Anaphylaxis should be clinically diagnosed with immediate recognition, whereas, despite advances in the field of allergy, the symptoms of anaphylaxis remain to be under-recognized, diagnosis is often missed, and treatment is often delayed. Anaphylaxis presents with symptoms in a spectrum of severity, ranging from mild objective breathing problems to circulatory shock and/or collapse. Indeed, anaphylaxis management frequently relies on a 'one-size-fits-all approach rather than a precision medicine care model, despite the evidence that anaphylaxis is a heterogeneous condition with differences in causative agents, clinical presentation, and host susceptibility. The key important risk factors for severe anaphylaxis and mortality are certain age groups or certain stages of life (infants, elderly and pregnant women), augmenting factors (physical exercise, alcohol consumption, menstruation, acute infections), concurrent use of some medications (beta-adrenergic blockers [β-blockers] and angiotensin-converting enzyme [ACE] inhibitors, non-steroidal anti-inflammatory drugs [NSAIDs], and proton pump inhibitors [PPIs]), and concomitant diseases (i.e. asthma, cardiovascular disease, mastocytosis). The present review aims to collectively address the patient groups who are at high risk of having anaphylaxis, those who have a more severe course, those that are difficult to diagnose, and require a special approach in treatment. Therefore, the risky populations like the elderly, pregnant women, patients receiving β-blockers or ACE inhibitors, those with concomitant cardiovascular diseases, asthma, and mastocytosis, or those having higher baseline serum tryptase levels are discussed, including their clinical presentations and treatment strategies. Additionally, anaphylaxis during the perioperative period is addressed.

BACKGROUND: The specific functions of RNA N6-methyladenosine (m6A) modifications in the glioma tumor microenvironment (TME) and glioma patient prognosis and treatment have not been determined to date. OBJECTIVE: The objective of the study was to determine the role of m6A modifications in glioma TME. METHODS: Nonnegative matrix factorization (NMF) methods were used to determine m6A clusters and m6A gene signatures based on 21 genes relating to m6A modifications. TME characteristics for each m6A cluster and m6A gene signature were quantified by established m6A score. The utility of m6A score was validated in immunotherapy and other antiangiogenic treatment cohorts. RESULTS: Three m6A clusters were identified among 3,395 glioma samples, and they were linked to different biological activities and clinical outcomes. The m6A clusters were highly consistent with immune profiles known as immune-inflamed, immune-excluded, and immune-desert phenotypes. Clusters within individual tumors could predict glioma inflammation, molecular subtypes, TME stromal activity, genetic variation, alternative splicing, and prognosis. As for the m6A score and m6A gene signature, patients with low m6A scores exhibited an increased tumor mutation burden, immune activity, neoantigen load, and prolonged survival. A low m6A score indicated the potential for a low level of T-cell dysfunction, a considerably better treatment response, and durable clinical benefits from immunotherapy, bevacizumab and regorafenib. CONCLUSION: Glioma m6A clusters and gene signatures have distinctive TME features. The m6A gene signature may guide prognostic assessments and promote the use of effective strategies.

Polymeric micelles have opened up new horizons for improving drug delivery to brain particularly due to their small size, long circulation time, good stability and targetability. They are used to treat a variety of brain conditions, including glioblastoma, migraine, Alzheimer's, Parkinson's, and other conditions linked to the brain. Micelles are currently underutilised in brain targeting despite having several benefits and spanning a wide variety of brain illnesses. Since most medications are unable to cross the blood brain barrier, scientists are continuously working to discover efficient solutions to the problems. The most pressing issue was thought to be the viability and difficulties of translating micelles into the therapeutic setting. This review describes the role of micellar delivery system in brain diseases treatment along with their route of administration and outcomes. The review also discusses the current state of patents and clinical trials in the relevant fields and their potential future applications.

Edible mushrooms have been classified as "next-generation food" due to their high nutritional value coupled with their biological and functional potential. The most extensively studied and reported mushroom macromolecules are polysaccharides. However, macrofungi proteins and peptides are also a representative and significant bioactive group. Several factors such as species, substrate composition and harvest time significantly impact the mushroom protein content, typically ranging between 19 and 35% on a dry weight basis. Proteins work based on their shape and structure. Numerous extraction methods, including chemical and non-conventional, and their implications on protein yield and stability will be discussed. Beyond their biological potential, a great advantage of mushroom proteins is their uniqueness, as they often differ from animal, vegetable, and microbial proteins. According to recently published reports, the most relevant mushroom bioactive proteins and peptides include lectins, fungal immunomodulatory proteins, ubiquitin-like proteins, and proteins possessing enzymatic activity such as ribonucleases laccases, and other enzymes and ergothioneine. These are reported as antioxidant, antiviral, antifungal, antibacterial, antihypertensive, immunomodulatory, antitumour, antihypercholesterolemic or antihyperlipidemic, antidiabetic and anti-inflammatory properties, which improved proteins and peptides research interest and contributed to the increase of mushroom market value. This review provides an overview of the most relevant biochemical and biological properties of the main protein groups in edible mushrooms, explicitly focusing on their biomedical potential. Although mushrooms are a rich source of various proteins, many of these molecules have yet to be identified and characterised. Accordingly, it is crucial to identify and characterise new macromolecules of macrofungi origin, which opens an opportunity for further investigation to identify new bioactives for food, nutraceutical, or medicinal applications.

Myrtenol (C10H16O) is a volatile compound belonging to the terpenoid family of monocyclic monoterpenes. It is one of the essential oils constituents of several aromatic plants, including the genera Myrtus, Tanacetum, Artemisia, Hyssopus, and Rhodiola. The oxidation of α-pinene can produce it. Several reports demonstrated the pharmacological properties of myrtenol, including its antioxidant, antibacterial, antifungal, antidiabetic, anxiolytic, and gastroprotective activities. In this review, we discussed and highlighted in depth the pharmacological activities, cellular and molecular, providing insight into the mechanisms of myrtenol. In light of this finding, the interesting biological activities and abundance of myrtenol in nature suggest its potential applications in medicinal settings in the fight against various diseases.

BACKGROUND: The neurotransmitter metabolism in spontaneously hypertensive rats (SHR) is disordered, and these disturbances in neurotransmitter levels can further exacerbate the development of hypertension. Neurotransmitters can affect the expression of circadian clock genes. OBJECTIVE: To clarify the time-dependent internal mechanism of the imbalance of the target neurotransmitter metabolic rhythm of spontaneously hypertensive rats, the circadian research was carried out by the method of targeted metabolomics and molecular biology technology. METHODS: We have explored the mechanism of isorhynchophylline regulating the circadian rhythm through the ERK signaling pathway and thus treating hypertension by detecting the changes of central hypothalamic biological clock rhythm genes after isorhynchophylline intervention, from hypothalamic neurotransmitter rhythmicity. RESULTS: The expression of rhythm genes in normal rats showed a certain rhythm at 6 time points, while the expression of rhythm genes in model rats decreased, and the gene rhythm returned to normal after isorhynchophylline treatment. Cosine analysis of 12 neurotransmitters in hypothalamus showed that there were 6 rhythmic neurotransmitters in the normal group, while in the model group, 4 of the 6 neurotransmitters lost their rhythmicity, and the rhythmicity returned to normal after isorhynchophylline intervention. Compared with the normal group, the expression of ERK protein in the model group increased significantly and decreased after isorhynchophylline treatment. CONCLUSION: The mechanism of isorhynchophylline treating hypertension is not only the regulation of serum neurotransmitters rhythm, but also acting on rhythm genes in the feedback loop of the central biological clock.

In this review, the analysis of solid-solid phase transitions between crystalline polymorphs of organic molecules is discussed. Although active pharmaceutical ingredients (APIs) are the scope of the review, whether an organic molecule has a biological activity or not does not particularly define its interactions in the crystalline state. Therefore, other small organic molecules have been included in this analysis and in certain cases, polymers have been discussed too. The focus of the review is on experimental analysis; however, a section on computational and theoretical methods has been added because these methods are becoming important and are obviously helpful in understanding for example transition mechanisms because the results can be easily visualized. The following aspects of solid-solid phase transitions between crystalline structures are discussed. The thermodynamics of phase transitions between polymorphs involving thermodynamic equilibrium and the variables temperature and pressure closely linked to the Gibbs free energy are discussed. The two main transition mechanisms in the organic crystalline solid, displacive and concerted, are discussed. Experimental methods that are used to understand the mechanisms and thermodynamic equilibrium between different polymorphs of an API are reviewed. The switching of polymorph properties is discussed, and heat storage and release are reviewed as it is one of the main applications of solid-state phase transitions. Of interest for the control of drug products, constraining phase transitions have been reviewed, as they may help in increasing the bioavailability of an API by using metastable phases. Finally, second order phase transitions of organic materials, which appear to be rare, are discussed. It can be concluded that although the general theory of polymorphism and phase transitions is well understood, how it works out for a specific molecule remains difficult to predict.

About 2.8% of the global population are being suffered from Diabetes mellitus. Diabetes mellitus is a group of metabolic disorders that is characterized by an absolute lack of insulin and resulting in hyperglycemia. To overcome the challenges, many antidiabetic drugs are being used, and research is being carried out in search of more effective anti-diabetic drugs. To study the effectiveness of antidiabetic drugs, many diabetic models, chemicals, and diabetogenic hormones were used at the research level. In this review, we summarised various animal models used, chemicals that induce diabetes, their properties, and the mechanism of action of these models. Further, diabetes mellitus is generally induced in laboratory animals by several methods that include: chemical, surgical and genetic manipulations. To better understand both the pathogenesis and potential therapeutic agents, appropriate animal models of type 1 & type 2 diabetes mellitus are needed. However, for an animal model to have relevance to the study of diabetes, either the characteristics of the animal model should mirror the pathophysiology and natural history of diabetes or the model should develop complications of diabetes with an etiology similar to that of the human condition. There appears to be no single animal model that encompasses all of these characteristics, but there are many that provide very similar characteristics in one or more aspects of diabetes in humans. The use of the appropriate animal model based on these similarities can provide much-needed data on pathophysiological mechanisms operative in human diabetes.

BACKGROUND: Nitrogenous bisphosphonates (NBPs) are the major class of drugs that are used to treat osteoporosis. Recently, bisphosphonates (BPs) were reported to have an anticancer effect. These agents feature a high affinity that enables them to bind strongly to the human farnesyl pyrophosphate synthase enzyme. The correlation between this affinity and their anticancer effect was confirmed. OBJECTIVE: To date, the use of an oxygen atom as an isosteric replacement for the electronegative nitrogen atom in NBPs has not been reported, and its ability to retain the linker length and bisphosphonate pharmacophore remains unknown. The main aim of this work was to design some isosteric bisphosphonate analogs with oxygen atoms and evaluation of their binding affinity and anticancer activity. METHODS: The binding mode and stability of the designed compounds were achieved using human farnesyl pyrophosphate synthase (HFPPS) by docking and dynamic simulations. The compounds were synthesized, characterized, and screened for their anticancer activity against the breast cancer MCF-7 cell line and lung cancer A-549 cell line. The inhibitory activity of the tested compounds against HFPPS was evaluated. RESULTS: The compounds under investigation showed potential anticancer activity against the lung cell line with IC50 values of 41.7, 47.4, and 34.8 μg/ml in comparison to that of Risedronic acid (115 μg/ml). However, they do not exhibit potential activity against the breast cancer cell line. CONCLUSION: Compounds VII and VIII showed in vitro inhibition of human farnesyl pyrophosphate synthase with IC50 values of 82.2 and 98.8 μg/ml, respectively. Further optimization may be required in the future.

BACKGROUND: Use of antibiotics has dramatically eradicated bacterial infections in humans and animals. However, antibiotic overdose and abuse are responsible for the emergence of so-called multi-drug resistant bacteria. Interaction between antibiotics and gut microbiota: Gut microbiota deserves many functions in the host, and, among them, integrity of epithelial barrier and enhancement of protective immune responses are included. There is evidence that antibiotic treatment decreases the diversity of gut microbiota species, also provoking metabolic changes, increased susceptibility to colonization and decrease of antimicrobial peptide secretion, leading to antibiotic resistance. SPECIFIC AIMS: In this review the major mechanisms involved in antibiotic resistance will be illustrated. However, novel findings on the potential use of alternative treatments to overcome antibiotic resistance will be elucidated. In this regard, special emphasis will be placed on microcins, prebiotics, probiotics and postbiotics, as well as phage therapy and fecal microbial transplantation.

BACKGROUND: Angiopoietin-like protein 4 (Angptl4) is a glycoprotein that is involved in regulating lipid metabolism, which has been indicated as a link between hypertriglyceridemia and albuminuria in glomerulonephropathy. Deregulated lipid metabolism is increasingly recognized as an important risk factor of glomerulonephropathy. This study aimed to investigate the Angptl4 expression in renal tissue and podocyte under hyperlipidemia conditions and explore the potential molecular mechanisms. OBJECTIVE: The role of Angptl4 in hyperlipidemia-induced glomerular disease and the detailed underlying mechanisms are unclear. This study sought new insights into this issue. METHODS: We measured Angptl4 levels in the plasma and urine from patients with hyperlipidemia and healthy people. Rats were fed a high fat diet (HFD) to induce dyslipidemia model and the human podocytes were stimulated by palmitic acid as in vivo and in vitro experiments. The podocytes injury and the Angptl4 level in renal tissues were evaluated. Furthermore, the mechanism of Angptl4 on podocytes injury was investigated. RESULTS: The urinary Angptl4 level was gradually upregulated in both patients with hyperlipidaemia and high fat-diet-induced rats. HFD rats showed increased 24h-urinary protein and glomerular tuft area at week 12. The levels of nephrin and WT-1 were down-regulated, but the Angptl4 levels were markedly upregulated on the glomerular of rats on HFD. In the human podocytes, lipid accumulation accompanied by increases of Angptl4, but the expression of nephrin, WT-1, p-AMPKα and p-ACC was decreased after palmitic acid treatment. However, this injury effect was mediated by the aminoimidazole-4-carboxamide-1β-D-ribofuranoside (AICAR), activator of the low energy sensor AMPK/ACC signaling. CONCLUSION: This study was the first of its kind to show that podocyte damage induced by dyslipidemia could be associated with upregulated Angptl4 and that patients with hyperlipidemia might have relatively high urinary Angptl4 expression. The dysregulation of Angptl4 in the podocytes under hyperlipidemia is possibly carried out through AMPK/ACC signaling pathway.

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Currently, many therapeutic drugs are difficult to cross the blood-brain barrier (BBB), making it difficult to reach the site of action and thus fail to achieve the desired efficacy. In recent years, researchers and drug designers have increasingly focused on nanotechnology to break through the difficulty of small molecule inhibitors to cross the blood-brain barrier (BBB) and improve the success rate of drug delivery to the central nervous system. Among the common central neurological diseases, such as encephalitis, Parkinson's, Alzheimer's disease, and epilepsy, Alzheimer's disease has attracted much attention from researchers. Alzheimer's disease is a specific neurodegenerative disease, which causes irreversible degeneration of neurons as well as synapses in the brain, resulting in memory and cognitive dysfunction, along with other psychiatric symptoms and behavioral disorders, which seriously affects people's everyday life. Moreover, nanotechnology has excellent potential for application in AD treatment. Studies have shown that nanocarriers can target the delivery of chemotherapeutic drugs, antioxidants, and other therapeutic substances to brain tissue using existing physiological mechanisms, thus effectively alleviating the disease progression of AD. Therefore, various nanoparticles and nanomedicines have been developed and constructed for diagnosing and treating AD in the past decades, such as nanoparticles, bionanoparticles, liposomes, nano-gel, dendrimers, and self-assembled nanoparticles. This study aims to review the applications and results of nanotechnology in the treatment of Alzheimer's disease in recent years and provide some ideas and clues for future research and development of more effective drug delivery systems.

Hepatocellular carcinoma (HCC) is one of the foremost causes of tumor-affiliated demises globally. The HCC treatment has undergone numerous developments in terms of both drug and non-drug treatments. The United States Food and Drug Administration (FDA) has authorized the usage of a variety of drugs for the treatment of HCC in recent years, involving multi-kinase inhibitors (lenvatinib, regorafenib, ramucirumab, and cabozantinib), immune checkpoint inhibitors (ICIs) (pembrolizumab and nivolumab), and combination therapies like atezolizumab along with bevacizumab. There are currently over a thousand ongoing clinical and pre-clinical studies for novel HCC drugs, which portrays a competent setting in the field. This review discusses the FDA-approved HCC drugs, their molecular targets, safety profiles, and potential disadvantages; ii. The in-trial agents/drugs, their molecular targets, and possible benefits compared to alternatives, and iii-the current and future status of potential preclinical drugs with novel therapeutic targets for HCC. Consequently, existing drug treatments and novel strategies with their balanced consumption could ensure a promising future for a universal remedy of HCC in the near future.

BACKGROUND: Worldwide, type 2 diabetes mellitus (T2DM) is one of the most pervasive and fast-growing disorders, bringing long-term adverse effects. T2DM arises from pancreatic β-cells deficiency to produce enough insulin or when the body cannot effectively use the insulin produced by such cells. Accordingly, early diagnosis will decrease the long-term effects and high-healthcare costs of diabetes. OBJECTIVE: The objective is developing an integrated mathematical model of the insulin signaling network based on Brännmark's model, which can simulate the signaling events more comprehensively with the added key components. METHODS: In this study, a thorough mathematical model of the insulin signaling network was developed by expanding the previously validated model and incorporating the glycogen synthesis module. Parameters (69 parameters) of the integrated model were evaluated by a genetic algorithm by fitting the model predictions to eighty percent of experimental data from the literature. Twenty percent of the experimental data were used to evaluate the final optimized model. RESULTS: The time-response curves indicate that the GS phosphorylation reaches its maximum in response to 10-7 M insulin after 4 min, while the maximum phosphorylated GSK3 is attained within ~50 min. The dose-response curves for the GSP and GSK3 of the insulin signaling intermediaries in response to the increased concentration of insulin, after 10 min, in the input from 0-100 nM exhibits a decreasing trend, whereas an increasing trend was observed for the GS and GSK3P. The GSK and GS phosphorylation sensitivity was enhanced by increasing the initial insulin concentration level from 0.001 to 100 nM. However, the sensitivity of GSK3 to insulin concentration changes (from 0.001 to 100 nM) was 3-fold higher than GS sensitivity. CONCLUSION: Considerably, the trends of all signaling components simulated by the expanded model shows high compatibility with experimental data (R2 ≥ 0.9), which approves the accuracy of the proposed model. The proposed mathematical model can be used in many biological systems and combined with the whole-body model of the blood glucose regulation system for a better understanding of the causes and potential treatment of type 2 diabetes. Although, this model is not a complete description of insulin signaling, yet it can make profound contributions to improvements regarding other important components and signaling branches such as epidermal growth factor (EGF) signaling, as well as signaling in other cell types in the model structure of future works.

Stroke is currently one of the primary causes of morbidity and mortality worldwide. Unfortunately, the available treatments for stroke are still extremely limited. Indeed, stem cell (SC) therapy is a new option for the treatment of stroke that could significantly expand the therapeutic time window of stroke. Some proposed mechanisms for stroke-based SC therapy are the incorporation of SCs into the host brain to replace dead or damaged cells/tissues. Moreover, acute cell delivery can inhibit apoptosis and decrease lesion size, providing immunomudolatory and neuroprotection effects. However, several major SC problems related to SCs such as homing, viability, uncontrolled differentiation, and possible immune response, have limited SC therapy. A combination of SC therapy with nanoparticles (NPs) can be a solution to address these challenges. NPs have received considerable attention in regulating and controlling the behavior of SCs because of their unique physicochemical properties. By reviewing the pathophysiology of stroke and the therapeutic benefits of SCs and NPs, we hypothesize that combined therapy will offer a promising future in the field of stroke management. In this work, we discuss recent literature in SC research combined with NP-based strategies that may have a synergistic outcome after stroke incidence.

BACKGROUND: It has been reported that the consumption of antioxidant foods and beverages may benefit the development of cardiovascular risk factors. However, the impact of coffee consumption on some of these factors, such as homocysteine and leptin is controversial. Some clinical trials have suggested that coffee administration increases plasma total homocysteine levels, while others have found no significant changes in leptin concentrations. OBJECTIVE: This study aimed to assess the effects of coffee supplementation on homocysteine and leptin concentrations in a meta-analysis of clinical trials. METHOD: PubMed, Web of Science, Scopus, ClinicalTrials.gov, and Google Scholar databases were searched from inception to September 29, 2021. A fixed-effects model and the generic inverse variance weighting method were used for meta-analysis. RESULTS: The meta-analysis demonstrated that coffee administration significantly increases homocysteine levels (WMD: 0.55 µmol/L, 95% CI: 0.17, 0.93, p = 0.005, I2 = 0%) but has no significant changes in leptin concentrations (WMD: 1.34 ng/mL, 95% CI: -0.78, 3.45, p = 0.21, I2 = 0%). Additionally, the sensitivity analysis was robust for both homocysteine and leptin levels. CONCLUSION: The results of the present meta-analysis revealed that coffee supplementation raises serum homocysteine concentrations but has no effect on circulating leptin levels.

BACKGROUND: Percutaneous transluminal renal angioplasty (PTRA) with or without stenting is the gold standard therapy in patients with atherosclerotic renal artery stenosis (aRAS). However, therapeutic success depends on the correct timing of revascularization and the reversibility of the renal damage. MATERIALS AND METHODS: We report a case series of patients treated with PTRA for renovascular hypertension and ischemic nephropathy. We measured bilateral renal resistive index (RRI), circulating renal stem cells (RSC), and Neutrophil Gelatinase Associated Lipocalin (NGAL) at baseline and after PTRA at different time points to understand their changes in post-revascularization. RESULTS: At baseline, the studied patients (n=5) had different RSC levels. After PTRAs, all patients showed an improvement in blood pressure, while renal function varied differently within the studied subjects. RRI >0.75 at baseline and the absence of NGAL decrease after PTRAs were associated with post-PTRA renal function worsening, despite an increase of RSC in all patients. CONCLUSIONS: Although limited to a few patients, our observation allowed the exploration of the behaviour of the studied parameters in different degrees of renal ischemia. This revealed different disease models suggesting the importance of further investigations in larger and homogeneous cohorts to confirm that a greater basal RSC percentage, low RRI values before PTRA, and a post-revascularization NGAL reduction could be related to better renal outcomes in aRAS patients.

Cardiac involvement is the leading cause of death in patients with cardiac amyloidosis. Early recognition is crucial as it can significantly change the course of the disease. Until now, the imaging modality of choice for diagnosing cardiac amyloidosis has been cardiac magnetic resonance imaging (CMR) with late gadolinium enhancement (LGE). LGE-CMR in patients with cardiac amyloidosis reveals characteristic LGE patterns that lead to a diagnosis while also correlating well with disease prognosis. However, LGE-CMR has numerous drawbacks that the newer CMR modality, T1 mapping, aims to improve. T1 mapping can be further subdivided into native T1 mapping, which does not require the use of contrast, and ECV measurement, which requires the use of contrast. Numerous T1 mapping techniques have been developed, each one with its own advantages and disadvantages when it comes to procedure difficulty and image quality. A literature review to identify relevant published articles was performed by two authors. This review aimed to present the value of T1 mapping in diagnosing cardiac amyloidosis, quantifying the amyloid burden, and evaluating the prognosis of patients with amyloidosis with cardiac involvement.

Antibiotic resistance can be characterized, in biochemical terms, as an antibiotic's inability to reach its bacterial target at a concentration that was previously effective. Microbial resistance to different agents can be intrinsic or acquired. Intrinsic resistance occurs due to inherent functional or structural characteristics of the bacteria, such as antibiotic-inactivating enzymes, nonspecific efflux pumps, and permeability barriers. On the other hand, bacteria can acquire resistance mechanisms via horizontal gene transfer in mobile genetic elements such as plasmids. Acquired resistance mechanisms include another category of efflux pumps with more specific substrates, which are plasmid-encoded. Efflux pumps are considered one of the main mechanisms of bacterial resistance to antibiotics and biocides, presenting themselves as integral membrane transporters. They are essential in both bacterial physiology and defense and are responsible for exporting structurally diverse substrates, falling into the following main families: ATP-binding cassette (ABC), multidrug and toxic compound extrusion (MATE), major facilitator superfamily (MFS), small multidrug resistance (SMR) and resistance-nodulation-cell division (RND). The Efflux pumps NorA and Tet(K) of the MFS family, MepA of the MATE family, and MsrA of the ABC family are some examples of specific efflux pumps that act in the extrusion of antibiotics. In this review, we address bacterial efflux pump inhibitors (EPIs), including 1,8-naphthyridine sulfonamide derivatives, given the pre-existing knowledge about the chemical characteristics that favor their biological activity. The modification and emergence of resistance to new EPIs justify further research on this theme, aiming to develop efficient compounds for clinical use.

BACKGROUND: The soluble urokinase plasminogen activator receptor (suPAR), a biomarker of inflammation, has been found to be a potential prognostic factor of renal function progression. Our previous study showed that plasma suPAR levels were significantly associated with disease activity and prognosis in patients with antineutrophil cytoplasmic autoantibody-associated vasculitis (AAV). OBJECTIVE: This study aimed to explore whether urokinase plasminogen activator receptor (uPAR) participated in MPO-ANCA-induced glomerular endothelial cell (GEnC) injury, which is one of the most important aspects in the pathogenesis of AAV. METHODS: GEnC activation and injury were analyzed by measuring the mRNA levels of ICAM-1 and VCAM-1. Permeability experiments were performed to detect endothelial monolayer activation in number. The expression of TLR4 was detected. In addition, TLR4 siRNA and TLR4 inhibitors were employed to determine its role. Bioinformatics methods were used for further analysis. RESULTS: Compared with a single stimulation, uPAR could further increase the expression of ICAM-1 and VCAM-1 mRNA levels, increase endothelial monolayer permeability and impair tight junctions in GEnCs stimulated with MPO-ANCA-positive IgG. The expression of TLR4 was upregulated by uPAR and MPO-ANCA-positive IgG stimulation. TLR4 siRNA significantly reduced the expression of ICAM-1 and VCAM-1 mRNA levels induced by uPAR and MPO-ANCA-positive IgG. The TLR4 antagonist significantly downregulated the levels of ICAM-1 mRNA in cells and sICAM-1 in the supernatants of GEnCs treated with uPAR plus MPO-ANCA-positive IgG. PLAUR is a core gene in bioinformatics analysis. CONCLUSION: uPAR protein can enhance the GEnC activation and injury induced by MPO-ANCA-positive IgG through the TLR4 pathway, indicating that suPAR may be involved in the pathogenesis of AAV and that suPAR might be regarded as a potential therapeutic target.