Inflammation as a Neurobiological Mechanism of Cognitive Impairment in Psychological Stress.

The feeling of emotional tension, restlessness, pressure, and inability to relax is referred to as psychological stress. Although it is unclear how psychological stress affects neurobiological processes, several factors are thought to be involved, including central and peripheral neuroinflammation, structural degeneration in the prefrontal cortex and hippocampus, alterations in fear neurocircuitry, and neuroplasticity. Aside from data relating cognitive impairment to chronic low-grade inflammatory stress, there is growing evidence linking mental stress, oxidative stress, and systemic inflammation to the development of psychological disorders. After chronic and acute illnesses, insomnia, depression, anxiety, posttraumatic stress disorder, and cognitive impairment were reported. Cognitive impairment is exacerbated by systemic and central inflammatory processes. There is uncertainty about the potential mechanisms causing these symptoms, although they are likely complex, with systemic inflammation playing a significant role. Therefore, this review aims to investigate the role of inflammation in stress-induced cognitive impairment. Depicting the inflammatory mechanisms of cognitive impairment is critical for understanding and treating illnesses, such as chronic stress exposure and anxiety disorders.

Mangiferin Induces Post-Implant Osteointegration in Male Diabetic Rats.

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.

Evaluation of the Effect of Different Inhalation Agents on Ovaries with Hyperthermic Intraperitoneal Chemotherapy: An Experimental Study.

Background and Objectives: Cisplatin is a chemotherapeutic drug that is frequently used with hyperthermic intraperitoneal chemotherapy (HIPEC). Cisplatin-induced gonadotoxicity leads to a depletion of the ovarian reserve, causing premature ovarian insufficiency. This study aimed to investigate the impact of hyperthermia on cisplatin-induced ovarian toxicity and to determine whether sevoflurane or desflurane could be a more appropriate choice of anesthetic for reducing ovarian toxicity in HIPEC procedures. Materials and Methods: A total of 24 New Zealand rabbits were randomly divided into 4 groups as follows: Group H: HIPEC (cisplatin 7 mg/kg), Group HS: HIPEC (cisplatin 7 mg/kg) + 3% sevoflurane (2 h), Group HD: HIPEC (cisplatin 7 mg/kg) + 6% desflurane (2 h), and Group C: Control (Saline). Two catheters were placed in the abdominal cavity, the upper and lower quadrants. The perfusate was heated to 42 °C and given intraperitoneally for 90 min at a rate of 4 mL/min by catheters. Ovarian tissues were collected for Hematoxylin and Eosin staining and immunohistochemical analysis. Results: The primary follicle number was significantly decreased in Group H and HD compared to the C group (p < 0.05). Bax expression was high in Group H, according to all groups (p < 0.0001). Bax expression significantly decreased after sevoflurane, compared to group H (p = 0.012). The bcl-2 expression decreased in all groups compared to the C group. Bcl-2 expression was increased with sevoflurane compared to the H group (p = 0.001). Caspase 3 and p53 expression increased in all groups compared to the C group. p53 expression was decreased with sevoflurane and desflurane compared to the H group (p = 0.002, p = 0.008, respectively). Conclusions: The application of cisplatin with the intraoperative HIPEC method caused ovarian damage. According to our results, sevoflurane anesthesia could be a better option in mitigating cell death I the n ovarian reserve (follicle count) and apoptosis in the HIPEC procedures. We think that our findings should be supported by large series of clinical and experimental studies.

Impact of Juglone, a PIN1 Inhibitor, on Oral Carcinogenesis Induced by 4-Nitroquinoline-1-Oxide (4NQO) in Rat Model.

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.

Investigation of the antioxidant effect of Chrysin in an experimental cataract model created in chick embryos.

PURPOSE: Cataract, which occurs as a result of lens opacification, is one of the most common causes of vision loss. In the literature, deterioration of the antioxidant system due to the increase in reactive oxygen species and oxidant levels is shown among the causes of cataract formation. The aim of this study was to investigate the antioxidant effect of chrysin on steroid-induced cataract development in an experimental chick embryo model using morphological, histological and biochemical parameters. METHODS: Within the scope of the study, 150 specific pathogen free (SPF) fertilized eggs were used. Eggs were divided into 6 groups as control (group 1), corn oil (group 2), hydrocortisone hemisuccinate sodium (HC) (group 3), low dose chrysin (group 4), medium dose chrysin (group 5) and high dose chrysin (group 6). On the 15th day of incubation, Chrysin and HC were applicated to the air sac of the eggs with Hamilton and/or insulin injector. On day 17, the chick embryos were removed from the eggs and the bulbus oculi of the embryos were dissected. Lenses of 9 embryos were used for morpholigical cataract grading in each group, lens of 8 embryos for biochemical analysis and intact eyes of 7 embryos for histological evaluation (TUNEL method). RESULTS: No opacity was observed in any of the lenses in Group 1 and 2. Cataract was observed in all lenses in Group 3. The mean opacity grades in group 3 were statistically significantly higher when compared to group 1 and 2 (p<0.05). The difference between group 6 and group 3 was statistically significant (p<0.05). GSH and TAS levels in the lenses were statistically significantly decreased compared to the control group due to HC application (p<0.05). It was determined that the decreased GSH and TAS levels in the lenses increased in relation to the Chrysin application doses. The increased levels of MDA, TOS, caspase 3 and caspase 9 in the HC group decreased significantly depending to the chrysin doses (p<0.05). In addition, while the rate of apoptotic cells determined by the TUNEL method was statistically significantly higher in the HC administered group than in the control group (p<0.05), it was statistically significantly decreased in the chrysin-administered groups, in relation to the dose of chrysin (p<0.05). CONCLUSIONS: We think that anti-cataract effect of crhysin may be due to the antioxidant and antiapoptotic properties of chrysin. However, more research is needed to clarify the anti-cataract effects of chrysin.

The protective effect of apelin-13 on cardiorenal toxicity induced by cyclophosphamide.

Cyclophosphamide is a chemotherapeutic drug that is widely used in the clinic and can cause multi-organ toxicity. Apelin-13 is an endogenous adipocytokine with antioxidant properties. Therefore, this study investigated the possibility of apelin-13 being a potential therapeutic agent on cardiac toxicity and nephrotoxicity caused by cyclophosphamide. In this study, a total of four groups were formed with eight rats in each group. Group I: the control group was administered only saline (i.p.). Group II: cyclophosphamide, a single dose of 200 mg/kg (i.p.) on day 7. Group III: apelin-13 (15 µg/kg), for 7 days (i.p.). Group IV: administered apelin-13 (15 µg/kg) (i.p.) for 7 days and a single dose of cyclophosphamide (200 mg/kg) (i.p.) on day 7, the rats were sacrificed on day 8. Lactate dehydrogenase, cardiac troponin I (cTnI), creatine kinase MB (CK-MB), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), malondialdehyde, creatinine, and blood urea nitrogen were found to be high in the cyclophosphamide group; however, these values were reduced with apelin-13 administration. Antioxidant enzymes such as superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase, and reduced glutathione (GSH) decreased in the cyclophosphamide group, and apelin-13 increased these enzyme activities. In addition, histopathological examinations also supported the results obtained. The findings of this study showed that apelin-13 has a protective effect against cardiorenal toxicity caused by cyclophosphamide.

Better neuroprotective profile of caffeic acid phenyl ester over resveratrol in non-traumatic ischemia-reperfusion injury of the spinal cord.

BACKGROUND: Spinal cord ischemia has serious sequelae. The aim of this study is to investigate the effects of resveratrol and caffeic acid phenyl ester (CAPE), a propolis derivative, on spinal cord injury induced by ischemia-reperfusion (IR). METHODS: In our research, 30 male Wistar albino rats, 200-250 gr, were used. Before the experiment, during a week of the process, the rats were fed with these two agents, and the experimental group rats were exposed to spinal cord IR injury. At the end of the experiment, spinal cord samples were taken from the sacrificed rats. Bax, p53, nNOS, and Beclin-1 immunoreactivity moreover TUNEL (+) cells were evaluated with immunohistochemically in the IR-induced damaged rats. RESULTS: It has been clearly determined that the TUNEL (+) apoptotic cell number and immunopositive cells of nNOS, Beclin-1, p53, Bax were raised in the IR group. However, these increments partially were restored in the resveratrol and CAPE-fed rats with IR-induced injury. CONCLUSION: In light of our data, resveratrol, and CAPE could be beneficial in spinal cord IR injury. Although both agents provide beneficial effects, it can be said that CAPE is partially more effective in spinal cord injury caused by IR.

High-fructose in drinking water initiates activation of inflammatory cytokines and testicular degeneration in rat.

The increased consumption of high-fructose in diet may contribute to high prevalence of metabolic syndrome in the world. The influence of high-fructose diet on male reproductive system has been poorly documented. In this study, we investigated the effects of dietary high-fructose on the expression of inflammatory cytokines in association with certain testicular proteins and sex hormones in the testis of rats. Fructose was given to the rats as 20% solution (7.8 mg/kg) in drinking water for 15 weeks. Dietary high-fructose caused testicular degeneration, also decreased testicular concentration of testosterone and right testis absolute weight. This dietary intervention increased iNOS and TNF-α mRNAs as well as iNOS, NF-κB, and p-NF-κß proteins, but decreased IL-10 and IL-6 mRNAs expressions, in testicular samples of rats. Moreover, testicular TNF-α, IL-1ß, and iNOS and plasma IL-1ß levels were significantly increased in rats fed with fructose. A marked increase in the expression level of IGF-1R protein was considered in testicular tissue of fructose-treated rats. The expression intensities of c-kit, claudin-1, and pan-cadherin were comparable in seminiferous tubules of control and fructose-treated rats. In conclusion, high-fructose intake of rats leads to activation of inflammatory cytokines, which is accompanied by testicular degeneration. These changes could be responsible for hormonal dysfunction with low intra-testicular testosterone level, which could be relevant to male infertility.

Protective effect of valproic acid on ischemia-reperfusion induced spinal cord injury in a rat model.

PURPOSE: This study aims to determine the anti-inflammatory, antioxidant, and anti-apoptotic effects of valproic acid (VPA) on rat spinal cord tissue in ischemia-reperfusion (IR) injury model created by abdominal aorta occlusion. MATERIALS AND METHODS: Sprague Dawley rat (male sex) weighing 190-260 g divided into four experimental groups: control only underwent laparotomy, sham group, pre-IR injury (200 mg/kg dose), and post-IR injury (300 mg/kg) VPA. We measured serum levels of TNF-α, IL-6, IL-1ß, IL-18, Total Oxidant Status (TOS) and Total Antioxidant Status (TAS), and serum Oxidative Stress Index (OSI) ratio, and tissue expression of Bax and Bcl2, Caspase3, and Bax/Bcl2 ratio. RESULTS: Serum IL-18 was higher in the sham than the control group(P = 0.001), and there were declines in the pre-IR treatment (P = 0.002) and the post-IR treatment when compared to sham (P = 0.001). Despite these reductions, IL-18 expression levels in both the pre- and post-IR treatment groups were higher than in the control group (P = 0.001 & P = 0.003). The favorable effects of pre-IR VPA administration on immunohistochemical biomarkers were superior to post-IR VPA administration. CONCLUSIONS: Comparative analyses between prophylactic VPA administration and post-IR interventions revealed congruence in their anti-inflammatory and anti-apoptotic ramifications. VPA can reduce spinal cord IR injury in an aortic occlusion model of rats.

Sestrin-2 and hypoxia-inducible factor-1 alpha levels in major depressive disorder and its subtypes.

BACKGROUND: The objective of this study is to measure the levels of sestrin-2 (SESN2) and hypoxia-inducible factor-1 alpha (HIF-1α), which can be determinants in the relevant physiopathology and etiology, assessment of the clinical severity, and identification of new treatment targets in major depressive disorder (MDD) and its subtypes. METHODS: A total of 230 volunteers, including 153 patients diagnosed with MDD according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), and 77 healthy controls, were included in the study. Of the MDD patients included in the study, 40 had melancholic features, 40 had anxious distress features, 38 had atypical features, and the remaining 35 had psychotic features. All participants were administered the Beck's Depression Inventory (BDI) and Clinical Global Impressions-Severity (CGI-S) scale. Serum SESN2 and HIF-1α levels of the participants were measured using the enzyme-linked immunosorbent assay (ELISA) method. RESULTS: The HIF-1α and SESN2 values of the patient group were found to be significantly lower than those of the control group (p < 0.05). The HIF-1α and SESN2 values were significantly lower in patients with melancholic, anxious distress, and atypical features compared to the control group (p < 0.05). The HIF-1α and SESN2 levels did not differ significantly between patients with psychotic features and the control group (p > 0.05). CONCLUSION: The findings of the study suggested that knowledge of SESN2 and HIF-1α levels may contribute to the explanation of the etiology of MDD, objective assessment of the severity of the disease, and identification of new treatment targets.

Use of AgNOR staining to determine the effect of metoclopramide on neural tube development in early chick embryos.

Nausea and vomiting during pregnancy are common problems and prolonged pharmacological treatment often is needed; however, the teratogenic effects of anti-emetic drugs on neural tube (NT) development are not clear. We investigated the effects of different doses of metoclopramide on NT development in 48 and 72 h chick embryos using an argyrophilic nucleolar organizing region (AgNOR) staining method. We used 150 fertile, specific pathogen-free eggs incubated for 28 h, then randomly divided into five equal groups: group A, sham control was administered 0.9% saline; groups B - E were administered 0.15 mg/egg, 0.3 mg/egg, 0.6 mg/egg and 1.2 mg/egg, respectively. Half of the eggs in each group were taken from the incubator at 48 h incubation and the other half at 72 h incubation. After incubation, eggs were opened, embryos were dissected from their membranes, fixed with 10% formalin and examined by light microscopy. The NT status, i.e., open or closed, and somite number, crown-rump length, morphological features and gross developmental abnormalities were recorded. Excised embryos were sectioned and stained using hematoxylin and eosin or the AgNOR procedure and examined for morphology and histopathology. Delayed NT closure was observed in all 48 h drug exposed embryos, but in the 72 h groups, this occurred only in high-dose groups. Somite number was reduced significantly in groups C - E compared to the control group. Crown-rump length was decreased in both 48 and 72 h embryos. We found a decreased total AgNOR area:nuclear area ratio in 48 and 72 h embryos of all experimental groups. We found that metoclopramide delayed NT closure in chick embryos in a dose-dependent manner.

How did the psychological impact of COVID-19 change healthcare workers in times of fighting the pandemic?

BACKGROUND: This study is the second leg of a two-leg project. In the first leg, the effect of the COVID-19 pandemic on healthcare workers (HCWs) was investigated in the period between the first case in Turkey and the arrival of the first case in the hospital. OBJECTIVE: In this second leg, three months after the first evaluation, we aimed to investigate whether psychological effects of COVID-19 such as stress, anxiety, depression, and sleep quality have been changed on HCWs. METHODS: This was a 3-month observational study. 169 hospital staff who participated in the first leg of the study were reached and asked to participate in the second leg evaluation in Gaziantep University Medical Faculty Hospital.110 HCWs accepted to participate. Impact of Event Scale (EIS-R), Depression Anxiety Stress Scale (DASS-21), and Pittsburgh Sleep Quality Index (PSQI) were used to assess in both two legs. Paired Sample T-test was used for comparison of normally distributed variables. Wilcoxon test was used for the comparison of abnormally distributed variables. SPSS 22.0 software was used in the analysis of variables. RESULTS: Of the HCWs with an average age of 33.9±6.6 years, 59% (65) were males. There was no significant difference between the two legs in terms of IES-R, DASS-21, and PSQI scales. CONCLUSION: This study suggests that the psychological effects of the COVID-19 pandemic on HCWs started with the pandemic, before the arrival of the first case in the hospital. Also, these psychological effects continued similarly without significant change after the initiation of direct contact with COVID-19 patients and even after the increase in COVID-19 patients in a hospital which in they work.

Masseter muscle and gingival tissue inflammatory response following treatment with high-fructose corn syrup in rats: Anti-inflammatory and antioxidant effects of kefir.

The aim of the study was to evaluate whether high-fructose corn syrup (HFCS) intake (20% beverages) impacts antioxidative structures and inflammation in the gingival tissue and masseter muscle of rats. Kefir was tested for its potential utility on changes induced by HFCS. Animals were randomly divided into four groups as control, kefir, HFCS, and HFCS plus kefir. HFCS was given as 20% solutions in drinking water while kefir supplementations were given by gastric gavage for 8 weeks. It has been clearly determined that the HFCS diet increased expressions of interleukin (IL)-6, IL-1ß, and tumor necrosis factor-α proinflammatory structures via lymphocyte infiltration by suppressing antioxidant enzymes such as catalase, superoxide dismutase, and glutathione peroxidase in both tissues. Kefir improved these undesirable changes in rats fed with HFCS. The results of this current study, the first investigation to examine the effects of kefir on masseter muscle and gingival tissue, may provide new access to the restorative effects of kefir consumption on oral health disorders caused by high fructose in the diet. PRACTICAL APPLICATIONS: In this study, at an early age, the effects of kefir on improving inflammation via antioxidation in the masseter muscle and gingival tissue were investigated for the first time. We showed that kefir feeding ameliorates lymphocyte infiltration on the high-fructose corn syrup (HFCS)-induced masseter muscle and gingival tissue inflammation in rats. The mRNA expressions of inflammatory parameters measured in the study were supported by protein measurements via ELISA or immunohistochemistry. In the present study, kefir may play an important role in the antioxidation and inflammation process on the masseter muscle and gingival tissue against HFCS.

Sarcoidosis and Gullain-Barré syndrome.

A 35-year-old female presented with three days' history of aching discomfort in her back, chest, and ankles. She had also noticed increasing weakness of her legs and a week before admission had shown flu-like symptoms. Chest X-ray showed bilateral hilar and right paratracheal lymphadenopathy. Bronchoscopic biopsies revealed non-caseating granuloma. She was diagnosed with sarcoidosis and was given prednisolone. The patient developed facial palsy and rapidly progressive ascending paralysis beginning from the lower extremities on the third and fourth days after initial presentation, respectively. Analysis of lumbar puncture showed acellular fluid with a high protein content. EMG was consistent with diffuse sensorimotor demyelinating polyneuropathy. Thus, the diagnosis was Guillain-Barré syndrome (GBS) presenting with sarcoidosis. Intravenous immune globulin was given and prednisolone stopped. One month after initial presentation the patient was completely recovered and discharged on prednisolone therapy. If neurologic symptoms such as aching discomfort and weakness are the main complaints in patients with suspected or biopsy proven sarcoidosis, GBS should be suspected.

Effect of buscopan, a compound that alleviates cramps, on the developing nervous system of the chick embryo.

BACKGROUND: Buscopan is used to treat stomach cramps including those resulting from irritable bowel syndrome, bladder cramps, and pain related to menstruation. Its pregnancy category is determined as C. It has been shown in experimental animal studies that the drug has a negative effect on the embryo, but sufficient and well-controlled studies have not been conducted in humans. The aim of this study is to investigate effects of buscopan on the development of the neural tube (NT) in chick embryos. METHODS: Sixty specific pathogen-free (SPF) fertilized eggs were used. SPF eggs were placed in an incubator and divided into six groups at 28 hr of incubation. Five different doses (low to high) of buscopan were injected sub-blastodermally. At the end of 48 hr, the embryos were evaluated morphologically and histopathologically. The argyrophilic nucleolar-organizing region (AgNOR) method was used in this study to determine the proliferation activity of cells in NT development in chick embryos. AgNOR number and total AgNOR area/nuclear area (TAA/NA) were detected for each embryo. RESULTS: Depending on the dose, the embryo's crown-rump length and somite number decreased (p < .05). Significant differences were detected among all groups for mean AgNOR number (p < .05) and TAA/NA ratio (p < .05). CONCLUSIONS: Considering the average count of AgNOR cells and TAA/NA ratio, it was found that there was a decrease in cell division depending on the dose. It was determined that buscopan treatment on chick embryos adversely affected early nervous system and NT development.

Impact of Bisphenol A on neural tube development in 48-hr chicken embryos.

OBJECTIVES: Bisphenol A (BPA) is one of the most heavily produced chemicals in the world. BPA is involved in the production of many substances such as cosmetics, various foodstuffs, toys, personal care products, detergents and plastic bottles all that are frequently used in daily life. Depending on BPA exposure, sexual maturation and reproductive function, and bone and brain development are adversely affected. The aim of this study is to investigate the possible effects of BPA on the development of the nervous system and neural tube in 48-hr chicken embryos. METHODS: Thirty specific pathogen-free (SPF) fertilized eggs were used in the study. SPF eggs were placed in the incubator and divided into three groups at 28 hr of incubation; control, BPA 1 and BPA 2 (10 eggs in each group). At this stage of incubation, two different doses of BPA were injected sub-blastodermically with the Hamilton microinjector. At the end of 48 hr of incubation, all eggs were opened and embryos were dissected and separated from the embryonic membrane. All embryos were evaluated morphologically and histopathologically. RESULTS: As the BPA dose increased, delays in the development of the nervous system and midline closure increased in the early period of chicken embryos. Depending on the dose, it was found that the embryo's crown-rump length and somite number decreased (p < .05). CONCLUSION: It was determined that BPA application on early chicken embryos adversely affected neural tube development. It was also found to delay midline closure.

Anti-inflammatory and anti-apoptotic effect of nesfatin-1 on liver ischemia-reperfusion injury.

INTRODUCTION: Severe local and systemic tissue injury develop during reperfusion, which is a period during which arterial blood flow and tissue oxygenation are re-established. In this study, we aimed to investigate the anti-inflammatory, antioxidant and protective effects of nesfatin in IR damage developing in liver. MATERIAL AND METHODS: Twenty-four male Wistar-Albino rats were divided to three groups which contained eight rats in all groups. The rats were subjected to 30 minutes of hepatic pedicule occlusion followed by 2h of reperfusion to induce I/R damage. Nesfatin1 (10 µg/ kg) was administered, 30 min prior to ischemia and immediately before the reperfusion period. RESULTS: The findings showed that while the blood levels of AST, ALT and LDH were markedly elevated in the I/R group, they returned to normal levels upon treatment in the Nesfatin group. While IL-1 α, IL-1ß, IL-6, TNF-α and IFN- γ levels in blood and tissue were lower after therapy in the Nesfatin group compared to the I/R group, statistically significant decreases were only noted in IL-1ß, IL-6, TNF-α and IFN- γ levels. TAS levels increased in the treatment group, while upon nesfatin treatment statistically significant decreases were noted in TOS and OSI levels. Histopathological investigations also showed statistically significant decreases in Bax and Caspase-3 staining intensity and the number of stained cells in the Nesfatin group. CONCLUSION: The nesfatin has antioxidant activity and anti-inflammatory effect on improvement of liver functions and histopathological findings in liver ischemia and reperfusion injury. KEY WORDS: Anti-inflammatory, Anti apoptotic Liver ischemia-reperfusion injury, Nesfatin-1.

Potential Anti-Tumor Activity of Kefir-Induced Juglone and Resveratrol Fractions Against Ehrlich Ascites Carcinoma-Bearing BALB/C Mice.

We investigated the potential influence of kefir-induced juglone and resveratrol fractions (JRK) against Ehrlich Ascites Carcinoma (EAC) bearing BALB/c male mice. Kefir yeast was grown in the cell culture supplemented with juglone and resveratrol (1:2). After 48 h incubation, JRK solution was applied (0.1 mL/day i.p.) to the EAC-bearing mice throughout five days. Molecular regulatory mechanisms of apoptotic and anti-apoptotic pathway components were evaluated in the plasma of mice and isolated EAC cells with ELISA, qRT-PCR, and immunocytchemical experiments. EAC-induced upregulation in Bcl-2 and downregulation in Caspase-3 were normalized with JRK in the plasma of mice. Additionally, JRK upregulated the expression levels of apoptotic Bax, p53, Caspase-3,8,9, and APAF-1 proteins together with BAX, CASPASE-8, and CASPASE-9 genes in isolated EAC cells. These changes were also associated with decreased expression levels of anti-apoptotic Bcl-2 and Bcl-xl proteins. Immunocytochemical studies also confirmed the activation of apoptotic pathways and repression of anti-apoptotic proteins in EAC cells with JRK treatment. JRK activates apoptotic pathway and inhibits anti-apoptotic genes and proteins in Ehrlich ascites carcinoma- bearing BALB/c mice that could be beneficial in cancer treatment.

The novel model: Experimental optical coherence tomography-guided anterior segment imaging chick embryo model.

PURPOSE: The aim of this study was to present an experimental optical coherence tomography (OCT)-guided anterior segment (AS) imaging chick embryo model. Through this model, we aimed to reveal similarities and differences between human cornea, AS tissues, and chick embryo tissues by quantitative image analysis. METHODS: Ex vivo, the chick embryos' globes were determined by detailed AS camera of spectral-domain (SD)-OCT in 10 fertilized specific pathogen-free eggs on the 20th day. Quantitative image analysis of anterior chamber tissues was performed with SD-OCT in detail. After imaging, cross sections of the chick embryo globes containing cornea with anterior chamber were histologically examined and compared with human tissues. The similarities of our model with data in the human cornea and AS studies in the literature were compared. RESULTS: SD-OCT imaging was able to successfully delineate the AS tissues of chick embryos such as the cornea, iris, lens, pupil, conjunctiva, ciliary body, anterior chamber, and lens. Quantitative semi-automated measurements showed the following: mean central corneal thickness: 213.4 ± 7.05 µm (197-223 µm), mean anterior chamber depth: 878.9 ± 41.74 (804-919 µm), mean anterior chamber area: 2.43 ± 0.16 mm2 (2.17-2.73 mm2), mean corneoscleral junction (limbal) thickness: 322.8 ± 20.05 µm (289-360 µm), and mean iris thickness: 230.4 ± 13.27 µm (203-245 µm). In addition, detailed histological comparisons of the AS tissues with human tissues were evaluated to be very similar. CONCLUSION: In conclusion, this chick embryo model mimics human tissues and it can be considered as a platform for the study of teratogen-induced malformations and AS dysgenesis during gestation of AS tissues. In addition, this study demonstrates the feasibility of SD-OCT in the quantitative assessment of AS structures in chick embryo model.

Effects of 2-Aminoethyl Diphenylborinate, a Modulator of Transient Receptor Potential and Orai Channels in Subarachnoid Hemorrhage: An Experimental Study.

BACKGROUND: Cerebral vasospasm remains a serious problem affecting morbidity and mortality in patients with subarachnoid hemorrhage (SAH) during neurosurgery. We aimed to demonstrate the role of the transient receptor potential channel and other channels for Ca2+ in the etiology of cerebral vasospasm using 2-aminoethyl diphenylborinate (2-APB) and the effective dose range of an unstudied pharmacological agent, which can limit vasospasm. METHODS: We performed an experimental study using 32 Sprague-Dawley rats divided into 4 groups: sham group (n = 8), SAH group (n = 8), 2-APB group (SAH rats intraperitoneally administered with 0.5 mg/kg 2-APB; n = 8), and 2-APB-2 group (SAH rats intraperitoneally administered with 2 mg/kg 2-APB; n = 8). The rats were sacrificed after 24 hours, and superoxide dismutase, glutathione peroxidase, malondialdehyde, tumor necrosis factor-α, and interleukin-1ß in the brain tissue and serum were measured. The histopathological investigation of brain tissue included measurement of the luminal diameter and wall thickness of the basilar artery (BA), and apoptotic cells in the hippocampus were counted after caspase staining. RESULTS: Autologous arterial blood injection into the cisterna magna caused vasospasm in rats. 2-APB treatment increased the BA wall thickness and reduced the BA lumen diameter, inducing significant vascular changes. 2-APB also alleviated cell apoptosis at 24 hours after SAH. CONCLUSION: In experimental SAH in rats, 2-APB treatment increased the BA wall thickness and reduced the BA lumen diameter, inducing significant vascular changes. 2-APB also alleviated cell apoptosis at 24 hours after SAH.