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1.
Nat Nanotechnol ; 2024 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-39054386

RESUMEN

Gamma-delta (γδ) T cell-based cancer immunotherapies represent a promising avenue for cancer treatment. However, their development is challenged by the limited expansion and differentiation of the cells ex vivo. Here we induced the endogenous expansion and activation of γδ T cells through oral administration of garlic-derived nanoparticles (GNPs). We found that GNPs could significantly promote the proliferation and activation of endogenous γδ T cells in the intestine, leading to generation of large amount of interferon-γ (IFNγ). Moreover GNP-treated mice showed increased levels of chemokine CXCR3 in intestinal γδ T cells, which can drive their migration from the gut to the tumour environment. The translocation of γδ T cells and IFNγ from the intestine to extraintestinal subcutaneous tumours remodels the tumour immune microenvironment and synergizes with anti-PD-L1, inducing robust antitumour immunity. Our study delineates mechanistic insight into the complex gut-tumour interactome and provides an alternative approach for γδ T cell-based immunotherapy.

2.
Nutr J ; 23(1): 75, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39004744

RESUMEN

OBJECTIVE: An increasing number of studies shown that inadequate energy intake causes an increase in adverse incidents in chronic kidney disease (CKD) patients on low-protein diets (LPD). The study aimed to investigate the relationship between energy intake and cardiovascular mortality in CKD patients on a LPD. METHODS: This was a cross-sectional study, a total of 4264 CKD patients were enrolled from the NHANES database between 2009 and 2018. Restricted cubic spline plots and Cox regression analysis were used to analyze the association between energy intake and cardiovascular mortality in CKD patients on a LPD. Additionally, a nomogram was constructed to estimate cardiovascular survival in CKD patients on a LPD. RESULTS: Among CKD patients on a LPD in the United States, 90.05% had an energy intake of less than 25 kcal/kg/day, compared to 36.94% in CKD patients on a non-LPD. Energy intake and cardiovascular mortality showed a linear relationship in CKD patients on a LPD, while a 'U-shaped' relationship was observed in CKD patients on a non-LPD. Multifactorial Cox regression models revealed that for Per-standard deviation (Per-SD) decrement in energy intake, the risk of cardiovascular mortality increased by 41% (HR: 1.41, 95% CI: 1.12, 1.77; P = 0.004) in CKD patients on a LPD. The concordance index of the nomogram was 0.79 (95% CI, 0.75, 0.83). CONCLUSION: CKD patients, especially those on a LPD, have significantly inadequate energy intake. Lower energy intake is associated with higher cardiovascular mortality in CKD patients on a LPD.


Asunto(s)
Enfermedades Cardiovasculares , Dieta con Restricción de Proteínas , Ingestión de Energía , Encuestas Nutricionales , Insuficiencia Renal Crónica , Humanos , Masculino , Insuficiencia Renal Crónica/mortalidad , Insuficiencia Renal Crónica/complicaciones , Femenino , Enfermedades Cardiovasculares/mortalidad , Persona de Mediana Edad , Estudios Transversales , Encuestas Nutricionales/métodos , Encuestas Nutricionales/estadística & datos numéricos , Dieta con Restricción de Proteínas/métodos , Anciano , Estados Unidos/epidemiología , Adulto , Factores de Riesgo , Modelos de Riesgos Proporcionales
3.
Molecules ; 29(13)2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38998917

RESUMEN

The rapid and sensitive detection of pathogenic and suspicious bioaerosols are essential for public health protection. The impact of pollen on the identification of bacterial species by Raman and Fourier-Transform Infrared (FTIR) spectra cannot be overlooked. The spectral features of the fourteen class samples were preprocessed and extracted by machine learning algorithms to serve as input data for training purposes. The two types of spectral data were classified using classification models. The partial least squares discriminant analysis (PLS-DA) model achieved classification accuracies of 78.57% and 92.85%, respectively. The Raman spectral data were accurately classified by the support vector machine (SVM) algorithm, with a 100% accuracy rate. The two spectra and their fusion data were correctly classified with 100% accuracy by the random forest (RF) algorithm. The spectral processed algorithms investigated provide an efficient method for eliminating the impact of pollen interference.


Asunto(s)
Bacterias , Aprendizaje Automático , Espectrometría Raman , Máquina de Vectores de Soporte , Espectrometría Raman/métodos , Espectroscopía Infrarroja por Transformada de Fourier/métodos , Bacterias/clasificación , Bacterias/aislamiento & purificación , Algoritmos , Polen , Análisis de los Mínimos Cuadrados , Análisis Discriminante
4.
Stem Cell Res Ther ; 15(1): 169, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38886773

RESUMEN

With the development of the economy and the increasing prevalence of skin problems, cutaneous medical aesthetics are gaining more and more attention. Skin disorders like poor wound healing, aging, and pigmentation have an impact not only on appearance but also on patients with physical and psychological issues, and even impose a significant financial burden on families and society. However, due to the complexities of its occurrence, present treatment options cannot produce optimal outcomes, indicating a dire need for new and effective treatments. Mesenchymal stem cells (MSCs) and their secretomics treatment is a new regenerative medicine therapy that promotes and regulates endogenous stem cell populations and/or replenishes cell pools to achieve tissue homeostasis and regeneration. It has demonstrated remarkable advantages in several skin-related in vivo and in vitro investigations, aiding in the improvement of skin conditions and the promotion of skin aesthetics. As a result, this review gives a complete description of recent scientific breakthroughs in MSCs for skin aesthetics and the limitations of their clinical applications, aiming to provide new ideas for future research and clinical transformation.


Asunto(s)
Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Humanos , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/metabolismo , Trasplante de Células Madre Mesenquimatosas/métodos , Piel/citología , Medicina Regenerativa/métodos , Enfermedades de la Piel/terapia , Cicatrización de Heridas , Animales
5.
Animals (Basel) ; 14(9)2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38731280

RESUMEN

Our preliminary research proposed the cytochrome P450 family 7 subfamily A member 1 (CYP7A1) and hydroxyacyl-coenzyme A dehydrogenase trifunctional multienzyme complex beta subunit (HADHB) genes as candidates for association with milk-production traits in dairy cattle because of their differential expression across different lactation stages in the liver tissues of Chinese Holstein cows and their potential roles in lipid metabolism. Hence, we identified single-nucleotide polymorphisms (SNPs) of the CYP7A1 and HADHB genes and validated their genetic effects on milk-production traits in a Chinese Holstein population with the goal of providing valuable genetic markers for genomic selection (GS) in dairy cattle, This study identified five SNPs, 14:g.24676921A>G, 14:g.24676224G>A, 14:g.24675708G>T, 14:g.24665961C>T, and 14:g.24664026A>G, in the CYP7A1 gene and three SNPs, 11:g.73256269T>C, 11:g.73256227A>C, and 11:g.73242290C>T, in HADHB. The single-SNP association analysis revealed significant associations (p value ≤ 0.0461) between the eight SNPs of CYP7A1 and HADHB genes and 305-day milk, fat and protein yields. Additionally, using Haploview 4.2, we found that the five SNPs of CYP7A1 formed two haplotype blocks and that the two SNPs of HADHB formed one haplotype block; notably, all three haplotype blocks were also significantly associated with milk, fat and protein yields (p value ≤ 0.0315). Further prediction of transcription factor binding sites (TFBSs) based on Jaspar software (version 2023) showed that the 14:g.24676921A>G, 14:g.24675708G>T, 11:g.73256269T>C, and 11:g.73256227A>C SNPs could alter the 5' terminal TFBS of the CYP7A1 and HADHB genes. The 14:g.24665961C>T SNP caused changes in the structural stability of the mRNA for the CYP7A1 gene. These alterations have the potential to influence gene expression and, consequently, the phenotype associated with milk-production traits. In summary, we have confirmed the genetic effects of CYP7A1 and HADHB genes on milk-production traits in dairy cattle and identified potential functional mutations that we suggest could be used for GS of dairy cattle and in-depth mechanistic studies of animals.

6.
ACS Omega ; 9(13): 14747-14765, 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38585095

RESUMEN

With the increasing oil demand, more attention has been paid to enhancing oil recovery in old oil fields. CO2 flooding is popular due to its high oil displacement efficiency and ability to reduce greenhouse gas emissions. Laboratory experiments and on-site application cases have shown that the minimum miscibility pressure has a greater impact on CO2 flooding than other factors. If the reservoir pressure is below the minimum miscible pressure, then there is CO2 immiscible flooding. Both theoretical analysis and experimental results show that the recovery rate of CO2 miscible flooding is 2-5 times higher than that of immiscible flooding. If the reservoir pressure is increased by water flooding before CO2 injection, it is easily limited by the physical property parameters. Therefore, accurately determining and effectively reducing the minimum mixing pressure has become the focus of research. Currently, there are two types of methods for determining the minimum miscible pressure: experimental and theoretical methods. The experimental method is generally considered more accurate, including the slim tube test, rising bubble apparatus, and vanishing interfacial tension, etc. However, it is worth noting that the minimum miscibility pressure is dynamically changing, and there will be high economic costs if measured repeatedly through experimental methods during reservoir development. Therefore, it is recognized that the minimum mixing pressure can be determined at any time using theoretical calculation of initial data, which will reduce economic and time costs to a high degree. In this paper, the theoretical calculation method is divided into empirical correlation, state equation, and artificial intelligence algorithm. The techniques for reducing the minimum miscibility pressure can be classified into two categories: miscible solvents and surfactant methods. The miscible solvent method can be further divided into monocomponent and polycomponent methods. This paper compares the advantages and disadvantages of the existing techniques for measuring and reducing MMP and selects the best method.

7.
Front Endocrinol (Lausanne) ; 15: 1369968, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38567310

RESUMEN

Objective: This study aims to investigate the association between lactate dehydrogenase (LDH) and the risk of diabetic kidney disease (DKD) in patients with type 2 diabetes (T2D). Methods: The study enrolled patients with diagnosis of T2D between 2009 and 2018 from the National Nutrition and Health Examination Survey (NHANES) database. Demographic information, laboratory test, and diagnostic data were collected. Restricted cubic spline (RCS) plots were used to assess the dose-effect relationship between LDH levels and the risk of DKD in patients with T2D. Based on LDH levels, individuals were divided into higher and lower groups using dichotomy, and multivariate logistic regression analysis was conducted to explore the relationship between different LDH levels and the risk of DKD in T2D patients. Stratified analysis was performed to assess the consistency of the result. Results: A total of 4888 patients were included in the study, with 2976 (60.9%) patients without DKD and 1912 (39.1%) patients with DKD. RCS plots showed that the risk of DKD increased with increasing LDH levels. Multifactorial logistic regression analysis revealed that T2D patients with higher LDH levels had a 45% increased risk of DKD compared to those with lower LDH levels (OR=1.45; 95% CI: 1.11-1.89). Furthermore, each standard deviation increase in LDH level was associated with a 24% increase in DKD incidence among T2D patients (OR=1.24; 95% CI: 1.07-1.44). Stratified analysis consistently supported these findings. Conclusions: LDH can serve as a valuable biomarker for screening DKD in patients with T2D.


Asunto(s)
Diabetes Mellitus Tipo 2 , Nefropatías Diabéticas , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Nefropatías Diabéticas/diagnóstico , Nefropatías Diabéticas/epidemiología , Nefropatías Diabéticas/etiología , Factores de Riesgo , Encuestas Nutricionales , L-Lactato Deshidrogenasa
8.
Sci Adv ; 9(42): eadi0699, 2023 10 20.
Artículo en Inglés | MEDLINE | ID: mdl-37851811

RESUMEN

Neurological disorders are a common feature in patients who recover from severe acute pneumonia. However, the underlying mechanisms remain poorly understood. Here, we show that the neurological syndromes after severe acute pneumonia are partly attributed to the translocation of endogenous bacteria from the lung to the brain during pneumonia. Using principal components analysis, similarities were found between the brain's flora species and those of the lungs, indicating that the bacteria detected in the brain may originate from the lungs. We also observed impairment of both the lung-blood and brain-blood barriers, allowing endogenous lung bacteria to invade the brain during pneumonia. An elevated microglia and astrocyte activation signature via bacterial infection-related pathways was observed, indicating a bacterial-induced disruption of brain homeostasis. Collectively, we identify endogenous lung bacteria that play a role in altering brain homeostasis, which provides insight into the mechanism of neurological syndromes after severe pneumonia.


Asunto(s)
Bacterias , Encéfalo , Pulmón , Enfermedades del Sistema Nervioso , Neumonía , Humanos , Encéfalo/microbiología , Pulmón/microbiología , Enfermedades del Sistema Nervioso/complicaciones , Neumonía/etiología
9.
Plants (Basel) ; 12(20)2023 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-37896088

RESUMEN

The NAC (NAM, ATAF1/2 and CUC2) gene family is one of the largest plant-specific transcription factor families, functioning as crucial regulators in diverse biological processes such as plant growth and development as well as biotic and abiotic stress responses. Although it has been widely characterized in many plants, the significance of the NAC family in Dendrobium officinale remained elusive up to now. In this study, a genome-wide search method was conducted to identify NAC genes in Dendrobium officinale (DoNACs) and a total of 110 putative DoNACs were obtained. Phylogenetic analysis classified them into 15 subfamilies according to the nomenclature in Arabidopsis and rice. The members in the subfamilies shared more similar gene structures and conversed protein domain compositions. Furthermore, the expression profiles of these DoNACs were investigated in diverse tissues and under cold stress by RNA-seq data. Then, a total of five up-regulated and five down-regulated, cold-responsive DoNACs were validated through QRT-PCR analysis, demonstrating they were involved in regulating cold stress response. Additionally, the subcellular localization of two down-regulated candidates (DoNAC39 and DoNAC58) was demonstrated to be localized in the nuclei. This study reported the genomic organization, protein domain compositions and expression patterns of the NAC family in Dendrobium officinale, which provided targets for further functional studies of DoNACs and also contributed to the dissection of the role of NAC in regulating cold tolerance in Dendrobium officinale.

10.
Cell Rep ; 42(10): 113138, 2023 10 31.
Artículo en Inglés | MEDLINE | ID: mdl-37738123

RESUMEN

Advances in the development of therapeutic extracellular vesicles (EVs) for cancer immunotherapy have allowed them to emerge as an alternative to cell therapy. In this proof-of-concept work, we develop bispecific EVs (BsEVs) by genetically engineering EV-producing dendritic cells (DCs) with aCD19 scFv and PD1 for targeting tumor antigens and blocking immune checkpoint proteins simultaneously. We find that these bispecific EVs (EVs-PD1-aCD19) have an impressive ability to accumulate in huCD19-expressing solid tumors following intravenous injection. In addition, EVs-PD1-aCD19 can remarkably reverse the immune landscape of the solid tumor by blocking PD-L1. Furthermore, EVs-PD1-aCD19 can also target tumor-derived EVs in circulation, which prevents the formation of a premetastatic niche in other tissues. Our technology is a demonstration of bispecific EV-based cancer immunotherapy, which may inspire treatments against various types of tumors with different surface antigens and even a patient-tailored therapy.


Asunto(s)
Vesículas Extracelulares , Neoplasias , Humanos , Vesículas Extracelulares/metabolismo , Neoplasias/terapia , Neoplasias/metabolismo , Antígenos de Neoplasias/metabolismo , Inmunoterapia , Células Dendríticas
11.
J Radiat Res ; 64(6): 880-892, 2023 Nov 21.
Artículo en Inglés | MEDLINE | ID: mdl-37697698

RESUMEN

On the basis of the previous research, the Traditional Chinese Medicine theory was used to improve the drug composition for gastrointestinal acute radiation syndrome (GI-ARS). The purpose of this study was to study the therapeutic mechanism of Liangxue-Guyuan-Yishen decoction (LGYD) on GI-ARS and to provide a new scheme for the treatment of radiation injury. Here, we investigated the effects of LGYD on intestinal stem cells (ISCs) in a GI-ARS rat model. Rat health and survival and the protective efficacy of LGYD on the intestines were analyzed. The active principles in LGYD were detected using liquid chromatography-mass spectrometry (LC-MS). ISC proliferation, intestinal epithelial tight junction (TJ) protein expression and regulatory pathways were explored using immunohistochemistry, western blotting (WB) and reverse transcription quantitative polymerase chain reaction (RT-qPCR), respectively. Involvement of the WNT and MEK/ERK pathways in intestinal recovery was screened using network pharmacology analysis and validated by WB and RT-qPCR. LGYD administration significantly improved health and survival in GI-ARS rats. Pathological analysis showed that LGYD ameliorated radiation-induced intestinal injury and significantly promoted LGR5+ stem cell regeneration in the intestinal crypts, upregulated TJ protein, and accelerated crypt reconstruction in the irradiated rats. LC-MS revealed ≥13 constituents that might contribute to LGYD's protective effects. Collectively, LGYD can promote crypt cell proliferation and ISCs after radiation damage, the above effect may be related to WNT and MEK/ERK pathway.


Asunto(s)
Síndrome de Radiación Aguda , Ratas , Animales , Síndrome de Radiación Aguda/tratamiento farmacológico , Intestinos/patología , Células Madre/metabolismo , Quinasas de Proteína Quinasa Activadas por Mitógenos/metabolismo , Quinasas de Proteína Quinasa Activadas por Mitógenos/farmacología , Mucosa Intestinal
12.
Mol Pharm ; 20(9): 4743-4757, 2023 09 04.
Artículo en Inglés | MEDLINE | ID: mdl-37579048

RESUMEN

Currently, the low survival rate and poor prognosis of patients with nasopharyngeal carcinoma are ascribed to the lack of early and accurate diagnosis and resistance to radiotherapy. In parallel, the integration of imaging-guided diagnosis and precise treatment has gained much attention in the field of theranostic nanotechnology. However, constructing dual-modal imaging-guided nanotheranostics with desired imaging performance as well as great biocompatibility remains challenging. Therefore, we developed a simple but multifunctional nanotheranostic GdCPP for the early and accurate diagnosis and efficient treatment of nasopharyngeal carcinoma (NPC), which combined fluorescence imaging and magnetic resonance imaging (MRI) onto a single nanoplatform for imaging-guided subsequent photodynamic therapy (PDT). GdCPP had an appropriate particle size (81.93 ± 0.69 nm) and was highly stable, resulting in sufficient tumor accumulation, which along with massive reactive oxygen species (ROS) generation upon irradiation further significantly killed tumor cells. Moreover, GdCPP owned much stronger r1 relaxivity (9.396 mM-1 s-1) compared to clinically used Gd-DTPA (5.034 mM-1 s-1) and exhibited better T1WI MRI performance. Under dual-modal imaging-guided PDT, GdCPP achieved efficient therapeutic outcomes without causing any noticeable tissue damage. The results of in vitro and in vivo studies indicated that GdCPP may be a suitable candidate for dual-modal imaging-guided precision tumor therapy.


Asunto(s)
Nanopartículas , Neoplasias Nasofaríngeas , Fotoquimioterapia , Humanos , Fotoquimioterapia/métodos , Nanomedicina Teranóstica/métodos , Carcinoma Nasofaríngeo/diagnóstico por imagen , Carcinoma Nasofaríngeo/tratamiento farmacológico , Imagen por Resonancia Magnética/métodos , Neoplasias Nasofaríngeas/diagnóstico por imagen , Neoplasias Nasofaríngeas/tratamiento farmacológico , Línea Celular Tumoral
13.
Aging (Albany NY) ; 15(14): 7084-7097, 2023 07 24.
Artículo en Inglés | MEDLINE | ID: mdl-37490715

RESUMEN

Severe pneumonia may induce sequelae and accelerated aging process even after the person has recovered. However, the underline mechanism is not very clear. More research is needed to fully understand the long-term effects of severe pneumonia. In this study, we found that mice recovered from severe pneumonia showed lung immunosenescence, which was characterized by a bias naive-memory balance of T lymphocytes in the lung. The reduction of naïve T cells is associated with the diminished immune response to cancer or external new antigens, which is one of the key changes that occurs with age. Our results also indicate the link between severe pneumonia and aging process, which is mediated by the disrupted T cells homeostasis in the lungs after pneumonia.


Asunto(s)
Inmunosenescencia , Neumonía , Animales , Ratones , Linfocitos T CD8-positivos , Progresión de la Enfermedad , Pulmón , Envejecimiento
14.
Ann Surg Oncol ; 30(9): 5912-5922, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37389655

RESUMEN

BACKGROUND: Small pulmonary nodules (<3 cm) can sometimes be unrecognizable and nonpalpable in video-assisted thoracoscopic surgery (VATS). Near-infrared fluorescence (NIF) VATS after indocyanine green (ICG) inhalation may effectively guide surgeons to locate the nodules. OBJECTIVE: This study aimed to investigate the safety, feasibility, and efficacy of ICG inhalation-based NIF imaging for guiding small pulmonary nodule resections. METHODS: Between February and May 2021, the first-stage, non-randomized trial enrolled 21 patients with different nodule depth, ICG inhalation doses, post-inhalation surgery times, and nodule types at a tertiary referral hospital. Between May 2021 and May 2022, the second-stage randomized trial enrolled 56 patients, who were randomly assigned to the fluorescence VATS (FLVATS) or the white-light VATS (WLVATS) group. The ratio of effective guidance and the time consumption for nodule localization were compared. RESULTS: The first-stage trial proved this new method is safe and feasible, and established a standardized protocol with optimized nodule depth (≤1 cm), ICG dose (0.20-0.25 mg/kg), and surgery window (50-90 min after ICG inhalation). In the second-stage trial, the FLVATS achieved 87.1% helpful nodule localization guidance, which was significantly higher than the WLVATS (59.1%, p < 0.05). The mean nodule locating time (standard deviation) was 1.8 [0.9] and 3.3 [2.3] min, respectively. Surgeons adopting FLVATS were significantly faster (p < 0.01), especially when locating small ground-glass opacities (1.3 [0.6] min vs. 7.0 [3.5] min, p < 0.05). Five of 31 nodules (16.1%) were only detectable by FLVATS, whereas both white light and palpation failed. CONCLUSIONS: This new method is safe and feasible for small pulmonary nodule resection. It significantly improves nodule localization rates with less time consumption, and hence is highly worthy for clinical promotion. Clinical Trial Registration Chinese Clinical Trial Registry Identifier: ChiCTR2100047326.


Asunto(s)
Neoplasias Pulmonares , Nódulos Pulmonares Múltiples , Nódulo Pulmonar Solitario , Humanos , Verde de Indocianina , Cirugía Torácica Asistida por Video/métodos , Neoplasias Pulmonares/cirugía , Tomografía Computarizada por Rayos X/métodos , Pulmón , Nódulos Pulmonares Múltiples/diagnóstico por imagen , Nódulos Pulmonares Múltiples/cirugía , Nódulo Pulmonar Solitario/diagnóstico por imagen , Nódulo Pulmonar Solitario/cirugía
15.
Cell Rep ; 42(4): 112346, 2023 04 25.
Artículo en Inglés | MEDLINE | ID: mdl-37022934

RESUMEN

Nanoplastics (NPs) as contaminants in food and water have drawn increasing public attention. However, little is known about how NPs shape the gut immune landscape after injection. In this study, we fabricate NPs (∼500 nm) and microplastics (MPs) (∼2 µm) and evaluate their in vivo effects by feeding them to mice. The results suggest that NPs show a better ability to induce gut macrophage activation than MPs. In addition, NPs trigger gut interleukin-1 (IL-1)-producing macrophage reprogramming via inducing lysosomal damage. More importantly, IL-1 signaling from the intestine can affect brain immunity, leading to microglial activation and Th17 differentiation, all of which correlates with a decline in cognitive and short-term memory in NP-fed mice. Thus, this study provides insight into the mechanism of action of the gut-brain axis, delineates the way NPs reduce brain function, and highlights the importance of fixing the plastic pollution problem worldwide.


Asunto(s)
Interleucina-1 , Microplásticos , Animales , Ratones , Microplásticos/toxicidad , Plásticos , Macrófagos , Encéfalo , Intestinos
16.
Nano Lett ; 23(8): 3516-3523, 2023 04 26.
Artículo en Inglés | MEDLINE | ID: mdl-37043775

RESUMEN

The impact of nanoplastics (NPs) on human health is still not well understood, and more research is needed to better understand the risks associated with these particles. In this study, we found that oral administration of polyethylene (PE) NPs in a mice model significantly disrupted the intestinal microenvironment, which shapes adaptive immune response and favors the established in situ colorectal tumor growth. Using single-cell RNA sequencing technology, we show that NPs triggered colon IL-1ß-producing macrophages by inducing lysosome damage, leading to colonic Treg and Th17 differentiation associated with T cell exhaustion, which creates a colon environment that favors the tumor initiation and progress. A similar effect is also observed in polystyrene NPs. Our result provides insight into the potential link between NPs ingestion and colon tumorigenesis, and the urgency of addressing plastic pollution worldwide.


Asunto(s)
Colon , Microplásticos , Humanos , Animales , Ratones , Intestinos , Inmunidad Adaptativa , Macrófagos , Poliestirenos
17.
ACS Nano ; 17(1): 760-774, 2023 01 10.
Artículo en Inglés | MEDLINE | ID: mdl-36520665

RESUMEN

Tumor vaccines have been showing a relatively weak response rate in cancer patients, while deficiencies in delivery efficiency to dendritic cells (DCs), as well as DC-intrinsic immunosuppressive signals, contribute to a great extent. In this work, we report an implantable blood clot loaded with liposomes-protamine-hyaluronic acid nanoparticles (LPH NPs) containing vaccine (LPH-vaccine) and LPH NPs containing siRNA (LPH-siRNA) for synergistic DC recruitment and activation. The subcutaneously implanted blood clot scaffold can recruit abundant immune cells, particularly DCs, to form a DC-rich environment in vivo. Within the scaffold, LPH-vaccine effectively delivers antigens and adjuvants to the recruited DCs and induces the maturation of DCs. More importantly, LPH-siRNA that targets programmed death-ligand 1 (PD-L1) and T cell immunoglobulin and mucin-containing molecule 3 (TIM-3) can reduce immunosuppressive signals in mature DCs and prevent the DCs from expressing a regulatory program in the scaffold. The activated DCs correlate with an improved magnitude and efficacy of T cell priming, resulting in the production of tumor antigen-specific T cells in multiple mouse models. Our strategy can also be used for patient-tailored therapy by change of tumor neoantigens, suggesting a promising strategy for cancer therapy in the clinic.


Asunto(s)
Vacunas contra el Cáncer , Neoplasias , Trombosis , Animales , Ratones , ARN Interferente Pequeño/genética , Liposomas , Antígeno B7-H1/genética , Receptor 2 Celular del Virus de la Hepatitis A , Inmunoterapia/métodos , Neoplasias/terapia , Células Dendríticas
18.
Ann Thorac Surg ; 115(3): e79-e81, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-35364050

RESUMEN

We report a clinical case of using indocyanine green inhalation to achieve intraoperative near-infrared fluorescence visualization of pulmonary ground-glass opacity in thoracoscopic wedge resection. The patient underwent thoracoscopic wedge resection under the real-time navigation of a near-infrared fluorescence imaging system with the indocyanine green inhalation performed 85 minutes before the surgery. The nebulized inhalation of indocyanine green (dose of 0.25 mg/kg) successfully guided surgeons to localize the small ground-glass opacity due to a filling defect of the fluorescence. The thoracoscopic near-infrared fluorescence navigation system delineated the tumor margin with high contrast and helped to minimize the damage to lung function.


Asunto(s)
Verde de Indocianina , Neoplasias Pulmonares , Humanos , Fluorescencia , Toracoscopía/métodos , Pulmón/cirugía , Neoplasias Pulmonares/cirugía
19.
Cancer Sci ; 114(4): 1596-1605, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36541519

RESUMEN

To achieve a better treatment regimen and follow-up assessment design for intensity-modulated radiotherapy (IMRT)-treated nasopharyngeal carcinoma (NPC) patients, an accurate progression-free survival (PFS) time prediction algorithm is needed. We propose developing a PFS prediction model of NPC patients after IMRT treatment using a deep learning method and comparing that with the traditional texture analysis method. One hundred and fifty-one NPC patients were included in this retrospective study. T1-weighted, proton density and dynamic contrast-enhanced magnetic resonance (MR) images were acquired. The expression level of five genes (HIF-1α, EGFR, PTEN, Ki-67, and VEGF) and infection of Epstein-Barr (EB) virus were tested. A residual network was trained to predict PFS from MR images. The output as well as patient characteristics were combined using a linear regression model to provide a final PFS prediction. The prediction accuracy was compared with that of the traditional texture analysis method. A regression model combining the deep learning output with HIF-1α expression and Epstein-Barr infection provides the best PFS prediction accuracy (Spearman correlation R2  = 0.53; Harrell's C-index = 0.82; receiver operative curve [ROC] analysis area under the curve [AUC] = 0.88; log-rank test hazard ratio [HR] = 8.45), higher than a regression model combining texture analysis with HIF-1α expression (Spearman correlation R2  = 0.14; Harrell's C-index =0.68; ROC analysis AUC = 0.76; log-rank test HR = 2.85). The deep learning method does not require a manually drawn tumor region of interest. MR image processing using deep learning combined with patient characteristics can provide accurate PFS prediction for nasopharyngeal carcinoma patients and does not rely on specific kernels or tumor regions of interest, which is needed for the texture analysis method.


Asunto(s)
Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/patología , Neoplasias Nasofaríngeas/diagnóstico por imagen , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/radioterapia , Estudios Retrospectivos , Tasa de Supervivencia , Pronóstico , Imagen por Resonancia Magnética/métodos , Herpesvirus Humano 4/genética , Redes Neurales de la Computación , Expresión Génica
20.
Ann Transl Med ; 10(20): 1102, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36388818

RESUMEN

Background: Childhood hand function is considered to be one of the strongest predictors of the ability to participate in daily activities as children with cerebral palsy (CP) reach adulthood. The manual ability classification system (MACS) is currently the most widely used for grading hand function in children with CP. However, the MACS method is subjective and may be affected by the raters' experience. Hand knob is an important control center for hand movement. Therefor this study aimed to develop and validate an objective model for hand function estimation in children with CP and visualize it as a nomogram. Methods: A total of 70 Children (2-12 years old) with CP underwent magnetic resonance imaging (MRI) scanning, MACS assessment. According to MACS, children with CP were divided into mild impairment group (grade I-III) and severe impairment group (grade IV-V). Hand function prediction models based on (I) hand knob score, (II) clinical features, and (III) the combination of clinical features and hand knob score were developed and validated separately. The models were subjected to stepwise regression according to the maximum likelihood method, and the Akaike information criterion was used to select the best model. Model discrimination was assessed using receiver operating characteristic (ROC) and calibration curves. The nomogram was finally built according to the best model. Results: The area under the curve (AUC) of the hand knob score model in the training set was 0.752, the clinical features model was 0.819, and the hand knob score and clinical features combined model was 0.880. The AUC of the hand knob score model in the validation set was 0.765, the clinical features model was 0.782, and the combined model was 0.894. The best model was the hand knob score-clinical features combined model, and the nomogram finally incorporated two assessment items: the hand knob score and white matter injury. The estimated probability of hand function injury degree of the combined model displayed good agreement with the actual occurrence probability. Conclusions: The hand knob score-clinical features combined model can be used to preliminarily assess the degree of hand impairment in children with CP, with good calibration.

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