Bioactive Hormone Research Articles

Plasma concentrations of peptide hormones: Unrealistic levels of vasopressin (AVP), oxytocin (OXT), and brain natriuretic peptide (BNP).

Hormones are specific molecules measured in biological fluids by elaborate analytical systems requiring meticulous attention. Variation between laboratories can be expected. However, recently published measurements of AVP, OXT, and BNP in human plasma under basal/control conditions include numbers which, between publications, vary by 100-10 000-fold. Generally, the methods descriptions are scant, at best, and provide no information about quality control measures. Clearly, two results describing the same basal hormone concentration by numbers three orders of magnitude apart are incongruent providing reason for concern. Basal concentrations of bioactive AVP, OXT, and BNP in human plasma are in the order of 1-10 pmol/L. Therefore, assay systems applied to plasma must be able to measure concentrations of less than 1 pmol/L with appropriate specificity and accuracy. Basal concentrations of AVP, OXT, and BNP above 100 pmol/L should be reconsidered, as such results do not reflect bioactive hormone levels in humans, rats, or mice. Any concentration above 1000 pmol/L is of concern because such levels of bioactive hormone may be seen only under extreme conditions, if at all.

A gibberellin-assisted study of the transcriptional and hormonal changes occurring at floral transition in peach buds (Prunus persica L. Batsch)

BackgroundFlower load in peach is an important determinant of final fruit quality and is subjected to cost-effective agronomical practices, such as the thinning, to finely balance the sink-source relationships within the tree and drive the optimal amount of assimilates to the fruits. Floral transition in peach buds occurs as a result of the integration of specific environmental signals, such as light and temperature, into the endogenous pathways that induce the meristem to pass from vegetative to reproductive growth. The cross talk and integration of the different players, such as the genes and the hormones, are still partially unknown. In the present research, transcriptomics and hormone profiling were applied on bud samples at different developmental stages. A gibberellin treatment was used as a tool to identify the different phases of floral transition and characterize the bud sensitivity to gibberellins in terms of inhibition of floral transition.ResultsTreatments with gibberellins showed different efficacies and pointed out a timeframe of maximum inhibition of floral transition in peach buds. Contextually, APETALA1 gene expression was shown to be a reliable marker of gibberellin efficacy in controlling this process. RNA-Seq transcriptomic analyses allowed to identify specific genes dealing with ROS, cell cycle, T6P, floral induction control and other processes, which are correlated with the bud sensitivity to gibberellins and possibly involved in bud development during its transition to the reproductive stage. Transcriptomic data integrated with the quantification of the main bioactive hormones in the bud allowed to identify the main hormonal regulators of floral transition in peach, with a pivotal role played by endogenous gibberellins and cytokinins.ConclusionsThe peach bud undergoes different levels of receptivity to gibberellin inhibition. The stage with maximum responsiveness corresponded to a transcriptional and hormonal crossroad, involving both flowering inhibitors and inductors. Endogenous gibberellin levels increased only at the latest developmental stage, when floral transition was already partially achieved, and the bud was less sensitive to exogenous treatments. A physiological model summarizes the main findings and suggests new research ideas to improve our knowledge about floral transition in peach.

Adipokine Modulation in Endometrial Hyperplasia by Polyunsaturated Fatty Acids

Background Obesity is associated with a higher prevalence of endometrial hyperplasia, thereby increasing the risk of endometrial and ovarian cancers. The precise mechanisms linking obesity to endometrial hyperplasia remain unclear, but dysregulation of adipose tissue homeostasis is known to play a significant role. Hypertrophied adipocytes in obese individuals secrete various bioactive substances, including cytokines, growth factors, hormones, and metabolites. Additionally, hyperplastic adipocytes exhibit enhanced aromatase activity, leading to increased estrogen synthesis, which further promotes the development of endometrial hyperplasia. Purpose The purpose of this study is to explore the anti-inflammatory and anti-proliferative activities of the poly unsaturated fatty acids. Methodology An extensive literature survey has been performed to identify the role of adipokines and elevated endogenous estrogen levels in activating cell survival signaling pathways, such as PI3K/Akt/mTOR, MEK/ERK1, and JAK–STAT in endometrial cells and their possible role in Endometrial Hyperplasia. Further, the possible beneficial anti-inflammatory and anti-proliferative effects of polyunsaturated fatty acids (PUFAs) such as eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and arachidonic acid (AA) were explored. Results Numerous studies suggest the beneficial role of dietary fats, such as EPA, DHA, and AA in modulating the growth of endometrium in obesity-induced endometrial hyperplasia. PUFAs can activate adenosine monophosphate-activated protein kinase (AMPK), which inhibits gluconeogenesis and lipogenesis. It also phosphorylates acetyl-CoA, leading to a decrease in malonyl-CoA, which inhibits mitochondrial CPT1. Additionally, AMPK activation promotes β-oxidation, and PPAR-γ mechanisms by down regulating the NF-kB pathway involved in endometrial hyperplasia. Conclusion This review sheds light on the potential of PUFAs in mitigating estrogen synthesis, adipokine secretion, and endogenous aromatase activity in obesity induced endometrial hyperplasia. Furthermore, it critically evaluates the role and mechanisms of PUFAs in attenuating obesity-associated endometrial hyperplasia and reducing the risk of ovarian cancer.

Establishment of a novel weight reduction model after laparoscopic sleeve gastrectomy based on abdominal fat area.

In light of ongoing research elucidating the intricacies of obesity and metabolic syndrome, the role of abdominal fat (especially visceral fat) has been particularly prominent. Studies have revealed that visceral adipose tissue can accelerate the development of metabolic syndrome by releasing various bioactive compounds and hormones, such as lipocalin, leptin and interleukin. A retrospective analysis was performed on the clinical data of 167 patients with obesity. Among them, 105 patients who satisfied predefined inclusion and exclusion criteria were included. The parameters evaluated included total abdominal fat area (TAFA), laboratory indicators and anthropometric measurements. Weight reduction was quantified through percent total weight loss (%TWL) and percent excess weight loss (%EWL) postoperatively. Binary logistic regression analysis and receiver operating characteristic (ROC) curve analysis were employed to identify predictors of weight loss. Binary logistic regression analysis emphasized that total abdominal fat area was an independent predictor of %EWL ≥75% (p < 0.001). Total abdominal fat area (p = 0.033) and BMI (p = 0.003) were independent predictors of %TWL ≥30%. In our cohort, %TWL ≥30% at 1 year after surgery was closely related to the abdominal fat area and BMI. Based on these results, we formulated a novel model based on these factors, exhibiting superior predictive value for excellent weight loss.

Phenotype Transformation of PitNETs.

Phenotype transformation in pituitary neuroendocrine tumors is a little-known and unpredictable clinical phenomenon. Previous studies have not clearly defined and systematically concluded on the causes of this rare phenomenon. Additionally, the mechanisms of phenotype transformation are not well known. We reviewed cases reported in the literature with the aim of defining phenotype transformation in pituitary neuroendocrine tumors. We present an overview of the wide spectrum of phenotype transformation and its clinical features. We also discuss findings on the potential mechanism of this rare transformation, which may be related to PC1/3, the bioactivity of secretory hormones, gene mutations and the plasticity of pituitary neuroendocrine tumors. Clinicians should be aware of this rare phenomenon and more studies on the underlying mechanisms are required.

Characterization of Phytaspase Proteolytic Activity Using Fluorogenic Peptide Substrates.

Within the subtilase family of plant proteolytic enzymes, phytaspases are distinguished by their strict substrate cleavage specificity after an aspartate residue preceded by a characteristic tripeptide amino acid motif. This type of recognition resembles that of animal apoptotic proteases, caspases. Phytaspases attract attention not only because they are critically important for the accomplishment of stress-induced death of plant cells, but also due to their ability to specifically process precursor proteins, thus generating bioactive plant peptide hormones, systemin and phytosulfokine. As the activity of phytaspases appears to be essential for life and death decisions made by the plant cell, elaboration of an approach to characterize and quantitate phytaspase proteolytic activity is of importance. Here we provide a protocol for phytaspase activity determination and characterization using fluorogenic peptide substrates. This approach works well, both with purified phytaspase samples, and with crude extracts from plant tissues. We also discuss advantages of the assay, factors that may influence its sensitivity and specificity, as well as possible pitfalls.

Ambulatory blood pressure monitorisation in children with recombinant growth hormone treatment.

It is safe to use recombinant growth hormone in children. Studies have shown it to be effective and safe, except for a few side effects in the short and long term after treatment. The present study investigated the presence of hypertension in pediatric patients receiving growth hormone treatment using 24 h ambulatory blood pressure monitoring (ABPM). This study is a single-center, retrospective study. Eighty-four patients aged 5-16 years who received growth hormone treatment for at least 3months, who underwent 24 h ABPM were analyzed. They were compared with 67 patients who had no risk factors for hypertension. In the study, 84 rhGH-treated patients (45.2 % male, 54.8 % female) and 67 healthy control groups (49.3 % male, 50.7 % female) were analyzed. The mean age of the patient group was 10.83±2.85 years and the mean age of the healthy control group was 13.1±2.93 years. The diagnostic classification of the patients receiving treatment was as follows: 66.6 % (n=56) partial growth hormone deficiency, 22.6 % (n=19) growth hormone deficiency, 7.1 % (n=6) bioactive growth hormone, 2.3 % (n=2) idiopathic short stature, 1.1 % (n=1) low birth weight for gestational age (SGA). Body mass index was significantly lower in the treated group (p=0.013). The duration of treatment was 6.04±4.9months. Daytime diastolic blood pressure was significantly lower in the treated group (p=0.001). There was no correlation between BMI and ABPM parameters in the treatment group and the control group. The present study shows that growth hormone treatment is safe in terms of high blood pressure.

Hybrid Functional Polymer-Enabled Multiplexed Chemosensor Patch for Wearable Adrenocortex Stress Profiling.

Measuring bioactive stress hormones, including cortisol and dehydroepiandrosterone (DHEA), allows for evaluating the hypothalamic-pituitary-adrenal (HPA) axis functioning, offering valuable insights into an individual's stress response through adrenocortex stress profiles (ASPs). Conventional methods for detecting steroid hormones involve sample collections and competitive immunoassays, which suffer from drawbacks such as time-consuming labeling and binding procedures, reliance on unstable biological receptors, and the need for sophisticated instruments. Here, we report a label-free and external redox reagent-free amperometric assay directly detecting sweat cortisol and DHEA levels on the skin. The approach utilizes multitarget sensors based on redox-active molecularly imprinted polymers (redox MIPs) capable of selectively binding cortisol and DHEA, inducing changes in electrochemical redox features. The redox MIP consists of imprinted cavities for specific capture of cortisol or DHEA in a poly(pyrrole-co-(dimethylamino)pyrrole) copolymer containing hydrophobic moieties to enhance affinity toward steroid hormones. The polymer matrix also incorporates covalently linked interpenetrating redox-active polyvinylferrocene, offering a stable electrochemical redox feature that enables sensitive current change in response to the target capture in the vicinity. The multiplexed sensor detects cortisol and DHEA within 5 min, with detection limits of 115 and 390 pM, respectively. Through the integration of redox MIP sensors into a wireless wearable sensing system, we successfully achieved ambulatory detection of these two steroid hormones in sweat directly on the skin. The new sensing method facilitates rapid, robust determination of the cortisol-DHEA ratio, providing a promising avenue for point-of-care assessment of an individual's physiological state.

Application of machine learning algorithms to predict lymph node metastasis in gastric neuroendocrine neoplasms

BackgroundNeuroendocrine neoplasms (NENs) are tumors that originate from secretory cells of the diffuse endocrine system and typically produce bioactive amines or peptide hormones. This paper describes the development and validation of a predictive model of the risk of lymph node metastasis among gastric NEN patients based on machine learning platform. MethodsIn this investigation, data from 1256 patients were used, of whom 119 patients from the First Affiliated Hospital of Soochow University in China and 1137 cases from the surveillance epidemiology and end results (SEER) database were combined. Six machine learning algorithms, including the logistic regression model (LR), random forest (RF), decision tree (DT), Naive Bayes (NB), support vector machine (SVM), and k-nearest neighbor algorithm (KNN), were used to build the predictive model. The performance of the models was evaluated using the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity. ResultsAmong the 1256 patients with gastric NENs, 276 patients (21.97 %) developed lymph node metastasis. T stage, tumor size, degree of differentiation, and sex were predictive factors of lymph node metastasis. The RF model achieved the best predictive performance among the six machine learning models, with an AUC, accuracy, sensitivity, and specificity of 0.81, 0.78, 0.76, and 0.82, respectively. ConclusionThe RF model provided the best prediction and can help physicians determine the lymph node metastasis risk of gastric NEN patients to formulate individualized medical strategies.

Exogenous corticosterone administration during pregnancy in mice alters placental and fetal thyroid hormone availability in females

IntroductionMaternal prenatal psychological stress is associated with adverse pregnancy outcomes and increased risk of adverse health outcomes in children. While the molecular mechanisms that govern these associations has not been fully teased apart, stress-induced changes in placental function can drive sex-specific phenotypes in offspring. We sought to identify and examine molecular pathways in the placenta that are altered in response to maternal prenatal stress. MethodsWe previously employed a mouse model of maternal prenatal stress where pregnant dams were treated with stress hormone (CORT) beginning in mid-gestation. Using this model, we conducted RNAseq analysis of whole placenta at E18.5. We used qRT-PCR to validate gene expression changes in the placenta and in a trophoblast cell line. ELISAs were used to measure the abundance of thyroid hormones in maternal and fetal serum and in the placenta. ResultsDio2 was amongst the top differentially expressed genes in response to exogenous stress hormone. Dio2 expression was more downregulated in placenta of female fetuses from CORT-treated dams than both control placenta from females and placenta from male fetuses. Consistent with Dio2's role in production of bioactive thyroid hormone (T3), we found that there was a reduction of T3 in placenta and serum of female embryos from CORT-treated dams at E18.5. Both T3 and T4 were reduced in the fetal compartment of the placenta of female fetuses from CORT-treated dams at E16.5. Exogenous stress hormone induced reduction in thyroid hormone in females was independent of circulating levels of TH in the dams. DiscussionThe placental thyroid hormone synthesis pathway may be a target of elevated maternal stress hormone and modulate fetal programming of health and disease of offspring in a sex-specific fashion.

A novel hepcidin mutation.

The bioactive peptide hormone hepcidin-25 regulates iron levels by inhibiting iron transport to plasma via ferroportin. Hepcidin-25 is synthesized in the liver where the 84 amino acids pro-hepcidin is cleaved into the bioactive hepcidin-25. A patient admitted to the hospital presented with infertility and fatigue. Genomic DNA was purified from whole blood using the Maxwell 16 system (Promega). MLPA analysis was performed to detect large genomic rearrangements using the SALSA MLPA kit # P347, Hemochromatosis (MRC Holland, Holland). Plasma hepcidin measurements were performed using liquid chromatography/tandem mass spectrometry (LC-MS/MS). A novel HAMP mutation (homozygous one base deletion in c.215delG, p.Cys72Serfs*?) was detected. The deletion in nucleotide 215 causes a frameshift altering the predicted protein sequence from cysteine13 in mature peptide. Whether this leads to nonsense mediated decay of the mRNA or synthesis of an aberrant peptide in unknown, but bioactive hepcidin-25 was undetectable in plasma. The patient had massive iron overload with ferritin up to 8360µg/L. He was anaemic with a Hb at 7.0mmol/L (11.3g/dL) and suffered from hypogonadotropic hypogonadism with a total testosterone of 1.2nmol/l. Continued treatment with venesection and gonadotropins led to reduced fatigue, reduction in iron overload, a normalized Hb and improvement of semen quality. A novel hepcidin mutation was detected in a patient with massive iron overload, fatigue and hypogonadotropic hypogonadism.

Effect of High Hydrostatic Pressure Processing and Holder Pasteurization of Human Milk on Inactivation of Human Coronavirus 229E and Hepatitis E Virus.

In preterm infants, sterilized donor milk (DM) is frequently used for feeding when breast milk is lacking. Most human milk banks use the Holder pasteurization method (HoP) to ensure the microbiological safety of DM. However, this method degrades many bioactive factors and hormones. Recently, high hydrostatic pressure (HHP) processing, which preserves bioactive factors in human milk, has been proposed as an alternative method to ensure the safety of DM. Although HHP treatment has been shown to be effective for viral inactivation, the effect of HHP on viruses that may be present in the complex nutritional matrix of human milk has not yet been defined. In the present study, we compared the efficacy of two HHP protocols (4 cycles at 350 MPa at 38 °C designated as 4xHP350 treatment, and 1 cycle at 600 MPa at 20 °C designated as 1xHP600 treatment) with the HoP method on artificially virus-infected DM. For this purpose, we used human coronavirus 229E (HCoV-229E) and hepatitis E virus (HEV) as surrogate models for enveloped and non-enveloped viruses. Our results showed that HCoV-229E is inactivated by HHP and HoP treatment. In particular, the 4xHP350 protocol is highly effective in inactivating HCoV-229E. However, our results demonstrated a matrix effect of human milk on HCoV-229E inactivation. Furthermore, we demonstrated that HEV is stable to moderate pressure HHP treatment, but the milk matrix does not protect it from inactivation by the high-pressure HHP treatment of 600 MPa. Importantly, the complex nutritional matrix of human milk protects HEV from inactivation by HoP treatment. In conclusion, we demonstrated that HHP and HoP treatments do not lead to complete inactivation of both surrogate virus models, indicating that these treatments cannot guarantee total viral safety of donor milk.

Exploring bioactive compounds from a symbiotic bacterial strain of Spongiobacter sp.

Marine sponges are a host of different symbiotic groups of bacteria playing crucial roles in the protection and survival of marine sponges. Marine symbiotic bacteria from sponges are promising sources of bioactive chemicals and are increasingly being investigated. Therefore, the present study was undertaken to analyze total compounds from active symbiotic bacterial strain from sponge, Pione vastifical. Potential bacterial strain EA276 previously isolated from P. vastifical and was identified as Spongiobacter sp. Among 57 isolates, only 42% exhibited antagonistic activity. Four major classes of bacteria were reported previously where γ-Proteobacteria, was the dominant class. From these active antagonistic bacterial isolates, a potential bacterial strain Spongiobacter sp. EA276 was selected, and total metabolites were identified using GC and LC-MS analyses. Using LC-MS analysis bioactive compounds Dichlorphenamide, Amifloxacin and Carbenicillin are identified in both positive and negative mode. Plant growth hormones, Indole-3-acetic acid and Methyl jasmonate were identified using GC-MS analysis from culture extract of strain Spongiobacter sp. EA276. Our results highlighted the significance of marine flora inhabiting sponges from the Red Sea as potential source of bioactive compounds and plant growth hormones of biological and agricultural significance.

Role of hepatic deiodinases in thyroid hormone homeostasis and liver metabolism, inflammation, and fibrosis.

Thyroid hormones play an essential role in regulating whole-body homeostasis. Deiodinases are known to convert thyroid hormone from the prohormone thyroxine (T4) to the bioactive hormone tri-iodothyronine (T3) and convert both T4 and T3 toward their inactive metabolites 3,3',5'-tri-iodothyronine (rT3) and 3,3'-di-iodothyronine (3,3'-T2). Deiodinases are thus important for the regulation of intracellular thyroid hormone concentrations. This is known to be crucial both during development and adult life in regulating thyroid hormone-related gene transcription. This review discusses the importance of liver deiodinases in determining serum and liver thyroid hormone concentrations, liver metabolism and liver disease.

Hepatocyte-derived DPP4 regulates portal GLP-1 bioactivity, glucose production, and its absence alters liver disease progression.

Elevated circulating dipeptidyl-peptidase 4 is a biomarker for liver disease, but its involvement in gluconeogenesis and in metabolic-associated fatty liver disease (MAFLD) progression remains unclear. Here we identified that DPP4 in hepatocytes but not Tie2+ endothelial cells regulates the local bioactivity of incretin hormones and gluconeogenesis. However, the complete absence of DPP4 (Dpp4-/-) in aged mice with metabolic syndrome accelerates liver fibrosis without altering dyslipidemia and steatosis. Analysis of transcripts from the livers of whole body Dpp4-/- displayed enrichment for inflammasome, p53, and senescence programs compared to littermate controls. High-fat high-cholesterol (HFHC)-feeding decreased Dpp4 expression in F4/80+ cells, with only minor changes in immune signaling. Moreover, in a lean mouse model of severe non-alcoholic fatty liver disease (NAFLD), phosphatidylethanolamine N-methyltransferase (Pemt -/-) mice fed with HFHC diet, we observed a 4-fold increase in circulating DPP4, disassociating its release from obesity. Lastly, we evaluated DPP4 levels in patients with hepatitis C infection with dysglycemia (HOMA-IR > 2) who underwent direct antiviral treatment (with or without ribavirin). DPP4 protein levels decreased with viral clearance, and DPP4 activity levels were reduced at longer-term follow-up in ribavirin-treated patients, although metabolic factors did not improve. These data suggest elevations in DPP4 during HCV infection are not primarily regulated by metabolic disturbances.

Perturbation of placental protein glycosylation by endoplasmic reticulum stress promotes maladaptation of maternal hepatic glucose metabolism

Placental hormones orchestrate maternal metabolic adaptations to support pregnancy. We hypothesized that placental ER stress, which characterizes early-onset pre-eclampsia (ePE), compromises glycosylation, reducing hormone bioactivity and these maladaptations predispose the mother to metabolic disease in later life. We demonstrate ER stress reduces the complexity and sialylation of trophoblast protein N-glycosylation, while aberrant glycosylation of vascular endothelial growth factor reduced its bioactivity. ER stress alters the expression of 66 of the 146 genes annotated with "protein glycosylation" and reduces the expression of sialyltransferases. Using mouse placental explants, we show ER stress promotes the secretion of mis-glycosylated glycoproteins. Pregnant mice carrying placentas with junctional zone-specific ER stress have reduced blood glucose, anomalous hepatic glucose metabolism, increased cellular stress and elevated DNA methyltransferase 3A. Using pregnancy-specific glycoproteins as a readout, we also demonstrate aberrant glycosylation of placental proteins in women with ePE, thus providing a mechanistic link between ePE and subsequent maternal metabolic disorders.

Serum clinical laboratory tests and risk of incident dementia: a prospective cohort study of 407,190 individuals

Prevention of dementia is a public health priority, and the identification of potential biomarkers may provide benefits for early detection and prevention. This study investigates the association of common serum laboratory tests with the risk of incident dementia. Among 407,190 participants from the UK Biobank (median follow-up of 9.19 years), we investigated the linear and nonlinear effects of 30 laboratory measures on the risk of all-cause dementia using Cox models and restricted cubic spline models. We found that dementia incidence was associated with low vitamin D concentration (hazard ratio 0.994, 95% confidence interval 0.993–0.996), indicators of endocrine disorders: IGF-1 level (P for non-linearity = 1.1E-05), testosterone level (P for non-linearity = 0.006); high sex-hormone-binding globulin level (HR 1.004, 95% CI: 1.003–1.006); reduced liver function: lower alanine aminotransferase (HR 0.990, 95% CI: 0.986–0.995); renal dysfunction: cystatin C level (P for non-linearity = 0.028); oxidative stress: lower urate level (HR 0.998, 95% CI: 0.998–0.999); lipids dysregulation: lower LDL (HR 0.918, 95% CI: 0.872–0.965) and triglycerides (HR 0.924, 95% CI: 0.882–0.967) concentrations; insulin resistance: high glucose (HR 1.093, 95% CI: 1.045–1.143) and HbA1c (HR 1.017, 95% CI: 1.009–1.025) levels; immune dysbiosis: C−reactive protein (P for non-linearity = 5.5E-09). In conclusion, markers of vitamin D deficiency, GH-IGF-1 axis disorders, bioactive sex hormone deficiency, reduced liver function, renal abnormalities, oxidation, insulin resistance, immune dysbiosis, and lipids dysregulation were associated with incident dementia. Our results support a contributory role of systemic disorders and diverse biological processes to onset of dementia.

Corin Missense Variants, Blood Pressure, and Hypertension in 11322 Black Individuals: Insights From REGARDS and the Jackson Heart Study.

BackgroundCorin enzyme contributes to the processing of inactive natriuretic peptides to bioactive hormones. In Black individuals, Corin gene variants (rs111253292 [Q568P] and rs75770792 [T555I]) have been previously reported to have a modest association with blood pressure (BP) and hypertension.Methods and ResultsWe evaluated the association of Corin genotype with BP traits, prevalent hypertension, and incident hypertension among self‐identified 11 322 Black Americans in the REGARDS (Reasons for Geographic and Racial Differences in Stroke) study and the JHS (Jackson Heart Study) using multivariable‐adjusted regression modeling. Multivariable‐adjusted genotype‐stratified differences in NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) and BNP (B‐type natriuretic peptide) levels were assessed. Genotype‐stratified NPPA and NPPB expression differences in healthy organ donor left atrial and left ventricular heart tissue (N=15) were also examined. The rs111253292 genotype was not associated with systolic BP (β±SE, 0.42±0.58; −1.24±0.82), diastolic BP (0.51±0.33; −0.41±0.46), mean arterial pressure (0.48±0.38; −0.68±0.51), and prevalent hypertension (odds ratio [OR], 0.93 [95% CI, 0.80–1.09]; OR, 0.79 [95% CI, 0.61–1.01]) in both REGARDS and JHS, respectively. The rs75770792 genotype was not associated with systolic BP (0.48±0.58; −1.26±0.81), diastolic BP (0.52±0.33; −0.33±0.45), mean arterial pressure (0.50±0.38; −0.63±0.50), and prevalent hypertension (OR, 1.02 [95% CI, 0.84–1.23]; OR, 0.87 [95% CI, 0.67–1.13]) in both cohorts, respectively. The Corin genotype was also not associated with incident hypertension (OR, 1.35 [95% CI, 0.94–1.93]; OR, 0.95 [95% CI, 0.64–1.39]) in the study cohorts. The NT‐proBNP levels in REGARDS and BNP levels in JHS were similar between the Corin genotype groups. In heart tissue, the NPPA and NPPB expression was similar between the genotype groups.Conclusions Corin gene variants observed more commonly in Black individuals are not associated with differences in NP expression, circulating NP levels, and BP or hypertension as previously reported in candidate gene studies. Understanding the genetic determinants of complex cardiovascular traits in underrepresented populations requires further evaluation.

METABOLICALLY HEALTHY OBESITY AND RISK FACTORS. THE ROLE OF ADIPOSE TISSUE

Objective: Metabolically healthy obesity (MHO) is a benign condition commonly associated with lower cardiovascular (CV) risk. Adipose tissue might be implicated in this condition through bioactive hormones, so-called adipokines. The aim of this study was to compare cardioprotective (omentin-1, adiponectin) with non-cardioprotective (visfatin, resistin, chemerin) adipokines in MHO versus metabolically unhealthy obese (MUO) patients. Design and method: Overall, 200 obese patients were studied (100 MHO and 100 MUO). MHO were those with less than 3 of the following criteria: (1) waist circumference &gt; 102 cm in males or &gt; 88 cm in females, (2) triglycerides &gt; 150 mg/dl or treatment for this abnormality, (3) HDL &lt; 40 mg/dl in males or &lt; 50 mg/dl in females or treatment for this abnormality (4) systolic blood pressure &gt; 130mmHg or diastolic blood pressure &gt; 85mmHg or treatment for hypertension and (5) fasting glucose &gt; 100 mg/dl or treatment for type 2 diabetes mellitus. MUO were those with 3 or more of the above criteria. Adipokines levels were measured by the Elisa method. Results: Omentin-1 and adiponectin were increased in MHO compared to MUO, whereas visfatin, resistin and chemerin were decreased. Statistically significant differences were observed only for omentin-1, visfatin and resistin. Conclusions: In healthy obese patients, cardioprotective omentin-1 was higher while non-cardioprotective visfatin and resistin were lower. This highlights a potential prognostic role of adipose tissue in classifying obese patients at decreased CV risk.

Characterization of Thyroid Hormones Antivertigo Effects in a Rat Model of Excitotoxically-Induced Vestibulopathy.

Impaired vestibular function induces disabling symptoms such as postural imbalance, impaired locomotion, vestibulo-ocular reflex alteration, impaired cognitive functions such as spatial disorientation, and vegetative deficits. These symptoms show up in sudden attacks in patients with Ménière or neuritis and may lead to emergency hospitalizations. To date, however, there is no curative solution to these pathologies and the effectiveness of treatments used to reduce symptoms in the management of patients is discussed. Thus, elucidating the biological mechanisms correlated to the expression kinetics of the vestibular syndrome is useful for the development of potential therapeutic candidates with a view to relieving patients and limiting emergency hospitalizations. Recently, a robust antivertigo effect of thyroxine (T4) was demonstrated in a rodent model of impaired vestibular function induced by unilateral surgical section of the vestibular nerve. The aim of the present study was to assess thyroid hormones L-T4 and triiodothyronine (T3) as well as the bioactive thyroid hormone metabolite TRIAC on a rodent model of acute unilateral vestibulopathy more representative of clinical vestibular pathology. To this end, a partial and transient unilateral suppression of peripheral vestibular inputs was induced by an excitotoxic lesion caused by transtympanic injection of kainic acid (TTK) into the inner ear of adult rats. Vestibular syndrome and functional recovery were studied by semi-quantitative and quantitative assessments of relevant posturo-locomotor parameters. In contrast to the effect previously demonstrated in the complete and irreversible vestibular injury model, administration of thyroxine in the TTK rodent model did not display significant antivertigo effect. However, it is noteworthy that administration of thyroxine showed trends to prevent posturo-locomotor alterations. Furthermore, the results of the current study suggested that a single dose of thyroxine is sufficient to induce the same effects on vestibular syndrome observed with sub-chronic administration, and that reducing the T4 dose may more efficiently prevent the appearance of vestibular deficits induced by the excitotoxic type lesion. Finally, comparison of the antivertigo effect of T4 in different vestibulopathy models enables us to determine the therapeutic indication in which thyroxine could be a potential therapeutic candidate.