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1.
Sci Rep ; 10(1): 3883, 2020 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-32127605

RESUMO

Rhodocyclales is an abundant bacterial order in wastewater treatment systems and putatively plays key roles in multiple functions. Its phylogenomics, prevalence of denitrifying genes in sub-lineages and distribution in wastewater treatment plants (WWTPs) worldwide have not been well characterized. In the present study, we collected 78 Rhodocyclales genomes, including 17 from type strains, non-type strains and genome bins contributed by this study. Phylogenomics indicated that the order could be divided into five family-level lineages. With only a few exceptions (mostly in Rhodocyclaceae), nirS-containing genomes in this order usually contained the downstream genes of norB and nosZ. Multicopy of denitrifying genes occurred frequently and events of within-order horizontal transfer of denitrifying genes were phylogenetically deduced. The distribution of Rhodocyclaceae, Zoogloeaceae and Azonexaceae in global WWTPs were significantly governed by temperature, mixed liquor suspended solids, etc. Metagenomic survey showed that the order generally ranked at the top or second for different denitrifying genes in wastewater treatment systems. Our results provided comprehensive genomic insights into the phylogeny and features of denitrifying genes of Rhodocyclales. Its contribution to the denitrifying gene pool in WWTPs was proved.

2.
Bioconjug Chem ; 31(3): 542-546, 2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32119776

RESUMO

CRISPR-Cas12a, a type-V CRISPR-Cas endonuclease, is an effective genome editing platform. To improve the gene editing efficiency of Cas12a, we rationally designed small molecule enhancers through a combined computational approach. First, we used extensive molecular dynamics (MD) simulations to explore the conformational landscape of Cas12a from Acidaminococcus (AsCas12a), revealing distinct conformational states that could be targeted by small molecules to modulate its genome editing function. We then identified 57 compounds that showed different binding behavior and stabilizing effects on these distinct conformational states using molecular docking. After experimental testing 6 of these 57 compounds, compound 1, quinazoline-2,4(1H,3H)-dione, was found particularly promising in enhancing the AsCas12a-mediated genome editing efficiency in human cells. Compound 1 was shown to act like a molecular "glue" at the interface between AsCas12a and crRNA near the 5'-handle region, thus specifically stabilizing the enzyme-crRNA complex. These results provide a new paradigm for future design of small molecules to modulate the genome editing of the CRISPR-Cas systems.

3.
Artigo em Inglês | MEDLINE | ID: mdl-32100367

RESUMO

Despite the fact that many strategies have been developed to improve the efficiency of the oxygen evolution reaction (OER), the precise modulation of the surface electronic properties of catalysts to improve their catalytic activity is still challenging. Herein, we demonstrate that the surface active electron density of Co3 O4 can be effectively regulated by an argon-ion irradiation method. X-ray photoelectron and synchrotron x-ray absorption spectroscopy, UV photoelectron spectrometry, and DFT calculations show that the surface active electron density band center of Co3 O4 has been upshifted, leading to a significantly enhanced absorption capability of the oxo group. The optimized Co3 O4 -based catalysts exhibit an excellent overpotential of 260 mV at 10 mA cm-2 and Tafel slope of 54 mV dec-1 , superior to the capability of the benchmark RuO2 , representing one of the best Co-based OER catalysts. This approach could guide the future rational design and discovery of ideal electrocatalysts.

4.
Mol Ther Nucleic Acids ; 19: 1043-1052, 2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-32045875

RESUMO

CRISPR-Cas12a (CRISPR-Cpf1) was reported to have multiple types of cleavage activities. Without the assistance of CRISPR RNA (crRNA), we investigated DNase activity and substrate specificity of Cas12a orthologs in the presence of diverse divalent metal ions. Cas12a from different species are capable of degrading single-stranded DNA (ssDNA) and/or double-stranded DNA (dsDNA), depending on the metal ions used. In spite of sharing high sequence similarity and functional domains among diverse Cas12a orthologs, only Acidaminococcus sp. Cas12a (AsCas12a) showed a predominant preference for cleaving ssDNA, but no detectable activity toward dsDNA substrate in the presence of magnesium (II) ions. In addition, we found that both AsCas12a and Francisella novicida Cas12a (FnCas12a) caused substantial dsDNA cleavage in the presence of manganese (II) ion. More importantly, the DNase activities can be inhibited by synthetic DNA oligonucleotides with phosphorothioate linkage modifications. Overall, ssDNase activity of the Cas12a orthologs uncovered a distinct approach for DNA cleavage compared with crRNA-guided dsDNA breaks, and provided insights into potential biological and therapeutic applications.

5.
Nat Nanotechnol ; 15(1): 41-46, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31907443

RESUMO

Sepsis, a condition caused by severe infections, affects more than 30 million people worldwide every year and remains the leading cause of death in hospitals1,2. Moreover, antimicrobial resistance has become an additional challenge in the treatment of sepsis3, and thus, alternative therapeutic approaches are urgently needed2,3. Here, we show that adoptive transfer of macrophages containing antimicrobial peptides linked to cathepsin B in the lysosomes (MACs) can be applied for the treatment of multidrug-resistant bacteria-induced sepsis in mice with immunosuppression. The MACs are constructed by transfection of vitamin C lipid nanoparticles that deliver antimicrobial peptide and cathepsin B (AMP-CatB) mRNA. The vitamin C lipid nanoparticles allow the specific accumulation of AMP-CatB in macrophage lysosomes, which is the key location for bactericidal activities. Our results demonstrate that adoptive MAC transfer leads to the elimination of multidrug-resistant bacteria, including Staphylococcus aureus and Escherichia coli, leading to the complete recovery of immunocompromised septic mice. Our work provides an alternative strategy for overcoming multidrug-resistant bacteria-induced sepsis and opens up possibilities for the development of nanoparticle-enabled cell therapy for infectious diseases.

6.
Leukemia ; 34(1): 35-49, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31439943

RESUMO

Pediatric T cell acute lymphoblastic leukemia (T-ALL) cells frequently contain mutations in the interleukin-7 (IL-7) receptor pathway or respond to IL-7 itself. To target the IL-7 receptor on T-ALL cells, murine monoclonal antibodies (MAbs) were developed against the human IL-7Rα chain and chimerized with human IgG1 constant regions. Crystal structures demonstrate that the two MAbs bound different IL-7Rα epitopes. The MAbs mediated antibody-dependent cell-mediated cytotoxicity (ADCC) against patient-derived xenograft (PDX) T-ALL cells, which was improved by combining two MAbs. In vivo, the MAbs showed therapeutic efficacy via ADCC-dependent and independent mechanisms in minimal residual and established disease. PDX T-ALL cells that relapsed following a course of chemotherapy displayed elevated IL-7Rα, and MAb treatment is effective against relapsing disease, suggesting the use of anti-IL7Rα MAbs in relapsed T-ALL patients or patients that do not respond to chemotherapy.

7.
Talanta ; 208: 120442, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31816734

RESUMO

The application of stir bar sorptive extraction (SBSE) for polar compounds has been restricted because of less choice of suitable sorbents. In this study, an ionic liquid-based organic polymer with desired anionic exchange ability and porous structure was used for extraction of polar analytes with high extraction efficiency and capacity. For improving the workability of stir bar, the polymer was immobilized onto chemically resistant poly(ether ether ketone) (PEEK) tube by covalent modification method which including a skillful functionalization process. Afterwards, a facile detachable dumbbell-shaped structure with modified PEEK tube as jacket was constructed. Due to the excellent chemical and physical strength of PEEK material and dumbbell-shaped structure, the stir bar performed remarkable stability in the SBSE process. In addition, the detachable structure allowed the elution can be accomplished directly in the insert tube of autosampler vial with small amounts of solution, which significantly enhanced the enrichment factor and simplified the operation. After coupling with HPLC-MS/MS, the prepared organic polymer modified stir bar was applied for the analysis of three chlorophenoxy acid herbicides and showed favorable extraction efficiency with enrichment factors between 198 and 206 folds. For quantitative analysis of three chlorophenoxy acid herbicides, the method has wide linear range (0.003-10 ng/mL), good linearity (R2 ≥ 0.9958) and good reproducibility (intra-day relative standard deviation ≤ 6.16%). Furthermore, the proposed method was applied to determine chlorophenoxy acid herbicides in soil samples, the recoveries ranged from 79.4% to 97.4%, with relative standard deviation ≤ 9.3%.

8.
Cancer Cell Int ; 19: 332, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31827406

RESUMO

Background: Abiraterone and MDV3100 are two effective anticancer agents for prostate cancer, however, the mechanism of their downstream action remains undefined. Methods: A dual fluorescent biosensor plasmid was transfected in LNCaP cells to measure mitophagy. The DNA of LNCaP cells was extracted and performed with quantitative real-time PCR to detect mitochondrial DNA copy number. JC-1 staining was utilized to detect the mitochondrial membrane potential and electron microscope was performed to analyze mitochondrial morphology. Moreover, the protein levels of mitochondrial markers and apoptotic markers were detected by western blot. At last, the proliferation and apoptosis of LNCaP cells were analyzed with CCK-8 assay and flow cytometry after abiraterone or MDV3100 treatment. Results: Mitophagy was induced by abiraterone and MDV3100 in LNCaP cells. The low expression level of mitochondrial DNA copy number and mitochondrial depolarization were further identified in the abiraterone or MDV3100 treatment groups compared with the control group. Besides, severe mitochondria swelling and substantial autophagy-lysosomes were observed in abiraterone- and MDV3100-treated LNCaP cells. The expression of mitochondria-related proteins, frataxin, ACO2 and Tom20 were significantly downregulated in abiraterone and MDV3100 treated LNCaP cells, whereas the expression level of inner membrane protein of mitochondria (Tim23) was significantly upregulated in the same condition. Moreover, the proliferation of LNCaP cells were drastically inhibited, and the apoptosis of LNCaP cells was increased in abiraterone or MDV3100 treatment groups. Meanwhile, the addition of mitophagy inhibitor Mdivi-1 (mitochondrial division inhibitor 1) could conversely elevate proliferation and constrain apoptosis of LNCaP cells. Conclusions: Our results prove that both abiraterone and MDV3100 inhibit the proliferation, promote the apoptosis of prostate cancer cells through regulating mitophagy. The promotion of mitophagy might enhance the efficacy of abiraterone and MDV3100, which could be a potential strategy to improve chemotherapy with these two reagents.

9.
Gut ; 2019 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-31857433

RESUMO

OBJECTIVE: Gastrointestinal microbiota may be involved in Helicobacter pylori-associated gastric cancer development. The aim of this study was to explore the possible microbial mechanisms in gastric carcinogenesis and potential dysbiosis arising from H. pylori infection. DESIGN: Deep sequencing of the microbial 16S ribosomal RNA gene was used to investigate alterations in paired gastric biopsies and stool samples in 58 subjects with successful and 57 subjects with failed anti-H. pylori treatment, relative to 49 H . pylori negative subjects. RESULTS: In H. pylori positive subjects, richness and Shannon indexes increased significantly (both p<0.001) after successful eradication and showed no difference to those of negative subjects (p=0.493 for richness and p=0.420 for Shannon index). Differential taxa analysis identified 18 significantly altered gastric genera after eradication. The combination of these genera into a Microbial Dysbiosis Index revealed that the dysbiotic microbiota in H. pylori positive mucosa was associated with advanced gastric lesions (chronic atrophic gastritis and intestinal metaplasia/dysplasia) and could be reversed by eradication. Strong coexcluding interactions between Helicobacter and Fusobacterium, Neisseria, Prevotella, Veillonella, Rothia were found only in advanced gastric lesion patients, and were absent in normal/superficial gastritis group. Changes in faecal microbiota included increased Bifidobacterium after successful H. pylori eradication and more upregulated drug-resistant functional orthologs after failed treatment. CONCLUSION: H. pylori infection contributes significantly to gastric microbial dysbiosis that may be involved in carcinogenesis. Successful H. pylori eradication potentially restores gastric microbiota to a similar status as found in uninfected individuals, and shows beneficial effects on gut microbiota.

10.
Nano Res ; 12(4): 855-861, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31737223

RESUMO

Triple-negative breast cancer (TNBC) is one type of the most aggressive breast cancers with poor prognosis. It is of great urgency to develop new therapeutics for treating TNBC. Based on current treatment guideline and genetic information of TNBC, a combinational therapy platform integrating chemotherapy drugs and mRNA encoding tumor suppressor proteins may become an efficacious strategy. In this study, we developed paclitaxel amino lipid (PAL) derived nanoparticles (NPs) to incorporate both chemotherapy drugs and P53 mRNA. The PAL P53 mRNA NPs showed superior properties compared to Abraxane® and Lipusu® used in the clinic including high paclitaxel loading capacity (24 wt.%, calculated by paclitaxel in PAL), PAL encapsulation efficiency (94.7% ± 6.8%) and mRNA encapsulation efficiency (88.7% ± 0.7%). Meanwhile, these NPs displayed synergetic cytotoxicity of paclitaxel and P53 mRNA in cultured TNBC cells. More importantly, we demonstrated in vivo anti-tumor efficacy of PAL P53 mRNA NPs in an orthotopic TNBC mouse model. Overall, these chemotherapy drugs derived mRNA NPs provide a new platform to integrate chemotherapy and personalized medicine using tumor genetic information, and therefore represent a promising approach for TNBC treatment.

11.
Materials (Basel) ; 12(22)2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31731827

RESUMO

Tobermorite and Al-substituted tobermorite with varying Al/(Si + Al) molar ratios were synthesized via the static hydrothermal method. The effect of different Al substitution ratios on the structure of tobermorite was investigated by XRD, SEM-EDS, TG-DSC, FT-IR, 29Si, and 27Al MAS-NMR. The interplanar crystal spacing of (002) increased with the increment of the Al substitution ratio. The maximum ratio of the Al substitution for Si in the structure of tobermorite was about 15 at %, which was limited by the compositions of tobermorite and the electrostatic repulsive forces caused by Al substitution. The DSC curve of the tobermorite with an Al/(Al + Si) molar ratio of 0.15 showed a larger exothermic peak area at 850 °C, indicating that the Al-O-Si bond was formed in the structure of tobermorite and the Al participated in the recrystallization. The 29Si and 27Al MAS-NMR results confirmed that tetrahedral Al was introduced into the structure of the tobermorite. New silicon sites, Q2(1Al) and Q3(1Al), formed by the Al substitution for Si in bridging and non-bridging sites, were detected. Compared to the tobermorite without Al substitution, the adsorption capacity of Al-substituted tobermorite with Al/(Al + Si) = 0.15 to Na+ was improved by 44%.

12.
Nat Commun ; 10(1): 5230, 2019 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-31745089

RESUMO

The Hengduan Mountains (HDM) biodiversity hotspot exhibits exceptional alpine plant diversity. Here, we investigate factors driving intraspecific divergence within a HDM alpine species Salix brachista (Cushion willow), a common component of subnival assemblages. We produce a high-quality genome assembly for this species and characterize its genetic diversity, population structure and pattern of evolution by resequencing individuals collected across its distribution. We detect population divergence that has been shaped by a landscape of isolated sky island-like habitats displaying strong environmental heterogeneity across elevational gradients, combined with population size fluctuations that have occurred since approximately the late Miocene. These factors are likely important drivers of intraspecific divergence within Cushion willow and possibly other alpine plants with a similar distribution. Since intraspecific divergence is often the first step toward speciation, the same factors can be important contributors to the high alpine species diversity in the HDM.

13.
Oncol Rep ; 42(6): 2788-2796, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31578588

RESUMO

Prostate cancer is closely associated with constitutive transactivation of the androgen receptor (AR) signaling pathway. After treatment with androgen­deprivation therapy (ADT), the majority of patients develop castration­resistant prostate cancer within months or years. In order to investigate potential novel therapeutic targets in addition to ADT, the present study examined the regulatory mechanisms of the AR signaling pathway. In the present study, LNCaP cells were metabolically­labeled with Alk­C16, a palmitate probe. In addition, cells were treated with R1881, an androgen, or DMSO. Subsequently, click­chemistry­based palmitoylome profiling was performed in LNCaP cells and palmitoylated proteins were compared between cells treated with androgen and untreated cells. Androgen treatment was revealed to significantly increase the palmitoylation level of α­tubulin. In addition, the palmitoylation level of Ras­related protein Rab­7a (Rab7a) was enhanced by androgen treatment. Palmitoylation of α­tubulin and Rab7a were essential for cell proliferation. Notably, in the supernatant of LNCaP cells, the palmitoylation level of α­tubulin was also increased following androgen treatment. Palmitoylation of α­tubulin may provide a new potential target for the treatment of prostate cancer. In addition, the high level of α­tubulin palmitoylation in the supernatant may represent a biomarker for early­stage prostate cancer.

14.
Cancer Med ; 8(17): 7431-7445, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31642614

RESUMO

The incidence of breast cancer has increased dramatically in China. We evaluated the clinical and epidemiologic factors associated with breast cancer, and its stage in a case-control study of Northeast Chinese women. We also examined whether these factors were differentially distributed among molecular subtypes of breast cancer in a case-only analysis. We identified 1118 breast cancer patients and 2284 healthy women from Cancer Hospital of Medical University between January 2014 and December 2017. Logistic regression models were used to calculate the odds ratios (ORs) and corresponding 95% confidence intervals (CIs). We found that postmenopausal women had a decreased risk of breast cancer (multivariate-adjusted OR = 0.33, 95% CI:0.25-0.43), and tended to have breast cancer of human epidermal growth factor receptor 2 (HER2)-overexpressing (multivariate-adjusted OR = 2.99, 95% CI: 1.49-5.97) and triple-negative (multivariate-adjusted OR = 2.16, 95% CI: 1.02-4.56) subtypes, compared with the luminal B subtype. Women with history of abortion had an increased risk of breast cancer (multivariate-adjusted OR = 4.70, 95% CI: 3.60-6.14). Women with high breast density and high Breast Imaging Reporting and Data System (BIRADS) scores of lesions tended to have breast cancer of advanced stage, but were not differentially distributed among its molecular subtypes. In conclusion, postmenopausal women had decreased risk of breast cancer, and tended to have nonluminal subtype, while women with history of abortion had increased risk of breast cancer. Women with high breast density and BIRADS scores of lesions tended to have advanced stage breast cancer. We provide evidence on the epidemiologic factors for breast cancer and its subtypes, which may help with breast cancer risk stratification.

15.
BMJ ; 366: l5016, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31511230

RESUMO

OBJECTIVE: To assess the effects of Helicobacter pylori treatment, vitamin supplementation, and garlic supplementation in the prevention of gastric cancer. DESIGN: Blinded randomized placebo controlled trial. SETTING: Linqu County, Shandong province, China. PARTICIPANTS: 3365 residents of a high risk region for gastric cancer. 2258 participants seropositive for antibodies to H pylori were randomly assigned to H pylori treatment, vitamin supplementation, garlic supplementation, or their placebos in a 2×2×2 factorial design, and 1107 H pylori seronegative participants were randomly assigned to vitamin supplementation, garlic supplementation, or their placebos in a 2×2 factorial design. INTERVENTIONS: H pylori treatment with amoxicillin and omeprazole for two weeks; vitamin (C, E, and selenium) and garlic (extract and oil) supplementation for 7.3 years (1995-2003). MAIN OUTCOME MEASURES: Primary outcomes were cumulative incidence of gastric cancer identified through scheduled gastroscopies and active clinical follow-up through 2017, and deaths due to gastric cancer ascertained from death certificates and hospital records. Secondary outcomes were associations with other cause specific deaths, including cancers or cardiovascular disease. RESULTS: 151 incident cases of gastric cancer and 94 deaths from gastric cancer were identified during 1995-2017. A protective effect of H pylori treatment on gastric cancer incidence persisted 22 years post-intervention (odds ratio 0.48, 95% confidence interval 0.32 to 0.71). Incidence decreased significantly with vitamin supplementation but not with garlic supplementation (0.64, 0.46 to 0.91 and 0.81, 0.57 to 1.13, respectively). All three interventions showed significant reductions in gastric cancer mortality: fully adjusted hazard ratio for H pylori treatment was 0.62 (95% confidence interval 0.39 to 0.99), for vitamin supplementation was 0.48 (0.31 to 0.75), and for garlic supplementation was 0.66 (0.43 to 1.00). Effects of H pylori treatment on both gastric cancer incidence and mortality and of vitamin supplementation on gastric cancer mortality appeared early, but the effects of vitamin supplementation on gastric cancer incidence and of garlic supplementation only appeared later. No statistically significant associations were found between interventions and other cancers or cardiovascular disease. CONCLUSIONS: H pylori treatment for two weeks and vitamin or garlic supplementation for seven years were associated with a statistically significant reduced risk of death due to gastric cancer for more than 22 years. H pylori treatment and vitamin supplementation were also associated with a statistically significantly reduced incidence of gastric cancer. TRIAL REGISTRATION: ClinicalTrials.gov NCT00339768.


Assuntos
Infecções por Helicobacter/terapia , Lesões Pré-Cancerosas/terapia , Neoplasias Gástricas/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antiulcerosos/administração & dosagem , Biópsia , China/epidemiologia , Suplementos Nutricionais , Quimioterapia Combinada/métodos , Feminino , Seguimentos , Alho/química , Mucosa Gástrica/microbiologia , Mucosa Gástrica/patologia , Gastroscopia , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/patologia , Helicobacter pylori/isolamento & purificação , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Extratos Vegetais/administração & dosagem , Lesões Pré-Cancerosas/microbiologia , Lesões Pré-Cancerosas/patologia , Inibidores da Bomba de Prótons/administração & dosagem , Neoplasias Gástricas/patologia , Neoplasias Gástricas/prevenção & controle , Análise de Sobrevida , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Vitaminas/administração & dosagem
16.
Angew Chem Int Ed Engl ; 58(46): 16660-16667, 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31489768

RESUMO

An N-doped TiO2 model reveals a conceptually different mechanism for activating the N dopant based on delocalized orbital hybridization through O vacancy incorporation. Synchrotron-based X-ray absorption spectroscopy, time-resolved fluorescence, and DFT studies revealed that O vacancy incorporation can effectively stimulate the delocalization of N impurity states through p-band orbital modulation, which leads to a significant enhancement in photocarrier lifetime. Consequently, this effect also results in a remarkable increase in the incident photon-to-electron conversion efficiency in the range of 400-550 nm compared to that of conventional N-incorporated TiO2 (15 % versus 1 % at 450 nm). This work reveals the fundamental necessity of orbital modulation in the band engineering of metal oxides for driving solar water splitting and beyond.

17.
Cornea ; 38(11): 1430-1437, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31490279

RESUMO

PURPOSE: Basic fibroblast growth factor (bFGF) is an effective drug for corneal injury. However, the explicit role of bFGF in corneal scar formation still remains unclear. Keratinocyte growth factor-2 (KGF-2) is associated with the treatment of wound healing. We aimed to compare the efficacy of bFGF and KGF-2 in prevention of excessive wound healing and consequent scar formation in a rat alkali burn model, which provides important clues on the significance of KGF-2 to be developed as a new drug for such injuries. METHODS: The epithelial defect area was evaluated using fluorescein sodium at a concentration of 0.5%. The therapeutic effect of KGF-2 and bFGF on proliferation of rabbit corneal fibroblasts (RCFs) was evaluated by methylthiazoletetrazolium. RCF migration assays were performed with a modified scratch method. Activation of mitogen-activated protein kinase (MAPK) was evaluated by Western blot with specific antibodies. RESULTS: All corneal wounds treated with KGF-2 were found closed within 7 days; however, the wounds treated with bFGF or phosphate buffer saline (PBS) required 14 days to close. RCFs treated with KGF-2 or bFGF showed similar dose-dependent proliferation. The KGF-2 group significantly promoted cell migration compared with the bFGF group. The KGF-2 group showed less expression of α-smooth muscle actin (SMA) and numbers of myofibroblasts compared with the bFGF group. Our findings suggested identification of cascade reaction of extracellular regulated protein kinases (ERK)1/2 and p38 signals in KGF-2- and bFGF-induced proliferation and migration of RCFs. In addition, KGF-2 showed stronger effects during ERK1/2 and p38 phosphorylation in methylthiazoletetrazolium proliferation assay and scratch migration assay. CONCLUSIONS: KGF-2 exhibited better effects than bFGF in reepithelialization, acceleration of migration, and reduction of scar formation, which has potential to become a new drug to cure corneal injury.

18.
BMC Microbiol ; 19(1): 185, 2019 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-31395013

RESUMO

BACKGROUND: Group B Streptococcus (GBS) is a leading cause of early-onset disease (EOD) and late-onset disease (LOD) in infants. We sought to investigate the antibiotic susceptibility profiles, resistance genes, virulence-related genes, serotype distribution and genotypic characteristics of GBS recovered from infected or colonized neonates and pregnant women in a tertiary teaching hospital in Shenzhen, China, from 2008 to 2015. RESULTS: High resistance rates of erythromycin (66.7-100%) were detected among early-onset GBS (EOGBS), late-onset GBS (LOGBS), neonatal colonizing GBS (NCGBS) and maternal colonizing GBS (MCGBS). 89.5-100% of four groups of GBS isolates showed resistance to tetracycline. More than 90 % of erythromycin resistant isolates of EOGBS (8/8, 100%), LOGBS (16/17, 94.1%) and NCGBS (10/11, 90.9%) harbored ermB, while only 9.1-17.6% harbored mefA/E. By contrast, 55.8% (24/43) and 62.8% (27/43) of erythromycin resistant MCGBS isolates carried ermB and mefA/E genes, respectively. The tetO gene was more common in tetracycline resistant EOGBS (10/11, 90.9%), LOGBS (17/17, 100%) and NCGBS (10/11, 90.9%), compared to tetracycline resistant MCGBS (12/51, 23.5%). Additionally, the tetM gene accounted for 90.9% (10/11), 76.5% (13/17), 45.5% (5/11) and 80.4% (41/51) of four groups of isolates, respectively. Serotype III was the most predominant in EOGBS (8/12, 66.7%) and LOGBS (15/17, 88.2%), while serotype Ib accounted for 50.0% (6/12) of NCGBS, and serotype Ia and III accounted for 45.6% (26/57) and 33.3% (19/57) of MCGBS, respectively. Sequence type 17 (ST17) was the most common in EOGBS (6/12, 50%) and LOGBS (12/17, 70.6%), while ST12 was predominant in NCGBS (5/12, 41.7%), and five STs (ST19, ST23, ST12, ST103 and ST485) accounted for 66.7% (38/57) of the MCGBS. All serotype III-ST17 isolates recovered from neonates were associated with invasive infections. CONCLUSIONS: This study shows the meaningful differences in molecular mechanisms of resistance to erythromycin and tetracycline, and the prevalence of serotypes and STs among GBS recovered from neonates and pregnant women. ST17 is predominant in neonatal invasive GBS, but rare in NCGBS and MCGBS.

19.
JAMA Dermatol ; 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31365038

RESUMO

Importance: Retinoids are bioactive forms of vitamin A that are essential in the maintenance of epithelial maturation and differentiation. Synthetic retinoids are used in chemoprevention of skin cancer among high-risk populations with potential adverse effects. Epidemiologic data on vitamin A intake and risk of cutaneous squamous cell carcinoma (SCC) are limited. Objective: To examine whether vitamin A intake is associated with a reduction in SCC risk. Design, Settings, and Participants: This cohort study prospectively examined intake of vitamin A and carotenoids and SCC risk in the Nurses' Health Study (1984-2012) and the Health Professionals Follow-up Study (1986-2012). Diet was assessed repeatedly. Incident SCC was confirmed by pathologic reports. Data analysis was performed from June 21, 2017, to December 4, 2018. Exposures: Intakes of vitamin A, retinol, and carotenoids. Main Outcomes and Measures: Incident SCC. Cox proportional hazards regression models were used to compute cohort-specific hazard ratios (HRs) and 95% CIs. Pooled HRs of the cohort-specific results were calculated. Results: A total of 3978 SCC cases in 75 170 women in the Nurses' Health Study (mean [SD] age, 50.4 [7.2] years) and 48 400 men in the Health Professionals Follow-up Study (mean [SD] age, 54.3 [9.9] years) were documented. Higher total vitamin A was associated with a reduction in SCC risk; with quintile 1 as the reference, the pooled multivariate HRs for the increasing quintiles of vitamin A intake were 0.97 (95% CI, 0.87-1.07) for quintile 2, 0.97 (95% CI, 0.80-1.17) for quintile 3, 0.93 (95% CI, 0.84-1.03) for quintile 4, and 0.83 (95% CI, 0.75-0.93) for quintile 5 (P < .001 for trend). Higher intakes of retinol and some carotenoids were also associated with a reduction in SCC risk; the pooled HRs for the highest quintiles of intake compared with the lowest quintiles were 0.88 (95% CI, 0.79-0.97; P = .001 for trend) for total retinol, 0.86 (95% CI, 0.76-0.96; P = .001 for trend) for beta cryptoxanthin, 0.87 (95% CI, 0.78-0.96; P < .001 for trend) for lycopene, and 0.89 (95% CI, 0.81-0.99; P = .02 for trend) for lutein and zeaxanthin. The results were generally consistent by sex and other SCC risk factors. Conclusions and Relevance: This study suggests that increased intake of dietary vitamin A is associated with decreased risk of incident SCC. Future studies are needed to determine whether vitamin A supplementation has a role in chemoprevention of SCC.

20.
J Chromatogr A ; 1607: 460403, 2019 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-31378523

RESUMO

MOF-1210(Zr/Cu) is a new heterometallic cluster-based metal-organic framework material as well as a promising solid phase extraction coating material with ordered spatial structure, permanent high porosity and large specific surface area. In this work, a novel MOF-1210(Zr/Cu) modified magnetic nanoparticles (MNPs) was successfully prepared for magnetic solid phase extraction (MSPE) of benzophenones, including 2,4-dihydroxybenzophenone (BP-1), 2-hydroxy-4-methoxybenzophenone (BP-3) and 2,2',4,4'-tetrehydroxybenzophenone (BP-6). The MOF-1210(Zr/Cu)-MNPs were synthesized in one step by a simple solvothermal method and showed high extraction efficiency towards analytes (with enrichment factors of 91-122). The extraction mechanism studies showed that the hydrogen bond interaction and coordination interaction between MOF-1210(Zr/Cu) and BPs played important roles during the extraction process. By coupling with HPLC, the MOF-1210(Zr/Cu)-MNPs-based MSPE-HPLC method showed wide linear range (0.1-300.0 ng·mL-1), good linearity (R ≥ 0.9982), excellent reproducibility (RSD ≤ 3.60%) and remarkable sensitivity (LODs in the range of 0.01-0.02 ng·mL-1). This method was also successfully applied to the extraction and detection of benzophenones in soil samples. Good recoveries were obtained (87.6%-113.8%) with RSDs less than 11.12%, which demonstrated the practicality of the proposed method.


Assuntos
Benzofenonas/análise , Cobre/química , Nanopartículas de Magnetita/química , Estruturas Metalorgânicas/química , Solo/química , Extração em Fase Sólida/métodos , Zircônio/química , Acetonitrilos/química , Ácidos/química , Adsorção , Concentração de Íons de Hidrogênio , Limite de Detecção , Reprodutibilidade dos Testes , Cloreto de Sódio/química , Espectroscopia de Infravermelho com Transformada de Fourier , Fatores de Tempo
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