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1.
Biomed Res Int ; 2021: 6673125, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34595239

RESUMO

Background: Pancreatic cancer (PC) is one of the most common cancers worldwide, with high mortality. The UGT1A gene family plays important roles in pharmacology and toxicology, contributing to interindividual differences in drug disposition. However, mRNA expression and prognostic value of the UGT1A gene family in PC have not been identified. Methods: Oncomine, GEPIA2, DAVID 6.8, Metascape, Kaplan-Meier plotter, cBioPortal, GeneMANIA, TRRUST v2, TIMER, and R software were used in our study. Results: The transcriptional levels of UGT1A1/3/6/8/9/10 in PC tissues were significantly higher than those in normal tissues. These results were further validated using five pairs of PC tumor tissues and adjacent nontumor tissues. A significant correlation was found between the expression of UGT1A1/6/10 and the pathological stage of PC. PC patients with lower transcriptional levels of UGT1A1/4/5/6/10 were associated with a better prognosis. The differentially expressed UGT1A gene family functions were primarily related to the glucuronidation pathway, cytokine-cytokine receptor interactions, and the ILK signaling pathway. Our data suggest that HNF1A, AHR, and CDX2 are key transcription factors for the UGT1A gene family. Furthermore, the expression levels of UGT1A1/3/8/9/10 were positively correlated with the activities of tumor-infiltrating immune cells, especially B cells. The expression levels of UGT1A6/9 were negatively correlated with macrophage infiltration levels. Conclusions: These results suggest that the UGT1A gene family could serve as a potential prognostic biomarker and target for PC. However, future studies are required to validate our findings and promote the clinical utility of the UGT1A gene family in PC.

2.
J Nucl Med ; 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34593594

RESUMO

18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) plays an important role in locating of primary tumor for patients with head and neck cancer of unknown primary (HNCUP). Nevertheless, it can be challenging to locate the primary malignancy in 18F-FDG-PET/CT scan in some cases. As 68Ga-radiolabeled fibroblast activation protein inhibitor (FAPI) PET/CT has promising results in detecting different tumor entities, our study aimed to evaluate the performance of 68Ga-FAPI-PET/CT for detecting the primary tumor in HNCUP patients with negative 18F-FDG findings. Methods: A total of eighteen patients (16 males and 2 females; median age, 55 years; range, 24-72 years) with negative 18F-FDG findings were enrolled in this study. All patients underwent 18F-FDG and 68Ga-FAPI-PET/CT within one week. Biopsy and histopathological examinations were done in the sites with positive 68Ga-FAPI-PET/CT findings. Results: 68Ga-FAPI-PET/CT detected the primary tumor in 7 out of 18 patients (38.89%). Among the 7 patients, in respect of the primary tumor sites, 1 was in nasopharynx, 2 were in palatine tonsil, 2 were in submandibular gland, and 2 were in hypopharynx. The primary tumors showed moderate to intensive uptake of FAPI (mean SUVmax, 8.79; range, 2.60-16.50) and excellent tumor-to-contralateral normal tissue ratio (mean SUVmax ratio, 4.50; range, 2.17-8.21). In lesion-based analysis, a total of 65 lymph nodes and 17 bone metastatic lesions were identified. The mean SUVmax of lymph node metastases were 9.05 ± 5.29 for FDG and 9.08 ± 4.69 for FAPI (P = 0.975); as for bone metastases, the mean SUVmax were 8.11 ± 3.00 for FDG and 6.96 ± 5.87 for FAPI, respectively (P = 0.478). The mean tumor-to-background ratio (TBR) values of lymph node and bone metastases were 10.65 ± 6.59 vs. 12.80 ± 8.11 (P = 0.100) and 9.08 ± 3.35 vs. 9.14 ± 8.40 (P = 0.976), respectively. Conclusion: We presented first evidence of diagnostic role of 68Ga-FAPI-PET/CT in HNCUP, and our study demonstrated that 68Ga-FAPI-PET/CT had the potential to improve the detection rate of primary tumor in HNCUP patients with negative FDG findings. Moreover, 68Ga-FAPI had similar performance in assessing metastases with 18F-FDG.

3.
Org Lett ; 23(19): 7342-7347, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34523342

RESUMO

A divergent reaction of isocyanides with o-bromobenzaldehydes for the synthesis of isoindolinone-derived ketenimines and lactams was disclosed. The reaction features readily available reactants, relatively mild conditions, and high yields of products. Ketenimines could be applied in further transformations for access to other functional molecules. A mechanism study showed that the palladium-migration/imine-insertion process was the key step in this reaction.

4.
Adv Sci (Weinh) ; : e2102500, 2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34473430

RESUMO

Combinations of immune checkpoint therapies show encouraging results in the treatment of many human cancers. However, the higher costs and greater side effects of such combinations compared with single-agent immunotherapies limit their further applications. In this work, a novel smart agent, KN046@19 F-ZIF-8, is developed to overcome these limitations. KN046 is a novel recombinant humanized PD-L1/CTLA-4 bispecific single-domain antibody-Fc fusion protein, which can bind to both PD-L1 and CTLA-4 effectively. ZIF-8 is a smart delivery system, which can safely and effectively deliver KN406 to a tumor. In vitro and in vivo results demonstrate that the smart agent KN046@19 F-ZIF-8 not only improves the immune response rate of the antibody drug in treatment of tumors but also reduces its toxic side effects, thereby achieving excellent antitumor efficacy. This study provides an engineering strategy for clinical applications of a more effective immunotherapy.

5.
Biomol NMR Assign ; 15(2): 461-466, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34436734

RESUMO

SERBP1 is a multifunctional mRNA-binding protein that has been shown to play a regulatory role in a number of biological processes such as thrombosis, DNA damage repair, and the cellular response to nutrient deprivation. Additionally, SERBP1 is upregulated in glioblastoma, leukemia as well as liver, prostrate and ovarian cancers where it has been implicated in metastatic disease and poor patient outcomes. SERBP1 binds target mRNA, stabilizing and regulating the post-translational expression of the transcript. Since SERBP1 lacks canonical RNA-binding motifs such as RRM domains or zinc fingers, its target recognition and binding mechanisms are not well understood. Recent reports suggest that it is capable of recognizing both RNA sequence motifs and structured domains. Here we report the production and purification of the intrinsically disordered C-terminal domain of SERBP1, the assignment of the 1H, 13C, 15N backbone resonances of the protein by solution-state NMR, and secondary structure predictions. We show that the protein is not entirely disordered and identify an α-helix that was stable under the experimental conditions. This work is the first step toward understanding the structural basis underpinning the molecular mechanisms of SERBP1 functions, particularly interactions with mRNA targets.

6.
Org Lett ; 2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34382812

RESUMO

A Co-catalyzed cyclization reaction of isocyanides, azides, and amines to access quinazoline derivatives was described. This protocol features a high atom economy, mild reaction conditions, excellent yields, and a broad substrate scope. This cascade reaction involved three or four C-N bonds and the formation of one or two rings. The quinazolin-4(H)-imines obtained are proven to be versatile intermediates for further valuable transformations. It was also found that the cobalt catalyst could be isolated from the reaction mixture and reused.

7.
Artigo em Inglês | MEDLINE | ID: mdl-34444326

RESUMO

Over the past decade, China has witnessed fast-paced technological advancements in the media industry, as well as major shifts in the health agenda portrayed in the media. Therefore, a key starting point when discussing health communication lies in whether media attention and public attention towards health issues are structurally aligned, and to what extent the news media guides public attention. Based on data mined from 73,060 sets of the Baidu Search Index and Media Index on 20 terms covering different types of cancer from 2011 to 2020, the Granger test demonstrates that, in the last decade, public attention and media attention towards cancer in China has gone through two distinct phases. During the first phase, 2011-2015, Chinese news media still held the key in transferring the salience of issues on most cancer types to the public. In the second phase, from 2016-2020, public attention towards cancer has gradually diverged from media coverage, mirroring the imbalance and mismatch between the demand of active public and the supply of cancer information from news media. This study provides an overview of the dynamic transition on cancer issues in China over a ten-year span, along with descriptive results on public and media attention towards specific cancer types.


Assuntos
Comunicação em Saúde , Neoplasias , Atenção , China/epidemiologia , Humanos , Meios de Comunicação de Massa , Neoplasias/epidemiologia
8.
Ophthalmic Epidemiol ; : 1-8, 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34429011

RESUMO

PURPOSE: To summarize the design and methodology of a trial designed to evaluate the efficacy and safety of low dose laser cycloplasty (LCP) in treating malignant glaucoma. METHODS: Prospective, multicentre, non-controlled clinical trial. Subjects were recruited from eight ophthalmic centers in China. The target sample size was 34. Patients aged >18 years with a clinical diagnosis of malignant glaucoma inadequately controlled on medical therapy or malignant glaucoma recurrence after topical cycloplegics withdrawal were enrolled. All patients underwent LCP under retrobulbar anesthesia or sub-Tenon anesthesia. LCP is a treatment adopting few laser points (1100-2000 mW energy, 2000 milliseconds duration) that cauterizes and remodels the ciliary body over two clock hour-positions, which may relieve the ciliary ring block. Follow-up is planned for a period of 12 months. The primary outcome is the resolution of malignant glaucoma which is defined as central anterior chamber deepening after LCP. CONCLUSION: The Malignant Glaucoma Treatment trial (MGTT) will be the first prospective trial providing evidence of a treatment for malignant glaucoma. It intends to provide clinicians an optional, easy and convenient treatment for malignant glaucoma patients. Detailed morphological and biometric information collected during the study period will also help provide experience for the outcomes of malignant glaucoma. TRIAL REGISTRATION NUMBER: ChiCTR1800017960.

9.
Environ Toxicol ; 2021 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-34427968

RESUMO

The promoting roles of faciogenital dysplasia 5 (FGD5) in tumor progression have been identified in various tumors, however, its roles in gastric cancer progression are still confusing. Currently, it was found that FGD5 was highly expressed in gastric cancer tissues and negatively correlated with different types of survival of gastric cancer patients via online dataset analysis. In vitro analysis of different types of gastric cancer cell lines and normal gastric epithelial cells obtained a consistent result. Then FGD5 was knocked down in gastric cancer cell lines through two independent siRNAs against FGD5 and it was identified that FGD5 knockdown suppressed the cancer stem cell (CSC)-like traits of gastric cancer cells through analyzing the expression of CSC markers, ALDH1 activity and spheroid-formation ability. Further mechanistic studies revealed that FGD5 interacted with Sox2 protein, a critical regulator of CSC progression, enhanced Sox2 protein stability and decreased its ubquitination. Additionally, FGD5 supported the CSC-like traits dependent on Sox2 expression. Taken together, this work identified a novel FGD5/Sox2 axis responsible for the CSC-like traits of gastric cancer cells.

10.
J Org Chem ; 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34463508

RESUMO

A one-step cascade reaction of tryptamine-derived isocyanides with in situ generated nitrile oxides for the synthesis of fused spiroindolines was described. The desired products could be efficiently synthesized in moderate to good yields (42-87%). The protocol features mild conditions, wide substrate scope, and high efficiency.

11.
Medicine (Baltimore) ; 100(32): e26911, 2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34397927

RESUMO

RATIONALE: With the recent advancements in molecular biology research, epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) have emerged as excellent therapies for patients with EGFR-mutant cancers. However, these patients inevitably develop cross-acquired resistance to EGFR-TKIs. Transformation to small-cell lung cancer (SCLC) is considered a rare resistance mechanism against EGFR-TKI therapy. Here, we report a case of TKI resistance due to SCLC transformation and demonstrate its mechanisms and clinical features. PATIENT CONCERNS: A 54-year-old Chinese man with a history of smoking for 40 years complained of an intermittent cough in March 2019. DIAGNOSIS: Transbronchial lung biopsy was performed on the basal segment of the left lower lobe, which confirmed lung adenocarcinoma. In January 2020, repeat biopsy was performed, and the results of immunohistochemistry (IHC) staining showed TTF-1 (+), CK7 (+), napsin A (+), syn (+), and CD56 (+), with a Ki-67 (+) index 80% of small cell carcinomas. Infiltrating adenocarcinomas and small cell carcinomas were observed. INTERVENTIONS: Icotinib (125 mg thrice daily) was administered as a first-line treatment from June 2019. We subsequently administered a chemotherapy regimen consisting of etoposide (180 mg, days 1-3) plus cisplatin (45 mg, days 1-3) every 3 weeks for 1 cycle after recurrence. As the patient could not tolerate further chemotherapy, he continued taking icotinib orally and received whole-brain radiotherapy 10 times to a total dose of 30 Gy after brain metastases. OUTCOMES: The patient relapsed after successful treatment with icotinib for 9 months. A partial response was achieved after 4 cycles of chemotherapy, and despite the brief success of chemotherapy, our patient exhibited brain metastasis and metastases of the eleventh thoracic spine and the second lumbar vertebra with pathological fracture. The patient eventually died of aggressive cancer progression. LESSONS: Our case highlights the possibility of SCLC transformation from EGFR-mutant adenocarcinoma and the importance of repeat biopsy for drug resistance. Serum neuron-specific enolase levels may also be useful for detecting early SCLC transformation.


Assuntos
Adenocarcinoma de Pulmão/genética , DNA de Neoplasias/genética , Neoplasias Pulmonares/genética , Mutação , Carcinoma de Pequenas Células do Pulmão/genética , Adenocarcinoma de Pulmão/metabolismo , Adenocarcinoma de Pulmão/patologia , Biópsia , Transformação Celular Neoplásica , Análise Mutacional de DNA , Receptores ErbB/genética , Receptores ErbB/metabolismo , Evolução Fatal , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/metabolismo , Masculino , Pessoa de Meia-Idade , Carcinoma de Pequenas Células do Pulmão/diagnóstico , Carcinoma de Pequenas Células do Pulmão/metabolismo , Tomografia Computadorizada por Raios X
12.
J Viral Hepat ; 28(10): 1413-1421, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34310810

RESUMO

In 2016, China officially proposed for the first time that infants born to HBsAg-positive mothers should be tested for HBsAg and anti-HBs 1-2 months after their third dose of HepB, also known as the post-vaccination serological testing programme. This study aimed to systematically evaluate the implementation and influencing factors of PVST to further reduce HBV infection risk in infants and improve the protective effect of HepB to the greatest extent. A prospective observational study was conducted to investigate the interruption of MTCT of hepatitis B. Univariate and multivariate analyses were applied to explore factors associated with the PVST follow-up rate among HBsAg-positive mothers and their infants. Additionally, bivariate analysis was performed on HBsAg and anti-HBs results in infants born to HBsAg-positive mothers. Here, the participation rate of PVST was 67.08% among 2120 pairs of positive mothers and infants. The HBsAg-positive rate among participants was 0.77%, whereas the anti-HBs positive rate was 96.84%, and both negative rates were 2.39%. Among infants with double negative results (34), only 15 completed three doses of HepB and PVST again, and 14 (93.33%) of which the antibody test results turned positive. Older mothers with high educational levels who reside in the local area were the most likely to PVST follow-up. The PVST programme is necessary to evaluate the HepB response status of newborns after vaccination. Moreover, revaccination for susceptible infants can effectively improve the MTCT-blocking rate of hepatitis B. Therefore, the scope of PVST projects in Zhejiang and China should be expanded.


Assuntos
Antígenos de Superfície da Hepatite B , Hepatite B , Feminino , Seguimentos , Hepatite B/prevenção & controle , Anticorpos Anti-Hepatite B , Vacinas contra Hepatite B , Humanos , Recém-Nascido , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Mães , Estudos Prospectivos , Vacinação
13.
Am J Physiol Gastrointest Liver Physiol ; 321(3): G344-G354, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34287088

RESUMO

As a major complication of hematopoietic stem cell transplantation, the incidence of hepatic sinusoidal obstruction syndrome (HSOS) is as high as 70%. Previous evidence has demonstrated that miR-511-3p was involved in HSOS, but the mechanism remains unclear. This study aims to examine the mechanism underlying miR-511-3p regulating HSOS. Monocrotaline (MCT) was used to create an HSOS rat model and to treat liver sinusoidal endothelial cells (LSECs). Hematoxylin & eosin (H&E) and Masson staining were used to detect pathological changes in liver tissue. The expression of miR-511-3p and Hedgehog pathway-related proteins was assessed by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. The effect of miR-511-3p in regulating HSOS was investigated by 3-(4,5)-dimethylthiahiazo-2)-3,5-diphenytetrazoliumromide (MTT), enzyme-linked immunosorbent assay (ELISA) assay, and flow cytometry. Finally, the interaction between miR-511-3p and patched1 (Ptch1) was determined by luciferase reporter assay. The rats showed a typical HSOS phenotype, including LSEC damage, liver injury, and fibrosis after MCT administration. miR-511-3p was upregulated in hepatic tissue of rat HSOS model and MCT-induced LSECs. miR-511-3p directly targeted Ptch1 and suppressed Ptch1 expression to activate the Hedgehog signaling pathway. Depletion of miR-511-3p showed a protective effect against MCT-induced HSOS, as evidenced by decreased HSOS pathogenesis factors, matrix metalloproteinases-2 (MMP-2), matrix metalloproteinases-9 (MMP-9), tumor necrosis factor-α (TNF-α), and interleukin 1 ß (IL-1ß), and decreased LSEC apoptosis rates. Nevertheless, knockdown of Ptch1 reversed the protective effect of miR-511-3p depletion against MCT-induced LSEC injury and apoptosis. miR-511-3p aggravates HSOS by activating the Hedgehog signaling pathway through targeting Ptch1, and miR-511-3p may develop as the potential therapy for the treatment of HSOS.NEW & NOTEWORTHY miR-511-3p is upregulated in HSOS in vivo and in vitro models. miR-511-3p activates the Hedgehog pathway by directly targeting Ptch1. Knockdown of miR-511-3p shows a protective effect against LSEC injury and apoptosis via Hedgehog signaling pathway. Inhibition of Ptch1 reserves the effect of miR-511-3p knockdown on LSEC damage and apoptosis.


Assuntos
Células Endoteliais/efeitos dos fármacos , Proteínas Hedgehog/metabolismo , MicroRNAs/genética , Receptor Patched-1/genética , Animais , Modelos Animais de Doenças , Células Endoteliais/metabolismo , Proteínas Hedgehog/farmacologia , Hepatopatia Veno-Oclusiva/metabolismo , Hepatopatia Veno-Oclusiva/patologia , Hepatócitos/metabolismo , Interleucina-1beta/metabolismo , Ratos , Transdução de Sinais/efeitos dos fármacos
14.
Environ Res ; 201: 111519, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34139224

RESUMO

An effective as well as eco-friendly photodegradation methods by atoxic and easily reusable photocatalysts are essential for wastewater treatment. Silver phosphate (Ag3PO4) specifically in tetrahedral shape is one of the superior catalysts under visible light but its photocorrosion, poor electron transfer ability and low surface adsorption properties limits its applications. Combination of Ag3PO4 and nitrogen doped reduced graphene oxide (NrGO) having higher in surface area, ample functional groups and hetero atom doping is expected to get over the problem. Further addition of a spinel ferrite (CuFe2O4) could enhance the visible light response activity and helps in easy separation of catalyst for reuse. Given the merits of Ag3PO4, NrGO and CuFe2O4 we rationally integrated a novel magnetically separable stable Ag3PO4/NrGO/CuFe2O4 photocatalyst for efficient detoxification of 2,4-dichlorophenol (2,4-DCP). About 95.3% degradation efficiency was achieved by Ag3PO4/NrGO/CuFe2O4 (k = 0.01978 min-1) which was ~2.6 times higher than pure Ag3PO4 (k = 0.00747 min-1) in 60 min of visible light irradiation. The Ag3PO4/NrGO/CuFe2O4 heterojunction was able to separate and recycle easily using an external magnetic field due to its strong magnetism, and after 5 recycles it showed 88.6% of degradation efficiency revealed its higher stability and recyclability. The photocatalytic mechanism of Ag3PO4/NrGO/CuFe2O4 was explained by heterojunction energy-band theory. In addition, the plausible intermediate products of 2,4-dichlorophenol were analyzed by ESI/LC-MS and proposed the pathway. Moreover, the phytotoxicity was also studied on V. radiata in which GI (germination index) was found to be 11.97% before degradation, while 80.31% of GI was observed in 60 min of degradation which revealed that more significant reduction in toxicity was attained on this photodegradation.


Assuntos
Clorofenóis , Grafite , Catálise , Fotólise
15.
Nat Commun ; 12(1): 3520, 2021 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-34112784

RESUMO

The Immunodeficiency Centromeric Instability Facial Anomalies (ICF) 4 syndrome is caused by mutations in LSH/HELLS, a chromatin remodeler promoting incorporation of histone variant macroH2A. Here, we demonstrate that LSH depletion results in degradation of nascent DNA at stalled replication forks and the generation of genomic instability. The protection of stalled forks is mediated by macroH2A, whose knockdown mimics LSH depletion and whose overexpression rescues nascent DNA degradation. LSH or macroH2A deficiency leads to an impairment of RAD51 loading, a factor that prevents MRE11 and EXO1 mediated nascent DNA degradation. The defect in RAD51 loading is linked to a disbalance of BRCA1 and 53BP1 accumulation at stalled forks. This is associated with perturbed histone modifications, including abnormal H4K20 methylation that is critical for BRCA1 enrichment and 53BP1 exclusion. Altogether, our results illuminate the mechanism underlying a human syndrome and reveal a critical role of LSH mediated chromatin remodeling in genomic stability.


Assuntos
DNA Helicases/metabolismo , Replicação do DNA , Instabilidade Genômica , Histonas/metabolismo , Rad51 Recombinase/metabolismo , Animais , Proteína BRCA1/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/genética , Montagem e Desmontagem da Cromatina/genética , Sequenciamento de Cromatina por Imunoprecipitação , DNA Helicases/deficiência , DNA Helicases/genética , Enzimas Reparadoras do DNA/genética , Enzimas Reparadoras do DNA/metabolismo , Replicação do DNA/genética , Epigênese Genética , Exodesoxirribonucleases/genética , Exodesoxirribonucleases/metabolismo , Instabilidade Genômica/genética , Histonas/deficiência , Histonas/genética , Humanos , Proteína Homóloga a MRE11/genética , Proteína Homóloga a MRE11/metabolismo , Metilação , Camundongos , RNA Interferente Pequeno , Rad51 Recombinase/genética , Regulação para Cima
16.
Acta Biochim Pol ; 2021 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-34106567

RESUMO

Aerobic glycolysis is essential for cancer cell metabolism and growth. Deubiquitinase, USP28 (ubiquitin specific peptidase 28), could maintain stability of proteins involved in tumor progression. This study was performed to investigate the role of USP28 in aerobic glycolysis of colorectal cancer. Our data showed that USP28 mRNA and protein expressions were enhanced in colorectal cancer tissues and cells. Functional assays demonstrated that overexpression of USP28 promoted cell proliferation and aerobic glycolysis of colorectal cancer, while USP28 inhibition could reverse these effects. Protein expression of Forkhead Box C1 (FOXC1) was increased by USP28 over-expression, whereas knockdown of USP28 aggravated cycloheximide (CHX; protein synthesis inhibitor) stimulated decrease of FOXC1. Moreover, proteasome inhibitor, MG132, could rescue USP28 silence-induced degradation of FOXC1. Overexpression of FOXC1 counteracted the suppressive effects of USP28 interference on colorectal cancer cell viability and aerobic glycolysis. In conclusion, USP28 enhanced cell viability and aerobic glycolysis of colorectal cancer by stabilizing FOXC1, suggesting that USP28-FOXC1 might be a novel therapeutic avenue for colorectal cancer.

17.
Chemistry ; 27(45): 11627-11632, 2021 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-34046964

RESUMO

DNA computation is considered a fascinating alternative to silicon-based computers; it has evoked substantial attention and made rapid advances. Besides realizing versatile functions, implementing spatiotemporal control of logic operations, especially at the cellular level, is also of great significance to the development of DNA computation. However, developing simple and efficient methods to restrict DNA logic gates performing in live cells is still a challenge. In this work, a series of DNA logic gates was designed by taking full advantage of the diversity and programmability of the G-quadruplex (G4) structure. More importantly, by further using the high affinity and specific endocytosis of cells to aptamer G4, an INHIBIT logic gate has been realized whose operational site is precisely restricted to specific live cells. The design strategy might have great potential in the field of molecular computation and smart bio-applications.


Assuntos
Quadruplex G , Computadores Moleculares , DNA , Lógica , Oligonucleotídeos
18.
Methods Appl Fluoresc ; 9(3)2021 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-33853048

RESUMO

The emerging and development of green chemistry has once again drawn the researchers' attention to eliminating the use and generation of hazardous materials. Here we report the use of a safe and effective fixative, chlorine dioxide (ClO2), instead of traditional hazardous fixatives for the cross-linking of cellular proteins to improve immunofluorescence staining of bacteria. The concentration of ClO2needed for 100% fixation is 50µg ml-1, which is much lower than that of traditional fixatives (1000-10000µg ml-1). The ClO2mediated cross-linking can preserve the integrity of bacterial cells and prevent cell loss through lysis. Meanwhile, lysozyme can permeabilize the bacterial cells, allowing the labelled antibodies to diffuse to their intracellular target molecules. By usingE. coliO157:H7/RP4 as a gram-negative bacteria model, immunofluorescence staining assays for both intracellular protein and surface polysaccharide were carried out to investigate the effect of ClO2fixation on the staining. The results demonstrated that ClO2fixation could prevent the target antigens from cracking off the bacteria without damage on the interaction between the antibodies and antigens (either for polysaccharide or protein). As a safe and effective fixative, ClO2has potential practical applications in immunofluorescence staining and fluorescencein situhybridization for single bacteria/cell analysis.

19.
J Zhejiang Univ Sci B ; 22(4): 318-329, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33835766

RESUMO

With the number of cases of coronavirus disease-2019 (COVID-19) increasing rapidly, the World Health Organization (WHO) has recommended that patients with mild or moderate symptoms could be released from quarantine without nucleic acid retesting, and self-isolate in the community. This may pose a potential virus transmission risk. We aimed to develop a nomogram to predict the duration of viral shedding for individual COVID-19 patients. This retrospective multicentric study enrolled 135 patients as a training cohort and 102 patients as a validation cohort. Significant factors associated with the duration of viral shedding were identified by multivariate Cox modeling in the training cohort and combined to develop a nomogram to predict the probability of viral shedding at 9, 13, 17, and 21 d after admission. The nomogram was validated in the validation cohort and evaluated by concordance index (C-index), area under the curve (AUC), and calibration curve. A higher absolute lymphocyte count (P=0.001) and lymphocyte-to-monocyte ratio (P=0.013) were correlated with a shorter duration of viral shedding, while a longer activated partial thromboplastin time (P=0.007) prolonged the viral shedding duration. The C-indices of the nomogram were 0.732 (95% confidence interval (CI): 0.685‒0.777) in the training cohort and 0.703 (95% CI: 0.642‒0.764) in the validation cohort. The AUC showed a good discriminative ability (training cohort: 0.879, 0.762, 0.738, and 0.715 for 9, 13, 17, and 21 d; validation cohort: 0.855, 0.758, 0.728, and 0.706 for 9, 13, 17, and 21 d), and calibration curves were consistent between outcomes and predictions in both cohorts. A predictive nomogram for viral shedding duration based on three easily accessible factors was developed to help estimate appropriate self-isolation time for patients with mild or moderate symptoms, and to control virus transmission.


Assuntos
COVID-19/diagnóstico , Nomogramas , Eliminação de Partículas Virais , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antivirais/sangue , Área Sob a Curva , COVID-19/virologia , Feminino , Humanos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Carga Viral
20.
PLoS One ; 16(3): e0248427, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33711050

RESUMO

BACKGROUND & AIMS: Helicobacter pylori (H. pylori) infection remains high in China though the incidence of inflammatory bowel disease (IBD) has increased. Our aim was to investigate the relationship between the prevalence of H. pylori and inflammatory bowel disease. METHODS: Hospitalized IBD patients including Crohn's disease (CD) and ulcerative colitis (UC) who had tested H. pylori antibody were enrolled. Controls were chose from age- and sex- matched healthy physical examination people who had H. pylori antibody test in a 1:2 fashion (IBD patients:controls). IBD medical history was recorded. All patients were typed by the Montreal classification. Mayo Clinic score and the Harvey-Bradshaw Severity Index were used to evaluate their disease activity. Patients and controls that had H. pylori eradication therapy before were excluded. RESULTS: Two hundred and sixty IBD patients including 213 CD patients and 47 UC patients, and 520 controls were involved in this study. The prevalence of H. pylori infection in IBD patients (9.6%, 25/260) and IBD newly diagnosed patients (12.1%, 8/66), as well as CD patients (8.9%, 19/213) including CD newly diagnosed patients (10.6%, 5/47) and UC patients (12.8%, 6/47) was significantly lower than controls (29.8%, 155/520) (p = 2.796*10-10, 0.007, 5.723*10-9, 0.016, 0.014), while there was no statistically difference between UC newly diagnosed patients and the controls, and IBD patients with different disease type, disease activity and treatment history. CONCLUSIONS: H. pylori infection had a negative association with IBD, especially CD.


Assuntos
Colite Ulcerativa , Doença de Crohn , Infecções por Helicobacter , Helicobacter pylori/isolamento & purificação , Adulto , China/epidemiologia , Colite Ulcerativa/epidemiologia , Colite Ulcerativa/microbiologia , Doença de Crohn/epidemiologia , Doença de Crohn/microbiologia , Feminino , Infecções por Helicobacter/epidemiologia , Infecções por Helicobacter/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos
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