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1.
Animals (Basel) ; 14(17)2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39272367

RESUMEN

In this study, sixteen Sprague Dawley (SD) female rats and eight SD male rats were co-housed to mate. Pregnant SD female rats were fed with a control diet or an MA diet. Breast milk, maternal ileum, and intestinal samples of the offspring were collected at the day of birth and ten days afterwards. The results showed that the impact of MA was more obvious on the microbiota of mature milk (p = 0.066) than on that of colostrum. In addition, MA additive did not significantly affect maternal ileal microbiota, but affected offsprings' colonic microbiota significantly ten days after birth (p = 0.035). From the day of giving birth to ten days afterwards, in addition to the increase in microbial richness and diversity, at genus level, the dominant bacteria of breastmilk changed from Pseudomonas veronii to Bacillus and Lactococcus. Different from breastmilk microbiota, ten days after giving birth, the maternal ileal microbiota and the offsprings' intestinal microbiota were dominated by Lactobacillus. Instead of ileal microbiota, offsprings' colonic microbiota is a key action site of maternal MA additive. Therefore, the current findings have significant implications for the development of maternal feed aimed at modulating the intestinal microbiota of offspring, ultimately leading to improved health outcomes for both mothers and their offspring.

2.
BMC Cancer ; 24(1): 948, 2024 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-39095810

RESUMEN

BACKGROUND: Hepatoid adenocarcinoma of the lung (HAL) is a distinctly uncommon subtype of lung adenocarcinoma (LAC), characterized by hepatoid features and an alarmingly low 5-year survival rate of approximately 8%. The scarcity of information on this condition has contributed to the absence of standardized treatment protocols, and the molecular underpinnings of its pathogenesis remain largely unexplored. To bridge these gaps, this study compiled data from 191 primary HAL patients to delineate treatment patterns, prognostic factors, and potential pathogenic mechanisms. METHODS: This study was divided into two cohorts: cohort 1, comprising 110 patients extracted from the Surveillance, Epidemiology, and End Results (SEER) database, and cohort 2, consisting of 70 patients identified through a comprehensive literature review via the PubMed, Web of Science, and Scopus databases, in addition to 11 patients from Tongji Hospital. The Cox proportional hazards regression model was employed to identify independent prognostic factors. Kaplan-Meier survival curves were generated to assess the impact of treatment modalities centered around surgery and chemotherapy. Moreover, this study evaluated the efficacy of first-line treatment regimens and conducted Gene Ontology function and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses on identified mutated genes. RESULTS: The demographic and clinical profile of HAL patients typically comprises older individuals who are smokers, with a predisposition for diagnosis at advanced disease stages, culminating in a high mortality rate. Key prognostic indicators identified included disease stage, chemotherapy and surgical interventions. The study suggests a treatment strategy that advocates chemotherapy for patients with stage IV HAL and surgery for those with non-stage IV disease. The combination of paclitaxel and platinum-based chemotherapy emerged as an efficacious first-line treatment, with the integration of immunotherapy and targeted therapies showing potential benefits. Genetic analysis underscored similarities between HAL and LAC, particularly highlighting aberrant kinase activity (serine, threonine, and tyrosine) and the activation of PI3K-Akt and MAPK signaling pathways as contributing factors to HAL pathogenesis. CONCLUSION: Despite its relatively rare occurrence, this study underscores the significance of treatment strategies and concludes probable prognostic factors. Due to limited reports, a deeper understanding of the molecular mechanisms driving tumorigenesis and progression in HAL is needed.


Asunto(s)
Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Humanos , Masculino , Femenino , Adenocarcinoma del Pulmón/terapia , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/patología , Adenocarcinoma del Pulmón/mortalidad , Persona de Mediana Edad , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/tratamiento farmacológico , Anciano , Pronóstico , Programa de VERF , Adulto , Estimación de Kaplan-Meier , Tasa de Supervivencia
3.
Int J Ophthalmol ; 17(8): 1453-1461, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39156772

RESUMEN

AIM: To quantitatively assess the changes in mean vascular tortuosity (mVT) and mean vascular width (mVW) around the optic disc and their correlation with gestational age (GA) and birth weight (BW) in premature infants without retinopathy of prematurity (ROP). METHODS: A single-center retrospective study included a total of 133 (133 eyes) premature infants [mean corrected gestational age (CGA) 43.6wk] without ROP as the premature group and 130 (130 eyes) CGA-matched full-term infants as the control group. The peripapillary mVT and mVW were quantitatively measured using computer-assisted techniques. RESULTS: Premature infants had significantly higher mVT (P=0.0032) and lower mVW (P=0.0086) by 2.68 (104 cm-3) and 1.85 µm, respectively. Subgroup analysis with GA showed significant differences (P=0.0244) in mVT between the early preterm and middle to late preterm groups, but the differences between mVW were not significant (P=0.6652). The results of the multiple linear regression model showed a significant negative correlation between GA and BW with mVT after adjusting sex and CGA (P=0.0211 and P=0.0006, respectively). For each day increase in GA at birth, mVT decreased by 0.1281 (104 cm-3) and for each 1 g increase in BW, mVT decreased by 0.006 (104 cm-3). However, GA (P=0.9402) and BW (P=0.7275) were not significantly correlated with mVW. CONCLUSION: Preterm birth significantly affects the peripapillary vascular parameters that indicate higher mVT and narrower mVW in premature infants without ROP. Alterations in these parameters may provide new insights into the pathogenesis of ocular vascular disease.

4.
Angew Chem Int Ed Engl ; : e202412964, 2024 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-39048539

RESUMEN

High efficiently photocatalytic CO2 reduction (CO2RR) into liquid fuels in pure water system remains challenged. Iron polyphthalocyanine (FePPc) with strong light harvesting, unique Fe-N4 structure, abundant pores, and good stability could serve as a promising catalyst for CO2 photoreduction. To further improve the catalytic efficiency, herein, symmetry-breaking Fe sites are constructed by coupling with atomically precise M1Ag24 (M=Ag, Au, Pt) series clusters. Especially, the introduction of Pt1Ag24 causes the most asymmetric charge distribution of Fe in FePPc (followed by Au1Ag24 and Ag25), leading to the favorable CO2 adsorption and activation. In addition, Pt1Ag24-FePPc exhibits the most effective photogenerated carriers transfer and separation. As a result, Pt1Ag24-FePPc shows the methanol/ethanol yield of 48.55/32.97 µmol·gcat-1·h-1 in H2O-CO2 system under visible light irradiation, ~ 1.65/1.25-fold, 1.83/1.37-fold, and 3.6/1.61-fold higher than that of Au1Ag24-FePPc, Ag25-FePPc, and FePPc, respectively. This work provides a concept for precisely construction and regulation symmetry-breaking sites of cluster-based catalysts for effective CO2 conversion.

5.
Front Pharmacol ; 15: 1431579, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39045045

RESUMEN

Objective: This study aimed to explore the neurological adverse events of oxaliplatin through the Food and Drug Administration Adverse Event Reporting System (FAERS) database and to provide reference for safe clinical drug use. Methods: The adverse events report data of oxaliplatin from the first quarter of 2019 (1 January 2019) to the third quarter of 2023 (30 September 2023) were extracted from FAERS database, and the adverse events signal intensity was determined using the reporting odds ratio, proportional reporting ratio, information component, and empirical Bayes geometric mean methods. Time-to-onset and univariate logistic regression analysis were performed to describe the characteristics and risk factors of oxaliplatin-associated neurological adverse events. Results: A total of 4,471 cases of oxaliplatin-associated neurological adverse events were identified, with 318 neurological adverse events being documented, among which 87 adverse events satisfied the thresholds of four methodologies. The median time-to-onset of oxaliplatin-associated neurological adverse events was 2 days (interquartile range 0-36 days). Among the factors significantly influencing oxaliplatin-related neurological adverse events, male sex and combination medication decreased the risk of neurological adverse events, while higher cumulative dose increased the risk. Conclusion: The real-world neurotoxicity spectrum of oxaliplatin and its characteristics and influencing factors were obtained through data mining of FAERS, providing valuable insights for healthcare professionals to effectively manage the risk of neurological adverse events associated with oxaliplatin in clinical practice.

6.
Biomed Opt Express ; 15(6): 3727-3742, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38867776

RESUMEN

In digital holographic microscopy (DHM), achieving large field of view (FOV) imaging while maintaining high resolution is critical for quantitative phase measurements of biological cell tissues and micro-nano structures. We present a quantitative phase image stitching guided by reconstructed intensity images in one-shot double FOV multiplexed DHM. Double FOVs are recorded simultaneously through frequency division multiplexing; intensity feature pairs are accurately extracted by multi-algorithm fusion; aberrations and non-common baselines are effectively corrected by preprocessing. Experimental results show that even if phase images have coherent noise, complex aberrations, low overlap rate and large size, this method can achieve high-quality phase stitching.

7.
Foods ; 13(11)2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-38890954

RESUMEN

Prickly ash peel oleoresin (PPO) is a highly concentrated oil of Prickly ash essential oil and has a stronger aroma. However, its low water solubility, high volatility, difficulty in transport and storage, and decomposition by light, heat, and oxygen limit its wider application. To solve this problem, this study used freeze-drying or spray-drying, with soybean protein isolate (SPI) or gum Arabic (GA), combined with aqueous maltodextrin (MD) as the encapsulating agents to prepare four types of PPO microcapsules (POMs). Spray-dried microcapsules with GA as the encapsulating agent achieved a high encapsulation efficiency (EE) of 92.31 ± 0.31%, improved the thermal stability of the PPO, and had spherical morphology. (Headspace solid-phase microextraction/gas chromatography-mass spectrometry) HS-SPME/GC-MS detected 41 volatile compounds in PPO; of these, linalool, ß-myrcene, sabinene, and D-limonene were identified as key flavor components. Principal component analysis (PCA) effectively distinguished the significant differences in flavor between PPO, spray-dried SPI/MD microcapsules (SS), and spray-dried GA/MD microcapsules (SG). During 15 days of air-exposure, the loss of flavor from SG (54.62 ± 0.54%) was significantly lower than PPO (79.45 ± 1.45%) and SS (57.55 ± 0.36%). During the air-exposure period, SG consistently had the highest antioxidant capacity, making it desirable for PPO packaging, and expanding its potential applications within the food industry.

8.
Int J Ophthalmol ; 17(3): 420-434, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38721513

RESUMEN

AIM: To explore whether autophagy functions as a cellular adaptation mechanism in lens epithelial cells (LECs) under hyperosmotic stress. METHODS: LECs were treated with hyperosmotic stress at the concentration of 270, 300, 400, 500, or 600 mOsm for 6, 12, 18, 24h in vitro. Polymerase chain reaction (PCR) was employed for the mRNA expression of autophagy-related genes, while Western blotting detected the targeted protein expression. The transfection of stub-RFP-sens-GFP-LC3 autophagy-related double fluorescence lentivirus was conducted to detect the level of autophagy flux. Scanning electron microscopy was used to detect the existence of autolysosome. Short interfering RNA of autophagy-related gene (ATG) 7, transient receptor potential vanilloid (TRPV) 1 overexpression plasmid, related agonists and inhibitors were employed to their influence on autophagy related pathway. Flow cytometry was employed to test the apoptosis and intracellular Ca2+ level. Mitochondrial membrane potential was measured by JC-1 staining. The cell counting kit-8 assay was used to calculate the cellular viability. The wound healing assay was used to evaluate the wound closure rate. GraphPad 6.0 software was utilized to evaluate the data. RESULTS: The hyperosmotic stress activated autophagy in a pressure- and time-dependent manner in LECs. Beclin 1 protein expression and conversion of LC3B II to LC3B I increased, whereas sequestosome-1 (SQSTM1) protein expression decreased. Transient Ca2+ influx was stimulated caused by hyperosmotic stress, levels of mammalian target of rapamycin (mTOR) phosphorylation decreased, and the level of AMP-activated protein kinase (AMPK) phosphorylation increased in the early stage. Based on this evidence, autophagy activation through the Ca2+-dependent AMPK/mTOR pathway might represent an adaptation process in LECs under hyperosmotic stress. Hyperosmotic stress decreased cellular viability and accelerated apoptosis in LECs and cellular migration decreased. Inhibition of autophagy by ATG7 knockdown had similar results. TRPV1 overexpression increased autophagy and might be crucial in the occurrence of autophagy promoted by hyperosmotic stress. CONCLUSION: A combination of hyperosmotic stress and autophagy inhibition may be a promising approach to decrease the number of LECs in the capsular bag and pave the way for improving prevention of posterior capsular opacification and capsular fibrosis.

9.
Discov Oncol ; 15(1): 168, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38750182

RESUMEN

BACKGROUND: Studies evaluating the effectiveness of immune checkpoint inhibitors (ICI) for endometrial cancer (EC) are limited. This study aimed to assess the efficacy of PD-1/PD-L1 inhibitors as monotherapy for EC by conducting a meta-analysis. The predictive significance of MMR status, a biomarker for ICI response, also required further investigation. METHODS: A systematic literature search was conducted in English databases until September 2023. The analysis included objective response rate (ORR), disease control rate (DCR), adverse events (AEs), and odds ratios (OR), along with their corresponding 95% confidence intervals (CI). RESULTS: There were twelve trials totaling 685 individuals. PD-1/PD-L1 inhibitor monotherapy resulted in an ORR for 34% (95% CI = 24-44%) of the pooled EC patients. Subgroup analysis revealed a significantly higher ORR in dMMR EC (45%) compared to pMMR EC (8%), with an OR of 6.36 (95% CI = 3.64-11.13). The overall DCR was 42%, with dMMR EC at 51% and pMMR EC at 30% (OR = 2.61, 95% CI = 1.69-4.05). Grade three or higher adverse events (AEs) occurred in 15% of cases (95% CI = 9-24%) of the pooled incidence of AEs, which was 68% (95% CI = 65-72%). CONCLUSIONS: This meta-analysis provides significant evidence for the effectiveness of PD-1/PD-L1 inhibitors as monotherapy for EC. Notably, dMMR EC patients demonstrated superior treatment efficacy with PD-1/PD-L1 inhibitor immunotherapy. Further research is required to explore subclassifications of EC based on dMMR molecular subtypes, enabling improved treatment strategies and outcomes for EC patients.

10.
Int J Clin Pharmacol Ther ; 62(7): 311-318, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38660885

RESUMEN

OBJECTIVE: To investigate the incidence of and risk factors for potential drug-drug interactions (DDIs) among elderly patients with corona virus disease 2019 (-COVID-19) in hospital and to explore management strategies to reduce the occurrence of potential DDIs and ensure patient medication safety. MATERIALS AND METHODS: This was a descriptive, retrospective cross-sectional study among patients aged 65 years and older who were hospitalized with COVID-19. Potential DDIs associated with prescriptions containing two or more medicines were analyzed with Lexicomp software, the incidence of DDIs was calculated, recommendations for medication adjustment were formulated, and the χ2-test and binary logistic regression were used to analyze related risk factors. RESULTS: A total of 772 prescriptions were analyzed, 527 (68.26) of which involved 5,732 potential DDIs. The results of this study showed that a total of 152 (28.84%) prescriptions had 270 X risk class potential DDIs (i.e., avoid combining), 313 (59.39%) prescriptions had 1,161 D risk class potential DDIs (i.e., consider therapy modification), and 476 (90.32%) prescriptions had 4,301 C risk class potential DDIs (i.e., monitor therapy). The study findings showed that the total number of drugs (p < 0.001), the length of hospital stay (p < 0.001), and the number of comorbidities (p < 0.001) were risk factors affecting the occurrence of potential DDIs. CONCLUSION: This study identified factors associated with potential DDIs, which can assist in changing medication strategies, preventing adverse drug reactions, and improving clinical efficacy.


Asunto(s)
Tratamiento Farmacológico de COVID-19 , COVID-19 , Interacciones Farmacológicas , Humanos , Estudios Transversales , Anciano , Estudios Retrospectivos , Masculino , Femenino , Factores de Riesgo , COVID-19/epidemiología , COVID-19/prevención & control , Anciano de 80 o más Años , Polifarmacia , Hospitalización/estadística & datos numéricos , SARS-CoV-2 , Incidencia
11.
BMC Womens Health ; 24(1): 215, 2024 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-38570811

RESUMEN

BACKGROUND: More than 2 billion women are experiencing the menopausal transition in China, and some of these women have hypertension. Limited studies has focused on perimenopausal syndrome and hypertension in a specific population, so we aimed to investigate the prevalence of perimenopausal syndrome and hypertension and to analyse their relationships and risk factors in perimenopausal women in South China. METHODS: This cross-sectional study included 3553 women aged 40 to 60 years from South China. We collected medical report, lifestyle, blood sample, general condition questionnaire, and modified Kupperman index (mKMI) data. Multivariate logistic regression analysis was performed to identify risk factors for perimenopausal syndrome and hypertension during perimenopause. RESULTS: The prevalence of hypertension in perimenopause patients was 16.58%, and the prevalence of perimenopausal syndrome was 9.9%. Compared with women without hypertension during perimenopause, women with HTN during perimenopause had an increased risk of perimenopausal syndrome (26.4% vs. 8.7%, P < 0.001). Lipid levels and urinary tract infections were risk factors for hypertension and perimenopausal syndrome, in addition to the presence of breast nodules, the intake of snacks at night, high-salt diets, red meat and sugar-sweetened beverages, and a history of smoking and drinking for perimenopausal syndrome and the presence of gestational hypertension and diabetes for hypertension. CONCLUSION: We concluded that perimenopausal syndrome and HTN are common in perimenopausal women in South China, and the associations between them are strong and positive. Perimenopausal syndrome shares some common risk factors with HTN during perimenopause, such as BMI and dyslipidaemia. Therefore, gynaecological endocrinologists in China should consider screening for perimenopausal syndrome in hypertensive perimenopausal women, and appropriate management of perimenopause is needed to alleviate these conditions.


Asunto(s)
Hipertensión , Perimenopausia , Femenino , Humanos , Prevalencia , Estudios Transversales , Factores de Riesgo , Hipertensión/epidemiología , China/epidemiología
12.
J Environ Manage ; 356: 120632, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38531129

RESUMEN

To provide a sufficient supply of electron donors for the synthesis of caproic acid, yeast fermentation was employed to increase ethanol production in the anaerobic fermentation of Chinese cabbage waste (CCW). The results showed that the caproic acid yield of CCW with ethanol pre-fermentation was 7750.3 mg COD/L, accounting for 50.2% of the total volatile fatty acids (TVFAs), which was 32.5% higher than that of the CCW without yeast inoculation. The synchronous fermentation of yeast and seed sludge significantly promoted the growth of butyric acid consuming bacterium Bacteroides, resulting in low yields of butyric acid and caproic acid. With yeast inoculation, substrate competition for the efficient ethanol conversion in the early stage of acidogenic fermentation inhibited the hydrolysis and acidfication. Without yeast inoculation, the rapid accumulation of TVFAs severely inhibited the growth of Bacteroidetes. In the reactor with ethanol pre-fermentation, the key microorganism for caproic acid production, Clostridium_sensu_stricto_12, was selectively enriched.


Asunto(s)
Brassica , Microbiota , Fermentación , Caproatos , Saccharomyces cerevisiae , Anaerobiosis , Ácidos Grasos Volátiles , Aguas del Alcantarillado/química , Butiratos , Etanol , Concentración de Iones de Hidrógeno , Reactores Biológicos
13.
Brain Behav ; 14(1): e3387, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-38376033

RESUMEN

INTRODUCTION: Gut microbiota dysbiosis is a key factor of the pathogenesis of post-stroke depression (PSD). PSD is associated with increased hippocampal neuronal apoptosis and decreased synaptic connectivity. Inulin can be involved in hippocampal neuron protection through the microbiome-gut-brain axis. However, the neuroprotective effects of inulin in PSD are still to be further investigated. METHODS: By utilizing the GEO public database, we identify differentially expressed genes in the hippocampus following inulin intake. This can help us discover key signaling pathways through functional enrichment analysis. Furthermore, we validate the expression levels of signaling molecules in a rat model of PSD and examine the effects of inulin on behavioral changes and body weight. Additionally, conducting a microbiome analysis to identify significantly different microbial populations and perform correlation analysis. RESULTS: The intake of inulin significantly up-regulated mitogen-activated protein kinase signaling pathway in the hippocampus. Inulin changed in the gut microbiota structure, leading to an increase in the abundance of Lactobacillus and Clostridium_sensu_stricto_1 in the intestines of PSD rats, while decreasing the abundance of Ruminococcus UCG_005, Prevotella_9, Oscillospiraceae, and Clostridia UCG_014. Furthermore, the inulin diet elevated levels of insulin-like growth factor 1 in the serum, which showed a positive correlation with the abundance of Lactobacillus. Notably, the consumption of inulin-enriched diet increased activity levels and preference for sugar water in PSD rats, while also reducing body weight. CONCLUSION: These findings highlight the potential therapeutic benefits of inulin in the management of depression and emphasize the importance of maintaining a healthy gut microbiota for PSD.


Asunto(s)
Microbioma Gastrointestinal , Inulina , Sistema de Señalización de MAP Quinasas , Animales , Ratas , Peso Corporal , Factor I del Crecimiento Similar a la Insulina/metabolismo , Inulina/farmacología , Transducción de Señal
14.
Nat Commun ; 15(1): 966, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38302493

RESUMEN

The tumor microenvironment is reprogrammed by cancer cells and participates in all stages of tumor progression. Neutral ceramidase is a key regulator of ceramide, the central intermediate in sphingolipid metabolism. The contribution of neutral ceramidase to the reprogramming of the tumor microenvironment is not well understood. Here, we find that deletion of neutral ceramidase in multiple breast cancer models in female mice accelerates tumor growth. Our result show that Ly6C+CD39+ tumor-infiltrating CD8 T cells are enriched in the tumor microenvironment and display an exhausted phenotype. Deletion of myeloid neutral ceramidase in vivo and in vitro induces exhaustion in tumor-infiltrating Ly6C+CD39+CD8+ T cells. Mechanistically, myeloid neutral ceramidase is required for the generation of lipid droplets and for the induction of lipolysis, which generate fatty acids for fatty-acid oxidation and orchestrate macrophage metabolism. Metabolite ceramide leads to reprogramming of macrophages toward immune suppressive TREM2+ tumor associated macrophages, which promote CD8 T cells exhaustion.


Asunto(s)
Neoplasias , Ceramidasa Neutra , Animales , Femenino , Ratones , Linfocitos T CD8-positivos/metabolismo , Ceramidas/metabolismo , Macrófagos/metabolismo , Reprogramación Metabólica , Ceramidasa Neutra/metabolismo , Microambiente Tumoral
15.
J Mater Chem B ; 12(7): 1837-1845, 2024 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-38284228

RESUMEN

Biologically produced nanomaterials capable of therapeutic purposes have received increasing interest in tumor therapy because of their intrinsic biocompatibility. In this study, we made cuttlefish ink (extracted from cuttlefish) and protoporphyrin IX (PpIX) nanoconjugates (CIPs) where PpIX was an endogenous organic compound. In the case of CIPs, PpIX could be triggered by ultrasound (US) for sonodynamic therapy (SDT), and the cuttlefish ink could be excited by a near-infrared laser for photothermal therapy (PTT). Thereafter, tumor growth was greatly inhibited through synergistic SDT-PTT in comparison to single SDT or PTT. In addition, in vivo administration of CIPs showed no noticeable side effects for mouse blood and chief organs, providing an effective strategy for developing biologically produced biomaterials and using them for biotherapy.


Asunto(s)
Neoplasias , Protoporfirinas , Terapia por Ultrasonido , Animales , Ratones , Nanoconjugados , Tinta , Terapia Fototérmica , Terapia Biológica , Neoplasias/terapia
16.
Cancer Lett ; 585: 216667, 2024 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-38280479

RESUMEN

The activation of YAP/TAZ, a pair of paralogs of transcriptional coactivators, initiates a dysregulated transcription program, which is a key feature of human cancer cells. However, it is not fully understood how YAP/TAZ promote dysregulated transcription for tumor progression. In this study, we employed the BioID method to identify the interactome of YAP/TAZ and discovered that YAP/TAZ interact with multiple components of SRCAP complex, a finding that was further validated through endogenous and exogenous co-immunoprecipitation, as well as immunofluorescence experiments. CUT&Tag analysis revealed that SRCAP complex facilitates the deposition of histone variant H2A.Z at target promoters. The depletion of SRCAP complex resulted in a decrease in H2A.Z occupancy and the oncogenic transcription of YAP/TAZ target genes. Additionally, the blockade of SRCAP complex suppressed YAP-driven tumor growth. In a genetically engineered lung adenocarcinoma mouse model and non-small cell lung cancer patients, SRCAP complex and H2A.Z deposition were found to be upregulated. This upregulation was statistically correlated with YAP expression, pathological stages, and poor survival in lung cancer patients. Together, our study uncovers that SRCAP complex plays a critical role in YAP/TAZ oncogenic transcription by coordinating H2A.Z deposition during cancer progression, providing potential targets for cancer diagnosis and prevention.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Animales , Ratones , Humanos , Neoplasias Pulmonares/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Transducción de Señal/genética , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Señalizadoras YAP , Histonas/metabolismo , Fosfoproteínas/genética , Fosfoproteínas/metabolismo , Adenosina Trifosfatasas/metabolismo
17.
Nat Chem Biol ; 20(6): 710-720, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38200110

RESUMEN

Biomolecular condensates have been proposed to mediate cellular signaling transduction. However, the mechanism and functional consequences of signal condensates are not well understood. Here we report that LATS2, the core kinase of the Hippo pathway, responds to F-actin cytoskeleton reduction and forms condensates. The proline-rich motif (PRM) of LATS2 mediates its condensation. LATS2 partitions with the main components of the Hippo pathway to assemble a signalosome for LATS2 activation and for its stability by physically compartmentalizing from E3 ligase FBXL16 complex-dependent degradation, which in turn mediates yes-associated protein (YAP)-transcriptional coactivator with PDZ-binding motif (TAZ) recruitment and inactivation. This oncogenic FBXL16 complex blocks LATS2 condensation by binding to the PRM region to promote its degradation. Disruption of LATS2 condensation leads to tumor progression. Thus, our study uncovers that the signalosomes assembled by LATS2 condensation provide a compartmentalized and reversible platform for Hippo signaling transduction and protein stability, which have potential implications in cancer diagnosis and therapeutics.


Asunto(s)
Vía de Señalización Hippo , Proteínas Serina-Treonina Quinasas , Transducción de Señal , Proteínas Supresoras de Tumor , Proteínas Serina-Treonina Quinasas/metabolismo , Humanos , Proteínas Supresoras de Tumor/metabolismo , Células HEK293 , Animales , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Línea Celular Tumoral , Ratones , Proteínas Señalizadoras YAP/metabolismo , Factores de Transcripción/metabolismo
18.
BMC Pediatr ; 24(1): 5, 2024 01 03.
Artículo en Inglés | MEDLINE | ID: mdl-38172693

RESUMEN

OBJECTIVE: In this study, we aimed to enhance the treatment protocols and help understand the harm caused by the accidental ingestion of magnetic beads by children. METHODS: Data were collected from 72 children with multiple gastrointestinal perforations or gastrointestinal obstructions. The 72 pediatric patients were divided into a perforation and a non-perforation group. The data collected for the analysis included the gender, age, medical history, place of residence (rural or urban), and symptoms along with the educational background of the caregiver, the location and quantity of any foreign bodies discovered during the procedure, whether perforation was confirmed during the procedure, and the number of times magnetic beads had been accidentally ingested. RESULTS: The accuracy rate of preoperative gastrointestinal perforation diagnosis via ultrasound was 71%, while that of the upright abdominal X-ray method was only 46%. In terms of symptoms, the risk of perforation was 13.844 and 12.703 times greater in pediatric patients who experienced vomiting and abdominal pain with vomiting and abdominal distension, respectively, compared to patients in an asymptomatic state. There were no statistical differences between the perforation and the non-perforation groups in terms of age, gender, medical history, and the number of magnetic beads ingested (P > 0.05); however, there were statistical differences in terms of white blood cell count (P = 0.048) and c-reactive protein levels (P = 0.033). A total of 56% of cases underwent a laparotomy along with perforation repair and 19% underwent gastroscopy along with laparotomy. All pediatric patients recovered without complications following surgery. CONCLUSION: Abdominal ultrasonography and/or upright abdominal X-ray analyses should be carried out as soon as possible in case of suspicion of accidental ingestion of magnetic beads by children. In most cases, immediate surgical intervention is required. Given the serious consequences of ingesting this type of foreign body, it is essential to inform parents and/or caregivers about the importance of preventing young children from using such products.


Asunto(s)
Cuerpos Extraños , Tracto Gastrointestinal , Humanos , Niño , Preescolar , Tracto Gastrointestinal/cirugía , Cuerpos Extraños/diagnóstico por imagen , Cuerpos Extraños/cirugía , Cuerpos Extraños/complicaciones , Vómitos/etiología , Ingestión de Alimentos , Fenómenos Magnéticos
19.
J Biotechnol ; 381: 1-10, 2024 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-38176540

RESUMEN

The effects of hydraulic retention time (HRT) on the performance of two-phase anaerobic fermentation for caproic acid production from Chinese cabbage waste (CCW) were investigated. In the electron donor phase, yeast was inoculated to achieve efficient autopoietic ethanol, providing electron donors for the chain elongation process. Shorter HRT led to drastic fluctuations in microorganisms, thus resulting in lower acid yields at HRT of 6 days. At HRT of 10 days, the balanced collaboration of various key bacteria avoided the accumulation of intermediate by-products, and the caproic acid production reached 4660 mg COD/L, which was 119.5% and 154.8% higher than that at HRTs of 6 and 14 days, respectively. At HRT of 14 days, the low ethanol loading rate resulted in ethanol excessive-oxidation to acetic acid. Acetic acid accounted for 41.5% of the total product, while the selectivity of caproic acid was only 15.3%. The main contributor to the production process of caproic acid was Caproiciproducens, while the Ruminalococcaceae also played a role in the process. This study provided a theoretical basis for the efficient production of caproic acid through continuous fermentation with autopoietic electron donors.


Asunto(s)
Reactores Biológicos , Caproatos , Electrones , Fermentación , Reactores Biológicos/microbiología , Anaerobiosis , Ácido Acético , Etanol
20.
World J Pediatr ; 20(2): 165-172, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37676611

RESUMEN

BACKGROUND: Necrotizing enterocolitis (NEC) is the most common severe gastrointestinal emergency in neonates. We designed this study to identify the pathogenic microorganisms of NEC in the microbiota of the small intestine of neonates. METHODS: Using the 16S ribosomal DNA (rDNA) sequencing method, we compared and analyzed the structure and diversity of microbiotas in the intestinal feces of different groups of neonates: patients undergoing jejunostomy to treat NEC (NP group), neonates undergoing jejunostomy to treat other conditions (NN group), and neonates with NEC undergoing conservative treatment (NC group). We took intestinal feces and saliva samples from patients at different time points. RESULTS: The beta diversities of the NP, NN, and NC groups were all similar. When comparing the beta diversities between different time points in the NP group, we found similar beta diversities at time points E1 to E3 but significant differences between the E2-E3 and E4 time points: the abundances of Klebsiella and Enterococcus (Proteobacteria) were higher at the E1-E3 time points; the abundance of Escherichia-Shigella (Proteobacteria) increased at the E2 time point, and the abundance of Klebsiella decreased significantly, whereas that of Streptococcus increased significantly at the E4 time point. CONCLUSIONS: Our results suggest that the pathological changes of intestinal necrosis in the small intestine of infants with NEC are not directly caused by excessive proliferation of pathogenic bacteria in the small intestine. The sources of microbiota in the small intestine of neonates, especially in premature infants, may be affected by multiple factors.


Asunto(s)
Enterocolitis Necrotizante , Enfermedades Fetales , Enfermedades del Recién Nacido , Lactante , Femenino , Recién Nacido , Humanos , ARN Ribosómico 16S/genética , Recien Nacido Prematuro , Intestinos/microbiología , Intestino Delgado
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