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1.
Exp Cell Res ; 432(2): 113794, 2023 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-37741491

RESUMEN

Low back pain (LBP) is the leading cause of disability worldwide, with a strong correlation to intervertebral disc degeneration (IDD). Inflammation-induced extracellular matrix (ECM) degradation plays a major role in IDD's progression. Emodin, known for its anti-inflammatory effects and ability to inhibit ECM degradation in osteoarthritis, but its role in IDD is unclear. Our study aimed to explore emodin's role and mechanisms on IDD both in vivo and in vitro. We discovered that emodin positively regulated anabolic markers (COL2A1, aggrecan) and negatively impacted catabolic markers (MMP3, MMP13) in nucleus pulposus cells, while also inhibiting cell apoptosis under inflammation environment. We revealed that emodin inhibits inflammation-induced NF-ĸB activation by suppressing the degradation of LRP1 via the proteasome pathway. Additionally, LRP1 was validated as essential to emodin's regulation of ECM metabolism and apoptosis, both in vitro and in vivo. Ultimately, we demonstrated that emodin effectively alleviates IDD in a rat model. Our findings uncover the novel pathway of emodin inhibiting ECM degradation and apoptosis through the inhibition of NF-κB via LRP1, thus alleviating IDD. This study not only broadens our understanding of emodin's role and mechanism in IDD treatment but also guides future therapeutic interventions.

2.
BMC Biol ; 21(1): 192, 2023 09 12.
Artículo en Inglés | MEDLINE | ID: mdl-37697363

RESUMEN

BACKGROUND: Lauraceae is well known for its significant phylogenetic position as well as important economic and ornamental value; however, most evergreen species in Lauraceae are restricted to tropical regions. In contrast, camphor tree (Cinnamomum camphora) is the most dominant evergreen broadleaved tree in subtropical urban landscapes. RESULTS: Here, we present a high-quality reference genome of C. camphora and conduct comparative genomics between C. camphora and C. kanehirae. Our findings demonstrated the significance of key genes in circadian rhythms and phenylpropanoid metabolism in enhancing cold response, and terpene synthases (TPSs) improved defence response with tandem duplication and gene cluster formation in C. camphora. Additionally, the first comprehensive catalogue of C. camphora based on whole-genome resequencing of 75 accessions was constructed, which confirmed the crucial roles of the above pathways and revealed candidate genes under selection in more popular C. camphora, and indicated that enhancing environmental adaptation is the primary force driving C. camphora breeding and dominance. CONCLUSIONS: These results decipher the dominance of C. camphora in subtropical urban landscapes and provide abundant genomic resources for enlarging the application scopes of evergreen broadleaved trees.


Asunto(s)
Cinnamomum camphora , Cinnamomum camphora/genética , Filogenia , Fitomejoramiento , Análisis de Secuencia de ADN , Genómica
3.
J Exp Bot ; 74(4): 1275-1290, 2023 02 13.
Artículo en Inglés | MEDLINE | ID: mdl-36433929

RESUMEN

Jasminum sambac is a well-known plant for its attractive and exceptional fragrance, the flowers of which are used to produce scented tea. Jasmonate (JA), an important plant hormone was first identified in Jasminum species. Jasmine plants contain abundant JA naturally, of which the molecular mechanisms of synthesis and accumulation are not clearly understood. Here, we report a telomere-to-telomere consensus assembly of a double-petal J. sambac genome along with two haplotype-resolved genomes. We found that gain-and-loss, positive selection, and allelic specific expression of aromatic volatile-related genes contributed to the stronger flower fragrance in double-petal J. sambac compared with single- and multi-petal jasmines. Through comprehensive comparative genomic, transcriptomic, and metabolomic analyses of double-petal J. sambac, we revealed the genetic basis of the production of aromatic volatiles and salicylic acid (SA), and the accumulation of JA under non-stress conditions. We identified several key genes associated with JA biosynthesis, and their non-stress related activities lead to extraordinarily high concentrations of JA in tissues. High JA synthesis coupled with low degradation in J. sambac results in accumulation of high JA under typical environmental conditions, similar to the accumulation mechanism of SA. This study offers important insights into the biology of J. sambac, and provides valuable genomic resources for further utilization of natural products.


Asunto(s)
Jasminum , Jasminum/genética , Perfilación de la Expresión Génica , Transcriptoma , Odorantes
4.
Int Orthop ; 47(3): 793-801, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36352306

RESUMEN

BACKGROUND: Although enormous studies have been devoted to solving the problem of intervertebral disc degeneration/herniation, little attention is paid to the effect of paraspinal muscles on it. We aimed to investigate the correlation between paraspinal muscle atrophy and lumbar disc degeneration to recognize paraspinal muscle atrophy and its importance to the spine. PATIENTS AND METHODS: A total of 107 patients were enrolled in the study (65 females, 42 males; age 50.87 ± 15.391 years old). Cross-sectional area, functional cross-sectional area, and fatty infiltration of the posterior paraspinal muscles were measured at the level of L4/5, and the degree of facet joint degeneration was evaluated at the levels of L3/4, L4/5, and L5/S1 by MRI. After controlling the confounding factors by multiple linear regression, the correlations among paraspinal muscle atrophy, disc degeneration, and facet joint degeneration were analyzed. Meanwhile, Pearson/Spearson rank analysis was used to analyze the correlation between clinical symptoms (VAS and ODI) and paraspinal muscle atrophy. RESULTS: There was a strong correlation between paraspinal muscle atrophy and disc degeneration after controlling the confounding factors (p < 0.05, R > 0.5). There was a weak correlation between paraspinal muscle atrophy and facet joint degeneration (p < 0.05, R < 0.5). There was a significant correlation between facet joint degeneration and intervertebral disc degeneration (p < 0.05, R > 0.7). The fatty infiltration of paraspinal muscle was weakly correlated with ODI (p < 0.05, R < 0.3), but VAS was not. CONCLUSIONS: The degree of paraspinal muscle atrophy increased with lumbar disc degeneration and facet joint degeneration and fatty infiltration of multifidus was more susceptible to weight.


Asunto(s)
Degeneración del Disco Intervertebral , Desplazamiento del Disco Intervertebral , Disco Intervertebral , Dolor de la Región Lumbar , Espondilosis , Masculino , Femenino , Humanos , Adulto , Persona de Mediana Edad , Anciano , Degeneración del Disco Intervertebral/complicaciones , Degeneración del Disco Intervertebral/diagnóstico por imagen , Músculos Paraespinales/diagnóstico por imagen , Dolor de la Región Lumbar/etiología , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/patología , Atrofia Muscular/etiología , Imagen por Resonancia Magnética
5.
J Am Chem Soc ; 142(41): 17693-17702, 2020 10 14.
Artículo en Inglés | MEDLINE | ID: mdl-32941025

RESUMEN

The selective installation of azide groups into C(sp3)-H bonds is a priority research topic in organic synthesis, particularly in pharmaceutical discovery and late-stage diversification. Herein, we demonstrate a generalized manganese-catalyzed oxidative azidation methodology of C(sp3)-H bonds using nucleophilic NaN3 as an azide source under electrophotocatalytic conditions. This approach allows us to perform the reaction without the necessity of adding an excess of the substrate and successfully avoiding the use of stoichiometric chemical oxidants such as iodine(III) reagent or NFSI. A series of tertiary and secondary benzylic C(sp3)-H, aliphatic C(sp3)-H, and drug-molecule-based C(sp3)-H bonds in substrates are well tolerated under our protocol. The simultaneous gram-scale synthesis and the ease of transformation of azide to amine collectively advocate for the potential application in the preparative synthesis. Good reactivity of the tertiary benzylic C(sp3)-H bond and selectivity of the tertiary aliphatic C(sp3)-H bond in substrates to incorporate nitrogen-based functionality at the tertiary alkyl group also provide opportunities to manipulate numerous potential medicinal candidates. We anticipate our synthetic protocol, consisting of metal catalysis, electrochemistry, and photochemistry, would provide a new sustainable option to execute challenging organic synthetic transformations.

6.
Molecules ; 25(16)2020 Aug 11.
Artículo en Inglés | MEDLINE | ID: mdl-32796612

RESUMEN

Rapid growth in the world's economy depends on a significant increase in energy consumption. As is known, most of the present energy supply comes from coal, oil, and natural gas. The overreliance on fossil energy brings serious environmental problems in addition to the scarcity of energy. One of the most concerning environmental problems is the large contribution to global warming because of the massive discharge of CO2 in the burning of fossil fuels. Therefore, many efforts have been made to resolve such issues. Among them, the preparation of valuable fuels or chemicals from greenhouse gas (CO2) has attracted great attention because it has made a promising step toward simultaneously resolving the environment and energy problems. This article reviews the current progress in CO2 conversion via different strategies, including thermal catalysis, electrocatalysis, photocatalysis, and photoelectrocatalysis. Inspired by natural photosynthesis, light-capturing agents including macrocycles with conjugated structures similar to chlorophyll have attracted increasing attention. Using such macrocycles as photosensitizers, photocatalysis, photoelectrocatalysis, or coupling with enzymatic reactions were conducted to fulfill the conversion of CO2 with high efficiency and specificity. Recent progress in enzyme coupled to photocatalysis and enzyme coupled to photoelectrocatalysis were specially reviewed in this review. Additionally, the characteristics, advantages, and disadvantages of different conversion methods were also presented. We wish to provide certain constructive ideas for new investigators and deep insights into the research of CO2 conversion.


Asunto(s)
Dióxido de Carbono/química , Fuentes Generadoras de Energía , Combustibles Fósiles/análisis , Efecto Invernadero , Conservación de los Recursos Naturales , Fotosíntesis
7.
J Cell Physiol ; 234(11): 20432-20442, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31012109

RESUMEN

Emerging evidence shows that rheumatoid arthritis (RA) progression can be induced by the activation of Toll-like receptor (TLR) signaling pathway. Regulator of G-protein signaling 1 (RGS1) is observed to be a candidate biomarker for arthritis. Accordingly, the present study aims to determine the potential effects of RGS1 mediating TLR on RA. A rat model of collagen-induced arthritis (CIA) was established to mimic the features of RA by injection of bovine type II collagen. The rats with CIA were treated with short hairpin RNA (shRNA) against RGS1 or TLR pathway activator Poly I:C to elucidate the role of RGS1 in RA progression. The inflammatory factors were measured, and the thoracic gland and spleen indexes as well as the vascular density were determined. The expression levels of RGS1, TLR3, vascular endothelial growth factor (VEGF), metalloproteinase-2 (MMP-2), MMP-9, and interleukin 1 receptor-associated kinase-4 (IRAK4) were determined. RGS1 was robustly increased in RA. The TLR signaling pathway was suppressed by RGS1 silencing. shRNA-mediated depletion of RGS1 was shown to significantly enhance thoracic gland index and inhibit the serum levels of TNF-α, IL-1ß, and IL-17, spleen index, vascular density, and the expression levels of TLR3, VEGF, MMP-2, MMP-9, and IRAK4. However, when the rats with CIA were treated with Poly I:C, the trend of effects was opposite. These findings highlight that functional suppression of RGS1 inhibits the inflammatory response and angiogenesis by inactivating the TLR signaling pathway in rats with CIA, thereby providing a novel therapeutic target for RA treatment.


Asunto(s)
Artritis Reumatoide/genética , Neovascularización Patológica/genética , Proteínas RGS/genética , Receptores Toll-Like/efectos de los fármacos , Animales , Artritis Experimental/tratamiento farmacológico , Artritis Reumatoide/tratamiento farmacológico , Células Cultivadas , Colágeno Tipo II/metabolismo , Fibroblastos/metabolismo , Humanos , Metaloproteinasa 2 de la Matriz/metabolismo , Neovascularización Patológica/tratamiento farmacológico , Ratas Wistar , Receptores Toll-Like/metabolismo
8.
Int J Mol Sci ; 20(19)2019 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-31569708

RESUMEN

Male-sterile plants provide an important breeding tool for the heterosis of hybrid crops, such as Brassicaceae. In the last decade, circular RNAs (circRNAs), as a novel class of covalently closed and single-stranded endogenous non-coding RNAs (ncRNAs), have received much attention because of their functions as "microRNA (miRNA) sponges" and "competing endogenous RNAs" (ceRNAs). However, the information about circRNAs in the regulation of male-sterility and anther development is limited. In this study, we established the Polima cytoplasm male sterility (CMS) line "Bcpol97-05A", and the fertile line, "Bcajh97-01B", in Brassica campestris L. ssp. chinensis Makino, syn. B. rapa ssp. chinensis, and performed RNA expression profiling comparisons between the flower buds of the sterile line and fertile line by whole-transcriptome sequencing. A total of 31 differentially expressed (DE) circRNAs, 47 DE miRNAs, and 4779 DE mRNAs were identified. By using Cytoscape, the miRNA-mediated regulatory network and ceRNA network were constructed, and the circRNA A02:23507399|23531438 was hypothesized to be an important circRNA regulating anther development at the post-transcriptional level. The gene ontology (GO) analysis demonstrated that miRNAs and circRNAs could regulate the orderly secretion and deposition of cellulose, sporopollenin, pectin, and tryphine; the timely degradation of lipids; and the programmed cell death (PCD) of tapetum cells, which play key roles in anther development. Our study revealed a new circRNA-miRNA-mRNA network, which is involved in the anther development of B. campestris, which enriched the understanding of CMS in flowering plants, and laid a foundation for further study on the functions of circRNAs and miRNAs during anther development.


Asunto(s)
Brassica/genética , Flores/genética , Regulación de la Expresión Génica de las Plantas , MicroARNs/genética , ARN Circular/genética , ARN Mensajero/genética , Transcriptoma , Redes Reguladoras de Genes , Fenotipo , Desarrollo de la Planta/genética
9.
Microbiology (Reading) ; 164(9): 1146-1155, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-30024369

RESUMEN

The synthesis of methionine is critical for most bacteria. It is known that cellular methionine has a feedback effect on the expression of met genes involved in de novo methionine biosynthesis. Previous studies revealed that Gram-negative bacteria control met gene expression at the transcriptional level by regulator proteins, while most Gram-positive bacteria regulate met genes at post-transcriptional level by RNA regulators (riboregulators) located in the 5'UTR of met genes. However, despite its importance, the methionine biosynthesis pathway in the Gram-negative Xanthomonas genus that includes many important plant pathogens is completely uncharacterized. Here, we address this issue using the crucifer black rot pathogen Xanthomonas campestris pv. campestris (Xcc), a model bacterium in microbe-plant interaction studies. The work identified an operon (met) involved in de novo methionine biosynthesis in Xcc. Disruption of the operon resulted in defective growth in methionine-limited media and in planta. Western blot analysis revealed that the expression of the operon is dependent on methionine levels. Further molecular analyses demonstrated that the 5'UTR, but not the promoter of the operon, is involved in feedback regulation on operon expression in response to methionine availability, providing an example of a Gram-negative bacterium utilizing a 5'UTR region to control the expression of the genes involved in methionine biosynthesis.


Asunto(s)
Regiones no Traducidas 5' , Retroalimentación Fisiológica , Regulación Bacteriana de la Expresión Génica , Metionina/biosíntesis , Xanthomonas campestris/metabolismo , Eliminación de Gen , Perfilación de la Expresión Génica , Operón , Xanthomonas campestris/genética , Xanthomonas campestris/crecimiento & desarrollo
11.
Materials (Basel) ; 17(5)2024 Feb 22.
Artículo en Inglés | MEDLINE | ID: mdl-38473485

RESUMEN

The effect of structure on the vibration response was explored for four piano soundboards with different but commonly adopted structures. The vibration response was obtained using the free-vibration method, and the values of the dynamic modulus of elasticity and dynamic shear modulus obtained using the free-vibration frequency method (EF and GF) were compared with the dynamic modulus of elasticity obtained using the Euler beam method (EE) and dynamic shear modulus obtained using the free-plate torsional vibration method (GT), respectively. It was found that the soundboards with different structures had different vibration modes and that excitation at different locations highlighted different vibration modes. For all the soundboards analyzed, the EE and GT were higher than EF and GF by 2.2% and 24.3%, respectively. However, the trends of the results of these methods were the same. The four piano soundboards with different structures possessed varying dynamic moduli of elasticity and dynamic shear moduli. These rules are consistent with the grain directions of the soundboards and the anisotropy of the wood (the direction of the units of the soundboards). The results show that the vibration mode of the piano soundboard is complex. The dynamic elastic modulus of the soundboard can be calculated using the Euler beam method. The results provide a reference for studies on the vibration response, material selection, production technology, and testing of piano soundboards.

12.
Materials (Basel) ; 17(3)2024 Jan 23.
Artículo en Inglés | MEDLINE | ID: mdl-38591404

RESUMEN

As protective coatings for the thermal parts of aero-engines, AlCoCrFeNi coatings have good application prospects. In this study, atmospheric plasma spraying (APS) was used to prepare AlCoCrFeNi high-entropy coatings (HECs), which were oxidized from 650 °C to 1000 °C. The mechanism of the oxide layer formation and the internal phase transition were systematically investigated. The results show that a mixed oxide scale with a laminated structure was formed at the initial stage of oxidation. The redistribution of elements and phase transition occurred in the HECs' matrix; the BCC/B2 structure transformed to Al-Ni ordered B2 phase and Fe-Cr disordered A2 phase.

13.
J Med Chem ; 67(11): 9091-9103, 2024 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-38778566

RESUMEN

Induction of cuproptosis and targeting of multiple signaling pathways show promising applications in tumor therapy. In this study, we synthesized two thiosemicarbazone-copper complexes ([CuII(L)Cl] 1 and [CuII2CuI(L)2Cl3] 2, where HL is the (E)-N-methyl-2-(phenyl(pyridin-2-yl)methylene ligand), to assess their antilung cancer activities. Both copper complexes showed better anticancer activity than cisplatin and exhibited hemolysis comparable to that of cisplatin. In vivo experiments showed that complex 2 retarded the A549 cell growth in a mouse xenograft model with low systemic toxicity. Primarily, complex 2 kills lung cancer cells in vitro and in vivo by triggering multiple pathways, including cuproptosis. Complex 2 is the first mixed-valent Cu(I/II) complex to induce cellular events consistent with cuproptosis in cancer cells, which may stimulate the development of mixed-valent copper complexes and provide effective cancer therapy.


Asunto(s)
Antineoplásicos , Complejos de Coordinación , Cobre , Neoplasias Pulmonares , Tiosemicarbazonas , Tiosemicarbazonas/química , Tiosemicarbazonas/farmacología , Tiosemicarbazonas/síntesis química , Tiosemicarbazonas/uso terapéutico , Humanos , Cobre/química , Animales , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Antineoplásicos/uso terapéutico , Complejos de Coordinación/farmacología , Complejos de Coordinación/química , Complejos de Coordinación/síntesis química , Complejos de Coordinación/uso terapéutico , Ratones , Ratones Desnudos , Adenocarcinoma del Pulmón/tratamiento farmacológico , Adenocarcinoma del Pulmón/patología , Línea Celular Tumoral , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/patología , Células A549 , Proliferación Celular/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto , Transducción de Señal/efectos de los fármacos , Relación Estructura-Actividad , Hemólisis/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Ratones Endogámicos BALB C
14.
Cell Prolif ; : e13696, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38952035

RESUMEN

N6-methyladenosine (m6A) exerts essential roles in early embryos, especially in the maternal-to-zygotic transition stage. However, the landscape and roles of RNA m6A modification during the transition between pluripotent stem cells and 2-cell-like (2C-like) cells remain elusive. Here, we utilised ultralow-input RNA m6A immunoprecipitation to depict the dynamic picture of transcriptome-wide m6A modifications during 2C-like transitions. We found that RNA m6A modification was preferentially enriched in zygotic genome activation (ZGA) transcripts and MERVL with high expression levels in 2C-like cells. During the exit of the 2C-like state, m6A facilitated the silencing of ZGA genes and MERVL. Notably, inhibition of m6A methyltransferase METTL3 and m6A reader protein IGF2BP2 is capable of significantly delaying 2C-like state exit and expanding 2C-like cells population. Together, our study reveals the critical roles of RNA m6A modification in the transition between 2C-like and pluripotent states, facilitating the study of totipotency and cell fate decision in the future.

15.
Int J Mol Sci ; 14(3): 5806-16, 2013 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-23481641

RESUMEN

Lung cancer is the most common cause of cancer-related death. Nonetheless, a decrease in overall incidence and mortality has been observed in the last 30 years due to prevention strategies and improvements in the use of chemotherapeutic agents. In recent studies, Simvastatin (SIM) has demonstrated anti-tumor activity, as well as potent chemopreventive action. As an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA), SIM has been shown to stimulate apoptotic cell death. In this study, an MTT assay revealed the cytotoxic activity of SIM against human large cell lung cancer (Non-small cell lung cancer; NSCLC) cells (NCI-H460); however, induced apoptosis was not observed in NCI-H460 cells. Protein expression levels of cell cycle regulating proteins Cdk4, Cyclin D1, p16 and p27 were markedly altered by SIM. Collectively, our results indicate that SIM inhibits cell proliferation and arrests NCI-H460 cell cycle progression via inhibition of cyclin-dependent kinases and cyclins and the enhancement of CDK inhibitors p16 and p27. Our findings suggest that, in addition to the known effects on hypercholesterolemia therapy, SIM may also provide antitumor activity in established NSCLC.

16.
NPJ Precis Oncol ; 7(1): 62, 2023 Jun 29.
Artículo en Inglés | MEDLINE | ID: mdl-37386055

RESUMEN

Postoperative recurrence and metastasis are the main reasons for the poor prognosis of osteosarcoma (OS). Currently, an ideal predictor for not only prognosis but also drug sensitivity and immunotherapy responses in OS patients is urgently needed. Angiogenesis plays a crucial role in tumour progression, which suggests its immense potential for predicting prognosis and responses to immunotherapy for OS. Angiogenesis patterns in OS were explored in depth in this study to construct a prognostic model called ANGscore and clarify the underlying mechanism involved in the immune microenvironment. The efficacy and robustness of the model were validated in multiple datasets, including bulk RNA-seq datasets (TARGET-OS, GSE21257), a single-cell RNA-seq dataset (GSE152048) and immunotherapy-related datasets (GSE91061, GSE173839). OS patients with a high ANGscore had a worse prognosis, accompanied by the immune desert phenotype. Pseudotime and cellular communication analyses in scRNA-seq data revealed that as the ANGscore increased, the malignant degree of cells increased, and IFN-γ signalling was involved in tumour progression and regulation of the tumour immune microenvironment. Furthermore, the ANGscore was associated with immune cell infiltration and the response rate to immunotherapy. OS patients with high ANGscore might be resistant to uprosertib, and be sensitive to VE821, AZD6738 and BMS.345541. In conclusion, we established a novel ANGscore system by comprehensively analysing the expression pattern of angiogenesis genes, which can accurately differentiate the prognosis and immune characteristics of OS populations. Additionally, the ANGscore can be used for patient stratification during immunotherapy, and guide individualized treatment strategies.

17.
Arthritis Res Ther ; 25(1): 45, 2023 03 21.
Artículo en Inglés | MEDLINE | ID: mdl-36945021

RESUMEN

BACKGROUND: Intervertebral disc degeneration (IDD) is one of the most common disorders related to the spine. Inflammation, apoptosis and extracellular matrix (ECM) degradation contribute to disc degeneration in nucleus pulposus cells (NPCs). This study focused on the role and mechanism of the p38 inhibitor TAK-715 in intervertebral disc degeneration. METHODS: NPCs were treated with IL-1ß to mimic apoptosis, followed by the addition of TAK-715. It was determined that apoptosis, inflammatory mediators (COX-2), inflammatory cytokines (HMGB1), and ECM components (collagen II, MMP9, ADAMTS5, and MMP3) existed in NPCs. In addition, the p38MAPK signaling pathways were examined. The role of TAK-715 in vivo was determined by acupuncture-induced intervertebral disc degeneration. Following an intradiscal injection of TAK-715, MRI and a histopathological analysis were conducted to assess the degree of degeneration. RESULTS: IL-1ß-induced apoptosis was alleviated by TAK-715 in vitro, and antiapoptotic proteins were upregulated. Furthermore, TAK-715 blocked IL-1ß-induced inflammatory mediator production (COX-2) and inflammatory cytokine production (HMGB1) and degraded the ECM (collagen II, MMP9, ADAMTS5, and MMP3). By inhibiting the phosphorylation of p38, TAK-715 exerted its effects. In a rat tail model, TAK-715 ameliorates puncture-induced disc degeneration based on MRI and histopathology evaluations. CONCLUSION: TAK-715 attenuated intervertebral disc degeneration in vitro and in vivo, suggesting that it might be an effective treatment for IDD.


Asunto(s)
Apoptosis , Benzamidas , Matriz Extracelular , Degeneración del Disco Intervertebral , Núcleo Pulposo , Animales , Ratas , Ciclooxigenasa 2/metabolismo , Proteína HMGB1/metabolismo , Disco Intervertebral/patología , Degeneración del Disco Intervertebral/tratamiento farmacológico , Metaloproteinasa 3 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Núcleo Pulposo/citología , Núcleo Pulposo/patología , Interleucina-1beta/farmacología , Matriz Extracelular/patología , Benzamidas/farmacología
18.
Biomed Pharmacother ; 165: 115040, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37364479

RESUMEN

Colorectal cancer (CRC) is one of highly prevalent cancer. Immunotherapy with immune checkpoint inhibitors (ICIs) has dramatically changed the landscape of treatment for many advanced cancers, but CRC still exhibits suboptimal response to immunotherapy. The gut microbiota can affect both anti-tumor and pro-tumor immune responses, and further modulate the efficacy of cancer immunotherapy, particularly in the context of therapy with ICIs. Therefore, a deeper understanding of how the gut microbiota modulates immune responses is crucial to improve the outcomes of CRC patients receiving immunotherapy and to overcome resistance in nonresponders. The present review aims to describe the relationship between the gut microbiota, CRC, and antitumor immune responses, with a particular focus on key studies and recent findings on the effect of the gut microbiota on the antitumor immune activity. We also discuss the potential mechanisms by which the gut microbiota influences host antitumor immune responses as well as the prospective role of intestinal flora in CRC treatment. Furthermore, the therapeutic potential and limitations of different modulation strategies for the gut microbiota are also discussed. These insights may facilitate to better comprehend the interplay between the gut microbiota and the antitumor immune responses of CRC patients and provide new research pathways to enhance immunotherapy efficacy and expand the patient population that could be benefited by immunotherapy.


Asunto(s)
Neoplasias Colorrectales , Microbioma Gastrointestinal , Humanos , Inmunoterapia , Inhibidores de Puntos de Control Inmunológico , Neoplasias Colorrectales/terapia
19.
Stem Cell Reports ; 18(2): 449-462, 2023 02 14.
Artículo en Inglés | MEDLINE | ID: mdl-36638787

RESUMEN

Multiple chromatin modifiers associated with H3K9me3 play important roles in the transition from embryonic stem cells to 2-cell (2C)-like cells. However, it remains elusive how H3K9me3 is remodeled and its association with totipotency. Here, we integrated transcriptome and H3K9me3 profiles to conduct a detailed comparison of 2C embryos and 2C-like cells. Globally, H3K9me3 is highly preserved and H3K9me3 dynamics within the gene locus is not associated with gene expression change during 2C-like transition. Promoter-deposited H3K9me3 plays non-repressive roles in the activation of genes during 2C-like transition. In contrast, transposable elements, residing in the nearby regions of up-regulated genes, undergo extensive elimination of H3K9me3 and are tended to be induced in 2C-like transitions. Furthermore, a large fraction of trophoblast stem cell-specific enhancers undergo loss of H3K9me3 exclusively in MERVL+/Zscan4+ cells. Our study therefore reveals the unique H3K9me3 profiles of 2C-like cells, facilitating the further exploration of totipotency.


Asunto(s)
Células Madre Embrionarias , Trofoblastos , Elementos Transponibles de ADN , Células Madre Embrionarias/metabolismo , Histonas/metabolismo , Metilación
20.
Nanomaterials (Basel) ; 12(10)2022 May 18.
Artículo en Inglés | MEDLINE | ID: mdl-35630947

RESUMEN

Graphene-cellulose-polyethyleneimine aerogels (GA-MCC-PEI) were prepared using a simple, environmentally friendly method to remove anionic and cationic dyes in water. Graphene-cellulose hydrogels were prepared using a hydrothermal method and then immersed in a polyethyleneimine aqueous solution for 48 h to obtain graphene-cellulose-polyethyleneimine hydrogels, which were then freeze-dried. The light and porous composite aerogels had a good compression resistance, and the maximum allowable pressure of the graphene-cellulose-polyethyleneimine aerogel with a cellulose content of 43% was 21.76 kPa, which was 827 times its weight. Adsorption of the anionic dye amaranth and the cationic dye methylene blue by the graphene-cellulose-polyethyleneimine aerogel was satisfactorily modeled using the Langmuir isothermal equation, indicating monolayer adsorption. When the cellulose content was 39%, the equilibrium adsorption capacities of the composite aerogel for amaranth and methylene blue were 369.37 mg/g and 237.33 mg/g, respectively. This graphene-cellulose-polyethyleneimine aerogel can be used to remove dye pollutants in water to maintain ecological balance, thus broadening the application space of aerogel materials, that is, as adsorbents in different environments.

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