Search Results (1,308)

Periodontitis is a biofilm-associated inflammatory disease that still requires effective local non-antibiotic antibacterial strategies. In this study, we developed a protonated defect-engineered atomic-layered graphitic carbon nitride nano-system (PVCN) for visible light photodynamic antibacterial therapy. Defect engineering was used to improve visible light absorption and photodynamic activity, while protonation introduced a positively biased surface potential to strengthen bacteria–material interactions and enhance interfacial antibacterial efficacy. Under visible light irradiation, PVCN showed increased ROS production, stronger bacterial adhesion, and rapid killing activity against both Staphylococcus aureus and Escherichia coli, with bactericidal efficiency above 95%. PVCN also disrupted S. aureus biofilms and induced membrane damage, intracellular content leakage, and metabolic suppression. Atomic force microscopy and omics analyses further supported enhanced bacterial adsorption as an important contributor to the improved antibacterial efficacy of PVCN. In vitro assays demonstrated preliminary cytocompatibility and hemocompatibility. In a ligature-induced mouse periodontitis model, PVCN reduced bacterial burden, alleviated inflammation, and attenuated alveolar bone loss. These results support PVCN as a promising photodynamic antibacterial material with preliminary therapeutic potential in experimental periodontitis, and highlight bio-interface regulation as a useful strategy for designing efficient carbon nitride-based photodynamic antibacterial materials. Full article

The bark of Myrica rubra (Lour.) Siebold & Zucc (M. rubra) is a natural remedy widely used in China and other Asian countries to treat tissue and bone injuries, burns, scalds, gastrointestinal ulcers, and diarrhea. Myricanol is an important ingredient in the bark of M. rubra. This review summarizes articles published over the past 26 years on the pharmacological effects and mechanisms of action of myricanol, aiming to advance research and applications of myricanol. Evidence shows that myricanol has multiple bioactive properties, including antioxidant, anticancer, anti-inflammatory, antimicrobial, antidiabetic, and antihyperlipidemic effects. Myricanol improves metabolic abnormalities in mice by activating the AMPK/SIRT1/PGC-1α signaling pathway. It also demonstrates significant anticancer, antioxidant, and anti-inflammatory actions, primarily by regulating Caspase and BCL-2 family proteins, inhibiting iNOS expression, scavenging free radicals, and interacting with Peroxiredoxin 5. Therefore, myricanol shows great potential for the treatment of cancer, metabolic abnormalities, and inflammatory bowel disease. Further research is needed to improve its bioavailability, confirm its pharmacological effects and mechanisms in vivo, and explore its pharmacokinetic properties and safety. Full article

Periodontitis (PD) and rheumatoid arthritis (RA) are chronic inflammatory disorders that impose substantial individual and societal burdens worldwide. PD is characterized by progressive destruction of the periodontal ligament and alveolar bone, leading to tooth loss, impaired oral function, and sustained systemic inflammatory burden. RA, affecting approximately 0.5–1% of the population, is a chronic autoimmune disease marked by persistent synovial inflammation, progressive joint destruction, disability, and reduced quality of life. Increasing evidence indicates that these conditions are biologically and clinically interconnected. Both diseases share key pathogenic pathways, including microbial dysbiosis, immune dysregulation, chronic inflammation, genetic susceptibility, and aberrant autoantibody responses. Particular attention has focused on keystone periodontal pathogens such as Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans, which may promote protein citrullination and the formation of anti-citrullinated protein antibodies (ACPA), thereby providing a plausible mechanistic bridge between periodontal infection and systemic autoimmunity. Shared genetic risk factors, including HLA-DRB1 susceptibility alleles, further support a common host predisposition. Clinical, epidemiological, and translational studies increasingly support a bidirectional association. Individuals with PD appear to have a higher risk of RA development, whereas patients with RA demonstrate greater prevalence, severity, and progression of periodontal disease. Interventional studies suggest that nonsurgical periodontal therapy may reduce local periodontal inflammation, circulating inflammatory biomarkers, and RA disease activity indices, while effective pharmacological control of RA may also improve periodontal outcomes. This narrative review critically evaluates the PD–RA relationship across four interconnected domains: (i) epidemiological and clinical associations between PD and RA, (ii) key mechanisms underlying RA pathogenesis, (iii) shared biological pathways linking both diseases, and (iv) the extent to which treatment of one condition influences the other. Particular emphasis is placed on major sources of heterogeneity and confounding—including smoking, metabolic comorbidities, disease stage, therapeutic exposure, and variable diagnostic definitions—that may explain inconsistencies across the literature. By integrating current mechanistic and clinical evidence, this review provides a structured synthesis that extends beyond a descriptive overview of association studies. A clearer understanding of the periodontal–rheumatologic axis may facilitate risk stratification, identify novel therapeutic targets, and support integrated multidisciplinary care. Targeting both oral and systemic inflammation may improve outcomes in patients with coexisting PD and RA and may potentially reduce the risk or severity of one condition in individuals already affected by the other. Full article

Background: Pulmonary arterial hypertension is a rare but life-threatening condition in children, with hereditary forms often being linked to mutations in genes such as bone morphogenetic protein receptor type 2 (BMPR2), caveolin 1 (CAV1), and potassium channel subfamily K member 3 (KCNK3). Among these, CAV1 mutations are associated with severe disease phenotypes, though cases resulting from de novo heterozygous CAV1 mutations with multi-system involvement remain rarely reported. The CAV1 mutation (c.424C > T, p.Q142X) disrupts caveolin-1 function, leading to dysregulated pulmonary vascular remodeling and multi-system abnormalities. Methods: This was a retrospective case study of a pediatric patient with hereditary PAH. The patient was followed at our hospital from initial presentation until death. Clinical data were collected from medical records, including physical examinations, laboratory tests, echocardiography, chest X-ray, computed tomography pulmonary angiography (CTPA), and genetic analysis. The patient was treated sequentially with various PAH-targeted medications. This report also includes a review of the relevant literature on CAV1-associated PAH. Results: A female aged 3 years and 11 months was diagnosed with hereditary PAH associated with a de novo heterozygous CAV1 mutation (c.424C > T, p.Q142X). Both parents underwent genetic testing and were negative for the mutation, confirming its de novo origin. Clinical manifestations included special facial features, congenital telangiectasia, cutis marmorata (marbled skin), congenital cataract, hereditary lipodystrophy, and severe PAH. The patient presented with progressive exercise intolerance, syncope, and worsening dyspnea over nine years. Echocardiography revealed pulmonary hypertension with an estimated pulmonary artery systolic pressure of 69–105 mmHg, right heart enlargement, right ventricular hypertrophy, and moderate tricuspid regurgitation. Blood and urine metabolic screenings were normal. A chest X-ray showed progressive enlargement of the cardiac silhouette and bulging of the pulmonary artery segment. CTPA demonstrated pulmonary hypertension, secondary right heart dysfunction, decompensated right ventricular function, and mosaic perfusion in both lungs, suggestive of small arterial branch occlusion. Right heart catheterization was declined by the parents. Thus, the diagnosis of PAH was established based on clinical, echocardiographic, CTPA, and genetic findings. The patient was hospitalized four times and lost to follow-up from 2017 to 2023. She received sequential treatment with digoxin, hydrochlorothiazide, tadalafil, ambrisentan, selexipag, and treprostinil. Despite these therapies, pulmonary artery pressure continued to rise with progressive clinical deterioration. The patient ultimately died at 13 years of age due to a pulmonary hypertensive crisis and multiple organ failure following a severe episode of gastroenteritis. Conclusions: Despite aggressive treatment with multiple targeted reduced pulmonary artery pressure drug therapies, managing hereditary PAH caused by CAV1 mutations in children remains a significant challenge, with a high mortality rate. Early genetic diagnosis, regular follow-up, and individualized treatment are crucial. It requires the joint efforts of patients, parents, and healthcare providers. Full article

Osteoporosis is a systemic skeletal disorder characterized by low bone mass, microarchitectural deterioration, and an increased risk of fracture. Its pathogenesis is closely associated with disturbances in energy metabolism, particularly glucose metabolic reprogramming in bone cells. Under osteoporotic conditions, the balance between osteoblasts and osteoclasts is disrupted, accompanied by impaired oxidative phosphorylation, dysregulated glycolysis, and reduced tricarboxylic acid cycle efficiency, ultimately leading to mitochondrial dysfunction. These metabolic alterations result in an insufficient energy supply and accelerate bone loss. Accordingly, the modulation of key enzymes involved in glucose metabolism has emerged as a promising therapeutic strategy. Strategies include the use of natural compounds, traditional Chinese medicine formulas, and specific inhibitors to modulate glucose metabolism processes and related pathways, thereby restoring cellular energy homeostasis and bone remodeling balance. This review summarizes pharmacological agents regulating glucose metabolism and proposes a hierarchical framework for therapeutic prioritization: first, inhibiting pathological glycolysis in osteoclasts (particularly via LDHA and PKM2). Second, restoring oxidative phosphorylation in osteoblasts (e.g., via COX I–V or ATP synthase). And third, employing multi-target traditional Chinese medicine formulas as complementary strategies. By establishing this cell-type-specific and pathway-specific hierarchy, the review aims to provide a theoretical basis for future research on metabolic interventions in bone diseases. Full article

Background: Chronic obstructive pulmonary disease (COPD) is associated with systemic alterations in body composition, including muscle mass loss and fat redistribution, which may influence patient-reported outcomes. However, the independent contribution of bioimpedance-derived parameters, particularly phase angle, to quality of life (QoL) remains unclear. Methods: This exploratory pilot study included 75 clinically stable patients with moderate-to-severe COPD (GOLD stages II–III). Body composition was assessed using segmental multi-frequency bioelectrical impedance analysis with the InBody 770 system. Evaluated parameters included fat-free mass (FFM), skeletal muscle mass (SMM), percent body fat (PBF), visceral fat area (VFA), extracellular water-to-total body water ratio (ECW/TBW), bone mineral content (BMC), and phase angle (PhA). Quality of life was assessed using the WHOQOL-BREF questionnaire. Associations between body composition parameters and QoL domains were analyzed using Spearman correlation analysis and multivariable linear regression models. Results: Despite a median body mass index (BMI) within the normal range (23.4 kg/m²), body fat mass exceeded reference values in both men and women. Fat-free mass and skeletal muscle mass were located near the lower range of expected values. Correlation analysis demonstrated predominantly weak associations between body composition parameters and QoL domains. Significant positive correlations were identified between the psychological QoL domain and fat-free mass (ρ = 0.238, p = 0.041), skeletal muscle mass (ρ = 0.240, p = 0.040), basal metabolic rate (ρ = 0.236, p = 0.043), and bone mineral content (ρ = 0.249, p = 0.033). In multivariable regression models, fat-free mass and skeletal muscle mass demonstrated consistent positive associations with both physical and psychological QoL domains. Whole-body and segmental phase angle parameters did not demonstrate significant associations with QoL outcomes. Conclusions: In patients with COPD, BMI alone may inadequately reflect underlying alterations in body composition. Muscle-related parameters, particularly fat-free mass and skeletal muscle mass, demonstrated more consistent associations with physical and psychological aspects of quality of life than obesity-related indicators. These findings suggest that bioelectrical impedance analysis may provide additional clinically relevant information beyond BMI when assessing body composition and quality of life in patients with COPD. Full article

Background/Objectives: Nutritional rickets is a childhood bone disorder leading to skeletal deformities and life-long disabilities. Early-stage diagnosis remains challenging due to the limited availability of non-invasive tools. This study explores metabolic variation associated with the active disease stages and with etiological factors, such as nutritional deficiencies and biochemical alterations. Methods: Untargeted ¹H NMR spectroscopy-based metabolomics were performed on urine and plasma samples collected from Bangladeshi children with radiologically active rickets (AR; n = 24; aged 2.98 ± 1.19 years), inactive rickets (IR; n = 36; aged 3.39 ± 1.87 years), and healthy matched controls (n = 58; aged 3.58 ± 1.59 years). This analysis also integrated corresponding clinical biochemistry and dietary intake data previously collected from the cohort. Results: Orthogonal Partial Least Squares-Discriminant Analysis (OPLS-DA) identified the 24 h urinary excretion of 13 metabolites to vary with AR, including those previously associated with bone metabolism such as β-aminoisobutyrate, N-methylnicotinamide, taurine and hypoxanthine. Biochemically, AR was strongly characterized by increased plasma alkaline phosphatase and decreased iFGF23. The multi-block integration of metabolomic, biochemical, and nutritional data achieved an 18.6% classification error rate. Children with IR exhibited metabolic profiles similar to healthy controls, aligning with their clinical resolution. Conclusions: Active nutritional rickets presents a distinct metabolic profile, highlighting novel biologically relevant metabolites. These exploratory signals provide insights into the physiological impact of the disease and warrant further targeted investigation to assess their potential for informing early non-invasive detection and preventive interventions. In the long term, such tools are vital to prevent irreversible skeletal damage and to help mitigate lifelong physical disability and the resulting social vulnerability for affected children. Full article

Chronic kidney disease–mineral and bone disorder (CKD-MBD) is a major complication of end-stage renal disease and is associated with increased morbidity and mortality. Sclerostin, an osteocyte-derived glycoprotein that inhibits the Wnt/β-catenin signaling pathway, has been implicated in the dysregulation of bone metabolism in dialysis patients. However, comparative data on sclerostin levels and their clinical determinants between hemodialysis (HD) and peritoneal dialysis (PD) patients remain limited, particularly in Southeast Asian populations. This cross-sectional study was conducted at Hue Central Hospital, Vietnam, between June 2023 and January 2026. A total of 89 end-stage renal disease patients were consecutively enrolled (HD: n = 51; PD: n = 38). Median serum sclerostin levels were 584.21 (IQR: 301.18–1479.50) pg/mL in the HD group and 684.21 (IQR: 407.48–940.35) pg/mL in the PD group, with no significant difference between groups (p = 0.839). Serum sclerostin was inversely correlated with PTH in both HD (r = −0.444, p = 0.001) and PD patients (r = −0.341, p = 0.036). In the HD group, total femur BMD showed a significant inverse correlation with sclerostin (r = −0.304, p = 0.030). In multivariable analysis, Log_PTH remained an independent predictor of sclerostin across all three sequential models in the HD group (Model 1: B = −0.340, p = 0.001; Model 2: B = −0.270, p = 0.035; Model 3: B = −0.268, p = 0.039; adjusted R² range: 0.197–0.217) and in the combined HD + PD cohort (Model 1: B = −0.271, p < 0.001; Model 2: B = −0.263, p < 0.001; Model 3: B = −0.249, p = 0.003; adjusted R² range: 0.141–0.158). In the PD subgroup, Log_PTH was significant in Models 1 and 2 but not in Model 3; none of the models reached overall statistical significance (all p ≥ 0.081), and findings should be considered exploratory given the limited sample size. Serum sclerostin levels did not differ significantly between HD and PD patients. PTH was the most consistent independent predictor of sclerostin across dialysis modalities and analytical models, underscoring its central role in CKD-MBD pathophysiology. Larger prospective multicenter studies are warranted to validate these findings and further clarify the clinical utility of sclerostin in dialysis populations. Full article

Multiple myeloma profoundly remodels the bone marrow microenvironment, causing osteolytic bone disease through a persistent uncoupling of bone resorption and formation. Beyond the canonical roles of the receptor activator of nuclear factor kappa-B ligand/receptor activator of nuclear factor kappa-B/osteoprotegerin triad and Wnt antagonism, three interdependent stress programs orchestrate the osteolytic niche. These include oxidative stress driven by mitochondrial and nicotinamide adenine dinucleotide phosphate oxidase-derived reactive oxygen species; sterile inflammation sustained by damage-associated molecular patterns, pattern-recognition receptors, and pro-inflammatory cytokines; and autophagy–lysosomal remodeling governed by transcription factor EB and the coordinated lysosomal expression and regulation network. These axes intersect with iron handling and lipid peroxidation to regulate sensitivity to ferroptotic cell death, thereby shaping osteoclast priming, osteoblast suppression, and matrix turnover. Building on these mechanistic insights, we outline a translational framework that aligns standardized bone turnover markers of formation and resorption with composite panels of oxidative and nitrosative stress. This framework also integrates modern imaging to capture structural injury and metabolically active marrow disease. We further propose a therapeutic roadmap layered on antiresorptive foundations that targets selective inhibition of nicotinamide adenine dinucleotide phosphate oxidase 4 and calibrated modulation of nuclear factor erythroid 2–related factor 2, disrupts damage-associated molecular pattern and cytokine circuits, and applies lineage- and timing-specific tuning of autophagy together with restoration of ferroportin-1 or iron chelation. This integrated strategy is designed to recouple bone remodeling and improve clinically meaningful skeletal outcomes in multiple myeloma. Full article

Background: Antihyperlipidemic medications are widely prescribed for the management of dyslipidemia and prevention of cardiovascular disease and may also influence bone metabolism, formation, and repair. However, their impact on peri-implant bone remodeling and dental implant survival remains insufficiently investigated. Objectives: The aim of this study was to evaluate the influence of antihyperlipidemic therapy on dental implant survival and failure rates over a ten-year period. Methods: A retrospective cohort study included 552 patients receiving 1680 dental implants between 2012 and 2022. Patients were divided into a control group (512 patients; 1581 implants) and a study group receiving antihyperlipidemic monotherapy (40 patients; 99 implants). Clinical, radiographic, and demographic data were collected and analyzed, and implant failure was assessed according to the established clinical criteria of the International Congress of Oral Implantologists. Results: Kaplan–Meier analysis demonstrated significantly better dental implant survival in patients receiving antihyperlipidemic therapy (log-rank p = 0.046). The failure rate was lower in the study group (1.01%) compared with the control group (5.12%). Cox regression analysis, adjusted for age, sex, implant diameter and length, insertion torque, and bone quality, showed that antihyperlipidemic therapy was associated with a markedly reduced risk of implant failure (HR = 0.16). Overall, the use of antihyperlipidemic medications was associated with a significantly lower risk of implant failure (p < 0.05), suggesting a beneficial effect on long-term dental implant survival. Conclusions: The present findings indicate that antihyperlipidemic therapy may be associated with improved dental implant survival and enhanced osseointegration. These results should be interpreted as hypothesis-generating and necessitate confirmation in future prospective randomized controlled studies with expanded and more balanced cohorts. Full article

Periodontitis is a chronic inflammatory disease which is initiated by dysbiotic biofilms and maintained by a host who is permissive to inflammation resulting in continuous destruction of periodontal supporting structures. Periodontitis occurs frequently with obesity and type 2 diabetes mellitus and the broader cardiometabolic risk state leading to investigations into the common immunometabolic pathways that link these conditions. Adiponectin, an insulin sensitizing and anti-inflammatory adipokine which can also act as a vasculoprotective and bone-related factor, has been studied as a potential modulator of the relation between periodontal inflammation and systemic metabolic disturbance. This narrative review summarizes the biology of adiponectin and its receptors, human findings relating to both the local and circulating forms of adiponectin in periodontal health and disease, the mechanism in cell and animal models and translational implications and limitations. The literature was reviewed in a narrative manner with particular attention to study quality, compartment-specific biology and any conflicts in evidence and the difference between biological plausibility and clinical relevance. A tendency for a reduction in the circulating, saliva and gingival crevicular fluid levels of adiponectin in periodontitis in human studies, particularly those with co-existing obesity and type 2 diabetes mellitus, can be demonstrated but these finding are often disparate due to variable methods in case definitions, assay techniques, metabolic background of subjects and other confounders. Experimental findings may establish biological plausibility by linking adiponectin signalling with the mechanisms which affect inflammatory responses, endothelial function and matrix homeostasis, osteoclastogenesis and subsequent alveolar bone loss, although adiponectin signalling appears context-specific in its actions and this does not confirm clinical relevance. Evidence suggests adiponectin is a biologically significant, but context-dependent factor within the immunometabolic network which connects periodontal disease with the systemic condition, rather than a sole marker or clinically recognized target for therapeutic intervention. Full article

Combined immune checkpoint inhibition (ICI) and multitargeted tyrosine kinase inhibition (TKI) improve outcomes in advanced melanoma, especially in heavily pretreated patients, but introduce complex, overlapping toxicities. Although immune-related adverse events and TKI-specific toxicities are well characterized individually, their concurrent presentation is uncommon and can obscure diagnosis. Capillary leak syndrome (CLS), a rare but potentially life-threatening complication of ICIs, further complicates recognition due to nonspecific features and variable onset. A 43-year-old woman with metastatic BRAF wild-type melanoma, in complete metabolic response on lenvatinib and pembrolizumab, presented with generalized edema, hypotension, thrombocytopenia, and marked erythroblastosis. Extensive evaluation, including bone marrow analysis, excluded malignancy, infection, and autoimmune disease, but revealed multilineage dysplasia with pronounced erythroid stress. Imaging confirmed sustained remission with pleural effusions and ascites. Dual toxicity was suspected: lenvatinib-related hematologic toxicity and pembrolizumab-associated CLS. Both agents were discontinued, and corticosteroids followed by IVIG for steroid-refractory edema led to gradual recovery. This case underscores the diagnostic challenge of overlapping ICI–TKI toxicities. Mechanistically, VEGF pathway inhibition may disrupt marrow endothelial integrity and hematopoietic homeostasis, promoting cytopenias and erythroid precursor release, while immune activation drives cytokine-mediated endothelial dysfunction and vascular hyperpermeability. Early recognition and prompt immunomodulatory management are critical to improving outcomes. Full article

Bone metastasis remains a major cause of morbidity in advanced cancer, driven not only by tumor–bone crosstalk but also by profound immune remodeling within the marrow. Myeloid-derived suppressor cells (MDSCs), including polymorphonuclear (PMN-MDSC) and monocytic (M-MDSC) subsets, are increasingly recognized as central effectors of this process, integrating inflammatory signals with metabolic and stromal cues to enforce immune suppression and support skeletal colonization. In this review, we synthesize current evidence that bone metastases transform the bone marrow into an “MDSC amplifier,” where vascular and endosteal niches, CXCL12-rich stromal compartments, hypoxia, and adipocyte-derived lipids collectively promote MDSC recruitment, persistence, and functional maturation. We discuss the dominant suppressive programs deployed by MDSCs in bone (e.g., arginase-1 activity, reactive oxygen/nitrogen species, and checkpoint ligand expression), and how these mechanisms converge to impair cytotoxic T-cell and NK-cell responses while fostering regulatory T-cell dominance. Importantly, because the marrow is a hematopoietic organ, bone lesions can also generate systemic consequences through myeloid spillover, providing a mechanistic basis for reduced responsiveness to immune checkpoint blockade in bone-dominant disease. We then evaluate pharmacologic strategies to target MDSCs in the context of bone metastasis, including approaches that block trafficking (e.g., CCR2/CXCR2 axes), deplete or reprogram suppressive myeloid states (e.g., STAT3-directed strategies, differentiation therapy), and disrupt bone-resorptive feedback loops (e.g., receptor activator of NF-κB ligand (RANKL) inhibition and bisphosphonates), emphasizing rational combinations and sequencing to limit marrow toxicity. Finally, we highlight emerging single-cell and spatial profiling tools that can resolve bone-specific heterogeneity in MDSCs and guide biomarker-driven, mechanism-informed therapeutic development. Full article

Background: Thyroid hormones influence bone metabolism, and autoimmune thyroid diseases may further impact skeletal homeostasis. Wnt signaling inhibitors, including Dickkopf-1 (DKK-1) and sclerostin (SOST), as well as osteoprotegerin (OPG), play key roles in regulating bone formation and resorption. This study aimed to evaluate circulating DKK-1, SOST, and OPG in women with newly diagnosed overt thyroid dysfunction. Methods: This cross-sectional study included 62 women with newly diagnosed, untreated overt thyroid dysfunction (35 hypothyroid and 27 hyperthyroid) and 33 age- and BMI-matched healthy controls. Serum levels of DKK-1, sclerostin, and OPG were measured using ELISA. Thyroid function and autoantibodies were assessed using automated immunoassays. Correlation analysis was performed to evaluate associations between variables. Results: Serum DKK-1 levels were significantly elevated in both hypothyroid and hyperthyroid women compared with controls (p < 0.001). Sclerostin levels showed a non-significant trend toward higher values. OPG levels were significantly increased in hyperthyroid patients and moderately elevated in hypothyroid patients. Significant positive correlations were observed between OPG and FT3 (r = 0.42, p = 0.001) and FT4 (r = 0.43, p = 0.001). In hypothyroid patients, OPG correlated positively with TgAb (r = 0.46, p = 0.007). A strong positive correlation was found between DKK-1 and SOST (p < 0.001), while DKK-1 was negatively associated with age (p < 0.05). Conclusions: Overt thyroid dysfunction is associated with significant alterations in circulating Wnt signaling inhibitors and OPG. These findings suggest a potential role of Wnt signaling and immune–bone interactions in thyroid-related changes in bone metabolism. Full article

Heart failure (HF) has traditionally been regarded as a primary myocardial disorder in veterinary medicine. However, accumulating evidence suggests that HF represents a systemic syndrome characterized by dynamic multiorgan interactions. In human cardiovascular research, cardiorenal and cardiointestinal paradigms have reshaped disease conceptualization, yet comparable integrative frameworks remain underdeveloped in veterinary cardiology. Naturally occurring canine HF—particularly myxomatous mitral valve disease and dilated cardiomyopathy—offers a clinically relevant translational platform in which systemic remodeling unfolds within an intact physiological lifespan. This review proposes a systems-based perspective that integrates spontaneous canine HF with controlled in vivo experimental models. We outline four main pathways of interaction: (1) the heart–gut axis, wherein reduced perfusion can influence inflammation and disruption of the intestinal barrier; (2) the heart–bone axis, wherein endocrine factors like osteoprotegerin and osteocrin can impact remodeling of the cardiovascular system; (3) the heart–vascular endothelium axis, wherein inflammatory signaling and dysfunction of the vascular endothelium are hallmarks; and (4) the neurocardiac axis, which reflects an imbalance in the autonomic nervous system. Emerging regenerative and organelle-based strategies—including mesenchymal stem cell therapy and mitochondrial transplantation—are discussed within this multiorgan framework. Rather than focusing solely on cardiac contractility, these approaches may function as systemic inflammatory modulators, and endothelial, metabolic, and autonomic pathways. Canine HF can be better understood as a multiorgan network condition; reframing it in this way can help researchers in the field of translational cardiology create more comprehensive diagnostic and treatment plans. Full article