Circulating low-molecular-weight (poly)phenol metabolites in the brain: unveiling in vitro and in vivo blood-brain barrier transport.

Circulating metabolites resulting from colonic metabolism of dietary (poly)phenols are highly abundant in the bloodstream, though still marginally explored, particularly concerning their brain accessibility. Our goal is to disclose (poly)phenol metabolites' blood-brain barrier (BBB) transport, in vivo and in vitro, as well as their role at BBB level. For three selected metabolites, benzene-1,2-diol-3-sulfate/benzene-1,3-diol-2-sulfate (pyrogallol-sulfate - Pyr-sulf), benzene-1,3-diol-6-sulfate (phloroglucinol-sulfate - Phlo-sulf), and phenol-3-sulfate (resorcinol-sulfate - Res-sulf), BBB transport was assessed in human brain microvascular endothelial cells (HBMEC). Their potential in modulating in vitro BBB properties at circulating concentrations was also studied. Metabolites' fate towards the brain, liver, kidney, urine, and blood was disclosed in Wistar rats upon injection. Transport kinetics in HBMEC highlighted different BBB permeability rates, where Pyr-sulf emerged as the most in vitro BBB permeable metabolite. Pyr-sulf was also the most potent regarding BBB properties improvement, namely increased beta(ß)-catenin membrane expression and reduction of zonula occludens-1 membrane gaps. Whereas no differences were observed for transferrin, increased expression of caveolin-1 upon Pyr-sulf and Res-sulf treatments was found. Pyr-sulf was also capable of modulating gene and protein expression of some solute carrier transporters. Notably, each of the injected metabolites exhibited a unique tissue distribution in vivo, with the remarkable ability to almost immediately reach the brain.

Semiquantitative Paper-Based Microfluidic Surrogate Virus Neutralization Test for SARS-CoV-2 Neutralizing Antibodies.

Neutralizing antibodies (nAbs) produced from infection or vaccination play an important role in acquired immunity. Determining virus-specific nAb titers is a useful tool for measuring aquired immunity in an individual. The standard methods to do so rely on titrating serum samples against live virus and monitoring viral infection in cultured cells which requires high biosafety level containment. The surrogate virus neutralization test (sVNT) reduces the biohazards and it is suitable for designing rapid test device in a lateral flow assay (LFA) format. Here, we introduce the fabrication and development of a unique paper-based LFA device for determining the level of SARS-CoV-2 nAb in a sample with a semiquantitative direct colorimetric readout. A LFA-based gradient assay design was used to facilitate the sVNT, where the spike glycoprotein receptor binding domain (RBD) and angiotensin-converting enzyme 2 (ACE2) stand in as proxies for viruses and cells, respectively. The gradient assay employed multiple test dots of ACE2 spotted in increasing concentration along the sample flow path and gold nanoparticle-conjugated RBD for readout. In this way, the number of developed spots is inversely proportional to the concentration of nAbs present in the sample. The assay was tested with both standard solutions of nAb as well as human serum samples. We have demonstrated that the device can effectively provide semiquantitative test results of nAbs by direct instrument-free colorimetric detection.

An unusual variant of type I common bile duct duplication associated with ampullary carcinoma.

Common bile duct duplications represent exceptionally rare congenital anomalies of the biliary tract. In this case report we document an unusual variant of common bile duct duplication in a 79-year-old man who underwent a pancreaticoduodenectomy for ampullary cancer. The duplication consisted of two unseparated, completely-layered, common bile ducts which originated above the cystic duct junction and terminated prior to the point of insertion into the pancreas, where the two lumens converged into a single duct. Duplication of the bile duct is rare and often goes undetected. In the present case, the anomaly was found incidentally in a patient who had a pancreaticoduodenectomy for an ampullary carcinoma. However, duplication may be associated with choledocholithiasis, cholangitis, pancreatitis, and pancreaticobiliary malignancies and it is important to be aware of the condition.

The Risk of Virus Emergence in South America: A Subtle Balance Between Increasingly Favorable Conditions and a Protective Environment.

South American ecosystems host astonishing biodiversity, with potentially great richness in viruses. However, these ecosystems have not yet been the source of any widespread, epidemic viruses. Here we explore a set of putative causes that may explain this apparent paradox. We discuss that human presence in South America is recent, beginning around 14,000 years ago; that few domestications of native species have occurred; and that successive immigration events associated with Old World virus introductions reduced the likelihood of spillovers and adaptation of local viruses into humans. Also, the diversity and ecological characteristics of vertebrate hosts might serve as protective factors. Moreover, although forest areas remained well preserved until recently, current brutal, sudden, and large-scale clear cuts through the forest have resulted in nearly no ecotones, which are essential for creating an adaptive gradient of microbes, hosts, and vectors. This may be temporarily preventing virus emergence. Nevertheless, the mid-term effect of such drastic changes in habitats and landscapes, coupled with explosive urbanization and climate changes, must not be overlooked by health authorities.

Salivary immunoglobulin levels and periodontal indices in Brazilian children with and without type 1 diabetes.

This cross-sectional study evaluated the association between salivary immunoglobulins, plaque index, and gingival index in Brazilian children with and without type 1 diabetes mellitus (DM1). The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist for the reporting of observational studies was followed. The DM1 group had 38 children, and an equal number of volunteers matched by sex and age were recruited as controls. Clinical examination was performed for plaque index and gingival index determination. Non-stimulated whole saliva was collected. Concentrations of IgA, IgG, and IgM were determined by ELISA test. Data were tested by the Kolmogorov-Smirnov, Mann-Whitney, and Spearman tests and a multiple linear regression model (p<0.05) was performed. Gingival index was higher in the Control (DM1: 0.16±0.17; Control: 0.24±0.23, p=0.040). In DM1, there was a correlation between IgA and age (rho=0.371, p=0.024), IgM and IgG (rho=0.459, p=0.007), and IgM and gingival index (rho=0.394, p=0.014). In DM1, multiple linear regression showed that age (p=0.041; ß=0.363), gingival index (p=0.041; ß=0.398), and plaque index (p=0.008; ß=-0.506) were good predictors of IgA levels in saliva. Thus, IgA was the only researched immunoglobulin that was directly associated with plaque and gingival indices in Brazilian children with DM1, but not in control subjects.

Original article: novelty of Canadian manufacture nasopharyngeal swabs for collection of samples being tested for SARS-CoV-2 in a pandemic setting.

Objectives: The COVID-19 pandemic caused a global shortage of nasopharyngeal (NP) swabs, required for RT-PCR testing. Canadian manufacturers were contacted to share NP swab innovations. The primary objective was to determine whether novel NP test swabs were comparable to commercially available swabs regarding user characteristics, ability to collect a specimen, and diagnostic performance using RT-PCR testing. Methods: Participants were randomized by swab (test/control) and nostril (left/right). A calculated positive percent agreement ≥90% was considered successful. Mean Ct values of viral genes and housekeeping gene (RNase P) were considered similar if a Ct difference ≤ 2 between control and test group was obtained. There also was a qualitative assessment of swabs usability. Results: 647 participants were enrolled from Huaycan Hospital in Lima, Peru, distributed over 8 NP swabs brands. Seven brands agreed to share their results. There were no statistically significant differences between the test swabs of these 7 brands and control swabs. Conclusion: All the seven brands are comparable to the commercially available flocked swabs used for SARS-CoV-2 regarding test results agreement, ability to collect a specimen, and user characteristics.

Barriers to participation in biosampling-based translational research: A cross-sectional survey of Canadian critical care researchers.

BACKGROUND AND OBJECTIVE: Collection of biosamples for translational research studies is vital for understanding biological pathways, discovering disease-related biomarkers, and identifying novel therapeutic targets. However, a lack of infrastructure for sample procurement, processing, storage, and shipping may hinder the ability of clinical research units to effectively engage in translational research. The purpose of this study was to identify the barriers to biosampling-based translational research in the critical care setting in Canada. METHODS: We administered an online survey to members of the Canadian Critical Care Trials Group (CCCTG), the Canadian Critical Care Translational Biology Group (CCCTBG), and the Canadian Critical Care Research Coordinators Group (CCCRCG). The survey focused on participants' personal experience of biosampling research, research infrastructure, motivating factors, and perceived barriers. RESULTS: We received 59 responses from 31 sites, including 6 community intensive care unit (ICU) sites. The overall response rate was 11.3%. The majority of respondents were research coordinators (44%), followed by clinician-investigators (33.8%), graduate students (10.2%), and PhD-investigators (8.5%). Although most (63.8%) respondents reported an interest in participating in translational research, they also reported that their ICUs were currently contributing to a third of the number of translational studies compared to clinical studies. For respondents with experience in participating in translational research studies, the most common barriers were lack of funding, lack of time, and insufficient research staff. For respondents without previous experience, the perceived facilitators were more interest from their research group, improved training/mentorship, increased funding, and better access to laboratory equipment. CONCLUSIONS: Our survey found that the majority of participants were interested in and recognize the value of participating in biosampling-based translational research but lacked funding, time, and research personnel trained in biosampling protocols. Our survey also identified factors that might encourage participation at new sites. Addressing these barriers will be a key step towards increasing translational research capacity across Canada.

Single-Domain Antibody-Gold Nanoparticle Bioconjugates as Immunosensors for the Detection of Hantaviruses.

INTRODUCTION: Hantavirus, a zoonotic pathogen, causes severe syndromes like hemorrhagic fever with renal syndrome (HFRS), sometimes fatal in humans. Considering the importance of detecting the hantavirus antigen, the construction of an immunosensor is essential. The structural and functional characteristics of camelid nanobodies (VHHs) encourage their application in the areas of nanobiotechnology, therapeutics, diagnostics, and basic research. Therefore, this study aimed to standardize stable bioconjugates using gold nanoparticles (AuNPs) and VHHs, in order to develop immunobiosensors for the diagnosis of hantavirus infection. METHODS: Immobilized metal affinity chromatography (IMAC) was performed to obtain purified recombinant anti-hantavirus nucleocapsid nanobodies (anti-prNΔ85 VHH), while AuNPs were synthesized for bioconjugation. UV-visible spectrophotometry and transmission electron microscopy (TEM) analysis were employed to characterize AuNPs. RESULTS: The bioconjugation stability parameters (VHH-AuNPs), analyzed by spectrophotometry, showed that the ideal pH value and VHH concentration were obtained at 7.4 and 50 µg/mL, respectively, after addition of 1 M NaCl, which induces AuNP aggregation. TEM performed before and after bioconjugation showed uniform, homogeneous, well-dispersed, and spherical AuNPs with an average diameter of ~ 14 ± 0.57 nm. Furthermore, high-resolution images revealed a thin white halo on the surface of the AuNPs, indicating the coating of the AuNPs with protein. A biosensor simulation test (dot blot-like [DB-like]) was performed in stationary phase to verify the binding and detection limits of the recombinant nucleocapsid protein from the Araucária hantavirus strain (prN∆85). DISCUSSION: Using AuNPs/VHH bioconjugates, a specific interaction was detected between 5 and 10 min of reaction in a dose-dependent manner. It was observed that this test was sensitive enough to detect prNΔ85 at concentrations up to 25 ng/µL. Considering that nanostructured biological systems such as antibodies conjugated with AuNPs are useful tools for the development of chemical and biological sensors, the stability of the bioconjugate indicates proficiency in detecting antigens. The experimental results obtained will be used in a future immunospot assay or lateral flow immunochromatography analysis for hantavirus detection.

Application of Fourier-Transform Infrared Spectroscopy for the Assessment of Wine Spoilage Indicators: A Feasibility Study.

Wine aroma is one of the most frequently used and explored quality indicators. Typically, its assessment involves estimating the volatile composition of wine or highly trained assessors conducting sensory analysis. However, current methodologies rely on slow, expensive and complicated analytical procedures. Additionally, sensory evaluation is inherently subjective in nature. Therefore, the aim of this work is to verify the feasibility of using FTIR spectroscopy as a fast and easy methodology for the early detection of some of the most common off-odors in wines. FTIR spectroscopy was combined with partial least squares (PLS) regression for the simultaneous measurement of isoamyl alcohol, isobutanol, 1-hexanol, butyric acid, isobutyric acid, decanoic acid, ethyl acetate, furfural and acetoin. The precision and accuracy of developed calibration models (R2P > 0.90, range error ratio > 12.1 and RPD > 3.1) proved the ability of the proposed methodology to quantify the aforementioned compounds.

Development of monoclonal antibodies against oropouche virus and its applicability to immunohistochemical diagnosis.

Orthobunyavirus oropouche ense virus (OROV), the causative agent of Oropouche fever, is widely dispersed in Brazil and South America, causing sporadic outbreaks. Due to the similarity of initial clinical symptoms caused by OROV with other arboviruses found in overlapping geographical areas, differential diagnosis is challenging. As for most neglected tropical diseases, there is a shortage of reagents for diagnosing and studying OROV pathogenesis. We therefore developed and characterized mouse monoclonal antibodies and, one of them recognizes the OROV nucleocapsid in indirect immunofluorescent (IFA) and immunohistochemistry (IHC) assays. Considering that it is the first monoclonal antibody produced for detecting OROV infections, we believe that it will be useful not only for diagnostic purposes but also for performing serological surveys and epidemiological surveillance on the dispersion and prevalence of OROV in Brazil and South America.

Financial constraints and incentives for the prevention and control of obesity in the state of Rio de Janeiro, Brazil. / Constrangimentos e incentivos financeiros para a prevenção e o controle da obesidade no estado do Rio de Janeiro, Brasil.

The present study aimed to analyze how these changes, both at the national and state levels, could affect the conditions of the implementation of obesity prevention and control (OCP) actions in primary health care (PHC) in the Rio de Janeiro State from 2014 to 2021. This study was based on policy analysis methods that emphasize the understanding of the implementation contexts, as well as the induction mechanisms and government incentives for the development of actions and integration of two projects that analyzed the OPC actions in PHC in the 92 municipalities of RJS between 2014 and 2018 (PPSUS-RJS) and between 2019 and 2021 (PEO-RJS). The results indicate that, by 2016, it was possible to observe the positive impacts of the structuring of PHC and the federal induction mechanisms in RJS. However, inflections in the expansion and funding of PHC contributed to the weakening of units, teams, and strategies, and led to retraction of resources for both state and municipal actions. Between 2016-2018, RJS's political and financial scenario deteriorated due to national crises, and the positive counterpoints since then were the induction mechanisms and federal resources that remained, in addition to the technical areas of the RJS-HD and state co-financing resources.

O estudo analisou como as inflexões político-econômicas de financiamento e de estruturação do Sistema Único de Saúde podem ter afetado as condições de implementação de ações de prevenção e controle da obesidade (PCO) na atenção primária à saúde (APS) no estado do Rio de Janeiro (ERJ) entre 2014 e 2021. Fundamentou-se em referenciais de análise de políticas, considerando contexto de implementação, antecedentes históricos, mecanismos de indução e incentivos governamentais para o desenvolvimento das ações de PCO. Baseou-se em dois projetos realizados nos 92 municípios do ERJ entre 2014 e 2018 (PPSUS-ERJ) e 2019-2021 (PEO-ERJ), pautados em análise documental, entrevistas e grupos focais com profissionais e gestores da APS. Até 2016, percebe-se os impactos positivos da estruturação da APS e dos mecanismos de indução federais. No entanto, as inflexões na expansão e no financiamento da APS contribuíram para o enfraquecimento de unidades, equipes e estratégias, além de uma retração de recursos para as ações estaduais e municipais. Entre 2016-2018, a crise política e financeira do ERJ foi potencializada pelas crises nacionais, e os contrapontos positivos desde então foram os mecanismos de indução e recursos federais que permaneceram, além das áreas técnicas da SES-ERJ e do cofinanciamento estadual.

Tiny Guides, Big Impact: Focus on the Opportunities and Challenges of miR-Based Treatments for ARDS.

Acute Respiratory Distress Syndrome (ARDS) is characterized by lung inflammation and increased membrane permeability, which represents the leading cause of mortality in ICUs. Mechanical ventilation strategies are at the forefront of supportive approaches for ARDS. Recently, an increasing understanding of RNA biology, function, and regulation, as well as the success of RNA vaccines, has spurred enthusiasm for the emergence of novel RNA-based therapeutics. The most common types of RNA seen in development are silencing (si)RNAs, antisense oligonucleotide therapy (ASO), and messenger (m)RNAs that collectively account for 80% of the RNA therapeutics pipeline. These three RNA platforms are the most mature, with approved products and demonstrated commercial success. Most recently, miRNAs have emerged as pivotal regulators of gene expression. Their dysregulation in various clinical conditions offers insights into ARDS pathogenesis and offers the innovative possibility of using microRNAs as targeted therapy. This review synthesizes the current state of the literature to contextualize the therapeutic potential of miRNA modulation. It considers the potential for miR-based therapeutics as a nuanced approach that incorporates the complexity of ARDS pathophysiology and the multifaceted nature of miRNA interactions.

Fermentation of coffee fruit with sequential inoculation of Lactiplantibacillus plantarum and Saccharomyces cerevisiae: effect on sensory attributes and chemical composition of the beans.

This study has innovative aspects related to the use of sequential inoculation technique in the coffee bean fermentation process: the inoculation of Lactiplantibacillus plantarum followed by Saccharomyces cerevisiae, in the fermentation of coffee fruit for the production of specialty natural coffees. The objective was to evaluate the effect of this technique and of the total fermentation time on the sensory attributes of the coffee beverage and on the organic acid profile, bioactive compounds, and fatty acid profile of the beans. The fermentation of coffee fruit with sequential inoculation resulted in greater acidity of the beverage and contributed to increases of up to 2 points in coffee fermented. The total fermentation time was directly related to the organic acid content, and the longer the total fermentation time was, the greater the organic acid content. The fatty acid content and bioactive compound content showed little variation among treatments.

Self-medication cases reported to a poison information center in Brazil from 2014 to 2020.

INTRODUCTION: Self-medication is the use of drugs to treat self-diagnosed illnesses or symptoms, on one's own initiative, without the guidance of a healthcare professional. Poison centers play an important role in understanding the relationship between self-medication and poisoning. The objective of this study is to evaluate the clinical and epidemiological profile of patients exposed to and/or poisoned by different drugs through self-medication. METHODS: This retrospective, cross-sectional, and descriptive study analyzed data from 2014 to 2020, provided by the Toxicological Information and Assistance Center of Santa Catarina, Brazil. Data were selected, tabulated, and analyzed by using descriptive statistics and group comparison with the chi-square test or Fisher's exact test. A P value <0.05 was considered statistically significant. RESULTS: There were 683 cases of self-medication identified. Most patients were female (62.8 percent) and between 20 and 29 years old (26.1 percent). A toxic dose of a substance was administered in only 22.8 percent of the cases, and five deaths were recorded. The most commonly used medications were anxiolytics (18 percent), followed by analgesics and antipyretics (15.4 percent). Paracetamol was the drug used in three of the five cases that resulted in deaths. DISCUSSION: This study demonstrates the prevalence of self-medication among women aged between 20 and 29 years old. Statistical analysis failed to show a relationship between a toxic dose and clinical manifestations. Anxiolytics, analgesics, and antipyretics are the most reported medications probably because healthcare professionals are mostly the ones who contact the center. Analgesics and antipyretics account for more than fifty percent of the deaths caused by self-medication in the present report. Some limitations such as secondary sources are related. CONCLUSION: We highlight the importance of health professionals in promoting the rational use of medicines, as well as poison centers in assisting the population and raising their awareness regarding the issue.

Obstructive Sleep Apnea Syndrome in Heavy Truck Drivers: A Portuguese Prospective Cohort Study.

INTRODUCTION: Heavy truck drivers with untreated obstructive sleep apnea (OSA) are at higher risk of driving accidents. This study aims to estimate the prevalence of OSA and to identify the most frequent symptoms and comorbidities in heavy truck drivers. METHODS: This cohort study included the employees of a Portuguese transport company between 2019 and 2022. A home sleep apnea test (HSAT) was performed on all patients. SPSS® was used for statistical analysis, and a p-value lower than 0.05 was considered statistically significant. RESULTS: A total of 86 truck drivers were included, with a mean age of 48.02 years (min. 24, max 66) and a mean body mass index (BMI) of 30.14±4.4 kg/m². After performing an HSAT, it was found that 77.9% of drivers (n=67) had OSA, with a mean apnea-hypopnea index (AHI) of 16.72±14.69 events/hour. Concerning diagnosed patients, 44.78% (n=30) had mild, 31.32% (n=23) moderate, and 20.89% (n=14) severe OSA. Obesity, hypertension, and dyslipidemia had a statistically significant association. There were no statistically significant differences between patients with and without type II diabetes mellitus. The presence of nighttime and daytime symptoms had a statistically significant correlation with OSA diagnosis. Despite only eight patients reporting a high score on the Epworth Sleepiness Scale (ESS), 14 patients reported previous episodes of falling asleep while driving, which might be associated with the non-valorization of daytime sleepiness in these patients. The patients who reported previous episodes of falling asleep while driving were older and had higher BMI, higher ESS, and higher AHI. CONCLUSIONS: In the evaluated truck drivers, the prevalence of OSA was very high (77.9%), which reinforces the importance of screening for this pathology since, when left untreated, it is a major risk factor for exercising their profession safely.

Cardiac tissue model of immune-induced dysfunction reveals the role of free mitochondrial DNA and the therapeutic effects of exosomes.

Despite tremendous progress in the development of mature heart-on-a-chip models, human cell-based models of myocardial inflammation are lacking. Here, we bioengineered a vascularized heart-on-a-chip with circulating immune cells to model severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced acute myocarditis. We observed hallmarks of coronavirus disease (COVID-19)-induced myocardial inflammation, as the presence of immune cells augmented the secretion of proinflammatory cytokines, triggered progressive impairment of contractile function, and altered intracellular calcium transients. An elevation of circulating cell-free mitochondrial DNA (ccf-mtDNA) was measured first in the heart-on-a-chip and then validated in COVID-19 patients with low left ventricular ejection fraction, demonstrating that mitochondrial damage is an important pathophysiological hallmark of inflammation-induced cardiac dysfunction. Leveraging this platform in the context of SARS-CoV-2-induced myocardial inflammation, we established that administration of endothelial cell-derived exosomes effectively rescued the contractile deficit, normalized calcium handling, elevated the contraction force, and reduced the ccf-mtDNA and cytokine release via Toll-like receptor-nuclear factor κB signaling axis.

Fermentation of coffee fruit with sequential inoculation of Lactiplantibacillus plantarum and Saccharomyces cerevisiae: Effects on volatile composition and sensory characteristics.

Mixed starter cultures of lactic acid bacteria and yeasts used in the production of fermented foods, including coffee, can improve the sensory quality and food safety. The objective of this study was to evaluate the effects of fermentation of coffee with inoculation of Lactiplantibacillus plantarum followed by Saccharomyces cerevisiae and the effects of fermentation time on the aroma and flavor of the coffee beverage and on the volatile composition of the roasted coffee beans. The coffee was fermented for 48 h or 96 h after inoculation of Lactiplantibacillus plantarum followed by inoculation of Saccharomyces cerevisiae or the respective controls. The aroma and flavor of the coffee beverage fermented with sequential inoculation showed complexity, with a predominance of fruity and fermented sensory notes. Forty-seven volatile compounds were identified. In addition, the sequentially inoculated coffees had greater formation of volatiles and led to greater perception of fruity and fermented flavor and aroma.

Efficacy and Safety of Umbilical Cord-Derived Mesenchymal Stromal Cell Therapy in Preclinical Models of Sepsis: A Systematic Review and Meta-analysis.

BACKGROUND: In preclinical studies, mesenchymal stromal cells (MSCs), including umbilical cord-derived MSCs (UC-MSCs), demonstrate the ability to modulate numerous pathophysiological processes related to sepsis; however, a systematic synthesis of the literature is needed to assess the efficacy of UC-MSCs for treating sepsis. OBJECTIVE: To examine the effects of UC-MSCs on overall mortality (primary outcome) as well as on organ dysfunction, coagulopathy, endothelial permeability, pathogen clearance, and systemic inflammation (secondary outcomes) at prespecified time intervals in preclinical models of sepsis. METHODS: A systematic search was conducted on Embase, Ovid MEDLINE, and Web of Science up to June 20, 2023. Preclinical controlled studies using in vivo sepsis models with systemic UC-MSC administration were included. Meta-analyses were conducted and expressed as odds ratios (OR) and ratios of the weighted means with 95% CI for categorical and continuous data, respectively. Risk of bias was assessed with the SYRCLE tool. RESULTS: Twenty-six studies (34 experiments, n = 1258 animals) were included in this review. Overall mortality was significantly reduced with UC-MSC treatment as compared to controls (OR: 0.26, 95% CI: 0.18-0.36). At various prespecified time intervals, UC-MSCs reduced surrogate measures of organ dysfunction related to the kidney, liver, and lung; reduced coagulopathy and endothelial permeability; and enhanced pathogen clearance from multiple sites. UC-MSCs also modulated systemic inflammatory mediators. No studies were rated as low risk across all SYCLE domains. CONCLUSIONS: These results demonstrate the efficacy of UC-MSC treatment in preclinical sepsis models and highlight their potential as a therapeutic intervention for septic shock.

Proteomics of serum-derived extracellular vesicles are associated with the severity and different clinical profiles of patients with COVID-19: An exploratory secondary analysis.

BACKGROUND AIMS: Coronavirus disease 2019 (COVID-19) is characterized by a broad spectrum of clinical manifestations with the potential to progress to multiple organ dysfunction in severe cases. Extracellular vesicles (EVs) carry a range of biological cargoes, which may be used as biomarkers of disease state. METHODS: An exploratory secondary analysis of the SARITA-2 and SARITA-1 datasets (randomized clinical trials on patients with mild and moderate/severe COVID-19) was performed. Serum-derived EVs were used for proteomic analysis to identify enriched biological processes and key proteins, thus providing insights into differences in disease severity. Serum-derived EVs were separated from patients with COVID-19 by size exclusion chromatography and nanoparticle tracking analysis was used to determine particle concentration and diameter. Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) was performed to identify and quantify protein signatures. Bioinformatics and multivariate statistical analysis were applied to distinguish candidate proteins associated with disease severity (mild versus moderate/severe COVID-19). RESULTS: No differences were observed in terms of the concentration and diameter of enriched EVs between mild (n = 14) and moderate/severe (n = 30) COVID-19. A total of 414 proteins were found to be present in EVs, of which 360 were shared while 48 were uniquely present in severe/moderate compared to mild COVID-19. The main biological signatures in moderate/severe COVID-19 were associated with platelet degranulation, exocytosis, complement activation, immune effector activation, and humoral immune response. Von Willebrand factor, serum amyloid A-2 protein, histone H4 and H2A type 2-C, and fibrinogen ß-chain were the most differentially expressed proteins between severity groups. CONCLUSION: Exploratory proteomic analysis of serum-derived EVs from patients with COVID-19 detected key proteins related to immune response and activation of coagulation and complement pathways, which are associated with disease severity. Our data suggest that EV proteins may be relevant biomarkers of disease state and prognosis.

Using a targeted metabolomics approach to explore differences in ARDS associated with COVID-19 compared to ARDS caused by H1N1 influenza and bacterial pneumonia.

RATIONALE: Acute respiratory distress syndrome (ARDS) is a life-threatening critical care syndrome commonly associated with infections such as COVID-19, influenza, and bacterial pneumonia. Ongoing research aims to improve our understanding of ARDS, including its molecular mechanisms, individualized treatment options, and potential interventions to reduce inflammation and promote lung repair. OBJECTIVE: To map and compare metabolic phenotypes of different infectious causes of ARDS to better understand the metabolic pathways involved in the underlying pathogenesis. METHODS: We analyzed metabolic phenotypes of 3 ARDS cohorts caused by COVID-19, H1N1 influenza, and bacterial pneumonia compared to non-ARDS COVID-19-infected patients and ICU-ventilated controls. Targeted metabolomics was performed on plasma samples from a total of 150 patients using quantitative LC-MS/MS and DI-MS/MS analytical platforms. RESULTS: Distinct metabolic phenotypes were detected between different infectious causes of ARDS. There were metabolomics differences between ARDSs associated with COVID-19 and H1N1, which include metabolic pathways involving taurine and hypotaurine, pyruvate, TCA cycle metabolites, lysine, and glycerophospholipids. ARDSs associated with bacterial pneumonia and COVID-19 differed in the metabolism of D-glutamine and D-glutamate, arginine, proline, histidine, and pyruvate. The metabolic profile of COVID-19 ARDS (C19/A) patients admitted to the ICU differed from COVID-19 pneumonia (C19/P) patients who were not admitted to the ICU in metabolisms of phenylalanine, tryptophan, lysine, and tyrosine. Metabolomics analysis revealed significant differences between C19/A, H1N1/A, and PNA/A vs ICU-ventilated controls, reflecting potentially different disease mechanisms. CONCLUSION: Different metabolic phenotypes characterize ARDS associated with different viral and bacterial infections.