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1.
Biomed Pharmacother ; 124: 109883, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32004938

RESUMO

Intestinal mucositis causes great suffering to cancer patients who undergo chemotherapy and radiotherapy. Owing to the uncertain side effects of anticancer drugs to attenuate patients' intestinal mucositis, many studies focused on traditional Chinese medicine (TCM). Patchouli alcohol (PA) is an active compound extracted from Pogostemon cablin, and has potent gastrointestinal protective effect. However, whether PA has an effect on intestinal mucositis is still unknown. Therefore, we established a rat model of intestinal mucositis via intraperitoneal injection of 5-fluorouracil, and intragastrically administrated PA (10, 20, and 40 mg/kg) to evaluate the effect of PA on intestinal mucositis. The routine observation (body weight, food intake, and diarrhea) in rats was used to detect whether PA had an effect on intestinal mucositis. Levels of inflammatory cytokines (TNF-α, IL-1ß, IL-6, IL-10, and MPO), mucosal barrier proteins (zonula occludens -1 (ZO-1), claudin-1, occludin, myosin light chain (MLC), and mucin-2) and intestinal microbiota were determined to elucidate the underlying mechanism of PA action on intestinal mucositis in rats. The results showed that PA could effectively improve body weight, food intake, and diarrhea in intestinal mucositis rats, preliminary confirming PA efficacy. Further experiments revealed that PA not only decreased the levels of TNF-α, IL-1ß, IL-6, and MPO but also increased the level of IL-10 significantly. In addition, the expression of mucosal barrier proteins and microbiota community were also improved after PA treatment in diseased rats. Hence, PA may prevent the development and progression of intestinal mucositis by improving inflammation, protecting mucosal barrier, and regulating intestinal microbiota.

3.
Soft Matter ; 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31998925

RESUMO

Graphene has been studied extensively owing to its excellent lubricity performance. However, when used as lubricant additives, graphene layers tend to agglomerate and precipitate; further, poor dispersion will reduce the lubrication performance. Herein, graphene was evenly dispersed in Triton X-100/1-alkyl-3-methylimidazole ditrifluorosulfonylimide (CnmimNTf2)/H2O (n = 8, 12, and 16) lamellar liquid crystals (LLCs). The effects of the graphene concentration on the microstructures of the LLCs are detected by 2H NMR and small angle X-ray scattering measurements and their rheological and tribological performance are investigated in detail. The addition of 0.30 mg mL-1 graphene into the Triton X-100/C16mimNTf2/H2O LLC system led to a 15% reduction in the friction coefficient and 65% reduction in the wear volume when compared with the pure LLCs. The synergistic effect of the graphene and LLC hybrid system efficiently improved the lubrication performance, which is attributed to the higher order of the amphiphilic molecules and the thicker amphiphilic bilayer. The generated tribofilm formed by the physical adsorption and the tribochemical reaction of LLCs on the surface of steel is conducive to lubricity protection from abrasion. This study reveals that with the understanding of the microstructure change mechanism, the combination of graphene and LLCs could provide a new path to the design of a novel lubricant that can be utilized in nanostructures for energy saving applications.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31950217

RESUMO

Although the carbendazim is widely used to manage spot blight in celery cultivation, information on residues identified is of interest. In this study, we examined the dissipation and residual amounts of carbendazim in celery and soil under different cultivation methods when using the suggested dose and ten times of that and the bioconcentration factor of carbendazim for celery. The results showed that when celery leaves were sprayed with the suggested dose, the half-lives in a celery field and greenhouse were 2.75 days and 3.29 days, respectively. When the soil matrix was sprayed with the recommended dose before cultivation, the half-lives of carbendazim residues were 16.86 days and 11.97 days. We also conducted a long-term dietary risk assessment using the corresponding criteria. The results showed that, in China, the use of carbendazim at a dose of 0.022 g/m2 is safer and more reasonable when the harvest interval is 28 days.

5.
J Neuroinflammation ; 17(1): 34, 2020 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-31980031

RESUMO

BACKGROUND: Chronic pain usually accompanied by tissue damage and inflammation. However, the pathogenesis of chronic pain remains unclear. METHODS: We investigated the role of nerve growth factor (NGF) in chronic inflammatory pain induced by complete Freund's adjuvant (CFA), explored the methylation status of CpG islands in the promoter region of the NGF gene, and clarified the function and mechanism of C/EBPα-NGF signaling pathway from epigenetic perspective in the chronic inflammatory pain model. RESULTS: CFA induced significant hyperalgesia and continuous upregulation of NGF mRNA and protein levels in the L4-6 dorsal root ganglions (DRGs) in rats. Hypomethylation of CpG islands occurred in the NGF gene promoter region after CFA treatment. At the same time, the miR-29b expression level was significantly increased, while the DNA methyltransferase 3b (DNMT3b) level reduced significantly. Moreover, CFA treatment promoted binding of C/EBPα to the NGF gene promoter region and C/EBPα siRNA treatment obviously decreased expression of NGF levels and also alleviate inflammatory hyperalgesia significantly in rats. CONCLUSION: Collectively, the results indicated that CFA leads to the upregulation of miR-29b level, which represses the expression of DNMT3b, enhances the demethylation of the NGF gene promoter region, and promotes the binding of C/EBPα with the NGF gene promoter, thus results in the upregulation of NGF gene expression and maintenance of chronic inflammatory pain.

7.
Dig Liver Dis ; 52(2): 199-204, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31320303

RESUMO

BACKGROUND: Seroconversion of hepatitis B e antigen (HBeAg) is a critical event in the natural course of hepatitis B virus (HBV) infection. AIM: We herein characterize the virological factors associated with postpartum spontaneous HBeAg seroconversion. METHODS: A total of 214 pregnant women positive for both hepatitis B surface antigen (HBsAg) and HBeAg were followed up at 7-12 months postpartum. RESULTS: Of the subjects, 26 (12.1%) achieved spontaneous HBeAg seroconversion. Receiver operating curve analysis indicated that HBV DNA level <1.0 × 107 IU/mL, HBsAg <1.0 × 104 IU/mL and HBeAg <7.36 × 102 S/CO each independently predicted HBeAg seroconversion within 12 months postpartum. At delivery, 73.1% (19/26) women with postpartum HBeAg seroconversion had precore (PC) and/or basal core promoter (BCP) mutations, higher than that (5/36, 13.9%) in the women without postpartum seroconversion. Binary logistic regression analysis indicated that the presence of mutations in PC, BCP, and both PC and BCP at delivery was associated with an increased likelihood (OR = 13.286, 16. 238, and 22.143 respectively, all P < 0.05) to undergo postpartum spontaneous HBeAg seroconversion. CONCLUSION: These results suggest that quantitative determination of virological markers and sequencing PC and BCP can predict spontaneous HBeAg seroconversion, which could be valuable in deciding antiviral therapy against HBV.

8.
J Ethnopharmacol ; 250: 112519, 2020 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-31883475

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Pogostemon cablin, commonly named "Guang-Huo-Xiang" in China, has long been renowned for its ability to dispel dampness and regulate gastrointestinal functions. Patchouli oil (P.oil), the major active fraction of Pogostemon cablin, has been traditionally used as the principal component of Chinese medicinal formulae to treat exterior syndrome and diarrhea. However, the effects of P.oil in treating 5-fluorouracil (5-FU)-induced intestinal mucositis have not yet been reported. AIM OF THE STUDY: To investigate the protective effects of P.oil against 5-FU-induced intestinal mucositis and the mechanisms underlying these effects. MATERIALS AND METHODS: Sprague-Dawley rats were intraperitoneally injected with 5-FU (30 mg/kg) to establish an intestinal mucositis model. Meanwhile, rats with intestinal mucositis were orally administered with P.oil (25, 50, and 100 mg/kg). Histological analysis, ELISA (for detecting inflammatory cytokines and aquaporins), immunohistochemistry analysis (for examining caspases), qRT-PCR analysis (for assessment tight junctions), and western blotting analysis (for the assessment of TLR2/TLR4-MyD88 and VIP-cAMP-PKA signaling pathway-related proteins) were performed to estimate the protective effects of P.oil against intestinal mucositis and the mechanisms underlying these effects. RESULTS: The histopathological assessment preliminarily exhibited that P.oil alleviated the 5-FU-induced damage to the intestinal structure. After P.oil administration, the elevation of the expression of cytokines (TNF-α, IFN-γ, and IL-13) decreased markedly and the activation of NF-κB and MAPK signaling was significantly inhibited. P.oil also increased the mRNA expression of ZO-1 and Occludin, thereby stabilizing intestinal barrier. In addition, P.oil decreased the expressions of caspase-8, caspase-3, and Bax, and increased the expression of Bcl-2, thereby reducing the apoptosis of the intestinal mucosa. These results were closely related to the regulation of the TLR2/TLR4-MyD88 signaling pathway. It has been indicated that P.oil possibly protected the intestinal barrier by reducing inflammation and apoptosis. Furthermore, this study showed that P.oil inhibited the abnormal expression of AQP3, AQP7, and AQP11 by regulating the VIP-cAMP-PKA signaling pathway. Furthermore, it restored the intestinal water absorption, thereby alleviating diarrhea. CONCLUSIONS: P.oil ameliorated 5-FU-induced intestinal mucositis in rats via protecting intestinal barrier and regulating water transport.

9.
Eur J Pharm Sci ; 143: 105179, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31841696

RESUMO

Fibroblast growth factor receptor 1 (FGFR1) is one of the attractive pharmaceutical targets for cancer therapy. The FGFR1 targeting antagonist peptides, especially of the short peptides harbouring only coding amino acid might highlights promising aspects for their higher affinity, specificity and lower adverse reactions. However, most of peptides inhibitors remain in preclinical research, likely associating with their instability and short half-life. In this study, we found a stable short peptide inhibitor P48 and speculated that its stability might be related to its non-linear spatial structure. In addition, P48 could target the extracellular immunoglobulin domain of FGFR1, and effectively block the particular signaling pathways of FGFR1, which lead to the inhibition of cancer proliferation, invasion in vitro and restraint of tumor growth in vivo. Together, this study provided a promising FGFR1 inhibitor with the potential to be developed as an antitumor drug.

10.
J Chem Phys ; 151(21): 214105, 2019 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-31822070

RESUMO

We propose a fuzzy global optimization (FGO) algorithm to identify the lowest-energy structure of nanoclusters. In contrast to traditional methods implemented in the real space, FGO utilizes mostly the discrete space in a fuzzy search framework. Starting from random initial configurations, we carry out directed Monte Carlo and surface Monte Carlo in the discrete space to obtain low-energy candidate clusters and make real-space local optimizations finally to get the real global minimum structure. The performance of FGO is demonstrated in a large set of standard Lennard-Jones (LJ) clusters with up to 1000 atoms. All the putative global minima reported in the literature are successfully obtained with a low scaling of CPU time with cluster size, and new global minimum structures for LJ clusters with 894, 974, and 991 atoms are identified. Due to the unbiased nature, FGO can potentially deal with the global optimization of other nanomaterials with high efficiency and reliability.

11.
Sci Rep ; 9(1): 19890, 2019 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-31882811

RESUMO

Necrotizing enterocolitis (NEC) is a leading cause of mortality in preterm newborns. Intestinal barrier dysfunction is one key event in NEC pathogenesis. Human ß-defensin-3 (hBD3), one member of cationic host defence peptides, was reported to reduce the development of necrotizing enterocolitis in a neonatal rat model. And autophagy was induced in the intestine of human and animals with NEC. We hypothesized that regulation of autophagy might play a critical role in hBD3-mediated protection against NEC injury. Autophagy activity was evaluated both in intestinal epithelial cells and in NEC models. Newborn Sprague-Dawley rats were divided randomly into four groups: Control + NS, Control + rapamycin, NEC + NS, and NEC + hBD3. Body weight, histological score, survival time, enterocyte migration and mucosal barrier were recorded. Our results showed that hBD3 pretreatment could effectively inhibit autophagy activity in cultured IEC-6 and Caco2 enterocytes, and CXCR4 might be involved in hBD3-mediated autophagy suppression. Moreover, hBD3-induced inhibition of autophagy significantly promoted the intestinal epithelial cell migration by wound healing assay and transwell migration assay. In the rat model of NEC, hBD3 could noticeably reduce the expression of autophagy-activated proteins, down-regulate the expression of inflammatory mediators, and promote the mucosal integrity. Our data suggest an additional role of hBD3-mediated protection against intestinal mucosal injury: inhibition of over-activated autophagy in enterocytes.

12.
Transpl Int ; 2019 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-31868986

RESUMO

There is no large data analysis reporting the outcome of Chinese kidney transplant patients using mycophenolate mofetil (MMF). This study analyzed 6719 patients from the Chinese Scientific Registry of Kidney Transplantation using MMF, which included 1153 from donation after cardiac death (DCD), 1271 from donation after brain and cardiac death (DBCD), and 4295 from living donor (LD). Compared with the transplants from deceased donor (DD), better outcomes including 3-year graft survival probabilities (LD = 95.8% vs. DD = 91.3%), incidence of delayed graft function (DGF, LD = 2.4% vs. DD = 17.7%), infection (LD = 10.7% vs. DD = 20.7%), graft loss (LD = 2.3% vs. DD = 6.3), and death (LD = 1.3% vs. DD = 3.2%) were shown in the LD group, with similar incidences of acute rejection (AR, LD = 3.7% vs. DD = 4.7%), hyperuricemia (LD = 21.7% vs. DD = 22.2%) within postoperative 1 year, and serum creatinine (Scr) >133 µmol/l at 1 year (LD = 18.8% vs. DD = 18.6%). Nonsignificant differences were found between the DCD and DBCD group. The 5-year survival of patient and graft in the LD group were 97.5% and 93.0%. Adjusted Cox model for graft loss showed significant associations with DGF [hazard ratio 3.7 (95% CI: 2.4, 5.8)], AR [2.8 (1.7, 4.6)], Scr >133 µmol/l at 1 year [2.6 (1.5, 4.2)], hyperuricemia [2.3 (1.6, 3.3)], and DD [1.6 (1.1, 2.4)].

13.
Nutrients ; 11(12)2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31766692

RESUMO

n-3 Polyunsaturated fatty acid binding phospholipids (n-3 PUFA-PLs) are known to be potent carriers of n-3 PUFAs and provide health benefits. We previously prepared n-3 PUFA binding phosphatidylglycerol (n-3 PUFA-PG) by phospholipase D-mediated transphosphatidylation. Because PG has excellent emulsifiability, n-3 PUFA-PG is expected to work as a functional molecule with properties of both PG and n-3 PUFAs. In the present study, the health benefits and tissue accretion of dietary n-3 PUFA-PG were examined in diabetic/obese KK-Ay mice. After a feeding duration over 30 days, n-3 PUFA-PG significantly reduced the total and non-HDL cholesterols in the serum of diabetic/obese KK-Ay mice. In the mice fed n-3 PUFA-PG, but not n-3 PUFA-TAG, hepatic lipid content was markedly alleviated depending on the neutral lipid reduction compared with the SoyPC-fed mice. Further, the n-3 PUFA-PG diet increased eicosapentaenoic acid and docosahexaenoic acid (DHA) and reduced arachidonic acid in the small intestine, liver, perirenal white adipose tissue, and brain, and the ratio of the n-6 PUFAs to n-3 PUFAs in those tissues became lower compared to the SoyPC-fed mice. Especially, the DHA level was more significantly elevated in the brains of n-3 PUFA-PG-fed mice compared to the SoyPC-fed mice, whereas n-3 PUFA-TAG did not significantly alter DHA in the brain. The present results indicate that n-3 PUFA-PG is a functional lipid for reducing serum and liver lipids and is able to supply n-3 PUFAs to KK-Ay mice.

14.
Onco Targets Ther ; 12: 6789-6795, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31686837

RESUMO

Background: It has been reported that lncRNA DSCAM-AS1 plays an oncogenic role in breast cancer. In the present study we explored the role of DSCAM-AS1 in colorectal adenocarcinoma (CRA).Methods: Gene expression was analyzed by qPCR and Western blot. Overexpression experiments were performed to analyze gene interactions. Transwell assays were performed to analyze cell invasion and migration. Methylation-specific PCR (MSP) was performed to analyze DNA methylation. Results: It was observed that DSCAM-AS1 was upregulated in the primary tumor tissues than in paired non-tumor tissues (within 2 cm around tumors) and was further increased with tumor metastasis. miR-216b was downregulated in primary tumor and further downregulated with tumor metastasis. miR-216b was inversely correlated with DSCAM-AS1 in tumor tissues, but not in non-tumor tissues. In cells of CRA cell lines, DSCAM-AS1 overexpression resulted in the downregulation of miR-216b, while miR-216b overexpression did not significantly affect DSCAM-AS1. DSCAM-AS1 overexpression did not significantly affect cancer cell proliferation but promoted cell migration and invasion. miR-216b inhibited cancer cell migration and invasion and significantly reduced the effects of DSCAM-AS1 overexpression. Methylation-specific PCR showed that DSCAM-AS1 overexpression promoted the methylation of miR-216b gene. Conclusion: DSCAM-AS1 may downregulate miR-216b to promote the migration and invasion of CRA cells.

15.
J Org Chem ; 84(23): 15508-15519, 2019 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-31671942

RESUMO

A visible-light catalyzed [3 + 1 + 2] annulation for the synthesis of unsymmetrical trisubstituted amino-1,3,5-triazines from amidines, isothiocyanates, and 1,1,3,3-tetramethylguanidines has been developed. This method exhibits the advantages of easily available starting materials, insensitive to air and moisture, wide substrate scopes, high step economy, mild, metal- and ligand-free conditions, which has potential applications in the organic, medicinal, and material chemistry.

16.
Mol Med ; 25(1): 47, 2019 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-31706267

RESUMO

BACKGROUND: The hunt for the molecular markers with specificity and sensitivity has been a hot area for the tumor treatment. Due to the poor diagnosis and prognosis of pancreatic cancer (PC), the excision rate is often low, which makes it more urgent to find the ideal tumor markers. METHODS: Robust Rank Aggreg (RRA) methods was firstly applied to identify the differentially expressed genes (DEGs) between PC tissues and normal tissues from GSE28735, GSE15471, GSE16515, and GSE101448. Among these DEGs, the highly correlated genes were clustered using WGCNA analysis. The co-expression networks and molecular complex detection (MCODE) Cytoscape app were then performed to find the sub-clusters and confirm 35 candidate genes. For these genes, least absolute shrinkage and selection operator (lasso) regression model was applied and validated to build a diagnostic risk score model. Cox proportional hazard regression analysis was used and validated to build a prognostic model. RESULTS: Based on integrated transcriptomic analysis, we identified a 19 gene module (SYCN, PNLIPRP1, CAP2, GNMT, MAT1A, ABAT, GPT2, ADHFE1, PHGDH, PSAT1, ERP27, PDIA2, MT1H, COMP, COL5A2, FN1, COL1A2, FAP and POSTN) as a specific predictive signature for the diagnosis of PC. Based on the two consideration, accuracy and feasibility, we simplified the diagnostic risk model as a four-gene model: 0.3034*log2(MAT1A)-0.1526*log2(MT1H) + 0.4645*log2(FN1) -0.2244*log2(FAP), log2(gene count). Besides, a four-hub gene module was also identified as prognostic model = - 1.400*log2(CEL) + 1.321*log2(CPA1) + 0.454*log2(POSTN) + 1.011*log2(PM20D1), log2(gene count). CONCLUSION: Integrated transcriptomic analysis identifies two four-hub gene modules as specific predictive signatures for the diagnosis and prognosis of PC, which may bring new sight for the clinical practice of PC.

17.
Tuberculosis (Edinb) ; 119: 101880, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31731061

RESUMO

Mycobacterium tuberculosis (MTB) serine proteases are important pathogen-associated virulence factors that are involved in the invasion, bacterial persistence, and degradation of host defense factors. The current study identified and characterized a novel serine protease, Rv3194c, of MTB. A heterologous Rv3194c protein, purified from Escherichia coli, possessed proteolytic activity that could hydrolyze bovine serum albumin (BSA), milk, casein, and gelatin at an optimal temperature of 40 °C and a pH of 8.0. Furthermore, the divalent metal ions Ca2+ and Mn2+ increased the activity of Rv3194c. Betulinic acid, a Traditional Chinese Medicine (TCM) monomer; PMSF, a chemical inhibitor; and the Roche inhibitor cocktail inhibited proteolytic activity. Site-directed mutagenesis demonstrated that D308 and particularly S309 play a crucial role in the catalytic activity of Rv3194c protease. The cellular assays revealed that Rv3194c inhibits THP1-derived macrophage migration. Moreover, Rv3194c degraded the complement components, C3b and C5a, causing inhibition of phagocytosis and chemotaxis. In mice, Rv3194c enhanced the persistence of Mycobacterium smegmatis (Ms) in the lung, induced lung lesions, and promoted the release of inflammatory cytokines. The results of this study indicate that Rv3194c may play an important role in the pathogenicity of mycobacteria.

18.
Medicine (Baltimore) ; 98(45): e17920, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31702672

RESUMO

There is little information concerning the predictive ability of the preoperative platelet to albumin ratio (PAR) in hepatocellular carcinoma (HCC) patients after liver resection. In the current study, we aimed to assess the prognostic power of the PAR in HCC patients without portal hypertension (PH) following liver resection.Approximately 628 patients were included in this study. A receiver operating characteristic (ROC) curve analysis was performed to evaluate the predictive value of the PAR for both recurrence-free survival (RFS) and overall survival (OS). Univariate and multivariate analyses were used to identify the independent risk factors for both RFS and OS.During the follow-up period, 361 patients experienced recurrence, and 217 patients died. ROC curve analysis suggested that the best cut-off value of the PAR for RFS was greater than 4.8. The multivariate analysis revealed that microvascular invasion (MVI), tumor size >5 cm, high aspartate aminotransferase-to-platelet count ratio index (APRI) and high PAR were four independent risk factors for both RFS and OS. Patients with a low PAR had significantly better RFS and OS than those with a high PAR.The PAR may be a useful marker to predict the prognosis of HCC patients after liver resection. HCC patients with a high preoperative PAR had a higher recurrent risk and lower long-term survival rate than those with a low preoperative PAR.


Assuntos
Albuminas/metabolismo , Plaquetas/metabolismo , Carcinoma Hepatocelular/mortalidade , Neoplasias Hepáticas/mortalidade , Recidiva Local de Neoplasia/epidemiologia , Adulto , Biomarcadores/sangue , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Feminino , Hepatectomia/mortalidade , Hepatectomia/estatística & dados numéricos , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Valor Preditivo dos Testes , Período Pré-Operatório , Intervalo Livre de Progressão , Curva ROC
19.
Front Pharmacol ; 10: 1134, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31632274

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is currently the most common chronic hepatic disorder worldwide. The earliest stage of NAFLD is simple steatosis, which is characterized by the accumulation of triglycerides in hepatocytes. Inhibition of steatosis is a potential treatment for NAFLD. Patchouli alcohol (PA) is an active component of Pogostemon cablin (Blanco) Benth. (Labiatae), which is a medicinal food in Asia countries and proved to possess hepatoprotective effect. This research aimed to investigate the effectiveness of PA against high fat diet (HFD)-induced hepatic steatosis in rats. In this study, male Sprague Dawley rats were fed a HFD for 4 weeks to induce NAFLD. Oral administration with PA significantly reduced pathological severity of steatosis in HFD-fed rats. It was associated with suppressing endoplasmic reticulum (ER) stress and regulating very low-density lipoprotein (VLDL) metabolism. Our data showed that PA treatment effectively attenuated ER stress by inhibiting the activation of protein kinase-like ER kinase (PERK), inositol-requiring transmembrane kinase/endoribonuclease 1 (IRE1), and activating transcription factor 6 (ATF6). Moreover, PA decreased hepatic VLDL uptake by suppressing very low-density lipoprotein receptor (VLDLR) expression. It also restored VLDL synthesis and export by increasing apolipoprotein B100 (apoB 100) secretion and microsomal triglyceride-transfer protein (MTP) activity. Taken together, PA exerted a protective effect on the treatment of NAFLD in HFD-fed rats and may be potential therapeutic agent acting on hepatic steatosis.

20.
Int J Oncol ; 55(6): 1249-1260, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31638165

RESUMO

The purpose of the present study was to compare metabolites from formalin­fixed and paraffin­embedded (FFPE) pancreatic tissue blocks with those identified in optimal cutting temperature (OCT)­embedded pancreatic tissue blocks. Thus, ultra­performance liquid chromatograph­mass spectrometry/mass spectrometry­based metabolic profiling was performed in paired frozen (n=13) and FFPE (n=13) human pancreatic adenocarcinoma tissue samples, in addition to their benign counterparts. A total of 206 metabolites were identified in both OCT­embedded and FFPE tissue samples. The method feasibility was confirmed through reproducibility and a consistency assessment. Partial least­squares discriminant analysis and heatmap analysis reliably distinguished tumor and normal tissue phenotypes. The expression of 10 compounds, including N­acetylaspartate and creatinine, was significantly different in both OCT­embedded and FFPE tumor samples. These ten compounds may be viable candidate biomarkers of malignant pancreatic tissues. The super­categories to which they belonged exhibited no significant differences between FFPE and OCT­embedded samples. Furthermore, purine, arginine and proline, and pyrimidine metabolism used a shared pathway found in both OCT­embedded and FFPE tissue samples. These results supported the notion that metabolomic data acquired from FFPE pancreatic cancer specimens are reliable for use in retrospective and clinical studies.

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