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1.
Cancer Med ; 2021 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-33939281

RESUMO

BACKGROUND: To compare the efficacy of first-line bevacizumab plus chemotherapy with cetuximab plus chemotherapy based on the stratification of metastatic colorectal cancer (mCRC) patients with mucinous adenocarcinoma (MA) or mucinous component (MC). METHODS: A retrospective study involving all mCRC patients receiving first-line bevacizumab-based or cetuximab-based chemotherapy at our hospital from September 2013 to January 2020 was conducted. Overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) were compared between the cetuximab-chemotherapy group and the bevacizumab-chemotherapy group on the basis of the conventional pathological classification of MA or MC. RESULTS: A total of 620 patients with mCRC were included in our study, consisting of 141 (22.7%) patients with MA/MC and 479 (77.3%) patients with non-mucinous adenocarcinoma (NMA). In the MA/MC cohort, patients who were treated with bevacizumab-based chemotherapy were associated with significantly better OS than those treated with cetuximab-base chemotherapy (30.0 vs. 26.3 months, p = 0.002), irrespective of tumor sites. The efficacy of bevacizumab-based chemotherapy was higher in nearly all subgroups as shown in the subgroup analysis. In the NMA cohort, median OS was better in the cetuximab plus chemotherapy group than that in the bevacizumab plus chemotherapy group (32.2 vs. 27.0 months, p = 0.005) for left-side mCRC patients, whereas OS was significantly longer in the bevacizumab plus chemotherapy group for right-side mCRC patients (26.0 vs. 20.9 months, p = 0.013). CONCLUSION: Conventional pathological classification (e.g. MA/MC) should be considered when tailoring the individualized optimal treatment for mCRC. Bevacizumab plus chemotherapy as first-line therapy may be the optimal option for patients with MA/MC.

2.
Medicine (Baltimore) ; 100(14): e25208, 2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33832081

RESUMO

ABSTRACT: Morphine dependence (MD) is a very common complication because of the chronic morphine consumption. Studies suggest that repetitive transcranial magnetic stimulation (rTMS) can be used for the treatment of MD. However, there is still lacking evidence to support rTMS for MD. Thus, this retrospective study aimed to investigate the effectiveness and safety of rTMS for patients with MD.In this retrosepctive study, a total of 100 patients with MD were included, and they were divided into a rTMS group (n = 50), and a control group (n = 50). All patients in both groups received occupational therapy. In addition, patients in the rTMS group received rTMS. All patients in both groups received a total of 8 weeks treatment. The outcomes comprised of morphine craving intensity, depression, anxiety, and sleep quality, which were appraised by Visual Analogue Scale (VAS), Self-Rating Depression Scale (SDS), Self-Rating Anxiety Scale (SAS), and Pittsburgh Sleep Quality Index (PSQI), respectively. In addition, treatment-related adverse events were also considered for assessment.After 8 weeks treatment, patients in the rTMS group exerted better benefits in improving VAS (P < .01), SDS (P < .01), SAS (P < .01), and PSQI (P < .01), than patients in the control group. In addition, this study did not identify treatment-related adverse events in both groups.The findings of this study showed that rTMS treatment showed promising effectiveness on patients with MD. However, future studies should focus on warranting the present findings.


Assuntos
Dependência de Morfina/terapia , Estimulação Magnética Transcraniana/métodos , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Terapia Ocupacional , Estudos Retrospectivos
3.
Oncologist ; 2021 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-33830591

RESUMO

LESSONS LEARNED: Bevacizumab combined with S-1 and raltitrexed demonstrated positive antitumor efficacy and acceptable toxicity. This combination might represent a treatment option for refractory metastatic colorectal cancer. BACKGROUND: In patients with metastatic colorectal cancer (mCRC) refractory to standard therapies, S-1 plus raltitrexed showed a good objective response rate (ORR) and significant survival benefit in our previous study. In the present study, we assessed the activity and safety of bevacizumab combined with S-1 and raltitrexed. METHODS: This investigator-initiated, open-label, single-arm, phase II trial was performed at West China Hospital in China. Patients with mCRC who had disease progression after fluoropyrimidine, irinotecan, and oxaliplatin and had at least one measurable lesion were eligible for this trial. Anti-epidermal growth factor receptor (EGFR) (for tumors with wild-type RAS) and anti-vascular endothelial growth factor (VEGF) therapy in the first or second line was allowed, but patients who had been treated with bevacizumab across two consecutive chemotherapy regimens were excluded. Patients received bevacizumab (7.5 mg/kg on day 1), oral S-1 (80-120 mg per day for 14 days), and raltitrexed (3 mg/m2 on day 1) every 3 weeks. The primary endpoint was ORR. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and toxicity. RESULTS: From September 2015 to November 2019, 44 patients were enrolled. Tumor response evaluation was available in 44 patients at the time of the analysis. There were no complete responses; the ORR was 15.9%, and the disease control rate was 54.5%. Median PFS and OS were 110 days (95% confidence interval [CI], 65.0-155.0) and 367 days (95% CI, 310.4-423.6), respectively. The combination was well tolerated. CONCLUSION: Bevacizumab combined with S-1 and raltitrexed showed promising antitumor activity and safety in refractory mCRC.

4.
J Transl Med ; 19(1): 150, 2021 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-33858440

RESUMO

BACKGROUND: Sidedness (right/left) of colorectal cancer (CRC) is essential for treatment. Whether carcinogenesis of tobacco varies by sidedness remains unclear. The present study aims to evaluate the sidedness tendency of cigarette smoking and to explore its impact on prognosis. METHODS: In the multi-center retrospective study, data on 46 166 Chinese CRC patients were extracted from a big-data platform. Logistic regression analyses were performed to evaluate qualitative and quantitative associations between smoking and tumor sidedness. Survival analyses were conducted in metastatic CRC. RESULTS: History of smoking was associated with left-sided CRC (LSCRC; Adjusted odds ratio, 1.25; 95% CI, 1.16 - 1.34; P < .001). The sidedness tendency towards LSCRC increased from non-smokers, to ex-smokers, and to current smokers (P for trend < .001). Longer duration (P for trend < .001) and larger total amount of cigarette smoking (P for trend < .001) were more associated with LSCRC, respectively. The association was confirmed in both left-sided colon cancer and rectal cancer, but was stronger for rectal cancer (P = .016). Alcoholism significantly enhanced the association by 7% (P = .027). Furthermore, prognostic advantage of metastatic LSCRC diminished among ever-smokers, with contrary survival impacts of smoking on either side of CRC. CONCLUSIONS: History of smoking was associated with LSCRC in a positive dose-response relationship, and presented opposite prognostic impacts on right- and left-sided tumors. Smoking potentially plays an instrumental role in the mechanism for sidedness heterogeneity in CRC.

5.
Bioorg Chem ; 111: 104874, 2021 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-33887585

RESUMO

Seven previously undescribed trichothecenes, named trichothecrotocins M-S (1-7), along with five known compounds, were isolated from rice cultures of the potato-associated fungus Trichothecium crotocinigenum. Their structures and absolute configurations were determined through spectroscopic methods, single-crystal X-ray diffraction, and quantum chemistry calculations on ECD. Compound 1 possesses a rare 6,11-epoxy moiety in the trichothecene family. Compound 6 exhibited strong cytotoxic activity against MCF-7 cancer cell lines with an IC50 value of 2.34 ± 0.45 µM. It promoted apoptosis induction in MCF-7 cells. Moreover, cell cycle analysis showed cell cycle arrest caused by compound 6 at the G2/M phase which resulted to cell proliferation inhibition and pro-apoptotic activity. Further quantitative real-time PCR (qRT-PCR) analysis confirmed that the G2/M arrest was accompanied by upregulation of p21 and down regulation of cyclins B1 in 6-treated MCF-7 cells.

6.
Eur J Surg Oncol ; 2021 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-33849741

RESUMO

PURPOSE: This aim of this study was to provide a comprehensive understanding of the clinical characteristics, treatment, and prognosis of patients with small bowel adenocarcinoma (SBA), mucinous small bowel adenocarcinoma (MSBA), and signet ring cell carcinoma of the small bowel (SRCSB). METHODS: Information on patients with SBA, MSBA, and SRCSB (2004-2015) was obtained from the Surveillance, Epidemiology and End Results (SEER) database. Cox proportional hazards models and Kaplan-Meier curves were used for the survival analyses. Propensity-score matching (PSM) was implemented to determine the differences among these tumors. RESULTS: In all, 3697 patients with SBA (n = 3196), MSBA (n = 325) and SRCSB (n = 176) were ultimately eligible for this study. Poor differentiation, local invasion, and lymph node metastasis were more likely to be observed in SRCSB than in SBA and MSBA. Surgery was the most common treatment modality in all groups. The prognosis of SBA was similar to that of MSBA, but better than that of SRCSB in both unmatched and matched cohorts. M stage, surgery, and chemotherapy were identified as independent predictors of survival in all patients. Surgery and chemotherapy could significantly improve outcomes in all groups before and after PSM. Radiotherapy was associated with a survival benefit in patients with SBA, but this trend was not maintained after PSM. Survival advantages of SBA and MSBA were remarkable in the stratified analysis of surgery after PSM. CONCLUSION: Patients with SRCSB had the worst prognosis among all histological types examined. However, surgery and chemotherapy could improve patients survival, regardless of histological type.

7.
Nitric Oxide ; 111-112: 14-30, 2021 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-33839259

RESUMO

Hydrogen sulfide (H2S) is an important gaseous signal molecule which participates in various abiotic stress responses. However, the underlying mechanism of H2S associated salt tolerance remains elusive. In this study, sodium hydrosulfide (NaHS, donor of H2S) was used to investigate the protective role of H2S against salt stress at the biochemical and proteomic levels. Antioxidant activity and differentially expressed proteins (DEPs) of rice seedlings treated by NaCl or/and exogenous H2S were investigated by the methods of biochemical approaches and comparative proteomic analysis. The protein-protein interaction (PPI) analysis was used for understanding the interaction networks of stress responsive proteins. In addition, relative mRNA levels of eight selected identified DEPs were analyzed by quantitative real-time PCR. The result showed that H2S alleviated oxidative damage caused by salt stress in rice seedling. The activities of some antioxidant enzymes and glutathione metabolism were mediated by H2S under salt stress. Proteomics analyses demonstrated that NaHS regulated antioxidant related proteins abundances and affected related enzyme activities under salt stress. Proteins related to light reaction system (PsbQ domain protein, plastocyanin oxidoreductase iron-sulfur protein), Calvin cycle (phosphoglycerate kinase, sedoheptulose-1,7-bisphosphatase precursor, ribulose-1,5-bisphosphate carboxylase/oxygenase) and chlorophyll biosynthesis (glutamate-1-semialdehyde 2,1-aminomutase, coproporphyrinogen III oxidase) are important for NaHS against salt stress. ATP synthesis related proteins, malate dehydrogenase and 2, 3-bisphosphoglycerate-independent phosphoglycerate mutase were up-regulated by NaHS under salt stress. Protein metabolism related proteins and cell structure related proteins were recovered or up-regulated by NaHS under salt stress. The PPI analysis further unraveled a complicated regulation network among above biological processes to enhance the tolerance of rice seedling to salt stress under H2S treatment. Overall, our results demonstrated that H2S takes protective roles in salt tolerance by mitigating oxidative stress, recovering photosynthetic capacity, improving primary and energy metabolism, strengthening protein metabolism and consolidating cell structure in rice seedlings.

8.
Regul Toxicol Pharmacol ; 123: 104921, 2021 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-33894279

RESUMO

OBJECTIVE: The study was primarily used to evaluate subchronic oral toxicity of rhubarb extract. METHODS: The rhubarb extract was orally administered to rats at doses of 0.00, 0.65, 1.62 and 4.05 g/kg BW/day for 13 weeks with a recovery period of 4 weeks. The weight and the relative organ weight of the kidney in the 0.65 g/kg BW group were significantly increased but no significant changes were seen in renal histopathology. When the rats received rhubarb extract at 1.62 g/kg BW or above, the relative weight of the spleen and kidney were significantly increased; the kidney was also swollen and black with hydronephrosis. Histologic examination showed that there was an obvious increase in pigment deposition in renal tubular epithelial cells. No toxic related changes were observed in the 0.65 g/kg BW group, even though organ weight was increased and relative ratio to body weight of kidney were observed at 0.65 g/kg BW dosage, no significant renal histopathologic changes were detected at this dose. Based on the current study conditions and results, the no observed adverse effect level (NOAEL) of rhubarb extract in rats is 0.65 g/kg BW/day.

9.
Artigo em Inglês | MEDLINE | ID: mdl-33826512

RESUMO

This paper explores the non-convex composition optimization consisting of inner and outer finite-sum functions with a large number of component functions. This problem arises in important applications such as nonlinear embedding and reinforcement learning. Although existing approaches such as stochastic gradient descent (SGD) and stochastic variance reduced gradient (SVRG) descent can be applied to solve this problem, their query complexities tend to be high, especially when the number of inner component functions is large. Therefore, to significantly improve the query complexity of current approaches, we have devised the stochastic composition via variance reduction (SCVR). What's more, we analyze the query complexity under different numbers of inner function and outer function. Based on different kinds of estimation of inner component function, we also present the SCVRII algorithm, though the order of query complexities are the same with SCVR. Additionally, we propose an extension to handle the mini-batch cases, which improve the query complexity under the optimal mini-batch size. The experimental results validate our proposed algorithms and theoretical analyses.

10.
Genes (Basel) ; 12(3)2021 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-33799408

RESUMO

The movement of abnormal vascular smooth muscle cells (VSMCs) contributes to intimal hyperplasia in vein graft disease. Circular RNAs (circRNAs) are single stranded RNAs with 3' and 5' ends covalently joined together. They have been shown to regulate cell function in many diseases. NOVA1 is considered to be a brain-specific splicing factor that plays an important role in the nervous system and cancer. The role of NOVA1 in VSMCs remains unclear. In the present study, transcriptome sequencing was used to identify differentially expressed circRNAs in the rat vein graft model. A novel circRNA, circUVRAG, was decreased in the grafted vein and stably located in the cytoplasm. Knockdown of circUVRAG suppressed VSMC adhesion and migration. In addition, we demonstrated that the alternative splicing factor NOVA1 co-located with UVRAG pre-mRNA in the nucleus and modulated the production of circUVRAG. These new discoveries may serve as a potential means to treat intimal hyperplasia after vein grafts.

11.
Microorganisms ; 9(3)2021 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-33810191

RESUMO

Dimethylsulfoniopropionate (DMSP) is one of Earth's most abundant organosulfur molecules. Recently, many marine heterotrophic bacteria were shown to produce DMSP, but few studies have combined culture-dependent and independent techniques to study their abundance, distribution, diversity and activity in seawater or sediment environments. Here we investigate bacterial DMSP production potential in East China Sea (ECS) samples. Total DMSP (DMSPt) concentration in ECS seawater was highest in surface waters (SW) where phytoplankton were most abundant, and it decreased with depth to near bottom waters. However, the percentage of DMSPt mainly apportioned to bacteria increased from the surface to the near bottom water. The highest DMSP concentration was detected in ECS oxic surface sediment (OSS) where phytoplankton were not abundant. Bacteria with the genetic potential to produce DMSP and relevant biosynthesis gene transcripts were prominent in all ECS seawater and sediment samples. Their abundance also increased with depth and was highest in the OSS samples. Microbial enrichments for DMSP-producing bacteria from sediment and seawater identified many novel taxonomic groups of DMSP-producing bacteria. Different profiles of DMSP-producing bacteria existed between seawater and sediment samples and there are still novel DMSP-producing bacterial groups to be discovered in these environments. This study shows that heterotrophic bacteria significantly contribute to the marine DMSP pool and that their contribution increases with water depth and is highest in seabed surface sediment where DMSP catabolic potential is lowest. Furthermore, distinct bacterial groups likely produce DMSP in seawater and sediment samples, and many novel producing taxa exist, especially in the sediment.

12.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 39(2): 170-174, 2021 Apr 01.
Artigo em Chinês | MEDLINE | ID: mdl-33834671

RESUMO

OBJECTIVES: The present study aimed to explore the innervation of the anterior hard palatine and its relationship with individual development stage. Specifically, the effects of anesthesia on patients of different ages were observed, and neurodevelopment in the maxillofacial region was invesitgated. References that are helpful in selecting local anesthesia were provided. METHODS: A total of 182 patients with mixed dentition were randomly divided into the nasopalatine nerve block and greater palatine nerve block groups. Then, 219 patients with permanent dentition were divided into an adolescent group (13-18 years old) and adult group (over 19 years old), all of whom underwent bilateral greater palatine nerve block. Palatal mucosal pain sensation was tested pre- and post-anesthesia with Von Frey hairs. RESULTS: Among the children with mixed dentition, bilateral greater palatine nerve block tended to result in better anesthetic effects than nasopalatine nerve block (P<0.05), except in the incisive papilla. No difference in anesthetic effect was observed between adolescents and adults (P>0.05). The bilateral greater palatine nerve block was more effective in inducing an anesthestic effect in the anterior hard palatine in mixed dentition than in permanent dentition (over 13 years old; P<0.05). CONCLUSIONS: The sensation of the anterior hard palatine seems mainly dominated by the greater palatine nerve until mixed dentition and gradually shifted to the nasopalatine nerve in conjunction with maxillary development and tooth replacement. Hence, the innervation of the anterior hard palatine induce a secondary development during the development of the maxilla.


Assuntos
Bloqueio Nervoso , Palato Duro , Adolescente , Adulto , Criança , Dentição Mista , Humanos , Maxila , Nervo Maxilar , Palato , Adulto Jovem
13.
Exp Cell Res ; 403(1): 112582, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33812868

RESUMO

The cytoophidium, a subcellular structure composed of CTP synthase, can be observed during the division of Schizosaccharomyces pombe. Cytoophidium formation changes periodically with the cell cycle of yeast cells. Here, we find that histone chaperone Slm9 is required for the integrity of cytoophidia in fission yeast. When the slm9 gene is knocked out, we observe that morphological characteristics, the abundance of cytoophidia and the division of the yeast cells are significantly affected. Fragmented cytoophidia occur in slm9 mutant cells, a phenomenon rarely observed in wild-type cells. Our study reveals a potential link between a chromosomal regulatory factor and cytoophidium biogenesis.

14.
Cell Signal ; 84: 110025, 2021 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-33915247

RESUMO

Recent studies have emphasized microRNAs (miRs) as crucial regulators in the occurrence and development of pancreatic cancer that continues to be one of the deadliest malignancies with few effective therapies. The study aimed to investigate the functional role of miR-873 and its associated mechanism to unravel the biological characteristics of pancreatic cancer stem cells in tumor growth. The expression patterns of pleckstrin-2 (PLEK2) and miR-873 were detected in the pancreatic cancer tissues. Then to further investigate specific role of miR-873, the pancreatic cancer stem cells were treated with miR-873 mimic, PLEK2, small interfering RNA against PLEK2, LY294002 (inhibitor of phosphatidylinositol 3-kinase/protein kinase B [PI3K/AKT] pathway) to detect the relative gene expression as well as their effects on cell self-renewal, proliferation and apoptosis. Finally, the tumor formation in nude mice was measured to verify the preceding results in vivo. Pancreatic cancer tissues exhibited a decline of miR-873 expression and an enhancement of PLEK2 expression. miR-873 targeted PLEK2 and downregulated its expression, leading to inhibition of PI3K/AKT pathway. Overexpressed miR-873 or silenced PLEK2 inhibited the self-renewal and proliferation while promoting the apoptosis of pancreatic cancer stem cells. Tumor formation was inhibited by overexpressed miR-873 or silenced PLEK2 in nude mice. Overall, miR-873 can suppress the self-renewal and proliferation of pancreatic cancer stem cells by blocking PLEK2-dependent PI3K/AKT pathway. Hence, this study contributes to understanding the role of miR-873 in pancreatic cancer stem cells and its underlying molecular mechanisms to aid in the development of effective pancreatic cancer therapeutics.

15.
Cancer Biol Ther ; 22(3): 204-215, 2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33691611

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers in the modern world, in part due to poor delivery of chemotherapeutics. Sonoporation can be used to enhance the efficacy of standard of care therapies for PDAC. Using xenograft models of PDAC we investigate sonoporation using four ifferent ultrasound contrast agents (UCAs) and two ultrasound regimens to identify the ideal parameters to increase therapeutic efficacy. MIA-PaCa2 xenografts in over 175 immunodeficient mice were treated with gemcitabine and paclitaxel and subjected to low or high power ultrasound (60 and 200 mW/cm2 respectively) in conjunction with one of four different UCAs. The UCAs investigated were Definity®, SonoVue®, Optison™ or Sonazoid™. Tumor volumes, vascularity, hemoglobin, and oxygenation were measured and compared to controls. High power treatment in conjunction with Sonazoid sonoporation led to significantly smaller tumors when started early (tumors ~50mm3; p = .0105), while no UCAs significantly increased efficacy in the low power cohort. This trend was also found in larger tumors (~250mm3) where all four UCA agents significantly increased therapeutic efficacy in the high power group (p < .01), while only Definity and SonoVue increased efficacy in the low power cohort (p < .03). Overall, the higher power ultrasound treatment modality was more consistently effective at decreasing tumor volume and increasing vascularity characteristics. In conclusion, Sonazoid was the most consistently effective UCA at decreasing tumor volume and increasing vascularity. Thus, we are pursuing a larger phase II clinical trial to validate the increased efficacy of sonoporation in conjunction with chemotherapy in PDAC patients.

16.
ACS Appl Mater Interfaces ; 13(12): 14365-14376, 2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33736431

RESUMO

An efficient strategy that can guide the synthesis of materials with superior mechanical properties is important for advanced material/device design. Here, we report a feasible way to enhance hardness in transition-metal monocarbides (TMCs) by optimally filling the bonding orbitals of valence electrons. We demonstrate that the intrinsic hardness of the NaCl- and WC-type TMCs maximizes at valence electron concentrations of about 9 and 10.25 electrons per cell, respectively; any deviation from such optimal values will reduce the hardness. Using the spark plasma sintering technique, a number of W1-xRexC (x = 0-0.5) have been successfully synthesized, and powder X-ray diffractions show that they adopt the hexagonal WC-type structure. Subsequent nanoindentation and Vickers hardness measurements corroborate that the newly developed W1-xRexC samples (x = 0.1-0.3) are much harder than their parent phase (i.e., WC), marking them as the hardest TMCs for practical applications. Furthermore, the hardness enhancement can be well rationalized by the balanced occupancy of bonding and antibonding states. Our findings not only elucidate the unique hardening mechanism in a large class of TMCs but also offer a guide for the design of other hard and superhard compounds such as borides and nitrides.

17.
Zhongguo Zhong Yao Za Zhi ; 46(6): 1467-1476, 2021 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-33787145

RESUMO

This study aimed to investigate the effect of serum containing ginseng and Moutan Cortex on human umbilical vein endothelial cells(HUVEC) injured with hydrogen peroxide(H_2O_2). HUVEC injured with H_2O_2 were divided into 6 groups, namely blank group, model group, ginsenoside(TGG) group, total glucosides of Moutan Cortex(TGM) group, paeonol(P) group and TGG+TGM+P group. After 24 hours of co-culture with H_2O_2, the activities of succinate dehydrogenase(SDH) and Ca~(2+)-Mg~(2+)-ATP were detected by microenzyme labeling. The apoptosis rate, intracellular Ca~(2+) concentration, reactive oxygen species(ROS) and mitochondrial membrane potential(JC-1) were detected by flow cytometry. The expressions of mitochondrial apoptosis pathway-related proteins Bax, Bcl-2, cytochrome C, caspase-3 and caspase-9 were detected by Western blot. The results showed that H_2O_2 could significantly damage HUVEC, decrease the activity of SDH and Ca~(2+)-Mg~(2+)-ATP(P<0.01), while could increase the apoptosis+necrosis rate, JC-1 decline rate, ROS increase rate and Ca~(2+) concentration increase rate(P<0.01). Serum containing ginseng and Moutan Cortex could increase the activities of SDH and Ca~(2+)-Mg~(2+)-ATP to different degrees, decrease the apoptosis+necrosis rate, JC-1 decline rate, ROS increase rate and Ca~(2+) concentration increase rate(P<0.05 or P<0.01), and down-regulate the protein expressions of Bax, caspase-3, caspase-9, cytochrome C, and up-regulate the protein expression of Bcl-2. The results showed that serum containing ginseng and Moutan Cortex has a protective effect on vascular endothelial cell injury induced by ROS, and its mechanism may be related to the improvement of mitochondrial function and the inhibition of the activation of mitochondrial apoptosis pathway.


Assuntos
Medicamentos de Ervas Chinesas , Panax , Apoptose , Medicamentos de Ervas Chinesas/farmacologia , Células Endoteliais da Veia Umbilical Humana , Humanos , Paeonia , Espécies Reativas de Oxigênio
18.
Chem Biodivers ; 18(4): e2001012, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33644937

RESUMO

Chemical investigation of the ethanol extract of the branch and leaves of Illicium majus resulted in the isolation of four new phenylpropanoid glycosides (1-4) and one new phenolic glycoside (9), along with 13 known ones. Spectroscopic techniques were used to elucidate the structures of the new isolates such as 3-[(2R,3S)-7-hydroxy-2-(4-hydroxy-3-methoxyphenyl)-3-(hydroxymethyl)-2,3-dihydro-1-benzofuran-5-yl]propyl ß-D-glucopyranoside (1), [(2R,3S)-7-hydroxy-2-(4-hydroxy-3-methoxyphenyl)-5-(3-hydroxypropyl)-2,3-dihydro-1-benzofuran-3-yl]methyl 2-O-α-L-rhamnopyranosyl-ß-D-glucopyranoside (2), [(2R,3S)-7-hydroxy-2-(4-hydroxy-3-methoxyphenyl)-5-(3-hydroxypropyl)-2,3-dihydro-1-benzofuran-3-yl]methyl 2-O-α-L-rhamnopyranosyl-ß-D-xylopyranoside (3), 3-[(2R,3S)-3-({[2-O-(4-O-acetyl-α-L-rhamnopyranosyl)-ß-D-xylopyranosyl]oxy}methyl)-7-hydroxy-2-(4-hydroxy-3-methoxyphenyl)-2,3-dihydro-1-benzofuran-5-yl]propyl acetate (4), and 4-(2-hydroxyethyl)phenyl 3-O-ß-D-glucopyranosyl-ß-D-glucopyranoside (9). Free radical scavenging activities of the isolates were elucidated through the DPPH assay method. The most active compounds, 1-O-caffeoyl-ß-D-glucopyranose (17) and soulieana acid 1 (18), exhibited moderate radical scavenging activities (IC50 =37.7±4.4 µM and IC50 =97.2±3.4 µM, respectively). The antibacterial activities of the isolates against Staphylococcus aureus and Escherichia coli were also assessed, and no activity was shown at the measured concentration (<32 µg/mL).

19.
Phytochemistry ; 186: 112729, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33721798

RESUMO

Five pairs of undescribed naphthalenone derivative enantiomers, xylarinaps A-E, including one pair of indole naphthalenones and four pairs of naphthalene-naphthalenone dimers, were isolated from the ethyl acetate extracts of the solid fermentation of Xylaria nigripes, which has been used as a traditional Chinese medicinal fungus for the treatment of insomnia, trauma, and depression. The structures of these enantiomers were elucidated based on comprehensive spectroscopic analysis, including NMR and HRESIMS. Their absolute configurations were assigned by the experimental and calculated ECD data. The neuroprotective effects of all the compounds against damage to PC12 cells by oxygen and glucose deprivation (OGD) were evaluated by an in vitro bioassay. The results revealed that xylarinaps A, B, D, and E significantly enhanced cell viability, decreased the levels of malondialdehyde (MDA), increased the levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), as well as further markedly inhibiting apoptosis, which indicated that these results could be the mode of action of their neuroprotective effect.


Assuntos
Fármacos Neuroprotetores , Animais , Apoptose , Ascomicetos , Glutationa Peroxidase/metabolismo , Glutationa Peroxidase/farmacologia , Malondialdeído , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo , Células PC12 , Ratos , Superóxido Dismutase/metabolismo
20.
Nat Prod Res ; : 1-7, 2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33715538

RESUMO

Four new resorcinol derivatives, namely (-)/(+)-xylarinig A (1), as well as xylarinigs B (2) and C (3), were isolated from the ethyl acetate extracts of the solid fermentation of Xylaria nigripes. Their structures were established by comprehensive spectroscopic analysis combined with electronic circular dichroism (ECD) calculations. Compound 1 is an optical mixture, and was resoluted into optical pure enatiomers (+)-1 and (-)-1 by chiral HPLC. The neuroprotective effects of 1-3 against the damage of PC12 cells induced by oxygen and glucose deprivation (OGD) were evaluated.

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