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1.
Int J Biol Macromol ; 278(Pt 4): 134986, 2024 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-39181362

RESUMEN

Endocrine tumors like thyroid carcinoma are becoming more frequent. No clinically informative predictors were found. Thus, effective gene networks and representative biomarkers can illuminate thyroid cancer prevention molecular mechanisms. TBC1D4 is an activating protein molecule that plays an important role in regulating cell metabolism and signal transduction. The aim of this study was to investigate the expression characteristics of TBC1D4 activating protein molecules and identify key module genes that prevent thyroid cancer progression. GSE65144 data were downloaded from GEO. "limma" in R found DEGs with a false discovery rate < 0.05 and a log2 fold change <1. WGCNA builds gene co-expression networks, screens key modules, and filters hub genes. Overlapping genes become hub genes. Hub genes underwent GO and KEGG pathway enrichment analysis. We used Lasso to extract hub gene expression results' distinctive genes. Key genes. GEPIA database determined expression and survival impact. A total of 3220 DEGs. Thyroid cancer was mostly associated with darkred, darkturquoise, and green modules. Venn screened 639 hub genes. Cytokine-cytokine receptor interaction was the primary KEGG enrichment. Hub genes were 14. Finally, ARHGAP6, TBC1D4, and TC2N were important genes. Through gene screening and functional enrichment analysis, we identified a group of genes related to TBC1D4 activating protein and constructed the corresponding protein interaction network.

2.
Int J Biol Macromol ; 278(Pt 1): 134629, 2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39128756

RESUMEN

Hepatocellular carcinoma, also referred to as HCC, is the most frequent form of primary liver cancer. It is anticipated that the discovery of the molecular pathways related with HCC would open up new possibilities for the treatment of HCC.WGCNA (Weighted gene co-expression network analysis) and molecular docking analysis were used to study the structural characteristics of POU2AF1 recombinant protein and its interaction with related proteins. Normal samples were placed in one group, and tumor samples were placed in another group inside the GEO database. We continued our investigation of the DEGs by performing an enrichment analysis using GO and KEGG. The GSCA platform is utilized in the process of doing an analysis of the connection between gene expression and medication sensitivity. In the end, the core target and the active molecule were both given the green light for a molecular docking investigation. POU2AF1 is being considered as a possible therapeutic target for HCC, and the results of our work have presented novel concepts for the treatment of HCC.

3.
J Environ Manage ; 367: 121972, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39079493

RESUMEN

Cooperative green technology innovation is potentially the answer to the lack of motivation for independent green innovation, which can effectively alleviate many difficulties faced by enterprises engaging in independent green innovation. Internet development provides new opportunities to stimulate innovative cooperation of enterprises. However, little literature has studied the impact of Internet development on enterprises' cooperative green technology innovation. Based on the data of Chinese A-share 3284 listed companies from 2010 to 2019, this paper uses a panel two-way fixed effects model to assess the effect of Internet development on enterprises' cooperative green innovation. The findings are: (1) Internet development significantly drives firms' collaborative green innovation behavior. The result remains robust even after performing a series of robust tests. (2) The Internet empowers green innovation cooperation among firms by improving information availability, including market information availability and technical information availability. (3) The heterogeneous results show enterprises use the Internet to accomplish high-quality collaborative green innovation. Internet development is more helpful in encouraging the cooperative green innovation of enterprises located in central cities and state-owned enterprises. This study provides novel and targeted policy implications to empower enterprises' green innovation cooperation and drive sustainable economic development through Internet development.


Asunto(s)
Internet , China , Invenciones , Desarrollo Económico , Tecnología , Pueblos del Este de Asia
4.
Cell Commun Signal ; 22(1): 300, 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38816763

RESUMEN

Optimizing the efficiency of definitive endoderm (DE) differentiation is necessary for the generation of diverse organ-like structures. In this study, we used the small molecule inhibitor saracatinib (SAR) to enhance DE differentiation of human embryonic stem cells and induced pluripotent stem cells. SAR significantly improved DE differentiation efficiency at low concentrations. The interaction between SAR and Focal Adhesion Kinase (FAK) was explored through RNA-seq and molecular docking simulations, which further supported the inhibition of DE differentiation by p-FAK overexpression in SAR-treated cells. In addition, we found that SAR inhibited the nuclear translocation of Yes-associated protein (YAP), a downstream effector of FAK, which promoted DE differentiation. Moreover, the addition of SAR enabled a significant reduction in activin A (AA) from 50 to 10 ng/mL without compromising DE differentiation efficiency. For induction of the pancreatic lineage, 10 ng/ml AA combined with SAR at the DE differentiation stage yielded a comparative number of PDX1+/NKX6.1+ pancreatic progenitor cells to those obtained by 50 ng/ml AA treatment. Our study highlights SAR as a potential modulator that facilitates the cost-effective generation of DE cells and provides insight into the orchestration of cell fate determination.


Asunto(s)
Benzodioxoles , Diferenciación Celular , Endodermo , Quinazolinas , Transducción de Señal , Humanos , Diferenciación Celular/efectos de los fármacos , Endodermo/efectos de los fármacos , Endodermo/citología , Endodermo/metabolismo , Benzodioxoles/farmacología , Transducción de Señal/efectos de los fármacos , Quinazolinas/farmacología , Factores de Transcripción/metabolismo , Células Madre Pluripotentes Inducidas/efectos de los fármacos , Células Madre Pluripotentes Inducidas/metabolismo , Células Madre Pluripotentes Inducidas/citología , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Proteínas Señalizadoras YAP/metabolismo , Quinasa 1 de Adhesión Focal/metabolismo , Quinasa 1 de Adhesión Focal/genética , Células Madre Embrionarias Humanas/efectos de los fármacos , Células Madre Embrionarias Humanas/metabolismo , Células Madre Embrionarias Humanas/citología , Activinas/metabolismo , Simulación del Acoplamiento Molecular
5.
Plant Cell Rep ; 43(6): 136, 2024 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-38709311

RESUMEN

KEY MESSAGE: In our study, we discovered a fragment duplication autoregulation mechanism in 'ZS-HY', which may be the reason for the phenotype of red foliage and red flesh in grapes. In grapes, MYBA1 and MYBA2 are the main genetic factors responsible for skin coloration which are located at the color loci on chromosome 2, but the exact genes responsible for color have not been identified in the flesh. We used a new teinturier grape germplasm 'ZhongShan-HongYu' (ZS-HY) which accumulate anthocyanin both in skin and flesh as experimental materials. All tissues of 'ZS-HY' contained cyanidin 3-O-(6″-p-coumaroyl glucoside), and pelargonidins were detected in skin, flesh, and tendril. Through gene expression analysis at different stage of flesh, significant differences in the expression levels of VvMYBA1 were found. Gene amplification analysis showed that the VvMYBA1 promoter is composed of two alleles, VvMYBA1a and 'VvMYBA1c-like'. An insertion of a 408 bp repetitive fragment was detected in the allele 'VvMYBA1c-like'. In this process, we found the 408 bp repetitive fragment was co-segregated with red flesh and foliage phenotype. Our results revealed that the 408 bp fragment replication insertion in promoter of 'VvMYBA1c-like' was the target of its protein, and the number of repeat fragments was related to the increase of trans-activation of VvMYBA1 protein. The activation of promoter by VvMYBA1 was enhanced by the addition of VvMYC1. In addition, VvMYBA1 interacted with VvMYC1 to promote the expression of VvGT1 and VvGST4 genes in 'ZS-HY'. The discovery of this mutation event provides new insights into the regulation of VvMYBA1 on anthocyanin accumulation in red-fleshed grape, which is of great significance for molecular breeding of red-fleshed table grapes.


Asunto(s)
Antocianinas , Regulación de la Expresión Génica de las Plantas , Fenotipo , Proteínas de Plantas , Regiones Promotoras Genéticas , Factores de Transcripción , Vitis , Vitis/genética , Vitis/metabolismo , Regiones Promotoras Genéticas/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Antocianinas/metabolismo , Antocianinas/genética , Pigmentación/genética , Frutas/genética , Frutas/metabolismo , Alelos
6.
Cancer Lett ; 588: 216738, 2024 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-38401887

RESUMEN

The gastrointestinal tract can be affected by a number of diseases that pancreatic cancer (PC) is a malignant manifestation of them. The prognosis of PC patients is unfavorable and because of their diagnosis at advanced stage, the treatment of this tumor is problematic. Owing to low survival rate, there is much interest towards understanding the molecular profile of PC in an attempt in developing more effective therapeutics. The conventional therapeutics for PC include surgery, chemotherapy and radiotherapy as well as emerging immunotherapy. However, PC is still incurable and more effort should be performed. The molecular landscape of PC is an underlying factor involved in increase in progression of tumor cells. In the presence review, the newest advances in understanding the molecular and biological events in PC are discussed. The dysregulation of molecular pathways including AMPK, MAPK, STAT3, Wnt/ß-catenin and non-coding RNA transcripts has been suggested as a factor in development of tumorigenesis in PC. Moreover, cell death mechanisms such as apoptosis, autophagy, ferroptosis and necroptosis demonstrate abnormal levels. The EMT and glycolysis in PC cells enhance to ensure their metastasis and proliferation. Furthermore, such abnormal changes have been used to develop corresponding pharmacological and nanotechnological therapeutics for PC.


Asunto(s)
Neoplasias Pancreáticas , Humanos , Línea Celular Tumoral , Proliferación Celular/genética , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/genética , Apoptosis , Pronóstico
7.
J Agric Food Chem ; 72(8): 4433-4447, 2024 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-38354220

RESUMEN

Astringency influences the sensory characteristics and flavor quality of table grapes. We tested the astringency sensory attributes of berries and investigated the concentration of flavan-3-ols/proanthocyanidins (PAs) in skins after the application of the plant growth regulators CPPU and GA3 to the flowers and young berries of the "Summer Black" grape. Our results showed that CPPU and GA3 applications increase sensory astringency perception scores and flavan-3-ol/proanthocyanidin concentrations. Using integrated transcriptomic and proteomic analysis, differentially expressed transcripts and proteins associated with growth regulator treatment were identified, including those for flavonoid biosynthesis that contribute to the changes in sensory astringency levels. Transient overexpression of candidate astringency-related regulatory genes in grape leaves revealed that VvWRKY71, in combination with VvMYBPA1 and VvMYC1, could promote the biosynthesis of proanthocyanidins, while overexpression of VvNAC83 reduced the accumulation of proanthocyanidins. However, in transient promoter studies in Nicotiana benthamiana, VvWRKY71 repressed the promoter of VvMYBPA2, while VvNAC83 had no significant effect on the promoter activity of four PA-related genes, and VvMYBPA1 was shown to activate its own promoter. This study provides new insights into the molecular mechanisms of sensory astringency formation induced by plant growth regulators in grape berries.


Asunto(s)
Polietilenglicoles , Poliuretanos , Proantocianidinas , Vitis , Proantocianidinas/metabolismo , Vitis/metabolismo , Frutas/metabolismo , Reguladores del Crecimiento de las Plantas/metabolismo , Astringentes/metabolismo , Proteómica , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Perfilación de la Expresión Génica , Genes Reguladores , Regulación de la Expresión Génica de las Plantas
8.
Int J Dent ; 2024: 5768318, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38264680

RESUMEN

Objective: To evaluate the influence of screw-tightening methods on the immediate and long-term stability of dental implant screw joints. Methodology. A total of 150 implants of three different implant systems with different diameters were used in this study. Each group was divided into three subgroups (n = 5), according to the tightening methods (A-tightening with recommended torque and retorque after 10 min; B-tightening with recommended torque, then loosening and immediate retorque; C-tightening with recommended torque only once). The operating time of tightening the assemblies was recorded. Ten minutes later, the immediate removal torque (IRT) (Ncm) was measured. After retightening the assemblies, a dynamic load between 20 and 200 N was applied for 105 cycles, and the postloading removal torque (PRT) (Ncm) was measured. Scanning electron microscopy (SEM) was used to observe the surface topography of the screws. Results: For different types of implants, the IRTs were 11.92 ± 1.04-34.12 ± 0.36 Ncm for method A, 11.64 ± 0.57-33.96 ± 0.29 Ncm for method B, and 10.30 ± 0.41-31.62 ± 0.52 Ncm for method C, and the IRTs of methods A and B were 6.28%-21.58% higher than that of method C (P ≤ 0.046). The PRTs were 4.08 ± 0.77-29.86 ± 0.65 Ncm for method A, 4.04 ± 0.40-29.60 ± 0.36 Ncm for method B, and 2.98 ± 0.26-26.38 ± 0.59 Ncm for method C, and the PRTs of methods A and B were 11.77%-44.87% higher than that of method C (P ≤ 0.016). The removal torque loss rates of methods A (12.49% ± 0.99%-65.88% ± 4.83%) and B (12.84% ± 0.96%-65.35% ± 1.95%) were 3.04%-7.74% lower than that of method C (16.58% ± 0.56%-71.10% ± 1.58%) (P ≤ 0.017). The operating time of method A was much longer than those of methods B and C (P < 0.001). The structural integrity disruption of the screw thread was observed according to the SEM results in all postloading groups. Conclusions: Method B (torquing and then loosening and immediate retorquing) increases the screw joint immediate stability by 6.28%-21.58% and the long-term stability by 11.77%-44.87% compared with method C (torquing only once), has comparable screw joint stability compared with method A (retorquing after 10 min), saves time and is recommended in clinical settings.

9.
J Environ Manage ; 348: 119281, 2023 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-37837763

RESUMEN

Combating climate change and reducing carbon dioxide emissions are serious challenges shared by countries around the world. In the current era, digitalization has a significant impact on CO2 emissions. However, prior studies have not assessed the synergy between digitalization and industrialization on carbon emission performance. The principal component analysis and non-radial directional distance function (NDDF) are used to measure the digitalization and total factor carbon emission performance of Chinese 245 prefecture-level cities from 2003 to 2019. This study establishes a fixed effects model to study the panel data. The findings are as follows: (1) Digitalization can significantly promote Chinese cities' CO2 emission reduction. This result still holds after several robustness checks. (2) The heterogeneity results indicate that digitalization mainly improves central cities' carbon emission performance. Meanwhile, the impact of digitalization is more obvious after 2011. (3) Digitalization improves urban carbon emission performance through energy efficiency, industrial transformation, and technological innovation. (4) It is worth noting that digitalization synergizes with industrialization to improve carbon emission performance in Chinese cities. This study provides empirical evidence and some constructive policy recommendations for the government to push the collaborative development of the digitalization and low-carbon economy.


Asunto(s)
Dióxido de Carbono , Desarrollo Industrial , Industrias , Ciudades , Cambio Climático , China , Desarrollo Económico
10.
Cytokine Growth Factor Rev ; 73: 69-77, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37684117

RESUMEN

Pancreatic cancer is characterized by its high malignancy, insidious onset and poor prognosis. Most patients with pancreatic cancer are usually diagnosed at advanced stage or with the distant metastasis due to the lack of an effective early screening method. Liquid biopsy technology is promising in studying the occurrence, progression, and early metastasis of pancreatic cancer. In particular, exosomes are pivotal biomarkers in lipid metabolism and liquid biopsy of blood exosomes is valuable for the evaluation of pancreatic cancer. Lipid metabolism is crucial for the formation and activity of exosomes in the extracellular environment. Exosomes and lipids have a complex relationship of mutual influence. Furthermore, spatial metabolomics can quantify the levels and spatial locations of individual metabolites in cancer tissue, cancer stroma, and para-cancerous tissue in pancreatic cancer. However, the relationship among exosomes, lipid metabolism, and pancreatic cancer is also worth considering. This study mainly updates the research progress of metabolomics in pancreatic cancer, their relationship with exosomes, an important part of liquid biopsy, and their lipometabolic roles in pancreatic cancer. We also discuss the mechanisms by which possible metabolites, especially lipid metabolites through exosome transport and other processes, contribute to the recurrence and metastasis of pancreatic cancer.

11.
Mol Cancer ; 22(1): 98, 2023 06 21.
Artículo en Inglés | MEDLINE | ID: mdl-37344887

RESUMEN

Cancer is a grievous disease whose treatment requires a more efficient, non-invasive therapy, associated with minimal side effects. Gold nanoparticles possessing greatly impressive optical properties have been a forerunner in bioengineered cancer therapy. This theranostic system has gained immense popularity and finds its application in the field of molecular detection, biological imaging, cancer cell targeting, etc. The photothermal property of nanoparticles, especially of gold nanorods, causes absorption of the light incident by the light source, and transforms it into heat, resulting in tumor cell destruction. This review describes the different optical features of gold nanoparticles and summarizes the advance research done for the application of gold nanoparticles and precisely gold nanorods for combating various cancers including breast, lung, colon, oral, prostate, and pancreatic cancer.


Asunto(s)
Nanopartículas del Metal , Nanotubos , Neoplasias , Masculino , Humanos , Oro/uso terapéutico , Nanopartículas del Metal/uso terapéutico , Neoplasias/tratamiento farmacológico , Diagnóstico por Imagen , Línea Celular Tumoral
12.
Pharmacol Res ; 193: 106812, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37271425

RESUMEN

Polyphenols, also known as phenolic compounds, are chemical substances containing aromatic rings as well as at least two hydroxyl groups. Natural phenolic compounds exist widely in plants, which protect plants from ultraviolet radiation and other insults. Phenolic compounds have superior pharmacological and nutritional properties (antimicrobial, antibacterial, antiviral, anti-sclerosis, antioxidant, and anti-inflammatory activities), which have been paid more and more attention by the scientific community. Phenols can protect key cellular components from reactive free radical damage, which is mainly due to their property to activate antioxidant enzymes and alleviate oxidative stress and inflammation. It can also inhibit or isolate reactive oxygen species and transfer electrons to free radicals, thereby avoiding cell damage. It has a regulatory role in glucose metabolism, which has a promising prospect in the prevention and intervention of diabetes. It also prevents cardiovascular disease by regulating blood pressure and blood lipids. Polyphenols can inhibit cell proliferation by affecting Erk1/2, CDK, and PI3K/Akt signaling pathways. Polyphenols can function as enhancers of intrinsic defense systems, including superoxide dismutase (SOD) and glutathione peroxidase (GPX). Simultaneously, they can modulate multiple proteins and transcription factors, making them promising candidates in the investigation of anti-cancer medications. This review focuses on multiple aspects of phenolic substances, including their natural origins, production process, disinfection activity, oxidative and anti-inflammatory functions, and the effects of different phenolic substances on tumors.


Asunto(s)
Antioxidantes , Neoplasias , Humanos , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Antioxidantes/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Rayos Ultravioleta , Estrés Oxidativo , Fenoles/farmacología , Fenoles/uso terapéutico , Neoplasias/tratamiento farmacológico , Polifenoles/farmacología , Radicales Libres/metabolismo , Inflamación/tratamiento farmacológico , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Antiinflamatorios/química
13.
Transplantation ; 107(8): 1729-1739, 2023 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-36698245

RESUMEN

BACKGROUND: Renal ischemia/reperfusion (I/R) injury is one of the crucial factors affecting the outcome of renal transplantation. In recent years, myeloid-derived growth factor (MYDGF) has received a lot of attention for its extensive beneficial effects on cardiac repair and protection of cardiomyocytes from cell death. Therefore, we hypothesized that the recombinant human MYDGF (rhMYDGF) protein might play an essential role in safeguarding renal I/R injury. METHODS: In vivo experiments were conducted using a mouse unilateral I/R model. Mice were pretreated with rhMYDGF by intraperitoneal injection to study the potential mechanism of renal protection. In vitro, we established hypoxia/reoxygenation and H 2 O 2 treatment models to pretreat cells with rhMYDGF. The expression levels of oxidative stress, inflammation, and apoptosis-related factors in tissues and cells were detected. Finally, we explored the role of the protein kinase B (Akt) pathway in the renal protective mechanism of rhMYDGF. RESULTS: In this study, we found that intraperitoneal injection of 1.25 µg rhMYDGF could significantly improve renal function of I/R mice, and reduce oxidative stress, inflammation, and apoptosis. For the human proximal tubular epithelial cell line and human kidney cell line, pretreatment with 0.3 µg/mL rhMYDGF for 24 h significantly downregulated oxidative stress, inflammation, and apoptosis via the phosphorylation of Akt, which could be ameliorated by LY294002. CONCLUSIONS: rhMYDGF protects kidney from I/R injury by attenuating oxidative stress, inflammation, and apoptosis through the activation of the Akt pathway.


Asunto(s)
Proteínas Proto-Oncogénicas c-akt , Daño por Reperfusión , Humanos , Apoptosis , Inflamación/prevención & control , Inflamación/metabolismo , Riñón , Estrés Oxidativo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Daño por Reperfusión/prevención & control , Daño por Reperfusión/metabolismo , Transducción de Señal , Proteínas Recombinantes/metabolismo
14.
Clin Oral Investig ; 27(1): 221-233, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36161530

RESUMEN

OBJECTIVES: To investigate the fracture strength of angulated hybrid abutments supporting anterior single crowns on narrow-diameter implants (NDIs). MATERIAL AND METHODS: Zirconia abutment with angulations of labial inclination 0° (TZ0Z), 15° (TZ15Z), 30° (TZ30Z) and palatal inclination 15° (TZ - 15Z) was designed on 3.3-mm titanium-zirconium (Ti-Zr) NDIs. Titanium abutment connected with Ti-Zr implant (TZ0T) and 0° zirconia abutment connected with pure titanium (Ti) implant (T0Z) were control groups. Thirty-six un-restored abutments and 36 abutments restored with highly translucent zirconia (HTZ) crowns were tested. Failure loads were compared among 6 groups, and bending moments were calculated for comparison between un-restored and restored abutments. RESULTS: Failure loads of un-restored abutments were affected by the abutment angle. Sixty-seven percent samples in TZ30Z and 83% samples in TZ - 15Z group fractured at the thinnest part of the zirconia abutment and exhibited lower failure load (p < .05). Failure loads of restored abutments were close to or exceeded the maximum bite force of anterior teeth, and no differences were found among six groups (p > .05). Except TZ15Z and TZ0T group, the bending moment increased with the crown construction, especially for TZ30Z and TZ - 15Z groups (p < .001). CONCLUSIONS: The fracture strength of hybrid abutments restored with HTZ crown on Ti-Zr NDIs exceeded the bite forces of anterior teeth for all the groups and were not affected by the abutment angle. CLINICAL RELEVANCE: In terms of fracture strength, Ti-Zr NDIs combined with angulated hybrid abutments and HTZ crowns can be used in the anterior region.


Asunto(s)
Implantes Dentales , Circonio , Titanio , Ensayo de Materiales , Diseño de Implante Dental-Pilar , Pilares Dentales , Fracaso de la Restauración Dental , Análisis del Estrés Dental , Coronas
15.
Chemistry ; 29(15): e202203309, 2023 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-36509732

RESUMEN

1,3,5-tri-substituted benzene rings emerged with unique properties has widespread applications in materials, boosting the rapid development of their synthesis. Despite the significance, the direct construction of hetero-1,3,5-trisubstituted benzene core was far less-developed. Herein, we realized a DBU-mediated isomerization/6-π electro-cyclization/oxidative aromatization cascade of sulfonyl-substituted allenyl ketones under an air atmosphere (DBU=1,8-diazabicyclo[5.4.0]undec-7-ene). This versatile protocol featured metal-free conditions, easy operation, and broad functional group tolerance provides a new avenue for the construction of hetero-1,3,5-tri-substituted benzene.

16.
Stem Cells ; 41(2): 169-183, 2023 03 02.
Artículo en Inglés | MEDLINE | ID: mdl-36512434

RESUMEN

The apoptosis of grafted islets is an urgent problem due to the high rate of islet loss soon after transplantation. MicroRNA-21-5p (miR-21-5p) is an essential mediator of bone marrow mesenchymal stem cells-derived exosomes (BMSCs-Exo) during anti-apoptosis, but its effect and the underlying molecular mechanism in islet transplantation remain partially understood. Here, we found that miR-21-5p could be delivered to islet cells via BMSCs-Exo. Subsequently, we demonstrated that miR-21-5p overexpression reduced apoptosis in islets and INS-1 cells, whereas miR-21-5p inhibition enhanced apoptosis. A mechanistic analysis involving RNA sequencing and bioinformatic analysis was performed to determine the interaction between miR-21-5p and its target gene programmed cell death 4 (PDCD4), which was further verified by a dual luciferase assay. In vivo, the grafted islets overexpressing miR-21-5p showed a higher survival rate, better insulin secretion function, and a lower apoptosis rate. In conclusion, these results demonstrated that miR­21­5p from BMSCs-Exo protects against the apoptosis of grafted islets by inhibiting PDCD4 expression. Hence, miR-21-5p can be used as a cell-free therapeutic agent to minimize ß-cell apoptosis at the early stage of islet transplantation.


Asunto(s)
Exosomas , Trasplante de Islotes Pancreáticos , Islotes Pancreáticos , Células Madre Mesenquimatosas , MicroARNs , MicroARNs/genética , MicroARNs/metabolismo , Apoptosis/genética , Islotes Pancreáticos/metabolismo , Células Madre Mesenquimatosas/metabolismo , Exosomas/metabolismo
17.
Cell Mol Life Sci ; 79(10): 538, 2022 Oct 03.
Artículo en Inglés | MEDLINE | ID: mdl-36190571

RESUMEN

Early apoptosis of grafted islets is one of the main factors affecting the efficacy of islet transplantation. The combined transplantation of islet cells and bone marrow mesenchymal stem cells (BMSCs) can significantly improve the survival rate of grafted islets. Transcription factor insulin gene enhancer binding protein 1 (ISL1) is shown to promote the angiogenesis of grafted islets and the paracrine function of mesenchymal stem cells during the co-transplantation, yet the regulatory mechanism remains unclear. By using ISL1-overexpressing BMSCs and the subtherapeutic doses of islets for co-transplantation, we managed to reduce the apoptosis and improve the survival rate of the grafts. Our metabolomics and proteomics data suggested that ISL1 upregulates aniline (ANLN) and Inhibin beta A chain (INHBA), and stimulated the release of caffeine in the BMSCs. We then demonstrated that the upregulation of ANLN and INHBA was achieved by the binding of ISL1 to the promoter regions of the two genes. In addition, ISL1 could also promote BMSCs to release exosomes with high expression of ANLN, secrete INHBA and caffeine, and reduce streptozocin (STZ)-induced islets apoptosis. Thus, our study provides mechanical insight into the islet/BMSCs co-transplantation and paves the foundation for using conditioned medium to mimic the ISL1-overexpressing BMSCs co-transplantation.


Asunto(s)
Exosomas , Insulinas , Islotes Pancreáticos , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Compuestos de Anilina/metabolismo , Apoptosis/genética , Cafeína/metabolismo , Cafeína/farmacología , Medios de Cultivo Condicionados , Subunidades beta de Inhibinas , Insulinas/metabolismo , Islotes Pancreáticos/metabolismo , Células Madre Mesenquimatosas/metabolismo , Estreptozocina/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo
18.
J Environ Manage ; 320: 115833, 2022 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-35940011

RESUMEN

Green innovation activities of enterprises often fall into the dilemma of financing constraints. Hence, it is urgent that the financial system develops and becomes innovative, especially for a developing country like China. Existing literature mainly explores the influencing factors of green innovation from the environmental regulation, economic growth and government subsidies perspective. However, few papers critically study how digital finance influences green innovations. To explore the internal influencing mechanism of digital finance on the quantity and quality of green technology innovation, panel data of 271 prefecture-level cities from 2011 to 2019 in China is used. Based on theoretical analysis and empirical research, we get the following conclusions. First, digital finance can improve the quantity and quality of green technological innovation, which has become a significant driving force for green innovations in China. The results are still robust after the endogeneity tests. Second, the results of heterogeneous analysis indicate that the different dimensions of digital finance can improve green innovations. They include breadth of coverage, depth of use, and degree of digitization. The positive effect of digital finance is most substantial in eastern cities, followed by central cities, and weakest in western cities. Third, digital finance indirectly improves green innovation mainly by alleviating financing constraints. Our empirical results provide policy enlightenment for realizing the coordination of China's urban digital transformation and green economic development.


Asunto(s)
Desarrollo Económico , Invenciones , China , Ciudades
19.
Cell Mol Biol (Noisy-le-grand) ; 68(3): 51-58, 2022 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-35988194

RESUMEN

This study was to explore the mechanism of action of nanomaterial-loaded clarithromycin (CLA) after sinusitis surgery. Under the guidance of dynamic enhanced scanning (DES). 120 patients with sinusitis admitted to the First Affiliated Hospital of China Medical University from July 2019 to March 2020 were selected and divided into a control group and an observation group according to the random number table method, with 60 cases in each group. Then, the CLA-containing nano-polylactic acid material was prepared, observed with the scanning electron microscope (SEM), and its drug release ability was tested. All patients underwent endoscopic sinus surgery under general anesthesia. After the surgery was completed, patients in the control group were given only CLA capsules, and patients in the observation group were given freshly prepared nanomaterial-loaded CLA, and both groups of patients were continuously observed for two weeks. After that, the patients were examined using the dynamic enhancement computed tomography (CT). The clinical efficacy, serum interleukin-4 (IL-4), interleukin-8 (IL-8), and tumor necrosis factor α (TNF-α) levels of the two groups of patients were observed. The secretions of the patients' sinuses were performed with microbial bacterial culture, and the results were observed and recorded. Results showed that the characterization and analysis of the nano drug-carrying preparation suggested that the polylactic acid nanomembrane showed linear fiber morphology, relatively dense distribution, not greatly different fiber diameter, and small porosity. Characterization under a field of view (FOV) of 500 um showed that the fiber surface was smooth and rich in content. The release of CLA showed a gradual and steady upward trend. On the 25th day, nearly 50% of the dose had been released, and it had reached more than 90% of the total release on the 55th day. According to the statistics on the clinical efficacy of patients, it was found that the number of cured and effective patients in the observation group was higher than that of the control group, while the number of ineffective cases was much lower than that of the control group. The dynamic enhanced CT examination results of the patients in the control group after treatment showed that the soft tissue mass on the posterior right side of the nasopharynx was reduced, but the pharyngeal suture still existed; while those in the observation group showed that the plain scan density was uniform, and the mastoid air cells were clear on both sides. The number of cases with Staphylococcus aureus (S. aureus), Staphylococcus saprophyticus (S. saprophyticus), and Pasteurella multocida infections in the observation group were observably lower than those of the control group (P< 0.05), and it was the same case for the levels of serum IL-4, IL-8, and TNF-α. Conclusion: after dynamic enhanced CT scanning, it can be found that the nanomaterial-loaded CLA increased the utilization rate of the drug, showing good clinical efficacy, and effectively improved the clinical symptoms of patients, achieving the therapeutic effect.


Asunto(s)
Claritromicina , Sistema de Administración de Fármacos con Nanopartículas , Sinusitis , Claritromicina/farmacología , Claritromicina/uso terapéutico , Humanos , Interleucina-4 , Interleucina-8 , Sistema de Administración de Fármacos con Nanopartículas/farmacología , Sistema de Administración de Fármacos con Nanopartículas/uso terapéutico , Nanoestructuras/uso terapéutico , Sinusitis/tratamiento farmacológico , Sinusitis/cirugía , Staphylococcus aureus , Factor de Necrosis Tumoral alfa
20.
Chem Sci ; 13(11): 3169-3175, 2022 Mar 16.
Artículo en Inglés | MEDLINE | ID: mdl-35414881

RESUMEN

The modulation of selectivity of highly reactive carbon radical cross-coupling for the construction of C-C bonds represents a challenging task in organic chemistry. N-Heterocyclic carbene (NHC) catalyzed radical transformations have opened a new avenue for acyl radical cross-coupling chemistry. With this method, highly selective cross-coupling of an acyl radical with an alkyl radical for efficient construction of C-C bonds was successfully realized. However, the cross-coupling reaction of acyl radicals with vinyl radicals has been much less investigated. We herein describe NHC and visible light-mediated photoredox co-catalyzed radical 1,4-sulfonylacylation of 1,3-enynes, providing structurally diversified valuable tetrasubstituted allenyl ketones. Mechanistic studies indicated that ketyl radicals are formed from aroyl fluorides via the oxidative quenching of the photocatalyst excited state, allenyl radicals are generated from chemo-specific sulfonyl radical addition to the 1,3-enynes, and finally, the key allenyl and ketyl radical cross-coupling provides tetrasubstituted allenyl ketones.

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