RESUMO
The eradication of tuberculosis remains a global challenge. Despite being the only licensed vaccine, Bacillus Calmette-Guérin (BCG) confers limited protective efficacy in adults and individuals with latent tuberculosis infections (LTBI). There is an urgent need to develop novel vaccines that can enhance the protective effect of BCG. Protein subunit vaccines have garnered significant research interest due to their safety and plasticity. Based on previous studies, we selected three antigens associated with LTBI (Rv2028c, Rv2029c, Rv3126c) and fused them with an immunodominant antigen Ag85A, resulting in the construction of a multistage protein subunit vaccine named A986. We evaluated the protective effect of recombinant protein A986 adjuvanted with MPL/QS21 as a booster vaccine for BCG against Mycobacterium tuberculosis (Mtb) infection in mice. The A986 + MPL/QS21 induced the secretion of antigen-specific Th1 (IL-2+, IFN-γ+ and TNF-α+) and Th17 (IL-17A+) cytokines in CD4+ and CD8+ T cells within the lung and spleen of mice, while also increased the frequency of central memory and effector memory T cells. Additionally, it also induced the enhanced production of IgG antibodies. Compared to BCG alone, A986 + MPL/QS21 boosting significantly augmented the proliferation of antigen-specific multifunctional T cells and effectively reduced bacterial load in infected mice. Taken together, A986 + MPL/QS21 formulation induced robust antigen-specific immune responses and provided enhanced protection against Mtb infection as a booster of BCG vaccine.
Assuntos
Antígenos de Bactérias , Vacina BCG , Citocinas , Mycobacterium tuberculosis , Tuberculose , Vacinas de Subunidades Antigênicas , Animais , Vacinas de Subunidades Antigênicas/imunologia , Mycobacterium tuberculosis/imunologia , Vacina BCG/imunologia , Antígenos de Bactérias/imunologia , Feminino , Tuberculose/prevenção & controle , Tuberculose/imunologia , Camundongos , Citocinas/metabolismo , Imunização Secundária , Modelos Animais de Doenças , Adjuvantes Imunológicos/administração & dosagem , Vacinas contra a Tuberculose/imunologia , Vacinas contra a Tuberculose/administração & dosagem , Anticorpos Antibacterianos/sangue , Anticorpos Antibacterianos/imunologia , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos BALB C , Aciltransferases/imunologia , Pulmão/imunologia , Pulmão/microbiologia , Pulmão/patologia , Proteínas de Bactérias/imunologia , HumanosRESUMO
One-quarter of the world's population is infected with Mycobacterium tuberculosis (Mtb). After initial exposure, more immune-competent persons develop asymptomatic latent tuberculosis infection (LTBI) but not active diseases, creates an extensive reservoir at risk of developing active tuberculosis. Previously, we constructed a novel recombinant Sendai virus (SeV)-vectored vaccine encoding two dominant antigens of Mtb, which elicited immune protection against acute Mtb infection. In this study, nine Mtb latency-associated antigens were screened as potential supplementary vaccine candidate antigens, and three antigens (Rv2029c, Rv2028c, and Rv3126c) were selected based on their immune-therapeutic effect in mice, and their elevated immune responses in LTBI human populations. Then, a recombinant SeV-vectored vaccine, termed SeV986A, that expresses three latency-associated antigens and Ag85A was constructed. In murine models, the doses, titers, and inoculation sites of SeV986A were optimized, and its immunogenicity in BCG-primed and BCG-naive mice were determined. Enhanced immune protection against the Mtb challenge was shown in both acute-infection and latent-infection murine models. The expression levels of several T-cell exhaustion markers were significantly lower in the SeV986A-vaccinated group, suggesting that the expression of latency-associated antigens inhibited the T-cell exhaustion process in LTBI infection. Hence, the multistage quarter-antigenic SeV986A vaccine holds considerable promise as a novel post-exposure prophylaxis vaccine against tuberculosis.
Assuntos
Tuberculose Latente , Mycobacterium tuberculosis , Tuberculose , Humanos , Animais , Camundongos , Tuberculose Latente/prevenção & controle , Vírus Sendai/genética , Vacina BCG , Antígenos de Bactérias/genética , Tuberculose/microbiologia , Mycobacterium tuberculosis/genética , Vacinas Sintéticas/genéticaRESUMO
Trained immunity is one of the mechanisms by which BCG vaccination confers persistent nonspecific protection against diverse diseases. Genomic differences between the different BCG vaccine strains that are in global use could result in variable protection against tuberculosis and therapeutic effects on bladder cancer. In this study, we found that four representative BCG strains (BCG-Russia, BCG-Sweden, BCG-China, and BCG-Pasteur) covering all four genetic clusters differed in their ability to induce trained immunity and nonspecific protection. The trained immunity induced by BCG was associated with the Akt-mTOR-HIF1α axis, glycolysis, and NOD-like receptor signaling pathway. Multi-omics analysis (epigenomics, transcriptomics, and metabolomics) showed that linoleic acid metabolism was correlated with the trained immunity-inducing capacity of different BCG strains. Linoleic acid participated in the induction of trained immunity and could act as adjuvants to enhance BCG-induced trained immunity, revealing a trained immunity-inducing signaling pathway that could be used in the adjuvant development.
Assuntos
Vacina BCG , Tuberculose , Humanos , Ácido Linoleico , Imunidade Treinada , Multiômica , Adjuvantes Imunológicos/farmacologiaRESUMO
Interactions of vascular endothelial growth factor (VEGF) with receptors VEGFR1/Flt1 and VEGFR2/Flk1, and those of angiopoietins (Ang-1, Ang-2) with receptor Tie2 play important roles in placental angiogenesis. This study investigated vascular morphology and expression of these angiogenic factors in rat placenta on the day 15, 18, 21 of gestation (D15, D18 and D21). The rats were randomly assigned into 3 groups: normal group, model group [fetal growth restriction (FGR) model], and Bushen Yiqi Huoxue (BYHR) recipe treatment group (BYHR group, the pregnant rats with FGR were treated with BYHR recipe). Morphological analysis indicated that during initial villous formation, fetal nucleated erythrocytes (FNEs) appeared in maternal blood sinus (MBS). Subsequently, FNEs were surrounded by endothelial cells to form fetal capillary (FC) and then by trophoblast cells to form villi. As pregnancy proceeded, FC density increased progressively with increasing endothelial identification staining (EIS) in normal and BYHR groups. Whereas, villous formation was suppressed, normal increase in FC density was impaired and EIS was weakened in model group. Quantitative PCR analysis showed that VEGF and Flk1 mRNA increased over gestation in all groups, indicating that VEGF might play a pivotal role in FC growth during late gestation. VEGF mRNA was increased on D15, while decreased on D21 in model group as compared with normal group and BYHR group. Immunohistochemically, Ang-2 protein was highly expressed in FNEs, gradually disappeared as villi matured, and decreased over gestation in all groups, indicating that Ang-2 might play a pivotal role in villous formation, which was further supported by decreased Ang-2 mRNA and protein expression in model group on D15. Ang-1 mRNA, Tie2 mRNA and Ang-1/Ang-2 ratio increased from D15 to D18 in all groups as placenta matured. Ang-1 mRNA, Tie2 mRNA and Ang-1/Ang-2 ratio were decreased on D18 in model group as compared with normal and BYHR groups, indicating delayed maturity of FGR placenta. Alterations in angiogenic factors may result in altered placental vasculature and cause placental insufficiency. BYHR recipe could balance the angiogenic factors to promote the formation and maturation of FGR placental vasculature.
Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Retardo do Crescimento Fetal/etiologia , Retardo do Crescimento Fetal/fisiopatologia , Neovascularização Fisiológica/fisiologia , Placenta/irrigação sanguínea , Placenta/fisiopatologia , Poluição por Fumaça de Tabaco/efeitos adversos , Animais , Feminino , Retardo do Crescimento Fetal/terapia , Masculino , Neovascularização Fisiológica/efeitos dos fármacos , Placenta/efeitos dos fármacos , Gravidez , Ratos , Ratos Sprague-DawleyRESUMO
Despite the great promise initially demonstrated by photothermal ablation (PTA) therapy, its inability to completely ablate large tumors is problematic, because this has been found to result in residual tumors at ablation margins and bring a relative high rate of subsequent recurrences and metastases. To address this issue, we herein report a smart photothermal nanosystem (PBM) based on FDA-approved Prussian blue (PB) nanoparticles, doped with Mn (III) to suppress the tumor debris left by incomplete ablation. Notably, our study demonstrated that PTA-induced hyperthermia plays a crucial role in initiating the cGAS-STING pathway by generating damaged cytosolic DNA. This PBM nanosystem, which consumes glutathione and continuously releases Mn(II), further amplifies the PTA-induced cGAS-STING pathway in CT26 colon and 4T1 breast tumor models. Moreover, treatment with PBM following PTA boosted the robust immune response in situ and extended to the whole body with a remarkable suppression effect on both local residual and distant tumors. This work, which improves the antitumor efficacy of nonablated areas utilizing hyperthermia-enhanced immune therapy, may therefore provide a promising adjuvant antitumor strategy for the issue of incomplete ablation. STATEMENT OF SIGNIFICANCE: This work discovered, for the first time, that photothermal ablation-induced hyperthermia plays a crucial role in initiating the cGAS-STING pathway. Taking advantage of this finding, we developed a smart photothermal material (PBM) tailored for incomplete tumor ablation. This integrated Mn(III)-doped nanosystem (PBM) demonstrated superior therapeutic benefits due to the thermal ablation process and immune enhancement. As the photothermal ablation-induced cGAS-STING pathway was triggered, the released Mn(III) consumes GSH while continuously transferred to Mn(II), which further amplified STING activation and facilitated a more robust antitumor immunity, thereby remarkably inhibiting both local residual and distant tumors in virtue of the biological changes under thermal ablation.
Assuntos
Hipertermia Induzida , Nanopartículas , Neoplasias , Humanos , Manganês/farmacologia , Neoplasias/terapia , Nucleotidiltransferases/genética , Nucleotidiltransferases/metabolismoRESUMO
BACKGROUND: Recombinant protein subunit vaccination is considered to be a safe, fast and reliable technique when combating emerging and re-emerging diseases such as coronavirus disease 2019 (COVID-19). Typically, such subunit vaccines require the addition of adjuvants to attain adequate immunogenicity. AS01, which contains adjuvants MPL and saponin QS21, is a liposome-based vaccine adjuvant system that is one of the leading candidates. However, the adjuvant effect of AS01 in COVID-19 vaccines is not well described yet. METHODS: In this study, we utilized a mixture of AS01 as the adjuvant for an S1 protein-based COVID-19 vaccine. RESULTS: The adjuvanted vaccine induced robust immunoglobulin G (IgG) binding antibody and virus-neutralizing antibody responses. Importantly, two doses induced similar levels of IgG binding antibody and neutralizing antibody responses compared with three doses and the antibody responses weakened only slightly over time up to six weeks after immunization. CONCLUSION: These results suggested that two doses may be enough for a clinical vaccine strategy design using MPL & QS21 adjuvanted recombinant protein, especially in consideration of the limited production capacity of COVID-19 vaccine in a public health emergency.
Assuntos
Antígenos Virais/imunologia , Vacinas contra COVID-19/imunologia , COVID-19/imunologia , Lipídeo A/análogos & derivados , SARS-CoV-2/imunologia , Saponinas/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Vacinas de Subunidades Antigênicas/imunologia , Adjuvantes Imunológicos/administração & dosagem , Adjuvantes de Vacinas/administração & dosagem , Animais , Anticorpos Neutralizantes , Anticorpos Antivirais/metabolismo , Formação de Anticorpos , COVID-19/virologia , Relação Dose-Resposta Imunológica , Combinação de Medicamentos , Feminino , Células HEK293 , Humanos , Imunização , Imunogenicidade da Vacina , Lipídeo A/administração & dosagem , Lipídeo A/imunologia , Camundongos Endogâmicos BALB C , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/imunologia , Saponinas/administração & dosagemRESUMO
Trichomes, which develop from epidermal cells, are considered one of the important characteristics of the tea plant [Camellia sinensis (L.) O. Kuntze]. Many nutritional and metabolomic studies have indicated the important contributions of trichomes to tea products quality. However, understanding the regulation of trichome formation at the molecular level remains elusive in tea plants. Herein, we present a genome-wide comparative transcriptome analysis between the hairless Chuyeqi (CYQ) with fewer trichomes and the hairy Budiaomao (BDM) with more trichomes tea plant genotypes, toward the identification of biological processes and functional gene activities that occur during trichome development. In the present study, trichomes in both cultivars CYQ and BDM were unicellular, unbranched, straight, and soft-structured. The density of trichomes was the highest in the bud and tender leaf periods. Further, using the high-throughput sequencing method, we identified 48,856 unigenes, of which 31,574 were differentially expressed. In an analysis of 208 differentially expressed genes (DEGs) encoding transcription factors (TFs), five may involve in trichome development. In addition, on the basis of the Gene Ontology (GO) annotation and the weighted gene co-expression network analysis (WGCNA) results, we screened several DEGs that may contribute to trichome growth, including 66 DEGs related to plant resistance genes (PRGs), 172 DEGs related to cell wall biosynthesis pathway, 29 DEGs related to cell cycle pathway, and 45 DEGs related to cytoskeleton biosynthesis. Collectively, this study provided high-quality RNA-seq information to improve our understanding of the molecular regulatory mechanism of trichome development and lay a foundation for additional trichome studies in tea plants.
RESUMO
OBJECTIVE: To study the diagnostic value of heart rate variability (HRV) in heart dysfunction in children with beta-thalassemia major (ß-TM)by examining the changes of HRV in ß-TM children. METHODS: A 24 hours Holter monitoring electrocardiogram (Holter) was performed in 21 children with ß-TM and 15 healthy children (control group). The time domain and frequency domain indexes of HRV in the two groups were compared. The correlation between serum ferritin levels and HRV was evaluated. RESULTS: The time domain indexes SDNN, rMSSD and PNN50 and the frequency domain indexes very low frequency (VLF), low frequency (LF) and high frequency (HF) in the ß-TM group were significantly lower than in the control group (P<0.05). There was no correlation between serum ferritin level and HRV in children with ß-TM. CONCLUSIONS: The autonomic nerve dysfunction exists in children with ß-TM. HRV analysis is useful in the prediction of early cardiac dysfunction in children with ß-TM.
Assuntos
Frequência Cardíaca/fisiologia , Talassemia beta/fisiopatologia , Adolescente , Criança , Feminino , Ferritinas/sangue , Humanos , Masculino , Talassemia beta/sangueRESUMO
Biochar has been applied widely as an amendment in the remediation of contaminated soil to immobilize the heavy metals. However, the role of ultraviolet (UV) irradiation modified biochar derived from the residues of phytoremediation plants in the contaminated soil not investigated yet. In this study, the UV-modified biochars were obtained from Brassica napus L. and Lolium perenne L. by pyrolysis at 600 °C. They were applied in a pot experiment to investigate their effect on Cd bioavailability and uptake in Coriandrum sativum L. in a Cd-contaminated soil at four addition rate (0%, 0.2%, 0.4%, and 0.6%). The results showed that the Cd was effectively stabilized in the biochar with environmentally acceptable leaching toxicity. The specific surface area and carboxyl functional group of biochar were greatly increased after UV modification. The application of biochar progressively increased the soil pH and electrical conductivity (EC). Furthermore, the CaCl2-extractable Cd was significantly reduced by 18.4-51.4% with biochar amendments. The concentration of Cd in shoots and roots was significantly reduced by biochars. In conclusion, the UV-modified biochar obtained from phytoremediation residue could effectively deal with hazardous waste and repair Cd-contaminated soil.
Assuntos
Coriandrum , Poluentes do Solo , Biodegradação Ambiental , Disponibilidade Biológica , Cádmio/análise , Carvão Vegetal , Solo , Poluentes do Solo/análiseRESUMO
Reducing the content of Cd in wheat grains is necessary for human health, especially in alkaline farmland in northern China where a large area of soils is heavily polluted with Cd. A field experiment was conducted to investigate the effects of wheat straw biochar (WB) and maize straw biochar (MB) combined solely with ferrous sulfate (FeSO4) or combined with FeSO4 and pig manure (PFWB and PFMB) on Cd bioavailability in soil and the phytotoxicity of Cd in wheat in an alkaline contaminated soil. The results showed that the application of these treatments decreased the concentrations of CaCl2-extractable Cd by 32.8-60.5% and increased the soil organic matter by 36.8-106.7% compared with those of the control treatment. The acid-soluble fraction of Cd was decreased by 3.7-16.8% but the residual fraction was increased by 1.7-13.7%. Furthermore, the addition of WB and MB increased the soil pH by 0.29 and 0.16 units, respectively, while the other treatments decreased the soil pH by 0.16-0.37 units. The concentrations of Cd in different wheat tissues were decreased in amended soils, and these decreases were positively correlated with CaCl2-extractable Cd and the acid-soluble fraction of Cd. The ability to accumulate Cd was in the order of root>straw>grain. In addition, there was a downward trend in the bio-concentration and translocation factors under different amendments. The amendments of PFWB and PFMB had better efficiency in the immobilization of Cd in soil and the inhibition of Cd uptake of wheat than WB and MB. In addition, the treatments of PFWB and PFMB increased the wheat yield by 14.3-16.2%, and thus have a great application prospect based on the cost-benefit analysis.
Assuntos
Oryza , Poluentes do Solo , Animais , Disponibilidade Biológica , Cádmio/análise , Cádmio/toxicidade , Carvão Vegetal , China , Compostos Ferrosos , Esterco , Solo , Poluentes do Solo/análise , Poluentes do Solo/toxicidade , Suínos , TriticumRESUMO
Saccharomyces boulardii (S. boulardii) is a probiotic yeast that is widely used to treat gastrointestinal disorders. The present study is aimed to explore the therapeutic effects of S. boulardii on dextran sulfate sodium- (DSS-) induced murine ulcerative colitis (UC) and illustrate the mechanisms of action. C57BL/6 mice were administered S. boulardii (105 and 107 CFU/ml, p.o.) for 3 weeks and then given DSS [2.5% (w/v)] for one week. Administration of S. boulardii prevented DSS-induced reduction in body weight, diarrhea, bloody feces, decreased colon length, and loss of histological structure. Moreover, S. boulardii protected the intestinal barrier by increasing the levels of tight junction proteins zona occludens-1 and Occludin and exerted immunomodulatory effects in DSS-induced mice. Furthermore, S. boulardii suppressed the colonic inflammation by reducing the levels of Interleukin-1ß, Interleukin-6, and Tumor necrosis factor alpha and restored myeloperoxidase activity in mice exposed to DSS. S. boulardii also mitigated colonic oxidative damage by increasing the levels of antioxidant enzymes (superoxide dismutase, catalase, and heme oxygenase 1) and glutathione and decreasing malondialdehyde accumulation. Further studies identified that S. boulardii suppressed the nuclear translocation of nuclear factor kappa B (NF-κB) p65 subunit by decreasing IκKα/ß levels, while promoted the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) in DSS-exposed mice. Collectively, S. boulardii possessed an appreciable therapeutic effect against the experimental mice model of UC. The protective mechanism of S. boulardii may involve inhibition of NF-κB-mediated proinflammatory signaling and activation of Nrf2-modulated antioxidant defense in addition to intestinal barrier protective and immunomodulatory effects.
Assuntos
Colite Ulcerativa/prevenção & controle , Sulfato de Dextrana/toxicidade , Regulação da Expressão Gênica , Inflamação/prevenção & controle , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Saccharomyces boulardii/fisiologia , Animais , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/metabolismo , Colite Ulcerativa/patologia , Feminino , Inflamação/induzido quimicamente , Inflamação/metabolismo , Inflamação/patologia , Camundongos , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2/genética , NF-kappa B/genética , Saccharomyces boulardii/química , Transdução de SinaisRESUMO
Tumor antigens (Ags) are weakly immunogenic and elicit inadequate immune responses, thus induction of antigen-specific immune activation via the maturation of dendritic cells (DCs) is a strategy used for cancer immunotherapy. In this study, we examined the effect of Rv3628 from Mycobacterium tuberculosis (Mtb) on activation of DCs and anti-tumor immunity in vivo. Intravenous injection of mice with Rv3628 promoted DC activation of spleen and lymph nodes. More importantly, Rv3628 also induced activation of DCs and enhanced Ag presentation in tumor-bearing mice. In mice bearing ovalbumin (OVA)-expressing tumors, combination treatment with Rv3628 and OVA peptide promoted OVA-specific T cell activation and accumulation of interferon (IFN)-γ and tumor necrosis factor (TNF)-α-producing OT-I and OT-II cells in tumor-draining lymph nodes. Moreover, three different tumor Ags in three different tumor models showed enhanced anti-tumor activity with Rv3628 as adjuvant, including inhibition of growth of OVA-expressing B16 melanoma, CT26 carcinoma, and B16 melanoma tumors, and a synergistic effect with anti-programmed cell death protein 1 (PD-1) antibody treatment. Additionally, potential application against human tumors was indicated by similar activation of human peripheral blood DCs by Rv3628. Taken together, these data demonstrate that Rv3628 could be an effective adjuvant in tumor immunotherapy via enhanced capacity of DC activation and Ag presentation.
RESUMO
OBJECTIVE: To observe the effect of Bushen Yiqi Huoxue Recipe (BYHR, a Chinese medical prescription for reinforcing Shen, replenishing qi and promoting blood circulation) on placental trophoblast apoptosis in fetal growth restricted (FGR) pregnant rat for the sake of explore its mechanism of action in treating FGR. METHODS: FGR animal model was established by passive smoking, 32 pregnant rats were divided into four groups at random: the normal group, the model group, the Chinese medicine (CM) group (model rats treated by BYHR) and the Western medicine (WM) group (model rats treated by arginine). The histological change of placenta was examined with HE stain, the trophoblast apoptosis was detected by TUNEL and RT-PCR, and the expressions of Bcl-2 and Bax in the placenta were detected by immunohistochemical method. RESULTS: Blood stasis and villous ischemia were seen in placenta of FGR model rats. Placental microcirculation was significantly improved in the CM group, but in the WM group only partially improved. The median apoptotic index of syncytial trophoblast cells in the four groups, in normal, model, CM, and WM order, was 45%, 75%, 57% and 70%, as compared with the model group, it was much lower in the normal group and the CM group (P < 0.01), but a similar level was shown in the WM group. No significant difference in mRNA and protein expressions of Bcl-2 and Bax was found among the four groups. CONCLUSION: BYHR can improve the placental microcirculation in FGR rats to prevent excessive apoptosis through a mechanism other than the classical Bax/Bcl-2 apoptotic pathway, which needs further exploring.
Assuntos
Apoptose/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Retardo do Crescimento Fetal/prevenção & controle , Placenta/citologia , Trofoblastos/citologia , Animais , Feminino , Microcirculação/efeitos dos fármacos , Placenta/irrigação sanguínea , Gravidez , RatosRESUMO
The perturbed genes from transcriptomes are often presented in terms of relative expressions against control samples. However, the probe signal values (PSVs) of genes, implying protein abundances, are often ignored. Here, we explored the PSVs in tuberculosis (TB)-relevant signature genes. The signatures from Mycobacterium tuberculosis-infected THP-1 cells were defined as induced (TMtb-i, with a derived TMtb-iNet) and repressed (TMtb-r). The signature from human blood was defined as a pulmonary TB (PTB)-specific signature (PTBsig). The analysis showed that before infection, TMtb-i and TMtb-iNet had lower PSVs and TMtb-r genes had average PSVs. In the blood of healthy donors, PTBsig (divided into up-regulated PTBsigUp and down-regulated PTBsigDn) displayed average PSVs. This was partly due to masking by the cellular heterogeneity of blood; diverse PSVs were seen in constituent cell populations (CD4/8+ T, monocytes and neutrophils). Specifically, the PSVs of PTBsigUp in the neutrophils of healthy donors were higher (implying higher protein abundances), and much higher in the neutrophils of PTB (implying excessive protein abundances). Based on the PSV patterns of PTBsigUp in four cell populations, we identified three representative highly homologous genes (FCGR1A, FCGR1B, and the pseudogene FCGR1CP, which were often poorly distinguished), of which the summed PSVs were the highest in the neutrophils of PTB patients and healthy donors. The three genes were all up-regulated and responsive to chemotherapy in the blood of PTB, as validated in an RNA-seq-based analysis. This PSV-based study confirms the excessive involvement of neutrophil FCGR1 in PTB.
RESUMO
Various phytoremediation residues (PMRs), including Brassica napus L. (BN), Pennisetum sinese (PS) and Lolium perenne L.(LP), were pyrolyzed at 400, 500, 600 and 700 °C, respectively. A series of sequential and single extractions were employed to analyze the chemical speciation and potential environmental risk of Cadmium (Cd) in different phytoremediation residues-derived biochars (PMBs). The results showed that the exchangeable Cd fraction decreased but the residual Cd fraction increased, indicating the inhibition of bioavailability of Cd and low potential ecological risk index of PMBs. When the temperature was over 600 °C, the Cd in biochar was acceptable to the environment and the leaching concentration of Cd extracted by the three extraction methods (distilled water, SPLP and TCLP) were all under the standard limit. Findings from this study illustrated that the treatment of pyrolysis was feasible for the three kinds of PMRs at 600 °C with acceptable environment risk.
Assuntos
Cádmio , Pirólise , Biodegradação Ambiental , Carvão VegetalRESUMO
BACKGROUND: CD69 is a biomarker of T-cell activation status, but its activation status in human Mycobacterium tuberculosis (Mtb) infection remains elusive. METHODS: A set of cohorts of patients with different tuberculosis (TB) infection status including active TB patients (ATB), latent tuberculous infection patients (LTBI) and close contacts (CCs) of ATB was designed, and the expression profiles of CD69 and several T-cell markers were determined on Mtb antigen-stimulated T cells by flow cytometry. RESULTS: The frequencies of CD4+ and CD8+ T cells were both comparable among Mtb-infected individuals including ATB and LTBI, which guaranteed the consistency of the background level. A t-Distributed Stochastic Neighbor Embedding (tSNE) analysis on a panel of six phenotypic markers showed a unique color map axis gated on T cells in the CCs group compared with ATB and LTBI populations. By further gating on cells positive for each individual marker and then overlaying those events on top of the tSNE plots, their distribution suggested that some markers were expressed differently in the CCs group. Further analysis showed that the expression levels of CD69 on both CD4+ and CD8+ T cells were significantly lower in the CCs group, especially in interferon-γ-responding T cells. CONCLUSION: Our findings suggest that the T-cell activation status of CD69 is associated with Mtb infection and may have the potential to distinguish LTBI from those populations who have been exposed continuously to Mtb but have not become infected.
Assuntos
Infecções por HIV , Mycobacterium tuberculosis , Tuberculose Pulmonar , Tuberculose , Adulto , Humanos , Sistemas Automatizados de Assistência Junto ao Leito , Tuberculose/diagnóstico , Tuberculose Pulmonar/diagnóstico , Lipopolissacarídeos , Infecções por HIV/diagnóstico , Sensibilidade e Especificidade , EscarroRESUMO
Smoking increases the risk of pregnancy complications such as spontaneous abortion and low birth weight (LBW). By cigarette smoke exposure (gestational day, GD3-17), normal-litter-size pregnancy with low birth weight (NP-LBW) and small-litter-size pregnancy with normal birth weight (SP-NBW) in rats were induced. The placental weight in SP-NBW was twice the weight of the normal in contrast with the smaller placenta in NP-LBW. Compared with the normal, placental efficiency (expressed as fetus-to-placenta weight ratio) and placental vascularisation were significantly decreased in smoke exposed placentas with more obvious decrease in SP-NBW. For NP-LBW, decreased placental vascularisation was due to decreased labyrinth vascularisation which was caused by both decreased number density and diameter of fetal capillary. For SP-NBW, decreased placental vascularisation was due to reduced proportion of labyrinth in placenta and decreased labyrinth vascularisation which was caused by decreased fetal capillary number density. Real time RT-PCR analysis showed a tendency for decreased placental mRNA level of vascular endothelial growth factor (VEGF), angiopoietin-1 (Ang1) and tyrosine kinase receptor-2 (Tie2) in NP-LBW(P<0.1), and the tendency became obvious in SP-NBW(P<0.05). A tendency for decreased placental mRNA level of fms-like tyrosine kinase-1(Flt1) and angiopoietin-2 (Ang2) was also observed in SP-LBW(P<0.1). Our data demonstrated the synergistic negative effect of gestational smoke-exposure and small litter size on placental efficiency, placental vascularisation and placental angiogenic growth factor mRNA expression in rat.
Assuntos
Regulação da Expressão Gênica/efeitos dos fármacos , Tamanho da Ninhada de Vivíparos , Neovascularização Fisiológica/efeitos dos fármacos , Placenta/efeitos dos fármacos , Placenta/fisiologia , Fumaça/efeitos adversos , Animais , Peso ao Nascer/efeitos dos fármacos , Feminino , Tamanho do Órgão/efeitos dos fármacos , Placenta/irrigação sanguínea , Placenta/metabolismo , Gravidez , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RatosRESUMO
OBJECTIVE: Visceral adipose tissue (VAT) and hepatic fat deposition are the most important risk factors for women's health. Acupuncture, including electroacupuncture (EA), is used to treat obesity throughout the world. The effect of EA is evaluated mainly by body mass index (BMI) and waist circumference (WC). Few studies have assessed its effect in reducing VAT volume and hepatic fat fraction (HFF) based on an exact measurement method such as magnetic resonance imaging (MRI). This study aimed to resolve this issue. METHODS: Thirty subjects were randomly divided into two groups. The control group (n = 15) did not receive any intervention and maintained a normal diet and their usual exercise habits. The treatment group (n = 15) received EA three times a week for 3 months. BMI and WC were measured using different devices. VAT and HFF were measured by MRI and calculated by related software before and after the intervention. RESULTS: A marked difference was evident in group that received EA treatment in the following tests. The differences in BMI (U = 21.00, p < 0.001), WC (U = 40.50, p = 0.002), VAT volume (U = 13.00, p < 0.001), and mean HFF (U = 0.00, p < 0.001) before and after the intervention in the treatment group were distinct and significant compared with those of the control group. Three months later, the treatment group showed a lower BMI (W = 91.00, p = 0.001), WC (t = 4.755, p < 0.001), VAT volume (t = 5.164, p < 0.001), and mean HFF (W = 120.00, p = 0.001) compared with pretreatment levels. Compared with the control group, the treatment group showed a lower VAT volume (t = 60.00, p = 0.029) after 3 months of treatment. After 3 months, the control group showed higher mean HFF (t = -2.900, p = 0.012) and VAT volume (W = 11.50, p = 0.006) compared with their initial levels. CONCLUSION: Based on MRI evaluation, this randomized controlled study proved that EA treatment reduces BMI and WC as well as VAT volume and HFF in women with abdominal obesity.