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1.
Mol Cancer ; 23(1): 120, 2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38831402

RESUMEN

The efficacy of anthracycline-based chemotherapeutics, which include doxorubicin and its structural relatives daunorubicin and idarubicin, remains almost unmatched in oncology, despite a side effect profile including cumulative dose-dependent cardiotoxicity, therapy-related malignancies and infertility. Detoxifying anthracyclines while preserving their anti-neoplastic effects is arguably a major unmet need in modern oncology, as cardiovascular complications that limit anti-cancer treatment are a leading cause of morbidity and mortality among the 17 million cancer survivors in the U.S. In this study, we examined different clinically relevant anthracycline drugs for a series of features including mode of action (chromatin and DNA damage), bio-distribution, anti-tumor efficacy and cardiotoxicity in pre-clinical models and patients. The different anthracycline drugs have surprisingly individual efficacy and toxicity profiles. In particular, aclarubicin stands out in pre-clinical models and clinical studies, as it potently kills cancer cells, lacks cardiotoxicity, and can be safely administered even after the maximum cumulative dose of either doxorubicin or idarubicin has been reached. Retrospective analysis of aclarubicin used as second-line treatment for relapsed/refractory AML patients showed survival effects similar to its use in first line, leading to a notable 23% increase in 5-year overall survival compared to other intensive chemotherapies. Considering individual anthracyclines as distinct entities unveils new treatment options, such as the identification of aclarubicin, which significantly improves the survival outcomes of AML patients while mitigating the treatment-limiting side-effects. Building upon these findings, an international multicenter Phase III prospective study is prepared, to integrate aclarubicin into the treatment of relapsed/refractory AML patients.


Asunto(s)
Aclarubicina , Antraciclinas , Leucemia Mieloide Aguda , Humanos , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/mortalidad , Aclarubicina/farmacología , Aclarubicina/uso terapéutico , Antraciclinas/uso terapéutico , Antineoplásicos/uso terapéutico , Antineoplásicos/farmacología , Antineoplásicos/efectos adversos , Animales , Femenino , Masculino , Resultado del Tratamiento
2.
Nanoscale Adv ; 6(11): 2945-2953, 2024 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-38817426

RESUMEN

Single-particle detection and sensing, powered by Förster resonance energy transfer (FRET), offers precise monitoring of molecular interactions and environmental stimuli at a nanometric resolution. Despite its potential, the widespread use of FRET has been curtailed by the rapid photobleaching of traditional fluorophores. This study presents a robust single-particle FRET platform utilizing upconversion nanoparticles (UCNPs), which stand out for their remarkable photostability, making them superior to conventional organic donors for energy transfer-based assays. Our comprehensive research demonstrates the influence of UCNPs' size, architecture, and dye selection on the efficiency of FRET. We discovered that small particles (∼14 nm) with a Yb3+-enriched outermost shell exhibit a significant boost in FRET efficiency, a benefit not observed in larger particles (∼25 nm). 25 nm UCNPs with an inert NaLuF4 shell demonstrated a comparable level of emission enhancement via FRET as those with a Yb3+-enriched outermost shell. At the single-particle level, these FRET-enhanced UCNPs manifested an upconversion green emission intensity that was 8.3 times greater than that of their unmodified counterparts, while maintaining notable luminescence stability. Our upconversion FRET system opens up new possibilities for developing more effective high-brightness, high-sensitivity single-particle detection, and sensing modalities.

3.
Nano Lett ; 2024 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-38588010

RESUMEN

Hampered by their susceptibility to nucleophilic attack and chemical bleaching, electron-deficient squaraine dyes have long been considered unsuitable for biological imaging. This study unveils a surprising twist: in aqueous environments, bleaching is not irreversible but rather a reversible spontaneous quenching process. Leveraging this new discovery, we introduce a novel deep-red squaraine probe tailored for live-cell super-resolution imaging. This probe enables single-molecule localization microscopy (SMLM) under physiological conditions without harmful additives or intense lasers and exhibits spontaneous blinking orchestrated by biological nucleophiles, such as glutathione or hydroxide anion. With a low duty cycle (∼0.1%) and high-emission rate (∼6 × 104 photons/s under 400 W/cm2), the squaraine probe surpasses the benchmark Cy5 dye by 4-fold and Si-rhodamine by a factor of 1.7 times. Live-cell SMLM with the probe reveals intricate structural details of cell membranes, which demonstrates the high potential of squaraine dyes for next-generation super-resolution imaging.

4.
J Int Med Res ; 52(3): 3000605241234558, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38518198

RESUMEN

OBJECTIVE: To investigate the roles and underlying mechanisms of vascular endothelial growth factor receptor-3 (VEGFR-3) in gastric cancer (GC). METHODS: VEGFR-3 gene expression profiles in human gastric adenocarcinoma (GAC) tissues were analysed using The Cancer Genome Atlas database. Human GC cell lines and were used for in vitro studies. Mouse models of GC and distant metastasis were used for in vivo studies. Silencing of VEGFR-3 gene expression was achieved using small interfering RNA. RESULTS: VEGFR-3 gene expression was significantly elevated in GAC tissues and GC cells. Higher VEGFR-3 expression was positively correlated with more advanced stages and a greater number of metastatic lymph nodes. In vitro studies in GC cells showed that knockdown of VEGFR-3 gene expression significantly suppressed cell proliferation and migration, but promoted apoptosis. In vivo investigations revealed that silencing of VEGFR-3 gene expression exhibited significant inhibition on tumour growth and metastasis. Further mechanistic studies showed that VEGFR-3 exerted its pathological roles by affecting the key molecules in the apoptotic and epithelial-mesenchymal transition pathways. CONCLUSION: The molecular pathways associated with VEGFR-3-mediated pathological effects could be targets in the development of novel approaches for the diagnosis, prognosis and treatment of GC.


Asunto(s)
Neoplasias Gástricas , Receptor 3 de Factores de Crecimiento Endotelial Vascular , Animales , Humanos , Ratones , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Invasividad Neoplásica/genética , Pronóstico , Neoplasias Gástricas/patología , Factor A de Crecimiento Endotelial Vascular/metabolismo , Receptor 2 de Factores de Crecimiento Endotelial Vascular/genética , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismo , Receptor 2 de Factores de Crecimiento Endotelial Vascular/farmacología , Receptor 3 de Factores de Crecimiento Endotelial Vascular/genética
5.
Cell Death Discov ; 10(1): 138, 2024 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-38485945

RESUMEN

Triple-negative breast cancer (TNBC) is a pathological subtype of breast cancer (BC) with high malignancy, strong invasiveness and poor prognosis. Long non-coding RNA (LncRNA) plays an important role during tumorigenesis. We identified that Linc00707 was upregulated in TNBC tissues by TCGA database and RT-qPCR assay, compared with normal breast tissues and other subtypes of BC. Linc00707 promoted TNBC cells proliferation, migration and invasion. Furthermore, we found that knockdown of Linc00707 influenced autophagy via PI3K/AKT/mTOR signaling pathway in TNBC cells. Linc00707 affected the progress of TNBC cells through affecting autophagy. Further mechanistic experiments confirmed that Linc00707 could competitively bind with miR-423-5p to up-regulate MARCH2 expression, ultimately promoting TNBC progression and autophagy through PI3K/AKT/mTOR pathway. In conclusion, we demonstrate that Linc00707 is a key molecule in tumor progression and may be an effective target for patients with TNBC.

6.
Cancer Res ; 84(10): 1583-1596, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38417135

RESUMEN

Patients with primary refractory acute myeloid leukemia (AML) have a dismal long-term prognosis. Elucidating the resistance mechanisms to induction chemotherapy could help identify strategies to improve AML patient outcomes. Herein, we retrospectively analyzed the multiomics data of more than 1,500 AML cases and found that patients with spliceosome mutations had a higher risk of developing refractory disease. RNA splicing analysis revealed that the mis-spliced genes in refractory patients converged on translation-associated pathways, promoted mainly by U2AF1 mutations. Integrative analyses of binding and splicing in AML cell lines substantiated that the splicing perturbations of mRNA translation genes originated from both the loss and gain of mutant U2AF1 binding. In particular, the U2AF1S34F and U2AF1Q157R mutants orchestrated the inclusion of exon 11 (encoding a premature termination codon) in the eukaryotic translation initiation factor 4A2 (EIF4A2). This aberrant inclusion led to reduced eIF4A2 protein expression via nonsense-mediated mRNA decay. Consequently, U2AF1 mutations caused a net decrease in global mRNA translation that induced the integrated stress response (ISR) in AML cells, which was confirmed by single-cell RNA sequencing. The induction of ISR enhanced the ability of AML cells to respond and adapt to stress, contributing to chemoresistance. A pharmacologic inhibitor of ISR, ISRIB, sensitized U2AF1 mutant cells to chemotherapy. These findings highlight a resistance mechanism by which U2AF1 mutations drive chemoresistance and provide a therapeutic approach for AML through targeting the ISR pathway. SIGNIFICANCE: U2AF1 mutations induce the integrated stress response by disrupting splicing of mRNA translation genes that improves AML cell fitness to enable resistance to chemotherapy, which can be targeted to improve AML treatment.


Asunto(s)
Resistencia a Antineoplásicos , Leucemia Mieloide Aguda , Mutación , Factor de Empalme U2AF , Humanos , Factor de Empalme U2AF/genética , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/patología , Resistencia a Antineoplásicos/genética , Biosíntesis de Proteínas/efectos de los fármacos , ARN Mensajero/genética , Empalme del ARN/genética , Animales , Estudios Retrospectivos , Ratones , Línea Celular Tumoral , Factor 4A Eucariótico de Iniciación/genética , Factor 4A Eucariótico de Iniciación/metabolismo
7.
Small ; : e2309035, 2024 Jan 17.
Artículo en Inglés | MEDLINE | ID: mdl-38234137

RESUMEN

Lanthanide-doped upconversion nanoparticles (UCNPs) hold promise for single-molecule imaging owing to their excellent photostability and minimal autofluorescence. However, their limited water dispersibility, often from the hydrophobic oleic acid ligand during synthesis, is a challenge. To address this, various surface modification strategies' impact on single-particle upconversion luminescence are studied. UCNPs are made hydrophilic through methods like ligand exchange with dye IR806, HCl or NOBF4 treatment, silica coating (SiO2 or mesoporous mSiO2 ), and self-assembly with polymer of DSPE-PEG or F127. The studies revealed that UCNPs modified with NOBF4 and DSPE-PEG exhibited notably higher single-particle brightness with minimal quenching (3% and 8%, respectively), followed by SiO2 , F127, IR806, mSiO2 , and HCl (84% quenching). HCl disrupted UCNPs's crystal lattice, weakening luminescence, while mSiO2 absorbed solvent molecules, causing luminescence quenching. Energy transfer to IR806 also reduced the brightness. Additionally, a prevalence of upconversion red emission over green is observed, with the red-to-green ratio increasing with irradiance. UCNPs coated with DSPE-PEG exhibited the brightest single-particle luminescence in water, retaining 48% of its original emission due to a lower critical micelle concentration and superior water protection. In summary, the investigation provides valuable insights into the role of surface chemistry on UCNPs at the single-particle level.

8.
Angew Chem Int Ed Engl ; 63(1): e202316192, 2024 Jan 02.
Artículo en Inglés | MEDLINE | ID: mdl-37975636

RESUMEN

Fluorescent probes are essential for single-molecule imaging. However, their application in biological systems is often limited by the short photobleaching lifetime. To overcome this, we developed a novel thiolation strategy for squaraine dyes. By introducing thiolation of the central cyclobutene of squaraine (thio-squaraine), we observed a ≈5-fold increase in photobleaching lifetime. Our single-molecule data analysis attributes this improvement to improved photostability resulting from thiolation. Interestingly, bulk measurements show rapid oxidation of thio-squaraine to its oxo-analogue under irradiation, giving the perception of inferior photostability. This discrepancy between bulk and single-molecule environments can be ascribed to the factors in the latter, including larger intermolecular distances and restricted mobility, which reduce the interactions between a fluorophore and reactive oxygen species produced by other fluorophores, ultimately impacting photobleaching and photoconversion rate. We demonstrate the remarkable performance of thio-squaraine probes in various imaging buffers, such as glucose oxidase with catalase (GLOX) and GLOX+trolox. We successfully employed these photostable probes for single-molecule tracking of CD56 membrane protein and monitoring mitochondria movements in live neurons. CD56 tracking revealed distinct motion states and the corresponding protein fractions. This investigation is expected to propel the development of single-molecule imaging probes, particularly in scenarios where bulk measurements show suboptimal performance.


Asunto(s)
Ciclobutanos , Colorantes Fluorescentes , Fotoblanqueo , Fenoles , Ionóforos
9.
Res Microbiol ; : 104152, 2023 Nov 11.
Artículo en Inglés | MEDLINE | ID: mdl-37952706

RESUMEN

Phytophthora sojae, one of the most devastating Oomycete pathogens, causes severe diseases that lead to economic loss in the soybean industry. The production of zoospores play a crucial role during the development of Phytophthora disease. In this work, CRISPR/Cas9 genome editing technology were used to obtain protein kinase A regulatory subunit (PsPkaR) knockout mutants. The role of PsPkaR in the production of zoospores and pathogenicity of P. sojae was analyzed. The overall findings indicate that PsPkaR is involved in regulating the growth process of P. sojae, primarily affecting the hyphal morphology and growth rate. Additionally, PsPkaR participates in the regulation of the release process of zoospores. Specifically, knocking-out PsPkaR resulted in incomplete cytoplasmic differentiation and uneven protoplast division, leading to abnormal release of zoospores. Furthermore, when the PsPkaR knockout mutants were inoculated on soybean leaves, the pathogenicity was significantly reduced compared to that of the wild-type and control strains. These findings of this study provide important clues and evidence regarding the role of the cAMP-PKA signaling pathway in the interaction between P. sojae and its host. This work contributes to a better understanding of the pathogenic mechanism of P. sojae and the development of corresponding prevention and control strategies.

10.
Sci Rep ; 13(1): 18608, 2023 10 30.
Artículo en Inglés | MEDLINE | ID: mdl-37903775

RESUMEN

A large number of studies indicate that Potassium Voltage-Gated Channel Q4 (KCNQ4) gene is the cause of non-syndromic hearing loss, but there are few studies investigating the role of KCNQ4 in cancers and scarcity of comprehensive analysis of its involvement in the diagnosis, methylation, mutation, prognosis of various cancer types. Therefore, the aim of this study is to examine the anticancerous and immune effects of KCNQ4 in various cancers and its potential value in breast cancer. In this study, we explored the potential role of KCNQ4 in cancers using public databases and the R software for bioinformatics analysis. The results showed that the low expression of KCNQ4 across specific cancer types was positively associated with low mutation frequency and methylation, and the improved survival. Eight small molecule compounds were identified that could potentially target KCNQ4. In addition, immunohistochemistry confirmed that the KCNQ4 expression was low in breast cancer. In vitro experiments confirmed that overexpression of KCNQ4 inhibited cell migration and invasion and promoted apoptosis. In summary, our comprehensive pan-cancer analysis highlights the potential of KCNQ4 as a cancer marker, and can be used as an auxiliary prognostic indicator and an indicator for immunotherapy in certain tumor types.


Asunto(s)
Neoplasias de la Mama , Sordera , Humanos , Femenino , Sordera/genética , Mutación , Neoplasias de la Mama/genética , Canales de Potasio KCNQ/genética
11.
PLoS One ; 18(10): e0292898, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37831731

RESUMEN

Lipoxygenase (LOX) gene plays an essential role in plant growth, development, and stress response. 15 LOX genes were identified, which were unevenly distributed on chromosomes and divided into three subclasses in this study. In promoter region analysis, many cis-elements were identified in growth and development, abiotic stress response, hormonal response, and light response. qRT-PCR showed that the LOX gene showed tissue specificity in seven tissues, especially XsLOX1, 3, and 7 were relatively highly expressed in roots, stems, and axillary buds. The different expression patterns of LOX genes in response to abiotic stress and hormone treatment indicate that different XsLOX genes have different reactions to these stresses and play diversified roles. This study improves our understanding of the mechanism of LOX regulation in plant growth, development, and stress and lays a foundation for further analysis of biological functions.


Asunto(s)
Lipooxigenasa , Estrés Fisiológico , Lipooxigenasa/genética , Lipooxigenasa/metabolismo , Estrés Fisiológico/genética , Regulación de la Expresión Génica de las Plantas , Filogenia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
12.
Adv Mater ; 35(51): e2304907, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37566538

RESUMEN

Dye-sensitization can enhance lanthanide-based upconversion luminescence, but is hindered by interfacial energy transfer from organic dye to lanthanide ion Yb3+ . To overcome these limitations, modifying coordination sites on dye conjugated structures and minimizing the distance between fluorescence cores and Yb3+ in upconversion nanoparticles (UCNPs) are proposed. The specially designed near-infrared (NIR) dye, disulfo-indocyanine green (disulfo-ICG), acts as the antenna molecule and exhibits a 2413-fold increase in luminescence under 808 nm excitation compared to UCNPs alone using 980 nm irradiation. The significant improvement is attributed to the high energy transfer efficiency of 72.1% from disulfo-ICG to Yb3+ in UCNPs, with majority of energy originating from triplet state (T1 ) of disulfo-ICG. Shortening the distance between the dye and lanthanide ions increases the probability of energy transfer and strengthens the heavy atom effect, leading to enhanced T1 generation and improved dye-triplet sensitization upconversion. Importantly, this approach also applies to 730 nm excitation Cy7-SO3 sensitization system, overcoming the spectral mismatch between Cy7 and Yb3+ and achieving a 52-fold enhancement in luminescence. Furthermore, the enhancement of upconversion at single particle level through dye-sensitization is demonstrated. This strategy expands the range of NIR dyes for sensitization and opens new avenues for highly efficient dye-sensitized upconversion systems.

13.
PeerJ ; 11: e15604, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37529209

RESUMEN

A detailed morphological description and comparative study were conducted on numerous large-sized hamster remains collected from the late Middle Pleistocene Locality 2 of Shanyangzhai (Syz 2), Hebei Province, China. The comparisons reveal that these fossils are highly similar to the extant Tscherskia triton in size and morphology, including the small degree of alternating between the main opposite cusps on M1-3, the presence of axioloph on M3, and mesolophids on m1-2 that are present but seldom reach the lingual margin of the teeth, among other features. However, minor differences between the two still exist. Consequently, all these fossils are designated as a chronosubspecies of the extant species, T. triton varians comb. nov. The skull and molar morphologies of Cricetinus varians and T. triton were meticulously compared to resolve the long-standing debate regarding the validity of Cricetinus Zdansky, 1928 and C. varians Zdansky, 1928. The findings indicate that the differences between the two are slight; as a result, C. varians can only be considered a chronosubspecies of T. triton, i.e., T. triton varians comb. nov., and Cricetinus should be recognized as a junior synonym of Tscherskia. We tentatively propose that, among the seven species once referred to Cricetinus, C. europaeus, C. gritzai, C. janossyi, and C. koufosi should be reassigned to Tscherskia, while C. beremendensis should be transferred to Allocricetus, and C. mesolophidos to Neocricetodon. Excluding Tscherskia sp. from the Late Pliocene Youhe fauna, there are no reliable Tscherskia fossils in China earlier than the Middle Pleistocene. Based on the current evidence, Tscherskia may have originated from Neocricetodon during the Early Pliocene in Europe and subsequently spread to Asia. T. triton is its sole surviving representative, which now exclusively inhabits East Asia.


Asunto(s)
Roedores , Diente , Cricetinae , Animales , Fósiles , Arvicolinae , China
14.
PeerJ ; 11: e15738, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37483974

RESUMEN

Background: Leaf nutrient resorption is a key strategy in plant conservation that minimizes nutrient loss and enhances productivity. However, the differences of the nutrient resorption among garden tree species in urban ecosystems were not clearly understood, especially the differences of nitrogen resorption efficiency (NRE) and phosphorous resorption efficiency (PRE) between evergreen and deciduous trees. Methods: We selected 40 most generally used garden tree specie belonged two life forms (evergreen and deciduous) and investigated the nitrogen (N) and phosphorus (P) concentrations in green and senesced leaves and soil nutrient concentrations of nine samples trees for each species. Then, the nutrient concentrations and resorption efficiency were compared, and the soil nutrients utilization strategies were further analyzed. Results: The results showed that the N concentration was significantly higher in the green and senesced leaves of deciduous trees than in the leaves of evergreen trees. The two life-form trees were both N limited and evergreen trees were more sensitive to N limitation. The NRE and PRE in the deciduous trees were significantly higher than those in the evergreen trees. The NRE was significantly positively correlated with the PRE in the deciduous trees. As the soil N and P concentrations increased, the nutrient resorption efficiency (NuRE) of the evergreen trees increased, but that of the deciduous trees decreased. Compared with the deciduous trees, the evergreen trees were more sensitive to the feedback of soil N and P concentrations. These findings reveal the N and P nutrient resorption mechanism of evergreen and deciduous trees and fill a gap in the understanding of nutrient resorption in urban ecosystems.


Asunto(s)
Ecosistema , Árboles , Árboles/fisiología , Jardines , Suelo , Fósforo , Hojas de la Planta/fisiología , Nitrógeno , Nutrientes
15.
Plant Signal Behav ; 18(1): 2215025, 2023 12 31.
Artículo en Inglés | MEDLINE | ID: mdl-37243677

RESUMEN

Yellow horn grows in northern China and has a high tolerance to drought and poor soil. Improving photosynthetic efficiency and increasing plant growth and yield under drought conditions have become important research content for researchers worldwide. Our study goal is to provide comprehensive information on photosynthesis and some candidate genes breeding of yellow horn under drought stress. In this study, seedlings' stomatal conductance, chlorophyll content, and fluorescence parameters decreased under drought stress, but non-photochemical quenching increased. The leaf microstructure showed that stomata underwent a process from opening to closing, guard cells from complete to dry, and surrounding leaf cells from smooth to severe shrinkage. The chloroplast ultrastructure showed that the changes of starch granules were different under different drought stress, while plastoglobules increased and expanded continuously. In addition, we found some differentially expressed genes related to photosystem, electron transport component, oxidative phosphate ATPase, stomatal closure, and chloroplast ultrastructure. These results laid a foundation for further genetic improvement and deficit resistance breeding of yellow horn under drought stress.


Asunto(s)
Sequías , Fotosíntesis , Fotosíntesis/genética , Clorofila/metabolismo , Hojas de la Planta/genética , Hojas de la Planta/metabolismo , Expresión Génica , Agua/metabolismo , Estrés Fisiológico/genética
16.
Cell Oncol (Dordr) ; 46(4): 1143-1157, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37219767

RESUMEN

PURPOSE: Chimeric antigen receptor (CAR)-T cells against CD19 have been proven to be effective in treating B-cell hematological malignancies. However, the efficacy of this promising therapy is limited by many factors. METHODS: In this study, the germinal center B-cell-like diffuse large B-cell lymphoma (GCB-DLBCL) cell line OCI-Ly1, and patient-derived xenografted (PDX) mice (CY-DLBCL) were used as the CAR-T cell-resistant model. Meanwhile, the activated B-cell-like (ABC) DLBCL cell line OCI-Ly3 and PDX mice (ZML-DLBCL) were defined as the CAR-T sensitive model. The enhancement of CAR-T cell function by lenalidomide (LEN) was examined in vitro and in vivo. RESULTS: Lenalidomide effectively enhanced the function of third-generation CD19-CAR-T cells by polarizing CD8+ CAR-T cells to CD8 early-differentiated stage and Th1 type, reducing CAR-T cell exhaustion and improving cell expansion. It was further demonstrated that CAR-T cells combined with LEN substantially reduce the tumor burden and prolong the survival time in various DLBCL mouse models. LEN was also found to promote the infiltration of CD19-CAR-T cells into the tumor site by modulating the tumor microenvironment. CONCLUSION: In summary, the results of the present study suggest that LEN can improve the function of CD19-CAR-T cells, providing a basis for clinical trials using this combination therapy against DLBCL.


Asunto(s)
Linfoma de Células B Grandes Difuso , Receptores Quiméricos de Antígenos , Animales , Ratones , Proteínas Adaptadoras Transductoras de Señales , Antígenos CD19/inmunología , Tratamiento Basado en Trasplante de Células y Tejidos , Inmunoterapia Adoptiva/métodos , Lenalidomida/farmacología , Lenalidomida/uso terapéutico , Linfoma de Células B Grandes Difuso/terapia , Linfoma de Células B Grandes Difuso/patología , Receptores Quiméricos de Antígenos/inmunología , Microambiente Tumoral , Humanos
17.
Front Immunol ; 14: 1149513, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37138885

RESUMEN

Acute myeloid leukemia (AML) is a highly aggressive cancer with great heterogeneity and variability in prognosis. Though European Leukemia Net (ELN) 2017 risk classification has been widely used, nearly half of patients were stratified to "intermediate" risk and requires more accurate classification via excavating biological features. As new evidence showed that CD8+ T cell can kill cancer cells through ferroptosis pathway. We firstly use CIBERSORT algorithm to divide AMLs into CD8+ high and CD8+ low T cell groups, then 2789 differentially expressed genes (DEGs) between groups were identified, of which 46 ferroptosis-related genes associated with CD8+ T cell were sorted out. GO, KEGG analysis and PPI network were conducted based on these 46 DEGs. By jointly using LASSO algorithm and Cox univariate regression, we generated a 6-gene prognostic signature comprising VEGFA, KLHL24, ATG3, EIF2AK4, IDH1 and HSPB1. Low-risk group shows a longer overall survival. We then validated the prognostic value of this 6-gene signature using two independent external datasets and patient sample collection dataset. We also proved that incorporation of the 6-gene signature obviously enhanced the accuracy of ELN risk classification. Finally, gene mutation analysis, drug sensitive prediction, GSEA and GSVA analysis were conducted between high-risk and low-risk AML patients. Collectively, our findings suggested that the prognostic signature based on CD8+ T cell-related ferroptosis genes can optimize the risk stratification and prognostic prediction of AML patients.


Asunto(s)
Ferroptosis , Leucemia Mieloide Aguda , Humanos , Ferroptosis/genética , Pronóstico , Leucemia Mieloide Aguda/genética , Linfocitos T CD8-positivos , Algoritmos , Proteínas Serina-Treonina Quinasas
18.
Plants (Basel) ; 12(9)2023 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-37176916

RESUMEN

Legume medicinal plants Astragalus membranaceus are widely used in the world and have very important economic value, ecological value, medicinal value, and ornamental value. The bioengineering technology of medicinal plants is used in the protection of endangered species, the rapid propagation of important resources, detoxification, and the improvement of degraded germplasm. Using bioengineering technology can effectively increase the content of secondary metabolites in A. membranaceus and improve the probability of solving the problem of medicinal plant resource shortage. In this review, we focused on biotechnological research into A. membranaceus, such as the latest advances in tissue culture, including callus, adventitious roots, hairy roots, suspension cells, etc., the metabolic regulation of chemical compounds in A. membranaceus, and the research progress on the synthetic biology of astragalosides, including the biosynthesis pathway of astragalosides, microbial transformation of astragalosides, and metabolic engineering of astragalosides. The review also looks forward to the new development trend of medicinal plant biotechnology, hoping to provide a broader development prospect for the in-depth study of medicinal plants.

19.
Nano Lett ; 23(11): 5209-5216, 2023 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-37227052

RESUMEN

Upconversion nanoparticles (UCNPs) doped with lanthanides have limited brightness due to their small absorption cross section to light. However, using organic sensitizers can significantly enhance their light absorption ability. Unfortunately, the practical application of organic sensitizers has been hindered by poor stability and aggregation-caused quenching (ACQ). To address these issues, we developed a novel squaraine-based dye, SQ-739, for sensitizing upconversion luminescence (UCL). This dye has a maximum absorption at 739 nm, and shows 1 order of magnitude and 2-fold improved chemical- and photostability, compared to the commonly used cyanine-based dye IR-806, respectively. When SQ-739 is used to sensitize UCNPs, the resulting SQ-739-UCNPs exhibit excellent photostability and reduced ACQ in the presence of polar solvents. Moreover, at the single particle level, the SQ-739-UCNPs exhibit a 97-fold increase in UCL emission compared to bare UCNPs. This squaraine dye-based system represents a new design strategy for developing highly stable and efficient NIR upconversion probes.

20.
Plants (Basel) ; 12(7)2023 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-37050131

RESUMEN

At present, most precious compounds are still obtained by plant cultivation such as ginsenosides, glycyrrhizic acid, and paclitaxel, which cannot be easily obtained by artificial synthesis. Plant tissue culture technology is the most commonly used biotechnology tool, which can be used for a variety of studies such as the production of natural compounds, functional gene research, plant micropropagation, plant breeding, and crop improvement. Tissue culture material is a basic and important part of this issue. The formation of different plant tissues and natural products is affected by growth conditions and endogenous substances. The accumulation of secondary metabolites are affected by plant tissue type, culture method, and environmental stress. Multi-domain technologies are developing rapidly, and they have made outstanding contributions to the application of plant tissue culture. The modes of action have their own characteristics, covering the whole process of plant tissue from the induction, culture, and production of natural secondary metabolites. This paper reviews the induction mechanism of different plant tissues and the application of multi-domain technologies such as artificial intelligence, biosensors, bioreactors, multi-omics monitoring, and nanomaterials in plant tissue culture and the production of secondary metabolites. This will help to improve the tissue culture technology of medicinal plants and increase the availability and the yield of natural metabolites.

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