Plasminogen Activator Activity Research Articles

PLAU, transcriptionally negatively regulated by GATA6, promotes lung squamous carcinoma cell proliferation and migration

BackgroundLung squamous cell carcinoma (LUSC) is associated with high mortality and has limited therapeutic treatment options. Plasminogen activator urokinase (PLAU) plays important roles in tumor cell malignancy. However, the oncogenic role of PLAU in the progression of LUSC remains unknown. GATA-binding factor 6 (GATA6), a key regulator of lung development, inhibits LUSC cell proliferation and migration, but the underlying regulatory mechanism remains to be further explored. Moreover, the regulatory effect of GATA6 on PLAU expression has not been reported. The aim of this study was to identify the role of PLAU and the transcriptional inhibition mechanism of GATA6 on PLAU expression in LUSC. MethodsTo identify the potential target genes regulated by GATA6, differentially expressed genes (DEGs) obtained from GEO datasets analysis and RNA-seq experiment were subjected to Venn analysis and correlation heatmap analysis. The transcriptional regulatory effects of GATA6 on PLAU expression were detected by real-time PCR, immunoblotting, and dual-luciferase reporter assays. The oncogenic effects of PLAU on LUSC cell proliferation and migration were evaluated by EdU incorporation, Matrigel 3D culture and Transwell assays. PLAU expression was detected in tissue microarray of LUSC via immunohistochemistry (IHC) assay. To determine prognostic factors for prognosis of LUSC patients, the clinicopathological characteristics and PLAU expression were subjected to univariate Cox regression analysis. ResultsPLAU overexpression promoted LUSC cell proliferation and migration. PLAU is overexpressed in LUSC tissues compared with normal tissues. Consistently, high PLAU expression, which acts as an independent risk factor, is associated with poor prognosis of LUSC patients. Furthermore, the expression of PLAU is transcriptionally regulated by GATA6. ConclusionIn this work, it was revealed that PLAU is a novel oncogene for LUSC and a new molecular regulatory mechanism of GATA6 in LUSC was unveiled. Targeting the GATA6/PLAU pathway might help in the development of novel therapeutic treatment strategies for LUSC.

Effect of plasminogen activator urokinase receptor gene on the activation and apoptosis of neutrophil

Objective: To investigate the effect of plasminogen activator urokinase receptor (PLAUR) gene on neutrophil activation and apoptosis in neutrophil-like cell model. Methods: Human acute myeloid leukemia cell line HL60 was cultured in vitro and induced to differentiate into neutrophil-like cells by all-trans retinoic acid (ATRA). Lentiviral vectors interfering with human PLAUR gene was constructed and transfected into neutrophil-like cells (siRNA group). The phosphate buffer saline (PBS) group (untransfected neutrophil-like cells) and normal blank control group (NC group) (neutrophil-like cells transfected with blank plasmid) were used as controls (n=3). After starvation culture and addition of interleukin-17 afterwards in these 3 groups, the expression of CD11b on the cell membrane was detected by flow cytometry, and the levels of myeloperoxide (MPO) and extracellular neutrophil traps (NETs) in the supernatant were detected by enzyme-linked immunosorbent assay (ELISA) to investigate the activation of neutrophil-like cells. The apoptosis was detected by flow cytometry with annexin V/propidium iodide (PI) double staining and the expressions of apoptosis-related proteins caspase-3, bax and bcl-2 were detected by Western blotting. Results: The expression of CD11b in siRNA group (32.37±8.17) was lower than that in PBS group (46.27±1.54) and NC group (53.07±8.14) (P<0.05) by flow cytometry. The levels of MPO and NETs (33.37±1.11, 57.69±3.03) in the supernatant of siRNA group were significantly lower than those in PBS group (41.64±2.20, 77.60±4.33) and NC group (40.84±5.11, 76.15±2.10) (P<0.05). Flow cytometry with annexin V/PI showed that the expression of apoptosis in siRNA group (20.42%±2.45%) was significantly higher than that in PBS group (11.91%±2.23%) and NC group (11.13%±2.56%) (P<0.05). The relative expression of caspase-3 protein and bax protein (0.84±0.05, 0.83±0.04) in siRNA group was significantly higher than that in PBS group (0.68±0.02, 0.63±0.08) and NC group (0.71±0.01, 0.66±0.10) (P<0.05), and the relative expression of anti-apoptosis protein bcl-2 decreased in siRNA group (0.38±0.02) than in PBS group (0.73±0.05) and NC group (0.69±0.06) (P<0.05). Conclusion: PLAUR promotes the activation of neutrophil-like cells and inhibits the apoptosis.

Plasminogen activator urokinase interacts with the fusion protein and antagonizes the growth of Peste des petits ruminants virus.

Peste des petits ruminants is an acute and highly contagious disease caused by the Peste des petits ruminants virus (PPRV). Host proteins play a crucial role in viral replication. However, the effect of fusion (F) protein-interacting partners on PPRV infection is poorly understood. In this study, we found that the expression of goat plasminogen activator urokinase (PLAU) gradually decreased in a time- and dose-dependent manner in PPRV-infected goat alveolar macrophages (GAMs). Goat PLAU was subsequently identified using co-immunoprecipitation and confocal microscopy as an F protein binding partner. The overexpression of goat PLAU inhibited PPRV growth and replication, whereas silencing goat PLAU promoted viral growth and replication. Additionally, we confirmed that goat PLAU interacted with a virus-induced signaling adapter (VISA) to antagonize F-mediated VISA degradation, increasing the production of type I interferon. We also found that goat PLAU reduced the inhibition of PPRV replication in VISA-knockdown GAMs. Our results show that the host protein PLAU inhibits the growth and replication of PPRV by VISA-triggering RIG-I-like receptors and provides insight into the host protein that antagonizes PPRV immunosuppression.IMPORTANCEThe role of host proteins that interact with Peste des petits ruminants virus (PPRV) fusion (F) protein in PPRV replication is poorly understood. This study confirmed that goat plasminogen activator urokinase (PLAU) interacts with the PPRV F protein. We further discovered that goat PLAU inhibited PPRV replication by enhancing virus-induced signaling adapter (VISA) expression and reducing the ability of the F protein to degrade VISA. These findings offer insights into host resistance to viral invasion and suggest new strategies and directions for developing PPR vaccines.

Effects of Ghrelin on Plasminogen Activator Activity in Human Umbilical Vein Endothelial Cells

Ghrelin and its growth hormone secretagogue receptor (GHSR) have been found in the placenta, both in endothelial and trophoblast cells. Ghrelin has been shown to decrease blood pressure in several systems and improve endothelial function by stimulating VEGF production. Because locally increased Ghrelin was detected in the preeclamptic fetoplacental unit, we hypothesized its involvement in the fibrinolysis and vascular tone typically observed in preeclamptic patients. This study aimed to evaluate the synthesis of plasminogen activators (PAs), PA inhibitor-1 (PAI-1), and urokinase-type PA (uPA) receptor (uPAR) in human umbilical vein endothelial cells (HUVECs) since the components of the PA/plasmin system are vital players in the extracellular matrix remodeling process necessary for angiogenesis. HUVECs were treated for 24 h with increasing concentrations of Ghrelin (10−11–10−7 M) or IL-1β (0.1 ng/mL). PAs, PAI-1, and uPAR mRNAs were determined by real-time PCR and PA activity was determined by casein underlay. We demonstrated an increase in uPA, tissue-type PA (tPA), and uPAR mRNA; a reduction in PAI-1 mRNA in HUVECs treated with Ghrelin; and an increase in total uPA activity. In conclusion, our results suggest a potential compensatory physiological mechanism for Ghrelin in response to the maternal endothelial dysfunction observed in the preeclamptic fetoplacental unit.

Extracellular vesicles from human urine-derived stem cells delay aging through the transfer of PLAU and TIMP1

Aging increases the risks of various diseases and the vulnerability to death. Cellular senescence is a hallmark of aging that contributes greatly to aging and aging-related diseases. This study demonstrates that extracellular vesicles from human urine-derived stem cells (USC-EVs) efficiently inhibit cellular senescence in vitro and in vivo. The intravenous injection of USC-EVs improves cognitive function, increases physical fitness and bone quality, and alleviates aging-related structural changes in different organs of senescence-accelerated mice and natural aging mice. The anti-aging effects of USC-EVs are not obviously affected by the USC donors’ ages, genders, or health status. Proteomic analysis reveals that USC-EVs are enriched with plasminogen activator urokinase (PLAU) and tissue inhibitor of metalloproteinases 1 (TIMP1). These two proteins contribute importantly to the anti-senescent effects of USC-EVs associated with the inhibition of matrix metalloproteinases, cyclin-dependent kinase inhibitor 2A (P16INK4a), and cyclin-dependent kinase inhibitor 1A (P21cip1). These findings suggest a great potential of autologous USC-EVs as a promising anti-aging agent by transferring PLAU and TIMP1 proteins.

The Effect of Parent-Teacher Associations Reviewed Policy Guidelines on the Status of Infrastructure in Ghana’s Rural basic Schools

This study looks at the adequacy of basic school infrastructure in the milieu of reviewed parent-teacher association policy guidelines in managing and administrating basic schools in Ghana. The study focused on nine deprived community basic schools in the Upper West region of Ghana. A purposive sampling technique was adopted to select the schools. The study adopted a qualitative approach, which encompassed the implementation of interviews, focus group discussions and observation. Findings from the study revealed that the review of the Parents-Teacher Association policy has decreased the rate at which parents assisted in the provision of infrastructure in many rural schools; pupils and teachers adopted their own ways of coping with the available limited infrastructure and most parents were no more willingly determined to support the schools with infrastructure. These were caused mainly by the following four components of the reviewed policy guidelines. Firstly, no student should be sent home, given any punishment or prevented from school activity for non-payment of PA levies or dues. Again, the school system should not be used for the purpose of collecting PA levies or dues. More so, PAs should liaise with Boards of Governors and Heads of Schools to determine projects to be undertaken in the schools based on the priority needs of the schools. Lastly, heads/teachers of schools are not required to be signatories and front liners to PA activities and accounts unless so decided by PAs themselves. The study suggests that PTA members should be given much education on educational policies. They should be consulted in the formulation of educational policies. Finally, there should be existence of clear public regulations and measures that will motivate and explicitly indicate the roles of PA’s in the provision of basic school infrastructure. These will further prompt their willingness to assist basic schools with infrastructure.

Fibrin and Fibrinolytic Enzyme Cascade in Thrombosis: Unravelling the Role.

Blood clot formation in blood vessels (thrombosis) is a major cause of life-threatening cardiovascular diseases. These clots are formed by αA-, βB-, and ϒ-peptide chains of fibrinogen joined together by isopeptide bonds with the help of blood coagulation factor XIIIa. These clot structures are altered by various factors such as thrombin, platelets, transglutaminase, DNA, histones, and red blood cells. Various factors are used to dissolve the blood clot, such as anticoagulant agents, antiplatelets drugs, fibrinolytic enzymes, and surgical operations. Fibrinolytic enzymes are produced by microorganisms (bacteria, fungi, etc.): streptokinase of Streptococcus hemolyticus, nattokinase of Bacillus subtilis YF 38, bafibrinase of Bacillus sp. AS-S20-I, longolytin of Arthrobotrys longa, versiase of Aspergillus versicolor ZLH-1, etc. They act as a thrombolytic agent by either enhancing the production of plasminogen activators (tissue or urokinase types), which convert inactive plasminogen to active plasmin, or acting as plasmin-like proteins themselves, forming fibrin degradation products which cause normal blood flow again in blood vessels. Fibrinolytic enzymes may be classified in two groups, as serine proteases and metalloproteases, based on their catalytic properties, consisting of a catalytic triad responsible for their fibrinolytic activity having different physiochemical properties (such as molecular weight, pH, and temperature). The analysis of fibrinolysis helps to detect hyperfibrinolysis (menorrhagia, renal failure, etc.) and hypofibrinolysis (diabetes, obesity, etc.) with the help of various fibrinolytic assays such as a fibrin plate assay, fibrin microplate assay, the viscoelastic method, etc. These fibrinolytic activities serve as a key aspect in the recognition of numerous cardiovascular diseases and can be easily produced on a large scale with a short generation time by microbes and are less expensive.

Ligneous periodontitis exacerbated by Behçet’s disease in a patient with plasminogen deficiency and a stop-gained variant PLG c.1468C > T: a case report

BackgroundPlasminogen serves as the precursor to plasmin, an essential element in the fibrinolytic process, and is synthesized primarily in the liver. Plasminogen activation occurs through the action of plasminogen activator, converting it into plasmin. This conversion greatly enhances the fibrinolytic system within tissues and blood vessels, facilitating the dissolution of fibrin clots. Consequently, congenital deficiency of plasminogen results in impaired fibrin degradation. Patients with plasminogen deficiency typically exhibit fibrin deposits in various mucosal sites throughout the body, including the oral cavity, eyes, vagina, and digestive organs. Behcet's disease is a chronic recurrent systemic inflammatory disease with four main symptoms: aphthous ulcers of the oral mucosa, vulvar ulcers, skin symptoms, and eye symptoms, and has been reported worldwide. This disease is highly prevalent around the Silk Road from the Mediterranean to East Asia.We report a case of periodontitis in a patient with these two rare diseases that worsened quickly, leading to alveolar bone destruction. Genetic testing revealed a novel variant characterized by a stop-gain mutation, which may be a previously unidentified etiologic gene associated with decreased plasminogen activity.Case presentationThis case report depicts a patient diagnosed with ligneous gingivitis during childhood, originating from plasminogen deficiency and progressing to periodontitis. Genetic testing revealed a suspected association with the PLG c.1468C > T (p.Arg490*) stop-gain mutation. The patient's periodontal condition remained stable with brief intervals of supportive periodontal therapy. However, the emergence of Behçet's disease induced acute systemic inflammation, necessitating hospitalization and treatment with steroids. During hospitalization, the dental approach focused on maintaining oral hygiene and alleviating contact-related pain. The patient's overall health improved with inpatient care and the periodontal tissues deteriorated.ConclusionsCollaborative efforts between medical and dental professionals are paramount in comprehensively evaluating and treating patients with intricate complications from rare diseases. Furthermore, the PLG c.1468C > T (p.Arg490*) stop-gain mutation could contribute to the association between plasminogen deficiency and related conditions.

A Machine Learning Approach for Physical Activity Recognition in Cystic Fibrosis

ABSTRACT This study aimed to develop and validate machine learning models to predict intensities in children and adolescents with cystic fibrosis (CF) across different accelerometry brands and placements. Thirty-five children and adolescents with CF (11.6 ± 2.8 yrs; 15 girls) and 28 healthy youth (12.2 ± 2.7 yrs; 16 girls) performed six activities whilst wearing GENEActivs (both wrists) and ActiGraphs GT9X (both wrists and waist). Three supervised learning classifiers (K-Nearest Neighbour, Random Forest and eXtreme Gradient Boosted Decision Tree) were used to identify the input signal pattern for each PA type and intensity, with a 10-fold cross-validation utilized to assess the performance of the classifiers. ActiGraph GT9X on the dominant wrist and waist and GENEActiv on the dominant wrist failed to predict vigorous intensity PA activities. All other models, for activity type and intensities, exceeded 97% accuracy, with a sensitivity and specificity of greater than 95%, irrespective of accelerometer brand, placement or health condition.

Plasminogen activator urokinase receptor as a diagnostic and prognostic biomarker in type 2 diabetic patients with cardiovascular disease.

Cardiovascular diseases are the main cause of death among type 2 diabetic patients. Higher levels of plasminogen activator urokinase receptor have been found to predict morbidity and mortality across acute and chronic diseases in the common populace. This study aims to explore the role of serum plasminogen activator urokinase receptor levels as a cardiometabolic risk factor among type 2 diabetic Iraqi patients. Seventy type 2 diabetic patients (40 male and 30 female) (mean age: 46.20±7.56 years) participated in this study; 35 patients were with cardiovascular disease and 35 were without cardiovascular disease; their ages range was 40-55 years. In addition, 30 individuals who apparently healthy were selected as the control group. There were significant increases (P<0.05) in glycemic and lipid profiles in diabetic patients with cardiovascular disease as compared to those without cardiovascular disease and control group. The present results reveal high levels of plasminogen activator urokinase receptor (2500.72±12.36 ρg/mL versus 2255.32±10.15 ρg/mL) with OR=1.80, 95%CI 1.2, and P=0.0001 in type 2 diabetic patients with and without cardiovascular disease respectively as compared to healthy control (229.00±14.48 ρg/mL). It has been concluded that serum plasminogen activator urokinase receptor showed higher levels among type 2 diabetic patients with cardiovascular disease, this revealed it's critical role in cardiac disease. Therefore, it could be considered a more sensitive biomarker for the detection of cardiovascular events among type 2 diabetic patients who were at high-risk.

Urokinase-type Plasminogen Activator-induced Mouse Back Pain Model.

A model of persisting lower back pain can be induced in mice with the simple methodology described herein. Step-by-step methods for simple, rapid induction of a persisting back pain model in mice are provided here using an injection of urokinase-type plasminogen activator (urokinase), a serine protease present in humans and other animals. The methodology for induction of persisting lower back pain in mice involves a simple injection of urokinase along the ligamentous insertion region of the lumbar spine. The urokinase inflammatory agent activates plasminogen to plasmin. Typically, the model can be induced within 10 min and hypersensitivity persists for at least 8 weeks. Hypersensitivity, gait disturbance, and other standard anxiety- and depression-like measures can be tested in the persisting model.Back pain is the most prevalent type of pain. To improve awareness of back pain, the International Association for the Study of Pain (IASP) named 2021 the "Global Year about Back Pain" and 2022 the "Global Year for Translating Pain Knowledge to Practice." One limitation of the therapeutic advancement of pain therapeutics is the lack of suitable models for testing persistent and chronic pain. Thefeatures of this modelare suitable for testing potential therapeutics aimed at the reduction of back pain and its ancillary characteristics, contributing to IASP's naming 2022 as the Global Year for Translating Pain Knowledge to Practice.

Dietary probiotic Aspergillus niger preparation improves the growth performance, health status, and gut microbiota of white shrimp, Penaeus vannamei

Aspergillus niger is a unique fungus with benefits that can help improve the performance of terrestrial and aquatic animals. However, studies on the use of A. niger on aquatic animal species are limited. The present study investigated the effects of A. niger preparation as a dietary supplement on growth, gut microbiota, and immune response of white shrimp, Penaeus vannamei. The experiment was conducted over a 56-day trial period, with shrimps fed a control diet, and three diets containing three doses of A. niger preparation 0.5, 1 and 1.5 g (kg diet)−1) designated as P500, P1000 and P1500, respectively. The results showed that increasing concentrations of A. niger preparation led to higher weight gain and final weight in shrimp. Moreover, increasing levels of A. niger preparation of P1000 and P1500 reduced the mortality rate of shrimp challenged with Vibrio parahaemolyticus. In A. niger groups, PA, RBs, PO and LYS activities of shrimp significantly increased compared to the control group. Microbial analysis revealed significantly higher Vibrio-like counts in the gut of shrimp fed the control diet than in all A. niger-supplemented diets. Shewanella belonging to the dominant phylum Proteobacteria was highly expressed in the microbiota of shrimp fed P1000 diet. Meanwhile, Vibrio was relatively abundant in the control group. Unique genera, such as JGI0000069P2 and Marinicella, promoted bioremediation activities, while Halobacteriovorax aided in the elimination of V. parahaemolyticus infection in shrimp. Notably, a symbiotic relationship between Shewanella and Halobacteriovorax bacteria in the gut jointly boosted the immune responses of shrimp in defense against V. parahaemolyticus infection. These findings suggest that the A. niger preparation, due to its beneficial effects, could potentially be included in the diet to promote growth and a healthy intestinal microbiota, while also serving as a prophylactic treatment and immunological booster for shrimp.

The role of plasminogen and urokinase activator of plasminogen in the treatment of endogenous uveitis in children

AIM: To determine the content of plasminogen and urokinase activator of plasminogen in tears and blood serum and to identify correlations between the studied parameters and the clinical picture of uveitis.&#x0D; MATERIAL AND METHODS: One hundred thirty-three eyes with uveitis were examined in 74 patients aged 3 to 17 yr (average 10.453.35 yr). The content of the urokinase activator of plasminogen (UPA) was studied in 188 tear samples and 22 blood serum samples. The dynamics of UPA in tears were studied in 28 patients (51 eyes). The plasminogen content of 86 tear samples and 34 blood serum samples was studied. The dynamics of plasminogen in tears were studied in five patients (nine eyes). The concentrations of UPA and plasminogen were measured using the ELISA method and the kits ELISA kit for plasminogen activator, urokinase (UPA)/ELISA Kit for Plasminogen, Cloud-Clone Corp., USA).&#x0D; RESULTS: An increase in the content of UPA in the tears of children with uveitis was associated with higher inflammatory activity (p=0.04). An increase in the content of UPA in tears was associated with an increase in the degree of proliferative changes (p=0.04). An increase in the content of UPA and plasminogen in tears was found 12 months after surgery. There was an increase in the content of UPA (p=0.0001) and plasminogen in tears (p=0.009) and blood serum (p=0.09) with age.&#x0D; CONCLUSION: The content of UPA in tears increased significantly when severe uveitis was compared with inactive uveitis. An increase in the content of UPA in tears was associated with an increase in the degree of proliferative changes, which reflects the severity of the uveitis course. The content of UPA and plasminogen in tears and blood serum increased with age. An increase in UPA and plasminogen was observed within 12 months after surgery, with both returning to preoperative values by the third month of the postoperative period, which reflects the normal course of the wound healing process.

The role of neutrophils in corneal nerve regeneration

BackgroundTo investigate the role of neutrophils in corneal nerve regeneration.MethodsA mouse model simulating corneal nerve injury was established and samples from corneal scraping with and without neutrophil closure were collected. These samples were used for corneal nerve staining, ribonucleic acid sequencing, and bioinformatics. Differential expression analysis was used to perform enrichment analysis to identify any significant differences between these two groups. The differential genes were then intersected with neutrophil-associated genes and a protein-protein interaction network was constructed using the intersected genes. The immune infiltration between the two groups was examined along with the immune cell variation between the high and low gene expression groups.ResultsNeutrophil removal delays corneal epithelial and nerve regeneration. A total of 546 differential genes and 980 neutrophil-associated genes, with 27 genes common to both sets were obtained. Molecular Complex Detection analysis yielded five key genes, namely integrin subunit beta 2 (ITGB2), matrix metallopeptidase 9 (MMP9), epidermal growth factor (EGF), serpin family E member 1 (SERPINE1), and plasminogen activator urokinase receptor (PLAUR). Among these genes, ITGB2, SERPINE1, and PLAUR exhibited increased expression in the neutrophil-confined group, while MMP9 and EGF showed decreased expression, with MMP9 and EGF displaying a more significant difference. Immune infiltration was also observed between the two groups, revealing significant differences in the infiltration of M0 macrophages, activated mast cells, and neutrophils. Moreover, the neutrophil levels were lower in the groups with low MMP9 and EGF expressions and higher in the high-expression group.ConclusionNeutrophil confinement might significantly affect the MMP9 and EGF expression levels. Strategies to inhibit MMP9 could potentially yield therapeutic benefits.

γ-Bungarotoxin impairs the vascular endothelial barrier function by inhibiting integrin α5

γ-bungarotoxin (γ-BGT) is an RGD motif-containing protein, derived from the venom of Bungarus multicinctus, leading to acute death in mice. These RGD motif-containing proteins from snake venom belonging to the disintegrin family can interfere with vascular endothelial homeostasis by directly binding cell surface integrins. Targeting integrins that generate vascular endothelial dysfunction may contribute to γ-BGT poisoning, however, the underlying mechanisms have not been investigated in detail. In this study, the results showed that γ-BGT played a role in -promoting the permeability of the vascular endothelial barrier. Depending on its selective binding to integrin α5 in vascular endothelium (VE), γ-BGT initiated downstream events, including focal adhesion kinase dephosphorylation and cytoskeleton remodeling, resulting in the intercellular junction interruption. Those alternations facilitated paracellular permeability of VE and barrier dysfunction. Proteomics profiling identified that as a downstream effector of the integrin α5 / FAK signaling pathway cyclin D1 partially mediated the cellular structural changes and barrier dysfunction. Furthermore, VE-released plasminogen activator urokinase and platelet-derived growth factor D could serve as potential diagnostic biomarkers for γ-BGT-induced vascular endothelial dysfunction. Our results indicate the mechanisms through which γ-BGT as a novel disintegrin directly interacts with the VE, with consequences for barrier dysfunction.

Mecanismos de virulência de Enterococcus faecalis associados ao câncer colorretal

Introduction: Colorectal cancer (CRC) is one of the most prevalent in the number of cases and deaths in the world. The intestinal microbiota performs several functions in the human host, and can directly influence health, affecting metabolism, the immune system and the production of hormones. Studies show that dysregulated intestinal microbiota or dysbiosis associated with virulence mechanisms may be related to the appearance of CRC. Among the microorganisms that make up the intestinal microbiota, the Enterococcus faecalis stands out. This Gram-positive bacterium is commensal of the gastrointestinal tract; however, it can act as an opportunistic pathogen, through the mechanisms associated with virulence. Objective: The aim of this literature review was to describe the role of virulence mechanisms of E. faecalis associated with CRC. Material and Methods: Literature review of articles published in the ScienceDirect and PubMed databases in the last 20 years (2002–2022), using the keywords Enterococcus, faecalis and colorectal cancer. Results: Of a total of 313 articles found, 39 were included for the development of this bibliographic review. The virulence mechanisms of the E. faecalis most pointed out in the literature associated with CRC are reactive oxygen species (58.9%), genomic instability (46.1%), 4-hydroxy-2-nonenal (15.4%), gelatinase (12.8%), lipoteichoic acid (10.2%), aggregating substance (10.2%), toll-like receptors (7.7%), plasminogen activator urokinase (2.56%) and phosphotransferase system (2.56%). Conclusions: It was possible to verify that some mechanisms described in E. faecalis, mainly the reactive oxygen species, might be associated with the development of CRC.

A deficient immune response to SARS-CoV-2 in the nasopharynx is associated with severe COVID-19 pneumonia

ObjectivesWe analyzed the expression of inflammatory and antiviral genes in the nasopharynx of SARS-CoV-2 infected patients and their association with the severity of COVID-19 pneumonia. MethodsWe conducted a cross-sectional study on 223 SARS-CoV-2 infected patients. Clinical data were collected from medical records, and nasopharyngeal samples were collected in the first 24 hours after admission to the emergency room. The gene expression of eight proinflammatory/antiviral genes (plasminogen activator urokinase receptor [PLAUR], interleukin [IL]-6, IL-8, interferon [IFN]-β, IFN-stimulated gene 15 [ISG15], retinoic acid-inducible gene I [RIG-I], C-C motif ligand 5 [CCL5], and chemokine C-X-C motif ligand 10 [CXCL10]) were quantified by real-time polymerase chain reaction. Outcome variables were: (i) pneumonia; (ii) severe pneumonia or acute respiratory distress syndrome. Statistical analysis was performed using multivariate logistic regression analyses. ResultsWe enrolled 84 mild, 88 moderate, and 51 severe/critical cases. High expression of PLAUR (adjusted odds ratio [aOR] = 1.25; P = 0.032, risk factor) and low expression of CXCL10 (aOR = 0.89; P = 0.048, protective factor) were associated with pneumonia. Furthermore, lower values of ISG15 (aOR = 0.88, P = 0.021), RIG-I (aOR = 0.87, P = 0.034), CCL5 (aOR = 0.73, P <0.001), and CXCL10 (aOR = 0.84, P = 0.002) were risk factors for severe pneumonia/acute respiratory distress syndrome. ConclusionAn unbalanced early innate immune response to SARS-CoV-2 in the nasopharynx, characterized by high expression of PLAUR and low expression of antiviral genes (ISG15 and RIG-I), and chemokines (CCL5 and CXCL10), was associated with COVID-19 severity.

Effect of urokinase-type plasminogen activator combined with clinical stage and Barcelona Clinic Liver Cancer stage on the prognosis of patients with hepatocellular carcinoma.

The aim of this investigation is to evaluate the association and potential mechanism between plasminogen activator urokinase (PLAU) and the prognosis of patients with liver hepatocellular carcinoma (LIHC). We verified PLAU expression and its correlation with LIHC patients' prognosis in The Cancer Genome Atlas (TCGA) database. The interaction network for protein-gene was established in the GeneMania database and the STRING database, and the association between PLAU and immune cells was assessed in Tumor Immune Estimation Resource (TIMER) and TCGA databases. The potential physiological mechanism was elucidated by the Gene Set Enrichment Analysis (GSEA) enrichment assessment. Finally, the individual clinical data of 100 LIHC patients were retrospectively evaluated to further analyze the clinical value of PLAU. The PLAU expression in LIHC tissues was greater than in paracancerous tissues, and LIHC patients with low PLAU expression had better disease-specific survival (DSS), overall survival (OS), and progression free interval (PFI) than those with high PLAU expression. In the TIMER database, the PLAU expression was positively associated with six kinds of infiltrating immune cells: CD4+ T, neutrophils, CD8+ T, macrophages, B, and dendritic cells, while GSEA enrichment analysis indicated PLAU may impact the biological activities of LIHC by taking part in MAPK and JAK_STAT signaling pathways, angiogenesis, and P53. There were statistically significant differences in T-stage and Edmondson grading between the two groups of patients with high and low expression of PLAU (P<0.05). The tumor progression rates were 88% (44/50) and 92% (46/50) respectively in the low and high PLAU groups, with early recurrence rates of 60% (30/50) and 72% (36/50), and median PFS of 29.5 and 23 months, respectively. The COX regression analysis showed PLAU expression and CS and Barcelona Clinic Liver Cancer (BCLC) stages were independent prognostic factors affecting tumor progression in LIHC patients. The decreased expression of PLAU can prolong the DSS, OS, and PFI in LIHC patients, and can be utilized as a novel predictive index. PLAU combined with CS staging and BCLC staging has good clinical value in the early screening and prognosis of LIHC. These results reveal an efficient approach for developing anticancer strategies against LIHC.

Screening of proteases produced by Aspergillus micromycetes active against proteins of the hemostasis system.

For these intents, proteases cardiovascular disease is the primary cause of death; hence, accurate diagnosis and treatment are urgently required are regarded as prospective agents . High substrate specificity is needed for an effective enzyme, which makes Aspergillus micromycetes, known for producing proteases with precise action, biotechnologically promising. This study mainly aimed to look at the possibilities of Aspergillus species, which had never been mentioned in terms of general proteolytics. Every species was cultivated in two-stage submerged conditions with two different nitrogen sources; whereupon, proteolytic activity in culture fluid was determined. Chromogenic peptide substrates and fibrin plates were used to evaluate the thrombin, plasmin, factor Xa, urokinase, protein C-like, activating activities towards hemostasis proteins, as well as fibrinolytic and plasminogen-activating activities of these species. It was found that A. aureolatus and A. tennesseensis are active proteolytics exhibiting plasmin-like activities (116.17 and 87.09 U×10-3, respectively), factor Xa-like activity (76.27 and 77.92 U×10-3, respectively) and urokinase activity (85.99 and 59.91 U×10-3, respectively). The thrombin-like activity was found for A. tabacinus (50.37 U×10-3), and protein C-like activity was noticeable for A. creber, A. jensenii, A. protuberus, and A. ruber (62.90, 65.51, 73.37, and 111.85 U×10-3, respectively). Additionally, more than half of species had the ability to directly activate plasminogen or operate as fibrinolytics. New proteolytic strains were discovered, offering hope for the therapy of cardiovascular disorders. The high specificity and activity of fungal enzymes make them useful in a variety of fields, including medicine and diagnostics.

Effects of CeO2 Nanomaterial on Pseudomonas Aeruginosa Mediated Bronchiectasis Inflammation Response

There are many researches on the preparation of rare earth metals (REM) materials and bactericidal materials, but there are few researches on the preparation of REM oxides based on the laser evaporation (LE) method in the field of bactericidal. In this research, ZnO–CeO2 nanoparticles (NPs) were obtained by the LE method with 100 W single-mode CW CO2 laser as the light source and cerous carbonate and zinc acetate as the target materials. While physical characterization of the ZnO–CeO2 NPs, Staphylococcus aureus (SA), Bacillus subtilis var niger (BSVN), and pseudomonas aeruginosa (PAE) were undertaken as test objects to verify the bactericidal performance of the nanomaterial. A PAE mediated inflammation model of bronchiectasis rats was established, and 40 SD rats were screened and rolled into 4 groups: a control (Ctrl) group, a sham group, a model group without nano solution injection (Model group), and a model group injected with nano solution (Model +NPs group). The effects of nanomaterials on inflammation were analyzed. The results suggested that ZnO–CeO2 NPs were scattered rod particles with uniform morphological distribution. XRD tests revealed that with the increase of ZnO content, its characteristic peaks in the NPs also increased. The preparation of NPs exhibited good bactericidal performance against SA and BSVN, and increasing the concentration of NPs greatly inhibited the activity of PA. By comparing with the model group, the upregulated IL-17 and IL-6 were inhibited (P &lt;0.01), while the downregulated IL-10 and TGF-β were reversed (P &lt;0.01). It meant that the NPs alleviated the inflammation of bronchiectasis mediated by PA, and thus improved the lung function damaged by inflammation.