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1.
Artigo em Inglês | MEDLINE | ID: mdl-33006185

RESUMO

Inspired by the exquisite helices in Nature, fabrication of helical materials with controlled handedness has attracted considerable attention. Herein, we report on precis synthesis of single left- and right-handed helical polyisocyanides through living polymerization of achiral monomers using chiral palladium catalysts under helix-sense-selective manner. Mechanism study revealed that the yielded helices with opposite handedness showed different activity of the living chain end. The helix with unfavoured handedness was self-terminated, while the other one with favoured handedness showed high activity and can undergoes chain propagation to form a high molecular weight polymer with maintained single-handed helicity.

2.
New Phytol ; 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33006771

RESUMO

Post-translational modification of proteins mediated by SIZ1, a small ubiquitin-like modifier (SUMO) E3 ligase, regulates multiple biological processes in plants. However, its role in the regulation of lateral root formation remains unclear. Here, we demonstrate that the apple SUMO E3 ligase MdSIZ1 promotes lateral root formation. Using a yeast two-hybrid system, the auxin response factor MdARF8 was screened out as a protein-protein interaction partner of the SUMO-conjugating E2 enzyme MdSCE1, indicating that MdARF8 may be a substrate for MdSIZ1. The interaction between MdARF8 and MdSCE1 was confirmed by pull-down, Y2H, and Co-IP assays. MdSIZ1 enhanced the conjugating enzyme activity of MdSCE1 to form a MdSCE1-MdSIZ1-MdARF8 complex, thereby facilitating SUMO modification. We identified two arginine substitution mutations at K342 and K380 in MdARF8 that blocked MdSIZ1-mediated SUMOylation, indicating that K342 and K380 are the principal SUMOylation sites of the MdARF8 protein. Moreover, MdARF8 promoted lateral root formation in transgenic apple plants, and the phenotype of reduced lateral roots in the Arabidopsis siz1-2 mutant was restored in siz1-2/MdARF8 complementary plants. Our findings reveal an important role for sumoylation in the regulation of lateral root formation in plants.

3.
J Clin Lab Anal ; : e23594, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33009702

RESUMO

BACKGROUND: TTC32-WDR35 gene cluster has been genome-wide significantly associated with coronary artery disease (CAD). However, the common variants in this region contributing to CAD risk remain elusive. METHODS: We performed a case-control study enrolling 935 CAD cases and 935 age-sex-frequency-matched controls from unrelated southwest Chinese Han population. Five variants were determined by TaqMan assay. RESULTS: This study indicated that rs721932 CG genotype was associated with CAD risk (OR = 0.68, 95% CI: 0.54-0.86; P = .001). Stratified analysis showed that the risk associated with rs12617744 AA genotype was robust in male (OR = 0.62, 95% CI: 0.42-0.93, P = .02). The gene dosage of the risk allele at rs12617744 showed a significant association with left circumflex artery disease (P = .027) and the number of vascular lesions in patients (P = .034). Moreover, the gene dosage of rs721932 risk allele was associated with vascular lesion numbers (P = .048) and the progression of CAD (P = .028). Compared with carriers of major alleles, the AA genotype of rs12617744 and GG genotype of rs721932 were both associated with plasma HDL level (P = .009 and 0.004, respectively). Expression quantitative trait locus (eQTL) results showed significantly different TTC32 expression of subjects as a function of SNPs (rs2278528, rs7594214, and rs721932) genotype in the artery. Besides, FPRP analysis did support the strong links between polymorphisms and CAD risk. CONCLUSIONS: SNP rs721932 at TTC32-WDR35 Gene Cluster was associated with CAD risk, and rs12617744 was associated with the risk of CAD among males. Both SNPs may contribute to the regulation of plasma HDL levels and possibly to the severity of CAD in Chinese Han population.

4.
Front Immunol ; 11: 2176, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33013914

RESUMO

Chemokine receptor cxcr4 and its ligand cxcl12 have evolved two paralogs in the teleost lineage. In this study, we have identified four duplicated cxcr4 and cxcl12 genes from hexaploid gibel carp, Carassius gibelio, respectively. Cgcxcr4bs and Cgcxcl12as were dynamically and differentially expressed in immune-related tissues, and significantly up-regulated in head kidney and spleen after crucian carp herpesvirus (CaHV) infection. Blocking Cxcr4/Cxcl12 axis by injecting AMD3100 brought more severe bleeding symptom and lower survival rate in CaHV-infected fish. AMD3100 treatment also suppressed the up-regulation of key antiviral genes in head kidney and spleen, and resulted in more acute replication of CaHV in vivo. Consistently, the similar suppression of up-regulated expression of key antiviral genes were also observed in CAB cells treated by AMD3100 after poly(I:C) stimulation. Finally, MAPK3 and JAK/STAT were identified as the possible pathways that CgCxcr4s and CgCxcl12s participate in to promote the antiviral response in vitro.

5.
Exp Cell Res ; : 112317, 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33038351

RESUMO

Ubiquitin-specific protease 4 (USP4), has been reported to participate in the progression of various cancers due to its role in post-translational modulation. However, the prognostic significance and mechanism of USP4 in pancreatic cancer (PC) have not been well elucidated before. In the present study, we found that USP4 expression was higher in PC tissues than that in adjacent normal tissues and PC patients with high level of USP4 expression have a poor prognosis via immunohistochemistry and bioinformatics analyses. In vitro study showed that knockdown of USP4 inhibited PC cells proliferation, migration and invasion. Mechanistically, USP4 can activate nuclear factor kappa-B signaling pathway via stabilizing TNF receptor associated factor 6 at its protein level to promote the ability of proliferation, migration and invasion of PC cells. The results of this study revealed that USP4 plays a tumor-promoting role in PC and can be used as a prognostic indicator and therapeutic target for patients with resected PC.

6.
Gene ; : 145204, 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33031890

RESUMO

Germ cells are essential for gonadal development. As precursors of germ cells, primordial germ cells (PGCs) are particularly important for germline formation. However, the research on distribution patterns of PGCs in marine fish is very limited, especially for economic species. The vasa gene has been widely used as marker to identify PGCs origination and migration because of vasa RNA is a component of germ plasm. In this study, we isolated full-length vasa cDNA (Omvas and Pmvas) from marine medaka (Oryzias melastigma) and red seabream (Pagrus major), detected vasa transcripts in different tissues by RT-PCR and described vasa expression patterns during embryogenesis and gametogenesis by in situ hybridization. At the same time, we also explored the relationship between early distribution of germ plasm components and species evolution. The results demonstrated that deduced amino acid sequence of Omvas and Pmvas shared several conserved motifs of Vasa homologues and high identity with other teleost, and vasa transcripts were exclusively detected in early germ cells of gonad. During embryogenesis, vasa RNA of both fishes, like medaka (Oryzias latipes), failed to localize at cleavage furrows and distributed uniformly throughout each blastomere. This study firstly discovered that the marine economic fish, red seabream, lost vasa RNA early specific localization at cleavage furrows and distinctive distribution in germ cells. In addition, compared with other teleost, we found that early distribution of germ plasm might not relate to species evolution. This will improve our understanding of vasa localization modes in teleost, and facilitate fish germ cell manipulation.

7.
Infection ; 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33037572

RESUMO

CASE PRESENTATION: We report the first confirmed case of the novel coronavirus disease (COVID-19) in a lactating patient in Chizhou, Anhui Province, China. The lactating patient presented with intermittent fever for 16 days and cough for 10 days. Given her travel history to the epidemic area and the chest CT scan results, the patient was immediately admitted to the isolation ward of the Infectious Disease Department and breastfeeding was discontinued. Pharyngeal swab specimens tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, previously known as 2019-nCoV) in nucleic acid testing. During hospitalization, she also experienced bilateral breast tenderness. After active treatment, the patient ultimately achieved remission and was discharged from the hospital. DISCUSSION AND CONCLUSIONS: SARS-CoV-2 is transmitted mainly through respiratory droplets and patient contact, rendering the general population to a high risk of infection. The management of mother-child interactions and breastfeeding in women with COVID-19 is a difficult problem. The purpose of this case report is to help clinicians by improving the understanding of COVID-19, particularly in lactating patients.

8.
Biosci Rep ; 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33030206

RESUMO

Oocyte maturation is a prerequisite for successful fertilization and embryo development. Incomplete oocyte maturation can result in infertility. Ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) has been found to be implicated in oocyte maturation and embryo development. However, the cellular and molecular mechanisms of UCH-L1 underlying oocyte maturation have not been fully elucidated. In the present study, we observed that the introduction of UCH-L1 inhibitor LDN-57444 suppressed first polar body extrusion during mouse oocyte maturation. The inhibition of UCH-L1 by LDN-57444 led to the notable increase of reactive oxygen species (ROS) level, conspicuous reduction of glutathione (GSH) content and mitochondrial membrane potential (MMP), and blockade of spindle body formation. As a conclusion, UCH-L1 inhibitor LDN-57444 suppressed mouse oocyte maturation by improving oxidative stress, attenuating mitochondrial function, curbing spindle body formation and down-regulating ERK1/2 expression, providing a deep insight into the cellular and molecular basis of UCH-L1 during mouse oocyte maturation.

9.
Cell Death Dis ; 11(10): 857, 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33057008

RESUMO

Poor viability of mesenchymal stem cells (MSCs) at the transplanted site often hinders the efficacy of MSCs-based therapy. Platelet lysate (PL) contains rich amounts of growth factors, which benefits cell growth. This study aimed to explore how human PL benefits umbilical cord-derived MSCs (huc-MSCs), and whether they have synergistic potential in osteoarthritis (OA) treatment. As quality control, flow cytometry and specific staining were performed to identify huc-MSCs, and ELISA was used to quantify growth factors in PL. CCK-8 and flow cytometry assays were performed to evaluate the effects of PL on the cell viability and cell cycle progression of huc-MSCs. Wound healing and transwell assays were conducted to assess the migration of huc-MSCs. RNA sequencing, real time PCR, and Western blot assays were conducted to explore the growth factors-based mechanism of PL. The in vitro results showed that PL significantly promoted the proliferation, cell cycle, and migration of huc-MSCs by upregulating relevant genes/proteins and activating beclin1-dependent autophagy via the AMPK/mTOR signaling pathway. The main growth factors (PDGF-AA, IGF-1, TGF-ß, EGF, and FGF) contributed to the effects of PL in varying degrees. The in vivo data showed that combined PL and huc-MSCs exerted significant synergistic effect against OA. The overall study determined the beneficial effects and mechanism of PL on huc-MSCs and indicated PL as an adjuvant for huc-MSCs in treating OA. This is the first report on the growth factors-based mechanism of PL on huc-MSCs and their synergistic application. It provides novel knowledge of PL's roles and offers a promising strategy for stem cell-based OA therapy by combining PL and huc-MSCs.

10.
PLoS Genet ; 16(10): e1008627, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33057400

RESUMO

Mating-type switching is a complex mechanism that promotes sexual reproduction in Saccharomycotina. In the model species Saccharomyces cerevisiae, mating-type switching is initiated by the Ho endonuclease that performs a site-specific double-strand break (DSB) at MAT, repaired by homologous recombination (HR) using one of the two silent mating-type loci, HMLalpha and HMRa. The reasons why all the elements of the mating-type switching system have been conserved in some Saccharomycotina, that do not show a sexual cycle nor mating-type switching, remain unknown. To gain insight on this phenomenon, we used the yeast Candida glabrata, phylogenetically close to S. cerevisiae, and for which no spontaneous and efficient mating-type switching has been observed. We have previously shown that expression of S. cerevisiae's Ho (ScHo) gene triggers mating-type switching in C. glabrata, but this leads to massive cell death. In addition, we unexpectedly found, that not only MAT but also HML was cut in this species, suggesting the formation of multiple chromosomal DSBs upon HO induction. We now report that HMR is also cut by ScHo in wild-type strains of C. glabrata. To understand the link between mating-type switching and cell death in C. glabrata, we constructed strains mutated precisely at the Ho recognition sites. We find that even when HML and HMR are protected from the Ho-cut, introducing a DSB at MAT is sufficient to induce cell death, whereas one DSB at HML or HMR is not. We demonstrate that mating-type switching in C. glabrata can be triggered using CRISPR-Cas9, without high lethality. We also show that switching is Rad51-dependent, as in S. cerevisiae, but that donor preference is not conserved in C. glabrata. Altogether, these results suggest that a DSB at MAT can be repaired by HR in C. glabrata, but that repair is prevented by ScHo.

11.
Nephrology (Carlton) ; 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33058364

RESUMO

OBJECTIVE: The present study aimed to investigate the value of calcium-mediated parathyroid hormone (PTH) suppression test in evaluating the autonomic secretory function of parathyroid, and the management of uremic secondary hyperparathyroidism (SHPT). METHODS: Calcium-mediated PTH suppression test was performed in dialysis with SHPT, who were candidates for parathyroidectomy from June 2017 to December 2019 in our hospital. The PTH inhibition rate (PTH-IR) was calculated, and the correlation between PTH-IR and clinical indicators was explored. RESULTS: Fifty-one subjects were included. PTH-IR was negatively correlated with baseline PTH (r =-0.35, p=0.012), it was also correlated with dialysis years, coronary artery calcification score(CACS), and parathyroid mass (r =-0.397, p =0.004; r =-0.327, p=0.028;r =-0.363, p=0.015), which were not found for baseline PTH. Forty-four patients underwent surgical treatment. According to the histological results, twenty-six patients presented with parathyroid non-nodular hyperplasia, eighteen patients presented with parathyroid nodular hyperplasia. The mass of parathyroid of patients with nodular hyperplasia was higher than that of patients with non-nodular hyperplasia (ρ=0.01). The difference of the PTH-IR was not found between the two groups (ρ = 0.296). During the test, the highest serum calcium was 2.9±0.4mmol/L, which dropped to normal at the end of the test. CONCLUSIONS: PTH-IR might be a useful indicator in evaluating the autonomic secretory function of parathyroid and the progression of SHPT on top of iPTH. Calcium-mediated PTH suppression test was safe in uremic secondary hyperparathyroidism patients, but need to monitor for transient hypercalcemia.

12.
Artigo em Inglês | MEDLINE | ID: mdl-33044052

RESUMO

AIMS: Interleukin-35 (IL-35), a novel anti-inflammatory cytokine, has recently been implicated in tumor development, progression, and survival. However, the relationship between serum IL-35 levels and gastric cancer (GC) is inconclusive. Here, we performed this study to clarify the role of serum level of IL-35 in GC patients. METHODS: We enrolled 180 GC patients and 170 healthy controls and used enzyme-linked immunosorbent assay to detect serum IL-35 levels. The clinical relevance between IL-35 and clinical pathology parameters was assessed. Univariate and multivariate logistic regressions were used to determine the feasibility of IL-35 as a clinical biomarker. RESULTS: We observed that serum IL-35 levels were significantly higher in GC patients (17.559 ± 13.266 pg/mL) than in healthy controls (8.077 ± 3.801 pg/mL, P < .001). High serum IL-35 levels were significantly associated with clinical stage (P = .048) and Helicobacter pylori (HP) infection (P < .001). The Kaplan-Meier survival analysis indicated that patients in the high-IL-35 group had poor overall survival (OS) and progression-free survival (PFS) (median OS: 26.0 vs 36.0 months, P < .001; median PFS: 18.0 vs.26.0 months, P = .044). Multivariate analyses demonstrated that serum IL-35 was an independent prognostic factor for GC (OS: hazard ratio [HR] = 1.031 [95% CI, 1.017-1.045], P < .001; PFS: HR = 1.029 [95% CI, 1.015-1.043], P < .001). CONCLUSIONS: High serum IL-35 levels are associated with poor disease prognosis in GC patients, and it may be become a new and promising biomarker for prognosis of gastric cancer.

13.
Artigo em Inglês | MEDLINE | ID: mdl-33011300

RESUMO

BACKGROUND: Vancomycin, the most common antimicrobial used in US hospitals, can cause diverse adverse reactions, including hypersensitivity reactions (HSRs). Yet, little is known about vancomycin reactions documented in electronic health records. OBJECTIVE: To describe vancomycin HSR epidemiology from electronic health record allergy data. METHODS: This was a cross-sectional study of patients with 1 or more encounter from 2017 to 2019 and an electronic health record vancomycin drug allergy label (DAL) in 2 US health care systems. We determined prevalence and trends of vancomycin DALs and assessed active DALs by HSR phenotype determined from structured (coded) and unstructured (free-text) data using natural language processing. We investigated demographic associations with documentation of vancomycin red man syndrome (RMS). RESULTS: Among 4,490,618 patients, 14,426 (0.3%) had a vancomycin DAL with 18,761 documented reactions (2,248 [12.0%] free-text). Quarterly mean vancomycin DALs added were 253 ± 12 and deleted were 12 ± 2. Of 18,761 vancomycin HSRs, 7,903 (42.1%) were immediate phenotypes and 3,881 (20.7%) were delayed phenotypes. Common HSRs were rash (32% of HSRs) and RMS (16% of HSRs). Anaphylaxis was coded in 6% cases of HSRs. Drug reaction eosinophilia and systemic symptoms syndrome was the most common coded vancomycin severe cutaneous adverse reaction. RMS documentation was more likely for males (odds ratio, 1.30; 95% CI, 1.17-1.44) and less likely for blacks (odds ratio, 0.59; 95% CI, 0.47-0.75). CONCLUSIONS: Vancomycin causes diverse adverse reactions, including common (eg, RMS) and severe (eg, drug reaction eosinophilia and systemic symptoms syndrome) reactions entered as DAL free-text. Anaphylaxis comprised 6% of documented vancomycin HSRs, although true vancomycin IgE-mediated reactions are exceedingly rare. Improving vancomycin DAL documentation requires more coded entry options, including a coded entry for RMS.

14.
BMC Pulm Med ; 20(1): 270, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33066754

RESUMO

BACKGROUND: Severe asthma is a chronic disease contributing to disproportionate disease morbidity and mortality. From the year of 2007, many genome-wide association studies (GWAS) have documented a large number of asthma-associated genetic variants and related genes. Nevertheless, the molecular mechanism of these identified variants involved in asthma or severe asthma risk remains largely unknown. METHODS: In the current study, we systematically integrated 3 independent expression quantitative trait loci (eQTL) data (N = 1977) and a large-scale GWAS summary data of moderate-to-severe asthma (N = 30,810) by using the Sherlock Bayesian analysis to identify whether expression-related variants contribute risk to severe asthma. Furthermore, we performed various bioinformatics analyses, including pathway enrichment analysis, PPI network enrichment analysis, in silico permutation analysis, DEG analysis and co-expression analysis, to prioritize important genes associated with severe asthma. RESULTS: In the discovery stage, we identified 1129 significant genes associated with moderate-to-severe asthma by using the Sherlock Bayesian analysis. Two hundred twenty-eight genes were prominently replicated by using MAGMA gene-based analysis. These 228 replicated genes were enriched in 17 biological pathways including antigen processing and presentation (Corrected P = 4.30 × 10- 6), type I diabetes mellitus (Corrected P = 7.09 × 10- 5), and asthma (Corrected P = 1.72 × 10- 3). With the use of a series of bioinformatics analyses, we highlighted 11 important genes such as GNGT2, TLR6, and TTC19 as authentic risk genes associated with moderate-to-severe/severe asthma. With respect to GNGT2, there were 3 eSNPs of rs17637472 (PeQTL = 2.98 × 10- 8 and PGWAS = 3.40 × 10- 8), rs11265180 (PeQTL = 6.0 × 10- 6 and PGWAS = 1.99 × 10- 3), and rs1867087 (PeQTL = 1.0 × 10- 4 and PGWAS = 1.84 × 10- 5) identified. In addition, GNGT2 is significantly expressed in severe asthma compared with mild-moderate asthma (P = 0.045), and Gngt2 shows significantly distinct expression patterns between vehicle and various glucocorticoids (Anova P = 1.55 × 10- 6). CONCLUSIONS: Our current study provides multiple lines of evidence to support that these 11 identified genes as important candidates implicated in the pathogenesis of severe asthma.

15.
J Stroke Cerebrovasc Dis ; 29(11): 105274, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33066887

RESUMO

BACKGROUND AND OBJECTIVE: Cerebral venous thrombosis (CVT) is not rare in women of childbearing age. Chinese couples have been encouraged to have two children by the new family-planning policy. Concerns have been raised about the effect of CVT on subsequent pregnancies, but few studies have focused on the Chinese population. We aimed to analyze the clinical features of Chinese female CVT patients of childbearing age and study the outcome of their subsequent pregnancies after CVT. METHODS: We retrospectively analyzed the clinical data of female patients at fertile age (15-45 years) diagnosed with CVT in our hospital between January 2009 and January 2019. Information on recurrence of venous thrombotic events as well as obstetrical outcomes of subsequent pregnancies was obtained and evaluated during follow-up. RESULTS: A total of 72 patients were enrolled, mean age at CVT onset was 29.4 ± 7.9 years. The main risk factors included autoimmune system disease (27.8%), pregnancy or puerperium (12.5%), and inherited thrombophilia (11.1%). Furthermore, 58 patients were followed up for a mean time of 63.1 ± 31.4 months and 17 new pregnancies occurred in 13 women. Among the 17 pregnancies, one CVT (5.9%) recurred in a patient with antiphospholipid syndrome. Overall, 10 (58.8%) pregnancies resulted in the birth of healthy children, including 8 full-term and 2 preterm births; 7 were terminated, including 3 (17.6%) spontaneous abortions. All patients with spontaneous abortions had antiphospholipid syndrome or Behcet's disease. CONCLUSIONS: Autoimmune system disease was the most common risk factor in Chinese female CVT patients. Recurrent pregnancy-associated CVT was infrequent in women with prior CVT, but attention should be paid during subsequent pregnancies.

16.
J Invest Surg ; : 1-6, 2020 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-32865062

RESUMO

OBJECTIVE: To compare the efficacy and safety of iodine-125 seed interstitial brachytherapy and local chemotherapy perfusion in treatment of advanced pancreatic cancer. METHODS: The present open prospective randomized control study included a total of 165 cases of advanced pancreatic cancer patients who were admitted in our hospital during December 2016 to April 2019. All patients were randomized into two groups with 84 cases in iodine-125 group and 81 cases in chemotherapy perfusion group. Basic clinical characteristics and demographic data were collected. The main outcome was the tumor efficiency. The pain condition was measured by visual analogue scale (VAS) and the Karnofsky score was also measured at different time points, before the treatment, 1 d, 7 d, 14 d, 1 mon, 2 mon and 3 mon after treatment. Serum levels of CEA, CA19-9 and CA50 were measured by immunochemiluminescence. The overall survival was analyzed by K-M curve. RESULTS: The ratio of partial remission patients was significantly higher, and the ratio of stable disease (SD)+progressive disease patients was also remarkably lower in iodine-125 group than the chemotherapy perfusion group. The mean VAS scores decreased markedly after treatment and were significantly lower and the mean Karnofsky scores were remarkably higher in iodine-125 group than the chemotherapy perfusion group. The levels of CA19-9 and CA50 were remarkably lower in iodine-125 group, however no significant difference was found for CEA. The survival analysis by K-M curve showed the iodine-125 patients had longer overall survival time than the chemotherapy perfusion group. No infection, pancreatic fistula, biliary fistula, intestinal fistula, gastrointestinal obstruction or radiation enteritis was found in both groups. CONCLUSION: Iodine-125 seed interstitial brachytherapy could achieve better efficacy with no increased side complications than chemotherapy perfusion in advanced pancreatic cancer.

17.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 36(3): 268-272, 2020 May.
Artigo em Chinês | MEDLINE | ID: mdl-32981284

RESUMO

Objective: To explore the effects of obatoclax(OBX) combined with gemcitabine(GEM) on breast cancer cells MCF-7 and BT-20 cell activity, migration, invasion and apoptosis under hypoxia condition.Methods: Breast cancer cells MCF-7 and BT-20 were divided into normal group, hypoxia group, GEM group, OBX+GEM group. Normal group: Cells were cultured at 37℃, 5% CO2 for 24 h and 48 h; Hypoxia group: Cells were cultured at 37℃, 1% O2, 5% CO2, 94% N2 for 24 h and 48 h; GEM group: Cells were cultured at 37℃, 1% O2, 5% CO2, 94% N2, adding 10 µmol/L GEM for 24 h and 48 h; OBX + GEM group: Cells were cultured at 37℃, 1% O2, 5% CO2, 94% N2, adding 10 µmol/L GEM and 50 nmol/L OBX for 24 h and 48 h. Western blot method was used to detect the expressions of HIF-1α in MCF-7 and BT-20 cells under normal oxygen and hypoxia condition. CCK-8 method was used to detect cancer cell activity, each group was provided with 15 compound holes. Scratch experiment was used to detect cells migration ability, each group was provided with 6 compound holes. Western blot method was used to detect the expressions of vimentin, E-Cadherin and p53 protein in cells of each group. Results: Under hypoxia condition, the expression of HIF-1α in MCF-7 and BT-20 cells was much higher than that under normal oxygen(P<0.05). Compared with hypoxia group, GEM could reduce MCF-7 and BT-20 cells migration ability(P<0.01)and cell activity(P<0.05), while decrease the expression of vimentin protein(P<0.01)and promote the expressions of E-Cadherin (P<0.01)and p53 protein(P<0.01) in tumor cells under hypoxia condition. In OBX combined with GEM group, the cell activity and the migration ability of MCF-7 and BT-20 were reduced significantly(P<0.01). The expression of vimentin in cells was further reduced(P<0.01). The expressions of E-Cadherin(P<0.01)and p53(P<0.01) protein were increased significantly compared with GEM group. Conclusion: Under hypoxia condition, OBX combined with a low-dose of GEM can significantly inhibit the growth, migration and invasion of breast cancer cells, and enhance the pro-apoptotic effect of GEM, but the specific mechanism needs further study.

18.
Food Chem ; 339: 127856, 2020 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-32866698

RESUMO

Egg yolk phospholipids from seven different species were purified (purity > 96%) using SPE columns, and subsequently the phospholipid profiles were identified and quantified by ultra-high-performance liquid chromatography-electrospray ionization-triple time-of flight mass spectrometry (UHPLC-ESI-Triple TOF-MS). Eight phospholipid classes and 87 molecular species were characterized. Principal component analysis showed that the molecular species and concentration of phospholipids in pigeon and hen egg yolks had a significant difference with other eggs. Hierarchical cluster analysis indicated that the phospholipid profiles of pigeon egg yolks were closest to hen egg yolks, followed by quail, duck, ostrich, emu and goose egg yolks. Different relative quantities of certain molecular species were different among egg yolk types; for instance, phosphatidylcholine (16:0/16:1) in goose egg yolks and phosphatidylethanolamine (16:0/18:3) in ostrich egg yolks. This study provides a basis for a better understanding of the phospholipid profiles of egg yolks, and better evaluation of the nutritional value of eggs.

19.
Artigo em Inglês | MEDLINE | ID: mdl-32926650

RESUMO

This study focused on the role of methionine (MET) in the autophagy of gastric cancer stem cells (GCSCs) and aims to elaborate its regulatory mechanism. In the present study, the GCSCs were isolated from human gastric cancer cell lines using an anti-CD44 antibody, and then cultured in MET+ homocysteine (HCY)- or MET-HCY+ medium. In MET+HCY-treated GCSCs, autophagy was suppressed, the methylation and phosphorylation of RAB37 were elevated, and miR-200b expression was down-regulated. Lentiviral vector (LV-) carrying methionine-γ lyase (an enzyme that could specifically lyse MET; Metase) promoted autophagy, reduced the methylation and phosphorylation of RAB37, and up-regulated miR-200b expression in MET+HCY--treated GCSCs. Then, we found that miR-200b suppressed the expression of protein kinase C α (PKCα), a protein that could inactivate RAB37 through promoting its phosphorylation. LV-Metase down-regulated RAB37 phosphorylation via miR-200b/PKCα, thus promoting the RAB37-mediated autophagy and suppressing cell viability in MET+HCY-treated GCSCs. Finally, the in vivo study proved that LV-Metase treatment inhibited tumor growth through up-regulating RAB37 expression. In conclusion, MET suppressed RAB37 expression via enhancing its methylation and suppressed RAB37 activity via miR-200b/PKCα axis, thus repressing RAB37-mediated autophagy in GCSCs. The supplementation of Metase lysed MET, thus inducing the autophagy of GCSCs and inhibiting tumor growth.

20.
Artigo em Inglês | MEDLINE | ID: mdl-32954573

RESUMO

Liquid metal nanodroplets not only share similar metallic properties and nanoscale effect with solid metal nanoparticles, but also possess the additional uniqueness in nonvolatile fluidity and ambient sintering ability into continuous conductors. In most cases, liquid metal nanodroplets are encapsulated into ultrathin and fragile shells of oxides and amphiphile monolayers, and may be hindered from incorporating homogeneously into various composites through conventional processing methods. In this study, ring-opening polymerization is found to be initiated by sonicating the liquid metal EGaIn in fluidic lactones. By this in situ polymerization, EGaIn nanodroplets are encapsulated into polylactone shells with tunable thickness, which can further be dried into a solid powder. Besides high chemical stability and dispersibility in organic solvents, the powder of the EGaIn capsules combines the exceptional properties of the EGaIn droplets (e.g., photothermal effect) and the polylactone shells (e.g., biocompatibility, biodegradability, and compatibility with different polymer matrixes), being capable of being introduced into thermoplastic composites through liquid casting and thermal- or photomolding for the notch-insensitive tearing property, sintering-induced electric conductivity, and photothermal effect. Thus, the EGaIn initiator of ring-opening polymerization may start a pathway to produce stable andthermal/photomoldable powders of EGaIn capsules and their multifunctionalcomposites, applicable in biomedicines, soft electronics, and smart robots.

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