INTRODUCTION: The acid-labile subunit (ALS) is a protein best known for its function in stabilising the insulin like growth factor-1/2-insulin-like growth factor-1 binding protein 3/5 (IGF-1/2-IGFBP3/5) binary complex by...INTRODUCTION: The acid-labile subunit (ALS) is a protein best known for its function in stabilising the insulin like growth factor-1/2-insulin-like growth factor-1 binding protein 3/5 (IGF-1/2-IGFBP3/5) binary complex by creating the ternary complex and in consequence regulating the biological activity of IGF-1. The aim of the study was to assess ALS concentrations in a chosen population of children with short stature taking into account their clinical diagnosis. MATERIAL AND METHODS: A total of 109 prepubertal children were involved in the study - 85 children in the study group and 24 in controls. In all the children IGF-1, IGFBP3, and ALS were measured. The study group was divided according to diagnosis into groups: growth hormone deficiency (GHD), constitutional delay of growth and puberty (CDGP), idiopathic short stature (ISS), and familial short stature (FSS). RESULTS: In the control group the ALS concentration ranged from 4.81 to 13.66 μg/mL. In the whole study group the ALS concentration ranged from 2.73 to 15.81 μg/mL. The difference between both groups was statistically significant (p < 0.0001, R = 0.39). A strong, statistically significant correlation between ALS levels and age was observed, but only in the study group (p < 0.0001, r = 0.59). The ALS standard deviation score (SDS) was not significantly different between the control and CDGP children (p = 0.0644). The ALS concentration was significantly lower in children with short stature. There was, however, no difference between the subgroups of the study group. CONCLUSION: There was no significant difference in ALS SDS between the control group and children with constitutional delay of growth and development. The usefulness of ALS in routine short stature diagnostics is uncertain, but it might play a role in the diagnosis of children with ISS and CDGP in the future.
INTRODUCTION: The aim of the study was presentation of the data on falls in a cohort of postmenopausal women in a 10-year prospective longitudinal observation. MATERIAL AND METHODS: 640 postmenopausal women at baseline a...INTRODUCTION: The aim of the study was presentation of the data on falls in a cohort of postmenopausal women in a 10-year prospective longitudinal observation. MATERIAL AND METHODS: 640 postmenopausal women at baseline age above 55 years were included. The cohort was randomly selected from the population of the whole Racibórz district. Data on falls and fracture incidence were gathered yearly. RESULTS: 256 (40%) women had no falls, and in 384 (60%) subjects at least one fall was noted. The number of women with 1, 2, and 3 or more falls were 115, 62, and 207, respectively. The total number of falls was 1988. Mean baseline age in those who noted falls was 65.7 ± 7.02 years, and it was significantly higher than in the rest of the patients (64.1 ± 6.75; p<0.01). During follow-up 190 osteoporotic fractures were noted in 129 patients. Falls were proven to have a strong, significant relationship with fracture (chi-square test = 80.5; p < 0.0001). Among potential clinical factors only diabetes type 1 (chi-square test = 5.80; p < 0.05) and depression (chi-square test = 3.82; p < 0.05) influenced falls incidence. The risk of falls was increased in cases of greater numbers of clinical risk factors (chi-square test = 28.4 df = 5; p < 0.0001). CONCLUSIONS: In long-term follow-up in postmenopausal women, falls were frequently observed, and their occurrence increased the fracture rate. Diabetes type 1 and depression increase the fall rate, which suggests the necessity of implementation of some preventive procedures.
INTRODUCTION: The aim of the study was to present data on risk factors for fractures in various parts of the skeleton in a cohort of postmenopausal women during a 10-year prospective observation period. It can be hypothe...INTRODUCTION: The aim of the study was to present data on risk factors for fractures in various parts of the skeleton in a cohort of postmenopausal women during a 10-year prospective observation period. It can be hypothesised that fracture risk factors should be different for spine, hip, and peripheral fractures. MATERIAL AND METHODS: 640 postmenopausal women at mean baseline age was 65.0 ± 6.9 years were enrolled into the study. The cohort was randomly selected from the population of the entire Racibórz district. Data on the incidence of fractures and falls were updated annually during the 10-year follow-up period. Information on clinical risk factors for fractures was collected at baseline. RESULTS: During the observation period, 190 low-traumatic fractures were recorded in 129 patients. The following number of fractures was observed: hip 15, spine 30, non-hip fractures other than spine 145 (including 81 forearm fractures). The effect of falls was insignificant in the case of spine fractures (chi-square test: 3.64; p = 0.06). For all other skeletal sites, the incidence of fractures was significantly increased by falls, with the greatest effect observed for forearm fractures and non-spine and non-hip fractures (chi-square test for hip, forearm, and all non-spine, non-hip fractures was 6.43, p < 0.05; 42.7, p < 0.0001 and 66.7, p < 0.0001, respectively). To determine the factors having a significant impact on the incidence of fractures during the observation period, logistic regression was used separately in subgroups. The following risk factors were taken into account: age, height, body weight, bone mineral density (BMD) at the femoral neck as expressed by T-score, rheumatoid arthritis, steroid use, falls reported at baseline, and the total number of risk factors. Spine fractures depended only on T-score, odds ratio (OR) = 0.42 (0.23-0.76); hip fractures depended only on age, OR = 1.15 (1.07-1.24); forearm fractures depended only on age T-score, OR = 0.69 (0.51-0.92); and non-hip, non-spine on fall rate, OR = 1.86 (1.20-2.87). CONCLUSIONS: Fractures at various skeletal sites recorded in long-term follow-up in postmenopausal women were dependent on various risk factors. Multivariate analysis identified a single, dominant risk factor for each fracture location analysed.
INTRODUCTION: Our study endeavours to ascertain the plasma-derived long noncoding ribonucleic acids (lncRNA) and messenger RNA (mRNA) expression profiles through gene microarray analysis, aiming to elucidate their potent...INTRODUCTION: Our study endeavours to ascertain the plasma-derived long noncoding ribonucleic acids (lncRNA) and messenger RNA (mRNA) expression profiles through gene microarray analysis, aiming to elucidate their potential biological roles in the development and progression of diabetic cardiomyopathy (DCM), particularly with respect to myocardial fibrosis. MATERIAL AND METHODS: We conducted gene chip experiments to discern differences in lncRNA and mRNA expression profiles between diabetic cardiomyopathy and type 2 diabetes mellitus (T2DM). Differentially expressed mRNAs were subjected to functional enrichment analysis, thereby enabling the identification of key genes. Subsequently, we established an interaction network connecting lncRNAs with mRNAs. To validate myocardial fibrosis-related mRNAs, we further developed a rat model of diabetic cardiomyopathy. RESULTS: We identified 688 differentially expressed lncRNAs and 341 differentially expressed mRNAs, which were primarily enriched in creatine metabolism, small guanosine triphosphate hydrolase (GTPase)-mediated signal transduction, and fatty acid degradation processes. Our analyses revealed 8 core genes (SMD11, DRG1, RPS26, EIF2S1, UBE3A, CEBPZ, NUP153, and EMD) associated with diabetic cardiomyopathy. An investigation into the lncRNA-mRNA coexpression network underscored 4 lncRNAs (lnc-NEK10-3, lnc-KDM4A-2, lnc-PCYOX1-3, and lnc-CDCP2-1) as significantly linked to differentially expressed fibrosis-associated mRNAs. The expression levels of transmembrane protein 173 (TMEM173) and toll-like receptor 7 (TLR7) were found to be significantly higher in DCM compared to normal controls, whereas cathepsin L1 (CTSL) and forkhead box O3 (FOXO3) displayed significantly lower expression levels relative to those of normal controls. CONCLUSIONS: Our study disclosed a subset of lncRNAs and mRNAs that are implicated in diabetic cardiomyopathy and myocardial fibrosis, thereby presenting themselves as promising biomarkers and therapeutic targets for the management of both diabetic cardiomyopathy and myocardial fibrosis.
INTRODUCTION: With an increasing incidence of differentiated thyroid cancer (DTC) diagnosis, questions emerge about the optimal duration of follow-up for detecting recurrent disease and its outcomes. The objective of thi...INTRODUCTION: With an increasing incidence of differentiated thyroid cancer (DTC) diagnosis, questions emerge about the optimal duration of follow-up for detecting recurrent disease and its outcomes. The objective of this retrospective research was to assess the clinical course of differentiated thyroid cancer after radioiodine adjuvant treatment in patients monitored over an extended period. Special attention was paid to the analysis of the time from treatment to recurrence. We also assessed patient outcomes after recurrence. MATERIAL AND METHODS: A total of 650 patients with DTC after total/near-total thyroidectomy and adjuvant radioiodine post-recombinant human thyrotropin (post-rhTSH) stimulation were evaluated. All patients were followed up with neck ultrasound, serum thyroid-stimulating hormone (TSH), thyroglobulin (Tg), and antithyroglobulin antibody (anti-Tg) measurements at intervals of 6 to 18 months. Only structural recurrences were considered. They were defined as locoregional recurrence confirmed by biopsy or distant metastases [confirmed by computed tomography (CT) or magnetic resonance imaging (MRI), or abnormal foci on radioiodine scintigraphy or 18F-gluorodeoxyglucose positron emission tomography [18 F] FDG-PET scan], regardless of thyroglobulin (Tg) or anti-Tg levels. RESULTS: The median follow-up was 12 years (5-15.5). Structural recurrence was observed in 47 out of 650 patients (7%). All but 3 locoregional recurrences were suitable for surgery. The median time to structural recurrence was 16 months, with only 9 (1.4%) patients presenting with recurrence after more than 60 months. At the time of the database closure, 601 patients (92%) had an excellent response, including 20 out of 47 (42%) patients with structural recurrence. Eighty-one out of 650 patients had died (12.5%) before the database closure. The median age at the last follow-up of the patients who died was 72 years (range 20-88). A second recurrence was diagnosed in 10 out of 650 patients (1.5%), corresponding to 21% (10 out of 47) of patients who had already experienced a recurrence. The median time from radioiodine (RAI) therapy to the second structural recurrence was 108 months. CONCLUSIONS: Structural recurrences in DTC are uncommon, with most patients showing a favourable response to treatment. Improved understanding of recurrence timing may define the duration of patient surveillance at reference centres that can be safely discontinued after 5 years in low- and intermediate-risk groups, as indicated in our study.
Type 2 diabetes mellitus (T2DM) represents a chronic metabolic disorder, constituting over 90% of all diabetes cases. Its primary characteristics include insulin deficiency and insulin resistance. The aetiology of T2DM i...Type 2 diabetes mellitus (T2DM) represents a chronic metabolic disorder, constituting over 90% of all diabetes cases. Its primary characteristics include insulin deficiency and insulin resistance. The aetiology of T2DM is complex, which is attributed to a convergence of genetic and environmental factors. Moreover, it can engender various complications such as diabetes retinopathy, diabetes nephropathy, and diabetes neuropathy. T2DM cannot be cured fundamentally, it can only delay the development of the disease by controlling the blood sugar level. If the blood sugar is at a high level for a long time, it will aggravate the disease progress, and even lead to death in serious cases. Therefore, understanding the pathogenesis of diabetes, early detection, and intervention are the main means of treatment. S-nitrosylation (SNO), a post-translational modification of proteins based on redox, possesses the capacity to regulate a variety of physiological and pathological processes, and it is also involved in the occurrence and development of T2DM. However, the relationship between the dysregulation of SNO homeostasis and the occurrence of diabetes is not fully understood. This article reviews the correlation between SNO and T2DM, elucidating the mechanism by which SNO contributes to T2DM, encompassing diminishing insulin secretion, inducing insulin resistance, and affecting glucokinase activity. Understanding the correlation between SNO and T2DM provides a new research direction for the pathogenesis and treatment targets of diabetes.
Autoimmune thyroiditis (AIT) is due to an autoimmune process that destroys thyrocytes, leading to hormonal disorders. AIT is more common in women, and the aetiology is multifactorial. The destruction of thyroid cells may...Autoimmune thyroiditis (AIT) is due to an autoimmune process that destroys thyrocytes, leading to hormonal disorders. AIT is more common in women, and the aetiology is multifactorial. The destruction of thyroid cells may release free thyroid hormones into the bloodstream, causing hyperthyroid symptoms. With further destruction of thyroid cells, patients develop euthyroidism and eventually chronic hypothyroidism. The diagnosis of AIT is based on clinical symptoms, positive anti-thyroid antibodies, ultrasound, and histological features. The main goal of treatment is correcting hormonal disorders and achieving euthyroidism. Treatment of AIT involves replacing thyroid hormone deficiency with the use of synthetic hormones. Prophylactic levothyroxine (L-T4) treatment of euthyroid patients with AIT may reduce both serological and cellular markers of autoimmunisation. Attention should be paid to the starting dose of L-T4, potential drug interactions, and drug formulation. A follow-up should be planned to determine the optimal dose. The authors highlighted that a healthy lifestyle and supplementing selected vitamins and microelements appropriately are essential. In selected clinical conditions, thyroidectomy should be considered. There are also alternative therapeutic strategies, such as herbal medicine and acupuncture, but their effectiveness has yet to be conclusively confirmed in research studies. Monitoring the thyroid gland enlargement and the possibility of developing nodular goitre is integral to patient care over AIT patients. In conclusion, treating AIT is complex, involving thyroid hormone replacement therapy, taking care of a healthy diet and lifestyle, and proper supplementation. It requires an individual approach. Regular follow-up is necessary to control the disease and minimise its effects.
INTRODUCTION: In previous studies on thyroid hormones and frailty, most of the target population were elderly, and there were relatively few studies on elderly patients with coronary heart disease (CHD). Inflammation, ox...INTRODUCTION: In previous studies on thyroid hormones and frailty, most of the target population were elderly, and there were relatively few studies on elderly patients with coronary heart disease (CHD). Inflammation, oxidative stress, and haemodynamic instability in cardiovascular disease (CVD) can influence fluctuations in thyroid hormone (TH) levels and increase the incidence of frailty. The purpose of the present study was to explore the effect of TH on the risk of frailty in elderly patients with CHD. MATERIAL AND METHODS: The Fried scale was used to assess the frailty of participants. The predictive value of TH for frailty was determined using the patient's operating characteristic curve. Multivariate logistic regression model was utilised to analyse the relationship between TH and frailty. RESULTS: A total of 277 elderly patients with CHD were included in the study, of whom 29.96% were in a state of frailty. Free triiodothyronine (FT3)/free thyroxine (FT4) predicted frailty with the largest area under the curve of 0.634. Unordered multinomial logistic regression analysis showed that a lower T3 level was a risk factor for pre-frailty (p < 0.05). Lower levels of T3, FT3, and FT3/FT4 were risk factors for frailty (p < 0.05) after adjusting for demographic variables and blood indexes. CONCLUSION: The predictive value of FT3/FT4 for frailty was more accurate than that of a single index. Moreover, T3 ≤ 1.095 nmol/L, FT3 ≤ 4.085 pmol/L, and FT3/FT4 ≤ 0.336 were shown to be the influencing factors of frailty, while T3 ≤ 1.095 nmol/L is an independent risk factor pre-frailty. Clinicians should focus on timely identification of the risk of frailty in order to improve patient quality of life and to reduce the risk of complications.
BACKGROUND: Globally, there has been a steady increase in the prevalence of type 2 diabetes, and the risk of cardiovascular disease has increased. The relationship between diabetes and the incidence of cardiovascular dis...BACKGROUND: Globally, there has been a steady increase in the prevalence of type 2 diabetes, and the risk of cardiovascular disease has increased. The relationship between diabetes and the incidence of cardiovascular disease (CVD) at different blood pressure, glycated haemoglobin A1c (HbA1c), and lipid levels remains uncertain. This study aimed to investigate these associations within a population-based cohort. MATERIAL AND METHODS: We analysed data from the Guiyang subcentre of the China Cardiometabolic Disease and Cancer Cohort Study, which enrolled participants aged 40 years and older between 2011 and 2012. Subsequently, a follow-up visit was conducted during 2014-2016 to assess incident CVD events. RESULTS: The analysis included a cohort of 7197 adults, of whom 590 were diagnosed with diabetes. Among all the participants, the CVD events linked to diabetes had a multivariable adjusted hazard ratio of 2.37 [95% confidence intervals (CI): 1.38-4.08]. Patients with diabetes had a greater risk of experiencing CVD events if they had high blood pressure [hazard ratios (HR): 1.24, 95% CI: 1.39-4.21] and high lipid levels (HR: 2.19, 95% CI: 1.29-3.70) compared to people with normal blood pressure (HR: 1.23, 95% CI: 0.54-2.82) and lipid levels (HR: 1.26, 95% CI: 0.47-3.41). CONCLUSIONS: Our analysis revealed a significant association between diabetes and an increased risk of subsequent CVD events, which can be mitigated through optimal management of the metabolic profile of cardiovascular risk factors.
Anaplastic thyroid carcinoma (ATC) is reckoned as an infrequent but extremely advanced neoplasm of the endocrine system. Diaphanous-related formin 3 (DIAPH3) has been extensively implicated in carcinogenic events, but it...Anaplastic thyroid carcinoma (ATC) is reckoned as an infrequent but extremely advanced neoplasm of the endocrine system. Diaphanous-related formin 3 (DIAPH3) has been extensively implicated in carcinogenic events, but it has not been introduced in ATC. Herein, the role of DAPIH3 and the interrelated functional mechanism are characterised in ATC. The Gene Expression Omnibus (GEO) database was checked for differential DIAPH3 expression in ATC samples and noncancerous samples. Western blotting examined DIAPH3 and forkhead box M1 (FOXM1) expression in ATC cells. In vitro cell counting kit 8 (CCK-8) method, 5-ethynyl-2'-deoxyuridine (EdU) incorporation, Scratch, Matrigel invasion, and terminal-deoxynucleotidyl transferase mediated nick end labelling (TUNEL) assays were used to assess the potential of cells to proliferate, migrate, and invade as well as the cellular apoptotic rate. Co-IP was applied to access DIAPH3-FOXM1 protein interaction. Western blotting also disclosed the expression of proteins associated with apoptosis and Wnt/β-catenin signalling. DIAPH3 was hyper-expressed in papillary cell carcinoma (PTC) tissues and cells. Depleting DIAPH3 strongly eliminated the proliferative, migratory, as well as invasive capabilities of PTC cells while intensifying the apoptotic ability. FOXM1 also harboured elevated expression in PTC cells. FOXM1 was the binding partner with DIAPH3, and the 2 were positively correlated. FOXM1 upregulation again exacerbated the potentials to proliferate, migrate, and invade but it repressed the apoptotic rate of DIAPH3-depleted cells. Furthermore, loss of DIAPH3 downregulated FOXM1 to block Wnt/b-catenin signalling in PTC cells. Combined with these findings, DIAPH3 might favour the aggressive advancement of ATC and motivate the Wnt/β-catenin signalling via binding with FOXM1.
INTRODUCTION: Thyroid cancer is a commonly occurring malignant tumour within the endocrine system, the incidence of which has been increasing steadily in our country. It has been the focus and direction of research in re...INTRODUCTION: Thyroid cancer is a commonly occurring malignant tumour within the endocrine system, the incidence of which has been increasing steadily in our country. It has been the focus and direction of research in recent decades to continuously explore the diagnostic markers and molecular mechanisms of thyroid cancer and provide new possibilities for the healing of patients. In this study, lncRNA DHRS4-AS1 was identified as the research target, and the regulatory function of abnormal expression of DHRS4-AS1 on thyroid cancer was discussed. MATERIAL AND METHODS: Thyroid cancer (116) and non-cancer normal (82) tissue samples were collected in this paper, and the expression of DHRS4-AS1 and miR-222-3p in tissues and cells were evaluated by RT-qPCR. CCK-8 and flow cytometry were used to detect cell survival status. The mechanism of DHRS4-AS1 sponge miR-222-3p was analysed by dual-luciferase reporter gene detection. RESULTS: In the present study, DHRS4-AS1 was down-regulated in both thyroid tissue and cell samples, while miR-222-3p expression was elevated. The ROC curve reflected the diagnostic value of DHRS4-AS1 in thyroid cancer [area under the curve (AUC) = 0.887, sensitivity = 76.7%, specificity = 95.1%]. DHRS4-AS1 regulates the development of thyroid cancer by targeting miR-222-3p. In addition, in vitro experiments demonstrated that overexpression of DHRS4-AS1 (pcDNA3.1-DHRS4-AS1) inhibited the proliferation of thyroid cancer cells and promoted cell apoptosis, while down-regulating the level of miR-222-3p. CONCLUSIONS: DHRS4-AS1 acts as a miR-222-3p sponge in thyroid cancer, and overexpression of DHRS4 AS1 down-regulates cell proliferation and promotes cell apoptosis. These findings demonstrate the potential of DHRS4-AS1 as a diagnostic factor for thyroid cancer.
Type 1 diabetes mellitus (T1DM) is characterized by an increased prevalence of polycystic ovary syndrome (PCOS) with its negative metabolic consequences, including increased cardiovascular risk. Both diseases affect pati...Type 1 diabetes mellitus (T1DM) is characterized by an increased prevalence of polycystic ovary syndrome (PCOS) with its negative metabolic consequences, including increased cardiovascular risk. Both diseases affect patients, significantly deteriorating the quality of life. During the treatment of patients with T1DM and PCOS, lifestyle modification and increased physical activity resulting in weight reduction should always be recommended. Pharmacological treatment should be applied in accordance with the current standards. In most of these patients metformin alone or with combined oral contraceptive pills could be considered for cycle regulation. In obese patients with T1DM and PCOS glucagon-like peptide-1 receptor agonists (GLP-1 Ras) (liraglutide, semaglutide) and dual glucose-dependent insulinotropic polypeptides (GIP)/GLP-1 RAs (tirzepatide) are regarded as a safe approach. Anti-androgens could also be considered especially to treat hirsutism and hyperandrogenism in women with PCOS. There are relatively limited evidence on anti-androgens in PCOS and we should consider use them in only selected cases. Some other substances may have a positive effect on patients with T1DM and PCOS include inositol, alpha-lipoic acid, folic acid, vitamins (B1, B6, B12, D, K, E, A), chromium and selenium compounds, as well as omega-3 fatty acids. The gut microbiome is also considered as a critical modulator of the predisposition to PCOS and T1DM and may be the future goal of the treatment. The proper treatment of PCOS will translate into a reduction in the severity of typical symptoms and also into the improvement in the metabolic control of diabetes and the patients' quality of life.
There are substantial data confirming the association between autoimmune disorders, including connective tissue diseases (CTDs), and an increased risk of thyroid malignancy. CTDs and thyroid cancer may co-exist as 2 sepa...There are substantial data confirming the association between autoimmune disorders, including connective tissue diseases (CTDs), and an increased risk of thyroid malignancy. CTDs and thyroid cancer may co-exist as 2 separate diseases because of their relatively high incidence rates in the population. They can arise from each other due to the increased risk of thyroid cancer in patients with idiopathic inflammatory myositis, rheumatoid arthritis, systemic sclerosis, primary Sjögren's syndrome, and systemic lupus erythematosus. Moreover, in some scarce cases, CTDs may act as the paraneoplastic syndromes of thyroid cancer. The presence of CTDs may impact the diagnostic process, especially distorting the results of imaging tests or falsely indicating the increase of thyroglobulin or calcitonin. Finally, TSH suppression is a crucial element of the treatment of differentiated thyroid cancer, which may decrease bone mineral density and increase the risk of osteoporosis by accelerating bone turnover and shortening the bone remodeling cycle. The aim of this review is to emphasise the vital aspects of this interrelationship. The authors discuss this phenomenon aiming at the explanation of possible linking mechanisms. The impact of selected CTDs on thyroid cancer management is presented, as well as the possible effects of cancer therapy on skeletal health.