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1.
Nat Immunol ; 19(3): 279-290, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-29434353

RESUMEN

Deletion of master regulators of the B cell lineage reprograms B cells into T cells. Here we found that the transcription factor Hoxb5, which is expressed in uncommitted hematopoietic progenitor cells but is not present in cells committed to the B cell or T cell lineage, was able to reprogram pro-pre-B cells into functional early T cell lineage progenitors. This reprogramming started in the bone marrow and was completed in the thymus and gave rise to T lymphocytes with transcriptomes, hierarchical differentiation, tissue distribution and immunological functions that closely resembled those of their natural counterparts. Hoxb5 repressed B cell 'master genes', activated regulators of T cells and regulated crucial chromatin modifiers in pro-pre-B cells and ultimately drove the B cell fate-to-T cell fate conversion. Our results provide a de novo paradigm for the generation of functional T cells through reprogramming in vivo.


Asunto(s)
Linfocitos B/citología , Linaje de la Célula/inmunología , Reprogramación Celular/inmunología , Proteínas de Homeodominio/inmunología , Linfocitos T/citología , Animales , Diferenciación Celular , Linaje de la Célula/genética , Reprogramación Celular/genética , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Endogámicos NOD , Ratones SCID , Células Precursoras de Linfocitos B/citología
2.
Nat Immunol ; 19(9): 1036, 2018 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-29915300

RESUMEN

In the version of this article initially published, some identification of the supplementary information was incorrect. The items originally called Supplementary Tables 1, 2, 3, 4 and 5 should be Source Data Figures 1, 2, 4, 5 and 7, respectively; those originally called Supplementary Tables 6, 7 and 8 should be Supplementary Tables 1, 2 and 3, respectively; and those originally called Source Data Figures 1, 2, 4, 5 and 7 should be Supplementary Tables 4, 5, 6, 7 and 8, respectively. The errors have been corrected in the HTML version of the article.

3.
Anal Chem ; 95(6): 3532-3543, 2023 02 14.
Artículo en Inglés | MEDLINE | ID: mdl-36744576

RESUMEN

Phospholipid-based materials exhibit great application potential in the fields of chemistry, biology, and pharmaceutical sciences. In this study, an inside-out oriented choline phosphate molecule, 2-{2-(methacryloyloxy)ethyldimethylammonium}ethyl n-butyl phosphate (MBP), was proposed and verified as a novel ligand of C-reactive protein (CRP) to enrich the functionality of these materials. Compared with phosphorylcholine (PC)-CRP interactions, the binding between MBP and CRP was not affected by the reverse position of phosphate and choline groups and even found more abundant binding sites. Thus, high-density MBP-grafted biomimetic magnetic nanomaterials (MBP-MNPs) were fabricated by reversible addition-fragmentation chain transfer polymerization based on thiol-ene click chemistry. The novel materials exhibited multifunctional applications for CRP including purification and ultrasensitive detection. On the one hand, higher specificity, recovery (90%), purity (95%), and static binding capacity (198.14 mg/g) for CRP were achieved on the novel materials in comparison with traditional PC-based materials, and the enriched CRP from patient serum can maintain its structural integrity and bioactivity. On the other hand, the CRP detection method combining G-quadruplex and thioflavin T developed with MBP-MNPs showed a lower detection limit (10 pM) and wider linear range (0.1-50 nM) than most PC-functionalized analytical platforms. Therefore, the inside-out oriented choline phosphate can not only precisely recognize CRP but also be combined with biomimetic nanomaterials to provide high application potential.


Asunto(s)
Proteína C-Reactiva , Fosforilcolina , Humanos , Fosforilcolina/química , Proteína C-Reactiva/análisis , Biomimética , Fenómenos Magnéticos , Fosfatos
4.
Analyst ; 149(1): 212-220, 2023 Dec 18.
Artículo en Inglés | MEDLINE | ID: mdl-38018757

RESUMEN

The accurate and rapid detection of specific antibodies in blood is very important for efficient diagnosis and precise treatment. Conventional methods often suffer from time-consuming operations and/or a narrow detection range. In this work, for the rapid determination of bevacizumab in plasma, a series of chimeric hairpin DNA aptamer-based probes were designed by the modification, labeling and theoretical computation of an original aptamer. Then, the dissociation constant of the modified hairpin DNA to bevacizumab was measured and screened using microscale thermophoresis. The best chimeric hairpin DNA aptamer-based probe was then selected, and a one-step platform for the rapid determination of bevacizumab was constructed. This strategy has the advantages of being simple, fast and label-free. Because of the design and screening of the hairpin DNA, as well as the optimization of the concentration and electrochemical parameters, a low detection limit of 0.37 pM (0.054 ng mL-1) with a wide linear range (1 pM-1 µM) was obtained. Finally, the rationally constructed biosensor was successfully applied to the determination of bevacizumab in spiked samples, and it showed good accuracy and precision. This method is expected to truly realize accurate and rapid detection of bevacizumab and provides a new idea for the precise treatment of diseases.


Asunto(s)
Aptámeros de Nucleótidos , Técnicas Biosensibles , Bevacizumab , Técnicas Biosensibles/métodos , ADN , Sondas de ADN/genética , Límite de Detección , Técnicas Electroquímicas
5.
Orthod Craniofac Res ; 26(3): 491-499, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-36680384

RESUMEN

OBJECTIVES: To develop an artificial intelligence (AI) system for automatic palate segmentation through CBCT, and to determine the personalized available sites for palatal mini implants by measuring palatal bone and soft tissue thickness according to the AI-predicted results. MATERIALS AND METHODS: Eight thousand four hundred target slices (from 70 CBCT scans) from orthodontic patients were collected, labelled by well-trained orthodontists and randomly divided into two groups: a training set and a test set. After the deep learning process, we evaluated the performance of our deep learning model with the mean Dice similarity coefficient (DSC), average symmetric surface distance (ASSD), sensitivity (SEN), positive predictive value (PPV) and mean thickness percentage error (MTPE). The pixel traversal method was proposed to measure the thickness of palatal bone and soft tissue, and to predict available sites for palatal orthodontic mini implants. Then, an example of available sites for palatal mini implants from the test set was mapped. RESULTS: The average DSC, ASSD, SEN, PPV and MTPE for the segmented palatal bone tissue were 0.831%, 1.122%, 0.876%, 0.815% and 6.70%, while that for the palatal soft tissue were 0.741%, 1.091%, 0.861%, 0.695% and 12.2%, respectively. Besides, an example of available sites for palatal mini implants was mapped according to predefined criteria. CONCLUSIONS: Our AI system showed high accuracy for palatal segmentation and thickness measurement, which is helpful for the determination of available sites and the design of a surgical guide for palatal orthodontic mini implants.


Asunto(s)
Implantes Dentales , Métodos de Anclaje en Ortodoncia , Tomografía Computarizada de Haz Cónico Espiral , Humanos , Inteligencia Artificial , Métodos de Anclaje en Ortodoncia/métodos , Hueso Paladar/diagnóstico por imagen , Tomografía Computarizada de Haz Cónico/métodos
6.
BMC Genomics ; 23(1): 137, 2022 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-35168556

RESUMEN

BACKGROUND: Wucai suffers from low temperature during the growth period, resulting in a decline in yield and poor quality. But the molecular mechanisms of cold tolerance in wucai are still unclear. RESULTS: According to the phenotypes and physiological indexes, we screened out the cold-tolerant genotype "W18" (named CT) and cold-sensitive genotype "Sw-1" (named CS) in six wucai genotypes. We performed transcriptomic analysis using seedling leaves after 24 h of cold treatment. A total of 3536 and 3887 differentially expressed genes (DEGs) were identified between the low temperature (LT) and control (NT) comparative transcriptome in CT and CS, respectively, with 1690 DEGs specific to CT. The gene ontology (GO) analysis showed that the response to cadmium ion (GO:0,046,686), response to jasmonic acid (GO:0,009,753), and response to wounding (GO:0,009,611) were enriched in CT (LT vs NT). The DEGs were enriched in starch and sucrose metabolism and glutathione metabolism in both groups, and α-linolenic acid metabolism was enriched only in CT (LT vs NT). DEGs in these processes, including glutathione S-transferases (GSTs), 13S lipoxygenase (LOX), and jasmonate ZIM-domain (JAZ), as well as transcription factors (TFs), such as the ethylene-responsive transcription factor 53 (ERF53), basic helix-loop-helix 92 (bHLH92), WRKY53, and WRKY54.We hypothesize that these genes play important roles in the response to cold stress in this species. CONCLUSIONS: Our data for wucai is consistent with previous studies that suggest starch and sucrose metabolism increased the content of osmotic substances, and the glutathione metabolism pathway enhance the active oxygen scavenging. These two pathways may participated in response to cold stress. In addition, the activation of α-linolenic acid metabolism may promote the synthesis of methyl jasmonate (MeJA), which might also play a role in the cold tolerance of wucai.


Asunto(s)
Brassica , Respuesta al Choque por Frío , Brassica/genética , Frío , Respuesta al Choque por Frío/genética , Perfilación de la Expresión Génica , Regulación de la Expresión Génica de las Plantas , Estrés Fisiológico/genética , Transcriptoma
7.
Tumour Biol ; 39(6): 1010428317699131, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28618924

RESUMEN

The limited efficacy of conventional therapies for pancreatic ductal adenocarcinoma has led to the growing interest for identifying potential antigenic targets for immunotherapy. Placenta-specific 1 (PLAC1) is a new member of cancer-testis antigens with restricted expression in normal tissues. Ectopic activation of PLAC1 has been found in different types of cancers, but its role in pancreatic ductal adenocarcinoma remains unknown. This study evaluated the protein expression of PLAC1 and its clinical significance in pancreatic ductal adenocarcinoma. We examined PLAC1 expression in 93 pancreatic ductal adenocarcinoma samples by immunohistochemistry. The expression of PLAC1 was detected in 41 (44.1%) patients. Among patients' clinicopathological characteristics, PLAC1 expression was only significantly correlated with tumor differentiation (p = 0.028). Univariate analysis revealed that PLAC1 expression (p = 0.016) and tumor differentiation (p = 0.003) were significantly correlated with poor survival in the whole cohort. Subgroup analysis showed that PLAC1 expression was an independent prognostic biomarker in the perineural invasion positive subgroup (p < 0.05). This study demonstrated that the protein expression of PLAC1 was significantly associated with decreased overall survival in patients with pancreatic ductal adenocarcinoma, indicating that it was a valuable prognostic marker for pancreatic ductal adenocarcinoma and might be a potential target for immunotherapy.


Asunto(s)
Adenocarcinoma/genética , Biomarcadores de Tumor/genética , Carcinoma Ductal Pancreático/genética , Proteínas Gestacionales/genética , Adenocarcinoma/patología , Adulto , Anciano , Biomarcadores de Tumor/biosíntesis , Carcinoma Ductal Pancreático/patología , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Inmunoterapia , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Placenta/patología , Embarazo , Proteínas Gestacionales/biosíntesis , Pronóstico , Análisis de Supervivencia
8.
Infect Immun ; 84(5): 1387-1402, 2016 05.
Artículo en Inglés | MEDLINE | ID: mdl-26902724

RESUMEN

Francisella tularensis is the causative agent of tularemia and a category A potential agent of bioterrorism, but the pathogenic mechanisms of F. tularensis are largely unknown. Our previous transposon mutagenesis screen identified 95 lung infectivity-associated F. tularensis genes, including those encoding the Lon and ClpP proteases. The present study validates the importance of Lon and ClpP in intramacrophage growth and infection of the mammalian host by using unmarked deletion mutants of the F. tularensis live vaccine strain (LVS). Further experiments revealed that lon and clpP are also required for F. tularensis tolerance to stressful conditions. A quantitative proteomic comparison between heat-stressed LVS and the isogenic Lon-deficient mutant identified 29 putative Lon substrate proteins. The follow-up protein degradation experiments identified five substrates of the F. tularensis Lon protease (FTL578, FTL663, FTL1217, FTL1228, and FTL1957). FTL578 (ornithine cyclodeaminase), FTL663 (heat shock protein), and FTL1228 (iron-sulfur activator complex subunit SufD) have been previously described as virulence-associated factors in F. tularensis Identification of these Lon substrates has thus provided important clues for further understanding of the F. tularensis stress response and pathogenesis. The high-throughput approach developed in this study can be used for systematic identification of the Lon substrates in other prokaryotic and eukaryotic organisms.


Asunto(s)
Endopeptidasa Clp/metabolismo , Francisella tularensis/enzimología , Francisella tularensis/fisiología , Proteasa La/metabolismo , Estrés Fisiológico , Tularemia/microbiología , Factores de Virulencia/metabolismo , Animales , Línea Celular , Modelos Animales de Enfermedad , Endopeptidasa Clp/genética , Femenino , Francisella tularensis/genética , Eliminación de Gen , Sitios Genéticos , Humanos , Macrófagos/microbiología , Ratones Endogámicos BALB C , Proteasa La/genética , Tularemia/patología , Factores de Virulencia/genética
9.
Anal Sci ; 40(1): 85-91, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37843729

RESUMEN

Rapid and effective separation of nucleotides (NTs) and their derivatives is crucial for studying their physiological functions. In this work, we comprehensively evaluated the separation ability of a zwitterionic hydrophilic monolith, i.e., poly(N,N-dimethyl-N-(3-methacrylamidopropyl)-N-(3-sulfopropyl)ammonium betaine-co-N,N'-methylenebisacrylamide) (poly(SPP-co-MBA)) for NTs analysis, including its selectivity, chemical stability under extremely basic condition and compatibility with hydrophilic interaction liquid chromatography (HILIC) coupled with mass spectrometry (HILIC-MS). The poly(SPP-co-MBA) monolith exhibited excellent chemical stability, as evidenced by the low relative standard deviation of retention time (0.16-1.05%) after 4000 consecutive injections over one month under strong alkaline elution condition (pH 10). After optimizing the separation conditions, including buffer pH and concentration, organic solvent content and column temperature, four nucleoside triphosphates, five nucleoside diphosphates and five nucleoside monophosphates were baseline separated within 7 min. Additionally, the mixtures containing one nucleoside and its corresponding mono-, di-, and triphosphates were baseline separated within only 3 min, respectively. It is good HILIC-MS compatibility was also confirmed by the satisfactory peak shape and high response of nine NTs. Overall, the proposed poly(SPP-co-MBA) monolith exhibited good mechanical stability and compatibility of HILIC-MS, making it a promising technique for NTs analysis.


Asunto(s)
Nucleósidos , Nucleótidos , Nucleótidos/análisis , Nucleósidos/análisis , Nucleósidos/química , Cromatografía Liquida/métodos , Betaína/química , Interacciones Hidrofóbicas e Hidrofílicas
10.
Arthritis Res Ther ; 26(1): 96, 2024 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-38711064

RESUMEN

BACKGROUND: Gout is caused by monosodium urate (MSU) crystals deposition to trigger immune response. A recent study suggested that inhibition of Class I Histone deacetylases (HDACs) can significantly reduce MSU crystals-induced inflammation. However, which one of HDACs members in response to MSU crystals was still unknown. Here, we investigated the roles of HDAC3 in MSU crystals-induced gouty inflammation. METHODS: Macrophage specific HDAC3 knockout (KO) mice were used to investigate inflammatory profiles of gout in mouse models in vivo, including ankle arthritis, foot pad arthritis and subcutaneous air pouch model. In the in vitro experiments, bone marrow-derived macrophages (BMDMs) from mice were treated with MSU crystals to assess cytokines, potential target gene and protein. RESULTS: Deficiency of HDAC3 in macrophage not only reduced MSU-induced foot pad and ankle joint swelling but also decreased neutrophils trafficking and IL-1ß release in air pouch models. In addition, the levels of inflammatory genes related to TLR2/4/NF-κB/IL-6/STAT3 signaling pathway were significantly decreased in BMDMs from HDAC3 KO mice after MSU treatment. Moreover, RGFP966, selective inhibitor of HDAC3, inhibited IL-6 and TNF-α production in BMDMs treated with MSU crystals. Besides, HDAC3 deficiency shifted gene expression from pro-inflammatory macrophage (M1) to anti-inflammatory macrophage (M2) in BMDMs after MSU challenge. CONCLUSIONS: Deficiency of HDAC3 in macrophage alleviates MSU crystals-induced gouty inflammation through inhibition of TLR2/4 driven IL-6/STAT3 signaling pathway, suggesting that HDAC3 could contribute to a potential therapeutic target of gout.


Asunto(s)
Acrilamidas , Gota , Histona Desacetilasas , Macrófagos , Ratones Endogámicos C57BL , Ratones Noqueados , Fenilendiaminas , Ácido Úrico , Animales , Ácido Úrico/toxicidad , Histona Desacetilasas/metabolismo , Histona Desacetilasas/genética , Histona Desacetilasas/deficiencia , Macrófagos/metabolismo , Macrófagos/efectos de los fármacos , Gota/metabolismo , Gota/patología , Ratones , Inflamación/metabolismo , Inflamación/inducido químicamente , Masculino , Artritis Gotosa/inducido químicamente , Artritis Gotosa/metabolismo , Artritis Gotosa/patología , Modelos Animales de Enfermedad , Transducción de Señal/efectos de los fármacos
11.
Adv Clin Exp Med ; 2024 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-38506417

RESUMEN

BACKGROUND: Oxidative damage plays an important role in the progression of rheumatoid arthritis (RA). Emerging research evidence suggests that natural antioxidants may effectively ameliorate this disease. OBJECTIVES: To investigate the therapeutic effect of echinacoside (ECH) in a collagen-induced arthritis (CIA) mouse model and thus elucidate the underlying molecular mechanism in RA. MATERIAL AND METHODS: Collagen-induced arthritis mice were intraperitoneally administered 1% dimethyl sulfoxide (DMSO) (control) or 0.6 mg of ECH every other day for 1 month. Arthritis scores and the number of affected paws were assessed. On day 60, mice were euthanized, synovial tissue specimens were obtained, and serum interleukin (IL)-6 and IL-1â expression levels were measured. Mitochondrial morphologies, reactive oxygen species (ROS) content, expression of dynamin-related protein 1 (Drp1), IL-6, nod-like receptor protein 3 (NLRP3), kelch-like ECH-associated protein 1 (Keap1), and nuclear factor-erythroid-2-related factor 2 (Nrf2) contents in synovium were analyzed and compared between DMSOand ECH-treated CIA mice. RESULTS: Following ECH treatment, mitochondria of CIA-induced mice were found to be elongated, while their arthritis scores, inflammation and the number of affected paws, and the expression levels of Drp1, NLRP3, IL-6, ROS, and Keap1 were all found to be significantly reduced. Conversely, the level of antioxidant factor Nrf2 was found to be elevated. Further, mitochondrial fission was found to be inhibited in synovial tissues. CONCLUSIONS: Our findings validate the therapeutic efficacy of ECH in the CIA mouse model. Echinacoside may suppress oxidative stress and inhibit inflammation by regulating the Nrf2/Drp1 pathway, thus supporting its utility in the treatment of RA.

12.
Phytomedicine ; 128: 155589, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38608487

RESUMEN

BACKGROUND: Food products undergo a pronounced Maillard reaction (MR) during the cooking process, leading to the generation of substantial quantities of Maillard reaction products (MRPs). Within this category, advanced glycation end products (AGEs), acrylamide (AA), and heterocyclic amines (HAs) have been implicated as potential risk factors associated with the development of diseases. PURPOSE: To explore the effects of polyphenols, a class of bioactive compounds found in plants, on the inhibition of MRPs and related diseases. Previous research has mainly focused on their interactions with proteins and their effects on the gastrointestinal tract and other diseases, while fewer studies have examined their inhibitory effects on MRPs. The aim is to offer a scientific reference for future research investigating the inhibitory role of polyphenols in the MR. METHODS: The databases PubMed, Embase, Web of Science and The Cochrane Library were searched for appropriate research. RESULTS: Polyphenols have the potential to inhibit the formation of harmful MRPs and prevent related diseases. The inhibition of MRPs by polyphenols primarily occurs through the following mechanisms: trapping α-dicarbonyl compounds, scavenging free radicals, chelating metal ions, and preserving protein structure. Simultaneously, polyphenols exhibit the ability to impede the onset and progression of related diseases such as diabetes, atherosclerosis, cancer, and Alzheimer's disease through diverse pathways. CONCLUSION: This review presents that inhibition of polyphenols on Maillard reaction products and their induction of related diseases. Further research is imperative to enhance our comprehension of additional pathways affected by polyphenols and to fully uncover their potential application value in inhibiting MRPs.


Asunto(s)
Productos Finales de Glicación Avanzada , Reacción de Maillard , Polifenoles , Polifenoles/farmacología , Polifenoles/química , Productos Finales de Glicación Avanzada/antagonistas & inhibidores , Humanos , Acrilamida/química , Enfermedad de Alzheimer/tratamiento farmacológico , Neoplasias/tratamiento farmacológico , Aterosclerosis/tratamiento farmacológico , Aterosclerosis/prevención & control , Animales
13.
bioRxiv ; 2024 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-38645023

RESUMEN

The Legionella pneumophila Sde family of translocated proteins promotes host tubular endoplasmic reticulum (ER) rearrangements that are tightly linked to phosphoribosyl-ubiquitin (pR-Ub) modification of Reticulon 4 (Rtn4). Sde proteins have two additional activities of unclear relevance to the infection process: K63 linkage-specific deubiquitination and phosphoribosyl modification of polyubiquitin (pR-Ub). We show here that the deubiquitination activity (DUB) stimulates ER rearrangements while pR-Ub protects the replication vacuole from cytosolic surveillance by autophagy. Loss of DUB activity was tightly linked to lowered pR-Ub modification of Rtn4, consistent with the DUB activity fueling the production of pR-Ub-Rtn4. In parallel, phosphoribosyl modification of polyUb, in a region of the protein known as the isoleucine patch, prevented binding by the autophagy adapter p62. An inability of Sde mutants to modify polyUb resulted in immediate p62 association, a critical precursor to autophagic attack. The ability of Sde WT to block p62 association decayed quickly after bacterial infection, as predicted by the presence of previously characterized L. pneumophila effectors that inactivate Sde and remove polyUb. In sum, these results show that the accessory Sde activities act to stimulate ER rearrangements and protect from host innate immune sensing in a temporal fashion.

14.
Stem Cell Res ; 76: 103326, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38324932

RESUMEN

Hoxb5 exhibits preferential expression in hematopoietic stem cells (HSCs) and uniquely marks the long-term HSCs (LT-HSCs). Previous studies have demonstrated the remarkable capability of Hoxb5 to alter cell fates when enforced expression in blood progenitors, such as B cell progenitors and multipotent progenitors. Additionally, Hoxb5 deficiency does not hinder the generation of LT-HSCs. However, the specific impact of Hoxb5 deletion on LT-HSCs has remained unexplored. To address this, we developed a conditional Hoxb5 knockout-reporter mouse model, wherein Hoxb5 was knock out by the Vav-cre recombinase, and the endogenous Hoxb5 promoter drove the expression of the blue fluorescent protein (BFP). Our findings revealed that the primary recipients, who transplanted with HSCs indicating Hoxb5 deficiency by the presence of BFP (BFP-positive HSCs), exhibited comparable levels of donor chimerism and lineage chimerism to recipients transplanted with HSCs that spontaneously did not express Hoxb5 and thus lacked BFP expression (BFP-negative HSCs). However, during the secondary transplantation, recipients receiving total bone marrow (BM) from the primary recipients with BFP-positive HSCs showed significantly higher levels of donor chimerism and more robust multi-lineage chimerism compared to those receiving total BM from the primary recipients with BFP-negative HSCs. Our results indicate that deleting Hoxb5 in LT-HSCs transiently influences their lineage differentiation bias without compromising their long-term self-renewal capacity. These findings highlight the primary role of Hoxb5 in regulating lineage commitment decisions in LT-HSCs, while emphasizing that its presence is not indispensable for the maintenance of long-term self-renewal capacity.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Factores de Transcripción , Animales , Ratones , Médula Ósea , Diferenciación Celular/fisiología , Células Madre Hematopoyéticas/metabolismo , Proteínas de Homeodominio/genética , Proteínas de Homeodominio/metabolismo , Ratones Noqueados , Factores de Transcripción/genética , Factores de Transcripción/metabolismo
15.
Cell Prolif ; : e13683, 2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38830795

RESUMEN

Chimeric antigen receptor-natural killer (CAR-NK) cell therapy is emerging as a promising cancer treatment, with notable safety and source diversity benefits over CAR-T cells. This study focused on optimizing CAR constructs for NK cells to maximize their therapeutic potential. We designed seven CD19 CAR constructs and expressed them in NK cells using a retroviral system, assessing their tumour-killing efficacy and persistence. Results showed all constructs enhanced tumour-killing and prolonged survival in tumour-bearing mice. In particular, CAR1 (CD8 TMD-CD3ζ SD)-NK cells showed superior efficacy in treating tumour-bearing animals and exhibited enhanced persistence when combined with OX40 co-stimulatory domain. Of note, CAR1-NK cells were most effective at lower effector-to-target ratios, while CAR4 (CD8 TMD-OX40 CD- FcεRIγ SD) compromised NK cell expansion ability. Superior survival rates were noted in mice treated with CAR1-, CAR2 (CD8 TMD- FcεRIγ SD)-, CAR3 (CD8 TMD-OX40 CD- CD3ζ SD)- and CAR4-NK cells over those treated with CAR5 (CD28 TMD- FcεRIγ SD)-, CAR6 (CD8 TMD-4-1BB CD-CD3ζ 1-ITAM SD)- and CAR7 (CD8 TMD-OX40 CD-CD3ζ 1-ITAM SD)-NK cells, with CAR5-NK cells showing the weakest anti-tumour activity. Increased expression of exhaustion markers, especially in CAR7-NK cells, suggests that combining CAR-NK cells with immune checkpoint inhibitors might improve anti-tumour outcomes. These findings provide crucial insights for developing CAR-NK cell products for clinical applications.

16.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 33(10): 1323-7, 2013 Oct.
Artículo en Zh | MEDLINE | ID: mdl-24432672

RESUMEN

OBJECTIVE: To understand the difference in clinical indicators of gout patients of different Chinese medical syndromes and its clinical significance. METHODS: Form November 2011 to December 2012, syndrome typed were 257 male gout in-/outpatients from Affiliated Hospital of Chuanbei Medical College. Another 50 healthy male subjects were recruited as the control. Their clinical and laboratory data were collected. All were excluded from infections and other inflammatory diseases. RESULTS: Four syndrome types existed in gout patients, i.e., intermingled phlegm-stasis blood syndrome (IPSBS), obstruction of dampness and heat syndrome (ODHS), Pi-deficiency induced dampness syndrome (PDIDS), qi-blood deficiency syndrome (QBDS). Of them, 53 acute phase gout patients suffered from IPSBS, 41 from ODHS, 25 from QBDS, and 17 from PDIDS; 41 non-acute phase gout patients suffered from QBDS, 40 from PDIDS, 24 from ODHS, and 16 from IPSBS. Statistical analysis of clinical data showed that, when compared with the normal control group, there was statistical difference in blood routines (WBC, GR, LY, MO) and blood biochemical indices (UA, Ur, Cr, ALT, AST, ALB, GLOB, TG, HDL-C, VLDL-C, apoA, apoB100) of gout patients of different syndromes (P < 0.05, P < 0.01). There was also statistical difference or correlation among different syndromes (P < 0.05). CONCLUSIONS: In the acute phase gout patients, IPSBS and ODHS were dominated, while in the non-acute phase gout patients, QBDS and PDIDS were often seen. In patients of IPSBS and ODHS, inflammation and immune response were more obvious, indicating that better efficacy might be achieved by clearing heat and removing blood stasis associated anti-inflammatory and immune regulation therapies. In patients of QBDS and PDIDS, impaired renal functions were more significant, indicating that better efficacy might be achieved by invigorating Pi and tonifying Shen dominated treatment.


Asunto(s)
Gota/diagnóstico , Medicina Tradicional China/métodos , Adulto , Anciano , Estudios de Casos y Controles , Humanos , Masculino , Persona de Mediana Edad , Deficiencia Yang/diagnóstico , Deficiencia Yin/diagnóstico , Adulto Joven
17.
Biomedicines ; 11(12)2023 Dec 07.
Artículo en Inglés | MEDLINE | ID: mdl-38137461

RESUMEN

Radiotherapy, a treatment method employing radiation to eradicate tumor cells and subsequently reduce or eliminate tumor masses, is widely applied in the management of numerous patients with tumors. However, its therapeutic effectiveness is somewhat constrained by various drug-resistant factors. Recent studies have highlighted the ubiquitination/deubiquitination system, a reversible molecular modification pathway, for its dual role in influencing tumor behaviors. It can either promote or inhibit tumor progression, impacting tumor proliferation, migration, invasion, and associated therapeutic resistance. Consequently, delving into the potential mechanisms through which ubiquitination and deubiquitination systems modulate the response to radiotherapy in malignant tumors holds paramount significance in augmenting its efficacy. In this paper, we comprehensively examine the strides made in research and the pertinent mechanisms of ubiquitination and deubiquitination systems in governing radiotherapy resistance in tumors. This underscores the potential for developing diverse radiosensitizers targeting distinct mechanisms, with the aim of enhancing the effectiveness of radiotherapy.

18.
Nanomicro Lett ; 15(1): 135, 2023 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-37221393

RESUMEN

Lithium-ion batteries (LIBs) have helped revolutionize the modern world and are now advancing the alternative energy field. Several technical challenges are associated with LIBs, such as increasing their energy density, improving their safety, and prolonging their lifespan. Pressed by these issues, researchers are striving to find effective solutions and new materials for next-generation LIBs. Polymers play a more and more important role in satisfying the ever-increasing requirements for LIBs. Polyimides (PIs), a special functional polymer, possess unparalleled advantages, such as excellent mechanical strength, extremely high thermal stability, and excellent chemical inertness; they are a promising material for LIBs. Herein, we discuss the current applications of PIs in LIBs, including coatings, separators, binders, solid-state polymer electrolytes, and active storage materials, to improve high-voltage performance, safety, cyclability, flexibility, and sustainability. Existing technical challenges are described, and strategies for solving current issues are proposed. Finally, potential directions for implementing PIs in LIBs are outlined.

19.
PeerJ ; 11: e15010, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36949758

RESUMEN

Purpose: To quantitatively assess and compare the clinical outcomes, including survival rate, success rate, and peri-implant indices of titanium and zirconium implants in randomized controlled trials. Methods: The electronic databases searched included the Cochrane Central Register of Controlled Trials (CENTRAL), Medline via Ovid, EMBASE, and Web of Science. Randomized controlled trials (RCTs) that reported the effects of zirconium implants on primary outcomes, such as survival rate, success rate, marginal bone loss (MBL), and probing pocket depth (PPD), compared to titanium implants were included in this review. Two reviewers independently screened and selected the records, assessed their quality, and extracted the data from the included studies. Results: A total of four studies from six publications reviewed were included. Two of the comparative studies were assessed at minimal risk of bias. Zirconium implants may have a lower survival rate (risk ratio (RR) = 0.91, CI [0.82-1.02], P = 0.100, I 2 = 0%) and a significantly lower success rate than titanium implants (RR = 0.87, CI [0.78-0.98], P = 0.030, I 2 = 0%). In addition, there was no difference between the titanium and zirconium implants in terms of MBL, PPD, bleeding on probing (BOP), plaque index (PI), and pink esthetic score (PES) (for MBL, MD = 0.25, CI [0.02-0.49], P = 0.033, I 2 = 0%; for PPD, MD = -0.07, CI [-0.19-0.05], P = 0.250, I 2 = 31%). Conclusion: Zirconium implants may have higher failure rates due to their mechanical weakness. Zirconium implants should be strictly assessed before they enter the market. Further studies are required to confirm these findings.


Asunto(s)
Titanio , Circonio , Titanio/efectos adversos , Ensayos Clínicos Controlados Aleatorios como Asunto , Prótesis e Implantes , Tasa de Supervivencia
20.
J Phys Chem Lett ; 14(42): 9403-9411, 2023 Oct 26.
Artículo en Inglés | MEDLINE | ID: mdl-37823837

RESUMEN

Symmetric solid oxide electrolysis cells (SSOECs) have garnered significant scientific interest due to their simplified cell architecture, robust operational reliability, and cost-effectiveness, for which a highly electrocatalytically active electrode is the decisive main factor. This work evaluates the electrochemical performance of Ni-doped Pr0.5Ba0.5FeO3-δ (PBF) perovskite materials, with a focus on Pr0.5Ba0.5Fe0.8Ni0.2O3-δ (PBFN). The experimental findings herein prove the exceptional electrocatalytic ability of PBFN in facilitating the oxygen evolution and carbon dioxide reduction reaction, surpassing the electrochemical performance of PBF. In addition, the PBFN symmetric cell has excellent performance for CO2 electrolysis, and the cell has a low polarization resistance value of 0.1 Ω·cm2. Moreover, it achieves an impressive current density value of 1.118 A·cm-2 under operating conditions of 2.0 V and 800 °C, which is superior to those of the PBF symmetric cell and the PBFN asymmetric cell. It also has a good structural and performance stability. These results imply a bright development prospect of PBFN as electrodes for SSOECs.

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