Microarray profiling identifies hsa_circ_0082003 as a novel tumor promoter for papillary thyroid carcinoma.

BACKGROUND: Circular RNAs (circRNAs) are non-coding RNAs that have essential regulatory roles in the development of various tumors. This study explored whether circRNAs are involved in the progression of papillary thyroid carcinoma (PTC). METHODS: Differentially expressed circRNAs (DECs) in four pairs of PTC and matched normal thyroid tissues were screened using a circRNA microarray. The potential functions of dysregulated circRNAs were predicted by bioinformatic analyses. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was used to determine hsa_circ_0082003 expression in 80 pairs of PTC and matched normal thyroid tissues. Cell counting kit-8, colony formation, wound healing, and Transwell assays were performed to evaluate the biological functions of hsa_circ_0082003 in PTC cells. The role of hsa_circ_0082003 in PTC tumorigenesis in vivo was validated in nude mice. RESULTS: In total, 3150 DECs (2317 upregulated and 833 downregulated) were identified. Pathway enrichment analyses indicated that the dysregulated circRNAs may play roles in PTC development. RT-qPCR validation demonstrated that hsa_circ_0082003 expression was significantly increased in PTC tissues and correlated with poor clinicopathological parameters. Receiver operating characteristic curve analysis showed that hsa_circ_0082003 had good performance for diagnosing PTC and judging whether it was accompanied by lymph node metastasis. Knockdown of hsa_circ_0082003 inhibited PTC cell proliferation, migration, and invasion. Tumor formation assays in vivo showed that downregulation of hsa_circ_0082003 significantly suppressed the growth of PTC. CONCLUSION: Hsa_circ_0082003 may serve as a novel diagnostic biomarker and potential therapeutic target for PTC.

Nomograms based on sonographic and clinicopathological characteristics to predict lateral lymph node metastasis in classic papillary thyroid carcinoma.

BACKGROUND: Lateral lymph node metastasis (LLNM) has been considered a risk factor of recurrence in papillary thyroid cancer (PTC). Preoperative detecting LLNM accurately is difficult. Solitary lateral lymph node metastasis is a special type of LLNM. We aimed to develop nomograms for predicting LLNM and multiple lateral lymph node metastasis (MLLNM). METHODS: We retrospectively retrieved 528 classic PTC patients that underwent surgery between March 2019 and May 2020. Sonographic and clinicopathological features were collected. Risk factors of LLNM and MLLNM were determined by univariate and multivariate analysis. Nomograms for predicting LLNM and MLLNM were developed. RESULTS: LLNM was independently associated with tumor size, the number of foci, location, margin, central lymph node metastasis, and lymph node ratio. Independent predictors of MLLNM were age, margin, and the number of metastatic lymph nodes in central compartment. By using above variables, we constructed nomograms for predicting LLNM and MLLNM, with area under curves of 0.864 and 0.748, respectively. CONCLUSION: Through these accurate and easy-to-use nomograms, we can detect the risk of residual LLNM postoperatively for classic PTC patients who did not receive lateral neck dissection and provide an individualized plan for postoperative management of classic PTC patients.

Involvement of two distinct signalling pathways in IGF-1-mediated central control of hypotensive effects in normotensive and hypertensive rats.

AIMS: Insulin-like growth factor-1 (IGF-1) is abundantly expressed in the nucleus tractus solitarii (NTS). In a previous study, we revealed that the induction of nitric oxide (NO) production in the NTS reduces blood pressure (BP). It is well known that both acute administration and chronic administration of IGF-I reduce BP. The aim of this study was to evaluate the short-term hypotensive effect of IGF-1 in the NTS and to delineate the underlying molecular mechanisms of IGF-1 in the NTS of normotensive WKY rats and spontaneously hypertensive rats (SHRs). METHOD: Microinjections of the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 and the MAP kinase-ERK kinase (MEK) inhibitor PD98059 into the NTS in WKY rats and SHRs were used to study the involvement of IGF-1-induced depressor effects. RESULT: An IGF-1 (7.7 pmol) injection into the NTS resulted in a significant decrease in BP and HR in WKY rats and SHRs. Immunoblotting and immunohistochemical analysis showed that the microinjection of LY294002 (0.6 pmol) or PD98059 (3.0 pmol) into the NTS attenuated the IGF-1-induced depressor effects and Akt or ERK phosphorylation in WKY rats. An attenuation effect of LY294002, but not PD98059, was found in the SHRs. However, the mRNA and protein expression levels of the IGF-1R showed no significant differences in the NTS of the WKY rats and the SHRs. CONCLUSION: These results suggest that distinct Akt and ERK signalling pathways mediated the IGF-1 control of the central depressor effects in WKY rats and SHRs. ERK signalling defects may be associated with the development of hypertension.

Modulation of baroreflex function by rosiglitazone in prediabetic hyperglycemic rats.

Baroreflex sensitivity (BRS) is abnormal in the prediabetic state. This study was conducted to determine effects of chronic rosiglitazone (RSG), an insulin sensitizer, on BRS in prediabetic hyperglycemic (PDH) rats induced by nicotinamide and streptozotocin. The fasting and postprandial blood glucose levels were 5.6-6.9 and 7.8-11.0 mmol/l, respectively. Rats were treated with RSG or saline for 12 weeks. BRS response to phenylephrine (PE-BRS) or sodium nitroprusside (NP-BRS) was determined by linear regression method. Cardiac sympathetic and parasympathetic influences were determined by autonomic blockades. In the saline-treated PDH rats, PE-BRS was enhanced early at week 4 and became greater at week 12. Abnormalities in NP-BRS and cardiac autonomic influences were found only after week 12. Four weeks of RSG treatment normalized blood glucose levels but not PE-BRS. All altered cardiovascular variables were completely restored by 12 weeks of RSG treatment. The correlation between BRS and blood glucose levels in saline-treated PDH rats was significant at week 12, but no correlation was found in RSG-treated rats. In conclusion, hyperglycemia, even in the prediabetic state, may play a role in BRS abnormalities. RSG treatment early in the prediabetic state may normalize BRS via cardiac autonomic modulation, besides its anti-hyperglycemic action.

Neuroprotective effects of pioglitazone in a rat model of permanent focal cerebral ischemia are associated with peroxisome proliferator-activated receptor gamma-mediated suppression of nuclear factor-κB signaling pathway.

Previous studies have demonstrated that pioglitazone (Piog), a peroxisome proliferator-activated receptor gamma (PPARγ) agonist, inhibits ischemia-induced brain injury. Piog has also been shown to exert anti-inflammatory effects by attenuation of nuclear factor-κB (NF-κB) activation after myocardial ischemia/reperfusion injury. Because NF-κB is known to play a major role in the pathophysiology of brain ischemia, the present study was undertaken to elucidate whether pioglitazone attenuates ischemic neuronal damage through PPARγ-mediated suppression of NF-κB apoptotic signaling pathway. Permanent middle cerebral artery occlusion (pMCAO) model was induced by using an intraluminal filament technique in rats. Piog was administrated i.p. twice (24 h before and at the time of ischemia insult) or once (10 min after ischemia). The neuroprotection of Piog was analyzed by assessing neurological deficits, infarction volume and morphological changes. The inhibition of NF-κB signaling pathway by Piog was evaluated by detecting the nuclear translocation of NF-κB p65 with immunohistochemistry and its target gene p53 by real-time PCR, and the expression of phospholated NF-κB p65 (p- NF-κB p65) in primary cultured neurons and the protein levels of IκBα and p-ERK in the ischemic cortex or striatum with Western blotting analysis. The contribution of a PPARγ mechanism to Piog's inhibitory effects on NF-κB and neuroprotection was evaluated by pretreatment with the PPARγ irreversible antagonist GW9662. In vitro ischemia in cultured primary neurons was induced by the oxygen-glucose deprivation (OGD) and the protective effect of Piog on cultured neurons was measured by lactate dehydrogenase (LDH) assay. Piog (0.5, 1, 2 mg/kg) reduced infarction volume, and improved morphological changes and motor deficits. Piog markedly up-regulated the protein levels of IκBα or p-ERK 6 h or 12 h after ischemia. Piog reduced the nuclear translocation of NF-κB p65 in the ischemic cortical cells and repressed the expression of p53 12 h after ischemia. Pre-treatment with GW9662 blocked Piog-elicited reduction in infarction volume, the increase in protein levels of IκBα and p-ERK, the reduction in the nuclear translocation of NF-κB subunit p65 and the repression of p53 mRNA expression. In addition, Piog attenuated the OGD-induced neuronal damage and inhibited the OGD-induced increases in p- NF-κB p65 in neurons. The present findings suggest that Piog's neuroprotection appears to be associated with PPARγ-mediated suppression of NF-κB signaling pathway.

Mutagenic safety and fatty liver improvement of nanonized black soybeans in senescence-accelerated prone-8 mice.

Nanotechnology, as a new enabling technology, has the potential to revolutionize food systems. However, much attention has been focused on nanoparticle foods due to their potential physiological properties. This study was aimed to evaluate the mutagenic safety and fatty liver improvement of black soybean in senescence-accelerated mice (SAMP8). The mutagenic activity of black soybeans was investigated using the Ames test (Salmonella Typhimurium TA98, 100, 102, and 1535). Furthermore, senescence-accelerated prone-8 mice (SAMP8) have been reported to display spontaneous fatty liver. Male SAMP8 mice were divided into control and supplemented with 10% micronized or nanonized black soybeans diet and fed for 12 wk. The results revealed that the Ames test of micronized and nanonized black soybeans exhibited no mutagenicity. Administration of black soybeans to mice showed no effects on food intake and body and organ weights. The nanonized black soybean group had a lower degree of spontaneous fatty liver, alanine aminotransferase, and thiobarbituric acid-reactive substance concentrations, and had enhanced superoxide dismutase, catalase, and glutathione peroxidase activities of livers when compared with the SAMP8 control and micronized black soybean groups. The mice fed with black soybeans had significantly lower triglyceride concentrations than the SAMP8 control group. The results of this study suggest that nanonized black soybeans have no side effects and, moreover, may minimize liver lesions in SAMP8 mice.

Dorsomedial medulla is more susceptible than rostral ventrolateral medulla to hypoxic insult in cats.

We investigated the responses of systemic arterial pressure and vertebral sympathetic nerve activity to glutamate microinjections (0. 1 M, 70 nl) in the dorsomedial (DM) and the rostral ventrolateral medulla (RVLM) before hypoxia and after reoxygenation (posthypoxia) after various degrees of hypoxia in anesthetized cats. Hypoxia was produced by ventilating 5% O(2) and 95% N(2) for different durations (hypoxia I-III). In intact cats, the glutamate-induced systemic arterial pressure and vertebral nerve activity responses of the DM were depressed after all degrees of hypoxia. Posthypoxic depression in the RVLM, however, was not observed until hypoxia II and III. Precollicular decerebration prevented depression in the RVLM, but, for the DM, it was effective only for hypoxia I. Baro- and chemoreceptor denervation abolished all posthypoxic depression in both the DM and the RVLM. Pressor responses to tyramine (100-400 microg/kg iv) remained unchanged after all degrees of hypoxia. These results suggest that the DM is more susceptible to hypoxia than the RVLM. The peripheral baro- and chemoreceptors and the suprapontine structures apparently play an important role in posthypoxic depression. Moreover, the depression is not due to the postganglionic norepinephrine depletion.