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1.
Neuropathol Appl Neurobiol ; 50(4): e12996, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38982616

RESUMEN

AIM: Systemic amyloidosis is a condition in which misfolded amyloid fibrils are deposited within tissues. Amyloid myopathy is a rare manifestation of systemic amyloidosis. However, whether skeletal muscle involvement is underestimated and whether such deposition guarantees clinical and pathological myopathic features remain to be investigated. METHODS: We retrospectively reviewed patients with systemic amyloidosis, in whom skeletal muscle biopsies were performed at our centre between January 2018 and June 2023. In total, 28 patients with suspected systemic amyloidosis were included. Among these, 21 presented with cardiomyopathy but lacked myopathic symptoms. The clinical and pathological data of these patients were further analysed. The amyloid type was confirmed by immunohistochemistry. RESULTS: Twenty-eight patients with suspected systemic amyloidosis underwent muscle biopsy. Amyloid deposition in the skeletal muscle was confirmed in 24 patients, including 22 with light-chain amyloidosis (AL) and two with transthyretin amyloidosis (ATTR). Among the 24 patients, seven presented with muscle weakness and decreased muscle strength (Group 1, symptomatic myopathy), whereas the remaining 17 exhibited normal muscle strength (Group 2, asymptomatic myopathy). Group 1 included four patients with AL-λ, one with AL-κ and two with ATTR. Group 2 included 15 patients with AL-λ and two patients with AL-κ. In Group 1, six patients exhibited neuropathy, whereas only one patient in Group 2 presented with subclinical neuropathy on nerve conduction studies. Amyloid deposition in the interstitium was the most obvious change, observed in all 24 patients. Neuropathic changes, including denervation atrophy and muscle fibre grouping, were also common. Except for type 2 fibre atrophy, the other myopathic changes were mild and nonspecific. No sarcolemmal disruption was observed. Immunohistochemical analysis revealed marked positivity for MAC and MHC1 expression in the regions with amyloid deposits. Clinicopathological analysis revealed no significant differences in the extent of muscular amyloid deposition between the two groups. Nevertheless, patients in Group 1 displayed more pronounced neurogenic atrophy on skeletal muscle biopsies. CONCLUSIONS: Our study indicates that amyloid deposition in skeletal muscle is commonly observed but rarely causes symptomatic myopathy in systemic amyloidosis.


Asunto(s)
Músculo Esquelético , Enfermedades Musculares , Humanos , Masculino , Músculo Esquelético/patología , Músculo Esquelético/metabolismo , Femenino , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Enfermedades Musculares/patología , Enfermedades Musculares/metabolismo , Amiloidosis/patología , Amiloidosis/complicaciones , Amiloidosis/metabolismo , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/patología , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/complicaciones , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/metabolismo , Anciano de 80 o más Años , Adulto , Biopsia
2.
Sheng Wu Gong Cheng Xue Bao ; 40(7): 2178-2194, 2024 Jul 25.
Artículo en Chino | MEDLINE | ID: mdl-39044583

RESUMEN

This study aims to explore the functions and mechanisms of testicular descent in Apodemus agrarius, and analyze the changes in genes and metabolite levels in this process. Illumina NovaSeq and liquid chromatography-mass spectrometry were used for the transcriptomic analysis and metabolomic analysis, respectively, of the normal and descending testis of A. agrarius. Gene ontology (GO) enrichment of the transcriptomic results revealed 240 differentially expressed genes (DEGs), such as Spesp1, Izumo1, Hyal5, and Fabp9. Kyoto encyclopedia of genes and genomes (KEGG) enrichment showed 52 DEGs, including Pcyt1, Pla2g4e, Gpd1l, and Lypla3. The qRT-PCR results were consistent with the transcriptomic results in terms of the expression patterns of six randomly selected genes in the normal and descending testis. The metabolomic results revealed 28 differential metabolites associated with the testicular function, including 3-dehydroquinic acid, α-linolenic acid, dihydroxyacetone phosphate, and fructose 1,6-bisphosphate. The conjoint analysis showcased that glycerophospholipid metabolism, α-linolenic acid metabolism, and arachidonic acid metabolism may be the key metabolic pathways regulating testicular descent in A. agrarius. This study will help to understand the mechanism of testicular descent and lay a theoretical foundation for exploring the mechanisms of the population changes of A. agrarius and developing laboratory animal resources.


Asunto(s)
Metabolómica , Murinae , Testículo , Transcriptoma , Masculino , Animales , Testículo/metabolismo , Testículo/crecimiento & desarrollo , Murinae/genética , Murinae/metabolismo , Perfilación de la Expresión Génica , Ácido alfa-Linolénico/metabolismo , Ácido Araquidónico/metabolismo , Ontología de Genes , Glicerofosfolípidos/metabolismo
3.
Adv Healthc Mater ; : e2401635, 2024 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-39054611

RESUMEN

In situ vaccination is an attractive type of cancer immunotherapy, and methods of persistently dispersing immune agonists throughout the entire tumor are crucial for maximizing their therapeutic efficacy. Based on the probiotics usually used for dietary supplements, an immunomodulator-boosted Lactococcus lactis (IBL) strategy is developed to enhance the effectiveness of in situ vaccination with the immunomodulators. The intratumoral delivery of OX40 agonist and resiquimod-modified Lactococcus lactis (OR@Lac) facilitates local retention and persistent dispersion of immunomodulators, and dramatically modulates the key components of anti-tumor immune response. This novel vaccine activated dendritic cells and cytotoxic T lymphocytes in the tumor and tumor-draining lymph nodes, and ultimately significantly inhibited tumor growth and prolonged the survival rate of tumor-bearing mice. The combination of OR@Lac and ibrutinib, a myeloid-derived suppressor cell inhibitor, significantly alleviated or even completely inhibited tumor growth in tumor-bearing mice. In conclusion, IBL is a promising in situ tumor vaccine approach for clinical application and provides an inspiration for the delivery of other drugs.

5.
Stem Cell Rev Rep ; 2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-39023738

RESUMEN

The cerebellum has historically been primarily associated with the regulation of precise motor functions. However, recent findings suggest that it also plays a pivotal role in the development of advanced cognitive functions, including learning, memory, and emotion regulation. Pathological changes in the cerebellum, whether congenital hereditary or acquired degenerative, can result in a diverse spectrum of disorders, ranging from genetic spinocerebellar ataxias to psychiatric conditions such as autism, and schizophrenia. While studies in animal models have significantly contributed to our understanding of the genetic networks governing cerebellar development, it is important to note that the human cerebellum follows a protracted developmental timeline compared to the neocortex. Consequently, employing animal models to uncover human-specific molecular events in cerebellar development presents significant challenges. The emergence of human induced pluripotent stem cells (hiPSCs) has provided an invaluable tool for creating human-based culture systems, enabling the modeling and analysis of cerebellar physiology and pathology. hiPSCs and their differentiated progenies can be derived from patients with specific disorders or carrying distinct genetic variants. Importantly, they preserve the unique genetic signatures of the individuals from whom they originate, allowing for the elucidation of human-specific molecular and cellular processes involved in cerebellar development and related disorders. This review focuses on the technical advancements in the utilization of hiPSCs for the generation of both 2D cerebellar neuronal cells and 3D cerebellar organoids.

6.
Age Ageing ; 53(7)2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-39041735

RESUMEN

BACKGROUND: Poor cardiovascular health (CVH) and physical frailty were reported to increase mortality risk, but their joint effects have not been fully elucidated. OBJECTIVES: We aimed to explore the separate and joint effects of CVH and frailty on mortality based on two perspectives of Life's Essential 8 (LE8) and Framingham Risk Score (FRS). METHODS: 21 062 participants in the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2018 were involved in this study. CVH was evaluated by the LE8 and FRS, and categorized into low, moderate and high CVH groups. Cox proportional hazard models were applied to estimate the separate and joint associations of CVH and frailty index (FI) with all-cause, cardiovascular disease (CVD) and cancer mortality. RESULTS: Over a median follow-up period of 87 months (95% CI: 86.0-88.0), 2036 deaths occurred. The separate linear dose-response relationships between CVH, frailty and mortality were observed (nonlinear P > .05). The combination of low CVH/frailty was negatively associated with all-cause mortality [hazard ratio (HR) and 95%CI: low LE8*FI, 5.30 (3.74, 7.52); high FRS*FI, 4.34 (3.20, 5.88)], CVD mortality [low LE8*FI, 6.57 (3.54, 12.22); high FRS*FI, 7.29 (3.92, 13.55)] and cancer mortality [low LE8*FI, 1.99 (1.14, 3.25); high FRS*FI, 2.32 (1.30, 4.15)], with high CVH/fit group as reference. Further stratified analyses showed that the combined burden of mortality from frailty and low CVH was greater among the young and females. CONCLUSIONS: Low CVH and frailty were independently and jointly correlated with greater risk of all-cause, CVD and cancer deaths, especially among the young and females.


Asunto(s)
Enfermedades Cardiovasculares , Causas de Muerte , Fragilidad , Encuestas Nutricionales , Humanos , Masculino , Femenino , Enfermedades Cardiovasculares/mortalidad , Fragilidad/mortalidad , Fragilidad/diagnóstico , Estudios Prospectivos , Persona de Mediana Edad , Anciano , Factores de Riesgo , Neoplasias/mortalidad , Medición de Riesgo , Modelos de Riesgos Proporcionales , Adulto , Estados Unidos/epidemiología , Anciano Frágil/estadística & datos numéricos
7.
Food Res Int ; 190: 114546, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38945559

RESUMEN

The thermal treatment carried out in the processing of apple products is very likely to induce Maillard reaction to produce furfurals, which have raised toxicological concerns. This study aimed to elucidate the formation of furfural compounds in apple products treated with pasteurization and high pressure processing (HPP). The method for simultaneous determination of five furfural compounds including 5-hydroxymethyl-2-furfural (5-HMF), furfural (F), 4-hydroxy-2,5-dimethyl-3(2H)-furanone (HDMF), 2-acetylfuran (FMC), and 5-Methyl-2-furfural (MF) using high performance liquid chromatography equipped with diode array detector (HPLC-DAD) was successfully developed and validated. All five furfurals exhibited an increasing trend after the pasteurization treatment of apple clear juice, cloudy juice, and puree. 5-HMF, F, FMC, and MF were increased significantly during the precooking of apple puree. Whereas there was no significant change in the furfurals formation after apple products treated with high pressure processing (HPP) with 300 MPa and 15 min. Based on the variation of the fructose, glucose and sucrose detected in apple products after thermal treatment, it revealed that the saccharides and thermal treatment have great effect on the furfural compounds formation. The commercial fruit juice samples with different treatments and fruit puree samples treated with pasteurization were also analyzed. Five furfurals were detected more frequently in the fruit juice samples treated with pasteurization or ultra-high temperature instantaneous sterilization (UHT) than those treated with HPP. 5-HMF and FMC were detected in all fruit puree samples treated with pasteurization, followed by F, MF, and HDMF with the detection rate of 79.31 %, 72.41 %, and 51.72 %. The results could provide a reference for risk assessment of furfural compounds and dietary guidance of fruit products for human, especially for infants and young children. Moreover, moderate HPP treatment with 300 MPa and 15 min would be a worthwhile alternative processing technology in the fruit juice and puree production to reduce the formation of furfural compounds.


Asunto(s)
Manipulación de Alimentos , Jugos de Frutas y Vegetales , Furaldehído , Malus , Pasteurización , Presión , Malus/química , Furaldehído/análisis , Furaldehído/análogos & derivados , Cromatografía Líquida de Alta Presión , Jugos de Frutas y Vegetales/análisis , Manipulación de Alimentos/métodos , Reacción de Maillard , Frutas/química , Furanos/análisis
8.
Women Health ; 64(5): 440-449, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38755523

RESUMEN

Female-specific reproductive factors might contribute to increased risk of cardiovascular disease, and the American Heart Association (AHA) recently proposed Life's Essential 8 (LE8) score to quantify cardiovascular health (CVH). The study aimed to examine the relationships between reproductive factors and the LE8 score among post-menopause women in the United States. We enrolled 3223 post-menopause women from National Health and Nutrition Examination Survey (NHANES). CVH groups based on LE8 score were low (0-49), moderate (50-79), and high good CVH levels (80-100). Multivariate ordinal logistic regressions were applied to estimate the associations between reproductive factors and the LE8 score. In multivariate model, early menarche (OR: 0.69, 95 percent CI: 0.51-0.93) and early menopause (OR: 0.57, 95 percent CI: 0.43-0.77) were associated with LE8 score compared with normal menarche and menopause; Meanwhile, ages at menarche and menopause were positively correlated with LE8 score. The number of pregnancies and full-term pregnancies were negatively associated with LE8 (OR for per pregnancy increase and 95 percent CI, 0.93 (0.88, 0.98), 0.93 (0.87, 0.99), separately). Overall, natural menopausal women with early age at menarche and menopause, and a higher number of pregnancies may have a high risk of lower CVH, and need to focus on their CVH.


Asunto(s)
Enfermedades Cardiovasculares , Menarquia , Menopausia , Encuestas Nutricionales , Posmenopausia , Humanos , Femenino , Persona de Mediana Edad , Enfermedades Cardiovasculares/epidemiología , Posmenopausia/fisiología , Estados Unidos/epidemiología , Menopausia/fisiología , Factores de Riesgo , Anciano , Estudios Transversales , Historia Reproductiva , Embarazo , Modelos Logísticos , Factores de Edad
9.
Stem Cell Res ; 77: 103435, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38733812

RESUMEN

We used a non-integrated reprogramming approach to establish a human induced pluripotent stem cell (hiPSC) line (INNDSUi004-A) from the skin fibroblasts of a 13-year-old female individual with Congenital Nemaline Myopath. The cells obtained have typical characteristics of embryonic stem cells, show expression of specific pluripotency markers, and can differentiate into three germ layers in vitro. This iPSC cell line has the genetic information of the patient and is a good model for studying disease mechanisms and developing novel therapies.


Asunto(s)
Diferenciación Celular , Células Madre Pluripotentes Inducidas , Miopatías Nemalínicas , Células Madre Pluripotentes Inducidas/metabolismo , Humanos , Miopatías Nemalínicas/patología , Miopatías Nemalínicas/genética , Femenino , Línea Celular , Adolescente , Fibroblastos/metabolismo , Reprogramación Celular
10.
Biomaterials ; 309: 122607, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38759487

RESUMEN

The use of CAR-T cells in treating solid tumors frequently faces significant challenges, mainly due to the heterogeneity of tumor antigens. This study assessed the efficacy of an acidity-targeting transition-aided universal chimeric antigen receptor T (ATT-CAR-T) cell strategy, which is facilitated by an acidity-targeted transition. Specifically, the EGFRvIII peptide was attached to the N-terminus of a pH-low insertion peptide. Triggered by the acidic conditions of the tumor microenvironment, this peptide alters its structure and selectively integrates into the membrane of solid tumor cells. The acidity-targeted transition component effectively relocated the EGFRvIII peptide across various tumor cell membranes; thus, allowing the direct destruction of these cells by EGFRvIII-specific CAR-T cells. This method was efficient even when endogenous antigens were absent. In vivo tests showed marked antigen modification within the acidic tumor microenvironment using this component. Integrating this component with CAR-T cell therapy showed high effectiveness in combating solid tumors. These results highlight the capability of ATT-CAR-T cell therapy to address the challenges presented by tumor heterogeneity and expand the utility of CAR-T cell therapy in the treatment of solid tumors.


Asunto(s)
Inmunoterapia Adoptiva , Neoplasias , Receptores Quiméricos de Antígenos , Microambiente Tumoral , Receptores Quiméricos de Antígenos/inmunología , Humanos , Animales , Línea Celular Tumoral , Concentración de Iones de Hidrógeno , Inmunoterapia Adoptiva/métodos , Neoplasias/terapia , Neoplasias/inmunología , Ratones , Receptores ErbB/metabolismo , Linfocitos T/inmunología , Femenino
11.
Shock ; 62(1): 63-68, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38661179

RESUMEN

ABSTRACT: Objective: In this study, our aim was to examine the effects of levosimendan on diaphragmatic dysfunction in patients with sepsis, as well as assess its impact on respiratory muscle contractility and the outcome of weaning. Methods: This was a single-blind, randomized, controlled trial. Patients with diaphragmatic dysfunction and failure of spontaneous breathing trials (SBTs) were randomly and equally assigned to the experimental and control groups. The experimental group received levosimendan at a loading dose of 6 µg/kg for 10 min, followed by a continuous infusion at 0.2 µg/kg/min. The control group received an equivalent dose of a placebo. The preadministration and postadministration respiratory mechanics parameters of the patients were recorded. Evaluation of the effect of levosimendan on patients with sepsis-induced diaphragm dysfunction comprised arterial blood gas analysis as well as ultrasound measurements of diaphragm excursion (DE), diaphragm thickness (DT), diaphragm thickening fraction (TFdi), and diaphragm-rapid shallow breathing index (D-RSBI). Results: Forty-four patients were enrolled in the study. We found that postadministration of levosimendan, the patients' tidal volume (GCSMV) increased, whereas the D-RSBI decreased, and the partial pressure of carbon dioxide (PACO 2 ) decreased when compared to the preadministration levels. Additionally, following levosimendan administration, patients showed increased DE and pressure support (PS) when compared to before administration (1.14 ± 0.177 vs. 1.22 ± 0.170 cm and 0.248 ± 0.03 vs. 0.284 ± 0.06, respectively) and decreased D-RSBI (22.76 ± 6.14 vs. 20.06 ± 6.04, respectively), all of which were statistically significant ( P < 0.05). In contrast, in the control group of patients, there were no statistically significant differences in the postadministration levels of DE, TFdi, and D-RSBI as compared to the preadministration period ( P > 0.05). Furthermore, in terms of weaning outcomes, we did not find any statistically significant difference in the number of patients in the two groups who eventually underwent weaning ( P = 0.545). Conclusion: In this study, we found that levosimendan enhanced diaphragm contractile function. However, further investigations are required to explore its effect on weaning outcomes in patients undergoing mechanical ventilation.


Asunto(s)
Diafragma , Hidrazonas , Piridazinas , Sepsis , Simendán , Humanos , Simendán/uso terapéutico , Sepsis/tratamiento farmacológico , Sepsis/fisiopatología , Diafragma/efectos de los fármacos , Diafragma/fisiopatología , Masculino , Femenino , Persona de Mediana Edad , Piridazinas/uso terapéutico , Hidrazonas/uso terapéutico , Anciano , Método Simple Ciego , Adulto , Análisis de los Gases de la Sangre
12.
World J Stem Cells ; 16(2): 137-150, 2024 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-38455095

RESUMEN

Blood vessels constitute a closed pipe system distributed throughout the body, transporting blood from the heart to other organs and delivering metabolic waste products back to the lungs and kidneys. Changes in blood vessels are related to many disorders like stroke, myocardial infarction, aneurysm, and diabetes, which are important causes of death worldwide. Translational research for new approaches to disease modeling and effective treatment is needed due to the huge socio-economic burden on healthcare systems. Although mice or rats have been widely used, applying data from animal studies to human-specific vascular physiology and pathology is difficult. The rise of induced pluripotent stem cells (iPSCs) provides a reliable in vitro resource for disease modeling, regenerative medicine, and drug discovery because they carry all human genetic information and have the ability to directionally differentiate into any type of human cells. This review summarizes the latest progress from the establishment of iPSCs, the strategies for differentiating iPSCs into vascular cells, and the in vivo transplantation of these vascular derivatives. It also introduces the application of these technologies in disease modeling, drug screening, and regenerative medicine. Additionally, the application of high-tech tools, such as omics analysis and high-throughput sequencing, in this field is reviewed.

13.
Heliyon ; 10(5): e27231, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38486779

RESUMEN

Catalpa bungei 'Jinsi', a cultivar of C. bungei C. A. Mey., is valued for its heartwood with good overall mechanical properties, naturally durable and golden-yellow color. Little is known about heartwood formation in C. bungei 'Jinsi' trees. The behavior of starch, water, and nuclei was studied in the xylem tissue of C. bungei 'Jinsi' concerning aging in ray parenchyma cells. Blocks containing heartwood, golden zone, transition zone, and sapwood were collected from the stems of six C. bungei 'Jinsi' trees. The moisture content of the blocks was measured by oven drying. Changes in starch and nuclei in ray parenchyma were investigated in radial profiles from sapwood to heartwood blocks using microscopy and various staining techniques. The nuclear size and starch content gradually decreased to heartwood. While the horizontal distribution of moisture content of C. bungei 'Jinsi' was very varied, with the heartwood and golden zone being lower than sapwood but slightly higher than the transition zone. Starch grains were rare, but nuclei were still present in some ray parenchyma cells in the heartwood and golden zone. The nuclei showed irregular shape and elongation before disintegration. These results suggest that the most apparent change occurs in the transition zone, the critical location involved in forming C. bungei 'Jinsi' heartwood. Water and starch appear to be actively engaged in heartwood formation. The loss of function of ray parenchyma cells results from heartwood formation.

14.
Stem Cell Res ; 77: 103386, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38484449

RESUMEN

We obtained skin fibroblasts from a 34-year-old healthy woman and established a human induced pluripotent stem cell (hiPSC) line (INDSUi005-A) using a non-integrated reprogramming approach. The obtained cells have typical characteristics of embryonic stem cells, can express specific pluripotency markers and have the ability to differentiate into three germ layers in vitro. This iPSC cell line can be used as an in vitro model for studying disease mechanisms and developing novel therapies.


Asunto(s)
Diferenciación Celular , Células Madre Pluripotentes Inducidas , Células Madre Pluripotentes Inducidas/citología , Células Madre Pluripotentes Inducidas/metabolismo , Humanos , Femenino , Adulto , Línea Celular , Fibroblastos/citología , Fibroblastos/metabolismo , Pueblo Asiatico , Reprogramación Celular , Pueblos del Este de Asia
15.
Transl Oncol ; 41: 101870, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38262108

RESUMEN

Low expression levels of breast cancer metastasis suppressor 1 like (BRMS1L) have been associated with the growth of cancer cells. However, the mechanisms underlying the role of BRMS1L as an antitumour transcription factor in the progression of NSCLC have not been explored. Herein, we reveal that BRMS1L plays a key role as a tumour suppressor in inhibiting NSCLC proliferation and metastasis. Mechanistically, BRMS1L overexpression results in the downregulation of glutathione peroxidase 2 (GPX2) expression and consequently causes abnormal glutathione metabolism and increased levels of reactive oxygen species (ROS) in cells, inducing oxidative stress injury and apoptosis. Furthermore, overexpression of GPX2 enhances the growth advantage and oxidative stress repair conferred by knockdown of BRMS1L. Importantly, we show that low expression of BRMS1L in NSCLC cells causes relatively high levels of antioxidant accumulation to maintain cell redox balance and renders cancer cells more sensitive to treatment with piperlongumine as an ROS inducer both in vitro and in vivo. These findings offer new insights into the role of BRMS1L as a transcriptional repressor in NSCLC and suggest that the BRMS1L expression level may be a potential biomarker for predicting the therapeutic response to small molecule ROS inducers, providing new ideas for targeted therapy.

16.
J Biol Eng ; 18(1): 7, 2024 Jan 16.
Artículo en Inglés | MEDLINE | ID: mdl-38229139

RESUMEN

BACKGROUND: Retinal pigment epithelium (RPE) cell therapy is a promising way to treat many retinal diseases. However, obtaining transplantable RPE cells is time-consuming and less effective. This study aimed to develop novel strategies for generating engineered RPE patches with physiological characteristics. RESULTS: Our findings revealed that RPE cells derived from human induced pluripotent stem cells (hiPSCs) successfully self-assembled into spheroids. The RPE spheroids treated with Y27632 and Repsox had increased expression of epithelial markers and RPE-specific genes, along with improved cell viability and barrier function. Transcriptome analysis indicated enhanced cell adhesion and extracellular matrix (ECM) organization in RPE spheroids. These RPE spheroids could be seeded and bioprinted on collagen vitrigel (CV) membranes to construct engineered RPE sheets. Circular RPE patches, obtained by trephining a specific section of the RPE sheet, exhibited abundant microvilli and pigment particles, as well as reduced proliferative capacity and enhanced maturation. CONCLUSIONS: Our study suggests that the supplementation of small molecules and 3D spheroid culture, as well as the bioprinting technique, can be effective methods to promote RPE cultivation and construct engineered RPE sheets, which may support future clinical RPE cell therapy and the development of RPE models for research applications.

17.
Food Res Int ; 177: 113894, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38225142

RESUMEN

The residue behaviors of carbendazim, thiamethoxam, imidacloprid, acetamiprid, prochloraz, and difenoconazole during the production and accelerated storage of apple clear and cloudy juice was systemically evaluated. The pesticides were determined by liquid chromatography-mass spectrometry (LC-MS/MS) after each processing step and at different storage times. The results indicated that the different processing steps in the apple clear and cloudy juices production have different effects on the reduction of pesticide residues. The pre-processing steps including washing and pressing reduced the pesticide residues significantly by 36.8 % to 67.9 % and 32.9 % to 89.8 %, respectively, mainly due to the water solubility and log Kow of pesticides. The enzymation step in clear juice production slightly reduced six pesticide residues from 1.9 % to 31.6 %, and the filtration step after clarification and purification decreased the pesticide residues from 14.0 % to 87.5 % with no significance, while prochloraz was not detected. The centrifugation step in cloudy juice production reduced the pesticide residues from 6.3 % to 88.9 %. The pasteurization step in clear and cloudy juice production lowered the pesticide residues slightly on account of the short heating time of 30 s. The accelerated storage of clear and cloudy juices was effective in the reduction of pesticide residue levels. The processing factors (PFs) in the whole process of clear and cloudy juice production were equal to or lower than 0.2, especially for prochloraz and difenoconazole, illustrating that apple juice production could decrease the pesticide residues greatly. The results will provide important references to predict the levels of pesticide residues in apple juice during processing and storage. Meanwhile, the PFs identified in the study could be helpful in the risk assessment of pesticides in apple juice.


Asunto(s)
Malus , Residuos de Plaguicidas , Plaguicidas , Malus/química , Plaguicidas/análisis , Residuos de Plaguicidas/análisis , Cromatografía Liquida , Manipulación de Alimentos/métodos , Espectrometría de Masas en Tándem , Frutas/química
18.
Sci Total Environ ; 916: 169999, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38242471

RESUMEN

The use of taste agents to regulate the grazing behavior of livestock is a new attempt in pasture management, but the effects on grassland plant communities are not clear at present. Therefore, the following scientific questions need to be addressed: (1) how do different taste agents affected plant community structure by changing feed intake? (2) What was the mechanism of this effect? We proposed the following hypotheses: (1) Salt and sweetener increased feed intake of livestock and decreased the biomass of plant community, while bitters did the opposite. (2) Taste agents can regulate the relationship between plant species, and different taste agents can enhance or weaken the competitiveness of the different plants. In order to test the hypothesis, a grazing experiment with yaks was conducted in the alpine meadows of the Tibetan Plateau. Denatonium benzoate (Bitterant), NaCl (Salt), and sodium cyclamate (Sweetener) were sprayed onto the meadows twice a year, along with a control treatment of tap water. The results showed that (1) Salt increased the feed intake of yak significantly; bitterant decreased the feed intake of livestock and increased the biomass of plant community. (2) Salt increased the Pielou index of the plant community significantly. (3) The stability of plant community ranking from high to low is as follows: Control > Bitterant > Sweetener > Salt. (4) Bitterant and salt improved grazing tolerance of grassland and salt reduced the edibility of grassland. (5) The use of taste agents reduced the correlation between dominant species and led to the fragmentation of the relationship chain. The results of this study will provide a theoretical basis for using taste agents to regulate the community, species biodiversity management, restoration of degraded grassland, promoting utilization of grassland though controlling livestock selectivity.


Asunto(s)
Pradera , Gusto , Animales , Bovinos , Agentes Aversivos , Suelo/química , Plantas , Ganado , Cloruro de Sodio , Edulcorantes , Tibet
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