No abstract

Background A recently discovered hormone, irisin is accepted to be significantly involved in the regulation of body weight. Thyroid functions may be, directly or indirectly, associated with irisin. Aim The aim of the present study is to determine the effect of experimental thyroid dysfunction on irisin levels in rats. Methods The study registered 40 adult male Sprague-Dawley rats, which were allocated to groups as follows: 1. Control; 2. Hypothyroidism induced by injection of 10 mg/kg/day intraperitoneal propylthiouracil (PTU) for 3 weeks; 3. Hypothyroidism (PTU 2 weeks) + L-thyroxin (1.5 mg/kg/day for 1 week); 4. Hyperthyroidism induced in rats by 3-week thyroxin (0.3 mg/kg/day); 5. Hyperthyroidism + PTU. At the end of the study, blood samples were collected to quantify free triiodothyronine (FT3), free triiodothyronine (FT4) and irisin levels. Results FT3 and FT4 levels were reduced in hypothyroidism and were significantly elevated in hyperthyroidism (p < 0.001). Irisin values, on the other hand, were found to be elevated in both hypothyroidism and hyperthyroidism groups (p < 0.001). Conclusion The results of the study suggest that irisin values increase in thyroid dysfunction, hypo- and hyperthyroidism, and that when hypothyroidism is corrected by thyroxin administration and hyperthyroidism by PTU injection, plasma irisin values go back to normal.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most common malignant tumors of the pancreas. Preclinical studies show that it evades the immune system with immune checkpoints and promotes tumor development. V-domain Ig suppressor of T cell activation (VISTA) is a new immunecheck point from the B7 family and is highly expressed in cancer cells. Overexpression of toll like receptor 4 (TLR4) in pancreatic adenocarcinoma is associated with inducing tumorigenesis, tumor growth and resistance to chemotherapy. Naloxone is an opioid and inhibits TLR4-ligand association. In this study, we investigated the connection of TLR4 and downstream pathway with immune-check point VISTA in pancreatic cancer proliferation. We rst collected pancreatic cancer-related datasets using the GEPIA2 and UALCAN databases. Based on the data obtained the effect of different concentrations and incubation times of Naloxone were used on PANC-1 cells proliferation. Combination of Naloxone and VISTA-siRNA were applied, and effect of both Naloxone and combined reatment on TLR4, Interleukin 1 receptor associated kinase 4 (IRAK4) and VISTA gene expression were analysed in pancreatic cancer cells. As a result of analysis with Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR), gene expression levels of TLR4, IRAK4 and VISTA were signi cantly suppressed and cell proliferation was signi cantly reduced. We found that administration of Naloxone and VISTA-siRNA in combination to PDAC cells suppressed signaling. Therefore, we considered that the relationship between VISTA and TLR4 signaling pathways and the other possible associated signal molecules may be an important marker in determining the response of immune checkpoint inhibitors in cancer treatment.

Irisin is a newly discovered myokine and adipokine that increases total body energy expenditure. The aim of this study was to determine the effect of experimental hypothyroidism and hyperthyroidism on the levels of irisin in heart tissue in rats. The study was performed on the 40 male Sprague-Dawley rats. Experimental groups were designed as; Control, Hypothyroidism, Hypothyroidism+L-Thyroxine, Hyperthyroidism and Hyperthyroidism + PTU. Following 3 weeks experimental period, irisin levels were determined in heart tissues. Hypothyroidism group values of irisin were higher than in the control group, but lower than in the hyperthyroidism group. The hyperthyroidism group had the highest levels of cardiac irisin. The results of the study showed that the experimental hypothyroidism and hyperthyroidism increased the heart irisin levels, but the increase in the hyperthyroidism group was much higher than in the hypothyroidism group. However, treatment of hypothyroidism and hyperthyroidism corrected cardiac irisin levels (Fig. 1, Ref. 28).

Background Changes in thyroid hormone concentrations may affect adiponectin concentrations through various mechanisms. A molecule released primarily from the fat cells adiposities; adiponectin has important effects on the regulation of body weight. Aim The present study aimed to explore the effects of experimental thyroid dysfunction and its treatment on nesfatin-1 and adiponectin levels in rats. Methods The study included 40 adult male Sprague-Dawley rats which were grouped as follows: (1) control; (2) hypothyroidism [hypothyroidism was induced by intraperitoneal injection of 10 mg/kg/day propylthiouracil (PTU) for 3 weeks]; (3) hypothyroidism + thyroxine group [after hypothyroidism was induced by 2-week PTU injection, they were treated with high-dose L-thyroxine (1.5 mg/kg/day) for 1 week]; (4) hyperthyroidism [hyperthyroidism was induced by 3-weeks' thyroxine injection (0.3 mg/kg/day)]; (5) hyperthyroidism + PTU (after hyperthyroidism was induced by 2-weeks' thyroxine injection, the animals were given 10 mg/kg/day PTU for 1 week). Blood samples taken at the end of the study were analyzed to measure nesfatin-1 and adiponectin levels. Results It was found that nesfatin-1 levels increased in hypothyroidism, while adiponectin levels decreased (p < 0.001). In experimental hyperthyroidism, on the other hand, both nesfatin-1 and adiponectin levels were found significantly elevated (p < 0.001). Conclusion The results of the study indicate that nesfatin-1 and adiponectin levels were modified considerably in hypo- and hyperthyroidism, whereas with the restoration of the thyroid function, modified hormone levels went back to normal.