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1.
Clin Exp Immunol ; 2022 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-35551362

RESUMO

Cytomegalovirus (CMV) infection and acute graft-versus-host disease (aGVHD) are two major complications that contribute to a poor prognosis after hematopoietic stem cell transplantation (HSCT). Superior early immune reconstitution (IR) is associated with improved survival after HSCT. However, when all three factors, CMV infection, aGVHD, and IR, are concomitantly considered, the effects of the triple events on HSCT are still unknown and should be studied further. Thus we enrolled 185 patients who were diagnosed as hematological malignancies and treated with HLA-matched sibling transplantation (MST) between January 2010 and December 2014, of whom 83 were positive for CMV infection and 82 had aGVHD. Results showed that patients with both aGVHD and CMV infection had significantly higher non-relapse mortality (NRM), lower overall survival (OS), and delayed CD8+ T-cell IR. Multivariate analyses showed that both aGVHD combined with CMV infection and delayed CD8+ T-cell IR were independent risk factors for post-MST prognosis. Recurrent CMV infections are associated with poor CD8+ T-cell reconstitution. However, superior IR could protect against the negative effects of aGVHD and CMV infection on the transplant outcomes.

2.
Front Cell Infect Microbiol ; 12: 833080, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35573776

RESUMO

Hypervirulent Klebsiella pneumoniae (hvKp) can cause life-threatening community-acquired infections among healthy young individuals and is thus of concern for global dissemination. In this study, a mouse model of acute primary hvKp pneumonia was established via aerosolized intratracheal (i.t.) inoculation, laying the foundation for conducting extensive studies related to hvKp. Subsequently, a time-course transcriptional profile was created of the lungs from the mouse model at 0, 12, 24, 48 and 60 hours post-infection (hpi) using RNA Sequencing (RNA-Seq). RNA-Seq data were analyzed with the use of Mfuzz time clustering, weighted gene co-expression network analysis (WGCNA) and Immune Cell Abundance Identifier for mouse (ImmuCellAI-mouse). A gradual change in the transcriptional profile of the lungs was observed that reflected expected disease progression. At 12 hpi, genes related to acute phase inflammatory response increased in expression and lipid metabolism appeared to have a pro-inflammatory effect. At 24 hpi, exacerbation of inflammation was observed and active IFN-γ suggested that signaling promoted activation and recruitment of macrophages occurred. Genes related to maintaining the structural integrity of lung tissues showed a sustained decrease in expression after infection and the decrease was especially marked at 48 hpi. TNF, IL-17, MAPK and NF-kB signaling pathways may play key roles in the immunopathogenesis mechanism at all stages of infection. Natural killer (NK) cells consistently decreased in abundance after infection, which has rarely been reported in hvKp infection and could provide a new target for treatment. Genes Saa1 and Slpi were significantly upregulated during infection. Both Saa1, which is associated with lipopolysaccharide (LPS) that elicits host inflammatory response, and Slpi, which encodes an antimicrobial protein, have not previously been reported in hvKp infections and could be important targets for subsequent studies. To t our knowledge, this paper represents the first study to investigate the pulmonary transcriptional response to hvKp infection. The results provide new insights into the molecular mechanisms underlying the pathogenesis of hvKp pulmonary infection that can contribute to the development of therapies to reduce hvKp pneumonia.

3.
Spectrochim Acta A Mol Biomol Spectrosc ; 277: 121260, 2022 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-35447557

RESUMO

We developed a dual-wavelength-excitation aerosol fluorescence spectra detection device prototype. In our system, the 263 nm and 355 nm lasers are used to sequentially excite the fluorescence of aerosol stream, which is located spatially and temporally by two crossed infrared lasers; a bifurcated fiber bundle is applied to receive the fluorescence spectra of 274-463 nm and 374-565 nm. Besides, with a 32-channel photomultiplier tube as detector, a self-developed combined spectrometer with Czerny-Turner design is employed to detect the two band spectra in a preset timing sequence. Experiments show that the system can detect the fluorescence spectra, after dual-wavelength-excitation, of three intrinsic fluorophore samples and three bioaerosol samples.

5.
J Fungi (Basel) ; 8(3)2022 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-35330300

RESUMO

True morels (Morchella, Pezizales) cultivated in soil are subject to complex influences from soil microbial communities. To explore the characteristics of soil microbial communities on morel cultivation, and evaluate whether these microbes are related to morel production, we collected 23 soil samples from four counties in Sichuan and Yunnan Provinces, China. Based on ITS and 16S rDNA amplicon sequencing, the alpha diversity analysis indicated that the biodiversity of morel cultivation soil showed a downward trend compared with the bare soil. The results also showed that there were no significant differences in soil microbial communities between OC (bare soil) and OO (after one-year suspension of sowing). This means that, after about one year of stopping sowing, the component and structure of soil that once cultivated morel would be restored. In co-occurrence networks, some noteworthy bacterial microbes involved in nitrogen fixation and nitrification have been identified in soils with high morel yields, such as Arthrobacter, Bradyhizobium, Devosia, Pseudarthrobacter, Pseudolabrys, and Nitrospira. In contrast, in soils with low or no morel yield, some pathogenic fungi accounted for a high proportion, including Gibberella, Microidium, Penicillium, Sarocladium, Streptomyces, and Trichoderma. This study provided valuable information for the isolation and culturing of some beneficial microbes for morel cultivation in further study and, potentially, to harness the power of the microbiome to improve morel production and health.

6.
Cancer Manag Res ; 14: 1113-1124, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35300064

RESUMO

Purpose: Autologous fat grafting (AFG) is a technique that can improve the appearance of breasts in surgical patients. There are currently few studies on breast-conserving surgery (BCS) combined with immediate AFG, although we believe that it could achieve satisfactory effects. Therefore, the purpose of this study is to observe the effects of BCS combined with immediate AFG on oncologic safety, satisfaction and psychology of breast cancer patients. Patients and Methods: We retrospectively collected the data of 85 breast cancer patients from February 2018 to October 2018. After screening, 40 patients in AFG group (AG, BCS combined with immediate AFG) and 40 patients in control group (CG, BCS alone) were finally included in the study. The primary outcomes were the survival, tumor recurrence and metastasis, and BREAST-Q score of patients. The secondary outcomes were short and long-term complications, degree of depression and anxiety of patients. Results: A total of 80 patients were included in the analysis. There was no significant difference in the clinicopathological data between the two groups (P>0.05). The average follow-up time of the two groups was 40.58±2.630 and 40.28±2.679 months. In the analysis of oncologic safety, no patients died in AG and 1 patient died in CG. In addition, there was no significant difference between the two groups in terms of the overall recurrence rate and the distribution of recurrence types (P>0.05). As for satisfaction, the BREAST-Q score of AG was significantly higher than that of CG (57.85±4.833 vs 51.93±5.045, P<0.001). In the secondary outcomes, there was no short-term complication specified in the study; in the long-term complications, the incidence of calcification in AG was not significantly higher than that in CG (P=0.065). In the analysis of depression and anxiety, there was no significant difference between the two groups (P>0.05). Conclusion: BCS combined with immediate AFG can significantly improve patients' satisfaction without increasing the risk of death and tumor recurrence. However, it does not seem to play a role in improving the conditions of depression and anxiety.

7.
Ann Transl Med ; 10(2): 107, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35282051

RESUMO

Background: In radiology, case reports play an important role in the presentation of a new disease or an unusual form of a common disease using radiological images. Radiology practitioners can refer to the CAse REport (CARE) statement to write and improve the quality of case reports; however, some CARE items are not applicable to the field of radiology. This protocol seeks to describe the methods and processes used to develop CARE extensions for radiology. Methods: We plan to extend the existing CARE guidelines to radiological case reports. We will follow the steps recommended by the Enhancing the QUAlity and Transparency Of health Research (EQUATOR) network to develop the CAse Report for Radiology (CARR) statement and checklist for the reporting of case reports. The working group will constitute a multidisciplinary international team of experts, including methodologists, content experts (radiologists and clinicians), journal editors, and possibly consumer representatives. We will discuss and generate a list of initial items based on the CARE statement. Two to three rounds of the Delphi survey will be administered and an online consensus meeting will be held to reach a consensus and develop the final CARR checklist. The full reporting guidelines should be finalized within 1.5 years. Discussion: The annual number of published radiological case reports has increased over the past 20 years; however, the quality of reporting still needs to be improved. Our protocol envisages the process and methodology for the development of the CARR guidelines, which we anticipate will be available soon and will help radiology practitioners. Trial Registration: We have registered the protocol on the EQUATOR network (https://www.equator-network.org/library/reporting-guidelines-under-development/reporting-guidelines-under-development-for-observational-studies/#CARR).

8.
Haematologica ; 2022 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-35354250

RESUMO

Bone marrow(BM) endothelial progenitor cell(EPC) damage with unknown mechanism delays the repair of endothelial cells(ECs) and hematopoiesis recovery after chemo-radiotherapy. Herein, enhanced glycolytic enzyme PFKFB3 was demonstrated in the damaged BM EPCs of patients with poor graft function(PGF), a clinical model of EPC damage-associated poor hematopoiesis after allogeneic hematopoietic stem cell transplantation(allo-HSCT). Moreover, glycolysis inhibitor 3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one(3PO) alleviated the damaged BM EPCs of PGF patients in vitro. Consistently, PFKFB3 overexpression triggered BM EPC damage after 5FU treatment and impaired hematopoiesis-supporting ability in vitro. Mechanismly, PFKFB3 facilitated pro-apoptotic transcription factor FOXO3A and its downstream gene expressions, including p21, p27, FAS after 5FU treatment in vitro. Moreover, PFKFB3 induced NF-κB activation and its downstream adhesion molecule E-selectin expression, while reduced hematopoietic factor SDF-1 expression, which could be rescued by FOXO3A silence. Highly expressed PFKFB3 was found in damaged BM ECs of chemo-radiotherapy-induced myelosuppression murine models. Furthermore, the BM EC-specific PFKFB3 overexpression murine model demonstrated that PFKFB3 aggravated BM EC damage, and impaired hematopoiesis recovery after chemotherapy in vivo, which could be improved by 3PO, indicating a critical role of PFKFB3 in regulating BM EC damage. Clinically, PFKFB3-induced FOXO3A expression and NF-κB activation were confirmed to contribute to the damaged BM EPCs of patients with acute leukemia after chemotherapy. 3PO repaired the damaged BM EPCs by reducing FOXO3A expression and phospho-NF-κB p65 in patients after chemotherapy. In summary, our results reveal a critical role of PFKFB3 in triggering BM EPC damage and indicate that endothelial-PFKFB3 may be a potential therapeutic target for myelosuppressive injury.

9.
J Neurotrauma ; 2022 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-35229653

RESUMO

This study investigates the effect of extended laminectomy (EL) on spinal cord injury (SCI) caused by spinal shortening, and further, the timing and the optimal length of removal. Dogs received spinal column shortening at T13 segment, following which the control group underwent regular laminectomy while other groups underwent laminectomy with an additional 1-lamina length removed 6h after shortening ("1-lamina EL 6 h"), an extra 1.5-lamina length resected at 6 h or 12 h after shortening ("1.5-lamina EL 6 h" and "1.5-lamina EL 12 h"), and an extra 2-lamina length removed at 6 or 12 h after shortening ("2-lamina EL 6 h" and 2-lamina EL 12 h"), respectively. Somatosensory evoked potential (SSEP) and neurological function were recorded periodically; spinal cord blood flow (SCBF) and nerve cell apoptosis were detected. The results showed that resection of an additional 1-lamina length appeared inadequate to relieve the sharp kinking of the spinal cord, whereas the kinking disappeared with an additional 2-lamina length resection. The "1-lamina EL 6 h" and "1.5-lamina EL 12 h" groups showed no significant differences from the control in latency of SSEP, SCBF, hindlimb function and apoptosis. By contrast, significant recovery of SSEP, SCBF and hindlimb function as well as reduction of apoptosis were presented in other three groups. The "2-lamina EL 6 h" group, in particular, showed the most prominent recovery. In conclusion, an additional resection of two laminae at 6 h after shortening showed the best effect in alleviating SCI. Timely and adequately extended laminectomy could be a potential therapeutic strategy for SCI attributable to spinal shortening.

10.
J Nanobiotechnology ; 20(1): 96, 2022 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-35236356

RESUMO

BACKGROUND: Despite extensive investigations on photothermal therapy, the clinical application is restricted due to poor stability, low therapeutic efficacy of photothermal therapy agents and its affinity loss in the multistep synthesis of delivery carriers. To address this, we designed an IR792-MCN@ZIF-8-PD-L1 siRNA (IM@ZP) nanoparticle drug delivery system. IM@ZP was prepared by in situ synthesis and physical adsorption, followed by characterization. Photothermal conversion ability of IM@ZP was assessed by irradiation of near-infrared (NIR) laser, followed by analysis of its effect on 4T1 cell viability, maturation of dendritic cells (DCs) and the secretion of related cytokines in vitro, and the changes of tumor infiltrating T cells and natural killer (NK) cells in vivo. Subcutaneous 4T1 tumor-bearing mouse and lung metastasis models were established to investigate the role of IM@ZP in killing tumor and inhibiting metastasis in vivo. RESULTS: IM@ZP was uniform nanoparticles of 81.67 nm with the characteristic UV absorption peak of IR792, and could effectively adsorb PD-L1 siRNA. Under the irradiation of 808 nm laser, IM@ZP exhibited excellent photothermal performance. IM@ZP could be efficiently uptaken by 4T1 cells, and had high transfection efficiency of PD-L1 siRNA. Upon NIR laser irradiation, IM@ZP effectively killed 4T1 cells, upregulated HSP70 expression, induced DC maturation and increased secretion of TNF-α and IL-6 in vitro. Moreover, in vivo experimental results revealed that IM@ZP enhanced photothermal immunotherapy as shown by promoted tumor infiltrating CD8 + and CD4 + T cells and NK cells, and inhibited tumor growth and lung metastasis. CONCLUSION: Together, biocompatible IM@ZP nanoparticles result in high photothermal immunotherapy efficiency and may have a great potential as a delivery system for sustained cancer therapy.


Assuntos
Nanopartículas , Neoplasias de Mama Triplo Negativas , Animais , Antígeno B7-H1 , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Sistemas de Liberação de Medicamentos , Humanos , Imunoterapia , Lasers , Camundongos , Fototerapia/métodos , RNA Interferente Pequeno/uso terapêutico , Neoplasias de Mama Triplo Negativas/tratamento farmacológico
11.
J Transl Med ; 20(1): 144, 2022 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-35351133

RESUMO

BACKGROUND: Myelodysplastic syndromes (MDS) are a group of heterogeneous myeloid clonal disorders characterized by ineffective haematopoiesis and immune deregulation. Emerging evidence has shown the effect of bone marrow (BM) endothelial progenitor cells (EPCs) in regulating haematopoiesis and immune balance. However, the number and functions of BM EPCs in patients with different stages of MDS remain largely unknown. METHODS: Patients with MDS (N = 30), de novo acute myeloid leukaemia (AML) (N = 15), and healthy donors (HDs) (N = 15) were enrolled. MDS patients were divided into lower-risk MDS (N = 15) and higher-risk MDS (N = 15) groups according to the dichotomization of the Revised International Prognostic Scoring System. Flow cytometry was performed to analyse the number of BM EPCs. Tube formation and migration assays were performed to evaluate the functions of BM EPCs. In order to assess the gene expression profiles of BM EPCs, RNA sequencing (RNA-seq) were performed. BM EPC supporting abilities of haematopoietic stem cells (HSCs), leukaemia cells and T cells were assessed by in vitro coculture experiments. RESULTS: Increased but dysfunctional BM EPCs were found in MDS patients compared with HDs, especially in patients with higher-risk MDS. RNA-seq indicated the progressive change and differences of haematopoiesis- and immune-related pathways and genes in MDS BM EPCs. In vitro coculture experiments verified that BM EPCs from HDs, lower-risk MDS, and higher-risk MDS to AML exhibited a progressively decreased ability to support HSCs, manifested as elevated apoptosis rates and intracellular reactive oxygen species (ROS) levels and decreased colony-forming unit plating efficiencies of HSCs. Moreover, BM EPCs from higher-risk MDS patients demonstrated an increased ability to support leukaemia cells, characterized by increased proliferation, leukaemia colony-forming unit plating efficiencies, decreased apoptosis rates and apoptosis-related genes. Furthermore, BM EPCs induced T cell differentiation towards more immune-tolerant cells in higher-risk MDS patients in vitro. In addition, the levels of intracellular ROS and the apoptosis ratios were increased in BM EPCs from MDS patients, especially in higher-risk MDS patients, which may be therapeutic candidates for MDS patients. CONCLUSION: Our results suggest that dysfunctional BM EPCs are involved in MDS patients, which indicates that improving haematopoiesis supporting ability and immuneregulation ability of BM EPCs may represent a promising therapeutic approach for MDS patients.


Assuntos
Células Progenitoras Endoteliais , Síndromes Mielodisplásicas , Apoptose , Medula Óssea , Células-Tronco Hematopoéticas , Humanos , Síndromes Mielodisplásicas/genética
12.
Sci Rep ; 12(1): 4745, 2022 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-35304534

RESUMO

Aerosol samplers are critical tools for studying indoor and outdoor aerosols. Development and evaluation of samplers is often labor-intensive and time-consuming due to the need to use monodisperse aerosols spanning a range of sizes. This study develops a rapid experimental methodology using polydisperse solid aerosols to evaluate size-resolved aerosol-to-aerosol (AtoA) and aerosol-to-hydrosol (AtoH) sampling efficiencies. Arizona Test Dust (diameter 0.5-20 µm) was generated and dispersed into an aerosol test chamber and two candidate samplers were tested. For the AtoA test, aerosols upstream and downstream of a sampler were measured using an online aerodynamic particle sizer. For the AtoH test, aerosols collected in sampling medium were mixed with a reference sample and then measured by the laser diffraction method. The experimental methodology were validated as an impressive time-saving procedure, with reasonable spatial uniformity and time stability of aerosols in the test chamber and an acceptable accuracy of absolute mass quantification of collected particles. Evaluation results showed that the AGI-30 and the BioSampler sampler had similar size-resolved sampling efficiencies and that efficiencies decreased with decreasing sampling flow rate. The combined evaluation of AtoA and AtoH efficiency provided more comprehensive performance indicators than either test alone. The experimental methodology presented here can facilitate the design and choice of aerosol sampler.


Assuntos
Poeira , Monitoramento Ambiental , Aerossóis/análise , Poeira/análise , Eficiência , Monitoramento Ambiental/métodos , Desenho de Equipamento , Tamanho da Partícula
13.
Am J Hematol ; 97(6): 762-769, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35293011

RESUMO

Adoptive therapy with cytomegalovirus (CMV)-specific cytotoxic T lymphocytes (CMV-CTLs) has emerged as an effective method for CMV infection. However, the efficacy reportedly ranges from 50% to 90%, and factors affecting anti-CMV efficacy have not been established. We investigated the safety and efficacy of adoptive therapy with CMV-CTLs for CMV infection in 190 patients after haploidentical stem cell transplantation (haplo-SCT), and importantly, we analyzed the main factors affecting antiviral efficacy. The CMV peak titer decreased from 19 (range, 1.0-503.0) × 103 copies/mL to 3.9 (range, 0-112) × 103 copies/mL after CMV-CTL infusion. The cumulative complete response (CR) rates in the first, fourth, and sixth weeks after the first CMV-CTL infusion were 37.9% (95% CI 35.0-40.8), 76.8% (95% CI 70.7-82.9), and 89.5% (95% CI 85.2-93.8), respectively. In multivariate analysis, persistent CMV infection prior to CMV-CTL infusion (hazard ratio [HR] 2.29, 95% CI 1.29-4.06, p = .005) and basiliximab treatment within 2 weeks of CMV-CTL infusion (HR 1.87, 95% CI 1.06-3.81, p = .031) were independent predictors of poor antiviral efficacy of CMV-CTL therapy. Our data showed that adoptive therapy with CMV-CTLs is a safe and effective treatment for CMV infection after haplo-SCT. Persistent CMV infection and basiliximab treatment are correlated with poor anti-CMV efficacy of CMV-CTL therapy.


Assuntos
Infecções por Citomegalovirus , Transplante de Células-Tronco Hematopoéticas , Antivirais/uso terapêutico , Basiliximab/uso terapêutico , Citomegalovirus , Infecções por Citomegalovirus/etiologia , Infecções por Citomegalovirus/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Transplante de Células-Tronco , Linfócitos T Citotóxicos
14.
Cancer Sci ; 2022 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-35178836

RESUMO

Evolutionarily conserved DDB1-and CUL4-associated factor 13 (DCAF13) is a recently discovered substrate receptor for the cullin RING-finger ubiquitin ligase 4 (CRL4) E3 ubiquitin ligase that regulates cell cycle progression. DCAF13 is overexpressed in many cancers, although its role in breast cancer is currently elusive. In this study we demonstrate that DCAF13 is overexpressed in human breast cancer and that its overexpression closely correlates with poor prognosis, suggesting that DCAF13 may serve as a diagnostic marker and therapeutic target. We knocked down DCAF13 in breast cancer cell lines using CRISPR/Cas9 and found that DCAF13 deletion markedly reduced breast cancer cell proliferation, clone formation, and migration both in vitro and in vivo. In addition, DCAF13 deletion promoted breast cancer cell apoptosis and senescence, and induced cell cycle arrest in the G1/S phase. Genome-wide RNAseq analysis and western blotting revealed that loss of DCAF13 resulted in both mRNA and protein accumulation of p53 apoptosis effector related to PMP22 (PERP). Knockdown of PERP partially reversed the hampered cell proliferation induced by DCAF13 knockdown. Co-immunoprecipitation assays revealed that DCAF13 and DNA damage-binding protein 1 (DDB1) directly interact with PERP. Overexpression of DDB1 significantly increased PERP polyubiquitination, suggesting that CRL4DCAF13 E3 ligase targets PERP for ubiquitination and proteasomal degradation. In conclusion, DCAF13 and the downstream effector PERP occupy key roles in breast cancer proliferation and potentially serve as prognostics and therapeutic targets.

15.
Front Immunol ; 13: 793382, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35154110

RESUMO

Pneumonic plague, caused by Yersinia pestis, is an infectious disease with high mortality rates unless treated early with antibiotics. Currently, no FDA-approved vaccine against plague is available for human use. The capsular antigen F1, the low-calcium-response V antigen (LcrV), and the recombinant fusion protein (rF1-LcrV) of Y. pestis are leading subunit vaccine candidates under intense investigation; however, the inability of recombinant antigens to provide complete protection against pneumonic plague in animal models remains a significant concern. In this study, we compared immunoprotection against pneumonic plague provided by rF1, rV10 (a truncation of LcrV), and rF1-V10, and vaccinations delivered via aerosolized intratracheal (i.t.) inoculation or subcutaneous (s.c.) injection. We further considered three vaccine formulations: conventional liquid, dry powder produced by spray freeze drying, or dry powder reconstituted in PBS. The main findings are: (i) rF1-V10 immunization with any formulation via i.t. or s.c. routes conferred 100% protection against Y. pestis i.t. infection; (ii) rF1 or rV10 immunization using i.t. delivery provided significantly stronger protection than rF1 or rV10 immunization via s.c. delivery; and (iii) powder formulations of subunit vaccines induced immune responses and provided protection equivalent to those elicited by unprocessed liquid formulations of vaccines. Our data indicate that immunization with a powder formulation of rF1-V10 vaccines via an i.t. route may be a promising vaccination strategy for providing protective immunity against pneumonic plague.


Assuntos
Vacina contra a Peste/imunologia , Peste/prevenção & controle , Vacinas de Subunidades/imunologia , Yersinia pestis/imunologia , Animais , Anticorpos Antibacterianos/sangue , Anticorpos Antibacterianos/imunologia , Modelos Animais de Doenças , Composição de Medicamentos , Ensaio de Imunoadsorção Enzimática , Feminino , Imunidade nas Mucosas , Imunização/métodos , Camundongos , Camundongos Endogâmicos BALB C , Especificidade de Órgãos , Peste/imunologia , Peste/mortalidade , Vacina contra a Peste/administração & dosagem , Vacina contra a Peste/química , Proteínas Recombinantes/imunologia , Mucosa Respiratória/imunologia , Vacinas de Subunidades/administração & dosagem , Vacinas de Subunidades/química
16.
Front Immunol ; 13: 819089, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35154137

RESUMO

Anthrax caused by Bacillus anthracis is a fatal zoonotic disease with a high lethality and poor prognosis. Inhalational anthrax is the most severe of the three forms of anthrax. The currently licensed commercial human anthrax vaccines require a complex immunization procedure for efficacy and have side effects that limit its use in emergent situations. Thus, development of a better anthrax vaccine is necessary. In this study, we evaluate the potency and efficacy of aerosolized intratracheal (i.t.) inoculation with recombinant protective antigen (rPA) subunit vaccines against aerosolized B. anthracis Pasteur II spores (an attenuated strain) challenge in a B10.D2-Hc0 mouse (deficient in complement component C5) model. Immunization of rPA in liquid, powder or powder reconstituted formulations via i.t. route conferred 100% protection against a 20× LD50 aerosolized Pasteur II spore challenge in mice, compared with only 50% of subcutaneous (s.c.) injection with liquid rPA. Consistently, i.t. inoculation of rPA vaccines induced a higher lethal toxin (LeTx) neutralizing antibody titer, a stronger lung mucosal immune response and a greater cellular immune response than s.c. injection. Our results demonstrate that immunization with rPA dry powder vaccine via i.t. route may provide a stable and effective strategy to improve currently available anthrax vaccines and B10.D2-Hc0 mice challenged with B. anthracis attenuated strains might be an alternative model for anthrax vaccine candidate screening.


Assuntos
Vacinas contra Antraz/imunologia , Antraz/prevenção & controle , Antígenos de Bactérias/imunologia , Toxinas Bacterianas/imunologia , Imunidade nas Mucosas , Vacinação/métodos , Administração Intranasal , Animais , Anticorpos Antibacterianos/sangue , Anticorpos Neutralizantes/sangue , Bacillus anthracis/imunologia , Feminino , Imunoglobulina G/sangue , Camundongos , Pós , Análise de Sobrevida , Vacinas de Subunidades/imunologia , Vacinas Sintéticas/imunologia
17.
J Anal Methods Chem ; 2022: 4208243, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35223127

RESUMO

Ginseng is a perennial herb with a long growth cycle and is known to easily accumulate pesticides during its growth process, seriously threatening people's health. Therefore, to ensure safe consumption, it is necessary to detect and monitor pesticide residues in ginseng. In this study, a novel analysis method was established for simultaneous determination of 31 pesticides in ginseng by high-performance liquid chromatography-mass spectrometry. Ginseng samples were extracted using acetonitrile, cleaned up by primary secondary amine (PSA) solid-phase extraction column eluted with acetonitrile-toluene, and then detected in multiple reaction mode (MRM). The calibration curves of target compounds were linear in the range of 0.005-1.0 mg/L, with correlation coefficients greater than 0.9921. The limits of detection of all the pesticides in ginseng were between 4.4×10-5 and 1.6 × 10-2 mg/kg. For fresh ginseng, the average recoveries ranged from 72.1 to 111.6%, and the relative standard deviations were 1.3-12.2%. For dry ginseng, the average recoveries were 74.3-108.3%, and the relative standard deviations were 0.9-14.9%. The residual concentrations of some pesticides in real samples were greater than the maximum residue limit (MRL) for European Union (EU). The method established here is rapid and simple with high sensitivity and good reproducibility, which is sensitive in the residue analysis of many pesticides in ginseng.

18.
BMJ Open ; 12(2): e053865, 2022 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-35149565

RESUMO

INTRODUCTION: Shivering is a common complication in the postoperative period. The incidence of shivering has been reported to range from 5% to 65% under general anaesthesia and as 33% during epidural anaesthesia. Shivering can increase perioperative risk in patients. Both dexmedetomidine and meperidine are effective agents for the prevention of postanaesthetic shivering. However, few studies have compared the anti-shivering effects of different agents following coronary artery bypass graft (CABG). This study aims to compare the effects of dexmedetomidine and meperidine on the incidence of shivering in patients undergoing CABG. METHODS AND ANALYSIS: A total of 180 patients aged 18-75 years, with an American Society of Anesthesiologists (ASA) grade of II-IV, undergoing elective CABG will be enrolled and randomly assigned to the dexmedetomidine, meperidine and control groups (placebo) in an intended 1:1:1 allocation ratio. The patients will be followed up for 7 days after surgery. The primary outcome is the incidence of shivering within 24 hours postoperatively. The secondary outcomes are the number of remedial drugs used after surgery, the incidence of postoperative hypotension and bradycardia, sedation scores, endotracheal extubation time, intensive care unit length of stay, incidence of postoperative delirium within 7 days after surgery, incidence of postoperative arrhythmias, incidence of postoperative nausea and vomiting, average hospital length of stay and mortality rate 30 days after surgery. ETHICS AND DISSEMINATION: The study protocol was approved by the ethics committee of The First Affiliated Hospital of Shandong First Medical University on 20 January 2021 (YXLL-KY-2021(002)) and registered at ClinicalTrials.gov. The results of this study will be presented at national and international scientific meetings and conferences. We plan to publish the data in peer-reviewed international scientific journals. TRIAL REGISTRATION NUMBER: NCT04735965.


Assuntos
Dexmedetomidina , Ponte de Artéria Coronária/efeitos adversos , Dexmedetomidina/uso terapêutico , Método Duplo-Cego , Humanos , Meperidina/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Tremor por Sensação de Frio
19.
Angew Chem Int Ed Engl ; 61(16): e202117368, 2022 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-35037708

RESUMO

Compounds bearing aliphatic amines can be emissive under appropriate conditions. However, their ionized counterparts, namely, quaternary ammonium salts (QASs), which are widely used as phase-transfer catalysts, ionic liquids, disinfectants, and surfactants, are known as luminescence quenchers and considered nonemissive. Herein, unprecedented intrinsic fluorescence/phosphorescence dual emissions from various QASs are reported, which can be finely regulated by changing the excitation wavelength, alkyl chain length, counterion, and mechanical stimuli. The bright photoluminescence along with distinct afterglow and tunable multicolor emissions enables the application of QAS solids in advanced multimode anticounterfeiting. This finding refreshes the understanding of QASs and may inspire emerging applications based on the utilization of the intrinsic luminescences of QASs. Furthermore, it opens opportunities for the investigation of QAS-related processes and functions via a photophysical approach and affords strong implications for the fabrication of novel nonconventional luminophores.

20.
Bone Marrow Transplant ; 57(4): 554-561, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35079139

RESUMO

The efficacy and outcome of therapeutic plasma exchange (TPE) for transplant-associated thrombotic microangiopathy (TA-TMA) remain controversial. We therefore sought to evaluate the outcome and efficacy of TPE in patients with TA-TMA and to identify TA-TMA patients who would benefit from TPE management. Eighty-two patients with TA-TMA were treated with TPE. We reported a response rate of 52% and overall survival rates of 20% and 15% at 100 days and 1 year after TA-TMA, respectively, in TPE-treated patients, with a significantly lower survival in gastrointestinal (GI) bleeding patients (5% vs. 41% in non-GI bleeding patients, P = 0.003). Multivariate analysis revealed that patients with GI bleeding, grade III-IV aGVHD, severe anemia, and a lower cumulative volume of TPE were less likely to respond to TPE. GI bleeding, a lower initial volume of TPE, and elevated total bilirubin were independently associated with 100-day mortality. The leading causes of death were infection, active TA-TMA, and MODS. The results of this large cohort of real-world practice indicate that the efficacy and outcome of TPE for TA-TMA patients without GI bleeding are encouraging, and a higher volume of TPE is warranted to achieve favorable outcomes.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Microangiopatias Trombóticas , Estudos de Coortes , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Troca Plasmática/efeitos adversos , Troca Plasmática/métodos , Microangiopatias Trombóticas/etiologia , Microangiopatias Trombóticas/terapia , Resultado do Tratamento
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