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1.
Signal Transduct Target Ther ; 9(1): 80, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38565536

RESUMO

RNA-binding proteins (RBPs)-RNA networks have contributed to cancer development. Circular RNAs (circRNAs) are considered as protein recruiters; nevertheless, the patterns of circRNA-protein interactions in colorectal cancer (CRC) are still lacking. Processing bodies (PBs) formed through liquid-liquid phase separation (LLPS) are membrane-less organelles (MLOs) consisting of RBPs and RNA. Previous evidence suggests a connection between PBs dynamics and cancer progression. Despite the increasingly acknowledged crucial role of RBPs and RNA in the accumulation and maintenance of MLOs, there remains a lack of specific research on the interactions between PBs-related RBPs and circRNAs in CRC. Herein, we identify that MEX-3 RNA binding family member A (MEX3A), frequently upregulated in CRC tissues, predicts poorer patient survival. Elevated MEX3A accelerates malignance and inhibits autophagy of CRC cells. Importantly, MEX3A undergoes intrinsically disordered regions (IDRs)-dependent LLPS in the cytoplasm. Specifically, circMPP6 acts as a scaffold to facilitate the interaction between MEX3A and PBs proteins. The MEX3A/circMPP6 complex modulates PBs dynamic and promotes UPF-mediated phosphodiesterase 5A (PDE5A) mRNA degradation, consequently leading to the aggressive properties of CRC cells. Clinically, CRC patients exhibiting high MEX3A expression and low PDE5A expression have the poorest overall survival. Our findings reveal a collaboration between MEX3A and circMPP6 in the regulation of mRNA decay through triggering the PBs aggregation, which provides prognostic markers and/or therapeutic targets for CRC.


Assuntos
Neoplasias Colorretais , RNA Circular , Humanos , Autofagia/genética , Neoplasias Colorretais/metabolismo , Família , Fosfoproteínas/metabolismo , Proteínas/metabolismo , RNA/genética , RNA Circular/genética , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo
2.
Zhongguo Dang Dai Er Ke Za Zhi ; 26(4): 385-393, 2024 Apr 15.
Artigo em Chinês | MEDLINE | ID: mdl-38660903

RESUMO

OBJECTIVES: To investigate the effect of chaperone-mediated autophagy (CMA) on the damage of mouse microglial BV2 cells induce by unconjugated bilirubin (UCB). METHODS: The BV2 cell experiments were divided into two parts. (1) For the CMA activation experiment: control group (treated with an equal volume of dimethyl sulfoxide), QX77 group (treated with 20 µmol/L QX77 for 24 hours), UCB group (treated with 40 µmol/L UCB for 24 hours), and UCB+QX77 group (treated with both 20 µmol/L QX77 and 40 µmol/L UCB for 24 hours). (2) For the cell transfection experiment: LAMP2A silencing control group (treated with an equal volume of dimethyl sulfoxide), LAMP2A silencing control+UCB group (treated with 40 µmol/L UCB for 24 hours), LAMP2A silencing group (treated with an equal volume of dimethyl sulfoxide), and LAMP2A silencing+UCB group (treated with 40 µmol/L UCB for 24 hours). The cell viability was assessed using the modified MTT method. The expression levels of p65, nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), and cysteinyl aspartate specific proteinase-1 (caspase-1) were detected by Western blot. The relative mRNA expression levels of the inflammatory cytokines interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α (TNF-α) were determined by real-time quantitative polymerase chain reaction. Levels of IL-6 and TNF-α in the cell culture supernatant were measured using ELISA. The co-localization of heat shock cognate protein 70 with p65 and NLRP3 was detected by immunofluorescence. RESULTS: Compared to the UCB group, the cell viability in the UCB+QX77 group increased, and the expression levels of inflammation-related proteins p65, NLRP3, and caspase-1, as well as the mRNA relative expression levels of IL-1ß, IL-6, and TNF-α and levels of IL-6 and TNF-α decreased (P<0.05). Compared to the control group, there was co-localization of heat shock cognate protein 70 with p65 and NLRP3 in both the UCB and UCB+QX77 groups. After silencing the LAMP2A gene, compared to the LAMP2A silencing control+UCB group, the LAMP2A silencing+UCB group showed increased expression levels of inflammation-related proteins p65, NLRP3, and caspase-1, as well as increased mRNA relative expression levels of IL-1ß, IL-6, and TNF-α and levels of IL-6 and TNF-α (P<0.05). CONCLUSIONS: CMA is inhibited in UCB-induced BV2 cell damage, and activating CMA may reduce p65 and NLRP3 protein levels, suppress inflammatory responses, and counteract bilirubin neurotoxicity.


Assuntos
Bilirrubina , Autofagia Mediada por Chaperonas , Microglia , Animais , Camundongos , Microglia/metabolismo , Autofagia Mediada por Chaperonas/fisiologia , Autofagia Mediada por Chaperonas/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/fisiologia , Proteína 2 de Membrana Associada ao Lisossomo/genética , Proteína 2 de Membrana Associada ao Lisossomo/metabolismo , Caspase 1/genética , Caspase 1/metabolismo , Fator de Transcrição RelA/metabolismo , Fator de Transcrição RelA/genética , Fator de Necrose Tumoral alfa/metabolismo , Fator de Necrose Tumoral alfa/genética , Interleucina-1beta/metabolismo , Interleucina-1beta/genética , Interleucina-6/metabolismo , Interleucina-6/genética , Células Cultivadas , Sobrevivência Celular
3.
Cell Rep ; 43(1): 113654, 2024 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-38175757

RESUMO

Deficiency of DNA repair pathways drives the development of colorectal cancer. However, the role of the base excision repair (BER) pathway in colorectal cancer initiation remains unclear. This study shows that Nei-like DNA glycosylase 1 (NEIL1) is highly expressed in colorectal cancer (CRC) tissues and associated with poorer clinical outcomes. Knocking out neil1 in mice markedly suppresses tumorigenesis and enhances infiltration of CD8+ T cells in intestinal tumors. Furthermore, NEIL1 directly forms a complex with SATB2/c-Myc to enhance the transcription of COL17A1 and subsequently promotes the production of immunosuppressive cytokines in CRC cells. A NEIL1 peptide suppresses intestinal tumorigenesis in ApcMin/+ mice, and targeting NEIL1 demonstrates a synergistic suppressive effect on tumor growth when combined with a nuclear factor κB (NF-κB) inhibitor. These results suggest that combined targeting of NEIL1 and NF-κB may represent a promising strategy for CRC therapy.


Assuntos
Neoplasias Colorretais , DNA Glicosilases , Animais , Camundongos , Carcinogênese , Linfócitos T CD8-Positivos/metabolismo , Neoplasias Colorretais/genética , DNA Glicosilases/metabolismo , Reparo do DNA , NF-kappa B/metabolismo
4.
Exp Gerontol ; 183: 112322, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37929293

RESUMO

BACKGROUND: Severe sarcopenia may result in severe disability. Early diagnosis is currently the key to enhancing the treatment of sarcopenia, and there is an urgent need for a highly sensitive and dependable tool to evaluate the course of early sarcopenia in clinical practice. This study aims to investigate longitudinally the early diagnosability of magnetic resonance imaging (MRI)-based fat infiltration and blood flow perfusion technology in sarcopenia progression. METHODS: 48 Sprague-Dawley rats were randomly assigned into six groups that were based on different periods of dexamethasone (DEX) injection (0, 2, 4, 6, 8, 10 days). Multimodal MRI was scanned to assess muscle mass. Grip strength and swimming exhaustion time of rats were measured to assess muscle strength and function. Immunofluorescence staining for CD31 was employed to assess skeletal muscle capillary formation, and western blot was used to detect vascular endothelial growth factor-A (VEGF-A) and muscle ring finger-1 (MuRF-1) protein expression. Subsequently, we analyzed the correlation between imaging and histopathologic parameters. A receiver operating characteristic (ROC) analysis was conducted to assess the effectiveness of quantitative MRI parameters for discriminating diagnosis in both pre- and post-modeling of DEX-induced sarcopenic rats. RESULTS: Significant differences were found in PDFF, R2* and T2 values on day 2 of DEX-induction compared to the control group, occurring prior to the MRI-CSA values and limb grip strength on day 6 of induction and swimming exhaustion time on day 8 of induction. There is a strong correlation between MRI-CSA with HE-CSA values (r = 0.67; p < 0.001), oil red O (ORO) area with PDFF (r = 0.67; p < 0.001), microvascular density (MVD) (r = -0.79; p < 0.001) and VEGF-A (r = -0.73; p < 0.001) with R2*, MuRF-1 with MRI-CSA (r = -0.82; p < 0.001). The AUC of PDFF, R2*, and T2 values used for modeling evaluation are 0.81, 0.93, and 0.98, respectively. CONCLUSION: Imaging parameters PDFF, R2*, and T2 can be used to sensitively evaluate early pathological changes in sarcopenia. The successful construction of a sarcopenia rat model can be assessed when PDFF exceeds 1.25, R2* exceeds 53.85, and T2 exceeds 33.88.


Assuntos
Sarcopenia , Ratos , Animais , Sarcopenia/diagnóstico por imagem , Sarcopenia/patologia , Fator A de Crescimento do Endotélio Vascular , Músculo Quadríceps/diagnóstico por imagem , Músculo Quadríceps/patologia , Ratos Sprague-Dawley , Imageamento por Ressonância Magnética/métodos , Perfusão , Diagnóstico Precoce
5.
Integr Cancer Ther ; 22: 15347354231188679, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37565358

RESUMO

BACKGROUND: Aromatase inhibitors (AIs) are recommended as the preferred therapy for postmenopausal women with hormone receptor-positive (HR+) breast cancer. As a result, aromatase inhibitor-associated musculoskeletal symptom (AIMSS) have become a major problem leading to therapy discontinuation and decreased quality of life in patients receiving adjuvant AIs treatment. Multiple therapies have been attempted, but have yielded limited clinical results. This study will be performed to determine whether acupoint thread embedding (ATE) combined with Wenshen Bugu Decoction can effectively treat AIMSS, so as to improve the AIs medication compliance of postmenopausal breast cancer patients. METHODS: This study will utilize a randomized, 2 parallel groups controlled trial design. A total of 128 eligible postmenopausal breast cancer women with AIMSS will be randomized to receive a 12-week treatment with Wenshen Bugu Decoction alone (control group) or in combination with ATE (treatment group) in a 1:1 ratio. The primary outcome will be the 12 week Brief Pain Inventory Worst Pain (BPI-WP) score. The secondary outcome measures will include response rate, Brief Pain Inventory-Short Form (BFI-SF), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Functional Assessment of Cancer Therapy-Endocrine Symptom (FACT-ES), Functional Assessment of Cancer Therapy-Breast (FACT-B), bone marrow density (BMD), blood markers of bone metabolite, Morisky medication adherence scale-8 (MMAS-8), credibility and expectancy, and survival outcomes. DISCUSSION: This trial may provide clinical evidence that ATE combined with Wenshen Bugu Decoction can be beneficial for treating AIMSS among postmenopausal breast cancer survivors. Our findings will be helpful to enhance the quality of life and reduce the occurrence of AIs withdrawal.


Assuntos
Inibidores da Aromatase , Neoplasias da Mama , Humanos , Feminino , Inibidores da Aromatase/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/complicações , Qualidade de Vida , Pontos de Acupuntura , Pós-Menopausa , Dor/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto
6.
Artigo em Inglês | MEDLINE | ID: mdl-37598457

RESUMO

Marsdenia tenacissima is a traditional Chinese medicinal plant used for treating cancer, and its main medicinal part is the stem. Considering the resource shortage of M. tenacissima, it is of great significance to improve its utilization efficiency. Steroids and caffeoylquinic acids, the two main components of M. tenacissima, are composed of several basic structures. Based on this rule, a novel strategy of combinatorics-based chemical characterization was proposed to analyze the constituents of roots, stems and leaves of M. tenacissima. Combinatorics was used to generate a compound library for structure alignment, which has the advantages of wide coverage and high specificity. Steroids are composed of four basic parts: core skeleton (C), substituent at position 11 (A), substituent at position 12 (B) and sugar moiety (S). Based on combinatorics, a compound library consisting of 1080 steroids was generated. Diagnostic neutral loss has been used to effectively predict the substituents at position 11 and 12 of steroids, including acetyl, 2-methylpropionyl, tigloyl, 2-methylbutyryl and benzoyl. As a result, 131, 131 and 99 components were detected from the roots, stems and leaves of M. tenacissima, respectively. Principal component analysis (PCA) was used to analyze the differences of roots, stems and leaves, and orthogonal partial least squares-discriminant analysis (OPLS-DA) was further applied to find differential components. Tenacissoside H, a critical indicator component for quality evaluation of the stem, has been proved to be a differential component between roots and stems. Notably, the relative content of tenacissoside H in the roots was significantly higher than that in the stems. The bioactivity comparison showed that roots, stems and leaves of M. tenacissima had similar scavenging activity on 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical. However, their α-glucosidase inhibitory activity was ranked as leaves > stems > roots. Therefore, besides stems, the other parts of M. tenacissima have potential medicinal value. This study not only helps to develop the resource of M. tenacissima, but also provides a paradigm for the research of other similar medicinal plants.


Assuntos
Marsdenia , Plantas Medicinais , Espectrometria de Massas em Tandem , Bioensaio , Cromatografia Líquida
7.
J Bone Miner Metab ; 41(5): 673-681, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37507596

RESUMO

INTRODUCTION: Observational studies demonstrated that the relationship between bone mineral density and oral diseases is mixed. To access the association between heel bone mineral density and various oral diseases, we conducted the Mendelian randomization analysis to explore the association. MATERIALS AND METHODS: Two-sample bidirectional Mendelian analysis was used to explore the relationship between heel bone mineral density and various oral diseases. The inverse-variance weighted (IVW) was used as the primary effect estimate, and various methods were applied to test the reliability and stability of the results, namely MR-Egger, weighted median, simple mode, and weighted mode. RESULTS: This study showed that there was a negative relationship between heel BMD and periodontitis when heel BMD was used as an exposure factor and periodontitis as an outcome factor (IVW OR = 0.85; 95% CI, 0.75-0.95; p = 0.005). Bidirectional Mendelian randomization showed that there was no statistically significant association between periodontitis and heel bone mineral density when chronic periodontitis was the exposure factor (p > 0.05). And there was no significant relationship between heel bone mineral density and other oral diseases (dental caries, diseases of pulp and periapical tissues, impacted teeth, cleft lip, and cleft palate, oral and oropharyngeal cancer) (p > 0.05). CONCLUSION: This study showed that there was a negative relationship between heel bone density and periodontitis, and the decrease in heel bone density could promote the occurrence of periodontitis. In addition, there was no statistically significant relationship between heel bone density and other oral diseases.


Assuntos
Cárie Dentária , Fraturas Ósseas , Humanos , Densidade Óssea/genética , Análise da Randomização Mendeliana , Reprodutibilidade dos Testes , Polimorfismo de Nucleotídeo Único
8.
Biochem Genet ; 61(6): 2382-2400, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37060482

RESUMO

Oil palm (Elaeis guineensis) is the most important tropical oil-bearing crop species worldwide. MADS-box proteins, which play crucial roles in plant growth and development and are involved in various physiological and biochemical processes, compose one of the largest families of plant transcription factors. In this study, 42 MADS-box genes were screened from the mesocarp transcriptome database of oil palm fruit, and their phylogenetic relationships with Arabidopsis thaliana MADS-box genes were analyzed. Based on the results, MADS-box genes from oil palm mesocarp were classified into four groups: MIKCc-type, MIKC*-type, Mα-type, and Mγ-type MADS-box genes. Members of the subfamilies were classified according to the presence of three specific protein motifs. To explore the differential expression of the MADS-box genes, the dynamic expression of all selected MADS-box genes in oil palm was measured by RNA-seq. The high expression of specific MADS-box genes in the mesocarp of oil palm during different developmental stages indicates that those genes may play important roles in the cell division of and metabolite accumulation in the fruit and could become important targets for fruit development and oil accumulation research in oil palm.


Assuntos
Arecaceae , Frutas , Frutas/metabolismo , Filogenia , Fatores de Transcrição/genética , Motivos de Aminoácidos , Arecaceae/genética , Arecaceae/metabolismo , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
9.
Drug Deliv ; 30(1): 2165736, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36628545

RESUMO

Delivery of drugs to special locations of ocular lesions, while minimizing systemic and local toxic effects, is recognized as a critical challenge in the ophthalmic practice. The special anatomy and physiology barriers within the eyeball entail effective drug delivery systems. Emerging attempts in drug delivery has led to developments in ocular iontophoresis, which acts as a noninvasive technology to enhance drug penetration using a small electric current. This technique offers greater flexibility to deliver desired drug dose in a controlled and tolerable manner. In previous studies, this technique has been testified to deliver antibiotics, corticoid, proteins and other gene drugs into the eye with the potency of treating or alleviating diverse ophthalmological diseases including uveitis, cataract, retinoblastoma, herpes simplex and cytomegalovirus retinitis (CMVR), etc. In this review, we will introduce the recent developments in iontophoresis device. We also summarize the latest progress in coulomb controlled iontophoresis (CCI), hydrogel ionic circuit (HIC) and EyeGate II delivery system (EGDS), as well as overview the potential toxicity of iontophoresis. We will discuss these factors that affect the efficacy of iontophoresis experiments, and focus on the latest progress in its clinical application in the treatment of eye diseases.


Assuntos
Oftalmopatias , Iontoforese , Humanos , Preparações Farmacêuticas/metabolismo , Iontoforese/métodos , Olho , Sistemas de Liberação de Medicamentos/métodos , Oftalmopatias/tratamento farmacológico
10.
Crit Rev Food Sci Nutr ; 63(8): 1119-1142, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-34342521

RESUMO

Polysaccharides present in grapes interact with wine sensory-active compounds (polyphenols and volatile compounds) via different mechanisms and can affect wine organoleptic qualities such as astringency, color and aroma. Studies on the role that grape polysaccharides play in wines are reviewed in this paper. First, the composition of grape polysaccharides and their changes during grape ripening, winemaking and aging are introduced. Second, different interaction mechanisms of grape polysaccharides and wine sensory-active compounds (flavanols, anthocyanins and volatiles) are introduced, and the possible effects on wine astringency, color and aroma caused by these interactions are illustrated. Finally, the control of the grape polysaccharide content in practice is discussed, including classical winemaking methods (applying different maceration enzymes, temperature control, co-fermentation, blending), modern vinification technologies (pulsed electric field, ultrasound treatment), and the development of new grape polysaccharide products.


Assuntos
Vitis , Vinho , Vinho/análise , Antocianinas/análise , Frutas/química , Polifenóis , Sensação , Polissacarídeos
11.
Mar Drugs ; 18(8)2020 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-32784629

RESUMO

Astaxanthin is a natural product gaining increasing attention due to its safety and anti-cancer properties. In this study, we investigated the mechanisms of the anti-cancer effects of astaxanthin on prostate cancer (PCa) cell lines using aggressive PCa DU145 cells. Also an instantaneous silenced cell line (si-STAT3) derived from DU145 and a control cell line (si-NK) were used for the MTT and colony formation assays to determine the role of astaxanthin in proliferation and colony formation abilities. Flow cytometry assays were used to detect the apoptosis of tumor cells. Migration and invasion assays detected the weakening of the respective abilities. Western blot and RT-PCR tests detected the levels of STAT3 protein and mRNA. Astaxanthin resulted in suppression of the proliferation of DU145 cells and the level of STAT3. The treatment of DU145 cells with astaxanthin decreased the cloning ability, increased the apoptosis percentage and weakened the abilities of migration and invasion of the cells. Furthermore, astaxanthin reduced the expression of STAT3 at protein and mRNA levels. The effects were enhanced when astaxanthin and si-STAT3 were combined. The results of animal experiments were consistent with the results in cells. Thus, astaxanthin inhibits the proliferation of DU145 cells by reducing the expression of STAT3.


Assuntos
Antineoplásicos/farmacologia , Neoplasias da Próstata/tratamento farmacológico , Fator de Transcrição STAT3/metabolismo , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Camundongos Nus , Invasividade Neoplásica , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Fator de Transcrição STAT3/genética , Transdução de Sinais , Carga Tumoral/efeitos dos fármacos , Xantofilas/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
12.
Plant Cell Rep ; 39(11): 1505-1516, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32804247

RESUMO

KEY MESSAGE: EgMADS21 regulates PUFA accumulation in oil palm. Oil palm (Elaeis guineensis Jacq.) is the most productive world oil crop, accounting for 36% of world plant oil production. However, the molecular mechanism of the transcriptional regulation of fatty acid accumulation and lipid synthesis in the mesocarp of oil palm by up- or downregulating the expression of genes involved in related pathways remains largely unknown. Here, an oil palm MADS-box gene, EgMADS21, was screened in a yeast one-hybrid assay using the EgDGAT2 promoter sequence as bait. EgMADS21 is preferentially expressed in early mesocarp developmental stages in oil palm fruit and presents a negative correlation with EgDGAT2 expression. The direct binding of EgMADS21 to the EgDGAT2 promoter was confirmed by electrophoretic mobility shift assay. Subsequently, transient expression of EgMADS21 in oil palm protoplasts revealed that EgMADS21 not only binds to the EgDGAT2 promoter but also negatively regulates the expression of EgDGAT2. Furthermore, EgMADS21 was stably overexpressed in transgenic oil palm embryoids by Agrobacterium-mediated transformation. In three independent transgenic lines, EgDGAT2 expression was significantly suppressed by the expression of EgMADS21. The content of linoleic acid (C18:2) in the three transgenic embryoids was significantly decreased, while that of oleic acid (C18:1) was significantly increased. Combined with the substrate preference of EgDGAT2 identified in previous research, the results demonstrate the molecular mechanism by which EgMADS21 regulates EgDGAT2 expression and ultimately affects fatty acid accumulation in the mesocarp of oil palm.


Assuntos
Arecaceae/genética , Arecaceae/metabolismo , Ácidos Graxos Insaturados/metabolismo , Proteínas de Plantas/genética , Diacilglicerol O-Aciltransferase/genética , Diacilglicerol O-Aciltransferase/metabolismo , Ácidos Graxos Insaturados/genética , Regulação da Expressão Gênica de Plantas , Proteínas de Domínio MADS/genética , Proteínas de Domínio MADS/metabolismo , Óleo de Palmeira/metabolismo , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas , Regiões Promotoras Genéticas , Protoplastos/metabolismo
13.
Cancer Manag Res ; 12: 3561-3569, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32547193

RESUMO

BACKGROUND: Cancer metastasis is the main obstacle to increasing the lifespan of cancer patients. Epithelial-to-mesenchymal transition (EMT) plays a significant role in oncogenic processes, including tumor invasion, intravasation, and micrometastasis formation, and is especially critical for cancer invasion and metastasis. The extracellular matrix (ECM) plays a crucial role in the occurrence of EMT corresponding to the change in adhesion between cells and matrices. CONCLUSION: SPOCK1 is a critical regulator of the ECM and mediates EMT in cancer cells. This suggests an important role for SPOCK1 in tumorigenesis, migration and invasion. SPOCK1 is a critical regulator of some processes involved in cancer progression, including cancer cell proliferation, apoptosis and migration. Herein, the functions of SPOCK1 in cancer progression are expounded, revealing the association between SPOCK1 and EMT in cancer metastasis. SPOCK1 is a positive downstream regulator of transforming growth factor-ß, and SPOCK1-mediated EMT regulates invasion and metastasis through the Wnt/ß-catenin pathway and PI3K/Akt signaling pathway. It is of significance that SPOCK1 may be an attractive prognostic biomarker and therapeutic target in cancer treatment.

14.
Food Res Int ; 130: 108885, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32156346

RESUMO

Limited oxygenation and over-oxidation experiments were designed to compare the phenolic and chromatic characters of base wines Cabernet Franc (CF), Cabernet Sauvignon (CS), and their counterparts that blended with modifier wines Marselan (MA) and Petit Verdot (PV). In both limited oxygenation and over-oxidation conditions, all blend wines generally contained higher C*ab, a* and Red%, and lower hab, b* and Yellow% than their base wine counterparts, because MA contributed flavonols (copigments) and anthocyanins, and PV contributed flavanols (anthocyanin derived pigments precursors). Chromatic changes that can be perceived by human eye (ΔE*ab) in CF based blend wines were more obvious than that of CS based blend wines, which indicate that base wine with lower phenolic concentrations and weak phenolic profiles (CF) might be more prone to be chromatically modified than base wine with higher phenolic concentrations and distinct phenolic profiles (CS). Chemical influences of different blending strategies on anthocyanin derivatives' formations were depending on phenolic profiles of the modifier wines and base wines, and also on the oxygen exposure. The results suggest that the chromatic improvement of base wines could be realized by blending modifier wines under different oxygen exposures.


Assuntos
Qualidade dos Alimentos , Oxigênio/metabolismo , Pigmentos Biológicos/metabolismo , Polifenóis/metabolismo , Vinho , Cor
15.
Neurosci Lett ; 727: 134922, 2020 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-32205185

RESUMO

Our previous experiments found that a suitable dose of vitamin A (VA) can affect neuronal apoptosis after hypoxic-ischemic brain damage (HIBD) by binding to RARα to activate the PI3K/AKT signaling pathway; however, the other neuroprotective effects of VA after HIBD, for example, whether it promotes neural stem cell (NSC) proliferation, remain unclear. In this study, in vivo and in vitro experiments revealed that VA regulates ß-catenin signaling through RARɑ to affect NSC proliferation after HIBD and to improve neurocognitive outcomes. Because of the accumulation and suspended growth characteristics of NSCs, we performed in vitro experiments with PC12 cells to mimic NSCs. Flow cytometry, CCK8, EdU staining, immunofluorescence and behavioral tests were performed to explore the effects of retinoic acid (RA) on NSC proliferation and post-HIBD function. The expression of RARα and ß-catenin pathway components were measured by real-time PCR and Western blotting. We found that the learning and memory of the VA-deficient (VAD) group was more seriously damaged than that of the VA normal (VAN) group. The proliferation of hippocampal NSCs was significantly decreased in the VAD group compared with the VAN group. The mRNA and protein expression of RARɑ, AKT, GSK-3ß, ß-catenin and Cyclin D1 were significantly lower in the VAD group than in the VAN group. In vitro, too high and too low of an RA intervention resulted in decreased proliferation, while an appropriate RA concentration (1-5 µmol/L) significantly promoted proliferation, S phase cells and high ß-catenin pathway expression. These results suggested that VA can exert a neuroprotective effect by promoting the proliferation of hippocampal NSCs after neonatal HIBD injury at the appropriate concentration. VA activates RARɑ, which regulates the ß-catenin signaling pathway, which in turn upregulates Cyclin D1 expression, promotes NSC proliferation, and finally plays a role in the neuroprotective effect.


Assuntos
Proliferação de Células/fisiologia , Hipóxia-Isquemia Encefálica/metabolismo , Células-Tronco Neurais/metabolismo , Transdução de Sinais/fisiologia , Vitamina A/farmacologia , beta Catenina/metabolismo , Animais , Animais Recém-Nascidos , Proliferação de Células/efeitos dos fármacos , Feminino , Hipóxia-Isquemia Encefálica/prevenção & controle , Células-Tronco Neurais/efeitos dos fármacos , Células PC12 , Ratos , Ratos Sprague-Dawley , Receptor alfa de Ácido Retinoico , Transdução de Sinais/efeitos dos fármacos , Vitamina A/uso terapêutico
16.
Carbohydr Polym ; 234: 115891, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32070511

RESUMO

An efficient and bio-based alginate pillared hydrotalcite (SA@LDHs) was fabricated via calcination-reconstruction manner with sodium alginate (SA) and hydrotalcite (LDHs-C), and used as novel flame retardant for polypropylene (PP). The morphologies and combustion properties of SA@LDHs and its hybrid with PP composites (PP/SA@LDHs) had been characterized by SEM, TGA, cone calorimetry, LOI and UL-94 measurements. With 30 wt% loading, the SA@LDHs achieved a LOI value of 30.9 % and a UL-94 V-0 rating, whereas the LDHs-C exhibited only LOI value of 27.6 % and a UL-94 V-1 rating. The peak heat release rate, total heat release and total smoke production of PP/SA@LDHs were 260.8 kW m-2, 61.3 MJ m-2 and 8.2 m2, respectively, which presented declines of 69.2 %, 42.8 % and 32.2 % compared with those of Neat PP. These improvements could be attributed to the presence of the radical-trapping effect of SA, which leading to promote PP chains to participate in the carbonization process.

17.
Zhongguo Zhong Yao Za Zhi ; 43(22): 4370-4379, 2018 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-30593227

RESUMO

Macrophages are a group of immune cells with pluripotency and plasticity that can differentiate into different phenotypes under different microenvironments in vitro and in vivo. In the development of pulmonary fibrosis, there are alveolar macrophages and interstitial macrophages, which are polarized to different cell phenotypes at different stages of development. And their polarized phenotypes include M1 macrophages and M2 macrophages. In the inflammation early stages of pulmonary fibrosis, the increase of classical activated macrophages are helpful to clear pathogenic microorganisms and promote the progress of inflammation. In the fibrosis stage, the alternatively activated macrophages increased, which inhibiting the inflammatory reaction or directly promoting tissue fibrosis, on the other hand, it also promoting the fibrosis degradation. To clarify the polarization and polarization mechanisms of macrophages in pulmonary fibrosis will be conducive to the treatment of pulmonary fibrosis. In IPF, the polarization mechanism of M1 and M2 is closely related to TGF-ß1/Smad. TGF-ß1/Smad pathway plays an important regulatory role in liver fibrosis, renal fibrosis, myocardial fibrosis, scars, tumors and other diseases. Blocking the signaling of TGF-ß1 by Smad3 and Smad4 is beneficial to inhibit the polarization of AM, which in turn helps to inhibit the progression of IPF.


Assuntos
Macrófagos , Fibrose Pulmonar , Fibrose , Humanos , Inflamação , Transdução de Sinais
18.
Genome ; 59(7): 501-7, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27299732

RESUMO

ADP-glucose pyrophosphorylase (AGP), which consists of two large subunits (AGP-L) and two small subunits (AGP-S), controls the rate-limiting step in the starch biosynthetic pathway. In this study, a full-length open reading frame (ORF) of AGP-L gene (named as Agp2) in wheat and a series of Agp2 gene sequences in wheat relatives were isolated. The coding region of Agp2 contained 15 exons and 14 introns including a full-length ORF of 1566 nucleotides, and the deduced protein contained 522 amino acids (57.8 kDa). Generally, the phylogenetic tree of Agp2 indicated that sequences from A- and D-genome donor species were most similar to each other and sequences from B-genome donor species contained more variation. Starch accumulation and Agp2 expression in wheat grains reached their peak at 21 and 15 days post anthesis (DPA), respectively.


Assuntos
Glucose-1-Fosfato Adenililtransferase/genética , Triticum/enzimologia , Triticum/genética , Sequência de Aminoácidos , Sequência de Bases , DNA Complementar/química , DNA Complementar/genética , DNA de Plantas/genética , Regulação da Expressão Gênica de Plantas , Glucose-1-Fosfato Adenililtransferase/biossíntese , Fases de Leitura Aberta , Filogenia , Proteínas de Plantas/química , Proteínas de Plantas/classificação , Proteínas de Plantas/genética , Reação em Cadeia da Polimerase em Tempo Real , Sementes/genética , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Amido/biossíntese
19.
Molecules ; 20(11): 19865-77, 2015 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-26556321

RESUMO

Phenolic compounds determine the color quality of fruit wines. In this study, the phenolic compound content and composition, color characteristics and changes during 6 months of bottle aging were studied in wines fermented with bog bilberry syrup under three different pHs. The total anthocyanins and total phenols were around 15.12-16.23 mg/L and 475.82 to 486.50 mg GAE/L in fresh wines and declined 22%-31% and about 11% in bottle aged wines, respectively. In fresh wines, eight anthocyanins, six phenolic aids and 14 flavonols, but no flavon-3-ols were identified; Malvidin-3-O-glucoside, petunidin-3-O-glucoside and delphinium-3-O-glucoside were the predominant pigments; Chlorogentic acid was the most abundant phenolic acid, and quercetin-3-O-galactoside and myricetin-3-O-galactoside accounted for nearly 90% of the total flavonols. During 6 months of bottle storage, the amounts of all the monomeric anthocyanins and phenolic acids were reduced dramatically, while the glycosidyl flavonols remained constant or were less reduced and their corresponding aglycones increased a lot. The effects of aging on blueberry wine color were described as the loss of color intensity with a dramatic change in color hue, from initial red-purple up to final red-brick nuances, while the pH of the fermentation matrix was negatively related to the color stability of aged wine.


Assuntos
Polifenóis/química , Vaccinium myrtillus/química , Vinho/análise , Antocianinas/química , Fermentação , Flavonóis/química , Concentração de Íons de Hidrogênio , Hidroxibenzoatos/química , Fenóis/química , Pigmentos Biológicos/análise
20.
J Food Sci ; 80(4): C703-10, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25807971

RESUMO

To solve the problem of wine color instability in western China, different additives (the maceration enzymes Vinozym G and Ex-color, yeasts VR5 and Red Star, and commercial tannins) were added during alcoholic fermentation of Syrah (Vitis vinifera L.). The phenolic profile and color characteristics of wine were examined using high performance liquid chromatography mass spectrometry and CIELAB, respectively. The results showed that the combination of the enzyme Ex-color with the Red Star yeast eased the release of non-anthocyanins from grape berries into wine, whereas the use of enzyme Vinozym G and VR5 yeast enhanced the concentration of anthocyanins and achieved a higher red hue (a* value) and a lower yellow hue (b* value) in the wine. The addition of commercial tannins greatly promoted the level of gallic acid in the wine and led to a relatively higher concentration of anthocyanins. Partial least-squares regression analysis was used to find out the major phenolics, which were in close relation with color parameters; principal component analysis was used to evaluate the contribution of different winemaking techniques to wine color. The combination of these 2 analytic methods indicated that Vinozym G and VR5 yeast together with commercial tannins should be an appropriate combination to enhance the stability of wine color during alcohol fermentation, which was related to a significant increase in cyanidin-3-O-(6-O-acetyl)-glucoside, cyanidin-3-O-(6-O-coumaryl)-glucoside, trans-peonidin-3-O-(6-O-coumaryl)-glucoside, trans-malvidin-3-O-(6-O-coumaryl)-glucoside, and malvidin-3-O-(6-O-acetyl)-glucoside-pyruvic acid, all of which played an important role in stabilizing wine color.


Assuntos
Cor , Fermentação , Frutas/metabolismo , Polifenóis/metabolismo , Vitis , Vinho/análise , Álcoois/metabolismo , Antocianinas/metabolismo , China , Glucosídeos/metabolismo , Humanos , Análise dos Mínimos Quadrados , Fenóis/metabolismo , Análise de Componente Principal , Taninos/metabolismo
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