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1.
Artigo em Inglês | MEDLINE | ID: mdl-33646344

RESUMO

BACKGROUND: Subglottic squamous cell carcinoma (SCC) represents less than 5% of all laryngeal cancers. Our objective was to better characterize survival using the National Cancer Database (NCDB) registry from 2004 to 2015. RESULTS: 403 patients met inclusion criteria. 63.8% presented with advanced-stage disease. Treatment regimens were as follows: 15.9% underwent surgery alone, 16.9% underwent surgery followed by adjuvant therapy, and 67.2% underwent primary chemo/radiation (C/RT). Five-year overall survival (OS) was 58.6% for Stage I and II patients, 49.1% for Stage III, and 36.3% for stage IV. Adjusted OS for all-stage patients was worse with C/RT compared to upfront surgery (40.6% vs. 58.4%; HR 1.83 [95%CI 1.29-2.61] p < 0.001) and adjusted OS for stage 4 disease was significantly worse with C/RT compared to surgery (26.0% vs. 45.2%, HR 1.79 [95%CI 1.17-2.73] p = 0.007). CONCLUSION: Majority of patients were treated with primary C/RT. Adjusted survival favors upfront surgery versus C/RT, especially in patients with Stage IV disease.

2.
Blood Adv ; 5(5): 1154-1163, 2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33635333

RESUMO

The introduction of posttransplant cyclophosphamide (PTCy) made performing allogeneic hematopoietic cell transplantation (HCT) from HLA haplotype-incompatible donors possible. In a setting of PTCy and tacrolimus/mycophenolate mofetil (MMF) as a graft-versus-host disease (GVHD) prophylaxis, a peripheral blood (PB) graft source as compared with bone marrow reduces the relapse rate but increases acute GVHD (aGVHD) and chronic GVHD (cGVHD). This phase 2 trial assessed sirolimus and MMF efficacy following PTCy as a GVHD prophylaxis after PB haploidentical HCT (haplo-HCT). With 32 evaluable patients (≥18 years) enrolled, this study had 90% power to demonstrate a reduction in 100-day grade II-IV aGVHD to 20% from the historical benchmark of 40% after haplo-HCT using PTCy/tacrolimus/MMF. At a median follow-up of 16.1 months, the primary end point of the trial was met with a day-100 grade II-IV aGVHD cumulative incidence of 18.8% (95% confidence interval [CI], 7.5% to 34.0%). There were no graft-failure events and the 1-year probability of National Institutes of Health (NIH) moderate/severe cGVHD was 18.8% (95% CI, 7.4% to 34.0%), nonrelapse mortality was 18.8% (95% CI, 7.4% to 34.0%), relapse was 22.2% (95% CI, 9.6% to 38.2%), disease-free survival was 59.0% (95% CI, 44.1% to 79.0%), GVHD-free relapse-free survival was 49.6% (95% CI, 34.9% to 70.5%), and overall survival was 71.7% (95% CI, 57.7% to 89.2%) for the entire cohort. These data demonstrate that GVHD prophylaxis with sirolimus/MMF following PTCy effectively prevents grade II-IV aGVHD after PB haplo-HCT, warranting prospective comparison of sirolimus vs tacrolimus in combination with MMF following PTCy as GVHD prophylaxis after PB HCT. This trial was registered at www.clinicaltrials.gov as #NCT03018223.

3.
Nat Commun ; 12(1): 897, 2021 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-33563974

RESUMO

The dynamics, duration, and nature of immunity produced during SARS-CoV-2 infection are still unclear. Here, we longitudinally measured virus-neutralising antibody, specific antibodies against the spike (S) protein, receptor-binding domain (RBD), and the nucleoprotein (N) of SARS-CoV-2, as well as T cell responses, in 25 SARS-CoV-2-infected patients up to 121 days post-symptom onset (PSO). All patients seroconvert for IgG against N, S, or RBD, as well as IgM against RBD, and produce neutralising antibodies (NAb) by 14 days PSO, with the peak levels attained by 15-30 days PSO. Anti-SARS-CoV-2 IgG and NAb remain detectable and relatively stable 3-4 months PSO, whereas IgM antibody rapidly decay. Approximately 65% of patients have detectable SARS-CoV-2-specific CD4+ or CD8+ T cell responses 3-4 months PSO. Our results thus provide critical evidence that IgG, NAb, and T cell responses persist in the majority of patients for at least 3-4 months after infection.


Assuntos
Anticorpos Antivirais/imunologia , /virologia , Linfócitos T/imunologia , Adulto , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Imunoglobulina M/sangue , Imunoglobulina M/imunologia , Memória Imunológica , Interferon gama/metabolismo , Cinética , Antígenos Comuns de Leucócito/metabolismo , Masculino , Pessoa de Meia-Idade , Fenótipo , Receptores CCR7/metabolismo
4.
Int J Biol Sci ; 17(2): 498-513, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33613108

RESUMO

Long noncoding RNA DiGeorge syndrome critical region gene 5 (DGCR5) has been shown to be highly associated with cancer development. However, the biological role and molecular mechanism of DGCR5 in pancreatic cancer (PC) remains largely unknown. This study aimed to explore the role of DGCR5 in PC. It was revealed that DGCR5 was highly expressed in PC tissues compared with adjacent normal tissues and was associated with poor prognosis in PC patients. Furthermore, DGCR5 depletion inhibited the proliferation, migration and invasion by increasing apoptosis and inducing G0/G1 cell cycle arrest in vitro. Moreover, xenograft assay validated that DGCR5 promotes PC tumor growth in vivo. Mechanistically, DGCR5 was found to act as a ceRNA by sponging miR-3163 to regulate DNA topoisomerase 2-alpha (TOP2A) and inhibit Wnt/ß-catenin pathway. In addition, it was found that DGCR5 downregulation could enhance the sensitivity of PC cells to gemcitabine, and ChIP assay showed that PAX5 (Paired Box 5) could bind to the promoter region of DGCR5 and increase its transcription. The results of the present study indicated that DGCR5 may be a potential diagnostic biomarker and therapeutic target for PC.

5.
Chem Commun (Camb) ; 57(18): 2301-2304, 2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33533348

RESUMO

Manganese formate complexes, HMn(η2-O2CH) and Mn(η2-O2CH), are formed through MnH2 and MnH reactions with CO2 in solid parahydrogen and identified by matrix infrared spectroscopy with the basis of isotopic substitutions and theoretical frequency calculations. The reaction mechanism has been proposed that the reaction proceeds by concerted hydride ion transfer.

6.
Clin Appl Thromb Hemost ; 27: 1076029621989811, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33587652

RESUMO

Antihemophilic factor (recombinant) (rAHF; ADVATE®; Baxalta US Inc., a Takeda company, Lexington, MA, USA) is indicated for the treatment and prevention of bleeding in patients with hemophilia A. We aimed to assess the safety and efficacy of standard prophylaxis versus on-demand treatment with rAHF in previously treated Chinese patients with severe/moderately severe hemophilia A. This open-label, sequential, interventional, postapproval study (NCT02170402) conducted in China included patients of any age with hemophilia A with factor VIII (FVIII) level ≤2%. Patients received 6 months' on-demand rAHF then 6 months' rAHF prophylaxis (20-40 IU/kg every 48 ± 6 hours). The primary objective was percentage reduction in annualized bleeding rate (ABR) in the per-protocol analysis set (PPAS); secondary objectives included ABR by bleeding subtype, hemostatic efficacy, immunogenicity, and safety. Of 72 patients who received ≥1 rAHF dose, 61 were included in the PPAS. Total ABR was lower during prophylaxis (mean 2.5, 95% CI 1.5-3.7; median 0) versus on-demand treatment (mean 58.3, 95% CI 52.5-64.7; median 53.9), representing a 95.9% risk reduction. Similar findings in favor of prophylaxis were observed for all types of bleeding event by cause and location. rAHF hemostatic efficacy was rated as "excellent"/"good" in 96.1% of treated bleeding events. Transient FVIII inhibitors (0.6-1.7 BU) in 4 patients resolved before study end; no unexpected safety issues were observed. rAHF prophylaxis in this study of previously treated Chinese patients with severe/moderately severe hemophilia A resulted in a clear reduction in bleeding events versus rAHF on-demand treatment, with no change in safety profile.


Assuntos
Coagulantes/administração & dosagem , Fator VIII/administração & dosagem , Hemofilia A/tratamento farmacológico , Hemorragia/prevenção & controle , Adolescente , Adulto , Criança , Pré-Escolar , China , Coagulantes/efeitos adversos , Coagulantes/farmacocinética , Esquema de Medicação , Fator VIII/efeitos adversos , Fator VIII/farmacocinética , Hemofilia A/sangue , Hemofilia A/complicações , Hemofilia A/diagnóstico , Hemorragia/etiologia , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Vigilância de Produtos Comercializados , Estudos Prospectivos , Proteínas Recombinantes/administração & dosagem , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
7.
Artigo em Inglês | MEDLINE | ID: mdl-33527445

RESUMO

Inflammatory bowel disease (IBD) is a chronic progressive disorder characterized by complicated gastrointestinal inflammation. Research on therapeutic agents is still urgent due to the lack of satisfactory treatments. Gut macrophages are considered to be predominant in excessive inflammatory responses. Thus, we aimed to investigate whether depletion of macrophages would have a beneficial effect on IBD and could be a potential therapeutic strategy. In this study, we established a 12-day Dextran sodium sulphate (DSS)-induced colitis mouse model and determined the effect of the macrophage depletion agent Clophosome (neutral clodronate liposomes; CNC). The results showed that CNC significantly alleviated the symptoms of colitis, as demonstrated by greater weight gain, decreased disease activity index (DAI) scores, and lower histopathological damage scores, as well was reduced levels of the proinflammatory cytokines interleukin (IL)-6 and tumour necrosis factor (TNF)-α. To investigate T cell subsets, cells were isolated from the lamina propria and cultured to analyse the expression of IL-17A, interferon (IFN)-γ and Foxp3 in CD4+ cells by flow cytometry. The data showed that during the process of colitis, the frequencies of CD4+ IL-17A+ T cells were significantly increased. Notably, CNC treatment markedly reduced the population of CD4+ IL-17A+ T cells, especially CD4+ IL-17A+ IFN-γ+ T cells. Furthermore, intestinal barrier integrity, as assessed by immunostaining of mucin and tight junction proteins, was severely disrupted in colitis. CNC improved the intestinal barrier by enhancing the expression of muc-2 and occludin. In summary, our findings demonstrated that CNC successfully ameliorated DSS-induced colitis and that its effect may be associated with inhibiting inflammatory responses and maintaining intestinal integrity.

8.
Artigo em Inglês | MEDLINE | ID: mdl-33387310

RESUMO

A novel eco-friendly molecularly imprinted polymer (MIP) was proposed as solid-phase extraction (SPE) adsorbent to selective adsorption tylosin (TYL) in animal muscle samples. The MIP was synthesized in aqueous by using 1,4-butanediyl-3,3-bis-1-vinyl imidazolium chloride and 2-acrylamide-2-methylpropanesulfonic acid as bifunctional monomer. The obtained MIP had excellent selectivity towards TYL in water, and the maximum binding capacity can reach 123.45 mg g-1. Combined with high-performance liquid chromatography, the presented MIP can be used as SPE sorbent to recognize and detect TYL in the range of 0.008 to 0.6 mg L-1 (R2 = 0.9995). The limit of detection and limit of quantification were 0.003 mg L-1 and 0.008 mg L-1, and the intraday and interday precision were 1.05% and 3.36%, respectively. Under the optimal condition, the established MIP-SPE-HPLC method was successfully applied to separate and determine trace TYL in chicken, pork, and beef samples with satisfactory recoveries ranged from 94.0 to 106.3%, and the MIP-SPE cartridge can be cycled at least 20 times. This study implies a promising green MIP-SPE-HPLC method for highly selective adsorption and analysis trace TYL in complex matrices.

9.
Stem Cell Res Ther ; 12(1): 4, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33407872

RESUMO

BACKGROUND: As one of the main functional forms of mesenchymal stem cells (MSCs), MSC-derived extracellular vesicles (MSC-EVs) have shown an alternative therapeutic option in experimental models of allergic asthma. Oxygen concentration plays an important role in the self-renewal, proliferation, and EV release of MSCs and a recent study found that the anti-asthma effect of MSCs was enhanced by culture in hypoxic conditions. However, the potential of hypoxic MSC-derived EVs (Hypo-EVs) in asthma is still unknown. METHODS: BALB/c female mice were sensitized and challenged with ovalbumin (OVA), and each group received PBS, normoxic human umbilical cord MSC-EVs (Nor-EVs), or Hypo-EVs weekly. After treatment, the animals were euthanized, and their lungs and bronchoalveolar lavage fluid (BALF) were collected. With the use of hematoxylin and eosin (HE), periodic acid-Schiff (PAS) and Masson's trichrome staining, enzyme-linked immune sorbent assay (ELISA), Western blot analysis, and real-time PCR, the inflammation and collagen fiber content of airways and lung parenchyma were investigated. RESULTS: Hypoxic environment can promote human umbilical cord MSCs (hUCMSCs) to release more EVs. In OVA animals, the administration of Nor-EVs or Hypo-EVs significantly ameliorated the BALF total cells, eosinophils, and pro-inflammatory mediators (IL-4 and IL-13) in asthmatic mice. Moreover, Hypo-EVs were generally more potent than Nor-EVs in suppressing airway inflammation in asthmatic mice. Compared with Nor-EVs, Hypo-EVs further prevented mouse chronic allergic airway remodeling, concomitant with the decreased expression of pro-fibrogenic markers α-smooth muscle actin (α-SMA), collagen-1, and TGF-ß1-p-smad2/3 signaling pathway. In vitro, Hypo-EVs decreased the expression of p-smad2/3, α-SMA, and collagen-1 in HLF-1 cells (human lung fibroblasts) stimulated by TGF-ß1. In addition, we showed that miR-146a-5p was enriched in Hypo-EVs compared with that in Nor-EVs, and Hypo-EV administration unregulated the miR-146a-5p expression both in asthma mice lung tissues and in TGF-ß1-treated HLF-1. More importantly, decreased miR-146a-5p expression in Hypo-EVs impaired Hypo-EV-mediated lung protection in OVA mice. CONCLUSION: Our findings provided the first evidence that hypoxic hUCMSC-derived EVs attenuated allergic airway inflammation and airway remodeling in chronic asthma mice, potentially creating new avenues for the treatment of asthma.

10.
Spectrochim Acta A Mol Biomol Spectrosc ; 251: 119457, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33485241

RESUMO

The unbalanced metabolism of sulfur dioxide can cause various diseases, such as neurological disorders and lung cancer. Until now, some researches revealed that the normal function of lysosomes would be disrupted by its abnormal viscosity. As a signal molecule, sulfur dioxide (SO2) plays an important role in lysosome metabolism. However, the connection of metabolism between the SO2 and viscosity in lysosomes is still unknown. Herein, we developed a benzothiazole-based near-infrared (NIR) fluorescent probe (Triph-SZ), which can monitor the SO2 derivatives and respond to the change of viscosity in lysosomes through two-photon imaging. Triph-SZ present high sensitivity and selectivity fluorescence response with the addition of SO2 derivatives based on the nucleophilic addition, and it also exhibits a sensitive fluorescence enhancement to environmental viscosity, which allows Triph-SZ to be employed to monitor the level of HSO3- and viscosity changes in lysosomes by the two-photon fluorescence lifetime imaging microscopy.

11.
Food Chem ; 347: 129013, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-33482481

RESUMO

The effective analysis of cephalosporin antibiotics in food animals has attracted considerable attention. Herein, a high-performance liquid chromatograph equipped with a UV method based on molecularly imprinted-solid phase extraction (MISPE-HPLC-UV) was developed for preconcentration, cleanup and determination of ceftiofur sodium (CTFS) in food samples. In this method, an eco-friendly molecularly imprinted polymer (MIP) was synthesized and employed as an adsorbent, which exhibited excellent selectivity towards CTFS in water, and adsorption equilibrium could be reached within 1 h. Under the optimized conditions, good linearity was obtained for CTFS in the range of 0.005-1.0 mg L-1 with a lower LOD of 0.0015 mg L-1, and the average recoveries were higher than 91.9% (RSD less than 8.5%) at three spiked levels in milk, chicken, pork and beef samples. After 20 cycles, the recovery of the MISPE cartridge for CTFS was still higher than 95%, which proved that the MISPE-HPLC-UV method was highly sensitive and selective for the analysis of CTFS in food samples.

12.
Int J Biol Macromol ; 171: 539-549, 2021 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-33434550

RESUMO

The present study aimed to investigate the biological functions of germinated M. oleifera seed proteins and to identify the identity of milk-clotting proteases. A total of 963 proteins were identified, and those with molecular weights between 10 and 30 kDa were most abundant. The identified proteins were mainly involved in energy-associated catalytic activity and metabolic processes, and carbohydrate and protein metabolisms. The numbers of proteins associated with the hydrolytic and catalytic activities were higher than the matured dry M. oleifera seeds reported previously. Of the identified proteins, proteases were mainly involved in the milk-clotting activity. Especially, a cysteine peptidase with a molecular mass of 17.727 kDa exhibiting hydrolase and peptidase activities was purified and identified. The identified cysteine peptidase was hydrophilic, and its secondary structure consisted of 27.60% alpha helix, 9.20% beta fold, and 63.20% irregular curl; its tertiary structure was also constructed using M. oleifera seed 2S protein as the protein template. The optimal pH and temperature of the purified protease were pH 4.0 and 60 °C, respectively. The protease had high acidic stability and good thermostability, thus could potentially be applied in the dairy industry.

13.
Blood ; 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33512407

RESUMO

Axicabtagene ciloleucel (axi-cel) is a chimeric antigen receptor (CAR) T cell therapy for relapsed or refractory large B cell lymphoma (LBCL). Here, we evaluated whether immune dysregulation, present prior to CAR-T cell therapy, associated with treatment failure. Tumor expression of interferon (IFN) signaling, high blood levels of monocytic myeloid-derived suppressor cells (M-MDSCs), and high blood IL-6 and ferritin each associated with a lack of durable response. Similar to other cancers, we found that in LBCL tumor IFN signaling is associated with the expression of multiple checkpoint ligands including PD-L1, and these were higher in patients who lacked durable responses to CAR-T therapy. Moreover, tumor IFN signaling and blood M-MDSCs associated with decreased axi-cel expansion. Finally, patients with high tumor burden had higher immune dysregulation with increased serum inflammatory markers and tumor IFN signaling. These data support that immune dysregulation in LBCL promotes axi-cel resistance via multiple mechanistic programs: insufficient axi-cel expansion associated with both circulating M-MDSC and tumor IFN signaling, that also gives rise to expression of immune checkpoint ligands.

14.
J Investig Med ; 69(2): 377-381, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33310761

RESUMO

Previous studies have reported that as the main extract of areca nut, arecoline (ARE) causes DNA damage and in turn contributes to the carcinogenesis of oral epithelial cells. It has been reported that ARE can inhibit the expression of miR-886-3p. In the current study, we aimed to explore the expression and biological functions of miR-886-3p in oral squamous cell carcinoma (OSCC). Herein, we demonstrated that in OSCC cells treated with ARE, the expression level of miR-886-3p was negatively correlated with the concentration of ARE. Compared with adjacent tissue, the expression level of miR-886-3p in OSCC tissue was remarkably downregulated. Transfection of miR-886-3p mimics markedly decreased viability, migration and invasion of OSCC cells. These experimental data implied that miR-886-3p suppression mediated by ARE took part in the proliferation and metastasis of OSCC. This study can help elucidate the mechanism by which areca nut chewing contributes to the malignant transformation of oral epithelial cells.

15.
Mol Carcinog ; 60(2): 138-150, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33378592

RESUMO

Prognosis for patients with recurrent and/or metastatic head and neck squamous cell carcinoma (HNSCC) remains poor. Development of more effective and less toxic targeted therapies is necessary for HNSCC patients. Checkpoint kinase 1 (CHK1) plays a vital role in cell cycle regulation and is a promising therapeutic target in HNSCC. Prexasertib, a CHK1 inhibitor, induces DNA damage and cell death, however, its effect on the tumor immune microenvironment (TIME) is largely unknown. Therefore, we evaluated a short-term and long-term effects of prexasertib in HNSCC and its TIME. Prexasertib caused increased DNA damage and cell death in vitro and significant tumor regression and improved survival in vivo. The gene expression and multiplex immunohistochemistry (mIHC) analyses of the in vivo tumors demonstrated increased expression of genes that are related to T-cell activation and increased immune cell trafficking, and decreased expression of genes that related to immunosuppression. However, increased expression of genes related to immunosuppression emerged over time suggesting evasion of immune surveillances. These findings in gene expression analyses were confirmed using mIHC which showed differential modulation of TIME in the tumor margins and as well as cores over time. These results suggest that evasion of immune surveillance, at least in part, may contribute to the acquired resistance to prexasertib in HNSCC.

16.
Phys Chem Chem Phys ; 23(1): 528-535, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33325467

RESUMO

We investigate the hydrolysis of vanadium/niobium monoxide cation (VO+/NbO+) with water molecules in the gas phase. Cationic argon-tagged intermediates, TMO(H2O)nArm+ (TM = V, Nb; n = 1-2, m = 1-2), are prepared for examination using infrared photodissociation spectroscopy. The structures of the intermediates are elucidated by comparing them with simulated spectra. VO(H2O)Ar+ or NbO(H2O)Ar+ (for n = 1) is intrinsically a hydrated adduct, represented by H2O-VOAr+ or H2O-NbOAr+, rather than a dihydroxide, V(OH)2Ar+ or Nb(OH)2Ar+. However, when a second H2O molecule is involved (for n = 2), the dihydroxide V(OH)2(H2O)Ar+ and trihydroxide HNb(OH)3Ar+ are formed. In this process, the six-member cyclic transition state formed by two H2O molecules markedly reduces the hydrogen transfer energy barrier based on our calculations. This work provides more precise experimental evidence for the Grotthuss-like mechanism proposed in the studies of hydrolysis and tautomerization reactions.

17.
Clin Transl Allergy ; 10(1): 50, 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33292509

RESUMO

BACKGROUND: Artemisia weed pollen allergy is important in the northern hemisphere. While over 350 species of this genus have been recorded, there has been no full investigation into whether different species may affect the allergen diagnosis and treatment. This study aimed to evaluate the variations in amino acid sequences and the content of major allergens, and how these affect specific IgE binding capacity in representative Artemisia species. METHODS: Six representative Artemisia species from China and Artemisia vulgaris from Europe were used to determine allergen amino acid sequences by transcriptome, gene sequencing and mass spectrometry of the purified allergen component proteins. Sandwich ELISAs were developed and applied for Art v 1, Art v 2 and Art v 3 allergen quantification in different species. Aqueous pollen extracts and purified allergen components were used to assess IgE binding by ELISA and ImmunoCAP with mugwort allergic patient serum pools and individual sera from five areas in China. RESULTS: The Art v 1 and Art v 2 homologous allergen sequences in the seven Artemisia species were highly conserved. Art v 3 type allergens in A. annua and A. sieversiana were more divergent compared to A. argyi and A. vulgaris. The allergen content of Art v 1 group in the seven extracts ranged from 3.4% to 7.1%, that of Art v 2 from 1.0% to 3.6%, and Art v 3 from 0.3% to 10.5%. The highest IgE binding potency for most Chinese Artemisia allergy patients was with A. annua pollen extract, followed by A. vulgaris and A. argyi, with A. sieversiana significantly lower. Natural Art v 1-3 isoallergens from different species have almost equivalent IgE binding capacity in Artemisia allergic patients from China. CONCLUSION AND CLINICAL RELEVANCE: There was high sequence similarity but different content of the three group allergens from different Artemisia species. Choice of Artemisia annua and A. argyi pollen source for diagnosis and immunotherapy is recommended in China.

18.
Am J Cancer Res ; 10(11): 3622-3643, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33294258

RESUMO

Estrogen-related receptor alpha (ERRα), an orphan nuclear receptor, was reported to be highly associated with the progression and tumorigenesis of several human malignancies. However, the biological role and underlying molecular mechanisms of ERRα in pancreatic cancer (PC) remain unknown. The present study demonstrated that ERRα was significantly overexpressed in PC tissues and cell lines. Its high expression was correlated with tumor size, distant metastasis, TNM stage, tumor differentiation and poor prognosis of PC. Subsequent functional assays showed that ERRα promoted PC cell proliferation, tumor growth, as well as migration and invasion via activating the epithelial-mesenchymal transition. In addition, knockdown of ERRα induced apoptosis and G0/G1 cell cycle arrest in PC cells. Plasminogen activator inhibitor 1 (PAI1) was identified by RNA sequencing, knockdown of which could suppress the cell proliferation, migration and invasion that promoted by ERRα overexpression. Further mechanistic investigation using chromatin immunoprecipitation and dual-luciferase reporter assays revealed that ERRα could bind to the PAI1 promoter region and transcriptionally enhance PAI1 expression. Moreover, our data indicated that ERRα played its oncogenic role in PC via activating the MEK/ERK pathway. Taken together, our study demonstrates that ERRα promotes PC progression by enhancing the transcription of PAI1 and activation of the MEK/ERK pathway, pointing to ERRα as a novel diagnostic and therapeutic target for PC.

19.
Plant Signal Behav ; : 1850627, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33258712

RESUMO

Cryptochrome (CRY) is a blue light receptor that is widely distributed in animals, plants, and microorganisms. CRY as a coding gene of cryptochrome that regulates the organism gene expression and plays an important role in organism growth and development. In this study, we identified four photolyase/cryptochrome (PHR/CRY) members from the genome of Ginkgo biloba. Phylogenetic tree analysis showed that the Ginkgo PHR/CRY family members were closely related to Arabidopsis thaliana and Solanum lycopersicum. We isolated a cryptochrome gene, GbCRY1, from G. biloba and analyzed its structure and function. GbCRY1 shared high similarity with AtCRY1 from A. thaliana. GbCRY1 expression level was higher in stems and leaves and lower in roots, male strobili, female strobili. GbCRY1 expression level fluctuated periodically within 24 h, gradually increased in the dark, and decreased under blue light. The newly germinated ginkgo seedlings were cultured under dark, white light, and blue light conditions. The blue light normally induced photomorphogenesis of ginkgo seedlings, which included hypocotyl elongation inhibition, leaf expansion inhibition, and chlorophyll formation. Treating dark-adapted ginkgo leaves with blue light could induce stomatal opening. At the same time, blue light reduced the expression level of GbCRY1 in the process of inducing photomorphogenesis and stoma opening. Our results provide evidence that GbCRY1 expression is affected by space, circadian cycle and light, and also proves that GbCRY1 is related to ginkgo circadian clock, photomorphogenesis and stoma opening process.

20.
J Blood Med ; 11: 439-448, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33269010

RESUMO

Introduction: Moroctocog alfa albumin-free cell culture (AF-CC) increases plasma levels of factor VIII (FVIII) activity and, in China, is indicated for the control and prevention of bleeding episodes in patients with hemophilia A. This study aimed to evaluate the efficacy, safety, and recovery data of moroctocog alfa (AF-CC) in patients with hemophilia participating in two open-label studies, both conducted in China. Methods: The authorization study (clinicaltrials.gov identifier NCT00868530) enrolled patients aged ≥6 years, previously treated with ≥1 exposure day of FVIII replacement therapy. The real-world study (clinicaltrials.gov identifier NCT02492984) enrolled patients of any age who were previously untreated or requiring surgical prophylaxis. In both studies, on-demand treatment was administered over 6 months. Key assessments included response to treatment, FVIII inhibitor development, and recovery. Results: In the authorization study (N = 53; mean age, 23.2 years; severe hemophilia, 23%), response was excellent/good for 90% of infusions at 24 hours. Seven patients developed inhibitors. Mean (SD) FVIII recovery at the initial and final visits was 1.77 (0.50) and 1.67 (0.45) (IU/dL)/(IU/kg), respectively. In the real-world study (N = 85; mean age, 9.5 years; severe hemophilia, 58%), response was rated as excellent or good for most (87%) on-demand infusions and for all surgical prophylaxis patients (n = 14). Seven patients developed FVIII inhibitors. Mean (SD) FVIII recovery at the initial and final visits was 1.71 (0.50) and 1.68 (0.31) (IU/dL)/(IU/kg), respectively. No new safety signals were observed in either study. Conclusion: On-demand treatment and surgical prophylaxis with moroctocog alfa (AF-CC) is safe and effective for both previously treated and previously untreated Chinese patients with hemophilia A.

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