Investigation of fructose consumption on hippocampal insulin and glucagon-like peptide-1 receptors, and metabolic effects in rats.

Objectives: The detrimental effects of high fructose consumption on metabolic health have been extensively studied. However, limited research has focused on the impact of fructose intake on neuroprotective mechanisms, specifically the expression of insulin receptor (INSR) and glucagon-like peptide-1 receptor (GLP-1R) in the hippocampus. Understanding the effects of fructose on these neuroprotective molecules can provide valuable insights into the potential role of fructose in hippocampal dysfunction. The goal of this study is to aim at the basal plasma levels of lipid profile, insulin, GLP-1, and HOMA-IR, as well as the mRNA and protein expression of neuroprotective molecules such as INSR and GLP-1R in Wistar rats fed a high fructose diet. Materials and Methods: Rats were separated into control (C) and high fructose (HF) groups. The HF group was given 20% fructose water to drink for 16 weeks. Results: Fructose ingestion significantly increased abdominal fat (C=1.24±0.08 g, HF=1.79±0.19 g, P<0.05) and plasma triglyceride levels (C=179.22±22.85 µg/ml, HF=242.45±14.45 µg/ml, P<0.05), but had no statistically significant effect on body weight and plasma HDL, LDL, total cholesterol, insulin, and GLP-1 levels (P>0.05). Although INSR mRNA expression in the hippocampus was significantly lower in the HF group compared to the control group (P<0.05), GLP-1R mRNA expression did not differ significantly across the groups (P>0.05). Furthermore, whereas INSR and GLP-1R protein levels in the experimental group were on a declining trend, this trend was not substantially different (P>0.05). Conclusion: These data suggest that fructose consumption may be harmful to the hippocampus by lowering the expression of INSR.

Effect of insulin on IR and GLP1-R expressions in HT22 cells.

Insulin is a significant growth factor that specifically binds to the insulin receptor (IR) in the brain and then activates the PI3K-AKT pathway. Glucagon-like peptide 1 (GLP-1) has a variety of functions including neuroprotection, support for neurogenesis, and increasing insulin signal. This study aims to investigate the effect of insulin administered to immortalized clonal mouse hippocampal cell line (HT22) at different doses and intervals on IR, insulin receptor A (IRA), insulin receptor B (IRB), and Glucagon-like peptide 1 receptor (GLP1-R) mRNA expression and protein levels. The cells were planted in 6 well plates at a density of 3 × 105/4 × 105. Cells treated with insulin at different concentrations (5, 10, and 40 nM) were collected at 0.5, 2, 8, 16, and 24 h. RT-PCR and western blot analysis were used to measure mRNA expression and protein levels. Our results showed that insulin has short and long-term effects on IR and GLP1-R expression depending on dose and time. These findings may guide future studies targeting IR isoforms and GLP1-R in particular, as well as determining the optimal dose and duration of insulin stimulation in insulin signaling research.

The anticancer effects of thymol on HepG2 cell line.

There is an increasing incidence of liver cancer, which is a hazard for global health. The present study was designed to evaluate possible cytotoxic, genotoxic, apoptotic, oxidant and antioxidant effects of thymol on hepatocellular carcinoma (HepG2) cell line. The cytotoxic effect of thymol on HepG2 cell line was determined by XTT test. We also used the HUVEC cell line to show whether thymol damages healthy cells. Oxidative stress level was determined with Total Oxidant Status (TOS) and Total Antioxidant Status (TAS) measurement kits. Apoptosis of cells was detected in flow cytometry with Annexin V apoptosis kit. Apoptotic gene expressions were analyzed by real-time PCR. Genotoxicity was determined by comet assay, which measures DNA damage. The thymol IC50 dose was found to be 11 µM on HepG2 cell line. This dose had no lethal effect on the healthy HUVEC cell line. While thymol significantly decreased the TOS level, it increased the TAS level significantly in HepG2 cells compared to control. Thymol significantly induced apoptosis in HepG2 cells (apoptosis rate in control group 1%, in thymol group 21%). Thymol did not alter the gene expressions of bax, bcl-2, and casp3, all of which are associated with apoptosis. Statistically significant change in favor of genotoxicity was observed in tail length measurements. Our results suggest that thymol decreases oxidative stress in HepG2 cell line, but it induces apoptosis and genotoxicity.

Investigating the Activity of Indole-2-on Derivative Src Kinase Inhibitors Against Chronic Myeloid Leukemia Cells.

BACKGROUND: Src family tyrosine kinases play a potential role in Bcr-Abl-induced leukemogenesis. Src kinase inhibitors are reported as selective inhibitors of chronic myeloid leukemia. OBJECTIVE: Since Src kinase inhibitors have an inhibitive effect on chronic myeloid leukemia, indole derivatives (C-1, C-2, C-3) previously found as potent inhibitors of Src kinase were tested against chronic myeloid leukemia in this study. METHODS: Cell viability of K562 and R/K562 cells, antiproliferative and antioxidant effects, and inhibition profiles of Bcr-Abl kinase of indole derivatives were determined compared to dasatinib and imatinib. RESULTS: The results showed that compounds affected cell proliferation and decreased the levels of Bcr/Abl. These results confirmed that the antileukemic activity of compounds was related to Bcr/Abl expression. Docking studies also presented that compounds are inhibitors of both Src and Abl kinases. Calculation of drug-like properties showed that compounds could be potential drug candidates. CONCLUSION: Among indole-2-on derivatives, previously identified as Src kinase inhibitors, C-2 has been discovered to be a strong anticancer drug that is active against susceptible and resistant K562 cell lines and induces apoptosis.

Elevated serum S100B levels in medication naïve children and adolescents with obsessive-compulsive disorder.

PURPOSE: Obsessive-compulsive disorder (OCD) is a condition characterized by obsessions and/or compulsions. S100B protein is shown to be involved in microglial activation besides intracellular signaling, intercellular communication and cell growth. The relation between S100B protein and various psychiatric disorders except OCD has been studied so far. This study aimed to analyze serum S100B levels for the first time in medication naive OCD diagnosed children and adolescents and to compare them with the control group. MATERIALS AND METHODS: Peripheral blood S100B levels of 27 children and adolescents with OCD were compared to 27 control group subjects to assess any possible association between OCD and S100B levels. All the children and adolescents completed the child version of the Obsessive-Compulsive Inventory (OCI - CV). RESULTS: Compared to control group, higher serum S100B levels were found in OCD group (z = -2.258, p = 0.024). We also found that obsessing and washing subscales' scores and total score of OCI - CV were statistically significantly correlated with S100B levels (respectively, r = .292, p = 0.032; r = .306, p = 0.025; r = .296, p = 0.030). CONCLUSIONS: The present study's findings are in accord with previous studies demonstrating the significance of S100B protein in other psychiatric disorders and suggesting a relation in children and adolescents with OCD for the first time. The role of S100B protein in OCD etiology and pathogenesis should be evaluated further.

Ileal interposition improves metabolic syndrome parameters in a rat model of metabolic syndrome induced by monosodium glutamate.

AIMS: Metabolic syndrome (MetS) is a cluster of metabolic abnormalities. Anatomically restructuring of the gastrointestinal system has recently been an important subject of research in the treatment of MetS and closely related diseases. The aim of this study is to ensure the remission of parameters that define MetS by ileal interposition (IT) and to examine the effect of IT on plasma total GLP-1 and pancreatic GLP-1R expression. MAIN METHODS: To induce MetS, newborn male Wistar albino rats were given MSG (4 g/mg) on days 0, 2, 4, 6, 8, and 10. The control group was injected with saline. In the 5th month, IT or sham surgery was performed on the MetS rats. The lipid levels, abdominal obesity, insulin level, OGTT, Lee index, HOMA-IR, plasma GLP-1 and pancreas GLP-1R expression were evaluated 2 months after surgery. KEY FINDINGS: The results showed that IT significantly improved hyperinsulinemia (p = 0.013) and lipid profile (TG p = 0.0001; TCHOL p = 0.018; HDL p = 0.001). Furthermore, it normalized the Lee index (p = 0.006) and insulin resistance. The IT did not affect the secretion of the GLP-1, but the expression levels of pancreas GLP-1R were increased (p = 0.006). SIGNIFICANCE: IT surgery corrected the MetS parameters in this rat model. The healing effects of IT surgery could be caused by mechanisms in the target tissues of insulin. The decrease in pancreatic GLP-1R levels in the MetS groups might be a compensatory response to the harmful effects of hyperinsulinemia in these groups. These results show that IT can be useful in the treatment of MetS.

Effect of acute and chronic exercise on plasma matrix metalloproteinase and total antioxidant levels.

The relationship between acute and chronic exercise and expression of matrix metalloproteinases (MMPs) in muscles is unknown. There happen some alterations in the oxidant-antioxidant balance due to exercise. This study aimed to investigate the levels of MMP-1, tissue inhibitors of metalloproteinases (TIMP-1), hyaluronic acid (HA), total antioxidant status (TAS), and total oxidant status (TOS) following acute and chronic exercising in rats. Twenty-six Wistar Albino male rats were divided in to three groups: control, acute, and chronic groups. In acute group, treadmill exercise was performed 3 days/wk, 10 min/day for 1 week. In chronic group, exercise performed 7 days/wk, 60 min/day for 4 weeks. At the end of the experiment, plasma MMP-1, TIMP-1, HA, TAS, and TOS levels were measured. In current study, the MMP-1, TIMP-1, HA, and TOS levels not observed statistically significant difference among all groups, but in chronic group, there was a significantly difference (P<0.05) between the control and experimental groups in terms of TAS and oxidative stress index (OSI) levels. TAS, TOS, and OSI levels were significantly different between control and chronic exercise group (P<0.01, P<0.05, and P<0.01, respectively). According to these results, we can say acute and chronic exercise does not effect on plasma MMP-1, TIMP-1, and HA levels.

Examination of levels pentraxin-3, interleukin-6, and C-reactive protein in rat model acute and chronic exercise.

Different types of exercise occurs damage at the cellular level in the muscles. Muscle damage caused by exercise is determined creatine kinase, myoglobin, and increase in levels of acute phase protein and interleukin in blood. The purpose of this study was investigated the levels of pentraxin-3 (PTX-3), interleukin-6 (IL-6), and C-reactive protein (CRP) following acute and chronic exercising in rats. Twenty-six Wistar Albino male rats were divided in to three groups. A treadmill exercise was performed 3 days/week, 10 min/day for 1 week in acute groups. In chronic group, exercise performed 7 days/week, 60 min/day for 4 weeks. At the end of the experiment, plasma PTX-3, IL-6, and CRP levels were measured. In current study, the PTX-3, IL-6, and CRP levels not observed statistically significant difference among control, acute, and chronic groups. The levels IL-6 and CRP were not significantly different between acute and chronic exercise groups (P>0.05). However, the level of PTX-3 was found to be higher in the chronic group compared to the acute group (P<0.05). The PTX-3 level increase on chronic exercise-induced muscle damage. Accorting to our results, we think that PTX-3 may have a protect role on muscle damage during chronic exercises.

Association of Adipokines, Insulin Resistance, Hypertension and Dyslipidemia in Patients with Psoriasis Vulgaris.

BACKGROUND: Systemic inflammation in psoriasis causes insulin resistance and cardiovascular diseases. Adipokines are adipose-tissue-derived factors that are involved in metabolic processes. It is thought that these adipokines are associated with the development of psoriasis. OBJECTIVE: The purpose of this study was to determine the changes in adipokine levels, insulin resistance, hypertension, and dyslipidemia over a 12-week period. METHODS: The study comprised 35 psoriasis patients and 50 controls. Blood samples were obtained twice from the patients, one sample at the start and one at the end of a 12-week follow-up period. The following parameters were assessed in both groups: serum fasting glucose, fasting insulin, homeostasis model assessment-estimated insulin resistance (HOMA-IR) index, serum lipids, adiponectin, leptin, resistin, chemerin, omentin, vaspin, visfatin, retinol-binding protein 4, and high-sensitivity C-reactive protein (hs-CRP) levels; blood pressure; body mass index; and the psoriasis area severity index (PASI) scores. RESULTS: The patients showed an improvement in the PASI score and a significant decrease in serum hs-CRP, omentin, and chemerin values. Moreover, at the start of the follow-up, the psoriasis patients had significantly lower levels of adiponectin and visfatin and significantly higher levels of vaspin and resistin than those of the control group. Visfatin levels correlated negatively with low-density lipoprotein (LDL) and cholesterol, while vaspin and omentin levels correlated positively with diastolic blood pressure. Decreased adiponectin levels correlated negatively with diastolic blood pressure and LDL. CONCLUSION: Plasma levels of adipokines might be useful for evaluating the disease activity of psoriasis and its comorbidities.

Effect of Erythropoietin and Stem Cells on Traumatic Brain Injury.

OBJECTIVE: To investigate the healing effects of erythropoietin (EPO) and stem cells (SCs) in traumatic brain injury (TBI). METHODS: Twenty-nine Wistar albino rats were used and separated into the following groups: control (C), EPO, SC, and SC+EPO. Group C received a TBI only, with no treatment. In the EPO group, 1000 U/kg EPO was given intraperitoneally at 30 minutes after TBI. In SC group, immediately after formation of TBI, 3 × 10,000 CD34(+) stem cells were injected into the affected area. In the SC+EPO group, half an hour after TBI and the injection of stem cells, 1000 U/kg EPO was injected. Before and after injury, trauma coordination performance was measured by the rotarod and inclined plane tests. RESULTS: Seven weeks after trauma, rat brains were examined by radiology and histology. Rotarod performance test did not change remarkably, even after the injury. Compared with group C, the SC+EPO group was found to have significant differences in the inclined plane test results. CONCLUSIONS: Separately given, SCs and EPO have a positive effect on TBI, and our findings suggest that their coadministration is even more powerful.