Investigation of Trpa1 and Trpc1 Immunreactivities in Colon Adenocarcinomas.

Purpose: As the normal colon epithelium differentiates into adenoma, invasive cancer and metastatic cancer, the cell acquires new characteristics such as apoptosis, proliferation, differentiation, invasion and metastasis. Many mechanisms are effective in acquiring these qualities. One of these is the regulation of the functioning of ion channels. This study aimed to examine TRPA1 and TRPC1 expression in colorectal adenocarcinomas showing different degrees of differentiation. Patients and Methods: We examined the biopsy specimens of 60 patients diagnosed with colorectal adenocarcinomas, including those of patients with well-differentiated (n = 20), moderately differentiated (n = 20) and poorly differentiated (n = 20) carcinomas. Moreover, 20 biopsy specimens of individuals with normal colonic mucosa were examined. Histoscores were calculated for TRPA1 and TRPC1 based on the extent of diffusion and intensity of immunoreactivity, and these scores were compared statistically. Results: A statistically significant increase in both TRPA1 and TRPC1 immunoreactivity was observed in low-grade and high-grade colon adenocarcinomas compared to the control group (p<0.001). A statistically significant decrease in both TRPA1 and TRPC1 immunoreactivity was observed in high-grade colon adenocarcinomas compared to low-grade colon adenocarcinomas (p<0.001). Conclusion: TRPA1 and TRPC1 immunoreactivites are increased in colorectal adenocarcinoma tissue compared with the healthy tissue. Furthermore, the immunoreactivity decreases as the grade of cancer increases.

Investigation of Hyaluronan Synthase 2 and CD44 immune reactivity as a biomarker to predict Progesterone-Resistant Endometrial Hyperplasia without atypia: A retrospective case-control study.

BACKGROUND/AIMS: In our study, the effect of hyaluronan synthase 2 (HAS2) and CD44 immunoreactivity as a predictive biomarker in the prediction of progesterone-resistant endometrial hyperplasia (EH) cases without atypia was investigated. SETTINGS AND DESIGN: In this retrospective study, HAS2 and CD44 immunoreactivity in the endometrial tissues of 60 patients diagnosed with EH and treated with progesterone and 20 patients diagnosed with proliferative endometrium (PE) were evaluated. MATERIALS AND METHODS: Eighty patients were divided into four groups. Group 1 (G1) (n = 20) = PE group, G2 (n = 20) = EH group without atypia, G3 (n = 20) = group with continued EH with treatment, G4 (n = 20) = EH with treatment without atypia. STATISTICAL ANALYSIS: Intergroup evaluation was done with One-way ANOVA and posthoc tukey test. P < 0.05 values were considered statistically significant. RESULTS: The HAS2 immunoreactivity score of G2 and G3 was higher than G1 and G4. On the other hand, there was no difference between G1 and G4. When G2 and G3 were compared, HAS2 immunoreactivity scores were significantly increased in G3. When CD44 immunoreactivity was compared with G1, a significant increase was detected in G2, G3, and G4. However, CD44 immunoreactivity scores were similar in G2, G3, and G4. CONCLUSION: HAS2 immunoreactivity may be an immunohistochemical biomarker in predicting EH cases without atypia resistant to progesterone therapy. Since CD44 immunoreactivity is increased in all EH groups without atypia, it is not effective in predicting treatment resistance.

The Effect of Thymoquinone on the TNF-α/OTULIN/NF-κB Axis Against Cisplatin-Induced Testicular Tissue Damage.

One of the adverse effects of the antineoplastic drug cisplatin (CS) is damage to testicular tissue. This study aimed to examine the potential therapeutic effect of thymoquinone (TQ), a strong antioxidant, against testicular damage caused by CS. In the experiment, 28 rats were used, and the rats were randomly divided into four groups: control (n = 7), CS (n = 7), CS + TQ (n = 7), and TQ (n = 7). The experiment was called off after all treatments were finished on day 15. Blood serum and testicular tissues were utilized for biochemical, histological, immunohistochemical, mRNA expression, and gene protein investigations. The testosterone level decreased and oxidative stress, histopathological damage, dysregulation in mitochondrial dynamics, inflammation and apoptotic cells increased in testicular tissue due to CS administration. TQ supplementation showed anti-inflammatory, antioxidant, and anti-apoptotic effects in response to CS-induced testicular damage. In addition, TQ contributed to the reduction of CS-induced toxic effects by regulating the TNF-α/OTULIN/NF-κB pathway. TQ supplementation may be a potential therapeutic strategy against CS-induced testicular damage by regulating the TNF-α/OTULIN/NF-κB axis, inhibiting inflammation, oxidative stress, and apoptosis.

Determination of M1/M2 Macrophage Polarization in Ipsilateral and Contralateral Rat Testis Tissue Following Unilateral Torsion/Detorsion.

The present study investigates the changes in M1/M2 macrophage polarization resulting from unilateral testicular torsion in the bilateral testis. The study sample included 63 male Sprague-Dawley rats, which were randomly divided into nine groups (n = 7): Control, Sham (4 h (4 h), 24 h, 7 days (7d), 14d), and Torsion/Detorsion (T/D) (4 h, 24 h, 7d, 14d). Histopathological evaluations revealed no changes in the Sham groups, while T/D was noted to cause edema, vascular occlusion, disruption of seminiferous tubule epithelial organization, germ cell abnormalities and structural anomalies in the experimental rats, the severity and extent of which increased from 4 h to 14d after T/D. The Cosentino scores used to determine the degree of histological damage were consistent with the histopathological findings in all groups, while the Johnsen scores, as a marker of spermatogenesis, were lower in the T/D groups. Seminiferous tubule diameters and germinal epithelial thickness decreased significantly in parallel with increased tubule damage in the ipsilateral testicles. Testicular torsion significantly affected sperm motility, with significant reductions observed in the T/D 7d and T/D 14d groups. A hormone profile analysis revealed decreased testosterone levels in both the Sham and T/D groups when compared to the Controls. CD68 and CD163 immunoreactivities, as M1 and M2 macrophage surface markers, were determined in the testicular tissue using the avidin-biotin-peroxidase complex method. T/D interventions caused M1/M2 macrophage polarization changes and increased M1 macrophages, particularly in contralateral testicular tissue. The increase in M1 macrophages in contralateral testicular tissue following T/D in the present study suggests that cell processes, including macrophages, may play an important role in contralateral testicular injury.

Use of Ozone Therapy and Thymoquinone in the Prevention of Formaldehyde Toxicity by Inhalation: An Experimental Study.

INTRODUCTION: The study determined the damage caused by formaldehyde (FA) exposure in blood and liver samples using biochemical markers. Histopathological analysis was performed using the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) method and measurement of CD68 cell density. To what extent the antioxidant molecules thymoquinone (TQ) and ozone (O3) reversed the damage caused by FA exposure was investigated, both when used alone and combined. METHODS: Fifty-six Sprague-Dawley male rats of eight to ten weeks of age were used in the experiment. The rats were divided into eight groups, with seven rats in each group: the untreated control group, the group treated with TQ (10 mg/kg/day), the group treated with O3 (150 µg/kg/day), the group treated with TQ+O3, the group exposed to FA (10 ppm 8 h/day), the group receiving FA+TQ, the group receiving FA+O3, and the group receiving FA+TQ+O3. Serum aspartate transaminase (AST), alanine transaminase (ALT), total antioxidant (TAS, U/mL), and total oxidant (TOS, nmol/mL) levels were analyzed. TAS and TOS levels, CD68 cell density, and apoptotic cells were determined in liver tissues. RESULTS: FA exposure caused an increase in serum AST and ALT levels of (p<0.05) experimental animals, a decrease in TAS levels in serum (p=0.03) and liver (p>0.05) and an increase in TOS levels (p>0.05), TUNEL positivity (p<0.001), and CD68 cell density (p=0.004). Administration of TQ and O3 as antioxidants significantly reversed biochemical and histopathological alterations in the serum and liver. CONCLUSION: TQ and ozone therapy suppressed oxidative stress caused by FA exposure and reversed the emerging histopathological deteriorations. Ozone therapy did not suppress the effects of TQ. Therefore, ozone therapy can be given as a supportive therapy along with the main therapeutic agents. We think TQ and ozone therapy may be useful to protect individuals exposed to FA.

Effects of N-acetylcysteine on spexin immunoreactivity in kidney tissues of rats treated with adriamycin.

Objectives: Due to its negative side effects, mainly nephrotoxicity, adriamycin (ADR) is used fairly infrequently. The purpose of this study is to investigate the effects of N-acetyl cysteine (NAC) on the immunoreactivity of spexin (SPX) in the kidney tissues of rats given ADR. Materials and Methods: A total of 28 male Sprague-Dawley rats were randomly assigned to four groups (n=7): control (no intervention), NAC (150 mg/kg/day, administered intraperitoneally), ADR (single dose of 15 mg/kg, administered intraperitoneally), and ADR+NAC (single dose of 15 mg/kg ADR + 150 mg/kg/day NAC, both administered intraperitoneally). The experiment was concluded on the 15th day. Results: The administration of ADR resulted in biochemical and histopathological alterations in the kidney. It was found that ADR treatment led to elevated levels of TOS (total oxidative stress), apoptosis, and SPX. Conversely, when NAC was administered as a treatment, it effectively reduced TOS, apoptosis, and SPX levels. These findings suggest that SPX may contribute to the development of ADR-induced kidney damage. Conclusion: Further investigations are warranted to gain a comprehensive understanding of kidney damage, and specifically to elucidate the role of SPX in this context. Additionally, these studies can pave the way for exploring novel therapeutic strategies targeting SPX to prevent and/or treat the development of kidney damage.

Role of asprosin and meteorin-like peptide in progression of actinic keratosis to squamous cell carcinoma.

Squamous cell carcinoma (SCC) often develops from an underlying premalignant lesion. Factors that affect the progression of actinic keratosis (AK) to invasive SCC are not fully known. Asprosin (ASP) and meteorin-like peptide (METRNL) are adipokines that are involved primarily in glucose metabolism. We investigated the expression of ASP and METRNL in AK and SCC to evaluate the role of these adipokines in the development of SCC. We used 15 SCC specimens, 12 AK specimens and 12 healthy control skin specimens. ASP and METRNL protein expression in tumor and surrounding tissue was evaluated using immunohistochemistry. ASP expression in tumor tissue was significantly greater in the SCC group than in the control and AK groups, but it did not differ significantly between the AK and control groups. A positive correlation was observed for both ASP and METRNL expressions between tumor tissue and adjacent epidermis, hair follicles, sebaceous gland, eccrine gland, inflammatory cells and vascular structures. ASP and METRNL may exert pro-tumor effects toward development of invasive SCC. The expression intensity of ASP and METRNL can be used as a biomarker of risk of progression to SCC.

Resveratrol may dose-dependently modulate nephrin and OTULIN levels in a doxorubicin-induced nephrotoxicity model.

One of the most important side effects of Doxorubicin (DOX), a chemotherapeutic agent, is nephrotoxicity. The purpose of this study is to determine whether different doses of natural polyphenol Resveratrol (RSV) show antioxidative, anti-inflammatory or antiapoptotic effects in kidney tissue in DOX-induced nephrotoxicity and to detect how nephrin and OTULIN levels are affected in this process. A total of six equal groups made up of the 42 Sprague-Dawley rats utilized in the study (n = 7) were randomly assigned. Except for the control group (no treatment), all treatments were given intraperitoneally to the DOX (15 mg/kg), DOX + RSV I (15 mg/kg DOX+ 1 mg/kg/day RSV), DOX + RSV II (15 mg/kg DOX+ 5 mg/kg/day RSV), RSV I and RSV II groups. Kidney tissues taken from rats sacrificed on the fifteenth day were analyzed biochemically, histologically and immunohistochemically. Accordingly, it was determined that nephrin and OTULIN levels decreased in kidney tissue in DOX-induced nephrotoxicity. Furthermore, DOX caused oxidative stress, inflammation, and apoptosis, as well as histopathological changes in kidney tissue. However, it was observed that DOX-induced changes were regulated by RSV application. RSV was demonstrated to have antioxidant, anti-inflammatory and anti-apoptotic properties in dose-dependent DOX-induced nephrotoxicity. RSV may exert nephroprotective effects by modulating DOX-induced altered nephrin and OTULIN levels.

Effects of irisin and exercise on adropin and betatrophin in a new metabolic syndrome model.

Metabolic syndrome (MetS) is a prevalent public health problem. Uric acid (UA) is increased by MetS. We investigated whether administration of UA and 10% fructose (F) would accelerate MetS formation and we also determined the effects of irisin and exercise. We used seven groups of rats. Group 1 (control); group 2 (sham); group 3 (10% F); group 4 (1% UA); group 5 (2% UA); group 6 (10% F + 1% UA); and Group 7, (10% F + 2% UA). After induction of MetS (groups 3 -7), Group 3 was divided into three subgroups: 3A, no further treatment; 3B, irisin treatment; 3C, irisin treatment + exercise. Group 4, 1% UA, which was divided into three subgroups: 4A, no further treatment; 4B, irisin treatment; 4C, Irisin treatment + exercise. Group 5, 2% UA, which was divided into three subgroups: 5A, no further treatment; 5B, irisin treatment; 5C, irisin treatment + exercise. Group 6, 10% F + 1% UA, which was divided into three subgroups: 6A, no further treatment; 6B, irisin treatment; 6C, irisin treatment + exercise. Group 7, 10% F + 2% UA, which was divided into three subgroups: 7A, no further treatment; 7B, irisin treatment; 7C, irisin treatment + exercise., Irisin was administered 10 ng/kg irisin intraperitoneally on Monday, Wednesday, Friday, Sunday each week for 1 month. The exercise animals (in addition to irisin treatment) also were run on a treadmill for 45 min on Monday, Wednesday, Friday, Sunday each week for 1 month. The rats were sacrificed and samples of liver, heart, kidney, pancreas, skeletal muscles and blood were obtained. The amounts of adropin (ADR) and betatrophin in the tissue supernatant and blood were measured using an ELISA method. Immunohistochemistry was used to detect ADR and betatrophin expression in situ in tissue samples. The duration of these experiments varied from 3 and 10 weeks. The order of development of MetS was: group 7, 3 weeks; group 6, 4 weeks; group 5, 6 weeks; group 4, 7 weeks; group 3, 10 weeks. Kidney, liver, heart, pancreas and skeletal muscle tissues are sources of adropin and betatrophin. In these tissues and in the circulation, adropin was decreased significantly, while betatrophin was increased significantly due to MetS; irisin + exercise reversed this situation. We found that the best method for creating a MetS model was F + UA2 supplementation. Our method is rapid and simple. Irisin + exercise was best for preventing MetS.

Effects of Vitamin D on Asprosin Immunoreactivity Against Cyclophosphamide-Induced Liver Injury in Rats.

Background Cyclophosphamide (CP), commonly used as an anticarcinogenic drug, has the potential to induce detrimental effects on multiple tissues, including the liver. Asprosin, which is a glucogenic adipokine, induces the liver to secrete glucose, thus contributing to the maintenance of homeostasis. This study aims to investigate the immunoreactivity of asprosin in the liver tissue of rats exposed to CP administration, as well as the changes in its levels due to the supplementation of Vitamin D (Vit D). Materials and methods Four experimental groups were formed, including control, Vit D (200 IU/kg), CP (200 mg/kg), and Vit D+ CP. Histopathological analysis was carried out by employing staining methods on liver tissues. These techniques encompassed the application of hematoxylin-eosin (H&E), Masson's trichrome, and periodic acid Schiff (PAS). Through the application of spectrophotometric methods, concentrations of malondialdehyde (MDA), total antioxidant status (TAS), total oxidant status (TOS), and asprosin were determined. Furthermore, apoptotic cells were identified by the terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL) method, and the asprosin immunoreactivity was determined by immunohistochemistry. Results Under light microscope examination, the histopathological damage was found to be more notable in the CP group compared to the control group. Moreover, a decrease was observed in serum and tissue asprosin levels, while an increase was noted in the count of apoptotic cells, along with elevated MDA and TOS levels. However, in the CP+Vit D group, Vit D administration alleviated histopathological damage. Notably, there were significant increases in TAS and asprosin levels, accompanied by reductions in both MDA and TOS levels. Conclusions The effect of CP on liver tissue was observed to result in damage and a reduction in asprosin levels. Vit D supplementation revealed elevated asprosin levels and a distinct protective effect on the tissue. Considering the association between asprosin and liver injury induced by CP, further research is needed to elucidate the mechanisms that underlie the effect of asprosin on tissues. When combined with Vit D, asprosin holds promise for potential clinical applications as a therapeutic target.

N-Acetylcysteine may exert hepatoprotective effect by regulating Meteorin-Like levels in Adriamycin-induced liver injury.

Adriamycin (ADR) is an important chemotherapeutic drug, but it has serious side effects such as hepatotoxicity. This study aimed to evaluate whether N-acetylcysteine (NAC) has hepatoprotective effects against ADR-induced hepatotoxicity in rats. In addition, it was aimed to determine how Meteorin-Like (MtrnL), which has pleiotropic effects on immunology, inflammation, and metabolism, is affected by ADR and/or NAC applications in liver tissue. 28 rats were randomly assigned to one of four equal groups in the study: control (no treatment), NAC (150 mg/kg/day of NAC intraperitoneally (i.p), ADR (15 mg/kg only on the first day of the experiment), and ADR + NAC (ADR 15 mg/kg on the first day of the experiment + 150 mg/kg/day NAC i.p). After 15 days, liver enzyme levels in serum, oxidant/antioxidant parameters in liver tissue, histopathological changes, caspase 3 (Casp3) and heat shock protein 70 (HSP-70) immunoreactivities, and MtrnL levels were examined. Histopathological changes, liver enzyme levels, as well as HSP-70, and Casp3 immunoreactivities increased due to ADR application. Additionally, MtrnL levels in liver tissue were significantly increased as a result of ADR application. However, it was detected that the NAC application significantly regulated the ADR-induced changes. Furthermore, it was determined that NAC administration regulated the changes in ADR-induced oxidative stress parameters. We propose that NAC may exert a hepatoprotective effect by regulating ADR-induced altered oxidative stress parameters, MtrnL levels, Casp3, and HSP-70 immunoreactivities in the liver.

Fibulin1 and mesothelin expressions in pancreas ductal adenocarcinoma.

OBJECTIVE: The balance between malignant tumor cells and the connective tissue surrounding them determines the aggressiveness of the tumor. We aimed to understand the effects of mesothelin (MSLN) and fibulin1 (FBLN1) expressions on survival in pancreas ductal adenocarcinoma (PDCA), and also whether these proteins have prognostic value for PDCA. METHODS: Of 80 patients in total, 40 who underwent the Whipple procedure for diagnosed PDCA between 2009 and 2016, and 40 patients with diagnosed pancreatitis as the control group, were included in the present study. Immunohistochemically, MSLN, and FBLN1 expressions were evaluated retrospectively. We assessed the relationship between the degree of MSLN, FBLN1 expression, clinical-pathological features, and survival rates in PDCA cases. RESULTS: The median follow-up duration was 11.4 (3-41) months. All of the patients for MSLN and FBLN1 were immune reactive. We detected a significant difference in MSLN expression between patients with PDCA and control groups, but not in FBLN1 expression. MSLN, FBLN1 expressions were categorized as lower-higher (L/H) groupings. There was no difference in the median overall survival (OS) of patients in the MSLN groups. The L-FBLN1 group had a median OS of 18 months (95% CI: 9.51-26.48) versus 14 months (95% CI: 13.021-14.97) in the H-FBLN1 group (interconnective tissue) (p=0.035). According to Kaplan-Meier analysis, L-FBLN1 expression in the tumor microenvironment was associated with longer survival in PDCA. The FBLN1 expression in the tumor microenvironment was shown to be significantly inversely related to OS (p=0.05). CONCLUSION: The FBLN1 expression, which is in the tumor microenvironment of PDCA, may serve as a prognostic biomarker.

The Effects of N-acetylcysteine on Transient Receptor Potential Melastatin 2 Channels Activation and Expression in Testicular Tissue of Diabetic Rats.

INTRODUCTION: Diabetes mellitus (DM) is a common, chronic metabolic disease that has harmful effects on many diverse tissues, including the testis. One of the ways of tissue damage is the modification of transient receptor potential melastatin 2 (TRPM2) channels by increased reactive oxygen species (ROS). In our study for the first time, it was aimed to investigate TRPM2 channel activation in testicular tissues of diabetic rats induced by streptozotosin (STZ) and to examine the efficacy of N-acetylcysteine (NAC) treatment, which is an antioxidant. METHODS: In our study, 28 Wistar albino male rats aged 8-10 weeks were used, and animals were divided into four groups: control group, NAC group, DM group, and DM + NAC group. The experimental phase was designed as eight weeks. The malondialdehyde (MDA) level, which is an indicator for lipid peroxidation due to oxidative stress, was measured by the spectrophotometric method. The Tunel assay was used to determine apoptosis on testicular tissue. TRPM2 immunoreactivity was determined by the avidin-biotin-peroxidase complex method, and quantitative polymerase chain reaction (QPCR) was used to determine TRPM2 expression levels. RESULTS: It was seen that MDA levels were significantly increased in the DM group and decreased after NAC treatment. Similarly, it was observed that apoptosis levels, which increased significantly in diabetic rats, decreased to the levels of the control group after treatment. It was seen that TRPM2 activation and expression levels were significantly decreased in the DM group. CONCLUSION:  The results of this study show that NAC regulates TRPM2 activation in the testicular tissue of patients with diabetes and has tissue-protective properties.

TRPM2 may be involved in high fructose corn syrup-induced anxiety-like behavior in adult male rats.

Excessive high fructose corn syrup (HFCS) consumption is known to cause oxidative stress, which induces transient receptor potential melastatin type 2 (TRPM2) channel gating. Oxidative stress-induced TRPM2 gating is suggested to play an important role in neurons, indicating a role for the TRPM2 channel in a variety of neuropsychiatric disorders including depression and anxiety. We investigated the effects of HFCS and chronic immobilization stress (CIS) on TRPM2 channel immunoreactivity, anxiety, and depressive-like behaviors in adult male rats. The male rats (n=8/group) were divided into 4 groups: Control, 20% HFCS (F20), 40% HFCS (F40), and stress. The control group received tap water, and F20 and F40 groups were exposed to HFCS 20% and 40% respectively for 14 consecutive days. Rats in the stress group were subjected to immobilization stress for 3 or 6 hours daily in the first and second weeks to induce CIS. Then, light/dark tests, open field tests (OFT), and tail suspension tests (TST) were performed, respectively. In the light/dark test, the time spent in the dark chamber significantly increased in all groups vs the control group (P<0.01). In support of this result, time spent in the light chamber significantly decreased in all groups vs the control group (P<0.01). Besides, CIS significantly increased depressive-like behavior in the stress group vs the control group (P<0.05). In serum hormone levels, corticosterone (CORT) levels significantly increased in the F40 and stress groups vs the control group (P<0.01). TRPM2 immunoreactivity significantly increased in the hippocampus, prefrontal cortex (PFC), nucleus accumbens (NaC), and amygdala regions by HFCS and CIS treatments. For the first time in the present study,  showed that f increased immunoreactivity of the TRPM2 cation channels may be linked to the anxiety-like behavior induced by HFCS.

Activation of Nrf-2 Transcription Factor and Caspase Pathway with Royal Jelly Reduces Fluoride Induced Testicular Damage and Infertility in Rats.

This study was carried out to investigate the protective properties of royal jelly on the testicular tissue of rats with testicular damage by giving fluoride. Sperm motility, epididymal sperm density and abnormal sperm ratios were examined and visualized with a light microscope. Expression levels of Caspase-3, Bcl-2, Nrf-2, NF-κB, COX-2, TNF-α and IL1-α proteins in testis tissue were determined by western blot technique. As a result of the study, MDA level, expression level of Bcl-2, NFÒ¡B, COX-2, TNF-α and IL1-α proteins, abnormal sperm rates were found higher in Fluoride-50 and Fluoride100 groups compared to other groups. In addition GSH, Catalase enzyme levels, expression levels of Caspase-3 and Nrf-2 proteins were found to be higher in Fluoride + Royal Jelly groups compared to Fluoride-50 and Fluoride-100 groups. In addition, lower degeneration of testicular tissue was found in the histological evaluation in the Fluoride + Royal Jelly groups compared to the other groups. When the data are evaluated royal jelly provides effective protection against testicular damage. From this point of view, we hope that similar results will be obtained when royal jelly is tested on humans.

Asprosin, irisin, and meteorin-like protein immunoreactivity in different stages of colorectal adenocarcinoma.

OBJECTIVE: In this study, we aimed to investigate the immunoreactivity of asprosin, irisin, and meteorin-like protein (METRNL) in different stages of colorectal adenocarcinoma, which is the most common malignancy of the gastrointestinal tract. MATERIALS AND METHODS: Overall, 60 patients with colorectal adenocarcinoma, including 20 well (Group 1), moderately (Group 2), and poorly differentiated (Group 3) cases, respectively, and 20 with normal colonic mucosa, were examined using light microscopy for immunohistochemical staining of asprosin, METRNL, and irisin. RESULTS: Compared with the control group, a significant increase in irisin and asprosin immunoreactivity was found in the grade 1 and 2 colorectal adenocarcinoma groups. Moreover, compared with the grade 1 and 2 groups, this immunoreactivity was significantly decreased in the grade 3 colorectal adenocarcinoma group. Although there was no significant difference in METRNL immunoreactivity between the grade 1 and control groups, a statistically significant increase in this immunoreactivity was found in the grade 2 group. In contrast, METRNL immunoreactivity was significantly decreased in the grade 3 group compared with the grade 2 group. CONCLUSION: We found that in early-stage colorectal adenocarcinoma there was an increase in the immunoreactivity of asprosin and irisin, but in the advanced stage there was a decrease in immunoreactivity. Although METRNL immunoreactivity did not change in the control and grade 1 groups, it was found to increase significantly in the grade 2 group and decrease in the grade 3 group.

N-Acetylcysteine May Regulate Altered Meteorin-Like Levels in Testicular Tissue due to Aluminum Exposure.

Aluminum (AL) is a heavy metal known to have toxic effects on the reproductive system. It is known that N-acetylcysteine (NAC), which has an antioxidant effect, is a useful chelator for heavy metals. This study aimed to determine whether NAC may reduce AL-induced oxidative stress, inflammation, and germ cell apoptosis in testicular tissues and its effects on meteorin-like (METRNL) levels, which are known to play a role in energy metabolism. In this experimental study, 28 Sprague-Dawley male rats were randomly divided into 4 groups (n = 7): control, AL (30 mg/kg/day AL), AL + NAC (30 mg/kg/day AL + 150 mg/kg/day NAC), and NAC (150 mg/kg/day NAC). All AL and NAC applications were performed intraperitoneally for 14 days. At the end of the experiment, the effects of AL and/or NAC applications on testicular tissue were examined histomorphometrically, histopathologically, immunohistochemically, and biochemically. It was determined that AL exposure caused histomorphometric and histopathological changes, oxidative stress, apoptosis of germ cells, and inflammation in testicular tissues. In addition, AL caused an increase in METRNL levels. It was determined that NAC treatment significantly reduced the negative effects of AL. NAC therapy may be a protective strategy in reproductive toxicity due to AL exposure.

The investigation of cholinergic receptor muscarinic 1 activity in the rat ovary with induced ovarian hyperstimulation.

Objective: We look at the immunoreactivity of cholinergic receptor muscarinic 1 (CHRM1) in the ovarian tissues of rats with ovarian hyperstimulation syndrome (OHSS) considering the possibility that the muscarinic activity may contribute to the pathophysiology of OHSS. Materials and Methods: In this study, 14 immature female Wistar Albino rats were divided into two groups at random. The rats were 22 days old. Rats in the control group (n=7) were 22 days old, while those in the OHSS group (n=7) received 10 IU follicle-stimulating hormone subcutaneously over the course of four days and 30 IU human chorionic gonadotropin (hCG) on the fifth day to induce ovarian hyperstimulation. All the rats were sacrificed after all the groups' ovaries and blood samples were collected at the conclusion of the experiment. The left ovarian tissues were kept in aluminum foil at -80 °C, while the right ovarian tissues were kept in 10% formalin. Tissue vascular endothelial growth factor (VEGF), interleukin (IL)-1ß, IL-6, IL-10, tumor necrosis factor (TNF)-α and malondialdehyde (MDA) levels were measured by The Enzyme Linked Immunosorbent Assay technique in the ovarian tissues. CHRM1 immunoreactivity was scored immunohistochemically. Results: Ovarian weight, tissue IL-10, TNF-α, VEGF and MDA levels, and CHRM1 immunoreactivity were significantly increased in the OHSS group. Conclusion: Increased levels of CHRM1 activity may play a role in the pathophysiology of OHSS. With further studies, the effect of luteinizing hormone and hCG on the ovarian and hypothalamic cholinergic system can be further investigated, and useful information can be obtained in determining OHSS prevention strategies.

N-Acetylcysteine and Benfotiamine Protect Autotransplanted Ovarian Tissue From Ischemia-Reperfusion Injury: An Experimental Study.

OBJECTIVES: This study aimed to compare the effects of N-acetylcysteine and benfotiamine in protection of ovarian tissue from ischemia caused by slow neovascularization injury due to intraperitoneal ovarian autotransplant in rats. MATERIALS AND METHODS: Twenty-eight female rats were divided into 4 groups, each containing 7 rats. Group 1 only had the abdomen opened and closed, group 2 was the transplant-only group, group 3 received benfotiamine for 3 weeks starting 1 day before the transplant procedure, and group 4 received N-acetylcysteine for 3 weeks starting 1 day before the transplant procedure. At the end of the experimental period, malondialdehyde levels in ovarian tissues together with the apoptosis and fibrosis, proliferating cell nuclear antigen and vascular endothelial growth factor immunoreactivity, and ovarian reserves were investigated. RESULTS: Apoptosis was significantly increased in group 2 animals. Primordial follicle count was higher in groups 3 and 4 than in group 2. Vascular endothelial growth factor immunoreactivity was decreased in groups 3 and 4 compared with group 2. Proliferating cell nuclear antigen immunoreactivity was reduced in the secondary follicles in all transplant groups. CONCLUSIONS: In autologous intraperitoneal ovarian transplant, both benfotiamine and N-acetylcysteine are equal and effective agents in protection of ovarian tissue against ischemic injury.

Asprosin and meteorin-like protein immunoreactivity in invasive ductal breast carcinoma stages.

AIM: The study aimed to investigate asprosin (ASP) and meteorin-like (METRNL) protein immunoreactivity in invasive ductal breast cancer. MATERIALS AND METHODS: Overall, 60 cases of invasive ductal breast cancer (20 cases each of Grade 1, 2 and 3) were evaluated in addition to 20 normal breast tissues obtained from the Pathology Department Archive. ASP and METRNL expressions were assessed using immunohistochemical staining and visualised under a light microscope. RESULTS: There was a significant difference in ASP and METRNL immunoreactivity among all the groups included in the study (p < 0.001). Cancer tissues with Grade 1, 2 and 3 showed a significant increase in ASP and METRNL immunoreactivity compared with the control group; however, no significant difference was noted among the cancer tissues with Grade 1, 2 and 3. CONCLUSIONS: ASP and METRNL immunoreactivity increased at the cellular level in invasive ductal breast cancer, but there was no difference in immunoreactivity among the breast cancer grades.