Acute Inflammatory Diseases Research Articles

Glomerular endothelial glycocalyx-derived heparan sulfate inhibits glomerular leukocyte influx and attenuates experimental glomerulonephritis.

Proliferative forms of glomerulonephritis are characterized by the influx of leukocytes, albuminuria, and loss of kidney function. The glomerular endothelial glycocalyx is a thick carbohydrate layer that covers the endothelium and is comprised of heparan sulfate (HS), which plays a pivotal role in glomerular inflammation by facilitating endothelial-leukocyte trafficking. We hypothesize that the exogenous glomerular glycocalyx may reduce the glomerular influx of inflammatory cells during glomerulonephritis. Indeed, administration of mouse glomerular endothelial cell (mGEnC)-derived glycocalyx constituents, or the low-molecular-weight heparin enoxaparin, reduced proteinuria in mice with experimental glomerulonephritis. Glomerular influx of granulocytes and macrophages, as well as glomerular fibrin deposition, was reduced by the administration of mGEnC-derived glycocalyx constituents, thereby explaining the improved clinical outcome. HSglx also inhibited granulocyte adhesion to human glomerular endothelial cells in vitro. Notably, a specific HSglx fraction inhibited both CD11b and L-selectin binding to activated mGEnCs. Mass spectrometry analysis of this specific fraction revealed six HS oligosaccharides, ranging from tetra- to hexasaccharides with 2-7 sulfates. In summary, we demonstrate that exogenous HSglx reduces albuminuria during glomerulonephritis, which is possibly mediated via multiple mechanisms. Our results justify the further development of structurally defined HS-based therapeutics for patients with (acute) inflammatory glomerular diseases, which may be applicable to non-renal inflammatory diseases as well.

Modulation of Innate Immune Memory Dynamics by Subcellular Reactive Oxygen Species.

Significance: Innate immune cells adopt distinct memory states during the pathogenesis of acute and chronic inflammatory diseases. Intracellular generations of reactive oxygen species (ROS) play key roles during the programming dynamics of innate immune cells such as monocytes and macrophages. Recent Advances: ROS modulate the adaptation of innate leukocytes to varying intensities and durations of inflammatory signals, facilitate fundamental reprogramming dynamics such as priming, tolerance, and exhaustion, in addition to fundamental processes of proliferation, differentiation, phagocytosis, chemotaxis, as well as expression of pro- and anti-inflammatory mediators. ROS can be generated at distinct subcellular compartments including cellular membrane, mitochondria, and peroxisome. Complex inflammatory signals may finely regulate ROS generation within distinct subcellular compartments, which in turn may differentially facilitate innate memory dynamics. Critical Issues: Complex inflammatory signals with varying strengths and durations may differentially trigger ROS generation at peroxisome, mitochondria, and other subcellular organelles. Peroxisomal or mitochondrial ROS may facilitate the assembly of distinct signaling platforms involved in the programming of memory innate leukocytes. Despite the emerging connection of subcellular ROS with innate immune memory, underlying mechanisms are still not well defined. Future Directions: Recent important discoveries linking subcellular ROS and innate memory as critically reviewed here hold novel translational relevance related to acute and chronic inflammatory diseases. Capitalizing on these novel findings, future systems studies that use next-generation single-cell dynamic analyses in response to complex inflammatory environments are urgently needed to comprehensively decipher the programming dynamics of innate immune memory, finely modulated by subcellular ROS. Antioxid. Redox Signal. 39, 1027-1038.

Potential of extracellular vesicles for early prediction of severity and potential risk stratification in critical inflammatory diseases.

Some acute inflammatory diseases are often exacerbated during or after hospitalization, leading to some severe manifestations like systemic inflammatory response syndrome, multiple organ failure, and high mortality. Early clinical predictors of disease severity are urgently needed to optimize patient management for better prognosis. The existing clinical scoring system and laboratory tests cannot circumvent the problems of low sensitivity and limited specificity. Extracellular vesicles (EVs) are heterogeneous nanosecretory vesicles containing various biomolecules related to immune regulation, inflammation activation, and inflammation-related complications. This review provides an overview of EVs as inflammatory mediators, inflammatory signaling pathway regulators, promoters of inflammatory exacerbation, and markers of severity and prognosis. Currently, although relevant biomarkers are clinically available or are in the preclinical research stage, searching for new markers and detection methods is still warranted, as the problems of low sensitivity/specificity, cumbersome laboratory operation and high cost still plague clinicians. In-depth study of EVs might open a door in the search for novel predictors.

Ergolide covalently binds NLRP3 and inhibits NLRP3 inflammasome-mediated pyroptosis

BackgroundNLR family pyrin domain-containing 3 (NLRP3)-mediated pyroptosis plays a key role in various acute and chronic inflammatory diseases. Targeted inhibition of NLRP3-mediated pyroptosis may be a potential therapeutic strategy for various inflammatory diseases. Ergolide (ERG) is a sesquiterpene lactone natural product derived from the traditional Chinese medicinal herb, Inula britannica. ERG has been shown to have anti-inflammatory and anti-cancer activities, but the target is remains unknown. Hypothesis/PurposeThis study performed an in-depth investigation of the anti-inflammatory mechanism of ERG in NLRP3-mediated pyroptosis and NLPR3 inflammasome related sepsis and acute lung injury model. MethodsELISA and Western blot were used to determine the IL-1β and P20 levels. Co-immunoprecipitation assays were used to detect the interaction between proteins. Drug affinity response target stability (DARTS) assays were used to explore the potential target of ERG. C57BL/6J mice were intraperitoneally injected with E. coli DH5α (2 × 109 CFU/mouse) to establish a sepsis model. Acute lung injury was induced by intratracheal administrationof lipopolysaccharide in wild-type mice and NLRP3 knockout mice with or without ERG treatment. ResultsWe showed that ERG is an efficient inhibitor of NLRP3-mediated pyroptosis in the first and second signals of NLRP3 inflammasome activation. Furthermore, we demonstrated that ERG irreversibly bound to the NACHT domain of NLRP3 to prevent the assembly and activation of the NLRP3 inflammasome. ERG remarkably improved the survival rate of wild-type septic mice. In lipopolysaccharide-induced acute lung injury model, ERG alleviated acute lung injury of wild-type mice but not NLRP3 knockout mice. ConclusionOur results revealed that the anti-pyroptosis effect of ERG are dependent on NLRP3 and NLRP3 NACHT domain is ERG’s direct target. Therefore, ERG can serve as a precursor drug for the development of novel NLRP3 inhibitors to treat NLRP3 inflammasome mediated inflammatory diseases.

A novel galactoxylan derived from Viola diffusa alleviates LPS-induced acute lung injury via antagonizing P-selectin-mediated adhesion function

Acute lung injury (ALI) greatly threatens human health worldwide. P-selectin is a potential target for the treatment of acute inflammatory diseases, and natural polysaccharides exhibit high-affinity for P-selectin. Viola diffusa, a traditional Chinese herbal, shows strong anti-inflammatory effects, but pharmacodynamic substances and underlying mechanisms are still unclear. In this study, a galactoxylan polysaccharide (VDPS) derived from Viola diffusa was isolated and characterized, evaluated the protective effect on LPS induced ALI and underlying mechanism. VDPS significantly alleviated LPS-induced pathological lung injury, and decreased the numbers of total cells and neutrophils as well as the total protein contents in the bronchoalveolar lavage fluid (BALF). Moreover, VDPS reduced proinflammatory cytokine production both in BALF and lung. Interestingly, VDPS significantly restrained the activation of NF-κB signaling in the lung of LPS-exposed mice, but it cannot inhibit LPS-induced inflammation in human pulmonary microvascular endothelial cells (HPMECs) in vitro. Additionally, VDPS disrupted neutrophil adhesion and rolling on the activated HPMECs. VDPS cannot impact the expression or cytomembrane translocation of endothelial P-selectin, but remarkably interrupt the binding of P-selectin and PSGL-1. Overall, this study demonstrated that VDPS can alleviate LPS-induced ALI via inhibiting P-selectin-dependent adhesion and recruitment of neutrophils on the activated endothelium, providing a potential treatment strategy for ALI.

Basic therapy for viral diseases of the upper respiratory tract

The high prevalence of inflammatory diseases of the upper respiratory tract brings this pathology to the forefront, occupying up to 90% of cases of contacting specialists among all infectious diseases. The main etiological factor in the occurrence of acute inflammatory diseases of the upper respiratory tract, such as rhinitis, rhinosinusitis, pharyngitis, is the defeat of a viral agent. At the same time, the damaging viral agents are extremely diverse. In turn, an incorrectly selected initial therapy can lead to a weakening of local nonspecific immunity, which in turn forms a starting point for the attachment of a bacterial infection and the development of acute bacterial rhinosinusitis. Due to the high prevalence of infections of the upper respiratory tract and unreasonable systemic antibiotic therapy, it is the main factor contributing to the growth of antibacterial resistance, and taking into account the wide range of infectious microbiota that contributes to the development of chronic pathology, the selection of adequate drugs for the treatment of inflammatory diseases of the upper respiratory tract remains relevant. If it is inappropriate to use antibacterial therapy, homeopathic preparations can be used both as monotherapy for uncomplicated forms of a viral disease, and in combination in cases where the safety of prescribed drugs is important to the patient. This is especially true in childhood, when the doctor is limited in the use of medicines. The purpose of this work is to familiarize physicians with the epidemiology, symptoms and modern principles of treatment of inflammatory diseases of the upper respiratory tract with an emphasis on risk factors. The analysis of Russian-language and English-language publications was carried out using the databases: eLibrary, PubMed, Russian Science Citation Index, Springer, Scopus, Scientific Research, Crossref.

Current possibilities of using silver proteinate in the treatment of inflammatory diseases of the nose and paranasal sinuses

The article evaluates the possibility of using silver proteinate to treat acute inflammatory diseases of the nasal cavity and paranasal sinus mucosa, as well as their complications. Acute rhinitis and rhinosinusitis are among the most common upper respiratory diseases. Viral pathogens are the main agents that trigger the pathological process. At the same time, the bacterial superinfection in some cases may develop due to viral infection, which promotes further development of lingering clinical symptoms up to a complicated course of the disease. The course of rhinosinusitis with underlying COVID-19 infection can be complicated by fungal superinfection and postnasal drip. For these reasons, topical drugs that could be used in the early stages of these conditions should have a number of properties, such as activity against most respiratory viruses and aetiologically significant bacterial pathogens; lack of opportunity to evolute and implement rapid resistance mechanisms in microorganisms; additive effects with other antibacterial drugs; acceleration of regeneration of the nasal cavity and paranasal sinus mucosa with underlying infectious alteration; vasoconstrictive and anti-inflammatory action, without causing an addictive effect, which enables repeated use of the drug in chronic diseases, as well as the absence of local and systemic toxic effects. Sialor (silver proteinate) has all the specified characteristics that were proved in various studies, and consistently demonstrated high clinical efficacy for many years.

Efficiency of topical bacterial lysates in inflammatory diseases of the oral cavity and pharynx

Acute and chronic infectious and inflammatory diseases of the upper respiratory tract occupy one of the leading places in the structure of morbidity of the population of the world and remain the most frequent cause of patients seeking medical care. The prevalence and frequency of respiratory infectious diseases make a significant contribution to the structure of the causes of temporary disability, which entails negative socio-economic consequences. Specific attention in the current epidemic season is attracted by the change in the traditional structure of pathogens associated with several strict anti-epidemic measures during the COVID-19 pandemic, as well as a decrease in the activity of other pathogens during the active circulation of SARS-CoV-2. In this aspect, the increased resistance of pathogens to etiotropic drugs and insufficiency of the arsenal of pathogenic drugs dictate the need to search for alternative approaches to the treatment of inflammatory diseases of the mouth and throat. The main purpose of non-specific preventive measures of acute and recurrent diseases of the oral cavity and pharynx is to reduce bacterial content of mucous membranes by various pathogens and to activate own protective anti-infective mechanisms. In clinical practice medicines which contain bacterial lysates are considered to be an effective part of treatment of upper respiratory tract’s inflammatory diseases. They allow achieving elimination of a pathogenic organism and also help to restore autoregulation of immune response in the whole organism, reduce the frequency of infectious diseases. Topical bacterial lysates, acting directly in the locus of inflammation, do not harm the human microbiome, have a high safety profile, combine well with other medicines and can be used for patients of different ages. Topical immunotherapy has a significant preventive effect, preventing possible complications and improving the quality of life. The use of Imudon and IRS 19 leads to positive clinical and immunological shifts and promotes the efficiency of rehabilitation and preventive measures.

Antioxidative and anti-inflammatory effect of ethanol extracts from Magnolia kobusDC on LPS-induced in vitroand in vivomodel

Abstract Magnolia kobusDC (M. kobus) has biological effects such as antioxidant, anti-inflammatory and antibacterial properties in its flower, bud, and stem bark extracts. Despite of diverse effectiveness of M. kobus, the pharmacological effects supporting inhibition of oxidation and inflammation on acute lung inflammation states have not been studied yet. The purpose of this study was to evaluate the pharmacological activity of M. kobusleaf ethanol extract (MkDE) by antioxidant and anti-inflammatory effects on acute lung inflammatory diseases. The antioxidant and anti-inflammatory effects of MkDE was evaluated using ROS detection assay, NO assay, qPCR, ELISA, and Western blot on LPS-induced macrophages. The therapeutic effect of MkDE was investigated in vivooxidative and inflammatory responses by histological observations, qPCR, ELISA, and Western blot using the LPS-induced acute lung inflammation mouse model. MkDE decreased ROS production and protein of Nrf2. MkDE showed a protective effect against H 2O 2as well as a decrease in NO production. MkDE reduced the levels of pro-inflammatory cytokines and chemokine, the activation of COX-2 and iNOS, and NF-κB translocation in LPS-induced macrophage. The intraperitoneal injection of MkDE showed to decrease the lung/body weights, infiltrated inflammatory cells into the lung alveoli, pro-inflammatory mediators, and serum released proteins. Furthermore, MkDE inhibited the activation of Nrf2, COX-2 and NF-κB in LPS-induced acute lung tissue. MkDE exhibits the pharmacological effect by reducing oxidative and inflammatory mediators on LPS-induced macrophages and acute lung inflammation mouse model. Taken together, MkDE might be used to treat acute lung disease.

Electromagnetic Induction for Treatment of Unspecific Back Pain: A Prospective Randomized Sham-Controlled Clinical Trial

To evaluate the effects of high-energy pulsed electromagnetic fields on unspecific back pain. A prospective, randomized, sham-controlled clinical trial with repeated measurements was performed. The study included 5 visits (V0 to V4) with 3 interventions during V1, V2 and V3. Sixty-one patients aged between 18 and 80 years with unspecific back pain (acute inflammatory diseases and specific causes were reasons for exclusion) were included. The treatment group (n = 31) received 1-2 pulses/s, with an intensity of 50 mT, and an electric field strength of at least 20 V/m on 3 consecutive weekdays for 10 min each time. The control group (n = 30) received a comparable sham therapy. Pain intensity (visual analogue scale), local oxyhaemoglobin saturation, heart rate, blood pressure, and perfusion index were evaluated before (b) and after (a) V1 and V3 interventions. Change in visual analogue scale for V1 (ChangeV1a-b) and V3 (ChangeV3a-b), and ChangeData between V3a and V1b (ChangeV3a-V1b) for the remaining data were calculated (results were mean (standard deviation) (95% confidence interval; 95% CI)). Concerning the visual analogue scale: (i) compared with the control group, the treatment group had higher ChangeV1a-b (-1.25 (1.76) (95% CI -1.91 to -0.59) vs -2.69 (1.74) (95% CI -3.33 to -2.06), respectively), and comparable Change V3a-b (-0.86 (1.34) (95% CI -1.36 to -0.36) vs -1.37 (1.03) (95% CI -1.75 to 0.99), respectively); and (ii) there was a significant marked decrease in Change V3a-1b in the treatment group compared with the control group (-5.15 (1.56) (95% CI -5.72 to -4.57) vs -2.58 (1.68) (95% CI -3.21 to -1.96), p = 0.001, respectively). There was no significant ChangeV3a-V1b in local oxyhaemoglobin saturation, heart rate, blood pressure or perfusion index between the 2 groups and for the same group (before vs after). Non-thermal, non-invasive electromagnetic induction therapy had a significant and rapid influence on unspecific back pain in the treatment group.

PR1P, a VEGF-stabilizing peptide, reduces injury and inflammation in acute lung injury and ulcerative colitis animal models.

Acute Respiratory Distress Syndrome (ARDS) and Ulcerative Colitis (UC) are each characterized by tissue damage and uncontrolled inflammation. Neutrophils and other inflammatory cells play a primary role in disease progression by acutely responding to direct and indirect insults to tissue injury and by promoting inflammation through secretion of inflammatory cytokines and proteases. Vascular Endothelial Growth Factor (VEGF) is a ubiquitous signaling molecule that plays a key role in maintaining and promoting cell and tissue health, and is dysregulated in both ARDS and UC. Recent evidence suggests a role for VEGF in mediating inflammation, however, the molecular mechanism by which this occurs is not well understood. We recently showed that PR1P, a 12-amino acid peptide that binds to and upregulates VEGF, stabilizes VEGF from degradation by inflammatory proteases such as elastase and plasmin thereby limiting the production of VEGF degradation products (fragmented VEGF (fVEGF)). Here we show that fVEGF is a neutrophil chemoattractant in vitro and that PR1P can be used to reduce neutrophil migration in vitro by preventing the production of fVEGF during VEGF proteolysis. In addition, inhaled PR1P reduced neutrophil migration into airways following injury in three separate murine acute lung injury models including from lipopolysaccharide (LPS), bleomycin and acid. Reduced presence of neutrophils in the airways was associated with decreased pro-inflammatory cytokines (including TNF-α, IL-1β, IL-6) and Myeloperoxidase (MPO) in broncho-alveolar lavage fluid (BALF). Finally, PR1P prevented weight loss and tissue injury and reduced plasma levels of key inflammatory cytokines IL-1β and IL-6 in a rat TNBS-induced colitis model. Taken together, our data demonstrate that VEGF and fVEGF may each play separate and pivotal roles in mediating inflammation in ARDS and UC, and that PR1P, by preventing proteolytic degradation of VEGF and the production of fVEGF may represent a novel therapeutic approach to preserve VEGF signaling and inhibit inflammation in acute and chronic inflammatory diseases.

A peptide derived from HSP60 reduces proinflammatory cytokines and soluble mediators: a therapeutic approach to inflammation.

Cytokines are secretion proteins that mediate and regulate immunity and inflammation. They are crucial in the progress of acute inflammatory diseases and autoimmunity. In fact, the inhibition of proinflammatory cytokines has been widely tested in the treatment of rheumatoid arthritis (RA). Some of these inhibitors have been used in the treatment of COVID-19 patients to improve survival rates. However, controlling the extent of inflammation with cytokine inhibitors is still a challenge because these molecules are redundant and pleiotropic. Here we review a novel therapeutic approach based on the use of the HSP60-derived Altered Peptide Ligand (APL) designed for RA and repositioned for the treatment of COVID-19 patients with hyperinflammation. HSP60 is a molecular chaperone found in all cells. It is involved in a wide diversity of cellular events including protein folding and trafficking. HSP60 concentration increases during cellular stress, for example inflammation. This protein has a dual role in immunity. Some HSP60-derived soluble epitopes induce inflammation, while others are immunoregulatory. Our HSP60-derived APL decreases the concentration of cytokines and induces the increase of FOXP3+ regulatory T cells (Treg) in various experimental systems. Furthermore, it decreases several cytokines and soluble mediators that are raised in RA, as well as decreases the excessive inflammatory response induced by SARS-CoV-2. This approach can be extended to other inflammatory diseases.

Dual Functioned Hexapeptide-Coated Lipid-Core Nanomicelles Suppress Toll-Like Receptor-Mediated Inflammatory Responses through Endotoxin Scavenging and Endosomal pH Modulation.

Excessive activation ofToll-like receptor (TLR) signaling pathways and the circulating endotoxin are key players in the pathogenesis of many acute and chronic inflammatory diseases. Regulation of TLR-mediated inflammatory responses by bioactive nanodevices represents a promising strategy for treating these diseases. In searching for novel, clinically applicable nanodevices with potent TLR inhibitory activities, three types of hexapeptide-modified nano-hybrids with different cores of phospholipid nanomicelles, liposomes, and poly(lactic-co-glycolic acid) nanoparticles are constructed. Interestingly, only the peptide-modified lipid-core nanomicelles (M-P12) display potent TLR inhibitory activities. Further mechanistic studies disclose that lipid-core nanomicelles have a generic property to bind to and scavenge lipophilic TLR ligands including lipopolysaccharide to block the ligand-receptor interaction and down-regulate the TLR signaling extracellularly. In addition, the peptide modification enables M-P12 a unique capability to modulate endosomal acidification upon being endocytosed into macrophages, which subsequently regulates the endosomal TLR signal transduction. In an acute lung injury mouse model, intratracheal administration of M-P12 can effectively target lung macrophages and reduce lung inflammation and injuries. This work defines a dual mechanism of action of the peptide-modified lipid-core nanomicelles in regulating TLR signaling, and provides new strategies for the development of therapeutic nanodevices for treating inflammatory diseases.

Analysis of the development dynamics of cough syndrome in acute nasopharyngitis with intoxication syndrome

Introduction. Although acute cough in acute inflammatory diseases of the upper respiratory tract seems to be a minor problem and can be stopped on its own, it holds the leading position among all reasons for population receiving health care due to significant decrease in life quality.Purpose. To analyze the cough severity in patients with acute nasopharyngitis with intoxication syndrome in the treatment of systemic non-steroidal anti-inflammatory drugs (NSAIDs) and local interferon therapy.Materials and methods. The study included 62 patients with acute nasopharyngitis with intoxication syndrome, in the period from the onset of the first symptoms to the visit to the doctor was no more than 24 hours. They were divided into 2 groups: group 1 − 32 people (14 men, 18 women, age 34.4 ± 10.3 years) received traditional systemic therapy with NSAIDs, group 2 − 30 people (13 men, 17 women, age 41.1 ± 13.7 years) received interferon-α2b intranasally. Cough severity was assessed using a 3-point visual analog scale (VAS) on the day of admission and for the next 7 days.Results. On the 1st day dry cough was observed in 62.5–63.3% of cases. Starting from the 3rd day of observation, there were statistically significant differences in the intensity of this symptom between the groups. In the traditional therapy of NSAIDs, an increase in the number of patients with a complaint of cough, and an increase in its severity compared with the first day of observation was revealed. They lasted until the 6th day of illness, which was explained by the spread of the inflammatory process to the trachea and bronchi. In the treatment of local interferon therapy, cough regression was noted on day 4 in 83.3% of cases, with its complete disappearance in this group on day 6. The total duration of cough in group 1 was 6.0 (5.0; 8.0) days, in group 2 – 2.0 (1.0; 3.0) days.Conclusion. In acute inflammatory diseases of the upper respiratory tract, cough in the absence of prescribing drugs that affect this symptom persists on the eighth day of observation in 56.2% of patients with traditional therapy with systemic NSAIDs.

Effects of brake wear nanoparticles on the protection and repair functions of the airway epithelium

Long term exposure to particulate air pollution is known to increase respiratory morbidity and mortality. In urban areas with dense traffic most of these particles are generated by vehicles, via engine exhaust or wear processes. Non-exhaust particles come from wear processes such as those concerning brakes and their toxicity is little studied. To improve our understanding of the lung toxicity mechanisms of the nanometric fraction of brake wear nanoparticles (BWNPs), we studied whether these particles affect the barrier properties of the respiratory epithelium considering particle translocation, mucus production and repair efficiency. The Calu-3 cell line grown in two-compartment chambers was used to mimic the bronchial epithelial barrier. BWNPs detected by single-particle ICP-MS were shown to cross the epithelial tissue in small amounts without affecting the barrier integrity properties, because the permeability to Lucifer yellow was not increased and there was no cytotoxicity as assessed by the release of lactate-dehydrogenase. The interaction of BWNPs with the barrier did not induce a pro-inflammatory response, but increased the expression and production of MU5AC, a mucin, by a mechanism involving the epidermal growth factor receptor pathway. During a wound healing assay, BWNP-loaded cells exhibited the same ability to migrate, but those at the edge of the wound showed higher 5-ethynyl-2′-deoxyuridine incorporation, suggesting a higher proliferation rate. Altogether these results showed that BW.NPs do not exert overt cytotoxicity and inflammation but can translocate through the epithelial barrier in small amounts and increase mucus production, a key feature of acute inflammatory and chronic obstructive pulmonary diseases. Their loading in epithelial cells may impair the repair process through increased proliferation.

Phenotypic changes in low-density lipoprotein particles as markers of adverse clinical outcomes in COVID-19.

Low-density lipoprotein (LDL) plasma concentration decline is a biomarker for acute inflammatory diseases, including coronavirus disease-2019 (COVID-19). Phenotypic changes in LDL during COVID-19 may be equally related to adverse clinical outcomes. Individuals hospitalized due to COVID-19 (n=40) were enrolled. Blood samples were collected on days 0, 2, 4, 6, and 30 (D0, D2, D4, D6, and D30). Oxidized LDL (ox-LDL), and lipoprotein-associated phospholipase A2 (Lp-PLA2) activity were measured. In a consecutive series of cases (n=13), LDL was isolated by gradient ultracentrifugation from D0 and D6 and was quantified by lipidomic analysis. Association between clinical outcomes and LDL phenotypic changes was investigated. In the first 30days, 42.5% of participants died due to Covid-19. The serum ox-LDL increased from D0 to D6 (p<0.005) and decreased at D30. Moreover, individuals who had an ox-LDL increase from D0 to D6 to over the 90th percentile died. The plasma Lp-PLA2 activity also increased progressively from D0 to D30 (p<0.005), and the change from D0 to D6 in Lp-PLA2 and ox-LDL were positively correlated (r=0.65, p<0.0001). An exploratory untargeted lipidomic analysis uncovered 308 individual lipids in isolated LDL particles. Paired-test analysis from D0 and D6 revealed higher concentrations of 32 lipid species during disease progression, mainly represented by lysophosphatidyl choline and phosphatidylinositol. In addition, 69 lipid species were exclusively modulated in the LDL particles from non-survivors as compared to survivors. Phenotypic changes in LDL particles are associated with disease progression and adverse clinical outcomes in COVID-19 patients and could serve as a potential prognostic biomarker.

Who is in the driver's seat? Parvimonas micra: An understudied pathobiont at the crossroads of dysbiotic disease and cancer.

Recent advances in our understanding of microbiome composition at sites of inflammatory dysbiosis have triggered a substantial interest in a variety of historically understudied bacteria, especially among fastidious obligate anaerobes. A plethora of new evidence suggests that these microbes play outsized roles in establishing synergistic polymicrobial infections at many different sites in the human body. Parvimonas micra is a prime example of such an organism. Despite being almost completely uncharacterized at the genetic level, it is one of the few species commonly detected in abundance at multiple mucosal sites experiencing either chronic or acute inflammatory diseases, and more recently, it has been proposed as a discriminating biomarker for multiple types of malignancies. In the absence of disease, P. micra is commonly found in low abundance, typically residing within the oral cavity and gastrointestinal tract. P. micra exhibits the typical features of an inflammophilic organism, meaning its growth actually benefits from active inflammation and inflammatory tissue destruction. In this mini-review, we will describe our current understanding of this underappreciated but ubiquitous pathobiont, specifically focusing upon the role of P. micra in polymicrobial inflammatory dysbiosis and cancer as well as the key emerging questions regarding its pathobiology. Through this timely work, we highlight Parvimonas micra as a significant driver of disease and discuss its unique position at the crossroads of dysbiosis and cancer.

ЛУЧЕВАЯ ДИАГНОСТИКА ЗАБОЛЕВАНИЙ ПОДЖЕЛУДОЧНОЙ ЖЕЛЕЗЫ

The article discusses acute and chronic inflammatory diseases and tumors of the pancreas, the diagnosis of these diseases using x-ray methods. A comparative analysis of the effectiveness of various radiological methods in the diagnosis of pancreatic patho

HnRNPA2B1 Aggravates Inflammation by Promoting M1 Macrophage Polarization.

Macrophages have critical contributions to both acute and chronic inflammatory diseases, for example, bowel disease and obesity, respectively. However, little is known about the post-transcriptional regulatory mechanisms in macrophage-mediated inflammatory diseases. hnRNPA2B1 (A2B1) is an RNA binding protein for mRNA fate determination. We showed that hnRNPA2B1 mRNA levels were increased in colon in dextran sodium sulfate (DSS)-induced colitis mice and in epididymal white adipose tissue (eWAT) and spleen of high-fat-diet (HFD)-induced obese mice. Consistently, mice with haploinsufficiency of A2B1 (A2B1 HET) are protected against DSS-induced acute colitis and HFD-induced obesity, with decreased M1 macrophages polarization in colon, eWAT and spleen. Mechanistically, A2B1 mRNA and protein levels were increased in LPS-stimulated RAW 264.7 macrophages, and A2B1 enhanced RNA stability of pro-inflammatory genes Tnfα, Il-6 and Il-1β for the regulation of macrophages polarization. Interestingly, A2B1 HET mice exhibited reduced white fat expansion, which was influenced by macrophages, since conditioned medium from macrophages with A2B1 manipulation significantly changed preadipocyte proliferation. Our data demonstrate that A2B1 plays a vital role in macrophage-mediated inflammation via regulating mRNA stability, suggesting that A2B1 may be served as a promising target for the intervention of acute and chronic inflammatory diseases.

Serum Ferritin Levels in Severe Obstructive Sleep Apnea.

Obstructive sleep apnea (OSA) has been associated with various acute and chronic inflammatory diseases, as has serum ferritin, an intracellular iron storage protein. Little is known about the relationship between severity of OSA and serum ferritin levels in otherwise healthy subjects. In this study, all polysomnographic recordings, serum levels of ferritin, C-reactive protein (CRP), and hemoglobin, as well as patient files from 90 consecutive, otherwise healthy individuals with suspected OSA who presented to a tertiary sleep medical center were retrospectively analyzed. For comparison, three groups were formed based on apnea-hypopnea index (AHI; none or mild OSA: <15/h vs. moderate OSA: 15-30/h vs. severe OSA: >30/h). Serum ferritin levels were significantly positively correlated with AHI (r = 0.3240, p = 0.0020). A clear trend of higher serum ferritin levels was found when patients with severe OSA were compared to those without or with mild OSA. Serum CRP and serum hemoglobin levels did not differ significantly among OSA severity groups. Age and body-mass index (BMI) tended to be higher with increasing OSA severity. The BMI was significant higher in patients with severe OSA compared to those without or with mild (p < 0.001). Therefore, serum ferritin levels may provide a biochemical surrogate marker for OSA severity.