RESUMO
Pancreatic regeneration after acute pancreatitis is critical in the normal restoration of pancreatic exocrine function, the inhibition of which can cause severe complications including pancreatic exocrine insufficiency. However, the regulators of pancreatic regeneration and the underlying mechanisms remain uncovered. Here, using the inducible Tet-on system, we found that regenerating family member 4 (Reg4) knockdown significantly impaired pancreatic regeneration after pancreatitis. Both acinar-to-ductal metaplasia and the resolution of pancreatitis during regeneration were affected by Reg4 knockdown. Further investigations confirmed that Reg4 exerted its function through regulating Notch activation both in vitro and in vivo. Our study revealed Reg4 as a new regulator and potential therapeutic target for pancreatic regeneration.
Assuntos
Proliferação de Células , Pâncreas/metabolismo , Proteínas Associadas a Pancreatite/metabolismo , Pancreatite/metabolismo , Receptores Notch/metabolismo , Regeneração , Animais , Modelos Animais de Doenças , Células HEK293 , Humanos , Masculino , Metaplasia , Camundongos Endogâmicos C57BL , Pâncreas/patologia , Pancreatite/genética , Pancreatite/patologia , Transdução de SinaisRESUMO
Mild acute pancreatitis (AP) is a self-limiting disease, whereas severe AP has high mortality because of enhanced systemic inflammation and multiple organ failure. In experimental models of AP, infiltration of monocytes and activation of monocyte-derived macrophages largely determine the severity of the disease. Our previous studies have shown that CD11b+Ly-6Chi inflammatory monocytes were mobilized from bone marrow into peripheral blood and inflamed pancreas during the early stage of AP. However, the phenotype and characteristics of circulating monocytes in patients with AP are not well defined. Fifty patients with AP and nine age- and sex-matched healthy volunteers were enrolled in this study. Compared with those of healthy volunteers, the proportion of CD14hiCD16- monocytes and the level of myeloid-related cytokines/chemokines were increased in AP patients within 48 h after disease onset, especially in patients with a severe disease course. Moreover, the increased monocyte proportions were associated with decreased HLA-DR expression and a reduced T cell count. Notably, dynamic changes in circulating CD14hiCD16- monocytes and their HLA-DR expression, as well as in CD4+ T cells, were obviously different between moderate severe AP and severe AP. Last, area under the receiver operating characteristic analysis showed that the combination of CD14hiCD16- monocyte proportions with their HLA-DR level had higher accuracy for predicting the severity of AP. Taken together, the ratio of CD14hiCD16- monocytes and their HLA-DR level might assist in predicting the severity of disease in AP patients at admission and in monitoring patients' clinical status during recovery.
Assuntos
Receptores de Lipopolissacarídeos/imunologia , Monócitos/imunologia , Pancreatite/imunologia , Receptores de IgG/imunologia , Índice de Gravidade de Doença , Adulto , Contagem de Linfócito CD4 , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD4-Positivos/patologia , Quimiocinas/sangue , Quimiocinas/imunologia , Feminino , Proteínas Ligadas por GPI/sangue , Proteínas Ligadas por GPI/imunologia , Antígenos HLA-DR/sangue , Antígenos HLA-DR/imunologia , Humanos , Receptores de Lipopolissacarídeos/sangue , Masculino , Pessoa de Meia-Idade , Monócitos/metabolismo , Monócitos/patologia , Pancreatite/sangue , Pancreatite/patologia , Valor Preditivo dos Testes , Receptores de IgG/sangueRESUMO
Severe acute pancreatitis (SAP) is a severe acute abdominal disease. Recent evidence shows that intestinal homeostasis is essential for the management of acute pancreatitis. Chitosan oligosaccharides (COS) possess antioxidant activity that are effective in treating various inflammatory diseases. In this study we explored the potential therapeutic effects of COS on SAP and underlying mechanisms. Mice were treated with COS (200 mg·kg-1·d-1, po) for 4 weeks, then SAP was induced in the mice by intraperitoneal injection of caerulein. We found that COS administration significantly alleviated the severity of SAP: the serum amylase and lipase levels as well as pancreatic myeloperoxidase activity were significantly reduced. COS administration suppressed the production of proinflammatory cytokines (TNF-α, IL-1ß, CXCL2 and MCP1) in the pancreas and ileums. Moreover, COS administration decreased pancreatic inflammatory infiltration and oxidative stress in SAP mice, accompanied by activated Nrf2/HO-1 and inhibited TLR4/NF-κB and MAPK pathways. We further demonstrated that COS administration restored SAP-associated ileal damage and barrier dysfunction. In addition, gut microbiome analyses revealed that the beneficial effect of COS administration was associated with its ability to improve the pancreatitis-associated gut microbiota dysbiosis; in particular, probiotics Akkermansia were markedly increased, while pathogenic bacteria Escherichia-Shigella and Enterococcus were almost eliminated. The study demonstrates that COS administration remarkably attenuates SAP by reducing oxidative stress and restoring intestinal homeostasis, suggesting that COS might be a promising prebiotic agent for the treatment of SAP.
Assuntos
Quitosana/uso terapêutico , Homeostase/efeitos dos fármacos , Intestinos/efeitos dos fármacos , Oligossacarídeos/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Pancreatite/tratamento farmacológico , Doença Aguda , Animais , Apoptose/efeitos dos fármacos , Quitina/análogos & derivados , Quitina/uso terapêutico , Microbioma Gastrointestinal/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Pâncreas/efeitos dos fármacos , Pâncreas/patologia , Pancreatite/patologia , Transdução de Sinais/efeitos dos fármacosRESUMO
An increase of Escherichia-Shigella was previously reported in acute necrotizing pancreatitis (ANP). We investigated whether Escherichia coli MG1655, an Escherichia commensal organism, increased intestinal injury and aggravated ANP in rats. ANP was induced by retrograde injection of 3.5% sodium taurocholate into the biliopancreatic duct. Using gut microbiota-depleted rats, we demonstrated that gut microbiota was involved in the pancreatic injury and intestinal barrier dysfunction in ANP. Using 16S rRNA gene sequencing and quantitative PCR, we found intestinal dysbiosis and a significant increase of E. coli MG1655 in ANP. Afterward, administration of E. coli MG1655 by gavage to gut microbiota-depleted rats with ANP was performed. We observed that after ANP induction, E. coli MG1655-monocolonized rats presented more severe injury in the pancreas and intestinal barrier function than gut microbiota-depleted rats. Furthermore, Toll-like receptor 4 (TLR4)/MyD88/p38 mitogen-activated protein (MAPK) and endoplasmic reticulum stress (ERS) activation in intestinal epithelial cells were also increased more significantly in the MG1655-monocolonized ANP rats. In vitro, the rat ileal epithelial cell line IEC-18 displayed aggravated tumor necrosis factor alpha-induced inflammation and loss of tight-junction proteins in coculture with E. coli MG1655, as well as TLR4, MyD88, and Bip upregulation. In conclusion, our study shows that commensal E. coli MG1655 increases TLR4/MyD88/p38 MAPK and ERS signaling-induced intestinal epithelial injury and aggravates ANP in rats. Our study also describes the harmful potential of commensal E. coli in ANP.IMPORTANCE This study describes the harmful potential of commensal E. coli in ANP, which has not been demonstrated in previous studies. Our work provides new insights into gut bacterium-ANP cross talk, suggesting that nonpathogenic commensals could also exhibit adverse effects in the context of diseases.
Assuntos
Disbiose/fisiopatologia , Escherichia coli/fisiologia , Microbioma Gastrointestinal/fisiologia , Mucosa Intestinal/microbiologia , Pancreatite Necrosante Aguda/microbiologia , Animais , Masculino , Pancreatite Necrosante Aguda/induzido quimicamente , Ratos , Ratos Sprague-Dawley , Simbiose , Ácido Taurocólico/farmacologiaRESUMO
Pancreatic cancer (PC) is an aggressive malignancy associated with a poor prognosis and low responsiveness to chemotherapy and radiotherapy. Most patients with PC have metastatic disease at diagnosis, which partly accounts for the high mortality from this disease. Here, we explored the role of the transcription factor sex-determining region Y-box (Sox) 6 in the invasiveness of PC cells. We showed that Sox6 is down-regulated in patients with PC in association with metastatic disease. Sox6 overexpression suppressed PC cell proliferation and migration in vitro and tumour growth and liver metastasis in vivo. Sox6 inhibited epithelial-mesenchymal transition (EMT), and Akt signalling. Sox6 was shown to interact with the promoter of Twist1, a helix-loop-helix transcription factor involved in the induction of EMT, and to modulate the expression of Twist1 by recruiting histone deacetylase 1 to the promoter of the Twist1 gene. Twist1 overexpression reversed the effect of Sox6 on inhibiting EMT, confirming that the effect of Sox6 on suppressing tumour invasiveness is mediated by the modulation of Twist1 expression. These results suggest a novel mechanism underlying the aggressive behaviour of PC cells and identify potential therapeutic targets for the treatment of PC.
Assuntos
Regulação Neoplásica da Expressão Gênica , Histona Desacetilase 1/genética , Neoplasias Hepáticas/genética , Proteínas Nucleares/genética , Neoplasias Pancreáticas/genética , Fatores de Transcrição SOXD/genética , Proteína 1 Relacionada a Twist/genética , Animais , Carcinogênese/genética , Carcinogênese/metabolismo , Carcinogênese/patologia , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Transição Epitelial-Mesenquimal , Histona Desacetilase 1/metabolismo , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/terapia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Invasividade Neoplásica , Proteínas Nucleares/metabolismo , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/terapia , Regiões Promotoras Genéticas , Ligação Proteica , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Fatores de Transcrição SOXD/agonistas , Fatores de Transcrição SOXD/metabolismo , Transdução de Sinais , Carga Tumoral , Proteína 1 Relacionada a Twist/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Pancreatic acinar cell necrosis and inflammatory responses are two key pathologic processes in acute pancreatitis (AP), which determines the severity and outcome of the disease. Recent studies suggest that necroptosis, a programed form of necrosis, is involved in the pathogenesis of AP, but the underlying mechanisms remain unknown. We investigated the expression of necrosome components, including receptor-interacting protein (RIP) 1, RIP3, and mixed lineage kinase domain-like (MLKL), and the molecular mechanisms in pancreatitis-associated necroptosis. We found that RIP3 and phosphorylated MLKL expression was positively related to the degree of necrosis, whereas RIP1 expression was negatively related to the degree of necrosis. Pharmacologic inhibition of RIP1 kinase activity exerted no protection against caerulein/cholecystokinin-8-induced AP, but knockdown of RIP1 with siRNA increased acinar cell necrosis and inhibition of NF-κB activation. RIP1 inhibition led to enhanced RIP3 expression. RIP3 and MLKL inhibition decreased acinar cell necrosis, in which the inhibition of RIP3 reduced the phosphorylation level of MLKL. RIP3 inhibition had no effect on trypsinogen activation but partly inhibited inflammasome activation. Our study strongly suggests that the imbalance between RIP1 and RIP3 shifts the cell death to necrosis, which unravels a new molecular pathogenesis of mechanism of AP and may provide insight into the development of novel therapeutic agent for other necrosis-related diseases.
Assuntos
Pancreatite/patologia , Proteína Serina-Treonina Quinases de Interação com Receptores/fisiologia , Células Acinares/fisiologia , Doença Aguda , Animais , Apoptose/fisiologia , Ceruletídeo/toxicidade , Colecistocinina/toxicidade , Irritantes/toxicidade , Masculino , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Necrose/fisiopatologia , Fragmentos de Peptídeos/toxicidade , Fosforilação/fisiologia , Inibidores de Proteínas Quinases/farmacologia , Ratos Sprague-Dawley , Proteína Serina-Treonina Quinases de Interação com Receptores/antagonistas & inibidores , Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismoRESUMO
OBJECTIVE: To investigate the anti-inflammatory effect and mechanisms of interleukin-35 (IL-35) in inflammatory bowel disease. METHODS: BALB/c mice were divided into three groups with 10 mice in each group:control group, model group (oral administration of 4% glucan sodium sulfate for 7 d) and IL-35-treated group (oral administration of 4% glucan sodium sulfate for 7 d, intraperitoneal injection of 2 µg IL-35 at d2-5). Disease activity index (DAI) was scored every day. After 7 d, the mice were sacrificed, and the serum and intestinal tissue samples were collected. The gross morphology of the colon was observed; HE staining was used to observe the pathological changes of colon tissue; flow cytometry was employed to detect the change of macrophage polarization ratio in colon tissue; the mRNA expression levels of cytokines IL-6, TNF-α, IFN-γ, IL-10 and SHIP1 in colon tissue were determined by real-time quantitative RT-PCR; the expression and distribution of SHIP1 in colon tissue was measured by immunohistochemistry; Western blotting was adopted to detect the expression level of SHIP1 protein in colonic intestinal tissues of each group. RESULTS: The DAI scores of the mice in the model group were higher than those in the control group, while the DAI scores in the IL-35-treated group were lower than those in the model group (all P<0.01). Compared with the control group, the colon length was significantly shortened in the model group (P<0.05), while the colon length of the IL-35-treated group had an increasing trend compared with the model group, but the difference was not statistically significant (P>0.05). Compared with the model group, microscopic inflammatory infiltration score was decreased and microscopic crypt destruction and score was significantly lower in IL-35-treated group (all P<0.05). The relative expression of proinflammatory cytokines IL-6, TNF-α and IFN-γ in the colon tissue of IL-35-treated group was decreased compared with the model group, while the relative expression of IL-10 mRNA was higher than that of the model group (all P<0.05). Compared with the control group, the proportion of M1 macrophages in the model group increased (P<0.05), while the proportion of M1 macrophages in the IL-35-treated group was lower than that in the model group (P<0.05). The relative expression of SHIP1 mRNA and protein in the colon tissue of IL-35-treated group was higher than that in the model group (all P<0.05). CONCLUSIONS: IL-35 can inhibit the polarization of M1 macrophages and regulate inflammatory cytokines to promote anti-inflammatory effect on mice with colitis.
Assuntos
Anti-Inflamatórios , Colite , Colo , Modelos Animais de Doenças , Regulação da Expressão Gênica , Interleucinas , Animais , Anti-Inflamatórios/farmacologia , Colite/tratamento farmacológico , Colite/fisiopatologia , Colo/efeitos dos fármacos , Citocinas/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Glucanos/farmacologia , Interleucina-6/genética , Interleucinas/farmacologia , Macrófagos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Fosfatidilinositol-3,4,5-Trifosfato 5-Fosfatases/genéticaRESUMO
OBJECTIVE: To investigate the therapeutic effects of quercetin on early-stage inflammation in hypertriglyceridemia (HTG)-related acute pancreatitis (AP) both in vivo and in vitro, and its possible mechanism. METHODS: In vivo, rats were fed a high-fat diet to induce HTG, and AP was induced by intraperitoneal injection of cerulein (50 µg/kg × 2). Quercetin (100, 150 and 200 mg/kg) was administered by intraperitoneal injection after AP induction. In vitro, rat exocrine acinar cells were preincubated with palmitic acid (PA, 0.1 mmol/L, 6 h) with quercetin (5, 10, 20 and 40 µM) prior to a cholecystokinin analog CCK-8 (20pM). Injury of the pancreas was assessed by amylase secretion and pancreatic histological evaluation. Inflammation was estimated by measuring IL-1ß, IL-6, TNFα and NF-kB expression. Dynamic expression of IRE1α, sXBP1, C/EBPα and C/EBPß was monitored by real-time PCR, immunofluorescence (IF) and western blot (WB). RESULTS: Quercetin intervention reduced plasma amylase level (P < 0.001) in a dose-dependent manner, attenuated pancreatic histopathological damage (P < 0.05), and reduced the mRNA and protein expression of NF-kB, IL-1ß, IL-6, TNFα (P < 0.05) more significantly in HTG-related AP rats than in normal-lipid AP rats. Quercetin also down-regulated gene and protein expression levels of IRE1α, sXBP1, C/EBPα and C/EBPß in a dose-dependent manner. CONCLUSIONS: Quercetin attenuates early-stage inflammation in HTG-related AP, probably by reducing IRE1α, sXBP1, C/EBPα and C/EBPß expression.
Assuntos
Hipertrigliceridemia/complicações , Inflamação/tratamento farmacológico , Pancreatite/tratamento farmacológico , Pancreatite/etiologia , Quercetina/uso terapêutico , Animais , Gorduras na Dieta/administração & dosagem , Gorduras na Dieta/efeitos adversos , Relação Dose-Resposta a Droga , Inflamação/patologia , Pâncreas/patologia , Pancreatite/patologia , Quercetina/administração & dosagem , Ratos , Ratos Sprague-DawleyRESUMO
AIM: To analyze the features and treatment of hypertriglyceridemia-induced acute pancreatitis (HTGP) during pregnancy. METHODS: A retrospective study of 21 pregnant women diagnosed with acute pancreatitis (AP) was performed. Patients were divided into acute biliary pancreatitis (ABP), HTGP, and idiopathic groups according to etiology. RESULTS: 95% of the patients were in the third trimester of gestation. The percentage of patients with HTGP was higher than that of ABP (48% vs.14%). The percentage of severe acute pancreatitis (SAP) in the HTGP group was higher than that in the ABP group (40.0% vs.0%). The Ranson scores for moderately severe acute pancreatitis (MSAP) and SAP in the HTGP group were significantly different (2.50 ± 0.58 vs.3.60 ± 0.89, P < 0.05, respectively). The mean serum triglyceride (TG) levels in the MSAP and SAP HTGP groups were not significantly different (18.81 ± 11.13 vs. 30.53 ± 24.20 mmol/L, P > 0.05, respectively). In the HTGP group, there were five patients given plasma exchange therapy and five not. Plasmapheresis decreased the incidence of systemic inflammatory response syndrome (SIRS) from 100% to 28.6% and the TG level from 20.36 ± 7.41 mmol/L to 5.23 ± 3.62 mmol/L (P < 0.05). The length of hospitalization of the plasmapheresis group was shorter than that of the nonplasmapheresis group (17.3 ± 6.7 days vs. 37.0 ± 20.8 days). CONCLUSIONS: Plasma exchange may be safe and effectively administered for HTGP patients during pregnancy with SIRS or multiple organ dysfunction syndrome (MODS). J. Clin. Apheresis 31:571-578, 2016. © 2015 Wiley Periodicals, Inc.
Assuntos
Hipertrigliceridemia/complicações , Pancreatite/terapia , Plasmaferese , Doença Aguda , Adulto , Feminino , Humanos , Insuficiência de Múltiplos Órgãos/prevenção & controle , Pancreatite/etiologia , Pancreatite/patologia , Segurança do Paciente , Gravidez , Estudos Retrospectivos , Síndrome de Resposta Inflamatória Sistêmica/prevenção & controle , Triglicerídeos/sangueRESUMO
OBJECTIVES: To investigate the effect of miR-183 on the cell proliferation in SW1990 pancreatic cancer cell line by targeting programmed cell death factor 4(PDCD4). METHODS: The SW1990 pancreatic cancer cells were transfected with miR-183 mimics and inhibitors at different concentrations, the alteration of PDCD4 levels was observed at specific concentrations by qPCR and Western blot. The cellular proliferation of transfected cells was determined by MTT assay. The distribution of cell cycle and apoptosis was examined by flow cytometry (FCM) and Hoechst 33258 staining. The expression of B-cell lymphoma(bcl-2) was evaluated by Western blot. RESULTS: The miR-183 mimic and inhibitor (at concentrations of 50 nmol/L or 150 nmol/L) showed significantly increasing or decreasing effects on the levels ofmiR-183 respectively. The expression of PDCD4 was downregulated in the cells transfected with miR-183 mimics, while significantly upregulated in the cells treated with miR-183 inhibitors. Western blot showed that miR-183 inhibitors resulted in a marked decrease in the expression levels of bcl-2. The growth of SW1990 cells was obviously inhibited after anti-miR-183 treatment, while an increase of apoptosis cells proportion and cell cycle G0/G1 arrest were observed after miR-183 inhibitors transfection. CONCLUSIONS: The miR-183 inhibitors could restrain cell proliferation, promote cell apoptosis and increase G0/G1 arrest in SW1990 pancreatic cancer cells, which may be possibly through targeting PDCD4.
Assuntos
Proteínas Reguladoras de Apoptose/genética , MicroRNAs/genética , Neoplasias Pancreáticas/patologia , Proteínas de Ligação a RNA/genética , Apoptose , Pontos de Checagem do Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , TransfecçãoRESUMO
Inflammation triggered by necrotic acinar cells contributes to the pathophysiology of acute pancreatitis (AP), but its precise mechanism remains unclear. Recent studies have shown that Cyclophilin A (CypA) released from necrotic cells is involved in the pathogenesis of several inflammatory diseases. We therefore investigated the role of CypA in experimental AP induced by administration of sodium taurocholate (STC). CypA was markedly upregulated and widely expressed in disrupted acinar cells, infiltrated inflammatory cells, and tubular complexes. In vitro, it was released from damaged acinar cells by cholecystokinin (CCK) induction. rCypA (recombinant CypA) aggravated CCK-induced acinar cell necrosis, promoted nuclear factor (NF)-κB p65 activation, and increased cytokine production. In conclusion, CypA promotes pancreatic damage by upregulating expression of inflammatory cytokines of acinar cells via the NF-κB pathway.
Assuntos
Ciclofilina A/metabolismo , NF-kappa B/metabolismo , Pâncreas/metabolismo , Pancreatite/metabolismo , Células Acinares/efeitos dos fármacos , Células Acinares/metabolismo , Células Acinares/patologia , Animais , Morte Celular/efeitos dos fármacos , Colecistocinina/toxicidade , Ciclofilina A/genética , Ciclofilina A/toxicidade , Citocinas/genética , Modelos Animais de Doenças , Mediadores da Inflamação/metabolismo , Masculino , Pâncreas/patologia , Pancreatite/genética , Pancreatite/patologia , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Regulação para CimaRESUMO
BACKGROUND: To identify transcription factors (TFs) and single nucleotide polymorphisms (SNPs) of Lrh1 (also named Nr5a2) and its homologous genes in Lrh1-knockout pancreas of mice. METHODS: The RNA-Seq data GSE34030 were downloaded from Gene Expression Omnibus (GEO) database, including 2 Lrh1 pancreas knockout samples and 2 wild type samples. All reads were processed through TopHat and Cufflinks package to calculate gene-expression level. Then, the differentially expressed genes (DEGs) were identified via non-parametric algorithm (NOISeq) methods in R package, of which the homology genes of Lrh1 were identified via BLASTN analysis. Furthermore, the TFs of Lrh1 and its homologous genes were selected based on TRANSFAC database. Additionally, the SNPs were analyzed via SAM tool to record the locations of mutant sites. RESULTS: Total 15683 DEGs were identified, of which 23 was Lrh1 homology genes (3 up-regulated and 20 down-regulated). Fetoprotein TF (FTF) was the only TF of Lrh1 identified and the promoter-binding factor of FTF was CYP7A. The SNP annotations of Lrh1 homologous genes showed that 92% of the mutation sites were occurred in intron and upstream. Three SNPs of Lrh1 were located in intron, while 1819 SNPs of Phkb were located in intron and 1343 SNPs were located in the upstream region. CONCLUSION: FTF combined with CYP7A might play an important role in Lrh1 regulated pancreas-specific transcriptional network. Furthermore, the SNPs analysis of Lrh1 and its homology genes provided the candidate mutant sites that might affect the Lrh1-related production and secretion of pancreatic fluid.
Assuntos
Proteínas de Ligação a DNA/genética , Regulação da Expressão Gênica/genética , Redes Reguladoras de Genes/genética , Pâncreas/metabolismo , Polimorfismo de Nucleotídeo Único/genética , Receptores Citoplasmáticos e Nucleares/genética , Receptores Citoplasmáticos e Nucleares/metabolismo , Fatores de Transcrição/genética , Animais , Colesterol 7-alfa-Hidroxilase/genética , Colesterol 7-alfa-Hidroxilase/metabolismo , Biologia Computacional , Camundongos , Camundongos Knockout , Anotação de Sequência MolecularRESUMO
OBJECTIVE: To compare the efficiency of 1.9 µm Vela Laser versus high-frequency electronic knife in the treatment of digestive tract big polyps. METHODS: A total of 30 patients with big polyps (>2 cm in diameter) hospitalized from May 2013 to November 2013 were randomly divided into two groups to receive 1.9 µm Vela Laser or high-frequency electric knife respectively. The sites of polyp were at stomach (n = 4), duodenum (n = 4), sigmoid colon (n = 12) and large intestine (n = 10).Surgical duration, outcomes, intra-operative and post-operative complications, lesion remnant and relapse possibilities were systematically reviewed to compare the efficiency of these two techniques. RESULTS: The average operating duration of high frequency electronic knife treatment was shorter than 1.9 µm Vela Laser treatment (20.9 ± 1.4 vs 27.6 ± 1.2 min).For those with high frequency electronic knife, there were obvious wound bleeding (n = 2); intra-operative perforation (n = 1) and abdominal discomforts within 24 hours post-surgery (n = 3).In contrast, none of those with 1.9 µm Vela Laser suffered the above complications. All wounds were well-healed after 6 months, except for 2 patients with high frequency electronic knife leaving an apparent scar at wound site (without significant stricture).One case had residual lesion during the multi-point biopsy. CONCLUSION: By avoiding such side-effects as bleeding, perforation and stomachache, 1.9 µm Vela Laser possesses many advantages over high frequency electronic knife.However, the former technique is in its early development period and some bottlenecks such as a longer operating duration should be urgently addressed.
Assuntos
Trato Gastrointestinal , Lasers , Pólipos , Biópsia , Humanos , Complicações Pós-Operatórias , Fatores de TempoRESUMO
Both drought stress and exogenous selenium (Se) cause changes in plant physiological characteristics, which are key factors affecting crop yield. Although Se is known to be drought-resistant for crops, its internal physiological regulatory mechanisms are not clear. This study analyzed the effects of selenium application (SeA) on antioxidant enzyme activities, osmoregulatory substance contents, and photosynthetic characteristics of greenhouse tomatoes under drought stress and related physiological mechanisms. The results showed that drought stress induced oxidative damage in cells and significantly increased the content of the membrane lipidation product malondialdehyde (MDA) and the osmoregulatory substance proline (p < 0.001) compared with the adequate water supply. The proline content of severe drought stress (W1) was 9.7 times higher than that of the adequate water supply (W3), and foliar SeA increased glutathione peroxidase (GSH-PX) activity, and SeA induced different enzymatic reactions in cells under different drought stresses; catalase (CAT) was induced under severe drought stress (p < 0.01) and was significantly increased by 32.1% compared with the clear water control, CAT. Peroxidase (POD) was induced under adequate water supply conditions (p < 0.01), which was significantly increased by 15.2%, and SeA attenuated cell membrane lipidation, which reduced MDA content by an average of 21.5% compared with the clear water control, and also promoted photosynthesis in the crop. Meanwhile, through the entropy weighting method analysis (TOPSIS) of the indexes, the highest comprehensive evaluation score was obtained for the S5W3, followed by the S2.5W3 treatment. Therefore, this study emphasized the importance of SeA to reduce oxidative damage and enhance photosynthesis under drought stress.
RESUMO
Attapulgite (APT) is widely used in wastewater treatment due to its exceptional adsorption and colloidal properties, as well as its cost-effectiveness and eco-friendliness. However, low-grade APT generally limits its performance. Here, a colloid mill-assisted ultrasonic-fractional centrifugal purification method was developed to refine low-grade APT. This process successfully separated and removed impurity minerals such as quartz and dolomite from the raw ore, resulting in a refined APT purity increase from 16.9% to 60% with a specific surface area of 135.5 m2âg-1. Further modifying of the refined APT was carried out through the hydrothermal method using varying dosages of cetyltrimethylammonium chloride (CTAC), resulting in the production of four different APT adsorbents denoted as QAPT-n (n = CTAC mole number) ranging from 0.5 to 5 mmol. Using Congo red (CR) as the target pollutant, the QAPT-5 sample exhibited the best adsorption capacity with the maximum quantity of 1652.2 mgâg-1 in a neutral solution at 30 °C due to the highest surface charge (zeta potential = 8.25 mV). Moreover, the QAPT-5 pellets (~2.0 g adsorbent) shaped by the alginate-assisted molding method removed more than 96% of 200 mL aqueous solution containing 200 mgâL-1 CR and maintained this efficiency in 10 adsorption-elution cycles, which exhibited the promising practical application.
RESUMO
Phytoremediation is a low-cost, environmentally friendly, and sustainable technology that can utilize vegetation and microorganisms to avoid eutrophication and purifying water environment. The ability of five different living aquatic plants of nitrogen (N), phosphorus (P), and chemical oxygen demand (CODcr) removal were investigated in pilot scale constructed wetlands (CWs). Aquatic plant mixes significantly improved CODcr removal and plant tissue uptake of nitrogen and phosphorus. The wetland performance of mixed plantings was also influenced by the specific species. The mixed planting of Phragmites australi, Nymphaea Colorado and Myriophyllum verticillatum (PNM)When assessing pollutant removal in CWs, PNM performed better within mixtures, a possible synergistic effect, while TNV Typha orientalis, Nymphaea Colorado, and Vallisneria natans (TNV) performed poorly, a possible antagonist effect. The nutrient uptake within plant tissues byunder mixed plants planting was always ahad synergistic effect. Mixed plantingAquatic plant mixes significantly increased the rhizosphere microbial diversity and promoted the growth of functional denitrifying flora.
Assuntos
Biodegradação Ambiental , Nitrogênio , Fósforo , Rizosfera , Áreas Alagadas , Fósforo/metabolismo , Nitrogênio/metabolismo , Poluentes Químicos da Água/metabolismo , Poluentes Químicos da Água/análise , Análise da Demanda Biológica de Oxigênio , Projetos Piloto , Microbiota , Plantas/metabolismo , Nymphaea/metabolismo , Microbiologia do SoloRESUMO
The imbalance of the lateral shoulder is reflected by the clavicle angle (CA) in radiology. It remains unclear how to achieve postoperative lateral shoulder balance (LSB) after spinal deformity correction surgery. A retrospective analysis was conducted on AIS patients who underwent surgery by the same spine surgeon at our hospital from 2016 to 2020. A total of 110 patients with spinal deformity were included in the study to verify the correlation between the T1-T5 tilt angle and CA before and after surgery, as well as the relation-ship between the change in T1-T5 tilt angle before and after surgery and the change in CA before and after surgery. By comparing the correlation coefficients, it was found that there may not be a direct relationship between the pre- and postoperative tilt angles of T1-5 and CA, but their changes were closely related to the changes in CA. The change in T1 tilt angle after orthopaedic surgery was significantly correlated with the change in CA, with a correlation coefficient of 0.976, indicating a close relationship between T1 and the clavicle. As the vertebrae moved down, the correlation gradually decreased. In summary, this study suggests that there is a close relationship between T1-T5 and the clavicle and that the change in T1 tilt angle after spinal scoliosis correction surgery is significantly correlated with CA, which decreases as the vertebra moves down.
RESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Herbal formulas from Traditional Chinese Medicine are common and well-established practice for treating acute pancreatitis (AP) patients. However, little is known about their bioactive ingredients and mechanisms, such as their targets and pathways to inhibit inflammation. AIM OF THE STUDY: This study aimed to evaluate the effect of Qing Xia Jie Yi Formula (QXJYF) granules on AP and discuss the molecular mechanisms involved. MATERIALS AND METHODS: Major compounds in QXJYF granules were identified using UPLC-quadrupole-Orbitrap mass spectrometry (UPLC-Q-Orbitrap MS). The effect of QXJYF granules on experimental AP models both in vitro and in vivo, and detailed mechanisms were clarified. Two AP models were induced in mice by intraperitoneally injections of caerulein or L-arginine, and QXJYF granules were used to treat AP mice in vivo. Histological evaluation of pancreas and lung, serum amylase and lipase levels, serum inflammatory cytokines, inflammatory cell infiltration and macrophage phenotype were assessed. Bone marrow derived macrophages (BMDMs) were cultured and treated with QXJYF granules in vitro. BMDM phenotype and glycolysis levels were measured. Lastly, clinical effect of QXJYF granules on AP patients was verified. Predicted severe AP (pSAP) patients eligible for inclusion were assessed for enrollment. RESULTS: Nine major compounds were identified in QXJYF granules. Data showed that QXJYF granules significantly alleviated AP severity both in caerulein and L-arginine-induced AP models in vivo, pancreatic injury and inflammatory cell infiltration, systematic inflammation, lung injury and inflammatory cell infiltration were all improved after QXJYF treatment. QXJYF granules significantly reduced M1 macrophages during AP both in vivo and in vitro; besides, the mRNA expression levels of M1 genes such as inos, Tnfα, Il1ß and Il6 were significantly lower after QXJYF treatment in M1 macrophages. Mechanistically, we found that HK2, PFKFB3, PKM, LDHα levels were increased in M1 macrophages, but significantly decreased after QXJYF treatment. Clinical data indicated that QXJYF granules could significantly reduce CRP levels and shorten the duration of organ failure, thereby reducing the incidence of SAP and preventing pSAP patients from progressing to SAP. CONCLUSION: QXJYF granules alleviated AP through the inhibition of M1 macrophage polarization by suppressing glycolysis.
Assuntos
Pancreatite , Humanos , Camundongos , Animais , Pancreatite/metabolismo , Ceruletídeo/efeitos adversos , Doença Aguda , Inflamação/tratamento farmacológico , Macrófagos , ArgininaRESUMO
High-purity hydrogen produced by water electrolysis has become a sustainable energy carrier. Due to the corrosive environments and strong oxidizing working conditions, the main challenge faced by acidic water oxidation is the decrease in the activity and stability of anodic electrocatalysts. To address this issue, efficient strategies have been developed to design electrocatalysts toward acidic OER with excellent intrinsic performance. Electronic structure modification achieved through defect engineering, doping, alloying, atomic arrangement, surface reconstruction, and constructing metal-support interactions provides an effective means to boost OER. Based on introducing OER mechanism commonly present in acidic environments, this review comprehensively summarizes the effective strategies for regulating the electronic structure to boost the activity and stability of catalytic materials. Finally, several promising research directions are discussed to inspire the design and synthesis of high-performance acidic OER electrocatalysts.
RESUMO
BACKGROUND: Pancreatic fibrosis is a hallmark feature of chronic pancreatitis (CP), resulting in persistent damage to the pancreas. The sustained activation of pancreatic stellate cells (PSCs) plays a pivotal role in the progression of pancreatic fibrosis and is a major source of extracellular matrix (ECM) deposition during pancreatic injury. METHODS: Calpain is a calcium-independent lysosomal neutral cysteine endopeptidase and was found to be correlated to various fibrotic diseases. Studies have revealed that calpeptin, a calpain inhibitor, can improve the fibrosis process of multiple organs. This study investigated the effect of the calpain inhibitor, calpeptin, on fibrosis in experimental CP and activation of cultured PSCs in mice. CP was induced in mice by repeated injections of cerulein for four weeks in vivo, and the activation process of mouse PSCs was isolated and cultured in vitro. Then, the inhibitory effect of calpeptin on pancreatic fibrosis was confirmed based on the histological damage of CP, the expression of α-smooth muscle actin (α-SMA) and collagen-Iα1(Col1α1), and the decrease in mRNA levels of calpain-1 and calpain-2. RESULTS: In addition, it was revealed that calpeptin can inhibit the activation process of PSCs and induce significant PSCs apoptosis by downregulating the expression of calpain-1, calpain-2 and TGF-ß1, and the expression and phosphorylation of smad3 in vitro. CONCLUSION: These results suggest that the calpain inhibitor, calpeptin, plays a key role in the regulation of PSC activation by inhibiting the TGF-ß1/smad3 signaling pathway, which supports the potential of calpeptin as an inhibitor of pancreatic fibrosis in mice by interfering with calpain.