Search Results (2,372)

Background/Objectives: Systemic lupus erythematosus (SLE) is an autoimmune disease affecting multiple organ systems, characterized by remissions and relapses. Musculoskeletal involvement occurs in up to 95% of patients and may present as the initial symptom in 50%. Such involvement is often subclinical, without obvious joint or tendon inflammation. Musculoskeletal ultrasound (US) has proven valuable for detecting pathological changes in joints and periarticular structures, including in SLE patients, and early detection, particularly in subclinical stages, supports optimal therapy, monitoring, and improved prognosis. This study aimed to determine the frequency of new clinical manifestations in patients with previously confirmed clinical and subclinical musculoskeletal inflammation after 2 and 5 years, and to evaluate associations with sex, age, BMI, smoking status, ESR, CRP, SLEDAI-2K, complement components C3 and C4, anti-dsDNA antibodies concentrations, and prior treatment. Methods: The study included 34 SLE patients with clinical and 22 with subclinical musculoskeletal inflammation, confirmed at baseline by history, examination, and US. Follow-up at 2 and 5 years recorded new clinical manifestations. Correlations with patient characteristics were assessed to identify predictors. Results: New clinical manifestations occurred in 34% of patients at 2 years and 48% at 5 years, most commonly cutaneous, musculoskeletal, and hematological. Summary analysis identified female sex, lower BMI, and lower baseline SLEDAI-2K scores as the strongest predictors. In the subclinical group, female sex, smoking, and lower SLEDAI-2K scores were predictive, while in the clinical group, female sex, lower SLEDAI-2K scores, lower ESR, and higher anti-ds DNA levels were associated with new manifestations. Conclusions: Female sex, lower BMI, and lower baseline SLEDAI-2K scores are key predictors of new clinical manifestations in SLE patients, highlighting the importance of early detection and individualized monitoring, particularly in patients with subclinical musculoskeletal inflammation. Full article

The nitric oxide (NO) pathway is a fundamental regulator of vascular tone, myocardial function, and inflammation. In heart failure (HF), especially in advanced stages, dysregulation of NO–soluble guanylate cyclase (sGC)–cyclic guanosine monophosphate (cGMP) signaling contributes to endothelial dysfunction, increased vascular resistance, myocardial fibrosis, and impaired cardiac performance. Chronic inflammation further reduces NO bioavailability, exacerbating HF progression This review synthesizes current knowledge on the role of the NO pathway in HF pathophysiology, with a focus on stable and advanced HF. Special attention is given to patient subgroups with comorbidities such as chronic kidney disease, where modulation of NO signaling may be particularly beneficial. We also evaluate therapeutic strategies targeting NO bioavailability and sGC stimulation. Evidence shows that impaired NO signaling promotes systemic and pulmonary vasoconstriction, elevates ventricular afterload, and worsens cardiac remodeling. Pharmacological agents that restore NO levels or activate downstream effectors such as sGC improve vasodilation, reduce fibrosis, and enhance myocardial relaxation. These effects are especially relevant in advanced HF patients and those with renal impairment, who often exhibit limited responses to conventional therapies. The NO pathway represents a promising therapeutic target in both stable and advanced HF. Modulating this pathway could improve outcomes, particularly in complex populations with multiple comorbidities, highlighting the need for further clinical research and tailored treatments. Full article

In chronic kidney disease (CKD), oxidative stress and inflammation contribute to disease progression and CKD-related morbidity. The nuclear factor erythroid 2-related factor 2 (Nrf2) system plays a central role in the cellular response to oxidative and inflammatory stress. In this brief report, we describe our investigation into whether alterations in the gene expression of key Nrf2 pathway components contribute to the endogenous activation of the Nrf2 system previously reported in less advanced CKD. To this end, we quantified the gene expression of Nrf2, its regulatory protein Kelch-like ECH-associated protein 1 (KEAP1), and the Nrf2 downstream target NAD(P)H:quinone oxidoreductase 1 (NQO1) in monocytes from patients in different stages of CKD. We observed significantly elevated NQO1 gene expression in CKD stage G3b compared to CKD stages G1-3a (p < 0.05), G4 (p < 0.01), and G5 (p < 0.001). In contrast, the gene expression levels of Nrf2 and KEAP1 did not differ significantly between CKD stages. These findings suggest that endogenous activation of the Nrf2 system in moderate CKD predominantly reflects functional activation, likely at the protein level, rather than changes in the gene expression of Nrf2 or KEAP1. Full article

Chronic kidney disease (CKD) affects nearly 10% of the global population, ranks among the top ten causes of death, and often progresses silently to end-stage disease without timely intervention. Increasing evidence indicates that many adult-onset cases originate in early life through adverse influences on kidney development, a process termed kidney programming within the Developmental Origins of Health and Disease (DOHaD) framework. Environmental pollutants are now recognized as key drivers of kidney injury across the life course. Heavy metals, air pollutants, plastic contaminants such as bisphenol A, phthalates, and micro/nanoplastics—as well as biocontaminants like mycotoxins and aristolochic acid—and chronic light pollution can accumulate in kidney tissue or act systemically to impair function. These exposures promote oxidative stress, inflammation, and endothelial and circadian disruption, culminating in tubular injury, glomerular damage, and fibrosis. Notably, early-life exposures can induce epigenetic modifications that program lifelong susceptibility to CKD and related complications. Oxidative stress is central to these effects, mediating DNA, lipid, and protein damage while influencing developmental reprogramming during gestation. Preclinical studies demonstrate that antioxidant-based interventions may mitigate these processes, providing both renoprotective and reprogramming benefits. This review explores the mechanistic links between environmental pollutants, oxidative stress, and kidney disease and highlights antioxidant strategies as promising avenues for prevention and intervention in vulnerable populations. Full article

Background: Chronic kidney disease (CKD) in companion animals leads to progressive renal deterioration and metabolic complications such as hyperphosphatemia and metabolic acidosis, particularly in advanced stages. Methods: This 90-day, double-blind, randomized controlled study evaluated the effects of a renal supplement (Renal Combi, Candioli srl, Beinasco, Turin, Italy) in 30 dogs diagnosed with CKD. Dogs were randomly assigned to a treatment group (TRT, n = 15), receiving a commercial renal diet plus the supplement (once daily), or a control group (CTR, n = 15), receiving the same diet and a placebo. Results: Results showed that supplementation effectively reduced proteinuria, blood urea, and phosphorus levels, stabilized creatinine and SDMA, and maintained blood pressure. It also improved markers of systemic inflammation and oxidative stress. Conclusions: The once-daily dosage simplified administration and was especially beneficial for hyporexic dogs or those on multiple medications. This study supports the use of the tested supplement as an effective adjunctive therapy for managing CKD in dogs, offering metabolic, renal, and nutritional benefits while enhancing compliance through convenient dosing. Full article

Positioned at the intersection of sex medicine and endocrinology, metabolic dysfunction-associated steatotic liver disease (MASLD) is often managed by specialists who may not be fully familiar with the complex roles of sex hormones in its pathogenesis and clinical course. To address this gap, we review the molecular actions of testosterone, estradiol, and progesterone on liver functions, as well as the role of sex-hormone binding globulin (SHBG) in MASLD histogenesis, highlighting disparities by sex as well as reproductive status. We also discuss how sex hormones influence fatty acid metabolism, gut dysbiosis, mitochondrial activity, gluco-lipidic homeostasis, lipotoxicity, inflammation, and MASLD-related liver tumorigenesis. Furthermore, we examine observational studies on associations between endogenous and exogenous sex hormones and SHBG with MASLD, with attention to hypogonadism in either sex or polycystic ovary syndrome. We summarize the role of sex hormones in modulating MASLD risk across life stages such as menopause, breastfeeding, and lactation. Lastly, we review the hepatic effects of hormone replacement therapy (HRT) on MASLD in both sexes, prospects, and safety of HRT and contraceptives among individuals with chronic liver disease. In conclusion, sex hormones play significant roles in MASLD pathobiology, underscoring the importance of sex-specific approaches in clinical practice and research. Full article

Leishmaniasis is a parasitic disease caused by Leishmania spp., transmitted by sandflies, and endemic in 98 countries. Leishmania infantum, the main agent of visceral leishmaniasis in Europe, commonly infects both humans and animals, with dogs as the principal domestic reservoir. Clinical manifestations in dogs depend on the host immune response. A robust Th1 response facilitates macrophage activation and parasite control, while persistently elevated TNF-α and IL-6 can lead to chronic inflammation and tissue damage. Current treatments reduce parasite load but rarely achieve complete cure and are often associated with relapses and resistance. Artemisia annua, source of artemisinin, could be a promising alternative to canine leishmaniasis. Despite its potential, no published studies have investigated its effect specifically against Leishmania infantum as well as its possible dual action: antiparasitic and immunomodulation. We conducted in vitro evaluations of a standardized Artemisia annua extract. Leishmanicidal activity was assessed against both promastigote and amastigote stages, and cytokine modulation was evaluated in RAW 264.7 macrophages. The extract showed strong leishmanicidal activity without cytotoxicity and significantly reduced TNF-α and IL-6 levels under inflammatory conditions, and in both cases, efficiency was correlated with artemisinin content. These results support Artemisia annua as a promising safer therapeutic adjuvant candidate for canine leishmaniasis, targeting both the parasite and the host inflammatory response. Full article

Background/Objective: Systemic inflammation is a hallmark of end-stage renal disease (ESRD) and contributes to the high burden of cardiovascular morbidity and mortality in hemodialysis (HD) patients. The systemic immune–inflammation index (SII), derived from peripheral neutrophil, lymphocyte, and platelet counts, has emerged as a promising biomarker of immune–inflammatory status. This study aimed to assess the acute effect of a single HD session on systemic inflammation and to identify metabolic predictors associated with this response. Methods: In this single-center observational before–after study, 44 chronic HD patients were enrolled. Blood samples were collected immediately before and after a single HD session. SII was calculated as platelet count × neutrophil count/lymphocyte count. Subgroup analyses were conducted based on renal disease etiology and diabetic status. Multivariable linear regression models identified baseline predictors of SII variation. Results: Median SII significantly decreased post-HD in the overall cohort (from 553.4 [342.6–847.5] to 449.1 [342.6–866.6], p = 0.001), with a more pronounced reduction in patients with cardiometabolic etiologies (from 643.4 [353.3–1360.0] to 539.1 [324.8–1083.4], p = 0.007) and diabetes (from 671.1 [408.7–1469.1] to 458.3 [285.7–1184.4], p = 0.028), but not in those with nephroangiosclerosis (p = 0.182). Baseline total cholesterol (p = 0.001) and gamma-glutamyl transferase (p = 0.034) were positively associated with smaller reductions in SII, while higher baseline glycaemia predicted a greater decrease in post-dialysis SII (p = 0.021). Conclusions: HD acutely modulates systemic inflammation, as reflected by reduction in SII. The magnitude of this response is significantly influenced by individual metabolic profiles. These findings highlight the relevance of metabolic–immune crosstalk in ESRD and suggest that SII may serve as a dynamic biomarker integrating inflammatory and metabolic signals, deserving further validation in larger, outcome-driven studies. Full article

Introduction: Sepsis-induced cardiac dysfunction (SICD) is a transient cardiac disfunction, with variable described prevalence and uncertain prognostic. This study aimed to characterize the laboratory and microbiological findings in critically ill patients with sepsis who developed left ventricular (LV) or biventricular systolic dysfunction. Methods: Patients who required intensive care unit hospitalization for sepsis were screened retrospectively. Only patients with positive cultures and echocardiography performed within 24 h from admission were included. The exclusion criteria were infective endocarditis, acute coronary syndrome, history of cardiomyopathy, severe valve disease, end-stage organ or oncological disease. Cardiac function was appreciated on transthoracic echocardiography, using LV ejection fraction for the left ventricle and tricuspid annular plane systolic excursion (TAPSE) for the right ventricle. SICD was confirmed if the systolic dysfunction found upon admission was reversible within 7–10 days. Results: A total of 100 patients with positive cultures were included. The median age was 73 and 55% were male. SICD was diagnosed in 14% of patients. Patients with SICD were more likely to develop septic shock and had longer hospital and intensive care unit stay. In-hospital mortality was 44% with no significant difference between SICD and non-SICD patients. Laboratory markers upon hospital admission showed that SICD patients had significantly higher values of lactate and transaminases. Cardiac (troponin and NT-proBNP) and inflammation markers (leukocytes, neutrophils, NLR, C-reactive protein, procalcitonin) had higher values in patients with SICD but the difference did not reach statistical significance. Streptococcal infections and polymicrobial cultures were risk factors for developing SICD. Higher rates of infections with Enterobacterales were seen in the SICD group but the difference was not significant. Conclusions: SICD patients had higher lactate, inflammation, and cardiac biomarkers levels upon admission and significantly higher rates of streptococcal infections and polymicrobial cultures. Full article

Living kidney transplantation offers the best results for end-stage renal disease patients, but concerns about cardiovascular risk after nephrectomy for kidney donors have been raised. We aimed to estimate the contribution of renal function to endothelial dysfunction (ED) and subclinical inflammation in a non-interventional, prospective, multicenter, longitudinal study with two cohorts: living kidney donors and their transplant recipients (registered clinical trial NCT02515643). The measured glomerular filtration rate (mGFR) by iohexol clearance, estimated GFR according to the CKD-EPI and MDRD-4 formulas, and levels of endothelial dysfunction (sVCAM-1, sICAM-1, E-selectin, von Willebrand Factor, pentraxin, and urinary albumin-to-creatinine ratio) and subclinical inflammation biomarkers (sIL-6, sTNF-R1, sTNF-R2, sTWEAK, and high-sensitivity C-reactive protein) were determined at baseline and 1-year follow-up. Fifty pairs of donors and recipients were recruited between 2015 and 2018. Among the endothelial dysfunction biomarkers, sVCAM-1 increased in donors and decreased in recipients (p < 0.01) while, among the inflammation biomarkers, sTNFR1 and sTNFR2 significantly increased in donors and decreased in recipients (p < 0.001). After transplantation, parallel increases and decreases in ED and subclinical inflammation biomarkers were observed in the donor and recipient cohorts, respectively. Long-term follow-up is needed to characterize the cardiovascular risk associated with these changes. Full article

Background/Objectives: Diabetic nephropathy (DN) is a major complication of diabetes and a leading cause of end-stage renal disease, a condition associated with high mortality risks. Recently, supplementation with probiotics and postbiotics has been attracting attention. Especially, metabolites of natural products bioconverted by beneficial bacteria have emerged as a novel therapeutic intervention for metabolic diseases, including diabetes, due to the enhanced bioavailability of their metabolites. This study investigated the alleviating effects of metabolites derived from guava leaf extract bioconverted by Limosilactobacillus fermentum (GBL) on renal inflammation in type 2 diabetic mice. Methods: For this purpose, diabetes was induced in male C57BL/6J mice by a high-fat diet and streptozotocin injection (80 mg/kg BW) twice. Subsequently, mice with fasting blood glucose levels higher than 300 mg/dL were administered metabolites of L. fermentum (LF) (50 mg/kg BW/day) or guava leaf extract bioconverted by L. fermentum (GBL) (50 mg/kg BW/day) by oral gavage for 15 weeks. Results: GBL demonstrated potential in alleviating hyperglycemia-induced DN in diabetic mice. It markedly improved hyperglycemia, glucose tolerance, and morphological alterations, which might stem from activation of key regulators of energy metabolism. GBL uniquely reduced advanced glycation end products (AGEs) and suppressed nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)-driven inflammatory pathways, which significantly alleviated oxidative stress and apoptosis. Conclusions: This highlights the distinct therapeutic efficacy of GBL in addressing DN, primarily through its effects on renal inflammation. Taken together, GBL can be used as a promising nutraceutical to mitigate hyperglycemia and its associated renal inflammation, thereby alleviating the progression of DN. Full article

Furunculosis caused by Aeromonas salmonicida is one of the most common diseases in aquaculture, leading to significant economic losses. This study comprehensively investigated the dynamics of pathophysiological and histopathological disorders in rainbow trout (Oncorhynchus mykiss) infected with the moderately virulent strain A. salmonicida SL0n. Whole-genome analysis showed that strain SL0n belongs to the A. salmonicida species complex, possessing a single circular chromosome. The genome encodes a wide range of virulence factors, including adhesion systems (type IV pili, fimbriae), toxins (aerolysin, hemolysins), and a type II secretion system (T2SS), but notably lacks plasmids and a type III secretion system (T3SS). This genomic profile likely dictates a pathogenic mechanism reliant on secreted exotoxins (via T2SS), explaining the observed systemic cytotoxic damage. In an acute experiment, the 4-day LD₅₀ was determined to be 1.63 × 10⁶ CFU/fish. In a prolonged experiment, fish were injected with a sublethal dose (1.22 × 10⁶ CFU/fish—75% of LD50). The disease progressed through three consecutive stages. The early stage (1–2 DPI) was characterized by maximal bacterial load and activation of nonspecific immunity. The acute stage (4 DPI) manifested as severe septicemia and anemia, associated with systemic organ damage, which correlated with peak AST and ALT enzyme activity. The recovery stage (6 DPI) was marked by partial regression of inflammation, key biochemical and histological parameters indicated persistent liver and kidney dysfunction, signifying an incomplete recovery. These results demonstrate the pathogenesis of acute furunculosis and reveal that the genomic profile of the SL0n strain causes a sequential, systemic infection characterized by severe organ dysfunction. Full article

Background/Objectives: Chronic kidney disease (CKD) progression is strongly influenced by systemic inflammation. The neutrophil-to-lymphocyte ratio (NLR), derived from routine blood counts, reflects the balance between innate and adaptive immunity and has been proposed as a marker of adverse renal outcomes. We hypothesized that elevated baseline NLR is associated with reduced kidney function and increased risk of progression to end-stage kidney disease (ESKD) in adults with non-dialysis CKD. Methods: Following PRISMA guidelines, we systematically searched MEDLINE, Embase, and Scopus for studies enrolling adults with CKD stages 1–4 that reported renal outcomes according to baseline NLR. The primary outcome was progression to ESKD or renal replacement therapy (RRT) initiation. Results: Six eligible studies were identified, of which four provided sufficient data for meta-analysis. Across cohorts, elevated baseline NLR was consistently associated with adverse renal outcomes. In pooled analyses, high NLR nearly doubled the risk of ESKD or RRT (RR 1.96, 95% CI 1.30–2.97). Leave-one-out sensitivity analysis strengthened the association while reducing heterogeneity. For kidney function, higher NLR was associated with lower baseline eGFR (SMD −1.59, 95% CI −2.38 to −0.80). Conclusions: Elevated NLR is a robust prognostic marker of renal function decline and progression to ESKD or RRT in non-dialysis CKD. As a simple and inexpensive biomarker, NLR offers additional predictive value beyond eGFR and albuminuria. Incorporating NLR into risk models may refine stratification, guide follow-up, and enable earlier therapeutic optimization. Prospective large studies are warranted to establish thresholds and validate its role in clinical practice. Full article

Introduction: Cancer cachexia is associated with systemic inflammation and metabolic derangement, leading to muscle atrophy, which affects over 80% of pancreatic cancer patients, the highest rate among all malignancies, negatively impacting quality of life and significantly reducing survival rate. Malnutrition, skeletal muscle loss (sarcopenia), and imbalanced energy expenditure are indicators of cachexia. No established screening tools in clinical practice are specific and sensitive enough to detect pancreatic cancer in its early stages. Objective: This paper aims to provide new insights by examining contributing factors in the development of cachexia and exploring future directions for managing cachexia to improve quality of life and overall survival in patients with pancreatic cancer. Conclusions: It is clinically vital to identify nutritional risks and consider aggressive nutritional interventions as soon as pancreatic cancer is diagnosed to (1) stabilize body weight, (2) decrease the disease-associated burden, and (3) improve the quality of life. To support the clinical management of cachexia in this population, more research is needed. Specifically, research is needed to identify biomarkers, such as muscle fiber-related genes, optimize drug delivery tailored to the specific metabolic and molecular profile, combine chemotherapeutic agents with nutritional supplements, and consider non-pharmacological interventions such as acupuncture and exercise specifically for cancer-cachexia patients. A multifaceted approach will help achieve a better quality of life and prolonged overall survival in patients with pancreatic cancer. Full article

Background: Uraemic cardiomyopathy (UCM), the cardiac manifestation of chronic kidney disease, represents a significant clinical challenge that is often underdiagnosed despite being one of the strongest predictors of mortality in the chronic kidney disease (CKD) population. It develops through pathophysiological mechanisms unique to the uraemic state—left ventricular hypertrophy, myocardial fibrosis, and diastolic dysfunction—that often progress silently, sometimes even without traditional cardiovascular risk factors. Purpose: This review synthesises nephrology-centric mechanisms with clinical phenotypes and contemporary imaging (including CMR T1/T2 mapping and ECV), and proposes a CKD-stage–tailored diagnostic–therapeutic framework. It offers a distinct perspective by integrating the complex pathophysiology of UCM with practical diagnostic approaches and evolving management strategies, differentiating it from prior cardiology-focused overviews. Methods: A comprehensive literature search was conducted across Ovid MEDLINE, Embase, PubMed, Google Scholar, BMJ Best Practice, and UpToDate for studies published up to March 2025. Key findings were extracted from the final evidence set and manually verified for relevance. This review introduces a patho-mechanical cascade model of uraemic cardiomyopathy, integrating toxin-driven, metabolic, and haemodynamic axes. Nephrology-led screening protocols are proposed, leveraging proteomics and strain echo, and advocate mineralocorticoid receptor antagonists with sodium–glucose co-transporter-2 (SGLT2) inhibitor initiation at CKD Stage 3a. Cardiorenal clinics are essential for improved outcomes. Key Insights: UCM develops from a multifactorial process. This involves neurohormonal activation, oxidative stress, chronic inflammation, and exposure to toxins such as indoxyl sulfate and p-cresyl sulfate, arising from uraemia. Diagnosis is challenging, masked by overlapping features of fluid overload and anaemia. SGLT2 inhibitors, non-steroidal mineralocorticoid antagonists, and renin–angiotensin–aldosterone system modulation offer promising interventions. The effect of the dialysis modality, its timing, and renal transplantation on cardiac remodelling also emerging from recent studies. Conclusions: UCM sits at the intersection of two failing organ systems. Managing it effectively requires a paradigm shift to incorporate pharmacological and early diagnostic interventions and the integration of cardiology and nephrology care, and the timely implementation of interventions. Full article