RESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Chaihu Guizhi Decoction (CGD) has a long history of use in China for the treatment of influenza, which involves the use of a variety of aromatic herbs. Our previous studies have found that the contents of aromatic constituents in CGD affected the efficacy of treatment of influenza-infected mice, suggesting a clue that essential oil from CGD may play a relatively important role in ameliorating influenza induced pneumonia. AIM OF THE STUDY: To evaluate the anti-influenza potential of essential oil derived from Chaihu Guizhi Decoction (CGD-EO), to characterize and predict the key active components in CGD-EO, and to explore the mechanism of action of CGD-EO. MATERIALS AND METHODS: CGD-EO was obtained by steam distillation, and the components of the essential oil were characterized by gas chromatography-mass spectrometry (GC-MS) in conjunction with the retention index. The constituents absorbed into the blood of mice treated with CGD-EO were analyzed by headspace solid phase microextraction gas chromatography/mass spectrometry (HS-SPME-GC/MS). The potential anti-influenza active constituents and their possible action pathway were predicted by simulation using a network pharmacology approach. The protective effect of CGD-EO and its major components on H1N1/PR8-infected cells was determined using the CCK8 assay kit. Mice infected with influenza A virus H1N1/PR8 were administered different doses of CGD-EO orally and the body weights and lung weights were recorded. Mice with varying degrees of H1N1/PR8 infection were administered CGD-EO orally, and their daily weight, water consumption, and clinical indicators were recorded. Necropsies were conducted on days 3 and 5, during which lung weights were measured and lung tissues were preserved. Furthermore, the mRNA expression of the H1N1/PR8 virus and inflammatory factors in lung tissue was analyzed using RT-qPCR. RESULTS: (E)-cinnamaldehyde was the most abundant compound in the CGD-EO. The results of serum medicinal chemistry combined with network pharmacological analysis indicated that (E)-cinnamaldehyde and 3-phenyl-2-propenal may be potential active components of the CGD-EO anti-influenza, and may be involved in the NF-κB signalling pathway. In vitro studies have demonstrated that both CGD-EO and cinnamaldehyde exert a protective effect on MDCK cells infected with H1N1/PR8. In a 0.5 TCID50 H1N1/PR8-induced influenza model, mice treated with CGD-EO at a dose of 63.50 µg/kg exhibited a reduction in lung index, pathological lung lesions, and H1N1/PR8 viral gene levels. In addition, CGD-EO treatment was found to regulate the levels of inflammatory cytokines, including IL-6, TNF-α, and IFN-γ. Moreover, following three days of administration, an upregulation of NF-κB mRNA levels in mouse lung tissue was observed in response to CGD-EO treatment. CONCLUSIONS: The findings of our study indicate CGD-EO exerts a protective effect against H1N1-induced cytopathic lesions in vitro and is capable of alleviating H1N1-induced pneumonitis in mice. Moreover, it appears to be more efficacious in the treatment of mild symptoms of H1N1 infection. Studies have demonstrated that CGD-EO has antiviral potential to attenuate influenza-induced lung injury by modulating inflammatory cytokines and NF-κB signalling pathways during the early stages of influenza infection. It is possible that (E)-cinnamaldehyde is a potential active ingredient in the anti-influenza efficacy of CGD-EO.
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Antivirales , Medicamentos Herbarios Chinos , Aceites Volátiles , Infecciones por Orthomyxoviridae , Animales , Aceites Volátiles/farmacología , Medicamentos Herbarios Chinos/farmacología , Ratones , Infecciones por Orthomyxoviridae/tratamiento farmacológico , Antivirales/farmacología , Ratones Endogámicos BALB C , Neumonía Viral/tratamiento farmacológico , Masculino , Células de Riñón Canino Madin Darby , Perros , Subtipo H1N1 del Virus de la Influenza A/efectos de los fármacos , Pulmón/efectos de los fármacos , Pulmón/patología , Pulmón/virología , Pulmón/metabolismo , Humanos , Femenino , Neumonía/tratamiento farmacológico , Neumonía/virología , Neumonía/metabolismoRESUMEN
Surprisingly, the 1977 "Russian flu" H1N1 pandemic influenza virus was genetically indistinguishable from strains that had circulated decades earlier but had gone extinct in 1957. This essay puts forward the most plausible chronology to explain the reemergence of the 1977 H1N1 pandemic virus: (1) in January-February 1976, a self-limited small outbreak of a swine H1N1 influenza virus occurred among Army personnel at Fort Dix, New Jersey; (2) in March 1976, the US launched a nationwide H1N1 swine influenza vaccine program; (3) other countries then also launched their own H1N1 R&D efforts; (4) a new H1N1 outbreak, genetically unrelated to the Fort Dix swine virus but indistinguishable from previously extinct H1N1 viruses, was detected early in 1977 in China; (5) the leading Chinese influenza virologist later disclosed that the Chinese military had conducted large H1N1 vaccine R&D studies in 1976. It is likely that the resurrected H1N1 influenza viruses were laboratory-stored strains that were unfrozen and studied as part of the emergency response to a perceived epidemic threat, and that accidentally escaped. The fear of a possible H1N1 pandemic was the critical factor that gave rise to the actual H1N1 pandemic, resulting in an avoidable "self-fulfilling prophecy pandemic."
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Subtipo H1N1 del Virus de la Influenza A , Vacunas contra la Influenza , Gripe Humana , Pandemias , Humanos , Gripe Humana/epidemiología , Gripe Humana/historia , Gripe Humana/virología , Historia del Siglo XX , Estados Unidos/epidemiología , China/epidemiología , Personal Militar , New Jersey/epidemiología , AnimalesRESUMEN
In March 2023, our pediatric intensive care unit (PICU) retrospectively examined six cases of pediatric necrotizing tracheobronchitis (NTB), focusing on co-infections with influenza A virus (IAV) and Staphylococcus aureus (S. aureus). This study aimed to elucidate NTB's clinical characteristics, diagnostics, and therapeutic approaches. Diagnostics included symptom assessment, microbiological testing that confirmed all patients were positive for IAV H1N1 with a predominant S. aureus co-infection, and bronchoscopy. The patients predominantly exhibited fever, cough, and dyspnea. Laboratory analysis revealed decreased lymphocyte counts and elevated infection markers like C-reactive protein and procalcitonin. Chest computed tomography (CT) scans detected tracheobronchial obstructions in half of the cases, while bronchoscopy showed severe mucosal congestion, edema, necrosis, and purulent-hemorrhagic exudates. Treatments encompassed comprehensive strategies like oxygen therapy, intubation, bronchoscopic interventions, thoracentesis, oseltamivir, and a regimen of antibiotics. Our findings suggested potential correlations between clinical markers, notably lymphocyte count and procalcitonin, and clinical interventions such as the number of rescues and intensive care unit (ICU) duration. This research highlights the importance of early detection and the role of bronchoscopy and specific markers in assessing NTB, advocating for continued research in larger cohorts to better understand its clinical trajectory and refine treatment approaches for this challenging pediatric disease.
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Bronquitis , Coinfección , Gripe Humana , Infecciones Estafilocócicas , Staphylococcus aureus , Traqueítis , Humanos , Coinfección/diagnóstico , Masculino , Femenino , Infecciones Estafilocócicas/diagnóstico , Infecciones Estafilocócicas/complicaciones , Gripe Humana/complicaciones , Gripe Humana/diagnóstico , Preescolar , Traqueítis/diagnóstico , Traqueítis/microbiología , Traqueítis/complicaciones , Bronquitis/diagnóstico , Bronquitis/microbiología , Bronquitis/complicaciones , Estudios Retrospectivos , Staphylococcus aureus/aislamiento & purificación , Lactante , Niño , Broncoscopía/métodos , Unidades de Cuidado Intensivo Pediátrico , Subtipo H1N1 del Virus de la Influenza A/aislamiento & purificación , Necrosis , Virus de la Influenza A/aislamiento & purificaciónAsunto(s)
Influenza Pandémica, 1918-1919 , Gripe Humana , Neumonía Viral , Humanos , Masculino , Adulto Joven , Dolor en el Pecho/diagnóstico , Dolor en el Pecho/etiología , Diagnóstico Diferencial , Disnea/diagnóstico , Disnea/etiología , Pulmón/diagnóstico por imagen , Pulmón/patología , Radiografía Torácica , Fiebre/diagnóstico , Fiebre/etiología , Tos/diagnóstico , Tos/etiología , Gripe Humana/complicaciones , Gripe Humana/diagnóstico , Gripe Humana/epidemiología , Gripe Humana/prevención & control , Influenza Pandémica, 1918-1919/historia , Subtipo H1N1 del Virus de la Influenza A/aislamiento & purificación , Historia del Siglo XX , Historia del Siglo XXI , Monitoreo Epidemiológico , Neumonía Viral/complicaciones , Neumonía Viral/diagnóstico , Preparación para una Pandemia , Vacunas contra la Influenza/administración & dosificaciónRESUMEN
BACKGROUND The purpose of the study was to determine the level of antihemagglutinin antibodies in the serum of patients in the geriatric population in Doctor's Surgery NZOZ Nucleus Warsaw, Poland, during the epidemic season 2021/2022 using the hemagglutination inhibition assay (HAI), according to anti-influenza and anti-COVID-19 vaccination, age, and sex. MATERIAL AND METHODS Serum samples taken from 256 patients aged 65 to 99 years were examined for anti-hemagglutinin antibodies and protective levels of antibodies against antigens: A/Victoria/2570/2019 (H1N1)pdm09, A/Cambodia/e0826360/2020(H3N2), B/Washington/02/2019 (B/Victoria lineage), and B/Phuket/3073/2013 (B/Yamagata lineage) of the quadrivalent influenza vaccine for epidemic season 2021/2022. RESULTS The highest protective level, ie, the percentage of people with antibody titers ≥40 was 87.5% and was recorded for subtype A/Cambodia/e0826360/2020(H3N2), the dominant type causing infections in the epidemic season 2021/2022 confirmed by molecular biology methods. Geometric mean titer (GMT) values and protective levels for B/Washington/02/2019 (B/Victoria lineage) antigen were higher for men than women (respectively 38.4 vs 67.6; P<0.001 and 58.0% vs 74.6%; P<0.001). The protective levels of antibodies among patients vaccinated vs unvaccinated against COVID-19 were higher for B/Washington/02/2019 (B/Victoria lineage) and B/Phuket/3073/2013 (B/Yamagata lineage) antigens (64.2% vs 44.4%; P=0.023 and 78.6% vs 55.6%; P=0.004). GMT values for vaccinated against COVID-19 were also higher. There were no significant differences between younger (65-79 years) and older (≥80 years) seniors. CONCLUSIONS The analysis shows differences in the level of individual antibodies, GMT and the protective level depending on subtypes of influenza A or B virus, B/Victoria or B/Yamagata lineage, sex, and previous vaccination history against influenza and COVID-19.
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Anticuerpos Antivirales , COVID-19 , Vacunas contra la Influenza , Gripe Humana , SARS-CoV-2 , Humanos , Anciano , Polonia/epidemiología , Masculino , Femenino , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Gripe Humana/prevención & control , Gripe Humana/inmunología , Gripe Humana/epidemiología , Vacunas contra la Influenza/inmunología , Anciano de 80 o más Años , COVID-19/prevención & control , COVID-19/inmunología , COVID-19/epidemiología , SARS-CoV-2/inmunología , Vacunas contra la COVID-19/inmunología , Factores Sexuales , Vacunación , Subtipo H3N2 del Virus de la Influenza A/inmunología , Glicoproteínas Hemaglutininas del Virus de la Influenza/inmunología , Factores de Edad , Subtipo H1N1 del Virus de la Influenza A/inmunología , Pruebas de Inhibición de Hemaglutinación/métodos , Estaciones del AñoRESUMEN
The vast majority of data obtained from sequence analysis of influenza A viruses (IAVs) have revealed that nonstructural 1 (NS1) proteins from H1N1 swine, H3N8 equine, H3N2 avian and the correspondent subtypes from dogs have a conserved four C-terminal amino acid motif when independent cross-species transmission occurs between these species. To test the influence of the C-terminal amino acid motifs of NS1 protein on the replication and virulence of IAVs, we systematically generated 7 recombinants, which carried naturally truncated NS1 proteins, and their last four C-terminal residues were replaced with PEQK and SEQK (for H1N1), EPEV and KPEI (for H3N8) and ESEV and ESEI (for H3N2) IAVs. Another recombinant was generated by removing the C-terminal residues by reverse genetics. Remarkably, the ESEI and KPEI motifs circulating in canines largely contributed efficient replication in cultured cells and these had enhanced virulence. In contrast, the avian ESEV motif was only responsible for high pathogenicity in mice. We examined the effects of these motifs upon interferon (IFN) induction. The 7 mutant viruses replicated in vitro in an IFN-independent manner, and the canine SEQK motif was able to induced higher levels of IFN-ß in human cell lines. These findings shed further new light on the role of the four C-terminal residues in replication and virulence of IAVs and suggest that these motifs can modulate viral replication in a species-specific manner.
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Secuencias de Aminoácidos , Subtipo H1N1 del Virus de la Influenza A , Infecciones por Orthomyxoviridae , Proteínas no Estructurales Virales , Replicación Viral , Proteínas no Estructurales Virales/genética , Proteínas no Estructurales Virales/metabolismo , Proteínas no Estructurales Virales/química , Animales , Perros , Virulencia , Ratones , Subtipo H1N1 del Virus de la Influenza A/genética , Subtipo H1N1 del Virus de la Influenza A/patogenicidad , Subtipo H1N1 del Virus de la Influenza A/fisiología , Infecciones por Orthomyxoviridae/virología , Humanos , Células de Riñón Canino Madin Darby , Ratones Endogámicos BALB C , Enfermedades de los Perros/virología , Subtipo H3N2 del Virus de la Influenza A/genética , Subtipo H3N2 del Virus de la Influenza A/patogenicidad , Subtipo H3N2 del Virus de la Influenza A/fisiología , Subtipo H3N8 del Virus de la Influenza A/genética , Subtipo H3N8 del Virus de la Influenza A/patogenicidad , FemeninoRESUMEN
The rapid variation of influenza challenges vaccines and treatments, which makes an urgent task to develop the high-efficiency and low-toxicity new anti-influenza virus drugs. Selenium is one of the essential trace elements for the human body that possesses a good antiviral activity. In this study, we assessed anti-influenza A virus (H1N1) activity of polyethylene glycol (PEG)-modified gray selenium nanoparticles (PEG-SeNPs) on Madin-Darby Canine Kidney (MDCK) cells in vitro. CCK-8 assay showed that PEG-SeNPs had a protective effect on H1N1-infected MDCK cells. Moreover, PEG-SeNPs significantly reduced the mRNA level of H1N1. TUNEL-DAPI test showed that DNA damage reached a high level but effectively prevented after PEG-SeNPs treatment. Meanwhile, JC-1, Annexin V-FITC and cell cycle assay demonstrated the apoptosis induced by H1N1 was reduced greatly when treated with PEG-SeNPs. Furthermore, the downregulation of p-ATM, p-ATR and P53 protein, along with the upregualation of AKT protein indicated that PEG-SeNPs could inhibit H1N1-induced cell apoptosis through reactive oxygen species (ROS)-mediated related signaling pathways. Finally, Cytokine detection demonstrated PEG-SeNPs inhibited the production of pro-inflammatory factors after infection, including IL-1ß, IL-5, IL-6, and TNF-α. To sum up, PEG-SeNPs might become a new potential anti-H1N1 influenza virus drug due to its antiviral and anti-inflammatory activity.
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Apoptosis , Subtipo H1N1 del Virus de la Influenza A , Polietilenglicoles , Subtipo H1N1 del Virus de la Influenza A/efectos de los fármacos , Animales , Apoptosis/efectos de los fármacos , Perros , Células de Riñón Canino Madin Darby , Polietilenglicoles/química , Polietilenglicoles/farmacología , Inflamación/tratamiento farmacológico , Antivirales/farmacología , Selenio/farmacología , Selenio/química , Especies Reactivas de Oxígeno/metabolismo , Nanopartículas/química , Humanos , Daño del ADN/efectos de los fármacosRESUMEN
BACKGROUND: Swine flu might serve as a model for challenges that primary care faces during pandemics. This study examined changes in the numbers and diagnoses of general practitioner (GP) visits during and after the Swine flu pandemic in Vantaa, a Finnish city, and how GP activities recovered after the pandemic. Putative sex and age group differences were also evaluated. METHODS: The study was an observational retrospective study. The monthly number of patient visits to primary care GPs by women and men in age groups 0-19, 20-64 and 65 + years was recorded before, during and two years after the Swine flu pandemic. The recorded diagnoses were also examined. The investigation period was from 2008 to 2012. RESULTS: The numbers of monthly visits to primary care decreased from 12 324 (mean) to 10 817 in women and from 8563 to 7612 in men during the first six months of the Swine flu, returning to the original level afterwards. This decrease was thus slightly more prominent in women. However, as the size of the population increased during the follow-up period, the actual number of GP visits adjusted for the size of population remained at a decreased level for two years after the Swine flu. This decrease was observed especially in office-hours visits of men (from 3692 to 3260) and women (from 6301 to 5428) of 20-64 years. Swine flu did not alter the number of visits to the primary care Emergency Department. The proportion of visits with diagnostic recordings of common infectious diseases mostly decreased during the Swine flu. Only a minor impact on the distribution of recordings of chronic diagnoses was found. CONCLUSION: A pandemic, such as Swine flu, may decrease office-hours visits to primary care GPs. This in turn may lead to activities of primary care being adjusted downward for a long time following the pandemic. Especially the age group 20-64 years may be affected. This risk should be considered when recovery from the COVID-19 pandemic begins. Swine flu did not affect the proportion of consultations of chronic diseases, but the number of diagnoses of common infectious diseases had diminished.
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Subtipo H1N1 del Virus de la Influenza A , Gripe Humana , Pandemias , Atención Primaria de Salud , Humanos , Gripe Humana/epidemiología , Femenino , Masculino , Persona de Mediana Edad , Finlandia/epidemiología , Adulto , Estudios Retrospectivos , Adolescente , Adulto Joven , Niño , Lactante , Anciano , Preescolar , Atención Primaria de Salud/estadística & datos numéricos , Visita a Consultorio Médico/estadística & datos numéricos , Recién Nacido , Factores de Edad , Factores Sexuales , Médicos Generales/estadística & datos numéricosRESUMEN
BACKGROUND: Influenza A (H1N1) is a contagious respiratory infection caused by the influenza A virus. In the majority of cases, H1N1 influenza is benign. However, it can be dangerous for infants and children with underlying chronic diseases. The severity of influenza depends on various factors, including the virulence of the virus strain, preexisting immunity level, and individual health conditions. The aim of this study is to describe the clinical profile of H1N1 influenza in hospitalized infants and children. METHODS: This is a prospective and descriptive study conducted from November 1, 2018, to January 31, 2024. In this study, we included all children under 14 years old hospitalized for suspected severe lower respiratory infection who had gone through virological testing. We used a multiplex polymerase chain reaction (PCR) kit: the Film Array-Respiratory Panel. Due to the depletion of multiplex PCR kits, this study continued using rapid influenza diagnostic tests based on immunochromatographic technique. RESULTS: We report 45 confirmed cases of H1N1 influenza, collected during the period from November 1, 2018, to January 31, 2024. The average age was 2 years and 4 months. The main reason for admission was respiratory distress found in all patients. In 53% of the cases, there was an associated comorbidity, including asthma (17 cases), prematurity (2 cases), congenital adrenal hyperplasia (2 cases), cystic fibrosis (1 case), undetermined etiology bronchial dilation (1 case), and Basedow's disease (1 case). The clinical presentation included viral bronchiolitis (17 cases), moderate asthma exacerbation (10 cases), severe asthma exacerbation (7 cases), pneumonia (9 cases), bronchial dilation exacerbation (1 case), and flu-like syndrome with adrenal insufficiency (1 case). Fever was present in 31 patients. Gastrointestinal symptoms such as diarrhea and vomiting were present in 20 cases. Three patients required intensive care, with 2 children being intubated and ventilated (one severe acute asthma and one severe viral bronchiolitis). Two cases were treated with oseltamivir. The average length of hospital stay was 7.5 days, ranging from 3 to 20 days. All cases showed favorable evolution. CONCLUSIONS: We conclude that preventive measures remain crucial, and influenza vaccination is highly recommended in cases of underlying morbidity.
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Subtipo H1N1 del Virus de la Influenza A , Gripe Humana , Humanos , Subtipo H1N1 del Virus de la Influenza A/genética , Subtipo H1N1 del Virus de la Influenza A/aislamiento & purificación , Gripe Humana/diagnóstico , Gripe Humana/virología , Gripe Humana/epidemiología , Gripe Humana/complicaciones , Preescolar , Femenino , Masculino , Lactante , Estudios Prospectivos , Niño , Hospitalización , Adolescente , Niño Hospitalizado , Antivirales/uso terapéuticoRESUMEN
Mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) have shown anti-inflammatory potential in multiple inflammatory diseases. In the March 2022 issue of the Journal of Extracellular Vesicles, it was shown that EVs from human MSCs can suppress severe acute respiratory distress syndrome, coronavirus 2 (SARS-CoV-2) replication and can mitigate the production and release of infectious virions. We therefore hypothesized that MSC-EVs have an anti-viral effect in SARS-CoV-2 infection in vivo. We extended this question to ask whether also other respiratory viral infections could be treated by MSC-EVs. Adipose stem cell-derived EVs (ASC-EVs) were isolated using tangential flow filtration from conditioned media obtained from a multi-flask cell culture system. The effects of the ASC-EVs were tested in Vero E6 cells in vitro. ASC-EVs were also given i.v. to SARS-CoV-2 infected Syrian Hamsters, and H1N1 influenza virus infected mice. The ASC-EVs attenuated SARS-CoV-2 virus replication in Vero E6 cells and reduced body weight and signs of lung injury in infected Syrian hamsters. Furthermore, ASC-EVs increased the survival rate of influenza A-infected mice and attenuated signs of lung injury. In summary, this study suggests that ASC-EVs can have beneficial therapeutic effects in models of virus-infection-associated acute lung injury and may potentially be developed to treat lung injury in humans.
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Lesión Pulmonar Aguda , COVID-19 , Vesículas Extracelulares , Subtipo H1N1 del Virus de la Influenza A , Células Madre Mesenquimatosas , SARS-CoV-2 , Animales , Vesículas Extracelulares/metabolismo , Células Madre Mesenquimatosas/metabolismo , SARS-CoV-2/fisiología , COVID-19/terapia , Lesión Pulmonar Aguda/terapia , Lesión Pulmonar Aguda/virología , Ratones , Células Vero , Humanos , Chlorocebus aethiops , Infecciones por Orthomyxoviridae/terapia , Replicación Viral , Mesocricetus , Modelos Animales de Enfermedad , Masculino , Gripe Humana/terapia , FemeninoRESUMEN
Increased circulating tissue inhibitor of metalloproteinases-1 (TIMP-1) levels have been observed in patients with acute lung injury (ALI). However, the sex-specific regulation of TIMP-1 and the underlying molecular mechanisms have not been well elucidated. In this study, we found that plasma TIMP-1 levels were significantly higher in COVID-19 and H1N1 patients compared with those in healthy subjects (n = 25). TIMP-1 concentrations were significantly different between males and females in each disease group. Among female but not male patients, TIMP-1 levels significantly correlated with the PaO2/FiO2 ratio and hospital length of stay. Using the mouse model of ALI induced by the H1N1 virus, we found that TIMP-1 is strikingly induced in PDGFRα-positive cells in the murine lungs. Moreover, female mice showed a higher Timp-1 expression in the lungs on day 3 postinfection. Mechanistically, we observed that estrogen can upregulate TIMP-1 expression in lung fibroblasts, not epithelial cells. In addition, overexpression of estrogen receptor α (ERα) increased the TIMP-1 promoter activity. In summary, TIMP-1 is an estrogen-responsive gene, and its promoter activity is regulated by ERα. Circulating TIMP-1 may serve as a sex-specific marker, reflecting the severity and worst outcomes in female patients with SARS-CoV2- and IAV-related ALI.
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Lesión Pulmonar Aguda , Biomarcadores , COVID-19 , Receptor alfa de Estrógeno , Inhibidor Tisular de Metaloproteinasa-1 , Lesión Pulmonar Aguda/genética , Lesión Pulmonar Aguda/metabolismo , Lesión Pulmonar Aguda/sangre , Animales , Inhibidor Tisular de Metaloproteinasa-1/genética , Inhibidor Tisular de Metaloproteinasa-1/sangre , Inhibidor Tisular de Metaloproteinasa-1/metabolismo , Femenino , Masculino , Humanos , Ratones , COVID-19/metabolismo , COVID-19/genética , COVID-19/sangre , Receptor alfa de Estrógeno/metabolismo , Receptor alfa de Estrógeno/genética , Biomarcadores/sangre , Biomarcadores/metabolismo , Estrógenos/sangre , Persona de Mediana Edad , Subtipo H1N1 del Virus de la Influenza A , Pulmón/metabolismo , SARS-CoV-2 , Adulto , Regulación de la Expresión Génica , Ratones Endogámicos C57BL , Factores Sexuales , Caracteres Sexuales , Infecciones por Orthomyxoviridae/metabolismo , Infecciones por Orthomyxoviridae/sangre , Infecciones por Orthomyxoviridae/genéticaRESUMEN
The study aimed to explore the protective effect of mask use against respiratory tract viral agents during the pandemic. The study included patients with a COVID-19 negative test who were hospitalized in the pulmonary disease clinic with the diagnoses of asthma attack, chronic obstructive pulmonary disease (COPD) exacerbation, and pneumonia in two periods: during mandatory mask use (October 2021 - May 2022) and after the mask mandate was lifted (October 2022 - May 2023). Combined nose and throat swab samples taken from the patients were evaluated for viral agents by using the PCR test method. Viral agents isolated from the patients in the two periods were compared based on hospitalization diagnoses and periods. The study enrolled 1,335 patients, 483 female and 852 male. It was found that viral agents significantly increased during the period without a mask mandate compared to the period when the mask mandate was in effect (41.6% vs. 23.4%) (p < 0.001). During the period without mask mandate, influenza A, H1N1, and RSV/AB viruses significantly increased (p = 0.019, p = 0.003, p < 0.001, respectively). Our results indicated that mask use during the pandemic is protective against the transmission of respiratory tract viruses. Thus, it can be concluded that mask use is important not only in the coronavirus pandemic but also especially in influenza and RSV epidemics.
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COVID-19 , Máscaras , SARS-CoV-2 , Estaciones del Año , Humanos , Masculino , Femenino , Máscaras/virología , COVID-19/epidemiología , COVID-19/virología , COVID-19/prevención & control , Persona de Mediana Edad , SARS-CoV-2/aislamiento & purificación , Gripe Humana/virología , Gripe Humana/epidemiología , Adulto , Pacientes Internos , Anciano , Subtipo H1N1 del Virus de la Influenza A/genética , Subtipo H1N1 del Virus de la Influenza A/aislamiento & purificación , Hospitalización/estadística & datos numéricosRESUMEN
Introduction: Influenza A virus (IAV) infection is a global respiratory disease, which annually leads to 3-5 million cases of severe illness, resulting in 290,000-650,000 deaths. Additionally, during the past century, four global IAV pandemics have claimed millions of human lives. The epithelial lining of the trachea plays a vital role during IAV infection, both as point of viral entry and replication as well as in the antiviral immune response. Tracheal tissue is generally inaccessible from human patients, which makes animal models crucial for the study of the tracheal host immune response. Method: In this study, pigs were inoculated with swine- or human-adapted H1N1 IAV to gain insight into how host adaptation of IAV shapes the innate immune response during infection. In-depth multi-omics analysis (global proteomics and RNA sequencing) of the host response in upper and lower tracheal tissue was conducted, and results were validated by microfluidic qPCR. Additionally, a subset of samples was selected for histopathological examination. Results: A classical innate antiviral immune response was induced in both upper and lower trachea after infection with either swine- or human-adapted IAV with upregulation of genes and higher abundance of proteins associated with viral infection and recognition, accompanied by a significant induction of interferon stimulated genes with corresponding higher proteins concentrations. Infection with the swine-adapted virus induced a much stronger immune response compared to infection with a human-adapted IAV strain in the lower trachea, which could be a consequence of a higher viral load and a higher degree of inflammation. Discussion: Central components of the JAK-STAT pathway, apoptosis, pyrimidine metabolism, and the cytoskeleton were significantly altered depending on infection with swine- or human-adapted virus and might be relevant mechanisms in relation to antiviral immunity against putative zoonotic IAV. Based on our findings, we hypothesize that during host adaptation, IAV evolve to modulate important host cell elements to favor viral infectivity and replication.
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Infecciones por Orthomyxoviridae , Proteómica , Tráquea , Animales , Tráquea/inmunología , Tráquea/virología , Porcinos , Infecciones por Orthomyxoviridae/inmunología , Infecciones por Orthomyxoviridae/virología , Proteómica/métodos , Humanos , Adaptación al Huésped/inmunología , Inmunidad Innata , Subtipo H1N1 del Virus de la Influenza A/inmunología , Interacciones Huésped-Patógeno/inmunología , MultiómicaRESUMEN
To facilitate rapid monitoring of airborne viruses, they must be collected with high efficiency and concentrated in a small volume of a liquid sample. In addition, the development of low-cost miniaturized samplers is essential for multipoint monitoring. Thus, in an attempt to fulfill these requirements, this study developed a microfluidic condensation bioaerosol sampler (MCBS). The developed sampler comprised two parts: a virus growth section and a virus droplet-to-liquid sample conversion section, each of which was fabricated on a chip using microfluidic technology. The condensation nucleus growth technique used in the virus growth section grew nanometer-sized airborne viruses into micro-sized droplets, making it possible to collection of viruses easier and with high efficiency. In addition, the virus droplet-to-liquid sample conversion section controlled the transport of droplets based on electrowetting technology. This enabled the collected airborne viruses to be concentrated in tens of microliters of the liquid sample. To evaluate the performance of both the sections, the virus dropletization, virus collection efficiency, and virus droplet-to-liquid sample conversion efficiency were evaluated through quantitative experiments. H1N1 and HCOV-229E viruses were used to conduct quantitative experiments on MCBS. We could obtain virus liquid samples with at 72.8- and 89.9-times higher concentration through 1:1 evaluation with a commercial sampler. Thus, the developed sampler facilitated efficient collection and concentration of airborne viruses in a compact, cost-effective manner. This is expected to facilitate rapid and accurate multipoint monitoring of viral aerosols.
Asunto(s)
Aerosoles , Microbiología del Aire , Técnicas Biosensibles , Diseño de Equipo , Aerosoles/análisis , Técnicas Biosensibles/instrumentación , Humanos , Dispositivos Laboratorio en un Chip , Microfluídica/instrumentación , Subtipo H1N1 del Virus de la Influenza A/aislamiento & purificación , Monitoreo del Ambiente/instrumentación , Monitoreo del Ambiente/métodos , Técnicas Analíticas Microfluídicas/instrumentaciónRESUMEN
Sporadically and periodically, influenza outbreaks threaten global health and the economy. Antigen drift-induced influenza virus mutations hamper antiviral drug development. Thus, a novel antiviral agent is urgently needed to address medication inefficacy issues. Herein, sixteen new quinoline-triazole hybrids 6a-h and 9a-h were prepared and evaluated in vitro against the H1N1 virus. In particular, 6d, 6e, and 9b showed promising H1N1 antiviral activity with selective index (SI) CC50/IC50 values of 15.8, 37, and 29.15. After that, the inhibition rates for various mechanisms of action (virus replication, adsorption, and virucidal activity) were investigated for the most efficient candidates 6d, 6e, and 9b. Additionally, their ability to inhibit neuraminidase was evaluated. With an IC50 value of 0.30 µM, hybrid 6d demonstrated effective and comparable inhibitory activity to Oseltamivir. Ultimately, molecular modeling investigations, encompassing molecular docking and molecular dynamic simulations, were conducted to provide a scientific basis for the observed antiviral results.
Asunto(s)
Antivirales , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos , Subtipo H1N1 del Virus de la Influenza A , Neuraminidasa , Quinolinas , Triazoles , Subtipo H1N1 del Virus de la Influenza A/efectos de los fármacos , Subtipo H1N1 del Virus de la Influenza A/enzimología , Antivirales/farmacología , Antivirales/química , Antivirales/síntesis química , Quinolinas/química , Quinolinas/farmacología , Quinolinas/síntesis química , Neuraminidasa/antagonistas & inhibidores , Neuraminidasa/metabolismo , Triazoles/química , Triazoles/farmacología , Triazoles/síntesis química , Relación Estructura-Actividad , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/síntesis química , Estructura Molecular , Humanos , Pruebas de Sensibilidad Microbiana , Descubrimiento de Drogas , Simulación del Acoplamiento MolecularRESUMEN
Sensitive, convenient and rapid detection and subtyping of influenza viruses are crucial for timely treatment and management of infected people. Compared with antigen detection, nucleic acid detection has higher specificity and can shorten the detection window. Hence, in this work, we improved the lateral flow assay (LFA, one of the most promising user-friendly and on-site methods) to achieve detection and subtyping of H1N1, H3N2 and H9N2 influenza virus nucleic acids. Firstly, the antigen-antibody recognition mode was transformed into a nucleic acid hybridization reaction. Secondly, Fe3O4-Au heterodimer nanoparticles were prepared to replace frequently used Au nanoparticles to obtain better coloration. Thirdly, four lines were arranged on the LFA strip, which were three test (T) lines and one control (C) line. Three T lines were respectively sprayed by the DNA sequences complementary to one end of H1N1, H3N2 and H9N2 influenza virus nucleic acids, while Fe3O4-Au nanoparticles were respectively coupled with the DNA sequences complementary to the other end of H1N1, H3N2 and H9N2 nucleic acids to construct three kinds of probes. The C line was sprayed by the complementary sequences to the DNAs on all three kinds of probes. In the detection, by hybridization reaction, the probes were combined with their target nucleic acids which were captured by the corresponding T lines to form color bands. Finally, according to the position of the color bands and their grey intensity, simultaneous qualitative and semi-quantitative detection of the three influenza virus nucleic acids was realized. The detection results showed that this multi-channel LFA had good specificity, and there was no significant cross reactivity among the three subtypes of influenza viruses. The simultaneous detection achieved comparable detection limits with individual detections. Therefore, this multi-channel LFA had good application potential for sensitive and rapid detection and subtyping of influenza viruses.
Asunto(s)
Oro , Oro/química , Humanos , Subtipo H3N2 del Virus de la Influenza A/química , Subtipo H3N2 del Virus de la Influenza A/aislamiento & purificación , Nanopartículas del Metal/química , Subtipo H1N1 del Virus de la Influenza A/aislamiento & purificación , Subtipo H1N1 del Virus de la Influenza A/química , Subtipo H1N1 del Virus de la Influenza A/inmunología , Subtipo H9N2 del Virus de la Influenza A/química , Subtipo H9N2 del Virus de la Influenza A/aislamiento & purificación , Hibridación de Ácido Nucleico/métodos , ADN Viral/análisis , Gripe Humana/diagnóstico , Nanopartículas de Magnetita/química , Límite de DetecciónRESUMEN
The similar transmission patterns and early symptoms of respiratory viral infections, particularly severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza (H1N1), and respiratory syncytial virus (RSV), pose substantial challenges in the diagnosis, therapeutic management, and handling of these infectious diseases. Multiplexed point-of-care testing for detection is urgently needed for prompt and efficient disease management. Here, we introduce an electrochemical paper-based analytical device (ePAD) platform for multiplexed and label-free detection of SARS-CoV-2, H1N1, and RSV infection using immobilized pyrrolidinyl peptide nucleic acid probes. Hybridization between the probes and viral nucleic acid targets causes changes in the electrochemical response. The resulting sensor offers high sensitivity and low detection limits of 0.12, 0.35, and 0.36 pM for SARS-CoV-2 (N gene), H1N1, and RSV, respectively, without showing any cross-reactivities. The amplification-free detection of extracted RNA from 42 nasopharyngeal swab samples was successfully demonstrated and validated against reverse-transcription polymerase chain reaction (range of cycle threshold values: 17.43-25.89). The proposed platform showed excellent clinical sensitivity (100 %) and specificity (≥97 %) to achieve excellent agreement (κ ≥ 0.914) with the standard assay, thereby demonstrating its applicability for the screening and diagnosis of these respiratory diseases.
Asunto(s)
Técnicas Biosensibles , Técnicas Electroquímicas , Subtipo H1N1 del Virus de la Influenza A , Papel , Ácidos Nucleicos de Péptidos , SARS-CoV-2 , Técnicas Biosensibles/métodos , Subtipo H1N1 del Virus de la Influenza A/aislamiento & purificación , Subtipo H1N1 del Virus de la Influenza A/genética , Técnicas Electroquímicas/métodos , Humanos , SARS-CoV-2/aislamiento & purificación , SARS-CoV-2/genética , Ácidos Nucleicos de Péptidos/química , COVID-19/diagnóstico , COVID-19/virología , ARN Viral/análisis , ARN Viral/genética , Infecciones por Virus Sincitial Respiratorio/diagnóstico , Infecciones por Virus Sincitial Respiratorio/virología , Límite de Detección , Gripe Humana/diagnóstico , Gripe Humana/virología , Virus Sincitiales Respiratorios/aislamiento & purificación , Virus Sincitiales Respiratorios/genética , Virus Sincitial Respiratorio Humano/aislamiento & purificación , Virus Sincitial Respiratorio Humano/genéticaRESUMEN
Influenza viruses are susceptible to seasonal influenza, which has repeatedly caused global pandemics and jeopardized human health. Vaccines are only used as preventive medicine due to the extreme mutability of influenza viruses, and antiviral medication is the most significant clinical treatment to reduce influenza morbidity and mortality. Nevertheless, the clinical application of anti-influenza virus agents is characterized by the narrow therapeutic time window, the susceptibility to drug resistance, and relatively limited effect on severe influenza. Therefore, it is of great significance to develop novel anti-influenza virus drugs to fulfill the urgent clinical needs. Influenza viruses enter host cells through the hemagglutinin (HA) mediated membrane fusion process, and fusion inhibitors function antivirally by blocking hemagglutinin deformation, promising better therapeutic efficacy and resolving drug resistance, with targets different from marketed medicines. Previous studies have shown that unnatural peptides derived from Human Immunodeficiency Virus Type 1 (HIV-1) membrane fusion proteins exhibit anti-HIV-1 activity. Based on the similarity of the membrane fusion protein deformation process between HIV-1 and H1N1, we selected sequences derived from the gp41 subunit in the HIV-1 fusion protein, and then constructed N-trimer spatial structure through inter-helical isopeptide bond modification, to design the novel anti-H1N1 fusion inhibitors. The results showed that the novel peptides could block 6-HB formation during H1N1 membrane fusion procedure, and thus possessed significant anti-H1N1 activity, comparable to the positive control oseltamivir. Our study demonstrates the design viability of peptide fusion inhibitors based on similar membrane fusion processes among viruses, and furthermore provides an important idea for the novel anti-H1N1 inhibitors development.
Asunto(s)
Antivirales , Subtipo H1N1 del Virus de la Influenza A , Péptidos , Subtipo H1N1 del Virus de la Influenza A/efectos de los fármacos , Antivirales/farmacología , Antivirales/química , Antivirales/síntesis química , Humanos , Péptidos/química , Péptidos/farmacología , Péptidos/síntesis química , Pruebas de Sensibilidad Microbiana , Relación Estructura-Actividad , Células de Riñón Canino Madin Darby , Perros , Relación Dosis-Respuesta a Droga , Animales , Estructura Molecular , Secuencia de AminoácidosRESUMEN
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has triggered an ongoing global pandemic, necessitating rapid and accurate diagnostic tools to monitor emerging variants and preparedness for the next outbreak. This study introduces a multidisciplinary approach combining Fourier Transform Infrared (FTIR) microspectroscopy and Machine learning to comprehensively characterize and strain-type SARS-CoV-2 variants. FTIR analysis of pharyngeal swabs from different pandemic waves revealed distinct vibrational profiles, particularly in nucleic acid and protein vibrations. The spectral wavenumber range between 1150 and 1240 cm-1 was identified as the classification marker, distinguishing Healthy (noninfected) and infected samples. Machine learning algorithms, with neural networks exhibiting superior performance, successfully classified SARS-CoV-2 variants with a remarkable accuracy of 98.6%. Neural networks were also able to identify and differentiate a small cohort infected with influenza A variants, H1N1 and H3N2, from SARS-CoV-2-infected and Healthy samples. FTIR measurements further show distinct red shifts in vibrational energy and secondary structural alterations in the spike proteins of more transmissible forms of SARS-CoV-2 variants, providing experimental validation of the computational data. This integrated approach presents a promising avenue for rapid and reliable SARS-CoV-2 variant identification, enhancing our understanding of viral evolution and aiding in diagnostic advancements, particularly for an infectious disease with unknown etiology.
Asunto(s)
COVID-19 , SARS-CoV-2 , Espectroscopía Infrarroja por Transformada de Fourier/métodos , SARS-CoV-2/aislamiento & purificación , SARS-CoV-2/genética , SARS-CoV-2/química , Humanos , COVID-19/diagnóstico , COVID-19/virología , Subtipo H1N1 del Virus de la Influenza A/aislamiento & purificación , Subtipo H1N1 del Virus de la Influenza A/genética , Glicoproteína de la Espiga del Coronavirus/química , Aprendizaje Automático , Subtipo H3N2 del Virus de la Influenza A/aislamiento & purificación , Subtipo H3N2 del Virus de la Influenza A/genética , Redes Neurales de la ComputaciónRESUMEN
Orally dissolving films (ODF) are designed to be dissolved on the tongue and absorbed in the mouth. It offers multiple advantages over the commonly used needle-based vaccines, especially in terms of convenience allowing safe, painless, and easy self-administration. As the efficacy of ODF-encapsulated influenza vaccines has not been demonstrated, we assessed the protection elicited by inactivated influenza virus (A/PR/8/34, H1N1) vaccine delivered using ODFs in mice. Trehalose and pullulan components of the ODF ensured that the HA antigens of the inactivated PR8 virus retained their stability while ensuring the rapid release of the vaccines upon exposure to murine saliva. Mice were immunized thrice by placing the PR8-ODF on the tongues of mice at 4-week intervals, and vaccine-induced protection was evaluated upon lethal homologous challenge infection. The PR8-ODF vaccination elicited virus-specific serum IgG and IgA antibody responses, hemagglutinin inhibition (HAI), and viral neutralization. Upon challenge infection, ODF vaccination showed higher levels of IgG and IgA antibody responses in the lungs and antibody-secreting cell (ASC) responses in both lung and spleen compared to unimmunized controls. These results corresponded with the enhanced T cell and germinal center B cell responses in the lungs and spleens. Importantly, ODF vaccination significantly reduced lung virus titers and inflammatory cytokines (IFN-γ, IL-6) production compared to unvaccinated control. ODF vaccination ensured 100% survival and prevented weight loss in mice. These findings suggest that influenza vaccine delivery through ODFs could be a promising approach for oral vaccine development.