Thyroid volume in Turkish school-age children living in an iodine-sufficient region.

OBJECTIVES: We aimed to obtain local normative data on thyroid volume evaluated by ultrasonography and iodine status by measuring urine iodine levels in school-age children living in Aydin province. METHODS: In this cross-sectional study, a sample comprising 1,553 cases was meticulously selected from a total cohort of 170,461 children aged 6-17, drawn from 21 distinct educational institutions located within the Aydin region, as participants in the investigation. Those with a known chronic disease or thyroid disease were excluded from the study. The children underwent physical examinations and ultrasonography imaging of the thyroid gland, and urine samples were collected to measure urinary iodine concentration (UIC). RESULTS: The median UIC was 189.5 (IQR=134.4) µg/L, which was optimal according to WHO criteria. Thyroid volume was found to be 4.6 (IQR=3.5) mL in girls and 4.2 (IQR=4.0) mL in boys (p=0.883). The thyroid volumes in our study were found to be smaller when compared to the WHO. According to WHO age and body surface area criteria, thyroid volume was over 97 % in 0.9 % (n=15) of cases. Thyroid volume was found to have a positive correlation with age, height, weight, body mass index (BMI), and body surface area (BSA) in both genders (p<0.001). However, there was no significant correlation between thyroid volume and UIC. CONCLUSIONS: This cross-sectional study provides normative data on thyroid volume and iodine status in school-age children in iodine-sufficient population, revealing a low prevalence of goiter and correlations between thyroid volume and anthropometric measures.

Neuropeptide W facilitates chronic gastric ulcer healing by the regulation of cyclooxygenase and NF-κB signaling pathways.

AIMS: Putative beneficial effects of neuropeptide W (NPW) in the early phase of gastric ulcer healing process and the involvement of cyclooxygenase (COX) enzymes were investigated in an acetic acid-induced gastric ulcer model. MAIN METHODS: In anesthetized male Sprague-Dawley rats, acetic acid was applied surgically on the serosa and then a COX-inhibitor (COX-2-selective NS-398, COX-1-selective ketorolac, or non-selective indomethacin; 2 mg/kg/day, 3 mg/kg/day or 5 mg/kg/day; respectively) or saline was injected intraperitoneally. One h after ulcer induction, omeprazole (20 mg/kg/day), NPW (0.1 µg/kg/day) or saline was intraperitoneally administered. Injections of NPW, COX-inhibitors, omeprazole or saline were continued for the following 2 days until rats were decapitated at the end of the third day. KEY FINDINGS: NPW treatment depressed gastric prostaglandin (PG) I2 level, but not PGE2 level. Similar to omeprazole, NPW treatment significantly reduced gastric and serum tumor necrosis factor-alpha and interleukin-1 beta levels and depressed the upregulation of nuclear factor kappa B (NF-κB) and COX-2 expressions due to ulcer. In parallel with the histopathological findings, treatment with NPW suppressed ulcer-induced increases in myeloperoxidase activity and malondialdehyde level and replenished glutathione level. However, the inhibitory effect of NPW on myeloperoxidase activity and NPW-induced increase in glutathione were not observed in the presence of COX-1 inhibitor ketorolac or the non-selective COX-inhibitor indomethacin. SIGNIFICANCE: In conclusion, NPW facilitated the healing of gastric injury in rats via the inhibition of pro-inflammatory cytokine production, oxidative stress and neutrophil infiltration as well as the downregulation of COX-2 protein and NF-κB gene expressions.

Associations of Adipocyte-Derived Versican and Macrophage-Derived Biglycan with Body Adipose Tissue and Hepatosteatosis in Obese Children.

Objective: In animal models of obesity, adipocyte-derived versican, and macrophage-derived biglycan play a crucial role in mediating adipose tissue inflammation. We aimed to investigate the levels of versican and biglycan in obese children and their potential association with body adipose tissue and hepatosteatosis. Methods: Serum levels of versican, biglycan, IL-6, and hsCRP were measured using the ELISA method. The fat deposition in the liver, spleen, and subcutaneous adipose tissue was calculated using the IDEAL-IQ sequences of MRI. Bioimpedance analysis was performed using the Tanita BC 418 MA device. Results: The study included 36 obese and 30 healthy children. Serum levels of versican, hsCRP, and IL-6 were higher in the obese group, while no significant difference was found in biglycan levels between the groups. There was a positive correlation between versican, biglycan, hsCRP, and IL-6. The MRI revealed higher segmental and global hepatic steatosis in obese children. There was no relationship between the hepatic fat content and versican, biglycan, IL-6, and hsCRP. Versican, biglycan, hsCRP, and IL-6 were not predictive of hepatosteatosis. Body fat percentage >32% provided a predictive sensitivity of 81.8% and a specificity of 70.5% for hepatosteatosis (AUC: 0.819, p<0.001). Similarly, a BMI SDS >1.75 yielded a predictive sensitivity of 81.8% and a specificity of 69.8% for predicting hepatosteatosis (AUC: 0.789, p<0.001). Conclusion: Obese children have higher levels of versican, hsCRP, and IL-6, and more fatty liver than their healthy peers. Body fat percentage and BMI SDS were the best predictors for hepatosteatosis in these children.

Efficacy of injectable platelet-rich fibrin on clinical and biochemical parameters in non-surgical periodontal treatment: a split-mouth randomized controlled trial.

OBJECTIVES: The purpose of this clinical trial was to evaluate the potential clinical and biochemical effects of injectable platelet-rich fibrin (i-PRF) application adjunct to scaling and root planning (ScRp) in deep periodontal pockets. MATERIALS AND METHODS: In this split-mouth-designed study, 17 patients with 34 deep periodontal pockets were randomly treated with ScRp + i-PRF (test group) and ScRp + saline (control group). Clinical periodontal measurements were recorded at baseline, 1st, 3rd, and 6th months after the treatments. The levels of vascular endothelial growth factor (VEGF), tumor necrosis factor-α (TNF-α), and interleukin (IL)-10 in gingival crevicular fluid (GCF) samples were analyzed using the ELISA method at baseline, 7th, and 14th days. RESULTS: Clinical periodontal parameters showed significant improvements with both treatment modalities. Mean pocket reduction (PD) and clinical attachment (CAL) gain were significantly higher in the test group than in controls at follow-up visits (p < 0.05). In the test group, gingival recession (GR) values were significantly lower compared to the control group. VEGF and IL-10 levels in the test group were significantly higher than in controls at the 14th day, and TNF-α levels were found significantly lower in the test group at the 7th and 14th days. CONCLUSIONS: Especially in the test group, the significant increase in VEGF and IL-10 expressions and the decrease in TNF-α levels may have accelerated the periodontal healing observed in the clinical parameters. CLINICAL RELEVANCE: The result of the present study demonstrated the beneficial effects of adjunctive i-PRF administration during non-surgical periodontal treatment of deep periodontal pockets. CLINICAL TRIAL REGISTRATION NUMBER: NCT05753631.

Synthesis, biological evaluation and molecular docking studies of novel 1,3,4-thiadiazoles as potential anticancer agents and human carbonic anhydrase inhibitors.

Thiosemicarbazide and also 1,3,4-thiadiazole derivatives have been garnering substantial attention from researchers worldwide due to their expansive range of biological activities, encompassing antimicrobial, anti-inflammatory, and anticancer properties. Herein, we embarked on a comprehensive investigation in this study, introducing a novel series of thiosemicarbazides (3a-3i) and their corresponding 1,3,4-thiadiazole (4a-4i) derivatives. The compounds were meticulously designed, synthesized, and subjected to meticulous characterization using various spectroscopic methods such as FT-IR, 1H-NMR, 13C-NMR, and elemental analysis. Afterward, their potential anti-proliferative effectiveness was assessed using MTT assay against two cancer cell lines (U87 and HeLa) and normal fibroblast cells (L929). Among the compounds, 4d showed the highest cytotoxic activity against U87 and 4i against HeLa. Compound 3b exhibited selective cytotoxic activity against both cancer cells. Among the molecules with selective activity against the U87 cell line; 3a, 3b, 4d and 4e were further evaluated by caspase-3 activity levels, Bax and Bcl-2 protein expression, and total oxidant status assay. Besides, carbonic anhydrase IX activity studies were also performed in order to understand the underlying mechanism of action. The results indicated that compound 4e showed higher efficacy than standard acetazolamide (IC50 = 0.58 ± 0.02 µM) with an IC50 value of 0.03 ± 0.01 µM. Furthermore, molecular docking studies were carried out using carbonic anhydrase IX crystals to determine the compound's interactions with the enzyme's active sites. This comprehensive investigation sheds light on the intricate interplay between molecular structure and biological activity, providing valuable insights into the therapeutic potential of these compounds.

Myokines as mediators of exercise-induced cognitive changes in older adults: protocol for a comprehensive living systematic review and meta-analysis.

Background: The world's population is aging, but life expectancy has risen more than healthy life expectancy (HALE). With respect to brain and cognition, the prevalence of neurodegenerative disorders increases with age, affecting health and quality of life, and imposing significant healthcare costs. Although the effects of physical exercise on cognition in advanced age have been widely explored, in-depth fundamental knowledge of the underlying mechanisms of the exercise-induced cognitive improvements is lacking. Recent research suggests that myokines, factors released into the blood circulation by contracting skeletal muscle, may play a role in mediating the beneficial effect of exercise on cognition. Our goal in this ongoing (living) review is to continuously map the rapidly accumulating knowledge on pathways between acute or chronic exercise-induced myokines and cognitive domains enhanced by exercise. Method: Randomized controlled studies will be systematically collected at baseline and every 6 months for at least 5 years. Literature search will be performed online in PubMed, EMBASE, PsycINFO, Web of Science, SportDiscus, LILACS, IBECS, CINAHL, SCOPUS, ICTRP, and ClinicalTrials.gov. Risk of bias will be assessed using the Revised Cochrane Risk of Bias tool (ROB 2). A random effects meta-analysis with mediation analysis using meta-analytic structural equation modeling (MASEM) will be performed. The primary research question is to what extent exercise-induced myokines serve as mediators of cognitive function. Secondarily, the pooled effect size of specific exercise characteristics (e.g., mode of exercise) or specific older adults' populations (e.g., cognitively impaired) on the relationship between exercise, myokines, and cognition will be assessed. The review protocol was registered in PROSPERO (CRD42023416996). Discussion: Understanding the triad relationship between exercise, myokines and cognition will expand the knowledge on multiple integrated network systems communicating between skeletal muscles and other organs such as the brain, thus mediating the beneficial effects of exercise on health and performance. It may also have practical implications, e.g., if a certain myokine is found to be a mediator between exercise and cognition, the optimal exercise characteristics for inducing this myokine can be prescribed. The living review is expected to improve our state of knowledge and refine exercise regimes for enhancing cognitive functioning in diverse older adults' populations. Registration: Systematic review and meta-analysis protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) on the 24th of April 2023 (registration number CRD42023416996).

Piperazin incorporated Schiff Base derivatives: Assessment of in vitro biological activities, metabolic enzyme inhibition properties, and molecular docking calculations.

The cytotoxic activities of the compounds were determined by the 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) method in human breast cancer (MCF-7), human cervical cancer (HeLa), and mouse fibroblast (L929) cell lines. The compounds MAAS-5 and four modified the supercoiled tertiary structure of pBR322 plasmid DNA. MAAS-5 showed the highest cytotoxic activity in HeLa, MCF-7, and L929 cells with IC50 values of 16.76 ± 3.22, 28.83 ± 5.61, and 2.18 ± 1.22 µM, respectively. MAAS-3 was found to have almost the lowest cytotoxic activities with the IC50 values of 93.17 ± 9.28, 181.07 ± 11.54, and 16.86 ± 6.42 µM in HeLa, MCF-7, and L929 cells respectively at 24 h. Moreover, the antiepileptic potentials of these compounds were investigated in this study. To this end, the effect of newly synthesized Schiff base derivatives on the enzyme activities of carbonic anhydrase I and II isozymes (human carbonic anhydrase [hCA] I and hCA II) was evaluated spectrophotometrically. The target compounds demonstrated high inhibitory activities compared with standard inhibitors with Ki values in the range of 4.54 ± 0.86-15.46 ± 8.65 nM for hCA I (Ki value for standard inhibitor = 12.08 ± 2.00 nM), 1.09 ± 0.32-29.94 ± 0.82 nM for hCA II (Ki value for standard inhibitor = 18.22 ± 4.90 nM). Finally, the activities of the compounds were compared with the Gaussian programme in the B3lyp, HF, M062X base sets with 6-31++G (d,p) levels. In addition, the activities of five compounds against various breast cancer proteins and hCA I and II were compared with molecular docking calculations. Also, absorption, distribution, metabolism, excretion, and toxicity analysis was performed to investigate the possibility of using five compounds as drug candidates.

Gingival crevicular fluid periodontal ligament-associated protein-1, sclerostin, and tumor necrosis factor-alpha levels in periodontitis.

BACKGROUND: In periodontitis, the equilibrium between bone formation and resorption skews in favor of bone loss. Periodontal ligament-associated protein-1 (PLAP-1) and sclerostin play a significant role in the suppression of bone formation. Tumor necrosis factor-alpha (TNF-α) is a central proinflammatory cytokine related to periodontal bone loss. This study aims to assess gingival crevicular fluid (GCF) PLAP-1, sclerostin, and TNF-α levels in individuals with periodontal disease. METHODS: Seventy-one individuals diagnosed with generalized stage III grade C periodontitis (n = 23), gingivitis (n = 24), and periodontal health (n = 24) were included in the study. Full-mouth clinical periodontal measurements were performed. PLAP-1, sclerostin, and TNF-α total amounts in GCF were quantified by ELISA. Nonparametric methods were used for the data analyses. RESULTS: Periodontitis group exhibited significantly higher GCF PLAP-1, sclerostin and TNF-α levels compared with gingivitis and periodontally healthy groups (p < 0.05). GCF PLAP-1 and TNF-α levels of gingivitis group were higher than healthy controls (p < 0.05) whereas GCF sclerostin levels were similar in two groups (p > 0.05). Significant positive correlations were found between GCF PLAP-1, sclerostin and TNF-α levels and all clinical parameters (p < 0.01). CONCLUSIONS: To our knowledge, this is the first study showing GCF PLAP-1 levels in periodontal health and disease. Increased GCF PLAP-1 and sclerostin levels and their correlations with TNF-α in periodontitis imply that those molecules might be involved in the pathogenesis of periodontal disease. Further studies in larger mixed cohorts are needed to enlighten the possible role of PLAP-1 and sclerostin in periodontal bone loss.

Therapeutic and prophylactic role of vitamin D and curcumin in acetic acid-induced acute ulcerative colitis model.

Ulcerative Colitis (UC) is a disease that negatively affects quality of life and is associated with sustained oxidative stress, inflammation and intestinal permeability. Vitamin D and Curcumin; It has pharmacological properties beneficial to health, including antioxidant and anti-inflammatory properties. Our study investigates the role of Vitamin D and Curcumin in acetic acid-induced acute colitis model. To investigate the effect of Vitamin D and Curcumin, Wistar-albino rats were given 0.4 mcg/kg Vitamin D (Post-Vit D, Pre-Vit D) and 200 mg/kg Curcumin (Post-Cur, Pre-Cur) for 7 days and acetic acid was injected into all rats except the control group. Our results; colon tissue TNF-α, IL-1ß, IL-6, IFN-γ and MPO levels were found significantly higher and Occludin levels were found significantly lower in the colitis group compared to the control group (p < 0.05). TNF-α and IFN-γ levels decreased and Occludin levels increased in colon tissue of Post-Vit D group compared to colitis group (p < 0.05). IL-1ß, IL-6 and IFN-γ levels were decreased in colon tissue of Post-Cur and Pre-Cur groups (p < 0.05). MPO levels in colon tissue decreased in all treatment groups (p < 0.05). Vitamin D and Curcumin treatment significantly reduced inflammation and restored the normal histoarchitecture of the colon. From the present study findings, we can conclude that Vitamin D and Curcumin protect the colon from acetic acid toxicity with their antioxidant and anti-inflammatory potential.Brief synopsis: In this study; distal colon, distal ileum, jejunum and serum physiopathology in colitis induced by acetic acid and intestinal permeability were investigated. The roles of vitamin D and curcumin in this process were evaluated.

Association of chondroadherin with leiomyosarcoma.

The leiomyosarcoma (LMS) subtype of uterine sarcoma accounts for 1-2 % of uterine neoplasia cases. The present study aimed to demonstrate that the gene and protein chondroadherin (CHAD) levels may serve as novel biomarkers for predicting prognosis and devising novel treatment models for LMS. A total of 12 patients diagnosed with LMS and 13 patients diagnosed with myomas were included in the study. The extent of tumour cell necrosis, cellularity and atypia and the mitotic index of each patient with LMS were determined. CHAD gene expression was significantly increased in cancerous tissues compared with that in fibroid tissues (2.17 ± 0.88 vs 3.19 ± 1.61; P = 0.047). The mean CHAD protein expression in tissues was higher in LMS cases but this was not statistically significant (217.38 ± 93.9 vs 177.13 ± 66.67;P = 0.226). Positive significant correlations were obtained between CHAD gene expression and mitotic index (r = 0.476; P = 0.008), tumour size (r = 0.385; P = 0.029) and necrosis (r = 0.455; P = 0.011). Furthermore, there were significant positive correlations between CHAD protein expression levels and tumour size (r = 0.360; P = 0.039) and necrosis (r = 0.377; P = 0.032). The present study was the first to demonstrate the significance of CHAD in LMS. The results suggested that, due to its association with LMS, CHAD has predictive value in determining the prognosis of patients with LMS.

Cotinus coggygria Scop. Attenuates Acetic Acid-Induced Colitis in Rats by Regulation of Inflammatory Mediators.

In traditional medicine, many medicinal plants are used in the treatment of various diseases caused by inflammation. The objective of the present study is to elucidate for the first time the effects of Cotinus coggygria (CC) ethanol extract (CCE) on colonic structure and inflammation of acetic acid-induced ulcerative colitis in rats. Colonic damage was assessed using disease activity index score, enzyme-linked immunosorbent assay, and hematoxylin-eosin staining. Also, in vitro antioxidant activity of CCE was investigated by ABTS methods. Total phytochemical content of CCE was measured spectroscopically. Acetic acid caused colonic damage according to disease activity index and macroscopic scoring. CCE significantly reversed these damages. While the levels of proinflammatory cytokines TNF-alpha, IL-1beta, IL-6, and TGF-1beta increased in tissue with UC, IL-10 level decreased. CCE increased inflammatory cytokine levels to values close to the sham group. At the same time, while markers indicating disease severity such as VEGF, COX-2, PGE2, and 8-OHdG indicated the disease in the colitis group, these values returned to normal with CCE. Histological research results support biochemical analysis. CCE exhibited significant antioxidant against ABTS radical. Also, CCE was found to have a high content of total polyphenolic compounds. These findings provide evidence that CCE might be benefit as a promising novel therapy in the treatment of UC in humans due to high polyphenol content and justify the use of CC in folkloric medicine for treatment of inflamed diseases.

Neuropeptide W Exhibits Preventive and Therapeutic Effects on Acetic Acid-Induced Colitis via Modulation of the Cyclooxygenase Enzyme System.

BACKGROUND: The novel peptide neuropeptide W (NPW) was originally shown to function in the control of feeding behavior and energy homeostasis. The aim of this study was to elucidate the putative preventive and therapeutic effects of NPW on colitis-associated oxidative injury and the underlying mechanisms for its action. METHODS: Sprague-Dawley rats in the acute colitis groups received NPW (0.5, 1 or 5 µg/kg/day) injections prior to induction of colitis with acetic acid, while the chronic colitis groups were treated after the induction of colitis. In both acute and chronic colitis (CC) groups, treatments were continued for 5 days and the rats were decapitated at the 24th hour of the last injections and colon tissues were collected for assessments. RESULTS: NPW pretreatment given for 5 days before colitis induction, as well as treating rats with NPW during the 5-day course of CC, abolished colonic lipid peroxidation. NPW treatment prevented colitis-induced reduction in blood flow, diminished neutrophil infiltration, and pro-inflammatory cytokine responses. NPW pretreatment only at the higher dose reduced colonic edema and microscopic score and preserved colonic glutathione stores. Elevations in cyclooxygenase (COX) enzyme activity and COX-1 protein level during the acute phase of colitis as well as reduction in COX-2 were all reversed with NPW pretreatment. In contrast, NPW treatment was effective in reducing the elevated COX-2 concentration during the chronic phase. CONCLUSIONS: NPW alleviates acetic acid-induced oxidative colonic injury in rats through the upregulation of colonic blood flow as well as the inhibition of COX-2 protein expression and pro-inflammatory cytokine production.

Maternal separation increased memory function and anxiety without effects of environmental enrichment in male rats.

Maternal separation is a detrimental postnatal influence, whereas environmental enrichment is a therapeutic and protective agent. It is unclear if long-term environmental enrichment can compensate for the effects of maternal separation stress on memory-related alterations. This study examined how environmental enrichment affected memory functions, anxiety level, Grin2a, Grin2b, BDNF, and cFos expressions in the maternally separated rats. There are seven groups in this study: control (C), maternal separation+standard cage (MS), maternal separation + enriched cage (MSE), enriched cage (E), the maternal separation that decapitated at postnatal 21 (MS21) and standard cage that decapitated at PN21 (C21) for hormone and gene expression analysis. The maternal separation procedure consisted of postnatal 21 days. Learning and memory performance were determined with the Morris water tank test; anxiety and locomotor activity were examined with the open field and elevated plus-maze test. The expression levels of genes were measured by the RT-PCR method. Blood corticosterone level was evaluated by the ELISA method. Results showed that MS increased memory performance, locomotor activity, and anxiety, but it did not change gene expression levels. An enriched environment did not change the memory performance, locomotor activity, and related gene expression levels. MSE group increased their memory performance, but the anxiety, locomotor activity, and gene expression level did not change. Grin2a, Grin2b, and BDNF gene expression and corticosterone levels increased in the MS21 group. Maternal separation increased memory performance, but it also increased anxiety. Environmental enrichment alone was insufficient to cause alterations in the memory performance.

Hyperthyroidism leads learning and memory impairment possibly via GRIN2B expression alterations.

The hippocampus as an important structure for learning and memory functions contains a high level of thyroid hormone receptors. Although there are numerous studies investigating the effects of thyroid hormones on cognitive dysfunction and psychiatric symptoms, the underlying molecular processes of these disorders have not yet been fully elucidated. In the present study, 24 male adult rats (4 months) were divided into 3 groups: control group, sham group and hyperthyroid group. Hyperthyroid group and sham group were treated with l-thyroxine or saline for 21 days. Each group was exposed to Morris water maze testing (MWMT), measuring their performance in a hidden-platform spatial task. After learning and memory tests, intracardiac blood was taken from the rats for serum thyroxine levels. Following blood collection, the rats were decapitated to isolate hippocampal tissue. GRIN2A, GRIN2B, BDNF, cFOS, Cdk5, cdk5r1 (p35), and cdk5r2 (p39) gene expression were evaluated using quantitative reverse transcriptase-PCR. Serum thyroxine level was found to be higher in hyperthyroid rats than in the control and sham groups. According to our MWMT findings, the memory performance of the hyperthyroid group was significantly impaired compared to the control and sham groups (p < 0.05). In the hippocampus, the GRIN2A gene expression level was decreased in the sham group, and the GRIN2B gene expression level was decreased in the sham and hyperthyroid groups compared to the control group (p < 0.05). There was no significant difference in other genes (p > 0.05). Hyperthyroidism impaired hippocampus-dependent spatial memory. Hyperthyroidism caused decreased level of GRIN2B gene expression in the hippocampus.

Hepatoprotective effects of parsley (Petroselinum Crispum) extract in rats with bile duct ligation.

BACKGROUND AND STUDY AIMS: This study aimed to investigate the possible protective effects of parsley extract (Petroselinum Crispum; PC) against oxidative liver damage caused by bile obstruction in rats. MATERIAL AND METHODS: Bile duct ligation (BDL) method was used to induce liver injury in rats. The rats were divided into the three groups each consisting of 8 rats; Sham-operated control (C), bile duct ligated + saline treated (BDL), and BDL + PC treated groups. PC extract was given at a dose of 2 g/kg orally for 28 days. Aspartate amino transferase (AST), alanin amino transferase (ALT), and bilirubin levels were analyzed in sera. In order to determine free radicals in liver injury, luminol and lucigenin chemiluminescence tests used. Oxidative stress was evaluated through superoxide dismutase, glutathione, malondialdehyde, Na+/K+-ATPase and 8-hydroxy guanosine levels. Furthermore, inflammation marker myeloperoxidase, apoptosis marker caspase-3, and fibrosis markers TGF- ß and hydoxyproline were investigated. The liver tissues were also examined for histological evaluations. RESULTS: While PC treatment decreased AST and ALT levels which increased with BDL, oxidant damage parameters also decreased with this treatment. CONCLUSION: The present study, which is the first research for PC extract on cholestasis induced liver damage, demonstrated that PC extract could be a potential therapeutic agent against liver fibrosis and need further studies.

Paricalcitol protects against hydrogen peroxide-induced injury in endothelial cells through suppression of apoptosis.

The vascular endothelium is one of the main targets of oxidative stress which plays an important role in the pathophysiology of vascular damage. Recent studies show that vitamin D can positively regulate endothelial functions in various chronic diseases and in cases of increased oxidative stress. In our study, we investigated the restorative and protective potentials of paricalcitol which is frequently used in patients with chronic renal failure, a vitamin D analogue, in human umbilical vein endothelial cells (HUVEC) before and after H2O2-induced oxidative stress. Paricalcitol treatment after the oxidative stress induced by H2O2 increased cell viability in endothelial cells depending on the dose that was used. While paricalcitol (500 nM) decreased caspase-3 activity and mitochondrial membrane potential loss, it increased nitric oxide (NO) production and reduced glutathione (GSH) levels. Paricalcitol treatment before oxidative stress increased cell viability. It increased NO production and mitochondrial membrane potential while significantly reducing caspase-3 activity. While paricalcitol caused a significant inhibition of protein disulfide isomerase (PDI) reductase activity in healthy endothelial cells, it did not cause a significant change on the PDI reductase activity under oxidative stress conditions. Present study showed that paricalcitol has restorative and protective effects on endothelial cells against oxidative injury, but these effects occur at high concentrations of paricalcitol.

Evaluation of Intrafollicular Syndecan 1, Glypican 3, and Spermidine Levels in Women with Diminished Ovarian Reserve.

We aimed to evaluate the levels of Spermidine, Syndecan 1, and Glypican 3 (GPC3) in the follicle fluid of women with diminished ovarian reserve (DOR) and to examine the relationship of these markers with the number of embryos and clinical pregnancy. A total of 27 women with DOR and 34 women with normal ovarian reserve who underwent in vitro fertilization procedure were included in this prospectively designed study. Spermidine, Syndecan 1, and GPC3 levels were studied in the follicle fluid samples taken from the women at the time of oocyte retrieval by ELISA method, and their relations with the cycle outcomes were examined. The mean age was found as 38.1 ± 7.4 years in the DOR group and 35.1 ± 5.2 years in the control group (p = 0.027). When adjusted for age and body mass index, while the median Spermidine level was significantly higher (p < 0.001), both Syndecan 1 (p < 0.001) and GPC3 (p = 0.006) were significantly lower in the DOR group compared with control group. The cut-off value of Spermidine for clinical pregnancy prediction was found as 74.08 ng/mL with 78.9% sensitivity and 57.1% specificity [OR: 5 (95% CI: 1.4-17.6); AUC: 0.621; p = 0.138], while it was 0.96 ng/mL with 84.2% sensitivity and 59.5% specificity [OR: 7.8 (95% CI: 2-31.1); AUC: 0.701; p = 0.004] for GP3 and 1.15 ng/mL with 78.9 sensitivity and 57.1% specificity [OR: 5 (95% CI: 1.4-17.6); AUC: 0.680; p = 0.009] for Syndecan 1. Intrafollicular spermidine, Syndecan 1, and GPC3 levels may have a role in ovarian aging. Further randomized controlled studies in a larger population are needed for the relationship of these markers with cycle and pregnancy outcomes.

Quercetin protects mouse oocytes against chromium-induced damage in vitro and in vivo.

BACKGROUND: Chromium (Cr) is a naturally-occurring element that is used in various fields of industry. Humans may be exposed to hexavalent chromium [Cr(VI)], which is one of the stable valence states of the chromium through contaminated soil, air, and water. Exposure to Cr(VI) through contaminated drinking water, soil and air causes various cancers and also fertility problems in animals and humans. Quercetin (QCT), a common flavonoid compound, has numerous biological effects as an antioxidant and free radical scavenger, but its function and mechanisms in reproductive processes in various species remain unclear. This study aims to determine the chromium effects on mice oocyte quality and the ameliorative effect of QCT in both in vitro and in vivo experimental models. METHODS: For the in vitro experiment, oocytes were collected and divided into the control, sham, QCT-treated, Cr(VI) (potassium dichromate), and treatment [Cr(VI)+QCT] groups. Collected oocytes were cultured in maturation medium with or without 10 µM quercetin and 10 µM Cr(VI) for 14 h based on the defined experimental design. For the in vivo experiment, the mice were randomly divided into the control, sham, QCT-treated, Cr(VI), and Cr(VI) + QCT groups. Control and sham mice received regular drinking water and diet. Cr(VI) group received Cr(VI) (50 ppm in drinking water) and Cr(VI) + QCT group received 50 ppm Cr(VI) with QCT (20 mg/kg body wt, through i.p) for a period of 21 days and then oocytes were collected and cultured for 14 h for in vitro maturation. For both experiments, at the end of the culture period, we examined the ameliorative effect of QCT on oocyte maturation, spindle formation, ROS production, mitochondrial function, and apoptosis. RESULTS: Our in vitro and in vivo results showed that Cr(VI) disrupt the oocyte maturation and spindle formation (P < 0.001). Furthermore, we found that exposure to Cr(VI) significantly increased ROS levels and decreased mitochondrial membrane potential (P < 0.001). In addition, exposure to Cr(VI) induced early apoptosis and downregulated the Bcl-2 mRNA expression and upregulated the Caspase-3 and Bax mRNAs expression (P < 0.01). Finally, quercetin significantly restored the detrimental effects of Cr(VI). CONCLUSION: The results indicated that quercetin protects the oocytes against Cr(VI) toxicity through the suppression of oxidative stress and apoptosis. The conclusions drawn from our study's findings suggest that quercetin might be useful agent for oocyte maturation in case of possible exposure to toxic substances such as chromium.

Synthesis and Biological Evaluation of Some Hydrazide-Hydrazone Derivatives as Anticancer Agents.

In this study, a series of hydrazide-hydrazone derivatives (3a-3u) were synthesized and evaluated for their anticancer activities against prostate cancer cell line (PC-3), breast cancer cell line (MCF-7), colon cancer cell line (HT-29) and human umbilical vein endothelial cells (HUVEC) using MTT assay. In particular, compound 3h having a pyrrole ring was found to be the most potent derivative with IC50 = 1.32, 2.99, 1.71 µM against PC-3, MCF-7, HT-29 cancer cell lines respectively using paclitaxel as a standard compound. Furthermore, compound 3h was subjected to further biological studies such as caspase-3 activity and Annexin-V assay to evaluate their inhibitory potentials. The activity results displayed that compound 3h increased caspase-3 activation and the number of cells to early apoptosis. The additional studies like pharmacokinetics, bioavailability scores and drug-likeness properties were also evaluated. The in silico pharmacokinetics predictions displayed that the bioavailability of these compounds may be high.

On-Chip Organoid Formation to Study CXCR4/CXCL-12 Chemokine Microenvironment Responses for Renal Cancer Drug Testing.

Organoid models have gained importance in recent years in determining the toxic effects of drugs in cancer studies. Organoid designs with the same standardized size and cellular structures are desired for drug tests. The field of microfluidics offers numerous advantages to enable well-controlled and contamination-free biomedical research. In this study, simple and low-cost microfluidic devices were designed and fabricated to develop an organoid model for drug testing for renal cancers. Caki human renal cancer cells and mesenchymal stem cells isolated from human umbilical cord were placed into alginate hydrogels. The microfluidic system was implemented to form size-controllable organoids within alginate hydrogels. Alginate capsules of uniform sizes formed in the microfluidic system were kept in cell culture for 21 days, and their organoid development was studied with calcein staining. Cisplatin was used as a standard chemotherapeutic, and organoid sphere structures were examined as a function of time with an MTT assay. HIF-1α, CXCR4 and CXCL-12 chemokine protein, and CXCR4 and CXCL-12 gene levels were tested in organoids and cisplatin responses. In conclusion, it was found that the standard renal cancer organoids made on a lab-on-a-chip system can be used to measure drug effects and tumor microenvironment responses.