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BACKGROUND: In our previous study, we successfully identified five peptides from wheat gluten: Ala-Pro-Ser-Tyr (APSY), Leu-Tyr (LY), Pro-Tyr (PY), Arg-Gly-Gly-Tyr (RGGY) and Tyr-Gln (YQ). Molecular docking and molecular dynamics simulation methods were employed to investigate the interaction between these antioxidant peptides and the Kelch-like ECH-associated protein 1 (Keap1 protein), revealing the molecular mechanism of their non-competitive binding. In addition, the total antioxidant capacity of the five peptides was determined using the 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) method. RESULTS: The affinities of APSY, LY, PY, RGGY and YQ were -8.9, -8.3, -8.5, -9.1 and - 7.9 kcal mol-1, respectively. The five peptides effectively bound to Keap1 protein through hydrogen, π-σ, π-alkyl and alkyl interactions. Significant roles were observed for the P1 pocket residue ARG-415 and the P3 pocket residue ALA-556 in the interactions of the Keap1-peptide complexes. Molecular dynamics simulations further elucidated the dynamic process of peptide binding to the Keap1 protein. All five peptides formed stable complexes with Keap1 protein, with van der Waals forces playing crucial roles in these complex systems, indicative of the peptides' strong binding ability to Keap1 protein. The van der Waals forces were -178.74, -123.11, -134.36, -132.59, and -121.44 kJ mol-1 for the Keap1-APSY, Keap1-LY, Keap1-PY, Keap1-RGGY and Keap1-YQ complexes, respectively. These peptides exhibited excellent antioxidant effects. Among them, the YQ peptide exhibited the highest total antioxidant capacity, with an activity value of 1.18 ± 0.06 mmol Trolox equivalent (TE) L-1 at a concentration of 0.10 mg mL-1. The RGGY, PY, LY and APSY peptides followed in descending order, with activity values of 0.91 ± 0.05, 0.72 ± 0.06, 0.62 ± 0.04 and 0.60 ± 0.05 mmol TE L-1, respectively. CONCLUSION: These results unveiled the molecular mechanism by which the five antioxidant peptides act on active pockets through the Keap1-Nrf2 signaling pathway, providing a theoretical basis for the development of antioxidants. © 2024 Society of Chemical Industry.
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In order to utilize salmon skin for high value, and investigate the structural identification and combination mechanism of iron (II)-chelating peptides systemically, Atlantic salmon (Salmo salar L.) skin, a by-product of Atlantic salmon processing, was treated by two-step enzymatic hydrolysis to obtain salmon skin active peptides (SSAP). Then they reacted with iron (II) to obtain iron (II)-chelating salmon skin active peptides (SSAP-Fe) with a high iron (II) chelating ability of 98.84%. The results of Fourier transform infrared spectroscopy (FTIR), circular dichroism (CD) spectroscopy, 8-anilino-1-naphthalenesulfonic acid ammonium salt hydrate (ANS) combined fluorescence measurement, isothermal titration calorimetry (ITC) and full wavelength ultraviolet (UV) scanning showed that the structural characteristics of SSAP changed before and after chelating iron (II). Reverse phase high performance liquid chromatography (RP-HPLC) and mass spectrometry were used to identify and quantify the peptides in SSAP-Fe. Four peptide sequences (STEGGG, GIIKYGDDFMH, PGQPGIGYDGPAGPPGPPGPPGAP and QNQRESWTTCRSQSSLPDG) were identified. The content of PGQPGIGYDGPAGPPGPPGPPGAP was the highest, at 25.17 µg/mg. The pharmacokinetic and pharmacodynamic properties of these four peptides were also investigated, and the results indicated that they have satisfactory predicted ADMET properties. Molecular docking technology was used to analyze the binding sites between iron (II) and SSAP, and it was found that PGQPGIGYDGPAGPPGPPGPPGAP had the lowest predicted binding energy with iron (II) and the most stable predicted binding energy with iron (II). This results showed that the stability of SSAP-Fe were closely related to the number of covalent bonds and the types of amino acids. This study revealed the structure and combination mechanism of SSAP-Fe, and indicated that SSAP-Fe prepared by chelation may be used as a Fe supplement that can be applied in functional foods or ingredients.
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A voltammetric immunoassay for the carcinoembryonic antigen (CEA) was developed using silver metal-organic frameworks (Ag-MOFs) as a signal probe. The Ag-MOFs contained a substantial amount of Ag(I) whose electrochemical signal was relatively stable. Therefore, the Ag-MOFs were viable signal probes. The signal can be detected without previous acid dissolution and preconcentration steps. This simplifies the detection steps and reduces the detection time. If CEA binds to its antibody on the modified electrode, the signal for Ag(I) becomes reduced. Measurements were best performed at a potential as low as 0.07 V (vs. SCE) which made the electrode hardly sensitive to potential electroactive interferents. Under optimized conditions, the method included a wide linear response range (0.05 to 120 ng mL-1) and a low detection limit of 8.0 fg mL-1 (S/N = 3). The synthesis of Ag-MOFs is relatively simple, and Ag-MOFs are not only used as nanocarriers for immobilizing anti-CEA but also acted as electroactive materials for a signal probe. The voltammetric immunoassay is stable, inexpensive, sensitive, and selective. Based on these advantages, the method holds great promise for applications in the point-of-care disease and environmental monitoring. Graphical abstract Schematic presentation of a novel electrochemical immunoassay for the carcinoembryonic antigen (CEA) using silver metal-organic frameworks (Ag-MOFs) as a signal probe.
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Antígeno Carcinoembrionário/análise , Imunoensaio/métodos , Nanopartículas Metálicas/química , Estruturas Metalorgânicas/química , Anticorpos Imobilizados/química , Anticorpos Imobilizados/imunologia , Antígeno Carcinoembrionário/imunologia , Espectroscopia Dielétrica , Técnicas Eletroquímicas , Eletrodos , Ouro/química , Humanos , Limite de Detecção , Ácidos Ftálicos/química , Prata/químicaRESUMO
BACKGROUND AND AIM: There is still controversy on the outcomes of portal vein (PV) and/or superior mesenteric vein (SMV) resection in pancreatic cancer, and there are few reports about pancreaticoduodenectomy (PD) with PV/SMV resection and reconstruction by using allogeneic vein. This study is to explore the outcomes of PD with PV/SMV resection and reconstruction by using allogeneic vein for pT3 pancreatic cancer with venous invasion. METHODS: Clinicopathological data of patients underwent PD with en bloc resection of PV/SMV and reconstruction by using internal iliac from August 20, 2013 to July 25, 2015 were collected and the data of patients with pT3 stage pancreatic head cancer with PV/SMV invasion were analyzed. The short- and long-term outcomes were presented. RESULTS: Thirty patients met the criteria of this study. PV resection and reconstruction were performed for 12 patients, SMV for 9 patients, and PV + SMV for 9 patients, respectively. The median operation time was 460 min, and the median intraoperative blood loss was 450 mL. R0 resection rate was 93.3%, total incidence of complications was 23.3%, and incidence of pancreatic fistula was 10%. The 1-year and 2-year overall survival rates were 68.6% and 39.2%, 1-year and 2-year disease free survival rates were 44.8% and 17.1%. CONCLUSIONS: PD with en bloc resection of PV/SMV and reconstruction by using allogeneic vein was safe and feasible for patients with pT3 stage pancreatic head cancer with PV/SMV invasion. A large-scale research with longer follow-up time is required to draw a significant conclusion.
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Veia Ilíaca/transplante , Veias Mesentéricas/cirurgia , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia , Procedimentos de Cirurgia Plástica/métodos , Veia Porta/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Perda Sanguínea Cirúrgica , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Veias Mesentéricas/patologia , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Duração da Cirurgia , Fístula Pancreática/etiologia , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Pancreaticoduodenectomia/efeitos adversos , Pancreaticoduodenectomia/mortalidade , Veia Porta/patologia , Procedimentos de Cirurgia Plástica/efeitos adversos , Procedimentos de Cirurgia Plástica/mortalidade , Fatores de Risco , Taxa de Sobrevida , Fatores de Tempo , Transplante Homólogo , Resultado do TratamentoAssuntos
Hepatectomia/métodos , Veia Ilíaca/transplante , Leiomiossarcoma/cirurgia , Neoplasias Vasculares/cirurgia , Procedimentos Cirúrgicos Vasculares/métodos , Veia Cava Inferior/cirurgia , Adulto , Feminino , Humanos , Imageamento Tridimensional , Leiomiossarcoma/diagnóstico , Fígado/irrigação sanguínea , Tomografia Computadorizada por Raios X , Transplante Homólogo , Neoplasias Vasculares/diagnóstico , Veia Cava Inferior/diagnóstico por imagemRESUMO
Currently, the phylogenetic relationships of Tragopogon pratensis Linnaeus (1753) remain unclear. This study presents the first report on the complete chloroplast genome of T. pratensis, which is a quadripartite structure with a length of 153,002 bp and containing a large single copy (LSC, 84,225 bp) region, a small single copy (SSC, 18,407 bp) region, a pair of inverted repeats (IR, 25,185 bp) regions. A total of 134 genes are identified, including 87 protein-coding genes, 8 rRNA genes, 37 tRNA genes, and 2 pseudogenes. Phylogenetic analysis revealed that T. pratensis is most closely related to T. dubius and that Tragopogon is a monophyletic genus.
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A novel antibacterial film based on arabinoxylan (AX) was prepared by introducing ferulic acid (FA) to AX through a laccase-catalyzed procedure. The ferulic acid-arabinoxylan conjugates (FA-AX conjugates) have been characterized. Results showed that FA was successfully grafted onto the AX chains by covalent linkages, likely through nucleophilic addition between O-Ph in the phenolic hydroxyl group of FA, or through Michael addition via O-quinone intermediates. FA-AX conjugates showed improved crystallinity, thermal stability, and rheological properties, as well as a distinct surface morphology, compared with those of native AX. Moreover, FA-AX conjugates exhibited enhanced antibacterial ability against Staphylococcus aureus, Escherichia coli, Shewanella sp., and Pseudomonas sp. Mechanistic studies revealed that the enhanced antibacterial ability was due to the penetration of bacterial membrane by the phenolic molecule and the steric effect of FA-AX conjugates. The study demonstrates that the laccase-induced grafting method was effective in producing FA-AX conjugates; we have demonstrated its antibacterial ability and great potential in prolonging the shelf life of fresh seafood products.
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Antibacterianos , Ácidos Cumáricos , Xilanos , Xilanos/química , Xilanos/farmacologia , Ácidos Cumáricos/química , Ácidos Cumáricos/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/síntese química , Lacase/química , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/crescimento & desenvolvimento , Escherichia coli/efeitos dos fármacos , Escherichia coli/crescimento & desenvolvimento , Bactérias/efeitos dos fármacosRESUMO
Background: The preoperative prognostic nutritional index (PNI) is an indicator of systemic immune-nutritional condition and is a well-known prognostic biomarker in cancer patients. This study aims to reflect the correlation between the preoperative PNI and prognosis in patients with borderline resectable pancreatic cancer (BRPC) after pancreaticoduodenectomy (PD). Methods: Medical records of patients with BRPC after PD between Jan 2011 and Dec 2021 in our hospital were retrospectively analyzed. The preoperative PNI was calculated, and the receiver operating characteristic curve was obtained based on the preoperative PNI and the 1-year survival rate. Patients were divided into two groups (High-PNI and Low-PNI) following the best cut-off value of the preoperative PNI, and demographic and pathologic findings were compared between the two groups. Univariate and multivariate analysis were performed to identify risk factors in recurrence and long-term survival. Results: The best cut-off value for the preoperative PNI was 44.6 (sensitivity: 62.46%; specificity: 83.33%; area under the curve: 0.724). Patients in the low-PNI group had significantly shorter recurrence-free survival (P=0.008) and overall survival (P=0.009). The preoperative PNI (P=0.009) and lymph node metastasis (P=0.04) were independent risk factors for tumor recurrence. The preoperative PNI (P=0.001), lymph node metastasis (P=0.04), neoadjuvant chemotherapy (P=0.04) were independent risk factors for long-term survival in patients. Conclusion: The preoperative PNI, lymph node metastasis, neoadjuvant chemotherapy were independent risk factors for recurrence and long-term survival in patients with BRPC. The preoperative PNI might be an indicator that can predict BRPC patients' recurrence and survival. Patients with high-PNI would benefit from neoadjuvant chemotherapy.
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Passively browsing other's content on social networking sites (SNS) is popular among young females. It remains unclear how passive use relates to female's negative emotions, and especially whether short-term associations are confined by individual differences. This study used ecological momentary assessment over the course of one week to examine the associations between passive use of SNS and negative emotions, and investigated whether individual differences (i.e., self-esteem and life satisfaction) would moderate this relationship. A sample of N = 99 Chinese female undergraduates (Mage = 18.81, SDage = 0.84) completed a baseline online survey on self-esteem and life satisfaction, and received a daily online survey about their Qzone use as well as their negative emotions for seven days. Multilevel modeling revealed that passively browsing Qzone on a given day was associated with less negative emotions. However, the within-person association was independent of self-esteem and life satisfaction. Implications of passive SNS use are discussed especially regarding their potential to reduce negative feelings among Chinese young female undergraduate students, at least in the short term.
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Avaliação Momentânea Ecológica , Emoções , Adolescente , Feminino , Humanos , Lactente , Autoimagem , Rede Social , Estudantes/psicologiaRESUMO
Background: Pancreatic ductal adenocarcinoma (PDAC) is known to have a poor prognosis, early local invasion, and distant metastasis. Surgical resection is the most effective treatment, and tumor recurrence can be the key factor affecting the surgical outcome. Serum carbohydrate antigen 19-9 (CA19-9) is a tumor marker with high sensitivity to pancreatic cancer; elevated CA19-9 levels often indicate poor biological behavior. Tumor size is also a crucial factor that affects the prognosis. Therefore, we developed a program to evaluate the effect of the ratio of CA19-9 to total tumor volume (CA19-9/TTV) as a prognostic marker on tumor recurrence and long-term survival in patients with PDAC following pancreaticoduodenectomy (PD). Methods: Data from 200 patients who underwent PD for PDAC were retrospectively analyzed. CA19-9/TTV was calculated according to preoperative CA19-9 and TTV, and patients were divided into two groups according to the optimal cut-off value. Univariate and multivariate analyses were performed on the clinicopathological data to screen the risk factors affecting postoperative recurrence and long-term prognosis of patients with PDAC undergoing PD. Results: The receiver operating characteristic curve showed that the best cut-off value was 5.62 (area under curve [AUC], 0.633; 95% CI: 0.548-0.718). Multivariate analysis showed that tumor differentiation and CA19-9/TTV were independent risk factors for the long-term prognosis of PDAC (P = 0.004, P = 0.007), as well as for tumor recurrence (P = 0.008, P = 0.008). Conclusion: CA19-9/TTV is an independent risk factor for the prognosis of PDAC and may be a new marker for lower survival benefits.
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Antígeno CA-19-9 , Neoplasias Pancreáticas , Biomarcadores Tumorais , Humanos , Neoplasias Pancreáticas/patologia , Prognóstico , Estudos Retrospectivos , Carga Tumoral , Neoplasias PancreáticasRESUMO
This study aimed to investigate anemia treatment and other potential effects of two food-derived bioactive oligopeptide iron complexes on pregnant rats with iron deficiency anemia (IDA) and their offspring. Rats with IDA were established with a low iron diet and then mated. There were one control group and seven randomly assigned groups of pregnant rats with IDA: Control group [Control, 40 ppm ferrous sulfate (FeSO4)]; IDA model group (ID, 4 ppm FeSO4), three high-iron groups (H-FeSO4, 400 ppm FeSO4; MCOP-Fe, 400 ppm marine fish oligopeptide iron complex; WCOP-Fe, 400 ppm whey protein oligopeptide iron complex) and three low-iron groups (L-FeSO4, 40 ppm FeSO4; MOP-Fe, 40 ppm marine fish oligopeptide iron complex; WOP-Fe, 40 ppm whey protein oligopeptide iron complex). Rats in each group were fed the corresponding special diet during pregnancy until the day of delivery. After different doses of iron supplement, serum hemoglobin, iron, and ferritin levels in rats with IDA were significantly increased to normal levels (P < 0.05). Serum iron levels were significantly lower in two food-derived bioactive oligopeptide low-iron complex groups than in the low FeSO4 group (P<0.05). Liver malondialdehyde levels were significantly increased in the three high-iron groups compared with the other five groups (P < 0.05), and hemosiderin deposition was observed in liver tissue, indicating that the iron dose was overloaded and aggravated the peroxidative damage in pregnant rats. Liver inflammation was reduced in the three low-iron groups. Tumor necrosis factor α secretion was significantly decreased in all groups with supplemented oligopeptide (P < 0.05), with the concentration of tumor necrosis factor α declining to normal levels in the two whey protein oligopeptide iron complex groups. In the marine fish oligopeptide iron complex groups, body length, tail length, and weight of offspring were significantly increased (P < 0.05) and reached normal levels. Therefore, food-derived bioactive oligopeptide (derived from marine fish skin and milk) iron complexes may be an effective type of iron supplement for pregnancy to improve anemia, as well as reduce the side effects of iron overload, and improve the growth and nutritional status of offspring.
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Micro(mi)RNAs play an essential role in the epithelial-mesenchymal transition (EMT) process in human cancers. This study aimed to uncover the regulatory mechanism of miR-1301-3p on EMT in pancreatic cancer (PC). The miRNA profilings from Gene Expression Omnibus data sets (GSE31568, GSE41372, and GSE32688) demonstrated the downregulation of miR-1301-3p in PC tissues, which was validated with 72 paired PC tissue samples through qRT-PCR detection. The low level of miR-1301-3p was associated with a poor prognosis for PC patients from the PC cohort of The Cancer Genome Atlas and the validation cohort. Gene Ontology analyses indicated that the target genes of miR-1301-3p were involved in cell cycle and adherent junction regulation. In vitro assays revealed that miR-1301-3p suppressed the proliferation and migration abilities of PC cells. Western blotting and luciferase reporter assays suggested that miR-1301-3p inhibited RhoA expression by targeting its 3'-untranslated region; RhoA upregulated N-cadherin and vimentin levels; however, it downregulated the E-cadherin level. In conclusion, our study showed that miR-1301-3p could serve as a prognostic biomarker for PC and suppress PC cell malignancy by targeting the RhoA-induced EMT process.
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BACKGROUND: Tolerance is more easily induced in liver transplant models than in other organs; CD8+CD45RClowregulatory T cells (Tregs) have been shown to induce tolerance in heart allografts. Whether CD8+CD45RClowTregs could induce tolerance in a liver transplant model and how dendritic cells (DCs) mediate the CD8+CD45RClowTregs effect remains to be investigated. METHODS: A rat liver transplantation model was established and used to test tolerance and acute rejection compared to control groups. Liver function and histopathological changes of allograft were examined by enzyme-linked immunosorbent assay (ELISA) and haematoxylin and eosin (H&E) staining, respectively. The distribution and proportion of CD8+CD45RClowTregs and plasmacytoid dendritic cells (pDCs) in the allografts and spleen were determined using flow cytometry. Cytokine secretion levels were determined using ELISA and real-time quantitative PCR (qRT-PCR). RESULTS: The rat liver transplantation model was well established, with a success rate of 93.3% (28/30). The mean survival time of the tolerant and acute-rejection rats were 156 and 14 days, respectively. The proportions of CD8+CD45RClowTegs were higher in the allografts of tolerant rats than in those of acute-rejection rats (33.1 ± 4.3 and 12.4 ± 4.6, respectively; P = 0.04). Significant accumulation of pDCs was observed in tolerant liver graft rats compared to that in acute-rejection rats (1.46 ± 0.23 and 0.80 ± 0.20, respectively; P = 0.02). Importantly, CD8+CD45RClowTregs were positively associated with the frequency of pDCs (P = 0.001, r2 = 0.775). The protein and mRNA expression of IL-10 and TGF-ß in the allograft group were increased, possibly being responsible for tolerance induction. CONCLUSION: CD8+CD45RClowT cells interact with pDCs through the induction of IL-10 and TGF-ß expression and are responsible for inducing immune tolerance in rat liver transplantation.
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Transplante de Fígado , Linfócitos T Reguladores , Animais , Linfócitos T CD4-Positivos , Linfócitos T CD8-Positivos , Células Dendríticas/metabolismo , Rejeição de Enxerto , RatosRESUMO
BACKGROUND: Liver transplantation (LT) is a life-saving treatment for patients with end-stage liver disease and acute liver failure. However, in-hospital death cannot be avoided. We designed this study to analyze patients' in-hospital mortality rate after LT and the factors correlated with in-hospital death. METHODS: The data of patients who received LT in our hospital between January 11, 2015, and November 19, 2019, were obtained from the China Liver Transplant Registry and medical records. The in-hospital mortality rate was calculated, and factors related to mortality, cause of death, and factors related to cause of death were analyzed by reviewing patients' data. RESULTS: A total of 529 patients who underwent cadaveric LT were enrolled in this study. Modified piggyback orthotopic LT was performed for all patients. Seventy patients died in the hospital after LT, and the in-hospital mortality rate was 13.2%. Factors including model for end-stage liver disease (MELD) score, Child-Pugh grading, intraoperative blood loss, and anhepatic phase were correlated with in-hospital death. MELD score and intraoperative blood loss were determined as the two independent risk factors of in-hospital death. The first two causes of death were infection (34.3%) and primary non-function (15.7%). Pulmonary fungal infection was the main cause of infectious death. MELD score was the independent risk factor for infectious death, and both body mass index of donors and cold ischemic time were independent risk factors of primary non-function. CONCLUSIONS: In-hospital death poses a threat to certain patients undergoing LT. Our study suggests that the main cause of in-hospital death is an infection, followed by primary non-function.
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OBJECTIVE: To investigate the influence of tolerance dendritic cells (tolDCs), generated from Bone marrow mesenchymal stem cells (BM-MSCs) treated with rapamycin (Rapa) on liver allograft survival in a rat acute liver transplantation model. METHODS: Different GM-CSF induction project was used to obtain immature DCs (imDCs), mature DCs (matDCs) or tolDCs from BM-MSCs. First, MLR was performed to analyze the activity of tolDCs on polyclonaly stimulated total T cells. Then, co-cultured imDCs, matDCs and tolDCs with CD8+T cells isolated by magnetic activated cell sorting to analyze the influence on its regulatory characteristic. Last, the established rat acute liver transplantation model were adoptive transfused with imDCs, matDCs or tolDCs isolated by anti-CD11c immunomagnetic beads. The phenotype of DC cells and level of CD8+Treg in the culture system and in vivo, the expression of CD8 and CD45RC in the tissues were analyzed by flow cytometry and immunohistochemistry, respectively. RESULTS: The loGM-CSF plus IL-4 decreased the costimulatory molecules of CD80/86 and MHC class II of DCs comparison with hiGM-CSF from BM-MSCs no matter whether stimulation by LPS (P<0.05). Rapa treated not only reduced the expression of CD80/86 and MHC class II but also down-regulated the expression of CD11c after LPS stimulation which was more obviously in tolDCs by loGM-CSF project (P<0.05). Moreover, tolDCs displayed a rather higher level of IL-10 and low level of IL-12p70 than others (P<0.01), which shown a rather lower stimulative effect on the proliferation of T cells comparison with matDCs and imDCs. Co-cultured with CD8+Treg showed an improvement on induction of CD8+TCR+CD45RC-T cells (CD8+Treg) in ex vivo. The rats transfused with tolDCs has a delayed survival benefits with high level of CD8+Tregs (P<0.01) and high expression of CD45RC in liver tissue (P<0.01) and spleen when comparison with other groups. The infused tolDCs improved a mean survival time (MST) of 32 days comparison with a MTS of 9.5 days and 15.75 days displayed by rat that per-infused with matDCs and imDCs, respectively. CONCLUSION: Rapa modified tolDCs derived from BM-MSCs reversed graft rejection by improve tolerance characteristics of CD8+CD45RC-Treg in acute liver rat transplantation.
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Medula Óssea/efeitos dos fármacos , Linfócitos T CD8-Positivos/efeitos dos fármacos , Células Dendríticas/efeitos dos fármacos , Antígenos Comuns de Leucócito/metabolismo , Células-Tronco Mesenquimais/efeitos dos fármacos , Sirolimo/farmacologia , Linfócitos T Reguladores/efeitos dos fármacos , Animais , Medula Óssea/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Células Dendríticas/metabolismo , Rejeição de Enxerto/tratamento farmacológico , Rejeição de Enxerto/metabolismo , Tolerância Imunológica/efeitos dos fármacos , Interleucina-10/metabolismo , Interleucina-12/metabolismo , Transplante de Fígado/métodos , Células-Tronco Mesenquimais/metabolismo , Ratos , Linfócitos T Reguladores/metabolismo , Transplante Homólogo/métodosRESUMO
The purpose was aimed to establish a simple computational model to predict tumor prognosis by combining neutrophil to lymphocyte Ratio (NLR) and biomarkers of oncological characteristics in patients undergoing vascular reconstructive radical resection of PDAC. The enrolled patients was divided into high or low NLR group with the cutoff value determined by the receiver operator characteristic (ROC) curve. Different vascular anastomoses were selected according to the Chaoyang classification of PDAC. Survival rates were calculated using the Kaplan-Meier and evaluated with the log-rank test. Cox risk regression model was used to analyze the independent risk factors for prognostic survival. The optimal cut-off value of NRL was correlated with the differentiation, tumor size, TNM stage and distant metastasis of advanced PDAC. A curative resection with vascular reconstructive of advanced PDAC according to Chaoyang classification can obviously improve the survival benefits. Cox proportional hazards demonstrated higher evaluated NLR, incisal margin R1 and lymphatic metastasis were the independent risk predictor for prognosis with the HR > 2, meanwhile, age beyond 55, TNM stage of III-IV or Tumor size > 4cm were also the obvious independent risk predictor for prognosis with the HR ≤ 2. The advanced PADC patients marked of RS group (3 < RS ≤ 6) showed no more than 24 months of survival time according to RS model based on the six independent risk predictors. Vascular reconstruction in radical resection of advanced PDAC improved survival, higher elevated NLR (>2.90) was a negative predictor of DFS and OS in those patients accompanying portal system invasion.
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Micro(mi)RNAs play a critical regulatory role in the progression and metastasis of pancreatic cancer (PC). In this study, we aimed to reveal the mechanisms of miR-374b-5p in regulating epithelial-mesenchymal transition (EMT) in PC. Gene Expression Omnibus datasets (GSE24279 and GSE71533) and the pancreatic ductal adenocarcinoma (PDAC) cohort of The Cancer Genome Atlas were employed to screen for potential prognostic miRNAs. The expression of miR-374b-5p was measured by quantitative real-time polymerase chain reaction (qRT-PCR) in 78 paired PDAC tissue samples. The biological effects of miR-374b-5p were investigated using in vitro and in vivo assays. Luciferase reporter assays and immunohistochemical tests were conducted to verify the interaction between miR-374b-5p and its predicted direct target, KDM5B. MiR-374b-5p was downregulated in PC tissues, and a low level of miR-374b-5p was associated with poor overall survival, greater tumor size, and more lymph node metastasis in PC. In vitro assays indicated that overexpression of miR-374b-5p suppressed the proliferation, migration, and invasion of PC cells. Mechanistically, miR-374b-5p suppressed the expression of KDM5B, which inhibited E-cadherin expression but promoted N-cadherin and vimentin expression. Finally, in vivo assays demonstrated that miR-374b-5p overexpression suppressed tumor growth and lung metastasis in PANC-1 cells. Thus, our findings indicate that miR-374b-5p could be a potential prognostic biomarker and therapeutic target for KDM5B-induced EMT in PC.
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BACKGROUND: The role of cluster of differentiation (CD)8+ regulatory T cells (Tregs) has previously been elucidated in tolerance models. Fibrinogen-like protein 2 (FGL2), that is secreted by Treg cells, which exhibited immunosuppressive functions, may alleviate acute rejection (AR). However, the precise role of CD8+ Tregs and FGL2 in the AR of rat liver transplantation remains unknown. Our previous study found that CD8+CD45RClow Tregs played crucial roles in maintaining immune tolerance. Here, we elucidated the role of CD8+ CD45RClowTreg and FGL2 in AR of rat liver transplantation. METHODS: A rat non-materialized AR of liver transplantation model was established using donors infected with no-load adeno-associated virus and adeno-associated virus expressing FGL2. RESULTS: There was an accumulation of tolerogenic CD8+CD45RClow in allografts compared with blank groups. Moreover, the proportion of CD8+CD45RClow Tregs was increased with longer survival time. Furthermore, we detected higher levels of FGL2 in the allografts infected with AAV-FGL2 in rats with AR of liver transplantation. We found that FGL2 could alleviate AR, and the survival time was prolonged in the recipients of donors infected with AAV-FGL2. CONCLUSIONS: Our data suggest that CD8+CD45RClow Tregs was accumulated in allografts. The presence of FGL2 alleviated AR and prolonged survival time in the AR of liver transplantation rat model, suggesting that FGL2 and CD8+CD45RClow Tregs may serves as novel therapeutic targets for AR in liver transplantation.
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Pancreatic adenosquamous carcinoma (PASC) - a rare pathological pancreatic cancer (PC) type - has a poor prognosis due to high malignancy. To examine the heterogeneity of PASC, we performed single-cell RNA sequencing (scRNA-seq) profiling with sample tissues from a healthy donor pancreas, an intraductal papillary mucinous neoplasm, and a patient with PASC. Of 9,887 individual cells, ten cell subpopulations were identified, including myeloid, immune, ductal, fibroblast, acinar, stellate, endothelial, and cancer cells. Cancer cells were divided into five clusters. Notably, cluster 1 exhibited stem-like phenotypes expressing UBE2C, ASPM, and TOP2A. We found that S100A2 is a potential biomarker for cancer cells. LGALS1, NPM1, RACK1, and PERP were upregulated from ductal to cancer cells. Furthermore, the copy number variations in ductal and cancer cells were greater than in the reference cells. The expression of EREG, FCGR2A, CCL4L2, and CTSC increased in myeloid cells from the normal pancreas to PASC. The gene sets expressed by cancer-associated fibroblasts were enriched in the immunosuppressive pathways. We demonstrate that EGFR-associated ligand-receptor pairs are activated in ductal-stromal cell communications. Hence, this study revealed the heterogeneous variations of ductal and stromal cells, defined cancer-associated signaling pathways, and deciphered intercellular interactions following PASC progression.