Background: Management of giant pyogenic liver abscesses (PLA) remains challenging, particularly in culture-negative cases, where clinical improvement may not reflect adequate local disease control. Case Description: A 65-year-old woman with well-controlled type 2 diabetes mellitus presented with several weeks of systemic symptoms, marked inflammatory response, cholestatic liver injury, and acute kidney dysfunction. Contrast-enhanced computed tomography (CT) and magnetic resonance imaging (MRI) revealed a large, multiloculated hepatic lesion measuring approximately 10 cm, consistent with a giant PLA. Empirical broad-spectrum antimicrobial therapy resulted in rapid clinical and biochemical improvement; however, follow-up imaging demonstrated further enlargement of the abscess. Microbiological cultures from blood, urine, and the abscess cavity remained negative. In view of radiological progression, CT-guided percutaneous catheter drainage was performed, resulting in effective evacuation and subsequent lesion regression. Long-term follow-up confirmed complete resolution without recurrence. Conclusions: This case highlights that clinical and laboratory improvement alone may be insufficient to assess treatment response in giant, culture-negative PLA. Serial imaging plays a key role in identifying inadequate local disease control and guiding timely escalation to image-guided intervention.

Diabetic peripheral neuropathy is an important cause of functional disability, and current therapies have limited ability to halt its progression. Uridine, a pyrimidine nucleoside essential for the synthesis of membrane phospholipids and neuronal metabolism, appears to be a potential neuroprotective agent, but its impact on motor behavior and peripheral nerve integrity in diabetes remains insufficiently investigated. Our study investigated the effects of chronic uridine supplementation on locomotor performance, neuromuscular electrophysiological manifestations, and morphological changes in the sciatic nerve in a murine model of streptozotocin-induced diabetes. We used male C57BL/6 mice (n = 8/group) that were assigned to three groups: sham (no diabetes), diabetic (streptozotocin-induced, diabetes mellitus, DM+), and diabetic treated with uridine (DM+U). We observed that uridine did not alter the metabolic status, as the HbA1c values remained comparable between diabetic groups (9.93 ± 0.57% DM+ vs. 9.71 ± 0.55% DM+U; p = 0.72), suggesting effects independent of glycemic control. The open field test revealed that diabetic mice showed a marked reduction in spontaneous locomotion, while uridine-treated mice maintained a significantly higher level of activity (longer total distance traveled 3761.7 ± 789.1 cm vs. 2477.5 ± 1017.6 cm in DM+; p = 0.023). Electrophysiological evaluation revealed near-normal sciatic nerve function in DM+U mice, including higher compound motor action potential (CMAP) amplitudes (10.21 ± 0.64 mV vs. 5.75 ± 0.72 mV; p < 0.0001) and reduced F-wave latency (6.35 ± 0.45 ms vs. 7.29 ± 0.31 ms; p < 0.0001). Histological and immunohistochemical analyses (PGP 9.5) further confirmed reduced nerve degeneration in DM+U mice. Our data suggest that chronic uridine administration may confer both functional and structural neuroprotection in diabetic neuropathy, even in the absence of improved glycemic control.

Diabetes mellitus (DM) is a group of metabolic diseases characterized by chronic hyperglycemia resulting from defects in insulin secretion, insulin action, or both. The most common types-type 1 and type 2 diabetes-have different etiologies and pathophysiological mechanisms. Type 1 diabetes (T1DM) results from autoimmune destruction of the insulin-producing pancreatic β-cells, leading to the development of absolute insulin deficiency, whereas in type 2 diabetes (T2DM), impaired carbohydrate metabolism is primarily caused by insulin resistance and relative insulin deficiency. Current diagnostic criteria do not allow for the detection of the disease at the preclinical stage. MicroRNA (miRNA) influences post-translational regulation of gene expression by inhibiting mRNA translation and also promotes mRNA degradation. The aim of this review is to summarize current evidence on the role of microRNAs in the pathogenesis of T1DM and T2DM and to evaluate their potential as early diagnostic biomarkers and therapeutic targets. It is demonstrated that T1DM and T2DM exhibit altered expression of specific microRNAs involved in β-cell apoptosis, autoimmune inflammation, and insulin signaling. In T1DM, key miRNAs include miR-21, miR-25, miR-146a, and miR-375, which reflect β-cell destruction and the autoimmune process. In T2DM, critical roles are played by miR-9, miR-29, miR-34a, miR-103/107, miR-126, miR-143, and miR-375, which regulate insulin secretion, lipid metabolism, and tissue insulin sensitivity. Particular attention is given to microRNAs whose expression changes several years before clinical disease onset (miR-15a, miR-126, miR-375), offering opportunities for early diagnosis. Data are presented on circulating miRNAs in stable biological fluids (blood, urine). It should be emphasized, however, that the proposed microRNA panel currently represents only a potential diagnostic tool. This panel requires further validation and confirmation by clinicians in large-scale prospective studies and does not yet claim to be ready for routine clinical use. Nevertheless, the development of such a universal microRNA panel, followed by thorough clinical evaluation, has promising biomedical potential, which will not only allow for the diagnosis of diabetes at an early stage but also identify new therapeutic targets for personalized medicine.

Diabetes mellitus is a chronic and progressive metabolic disorder associated with abnormal blood glucose levels. The term involves several diseases with different pathophysiology mechanisms and treatment strategies. Stem cell-based treatments represent an emerging strategy for patients with diabetes mellitus with severe pancreatic insufficiency and poor glycemic control. Over the last 20 years, researchers have investigated mesenchymal stem cell infusion and the transplantation of stem cell-derived β cells and islet tissues. This review aims to comprehensively discuss the latest advances in the field of stem cell use in diabetes, including clinical studies and preclinical experiments aiming at improving the efficacy and safety of stem cell use.

Of the many clinical phenotypes of obesity, the most prevalent are metabolically "healthy" (MHO) and metabolically "unhealthy" (MUO) obesities, the latter being associated with a range of comorbidities, including type 2 diabetes mellitus (T2DM). The underlying causes of different obesity phenotypes and the mechanisms of conversion of one phenotype into another have yet to be fully elucidated. However, increasing evidence suggests the key role of low-grade metabolic inflammation (metaflammation) in the pathogenesis of obesity and metabolic dysfunction. The review presents a comprehensive description of changes in immune cell populations and pro-inflammatory mediators, as well as a detailed comparative mapping of the adipose tissue immune landscape during MHO/MUO transition. Based upon a conceptual model for the intensification of metaflammation during MHO progression and conversion to MUO, a pattern of dynamical changes that accompany MHO/MUO transition is described. Though many parameters demonstrate significant differences in multiple cross-sectional and some longitudinal studies, only a few of them (CRP, IL-6, IL-17A, absolute counts of leukocytes and neutrophils) meet the criteria of a validated biomarker in clinical setting. A lack of standardization in MHO definition and heterogeneity in the severity of MUO make the search for predictive biomarkers a challenge. The review also discusses the mechanisms underlying metabolic memory and the incomplete reversibility of metabolic disturbances after bariatric surgery.

Aims: The aim of this study was to investigate the associations between symptomatic hearing loss (HL), neuropathy, and nephropathy in subjects with Type 2 diabetes mellitus (T2DM). Furthermore, the study evaluated whether HL was associated with chronic low-grade inflammation, assessed based on plasma levels of tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and high-sensitivity C-reactive protein (hsCRP), and explored potential sex-specific differences. Materials and Methods: We included 4245 subjects with T2DM from The Danish Centre for Strategic Research in Type 2 Diabetes cohort. Symptomatic HL was defined using ICD-10 codes. In 2016, a questionnaire was sent out to evaluate neuropathy using the Michigan Neuropathy Screening Instrument (MNSI ≥ 4). Nephropathy was defined as urinary albumin-to-creatinine ratio (UACR) >30 mg/g. Plasma levels of TNF-α, IL-6, and hsCRP were measured at enrolment from 2010 to 2016. Multivariable logistic regression was used, adjusting for covariates. Results: Neuropathy was significantly associated with HL (OR = 1.83, 95%CI [1.42, 2.35], p < 0.001), and the association was stronger in women (OR = 2.74 [1.81, 4.14], p < 0.001) compared to men (OR = 1.44 [1.04, 1.99], p < 0.05) (P-interaction = 0.020). No significant association was found between nephropathy and HL. Among inflammatory markers, only the highest tertile of TNF-α levels was significantly associated with HL compared to the lowest tertile (OR = 1.40 [1.07, 1.82], p < 0.05) without any sex interaction. Conclusions: In subjects with T2DM, neuropathy was associated with symptomatic HL, and the association seemed to be stronger in females. Among chronic low-grade inflammation markers, only TNF-α was significantly associated with symptomatic HL. Additionally, no significant association was found between nephropathy and HL.

Metabolic dysfunction-associated steatotic liver disease (MASLD) has replaced older exclusion-based terminology as the preferred term for steatotic liver disease associated with cardiometabolic risk factors. MASLD is now among the most common causes of chronic liver disease and may progress from simple steatosis to metabolic dysfunction-associated steatohepatitis (MASH), fibrosis, cirrhosis, and hepatocellular carcinoma. This updated rigorous narrative review synthesizes current evidence on MASLD diagnosis and management, with emphasis on the gut-liver axis and the therapeutic potential of combining probiotics with metformin. A structured narrative search was conducted in PubMed, PMC, ScienceDirect, Taylor & Francis, Cochrane Library, and Google Scholar using the keywords "MASLD", "MAFLD", "NAFLD", "MASH", "probiotics", "synbiotics", "metformin", and "gut-liver axis". The review was designed as a narrative synthesis rather than a systematic review. Current guidance supports stepwise risk stratification using serum fibrosis scores followed by elastography or advanced imaging when indicated. Ultrasonography remains accessible but has limited sensitivity for mild steatosis, is operator-dependent, and is not sufficient for comprehensive assessment of fibrosis or disease activity. Metformin is appropriate for type 2 diabetes mellitus and improves insulin resistance, but current guidelines do not recommend it as a targeted treatment for MASH because histological benefit has not been consistently demonstrated. Probiotics and synbiotics may improve aminotransferases, inflammatory markers, lipid parameters, intestinal barrier function, and gut dysbiosis; however, findings vary by strain, formulation, dose, treatment duration, population, and endpoint. The combination of probiotics and metformin is mechanistically plausible because it targets both metabolic dysfunction and intestinal dysbiosis, but human evidence remains limited. Larger, strain-specific, adequately powered trials using standardized MASLD criteria and clinically meaningful endpoints are required before routine clinical recommendations.

Introduction: Cardiovascular diseases (CVDs) are a vast and widespread problem around the world, responsible for around one third of global deaths, of which 85% were due to heart attack and stroke in 2022. There are a lot of well-established risk factors for CVDs, including smoking, diabetes mellitus, obesity, poor diet, alcohol use, and sedentary lifestyle. Psychiatric disorders, however, are not among those frequently cited. Over a billion people worldwide suffer from some kind of mental disorder, with anxiety and depression being among the leading causes of long-term disability. All-cause death is significantly elevated in individuals with all mental health disorders. Methods: This narrative review aims to provide details on the selected psychiatric disorders and their pharmacotherapy with regard to the risk of developing cardiac illness by reviewing the available literature and the 2025 ESC Clinical Consensus Statement on mental health and cardiovascular disease. Results: Primary and secondary prevention of cardiovascular complications in the psychiatric disease population is an essential component in clinical healthcare. Conclusions: Taking all into account, it is essential to underline the role of the activation of the sympathetic nervous system and chronic inflammation, ultimately leading to metabolic syndrome in individuals with mental disorders, as well as an increase in residual cardiovascular risk and the development of CVDs, thereby worsening their long-term prognosis. In view of risky lifestyle behaviors in this population, it is essential to screen proactively, mitigate risk factors, consider the role of pharmacotherapy, and, if needed, initiate appropriate treatment.

Background and Aims: Automated insulin delivery (AID) systems are standard of care for type 1 diabetes mellitus (T1DM). Tubeless AID systems may improve treatment acceptance, but real-world European data in patients transitioning from multiple daily injections (MDI) or open-loop patch pump therapy are limited. This study evaluated real-world glycemic, safety, and quality-of-life (QoL) outcomes after transition to a tubeless automated closed-loop system (Omnipod 5^®, OP5^®). Research Design and Methods: In this prospective, multicenter observational study, adults with T1DM transitioned from MDI or open-loop continuous subcutaneous insulin infusion to OP5^® and were followed for 180 days. Continuous glucose monitoring-derived metrics and validated patient-reported outcome measures were assessed. Subgroup analyses were performed by prior therapy. Results: Of the 94 enrolled participants, 88 completed the study. At 180 days, HbA1c decreased from 7.5% to 7.1% (p < 0.001), and time in range increased from 59.0% to 68.0% (p < 0.001) without increased hypoglycemia. The proportion achieving TIR_70-180 ≥ 70% rose from 12.5% to 43.2%. Improvements were greater among prior MDI users. Treatment satisfaction and diabetes-related QoL improved significantly. The mean time in automated mode was 90.9%. Conclusions. Transition to tubeless AID significantly improved glycemic and psychosocial outcomes, supporting its effectiveness in routine clinical practice.

Background: Metabolic syndrome is characterized by dysregulated glucose metabolism and is a major risk factor for type 2 diabetes mellitus and cardiovascular disease. Although glucose-lowering therapies such as glucagon-like peptide-1 receptor (GLP-1R) agonists are effective, their use may be limited by cost, administration route, side effects and tolerability. Bergamot (Citrus bergamia Risso et Poiteau) extract, rich in flavanones, has shown favorable metabolic effects in clinical studies, although its mechanisms of action remain insufficiently defined. This study aimed to investigate the potential glucose-modulating mechanisms of a standardized phospholipid-formulated bergamot extract (BP) (Vazguard™) in vitro. Methods: GLP-1R activation was assessed in a U2OS cell line expressing cyclic adenosine monophosphate (cAMP)-sensitive Nomad Biosensors™. Dipeptidyl peptidase-4 (DPP4) activity was evaluated using a cell-free enzymatic assay, while Glucose transporter type 4 (GLUT4)-mediated glucose uptake was assessed in CHO-K1 cells stably expressing human GLUT4 using an adenosine triphosphate (ATP)-based readout. Cytotoxicity was also using lactate dehydrogenase (LDH), MTT, and nuclei count assays. Results: BP exhibited a dose-dependent (0.31-5 mg/mL) increase in cAMP biosensor fluorescence, consistent with GLP-1R-associated signaling and a maximal response of approximately 60% relative to the positive control (GLP-1R agonist II). No cytotoxic effects were observed. In contrast, BP showed no inhibitory effect on DPP4 activity and did not alter GLUT4-mediated glucose uptake under the experimental conditions tested. Conclusions: These findings provide novel mechanistic evidence that phospholipid-formulated bergamot extract suggests a possible involvement in GLP-1R-associated signaling in vitro, without detectable effects on DPP4 or GLUT4 pathways under the conditions tested. This suggests a mechanism consistent with weak agonist or allosteric modulation of GLP-1R and supports further investigation of bergamot formulated with phospholipids as potential natural adjuncts in metabolic health management.