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1.
RSC Adv ; 14(14): 9472-9481, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38516163

RESUMO

Quercetin (QCT) has a variety of pharmacological effects, such as antioxidant, antibacterial, anticancer, anticardiovascular and antiaging effects. However, its poor water solubility, stability and bioavailability limit its applications. The special structure of cyclodextrins and their derivatives with a hydrophobic inner cavity and hydrophilic outer wall can load a variety of hydrophobic drugs of a suitable size and shape, thereby improving the stability and solubility of these molecules. In this study, an inclusion complex of quercetin and sulfobutylether-ß-cyclodextrin was prepared. It was characterized via FT-IR, UV, 1H NMR, XRD, DSC, and SEM analysis, which revealed the successful formation of the inclusion complex. In vitro biological activity estimations were carried out and the results indicated that the inclusion complex displayed higher antioxidative and antibacterial properties compared with free QCT. In addition, the mechanisms of inclusion were explored using 1H NMR analysis and docking calculations, thus providing a theoretical basis for obtaining an inclusion complex.

2.
Front Med (Lausanne) ; 10: 1256176, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38076257

RESUMO

Neuroendocrine tumors (NETs) are a heterogeneous group of tumors originating from peptide-producing neurons and neuroendocrine cells. The liver is the most common site of metastasis for NETs, while primary hepatic neuroendocrine tumors (PHNETs) are exceedingly rare. While somatostatin receptor scintigraphy (SRS) has demonstrated superior efficacy compared to [18F]FDG PET imaging in the diagnosis of neuroendocrine tumors, [18F]AlF-NOTA-Octreotide ([18F]AlF-OC) PET/CT also exhibits specific advantages over SRS. This article presents a case study of a patient with a liver mass who underwent sequential [18F]FDG and [18F]AlF-OC PET/CT scans, ruling out hepatocellular carcinoma and confirming the diagnosis of PHNETs. Subsequently, the patient underwent surgical treatment. From another perspective, [18F]AlF-OC exhibits distinct advantages. The postoperative pathology revealed a PHNETs, which further emphasizes its clinical rarity.

4.
Front Immunol ; 14: 1230261, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37671157

RESUMO

Intrahepatic cholangiocarcinoma (ICC) is one of the most common invasive malignant tumors, with a 5-year survival rate of less than 5%. Currently, radical surgical resection is the preferred treatment for ICC. However, most patients are only diagnosed at an advanced stage and are therefore not eligible for surgery. Herein, we present a case of advanced ICC in which radical surgery was not possible due to tumor invasion of the second porta hepatis and right hepatic artery. Six treatment cycles with a gemcitabine and oxaliplatin (GEMOX) regimen combined with camrelizumab immunotherapy achieved a partial response and successful tumor conversion, as tumor invasion of the second porta hepatis and right hepatic artery was no longer evident. The patient subsequently underwent successful radical surgical resection, including hepatectomy, caudate lobe resection, and cholecystectomy combined with lymph node dissection. Cases of patients with advanced ICC undergoing surgical resection after combined immunotherapy and chemotherapy are rare. The GEMOX regimen combined with camrelizumab demonstrated favorable antitumor efficacy and safety, suggesting that it might be a potential feasible and safe conversion therapy strategy for patients with advanced ICC.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Humanos , Gencitabina , Oxaliplatina , Ductos Biliares Intra-Hepáticos
5.
Artigo em Inglês | MEDLINE | ID: mdl-37658838

RESUMO

Aims: Reactive oxygen species (ROS) play a vital role in conveying the cytotoxicity and resistance of most chemotherapy drugs. Therefore, gaining a comprehensive understanding of the intricate activities against oxidative stress in cancer cells may provide valuable insights into the discovery of common mechanisms underlying chemoresistance. Results: We identified a novel long noncoding RNA (lncRNA), designated fluorouracil-associated transcript-1 (FUAT1), as a key nongenetic player involved in ROS-mediated intrinsic chemoresistance by employing a unique screening strategy based on transcriptome sequencing (RNA-Seq) technology. To investigate the precise role of the FUAT1 regulatory axis in chemoresistance, we conducted a series of in vitro and in vivo assays including gain/loss-of-function and rescue experiments. Mechanistically, our findings revealed that FUAT1 upregulates Tensin 4 (TNS4) by sponging miR-140-5p, which allows gastric cancer cells to survive chemotherapy by inhibiting ROS-mediated apoptosis. Clinically, we observed that the FUAT1/TNS4 regulatory axis is negatively associated with overall survival and progression-free survival among gastric and colon cancer patients treated with 5-fluorouracil adjuvant chemotherapy. Innovation: We devised a novel screening strategy distinct from conventional approaches using drug-resistant strains. Through this approach, we identified the previously unrecognized lncRNA FUAT1/TNS4 axis that plays a critical role in ROS-mediated intrinsic chemoresistance. Conclusions: Our findings shed light on fundamental adaptive mechanisms employed by cancer cells to respond to chemotherapy and provide new insights into developing strategies aiming at overcoming chemoresistance.

6.
J Transl Med ; 21(1): 461, 2023 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-37434177

RESUMO

BACKGROUND: Nearly 80% of patients with pancreatic cancer suffer from glucose intolerance or diabetes. Pancreatic cancer complicated by diabetes has a more immunosuppressive tumor microenvironment (TME) and is associated with a worse prognosis. The relationship between glucose metabolism and programmed cell death-Ligand 1 (PD-L1) is close and complex. It is important to explore the regulation of high glucose on PD-L1 expression in pancreatic cancer and its effect on infiltrating immune effectors in the tumor microenvironment. METHODS: Diabetic murine models (C57BL/6) were used to reveal different immune landscape in euglycemic and hyperglycemic pancreatic tumor microenvironment. Bioinformatics, WB, iRIP [Improved RNA Binding Protein (RBP) Immunoprecipitation]-seq were used to confirm the potential regulating role of peptidyl-tRNA hydrolase 1 homolog (PTRH1) on the stability of the PD-L1 mRNA. Postoperative specimens were used to identify the expression of PD-L1 and PTRH1 in pancreatic cancer. Co-culturing T cells with pancreatic cancer cells to explore the immunosuppressive effect of pancreatic tumor cells. RESULTS: Our results revealed that a high dose of glucose enhanced the stability of the PD-L1 mRNA in pancreatic tumor cells by downregulating PTRH1 through RAS signaling pathway activation following epidermal growth factor receptor (EGFR) stimulation. PTRH1 overexpression significantly suppressed PD-L1 expression in pancreatic cells and improved the proportion and cytotoxic function of CD8+ T cells in the pancreatic TME of diabetic mice. CONCLUSIONS: PTRH1, an RBP, plays a key role in the regulation of PD-L1 by high glucose and is closely related to anti-tumor immunity in the pancreatic TME.


Assuntos
Antineoplásicos , Antígeno B7-H1 , Diabetes Mellitus Experimental , Neoplasias Pancreáticas , Animais , Camundongos , Antígeno B7-H1/genética , Linfócitos T CD8-Positivos , Regulação para Baixo/genética , Camundongos Endogâmicos C57BL , Neoplasias Pancreáticas/genética , Transdução de Sinais , Microambiente Tumoral , Neoplasias Pancreáticas
7.
Foods ; 12(13)2023 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-37444202

RESUMO

Baijiu, a prevalent alcoholic beverage, boasts over 2000 aroma compounds, with sulfur-containing compounds being the most influential in shaping its flavor. Benzenemethanethiol, a distinctive odorant in baijiu, is known to enhance the holistic flavor profile of baijiu. Despite its importance, there is very little literature on the biotransformation mechanism of benzenemethanethiol. Thus, extensive research efforts have been made to elucidate the formation mechanism of this compound in order to improve baijiu production. In this study, 12 yeast strains capable of generating benzenemethanethiol were isolated from baijiu daqu, and the Saccharomyces cerevisiae strain J14 was selected for further investigation. The fermentation conditions were optimized, and it was found that the optimal conditions for producing benzenemethanethiol were at 28 °C for 24 h with a 4% (v/v) inoculum of 3.025 g/L L-cysteine. This is the first time that yeast has been shown to produce benzenemethanethiol isolated from the baijiu fermentation system. These findings also suggest that benzenemethanethiol can be metabolized by yeast using L-cysteine and benzaldehyde as precursor substrates.

8.
Front Oncol ; 13: 1155233, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37305571

RESUMO

Pancreatic cancer is a common type of cancer that is treated using surgery or chemotherapy. However, for patients who cannot have surgery, the treatment options are limited and have a low success rate. We report a case of a patient with locally advanced pancreatic cancer who was unable to have surgery due to a tumor that had invaded the coeliac axis and portal vein. However, after receiving chemotherapy with gemcitabine plus nab-paclitaxel(GEM-NabP), the patient achieved complete remission, and a PET-CT scan confirmed that the tumor had disappeared. Eventually, the patient underwent radical surgery with distal pancreatectomy with splenectomy, and the treatment was successful. This case is rare, and there are few reports of complete remission after chemotherapy for pancreatic cancer. This article reviews the relevant literature and guides future clinical practice.

9.
Sci Rep ; 13(1): 7756, 2023 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-37173367

RESUMO

Catalpol, a natural product mainly existed in plenty of Chinese traditional medicines, is an iridoid compound with the comprehensive effects on neuroprotective, anti-inflammatory, choleretic, hypoglycemic and anticancer. However, there are some disadvantages for catalpol such as a short half-life in vivo, low druggability, stingy binding efficiency to target proteins and so on. It is necessary to make structural modification and optimization which enhance its performance on disease treatments and clinic applications. Pyrazole compounds have been reported to have excellent anticancer activities. Based on the previous research foundation of our research group on iridoids and the anticancer activities of catalpol and pyrazole, a series of pyrazole modified catalpol compounds were synthesized by principle of drug combination for serving as potential cancer inhibitors. These derivatives are characterized by 1H NMR, 13C NMR and HRMS. The efficacy of anti-esophageal cancer and anti-pancreatic cancer activities were evaluated by the MTT assay on two esophageal cancer cells Eca-109 and EC-9706, and two pancreatic cancer cells PANC-1, BxPC-3 and normal pancreatic cell line HPDE6-C7, which showed that the compound 3e had strong inhibitory activity against esophageal cancer cells, this providing a theoretical basis for the discovery of catalpol-containing drugs.


Assuntos
Glucosídeos Iridoides , Neoplasias , Humanos , Glucosídeos Iridoides/farmacologia , Linhagem Celular , Pirazóis/química
10.
Food Res Int ; 161: 111785, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36192936

RESUMO

Pullulan-Jiuzao glutelin (JG) conjugates (PJCs) were prepared via Maillard reaction in this study. PJCs were prepared by optimizing pullulan to JG ratios (0.5:1, 1:1, 2:1, and 4:1, expressed as PJC-0.5, PJC-1, PJC-2, and PJC-4, respectively) and reaction times (0-180 min) at pH 7 and 11. The secondary structure changes of PJC compared to JG, potential conjugation sites between pullulan and JG, PJC emulsifying properties, in vitro antioxidant activities, and interaction with curcumin (CUR) were investigated. Among the four PJCs, PJC-2 obtained after 180 min reaction at pH 11 and 90 °C exhibited the best ability in nano-emulsion stabilization with the lowest particle size (180-200 nm and 290-450 nm against NaCl during storage), PDI (0.2-0.4 and 0.4-0.7 against NaCl during storage), highest zeta-potential (-20.10 mV), and lowest backscattering intensity. The spontaneous conjugation binding sites between pullulan and JG were Arg-39, Arg-54, and Asp-168. In contrast to native JG, PJC-2 exhibited better antioxidant capacities, low toxicity for CCD 841 CON and Caco-2 cells, and enhancement of antioxidant enzyme content (i.e., SOD, GPX, and CAT) after AAPH-induced oxidative stress. In addition, there exists an interaction between CUR and PJC-2 by residues Ala-74, Asp-376, Arg-368 and -374, Val-45, and Ala-44 of JG. The results above exhibit important implications for the fabrication of PJC-stabilize nano-emulsion and even for developing PJC product as a potential carrier of CUR in the functional food industry.


Assuntos
Curcumina , Antioxidantes/química , Antioxidantes/farmacologia , Células CACO-2 , Curcumina/química , Curcumina/farmacologia , Emulsões/química , Glucanos , Glutens , Humanos , Cloreto de Sódio , Superóxido Dismutase
11.
Cell Mol Gastroenterol Hepatol ; 14(5): 1146-1165, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35863742

RESUMO

BACKGROUND & AIMS: Accumulating evidence strongly suggests that hyperglycemia promotes the progression of pancreatic cancer (PC). Approximately 80% of patients with PC are intolerant to hyperglycemic conditions. In this study, we define the role of Bmi1, a stemness-related oncogene, in controlling the Warburg effect, and immune suppression under hyperglycemia conditions. METHODS: The diabetes mellitus model was established by intraperitoneal injection of streptozotocin. The role of the hyperglycemia-Bmi1-HK2 axis in glycolysis-related immunosuppression was examined in both orthotopic and xenograft in vivo models. Evaluation of immune infiltrates was carried out by flow cytometry. Human PC cell lines, SW1990, BxPC-3, and CFPAC-1, were used for mechanistic in vitro studies. RESULTS: Through bioinformatics analysis, we found that hyperglycemia was strongly related to aerobic glycolysis, immunosuppression, and cancer cell stemness. High glucose condition in the tumor microenvironment promotes immune suppression by upregulating glycolysis in PC cells, which can be rescued via knockdown Bmi1 expression or after 2-deoxy-D-glucose treatment. Through gain-/loss-of-function assessments, we found that Bmi1 upregulated the expression of UPF1, which enhanced the stability of HK2 mRNA and thereby increased the expression of HK2. The role of the hyperglycemia-Bmi-HK2 pathway in the inhibition of antitumor immunity was further verified via the immune-competent and immunodeficient mice model. We also demonstrated that hyperglycemia promotes the expression of Bmi1 by elevating the intracellular acetyl-CoA levels and histone H4 acetylation levels. CONCLUSIONS: Our results suggest that the previously unreported Bmi1-UPF1-HK2 pathway contributes to PC progression and immunosuppression, which may bring in new targets for developing effective therapies to treat patients with PC.


Assuntos
Hiperglicemia , Neoplasias Pancreáticas , Humanos , Camundongos , Animais , Estreptozocina , Acetilcoenzima A/metabolismo , Histonas/metabolismo , Neoplasias Pancreáticas/genética , Glicólise/genética , RNA Mensageiro/genética , Glucose , Camundongos Nus , Terapia de Imunossupressão , Desoxiglucose , Microambiente Tumoral , Complexo Repressor Polycomb 1/genética , Complexo Repressor Polycomb 1/metabolismo , Neoplasias Pancreáticas
12.
Food Chem ; 395: 133551, 2022 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-35802984

RESUMO

The active peptides in Qingke baijiu fermented from Qingke (highland barley) are rarely reported. This work was designed to accurately identify peptides in Qingke baijiu and evaluate their angiotensin-converting enzyme inhibitory activities in vitro. Four novel peptides, Val-Val-Thr-Gly-Val-Gly-Gly-Gln (VVTGVGGQ), Leu-Pro-Val-Gly-Pro (LPVGP), Leu-Leu-Ser-Pro-Pro (LLSPP), and Phe-Pro-Leu-Gln-Pro-His-Gln-Pro (FPLQPHQP) were identified by Nano-UPLC-MS/MS. Molecular docking showed that LPVGP and FPLQPHQP had a high affinity with ACE (binding energy -8.78, -10.02 kcal mol-1), which matched its in vitro ACE inhibitory activity (IC50 9.05, 5.03 µM). This might be related to their high hydrophobicity. Moreover, three peptides have C-terminal proline, which may contribute to their anti-digestive activity. The content of LPVGP was over 91.23% after digestion, while the content of VVTGVGGQ dropped to 55.47%. Finally, the four peptides have no obvious toxicity to Caco-2 cells. This study clarifies the ACE inhibitory activity and the structure-activity relationship of the four peptides identified in Qingke baijiu.


Assuntos
Peptidil Dipeptidase A , Espectrometria de Massas em Tandem , Sequência de Aminoácidos , Células CACO-2 , Humanos , Simulação de Acoplamento Molecular , Peptídeos/química , Peptídeos/farmacologia , Peptidil Dipeptidase A/metabolismo
13.
Food Chem ; 365: 130430, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34311281

RESUMO

Liquid-liquid microextraction (LLME) combined with gas chromatography-olfactometry-mass spectrometry (GC-O-MS) was used to detect the variations in volatile compounds during the distillation process (head, heart, and tail) of raw Baijiu produced by different layers of fermented grains; 47 aroma compounds were sniffed and identified. Moreover, temperature-programmed headspace gas chromatography-ion mobility spectrometry (TP-HS-GC-IMS) was applied to characterize the Baijiu distillation process for the first time. The 3D fingerprint spectrum clearly showed a variation in volatile compounds from different distillation stages, and most compounds showed a downward trend. In addition, multivariate statistical analysis, including principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), etc., confirmed ten aroma active markers related to classification, indicating that these markers had a great influence on the flavor of raw Baijiu.


Assuntos
Espectrometria de Mobilidade Iônica , Compostos Orgânicos Voláteis , Destilação , Cromatografia Gasosa-Espectrometria de Massas , Odorantes/análise , Olfatometria , Microextração em Fase Sólida , Temperatura , Compostos Orgânicos Voláteis/análise
14.
Food Chem Toxicol ; 155: 112402, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34246709

RESUMO

Val-Asn-Pro (VNP) was identified from the raw material of baijiu distillation (Jiupei) and exhibit antioxidant activity in vitro. In this study, residue after baijiu distillation (Jiuzao) was used to seek the antioxidant peptide VNP with the methods reported inthe previous study. Its potential antioxidant mechanism in vivo was further assessed. Gene and protein expressions of Nrf2/Keap1-p38MAPK/PI3K-MafK signaling pathway and downstream enzymes (i.e., CAT, GPX1, SOD1, and HO-1) in AAPH-induced oxidative stress Sprague-Dawley (SD) rats were investigated. Influence of VNP on baijiu characteristics was also investigated. Based on the results, VNP was identified with a content of 5.25 mg/g Jiuzao. VNP significantly mitigated excess oxidative stress via activation of Nrf2/Keap1-p38MAPK/PI3K-MafK signaling pathway and activated downstream antioxidant enzymes. Furthermore, VNP showed unconspicuous influence on the flavor and taste of baijiu when added into baijiu and the content remained stable during storage. These results indicated that VNP is a potent antioxidant component isolated from Jiuzao that can be used in baijiu to enhance its antioxidant effect without affecting the main flavor and taste. The utilization of these functional components can also increase the added value of Jiuzao.


Assuntos
Bebidas Alcoólicas , Antioxidantes/farmacologia , Oligopeptídeos/farmacologia , Adulto , Animais , Catalase/metabolismo , Feminino , Glutationa Peroxidase/metabolismo , Heme Oxigenase (Desciclizante)/metabolismo , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo/efeitos dos fármacos , Ratos Sprague-Dawley , Superóxido Dismutase-1/metabolismo , Paladar , Glutationa Peroxidase GPX1
15.
Int J Biol Macromol ; 184: 739-749, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34174310

RESUMO

Polylactic acid (PLA) is a promising food packaging material with biocompatible, nontoxic and biodegradable. In order to reduce the deterioration of aquatic products caused by microorganisms, PLA coaxial nanofiber films with cinnamaldehyde (CMA), tea polyphenol (TP) and its composite as core materials were prepared by using coaxial electrospinning technology. Its microscopic morphology and structure were characterized separately, and its thermal stability, wettability and mechanical properties were determined. The antibacterial activity and antibacterial mechanism of nanofiber films were studied with Shewanella putrefaciens (S. putrefaciens) which is the dominant spoilage of aquatic products as the target of action. The results show that the CMA/TP (m/m = 2:5)-PLA coaxial nanofibers have small diameter, uniform distribution, smooth surface, no pores and fracture. At the same time, the film has strong hydrophobicity, good thermal stability and mechanical properties. Its antibacterial performance is better than that of single-core nanofiber films, which effectively destroys the cell membrane of S. putrefaciens, increases the permeability of cell membrane, and interferes with the synthesis and expression of its protein. The coaxial nanofiber films with CMA, TP and its composite as core material can be used as a fresh-keeping material with antibacterial properties, and has potential application value in the field of food preservation.


Assuntos
Acroleína/análogos & derivados , Antibacterianos/síntese química , Poliésteres/química , Polifenóis/síntese química , Shewanella putrefaciens/efeitos dos fármacos , Chá/química , Acroleína/química , Antibacterianos/química , Antibacterianos/farmacologia , Materiais Biocompatíveis/síntese química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Estabilidade de Medicamentos , Microbiologia de Alimentos , Embalagem de Alimentos , Temperatura Alta , Interações Hidrofóbicas e Hidrofílicas , Nanofibras , Polifenóis/química , Polifenóis/farmacologia
16.
Food Funct ; 12(11): 4808-4824, 2021 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-33876788

RESUMO

Tetrapeptide Asp-Arg-Glu-Leu (DREL) was isolated from Jiuzao protein hydrolysates (JPHs) by alkaline proteinase (AP) and exhibited antioxidant activity in the HepG2 cell model in the previous study. In this study, the hydrolysis method of Jiuzao protein (JP) was further optimized by using different proteinases under different conditions (i.e., temperature, time, ratio between proteinase and substrate, and pH). Considering the limitation of in vitro assays, the AAPH-induced oxidative stress Sprague-Dawley (SD) rat model was selected to measure the antioxidant capacity of DREL in vivo. Pepsin exhibited the highest hydrolysis degree under the optimum conditions after single factor analysis (SFA) among seven proteinases. The total yield of DREL in Jiuzao was 158.24 mg kg-1Jiuzao under the pepsin's optimum hydrolysis conditions determined by response surface methodology analysis (RSMA). In addition, DREL could activate the Nrf2/Keap1-p38/PI3K-MafK signaling pathway and downstream antioxidant enzymes to improve the antioxidant ability in vivo. DREL also preliminarily exhibited anti-inflammatory activity by inhibiting the secretion of inflammatory cytokines and the mediator through the activation of Nrf2. Of note, the addition of DREL in baijiu brought an inconspicuous change in the taste after sensory evaluation. This study finds out the better proteinase used for JP hydrolysis and verifies the antioxidant capacity of DREL in vivo, which provides a potential approach to apply functional components from Jiuzao for by-product utilization. Meanwhile the antioxidant function of baijiu or other foods can be increased through adding these functional peptides without affecting the original flavor and taste in the future.


Assuntos
Antioxidantes/farmacologia , Hidrólise , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fator de Transcrição MafK/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Oligopeptídeos/farmacologia , Proteínas de Plantas/metabolismo , Animais , Células Hep G2 , Humanos , Oligopeptídeos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Proteínas de Plantas/química , Hidrolisados de Proteína/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos
17.
Am J Cancer Res ; 11(1): 123-137, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33520364

RESUMO

Increasing evidence indicates the dysregulations and pivotal roles of lncRNAs in the development and progression of various cancers, including pancreatic cancer. Enhanced glycolytic flux and epithelial-to-mesenchymal transition (EMT) have been considered as important factors in driving the malignance of pancreatic cancer. Here, we sought to evaluate the biological role and involved mechanism of lncRNA CASC9 (CASC9) in pancreatic cancer. Our present study showed that CASC9 was upregulated in various pancreatic cancer cell lines. Loss- and gain-of function of CASC9 demonstrated its critical roles in promoting the glycolysis and EMT phenotypes of pancreatic cancer. Moreover, knockdown of CASC9 inhibited the tumorigenicity and metastasis in vivo. Additionally, our findings showed that hypoxia induced the expression of CASC9 and enhanced the binding of HIF-1α to its promoter. We also demonstrated that the positive feedback loop of CASC9 and the AKT/HIF-1α signaling cascade partially mediated this biological process. Altogether, our results suggest that CASC9 promotes the glycolysis and EMT of pancreatic cancer by a positive feedback loop with AKT/HIF-1α signaling, which is synergistically enhanced by the tumor hypoxic niche. Our study will provide potential therapeutic targets for treating pancreatic cancer.

18.
Food Chem ; 347: 129028, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-33503572

RESUMO

Caoyuanwang Baijiu (CYW), a mild-flavor style Baijiu (MSB), is popular in northern China. However, there is a lack of studies reporting its aroma-active components. The aroma compounds of five CYW samples were analyzed using gas chromatography-olfactory-mass spectrometry coupled with aroma extraction dilution analysis. Fifty-five aroma-active compounds were identified in CYW, of which 27 had odor activity values ≥ 1. Reconstituted models successfully simulated the aroma profiles of CYW. The omission tests elucidated that ß-damascenone, dimethyl trisulfide, ethyl pentanoate, butanoic acid, ethyl acetate, 3-methylbutanal, ethyl lactate, hexanoic acid, γ-nonalactone, 3-hydroxy-2-butanone, ethyl butanoate, 1-propanol, 4-(ethoxymethyl)-2-methoxy-phenol, and vanillin were key odorants in CYW. The addition test confirmed the significant influence of dimethyl trisulfide on Chen-aroma note. Nine key odorants were identified as the differential quality-markers, and 85.71% key odorants were predicted using the partial least square regression (PLSR) analysis, indicating the applicability of PLSR in selecting the target compounds for omission tests.


Assuntos
Bebidas Alcoólicas/análise , Cromatografia Gasosa-Espectrometria de Massas , Odorantes/análise , Olfatometria , Compostos Orgânicos Voláteis/análise , Adulto , China , Feminino , Humanos , Masculino , Adulto Jovem
19.
Food Chem ; 330: 127257, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-32535321

RESUMO

Huangshui (HS), the by-product of Chinese Baijiu, has attracted considerable attention due to its nutrient and microbial composition; however, none of the studies has explored the polysaccharides in HS yet. Here, from HS, we isolated a novel polysaccharide, HSP-3, with an average molecular weight of 26.40 kDa. The structure was elucidated based on monosaccharide composition and methylation analysis, NMR, FT-IR, and AFM analysis. It is mainly composed of mannose (46.6%), galactose (17.3%), arabinose (11.2%), glucose (10.5%), xylose (8.2%), fucose (5.2%), and rhamnose (1.0%). The backbone of HSP-3 was made up of â†’ 2)-ß-d-Manp-(1 â†’ 2,6)-ß-d-Manp-(1 â†’ 6)-ß-d-Galp-(1 â†’ 3,6)-ß-d-Galp-(1 â†’ 4)-α-l-Rhap-(1 â†’ 3,4)-α-l-Rhap-(1 â†’ . Moreover, stimulation of the production of ROS, NO, TNF-α and IL-6, upregulation of the mRNA and protein expression levels of TNF-α and IL-6 in THP-1 cells, and enhanced the pinocytic and phagocytic capacities of THP-1 cells exhibited significant immunomodulatory properties of HSP-3. Altogether, this study suggests that HSP-3 could be used as an active component in functional foods.


Assuntos
Imunossupressores/farmacologia , Interleucina-6/metabolismo , Óxido Nítrico/biossíntese , Polissacarídeos/farmacologia , Rios/química , Fator de Necrose Tumoral alfa/metabolismo , Humanos , Imunossupressores/química , Peso Molecular , Polissacarídeos/química , Células THP-1
20.
J Sci Food Agric ; 100(1): 59-73, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31435933

RESUMO

BACKGROUND: Jiuzao is the residue after Bajiu distillation which is usually used as forage for livestock. However, it is not fully utilized yet considering the content of protein remained. The present study aimed to isolate antioxidant peptides from Jiuzao protein hydrolysates, then add these peptides into Baijiu product to enhance the healthy value of Baiju. Meanwhile environmental pollution caused by massive Jiuzao can be mitigated indirectly. RESULTS: Four peptides Ala-Tyr-Ile(Leu) (AYI(L)) and Asp-Arg-Glu-Ile(Leu) (DREI(L)) were identified from Jiuzao protein hydrolysates, the extraction contents of AYI + AYL and DREI + DREL were 896.10 and 110.51 mg kg-1 Jiuzao, respectively. On the one hand, antioxidant activities of these peptides were investigated. For in vitro antioxidant assays, AYI, AYL and DREI exhibited strong capacities in oxygen radical absorbance capacity (ORAC) assay. Furthermore, three levels of four peptides were assessed by 2,2'-azobis(2-methylpropanimidamidine) (AAPH)-induced HepG2 cells model. The results showed that these peptides exerted a degree of antioxidant activities in cells. Meanwhile, selected peptides concentrations according to cell assays remined at effective doses after in vitro digestion. On the other hand, the influence of these four peptides on the characteristic aroma compounds in Baijiu was studied. Most characteristic aroma compounds releases were increased with the addition of peptides. CONCLUSION: In the study, antioxidant activities of peptides were evaluated, the feasibility of utilizing Jiuzao protein hydrolysates to obtain beneficial peptides was also proved. Healthy effect of Baijiu or other food can be increased by adding these functional substances. The findings might contribute to food application and Baijiu industries. © 2019 Society of Chemical Industry.


Assuntos
Antioxidantes/química , Peptídeos/química , Hidrolisados de Proteína/química , Resíduos/análise , Vinho/análise , Antioxidantes/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Células Hep G2 , Humanos , Peptídeos/farmacologia , Hidrolisados de Proteína/farmacologia
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