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1.
J Med Chem ; 67(8): 6822-6838, 2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38588468

RESUMEN

Weak antigens represented by MUC1 are poorly immunogenic, which greatly constrains the development of relevant vaccines. Herein, we developed a multifunctional lipidated protein as a carrier, in which the TLR1/2 agonist Pam3CSK4 was conjugated to the N-terminus of MUC1-loaded carrier protein BSA through pyridoxal 5'-phosphate-mediated transamination reaction. The resulting Pam3CSK4-BSA-MUC1 conjugate was subsequently incorporated into liposomes, which biomimics the membrane structure of tumor cells. The results indicated that this lipidated protein carrier significantly enhanced antigen uptake by APCs and obviously augmented the retention of the vaccine at the injection site. Compared with the BSA-MUC1 and BSA-MUC1 + Pam3CSK4 groups, Pam3CSK4-BSA-MUC1 evoked 22- and 11-fold increases in MUC1-specific IgG titers. Importantly, Pam3CSK4-BSA-MUC1 elicited robust cellular immunity and significantly inhibited tumor growth. This is the first time that lipidated protein was constructed to enhance antigen immunogenicity, and this universal carrier platform exhibits promise for utilization in various vaccines, holding the potential for further clinical application.


Asunto(s)
Liposomas , Mucina-1 , Animales , Mucina-1/inmunología , Mucina-1/química , Ratones , Humanos , Lipopéptidos/química , Lipopéptidos/inmunología , Lipopéptidos/farmacología , Vacunas contra el Cáncer/inmunología , Vacunas contra el Cáncer/química , Albúmina Sérica Bovina/química , Adyuvantes Inmunológicos/farmacología , Adyuvantes Inmunológicos/química , Femenino , Ratones Endogámicos BALB C , Antígenos/inmunología , Línea Celular Tumoral
2.
BMC Cancer ; 24(1): 441, 2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38594604

RESUMEN

BACKGROUND: We recently found that epiplakin 1 (EPPK1) alterations were present in 12% of lung adenocarcinoma (LUAD) cases and were associated with a poor prognosis in early-stage LUAD when combined with other molecular alterations. This study aimed to identify a probable crucial role for EPPK1 in cancer development. METHODS: EPPK1 mRNA and protein expression was analyzed with clinical variables. Normal bronchial epithelial cell lines were exposed to cigarette smoke for 16 weeks to determine whether EPPK1 protein expression was altered after exposure. Further, we used CRISPR-Cas9 to knock out (KO) EPPK1 in LUAD cell lines and observed how the cancer cells were altered functionally and genetically. RESULTS: EPPK1 protein expression was associated with smoking and poor prognosis in early-stage LUAD. Moreover, a consequential mesenchymal-to-epithelial transition was observed, subsequently resulting in diminished cell proliferation and invasion after EPPK1 KO. RNA sequencing revealed that EPPK1 KO induced downregulation of 11 oncogenes, 75 anti-apoptosis, and 22 angiogenesis genes while upregulating 8 tumor suppressors and 12 anti-cell growth genes. We also observed the downregulation of MYC and upregulation of p53 expression at both protein and RNA levels following EPPK1 KO. Gene ontology enrichment analysis of molecular functions highlighted the correlation of EPPK1 with the regulation of mesenchymal cell proliferation, mesenchymal differentiation, angiogenesis, and cell growth after EPPK1 KO. CONCLUSIONS: Our data suggest that EPPK1 is linked to smoking, epithelial to mesenchymal transition, and the regulation of cancer progression, indicating its potential as a therapeutic target for LUAD.


Asunto(s)
Adenocarcinoma del Pulmón , Adenocarcinoma , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/patología , Transición Epitelial-Mesenquimal/genética , Pronóstico , Adenocarcinoma del Pulmón/patología , Adenocarcinoma/patología , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Línea Celular Tumoral
3.
Org Lett ; 26(11): 2212-2217, 2024 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-38452132

RESUMEN

In this report, we present a photopromoted, metal-free transannulation of phenyl azides for the synthesis of DNA-encoded seven-membered rings. The transformation is efficiently achieved through a skeletal editing strategy targeting the benzene motif coupled with a Reversible Adsorption to Solid Support (RASS) strategy. A variety of valuable DNA-encoded seven-membered ring compounds, including DNA-encoded 3H-azepines, azepinones, and unnatural amino acids, are now accessible. Crucially, this DNA-compatible protocol can also be applied for the introduction of complex molecules, as exemplified by Lorcaserin and Betahistine. The selective conversion of readily available phenyl rings into high-value seven-membered rings offers a promising avenue for the construction of diversified and drug-like DNA-encoded library.


Asunto(s)
Azidas , Benceno , Ciclización , Aminas , ADN
4.
Front Public Health ; 12: 1295924, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38327571

RESUMEN

Purpose: Recent studies have shown that physical activity (PA) levels are low among children and adolescents globally. In order to reverse this trend, PA interventions are increasingly favoured. The school setting is the ideal place to address the issues that many children face. The purpose of this study was to (a) The primary focus of this study is to delve into the mediating role played by school-based rope skipping sports participation (SRSP) in the connection between social support and moderate to high-intensity physical activity (MVPA) among school children. (b) Additionally, this research aims to examine the moderating effect of within this pathway. Methods: We conducted a survey involving 721 adolescents residing in Changsha City. The participants' ages ranged from 8 to 12 years, with an average age of 9.84 ± 1.535 years. Out of these participants, 406 were boys, and 315 were girls. To assess variables such as social support and autonomous motivation, we employed standardized measurement scales. Subsequently, we analyzed the collected data using various statistical methods, including independent s-amples t-tests, bivariate correlation analysis, descriptive statistical analysis, structural equation modeling (SEM), and the Johnson-Neyman method. Results: An independent samples t-test revealed a statistically significant difference in MVPA between genders (p = 0.003 < 0.05), with boys exhibiting a higher level of engagement in MVPA compared to girls, Correlation analysis revealed significant positive associations among several key variables. Specifically, social support demonstrated a noteworthy positive correlation with autonomous motivation (r = 0.331, p < 0.01) as well as school children's engagement in MVPA (r = 0.308, p < 0.01). Moreover, autonomous motivation displayed a significant positive correlation with school children's involvement in MVPA (r = 0.459, p < 0.01). The moderating analysis revealed a significant influence of the interaction between increased participation in and social support on school children's engagement in MVPA. Conclusion: Social support and autonomy support have been proven effective in enhancing school children's engagement in MVPA. They exert their influence indirectly by fostering autonomous motivation. Notably, robust social support can significantly benefit MVPA school children with high activity requirements, particularly those regularly engaged in MVPA during the school day.


Asunto(s)
Motivación , Deportes , Niño , Adolescente , Humanos , Masculino , Femenino , Conducta Infantil , Ejercicio Físico , Apoyo Social
5.
J Org Chem ; 89(4): 2726-2740, 2024 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-38307838

RESUMEN

A facile and efficient approach for the synthesis of multisubstituted tetrahydropyridazines starting from cyclopropyl ketones and hydrazines has been developed. The transformation is chalcone-based and takes place via a Cloke-Wilson-type rearrangement-involved tandem reaction catalyzed by TfOH in HFIP.

6.
Environ Res ; 249: 118236, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38266893

RESUMEN

Excessive noise exposure presents significant health risks to humans, affecting not just the auditory system but also the cardiovascular and central nervous systems. This study focused on three male macaque monkeys as subjects. 90 dB sound pressure level (SPL) pure tone exposure (frequency: 500Hz, repetition rate: 40Hz, 1 min per day, continuously exposed for 5 days) was administered. Assessments were performed before exposure, during exposure, immediately after exposure, and at 7-, 14-, and 28-days post-exposure, employing auditory brainstem response (ABR) tests, electrocardiograms (ECG), and electroencephalograms (EEG). The study found that the average threshold for the Ⅴ wave in the right ear increased by around 30 dB SPL right after exposure (P < 0.01) compared to pre-exposure. This elevation returned to normal within 7 days. The ECG results indicated that one of the macaque monkeys exhibited an RS-type QRS wave, and inverted T waves from immediately after exposure to 14 days, which normalized at 28 days. The other two monkeys showed no significant changes in their ECG parameters. Changes in EEG parameters demonstrated that main brain regions exhibited significant activation at 40Hz during noise exposure. After noise exposure, the power spectral density (PSD) in main brain regions, particularly those represented by the temporal lobe, exhibited a decreasing trend across all frequency bands, with no clear recovery over time. In summary, exposure to 90 dB SPL noise results in impaired auditory systems, aberrant brain functionality, and abnormal electrocardiographic indicators, albeit with individual variations. It has implications for establishing noise protection standards, although the precise mechanisms require further exploration by integrating pathological and behavioral indicators.


Asunto(s)
Electrocardiografía , Electroencefalografía , Potenciales Evocados Auditivos del Tronco Encefálico , Ruido , Animales , Masculino , Ruido/efectos adversos , Macaca/fisiología
7.
Huan Jing Ke Xue ; 45(1): 470-479, 2024 Jan 08.
Artículo en Chino | MEDLINE | ID: mdl-38216496

RESUMEN

Contaminants such as microplastics (MPs) and heavy metals are commonly found in soils, both of which are extremely difficult to degrade and can easily form compound contamination, altering the physicochemical properties of the soil and thus potentially changing the growth and physiological and ecological characteristics of plants. In order to study the effects of the combined contamination of soil MPs and heavy metals on soil properties and plant growth, polystyrene microplastics (PS-MPs) with a particle size of 3 µm and the heavy metal cadmium were selected in the study. The changes in the physicochemical properties of soil and their effects on lettuce (Lactuca sativa) seed germination and seedling growth were studied at various exposure concentrations of PS-MPs (0, 10, 50, 100, 200, and 400 mg·kg-1) and combined with different Cd contamination concentrations (0, 1.2, and 6.0 mg·kg-1), respectively. The results showed that soil organic matter (SOM), available phosphorus (AP), alkali-hydrolysable nitrogen (AHN), and available kalium (AK) showed significant decreases as the intensity of PS-MPs combined with Cd contamination increased. Simultaneously, PS-MPs combined with Cd contamination also significantly reduced the germination rate of lettuce seeds, but low concentrations of PS-MPs slowed down the effect of Cd (6.0 mg·kg-1) contamination on lettuce seeds, and high concentrations of PS-MPs enhanced the effect of Cd (6.0 mg·kg-1). The fresh weight, dry weight, and plant height of lettuce seedlings showed an increasing and then decreasing trend with increasing exposure to PS-MPs. Chlorophyll content, superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD) showed a decreasing trend, whereas malondialdehyde (MDA) content showed an overall increasing trend under different Cd concentrations. The main physicochemical indicators of the soil were negatively correlated with MDA of lettuce seedlings, whereas other indicators of the seedlings were positively correlated. The combined contamination of PS-MPs and Cd could affect the germination of plant seeds and the physiological and ecological characteristics of seedlings by changing the physicochemical properties of the soil. Both exposure to single PS-MPs contaminants and the combination of PS-MPs with Cd inhibited the germination of lettuce seeds and affected the physiological activities of their seedlings, and the inhibition was significantly increased with increasing exposure. Low exposure to PS-MPs or the combination of PS-MPs with Cd contamination exhibited a promotive effect on lettuce seedling growth. High exposure to PS-MPs combined with Cd contamination exhibited significant ecological effects on lettuce seedlings, and high exposure to PS-MPs exacerbated the ecotoxicological effects of Cd contaminants on lettuce seedlings, and PS-MPs and Cd exhibited synergistic effects. The results can provide some reference for assessing the ecological effects of MPs and heavy metal pollution in soil-plant systems.


Asunto(s)
Metales Pesados , Contaminantes del Suelo , Cadmio/toxicidad , Cadmio/metabolismo , Microplásticos , Lactuca , Plásticos , Poliestirenos , Suelo , Metales Pesados/metabolismo , Plantones , Contaminantes del Suelo/análisis
8.
Cell Biosci ; 14(1): 2, 2024 Jan 04.
Artículo en Inglés | MEDLINE | ID: mdl-38178181

RESUMEN

BACKGROUND: Attention provides the foundation for cognitions, which was shown to be affected by microwave (MW) radiation. With the ubiquitous of microwaves, public concerns regarding the impact of MW radiation on attention has hence been increased. Our study aims to investigate the potential effect and mechanism of acute microwave exposure on attention. RESULTS: We identified obvious impairment of attention in mice by the five-choice serial reaction time (5-CSRT) task. Proteomic analysis of the cerebrospinal fluid (CSF) revealed neuroinflammation and microglial activation potentially due to acute MW exposure. Moreover, biochemical analysis further confirmed microglial activation in the prefrontal cortex (PFC) of mice subjected to acute MW exposure. Finally, minocycline, a commercially available anti-inflammatory compound, attenuated neuroinflammation, inhibited the upregulation of N-methyl-D-aspartic acid receptor (NMDAR) including NR2A and NR2B, and also accelerated the attentional recovery after MW exposure. CONCLUSIONS: We believe that microglial activation and NMDAR upregulation likely contribute to inattention induced by acute MW exposure, and we found that minocycline may be effective in preventing such process.

9.
Oncol Rep ; 51(3)2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38240098

RESUMEN

Following the publication of the above article, a concerned reader drew to the Editor's attention that the Transwell cell invasion assay data featured in Figs. 3 and 5, and the cell microscopic/morphological images shown in Fig. 4A and C, were strikingly similar to data appearing in different form in other articles written by different authors at different research institutes that had either already been published elsewhere prior to the submission of this paper to Oncology Reports, or which under consideration for publication at around the same time (several of which have now been retracted). In addition, overlapping sections of data were noted within Figs. 3 and 5, such that data which were intended to represent the results from differently performed experiments had apparently been derived from the same original source(s). In view of the fact that certain of these data had already apparently been published prior to the submission of this article for publication, the Editor of Oncology Reports has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they agreed with the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 36: 3105­3112, 2016; DOI: 10.3892/or.2016.5146].

10.
Plant Cell ; 36(3): 665-687, 2024 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-37971931

RESUMEN

Caspases are restricted to animals, while other organisms, including plants, possess metacaspases (MCAs), a more ancient and broader class of structurally related yet biochemically distinct proteases. Our current understanding of plant MCAs is derived from studies in streptophytes, and mostly in Arabidopsis (Arabidopsis thaliana) with 9 MCAs with partially redundant activities. In contrast to streptophytes, most chlorophytes contain only 1 or 2 uncharacterized MCAs, providing an excellent platform for MCA research. Here we investigated CrMCA-II, the single type-II MCA from the model chlorophyte Chlamydomonas (Chlamydomonas reinhardtii). Surprisingly, unlike other studied MCAs and similar to caspases, CrMCA-II dimerizes both in vitro and in vivo. Furthermore, activation of CrMCA-II in vivo correlated with its dimerization. Most of CrMCA-II in the cell was present as a proenzyme (zymogen) attached to the plasma membrane (PM). Deletion of CrMCA-II by genome editing compromised thermotolerance, leading to increased cell death under heat stress. Adding back either wild-type or catalytically dead CrMCA-II restored thermoprotection, suggesting that its proteolytic activity is dispensable for this effect. Finally, we connected the non-proteolytic role of CrMCA-II in thermotolerance to the ability to modulate PM fluidity. Our study reveals an ancient, MCA-dependent thermotolerance mechanism retained by Chlamydomonas and probably lost during the evolution of multicellularity.


Asunto(s)
Arabidopsis , Chlorophyta , Animales , Plantas/metabolismo , Caspasas/genética , Caspasas/química , Caspasas/metabolismo , Arabidopsis/genética , Membrana Celular/metabolismo
11.
Commun Biol ; 6(1): 1126, 2023 11 07.
Artículo en Inglés | MEDLINE | ID: mdl-37935873

RESUMEN

N-acetylserotonin O-methyltransferase (ASMT) is responsible for melatonin biosynthesis. The Asmt gene is located on the X chromosome, and its genetic polymorphism is associated with depression in humans. However, the underlying mechanism remains unclear. Here, we use CRISPR/Cas9 to delete 20 bp of exon 2 of Asmt, and construct C57BL/6J mouse strain with Asmt frameshift mutation (Asmtft/ft). We show that female Asmtft/ft mice exhibit anxiety- and depression-like behaviors, accompanied by an obvious structural remodeling of gut microbiota. These behavioral abnormalities are not observed in male. Moreover, female Asmtft/ft mice show a lower neurobehavioral adaptability to exercise, while wild-type shows a "higher resilience". Cross-sectional and longitudinal analysis indicates that the structure of gut microbiota in Asmtft/ft mice is less affected by exercise. These results suggests that Asmt maintains the plasticity of gut microbiota in female, thereby enhancing the neurobehavioral adaptability to exercise.


Asunto(s)
Microbioma Gastrointestinal , Melatonina , Humanos , Animales , Masculino , Femenino , Ratones , Acetilserotonina O-Metiltransferasa/química , Acetilserotonina O-Metiltransferasa/genética , Estudios Transversales , Ratones Endogámicos C57BL
12.
Sci Rep ; 13(1): 17604, 2023 10 17.
Artículo en Inglés | MEDLINE | ID: mdl-37848457

RESUMEN

Lung adenocarcinoma (LUAD) is the predominant type of lung cancer in the U.S. and exhibits a broad variety of behaviors ranging from indolent to aggressive. Identification of the biological determinants of LUAD behavior at early stages can improve existing diagnostic and treatment strategies. Extracellular matrix (ECM) remodeling and cancer-associated fibroblasts play a crucial role in the regulation of cancer aggressiveness and there is a growing need to investigate their role in the determination of LUAD behavior at early stages. We analyzed tissue samples isolated from patients with LUAD at early stages and used imaging-based biomarkers to predict LUAD behavior. Single-cell RNA sequencing and histological assessment showed that aggressive LUADs are characterized by a decreased number of ADH1B+ CAFs in comparison to indolent tumors. ADH1B+ CAF enrichment is associated with distinct ECM and immune cell signatures in early-stage LUADs. Also, we found a positive correlation between the gene expression of ADH1B+ CAF markers in early-stage LUADs and better survival. We performed TCGA dataset analysis to validate our findings. Identified associations can be used for the development of the predictive model of LUAD aggressiveness and novel therapeutic approaches.


Asunto(s)
Adenocarcinoma del Pulmón , Fibroblastos Asociados al Cáncer , Síndrome de DiGeorge , Neoplasias Pulmonares , Humanos , Adenocarcinoma del Pulmón/genética , Agresión , Neoplasias Pulmonares/genética , Pronóstico , Biomarcadores de Tumor/genética
13.
J Exp Med ; 220(12)2023 12 04.
Artículo en Inglés | MEDLINE | ID: mdl-37851372

RESUMEN

Infection is able to promote innate immunity by enhancing a long-term myeloid output even after the inciting infectious agent has been cleared. However, the mechanisms underlying such a regulation are not fully understood. Using a mouse polymicrobial peritonitis (sepsis) model, we show that severe infection leads to increased, sustained myelopoiesis after the infection is resolved. In post-infection mice, the tissue inhibitor of metalloproteinases 1 (TIMP1) is constitutively upregulated. TIMP1 antagonizes the function of ADAM10, an essential cleavage enzyme for the activation of the Notch signaling pathway, which suppresses myelopoiesis. While TIMP1 is dispensable for myelopoiesis under the steady state, increased TIMP1 enhances myelopoiesis after infection. Thus, our data establish TIMP1 as a molecular reporter of past infection in the host, sustaining hyper myelopoiesis and serving as a potential therapeutic target for modulating HSPC cell fate.


Asunto(s)
Hematopoyesis , Sepsis , Animales , Ratones , Diferenciación Celular , Inmunidad Innata , Mielopoyesis , Inhibidor Tisular de Metaloproteinasa-1/genética
14.
Front Optoelectron ; 16(1): 31, 2023 Oct 31.
Artículo en Inglés | MEDLINE | ID: mdl-37906336

RESUMEN

Optical thermometry based on the upconversion (UC) luminescence intensity ratio (LIR) has attracted considerable attention because of its feasibility for achievement of accurate non-contact temperature measurement. Compared with traditional UC phosphors, optical thermometry based on UC single crystals can achieve faster response and higher sensitivity due to the stability and high thermal conductivity of the single crystals. In this study, a high-quality 5 at% Yb3+ and 1 at% Ho3+ co-doped Gd0.74Y0.2TaO4 single crystal was grown by the Czochralski (Cz) method, and the structure of the as-grown crystal was characterized. Importantly, the UC luminescent properties and optical thermometry behaviors of this crystal were revealed. Under 980 nm wavelength excitation, green and red UC luminescence lines at 550 and 650 nm and corresponding to the 5F4/5S2 → 5I8 and 5F5 → 5I8 transitions of Ho3+, respectively, were observed. The green and red UC emissions involved a two-photon mechanism, as evidenced by the analysis of power-dependent UC emission spectra. The temperature-dependent UC emission spectra were measured in the temperature range of 330-660 K to assess the optical temperature sensing behavior. At 660 K, the maximum relative sensing sensitivity (Sr) was determined to be 0.0037 K-1. These results highlight the significant potential of Yb,Ho:GYTO single crystal for optical temperature sensors.

15.
J Vis Exp ; (200)2023 10 13.
Artículo en Inglés | MEDLINE | ID: mdl-37902316

RESUMEN

Circulating tumor cells (CTCs) are significant in cancer prognosis, diagnosis, and anti-cancer therapy. CTC enumeration is vital in determining patient disease since CTCs are rare and heterogeneous. CTCs are detached from the primary tumor, enter the blood circulation system, and potentially grow at distant sites, thus metastasizing the tumor. Since CTCs carry similar information to the primary tumor, CTC isolation and subsequent characterization can be critical in monitoring and diagnosing cancer. The enumeration, affinity modification, and clinical immunofluorescence staining of rare CTCs are powerful methods for CTC isolation because they provide the necessary elements with high sensitivity. Microfluidic chips offer a liquid biopsy method that is free of any pain for the patients. In this work, we present a list of protocols for clinical microfluidic chips, a versatile CTC isolating platform, that incorporate a set of functionalities and services required for CTC separation, analysis, and early diagnosis, thus facilitating biomolecular analysis and cancer treatment. The program includes rare tumor cell counting, clinical patient blood preprocessing, which includes red blood cell lysis, and the isolation and recognition of CTCs in situ on microfluidic chips. The program allows the precise enumeration of tumor cells or CTCs. Additionally, the program includes a tool that incorporates CTC isolation with versatile microfluidic chips and immunofluorescence identification in situ on the chips, followed by biomolecular analysis.


Asunto(s)
Técnicas Analíticas Microfluídicas , Células Neoplásicas Circulantes , Humanos , Células Neoplásicas Circulantes/patología , Microfluídica/métodos , Separación Celular/métodos , Recuento de Células , Línea Celular Tumoral , Técnicas Analíticas Microfluídicas/métodos
16.
Proc Natl Acad Sci U S A ; 120(43): e2308658120, 2023 Oct 24.
Artículo en Inglés | MEDLINE | ID: mdl-37844234

RESUMEN

Dysregulated apoptosis and proliferation are fundamental properties of cancer, and microRNAs (miRNA) are critical regulators of these processes. Loss of miR-15a/16-1 at chromosome 13q14 is the most common genomic aberration in chronic lymphocytic leukemia (CLL). Correspondingly, the deletion of either murine miR-15a/16-1 or miR-15b/16-2 locus in mice is linked to B cell lymphoproliferative malignancies. However, unexpectedly, when both miR-15/16 clusters are eliminated, most double knockout (DKO) mice develop acute myeloid leukemia (AML). Moreover, in patients with CLL, significantly reduced expression of miR-15a, miR-15b, and miR-16 associates with progression of myelodysplastic syndrome to AML, as well as blast crisis in chronic myeloid leukemia. Thus, the miR-15/16 clusters have a biological relevance for myeloid neoplasms. Here, we demonstrate that the myeloproliferative phenotype in DKO mice correlates with an increase of hematopoietic stem and progenitor cells (HSPC) early in life. Using single-cell transcriptomic analyses, we presented the molecular underpinning of increased myeloid output in the HSPC of DKO mice with gene signatures suggestive of dysregulated hematopoiesis, metabolic activities, and cell cycle stages. Functionally, we found that multipotent progenitors (MPP) of DKO mice have increased self-renewing capacities and give rise to significantly more progeny in the granulocytic compartment. Moreover, a unique transcriptomic signature of DKO MPP correlates with poor outcome in patients with AML. Together, these data point to a unique regulatory role for miR-15/16 during the early stages of hematopoiesis and to a potentially useful biomarker for the pathogenesis of myeloid neoplasms.


Asunto(s)
Leucemia Linfocítica Crónica de Células B , Leucemia Mieloide Aguda , MicroARNs , Trastornos Mieloproliferativos , Humanos , Animales , Ratones , Leucemia Linfocítica Crónica de Células B/genética , MicroARNs/metabolismo , Células Madre Hematopoyéticas/metabolismo , Leucemia Mieloide Aguda/metabolismo , División Celular , Trastornos Mieloproliferativos/genética
17.
J Trop Pediatr ; 69(5)2023 09 07.
Artículo en Inglés | MEDLINE | ID: mdl-37674390

RESUMEN

Coronavirus disease 2019 (COVID-19) has become a significant global public health problem. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which causes the disease, utilizes angiotensin-converting enzyme II (ACE2) as a major functional receptor to enter host cells. No study has systematically assessed ACE2 expression in multiple tissues in children. This study investigated ACE2 expression and ACE2 protein's histological distribution in various organs in paediatric patients (the small intestine, thymus, heart and lungs). Our study revealed that ACE2 was highly expressed in enterocytes of the small intestine and widely expressed in the myocardium of heart tissues. The most notable finding was the positive staining of ACE2 in the Hassall's corpuscles epithelial cells. Negligible ACE2 expression in the lung tissues may contribute to a lower risk of infection and fewer symptoms of pneumonia in children than in adults with COVID-19 infection. These findings provide initial evidence for understanding SARS-CoV-2 pathogenesis and prevention strategies in paediatric clinical practice, which should be applicable for all children worldwide.


Asunto(s)
COVID-19 , SARS-CoV-2 , Adulto , Humanos , Niño , Enzima Convertidora de Angiotensina 2/genética , Corazón , Salud Pública
18.
JTO Clin Res Rep ; 4(9): 100504, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37674811

RESUMEN

Introduction: Lung cancer is the deadliest cancer in the United States and worldwide, and lung adenocarcinoma (LUAD) is the most prevalent histologic subtype in the United States. LUAD exhibits a wide range of aggressiveness and risk of recurrence, but the biological underpinnings of this behavior are poorly understood. Past studies have focused on the biological characteristics of the tumor itself, but the ability of the immune response to contain tumor growth represents an alternative or complementary hypothesis. Emerging technologies enable us to investigate the spatial distribution of specific cell types within the tumor nest and characterize this immune response. This study aimed to investigate the association between immune cell density within the primary tumor and recurrence-free survival (RFS) in stage I and II LUAD. Methods: This study is a prospective collection with retrospective evaluation. A total of 100 patients with surgically resected LUAD and at least 5-year follow-ups, including 69 stage I and 31 stages II tumors, were enrolled. Multiplexed immunohistochemistry panels for immune markers were used for measurement. Results: Cox regression models adjusted for sex and EGFR mutation status revealed that the risk of recurrence was reduced by 50% for the unit of one interquartile range (IQR) change in the tumoral T-cell (adjusted hazard ratio per IQR increase = 0.50, 95% confidence interval: 0.27-0.93) and decreased by 64% in mast cell density (adjusted hazard ratio per IQR increase = 0.36, confidence interval: 0.15-0.84). The analyses were reported without the type I error correction for the multiple types of immune cell testing. Conclusions: Analysis of the density of immune cells within the tumor and surrounding stroma reveals an association between the density of T-cells and RFS and between mast cells and RFS in early-stage LUAD. This preliminary result is a limited study with a small sample size and a lack of an independent validation set.

20.
Chem Commun (Camb) ; 59(79): 11855-11858, 2023 Oct 04.
Artículo en Inglés | MEDLINE | ID: mdl-37721202

RESUMEN

The frustrated Lewis pair (FLP) site of (Ce, Ce)-O on the CeO2(110) surface undergoes reconstruction to form (La, Ce)-O upon La-doping. The FLP site of (La, Ce)-O with the tailored local Lewis acid-base property and increased spatial distance between the Lewis acid and base facilitates the tandem transformation of styrene and CO2 through the weakened adsorption of CO2 while maintaining activation.

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