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Effective crosslinking among food constituents has the potential to enhance their overall quality. Distarch phosphate (DSP), a common food additive employed as a thickening agent, bears a pre-crosslinked oligosaccharide (PCO) moiety within its molecular structure. Once this moiety is released, its double reducing end has the potential to undergo crosslinking with amino-rich macromolecules through Maillard reaction. In this study, hydrolyzed distarch phosphate (HDSP) was synthesized, and spectroscopic analysis verified the presence of PCO within HDSP. Preliminary validation experiment showed that HDSP could crosslink chitosan to form a hydrogel and significant browning was also observed during the process. Furthermore, rehydrated sea cucumber (RSC) crosslinked with HDSP exhibited a more intact appearance, higher mechanical strength, better color profile, and increased water-holding capacity. This series of results have confirmed that HDSP is capable to crosslink amino-rich macromolecules and form more stable three-dimensional network.
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Fosfatos , Pepinos-do-Mar , Animais , Pepinos-do-Mar/química , Hidrólise , Fosfatos/química , Aditivos Alimentares/química , Reagentes de Ligações Cruzadas/química , Reação de Maillard , Oligossacarídeos/químicaRESUMO
Sugar is a primary determinant of citrus fruit flavour, but undergoes varied accumulation processes across different citrus varieties owing to high genetic variability. Sucrose phosphate synthase (SPS), a key enzyme in glucose metabolism, plays a crucial role in this context. Despite its significance, there is limited research on sugar component quality and the expression and regulatory prediction of SPS genes during citrus fruit development. Therefore, we analysed the sugar quality formation process in 'Kiyomi' and 'Succosa', two citrus varieties, and performed a comprehensive genome-wide analysis of citrus CsSPSs. We observed that the accumulation of sugar components significantly differs between the two varieties, with the identification of four CsSPSs in citrus. CsSPS sequences were highly conserved, featuring typical SPS protein domains. Expression analysis revealed a positive correlation between CsSPS expression and sugar accumulation in citrus fruits. However, CsSPS expression displays specificity to different citrus tissues and varieties. Transcriptome co-expression network analysis suggests the involvement of multiple transcription factors in shaping citrus fruit sugar quality through the regulation of CsSPSs. Notably, the expression levels of four CsWRKYs (CsWRKY2, CsWRKY20, CsWRKY28, CsWRKY32), were significantly positively correlated with CsSPSs and CsWRKY20 might can activate sugar accumulation in citrus fruit through CsSPS2. Collectively, we further emphasize the potential importance of CsWRKYs in citrus sugar metabolism, our findings serve as a reference for understanding sugar component formation and predicting CsSPS expression and regulation during citrus fruit development.
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Breast cancer (BC) is the most common malignancy among women and a leading cause of cancer-related deaths of females worldwide. It is a complex and molecularly heterogeneous disease, with various subtypes that require different treatment strategies. Despite advances in high-resolution single-cell and multinomial technologies, distant metastasis and therapeutic resistance remain major challenges for BC treatment. Long non-coding RNAs (lncRNAs) are non-coding RNAs with more than 200 nucleotides in length. They act as competing endogenous RNAs (ceRNAs) to regulate post-transcriptional gene stability and modulate protein-protein, protein-DNA, and protein-RNA interactions to regulate various biological processes. Emerging evidence suggests that lncRNAs play essential roles in human cancers, including BC. In this review, we focus on the roles and mechanisms of lncRNAs in BC progression, metastasis, and treatment resistance, and discuss their potential value as therapeutic targets. Specifically, we summarize how lncRNAs are involved in the initiation and progression of BC, as well as their roles in metastasis and the development of therapeutic resistance. We also recapitulate the potential of lncRNAs as diagnostic biomarkers and discuss their potential use in personalized medicine. Finally, we provide lncRNA-based strategies to promote the prognosis of breast cancer patients in clinical settings, including the development of novel lncRNA-targeted therapies.
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BACKGROUND: Selenium is an important nutritional supplement that mainly exists naturally in soil as inorganic selenium. Saccharomyces cerevisiae cells are excellent medium for converting inorganic selenium in nature into organic selenium. RESULTS: Under the co-stimulation of sodium selenite (Na2SeO3) and potassium selenite (K2SeO3), the activity of selenophosphate synthetase (SPS) was improved up to about five folds more than conventional Na2SeO3 group with the total selenite salts content of 30 mg/L. Transcriptome analysis first revealed that due to the sharing pathway between sodium ion (Na+) and potassium ion (K+), the K+ largely regulates the metabolisms of amino acid and glutathione under the accumulation of selenite salt. Furthermore, K+ could improve the tolerance performance and selenium-biotransformation yields of Saccharomyces cerevisiae cells under Na2SeO3 salt stimulation. CONCLUSION: The important role of K+ in regulating the intracellular selenium accumulation especially in terms of amino acid metabolism and glutathione, suggested a new direction for the development of selenium-enrichment supplements with Saccharomyces cerevisiae cell factory. © 2024 Society of Chemical Industry.
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Saccharomyces , Selênio , Selênio/metabolismo , Saccharomyces/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Selenito de Sódio/metabolismo , Ácido Selenioso/metabolismo , Glutationa/metabolismo , Sódio/metabolismo , Aminoácidos/metabolismo , Potássio/metabolismoRESUMO
Introduction: The oil palm kernel (OPK) expeller is the main byproduct of palm oil, but its utilization is limited. Methods: To obtain angiotensin-I-converting enzyme (ACE) inhibition peptides with Zn-chelating capacity, defatted oil palm kernel globulin hydrolysates (DOPKGH) were subjected to Sephadex G-15 gel electrophoresis, reverse-phase high liquid performance chromatography, and UPLC-ESI-MS/MS analysis. Results and discussion: Five representative oligopeptides, including Gln-Arg-Leu-Asp-Arg-Cys-Lys (QRLERCK), Leu-Leu-Leu-Gly-Val-Ala-Asn-Tyr-Arg (LLLGVANYR), Arg-Ala-Asp-Val-Phe-Asn-Pro-Arg (RADVFNPR), Arg-Val-Ile-Lys-Tyr-Asn-Gly-Gly-Gly-Ser-Gly (RVIKYNGGGSG), and Glu-Val-Pro-Gln-Ala-Tyr-Ile-Pro (EVPQAYIP), without potential toxicity and allergenicity, were identified in DOPKGH. Of these, only EVPQAYIP showed both ACE-inhibitory activity (IC50: 102.75 µmol/L) and Zn-chelating capacity (11.69 mg/g). Molecular docking and inhibition kinetics showed that EVPQAYIP was a competitive inhibitor of ACE because it could bind to Glu384, Lys511, and Gln281 (belonging to the central S1 and S2 pockets, respectively) of ACE. Moreover, EVPQAYIP affects zinc tetrahedral coordination in ACE by binding to Glu411; the amino and carboxyl groups of EVPQAYIP chelate with zinc ions. During gastrointestinal digestion, the ACE inhibitory activity of EVPQAYIP was relatively stable. Additionally, EVPQAYIP enhanced zinc stability in the intestine and exerted antihypertensive effects in spontaneous hypertensive rats. These results suggest the potential application of OPK peptides as ingredients in antihypertensive agents or zinc fortification.
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In this study, naked oat bran albumin hydrolysates (NOBAH) were subjected to gel chromatography with Sephadex G-15, reverse phase-high liquid performance separation, and UPLC-ESI-MS/MS identification. Six safe peptides including Gly-Thr-Thr-Gly-Gly-Met-Gly-Thr (GTTGGMGT), Gln-Tyr-Val-Pro-Phe (QYVPF), Gly-Ala-Ala-Ala-Ala-Leu-Val (GAAAALV), Gly-Tyr-His-Gly-His (GYHGH), Gly-Leu-Arg-Ala-Ala-Ala-Ala-Ala-Ala-Glu-Gly-Gly (GLRAAAAAAEGG), and Pro-Ser-Ser-Pro-Pro-Ser (PSSPPS) were identified. Next, in silico screening demonstrated that QYVPF and GYHGH had both angiotensin-I-converting enzyme (ACE) inhibition activity (IC50: 243.36 and 321.94 µmol/L, respectively) and Zinc-chelating ability (14.85 and 0.32 mg/g, respectively). The inhibition kinetics demonstrated that QYVPF and GYHGH were both uncompetitive inhibitors of ACE. Molecular docking showed that QYVPF and GYHGH could bind, respectively, three and five active residues of ACE with short hydrogen bonds (but not belonging to any central pocket). QYVPF and GYHGH could bind, respectively, twenty-two and eleven residues through hydrophobic interactions. Moreover, GYHGH was able to affect zinc tetrahedral coordination in ACE by interacting with His383. The inhibition activities of QYVPF and GYHGH toward ACE were relatively resistant to gastrointestinal digestion. GYHGH improved zinc solubility in the intestines (p > 0.05) because its amino and carboxyl groups were chelating sites for zinc ions. These results suggest the potential applications of naked oat peptides for potential antihypertension or zinc fortification.
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Vascular aging is an important factor contributing to cardiovascular diseases, such as hypertension and atherosclerosis. Hyperlipidemia or fatty accumulation may play an important role in vascular aging and cardiovascular diseases. Canagliflozin (CAN), a sodium-glucose cotransporter inhibitor, can exert a cardiovascular protection effect that is likely independent of its hypoglycemic activities; however, the exact mechanisms remain undetermined. We hypothesized that CAN might have protective effects on blood vessels by regulating vascular aging induced by hyperlipidemia or fatty accumulation in blood vessel walls. In this study, which was undertaken on the basis of aging and inflammation, we investigated the protective effects and mechanisms of CAN in human umbilical vein endothelial cells induced by palmitic acid. We found that CAN could delay vascular aging, reduce the secretion of the senescence-associated secretory phenotype (SASP) and protect DNA from damage, as well as exerting an effect on the cell cycle of senescent cells. These actions likely occur through the attenuation of the excess reactive oxygen species (ROS) produced in vascular endothelial cells and/or down-regulation of the p38/JNK signaling pathway. In summary, our study revealed a new role for CAN as one of the sodium-dependent glucose transporter 2 inhibitors in delaying lipotoxicity-induced vascular aging by targeting the ROS/p38/JNK pathway, giving new medicinal value to CAN and providing novel therapeutic ideas for delaying vascular aging in patients with dyslipidemia.
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R2R3 MYBs play vital roles in the regulation of flavonoid biosynthesis. However, the regulatory network of R2R3 MYBs in flavonoid biosynthesis is not fully understood in grape hyacinth (Muscari spp.). Here, we identified two R2R3 MYBs, MaMYBF and MaMYB1, as potential regulators of flavonol and anthocyanin biosynthesis, respectively. MaMYBF and MaMYB1 expression was elevated during flower development and was light-induced, and the expression patterns were related to those of the flavonoid structural genes MaFLS and MaDFR, respectively. The BiFC assay verified that MaMYB1 interacts with MabHLH1, but MaMYBF does not. A dual luciferase assay revealed that MaMYBF alone strongly activated pMaFLS, and its activation was attenuated at reduced doses of MaMYBF in the presence of MabHLH1, MaMybA, and MaMYB1. MaDFR transcription mediated by MaMybA and MabHLH1 was inhibited by MaMYB1. Moreover, overexpression of MaMYBF and MaMYB1 in tobacco reduced flower pigmentation and repressed the expression of flavonoid pathway key structural genes. Therefore, MaMYBF regulates the flavonol pathway independently of cofactors. Whereas MaMYB1 regulates anthocyanin biosynthesis by binding to MabHLH1 and disrupting the MaMybA-bHLH complex in grape hyacinth. Our results offer new insights into the intricate regulatory network of flavonoids in grape hyacinth involving the regulation of both flavonol and anthocyanin.
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Asparagaceae , Hyacinthus , Vitis , Fatores de Transcrição/metabolismo , Antocianinas/metabolismo , Hyacinthus/metabolismo , Vitis/genética , Vitis/metabolismo , Proteínas de Plantas/metabolismo , Flavonoides , Flavonóis , Asparagaceae/metabolismo , Regulação da Expressão Gênica de PlantasRESUMO
Floral colour is an important agronomic trait that influences the commercial value of ornamental plants. Anthocyanins are a class of flavonoids and confer diverse colours, and elucidating the molecular mechanisms that regulate their pigmentation could facilitate artificial manipulation of flower colour in ornamental plants. Here, we investigated the regulatory mechanism of light-induced anthocyanin biosynthesis during flower colouration in grape hyacinth (Muscari spp.). We studied the function of two B-box proteins, MaBBX20 and MaBBX51. The qPCR revealed that MaBBX20 and MaBBX51 were associated with light-induced anthocyanin biosynthesis. Both MaBBX20 and MaBBX51 are transcript factors and are specifically localised in the nucleus. Besides, overexpression of MaBBX20 in tobacco slightly increased the anthocyanin content of the petals, but reduced in MaBBX51 overexpression lines. The yeast one-hybrid assays indicated that MaBBX20 and MaBBX51 did not directly bind to the MaMybA or MaDFR promoters, but MaHY5 did. The BiFC assay revealed that MaBBX20 and MaBBX51 physically interact with MaHY5. A dual luciferase assay further confirmed that the MaBBX20-MaHY5 complex can strongly activate the MaMybA and MaDFR transcription in tobacco. Moreover, MaBBX51 hampered MaBBX20-MaHY5 complex formation and repressed MaMybA and MaDFR transcription by physically interacting with MaHY5 and MaBBX20. Overall, the results suggest that MaBBX20 positively regulates light-induced anthocyanin biosynthesis in grape hyacinth, whereas MaBBX51 is a negative regulator.
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Asparagaceae , Hyacinthus , Vitis , Antocianinas/metabolismo , Asparagaceae/metabolismo , Regulação da Expressão Gênica de Plantas , Hyacinthus/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Nicotiana/genética , Nicotiana/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Vitis/genética , Vitis/metabolismoRESUMO
Berberine is an isoquinoline alkaloid isolated from Chinese herbal medicines such as Coptis chinensis. It has many pharmacological actions, such as antibacterial, hypoglycemic, anti-inflammatory, and so on. However, due to the low lipophilicity of berberine, it is difficult to penetrate the bacterial cell membrane and also difficult to be absorbed orally and usually needs a relatively high dose to achieve the ideal effect. The purpose of this study is to transform the structure of berberine in order to improve the bioavailability of berberine and reduce the dosage. Moreover, we introduce a pharmacophore named Canagliflozin, a hypoglycemic drug (which was also found to have potential anti-bacterial activity) into BBR to see whether this new compound has more existed activities. We at first connected berberine with Canagliflozin, to form a new compound (BC) and see whether BC has synergic effects. We use microbroth dilution method to determine the minimum inhibitory concentration of BC, determine the bacterial growth with the enzyme labeling instrument, observe the formation of bacterial biofilm with crystal violet staining method, observe the bacterial morphology with field emission scanning electron microscope, and determine the intracellular protein with SDS-PAGE. The above indicators reflect the damage of BC to bacteria. New compound BC was successfully obtained by chemical synthesis. The minimal inhibitory concentration of compound BC on three bacteria was significantly better than that of berberine and canagliflozin alone and the combination of berberine and canagliflozin. Moreover, compound BC has obvious destructive effect on bacterial morphology and biofilm, and the compound also has destructive effect on intracellular proteins. Therefore, new compound BC has broad-spectrum antibacterial activity and the inhibitory effect of BC might play a role by destroying the integrity of biofilm and the intracellular protein of bacteria. In conclusion, we create a new molecular entity of berberine and Canagliflozin chimera and open up a new prospect for berberine derivatives in the treatment of bacterial infection.
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Berberina , Antibacterianos/farmacologia , Canagliflozina/farmacologia , Hipoglicemiantes/farmacologia , Testes de Sensibilidade MicrobianaRESUMO
NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome is an important component of the innate immune system that mediates the secretion of the pro-inflammatory cytokines interleukin-1ß (IL-1ß) and IL-18. However, current studies have shown that the abnormal activation of the NLRP3 inflammasome is associated with inflammatory diseases such as atherosclerosis, diabetes, and pneumonia. In this study, we found that canagliflozin (CAN) transcriptionally inhibited NLRP3 inflammasome-related proteins by inhibiting the transduction of the nuclear factor κB signal. Autophagy is largely involved in the post-translational modifications of the NLRP3 inflammasome and is an important regulator of NLRP3 inflammasome assembly and activation. Bax-interacting factor 1 (Bif-1) plays an important role in autophagosome formation during early-stage autophagy. Our results are the first to indicate that CAN, a hypoglycemic drug, can inhibit the activation of NLRP3 inflammasome and inflammation by upregulating Bif-1 and autophagy in a non-hypoglycemic manner. This study provides new information regarding the treatment of patients with pneumonia, particularly those with concurrent diabetes.
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Colitis is not fully curable, although currently, some treatment options are being adopted. In this study, we investigated the effects of pineapple leaf phenols (PLPs), natural phenol products from pineapple leaves, on DSS-induced colitis in mice. The results showed that PLPs dramatically decreased the inflammatory response by inhibiting NF-κB activation and the secretion of pro-inflammatory factors. Moreover, PLPs provided protection against DSS-induced acute colitis by maintaining epithelial integrity. Caffeic and P-coumaric acids had similar effects and could be the active components responsible for PLPs' effect on colitis. These results indicate that the oral administration of PLPs might be considered as a therapeutic strategy in the treatment of patients with colitis. However, further research on clinical applications and the exact effect of PLPs on colitis is required.
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Ananas/química , Ácidos Cafeicos , Colite , Ácidos Cumáricos , Sulfato de Dextrana/toxicidade , NF-kappa B/metabolismo , Folhas de Planta/química , Transdução de Sinais/efeitos dos fármacos , Animais , Ácidos Cafeicos/química , Ácidos Cafeicos/farmacologia , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/metabolismo , Ácidos Cumáricos/química , Ácidos Cumáricos/farmacologia , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Masculino , Camundongos , Fenóis/química , Fenóis/farmacologiaRESUMO
In this paper, we give a rather complete analysis for a susceptible-infective sexually transmitted disease (STD) model, where the males are divided into two different groups based on their different sexual orientation. The threshold [Formula: see text] of STD model is obtained. If [Formula: see text], the disease-free equilibrium is globally asymptotically stable. Further, we investigate the existence and stability of the boundary equilibria that characterize the males of the different sexual orientation. We also investigate the existence and stability of the positive equilibrium, which characterizes the possibility of coexistence of male heterosexual and male homosexual. We obtain sufficient and necessary conditions for the existence and global stability of these equilibria. We see that the proportion of heterosexuality in MSM affects the stability of the system. The theoretical results are verified by numerical simulation.
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Minorias Sexuais e de Gênero , Infecções Sexualmente Transmissíveis , Feminino , Heterossexualidade , Homossexualidade Masculina , Humanos , Masculino , Comportamento Sexual , Infecções Sexualmente Transmissíveis/epidemiologiaRESUMO
Background: BRCA1 plays critical roles in mammary gland development and mammary tumorigenesis. And loss of BRCA1 induces mammary tumors in a stochastic manner. These tumors present great heterogeneity at both intertumor and intratumor levels. Methods: To comprehensively elucidate the heterogeneity of BRCA1 deficient mammary tumors and the underlying mechanisms for tumor initiation and progression, we conducted bulk and single cell RNA sequencing (scRNA-seq) on both mammary gland cells and mammary tumor cells isolated from Brca1 knockout mice. Results: We found the BRCA1 deficient tumors could be classified into four subtypes with distinct molecular features and different sensitivities to anti-cancer drugs at the intertumor level. Whereas within the tumors, heterogeneous subgroups were classified mainly due to the different activities of cell proliferation, DNA damage response/repair and epithelial-to-mesenchymal transition (EMT). Besides, we reconstructed the BRCA1 related mammary tumorigenesis to uncover the transcriptomes alterations during this process via pseudo-temporal analysis of the scRNA-seq data. Furthermore, from candidate markers for BRCA1 mutant tumors, we discovered and validated one oncogene Mrc2, whose loss could reduce mammary tumor growth in vitro and in vivo. Conclusion: Our study provides a useful resource for better understanding of mammary tumorigenesis induced by BRCA1 deficiency.
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Proteína BRCA1/genética , Neoplasias da Mama/genética , Carcinogênese/genética , Animais , Proteína BRCA1/metabolismo , Mama/patologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Transformação Celular Neoplásica/genética , Reparo do DNA/genética , Transição Epitelial-Mesenquimal/genética , Feminino , Expressão Gênica/genética , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica/genética , Genes BRCA1/fisiologia , Heterogeneidade Genética , Humanos , Neoplasias Mamárias Animais/genética , Neoplasias Mamárias Animais/patologia , Camundongos , Camundongos da Linhagem 129 , Camundongos Endogâmicos C57BL , Camundongos Knockout , Análise de Sequência de RNA/métodos , Análise de Célula Única/métodos , Transcriptoma/genéticaRESUMO
Nasopharyngeal carcinoma (NPC) is a malignant head and neck cancer type with high morbidity in Southeast Asia, however the pathogenic mechanism of this disease is poorly understood. Using integrative pharmacogenomics, we find that NPC subtypes maintain distinct molecular features, drug responsiveness, and graded radiation sensitivity. The epithelial carcinoma (EC) subtype is characterized by activations of microtubule polymerization and defective mitotic spindle checkpoint related genes, whereas sarcomatoid carcinoma (SC) and mixed sarcomatoid-epithelial carcinoma (MSEC) subtypes exhibit enriched epithelial-mesenchymal transition (EMT) and invasion promoting genes, which are well correlated with their morphological features. Furthermore, patient-derived organoid (PDO)-based drug test identifies potential subtype-specific treatment regimens, in that SC and MSEC subtypes are sensitive to microtubule inhibitors, whereas EC subtype is more responsive to EGFR inhibitors, which is synergistically enhanced by combining with radiotherapy. Through combinational chemoradiotherapy (CRT) screening, effective CRT regimens are also suggested for patients showing less sensitivity to radiation. Altogether, our study provides an example of applying integrative pharmacogenomics to establish a personalized precision oncology for NPC subtype-guided therapies.
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Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/genética , Farmacogenética/métodos , Avaliação Pré-Clínica de Medicamentos/métodos , Transição Epitelial-Mesenquimal , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Técnicas de Inativação de Genes , Humanos , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/patologia , Medicina de Precisão , Transcriptoma , Sequenciamento do ExomaRESUMO
Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and devastating cancers without effective treatments. Amplified in breast cancer 1 (AIB1) is a member of the steroid receptor coactivator family that mediates the transcriptional activities of nuclear receptors. While AIB1 is associated with the initiation and progression of multiple cancers, the mechanism by which AIB1 contributes to PDAC progression remains unknown. In this study, we aimed to explore the role of AIB1 in the progression of PDAC and elucidate the underlying mechanisms. Methods: The clinical significance and mRNA level of AIB1 in PDAC were studied by database analysis. To demonstrate whether AIB1 mediates the malignant features of PDAC cells, namely, proliferation, migration, invasion, we performed real-time PCR and Western blot analysis, established xenograft models and used in vivo metastasis assay. With insights into the mechanism of AIB1, we performed RNA sequencing (Seq), ChIP-Seq, luciferase reporter assays and pull-down assays. Furthermore, we analyzed the relationship between AIB1 expression and its target expression in PDAC cells and patients and explored whether PDAC cells with high AIB1 levels are sensitive to inhibitors of its target. Results: We found that AIB1 was significantly upregulated in PDAC and associated with its malignancy. Silencing AIB1 impaired hedgehog (Hh) activation by reducing the expression of smoothened (SMO), leading to cell cycle arrest and the inhibition of PDAC cell proliferation. In addition, AIB1, via upregulation of integrin αv (ITGAV) expression, promoted extracellular matrix (ECM) signaling, which played an important role in PDAC progression. Further studies showed that AIB1 preferably bound to AP-1 related elements and served as a coactivator for enhancing the transcriptional activity of MafB, which promoted the expression of SMO and ITGAV. PDAC cells with high AIB1 levels were sensitive to Hh signaling inhibitors, suggesting that blocking Hh activation is an effective treatment against PDAC with high AIB1 expression. Conclusions: These findings reveal that AIB1 is a crucial oncogenic regulator associated with PDAC progression via Hh and ECM signaling and suggest potential therapeutic targets for PDAC treatment.
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Biomarcadores Tumorais/metabolismo , Carcinoma Ductal Pancreático/secundário , Regulação Neoplásica da Expressão Gênica , Proteínas Hedgehog/metabolismo , Coativador 3 de Receptor Nuclear/metabolismo , Neoplasias Pancreáticas/patologia , Animais , Apoptose , Biomarcadores Tumorais/genética , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/metabolismo , Movimento Celular , Proliferação de Células , Proteínas Hedgehog/genética , Humanos , Masculino , Camundongos , Camundongos SCID , Coativador 3 de Receptor Nuclear/genética , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Prognóstico , Taxa de Sobrevida , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto , Neoplasias PancreáticasRESUMO
A visualized assay for miRNAs detection has been developed in this work. The presented method is based on a combination of enzyme-free amplification cascades of catalyzed hairpin assembly (CHA) and hybridization chain reaction (HCR) and fluorescence quenching of dual-emission ratiometric fluorescent probes (RF probes). MiRNAs can efficiently initiate enzyme-free amplification reactions (CHA and HCR) and produce the long nicked dsDNAs with a lot of glucose oxidases (GOD) on the surface of dynabeads bridged by the GOD-labeled hairpin DNA probes. Hydrogen peroxide (H2O2) is generated by oxidation of glucose catalyzed by GOD, which can quench the outer green fluorescence without affecting the internal red fluorescence of RF probes. Therefore, increased miRNA amount can result in change of the two fluorescence intensity ratios of RF probes with continuous color changes from green to red under a UV lamp, which can be easily recognized by naked eye. The proposed assay exhibits high sensitivity toward let-7a with dynamic range from 10-13 M to 10-8 M, and which is applied successfully to detecting let-7a in the small RNA samples.
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Técnicas Biossensoriais , MicroRNAs , Corantes Fluorescentes , Peróxido de Hidrogênio , Limite de Detecção , Hibridização de Ácido NucleicoRESUMO
The breast cancer susceptibility gene 1 (BRCA1) is a major tumor suppressor gene and is most frequently mutated in hereditary breast cancer. BRCA1 plays a critical role in many biological processes, especially maintaining genomic stability in the nucleus, yet its role in the cytoplasm remains elusive. Here, it is revealed that BRCA1 maintains a healthy mitochondrial network through regulating mitochondrial dynamics, including fission and fusion. BRCA1 deficiency causes dysfunctional mitochondrial dynamics through increased expression of mitofusin1/2. With mitochondrial stress, BRCA1 is recruited to the mitochondrial outer membrane, where it plays an essential role in maintaining a healthy mitochondrial network. Consequently, BRCA1 deficiency impairs stress-induced mitophagy through blocking ataxia-telangiectasia mutated (ATM)-AMP-activated protein kinase (AMPK)-Dynamin-related protein 1 (DRP1)-mediated mitochondrial fission and triggers NLRP3 inflammasome activation, which creates a tumor-associated microenvironment, thereby facilitating tumor proliferation and metastasis. It is further shown that inflammasome inhibition can prevent tumor recurrence and metastasis. This study uncovers an important role of BRCA1 in regulating mitophagy and suggests a therapeutic approach for fighting this deadly disease.
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With the rapid development of modern biotechnology, fermentation process is increasingly important in industrial production. To guarantee the stability of products, fermentation process should be elaborately monitored and controlled. Biomass is an important parameter for on-line monitoring in bioprocesses because biomass can reflect cell growth in a bioreactor directly. In-situ microscope, a non-invasive and image-analysis based technology, can real-time monitor cells in biological process. This review summarizes the development and application of in-situ microscopy in biomass monitoring.
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Biomassa , Microscopia , Reatores Biológicos , Biotecnologia , FermentaçãoRESUMO
The influences of nano-bacterial cellulose (Nano-BC)/soy protein isolate (SPI) complex gel on the textural, rheological, and sensory properties of the ice cream model were investigated. Nano-BC/SPI mixtures with different ratios (Nano-BC:SPI, 1:20, 1:15, 1:10, and 1:5 w/w) were prepared with constant total solid content (16%). Compared with pure SPI, the thermal stability, textural, rheological and emulsifying properties of nano-BC/SPI mixtures were improved. Microstructure of nano-BC/SPI complex gels showed that low doses of nano-BC (1:20, 1:15, and 1:10) had good compatibility with SPI matrix according to images of confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM). Nano-BC/SPI (1:20) had the most similar textural properties to the cream. When 20% of nano-BC/SPI (1:20) mixture was added into ice cream as the cream substitute, the anticipated ice cream with low calorie, melting resistance, and good textural properties was achieved.