Aim of this study was to investigate the effects of lipoic acid on uterine wound healing by immunohistochemical and biochemical assay in a rat uterine horn model with full thickness injury. Thirty-two female Wistar albino rats were randomised into five groups: Control group, with no intervention; uterine scar group 15days (US15d), uterine scar group 15 days + alpha lipoic acid (ALA) (US15d + ALA), uterine scar group 30 days (US30d) and uterine scar group 30 days + ALA (US30 days + ALA). After uterine incision 100 mg/kg of ALA was administered by oral gavage for either 15 or 30 days. Vascular endothelial growth factor (VEGF) and alpha smooth muscle actin (α-SMA) distribution were evaluated by immunohistochemical methods in tissue and ELISA methods in tissue homogenate. The percentage of α-SMA positive area in US15d + ALA and US30d + ALA groups was significantly higher than US15 and US30d groups. The percentage of VEGF positive area in US15d + ALA group was significantly higher than US15d group and US30d + ALA group was significantly higher than US30d group. Biochemically, α-SMA was significantly higher in the US15d + ALA group when compared to US15d group and higher in US30d + ALA group when compared to US30d group. VEGF was significantly higher in US15d + ALA and US30d + ALA groups when compared to US15 and US30d groups. In conclusion, ALA was found to be effective in enhancing wound healing in uterine full thickness injury.

Background The epigenetic effects of transmission of certain regulatory molecules, such as miRNAs, through maternal milk on future generations, are still unknown and have not been fully understood yet. We hypothesized that breastfeeding regularly by adoptive-mother may cause transmission of miRNAs as epigenetic regulating factors to the infant, and the marriage of milk-siblings may cause various pathologies in the future generations. Results A cross-fostering model using a/a and A vy /a mice had been established. F2 milk-sibling and F2 control groups were obtained from mating of milk-siblings or unrelated mice. Randomized selected animals in the both F2 groups were sacrificed for miRNA expression studies and the remainings were followed for phenotypic changes (coat color, obesity, hyperglycemia, liver pathology, and life span). The lifespan in the F2 milk-sibling group was shorter than the control group (387 vs 590 days, p = 0.011) and they were more obese during the aging period. Histopathological examination of liver tissues revealed abnormal findings in F2 milk-sibling group. In order to understand the epigenetic mechanisms leading to these phenotypic changes, we analyzed miRNA expression differences between offspring of milk-sibling and control matings and focused on the signaling pathways regulating lifespan and metabolism. Bioinformatic analysis demonstrated that differentially expressed miRNAs were associated with pathways regulating metabolism, survival, and cancer development such as the PI3K-Akt, ErbB, mTOR, and MAPK, insulin signaling pathways. We further analyzed the expression patterns of miR-186-5p, miR-141-3p, miR-345-5p, and miR-34c-5p and their candidate target genes Mapk8, Gsk3b, and Ppargc1a in ovarian and liver tissues. Conclusion Our findings support for the first time that the factors modifying the epigenetic mechanisms may be transmitted by breast milk and these epigenetic interactions may be transferred transgenerationally. Results also suggested hereditary epigenetic effects of cross-fostering on future generations and the impact of mother-infant dyad on epigenetic programming.

Objective:The present study was designed to investigate the effects of α-lipoic acid on the abdominal aorta and hypertension in a remnant kidney model histomorphometrically, immunohistochemically, and ultrastructurally.Methods:We surgically reduced the renal tissue mass to 5/6 by applying a remnant kidney model. The rats were divided into 4 groups: Group 1 control group, Group 2- lipoic acid group, Group 3- 5/6 nephrectomy group, and Group IV: 5/6 nephrectomy+lipoic acid-treated group. Lipoic acid solution 100 mg/kg was administered by oral gavage for 8 weeks to Groups II and IV. At the end of the experiment, systemic mean blood pressure was monitored. Then, aortic tissues were removed and fixed. After routine histological procedures, tissue sections were examined histochemically, immunohistochemically (type I angiotensin receptor, vascular endothelial growth factor, alpha-smooth muscle actin), and ultrastructurally.Results:The blood pressure measurements in 5/6 nephrectomy group were significantly higher compared to other groups. In the 5/6 nephrectomy+lipoic acid group, measured blood pressure values and tunica media thickness were significantly lower than in the 5/6 nephrectomy group. In the 5/6 nephrectomy+lipoic acid group, decreased aortic wall thickness, regularity in the structure of elastic fibrils, and more organized elastic lamellae were seen. The expression of type I angiotensin receptor, vascular endothelial growth factor, alpha-smooth muscle actin in the 5/6 nephrectomy+lipoic acid group was decreased compared to the 5/6 nephrectomy group.Conclusion:In the present study, we found that α-lipoic acid could be a favorable agent for the target organ effects of secondary hypertension.

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Alpha-amanitin (α-AMA), the primary toxin of Amanita phalloides, is known to cause nephrotoxicity and hepatotoxicity. Resveratrol is an antioxidant that has shown efficacy in many nephrotoxicity models. The aim of this study was to investigate the effects of resveratrol against the early and late stages of α-AMA-induced nephrotoxicity, compared to those of silibinin, a well-known antidote for poisoning by α-AMA-containing mushrooms. Mice kidney tissues were obtained from five groups: (1) α-AMA + NS (simultaneous administration of α-AMA and normal saline), (2) α-AMA + SR (simultaneous administration of α-AMA and resveratrol), (3) α-AMA + 12R (resveratrol administration 12 h after α-AMA administration), (4) α-AMA + 24R (resveratrol administration 24 h after α-AMA administration), and (5) α-AMA + Sil (simultaneous administration of α-AMA and silibinin). Histomorphological and biochemical analyses were performed to evaluate kidney damage and oxidant–antioxidant status in the kidney. Scores of renal histomorphological damage decreased significantly in the early resveratrol treatment groups (α-AMA + SR and α-AMA + 12R), compared to those in the α-AMA + NS group ( p < 0.05). Catalase levels increased significantly in the α-AMA + SR group, compared to those in the α-AMA + NS group ( p < 0.001). Early resveratrol administration within 12 h after α-AMA ingestion may reverse the effects of α-AMA-induced nephrotoxicity, partly through its antioxidant action, thereby suggesting its potential as a treatment for poisoning by α-AMA-containing mushrooms.

The main goal of the study was to produce chitosan-collagen hydrogel composite scaffolds consisting of 3D printed poly(lactic acid) (PLA) strut and nanofibrous cellulose for meniscus cartilage tissue engineering. For this purpose, first PLA strut containing microchannels was incorporated into cellulose nanofibers and then they were embedded into chitosan-collagen matrix to obtain micro- and nano-sized topographical features for better cellular activities as well as mechanical properties. All the hydrogel composite scaffolds produced by using three different concentrations of genipin (0.1, 0.3, and 0.5%) had an interconnected microporous structure with a swelling ratio of about 400% and water content values between 77 and 83% which is similar to native cartilage extracellular matrix. The compressive strength of all the hydrogel composite scaffolds was found to be similar (∼32 kPa) and suitable for cartilage tissue engineering applications. Besides, the hydrogel composite scaffold comprising 0.3% (w/v) genipin had the highest tan δ value (0.044) at a frequency of 1 Hz which is around the walking frequency of a person. According to the in vitro analysis, this hydrogel composite scaffold did not show any cytotoxic effect on the rabbit mesenchymal stem cells and enabled cells to attach, proliferate and also migrate through the inner area of the scaffold. In conclusion, the produced hydrogel composite scaffold holds great promise for meniscus tissue engineering.

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Objective:This study aimed to assess the effect of new generation oral, direct factor Xa inhibitor rivaroxaban on intimal hyperplasia and smooth muscle cell proliferation at the carotid artery anastomosis site of rabbits.Methods:In total, 14 New Zealand male rabbits weighing 3–3.5 kg were randomized into two groups. Group A (7 rabbits) served as the control group and received no medication. Rivaroxaban was perorally administered to group B (7 rabbits) mg/kg/day for 28 days. Following anesthesia induction, carotid arteries were dissected through a right neck incision. following heparinization at 100 IU/kg, vertical full thickness arteriotomy was performed, then was repaired continuously with 8-0 polypropylene. At day 28, all rabbits were sacrificed and the anastomosed carotid artery segments were analyzed using light microcopy. Hematoxylin–eosin and Masson’s trichrome stained images were analyzed using a digital image analysis program, and lumen diameter, lumen area, intimal and medial thickness, and media areas were measured and results were compared.Results:In the serial sections, the average lumen diameter of group B was higher than that of group A (p=0.001). The lumen areas of group B were also higher than those of group A (p=0.004). The intimal thickness of group B was lower than that of group A (p=0.001). When the section series were evaluated for media thickness, the thickness of group B was lesser than that of group A; the difference was statistically significant (p=0.002).Conclusion:This study may imply a potential midterm benefit of rivaroxaban following arterial anastomosis by reducing intimal proliferation and restenosis.