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Effects of urban airborne particulate matter exposure on the human upper respiratory tract microbiome: a systematic review

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RESPIRATORY RESEARCH 2025年第1期26卷 1-18页

作者： Arca-Lafuente, Sonia Nunez-Corcuera, Beatriz Ramis, Rebeca Karakitsios, Spyros Sarigiannis, Denis Dos Santos, Saul Garcia Fernandez-Rodriguez, Amanda briz, veronica Inst Hlth Carlos III Natl Ctr Microbiol Viral Hepatitis Reference & Res Lab Madrid Spain Inst Salud Carlos III ISCIII Ctr Invest Biomed Red Enfermedades Infecciosas CIB Madrid Spain Inst Hlth Carlos III ISCIII Natl Ctr Environm Hlth Air Pollut Area Madrid Spain Inst Hlth Carlos III ISCIII Natl Ctr Epidemiol Chron Dis Dept Canc & Environm Epidemiol Unit Madrid Spain Inst Salud Carlos III Ctr Invest Biomed Red Epidemiol & Salud Publ CIBER Madrid Spain Aristotle Univ Thessaloniki Dept Chem Engn Lab Environm Engn Enve Lab Thessaloniki Greece Natl Hellen Res Fdn Athens Greece

Exposure to air pollutants has a direct impact on human health, resulting in increased mortality rates. Airborne particulate matter (PM) has major adverse effects on health and can be classified as high-risk respiratory particles (fine/PM2.5, aerodynamic diameter < 2.5 m) or thoracic particles (coarse/PM10, aerodynamic diameter < 10 m). In addition, airborne PM can carry microbial communities that alter the commensal microbiota and lead to dysbiosis. Our aim was to synthesize the current research evidence describing the association between air pollution exposure and the microbiome composition of the upper respiratory tract (URT) of the adult population. In this work, a systematic search of the PubMed, EMBASE and Scopus databases was conducted. A total of 9 studies published from 2018 to 2023 were included. 66.5% of the participants were exposed to PM2.5 concentrations higher than 40 mu g/m(3), and data showed that PM2.5 atmospheric levels were positively correlated with PM10 (r(s) = 0.95, p < 0.001). All the reviewed studies performed 16S rRNA sequencing of the V3-V4 region from URT samples, using different methods. Overall, evidence of URT microbiome alterations after high PM exposure was observed, with seasonal and geographical influence. Discordant findings were found about bacterial diversity, with a predominant decrease after exposure to high PM levels. Regarding microbiome composition, the relative abundance of the Actinobacteria phylum declined following exposure to high levels of PM, but that of Bacteroidetes and Fusobacteria increased. The studies showed a low-middle risk of bias due to heterogeneity regarding sample processing, sequencing methods, and confounder control. To confirm the observed evidence of an association between PM levels and alterations in the URT microbiome, we strongly recommend that future research work be conducted in accordance with standard guidelines for reporting microbiome studies. In summary, the entry of fine and coarse

关键词： PM2.5 PM10 Microbiome Dysbiosis Upper respiratory tract

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Extracellular vesicles derived microRNAs as non-invasive markers of liver fibrosis in chronically infected HCV patients: a pilot study

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NON-CODING RNA RESEARCH 2025年 12卷 132-140页

作者： Cairoli, Victoria Valle-Millares, Daniel Ryan, Pablo Dominguez, Lourdes Martin-Carbonero, Luz de los Santos, Ignacio De Matteo, Elena Ameigeiras, Beatriz De Sousa, Marcela briz, veronica Preciado, Maria, V Fernandez-Rodriguez, Amanda Valva, Pamela Ricardo Gutierrez Childrens Hosp Multidisciplinary Inst Invest Pediat Pathol IMIPP Pathol Div Lab Mol BiolCONICETGCB C1425EFD Buenos Aires Argentina Hlth Inst Carlos III ISCIII Natl Ctr Microbiol CNM Unit Viral Infect & Immun Madrid 28222 Spain Infanta Leonor Univ Hosp Dept Internal Med HIV Unit Madrid Spain Inst Salud Carlos III Ctr Invest Biomed Red Enfermedades Infecciosas CIB Madrid 28222 Spain Hosp 12 Octubre imas12 Biomed Res Inst Imas12 Internal Med Dept Res Inst Madrid Spain La Paz Univ Hosp Internal Med Dept Infect Dis Unit Madrid Spain La Princesa Univ Hosp Hosp Princesa Dept Internal Med & Infect Dis Madrid 28006 Spain Hosp Ramos Mejia Liver Unit C1221ADC Buenos Aires Argentina Inst Salud Carlos III Viral Hepatitis Reference & Res Lab Ctr Nacl Microbiol Madrid 28222 Spain

Extracellular vesicles (EVs) are an increasingly promising tool for liquid biopsy in liver diseases. Hepatitis C Virus (HCV) infection, alone or together with Human Immunodeficiency Virus (HIV) infection significantly impacts on the microRNA (miRNA) EVs content resembling chronic hepatitis C (CHC) progression. The objective of the study was to delve into the intricate EVs-miRNA profiles in CHC patients with different liver fibrosis stages, aiming to pinpoint non-invasive markers capable of distinguishing significant fibrosis. Plasma EV-miRNAs from 50 CHC patients (HCV+ and HCV+/HIV+) stratified in no significant (F < 2) and significant (F >= 2) fibrosis, were massively sequenced. General linear models (GLM) were used to identify significantly differential expressed (SDE) miRNAs according to liver fibrosis stages (F >= 2 and F < 2). Dysregulated biological pathways were subsequently analyzed in silico for the following groups: i) all patients;ii) HCV+;and iii) HCV+/HIV+. Multiple-ordered logistic regression analysis was performed to develop a score to identify F >= 2 cases. The diagnostic potential of both the SDE miRNAs and the developed score was assessed using ROC curve analysis. With respect to all CHC patients, two SDE miRNAs (hsa-miR-122-5p and hsa-miR-92a-3p) were identified which regulate genes related to cytoskeleton organization. Regarding their diagnostic performance to discriminate F >= 2, both miRNAs individually demonstrated acceptable diagnostic values. However, their combined use in a new score enhanced their diagnostic performance (AUROC = 0.833). In the HCV+ subgroup, 8 SDE miRNAs (hsa-miR-122-5p, hsa-miR-320c, hsa-miR-3615, hsa-miR-320a-3p, hsa-miR-374b-5p, hsa-let-7a-3p, hsa-miR-199a-5p, hsa-miR-142-5p), which regulate macrophage activity and cell growth/death regulation, were recognized. Among them, hsa-miR-3615 displayed the highest diagnostic performance to discriminate F >= 2 (AUROC = 0.936). With respect to HCV+/HIV+, 18 SDE miRNAs (hsa-miR-4

关键词： Hepatitis C infections MicroRNAs Extracellular vesicles Fibrosis Biomarkers

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Epidemiological trend of hepatitis C-related liver events in Spain (2000-2015): A nationwide population-based study

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EUROPEAN JOURNAL OF INTERNAL MEDICINE 2020年 75卷 84-92页

作者： Mate-Cano, Irene Alvaro-Meca, Alejandro Ryan, Pablo Resino, Salvador briz, veronica Primary Hlth Ctr Ensanche de Vallecas Madrid Spain Inst Hlth Carlos III Natl Ctr Microbiol Lab Reference & Res Viral Hepatitis Madrid Spain Rey Juan Carlos Univ Dept Prevent Med & Publ Hlth Madrid Spain Hosp Univ Infanta Leonor Serv Med Interna Madrid Spain Inst Invest Sanitaria Gregorio Maranon IiSGM Madrid Spain

Objective: Analysis the epidemiological trends of hospital admissions, intra-hospital deaths, and costs related to chronic hepatitis C (CHC) taking into account four major clinical stages [compensated cirrhosis (CC), end-stage liver disease (ESLD), hepatocellular carcinoma (HCC), and liver transplantation (LT)] in Spain. Methods: Retrospective study in patients with chronic hepatitis C and a hospital admission in the Spanish Minimum Basic Data Set from 2000 to 2015. Outcome variables were admission, death, length of hospital stay and costs. Results: A total of 868,523 hospital admissions with CHC (25.5% CC, 25.3% ESLD, 8.6% HCC, and 2.5% LT) were identified. Overall rates of admission and mortality increased from 2000-2003 to 2004-2007, but after 2008, these rates stabilized and/or decreased. An upward trend was found for hospitalization percentage in CC (from 22.3% to 30%;p< 0.001), ESLD (from 23.9% to 27.1%;p< 0.001), HCC (from 7.4% to 11%;p< 0.001), and LT (from 0.07% to 0.10%;p= 0.003). An upward trend was also found for case fatality rate, except in ESLD (p = 0.944). Gender and age influenced the evolution of hospitalization rates and mortality differently. The length of hospital stay showed a significant downward trend in all strata analyzed (p < 0.001). Cost per patient had a significant upward trend (p < 0.001), except in LT, and a decrease from 2008-2011 to 2012-2015 in CC (p = 0.025), HCC (p < 0.001), and LT (p = 0.050) was found. Conclusion: The initial upward trend of the disease burden in CHC has changed from 2000 to 2015 in Spain, improving in many parameters after 2004-2007, particularly in the 2012-2015 calendar period.

关键词： Chronic hepatitis C Cirrhosis, hepatocarcinoma, liver transplantation End stage liver disease Hospital admissions Mortality ICD9CM codes

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Nanotechnology: A reality for diagnosis of HCV infectious disease

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JOURNAL OF INFECTION 2020年第1期80卷 8-15页

作者： Arca-Lafuente, Sonia Martinez-Roman, Paula Mate-Cano, Irene Madrid, Ricardo briz, veronica Inst Hlth Carlos III Natl Ctr Microbiol Lab Reference & Res Viral Hepatitis Madrid Spain BioAssays SL C Faraday7Parque Cient Madrid Madrid 28049 Spain

Hepatitis C virus (HCV) is the primary etiologic agent of liver cirrhosis or hepatocellular carcinoma. HCV elevated infection rates are mostly due to the lack of an accurate and accessible screening and diagnosis, especially in low- and middle-income countries. Conventional HCV diagnostic algorithm consists of a serological test followed by a nucleic acid test. This sequence of tests is time consuming and not affordable for low-resource settings. Nanotechnology have introduced new promising tests for the diagnose of infectious diseases. Based on the employment of nanoparticles and other nanomaterials which lead to highly sensitive and specific nanoscale tests, most of them target pathogen genome. Implementation of nanoscale tests, which are affordable, portable and easy to use by non-specialized personal, would improve HCV diagnosis algorithm. In this review, we have summed up the current emerging nanotechnology tools, which will improve actual screening and treatment programs, and help to reach HCV elimination proposal. (C) 2019 The Author(s). Published by Elsevier Ltd on behalf of The British Infection Association.

关键词： Diagnosis Hepatitis C virus Nanotecnology

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Prevalence of relevant NS5A resistance-associated substitutions to elbasvir in genotype la hepatitis C virus patients in Spain

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ENFERMEDADES INFECCIOSAS Y MICROBIOLOGIA CLINICA 2018年第5期36卷 262-267页

作者： Palladino, Claudia Esteban-Cartelle, Beatriz Mate-Cano, Irene Sanchez-Carrillo, Marta Resino, Salvador briz, veronica Univ Lisbon Fac Farm Inst Invest Medicamento iMed ULisboa Lisbon Portugal Inst Salud Carlos III Ctr Nacl Microbiol Lab Referencia & Invest Hepatitis Virales Unidad Infecc Viral & Inmunidad Madrid Spain Hosp Henares Dept Enfermedades Infecciosas Madrid Spain

Resistance-associated substitutions (RASs) to the new HCV NS5A inhibitor elbasvir may limit its efficacy and lead to virological failure in HCV-GT1a-infected patients. There are no data outside clinical trials evaluating their prevalence and impact in grazoprevir/elbasvir in GT1a-infected patients in Spain. A multicentre cross-sectional study of 632 initial patients was conducted. In 13 of these patients, the sample could not be amplified or a consensus sequence by Sanger sequencing could not be performed. Ultimately, 617 HCV-G1a-infected individuals treated at 84 Spanish hospitals from the 17 autonomous communities plus the 2 autonomous cities of Spain were analysed. HCV population sequencing was used to identify RAS to elbasvir and the mutational pattern and drug sensitivity were confirmed by geno2pheno[HCV]. Viruses bearing RASs to elbasvir were present in 6.2% of HCV-G1a infected patients. The most common RASs were the Y93C/H/N and Q30E/H/R (2.4% and 2.3%, respectively). Only 3.4% of the identified RASs to elbasvir conferred reduced susceptibility to elbasvir by geno2pheno[HCV], which exclusively identified the positions Q30H/R (n = 7) and Y93C/H/N (n = 8) as single mutations and Q3OH + Y93H (n = 4) and Q3OR + Y93H (n = 2) as double mutations as the major RASs to elbasvir. A lower prevalence of RASs to elbasvir was observed in our HCV-G1a Spanish cohort than reported previously in clinical trials evaluating patients from the USA. This information may be essential to guide the implementation of grazoprevir/elbasvir in Spain and to manage G1a-infected patients. (C) 2017 Elsevier Espana, S.L.U. and Sociedad Espafiola de Enfermedades Infecciosas y Microbiologia Clinica. All rights reserved.

关键词： Direct-acting antiviral agents Genotype substitution Hepatitis C virus / human immunodeficiency virus-coinfection Elbasvir implementation Prevalence

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Impact of antiretroviral therapy on viral tropism in HIV-infected patients followed longitudinally for over 5 years

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JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY 2008年第2期61卷 405-410页

作者： briz, veronica Poveda, Eva Gonzalez, Maria del Mar Martin-Carbonero, Luz Gonzalez-Gonzalez, Rocio Soriano, Vincent Hosp Carlos III Dept Infect Dis Madrid Spain

Background: Viral tropism plays a major role in HIV pathogenesis and may influence the activity of entry inhibitors. The impact of antiretroviral therapy use on the dynamics of viral tropism over time is still poorly understood. Patients and methods: HIV co-receptor usage was determined longitudinally for over 5 years in 237 plasma specimens collected from 73 distinct HIV-1-infected drug-naive individuals, 42 of whom initiated antiretroviral therapy thereafter and 31 who remained untreated. Viral tropism was estimated genotypically using the phenotype predictor software webPSSM, considering as X4 virus populations those with pure X4 and dual/mixed X4/R5 variants. Results: At baseline, the prevalence of X4 viruses was 3.2% and 14.6% in patients who remained untreated and in those who initiated antiretroviral therapy, respectively (P = 0.112). Mean plasma HIV-RNA was lower in the former compared with the latter (3.8 +/- 0.9 versus 4.5 +/- 0.9 log;P < 0.004), while conversely the mean CD4 count was greater in untreated than in those who had begun therapy (536 +/- 191 versus 278 +/- 192 cells/mm(3);P<0.001). During follow-up, switch in co-receptor use occurred overall in 26% of the study population, with no significant differences between the groups. Emergence of X4 viruses was significantly associated with lower CD4 counts regardless of antiretroviral treatment exposure. Conclusions: The use of antiretroviral therapy does not seem to influence the selection of X4 viruses, which mainly occur in patients with low CD4 counts.

关键词： HAART entry inhibitors pathogenesis

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Prevalence of darunavir resistance mutations in HIV-1-infected patients failing other protease inhibitors

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JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY 2007年第4期60卷 885-888页

作者： Poveda, Eva De Mendoza, Carmen Martin-Carbonero, Luz Corral, Angelica briz, veronica Gonzalez-Lahoz, Juan Soriano, Vincent Hosp Carlos III Dept Infect Dis Madrid Spain

Background: To estimate to what extent darunavir might be effective in patients failing distinct protease inhibitors (PIs), the genotypic resistance scores recently reported for the drug were examined in a large clinical HIV-1 drug resistance database. Methods: All clinical specimens from HIV-infected patients failing PI-based regimens referred for drug resistance testing between 1999 and 2007 to a reference centre in Madrid were analysed. Darunavir-specific resistance mutations listed by the September 2006 IAS-USA panel update were considered. Results: A total of 1021 genotypes from patients failing lopinavir (39.2%), nelfinavir (28.1%), saquinavir (14.5%), indinavir (13.7%), atazanavir (6.6%), fosamprenavir (5.3%) and tipranavir (1.1%) were identified. The prevalence of major darunavir resistance mutations was I50V 2.1%, I54M 1.3%, L76V 2.7% and I84V 14.5%. For minor darunavir resistance mutations, the rates were V11I 3.3%, V32I 3.9%, L33F 11%, I47V 2.1%, I54L 2.3%, G73S 12.8% and L89V 2.4%. Overall, 6.7% (n = 68) of the genotypes had three or more darunavir resistance mutations, which corresponded to a mean total number of PI resistance mutations of 12.3 +/- 1.9. In the multivariate analysis, prior fosamprenavir failure, prior saquinavir failure, the total number of PI resistance mutations and the number of prior PIs used were all independently associated with having more darunavir resistance mutations. Conclusions: The prevalence of darunavir resistance mutations is low in patients failing other PI-based regimens, although prior failure to amprenavir and saquinavir might produce more cross-resistance to darunavir. Thus, darunavir may be a good option for patients who have failed other PI-based regimens.

关键词： new antiretrovirals genetic barrier salvage therapies

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Prevalence of X4 tropic HIV-1 variants in patients with differences in disease stage and exposure to antiretroviral therapy

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JOURNAL OF MEDICAL VIROLOGY 2007年第8期79卷 1040-1046页

作者： Poveda, Eva briz, veronica de Mendoza, Carmen Benito, Jose Miguel Corral, Angelica Zahonero, Natalia Lozano, Sara Gonzalez-Lahoz, Juan Soriano, Vincent Hosp Carlos 3 Dept Infect Dis Madrid 28029 Spain

Viral tropism plays an important role in HIV pathogenesis. However, its correlation with the clinical outcome and following exposure to antiretroviral drugs are still unclear. HIV-1 co-receptor usage was examined in 206 infected individuals: 67 seroconverters, 52 chronically drug-naive, and 87 antiretroviral-experienced patients. The V3 loop was sequenced from plasma HIV-RNA and co-receptor usage was inferred using a phenotype predictor software (http://genomiac2. ***:8080/wetcat/***), which classifies V3 sequences as R5 or X4. The overall prevalence of X4 viruses was 26.2%, with significant differences among groups: 13.4% in seroconverters, 25% in drug-naive, and 36.8% in antiretroviral-experienced patients (P=0.001). The presence of X4 variants in the latter group was associated with higher viral load (P=0.002) but not with lower CD4 counts. There was no association between HIV tropism and gender, transmission route or age. Neither with the CCR5 Delta 32 genotype. Moreover, no association was found between HIV-1 tropism and drug resistance mutations nor with failure to regimens based on either protease inhibitors or non-nucleoside reverse transcriptase inhibitors. Finally, no significant association was found between IL-7 plasma levels with HIV-1 tropism. In summary, X4 viruses are particularly frequent among anti retroviral-experienced patients with high viral loads, irrespective of the CD4 count. Thus, CCR5 antagonists should be used with special caution in this subset of patients.

关键词： HIV tropism co-receptor antagonists pathogenesis

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Development of water-soluble polyanionic carbosilane dendrimers as novel and highly potent topical anti-HIV-2 microbicides

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NANOSCALE 2015年第35期7卷 14669-14683页

作者： briz, veronica Sepulveda-Crespo, Daniel Diniz, Ana Rita Borrego, Pedro Rodes, Berta Javier de la Mata, Francisco Gomez, Rafael Taveira, Nuno Angeles Munoz-Fernandez, Ma Univ Gregorio Maranon Gen Hosp Lab InmunoBiol Mol Madrid Spain Inst Invest Sanitaria Gregorio Maranon Spanish HIV HGM Biobank Madrid Spain Networking Res Ctr Bioeng Biomat & Nanomed CIBER Madrid Spain Univ Lisbon Fac Pharm Res Inst Med iMed P-1699 Lisbon Portugal Hosp La Paz Fdn Invest Biomed Madrid Spain Univ Alcala de Henares Dept Quim Inorgon Madrid Spain Inst Super Ciencias Saude Egas Moniz Monte De Caparica Portugal

The development of topical microbicide formulations for vaginal delivery to prevent HIV-2 sexual transmission is urgently needed. Second-and third-generation polyanionic carbosilane dendrimers with a silicon atom core and 16 sulfonate (G2-S16), napthylsulfonate (G2-NS16) and sulphate (G3-Sh16) end-groups have shown potent and broad-spectrum anti-HIV-1 activity. However, their antiviral activity against HIV-2 and mode of action have not been probed. Cytotoxicity, anti-HIV-2, anti-sperm and antimicrobial activities of dendrimers were determined. Analysis of combined effects of triple combinations with tenofovir and raltegravir was performed by using CalcuSyn software. We also assessed the mode of antiviral action on the inhibition of HIV-2 infection through a panel of different in vitro antiviral assays: attachment, internalization in PBMCs, inactivation and cell-based fusion. Vaginal irritation and histological analysis in female BALB/c mice were evaluated. Our results suggest that G2-S16, G2-NS16 and G3-Sh16 exert anti-HIV-2 activity at an early stage of viral replication inactivating the virus, inhibiting cell-to-cell HIV-2 transmission, and blocking the binding of gp120 to CD4, and the HIV-2 entry. Triple combinations with tenofovir and raltegravir increased the anti-HIV-2 activity, consistent with synergistic interactions (CIwt: 0.33-0.66). No vaginal irritation was detected in BALB/c mice after two consecutive applications for 2 days with 3% G2-S16. Our results have clearly shown that G2-S16, G2-NS16 and G3-Sh16 have high potency against HIV-2 infection. The modes of action confirm their multifactorial and non-specific ability, suggesting that these dendrimers deserve further studies as potential candidate microbicides to prevent vaginal/rectal HIV-1/HIV-2 transmission in humans.

关键词： Sulfur compounds

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Molecular modeling studies demonstrate key mutations that could affect the ligand recognition by influenza AH1N1 neuraminidase

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JOURNAL OF MOLECULAR MODELING 2015年第11期21卷 1-14页

作者： Ramirez-Salinas, Gema L. Garcia-Machorro, J. Quiliano, Miguel Zimic, Mirko briz, veronica Rojas-Hernandez, Saul Correa-Basurto, J. Escuela Super Med Inst Politecn Nacl Secc Estudios Posgrad & Invest Lab Modelado Mol & Bioinformat Mexico City 11340 DF Mexico Escuela Super Med Inst Politecn Nacl Lab Med Conservac Mexico City 11340 DF Mexico Univ Peruana Cayetano Heredia Lab Invest & Desarrollo Unidad Bioinformat & Biol Mol Lima Peru Inst Salud Carlos III Ctr Nacl Microbiol Unidad Infecc Viral Inmunidad Madrid Spain Natl Polytech Inst Immunol Lab Sch Med Mexico City DF Mexico

The goal of this study was to identify neuraminidase (NA) residue mutants from human influenza AH1N1 using sequences from 1918 to 2012. Multiple alignment studies of complete NA sequences (5732) were performed. Subsequently, the crystallographic structure of the 1918 influenza (PDB ID: 3BEQ-A) was used as a wild-type structure and three-dimensional (3-D) template for homology modeling of the mutated selected NA sequences. The 3-D mutated NAs were refined using molecular dynamics (MD) simulations (50 ns). The refined 3-D models were used to perform docking studies using oseltamivir. Multiple sequence alignment studies showed seven representative mutations (A232V, K262R, V263I, T264V, S367L, S369N, and S369K). MD simulations applied to 3-D NAs showed that each NA had different active-site shapes according to structural surface visualization and docking results. Moreover, Cartesian principal component analyses (cPCA) show structural differences among these NA structures caused by mutations. These theoretical results suggest that the selected mutations that are located outside of the active site of NA could affect oseltamivir recognition and could be associated with resistance to oseltamivir.

关键词： Docking Influenza A H1N1 Molecular dynamics simulations Mutations Neuraminidase

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