RESUMEN
After the termination of zero-COVID-19 policy, the populace in China has experienced both Omicron BA.5 and XBB waves. Considering the poor antibody responses and severe outcomes observed among the elderly following infection, we conducted a longitudinal investigation to examine the epidemiological characteristics and antibody kinetics among 107 boosted elderly participants following the Omicron BA.5 and XBB waves. We observed that 96 participants (89.7%) were infected with Omicron BA.5, while 59 (55.1%) participants were infected with Omicron XBB. Notably, 52 participants (48.6%) experienced dual infections of both Omicron BA.5 and XBB. The proportion of symptomatic cases appeared to decrease following the XBB wave (18.6%) compared to that after the BA.5 wave (59.3%). Omicron BA.5 breakthrough infection induced lower neutralizing antibody titers against XBB.1.5, BA.2.86, and JN.1, while reinfection with Omicron XBB broadened the antibody responses against all measured Omicron subvariants and may alleviate the wild type-vaccination induced immune imprinting. Boosted vaccination type and comorbidities were the significant factors associated with antibody responses. Updated vaccines based on emerging severe acute respiratory syndrome coronavirus 2 variants are needed to control the Coronavirus Disease 2019 pandemic in the elderly.
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Vacunas contra la COVID-19 , COVID-19 , Inmunización Secundaria , SARS-CoV-2 , Humanos , Anciano , COVID-19/epidemiología , COVID-19/inmunología , COVID-19/virología , Vacunas contra la COVID-19/administración & dosificación , Masculino , Femenino , Estudios Longitudinales , China/epidemiología , SARS-CoV-2/clasificación , SARS-CoV-2/fisiología , Anticuerpos Neutralizantes , Cinética , Anticuerpos Antivirales/sangre , Reinfección/epidemiologíaRESUMEN
The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariants raises concerns regarding the effectiveness of immunity acquired from previous Omicron subvariants breakthrough infections (BTIs) or reinfections (RIs) against the current circulating Omicron subvariants. In this study, we prospectively investigate the dynamic changes of virus-specific antibody and T cell responses among 77 adolescents following Omicron BA.2.3 BTI with or without subsequent Omicron BA.5 RI. Notably, the neutralizing antibodies (NAbs) titers against various detected SARS-CoV-2 variants, especially the emerging Omicron CH.1.1, XBB.1.5, XBB.1.16, EG.5.1, and JN.1 subvariants, exhibited a significant decrease along the time. A lower level of IgG and NAbs titers post-BTI was found to be closely associated with subsequent RI. Elevated NAbs levels and shortened antigenic distances were observed following Omicron BA.5 RI. Robust T cell responses against both Omicron BA.2- and CH.1.1-spike peptides were observed at each point visited. The exposure to Omicron BA.5 promoted phenotypic differentiation of virus-specific memory T cells, even among the non-seroconversion adolescents. Therefore, updated vaccines are needed to provide effective protection against newly emerging SARS-CoV-2 variants among adolescents.
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Anticuerpos Neutralizantes , Anticuerpos Antivirales , COVID-19 , Células T de Memoria , Reinfección , SARS-CoV-2 , Humanos , Adolescente , COVID-19/inmunología , COVID-19/virología , SARS-CoV-2/inmunología , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Anticuerpos Neutralizantes/inmunología , Anticuerpos Neutralizantes/sangre , Masculino , Reinfección/inmunología , Reinfección/virología , Femenino , Células T de Memoria/inmunología , Estudios Prospectivos , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Formación de Anticuerpos , Glicoproteína de la Espiga del Coronavirus/inmunología , Memoria Inmunológica , Niño , Linfocitos T/inmunologíaRESUMEN
Rodents and shrews are major reservoirs of various pathogens that are related to zoonotic infectious diseases. The purpose of this study was to investigate co-infections of zoonotic pathogens in rodents and shrews trapped in four provinces of China. We sampled different rodent and shrew communities within and around human settlements in four provinces of China and characterised several important zoonotic viral, bacterial, and parasitic pathogens by PCR methods and phylogenetic analysis. A total of 864 rodents and shrews belonging to 24 and 13 species from RODENTIA and EULIPOTYPHLA orders were captured, respectively. For viral pathogens, two species of hantavirus (Hantaan orthohantavirus and Caobang orthohantavirus) were identified in 3.47% of rodents and shrews. The overall prevalence of Bartonella spp., Anaplasmataceae, Babesia spp., Leptospira spp., Spotted fever group Rickettsiae, Borrelia spp., and Coxiella burnetii were 31.25%, 8.91%, 4.17%, 3.94%, 3.59%, 3.47%, and 0.58%, respectively. Furthermore, the highest co-infection status of three pathogens was observed among Bartonella spp., Leptospira spp., and Anaplasmataceae with a co-infection rate of 0.46%. Our results suggested that species distribution and co-infections of zoonotic pathogens were prevalent in rodents and shrews, highlighting the necessity of active surveillance for zoonotic pathogens in wild mammals in wider regions.
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Bartonella , Coinfección , Leptospira , Animales , Bartonella/genética , China/epidemiología , Filogenia , Roedores/microbiología , Musarañas/microbiologíaRESUMEN
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron (B.1.1.529) variant extensively escape neutralizing antibodies by vaccines or infection. We assessed serum neutralizing activity in sera from Delta infection after vaccination and Delta infection only against SARS-CoV-2 Wuhan-Hu-1 (WA1), Beta, Delta, and Omicron. Sera from Delta infection only could neutralize WA1 and Delta but almost completely lost capacity to neutralize Beta and Omicron. However, Delta infection after vaccination resulted in a significant increase of serum neutralizing activity against WA1, Beta, and Omicron. This study demonstrates that breakthrough infection of Delta substantially induced high potency humoral immune response against the Omicron variant and other emerged variants.
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Anticuerpos Neutralizantes , Vacunas contra la COVID-19 , COVID-19 , Inmunidad Humoral , Humanos , Anticuerpos Antivirales , COVID-19/inmunología , COVID-19/prevención & control , Pruebas de Neutralización , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , Vacunación , Vacunas contra la COVID-19/inmunologíaRESUMEN
The severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) survivors are more likely to produce a potent immune response to SARS-CoV-2 after booster vaccination. We assessed humoral and T cell responses against SARS-CoV-2 in previously vaccinated SARS-CoV-1 survivors and naïve healthy individuals (NHIs) after a booster Ad5-nCoV dose. Boosted SARS-CoV-1 survivors had a high neutralization of SARS-CoV-2 Wuhan-Hu-1 (WA1), Beta, and Delta but is limited to Omicron subvariants (BA.1, BA.2, BA.2.12.1, and BA.4/BA.5). Most boosted SARS-CoV-1 survivors had robust SARS-CoV-2-specific CD4+ and CD8+ T cell responses. While booster vaccination in NHIs elicited less or ineffective neutralization of WA1, Beta, and Delta, and none of them induced neutralizing antibodies against Omicron subvariants. However, they developed comparable SARS-CoV-2-specific T cell responses compared to boosted SARS-CoV-1 survivors. These findings suggest that boosted Ad5-nCoV would not elicit effective neutralizing antibodies against Omicron subvariants in SARS-CoV-1 survivors and NHIs but induced comparable robust T cell responses. Achieving a high antibody titer in SARS-CoV-1 survivors and NHIs is desirable to generate broad neutralization.
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Vacunas contra el SIDA , COVID-19 , Vacunas contra la Influenza , Vacunas contra Papillomavirus , Vacunas contra Virus Sincitial Respiratorio , Vacunas contra el SIDAS , Anticuerpos Neutralizantes , Anticuerpos Antivirales , Vacuna BCG , Vacunas contra la COVID-19 , Vacuna contra Difteria, Tétanos y Tos Ferina , Humanos , Vacuna contra el Sarampión-Parotiditis-Rubéola , SARS-CoV-2 , SobrevivientesRESUMEN
BACKGROUND: The duration of humoral and T and B cell response after the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains unclear. METHODS: We performed a cross-sectional study to assess the virus-specific antibody and memory T and B cell responses in coronavirus disease 2019 (COVID-19) patients up to 343 days after infection. Neutralizing antibodies and antibodies against the receptor-binding domain, spike, and nucleoprotein of SARS-CoV-2 were measured. Virus-specific memory T and B cell responses were analyzed. RESULTS: We enrolled 59 patients with COVID-19, including 38 moderate, 16 mild, and 5 asymptomatic patients; 31 (52.5%) were men and 28 (47.5%) were women. The median age was 41 years (interquartile range, 30-55). The median day from symptom onset to enrollment was 317 days (range 257 to 343 days). We found that approximately 90% of patients still have detectable immunoglobulin (Ig)G antibodies against spike and nucleocapsid proteins and neutralizing antibodies against pseudovirus, whereas ~60% of patients had detectable IgG antibodies against receptor-binding domain and surrogate virus-neutralizing antibodies. The SARS-CoV-2-specific IgG+ memory B cell and interferon-γ-secreting T cell responses were detectable in more than 70% of patients. CONCLUSIONS: Severe acute respiratory syndrome coronavirus 2-specific immune memory response persists in most patients approximately 1 year after infection, which provides a promising sign for prevention from reinfection and vaccination strategy.
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Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , COVID-19/inmunología , Inmunidad Celular/inmunología , Adulto , Linfocitos B/inmunología , Estudios Transversales , Femenino , Humanos , Inmunoglobulina G/inmunología , Memoria Inmunológica/inmunología , Masculino , Persona de Mediana Edad , Proteínas de la Nucleocápside/inmunología , SARS-CoV-2/inmunología , Glicoproteína de la Espiga del Coronavirus/inmunología , Linfocitos T/inmunologíaRESUMEN
We quantified the serum levels of 34 cytokines/chemokines in 30 patients with SARS-CoV-2 infection. Elevated levels of IP-10 and IL-7 were detected in the acute and convalescent stages of the infection and were highly associated with disease severity.
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COVID-19/sangre , Quimiocina CXCL10/sangre , Interleucina-7/sangre , SARS-CoV-2/metabolismo , Índice de Severidad de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Data concerning the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in asymptomatic and paucisymptomatic patients are lacking. We report a 3-family cluster of infections involving asymptomatic and paucisymptomatic transmission. Eight of 15 (53%) members from 3 families were confirmed with SARS-CoV-2 infection. Of 8 patients, 3 were asymptomatic and 1 was paucisymptomatic. An asymptomatic mother transmitted the virus to her son, and a paucisymptomatic father transmitted the virus to his 3-month-old daughter. SARS-CoV-2 was detected in the environment of 1 household. The complete genomes of SARS-CoV-2 from the patients were > 99.9% identical and were clustered with other SARS-CoV-2 sequences reported from China and other countries.
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Infecciones Asintomáticas , Infecciones por Coronavirus/transmisión , Neumonía Viral/transmisión , Adulto , Anciano , Betacoronavirus/genética , COVID-19 , China/epidemiología , Trazado de Contacto , Infecciones por Coronavirus/epidemiología , Salud de la Familia , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Pandemias , Filogenia , Neumonía Viral/epidemiología , Cuarentena , SARS-CoV-2RESUMEN
BACKGROUND: China is thought to be a hotspot for zoonotic influenza virus emergence, yet there have been few prospective studies examining the occupational risks of such infections. METHODS: We present the first 2 years of data collected from a 5-year, prospective, cohort study of swine-exposed and -unexposed participants at 6 swine farms in China. We conducted serological and virological surveillance to examine evidence for swine influenza A virus infection in humans. RESULTS: Of the 658 participants (521 swine-exposed and 137 swine-unexposed), 207 (31.5%) seroconverted against at least 1 swine influenza virus subtype (swine H1N1 or H3N2). Swine-exposed participants' microneutralization titers, especially those enrolled at confined animal feeding operations (CAFOs), were higher against the swine H1N1 virus than were other participants at 12 and 24 months. Despite elevated titers, among the 187 study subjects for whom we had complete follow-up, participants working at swine CAFOs had significantly greater odds of seroconverting against both the swine H1N1 (odds ratio [OR] 19.16, 95% confidence interval [CI] 3.55-358.65) and swine H3N2 (OR 2.97, 95% CI 1.16-8.01) viruses, compared to unexposed and non-CAFO swine workers with less intense swine exposure. CONCLUSIONS: While some of the observed increased risk against swine viruses may have been explained by exposure to human influenza strains, study data suggest that even with elevated preexisting antibodies, swine-exposed workers were at high risk of infection with enzootic swine influenza A viruses.
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Subtipo H1N1 del Virus de la Influenza A , Gripe Humana , Infecciones por Orthomyxoviridae , Enfermedades de los Porcinos , Animales , Anticuerpos Antivirales , China/epidemiología , Estudios de Cohortes , Subtipo H3N2 del Virus de la Influenza A , Gripe Humana/epidemiología , Infecciones por Orthomyxoviridae/epidemiología , Infecciones por Orthomyxoviridae/veterinaria , Estudios Prospectivos , Estudios Seroepidemiológicos , Porcinos , Enfermedades de los Porcinos/epidemiología , Zoonosis/epidemiologíaAsunto(s)
Anticuerpos Neutralizantes/inmunología , Vacunas contra la COVID-19/inmunología , COVID-19/prevención & control , SARS-CoV-2/inmunología , Anticuerpos Neutralizantes/sangre , Anticuerpos Antivirales/sangre , COVID-19/inmunología , Reacciones Cruzadas , Farmacorresistencia Viral , Humanos , Técnicas Microbiológicas , Mutación , Pruebas de Neutralización , SARS-CoV-2/genética , Glicoproteína de la Espiga del Coronavirus/genética , Estomatitis/virología , Vacunas de Productos Inactivados/inmunologíaRESUMEN
Background: Our understanding of influenza A virus transmission between humans and pigs is limited. Methods: Beginning in 2015, we used a One Health approach and serial sampling to prospectively study 299 swine workers and 100 controls, their 9000 pigs, and 6 pig farm environments in China for influenza A viruses (IAVs) using molecular, culture, and immunological techniques. Study participants were closely monitored for influenza-like illness (ILI) events. Results: Upon enrollment, swine workers had higher serum neutralizing antibody titers against swine H1N1 and higher nasal wash total immunoglobulin A (IgA) and specific IgA titers against swine H1N1 and H3N2 viruses. Over a period of 12 months, IAVs were detected by quantitative reverse-transcription polymerase chain reaction in 46 of 396 (11.6%) environmental swabs, 235 of 3300 (7.1%) pig oral secretion, 23 of 396 (5.8%) water, 20 of 396 (5.1%) aerosol, and 19 of 396 (4.8%) fecal-slurry specimens. Five of 32 (15.6%) participants with ILI events had nasopharyngeal swab specimens that were positive for IAV, and 17 (53.1%) demonstrated 4-fold rises in neutralization titers against a swine virus. Reassorted Eurasian avian-lineage H1N1, A(H1N1)pdm09-like, and swine-lineage H3N2 viruses were identified in pig farms. The A(H1N1)pdm09-like H1N1 viruses identified in swine were nearly genetically identical to the human H1N1 viruses isolated from the participants with ILI. Conclusions: There was considerable evidence of A(H1N1)pdm09-like, swine-lineage H1N1, and swine-lineage H3N2 viruses circulating, likely reassorting, and likely crossing species within the pig farms. These data suggest that stronger surveillance for novel influenza virus emergence within swine farms is imperative.
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Gripe Humana/transmisión , Infecciones por Orthomyxoviridae/transmisión , Virus Reordenados/patogenicidad , Enfermedades de los Porcinos/transmisión , Adolescente , Adulto , Anciano , Animales , Anticuerpos Neutralizantes/sangre , Anticuerpos Antivirales/sangre , Agricultores , Granjas/estadística & datos numéricos , Femenino , Humanos , Inmunidad Mucosa , Subtipo H1N1 del Virus de la Influenza A , Subtipo H3N2 del Virus de la Influenza A , Masculino , Persona de Mediana Edad , Salud Única , Infecciones por Orthomyxoviridae/inmunología , Estudios Prospectivos , Factores de Riesgo , Porcinos/virología , Zoonosis/transmisiónRESUMEN
We conducted a 3-year longitudinal serologic survey on an open cohort of poultry workers, swine workers, and general population controls to assess avian influenza A virus (AIV) seroprevalence and seroincidence and virologic diversity at live poultry markets (LPMs) in Wuxi City, Jiangsu Province, China. Of 964 poultry workers, 9 (0.93%) were seropositive for subtype H7N9 virus, 18 (1.87%) for H9N2, and 18 (1.87%) for H5N1. Of 468 poultry workers followed longitudinally, 2 (0.43%), 13 (2.78%), and 7 (1.5%) seroconverted, respectively; incidence was 1.27, 8.28, and 4.46/1,000 person-years for H7N9, H9N2, and H5N1 viruses, respectively. Longitudinal surveillance of AIVs at 9 LPMs revealed high co-circulation of H9, H7, and H5 subtypes. We detected AIVs in 726 (23.3%) of 3,121 samples and identified a high diversity (10 subtypes) of new genetic constellations and reassortant viruses. These data suggest that stronger surveillance for AIVs within LPMs and high-risk populations is imperative.
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Agricultores , Virus de la Influenza A , Gripe Humana/epidemiología , Gripe Humana/virología , Adulto , Anciano , Animales , China/epidemiología , Femenino , Geografía , Historia del Siglo XXI , Humanos , Incidencia , Virus de la Influenza A/clasificación , Virus de la Influenza A/genética , Gripe Aviar/virología , Gripe Humana/historia , Gripe Humana/transmisión , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Aves de Corral/virología , Vigilancia en Salud Pública , Factores de Riesgo , Estudios Seroepidemiológicos , PorcinosRESUMEN
Avian influenza A(H7N9) virus has caused 5 epidemic waves in China since its emergence in 2013. We investigated the dynamic changes of antibody response to this virus over 1 year postinfection in 25 patients in Suzhou City, Jiangsu Province, China, who had laboratory-confirmed infections during the fifth epidemic wave, October 1, 2016-February 14, 2017. Most survivors had relatively robust antibody responses that decreased but remained detectable at 1 year. Antibody response was variable; several survivors had low or undetectable antibody titers. Hemagglutination inhibition titer was >1:40 for <40% of the survivors. Measured in vitro in infected mice, hemagglutination inhibition titer predicted serum protective ability. Our findings provide a helpful serologic guideline for identifying subclinical infections and for developing effective vaccines and therapeutics to counter H7N9 virus infections.
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Anticuerpos Antivirales/inmunología , Subtipo H7N9 del Virus de la Influenza A/inmunología , Gripe Humana/epidemiología , Gripe Humana/inmunología , Anciano , Animales , Anticuerpos Antivirales/sangre , Femenino , Historia del Siglo XXI , Hospitalización , Humanos , Subtipo H7N9 del Virus de la Influenza A/clasificación , Gripe Humana/historia , Gripe Humana/virología , Masculino , Ratones , Persona de Mediana Edad , Pruebas Serológicas , SobrevivientesRESUMEN
Critical and major operations are often accompanied by brain ischemic complications. Previous studies found that propofol post-conditioning provided neuroprotective functions through upregulating the expression of potassium chloride cotransporter 2 (KCC2) in gamma-aminobutyric acid (GABA) interneurons. Membrane expression and phosphorylation represents KCC2 activity, which were modulated by a protein kinase C (PKC)-dependent mechanism. However, the role of propofol in increasing KCC2 phosphorylation and the involvement of protein kinase Mζ (PKMζ), a major subtype of PKC, in the KCC2 pathway remained unclear. In this study, we established middle cerebral artery occlusion model in rats to evaluate the long-term recovery of brain functions using behavioral experiments. KCC2 and PKMζ were assessed via western blot. We used the selective inhibitor, zeta inhibitory peptide (ZIP), to investigate the relationship between KCC2 and PKMζ. Intracellular chloride concentration in the hippocampal CA1 area was measured to determine KCC2 activity. We found that propofol, infused at a speed of 20 mg kg-1 h-1 for 2 h at the onset of reperfusion, improved neurological deficits and cognitive dysfunction following ischemia/reperfusion injury. PKMζ expression was significantly upregulated, which improved KCC2 membrane expression and phosphorylation in the ischemic hippocampal CA1 area, and these effects could last up to 28 days. But ZIP inhibited this process. Ultimately, we showed that propofol increased KCC2 phosphorylation and PKMζ was the upstream of KCC2. Propofol led to long-term recovery of brain functions by upregulating the activity of the PKMζ/KCC2 pathway.
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Neuroprotección/efectos de los fármacos , Propofol/farmacología , Proteína Quinasa C/efectos de los fármacos , Simportadores/efectos de los fármacos , Animales , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Interneuronas/efectos de los fármacos , Interneuronas/metabolismo , Masculino , Ratas Sprague-Dawley , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/metabolismo , Ácido gamma-Aminobutírico/metabolismo , Ácido gamma-Aminobutírico/farmacología , Cotransportadores de K ClRESUMEN
With Two-photon absorption laser-induced fluorescence(TALIF) technology, leads pulse laser in pure high-enthply flow field from the direction of perpendicular to flow field, and obtains the two-dimension atom O fluorescent signal with ICCD setting outside of test section on the vertical direction of flat made with flow field and laser, this signal reflects the relative concentration of atom O. In paper, given the experimental environment and experimental equipment, to ensure that excitation laser wavelength in experiment is the best one, different angular quantum number on ground state of atom O are tested; finally, it is determined that J=2, wavelength 225.584 nm shall be experimental excitation laser wavelength. To make sure that the obtaining atom O fluorescent signal is in unsaturated linear region, in same condition, changing the excitation laser energy from small to large to test fluorescent signal, ultimately acquiring laser energy linear region is below 3.4 mJ. To record ICCD fluorescent image clearly with optimum contrast, Nikon f=105 mm F/2.8 lens is chosen as experimental lens, and the results are got with an accumulation of 50 times exposure. By analyzing the experimental fluorescent signal, we can get two peak positions on left and right of central line about ±50 mm wide which are generated with compressional wave in supersonic flow field, and atom O concentration has 60 mm wide uniform area in central zone of subsonic flow field, the concentration decreases dramatically. This phenomenon is consistent with flow characteristics of wind tunnel, so the method can be applied to flow parameters measurement in the future.
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BACKGROUND: Hyperalgesia is one of the negative consequences following intraoperative analgesia with remifentanil. Peroxynitrite is a critical determinant in nociceptive process. Peroxynitrite inactivates iron-sulfur cluster that results in mitochondrial dysfunction and the release of iron, leading to mitochondrial iron accumulation. Iron accumulation mediated by divalent metal transporter 1 (DMT1) plays a key role in N-methyl-D-aspartate neurotoxicity. This study aims to determine whether peroxynitrite contributes to remifentanil-induced postoperative hyperalgesia via DMT1-mediated iron accumulation. METHODS: Behavior testing was performed in rat model at different time points. Three-nitrotyrosine, nitrated manganese superoxide dismutase, and DMT1 with/without iron-responsive element [DMT1(+)IRE and DMT1(-)IRE] in spinal cord were detected by Western blot and immunohistochemistry. Spinal iron concentration was measured using the Perl stain and atomic absorption spectrophotometer. Hydrogen-rich saline imparting selectivity for peroxynitrite decomposition and iron chelator was applied in mechanistic study on the roles of peroxynitrite and iron, as well as the prevention of hyperalgesia. RESULTS: Remifentanil induced thermal and mechanical hyperalgesia at postoperative 48 h. Compared with control, there were higher levels of 3-nitrotyrosine (mean ± SD, hyperalgesia vs. control, 1.22 ± 0.18 vs. 0.25 ± 0.05, n = 4), nitrated manganese superoxide dismutase (1.01 ± 0.1 vs. 0.19 ± 0.03, n = 4), DMT1(-)IRE (1.42 ± 0.19 vs. 0.33 ± 0.06, n = 4), and iron concentration (12.87 ± 1.14 vs. 5.26 ± 0.61 µg/g, n = 6) in remifentanil-induced postoperative hyperalgesia, while DMT1(+)IRE was unaffected. Eliminating peroxynitrite with hydrogen-rich saline protected against hyperalgesia and attenuated DMT1(-)IRE overexpression and iron accumulation. Iron chelator prevented hyperalgesia in a dose-dependent manner. CONCLUSIONS: Our study identifies that spinal peroxynitrite activates DMT1(-)IRE, leading to abnormal iron accumulation in remifentanil-induced postoperative hyperalgesia, while providing the rationale for the development of molecular hydrogen and "iron-targeted" therapies.
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Proteínas de Transporte de Catión/biosíntesis , Hiperalgesia/metabolismo , Proteínas Reguladoras del Hierro/biosíntesis , Ácido Peroxinitroso/biosíntesis , Piperidinas/toxicidad , Médula Espinal/metabolismo , Animales , Hiperalgesia/inducido químicamente , Hierro/metabolismo , Masculino , Dolor Postoperatorio/metabolismo , Ratas , Ratas Sprague-Dawley , RemifentaniloRESUMEN
BACKGROUND: Many studies have confirmed that brief remifentanil exposure can enhance pain sensitivity. We previously reported that activation of glycogen synthase kinase-3ß (GSK-3ß) contributes to remifentanil-induced hyperalgesia via regulating N-methyl-D-aspartate receptor plasticity in the spinal dorsal horn. In this study, we demonstrated that GSK-3ß inhibition prevented remifentanil-induced postoperative hyperalgesia via regulating α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) expression and function in the spinal dorsal horn. METHODS: Using a rat model of remifentanil-induced incision hyperalgesia, mechanical and thermal pain was tested 1 day before infusion and 2 hours, 6 hours, 1 day, 2 days, 3 days, 5 days, and 7 days after infusion. Western blot analysis was used to detect AMPAR subunit (GluR1 and GluR2) trafficking, AMPAR phosphorylation status, and GSK-3ß activity in the spinal dorsal horn. Furthermore, whole-cell patch-clamp recording was used to analyze the effect of GSK-3ß inhibition on AMPAR-induced current in the spinal dorsal horn. RESULTS: Membrane AMPAR subunit GluR1 was upregulated in the spinal cord in remifentanil-induced postoperative hyperalgesia rats (275 ± 36.54 [mean ± SD] vs 100 ± 9.53, P = 0.0009). Selective GSK-3ß inhibitors, LiCl and TDZD, treatment ameliorates remifentanil-induced postoperative hyperalgesia, and this was associated with the downregulated GluR1 subunit in the membrane fraction (254 ± 23.51 vs 119 ± 14.74, P = 0.0027; 254 ± 23.51 vs 124 ± 9.35, P = 0.0032). Moreover, remifentanil incubation increased the amplitude and the frequency of AMPAR-induced current in dorsal horn neurons (61.09 ± 9.34 pA vs 32.56 ± 6.44 pA, P = 0.0009; 118.32 ± 20.33 milliseconds vs 643.67 ± 43.29 milliseconds, P = 0.0002), which was prevented with the application of LiCl and TDZD, respectively. Remifentanil-induced postoperative pain induced an increase in pGluR1 Ser845 and Rab5, which was prevented with the application of LiCl and TDZD. CONCLUSIONS: These results indicate that amelioration of remifentanil-induced postoperative hyperalgesia by GSK-3ß inhibition is attributed to downregulated AMPAR GluR1 expression in the membrane fraction and inhibition of AMPAR function via altering pGluR1 and Rab5 expression in the spinal dorsal horn.
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Regulación de la Expresión Génica , Glucógeno Sintasa Quinasa 3/metabolismo , Hiperalgesia/metabolismo , Dolor Postoperatorio/metabolismo , Piperidinas/efectos adversos , Receptores AMPA/biosíntesis , Animales , Inhibidores Enzimáticos/farmacología , Glucógeno Sintasa Quinasa 3/antagonistas & inhibidores , Glucógeno Sintasa Quinasa 3 beta , Hiperalgesia/inducido químicamente , Hiperalgesia/prevención & control , Masculino , Técnicas de Cultivo de Órganos , Dolor Postoperatorio/inducido químicamente , Dolor Postoperatorio/prevención & control , Piperidinas/antagonistas & inhibidores , Células del Asta Posterior/efectos de los fármacos , Células del Asta Posterior/metabolismo , Ratas , Ratas Sprague-Dawley , Receptores AMPA/antagonistas & inhibidores , RemifentaniloRESUMEN
This paper introduces the experiment technology for measuring the radiation of high temperature gas in the high frequency plasma wind tunnel. The infrared radiation of carbon dioxide at high temperature has been measured using this technology. We introduced the principium, flow field and the working gas of the high frequency plasma wind tunnel. The experiment condition, equipment, method of data processing and the analyse of the experiment results were introduced. We had measured the infrared radiation of carbon dioxide at four different temperatures between 1500 and 3000 K using this technology for measuring the radiation of high temperature gas which had been developed by ourselves. Measuring the spatial distribution of the infrared radiation of carbon dioxide using Able-transform were also introduced. We have analyzed the emission spectrum at 4.3 µm of carbon dioxide at high temperature. The conclusion had been obtained that the center wavelength of the emission spectrum moved to the long wave when the temperature risen. The authors also had analyzed and contrasted the experiment results and the data obtained from literatures.
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A great number of COVID-19 patients was caused by Omicron BA.5 subvariant between December 2022 and January 2023 after the end of the zero-COVID-19 policy in China. In this study, we clarified the epidemiological and immunological characteristics of 457 enrolled middle-aged and elderly population in two housing estates after Omicron BA.5 wave. A total of 89.9 % (411/457) individuals have suffered Omicron BA.5 infection, among which 78.1 % (321/411) were symptomatic. The elderly patients were more likely to show fatigue and had longer symptomatic period than that of middle-aged patients post Omicron BA.5 infection. Omicron XBB and BA.2.86 subvariants extensively escaped the immunity elicited by Omicron BA.5 infection. The level of neutralizing antibody was mostly affected by vaccination doses rather than underlying disease status in these participants. It is very important to strengthen the epidemiological investigation and immune resistance assessment among elderly population for control of emerging SARS-CoV-2 variants.
RESUMEN
Introduction: With the continued prevalence of COVID-19, repeated infection caused by SARS-CoV-2 has become common. However, studies on immune persistence post Omicron XBB reinfection are limited. Methods: We prospectively studied the durability and cross-reactivity of neutralizing antibodies (NAbs) and T cell responses among 20 subjects who suffered Omicron BA.5 infection with or without Omicron XBB reinfection over 6-month through the pseudovirus neutralization test and the fluorospot assay. Results: NAbs against EG.5.1, BA.2.86, and JN.1 subvariants were decreased and undetectable at 6-month post Omicron BA.5 infection, while those elicited by Omicron XBB reinfection were significant increased and remained detectable against all detected variants within 6-month. Furthermore, in subjects with Omicron XBB reinfection, memory T cell responses could cross-recognized wild-type and Omicron spike peptides and reached peak at 3-month. Interestingly, comparable robust T cell responses were observed among non-seroconverted subjects post Omicron XBB exposure. Conclusion: Though the NAbs against various emerging Omicron subvariants elicited by Omicron XBB reinfection can persist for at least 6-month, the HCWs should strengthen personal protection and timely be immunized with updated vaccines upon current circulating variants or conserved T epitope.