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1.
Cell ; 175(7): 1972-1988.e16, 2018 12 13.
Artículo en Inglés | MEDLINE | ID: mdl-30550791

RESUMEN

In vitro cancer cultures, including three-dimensional organoids, typically contain exclusively neoplastic epithelium but require artificial reconstitution to recapitulate the tumor microenvironment (TME). The co-culture of primary tumor epithelia with endogenous, syngeneic tumor-infiltrating lymphocytes (TILs) as a cohesive unit has been particularly elusive. Here, an air-liquid interface (ALI) method propagated patient-derived organoids (PDOs) from >100 human biopsies or mouse tumors in syngeneic immunocompetent hosts as tumor epithelia with native embedded immune cells (T, B, NK, macrophages). Robust droplet-based, single-cell simultaneous determination of gene expression and immune repertoire indicated that PDO TILs accurately preserved the original tumor T cell receptor (TCR) spectrum. Crucially, human and murine PDOs successfully modeled immune checkpoint blockade (ICB) with anti-PD-1- and/or anti-PD-L1 expanding and activating tumor antigen-specific TILs and eliciting tumor cytotoxicity. Organoid-based propagation of primary tumor epithelium en bloc with endogenous immune stroma should enable immuno-oncology investigations within the TME and facilitate personalized immunotherapy testing.


Asunto(s)
Modelos Inmunológicos , Neoplasias Experimentales/inmunología , Organoides/inmunología , Receptores de Antígenos de Linfocitos T/inmunología , Microambiente Tumoral/inmunología , Animales , Antígeno B7-H1/inmunología , Técnicas de Cocultivo , Femenino , Humanos , Inmunoterapia , Masculino , Ratones , Ratones Endogámicos BALB C , Proteínas de Neoplasias/inmunología , Neoplasias Experimentales/patología , Neoplasias Experimentales/terapia , Organoides/patología
2.
J Biol Chem ; 299(8): 105021, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37423299

RESUMEN

Recurrent hormone receptor-positive (HR+) breast cancer kills more than 600,000 women annually. Although HR+ breast cancers typically respond well to therapies, approximately 30% of patients relapse. At this stage, the tumors are usually metastatic and incurable. Resistance to therapy, particularly endocrine therapy is typically thought to be tumor intrinsic (e.g., estrogen receptor mutations). However, tumor-extrinsic factors also contribute to resistance. For example, stromal cells, such as cancer-associated fibroblasts (CAFs), residing in the tumor microenvironment, are known to stimulate resistance and disease recurrence. Recurrence in HR+ disease has been difficult to study due to the prolonged clinical course, complex nature of resistance, and lack of appropriate model systems. Existing HR+ models are limited to HR+ cell lines, a few HR+ organoid models, and xenograft models that all lack components of the human stroma. Therefore, there is an urgent need for more clinically relevant models to study the complex nature of recurrent HR+ breast cancer, and the factors contributing to treatment relapse. Here, we present an optimized protocol that allows a high take-rate, and simultaneous propagation of patient-derived organoids (PDOs) and matching CAFs, from primary and metastatic HR+ breast cancers. Our protocol allows for long-term culturing of HR+ PDOs that retain estrogen receptor expression and show responsiveness to hormone therapy. We further show the functional utility of this system by identifying CAF-secreted cytokines, such as growth-regulated oncogene α , as stroma-derived resistance drivers to endocrine therapy in HR+ PDOs.


Asunto(s)
Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Receptores de Estrógenos/genética , Receptores de Estrógenos/metabolismo , Recurrencia Local de Neoplasia/patología , Fibroblastos/metabolismo , Organoides/metabolismo , Microambiente Tumoral
3.
Mol Cancer ; 23(1): 12, 2024 01 10.
Artículo en Inglés | MEDLINE | ID: mdl-38200517

RESUMEN

BACKGROUND: Malignant peritoneal mesothelioma (MPM) is an extremely rare and highly invasive tumor. Due to the lack of accurate models that reflect the biological characteristics of primary tumors, studying MPM remains challenging and is associated with an exceedingly unfavorable prognosis. This study was aimed to establish a new potential preclinical model for MPM using patient-derived MPM organoids (MPMOs) and to comprehensively evaluate the practicality of this model in medical research and its feasibility in guiding individualized patient treatment. METHODS: MPMOs were constructed using tumor tissue from MPM patients. Histopathological analysis and whole genome sequencing (WGS) were employed to determine the ability of MPMOs to replicate the original tumor's genetic and histological characteristics. The subcutaneous and orthotopic xenograft models were employed to assess the feasibility of establishing an in vivo model of MPM. MPMOs were also used to conduct drug screening and compare the results with retrospective analysis of patients after treatment, in order to evaluate the potential of MPMOs in predicting the effectiveness of drugs in MPM patients. RESULTS: We successfully established a culture method for human MPM organoids using tumor tissue from MPM patients and provided a comprehensive description of the necessary medium components for MPMOs. Pathological examination and WGS revealed that MPMOs accurately represented the histological characteristics and genomic heterogeneity of the original tumors. In terms of application, the success rate of creating subcutaneous and orthotopic xenograft models using MPMOs was 88% and 100% respectively. Drug sensitivity assays demonstrated that MPMOs have different medication responses, and these differences were compatible with the real situation of the patients. CONCLUSION: This study presents a method for generating human MPM organoids, which can serve as a valuable research tool and contribute to the advancement of MPM research. Additionally, these organoids can be utilized as a means to evaluate the effectiveness of drug treatments for MPM patients, offering a model for personalized treatment approaches.


Asunto(s)
Mesotelioma Maligno , Mesilatos , Neoplasias Peritoneales , Piperidinas , Humanos , Animales , Estudios Retrospectivos , Neoplasias Peritoneales/tratamiento farmacológico , Neoplasias Peritoneales/genética , Modelos Animales de Enfermedad , Organoides
4.
Exp Cell Res ; 425(1): 113538, 2023 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-36871856

RESUMEN

Breast cancer has become the highest incidence of cancer in women. It was extensively and deeply studied by biologists and medical workers worldwide. However, the meaningful results in lab researches cannot be realized in clinical, and a part of new drugs in clinical experiments do not obtain as good results as the preclinical researches. It is urgently that promote a kind of breast cancer research models that can get study results closer to the physiological condition of the human body. Patient-derived models (PDMs) originating from clinical tumor, contain primary elements of tumor and maintain key clinical features of tumor. So they are promising research models to facilitate laboratory researches translate to clinical application, and predict the treatment outcome of patients. In this review, we summarize the establishment of PDMs of breast cancer, reviewed the application of PDMs in clinical translational researches and personalized precision medicine with breast cancer as an example, to improve the understanding of PDMs among researchers and clinician, facilitate them to use PDMs on a large scale of breast cancer researches and promote the clinical translation of laboratory research and new drug development.


Asunto(s)
Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Investigación , Medicina de Precisión/métodos , Ensayos Antitumor por Modelo de Xenoinjerto
5.
Appetite ; 199: 107400, 2024 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-38735306

RESUMEN

The EU Farm to Fork strategy (F2F) promotes the compulsory adoption of a nutritional front of pack label to improve the diets of the citizens, supporting healthier food choices. In the public debate, Nutri-Score (NS) is the most favored candidate. Although being widely supported, oppositions on the political and producer levels are raised against the NS, due to the economic impact it could have on specific food sector, and specifically on Geographical Indications (GIs). Recent literature has stressed the need to explore it in more detail. The current study contributes to fill this gap by analyzing consumers' monetary preferences for GI products labelled with different NS levels. An incentivized non-hypothetical experiment was conducted on 188 Italian consumers. Different products representing different levels of NS were used. Specifically, a conventional pasta and the Pasta di Gragnano PGI (NS = A), a conventional flatbread (piadina) and the Piadina Romagnola PGI (NSC), and a conventional hard cheese and the Parmigiano Reggiano PDO (NS = D) were considered in the survey. Results reveal that the NS elicits favorable responses and unfavorable reactions in consumers' preferences, aligning with expectations for A and D scores, respectively. The perceived healthiness of the product significantly affects consumers' WTP, increasing it. Results stress the need to have effective communication strategies within the EU to reach the F2F goals. NS diminishes the premium in prices associated with GIs independently from its level, when considering those consumers who value more the GIs. However, the most well-known GIs does not suffer from this negative effect of the NS, as the positive value associated to the GI offset the negative effect of the NS.


Asunto(s)
Conducta de Elección , Comportamiento del Consumidor , Etiquetado de Alimentos , Preferencias Alimentarias , Valor Nutritivo , Humanos , Preferencias Alimentarias/psicología , Femenino , Masculino , Italia , Adulto , Etiquetado de Alimentos/métodos , Persona de Mediana Edad , Adulto Joven , Encuestas y Cuestionarios , Dieta Saludable/psicología , Dieta Saludable/economía , Adolescente
6.
Sensors (Basel) ; 24(15)2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-39124017

RESUMEN

Pure SnO2 and 1 at.% PdO-SnO2 materials were prepared using a simple hydrothermal method. The micromorphology and element valence state of the material were characterized using XRD, SEM, TEM, and XPS methods. The SEM results showed that the prepared material had a two-dimensional nanosheet morphology, and the formation of PdO and SnO2 heterostructures was validated through TEM. Due to the influence of the heterojunction, in the XPS test, the energy spectrum peaks of Sn and O in PdO-SnO2 were shifted by 0.2 eV compared with SnO2. The PdO-SnO2 sensor showed improved ethanol sensing performance compared to the pure SnO2 sensor, since it benefited from the large specific surface area of the nanosheet structure, the modulation effect of the PdO-SnO2 heterojunction on resistance, and the catalyst effect of PdO on the adsorption of oxygen. A DFT calculation study of the ethanol adsorption characteristics of the PdO-SnO2 surface was conducted to provide a detailed explanation of the gas-sensing mechanism. PdO was found to improve the reducibility of ethanol, enhance the adsorption of ethanol's methyl group, and increase the number of adsorption sites. A synergistic effect based on the continuous adsorption sites was also deduced.

7.
Aesthetic Plast Surg ; 48(9): 1706-1714, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38519570

RESUMEN

BACKGROUND: Traditional facial aging surgeries have risks and extended recovery times, leading to a demand for minimally invasive alternatives. PDO (polydioxanone) threads, which are absorbable sutures that stimulate collagen production and tissue contraction, offer improved aesthetic outcomes. This paper evaluates the combined use of PDO thread mid-cheek lift and lower blepharoplasty for facial rejuvenation. METHODS: This retrospective study compared outcomes in patients undergoing lower blepharoplasty combined with a mid-face lift using PDO threads versus those undergoing only lower blepharoplasty. Focused on individuals with baggy lower eyelids and pronounced nasolabial folds, outcome measures included the Modified Fitzpatrick wrinkle scale, Allergan® midface volume deficit scale, Width of inter zygomatic distance, Patient and Observer Scar Assessment Scale, and patient satisfaction questionnaires, assessed at baseline, 3 months, and 1 year postoperatively. RESULTS: The combined procedure demonstrated superior aesthetic outcomes and higher patient satisfaction compared to lower blepharoplasty alone. Improvements were more significant in wrinkle reduction, midface volume, and inter-zygomatic distance in the combined procedure group. Although the combined procedure had a longer mean operation time, scar assessment scores were similar between both groups, with no complications reported. CONCLUSION: The combination of lower blepharoplasty and mid-face lift using PDO threads is a comprehensive and effective approach for facial rejuvenation. It significantly enhances wrinkle reduction, mid-face lifting, and patient satisfaction. Ultrasound-guided thread lifting, a method of assessing and performing mid-face lifting, proves to be safe and efficient. This approach holds promise as a future option in cosmetic anti-aging surgery, presenting a minimally invasive alternative with natural-looking results and reduced downtime. LEVEL OF EVIDENCE II: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors https://link.springer.com/journal/00266 .


Asunto(s)
Blefaroplastia , Satisfacción del Paciente , Polidioxanona , Rejuvenecimiento , Ritidoplastia , Envejecimiento de la Piel , Humanos , Blefaroplastia/métodos , Estudios Retrospectivos , Femenino , Persona de Mediana Edad , Ritidoplastia/métodos , Masculino , Resultado del Tratamiento , Estética , Anciano , Adulto , Técnicas de Sutura , Suturas , Estudios de Cohortes
8.
Int J Mol Sci ; 25(10)2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38791392

RESUMEN

Malignant pleural mesothelioma (MPM) remains an incurable disease. This is partly due to the lack of experimental models that fully recapitulate the complexity and heterogeneity of MPM, a major challenge for therapeutic management of the disease. In addition, the contribution of the MPM microenvironment is relevant for the adaptive response to therapy. We established mesothelioma patient-derived organoid (mPDO) cultures from MPM pleural effusions and tested their response to pemetrexed and cisplatin. We aimed to evaluate the contribution of mesothelioma-associated fibroblasts (MAFs) to the response to pemetrexed and cisplatin (P+C). Organoid cultures were obtained from eight MPM patients using specific growth media and conditions to expand pleural effusion-derived cells. Flow cytometry was used to verify the similarity of the organoid cultures to the original samples. MAFs were isolated and co-cultured with mPDOs, and the addition of MAFs reduced the sensitivity of mPDOs to P+C. Organoid formation and expression of cancer stem cell markers such as ABCG2, NANOG, and CD44 were altered by conditioned media from treated MAFs. We identified IL-6 as the major contributor to the attenuated response to chemotherapy. IL-6 secretion by MAFs is correlated with increased resistance of mPDOs to pemetrexed and cisplatin.


Asunto(s)
Fibroblastos Asociados al Cáncer , Cisplatino , Interleucina-6 , Mesotelioma Maligno , Organoides , Pemetrexed , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Antineoplásicos/farmacología , Fibroblastos Asociados al Cáncer/metabolismo , Fibroblastos Asociados al Cáncer/efectos de los fármacos , Fibroblastos Asociados al Cáncer/patología , Cisplatino/farmacología , Fibroblastos/metabolismo , Fibroblastos/efectos de los fármacos , Fibroblastos/patología , Interleucina-6/metabolismo , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Mesotelioma/patología , Mesotelioma/tratamiento farmacológico , Mesotelioma/metabolismo , Mesotelioma Maligno/tratamiento farmacológico , Mesotelioma Maligno/patología , Mesotelioma Maligno/metabolismo , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/efectos de los fármacos , Células Madre Neoplásicas/patología , Organoides/metabolismo , Organoides/efectos de los fármacos , Organoides/patología , Pemetrexed/farmacología , Microambiente Tumoral/efectos de los fármacos
9.
J Sci Food Agric ; 104(11): 6388-6396, 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-38380878

RESUMEN

Cheese, a fundamental component of the human diet and a cornerstone of the global food economy, has a significance beyond its role as a commodity, playing a crucial part in the cultural identity of various communities. The intricate natural aging process known as maturation involves a series of reactions that induce changes in the cheese's physical, biochemical, microbiological, and particularly sensory characteristics, making it a complex aspect of cheese production. Recently, the adoption of omics sciences (e.g., metagenomics, metabolomics, proteomics) has emerged as a new trend in studies related to protected designation of origin (PDO) cheese. This mini-summary aims to outline the relationship between omics studies in these food matrices and all the sustainability facets of the production chain in general, and to discuss and recognize that the importance of these studies goes beyond comprehending the cheese biome and extends to fostering and ensuring the sustainability of the production chain. In this context, numerous studies in recent years have linked the identification of intrinsic characteristics of PDO cheeses through omics sciences to crucial sustainability themes such as territoriality, biodiversity, and the preservation of product authenticity. The trajectory suggests that, increasingly, multidisciplinary studies spanning various omics sciences will not only contribute to the characterization of these products but will also address sustainability aspects directly related to the production chain (e.g., authenticity, microbial biodiversity, functionality). This expansion underscores the multidisciplinary nature of these studies, broadening their social impact beyond the academic realm. Consequently, these pivotal studies play a crucial role in advancing discussions on PDO products and sustainability. © 2024 Society of Chemical Industry.


Asunto(s)
Queso , Metabolómica , Metagenómica , Proteómica , Queso/análisis , Queso/microbiología , Humanos , Animales , Biodiversidad
10.
BMC Med ; 21(1): 336, 2023 09 04.
Artículo en Inglés | MEDLINE | ID: mdl-37667332

RESUMEN

BACKGROUND: Colorectal adenoma (CA), especially high-risk CA (HRCA), is a precancerous lesion with high prevalence and recurrence rate and accounts for about 90% incidence of sporadic colorectal cancer cases worldwide. Currently, recurrent CA can only be treated with repeated invasive polypectomies, while safe and promising pharmaceutical invention strategies are still missing due to the lack of reliable in vitro model for CA-related drug screening. METHODS: We have established a large-scale patient-derived high-risk colorectal adenoma organoid (HRCA-PDO) biobank containing 37 PDO lines derived from 33 patients and then conducted a series of high-throughput and high-content HRCA drug screening. RESULTS: We established the primary culture system with the non-WNT3a medium which highly improved the purity while maintained the viability of HRCA-PDOs. We also proved that the HRCA-PDOs replicated the histological features, cellular diversity, genetic mutations, and molecular characteristics of the primary adenomas. Especially, we identified the dysregulated stem genes including LGR5, c-Myc, and OLFM4 as the markers of adenoma, which are well preserved in HRCA-PDOs. Based on the HRCA-PDO biobank, a customized 139 compound library was applied for drug screening. Four drugs including metformin, BMS754807, panobinostat and AT9283 were screened out as potential hits with generally consistent inhibitory efficacy on HRCA-PDOs. As a representative, metformin was discovered to hinder HRCA-PDO growth in vitro and in vivo by restricting the stemness maintenance. CONCLUSIONS: This study established a promising HRCA-PDO biobank and conducted the first high-throughput and high-content HRCA drug screening in order to shed light on the prevention of colorectal cancer.


Asunto(s)
Adenoma , Neoplasias Colorrectales , Metformina , Humanos , Bancos de Muestras Biológicas , Evaluación Preclínica de Medicamentos , Organoides , Adenoma/tratamiento farmacológico , Adenoma/genética , Neoplasias Colorrectales/tratamiento farmacológico
11.
Small ; 19(28): e2208026, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37013451

RESUMEN

Hydrogen (H2 ) sensing materials such as semiconductor metal oxides may suffer from poor long-term stability against humidity and unsatisfactory selectivity against other interfering gases. To address the above issues, highly stable and selective H2 sensing built with palladium oxide nanodots decorating aluminum oxide nanosheets (PdO NDs//Al2 O3 NSs) has been achieved via combined template synthesis, photochemical deposition, and oxidation. Typically, the PdO NDs//Al2 O3 NSs are observed with thin NSs (≈17 nm thick) decorated with nanodots (≈3.3 nm in diameter). Beneficially, the sensor prototypes built with PdO NDs//Al2 O3 NSs show excellent long-term stability for 278 days, high selectivity against interfering gases, and outstanding stability against humidity at 300 °C. Remarkably, the sensor prototypes enable detection of a wide-range of 20 ppm - 6 V/V% H2 , and the response and recovery times are ≈5 and 16 s to 1 V/V% H2 , respectively. Theoretically, the heterojunctions of PdO NDs-Al2 O3 NSs with a large specific surface ratio and Al2 O3 NSs as the support exhibit excellent stability and selective H2 sensing. Practically, a sensing device integrated with the PdO NDs//Al2 O3 NSs sensor prototype is simulated for detecting H2 with reliable sensing response.

12.
Appl Microbiol Biotechnol ; 107(5-6): 1875-1886, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36773061

RESUMEN

Milk is one of the most nutritionally complete foods and plays an important role in the human diet. Buffalo milk represents 15% of worldwide milk production and is an important source of bioactive compounds. Buffalo milk has a great market in the Mediterranean area, and dairy products, such as Mozzarella and Ricotta di Bufala Campana, obtained with the Italian Mediterranean buffalo milk, are acknowledged with the Protected Designation of Origin (PDO). This study aimed to characterize, using high-throughput sequencing of the 16S rRNA gene, the milk core microbiome of water buffalo rises in the Amaseno Valley included in the Mozzarella PDO region. The principal features of the core and the auxiliary buffalo milk microbiome are the predominance of Firmicutes and Lactococcus, one of the most important lactic acid bacteria (LAB) taxa in the dairy industry. The comparative analysis of the core microbiomes indicated that the milk of the Italian Mediterranean Buffalo and other mammals share the presence of Streptococcus-affiliated OTUs (operational taxonomic units). Our data also demonstrated that the core microbiome of milk samples collected from PDO and non-PDO regions differ in the number and type of taxa. KEY POINTS: • Buffalo milk and their derivate products are becoming more popular worldwide. • Dairy locations and practice management affect the structure of the milk microbiota. • Next-generation sequencing (NGS) analysis allows to identify the features of the Italian Buffalo milk microbiome.


Asunto(s)
Queso , Leche , Animales , Humanos , Leche/microbiología , Búfalos , ARN Ribosómico 16S , Italia , Queso/análisis
13.
J Dairy Sci ; 106(10): 6646-6654, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37164852

RESUMEN

Although there are several studies comparing organic and conventional milk characteristics, very few focused on dairy processed products such as cheese. Thus, this study aimed for a detailed controlled examination of gross composition, minerals, and the fatty acid profile of organic (ORG) and conventional (CON) Italian cheeses from parallel production. Four Italian cheese types were analyzed: Latteria (ORG, n = 9; CON, n = 10); Asiago Protected Designation of Origin (PDO) fresco (ORG, n = 9; CON, n = 9); Caciotta (ORG, n = 8; CON, n = 8); and Mozzarella Traditional Specialty Guaranteed (TSG; ORG, n = 14; CON, n = 14). Cheese samples were collected from September 2020 to August 2021. Gross composition, minerals, and fatty acids were determined using infrared spectroscopy. Within each cheese type, paired ORG and CON samples were compared using a nonparametric Wilcoxon signed-rank test. Latteria showed lower PUFA, n-3, and n-6 content, and greater Fe, K, C10:0, C12:0, and C16:0 content in ORG than in CON. Asiago PDO fresco showed lower protein and Zn content and greater salt, ash, and Na content in ORG than in CON. Caciotta showed lower ash, n-3, and n-6 content and greater K, C4:0, C8:0, C10:0, C14:0, and C16:0 content in ORG than in CON. Mozzarella TSG showed lower fat and, therefore, fatty acid content, and greater moisture, ash, and Mg content in ORG than in CON. In conclusion, few significant differences in chemical composition were observed between ORG and CON cheeses, regardless of the type considered. Moreover, Asiago PDO fresco showed fewer significant differences between ORG and CON compared with Latteria, Caciotta, and Mozzarella TSG.


Asunto(s)
Queso , Animales , Leche/química , Ácidos Grasos/análisis , Minerales/análisis , Italia
14.
J Dairy Res ; : 1-4, 2023 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-36799037

RESUMEN

Health-conscious consumers are increasingly paying attention to healthy diets and focusing on natural bioactive compounds in foods and their effects on mental health. This opens new opportunities for the study of artisanal cheeses as biofunctional foods. In the work described in this Research Communication, the gamma-aminobutyric acid (GABA) content of seven different Portuguese cheeses produced from unpasteurized cow, sheep, and goat milk and granted with protected designation of origin (PDO) status was analysed. The PDO cheeses made from cow milk analysed in this study were São Jorge (3, 4, 7, 12 and 24 months of maturation) and Pico cheeses. PDO cheeses made from sheep milk were Serra da Estrela, Serpa, Nisa and Azeitão. Cheeses made from sheep and goat milk included Beira Baixa yellow cheese. The GABA content in the Azorean PDO cheeses (made from cow milk) ranged from 1.23 to 2.64 g/kg of cheese. Higher variations in GABA content were observed in cheeses made from sheep and goat milk (0.73-2.31 g/kg). This study provides information on the GABA content in different Portuguese PDO cheeses and shows that hard or semi-hard ripened cheeses are a suitable matrix for GABA production by lactic acid bacteria.

15.
Nano Lett ; 22(7): 2769-2779, 2022 04 13.
Artículo en Inglés | MEDLINE | ID: mdl-35333538

RESUMEN

Treatments for low colorectal cancer (CRC) remain a great challenge due to the heavy physical and psychological burdens of colostomy, strong drug toxicity in chemotherapy, and myelosuppression-/chemoradiation-related gastrointestinal symptoms. In this study, a highly biosafe and effective tumor cell dissociation-based low CRC treatment modality has been verified on both PDOs in vitro and colorectal tumor models in vivo. Notably, controllable EDTA release at the tumor sites was achieved by the LDH degradation in response to a slightly acidic microenvironment of low CRC tumors. Resultantly, the intratumoral E-cadherin for intercellular junctions of low CRC tumors was effectively destroyed via Ca2+ depletion by released EDTA from the interlayers, initiating remarkable tumor cell dissociation and resultant tumor disaggregation/removal via defecation. Dissociated tumor cells were prevailingly enveloped by LDH/EDTA, which prevented them from readhering to adjacent tissues, providing an unprecedented, efficient and safe therapeutic modality for low CRC, which will benefit patients suffering low CRC.


Asunto(s)
Cadherinas , Neoplasias Colorrectales , Línea Celular Tumoral , Neoplasias Colorrectales/patología , Ácido Edético/farmacología , Ácido Edético/uso terapéutico , Humanos , Microambiente Tumoral
16.
Molecules ; 28(11)2023 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-37299009

RESUMEN

The crystal morphology of high energetic materials plays a crucial role in aspects of their safety performance such as impact sensitivity. In order to reveal the crystal morphology of ammonium dinitramide/pyrazine-1,4-dioxide (ADN/PDO) cocrystal at different temperatures, the modified attachment energy model (MAE) was used at 298, 303, 308, and 313 K to predict the morphology of the ADN/PDO cocrystal under vacuum and ethanol. The results showed that under vacuum conditions, five growth planes of the ADN/PDO cocrystal were given, which were (1 0 0), (0 1 1), (1 1 0), (1 1 -1), and (2 0 -2). Among them, the ratios of the (1 0 0) and (0 1 1) planes were 40.744% and 26.208%, respectively. In the (0 1 1) crystal plane, the value of S was 1.513. The (0 1 1) crystal plane was more conducive to the adsorption of ethanol molecules. The order of binding energy between the ADN/PDO cocrystal and ethanol solvent was (0 1 1) > (1 1 -1) > (2 0 -2) > (1 1 0) > (1 0 0). The radial distribution function analysis revealed that there were hydrogen bonds between the ethanol and the ADN cations, van der Waals interactions with the ADN anions. As the temperature increased, the aspect ratio of the ADN/PDO cocrystal was reduced, making the crystal more spherical, which helped to further reduce the sensitivity of this explosive.


Asunto(s)
Etanol , Pirazinas , Temperatura , Nitritos
17.
Molecules ; 28(20)2023 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-37894668

RESUMEN

The C-3 modification of 1H-indazole has produced active pharmaceuticals for the treatment of cancer and HIV. But, so far, this transformation has seemed less available, due to the lack of efficient C-C bond formation at the less reactive C-3 position. In this work, a series of silica gel-supported PdO2 nanoparticles of 25-66 nm size were prepared by ball milling silica gel with divalent palladium precursors, and then employed as catalysts for the Suzuki-Miyaura cross-coupling of 1H-indazole derivative with phenylboronic acid. All the synthesized catalysts showed much higher cross-coupling yields than their palladium precursors, and could also be reused three times without losing high activity and selectivity in a toluene/water/ethanol mixed solvent. Although the palladium precursors showed an order of activity of PdCl2(dppf, 1,1'-bis(diphenylphosphino)ferrocene) > PdCl2(dtbpf, 1,1'-bis(di-tert-butylphosphino)ferrocene) > Pd(OAc, acetate)2, the synthesized catalysts showed an order of C1 (from Pd(OAc)2) > C3 (from PdCl2(dtbpf)) > C2 (from PdCl2(dppf)), which conformed to the orders of BET (Brunauer-Emmett-Teller) surface areas and acidities of these catalysts. Notably, the most inexpensive Pd(OAc)2 can be used as a palladium precursor for the synthesis of the best catalyst through simple ball milling. This work provides a highly active and inexpensive series of catalysts for C-3 modification of 1H-indazole, which are significant for the large-scale production of 1H-indazole-based pharmaceuticals.

18.
Chemistry ; 28(6): e202103538, 2022 Jan 27.
Artículo en Inglés | MEDLINE | ID: mdl-34850478

RESUMEN

The new nanocomposites, Pd/C/ZrO2 , PdO/ZrO2, and Pd/PdO/ZrO2 , were prepared by thermal conversion of Pd@UiO-66-Zr-NH2 (MOF) in nitrogen or air atmosphere. The presence of Pd nanoparticles, uniformly distributed on the ZrO2 or C/ZrO2 matrix, was evidenced by transmission electron microscopy, scanning electron microscopy (SEM), Raman and X-ray Photoelectron Spectroscopy (XPS) methods. All pyrolysed composites retained the shape of the MOF template. They catalyze carbonylative Suzuki coupling under 1 atm CO with an efficiency significantly higher than the original Pd@UiO-66-Zr-NH2 . The most active PdO/ZrO2 composite, formed benzophenone with TOF up to 1600 h-1 , while by using Pd@UiO-66-Zr-NH2 , much lower TOF values, 51-95 h-1 , were achieved. After the reaction, PdO/ZrO2 was recovered with the same composition and catalytic activity. Very good results were also obtained in the transfer hydrogenation of benzophenones to alcohols with Pd/C/ZrO2 and PdO/ZrO2 catalysts under microwave irradiation.

19.
Nanotechnology ; 33(27)2022 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-35354121

RESUMEN

Strong demand for renewable energy resources and clean environments have inspired scientists and researchers across the globe to carry out research activities on energy provision, conversion, and storage devices. In this context, development of outperform, stable, and durable electrocatalysts has been identified as one of the major objectives for oxygen evolution reaction (OER). Herein, we offer facile approach for the deposition of few palladium oxide (PdO) nanoparticles on the cobalt-nickel bi-metallic sulphide (CoNi2S4) microstructures represented as PdO@ CoNi2S4using ultraviolet light (UV) reduction method. The morphology, crystalline structure, and chemical composition of the as-prepared PdO@ CoNi2S4composite were probed through scanning electron microscopy, powder x-ray diffraction, high resolution transmission electron microscopy, energy dispersive spectroscopy and x-ray photoelectron spectroscopy techniques. The combined physical characterization results revealed that ultraviolet light (UV) light promoted the facile deposition of PdO nanoparticles of 10 nm size onto the CoNi2S4and the fabricated PdO@ CoNi2S4composite has a remarkable activity towards OER in alkaline media. Significantly, it exhibited a low onset potential of 1.41 V versus reversible hydrogen electrode (RHE) and a low overpotential of 230 mV at 10 mA cm-2. Additionally, the fabricated PdO@ CoNi2S4composite has a marked stability of 45 h. Electrochemical impedance spectroscopy has shown that the PdO@CoNi2S4composite has a low charge transfer resistance of 86.3 Ohms, which favours the OER kinetics. The PdO@ CoNi2S4composite provided the multiple number of active sites, which favoured the enhanced OER activity. Taken together, this new class of material could be utilized in energy conversion and storage as well as sensing applications.

20.
World J Surg Oncol ; 20(1): 37, 2022 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-35177071

RESUMEN

BACKGROUND: As reported, preclinical animal models differ greatly from the human body. The evaluation model may be the colossal obstacle for scientific research and anticancer drug development. Therefore, it is essential to propose efficient evaluation systems similar to clinical practice for cancer research. MAIN BODY: While it has emerged for decades, the development of patient-derived xenografts, patient-derived organoid and patient-derived cell used to be limited. As the requirements for anticancer drug evaluation increases, patient-derived models developed rapidly recently, which is widely applied in basic research, drug development, and clinical application and achieved remarkable progress. However, there still lack systematic comparison and summarize reports for patient-derived models. In the current review, the development, applications, strengths, and challenges of patient-derived models in cancer research were characterized. CONCLUSION: Patient-derived models are an indispensable approach for cancer research and human health.


Asunto(s)
Antineoplásicos , Neoplasias , Animales , Antineoplásicos/uso terapéutico , Modelos Animales de Enfermedad , Xenoinjertos , Humanos , Neoplasias/tratamiento farmacológico , Organoides , Ensayos Antitumor por Modelo de Xenoinjerto
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