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1.
Glia ; 2021 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-33432730

RESUMO

Stellate ganglion neurons, important mediators of cardiopulmonary neurotransmission, are surrounded by satellite glial cells (SGCs), which are essential for the function, maintenance, and development of neurons. However, it remains unknown whether SGCs in adult sympathetic ganglia exhibit any functional diversity, and what role this plays in modulating neurotransmission. We performed single-cell RNA sequencing of mouse stellate ganglia (n = 8 animals), focusing on SGCs (n = 11,595 cells). SGCs were identified by high expression of glial-specific transcripts, S100b and Fabp7. Microglia and Schwann cells were identified by expression of C1qa/C1qb/C1qc and Ncmap/Drp2, respectively, and excluded from further analysis. Dimensionality reduction and clustering of SGCs revealed six distinct transcriptomic subtypes, one of which was characterized the expression of pro-inflammatory markers and excluded from further analyses. The transcriptomic profiles and corresponding biochemical pathways of the remaining subtypes were analyzed and compared with published astrocytic transcriptomes. This revealed gradual shifts of developmental and functional pathways across the subtypes, originating from an immature and pluripotent subpopulation into two mature populations of SGCs, characterized by upregulated functional pathways such as cholesterol metabolism. As SGCs aged, these functional pathways were downregulated while genes and pathways associated with cellular stress responses were upregulated. These findings were confirmed and furthered by an unbiased pseudo-time analysis, which revealed two distinct trajectories involving the five subtypes that were studied. These findings demonstrate that SGCs in mouse stellate ganglia exhibit transcriptomic heterogeneity along maturation or differentiation axes. These subpopulations and their unique biochemical properties suggest dynamic physiological adaptations that modulate neuronal function.

2.
Theranostics ; 11(3): 1473-1492, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33391546

RESUMO

Background: Collagen type VI alpha 1 (COL6A1) has been found to be dysregulated in several human malignancies. However, the role of COL6A1 in osteosarcoma (OS) progression remains largely unclear. Here, we aimed to explore the clinical significance and biological involvement of COL6A1 in the OS cell migration and invasion. Material and Methods: We used immunohistochemistry, qRT-PCR and western blot to detect the expression of COL6A1 in 181 OS patient samples. Chromatin immunoprecipitation (ChIP) and PCR were carried out to verify the regulatory interaction of p300, c-Jun and COL6A1 promoter. The invasion and migration function of COL6A1 in OS was detected in vitro and in vivo. RNA sequence was performed to detect the downstream pathway of COL6A1, and then co-immunoprecipitation (co-IP), ubiquitination assays and rescue experiments were performed to determine the regulatory effect of COL6A1 and signal transducers and activators of transcription (STAT1). Exosomes derived from OS cell lines were assessed for the ability to promote cancer progression by co-cultured assay and exosomes tracing. Results: COL6A1 was commonly upregulated in OS tissues, especially in lung metastasis tissues, which was associated with a poor prognosis. c-Jun bound p300 increased the enrichment of H3K27ac at the promoter region of the COL6A1 gene, which resulted in the upregulation of COL6A1 in OS. Overexpression of COL6A1 promoted OS cell migration and invasion via interacting with SOCS5 to suppress STAT1 expression and activation in an ubiquitination and proteasomal degradation manner. Most interestingly, we found that exosomal COL6A1 derived from OS cells convert normal fibroblasts to cancer-associated fibroblasts (CAFs) by secreting pro-inflammatory cytokines, including IL-6 and IL-8. The activated CAFs could promote OS cell invasion and migration by mediating TGF-ß/COL6A1 signaling pathway. Conclusion: Our data demonstrated that upregulation of COL6A1 activated by H3K27 acetylation promoted the cell migration and invasion by suppressing STAT1 pathway in OS cells. Moreover, COL6A1 can be packaged into OS cell-derived exosomes and activate CAFs to promote OS metastasis.

3.
Environ Int ; 146: 106260, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33221593

RESUMO

Bisphenol A (BPA) is an industrial plasticizer widely found in consumer products, and exposure to BPA during early development has been associated with the prevalence of various cardiometabolic diseases including obesity, metabolic syndrome, type 2 diabetes, and cardiovascular diseases. To elucidate the molecular perturbations underlying the connection of low-dose prenatal BPA exposure to cardiometabolic diseases, we conducted a multi-dimensional systems biology study assessing the liver transcriptome, gut microbial community, and diverse metabolic phenotypes in both male and female mouse offspring exposed to 5 µg/kg/day BPA during gestation. Prenatal exposure to low-dose BPA not only significantly affected liver genes involved in oxidative phosphorylation, PPAR signaling and fatty acid metabolism, but also affected the gut microbial composition in an age- and sex-dependent manner. Bacteria such as those belonging to the S24-7 and Lachnospiraceae families were correlated with offspring phenotypes, differentially expressed liver metabolic genes such as Acadl and Dgat1, and key drivers identified in our gene network modeling such as Malat1 and Apoa2. This multiomics study provides insight into the relationship between gut bacteria and host liver genes that could contribute to cardiometabolic disease risks upon low-dose BPA exposure.

4.
Pest Manag Sci ; 77(1): 194-201, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32652760

RESUMO

BACKGROUND: Barnyardgrass (Echinochloa spp.) is a global weed in rice fields. Quinclorac is commonly used to control barnyardgrass. However, due to persistent use, quinclorac resistance has evolved. We obtained quinclorac-susceptible (QS) and -resistant (QR1, QR2) lines from the progeny of a single resistant E. crus-pavonis for a resistance mechanism study. RESULTS: Line QR1 exhibited resistance to high quinclorac rates (up to 6400 g ha-1 ), whereas line QR2 exhibited a resistance/susceptibility segregation ratio of 3:1 at the field or lower rates (400, 100 g ha-1 ). Intriguingly, a lower level of 14 C-quinclorac metabolism and hence a higher level of 14 C-quinclorac translocation was observed in QR1 than QS plants. The basal expression levels of 1-aminocyclopropane-1-carboxylic acid (ACC) synthase (ACS) and ACC oxidase 2 (ACO2) genes did not differ significantly between the QR1 and QS lines. However, more expression of ACS and ACO genes was induced by quinclorac treatment in QS than in QR1. Basal levels of ß-cyanoalanine synthase (ß-CAS) gene expression were similar in QS and QR1 plants, but a greater level of down-regulation was detected in QS than in QR1 plants after quinclorac treatment. CONCLUSION: These results indicate QR plants are less responsive to quinclorac than QS plants in terms of up-regulating quinclorac metabolism and ethylene synthesis. Resistance in this E. crus-pavonis line is likely controlled by a single major gene, involving possibly an alteration in auxin signal perception/transduction to the ethylene biosynthesis pathway. The ß-CAS is unlikely to play a major role in quinclorac resistance in this particular population.


Assuntos
Echinochloa , Herbicidas , Oryza , China , Echinochloa/genética , Resistência a Herbicidas/genética , Herbicidas/farmacologia , Oryza/genética , Quinolinas
5.
J Ethnopharmacol ; 268: 113660, 2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33276058

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Shuang-Huang-Lian preparation has captured wide attention since its clinical applications for the successful treatment of upper respiratory tract infection. However, its functional basis under actual therapeutic dose in vivo was still unrevealed. AIM OF THE STUDY: This study aimed to reveal the anti-flu substances and mechanism of Shuang-Huang-Lian water extract (SHL) on H1N1 infected mouse model by a strategy based on serum pharmaco-chemistry under actual therapeutic dose and network pharmacology. MATERIALS AND METHODS: H1N1 infected mouse model was employed for evaluation of the anti-flu effects of SHL. A simultaneous quantification method was developed by UPLC-TQ-XS MS coupled switch-ions mode and applied to characterize the pharmacokinetics of the multiple components of SHL under actual therapeutic dose. The potential active ingredients were screened out based on their pharmacokinetic parameters. And then, a compound mixture of these active candidates was re-evaluated for the anti-flu activity on H1N1 infected mouse model. Furthermore, the anti-flu mechanism of SHL was also predicted by network pharmacology coupled with the experimental result. RESULTS: SHL significantly increased the survival rate and prolonged survival days on H1N1 infected mice at a dosage of 20 g crude drug/kg/day by reversing the increased lung index, down-regulating the inflammatory cytokines (TNF-α, IL-1ß, IL-6) and inhibiting the release of IFN-ß in bronchoalveolar lavage fluids (BALF). Concomitantly, the pharmacokinetic parameters of fourteen quantified and twenty-one semi-quantified constituents of SHL were characterized. And then, five compounds (baicalin, sweroside, chlorogenic acid, forsythoside A and phillyrin), which displayed satisfactory pharmacokinetic features, were considered as potential active ingredients. Thus, a mixture of these five ingredients was administered to H1N1-infected mice at a dose of 4.24 mg/kg/day. As a result, the therapeutical effects of the mixture were similar to SHL in terms of survival rate, lung index and the release of cytokines (TNF-α, IL-1ß and IL-6) in BALF. Moreover, network pharmacology analysis indicated that the TNF-signal pathways might play a role in the anti-flu mechanism of SHL. CONCLUSIONS: A mixture of five compounds (baicalin, sweroside, chlorogenic acid, forsythoside A and phillyrin) were the anti-flu substances of SHL. The strategy based on serum pharmaco-chemistry under actual therapeutic dose provided a new sight on exploring in vivo effective substances of TCM.

7.
Nutrients ; 12(11)2020 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-33266410

RESUMO

Polyamines (including putrescine, spermidine, and spermine) are small, cationic molecules that are necessary for cell proliferation and differentiation. Few studies have examined the association of dietary polyamines intake with colorectal cancer risk. The aim of this study was to evaluate total polyamines, putrescine, spermidine, and spermine intake in relation to colorectal cancer risk in China. In total, 2502 colorectal cancer cases and 2538 age-(5-year interval) and sex-matched controls were recruited from July 2010 to April 2019. Odds ratios (ORs) and 95% confidence intervals (CI) were calculated by multivariable unconditional logistic regression after adjustment for various potential confounding factors. Higher intake of total polyamine, putrescine and spermidine was significantly associated with reduced risk of colorectal cancer. The adjusted ORs for the highest compared with the lowest quartile of intake were 0.60 (95% CI 0.50, 0.72; Ptrend < 0.001) for total polyamines, 0.35 (95% CI 0.29, 0.43; Ptrend < 0.001) for putrescine and 0.79 (95% CI 0.66, 0.95; Ptrend = 0.001) for spermidine, respectively. However, higher intake of spermine was associated with increased risk of colorectal cancer, with an adjusted OR of 1.58 (95% CI 1.29, 1.93; Ptrend < 0.001). This data indicate that higher intake of total polyamines, putrescine and spermidine, as well as lower intake of spermine, is associated with a decreased risk of colorectal cancer.

8.
J Lipid Res ; 2020 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-33361285

RESUMO

Genome-wide association studies (GWAS) have implicated ~380 genetic loci for plasma lipid regulation. However, these loci only explain 17-27% of the trait variance and a comprehensive understanding of the molecular mechanisms has not been achieved. In this study, we utilized an integrative genomics approach leveraging diverse genomic data from human populations to investigate whether genetic variants associated with various plasma lipid traits, namely total cholesterol (TC), high and low density lipoprotein cholesterol (HDL and LDL), and triglycerides (TG), from GWAS were concentrated on specific parts of tissue-specific gene regulatory networks. In addition to the expected lipid metabolism pathways, gene subnetworks involved in 'interferon signaling', 'autoimmune/immune activation', 'visual transduction', and 'protein catabolism' were significantly associated with all lipid traits. Additionally, we detected trait-specific subnetworks, including cadherin-associated subnetworks for LDL, glutathione metabolism for HDL, valine, leucine and isoleucine biosynthesis for TC, and insulin signaling and complement pathways for TG. Finally, utilizing gene-gene relations revealed by tissue-specific gene regulatory networks, we detected both known (e.g. APOH, APOA4, and ABCA1) and novel (e.g. F2 in adipose tissue) key regulator genes in these lipid-associated subnetworks. Knockdown of the F2 gene (Coagulation Factor II, Thrombin) in 3T3-L1 and C3H10T1/2 adipocytes reduced gene expression of Abcb11, Apoa5, Apof, Fabp1, Lipc, and Cd36, reduced intracellular adipocyte lipid content, and increased extracellular lipid content, supporting a link between adipose thrombin and lipid regulation. Our results shed light on the complex mechanisms underlying lipid metabolism and highlight potential novel targets for lipid regulation and lipid-associated diseases.

9.
Depress Anxiety ; 2020 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-33225571

RESUMO

OBJECTIVES: Low recognition and intervention rates of emotional disorders among nonpsychiatric clinical patients are primarily attributable to poor mental health awareness of patients and a paucity of mental health care resources. This study aims to investigate the association of a resource-saving brief web-based emotional-disorder self-screening plus a health self-education program (BWBED-SS + HSE) with improved mental health awareness and service-seeking attitudes among nonpsychiatric clinical patients. METHOD: A sample of 2065 patients seeking health services in nonpsychiatric clinical settings underwent BWBED-SS + HSE using mobile terminals. Participants were defined as being at high risk of anxiety and/or depression according to the optimal cut-off point of ≥11 on the Huaxi emotional-distress index (HEI). RESULTS: The rate of participants at high risk of anxiety and/or depression was 6.63%. Following participation in the BWBED-SS + HSE, after controlling for demographics, type of hospital, and test time, the rates of participants considering themselves as having an emotional disorder and willing to seek mental health services among those at high risk of anxiety and/or depression increased from 29.93% to 47.45% (adjusted odds ratio [aOR] = 2.28, p = .002) and from 11.68% to 29.93% (aOR = 3.65, p < .001), respectively. CONCLUSIONS: The BWBED-SS + HSE were associated with improved mental health awareness and service-seeking attitudes among patients seeking nonpsychiatric clinical services in China.

10.
Int J Chron Obstruct Pulmon Dis ; 15: 2817-2825, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33177819

RESUMO

Purpose: There are few studies on osteoporosis in chronic obstructive pulmonary disease-obstructive sleep apnea overlap syndrome, and the results obtained are inconsistent. The purpose of our study is to observe the occurrence of osteoporosis and its possible mechanism in rat model co-exposed to cigarette smoke and intermittent hypoxia. Materials and Methods: The rats were randomly divided into four groups: air exposed group, cigarette smoke (CS) exposed group, 10% concentration of intermittent hypoxia exposed group, CS combined with 10% concentration of intermittent hypoxia exposed group. All animals completed lung function and lung tissue morphology assessment. The femurs were examined by microcomputer tomography (microCT). Tartrate-resistant acidic phosphatase (TRAP) staining was used to evaluate the osteoclasts. We also assessed the interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in peripheral blood. Results: There was no difference in the femoral length between each group, but the quantitative analyses of microCT showed that compared with the air exposed group, the percent bone volume (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), cortical thickness (Ct.Th) and bone mineral density (BMD) decreased, and the trabecular separation (Tb.Sp) and the proportion of trap-positive cells increased significantly in the overlapping exposed group. There were higher levels of BV/TV in the overlapping group than CS exposed group. Compared with the intermittent hypoxia exposed group, there were lower levels of Tb.Th and Ct.Th and higher levels of Tb.Sp in the overlapping exposed group. However, there was no statistical difference of trap-positive cell between the overlapping exposed group and the CS exposed single group or the intermittent hypoxia exposed group. There were higher levels of IL-6 and TNF-α in the overlapping exposed group than those in the air-exposed group. Conclusion: Bone destruction increased in the overlapping exposed rat model compared with the rat exposed to air, which may be related to the upregulation of inflammation.

11.
J Hepatol ; 2020 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-33212090

RESUMO

BACKGROUND AND AIMS: Little is known about EBV-associated intrahepatic cholangiocarcinoma (EBVaICC) due to its rarity. We aimed to comprehensively investigate the clinicopathology, tumor immune microenvironment (TIME) and genomic landscape of this entity in southern China. METHODS: We evaluated 303 ICCs using in situ hybridization for EBV, we compared clinicopathological parameters between EBVaICC and nonEBVaICC, and we analyzed EBV infection status, tumor-infiltrating lymphocytes (TILs) and genomic features of EBVaICC by immunohistochemistry, double staining, nested PCR, multiplex immunofluorescence staining, fluorescence in situ hybridization and whole exome sequencing. RESULTS: EBVaICC accounted for 6.6% of ICCs, with EBV latency type I infection and clonal EBV isolates form. Distinctive clinicopathological characteristics of EBVaICC included female predominance, younger patient predominance, solitary tumor, higher HBV infection rate, lower cirrhotic background and increased lymphoepithelioma-like (LEL) subtype proportion. EBVaICC had a significantly larger TIME component than nonEBVaICC. The LEL subtype of EBVaICC, which had a significantly increased density and proportion of CD20+ B cells and CD8+ T cells, was significantly related to longer 2-year OS and RFS than EBVaICC conventional type and nonEBVaICC. Both PD-1 and PD-L1 in TILs and PD-L1 in tumor cells were overexpressed in EBVaICC. Tumor microenvironment immune type (TMIT) I (PDL1-Tumor+/CD8-High) was significantly more common in EBVaICC than in nonEBVaICC. Mutated genes in at least three cases, including MUC4, DNAH1, GLI2, LIPE, MYH7, RP11-766F14.2 and WDR36, were uncovered. EBVaICC had different mutational pattern compared with reported liver fluke-associated cholangiocarcinoma and HBV-associated ICC. CONCLUSIONS: EBVaICC, as a subset of ICC, has unique etiological characteristics, clinicopathology and molecular genetics with a significantly larger TIME component. Most cases belong to TMIT I. Paradoxically, patients with EBVaICC could be candidates for immune checkpoint therapy.

12.
Anal Chem ; 92(23): 15573-15578, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-33166461

RESUMO

The self-assembly of gold nanoparticles (Au NPs) on a liquid phase interface is often employed as a surface-enhanced Raman scattering (SERS) platform with advantages of simple preparation, high reproducibility, and a defect-free character, but they are limited to only detect a target with Raman signals. To overcome this problem, microRNA 155 without a Raman signal can be detected by a liquid phase interfacial ratiometric SERS platform. Compared with the typical solid phase SERS platform, we propose a distinctive strategy not only owning the advantages of the liquid phase interfacial platform but also breaking the limitation of recent liquid-liquid interfacial SERS analysis. This platform presents a fabulous sensitivity with a limit of detection (LOD) of 1.10 aM for microRNA 155. By simply altering the duplex-specific nuclease (DSN) enzyme amplification, our strategy can realize detection of a variety of microRNAs, paving the way to practical applications of a liquid phase SERS platform.

13.
J Dig Dis ; 2020 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-33247545

RESUMO

OBJECTIVE: Various modalities are applied for pathological diagnosis of malignant biliary strictures (MBS), including brush cytology (BC), forceps biopsy (FB) and endoscopic ultrasound-guided fine needle aspiration (EUS-FNA). We aimed to assess the value of these modalities in a repeated tissue acquisition process for biliary strictures with initially inconclusive pathological outcomes. METHODS: Patients who were suspected of having MBS and underwent a BC in two large teaching hospitals were retrospectively included. The sensitivity, specificity, positive and negative predictive values, and accuracy of the initial and repeated BC, FB and EUS-FNA were analyzed. Their performances were compared to determine which modality was superior in repeated tissue acquisition. RESULTS: In total, 476 patients were included. The sensitivity, specificity and accuracy in diagnosing MBS for the initial BC were 30.3%, 100% and 55.0%, respectively. Altogether 39, 27 and 44 patients underwent a repeat BC, FB and EUS-FNA, respectively. The sensitivity for repeated BC, FB and EUS-FNA was 41.2%, 61.1% and 44.4%, respectively, whereas their specificity all reached 100%. When comparing diagnostic accuracy, none of the modalities was superior (74.4% vs 74.1% vs 54.5%, P = 0.173). In the repeated process, one patient who underwent BC and two underwent FB developed mild pancreatitis. CONCLUSIONS: Repeated tissue acquisition achieves a conclusive diagnosis of MBS in nearly half patients who have an initially inconclusive cytological diagnosis. None of the tissue acquisition methods is significantly superior in the repeated process.

14.
Artigo em Inglês | MEDLINE | ID: mdl-33220526

RESUMO

BACKGROUND & AIMS: Although current quality indicators of colonoscopy recommend 6 minutes as the minimum standard for withdrawal time (WT), the impact of a WT longer than 6 minutes on neoplasia detection is unclear. METHODS: A multicenter randomized controlled trial involving 1027 patients was conducted from January 2018 to July 2019. Participants were randomly divided into a 9-minute (n = 514) and 6-minute (n = 513) WT group, and a timer was used to adjust the withdrawal speed. The primary outcome was the adenoma detection rate (ADR). RESULTS: Intention-to-treat analysis showed a significantly higher ADR in the 9-minute versus 6-minute WT group (36.6% vs. 27.1%, P = .001). Prolonging WT from 6 to 9 minutes significantly increased ADR of the proximal colon (21.4% vs. 11.9%, P < .001) as well as of the less experienced colonoscopists (36.8% vs. 23.5%, P = .001). Improvements were also observed in the polyp detection rate (58.0% vs. 47.8%, P < .001), and mean number of polyps and adenomas detected per colonoscopy (1.1 vs. 0.9, P = .002; 0.5 vs. 0.4, P = .008, respectively). The higher ADRs in 9-minute WT were also confirmed by the per-protocol (PP) analysis and subgroup analyses, with an increased rate of sessile serrated lesion detection in the 9-minute WT by PP analysis (4.0% vs. 1.3%, P = .04). Multivariate logistic regression demonstrated that the 9-minute WT was independently associated with increased ADR (P = .005). CONCLUSIONS: Prolonging WT from 6 to 9 minutes significantly improved ADR, especially in the proximal colon and for less experienced colonoscopists. A 9-minute WT benchmark should be considered as one of the quality indicators of colonoscopy. ClinicalTrials.gov (identifier, NCT03399045).

15.
Mol Plant ; 13(12): 1768-1783, 2020 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-33065270

RESUMO

Trichomes are universally present in plants and their development is delicately regulated. Trichomes are responsible for pubescence, whose density is associated with some agronomic traits such as insect resistance, evapotranspiration, and yield. Almost a century ago, three dominant alleles related to pubescence density in soybean, namely Pd1 (dense pubescence), Ps (sparse pubescence), and P1 (glabrous), were identified. However, their molecular identity and genetic relationships remain unclear. In this study, through a genome-wide association study and map-based cloning, we determined the genetic basis of these three traits. The sparse-pubescence phenotype of Ps was attributed to a copy-number variation of a 25.6-kb sequence that includes a gene encoding a protein with WD40 and RING domains. The dense-pubescence phenotype of Pd1 was attributed to a T-C transition in the last exon of an HD-Zip transcription factor gene, and the glabrous phenotype of P1 was caused by a G-A transition in the first exon of a lipid transfer protein gene. Genetic and biochemical analyses revealed that Pd1 functions as a transcriptional activator that can bind the promoters of the P1 and Ps genes to induce their expression; Interestingly, Pd1 can also bind its own promoter and inhibit its gene transcription. In addition, Ps can interact with Pd1 and weaken the transcriptional activity of Pd1. Taken together, our results demonstrate that Pd1, Ps, and P1 form a complex feedback loop to regulate pubescence formation in soybean.

16.
J Cancer Res Ther ; 16(5): 1191-1195, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33004770

RESUMO

Camrelizumab is a programmed death receptor-1 inhibitor originally developed in China for the treatment of refractory lymphoma. It has also been effective in non-small-cell lung cancer patients. However, the rechallenge of camrelizumab was not reported previously. We report the rechallenge of camrelizumab therapy in two patients previously treated with microwave ablation (MWA) and camrelizumab. Although objective responses were achieved, camrelizumab therapy was discontinued because of the development of immune-related pneumonia (IRP). Treatment with camrelizumab was reinitiated after the patients recovered from IRP. The reoccurrence of more severe IRP necessitated additional corticosteroid therapy. The rechallenge of camrelizumab in patients treated with MWA plus camrelizumab regimen and who developed IRP should be cautious.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Micro-Ondas/efeitos adversos , Pneumonia/tratamento farmacológico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Ablação por Radiofrequência/efeitos adversos , Antineoplásicos Imunológicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Terapia Combinada , Feminino , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Pessoa de Meia-Idade , Metástase Neoplásica , Pneumonia/etiologia , Resultado do Tratamento
17.
Am J Obstet Gynecol ; 2020 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-33127430

RESUMO

BACKGROUND: First-trimester ultrasound scans were introduced to China for nearly 20 years. The ability of first-trimester ultrasound screening to detect different malformations was variable. A recent systematic review concluded that the use of a standardized anatomic protocol was the most crucial factor to improve the sensitivity of first-trimester ultrasound screening for anomalies. Standardized sectional scans have long been used for routine anatomy screening during the second trimester. However, during the first trimester, most of the previous studies have described the observation of anatomic structures but have not specified clearly the standard sectional views. OBJECTIVE: We aimed to determine the performance of routine first-trimester scans using a standardized anatomic protocol for detecting structural abnormalities in China. STUDY DESIGN: This was a large retrospective study involving 59,063 sequential unselected pregnancies. Scans at 11 to 13+6 weeks were performed in a single center during a 7-year span. All fetuses were examined following a predefined protocol for standardized views. RESULTS: From October 2008 to December 2015, first-trimester scans were performed in 53,349 pregnant women with available outcome. Of these, there were 1578 (3%) pregnancies that presented with at least 1 fetal structural abnormality. The detection rate for first-trimester screening was 43.1% (95% confidence interval, 40.6%-45.5%). Routine first-trimester scans detected 95.6% of abdominal wall defects, 66.3% of nervous system defects, 33.8% of limbs and skeleton malformations, 30.8% of facial abnormalities, 21.2% of urogenital abnormalities, 18.4% of thoracic and lung abnormalities, and 4.1% of gastrointestinal tract abnormalities. During the first trimester, 37.7% of cardiac defects were identified and included 57.9% of major cardiac defects and 2.6% of mild cardiac defects. A robust high detection rate for anencephaly, exencephaly, cephalocele, holoprosencephaly, exomphalos, gastroschisis, Pentalogy of Cantrell, sirenomelia, and body stalk anomaly was achieved during routine first-trimester scans. CONCLUSION: A standardized anatomic protocol is advised when performing routine first-trimester ultrasound screening. It is recommended that screening for severe structural abnormalities should be extended to the first trimester.

18.
Mol Nutr Food Res ; : e2000788, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33063454

RESUMO

SCOPE: The influence of docosahexaenoic acid (DHA) on cardiometabolic and cognitive phenotypes, and multi-omic alterations in the brain under two metabolic conditions is explored to understand context-specific nutritional effects. METHODS AND RESULTS: Rats are randomly assigned to a DHA-rich or a control chow diet while drinking water or high fructose solution, followed by profiling of metabolic and cognitive phenotypes and the transcriptome and DNA methylome of the hypothalamus and hippocampus. DHA reduces serum triglyceride and improves insulin resistance and memory exclusively in the fructose-consuming rats. In hippocampus, DHA affects genes related to synapse functions in the chow group but immune functions in the fructose group; in hypothalamus, DHA alters immune pathways in the chow group but metabolic pathways in the fructose group. Network modeling reveals context-specific regulators of DHA effects, including Klf4 and Dusp1 for chow condition and Lum, Fn1, and Col1a1 for fructose condition in hippocampus, as well as Cyr61, JunB, Ier2, and Pitx2 under chow condition and Hcar1, Cdh1, and Osr1 under fructose condition in hypothalamus. CONCLUSION: DHA exhibits differential influence on epigenetic loci, genes, pathways, and metabolic and cognitive phenotypes under different dietary contexts, supporting population stratification in DHA studies to achieve precision nutrition.

19.
J Vet Med Sci ; 2020 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-33116004

RESUMO

Duck viral enteritis (DVE) is a lethal viral disease caused by duck-enteritis-virus (DEV) via an unknown mechanism. This study explores the relationship between Chinese standard challenge strain DEV (DEV-CSC)-induced apoptosis and endoplasmic reticulum stress (ERS) in duck embryo fibroblast (DEF) cells. Here we examined changes in Ca2+ concentration, cell proliferation, apoptosis, and the differential expression of C/EBP homologous protein (CHOP), glucose regulatory protein 78 (GRP78), and activating transcription factor 6 (ATF6) in infected cells. The results revealed that DEV-CSC infection significantly decreased Ca2+ concentration, suppressed cell viability, and induced apoptosis in DEF cells. Further experiments also demonstrated that DEV-CSC infection significantly upregulates CHOP, GRP78, and ATF6 expression. In addition, we show that the addition of ethylenediaminetetraacetic acid (EDTA) reverses the induction of apoptosis and the ERS mediated inhibition of cell viability in DEF cells associated with DEV-CSC infection. Therefore, we can conclude that infection with DEV-CSC induces apoptosis and ERS reducing the viability of DEF cells via the regulation of Ca2+. These findings may provide a new target for the treatment of DVE.

20.
Nat Commun ; 11(1): 5127, 2020 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-33046716

RESUMO

Despite the importance of AKT overactivation in tumor progression, results from clinical trials of various AKT inhibitors remain suboptimal, suggesting that AKT-driven tumor metastasis needs to be further understood. Herein, based on long non-coding RNA (lncRNA) profiling induced by active AKT, we identify that VAL (Vimentin associated lncRNA, LINC01546), which is directly induced by AKT/STAT3 signaling, functions as a potent pro-metastatic molecule and is essential for active AKT-induced tumor invasion, metastasis and anoikis resistance in lung adenocarcinoma (LAD). Impressively, chemosynthetic siRNAs against VAL shows great therapeutic potential in AKT overactivation-driven metastasis. Interestingly, similar to activated AKT in LAD cells, although unable to induce epithelial-mesenchymal transition (EMT), VAL exerts potent pro-invasive and pro-metastatic effects through directly binding to Vimentin and competitively abrogating Trim16-depedent Vimentin polyubiquitination and degradation. Taken together, our study provides an interesting demonstration of a lncRNA-mediated mechanism for active AKT-driven EMT-independent LAD metastasis and indicates the great potential of targeting VAL or Vimentin stability as a therapeutic approach.


Assuntos
Adenocarcinoma de Pulmão/metabolismo , Transição Epitelial-Mesenquimal , Neoplasias Pulmonares/metabolismo , RNA Longo não Codificante/metabolismo , Proteínas com Motivo Tripartido/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Vimentina/metabolismo , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/fisiopatologia , Animais , Linhagem Celular Tumoral , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/fisiopatologia , Camundongos , Metástase Neoplásica , Proteólise , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Longo não Codificante/genética , Proteínas com Motivo Tripartido/genética , Ubiquitina-Proteína Ligases/genética , Ubiquitinação , Vimentina/genética
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