Thyroid structure, function and iodine status by pregnancy trimester in Harbin, China.

BACKGROUND AND OBJECTIVES: Thyroid disease in pregnancy can have devastating effect on the fetus. In Harbin, China, there is insufficient knowledge about the incidence of and contributing factors to thyroid disease in pregnancy. This study investigates whether urine iodine concentration (UIC), as a proxy for iodine intake, affects the thyroid structure and/or function during each trimester. METHODS AND STUDY DESIGN: Data of 24000 pre-pregnant women were collected from January 2017 to August 2019. Serum thyroid hormone levels were measured, and thyroid ultrasonography was performed. If thyroid ultrasonography and thyroid function findings were normal before pregnancy and were abnormal after pregnancy, the current gestational age was recorded and the UIC was measured. Finally, a total of 500 participants were included in the study. RESULTS: There were significant differences in the incidence of abnormal thyroid structure and function between trimester groups (p<0.05). Thyroid nodular lesions were the most common abnormal ultrasound finding, and positive thyroid peroxide antibodies (TPOAb) were the most common abnormal thyroid function test results. There were significant differences in the median UIC between trimester groups (p<0.001); the median UIC decreased with increasing gestational age. The incidence of abnormal thyroid structure or function was not significantly different across UIC groups (p>0.05). CONCLUSIONS: In women from Harbin, thyroid structural or functional abnormalities commonly occur in the second and third trimesters of pregnancy. Thyroid nodular lesions and positive TPOAb are the commonest thyroid abnormalities. The median UIC significantly declines with increasing gestational age. Pregnant women in Harbin have iodine-deficient states.

Urine iodine level and multiple risks are associated with thyroid structural abnormalities among adults in Heilongjiang Province, China.

BACKGROUND AND OBJECTIVES: The prevalence of adult thyroid structural abnormalities has increased significantly worldwide. However, no study has examined the thyroid structure and urine iodine levels of adults in Heilongjiang Province in the last decade. Therefore, this study aims to investigate the rate and risk factors of thyroid structural abnormalities among the residents of this province. METHODS AND STUDY DESIGN: A probability proportional sampling method was used, and a total of 3,645 individuals in Heilongjiang Province were included. The subjects was asked to complete a thyroid ultrasound and fill out a questionnaire. Furthermore, urine iodine levels and salt iodine content were determined, and multivariate logistic regression was used to identify the independent risk factors for thyroid diseases. RESULTS: The prevalence of thyroid structural abnormalities in Heilongjiang Province was 56.0%. Univariate analysis showed that there were significant differences between the structural abnormalities group and the normal thyroid group in terms of sex, age, body mass index, hypertension, diabetes, smoking, alcohol consumption, frequency of seafood consumption and pickled food consumption, employment status, and urine iodine level (p<0.05). Multivariate analysis showed that the following were independent risk factors of thyroid disease: female, increased age, hypertension, diabetes, cigarette smoking frequent seafood consumption, employment, and urine iodine levels. CONCLUSIONS: The prevalence of thyroid structural abnormalities in adults in Heilongjiang Province was relatively high. Therefore, to help prevent the occurrence of thyroid disease in adults in Heilongjiang Province, the risk factors of thyroid structural abnormalities should be better understood.

Plasma preptin levels are decreased in patients with essential hypertension.

The pancreatic hormone preptin amplifies glucose-mediated insulin secretion, and we investigated its circulating levels in patients with essential hypertension and possible association with carotid atherosclerosis. Ninety-eight patients were divided into hypertensive and control groups. Relationships between plasma preptin levels, clinical parameters, and carotid artery intima-media thickness (IMT) were analyzed. Plasma preptin levels were significantly lower in the hypertensive group than in the control group (1930.30±268.47 vs. 2182.88±325.81 pg/mL, P < 0.01). Simple linear regression analysis showed that systolic blood pressure (SBP), mean arterial pressure (MAP), and levels of serum low-density lipoprotein (LDL) and cholesterol (CHOL) were related to plasma preptin levels. Furthermore, multivariate linear regression analysis showed that SBP and serum CHOL levels were independent of plasma preptin levels, which were inversely correlated with carotid artery IMT (r = -0.47, P < 0.01) in all subjects. Plasma preptin levels of patients with carotid atherosclerotic plaques were significantly lower than those of patients without plaques (1961.69±296.07 vs. 2117.97±322.52 pg/mL, P < 0.05). This preliminary study revealed that plasma preptin levels are decreased in patients with essential hypertension, negatively correlated with carotid artery IMT, and significantly lower in patients with carotid atherosclerotic plaques. Therefore, decreased plasma preptin level might play a role in hypertension and its vascular complications.

Cortistatin Inhibits NLRP3 Inflammasome Activation of Cardiac Fibroblasts During Sepsis.

BACKGROUND: Cortistatin is a recently discovered neuropeptide that has emerged as a potential endogenous antiinflammatory peptide. As a clinical syndrome, sepsis occurs when an infection becomes amplified, leading to organ dysfunction or risk for secondary infection. Human septic shock involves excessive inflammatory cytokine production. Interleukin (IL) 1ß is one of these cytokines, and it plays a pivotal role in sepsis-induced myocardial dysfunction. The aim of the present study is to evaluate whether cortistatin inhibits nucleotide-binding oligomerization domain-like receptor with a pyrin-domain 3 (NLRP3) inflammasome/caspase-1/IL-1ß pathway in cardiac fibroblasts (CFs) and whether this role can subsequently affect myocardial injury. METHODS AND RESULTS: To test these processes, a murine model of cecal ligation and puncture in vivo and lipopolysaccharide-induced cardiac fibroblasts were used in vitro. We found that pretreatment with cortistatin inhibited NLRP3-mediated ASC pyroptosome formation, caspase-1 activation, and IL-1ß secretion. Additionally cortistatin inhibits proinflammatory pathways (nuclear factor κB and pro-IL-1ß). CONCLUSIONS: This work provided the first evidence of cortistatin as a new immunomodulatory factor with the capacity to deactivate NLRP3 inflammasome activity and to protect against the myocardial injury induced by sepsis. This study has important implications for the design of new strategies to control NLRP3-related diseases.

Correlation between ovarian chocolate cyst and serum carbohydrate antigen 125 level and the effect of ultrasound-guided interventional sclerotherapy on serum carbohydrate antigen 125 level.

AIM: This study was to investigate the correlation between ovarian chocolate cysts and serum carbohydrate antigen (CA)-125 levels and to demonstrate the effect of ultrasound-guided interventional sclerotherapy (UGIS) on serum CA-125 levels. METHODS: Based on the serum CA-125 level, as determined by chemiluminescence detection prior to UGIS, 105 patients with ovarian chocolate cysts were divided into the normal group (CA-125 ≤ 35 U/mL, 45 patients) and the abnormal group (35 U/mL < CA-125 ≤ 200 U/mL, 60 patients). There were six clinical indicators including age, disease duration, dysmenorrhea history, child-bearing history, abortion history and surgical history. The ultrasonography characteristics were cyst diameter, cyst wall thickness and the side on which the cyst occurred. The correlations between serum CA-125 levels pretreatment and the clinical indicators and ultrasonography characteristics was analyzed. The serum CA-125 levels pretreatment, 3 months post-treatment and 6 months post-treatment were compared. RESULTS: The pretreatment serum CA-125 levels of the 105 patients positively correlated with disease duration (r = 0.3932, P = 0.0040), dysmenorrhea history (r = 0.2351, P = 0.0111), cyst diameter (r = 0.3415, P < 0.0001) and cyst wall thickness (r = 0.4263, P < 0.0001). Compared with the pretreatment level, the mean serum CA-125 level in the abnormal group at 3 months post-treatment was significantly lower (P < 0.01), and at 6 months post-treatment, the mean serum CA-125 level had decreased to a normal level (P < 0.01). CONCLUSION: UGIS significantly decreased abnormal serum CA-125 levels in patients with ovarian chocolate cysts.

Metformin protects the myocardium against isoproterenol-induced injury in rats through alleviating endoplasmic reticulum stress.

Clinical studies have suggested that metformin, a widely used antidiabetic agent, exerts a direct cardioprotective effect on cardiovascular disease in addition to its blood glucose-lowering activity. This study was designed to identify the role of metformin in rats with isoproterenol (ISO)-induced myocardial injury and to investigate its underlying mechanism. A rat model of myocardial ischemic injury was established by the subcutaneous injection of a high dose of ISO, a beta-adrenergic agonist. The results showed that pretreatment of metformin significantly reduced rat mortality induced by ISO, attenuated the increased plasma lactate dehydrogenase activity and myocardium malondialdehyde level, alleviated the hemodynamic disturbance, inhibited the upregulated gene expression of myocardial probrain natriuretic peptide and alleviated the myocardial morphological injury and apoptosis induced by ISO. Furthermore, western blot analysis showed that metformin suppressed the overexpression of the endoplasmic reticulum stress (ERS) markers cleaved caspase-12 and CEBP-homologous protein induced by ISO and increased the phosphorylation of AMP-activated protein kinase (AMPK). In conclusion, these data suggest that metformin might protect the myocardium against acute ischemic injury in rats at least partially by activating AMPK and alleviating aberrant ERS. These findings might provide further experimental evidence for treating patients at risk of ischemic heart disease with metformin.

Ghrelin inhibited pressure overload-induced cardiac hypertrophy by promoting autophagy via CaMKK/AMPK signaling pathway.

Ghrelin, a novel gut hormone, has been shown to exert protective effects on cardiac dysfunction and remodeling. However, the underlying mechanisms of its protective effects remain unclear. Here, we investigated the effects of ghrelin on cardiac hypertrophy and explored the mechanisms involved. Ghrelin (30 µg.kg-1. day-1) was systemically administered to rats with cardiac hypertrophy induced by abdominal aortic constriction (AAC) by a mini-osmotic pump the next day after surgery continuously for 4 weeks. The AAC treated rats without ghrelin infusion showed decreased ghrelin content and expression of its receptors in the hearts. Exogenous ghrelin greatly attenuated cardiac hypertrophy as shown by heart weight to tibial length (HW/TL), hemodynamics, echocardiography, histological analyses, and expression of hypertrophic markers induced by AAC. This corresponded with decreased cardiac fibrosis and inflammation in the hearts of AAC rats treated with ghrelin. Moreover, ghrelin significantly increased the myocardial expression of autophagy markers, which was further confirmed in cultured cardiomyocytes. Concurrently, cardiomyocyte apoptosis in vivo and in vitro was ameliorated by ghrelin, which was reversed by inhibition of autophagy. The enhancement of autophagy and inhibition of apoptosis by ghrelin were eliminated on pretreatment with compound C, an AMP-activated protein kinase (AMPK) inhibitor. Furthermore, inhibition of Ca2+/Calmodulin-dependent protein kinase kinase (CaMKK), an upstream kinase of AMPK, made ghrelin fail to activate AMPK and simultaneously reversed ghrelin's promotion of autophagy. In conclusion, ghrelin could exert its cardioprotective effects on cardiac hypertrophy by promoting autophagy, possibly via CaMKK/AMPK signaling pathway.

Expression of the NEK7/NLRP3 inflammasome pathway in patients with diabetic lower extremity arterial disease.

INTRODUCTION: The NLRP3 inflammasome is closely related to diabetes and atherosclerosis. Recent studies suggest NIMA-related kinase 7 (NEK7) is necessary for NLRP3 inflammasome activation during potassium efflux. However, the expression of the NEK7/NLRP3 inflammasome pathway in diabetic lower extremity arterial disease (DLEAD) is unclear. The present study aimed to explore whether the NEK7/NLRP3 inflammasome pathway is involved in the pathogenesis of DLEAD. RESEARCH DESIGN AND METHODS: The serum levels of interleukin-1ß (IL-1ß) and IL-18 in the control group (n=39), diabetes without lower extremity artery diseases group (n=39) and DLEAD group (n=85) were measured. H&E and Von Kossa staining were used to observe the vasculature of amputated feet from patients with diabetic foot. Furthermore, immunohistochemical staining, immunofluorescence and western blot were used to detect the expression of NEK7 and the NLRP3 inflammasome. RESULTS: The serum IL-1ß level in the DLEAD group was significantly increased compared with that in the control group and diabetes without lower extremity artery disease group. The serum IL-18 level was significantly higher in the DLEAD group and diabetes without lower extremity artery disease group than in the control group. H&E staining showed that the subintimal tissue of the arteries of patients with diabetic foot were highly thickened and exhibited irregular atherosclerotic plaques, and the arterial lumen was nearly occluded. Von Kossa staining showed dense brown-black calcium salt deposits in the vascular mesangium. Moreover, the expression of NEK7 and the NLRP3 inflammasome was significantly increased in the vascular cells of patients with diabetic foot, especially in vascular smooth muscle cells. CONCLUSION: The NEK7/NLRP3 inflammasome pathway might be involved in the pathogenesis of DLEAD.

Ginsenoside Rg3 protects heart against isoproterenol-induced myocardial infarction by activating AMPK mediated autophagy.

BACKGROUND: Panax ginseng is a well-known medicinal herb that is widely used in traditional Chinese medicine for treating various diseases. Ginsenoside Rg3 (Rg3) is thought to be one of the most important active ingredients of Panax ginseng. However, the molecular mechanism underlying the beneficial effects of Rg3 has been elusive. METHODS: In the mouse heart injury model induced by isoproterenol (ISO), we used brain natriuretic peptide (BNP), lactate dehydrogenase (LDH) and caspase-3 ELISA kits to test myocardium injury. To test whether Rg3 protects myocardial injury through AMPK mediated autophagy, we used specific AMPK inhibitor in combination with Rg3. NLRP3 inflammasome related molecules such as NLRP3, ASC and caspase-1 were measured by western-blot following Rg3 treatment. RESULTS: We found that Rg3 significantly reduced ISO induced myocardial injury indicated by the downregulation of serum BNP and LDH. In addition, we showed that the improvement of myocardial injury by Rg3 was associated with enhanced expression of autophagy related protein and activation of AMPK downstream signaling pathway. CONCLUSIONS: We observed that inhibition of AMPK significantly reversed the myocardial protective effect of Rg3, which is associated with a decrease of Rg3 induced autophagy. These together suggested that Rg3 may improve myocardial injury during MI through AMPK mediated autophagy. Our study also provides important translational evidence for using Rg3 in treating myocardial infarction (MI).

Differentially expressed gene profiles in the serum before and after the ultrasound-guided ethanol sclerotherapy in patients with ovarian endometriomas.

OBJECTIVES: To detect the differentially expressed genes and subsequently identify disease-related signatures and potential biomarkers for patients with ovarian endometriomas in the serum before and after the ultrasound-guided ethanol sclerotherapy in patients with ovarian endometriomas. DESIGN AND METHODS: Venous blood samples were collected from nine patients with ovarian endometriomas before and after ultrasound-guided ethanol sclerotherapy, and the serum were isolated after centrifugation. NimbleGen human gene expression microarrays analysis was conducted to analyse gene ontology categories (GO terms) and signalling pathways of differentially expressed genes. The accuracy of some typical genes from microarray analysis was verified by quantitative PCR (qPCR). RESULTS: Approximately 45,033 genes were analysed by NimbleGen human gene expression microarrays, which identified 447 genes that showed differential expressions before and after therapy. Of these, 225 genes were up-regulated and 222 genes were down-regulated. The GO terms of the down-regulated genes were strongly associated with the pathogenesis of ovarian endometriomas; 15 down-regulated genes showed overlaps in both signalling pathways and GO terms. Among these, six genes showed statistical significance including IL6, CD36, JUNB, B4GALT1, HES1, and NR4A1, which were also validated by qPCR analysis. CONCLUSIONS: There were differentially expressed genes in the serum before and after ultrasound-guided ethanol sclerotherapy in patients with ovarian endometriomas. Notably, the expressions of IL6, CD36, JUNB, B4GALT1, HES1, and NR4A1, which are strongly associated with the pathogenesis of ovarian endometriomas, were significantly down-regulated after ethanol sclerotherapy. This may not only help us understand EMs pathogenesis, but also provide potential biomarkers for verifying the effects of ethanol sclerotherapy.

Ghrelin protects heart against ERS-induced injury and apoptosis by activating AMP-activated protein kinase.

Ghrelin, the endogenous ligand of growth hormone secretagogue receptor (GHS-R), is a cardioprotective peptide. In our previous work, we have revealed that ghrelin could protect heart against ischemia/reperfusion (I/R) injury by inhibiting endoplasmic reticulum stress (ERS), which contributes to many heart diseases. In current study, using both in vivo and in vitro models, we investigated how ghrelin inhibits myocardial ERS. In the in vivo rat heart injury model induced by isoproterenol (ISO), we found that exogenous ghrelin could alleviate heart dysfunction, reduce myocardial injury and apoptosis and inhibit the excessive myocardial ERS induced by ISO. More importantly, the activation of AMP-activated protein kinase (AMPK) was observed. To explore the role of AMPK activation in ERS inhibition by ghrelin, we set up two in vitro ERS models by exposing cultured rat cardiomyocytes to tunicamycin(Tm) or dithiothreitol (DTT). In both models, compared with Tm or DTT treatment alone, pre-incubation cardiomyocytes with ghrelin significantly activated AMPK, reversed the upregulation of the ERS markers, C/EBP-homologous protein (CHOP) and cleaved caspase-12, and reduced apoptosis of cardiomyocytes. Further, we found that the ERS inhibitory and anti-apoptotic actions induced by ghrelin were blocked by an AMPK inhibitor. To investigate how ghrelin activates AMPK, selective antagonist of GHS-R1a and inhibitor of Ca(2+)/Calmodulin-dependent protein kinase kinase (CaMKK) were added, respectively, before ghrelin pre-incubation, and we found that AMPK activation was prevented and the ERS inhibitory and anti-apoptotic actions of ghrelin were blocked. In conclusion, ghrelin could protect heart against ERS-induced injury and apoptosis, at least partially through a GHS-R1a/CaMKK/AMPK pathway.