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.

Variants in TNF and NOS3 (eNOS) genes associated with sepsis in adult patients.

BACKGROUND: Sepsis is a life-threatening condition caused by a dysregulated host response to infections and is a leading cause of death in hospitalized patients. The present study aimed to elucidate the possible association between sepsis and the tumor necrosis factor (TNF) gene -308G/A (rs1800629) polymorphism, as well as endothelial nitric oxide synthase (eNOS, NOS3) gene -786T/C (rs2070744), 4a/4b (27 bp-VNTR in intron 4, rs61722009) and 894G/T (Glu298Asp, rs1799983) polymorphisms. METHODS: In total, 188 septic adult cases and 188 healthy controls were enrolled. Genomic DNAs from the controls and patients were analyzed by polymerase chain reaction and restriction fragment length polymorphism methods. RESULTS: There were significant associations between the G/G genotype and G allele of the TNF -308G/A (rs1800629) polymorphism in the sepsis group (p < 0.001). The presence of the T/C genotype (p = 0.002) and C allele (p = 0.001) of the -786T/C (rs2070744) was markedly associated with an increased risk of sepsis. However, no significant associations were found with 4a/4b (27 bp-VNTR in intron 4, rs61722009) and 894G/T (Glu298Asp, rs1799983) polymorphisms. Higher 4bGC and lower 4bTT haplotype frequencies were associated with sepsis. CONCLUSIONS: Our results strongly suggest that TNF gene (-308G/A, rs1800629) and NOS3 gene -786T/C (rs2070744) polymorphisms may modify individual susceptibility to sepsis in the Turkish population.

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 the association between Rho/Rho-kinase gene polymorphisms and systemic sclerosis.

Systemic sclerosis (SSc) is a disease characterized by inflammation, vascular abnormalities and fibrosis. The role of Rho/Rho-kinase pathway was demonstrated in the pathogenesis of fibrosis, inflammation and vascular abnormalities. This study was aimed to investigate the relation between SSc and Rho/Rho-kinase gene polymorphisms. The study included 339 patients with SSc and 302 healthy subjects who were apparently healthy and at similar age and gender. Genotype distributions and allele frequencies were detected by using Chi-square test or Fisher's exact Chi-square test between groups, and the haplotype analysis was applied using online program (SHEsis). Significant association was found in a polymorphism in the ROCK1 gene (rs35996865), a polymorphism in ROCK2 gene (rs10178332), a polymorphism in RhoA gene (rs2177268) and two polymorphisms in RhoC gene (rs11102522 and rs11538960) with SSc disease (p < 0.0022). In this study, association between SSc disease and Rho/Rho-kinase gene polymorphisms was investigated for the first time; significant associations between ROCK1, ROCK2, RhoA and RhoC gene polymorphisms and SSc disease were demonstrated. The results strongly suggest that this SNP may be an important risk factor for development of SSc. However, further validation of these findings in an independent cohort is necessary.

Investigation of intercellular adhesion molecules (ICAMs) gene expressions in patients with Barrett's esophagus.

The adhesion molecules play a major role in inflammation as well as in neoplastic diseases. The aim of this study is to evaluate the expressions of the adhesion molecules, intercellular adhesion molecule 1 (ICAM-1), ICAM-2, and ICAM-3, in Barrett's esophagus, recognized as a premalign lesion for esophageal cancer and related to inflammation. Eighteen patients with Barrett's esophagus according to endoscopy and 25 volunteers without Barrett's esophagus disease were included in the study. Tissue samples were supplied by biopsy and used for both gene expression and immunohistochemical analysis. The significance of the differences between the two groups was assessed by Student's t test. The ICAM-1 expression level was fivefold higher in the patient group compared with that of the control. There was an increase in the serum level of ICAM-1 in patients compared to that of the controls, but this increase was not significant. ICAM-2 levels were also increased in the patient group, but it was not significant. There was no difference between controls and patients in ICAM-3 levels. Significantly higher levels of ICAM-1 gene expression make us think that ICAM-1 may play an important role in Barrett's esophagus. We think that more studies, with larger patient groups and preferably detailed histopathological and clinical evaluations, are needed to explain the severity of ICAM-1, ICAM-2, and ICAM-3 molecules in Barrett's esophagus.

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.

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.

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.

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.

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.

Evaluation of the Rho-kinase gene expression and polymorphisms in adult patients with acute appendicitis: a differential impact of gender.

OBJECTIVE: Acute appendicitis represents one of the most common causes of acute intra-abdominal emergencies worldwide. In this case-control study, we aimed to investigate associations of Rho-kinase gene expression and polymorphisms with acute appendicitis in a Turkish population. We also aimed to study the effects of gender on these parameters. METHODS: A total of 93 unrelated patients with acute appendicitis and 93 healthy controls in the Department of Emergency Medicine, Erciyes University, between June 2019 and June 2021 were included in this study. Genomic DNA was isolated from peripheral leukocytes, and the LightCycler 480 II real-time polymerase chain reaction was utilized to detect Rho-kinase1 gene rs35996865 and Rho-kinase2 gene rs2230774 (Thr431Asn) polymorphisms. Quantitative real-time polymerase chain reaction was applied to determine Rho-kinase1 and Rho-kinase2 gene expressions. RESULTS: There was a marked increase in Rho-kinase1, but not in Rho-kinase2, mRNA expression, and this increase was evident only in male patients (p=0.0008). No significant differences were found in allele and genotype frequencies for Rho-kinase1 gene rs35996865 and Rho-kinase2 gene rs2230774 polymorphisms between the patients with acute appendicitis and the control group. CONCLUSIONS: Our data imply that Rho-kinase1 (rs35996865) and Rho-kinase2 (rs2230774) gene variants are not risk factors for the development of acute appendicitis in the Turkish population. However, increased mRNA expression of the Rho-kinase1 gene in males indicated that Rho-kinase1 is involved in the pathogenesis of acute appendicitis in a gender-specific way.

Evaluation of the rs35996865 polymorphism of the ROCK1 gene in sepsis.

OBJECTIVE: Sepsis is a complex and serious medical condition resulting from the activation of an innate host response to infections. The etiology of sepsis is complex and can be influenced by genetic susceptibility. The purpose of the present study was to investigate a possible association of Rho-kinase 1 (ROCK1) gene polymorphism with sepsis in a Turkish population. METHODS: The study group consisted of 100 unrelated patients with sepsis and 100 healthy controls. Genomic DNA was isolated from peripheral leukocytes from EDTA-containing blood using the QIAamp DNA Blood Mini Kit. ROCK1 gene rs35996865 and rs112130712 (Lys1054Arg) polymorphisms were analyzed in genomic DNA using the LightCycler 480 II real-time polymerase chain reaction. RESULTS: There were no significant differences in allele and genotype frequencies for ROCK1 gene rs35996865 polymorphism between the patients with sepsis and control group (p>0.05). Additionally, no association was detected between the rs35996865 polymorphism and mortality in the patient group. No polymorphism was detected with ROCK1 gene rs112130712 (Lys1054Arg) in our study groups. CONCLUSIONS: Our data showed that there is no marked association between the rs35996865 polymorphism and sepsis. Therefore, these results suggest that ROCK1 gene rs35996865 polymorphism is not risk factor for the development of sepsis in the Turkish population.

Investigation of Dynamic Thiol/Disulfide Homeostasis and Nitrosative Stress in Patients with Wilson Disease.

BACKGROUND: Wilson disease (WD) is an autosomal recessive inherited disorder of copper (Cu2+) metabolism, resulting in Cu2+ accumulation and liver and central nervous system toxicity. Oxidative stress may have a role in the pathogenesis of Wilson disease, but the roles of thiol/disulfide homeostasis and nitrosative stress have not been examined. The purpose of this study was to evaluate whether there is a modification in thiol/disulfide homeostasis and nitrosative stress in patients with Wilson disease. METHODS: A total of 50 patients with Wilson disease (42 under drug treatment and 8 newly diagnosed patients with no drug treatment) and 50 healthy gender- and age-matched controls were enrolled for this study. Serum native thiol and total thiol levels were measured with a spectrophotometric method. The number of disulfide bonds and the related ratios were determined from these measurements. Serum nitric oxide (NO) and 3-nitrotyrosine (3-NT) levels were analyzed using chemiluminescence and ELISA assays, respectively. RESULTS: The average native thiol levels of the patient group under drug treatment were found to be markedly higher than the levels of controls (P < .05). We detected no marked changes in total thiol and disulfide levels, and disulfide/total thiol, disulfide/native thiol, or native thiol/total thiol ratios between groups. We found significant elevations in NO levels in Wilson disease group before drug treatment, and the 3-NT levels in the Wilson disease groups prior to (P < .05) and under drug treatment (P < .01), when compared to controls. CONCLUSION: Our data are the first to show that nitrosative stress and thiol/disulfide homeostasis can contribute to the pathogenesis of Wilson disease.

CDC 25A gene 263C/T, -350C/T, and -51C/G polymorphisms in breast carcinoma.

The family of cell division cycle 25 (CDC25) phosphatase is one of the important regulators of the cell cycle progression. In mammalian cells, three isoforms have been identified: CDC25A, CDC25B, and CDC25C. CDC25A is required to enter S time, and the overexpression of this phosphatase accelerates the entrance to S time. CDC25A overexpression could render tumor cells less sensitive to DNA replication checkpoints, thereby contributing to their genomic instability. We aimed to investigate, for the first time, the frequency of human CDC25A gene SNPs in metastatic and non-metastatic breast cancer. Total number of 281 eligible patients with histologically confirmed incident of breast cancer and 137 cancer-free controls were included. The detection of CDC25A gene polymorphisms was achieved with real-time polymerase chain reaction and restriction fragment length polymorphism techniques. We found that the 263C/T polymorphism was significantly associated with breast cancer and risk of metastasis. The -350C/T polymorphism in the promoter region of CDC25A gene was found to associate with neither breast cancer nor metastasis. The other promoter polymorphism -51C/G in the CDC25A gene associated with breast cancer but not associated with metastasis. These data suggest that 263C/T and -51C/G polymorphisms of CDC25A gene could be candidate markers for earlier diagnosis and targets for breast cancer therapy.

Lack of association between urotensin-II (UTS2) gene polymorphisms (Thr21Met and Ser89Asn) and migraine.

Migraine is a common neurovascular brain disorder with heterogeneous clinical presentation, including recurrent headache attacks. The pathophysiology of migraine is complex, and a number of genomic regions have been associated with the development of migraine. In this study, we analyzed the allele and genotype frequencies of the urotensin-II gene (UTS2) polymorphisms, Thr21Met and Ser89Asn, among Turkish patients with migraine. A total of 146 patients with migraine (14 with aura [MA group] and 132 without aura [MO group]) were genotyped for Thr21Met and Ser89Asn polymorphisms and compared with 154 age- and sex-matched healthy controls. The UTS2 gene polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). No significant differences were observed in allele and genotype frequencies for Thr21Met and Ser89Asn polymorphisms between the patients with migraine and control group. Similarly, we did not observe significant differences in allele and genotype frequencies between MA and MO and control group. Moreover, the haplotype analysis showed no association between UTS2 gene haplotypes (MN, MS, TN, and TS) and migraine. In summary, Thr21Met and Ser89Asn polymorphisms of the UTS2 gene are not risk factors for migraine in our sample of Turkish migraine patients.

Prevalence and characteristics of coronary artery anomalies in children with congenital heart disease diagnosed with coronary angiography.

OBJECTIVE: Aim of the present study was to determine the prevalence of coronary artery anomalies in children with congenital heart disease. METHODS: Data of 1138 consecutive patients who were referred for cardiac catheterization and angiography for assessment of coronary anomaly between January 2005 and December 2009 were retrospectively analyzed. Total of 515 patients whose coronary arteries could be examined through left ventricle and aortic root injection were included in the study. RESULTS: Of 515 angiograms with visible coronaries, 42 patients (20 males, 22 females; mean age: 5.3±2.0 years) were found to have final diagnosis of coronary anomaly. Prevalence of coronary artery anomalies was 8.16% in this study. It was determined that 38 (90.4%) were anomalies of origination, 2 (4.8%) were anomalies of intrinsic coronary arterial anatomy, and 2 (4.8%) were anomalies of coronary termination. Most common coronary artery abnormality was anomalous origin of the right coronary artery from the left aortic sinus (16 patients; 38.1%), and the most common congenital heart disease was tetralogy of Fallot (18 patients; 42.9%). CONCLUSION: Recognizing variability of coronary artery anomalies is critical when considering surgical or interventional therapies in children with congenital heart disease.

Evaluation of the rs35996865 polymorphism of the ROCK1 gene in sepsis

SUMMARY OBJECTIVE: Sepsis is a complex and serious medical condition resulting from the activation of an innate host response to infections. The etiology of sepsis is complex and can be influenced by genetic susceptibility. The purpose of the present study was to investigate a possible association of Rho-kinase 1 (ROCK1) gene polymorphism with sepsis in a Turkish population. METHODS: The study group consisted of 100 unrelated patients with sepsis and 100 healthy controls. Genomic DNA was isolated from peripheral leukocytes from EDTA-containing blood using the QIAamp DNA Blood Mini Kit. ROCK1 gene rs35996865 and rs112130712 (Lys1054Arg) polymorphisms were analyzed in genomic DNA using the LightCycler 480 II real-time polymerase chain reaction. RESULTS: There were no significant differences in allele and genotype frequencies for ROCK1 gene rs35996865 polymorphism between the patients with sepsis and control group (p>0.05). Additionally, no association was detected between the rs35996865 polymorphism and mortality in the patient group. No polymorphism was detected with ROCK1 gene rs112130712 (Lys1054Arg) in our study groups. CONCLUSIONS: Our data showed that there is no marked association between the rs35996865 polymorphism and sepsis. Therefore, these results suggest that ROCK1 gene rs35996865 polymorphism is not risk factor for the development of sepsis in the Turkish population.

Evaluation of the Rho-kinase gene expression and polymorphisms in adult patients with acute appendicitis: a differential impact of gender

SUMMARY OBJECTIVE: Acute appendicitis represents one of the most common causes of acute intra-abdominal emergencies worldwide. In this case-control study, we aimed to investigate associations of Rho-kinase gene expression and polymorphisms with acute appendicitis in a Turkish population. We also aimed to study the effects of gender on these parameters. METHODS: A total of 93 unrelated patients with acute appendicitis and 93 healthy controls in the Department of Emergency Medicine, Erciyes University, between June 2019 and June 2021 were included in this study. Genomic DNA was isolated from peripheral leukocytes, and the LightCycler 480 II real-time polymerase chain reaction was utilized to detect Rho-kinase1 gene rs35996865 and Rho-kinase2 gene rs2230774 (Thr431Asn) polymorphisms. Quantitative real-time polymerase chain reaction was applied to determine Rho-kinase1 and Rho-kinase2 gene expressions. RESULTS: There was a marked increase in Rho-kinase1, but not in Rho-kinase2, mRNA expression, and this increase was evident only in male patients (p=0.0008). No significant differences were found in allele and genotype frequencies for Rho-kinase1 gene rs35996865 and Rho-kinase2 gene rs2230774 polymorphisms between the patients with acute appendicitis and the control group. CONCLUSIONS: Our data imply that Rho-kinase1 (rs35996865) and Rho-kinase2 (rs2230774) gene variants are not risk factors for the development of acute appendicitis in the Turkish population. However, increased mRNA expression of the Rho-kinase1 gene in males indicated that Rho-kinase1 is involved in the pathogenesis of acute appendicitis in a gender-specific way.

Polymorphism of CYP3A4 and ABCB1 genes increase the risk of neuropathy in breast cancer patients treated with paclitaxel and docetaxel.

BACKGROUND: Interindividual variability of pharmacogenetics may account for unpredictable neurotoxicities of taxanes. METHODS: From March 2011 to June 2015, female patients with operable breast cancer who had received docetaxel- or paclitaxel-containing adjuvant chemotherapy were included in this study. All patients were treated with single-agent paclitaxel intravenously (IV) 175 mg/m(2) every 3 weeks for four cycles, or IV 80 mg/m(2) weekly for 12 cycles, and IV 100 mg/m(2) docetaxel for four cycles as adjuvant treatment. We evaluated the relationship between neurotoxicity of taxanes and single-nucleotide polymorphisms of ABCB1, CYP3A4, ERCC1, ERCC2, FGFR4, TP53, ERBB2, and CYP2C8 genes. Taxane-induced neurotoxicity during the treatment was evaluated according to the National Cancer Institute Common Toxicity Criteria version 4.03 prior to each cycle. Chi-squared tests were used to compare the two groups, and multivariate binary logistic regression models were used for determining possible risk factors of neuropathy. RESULTS: Pharmacogenetic analysis was performed in 219 females. ABCB1 3435 TT genotype had significantly higher risk for grade ≥2 neurotoxicity (odds ratio [OR]: 2.759, 95% confidence interval [CI]: 1.172-6.493, P: 0.017) compared to TC and CC genotype, and also CYP3A4 392 AA and AG genotype had significantly higher risk for grade ≥2 neurotoxicity (OR: 2.259, 95% CI: 1.033-4.941, P: 0.038) compared to GG genotype. For FDGF4 gene with AG and GG genotype, OR was 1.879 (95% CI: 1.001-3.525, P: 0.048) compared to AA genotype with regard to any grade of neuropathy risk. We could not find any other association of other genotypes with neurotoxicity grades. CONCLUSION: ABCB1 3435 TT genotype and CYP3A4 392 AA/AG genotypes may be used as predictors of neurotoxicity during taxane chemotherapy.