Endokrynologia Polska最新文献

Introduction: MicroRNAs (miRNAs) are involved in the pathogenesis of various diseases. Although the role of miR-490-5p in bone-related disorders has been reported, its regulatory mechanism in osteoporotic fractures remains unclear. Therefore, this study aims to investigate the functional mechanism of miR-490-5p in osteoporotic fractures.

Material and methods: Human osteoblast cells (hFOB1.19) were induced to undergo differentiation, during which the expression levels of miR-490-5p, forkhead box P3 (FOXP3), and claudin 14 (CLDN14) were quantified using real-time quantitative polymerase chain reaction (RT-qPCR). Osteoporotic animal models and osteoporotic fracture models were established to evaluate miR-490-5p expression. Osteoporosis-related biomarkers were assessed via alkaline phosphatase (ALP) activity assays and commercial assay kits. Rescue experiments were performed to validate the findings.

Results: miR-490-5p inhibited osteoblast differentiation. It was highly expressed in osteoporotic bone tissue and at the fracture ends of osteoporotic fractures. Mechanistically, miR-490-5p inhibited the expression of FOXP3 by binding to the 3'UTR of FOXP3, thereby suppressing RUNX1 transcriptional activation of CLDN14, leading to the progression of osteoporotic fractures.

Conclusion: miR-490-5p inhibits RUNX1 transcriptional activation of CLDN14 through FOXP3, promoting the development of osteoporotic fractures.

Introduction: Thiamine-responsive megaloblastic anaemia syndrome (TRMA) is a rare genetic disease caused by mutations in the SLC19A2 gene that encodes thiamine transporter 1 (THTR-1). The common manifestations are diabetes, anaemia, and deafness. The pathogenic mechanism has not yet been clarified.

Material and methods: Rat pancreatic islet tumour cells INS.1 were used to construct cell lines stably overexpressing wild-type SLC19A2 and SLC19A2 (c.1409insT) mutants. The mRNA and protein expressions of THTR-1 and endoplasmic reticulum stress (ERS)-associated factors were detected by real-time fluorescence quantitative polymerase chain reaction (PCR) and western blot methods, respectively. Flow cytometry and cell counting kit-8 were used to analyse the effects of SLC19A2 (c.1409insT) mutation on cell apoptosis and proliferation, respectively. 4-Phenylbutyric acid (4-PBA), an ERS inhibitor, was administered to SLC19A2 (c.1409insT)-mutated INS.1 cells, and then the mRNA and protein expressions of ERS-related factors in cells were detected.

Results: Mutations in the SLC19A2 (c.1409insT) promote apoptosis and inhibit cell proliferation, thereby upregulating the mRNA and protein levels of ERS-associated factors glucose-regulated protein 78, protein kinase R-like endoplasmic reticulum kinase, C/EBP homologous protein, and activating transcription factor 4. 4-PBA could inhibit ERS caused by SLC19A2 (c.1409insT) mutations, downregulate mRNA and protein expression levels of GRP78, CHOP, and phosphorylated eukaryotic initiation factor 2α, and protect pancreatic islet β-cells.

Conclusion: THTR-1 deficiency triggers diabetes in TRMA patients through ERS, and 4-PBA protects pancreatic islet β-cells by inhibiting ERS, which provides new ideas and intervention targets for the prevention and treatment of TRMA and diabetes.

Introduction: Obesity, type 1 diabetes mellitus (T1DM), and type 2 diabetes mellitus (T2DM) are metabolic disorders and global problems, the most significant complication of which is endothelial damage and the accompanying platelet hyperactivity, which leads to cardiovascular disease. Signal peptide, CUB, and epidermal growth factor (EGF)-like domain-containing protein 1 (SCUBE1) is a protein secreted by both the endothelial cells and platelets. The present study compares the serum SCUBE1 levels of rats with experimentally induced obesity, T1DM, T2DM, and control subjects. It makes a comparative evaluation of the relationship between the groups.

Material and methods: Included in the study were 28 male Sprague-Dawley rats that were allocated to the obese group fed a high-fat diet (HFD); the T2DM group that received HFD plus a single dose of streptozocin (STZ); the T1DM group that received only STZ; and the control group. Serum SCUBE1 was analyzed using the enzyme-linked immunosorbent assay (ELISA) method, and caspase-3 (Cas-3), interleukin 6 (IL-6), interferon gamma (INF-γ), and superoxide dismutase (SOD) expressions in the liver and pancreas of rats were evaluated using immunohistochemical methods.

Results: Serum SCUBE1 levels were significantly higher in the obese, T1DM, and T2DM groups than in the control group, but there was no significant difference among the obese, T1DM, and T2DM groups. The study identified a significant relationship between serum SCUBE1 level and hepatic CAS3, IL-6, and SOD expressions and pancreatic SOD expression.

Conclusions: The expression of SCUBE1 in both endothelial cells and platelets suggests that SCUBE1 could be used as a marker of endothelial dysfunction and platelet hyperactivity, which are significant complications in obesity, T1DM, and T2DM.

Introduction: This study investigates the link between mild autonomous cortisol secretion (MACS) in adrenal incidentaloma (AI) patients and the occurrence and severity of cardiovascular and metabolic comorbidities. It aims to provide a detailed overview of this relationship, highlight gaps in current research, and propose directions for future studies.

Material and methods: We conducted a retrospective analysis at Ankara City Hospital's Endocrine Department outpatient clinic, reviewing 627 AI patients from February 2019 to May 2021. The study involved a detailed analysis of clinical records, hormonal evaluations, and imaging, focusing on differentiating MACS from non-functioning adrenal incidentalomas (NFAI) and examining the impact of MACS on associated health conditions.

Results: The study found that MACS patients had a statistically higher incidence of diabetes mellitus (35% vs. 20%), hypertension (60% vs. 45%), hyperlipidaemia (40% vs. 25%), and coronary artery disease (30% vs. 15%) compared to the NFAI group. Independent predictors of MACS included the presence of bilateral adrenal masses, larger adrenal mass diameter (with a cutoff value of ≥ 18.5 mm, showing 83% sensitivity and 56% specificity for predicting MACS, and lower dehydroepiandrosterone sulphate (DHEAS) levels (≤ 49.31 μg/dL predicting MACS, with 61% sensitivity and 73% specificity).

Conclusion: This research underscores the critical clinical implications of detecting MACS in AI patients, particularly its association with increased cardiovascular and metabolic risks. It calls for vigilant screening and a comprehensive management approach for affected patients. Additionally, the findings highlight the need for further studies to improve patient care and outcomes in this population.

Acromegaly is a rare, endocrine condition characterized by autonomous excessive secretion of growth hormone, causing numerous complications, including impairment of bone microarchitecture. The increased bone turnover observed in acromegaly can lead to bone fragility and elevated risk of vertebral fractures despite normal bone mineral density measured with dual-energy X-ray-absorptiometry. Treatment of acromegaly improves bone architecture; however, it does not completely reverse this process, and the increased vertebral fracture risk persists despite adequate disease control. Sclerostin, a product of the SOST gene, is one of the markers of bone turnover. Elevated sclerostin levels are correlated with impaired bone formation and serve as an independent risk factor for osteoporotic fractures in postmenopausal women. Inhibition of sclerostin is currently used in the treatment of osteoporosis in postmenopausal women. Considering the increased risk of vertebral fractures in patients with acromegaly, it is important to understand the potential role of sclerostin in this group of patients. This systematic review aimed to evaluate sclerostin levels in patients with acromegaly in comparison to the general population. The search strategy led to 7 studies meeting the inclusion criteria, which resulted in the inclusion of 385 patients with acromegaly in the final analysis. Available studies have provided conflicting results regarding sclerostin levels in acromegaly. Most of the studies showed lower sclerostin concentrations in patients with acromegaly compared to healthy controls, or no differences among groups. Only one study reported positive correlation between sclerostin levels and acromegaly, and its activity, expressed as insulin-like growth factor (IGF-1) and growth hormone (GH) concentrations. The rarity of acromegaly, small subject numbers, and heterogeneity of the groups could impact the results.

Cachexia is characterized by decreased body weight resulting from the predominance of catabolic over anabolic metabolism. The condition is likely to be caused by a decline in the body's physiological reserves, which leads to breakdown of homeostatic processes in patients weakened by diseases. The overlapping disease is the frailty syndrome, i.e., a group of symptoms (decreases in skeletal muscle mass (sarcopenia) and bone density) that occur in the aging process. Additionally, cachexia is associated with elevated levels of various pro-catabolic indicators. Importantly, this condition responds rather poorly to standard nutritional support or medical nutrition, and is often accompanied by loss of appetite, which makes therapy much more difficult. The result is worsening of the patient's somatic condition and an increased risk of premature death. Compounds representing the class of selective androgen receptor modulators (SARMs) are a relatively new group of substances that could be used in the future to improve the condition of patients with cachexia and frailty syndrome. Two compounds, GTx-024/MK-2866 (enobosarm) and GSK2881078, are currently being tested in clinical trials. This paper discusses their effects and potential use in future cachexia and frailty therapies.

As life expectancy increases worldwide, diseases associated with aging are becoming an increasing challenge in medical care. One of them is senile osteoporosis, which often leads to fragility fractures and numerous subsequent complications, such as disability, chronic pain, and even death. Although osteoporosis is common in the elderly, data on its epidemiology, pathogenesis, and treatment are still lacking. Moreover, it is often diagnosed and treated only after a fracture occurs, which is associated with a significant reduction in quality of life and the generation of high costs. A better understanding of the pathomechanisms of senile osteoporosis is essential for early diagnosis, prevention, and the development of new therapies. This article reviewed current medical knowledge on osteoporosis in the elderly and its epidemiology, etiopathogenesis, diagnosis, and treatment.

Precise assessment of Graves` orbitopathy (GO) predicts therapeutic strategies. Various imaging techniques and different measurement methods are used, but there is a lack of standardization. Traditionally, the Clinical Activity Score (CAS) has been used for assessing GO, especially for evaluating disease activity to predict response to glucocorticoid (GC) therapy, but technological developments have led to a shift towards more objective imaging methods that offer accuracy. Imaging methods for Graves' orbitopathy assessment include ultrasonography (USG), computed tomography (CT), magnetic resonance imaging (MRI), and single photon emission computed tomography (SPECT). These can be divided into those that assess disease activity (MRI, SPECT) and those that assess disease severity (USG, CT, MRI, SPECT). USG is the accessible first-aid tool that provides non-invasive imaging of orbital structures, with a short time of examination making it highly suitable for initial evaluation and monitoring of GO. It does have limitations, particularly in visualizing the apex of the orbit. Initially, orbital CT was thought to provide more accurate morphological information, particularly in extraocular muscles, and superior visualization of bone structures compared to MRI, making it the imaging modality of choice prior to planned orbital decompression; however, it has difficulty in accurately assessing the inflammatory activity stages of GO. Although CT offers a better view of deeper-lying tissue, it is limited by radiation exposure. MRI is best suited for follow-up examinations because it offers superior soft tissue visualization and precise tissue differentiation. However, it is not specific for orbital changes, the examination is very expensive, and it is rarely available. Recent literature proposes that nuclear medicine imaging techniques may be the best discipline for assessing GO. SPECT fused with low-dose CT scans is now used to increase the diagnostic value of the investigation. It provides functional information on top of the anatomical images. The use of cost-effective radioisotope - technetium-99m (99mTc)-DTPA - gives great diagnostic results with short examination time, low radiation exposure, and satisfactory spatial resolution. Nowadays, 36 years after CAS development and with technological improvement, researchers aim to integrate artificial intelligence tools with SPECT/CT imaging to diagnose and stage GO activity more effectively.