoprotein, a negative correlation with IL-27, IL-25, IL-37 (all p < 0.01). Body mass index had a negative correlation with IL-27, IL-35, IL-37, a positive correlation with α-1 acid glycoprotein, FAI (p < 0.05). The findings confirm the proinflammatory state of PCOS. Moreover, obesity along with PCOS significantly elevates the inflammatory status and hyperandrogenism.

Pre and postnatal exposure to 900 MHz electromagnetic fields induce inflammation and oxidative stress, and alter renin-angiotensin system components differently in male and female offsprings.

AIMS: This study was designed to investigate inflammation, oxidative stress and renin-angiotensin system components in brain and kidney tissues of female and male rats prenatally and/or postnatally exposed to 900 MHz electromagnetic field (EMF). It is aimed to evaluate the biological effects of 900 MHz EMF exposure due to the increase in mobile phone use and especially the more widespread use of the GSM 900 system. MAIN METHODS: Male and female Wistar albino offsprings were divided into four groups of control, prenatal, postnatal, and prenatal+postnatal exposed to 900 MHz EMF for 1 h/day (23 days during pregnancy for prenatal period, 40 days for postnatal period). The brain and kidney tissues were collected when they reached puberty. KEY FINDINGS: It was found that the total oxidant status, IL-2, IL-6, and TNF-α levels increased (p < 0.001) and the total antioxidant status levels decreased (p < 0.001) in all three EMF groups comparing to controls in both male and female brain and kidney tissues. The renin- angiotensin system components such as angiotensinogen, renin, angiotensin type 1 and type 2 receptors, and MAS1-like G protein-coupled receptor expression were higher (p < 0.001) in all three EMF exposure groups comparing to controls in both male and female brain and kidney tissues. Although there are some differences of the levels of proinflammatory markers, ROS components and RAS components in brain and kidney tissues between males and females, the common result of all groups was increase in oxidative stress, inflammation markers and angiotensin system components with exposure to 900 MHz EMF. SIGNIFICANCE: In conclusion, our study suggested that the 900 MHz EMF can activate brain and kidney renin-angiotensin system, and this activation is maybe related to inflammation and oxidative stress in both male and female offsprings.

Structural analysis of wild-type and Val120Thr mutant Candida boidinii formate dehydrogenase by X-ray crystallography.

Candida boidinii NAD+-dependent formate dehydrogenase (CbFDH) has gained significant attention for its potential application in the production of biofuels and various industrial chemicals from inorganic carbon dioxide. The present study reports the atomic X-ray crystal structures of wild-type CbFDH at cryogenic and ambient temperatures, as well as that of the Val120Thr mutant at cryogenic temperature, determined at the Turkish Light Source `Turkish DeLight'. The structures reveal new hydrogen bonds between Thr120 and water molecules in the active site of the mutant CbFDH, suggesting increased stability of the active site and more efficient electron transfer during the reaction. Further experimental data is needed to test these hypotheses. Collectively, these findings provide invaluable insights into future protein-engineering efforts that could potentially enhance the efficiency and effectiveness of CbFDH.

Investigation of irisin's role in pubertal onset physiology in female rats.

OBJECTIVE: The timing of pubertal development is closely related to metabolic status and energy reserves. It is thought that irisin, which is involved in the regulation of energy metabolism and is shown to be present in the hypothalamo-pituitary-gonadal (HPG) axis, may play a role in this process. In our study, we aimed to investigate the effect of irisin administration on pubertal development and HPG axis in rats. DESIGN-METHODS: 36 female rats were included in the study were divided into 3 groups: 100 ng/kg/day irisin treatment group (irisin-100), 50 ng/kg/day irisin treatment group (irisin-50), and control group. On the 38th day, serum samples were taken to determine levels of luteinizing hormone (LH) and follicle stimulating hormone (FSH), estradiol and irisin. Brain hypothalamus samples were taken to determine levels of pulsatile gonadotropin-releasing hormone (GnRH), kisspeptin, neurokinin-B, dynorphin (Dyn), and makorin ring finger protein-3 (MKRN3). RESULTS: Vaginal opening and estrus were seen firstly in the irisin-100 group. At the end of the study, the highest rate of vaginal patency was found in the irisin-100 group. Hypothalamic protein expression levels of GnRH, NKB and Kiss1 in homogenates; serum FSH, LH, and estradiol levels were the highest in the irisin-100 group, followed by the irisin-50 and control groups, respectively. Ovarian sizes were significantly greater in the irisin-100 group compared to the other groups. The hypothalamic protein expression levels of MKRN3 and Dyn were the lowest in the irisin-100 group. CONCLUSIONS: In this experimental study, irisin triggered the onset of puberty in a dose-dependent manner. Irisin administration caused the excitatory system to dominate in the hypothalamic GnRH pulse generator.

Baseline serum vitamin A and vitamin C levels and their association with disease severity in COVID-19 patients.

AIM: We aimed to investigate the association between the serum concentrations of Vitamin A and Vitamin C and the severity of the COVID-19.  Methods: Fifty-three consecutive PCR (+) COVID-19 patients admitted to a dedicated ward were enrolled in this study. Blood samples for serum Vitamin A and C measurements were drawn from all participants upon admission. All subjects underwent thoracic CT imaging prior to hospitalization. CT severity score (CT-SS) was then calculated for determining the extent of pulmonary involvement. A group of healthy volunteers, in whom COVID-19 was ruled out, were assigned to the control group (n=26). These groups were compared by demographic features and serum vitamin A and C levels. The relationship between serum concentrations of these vitamins and pre-defined outcome measures, CT-SS and length of hospitalization (LOH), was also assessed.  Results: In COVID-19 patients, serum Vitamin A (ng/ml, 494±96 vs. 698±93; p<0.001) and Vitamin C (ng/ml, 2961 [1991-31718] vs. 3953 [1385-8779]; p=0.007) levels were significantly lower with respect to healthy controls. According to the results of correlation analyses, there was a significant negative association between Vitamin A level and outcome measures (LOH, r=-0.293; p=0.009 and CT-SS, r=-0.289; p=0.010). The negative correlations between Vitamin C level and those measures were even more prominent (LOH, r=-0.478; p<0.001 and CT-SS, r=-0.734: p<0.001). CONCLUSION: COVID-19 patients had lower baseline serum Vitamin A and Vitamin C levels as compared to healthy controls. In subjects with COVID-19, Vitamin A and Vitamin C levels were negatively correlated with CT-SS and LOH.