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1.
Proc Natl Acad Sci U S A ; 121(15): e2313921121, 2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38568968

RESUMEN

Malvaceae comprise some 4,225 species in 243 genera and nine subfamilies and include economically important species, such as cacao, cotton, durian, and jute, with cotton an important model system for studying the domestication of polyploids. Here, we use chromosome-level genome assemblies from representatives of five or six subfamilies (depending on the placement of Ochroma) to differentiate coexisting subgenomes and their evolution during the family's deep history. The results reveal that the allohexaploid Helicteroideae partially derive from an allotetraploid Sterculioideae and also form a component of the allodecaploid Bombacoideae and Malvoideae. The ancestral Malvaceae karyotype consists of 11 protochromosomes. Four subfamilies share a unique reciprocal chromosome translocation, and two other subfamilies share a chromosome fusion. DNA alignments of single-copy nuclear genes do not yield the same relationships as inferred from chromosome structural traits, probably because of genes originating from different ancestral subgenomes. These results illustrate how chromosome-structural data can unravel the evolutionary history of groups with ancient hybrid genomes.


Asunto(s)
Genoma de Planta , Gossypium , Genoma de Planta/genética , Gossypium/genética , Genómica/métodos , Poliploidía , Cariotipo , Evolución Molecular
2.
Nucleic Acids Res ; 52(5): 2463-2479, 2024 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-38281188

RESUMEN

Ribosomal frameshifting refers to the process that ribosomes slip into +1 or -1 reading frame, thus produce chimeric trans-frame proteins. In viruses and bacteria, programmed ribosomal frameshifting can produce essential trans-frame proteins for viral replication or regulation of other biological processes. In humans, however, functional trans-frame protein derived from ribosomal frameshifting is scarcely documented. Combining multiple assays, we show that short codon repeats could act as cis-acting elements that stimulate ribosomal frameshifting in humans, abbreviated as CRFS hereafter. Using proteomic analyses, we identified many putative CRFS events from 32 normal human tissues supported by trans-frame peptides positioned at codon repeats. Finally, we show a CRFS-derived trans-frame protein (HDAC1-FS) functions by antagonizing the activities of HDAC1, thus affecting cell migration and apoptosis. These data suggest a novel type of translational recoding associated with codon repeats, which may expand the coding capacity of mRNA and diversify the regulation in human.


Asunto(s)
Sistema de Lectura Ribosómico , Proteómica , Humanos , Codón/genética , Codón/metabolismo , Ribosomas/metabolismo , Proteínas Recombinantes de Fusión/metabolismo , Biosíntesis de Proteínas
3.
Proc Natl Acad Sci U S A ; 120(45): e2304848120, 2023 Nov 07.
Artículo en Inglés | MEDLINE | ID: mdl-37903254

RESUMEN

Ecological divergence without geographic isolation, as an early speciation process that may lead finally to reproductive isolation through natural selection, remains a captivating topic in evolutionary biology. However, the pattern of genetic divergence underlying this process across the genome may vary between species and mating systems. Here, we present evidence that Brachypodium stacei, an annual and highly selfing grass model species, has undergone sympatric ecological divergence without geographic isolation. Genomic, transcriptomic, and metabolomic analyses together with lab experiments mimicking the two opposite environmental conditions suggest that diploid B. stacei populations have diverged sympatrically in two slopes characterized by distinct biomes at Evolution Canyon I (ECI), Mount Carmel, Israel. Despite ongoing gene flow, primarily facilitated by seed dispersal, the level of gene flow has progressively decreased over time. This local adaptation involves the scattered divergence of many unlinked loci across the total genome that include both coding genes and noncoding regions. Additionally, we have identified significant differential expressions of genes related to the ABA signaling pathway and contrasting metabolome composition between the arid- vs. forest-adapted B. stacei populations in ECI. These results suggest that multiple small loci involved in environmental responses act additively to account for ecological adaptations by this selfing species in contrasting environments.


Asunto(s)
Brachypodium , Brachypodium/genética , Diploidia , Aislamiento Reproductivo , Ecosistema , Genoma de Planta/genética , Especiación Genética
4.
Mol Biol Evol ; 40(12)2023 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-38000891

RESUMEN

Both homeologous exchanges and homeologous expression bias are generally found in most allopolyploid species. Whether homeologous exchanges and homeologous expression bias differ between repeated allopolyploid speciation events from the same progenitor species remains unknown. Here, we detected a third independent and recent allotetraploid origin for the model grass Brachypodium hybridum. Our homeologous exchange with replacement analyses indicated the absence of significant homeologous exchanges in any of the three types of wild allotetraploids, supporting the integrity of their progenitor subgenomes and the immediate creation of the amphidiploids. Further homeologous expression bias tests did not uncover significant subgenomic dominance in different tissues and conditions of the allotetraploids. This suggests a balanced expression of homeologs under similar or dissimilar ecological conditions in their natural habitats. We observed that the density of transposons around genes was not associated with the initial establishment of subgenome dominance; rather, this feature is inherited from the progenitor genome. We found that drought response genes were highly induced in the two subgenomes, likely contributing to the local adaptation of this species to arid habitats in the third allotetraploid event. These findings provide evidence for the consistency of subgenomic stability of parental genomes across multiple allopolyploidization events that led to the same species at different periods. Our study emphasizes the importance of selecting closely related progenitor species genomes to accurately assess homeologous exchange with replacement in allopolyploids, thereby avoiding the detection of false homeologous exchanges when using less related progenitor species genomes.


Asunto(s)
Brachypodium , Brachypodium/genética , Genoma de Planta , Poliploidía
5.
Anal Chem ; 96(24): 9953-9960, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38850235

RESUMEN

In traditional luminol electrochemiluminescence (ECL) systems, hydrogen peroxide (H2O2) and dissolved oxygen (DO) are the commonly used coreactants to generate reactive oxygen species (ROS) for ECL emission. However, the self-decomposition of hydrogen peroxide and the limited solubility and content of oxygen in solution undoubtedly restrict the luminescence efficiency and stability of the luminol ECL system. Inspired by the ROS-mediated ECL mechanism, we pioneered hydroxide ion as an advanced luminol ECL coreactant using nickel-doped and carbon nanotube-modified tungsten oxide (Ni-WOx-CNT) as the coreactant accelerator. Owing to the excellent catalytic activity of Ni-WOx-CNT, amounts of ROS were generated from OH- at a low excitation voltage, which subsequently reacted with luminol anion radicals and triggered intense ECL signals. Experiments confirmed an impressive ECL behavior in terms of high luminescent intensity (85,563 a.u.) and super stability over 1300 consecutive tests; both are superior to those recently reported luminol-H2O2 and luminol-DO systems with smaller ECL intensities and consecutive tests less than 25 times. To validate the feasibility and versatility of the developed system in sensor, traditional three-electrodes system and closed bipolar electrodes system with various sensing strategies of direct oxidation, "gate-effect" of molecularly imprinted polymer, immune reaction, and enzyme-catalyzed reaction were proposed to monitor uric acid (UA), C-reactive protein (CRP), immunoglobulin G (IgG), and glucose (Glu). The superior sensing performances confirmed the great application potential of the developed ROS-mediated ECL system.

6.
Anal Chem ; 96(19): 7602-7608, 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38671546

RESUMEN

Molecular imprinting techniques have attracted a lot of attention as a potential biomimetic technology, but there are still challenges in protein imprinting. Herein, multifunctional nanosized molecularly imprinted polymers (nanoMIPs) for human angiotensin-converting enzyme 2 (ACE2) were prepared by epitope imprinting of magnetic nanoparticles-anchored peptide (magNP-P) templates, which were further applied to construct a competitive displacement fluorescence assay toward ACE2. A cysteine-flanked dodecapeptide sequence was elaborately selected as an epitope for ACE2, which was immobilized onto the surface of magnetic nanoparticles and served as a magNP-P template for imprinting. During polymerization, fluorescent monomers were introduced to endow fluorescence responsiveness to the prepared self-signaling nanoMIPs. A competitive displacement fluorescence assay based on the nanoMIPs was established and operated in a washing-free manner, yielding a wide range for ACE2 (0.1-6.0 pg/mL) and a low detection limit (0.081 pg/mL). This approach offers a promising avenue in the preparation of nanoMIPs for macromolecule recognition and expands potential application of an MIP in the detection of proteins as well as peptides.


Asunto(s)
Enzima Convertidora de Angiotensina 2 , Humanos , Enzima Convertidora de Angiotensina 2/metabolismo , Enzima Convertidora de Angiotensina 2/química , Peptidil-Dipeptidasa A/metabolismo , Peptidil-Dipeptidasa A/química , Impresión Molecular , Nanopartículas de Magnetita/química , Polímeros Impresos Molecularmente/química , Límite de Detección , Péptidos/química , Péptidos/metabolismo
7.
Int Immunol ; 35(5): 243-253, 2023 05 08.
Artículo en Inglés | MEDLINE | ID: mdl-36591893

RESUMEN

Immunogenicity can be evaluated by detecting antibodies (Abs) induced by an antigen. Presently deployed assays, however, do not consider the negative impacts of Ab poly-specificity, which is well established at the monoclonal antibody level. Here, we studied antibody poly-specificity at the serum level (i.e. nonspecific Ab-probe interactions, NSIs), and ended up establishing a new platform for viral peptide immunogenicity evaluation. We first selected three peptides of high, medium and low immunogenicity, using a 'vaccine serum response rate'-based approach (i.e. the gold standard). These three peptides (Pi) in the bovine serum albumin-Pi form were used to immunize chickens, resulting in longitudinal serum samples for screening with a non-cognate peptide library. The signal intensity of Ab-peptide specific binding and 'NSI count' was used to evaluate the viral peptides' immunogenicity. Only the NSI count agreed with the gold standard. The NSI count also provides more informative data on antibody production than the aggregated signal intensity by whole-protein-based indirect enzyme-linked immunosorbent assay.


Asunto(s)
Especificidad de Anticuerpos , Inmunoglobulinas , Péptidos , Proteínas Virales , Biblioteca de Péptidos , Inmunoglobulinas/sangre , Animales , Pollos , Virus de la Enfermedad de Newcastle/inmunología , Péptidos/inmunología , Ensayo de Inmunoadsorción Enzimática , Formación de Anticuerpos , Proteínas Virales/inmunología
8.
Gastrointest Endosc ; 2024 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-38851455

RESUMEN

BACKGROUND AND AIMS: Submucosal tunneling endoscopic septum division (STESD) is a valid endoscopic modality for treating esophageal diverticula. However, it requires highly skilled endoscopists. Here we propose a modified STESD method. METHODS: This is a single center prospective case series. We consecutively enrolled 8 patients diagnosed with esophageal diverticula. All the patients underwent the modified STESD by one experienced endoscopist. RESULTS: Only one patient had intraoperative bleeding and was successfully stopped endoscopically. The size of the diverticula were 3.16 ± 1.14 cm as mean ± SD. The operation time ranged from 27 to 68 min with the mean value of 40.88 min. The number of clips ranged from 4 to 8. The success rate was 100%. None of the patients had symptom recurrences during 2 - 25 months of follow-up. CONCLUSIONS: The modified STESD method for esophageal diverticula is effective and safe, further large prospective controlled studies are needed.

9.
Arch Virol ; 169(7): 134, 2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38834736

RESUMEN

Anthrax is an acute infectious zoonotic disease caused by Bacillus anthracis, a bacterium that is considered a potential biological warfare agent. Bacillus bacteriophages shape the composition and evolution of bacterial communities in nature and therefore have important roles in the ecosystem community. B. anthracis phages are not only used in etiological diagnostics but also have promising prospects in clinical therapeutics or for disinfection in anthrax outbreaks. In this study, two temperate B. anthracis phages, vB_BanS_A16R1 (A16R1) and vB_BanS_A16R4 (A16R4), were isolated and showed siphovirus-like morphological characteristics. Genome sequencing showed that the genomes of phages A16R1 and A16R4 are 36,569 bp and 40,059 bp in length, respectively. A16R1 belongs to the genus Wbetavirus, while A16R4 belongs to the genus Hubeivirus and is the first phage of that genus found to lyse B. anthracis. Because these two phages can comparatively specifically lyse B. anthracis, they could be used as alternative diagnostic tools for identification of B. anthracis infections.


Asunto(s)
Fagos de Bacillus , Bacillus anthracis , Genoma Viral , Bacillus anthracis/virología , Genoma Viral/genética , Fagos de Bacillus/aislamiento & purificación , Fagos de Bacillus/genética , Fagos de Bacillus/clasificación , Siphoviridae/genética , Siphoviridae/aislamiento & purificación , Siphoviridae/clasificación , Filogenia
10.
Epidemiol Infect ; 152: e65, 2024 Feb 29.
Artículo en Inglés | MEDLINE | ID: mdl-38418421

RESUMEN

Contra-posing panel data on the incidence of pulmonary tuberculosis (PTB) at the provincial level in China through the years of 2004-2021 and introducing a geographically and temporally weighted regression (GTWR) model were used to explore the effect of various factors on the incidence of PTB from the perspective of spatial heterogeneity. The principal component analysis (PCA) was used to extract the main information from twenty-two indexes under six macro-factors. The main influencing factors were determined by the Spearman correlation and multi-collinearity tests. After fitting different models, the GTWR model was used to analyse and obtain the distribution changes of regression coefficients. Six macro-factors and incidence of PTB were both correlated, and there was no collinearity between the variables. The fitting effect of the GTWR model was better than ordinary least-squares (OLS) and geographically weighted regression (GWR) models. The incidence of PTB in China was mainly affected by six macro-factors, namely medicine and health, transportation, environment, economy, disease, and educational quality. The influence degree showed an unbalanced trend in the spatial and temporal distribution.


Asunto(s)
Tuberculosis Pulmonar , Humanos , China/epidemiología , Incidencia , Modelos Estadísticos , Análisis de Componente Principal , Factores de Riesgo , Análisis Espacio-Temporal , Tuberculosis Pulmonar/epidemiología
11.
Thromb J ; 22(1): 9, 2024 Jan 12.
Artículo en Inglés | MEDLINE | ID: mdl-38216919

RESUMEN

Oxidative stress is an imbalance between the body's reactive oxygen species and antioxidant defense mechanisms. Oxidative stress is involved in the development of several cardiovascular diseases, such as pulmonary hypertension, atherosclerosis, and diabetes mellitus. A growing number of studies have suggested the potential role of oxidative stress in the pathogenesis of pulmonary embolism. Biomarkers of oxidative stress in pulmonary embolism have also been explored, such as matrix metalloproteinases, asymmetric dimethylarginine, and neutrophil/lymphocyte ratio. Here, we comprehensively summarize some oxidative stress mechanisms and biomarkers in the development of acute pulmonary embolism and summarize related treatments based on antioxidant stress to explore effective treatment strategies for acute pulmonary embolism.

12.
BMC Psychiatry ; 24(1): 206, 2024 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-38486183

RESUMEN

BACKGROUND: There may be unexplored interactions between family health, personality, and smoking that could help provide new perspectives on tobacco control. OBJECTIVE: To examine the relationship between the health of one's family and their smoking habits, as well as investigate the potential influence of personality on this relationship. METHODS: For this cross-sectional investigation, a national survey conducted in China in 2022 recruited a total of 21,916 individuals. The Family Health Scale was utilized to assess the health of the family. The 10-item Big Five Inventory scale was utilized to assess the Big five personality traits. The relationship between big five personality, family health, and smoking were investigated using binary and linear logistic regression. The indirect effects mediated by Big five personality were analyzed using mediation analysis with Sobel tests, and the indirect effects were composited using the Karlson-Holm-Breen method. RESULTS: The overall prevalence of smoking in the study population was 14.87%, 26.19% for males and 3.54% for females. Urban and rural smoking prevalence was 13.81% and 16.10% respectively. Binary logistic regression analysis revealed a significant negative relationship between smoking and family health (odds ratio 0.964, 95% CI 0.959, 0.970, P < 0.001) with covariates controlled. The Karlson-Holm-Breen composition facilitated the connection between extraversion (47.81%) and nervousness (52.19%). CONCLUSIONS: Preventive interventions for smoking behavior should prioritize family health and the Big five personality as significant areas to focus on. According to this study, in addition to implementing various interventions for different personalities, family health should be strengthened to reduce smoking behavior.


Asunto(s)
Pueblos del Este de Asia , Salud de la Familia , Personalidad , Masculino , Femenino , Humanos , Estudios Transversales , Fumar/epidemiología
13.
J Environ Manage ; 352: 120109, 2024 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-38232586

RESUMEN

Colloidal phosphorus (P) is an important P form in agricultural runoff and can threaten water quality. However, up to date, there are few effective approaches to mitigate colloidal P pollution. This study investigated the effect of ultraviolet (UV) irradiation on medium-colloidal (MC; 220 nm-450 nm) and fine-colloidal (FC; 3 kDa-220 nm) P in agricultural runoff. Under 24 h of UV irradiation, as the most abundant colloidal P fraction, concentration of total P (TP) in FC consistently decreased by 81.0%, while TP concentration in MC first increased by 74.4% after 3 h and then decreased with irradiation time. At the same time, particulate TP (>450 nm) concentration was found to be increased from 0 to 14.7 µM. However, there were no obvious variations in TP concentrations in FC and MC fractions under dark conditions. In FC fraction, with the decrease of TP, the corresponding concentrations of iron (Fe), aluminum (Al), silicon (Si) declined synchronously, and ferric iron/ferrous iron (Fe(III)/Fe(II)) ratio and organic matter (OM) concentration were reduced as well. These results suggested that P in FC fraction was gradually transformed into particulate P during photoreduction of Fe(III) and photodegradation of OM under UV irradiation. Our study helps to understand the mechanism of the phototransformation of colloidal P, and propose an UV irradiation-based approach to remove colloidal P in agricultural runoff.


Asunto(s)
Compuestos Férricos , Fósforo , Fósforo/análisis , Agricultura , Calidad del Agua , Hierro
14.
Anal Chem ; 95(13): 5807-5814, 2023 04 04.
Artículo en Inglés | MEDLINE | ID: mdl-36946074

RESUMEN

Accurate and in-time detection of bacteria conduces to preventing their rapid spread around the environment, while a nucleic acid test (NAT) is a powerful tool for early diagnosis of pathogens. Herein, we propose a hybridization chain reaction (HCR)-mediated multisite exonuclease III (Exo-III) amplification strategy (HCR/Exo-III amplifier) to achieve the one-pot and ultrasensitive isothermal amplification of bacterial 16S rRNA and a portable fluorescence detection device (PFD) to directly read signals in a lateral flow assay (LFA). In detail, the target-initiated HCR products present multiple binding sites for triggering the Exo-III amplifier that produces numerous target amplicons. Following that, the target amplicons travel up on the strip and bridge between the DNA-CdTe/CdS probes and the capture DNA to form a positive fluorescence line. After that, the strip is inserted into the PFD to accomplish the fluorescence signal reading. The constructed HCR/Exo-III amplifier-based PFD-LFA implemented the simultaneous and specific detection of three bacteria with a detection limit of a few tenths of fM for synthetic 16S rRNA fragments and dozens of CFU/mL for Staphylococcus aureus, Listeria monocytogenes, and Salmonella typhimurium in pure cultures. The sensing platform features isothermal amplification, convenient operation, and good economy, displaying great potential for on-site testing toward multiple nucleic acid analytes.


Asunto(s)
Técnicas Biosensibles , Compuestos de Cadmio , Puntos Cuánticos , ARN Ribosómico 16S/genética , Telurio , Hibridación de Ácido Nucleico , ADN/química , Exodesoxirribonucleasas/metabolismo , Sondas de ADN , Técnicas de Amplificación de Ácido Nucleico/métodos , Límite de Detección , Técnicas Biosensibles/métodos
15.
BMC Neurosci ; 24(1): 10, 2023 01 31.
Artículo en Inglés | MEDLINE | ID: mdl-36721107

RESUMEN

BACKGROUND: Glioblastoma (GBM) is the most common malignant intracranial tumor with a low survival rate. However, only few drugs responsible for GBM therpies, hence new drug development for it is highly required. The natural product Cudraflavone B (CUB) has been reported to potentially kill a variety of tumor cells. Currently, its anit-cancer effect on GBM still remains unknown. Herein, we investigated whether CUB could affect the proliferation and apoptosis of GBM cells to show anti-GBM potential. RESULTS: CUB selectively inhibited cell viability and induced cell apoptosis by activating the endoplasmic reticulum stress (ER stress) related pathway, as well as harnessing the autophagy-related PI3K/mTOR/LC3B signaling pathway. Typical morphological changes of autophagy were also observed in CUB treated cells by microscope and scanning electron microscope (SEM) examination. 4-Phenylbutyric acid (4-PBA), an ER stress inhibitor, restored the CUB-caused alteration in signaling pathway and morphological change. CONCLUSIONS: Our finding suggests that CUB impaired cell growth and induced cell apoptosis of glioblastoma through ER stress and autophagy-related signaling pathways, and it might be an attractive drug for treatment of GBM.


Asunto(s)
Glioblastoma , Humanos , Glioblastoma/tratamiento farmacológico , Autofagia , Apoptosis , Estrés del Retículo Endoplásmico
16.
J Med Virol ; 95(10): e29186, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37855656

RESUMEN

To the best of our knowledge, no previous study has quantitatively estimated the dynamics and cumulative susceptibility to influenza infections after the widespread lifting of COVID-19 public health measures. We constructed an imitated stochastic susceptible-infected-removed model using particle-filtered Markov Chain Monte Carlo sampling to estimate the time-dependent reproduction number of influenza based on influenza surveillance data in southern China, northern China, and the United States during the 2022-2023 season. We compared these estimates to those from 2011 to 2019 seasons without strong social distancing interventions to determine cumulative susceptibility during COVID-19 restrictions. Compared to the 2011-2019 seasons without a strong intervention with social measures, the 2022-2023 influenza season length was 45.0%, 47.1%, and 57.1% shorter in southern China, northern China, and the United States, respectively, corresponding to an 140.1%, 74.8%, and 50.9% increase in scale of influenza infections, and a 60.3%, 72.9%, and 45.1% increase in population susceptibility to influenza. Large and high-intensity influenza epidemics occurred in China and the United States in 2022-2023. Population susceptibility increased in 2019-2022, especially in China. We recommend promoting influenza vaccination, taking personal prevention actions on at-risk populations, and monitoring changes in the dynamic levels of influenza and other respiratory infections to prevent potential outbreaks in the coming influenza season.


Asunto(s)
COVID-19 , Gripe Humana , Humanos , Estados Unidos/epidemiología , Gripe Humana/epidemiología , Gripe Humana/prevención & control , COVID-19/epidemiología , Estaciones del Año , Pandemias , China/epidemiología
17.
BMC Cancer ; 23(1): 103, 2023 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-36717797

RESUMEN

BACKGROUND: Real-world data of Palbociclib are insufficient in China. This study aimed to investigate the treatment pattern and real-world outcomes in hormone receptor positive and human epidermal growth factor 2 receptor negative (HR+/HER2-) metastatic breast cancer (MBC) patients treated with Palbociclib in the northwest of China. METHODS: HR+/HER2- MBC patients who received Palbociclib in 8 centers from July 2017 to September 2019 were retrospectively included in this study. Real-world objective response rate (ORR), progression-free survival (PFS) and safety profiles were analyzed. The survival curves were plotted by the Kaplan-Meier method to analyze PFS, which was verified by the log-rank test. RESULTS: In total, 211 women were eligible for the analysis. A total of 85 patients (40.3%), 78 (37.0%), and 48 (22.7%) received Palbociclib in the first-, second-, third- or later-line setting, respectively. 46 patients achieved partial response and 145 patients experienced stable disease, with an ORR of 21.8% and a disease control rate of 90.5%. Following a median follow-up period of 14.2 months, the median PFS was 12.2 months (95% confidence interval, 10.1-14.3 m), and the median overall survival was not reached. Early Palbociclib initiation, sensitivity or acquired resistance to endocrine therapy, estrogen receptor and progesterone receptor double positivity, less than 3 metastatic sites, without visceral metastasis, bone metastasis only, without prior chemotherapy or endocrine therapy were associated with a prolonged PFS in MBC (All P < 0.05). The most common grade 3 or 4 adverse events (AE) was neutropenia (36.5%), and the most common nonhematologic AE was fatigue (10.9%). No patient experienced AE leading to treatment discontinuation. CONCLUSION: Palbociclib plus endocrine therapy exhibited favorable effectiveness and manageable toxicities in the real-world setting, supporting their use in Chinese patients with HR+/HER2 - MBC.


Asunto(s)
Neoplasias de la Mama , Femenino , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Receptor ErbB-2/metabolismo , Estudios Retrospectivos
18.
BMC Cancer ; 23(1): 662, 2023 Jul 14.
Artículo en Inglés | MEDLINE | ID: mdl-37452291

RESUMEN

BACKGROUND: Clinical studies have shown that first-line use of anti-angiogenetic therapy can prolong progression-free survival but little progress has been made in extending the overall survival of the patients. We explored the role of ELK3 in glioma angiogenesis to improve and design more efficacious therapies. METHODS: A tissue microarray and immunohistochemistry analysis were used to determine the expression of ELK3 protein in 400 glioma patients. Cell proliferation, metastasis, cell cycle, and apoptosis were monitored in U87 and U251 cells using CCK-8, EdU, transwell assays, and flow cytometry. A tube-formation assay, a rat aorta ring sprouting assay, and a matrigel plug assay were performed to examine the antiangiogenic activity of ELK3. An ELISA, Western blot, and correlation analysis of the CGGA dataset were used to detect the association between ELK3 and VEGF-A or ELK3 and HIF-1[Formula: see text]. Besides, orthotopic transplantation in nude mice and histopathological and immunological analysis of in vitro tumors were used to explore the effect of ELK3 on tumor progression and median survival. RESULTS: ELK3 was upregulated in glioma tissues and associated with a poor prognosis. In vitro, ELK3 promoted cell proliferation and cell cycle progression, induced metastasis, and suppressed apoptosis. Then, silencing ELK3 inhibited VEGF-A expression and secretion by facilitating HIF-1[Formula: see text] degradation via ubiquitination. Finally, knockdown ELK3 inhibited tumor progression and angiogenesis in vitro and in vivo, as well as prolonged nude mice's median survival. CONCLUSIONS: Our findings first evidenced that ELK3 is crucial for glioma because it promotes angiogenesis by activating the HIF-1[Formula: see text]/VEGF-A signaling axis. Therefore, we suggest that ELK3 is a prognostic marker with a great potential for glioma angiogenesis and ELK3-targeted therapeutic strategies might hold promise in improving the efficacy of anti-angiogenic therapies.


Asunto(s)
Glioma , Factor A de Crecimiento Endotelial Vascular , Animales , Ratones , Ratones Desnudos , Factor A de Crecimiento Endotelial Vascular/metabolismo , Glioma/patología , Transducción de Señal , Proliferación Celular , Factor 1 Inducible por Hipoxia/metabolismo , Línea Celular Tumoral , Neovascularización Patológica/metabolismo
19.
Pulm Pharmacol Ther ; 83: 102251, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37666296

RESUMEN

BACKGROUND: Airway epithelial cells epithelial mesenchymal transition (EMT) and lung fibroblasts extracellular matrix (ECM) production are the key steps in airway remodeling. Our previous study demonstrated that miR-143-3p has the ability to impede airway smooth muscle cell proliferation and ECM deposition. However, the function of miR-143-3p in airway epithelial cells and lung fibroblasts remains unclear. METHODS: Cell viability was determined using MTT method, while cell migration was evaluated through scratch assay. EMT and ECM proteins were detected by western blot, RT-qPCR, and ELISA. To determine the level of miR-143-3p m6A methylation, we employed the meRIP-qPCR assay. Additionally, the binding of miR-143-3p with Smad3 were projected by bioinformatics and validated by dual luciferase reporter assays. RESULTS: It was discovered that the expression of miR-143-3p were lower in both asthma patients and TGF-ß1-treated human bronchial epithelial 16HBE cells and human lung fibroblast HPF cells. Upregulation of miR-143-3p restrained 16HBE cell migration, and decreased EMT mesenchymal markers and increased epithelial markers. And upregulation of miR-143-3p impaired cell viability and ECM protein production in HPF cells. Mechanistically, interfering with METTL3 resulted in decreased m6A modification of miR-143-3p and led to lower levels of miR-143-3p. Moreover, miR-143-3p were verified to directly target and downregulate Smad3. Upregulation of Smad3 attenuated the effects of miR-143-3p on cell EMT and ECM production. CONCLUSION: MiR-143-3p inhibits airway epithelial cell EMT as well as lung fibroblast ECM production by downregulating Smad3. Therefore, miR-143-3p may be a promising target to reduce airway remodeling in asthma.


Asunto(s)
Asma , MicroARNs , Humanos , Remodelación de las Vías Aéreas (Respiratorias) , Asma/metabolismo , Movimiento Celular , Proliferación Celular , Células Epiteliales/metabolismo , Transición Epitelial-Mesenquimal , Matriz Extracelular/metabolismo , Pulmón/metabolismo , Metiltransferasas/metabolismo , MicroARNs/genética , Factor de Crecimiento Transformador beta1/metabolismo
20.
BMC Infect Dis ; 23(1): 763, 2023 Nov 06.
Artículo en Inglés | MEDLINE | ID: mdl-37932657

RESUMEN

BACKGROUND: Common air pollutants such as ozone (O3), sulfur dioxide (SO2), nitrogen dioxide (NO2), and particulate matter play significant roles as influential factors in influenza-like illness (ILI). However, evidence regarding the impact of O3 on influenza transmissibility in multi-subtropical regions is limited, and our understanding of the effects of O3 on influenza transmissibility in temperate regions remain unknown. METHODS: We studied the transmissibility of influenza in eight provinces across both temperate and subtropical regions in China based on 2013 to 2018 provincial-level surveillance data on influenza-like illness (ILI) incidence and viral activity. We estimated influenza transmissibility by using the instantaneous reproduction number ([Formula: see text]) and examined the relationships between transmissibility and daily O3 concentrations, air temperature, humidity, and school holidays. We developed a multivariable regression model for [Formula: see text] to quantify the contribution of O3 to variations in transmissibility. RESULTS: Our findings revealed a significant association between O3 and influenza transmissibility. In Beijing, Tianjin, Shanghai and Jiangsu, the association exhibited a U-shaped trend. In Liaoning, Gansu, Hunan, and Guangdong, the association was L-shaped. When aggregating data across all eight provinces, a U-shaped association was emerged. O3 was able to accounted for up to 13% of the variance in [Formula: see text]. O3 plus other environmental drivers including mean daily temperature, relative humidity, absolute humidity, and school holidays explained up to 20% of the variance in [Formula: see text]. CONCLUSIONS: O3 was a significant driver of influenza transmissibility, and the association between O3 and influenza transmissibility tended to display a U-shaped pattern.


Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire , Gripe Humana , Ozono , Humanos , Ozono/análisis , Contaminación del Aire/análisis , China/epidemiología , Gripe Humana/epidemiología , Contaminantes Atmosféricos/análisis
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