Hormone Metabolism Research Articles

Altered gut microbiome and serum metabolome profiles associated with essential tremor.

The genetic predisposition and environmental factors both trigger the complex neurological dyskinesia of essential tremor (ET). Gut dysbiosis may facilitate the occurrence and development of neurological diseases. Therefore, it is worth exploring the inner connections between gut microbiota and ET.First, the gut microbiota of 19 ET patients and 21 healthy controls (HCs) were analysed with metagenomics approach. Second, the potential linkages between gut microbiome and serum metabolome profiles were explored by integrative analysis.The gut microbiota disorders were present in ET patients. The LEfSe method showed a significant decrease in Bacteroides. The functional analysis revealed that there were differences in gut microbial apoptosis, retinol metabolism, and steroid hormone biosynthesis pathways. The levels of various lipids and lipid-like molecules alter in serum of ET patients, which correlated with altered gut microbial abundance, indicating the alterations in lipid metabolism involved in apoptosis pathway in ET.All of these data point to the gut dysbiosis in ET, and some changed gut microbial species were linked to abnormalities in blood lipid metabolism, which open up new avenues for investigation into the pathophysiology of ET.

Folicular dynamics, endocrine profiles and endometrial gene expression in fertile and subfertile cows.

Context Subfertility has a negative impact on the productivity of beef cow herds; thus, it is relevant to unravel the mechanisms. Aims To study follicular development, body composition, concentrations of progesterone and metabolic hormones and their gene expression in the endometrium during the oestrus cycle. Methods Fertile and subfertile Hereford cows were classified at 25 (n =84) and 60 (n =25) months old, as (1) fertile, pregnant at first insemination at 25months, that became pregnantmore than three of five times at 60months (n =5), or (2) subfertile, i.e. failed to became pregnant during three inseminations at 25months, that became pregnant at fewer than two of the five opportunities at 60months (n =6). Key results Fertile cows had greater concentrations of insuling-like growth factor 1 (IGF-1), leptin and adiponectin (P P P P P Conclusions Differences in progesterone and metabolic hormones in plasma and follicular fluid and their endometrial expression are associated with the success of pregnancy in beef cows. Implications Strategies to improve the follicle and endometrial microenvironments are needed to improve the productivity of beef herds.

The MADS-Box Transcription Factor CaRIN Positively Regulates Chlorophyll Degradation During Pepper (Capsicum annuum L.) Fruit Ripening by Repressing the Expression of CaLhcb-P4

Pepper (Capsicum spp.) is an important global vegetable and spice, with fruit color being a key determinant of its commercial quality. However, the regulatory mechanisms underlying pepper fruit color are still not fully understood. This study focuses on the MADS-RIPENING INHIBITOR (MADS-RIN), a MADS-box transcription factor that regulates various aspects of fruit ripening, including pigmentation. We identified CaRIN, a homolog of tomato’s SlRIN, whose expression is closely associated with fruit ripening in pepper. Silencing CaRIN through virus-induced gene silencing (VIGS) resulted in increased chlorophyll and chlorophyll a content, reduced carotenoid accumulation, and uneven fruit coloration. Integrative analysis of the RNA-seq and DAP-seq data identified 77 target genes regulated by CaRIN, which was involved in processes such as chlorophyll metabolism and plant hormone signaling. Yeast one-hybrid (Y1H) and dual-luciferase (LUC) assays demonstrated that CaRIN directly bound to the promoter of CaLhcb-P4, repressing its expression. Downregulation of CaLhcb-P4 in pepper fruits via VIGS accelerated chlorophyll degradation. Additionally, CaRIN indirectly regulated multiple genes associated with chlorophyll and carotenoid metabolism, sugar transport, and cell wall degradation. These findings provide novel insights into the regulatory mechanisms of chlorophyll degradation during pepper fruit ripening, offering a foundation for further research and potential genetic improvement strategies.

Aggregated proinsulin in pancreatic β-cells is degraded by the autophagy pathway.

Insulin, a critical metabolic hormone to maintain blood glucose homeostasis, is synthesized and folded in the endoplasmic reticulum (ER) of pancreatic β-cells as the insulin precursor proinsulin. Proinsulin misfolding and aggregation detected in diabetic β-cells induces ER stress and obstructs normal trafficking, processing, and secretion of insulin, which eventually can result in pancreatic β-cell dedifferentiation and death. We have developed quantitative methods to measure misfolded and aggregated proinsulin in β-cells by utilizing proinsulin oligomer specific ELISA and Proximity Ligation Assay (PLA) assays. Under conditions of induced ER stress, both assays detected significant accumulation of aggregated proinsulin in β-cells. Proinsulin aggregation was also observed in isolated pancreatic islets cultured at high glucose levels. Moreover, high glucose in β-cells downregulated expression of genes mediating clearance of misfolded proteins from the secretory pathway through ER autophagy and ER-associated degradation (ERAD). Inhibition of autophagy in β-cells induced strong induction of misfolded proinsulin accumulation, whereas ERAD inhibition was not effective in generating proinsulin aggregates. Finally, we observed subcellular colocalization of aggregated proinsulin with protein markers of autophagosomes. Our results indicate that autophagy controls degradation of aggregated misfolded proinsulin under conditions of hyperglycemia and diabetes.

Modulation of Intestinal Flora: a Novel Immunotherapeutic Approach for Enhancing Thyroid Cancer Treatment.

Over the past 3years, there has been a growing interest in clinical research regarding the potential involvement of intestinal flora in thyroid cancer (TC). This review delves into the intricate connection between intestinal flora and TC, focusing on the particular intestinal flora that is directly linked to the disease and identifying which may be able to predict potential microbial markers of TC. In order to shed light on the inflammatory pathways connected to the onset of TC, we investigated the impact of intestinal flora on immune modulation and the connection between chronic inflammation when investigating the role of intestinal flora in the pathogenesis of TC. Furthermore, the potential role of intestinal flora metabolites in the regulation of thyroid function was clarified by exploring the effects of short-chain fatty acids and lipopolysaccharide on thyroid hormone synthesis and metabolism. Based on these findings, we further explore the effects of probiotics, prebiotics, postbiotics, vitamins, and trace elements.

Characteristics of polymorphism of genes involved in the regulation of glucose metabolism and steroid hormone synthesis in patients with polycystic ovary syndrome

Background: Polycystic ovary syndrome is an urgent problem of gynecological endocrinology. Currently, a number of genes have been studied that control glucose metabolism and are involved in the synthesis, conversion into an active form and transport of steroid hormones, mutations in which with a certain degree of reliability can serve as a diagnostic criterion for polycystic ovary syndrome. Aim: The aim of this study was to evaluate the PPARG Pro12Ala, INS 223HphI AT, and SHBG (TAAAA)n gene polymorphisms in patients with polycystic ovary syndrome and in healthy individuals. Materials and methods: The polymerase chain reaction method and restriction fragment length polymorphism analysis were used. The frequencies of alleles and genotypes of polymorphic variants were studied in 136 women with polycystic ovary syndrome and 47 women in the control group: Pro12Ala (PPARG gene), 223HphI AT, (INS gene) and (TAAAA)n repeats (SHBG gene). Results: The distribution of the allele and genotype frequencies for the PPARG (rs1801282) and INS (rs689) genes in patients with polycystic ovary syndrome and in healthy individuals did not differ. The distribution of the genotype frequencies in the group of women with polycystic ovary syndrome differed (p = 0.02) from that in the control group for the (TAAAA)n polymorphism in the SHBG gene. In the presence of a long repeat in the SHBG gene in at least one of the homologous chromosomes, the probability of a woman having polycystic ovary syndrome increases by 2.5 times. Patients with a verified A/A genotype (INS), in the presence of an SHBG gene allele with a long repeat, have a ten-fold higher risk of developing polycystic ovary syndrome than women with SHBG gene short alleles. Conclusions: Patients with long repeats in the SHBG gene are at risk for developing polycystic ovary syndrome with phenotypes A, B, and C, especially in combination with the presence of the A/A genotype, class I (INS).

The synergistic effects of citicoline and silymarin on liver injury and thyroid hormone disturbances in γ-irradiated rats.

Exposure to ionizing radiation is inevitable due to its extensive use in industrial and medical applications. The search for effective and safe natural therapeutic agents as alternatives to chemical drugs is crucial to mitigate their side effects. This study aimed to evaluate the effects of citicoline as a standalone treatment or in combination with the anti-hepatotoxic drug silymarin in protecting against liver injury caused by γ-radiation in rats. The rats were exposed to γ-radiation (7Gy) and treated with citicoline (300mg/kg/day) and/or silymarin (50mg/kg/day). The results showed that citicoline alleviated liver damage in irradiated rats by reducing hepatic malondialdehyde levels, serum aspartate aminotransferase activity, and inflammatory mediators such as tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and nuclear factor-kappa B (NF-κB). It also increased acetylcholine (ACh) levels and the gene expression of the anti-inflammatory protein α7 nicotinic acetylcholine receptor (α7nAChR). Additionally, citicoline improved serum triiodothyronine (T3) levels, thyroid hormone receptor beta (TRβ) gene expression, and iodothyronine deiodinase type 1 activity in hepatic tissues of irradiated rats. Furthermore, citicoline enhanced the effects of silymarin on thyroxine (T4), TRβ, ACh, and α7nAChR when co-administered in irradiated rats. Histopathological analysis confirmed these findings, demonstrating improved liver tissue structure. Citicoline mitigates γ-radiation-induced liver damage by reducing oxidative stress, activating the cholinergic anti-inflammatory pathway, and modulating thyroid hormone metabolism. These findings support the use of citicoline as a safe standalone treatment or as an adjuvant with silymarin for managing liver damage and thyroid hormone disturbances caused by γ-irradiation.

Effect of light fasting diet therapy on lipid metabolism and sex hormone levels in patients with polycystic ovary syndrome combined with infertility

Objective To investigate the effects of light fasting diet therapy, including flaxseed powder supplementation, on lipid metabolism and sex hormone levels in patients with polycystic ovary syndrome (PCOS) combined with infertility. Methods A total of 104 PCOS patients with combined infertility were divided into the control group (n = 52) and intervention group (n = 52) using a random number table method. Over a two-month study period, the control group received light fasting diet therapy with rice flour as a placebo, while the intervention group received light fasting diet therapy supplemented with flaxseed powder. Differences in general clinical data, anthropometric indicators, follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), progesterone (P), fasting plasma glucose (FPG), fasting insulin (FINS), Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C)) were compared between the two groups. Results After treatment, both groups showed significant reductions in FSH, LH, E2, and P levels compared to baseline (p < .05). In the intervention group, the mean FINS and HOMA-IR levels were significantly lower than those in the control group following 2 months of treatment (p < .05). Furthermore, TC, TG, and LDL-C levels were significantly reduced in the intervention group compared to the control group (p < .05). Conclusion Light fasting diet therapy, especially with flaxseed powder, improves obesity, lipid, and glucose metabolism disorders in PCOS patients with infertility. However, longitudinal studies are needed to better understand these associations and assess long-term effects before considering this intervention as a standard clinical recommendation for PCOS.

Dissection of the genetic basis and molecular mechanism of ovule number per ovary in oilseed rape (Brassica napus L.)

Ovule number per ovary (ONPO) determines the maximum potential of seed number per fruit that is a direct component of seed yield in crops. This study aimed to dissect the genetic basis and molecular mechanism of ONPO using a newly developed doubled haploid (DH) population in oilseed rape. In all the four investigated environments, the ONPO of 201 DH lines exhibited normal distribution with a wide variation from 22.6 to 41.8, suggesting quantitative inheritance appropriate for mapping QTL. A skeleton genetic map of 2111 markers within 19 linkage groups was developed, with a total of 1715.71 cM in length and an average of 0.82 cM between markers. Linkage mapping identified ten QTLs that were distributed on eight chromosomes and explained 7.0-15.9% of the phenotypic variance. Among these, four were identical to the reported and two were repeatedly detected with relatively large effects, highlighting their potential for marker-assisted selection. Phytohormone quantification of ovaries (at the ovule initiation stage) from two pools of high and low ONPO lines showed significant differences in the levels of nine sub-types of phytohormones, suggesting their important roles in regulating ovule number. Transcriptomic analysis identified 7689 differentially expressed genes (DEGs) between the two pools, of which nearly half were enriched into functional categories of reported genes regulating ONPO, including protein, RNA, signalling, miscellaneous, development, hormone metabolism, and tetrapyrrole synthesis. Integration of linkage QTL mapping, transcriptome sequencing and BLAST analysis identified 15 homologues of reported ovule number genes and 327 DEGs in the QTL regions, which were considered as direct and potential candidate genes. These findings propose further insights into the genetic basis and molecular mechanisms of ONPO, which will facilitate future gene cloning and genetic improvement for enhancing seed yield in oilseed rape.

P-63 PREVENTION OF POSSIBLE ABORTIONS IN PREGNANT WOMEN WITH REFETOFF SYNDROME USING METFORMIN AND THUS ACHIEVING A HEALTHY BIRTH

Abstract Introduction Refetoff syndrome (RS) is an autosomal dominantly inherited rare disease (1/40,000), characterized by thyroid hormone resistance (THR) mostly caused by Thyroid Hormone Receptor Beta (THR-B) gene defect. In the pregnancy period of female RS patients, the probability of live birth may decrease to 15%. It has been reported in the literature that metformin has effects on the thyroid hormone metabolism. Two female patients with RS being followed up in our center had pregnancy period that resulted in healthy deliveries with the use of metformin. This observation led us to question that metformin treatment may have positive effects in pregnancy of these patients by unknown mechanism of THR. We could not find any case reports or studies in the literature about the pregnancy periods in patients with RS, so we wanted to share our follow-up experience. Clinical Case Patient A and B were siblings with genetically proven THR-B mutation (figure 1). Patient A was on metformin treatment for insulin resistance before pregnancy. Her previous two pregnancies resulted in miscarriage following metformin discontinuation in pregnancy. In her third pregnancy under our follow-up, metformin treatment was continued. She completed the pregnancy without any problem and gave birth to healthy twins. Patient B, sister of Patient A, had two pregnancies. She used metformin in both pregnancies because of the favorable outcome in her sister. There were no problems in her pregnancies. The use of metformin has been shown to decrease TSH levels in patients with prediabetes and diabetes. The studies emphasize that metformin leads to a decrease in TSH values in individuals with subclinical or overt hypothyroidism, but this effect is not seen in healthy euthyroid patients. There are also reports that the effect of metformin leads to a decrease in thyroid hormone levels as well as thyroid gland and nodule size. In the literature search, we could only find a case report about metformin use in RS. In the report, metformin was started in a 28-year-old male RS patient due to a diabetic picture that developed over time. THR improved after metformin, but after a while metformin was discontinued due to dyspeptic complaints. Following the cessation of metformin THR became severe again. Although the exact mechanism of the thyroid suppressive effects of metformin is not clearly known, it is hypothesized that metformin, a compound that can cross the blood-brain barrier, increases the number and affinity of thyroid hormone receptors in the pituitary and hypothalamus, causes an increase in central dopaminergic activity, and as a result increases the pituitary feedback effect of peripheral thyroid hormones. Conclusion The incidence of healthy births in patients with RS is low. When we combine the limited literature data with our experience, we suggest that metformin treatment may contribute positively to a healthier pregnancy outcome in patients with RS.Figure 1:The pedigree of the family with Refetoff syndrome Table 1:Summary of pregnancies Table 2:Blood and genetic results of patients and* The records of two patients with Refetoff syndrome who were followed up in our center were obtained from the electronic health records.

Abscission zone metabolism impacts pre- and post-harvest fruit quality: a very attaching story

The function of abscission zones (AZs) determines the timing of fleshy fruit abscission, with important consequences not only for the optimal fruit harvest, but also on the overall final fruit quality. In this context, chemical treatments are commonly used at different stages of fruit development to control fruit abscission, which can also have positive or negative effects on fruit quality. In the current review, we examine commonly used chemicals that affect the metabolic activity in the AZs of fleshy fruit, in addition to their effects on fruit quality characteristics. The main hormone metabolism and signaling in the AZ include that of ethylene, auxin, abscisic acid and jasmonates, and the molecular components that are involved are covered and discussed, in addition to how these hormones work together to regulate AZ activity and hence, affect fruit quality. We focus on studies that have provided new insight into possible protein complexes that function in the AZ, including multiple MADS-box transcription factors, with potential overlapping regulatory roles which exist between AZ development, ethylene production, AZ activation, fruit ripening and overall fruit quality. The view of the AZ as a cross roads where multiple pathways and signals are integrated is discussed.

Investigating the role and mechanisms of bisphenol compounds in premature ovarian insufficiency using computational biology and bioinformatics.

Premature Ovarian Insufficiency refers to the premature decline in ovarian function before the age of 40, resulting in menstrual irregularities or complete cessation of menstruation, and affecting fertility. Widely used bisphenol compounds may have potential health effects, including premature ovarian insufficiency (POI). This study employs computational biology and bioinformatics to investigate the effects of bisphenols (BPs) on POI. Using bioinformatics tools, we identified potential target genes related to both bisphenols and POI, and conducted functional enrichment analysis. Further, we calculated differentially expressed genes for POI, extracted core networks, and explored immune function and screened core genes. Molecular docking and molecular dynamics simulations were used to explore the stable binding between bisphenols and core POI genes. Our results constructed a protein network of 56 potential target genes and extracted core subnetworks. Functional enrichment analysis indicated that estrogen metabolism, estrogen receptor pathways, steroid hormone metabolism, and carbohydrate and lipid metabolism may be involved in the process of BPs-induced POI. The differentially expressed genes obtained through further screening, CYP1A1 and CYP19A1, were subjected to molecular docking and dynamics simulations to reveal the mechanism by which bisphenols participate in estrogen metabolism through their stable binding. Our findings underscore the role of bisphenols in inducing POI and the potential mechanisms involved, providing new directions for further epidemiological and molecular biological research into this regulatory process.

Bisphenol F (BPF) exposure impairs sperm quality and offspring development in male zebrafish.

Bisphenol F (BPF), a substitute for bisphenol A (BPA), is widely used in consumer products, increasing the potential for environmental exposure. Our study investigated the reproductive effects of BPF on adult male zebrafish and explored its toxicological mechanisms, as well as its intergenerational effects. Adult male zebrafish were exposed to BPF concentrations of 0, 50, 500, 2500, and 5000 nM for 21 days. We evaluated sperm cell quantity and quality, hormonal markers testosterone (T) and vitellogenin (VTG), gene expression profiles related to hormone synthesis, metabolism, apoptosis, cell cycle, sexual behavior, and offspring health metrics including survival, development and locomotion. BPF exposure did not significantly affect body weight or gonadal index. However, at 500 and 2500 nM, a significant reduction in sperm count was observed. BPF exposure led to decreased serum T and increased hepatic VTG levels, indicating hormonal disruption. At 50 nM, BPF initiated sperm apoptosis, and at higher doses, it disrupted sperm meiosis, affecting cell distribution. This exposure negatively impacted sperm quality, reduced offspring survival rates, and altered sperm motility in adult fish. Offspring from BPF-exposed groups showed developmental issues, including increased mortality, delayed developmental stages, abnormal tail coiling and heart rate, which correlated with paternal sperm count and quality changes, alterations in T and VTG levels, and cell cycle phase distributions. Our study demonstrated that BPF exposure significantly impacted sperm quality, characterized by reduced sperm count and altered motility patterns, leading to developmental anomalies in offspring. These novel findings highlight the need for further research into BPF's reproductive and developmental toxicity, emphasizing the potential risks to aquatic ecosystems and human health. The observed effects on sperm quality, hormonal balance, and offspring development provide new insights into the reproductive toxicity profile of BPF.

24-epibrassinolide regulates oxytetracycline-induced phytotoxicity and its detoxification mechanism.

Oxytetracycline (OTC), a crop-absorbable antibiotic, poses a health risk to humans through the food chain. Conversely, 24-epibrassinolide (EBL), a plant growth hormone, mitigates the toxic effects of various pollutants on plants. However, the mechanism by which exogenous EBL affects the growth of rape seedlings exposed to OTC remains largely unknown. In this study, we found that environmental OTC concentrations significantly inhibited plant growth and metabolism, whereas exogenous EBL could restore plant growth characteristics. Exogenous EBL significantly decreased reactive oxygen species (ROS) accumulation, alleviating OTC-induced cell membrane lipid peroxidation. This was achieved by increasing the antioxidant capacity and secondary metabolism levels. Notably, our findings suggested that EBL stimulated glutathione S-transferase (GST) and glutathione reductase (GR) activities, enhancing reduced glutathione synthesis and participating in plant OTC detoxification. OTC residues in EBL + OTC-treated seedlings at 21 d were significantly reduced by 29 % compared with OTC alone. Further transcriptomic and metabolomic analyses revealed that the differentially expressed genes and metabolites in the EBL and OTC alone or combined treatment groups were primarily involved in the regulation of phenylpropanoid biosynthesis, glutathione metabolism, and lant hormone signal transduction pathways in response to phytotoxic effects and detoxification mechanisms, as compared to the control group.

Metabolomic Changes in Major Depressive Disorder Adolescent Females with or without Suicide Attempts.

The incidence of Major Depressive Disorder (MDD) is high among adolescent females, and MDD is often accompanied by suicide attempts (SAs), which have a serious negative impact on health. However, changes in lipids, thyroid hormone, and brain metabolism among female adolescents with MDD and the relationships between these three markers and MDD with SA have yet to be elucidated. This study enrolled 71 MDD patients with SA (MDD+SA), 66 MDD patients without SA (MDD-SA), and 47 healthy controls (HCs). We analysed the lipid and thyroid hormone levels and magnetic resonance spectroscopy results of the subjects. Low levels of social support, high levels of life stress, and high levels of suicidal ideation (SI) were risk factors for SA. In MDD patients, 1) thyroid stimulating hormone was positively correlated with triglyceride (TG) and N-acetyl aspartic acid (NAA)/creatinine in the prefrontal cortex (PFC) and negatively correlated with high-density lipoprotein and the choline/creatinine in the thalamus; 2) free thyroxine was negatively correlated with the choline/creatinine in the thalamus; 3) total cholesterol, TG, low-density lipoprotein, and choline/NAA in the PFC were positively correlated with the severity of SI and suicide risk; and 4) NAA/creatinine in the thalamus was negatively correlated with the severity of SI and suicide risk. In female adolescents with MDD, there are significant synergistic changes in lipids, thyroid hormones, and brain metabolism-related factors, and the changes in these indicators may be related to the pathological mechanism of SA.

The Hubungan Lama Pemakaian Suntik DMPA dengan Penurunan Libido pada Akseptor Suntik DMPA di Praktik Mandiri Bidan Hana Sri Wuryaningsih Parakan

Long-term use of DMPA injectable contraceptives can lower estrogen levels, affect hormone metabolism, and lower serum estradiol levels, resulting in decreased female sexual function. Injectable DMPA birth control shows significant sexual dysfunction effects if used for more than 2 years. The purpose of this study was to determine the relationship between prolonged use and decreased libido in DMPA injectable birth control acceptors at PMB Hana Sri Wuryaningsih. The research design uses descriptive correlative with a cross sectional approach. The population in this study was all DMPA injectable KB acceptors at PMB Hana Sri Wuryaningsih as many as 141 people. The sampling technique uses Purposive sampling. The number of samples was 104 respondents. This research instrument used questionnaires. Univariate analysis with frequency distribution table and bivariate analysis with Chi Square test.

The relationship between metabolic hormone levels and the prevalence of hypertension in people under 45 years of age

Among the various factors potentially involved in the pathogenesis of cardiovascular diseases, arterial hypertension (HTN), in the structure of which the proportion of young people increases, is still the most common risk factor for the development of serious cardiovascular complications. The development of structural and functional disorders associated with HTN is accompanied by an increase or decrease in markers of metabolic disorders. Objective. Тo study the prevalence of HTN in young people of working age and childbearing age, depending on the levels of metabolic hormones. Design and methods. The study included 1,340 people from the Novosibirsk population sample aged 25–44 years. HTN was diagnosed in case of the average systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg. The levels of amylin, C-peptide, ghrelin, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide 1 (GLP-1), glucagon, insulin, pancreatic polypeptide (PP), and peptide YY (PYY) were determined by multiplex analysis. Results. In the quartile with the highest values of amylin, C-peptide, GIP, GLP-1 and PP, the prevalence of HTN is significantly higher compared to Q1. In the group of HTN patients, the levels of amylin, C-peptide, ghrelin, GIP, GLP-1, insulin and PP were 2,4 (p &lt; 0,0001), 1,4 (p &lt; 0,0001), 1,3 (p = 0,001), 1,3 (p = 0,003), 1,6 (p = 0,001), 1,2 (p = 0,002) and 1,4 (p = 0,006) times higher, respectively, in comparison with persons without HTN. Conclusions. The prevalence of HTN is associated with high values of amylin, ghrelin, glucagon, insulin and C-peptide. The chance of HTN increases starting from the second quartile of amylin and increases with each quartile.

Impact of dapagliflozin on metabolic phenotype, hormone levels, and fertility in female mice after prolonged high-fat diet.

A long-term high-fat diet (HFD) cause obesity and infertility through hypothalamic inflammation and insulin resistance, leading to metabolic abnormalities and ovulation dysfunction. The sodium-glucose cotransporter 2 inhibitors (SGLT2i) have emerged as a treatment for type 2 diabetic patients, regulating adipose tissue metabolism, hypothalamic inflammation, and ovulation in women with polycystic ovary syndrome (PCOS). The study aimed to investigate the pharmacological effects of dapagliflozin on improving insulin resistance, energy metabolism, sex hormones, and fertility in female mice following prolonged consumption of HFD. At 6 weeks of age, female mice were fed a HFD and treated with dapagliflozin. Serum hormone concentrations and inflammatory factors in mice aged 28 weeks or 38 weeks were quantified using ultrasensitive enzyme-linked immunosorbent assays (ELISAs). Metabolic parameters were also assessed and documented at different stages of the experiment. At 34 weeks of age, half of the experimental mice in each of the four groups fed with standard chow were mated with male mice. Pregnancy rate, abortion rate, pregnancy-related deaths, and perinatal outcomes were systematically recorded. After 16 weeks of HFD feeding, dapagliflozin significantly attenuated visceral fat deposition, weight gain, glucose intolerance, and insulin resistance induced by the diet. However, these effects diminished after 32 weeks. Unexpectedly, neither HFD nor dapagliflozin treatment elicited any significant changes in serum IL-6 and TNFα levels. Throughout the experiment period, dapagliflozin exhibited favorable effects on reproductive function along with insulin sensitivity and luteinizing hormone (LH) release from the pituitary gland. In conclusion, this study demonstrates that dapagliflozin alleviated HFD-induced reproductive dysfunction independently of obesity, peripheral tissue insulin resistance, and systemic inflammation, suggesting its potential as a promising treatment for diet-related ovulation disorders.

Deciphering the Transcriptional Metabolic Profile of Adipose-Derived Stem Cells During Osteogenic Differentiation and Epigenetic Drug Treatment.

Adipose-derived mesenchymal stem cells (ASCs) are commonly employed in clinical treatment for various diseases due to their ability to differentiate into multi-lineage and anti-inflammatory/immunomodulatory properties. Preclinical studies support their use for bone regeneration, healing, and the improvement of functional outcomes. However, a deeper understanding of the molecular mechanisms underlying ASC biology is crucial to identifying key regulatory pathways that influence differentiation and enhance regenerative potential. In this study, we employed the NanoString nCounter technology, an advanced multiplexed digital counting method of RNA molecules, to comprehensively characterize differentially expressed transcripts involved in metabolic pathways at distinct time points in osteogenically differentiating ASCs treated with or without the pan-DNMT inhibitor RG108. In silico annotation and gene ontology analysis highlighted the activation of ethanol oxidation, ROS regulation, retinoic acid metabolism, and steroid hormone metabolism, as well as in the metabolism of lipids, amino acids, and nucleotides, and pinpointed potential new osteogenic drivers like AOX1 and ADH1A. RG108-treated cells, in addition to the upregulation of the osteogenesis-related markers RUNX2 and ALPL, showed statistically significant alterations in genes implicated in transcriptional control (MYCN, MYB, TP63, and IRF1), ethanol oxidation (ADH1C, ADH4, ADH6, and ADH7), and glucose metabolism (SLC2A3). These findings highlight the complex interplay of the metabolic, structural, and signaling pathways that orchestrate osteogenic differentiation. Furthermore, this study underscores the potential of epigenetic drugs like RG108 to enhance ASC properties, paving the way for more effective and personalized cell-based therapies for bone regeneration.

Stress and Strain: Differentiating the Responses to High and Moderate Heat Loads and Subsequent Recovery in Grain-Fed Feedlot Steers-Metabolic Hormones.

The extent of endocrine changes in response to various levels of heat stress and subsequent recovery is not well understood. Two cohorts of 12 Black Angus steers were housed in climate-controlled rooms (CCR) and subjected to three thermal periods: PreChallenge (5 d), Challenge (7 d) and Recovery (5 d). PreChallenge and Recovery provided thermoneutral conditions. The Challenge simulated a strong heatwave. Finally, the steers were maintained in outdoor pens for 38 d. Rumen temperature (RumT), respiration rate (RR) and panting score (PS) were intensively measured in the CCR. Dry matter intake (DMI) was determined daily. The steers were bled most days, and a rectal temperature (RecT) was taken also. Plasma concentrations of TSH, prolactin, T3, T4, insulin, leptin and adiponectin were determined. During the Challenge, RumT, RecT, RR and PS rose; DMI was reduced. Plasma T3, T4 and adiponectin levels fell also. In Recovery, RumT, RecT, RR and PS fell below the PreChallenge mean. DMI partially recovered. T4 and adiponectin levels remained suppressed alongside lowered insulin. There were linear relationships between T3 concentration and THI, and T3 and T4 levels and DMI only. We highlight comparisons with previously reported metabolic hormone responses of grain-fed Black Angus steers to a moderate-heat-load challenge.