Hepatoprotective actions of melatonin by mainly modulating oxidative status and apoptosis rate in lipopolysaccharide-induced liver damage.

AIM: One of the serious complications of sepsis is liver damage and liver failure. This study aimed to evaluate the protective and therapeutic potential of melatonin in rats with lipopolysaccharide-induced sepsis. MAIN METHODS: Female Spraque-Dawley rats received single a dose of 7.5 mg/kg lipopolysaccharide in saline to create a 24-h sepsis model. One of the other groups received melatonin at a dose of 10 mg/kg/day beginning 1 week before sepsis induction to the end of the experiment. The melatonin group received the same doses of melatonin for the same duration but not lipopolysaccharide. The vehicle group received the same doses of saline, the vehicle of melatonin, for the same duration. Twenty-four hours after the last injection, the rats were decapitated. By appropriate histochemical, immunohistochemical, biochemical, and molecular techniques, anti-necrotic, anti-apoptotic, anti-necroptotic, anti-inflammatory, and antioxidant effects of melatonin were assessed. KEY FINDINGS: Lipopolysaccharide has disrupted liver functions by inducing oxidative stress, inflammation, necrotic, apoptotic, and necroptotic cell death, thus disrupting liver functions. Melatonin was found to be beneficial in terms of inhibiting the intrinsic pathway of apoptosis and tissue oxidant levels, stimulating tissue antioxidant enzyme levels, and restoring hepatocyte functions. SIGNIFICANCE: Melatonin, at those doses and duration, was found to be hepatoprotective by mainly modulating oxidative status and apoptosis rate, however, failed to significantly reduce histopathological damage. We suggest that longer-term melatonin administration may produce anti-inflammatory and anti-necrotic effects as well.

The Inflammatory and Cytological Effect of Repeated Povidone-Iodine Application in Patients Receiving Intravitreal Injections.

OBJECTIVE: To investigate the effect of repeated povidone-iodine (PVI) application on the ocular surface parameters of patients who received intravitreal injections. MATERIALS AND METHODS: In this prospective study, 52 eyes of 52 patients with age-related macular degeneration who underwent unilateral intravitreal injection at least three times in the last 1 year (intravitreal injection [IVI] group), 52 fellow eyes with no previous intravitreal injection (NIVI group), and 51 eyes of 51 healthy subjects (control) were included. Tear break-up time (TBUT), the Schirmer test, the Oxford staining score, the Ocular Surface Disease Index questionnaire, conjunctival impression cytology, and tear inflammatory cytokine levels (interleukin [IL]-1ß and IL-6) were analyzed in all participants. RESULTS: The IVI group had lower TBUT and higher Oxford staining score than the NIVI and control groups ( P <0.05). No significant difference was found between the groups in the Schirmer test ( P =0.161). Conjunctival impression cytology analysis revealed that the IVI group had a significantly lower goblet cell count and significantly higher Nelson staging result than the NIVI and control groups ( P <0.05). As a result of tear cytokine analysis, although IVI and NIVI groups had higher IL-1ß and IL-6 levels than the control group ( P <0.05), there was no difference between NIVI and IVI groups ( P ≥0.05). CONCLUSIONS: Repeated PVI application caused cytotoxic injury to the ocular surface, resulting in goblet cell loss and squamous metaplasia of epithelial cells. As a result, the stability of the tear film layer was found to be impaired and ocular surface-related symptoms developed in patients.

Propolis Enhances 5-Fluorouracil Mediated Antitumor Efficacy and Reduces Side Effects in Colorectal Cancer: An in Vitro and in Vivo Study.

In this study, we investigated the combined treatment of 5-fluorouracil (5-FU) and Anatolian propolis extract (PE) on colorectal cancer (CRC)using in vitro and in vivo studies. We exposed luciferase-transfected (Lovo-Luc CRC) cells and healthy colon cells (CCD-18Co) to varying concentrations of 5-FU and PE to assess their genotoxic, apoptotic, and cytotoxic effects, as well as their intracellular reactive oxygen species (iROS) levels. We also developed a xenograft model in nude mice and evaluated the anti-tumor effects of PE and 5-FU using various methods. Our findings showed that the combination of PE and 5-FU had selectivity against cancer cells, particularly at higher doses, and enhanced the anti-tumor effectiveness of 5-FU against colon CRC. The results suggest that PE can reduce side effects and increase the effectiveness of 5-FU through iROS generation in a dose-dependent manner.

Differential expression of leukemia inhibitory factor and insulin like growth factor-1 between normal pregnancies, partial hydatidiform moles and complete hydatidiform moles.

INTRODUCTION: Leukemia inhibitory factor (LIF) and insulin like growth factor-1 (IGF-1) are two of the most important growth factors mediating trophoblast actions. We hypothesized that the localization and expression patterns of LIF and IGF-1 in partial and complete hydatidiform moles (HM) compared with normal first trimester placentas may provide an understanding of the proliferative processes in HMs. METHODS: The study population included curettage material of women diagnosed as complete or partial HM as a result of histopathological and immunohistochemical examination (complete HM group, n = 8; partial HM group, n = 8) and women undergoing dilatation&curettage for unwanted pregnancies (control group, n = 8). Expression of LIF and IGF-1 among placental cell groups was evaluated immunohistochemically and given a score depending on immunostaining intensity. RESULTS: In normal chorionic villi strong expression of LIF and IGF-1 was present. Both LIF and IGF-1 expressions were weaker in the chorionic villi of complete HMs. In complete mole decidua there was a significant decrease in glandular and endothelial IGF-1 expression along with a decrease in decidual cell LIF expression compared to normal first trimester decidua. LIF expression in extravillous trophoblasts was stronger in complete molar placentas compared to normal placentas. DISCUSSION: LIF and IGF-1 are important regulators of trophoblast proliferation and invasion. Differential expression of LIF and IGF-1 in molar trophoblasts and chorionic villi might have a role in regulation of trophoblasts in complete moles. Decreased expression of glandular IGF-1 and decidual LIF might be related to the decidual changes during trophoblastic proliferation and invasion of decidua in complete HMs.

Histopathological Analysis of Internal Limiting Membrane Surgically Peeled From Eyes with Epiretinal Membrane.

PURPOSE: To investigate histopathological changes of internal limiting membrane (ILM) in patients with epiretinal membrane (ERM) Materials and Methods: Forty-two eyes of 42 patients who were diagnosed as ERM and enrolled for vitreoretinal surgery were included in this study. Brilliant Blue G (BBG) was used to stain the ILM in all patients. ILM was peeled in all subjects and analyzed by light microscopy (methylene blue-Azur II × 40). ILM samples were then fixed in 2.5% glutaraldehyde solution and examined in JEOL-JEM 1400 and 2100F electron microscope and photographed by CCD camera (Gatan Inc., Pleasanton, CA). RESULTS: Remained ERM fragments were observed on 80% of ILM's. Vacuolization of ILM was observed in a patient with diabetic ERM. There were cells and cellular fragments observed mostly at retinal side of ILM which was likely to be a fragment of Muller cells of retina. CONCLUSIONS: Most of the ILM's had residual ERM tissue and contained cells and cellular fragments at retinal side of ILM's. ILM peeling might have a role in decreasing ERM recurrence by removal of residual ERM tissues.

Efficacy of topical mesenchymal stem cell therapy in the treatment of experimental dry eye syndrome model.

Purpose. The current study was set out to address the therapeutic efficacy of topically applied mesenchymal stem cells (MSCs) on dry eye syndrome (DES) induced by benzalkonium chloride (BAC) in rats. Methods. Rats were divided into two groups just after establishment of DES. Eye drops containing either bromodeoxyuridine labeled MSCs (n = 9) or phosphate buffer solution (n = 7) were topically applied once daily for one week. Schirmer test, break-up time score, ocular surface evaluation tests, and corneal inflammatory index scoring tests were applied to all rats at baseline and after treatment. All rats were sacrificed after one week for histological and electron microscopic analysis. Results. Mean aqueous tear volume and tear film stability were significantly increased in rats treated with MSCs (P < 0.05). Infiltration of bromodeoxyuridine labeled MSCs into the meibomian glands and conjunctival epithelium was observed in MSCs treated rats. Increased number of secretory granules and number of goblet cells were observed in MSCs treated rats. Conclusion. Topical application of MSCs could be a safe and effective method for the treatment of DES and could potentially be used for further clinical research studies.