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1.
Acta Pharmacol Sin ; 43(6): 1360-1371, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34480113

RESUMO

Spinal cord injury (SCI) is one kind of severe trauma for central nervous system. Myelin debris clearance and axon regeneration are essential for nerve regeneration after SCI. Metformin, a glucose-lowering drug, has been demonstrated to promote the locomotor functional recovery after SCI. In this study, we investigated the role and molecular mechanism of metformin on myelin preservation in a rat SCI model. SCI was induced in rats by compression at T9 level using a vascular clip. We showed that administration of metformin (50 mg·kg-1·d-1, ip) for 28 days significantly improved locomotor function in SCI rats. Metformin also ameliorated SCI-induced neuronal apoptosis and promoted axon regeneration in the spinal cord. Using co-immunofluorescence of IBa-1 and MBP, and luxol fasting blue (LFB) staining, we demonstrated that metformin promoted the transformation of M1 to M2 phenotype polarization of microglial cells, then greatly facilitated myelin debris clearance and protected the myelin in SCI rats. Furthermore, metformin ameliorated SCI-induced blockade of autophagic flux in the spinal cord, and enhanced the fusion of autophagosome and lysosome by inhibiting the AMPK-mTOR signaling pathway. Moreover, metformin significantly attenuated inflammatory responses in the spinal cord. In LPS-treated BV2 cells, pretreatment with metformin (2 mM) significantly enhanced autophagy level, suppressed inflammation and cell apoptosis. The protective effects were blocked in the presence of an autophagy inhibitor 3-methyladenine (3-MA, 5 mM), suggesting that the effect of metformin on autophagy in microglial cells is essential for the myelin preservation during nerve recovery. This study reveals a novel therapeutic effect of metformin in SCI recovery by regulating the activation of microglial cells and enhancing its autophagy level.


Assuntos
Metformina , Traumatismos da Medula Espinal , Animais , Axônios/metabolismo , Metformina/farmacologia , Metformina/uso terapêutico , Microglia , Bainha de Mielina/metabolismo , Regeneração Nervosa , Ratos , Ratos Sprague-Dawley , Recuperação de Função Fisiológica , Medula Espinal/metabolismo , Traumatismos da Medula Espinal/tratamento farmacológico
2.
Acta Pharmacol Sin ; 42(3): 347-360, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33462377

RESUMO

DL-3-n-Butylphthalide (DL-NBP), a small molecular compound extracted from the seeds of Apium graveolens Linn (Chinese celery), has been shown to exert neuroprotective effects due to its anti-inflammatory, anti-oxidative and anti-apoptotic activities. DL-NBP not only protects against ischemic cerebral injury, but also ameliorates vascular cognitive impairment in dementia patients including AD and PD. In the current study, we investigated whether and how DL-NBP exerted a neuroprotective effect against diabetes-associated cognitive decline (DACD) in db/db mice, a model of type-2 diabetes. db/db mice were orally administered DL-NBP (20, 60, 120 mg· kg-1· d-1) for 8 weeks. Then the mice were subjected to behavioral test, their brain tissue was collected for morphological and biochemical analyses. We showed that oral administration of DL-NBP significantly ameliorated the cognitive decline with improved learning and memory function in Morris water maze testing. Furthermore, DL-NBP administration attenuated diabetes-induced morphological alterations and increased neuronal survival and restored the levels of synaptic protein PSD95, synaptophysin and synapsin-1 as well as dendritic density in the hippocampus, especially at a dose of 60 mg/kg. Moreover, we revealed that DL-NBP administration suppressed oxidative stress by upregulating Nrf2/HO-1 signaling, and increased brain-derived neurotrophic factor (BDNF) expression by activating PI3K/Akt/CREB signaling in the hippocampus. These beneficial effects of DL-NBP were observed in high glucose-treated PC12 cells. Our results suggest that DL-NBP may be a potential pharmacologic agent for the treatment of DACD.


Assuntos
Benzofuranos/uso terapêutico , Disfunção Cognitiva/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Disfunção Cognitiva/etiologia , Dendritos/efeitos dos fármacos , Diabetes Mellitus Tipo 2/complicações , Hipocampo/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Teste do Labirinto Aquático de Morris/efeitos dos fármacos , Células PC12 , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Sinapses/efeitos dos fármacos
3.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 36(10): 1235-1240, 2016 10.
Artigo em Zh | MEDLINE | ID: mdl-30641013

RESUMO

Objective To observe the inhibitory effect of Jinlongshe Granule drug-containing serum (JG-DS) on tube formation, migration, and apoptosis of human lymphatic endothelial cells ( HLECs) in vitro. Methods JG-DS was prepared. The 3rd-passage HLECs were divided into the control group (cultured with normal saline containing serum) and the experimental group (cultured with JG-DS). After cultured for 12 h, the tube formation ability was detected by Matrigel assay, and the migration ability was determined by Transwell assay in the two groups. Cell apoptosis rate was detected by flow cytometry and Annexin-V-FITC/Pl staining method. Results The total length of tube was (3 084. 49 ?326. 27) p.m after acted by 10% JG-DS for 12 h, significantly shorter than that of the control group (7 058.93 ?4 567. 39) pm (P <0.01). The migration number of HLECs was (99 ?26), obviously lower than that of the control group (160 ?32; P <0.05). The apoptosis rate of the two groups was not statistically significant (P >0.05). Conclusion JG could inhibit the tube formation and migration of HLECs in vitro, which might be one of mechanisms for inhibiting tumor micro-lymphatics.


Assuntos
Apoptose , Movimento Celular , Medicamentos de Ervas Chinesas , Células Endoteliais , Apoptose/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Proliferação de Células , Células Cultivadas , Medicamentos de Ervas Chinesas/farmacologia , Células Endoteliais/efeitos dos fármacos , Humanos
4.
Guang Pu Xue Yu Guang Pu Fen Xi ; 36(5): 1389-95, 2016 May.
Artigo em Zh | MEDLINE | ID: mdl-30001012

RESUMO

The UV-B radiation on the surface of our planet has been enhanced due to gradual thinning of ozone layer. The change of solar spectrum UV-B radiation will cause damage to all kinds of terrestrial plants at certain degree. In this paper, taking breeding sorghum (Sorghum bicolor (L.Moench))variety Longza No.5 as sample, 40 µW·cm-2 UV-B radiation treatment was conducted on sorghum seedlings at two-leaf and one-heart stage and different time courses; then after a 2 d recovering, photosynthetic parameters were measured with a photosynthetic apparatus; the activities of antioxidant enzymes were detected as well. Our results revealed that, as the dosages of UV-B increasing, leaf browning injury was aggravated, plants dwarfing and significantly were reduced fresh weight and dry weight were observed; anthocyanin content was significantly increased; chlorophyll and carotenoid content significantly were reduced and net photosynthetic rate and chlorophyll fluorescence parameters were decreased. Meanwhile, with the increase in UV-B dosages, stomatal conductance, intercellular CO2 concentration and transpiration rate showed "down - up - down" trend; the activities of SOD and GR presented "down - up" changes; activities of POD and CAT demonstrated "down - up - down", and APX, GPX showed an "up - down - up" pattern. It is worth to note that, under the four-dose treatment, a sharp decline in net photosynthesis in sorghum seedlings was observed at 6 h UV-B treatment (equals to 2.4 J·m-2), and an obvious turning point was also found for other photosynthetic parameters and activities of antioxidant enzymes at the same time point. In summary, the results indicated that the enhanced UV-B radiation directly accounted for the damages in photosynthesis system including photosynthetic pigment content, net photosynthetic rate and chlorophyll fluorescence parameters of sorghum; the antioxidant system showed different responses to UV-B radiation below or above 6 h treatment: ASA-GSH cycle was more sensitive to low-dose UV-B radiation, while high-dose UV-B radiation not only undermined the photosynthesis system, but also triggered plant enzymatic and non-enzymatic antioxidant systems, resulting in leaf browning and necrosis,biomass accumulation reduction, plant dwarfing and even death.


Assuntos
Sorghum , Antioxidantes , Biomassa , Clorofila , Fotossíntese , Folhas de Planta , Plântula , Raios Ultravioleta
5.
Zhong Yao Cai ; 38(12): 2568-72, 2015 Dec.
Artigo em Zh | MEDLINE | ID: mdl-27352540

RESUMO

OBJECTIVE: To investigate the protective mechanism of Corydalis yanhuso and L-THP in morphine-dependent gastrointestinal injury rats. METHODS: 180 male rats were randomly divided into nine groups, 20 rats for each group: saline group (N), model group (M), NS treatment group and three different dosage of Corydalis yanhusuo and L-THP groups (low dose group,middle dose group and high dose group). The rat CPP (conditioned place preference) model was established by injecting the rats with an increasing dosage of morphine, all groups received CPP training in a black compartments and white ones (drug-paired compartment) for ten days. At 48 h after the final training, the performance of CPP models were assessed to make sure all models were exported correctly. Then the treatment groups were administered with different concentration of Corydalis yanhuso (0.5, 1 and 2 g/kg) and L-THP (0.94, 1.88 and 3.76 mg/kg) for six days. All rats were immediately killed after finish the last CPP test. For each group, ten rats were killed to detect the contents of DA in the stomach and duodenum through the fluorescence spectrophotometer. The expression levels of D2 receptor( D2R) in different tissues (gastric cardia, gastric body, pylorus and duodenum) were checked by Western-blot in the other rats. RESULTS: In the NS treatment group, the time when rats stay in the white ones were significantly decreased compared with the Corydalis yanhusuo treated groups (1 and 2 g/kg) and L-THP treated groups (1.88 and 3.76 mg/kg) (P < 0.01), the high expression of DA contents in the stomach and duodenum were significantly decreased (P < 0.01). However the protein level of D2R were notably lower in gastric cardia, gastric body, pylorus and duodenum (P < 0.01). CONCLUSION: Injuries of the gastrointestinal tract followed lower DA contents and an abnormal increase of D2R in the stomach and duodenum of rats, which induced by morphine-dependent could be reversed by treatment with Corydalis yanhusuo and L-THP. This is one of mechanism underlying the protective effects of gastrointestinal tract in morphine-dependent rats.


Assuntos
Corydalis/química , Trato Gastrointestinal/efeitos dos fármacos , Dependência de Morfina/tratamento farmacológico , Morfina/farmacologia , Receptores de Dopamina D2/metabolismo , Animais , Trato Gastrointestinal/metabolismo , Ratos
6.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 33(1): 81-4, 2013 Jan.
Artigo em Zh | MEDLINE | ID: mdl-23596793

RESUMO

OBJECTIVE: To investigate the effects of Weile Powder (WLP) on bicarbonate transporters in rats with gastric ulcers, and to probe its functional mechanisms. METHODS: The 48 SD rats were randomly divided into the normal control group, the model group, the low dose WLP group (at the daily dose of 0.075 g/mL), the middle dose WLP group (at the daily dose of 0.150 g/mL), the high dose WLP group (at the daily dose of 0.030 g/mL), and the ranitidine group (at the daily dose of 0.030 g/mL), 8 in each group. The gastric ulcer rat model was prepared by the glacial acetic acid cauterization method. Rats in each medication group were administered from the 2nd day of modeling. Rats were sacrificed after 14-day successive medication. The protein was extracted from the ulcer tissue. The protein expressions of solute carrier26A3 (SLC26A3)and solute carrier26A6 (SLC26A6) were detected using Western blot. The gastric ulcer and its peripheral tissue were sectioned. The changes of cystic fibrosis transmembrane conductance regulator (CFTR) were measured by immunofluorescence. RESULTS: Compared with the model control group, the expression levels of SLC26A3 increased in the high dose WLP group and the ranitidine group with statistical difference (P < 0.05). The expression levels of SLC26A6 increased in the high and middle dose WLP groups and the ranitidine group with statistical difference (P < 0.05). The expression level of CFTR also obviously increased in the high and middle dose WLP groups (P < 0.01). CONCLUSION: WLP could elevate the expression levels of SLC26A6, SLC26A3, and CFTR, increase the secretion of bicarbonate, thus protecting the gastric mucosa.


Assuntos
Antiporters/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Mucosa Gástrica/metabolismo , Úlcera Gástrica/metabolismo , Animais , Bicarbonatos/metabolismo , Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo , Feminino , Mucosa Gástrica/efeitos dos fármacos , Masculino , Ratos , Ratos Sprague-Dawley , Transportadores de Sulfato
7.
Genomics Proteomics Bioinformatics ; 20(5): 928-938, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36464123

RESUMO

Identification of cancer driver genes plays an important role in precision oncology research, which is helpful to understand cancer initiation and progression. However, most existing computational methods mainly used the protein-protein interaction (PPI) networks, or treated the directed gene regulatory networks (GRNs) as the undirected gene-gene association networks to identify the cancer driver genes, which will lose the unique structure regulatory information in the directed GRNs, and then affect the outcome of the cancer driver gene identification. Here, based on the multi-omics pan-cancer data (i.e., gene expression, mutation, copy number variation, and DNA methylation), we propose a novel method (called DGMP) to identify cancer driver genes by jointing directed graph convolutional network (DGCN) and multilayer perceptron (MLP). DGMP learns the multi-omics features of genes as well as the topological structure features in GRN with the DGCN model and uses MLP to weigh more on gene features for mitigating the bias toward the graph topological features in the DGCN learning process. The results on three GRNs show that DGMP outperforms other existing state-of-the-art methods. The ablation experimental results on the DawnNet network indicate that introducing MLP into DGCN can offset the performance degradation of DGCN, and jointing MLP and DGCN can effectively improve the performance of identifying cancer driver genes. DGMP can identify not only the highly mutated cancer driver genes but also the driver genes harboring other kinds of alterations (e.g., differential expression and aberrant DNA methylation) or genes involved in GRNs with other cancer genes. The source code of DGMP can be freely downloaded from https://github.com/NWPU-903PR/DGMP.


Assuntos
Neoplasias , Humanos , Neoplasias/genética , Multiômica , Variações do Número de Cópias de DNA , Medicina de Precisão , Genômica/métodos , Redes Reguladoras de Genes , Redes Neurais de Computação
8.
Artigo em Inglês | MEDLINE | ID: mdl-35832528

RESUMO

A higher incidence of female infertility has been reported with an unexpectedly early appearance in recent years. The female infertility treatment and application of assisted reproductive technology have recently gained immense interest from scientists. Many studies have discussed the beneficial effects of acupuncture on female infertility. With advancements in science and medical technology, acupuncture-related research has increased in investigating its effectiveness in treating female infertility. This review focuses on a compilation of research in recent years on acupuncture for female infertility treatment and the exploration of the underlying mechanism. For this purpose, literature was searched using various search engines like PubMed, Web of Science, and Google Scholar. The search was refined by only focusing on recent studies on acupuncture effectiveness and mechanism in female infertility and evaluating pregnancy outcomes.

9.
ACS Omega ; 7(35): 30816-30822, 2022 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-36092571

RESUMO

Heavy crude oil exhibits very complex viscoelastic behaviors due to its complex composition of resins, asphaltenes, saturates, and aromatics. It has a great influence on oil production and transportation. In this work, the viscoelastic behaviors of three different heavy crude oils were measured using a rotational rheometer. In conclusion, all of these heavy crude oils display linear viscoelastic behaviors in the experimental range. The loss modulus (E″) of the three crude oils decreased as the experimental temperature increased, and the variation trends of the three crude oils were basically the same. However, the experimental temperature has almost no effect on the storage modulus (E'), which always retained a constant value of 0.4 Pa. Furthermore, the storage modulus (E') and loss modulus (E″) increase as the angular frequency increases. To describe the physical deformation characteristics of viscoelastic materials, the generalized Maxwell model and the fractional derivative Maxwell model are used to establish the constitutive relation of heavy crude oil. In conclusion, the generalized Maxwell model and the fractional derivative Maxwell model can predict the experimental results very well. All of the square of the correlation coefficient (R 2) values are greater than 0.95. However, the number of fitting parameters for the fractional derivative Maxwell model is less than that for the fourth-order generalized Maxwell model which can save the calculating time. Therefore, the fractional derivative Maxwell model is suggested to describe the viscoelastic behavior of heavy crude oil in industrial applications.

10.
J Integr Med ; 20(4): 355-364, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35249836

RESUMO

OBJECTIVES: Ziyin Huatan Recipe (ZYHT), a traditional Chinese medicine comprised of Lilii Bulbus, Pinelliae Rhizoma, and Hedyotis Diffusa, has shown promise in treating gastric cancer (GC). However, its potential mechanism has not yet been clearly addressed. This study aimed to predict targets and molecular mechanisms of ZYHT in treating GC by network pharmacology analysis and to explore the role of ZYHT in GC both in vitro and in vivo. METHODS: Targets and molecular mechanisms of ZYHT were predicted via network pharmacology analysis. The effects of ZYHT on the expression of metastasis-associated targets were further validated by Western blot and quantitative real-time polymerase chain reaction. To explore the specific molecular mechanisms of the effects of ZYHT on migration and invasion, the runt-related transcription factor 3 (RUNX3) gene was knocked out by clustered regularly interspaced short palindromic repeats/Cas9, and lentiviral vectors were transfected into SGC-7901 cells. Then lung metastasis model of GC in nude mice was established to explore the anti-metastasis effect of ZYHT. Western blot and immunohistochemistry were used to explore the impact of ZYHT on the expression of metastasis-related proteins with or without RUNX3 gene. RESULTS: The network pharmacology analysis showed that ZYHT might inhibit focal adhesion, migration, invasion and metastasis of GC. ZYHT inhibited the proliferation, migration and invasion of GC cells in vitro via regulating the expression of metastasis-associated targets. Knocking out RUNX3 almost completely reversed the cell phenotypes (migration and invasion) and protein expression levels elicited by ZYHT. In vivo studies showed that ZYHT inhibited the metastasis of GC cells to the lung and prolonged the survival time of the nude mice. Knocking out RUNX3 partly reversed the metastasis of GC cells to the lung and the protein expression levels elicited by ZYHT. CONCLUSION: ZYHT can effectively inhibit the invasion and migration of GC in vitro and in vivo, and its molecular mechanism may relate to the upregulation of RUNX3 expression.


Assuntos
Neoplasias Gástricas , Animais , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , China , Regulação Neoplásica da Expressão Gênica , Camundongos , Camundongos Nus , Invasividade Neoplásica , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética
11.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 30(5): 1453-1463, 2022 Oct.
Artigo em Zh | MEDLINE | ID: mdl-36208249

RESUMO

OBJECTIVE: To investigate the clinical value of oligoclonal bands (OB) in patients with multiple myeloma (MM). METHODS: The laboratory test and clinical data of 624 newly diagnosed MM patients admitted to Blood Diseases Hospital of Chinese Academy of Medical Sciences from January 2013 to December 2019 were retrospectively analyzed, including 30 patients with OB, and the clinical characteristics, treatment effects and survival of OB and non-OB patients were analyzed and compared. RESULTS: OB occurred in 11.8% (22/187) of patients who received autologous stem cell transplantation(ASCT) and only 1.8% (8/437) of patients who did not receive ASCT (P=0.000). The median time to the appearance of oligoclonal bands was 3.2(0.6-10.5) months after transplantation. The M protein types of oligoclonal bands mainly include IgG κ, IgG λ, IgM λ and λ light chains. In the presence of oligoclonal bands, 90% of patients were evaluated as complete remission (CR) and above. There were no statistically significant differences in disease stage, tumor burden, and genetic abnormalities between OB and non-OB patients. Among the all patients, the prognosis of OB patients was significantly better than that of non-OB patients, and OB patients showed deeper disease remission (significantly higher CR rate, MRD negative rate, and longer MRD negative duration). Among patients who underwent ASCT, OB patients showed earlier immune recovery, but the depth of treatment response and survival outcomes were similar between OB and non-OB patients, it was no statistically difference. Although OB patients showed earlier immune reconstitution, this did not translate into better survival, suggesting that the better prognosis of OB patients was mainly related to deeper and durable remission rather than early immune reconstitution. Further analysis in patients who received ASCT and obtained MRD negative indicated that there was no additional survival benefit in patients with OB. CONCLUSION: The better prognosis of OB patients may be related to the deeper treatment response, but not to the early immune reconstitution. The appearance of OB is only a sign of deep remission and early immune reconstitution in patients, it cannot be translated into survival benefit of MM patients.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Humanos , Imunoglobulina G , Imunoglobulina M , Bandas Oligoclonais , Estudos Retrospectivos , Transplante Autólogo
12.
Chem Commun (Camb) ; 57(43): 5338-5341, 2021 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-33928973

RESUMO

A NaI-promoted sequential double carbon-sulfur bond formation was developed to afford sulfur-bridged imidazopyridines, using Deoxofluor as the sulfur source and requiring only 15 min at room temperature. Using this process, imidazo[1,5-a]pyridines could also be transformed to 1,2,4-thiadiazoles in the presence of ammonium salt with the formation of both carbon-sulfur and nitrogen-sulfur bonds. This mechanistically unique method is distinguished by its wide substrate scope, lack of requirement for transition metals and mild conditions.

13.
Cell Mol Gastroenterol Hepatol ; 12(2): 395-425, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33676046

RESUMO

BACKGROUND & AIMS: Rev-erbα represents a powerful transcriptional repressor involved in immunity. However, the regulation, function, and clinical relevance of Rev-erbα in Helicobacter pylori infection are presently unknown. METHODS: Rev-erbα was examined in gastric samples from H pylori-infected patients and mice. Gastric epithelial cells (GECs) were isolated and infected with H pylori for Rev-erbα regulation assays. Gastric tissues from Rev-erbα-/- and wild-type (littermate control) mice or these mice adoptively transferred with CD4+ T cells from IFN-γ-/- and wild-type mice, bone marrow chimera mice and mice with in vivo pharmacological activation or inhibition of Rev-erbα were examined for bacteria colonization. GECs, CD45+CD11c-Ly6G-CD11b+CD68- myeloid cells and CD4+ T cells were isolated, stimulated and/or cultured for Rev-erbα function assays. RESULTS: Rev-erbα was increased in gastric mucosa of H pylori-infected patients and mice. H pylori induced GECs to express Rev-erbα via the phosphorylated cagA that activated ERK signaling pathway to mediate NF-κB directly binding to Rev-erbα promoter, which resulted in increased bacteria colonization within gastric mucosa. Mechanistically, Rev-erbα in GECs not only directly suppressed Reg3b and ß-defensin-1 expression, which resulted in impaired bactericidal effects against H pylori of these antibacterial proteins in vitro and in vivo; but also directly inhibited chemokine CCL21 expression, which led to decreased gastric influx of CD45+CD11c-Ly6G-CD11b+CD68- myeloid cells by CCL21-CCR7-dependent migration and, as a direct consequence, reduced bacterial clearing capacity of H pylori-specific Th1 cell response. CONCLUSIONS: Overall, this study identifies a model involving Rev-erbα, which collectively ensures gastric bacterial persistence by suppressing host gene expression required for local innate and adaptive defense against H pylori.


Assuntos
Imunidade Adaptativa , Infecções por Helicobacter/imunologia , Helicobacter pylori/fisiologia , Interações Hospedeiro-Patógeno/imunologia , Imunidade Inata , Membro 1 do Grupo D da Subfamília 1 de Receptores Nucleares/metabolismo , Estômago/microbiologia , Adulto , Idoso , Antígenos de Bactérias/metabolismo , Antígenos CD/metabolismo , Proteínas de Bactérias/metabolismo , Movimento Celular , Contagem de Colônia Microbiana , Células Epiteliais/metabolismo , Células Epiteliais/microbiologia , Células Epiteliais/patologia , Feminino , Mucosa Gástrica/metabolismo , Mucosa Gástrica/microbiologia , Mucosa Gástrica/patologia , Infecções por Helicobacter/sangue , Infecções por Helicobacter/microbiologia , Humanos , Sistema de Sinalização das MAP Quinases , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Células Mieloides/metabolismo , NF-kappa B/metabolismo , Proteínas Associadas a Pancreatite/metabolismo , Estômago/patologia , Células Th1/imunologia , Adulto Jovem , beta-Defensinas/metabolismo
14.
Nanomedicine ; 6(2): 371-81, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19699319

RESUMO

In this study a new chitosan (CS) derivative, galactosylated chitosan (GC), was synthesized and used to prepare norcantharidin-associated GC nanoparticles (NCTD-GC NPs) by taking advantage of the ionic cross-linkage between the molecules of the anti-hepatocarcinoma medicine NCTD and of the GC as carrier. NCTD-GC NPs were obtained with average particle size of 118.68 +/- 3.37 nm, entrapment efficiency of 57.92 +/- 0.40%, and drug-loading amount of 10.38 +/- 0.06%. Several important factors influencing the entrapment efficiency, drug-loading amount, and particle size of NCTD-GC NPs were studied. The characteristics of sustained and pH-sensitive release of NCTD from NCTD-GC NPs in vitro were studied. In addition, in vitro cellular uptake and cytotoxicity of nanoparticles to hepatoma cell lines SMMC-7721 and HepG2 were also investigated. In vitro, and compared to CS-based NCTD-CS NPs, NCTD-GC NPs demonstrated satisfactory compatibility with hepatoma cells and strong cytotoxicity against hepatocellular carcinoma cells. In vivo antitumor activity of NCTD-GC NPs was evaluated in mice bearing H22 liver tumors. NCTD-GC NPs displayed tumor inhibition effect in mice, better than either the free NCTD or the NCTD-CS NPs. As a hepatocyte-targeting carrier, GC NPs are potentially promising for clinical applications. FROM THE CLINICAL EDITOR: In this paper, a galactosylated chitosan (GC), was synthesized and norcantharidin (NCTD)-associated galactosylated chitosan nanoparticles (NCTDGC NPs) were generated by coupling NCTD--an anti-hepatocarcinoma drug--and GC as carrier. Compared to chitosan nanoparticles, NCTD-GC-NPs demonstrated satisfactory compatibility with hepatoma cells and strong cytotoxicity against the cells.


Assuntos
Compostos Bicíclicos Heterocíclicos com Pontes/química , Carcinoma Hepatocelular/tratamento farmacológico , Quitosana/química , Portadores de Fármacos/química , Galactose/química , Neoplasias Hepáticas/tratamento farmacológico , Nanopartículas/uso terapêutico , Animais , Carcinoma Hepatocelular/diagnóstico , Linhagem Celular Tumoral , Neoplasias Hepáticas/diagnóstico , Camundongos , Nanopartículas/química
15.
ACS Omega ; 5(28): 17787-17800, 2020 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-32715265

RESUMO

At present, most researches on gas-liquid two-phase flow use a power-law fluid model. However, with the development of unconventional petroleum resources and the restarting of heavy oil, the fluid showed strong yield characteristics. The power-law constitutive will not be able to express the yield-pseudoplastic fluid rheological properties. In order to make the study applicable to a larger range of shear rates, this study used the Herschel-Bulkley fluid model to discuss the gas-liquid flow characteristics. Based on the Herschel-Bulkley fluid constitutive, a two-fluid model, combined with dimensionless and iterative calculation methods, was used to theoretically derive the prediction model of liquid holdup and pressure drop for gas-liquid stratified flow. The effects of non-Newtonian fluid rheological parameters, flow conditions, and pipeline geometry on Herschel-Bulkley fluid and gas stratified flow were further analyzed. The results show that the power-law index n and the yield stress τ0 (characterizing the rheological characteristics of the liquid phase) have significant effects on the gas-liquid two-phase stratified flow. Specifically, the enhanced liquid yield and shear thinning characteristics will lead to an increase in liquid holdup and a decrease in pressure drop. Comparing with the experimental data, the calculation model proposed in this work has a good prediction effect and provides new insights into the flow behavior of gas and waxy heavy oil with yield stress.

16.
ACS Omega ; 5(34): 21443-21450, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32905271

RESUMO

The T-junction is a novel type of separator used in the petroleum and gas industry. It is used to achieve the gas-liquid or liquid-liquid two-phase separation. To obtain an applicative T-junction separator, in the present study, the gas-liquid two-phase separation characteristics in multiple inclined T-junctions were investigated through a series of numerical simulations and field experiments. Two representative multiphase modes, namely, the Euler model and the mixture model, were chosen for this study. Comparisons of the field experiments were made to obtain a highly accurate simulation model. The mixture model was chosen to be better suited for this study. It is used to investigate the gas-liquid two-phase flow and the separation behaviors, which include the effect of inlet flow velocity, inlet bubble diameter, and the split ratio of two outlets. The results indicate that the best flow split ratio exists when the two-phase separation reaches the best consequence, and the best flow split ratio changes when the separation demands of gas or liquid are different. Furthermore, the separation efficiency keeps decreasing as the inlet velocity is increased. Hence, the inlet mixture velocity should be reduced to improve the gas-liquid two-phase separation. More specifically, to obtain a better separation for the same throughput, the size of the T-junction should be increased. Moreover, the separation efficiency increases as the inlet bubble diameter increases. Consequently, the results can be used to design the T-junction as an industrial separator, which can then be directly used in petroleum and gas production.

17.
ACS Omega ; 5(48): 31332-31341, 2020 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-33324844

RESUMO

To study the flow characteristics of water and oil in a free surface vortex with an oil slick on the water surface, the flow phenomenon was simulated using FLUENT software and compared with the experimental phenomenon. The volume of the fluid model was used to obtain the oil-gas-water three-phase eddy current field, yielding the flow structure and evolution process of the free surface vortex. The results reveal that the oil and water distribution follows a specific rule, from the beginning of the vortex at the free surface, through continuous downward extension and finally reaching stability. A few other parameters were also calculated, including the vertical distribution of the vortex core radius, the maximum tangential velocity and the radial velocity at the vortex core radius, and the variation of the velocity components of each phase in the flow field with position and time. The research reveals the oil transportation characteristics of free surface vortices and provides a method for recovering an oil slick using its surface vortex characteristics.

18.
ACS Omega ; 5(48): 31262-31271, 2020 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-33324836

RESUMO

An experimental study on the flow behavior of crude oil containing sand and air in a vertical pipe with 50 mm diameter was carried out. The experiments were conducted under the following input superficial phase velocities: oil from 0.1 to 2.23 m/s and gas from 0 to 0.34 m/s. Oil was blended with sand in three different volume concentrations, namely, 0.7, 2, and 3%. Two different types of sand were used to investigate the effect of sand size distribution. A comparison between rheological measurements and pipe flow data showed that the stress-strain relationship obtained by the rheometer could be used to predict the transport characteristics in the vertical pipe flow. It was demonstrated that a small gas injection and sand addition can decrease the total pressure and friction pressure gradients. In the oil flow, the injection of air generally increased the friction factor compared to the single-phase flow, especially at low Reynolds numbers. However, the friction factor decreased by adding a small amount of fine sand. The accuracy of the correlation developed in this study was compared with other three correlations widely used in gas-liquid vertical pipe flow.

19.
World J Gastroenterol ; 26(40): 6141-6162, 2020 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-33177790

RESUMO

The gut-brain axis is a bidirectional information interaction system between the central nervous system (CNS) and the gastrointestinal tract, in which gut microbiota plays a key role. The gut microbiota forms a complex network with the enteric nervous system, the autonomic nervous system, and the neuroendocrine and neuroimmunity of the CNS, which is called the microbiota-gut-brain axis. Due to the close anatomical and functional interaction of the gut-liver axis, the microbiota-gut-liver-brain axis has attracted increased attention in recent years. The microbiota-gut-liver-brain axis mediates the occurrence and development of many diseases, and it offers a direction for the research of disease treatment. In this review, we mainly discuss the role of the gut microbiota in the irritable bowel syndrome, inflammatory bowel disease, functional dyspepsia, non-alcoholic fatty liver disease, alcoholic liver disease, cirrhosis and hepatic encephalopathy via the gut-liver-brain axis, and the focus is to clarify the potential mechanisms and treatment of digestive diseases based on the further understanding of the microbiota-gut- liver-brain axis.


Assuntos
Sistema Nervoso Entérico , Microbioma Gastrointestinal , Síndrome do Intestino Irritável , Encéfalo , Humanos , Fígado
20.
World J Clin Cases ; 7(23): 3915-3933, 2019 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-31832394

RESUMO

Organic anion transporters (OATs) and organic anion transporter polypeptides (OATPs) are classified within two SLC superfamilies, namely, the SLC22A superfamily and the SLCO superfamily (formerly the SLC21A family), respectively. They are expressed in many tissues, such as the liver and kidney, and mediate the absorption and excretion of many endogenous and exogenous substances, including various drugs. Most are composed of 12 transmembrane polypeptide chains with the C-terminus and the N-terminus located in the cell cytoplasm. OATs and OATPs are abundantly expressed in the liver, where they mainly promote the uptake of various endogenous substrates such as bile acids and various exogenous drugs such as antifibrotic and anticancer drugs. However, differences in the locations of glycosylation sites, phosphorylation sites, and amino acids in the OAT and OATP structures lead to different substrates being transported to the liver, which ultimately results in their different roles in the liver. To date, few articles have addressed these aspects of OAT and OATP structures, and we study further the similarities and differences in their structures, tissue distribution, substrates, and roles in liver diseases.

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