Effect of melatonin on low and high dose radiotherapy induced thyroid injury.

We investigated the radioprotective effect of melatonin (MEL) against thyroid gland damage in rats caused by flattening filter (FF) and flattening filter free (FFF) single dose X-ray beams. We used 48 female rats divided into six groups of eight: group 1, untreated control group; group 2, MEL treated group; group 3, FF-low dose rate radiotherapy (FF-LDR) group; group 4, FF-LDR + MEL group; group 5, FFF-high dose rate radiotherapy (FFF-HDR) group; group 6, FFF-HDR + MEL group. Groups 2, 4 and 6 rats were injected intraperitoneally (i.p.) with 10 mg/kg MEL 15 min before exposure to radiation. The head and neck regions of each rat in groups 3 and 5 and groups 4 and 6 were irradiated with 16 Gy at 6 MV X-ray in FF and FFF beam modes. The histopathology of the thyroid gland and salient biochemical parameters were assessed in all rats 10 days after radiotherapy. We found increased inflammation, vacuolization, degradation, swelling and necrosis, and M30 apoptosis and M65 necrosis indicators in groups 3 and 5 compared to group 1; however, we found significant reductions in histopathological and biochemical parameters following application of MEL. MEL treatment before FF-LDR and FFF-HDR radiotherapy minimized thyroid gland injury due to irradiation.

Effects of metformin, letrozole and atorvastatin on inflammation and apoptosis in experimental peritoneal and ovarian endometriosis in the rat.

Endometriosis is a common gynecological hurting disorder in which tissue is similar to the tissue that normally lines the inner layer of the uterus. It often causes fertility problems. Unfortunately, effective treatments are limited. Therefore it's important to explore an imperative and easily accessible treatment to alleviate the probable pathologies and preserve fertility in endometriosis. Consequently, we aimed to investigate the effects of metformin, letrozole, and atorvastatin on inflammation and apoptosis in experimentally induced ovarian and peritoneal endometriosis in rat models. In the present study, 35 rats were randomly divided into five groups. Group 1: sham-operated control group. Group 2: untreated endometriosis group. Group 3: given 100 mg/kg/day of oral metformin. Group 4: given 0.1 mg/kg/day of oral letrozole. Group 5: given 2.5 mg/kg/day of oral atorvastatin. At the end of the 28 days, we examined Ki67, Bax and Bcl-2 immunoexpressions in ovarian and peritoneal tissues, and IL-6, IL-8, and TNF-α levels were evaluated from the peritoneal fluid. All medical treatment groups showed a significant decrease in Ki67 expression. A significant increase in Bax expression was also observed in all samples from all medical treatment groups (other than the untreated endometriosis groups). Further, a significant decrease in Bcl-2 expression was found in all medical treatment groups. IL-6, IL-8, and TNF-α levels were significantly lower in all medical treatment groups than in the endometriosis groups. In conclusion; Metformin, letrozole, and atorvastatin showed apoptosis induction and anti-inflammatory effects on both ovarian and peritoneal endometriosis in experimental models.

Transcriptomic analysis of asymptomatic and symptomatic severe Turkish patients in SARS-CoV-2 infection.

Objective: Coronavirus disease 2019 (COVID-19), leading to mild infection (MI), acute respiratory distress syndrome or death in different persons. Although the basis of these variabilities has not been fully elucidated, some possible findings have been encountered. In the present study, we aimed to reveal genes with different expression profiles by next-generation sequencing of RNA isolated from blood taken from infected patients to reveal molecular causes of different response. Methods: Two healthy, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-negative control individuals (NCI), two SARS-CoV-2-positive patients who have MI, and two patients who have critical infection (CI) were included in the study. Total RNA was extracted from blood samples and sequenced. Raw RNA-Seq data were analyzed on Galaxy platform for the identification of differentially expressed genes and their pathway involvements. Results: We found that 199 and 521 genes were downregulated in whole blood of COVID-19-positive CI patients compared to NCI and MI patients, respectively. We identified 21 gene ontology pathways commonly downregulated in CI patients compared to both NCI and MI, mostly associated with innate and adaptive immune responses. Three hundred and fifty-four and 600 genes were found to be upregulated compared to NCI and MI, respectively. Upregulated six pathways included genes that function in inflammatory response and inflammatory cytokine release. Conclusion: The transcriptional profile of CI patients deviates more significantly from that of MI in terms of the number of differentially expressed genes, implying that genotypic differences may account for the severity of SARS-CoV-2 infection and inflammatory responses through differential regulation of gene expression. Therefore, further studies that involve whole genome analysis coupled with differential expression analysis are required in order to determine the dynamics of genotype - gene expression profile associations.

Comparison of MED 12 gene mutation and microRNA-124 expression in leiomyoma and myometrium of Turkish patients.

OBJECTIVES: It is believed that there are still unclear areas in the formation mechanism of leiomyomas. In our study, it was aimed to investigate the formation mechanisms of leiomyomas due to local MED 12 gene exon 2 mutation and local microRNA-124 expression in a Turkish population. MATERIAL AND METHODS: Thirty patients who underwent hysterectomy for leiomyoma uteri at Gaziantep University between January 2013 and January 2016 were included in our study. In the pathology specimens of these patients, the patient's myometrium tissue and her own leiomyoma tissue were analysed via quantitative Realtime PCR in association with MED 12 exon 2 mutation and microRNA-124 expression. RESULTS: The average age of the 30 patients included in our study is 46.67 ± 5.42 and 13 patients had single leiomyoma; 17 patients had more than one leiomyoma. There were significantly higher c.130G> T (p.G44C) mutation and c.131G> A (p.G44A) mutation of MED 12 gene exon in leiomyoma tissues than healthy myometrium tissues of same patients. There was a 3.7-fold decrease in the expression of microRNA-124 in leiomyoma tissues compared to intact eutopic myometrium tissues, but this difference was not statistically significant. CONCLUSIONS: In recent studies, it has been suggested that MED 12 gene may play an active role in the formation of fibroids. MED12 and ß-catenin / Wnt pathway were emphasized, and alternative genetic pathways are sought in fibroid formation. Also, tumour suppressor and oncogenesis effects of microRNAs have been demonstrated in many different studies. Since it is involved in the Wnt pathway, microRNA-124 has been blamed by some previous studies for the formation of fibroids. This study demonstrates that MED12 exon 2 mutations and probably microRNA-124 gene expressions might contribute to uterine leiomyoma pathology.

Histological and biochemical apoptosis changes of female rats' ovary by Zinc oxide nanoparticles and potential protective effects of l-arginine: An experimental study.

BACKGROUND: This research aims to investigate the adverse effects of ZnO NP on ovarian tissue and the follicular and menstrual cycle and the protective effects of l-arginine on the aforementioned tissues. MATERIAL AND METHODS: 30 rats were divided into five groups. The first group was the control group. The second and fourth groups received 100 mg/kg and 200 mg/kg ZnO NP, respectively. The third and fifth groups received the same doses of ZnO NP as the second and fourth groups, respectively. However, the third and fifth groups received an additional dose of 1.3 gr/kg of LA amino acid. ZnO NP and LA are given intraperitoneal for 21 days. Blood samples from each rat and a part of the ovarium were collected to test for gene expression and histological analysis. RESULTS: Compared to levels of housekeeping gene ß-actine, levels of apoptosis effectors such as Bax, Bcl, Caspase 3, and Caspase 9 were significantly increased in all groups. In groups that received doses of LA (three and five), atretic follicle size was smaller compared to groups that did not receive LA (two and four). In addition, in the third group, the secondary and primordial follicle's generated oocytes were smaller compared with groups two, four, and five. Compared with the control group, all groups experienced morphological degeneration of follicles and tissue. CONCLUSION: ZnO NP has inevitable, morphological, and physiological effects on the ovary and can detrimentally impact the tissue. LA can aid in the regeneration of the tissue and block damage induced by stress and toxicity.

Sarcopenia is associated with increased severe postoperative complications after colon cancer surgery.

INTRODUCTION: Studies have shown that sarcopenia is associated with poor outcomes in patients with gastrointestinal cancer undergoing surgery. We aimed to investigate the relationship between postoperative complications of sarcopenic patients who had been operated on for colon cancer and the effects on short-term mortality. MATERIAL AND METHODS: In this study, patients who had undergone colon cancer surgery between January 2013 and December 2018 were collected retrospectively. Sarcopenia was diagnosed by the skeletal muscle index (SMI) derived from a preoperative computed tomography scan. Multiple logistic regression analysis was performed to determine whether sarcopenia is associated with postoperative major complications (POMC). RESULTS: The study included 160 patients with a mean age of 62.4 ±12.6 years. Clavien-Dindo grade 1-2 (minor) complications were not significantly different between the groups (p = 0.896). However, grade ≥ 3 (major) complications were detected in 13 (17.8%) patients in the sarcopenic group (SG) and in 5 patients in the non-sarcopenic group (NSG) (5.7%) (p = 0.016). Length of intensive care unit (ICU) stay was longer in SG (p = 0.002) and there was no difference between 1-month and 6-month mortality rates (p = 0.273 and p = 0.402, respectively). According to univariate analyses, sarcopenia and age over 65 years were related to POMC. In multivariate analyses, sarcopenia (odds ratio = 3.039; 95% confidence interval 1.008-9.174; p = 0.048) and advanced age (odds ratio = 3.246; 95% confidence interval 1.078-9.803; p = 0.036) were found to be independent risk factors for POMC. CONCLUSIONS: This study showed that while sarcopenia is a risk factor for POMC, sarcopenia also prolongs the duration of ICU stay. Also sarcopenia has no effect on short-term mortality.

The importance of inflammatory biomarkers, IL-6 and PAPP-A, in the evaluation of asymptomatic apical periodontitis.

To examine the use of IL-6 and PAPP-A along with the new imaging for scoring methods to determine the severity of apical periodontitis (AP). The scoring of disease severity in 121 patients with AP, using dental radiographs, was based on "The Apical Periodontitis Grading Scale" (APGS), as those having 1 tooth with AP and severity of 3-4 were classified as grade 1 (mild); those having > 1 tooth and severity of 3-4 as grade 2 (moderate) and those with at least one tooth with a severity of 5 as grade 3 (severe). 45 systematically and orally healthy volunteers were selected as the control group (grade 0). Dental demographic data of all participants were recorded. Besides, venous blood samples were collected to study their complete blood count and levels of IL-6 and PAPP-A. Both NLR and PAPP-A levels of the grade 3 AP patients were found significantly higher than those of the control group and grade 1 and grade 2 AP patients (2.55 ± 1.40 vs 1.98 ± 1.05, 1.94 ± 0.58 and 1.86 ± 0.50; 0.606 ± 0.211 vs 0.422 ± 0.273, 0.447 ± 0.224 and 0.436 ± 0.242, p < 0.01, respectively). AP grades identified by the new scoring system were moderately correlated with IL-6 levels (Spearman r = 0.4168, p < 0.001). The risk of patients with IL-6 levels above 12.5 pg/ml to develop AP (relative risk) was found to be 2.19 times higher than that in those with lower IL-6 levels (98% Cl 1.233-3.905, p < 0.0024). APGS classification suggested to determine AP severity was found to be significantly correlated with levels of inflammatory markers IL-6 and PAPP-A.

Investigation of JAM-A (rs790056) and LFA-1 (rs8058823) gene variants in Turkish colorectal cancer patients.

BACKGROUND/AIMS: Lymphocyte function-associated antigen 1 (LFA-1) is a transmembrane glycoprotein expressed on the surface of leukocytes and containing the binding domain for junctional adhesion molecule-A (JAM-A). The aim of the present study was to evaluate the effects of JAM-A and LFA-1 variants on the formation of colorectal cancer and metastasis. MATERIALS AND METHODS: A total of 82 subjects with colorectal cancer and 67 healthy subjects were studied. DNA was isolated from blood samples, and variations were determined using the polymerase chain reaction and restriction fragment length polymorphism method. RESULTS: JAM-A rs790056 CC genotype and C allele were found to be higher in the colorectal cancer group (p<0.05), and approximately 3-fold increased colorectal cancer risk with CC genotype was determined (p=0.029). Haplotype analysis showed that GC haplotype (LFA-1 rs8058823G and JAM-A rs790056C) frequency was significantly higher in the patient group (p=0.041) than in controls. CONCLUSION: JAM-A rs790056 variation may be effective in the development of colorectal cancer.

Our experience with dermal substitute Nevelia® in the treatment of severely burned patients.

BACKGROUND: This research aims to retrospectively evaluate the effectiveness and safety of dermal substitute (DS), Nevelia®, for the treatment of severely burned patients. METHODS: Twenty severely burned patients were enrolled in this study between May 2017 and May 2018. After escharotomy of the wound, the treatment protocol was applied following a two-step procedure -DS implantation followed by split-thickness skin graft (STSG) application. Need for surgery, complications, hospitalisation duration and overall survival were analysed. RESULTS: Mean age was 40.1±4 (18-86) years old; female/male: 5/15. Mean burn surface area was 50.1%±2 (25-96). Two patients died under hospital treatment due to the severity of their burn trauma and comorbidities. For the rest of the cases, STSG was performed after Nevelia® at mean 21.2 days. No complications due to Nevelia® were detected. The patients were discharged with a mean total recovery of 55.2±4 days. CONCLUSION: This study showed that Nevelia® can be used safely and effectively in severely burned patients with low complication rates and short hospital stay.

Protective effects of resveratrol on hepatic ischemia reperfusion injury in streptozotocin-induced diabetic rats.

Resveratrol (RSV) is a natural polyphenolic compound having antioxidant effects. This study was designed to investigate the protective effects of resveratrol against oxidative stress in hepatic ischemia-reperfusion (I/R) injury in streptozotocin (STZ)-induced diabetic rats. STZ was injected intraperitonally (i.p.) to 18 Sprague-Dawley albino rats, which were divided into three groups, each having six rats. First group was non-treated diabetic group (D), second diabetic group was subjected to 30 min of hepatic ischemia followed by a 45-min reperfusion period (D + I/R), and third diabetic group was subjected to 30 min of hepatic ischemia followed by a 45-min reperfusion period and treated with 20 mg/kg/day oral RSV before 30 min I/R injury (D + I/R + RSV). At the end of the experimental period, animals were decapitated, and blood samples were collected to determine tissue tumor necrosis factor-α (TNF-α) levels. Liver and lung tissue samples were obtained for the evaluation of biochemical parameters including malondialdehyde (MDA) and glutathione (GSH) levels and histopathological examinations. Compared to control, I/R injury resulted in decreases in GSH levels and increases in MDA levels. Tissue TNF-α levels were also increased in the D + I/R group compared to D group. Treatment with RSV prevented the alterations on biochemical parameters and histopathological changes induced by I/R. We demonstrate that in diabetic rats, hepatic I/R injury is associated with an augmented inflammatory response and oxidative stress, while RSV pre-treatment significantly decreased these responses. Larger clinical studies are desirable to determine the exact role(s) of RSV on hepatic I/R injury among diabetic subjects.

Low Oxalobacter Formigenes Colonization is Associated with Reduced Bone Mineral Density in Urinary Stone Forming Patients.

INTRODUCTION: Lower bone mineral density (BMD) and reduced Oxalobacter formigenes colonization are common findings in urolithiasis patients. But none of the studies conducted investigated the relationship between decreased bone mineral density and reduced Oxalobacter colonization. Here we evaluated the relation between BMD and O. formigenes colonization in urolithiasis patients. MATERIALS AND METHODS: 50 stone formers (48.9 ± 11.9 years) and 50 control (47.2 ± 13.4 years) adult male subjects were included in the study. Alterations in O. formigenes colonization were determined as absolute O. formigenes count from fecal samples by real time polymerase chain reaction using species specific primers. BMD was evaluated from t- and z- scores calculated by using dual energy absorptiometry in the total femoral neck and lumbar spine (L2-L4). RESULTS: Low BMD was observed in 18 (36%) urinary stone forming patients and in 7 (14%) control subjects in the lumbar area (p < 0.05). The mean O. formigenes count in stone formers and control subjects were 19,257 (5,791 ± 1,117.93) and 143,850 (2,815,725 ± 3,946,044.7) (p < 0.05) respectively. We observed a correlation between decreased lumbar BMD and O. formigenes colonization and testosterone levels in stone formers. Our results indicated that diminished O. formigenes colonization in the gut of urinary stone forming subjects was associated with reduced BMD.

The alterations in adenosine nucleotides and lactic acid levels in striated muscles following death with cervical dislocation or electric shock.

In this study, changes in adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP) and lactic acid levels in masseter, triceps, and quadriceps muscles obtained from right and left sides of Spraque-Dawley rats following two different types of death were investigated. The samples were taken immediately and 120 minutes after death occurred either by cervical dislocation or electric shock. ATP concentrations in the muscles of masseter, triceps, and quadriceps were lower in samples obtained 120 minutes after death than that of samples obtained immediately after death. ADP, AMP, and lactic acid concentrations in these muscles were higher in samples obtained 120 minutes after death than those obtained immediately after death. A positive linear correlation was determined between ATP and ADP concentrations in quadriceps muscles of the rats killed with cervical dislocation and in masseter muscles of the rats killed with electric shock. When the rats killed with cervical dislocation and with electric shock were compared, ADP, AMP, and lactic acid concentrations were lower in the former than in the latter for both times (immediately and 120 minutes after death occurred). In the case of electric shock, ATP is consumed faster because of immediate contractions during death, resulting in a faster rigor mortis. This finding was confirmed with higher lactic acid levels in muscles of the rats killed with electric shock than the other group. In the cervical dislocation and electric shock group rats, ATP decreased in different levels in the three different muscle types mentioned above, being much decline in masseter in cervical dislocation and in quadriceps in electric shock group. This may be caused by low mass and less glycogen storage of masseter and by near localisation of electrode to quadriceps. One can conclude that the occurrence of rigor mortis is closely related to the mode of death.

The alterations in adenosine nucleotides and lactic acid in striated muscles of rats during Rigor mortis following death with drowning or cervical dislocation.

In this study, adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP) and lactic acid in the muscles of masseter, triceps, and quadriceps obtained from right and left sides of Spraque-Dawley rats following death were investigated. The samples were taken immediately and 120 minutes after death occurred. The rats were killed either by cervical dislocation or drowning. ATP concentrations in the muscles of masseter, triceps, and quadriceps were lower in samples obtained 120 minutes after death than in those obtained immediately after death. ADP, AMP, and lactic acid concentrations in these muscles were higher in samples obtained 120 minutes after death than those obtained immediately after death. A positive linear correlation was determined between ATP and ADP concentrations in quadriceps muscles of the rats killed with cervical dislocation and in triceps muscles of the rats killed with drowning. When rats killed with cervical dislocation and with drowning were compared, ADP, AMP, and lactic acid concentrations were lower in the former than in the latter for both times (immediately and 120 minutes after death occurred). In the case of drowning, ATP is consumed faster because of hard exercise or severe physical activity, resulting in a faster rigor mortis. Higher lactic acid levels were determined in muscles of the rats killed with drowning than the other group. In the control and electric shock rats, ATP decreased in different levels in the three different muscle types mentioned above in control group, being much decline in masseter and then in quadriceps. This may be caused by lower mass and less glycogen storage of masseter. No different ATP levels were measured in drowning group with respect to the muscle type possibly because of the severe activity of triceps and quadriceps and because of smaller mass of masseter. One can conclude that the occurrence of rigor mortis is closely related to the mode of death.