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.

Systemic effect of calcium silicate-based cements with different radiopacifiers-histopathological analysis in rats.

Aim: This in vivo study aimed to examine the systemic effects of contemporary calcium silicate cements (CSC) contain different radiopacifiers in rats. Materials & Methods: Polyethylene tubes filled with BIOfactor MTA (BIO), Neo MTA Plus (NEO), MTA Repair HP (REP), Biodentine (DENT) and empty tubes (control group) were implanted into the subcutaneous tissues of 80 male Spraque Dawley rats for 7 and 30 days (n = 8). After 7 and 30 day, samples of liver and kidney tissues were submitted to histopathological analysis. Blood samples were collected to evaluate changes in hepatic and renal functions of rats. Wilcoxon and post hoc Dunn Bonferroni tests were used to compare between the 7th and 30th days in order to evaluate the histopathological data. Paired-sample t-test was used to compare laboratory values between the 7th and 30th days, ANOVA analysis and a post hoc Tukey test were used to compare values between groups (p < 0.05). Results: On the 7th day, REP, BIO and NEO groups were statistically similar in kidney tissue and the degree of inflammation was found to be significantly higher in these groups compared to the control and DENT groups. On the 30th day, the degree of inflammation of the REP and NEO groups in the kidney tissue was found to be significantly higher than the control, BIO and DENT groups. Although the inflammation in the liver was moderate and mild on the 7th and 30th days, no statistically significant difference was observed between the groups. Vascular congestion was evaluated as mild and moderate in kidney and liver in all groups, and no statistically significant difference was observed between the groups. While there was no statistically significant difference between the groups in the 7th day AST, ALT and urea values, when the creatinine values were compared, the DENT and NEO groups were found to be statistically similar and significantly lower than the control group. On the 30th day, ALT values were statistically similar between the groups. The AST values of the BIO group were found to be significantly higher than the DENT group. While BIO, DENT, NEO and control groups had statistically similar urea values, the REP group was found to be significantly higher than the other groups. The creatinine value of the REP group was significantly higher than the groups other than the control group (p < 0.05). Conclusion: CSCs with different radiopacifiers had similar and acceptable effects on the histological examination of the kidneys and liver systemically, and serum ALT, AST, urea, creatinine levels.

Sodium pentaborate pentahydrate promotes hair growth through the Wnt/ß-catenin pathway and growth factors.

BACKGROUND: Boron (B) is an element involved in many physiological processes in humans and accelerates wound healing and increases angiogenesis. This study aimed to evaluate the possible effects of sodium pentaborate pentahydrate (NaB) on hair growth and reveal its effects on Wnt-1, ß-catenin, vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and transforming growth factor-ß1 (TGF-ß1) signaling pathways, which are important molecular mechanisms involved in hair growth. METHODS: Thirty-five Sprague-Dawley/Wistar albino rats were randomly divided into five groups: non-shaved control, shaved control, NaB 1 mg (shaved + NaB 1 mg elemental B/kg CA), NaB 2 mg (shaved + NaB 2 mg elemental B/kg CA), and NaB 4 mg (shaved + NaB 4 mg elemental B/kg CA). Hair density was measured using the trichoscopy method. Dorsal skin samples were examined histopathologically at the end of the 42nd day, and follicle count, follicle diameter, and subcutaneous tissue thickness were recorded. Wnt-1, ß-catenin, PDGF, VEGF, TGF-ß1, and collagen I levels were analyzed with the Western blot method. RESULTS: In trichoscopy measurements, hair density increased in the NaB 4 mg group (90.9%). In histopathological examination, anagen follicles were observed to increase in the NaB 1 mg and 2 mg groups (p < 0.05). Follicle diameter increased in all NaB groups (p < 0.05). The Wnt-1, ß-catenin, PDGF, VEGF, TGF-ß1, and collagen I level increased in the NaB 1 mg and 2 mg groups (p < 0.05), but they were similar in the NaB 4 mg group compared to the control groups (p > 0.05). CONCLUSION: NaB 1 and 2 mg B/kg supplementation induces the anagen phase in rats via Wnt-1, ß-catenin, VEGF, PDGF, and TGF-ß1 signaling pathways. NaB 4 mg B/kg suppresses these pathways and adversely affects hair growth.

A Case Report of Primary Malignant Pulmonary Melanoma.

We operated on primary malignant melanoma of the lung, attaching the pericardium, diaphragm, and parietal pleura. A 48-year-old female was admitted to our hospital because of persistent dyspnea and cough. A preoperative computed tomography of the chest revealed 3 lesions in the right lung and a mass on the diaphragm between the right lung's lower lobe and heart. A middle lobectomy was performed. The mass on the diaphragm had invaded the diaphragm and pericardium strictly. With a pericardiectomy and a diaphragmatic resection, the mass was removed in an en-bloc manner. Adjuvant chemotherapy was started 1 month after surgery and consisted of 5 days course of iv injection of cisplatin (90 mg/kg). The follow-up period was 5 years and uneventful. For primary pulmonary melanoma, even if it has intrapulmonary metastases, surgery and adjuvant chemotherapy can provide uneventful survival for more than 5 years.

Two Novel Biomarker Candidates for Differentiating Basal Cell Carcinoma from Trichoblastoma; Asprosin and Meteorine Like Peptide.

INTRODUCTION: BCC (Basal Cell Carcinoma) and trichoblastoma are skin tumors originating from the hair follicle. BCC is the most common non-melanoma skin cancer. Differential diagnosis of BCC from trichoblastoma, which is a common benign tumor in terms of histology, morphology, and immunohistochemistry, is not possible. The effects of adipokines on tumorigenesis have attracted attention. MATERIALS AND METHODS: By examining the effects of Asprosin and Meteorine like peptide (METRNL) on these tumors, it is aimed to reach new information in the differential diagnosis of BCC and trichoblastoma. Twenty normal healthy tissue, 17 basal cell carcinoma and 12 trichoblastoma samples were included in the study. RESULTS: Increased expression of Asprosin and METRNL was observed in tumor and stromal tissues in BCC. Although overexpression of METRNL was observed in the lesion area in trichoblastoma, no increase in Asprosin expression was observed. Asprosin and METRNL immunoreactivity were found to be statistically significantly higher in BCC samples compared to control and trichoblastoma. CONCLUSION: Asprosin and METRNL can be used in the diagnosis of BCC. METRNL can be used in the diagnosis of trichoblastoma. These biomarkers are helpful for differentiation between BCC and trichoblastoma.

The effects of intrauterine device on cervico-vaginal smears with liquid-based cytology technique: A North-Eastern Anatolia region study in Turkey.

Intrauterine device (IUD), is one of the most efficient methods of contraception. The aim of study to investigate the effects of intrauterine device in cervicovaginal smears with liquid based cytology technique in our patient population. Cervicovaginal smears of 5492 patients who sought the services of the pathology department in a sixmonth period were reviewed retrospectively. Samples were prepared with liquid based cytology technique. The patients using IUD as contraceptive method (n= 562 cases) were included in the study. The samples taken with the conventional method were excluded from the study. The results were categorized according to the Bethesda system. The age range of the patients was 18-61 years (mean age: 34.6). The most common diagnosis was "negative for intraepithelial lesion or malignancy" (97.2%). In 307 patients (54.6%) there were infection and only in 93 out of them (30.2%) a specific agent was detected. Actinomyces (11%) were recorded as the most common infectious agent, followed by Gardnerella vaginalis (2.8%) and Candida species (2.4%). There were reactive changes in 134 cases (23.8%). In 13 cases (2.3%) epithelial cell abnormalities were detected. The most common cytopathologic diagnosis was ASC-US (atypical squamous cells of undetermined significance) in patients who had epithelial cell abnormalities (2.1%). In conclusion, IUDs increase the frequency of genital infection by disrupting the genital flora. In our study the most frequent agent was Actinomyces, and this rate was higher than some studies. This high rate for Actinomyces may be associated with IUDs that are frequently used for contraception in Erzurum province with long term uses.

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.

Does the cardiovascular drug levosimendan prevent iodinated contrast medium nephrotoxicity with glycerol aggravation in rats?

BACKGROUND: We investigated whether levosimendan prevents contrast medium nephrotoxicity with glycerol aggravation in rats. METHODS: Forty-eight Wistar albino rats were assigned to eight groups (n = 6 × 8). No medication was administered to group I (controls); glycerol (intramuscular injection of 25% glycerol, 10 mL/kg) group II; intravenous iohexol 10 mL/kg to group III; glycerol and iohexol to group IV; iohexol and intraperitoneal levosimendan 0.25 mg/kg to group V; glycerol, iohexol, and levosimendan 0.25 mg/kg to group VI; iohexol and levosimendan 0.5 mg/kg to group VII; and glycerol, iohexol, and levosimendan 0.5 mg/kg to group VIII. One-day water withdrawal and glycerol injection prompted renal damage; iohexol encouraged nephrotoxicity; levosimendan was administered 30 min after glycerol injection and continued on days 2, 3, and 4. The experiment was completed on day 5. Serum blood urea nitrogen (BUN) and creatinine levels, superoxide dismutase (SOD) activity, glutathione (GSH), malondialdehyde (MDA) levels, tumour necrosis factor-α (TNF-α), nuclear factor kappa ß (NFK-ß), interleukin 6 (IL-6), and histopathological marks were assessed. One-way analysis of variance and Duncan's multiple comparison tests were used. RESULTS: Levosimendan changed serum BUN (p = 0.012) and creatinine (p = 0.018), SOD (p = 0.026), GSH (p = 0.012), and MDA (p = 0.011). Levosimendan significantly downregulated TNF-α (p = 0.022), NFK-ß (p = 0.008), and IL-6 (p = 0.033). Histopathological marks of hyaline and haemorrhagic cast were improved in levosimendan-injected groups. CONCLUSION: Levosimendan showed nephroprotective properties due to its vasodilator, oxidative distress decreasing and inflammatory cytokine preventing belongings.

Does daily fasting shielding kidney on hyperglycemia-related inflammatory cytokine via TNF-α, NLRP3, TGF-ß1 and VCAM-1 mRNA expression.

This study aimed to investigate the effects of blood glucose control and the kidneys' functions, depending on fasting, in the streptozotocin-induced diabetes model in rats via TNF-α, NLRP-3, TGF-ß1 and VCAM-1 mRNA expression in the present study. 32 Wistar albino rats were allocated randomly into four main groups; H (Healthy, n = 6), HF (Healthy fasting, n = 6), D (Diabetes, n = 10), DF (Diabetes and fasting, n = 10). Blood glucose and HbA1c levels significantly increased in the D group compared to the healthy ones (p < 0.05). However, the fasting period significantly improved blood glucose and HbA1c levels 14 days after STZ induced diabetes in rats compared to the D group. Similar findings we obtained for serum (BUN-creatinine) and urine samples (creatinine and urea levels). STZ induced high glucose levels significantly up-regulated TNF-α, NLRP-3, TGF-ß1 and VCAM-1 mRNA expression and fasting significantly decreased these parameters when compared to diabetic rats. Histopathological staining also demonstrated the protective effects of fasting on diabetic kidney tissue. In conclusion, intermittent fasting regulated blood glucose level as well as decreasing harmful effects of diabetes on kidney tissue. The fasting period significantly decreased the hyperglycemia-related inflammatory cytokine damage on kidneys and also reduced apoptosis in favor of living organisms.

Protective effect of filgotinib in rat endotoxin-induced uveitis model.

PURPOSE: To investigate the protective effect of filgotinib in endotoxin-induced uveitis model in rats. MATERIALS AND METHOD: This study used 24 Wistar Albino rats. Group I (control group) included the healthy controls; in Group II (sham group), only 300 µg/kg intraperitoneal (ip) lipopolysaccharide (LPS) was administered; and in Group III (treatment group), 3 mg/kg/day filgotinib was administered orally for 10 days followed by 300 µg/kg ip LPS. In all groups, clinical activity scores were evaluated after 24 h. Moreover, histopathological and immunological examinations were performed. RESULTS: In Groups I, II, and III, the mean clinical activity and histopathological examination scores were 0.00, 3.25 ± 0.70, and 1.89 ± 0.60 and 0.00, 2.88 ± 1.12, and 1.44 ± 0.52, respectively. The clinical activity and histopathological examination scores were significantly increased in the sham group compared to the control group (p < 0.05); these findings were significantly reduced in the treatment group (p < 0.05). The mean TNF-α and IL-6 ELISA levels in all groups were 50.20 ± 3.24, 59.87 ± 2.98, and 54.34 ± 4.62 and 30.88 ± 1.79, 36.77 ± 1.21, and 33.66 ± 1.86, respectively. The TNF-α and IL-6 ELISA levels were significantly decreased in the treatment group compared to the sham group (p < 0.05); there was no significant difference between the treatment group and the control group (p = 0.105, p = 0.067, respectively) CONCLUSION: Filgotinib may be an alternative treatment option in preventing the development of noninfectious uveitis.

The effect of the platelet-rich plasma and ozone therapy on tendon-to-bone healing in the rabbit rotator cuff repair model.

BACKGROUND: The aim of this study is to histologically and biomechanically investigate the effects of local PRP and ozone therapy (O2O3) on tendon-to-bone healing in a rabbit model of the supraspinatus tendon tear. METHODS: Four groups were formed to have seven rabbits in each group: repair, R; repair + PRP, RP; repair + ozone, RO; and repair + PRP + ozone, RPO. The supraspinatus tendon was detached by sharp dissection from the footprint and an acute tear pattern was created. Thereafter, tendon repair was performed with the transosseous technique. In the RP group, PRP, and in the RPO group, PRP + O2O3 mixture was injected to the tendon repair site. In the RO group, O2O3 gas mixture was injected into subacromial space three times a week for a total of 4 weeks. The study was ended at postoperative 6th week. RESULTS: When compared with the R group, a statistically significant increase was observed in the biomechanical strength of the RP and RPO groups. The highest increase in biomechanical strength was detected in the RPO group. The histology of the RO and RPO groups showed better collagen fiber continuity and orientation than the R and RP groups. CONCLUSIONS: The results obtained from this study show that the ozonized PRP can be used as biological support to increase tendon-to-bone healing. However, these results need to be supported by clinical studies.

Protective effect of luteolin on acute lung injury in a rat model of sepsis.

We investigated the effects of luteolin (LUT) treatment on acute lung injury caused by cecal ligation and puncture (CLP) induced septic rats. We also investigated the relation between LUT and the cytokines, interleukin-10 (IL-10) and tumor necrosis factor-α (TNF-α). LUT was administered 1 h after CLP surgery. Administration of LUT reduced the glutathione level and superoxide dismutase activity in rat lung tissues. We also found significant reduction of malondialdehyde following LUT treatment. LUT administration also reduced TNF-α and IL-10 mRNA expression in lung tissue. Histopathologic investigation of lung tissue supported our biochemical and molecular findings. Administration of LUT ameliorated lung injury in CLP induced septic rats owing to its antioxidant and anti-inflammatory properties.

LP44 (4-[2-(methylthio)phenyl]-N-(1,2,3,4-tetrahydronaphthalen-1-yl)-1-piperazinehexanamide) exerts anti-ulcer effects via 5-hydroxytryptamine receptor 7 activation on indomethacin-induced gastric ulcers in rats.

AIM: This study aimed to demonstrate the role of serotonin 7 receptor (5-HT7) and the effects of 5-HT7 agonists and antagonists in an indomethacin-induced gastric ulcer. MATERIAL AND METHOD: Male albino Wistar rats (n = 60) were used in the experiments. LP44 (5-HT7 agonist) and SB269970 (5-HT7 antagonist) were administered at 10 mg/kg as a pre-treatment. One hour after the drug treatments, 25 mg/kg of indomethacin (INDO) was administered to all groups except the healthy control group. Six hours after indomethacin administration, all the rats were euthanized. RESULTS: We analyzed the iNOS, eNOS, and 5-HT7 receptor mRNA levels in the stomach tissue of rats by real-time PCR. 5-HT7 mRNA expression was increased in the INDO group compared to the healthy group. LP44 administration exerted a significant upregulatory effect on eNOS mRNA expression and downregulatory effects on iNOS and 5-HT7 mRNA expression compared to the INDO group. However, antagonist (SB269970) administration did not result in such difference in gene expression, but even partially decreased the agonist's effect in combination. Famotidine and agonist exerted similar effects. Histopathological findings supported the beneficial effects of 5-HT7 agonist on gastric tissue. CONCLUSION: The study suggested that activation of 5-HT7 receptor showed a significant anti-ulcerogenic effect in the indomethacin-induced gastric ulcer model.

A promising independent prognostic biomarker in colorectal cancer: P2X7 receptor.

The P2X7 receptor (P2X7R) is an exclusive member of the purinergic receptor family that plays a key role in tumor progression, including colorectal cancer (CRC). P2X7R supports the tumor cells to resist unfavorable conditions by stimulating GLUT-1 expression. GLUT1 is the major glucose transporter in CRC cells and is indicated to be a poor prognostic indicator in patients with CRC. Recently, P2X7R and GLUT-1 are being investigated as prognostic biomarkers in the development of new treatment options. In this study, we aimed to investigate the prognostic value of P2X7R and GLUT-1 expression in CRC. We examined P2X7R and GLUT-1 expression in specimens of 196 CRC patients, immunohistochemically. P2X7R expression was higher in patients with poorly differentiated tumors than in those with well differentiated ones (P = 0.001). P2X7R and GLUT-1 overexpression were correlated to TILs (P<0.001; P = 0.028, respectively), depth of invasion (P<0.001; P = 014, repectively), distant metastasis (P<0.001), and advanced TNM stage (P<0.001). Moreover, multivariate Cox regression analysis showed that P2X7R overexpression clearly correlated with worsened overall survival (HR 4.69; 95% CI 1.77-12.41; P = 0.002). Similarly, patients with GLUT-1 overexpression showed shorter overall and disease-free survival than those with low expression. Our data support that P2X7R and GLUT-1 may be used as an independent prognostic markers and may present new options in terms of targeted therapies for CRC patients.

P2X7 receptor as an independent prognostic indicator in gastric cancer.

Gastric cancer (GC) is one of the foremost causes of cancer-related death around the world. The P2X7 receptor (P2X7R), a member of the P2X7R subfamily of P2 receptors, is a unique molecule that has been shown to affect tumor growth and progression as well as various inflammatory processes, including proliferation of T lymphocytes, release of cytokines, and production of free oxygen radicals. P2X7R has been established as a prognostic parameter in some cancers, and recently, it has been investigated in the development of new targeted therapies. In the present study, we aimed to investigate the prognostic value of P2X7R expression in GC. The expression profile of P2X7R was evaluated immunohistochemically in 156 paraffin-embedded human GC specimens. P2X7R expression was higher in patients with lymph node metastasis than in those without (p < 0.001). P2X7R overexpression was closely related with tumor-infiltrating lymphocytes (TILs) (p = 0.001), vascular invasion (p = 0.006), depth of invasion (p < 0.001), distant metastasis (p < 0.001), and advanced tumor, node, metastasis stage (p < 0.001). Moreover, univariate (hazard ratio [HR] 3.98; 95% confidence interval (CI) 1.89-11.82; p < 0.001) and multivariate (HR 2.24; 95% CI 3.53-12.50; p < 0.001) Cox regression analysis showed that upregulated P2X7R expression clearly correlated with worsened overall survival. In summary, our data revealed that P2X7R may serve as a reliable prognostic parameter and promising therapeutic target for GC.

Carvacrol Protects Against Paclitaxel-Induced Retinal and Optic Nerve Cytotoxicity: A Histopathological Study.

OBJECTIVES: Carvacrol (CV) is a phenolic monoterpenoid found in the essential oil of a number of aromatic plants and herbs. The present study was an investigation of the potential protective effect of CV against paclitaxel (PTX)-induced retinal and optic nerve cytotoxicity in rats. METHODS: A total of 18 adult male Wistar albino rats (250-400g) were randomized into 3 equal groups comprising 6 animals each. Group 1 (control group) received intraperitoneal (IP) saline solution (0.5 mL/200 g) weekly for 4 weeks. Group 2 received an IP dose of PTX (5 mg/kg), and Group 3 received CV (25 mg/kg) 30 minutes after an IP dose of PTX (5 mg/kg) weekly for 4 weeks. At the conclusion of the experimental period, the retinal and optic nerve tissues of the subjects were evaluated histopathologically. RESULTS: All of the retinal specimens in Group 1 (control) were histopathologically normal. In Group 2 (PTX), all of the eyes (6/6) revealed increased retinal vascularity and rosette-like structures in the outer nuclear layer, and in Group 3 (PTX-CV), all of the eyes (6/6) demonstrated normal retinal vascularity and the absence of rosette-like structures. All of the optic nerve specimens in Group 1 (control) were histopathologically normal. In Group 2 (PTX), all of the eyes (6/6) demonstrated severe vacuolization and a decreased number of astrocytes and oligodendrocytes in the optic nerve specimens, while 3 eyes (3/6) showed marked single cell necrosis. None of the eyes in Group 3 (PTX-CV) demonstrated either vacuolization or a reduction in the number of astrocytes and oligodendrocytes. No remarkable single cell necrosis was observed in the optic nerve specimens of Group 3 (PTX-CV). CONCLUSION: The histopathological findings indicated that CV played a protective role against PTX-induced cytotoxicity. CV might be a promising resource to counteract oxidative stress-based cytotoxicity in the field of retinal and optic nerve disorders.

Intratumoral Cytotoxic T-Lymphocyte Density and PD-L1 Expression Are Prognostic Biomarkers for Patients with Colorectal Cancer.

Background and objectives: Cytotoxic T-lymphocyte (CTL)-mediated inflammatory response to tumors plays a crucial role in preventing the progression of some cancers. Programmed cell death ligand 1 (PD-L1), a cell-surface glycoprotein, has been reported to repress T-cell-mediated immune responses against tumors. However, the clinical significance of PD-L1 in colorectal cancer (CRC) remains unclear. Our aim was to elucidate the prognostic significance of PD-L1 expression and CD8+ CTL density in CRC. Materials and methods: CD8 and PD-L1 immunostaining was conducted on 157 pathologic specimens from patients with CRC. The CD8+ CTL density and PD-L1 expression within the tumor microenvironment were assessed by immunohistochemistry. Results: Tumor invasion (pT) was significantly correlated with intratumoral (p = 0.011) and peritumoral (p = 0.016) CD8+ CTLs density in the tumor microenvironment. In addition, there was a significant difference in the intensity of CD8+ CTLs between patients with and without distant metastases (intratumoral p = 0.007; peritumoral p = 0.037, T-test). Lymph node metastasis (pN) and TNM stage were significantly correlated with PD-L1 expression in CRC cells (p = 0.015, p = 0.029, respectively). Multivariate analysis revealed a statistically significant relationship between the intratumoral CD8+ CTL density and disease-free survival (DFS) (hazard ratio [HR] 2.06; 95% confidence interval [CI]: 1.01-4.23; p = 0.043). The DFS was considerably shorter in patients with a high expression of PD-L1 in cancer cells than those with a low expression (univariate HR 2.55; 95% CI 1.50-4.34; p = 0.001; multivariate HR 0.48; 95% CI 0.28-0.82; p = 0.007). Conversely, patients with high PD-L1 expression in tumor-infiltrating lymphocytes had a longer DFS in both univariate analysis (HR 0.25; 95% CI: 0.14-0.44; p < 0.001) and multivariate analysis (HR 3.42; 95% CI: 1.95-6.01; p < 0.001). Conclusion: The CD8+ CTL density and PD-L1 expression are prognostic biomarkers for the survival of patients with CRC.

The effects of Beeswax, Olive oil and Butter impregnated bandage on burn wound healing.

BACKGROUND: Beeswax, Olive oil and Butter (BOB) are nutritive products that could support wound healing by adsorption to bandage. This study demonstrated the therapeutic effects of BOB on second degree burn. METHODS: Second degree burn model was created in rats. Experimental groups were assigned to Healthy, Burn, Silver Sulfadiazine (SS) and BOB. The effects of BOB were evaluated on skin regeneration, vesicles and bullae and fibroblast activity by histopathological analyses and wound contraction percent were determined. Transforming Growth Factor-Beta1 (TGF-ß1) and Vascular Endothelial Growth Factor-alpha (VEGF-α) mRNA expressions were analyzed with Real Time-Polymerase Chain Reaction. All parameters analyzed at 3rd, 7th, 14th days. RESULTS: The BOB treatment increased TGF-ß1 and VEGF-α expressions compared to Burn group. The histopathological analyses showed that epidermis and dermis layers injured due to burn. BOB treatment augmented the regeneration of these layers and increased fibroblast activity and keratinization which are play important role on the new blood vessels production. Also with the BOB treatment we showed wound contraction levels were higher than Burn and SS treatment. CONCLUSION: This study demonstrated that beeswax-olive oil-butter mixture impregnated bandage treatment in a second-degree burn rat model improved burn wound healing and encouraged skin renewal via modulating tissue TGF-ß1 and VEGF-α.

Carvone protects against paclitaxel-induced retinal and optic nerve cytotoxicity: a histopathological study.

Purpose: Carvone (CVN) is a natural monoterpene found in essential oils of many aromatic plant species. In this study, we investigated the protective effect of CVN against paclitaxel (PTX)-induced retinal and optic nerve cytotoxicity in rats. Methods: Twenty-four male adult Wistar albino rats (250-400 g) were randomized into four equal groups comprising six animals in each. Group 1 (control group) received intraperitoneal (i.p.) saline solution (0.5 mL/200 g) weekly for 4 weeks. Group 2 received i.p. CVN [(S)-(+)- CVN, (5S)-5-Isopropenyl-2-methyl-2-cyclohexen-1-one, C10H14, 25 mg/kg], while Group 3 received i.p. PTX (5 mg/kg) weekly for 4 weeks. Group 4 received i.p. CVN (25 mg/kg) 30 min after i.p. PTX (5 mg/kg) weekly for 4 weeks. At the end of the experimental period, retinal and optic nerve tissues were evaluated histopathologically. Results: All retinal specimens in control and CVN groups were histopathologically normal. In PTX group all eyes (6/6) demonstrated increased retinal vascularity and rosette-like structures in the outer nuclear layer, while in PTX-CVN group all eyes (6/6) demonstrated normal retinal vascularity and absence of rosette-like structures. All optic nerve specimens in control and CVN groups were histopathologically normal. In PTX group all eyes (6/6) demonstrated severe vacuolization and decrease in the number of astrocytes and oligodendrocytes, while 3 eyes (3/6) demonstrated marked single cell necrosis. In PTX-CVN group, 4 eyes (4/6) demonstrated moderate vacuolization while, 2 eyes (2/6) had none. Compared with PTX group, 1 eye (1/6) in PTX-CVN group demonstrated a decrease in numbers of astrocytes and oligodendrocytes while 5 eyes (5/6) were normal. No remarkable single cell necrosis was observed in PTX-CVN group. Conclusions: Our histopathological findings demonstrated the potential protective role of CVN against PTX-induced retinal and optic nerve cytotoxicity. CVN might be a promising molecule in counteracting oxidative stress-based cytotoxicity in the field of retinal and optic nerve disorders.

A New Neuropathologic Mechanism of Blood pH Irregularities After Neck Trauma: Importance of Carotid Body-Glossopharyngeal Nerve Network Degeneration.

OBJECTIVE: We created a neck trauma model by injecting blood into the sheath of rabbits' carotid bodies (CBs). Then we determined the relationship between neuronal degeneration of the CB due to hemorrhage of this organ and its clinical effects such as blood pH and heart rhythm. METHODS: The present study included 24 adult male New Zealand rabbits. The animals were divided into 3 groups: control (n = 5); sham (0.5 mL saline injected into CBs; n = 5); and study (CB trauma model; n = 14). pH values and heart rhythms were recorded before the experiment to determine the values under normal conditions, and measurements were repeated thrice in the days following the experiment. The number of normal and degenerated neuron density of CBs was counted. The relationship between the blood pH values, heart rhythms, and degenerated neuron densities was analyzed. RESULTS: Heart rhythms were 218 ± 20 in the control group, 197 ± 16 in the sham group (P = 0.09), and 167 ± 13 in the study group (P < 0.0005). pH values were 7.40 ± 0.041 in the control group, 7.321 ± 0.062 in the sham group (P = 0.203), and 7.23 ± 0.02 in study group (P < 0.0005). Degenerated neuron densities were 12 ± 4/mm3 in the control group, 430 ± 74/mm3 in the sham group (P < 0.005), and 7434 ± 810/mm3 in the study group (P < 0.0001). CONCLUSIONS: A high degenerate neuron density in the CB can decrease blood pH and hearth rhythm after neck trauma, and there might be a close relationship between the number of degenerated neurons and clinical findings (such as heart rhythm and blood pH). This relationship suggests that injury to the glossopharyngeal nerve-CB network can cause acidosis by disturbing the breathing-circulating reflex and results in respiratory acidosis.