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1.
J Cell Mol Med ; 28(16): e70014, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39153211

RESUMEN

Anaplastic thyroid cancer (ATC), an aggressive malignancy with virtually 100% disease-specific mortality, has long posed a formidable challenge in oncology due to its resistance to conventional treatments and the severe side effects associated with current regimens such as doxorubicin chemotherapy. Consequently, there was urgent need to identify novel candidate compounds that could provide innovative therapeutic strategies for ATC. Ophiopogonin D' (OPD'), a triterpenoid saponin extracted, yet its roles in ATC has not been reported. Our data demonstrated that OPD' potently inhibited proliferation and metastasis of ATC cells, promoting cell cycle arrest and apoptosis. Remarkably, OPD' impeded growth and metastasis of ATC in vitro and in vivo, displaying an encouraging safety profile. Regulator of G-protein signalling 4 (RGS4) expression was significantly up-regulated in ATC compared to normal tissues, and this upregulation was suppressed by OPD' treatment. Mechanistically, we elucidated that the transcription factor JUN bound to the RGS4 promoter, driving its transactivation. However, OPD' interacted with JUN, attenuating its transcriptional activity and thereby disrupting RGS4 overexpression. In summary, our research revealed that OPD' bound with JUN, which in turn resulted in the suppression of transcriptional activation of RGS4, thereby eliciting cell cycle arrest and apoptosis in ATC cells. These findings could offer promise in the development of high-quality candidate compounds for treatment in ATC.


Asunto(s)
Apoptosis , Proliferación Celular , Proteínas RGS , Saponinas , Transducción de Señal , Espirostanos , Carcinoma Anaplásico de Tiroides , Humanos , Carcinoma Anaplásico de Tiroides/tratamiento farmacológico , Carcinoma Anaplásico de Tiroides/metabolismo , Carcinoma Anaplásico de Tiroides/patología , Saponinas/farmacología , Proteínas RGS/metabolismo , Proteínas RGS/genética , Proliferación Celular/efectos de los fármacos , Animales , Línea Celular Tumoral , Transducción de Señal/efectos de los fármacos , Apoptosis/efectos de los fármacos , Espirostanos/farmacología , Ratones , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Puntos de Control del Ciclo Celular/efectos de los fármacos , Proteínas Proto-Oncogénicas c-jun/metabolismo , Ratones Desnudos , Neoplasias de la Tiroides/tratamiento farmacológico , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/metabolismo , Neoplasias de la Tiroides/genética , Ensayos Antitumor por Modelo de Xenoinjerto , Metástasis de la Neoplasia
2.
Foods ; 13(13)2024 Jun 29.
Artículo en Inglés | MEDLINE | ID: mdl-38998575

RESUMEN

In this study, three different brands of commercially available marinated tofu were analyzed and compared with homemade products to explore the effect of key flavor substances on their sensory quality, sensory properties, texture characteristics, and volatile components. The texture characteristics and flavor substances of the three brands of commercially available marinated tofu were significantly different from those of homemade products. A total of 64 volatile components were identified by headspace-gas chromatography-ion mobility spectrometry (HS-GC-IMS), mainly including 11 hydrocarbons, 11 alcohols, 10 ketones, 15 aldehydes, 4 esters, 1 acid, and 12 other volatile substances. Among these, nine key flavor compounds (ROAV > 1, VIP > 1) were identified using the relative odor activity value (ROAV) combined with a partial least squares discriminant analysis (PLS-DA) and variable importance in projection, including α-Pinene, ß-Myrcene, α-Phellandrene, 1-Penten-3-one, Butanal, 3-Methyl butanal, acetic acid ethyl ester, 1,8-Cineol, and 2-Pentyl furan. The correlation heatmap showed that sensory evaluation was positively correlated with hardness, gumminess, chewiness, and springiness while negatively correlated with 2-Pentyl furan, α-Pinene, resilience, α-Phellandrene, 1-Penten-3-one, acetic acid ethyl ester, and 1,8-Cineol. Overall, this study provides a theoretical reference for developing new instant marinated tofu snacks.

3.
J Chem Inf Model ; 64(15): 5931-5943, 2024 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-39042485

RESUMEN

Vast published dielectric ceramics literature is a natural database for big-data analysis, discovering structure-property relationships, and property prediction. We constructed a data-mining pipeline based on natural language processing (NLP) to extract property information from about 12,900 published dielectric ceramics articles and normalized more than 20 properties. The micro-F1 scores for sentence classification, named entities recognition, relation extraction (related), and relation extraction (same), are 91.6, 82.4, 91.4, and 88.3%, respectively. We demonstrated the distribution of some essential properties according to the publication years to reveal the tendency. In order to test the reliability of the data extraction, we trained an XGBoost model to predict the dielectric constant and used the SHAP module to interpret the contribution of each feature in order to identify some of the factors that determine the dielectric properties. The result shows that including Q × f in the model can increase the dielectric constant prediction accuracy. Our work can give some hints to experimentalists on their way to improve the performances of cutting-edge materials.


Asunto(s)
Cerámica , Minería de Datos , Minería de Datos/métodos , Cerámica/química , Procesamiento de Lenguaje Natural , Bases de Datos Factuales
4.
Cancer Immunol Immunother ; 73(8): 150, 2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38832948

RESUMEN

Hotspot driver mutations presented by human leukocyte antigens might be recognized by anti-tumor T cells. Based on their advantages of tumor-specificity and immunogenicity, neoantigens derived from hotspot mutations, such as PIK3CAH1047L, may serve as emerging targets for cancer immunotherapies. NetMHCpan V4.1 was utilized for predicting neoepitopes of PIK3CA hotspot mutation. Using in vitro stimulation, antigen-specific T cells targeting the HLA-A*11:01-restricted PIK3CA mutation were isolated from healthy donor-derived peripheral blood mononuclear cells. T cell receptors (TCRs) were cloned using single-cell PCR and sequencing. Their functionality was assessed through T cell activation markers, cytokine production and cytotoxic response to cancer cell lines pulsed with peptides or transduced genes of mutant PIK3CA. Immunogenic mutant antigens from PIK3CA and their corresponding CD8+ T cells were identified. These PIK3CA mutation-specific CD8+ T cells were subsequently enriched, and their TCRs were isolated. The TCR clones exhibited mutation-specific and HLA-restricted reactivity, demonstrating varying degrees of functional avidity. Identified TCR genes were transferred into CD8+ Jurkat cells and primary T cells deficient of endogenous TCRs. TCR-expressing cells demonstrated specific recognition and reactivity against the PIK3CAH1047L peptide presented by HLA-A*11:01-expressing K562 cells. Furthermore, mutation-specific TCR-T cells demonstrated an elevation in cytokine production and profound cytotoxic effects against HLA-A*11:01+ malignant cell lines harboring PIK3CAH1047L. Our data demonstrate the immunogenicity of an HLA-A*11:01-restricted PIK3CA hotspot mutation and its targeting therapeutic potential, together with promising candidates of TCR-T cell therapy.


Asunto(s)
Fosfatidilinositol 3-Quinasa Clase I , Mutación , Neoplasias , Receptores de Antígenos de Linfocitos T , Humanos , Fosfatidilinositol 3-Quinasa Clase I/genética , Fosfatidilinositol 3-Quinasa Clase I/inmunología , Receptores de Antígenos de Linfocitos T/inmunología , Receptores de Antígenos de Linfocitos T/genética , Neoplasias/inmunología , Neoplasias/terapia , Neoplasias/genética , Inmunoterapia/métodos , Antígeno HLA-A11/genética , Antígeno HLA-A11/inmunología , Linfocitos T CD8-positivos/inmunología , Epítopos de Linfocito T/inmunología , Epítopos de Linfocito T/genética , Antígenos de Neoplasias/inmunología , Antígenos de Neoplasias/genética , Línea Celular Tumoral
5.
Cancer Immunol Res ; 2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38900485

RESUMEN

Endoplasmic reticulum (ER) stress leads to hepatocellular carcinoma (HCC) progression. Small extracellular vesicles (sEVs) play a crucial role in modulating the tumor microenvironment (TME) by influencing cellular communication and immune responses. However, it is unclear whether ER stress modulates the TME through sEVs. In the current study, we investigated the effects and underlying mechanisms of ER stress on the HCC TME. In vivo and in vitro experiments showed that overactivated ER stress was a salient attribute of the immunosuppressive HCC TME. This was caused by the ATF4-promoted release of SNHG6-carrying sEVs, which attenuated T cell-mediated immune responses. Overall, SNHG6 modulated the immunosuppressive TME and aggravated ER stress. Meanwhile, targeting SNHG6 facilitated M1-like macrophage and CD8+ T-cell infiltration and decreased the proportion of M2-like macrophages. In addition, SNHG6 knockdown enhanced anti-PD-1 immunotherapeutic efficacy. Moreover, in HCC patients, overexpression of SNHG6 was associated with a lack of response to anti-PD-1 therapy and poor prognosis, whereas low SNHG6 expression was associated with improved therapeutic efficacy and prognoses. These data indicate that a correlation exists among ER stress, sEVs, an immunosuppressive HCC TME, and immunotherapeutic efficacy. Hence, SNHG6-targeted therapy may represent an effective strategy for patients with HCC.

6.
Int J Biol Macromol ; 273(Pt 1): 132926, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38851610

RESUMEN

In recent years, the development of environmentally friendly packaging materials using biodegradable polymers has emerged as a key challenge for scientists and consumers in response to resource depletion and environmental issues caused by plastic packaging materials. Starch and polyvinyl alcohol (PVA) are being recognized as excellent candidates for producing biodegradable food packaging films. Polymer blending has emerged as a practical approach to overcome the limitations of biopolymer films by developing films with unique properties and enhancing overall performance. This review briefly introduces the molecular structure and properties of starch and PVA, summarizes the common preparation methods and properties of starch/PVA blend films, and focuses on different strategies used to enhance starch/PVA blend films, including nanoparticles, plant extracts, and cross-linking agents. Additionally, this study summarizes the application of starch/PVA blend films as active and smart packaging in food preservation systems. This study demonstrates that starch and PVA blends have potential in manufacturing biodegradable food films with excellent properties due to their excellent compatibility and intermolecular interactions, and can be used as packaging films for a variety of foods to extend their shelf life.


Asunto(s)
Embalaje de Alimentos , Alcohol Polivinílico , Almidón , Alcohol Polivinílico/química , Embalaje de Alimentos/métodos , Almidón/química , Plásticos/química
7.
Carbohydr Polym ; 339: 122228, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-38823903

RESUMEN

Meat products consumption is rising globally, but concerns about sustainability, fat content, and shelf life. Synthetic additives and preservatives used for extending the shelf life of meat often carry health and environmental drawbacks. Seed mucilage, natural polysaccharides, possesses unique functional properties like water holding, emulsifying, and film forming, offering potential alternatives in meat processing and preservation. This study explores the application of seed mucilage from diverse sources (e.g., flaxseed, psyllium, basil) in various meat and meat products processing and preservation. Mucilage's water-holding and emulsifying properties can potentially bind fat and decrease the overall lipid content in meat and meat-based products. Moreover, antimicrobial and film-forming properties of mucilage can potentially inhibit microbial growth and reduce oxidation, extending the shelf life. This review emphasizes the advantages of incorporating mucilage into processing and coating strategies for meat and seafood products.


Asunto(s)
Conservación de Alimentos , Productos de la Carne , Mucílago de Planta , Semillas , Semillas/química , Productos de la Carne/análisis , Mucílago de Planta/química , Conservación de Alimentos/métodos , Lino/química , Biopolímeros/química , Polisacáridos/química , Animales , Psyllium/química , Manipulación de Alimentos/métodos
8.
Gut Microbes ; 16(1): 2341717, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38717360

RESUMEN

The occurrence and progression of tumors are often accompanied by disruptions in the gut microbiota. Inversely, the impact of the gut microbiota on the initiation and progression of cancer is becoming increasingly evident, influencing the tumor microenvironment (TME) for both local and distant tumors. Moreover, it is even suggested to play a significant role in the process of tumor immunotherapy, contributing to high specificity in therapeutic outcomes and long-term effectiveness across various cancer types. Probiotics, with their generally positive influence on the gut microbiota, may serve as effective agents in synergizing cancer immunotherapy. They play a crucial role in activating the immune system to inhibit tumor growth. In summary, this comprehensive review aims to provide valuable insights into the dynamic interactions between probiotics, gut microbiota, and cancer. Furthermore, we highlight recent advances and mechanisms in using probiotics to improve the effectiveness of cancer immunotherapy. By understanding these complex relationships, we may unlock innovative approaches for cancer diagnosis and treatment while optimizing the effects of immunotherapy.


Asunto(s)
Microbioma Gastrointestinal , Inmunoterapia , Neoplasias , Probióticos , Microambiente Tumoral , Probióticos/uso terapéutico , Probióticos/administración & dosificación , Probióticos/farmacología , Humanos , Inmunoterapia/métodos , Neoplasias/terapia , Neoplasias/inmunología , Neoplasias/microbiología , Microambiente Tumoral/inmunología , Animales
9.
Food Res Int ; 187: 114390, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38763652

RESUMEN

In light of the commendable advantages inherent in natural polymers such as biocompatibility, biodegradability, and cost-effectiveness, researchers are actively engaged in the development of biopolymer-based biodegradable food packaging films (BFPF). However, a notable limitation is that most biopolymers lack intrinsic antimicrobial activity, thereby restricting their efficacy in food preservation. To address this challenge, various active substances with antibacterial properties have been explored as additives to BFPF. Among these, ε-polylysine has garnered significant attention in BFPF applications owing to its outstanding antibacterial properties. This study provides a brief overview of the synthesis method and chemical properties of ε-polylysine, and comprehensively examines its impact as an additive on the properties of BFPF derived from diverse biopolymers, including polysaccharides, proteins, aliphatic polyesters, etc. Furthermore, the practical applications of various BFPF functionalized with ε-polylysine in different food preservation scenarios are summarized. The findings underscore that ε-polylysine, functioning as an antibacterial agent, not only directly enhances the antimicrobial activity of BFPF but also serves as a cross-linking agent, interacting with biopolymer molecules to influence the physical and mechanical properties of BFPF, thereby enhancing their efficacy in food preservation.


Asunto(s)
Antibacterianos , Embalaje de Alimentos , Conservación de Alimentos , Polilisina , Polilisina/química , Embalaje de Alimentos/métodos , Biopolímeros/química , Conservación de Alimentos/métodos , Antibacterianos/farmacología , Antibacterianos/química , Películas Comestibles
10.
Chem Sci ; 15(18): 6690-6706, 2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38725502

RESUMEN

The field of metal-organic frameworks (MOFs) includes a vast number of hybrid organic and inorganic porous materials with wide-ranging applications. In particular, the Cu(i) ion exhibits rich coordination chemistry in MOFs and can exist in two-, three-, and four-coordinate environments, which gives rise to many structural motifs and potential applications. Direct characterization of the structurally and chemically important Cu(i) local environments is essential for understanding the sources of specific MOF properties. For the first time, 63/65Cu solid-state NMR has been used to investigate a variety of Cu(i) sites and local coordination geometries in Cu MOFs. This approach is a sensitive probe of the local Cu environment, particularly when combined with density functional theory calculations. A wide range of structurally-dependent 63/65Cu NMR parameters have been observed, including 65Cu quadrupolar coupling constants ranging from 18.8 to 74.8 MHz. Using the data from this and prior studies, a correlation between Cu quadrupolar coupling constants, Cu coordination number, and local Cu coordination geometry has been established. Links between DFT-calculated and experimental Cu NMR parameters are also presented. Several case studies illustrate the feasibility of 63/65Cu NMR for investigating and resolving inequivalent Cu sites, monitoring MOF phase changes, interrogating the Cu oxidation number, and characterizing the product of a MOF chemical reaction involving Cu(ii) reduction to Cu(i). A convenient avenue to acquire accurate 65Cu NMR spectra and NMR parameters from Cu(i) MOFs at a widely accessible magnetic field of 9.4 T is described, with a demonstrated practical application for tracking Cu(i) coordination evolution during MOF anion exchange. This work showcases the power of 63/65Cu solid-state NMR spectroscopy and DFT calculations for molecular-level characterization of Cu(i) centers in MOFs, along with the potential of this protocol for investigating a wide variety of MOF structural changes and processes important for practical applications. This approach has broad applications for examining Cu(i) centers in other weight-dilute systems.

11.
Foods ; 13(10)2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38790829

RESUMEN

Over the last decades, a significant rise in fruit consumption has been noticed as they contain numerous nutritional components, which has led to the rise in fruit production globally. However, fruits are highly liable to spoilage in nature and remain vulnerable to losses during the storage and preservation stages. Therefore, it is crucial to enhance the storage life and safeness of fruits for the consumers. To keep up the grade and prolong storage duration, various techniques are employed in the food sector. Among these, biopolymer coatings have gained widespread acceptance due to their improved characteristics and ideal substitution for synthetic polymer coatings. As there is concern regarding the safety of the consumers and sustainability, edible coatings have become a selective substitution for nurturing fruit quality and preventing decay. The application of polysaccharide-based edible coatings offers a versatile solution to prevent the passage of moisture, gases, and pathogens, which are considered major threats to fruit deterioration. Different polysaccharide substances such as chitin, pectin, carrageenan, cellulose, starch, etc., are extensively used for preparing edible coatings for a wide array of fruits. The implementation of coatings provides better preservation of the fruits such as mango, strawberry, pineapple, apple, etc. Furthermore, the inclusion of functional ingredients, including polyphenols, natural antioxidants, antimicrobials, and bio-nanomaterials, into the edible coating solution matrix adds to the nutritional, functional, and sensory attributes of the fruits. The blending of essential oil and active agents in polysaccharide-based coatings prevents the growth of food-borne pathogens and enhances the storage life of the pineapple, also improving the preservation of strawberries and mangoes. This paper aims to provide collective data regarding the utilization of polysaccharide-based edible coatings concerning their characteristics and advancements for fruit preservation.

12.
J Cell Mol Med ; 28(10): e18385, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38801405

RESUMEN

Autophagy may play an important role in the occurrence and development of glucocorticoid-induced osteonecrosis of the femoral head (GC-ONFH). Lithium is a classical autophagy regulator, and lithium can also activate osteogenic pathways, making it a highly promising therapeutic agent for GC-ONFH. We aimed to evaluate the potential therapeutic effect of lithium on GC-ONFH. For in vitro experiments, primary osteoblasts of rats were used for investigating the underlying mechanism of lithium's protective effect on GC-induced autophagy levels and osteogenic activity dysfunction. For in vivo experiments, a rat model of GC-ONFH was used for evaluating the therapeutic effect of oral lithium on GC-ONFH and underlying mechanism. Findings demonstrated that GC over-activated the autophagy of osteoblasts and reduced their osteogenic activity. Lithium reduced the over-activated autophagy of GC-treated osteoblasts through PI3K/AKT/mTOR signalling pathway and increased their osteogenic activity. Oral lithium reduced the osteonecrosis rates in a rat model of GC-ONFH, and restrained the increased expression of autophagy related proteins in bone tissues through PI3K/AKT/mTOR signalling pathway. In conclusion, lithium can restrain over-activated autophagy by activating PI3K/AKT/mTOR signalling pathway and up-regulate the expression of genes for bone formation both in GC induced osteoblasts and in a rat model of GC-ONFH. Lithium may be a promising therapeutic agent for GC-ONFH. However, the role of autophagy in the pathogenesis of GC-ONFH remains controversial. Studies are still needed to further explore the role of autophagy in the pathogenesis of GC-ONFH, and the efficacy of lithium in the treatment of GC-ONFH and its underlying mechanisms.


Asunto(s)
Autofagia , Necrosis de la Cabeza Femoral , Glucocorticoides , Litio , Osteoblastos , Transducción de Señal , Serina-Treonina Quinasas TOR , Animales , Autofagia/efectos de los fármacos , Glucocorticoides/farmacología , Glucocorticoides/efectos adversos , Ratas , Necrosis de la Cabeza Femoral/inducido químicamente , Necrosis de la Cabeza Femoral/patología , Necrosis de la Cabeza Femoral/tratamiento farmacológico , Necrosis de la Cabeza Femoral/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Transducción de Señal/efectos de los fármacos , Litio/farmacología , Osteoblastos/efectos de los fármacos , Osteoblastos/metabolismo , Masculino , Osteogénesis/efectos de los fármacos , Ratas Sprague-Dawley , Proteínas Proto-Oncogénicas c-akt/metabolismo , Modelos Animales de Enfermedad , Fosfatidilinositol 3-Quinasas/metabolismo , Cabeza Femoral/patología , Cabeza Femoral/efectos de los fármacos , Cabeza Femoral/metabolismo , Osteonecrosis/inducido químicamente , Osteonecrosis/patología , Osteonecrosis/tratamiento farmacológico , Osteonecrosis/metabolismo , Osteonecrosis/prevención & control
13.
J Transl Med ; 22(1): 381, 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38654380

RESUMEN

BACKGROUND: Gastric cancer (GC) is a common and aggressive type of cancer worldwide. Despite recent advancements in its treatment, the prognosis for patients with GC remains poor. Understanding the mechanisms of cell death in GC, particularly those related to mitochondrial function, is crucial for its development and progression. However, more research is needed to investigate the significance of the interaction between mitochondrial function and GC cell death. METHODS: We employed a robust computational framework to investigate the role of mitochondria-associated proteins in the progression of GC in a cohort of 1,199 GC patients. Ten machine learning algorithms were utilized and combined into 101 unique combinations. Ultimately, we developed a Mitochondrial-related-Score (MitoScore) using the machine learning model that exhibited the best performance. We observed the upregulation of LEMT2 and further explored its function in tumor progression. Mitochondrial functions were assessed by measuring mitochondrial ATP, mitochondrial membrane potential, and levels of lactate, pyruvate, and glucose. RESULTS: MitoScore showed significant correlations with GC immune and metabolic functions. The higher MitoScore subgroup exhibited enriched metabolic pathways and higher immune activity. Overexpression of LETM2 (leucine zipper and EF-hand containing transmembrane protein 2) significantly enhanced tumor proliferation and metastasis. LETM2 plays a role in promoting GC cell proliferation by activating the mTOR pathway, maintaining mitochondrial homeostasis, and promoting glycolysis. CONCLUSION: The powerful machine learning framework highlights the significant potential of MitoScore in providing valuable insights and accurate assessments for individuals with GC. This study also enhances our understanding of LETM2 as an oncogene signature in GC. LETM2 may promote tumor progression by maintaining mitochondrial health and activating glycolysis, offering potential targets for diagnosis, treatment, and prognosis of GC.


Asunto(s)
Aprendizaje Automático , Mitocondrias , Neoplasias Gástricas , Neoplasias Gástricas/patología , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Humanos , Mitocondrias/metabolismo , Pronóstico , Estudios de Cohortes , Masculino , Femenino , Modelos Biológicos , Proliferación Celular , Persona de Mediana Edad , Regulación Neoplásica de la Expresión Génica , Proteínas de la Membrana/metabolismo , Multiómica
14.
Adv Sci (Weinh) ; 11(24): e2306671, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38639383

RESUMEN

Cancer metastasis is the leading cause of mortality in patients with hepatocellular carcinoma (HCC). To meet the rapid malignant growth and transformation, tumor cells dramatically increase the consumption of nutrients, such as amino acids. Peptide transporter 1 (PEPT1), a key transporter for small peptides, has been found to be an effective and energy-saving intracellular source of amino acids that are required for the growth of tumor cells. Here, the role of PEPT1 in HCC metastasis and its underlying mechanisms is explored. PEPT1 is upregulated in HCC cells and tissues, and high PEPT1 expression is associated with poor prognosis in patients with HCC. PEPT1 overexpression dramatically promoted HCC cell migration, invasion, and lung metastasis, whereas its knockdown abolished these effects both in vitro and in vivo. Mechanistic analysis revealed that high PEPT1 expression increased cellular dipeptides in HCC cells that are responsible for activating the MAP4K4/G3BP2 signaling pathway, ultimately facilitating the phosphorylation of G3BP2 at Thr227 and enhancing HCC metastasis. Taken together, these findings suggest that PEPT1 acts as an oncogene in promoting HCC metastasis through dipeptide-induced MAP4K4/G3BP2 signaling and that the PEPT1/MAP4K4/G3BP2 axis can serve as a promising therapeutic target for metastatic HCC.


Asunto(s)
Carcinoma Hepatocelular , Dipéptidos , Neoplasias Hepáticas , Transportador de Péptidos 1 , Transducción de Señal , Animales , Humanos , Masculino , Ratones , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Movimiento Celular , Dipéptidos/metabolismo , Dipéptidos/farmacología , Modelos Animales de Enfermedad , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Ratones Desnudos , Metástasis de la Neoplasia , Transportador de Péptidos 1/metabolismo , Transportador de Péptidos 1/genética , Proteínas de Unión al ARN/metabolismo , Proteínas de Unión al ARN/genética
15.
Int J Biol Macromol ; 268(Pt 1): 131614, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38631567

RESUMEN

The global consumption of meat products is on the rise, leading to concerns about sustainability, fat content, and shelf life. Synthetic additives and preservatives used to extend the shelf life of meat often have negative health and environmental implications. Natural polysaccharides such as seed gums possess unique techno-functional properties, including water holding capacity, emulsifying, and film forming, offering potential alternatives in meat processing and preservation. This study explores the use of gums in meat and meat product processing and preservation. The water holding and emulsifying properties of gums can potentially bind fat and reduce overall lipid content, while their antimicrobial and film-forming properties can inhibit the microbial growth and reduce oxidation, thereby extending the shelf life. Incorporating gums as a fat replacer and edible coating shows promise for reducing fat content and extending the shelf life of meat and meat products.


Asunto(s)
Coloides , Conservación de Alimentos , Gomas de Plantas , Coloides/química , Gomas de Plantas/química , Conservación de Alimentos/métodos , Animales , Productos de la Carne/análisis , Productos de la Carne/microbiología , Manipulación de Alimentos/métodos , Carne
16.
FASEB J ; 38(7): e23594, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38573451

RESUMEN

A high prevalence of osteoarthritis (OA) has been observed among individuals living at high altitudes, and hypobaric hypoxia (HH) can cause bone mass and strength deterioration. However, the effect of HH on OA remains unclear. In this study, we aimed to explore the impact of HH on OA and its potential mechanisms. A rat knee OA model was established by surgery, and the rats were bred in an HH chamber simulating a high-altitude environment. Micro-computed tomography (Micro-CT), histological analysis, and RNA sequencing were performed to evaluate the effects of HH on OA in vivo. A hypoxic co-culture model of osteoclasts and osteoblasts was also established to determine their effects on chondrogenesis in vitro. Cartilage degeneration significantly worsened in the HH-OA group compared to that in the normoxia-OA (N-OA) group, 4 weeks after surgery. Micro-CT analysis revealed more deteriorated bone mass in the HH-OA group than in the N-OA group. Decreased hypoxia levels in the cartilage and enhanced hypoxia levels in the subchondral bone were observed in the HH-OA group. Furthermore, chondrocytes cultured in a conditioned medium from the hypoxic co-culture model showed decreased anabolism and extracellular matrix compared to those in the normoxic model. RNA sequencing analysis of the subchondral bone indicated that the glycolytic signaling pathway was highly activated in the HH-OA group. HH-related OA progression was associated with alterations in the oxygen environment and bone remodeling in the subchondral zone, which provided new insights into the pathogenesis of OA.


Asunto(s)
Osteoartritis , Oxígeno , Animales , Ratas , Microtomografía por Rayos X , Hipoxia , Osteoartritis/etiología , Remodelación Ósea
17.
ACS Nano ; 18(11): 7877-7889, 2024 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-38450636

RESUMEN

The octopus, as one of the most famous celebrities in bionics, has provided various inspirations for camouflage materials, soft-bodied robots, and flexible grabbers. The miniaturization of such structures will help the development of microrobots, microdelivery of drugs, and surface coating. With the lack of relevant effective preparation approaches, however, the generation of such octopus-like structures with a size of ∼1 µm or below is challenging. Here, we develop an approach based on laser-microdroplet interaction for generating an octopus-like structure with a size of ∼1 µm. The developed approach uses laser-microdroplet interaction to provide a large driving force of ∼107 Pa at a confined space (<1 µm), locally crumpling the precursor in the microdroplet. The locally crumpled particles possess both crumpled and uncrumpled structures that resemble an octopus's head and soft body. In the adhesion test, the octopus-like particles exhibit high adhesive properties in air, in water, and on a flexible substrate. In the electrochemical test, the octopus-like particles on flexible electrodes show good electrochemical and adhesive properties under hundreds of bending cycles. Benefiting from the combination of crumpled and uncrumpled morphologies, the created particles with octopus-like microstructure are demonstrated to possess comprehensive performance, exhibiting wide application potentials in the fields of microswimmers, surface coatings, and electrochemistry. Additionally, the method developed in this work has the advantages of concentrated energy in a confined space, displaying prospective potentials in micro- and nanoprocessing.

18.
Heliyon ; 10(5): e27150, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38449652

RESUMEN

Background: Anaplastic thyroid carcinoma (ATC), a rare but highly aggressive endocrine malignancy, is characterized by a significant presence of cancer stem-like cells (CSCs). These CSCs, known for their self-renewal and differentiation capacities, contribute to various aggressive tumor properties, including recurrence, metastasis, heterogeneity, multidrug resistance, and radiation resistance. Despite their critical role, the regulatory mechanisms of CSCs in ATC remain poorly elucidated, posing challenges in effectively targeting these cells for treatment. Methods: To delve into this, we employed the single sample gene set enrichment analysis (ssGSEA) algorithm to evaluate the stemness of samples in combined datasets. Samples were then classified into high and low stemness subgroups based on their average stemness scores. Differential gene expression between these subgroups was analyzed. We further explored the association of candidate genes with patient prognosis. Additionally, we conducted gene set enrichment analysis (GSEA) and a series of cell biology experiments to validate the role of DEP domain-containing protein 1 (DEPDC1) in fostering CSC-like traits and regulating the malignant phenotypes of ATC. Results: Our investigation demonstrated that DEPDC1 was significantly upregulated in CSCs and is abundantly expressed in ATC tissues. In vitro assays revealed that knockdown of DEPDC1 markedly inhibited tumor sphere formation and attenuated the proliferation, invasion, and migration of ATC cells. This silencing also resulted in reduced expression of stemness markers associated with CSCs. Furthermore, our GSEA findings linked high DEPDC1 expression to cell cycle progression and the maintenance of tumor cell stemness, with DEPDC1 knockdown disrupting these signaling pathways. Collectively, our results position DEPDC1 as a pivotal regulator of CSC-like characteristics in ATC, where aberrant DEPDC1 expression amplifies stemness properties and fuels the cancer's aggressive behavior. Consequently, DEPDC1 emerges as a promising therapeutic target for ATC management. In summary, this study underscores the pivotal role of DEPDC1 in modulating CSC-like features in ATC, offering new avenues for targeted therapy in this challenging malignancy.

19.
Food Chem ; 447: 138952, 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-38461720

RESUMEN

The edible coating is proved to be a convenient approach for fruit preservation. Among these published explorations, naturally sourced macromolecules and green crosslinking strategies gain attention. This work centers on edible coatings containing Ca2+ as crosslinker for the first time, delving into crosslinking mechanisms, include alginate, chitosan, Aloe vera gel, gums, etc. Additionally, the crucial functions of Ca2+ in fruit's quality control are also elaborated in-depth, involving cell wall, calmodulin, antioxidant, etc. Through a comprehensive review, it becomes evident that Ca2+ plays a dual role in fruit edible coating. Specifically, Ca2+ constructs a three-dimensional dense network structure with polymers through ionic bonding. Moreover, Ca2+ acts directly with cell wall to maintain fruit firmness and serve as a second messenger to participate secondary physiological metabolism. In brief, coatings containing Ca2+ present remarkable effects in preserving fruit and this work may provide guidance for Ca2+ related fruit preservation coatings.


Asunto(s)
Películas Comestibles , Conservación de Alimentos , Conservación de Alimentos/métodos , Calcio/análisis , Polímeros/análisis , Frutas/química
20.
Phys Rev Lett ; 132(10): 104001, 2024 Mar 08.
Artículo en Inglés | MEDLINE | ID: mdl-38518322

RESUMEN

Phototaxis phenomenon is fundamental and critical for optical manipulation of micro-objects. Here, we report the size-dependent negative or positive phototaxis behaviors for microdroplets containing interfacial energy absorber flying in a laser. The critical diameters for such negative-to-positive turnover are studied through both experiments and simulation with different liquids and absorbers, which establishes the mechanism and reveals the role of both the liquid and the absorber inside the microdroplets. This study offers new insight for the manipulation of the phototaxis behavior of micro-objects, showing potential applications in optical trapping and transporting systems that involve light-microdroplet interactions.

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