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1.
Semin Neurol ; 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38621706

RESUMO

Posttraumatic epilepsy (PTE) is a complication of traumatic brain injury that can increase morbidity, but predicting which patients may develop PTE remains a challenge. Much work has been done to identify a variety of risk factors and biomarkers, or a combination thereof, for patients at highest risk of PTE. However, several issues have hampered progress toward fully adapted PTE models. Such issues include the need for models that are well-validated, cost-effective, and account for competing outcomes like death. Additionally, while an accurate PTE prediction model can provide quantitative prognostic information, how such information is communicated to inform shared decision-making and treatment strategies requires consideration of an individual patient's clinical trajectory and unique values, especially given the current absence of direct anti-epileptogenic treatments. Future work exploring approaches integrating individualized communication of prediction model results are needed.

2.
J Sci Food Agric ; 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38567804

RESUMO

BACKGROUND: As the major protein (approximately 36%) in rice bran, globulin exhibits excellent foaming and emulsifying properties, endowing its useful application as a foaming and emulsifying agent in the food industry. However, the low water solubility restricts its commercial potential in industrial applications. The present study aimed to improve this protein's processing and functional properties. RESULTS: A novel covalent complex was fabricated by a combination of the Maillard reaction and alkaline oxidation using rice bran globulin (RBG), chitooligosaccharide (C), quercetin (Que) and resveratrol (Res). The Maillard reaction improved the solubility, emulsifying and foaming properties of RBG. The resultant glycosylated protein was covalently bonded with quercetin and resveratrol to form a (RBG-C)-Que-Res complex. (RBG-C)-Que-Res exhibited higher thermal stability and antioxidant ability than the native protein, binary globulin-chitooligosaccharide or ternary globulin-chitooligosaccharide-polyphenol (only containing quercetin or resveratrol) conjugates. (RBG-C)-Que-Res exerted better cytoprotection against the generation of malondialdehyde and reactive oxygen species in HepG2 cells, which was associated with increased activities of antioxidative enzymes superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) through upregulated genes SOD1, CAT, GPX1 (i.e. gene for glutathione peroxidase-1), GCLM (i.e. gene for glutamate cysteine ligase modifier subunit), SLC1A11 (i.e. gene for solute carrier family 7, member 11) and SRXN1 (i.e. gene for sulfiredoxin-1). The anti-apoptotic effect of (RBG-C)-Que-Res was confirmed by the downregulation of caspase-3 and p53 and the upregulation of B-cell lymphoma-2 gene expression. CONCLUSION: The present study highlights the potential of (RBG-C)-Que-Res conjugates as functional ingredients in healthy foods. © 2024 Society of Chemical Industry.

3.
NPJ Breast Cancer ; 10(1): 14, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38374091

RESUMO

HER2/ERBB2 evaluation is necessary for treatment decision-making in breast cancer (BC), however current methods have limitations and considerable variability exists. DNA copy number (CN) evaluation by droplet digital PCR (ddPCR) has complementary advantages for HER2/ERBB2 diagnostics. In this study, we developed a single-reaction multiplex ddPCR assay for determination of ERBB2 CN in reference to two control regions, CEP17 and a copy-number-stable region of chr. 2p13.1, validated CN estimations to clinical in situ hybridization (ISH) HER2 status, and investigated the association of ERBB2 CN with clinical outcomes. 909 primary BC tissues were evaluated and the area under the curve for concordance to HER2 status was 0.93 and 0.96 for ERBB2 CN using either CEP17 or 2p13.1 as reference, respectively. The accuracy of ddPCR ERBB2 CN was 93.7% and 94.1% in the training and validation groups, respectively. Positive and negative predictive value for the classic HER2 amplification and non-amplification groups was 97.2% and 94.8%, respectively. An identified biological "ultrahigh" ERBB2 ddPCR CN group had significantly worse survival within patients treated with adjuvant trastuzumab for both recurrence-free survival (hazard ratio, HR: 3.3; 95% CI 1.1-9.6; p = 0.031, multivariable Cox regression) and overall survival (HR: 3.6; 95% CI 1.1-12.6; p = 0.041). For validation using RNA-seq data as a surrogate, in a population-based SCAN-B cohort (NCT02306096) of 682 consecutive patients receiving adjuvant trastuzumab, the ultrahigh-ERBB2 mRNA group had significantly worse survival. Multiplex ddPCR is useful for ERBB2 CN estimation and ultrahigh ERBB2 may be a predictive factor for decreased long-term survival after trastuzumab treatment.

4.
Cancer Genomics Proteomics ; 20(6suppl): 763-770, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38035709

RESUMO

BACKGROUND/AIM: Circulating tumor DNA (ctDNA), which is shed from cancer cells into the bloodstream, offers a potential minimally invasive approach for cancer diagnosis and monitoring. This research aimed to assess the preoperative ctDNA levels in ovarian tumors patients' plasma and establish correlations with clinicopathological parameters and patient prognosis. PATIENTS AND METHODS: Tumor DNA was extracted from ovarian tumor tissue from 41 patients. Targeted sequencing using a panel of 127 genes recurrently mutated in cancer was performed to identify candidate somatic mutations in the tumor DNA. SAGAsafe digital PCR (dPCR) assays targeting the candidate mutations were used to measure ctDNA levels in patient plasma samples, obtained prior to surgery, to evaluate ctDNA levels in terms of mutant copy number/ml and variant allele frequency. RESULTS: Somatic mutations were found in 24 tumor samples, 17 of which were from ovarian cancer patients. The most frequently mutated gene was TP53. Preoperative plasma ctDNA levels were detected in 14 of the 24 patients. With higher stage, plasma ctDNA mutant concentration increased (p for trend <0.001). The overall survival of cancer patients with more than 10 ctDNA mutant copies/ml in plasma was significantly worse (p=0.008). CONCLUSION: Pre-operative ctDNA measurement in ovarian cancer patients' plasma holds promise as a predictive biomarker for tumor staging and prognosis.


Assuntos
DNA de Neoplasias , Neoplasias Ovarianas , Humanos , Feminino , DNA de Neoplasias/genética , Prognóstico , Mutação , Estadiamento de Neoplasias , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/cirurgia , Biomarcadores Tumorais/genética
5.
J Transl Med ; 21(1): 696, 2023 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-37798736

RESUMO

BACKGROUND: Breast cancer is, despite screening, not always detected early enough and is together with other tumor types known to shed genetic information in circulation. Unlike single-copy nuclear DNA, mitochondrial DNA (mtDNA) copies range from 100s to 10,000s per cell, thus providing a potentially alternative to identify potential missing cancer information in circulation at an early stage. METHODS: To characterize mitochondrial mutation landscapes in breast cancer, whole mtDNA sequencing and bioinformatics analyses were performed on 86 breast cancer biopsies and 50 available matched baseline cancer-free whole blood samples from the same individuals, selected from a cohort of middle-aged women in Sweden. To determine whether the mutations can be detected in blood plasma prior to cancer diagnosis, we further designed a nested case-control study (n = 663) and validated the shortlisted mutations using droplet digital PCR. RESULTS: We detected different mutation landscapes between biopsies and matched whole blood samples. Compared to whole blood samples, mtDNA from biopsies had higher heteroplasmic mutations in the D-loop region (P = 0.02), RNR2 (P = 0.005), COX1 (P = 0.037) and CYTB (P = 0.006). Furthermore, the germline mtDNA mutations had higher heteroplasmy level than the lost (P = 0.002) and de novo mutations (P = 0.04). The nonsynonymous to synonymous substitution ratio (dN/dS) was higher for the heteroplasmic mutations (P = 7.25 × 10-12) than that for the homoplasmic mutations, but the de novo (P = 0.06) and lost mutations (P = 0.03) had lower dN/dS than the germline mutations. Interestingly, we found that the critical regions for mitochondrial transcription: MT-HSP1 (odds ratio [OR]: 21.41), MT-TFH (OR: 7.70) and MT-TAS2 (OR: 3.62), had significantly higher heteroplasmic mutations than the rest of the D-loop sub-regions. Finally, we found that the presence of mt.16093T > C mutation increases 67% risk of developing breast cancer. CONCLUSIONS: Our findings show that mitochondrial genetic landscape changes during cancer pathogenesis and positive selection of mtDNA heteroplasmic mutations in breast cancer. Most importantly, the mitochondrial mutations identified in biopsies can be traced back in matched plasma samples and could potentially be used as early breast cancer diagnostic biomarkers.


Assuntos
Neoplasias da Mama , Pessoa de Meia-Idade , Humanos , Feminino , Neoplasias da Mama/genética , Estudos de Casos e Controles , Mutação/genética , DNA Mitocondrial/genética , Mutação em Linhagem Germinativa
6.
Chemosphere ; 341: 140101, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37690557

RESUMO

As the climate seriously changes, ecofriendly nanomaterials have attracted tremendous interest in renewable energy as photocatalysis. Herein, we designed a new green bismuth-based Z-scheme Bi2O22+ slabs coordinate with 2-aminoterephthalic acid (N-BOB)/BiOIO3 through a simple anion exchange and postsynthetic hydrothermal reaction. FTIR, XRD, FESEM and TEM were employed to characterize the functional groups, structure, and morphologies. UV-DRS revealed the difference in band energy of the N-BOB and N-BOB/BiOIO3. Toward Rh B, TC and CIP degradation tests, 1-N-BOB/BiOIO3 manifests the best photocatalytic degradation (52.3%, 63.6% and 30.2%) efficiency. Also, 1-N-BOB/BiOIO3 possesses high durability in photocatalytic reactions and can inhibit 32.3% of bacterial growth. The results indicate that the synergistic effect between surface amine groups and Z-scheme heterojunction harvests light absorption to increase solar-to-energy (STE) efficiency, accelerate the charge separation, and increases the active sites with high photoredox potential, thus improving the photocatalytic performance. ROS scavenging tests further elucidated that photogenerated holes and hydroxyl radicals play a critical role. In addition, the surface amine groups and benzene rings can be utilized for supercapacitors and other multidisciplinary applications. 0.5 N-BOB/BiOIO3/GO impressively showed 5 times higher specific capacitance than pure GO electrode. We hope this work provides new sight into designing green nanomaterials to relieve environmental pollution and leave behind a clean future for the next generation.


Assuntos
Bismuto , Clima , Capacitância Elétrica , Aminas
7.
Sensors (Basel) ; 23(17)2023 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-37687841

RESUMO

With the increasing use of automated vehicles (AVs) in the coming decades, government authorities and private companies must leverage their potential disruption to benefit society. Few studies have considered the impact of AVs towards mode shift by considering a range of factors at the city level, especially in Australia. To address this knowledge gap, we developed a system dynamic (SD)-based model to explore the mode shift between conventional vehicles (CVs), AVs, and public transport (PT) by systematically considering a range of factors, such as road network, vehicle cost, public transport supply, and congestion level. By using Melbourne's Transport Network as a case study, the model simulates the mode shift among AVs, CVs, and PT modes in the transportation system over 50 years, starting from 2018, with the adoption of AVs beginning in 2025. Inputs such as current traffic, road capacity, public perception, and technological advancement of AVs are used to assess the effects of different policy options on the transport systems. The data source used is from the Victorian Integrated Transport Model (VITM), provided by the Department of Transport and Planning, Melbourne, Australia, data from the existing literature, and authors' assumptions. To our best knowledge, this is the first time using an SD model to investigate the impacts of AVs on mode shift in the Australian context. The findings suggest that AVs will gradually replace CVs as another primary mode of transportation. However, PT will still play a significant role in the transportation system, accounting for 50% of total trips by person after 2058. Cost is the most critical factor affecting AV adoption rates, followed by road network capacity and awareness programs. This study also identifies the need for future research to investigate the induced demand for travel due to the adoption of AVs and the application of equilibrium constraints to the traffic assignment model to increase model accuracy. These findings can be helpful for policymakers and stakeholders to make informed decisions regarding AV adoption policies and strategies.

8.
J Chin Med Assoc ; 86(9): 859-864, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37462444

RESUMO

BACKGROUND: Remote reporting is an important preventive measure against coronavirus disease 2019 (COVID-19) for radiology departments; it reduces the chance of cross-infections between coworkers. The purpose of this study was to evaluate how the preferred locations that radiologists filed reports from changed in response to COVID-19 by measuring the use of internal teleradiology workstations. METHODS: Data were obtained from the radiological information system (RIS) database at our institution, which recorded the reporting workstation for each radiological examination. The reporting activities in 2021 were divided into computed radiography (CR) and computed tomography (CT)/magnetic resonance imaging (MRI) groups. The Wilcoxon signed-rank test was used to measure differences in the use of off-site workstations in prepandemic, midpandemic, and postpandemic periods. RESULTS: There were statistically significant increases in the number of reports filed from off-site workstations for each attending physician from the prepandemic period to the midpandemic period in both the CR (15.1%-25.4%, p = 0.041) and CT/MRI (18.9%-28.7%, p = 0.006) groups. There was no significant difference noted between the prepandemic and postpandemic periods for either the CR (15.1% vs 18.4%, p = 0.727) or CT/MRI group (18.9% vs 23.3%, p = 0.236). CONCLUSION: In response to the COVID-19 outbreak, radiologists used internal teleradiology to report CR and CT/MRI examinations significantly more frequently. In contrast to the predictions of previous studies, the use of internal teleradiology returned to baseline levels after the pandemic was under control.


Assuntos
COVID-19 , Sistemas de Informação em Radiologia , Telerradiologia , Humanos , Pandemias , Telerradiologia/métodos , Radiologistas
9.
Biomater Sci ; 11(14): 4995-5011, 2023 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-37334517

RESUMO

Atopic dermatitis (AD) is a chronic, relapsing inflammatory disorder that requires long-term treatment to achieve optimal control. Topical corticosteroids or calcineurin inhibitors are the mainstay of treatment, but the safety and efficacy of their daily use remain a concern. Here, we report a double-layered poly(lactic-co-glycolic acid) (PLGA)/sodium hyaluronate (HA) microneedle (MN) patch as a long-acting formulation for sustained delivery of natural polyphenols, curcumin (CUR) and gallic acid (GA), into the inflamed skin. Upon insertion into the skin, the HA layer is rapidly dissolved within 5 min for triggering GA release; the PLGA tip is embedded into the dermis for sustained release of CUR for 2 months. Initially, CUR and GA are simultaneously released from the MNs to exert synergistic antioxidant and anti-inflammatory effects, thus promptly relieving AD symptoms. After the complete release of GA, the extended CUR release can maintain the improvement obtained for at least 56 days. Our results revealed that compared with the CUR-only MN and untreated AD groups, the administration of CUR/GA-loaded MNs not only rapidly reduced the dermatitis score from Day 2 but also significantly inhibited epidermal hyperplasia and mast cell accumulation, reduced serum IgE and histamine levels, and downregulated reactive oxygen species production in the skin lesions of Nc/Nga mice on Day 56. These findings demonstrated that the double-layered PLGA/HA MN patch can serve as an effective dual-polyphenol delivery system for rapid and long-term management of AD.


Assuntos
Curcumina , Dermatite Atópica , Camundongos , Animais , Dermatite Atópica/tratamento farmacológico , Dermatite Atópica/patologia , Polifenóis/farmacologia , Pele , Sistemas de Liberação de Medicamentos , Curcumina/farmacologia
10.
Chem Commun (Camb) ; 59(42): 6339-6342, 2023 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-37186113

RESUMO

3D SERS microneedles with self-assembled AuNPs were fabricated with tannic acid (chemical glue and reductant) on polylactic acid microneedles for in-depth chemical and biomolecular analysis, with LOD values below 200 ppb for small molecules and 102 CFU cm-2 for bacteria. The MB/Au-microneedles were used for photodynamic therapy with SERS-monitored photosensitizer degradation.


Assuntos
Nanopartículas Metálicas , Fotoquimioterapia , Ouro/química , Nanopartículas Metálicas/química , Polifenóis , Análise Espectral Raman
11.
Nature ; 616(7955): 159-167, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-37020004

RESUMO

A complete understanding of how exposure to environmental substances promotes cancer formation is lacking. More than 70 years ago, tumorigenesis was proposed to occur in a two-step process: an initiating step that induces mutations in healthy cells, followed by a promoter step that triggers cancer development1. Here we propose that environmental particulate matter measuring ≤2.5 µm (PM2.5), known to be associated with lung cancer risk, promotes lung cancer by acting on cells that harbour pre-existing oncogenic mutations in healthy lung tissue. Focusing on EGFR-driven lung cancer, which is more common in never-smokers or light smokers, we found a significant association between PM2.5 levels and the incidence of lung cancer for 32,957 EGFR-driven lung cancer cases in four within-country cohorts. Functional mouse models revealed that air pollutants cause an influx of macrophages into the lung and release of interleukin-1ß. This process results in a progenitor-like cell state within EGFR mutant lung alveolar type II epithelial cells that fuels tumorigenesis. Ultradeep mutational profiling of histologically normal lung tissue from 295 individuals across 3 clinical cohorts revealed oncogenic EGFR and KRAS driver mutations in 18% and 53% of healthy tissue samples, respectively. These findings collectively support a tumour-promoting role for  PM2.5 air pollutants  and provide impetus for public health policy initiatives to address air pollution to reduce disease burden.


Assuntos
Adenocarcinoma de Pulmão , Poluentes Atmosféricos , Poluição do Ar , Transformação Celular Neoplásica , Neoplasias Pulmonares , Animais , Camundongos , Adenocarcinoma de Pulmão/induzido quimicamente , Adenocarcinoma de Pulmão/genética , Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/análise , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Transformação Celular Neoplásica/induzido quimicamente , Transformação Celular Neoplásica/efeitos dos fármacos , Transformação Celular Neoplásica/genética , Exposição Ambiental , Receptores ErbB/genética , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/genética , Material Particulado/efeitos adversos , Material Particulado/análise , Tamanho da Partícula , Estudos de Coortes , Macrófagos Alveolares/efeitos dos fármacos , Células Epiteliais Alveolares/efeitos dos fármacos , Células Epiteliais Alveolares/patologia
12.
IEEE Trans Pattern Anal Mach Intell ; 45(4): 4416-4429, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35939470

RESUMO

Camera-based 3D object detectors are welcome due to their wider deployment and lower price than LiDAR sensors. We first revisit the prior stereo detector DSGN for its stereo volume construction ways for representing both 3D geometry and semantics. We polish the stereo modeling and propose the advanced version, DSGN++, aiming to enhance effective information flow throughout the 2D-to-3D pipeline in three main aspects. First, to effectively lift the 2D information to stereo volume, we propose depth-wise plane sweeping (DPS) that allows denser connections and extracts depth-guided features. Second, for grasping differently spaced features, we present a novel stereo volume - Dual-view Stereo Volume (DSV) that integrates front-view and top-view features and reconstructs sub-voxel depth in the camera frustum. Third, as the foreground region becomes less dominant in 3D space, we propose a multi-modal data editing strategy - Stereo-LiDAR Copy-Paste, which ensures cross-modal alignment and improves data efficiency. Without bells and whistles, extensive experiments in various modality setups on the popular KITTI benchmark show that our method consistently outperforms other camera-based 3D detectors for all categories. Code is available at https://github.com/chenyilun95/DSGN2.

13.
J Neurol Neurosurg Psychiatry ; 94(3): 245-249, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36241423

RESUMO

BACKGROUND: Post-traumatic epilepsy (PTE) is a severe complication of traumatic brain injury (TBI). Electroencephalography aids early post-traumatic seizure diagnosis, but its optimal utility for PTE prediction remains unknown. We aim to evaluate the contribution of quantitative electroencephalograms to predict first-year PTE (PTE1). METHODS: We performed a multicentre, retrospective case-control study of patients with TBI. 63 PTE1 patients were matched with 63 non-PTE1 patients by admission Glasgow Coma Scale score, age and sex. We evaluated the association of quantitative electroencephalography features with PTE1 using logistic regressions and examined their predictive value relative to TBI mechanism and CT abnormalities. RESULTS: In the matched cohort (n=126), greater epileptiform burden, suppression burden and beta variability were associated with 4.6 times higher PTE1 risk based on multivariable logistic regression analysis (area under the receiver operating characteristic curve, AUC (95% CI) 0.69 (0.60 to 0.78)). Among 116 (92%) patients with available CT reports, adding quantitative electroencephalography features to a combined mechanism and CT model improved performance (AUC (95% CI), 0.71 (0.61 to 0.80) vs 0.61 (0.51 to 0.72)). CONCLUSIONS: Epileptiform and spectral characteristics enhance covariates identified on TBI admission and CT abnormalities in PTE1 prediction. Future trials should incorporate quantitative electroencephalography features to validate this enhancement of PTE risk stratification models.


Assuntos
Lesões Encefálicas Traumáticas , Epilepsia Pós-Traumática , Humanos , Epilepsia Pós-Traumática/diagnóstico , Epilepsia Pós-Traumática/etiologia , Estudos Retrospectivos , Estudos de Casos e Controles , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/diagnóstico , Eletroencefalografia/efeitos adversos
14.
J Chin Med Assoc ; 86(2): 240-245, 2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-36346207

RESUMO

BACKGROUND: Reporting the findings from radiologic images is an important method for radiologists to communicate with referring physicians. The purpose of this study was to evaluate the effectiveness of the recommendations for additional imaging (RAIs) after abdominal computed tomography (CT) studies for abdominal magnetic resonance (MR) imaging. METHODS: The institutional review board approved this retrospective study, which includes data collected from the radiology information system (RIS) database of a tertiary medical referral center. Associations between abdominal CT and subsequent abdominal MR were recorded. The effectiveness of RAIs in an abdominal report was determined. The influence of the wording and the location of the RAIs were also analyzed. RESULTS: The presence of RAIs in an abdominal CT report for an abdominal MR examination was more likely to result in a subsequent MR examination within 120 days (36.7% vs. 4.0%). RAIs were also associated with a reduction in the time interval between the CT and MR examinations (29.0 days vs. 39.0 days). The most effective recommendations included wording that advocated for further evaluation and were mentioned in both the context and conclusion of the report. CONCLUSION: RAIs have a significant influence on clinical decisions. Radiologists should be aware of the power of RAIs and be prudent and conscientious when making recommendations in radiology reports.


Assuntos
Radiologia , Tomografia Computadorizada por Raios X , Estudos Retrospectivos , Abdome/diagnóstico por imagem , Imageamento por Ressonância Magnética
15.
Hemasphere ; 6(10): e785, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36204688

RESUMO

Infant acute lymphoblastic leukemia (ALL) with KMT2A-gene rearrangements (KMT2A-r) have few mutations and a poor prognosis. To uncover mutations that are below the detection of standard next-generation sequencing (NGS), a combination of targeted duplex sequencing and NGS was applied on 20 infants and 7 children with KMT2A-r ALL, 5 longitudinal and 6 paired relapse samples. Of identified nonsynonymous mutations, 87 had been previously implicated in cancer and targeted genes recurrently altered in KMT2A-r leukemia and included mutations in KRAS, NRAS, FLT3, TP53, PIK3CA, PAX5, PIK3R1, and PTPN11, with infants having fewer such mutations. Of identified cancer-associated mutations, 62% were below the resolution of standard NGS. Only 33 of 87 mutations exceeded 2% of cellular prevalence and most-targeted PI3K/RAS genes (31/33) and typically KRAS/NRAS. Five patients only had low-frequency PI3K/RAS mutations without a higher-frequency signaling mutation. Further, drug-resistant clones with FLT3 D835H or NRAS G13D/G12S mutations that comprised only 0.06% to 0.34% of diagnostic cells, expanded at relapse. Finally, in longitudinal samples, the relapse clone persisted as a minor subclone from diagnosis and through treatment before expanding during the last month of disease. Together, we demonstrate that infant and childhood KMT2A-r ALL harbor low-frequency cancer-associated mutations, implying a vast subclonal genetic landscape.

16.
Fish Shellfish Immunol ; 126: 271-282, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35609762

RESUMO

Peritrophins are peritrophic membrane (PM) proteins that can interact with chitin fibers via chitin-binding domains. Peritrophins have essential roles in providing porosity and strength to the PM that lines the shrimp midgut. Acute hepatopancreatic necrosis disease (AHPND), caused by strains of V. parahaemolyticus, is known to initially colonize the shrimp stomach and simultaneously disrupt its structural barriers (e.g., cuticle or epithelial tissues) to reach the hepatopancreas. Although stomach and hepatopancreas were identified as target tissues involved in AHPND pathogenesis, our results indicated that peritrophin in peritrophic membrane has a crucial role in determining not only colonization of AHPND-causing bacteria but also their tissue distribution. As the interaction between LvPeritrophin (LvPT) and WSSV (white spot syndrome virus) is not well understood, we noted that LvPT expression was upregulated in shrimp stomach challenged with either WSSV or AHPND. In an in vitro pathogen binding assay, there was strong binding of recombinant LvPT WSSV and AHPND-causing V. parahaemolyticus, and various bacteria. Furthermore, dsRNA-mediated LvPT silencing inhibited WSSV gene expression and viral genome replication. However, downregulation of LvPT gene expression increased copies of AHPND-causing bacteria in shrimp digestive tract, and facilitated bacterial colonization in stomach. In conclusion, we speculated that LvPT might regulate bacterial colonization during AHPND, whereas in WSSV infection, LvPT silencing favored the host. Although recombinant LvPT had strong binding with WSSV, the precise role of LvPT in WSSV infection needs further investigation. These findings increased our understanding of host-pathogen interactions in AHPND and WSSV infection that can be applied in shrimp aquaculture for developing effective antibacterial and antiviral strategies.


Assuntos
Penaeidae , Vibrio parahaemolyticus , Vírus da Síndrome da Mancha Branca 1 , Animais , Quitina/metabolismo , Hepatopâncreas/metabolismo , Interações Hospedeiro-Patógeno , Penaeidae/microbiologia , Vibrio parahaemolyticus/fisiologia , Vírus da Síndrome da Mancha Branca 1/fisiologia
17.
J Ethnopharmacol ; 293: 115272, 2022 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-35405251

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Dandelion (Taraxacum officinale Weber ex F. H. Wigg.), as a garden weed grown globally, has long been consumed as a therapeutic herb. Its folkloric uses include treatments of digestive disorders (dyspepsia, anorexia, stomach disorders, gastritis and enteritis) and associate complex ailments involving uterine, liver and lung disorders. AIM OF THE STUDY: The present study aims to critically assess the current state of research and summarize the potential roles of dandelion and its constituents in gastrointestinal (GI) -protective actions. A focus is placed on the reported bioactive components, pharmacological activities and modes of action (including molecular mechanisms and interactions among bioactive substances) of dandelion products/preparations and derived active constituents related to GI protection. MATERIALS AND METHODS: The available information published prior to August 2021 was reviewed via SciFinder, Web of Science, Google Scholar, PubMed, Elsevier, Wiley On-line Library, and The Plant List. The search was based on the ethnomedical remedies, pharmacological activities, bioactive compounds of dandelion for GI protection, as well as the interactions of the components in dandelion with the gut microbiota or biological regulators, and with other ingested bioactive compounds. The key search words were "Taraxacum" and "dandelion". RESULTS: T. coreanum Nakai, T. mongolicum and T. officinale are the most commonly used species for folkloric uses, with the whole plant, leaves and root of dandelion being used more frequently. GI-protective substances of dandelion include taraxasterol, taraxerol, caffeic acid, chicoric acid, chlorogenic acid, luteolin and its glucosides, polysaccharides, inulin, and ß-sitosterol. Dandelion products and derived constituents exhibit pharmacological effects against GI disorders, mainly including dyspepsia, gastroesophageal reflux disease, gastritis, small intestinal ulcer, ulcerative colitis, liver diseases, gallstones, acute pancreatitis, and GI malignancy. The underlying molecular mechanisms may include immuno-inflammatory mechanisms, apoptosis mechanism, autophagy mechanism, and cholinergic mechanism, although interactions of dandelion's constituents with GI health-related biological entities (e.g., GI microbiota and associated biological modulators) or other ingested bioactive compounds shouldn't be ignored. CONCLUSION: The review reveals some in vivo and in vitro studies on the potential of dandelion derived products as complementary and alternative medicines/therapeutics against GI disorders. The whole herb may alleviate some symptoms related GI immuno-inflammatory basing on the abundant anti-inflammatory and anti-oxide active substances. Dandelion root could be a nontoxic and effective anticancer alternative, owing to its abundant terpenoids and polysaccharides. However, research related to GI protective dandelion-derived products remains limited. Besides the need of identifying bioactive compounds/complexes in various dandelion species, more clinical studies are also required on the metabolism, bioavailability and safety of these substances to support their applications in food, medicine and pharmaceuticals.


Assuntos
Dispepsia , Essências Florais , Gastrite , Pancreatite , Taraxacum , Doença Aguda , Dispepsia/tratamento farmacológico , Gastrite/tratamento farmacológico , Humanos , Pancreatite/tratamento farmacológico , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/uso terapêutico , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico
18.
Chemosphere ; 300: 134484, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35395258

RESUMO

In this study, the Ni(OH)2/CuO heterostructured photocatalysts have been prepared via microwave (MW) hydrothermal method. The results indicate that the Ni(OH)2/CuO heterostructured composite exhibits a strong absorption in the UV and Vis regions. The construction of the heterojunction also improves the photogenerated carrier transport and inhibits the electron-hole separation due to the enhanced absorbance and the well alignment of the energy band at the Ni(OH)2/CuO interface. The photocatalytic capability of the heterostructured composites with different Ni(OH)2/CuO molar ratios is evaluated by the photodegradation of methylene blue under visible light illumination. The results reveal that the Ni(OH)2/CuO (1:1) heterostructures show the best photocatalytic efficiency, which is 2.18 and 6.13 times higher than that of pure Ni(OH)2 and CuO, respectively. Besides, the Ni(OH)2/CuO composites also reveal remarkable biocompatibility and strong photocatalytic activity in the degradation of antibiotics such as ciprofloxacin (CIP) and tetracycline (TC) and inactivation of Escherichia coli (E. coli).


Assuntos
Poluentes Ambientais , Antibacterianos , Catálise , Cobre/química , Escherichia coli
19.
Biotechnol Adv ; 55: 107914, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35085761

RESUMO

Global challenges require novel solutions. Microbial nanotechnology has the potential to offer an eco-friendly approach for advancing the pharmaceutical, food, environment and agriculture sectors. This review summarizes recent developments in the synthesis and applications of bionanomaterials created by intracellular and/or extracellular biosynthesis processes involving various microorganisms (e.g. bacterium, fungus, yeast, virus and microalga) and/or derived metabolites/secreted substances. Insights into the mechanisms underlying the synthesis of microbial-assisted nanomaterials, and the superiority of these 'green' processes and resulting microbiotic nanomaterials in various applications, are provided. Such knowledge supports the development of microfactories for the biosynthesis of diverse nanomaterials at scale under controlled conditions. This review highlights current hurdles and bottleneck issues, whilst demonstrating the need to manipulate microorganisms at both the genomic and proteomic levels, thereby tailoring the properties of the derived bionanomaterials for target applications. For many envisaged applications, toxicological and ecotoxicological studies on synthesized nanomaterials are needed, along with the establishment of suitable regulatory frameworks.


Assuntos
Nanoestruturas , Proteômica , Bactérias/genética , Fungos/genética , Nanotecnologia/métodos
20.
Food Chem ; 370: 131265, 2022 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-34788950

RESUMO

Yellowing is a critical issue that reduces quality and commodity value of rice. This article presents an overview on rice yellowing and the mechanism of rice yellowing was addressed as the emphasis. The change of physicochemical and nutritive properties in yellowed rice depends on the exposure temperature and time, as well as rice cultivar. The temperature and moisture on rice yellowing were dominant. There is no consensus on the relationship between microorganisms and rice yellowing. The occurrence of yellowing is mainly associated with heat stress induced by heaping heat or respiration of grain, and the yellowing is the collective result of primary and secondary metabolism. The upregulation of flavonoids is the direct cause of rice yellowing, which can be used as metabolic markers of rice yellowing. The Maillard reaction also contributes to yellowing during storage. Aeration and cooling are recommended to lessen the occurring of rice yellowing during commercial storage.


Assuntos
Oryza , Temperatura Baixa , Flavonoides , Metabolismo Secundário
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