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2.
Biol Pharm Bull ; 45(4): 483-490, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35370273

RESUMO

Differentiation protocols are used for induced pluripotent stem cells (iPSCs) in in vitro disease modeling and clinical applications. Transplantation of endothelial cells (ECs) is an important treatment strategy for ischemic diseases. For example, in vitro generated ECs can be used to provide the vascular plexus to regenerate organs such as the liver. Here, we demonstrate that the E-twenty-six (ETS) transcription factor ETV2 alone can directly convert iPSCs into vascular endothelial cells (iPS-ETV2-ECs) with an efficiency of over 90% within 5 d. Although the stable overexpression of ETV2 induced the expression of multiple key factors for endothelial development, the induced ECs were less mature. Furthermore, doxycycline-inducible transient ETV2 expression could upregulate the expression of von Willebrand factor (vWF) in iPS-ETV2-ECs, leading to a mature phenotype. The findings of this study on generation of mature iPS-ETV2-ECs provide further insights into the exploration of cell reprogramming from iPSCs. Here, we provide a new protocol for differentiation of iPSCs, thus providing a new source of ECs for in vitro disease modeling and clinical applications.


Assuntos
Células Endoteliais , Células-Tronco Pluripotentes Induzidas , Diferenciação Celular , Células Endoteliais/metabolismo , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Isquemia/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
3.
J Healthc Eng ; 2022: 4674959, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35432827

RESUMO

Due to the rapid development of medical engineering, massive amounts of data are recorded and preserved by various medical instruments. Therefore, finding relationships among data and summarizing clinical manifestations are of great significance to the diagnosis, treatment, and medical research of various diseases. The key to studying the nursing diagnosis support system, particularly in the urological operating room, is to select an effective classification algorithm, which is suitable for the characteristics of urological diseases. Initially, we have analyzed characteristics of urological diseases through medical data mining. Secondly, based on the traditional data mining classification method and urological disease diagnosis research, we have introduced the urological disease experimental source dataset and analyzed characteristics of the disease. Furthermore, classification algorithm and steps were introduced such as decision tree (including ID3, C4.5), Bayesian classification, BP neural network, and association rule classification algorithms. These algorithms are used to make relevant comparative experiments on the urological disease dataset. Finally, based on the diagnosis of urological diseases, a new association classification algorithm (ACCF), which is based on frequent closed item sets, is proposed along with suitable explanation. In order to verify the operational capabilities, the proposed algorithms are implemented in C++ and compared with the classification effect of traditional association classification algorithms and data mining methods. Both theoretical analysis and experiment results show that the proposed algorithm has resolved various deficiencies of the existing data mining algorithms and equally improved the accuracy of urological disease classification and prediction.


Assuntos
Diagnóstico de Enfermagem , Urologia , Algoritmos , Teorema de Bayes , Humanos , Salas Cirúrgicas
4.
Int J Biol Macromol ; 209(Pt A): 885-894, 2022 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-35439473

RESUMO

EPS66A was derived from an unidentified Streptomyces sp. HL-66 by chemical fraction and disease-resistance assays. It was identified as a polysaccharide through a series of chemical characterization, including infrared spectrum analysis, methylation, gas chromatography-mass spectrometry, nuclear magnetic resonance, and high-performance gel permeation chromatography. To determine its effect in plant, EPS66A was applied to tobacco leaves infected with TMV, resulting in the plant with enhanced systemic resistance with a significant reduction of TMV severity. Plant defense was confirmed by early responses, including hypersensitive response (HR) indicated by programed cell death, moderate alkalization, oxidative burst, increase in nitric oxide (NO) and salicylic acid (SA). Furthermore, EPS66A induced callose deposition to form defense barriers against pathogen invasion and the expression of pathogenesis-related (PR) genes, which confirmed the second level of plant defense. Therefore, EPS66A served as a resistance inducer, which was reorganized by tobacco cells that triggered the production of signal molecules. The signals moved in long distance and systemically in plant, which coordinated the expression of defense responses. The study provided a new perspective in understanding the mechanism of EPS66A in regulating plants on environmental adaptability and provided a theoretical foundation for designing safe and sustainable pesticides.

5.
Front Genet ; 13: 861096, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35350239

RESUMO

Background: More and more studies show that long non-coding RNAs (lncRNAs) have miniature open reading frames that can be translated into short peptides. Here, we identify the long non-coding gene LINC00665 and its short peptides (CIP2A-BP) in hepatocellular carcinoma (HCC) and explore how they contribute to HCC progression. Materials and methods: First, GSE101728 data were acquired through the Gene Expression Omnibus for identification of differentially expressed genes (DEGs), and gene set enrichment analysis (GSEA) was conducted to find enriched biological pathways. Then, further bioinformatics analysis was carried out on the screened long non-coding genes, and LINC00665 expression was detected in HCC and normal liver samples. The relations between LINC00665 expression, HCC prognosis, and clinical characteristics were studied. Receiver operating characteristic (ROC) analysis was also applied to verify the LINC00665 prediction in HCC prognosis. In addition, pertinent experiments on LINC00665 and CIP2A-BP were also carried out to explore their roles in the progression of HCC. Results: As a result, we screened out 332 DEGs in total, including 130 upregulated and 202 downregulated DEGs. These DEGs were mainly enriched in posttranscriptional regulation of gene expression, RNA processing, nucleolus, and gene silencing biological pathways. In addition, we found that LINC00665 was increased in HCC samples, which substantially indicated its poor prognosis. Compared with normal tissues, LINC00665 had higher expression in the pathological stages III and IV, tumor-free groups, people no more than 60 years old, and stages T3, T4, N0, N1, and M1. ROC curve indicated that the variable INC00665 had certain accuracy in predicting overall survival (OS). Moreover, in functional experiments, LINC00665 knockdown could significantly decrease HCC cell proliferation, migration, and invasion, while overexpressed CIP2A-BP could markedly increase HCC cell proliferation, invasion, and migration. Conclusion: Our findings not only disclose a unique mechanism by which CIP2A-BP encoded by LINC00665 promotes HCC carcinogenesis but suggest that these long non-coding genes and short peptides could be used as biomarkers for HCC diagnosis and prognosis and new targets for HCC therapy.

6.
mBio ; 13(2): e0364421, 2022 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-35254135

RESUMO

Plant colonization by phytopathogens is a very complex process in which numerous factors are involved. Upon infection by phytopathogens, plants produce salicylic acid (SA) that triggers gene expression within the plant to counter the invading pathogens. The present study demonstrated that SA signal also directly acts on the quorum-sensing (QS) system of the invading pathogen Xanthomonas campestris pv. campestris to affect its virulence by inducing turnover of the diffusible signaling factor (DSF) family QS signal. First, Xanthomonas campestris pv. campestris infection induces SA biosynthesis in the cabbage host plant. SA cannot be degraded by Xanthomonas campestris pv. campestris during culturing. Exogenous addition of SA or endogenous production of SA induces DSF signal turnover during late growth phase of Xanthomonas campestris pv. campestris in XYS medium that mimics plant vascular environments. Further, the DSF turnover gene rpfB is required for SA induction of DSF turnover. However, SA does not affect the expression of rpfB and DSF biosynthesis gene rpfF at the transcriptional level. SA induction of DSF turnover only occurs under acidic conditions in XYS medium. Furthermore, addition of SA to XYS medium significantly increased both culture and cytoplasmic pH. Increased cytoplasmic pH induced DSF turnover in a rpfB-dependent manner. In vitro RpfB-dependent DSF turnover activity increased when pH increased from 6 to 8. SA exposure did not affect the RpfB-dependent DSF turnover in vitro. Finally, SA-treated Xanthomonas campestris pv. campestris strain exhibited enhanced virulence when inoculated on cabbage. These results provide new insight into the roles of SA in host plants and the molecular interactions between Xanthomonas campestris pv. campestris and cruciferous plants. IMPORTANCE SA is a phenolic acid plant hormone that plays an essential role in plant defenses against biotrophic and semibiotrophic pathogens. Substantial progress has been made in understanding the pivotal role of SA in plant immunity. However, the roles of SA in inhibiting invading plant pathogens and the associated underlying molecular mechanisms are not yet fully understood. The present study demonstrated that the SA signal directly acts on the quorum-sensing (QS) system of the invading pathogen Xanthomonas campestris pv. campestris to affect its virulence by inducing turnover of the DSF family QS signal via a pH-dependent manner. These findings provide new insight into the roles of SA and expand our understanding of the molecular interactions between pathogens and plant hosts.


Assuntos
Brassica , Xanthomonas campestris , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Concentração de Íons de Hidrogênio , Percepção de Quorum/genética , Ácido Salicílico/metabolismo , Xanthomonas campestris/genética
7.
Biosens Bioelectron ; 207: 114166, 2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35279638

RESUMO

Although immunotherapy is now well established in cancer management, not every patient responds. Existing methods for assessing tumor immunotherapy responses, such as immunohistochemistry of the immune checkpoint protein programmed death ligand-1 (PD-L1), require destructive tissue analysis; furthermore, real-time in vivo monitoring would be beneficial for assessing tumor responses. Here we establish an electrochemical biosensor which was developed based on molybdenum disulfide (MoS2) and multi-wall carbon nanotubes (MWCNTs) used to modify the electrode and PD-L1 antibody-quantum dot (QD) conjugate as a dual optical and electrochemical label. The compositions, electrochemical performance, specificity of nanocomposite and probe were characterized. Paving the way for clinical application, the prepared biosensor detects differences in PD-L1 levels in diverse tumor cell types, tumors derived from mice or cancer patients, and it is reproducible and selective in both phosphate-buffered saline and serum. This study demonstrates that electrochemical sensing is a desirable technology for the in-situ and dynamic determination of biomarkers on the cellular level of for the assessment of tumor immunotherapy.


Assuntos
Técnicas Biossensoriais , Nanotubos de Carbono , Neoplasias , Animais , Antígeno B7-H1/análise , Humanos , Proteínas de Checkpoint Imunológico , Imunoterapia/métodos , Camundongos , Neoplasias/tratamento farmacológico , Neoplasias/terapia
8.
BMC Biotechnol ; 22(1): 11, 2022 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-35307009

RESUMO

BACKGROUND: Feathers are the most abundant agricultural waste produced by poultry farms. The accumulation of a large number of feathers not only seriously pollutes the environment but also causes the waste of protein resources. The degradation of feather waste by keratinase-producing strains is currently a promising method. Therefore, screening high-producing keratinase strains from marine environment and studying the fermentation conditions, enzymatic properties and feather degradation mechanism are crucial for efficient degradation of feathers. RESULTS: A novel efficient feather-degrading bacteria, Gxun-17, isolated from the soil sample of a marine duck farm of Beibu Gulf in Guangxi, China, was identified as Bacillus tropicus. The optimum fermentation conditions were obtained by single factor and orthogonal tests as follows: feather concentration of 15 g/L, maltose concentration of 10.0 g/L, MgSO4 concentration of 0.1 g/L, initial pH of 7.0 and temperature of 32.5 °C. The strain completely degraded the feathers within 48 h, and the highest keratinase activity was 112.57 U/mL, which was 3.18-fold that obtained with the basic medium (35.37 U/mL). Detecting the keratinase activity and the content of sulphur-containing compounds in the fermentation products showed that the degradation of feathers by the strain might be a synergistic effect of the enzyme and sulphite. The keratinase showed optimal enzyme activity at pH 7.0 and temperature of 60 °C. The keratinase had the best performance on the casein substrate. When casein was used as the substrate, the Km and Vmax values were 15.24 mg/mL and 0.01 mg/(mL·min), respectively. Mg2+, Ca2+, K+, Co2+, Al3+, phenylmethylsulphonyl fluoride and isopropanol inhibited keratinase activity, which indicated that it was a serine keratinase. Conversely, the keratinase activity strongly increased with the addition of Mn2+ and ß-mercaptoethanol. CONCLUSIONS: A novel feather-degrading B. tropicus Gxun-17 was obtained from marine environment. The strain adapted the extreme conditions such as low temperature, high salt and high pressure. Thus, the keratinase had high activity, wide range of temperature and pH, salt tolerance and other characteristics, which had potential application value.


Assuntos
Caseínas , Plumas , Animais , Bacillus , Caseínas/metabolismo , Galinhas/metabolismo , China , Plumas/química , Concentração de Íons de Hidrogênio , Queratinas/análise , Queratinas/química , Queratinas/metabolismo , Peptídeo Hidrolases/metabolismo , Temperatura
9.
J Crohns Colitis ; 2022 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-35239968

RESUMO

BACKGROUND AND AIMS: The UNIFI long-term extension (LTE) study reports the efficacy and safety of subcutaneous 90 mg ustekinumab through three years of maintenance therapy. METHODS: Patients randomized to ustekinumab q12w or q8w at maintenance baseline (N=348) and randomized ustekinumab-treated patients in the LTE (N=284) were evaluated. Symptomatic remission (Mayo stool frequency=0/1, rectal bleeding=0) was assessed. Safety included all LTE patients (N=188 placebo and N=457 ustekinumab). RESULTS: Among patients randomized to the ustekinumab q12w and q8w groups at maintenance baseline, 54.1% and 56.3% achieved symptomatic remission at week 152. Overall, 20% of patients discontinued ustekinumab, 10% of biologicnaïve and 30% of biologic-exposed patients. Among patients in symptomatic remission at year 3, 94.6% and 98.0% of patients were also corticosteroid free. Corticosteroid-free symptomatic remission rates in the ustekinumab q12w and q8w groups were 51.2% and 55.1% at week 152. Remission rates were higher for biologic-naïve patients than those with a history of biologic failure. Biochemical evidence of response was demonstrated by stable, decreased CRP and fecal calprotectin measurements over 3 years.From weeks 96-156, no deaths, major adverse cardiovascular events, or tuberculosis occurred. Nasopharyngitis, ulcerative colitis and upper respiratory tract infection were most frequently reported. One ustekinumab-treated patient with a history of basal cell carcinoma (BCC) reported 2 BCC. One patient in the q8w ustekinumab group who was receiving concomitant 6-mercaptopurine experienced SAEs of neutropenic sepsis and oral herpes. CONCLUSION: Efficacy of ustekinumab in patients with ulcerative colitis was confirmed through 3 years. No new safety signals were observed.

10.
Comput Intell Neurosci ; 2022: 6493311, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35341199

RESUMO

When convolutional neural network (CNN) applications have different tasks in the source domain and target domain, but both have labels, it is easy to ignore the difference between the source domain and target domain by using the current traditional method, and the recognition effect of image features is not ideal. This paper proposes a deep migration learning method based on improved ResNet based on existing research to avoid this problem. This method extracts high-order statistical features of images by increasing the number of network layers for classification when performing model transfer learning. The ImageNet dataset is used as the source domain, and a Deep Residual Network (DRN) is used for model transfer based on homogeneous data. Firstly, the ResNet model is pretrained. Then, the last fully connected layer of the source model is modified, and the final deep model is constructed by fine-tuning the network by adding an adjustment module. The impact of content differences between datasets on recognizing transfer learning features is reduced through model transfer and deep feature extraction. The deep transfer learning methods after improving ResNet are compared through experiments. The identification algorithm is based on Support Vector Machine (SVM), the deep transfer learning method on Visual Geometry Group (VGG)-19, and the deep transfer learning method based on Inception-V3. Four experiments are performed on MNIST and CIFAR-10 datasets. By analyzing the experimental data, ResNet's improved deep transfer learning method achieves 97.98% and 90.45% accuracy on the MNIST and CIFAR-10 datasets, and 95.33% and 85.07% on the test set. The accuracy and recognition accuracy on the training and test sets have been improved to a certain extent. The combination of CNN and transfer learning can effectively alleviate the difficulty of obtaining labeled data. Therefore, the application of a CNN in transfer learning is significant.


Assuntos
Algoritmos , Redes Neurais de Computação , Máquina de Vetores de Suporte
11.
Acta Pharm Sin B ; 12(2): 787-800, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35256947

RESUMO

The bile acid-responsive G-protein-coupled receptor TGR5 is expressed in monocytes and macrophages, and plays a critical role in regulating inflammatory response. Our previous work has shown its role in promoting the progression of non-small cell lung cancer (NSCLC), yet the mechanism remains unclear. Here, using Tgr5-knockout mice, we show that TGR5 is required for M2 polarization of tumor-associated macrophages (TAMs) and suppresses antitumor immunity in NSCLC via involving TAMs-mediated CD8+ T cell suppression. Mechanistically, we demonstrate that TGR5 promotes TAMs into protumorigenic M2-like phenotypes via activating cAMP-STAT3/STAT6 signaling. Induction of cAMP production restores M2-like phenotypes in TGR5-deficient macrophages. In NSCLC tissues from human patients, the expression of TGR5 is associated with the infiltration of TAMs. The co-expression of TGR5 and high TAMs infiltration are associated with the prognosis and overall survival of NSCLC patients. Together, this study provides molecular mechanisms for the protumor function of TGR5 in NSCLC, highlighting its potential as a target for TAMs-centric immunotherapy in NSCLC.

12.
J Clin Oncol ; : JCO2101667, 2022 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-35263150

RESUMO

PURPOSE: To ascertain if preoperative short-term radiotherapy followed by chemotherapy is not inferior to a standard schedule of long-term chemoradiotherapy in patients with locally advanced rectal cancer. MATERIALS AND METHODS: Patients with distal or middle-third, clinical primary tumor stage 3-4 and/or regional lymph node-positive rectal cancer were randomly assigned (1:1) to short-term radiotherapy (25 Gy in five fractions over 1 week) followed by four cycles of chemotherapy (total neoadjuvant therapy [TNT]) or chemoradiotherapy (50 Gy in 25 fractions over 5 weeks, concurrently with capecitabine [chemoradiotherapy; CRT]). Total mesorectal excision was undertaken 6-8 weeks after preoperative treatment, with two additional cycles of CAPOX (intravenous oxaliplatin [130 mg/m2, once a day] on day 1 and capecitabine [1,000 mg/m2, twice a day] from days 1 to 14) in the TNT group and six cycles of CAPOX in the CRT group. The primary end point was 3-year disease-free survival (DFS). RESULTS: Between August 2015 and August 2018, a total of 599 patients were randomly assigned to receive TNT (n = 302) or CRT (n = 297). At a median follow-up of 35.0 months, 3-year DFS was 64.5% and 62.3% in TNT and CRT groups, respectively (hazard ratio, 0.883; one-sided 95% CI, not applicable to 1.11; P < .001 for noninferiority). There was no significant difference in metastasis-free survival or locoregional recurrence, but the TNT group had better 3-year overall survival than the CRT group (86.5% v 75.1%; P = .033). Treatment effects on DFS and overall survival were similar regardless of prognostic factors. The prevalence of acute grade III-V toxicities during preoperative treatment was 26.5% in the TNT group versus 12.6% in the CRT group (P < .001). CONCLUSION: Short-term radiotherapy with preoperative chemotherapy followed by surgery was efficacious with acceptable toxicity and could be used as an alternative to CRT for locally advanced rectal cancer.

13.
Food Chem ; 385: 132649, 2022 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-35278735

RESUMO

This work reports a sensitive and accurate multimode detection method to detect Salmonella typhimurium using inherent color, photothermal and catalytic properties of Prussian blue@gold nanoparticles (PB@Au). The inherent color of PB@Au can realize direct visual detection while the temperature increase (ΔT) of it can realize sensitive and quantitative photothermal detection. Moreover, catalytic coloration detection is applied to further amplify detection signal. The risk limit, prevention and control of Salmonella typhimurium can be more intuitively displayed through catalytic color overlap degree between PB@Au and catalytic product. The sensitivity of method is improved through photothermal and catalytic coloration detection (101 CFU·mL-1) compared with direct visual detection (102 CFU·mL-1). The multimode detection improves the accuracy of method, and exhibits good repeatability, acceptable selectivity and stability. This method is also successfully applied in real samples, displaying its good practical applicability.


Assuntos
Técnicas Biossensoriais , Nanopartículas Metálicas , Nanocompostos , Técnicas Biossensoriais/métodos , Ouro , Limite de Detecção , Salmonella typhimurium
14.
Artigo em Inglês | MEDLINE | ID: mdl-35294365

RESUMO

Band selection (BS) reduces effectively the spectral dimension of a hyperspectral image (HSI) by selecting relatively few representative bands, which allows efficient processing in subsequent tasks. Existing unsupervised BS methods based on subspace clustering are built on matrix-based models, where each band is reshaped as a vector. They encode the correlation of data only in the spectral mode (dimension) and neglect strong correlations between different modes, i.e., spatial modes and spectral mode. Another issue is that the subspace representation of bands is performed in the raw data space, where the dimension is often excessively high, resulting in a less efficient and less robust performance. To address these issues, in this article, we propose a tensor-based subspace clustering model for hyperspectral BS. Our model is developed on the well-known Tucker decomposition. The three factor matrices and a core tensor in our model encode jointly the multimode correlations of HSI, avoiding effectively to destroy the tensor structure and information loss. In addition, we propose well-motivated heterogeneous regularizations (HRs) on the factor matrices by taking into account the important local and global properties of HSI along three dimensions, which facilitates the learning of the intrinsic cluster structure of bands in the low-dimensional subspaces. Instead of learning the correlations of bands in the original domain, a common way for the matrix-based models, our model learns naturally the band correlations in a low-dimensional latent feature space, which is derived by the projections of two factor matrices associated with spatial dimensions, leading to a computationally efficient model. More importantly, the latent feature space is learned in a unified framework. We also develop an efficient algorithm to solve the resulting model. Experimental results on benchmark datasets demonstrate that our model yields improved performance compared to the state-of-the-art.

15.
Artigo em Inglês | MEDLINE | ID: mdl-35178098

RESUMO

OBJECTIVE: To explore the potential active components and corresponding target herb pairs of Radix Ginseng (Renshen) and Radix Bupleuri (Chaihu) in the treatment of nonalcoholic fatty liver disease (NAFLD) through network pharmacology and in vitro experiments. METHODS: The active components and potential targets of the herb pair of Renshen and Chaihu were screened through a network database system, and Venn analysis was performed with the obtained NAFLD targets. The intersecting targets were analysed for gene ontology (GO) functions and Kyoto Encyclopedia of Genes and Genome (KEGG) pathways, and a protein-protein interaction (PPI) network was generated. Cytoscape software was used to construct active component-target networks of the Renshen and Chaihu herb pair. Free fatty acids were added to the HepG2 cell line to create high-fat models that were treated with different concentrations of stigmasterol. The effect of stigmasterol on the lipid metabolism in HepG2 cells and PPARγ-knockdown cells was determined by oil red O staining, Nile red staining, and TG level. PPARγ and UCP-1 mRNA, and protein expression levels were detected by qRT-PCR and Western blot analyses, respectively. RESULTS: Twenty active components obtained from the Renshen and Chaihu herb pair were identified. The herb pair active component-target network showed that both Renshen and Chaihu contained stigmasterol and kaempferol as active components. The PPI network comprised 63 protein nodes. GO enrichment analysis and KEGG pathway enrichment analysis showed that the targets were mainly involved in lipid metabolism. Eight core targets were identified: AKT1, PPARG, MAPK3, TNF, TP53, SIRT1, STAT3, and PPARA. In vitro experiments demonstrated that stigmasterol reduced lipid accumulation and TG levels in HepG2 cells, and the mechanism may have been related to the activation of the PPARγ-UCP-1 signalling pathway. CONCLUSION: This study preliminarily illustrated the potential components and corresponding core targets of the Renshen and Chaihu herb pair in treating NAFLD. The effect of stigmasterol on the PPARγ-UCP-1 signalling pathway in enhancing lipid metabolism may represent one of the mechanisms of the Renshen and Chaihu herb pair in the treatment of NAFLD. The results provide new evidence and research insights to reveal the roles of Renshen and Chaihu in the management of NAFLD.

16.
J Food Sci ; 87(3): 886-894, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35142373

RESUMO

ß-Glucosidase is a key enzyme that hydrolyzes nonvolatile glycosylated precursors of aroma compounds and enhances the organoleptic quality of wines. In this study, a novel ß-glucosidase from Hanseniaspora uvarum Yun268 was localized, purified, and characterized. Results indicated that ß-glucosidase activity was mainly distributed within the cells. After purification via ammonium sulfate precipitation combined with chromatography, ß-glucosidase specific activity increased 8.36 times, and the activity recovery was 56.90%. The enzyme had a molecular mass of 74.22 kDa. It has a Michaelis constant (Km ) of 0.65 mmol/L, and a maximum velocity (Vmax ) of 5.1 nmol/min under optimum conditions; and Km of 0.94 mmol/L, and Vmax of 2.8 nmol/min under typical winemaking conditions. It exhibited the highest activity at 50°C and pH 5.0 and was stable at a temperature range of 20-80°C and pH range of 3.0-8.0. The enzyme has good tolerance to Fe3+ , especially maintaining 93.68% of its activity with 10 mmol/L of Fe3+ . Ethanol (<20%) and glucose (<150 g/L) inhibited its activity only slightly. Therefore, ß-glucosidase from H. uvarum Yun268 has excellent biochemical properties and a good application potential in winemaking. PRACTICAL APPLICATION: Winemaking is a biotechnological process in which exogenous ß-glucosidase is used to overcome the deficiency of endogenous ß-glucosidase activity in grapes. By localizing, purifying, and characterizing of ß-glucosidase from Hanseniaspora uvarum Yun268, it is expected to reveal its physical and chemical characteristics to evaluate its oenological properties in winemaking. The results may provide the basis for promoting the release of varietal aroma and improving wine sensory quality in the wine industry.


Assuntos
Hanseniaspora , Vinho , Fermentação , Odorantes/análise , Vinho/análise , beta-Glucosidase/metabolismo
17.
Signal Transduct Target Ther ; 7(1): 38, 2022 02 11.
Artigo em Inglês | MEDLINE | ID: mdl-35145057

RESUMO

Small interfering RNA (siRNA) constitutes a promising therapeutic modality supporting the potential functional cure of hepatitis B. A novel ionizable lipidoid nanoparticle (RBP131) and a state-of-the-art lyophilization technology were developed in this study, enabling to deliver siRNA targeting apolipoprotein B (APOB) into the hepatocytes with an ED50 of 0.05 mg/kg after intravenous injection. In addition, according to the requirements of Investigational New Drug (IND) application, a potent siRNA targeting hepatitis B virus (HBV) was selected and encapsulated with RBP131 to fabricate a therapeutic formulation termed RB-HBV008. Efficacy investigations in transient and transgenic mouse models revealed that the expressions of viral RNAs and antigens (HBsAg and HBeAg), as well as viral DNA, were repressed, dose-dependently and time-dependently at multilog decreasing amplitude, in both circulation and liver tissue. In contrast, entecavir (ETV), the first-line clinically-employed nucleoside analog drug, barely recused the antigen expression, although it triggered as high as 3.50 log reduction of viral DNA, in line with clinical observations. Moreover, the toxicity profiles suggested satisfactory safety outcomes with ten times the therapeutic window. Therefore, this study provides an effective nucleic acid delivery system and a promising RNAi agent for the treatment of hepatitis B.


Assuntos
Regulação Viral da Expressão Gênica/efeitos dos fármacos , Antígenos de Superfície da Hepatite B , Antígenos E da Hepatite B , Vírus da Hepatite B , Hepatite B , RNA Interferente Pequeno , Células Hep G2 , Hepatite B/tratamento farmacológico , Hepatite B/genética , Hepatite B/metabolismo , Antígenos de Superfície da Hepatite B/biossíntese , Antígenos de Superfície da Hepatite B/genética , Antígenos E da Hepatite B/biossíntese , Antígenos E da Hepatite B/genética , Vírus da Hepatite B/genética , Vírus da Hepatite B/metabolismo , Humanos , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/farmacologia
18.
Artigo em Inglês | MEDLINE | ID: mdl-35171427

RESUMO

In this study, the performance of shortcut nitrification-denitrification (SCND) at different TC and SD stress conditions (0 µg/L, 1-97 days; 100 µg/L, 98-138 days; 500 µg/L, 139-175 days) was investigated. Higher level antibiotic stress (500 µg/L) led to the serious deterioration of nitrogen removal, and denitrification was more sensitive to antibiotic stress than nitrification. The dynamics of antibiotic resistance genes (ARGs) and microbial community were revealed by quantitative real-time PCR and 16S rDNA high-throughput sequencing, respectively. Tet-genes (tetA, tetQ, tetW), sul-genes (sulI, sulII), and mobile genetic element (intI1) in activated sludge increased by 1.2 ~ 2.5 logs with long-term exposure of antibiotic stress, and sulI, tetA, tetQ, and tetW were significantly positively correlated with intI1. Long-term antibiotics stress caused the decrease of most denitrifiers, and five genera were identified as the potential host of ARGs. The key impact factors of SCND drove the dynamics of ARGs and microbial community. Except for sulII gene, DO and FA were significantly positively correlated with ARGs, while FNA, NAR, and NO2--N showed opposite effects to ARGs. Overall, maintaining relative lower DO, higher FNA, NAR, and NO2--N conditions are not only benefit to the stable operation of SCND, but may also conducive to the control of ARG dissemination. This study provides theoretical basis on the control of ARGs in the SCND process.

19.
Front Neurosci ; 16: 820106, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35185459

RESUMO

Alcohol use disorders (AUD) is characterized by persistent or intermittent alcohol cravings and compulsive drinking. The functional changes in the central nervous system (CNS) after alcohol consumption are alcohol-associated cognitive impairment and mood disorders, which are major health issues reported in AUDs. Studies have shown that transferring the intestinal microbiota from AUDs patients to germ-free animals causes learning and memory dysfunction, depression and anxiety-like behavior, indicating the vital role of intestinal microbiota in development of neuropsychiatric disorders in AUD. Intestinal flora composition of AUD patients are significantly different from normal people, suggesting that intestinal flora imbalance orchestrate the development of neuropsychiatric disorders in AUD. Studies suggests that gut microbiome links bidirectional signaling network of the enteric nervous system (ENS) to central nervous system (CNS), forming gut-microbe-brain axis (brain-gut axis). In this review, we discussed pathogenesis and possible treatment of AUD-induced cognitive deficits, anxiety, and depression disorders. Further, we described the mechanism of intestinal flora imbalance and dysfunction of hippocampus-amygdala-frontal cortex (gut-limbic circuit system dysfunction). Therefore, we postulate therapeutic interventions of gut-brain axis as novel strategies for treatment of AUD-induced neuropsychiatric disorders.

20.
Acta Biochim Pol ; 69(1): 139-145, 2022 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-35226448

RESUMO

Lung cancer, a most common clinically diagnosed malignancy grows rapidly and undergoes metastasis/diffusion to distant organs at a fast rate. In the present study gravacridondiol tetrazole (tetrazole) was synthesized and investigated for lung cancer growth inhibition potential in vitro. MTT assay and flow cytometry using propidium iodide were used to determine viability changes and DNA content distribution. Protein expression and apoptotic changes were detected by western blotting and Annexin-V/PI assays. Treatment with 12 µM tetrazole suppressed viabilities to 23% and 20% in A549 and NCI-H1819 cells, respectively. In tetrazole exposed cells, G1-phase cell count increased significantly compared to the control. Tetrazole-treatment of A549 and NCI-H1819 cells caused a prominent raise in LC3­II and p-ERK1/2 expression at 72 h. The SQSTM1/p62 level, p-mTOR and p-p70S6K expression was lowered significantly in A549 and NCI-H1819 cells on exposure to tetrazole. Exposure to U1026 alleviated tetrazole mediated LC3II/I ratio increase in A549 and NCI-H1819 cells significantly (P<0.02) compared to tetrazole treated cells. Treatment with tetrazole and 3­MA in combination led a significant (P<0.02) elevation in A549 and NCI-H1819 cell apoptotic count relative to tetrazole (12 µM) alone treated cells. Moreover, tetrazole and 3­MA combination increased cleavage of caspase­3 to a greater extent compared to tetrazole. In summary, tetrazole manifested anti-proliferative effect on lung cancer cells via autophagy over-activation and arrest of cell cycle. It deactivated ERK1/2 signalling and promoted mTOR signaling in A549 and NCI-H1819 cells to regulate cancer proliferation. Thus, tetrazole needs to be studied further as an anti-proliferative agent for treatment of lung cancer.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Autofagia/efeitos dos fármacos , Neoplasias Pulmonares/patologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Tetrazóis/farmacologia , Células A549 , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismo , Transdução de Sinais/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos
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