Toll-like receptor-4 expression and oxidative stress in ocular rosacea.

Purpose: To investigate systemic and ocular toll-like receptor (TLR)-4 expression and its association with oxidative stress markers in ocular rosacea (OR). Methods: This prospective study included 40 patients with rosacea with ocular involvement and 20 healthy volunteers. Tear break-up time (TBUT), Schirmer test, meibomoscore, and ocular surface disease index (OSDI) scores were estimated for all participants. TLR-4 expression in conjunctival epithelium and peripheral blood mononuclear cells was quantified using real-time polymerase chain reaction (RT-PCR). In the tears and serum samples of all participants, antioxidant status (TAS), total oxidant status (TOS), and arylesterase (ARE) activation levels were measured using a fully automated spectrophotometric method, and the oxidative stress index (OSI) was calculated. Results: TLR-4 expression levels and oxidative stress status (TOS and OSI values) were significantly higher (p < 0.01), and antioxidant status (TAS and ARE values) were significantly lower (p < 0.01) in both ocular and blood samples of patients with OR compared with those in controls. A significant positive correlation was found between the ocular and blood values in all parameters (p < 0.05). According to the clinical associations of these results, we found negative correlations between TLR-4, OSI, and TBUT and between TLR-4 and Schirmer, whereas a positive correlation was observed between TLR-4, OSI, and meiboscore and between TLR-4, OSI, and OSDI (p < 0.05). No correlation was found between the OSI and Schirmer results (p = 0.92). Conclusions: TLR-4 and oxidative stress both play important roles in OR pathophysiology and are closely related to clinical findings.

Carbon monoxide (CO) derived from the CO-releasing molecule CORM-2 reduces peritoneal adhesion formation in a rat model.

BACKGROUND: Although low-dose carbon monoxide (CO) administration has been shown to have an anti-fibrotic effect in various fibrotic diseases, its effects on peritoneal adhesion (PA), one of the postoperative complications, are not elucidated. In this study, the effect of CO-releasing tricarbonyldichlororuthenium (II) dimer (CORM-2) administration on the formation of PA and the underlying factors of its potential effect were investigated. METHODS AND RESULTS: After the induction of PA, rats were divided into four groups with 8 rats in each group. The rats received either (i) dimethyl sulfoxide:saline solution (1:10) as a vehicle, (ii) 2.5 mg/kg CORM-2, (iii) 5 mg/kg CORM-2, or (iv) inactive (i) CORM (iCORM) intragastrically every day for a duration of 7 days. PA was not induced in rats (n = 8) designated as sham controls. Gross, histological, immunohistochemical and quantitative real-time polymerase chain reaction analyses were performed to evaluate the effectiveness of CORM-2 administration. Gross analysis showed that CORM-2 administration reduced PA formation compared to rats treated with vehicle. Histological and immunohistochemical examinations showed that increased collagen deposition, myofibroblast accumulation, microvessel density, and M1 macrophage count in the peritoneal fibrosis area of vehicle-treated rats decreased following CORM-2 treatments. PCR analyses showed that CORM-2 treatments decreased hypoxia-induced Hif1a, profibrotic Tgfb1, ECM components Col1a1 and Col3a1, collagen degradation suppressor Timp1, fibrinolysis inhibitor Serpine1, and pro-inflammatory Tnf mRNA expressions, while increasing the M2 macrophage marker Arg1 mRNA expression. CONCLUSIONS: These results suggested that CORM-2 administration reduces PA formation by affecting adhesiogenic processes such as pro-inflammatory response, fibrinolytic system, angiogenesis and fibrogenesis.

Evaluation of Acetic Acid-Induced Chronic Gastric Ulcer Healing by Propionyl-L-Carnitine Administration.

The aim of our study was to investigate the healing effect of propionyl-L-carnitine (PLC) on chronic gastric ulcers and its underlying mechanisms. This study included rats with gastric ulcers induced by applying serosal glacial acetic acid. These rats were then given either saline (vehicle) or PLC at doses of 60 and 120 mg/kg, administered orally 3 days after ulcer induction for 14 consecutive days. Our study found that treatment with PLC resulted in a reduction of the gastric ulcer area, a faster rate of ulcer healing, and stimulated mucosal restoration. Additionally, the treatment with PLC reduced the number of Iba-1+ M1 macrophages while increasing the number of galectin-3+ M2 macrophages, as well as desmin+ microvessels, and α-SMA+ myofibroblasts in the gastric ulcer bed. The mRNA expression of COX-2, eNOS, TGF-ß1, VEGFA, and EGF in the ulcerated gastric mucosa was greater in the PLC-treated groups compared with the vehicle-treated rats. In conclusion, these findings suggest that PLC treatment may accelerate gastric ulcer healing by stimulating mucosal reconstruction, macrophage polarization, angiogenesis, and fibroblast proliferation, as well as fibroblast-myofibroblast transition. This process is associated with the upregulation of TGF-ß1, VEGFA, and EGF, as well as modulation of the cyclooxygenase/nitric oxide synthase systems.

The combination of thymoquinone and paclitaxel shows anti-tumor activity through the interplay with apoptosis network in triple-negative breast cancer.

Thymoquinone (TQ) is the active ingredient of Nigella sativa which has a therapeutic potential in cancer therapy and prevention. In this study, TQ has been shown to induce specific cytotoxicity and apoptosis and to inhibit wound healing in triple-negative breast cancer cell line. TQ also inhibited cancer growth in a mouse tumor model. Moreover, TQ and paclitaxel (Pac) combination inhibited cancer growth in cell culture and in mice. Genes involved in TQ and TQ-Pac-mediated cytotoxicity were studied using focused real-time PCR arrays. After bioinformatic analysis, genes in apoptosis, cytokine, and p53 signaling categories were found to be modulated with a high significance in TQ-treated cells (p < 10(-28), p < 10(-8), and p < 10(-6), respectively). Important to note, TQ has been found to regulate the genes involved in the induction of apoptosis through death receptors (p = 5.5 × 10(-5)). Additionally, tumor suppressor genes such as p21, Brca1, and Hic1 were highly upregulated by TQ and TQ-Pac combination. Interestingly, when cells were treated with high dose TQ, several growth factors such as Vegf and Egf were upregulated and several pro-apoptotic factors such as caspases were downregulated possibly pointing out key pathways manipulated by cancer cells to resist against TQ. In cells treated with the combination of TQ and Pac, genes in apoptosis cascade (p < 10(-12)), p53 signaling (p = 10(-5)), and JAK-STAT signaling (p < 10(-3)) were differentially expressed. TQ has also been shown to induce protein levels of cleaved Caspase-3, Caspase-7, and Caspase-12 and PARP and to reduce phosphorylated p65 and Akt1. The in vivo therapeutic potential of TQ-Pac combination and the genetic network involved in this synergy have been shown for the first time to the best of our knowledge.

Complete Blood Cell Count-Derived Inflammation Biomarkers in Patients with Xanthelasma Palpebrarum.

Objectives: Xanthelasma palpebrarum (XP) is the most common type of cutaneous xanthoma, characterized by yellowish cutaneous plaques commonly located near the medial canthus of the eyelid. Although dyslipidemia significantly contributes to its development, inflammation is also believed to be another element in the pathogenesis, especially in normolipidemic patients. Recently, cell counts derived from complete blood counts have been identified as indicators of systemic inflammatory conditions and have also been under discussion concerning their relevance to ocular diseases. This study aimed to assess inflammation indices derived from complete blood cell counts (CBC) in XP patients with normal lipid levels. Methods: Patients who had been referred to the oculoplasty department with the diagnosis of XP between January 2020 and January 2023 and age-matched control subjects were retrospectively reviewed. Patients who had abnormal lipid profiles and systemic diseases such as diabetes mellitus, hypertension, malignancy, cardiovascular diseases, systemic infections, and inflammatory diseases were not included in the study. CBC parameters were analyzed and compared between the groups. Results: The study comprised 27 normolipidemic patients with XP and 27 age-matched healthy individuals as the control group. There were no statistically significant differences between the two groups in terms of age (p=0.143). The mean hemoglobin, neutrophil, monocyte, lymphocyte, platelet, neutrophil-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, systemic immune-inflammation index, and aggregate index of systemic inflammation values were higher in the patient group, but the differences were not statistically significant (p>0.05). The mean red cell distribution width and platelet-to-lymphocyte ratio appeared to be lower in the patient group compared to the control group; however, no significant differences were observed between the two groups (p=0.272, p=0.387, respectively). Conclusion: This study might offer insights into the pathogenesis of XP, yet numerous questions remain unanswered, awaiting further investigation in future studies.

Investigation of Thiol/Disulfide Homeostasis and Clinical Parameters in Rosacea Patients According to Skin Subtypes.

Background/Objective: The aim of this study was to compare thiol/disulfide homeostasis and clinical parameters of rosacea patients across skin subtypes of the disease and healthy controls. Methods: This prospective study included 90 rosacea patients with different skin subtypes (phymatous, erythematotelangiectatic and papulopustular) and ocular involvement and 30 healthy controls. Plasma native thiol (NT), total thiol (TT) and disulfide levels of the patients and controls were measured using an automated spectrophotometric method, and disulfide/native thiol ratio (DNTR), disulfide/total thiol ratio (DTTR) and native thiol/total thiol ratio (NTTR) were calculated. Tear breakup time (TBUT), meiboscore, Schirmer, ocular surface disease index (OSDI) and rosacea-specific quality of life scale (RosaQoL) were measured clinically. Results: Disulfide, DNTR and DTTR were significantly higher, and NT, TT and NTTR were significantly lower in the rosacea patients compared to the controls (p < 0.001). TBUT and Schirmer were significantly lower, and meiboscore and OSDI were significantly higher in the patients compared to the controls (p < 0.01). According to the skin subtypes, disulfide, DNTR and DTTR were significantly higher, and NTTR was significantly lower in the erythematotelangiectatic subtype compared to the other subtypes (p < 0.002). TBUT was significantly lower, and RosaQol was significantly higher in the erythematotelangiectatic subtype (p < 0.0083). Strong correlations were found between DNTR and TBUT and between DNTR and Meiboscore in all subtypes (p < 0.005), while there were strong correlations between DNTR and OSDI and between DNTR and RosaQol only in the erythematotelangiectatic and papulopustular subtypes (p < 0.05). Conclusions: The thiol/disulfide homeostasis shifted towards disulfides, an indicator of oxidative stress in rosacea, and this was more pronounced in the erythematotelangiectatic subtype. The impairment in TBUT and RosaQol was also more prominent in the erythematotelangiectatic subtype and strongly associated with the DNTR.

Investigation of Choroidal Thickness and Choroidal Vascularity Index in Ocular Rosacea Patients According to Skin Subtypes.

BACKGROUND: To compare the choroidal thickness (CT) and choroidal vascularity index (CVI) values in ocular rosacea (OR) patients across skin subtypes of the disease and healthy controls. METHODS: This prospective study included 90 eyes of 90 mild-moderate OR patients with different skin subtypes (30 phymatous, 30 papulopustular and 30 erythematotelangiectatic) and 30 eyes of 30 age-gender matched healthy volunteers. After obtaining the enhanced depth imaging optical coherence tomography images, the CT was measured at subfoveal, 1500µm nasal and 1500µm temporal to the fovea, and the CVI was calculated using Image J software in the subfoveal, nasal and temporal areas. RESULTS: There was no CT significant difference between OR patients and healthy controls in all regions (p>0.05). CVI values of OR patients were found to be significantly lower in the subfoveal, nasal and temporal regions compared to healthy controls (p=0.02, p=0.01, p=0.01, respectively). No CT difference was detected between the subtypes and healthy controls in all regions (p>0.05). Subfoveal-CVI was significantly lower in the phymatous subtype than the other subtypes and controls (p<0.05), while nasal and temporal-CVI were significantly lower in the phymatous and papulopustular subtypes than the erythematotelangiectatic subtype and controls. CONCLUSION: Our study demonstrated no difference between rosacea skin types and healthy controls in terms of CT. Phymatous and papulopustular subtypes were more likely to be affected by chronic inflammation with having lower CVI in most of the regions. Further studies are needed to investigate the association of inflammatory factors with CVI in OR.

Evaluation of Ocular and Systemic Oxidative Stress Markers in Ocular Rosacea Patients.

Purpose: To investigate oxidative stress markers in tears and serum of patients with ocular rosacea and to examine their association with both ocular surface parameters and cutaneous rosacea subtypes. Methods: This prospective study includes rosacea patients with ocular involvement and healthy controls. We performed ophthalmological examination of all participants and collected tear breakup time (TBUT), Schirmer, Meibomian gland dysfunction (MGD) and Ocular Surface Disease Index (OSDI) scores. We quantified the total antioxidant status (TAS), total oxidant status (TOS), and arylesterase (ARE) levels from tear and serum samples, and calculated the oxidative stress index (OSI). We also classified patients into phymatous, erythematotelangiectatic, papulopustular subtypes. Results: We included 90 ocular rosacea patients and 30 healthy controls. Oxidative stress (TOS, OSI) levels were significantly higher (P < 0.01) and antioxidant levels (TAS, ARE) were significantly lower (P < 0.01) in both tear and serum samples of ocular rosacea patients as compared to controls. We found a significant positive correlation between the tear and serum values regarding oxidative stress parameters (P < 0.05). Besides, OSI was negatively correlated with TBUT and positively correlated with MGD score (meiboscore) and OSDI (P < 0.05). The Schirmer score was not correlated with OSI. No difference was found between the cutaneous subtypes with respect to TAS, TOS, ARE, and OSI results. Conclusions: In this study, we identified oxidative stress markers in the serum and tears of ocular rosacea patients and showed their correlation with clinical signs of MGD, suggesting that oxidative stress contributes to ocular rosacea pathogenesis and that oxidative stress could be an indicator of MGD severity.

High expression level of miR-1260 family in the peripheral blood of patients with ovarian carcinoma.

The most common gynecologic cancers detected in women in Turkey are uterine cancer, ovarian cancer, and cervical cancer. These data reported that a mean of 3800 individuals were diagnosed with uterine cancer, 2790 were diagnosed with ovarian cancer, and 1950 were diagnosed with cervical cancer, and 400 individuals were diagnosed with other gynecologic cancers each year in Turkey. A mean of 14.270 individuals were detected to have been diagnosed with gynecologic cancers each year in the United States of America (USA). Ovarian cancer treatment is generally composed of chemotherapy, and surgery. In general, chemotherapy is administered after surgery. The identification of the molecular pathogenesis of ovarian cancer, and discovery of new moleculer biomarkers which facilitate the ovarian cancer treatment are required for an effective ovarian cancer treatment in clinics. miRNAs are reported to be the possible biologic indicators for various cancer types. We aimed to investigate 2 miRNAs which were suggested to have effect in ovarian cancer in our (previous) monozygotic twin study from miR-1260 microRNA family whose association with ovarian cancer yet has not been reported in the literature. We investigated the expression levels of miR-1260a, and miR-1260b miRNAs, in the peripheral blood lymphocytes of 150 familial and sporadic ovarian cancer patients, and of 100 healthy individuals of the control group who were matched for age, sex, and ethnicity with the patient group, and investigated their possible property of being a biologic indicator for ovarian cancer. The expression results of ovarian cancer patients were evaluated by comparison of the results of the control group in the study. The expression levels of miR-1260a, and miR-1260b in ovarian cancer patients were found highly increased compared with the levels in the control group. miR-1260a expression level in ovarian cancer patients was detected to have increased approximately 17 fold compared with the control group, and miR-1260b expression level in ovarian cancer patients was detected to have increased approximately 33 fold compared with the levels in the control group. The String Analyses showed that the miR-1260a was associated with the ribosomal protein family which was known to be effective in the translation stage of cell and that miR-1260b was associated with CHEK2 protein which was a member of the serine/threonine-protein kinase family. It should be investigated for larger cohorts in benign ovarian diseases and in different stages of patients receiving ovarian cancer treatment whether these two molecules are a noninvasive biomarker and therapeutic target to be used especially in the early diagnosis and prognosis of ovarian cancer in future.