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1.
Materials (Basel) ; 17(9)2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38730953

RESUMEN

In this article, ABA triblock copolymer (tri-BCP) thermoplastic elastomers with poly(ethylene oxide) (PEO) middle block and polyzwitterionic poly(4-vinylpyridine) propane-1-sulfonate (PVPS) outer blocks were synthesized. The PVPS-b-PEO-b-PVPS tri-BCPs were doped with lithium bis-(trifluoromethane-sulfonyl) imide (LiTFSI) and used as solid polyelectrolytes (SPEs). The thermal properties and microphase separation behavior of the tri-BCP/LiTFSI hybrids were studied. Small-angle X-ray scattering (SAXS) results revealed that all tri-BCPs formed asymmetric lamellar structures in the range of PVPS volume fractions from 12.9% to 26.1%. The microphase separation strength was enhanced with increasing the PVPS fraction (fPVPS) but was weakened as the doping ratio increased, which affected the thermal properties of the hybrids, such as melting temperature and glass transition temperature, to some extent. As compared with the PEO/LiTFSI hybrids, the PVPS-b-PEO-b-PVPS/LiTFSI hybrids could achieve both higher modulus and higher ionic conductivity, which were attributed to the physical crosslinking and the assistance in dissociation of Li+ ions by the PVPS blocks, respectively. On the basis of excellent electrical and mechanical performances, the PVPS-b-PEO-b-PVPS/LiTFSI hybrids can potentially be used as solid electrolytes in lithium-ion batteries.

2.
Eur J Med Chem ; 272: 116477, 2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38733884

RESUMEN

The cellular-mesenchymal epithelial transition factor (c-Met) is a receptor tyrosine kinase (RTK) located on the 7q31 locus encoding the Met proto-oncogene and plays a critical role in regulating cell proliferation, metastasis, differentiation, and apoptosis through various signaling pathways. However, its aberrant activation and overexpression have been implicated in many human cancers. Therefore, c-Met is a promising target for cancer treatment. However, the anticancer effect of selective single-targeted drugs is limited due to the complexity of the signaling system and the involvement of different proteins and enzymes. After inhibiting one pathway, signal molecules can be transmitted through other pathways, resulting in poor efficacy of single-targeted drug therapy. Dual inhibitors that simultaneously block c-Met and another factor can significantly improve efficacy and overcome some of the shortcomings of single-target inhibitors, including drug resistance. In this review, We introduced c-Met kinase and the synergism between c-Met and other anti-tumor targets, then dual-target inhibitors based on c-Met for the treatment of cancers were summarized and their design concepts and structure-activity relationships (SARs) were discussed elaborately, providing a valuable insight for the further development of novel c-Met-based dual inhibitors.


Asunto(s)
Antineoplásicos , Neoplasias , Inhibidores de Proteínas Quinasas , Proto-Oncogenes Mas , Proteínas Proto-Oncogénicas c-met , Proteínas Proto-Oncogénicas c-met/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-met/metabolismo , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/química , Inhibidores de Proteínas Quinasas/síntesis química , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/uso terapéutico , Relación Estructura-Actividad , Estructura Molecular , Proliferación Celular/efectos de los fármacos , Animales
3.
Cell Biol Toxicol ; 40(1): 40, 2024 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-38797732

RESUMEN

MYBL1 is a strong transcriptional activator involved in the cell signaling. However, there is no systematic study on the role of MYBL1 in atherosclerosis. The aim of this study is to elucidate the role and mechanism of MYBL1 in atherosclerosis. GSE28829, GSE43292 and GSE41571 were downloaded from NCBI for differentially expressed analysis. The expression levels of MYBL1 in atherosclerotic plaque tissue and normal vessels were detected by qRT-PCR, Western blot and Immunohistochemistry. Transwell and CCK-8 were used to detect the migration and proliferation of HUVECs after silencing MYBL1. RNA-seq, Western blot, qRT-PCR, Luciferase reporter system, Immunofluorescence, Flow cytometry, ChIP and CO-IP were used to study the role and mechanism of MYBL1 in atherosclerosis. The microarray data of GSE28829, GSE43292, and GSE41571 were analyzed and intersected, and then MYBL1 were verified. MYBL1 was down-regulated in atherosclerotic plaque tissue. After silencing of MYBL1, HUVECs were damaged, and their migration and proliferation abilities were weakened. Overexpression of MYBL1 significantly enhanced the migration and proliferation of HUVECs. MYBL1 knockdown induced abnormal autophagy in HUVEC cells, suggesting that MYBL1 was involved in the regulation of HUVECs through autophagy. Mechanistic studies showed that MYBL1 knockdown inhibited autophagosome and lysosomal fusion in HUVECs by inhibiting PLEKHM1, thereby exacerbating atherosclerosis. Furthermore, MYBL1 was found to repress lipid accumulation in HUVECs after oxLDL treatment. MYBL1 knockdown in HUVECs was involved in atherosclerosis by inhibiting PLEKHM1-induced autophagy, which provided a novel target of therapy for atherosclerosis.


Asunto(s)
Aterosclerosis , Autofagia , Movimiento Celular , Proliferación Celular , Regulación hacia Abajo , Células Endoteliales de la Vena Umbilical Humana , Humanos , Aterosclerosis/metabolismo , Aterosclerosis/genética , Aterosclerosis/patología , Autofagia/genética , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Proliferación Celular/genética , Movimiento Celular/genética , Regulación hacia Abajo/genética , Glicoproteínas de Membrana/metabolismo , Glicoproteínas de Membrana/genética , Transactivadores/metabolismo , Transactivadores/genética , Placa Aterosclerótica/metabolismo , Placa Aterosclerótica/genética , Placa Aterosclerótica/patología , Animales
4.
World J Gastroenterol ; 30(9): 1108-1120, 2024 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-38577179

RESUMEN

BACKGROUND: Although chronic erosive gastritis (CEG) is common, its clinical characteristics have not been fully elucidated. The lack of consensus regarding its treatment has resulted in varied treatment regimens. AIM: To explore the clinical characteristics, treatment patterns, and short-term outcomes in CEG patients in China. METHODS: We recruited patients with chronic non-atrophic or mild-to-moderate atrophic gastritis with erosion based on endoscopy and pathology. Patients and treating physicians completed a questionnaire regarding history, endoscopic findings, and treatment plans as well as a follow-up questionnaire to investigate changes in symptoms after 4 wk of treatment. RESULTS: Three thousand five hundred sixty-three patients from 42 centers across 24 cities in China were included. Epigastric pain (68.0%), abdominal distension (62.6%), and postprandial fullness (47.5%) were the most common presenting symptoms. Gastritis was classified as chronic non-atrophic in 69.9% of patients. Among those with erosive lesions, 72.1% of patients had lesions in the antrum, 51.0% had multiple lesions, and 67.3% had superficial flat lesions. In patients with epigastric pain, the combination of a mucosal protective agent (MPA) and proton pump inhibitor was more effective. For those with postprandial fullness, acid regurgitation, early satiety, or nausea, a MPA appeared more promising. CONCLUSION: CEG is a multifactorial disease which is common in Asian patients and has non-specific symptoms. Gastroscopy may play a major role in its detection and diagnosis. Treatment should be individualized based on symptom profile.


Asunto(s)
Gastritis Atrófica , Gastritis , Infecciones por Helicobacter , Helicobacter pylori , Úlcera Gástrica , Humanos , Gastritis/diagnóstico , Gastritis/tratamiento farmacológico , Gastritis/epidemiología , Gastritis Atrófica/diagnóstico , Gastritis Atrófica/epidemiología , Gastritis Atrófica/patología , Úlcera Gástrica/patología , Gastroscopía , Dolor , Estilo de Vida , Mucosa Gástrica/patología , Infecciones por Helicobacter/patología
5.
J Am Chem Soc ; 146(11): 7616-7627, 2024 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-38446772

RESUMEN

Natural products and their analogues are significant sources of therapeutic lead compounds. However, synthetic strategies for generating large collections of these molecules remain a significant challenge. The most difficult step in their synthesis is the design of a common intermediate that can be easily transformed into natural products belonging to different families. This study demonstrates the evolution of synthetic tactics designed to assemble the functionalized piperidines present in indole alkaloids from a common intermediate. More importantly, we also report a previously unknown Ir- and Er-catalyzed dehydrogenative spirocyclization reaction that enables direct access to spirocyclic oxindole alkaloids. As a practical application, the asymmetric total syntheses of 29 natural alkaloids belonging to different families were accomplished by following a uniform synthetic route. The proposed methodology extends the capability of the iridium-catalyzed dehydrogenative coupling reaction to the realm of indole-alkaloid synthesis and provides new opportunities for the efficient preparation of natural product-like molecules.


Asunto(s)
Alcaloides , Productos Biológicos , Humanos , Estereoisomerismo , Alcaloides Indólicos , Oxindoles
6.
ACS Appl Mater Interfaces ; 16(7): 9060-9067, 2024 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-38336611

RESUMEN

Filter-free wavelength-selective photodetectors have garnered significant attention due to the growing demand for smart sensors, artificial intelligence, the Internet of Everything, and so forth. However, the challenges associated with large-scale preparation and compatibility with complementary metal-oxide-semiconductor (CMOS) technology limit their wide-ranging applications. In this work, we address the challenges by constructing vertically stacked graded-band-gap zinc-tin oxide (ZTO) thin-film transistors (TFTs) specifically designed for wavelength-selective photodetection. The ZTO thin films with various band gaps are fabricated via atomic layer deposition (ALD) by varying the ALD cycle ratios of zinc oxide (ZnO) and SnO2. The ZTO film with a small Sn ratio exhibits a decreased band gap, and the resultant TFT shows a degraded performance, which can be attributed to the Sn4+ dopant introducing a series of deep-state energy levels in the ZnO band gap. As the ratio of Sn increases further, the band gap of the ZTO also increases, and the mobility of the ZTO TFT increases up to 30 cm2/V s, with a positive shift of the threshold voltage. The photodetectors employing ZTO thin films with distinct band gaps show different spectral responsivities. Then, vertically stacked ZTO (S-ZTO) thin films, with gradient band gaps increasing from the bottom to the top, have been successfully deposited using consecutive ALD technology. The S-ZTO TFT shows decent performance with a mobility of 18.4 cm2/V s, a threshold voltage of 0.5 V, an on-off current ratio higher than 107, and excellent stability under ambient conditions. The resultant S-ZTO TFT also exhibits obviously distinct photoresponses to light at different wavelength ranges. Furthermore, a device array of S-ZTO TFTs demonstrates color imaging by precisely reconstructing patterned illuminations with different wavelengths. Therefore, this work provides CMOS-compatible and structure-compact wavelength-selective photodetectors for advanced and integrable optoelectronic applications.

7.
Dig Dis Sci ; 69(3): 949-960, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38218733

RESUMEN

BACKGROUND AND AIMS: Hybrid endoscopic submucosal dissection (H-ESD), a modified ESD with a snare, has become increasingly utilized to overcome the limitations of conventional ESD (C-ESD). This study aimed to compare the efficacy and safety of Planned H-ESD and C-ESD for colorectal lesions. METHODS: Propensity score matching was performed to control for confounding variables in this retrospective study. Outcomes included en bloc resection and complete resection (R0) rates, procedure time, adverse event rates, and local recurrence rate. RESULTS: 1286 lesions were enrolled in the study. After matching, 263 lesions were assigned to each group. The Planned H-ESD group has lower en bloc rate but similar R0 resection rate compared to the C-ESD group (90.9% vs 98.1%, P = 0.001; 77.2% vs 77.9%, P = 0.917). The median procedure time was shorter in the Planned H-ESD group (27.0 min vs 35.0 min, P = 0.001). There were no significant differences in adverse events rates or local recurrence rate. Subgroup analysis based on lesion size revealed that a significantly lower en bloc resection rate in the Planned H-ESD group compared to the C-ESD group for lesions ≥ 40 mm (71.0% vs 94.3%, P = 0.027), but there was no significant difference for lesions < 40 mm. CONCLUSION: The Planned H-ESD has a lower en bloc resection rate but a similar R0 resection rate, adverse event rates, local recurrence rate, and shorter procedure duration. Compared to C-ESD, Planned H-ESD presents advantages for managing colorectal neoplasms below 40 mm.


Asunto(s)
Neoplasias Colorrectales , Resección Endoscópica de la Mucosa , Humanos , Resultado del Tratamiento , Resección Endoscópica de la Mucosa/efectos adversos , Resección Endoscópica de la Mucosa/métodos , Puntaje de Propensión , Estudios Retrospectivos , Neoplasias Colorrectales/patología
8.
Curr Mol Med ; 2023 Nov 27.
Artículo en Inglés | MEDLINE | ID: mdl-38013443

RESUMEN

BACKGROUND: Colorectal cancer (CRC) is a malignant tumor. Slug has been found to display a key role in diversified cancers, but its relevant regulatory mechanisms in CRC development are not fully explored. OBJECTIVE: Hence, exploring the function and regulatory mechanisms of Slug is critical for the treatment of CRC. METHODS: Protein expressions of Slug, N-cadherin, E-cadherin, Snail, HIF-1α, SUMO1, Drp1, Opa1, Mfn1/2, PGC-1α, NRF1, and TFAM were measured through western blot. To evaluate the protein expression of Slug and SUMO-1, an immunofluorescence assay was used. Cell migration ability was tested through transwell assay. The SUMOylation of Slug was examined through CO-IP assay. RESULTS: Slug displayed higher expression and facilitated tumor metastasis in CRC. In addition, hypoxia treatment was discovered to upregulate HIF-1α, Slug, and SUMO-1 levels, as well as induce Slug SUMOylation. Slug SUMOylation markedly affected mitochondrial biosynthesis, fusion, and mitogen-related protein expression levels to trigger mitochondrial stress. Additionally, the induced mitochondrial stress by hypoxia could be rescued by Slug inhibition and TAK-981 treatment. CONCLUSION: Our study expounded that hypoxia affects mitochondrial stress and facilitates tumor metastasis of CRC through Slug SUMOylation.

9.
Front Plant Sci ; 14: 1179510, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37396648

RESUMEN

Sambucus L. is found in the family Viburnaceae (syn. Adoxaceae) and encompasses approximately 29 accepted species. The complex morphology of these species has caused continued confusion concerning their nomenclature, classification, and identification. Despite previous attempts to resolve taxonomic complexities in the Sambucus genus, there are still unclear phylogenetic relationships among several species. In this study, the newly obtained plastome of Sambucus williamsii Hance. as well as the populations of Sambucus canadensis L., Sambucus javanica Blume, and Sambucus adnata Wall. ex DC were sequenced, and their sizes, structural similarity, gene order, gene number, and guanine-cytosine (GC) contents were analyzed. The phylogenetic analyses were conducted using the whole chloroplast genomes and protein-coding genes (PCGs). The findings revealed that the chloroplast genomes of Sambucus species exhibited typical quadripartite double-stranded DNA molecules. Their lengths ranged from 158,012 base pairs (bp) (S. javanica) to 158,716 bp (S. canadensis L). Each genome comprised a pair of inverted repeats (IRs), which separated the large single-copy (LSC) and small single-copy (SSC) regions. In addition, the plastomes contained 132 genes, encompassing 87 protein-coding, 37 tRNA, and four rRNA genes. In the simple sequence repeat (SSR) analysis, A/T mononucleotides had the highest proportion, with the most repetitive sequences observed in S. williamsii. The comparative genome analyses showed high similarities in structure, order, and gene contents. The hypervariable regions in the studied chloroplast genomes were trnT-GGU, trnF-GAA, psaJ, trnL-UAG, ndhF, and ndhE, which may be used as candidate barcodes for species discrimination in Sambucus genus. Phylogenetic analyses supported the monophyly of Sambucus and revealed the separation of S. javanica and S. adnata populations. Sambucus chinensis Lindl. was nested within S. javanica in the same clade, collaborating their conspecific treatment. These outcomes indicate that the chloroplast genome of Sambucus plants is a valuable genetic resource for resolving taxonomic discrepancies at the lower taxonomic levels and can be applied in molecular evolutionary studies.

10.
ACS Macro Lett ; 12(7): 1005-1011, 2023 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-37409974

RESUMEN

The phase structure with a small domain size in polymers is expected to provide a template for lithography to fabricate electronic devices, while the uniformity and thermal stability of the phase structure are vital in lithography. In this work, we report an accurately microphase-separated system of comb-like poly(ionic liquid) (PIL)-based homopolymers containing imidazolium cation junctions between the main chain parts and the long alkyl side chains, poly(1-((2-acryloyloxy)ethyl)-3-alkylimidazolium bromide) (P(AOEAmI-Br)). The ordered hexagonally packed cylinder (HEX) and lamellar (LAM) structures with small domain sizes (sub-3 nm) were successfully achieved. Since the microphase separation was induced by the incompatibility between the main chain parts and the hydrophobic alkyl chains, the microdomain spacing of the ordered structure was independent of the molecular weight and molecular weight distribution of P(AOEAmI-Br) homopolymers and could be precisely regulated by changing the length of the alkyl side chains. Importantly, the microphase separation was promoted by the charged junction groups; thus, the phase structure and domain size of P(AOEAmI-Br) exhibited excellent thermal stability.

11.
Foods ; 12(14)2023 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-37509774

RESUMEN

Cultured meat is one of the meat substitutes produced through tissue engineering and other technologies. Large-scale cell culture is the key for cultured meat products to enter the market. Therefore, this study is aimed to explore the effect of long-term passage in vitro on smooth muscle cells (SMCs) and the effect of transforming growth factor-ß1 (TGF-ß1) on SMCs in the late passage. Multiple passages lead to the decline of the proliferation rate of SMCs in the proliferation stage and the differentiation ability in the differentiation stage. Transcriptome results showed that the ECM pathway and aging-related signaling pathways were significantly up-regulated in the late passage period. TGF-ß1 did not promote SMCs of late passage proliferation at the proliferation stage but promoted the gene and protein expression of collagen as the main protein of the extracellular matrix proteins at the differentiation stage. In addition, proteomic analysis revealed that TGF-ß1 promoted the expression of cell adhesion molecules which activate the Hippo signaling pathway and the HIF-1 signaling pathway and further promoted the production of collagen-containing extracellular matrix proteins. This could provide ideas for large-scale production of cultured meat products using SMCs.

12.
Sci Total Environ ; 892: 164567, 2023 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-37268120

RESUMEN

Atmospheric particulate matter (PM) enriched with lead (Pb) has severe irreversible effects on human health. Therefore, identifying the contribution of Pb emission sources is essential for protecting the health of residents. Using the Pb isotopic tracer method, this study explored the seasonal characteristics and primary anthropogenic Pb sources for atmospheric PM in Tianjin in 2019. We calculated the contribution of Pb sources using the end-member and MixSIAR models. The results showed that Pb loaded in PM10 was more abundant in January than in July, and was strongly influenced by meteorological conditions and anthropogenic emissions. The primary Pb sources of the aerosol samples originated from coal combustion and vehicle and steel plant emissions, mainly originating from local Pb emission sources in Tianjin. The PM10-bond Pb in January was influenced by regional transportation and local sources. The MixSIAS model calculated the contribution of coal combustion as approximately 50 %. Compared with that in January, the contribution of coal combustion decreased by 9.6 % in July. Our results indicate that some of the benefits of phased-out leaded gasoline have been short-lived, whereas other industrial activities releasing Pb have increased. Furthermore, the results emphasise the practicability of the Pb isotope tracer source approach for identifying and distinguishing between different anthropogenic Pb inputs. Based on this study, scientific and effective air pollution prevention and control programs can be formulated to provide decision support for the guidance and control of air pollutant emissions.


Asunto(s)
Contaminantes Atmosféricos , Plomo , Humanos , Plomo/análisis , Teorema de Bayes , Material Particulado/análisis , Contaminantes Atmosféricos/análisis , Isótopos/análisis , Carbón Mineral/análisis , Monitoreo del Ambiente/métodos , China
13.
Nanomaterials (Basel) ; 13(11)2023 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-37299668

RESUMEN

Concurrently achieving high energy storage density (ESD) and efficiency has always been a big challenge for electrostatic energy storage capacitors. In this study, we successfully fabricate high-performance energy storage capacitors by using antiferroelectric (AFE) Al-doped Hf0.25Zr0.75O2 (HfZrO:Al) dielectrics together with an ultrathin (1 nm) Hf0.5Zr0.5O2 underlying layer. By optimizing the Al concentration in the AFE layer with the help of accurate controllability of the atomic layer deposition technique, an ultrahigh ESD of 81.4 J cm-3 and a perfect energy storage efficiency (ESE) of 82.9% are simultaneously achieved for the first time in the case of the Al/(Hf + Zr) ratio of 1/16. Meanwhile, both the ESD and ESE exhibit excellent electric field cycling endurance within 109 cycles under 5~5.5 MV cm-1, and robust thermal stability up to 200 °C. Thus, the fabricated capacitor is very promising for on-chip energy storage applications due to favorable integratability with the standard complementary metal-oxide-semiconductor (CMOS) process.

14.
Microb Biotechnol ; 16(10): 1924-1939, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37377410

RESUMEN

It has been reported that Akkermansia muciniphila improves host metabolism and reduces inflammation; however, its potential effects on bile acid metabolism and metabolic patterns in metabolic-associated fatty liver disease (MAFLD) are unknown. In this study, we have analysed C57BL/6 mice under three feeding conditions: (i) a low-fat diet group (LP), (ii) a high-fat diet group (HP) and (iii) a high-fat diet group supplemented with A. muciniphila (HA). The results found that A. muciniphila administration relieved weight gain, hepatic steatosis and liver injury induced by the high-fat diet. A. muciniphila altered the gut microbiota with a decrease in Alistipes, Lactobacilli, Tyzzerella, Butyricimonas and Blautia, and an enrichment of Ruminiclostridium, Osclibacter, Allobaculum, Anaeroplasma and Rikenella. The gut microbiota changes correlated significantly with bile acids. Meanwhile, A. muciniphila also improved glucose tolerance, gut barriers and adipokines dysbiosis. Akkermansia muciniphila regulated the intestinal FXR-FGF15 axis and reshaped the construction of bile acids, with reduced secondary bile acids in the caecum and liver, including DCA and LCA. These findings provide new insights into the relationships between probiotics, microflora and metabolic disorders, highlighting the potential role of A. muciniphila in the management of MAFLD.


Asunto(s)
Microbioma Gastrointestinal , Hepatopatías , Enfermedades Metabólicas , Animales , Ratones , Dieta Alta en Grasa/efectos adversos , Ácidos y Sales Biliares/farmacología , Ratones Endogámicos C57BL , Verrucomicrobia
15.
Curr Med Chem ; 2023 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-37151058

RESUMEN

Gastrointestinal stromal tumour (GIST) is a common gastrointestinal sarcoma located in the stromal cells of the digestive tract, and molecular studies have revealed the pathogenesis of mutations in KIT and PDGFRA genes. Since imatinib opened the era of targeted therapy for GIST, tyrosine kinase inhibitors (TKIs) that can treat GIST have been developed successively. However, the lack of new drugs with satisfactory therapeutic standards has made addressing resistance a significant challenge for TKIs in the face of the resistance to first-line and second-line drugs. Therefore, we need to find as many drugs and new treatments that block mutated genes as possible. METHODS: We conducted a comprehensive collection of literature using databases, integrated and analysed the selected literature based on keywords and the comprehensive nature of the articles, and finally wrote articles based on the content of the studies. RESULTS: In this article, we first briefly explained the relationship between GIST and KIT/ PDGFRα and then introduced the related drug treatment. The research progress of TKIs was analyzed according to the resistance of the drugs. CONCLUSION: This article describes the research progress of some TKIs and provides a brief introduction to the currently approved TKIs and some drugs under investigation that may have better therapeutic effects, hoping to provide clues to the research of new drugs.

16.
Front Pharmacol ; 14: 1148814, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37025486

RESUMEN

Background: Non-alcoholic fatty liver disease (NAFLD) is a chronic advanced liver disease that is highly related to metabolic disorders and induced by a high-fat diet (HFD). Recently, epigallocatechin gallate (EGCG) has been regarded as a protective bioactive polyphenol in green tea that has the ability to protect against non-alcoholic fatty liver disease, but the molecular mechanism remains poorly deciphered. Ferroptosis plays a vital role in the progression of non-alcoholic fatty liver disease, but experimental evidence of ferroptosis inhibition by epigallocatechin gallate is limited. Hence, our study aimed to investigate the effect and mechanisms of epigallocatechin gallate on hepatic ferroptosis to mitigate hepatic injury in high-fat diet-fed mice. Methods: Fifty male C57BL/6 mice were fed either a standard chow diet (SCD), a high-fat diet, or a high-fat diet and administered epigallocatechin gallate or ferrostatin-1 (a ferroptosis-specific inhibitor) for 12 weeks. Liver injury, lipid accumulation, hepatic steatosis, oxidative stress, iron overload, and ferroptosis marker proteins were examined. In vitro, steatotic L-02 cells were used to explore the underlying mechanism. Results: In our research, we found that epigallocatechin gallate notably alleviated liver injury and lipid accumulation, oxidative stress, hepatic steatosis, decreased iron overload and inhibited ferroptosis in a high-fat diet-induced murine model of non-alcoholic fatty liver disease. In vitro experiments, using ferrostatin-1 and a mitochondrial reactive oxygen species (MtROS) scavenger (Mito-TEMPO), we found that epigallocatechin gallate remarkably alleviated oxidative stress and inhibited ferroptosis by reducing the level of mitochondrial reactive oxygen species in steatotic L-02 cells. Conclusion: Taken together, our results revealed that epigallocatechin gallate may exert protective effects on hepatic lipotoxicity by inhibiting mitochondrial reactive oxygen species-mediated hepatic ferroptosis. Findings from our study provide new insight into prevention and treatment strategies for non-alcoholic fatty liver disease pathological processes.

17.
J Clin Lab Anal ; 37(6): e24875, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37003602

RESUMEN

BACKGROUND: Whether the levels of circulating inflammatory adipokines affect the progression of type 2 diabetes (T2D) remains unclear. This study aimed to assess the association between circulating inflammatory adipokine levels and risk of T2D. METHODS: This case-control study involved 130 individuals consisting of 66 healthy controls (Control group) and 64 patients with T2D (T2D group) in Lishui Municipal Central Hospital from January 2017 to June 2017. Multivariate logistic regression analysis was applied to assess the associations between circulating inflammatory adipokine levels and the risk of T2D. RESULTS: There were significant differences in the levels of adiponectin (p = 0.013) and visfatin (p < 0.001) between the T2D and Control groups. In contrast, no significant differences in leptin (p = 0.113), TNF-α (p = 0.632), and IL-6 (p = 0.156) levels were found between the groups. Multivariate logistic regression indicated that elevated visfatin level was associated with an increased risk of T2D (OR: 3.543; 95% CI: 1.771-7.088; p < 0.001), while adiponectin (OR: 1.946; 95% CI: 0.925-4.094; p = 0.079), leptin (OR: 3.723; 95% CI: 0.788-17.583; p = 0.097), TNF-α (OR: 1.081; 95% CI: 0.911-1.281; p = 0.373), and IL-6 (OR: 0.878; 95% CI: 0.657-1.173; p = 0.379) were not associated with the risk of T2D. CONCLUSIONS: This study found elevated visfatin levels are associated with an increased risk of T2D, while adiponectin, leptin, TNF-α, and IL-6 are not. These findings should be further verified by a large-scale prospective study.


Asunto(s)
Adipoquinas , Diabetes Mellitus Tipo 2 , Humanos , Masculino , Leptina , Adiponectina , Nicotinamida Fosforribosiltransferasa , Diabetes Mellitus Tipo 2/epidemiología , Factor de Necrosis Tumoral alfa , Interleucina-6 , Estudios Prospectivos , Estudios de Casos y Controles , Pueblos del Este de Asia
18.
Food Res Int ; 165: 112486, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36869499

RESUMEN

Cultured fat is inducing adipose progenitor cells (APCs) to differentiate into mature adipocytes for consumption. The traditional adipogenic differentiation cocktail, including insulin, dexamethasone, indomethacin, isobutylmethylxanthine and rosiglitazone, has potential food safety problems in cultured fat. Therefore, the detection of these residues is necessary to ensure food safety. In this research, a method of high performance liquid chromatography (HPLC) was established to quantitatively analyze the potential residual content of dexamethasone, indomethacin, isobutylmethylxanthine and rosiglitazone in cultured fat and medium. Quantitative analysis showed that the content of four residues in cultured fat decreased to zero on Day 10. Subsequently, enzyme-linked immunosorbent assay (ELISA) was performed to detect the insulin content in the cultured fat and found that the insulin content in the cultured fat on Day 10 was 2.78 ± 0.21 µg/kg. After soaking with phosphate buffered saline (PBS), the insulin content decreased to 1.88 ± 0.54 µg/kg. In conclusion, this research provided an effective approach to clarify the content of potential residual components in cultured fat and it will provide reference for the safety of cultured fat in the future.


Asunto(s)
Inocuidad de los Alimentos , Insulina , Cromatografía Líquida de Alta Presión , Rosiglitazona , Diferenciación Celular , Ensayo de Inmunoadsorción Enzimática , Indometacina , Dexametasona
19.
Food Res Int ; 166: 112606, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36914351

RESUMEN

Cultured meat is an efficient, safe and sustainable meat production technology. Adipose-derived stem cell (ADSC) is a promising cell type for cultured meat. In vitro, obtaining numerous of ADSCs is a pivotal step for cultured meat. In this research, we demonstrated that the proliferation and adipogenic differentiation of ADSCs significantly decreased during serial passage. Then, senescence ß-galactosidase (SA-ß-gal) staining showed that the positive rate of P9 ADSCs was 7.74-fold than P3 ADSCs. Subsequently, RNA sequencing (RNA-seq) was performed for P3 and P9 ADSCs and found that PI3K-AKT pathway was up-regulated, but cell cycle and DNA repair pathway were down-regulated in P9 ADSCs. Then, N-Acetylcysteine (NAC) was added during long-term expansion and showed that NAC enhanced the ADSCs proliferation and maintained adipogenic differentiation. Finally, RNA-seq was performed for P9 ADSCs cultured with or without NAC and showed that NAC restored the cell cycle and DNA repair pathway in P9 ADSCs. These results highlighted that NAC was an excellent supplement for large-scale expansion of porcine ADSCs for cultured meat.


Asunto(s)
Acetilcisteína , Tejido Adiposo , Animales , Porcinos , Tejido Adiposo/metabolismo , Acetilcisteína/farmacología , Acetilcisteína/metabolismo , Células Madre/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proliferación Celular
20.
Nanoscale ; 15(9): 4553-4560, 2023 Mar 02.
Artículo en Inglés | MEDLINE | ID: mdl-36757829

RESUMEN

For the bulk self-assembly of traditional diblock copolymers (di-BCPs), lamellar structures only occur when two constituents have similar volume fractions (f) and two alternating layers tend to have similar thicknesses. Highly asymmetric lamellar (A-LAM) structures, in which the thickness of one layer is several times higher than the other, are hardly formed in di-BCPs, while they have potential applications in nanolithography. In this work, A-LAM structures with different dimensions were constructed using a type of simple linear di-BCP, polystyrene-b-poly(4-vinylpyridine)propane-1-sulfonate (PS-b-PVPS) with the polyzwitterionic block PVPS in minority. The origin of the A-LAM structure was ascribed to the electrostatic crosslinking and confirmed by doping PS-b-PVPS block copolymers (BCPs) with N-butyl pyridinium methane sulfonate (BPMS). The morphology of compositionally asymmetric PS-b-PVPS BCPs changed from A-LAM to cylindrical structures upon salt-doping, i.e. the phase behavior of common BCPs was recovered. In addition, the morphologies of PS-b-PVPS BCPs with similar molecular weights but varied compositions were also studied, and only two kinds of structures (lamellar or ill-defined spherical structure) were observed when the volume fraction of PVPS (fPVPS) was less than 0.5, and the composition range for the formation of the lamellar structure was found to be fPVPS ≥ 0.188.

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