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1.
Bioresour Technol ; 410: 131297, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39153702

RESUMEN

Swine wastewater (SW) contains high levels of traditional pollutants, antibiotics, and antibiotic resistance genes (ARGs), necessitating effective elimination. Two parallel aerobic granular sludge (AGS) reactors, R1 and R2, were constructed and optimized for treating SW from two pig farms, identified as SW1 and SW2. R2 showed higher antibiotic removal efficiency, particularly in the removal of sulfonamides, while fluoroquinolones tended to adsorb onto the sludge. Process optimization by introducing an additional anoxic phase enhanced denitrification and reduced effluent ARG levels, also aiding in the improved removal of fluoroquinolones. The nitrite-oxidizing bacteria (NOB) Nitrospira accumulated after the treatment process, reaching 12.8 % in R1 and 14.1 % in R2, respectively. Mantel's test revealed that pH, NH4+-N, and Mg significantly affected ARGs and microbial community. Sulfadiazine and sulfamethazine were found to significantly impact ARGs and the microbial communities. This study provides innovative insights into the application of AGS for the treatment of real SW.


Asunto(s)
Antibacterianos , Aguas del Alcantarillado , Aguas Residuales , Animales , Aguas del Alcantarillado/microbiología , Antibacterianos/farmacología , Porcinos , Aguas Residuales/química , Aerobiosis , Farmacorresistencia Microbiana/genética , Purificación del Agua/métodos , Reactores Biológicos , Genes Bacterianos , Eliminación de Residuos Líquidos/métodos , Bacterias/genética , Bacterias/efectos de los fármacos , Bacterias/metabolismo , Contaminantes Químicos del Agua
2.
Biochem Biophys Res Commun ; 731: 150390, 2024 Oct 30.
Artículo en Inglés | MEDLINE | ID: mdl-39024980

RESUMEN

6-phosphogluconate dehydrogenase (6PGDH) is an essential enzyme in energy metabolism and redox reactions, and represents a potential drug target for the development of therapies targeting trypanosomes, plasmodium, or other pathogens. Tuberculosis, caused by Mycobacterium tuberculosis, is a contagious disease that severely affects human health, with approximately one-third of the world's population infected. However, the protein structure, exact oligomeric state, and catalytic mechanism of 6PGDH in Mycobacterium tuberculosis (Mt6PGDH) have remained largely unknown. In this study, we successfully purified and determined the structure of Mt6PGDH, revealing its function as a tetramer in both solution and crystal states. Through structural comparisons, we clarified the tetramer formation mechanism and the oligomeric organization of short-chain 6PGDHs. Additionally, we identified key residues for coenzyme recognition and catalytic activity. This work not only deepens our understanding of the enzymatic function of Mt6PGDH but also lays a foundation for the development of drugs targeting this enzyme.


Asunto(s)
Mycobacterium tuberculosis , Fosfogluconato Deshidrogenasa , Fosfogluconato Deshidrogenasa/química , Fosfogluconato Deshidrogenasa/metabolismo , Mycobacterium tuberculosis/enzimología , Cristalografía por Rayos X , Modelos Moleculares , Multimerización de Proteína , Proteínas Bacterianas/química , Proteínas Bacterianas/metabolismo , Secuencia de Aminoácidos , Conformación Proteica , Relación Estructura-Actividad , Dominio Catalítico
3.
Environ Pollut ; 357: 124482, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-38960118

RESUMEN

Pharmaceutical plant sites play a significant role in the dissemination of antibiotic resistance genes (ARGs) into the environment. It is imperative to comprehensively monitor of ARGs across various environmental media at these sites. This study focused on three pharmaceutical plants, two located in North China and one in South China. Through metagenomic approaches, we examined the composition, mobility potential, and bacterial hosts of ARGs in diverse media such as process water, groundwater, topsoil, soil cores, and pharmaceutical fermentation residues across diverse environmental matrices, including topsoil, soil cores, process water, groundwater, and pharmaceutical fermentation residues. We identified a wide array of ARGs, comprising 21 types and 740 subtypes, with process water exhibiting the highest abundance and diversity. Treatment processes varied in their efficacy in eliminating ARGs, and the clinically relevant ARGs should also be considered when evaluating wastewater treatment plant efficiency. Geographical distinctions in groundwater ARG distribution between northern and southern regions were observed. Soil samples from the three sites showed minimal impact from pharmaceutical activity, with vancomycin-resistance genes being the most prevalent. High levels of ARGs in pharmaceutical fermentation residues underscore the necessity for improved waste management practices. Metagenomic assembly revealed that plasmid-mediated ARGs were more abundant than chromosome-mediated ARGs. Metagenome-assembled genomes (MAGs) analysis identified 166 MAGs, with 62 harboring multiple ARGs. Certain bacteria tended to carry specific types of ARGs, revealing distinct host-resistance associations. This study enhances our understanding of ARG dissemination across different environmental media within pharmaceutical plants and underscores the importance of implementing strict regulations for effluent and residue discharge to control ARG spread.


Asunto(s)
Bacterias , Farmacorresistencia Microbiana , Metagenómica , China , Bacterias/genética , Bacterias/efectos de los fármacos , Farmacorresistencia Microbiana/genética , Microbiología del Suelo , Monitoreo del Ambiente , Farmacorresistencia Bacteriana/genética , Genes Bacterianos , Antibacterianos/farmacología , Agua Subterránea/microbiología , Agua Subterránea/química , Metagenoma
4.
Cell Commun Signal ; 22(1): 45, 2024 01 17.
Artículo en Inglés | MEDLINE | ID: mdl-38233864

RESUMEN

OBJECTIVES: Histological transformation to small cell lung cancer (SCLC) has been identified as a mechanism of TKIs resistance in EGFR-mutant non-small cell lung cancer (NSCLC). We aim to explore the prevalence of transformation in EGFR-wildtype NSCLC and the mechanism of SCLC transformation, which are rarely understood. METHODS: We reviewed 1474 NSCLC patients to investigate the NSCLC-to-SCLC transformed cases and the basic clinical characteristics, driver gene status and disease course of them. To explore the potential functional genes in SCLC transformation, we obtained pre- and post-transformation specimens and subjected them to a multigene NGS panel involving 416 cancer-related genes. To validate the putative gene function, we established knocked-out models by CRISPR-Cas 9 in HCC827 and A549-TP53-/- cells and investigated the effects on tumor growth, drug sensitivity and neuroendocrine phenotype in vitro and in vivo. We also detected the expression level of protein and mRNA to explore the molecular mechanism involved. RESULTS: We firstly reported an incidence rate of 9.73% (11/113) of SCLC transformation in EGFR-wildtype NSCLC and demonstrated that SCLC transformation is irrespective of EGFR mutation status (P = 0.16). We sequenced 8 paired tumors and identified a series of mutant genes specially in transformed SCLC such as SMAD4, RICTOR and RET. We firstly demonstrated that SMAD4 deficiency can accelerate SCLC transition by inducing neuroendocrine phenotype regardless of RB1 status in TP53-deficient NSCLC cells. Further mechanical experiments identified the SMAD4 can regulate ASCL1 transcription competitively with Myc in NSCLC cells and Myc inhibitor acts as a potential subsequent treatment agent. CONCLUSIONS: Transformation to SCLC is irrespective of EFGR status and can be accelerated by SMAD4 in non-small cell lung cancer. Myc inhibitor acts as a potential therapeutic drug for SMAD4-mediated resistant lung cancer. Video Abstract.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células Pequeñas , Humanos , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Receptores ErbB/genética , Neoplasias Pulmonares/patología , Mutación/genética , Inhibidores de Proteínas Quinasas/farmacología , Proteínas de Unión a Retinoblastoma/genética , Proteína Smad4/genética , Carcinoma Pulmonar de Células Pequeñas/genética , Carcinoma Pulmonar de Células Pequeñas/tratamiento farmacológico , Carcinoma Pulmonar de Células Pequeñas/patología , Ubiquitina-Proteína Ligasas/genética
5.
BMJ Open ; 13(12): e074963, 2023 12 10.
Artículo en Inglés | MEDLINE | ID: mdl-38072472

RESUMEN

INTRODUCTION: Bleomycin is a crucial and irreplaceable chemotherapy regimen for malignant ovarian germ cell tumours (MOGCTs) but its toxicities especially pulmonary fibrosis have limited the dose of treatment efficacy and decreased the patients' quality of life (QoL). Nintedanib has been approved for treating progressive fibrosing interstitial lung diseases and has shown potential anti-tumour effects. This study aims to evaluate the effectiveness and safety of nintedanib in the prevention of pulmonary fibrosis induced by bleomycin in MOGCTs patients. METHODS AND ANALYSIS: This is a multicentre, randomised, double-blinded, placebo-controlled clinical trial. We will enrol a total of 128 patients who will be randomly assigned to the nintedanib group and placebo group in a 1:1 ratio. Standard bleomycin, etoposide and cisplatin chemotherapy will be given to each MOGCT patient. In addition, patients assigned to nintedanib and the control group will be given oral nintedanib 150 mg two times per day and placebo one tablet two times per day until 1 month after the last cycle of bleomycin therapy, respectively. The primary outcome is the decline of forced vital capacity (FVC). The secondary outcomes are the decline of other pulmonary function indices (forced expiratory volume in 1 s; FVC pred%, carbon monoxide diffusion capacity) and the patients' QoL, oncological and fertility outcomes. We will use electronic case report forms to record all the participants' data and SPSS V.27.0/STATA V.16.0/Graphpad Prism V.8.0 to conduct statistical analysis. ETHICS AND DISSEMINATION: The Ethics Committee of Peking Union Medical College Hospital has approved the study (I-23PJ400). Written informed consent will be obtained from all participants/guardians. Study results will be submitted to peer-reviewed medical journals for publication and presented at academic conferences. TRIAL REGISTRATION NUMBER: ChiCTR2300070492.


Asunto(s)
Neoplasias de Células Germinales y Embrionarias , Fibrosis Pulmonar , Femenino , Humanos , Calidad de Vida , Bleomicina/efectos adversos , Método Doble Ciego , Resultado del Tratamiento , Neoplasias de Células Germinales y Embrionarias/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Multicéntricos como Asunto
6.
Oncology ; 101(12): 773-781, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38096801

RESUMEN

INTRODUCTION: The aim of the study was to evaluate the perioperative risks and outcomes of ultra-radical surgery in patients with extensive metastatic ovarian growing teratoma syndrome (GTS). METHODS: We conducted a retrospective study of patients with extensive metastatic ovarian GTS treated in our hospital between 2000 and 2022. Patients' clinical characteristics, surgical treatment, and outcomes were evaluated. RESULTS: Overall, 13 patients were identified, and the median age at diagnosis of ovarian immature teratoma (IT) was 24 years (range: 5-37). The median interval between IT diagnosis and presenting GTS was 8 months (range: 2-60), with a median surgery delay of 5 months (range: 3-300). Peritoneum and liver were the most commonly affected sites (100%), followed by bowel (12 patients, 92.3%), diaphragm (12 patients, 92.3%), adnexa (9 patients, 69.2%), omentum (8 patients, 61.5%), uterus (7 patients, 53.8%), in the descending order. The mean operation time was 316 min (range: 180-625), and the mean blood loss volume was 992 mL (range: 200-5,000). Peritoneal metastasectomy (13 patients, 100%), diaphragmatic metastasectomy (12 patients, 92.3%), metastasis removal from the bowel (8 patients, 61.5%), partial hepatectomy (4 patients, 30.8%), bowel excision and anastomosis (1 patient, 7.7%) were also applied to achieve optimal debulking. R0 was achieved in 9 (69.2%) patients. A high rate of intraoperative blood transfusion (8 patients, 61.5%) and admission to the intensive care unit (9 patients, 69.2%) were observed, and the median postoperative hospitalization time was 8 days (range: 4-22). After a median follow-up of 3.3 years, 9 patients were free of disease, and 4 were alive with stable residual diseases. CONCLUSION: The survival outcomes in extensive metastatic ovarian GTS were satisfactory after ultra-radical surgery, while a proper therapeutic plan should be established due to the high perioperative risks.


Asunto(s)
Neoplasias Ováricas , Teratoma , Femenino , Humanos , Preescolar , Niño , Adolescente , Adulto Joven , Adulto , Estudios Retrospectivos , Teratoma/cirugía , Teratoma/diagnóstico , Teratoma/patología , Neoplasias Ováricas/cirugía , Neoplasias Ováricas/tratamiento farmacológico , Pronóstico , Procedimientos Quirúrgicos de Citorreducción
7.
Gynecol Oncol ; 178: 145-152, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37865050

RESUMEN

OBJECTIVE: To evaluate the survival outcomes and establish a risk stratification system in patients with ovarian yolk sac tumors (OYST). METHODS: The recurrence-free survival (RFS), disease-specific survival (DSS), and prognostic factors were retrospectively evaluated in 151 OYST patients treated in our hospital between 2006 and 2022. A risk stratification system based on the identified prognostic factors was established. RESULTS: The median follow-up time was 5.1 years, with a 5-year RFS and DSS rate of 75.5% and 91.2%, respectively. FIGO stage III-IV and the interval between treatment and normalization of AFP were two prognostic predictors. Significant differences in RFS and DSS (both P < 0.001) were identified between patients who had normalized AFP ≤ 3 and ≥ 4 cycles of chemotherapy, or among patients who had normalized AFP after ≤2, 3-4, and ≥ 5 cycles of chemotherapy. FIGO stage I - II and stage III-IV were scored as 0 and 2, respectively. AFP normalization ≤2, 3, 4, and ≥ 5 cycles of chemotherapy were scored as 0, 1, 2, and 4, respectively. A total score of 0-1, 2-3, and ≥ 4 were stratified patients into low-risk (96 patients), intermediate-risk (35 patients), and high-risk groups (20 patients), respectively. Patients in three risk stratifications manifested significant differences in both RFS and DSS (P < 0.0001). CONCLUSION: This risk stratification system based on tumor stage and the interval between treatment and normalization of AFP may help to guide clinical management by dividing OYST patients into three risk groups.


Asunto(s)
Tumor del Seno Endodérmico , Neoplasias Ováricas , Femenino , Humanos , Estadificación de Neoplasias , alfa-Fetoproteínas , Tumor del Seno Endodérmico/patología , Estudios Retrospectivos , Pronóstico , Neoplasias Ováricas/tratamiento farmacológico , Medición de Riesgo
8.
iScience ; 26(9): 107604, 2023 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-37664592

RESUMEN

The spliceosomal snRNP cores, each comprised of a snRNA and a seven-membered Sm ring (D1/D2/F/E/G/D3/B), are assembled by twelve chaperoning proteins in human. However, only six assembly-assisting proteins, ICln and the SMN complex (SMN/Gemin2/Gemin6-8), have been found in Schizosaccharomyces pombe (Sp). Here, we used recombinant proteins to reconstitute the chaperone machinery and investigated the roles of these proteins systematically. We found that, like the human system, the assembly in S. pombe requires ICln and the SMN complex sequentially. However, there are several significant differences. For instance, h_F/E/G forms heterohexamers and heterotrimers, while Sp_F/E/G only forms heterohexamers; h_Gemin2 alone can bind D1/D2/F/E/G, but Sp_Gemin2 cannot. Moreover, we found that Sp_Gemin2 is essential using genetic approaches. These mechanistic studies reveal that these six proteins are necessary and sufficient for Sm core assembly at the molecular level, and enrich our understanding of the chaperone systems in species variation and evolution.

9.
ACS Omega ; 8(25): 22331-22344, 2023 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-37396245

RESUMEN

In comparison with sensible heat storage devices, phase change thermal storage devices have advantages such as high heat storage density, low heat dissipation loss, and good cyclic performance, which have great potential for solving the problem of temporal and spatial imbalances in the transfer and utilization of heat energy. However, there are also issues such as the small thermal conductivity of phase change materials (PCMs) and poor efficiency in heat storage and release, and in recent years, enhanced heat transfer in phase change thermal storage devices has become one of the research hotspots for optimizing thermal storage devices. Although there have been reviews of enhanced heat transfer technology for phase change thermal storage devices in the literature, there is still insufficient research on the summarization of the enhanced heat transfer mechanism, structural optimization, and applications of phase change thermal storage devices. This Review provides a review of enhanced heat transfer in phase change thermal storage devices from two aspects: internal structure enhanced heat transfer and heat exchange medium flow channel enhanced heat transfer. It summarizes the enhanced heat transfer measures of various types of phase change thermal storage devices and discusses the role of structural parameters in enhanced heat transfer. It is hoped that this Review will provide some references for scholars engaged in research on phase change thermal storage heat exchangers.

10.
Sensors (Basel) ; 23(10)2023 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-37430658

RESUMEN

Currently, Low-Rate Denial of Service (LDoS) attacks are one of the main threats faced by Software-Defined Wireless Sensor Networks (SDWSNs). This type of attack uses a lot of low-rate requests to occupy network resources and hard to detect. An efficient detection method has been proposed for LDoS attacks with the features of small signals. The non-smooth small signals generated by LDoS attacks are analyzed employing the time-frequency analysis method based on Hilbert-Huang Transform (HHT). In this paper, redundant and similar Intrinsic Mode Functions (IMFs) are removed from standard HHT to save computational resources and to eliminate modal mixing. The compressed HHT transformed one-dimensional dataflow features into two-dimensional temporal-spectral features, which are further input into a Convolutional Neural Network (CNN) to detect LDoS attacks. To evaluate the detection performance of the method, various LDoS attacks are simulated in the Network Simulator-3 (NS-3) experimental environment. The experimental results show that the method has 99.8% detection accuracy for complex and diverse LDoS attacks.

11.
Micromachines (Basel) ; 14(6)2023 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-37374831

RESUMEN

As the world's population ages, technologies that enable long-term non-contact monitoring of patients are of great research significance. For this purpose, we propose a multi-person 2-D positioning method based on a 77 GHz FMCW radar. In this method, we first perform beam scanning processing on the data cube acquired by the radar and obtain the distance-Doppler-angle data cube. Then, we eliminate interfering targets through a multi-channel respiratory spectrum superposition algorithm. Finally, we obtain the distance and angle information of the target by the target center selection method. The experimental results show that the proposed method can detect the distance and angle information of multiple people.

12.
Heliyon ; 9(6): e17364, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37342585

RESUMEN

The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had a significant impact on global health. To address the urgent need for plasmids containing SARS-CoV-2 sequences in research, we have developed a high-throughput FastCloning platform for the construction of associated plasmids. Our platform uses a FastCloning method to construct a plasmid library from 29 ORFs of the virus and 20 commonly used vectors in the lab. The library contains 536 recombinant vectors, with a highly positive clone success rate of 92.4%. Our study provides a rapid and efficient approach to constructing a large plasmid library for SARS-CoV-2 research.

13.
Dermatol Surg ; 49(5S): S34-S40, 2023 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-37115998

RESUMEN

BACKGROUND: Dermatologists have been looking for ways to improve wound healing and postoperative scar appearance. The safety and efficacy of botulinum toxin type A (BTXA) in the prevention and treatment on pathological scars have become the current research hotspot since it was approved by the US FDA in medical cosmetology in 2002. PURPOSE: This article aims to provide an overview of the clinical research, limitations, and application prospects of BTXA in the prevention and treatment of traumatic or postoperative pathological scars, which can provide a reference and better understanding of relevant studies. METHODS: The current research progress was summarized and discussed, with new problems and research ideas being proposed ranging from the molecular mechanism of BTXA in preventing and treating pathological scars to its clinical application via investigation and reference research. RESULTS: BTXA is effective in relieving itching and pain associated with pathological scars, limiting scar hyperplasia along with preventing scar contracture, but the specific mechanism is still not clear. CONCLUSION: Most of the clinicians have confirmed the clinical effectiveness of BTXA in the prevention and treatment of pathological scars, yet its mode of action and combination therapy need more research.


Asunto(s)
Toxinas Botulínicas Tipo A , Cicatriz , Humanos , Cicatriz/tratamiento farmacológico , Cicatriz/etiología , Cicatriz/prevención & control , Fibroblastos , Resultado del Tratamiento , Cicatrización de Heridas
14.
Chemosphere ; 313: 137508, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36493889

RESUMEN

The biotransformation of sulfamonomethoxine (SMM) was studied in an aerobic granular sludge (AGS) system to understand the role of sorption by microbial cells and extracellular polymeric substances (EPS) and the role of functional microbe/enzyme biodegradation. Biodegradation played a more important role than adsorption, while microbial cells covered with tightly bound EPS (TB-EPS) showed higher adsorption capacity than microbial cells themselves or microbial cells covered with both loosely bound EPS (LB-EPS) and TB-EPS. The binding tests between EPS and SMM and the spectroscopic analyses (3D-EEM, UV-Vis, and FTIR) were performed to obtain more information about the adsorption process. The data showed that SMM could interact with EPS by combining with aromatic protein compounds, fulvic acid-like substances, protein amide II, and nucleic acids. Batch tests with various substances showed that SMM removal rates were in an order of NH2OH (60.43 ± 2.21 µg/g SS) > NH4Cl (52.96 ± 0.30 µg/g SS) > NaNO3 (31.88 ± 1.20 µg/g SS) > NaNO2 (21.80 ± 0.42 µg/g SS). Hydroxylamine and hydroxylamine oxidoreductase (HAO) favored SMM biotransformation and the hydroxylamine-mediated biotransformation of SMM was more effective than others. In addition, both ammonia monooxygenase (AMO) and CYP450 were able to co-metabolize SMM. Analysis of UPLC-QTOF-MS indicated the biotransformation mechanisms, revealing that acetylation of arylamine, glucuronidation of sulfonamide, deamination, SO2 extrusion, and δ cleavage were the five major transformation pathways. The detection of TP202 in the hydroxylamine-fed Group C indicated a new biotransformation pathway through HAO. This study contributes to a better understanding of the biotransformation of SMM.


Asunto(s)
Aguas del Alcantarillado , Sulfamonometoxina , Aguas del Alcantarillado/química , Análisis Espectral , Biotransformación , Hidroxilaminas
15.
Micromachines (Basel) ; 13(11)2022 Nov 11.
Artículo en Inglés | MEDLINE | ID: mdl-36422389

RESUMEN

This paper proposes a real-time heart rate detection method based on 77 GHz FMCW radar. Firstly, the method establishes a new motion model according to respiratory and heartbeat rules, and extracts the motion signals of the chest and the abdomen; then, the random body motion (RBM) signal is eliminated by a combination of polynomial fitting and recursive least squares (RLS) adaptive filtering; lastly, multi-detection-point adaptive harmonics cancellation (AHC) is used to eliminate respiratory harmonics. In addition, the method introduces a spectrum analysis algorithm based on linear predictive coding (LPC). The experimental results show that the method can effectively eliminate the RBM signal and respiratory harmonics, and that the average real-time heart rate detection error rate is 2.925%.

16.
Artículo en Inglés | MEDLINE | ID: mdl-35942366

RESUMEN

Objective: The lung is the second most common site of colorectal cancer (CRC) metastasis. This study aims to investigate the therapeutic effects and potential action mechanisms of Yifei Jianpi Tongfu formula (YJTF) in CRC lung metastasis in a comprehensive and systematic way by network analysis, molecular docking, and experimental verification. Methods: The main ingredients in YJTF were screened from the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP) and Traditional Chinese Medicine Integrated Database (TCMID), and the disease-related targets from the Online Mendelian Inheritance in Man (OMIM) and GeneCards and the compound-related targets from SwissTargetPrediction were collected. Then, Metascape was used for pathway annotation and enrichment analysis, and meanwhile, a protein-protein interaction (PPI) network was constructed. Molecular docking was carried out to investigate interactions between the active compounds and the potential targets. The in vivo effect of YJTF on CRC lung metastasis was observed in a tail vein injection mouse model. Results: A total of 243 active compounds and 81 disease-related targets of YJTF were selected for analysis. The results of multiple network analysis showed that the core targets of YJTF were enriched onto various cancer-related pathways, especially focal adhesion and adherens junction. The results of molecular docking demonstrated that all core compounds (quercetin, kaempferol, luteolin, apigenin, and isorhamnetin) were capable of binding with AKT1, EGFR, SRC, ESR1, and PTGS2. Experimental validation in vivo demonstrated that YJTF combined with oxaliplatin could significantly reduce the number of lung metastases and improve the quality of life in mice. Further research suggested that YJTF inhibited CRC lung metastasis probably by modulating epithelial-to-mesenchymal transition (EMT). Conclusions: According to the analysis, YJTF can be considered as an effective adjuvant therapy for CRC lung metastasis.

17.
ACS Omega ; 7(2): 2364-2376, 2022 Jan 18.
Artículo en Inglés | MEDLINE | ID: mdl-35071924

RESUMEN

Three-dimensional (3D) culture via micropattern arrays to generate cellular spheroids seems a promising in vitro biomimetic system for liver tissue engineering applications, such as drug screening. Recently, organ-derived decellularized extracellular matrix emerges as arguably the most biomimetic bioink. Herein, decellularized liver matrix (DLM)-derived micropattern array chips were developed to fabricate size-controllable and arrangement-orderly HepG2 spheroids for drug screening. The porcine DLM was obtained by the removal of cellular components and then ground into powder, followed by enzymolysis. DLM as a coating substrate was compared with collagen type I (Col I) and Matrigel in terms of biological performance for enhancing cell adhesion, proliferation, and functions. Subsequently, we used poly(dimethylsiloxane) (PDMS) to adsorb DLM as the bioink to fabricate micropattern array chips. The optimal shape and size of micropattern were determined by evaluating the morphology, viability, and functions of HepG2 3D cellular aggregates. In addition, drug-susceptibility testing (paclitaxel, doxorubicin HCl, and disulfiram) was performed on this novel platform. The DLM provided the tissue-specific microenvironment that provided suitable supports for HepG2 cells, compared to Col I and Matrigel. A circular micropattern with a diameter of 100 µm was the optimal processing parameter to rapidly fabricate large-scale, size-controllable, and arrangement-orderly HepG2 cellular aggregates with 3D spheroid's shape and high cell viability. Drug screening testing showed that the effect of a drug could be directly demonstrated on-chip by confocal microscopy measuring the viability of spheroids. We provide a novel platform for the large-scale generation of HepG2 spheroids with uniform size and arrangement, thus bringing convenience, reducing error, and increasing reproducibility for a rapid drug discovery by fluorescence quantitative analysis. This methodology may be possible to apply in advancing personalized medicine and drug discovery.

18.
Front Mol Biosci ; 8: 684866, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34055896

RESUMEN

BACKGROUND: Pancreatic cancer (PC) is an aggressive malignancy and has a poor prognosis. Although emerging research has revealed that circular RNAs (circRNAs) are crucial modulators that control tumor development and metastasis, their functional involvement in PC has not been well characterized. Here, we examined whether and how circRNA circ_0001666 governs epithelial-mesenchymal transition (EMT) in PC. METHODS: We investigated the effects of circ_0001666 on EMT and PC cell invasion by gain- and loss-of-function assays. We also explored the mechanisms underlying the functions of circ_0001666 in PC cells. RESULTS: We found that circ_0001666 is highly expressed in PC tissues and PC cell lines. Patients with high circ_0001666 expression had shorter survival times. In vitro and in vivo experiments have demonstrated that upregulation of circ_0001666 facilitates PC cell proliferation, EMT and invasiveness, whereas knockdown of circ_0001666 exhibits opposite functions. Moreover, circ_0001666 is able to bind to miR-1251, thus increasing the expression of SOX4, which is a direct downstream effector of miR-1251. The oncogenic effects of circ_0001666 on EMT and PC cell invasion were rescued by miR-1251 overexpression. CONCLUSIONS: These results suggested that circ_0001666 acts as an oncogenic circRNA to promote EMT and invasion of PC cells through sponging miR-1251, and indicated that circ_0001666 could be explored as a potential therapeutic target for PC.

19.
ACS Appl Mater Interfaces ; 13(11): 12639-12648, 2021 Mar 24.
Artículo en Inglés | MEDLINE | ID: mdl-32897697

RESUMEN

Magnetic soft materials (MSMs) have shown potential in soft robotics, actuators, metamaterials, and biomedical devices because they are capable of untethered, fast, and reversible shape reconfigurations as well as controllable dynamic motions under applied magnetic fields. Recently, magnetic shape memory polymers (M-SMPs) that incorporate hard magnetic particles in shape memory polymers demonstrated superior shape manipulation performance by realizing reprogrammable, untethered, fast, and reversible shape transformation and shape locking in one material system. In this work, we develop a multimaterial printing technology for the complex structural integration of MSMs and M-SMPs to explore their enhanced multimodal shape transformation and tunable properties. By cooperative thermal and magnetic actuation, we demonstrate multiple deformation modes with distinct shape configurations, which further enable active metamaterials with tunable physical properties such as sign-change Poisson's ratio. Because of the multiphysics response of the M-MSP/MSM metamaterials, one distinct feature is their capability of shifting between various global mechanical behaviors such as expansion, contraction, shear, and bending. We anticipate that the multimaterial printing technique opens new avenues for the fabrication of multifunctional magnetic materials.

20.
Angew Chem Int Ed Engl ; 59(31): 12580-12583, 2020 07 27.
Artículo en Inglés | MEDLINE | ID: mdl-32691958

RESUMEN

Cupin proteins share a double-stranded ß-helix fold, form one of the largest protein superfamilies, and possess remarkable functional diversity. They usually exist in homooligomeric states. Goss and co-workers recently reported that the cupin protein Pac13, which is a dehydratase that mediates the formation of the 3'-deoxy nucleoside of pacidamycins, is an unusual small monomer. However, a careful analysis of the biophysical and structural data provided by the authors suggests that Pac13 is in fact a homodimer, similar to many other cupin proteins.


Asunto(s)
Proteínas Bacterianas/química , Hidroliasas/química , Proteínas Bacterianas/metabolismo , Cristalografía por Rayos X , Hidroliasas/metabolismo , Interacciones Hidrofóbicas e Hidrofílicas , Unión Proteica , Multimerización de Proteína , Estructura Cuaternaria de Proteína , Streptomyces/química
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