An update on approved and emerging drugs for the treatment of postpartum depression.

Depression, anxiety and psychotic disorders are common perinatal mental health disorders in the postpartum period. Depressive symptoms that occur postpartum are also present in the prenatal period in 50% of patients. Risk factors for the development of postpartum depression include poor relationship with the partner, lack of social support, mother’s low socioeconomic status and multiparity. It has been determined that reproductive hormones change significantly during peripartum. Progesterone is one of these hormones and acts on the central nervous system starting from the fetal period; neurogenesis, neuromodulation, sedation are some of these effects. It has also been observed that progesterone has positive effects on learning, memory and mood. Progesterone exerts its effects on the central nervous system by converting into its metabolite allopregnanolone. Allopregnanolone is one of the neuroactive steroids, and found in similar amounts in the circulation of pregnant women and fetuses. It acts on synaptic and extrasynaptic γ-aminobutyric acid type A (GABAA) receptors and is a positive allosteric modulator of the GABAA receptor. Allopregnanolone increases both the receptor’s opening frequency and its open duration and improves GABAergic current. Low serum allopregnanolone levels in the second trimester are predictive of postpartum depression. Each 1 ng/mL increase in serum allopregnanolone level reduces the risk of development of postpartum depression by 63%. Brexanolone and zuranolone are synthetic allopregnanolone preparations approved by the FDA for use in female patients with postpartum depression. They act via positive allosteric modulation on the GABAA receptor. Brexanolone is administered via intravenous infusion at varying infusion rates in a healthcare facility over 60 hours. Its effect starts immediately after treatment and continues until the 30th day of follow-up, and depressive mood does not recur. Zuranolone was developed for oral use, and administered as a single dose of 50 mg after a fatty meal. Their effectiveness has been demonstrated in patients with treatment-resistant depression. The development of other novel agents that act on the GABAA receptor and other pathways for the treatment of postpartum depression is in progress.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Assessment of the effect of laser irradiations at different wavelengths (660, 810, 980, and 1064 nm) on autophagy in a rat model of mucositis.

It is known that high-dose radiation has an effect on tissue healing, but tissue healing does not occur when low dose radiation is applied. To clarify this issue, we compare the treatment success of low dose radiation with programmed cell death mechanisms on wounded tissue. In this study, we aimed to investigate the interactions of low and high-dose radiation using an autophagic mechanism. We included 35 adult Wistar-Albino rats in this study. All animals were injected with 100 mg/kg of 5-fluorouracil (5-FU) on the first day and 65 mg/kg of 5-FU on the third day. The tips of 18-gauge needles were used to develop a superficial scratching on the left cheek pouch mucosa by dragging in a linear movement on third and fifth days. After mucositis formation was clinically detected, animals were divided into five groups (n = 7). Different wavelengths of laser irradiations (1064 nm, Fidelis Plus, Fotona, Slovenia; 980 nm, FOX laser, A.R.C., Germany; 810 nm, Fotona XD, Fotona, Slovenia; 660 nm, HELBO, Medizintechnik GmbH, Wels, Austria) were performed on four groups once daily for 4 days. The laser irradiation was not performed on the control group. To get the tissue from the left cheek at the end of fourth day from all animals, oval excisional biopsy was performed. Molecular analysis assessments of pathological and normal tissue taken were performed. For this purpose, the expression analysis of autophagy genes was performed. The results were evaluated by normalization and statistics analysis. We found that Ulk1, Beclin1, and Atg5 expression levels were increased in the rats when the Nd:YAG laser was applied. This increase showed that a 1064-nm laser is needed to activate the autophagic mechanism. However, in the diode applications, we found that Beclin1, Atg10, Atg5, and Atg7 expressions numerically decreased. Atg5 is responsible for the elongation of autophagosome. Becn1 is a control gene in the control mechanism of autophagy. The reduction of the expression of these genes leads us to think that it may depend on the effect of drug (5-FU) used to form model. Expressions of therapeutic genes increase to ensure hemostasis, but in our study, expressions were found to decrease. More detailed studies are needed.

Occurrence of Hashimoto's thyroiditis among the patients with Sydenham's chorea.

AIM: The purpose of this study was to examine the possible association of Hashimoto's thyroiditis (HT) with Sydenham's chorea (SC). MATERIALS AND METHODS: A total of 25 SC patients and 25 patients with the diagnosis of HT were included in the study. Neurological, cardiac, radiological abnormalities, clinical findings, and biochemical analysis were evaluated. RESULTS: Heart murmur as a result of mitral valve deformation was present in all SC group patients. No neurologic and cardiac abnormalities were noted in HT group. Serum thyroid-stimulating hormone (TSH), anti-thyroid peroxidase, and anti-thyroglobulin levels were found to be high in 4 patients of the SC group and called as SC with HT group. Significant elevation of serum TSH levels in SC with HT group (31.75 ± 3.71 µU/ml) was observed when compared to HT group (12.60 ± 4.24 µU/ml, p < 0.05). CONCLUSION: These results showed that HT can be occurred among the patients with SC with cardiac involvement.

Evaluation of TRPM (transient receptor potential melastatin) genes expressions in myocardial ischemia and reperfusion.

In the present study, the expression levels of TRPM1, TRPM2, TRPM3, TRPM4, TRPM5, TRPM6, TRPM7, and TRPM8 genes were evaluated in heart tissues after ischemia/reperfusion (IR). For this study, 30 albino male Wistar rats were equally divided into three groups as follows: Group 1: control group (n:10), Group II: ischemia group (ischemia for 60 min) (n:10) and Group III: IR (reperfusion 48 h after ischemia for 60 min and reperfusion for 48 h). The expression levels of the TRPM genes were analyzed by semi-quantitative reverse transcriptase-PCR. When compared to the ischemia control, the expression levels of TRPM2, TRPM4, and TRPM6 did not change, whereas that of TRPM7 increased. However, TRPM1, TRPM3, TRPM5, and TRPM8 were not expressed in heart tissue. Histopathological analysis of the myocardial tissues showed that the structures that were most damaged were those exposed to IR. The findings showed that there is a positive relationship between TRPM7 expression and myocardial IR injury.

Investigation of the Rho-kinase 2 gene Thr431Asn polymorphism in migraine.

BACKGROUND: Migraine has a complex etiology determined by genetic and environmental factors, but the molecular mechanisms and genetics of this disease have not yet been fully clarified. AIM: This case/control study was designed to analyze the genotype distributions and allele frequencies for the Rho-kinase 2 (ROCK2) gene Thr431Asn polymorphism among the migraine patients. MATERIALS AND METHODS: A total of 155 migraine patients and 155 healthy age and sex matched controls were included in this study. Genomic deoxyribonucleic acid from migraine patients and controls was analyzed by real-time polymerase chain reaction. RESULTS: Neither genotype distributions nor the allele frequencies for the Thr431Asn polymorphism showed a significant difference between the groups. In addition, there were no marked differences in genotype and allele frequencies for the migraine without aura and migraine with aura subgroups when compared with control group. CONCLUSION: This is the first study to show that the ROCK2 gene Thr431Asn polymorphism is not a risk factor for the migraine in the Turkish population.

Recent Progress and Perspectives in Sodium-Glucose Co-transporter 1/2 Inhibitors.

Sodium-Glucose Co-transporter-1/2 (SGLT1/2) inhibitors (also called glifozins) are a class of glucose-decreasing drugs in adults with Type 2 Diabetes (T2D). SGLT2 inhibitors diminish sodium and glucose reabsorption in the renal proximal convoluted tubule. Recent clinical trials have revealed that SGLT2 inhibitors might be beneficial for treating diseases other than diabetes, including chronic renal disease and Heart Failure (HF). Currently, SGLT2 inhibitors are recommended not only for the glycemic management of T2D but also for cardiovascular protection. SGLT2 inhibitors have become one of the foundational drugs for HF with reduced Ejection Fraction (HFrEF) treatment and the first medications with proven prognostic benefit in HF with preserved Ejection Fraction (HFpEF). At present, 11 SGLT1/2 inhibitors have been approved for clinical use in different countries. Beyond their anti-hyperglycemic effect, these inhibitors have shown clear cardio- and nephroprotective properties. A growing body of research studies suggests that SGLT1/2 inhibitors may provide potential clinical benefits in metabolic as well as oncological, hematological, and neurological disorders.

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

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

Effects of empagliflozin and dapagliflozin on serum humanin, MOTS-c levels, nitrosative stress, and ferroptosis parameters in diabetic patients with heart failure.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors produce cardioprotective effects on heart failure (HF), even in the absence of diabetes. However, the underlying mechanisms of this cardioprotective effect remain unexplored. The purpose of this study was to examine the effects of SGLT2 inhibitors on serum MOTS-c, humanin levels, nitrosative stress, and ferroptosis parameters in diabetic patients with HF with reduced ejection fraction (HFrEF). A total of 74 adult diabetic patients with HFrEF and 37 healthy controls were included in this prospective study. Half of the patients were using SGLT2 inhibitors (empagliflozin or dapagliflozin) for at least two months. Serum nitric oxide and 3-nitrotyrosine levels were markedly higher in diabetic patients with HFrEF than the control (P < 0.001), but these elevations were inhibited with SGLT2 inhibitors. Although SGLT2 inhibitors had no marked effect on humanin levels, they significantly augmented MOTS-c levels when compared to the control. SGLT2 inhibitors augmented GPX4 but inhibited ACSL4 levels when compared to diabetic patients with HF. However, TFRC levels were increased in the patient group (P < 0.001 for all) but not modified with SGLT2 inhibitors. Our results suggest that increased nitrosative stress is significantly depressed by SGLT2 inhibitors. This study was the first to show that SGLT2 inhibitors can stimulate MOTS-c, but not humanin, in diabetic patients with HFrEF. SGLT2 inhibitors reduced ferroptosis through elevation of GPX4 and suppression of ACSL4 levels. Our data suggest that SGLT2 inhibitors could produce cardioprotective effects through relieving ferroptosis, inhibiting nitosative stress, and stimulating mitochondrial MOTS-c release.

Association transient receptor potential melastatin channel gene polymorphism with primary open angle glaucoma.

PURPOSE: Genetic factors are shown to have a role in the development of primary open angle glaucoma (POAG). The aim of this study was to determine the effects of genetic polymorphisms of transient receptor potential melastatin (TRPM) channel genes on the risk of POAG in a Turkish population. METHODS: Genomic DNA was extracted from the leukocytes of the peripheral blood, and 26 single nucleotide polymorphisms in the TRPM channel genes were analyzed in 179 patients with POAG and in 182 healthy controls of similar age by using the BioMark HD dynamic array system. RESULTS: There were marked changes in the genotype (TT, 26.8%; CT, 66.7%; CC, 6.5%) and allele (T, 60.1%; C, 39.9%) frequencies for the TRPM5 gene rs34551253 (Ala456Thr, in exon 9) polymorphism in patients when compared to the controls (TT, 11.3%; CT, 74.6%; CC, 14.1%, p = 0.0009; T, 48.6%; A, 51.4%, p = 0.0063). However, no associations with the other 25 polymorphisms studied were found. CONCLUSIONS: This is the first study to examine the involvement of TRPM channel gene variations in the risk of incident POAG. This study demonstrated that the TRPM5 gene rs34551253 (Ala456Thr) polymorphism may be associated with increased risk of developing POAG in the Turkish population.

Investigation of the esophageal Rho-kinase expression in patients with Barrett's esophagus.

The mechanisms responsible for the malignant transformation in Barrett's esophagus (BE) are still poorly understood. The authors have evaluated the role of Rho-kinase (ROCK1 and ROCK2) expressions in patients with BE. All patients underwent upper gastrointestinal system endoscopy, which was confirmed histologically. Real-time PCR revealed no marked change in gene expressions of ROCK1 and ROCK2 at mRNA levels in BE when compared to controls. Immunohistochemical and western blot analyses showed no change in ROCK1 and ROCK2 protein expressions in BE. This study demonstrates that Rho-kinase gene and protein expressions are not modified in BE.

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

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

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

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

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

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