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Project description:Alcohol-associated liver disease (ALD) is a major health problem with limited effective treatment options. Alcohol-associated hepatitis (AH) is a subset of severe ALD with a high rate of mortality due to infection, severe inflammation, and ultimately multi-organ failure. There is an urgent need for novel therapeutic approaches to alleviate the human suffering associated with this condition. Resolvin D1 (RvD1) promotes the resolution of inflammation and regulates immune responses. The current study aimed to test the therapeutic efficacy and mechanisms of RvD1-mediated effects on liver injury and inflammation in an experimental animal model that mimics severe AH in humans. Our data demonstrated that mice treated with RvD1 had attenuated liver injury and inflammation caused by EtOH and LPS exposure by limiting hepatic neutrophil accumulation and decreasing hepatic levels of pro-inflammatory cytokines. In addition, RvD1 treatment attenuated hepatic pyroptosis, an inflammatory form of cell death, via downregulation of pyroptosis-related genes such as GTPase family member b10 and guanylate binding protein 2, and reducing cleavage of caspase 11 and gasdermin-D. In vitro experiments with primary mouse hepatocytes and bone marrow-derived macrophages confirmed the effectiveness of RvD1 in the attenuation of pyroptosis. In summary, our data demonstrated that RvD1 treatment provided beneficial effects against liver injury and inflammation in an experimental animal model recapitulating features of severe AH in humans. Our results suggest that RvD1 may be a novel adjunct strategy to traditional therapeutic options for AH patients.
2023-09-05 | GSE220520 | GEO
Project description:Progressive lung disease remains the major cause of morbidity and mortality of people with cystic fibrosis (CF). CF lung disease evolves from mucus obstruction into non-resolving airway inflammation, bronchiectasis, and damage that impairs respiratory and fitness activity. Therefore, therapeutic strategies that promote resolution of airway inflammation in CF to alleviate the burden of airflow obstruction and improve physical capacity are of wide interest. Here, we report that the proresolving lipid mediator resolvin (Rv) D1 halts mucus-driven inflammation in CF human cells and in vivo. RvD1 dampened migration and pathogenic phenotypes of neutrophils from volunteers with CF as well as inflammatory signaling pathways of CF bronchial epithelial cells triggered by CF mucus. In mice overexpressing the β-subunit of the epithelial Na+ channel (βENaC) RvD1 administration prevented and reverted lung inflammation caused by mucus accumulation and promoted the resolution of pulmonary exacerbation caused by P. aeruginosa. RvD1 also significantly improved physical activity and energy expenditure that are impaired in βENaC mice compared to wild type littermates. These findings demonstrate efficacy of RvD1 in enhancing resolution of lung disease and chronic inflammation associated with mucus obstruction and provide proof of concept for its potential therapeutic approach in FC.
2023-10-10 | GSE234839 | GEO
Project description:Activation of the innate immune system leading to a persistent state of low-grade of tissue inflammation greatly influences the risk of developing metabolic complications associated with obesity. In this study, we characterized the inflammatory state in adipose tissue from obese patients and explored the potential of the specialized pro-resolving mediator (SPM) resolvin D1 (RvD1) to actively terminate inflammation and promote its resolution. By means of high-troughput transcritomic analysis we identified a cytokine-related molecular signature in obese omental adipose tissue, characterized by a remarkable overexpression of interleukin (IL)-6, IL-1β and IL-10 associated with a concomitant increase in macrophage infiltration, which gradually increased in a body mass index-dependent manner. RNA profiling was conducted in 4 patients with morbid obesity and 4 control subjects using the Affymetrix Human Genome U219 expression array plate containing more than 36,000 transcripts and variants (Affymetrix, Inc., Santa Clara, CA).
2016-07-28 | E-GEOD-71415 | biostudies-arrayexpress
Project description:Activation of the innate immune system leading to a persistent state of low-grade of tissue inflammation greatly influences the risk of developing metabolic complications associated with obesity. In this study, we characterized the inflammatory state in adipose tissue from obese patients and explored the potential of the specialized pro-resolving mediator (SPM) resolvin D1 (RvD1) to actively terminate inflammation and promote its resolution. By means of high-troughput transcritomic analysis we identified a cytokine-related molecular signature in obese omental adipose tissue, characterized by a remarkable overexpression of interleukin (IL)-6, IL-1β and IL-10 associated with a concomitant increase in macrophage infiltration, which gradually increased in a body mass index-dependent manner.
2016-07-28 | GSE71415 | GEO
Project description:Resolvin D1 improves allograft osteointegration and directly enhances osteoblasts differentiation
2023-02-08 | GSE224195 | GEO
Project description:Neutrophils play a pivotal role in the pathogenesis of lung ischemia-reperfusion injury. The effect of pro-resolving lipid mediators, such as Resolvin D1, on early neutrophil trafficking has not been assessed in organ transplantation. We obtained single-cell RNA sequencing of leukocytes from syngeneic left lung grafts to elucidate the genetic changes induced by recipient treatment with Resolvin D1 or vehicle.
2023-07-15 | GSE237110 | GEO
Project description:Acute limb ischemia (ALI) is associated with high morbidity and mortality rates, even with the advent of technical advances. Although myocardial infarction is one of the causes of ALI along with intraventricular thrombus formation and subsequent embolism, ALI with concomitant acute myocardial infarction (AMI) is extremely rare. Here, we report a complicated ALI case with concurrent AMI and prolonged limb ischemic duration. The cause may be attributed to thrombosis with atherosclerotic disease of the coronary and peripheral arteries triggered by dehydration. We successfully treated the patient using simultaneous revascularization in a hybrid operating room with the aid of intraoperative hemodialysis for preventing life-threatening reperfusion syndrome.
| S-EPMC6200629 | biostudies-other
Project description:OBJECTIVES:This study sought to describe the distribution of pre-intervention treated-limb ankle-brachial indices (ABIs) among patients with critical limb ischemia (CLI) undergoing percutaneous vascular intervention (PVI) or surgical revascularization (SR). BACKGROUND:CLI is diagnosed by the presence of rest pain, tissue ulceration, or gangrene due to chronic arterial insufficiency. It is unclear what fraction of patients with suspected CLI have severe peripheral artery disease (PAD) on noninvasive functional testing. METHODS:The study included patients who underwent lower extremity revascularization for CLI in a multicenter registry in Michigan from January 2012 through June 2015. ABIs were classified as normal (ABI: 0.91 to 1.40), mild-moderate (ABI: 0.41 to 0.90), and severe (ABI: ≤0.40). Pre- and post-intervention Peripheral Artery Questionnaire summary scores were assessed in a subset of patients. RESULTS:Among 10,756 patients with signs or symptoms of CLI, 9,113 (84.7%) underwent PVI and 1,643 (15.3%) underwent SR. ABIs were recorded in 4,972 (54.6%) PVI and 1,012 (61.6%) SR patients. Patients undergoing PVI had higher ABIs than those undergoing SR, with substantial variation in both groups (PVI: 0.72 ± 0.29 vs. SR: 0.61 ± 0.29; p < 0.001). Nearly a quarter of patients with compressible arteries had normal ABIs (24.0%), whereas severe PAD was uncommon (16.5%). A significant improvement in Peripheral Artery Questionnaire scores was noted after intervention across all ABI categories. CONCLUSIONS:Among patients undergoing revascularization for CLI in contemporary practice, the authors found substantial heterogeneity in pre-intervention ABIs. The disconnect between ABI results and clinical diagnosis calls into question the utility of ABIs in this population and suggests the need for standardization of functional PAD testing.
| S-EPMC6800014 | biostudies-literature
Project description:BackgroundUse of blood oxygenation level-dependent cardiovascular magnetic resonance (BOLD-CMR) to assess perfusion in the lower limb has been hampered by poor reproducibility and a failure to reliably detect post-revascularization improvements in patients with critical limb ischemia (CLI).ObjectivesThis study sought to develop BOLD-CMR as an objective, reliable clinical tool for measuring calf muscle perfusion in patients with CLI.MethodsThe calf was imaged at 3-T in young healthy control subjects (n = 12), age-matched control subjects (n = 10), and patients with CLI (n = 34). Signal intensity time curves were generated for each muscle group and curve parameters, including signal reduction during ischemia (SRi) and gradient during reactive hyperemia (Grad). BOLD-CMR was used to assess changes in perfusion following revascularization in 12 CLI patients. Muscle biopsies (n = 28), obtained at the level of BOLD-CMR measurement and from healthy proximal muscle of patients undergoing lower limb amputation (n = 3), were analyzed for capillary-fiber ratio.ResultsThere was good interuser and interscan reproducibility for Grad and SRi (all p < 0.0001). The ischemic limb had lower Grad and SRi compared with the contralateral asymptomatic limb, age-matched control subjects, and young control subjects (p < 0.001 for all comparisons). Successful revascularization resulted in improvement in Grad (p < 0.0001) and SRi (p < 0.0005). There was a significant correlation between capillary-fiber ratio (p < 0.01) in muscle biopsies from amputated limbs and Grad measured pre-operatively at the corresponding level.ConclusionsBOLD-CMR showed promise as a reliable tool for assessing perfusion in the lower limb musculature and merits further investigation in a clinical trial.
| S-EPMC4728170 | biostudies-literature
Project description: Not available
| S-EPMC4925399 | biostudies-literature