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1.
Chem Asian J ; 16(4): 342-347, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33427391

RESUMO

Mitochondrial pH is an important factor associated with cellular metabolism and pathological states. Thus, sensitively monitoring its minor change was essential. However, it was challengeable due to the lack of suitable probes. Here, a mitochondria-targeted probe (NIR-OH-1) was synthesized. Based on the protonation/deprotonation of the hydroxy group and the assistance of carboxyl group on NIR-OH-1 molecular structure, a dramatic NIR activated signal was generated for sensing pH. Probe NIR-OH-1 displayed a good photo-stability and reversibility and could detect pH change without interference by other biologically active species. Importantly, NIR-OH-1 had an appropriate pKa value (7.77) and tiny acid-base transition range, which was allowed to map the small pH changes of cellular mitochondrial. Moreover, NIR-OH-1 was also successfully applied in real-time monitoring mitochondrial pH-related pathological events in living cells under different stimulation, demonstrating the prospect of its clinical application in accurate mitochondrial pH detection under related physiological and pathological conditions.

2.
J Exp Med ; 218(3)2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33496784

RESUMO

The antitumor effects of ionizing radiation (IR) are mediated in part through activation of innate and adaptive immunity. Here we report that gut microbiota influences tumor control following IR. Vancomycin decreased the abundance of butyrate-producing gut bacteria and enhanced antitumor responses to IR. Oral administration of Lachnospiraceae, a family of vancomycin-sensitive bacteria, was associated with increased systemic and intratumoral butyric acid levels and impaired the efficacy of IR in germ-free (GF) mice. Local butyrate inhibited STING-activated type I IFN expression in dendritic cells (DCs) through blockade of TBK1 and IRF3 phosphorylation, which abrogated IR-induced tumor-specific cytotoxic T cell immune responses without directly protecting tumor cells from radiation. Our findings demonstrate that the selective targeting of butyrate-producing microbiota may provide a novel therapeutic option to enhance tumor radiation sensitivity.

3.
Anesthesiology ; 134(3): 381-394, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33439974

RESUMO

BACKGROUND: Delayed neurocognitive recovery after surgery is associated with poor outcome. Most surgeries require general anesthesia, of which sevoflurane and propofol are the most commonly used inhalational and intravenous anesthetics. The authors tested the primary hypothesis that patients with laparoscopic abdominal surgery under propofol-based anesthesia have a lower incidence of delayed neurocognitive recovery than patients under sevoflurane-based anesthesia. A second hypothesis is that there were blood biomarkers for predicting delayed neurocognitive recovery to occur. METHODS: A randomized, double-blind, parallel, controlled study was performed at four hospitals in China. Elderly patients (60 yr and older) undergoing laparoscopic abdominal surgery that was likely longer than 2 h were randomized to a propofol- or sevoflurane-based regimen to maintain general anesthesia. A minimum of 221 patients was planned for each group to detect a one-third decrease in delayed neurocognitive recovery incidence in propofol group compared with sevoflurane group. The primary outcome was delayed neurocognitive recovery incidence 5 to 7 days after surgery. RESULTS: A total of 544 patients were enrolled, with 272 patients in each group. Of these patients, 226 in the propofol group and 221 in the sevoflurane group completed the needed neuropsychological tests for diagnosing delayed neurocognitive recovery, and 46 (20.8%) in the sevoflurane group and 38 (16.8%) in the propofol group met the criteria for delayed neurocognitive recovery (odds ratio, 0.77; 95% CI, 0.48 to 1.24; P = 0.279). A high blood interleukin-6 concentration at 1 h after skin incision was associated with an increased likelihood of delayed neurocognitive recovery (odds ratio, 1.04; 95% CI, 1.01 to 1.07; P = 0.007). Adverse event incidences were similar in both groups. CONCLUSIONS: Anesthetic choice between propofol and sevoflurane did not appear to affect the incidence of delayed neurocognitive recovery 5 to 7 days after laparoscopic abdominal surgery. A high blood interleukin-6 concentration after surgical incision may be an independent risk factor for delayed neurocognitive recovery.

5.
Blood ; 136(25): 2905-2917, 2020 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-33331927

RESUMO

T-cell responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been described in recovered patients, and may be important for immunity following infection and vaccination as well as for the development of an adoptive immunotherapy for the treatment of immunocompromised individuals. In this report, we demonstrate that SARS-CoV-2-specific T cells can be expanded from convalescent donors and recognize immunodominant viral epitopes in conserved regions of membrane, spike, and nucleocapsid. Following in vitro expansion using a good manufacturing practice-compliant methodology (designed to allow the rapid translation of this novel SARS-CoV-2 T-cell therapy to the clinic), membrane, spike, and nucleocapsid peptides elicited interferon-γ production, in 27 (59%), 12 (26%), and 10 (22%) convalescent donors (respectively), as well as in 2 of 15 unexposed controls. We identified multiple polyfunctional CD4-restricted T-cell epitopes within a highly conserved region of membrane protein, which induced polyfunctional T-cell responses, which may be critical for the development of effective vaccine and T-cell therapies. Hence, our study shows that SARS-CoV-2 directed T-cell immunotherapy targeting structural proteins, most importantly membrane protein, should be feasible for the prevention or early treatment of SARS-CoV-2 infection in immunocompromised patients with blood disorders or after bone marrow transplantation to achieve antiviral control while mitigating uncontrolled inflammation.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Técnicas de Cultura de Células/métodos , Imunoterapia Adotiva/métodos , /imunologia , Adulto , Idoso , Epitopos de Linfócito T/imunologia , Feminino , Humanos , Epitopos Imunodominantes/imunologia , Masculino , Proteínas de Membrana/imunologia , Pessoa de Meia-Idade , Proteínas Virais/imunologia , Adulto Jovem
6.
Front Immunol ; 11: 580335, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33224142

RESUMO

Background: The programmed cell death ligand 1 (PD-L1) plays a key role in glioma development. However, due to the specificity of glioma's anatomical position, the role of its expression as a tumor biomarker is limited. It has been proven that the levels of soluble programmed death-ligand 1 (sPD-L1) are associated with prognosis in many malignancies including glioma. However, the expression of sPD-L1 in glioma patients receiving radiotherapy (RT) remains unclear. The purpose of this study was to evaluate the concentration of sPD-L1 in the plasma of glioma patients before and after RT and to explore its relationship with clinical outcomes. Methods: Between October 2017 and September 2018, glioma patients treated with RT (30 ± 10 Gy, 2 Gy/f) were enrolled, and blood samples were collected before and after RT. We quantified the sPD-L1 levels by enzyme-linked immunosorbent assay (ELISA). The isocitrate dehydrogenase-1 (IDH-1) mutational status and Ki-67 expression of tumors were evaluated by immunohistochemistry. Glioma murine model were used to address whether circulating sPD-L1 molecules are directly targeted by an anti-PD-L1 antibody. The associations between sPD-L1 and clinical features were assessed with Pearson's or Spearman's correlation analysis. The progression-free survival (PFS) and overall survival (OS) were determined by the Kaplan-Meier method. Results: Sixty glioma patients were included, with a median age of 52 years. The proportions of grade I, II, III, and IV gliomas were 6.7%, 23.3%, 28.4%, and 41.6%, respectively. The baseline sPD-L1 levels were significantly associated with tumor grade, IDH-1 mutation status and Ki-67 expression. Using 14.35 pg/ml as the cutoff, significantly worse PFS and OS were both observed in patients with higher baseline levels of sPD-L1 (P = 0.027 and 0.008, respectively). RT significantly increased the mean level of sPD-L1 (P < 0.001). Further analysis showed that the level of sPD-L1 in IDH-1 mutation patients was higher than that in wild-type patients. Furthermore, an analysis of glioma murine model indicated that anti-PD-L1 antibody combine with RT can be a potentially powerful cancer therapy. Conclusion: This study reported that sPD-L1 might be a potential biomarker to predict the outcome in glioma patients receiving RT. The elevated level of sPD-L1 after RT suggested that the strategy of a combination of immune checkpoint inhibitors and RT might be promising for glioma patients, especially for those with IDH-1 mutations.

7.
Blood ; 2020 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-33104167

RESUMO

T-cell responses to SARS-CoV-2 have been described in recovered patients, and may be important for immunity following infection and vaccination as well as for the development of an adoptive immunotherapy for the treatment of immunocompromised individuals. In this report, we demonstrate that SARS-CoV-2-specific T-cells can be expanded from convalescent donors, and recognize immunodominant viral epitopes in conserved regions of membrane, spike, and nucleocapsid. Following in vitro expansion using a GMP-compliant methodology (designed to allow the rapid translation of this novel SARS-CoV-2 T-cell therapy to the clinic), membrane, spike, and nucleocapsid peptides elicited IFN-γ production, in 27 (59%), 12 (26%), and 10 (22%) convalescent donors (respectively), as well as in 2 of 15 unexposed controls. We identified multiple polyfunctional CD4-restricted T-cell epitopes within a highly conserved region of membrane protein, which induced polyfunctional T cell responses, which may be critical for the development of effective vaccine and T cell therapies. Hence, our study shows that SARS-CoV-2 directed T-cell immunotherapy targeting structural proteins, most importantly membrane protein, should be feasible for the prevention or early treatment of SARS-CoV-2 infection in immunocompromised patients with blood disorders or after bone marrow transplantation to achieve anti-viral control while mitigating uncontrolled inflammation.

8.
Sheng Li Xue Bao ; 72(5): 651-659, 2020 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-33106835

RESUMO

The study aims to investigate the effects of cardiac fibroblast (CF) paracrine factors on murine embryonic stem cells (ESCs). Conditioned mediums from either neonatal cardiac fibroblasts (ConM-NCF) or adult cardiac fibroblasts (ConM-ACF) were diluted by 1:50 and 1:5, respectively, to investigate whether these conditioned mediums impact murine ESCs distinctly with RT-real time PCR techniques, cell proliferation essay, ELISA and by counting percentage of beating embryoid bodies (EBs) during ESCs differentiation. The data showed that the paracrine ability of CFs changed dramatically during development, in which interleukin 6 (IL6) increased with maturation. ConM-NCF 1:50 and ConM-NCF 1:5 had opposite effects on the pluripotent markers, although they both reduced mouse ESC proliferation. ConM-ACF 1:50 promoted ESCs pluripotent markers and proliferation, while ConM-ACF 1:5 exerted negative effects. All CF-derived conditioned mediums inhibited cardiac differentiation, but with distinguishable features: ConM-NCF 1:50 slightly decreased the early cardiac differentiation without altering the maturation tendency or cardiac specific markers in EBs at differentiation of day 17; ConM-ACF 1:50 had more significant inhibitory effects on early cardiac differentiation than ConM-NCF 1:50 and impeded cardiac maturation with upregulation of cardiac specific markers. In addition, IL6 neutralization antibody attenuated positive effect of ConM-ACF 1:50 on ESCs proliferation, but had no effects on ConM-NCF 1:50. Long-term IL6 neutralization reduced the percentage of beating EBs at early developmental stage, but did not alter the late cardiac differentiation. Taken together, both the quality and quantity of factors and cytokines secreted by CFs are critical for the ESC fate. IL6 could be a favorable cytokine for ESC pluripotency and the early cardiac differentiation.


Assuntos
Células-Tronco Embrionárias , Células-Tronco Embrionárias Murinas , Animais , Fibroblastos , Coração , Camundongos , Comunicação Parácrina
9.
Endocr Connect ; 9(9): 946-954, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33027757

RESUMO

Background: Obesity is associated with the development and progression of chronic kidney disease. Emerging evidence suggests that glucagon-like peptide-1 receptor agonist could reduce renal damage and albuminuria. Sirtuin 1 (SIRT1) was considered as a crucial regulator in metabolism-related kidney disease. Herein, the role of SIRT1 in liraglutide-ameliorated high-fat diet (HFD)-induced kidney injury was illustrated. Methods: Male C57BL/6 mice were fed HFD for 20 weeks to induce kidney injury that was then treated with liraglutide for 8 weeks to estimate its protective effect on the kidney. Also, the mechanism of the drug in SV40 MES 13 (SV40) mouse mesangial cells was elucidated. Results: Liraglutide treatment ameliorated HFD-induced metabolic disorders, including hyperglycemia, increasing body weight, and insulin resistance. In addition, kidney weight, urine albumin-to-creatinine, and kidney morphological changes such as vacuolated tubules, glomerulomegaly, thickened glomerular basement membrane, and tubulointerstitial fibrosis were also significantly ameliorated. Furthermore, apoptotic cells and apoptosis markers were downregulated in the kidney of liraglutide-treated mice. In addition, the expression of SIRT1 protein was upregulated, whereas thioredoxin-interacting protein (TXNIP), which serves as a mediator of oxidative stress and apoptosis in metabolism disease, was downregulated by liraglutide. In SV40 cells, the effect of liraglutide on reversing the upregulation of cleaved caspase-3 induced by high glucose (30 mM) was hampered when SIRT1 was knocked down; also, the downregulation of TXNIP by liraglutide was blocked. Conclusions: Liraglutide might have a beneficial effect on metabolism-related kidney damage by inhibiting apoptosis via activation of SIRT1 and suppression of TXNIP pathway.

10.
Zhongguo Dang Dai Er Ke Za Zhi ; 22(9): 980-983, 2020 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-32933630

RESUMO

OBJECTIVE: To study the expression level of cAMP response element-binding protein (CREB) in children with recurrent wheezing under three years of age and its effect on the expression of the serum orosomucoid 1-like protein 3 (ORMDL3) gene. METHODS: Thirty-six children with recurrent wheezing under three years of age who visited the hospital from June 2017 to June 2019 were selected as the recurrent wheezing group. Twenty-four healthy children from physical examination were selected as the control group. The CREB expression level in peripheral blood was measured by quantitative real-time PCR. Human bronchial epithelial cells (BEAS-2B) were cultured, and dual-luciferase reporter assay and quantitative real-time PCR were used to investigate the effects of overexpression and siRNA interference of CREB on the promoter activity and mRNA expression of the ORMDL3 gene in the BEAS-2B cells. RESULTS: The expression level of CREB in the recurrent wheezing group was significantly higher than that in the control group (P<0.001). In BEAS-2B cells, overexpression of CREB significantly up-regulated the promoter activity and mRNA expression of the ORMDL3 gene (P<0.05), while siRNA interference of CREB significantly reduced the promoter activity and mRNA expression of the ORMDL3 gene (P<0.05). CONCLUSIONS: The expression of CREB is increased in children with recurrent wheezing, and CREB may be involved in the pathogenesis of recurrent wheezing by regulating expression of the ORMDL3 gene.


Assuntos
Proteínas de Membrana/genética , Sons Respiratórios , Pré-Escolar , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico , Células Epiteliais , Humanos , Regiões Promotoras Genéticas
11.
FEBS Open Bio ; 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32935470

RESUMO

Acute lung injury (ALI) is accompanied by overactivation of multiple pro-inflammatory factors. Cytochrome P450 1A1 (CYP1A1) has been shown to aggravate lung injury in response to hyperoxia. However, the relationship between CYP1A1 and lipopolysaccharide (LPS)-induced ALI is unknown. In this study, CYP1A1 was shown to be upregulated in mouse lung in response to LPS. Using CYP1A1-deficient (CYP1A1-/-) mice, we found that CYP1A1 knockout enhanced LPS-induced ALI, as evidenced by increased TNF-α, IL-1ß, IL-6, and nitric oxide in lung; these effects were mediated by overactivation of NF-κB and iNOS. Furthermore, we found that aspartate aminotransferase, lactate dehydrogenase, creatine kinase, and creatinine levels were elevated in serum of LPS-induced CYP1A1-/- mice. Altogether, these data provide novel insights into the involvement of CYP1A1 in LPS-induced lung injury.

12.
Endocrine ; 70(3): 517-525, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32862405

RESUMO

PURPOSE: GLP-1 receptor agonists, such as exenatide, have been proven to attenuate nonalcoholic fatty liver disease (NAFLD) in vivo and in vitro. However, the efficiency of exenatide had interindividual differences. PNPLA3 is a major susceptibility gene for NAFLD and its I148M polymorphism increases the risk of all disorders of the NAFLD spectrum. Whether this variant contributes to variability in exenatide response is still unclear. METHODS: PNPLA3 148I knockin HepG2 cells were constructed using the Cas9/sgRNA system. Oil Red O staining combined with TG quantification was used to evaluate lipid accumulation. Western blotting and qRT-qPCR were conducted, respectively, to measure the protein and mRNA expression of lipid metabolic and endoplasmic reticulum (ER) stress-related inflammatory markers. PNPLA3 I148M was genotyped in type 2 diabetics using Sanger sequencing. The exenatide-induced changes in liver fat content and other clinical parameters were compared between PNPLA3 I148M genotypes. RESULTS: Lipid deposition increased in both PNPLA3 148I/I and 148M/M HepG2 cells treated with palmitoleic acid, while cells with 148M/M had a higher TG content than those with 148I/I. Exendin-4 treatment was showed to be more significant in 148I/I cells than in 148M/M cells in terms of reducing the intrahepatic fat content, inhibiting SREBP-1c and ER stress-related inflammation, and activating AMPK-ACC lipid oxidation pathway. In patients with type 2 diabetes, 24-week treatment with exenatide improved liver fat content in patients carrying PNPLA3 148I/I better than in patients with 148M/M. CONCLUSIONS: PNPLA3 I148M might modify the anti-NAFLD response to exenatide.

13.
Artigo em Chinês | MEDLINE | ID: mdl-32842237

RESUMO

Teratoma is a germ cell tumor, which is rare behind the ear. We described a rare case of retroauricular teratoma accompanied with congenital malformation of external and middle ear and cholesteatoma of middle ear in a 13-years-old girl. Congenital microtia and ankylotia of right ear was found since childhood, suppuration occurred repeatedly behind the right ear 1 year ago. Temporal bone CT and MRI scan revealed congenital malformation of middle ear and cholesteatoma of middle ear. Cystic mass containing a tooth was found intraoperatively. The pathological results showed that it was benign cystic teratoma. It showed no evidence of recurrence on the patient during 3 months follow-up.


Assuntos
Colesteatoma , Microtia Congênita , Teratoma , Adolescente , Criança , Orelha , Feminino , Humanos , Recidiva Local de Neoplasia
14.
J Neuroinflammation ; 17(1): 230, 2020 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-32758262

RESUMO

OBJECTIVE: Cognitive deficits and microstructural brain abnormalities are well documented in HIV-positive individuals (HIV+). This study evaluated whether chronic marijuana (MJ) use contributes to additional cognitive deficits or brain microstructural abnormalities that may reflect neuroinflammation or neuronal injury in HIV+. METHOD: Using a 2 × 2 design, 44 HIV+ participants [23 minimal/no MJ users (HIV+), 21 chronic active MJ users (HIV + MJ)] were compared to 46 seronegative participants [24 minimal/no MJ users (SN) and 22 chronic MJ users (SN + MJ)] on neuropsychological performance (7 cognitive domains) and diffusion tensor imaging metrics, using an automated atlas to assess fractional anisotropy (FA), axial (AD), radial (RD), and mean (MD) diffusivities, in 18 cortical and 4 subcortical brain regions. RESULTS: Compared to SN and regardless of MJ use, the HIV+ group had lower FA and higher diffusivities in multiple white matter and subcortical structures (p < 0.001-0.050), as well as poorer cognition in Fluency (p = 0.039), Attention/Working Memory (p = 0.009), Learning (p = 0.014), and Memory (p = 0.028). Regardless of HIV serostatus, MJ users had lower AD in uncinate fasciculus (p = 0.024) but similar cognition as nonusers. HIV serostatus and MJ use showed an interactive effect on mean diffusivity in the right globus pallidus but not on cognitive function. Furthermore, lower FA in left anterior internal capsule predicted poorer Fluency across all participants and worse Attention/Working Memory in all except SN subjects, while higher diffusivities in several white matter tracts also predicted lower cognitive domain Z-scores. Lastly, MJ users with or without HIV infection showed greater than normal age-dependent FA declines in superior longitudinal fasciculus, external capsule, and globus pallidus. CONCLUSIONS: Our findings suggest that, except in the globus pallidus, chronic MJ use had no additional negative influence on brain microstructure or neurocognitive deficits in HIV+ individuals. However, lower AD in the uncinate fasciculus of MJ users suggests axonal loss in this white matter tract that connects to cannabinoid receptor rich brain regions that are involved in verbal memory and emotion. Furthermore, the greater than normal age-dependent FA declines in the white matter tracts and globus pallidus in MJ users suggest that older chronic MJ users may eventually have lesser neuronal integrity in these brain regions.

15.
J Diabetes Investig ; 2020 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-32741144

RESUMO

AIMS/INTRODUCTION: Given that mutations related to maturity-onset diabetes of the young (MODY) are rarely found in Chinese populations, we aim to characterize the mutation spectrum of MODY pedigrees. MATERIALS AND METHODS: Maturity-onset diabetes of the young candidate gene- or exome-targeted capture sequencing was carried out in 76 probands from unrelated families fulfilling the clinical diagnostic criteria for MODY. MAF <0.01 in the GnomAD or ExAC database was used to filter significant variants. Sanger sequencing was then carried out to validate findings. Function prediction by SIFT, PolyPhen-2 and PROVEAN or CADD was carried out in missense mutations. RESULTS: A total of 32 mutations in six genes were identified in 31 families, accounting for 40.79% of the potential MODY families. The MODY subtype detection rate was 18.42% for GCK, 15.79% for HNF1A, 2.63% for HNF4A, and 1.32% for KLF11, PAX4 and NEUROG3. Seven nonsense/frameshift mutations and four missense mutations with damaging prediction were newly identified novel mutations. The clinical features of MODY2, MODY3/1 and MODYX are similar to previous reports. Clinical phenotype of NEUROG3 p.Arg55Glufs*23 is characterized by hyperglycemia and mild intermittent abdominal pain. CONCLUSIONS: This study adds to the emerging pattern of MODY epidemiology that the proportion of MODY explained by known pathogenic genes is higher than that previously reported, and found NEUROG3 as a new causative gene for MODY.

16.
BMC Womens Health ; 20(1): 143, 2020 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-32646416

RESUMO

BACKGROUND: The benefit of axillary lymph node dissection (ALND) in breast cancer patients with one or two positive sentinel lymph nodes (SLNs) remains inconclusive. The purpose of this study was to identify risk factors independently associated with axillary lymph node (ALN) metastasis. METHODS: We retrospectively analyzed data from 389 Chinese breast cancer patients with one or two positive SLNs who underwent ALND. Univariate and multivariate logistic regression analyses were performed to identify ALN metastasis-associated risk factors. RESULTS: Among the 389 patients, 174 (44.7%) had ALN metastasis, while 215 (55.3%) showed no evidence of ALN metastasis. Univariate analysis revealed significant differences in age (< 60 or ≥ 60 years), human epidermal growth factor receptor-2 (Her-2) status, and the ratio of positive to total SLNs between the ALN metastasis and non-metastasis groups (P < 0.05). The multivariate analysis indicated that age, the ratio of positive to total SLNs, and occupations were significantly different between the two groups. Lastly, younger age (< 60 years), a higher ratio of positive to total SLNs, and manual labor jobs were independently associated with ALN metastasis (P < 0.05). CONCLUSIONS: The risk of ALN metastasis in breast cancer patients with one or two positive SLNs can be further increased by younger age, manual labor jobs, and a high ratio of positive to total SLNs. Our findings may also aid in identifying which patients with one or two positive SLNs may not require ALND.


Assuntos
Axila/patologia , Neoplasias da Mama/patologia , Metástase Linfática/patologia , Biópsia de Linfonodo Sentinela/métodos , Linfonodo Sentinela/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/cirurgia , China , Feminino , Humanos , Hibridização in Situ Fluorescente , Excisão de Linfonodo , Linfonodos , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Linfonodo Sentinela/cirurgia
17.
EClinicalMedicine ; 24: 100432, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32637902

RESUMO

Background: Hematopoietic stem cell transplantation (HSCT) is curative for patients with sickle cell disease (SCD). Prior to HSCT, patients with SCD commonly receive RBC transfusions with some becoming RBC or HLA alloimmunized. This alloimmunization may impact post-HSCT transfusion requirements and donor engraftment. Methods: The study population included patients with SCD transplanted on a single-center nonmyeloablative, HLA-matched sibling HSCT trial at the National Heart, Lung, and Blood Institute (NHLBI) who had a pre-HSCT sample available for HLA class I antibody testing. We evaluated transfusion requirements and engraftment outcomes comparing patients with and without pre-existing HLA and RBC antibodies. Findings: Of 36 patients studied, 10 (28%) had HLA class I antibodies and 11 (31%) had a history of RBC alloantibodies. Up to day +45 post-HSCT, patients with HLA antibodies received more platelet transfusions (median 2.5 vs 1, p = 0.042) and those with RBC alloantibodies received more RBC units (median 7 vs 4, p = 0.0059) compared to respective non-alloimmunized patients. HLA alloimmunization was not associated with neutrophil engraftment, donor chimerism, or graft rejection. However, RBC alloimmunization correlated with a decreased donor T cell chimerism at 1 year (median 24% vs 55%, p = 0.035). Interpretation: Pre-existing HLA and RBC alloantibodies are clinically significant for patients undergoing HLA-matched nonmyeloablative HSCT. Testing for both HLA and RBC antibodies is important to help estimate transfusion needs peri­HSCT. The association of lower donor T cell chimerism and pre-existing RBC alloantibodies needs further investigation. Funding: NIH Clinical Center and NHLBI Intramural Research Program (Z99 CL999999, HL006007-11) and the Thrasher Research Fund.

18.
Transfusion ; 60(11): 2597-2610, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32627205

RESUMO

BACKGROUND: The coronavirus disease 2019 (COVID-19) epidemic affected blood collection in Guangzhou, China. STUDY DESIGN AND METHODS: This paper includes three studies. The observational study reported the trends of blood collection during the epidemic in Guangzhou, China. The cross-sectional survey investigated factors influencing blood donation during the COVID-19 epidemic, and a self-administered questionnaire was given to 1584 street whole blood donors (SWBDs) who donated during the epidemic. The randomized controlled trial involved 19 491 SWBDs who donated in 2019 but did not donate during the epidemic. Trial participants were randomly assigned to two intervention groups: Group 1 completed Questionnaire 1, which contained precautionary measures in response to COVID-19 and other messages about blood donation during the epidemic; Group 2 completed Questionnaire 2, which did not include this information. A control group did not receive any questionnaire. RESULTS: As measures were implemented, the number of blood donors increased accordingly. Both first-time and repeat SWBDs perceived the same level of blood need and donated blood because it would save lives. SWBDs who completed Questionnaire 1 expressed a greater intention to donate during the epidemic. Enabling blood donors to perceive a higher level of blood need and a lower level of COVID-19 infection risk related to blood donation mobilized experienced SWBDs to donate within 3 weeks. Intention-to-treat analyses and average-treatment-effect-on-the-treated estimations confirmed that Questionnaire 1 could motivate SWBDs to actually donate blood. CONCLUSION: Various measures could ease blood shortage during the COVID-19 epidemic. Administration of Questionnaire 1 could increase blood donations during the epidemic.

19.
Bioinformatics ; 36(19): 4902-4909, 2020 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-32609318

RESUMO

MOTIVATION: MicroRNAs (miRNAs) are small non-coding RNAs that have been successfully identified to be differentially expressed in various cancers. However, some miRNAs were reported to be up-regulated in one subtype of a cancer but down-regulated in another, making overall associations between these miRNAs and the heterogeneous cancer non-linear. These non-linearly associated miRNAs, if identified, are thus informative for cancer subtyping. RESULTS: Here, we propose mirPLS, a Partial Linear Structure identifier for miRNA data that simultaneously identifies miRNAs of linear or non-linear associations with cancer status when non-linearly associated miRNAs can then be used for subsequent cancer subtyping. Simulation studies showed that mirPLS can identify both non-linearly and linearly outcome-associated miRNAs more accurately than the comparison methods. Using the identified non-linearly associated miRNAs much improves the cancer subtyping accuracy. Applications to miRNA data of three different cancer types suggest that the cancer subtypes defined by the non-linearly associated miRNAs identified by mirPLS are consistently more predictive of patient survival and more biological meaningful. AVAILABILITY AND IMPLEMENTATION: The R package mirPLS is available for downloading from https://github.com/pfruan/mirPLS. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

20.
Nat Commun ; 11(1): 2706, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32483217

RESUMO

Aldehyde is one of most synthetically versatile functional groups and can participate in numerous chemical transformations. While a variety of simple aromatic aldehydes are commercially available, those with a more complex substitution pattern are often difficult to obtain. Benzylic oxygenation of methylarenes is a highly attractive method for aldehyde synthesis as the starting materials are easy to obtain and handle. However, regioselective oxidation of functionalized methylarenes, especially those that contain heterocyclic moieties, to aromatic aldehydes remains a significant challenge. Here we show an efficient electrochemical method that achieves site-selective electrooxidation of methyl benzoheterocycles to aromatic acetals without using chemical oxidants or transition-metal catalysts. The acetals can be converted to the corresponding aldehydes through hydrolysis in one-pot or in a separate step. The synthetic utility of our method is highlighted by its application to the efficient preparation of the antihypertensive drug telmisartan.


Assuntos
Acetais/química , Aldeídos/química , Técnicas Eletroquímicas/métodos , Hidrocarbonetos Aromáticos/química , Modelos Químicos , Acetais/síntese química , Aldeídos/síntese química , Amidinas/química , Benzimidazóis/química , Catálise , Hidrocarbonetos Aromáticos/síntese química , Hidrólise , Estrutura Molecular , Oxidantes/química , Oxirredução
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