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1.
Bioorg Med Chem Lett ; : 127719, 2020 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-33253878

RESUMO

The extraction, purification, structure and hepatoprotective activity of a homogenous polysaccharide (SPS60) from Sabia parviflora were investigated. SPS60 was screened after purification with Sephadex G-100 and showed the excellent hepatoprotective activity. Its structural characteristics were investigated by Time of flight mass spectrometry (TOF-MS), PMP Pre-column derivatization-HPLC (PMP-HPLC), nuclear magnetic resonance (NMR) spectroscopy and Atomic Force Microscopy (AFM). The results showed that SPS60 possessed the molecular weight of 16900 Da and the monosaccharide component was glucose, as well as a 1 → 6 glycosidic bond. The results of atomic force microscopy (AFM) show that SPS60 is a blocky sphere in solution. Furthermore, the SPS60 could significantly improve the survival rate of LO2 hepatocytes which were damaged by CCl4. Therefore, SPS60 may be an active substance of S. parviflora as a local functional tea.

2.
Poult Sci ; 99(11): 6173-6187, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33142535

RESUMO

This study investigated the factors that caused the differences in egg production during the development of ovarian follicles in Leizhou black ducks. Leizhou black ducks population was divided into 2 groups as high-yield group (HG) and low-yield group (LG). The number of eggs (NE), age at first egg (AFE), weight at first egg, and egg weight (EW) of both groups were recorded, and differences were analyzed using the t test. The logistic model was used to simulate the egg production curves to analyze the production rules. The ovarian follicles of both duck groups were collected to count the number of different grades sized follicles, weigh the ovaries, and observe follicular sections to analyze the developmental differences. Ovarian transcriptomic sequencing was performed to investigate differentially expressed genes and signal pathways in both duck groups. The results revealed a significant difference (P < 0.01) in the NE laid, AFE, and EW between both groups. Comparatively, HG had significantly more (P < 0.01) large yellow follicles (LYF) than LG. The density of medullary layer cells of the follicle section was greater in HG than LG ducks. Transcriptome sequencing revealed a total of 1,027 differentially expressed genes between the HG and LG ducks of which 495 genes were upregulated, and 532 genes were downregulated. Fifty genes were related to reproduction and reproductive processes. Kyoto Encyclopedia of Genes and Genomes-enriched signaling pathways revealed 274 signal pathways enriched in these differentially expressed genes of which the steroid biosynthesis pathway was significantly enriched. Analysis (Q < 0.05) showed that HSD3ß â†’ gonadotropin-releasing hormone (GnRH) and estrogen receptor (ESR) → LHß/ERK1/2 were enriched in the steroid biosynthesis signal pathway. Follicle-stimulating hormone signal pathway mediated by HSD3ß â†’ GnRH and ESR → LHß/ERK1/2 may be involved in ovarian follicle development to regulate LYF reserve process and affect its ovulation cycle, which in turn influence the egg production of Leizhou black ducks.

3.
J Exp Clin Cancer Res ; 39(1): 243, 2020 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-33187536

RESUMO

BACKGROUND: Radiotherapy is regarded as a milestone for the cure of cervical cancer. However, clinical outcome heavily be hindered by radioresistance. So, exploring the underlying mechanism of radioresistance, and find potential target, well deserve fully emphasis. METHODS: In this study, we developed two novel radiation resistance cervical cancer cell lines, which could mimic clinical radioresistance. In order to find new potential targets, RNA-Seq, database analysis, streptavidin-agarose and LC/MS were used. Pull-down, luciferase and rescue assays were conducted to explore the regulatory mechanisms. To further evaluate the correlation between therapeutic responses and HMGB3/hTERT expression, 172 cervical cancer patients were recruited. RESULTS: Knockdown of HMGB3 significantly inhibit the DNA damage repair and induced more γH2AX foci, leading to enhanced chemo- and radio-sensitivity in vitro and in vivo, whereas HMGB3 overexpression has the opposite effects. HMGB3 promotes cell growth and radioresistance by transcriptionally up-regulating hTERT via the specifical binding of HMGB3 at the hTERT promoter region from - 902 to - 321. HMGB3 knockdown-mediated radiosensitization could be reversed by the overexpressed hTERT in both cervical cancer cell lines and xenograft tumor mouse model. Furthermore, clinical data from 172 cervical cancer patients proved that there was a positive correlation between HMGB3 and hTERT expression, and high expression of HMGB3/hTERT predicted poor response to radiotherapy, worse TNM stages and shorter survival time. CONCLUSION: Here, we have identified HMGB3/hTERT signaling axis as a new target for cervical cancer radioresistance. Our results provide new insights into the mechanism of cervical cancer radioresistance and indicate that targeting the HMGB3/hTERT signaling axis may benefit cervical cancer patients.

4.
Cell Death Differ ; 2020 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-33162555

RESUMO

CRSP8 plays an important role in recruiting mediators to genes through direct interaction with various DNA-bound transactivators. In this study, we uncovered the unique function of CRSP8 in suppressing thyroid cancer differentiation and promoting thyroid cancer progression via targeting IKKα signaling. CRSP8 was highly expressed in human thyroid cancer cells and tissues, especially in anaplastic thyroid cancer (ATC). Knockdown of CRSP8 suppressed cell growth, migration, invasion, stemness, and induced apoptosis and differentiation in ATC cells, while its overexpression displayed opposite effects in differentiated thyroid cancer (DTC) cells. Mechanistically, CRSP8 downregulated IKKα expression by binding to the IKKα promoter region (-257 to -143) to negatively regulate its transcription. Knockdown or overexpression of IKKα significantly reversed the expression changes of the differentiation and EMT-related markers and cell growth changes mediated by CRSP8 knockdown or overexpression in ATC or DTC cells. The in vivo study also validated that CRSP8 knockdown inhibited the growth of thyroid cancer by upregulating IKKα signaling in a mouse model of human ATC. Furthermore, we found that CRSP8 regulated the sensitivity of thyroid cancer cells to chemotherapeutics, including cisplatin and epirubicin. Collectively, our results demonstrated that CRSP8 functioned as a modulator of IKKα signaling and a suppressor of thyroid cancer differentiation, suggesting a potential therapeutic strategy for ATC by targeting CRSP8/IKKα pathway.

5.
J Neurosci Res ; 2020 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-33164225

RESUMO

With global increases in the aging population, the number of patients with dementia is greatly increasing, which has become a big social problem. Many studies have shown strong associations between oral disorders and systemic disorders, such as diabetes, arthritis, sepsis, aspiration pneumonia, arteriosclerosis, bacterial endocarditis, and other cardiovascular diseases. Similarly, numerous cross-sectional studies showed that patients with dementia usually have poor oral conditions and tooth loss. These have long been considered as a result of difficulty with oral care due to impaired cognitive function, memory, and physical ability in patients with dementia. Indeed, even in patients with mild cognitive impairment, oral care becomes insufficient owing to decreases in spontaneity of grooming and finger dexterity. However, recent studies have shown that tooth loss and occlusal dysfunction may affect brain function and trigger the onset of dementia found in neurodegenerative diseases including Alzheimer's disease. In this review, we highlight the relationships among aging, oral dysfunction, and the development of dementia. Increasing evidence suggests that oral dysfunction is not only a result of dementia in the elderly people, but could also be a causative factor for the onset of dementia.

6.
J Biol Chem ; 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33067321

RESUMO

Alzheimer's disease (AD) is characterized by neuronal loss and accumulation of amyloid ß-protein (Aß) in the brain parenchyma. Sleep impairment is associated with AD and affects about 25-40% of patients in the mild-to-moderate stages of the disease. Sleep deprivation leads to increased Aß production; however, its mechanism remains largely unknown. We hypothesized that the increase in core body temperature induced by sleep deprivation may promote Aß production. Here, we report temperature-dependent regulation of Aß production. We found that an increase in temperature, from 37°C to 39°C, significantly increased Aß production in amyloid precursor protein-overexpressing cells. We also found that high temperature (39°C) significantly increased the expression levels of heat shock protein 90 (Hsp90) and the C-terminal fragment of presenilin 1 (PS1-CTF), and promoted γ-secretase complex formation. Interestingly, Hsp90 was associated with the components of the premature γ-secretase complex, anterior pharynx defective-1 (APH-1) and nicastrin (NCT), but was not associated with PS1-CTF or presenilin enhancer-2. Hsp90 knockdown abolished the increased level of Aß production and the increased formation of the γ-secretase complex at high temperature in culture. Furthermore, with in vivo experiments, we observed increases in the levels of Hsp90, PS1-CTF, NCT, and the γ-secretase complex in the cortex of mice housed at higher room temperature (30°C) compared with those housed at standard room temperature (23°C). Our results suggest that high temperature regulates Aß production by modulating γ-secretase complex formation through the binding of Hsp90 to NCT/APH-1.

7.
Transl Oncol ; 14(1): 100876, 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-33007707

RESUMO

BACKGROUND: Epirubicin is a first-line chemotherapeutic drug for the clinical treatment of diffuse large B cell lymphoma (DLBCL), but the overexpression of multidrug resistance (MDR) transporter proteins, especially P-glycoprotein (P-gp), renders epirubicin ineffective. Some studies reveal the potential role of melatonin in chemotherapeutic synergy and MDR. METHODS: The cell viability and apoptosis were determined by CCK-8 assay and acridine orange/ethidium bromide (AO/EB) fluorescence staining assay. Immunofluorescence and immunohistochemical staining were used to detect the expression of P-gp in DLBCL cells and tissues. Rhodamine-123 accumulation assay was used to evaluate the pump function of P-gp. The possible mechanisms of melatonin sensitize DLBCL cells to epirubicin were explored by western blotting, cytochrome C release, and pulldown assay. RESULTS: Melatonin significantly enhanced the epirubicin-induced cell proliferation suppression, epirubicin-induced apoptosis, and reduced the IC50 value of epirubicin. Further, melatonin synergized with epirubicin to promote the activation of the mitochondria-mediated apoptosis pathway and increased the accumulation of epirubicin in DLBCL cells by inhibiting the expression and function of P-gp. Immunohistochemical staining studies revealed that P-gp expression was positively correlated with P65 expression. Epirubicin was subsequently discovered to upregulate the expression of P-gp by activating the NF-κB pathway in the DLBCL cells. Melatonin reduced the amount of P65 protein in the nucleus and abrogated the ability of P65 to bind to the ABCB1 promoter, decisively suppressing P-gp expression. CONCLUSIONS: Our results demonstrated that melatonin inactivates the NF-κB pathway and downregulates the expression of P-gp, ultimately sensitizing DLBCL cells to the epirubicin that suppresses their growth.

8.
Int J Cancer ; 2020 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-33113150

RESUMO

Limited and inefficient treatment options exist for metastatic relapsed cervical cancer (MRCC), and there are currently no reliable indicators to guide therapeutic selection. We performed deep sequencing analyses targeting 322 cancer-related genes in plasma cell-free DNA and matched white blood cells in 173 serial blood samples from 82 locally advanced CC (LACC) or MRCC patients and when possible during treatment. We identified five notable nonsynonymous mutant genes (PIK3CA, BRAF, GNA11, FBXW7 and CDH1) in the MRCC samples as the metastatic relapse significantly mutated (MSG) genes and found that MRCC patients with any detectable MSG mutations had significantly shorter progression-free survival (PFS) (P = .005) and overall survival (OS) (P = .007) times than those without detectable MSG mutations. Additionally, analyses of matched prechemotherapy and postchemotherapy plasma revealed that a reduction in the number of MSG mutations after chemotherapy was significantly associated with partial remission (PR) and stable disease (SD) (P = .007). Among the patients included in the longitudinal tracking ctDNA analysis, an increase in MSG mutations was observed earlier in response to disease progression than radiological imaging. Our results outline the mutation profiles of MRCC. We show how longitudinal monitoring with ctDNA in liquid biopsy samples provides both predictive and prognostic information during treatment.

9.
ChemMedChem ; 2020 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-32935462

RESUMO

Mammalian carboxylesterases (CES) are key enzymes that participate in the hydrolytic metabolism of various endogenous and exogenous substrates. Human carboxylesterase 2A (hCES2A), mainly distributed in the small intestine and colon, plays a significant role in the hydrolysis of many drugs. In this study, 3-arylisoquinolones 3 h [3-(4-(benzyloxy)-3-methoxyphenyl)-7,8-dimethoxyisoquinolin-1(2H)-one] and 4 a [3-(4-(benzyloxy)-3-methoxyphenyl)-4-bromo-7,8-dimethoxyisoquinolin-1(2H)-one] were found to have potent inhibitory effects on hCES2A (IC50 =0.68 µΜ, Ki =0.36 µΜ) and excellent specificity (more than 147.05-fold over hCES1 A). Moreover, 4 a exhibited threefold improved inhibition on intracellular hCES2A in living HepG2 cells relative to 3 h, with an IC50 value of 0.41 µΜ. Results of inhibition kinetics studies and molecular docking simulations demonstrate that both 3 h and 4 a can bind to multiple sites on hCES2A, functioning as mixed inhibitors. Structure-activity relationship analysis revealed that the lactam moiety on the B ring is crucial for specificity towards hCES2A, while a benzyloxy group is optimal for hCES2A inhibitory potency; the introduction of a bromine atom may enhance cell permeability, thereby increasing the intracellular hCES2A inhibitory activity.

10.
J Orthop Surg Res ; 15(1): 386, 2020 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-32894147

RESUMO

BACKGROUND: The Microplasty (MP) instrumentation designed for the Phase III Oxford mobile-bearing unicompartmental knee arthroplasty (UKA) system is considered a better option to achieve more accurate component positioning and alignment. In the present study, we focused on short-term clinical and radiological outcomes to determine whether the MP instrumentation can reduce the short-term revision rate and occurrence of outliers of metallic components. METHODS: The literature in PubMed, Embase, the Cochrane Library, and Web of Science was searched up to May 2020. Studies were scrutinized by two independent authors, and the revision rate, complication spectrum, and radiological assessment with outlier rates were specifically analyzed. RevMan 5.3 was used for the statistical analysis. RESULTS: Seven studies were included in the meta-analysis. Four studies reported both clinical and radiological outcomes, two reported only radiological outcomes, and one reported only clinical outcomes. The pooled analysis showed that the revision rate in the MP instrumentation group was 0.866 per 100 component years, while that in the control group was 1.124 (odds ratio, 0.77; p < 0.05). The subgroup analysis of the bearing dislocation rate showed a significantly greater reduction in the Korean population than in the populations of other countries (p < 0.05). The radiological assessment showed that the alignment of the femoral component was significantly improved (p < 0.05), while that of the tibial component was not (p > 0.05). CONCLUSION: The newly developed MP instrumentation for Oxford UKA significantly reduced the revision rate of this treatment. The positioning of the femoral component was also proven to be better by radiological assessments.

11.
PLoS One ; 15(9): e0239461, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32970740

RESUMO

OBJECTIVE: To examine the association of health insurances on catastrophic health expenditure (CHE), and compares that among different health insurances in the last two decades in China. METHODS: The systematic review was conducted according to the Cochrane Handbook and reported according to PRISMA. We searched English and Chinese literature databases including PubMed, EM base, web of science, CNKI, Wan fang, VIP and CBM (Sino Med) for empirical studies on the association between health insurance and CHE from January 2000 to June 2020. Study selection, data extraction and quality appraisal were conducted by two reviewers. The secular trend of CHE rate and comparisons between population with different health insurances were conducted using meta-analysis, subgroup analysis and meta-regression. RESULTS: A total of 4874 citations were obtained, and finally 30 eligible studies with 633917 participants were included. The overall CHE rate was 13.6% (95% CI: 13.1% - 14.0%) from Jan 2000 to June 2020, 12.8% (95% CI: 12.2% - 13.3%) for people with health insurance compared with 16.2% (95% CI:15.4% - 16.9%) for people without health insurance. For types of insurance, the CHE rate was 13.0% (95% CI: 12.4% - 13.6%) for people with new rural cooperative medical scheme (NCMS), 11.9% (95% CI: 9.3% - 14.5%) for urban employees health insurance (UEBMI), 12.0% (95% CI: 8.3% - 15.6%) for urban residents health insurance (URBMI), and 18.0% (95% CI: - 4.5% - 31.5%) for commercial insurance. However, the CHE rate in China has increased in the past 20 years, even adjusted for other factors. The CHE rate of people with NCMS has increased significantly more than people with UEBMI and URBMI. CONCLUSION: In the past 20 years, the basic health insurance plan has reduce the rate of CHE to a certain extent, but due to the rapid increase in medical costs and the release of health needs in recent years, it masks the role of health insurance. More efforts are needed to control unreasonable medical demand and rising costs.


Assuntos
Gastos em Saúde/tendências , Disparidades em Assistência à Saúde/economia , Seguro Saúde/tendências , China/epidemiologia , Feminino , História do Século XXI , Humanos , Renda , Seguro Saúde/economia , Masculino , Serviços de Saúde Rural/economia , População Rural , Serviços Urbanos de Saúde/economia , População Urbana
12.
Medicine (Baltimore) ; 99(30): e21313, 2020 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-32791720

RESUMO

BACKGROUND: Congenital auricular deformities (CAD) are prevalent worldwide. The objective of this study is to investigate the effectiveness and safety of ear molding for children with CAD at their early days. METHODS: One hundred and nighty children (under 3 days) with CAD will be included in the study. Participants will be randomly allocated to treatment or waiting list group (n = 95). The treatment group will receive ear molding within 3 days after birth for 2 weeks. The control group will receive usual care and receive the same ear molding at 6th week if spontaneously recover is not occur. Physician and parent assessment of improvement, parent's anxiety, depression, and quality of life and adverse events will be measured at baseline, 3rd and 6th week of initial treatment. The primary outcome recovery rate will be compared between groups using Chi square test. Secondary continuous outcomes will be compared using analysis of variance. DISCUSSION: This study is the first randomized controlled trial to examine the effectiveness, safety and cost-effectiveness of ear molding for CAD comparing with waiting list, to inform clinical decision of CAD treatments and relevant guideline development.


Assuntos
Microtia Congênita/epidemiologia , Análise Custo-Benefício/métodos , Orelha/anormalidades , Auxiliares de Audição/efeitos adversos , Estudos de Casos e Controles , Tomada de Decisão Clínica , Orelha/patologia , Auxiliares de Audição/estatística & dados numéricos , Humanos , Recém-Nascido , Pais/psicologia , Qualidade de Vida , Segurança , Resultado do Tratamento , Escala Visual Analógica , Listas de Espera
13.
Neuroscience ; 443: 1-7, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32682823

RESUMO

Amyloid-ß proteins (A ß), including Aß42 and A ß 43, are known pathogenesis factors of Alzheimer's disease (AD). Unwanted substances in the brain, including A ß, are generally removed by microglia, astrocytes, or neurons via a phagocytosis receptor. We observed that neurons and astrocytes engulfed A ß 42 and A ß 43, which are more neurotoxic than A ß 40. We previously showed that multiple-EGF like domains 10 (MEGF10) plays an important role in apoptotic cell elimination and is expressed in mammalian neurons and astrocytes. Therefore, we assessed whether MEGF10 is involved in A ß42 and A ß43 engulfment in MEGF10-expressing neurons and astrocytes. We found that MEGF10-expressing astrocytes and neurons engulfed A ß42 and A ß43 but not A ß40. Furthermore, incubation of the neurons and astrocytes with A ß42 and A ß43a ugmented MEGF10 phosphorylation; however, incubation with A ß40 did not have this augmenting effect. Our findings suggest that MEGF10 plays a phagocytosis receptor function for A ß42 and A ß43 in neurons and astrocytes.

14.
Cell Death Dis ; 11(7): 506, 2020 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-32632098

RESUMO

PD-L1 is overexpressed in tumor cells and contributes to cancer immunoevasion. However, the role of the tumor cell-intrinsic PD-L1 in cancers remains unknown. Here we show that PD-L1 regulates lung cancer growth and progression by targeting the WIP and ß-catenin signaling. Overexpression of PD-L1 promotes tumor cell growth, migration and invasion in lung cancer cells, whereas PD-L1 knockdown has the opposite effects. We have also identified WIP as a new downstream target of PD-L1 in lung cancer. PD-L1 positively modulates the expression of WIP. Knockdown of WIP also inhibits cell viability and colony formation, whereas PD-L1 overexpression can reverse this inhibition effects. In addition, PD-L1 can upregulate ß-catenin by inhibiting its degradation through PI3K/Akt signaling pathway. Moreover, we show that in lung cancer cells ß-catenin can bind to the WIP promoter and activate its transcription, which can be promoted by PD-L1 overexpression. The in vivo experiments in a human lung cancer mouse model have also confirmed the PD-L1-mediated promotion of tumor growth and progression through activating the WIP and ß-catenin pathways. Furthermore, we demonstrate that PD-L1 expression is positively correlated with WIP in tumor tissues of human adenocarcinoma patients and the high expression of PD-L1 and WIP predicts poor prognosis. Collectively, our results provide new insights into understanding the pro-tumorigenic role of PD-L1 and its regulatory mechanism on WIP in lung cancer, and suggest that the PD-L1/Akt/ß-catenin/WIP signaling axis may be a potential therapeutic target for lung cancers.

15.
Nat Prod Res ; : 1-6, 2020 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-32720521

RESUMO

A new phenylpropanoid, ligulaveitnoid A (1), along with four known compounds, (E)-2,3-dihydroconiferyl p-coumarate (2), dihydroconiferyl ferulate (3), 4-hydroxy-3-methoxybenzaldehyde (4) and (E)-p-coumaric acid (5) were isolated from rhizomes and roots of L. veitchiana. All the structures of compounds were identified by the interpretation of their spectroscopic data and comparison with those reported in the literature. The anti-inflammatory activity of the isolates was examined for their inhibitory effects on LPS-induced NO production in macrophage RAW264.7 cells. Among them, compound 2 showed strong inhibitory activities towards the LPS-induced NO production in macrophage RAW264.7 cells with IC50 value of 8.0 µM.

16.
Fitoterapia ; 146: 104652, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32512149

RESUMO

Five sesterterpenes (1-5) including two new compounds (1 and 2), as well as a new (6) and a known macrolide (7) were isolated from the endophytic fungus Aplosporella javeedii. The structures of the new compounds were elucidated by analysis of their 1D and 2D NMR and HRMS data as well as by comparison with the literature. Compound 4 and its acetyl derivatives 4a, 4b, 4c which were prepared by acetylation of 4 exhibited moderate cytotoxicity against the mouse lymphoma cell line L5178Y with IC50 values ranging from 6.2 to 12.8 µM, respectively. Moreover, 4a and 4c exhibited also cytotoxicity against human leukemia (Jurkat J16) and lymphoma (Ramos) cell lines. Compound 7 showed strong cytotoxicity against the L5178Y cell line, as well as against human Jurkat J16 and Ramos cells with IC50 values of 0.4, 5.8, and 4.4 µM, respectively. Mechanistic studies indicated that 7 induces apoptotic cell death. In addition, compounds 3, 4 and 7 showed low antibacterial activities against Mycobacterium tuberculosis H37Rv and compound 6 against Staphylococcus aureus, respectively, with MICs of 100 µM. Preliminary structure-activity relationships are discussed.

17.
Fitoterapia ; 146: 104674, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32561423

RESUMO

Three new sesquiterpenoids (1-3) and four new benzofuran dimers (+)-4 and (-)-4, (+)-5 and (-)-5, and four known benzofuran dimers (+)-6 and (-)-6, (+)-7 and (-)-7 were isolated from the underground parts of Eupatorium chinense. The enantiomers of racemates (±)-4 ~ (±)-7 were separated by chiral HPLC columns, and their absolute configurations were determined by circular dichroism experiments. The structures of all new compounds were elucidated on the basis of their NMR, and MS data as well as by comparison with literature values. The all of the isolated compounds were tested in vitro for their cytotoxic activities against the Caski, MDA-MB-231 and HepG2 cancer cell lines.

18.
Dig Dis Sci ; 2020 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-32591968

RESUMO

BACKGROUND: How gastric cancer (GC) incidence is associated with changes in the gastric microbiome has not been firmly established. The present study therefore aims to investigate the microbial communities present within the gastric mucosa of patients with superficial gastritis (SG) or GC. METHODS: Paired tumor and paracancerous samples of the gastric mucosa were collected from 18 patients being surgically treated for GC and from 32 patients with SG being treated via gastroscopy. The gastric microbiome in these samples was then profiled via 16S rRNA sequencing, with a linear discriminant analysis effect size (LEfSe) approach used to identify and compare different bacteria, and with PICRUSt used for predictive functional analyses. RESULTS: GC patients exhibited a distinct gastric microbiota profile from that observed in SG patients. These changes were evident in both tumor and paracancerous tissues from GC patients. Specifically, we found that 6 bacterial genera were specifically enriched in GC tissue samples relative to SG samples, while 18 genera were depleted in these same samples. Based on the differential abundance of these bacteria, we were able to calculate microbial dysbiosis index (MDI) values, which were significantly higher in GC patients than in SG patients. In addition, MDI values were negatively correlated with gastric Shannon index and were positively correlated with relative Helicobacter spp. abundance. Importantly, these MDI values were readily able to discriminate between GC and SG patient samples. Functional analysis suggested that GC patients were more likely to harbor a nitrosating microbial community. CONCLUSIONS: GC patients exhibited a gastric microbiome profile distinct from that observed in SG patients, with these differences being evident in both tumor and paracancerous tissues. Differences in the relative abundance of Helicobacter spp. may be the primary driver of gastric dysbiosis in GC patients.

19.
FEMS Yeast Res ; 20(5)2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32556321

RESUMO

Yeast autolysis refers to the process in which cells degrade and release intracellular contents under specific conditions by endogenous enzymes such as proteases, nucleases and lipid enzymes. Protein-rich baker's yeast is widely used to produce yeast extract in food industry, however, the molecular mechanism related to baker's yeast autolysis is still unclear. In this study, RNA-seq technology and biochemical analysis were performed to analyze the autolysis processes in baker's yeast. The differentially expressed genes (DEGs), 27 autolysis-related euKaryotic Ortholog Groups (KOG) and three types of autolysis-induced Gene Ontology (GO) were identified and analyzed in detail. A total of 143 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways under autolysis were also assigned. Interestingly, the DEGs were significantly enriched in the mitogen-activated protein kinase (MAPK) signaling pathways and metabolic pathways, and key genes MID2, MTL1, SLT2, PTP2, HKR1 and GPD1 may play important roles in autolysis. Further quantitative PCR was performed to verify the expression pattern in baker's yeast autolysis. Together, all these results indicated that MAPK pathways might play an essential role during autolysis process through inhibiting the metabolism and disrupting cell wall in baker's yeast. This result may provide important clues for the in-depth interpretation of the yeast autolysis mechanism.

20.
J Org Chem ; 85(11): 7485-7493, 2020 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-32400156

RESUMO

Direct N-glycosylation between glycals and amides/amines was achieved with exclusive stereoselectivity in moderate to high yields. Various amides, amines, and 3,4-O-carbonate-glycals were tolerated, and unique ß-N-glycosides were obtained. The strategy was based on palladium-catalyzed decarboxylative allylation, and the high 1,4-cis-selectivity was proposed because of the hydrogen bonding effect. Notably, all the synthesized products were subjected to preliminary bioactivity studies, revealing that three compounds were cytotoxic to tumor cells and nontoxic to normal human cells.

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