Biomarkers of inflammation and metabolic disorders and ultrasound findings of subclinical atherosclerosis in patients with psoriasis

Psorijaza pogađa 2-3% svetske populacije i kao sistemsko hronično zapaljensko oboljenje praćena je brojnim komorbiditetima koji utiču i na preživljavanje bolesnika. Oboleli od psorijaze imaju kraći životni vek usled povećanog rizika od kardiovaskularnih oboljenja, šećerne bolesti i metaboličkog sindroma. Istraživanje je dizajnirano kao prospektivna studija preseka kojom su upoređivani testirani parametri u grupi obolelih od psorijaze (66 ispitanika) i kontrolnim grupama obolelih od ekcema (20 ispitanika) i zdravih kontrola (20 ispitanika). Isključeni su oboleli od psorijaze i ekcema sa ranije dijagnostikovanim ili aktuelnim kardiovaskularnim, metaboličkim ili drugim sistemskim bolestima, takođe ni bolesnici lečeni sistemskom terapijom. Svi ispitanici bili su između 18 i 60 godina života. Ispitivani su antropomentrijski, epidemiološki i klinički podaci, laboratorijski parametri inflamacije, hiperkoagulabilnosti, kardiovaskularnog rizika, lipidnog statusa, metabolizma glukoze, parametri bubrežne funkcije, ultrasonografski prediktori subkliničke ateroskleroze na perifernim arterijama i srcu. Rezultati su diskutovani u svetlu različitih, podataka o vezi psorijaze i ekcema sa aterosklerozom i ostalim kardiometaboličkim stanjima. Rezultati istraživanja su sadržani u sledećim zaključcima: 1. Rani ultrasonografski prediktori za razvoj subkliničke ateroskleroze predstavljeni debljinom intime medije karotidne i femoralne arterije su u korelaciji sa psorijazom, ali ne sa ekcemom. Psorijaza predstavlja nezavisan faktor rizika za razvoj subkliničke ateroskleroze na osnovu multivarijantne analize, jer najvažniji prediktor za debljinu intime medije karotidne i femoralne arterije predstavlja psorijaza sama po sebi. 3. Povećane koncentracije biomarkera inflamacije i metaboličkih poremećaja su u korelaciji sa psorijazom, ali ne sa ekcemom. 4. Veća je učestalost metaboličkog sindroma kod obolelih od psorijaze u odnosu na kontrolne grupe. 5. Postoji pozitivna korelacija između stepena aktivnosti psorijaze izražene PASI skorom sa koncentracijom biomarkera inflamacije i metaboličkih poremećaja i ehokardiografskim prediktorima, ali ne i sa ultrasonografskim znacima rane ateroskleroze na perifernim i renalnim arterijama. 6. Smanjena brzina protoka u brahijalnoj arteriji kod obolelih od psorijaze ukazuje na mogućnost povećanog rizika za nastanak koronarne bolesti. 7. Ehokardiografski prediktori za razvoj srčane disfunkcije nađeni su kod obolelih od psorijaze u većoj učestalosti u odnosu na kontrolne grupe. Psorijaza je u korelaciji sa povećanim koncentracijama biomarkera inflamacije i metaboličkih poremećaja, te doprinosi razvoju sistemske ateroskleroze, kao i nastanku kardiovaskularnih i metaboličkih oboljenja i nameće potrebu za identifikacijom obolelih sa ovim rizicima.Psoriasis affects 2-3% of the world's population and as a systemic chronic inflammatory disease is associated with many comorbidities that affects on the survival of patients. People with psoriasis have a shorter life expectancy due to increased risk of cardiovascular disease, diabetes and metabolic syndrome. The study was designed as a prospective cross-sectional study that tested parameters were compared in a group of psoriasis patients (66 subjects) and control groups of patients with eczema (20 subjects) and healthy controls (20 subjects). Excluded are suffering from psoriasis and eczema with previously diagnosed or current cardiovascular, metabolic or other systemic diseases, and neither do patients treated with systemic therapy. All subjects were between 18 and 60 years of age. They were evaluated for antropometric, epidemiological and clinical data, laboratory parameters of inflammation, hypercoagulability, cardiovascular risk, lipid status, metabolism of glucose, the parameters of renal function, ultrasonography predictors of subclinical atherosclerosis in peripheral arteries and heart. The results are discussed in the light of various data regarding psoriasis and eczema with atherosclerosis and other cardiometabolic conditions. The research results are contained in the following conclusions: 1. Early ultrasonographic predictors for the development of subclinical atherosclerosis represented intima media thickness of the carotid and femoral artery correlated with psoriasis, but not with eczema. Psoriasis is an independent risk factor for the development of subclinical atherosclerosis based on multivariate analysis, because the most important predictor of intima media thickness of the carotid and femoral artery represents psoriasis itself. 3. Increased concentrations of biomarkers of inflammation and metabolic disorders correlated with psoriasis, but not with eczema. 4. Increased frequency of the metabolic syndrome in psoriasis patients as compared to control groups. 5. There is a positive correlation between level of psoriasis activity expressed in PASI score and serum biomarkers of inflammation and metabolic disorders, and echocardiographic predictors, but not with ultrasonographic signs of early atherosclerosis on peripheral and renal arteries. 6. The reduced flow in the brachial artery in patients with psoriasis indicates the possibility of an increased risk for coronary artery disease. 7. Echocardiographic predictors for developement of cardiac dysfunction have been found more frequently in patients suffering from psoriasis compared to the control groups. Psoriasis is correlated with increased concentrations of biomarkers of inflammation and metabolic disorders, and to contribute to the development of systemic atherosclerosis, which all together represent predictors of cardiovascular and metabolic diseases and imposes the need for identification of patients with these risks

Influence of bioactive molecules of lactobacilli on autophagy and inflamation processes in in vitro and in vivo systems

Izolacija i karakterizacija bakterijskih biomolekula koji interaguju sa receptorima ćelija domaćina predstavlja kljuĉ za razumevanje mehanizama probiotiĉkog dejstva laktobacila. Savremena istraţivanja probiotiĉkih bakterija usmerena su ka identifikaciji biomolekula koji mogu modulisati razliĉite signalne puteve u humanim ćelijama. Svi molekuli koji su poreklom iz probiotika i odgovorni su za njihov pozitivan efekat na zdravlje domaćina nazvani su postbiotici. Zbog slabijeg imunostimulišućeg potencijala, njihova primena predstavlja bezbednu alternativu primeni ţivih bakterija. Ovo istraţivanje je imalo za cilj da testira mogućnost primene postbiotika u ublaţavanju simptoma bola i neţeljenih efekata koji nastaju kao posledica primene analgetika. Taĉnije, definisana su dva specifiĉna cilja istraţivanja: (i) ispitati uticaj bioaktivnih molekula odabranih sojeva laktobacila na proces autofagije u hepatocitima in vitro, kao i protektivan efekat ovih molekula kod toksiĉnosti izazvane paracetamolom i (ii) ispitati potencijalni imunomodulatorni efekat egzopolisaharida (EPS-CG11) izolovanog iz soja Lactobacillus paraplantarum BGCG11, u in vivo eksperimentalnim modelima inflamacije. Eksperimenti u kulturi hepatocita ukljuĉili su praćenje stepena oštećenja HepG2 ćelija izloţenih toksiĉnoj koncentraciji paracetamola i procesa autofagije, sa ciljem identifikacije potencijalnog mehanizma delovanja postbiotika. Metodološki, vijabilnost HepG2 ćelija analizirana je MTT i LDH esejima. Autofagija je praćena Western blot analizom odreĊivanjem ekspresije p62/SQSTM1 proteina i akumulacijom liposolubilne forme LC3 proteina. Dodatno, autofagija je analizirana praćenjem ekspresije BECN1, Atg5, p62/SQSTM1 i PINK1 gena i autofagnog fluksa. Za analizu imunomodulatornog efekta EPS-CG11 korišćena su dva in vivo modela inflamacije izazvane karageninom: model inflamatornog bola i model peritonitisa kod pacova Wistar soja. U eksperimentu inflamatornog bola praćeni su: vremenski tok razvoja hiperalgezije i edema šapica nakon profilaktiĉke sistemske primene EPS-CG11, ekspresija medijatora inflamacije (IL-1β, TNF-α, IL-6 i iNOS), infiltracija neutrofila (ekspresija MPO enzima) i aktivacija/infiltracija monocita (ekspresija CD14 markera)...Isolation and characterization of bacterial biomolecules involved in the interaction with the receptors of the host cells represent the key factor for understanding the mechanisms of probiotic action of lactobacilli. Novel studies regarding probiotic bacteria have been focused on the identification of biomolecules which can modulate different signaling pathways in human cells. All molecules that originate from probiotics which are responsible for its positive effects on the host’s health are called postbiotics. Their application represents the safe alternative to the use of live bacteria and its immunostimulating potential. This research aimed to test the possibility of using postbiotics in alleviation of pain symptoms and analgesics side effects. More precisely, two main objectives of this research were: (i) to examine the influence of bioactive molecules of selected strains of lactobacilli on the autophagy process in the hepatocytes, in vitro, as well as protective effect of these molecules in paracetamol-induced toxicity and (ii) to examine the potential immunomodulatory effect of exopolysaccharide (EPS-CG11) isolated from Lactobacillus paraplantarum BGCG11 strain, in in vivo experimental models of inflammation. Experiments in the hepatocytes culture included monitoring the degree of damage of HepG2 cells exposed to the toxic paracetamol concentration and the autophagy process, with the aim of identification of potential mechanism of postbiotic action. Methodologically, the cell viability was monitored by MTT and LDH assays. Autophagy was monitored by Western blot analysis, in order to determine the expression of the p62/SQSTM1 protein and the accumulation of the liposoluble form of the LC3 protein. Further, the autophagy was analyzed by monitoring the expression of BECN1, Atg5, p62/SQSTM1 and PINK1 genes and the autophagy flux. For the analysis of the immunomodulatory effect of EPS-CG11, two in vivo models of carrageenan-induced inflammation were used: an inflammatory pain model and a peritonitis model in the Wistar rats..

Fulminant Wegener's granulomatosis: A case report

Introduction. Granulomatosis Wegener is anti-neutrophil cytoplasmic antibodies (ANCAs)-associated systemic vasculitis of unknown etiology. It is manifested as granulomatous necrotizing inflammation of the upper and lower parts of the respiratory tract, glomerulonephritis and systemic vasculitis involving most frequently the skin and oral mucous membrane. Sera markers of this disease are c-ANCA and p-ANCA. Case report. We presented a female patient aged 52 years with purpuric spots that had appeared on the lower legs ten months before admission to our hospital. The disease ran an aggressive course, and a month before admission hemorrhagic bullae, skin ulcers, hoarseness, dyspnea, generalized arthralgia, fatigue and fever had rapidly developed. Histopathological examination of a skin sample revealed necrotizing vasculitis, so that sera markers concentrations were elevated (c-ANCA, p-ANCA). There was a perforation of the nasal septum found on rhinoscopy. During hospitalization acute abdominal pain occurred, a possible tumor in the small intestine and possible granulomas in the liver were seen by multislice computed tomography (MSCT) examination, with normal findings on the lungs and kidneys. The treatment started with methylprednisolone: 500 mg/d i.v. infusion for consecutive 3 days, then 60 mg/d. On exploratory laparotomy small bowel perforation and diffuse peritonitis were found. Unstable in the postoperative period, the patient died on the day 12 of hospitalization. Conclusion. The reported patient was with fulminant Wegener’s granulomatosis, dominantly with skin changes and with gastrointestinal manifestation. This case accents the need for rapid systemic clinical evaluation in a severely ill patient with unclear diagnosis

RclS Sensor Kinase Modulates Virulence of Pseudomonas capeferrum

Signal transduction systems are the key players of bacterial adaptation and survival. The orthodox two-component signal transduction systems perceive diverse environmental stimuli and their regulatory response leads to cellular changes. Although rarely described, the unorthodox three-component systems are also implemented in the regulation of major bacterial behavior such as the virulence of clinically relevant pathogen P. aeruginosa. Previously, we described a novel three-component system in P. capeferrum WCS358 (RclSAR) where the sensor kinase RclS stimulates the intI1 transcription in stationary growth phase. In this study, using rclS knock-out mutant, we identified RclSAR regulon in P. capeferrum WCS358. The RNA sequencing revealed that activity of RclSAR signal transduction system is growth phase dependent with more pronounced regulatory potential in early stages of growth. Transcriptional analysis emphasized the role of RclSAR in global regulation and indicated the involvement of this system in regulation of diverse cellular activities such as RNA binding and metabolic and biocontrol processes. Importantly, phenotypic comparison of WCS358 wild type and Delta rclS mutant showed that RclS sensor kinase contributes to modulation of antibiotic resistance, production of AHLs and siderophore as well as host cell adherence and cytotoxicity. Finally, we proposed the improved model of interplay between RclSAR, RpoS and LasIR regulatory systems in P. capeferrum WCS358

Effects of soybean carbohydrates and lactobacillus helveticus bgra43 on metabolic processes in rat colon

Aim of this work was to assess the metabolic and physiological changes that occurred in the hind gut of rats after feeding with soybean carbohydrates alone and in combination with Lactobacillus helveticus BGRA43. Wistar rats were gavaged with soybean flour for 28 days. The parameters assessed included fecal volatile organic compounds, and L-lactate, reducing sugars, proteins, ammonia and water levels in the colonic lumen. The presence of lactic acid (LAB), sulfate reducing (SRB) and methanogenic bacteria was assessed by semi-quantitative PCR. Malondialdehyde levels as well as lymphoid tissue size in ileal and colonic mucosa were also evaluated. On the basics of the results obtained, correlation network was created, setting the parameters tested in research in two metabolic groups: saccharolytic and proteolytic fermentation group. The principal finding of the study is a negative correlation between oral administration of BGRA43 and increase of parameters related to carbohydrate fermentation in the gut, and a positive correlation to factors related to proteolytic fermentation. On the contrary, soybean carbohydrates were correlated with increased values of factors related to carbohydrate catabolism. Different effects of BGRA43 and soybean carbohydrates on metabolic processes in colonic lumen indicate the possibility of applying the BGRA43 in alleviating the gastrointestinal symptoms occurring after consuming hardly digestible carbohydrates

Probiotička karakterizacija soja Limosilactobacillus fermentum BGHV110 i njegov uticaj na urođeni imunski odgovor kod Caenorhabditis elegans

Probiotic lactobacilli exhibit the potential to promote health benefits for the host. Thanks to its numerous beneficial effects on human health, Limosilactobacillus fermentum stood out as an excellent candidate for the development of commercial probiotic preparations aiming to prevent community-acquired infections. In this study, several in vitro tests, including biofilm formation assay, assessment of antibiotic susceptibility, survival in simulated gastrointestinal tract conditions and attachment to intestinal Caco-2 cells, were used to estimate the safety and probiotic potential of L. fermentum BGHV110 strain. Additionally, Caenorhabditis elegans was used as an in vivo model system for the evaluation of L. fermentum BGHV110 influence on the host’s innate immune response. The results revealed that L. fermentum BGHV110 strain showed an excellent capability to survive harsh conditions of the gut, to attach to intestinal Caco-2 cells and to stimulate conserved p38 MAPK immunity pathway and expression of the clc-1 claudin-like gene and antimicrobial peptides in C. elegans in order to enhance the immune response against pathogens. Finally, L. fermentum BGHV110 showed no virulence traits and susceptibility to tested antibiotics, confirming its safety status which enables it to be applied as a future probiotic

Lactobacillus fermentum Postbiotic-induced Autophagy as Potential Approach for Treatment of Acetaminophen Hepatotoxicity

The aim of this study was to investigate the potential of postbiotics originated from Lactobacillus fermentum BGHV110 strain (HV110) to counteract acetaminophen (APAP)-induced hepatotoxicity in HepG2 cells. This strain was selected according to its autophagy inducing potential, based on previous studies reporting protective role of autophagy in APAP caused cellular damage. Cell viability was assessed using MTT and LDH assays, while autophagy was monitored by qPCR analysis of BECN1, Atg5, p62/SQSTM1, and PINK1 mRNA expression and by Western blot analysis of p62/SQSTM1 and lipidated LC3 accumulation. Our results showed that detrimental effect of APAP on cell viability was suppressed in the presence of HV110 which was linked with increased conversion of LC3 protein and p62/SQSTM1 protein degradation. Additionally, higher p62/SQSTM1 and PINK1 mRNA transcription were noticed in cells co-treated with APAP/HV110, simultaneously. In conclusion, this study suggests that HV110 enhances activation of PINK1-dependent autophagy in HepG2 cells and its eventual co-supplementation with APAP could be potentially used for alleviation of hepatotoxic side effects caused by APAP overdose

Probiotic characterization of Limosilactobacillus fermentum BGHV110 strain and its influence on innate immune response in Caenorhabditis elegans

Probiotic lactobacilli exhibit the potential to promote health benefits for the host. Thanks to its numerous beneficial effects on human health, Limosilactobacillus fermentum stood out as an excellent candidate for the development of commercial probiotic preparations aiming to prevent community-acquired infections. In this study, several in vitro tests, including biofilm formation assay, assessment of antibiotic susceptibility, survival in simulated gastrointestinal tract conditions and attachment to intestinal Caco-2 cells, were used to estimate the safety and probiotic potential of L. fermentum BGHV110 strain. Additionally, Caenorhabditis elegans was used as an in vivo model system for the evaluation of L. fermentum BGHV110 influence on the host's innate immune response. The results revealed that L. fermentum BGHV110 strain showed an excellent capability to survive harsh conditions of the gut, to attach to intestinal Caco-2 cells and to stimulate conserved p38 MAPK immunity pathway and expression of the clc-1 claudin-like gene and antimicrobial peptides in C. elegans in order to enhance the immune response against pathogens. Finally, L. fermentum BGHV110 showed no virulence traits and susceptibility to tested antibiotics, confirming its safety status which enables it to be applied as a future probiotic

Coronaphobia – What Do Coronaphobia Scales Measure? An Analysis of 12 Open Instruments and their Correlates

Previous studies confirmed the psychological, psychosomatic, and economic consequences of the COVID-19 outbreak, which lead to the introduction of a new concept of coronaphobia as a persistent and excessive fear of the novel coronavirus. With the beginning of the pandemic, the interest in coronaphobia-related measurement began and until 2021, 12 instruments were created, with a total of 28 (sub)scales. The first aim of this study was to explore the joined factor structure of these measurements. The second aim was to explore a wide range of correlates of coronaphobia (sociodemographic characteristics, general anxiety disorder, Big Five traits, knowledge about coronavirus, and political orientation). The sample included 347 participants (42.1% male) from the general population of Serbia and data were collected in April 2021. Results showed that only one component could be extracted based on 28 (sub)scales of coronaphobia, meaning that physiological, cognitive, emotional, and behavioral aspects of coronaphobia are rather intercorrelated. Furthermore, among explored correlates, general anxiety disorder had the highest contribution to the explanation of coronaphobia. Additionally, Openness showed a negative, and age showed a positive contribution to the explanation of coronaphobia. Our results suggest that coronaphobia should be understood as a syndrome that captures physiological, cognitive, behavioral, and emotional aspects, and that individuals who are already prone to anxiety disorders are more prone to coronaphobia as well

A novel thermostable YtnP lactonase from Stenotrophomonas maltophilia inhibits Pseudomonas aeruginosa virulence in vitro and in vivo

Infections caused by multidrug-resistant pathogens are one of the biggest challenges facing the healthcare system today. Quorum quenching (QQ) enzymes have the potential to be used as innovative enzyme-based antivirulence therapeutics to combat infections caused by multidrug-resistant pathogens. The main objective of this research was to describe the novel YtnP lactonase derived from the clinical isolate Stenotrophomonas maltophilia and to investigate its antivirulence potential against multidrug-resistant Pseudomonas aeruginosa MMA83. YtnP lactonase, the QQ enzyme, belongs to the family of metallo-β-lactamases. The recombinant enzyme has several advantageous biotechnological properties, such as high thermostability, activity in a wide pH range, and no cytotoxic effect. High-performance liquid chromatography analysis revealed the activity of recombinant YtnP lactonase toward a wide range of N-acyl-homoserine lactones (AHLs), quorum sensing signaling molecules, with a higher preference for long-chain AHLs. Recombinant YtnP lactonase was shown to inhibit P. aeruginosa MMA83 biofilm formation, induce biofilm decomposition, and reduce extracellular virulence factors production. Moreover, the lifespan of MMA83-infected Caenorhabditis elegans was prolonged with YtnP lactonase treatment. YtnP lactonase showed synergistic inhibitory activity in combination with gentamicin and acted additively with meropenem against MMA83. The described properties make YtnP lactonase a promising therapeutic candidate for the development of next-generation antivirulence agents