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1.
Food Chem ; 371: 131128, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-34563970

RESUMO

Lithocarpus polystachyus Rehd. known as Sweet Tea in China has attracted lots of interest for its good hypoglycemic effect and the potential as a hypoglycemic agent. Based on affinity separation-UPLC-Q-TOF-MS/MS, 54 potential α-glucosidase inhibitiors were identified and 44 were structurally determined. Out of them, 41 were identified for the first time from this plant including flavonoids, fatty acids, triterpenes, alkaloids, and coumarins. Enzyme assays revealed that flavonoids exhibited higher inhibitory activity against α-glucosidase than others with astilbin (IC50 = 6.14 µg·mL-1), morin (IC50 = 8.46 µg·mL-1), and naringenin (IC50 = 10.03 µg·mL-1) showing 2- to 4-fold higher potency than the positive control acarbose. They were proved as reversible inhibitors with mixed inhibition mechanism. Ki (Ki') values and molecular dockings strongly supported the potency order of astilbin, morin and naringenin that showed in the enzyme assays.


Assuntos
Fagaceae , Inibidores de Glicosídeo Hidrolases , Hipoglicemiantes , Extratos Vegetais , Folhas de Planta , Espectrometria de Massas em Tandem , alfa-Glucosidases
2.
Cytokine ; 149: 155721, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34628128

RESUMO

Inflammatory bowel disease (IBD) is a chronic inflammatory disease that affects the small intestine, colon, and rectum. We evaluated associations between the interleukin 10 (IL-10) rs3024505 polymorphism and IBD, ulcerative colitis (UC), and Crohn's disease (CD) by meta-analysis. All peer-reviewed manuscripts concerning the relationship between IL-10_rs3024505 and IBD identified by searing the PubMed, Cochrane Library, EMBASE, and Chinese Medical Database were examined. The association between IL-10_rs3024505 and IBD was evaluated in allele (AG), recessive (RG), dominant (DG), homozygous (HMG), and heterozygous (HTG) genetic models. Associations were also conducted on IBD subtypes, CD and UC, and ethnicity (Non-Europeans and Europeans) subgroups. The meta-analysis included 13 studies, 8552 cases (IBD patients), and 12,830 healthy controls. Subgroup analysis of IBD (UC and CD) revealed heterogeneity in AG, DG, and HTG but no heterogeneity in RG or HMG. Moreover, AG, DG, and HTG did not show publication bias in IBD, CD, or UC, but RG and HMG exhibited publication bias. No heterogeneity and no publication bias were found among the five genetic models by a subgroup analysis of Non-Europeans and European ethnicities. The minor allele(T) of rs3024505 was significantly related to IBD: 1.37 (1.30-1.45) for AG, 2.06 (1.74-2.45) for RG, 1.39 (1.27-1.52) for DG, 2.25 (1.89-2.67) for HMG, and 1.32 (1.23-1.40) for HTG (all P < 0.00001). In the subgroup analysis of ethnicity, there was a significant effect of rs3024505 on IBD in Europeans but not non-Europeans: 1.38 (1.31-1.46) for AG, 2.07 (1.73-2.48) for RG, 1.39 (1.31-1.49) for DG, 2.26 (1.89-2.71) for HMG, and 1.33 (1.24-1.42) for HTG in Europeans (all P < 0.00001). Sensitivity analysis showed no dominant study in Europeans, but one study had a dominant impact in Non-Europeans. In conclusion, IL-10_rs3024505 polymorphism confers susceptibility to CD and UC in Europeans, but its impact should have conducted more studies in Non-Europeans.

3.
Artigo em Inglês | MEDLINE | ID: mdl-34599740

RESUMO

Microbiota of lower female reproductive tract is special in its microorganism composition with Lactobacillus as the predominant bacteria. A few of Lactobacillus species have been identified to benefit the inhibition of inflammatory and malignant diseases. Lacticaseibacillus casei LH23 is a strain isolated from traditional fermented food and had been demonstrate to ameliorate DSS-induced colitis in mice. In the present study, effects of Lacticaseibacillus casei LH23 on cervical cancer cells were investigated. Supernatants of lysates and heat-inactivated Lacticaseibacillus casei LH23 were found to inhibit the expression of human papillomavirus genes E6/E7 which is the main causative factor of cervical cancer. With MTT, EdU staining, and TUNEL staining assays, Lacticaseibacillus casei LH23 was shown to suppress the proliferation and induced the apoptosis of cervical cancer cells. Additionally, with wound-healing and Western-blot assays, Lacticaseibacillus casei LH23 was shown to slowdown the migration of cervical cancer cells and altered the expression of metastasis-related genes. These results demonstrated the anti-cervical cancer potential of Lacticaseibacillus casei LH23.

4.
Front Nutr ; 8: 739676, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34692750

RESUMO

This study investigated the effects of different levels of methionine (Met) in a low protein diet on the production performance, reproductive system, metabolism, and gut microbial composition of laying hens to reveal the underlying molecular mechanism of Met in a low protein diet on the host metabolism and gut microbial composition and function of hens. A total of 360 healthy 38-week-old Peking Pink laying hens with similar body conditions and egg production (EP) were randomly divided into four groups with nine replicates per treatment and 10 hens per replicate. The hens in each treatment group were fed low protein diets containing different levels of Met (0.25, 0.31, 0.38, and 0.47%, respectively) for 12 weeks. Feed and water were provided ad libitum throughout the trial period. The results showed that, compared with the 0.25% Met group, the final body weight (FBW), average daily gain (ADG), EP, egg weight (EW), and average daily feed intake (ADFI) in the other groups were significantly increased and feed egg ratio (FER) was decreased. Meanwhile, the EW and yield of abdominal fat (AFY) in the 0.47% Met group were higher than those in other groups. The triglyceride (TG), estradiol (E2), total protein (TP), albumin (ALB), and immunoglobulin A (IgA) in the 0.38 and 0.47% Met groups were higher than those in other groups. In addition, 16S rRNA gene sequencing revealed that there was no difference in the Sobs index, ACE index, and Shannon index among all groups. However, it is worth noting that feeding low protein diets with Met changed the gut microbial composition (e.g., the supplementation of Met increased the level of Lactobacillus and decreased the proportion of Faecalibacterium). Also, our results showed that the changes in gut microbial composition induced by the diets with different levels of Met were closely related to the changes of key parameters: ADFI, EW, FBW, TG, EM, EP, ADG, FER, and uric acid (UA). Our results highlight the role of adding an appropriate amount of Met to the low protein diet in laying hens, which could improve the gut microbial composition, production performance, reproductive system, and nutrient metabolism of laying hens. In conclusion, this study suggested that when the Met level was 0.38%, the production performance of the laying hens was pretty good.

5.
Int J Immunopathol Pharmacol ; 35: 20587384211039391, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34595959

RESUMO

INTRODUCTION: Cell-mediated autoimmunity, especially the autoreactivity of T cells, is known to underlie the initiation of anti-glomerular basement membrane disease. However, the T lymphocyte subsets that determine the disease activity, renal fibrosis, and prognosis of anti-GBM disease have not been clearly elucidated. METHODS: The T lymphocyte subsets (CD4+ and CD8+) were examined on peripheral blood and renal biopsy tissues from 65 patients with biopsy proven anti-GBM disease. Patients were divided into the high ratio group and low ratio group according to the cutoff values in the receiver operating characteristic curve analysis. The correlations of T lymphocyte subsets with clinical, pathological data, and renal outcome were analyzed. RESULTS: By the end of follow-up, 45 patients (69.2%) developed end-stage renal disease (ESRD). In peripheral blood, the CD4+/CD8+ ratio showed a predictive ability with a sensitivity and specificity of 91.3% and 52.9%, respectively, which gave rise to a cutoff value of 0.89. There was a significant difference in the activity index between these two groups (3.91 ± 1.38 vs. 2.89 ± 1.13, p = 0.007). In the renal tissues, the CD4+/CD8+ ratio had the optimal cutoff point of 0.82 with a sensitivity of 57.8% and specificity of 85%. The renal activity index was higher for the renal tissues with high CD4+/CD8+ ratios than that of tissues with low CD4+/CD8+ ratios (4.32 ± 1.55 vs. 3.37 ± 1.41, p = 0.016). Peripheral blood CD4+/CD8+ ratios of ≥0.89 or renal tissue CD4+/CD8+ ratios of < 0.82 positively correlated with poor renal prognosis in patients with anti-GBM nephritis. CONCLUSIONS: The CD4+/CD8+ ratio was associated with renal activity index both in peripheral blood and renal tissue and predicts the renal prognosis of patients with anti-GBM nephritis.

6.
ChemMedChem ; 2021 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-34687265

RESUMO

Thirty-eight disulfides containing N-arylacetamide were designed and synthesized in an effort to develop novel urease inhibitors. Biological evaluation revealed that some of the synthetic compounds exhibited strong inhibitory potency against both cell-free urease and urease in intact cell with low cytotoxicity to mammalian cells even at concentration up to 250 µM. Of note, 2,2'-dithiobis(N-(2-fluorophenyl)acetamide) (d7), 2,2'-dithiobis(N-(3,5-difluorophenyl)acetamide) (d24), and 2,2'-dithiobis(N-(3-fluorophenyl)acetamide) (d8) were here identified as the most active inhibitors with IC50 of 0.074, 0.44, and 0.81 µM, showing 32- to 355-fold higher potency than the positive control acetohydroxamic acid. These disulfides were confirmed to bind urease without covalent modification of the cysteine residue and to inhibit urease reversibly with a mixed inhibition mechanism. They also showed very good anti-Helicobacter pylori activities with d8 showing a comparable potency to the clinical used drug amoxicillin. The impressive in vitro biological profile indicated their immense potential as therapeutic agents to tackle H. pylori caused infections.

7.
Biosens Bioelectron ; 194: 113600, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34481242

RESUMO

A sensitive electrogenerated chemiluminescence (ECL) biosensor for glucose was developed based on in situ growth of TiO2 nanowires on Ti3C2 MXenes (TiO2-Ti3C2) as the nanoplatform. Via tuning the alkaline oxidation time, different amount of TiO2 nanowires can be found on MXenes. An ECL biosensor for glucose was constructed by covalent immobilization of glucose oxidase (GODx) on the glycine functional TiO2-Ti3C2 surface, with the ECL signal depending on the in-situ formation of H2O2 via the specifically catalysis of glucose by GODx, resulting in the apparent increase of ECL signal. The TiO2-Ti3C2 can also act as the catalyst for the oxidation of H2O2 into O2 to enhance the ECL of luminol. Based on this strategy, a highly sensitive ECL biosensor for glucose was obtained in wide concentration range of 20 nM-12 mM with a low detection limit of 1.2 nM (S/N = 3). The synergistic effects of large surface area, excellent conductivity, and high catalytic activity of the TiO2-Ti3C2 make the sensor highly sensitive toward glucose; the specific enzyme catalysis reaction promises excellent selectivity of the ECL sensor. The proposed biosensor has been employed to detect glucose in human serum, fruits, and sweat samples with excellent performance, providing a universal approach for glucose in various samples, which shows great prospect in clinical diagnostics and wearable sensors.


Assuntos
Técnicas Biossensoriais , Nanofios , Frutas , Glucose , Ouro , Humanos , Peróxido de Hidrogênio , Medições Luminescentes , Luminol , Suor , Titânio
8.
Am J Transl Res ; 13(8): 9437-9443, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34540063

RESUMO

OBJECTIVE: To investigate the role of amplitude integrated electroencephalography (aEEG) diagnosis in early stage of neonatal hypoxic-ischemic encephalopathy (HIE), and to evaluate the feasibility of aEEG in cerebral function monitoring in Neonatal Intensive Care Units (NICU). METHODS: 60 cases of term infants with neonatal HIE were included in the observation group, and 50 healthy term infants were enrolled as the control group. Both groups received aEEG monitoring within 6 hours after birth, and the results were analyzed. RESULTS: The correlation coefficient between the degree of asphyxia, SWC, SA and aEEG background activity was r = 0.571 (P<0.001); r = 0.512 (P<0.001) and r = 0.293 (P<0.001), respectively. The correlation coefficient between HIE degree and aEEG background activity, SWC was r = 0.742 (P<0.001) and r = 0.763 (P<0.001), respectively. The Gessell scores of the control group at 1, 3, 6, 9, and 12 months after birth were higher than those of the mild asphyxia group and the severe asphyxia group, and the mild asphyxia group showed higher Gessell scores than the severe asphyxia group (P<0.001). The predicted ROC curve of aEEG monitoring on the occurrence of neonatal HIE showed the area under the curve (AUC) = 0.6354, Std. Error = 0.05668 (95% CI: 0.5243-0.7465, P = 0.0209). CONCLUSION: aEEG had obvious diagnostic value in brain injury in the early stage of full-term neonates with asphyxia, and could be used to monitor the cerebral function of NICU, which is helpful for early clinical detection of brain injury of full-term neonates with asphyxia, so as to improve early diagnosis and treatment.

9.
Signal Transduct Target Ther ; 6(1): 333, 2021 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-34482361

RESUMO

Application of differentiation therapy targeting cellular plasticity for the treatment of solid malignancies has been lagging. Nasopharyngeal carcinoma (NPC) is a distinctive cancer with poor differentiation and high prevalence of Epstein-Barr virus (EBV) infection. Here, we show that the expression of EBV latent protein LMP1 induces dedifferentiated and stem-like status with high plasticity through the transcriptional inhibition of CEBPA. Mechanistically, LMP1 upregulates STAT5A and recruits HDAC1/2 to the CEBPA locus to reduce its histone acetylation. HDAC inhibition restored CEBPA expression, reversing cellular dedifferentiation and stem-like status in mouse xenograft models. These findings provide a novel mechanistic epigenetic-based insight into virus-induced cellular plasticity and propose a promising concept of differentiation therapy in solid tumor by using HDAC inhibitors to target cellular plasticity.

11.
Cell Death Dis ; 12(8): 740, 2021 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-34315855

RESUMO

Androgen receptor (AR) signaling inhibitors provide limited survival benefits to patients with prostate cancer (PCa), and worse, few feasible genomic lesions restrict targeted treatment to PCa. Thus, a better understanding of the critical dependencies of PCa may enable more feasible therapeutic approaches to the dilemma. We performed a kinome-scale CRISPR/Cas9 screen and identified cyclin-dependent kinase 12 (CDK12) as being conservatively required for PCa cell survival. Suppression of CDK12 by the covalent inhibitor THZ531 led to an obvious anti-PCa effect. Mechanistically, THZ531 downregulated AR signaling and preferentially repressed a distinct class of CDK12 inhibition-sensitive transcripts (CDK12-ISTs), including prostate lineage-specific genes, and contributed to cellular survival processes. Integration of the super-enhancer (SE) landscape and CDK12-ISTs indicated a group of potential PCa oncogenes, further conferring the sensitivity of PCa cells to CDK12 inhibition. Importantly, THZ531 strikingly synergized with multiple AR antagonists. The synergistic effect may be driven by attenuated H3K27ac signaling on AR targets and an intensive SE-associated apoptosis pathway. In conclusion, we highlight the validity of CDK12 as a druggable target in PCa. The synergy of THZ531 and AR antagonists suggests a potential combination therapy for PCa.

12.
Front Oncol ; 11: 656127, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34254039

RESUMO

Current approaches to predict central cervical lymph node metastasis (CLNM) in patients with papillary thyroid carcinoma (PTC) have failed to identify patients who would benefit from preventive treatment. Machine learning has offered the opportunity to improve accuracy by comparing the different algorithms. We assessed which machine learning algorithm can best improve CLNM prediction. This retrospective study used routine ultrasound data of 1,364 PTC patients. Six machine learning algorithms were compared to predict the possibility of CLNM. Predictive accuracy was assessed by sensitivity, specificity, positive predictive value, negative predictive value, and the area under the curve (AUC). The patients were randomly split into the training (70%), validation (15%), and test (15%) data sets. Random forest (RF) led to the best diagnostic model in the test cohort (AUC 0.731 ± 0.036, 95% confidence interval: 0.664-0.791). The diagnostic performance of the RF algorithm was most dependent on the following five top-rank features: extrathyroidal extension (27.597), age (17.275), T stage (15.058), shape (13.474), and multifocality (12.929). In conclusion, this study demonstrated promise for integrating machine learning methods into clinical decision-making processes, though these would need to be tested prospectively.

13.
Anal Chem ; 93(28): 9878-9886, 2021 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-34229430

RESUMO

Alzheimer's disease (AD) and Parkinson's disease (PD) are chronic neurodegenerative diseases with high morbidity and mortality. Homocysteine (Hcy), cysteine (Cys), and glutathione (GSH) are closely related to AD and PD. However, the dynamics of Hcy, Cys, and GSH in the brain tissues and the potential pathogenesis between Cys/Hcy/GSH with AD and PD remain unclear. Herein, a novel fluorescent probe 1 with multiple binding sites was rationally designed and exploited for the direct quantification of serum total Hcy and Cys along with superior optical properties. Importantly, differentiation and simultaneity fluorescence imaging of Cys, Hcy, and GSH dynamics were achieved in living cells, tissues, and mouse models of AD and PD with this probe, providing direct evidences for the relationship between Hcy/Cys/GSH and AD/PD for the first time. In addition, pathogenesis studies demonstrated that elevated Hcy and Cys levels are closely related to imbalanced redox homeostasis, increased amyloid aggregates, and nerve cell cytotoxicity. These findings will greatly promote the understanding of the functions of Hcy/Cys/GSH in Alzheimer's and Parkinson's diseases, demonstrating clinical promise for the early diagnosis and prevention of AD and PD.


Assuntos
Doença de Alzheimer , Doença de Parkinson , Animais , Cisteína , Corantes Fluorescentes , Glutationa , Células HeLa , Homocisteína , Humanos , Camundongos
14.
Front Pharmacol ; 12: 695957, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34305606

RESUMO

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease that causes high rates of disability and mortality worldwide because of severe progressive and irreversible symptoms. During the period of COPD initiation and progression, the immune system triggers the activation of various immune cells, including Regulatory T cells (Tregs), dendritic cells (DCs) and Th17 cells, and also the release of many different cytokines and chemokines, such as IL-17A and TGF-ß. In recent years, studies have focused on the role of IL-17A in chronic inflammation process, which was found to play a highly critical role in facilitating COPD. Specially, IL-17A and its downstream regulators are potential therapeutic targets for COPD. We mainly focused on the possibility of IL-17A signaling pathways that involved in the progression of COPD; for instance, how IL-17A promotes airway remodeling in COPD? How IL-17A facilitates neutrophil inflammation in COPD? How IL-17A induces the expression of TSLP to promote the progression of COPD? Whether the mature DCs and Tregs participate in this process and how they cooperate with IL-17A to accelerate the development of COPD? And above associated studies could benefit clinical application of therapeutic targets of the disease. Moreover, four novel efficient therapies targeting IL-17A and other molecules for COPD are also concluded, such as Bufei Yishen formula (BYF), a Traditional Chinese Medicine (TCM), and curcumin, a natural polyphenol extracted from the root of Curcuma longa.

15.
Orphanet J Rare Dis ; 16(1): 327, 2021 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-34294091

RESUMO

BACKGROUND: There are over 16.8 million rare disease patients in China, representing a large community that should not be neglected. While the public lack the awareness of their existence and difficult status quo, for one reason that they exist as a rare and special group in our society, for another reason that all sectors of the community haven't introduced and propagandized them suitably. However, as a special group with more difficulties in all aspects than normal healthy persons, they need enough care and love from us. To provide a basis for policy-makers to better understand the status quo of rare disease patients and care-givers in China and to devise some new policies to improve their quality of life, a comprehensive analysis of the status quo, unmet needs, difficulty caused by the rare disease is essential. METHODS: A questionnaire-based online study of patients and care-givers (usually family members) was performed. The questionnaire was composed of 116 questions, such as the diagnosis process, treatment access, financial burden, views on patients' organizations, and a series of standardized tests to assess the quality of their life, including the SF-36, PHQ-9, PHQ-15, GAD-7, and PSQI. To examine the influence of age, disease type, and relationship to patients on the scores in these tests, statistical analysis with a general linear model was conducted. FINDINGS: A total of 1959 patients and care-givers participated in the survey, representing 104 rare diseases, such as lysosomal storage diseases, hemophilia, and muscular dystrophy diseases. The diagnosis was delayed for 1.4 ± 3.0 years, and patients experienced 1.6 ± 3.8 misdiagnoses between 3.2 ± 2.4 hospitals. The hospitals where diagnoses were made were highly concentrated in 10 large hospitals (43.8%) and 5 big cities (42.1%), indicating a significant inequality of medical resources. The disease often led to difficulty in social life, education, and employment, as well as financial burden that was seldom covered by medical insurance. A battery of standardized tests demonstrated poor health status, depression, somatization, anxiety, and sleeping issues among both patients and care-givers (p < 0.05). Statistical analysis of the questionnaire also showed that poor health, anxiety, depression, somatization, and sleeping problems were more prevalent in patients than in care-givers, and more prevalent in more severe diseases (e.g., hemophilia, Dravet) or undiagnosed than in other diseases. INTERPRETATIONS: This study identified the lack of rare disease awareness and legislative support as the major challenge to rare diseases in China, and makes key recommendations for policy-makers, including legislating orphan drug act, raising rare disease awareness, providing sufficient and fair opportunities about education and employment, expanding the medical insurance coverage of treatments, and protecting rights in education and employment.


Assuntos
Qualidade de Vida , Doenças Raras , China , Humanos , Produção de Droga sem Interesse Comercial , Inquéritos e Questionários
16.
J Hazard Mater ; 419: 126443, 2021 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-34175704

RESUMO

Two-dimensional luminescence metal organic framework nanosheets (LMOF) named NH2-CuMOFs were synthesized using Cu (II) nodes coordinated with negatively charged 2-aminoterephthalic acid (NH2-BDC) via a bottom-up strategy, which were first used as the fluorescent probes for the detection of chromium Cr (VI). The nanosheets possess stable fluorescence with the maximum emission wavelength of 436 nm at excitation of 338 nm that can be effectively quenched by hexavalent chromium Cr (VI). The NH2-CuMOFs nanosheets show superior advantage over the linker of NH2-BDC for the excellent selectivity to Cr (Ⅵ) without the interferences of other metal ions. The mechanism investigation suggested that the sensitive detection of Cr (VI) was attributed to the chemical oxidation-reduction (redox) reaction and internal filtration effect (IFE) between Cr (VI) and NH2-CuMOFs nanosheets. Based on this mechanism, the quantitation of Cr (VI) was realized in the linear range of 0.1-20 µM with a detection limit of 18 nM. Moreover, the detection of Cr (VI) in real samples was also conducted with good recovery. This work provides an optical sensing nanoplatform for heavy metal ions based on two-dimensional LMOFs via a novel mechanism integrating chemical redox reaction and IFE, which may promise broad application prospect for two-dimensional luminescence nanosheets.


Assuntos
Estruturas Metalorgânicas , Pontos Quânticos , Cromo , Luminescência , Oxirredução
17.
J Agric Food Chem ; 69(26): 7303-7312, 2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34160203

RESUMO

Formaldehyde (HCHO) pollution is a scientific problem of general concern and has aroused wide attention. In this work, a fluorometric method for sensitive detection of formaldehyde was developed based on the oxidase-mimicking activity of MnO2 nanosheets in the presence of o-phenylenediamine (OPD). The MnO2 nanosheets were prepared by the bottom-up approach using manganese salt as the precursor, followed by the exfoliation with bovine serum albumin. The as-prepared MnO2 nanosheets displayed excellent oxidase-mimicking activity, and can be used as the nanoplatform for sensing in fluorometric analysis. OPD was used as a typical substrate because MnO2 nanosheets can catalyze the oxidation of OPD to generate yellow 2,3-diaminophenazine (DAP), which can emit bright yellow fluorescence at the wavelength of 560 nm. While in the presence of formaldehyde, the fluorescence was greatly quenched because formaldehyde can react with OPD to form Schiff bases that decreased the oxidation reaction of OPD to DAP. The main mechanism and the selectivity of the platform were studied. As a result, formaldehyde can be sensitively detected in a wide linear range of 0.8-100 µM with the detection limit as low as 6.2 × 10-8 M. The platform can be used for the detection of formaldehyde in air, beer, and various food samples with good performance. This work not only expands the application of MnO2 nanosheets in fluorescence sensing, but also provides a sensitive and selective method for the detection of formaldehyde in various samples via a new mechanism.


Assuntos
Compostos de Manganês , Oxirredutases , Catálise , Formaldeído , Óxidos
19.
J Leukoc Biol ; 2021 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-33884660

RESUMO

Class switch recombination (CSR) changes the effector functions of antibodies and is carried out by classical and alternative nonhomologous end joining (c-NHEJ and A-EJ) of repetitive switch (S) region double-strand breaks (DSBs). The master DNA damage response (DDR) kinase ataxia-telangiectasia mutated (ATM) is critical for CSR in part by suppressing S region DSB resection. However, whether another related DDR kinase ATM- and Rad3-related (ATR) plays similar role in CSR remains elusive. In this study, we investigated the requirement for ATR kinase activity on CSR in both c-NHEJ competent and deficient B cell lines with high-throughput sequencing of S-S junctions. We found that ATR kinase inhibition efficiently blocked both c-NHEJ- and A-EJ-mediated CSR without affecting germline transcription and activation-induced cytosine deaminase expression. In contrast to ATM, ATR does not suppress S region DSB resection and microhomology usage. In addition, ATR kinase inhibition did not affect Cas9-generated DSB end joining by either c-NHEJ and A-EJ. ATR kinase-inhibited stimulated B cells proliferate much slower than controls and exhibited altered cell cycle profile with increased G1 and G2/M phase cells. In summary, our data revealed a role for ATR in promoting both c-NHEJ- and A-EJ-mediated CSR through regulating cell proliferation upon damage without negatively influencing DSB end-joining features.

20.
Cancers (Basel) ; 13(7)2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33807449

RESUMO

This study investigated the epidemiological and clinical peculiarities of BCL2 and BCL6 rearrangement in patients with high grade B-cell lymphoma (HGBL) from Taiwan, compared with data from Western countries. Two hundred and eighty-two DLBCL cases from Taipei Medical University-affiliated hospitals (n = 179) and Tri-Service General Hospital (n = 103) were enrolled for this study. From the 282, 47 (16.7%) had MYC translocation; 24 of these harbored concurrent BCL2 and/or BCL6 translocation (double-hit, DH or triple-hit, TH). Twelve DH-HGBL cases had simultaneous MYC and BCL6 translocations, 8 harbored MYC and BCL2 rearrangement, while the remaining 4 patients exhibited TH. Together, 66.7% of DH/TH-HGBL patients were BCL6 rearrangement positive. Among these BCL6-rearranged DH/TH-HGBL patients, only 6 (37.5%) overexpressed MYC and BCL6 proteins simultaneously, indicating that MYC-BCL6 co-overexpression may not be plausible surrogate biomarker for screening BCL6-rearranged DH-HGBL. By the end of year 5, all patients with TH-HGBL, BCL2 DH-HGBL and all but one BCL6 DH-HGBL cases had expired or were lost to follow-up. Progression-free survival (PFS) was longer for the non-DH/TH-HGBL group compared with the DH/TH-HGBL group. While the patients with BCL2 DH-HGBL were lost to follow-up by day 800, their remaining TH-HGBL and BCL6 DH-HGBL peers exhibited very poor PFS, regardless of age strata. More so, patients with BCL6 rearrangement were 5.5-fold more likely associated with extranodal involvement compared with their BCL2-rearranged peers. Moreover, ~60.0% of the BCL6-rearranged DH-HGBL cases were non-GCB, suggesting that including screening for BCL6 rearrangement in patients with the non-GCB phenotype may aid medical decision-making and therapeutic strategy. Contrary to contemporary data from western countries, 2 in every 3 patients with DH/TH-HGBL in Taiwan harbor BCL6 rearrangement. Consistent with present findings, we recommend mandatory screening for BCL6 rearrangement in patients with aggressive HGBL in Taiwan.

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