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1.
Medicine (Baltimore) ; 103(16): e37798, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38640295

RESUMO

Although several studies have reported a link between chronic atrophic gastritis (CAG) and atherosclerosis, the underlying mechanisms have not been elucidated. The present study aimed to investigate the molecular mechanisms common to both diseases from a bioinformatics perspective. Gene expression profiles were obtained from the Gene Expression Omnibus database. Data on atherosclerosis and CAG were downloaded from the GSE28829 and GSE60662 datasets, respectively. We identified the differentially expressed genes co-expressed in CAG and atherosclerosis before subsequent analyses. We constructed and identified the hub genes and performed functional annotation. Finally, the transcription factor (TF)-target genes regulatory network was constructed. In addition, we validated core genes and certain TFs. We identified 116 common differentially expressed genes after analyzing the 2 datasets (GSE60662 and GSE28829). Functional analysis highlighted the significant contribution of immune responses and the positive regulation of tumor necrosis factor production and T cells. In addition, phagosomes, leukocyte transendothelial migration, and cell adhesion molecules strongly correlated with both diseases. Furthermore, 16 essential hub genes were selected with cytoHubba, including PTPRC, TYROBP, ITGB2, LCP2, ITGAM, FCGR3A, CSF1R, IRF8, C1QB, TLR2, IL10RA, ITGAX, CYBB, LAPTM5, CD53, CCL4, and LY86. Finally, we searched for key gene-related TFs, especially SPI1. Our findings reveal a shared pathogenesis between CAG and atherosclerosis. Such joint pathways and hub genes provide new insights for further studies.


Assuntos
Aterosclerose , Gastrite Atrófica , Humanos , Gastrite Atrófica/genética , Aterosclerose/genética , Movimento Celular , Biologia Computacional , Análise de Dados , Perfilação da Expressão Gênica
2.
Ann Biomed Eng ; 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38658477

RESUMO

Understanding of human neck stiffness and range of motion (ROM) with minimal neck muscle activation ("passive") is important for clinical and bioengineering applications. The aim of this study was to develop, implement, and evaluate the reliability of methods for assessing passive-lying stiffness and ROM, in six head-neck rotation directions. Six participants completed two assessment sessions. To perform passive-lying tests, the participant's head and torso were strapped to a bending (flexion, extension, lateral bending) or a rotation (axial rotation) apparatus, and clinical bed, respectively. The head and neck were manually rotated by the researcher to the participant's maximum ROM, to assess passive-lying stiffness. Participant-initiated ("active") head ROM was also assessed in the apparatus, and seated. Various measures of apparatus functionality were assessed. ROM was similar for all assessment configurations in each motion direction except flexion. In each direction, passive stiffness generally increased throughout neck rotation. Within-session reliability for stiffness (ICC > 0.656) and ROM (ICC > 0.872) was acceptable, but between-session reliability was low for some motion directions, probably due to intrinsic participant factors, participant-apparatus interaction, and the relatively low participant number. Moment-angle corridors from both assessment sessions were similar, suggesting that with greater sample size, these methods may be suitable for estimating population-level corridors.

3.
Psychol Res Behav Manag ; 17: 1339-1353, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38524285

RESUMO

Purpose: In recent years, due to the increasingly prominent role of voice behavior in leader decision-making and organizational performance, such behavior has become a central topic for scholars. A majority of studies explore the "uphold" effects of multiple leader behavior toward the voice behavior; nonetheless, our study revealed the "undo" effect --- leader hypocrisy on voice behavior. Drawing on social cognitive theory, we investigated the relationship between leader hypocrisy and voice behavior, examined the mediating effects of cognition-based trust and affect-based trust, and the moderating effect of moral identity. Patients and Methods: We conducted a three-wave survey in a large Chinese corporation to test the hypothesized model. We collected 562 employees to participate in this survey. Results: The results show that leader hypocrisy negatively impacts employees' cognition-based and affect-based trust, and both types of trust mediate the relationship between leader hypocrisy and voice behavior, respectively. In the meantime, moral identity manifested the negative effect of leader hypocrisy on cognition-based and affect-based trust. Conclusion: Our research not only enriches the related research on leader hypocrisy and voice behavior but also uncovers the underlying mechanism through which leader hypocrisy affects voice behavior and the boundary conditions of this effect. Meanwhile, our research provides a theoretical reference for increasing employees' voice behavior and promoting the healthy development of enterprises.

4.
Int J Mol Sci ; 25(5)2024 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-38473906

RESUMO

Many metastatic cancers with poor prognoses correlate to downregulated CD82, but exceptions exist. Understanding the context of this correlation is essential to CD82 as a prognostic biomarker and therapeutic target. Oral squamous cell carcinoma (OSCC) constitutes over 90% of oral cancer. We aimed to uncover the function and mechanism of CD82 in OSCC. We investigated CD82 in human OSCC cell lines, tissues, and healthy controls using the CRISPR-Cas9 gene knockout, transcriptomics, proteomics, etc. CD82 expression is elevated in CAL 27 cells. Knockout CD82 altered over 300 genes and proteins and inhibited cell migration. Furthermore, CD82 expression correlates with S100 proteins in CAL 27, CD82KO, SCC-25, and S-G cells and some OSCC tissues. The 37-50 kDa CD82 protein in CAL 27 cells is upregulated, glycosylated, and truncated. CD82 correlates with S100 proteins and may regulate their expression and cell migration. The truncated CD82 explains the invasive metastasis and poor outcome of the CAL 27 donor. OSCC with upregulated truncated CD82 and S100A7 may represent a distinct subtype with a poor prognosis. Differing alternatives from wild-type CD82 may elucidate the contradictory functions and pave the way for CD82 as a prognostic biomarker and therapeutic target.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Bucais , Humanos , Neoplasias Bucais/patologia , Carcinoma de Células Escamosas/metabolismo , Proteína Kangai-1/metabolismo , Tetraspaninas/metabolismo , Proteínas S100 , Biomarcadores , Proteína A7 Ligante de Cálcio S100
5.
Phys Chem Chem Phys ; 26(12): 9295-9308, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38469695

RESUMO

Understanding selectivity mechanisms of inhibitors towards highly homologous proteins is of paramount importance in the design of selective candidates. Human aldo-keto reductases (AKRs) pertain to a superfamily of monomeric oxidoreductases, which serve as NADPH-dependent cytosolic enzymes to catalyze the reduction of carbonyl groups to primary and secondary alcohols using electrons from NADPH. Among AKRs, AKR1B1 is emerging as a promising target for cancer treatment and diabetes, despite its high structural similarity with AKR1B10, which leads to severe adverse events. Therefore, it is crucial to understand the selectivity mechanisms of AKR1B1 and AKR1B10 to discover safe anticancer candidates with optimal therapeutic efficacy. In this study, multiple computational strategies, including sequence alignment, structural comparison, Protein Contacts Atlas analysis, molecular docking, molecular dynamics simulation, MM-GBSA calculation, alanine scanning mutagenesis and pharmacophore modeling analysis were employed to comprehensively understand the selectivity mechanisms of AKR1B1/10 inhibition based on selective inhibitor lidorestat and HAHE. This study would provide substantial evidence in the design of potent and highly selective AKR1B1/10 inhibitors in future.


Assuntos
Inibidores Enzimáticos , Simulação de Dinâmica Molecular , Humanos , Simulação de Acoplamento Molecular , NADP/metabolismo , Aldo-Ceto Redutases/metabolismo , Inibidores Enzimáticos/farmacologia , Aldeído Redutase/metabolismo
6.
Heliyon ; 10(5): e27107, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38434265

RESUMO

TTMV::RARA is a recently reported fusion gene associated with acute promyelocytic leukemia (APL), caused by the integration of torque teno mini virus (TTMV) genomic fragments into the second intron of the RARA gene. Currently, there have been only six documented cases, with clinical presentations showing significant variability. Although initial responses to all-trans retinoic acid (ATRA) treatment may be observed in patients with TTMV::RARA-APL, the overall prognosis remains unfavorable among infrequent reported cases. This article presents a pediatric case that manifested as PML::RARA-negative APL with central nervous system involvement at onset. The patient experienced both intramedullary and extramedullary relapse one year after undergoing allogeneic hematopoietic stem cell transplantation. Upon identification as TTMV::RARA-APL and subsequent administration of two rounds of ATRA-based treatment, the patient rapidly developed multiple RARA ligand-binding domain mutations and demonstrated extensive resistance to ATRA and various other therapeutic interventions. Additionally, the patient experienced ARID1A mutant clone expansion and progressed MYC-targeted gene activation. This case represents the first documentation of extramedullary involvement at both the initial diagnosis and relapse stages, emphasizing the intricate clinical features and challenges associated with the rapid accumulation of multiple ATRA-resistant mutations in TTMV::RARA-APL, characterizing it as a distinct and complex sub-entity of atypical APL.

7.
Front Oncol ; 14: 1289265, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38476364

RESUMO

Background: The diagnosis of gastric atrophy is highly subjective, and we aimed to establish a model of gastric atrophy based on pathological features to improve diagnostic consistency. Methods: We retrospectively collected the HE-stained pathological slides of gastric biopsies and used CellProfiler software for image segmentation and feature extraction of ten representative images for each sample. Subsequently, we employed the Least absolute shrinkage and selection operator (LASSO) to select features and different machine learning (ML) algorithms to construct the diagnostic models for gastric atrophy. Results: We selected 289 gastric biopsy specimens for training, testing, and external validation. We extracted 464 pathological features and screened ten features by LASSO to establish the diagnostic model for moderate-to-severe atrophy. The range of area under the curve (AUC) for various machine learning algorithms was 0.835-1.000 in the training set, 0.786-0.949 in the testing set, and 0.689-0.818 in the external validation set. LR model had the highest AUC value, with 0.900 (95% CI: 0.852-0.947) in the training set, 0.901 (95% CI: 0.807-0.996) in the testing set, and 0.818 (95% CI: 0.714-0.923) in the external validation set. The atrophy pathological score based on the LR model was associated with endoscopic atrophy grading (Z=-2.478, P=0.013) and gastric cancer (GC) (OR=5.70, 95% CI: 2.63-12.33, P<0.001). Conclusion: The ML model based on pathological features could improve the diagnostic consistency of gastric atrophy, which is also associated with endoscopic atrophy grading and GC.

8.
Am J Hematol ; 99(5): 824-835, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38321864

RESUMO

Two recent guidelines, the 5th edition of the World Health Organization Classification of Haematolymphoid Tumours (WHO-HAEM5) and the International Consensus Classification (ICC), were published to refine the diagnostic criteria of acute myeloid leukemia (AML). They both consider genomic features more extensively and expand molecularly defined AML subtypes. In this study, we compared the classifications of 1135 AML cases under both criteria. According to WHO-HAEM5 and ICC, the integration of whole transcriptome sequencing, targeted gene mutation screening, and conventional cytogenetic analysis identified defining genetic abnormalities in 89% and 90% of AML patients, respectively. The classifications displayed discrepancies in 16% of AML cases after being classified using the two guidelines, respectively. Both new criteria significantly reduce the number of cases defined by morphology and differentiation. However, their clinical implementation heavily relies on comprehensive and sophisticated genomic analysis, including genome and transcriptome levels, alongside the assessment of pathogenetic somatic and germline variations. Discrepancies between WHO-HAEM5 and ICC, such as the assignment of RUNX1 mutations, the rationality of designating AML with mutated TP53 as a unique entity, and the scope of rare genetic fusions, along with the priority of concurrent AML-defining genetic abnormalities, are still pending questions requiring further research for more elucidated insights.


Assuntos
Leucemia Mieloide Aguda , Humanos , Consenso , Mutação , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Genômica , Organização Mundial da Saúde
9.
PLoS One ; 19(2): e0299647, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38422049

RESUMO

A suction bucket foundation is a new type offering high construction efficiency, precise positioning, cost-effectiveness, and environmental friendliness. It has been extensively employed in marine resource development, particularly in offshore wind power and oil and gas extraction. It usually involves multiple suction bucket conduit rack platforms during offshore construction projects. Accurately predicting the sinking penetration resistance and determining the suction value is crucial during the construction of the suction bucket foundation, as it ensures the safe sinking of the platform foundation to the designated depth. This paper examines the feasibility of the suction bucket foundation's sinking, sinking penetration resistance, suction value, and self-weight penetration depth, using the offshore wind farm guiding frame platform foundation project in Yangjiang, Guangdong Province, as a basis of analysis. The measured data is analyzed using the API specification static equilibrium analysis method, ABAQUS finite element analysis, and data mining techniques. The suction drum base platform's sinking process was monitored for negative pressure and penetration resistance. These observed values were compared to theoretical and finite element calculations. Results demonstrated that the API specification's theoretical calculations and finite element analyses effectively predict sinking penetration resistance, the suction force value, and the penetration depth for self-gravitational penetration. On-site engineering data fit these theoretical calculations, and finite element analyses well. The findings from this study have enriched the engineering application database of the suction drum foundation, providing a valuable reference for the design and construction of similar projects and establishing the groundwork for further promotion and application.


Assuntos
Sucção , Análise de Elementos Finitos
10.
J Dent Sci ; 19(1): 39-45, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38303823

RESUMO

Background/purpose: The guided protocols always yield a higher accuracy than freehand surgery. However, the accuracy of digital guides for crown lengthening surgery (CLS) is unknown. The purpose of this study was to evaluate the trueness of 3 types of digital guides for CLS. Materials and methods: Twenty individually designed maxillary models were divided into 4 groups according to surgical guides: type I (T1), type II (T2), type III (T3), and free-hand. T1 comprised a planed gingival margin at the tissue level. T2 included both the planed gingival margin and alveolar crest at the tissue level. T3 consisted of a planed gingival margin at the tissue level and an alveolar crest at the bone level. CLS was performed under the indication of the guides. Trueness of the guides was evaluated through the deviation of the gingival zenith and alveolar crest height. Results: The control group had higher vertical and horizontal distance deviations of gingival zenith compared to the 3 digital guide groups (P < 0.001). There were no significant differences among the 3 test groups in terms of gingival zenith deviations (P > 0.05). With regard to height deviation of alveolar crest, the control and T1 groups were higher than T2 group (P < 0.001), while T3 group had the lowest deviations among the 4 groups (P < 0.001). Conclusion: The digital guides assisted CLS procedures are more accurate than free-hand method. The trueness of type III guide was better than type I and type II.

11.
Adv Sci (Weinh) ; 11(12): e2306305, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38225741

RESUMO

The scar repair inevitably causes damage of skin function and loss of skin appendages such as hair follicles (HF). It is of great challenge in wound repair that how to intervene in scar formation while simultaneously remodeling HF niche and inducing in situ HF regeneration. Here, chemical reprogramming techniques are used to identify a clinically chemical cocktail (Tideglusib and Tamibarotene) that can drive fibroblasts toward dermal papilla cell (DPC) fate. Considering the advantage of biomaterials in tissue repair and their regulation in cell behavior that may contributes to cellular reprogramming, the artificial HF seeding (AHFS) hydrogel microspheres, inspired by the natural processes of "seeding and harvest", are constructed via using a combination of liposome nanoparticle drug delivery system, photoresponsive hydrogel shell, positively charged polyamide modification, microfluidic and photocrosslinking techniques. The identified chemical cocktail is as the core nucleus of AHFS. In vitro and in vivo studies show that AHFS can regulate fibroblast fate, induce fibroblast-to-DPC reprogramming by activating the PI3K/AKT pathway, finally promoting wound healing and in situ HF regeneration while inhibiting scar formation in a two-pronged translational approach. In conclusion, AHFS provides a new and effective strategy for functional repair of skin wounds.


Assuntos
Folículo Piloso , Cicatrização , Humanos , Cicatrização/fisiologia , Cicatriz/patologia , Regeneração/fisiologia , Hidrogéis/farmacologia , Microesferas , Fosfatidilinositol 3-Quinases/farmacologia
12.
Respir Physiol Neurobiol ; 322: 104219, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38242336

RESUMO

Acute Lung Injury (ALI) manifests as an acute exacerbation of pulmonary inflammation with high mortality. The potential application of Danshensu methyl ester (DME, synthesized in our lab) in ameliorating ALI has not been elucidated. Our results demonstrated that DME led to a remarkable reduction in lung injury. DME promoted a marked increase in antioxidant enzymes, like superoxide dismutase (SOD), and glutathione (GSH), accompanied by a substantial decrease in reactive oxygen species (ROS), myeloperoxidase (MPO), and malondialdehyde (MDA). Moreover, DME decreased the production of IL-1ß, TNF-α and IL-6, in vitro and in vivo. TLR4 and MyD88 expression is reduced in the DME-treated cells or tissues, which further leading to a decrease of p-p65 and p-IκBα. Meanwhile, DME effectively facilitated an elevation in cytoplasmic p65 expression. In summary, DME could ameliorate ALI by its antioxidant functionality and anti-inflammation effects through TLR4/NF-κB, which implied that DME may be a viable medicine for lung injury.


Assuntos
Lesão Pulmonar Aguda , Lactatos , NF-kappa B , Humanos , NF-kappa B/metabolismo , Transdução de Sinais , Lipopolissacarídeos/toxicidade , Receptor 4 Toll-Like , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/metabolismo , Glutationa
13.
Int J Biol Macromol ; 259(Pt 2): 129283, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38199538

RESUMO

Diabetic wounds, resulting from skin atrophy due to localized ischemia and hypoxia in diabetic patients, lead to chronic pathological inflammation and delayed healing. Using electrospinning technology, we developed magnesium ion-chelated nanofiber membranes to explore their efficacy in antibacterial, anti-inflammatory, and angiogenic applications for wound healing. These membranes are flexible and elastic, resembling native skin tissue, and possess good hydrophilicity for comfortable wound bed contact. The mechanical properties of nanofiber membranes are enhanced by the chelation of magnesium ions (Mg2+), which also facilitates a long-term slow release of Mg2+. The cytocompatibility of the nanofibrous membranes is influenced by their Mg2+ content: lower levels encourage the proliferation of fibroblasts, endothelial cells, and macrophages, while higher levels are inhibitory. In a diabetic rat model, magnesium ion-chelated nanofibrous membranes effectively reduced early wound inflammation and notably accelerated wound healing. This study highlights the potential of magnesium ion-chelated nanofiber membranes in treating diabetic wounds.


Assuntos
Diabetes Mellitus , Nanofibras , Humanos , Ratos , Animais , Magnésio/farmacologia , Células Endoteliais/patologia , Cicatrização , Diabetes Mellitus/patologia , Inflamação
14.
J Org Chem ; 89(1): 304-312, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38126126

RESUMO

An effective Ag(I)-mediated annulation of 2-(2-enynyl)pyridines and propargyl amines was developed, unexpectedly affording a broad range of functionalized 1-(2H-pyrrol-3-yl)indolizines in moderate to excellent yields. The developed method is characterized by operational simplicity, ready availability of starting materials, high regioselectivity, and broad substrate scope under mild reaction conditions. The Ag(I)-promoted cyclization of 2-(2-enynyl)pyridines and propargyl amines possibly results in the formation of the spiroindolizine, the ring-opening rearrangement of which may give the 1-(2H-pyrrol-3-yl)indolizine. Furthermore, a gram-scale reaction and synthetic transformations are also studied.

15.
Technol Health Care ; 2023 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-38073341

RESUMO

BACKGROUND: Oral squamous cell carcinoma (OSCC) is an infiltrative malignancy characterized by a significantly elevated recurrence rate. Dickkopf-related protein 1 (DKK1), which plays an oncogene role in many cancers, acts as an inhibitor of the Wingless protein (Wnt) signaling pathway. Currently, there is a lack of consensus regarding the role of DKK1 in OSCC or its clinical significance. OBJECTIVE: To examine the role and effect of DKK1 in OSCC. METHODS: The identification of differentially expressed genes (DEGs) in OSCC was conducted by utilizing databases such as The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). A comprehensive analysis of gene expression profile interactions (GEPIA) and Kaplan-Meier curve were conducted to investigate the associations among DEGs, patient survival and prognosis in individuals with OSCC. The biological function of DKK1 in OSCC was investigated by using molecular biology approaches. RESULTS: The expression of DKK1 was found to be upregulated in OSCC tissues at various stages. High levels of DKK1 expression exhibited a positive correlation with the overall survival (OS) and progression-free survival (PFS) rates among OSCC patients. DKK1 knockdown suppressed the proliferation and induced apoptotic response in OSCC cells. Moreover, DKK1 exerted a positive regulatory effect on HMGA2 expression, thereby modulating cell growth and apoptosis in OSCC. The expression of DKK1 was found to be positively correlated with the infiltration of immune cells in patients with OSCC. Additionally, higher levels of CD4+ T cells were associated with improved 5-year survival rates. CONCLUSION: DKK1 is a prognostic biomarker for patients with OSCC.

16.
Comput Struct Biotechnol J ; 21: 5751-5764, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38074471

RESUMO

The incidence of lung cancer (LC) in Idiopathic Pulmonary Fibrosis (IPF) patients is more than twice that in non-IPF. This study aims to investigate IPF-to-LC pathogenesis and to develop a predictor for detecting IPF predisposing patients to LC. We conducted unsupervised clustering to detect high-risk subtypes from IPF to LC. Subsequently, we performed single-cell RNA-seq analysis to characterize high-risk IPF by examining the immune microenvironment. We identified 42 common immune function-related pathogenic genes between IPF and LC. We developed an LC risk classifier for IPF patients, comprising five genes: SPP1, MMP9, MMP12, FABP4, and IL1B. The five-gene classifier can successfully distinguish the high-risk population from IPF patients. High-risk IPF patients exhibited an immunosuppressive microenvironment with higher oncogene expression than low-risk patients. Single-cell analysis revealed that SPP1+ macrophages at the terminal of macrophages' developmental trajectory may promote the progression from IPF to LC. The strong crosstalk between SPP1+ macrophages and inflammation-related cancer-associated fibroblasts promoted the tumorigenic process in IPF. In vitro, assays showed that co-culturing macrophages overexpressing SPP1 with MRC-5 cells induced the transition of fibroblasts into cancer-associated fibroblasts. SPP1 produced by macrophages promoted epithelial-mesenchymal transition in alveolar epithelial cells via stimulating the upregulation of N-cadherin and Vimentin in MLE-12 cells. This study provided a novel method to identify the LC risk population from IPF, revealing the cellular interactions involved in the transition from IPF to LC. Our findings highlighted SPP1 as a critical driver in IPF progression, offering a potential target for therapy in fibrosis.

17.
Elife ; 122023 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-38127423

RESUMO

Germline CTLA-4 deficiency causes severe autoimmune diseases characterized by dysregulation of Foxp3+ Tregs, hyper-activation of effector memory T cells, and variable forms autoimmune cytopenia including gradual loss of B cells. Cancer patients with severe immune-related adverse events (irAE) after receiving anti-CTLA-4/PD-1 combination immunotherapy also have markedly reduced peripheral B cells. The immunological basis for B cell loss remains unexplained. Here, we probe the decline of B cells in human CTLA-4 knock-in mice by using anti-human CTLA-4 antibody Ipilimumab conjugated to a drug payload emtansine (Anti-CTLA-4 ADC). The anti-CTLA-4 ADC-treated mice have T cell hyper-proliferation and their differentiation into effector cells which results in B cell depletion. B cell depletion is mediated by both CD4 and CD8 T cells and at least partially rescued by anti-TNF-alpha antibody. These data revealed an unexpected antagonism between T and B cells and the importance of regulatory T cells in preserving B cells.


Assuntos
Abatacepte , Linfócitos B , Linfócitos T Reguladores , Linfócitos B/efeitos dos fármacos , Linfócitos B/imunologia , Abatacepte/farmacologia , Animais , Camundongos , Antígeno CTLA-4/genética , Antígeno CTLA-4/imunologia , Depleção Linfocítica , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/imunologia , Apoptose/efeitos dos fármacos , Imunoglobulinas/sangue , Imunoglobulinas/imunologia , Células CHO , Cricetulus , Camundongos Endogâmicos C57BL , Masculino , Feminino
18.
Cell Cycle ; 22(20): 2229-2244, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37974462

RESUMO

Identifying robust breast cancer subtypes will help to reveal the cancer heterogeneity. However, previous breast cancer subtypes were based on population-level quantitative gene expression, which is affected by batch effects and cannot be applied to individuals. We detected differential gene expression, genomic, and epigenomic alterations to identify driver differential expression at the individual level. The individual driver differential expression reflected the breast cancer patients' heterogeneity and revealed four subtypes. Mesenchymal subtype as the most aggressive subtype harbored deletion and downregulated expression of genes in chromosome 11q23 region. Specifically, silencing of the SDHD gene in 11q23 promoted the invasion and migration of breast cancer cells in vitro by the epithelial-mesenchymal transition. The immunologically hot subtype displayed an immune-hot microenvironment, including high T-cell infiltration and upregulated PD-1 and CTLA4. Luminal and genomic-unstable subtypes showed opposite macrophage polarization, which may be regulated by the ligand-receptor pairs of CD99. The integration of multi-omics data at the individual level provides a powerful framework for elucidating the heterogeneity of breast cancer.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Perfilação da Expressão Gênica , Multiômica , Genômica , Epigenômica , Microambiente Tumoral/genética
19.
Food Res Int ; 174(Pt 2): 113647, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37981361

RESUMO

This study aimed to improve the complexing degree, digestibility and controlled release properties of the potato starch (PS)-linoleic acid (LA) complexes by encapsulating PS-LA complexes to sodium alginate (AG) beads. The results revealed that AG had a positive effect on the complexing index, R1047/1022 values, relative crystallinity, enthalpy and morphological structure of PS-LA-AG films, especially for PS-LA-AG film with the PS-LA: AG of 5:1. The in vitro digestion and hydrolysis kinetic analysis indicated that AG addition reduced the digestibility of PS-LA-AG films to a higher slowly digestible starch content and resistant starch content and a lower equilibrium hydrolysis percentage and kinetic constant. Furthermore, in vivo release study of PS-LA-AG films indicated a restrained release in simulated gastrointestinal conditions. Consequently, the results indicated that AG addition significantly improved the inclusion efficiency for the complex formation between PS and LA, which was beneficial for the design of resistant films to entrap and control release of unsaturated fatty.


Assuntos
Ácido Linoleico , Amido , Cinética , Alginatos , Suplementos Nutricionais
20.
Nanomaterials (Basel) ; 13(21)2023 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-37947676

RESUMO

The fast rise of organic pollution has posed severe health risks to human beings and toxic issues to ecosystems. Proper disposal toward these organic contaminants is significant to maintain a green and sustainable development. Among various techniques for environmental remediation, advanced oxidation processes (AOPs) can non-selectively oxidize and mineralize organic contaminants into CO2, H2O, and inorganic salts using free radicals that are generated from the activation of oxidants, such as persulfate, H2O2, O2, peracetic acid, periodate, percarbonate, etc., while the activation of oxidants using catalysts via Fenton-type reactions is crucial for the production of reactive oxygen species (ROS), i.e., •OH, •SO4-, •O2-, •O3CCH3, •O2CCH3, •IO3, •CO3-, and 1O2. Nanoscale zero-valent iron (nZVI), with a core of Fe0 that performs a sustained activation effect in AOPs by gradually releasing ferrous ions, has been demonstrated as a cost-effective, high reactivity, easy recovery, easy recycling, and environmentally friendly heterogeneous catalyst of AOPs. The combination of nZVI and AOPs, providing an appropriate way for the complete degradation of organic pollutants via indiscriminate oxidation of ROS, is emerging as an important technique for environmental remediation and has received considerable attention in the last decade. The following review comprises a short survey of the most recent reports in the applications of nZVI participating AOPs, their mechanisms, and future prospects. It contains six sections, an introduction into the theme, applications of persulfate, hydrogen peroxide, oxygen, and other oxidants-based AOPs catalyzed with nZVI, and conclusions about the reported research with perspectives for future developments. Elucidation of the applications and mechanisms of nZVI-based AOPs with various oxidants may not only pave the way to more affordable AOP protocols, but may also promote exploration and fabrication of more effective and sustainable nZVI materials applicable in practical applications.

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