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1.
Pathol Res Pract ; 215(12): 152681, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31685298

RESUMO

The hexosamine biosynthetic pathway (HBP), a branch of glucose metabolism, provides a substrate for glycosylation modification, which has a wide-ranging effect on cellular functions. Glutamine-fructose-6-phosphate transaminase 2 (GFPT2) has been reported to regulate the HBP as the first and rate-limiting enzyme. Given the inverse association between GFPT2 expression and survival of patients with serous ovarian cancer (SOC) observed in The Cancer Genome Atlas (TCGA) database, we attempted to investigate the role of GFPT2 and its related mechanisms in SOC. The results showed that GFPT2 was over-expressed in SOC tissues, and positive correlations with advanced stage (FIGO III/IV), suboptimal removal rate and poor survival were observed in 90 SOC patients. Cell migration and invasion were also inhibited in GFPT2 knockdown SKOV3 and HEY cells. The levels of O-linked ß-N-acetylglucosamine (O-GlcNAc) and intranuclear ß-catenin were evaluated and the observed increase in O-GlcNAcylation induced by GFPT2 may contribute to epithelial-mesenchymal transition (EMT). These data provide novel insights into the function of GFPT2 and O-GlcNAcylation in the EMT and thus the invasiveness SOC.

2.
BMC Cancer ; 19(1): 1136, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31752756

RESUMO

BACKGROUND: Early recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) is associated with poor surgical outcomes. This study aims to construct a preoperative model to predict individual risk of post-LT HCC recurrence. METHODS: Data of 748 adult patients who underwent deceased donor LT for HCC between January 2015, and February 2019 were collected retrospectively from the China Liver Transplant Registry database and randomly divided into training (n = 486) and validation(n = 262) cohorts. A multivariate analysis was performed and the five-eight model was developed. RESULTS: A total of 748 patients were included in the study; of them, 96% had hepatitis B virus (HBV) and 84% had cirrhosis. Pre-LT serum alpha-fetoprotein (AFP), tumor number and largest tumor diameter were incorporated to construct the 5-8 model which can stratify patients accurately according to their risk of recurrence into three prognostic subgroups; low-(0-5 points), medium-(6-8 points) and high-risk (> 8 points) with 2-year post-LT recurrence rate of (5,20 and 51%,p <  0.001) respectively. The 5-8 model was better than Milan, Hangzhou, and AFP-model for prediction of HCC early recurrence. These findings were confirmed by the results of the validation cohort. CONCLUSIONS: The 5-8 model is a simple validated and accurate tool for preoperative stratification of early recurrence of HCC after LT.

3.
BMC Oral Health ; 19(1): 248, 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31727038

RESUMO

BACKGROUND: The aim of this study was to evaluate the clinical outcome of autotransplantation of mature third molars to fresh molar extraction sockets using 3D replicas. METHODS: Ten patients underwent teeth autotransplantation with or without GBR. We observed the mobility, percussion, radiography examination, the probing depth and the masticatory function of the transplanted teeth during 2 years following up, which were transplanted into fresh molar sockets by using 3D replicas, and GBR when it is necessary. RESULTS: The average extra-oral time of donor tooth had been shortened to 1.65 min when used the 3D replica. Some probing depth of the transplanted tooth were deeper than 3 mm at 4 or 5 weeks temporarily. And one patient felt slight sensitive when chewing with soft food at 4 weeks, then disappeared. The clinical examination of the autotransplantation teeth during 1 year follow-up showed no sign of failure. CONCLUSIONS: The tooth autotransplantation using 3D replica with or without GBR is an effective method which can reduce the extra-oral time of the donor teeth and may result in less failure.

4.
Sci Rep ; 9(1): 17006, 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31740693

RESUMO

'Quality evaluation based on color grading' is one of the features used in Chinese medicine discrimination. In order to assess the feasibility of electronic eye (E-eye) in implementing 'quality evaluation based on color grading', the present study applied an IRIS VA400 E-eye to test 58 batches of Corni Fructus samples. Their optical data were acquired and combined with their corresponding classes. A total of four quality discrimination models were produced according to discrimination analysis (DA), least squares support vector machine (LS-SVM), partial least squares-discrimination analysis (PLS-DA), and principal component analysis-discrimination analysis (PCA-DA). The accuracy rate of the aforementioned 4 cross evaluation models were 86.21%, 89.66%, 81.03% and 91.38%, respectively. Therefore, the PCA-DA method was used to build the final discrimination model for classifying Corni Fructus or discriminating its quality.

5.
J Exp Clin Cancer Res ; 38(1): 445, 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31666106

RESUMO

In the publication of our publication [1], we have noticed there is a wrong label in Fig. 1e, in which the position of "HCC" and "Adjacent" should be transposed.

6.
Int Immunopharmacol ; : 105997, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31761683

RESUMO

BACKGROUND: Hepatic ischemia reperfusion injury (IRI) is a primary cause of organ dysfunction occurring during liver resection surgery and transplantation. Galectin-1, an endogenous lectin expressed on lymphoid organs, plays an important role in governing innate and adaptive immunity. This study was designed to determine the therapeutic role of galectin-1 and underlying mechanism in hepatic IRI. METHODS: Male C57BL/6 mice were subjected to 90 min of partial hepatic ischemia followed by reperfusion with or without treatment with recombinant galectin-1 (rGal-1) or neutralizing anti-IL-10 antibody. Mice were sacrificed at 6 and 24 h following reperfusion. Liver damage related enzymes were determined and cytokines/chemokines were measured by qPCR and ELISA. RESULTS: Administration of rGal-1 significantly attenuated hepatic IRI, including a remarkable reduction in serum ALT/AST levels and an improved liver histology score compared to controls. rGal-1 treatment reduced TUNEL positive apoptotic hepatocytes, attenuated proinflammatory cytokines (TNF-α, IL-6, IL-1ß, IL-12, IFN-γ, IL-17) and chemokines (CXCL-1, CXCL-10) levels, but upregulated IL-10 expression, compared with controls. In addition, rGal-1 increased the production of IL-10 in hepatic macrophages in vivo and in vitro. Blockade of IL-10 using neutralizing anti-IL-10 antibody reversed the protection of galectin-1 in hepatic IRI in mice. CONCLUSION: These data suggest that galectin-1 may attenuate hepatic IRI via an IL-10-dependent mechanism, which is a promising therapeutic target.

7.
Math Biosci Eng ; 17(1): 627-635, 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31731368

RESUMO

Objective: To compare the 2-year efficacy and safety of combination therapy with entecavir (ETV) and adefovir dipivoxil (ADV) to that of tenofovir disoproxil fumarate (TDF) monotherapy in treatment of patients with adefovir drug-resistant chronic hepatitis B. Methods: HBeAg-positive CHB patients (n = 100) with adefovir-resistance (rtA181T/V and/or rtN236T) were enrolled. Patients were treated with either ETV 0.5 mg plus ADV 10 mg per day (n = 52) or TDF 300 mg per day (n = 48) for 48 weeks. Tests for liver and kidney function, Serum Phosphorus, HBV serum markers, HBV DNA load and ultrasonography of liver were performed every 3 months. Student's t-test and χ2 test were used to compare the efficacy, side effects in the two groups. Results: Fifty-two patients in ETV + ADV group and forty-eight patients in TDF group were followed-up for 96 weeks. HBV DNA undetectable rate were 76.9% versus 81.3% (P = 0.631) at week 48, and 92.3% versus 95.8% (P = 0.679) at week 96 in ETV + ADV combination therapy and TDF monotherapy group respectively. Serum ALT normalized rate were 84.6% versus 87.5% (P = 0.777) at week 48, and 92.3% versus 95.8% (P = 0.679) at week 96 in ETV+ADV combination therapy and TDF monotherapy group respectively. But the level of serum Phosphorus was significantly lower in ETV + ADV combination therapy group compare with TDF monotherapy group (1.13 ±0.15 versus 1.22 ±0.16, P = 0.004) at week 96. Conclusion: Both ETV + ADV combination therapy and TDF monotherapy provided effective treatments in chronic hepatitis B with adefovir-resistant. However, it was associated with poor serological responses up to week 96. The long term treatment of hepatitis B with ETV (0.5 mg/day) combination of ADV (10 mg/day) can potentially cause hypophosphatemia and renal impairment, so regular monitoring of serum phosphate, serum creatinine and evaluation of eGFR is needed.

8.
Medicine (Baltimore) ; 98(45): e17673, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31702620

RESUMO

The effect of non-jaundice stage at diagnosis on clinicopathological features and prognosis of patients with periampullary carcinomas (PACs) remains uncertain.The 504 patients who were pathologically diagnosed with PACs between 2012 and 2017 were retrospective analyzed. Kaplan-Meier method was used to estimate survival and log-rank tests were used for comparisons between groups.Patients were divided into the non-jaundice group and the jaundice group according to serum total bilirubin (3 mg/dL) at diagnosis. By comparison with the jaundice group, more patients of the non-jaundice group manifested abdominal pain with longer duration. The degree of deterioration of complete blood count, liver function and CA19-9 in the non-jaundice group was significantly lower (P < .001). The non-jaundice group had larger tumor size (P = .001), more duodenal carcinoma and pancreatic carcinoma (P < .001), lower resection rate (P = .001) and less pancreatic and perineural invasion (P = .017, P = .002). The I stage was significantly more common in the non-jaundice group (P < .001). The cumulative 5-year survival of the non-jaundice group was significantly higher (P = .032). Multivariate analysis for all patients demonstrated that CEA level, cell differentiation, chemotherapy, and recurrence were independent prognostic factors.Patients with PACs in a non-jaundice stage at diagnosis showed more favorable clinicopathological features and long-term survival than such patients with jaundice.


Assuntos
Neoplasias dos Ductos Biliares/patologia , Colangiocarcinoma/patologia , Neoplasias Duodenais/patologia , Neoplasias Pancreáticas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias dos Ductos Biliares/metabolismo , Bilirrubina/sangue , Colangiocarcinoma/metabolismo , Neoplasias Duodenais/metabolismo , Feminino , Humanos , Icterícia/sangue , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/metabolismo , Estudos Retrospectivos , Análise de Sobrevida , Carga Tumoral , Adulto Jovem
9.
Nano Lett ; 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31774999

RESUMO

NiFe layered double hydroxide (LDH) is thought as a promising bifunctional water splitting catalyst owing to its excellent performances for alkaline oxygen evolution reaction (OER). However, it shows extremely poor activity toward hydrogen evolution reaction (HER) due to the weak hydrogen adsorption. We demonstrated that the integration of Rh species and NiFe-LDH can dramatically improve its HER kinetics without sacrificing the OER performance. The Rh species were initially integrated into NiFe-LDH as oxidized dopants and metallic clusters. In 1M KOH electrolyte, an overpotential of 58 mV is needed to catalyze 10 mA cm-2 HER current density. Furthermore, this catalyst only requires 1.46 V to drive an electrolyzer at 10 mA cm-2. Strong interaction between metallic Rh clusters and NiFe hydroxide during HER process is revealed. The theoretical calculation shows the Rh ions replace Fe ions as the major active sites that are responsible for OER.

10.
Nat Neurosci ; 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31570863

RESUMO

It was recently reported that a magnetic actuator, Magneto, can control neuronal firings at magnetic strength as low as 50 mT (ref. 1), offering an exciting non-invasive approach to manipulating neuronal activity in a variety of research and clinical applications. We investigated whether Magneto can be used to manipulate electric properties of Purkinje cells in the cerebellum, which play critical roles in motor learning and emotional behaviors2. Surprisingly, we found that the application of a magnetic field did not change any electrical properties of Purkinje cells expressing Magneto, raising serious doubt about the previous claim that Magneto can readily be used as a magnetic actuator1.

11.
Neurotherapeutics ; 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31617070

RESUMO

Antimicrotubulin chemotherapeutic agents, including plant-derived vincaalkaloids such as vincristine, can cause peripheral neuropathic pain. Exogenously activated heme oxygenase 1 (HO-1) is a potential therapy for chemotherapy-induced neuroinflammation. In this study, we investigated a role for Nrf2/HO-1/CO in mediating vincristine-induced neuroinflammation by inhibiting connexin 43 (Cx43) production in the spinal cord following the intrathecal application of the HO-1 inducer protoporphyrin IX cobalt chloride (CoPP) or inhibitor protoporphyrin IX zinc (ZnPP), and we analyzed the underlying mechanisms by which levo-corydalmine (l-CDL, a tetrahydroprotoberberine) attenuates vincristine-induced pain. Treatment with levo-corydalmine or oxycodone hydrochloride (a semisynthetic opioid analgesic, used as a positive control) attenuated vincristine-induced persistent pain hypersensitivity and degeneration of the sciatic nerve. In addition, the increased prevalence of atypical mitochondria induced by vincristine was ameliorated by l-CDL in both A-fibers and C-fibers. Next, we evaluated whether nuclear factor E2-related factor 2 (Nrf2), an upstream activator of HO-1, directly bound to the HO-1 promoter sequence and degraded heme to produce carbon monoxide (CO) following stimulation with vincristine. Notably, l-CDL dose-dependently increased HO-1/CO expression by activating Nrf2 to inhibit Cx43 expression in both the spinal cord and in cultured astrocytes stimulated with TNF-α, corresponding to decreased Cx43-mediated hemichannel. Furthermore, l-CDL had no effect on Cx43 following the silencing of the HO-1 gene. Taken together, our findings reveal a novel mechanism by which Nrf2/HO-1/CO mediates Cx43 expression in vincristine-induced neuropathic pain. In addition, the present findings suggest that l-CDL likely protects against nerve damage and attenuates vincristine-induced neuroinflammation by upregulating Nrf2/HO-1/CO to inhibit Cx43 expression.

12.
Int J Med Sci ; 16(9): 1271-1282, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31588193

RESUMO

Nanosecond pulsed electric fields (nsPEFs) is emerged as a potential curative modality to ablate hepatocellular carcinoma (HCC). The application of local ablation is usually limited by insufficiency of liver function. While baicalin, a flavonoid isolated from Scutellaria baicalensis Georgi, has been proven to possess both anti-tumor and protective effects. Our study aimed to estimate different responses of hepatic cancer cells and hepatocytes to the combination of nsPEFs and baicalin. Cell viability, apoptosis and necrosis, mitochondrial transmembrane potential (MTP) and reactive oxygen species (ROS) were examined by CCK-8, FCM, JC-1 and fluorescent probe, respectively. After treatment by nsPEFs, most hepatocytes died by apoptosis, nevertheless, nearly all cancer cells were killed through necrosis. Low concentration of baicalin synergically enhanced nsPEFs-induced suppression and necrosis of HCC cells, nevertheless, the application of baicalin protected normal hepatocytes from the injury caused by nsPEFs, owing to elevating mitochondrial transmembrane potential and reducing ROS generation. Our work provided an advantageous therapy for HCC through the enhanced combination treatment of nsPEFs and baicalin, with which could improve the tumor-ablation effect and alleviate the injury of hepatic tissues simultaneously.

13.
Mol Med Rep ; 20(6): 4973-4983, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31638206

RESUMO

Research has revealed that microRNA (miR)­4500 is downregulated in non­small cell lung cancer (NSCLC), and miR­4500 suppresses tumor growth by targeting lin­28 homolog B and NRAS proto­oncogene, GTPase. In the present study, it was reported that signal transducer and activator of transcription 3 (STAT3) may function as a novel target gene for miR­4500 in NSCLC. The experiments conducted in the present study confirmed that the miR­4500 expression was decreased in NSCLC tissues and cells compared with adjacent normal tissues and a normal lung cell line. miR­4500 suppressed the cell proliferation, migration, invasion and promoted apoptosis of the human NSCLC cell lines A549 and H1975. Expression of STAT3 was negatively correlated with miR­4500 expression in vivo. A luciferase reporter assay suggested that miR­4500 directly targeted the 3' untranslated region of STAT3. The tumor inhibition effect of small interfering RNA STAT3 in A549 and H1975 lines may be partially impaired by a miR­4500 inhibitor. The results of the present study suggests that miR­4500 may be a tumor suppressor and a potential therapeutic target in NSCLC.

14.
Sci Data ; 6(1): 217, 2019 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-31641161

RESUMO

Tree peony (Paeonia suffruticosa Andrew) is a popular ornamental plant due to its large, fragrant and colorful flowers. The floral development is the most important event in its lifecycle. To explore the mechanism that regulate flower development, we sequenced the flower bud transcriptomes of 'High Noon', a reblooming cultivar of P. suffruticosa × P. lutea, using both full-length isoform-sequencing (ISO-seq) and RNA-seq were sequenced. A total of 15.94 Gb raw data were generated in full-length transcriptome sequencing of the 3 floral developmental stages, resulting 0.11 M protein-coding transcripts. Over 457.0 million reads were obtained by RNA-seq in the 3 floral buds. Here, we openly released the full-length transcriptome database of 'High Noon' and RNA-seq database of floral development. These databases can provide a fundamental genetic information of tree peony to investigate its transcript structure, variants and evolution. Data will facilitate to deep analyses of the transcriptome for flower development.

15.
Langmuir ; 35(45): 14486-14491, 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31614089

RESUMO

In this work, a silica nanochannel membrane (SNM) consisting of a high density of vertically aligned channels on an indium tin oxide (ITO) electrode surface was used as a stencil to confine the grafting of ferrocene (Fc) via electrochemical reduction of diazonium cations. The grafting selectively occurs on the underlying ITO surface (namely, the bottom of silica nanochannels) instead of on the nanochannel walls. Thus, the obtained electrode, designated as Fc@SNM/ITO, is composed of an array of silica nanochannels with redox activity on the bottom. Immobilized Fc molecules are able to rectify the electron transfer between the underlying ITO electrode and soluble redox species. In other words, they can promote the electron transfer in one direction while suppressing that in the opposite direction. Anodic and cathodic redox rectification was observed for Fe(CN)64- and IrCl62-, respectively, with the magnitude of current rectification directly proportional to the concentration of redox species. Moreover, because of strong permselectivity of silica nanochannels arising from their ultrasmall size (2-3 nm in diameter) and negatively charged surface (due to deprotonation of surface silanol groups), the access of Fe(CN)64- and IrCl62- to nanochannels strongly depends on the ionic strength of electrolyte solution. A higher ionic strength favors the access of anionic redox species, thus leading to a larger redox current rectification. The redox current rectification phenomenon not only proves the permselective nature of silica nanochannels but also holds potential for the development of electrochemical current rectification-based sensors.

16.
J Nat Prod ; 82(9): 2419-2429, 2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-31503490

RESUMO

Eight new limonoids, toononoids A-H (1-8), eight new B-seco-29-norlimonoids, toonanoronoids A-H (9-16), and seven known analogues were obtained from the EtOAc extract of the twigs and leaves of Toona ciliata. Compounds 2, 4, 8, and 16 are rare lactam-bearing limonoids. Compounds 1, 14, and 15 possess an unusual γ-methoxybutenolide moiety at C-17, while compounds 9, 10, and 15 have a rare 3ß-hydroxy group. Their 2D structure and relative configurations were identified using spectroscopic data. The absolute configurations of 1, 9, 14, and 15 were established via X-ray diffraction crystallography or comparison of experimental and calculated ECD data. The cytotoxicity of the compounds was assessed toward five human tumor cell lines, and their anti-inflammatory activity was assessed based on NO production using LPS-stimulated RAW264.7 macrophages. Compounds 11 and 12 exerted inhibition toward two tumor cell lines (MCF-7, SW-480) with IC50 values between 2.1 and 3.7 µM, while 18-22 inhibited the proliferation of HL-60, MCF-7, and SW-480 cells (IC50 0.6-4.0 µM). Only compound 4 exhibited weak anti-inflammatory activity with an IC50 value of 28.3 µM.

17.
Chem Biol Drug Des ; 2019 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-31562690

RESUMO

Previous studies have reported that genome-wide DNA methylation and differentially expressed genes and proteins are closely associated with drug resistance in Mycobacterium tuberculosis (M. tuberculosis). However, no reports have explored such associations in para-aminosalicylic acid (PAS)-resistant M. tuberculosis H37Rv. Here, we investigated genome-wide methylation and transcriptome and proteome changes to explore the associations between specific genes and PAS resistance in M. tuberculosis H37Rv. The results revealed that 1,388 differentially methylated (1,161 hypermethylated and 227 hypomethylated) genes, 214 significantly differentially expressed (103 up- and 111 down-regulated) genes and 137 differentially expressed (48 up- and 89 down-regulated) proteins were regulated by PAS in M. tuberculosis H37Rv. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that metabolic pathways and ABC transporters were closely associated with differentially methylated and expressed genes, respectively. In addition, correlation analysis revealed that differentially methylated genes were negatively correlated with their transcriptional levels in PAS-resistant M. tuberculosis H37Rv. Furthermore, the existence of five hypermethylated candidate genes (esxC, fabG3, fbpB, papA1 and pks2) in PAS-resistant M. tuberculosis H37Rv was verified using protein-protein interaction analysis in the STRING database. The integrated DNA methylation and transcriptome and proteome analysis could provide valuable resources for epigenetics studies in PAS-resistant M. tuberculosis H37Rv.

18.
Brain Res Bull ; 153: 162-170, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31472184

RESUMO

(3ß,5α,16α,20S)-4,4,14-trimethyl-3,20-bis(methylamino)-9,19-cyclopregnan-16-ol-dihydrochloride (JLX-001), a structural analogue of cyclovirobuxine D (CVB-D), is a novel compound from synthesis. This study aims to confirm the therapeutic effects of JLX001 on ischemic stroke (IS) and research its induction of autophagy function via 5'-AMP-activated protein kinase (AMPK)-Human Serine/threonine-protein kinase (ULK1) signaling pathway activation. The therapeutic effects of JLX001 were evaluated by infarct sizes, brain edema, neurological scores and proportion of apoptotic neurons in Sprague-Dawley (SD) rats with middle cerebral artery occlusion/reperfusion (MCAO/R). The number of autophagosomes was obtained by transmission electron microscopy. The expression of LC3-II was measured by immunofluorescence. p-AMPK and activated ULK1 were detected by western blots. Results showed that JLX001 treatment markedly alleviated cerebral infarcts, edema, neurological scores and proportion of apoptotic neurons in MCAO/R rats. The number of autophagosomes was increased, accompanying with the increased expressions of LC3-II, p-AMPK and ULK1. In summary, JLX001 attenuates cerebral ischemia injury and the underlying mechanisms may relate to inducing autophagy via AMPK-ULK1 signaling pathway activation.

19.
Neuroscience ; 418: 189-204, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31487541

RESUMO

JLX001, a novel compound with similar structure with cyclovirobuxine D (CVB-D), has been proved to exert therapeutical effects on permanent focal cerebral ischemia. However, the protective effects of JLX001 on cerebral ischemia/reperfusion (I/R) injury and its anti-apoptotic effects have not been reported. We investigated the efficacy of JLX001 in two pharmacodynamic tests (pre-treatment test and post-treatment) with rats subjected to middle cerebral artery occlusion/reperfusion (MCAO/R). The pharmacodynamic tests demonstrated that JLX001 ameliorated I/R injury by reducing infarct sizes and brain edema. The results of Morris water maze, neurological scores, cylinder test and posture reflex test implied that JLX001 improved the learning, memory and motor ability after MCAO/R in the long term. Anti-apoptotic effects of JLX001 and its regulation of cytosolic c-Jun N-terminal Kinases (JNKs) signal pathway were confirmed in vivo by co-immunofluorescence staining and western immunoblotting. Furthermore, primary cortical neuron cultures were prepared and exposed to oxygen glucose deprivation/reoxygenation (OGD/R) for in vitro studies. Cytotoxicity test and mitochondrial membrane potential (MMP) test showed that JLX001 enhanced cell survival rate and maintained MMP. Flow cytometry and TdT-mediated dUTP-X nick end labeling (TUNEL) staining demonstrated the anti-apoptotic effects of JLX001 in vitro. Likewise, JLX001 regulated JNK signal pathway in vivo, which was also confirmed by western immunoblotting. Collectively, this study presents the first evidence that JLX001 exerted protective effects against I/R injury by reducing neuronal apoptosis via down-regulating JNK signaling pathway.

20.
Phytochemistry ; 168: 112109, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31494344

RESUMO

Eight undescribed ergostane-type steroids, (22E,24R)-ergosta-7,22-dien-3ß,5α-diol- 6,5-olide, (22E,24R)-ergosta-7,9(11),22-trien-3ß,5ß,6ß-triol, (22E,24R)-6ß-methoxy ergosta-7,9(11),22-trien-3ß,5α,14ß-triol, (22E,24R)-9α,15α-dihydroxyergosta-4,6,8 (14),22-tetraen-3-one, (22E,24R)-ergosta-5,8,22-trien-3ß,11α-dihydroxyl-7-one, (22E,24R)-ergosta-4,7,22-trien-3ß,9α,14ß-trihydroxyl-6-one, (22E,24R)-ergosta-7,22- dien-3ß,9α,14ß-trihydroxyl-6-one, and (22E,24R)-6ß-methoxyergosta-7,22-dien-3ß, 5α,9α,14ß-tetraol, and twenty-one known analogues were isolated from the fruiting bodies of Ganoderma resinaceum Boud. Their chemical structures were determined on the basis of comprehensive spectroscopic analysis and X-ray crystal diffraction, as well as empirical pyridine-induced deshielding effects. Furthermore, selected compounds were evaluated for their inhibitory effects on macrophage activation using an inhibition of nitric oxide production assay. Finally, (22E,24R)-ergosta-5,8,22- trien-3ß,11α-dihydroxyl-7-one, (22E,24R)-ergosta-4,7,22-trien-3ß,9α,14ß-tri hydroxyl-6-one, (22E,24R)-6ß-methoxyergosta-7,22-dien-3ß,5α,9α,14ß-tetraol, (22E,24R)-ergosta-6,9,22-trien-3ß,5α,8α-triol,ergost-6,22-dien-3ß,5α,8α-triol, 5α,6α-epoxy-(22E,24R)-ergosta-8,22-diene-3ß,7α-diol, 5α,6α-epoxy-(22E,24R)- ergosta-8(14),22-diene-3ß,7α-diol, 5α,6α-epoxy-(22E,24R)-ergosta-8(14),22-diene-3ß, 7ß-diol, and 22E-7α-methoxy-5α,6α-epoxyergosta-8(14),22-dien-3ß-ol showed inhibitory effects on NO production with IC50 values ranging from 3.24 ±â€¯0.02 to 35.19 ±â€¯0.41 µM compared with L-NMMA (IC50 49.86 ±â€¯2.13 µM), indicating that they have potential anti-inflammatory activity.

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