Hydrogen sulfide (H2S) is an endogenous gasotransmitter with physiologic functions similar to nitric oxide and carbon monoxide. Exogenous treatment H2S can induce a reversible hypometabolic state, which protect organs from ischemia/reperfusion injury, but whether cystathionine γ-lyase (CSE), produces H2S, has protective effects unknown. Here, human renal tissue revealed abundant expression of CSE, localized glomeruli the tubulointerstitium. Compared wild-type mice, CSE knockout mice had...

Obesity is a risk factor for SARS-CoV-2 infected patients to develop respiratory failure. Leptin produced in visceral fat might play role the deterioration mechanical ventilation. A cross sectional study was performed. The mean BMI 31 kg/m2 (range 24.8–48.4) ventilated and 26 22.4–33.5) 8 critically ill non-infected control patients. with similar as appear have significantly higher levels of serum leptin. leptin level 21.2 (6.0–85.2) vs 5.6 (2.4–8.2) ug/L controls respectively (p = 0.0007)....

Abstract Background Sepsis is a life-threatening condition accompanied by organ dysfunction subsequent to dysregulated host response infection. Up 60% of patients with sepsis develop acute kidney injury (AKI), which associated poor clinical outcome. The pathophysiology sepsis-associated AKI (sepsis-AKI) remains incompletely understood, but mitochondria have emerged as key players in the pathogenesis. Therefore, our aim was identify mitochondrial damage sepsis-AKI. Methods We conducted...

The histopathology of sepsis-associated acute kidney injury (AKI) in critically ill patients remains an understudied area. Previous studies have identified that tubular necrosis (ATN) is not the only driver sepsis-AKI. focus this study was to identify additional candidate processes may drive To do we immunohistochemically characterized histopathological and cellular features various compartments human septic kidneys. We studied following features: leukocyte subsets, fibroblast activation,...

The current COVID-19 pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has an enormous impact on human health economy. In search for therapeutic options, researchers have proposed resveratrol, a food supplement with known antiviral, anti-inflammatory, antioxidant properties as advantageous antiviral therapy SARS-CoV-2 infection. Here, we provide evidence that both resveratrol its metabolically more stable structural analog, pterostilbene, exhibit potent...

Abstract Background Severe and critical COVID-19 is characterized by pulmonary viral infection with SARS-CoV-2 resulting in local systemic inflammation. Dexamethasone (DEX) has been shown to improve outcomes critically ill patients; however, its effect on tissue remodeling, particularly collagen turnover, remains unclear. This study investigated the association between circulating extracellular matrix (ECM) remodeling neo-epitopes severity, their relationship mortality, of DEX these markers....

Damage DNA binding protein 2 (DDB2) has a high affinity for UV-damaged and been implicated in the initial steps of global genome nucleotide excision repair (NER) mammals. DDB2 binds to CUL4A forms an E3 ubiquitin ligase. In this study, we have analyzed properties vivo. The majority diffuse nucleus with diffusion rate consistent molecular mass complex. Essentially all UV-induced damage, where each molecule resides ∼2 minutes. After induction is proteolytically degraded half-life that two...

Sepsis is a life-threatening condition caused by dysregulated host response to infection. Endothelial cells (EC) are actively involved in sepsis-associated (micro)vascular disturbances and subsequent organ dysfunction. Lipopolysaccharide (LPS), Gram-negative bacterial product, can activate EC leading the expression of pro-inflammatory molecules. This process molecularly regulated specific receptors distinct, yet poorly understood intracellular signaling pathways. LPS-induced endothelial...

Abstract Background Obesity is a risk factor for adverse outcomes in COVID-19, potentially driven by chronic inflammatory state due to dysregulated secretion of adipokines and cytokines. We investigated the association between plasma COVID-19 severity, systemic inflammation, clinical parameters, outcome patients. Methods In this multi-centre prospective cross-sectional study, we collected blood samples data from The severity was classified as mild (no hospital admission), severe (ward...

Coronary artery bypass graft (CABG) surgery can result in severe postoperative organ failure. During CABG surgery, cardiopulmonary (CPB) with cardiac arrest is often used (on-pump CABG), which results a systemic inflammatory response. To reduce this response, off-pump was reintroduced, thereby avoiding CPB. There increasing evidence that the endothelium plays an important role pathophysiology of failure after surgery. In study, 60 patients who were scheduled for elective randomized to have...

Microglia are a proliferative population of resident brain macrophages that under physiological conditions self-renew independent hematopoiesis. innate immune cells actively surveying the and earliest responders to injury. During aging, microglia elicit an enhanced response also referred as 'priming'. To date, it remains unknown whether telomere shortening affects capacity induces priming microglia. We addressed this issue using early (first-generation G1 mTerc(-/-) )- late-generation...

Klotho is a renal protein involved in phosphate homeostasis, which downregulated disease. It has long been considered an antiaging factor. Two gene transcripts are thought to encode membrane-bound and secreted Klotho. Indeed, soluble detectable bodily fluids, but the relative contributions of secretion shedding unknown. Recent advances RNA surveillance reveal that premature termination codons, as present alternative mRNA (for Klotho), prime mRNAs for degradation by nonsense-mediated decay...

Individuals with type 2 diabetes mellitus have increased rates of macrovascular disease (MVD). Endothelial progenitor cells (EPCs), circulating angiogenic (CACs) and smooth muscle (SMPCs) are suggested to play a role in the pathogenesis MVD. The relationship between vasoregenerative EPCs or CACs damaging SMPCs development accelerated MVD is still unknown. We tried elucidate whether EPC, CAC SMPC numbers differentiation capacities vitro differ patients without Peripheral blood was obtained...

In patients with sepsis-induced multi-organ dysfunction syndrome, diverging patterns of oedema formation and loss function in organs such as lung kidney suggest that endothelial permeability-regulating molecular responses are differentially regulated. This potential differential regulation has been insufficiently studied at the level components adherens tight junctions. We hypothesized a by cells sepsis takes place an organ-specific manner. addressed our hypothesis studying quantitative real...

Abstract Vascular permeability and plasma leakage are immune-pathologies of severe dengue virus (DENV) infection, but the mechanisms underlying exacerbated inflammation during DENV pathogenesis unclear. Here, we demonstrate that TLR2, together with its co-receptors CD14 TLR6, is an innate sensor particles inducing inflammatory cytokine expression impairing vascular integrity in vitro. Blocking TLR2 prior to infection vitro abrogates NF-κB activation while TLR6 block has a moderate effect....

Acute kidney injury (AKI) is associated with the abrupt loss of function. Oxidative stress plays an important role in pathophysiology AKI. Free thiols (R-SH) are crucial components extracellular antioxidant machinery and reliably reflect systemic oxidative stress. Lower levels represent higher In this preliminary study, we hypothesized that plasma-free AKI upon admission to intensive care unit (ICU). 301 critically ill patients were included. Plasma samples taken admission, albumin-adjusted...

Acute respiratory distress syndrome (ARDS) is pathologically characterized by diffuse alveolar damage (DAD) and associated with high morbidity mortality rates. Remodeling of the extracellular matrix (ECM), which pivotal for tissue repair organ recovery, may play a large role in persistent ARDS. This study investigated compositional changes ECM different DAD stages Paraffin-embedded lung sections collected during autopsy or from post-transplant lungs were obtained patients ARDS (n=28)...

Abstract UV-damaged DNA-binding protein (UV-DDB) is essential for global genome repair (GGR) of UV-induced cyclobutane pyrimidine dimers (CPD). Unlike human cells, rodent epidermal cells are deficient in GGR CPDs and express a subunit UV-DDB, DDB2, at low level. In this study, we generated mice (K14-DDB2) ectopically expressing mouse DDB2 elevated levels. Enhanced expression both delayed the onset squamous cell carcinoma decreased number tumors per chronically UV-B light-exposed hairless...

Rodent models of both aging and obesity are characterized by inflammation in specific brain regions, notably the corpus callosum, fornix, hypothalamus. Microglia, resident macrophages central nervous system, important for development, neural support homeostasis. However, effects diet lifestyle on microglia during only partly understood. Here, we report alterations phenotype functions different regions mice a high-fat (HFD) or low-fat (LFD) response to voluntary running wheel exercise. We...

Abstract Sepsis is a systemic inflammatory response to infections associated with organ failure that the most frequent cause of death in hospitalized patients. Exaggerated endothelial activation, altered blood flow, vascular leakage, and other disturbances synergistically contribute sepsis-induced failure. The underlying signaling events proinflammatory activation are not well understood, yet they likely consist molecular pathways act an endothelium-specific manner. We found LPS, critical...

Abstract Background The mechanisms driving acute kidney injury (AKI) in critically ill COVID-19 patients are unclear. We collected biopsies from AKI within 30 min after death order to examine the histopathology and perform mRNA expression analysis of genes associated with renal injury. Methods This study involved analyses postmortem ( n = 6) bacterial sepsis 27). Normal control tissue was obtained undergoing total nephrectomy 12). mean length ICU admission-to-biopsy days for 3–4 patients....