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Background and Objectives: Hyperglycemia is known to undermine the osteointegration process of implants. In this study, the effects of mangiferin (MF) on the post-implant osteointegration process in a type-II diabetes model were investigated molecularly and morphologically. Materials and Methods: Sprague Dawley male rats were divided into three groups: control, diabetes, and diabetes + MF. All animals were implanted in their tibia bones on day 0. At the end of the 3-month experimental period, the animals' blood and the implant area were isolated. Biochemical measurements were performed on blood samples and micro-CT, qRT-PCR, histological, and immunohistochemical measurements were performed on tibia samples. Results: MF significantly improved the increased glucose, triglyceride-VLDL levels, and liver enzymes due to diabetes. By administering MF to diabetic rats, the osteointegration percentage and bone volume increased while porosity decreased. DKK1 and BMP-2 mRNA expressions and OPN, OCN, and OSN mRNA-protein expressions increased by MF administration in diabetic rats. Additionally, while osteoblast and osteoid surface areas increased with MF, osteoclast and eroded surface areas decreased. Conclusions: The findings of our study indicate that MF will be beneficial to the bone-repairing process and osteointegration, which are impaired by type-II diabetes.

Background and Objectives : PIN1 is overexpressed in several human cancers, including prostate cancer, breast cancer, and oral squamous carcinomas. Juglone (J), derived from walnut, was reported to selectively inhibit PIN1 by modifying its sulfhydryl groups. In this study, the potential effects of juglone, also known as PIN1 inhibitor, on oral cancer and carcinogenesis were investigated at the molecular level. Materials and Methods : 4-Nitroquinoline N-oxide (4-NQO) was used to create an oral cancer model in animals. Wistar rats were divided into five groups: Control, NQO, Juglone, NQO+J, and NQO+J*. The control group received the basal diet and tap water throughout the experiment. The NQO group received 4-NQO for 8 weeks in drinking water only. The Juglone group was administered intraperitoneally in a juglone solution for 10 weeks (1 mg/kg/day). The NQO+J group received 4-NQO in drinking water for 8 weeks, starting 1 week after the cessation of 4-NQO treatment. They were then administered intraperitoneally in a juglone solution for 10 weeks. (1 mg/kg/day). NQO+J* group: received 4 NQO for 8 weeks in drinking water and administered intraperitoneally in a juglone solution for 10 weeks (1 mg/kg/day). They were sacrificed at the end of the 22-week experimental period. The tongue tissues of the rats were isolated after the experiment, morphological changes were investigated by histological examinations, and the molecular apoptotic process was investigated by rt-qPCR and western blot. Results : Histological results indicate that tumors are formed in the tongue tissue with 4-NQO, and juglone treatment largely corrects the epithelial changes that developed with 4-NQO. It has been determined that apoptotic factors p53, Bax, and caspases are induced by the effect of juglone, while antiapoptotic factors such as Bcl-2 are suppressed. However, it was observed that the positive effects were more pronounced in rats given juglone together with 4-NQO. Conclusions : The use of PIN1 inhibitors such as juglone in place of existing therapeutic approaches might be a promising and novel approach to the preservation and treatment of oral cancer and carcinogenesis. However, further research is required to investigate the practical application of such inhibitors.

Background and Objectives: Immune thrombocytopenia (ITP) is an autoimmune disease characterized by the autoantibody-mediated destruction of platelets. The treatment of ITP aims to maintain a sufficient platelet count to prevent bleeding. First-line treatment options include corticosteroids and intravenous immunoglobulin (IVIg), while second-line treatments include splenectomy, rituximab and other immunosuppressive agents, and thrombopoietin (TPO) receptor agonists. This study aims to discuss the treatment methods and results from 100 patients with ITP at the Muğla Training and Research Hospital through a pharmacological approach. Materials and Methods: Demographic characteristics, clinical findings, bone marrow aspiration and biopsy results, and treatments and treatment responses at the time of diagnosis of the 100 patients with ITP who were treated and followed up in the period 2015-2023 were evaluated retrospectively. Results: In the third month after treatment, the overall response percentage was 100% in patients who received steroids only and 88% in patients who received IVIg treatment alone or in combination with steroids ( p > 0.05). The most preferred second-line treatments were splenectomy (41%), eltrombopag (26%), and rituximab (10%). Bone marrow biopsy was performed in 54% of patients, where 35.1% showed increased megakaryocytes, 44.4% adequate megakaryocytes, and 14.8% decreased megakaryocytes. It is noted that eltrombopag and rituximab, in particular, yield higher complete remission rates than immunosuppressive drugs. Conclusions: Considering the side effects of immunosuppressive medications, IVIg, splenectomy, and steroid therapy, the use of new agents such as eltrombopag, which are easily tolerated and have a lower risk of side effects, is expected to increase.

Background and Objectives: The excess consumption of fructose in the diet may cause metabolic syndrome, which is associated with an increased risk of kidney disease. There is limited data on probiotic treatment in high-fructose-induced metabolic syndrome. The present study aims to investigate whether the supplementation of Lactobacillus plantarum (L. plantarum) and Lactobacillus helveticus ( L. helveticus) could provide an improving effect on the renal insulin signaling effectors, inflammatory parameters, and glucose transporters in fructose-fed rats. Materials and Methods: The model of metabolic syndrome in male Wistar rats was produced by fructose, which was given as 20% solution in drinking water for 15 weeks. L. plantarum and L. helveticus supplementations were given by gastric gavage from 10 to 15 weeks of age. Results: High-fructose consumption in rats reduced renal protein expressions of insulin receptor substrate (IRS)-1, protein kinase B (AKT), and endothelial nitric oxide synthase (eNOS), which were improved by L. plantarum and partially by L. helveticus supplementations. Dietary fructose-induced elevations in renal tissue levels of tumor necrosis factor α (TNF-α), interleukin (IL)-1β, IL-6, and IL-10, as well as expression of IL-6 mRNA, were attenuated, especially in L. plantarum treated rats. The increased renal expression of sodium-glucose cotransporter-2 (SGLT2), but not that of glucose transporter type-5 (GLUT5), was suppressed by the treatment with L. plantarum . Conclusion: Suppression in insulin signaling pathway together with the induction of inflammatory markers and upregulation of SGLT2 in fructose-fed rats were improved by L. plantarum supplementation. These findings may offer a new approach to the management of renal dysregulation induced by dietary high-fructose.

Background and objectives: Diabetes mellitus is a disease of insulin deficiency or its inability of usage by the target tissues leading to impairment of carbohydrate, lipid, and protein metabolisms. Resveratrol, having robust anti-inflammatory and anti-oxidant properties, has a high potential to treat or prevent the pathogenesis of diseases. This study was conducted to reveal the relationship between diabetes-induced oxidative stress and tissue inflammation with changes in main enzymatic antioxidants ( cat, sod, gpx, and gst ) and the components of the insulin signaling pathway ( insulin Rβ, irs -1, pi3k, akt , mtor ) in kidney tissues. Additionally, the effects of resveratrol on these parameters were evaluated. Materials and Methods: Male Wistar rats were randomly divided into four groups; (1) control/vehicle; (2) control/20 mg/kg resveratrol; (3) diabetic/vehicle; (4) diabetic/20 mg/kg resveratrol. Gene and protein expressions of antioxidant enzymes and insulin signaling elements were evaluated in renal tissues. Results: Downregulation of antioxidant enzymes' gene expression in the kidney tissues of diabetic rats was demonstrated and this situation was devoted partially to the reduced gene expression of nf κ b . Moreover, the components of renal insulin signaling elements were upregulated at both gene and protein expression levels in diabetic rats, and resveratrol treatment decreased this sensitization towards the control state. Conclusion: Resveratrol partially improved diabetes-induced renal oxidative stress and inflammation due to healing action on renal antioxidant enzymes and insulin signaling pathway components., Competing Interests: The authors declare that there is no conflict of interest associated with this work.