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1.
Front Immunol ; 15: 1400177, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38953027

RESUMEN

Background: Chimeric antigen receptor T (CAR-T) cell therapies have achieved remarkable success in the treatment of hematological tumors. However, given the distinct features of solid tumors, particularly heterogeneity, metabolic aggressiveness, and fewer immune cells in tumor microenvironment (TME), the practical utility of CAR-T cells for solid tumors remains as a challenging issue. Meanwhile, although anti-PD-1 monoclonal antibody (mAb) has shown clinical efficacy, most mAbs also show limited clinical benefits for solid tumors due mainly to the issues associated with the lack of immune cells in TME. Thus, the infiltration of targeted immunological active cells into TME could generate synergistic efficacy for mAbs. Methods: We present a combinational strategy for solid tumor treatment, which combines armored-T cells to express Fc-gamma receptor I (FcγRI) fragment on the surfaces for targeting various tumors with therapeutically useful mAbs. Choosing CD20 and HER-2 as the targets, we characterized the in vitro and in vivo efficacy and latent mechanism of the combination drug by using flow cytometry, ELISA and other methods. Results: The combination and preprocessing of armored T-cells with corresponding antibody of Rituximab and Pertuzumab exerted profound anti-tumor effects, which is demonstrated to be mediated by synergistically produced antibody-dependent cellular cytotoxicity (ADCC) effects. Meanwhile, mAb was able to carry armored-T cell by preprocessing for the infiltration to TME in cell derived xenograft (CDX) model. Conclusions: This combination strategy showed a significant increase of safety profiles from the reduction of antibody doses. More importantly, the present strategy could be a versatile tool for a broad spectrum of cancer treatment, with a simple pairing of engineered T cells and a conventional antibody.


Asunto(s)
Neoplasias , Receptores de IgG , Linfocitos T , Microambiente Tumoral , Receptores de IgG/inmunología , Receptores de IgG/metabolismo , Humanos , Animales , Ratones , Neoplasias/inmunología , Neoplasias/terapia , Neoplasias/tratamiento farmacológico , Linfocitos T/inmunología , Microambiente Tumoral/inmunología , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales/inmunología , Línea Celular Tumoral , Ensayos Antitumor por Modelo de Xenoinjerto , Inmunoterapia Adoptiva/métodos , Receptor ErbB-2/inmunología , Receptor ErbB-2/antagonistas & inhibidores , Antineoplásicos Inmunológicos/farmacología , Antineoplásicos Inmunológicos/uso terapéutico , Receptores Quiméricos de Antígenos/inmunología , Receptores Quiméricos de Antígenos/genética , Femenino , Antígenos CD20/inmunología
2.
aBIOTECH ; 5(2): 202-208, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38974859

RESUMEN

CRISPR/Cas9, presently the most widely used genome editing technology, has provided great potential for functional studies and plant breeding. However, the strict requirement for a protospacer adjacent motif (PAM) has hindered the application of the CRISPR/Cas9 system because the number of targetable genomic sites is limited. Recently, the engineered variants Cas9-NG, SpG, and SpRY, which recognize non-canonical PAMs, have been successfully tested in plants (mainly in rice, a monocot). In this study, we evaluated the targeted mutagenesis capabilities of these Cas9 variants in two important Brassica vegetables, Chinese cabbage (Brassica rapa spp. pekinensis) and cabbage (Brassica oleracea var. capitata). Both Cas9-NG and SpG induced efficient mutagenesis at NGN PAMs, while SpG outperformed Cas9-NG at NGC and NGT PAMs. SpRY achieved efficient editing at almost all PAMs (NRN > NYN), albeit with some self-targeting activity at transfer (T)-DNA sequences. And SpRY-induced mutants were detected in cabbage plants in a PAM-less fashion. Moreover, an adenine base editor was developed using SpRY and TadA8e deaminase that induced A-to-G conversions within target sites using non-canonical PAMs. Together, the toolboxes developed here induced successful genome editing in Chinese cabbage and cabbage. Our work further expands the targeting scope of genome editing and paves the way for future basic research and genetic improvement in Brassica. Supplementary Information: The online version contains supplementary material available at 10.1007/s42994-024-00155-7.

3.
Chem Soc Rev ; 53(14): 7489-7530, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-38894663

RESUMEN

Global population growth and industrialization have exacerbated the nonrenewable energy crises and environmental issues, thereby stimulating an enormous demand for producing environmentally friendly materials. Typically, biomass-based aerogels (BAs), which are mainly composed of biomass materials, show great application prospects in various fields because of their exceptional properties such as biocompatibility, degradability, and renewability. To improve the performance of BAs to meet the usage requirements of different scenarios, a large number of innovative works in the past few decades have emphasized the importance of micro-structural design in regulating macroscopic functions. Inspired by the ubiquitous random or regularly arranged structures of materials in nature ranging from micro to meso and macro scales, constructing different microstructures often corresponds to completely different functions even with similar biomolecular compositions. This review focuses on the preparation process, design concepts, regulation methods, and the synergistic combination of chemical compositions and microstructures of BAs with different porous structures from the perspective of gel skeleton and pore structure. It not only comprehensively introduces the effect of various microstructures on the physical properties of BAs, but also analyzes their potential applications in the corresponding fields of thermal management, water treatment, atmospheric water harvesting, CO2 absorption, energy storage and conversion, electromagnetic interference (EMI) shielding, biological applications, etc. Finally, we provide our perspectives regarding the challenges and future opportunities of BAs. Overall, our goal is to provide researchers with a thorough understanding of the relationship between the microstructures and properties of BAs, supported by a comprehensive analysis of the available data.

4.
Sci Bull (Beijing) ; 2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-38853045

RESUMEN

Flexible light-emitting fibers and fabrics serve to bridge human-machine interactions. The desire for practical applications and the commercialization of flexible light-emitting fibers has accelerated structural progress and improvements. This review focuses on the structural design of light-emitting fibers and fabrics, starting with a summary of design principles, emission mechanisms, and structural evolution of coaxial structured light-emitting fibers. Subsequently, we explore recent advances in the helical structure design strategies that boost the mechanical sensitivity of light-emitting fibers. Following that, we analyze continuous preparation processes and the development of large-area intelligent light-emitting fabrics based on interwoven structures. Examples based on stiff and rigid inorganic-based light-emitting diodes integrated into flexible systems are also presented. Finally, we discuss the current challenges and future opportunities for light-emitting applications in the field of wearable and smart devices.

5.
Medicine (Baltimore) ; 103(23): e38392, 2024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-38847661

RESUMEN

There is a correlation between IBD and breast cancer according to previous observational studies. However, so far there is no evidence to support if there is a causal relationship between these 2 diseases. We acquired comprehensive Genome-Wide Association Study (GWAS) summary data on IBD (including ulcerative colitis [UC] and Crohn disease [CD]) as well as breast cancer of completely European descent from the IEU GWAS database. The estimation of bidirectional causality between IBD (including UC and CD) and breast cancer was achieved through the utilization of 2-sample Mendelian randomization (MR). The MR results were also assessed for any potential bias caused by heterogeneity and pleiotropy through sensitivity analyses. Our study found a bidirectional causal effect between IBD and breast cancer. Genetic susceptibility to IBD was associated with an increased risk of breast cancer (OR = 1.053, 95% CI: 1.016-1.090, P = .004). Similarly, the presence of breast cancer may increase the risk of IBD (OR = 1.111, 95% CI: 1.035-1.194, P = .004). Moreover, the bidirectional causal effect between IBD and breast cancer can be confirmed by another GWAS of IBD. Subtype analysis showed that CD was associated with breast cancer (OR = 1.050, 95% CI: 1.020-1.080, P < .001), but not UC and breast cancer. There was a suggestive association between breast cancer and UC (OR = 1.106, 95% CI: 1.011-1.209, P = .028), but not with CD. This study supports a bidirectional causal effect between IBD and breast cancer. There appear to be considerable differences in the specific associations of UC and CD with AD. Understanding that IBD including its specific subtypes and breast cancer constitute common risk factors can contribute to the clinical management of both diseases.


Asunto(s)
Neoplasias de la Mama , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Humanos , Análisis de la Aleatorización Mendeliana/métodos , Neoplasias de la Mama/genética , Neoplasias de la Mama/epidemiología , Femenino , Enfermedad de Crohn/genética , Enfermedad de Crohn/epidemiología , Enfermedades Inflamatorias del Intestino/genética , Colitis Ulcerosa/genética , Colitis Ulcerosa/epidemiología , Factores de Riesgo , Polimorfismo de Nucleótido Simple
6.
Carbohydr Polym ; 339: 122250, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-38823917

RESUMEN

Glycyrrhizae Radix et rhizome/licorice is a precious herb in traditional Chinese medicine (TCM). TCM's polysaccharides are medicinally active. But herbal polysaccharides pose some limitations for topical applications. Therefore, this study aimed to utilize licorice polysaccharide via mesoporous silica nanoparticles (MSN) for anti-acne efficacy in topical delivery. The polysaccharide (GGP) was extracted with a 10 % NaOH solution. Chemical characterization suggested that GGP possesses an Mw of 267.9 kDa, comprised primarily of Glc (54.1 %) and Ara (19.12 %), and probably 1,4-linked Glc as a backbone. Then, MSN and amino-functionalized MSN were synthesized, GGP entrapped, and coated with polydopamine (PDA) to produce nanoparticle cargo. The resulted product exhibited 76 % entrapment efficiency and an in vitro release of 89 % at pH 5, which is usually an acne-prone skin's pH. Moreover, it significantly increased Sebocytes' cellular uptake. GGP effectively acted as an anti-acne agent and preserved its efficacy in synthesized nanoparticles. In vivo, the results showed that a 20 % gel of MSN-NH2-GGP@PDA could mediate an inflammatory response via inhibiting pro-inflammatory cytokines and regulating anti-inflammatory cytokines. The MSN-NH2-GGP@PDA inhibited TLR2-activated-MAPK and NF-κB pathway triggered by heat-killed P. acnes. In conclusion, fabricated MSN entrapped GGP for biomimetic anti-acne efficacy in topical application.


Asunto(s)
Acné Vulgar , Glycyrrhiza , Nanopartículas , Polisacáridos , Dióxido de Silicio , Glycyrrhiza/química , Dióxido de Silicio/química , Polisacáridos/química , Polisacáridos/farmacología , Nanopartículas/química , Animales , Porosidad , Acné Vulgar/tratamiento farmacológico , Ratones , Administración Tópica , Humanos , Portadores de Fármacos/química , Liberación de Fármacos , Indoles , Polímeros
7.
Sci China Life Sci ; 2024 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-38926247

RESUMEN

Suppressor tRNAs are engineered or naturally occurring transfer RNA molecules that have shown promise in gene therapy for diseases caused by nonsense mutations, which result in premature termination codons (PTCs) in coding sequence, leading to truncated, often nonfunctional proteins. Suppressor tRNAs can recognize and pair with these PTCs, allowing the ribosome to continue translation and produce a full-length protein. This review introduces the mechanism and development of suppressor tRNAs, compares suppressor tRNAs with other readthrough therapies, discusses their potential for clinical therapy, limitations, and obstacles. We also summarize the applications of suppressor tRNAs in both in vitro and in vivo, offering new insights into the research and treatment of nonsense mutation diseases.

8.
Sci Total Environ ; 931: 172973, 2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38705294

RESUMEN

In this work, corn straw was used as raw material, Hummers method and activation were used to adjust the graphite structure in biochar, and preparing straw based biochar (H-BCS) with ultra-high specific surface area (3441.80 m2/g), highly total pore volume (1.9859 cm3/g), and further enhanced physicochemical properties. Compared with untreated straw biochar (BCS), the specific surface area and total pore volume of H-BCS were increased by 47.24 % and 55.85 %, respectively. H-BCS showed good removal ability in subsequent experiments by using chloramphenicol (CP), hexavalent chromium (Cr6+), and crystal violet (CV) as adsorption models. In addition, the adsorption capacities of H-BCS (CP: 1396.30 mg/g, Cr6+: 218.40 mg/g, and CV: 1246.24 mg/g) are not only higher than most adsorbents, even after undergoing 5 cycles of regeneration, its adsorption capacity remains above 80 %, indicating significant potential for practical applications. In addition, we also speculated and analyzed the conjecture about the "graphite-structure regulation" during the preparation process, and finally discussed the possible mechanism during the adsorption processes. We hope this work could provide a new strategy to solve the restriction of biochar performance by further exploring the regulation of graphite structure in carbon materials.


Asunto(s)
Carbón Orgánico , Grafito , Contaminantes Químicos del Agua , Carbón Orgánico/química , Grafito/química , Contaminantes Químicos del Agua/análisis , Contaminantes Químicos del Agua/química , Adsorción , Eliminación de Residuos Líquidos/métodos , Cromo/química , Contaminación del Agua/prevención & control , Zea mays/química , Purificación del Agua/métodos
9.
ACS Appl Mater Interfaces ; 16(21): 27794-27803, 2024 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-38748448

RESUMEN

The development of optical humidity detection has been of considerable interest in highly integrated wearable electronics and packaged equipment. However, improving their capacities for color recognition at ultralow humidity and response-recovery rate remains a significant challenge. Herein, we propose a type of hybrid water-harvesting channel to construct brand-new passive fluorescence humidity sensors (PFHSs). Specifically, the hybrid water-harvesting channels involve porous metal-organic frameworks and a hydrophilic poly(acrylic acid) network that can capture water vapors from the ambient environment even at ultralow humidity, into which polar-responsive aggregation-induced emission molecules are doped to impart humidity-sensitive luminescence colors. As a result, the PFHSs exhibit clearly defined fluorescence signals within 0-98% RH coupling with desirable performances such as a fast response rate, precise quantitative feedback, and durable reversibility. Given the flexible processability of this system, we further upgrade the porous structure via electrostatic spinning to furnish a kind of Nano-PFHSs, demonstrating an impressive response time (<100 ms). Finally, we validate the promising applications of these sensors in electronic humidity monitoring and successfully fabricate a portable and rapid humidity indicator card.

10.
Bioelectrochemistry ; 158: 108727, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38728815

RESUMEN

Herein, we demonstrate a simple, homogenous and label-free electrochemical biosensing system for sensitive nucleic acid detection based on target-responsive porous materials and nuclease-triggered target recycling amplification. The Fe(CN)63- reporter was firstly sealed into the pores of Fe3O4 nanoparticles by probe DNA. Target DNA recognition triggered the controllable release of Fe(CN)63- for the redox reaction with the electron mediator of methylene blue enriched in the dodecanethiol assembled electrode and thereby generating electrochemical signal. The exonuclease III (Exo III)-assisted target recycling and the catalytic redox recycling between Fe(CN)63- and methylene blue contributed for the enhanced signal response toward target recognition. The low detection limit toward target was obtained as 478 fM and 1.6 pM, respectively, by square wave voltammetry and cyclic voltammetry methods. It also possessed a well-discrimination ability toward mismatched strands and high tolerance to complex sample matrix. The coupling of bio-gated porous nanoparticles, nuclease-assisted target amplification and catalytic redox recycling afforded the sensing system with well-controllable signal responses, sensitive and selective DNA detection, and good stability, reusability and reproducibility. It thus opens a new avenue toward the development of simple but sensitive electrochemical biosensing platform.


Asunto(s)
Técnicas Biosensibles , ADN , Técnicas Electroquímicas , Límite de Detección , Oxidación-Reducción , Técnicas Biosensibles/métodos , ADN/química , Técnicas Electroquímicas/métodos , Catálisis , Exodesoxirribonucleasas/metabolismo , Exodesoxirribonucleasas/química , Azul de Metileno/química
11.
J Immunol Res ; 2024: 4722047, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38745751

RESUMEN

Hepatitis B virus (HBV) infection is a major global health issue and ranks among the top causes of liver cirrhosis and hepatocellular carcinoma. Although current antiviral medications, including nucleot(s)ide analogs and interferons, could inhibit the replication of HBV and alleviate the disease, HBV cannot be fully eradicated. The development of cellular and animal models for HBV infection plays an important role in exploring effective anti-HBV medicine. During the past decades, advancements in several cell culture systems, such as HepG2.2.15, HepAD38, HepaRG, hepatocyte-like cells, and primary human hepatocytes, have propelled the research in inhibiting HBV replication and expression and thus enriched our comprehension of the viral life cycle and enhancing antiviral drug evaluation efficacy. Mouse models, in particular, have emerged as the most extensively studied HBV animal models. Additionally, the present landscape of HBV therapeutics research now encompasses a comprehensive assessment of the virus's life cycle, targeting numerous facets and employing a variety of immunomodulatory approaches, including entry inhibitors, strategies aimed at cccDNA, RNA interference technologies, toll-like receptor agonists, and, notably, traditional Chinese medicine (TCM). This review describes the attributes and limitations of existing HBV model systems and surveys novel advancements in HBV treatment modalities, which will offer deeper insights toward discovering potentially efficacious pharmaceutical interventions.


Asunto(s)
Antivirales , Modelos Animales de Enfermedad , Virus de la Hepatitis B , Hepatitis B , Replicación Viral , Humanos , Animales , Virus de la Hepatitis B/fisiología , Virus de la Hepatitis B/efectos de los fármacos , Antivirales/uso terapéutico , Antivirales/farmacología , Hepatitis B/tratamiento farmacológico , Hepatitis B/virología , Hepatitis B/inmunología , Replicación Viral/efectos de los fármacos , Ratones , Hepatocitos/virología
12.
Angew Chem Int Ed Engl ; 63(29): e202403391, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-38717757

RESUMEN

Room temperature phosphorescence (RTP) materials have garnered significant attention owing to its distinctive optical characteristics and broad range of potential applications. However, the challenge remains in producing RTP materials with more simplicity, versatility, and practicality on a large scale, particularly in achieving chiral signals within a single system. Herein, we show that a straightforward and effective combination of wet spinning and twisting technique enables continuously fabricating RTP fibers with twisting-induced helical chirality. By leveraging the hydrogen bonding interactions between polyvinyl alcohol (PVA) and quinoline derivatives, along with the rigid microenvironment provided by PVA chains, typically, Q-NH2@PVA fiber demonstrates outstanding phosphorescent characteristics with RTP lifetime of 1.08 s and phosphorescence quantum yield of 24.6 %, and the improved tensile strength being 1.7 times than pure PVA fiber (172±5.82 vs 100±5.65 MPa). Impressively, the transformation from RTP to circularly polarized room temperature phosphorescence (CP-RTP) is readily achieved by imparting left- or right-hand helical structure through simply twisting, enabling large-scale production of chiral Q-NH2@PVA fiber with dissymmetry factor of 10-2. Besides, an array of displays and encryption patterns are crafted by weaving or seaming to exemplify the promising applications of these PVA-based fibers with outstanding adaptivity in cutting-edge anti-counterfeiting technology.

13.
Life Sci ; 349: 122714, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-38735366

RESUMEN

AIMS: Non-alcoholic fatty liver disease (NAFLD) has risen as a significant global public health issue, for which vertical sleeve gastrectomy (VSG) has become an effective treatment method. The study sought to elucidate the processes through which PIM1 mitigates the advancement of NAFLD. The Pro-viral integration site for Moloney murine leukemia virus 1 (PIM1) functions as a serine/threonine kinase. Bioinformatics analysis revealed that reduced PIM1 expression in NAFLD. METHODS: To further prove the role of PIM1 in NAFLD, an in-depth in vivo experiment was performed, in which male C57BL/6 mice were randomly grouped to receive a normal or high-fat diet for 24 weeks. They were operated or delivered the loaded adeno-associated virus which the PIM1 was overexpressed (AAV-PIM1). In an in vitro experiment, AML12 cells were treated with palmitic acid to induce hepatic steatosis. KEY FINDINGS: The results revealed that the VSG surgery and virus delivery of mice alleviated oxidative stress, and apoptosis in vivo. For AML12 cells, the levels of oxidative stress, apoptosis, and lipid metabolism were reduced via PIM1 upregulation. Moreover, ML385 treatment resulted in the downregulation of the NRF2/HO-1/NQO1 signaling cascade, indicating that PIM1 mitigates NAFLD by targeting this pathway. SIGNIFICANCE: PIM1 alleviated mice liver oxidative stress and NAFLD induced by high-fat diet by regulating the NRF2/HO-1/NQO1 signaling Pathway.


Asunto(s)
Hemo-Oxigenasa 1 , Ratones Endogámicos C57BL , NAD(P)H Deshidrogenasa (Quinona) , Factor 2 Relacionado con NF-E2 , Enfermedad del Hígado Graso no Alcohólico , Estrés Oxidativo , Proteínas Proto-Oncogénicas c-pim-1 , Animales , Proteínas Proto-Oncogénicas c-pim-1/metabolismo , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Masculino , Ratones , Factor 2 Relacionado con NF-E2/metabolismo , NAD(P)H Deshidrogenasa (Quinona)/metabolismo , NAD(P)H Deshidrogenasa (Quinona)/genética , Hemo-Oxigenasa 1/metabolismo , Dieta Alta en Grasa/efectos adversos , Hígado/metabolismo , Hígado/patología , Transducción de Señal , Apoptosis , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética
14.
Talanta ; 276: 126212, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-38723475

RESUMEN

As a popular nutritional enhancer, casein phosphopeptides (CPPs) have attracted growing attention in food industry. However, conventional methods for CPPs detection are usually less precise or requires expensive instruments. Herein, a nanozyme-based colorimetric method was developed to achieve the quantitative detection of CPPs in food samples. This method is based on a facilely fabricated peroxidase-like nanozyme (Fe@UiO-66), which combines the specific binding of CPPs, as well as the nanozyme-catalyzed colorimetric sensing that can be easily detected by spectrometer. The method displayed good quantitative ability toward CPPs with the linear range of 2-30 µg/mL, the low limit of detection of 0.267 µg/mL and limit of quantification of 1.335 µg/mL. We highlighted the specificity, anti-interference and practicability of this method, by investigating the performances toward food samples. Besides, a smartphone-based colorimetric sensing platform was also established, which is conducive to the portable detection. The developed nanozyme-based colorimetric sensing method provides a promising strategy for CPPs detection in food samples.


Asunto(s)
Caseínas , Colorimetría , Fosfopéptidos , Colorimetría/métodos , Caseínas/análisis , Caseínas/química , Fosfopéptidos/análisis , Análisis de los Alimentos/métodos , Límite de Detección , Estructuras Metalorgánicas/química , Animales
15.
Front Immunol ; 15: 1368275, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38562943

RESUMEN

Autoimmune encephalitis (AE) broadly refers to inflammation of the brain parenchyma mediated by autoimmune mechanisms. In most patients with AE, autoantibodies against neuronal cell surface antigens are produced by B-cells and induce neuronal dysfunction through various mechanisms, ultimately leading to disease progression. In recent years, B-cell targeted therapies, including monoclonal antibody (mAb) therapy and chimeric antigen receptor T-cell (CAR-T) therapy, have been widely used in autoimmune diseases. These therapies decrease autoantibody levels in patients and have shown favorable results. This review summarizes the mechanisms underlying these two B-cell targeted therapies and discusses their clinical applications and therapeutic potential in AE. Our research provides clinicians with more treatment options for AE patients whose conventional treatments are not effective.


Asunto(s)
Enfermedades Autoinmunes del Sistema Nervioso , Encefalitis , Enfermedad de Hashimoto , Humanos , Autoanticuerpos , Anticuerpos Monoclonales/uso terapéutico , Enfermedades Autoinmunes del Sistema Nervioso/tratamiento farmacológico
16.
STAR Protoc ; 5(2): 103019, 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38635394

RESUMEN

In vitro cell culture serves as an efficient system for studying animal cell behavior in a controlled setting. Here, we present a 3D culture model for forming ruminant adipose organoids using stromal vascular fraction cells. We describe steps for forming cell spheroids and growing them on a Matrigel-coated surface. We then detail procedures for inducing organoids to undergo angiogenesis and adipogenesis followed by capillary sprouting. This protocol can be utilized to study the interaction between blood vessels and adipocytes. For complete details on the use and execution of this protocol, please refer to Yu et al.1.


Asunto(s)
Tejido Adiposo , Organoides , Animales , Organoides/citología , Tejido Adiposo/citología , Células del Estroma/citología , Rumiantes , Técnicas de Cultivo de Célula/métodos , Neovascularización Fisiológica/fisiología , Adipogénesis/fisiología , Adipocitos/citología , Células Cultivadas
17.
Gen Physiol Biophys ; 43(2): 85-102, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38477602

RESUMEN

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent liver disease worldwide. Chronic activation of endoplasmic reticulum stress (ERS) in hepatocytes may promote the development of NAFLD, yet endoplasmic reticulum stress-related genes (ERSGs) have not been studied in NAFLD. Our aim is to study the relationship between ERSGs and the immune microenvironment of NAFLD patients and to construct predictive models. We screened 48 endoplasmic reticulum stress-related differentially expressed genes (ERSR-DEGs) using data from two GEO datasets and the GeneCards database. Enrichment analysis revealed that ERSR-DEGs are closely associated with immune-related pathways and functions. The immune infiltration profile of NAFLD was obtained by single sample gene set enrichment analysis (ssGSEA). There were significant differences in immune cell infiltration and immune function between NAFLD group and control group. Using 113 NAFLD samples, we explored two molecular clusters based on ERSR-DEGs. A five-gene SVM model was selected as the best machine learning model, and a nomogram based on five-gene SVM model showed good predictive efficiency. The mRNA expression levels of POR, PPP1R15A, FOS and FAS were significantly different between NAFLD mice and healthy mice. In conclusion, ERS is closely associated with the development of NAFLD. We established a promising and SVM-based predictive model to assess the risk of disease in patients with ERS subtypes and NAFLD.


Asunto(s)
Enfermedad del Hígado Graso no Alcohólico , Humanos , Ratones , Animales , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Estrés del Retículo Endoplásmico/genética , Hepatocitos
18.
Colloids Surf B Biointerfaces ; 235: 113774, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38309154

RESUMEN

This study presents the development of a sensitive and simple enhanced ratiometric fluorescence sensing platform in the consist of CdTe quantum dots (QDs), carbon dots (CDs), and hepatitis B core antibody labeled with horseradish peroxidase (HBcAb-HRP) for the visual analysis of H2O2 and glucose. The sulfur atoms in HBcAb-HRP have a strong affinity for Cd(II), which effectively enhances the fluorescence intensity of the CdTe QDs due to the generation of more radiative centers at the CdTe/Cd-SR complex. In the presence of H2O2, the Cd-S bonds are oxidized to form disulfide products and results in linear fluorescence quenching, while CDs maintain stable. Becasue glucose can be converted into H2O2 with the aid of glucose oxidase, this sensing platform can also be used for analyzing glucose. The detection limits for H2O2 and glucose are 2.9 µmol L-1 with RSD of 2.6% and 1.6 µmol L-1 with RSD of 2.4% respectively. In addition, under UV lamp irradiation, the orange-yellow CdTe QDs gradually quench with increasing H2O2 and glucose, while the blue CDs remain unchanged. A color change from orange-yellow to blue enables a visual semi-quantitative determination of H2O2 in commercial contact lens solution and glucose in human serum without any pretreatment. Thus, this CdTe QDs/CDs ratiometric sensing platform has significant potential for the rapid analysis of H2O2 and glucose in actual application.


Asunto(s)
Compuestos de Cadmio , Puntos Cuánticos , Humanos , Peróxido de Hidrógeno/química , Puntos Cuánticos/química , Glucosa/química , Carbono , Compuestos de Cadmio/química , Telurio/química , Anticuerpos contra la Hepatitis B , Peroxidasa de Rábano Silvestre/química , Colorantes Fluorescentes/química
19.
Toxicology ; 502: 153719, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-38181850

RESUMEN

Per- and polyfluoroalkyl substances (PFASs), a group of synthetic chemicals that were once widely used for industrial purposes and in consumer products, are widely found in the environment and in human blood due to their extraordinary resistance to degradation. Once inside the body, PFASs can activate nuclear receptors such as PPARα and CAR. The present study aimed to investigate the impact of perfluorooctanoic acid (PFOA) and perfluorodecanoic acid (PFDA) on liver structure and functions, as well as bile acid homeostasis in mice. A single administration of 0.1 mmole/kg of PFDA, not PFOA, elevated serum ALT and bilirubin levels and caused cholestasis in WT mice. PFDA increased total and various bile acid species in serum but decreased them in the liver. Furthermore, in mouse livers, PFDA, not PFOA, down-regulated mRNA expression of uptake transporters (Ntcp, Oatp1a1, 1a4, 1b2, and 2b1) but induced efflux transporters (Bcrp, Mdr2, and Mrp2-4). In addition, PFDA, not PFOA, decreased Cyp7a1, 7b1, 8b1, and 27a1 mRNA expression in mouse livers with concomitant hepatic accumulation of cholesterol. In contrast, in PPARα-null mice, PFDA did not increase serum ALT, bilirubin, or total bile acids, but produced prominent hepatosteatosis; and the observed PFDA-induced expression changes of transporters and Cyps in WT mice were largely attenuated or abolished. In CAR-null mice, the observed PFDA-induced bile acid alterations in WT mice were mostly sustained. These results indicate that, at the dose employed, PFDA has more negative effects than PFOA on liver function. PPARα appears to play a major role in mediating most of PFDA-induced effects, which were absent or attenuated in PPARα-null mice. Lack of PPARα, however, exacerbated hepatic steatosis. Our findings indicate separated roles of PPARα in mediating the adaptive responses to PFDA: protective against hepatosteatosis but exacerbating cholestasis.


Asunto(s)
Caprilatos , Colestasis , Ácidos Decanoicos , Fluorocarburos , Humanos , Ratones , Animales , Ácidos y Sales Biliares/metabolismo , PPAR alfa/genética , PPAR alfa/metabolismo , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2/metabolismo , Proteínas de Neoplasias , Hígado , Fluorocarburos/metabolismo , Ratones Noqueados , Bilirrubina/toxicidad , Bilirrubina/metabolismo , ARN Mensajero/metabolismo
20.
Bioresour Technol ; 395: 130325, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38228219

RESUMEN

Herein, three enzymes (cellulase, ß-glucosidase, and pectinase) with synergistic effects were co-immobilized on the Eudragit L-100, and the recovery of co-immobilized enzymes from solid substrates were achieved through the reversible and soluble property of the carrier. The optimization of enzyme ratio overcomed the problem of inappropriate enzyme activity ratio caused by different immobilization efficiencies among enzymes during the preparation process of co-immobilized enzymes. The co-immobilized enzymes were utilized to catalytically hydrolyze cellulose from corn straw into glucose, achieving a cellulose conversion rate of 74.45% under conditions optimized for their enzymatic characteristics and hydrolytic reaction conditions. As a result of the reversibility and solubility of the carrier, the co-immobilized enzymes were recovered from the solid substrate after five cycles, retaining 54.67% of the enzyme activity. The aim of this study is to investigate the potential of co-immobilizing multiple enzymes onto the Eudragit L-100 carrier for the synergistic degradation of straw cellulose.


Asunto(s)
Celulasa , Celulosa , Celulosa/metabolismo , Zea mays/metabolismo , Enzimas Inmovilizadas/metabolismo , Ácidos Polimetacrílicos , Celulasa/metabolismo , Hidrólisis
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