Search Results (297)

Nephrotic syndrome (NS) is characterized by proteinuria, hypoalbuminemia, edema, and hyperlipidemia. Apart from the traditional causes of NS, such as minimal change disease, focal segmental glomerulosclerosis, diabetes, infections, malignancies, autoimmune conditions, and nephrotoxic agents, there are also rare causes of NS, whose knowledge is of the utmost importance. The aim of this article was to highlight the less well-known causes that have a significant impact on diagnosis and treatment. Genetic syndromes such as Schimke immuno-osseous dysplasia, familial lecithin-cholesterol acyltransferase deficiency with two clinical variants (fish-eye Disease and the p.Leu364Pro mutation), lead to NS through mechanisms involving podocyte and lipid metabolism dysfunction. Congenital disorders of glycosylation and Nail–Patella Syndrome emphasize the role of deranged protein processing and transcriptional regulation in glomerular injury. The link of NS with type 1 diabetes, though rare, suggests an etiology on the basis of common HLA loci and immune dysregulation. Histopathological analysis, particularly electron microscopy, shows mainly podocyte damage, mesangial sclerosis, and alteration of the basement membrane, which aids in differentiating rare forms. Prompt recognition of these novel etiologies by genetic analysis, renal biopsy, and an interdisciplinary panel is essential to avoid delays in diagnosis and tailored treatment. Full article

Background: Despite distinct etiologies, type 1 diabetes (T1D) and type 2 diabetes (T2D) share chronic inflammation as a core feature. Interleukins, key immune mediators, play important yet still not fully understood roles in the development and complications of both conditions. Objective: This narrative review aims to provide a comprehensive and critical synthesis of current evidence on the role of key interleukins in T1D and T2D, highlighting their immunological functions, genetic associations, clinical correlations, and translational potential. Methods: A targeted literature search was conducted in PubMed, Google Scholar, and ScienceDirect up to January 2025, focusing on English-language clinical and experimental studies involving interleukins and their relevance to T1D and T2D. Reference lists were manually screened for additional sources. Interleukins (ILs) were reviewed individually to assess their immunobiology, disease specificity, and biomarker or therapeutic value. Findings: Pro-inflammatory cytokines such as IL-1β, IL-6, and IL-17 contribute to islet inflammation, insulin resistance, and microvascular damage in both T1D and T2D. Anti-inflammatory mediators including IL-4, IL-10, and IL-13 exhibit protective effects but vary in expression across disease stages. Less-characterized interleukins such as IL-3, IL-5, IL-9, and IL-27 demonstrate dual or context-dependent roles, particularly in shaping immune tolerance and tissue-specific complications such as nephropathy and neuropathy. Polymorphisms in IL-10 and IL-6 genes further suggest genetic contributions to interleukin dysregulation and metabolic dysfunction. Despite promising insights, translational gaps persist due to overreliance on preclinical models and limited longitudinal clinical data. Conclusions: Interleukins represent a mechanistic bridge linking immune dysregulation to metabolic derangements in both T1D and T2D. While their diagnostic and therapeutic potential is increasingly recognized, future research must address current limitations through isoform-specific targeting, context-aware interventions, and validation in large-scale, human cohorts. A unified interleukin-based framework may ultimately advance personalized strategies for diabetes prevention and treatment. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as the leading cause of chronic liver disease worldwide, driven by the global epidemics of obesity, type 2 diabetes, and metabolic syndrome. In this evolving nosological landscape, alcohol consumption—traditionally excluded from the diagnostic criteria of non-alcoholic fatty liver disease (NAFLD)—has regained central clinical importance. The recently defined MetALD phenotype acknowledges the co-existence of metabolic dysfunction and a significant alcohol intake, highlighting the synergistic nature of their pathogenic interactions. This narrative review provides a comprehensive analysis of the biochemical, mitochondrial, immunometabolic, and nutritional mechanisms through which alcohol exacerbates liver injury in MASLD. Central to this interaction is cytochrome P450 2E1 (CYP2E1), whose induction by both ethanol and insulin resistance enhances oxidative stress, lipid peroxidation, and fibrogenesis. Alcohol also promotes mitochondrial dysfunction, intestinal barrier disruption, and micronutrient depletion, thereby aggravating metabolic and inflammatory derangements. Furthermore, alcohol contributes to sarcopenia and insulin resistance, establishing a bidirectional link between hepatic and muscular impairment. While some observational studies have suggested a cardiometabolic benefit of a moderate alcohol intake, emerging evidence challenges the safety of any threshold in patients with MASLD. Accordingly, current international guidelines recommend alcohol restriction or abstinence in all individuals with steatotic liver disease and metabolic risk. The review concludes by proposing an integrative clinical model and a visual cascade framework for the assessment and management of alcohol consumption in MASLD, integrating counseling, non-invasive fibrosis screening, and personalized lifestyle interventions. Future research should aim to define safe thresholds, validate MetALD-specific biomarkers, and explore the efficacy of multidisciplinary interventions targeting both metabolic and alcohol-related liver injury. Full article

In women, gonadal hormones play a crucial regulatory role in body fat distribution and glucose–lipidic homeostasis, which are closely associated with the hepatic steatogenesis and intrahepatic inflammatory pathways. Accumulating evidence supports the idea that hepatic health is closely linked to endocrine ovarian function through hormonal, metabolic, and immunological communications, collectively known as the “ovary–liver axis”. This review presents the molecular mechanisms involved in sex hormone synthesis, metabolism, and signaling pathways along the ovary–liver axis, focusing on dysregulated mechanisms that may contribute to common disorders and, specifically to hepatic derangements in the context of altered ovarian function. Additionally, we analyzed epidemiological evidence supporting the ovary–liver axis, specifically examining meta-analytic studies exploring the connection between polycystic ovary syndrome and metabolic dysfunction-associated steatotic liver disease (MASLD). We also discuss studies linking hypogonadism with liver health, with a specific focus on Turner syndrome and MASLD. Furthermore, we explore the impact of menopause on liver health. Our integrated molecular and epidemiological approach identifies important clinical and public health implications, aiming to uncover potentially innovative interventions and effective strategies for managing disease progression. However, unexplored areas within the ovary–liver axis highlight the need for further research on causal pathways. Full article

Introduction: Postoperative delirium (POD) remains a major complication in geriatric surgical care, with poorly understood molecular mechanisms. Emerging evidence links cardiac surgery to elevated markers of neurologic injury, even in cognitively intact individuals. While neuroinflammation is the prevailing model, a more detailed characterization of the systemic inflammatory and metabolic response to surgery may offer deeper insights into POD pathogenesis. Methods: We used the 7K SomaLogic proteomic platform to analyze preoperative and postoperative day-one serum samples from 78 patients undergoing cardiac surgery with cardiopulmonary bypass. We compared proteomic profiles within individuals (pre- vs. post-surgery) and between those who developed POD and those who did not. Functional analyses were performed to identify relevant biological pathways. A composite metabo-inflammatory score (MIF) was derived to quantify systemic derangement. We modeled the association between POD and age, sex, baseline cognition, and MIF score. Results: Cardiac surgery with CPB was associated with marked inflammatory responses across all subjects, including increased IL-6, CRP, and serum amyloid A. Compared to controls, POD cases showed greater metabo-inflammatory shifts from baseline (average logFC = 2.56, p < 0.001). Lower baseline cognitive scores (OR = 0.74, p = 0.019) and higher MIF scores (OR = 1.03, p = 0.013) were independently associated with increased POD risk. Conclusions: Cardiac surgery with CPB elicits a significant metabo-inflammatory response in all patients. However, those who develop POD exhibit disproportionately greater dysregulation. Full article

Gastric cancer remains a significant global health burden, with curative treatment relying on surgical resection, typically total or subtotal gastrectomy. However, the procedure frequently triggers acute metabolic and nutritional disturbances that may impact recovery. Objective: This prospective study aimed to investigate whether the type of gastrectomy (total vs. subtotal) influences early postoperative biochemical and hematological alterations, with particular attention to nutritional impact. Methods: A cohort of 295 patients (123 female, 172 male) who underwent gastrectomy for gastric cancer at the Institute of Oncology Iași (2023–2024) was evaluated. Laboratory parameters, including hemoglobin, hematocrit, lymphocyte and platelet counts, serum albumin, total protein, sodium, potassium, creatinine, and urea, were analyzed preoperatively and on postoperative day 14 using standard clinical methods. Results: Anemia was observed in over 90% of patients, irrespective of sex or procedure type. Electrolyte imbalances (notably hyponatremia and hypokalemia) and indicators of nutritional deficit (hypoalbuminemia, low creatinine) were highly prevalent, with a greater frequency among female patients. Total gastrectomy was associated with more severe biochemical and nutritional alterations compared to subtotal procedures. Conclusions: Total gastrectomy significantly exacerbates early postoperative metabolic and nutritional derangements. These findings reinforce the need for proactive, personalized postoperative nutritional and electrolyte management strategies to support recovery and reduce complication risks. Full article

Background: There are known associations between periodontitis and colorectal cancer, but knowledge on the connections existing between the two are not fully understood. The aim of our study was to assess prevalence and clinical severity of periodontitis in patients with localized colorectal cancer. Secondly, the dynamics of metabolic derangements, particularly glucose metabolism, insulin resistance, and diabetes mellitus were studied as well. Methods: Diagnostic procedures included endoscopies with patohistology, laboratory exams, the insulin resistance homeostatic model assessment method (HOMA index), anthropometrics, and radiology imaging. Periodontal status was evaluated by full-mouth periodontal examination. Results: A total of 79 patients with localized colorectal carcinoma, with slight male predominance of 55.7%, and an age of 65.7 ± 12.4 years participated in this study. Three-quarters of patients (73.4%; 95% CI: 63.0–82.2%) were diagnosed with periodontitis. Patients with periodontitis and colorectal cancer had significantly increased glucose levels (fasting and after oral glucose challenge), (both p < 0.05). Also, increased values of the HOMA index were found in patients with periodontitis vs. controls (without periodontitis) and colorectal cancer; 6.38 ± 5.74 vs. 3.58 ± 2.6 (p = 0.012); Spearman’s Rho correlation coefficient = 0.271 (p = 0.039). There were significant differences in high-density cholesterol in patients with periodontitis vs. controls, 1.41 ± 0.28 vs. 1.23 ± 0.35 mmol/L (p = 0.016), but correlations were insignificant; Rho c.c. = 0.045 (p = 0.738). Conclusions: The most consorted connections between periodontitis and colorectal cancer were found among parameters of metabolic domain, especially glucose concentrations and insulin resistance. Further studies, which would include novel and emerging antidiabetic treatments and their effects on the prevention or control of both diseases, would be warranted. Full article

Over the past two decades, metabolic syndrome (MetS) and infections caused by multidrug-resistant (MDR) pathogens have emerged as converging global health challenges. Traditionally investigated as separate entities, accumulating evidence increasingly supports a bidirectional relationship between them, mediated by chronic inflammation, immune dysregulation, gut microbiota alterations, and antibiotic-driven expansion of the resistome. This narrative review examines the complex immunometabolic interplay linking MetS and MDR infections, focusing on molecular mechanisms, clinical implications, and prospective research directions. A systematic literature search was conducted using major databases, including PubMed and Scopus, targeting studies from the last 15 years that explore the interface between metabolic dysfunction and antimicrobial resistance. Particular attention is given to key immunometabolic pathways such as the IRS–PI3K–AKT–mTOR axis; the contribution of visceral adiposity and Toll-like receptor (TLR)-mediated inflammation; and the role of gut dysbiosis in augmenting both susceptibility to infections and metabolic derangements. Evidence is presented supporting the hypothesis that MetS increases host vulnerability to MDR pathogens, while chronic MDR infections may reciprocally induce systemic metabolic reprogramming. Viral infections with established metabolic sequelae (e.g., HIV, hepatitis C virus [HCV], and cytomegalovirus [CMV]) are also considered to broaden the conceptual framework. Although current data remain largely associative and fragmented, the emerging MetS–MDR syndemic model poses substantial challenges for translational research, antimicrobial stewardship, and personalized therapeutic strategies. Recognizing this reciprocal relationship is pivotal for refining infection risk stratification, optimizing treatment, and informing public health policies. Further investigations are warranted to elucidate the magnitude and directionality of this association and to identify predictive immunometabolic biomarkers that may guide targeted interventions in high-risk populations. Full article

In humans, heart failure (HF) and cancer are among the leading causes of morbidity and mortality. A growing body of evidence highlights a bidirectional relationship between these conditions, underpinned by shared risk factors and overlapping pathophysiological pathways. This review aims to explore the emerging role of the intestinal microbiome as a common mechanistic link between HF and cancer. Specifically, we examine how microbial dysbiosis and its metabolic products—such as trimethylamine N-oxide (TMAO), short-chain fatty acids (SCFAs), bile acids, lipopolysaccharides (LPS), and branched-chain amino acids (BCAAs)—contribute to inflammation, immune dysregulation, oxidative stress, and metabolic dysfunction. These mechanisms promote multiorgan impairment and establish a vicious cycle that fuels both tumorigenesis and cardiac deterioration. HF, cancer, and the gut microbiome are not isolated entities but are deeply interconnected through shared biological mechanisms—including chronic inflammation, microbial dysbiosis, immune and neurohumoral modulation, and metabolic derangement. These findings support the concept of a microbiome-centered axis involving the gut, heart, and tumors, which may underlie many chronic disease processes. Understanding these interactions may provide novel insights into disease pathogenesis and uncover promising therapeutic targets that leverage microbiome modulation to prevent or treat HF, cancer, and other systemic diseases. Full article

Background: The pathophysiological mechanisms underlying altered plasma glutamine concentrations in sepsis remain poorly understood. Identifying clinical, immunological, and metabolic correlates of glutamine fluctuations is crucial to advancing precision medicine, developing targeted therapies, and improving survival outcomes in septic patients. Methods: We enrolled 469 patients with sepsis and assessed inflammatory markers—including body temperature, white blood cell count, and C-reactive protein levels—upon admission to the internal medicine unit. Lymphocyte count and plasma concentrations of glutamine, glutamic acid, 5-oxoproline, phenylalanine, tyrosine, and leucine were measured using gas chromatography–mass spectrometry. Patients were stratified into three groups based on plasma glutamine levels. Mortality was recorded at 30 days and 6 months. Results: Low, intermediate, and high glutamine levels were observed in 46% (n = 217), 47% (n = 218), and 7% (n = 34) of patients, respectively. Patients with hyperglutaminemia exhibited significantly lower body temperature, white blood cell and lymphocyte counts, C-reactive protein levels, and glutamic acid-to-5-oxoproline ratio (a surrogate marker of glutathione availability), along with elevated phenylalanine levels, leucine levels, and tyrosine-to-phenylalanine ratio (all p < 0.01). Metabolic disruption and mortality increased progressively across glutamine level groups. Kaplan–Meier analysis demonstrated significantly higher mortality in patients with elevated glutamine levels at both 30 days (log-rank p = 0.03) and 6 months (log-rank p = 0.05). Conclusions: At baseline, increasing plasma glutamine levels are associated with progressively deeper lymphopenia, more pronounced metabolic derangement, and higher short- and long-term mortality in patients with sepsis. Full article

Background/Objectives: Critically ill patients can often present acid–base alterations. The aim of this study was to evaluate the prevalence and the time-course of acid–base alterations on intensive care unit (ICU) admission and on day one by the traditional standard base excess (SBE)-based and the Stewart methods in mechanically ventilated patients. Methods: A prospective observational study enrolling mechanically ventilated patients in the ICU was conducted. Arterial blood gas analysis, blood and urine samples were obtained on ICU admission and on day one. Plasmatic and urinary acid–base variables were compared among acidemic, alkalemic and patients with normal pH. The agreement between the SBE-based and Stewart methods was assessed at ICU admission and on day one. Results: One hundred and seventy-two patients were enrolled. On ICU admission, 55 (32%), 29 (17%) and 88 (51%) patients had acidemia, alkalemia and a normal pH, respectively. On day one, 12 (7%), 48 (28%) and 112 (65%) patients had acidemia, alkalemia and a normal pH with lower values of paCO2 and albumin. According to the SBE and Stewart approaches, the occurrence of metabolic acidosis was similar (24% vs. 35%), as well as the rate of metabolic alkalosis (16% vs. 23%) on ICU admission; on day one, the occurrence of metabolic acidosis was different (12% vs. 35%), as well as the rate of metabolic alkalosis (35% vs. 14%). The agreement between methods was estimated to be low both on ICU admission and on day one. Conclusions: Up to 50 % of mechanically ventilated patients presented acid–base derangements, mainly due to acidemia on ICU admission and to alkalemia after 24 h, secondary to alterations in carbon dioxide and plasma albumin. The agreement between the traditional and Stewart approaches was poor. The Stewart approach could be more accurate in detecting the acid–base disturbances in critically ill patients characterized by changes of mechanical ventilation and fluid administration. Full article

Emerging research suggests that the intrauterine environment plays a critical role in predisposing individuals to metabolic syndrome (MetS), a constellation of conditions that heightens the risk for heart disease, stroke, and diabetes. Traditionally linked to lifestyle, the risk for MetS is now understood to be also influenced by fetal exposures. The environment in which a child lives offers abundant potential sources that can contribute to an increased risk of developing various diseases, and in some cases, these factors can be avoided. This review integrates findings from both epidemiological and experimental research to underscore the impact of prenatal factors, including maternal nutrition, obesity, gestational diabetes (GDM), and birth size, on the subsequent development of metabolic derangements in offspring, particularly during puberty. The progression of genetic and epigenetic studies has enlightened the pathophysiology of these conditions starting in the intrauterine period and continuing into early life. By examining data and studies, this article elucidates the prenatal influences and underlying mechanisms that contribute to the pathogenesis of MetS. The updated understanding of the link between the intrauterine environment and future health comorbidities will draw attention to intrauterine care and maternal health and contribute to the prevention of serious diseases in adulthood. Full article

Background/Objectives: Inborn errors of metabolism (IEMs) represent a diverse group of genetic disorders characterized by enzymatic defects that disrupt metabolic pathways, leading to toxic metabolite accumulation, deficits, or impaired macromolecule synthesis. While strict dietary interventions are critical for managing many of these conditions, hormonal and metabolic changes during puberty introduce new challenges. Advancements in early diagnosis and treatment have significantly extended the lifespan of individuals with IEMs. However, this increased longevity is associated with heightened risks of new medical problems, including obesity, insulin resistance, and type 2 diabetes mellitus (T2DM), as these complications share mechanistic features with those seen in obesity and T2DM. Methods: This mini-review examines current knowledge of the intricate interplay between pubertal hormones and metabolic pathways in IEM patients. Results: We address critical questions, such as if puberty intensifies the risk of metabolic derangements in these individuals and if there is a metabolic intersection where these disorders converge, leading to shared complications. We highlight the impact of puberty-induced hormonal fluctuations, such as growth hormone (GH) surges and sex steroid activity, on disorders like phenylketonuria, urea cycle defects, and fatty acid oxidation disorders. Moreover, we explore the role of dietary interventions in mitigating or exacerbating these effects, emphasizing the importance of balancing nutritional needs during growth spurts. Conclusions: A multidisciplinary approach integrating endocrinology, nutrition, and emerging therapies is advocated to optimize metabolic health during puberty. Addressing these challenges is critical for improving long-term outcomes for individuals with IEMs, particularly during this pivotal developmental phase. Full article

Obesity is commonly associated with metabolic diseases including type 2 diabetes, hypertension, and dyslipidemia. Moreover, individuals with obesity are at increased risk of cardiovascular disease. However, a subgroup of individuals within the obese population presents without concurrent metabolic disorders. Even though this group has a stable metabolic status and does not exhibit overt metabolic disease, this status may be transient; these individuals may have subclinical metabolic derangements. To investigate the latter hypothesis, an analysis of the proteome signature was conducted. Plasma samples from 27 subjects with obesity but without an associated metabolic disorder (obesity only (OBO)) and 15 lean healthy control (LHC) subjects were examined. Fasting samples were subjected to Olink proteomics analysis targeting 184 proteins enriched in cardiometabolic and inflammation pathways. Our results distinctly delineated two groups with distinct plasma protein expression profiles. Specifically, a total of 24 proteins were differentially expressed in individuals with obesity compared to LHC. Among these, 13 proteins were downregulated, whereas 11 proteins were upregulated. The pathways that were upregulated in the OBO group were related to chemoattractant activity, growth factor activity, G protein-coupled receptor binding, chemokine activity, and cytokine activity, whereas the pathways that were downregulated include regulation of T cell differentiation, leukocyte differentiation, reproductive system development, inflammatory response, neutrophil, lymphocyte, monocyte and leukocyte chemotaxis, and neutrophil migration. The study identifies several pathways that are altered in individuals with obesity compared to healthy control subjects. These findings provide valuable insights into the underlying mechanisms, potentially paving the way for the identification of therapeutic targets aimed at improving metabolic health in individuals with obesity. Full article

The increasing prevalence of the spectrum of Steatotic Liver Disease (SLD), including Metabolic-Associated Steatotic Liver Disease (MASLD), Metabolic-Associated Steatohepatitis (MASH), and progression to Cirrhosis and Hepatocellular Carcinoma (HCC) has led to intense research in disease pathophysiology, with many studies focusing on the role of iron. Iron overload, which is often observed in patients with SLD as a part of metabolic hyperferritinaemia (MHF), particularly in the reticuloendothelial system (RES), can exacerbate steatosis. This imbalance in iron distribution, coupled with a high-fat diet, can further promote the progression of SLD by means of oxidative stress triggering inflammation and activating hepatic stellate cells (HSCs), therefore leading to fibrosis and progression of simple steatosis to the more severe MASH. The influence of iron overload in disease progression has also been shown by the complex role of ferroptosis, a type of cell death driven by iron-dependent lipid peroxidation. Ferroptosis depletes the liver’s antioxidant capacity, further contributing to the development of MASH, while its role in MASH-related HCC is potentially linked to alternations in the tumour microenvironment, as well as ferroptosis resistance. The iron-rich steatotic hepatic environment becomes prone to hepatocarcinogenesis by activation of several pro-carcinogenic mechanisms including epithelial-to-mesenchymal transition and deactivation of DNA damage repair. Biochemical markers of iron overload and deranged metabolism have been linked to all stages of SLD and its associated HCC in multiple patient cohorts of diverse genetic backgrounds, enhancing our daily clinical understanding of this interaction. Further understanding could lead to enhanced therapies for SLD management and prevention. Full article