INTRODUCTION: One of the core pathological features of type 2 diabetes mellitus (T2DM) is pancreatic β-cell dysfunction. MicroRNAs, askey regulatory molecules, have emerged as pivotal post-transcriptional regulators of β...INTRODUCTION: One of the core pathological features of type 2 diabetes mellitus (T2DM) is pancreatic β-cell dysfunction. MicroRNAs, askey regulatory molecules, have emerged as pivotal post-transcriptional regulators of β-cell homeostasis, but their specific regulatorymechanisms require further clarification. This study aimed to investigate the expression characteristics and diagnostic value of miR-506-5pin T2DM and its regulatory mechanism in pancreatic β-cell function. MATERIAL AND METHODS: A total of 45 healthy controls and 48 patients with T2DM were enrolled. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to quantify peripheral blood miR-506-5p and p21-activated kinase 1 (PAK1) levels, and theircorrelations with clinical indicators and diagnostic efficacy were analyzed. Using INS-1 cells as the model, overexpression or knockdown ofmiR-506-5p was achieved by transfecting miR-506-5p mimic/inhibitor. Combined with a dual-luciferase reporter gene assay and functionalrescue experiment, the target molecule and regulatory role of miR-506-5p were clarified. RESULTS: miR-506-5p expression was significantly elevated in patients with T2DM, whereas PAK1 expression was significantly decreased. The area under the curve (AUC) of miR-506-5p for diagnosing T2DM was 0.904, and it was positively correlated with fasting plasmaglucose (FPG) and glycated hemoglobin (HbA1c). Cell experiment results showed that high glucose could upregulate miR-506-5p expression. Overexpression of miR-506-5p suppressed pancreatic β-cell viability, promoted apoptosis, and reduced insulin secretion, whereas knockdown reversed these effects. miR-506-5p could directly target PAK1 and negatively regulate its expression, and knockdown of PAK1 could reverse the protective effect of miR-506-5p inhibitor. CONCLUSIONS: miR-506-5p is highly expressed in T2DM, regulates pancreatic β-cell function by targeting and inhibiting PAK1, and participatesin the pathogenesis of T2DM.
INTRODUCTION: This prospective cohort study systematically compared neuropsychological impairments in Cushing's disease (CD),non-functioning pituitary adenomas (NFPA), and healthy controls (HCs), and investigated the rol...INTRODUCTION: This prospective cohort study systematically compared neuropsychological impairments in Cushing's disease (CD),non-functioning pituitary adenomas (NFPA), and healthy controls (HCs), and investigated the roles of HPA axis hormones (ACTH, cortisol)and inflammatory markers in cognitive dysfunction. MATERIAL AND METHODS: A total of 107 CD patients, 110 NFPA patients, and 84 HCs were enrolled from the Chinese PLA General Hospital.Participants underwent preoperative comprehensive neuropsychological assessments, including the Mini-Mental State Examination(MMSE) and Montreal Cognitive Assessment (MoCA), Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale (SDS), PittsburghSleep Quality Index (PSQI), and Quality of Life (QOL) Scale. Clinical data were also collected. Longitudinal neuropsychological changeswere evaluated in 90 CD patients post-surgery. Statistical analyses included FDR-corrected group comparisons, correlation analyses,and multivariable regression. RESULTS: Cushing's disease patients exhibited significantly greater deficits in global cognition (MMSE/MoCA, q < 0.001), depression/anxiety (SDS/SAS, q < 0.006), and quality of life compared with NFPA and HCs. Critically, morning ACTH levels (8 A.M.) predicted cognitive decline, whereas cortisol showed no significant correlation. Paradoxically, inflammatory markers (WBC, neutrophils, lymphocytes) positively correlated with MMSE scores (q < 0.024), suggesting compensatory neuroprotection, which needs further investigation. Postoperatively, significant improvements occurred in affective symptoms and cognition, with maximal recovery in memory and attention. CONCLUSIONS: The CD-specific neuropsychological impairments exceed tumor mass effects in NFPA, driven by HPA hyperactivation. ElevatedACTH is an associated predictor of cognitive decline, advocating for its prioritization in clinical monitoring. Surgical remission partiallyreverses deficits, while neuroendocrine-immune crosstalk bidirectionally modulates cognition. Adrenocorticotropic hormone-centricmanagement and targeted rehabilitation may optimize long-term outcomes.
Chronic stress and sustained activation of the hypothalamic-pituitary-adrenal (HPA) axis result in elevated cortisol secretion, which caninterfere with regulation of the hypothalamic-pituitary-thyroid (HPT) axis and affe...Chronic stress and sustained activation of the hypothalamic-pituitary-adrenal (HPA) axis result in elevated cortisol secretion, which caninterfere with regulation of the hypothalamic-pituitary-thyroid (HPT) axis and affect thyroid hormone metabolism and immune-mediatedmechanisms. The aim of this review is to present current evidence on the influence of stress and cortisol on thyroid function, including their effects onthe HPT axis, peripheral thyroid hormone metabolism, and autoimmunity, and to discuss potential clinical implications. A comprehensive literature search was conducted covering the last decade's clinical, population-based, and experimental studies addressingthe associations between psychological stress, cortisol levels, thyroid axis dysregulation, deiodinase activity, and autoimmune thyroiddisease. Mechanistic pathways and therapeutic perspectives are summarized. Evidence indicates that cortisol suppresses TRH and TSH secretion and disrupts the circadian rhythm of TSH secretion, while also influencingthyroid hormone transport proteins and deiodinase activity (↓ D1/↓ D2, ↑ D3), leading to reduced T3 and increased rT3. Thesemechanisms contribute to subclinical hypothyroidism and the non-thyroidal illness syndrome (NTIS) phenotype. Chronic stress alsodisturbs immune homeostasis (Treg/Th17 imbalance, elevated IL-6, TNF-α), increasing susceptibility to autoimmune thyroid diseases suchas Hashimoto's thyroiditis and Graves' disease. Emerging data suggest that stress-reduction interventions, optimization of micronutrientstatus (selenium, vitamin D, zinc), and modulation of the HPA axis may complement standard thyroid therapy. Stress and cortisol are significant but often underrecognized moderators of thyroid regulation through endocrine, metabolic, and immunologicalpathways. Incorporating assessment of chronic stress and HPA-axis activity into the diagnostic workup of thyroid disordersmay enhance clinical evaluation, and stress-targeted adjunctive interventions may improve management, particularly in patients withautoimmune thyroid disease.
Słomian S, Młynarek-Śnieżek K, Potyka A
… +3 more, Polok K, Kajdaniuk D, Marek B
Endokrynol Pol
· 2026 Jun · PMID 42370604
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INTRODUCTION: Renal cell carcinoma (RCC) is a common neoplasm with well-characterized risk factors, including obesity. The relationshipbetween adipocytokines and neoplasms remains an area of ongoing research. This study...INTRODUCTION: Renal cell carcinoma (RCC) is a common neoplasm with well-characterized risk factors, including obesity. The relationshipbetween adipocytokines and neoplasms remains an area of ongoing research. This study aimed to evaluate the activity of the adipocytokinenetwork in patients with RCC. MATERIAL AND METHODS: The study group comprised 28 patients with newly diagnosed RCC and 20 controls. Serum levels of adipocytokines (adiponectin, irisin, omentin, visfatin, chemerin, resistin, apelin, vaspin, and nesfatin-1) were measured using enzyme-linkedimmunosorbent assay (ELISA). All subjects had a BMI < 30 kg/m2 and normal renal function and did not have any of the diseases listedin the exclusion criteria. RESULTS: Patients in the RCC group had lower serum levels of irisin (3.78 vs. 5.34 μg/mL, p < 0.001), adiponectin (4.92 vs. 6.89 μg/mL, p = 0.013), and nesfatin-1 (1291.0 vs. 1884.3 pg/mL, p = 0.019) than those in the control group. Resistin levels were higher in the RCC group (7.64 vs. 6.38 ng/mL, p = 0.044). We found no significant differences in the concentrations of chemerin, visfatin, apelin, vaspin, and omentin.We observed differences in correlations among adipocytokines across the study groups. In patients with RCC, positive correlations wereobserved between resistin and chemerin, resistin and vaspin, resistin and omentin, and vaspin and omentin; negative correlationswere observed between chemerin and adiponectin, resistin and irisin, and vaspin and irisin. In controls, positive correlations were observedbetween visfatin and resistin, visfatin and vaspin, chemerin and nesfatin-1, resistin and vaspin, and nesfatin-1 and apelin. CONCLUSIONS: The adipocytokine profile in patients with RCC differs from that of controls. This suggests their potential role as prognostic, diagnostic, and monitoring tools in RCC. It also suggests that patients with RCC have distinct metabolic profiles.
Soltanova L, Sahin S, Durcan E
… +6 more, Yılmaz E, Uysal S, Muradov I, Kocaman BB, Gonen MS, Onur I
Endokrynol Pol
· 2026 Jun · PMID 42370603
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INTRODUCTION: Rapid on-site evaluation (ROSE) is thought to increase the adequacy of thyroid fine-needle aspiration (FNA) biopsiesand reduce overall cost. MATERIAL AND METHODS: We conducted a retrospective review of thyr...INTRODUCTION: Rapid on-site evaluation (ROSE) is thought to increase the adequacy of thyroid fine-needle aspiration (FNA) biopsiesand reduce overall cost. MATERIAL AND METHODS: We conducted a retrospective review of thyroid FNA cases from patients who presented to the endocrinology outpatient clinic of a tertiary center between May 2018 and March 2023. A cytopathologist performing ROSE in an FNA room in the endocrinologyclinic was available during the period June 2019-March 2023. Between May 2018 and June 2019, ROSE was not available. RESULTS: Of 1614 FNAs, 1212 were performed with ROSE by a cytopathologist and 402 without ROSE. The number of nondiagnostic FNA cases was 297 (24.6%) with ROSE and 140 (34.8%) without ROSE. In Group A (with ROSE), a total of 94 of 1212 nodules underwent repeatbiopsy, corresponding to a rate of 7.75%. In Group B (without ROSE), 59 of 402 nodules required repeat biopsy, yielding a rate of 14.7%. CONCLUSIONS: Although cytopathologist assistance during thyroid FNA increases costs, it lowers insufficiency rates by reducing the need for repeat procedures and expedites the time to definitive diagnosis.
Endokrynol Pol
· 2026 Jun · PMID 42345331
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INTRODUCTION: This study used optical coherence tomography angiography (OCTA) to investigate the early diagnostic value of OCTAparameters for diabetic kidney disease (DKD) in patients with non-proliferative diabetic reti...INTRODUCTION: This study used optical coherence tomography angiography (OCTA) to investigate the early diagnostic value of OCTAparameters for diabetic kidney disease (DKD) in patients with non-proliferative diabetic retinopathy (NPDR). MATERIAL AND METHODS: This prospective study enrolled patients with type 2 diabetes mellitus (T2DM) into three groups: those with T2DMwithout retinopathy (group A), those with non-proliferative diabetic retinopathy (NPDR) without DKD (group B), and those with NPDR andDKD (group C). All participants underwent OCTA imaging to measure vessel density (VD) in the superficial capillary plexus (SCP)and deep capillary plexus (DCP), as well as the foveal avascular zone (FAZ) area, perimeter (PERIM), and acircularity index (AI). Pearsonor Spearman correlation analysis was used to explore the relationships between OCTA parameters and renal function indicators, including24-hour urinary microalbumin, urinary albumin-to-creatinine ratio (UACR), and blood urea nitrogen (BUN). Multivariate logistic regressionwas performed to identify independent factors associated with NPDR with DKD. Receiver operating characteristic (ROC) curveswere generated to assess the diagnostic performance of individual and combined OCTA parameters. RESULTS: Significant differences in OCTA parameters and renal function indicators were observed among the three groups. Correlation analysis revealed that SCP-VD and DCP-VD were negatively correlated with 24-hour urinary microalbumin, UACR, and BUN, whereas FAZ area, PERIM, and AI were positively correlated with these renal markers. Multivariate logistic regression identified SCP-VD [oddsratio (OR) = 0.67], DCP-VD (OR = 0.68), PERIM (OR = 1.30), and AI (OR = 1.04) as independent factors associated with NPDR and DKD.Analysis of diagnostic performance showed that among the single parameters, SCP-VD had the best diagnostic value [area under the curve(AUC) = 0.80]. Among the different combination models, the combination of all four parameters demonstrated the highest diagnosticperformance (AUC = 0.94). CONCLUSIONS: OCTA parameters (SCP-VD, DCP-VD, PERIM, AI) are closely associated with NPDR and DKD. A combined multiparametermodel demonstrated excellent diagnostic efficacy for early detection. Retinal OCTA parameters may reflect early microvascular alterationsassociated with diabetic kidney disease.
INTRODUCTION: Papillary thyroid carcinoma (PTC) has a high incidence, and identifying key molecules is crucial for improving its treatment.This study aimed to clarify the expression, prognostic value, biological function...INTRODUCTION: Papillary thyroid carcinoma (PTC) has a high incidence, and identifying key molecules is crucial for improving its treatment.This study aimed to clarify the expression, prognostic value, biological function, and regulatory mechanism of CSDE1 in PTC. MATERIAL AND METHODS: Bioinformatics analysis of TCGA data, RT-qPCR, and western blot assays were used to detect CSDE1/METTL3expression in PTC tissues and cells. CCK-8, colony formation, wound-healing, and Transwell assays were used to evaluate cell phenotypes.MeRIP-qPCR was used to detect m⁶A modification. A dual-luciferase reporter assay was used to confirm regulatory relationships. Pearsoncorrelation analysis was used to evaluate clinical correlations. RESULTS: CSDE1 was highly expressed in PTC and correlated with advanced clinical features and poor prognosis. CSDE1 knockdownsuppressed the proliferation, migration, invasion, and EMT of PTC cells. CSDE1 activated the Wnt/β-catenin pathway. Moreover, METTL3negatively regulated CSDE1 expression via m⁶A modification. CONCLUSIONS: CSDE1 promotes PTC progression through the Wnt/β-catenin pathway under the regulation of METTL3-mediated m⁶A modification, serving as a promising prognostic biomarker and therapeutic target.
INTRODUCTION: Posterior pituitary tumors (PPTs) are rare pathologies universally identified by positive immunoreactivity for thyroidtranscription factor-1 (TTF-1). They include four subtypes: pituicytoma (PC), granular c...INTRODUCTION: Posterior pituitary tumors (PPTs) are rare pathologies universally identified by positive immunoreactivity for thyroidtranscription factor-1 (TTF-1). They include four subtypes: pituicytoma (PC), granular cell tumor (GCT), spindle cell oncocytoma (SCO),and sellar ependymoma (SE). Because these tumors are rare, data regarding the optimal treatment strategy and prognosis are lacking. The aim of our study was to describe a large single-center cohort of patients with PPTs. MATERIAL AND METHODS: We retrospectively analyzed data from 15 patients diagnosed with PPTs among 2108 patients who underwent pituitary surgery at our institution between 2009 and 2024, examining their clinical presentations, imaging studies, surgical techniques, and recovery trajectories. The mean age was 50.5 years (range, 18-74 years). The mean follow-up time was 6.4 years (range, 0-15 years). RESULTS: We describe eight cases of PC, four of SCO, and three of GCT. The most common symptoms were visual impairment (46.7%) and headache (40.0%). Thirteen patients (86.7%) underwent endoscopic transsphenoidal surgery, ten of whom achieved gross total resection (GTR). CONCLUSIONS: The endoscopic transsphenoidal approach has proven to be a safe and highly effective method for achieving GTR in patients with PPTs. Spindle cell oncocytoma, with a higher level of vascularization than PC and GCT, poses a greater risk of surgical complicationsand may result in non-GTR.
INTRODUCTION: The aim of the study was to present the role of socioeconomic factors in fracture risk among postmenopausal women. MATERIAL AND METHODS: The study group consisted of 508 consecutive postmenopausal women rec...INTRODUCTION: The aim of the study was to present the role of socioeconomic factors in fracture risk among postmenopausal women. MATERIAL AND METHODS: The study group consisted of 508 consecutive postmenopausal women recruited from three osteoporotic outpatient clinics. The mean age was 69.8 ± 7.5 years. Data on clinical factors, as well as urban/rural residence, education, occupation, and maritalstatus, were collected. Bone status was assessed at the hip using a Lunar Prodigy device. Fracture risk over the next 10 years, expressedas a percentage, was established using the FRAX (major fractures), Garvan (any fractures), and POL-RISK (any fractures) algorithms. RESULTS: The mean risk was 8.95 ± 6.43% for FRAX and 29.71 ± 20.53% and 28.1 ± 14.85% for Garvan and POL-RISK, respectively. Fracture risk calculated by any of the analyzed calculators was not influenced by place of residence or level of education. The type of job was relatedto fracture risk according to the FRAX major calculator only; the risk was significantly higher in the unemployed group compared with thethree remaining subgroups - those performing sedentary work, physical work, or standing work. The type of work had no effect onthe risk according to the other calculators. Although marital status, particularly widowhood, was associated with higher fracture risk inunivariate analysis, this effect was not significant after adjustment for age, suggesting that age is the underlying factor. CONCLUSIONS: Socioeconomic factors were associated with fracture risk, and data on socioeconomic status should be incorporated into patient assessment for osteoporosis.
INTRODUCTION: Post-COVID-19 condition (PCC) is often accompanied by endocrine and immune dysregulation. Growth hormone (GH)deficiency has been reported in PCC patients, but its systemic effects remain poorly defined. MAT...INTRODUCTION: Post-COVID-19 condition (PCC) is often accompanied by endocrine and immune dysregulation. Growth hormone (GH)deficiency has been reported in PCC patients, but its systemic effects remain poorly defined. MATERIAL AND METHODS: Eighty-eight PCC patients were classified into four groups based on GH levels (A: GH ≥ 10 ng/mL; B:5 ng/mL ≤ GH < 10 ng/mL; C: 1 ng/mL ≤ GH < 5 ng/mL; D: GH < 1 ng/mL), and insulin tolerance testing was performed to assess GH and cortisol levels. Serum samples from PCC patients were analyzed using proteomics and metabolomics, followed by correlation analyseswith GH and cortisol levels. RESULTS: There were significant differences among the four groups in GH levels at baseline, 30, 60, 90, and 120 minutes after ITT. Similarly, cortisol levels at 30, 60, 90, and 120 minutes post ITT also showed significant differences among the four groups. Proteomic profiling identifiedsignificant alterations of proteins in complement and coagulation cascades across different GH levels. Compared with group B, groupD (GH deficiency) showed reduced expression of lipid transport proteins (such as APOB, APOH, and APOF), consistent with the lowerserum low-density lipoprotein cholesterol (LDL-C) levels observed in the GH deficiency group. Integrative analysis of comparisons amonggroups highlighted SPARCL1 as a hub protein linked to GH dysregulation, showing a critical response to declining GH. Correlation analysisalso revealed strong associations of F/GH levels with complement-related proteins and SPARCL1. Metabolomic profiling revealed that L-glutamic acid and traumatic acid were significantly elevated in group C compared with group B, with AUC values of 0.657 and 0.739,respectively, indicating that these metabolites can distinguish patients with normal GH from those with GH deficiency. In addition, tetradecanedioicacid, which was markedly increased in group C compared to group D, showed a significant positive correlation with GHlevels at multiple time points. Integrated proteomic and metabolomic analyses further demonstrated significant associations betweendifferentially abundant proteins and metabolites. CONCLUSIONS: Our integrated proteomic-metabolomic analysis reveals that GH deficiency in PCC patients is associated with complement dysregulation, highlighting SPARCL1 as a potential biomarker of GH deficiency in PCC patients.
INTRODUCTION: Differentiated thyroid cancer (DTC), including papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC), isthe most common endocrine malignancy and is usually associated with a favorable pro...INTRODUCTION: Differentiated thyroid cancer (DTC), including papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC), isthe most common endocrine malignancy and is usually associated with a favorable prognosis. However, clinicopathological characteristicsand prognostic factors may differ between these histological subtypes. MATERIAL AND METHODS: We performed a retrospective analysis of 1,826 consecutive patients (1,533 with PTC and 293 with FTC) whounderwent surgical treatment between 1995 and 2025 at a tertiary referral center. Clinicopathological features, recurrence patterns,and disease-specific survival (DSS) were assessed. Tumors were staged according to the AJCC/UICC TNM classification (8th edition).Survival probabilities were estimated using the Kaplan-Meier method and compared with the log-rank test. Independent prognosticfactors were evaluated using multivariable Cox proportional hazards regression analysis. RESULTS: Follicular thyroid carcinoma was significantly associated with larger tumor size, extrathyroidal extension, and distant metastases at diagnosis, whereas lymph node metastases and multifocality were more frequently observed in PTC. Ten-year DSS was significantly higherin patients with PTC than in those with FTC (98.4% vs. 89.6%; p < 0.001). In multivariable analysis, older age, larger tumor size, and distantmetastases were independent predictors of worse DSS in PTC. In FTC, extrathyroidal extension, locoregional recurrence, and distant metastaseswere independently associated with reduced DSS. CONCLUSIONS: Although long-term survival in DTC is excellent, significant differences in biological behavior and prognostic determinantsexist between PTC and FTC. Histology-specific risk assessment may improve long-term management and follow-up strategies.
Arczewska KD, Kucharczyk M, Grzanka M
… +9 more, Życka-Krzesińska J, Białas A, Rybicka B, Kossowska H, Koblowska M, Bogusławska J, Nilsen H, Piekiełko-Witkowska A, Gellert R
INTRODUCTION: Flozins, an emerging class of antidiabetic agents, selectively target the SGLT2 sodium/glucose cotransporter in the renalproximal tubule, thereby preventing glucose reabsorption and reducing hyperglycemia....INTRODUCTION: Flozins, an emerging class of antidiabetic agents, selectively target the SGLT2 sodium/glucose cotransporter in the renalproximal tubule, thereby preventing glucose reabsorption and reducing hyperglycemia. Beyond lowering glucose levels, flozins exhibitsignificant benefits in heart failure and chronic kidney disease. This expanded therapeutic utility is noteworthy, particularly given the absenceof SGLT2 expression in cardiac tissue, suggesting the involvement of additional targets or mechanisms affected by flozins. MATERIAL AND METHODS: Here, we utilized Caenorhabditis elegans as a model organism devoid of an SGLT2 orthologue to analyze the off-targetactivity of flozins, specifically following dapagliflozin treatment. Glucose-fed worms were treated with dapagliflozin, and lifespan analyseswere performed. Transcriptomic profiling was conducted to compare glucose- and dapagliflozin-treated worms with glucose-only-treatedcontrols. In vivo glucose transport was assessed using the fluorescent glucose analogue 2-NBDG. Additionally, smvt-1 (sodium-dependentmultivitamin transporter) expression was downregulated to evaluate its role in dapagliflozin-mediated effects. RESULTS: Although C. elegans lacks an SGLT2 orthologue, dapagliflozin remarkably mirrored observations from murine models by significantlyprolonging lifespan under glucose-fed conditions. Transcriptomic analyses revealed gene expression profiles closely resemblingthose observed in mammalian systems. Furthermore, we observed that dapagliflozin inhibits glucose transport in vivo, as demonstratedby reduced 2-NBDG uptake. Notably, this inhibitory effect was abolished upon downregulation of smvt-1, indicating its involvement indapagliflozin-mediated glucose transport inhibition. CONCLUSIONS: Our findings suggest that dapagliflozin exerts SGLT2-independent effects on glucose transport and longevity. In C. elegans, the sodium-dependent multivitamin transporter SMVT-1 represents a relevant target of dapagliflozin, providing insight into potentialalternative mechanisms underlying the pleiotropic benefits of flozins observed in mammals.
INTRODUCTION: Obesity is characterized by hypothalamic dysfunction and metabolic dysregulation. While high-intensity interval training (HIIT) effectively treats obesity, the underlying central mechanisms remain unclear....INTRODUCTION: Obesity is characterized by hypothalamic dysfunction and metabolic dysregulation. While high-intensity interval training (HIIT) effectively treats obesity, the underlying central mechanisms remain unclear. This study aims to investigate HIIT's effects onmetabolic parameters and hypothalamic gene expression, exploring possible pathways linking central and peripheral adaptations. MATERIAL AND METHODS: Our study evaluated HIIT-induced metabolic changes in male diet-induced obese (DIO) mice. Body weightand caloric intake were recorded throughout the intervention period, and glucose regulation was assessed via glucose tolerance test(GTT) and insulin tolerance test (ITT). Following the HIIT intervention, blood was collected for cytokine assessment and hypothalamictissue was harvested for molecular characterization. RNA sequencing (RNA-seq) was employed to analyze gene expression, with enrichmentanalysis to identify biological pathways, and reverse transcription quantitative polymerase chain reaction (RT-qPCR) to validate keyfindings. Protein expression was examined through Western blotting, and circulating cytokine levels were quantified using enzyme-linkedimmunosorbent assay (ELISA). RESULTS: High-intensity interval training significantly reduced caloric intake while improving glucose metabolism and insulin sensitivity in DIO mice, accompanied by hypothalamic transcriptomic remodeling. RNA-seq identified 178 upregulated and 292 downregulated genes post-HIIT,with pathway enrichment analysis revealing activation of interleukin 17 (IL-17) signaling. Notably, HIIT increased hypothalamic lipocalin 2(Lcn2) mRNA and protein expression, which correlated with decreased hypothalamic apoptosis and elevated hypothalamic pro-opiomelanocortin(POMC) expression in DIO mice. Consistently, circulating IL-17 levels were elevated following HIIT intervention. CONCLUSIONS: Collectively, our findings identify hypothalamic Lcn2 as a prominent molecular responder to short-term HIIT training, whoseupregulation parallels enhanced IL-17 signaling and coincides with the recovery of POMC neurons.
INTRODUCTION: Colon cancer (CC) remains a major global health burden and ranks among the most common malignant tumors. In recentyears, its growing occurrence in younger age groups has presented a substantial challenge to...INTRODUCTION: Colon cancer (CC) remains a major global health burden and ranks among the most common malignant tumors. In recentyears, its growing occurrence in younger age groups has presented a substantial challenge to public health systems worldwide. Type 2diabetes (T2D) and gut microbiota may influence its pathogenesis, but the causal relationship remains unexplored. This study aims to examine the causal association between T2D and CC and explore the possible mediating effects of gut microbiota inthis relationship. MATERIAL AND METHODS: A two-sample Mendelian randomization (MR) design was employed to assess causality, with T2D and gut microbiotaas exposures and CC as the outcome variable. Mediation analysis was conducted through the two-step Mendelian randomizationmethod. Additionally, scRNA-seq data were analyzed to characterize the expression patterns of T2D drug target genes in CC. RESULTS: The study revealed a markedly positive causal effect of T2D on benign colon neoplasm risk (odds ratio = 1.074, 95% confidenceinterval: 1.031-1.119, p = 6.084e-4). Further analysis detected 24 gut microbial taxa related to CC risk, among which Bacteroides sp003545565partially mediated the T2D-benign colon neoplasm relationship, accounting for 8.57% of the total effect. scRNA-seq analysis demonstrateddistinct expression profiles of T2D drug target genes (e.g., PPARG, DPP4, INSR, GPD2, and PRKAB1) in CC compared to normal tissues,with cell type-specific expression changes linked to CC progression. CONCLUSIONS: This study provided genetic evidence confirming a causal role of T2D in CC and highlighted the potential mechanisticinvolvement of gut microbiota. These findings suggested novel intervention strategies for CC prevention and treatment.
INTRODUCTION: Severe growth hormone deficiency (GHD) in adults is associated with unfavorable metabolic disturbances and adversechanges in body composition, contributing to increased cardiovascular risk and impaired qual...INTRODUCTION: Severe growth hormone deficiency (GHD) in adults is associated with unfavorable metabolic disturbances and adversechanges in body composition, contributing to increased cardiovascular risk and impaired quality of life. Although recombinant humangrowth hormone (rhGH) replacement therapy is an established treatment, data reflecting its effects under real-world clinical conditionsin Poland remain limited. MATERIAL AND METHODS: This retrospective, real-world study included adult patients with severe GHD treated with rhGH within the nationaldrug program at a single tertiary endocrine center. Serum insulin-like growth factor 1 (IGF-1), lipid profile, glycemic parameters,and body composition assessed by bioelectrical impedance analysis were evaluated at baseline, after 6 and 12 months of therapy, and atthe last follow-up. RESULTS: Recombinant human GH therapy was associated with a sustained increase in serum IGF-1 concentrations throughout the observationperiod. Treatment was accompanied by a reduction in total cholesterol and low-density lipoprotein cholesterol levels, while norelevant changes were observed in high-density lipoprotein cholesterol, triglycerides, or glycated hemoglobin. After 12 months of therapy,a decrease in total fat mass and body fat percentage was observed, along with an increase in relative muscle mass. Favorable regionalchanges in body composition involved the trunk as well as upper and lower limbs. No meaningful changes were detected in absolutemuscle mass, bone mass, or total body water. CONCLUSIONS: In adults with severe GHD, rhGH replacement therapy administered under routine clinical practice conditions is associated with beneficial changes in lipid profile and favorable body recomposition, characterized by reduced adiposity and increased relative muscle mass. These findings support the effectiveness of long-term, individualized rhGH therapy in adult patients with GHD.