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.

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.

The knockdown of stathmin with si-RNA inhibits invasion of mesothelioma.

BACKGROUND: To investigate the mechanism of action of stathmin1 (STMN1) in mesothelioma (MSM) and whether it has any role in its treatment. METHODS: STMN1 expression was examined using immunohistochemistry in biopsy tissues taken from MSM patients. The relationships between the levels of STMN1 expression in the pathology preparations of MSM patients, and the clinicopathological characteristics of these patients, and their survival times were investigated. Transfection of STMN1-specific siRNA into SPC212 cells was compared to negative control siRNAs. The mRNA levels of genes that may play a role in invasion, apoptosis, and autophagy were evaluated by RT-PCR. RESULTS: The expression of STMN1 was shown to be high in MSM tissues (p < 0.05). It was found that the only independent predictor factor affecting the survival time of MSM patients was the disease stage (p < 0.05). STMN1 was significantly reduced after siRNA intervention (81.5%). STMN1 with specific siRNA has been shown to suppress invasion by reducing the mRNA levels of cadherin-6 (CDH6), fibroblast growth factor-8 (FGF8), hypoxia-inducible factor 1 (HIF1A), matrix metallopeptidase 1-2 (gelatinase A) (MMP1-2), and TIMP metallopeptidase inhibitor 2 (TIMP2), which are important markers for invasion. Although the expression of apoptosis and autophagy-related genes, caspase-2 (Casp2) and LC-3, was reduced by silencing STMN1 with specific siRNA in western blot analysis, this effect was not observed in PCR results. CONCLUSIONS: Immunohistochemical analysis of STMN1 may contribute to the differential diagnosis of MSM, and STMN1 may also be considered as a potential therapeutic target in the early invasive stage of MSM therapy.

Prognostic value of indoleamine 2, 3-dioxygenase-1 expression in glial tumors.

Background and purpose:

Gliomas are the most common primary malignant central nervous system tumors in adults, exhibiting a poor prognosis. Indoleamine 2, 3-dioxygenase-1 (IDO-1) has important functions in cancer immunotherapy due to its role in escaping cancer cells from the immune system. In this study we purposed to evaluate the correlation between IDO-1 expression and clinicopathological parameters in gliomas, and whether IDO-1 can be a prognostic marker.

n=75 patients in total, n=25 patients with low grade glial tumors (LGG, grade 1-2), n=25 patients with high grade glial tumors (HGG, grade 3-4), and n=25 persons with normal brain tissue as control group were included in this study. IDO-1 expression was categorized by using immunohistochemical staining in biopsy specimens as high (H) and low (L) groups among the patients with gliomas. We used a 95% percent confidence interval and p <0.05 to analyze the association between the degree of IDO-1 expression, clinicopathological characteristics, and survival rates in glioma patients. 

In HGG, IDO-1 levels were higher than in control brain tissue and LGG (p< 0.001). The mean overall survival (OS) was longer in the L-IDO-1 group (64.53 ± 3.34) in months (95% CI: 57.969-71.098) compared to the H-IDO-1 group (43.74 ± 4.36) in months, (95% CI: 35.218-52.330) (p< 0.05).

IDO-1 expression is an in­de­pendent prognostic biomarker to predict 
OS and progression in HGG. IDO-1 can be evaluated as an alternative instrument for precision medicine in the treatment of gliomas.

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.

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.

Do Histologically Aggressive Subtypes of Papillary Thyroid Microcarcinoma have Worse Clinical Outcome than Non-Aggressive Papillary Thyroid Microcarcinoma Subtypes? A Multicenter Cohort Study.

Histologically aggressive micropapillary thyroid carcinomas (PTMC) subtypes are thought to be associated with an aggressive clinical course. However, evidence for unfavorable clinical outcomes in patients with aggressive PTMC subtypes is not clear. In this study, we intended to determine the difference in clinical outcomes between patients with aggressive and non-aggressive PTMC subtypes. In this multicenter cohort study, the computer-recorded clinical and histopathological data of patients who underwent thyroid surgery between January 2000 - January 2021 in 9 referral centers and were diagnosed as PTMC were analyzed. A total of 1585 patients [female 1340 (84.5%), male 245 (15.5%), mean age 47.9±11.63 years), with a mean follow-up time of 66.55±37.16 months], were included in the study. Ninety-eight cases were diagnosed as aggressive and 1487 as non-aggressive subtypes. Persistent/recurrent disease was observed in 33 (33.7% )and 41 (2.8%) patients with aggressive and non-aggressive subtypes (p<0.001). Diseases-free survival rates were markedly lower in patients with aggressive than in those with non-aggressive PTMC subtypes (66.3 vs. 94.8%, log-rank p<0.001). Moreover, in multivariate analysis, aggressive histology was an independent predictor of persistent/recurrent disease, after controlling for other contributing factors (HR 5.78, 95% CI 3.32-10, p<0.001). Patients with aggressive PTMC subtypes had higher rates of incomplete biochemical and structural response than patients with non-aggressive subtypes as well (p<0.001). Aggressive PTMC subtypes share many characteristics with histologically identical tumors>1 cm in size. Therefore, the histopathological subtype of PTMC should be taken into consideration to tailor a personalized management plan.

Evaluation of the Effects of Dual Antiplatelet Therapy on Guided Bone Regeneration in Peri-Implant Bone Defect.

In this study, the authors aim to investigate the effect of dual antiplatelet agents on peri-implant-guided bone regeneraation by studying a sample of rats with titanium implants in their tibias. The rats were randomly divided into 5 groups: acetylsalicylic acid (ASA) (n=10), treated with 20 mg/kg of ASA; ASA+CLPD (Clopidogrel): (n=10), treated with 20 mg/kg of ASA and 30 mg/kg of clopidogrel; ASA+PRSG (Prasugrel): (n=10), treated with 20 mg/kg of ASA and 15 mg/kg of prasugrel; ASA+TCGR (Ticagrelor): (n=10), treated with 20 mg/kg of ASA and 300 mg/kg of ticagrelor; and a control group (n=10) received no further treatment after implant surgery. Bone defects created half of the implant length circumferencial after implant insertion and defects filled with bone grafts. After 8 weeks experimental period, the rats sacrified and implants with surrounding bone tissues were collected to histologic analysis; bone filling ratios of defects (%) and blood samples collected to biochemical analysis (urea, creatinine, aspartate aminotransferase, alanine aminotransferase, phosphorus, magnesium, alkaline phosphatase, calcium, and parathormone). A statistically significant difference was not detected between the groups for all parameters ( P >0.05). When the percentage of new bone formation was examined, it was found that there was no statistically significant difference between the groups ( P >0.05). Antiplatelet therapy may not adversely affect guided bone regeneration in peri-implant bone defects.

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.

The overexpression of cyclin D1 is a positive prognostic factor in advanced-stage breast carcinoma cases.

OBJECTIVE: Cyclin D1 (CDDN1) is a protein required for mitotic cell cycle progression through the G1 phase, as well as a regulatory component of the cyclin-dependent kinases CDK4 and CDK6. In this study, we wanted to evaluate the relationship between CDDN1 expression and clinicopathological features in breast cancer (BC) cases and whether CDDN1 could be used as a prognostic biomarker for BC cases. METHODS: A total of 70 cases, 30 cases each with limited and advanced-stage BC, and as the control group, 10 healthy breast tissue, without a cancer diagnosis, with examined for benign reasons (mammoplasty, breast reduction surgery, etc.) were included in this study. The pathological specimens from the cases were stained, immunohistochemically, and categorized as a "low" (L) group or a "high" (H) group for CDDN1 expression. The cases' clinicopathological features and survival rates were evaluated statistically, within a 95% of confidence interval, p<0.05, retrospectively. RESULTS: The median follow-up period of the cases was 48.00 (range, 6-150) months. CDDN1 expression was significantly higher in advanced-stage BC cases than in normal breast tissue and limited-stage BC cases. The median overall survival (OS) was 96 months (CI 95%: 67.74-117.59) in the H-CDDN1 group, compared to the L-CDDN1 group not reached, but there was no relation (p>0.05). CDDN1 overexpression was more prominent in low-grade advanced BC cases (p=0.004). The median OS of advanced-stage BC cases with Grade 1 was significantly longer than those with other grades (p=0.04). CONCLUSION: Our results suggest that CDDN1 expression can be used as a potentially appropriate positive prognostic biomarker for advanced-stage BC cases.

Favourable effects of whey protein on acetic acid-induced ulcerative colitis in a rat model.

Introduction: In the present study, we aimed to examine the effects of the administration of whey protein through rectal enema to rats with acetic acid-induced ulcerative colitis on the pathways of nuclear-related factor-2 (Nrf-2), haem oxygenase-1 (HO-1), nuclear factor κB (NF-κB), active protein kinase-1 (AP-1), tumour necrotising factor-α (TNF-α), and cyclooxygenase-2 (COX-2), IL-6, IL-10. Material and methods: Twenty-eight rats were employed for the trial. Ulcerative colitis was induced through the use of acetic acid. The therapeutic doses of whey protein were administered rectally. Ulcerative colitis was subjected to histopathological examination and protein levels in colon tissue were measured with the Western blot method. Results: The significant increases observed in the levels of AP-1, COX-2, IL-6, IL-10, NF-κB, and TNF-α as markers of inflammation following the development of ulcerative colitis showed remarkable decreases along with the administration of whey protein (p < 0.05). On the other hand, we identified a decrease in the Nrf2-ARE signal pathway and HO-1 protein having protective roles in the colon inflammatory response along with the development of ulcerative colitis and activation of the Nrf2-HO-1 pathway by the whey protein. Conclusions: Whey protein modulates Nrf2/HO-1 and NF-kB pathways, thereby creating a therapeutic effect against colonic inflammation induced by acetic acid (AA) due to its anti-inflammatory effects.

Evaluation of the Effects of Systemic Irisin Application on Guided Bone Regeneration in Peri-implant Bone Defects.

This study aimed to investigate the effects of systemic irisin hormone application on new bone formation in peri-implant bone defects. After surgically creating peri-implant bone defects in the metaphyseal part of the tibiae of rats, the rats were randomly divided into 2 equal groups: a control group and an irisin group. In the control group, the rats received no further treatment during the 4-week experimental period after the surgery. The rats in the irisin group, 100 ng/kg irisin was administered intraperitoneally 3 days a week during the 8 weeks experimental period after the surgery. At the end of the experimental period, the rats were euthanized. Implants and surrounding bone tissues were collected for histological new bone formation analysis. The Student t test was used for statistical analysis. There were no significant differences between the groups in the histological analysis, new bone formation and fibrosis (P>0.05). Also, in the irisin group, there was numerically but not statistically more new bone formation detected compared with the controls. Within the limitations of this study, irisin did not affect new bone formation in peri-implant defects, although the numerical values favored the irisin group.

Evaluation of the Effects of Topical Ellagic Acid and Graft Application on Bone Regeneration: an Experimental Study.

Objectives: The aim of this experimental animal study is to investigate the effect of bone graft and topical ellagic acid application on bone regeneration in rats with critical-sized calvarial bone defects. Material and Methods: A total of 24 male Wistar rats were divided into three groups, and 7 mm critical-sized calvarial bone defects were created surgically in them. In the first group, the created defect was left empty, and this acted as a control group. In the second group, only a bone graft was placed in the created defect. In the third group, in addition to placing a bone graft in the created defect, 0.325 mg/kg ellagic acid (EA) was applied topically to the defect. Results: As a result of semiquantitative scoring, osteoblast counts were 2 (SD 0.82) in the control group, 2.71 (SD 0.76) in the graft group, and 1.14 (SD 0.69) in the EA + graft group. The number of osteocytes was 2.29 (SD 0.76) in the control group, 2.71 (SD 1.11) in the graft group, and 1.43 (SD 0.54) in the EA + graft group. When inflammations were evaluated, values of 1.71 (SD 0.75), 1.14 (SD 0.69), and 3 (SD 0.82) were obtained in the control, graft, and EA + graft groups, respectively. Conclusions: Topical ellagic and graft applications show different effects at different doses under topical and systemic conditions. The dose amount of ellagic acid applied, especially in topical applications, has critical importance in bone healing.

Irisin Improves High-Fat Diet-Induced Sexual Dysfunction in Obese Male Rats.

INTRODUCTION: Obesity is known to cause sexual dysfunction including erectile dysfunction and poor semen quality. Lifestyle modifications such as exercise have increasingly been more recognized to lower the likelihood of having sexual dysfunction or infertility in obese men. In this context, as an exercise-mimetic hormone, irisin has a potential to improve obesity-related reproductive dysfunctions. We aimed to elucidate possible effects of irisin on high-fat diet (HFD)-induced reproductive dysfunction in obese male rats. METHODS: Rats were divided into four groups: vehicle, irisin, obese, and obese + irisin. The rats in obese and obese+irisin groups were fed with HFD (60% kcal fat) pellets for 12 weeks to induce obesity, and then obesity-induced sexual dysfunction was confirmed by the sexual behavior test (SBT). Irisin and obese+irisin groups received irisin (100 ng/kg/day) infusion by an s.c. osmotic minipump for 4 weeks after HFD-induced obesity was formed. RESULTS: Irisin did improve a number of measures of copulation, including penile erection, ejaculation, and sexual performance, and also improved sperm morphology and motility and decreased fat-induced testicular damage. It decreased serum leptin levels. On the other hand, irisin did not affect serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone. It also increased gene expression of tyrosine hydroxylase (TH) and adrenoceptor alpha 1A (ADRA1A) in the medial preoptic area (mPOA) and nucleus accumbens (NAc). CONCLUSION: Irisin provided a marked enhancement of HFD-induced decrease in libido, potency, sexual performance, and erection in SBT. Taken together, our results emphasize that irisin has a restorative and improver role in HFD-induced reproductive dysfunctions in obese male rats.

siRNA-mediated stathmin1 silencing inhibits proliferation of prostate carcinoma cell line.

Stathmin1 (STMN1) has been proposed as a possible prognostic marker and a potential therapeutic target for some cancers. We aimed to analyze the changes in autophagy, invasion, apoptosis-related genes in prostate cancer (PCa) cell line (PC-3), after small interfering RNA (siRNA)-mediated STMN1 silencing, and also the relationships of STMN1 expression, clinicopathological parameters, and survival (OS) in PCa cases. The STMN1 expressions were analyzed, immunohistochemically, in formalin-fixed paraffin-embedded 75 PCa and 15 benign prostatic hypertrophy (BPH) tissues. The correlation between the levels of expression STMN1, clinicopathological features, and OS was determined in PCa cases. The siRNA-mediated STMN1 incubated PC-3 cells were transfected and compared to negative control siRNAs. We determined mRNA levels in autophagy, invasion, and apoptosis genes with the combination of reverse transcription-polymerase chain reaction (RT-PCR) and western blotting in PC3 cell lines after STMN1 silencing. It was determined that STMN1 was overexpressed significantly in PCa cases, immunohistochemically. The overexpression of STMN1 was significantly correlated with the high-grade Gleason score, and it was associated with a worse prognosis of PCa cases according to the Kaplan-Meier survival analysis (p < 0.05). Significant silencing in STMN1 was determined (87.5%) after siRNA applications. Especially, invasion genes such as claudin 7, fibroblast growth factor 8, hypoxia-inducible factor 1 subunit alpha, hepatocyte growth factor, matrix metallopeptidase 2, 7 genes, markedly, decreased by siRNA-mediated STMN1silencing. STMN1 silencing was determined to significantly increase caspase 3 protein expression by using western blot analysis (p < 0.001). Although STMN1 silencing did not have a significant effect on the induction of apoptosis and autophagy-related genes in PCa cells, it was shown to affect apoptotic mechanisms through the caps3 protein. siRNA-mediated STMN1 silencing decreases proliferation in the PCa cell line. It is thought that STMN1 can serve as a potential therapeutic target in the advanced stage-PCa, especially.

Evaluation of BMP-2, VEGF, and Vitamin D Receptor Levels in the Ligamentum Flavum of Patients with Lumbar Spinal Stenosis and Disc Herniation.

AIM: To histopathologically evaluate and compare bone morphogenetic protein (BMP)-2, vascular endothelial growth factor (VEGF), and vitamin D receptor (VDR) levels in the ligamentum flavum (LF) of patients with lumbar spinal stenosis (LSS) and lumbar disc herniation (LDH). MATERIAL AND METHODS: Surgical specimens of the LF in 25 patients who underwent surgery for LDH and 25 patients who underwent surgery for LSS were examined histopathologically. The prevalence and severity of BMP-2, VEGF, and VDR immunoreactivity were evaluated to create histoscores (prevalence × severity), which were compared between groups. RESULTS: The mean BMP-2 histoscore was similar in both groups. In the LSS group, the mean VEGF histoscore was significantly higher and the mean VDR histoscore was significantly lower. CONCLUSION: Elevated VEGF and decreased VDR levels in the LF in LSS are associated with more intense inflammation and chronic process of the disease. The prominent expression of BMP-2 in the LF in both diseases suggests that BMP-2 might be affected by inflammation regardless of chronic pressure and degeneration.

Evaluation of the Effects of Topical Application of Chlorhexidine, Ozone, and Metronidazole on Palatal Wound Healing: A Histopathological Study.

ABSTRACT: This study aimed to evaluate the effects of chlorhexidine, metronidazole, and ozone application on the healing of palatal wounds in diabetic rats. A defect in the form of a 4 mm-diameter wound was created on the palatal mucosa of 84 adult female Wistar albino rats, which were randomly divided into 4 groups: control, chlorhexidine, metronidazole, and ozone groups. The animals were euthanized after 3, 6, and 10 days, and wound closure was histologically assessed. On day 3, polymorphonuclear leukocytes were significantly higher in the control group than in the chlorhexidine and ozone groups ( P < 0.05). Fibrosis was higher in the ozone group than in the control and chlorhexidine groups ( P < 0.05). Vascular endothelial growth factor was higher in the metronidazole and ozone groups than in the control group ( P < 0.05). On day 6, the quantity of polymorphonuclear leukocytes was higher in the control, metronidazole, and chlorhexidine groups than in the ozone group ( P < 0.05). Vascular endothelial growth factor was higher in the ozone group than in the control, chlorhexidine, and metronidazole groups ( P < 0.05). On day 10, Vascular endothelial growth factor was higher in the control, chlorhexidine, and metronidazole groups than in the ozone group ( P < 0.05). The authors concluded that the use of chlorhexidine, ozone, and metronidazole pastes resulted in enhanced wound healing, as determined histologically.The authors suggest that ozone supplementation can be an alternative therapy to chlorhexidine in impaired wound healing in diabetes mellitus.

Prognostic Value of TRPM7 Expression and Factor XIIIa-Expressing Tumor-Associated Macrophages in Gastric Cancer.

PURPOSE: TRPM7 is known to play a key role in tumor progression by regulating cellular proliferation, migration, and invasion in various cancer cell lines. However, there are no comprehensive clinical studies about the effect of TRPM7 expression on gastric cancer (GC) prognosis. In this study, it was aimed at investigating the effect of TRPM7 expression on prognosis in GC patients. Additionally, for the first time, it was investigated whether the density of Factor XIIIa-expressing tumor-associated macrophages (TAMs) in GC has an effect on the biological behaviour of the tumor. METHODS: TRPM7 expression and Factor XIIIa-expressing TAM density were immunohistochemically evaluated in paraffin-embedded tumor tissues of 204 GC patients undergoing surgery at a single institution. RESULTS: Tumor size was clearly higher in cases with high TRPM7 expression than those with low expression (p < 0.001, Mann-Whitney U). TRPM7 overexpression was closely related to high depth of tumor invasion (p < 0.001, ANOVA), increased lymph node metastasis (p < 0.001, ANOVA), and high distant metastasis rate (p < 0.001, Mann-Whitney U). These findings exposed that high TRPM7 expression is effective in the progression and aggressiveness of GC. In addition, while high CD8+ TIL density affects the prognosis positively, it was determined that high Factor XIIIa+ TAM density negatively affects the prognosis of patients with GC. Furthermore, multivariate analyses revealed TRPM7 overexpression was independently related with short overall (HR 9.64, 95% CI 5.74-16.19, p < 0.001) and disease-free survival (HR 5.67, 95% CI 3.61-8.92, p < 0.001) in GC patients. CONCLUSIONS: Our data suggest that high TRPM7 expression is closely related to progressive tumor behaviour in GC and independently negatively affects survival in patients. In addition, it was determined that a high density of Factor XIIIa+ TAMs negatively affects the prognosis of patients with GC.

Effects of Systemic Propranolol Application on the New Bone Formation in Periimplant Guided Bone Regeneration.

OBJECTIVES: The aim of this experimental animal study was to evaluate the effects of systemic propranolol on new bone formation in peri-implant bone defects. MATERIAL AND METHODS: Implant slots were created 4mm long and 2.5 mm wide. After the titanium implants were placed in the sockets, 2 mm defects were created in the neck of the implants. Bone grafts were placed in these defects. Then the rats were randomly divided into three equal groups: control (n = 8), propranolol dose-1 (PRP-1) (n = 8), and propranolol dose-2 (PRP-2) (n = 8) groups. In the control group, the rats received no further treatment during the eight-week experimental period after the surgery. The rats in the PRP-1 and PRP-2 groups were given 5 mg/kg and 10 mg/kg propranolol, respectively, every three days for the eight-week experimental period after the surgery. At the end of the experimental period, the rats were euthanized. Blood serum was collected for biochemical analysis, and the implants and surrounding bone tissues were used for the histological analysis. RESULTS: There were no significant differences in the histological analysis results and the biochemical parameters (alkaline phosphatase, calcium, creatinine and phosphorus) of the groups (P > 0.05). Also, in the test groups, there was numerically but not statistically more new bone formation detected compared with the controls. CONCLUSIONS: Within the limitations of this study, propranolol did not affect the new bone formation in peri-implant defects.

The role of endobronchial ultrasound-guided transbronchial needle aspiration in the differential diagnosis of isolated mediastinal and/or hilar lymphadenopathy.

INTRODUCTION: Isolated mediastinal and/or hilar lymphadenopathy (IMHL) has become an increasingly common finding as a result of the increased use of thoracic imaging modalities. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is accepted as the first step diagnostic method in the differential diagnosis of IMHL. OBJECTIVE: To determine the diagnostic yield of the procedure and to analyze clinical and sonographic findings that can be used to differentiate the etiology of lymph node pathologies. METHODS: Patients who underwent EBUS-TBNA procedure between March 2017 and March 2020 were included in this retrospective study. Demographic data, symptoms, comorbid diseases, and EBUS findings were obtained from the records of the patients. RESULTS: EBUS-TBNA provided a diagnosis in 88 patients out of 120 patients (granulomatous diseases n = 54, malignant diseases n = 21, and anthracotic lymph nodes n = 13), and 32 patients had a negative EBUS-TBNA. 22/32 negative EBUS-TBNA samples were true negatives (reactive lymphadenopathy). The sensitivity of the procedure was 89.8% while negative predict value was 68.7%, diagnostic yield of 91.6%. Patients with reactive lymph nodes had significantly more comorbidities (77.3%-19.4%, p < .001) and a lower number of lymph node stations (1.6 ± 0.8-2.7 ± 0.9, p < .001). Patients with anthracotic lymph nodes were older and mostly consisted of females (11/13, p < .001). CONCLUSION: EBUS-TBNA has high-diagnostic efficiency in the differential diagnosis of IMHL. The number and size of lymph node stations can provide useful information for differential diagnosis. Clinical follow-up can be a more beneficial approach in patients with reactive and anthracotic lymph nodes before invasive sampling.