Search Results (10,457)

Hypertension (HTN) is a major contributor to global morbidity and manifests in several variants, including salt-sensitive hypertension (SSHTN). SSHTN is defined by an increase in blood pressure (BP) in response to high dietary salt, and is associated with heightened cardiovascular risk, renal damage, and immune system activation. However, the role of granulocyte-macrophage colony-stimulating factor (GM-CSF) has not yet been explored in the context of SSHTN. Previously, we reported that GM-CSF is critical in priming bone marrow-derived (BMD)-macrophages (BMD-Macs) and BMD-dendritic cells (BMD-DCs) to become activated (CD38+) in response to salt. Further exploration revealed these cells differentiated into BMD-M1 Macs, CD38+ BMD-M1 Macs, BMD-type-2 conventional DCs (cDC2s), and CD38+ BMD-cDC2s. Additionally, BMD-monocytes (BMDMs) grown with GM-CSF and injected into SSHTN mice traffic to the kidneys and differentiate into Macs, CD38+ Macs, DCs, and CD38+ DCs. In the current study, we treated SSHTN mice with an anti-GM-CSF antibody (aGM) and found that preventive aGM treatment mitigated BP, prevented renal inflammation, and altered renal immune cells. In mice with established SSHTN, aGM treatment attenuated BP, reduced renal inflammation, and differentially affected renal immune cells. Adoptive transfer of aGM-treated BMDMs into SSHTN mice resulted in decreased renal trafficking. Additionally, aGM treatment of BMD-Macs, CD38+ BMD-M1 Macs, BMD-DCs, and CD38+ BMD-cDC2s led to decreased pro-inflammatory gene expression. These findings suggest that GM-CSF plays a role in SSHTN and may serve as a potential therapeutic target. Full article

Chronic Obstructive Pulmonary Disease (COPD) is a multifactorial condition associated with significant systemic complications such as cardiovascular disease (CVD), metabolic disorders, muscle wasting, and sarcopenia. While Body Mass Index (BMI) is a well-established indicator of obesity and has prognostic value in COPD, its role in predicting disease outcomes is complex. Muscle wasting is prevalent in COPD patients and exacerbates disease severity, contributing to poor physical performance, reduced quality of life, and increased mortality. Additionally, COPD is linked to metabolic disorders, such as dyslipidemia and diabetes, which contribute to systemic inflammation and worse prognosis and, therefore, should be treated. The systemic inflammatory response plays a central role in the development of sarcopenia. In this review, we highlight the mixed efficacy of statins in managing dyslipidemia in COPD, considering side effects, including muscle toxicity in such a frail population. Alternative lipid-lowering therapies and nutraceuticals, in addition to standard treatment, have the potential to target hypercholesterolemia, which is a coexisting condition present in more than 50% of all COPD patients, without worsening muscle wasting. The interference between adipose tissue and lung, and particularly the potential protective role of adiponectin, an adipocytokine with anti-inflammatory properties, is also reviewed. Respiratory, metabolic and muscular health in COPD is comprehensively assessed. Identifying and managing dyslipidemia and paying attention to other relevant COPD comorbidities, such as sarcopenia and muscle wasting, is important to improve the quality of life and to reduce the clinical burden of COPD patients. Future research should focus on understanding the relationships between these intimate mechanisms to facilitate specific treatment for systemic involvement of COPD. Full article

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic upper airway disease that may involve different inflammatory endotypes, although in Western populations it is most commonly associated with type 2 inflammation. CRSwNP has a significant impact on the patient’s quality of life. The recommended appropriate medical therapy is effective in controlling CRSwNP symptoms in many patients; however, a subset continues to exhibit persistent type 2 inflammation, evidenced by recurrent nasal polyps, elevated eosinophil counts, or the need for systemic corticosteroids or surgery. Monoclonal antibodies have recently become a novel and personalized treatment that can help refractory patients restore disease control. Objective: The present study aims to evaluate the effectiveness of mepolizumab in real-world settings in a diverse patient population, focusing on assessing the impact of this therapy on patient-reported outcomes after six months of treatment. Methods: This is a multicenter, observational study of CRSwNP patients treated with mepolizumab carried out in five hospitals located in Spain. Adult patients with a diagnosis of uncontrolled CRSwNP were included in the study. The change in the nasal polyp score (NPS) was the main clinical endpoint. Changes in the Sinonasal Outcome Test (SNOT-22), nasal congestion and smell impairment visual analogue scale scores, and blood and nasal polyp tissue eosinophil counts were among other endpoints included. Results: In total, 47 patients were included, and 91% were asthmatic. The nasal polyp score (0–8) was reduced significantly in the cohort (mean change: −2.56, p < 0.0001). The mean SNOT-22 score improved 25.29 points. Nasal congestion (−3.57, p < 0.0001) and smell impairment (−4.0, p < 0.0001) visual analog scale scores (0–10) showed a significant improvement. Blood and tissue eosinophil median counts showed significant reductions versus baseline of 86% and 26%, respectively. Among those patients with asthma, the asthma control test score achieved a median value of 24 points. Conclusions: This study provides real-world evidence supporting the effectiveness of mepolizumab in managing CRSwNP in patients with features suggestive of type 2 inflammation. The observed improvements in patient-reported outcomes, nasal polyp burden, and asthma control suggest that mepolizumab may be a valuable therapeutic option for this patient population. Full article

Kidney transplant recipients face a substantial burden of premature mortality and morbidity, primarily due to persistent inflammation, cardiovascular risk, and nutritional deficiencies. Traditional nutritional interventions in this population have either focused on supplementing individual nutrients—often with limited efficacy—or required comprehensive dietary overhauls that compromise patient adherence. In this narrative review, we explore the rationale for dietary nut enrichment as a feasible, multi-nutrient strategy tailored to the needs of kidney transplant recipients. Nuts, including peanuts and tree nuts with no added salt, sugar, or oil, are rich in beneficial fats, proteins, vitamins, minerals, and bioactive compounds. We summarize the multiple post-transplant challenges—including obesity, sarcopenia, dyslipidemia, hypertension, immunological dysfunction, and chronic inflammation—and discuss how nut consumption may mitigate these issues through mechanisms involving improved micro-nutrient intake (e.g., magnesium, potassium, selenium), lipid profile modulation, endothelial function, immune support, and gut microbiota health. Additionally, we highlight the scarcity of randomized controlled trials in high-risk populations such as kidney transplant recipients and make the case for studying this group as a model for investigating the clinical efficacy of nuts as a nutritional intervention. We also consider practical aspects for future clinical trials, including the choice of study population, intervention design, duration, nut type, dosage, and primary outcome measures such as systemic inflammation. Finally, potential risks such as nut allergies and oxalate or mycotoxin exposure are addressed. Altogether, this review proposes dietary nut enrichment as a promising, simple, and sustainable multi-nutrient approach to support cardiometabolic and immune health in kidney transplant recipients, warranting formal investigation in clinical trials. Full article

Background: Toxoplasma gondii (T. gondii) causes severe disease in immunocompromised individuals and pregnant women, underscoring the urgent need for effective vaccines against toxoplasmosis. The dense granule protein 5 (GRA5) of T. gondii plays a key role in parasitic cyst formation. Methods: This study evaluated the protective immune responses induced by a virus-like particle (VLP) vaccine expressing the T. gondii-derived antigen GRA5 in a mouse model challenged with the ME49 strain of T. gondii. GRA5 VLPs were generated using a baculovirus expression system, and VLP formation was confirmed by Western blotting and visualized using transmission electron microscopy. Mice were intranasally immunized with GRA5 VLPs three times at 4-week intervals to induce immune responses, followed by infection with T. gondii ME49. Results: Intranasal immunization with GRA5 VLPs induced parasite-specific IgG antibody responses in the serum and both IgG and IgA antibody responses in the brain. Compared to the non-immunized group, immunized mice exhibited significantly higher levels of germinal center B cells and antibody-secreting cell responses. Moreover, the VLP vaccine suppressed the production of IFN-γ and IL-6 cytokines, leading to a significant reduction in brain inflammation and decreased cyst counts following lethal challenge with T. gondii ME49 infection. Conclusion: These findings suggest that the GRA5 VLP vaccine derived from T. gondii elicits a protective immune response, highlighting its potential as an effective vaccine candidate against toxoplasmosis. Full article

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing lung disease characterized by chronic inflammation, vascular remodeling, and immune dysregulation. COVID-19, caused by SARS-CoV-2, shares several systemic immunohematologic disturbances with IPF, including cytokine storms, endothelial injury, and prothrombotic states. Unlike general comparisons of viral infections and chronic lung disease, this review offers a focused analysis of the shared hematologic and immunologic mechanisms between COVID-19 and IPF. Our aim is to better understand how SARS-CoV-2 infection may worsen disease progression in IPF and identify converging pathophysiological pathways that may inform clinical management. We conducted a narrative synthesis of the peer-reviewed literature from PubMed, Scopus, and Web of Science, focusing on clinical, experimental, and pathological studies addressing immune and coagulation abnormalities in both COVID-19 and IPF. Both diseases exhibit significant overlap in inflammatory and fibrotic signaling, particularly via the TGF-β, IL-6, and TNF-α pathways. COVID-19 amplifies coagulation disturbances and endothelial dysfunction already present in IPF, promoting microvascular thrombosis and acute exacerbations. Myeloid cell overactivation, impaired lymphocyte responses, and fibroblast proliferation are central to this shared pathophysiology. These synergistic mechanisms may accelerate fibrosis and increase mortality risk in IPF patients infected with SARS-CoV-2. This review proposes an integrative framework for understanding the hematologic and immunologic convergence of COVID-19 and IPF. Such insights are essential for refining therapeutic targets, improving prognostic stratification, and guiding early interventions in this high-risk population. Full article

Background and Objectives: Coronavirus Disease 2019 (COVID-19) may cause extensive multi-organ pathology, particularly in the lungs, heart, kidneys, and liver. While hypercoagulability—often signaled by elevated D-dimer—has been thoroughly investigated, the concurrent pathological findings across organs and their interrelation with distinct D-dimer levels remain incompletely characterized. This study aimed to evaluate the pathological changes observed in autopsied or deceased COVID-19 patients, focusing on the prevalence of organ-specific lesions, and to perform subgroup analyses based on three D-dimer categories. Methods: We conducted a retrospective review of 69 COVID-19 patients from a Romanian-language dataset, translating all clinical and pathological descriptions into English. Pathological findings (pulmonary microthrombi, bronchopneumonia, myocardial fibrosis, hepatic steatosis, and renal tubular necrosis) were cataloged. Patients were grouped into three categories by admission D-dimer: <500 ng/mL, 500–2000 ng/mL, and ≥2000 ng/mL. Laboratory parameters (C-reactive protein, fibrinogen, and erythrocyte sedimentation rate) and clinical outcomes (intensive care unit [ICU] admission, mechanical ventilation, and mortality) were also recorded. Intergroup comparisons were performed with chi-square tests for categorical data and one-way ANOVA or the Kruskal–Wallis test for continuous data. Results: Marked organ pathology was significantly more frequent in the highest D-dimer group (≥2000 ng/mL). Pulmonary microthrombi and bronchopneumonia increased stepwise across ascending D-dimer strata (p < 0.05). Myocardial and renal lesions similarly showed higher prevalence in patients with elevated D-dimer. Correlation analysis revealed that severe lung and heart pathologies were strongly associated with high inflammatory markers and a greater risk of ICU admission and mortality. Conclusions: Our findings underscore that COVID-19-related organ damage is magnified in patients with significantly elevated D-dimer. By integrating pathology reports with clinical and laboratory data, we highlight the prognostic role of hypercoagulability and systemic inflammation in the pathogenesis of multi-organ complications. Stratifying patients by D-dimer may inform more tailored management strategies, particularly in those at highest risk of severe pathology and adverse clinical outcomes. Full article

Background: Chronic cytomegalovirus (CMV) infection may favor the development of immunosenescence and inflammation that impair vaccine responses, including COVID-19. In addition, the polymorphism of the interferon-lambda gene (IFNλ) affects COVID-19 immune responses in older adults. Objective: We aimed to investigate the impact of IFNλ polymorphism (IL28B gene-rs12979860) on the immune/inflammatory response to vaccination with CoronaVac for COVID-19 in older adults who were CMV-seropositive. Methods: Blood samples from 42 CMV-seropositive older adults (73.7 ± 4.5 years) were collected before and 30 days after immunization with a second dose of the CoronaVac vaccine to evaluate the immune/inflammatory response. Results: At genotyping, 20 subjects were homozygous for the C/C alleles (Allele-1 group), 5 were homozygous for the T/T Alleles (Allele-2 group), and 17 were heterozygous (C/T, Alleles-1/2 group). The Allele-1 group showed higher IgG levels for COVID-19 (p = 0.0269) and intermediate monocyte percentage (p = 0.017), in contrast to a lower non-classical monocyte percentage (p = 0.0141) post-vaccination than pre-vaccination. Also, this group showed that IgG levels for CMV were positively associated with a systemic pro-inflammatory state and senescent T cells (CD4+ and CD8+). The Allele-2 group presented higher IFN-β levels at pre- (p = 0.0248) and post-vaccination (p = 0.0206) than the values in the Allele-1 and Alleles-1/2 groups, respectively. In addition, the Allele-2 and Alleles-1/2 groups showed that IgG levels for COVID-19 were positively associated with a balanced systemic inflammatory state. Conclusion: CMV-seropositivity in older adults who had Allele-1 could lead to an unbalanced systemic inflammatory state, which may impair their antibody response to COVID-19 vaccination compared to other volunteer groups. Full article

Inflammatory bowel disease (IBD), a heterogeneous group of recurring inflammatory conditions of the digestive system that encompass both ulcerative colitis (UC) and Crohn’s disease (CD), pose a significant public health challenge, currently lacking a definitive cure. The specific etiopathogenesis of IBD is not yet fully understood, but a multifactorial interplay of genetic and environmental factors is suspected. A growing body of evidence supports the involvement of intestinal dysbiosis in the development of IBD, including the effects of dysbiosis on the integrity of the intestinal epithelial barrier, modulation of the host immune system, alterations in the enteric nervous system, and the perpetuation of chronic inflammation. A comprehensive understanding of these mechanisms is important to define preventive measures, to develop new effective and lasting treatments, and to improve disease outcome. This review examines the complex tri-directional relationship between gut microbiota, mucosal immune system, and intestinal epithelium in IBD. In addition, nonpharmacological and behavioral strategies aimed at restoring a proper microbial–immune relationship will be suggested. Full article

Background: Halitosis is a common condition often rooted in periodontal disease and exacerbated by systemic disorders such as obesity. This short-term clinical evaluation investigates the relationship between halitosis, obesity, and periodontitis, and assesses the efficacy of a natural essential oil mouthwash as an adjunctive oral hygiene intervention. Methods: In this randomized, placebo-controlled clinical trial, 45 obese patients with diagnosed periodontitis and self-reported halitosis were randomly assigned to either a test group (n = 30), receiving an essential oil-based mouthwash, or a control group (n = 15), receiving a placebo. Over 28 days, participants were evaluated using plaque index (PI), bleeding on probing (BOP), organoleptic scoring, and BANA test results. Both subjective and objective halitosis assessments were performed. Results: The test group showed marked improvements in all parameters compared to controls. PI decreased by 31.5% in the test group versus 9.25% in controls; BOP reduced by 34.5% versus 6.0%; BANA test positivity dropped by 38.1% in the test group. Organoleptic scores improved by 45.9% (examiner-rated) and 36.8% (self-assessed) in the test group. Conclusions: This 28-day clinical evaluation demonstrates the potential of an essential oil-based mouthwash to significantly reduce halitosis and periodontal inflammation in obese individuals with periodontitis. The necessity of future randomized trials is evident to substantiate the sustained benefits and safety of the intervention. Full article

Traditionally studied in isolation, the oral and gut microbiota are now being recognized as interconnected through anatomical and physiological pathways forming a dynamic “oral–gut microbiota axis”. Both oral and gut microbiota undergo changes with aging, characterized by a decline in microbial diversity and a shift toward potentially harmful species. The aim of this review is, therefore, to provide an overview of oral–gut communications in mediating frailty and sarcopenia. PubMed, EMBASE and Scopus databases were searched for relevant articles. We limited our search to manuscripts published in the English language. Interactions between oral and gut microbiota occur mainly through three pathways namely the enteral, the bloodstream and the fecal-oral routes. Alterations in the oral–gut microbiota axis contribute to chronic low-grade inflammation (i.e., “inflamm-ageing”) and mitochondrial dysfunction, key mechanisms underlying frailty and sarcopenia. Microbial metabolites, such as short-chain fatty acids and modified bile acids, appear to play an emerging role in influencing microbial homeostasis and muscle metabolism. Furthermore, poor oral health associated with microbial dysbiosis may contribute to altered eating patterns that negatively impact gut microbiota eubiosis, further exacerbating muscle decline and the degree of frailty. Strategies aimed at modulating the microbiota, such as healthy dietary patterns with reduced consumption of ultra-processed foods, refined carbohydrates and alcohol, ensuring an adequate protein intake combined with physical exercise, as well as supplementation with prebiotics, probiotics, and omega-3 polyunsaturated fatty acids, are increasingly recognized as promising interventions to improve both oral and gut microbiota health, with beneficial effects on frailty and sarcopenia. A better understanding of the oral–gut microbiota axis offers promising insights into nutritional interventions and therapeutic strategies for the age-related muscle decline, frailty and systemic health maintenance. Full article

Background/Objectives: Ultraviolet B (UVB) radiation contributes significantly to skin aging and skin disorders by promoting oxidative stress, inflammation, and collagen degradation. Natural antioxidants such as theaflavins and thearubigins from Camellia sinensis L. (black tea) have shown photoprotective effects. This study aimed to optimize the extraction of theaflavins and thearubigins from black tea leaves and evaluate the efficacy of the extract against UVB-induced damage using a transfersome-based topical formulation. Methods: Extraction of theaflavins and thearubigins was optimized via response surface methodology (Box-Behnken Design), yielding an extract rich in active polyphenols. This extract was incorporated into transfersomes that were characterized for size, polydispersity, zeta potential, storage stability, and entrapment efficiency. Human dermal fibroblasts (NHDF) were used to assess cytotoxicity, protection against UVB-induced viability loss, collagen degradation, and expression of inflammatory (IL6, COX2, iNOS) and matrix-degrading (MMP1) markers. Cellular uptake of the extract’s bioactive marker compounds was measured via LC-MS/MS. Results: The transfersomes (~60 nm) showed a good stability and a high entrapment efficiency (>85%). The transfersomes significantly protected NHDF cells from UVB-induced cytotoxicity, restored collagen production, and reduced gene expression of MMP1, IL6, COX2, and iNOS. Cellular uptake of key extract’s polyphenols was markedly enhanced by the nanoformulation compared to the free extract. Conclusions: Black tea extract transfersomes effectively prevented UVB-induced oxidative and inflammatory damage in skin fibroblasts. This delivery system enhanced bioavailability of the extract and cellular protection, supporting the use of the optimized extract in cosmeceutical formulations targeting photoaging and UV-induced skin disorders. Full article

Objectives: Saffron, a traditional Chinese medicine, is renowned for its pharmacological effects in promoting blood circulation, resolving blood stasis, regulating menstruation, detoxification, and alleviating mental disturbances. Trans-crocetin, its principal bioactive component, exhibits significant anti-hypoxic activity. The clinical development and therapeutic efficacy of trans-crocetin are limited by its instability, poor solubility, and low bioavailability. Conversion of trans-crocetin into trans-sodium crocetinate (TSC) enhances its solubility, stability, and bioavailability, thereby amplifying its anti-hypoxic potential. Methods: This study integrates network pharmacology with in vivo and in vitro validation to elucidate the molecular targets and mechanisms underlying TSC’s therapeutic effects against high-altitude acute lung injury (HALI), aiming to identify novel treatment strategies. Results: TSC effectively reversed hypoxia-induced biochemical abnormalities, ameliorated lung histopathological damage, and suppressed systemic inflammation and oxidative stress in HALI rats. In vitro, TSC mitigated CoCl₂-induced hypoxia injury in human pulmonary microvascular endothelial cells (HPMECs) by reducing inflammatory cytokines, oxidative stress, and ROS accumulation while restoring mitochondrial membrane potential. Network pharmacology and pathway analysis revealed that TSC primarily targets the EGFR/PI3K/AKT/NF-κB signaling axis. Molecular docking and dynamics simulations demonstrated stable binding interactions between TSC and key components of this pathway. ELISA and RT-qPCR confirmed that TSC significantly downregulated the expression of EGFR, PI3K, AKT, NF-κB, and their associated mRNAs. Conclusions: TSC alleviates high-altitude hypoxia-induced lung injury by inhibiting the EGFR/PI3K/AKT/NF-κB signaling pathway, thereby attenuating inflammatory responses, oxidative stress, and restoring mitochondrial function. These findings highlight TSC as a promising therapeutic agent for HALI. Full article

Autoimmune diseases such as systemic lupus erythematosus and Sjögren’s syndrome show pronounced sex disparities in prevalence, severity, and clinical outcomes, with females disproportionately affected. Emerging evidence highlights sex-based differences in immune and inflammatory responses as key contributors to this bias. Genetic factors—including sex chromosomes, skewed X chromosome inactivation, and sex-biased microRNAs—as well as sex hormones and pregnancy modulate gene expression and immune cell function in a sex-specific manner. Additionally, sex hormone-dependent epigenetic modifications influence the transcription of critical immune regulators. These genetic and hormonal factors collectively shape the activation, differentiation, and effector functions of diverse immune cell types. Environmental factors—including infections, gut microbiota, environmental chemicals and pollutants, and lifestyle behaviors such as diet, smoking, UV exposure, alcohol and caffeine intake, physical activity, and circadian rhythms—further modulate immune function and autoimmune disease pathogenesis in a sex-dependent manner. Together, these mechanisms contribute to the heightened risk and distinct clinical features of autoimmunity in females. A deeper understanding of sex-biased immune regulation will facilitate the identification of novel biomarkers, enable patient stratification, and inform the development of sex-specific diagnostic and therapeutic strategies for autoimmune diseases. Full article

Inflammatory Bowel Disease (IBD), which includes ulcerative colitis (UC) and Crohn’s disease (CD), results from dysregulated immune responses that drive chronic intestinal inflammation. Neutrophils, as key effectors of the innate immune system, contribute to IBD through multiple mechanisms, including the release of reactive oxygen species (ROS), pro-inflammatory cytokines, and neutrophil extracellular traps (NETs). NETs are web-like structures composed of DNA, histones, and associated proteins including proteolytic enzymes and antimicrobial peptides. NET formation is increased in IBD and has a context-dependent role; under controlled conditions, NETs support antimicrobial defense and tissue repair, whereas excessive or dysregulated NETosis contributes to epithelial injury, barrier disruption, microbial imbalance, and thrombotic risk. This review examines the roles of neutrophils and NETs in IBD. We summarize recent single-cell and spatial-omics studies that reveal extensive neutrophil heterogeneity in the inflamed gut. We then address the dual role of neutrophils in promoting tissue damage—through cytokine release, immune cell recruitment, ROS production, and NET formation—and in supporting microbial clearance and mucosal healing. We also analyze the molecular mechanisms regulating NETosis, as well as the pathways involved in NET degradation and clearance. Focus is given to the ways in which NETs disrupt the epithelial barrier, remodel the extracellular matrix, contribute to thrombosis, and influence the gut microbiota. Finally, we discuss emerging therapeutic strategies aimed at restoring NET homeostasis—such as PAD4 inhibitors, NADPH oxidase and ROS pathway modulators, and DNase I—while emphasizing the need to preserve antimicrobial host defenses. Understanding neutrophil heterogeneity and NET-related functions may facilitate the development of new therapies and biomarkers for IBD, requiring improved detection tools and integrated multi-omics and clinical data. Full article