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1.
J Anim Sci Biotechnol ; 13(1): 54, 2022 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-35546408

RESUMO

BACKGROUND: Increasing intramuscular fat (IMF) is an important strategy to improve meat quality, but the regulation mechanism of IMF deposition needs to be systematically clarified. RESULTS: A total of 520 chickens from a selected line with improved IMF content and a control line were used to investigate the biochemical mechanism of IMF deposition in chickens. The results showed that the increased IMF would improve the flavor and tenderness quality of chicken meat. IMF content was mainly determined both by measuring triglyceride (TG) and phospholipid (PLIP) in muscle tissue, but only TG content was found to be decisive for IMF deposition. Furthermore, the increase in major fatty acid (FA) components in IMF is mainly derived from TGs (including C16:0, C16:1, C18:1n9c, and C18:2n6c, etc.), and the inhibition of certain very-long-chain FAs would help to IMF/TG deposition. CONCLUSIONS: Our study elucidated the underlying biochemical mechanism of IMF deposition in chicken: Prevalent accumulation of long-chain FAs and inhibitions of medium-chain FAs and very long chain FA would jointly result in the increase of TGs with the FA biosynthesis and cellular uptake ways. Our findings will guide the production of high-quality chicken meat.

2.
Environ Sci Technol ; 2022 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-35584204

RESUMO

Plastic packaging material is widely used to package high-temperature soup food in China, but this combination might lead to increased exposure to phthalates. The health effects and potential biological mechanisms have not been well studied. This study aimed to examine urinary phthalate metabolites and the expression of inflammatory cytokines in the blood before, during, and after a "plastic-packaged high-temperature soup food" dietary intervention in healthy adults. The results showed that compared with those in the preintervention period, urinary creatinine-adjusted levels of monomethyl phthalate (MMP), mono-n-butyl phthalate (MBP), mono-isobutyl phthalate (MIBP), and total phthalate metabolites in the intervention period were significantly higher, with increases of 71.6, 41.8, 38.8, and 29.8% for MMP, MBP, MIBP, and the total phthalate metabolites, respectively. After intervention, the mean levels of IL-1ß, IL-4, and TNF-α mRNA increased by 19.0, 21.5, and 25.0%, respectively, while IL-6 and IFN-γ mRNA decreased by 24.2 and 32.9%, respectively, when compared with the preintervention period. We also observed that several phthalates were associated with the mRNA or protein expression of IL-8, TNF-α, and IL-10. Therefore, consumption of plastic-packaged high-temperature soup food was linked to increased phthalate exposure and might result in significant changes in mRNA expression of several inflammatory cytokines.

3.
J Appl Microbiol ; 2022 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-35543360

RESUMO

AIMS: The altered fecal metabolites and microbiota might be involved in the development of breast cancer. We aimed to investigate the effect of differential metabolites on the proliferative activity of breast cancer cells. METHODS AND RESULTS: We collected fecal samples from 14 breast cancer patients and 14 healthy subjects. Untargeted metabolomics analysis, short-chain fatty acid (SCFA) targeted analysis, and 16S rDNA sequencing was performed. The gut metabolite composition of patients changed significantly. Levels of norvaline, glucuronate, and galacturonate were lower in the Cancer group than in the Control (p < 0.05). 4-Methylcatechol and guaiacol increased (p < 0.05). Acetic acid and butyric acid were lower in the Cancer group than in the Control group (p < 0.05). Isobutyric acid and pentanoic acid were higher in the Cancer group than in the Control (p < 0.05). In the genus, the abundance of Rothia and Actinomyces increased in the Cancer group, compared with the Control group (p < 0.05). The differential microbiotas were clearly associated with differential metabolites but weakly with SCFAs. The abundance of Rothia and Actinomyces was markedly positively correlated with 4-methylcatechol and guaiacol (p < 0.05) and negatively correlated with norvaline (p < 0.05). L-norvaline inhibited the content of Arg-1 in a concentration-dependent manner. Compared with the L-norvaline or doxorubicin hydrochloride (DOX) group, the proliferation abilities of 4T1 cells were the lowest in the L-norvaline combined with DOX (p < 0.05). The apoptosis rate increased (p < 0.05). CONCLUSIONS: Fecal metabolites and microbiota were significantly altered in breast cancer. Levels of differential metabolites (i.e., Norvaline) were significantly correlated with the abundance of differential microbiota. L-norvaline combined with DOX could clearly inhibit the proliferation activity of breast cancer cells. SIGNIFICANCE AND IMPACT OF STUDY: This might provide clues to uncover potential biomarkers for breast cancer diagnosis and treatment.

4.
ACS Sens ; 2022 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-35482555

RESUMO

Low-cost and real-time formaldehyde (HCHO) monitoring is of great importance due to its volatility, extreme toxicity, and ready accessibility. In this work, a low-cost and integrated microelectromechanical system (MEMS) HCHO sensor is developed based on SnO2 multishell hollow microspheres loaded with a bimetallic PdPt (PdPt/SnO2-M) sensitizer. The MEMS sensor exhibits a high sensitivity to HCHO ((Ra/Rg - 1) % = 83.7 @ 1 ppm), ultralow detection limit of 50 ppb, and ultrashort response/recovery time (5.0/7.0 s @ 1 ppm). These excellent HCHO sensing properties are attributed to its unique multishell hollow structure with a large and accessible surface, abundant interfaces, suitable mesoporous structure, and synergistic catalytic effects of bimetal PdPt. The well-defined multishell hollow structure also shows fascinating capacities as good hosts for noble metal loading. Therefore, PdPt bimetallic nanoparticles can be employed to construct a synergistic sensitizer with a high content and good dispersity on this multishell hollow structure, further exhibiting a reduced working temperature and ultrasensitive detection of HCHO. This PdPt/SnO2-M-based MEMS sensor presents a unique and highly sensitive means to detect HCHO, establishing its great promise for potential application in environmental monitoring.

5.
Front Cell Dev Biol ; 10: 790920, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35399509

RESUMO

Background: Stomach adenocarcinoma (STAD) is one of the most common tumors. Tumor mutation burden (TMB) has been linked to immunotherapy response. We wanted to see if there was any link between TMB and cancer prognosis. Methods: The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases were used to obtain mutation data, gene expression profiles, and clinical data. We looked at the differences in gene expression and immune markers between low and high TMB groups, built an immune prognostic model, and created a dynamic nomograph App that may be used in the clinic. Simultaneously, We ran the immunotherapy prediction and model comparison at the same time. Finally, model gene mutation and copy number variation (CNV) were displayed. The cellular functional experiments were used to investigate the potential role of GLP2R in gastric cancer. Results: Firstly, basic mutation information and differences in immune infiltration in STAD are revealed. Secondly, the prognostic model developed by us has good accuracy, and the corresponding dynamic nomograph Apps online and immunotherapy prediction facilitate clinical transformation. Furthermore, GLP2R knockdown significantly inhibited the proliferation, migration of gastric cancer cells in vitro. Conclusion: Our findings imply that TMB plays a significant role in the prognosis of STAD patients from a biological perspective. GLP2R may serve as a potential target for gastric cancer.

6.
Int J Biol Sci ; 18(6): 2639-2651, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35414766

RESUMO

Due to increased drug and radiation tolerance, there is an urgent need to develop novel anticancer agents. In our previous study, we performed a series of structural modifications of ursolic acid (UA), a natural product of pentacyclic triterpenes, and found UA232, a derivative with stronger anti-tumor activity. In vitro experiments showed that UA232 inhibited proliferation, induced G0/G1 arrest, and promoted apoptosis in human breast cancer and cervical cancer cells. Mechanistic studies revealed that UA232 promoted apoptosis and induced protective autophagy via the protein kinase R-like endoplasmic reticulum kinase/activating transcription factor 4/C/EBP homologous protein-mediated endoplasmic reticulum stress. In addition, we also found that UA232 induced lysosomal biogenesis, increased lysosomal membrane permeability, promoted lysosomal protease release, and led to lysosome-dependent cell death. Furthermore, UA232 suppressed tumor growth in a mouse xenograft model. In conclusion, our study revealed that UA232 exerts multiple pharmacological effects against breast and cervical cancers by simultaneously triggering endoplasmic reticulum stress and lysosomal dysfunction. Thus, UA232 may be a promising drug candidate for cancer treatment.


Assuntos
Apoptose , Estresse do Retículo Endoplasmático , Animais , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Lisossomos , Camundongos , Triterpenos
7.
Oral Dis ; 2022 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-35426206

RESUMO

BACKGROUND: Hydrogen sulfide (H2 S) is the most important compound causing oral malodor, and its concentration is thought to be closely correlated with oral microorganism activity. Therefore, clarifying the correlation between oral microbes and metabolites is important. METHODS: This study tested with 16S rRNA gene amplicon and shotgun metagenomic sequencing of oral microorganisms and oral malodor tests. RESULTS: There were different of the microbial taxa between the low and high H2 S groups. And in the high H2 S group, most of the enriched taxa were genera which abundance was correlated with H2 S concentration. Fusobacterium periodonticum and Prevotella nanceiensis were significantly different in coverage breadth and depth and in LPS biosynthesis contributions between the two groups. The contribution of F. periodonticum to sulfur metabolism was significantly different between the two groups, and the relative F. periodonticum abundance was higher in the high H2 S group. CONCLUSIONS: The H2 S content is significantly associated with the oral cavity microorganism composition and abundance. Most microorganisms enriched in people with high H2 S levels are associated with oral diseases such as caries and periodontal diseases.

8.
Hum Brain Mapp ; 2022 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-35388581

RESUMO

Incidence of schizophrenia (SZ) has two predominant peaks, in adolescent and young adult. Early-onset schizophrenia provides an opportunity to explore the neuropathology of SZ early in the disorder and without the confound of antipsychotic mediation. However, it remains unexplored what deficits are shared or differ between adolescent early-onset (EOS) and adult-onset schizophrenia (AOS) patients. Here, based on 529 participants recruited from three independent cohorts, we explored AOS and EOS common and unique co-varying patterns by jointly analyzing three MRI features: fractional amplitude of low-frequency fluctuations (fALFF), gray matter (GM), and functional network connectivity (FNC). Furthermore, a prediction model was built to evaluate whether the common deficits in drug-naive SZ could be replicated in chronic patients. Results demonstrated that (1) both EOS and AOS patients showed decreased fALFF and GM in default mode network, increased fALFF and GM in the sub-cortical network, and aberrant FNC primarily related to middle temporal gyrus; (2) the commonly identified regions in drug-naive SZ correlate with PANSS positive significantly, which can also predict PANSS positive in chronic SZ with longer duration of illness. Collectively, results suggest that multimodal imaging signatures shared by two types of drug-naive SZ are also associated with positive symptom severity in chronic SZ and may be vital for understanding the progressive schizophrenic brain structural and functional deficits.

9.
BMC Genomics ; 23(1): 308, 2022 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-35428174

RESUMO

BACKGROUND: Chicken intramuscular fat (IMF) content is closely related to meat quality and performance, such as tenderness and flavor. Abdominal fat (AF) in chickens is one of the main waste products at slaughter. Excessive AF reduces feed efficiency and carcass quality. RESULTS: To analyze the differential deposition of IMF and AF in chickens, gene expression profiles in the breast muscle (BM) and AF tissues of 18 animals were analyzed by differential expression analysis and weighted co-expression network analysis. The results showed that IMF deposition in BM was associated with pyruvate and citric acid metabolism through GAPDH, LDHA, GPX1, GBE1, and other genes. In contrast, AF deposition was related to acetyl CoA and glycerol metabolism through FABP1, ELOVL6, SCD, ADIPOQ, and other genes. Carbohydrate metabolism plays an essential role in IMF deposition, and fatty acid and glycerol metabolism regulate AF deposition. CONCLUSION: This study elucidated the molecular mechanism governing IMF and AF deposition through crucial genes and signaling pathways and provided a theoretical basis for producing high-quality broilers.


Assuntos
Galinhas , Glicerol , Gordura Abdominal/metabolismo , Tecido Adiposo/metabolismo , Animais , Galinhas/genética , Galinhas/metabolismo , Glicerol/metabolismo , Metabolismo dos Lipídeos/genética , Músculo Esquelético/metabolismo
10.
Sci Data ; 9(1): 156, 2022 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-35383184

RESUMO

This paper presents the curation of a monitored dataset from an office building constructed in 2015 in Berkeley, California. The dataset includes whole-building and end-use energy consumption, HVAC system operating conditions, indoor and outdoor environmental parameters, as well as occupant counts. The data were collected during a period of three years from more than 300 sensors and meters on two office floors (each 2,325 m2) of the building. A three-step data curation strategy is applied to transform the raw data into research-grade data: (1) cleaning the raw data to detect and adjust the outlier values and fill the data gaps; (2) creating the metadata model of the building systems and data points using the Brick schema; and (3) representing the metadata of the dataset using a semantic JSON schema. This dataset can be used in various applications-building energy benchmarking, load shape analysis, energy prediction, occupancy prediction and analytics, and HVAC controls-to improve the understanding and efficiency of building operations for reducing energy use, energy costs, and carbon emissions.

11.
Artigo em Inglês | MEDLINE | ID: mdl-35270452

RESUMO

In educational contexts, mentorship roles often complicate the mentor-student relationship because mentors act not only as the closest academic ally of graduate students but also their program supervisors who can affect their timely graduation. This study examines how graduate students react to their mentors' names when subliminally presented. A total of 63 graduate students (31 male; Mean Age = 23.450) were asked to perform an irrelevant color judgment task of valenced words (positive vs. negative relationship words) after a subliminal presentation of three different types of names (i.e., mentors, authorities, and friends). Results show that mentor and friend names elicit a greater P2 peak than authority names, whereas mentor names evoke a reduced N2 and P3 amplitude than friend and authority names. In addition, participants with a history of abusive supervision tend to have an overall decline in P2 amplitude. These event-related potential (ERP) findings suggest that mentors are perceived by students as familiar while attention-inducing figures.


Assuntos
Mentores , Estudantes , Adulto , Potenciais Evocados , Processos Grupais , Humanos , Masculino , Adulto Jovem
12.
Gland Surg ; 11(1): 100-114, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35242673

RESUMO

BACKGROUND: Whether tumor mutation burden (TMB) correlated with improved survival outcomes or promotion of immunotherapies remained controversy in various malignancies. We aimed to explore the prognostic value of TMB and the relationship between TMB and immune infiltration in human epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC). METHODS: We downloaded somatic mutation data and clinical information for 216 HER2+ BC patients from the The Cancer Genome Atlas (TCGA) and cBioPortal databases. Patients were divided into high- and low-TMB groups through TMB calculation. Cox regression analysis was used to establish an immune- and mutant-related risk model based on 5-hub genes. The relationship between 5-hub genes mutants and the level of immune infiltration, as well as the relationship between the risk model and the immune microenvironment were analyzed by "TIMER" database. RESULTS: TMB was negatively correlated with overall survival (OS) and disease-free survival (DFS), and high TMB may inhibit immune infiltration in HER2+ BC. Furthermore, risk score classified effectively patients into low- and high-risk groups in training and validation cohorts. The infiltration of CD4+ T cells and NK cells and the levels of immune checkpoint pathway genes were lower in the high-risk group, which indicated a poor prognosis. CONCLUSIONS: Higher TMB correlated with poor survival outcomes and might inhibit the immune infiltrates in HER2+ BC. The 5-hub TMB-related signature conferred lower immune cells infiltration which deserved further validation.

13.
Med Image Anal ; 78: 102413, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35305447

RESUMO

Functional magnetic resonance imaging (fMRI) as a promising tool to investigate psychotic disorders can be decomposed into useful imaging features such as time courses (TCs) of independent components (ICs) and functional network connectivity (FNC) calculated by TC cross-correlation. TCs reflect the temporal dynamics of brain activity and the FNC characterizes temporal coherence across intrinsic brain networks. Both features have been used as input to deep learning approaches with decent results. However, few studies have tried to leverage their complementary information to learn optimal representations at multiple facets. Motivated by this, we proposed a Hybrid Deep Learning Framework integrating brain Connectivity and Activity (HDLFCA) together by combining convolutional recurrent neural network (C-RNN) and deep neural network (DNN), aiming to improve classification accuracy and interpretability simultaneously. Specifically, C-RNNAM was proposed to extract temporal dynamic dependencies with an attention module (AM) to automatically learn discriminative knowledge from TC nodes, while DNN was applied to identify the most group-discriminative FNC patterns with layer-wise relevance propagation (LRP). Then, both prediction outputs were concatenated to build a new feature matrix, generating the final decision by logistic regression. The effectiveness of HDLFCA was validated on both multi-site schizophrenia (SZ, n ∼ 1100) and public autism datasets (ABIDE, n ∼ 1522) by outperforming 12 alternative models at 2.8-8.9% accuracy, including 8 models using either static FNC or TCs and 4 models using dynamic FNC. Appreciable classification accuracy was achieved for HC vs. SZ (85.3%) and HC vs. Autism (72.4%) respectively. More importantly, the most group-discriminative brain regions can be easily attributed and visualized, providing meaningful biological interpretability and highlighting the great potential of the proposed HDLFCA model in the identification of valid neuroimaging biomarkers.


Assuntos
Encéfalo/fisiopatologia , Aprendizado Profundo , Imageamento por Ressonância Magnética , Redes Neurais de Computação , Esquizofrenia , Encéfalo/patologia , Humanos , Imageamento por Ressonância Magnética/métodos , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/patologia
14.
J Hazard Mater ; 429: 127471, 2022 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-35236018

RESUMO

CuO/WO3 hierarchical hollow microspheres, assembled from irregular two dimensional (2D) nanosheets, were prepared by ultrasonic-wet chemical etching and pyrolysis in this study. The sensing performance of Micro-Electro-Mechanical System (MEMS) xylene gas sensor based on CuO/WO3 hierarchical structure were evaluated. It was found that the CuO/WO3 MEMS sensors showed an enhanced gas sensing performance compared with pristine WO3 sensor. The CuO/WO3-3 (the mass ratio of CuO to WO3 is 3%) sensor exhibited faster response-recover speed and the highest response value to xylene. Moreover, the CuO/WO3-3 sensor possessed higher selectivity and long-term stability. The good sensing properties can be attributed to the unique three dimensional (3D) hierarchical structure and p-n heterojunction of CuO-WO3. Considering the above advantages, the CuO/WO3-3 sensor has a great potential for the rapid detection and monitoring of xylene.

15.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 53(2): 335-341, 2022 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-35332739

RESUMO

Cholesterol, an important lipid molecule of organisms, is involved in the formation of cell membrane structure, bile acid metabolism and steroid hormone synthesis, playing an important role in the regulation of cell structure and functions. In recent years, a large number of studies have shown that cholesterol metabolism is reprogrammed during tumor formation and development. In addition to directly affecting the biological behavior of tumor cells, cholesterol metabolic reprogramming also regulates the antitumor activity of immune cells in the tumor microenvironment. We reviewed herein the cholesterol metabolism reprogramming of and interactions among immune cells including myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs), dendritic cells (DCs), and T cells in the tumor microenvironment. However, the relationship between cholesterol metabolism and tumor immunity in tumor microenvironment is complex and diversified. The differences and similarities of cholesterol metabolism reprogramming in tumor microenvironment in regulating immune cell activity and the specific regulatory mechanism are still unresolved issues. Targeted intervention of the cholesterol metabolism pathway of immune cells is expected to become a new strategy of cholesterol metabolism in tumor immunotherapy.


Assuntos
Células Supressoras Mieloides , Neoplasias , Humanos , Imunoterapia , Metabolismo dos Lipídeos , Células Supressoras Mieloides/metabolismo , Células Supressoras Mieloides/patologia , Microambiente Tumoral
16.
Front Cell Neurosci ; 16: 839023, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35221926

RESUMO

Ischemic stroke is a common cause of death and disability worldwide, which leads to serious neurological and physical dysfunction and results in heavy economic and social burdens. For now, timely and effective dissolution of thrombus, and ultimately improvement in the recovery of neurological functions, is the treatment strategy focus. Recently, many studies have reported that transcranial ultrasound stimulation (TUS), as a non-invasive method, can dissolve thrombus, improve cerebral blood circulation, and exert a neuroprotective effect post-stroke. TUS can promote functional recovery and improve rehabilitation efficacy among patients with ischemic stroke. This mini-review summarizes the potential mechanism and limitation of TUS in stroke aims to provide a new strategy for the future treatment of patients with ischemic stroke.

17.
Brief Bioinform ; 23(2)2022 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-35224614

RESUMO

Accurate identification of drug-target interactions (DTIs) plays a crucial role in drug discovery. Compared with traditional experimental methods that are labor-intensive and time-consuming, computational methods are more and more popular in recent years. Conventional computational methods almost simply view heterogeneous networks which integrate diverse drug-related and target-related dataset instead of fully exploring drug and target similarities. In this paper, we propose a new method, named DTIHNC, for $\mathbf{D}$rug-$\mathbf{T}$arget $\mathbf{I}$nteraction identification, which integrates $\mathbf{H}$eterogeneous $\mathbf{N}$etworks and $\mathbf{C}$ross-modal similarities calculated by relations between drugs, proteins, diseases and side effects. Firstly, the low-dimensional features of drugs, proteins, diseases and side effects are obtained from original features by a denoising autoencoder. Then, we construct a heterogeneous network across drug, protein, disease and side-effect nodes. In heterogeneous network, we exploit the heterogeneous graph attention operations to update the embedding of a node based on information in its 1-hop neighbors, and for multi-hop neighbor information, we propose random walk with restart aware graph attention to integrate more information through a larger neighborhood region. Next, we calculate cross-modal drug and protein similarities from cross-scale relations between drugs, proteins, diseases and side effects. Finally, a multiple-layer convolutional neural network deeply integrates similarity information of drugs and proteins with the embedding features obtained from heterogeneous graph attention network. Experiments have demonstrated its effectiveness and better performance than state-of-the-art methods. Datasets and a stand-alone package are provided on Github with website https://github.com/ningq669/DTIHNC.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Redes Neurais de Computação , Descoberta de Drogas , Interações Medicamentosas , Humanos , Proteínas/metabolismo
18.
Cancer Discov ; 12(4): 1106-1127, 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35046097

RESUMO

Remodeling of the microenvironment by tumor cells can activate pathways that favor cancer growth. Molecular delineation and targeting of such malignant-cell nonautonomous pathways may help overcome resistance to targeted therapies. Herein we leverage genetic mouse models, patient-derived xenografts, and patient samples to show that acute myeloid leukemia (AML) exploits peripheral serotonin signaling to remodel the endosteal niche to its advantage. AML progression requires the presence of serotonin receptor 1B (HTR1B) in osteoblasts and is driven by AML-secreted kynurenine, which acts as an oncometabolite and HTR1B ligand. AML cells utilize kynurenine to induce a proinflammatory state in osteoblasts that, through the acute-phase protein serum amyloid A (SAA), acts in a positive feedback loop on leukemia cells by increasing expression of IDO1-the rate-limiting enzyme for kynurenine synthesis-thereby enabling AML progression. This leukemia-osteoblast cross-talk, conferred by the kynurenine-HTR1B-SAA-IDO1 axis, could be exploited as a niche-focused therapeutic approach against AML, opening new avenues for cancer treatment. SIGNIFICANCE: AML remains recalcitrant to treatments due to the emergence of resistant clones. We show a leukemia-cell nonautonomous progression mechanism that involves activation of a kynurenine-HTR1B-SAA-IDO1 axis between AML cells and osteoblasts. Targeting the niche by interrupting this axis can be pharmacologically harnessed to hamper AML progression and overcome therapy resistance. This article is highlighted in the In This Issue feature, p. 873.


Assuntos
Cinurenina , Leucemia Mieloide Aguda , Animais , Humanos , Cinurenina/metabolismo , Cinurenina/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Camundongos , Osteoblastos/metabolismo , Transdução de Sinais , Microambiente Tumoral
19.
Sci Rep ; 12(1): 687, 2022 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-35027588

RESUMO

The current diagnostic technologies for assessing the axillary lymph node metastasis (ALNM) status accurately in breast cancer (BC) remain unsatisfactory. Here, we developed a diagnostic model for evaluating the ALNM status using a combination of mRNAs and the T stage of the primary tumor as a novel biomarker. We collected relevant information on T1-2 BC from public databases. An ALNM prediction model was developed by logistic regression based on the screened signatures and then internally and externally validated. Calibration curves and the area under the curve (AUC) were employed as performance metrics. The prognostic value and tumor immune infiltration of the model were also determined. An optimal diagnostic model was created using a combination of 11 mRNAs and T stage of the primary tumor and showed high discrimination, with AUCs of 0.828 and 0.746 in the training sets. AUCs of 0.671 and 0.783 were achieved in the internal validation cohorts. The mean external AUC value was 0.686 and ranged between 0.644 and 0.742. Moreover, the new model has good specificity in T1 and hormone receptor-negative/human epidermal growth factor receptor 2- negative (HR-/HER2-) BC and good sensitivity in T2 BC. In addition, the risk of ALNM and 11 mRNAs were correlated with the infiltration of M2 macrophages, as well as the prognosis of BC. This novel prediction model is a useful tool to identify the risk of ALNM in T1-2 BC patients, particularly given that it can be used to adjust surgical options in the future.


Assuntos
Axila , Neoplasias da Mama/patologia , Metástase Linfática/diagnóstico , Modelos Teóricos , Área Sob a Curva , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Feminino , Previsões , Humanos , Modelos Logísticos , Metástase Linfática/genética , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , RNA Mensageiro , Receptor ErbB-2 , Risco
20.
Radiat Res ; 197(4): 350-364, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-34982167

RESUMO

Radiation-induced brain injury is a common complication of brain irradiation that eventually leads to irreversible cognitive impairment. Evidence has shown that the gut microbiome may play an important role in radiation-induced cognitive function. However, the effects of gut microbiota on radiation-induced brain injury (RIBI) remain poorly understood. Here we studied the link between intestinal microbes and radiation-induced brain injury to further investigate the effects of intestinal bacteria on neuroinflammation and cognitive function. We first verified the differences in gut microbes between male and female mice and administered antibiotics to C57BL/6 male mice to deplete the gut flora and then expose mice to radiation. We found that depletion of intestinal flora after irradiation may act as a protective modulator against radiation-induced brain injury. Moreover, we found that pretreatment with depleted gut microbes in RIBI mice suppressed brain pro-inflammatory factor production, and high-throughput sequencing analysis of mouse feces at 1-month postirradiation revealed microbial differences. Interestingly, a proportion of Verrucomicrobia Akkermansia showed partial recovery. Additionally, short-chain fatty acid treatments increased neuroinflammation in the radiation-induced brain injury model. Although a further increase in cognitive function was not observed, brain injury was aggravated in whole-brain irradiated mice to some extent. The protective effects of depleted intestinal flora and the utilization of the brain-gut axis open new avenues for development of innovative therapeutic strategies for radiation-induced brain injury.


Assuntos
Lesões Encefálicas , Disfunção Cognitiva , Microbioma Gastrointestinal , Lesões por Radiação , Animais , Disfunção Cognitiva/etiologia , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Lesões por Radiação/complicações
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