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1.
Infect Drug Resist ; 17: 4113-4123, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39319038

RESUMO

Purpose: Staphylococcus aureus, including methicillin-resistant Staphylococcus aureus (MRSA) strain, can become resistant to all classes of clinically available antibiotics and causes skin infections and severe infections in the lungs, heart, and bloodstream. The study aimed to evaluate antimicrobial susceptibility patterns and MRSA exhibiting multidrug resistance obtained through a microbiological culture of clinical specimens at Bac Ninh Provincial General Hospital in Bac Ninh Province, Vietnam. Methods: We employed a cross-sectional analysis at Bac Ninh Provincial General Hospital in Vietnam. 15,232 clinical samples from inpatients were examined. S. aureus isolates were identified using established protocols and tested for MRSA and antibiotic susceptibility. Data was analyzed using R software, with statistical calculations to assess associations between variables. Results: Staphylococcus aureus was isolated from 417 samples (2.7%), with 77.2% being MRSA and 22.8% methicillin-susceptible Staphylococcus aureus (MSSA). Significant sources of MRSA were wounds (64.6%) and the surgical unit (50%) according to sample types and hospital wards, respectively. S. aureus showed high resistance rates, the highest being azithromycin (83.2%), and was fully susceptible to vancomycin. Among 294 multidrug-resistant (MDR) strains, the prevalence was 82.0% in MRSA and 18.0% in MSSA. Conclusion: The study highlights widespread antimicrobial resistance among MRSA isolates from a provincial hospital in Vietnam, emphasizing the urgent need for antibiotic surveillance, formulation of antibiotic policies, and preventive measures to tackle the increasing prevalence of multidrug-resistant MRSA.

2.
Pathology ; 56(5): 633-642, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38719771

RESUMO

Prostate and breast cancer incidence rates have been on the rise in Japan, emphasising the need for precise histopathological diagnosis to determine patient prognosis and guide treatment decisions. However, existing diagnostic methods face numerous challenges and are susceptible to inconsistencies between observers. To tackle these issues, artificial intelligence (AI) algorithms have been developed to aid in the diagnosis of prostate and breast cancer. This study focuses on validating the performance of two such algorithms, Galen Prostate and Galen Breast, in a Japanese cohort, with a particular focus on the grading accuracy and the ability to differentiate between invasive and non-invasive tumours. The research entailed a retrospective examination of 100 consecutive prostate and 100 consecutive breast biopsy cases obtained from a Japanese institution. Our findings demonstrated that the AI algorithms showed accurate cancer detection, with AUCs of 0.969 and 0.997 for the Galen Prostate and Galen Breast, respectively. The Galen Prostate was able to detect a higher Gleason score in four adenocarcinoma cases and detect a previously unreported cancer. The two algorithms successfully identified relevant pathological features, such as perineural invasions and lymphovascular invasions. Although further improvements are required to accurately differentiate rare cancer subtypes, these findings highlight the potential of these algorithms to enhance the precision and efficiency of prostate and breast cancer diagnosis in Japan. Furthermore, this validation paves the way for broader adoption of these algorithms as decision support tools within the Asian population.


Assuntos
Algoritmos , Inteligência Artificial , Neoplasias da Mama , Gradação de Tumores , Neoplasias da Próstata , Humanos , Estudos Retrospectivos , Masculino , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/patologia , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/patologia , Feminino , Japão , Idoso , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Adulto , Adenocarcinoma/diagnóstico , Adenocarcinoma/patologia , Estudos de Coortes , População do Leste Asiático
3.
Jpn J Infect Dis ; 77(3): 144-154, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38296537

RESUMO

This cross-sectional study investigated the antimicrobial resistance (AMR) patterns of gram-negative pathogens isolated from 4,789 hospitalized patients with lower respiratory tract infections (LRTIs). Of the collected specimens, 1,325 (27.7%) tested positive for gram-negative bacteria. Acinetobacter baumannii (38.6%), Pseudomonas aeruginosa (33.5%), Klebsiella pneumoniae (18.7%), Escherichia coli (5.6%), and Klebsiella aerogenes (3.5%) were the most prevalent isolates. AMR analysis revealed high resistance rates (79.9%-100%) of A. baumannii isolates to multiple classes of antibiotics except amikacin, trimethoprim/sulfamethoxazole, and colistin. P. aeruginosa displayed low resistance to colistin (< 10%) but high resistance to other antibiotics. K. pneumoniae displayed high resistance rates of 90.0%-100.0% to most penicillins, whereas resistance rates were notably lower for colistin (7.1%) and amikacin (16.7%). K. aerogenes exhibited high resistance to various antibiotics and sensitivity to amikacin (95.1%), ampicillin (100.0%), and colistin (100.0%). E. coli isolates exhibited resistance to ampicillin (96.9%) and maximum sensitivity to several antibiotics. Our study identified significant AMR trends and highlighted the prevalence of multidrug-resistant strains (93.6% for K. aerogenes and 69.1%-92.4% for other isolates). These findings emphasize the urgent need for appropriate antibiotic management practices to combat AMR in gram-negative pathogens associated with LRTIs.


Assuntos
Antibacterianos , Farmacorresistência Bacteriana , Bactérias Gram-Negativas , Infecções por Bactérias Gram-Negativas , Hospitais de Ensino , Testes de Sensibilidade Microbiana , Infecções Respiratórias , Humanos , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/isolamento & purificação , Antibacterianos/farmacologia , Infecções Respiratórias/microbiologia , Infecções Respiratórias/epidemiologia , Infecções por Bactérias Gram-Negativas/microbiologia , Infecções por Bactérias Gram-Negativas/epidemiologia , Pessoa de Meia-Idade , Vietnã/epidemiologia , Estudos Transversais , Adulto , Masculino , Feminino , Idoso , Adulto Jovem , Adolescente , Criança , Idoso de 80 Anos ou mais , Pré-Escolar , Lactente
4.
Chinese Pharmacological Bulletin ; (12): 545-551, 2024.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1013581

RESUMO

Aim To investigate the effects of 2-dode-cyl-6-methoxycyclohexa-2 , 5-diene-l, 4-dione ( DM-DD) on resisting hepatic fibrosis induced by carbon tetrachloride ( CC14 ) in rats and the underlying mechanisms , with a specific focus on the TGF-pi/Smads signaling pathway. Methods The hepatic fibrosis model was replicated using 50% CC14. Various parameters, including levels of aspartate transferase ( AST) , ala-nine transferase ( ALT ) , albumin/globulin ( A/G ) , total protein (TP) , total bilirubin (T-BIL) , hyaluron-ic acid ( HA ) , laminin ( LN ) , collagen type Ж ( Col Ж) , and collagen type IV(ColIV) in the blood, were measured. Liver tissue lesions and fiber formation were observed using HE and Masson staining. The expression levels of a smooth muscle actin (a-SMA) , collagen type I ( Col I ) , transformed growth factor (TGF-pi), Smad2, and Smad7 proteins were assessed using immunohistochemistry. a-SMA, Coll, TGF-pi, and Smad7 mRNA levels in liver tissue were measured by RT-PCR. Additionally, the expression levels of TGF-pi, Smad4, and Smad7 proteins in liver tissue were determined by Western blot. Results In comparison to the normal control group, the model group exhibited significantly elevated levels of AST, ALT, TP, T-BIL, HA, LN, Col Ш and Col IV in serum. But A/G level notably decreased. Successful modeling was confirmed by the presence of extensive fiber formations observed through HE and Massonstaining in liver tissue. The DMDD administration group demonstrated a notable decrease levels of AST, ALT, TP, T-BIL, HA, LN, Col III, and CollV, but A/G was significantly elevated when compared to the model group. Furthermore, a-SMA, Coll, TGF-f31, Smad2 and Smad4 mRNA and protein levels in the DMDD administration group were significantly reduced, while Smad7 significantly declined. HE and Masson staining results reflected a marked reduction in fibrous hyper-plasia. Conclusion DMDD exhibits a protective effect against CCl4-induced hepatic fibrosis, and its mechanism appears to be associated with the TGF-fJl/ Smads signaling pathway.

5.
Int J Mol Sci ; 24(18)2023 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-37762311

RESUMO

Antibiotic resistance has emerged as one of the most significant threats to global public health. Plasmids, which are highly efficient self-replicating genetic vehicles, play a critical role in the dissemination of drug-resistant genes. Previous studies have mainly focused on drug-resistant genes only, often neglecting the complete functional role of multidrug-resistant (MDR) plasmids in bacteria. In this study, we conducted a comprehensive investigation of the transcriptomes and proteomes of Escherichia coli J53 transconjugants harboring six major MDR plasmids of different incompatibility (Inc) groups, which were clinically isolated from patients. The RNA-seq analysis revealed that MDR plasmids influenced the gene expression in the bacterial host, in particular, the genes related to metabolic pathways. A proteomic analysis demonstrated the plasmid-induced regulation of several metabolic pathways including anaerobic respiration and the utilization of various carbon sources such as serine, threonine, sialic acid, and galactarate. These findings suggested that MDR plasmids confer a growth advantage to bacterial hosts in the gut, leading to the expansion of plasmid-carrying bacteria over competitors without plasmids. Moreover, this study provided insights into the versatility of prevalent MDR plasmids in moderating the cellular gene network of bacteria, which could potentially be utilized in therapeutics development for bacteria carrying MDR plasmids.


Assuntos
Proteoma , Transcriptoma , Humanos , Proteoma/genética , Proteômica , Escherichia coli/genética , Plasmídeos/genética
6.
NPJ Precis Oncol ; 7(1): 77, 2023 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-37582946

RESUMO

Pathologic examination of prostate biopsies is time consuming due to the large number of slides per case. In this retrospective study, we validate a deep learning-based classifier for prostate cancer (PCA) detection and Gleason grading (AI tool) in biopsy samples. Five external cohorts of patients with multifocal prostate biopsy were analyzed from high-volume pathology institutes. A total of 5922 H&E sections representing 7473 biopsy cores from 423 patient cases (digitized using three scanners) were assessed concerning tumor detection. Two tumor-bearing datasets (core n = 227 and 159) were graded by an international group of pathologists including expert urologic pathologists (n = 11) to validate the Gleason grading classifier. The sensitivity, specificity, and NPV for the detection of tumor-bearing biopsies was in a range of 0.971-1.000, 0.875-0.976, and 0.988-1.000, respectively, across the different test cohorts. In several biopsy slides tumor tissue was correctly detected by the AI tool that was initially missed by pathologists. Most false positive misclassifications represented lesions suspicious for carcinoma or cancer mimickers. The quadratically weighted kappa levels for Gleason grading agreement for single pathologists was 0.62-0.80 (0.77 for AI tool) and 0.64-0.76 (0.72 for AI tool) for the two grading datasets, respectively. In cases where consensus for grading was reached among pathologists, kappa levels for AI tool were 0.903 and 0.855. The PCA detection classifier showed high accuracy for PCA detection in biopsy cases during external validation, independent of the institute and scanner used. High levels of agreement for Gleason grading were indistinguishable between experienced genitourinary pathologists and the AI tool.

7.
J Food Sci Technol ; 60(5): 1521-1529, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37033307

RESUMO

Bitter gourd extract (BGE) is rich in antioxidants and anti-diabetic components that promote good human health; however, its bitter taste makes it challenging to use in food. In this study, the effect of carboxymethyl cellulose and ß-cyclodextrin (ß-CD) on the bitterness and properties of BGE were investigated. The bitterness intensity was evaluated by the trained sensory panel, and the physicochemical properties were also determined, including viscosity, total saponin, polyphenol content, antioxidant capacity, and α-amylase inhibition activity. It was found that the bitterness of BGE with 0.75%, w/v ß-cyclodextrin decreased significantly by more than 90%. Additionally, FTIR, 1 H-NMR, and thermogravimetric analysis of BGE supplemented with ß-CD confirmed the formation of a complex between ß-CD and components of BGE. The findings of the current study also reveal that debittering agents did not inhibit the bioactivities of BGE.

8.
Int J Med Microbiol ; 313(1): 151573, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36634604

RESUMO

Uropathogenic Escherichia coli (UPEC) are causative agent that causes urinary tract infections (UTIs) and the recent emergence of multidrug resistance (MDR) of UPEC increases the burden on the community. Recent studies of bacterial outer membrane vesicles (OMV) identified various factors including proteins, nucleic acids, and small molecules which provided inter-cellular communication within the bacterial population. However, the components of UPEC-specific OMVs and their functional role remain unclear. Here, we systematically determined the proteomes of UPEC-OMVs and identified the specific components that provide functions to the recipient bacteria. Based on the functional network of OMVs' proteomes, a group of signaling peptides was found in all OMVs which provide communication among bacteria. Moreover, we demonstrated that treatment with UPEC-OMVs affected the motility and biofilm formation of the recipient bacteria, and further identified aromatic amino acid (AAA) biosynthesis proteins as the key factors to provide their movement.


Assuntos
Infecções por Escherichia coli , Proteínas de Escherichia coli , Infecções Urinárias , Escherichia coli Uropatogênica , Humanos , Proteínas de Escherichia coli/metabolismo , Proteoma/metabolismo , Infecções Urinárias/microbiologia , Infecções por Escherichia coli/microbiologia
9.
Sensors (Basel) ; 22(17)2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36081066

RESUMO

Machine learning (ML) has been widely used worldwide to develop crop yield forecasting models. However, it is still challenging to identify the most critical features from a dataset. Although either feature selection (FS) or feature extraction (FX) techniques have been employed, no research compares their performances and, more importantly, the benefits of combining both methods. Therefore, this paper proposes a framework that uses non-feature reduction (All-F) as a baseline to investigate the performance of FS, FX, and a combination of both (FSX). The case study employs the vegetation condition index (VCI)/temperature condition index (TCI) to develop 21 rice yield forecasting models for eight sub-regions in Vietnam based on ML methods, namely linear, support vector machine (SVM), decision tree (Tree), artificial neural network (ANN), and Ensemble. The results reveal that FSX takes full advantage of the FS and FX, leading FSX-based models to perform the best in 18 out of 21 models, while 2 (1) for FS-based (FX-based) models. These FXS-, FS-, and FX-based models improve All-F-based models at an average level of 21% and up to 60% in terms of RMSE. Furthermore, 21 of the best models are developed based on Ensemble (13 models), Tree (6 models), linear (1 model), and ANN (1 model). These findings highlight the significant role of FS, FX, and specially FSX coupled with a wide range of ML algorithms (especially Ensemble) for enhancing the accuracy of predicting crop yield.


Assuntos
Aprendizado de Máquina , Redes Neurais de Computação , Algoritmos , Previsões , Máquina de Vetores de Suporte
10.
Histopathology ; 81(6): 758-769, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35989443

RESUMO

AIMS: The reporting of tumour cellularity in cancer samples has become a mandatory task for pathologists. However, the estimation of tumour cellularity is often inaccurate. Therefore, we propose a collaborative workflow between pathologists and artificial intelligence (AI) models to evaluate tumour cellularity in lung cancer samples and propose a protocol to apply it to routine practice. METHODS AND RESULTS: We developed a quantitative model of lung adenocarcinoma that was validated and tested on 50 cases, and a collaborative workflow where pathologists could access the AI results and adjust their original tumour cellularity scores (adjusted-score) that we tested on 151 cases. The adjusted-score was validated by comparing them with a ground truth established by manual annotation of haematoxylin and eosin slides with reference to immunostains with thyroid transcription factor-1 and napsin A. For training, validation, testing the AI and testing the collaborative workflow, we used 40, 10, 50 and 151 whole slide images of lung adenocarcinoma, respectively. The sensitivity and specificity of tumour segmentation were 97 and 87%, respectively, and the accuracy of nuclei recognition was 99%. One pathologist's visually estimated scores were compared to the adjusted-score, and the pathologist's scores were altered in 87% of cases. Comparison with the ground truth revealed that the adjusted-score was more precise than the pathologists' scores (P < 0.05). CONCLUSION: We proposed a collaborative workflow between AI and pathologists as a model to improve daily practice and enhance the prediction of tumour cellularity for genetic tests.


Assuntos
Adenocarcinoma de Pulmão , Aprendizado Profundo , Neoplasias Pulmonares , Humanos , Patologistas , Inteligência Artificial , Fluxo de Trabalho , Adenocarcinoma de Pulmão/diagnóstico , Neoplasias Pulmonares/diagnóstico
11.
Toxicol Res ; 38(3): 355-364, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35874500

RESUMO

3-Caffeoyl-4-dicaffeoylquinic acid (CDCQ) is a natural chlorogenic acid isolated from Salicornia herbacea that protects against oxidative stress, inflammation, and cancer. Nitric oxide (NO) plays a physiologically beneficial role in the cardiovascular system, including vasodilation, protection of endothelial cell function, and anti-inflammation. However, the effect of CDCQ on NO production and eNOS phosphorylation in endothelial cells is unclear. We investigated the effect of CDCQ on eNOS phosphorylation and NO production in human endothelial cells, and the underlying signaling pathway. CDCQ significantly increased NO production and the phosphorylation of eNOS at Ser1177. Additionally, CDCQ induced phosphorylation of PKA, CaMKII, CaMKKß, and AMPK. Interestingly, CDCQ increased the intracellular Ca2+ level, and L-type Ca2+ channel (LTCC) blockade significantly attenuated CDCQ-induced eNOS activity and NO production by inhibiting PKA, CaMKII, CaMKKß, and AMPK phosphorylation. These results suggest that CDCQ increased eNOS phosphorylation and NO production by Ca2+-dependent phosphorylation of PKA, CaMKII, CaMKKß, and AMPK. Our findings provide evidence that CDCQ plays a pivotal role in the activity of eNOS and NO production, which is involved in the protection of endothelial dysfunction.

12.
PLoS One ; 17(5): e0263546, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35507596

RESUMO

Model organisms mimicking the pathogenesis of human diseases are useful for identifying pathogenic mechanisms and testing therapeutic efficacy of compounds targeting them. Models of Alzheimer's disease (AD) and related dementias (ADRD) aim to reproduce the brain pathology associated with these neurodegenerative disorders. Transgenic models, which involve random insertion of disease-causing genes under the control of artificial promoters, are efficient means of doing so. There are confounding factors associated with transgenic approaches, however, including target gene overexpression, dysregulation of endogenous gene expression at transgenes' integration sites, and limitations in mimicking loss-of-function mechanisms. Furthermore, the choice of species is important, and there are anatomical, physiological, and cognitive reasons for favoring the rat over the mouse, which has been the standard for models of neurodegeneration and dementia. We report an initial assessment of the spatial learning, reversal, and sequencing task capabilities of knock-in (KI) Long-Evans rats with humanizing mutations in the Aß-coding region of App, which encodes amyloid precursor protein (Apph/h rats), using the IntelliCage, an automated operant social home cage system, at 6-8 weeks of age, then again at 4-5 months of age. These rats were previously generated as control organisms for studies on neurodegeneration involving other knock-in rat models from our lab. Apph/h rats of either sex can acquire place learning and reversal tasks. They can also acquire a diagonal sequencing task by 6-8 weeks of age, but not a more advanced serial reversal task involving alternating diagonals, even by 4-5 months of age. Thus, longitudinal behavioral analysis with the IntelliCage system can be useful to determine, in follow-up studies, whether KI rat models of Familial AD (FAD), sporadic late onset AD (LOAD), and of ADRD develop aging-dependent learning and memory deficits.


Assuntos
Doença de Alzheimer , Aplicativos Móveis , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Modelos Animais de Doenças , Camundongos Transgênicos , Mutação , Ratos , Ratos Long-Evans , Reversão de Aprendizagem
13.
Sensors (Basel) ; 22(3)2022 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-35161461

RESUMO

Accurate crop yield forecasting is essential in the food industry's decision-making process, where vegetation condition index (VCI) and thermal condition index (TCI) coupled with machine learning (ML) algorithms play crucial roles. The drawback, however, is that a one-fits-all prediction model is often employed over an entire region without considering subregional VCI and TCI's spatial variability resulting from environmental and climatic factors. Furthermore, when using nonlinear ML, redundant VCI/TCI data present additional challenges that adversely affect the models' output. This study proposes a framework that (i) employs higher-order spatial independent component analysis (sICA), and (ii), exploits a combination of the principal component analysis (PCA) and ML (i.e., PCA-ML combination) to deal with the two challenges in order to enhance crop yield prediction accuracy. The proposed framework consolidates common VCI/TCI spatial variability into their respective subregions, using Vietnam as an example. Compared to the one-fits-all approach, subregional rice yield forecasting models over Vietnam improved by an average level of 20% up to 60%. PCA-ML combination outperformed ML-only by an average of 18.5% up to 45%. The framework generates rice yield predictions 1 to 2 months ahead of the harvest with an average of 5% error, displaying its reliability.


Assuntos
Aprendizado de Máquina , Oryza , Algoritmos , Reprodutibilidade dos Testes
14.
Am J Phys Med Rehabil ; 101(4): 400-404, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-34657086

RESUMO

ABSTRACT: Many studies suggest a brief statistical benefit on survival and quality of life by using nasal noninvasive ventilation for patients with amyotrophic lateral sclerosis and other neuromuscular conditions. Indeed, nasal noninvasive ventilation has become synonymous with continuous positive airway pressure and lo-span bilevel positive airway pressure. Nasal noninvasive ventilation, however, may not normalize CO2 levels and continuous positive airway pressure and O2 exacerbate hypercapnia and often lead to CO2 narcosis, intubation, and ultimately tracheostomy or palliative care death. However, a third option can be to offer up to continuous noninvasive ventilatory support and extubation to it. Noninvasive ventilatory support can be effective for full, definitive ventilatory support, even for people with no measurable vital capacity, and has maintained classic amyotrophic lateral sclerosis patients for up to 12 yrs without resort to tracheotomies. Nineteen centers have reported 335 amyotrophic lateral sclerosis patients using continuous noninvasive ventilatory support instead of tracheostomy mechanical ventilation for an average of 14 mos (6 mos to 14 yrs). The noninvasive ventilatory support must also be used in conjunction with mechanical insufflation-exsufflation to clear airway debris and normalize or renormalize ambient air oxyhemoglobin saturation, both to avoid intubation and to facilitate extubation. People with amyotrophic lateral sclerosis satisfying specific criteria, even when continuously dependent on tracheostomy mechanical ventilation, can be decannulated and placed on continuous noninvasive ventilatory support with mechanical insufflation-exsufflation.


Assuntos
Esclerose Lateral Amiotrófica , Ventilação não Invasiva , Insuficiência Respiratória , Esclerose Lateral Amiotrófica/terapia , Dióxido de Carbono , Humanos , Hipercapnia/etiologia , Hipercapnia/terapia , Qualidade de Vida , Respiração Artificial , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/terapia
15.
Nat Commun ; 12(1): 6655, 2021 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-34789716

RESUMO

Small-cell lung cancer (SCLC) is speculated to harbor complex genomic intratumor heterogeneity (ITH) associated with high recurrence rate and suboptimal response to immunotherapy. Here, using multi-region whole exome/T cell receptor (TCR) sequencing as well as immunohistochemistry, we reveal a rather homogeneous mutational landscape but extremely cold and heterogeneous TCR repertoire in limited-stage SCLC tumors (LS-SCLCs). Compared to localized non-small cell lung cancers, LS-SCLCs have similar predicted neoantigen burden and genomic ITH, but significantly colder and more heterogeneous TCR repertoire associated with higher chromosomal copy number aberration (CNA) burden. Furthermore, copy number loss of IFN-γ pathway genes is frequently observed and positively correlates with CNA burden. Higher mutational burden, higher T cell infiltration and positive PD-L1 expression are associated with longer overall survival (OS), while higher CNA burden is associated with shorter OS in patients with LS-SCLC.


Assuntos
Neoplasias Pulmonares/genética , Carcinoma de Pequenas Células do Pulmão/genética , Linfócitos T/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Variações do Número de Cópias de DNA , Feminino , Heterogeneidade Genética , Antígenos HLA/genética , Humanos , Interferon gama/imunologia , Perda de Heterozigosidade , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Mutação , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos de Linfócitos T/imunologia , Transdução de Sinais/genética , Carcinoma de Pequenas Células do Pulmão/imunologia , Carcinoma de Pequenas Células do Pulmão/patologia , Análise de Sobrevida , Sequenciamento do Exoma
16.
Nat Commun ; 12(1): 2722, 2021 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-33976164

RESUMO

The mechanism by which anti-cancer immunity shapes early carcinogenesis of lung adenocarcinoma (ADC) is unknown. In this study, we characterize the immune contexture of invasive lung ADC and its precursors by transcriptomic immune profiling, T cell receptor (TCR) sequencing and multiplex immunofluorescence (mIF). Our results demonstrate that anti-tumor immunity evolved as a continuum from lung preneoplasia, to preinvasive ADC, minimally-invasive ADC and frankly invasive lung ADC with a gradually less effective and more intensively regulated immune response including down-regulation of immune-activation pathways, up-regulation of immunosuppressive pathways, lower infiltration of cytotoxic T cells (CTLs) and anti-tumor helper T cells (Th), higher infiltration of regulatory T cells (Tregs), decreased T cell clonality, and lower frequencies of top T cell clones in later-stages. Driver mutations, chromosomal copy number aberrations (CNAs) and aberrant DNA methylation may collectively impinge host immune responses and facilitate immune evasion, promoting the outgrowth of fit subclones in preneoplasia into dominant clones in invasive ADC.


Assuntos
Adenocarcinoma in Situ/genética , Adenocarcinoma de Pulmão/genética , Carcinogênese/genética , Neoplasias Pulmonares/genética , Proteínas de Neoplasias/genética , Lesões Pré-Cancerosas/genética , Transcriptoma , Adenocarcinoma in Situ/imunologia , Adenocarcinoma in Situ/patologia , Adenocarcinoma de Pulmão/imunologia , Adenocarcinoma de Pulmão/patologia , Carcinogênese/imunologia , Carcinogênese/patologia , Aberrações Cromossômicas , Células Clonais , Variações do Número de Cópias de DNA , Metilação de DNA , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Imunidade Inata , Pulmão/imunologia , Pulmão/metabolismo , Pulmão/patologia , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Proteínas de Neoplasias/imunologia , Lesões Pré-Cancerosas/imunologia , Lesões Pré-Cancerosas/patologia , Transdução de Sinais , Linfócitos T Citotóxicos/imunologia , Linfócitos T Citotóxicos/patologia , Linfócitos T Auxiliares-Indutores/imunologia , Linfócitos T Auxiliares-Indutores/patologia , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/patologia , Evasão Tumoral/genética , Evasão Tumoral/imunologia , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia
17.
Carbohydr Polym ; 264: 118012, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-33910716

RESUMO

Transparent-wood (TW) is an emerging research topic that can be applied to biobased products. However, it is necessary to fill pores in TW with natural substances to prepare all-biobased TW. This paper reports an all-biobased TW by infiltrating cellulose nanofiber (CNF) and chitosan (CTS) suspensions into the bleached wood. CNF was isolated by combining the chemical and physical methods, and CTS was dissolved in acetic acid, and they were infiltrated into the pores of the bleached Fir veneer wood using a vacuum jar. The CNF and chitosan effects on the mechanical properties of the TW were studied, and the morphologies, crystallinity index, water contact angle, antioxidant, thermal degradation, and UV-shielding properties were investigated. The prepared TW showed 80 % total transmittance and 30-60 % haze, suitable for solar cell application. The all-biobased TW showed good thermal stability up to 315 °C and excellent UV shielding property for UV-B and UV-C. The antioxidant property of the CTS-TW significantly increased as compared to the original wood. The CNF-TW showed considerable tensile strength and yield strength of more than 200 % improved from the original wood. The potential for environment-friendly packaging applications was demonstrated by making a bag, medicine packaging, and straw for a drink.


Assuntos
Celulose/química , Quitosana/química , Nanofibras/química , Embalagem de Produtos/métodos , Madeira/química , Abies/química , Antioxidantes/química , Clareadores/química , Meio Ambiente , Embalagem de Alimentos/métodos , Humanos , Temperatura , Resistência à Tração , Raios Ultravioleta , Vácuo
18.
Nat Commun ; 12(1): 687, 2021 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-33514726

RESUMO

The evolution of DNA methylome and methylation intra-tumor heterogeneity (ITH) during early carcinogenesis of lung adenocarcinoma has not been systematically studied. We perform reduced representation bisulfite sequencing of invasive lung adenocarcinoma and its precursors, atypical adenomatous hyperplasia, adenocarcinoma in situ and minimally invasive adenocarcinoma. We observe gradual increase of methylation aberrations and significantly higher level of methylation ITH in later-stage lesions. The phylogenetic patterns inferred from methylation aberrations resemble those based on somatic mutations suggesting parallel methylation and genetic evolution. De-convolution reveal higher ratio of T regulatory cells (Tregs) versus CD8 + T cells in later-stage diseases, implying progressive immunosuppression with neoplastic progression. Furthermore, increased global hypomethylation is associated with higher mutation burden, copy number variation burden and AI burden as well as higher Treg/CD8 ratio, highlighting the potential impact of methylation on chromosomal instability, mutagenesis and tumor immune microenvironment during early carcinogenesis of lung adenocarcinomas.


Assuntos
Adenocarcinoma de Pulmão/genética , Metilação de DNA/genética , Epigenoma/genética , Neoplasias Pulmonares/genética , Lesões Pré-Cancerosas/genética , Adenocarcinoma de Pulmão/mortalidade , Adenocarcinoma de Pulmão/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinogênese/genética , Instabilidade Cromossômica , Variações do Número de Cópias de DNA , Progressão da Doença , Feminino , Heterogeneidade Genética , Humanos , Hiperplasia/genética , Hiperplasia/patologia , Pulmão/patologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Mutagênese , Taxa de Mutação , Lesões Pré-Cancerosas/patologia , Análise de Sobrevida , Microambiente Tumoral/genética
19.
Ann Diagn Pathol ; 51: 151701, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33485052

RESUMO

INTRODUCTION: PD1/PD-L1 pathway targeting therapies are nowadays an established treatment option for patients with NSCLC. We assessed whether PD-L1 expression in NSCLC tumor cells was associated with specific clinical features or overall survival using four different clones. METHODS AND RESULTS: A retrospective study included formalin-fixed paraffin embedded (FFPE) surgical tumors from 482 patients. PD-L1 status was assessed with immunohistochemistry in tumor cells on tissue microarrays using clones 28-8, 22C3, SP263 and SP142. Associations with OS were assessed by Kaplan-Meier and multivariate Cox's regression analysis. Patients' median age: 68 years (39-86); histology: adenocarcinoma (AdCa) 61%, squamous-cell carcinoma (SqCC) 33%, and large cell carcinoma (LCC) 6%; p-stage: IA (46%), IB (30%), IIA (10%), IIB (11,4%), IIIA (1,2%), IIIB - IV (0,4%). PD-L1 positivity (≥1%) in NSCLC for clones 28-8, 22C3, SP263, SP142 was 41.5%, 34.2%, 42.7%, 10.4%, respectively (Pearson Chi-square p < 0.0001). PD-L1 expression was correlated with histology, tumor size and grading. Statistically significant association between PD-L1 expression and OS in NSCLC and Non-AdCa was observed with clone SP142 (log-rank p = 0.045 and p = 0.05, respectively). Statistically significant association between PD-L1 expression and OS in LCC was observed with clones 22C3 (log-rank p = 0.009) and SP263 (log-rank p = 0.050). CONCLUSIONS: Overexpression of the PD-L1 clone SP142 was associated with poor overall survival in NSCLC and Non-AdCa. Clones 22C3 and SP263 were associated with poor prognosis in LCC. PD-L1 status might serve as a prognostic marker in NSCLC.


Assuntos
Antígeno B7-H1/metabolismo , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Células Clonais/metabolismo , Adenocarcinoma/diagnóstico , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Carcinoma de Células Grandes/diagnóstico , Carcinoma de Células Grandes/metabolismo , Carcinoma de Células Grandes/patologia , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/terapia , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Células Clonais/patologia , Feminino , Humanos , Imuno-Histoquímica/métodos , Imunoterapia/métodos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias/métodos , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida
20.
Cells ; 9(12)2020 12 12.
Artigo em Inglês | MEDLINE | ID: mdl-33322687

RESUMO

Epidemiology of hepatocellular carcinoma (HCC) showed a correlation between incidence and geographical-relevant risk factors. This study aims to compare the distributions of cancer stem cells (CSC) in two distant populations in Asia and Europe. We analyzed 52 and 43 selected HCC patients undergoing hepatectomy in Ho Chi Minh City (Vietnam) and Trieste (Italy). Each patient sample consisted of HCC, peri-HCC, and non-tumoral (distal) tissue. Demographic data were recorded together with clinical findings. The protocol for the collection of tissue samples and RNA was standardized in both laboratories and gene expression analysis was performed in a single laboratory with identical PCR conditions. Baseline data showed comparable laboratory findings between the two cohorts. mRNA distribution showed a comparable pattern of all CSC markers analyzed with the expression of CD90 progressively increasing from distal and peri-HCC to be highest in HCC (p < 0.001), confirmed by immunofluorescence data. CD90 mRNA distribution was related to HBV-related HCC and a tumor diameter less than 5 cm. Patients with high tumoral CD90 mRNA had a shorter time (p < 0.05) to tumor recurrence compared to patients with lower CD90. This comparative study showed that CD90 mRNA expressions are comparable between Eastern and Western HCC cases.


Assuntos
Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Células-Tronco Neoplásicas/metabolismo , Antígenos Thy-1/genética , Idoso , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/virologia , Estudos de Coortes , Feminino , Regulação Neoplásica da Expressão Gênica , Hepatite B/complicações , Hepatite B/genética , Humanos , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Células-Tronco Neoplásicas/patologia , Prognóstico , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Antígenos Thy-1/metabolismo
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