INTRODUCTION: Hyperglycemia-induced endothelial injury is a major contributor to diabetic vasculopathy. While sodium-glucose transporter2 (SGLT2) in renal proximal tubules plays a critical role in diabetes, its expressio...INTRODUCTION: Hyperglycemia-induced endothelial injury is a major contributor to diabetic vasculopathy. While sodium-glucose transporter2 (SGLT2) in renal proximal tubules plays a critical role in diabetes, its expression and function in kidney endothelial cells, particularly regarding sex-specific disease progression, remain unclear. MATERIAL AND METHODS: SGLT2 expression in kidney endothelial cells was examined in male streptozotocin (STZ)-induced diabetic miceusing immunostaining. In human umbilical vein endothelial cells (HUVECs) treated with high glucose, we investigated the impact ofSGLT2 on mitochondrial dynamics following empagliflozin treatment. Molecular mechanisms were elucidated using qRT-PCR and Westernblot. Therapeutic efficacy was evaluated by histological analysis. RESULTS: SGLT2 was significantly upregulated in kidney endothelial cells of diabetic male mice. High glucose increased SGLT2 expressionin HUVECs, promoting mitochondrial fission and reducing fusion. Both SGLT2 siRNA knockdown and empagliflozin treatment markedlyenhanced mitochondrial fusion. Mechanistically, empagliflozin activated AMPK, increasing KLF4 expression and promoting mitochondrialfusion, thereby protecting against endothelial dysfunction. AMPK inhibition abrogated empagliflozin's protective effects in diabetic mice. CONCLUSIONS: SGLT2 critically regulates endothelial dysfunction under hyperglycemic conditions through the AMPK/KLF4-mitochondrialdynamics axis. Empagliflozin protects both proximal tubules and kidney endothelial cells in diabetes. Given accelerated diabetic kidneydisease progression in males, our male mouse model findings provide clinically relevant insights into sex-specific therapeutic responsesto SGLT2 inhibitors in diabetic vasculopathy.
Increased body mass index and excessive lipid accumulation are associated with enhanced production of toxic lipid species and impairedoxidation of free fatty acids (FFAs), a phenomenon defined as lipotoxicity. It is an i...Increased body mass index and excessive lipid accumulation are associated with enhanced production of toxic lipid species and impairedoxidation of free fatty acids (FFAs), a phenomenon defined as lipotoxicity. It is an important predictor of etabolic disorders such astype 2 diabetes (T2D). Increased lipid accumulation leads to decreased glucose uptake in skeletal muscle and enhanced hepatic glucoseproduction. Thus, ectopic fat accumulation impairs insulin signalling and decreases insulin sensitivity (IS). Scientific data demonstratethat glucagon-like peptide-1 receptor agonists (GLP-1 RAs) can improve IS and decrease lipid accumulation in peripheral tissues mainlythrough weight loss. However, experimental studies indicate that GLP-1 RAs exert direct effects on glucose and lipid metabolic pathways,although the precise mechanisms remain incompletely understood. GLP-1 RAs may directly modulate fatty acid β-oxidation, lipogenesis,and 5'-AMP-activated protein kinase (AMPK) phosphorylation. In this review, we discuss the mechanisms by which liraglutide and subcutaneoussemaglutide affect IS and lipid accumulation in key insulin-responsive tissues.
Tarnowska JA, Szydzik F, Żegleń B
… +6 more, Zalewska E, Berendt-Obołończyk M, Kaniuka-Jakubowska S, Kunc M, Kufel-Grabowska J, Świątkowska-Stodulska R
INTRODUCTION: Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine disorder in which hyperandrogenism represents a centralpathophysiological feature. Increasing attention has been directed toward chronic inflamm...INTRODUCTION: Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine disorder in which hyperandrogenism represents a centralpathophysiological feature. Increasing attention has been directed toward chronic inflammatory factors that may modulate androgenexcess. Helicobacter pylori (H. pylori) infection is a prevalent chronic bacterial infection associated with systemic low-grade inflammation.However, its potential relationship with androgen-related hormonal parameters in PCOS remains poorly explored. MATERIAL AND METHODS: This observational mini case series included seven women with PCOS diagnosed according to the Rotterdam criteriaand confirmed active H. pylori infection. Hormonal parameters including total testosterone, androstenedione, dehydroepiandrosteronesulfate (DHEAS), sex hormone-binding globulin (SHBG), anti-Müllerian hormone (AMH), and free androgen index (FAI) were assessedduring active infection and after confirmed eradication. No hormonal contraception, antiandrogens, metformin, incretin-based therapies,or inositol supplements were used during the study period. RESULTS: Following successful H. pylori eradication, consistent changes in androgen-related parameters were observed. Median DHEAS,androstenedione, and total testosterone concentrations decreased, while SHBG levels increased. Consequently, the free androgen indexdecreased in all patients. AMH levels showed a downward trend after eradication. Due to the descriptive nature of the study, no inferentialstatistical analyses were performed. CONCLUSIONS: In this observational case series, H. pylori eradication was associated with coherent changes in androgen-related hormonal parameters and reduced androgen bioavailability in women with PCOS. Although causality cannot be established, these findings suggestthat chronic infection-related inflammation may influence the androgenic milieu in PCOS.
INTRODUCTION: MicroRNAs (miRNAs) play critical roles in tumorigenesis and malignant transformation. Studies indicate aberrant expressionof miR-4260 in various cancers. However, its specific function and underlying molecu...INTRODUCTION: MicroRNAs (miRNAs) play critical roles in tumorigenesis and malignant transformation. Studies indicate aberrant expressionof miR-4260 in various cancers. However, its specific function and underlying molecular mechanisms in thyroid cancer (TC) remainpoorly understood. MATERIAL AND METHODS: Paired tumor and adjacent non-tumor tissues were collected from a cohort of 120 TC patients undergoing surgicalresection. Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) quantified miR-4260 expression in clinical specimensand cell lines. The prognostic value of miR-4260 expression was evaluated using Kaplan-Meier survival analysis and multivariate Coxproportional hazards regression. The functional impact of miR-4260 on TC cell proliferation, migration, and invasion was assessed usingcell transfection, cell counting kit 8 (CCK-8) assays, and Transwell migration/invasion assays. The regulatory interaction between miR-4260and its potential target gene was validated by dual-luciferase reporter assay. RESULTS: RT-qPCR analysis revealed significantly elevated miR-4260 expression in TC tissues compared to matched non-tumor tissues. High miR-4260 expression correlated significantly with larger tumor size (p = 0.035), deeper invasion depth (p = 0.038), advanced tumor-node-metastasis (TNM) stage (p = 0.022), and lymph node metastasis (LNM) (p = 0.025) compared to low expression. MultivariateCox analysis identified high miR-4260 expression as an independent predictor of poor prognosis [hazard ratio (HR) = 3.398, 95% confidenceinterval (CI): 1.559-7.406, p = 0.002]. Functional experiments demonstrated that inhibiting miR-4260 expression significantly attenuatedthe proliferative and invasive capacities of TC cells. Dual-luciferase assays validated ANK2 as a direct miR-4260 target. RT-qPCR quantification revealed significantly antagonistic expression patterns between ANK2 and miR-4260 in thyroid carcinoma specimens. Rescueexperiments further revealed that miR-4260 modulates the malignant phenotype of TC cells by negatively regulating ANK2, indicating their cooperative involvement in TC progression. CONCLUSIONS: miR-4260 is critically implicated in TC advancement and unfavorable patient outcomes, establishing its bifunctional value as a clinically significant prognostic indicator and viable therapeutic candidate.
INTRODUCTION: Prolactin has been shown to play an important role in the regulation of glucose metabolism. The present study aimed toevaluate incretin hormones in patients with prolactinoma. MATERIAL AND METHODS: The stud...INTRODUCTION: Prolactin has been shown to play an important role in the regulation of glucose metabolism. The present study aimed toevaluate incretin hormones in patients with prolactinoma. MATERIAL AND METHODS: The study included 13 patients with prolactinoma without a history of diabetes and in 13 healthy volunteers.All participants underwent a 75-g oral glucose tolerance test (OGTT). Serum glucose, insulin, glucagon-like peptide-1 (GLP-1), and glucose-dependent insulinotropic polypeptide (GIP) were measured at 0, 30, 60, 90, and 120 minutes. RESULTS: Serum glucose and insulin levels at baseline and during the OGTT were similar in both groups (p > 0.05). GLP-1 levels, including baseline values, area under the curve (AUC), and all time points during OGTT, were also comparable between the groups (p > 0.05).In contrast, baseline GIP (p = 0.024), AUC (p = 0.011), and GIP levels at 30, 90, and 120 minutes were significantly lower in patients withprolactinoma (p = 0.006, p = 0.015, and p = 0.035, respectively). CONCLUSIONS: These findings suggest that incretins may play a role in the mechanisms underlying glucose metabolism disorders in patientswith hyperprolactinemia due to prolactinoma. Larger studies are needed to confirm this potential association.
INTRODUCTION: Papillary thyroid carcinoma (PTC) with metastasis has a poor prognosis and requires effective prognostic markers. Becauselong non-coding ribonucleic acid (lncRNA) HCG4 is abnormally expressed in thyroid can...INTRODUCTION: Papillary thyroid carcinoma (PTC) with metastasis has a poor prognosis and requires effective prognostic markers. Becauselong non-coding ribonucleic acid (lncRNA) HCG4 is abnormally expressed in thyroid cancer, this study investigated its prognostic valuefor PTC and its regulatory mechanisms. MATERIAL AND METHODS: This study included 128 patients with PTC. The prognostic value of HCG4 was assessed using Kaplan-Meier curves.COX analysis was used to identify prognostic factors affecting PTC. HCG4 and miR-146b-5p levels in tissues and cells were assessed usingreal-time quantitative reverse transcription polymerase chain reaction (RT-qPCR). Cell proliferation was detected using a cell counting kit(CCK-8 kit). Cell invasion and migration were assessed using a Transwell assay. The binding relationship between HCG4 and miR-146b-5pwas detected using dual-luciferase reporter (DLR). RESULTS: HCG4 levels were reduced in PTC tissues, and cells compared with normal tissues, while miR-146b-5p levels were increased. PTCpatients with low HCG4 levels demonstrated lower 5-year survival rates, and HCG4 also serves as an independent protective prognosticfactor for PTC. HCG4 negatively regulates the level of miR-146b-5p. HCG4 overexpression inhibits cell proliferation, invasion, and migrationabilities of the cells. These abilities were restored by increasing the level of miR-146b-5p. Therefore, increasing HCG4 could reducethe level of miR-146b-5p, thereby alleviating PTC development. CONCLUSIONS: HCG4 demonstrates favorable prognostic value. Overexpression of HCG4 can reduce the level of miR-146b-5p, inhibit the survival rate and invasiveness of PTC cells, and thereby potentially alleviate the progression of PTC.
INTRODUCTION: The relationship between metabolic dysfunction-associated steatotic liver disease (MASLD) and overweight/obesity, as well as prediabetes or type 2 diabetes mellitus (T2DM), is complex. It is known that thes...INTRODUCTION: The relationship between metabolic dysfunction-associated steatotic liver disease (MASLD) and overweight/obesity, as well as prediabetes or type 2 diabetes mellitus (T2DM), is complex. It is known that these conditions increase the risk of MASLD. The aim of this study was to assess the influence of body mass index (BMI), sex, and prediabetes/T2DM status on the prevalence of MASLD. MATERIAL AND METHODS: The study included patients from The Polish Gallstone Surgery Registry, and MASLD was diagnosed according to current criteria. RESULTS: Among the 3392 participants, 859 (25.3%) had normal body mass, 1302 (38.4%) were overweight, and 1231 (36.3%) had obesity. MASLD was diagnosed in 828 patients (24.4%), including 93 (11%) with normal body mass, 280 (21.4%) who were overweight, and 455 (36.9%) with obesity, p < 0.001. The odds ratios (ORs) for MASLD increased from overweight [OR = 2.30, 95% confidence interval (CI): 1.62-3.30] to obesity class I (OR = 4.50, 95% CI: 3.16-6.50), obesity class II (OR = 7.91, 95% CI: 5.11-12.33), and obesity class III (OR = 12.74, 95% CI: 7.11-22.93), with p < 0.001 for all categories. The risk of MASLD occurrence increased with BMI in obesity class III and was OR = 4.70, 95% CI: 2.08-10.64, p = 0.02 in males and OR = 5.32, 95% CI: 2.91-9.71, p < 0.001 in females. For patients without T2DM or prediabetes, the risk of MASLD in obesity class III was nearly 9-fold higher [hazard ratio (HR): 8.77, 95% CI: 5.28-14.58, p = 0.001], compared with HR = 2.85, 95% CI: 1.43-5.68, p = 0.003 for those with T2DM or prediabetes. CONCLUSIONS: A significant association was demonstrated between the prevalence of MASLD and increasing BMI, and this relationship was more pronounced in women. T2DM/prediabetes had a predominant influence on the occurrence of MASLD. Both patients with excess body weight and, especially, patients with T2DM/prediabetes require mandatory MASLD diagnostics.
Berardinelli-Seip syndrome, also known as congenital generalized lipodystrophy (CGL), is a rare genetic disorder characterized by lipoatrophy, acromegaloid features, hyperinsulinemia, hypertriglyceridemia, and hepatic st...Berardinelli-Seip syndrome, also known as congenital generalized lipodystrophy (CGL), is a rare genetic disorder characterized by lipoatrophy, acromegaloid features, hyperinsulinemia, hypertriglyceridemia, and hepatic steatosis. With estimated prevalence 1 in every 10,000,000 births, CGL challenges medical specialists to seek better ways for early diagnosis of the disease. Despite its rarity, the condition is associated with severe metabolic and cardiovascular complications, leading to significant morbidity and reduced life expectancy. Advances in molecular genetics have identified mutations in AGPAT2, BSCL2, CAV1, and PTRF, which provide important insights into adipose tissue biology and systemic metabolism. Early recognition and genetic confirmation are crucial to initiate timely interventions, including lifestyle modification, insulin sensitizers, and lipid-lowering therapies including metreleptin therapy in indicated cases. Two illustrative cases are presented, reflecting our experience with the clinical variability, genetic findings, and therapeutic strategies in CGL as well as highlighting the importance of comprehensive care and emerging therapies.
Hypoparathyroidism (HypoPT) remains the last "classic" endocrine deficiency hormone disorder not routinely treated with hormone replacement. In November 2023, European Medicines Agency (EMA), and in August 2024, Food and...Hypoparathyroidism (HypoPT) remains the last "classic" endocrine deficiency hormone disorder not routinely treated with hormone replacement. In November 2023, European Medicines Agency (EMA), and in August 2024, Food and Drug Administration (FDA) registered a new parathyroid hormone analogue: palopegteryparatide (TransCon PTH; YORVIPATH®) for the treatment of selected cases of hypoparathyroidism. As the Polish Society of Endocrinology Expert Panel, we recommend that parathyroid hormone (PTH) replacement therapy should be considered for HypoPT patients in whom conventional therapy is insufficient or poorly tolerated. PTH replacement therapy offers a more physiologic approach to treating HypoPT than conventional therapy. Palopegteriparatide can lead to eucalcemia, more effectively than conventional treatment, lowers serum phosphate and urinary calcium, and improves renal function and quality of life.
INTRODUCTION: Hypercalcemia is a potentially life-threatening electrolyte disorder with diverse etiologies and clinical manifestations, frequently encountered in hospitalized patients. Understanding its prevalence, cause...INTRODUCTION: Hypercalcemia is a potentially life-threatening electrolyte disorder with diverse etiologies and clinical manifestations, frequently encountered in hospitalized patients. Understanding its prevalence, causes, and associated outcomes in the inpatient setting is crucial for improving patient management and prognosis. The objectives were to determine the prevalence, etiological distribution, clinical and demographic characteristics, comorbidities, laboratory features, and mortality risk factors of hypercalcemia among patients admitted to an internal medicine clinic in a tertiary university hospital. MATERIAL AND METHODS: This retrospective, observational cohort study included adults (≥ 18 years) hospitalized with hypercalcemia (corrected calcium ≥ 10.2 mg/dL, confirmed twice at least 24 hours apart) between January 2022 and January 2024. Hypercalcemia severity was classified as mild, moderate, or severe. Etiological categories included malignancy-associated, endocrine-related, vitamin D-mediated, other, and undetermined. Demographics, comorbidities, laboratory parameters, treatments, and outcomes were recorded. Univariate and multivariate analyses were performed to identify mortality risk factors. RESULTS: Among 3,157 admissions, 190 patients (prevalence 6%) had confirmed persistent hypercalcemia (mean age 72.3 ± 13.1 years; 61.6% female). Malignancy was the leading cause (49.5%), followed by other causes (24.7%), undetermined (15.8%), endocrine (8.4%), and vitamin D-mediated (1.6%). Severe hypercalcemia (11.6%) was predominantly associated with malignancy. Overall in-hospital mortality was 24.2%, with male sex, malignancy, solid tumors, elevated aspartate aminotransferase (AST), hypoalbuminemia, and age 65-80 years independently associated with mortality. Survival was significantly worse in malignancy-related cases. The optimal parathyroid hormone (PTH) threshold for predicting malignancy was identified as ≤ 12.61 pg/mL. This cut-off demonstrated a sensitivity of 71.4% and a specificity of 91.3%. CONCLUSIONS: Hypercalcemia in hospitalized patients is predominantly associated with malignancy and advanced age, and is linked with high mortality. Early identification of risk factors and etiology-driven management are critical for improving outcomes.
INTRODUCTION: The aim of the study was to investigate the value of anti-Müllerian hormone (AMH) as a predictor of implantation and/or clinical pregnancy rate per started intracytoplasmic sperm injection (ICSI) cycle in a...INTRODUCTION: The aim of the study was to investigate the value of anti-Müllerian hormone (AMH) as a predictor of implantation and/or clinical pregnancy rate per started intracytoplasmic sperm injection (ICSI) cycle in a young patient population with decreased versus normal ovarian reserve. MATERIAL AND METHODS: This retrospective case-control cohort study utilized data extracted from participants' electronic medical records. Patients were subsequently grouped into AMH < 1.1 [decreased ovarian reserve group (DOR)] and AMH ≥ 1.1 [normal ovarian reserve group (NOR)]. The groups were organized to be age-compatible to evaluate specifically the role of AMH in the outcomes. Prediction performance was examined with receiver operating characteristic (ROC) curves. RESULTS: A total of 716 women were analyzed, including 298 (41.6%) with diminished ovarian reserve (DOR) and 418 age-matched women with normal ovarian reserve (NOR) serving as controls (58.4%). AMH levels below 1.1 ng/mL and 0.47 ng/mL were associated with an increased likelihood of embryo transfer (ET) cancellation. Among women who proceeded to ET, higher AMH levels were associated with positive implantation (all p < 0.001). An AMH cut-off value of ≥ 1.1 ng/mL significantly predicted clinical pregnancy and live birth, and overall AMH levels were significantly higher in women who achieved ET, implantation, clinical pregnancy, and live birth than in those who did not (all p < 0.001). CONCLUSIONS: Higher AMH levels were associated with better ET, implantation, and clinical pregnancy, especially in NOR patients; however, we also showed that the rates of pregnancy outcomes after the development of a transferable embryo in younger cases are similar to those in cases with NOR. Low but not severely diminished AMH levels in young patients may not necessarily indicate poor oocyte quality.
INTRODUCTION: Gout has placed a significant burden on healthcare expenditures and society in recent decades. The systemic immune-inflammation index (SII) and systemic inflammatory response index (SIRI) have been used as...INTRODUCTION: Gout has placed a significant burden on healthcare expenditures and society in recent decades. The systemic immune-inflammation index (SII) and systemic inflammatory response index (SIRI) have been used as new non-specific inflammatory markers. This study aims to investigate the possible association between these markers and gout. MATERIAL AND METHODS: Gout patients and non-gout participants were recruited from our hospital and the 2007-2016 National Health and Nutrition Examination Survey (NHANES) database. The differences in clinical data, SII, and SIRI between the two groups were compared. Logistic regression analysis was used to examine the relationship between each variable and the occurrence of gout. After adjusting for confounding factors, the relationship between multiple inflammatory indices and gout risk was further evaluated and visualized by the restricted cubic spline (RCS) model. RESULTS: There were significant differences in gender, age, education level, body mass index, smoking status, alcohol consumption, hypertension, and diabetes between gout patients and healthy controls (p < 0.05). Male patients, older age, married, low education level, smoking, drinking, diabetes, high neutrophil count, high monocyte count, high platelet count, and high Systemic Immune-Inflammation Index (SII) and Systemic Inflammation Response Index (SIRI) index are risk factors for gout. Spearman correlation analysis revealed that lymphocyte count and platelet count were negatively correlated with serum uric acid levels, whereas neutrophil count, monocyte count, and SIRI index were positively correlated with serum uric acid levels. The results were further validated through analysis of the NHANES database. CONCLUSIONS: Our findings suggest that SII and SIRI are positively correlated with a high risk of gout and can be used as novel inflammatory markers for gout.