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1.
Chin Med J (Engl) ; 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32004165

RESUMO

BACKGROUND: Human infections with zoonotic coronaviruses (CoVs), including severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV, have raised great public health concern globally. Here, we report a novel bat-origin CoV causing severe and fatal pneumonia in humans. METHODS: We collected clinical data and bronchoalveolar lavage (BAL) specimens from five patients with severe pneumonia from Jin Yin-tan Hospital of Wuhan, Hubei province, China. Nucleic acids of the BAL were extracted and subjected to next-generation sequencing. Virus isolation was carried out, and maximum-likelihood phylogenetic trees were constructed. RESULTS: Five patients hospitalized from December 18 to December 29, 2019 presented with fever, cough, and dyspnea accompanied by complications of acute respiratory distress syndrome. Chest radiography revealed diffuse opacities and consolidation. One of these patients died. Sequence results revealed the presence of a previously unknown ß-CoV strain in all five patients, with 99.8% to 99.9% nucleotide identities among the isolates. These isolates showed 79.0% nucleotide identity with the sequence of SARS-CoV (GenBank NC_004718) and 51.8% identity with the sequence of MERS-CoV (GenBank NC_019843). The virus is phylogenetically closest to a bat SARS-like CoV (SL-ZC45, GenBank MG772933) with 87.6% to 87.7% nucleotide identity, but is in a separate clade. Moreover, these viruses have a single intact open reading frame gene 8, as a further indicator of bat-origin CoVs. However, the amino acid sequence of the tentative receptor-binding domain resembles that of SARS-CoV, indicating that these viruses might use the same receptor. CONCLUSION: A novel bat-borne CoV was identified that is associated with severe and fatal respiratory disease in humans.

2.
J Vis Exp ; (156)2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32065162

RESUMO

This report described sample preparation methods that scanning and transmission electron microscope observations, demonstrated by preparing appendages of the woodboring beetle, Chlorophorus caragana Xie & Wang (2012), for both types of electron microscopy. The scanning electron microscopy (SEM) sample preparation protocol was based on sample chemical fixation, dehydration in a series of ethanol baths, drying, and sputter-coating. By adding Tween 20 (Polyoxyethylene sorbitan laurate) to the fixative and the wash solution, the insect body surface of woodboring beetle was washed more cleanly in SEM. This study's transmission electron microscopy (TEM) sample preparation involved a series of steps including fixation, ethanol dehydration, embedding in resin, positioning using fluorescence microscopy, sectioning, and staining. Fixative with Tween 20 enabled penetrate the insect body wall of woodboring beetle more easily than it would had been without Tween 20, and subsequently better fixed tissues and organs in the body, thus yielded clear transmission electron microscope observations of insect sensilla ultrastructures. The next step of this preparation was determining the positions of insect sensilla in the sample embedded in the resin block by using fluorescence microscopy to increase the precision of target sensilla positioning. This improved slicing accuracy.

3.
Sci Rep ; 10(1): 2604, 2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32054869

RESUMO

Although postoperative cholangioscopy (POC) guided electrohydraulic lithotripsy (EHL) is considered to be a conventional technique for residual biliary calculi, its efficacy still needs to be improved to fit in the managemet of refractory calculi. This study evaluated the efficacy and safety of combined lithotripsy of mechanical clamping and electrohydraulics in fragmentation and removal of refractory calculi. Totally, 281 patients, who suffered from residual biliary calculi after hepatectomy and underwnet POC from August 2016 to June 2018 were involved. The first 128 patients were subjected to conventional EHL, and later consective 153 to combined lithotripsyof mechanical clamping and EHL. Perioperative data, technical information, treatment outcomes and follow-up results were collected. Clinical characteristics were statistically comparable (P > 0.05). The overall POC interventional sessions (2.0 ± 0.65 vs. 2.9 ± 1.21 sessions), average operating time (99.1 ± 34.88 vs. 128.6 ± 72.87 minutes), incidence of intraoperative hemobilia (4.58% vs. 10.93%), cholangitis (6.54% vs. 14.06%), postoperative complications (10.45% vs. 21.87%), T-tube retaining time after first POC (20.7 ± 5.35 vs. 28.1 ± 8.28 days), and treatment costs ($2375 ± 661.72 vs. $3456.7 ± 638.07) were significantly lower in the combined lithotripsy group than those in the EHL group (P < 0.05). There were no differences between the two groups in calculi recurrence at half-a year, or one year follow-up. In conclusion, combined lithotripsy of mechanical clamping and electrohydraulics can safely and effectively benefit postoperative patients along with refractory residual biliary calculi.

4.
J Cell Physiol ; 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32017068

RESUMO

As a polyphenolic compound, resveratrol (Res) is widely present in a variety of plants. Previous studies have shown that Res can inhibit various tumors. However, its role in c remains largely unexplored. In the present study, we first demonstrated that Res inhibited cell viability and induced apoptosis of glioblastoma A172 cell. Further experiments showed that Res induced mitochondrial dysfunction and activated the activity of caspase-9. Functional studies have found that Res treatment is associated with an increase in the expression of Pak2. Interestingly, inhibition of Pak2 could further augment the proapoptotic effect of Res. Mechanistically, Pak2 inhibition induced reactive oxygen species overproduction, mitochondria-JNK pathway activation, and AMPK-YAP axis suppression. However, overexpression of YAP could abolish the anticancer effects of Res and Pak2 inhibition, suggesting a necessary role played by the AMPK-YAP pathway in regulating cancer-suppressive actions of Res and Pak2 inhibition. Altogether, our results indicated that Res in combination with Pak2 inhibition could further enhance the anticancer property of Res and this effect is mediated via the AMPK-YAP pathway.

5.
BMC Plant Biol ; 20(1): 69, 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32046649

RESUMO

BACKGROUND: Acetolactate synthase (ALS)-inhibiting herbicides from the chemical families of sulfonylureas and imidazolinones are used worldwide. However, drift or sprayer contamination from some sulfonylurea herbicides causes a high level of male sterility in cruciferous species, especially oilseed rape (OSR). In this paper, we evaluated the gametocidal effects of 27 ALS-inhibiting herbicides that were sprayed on OSR plants at the bolting stage. RESULTS: OSR anther development was very sensitive to sublethal exposure to most ALS-inhibiting herbicides. The application of 18 out of the 20 tested sulfonylureas (except ethametsulfuron and ethoxysulfuron), two imidazolinones (imazethapyr and imazamox), and one sulfonylamino-carbonyltriazolinone (flucarbazone-sodium) at suitable rates could induce male sterility. Eight of the herbicides, including chlorsulfuron (at application rates of 60-120 mg/ha), halosulfuron-methyl (300-600 mg/ha), sulfosulfuron (400-600 mg/ha), triflusulfuron-methyl (500-750 mg/ha), pyrazosulfuron-ethyl (150-225 mg/ha), nicosulfuron (200-300 mg/ha), imazethapyr (750-1125 mg/ha), and imazamox (400-800 mg/ha), could induce over 90% male sterility and over 60% relative outcrossed seed set in six cultivars with different origins. These eight chemicals could be used as new gametocides for hybrid seed production. This study also examined the possibility of external application of these gametocides on several unstable Polima cytoplasmic male sterile and thermosensitive genic male sterile lines. Although the outcrossed seed set of the treated lines was slightly reduced, the gametocide application significantly increased the seed purity of the resulting hybrid. CONCLUSION: The finding of the gametocidal effects of most sulfonylureas and imidazolinones are of great importance for developing new functions for ALS-inhibiting herbicides. The application of gametocides will also greatly promote the safe utilization of environment-sensitive male sterility in hybrid seed production. Unexpectedly, the application of three triazolopyrimidines (florasulam, flumetsulam, and penoxsulam) and one pyrimidinylthiobenzoate (bispyribac-sodium) did not cause male sterility, although these herbicides obviously inhibited the activity of ALS and plant growth. This result suggests that inhibition of ALS activity does not always lead to male sterility in plants, and these gametocides may also inhibit other biological functions vital for microspore development.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31990059

RESUMO

Aberrant expression of microRNA-876-5p (miR-876-5p) is implicated in the progression of multiple human cancers. However, the potential role of miR-876-5p in colorectal cancer remains poorly understood. The purpose of the current study was to investigate the potential role of miR-876-5p in colorectal cancer. miR-876-5p expression was significantly downregulated in colorectal cancer tissues and cell lines compared with normal controls. Gain-of-function assays revealed that miR-876-5p overexpression effectively repressed the malignant behaviours of colorectal cancer cells, including cell proliferation, colony formation, and invasion. Bioinformatics analysis predicted that RAS protein activator like 2 (RASAL2), a potential oncogene for colorectal cancer, is a putative miR-876-5p target gene. A luciferase reporter assay confirmed that miR-876-5p directly binds to the 3'-untranslated region (UTR) of RASAL2. Furthermore, both RASAL2 messenger RNA (mRNA) and protein expression were negatively modulated by miR-876-5p in colorectal cancer cells. Notably, there was an inverse correlation between miR-876-5p and RASAL2 expression in colorectal cancer tissue specimens. Moreover, miR-876-5p was involved in regulating the activation of Yes-associated protein (YAP) signalling through inhibiting RASAL2. However, the miR-876-5p-mediated antitumour effect on colorectal cancer cells was partially reversed by restoring RASAL2 expression. Notably, miR-876-5p upregulation impeded the tumour growth of colorectal cancer cells in vivo in nude mice. Overall, these results demonstrated that miR-876-5p exerts an antitumour function in colorectal cancer by targeting RASAL2 to suppress YAP signalling activation. These findings highlight the importance of the miR-876-5p/RASAL2/YAP axis in colorectal cancer progression and suggest that miR-876-5p is a potential therapeutic target for treating colorectal cancer.

7.
Artigo em Inglês | MEDLINE | ID: mdl-31981394

RESUMO

Precisely controlled crystal growth endows zeolites with special textural and catalytic properties. A nanosheet mordenite zeolite with a thickness of ca. 11 nm, named as MOR-NS, has been prepared using a well-designed gemini-type amphiphilic surfactant as bifunctional structure-directing agent (SDA). Its benzyl diquarternary ammonium cations structurally directed the formation of MOR topology, whereas the long and hydrophobic hexadecyl tailing group prevented the extensive crystal growth along b axis. This kind of orientated crystallization took place through the inorganic-organic interaction between silica species and SDA molecules present in the whole process. The thin MOR nanosheets, with highly exposed (010) planes and 8-membered ring (MR) windows, exhibited a much improved ethylene selectivity (42.1 %) for methanol-to-olefin (MTO) reactions when compared with conventional bulk MOR crystals (3.3 %).

8.
Thorac Cancer ; 2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31943824

RESUMO

BACKGROUND: This retrospective study compared the efficacy and side effect profile between postoperative adjuvant radiotherapy and chemoradiotherapy in stage II or stage III thoracic esophageal squamous cell carcinoma (TESCC) patients who underwent curative (R0) esophagectomy. METHODS: A total of 272 TESCC patients who underwent radical esophagectomy from 2007 to 2016 were included in this retrospective analysis. All cases were pathologically confirmed with stage II or III disease and 148 patients received postoperative chemoradiotherapy (CRT), while the remaining 124 patients received postoperative radiotherapy (RT) alone. RESULTS: In CRT and RT groups, the three-year overall survival rates were 51.3 versus 31.5% (P < 0.01) and the median overall survival (OS) was 39 months (95% CI, 31.6 to 46.3 months) and 30 months (95% CI, 21.0 to 38.9 months), respectively (P = 0.213). Three-year disease-free survival rates (DFS) were 30.5% versus 15.9% (P = 0.008), while the median DFS times were 26 months (95% CI, 17.7 to 34.3 months) and 19 months (95% CI, 16.4 to 21.6 months), respectively (P = 0.156). Univariate and multivariate analyses showed AJCC (American Joint Committee on Cancer seventh edition) stage and N stage were independent prognostic factors for overall survival, while the N stage was an independent prognostic factor for disease-free survival. CONCLUSIONS: Postoperative chemoradiotherapy led to one- and three-year overall survival benefits along with an obvious increase in treatment side effects for stage II to III TESCC patients, with no further improvement in five-year survival. However, the chemoradiotherapy benefits mainly favor stage III,number of resected lymph nodes less than 15, younger (less than 60 years old) and smoking patients.

9.
J Comp Eff Res ; 9(2): 93-102, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31958984

RESUMO

Aim: To assess the cost-effectiveness of crizotinib verses platinum-based doublet chemotherapy as the first-line treatment for anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC) in the real-world setting. Methods: Data from 163 advanced ALK positive NSCLC patients were collected from West China Hospital, Sichuan University (Chengdu, China). They were categorized into two groups as treated with crizotinib (n = 83) or chemotherapy (n = 80) as a first-line therapy. The progression-free survival (PFS) as the primary clinical outcome, and the direct medical costs were collected from hospital information systems. Incremental cost-effectiveness ratio (ICER) was calculated with costs, quality-adjusted life-years, as well as the costs discounted at 3% annually. Additionally, two different kinds of medical insurance (MI) for pharma-economic assessment were considered. Results: Crizotinib improved PFS versus chemotherapy in ALK positive patients (median PFS 19.67 m vs 5.47 m; p < 0.001). Moreover, crizotinib obtained an ICER of US$36,285.39 before the end of 2016, when crizotinib, pemetrexed and anti-angiogenesis drugs were not MI covered. This is more than the willingness to pay threshold (three-times of gross domestic product per capita in mainland China or Sichuan Province). However, ICER was US$7321.16, which is less than willingness to pay, when crizotinib and all chemotherapy drugs were covered by MI from the end of 2016. Sensitivity analysis demonstrated a 99.7% probability for crizotinib to be more cost-effective than chemotherapy, when crizotinib and all anticancer drugs were MI covered. One-way sensitivity analysis for the reimbursement ratio of crizotinib indicated that cost-effective tendency for crizotinib increased as reimbursement ratio increased. Conclusion: Crizotinib could be an effective, and cost-effective first-line treatment for ALK positive advanced NSCLC with the MI coverage currently available in Chengdu, Sichuan Province, China.

10.
J ECT ; 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31913927

RESUMO

OBJECTIVES: It remains controversial whether a subanesthetic dose of ketamine could modulate the antidepressant effect of electroconvulsive therapy (ECT) in patients with major depressive disorder. We investigated the effect of ketamine on accelerating the antidepressant efficacy of ECT. METHODS: One hundred twenty-seven patients with major depressive disorder were included in this randomized, placebo-controlled, double-blind study. The study group received 0.3 mg/kg ketamine, and the control group received an isovolumetric dose of normal saline before undergoing ECT under propofol anesthesia. The main outcome was the Hamilton Depression Rating Scale score after each ECT session. Suicidal ideation (SI) was also evaluated using the Hamilton Depression Rating Scale. The response, remission, and recurrence rates were analyzed using time-to-event analysis. RESULTS: No significant differences were found in the overall response, remission, and relapse rates between the groups (P > 0.05). The median number of ECT sessions for achieving response was 4.0 ± 0.41 in the study group and 7.0 ± 0.79 in the control group (P < 0.05). The median number of ECT sessions for achieving remission in the study and control groups was 8.0 ± 0.29 and 9.0 ± 0.48, respectively (P < 0.05). The median number of ECT sessions for achieving SI reduction in the study and control groups was 3.0 ± 0.75 and 6.0 ± 1.19, respectively (P < 0.05). CONCLUSIONS: Low-dose ketamine (0.3 mg/kg) could modulate the antidepressant efficacy of ECT via accelerating the onset of its effects and reducing the number of ECT sessions required to obtain response, remission, and SI reduction, without influencing the relapse rates in remitting patients after ECT treatment.

11.
Adv Mater ; 32(3): e1805863, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31216098

RESUMO

Cluster materials have attracted much attention because of their unique chemical and physical properties, hitherto unseen in bulk materials. Inspired by the lipid self-assembly principle, a series of heterocluster Janus molecules (HCJMs) with atomic precision have been rationally designed and synthesized by connecting different clusters via covalent bonds for the construction of nanomaterials and nano-objects. Due to their amphiphilicity, HCJMs self-assemble into cluster-containing nanomaterials or nano-objects with versatile ordered structures beyond those observed in conventional crystals. Their hybrid composition and nanoscale size are also greatly advantageous in the study of their fine structure by electron microscopy techniques, and enable their formation mechanisms to be unraveled. Finally, the influence of the characteristics of the HCJMs on the structure and properties of the self-assembled nano-objects are explored comprehensively. This synthesis strategy will promote further development of cluster materials with advanced functions via rational molecular design toward the construction of hierarchical nanostructures via molecular self-assembly.

12.
J Med Virol ; 92(3): 295-301, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31621089

RESUMO

Human herpesviruses (HHVs) have a particularly high prevalence in certain high-risk populations and cause increased morbidity and mortality in patients with acquired immunodeficiency syndrome (AIDS). Screening and treating subclinical HHV infections reduce human immunodeficiency virus (HIV) infection incidence, disease progression, and transmission. However, there are few studies on HHVs, HIV coinfection rates, and their related risk factors. We aimed to clarify the prevalence of all eight HHVs in peripheral blood samples collected from HIV-positive patients, and explore the association of HHV infection in HIV-positive patients in an HIV-seropositive population in Yunnan. We recruited 121 HIV-positive patients with highly active antiretroviral therapy (HAART) and 45 healthy individuals. All the eight HHVs were detected using polymerase chain reaction and their epidemiological information and clinical data were collected and statistically analyzed. A high prevalence of HHVs (89.3%) was observed in individuals with HIV infections and with herpes simplex virus (HSV)-2 (65.3%), and HSV-1 (59.5%) being the most common. Coinfection with more than two different HHVs was more common in patients with HIV infections receiving HAART (72.7%) than in healthy controls. Older age, being married, higher HIV-1 plasma viral loads, and use of antiviral protease inhibitors were independently correlated with an increased frequency of HHVs, but we found no association with CD4 count, WHO HIV clinical stage, and HIV infection duration. Our findings are of great significance for the prevention of HHV opportunistic infection in patients with AIDS and their clinical treatment.

13.
Chem Commun (Camb) ; 56(4): 651-654, 2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31840151

RESUMO

The direct amination of cyanohydrins with amines via a catalytic cyano-borrowing reaction was developed. The transformation features broad substrate scope, excellent functional group compatibility, and very mild and simple operations. Moreover, a titanium catalyst supported by quinine and (S)-BINOL ligands enabled an asymmetric cyano-borrowing reaction with moderate to high enantioselectivity.

14.
Plant Biotechnol J ; 18(1): 96-105, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31131506

RESUMO

Peanut (Arachis hypogaea. L) is an important oil crop worldwide. The common testa colours of peanut varieties are pink or red. But the peanut varieties with dark purple testa have been focused in recent years due to the potential high levels of anthocyanin, an added nutritional value of antioxidant. However, the genetic mechanism regulating testa colour of peanut is unknown. In this study, we found that the purple testa was decided by the female parent and controlled by a single major gene named AhTc1. To identify the candidate gene controlling peanut purple testa, whole-genome resequencing-based approach (QTL-seq) was applied, and a total of 260.9 Gb of data were generated from the parental and bulked lines. SNP index analysis indicated that AhTc1 located in a 4.7 Mb region in chromosome A10, which was confirmed by bulked segregant RNA sequencing (BSR) analysis in three segregation populations derived from the crosses between pink and purple testa varieties. Allele-specific markers were developed and demonstrated that the marker pTesta1089 was closely linked with purple testa. Further, AhTc1 encoding a R2R3-MYB gene was positional cloned. The expression of AhTc1 was significantly up-regulated in the purple testa parent YH29. Overexpression of AhTc1 in transgenic tobacco plants led to purple colour of leaves, flowers, pods and seeds. In conclusion, AhTc1, encoding a R2R3-MYB transcription factor and conferring peanut purple testa, was identified, which will be useful for peanut molecular breeding selection for cultivars with purple testa colour for potential increased nutritional value to consumers.

15.
Bioorg Med Chem Lett ; 30(1): 126774, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31685339

RESUMO

In continuation of our program to discover new potential antifungal agents, a series of amide and imine derivatives containing a kakuol moiety were synthesized and characterized by the spectroscopic analysis. By using the mycelium growth rate method, the target compounds were evaluated systematically for antifungal activities in vitro against four plant pathogenic fungi, and structure-activity relationships (SAR) were derived. Compounds 7d, 7e, 7h, 7i and 7r showed obvious inhibitory activity against the corresponding tested fungi at 50 µg/mL. Especially, compounds 7e and 7r displayed more potent antifungal activity against B. cinerea than that of thiabendazole (a positive control). Moreover, compound 7e also exhibited good activity against A. alternata with EC50 values of 11.0 µg/mL, and the value was slightly superior to that of thiabendazole (EC50 = 14.9 µg/mL). SAR analysis showed that the ether group was a highly sensitive structural moiety to the activity and the type as well as position of substituents on benzene ring could make some effects on the activity.

16.
J Agric Food Chem ; 68(1): 426-438, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31855429

RESUMO

Modern peanut contains fatty acid desaturase 2 (FAD2) mutation, which is capable of producing high oleic acid for human health. However, the dynamic changes of the lipidome regarding fad2 remain elusive in peanut seed. In the present study, 547 lipid features were identified in high- and normal-oleic peanut seeds by utilizing the mass spectrometric approach. The fad2-induced differently expressed lipids (DELs) were polarly distributed at early and maturation stages during high-oleic acid (OA) seed development. Subsequently, integration of previously published proteomic data and lipidomic data revealed that 21 proteins and 149 DELs were annotated into the triacylglycerol assembly map, of which nine enzymes and 31 lipid species shared similar variation tendencies. Additionally, the variation tendencies of 17 acyl fatty acids were described in a hypothetical biosynthetic pathway. Collectively, the understanding of the lipid composition correlated with fad2 established a foundation for future high-OA peanut breeding based on lipidomic data.


Assuntos
Arachis/química , Lipídeos/química , Ácido Oleico/química , Proteínas de Plantas/química , Arachis/genética , Arachis/crescimento & desenvolvimento , Arachis/metabolismo , Ácidos Graxos Dessaturases/genética , Ácidos Graxos Dessaturases/metabolismo , Metabolismo dos Lipídeos , Mutação , Ácido Oleico/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Proteômica , Sementes/química , Sementes/genética , Sementes/crescimento & desenvolvimento , Sementes/metabolismo
17.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 35(10): 892-896, 2019 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-31814565

RESUMO

Objective To investigate the effect of miR-129-5p on alcohol-induced intestinal epithelial permeability. Methods Real-time quantitative PCR was used to detect the expression level of miR-129-5p in sigmoid colon biopsies and alcohol-induced differentiated Caco-2 cells from patients with alcoholic liver disease and healthy people. Then, the differentiated Caco-2 cells were divided into 4 groups: the control group, the alcohol group (treatment with 50 mmol/L alcohol for 60 minutes), alcohol combined with miR-129-5p inhibitor group (transfection with miR-129-5p inhibitor before alcohol treatment), and alcohol combined with miR-129-5p inhibitor control group (transfection with miR-129-5p inhibitor control before alcohol treatment). After the alcohol treatment, the transepithelial electrical resistance (TER) was analyzed by a resistance meter, and the protein levels relevant to tight junction (occludin and ZO-1) were determined by Western blotting. Results The expression level of miR-129-5p was elevated in the biopsies of the patients with alcoholic liver disease compared with that in the healthy controls. Alcohol treatment increased miR-129-5p expression in the differentiated Caco-2 cells. Compared with the control group, TER and the protein levels of occludin and ZO-1 decreased in the alcohol group. Compared with the alcohol group, TER and the protein levels of occludin and ZO-1 were enhanced in the alcohol combined with miR-129-5p group; however, these changes were not altered in the alcohol combined with miR-129-5p inhibitor control group. Conclusion The miR-129-5p expression is elevated in sigmoid colon biopsies and alcohol-induced differentiated Caco-2 cells from patients with alcoholic liver disease. Inhibition of miR-129-5p can suppress alcohol-induced intestinal epithelial permeability.


Assuntos
Células Epiteliais/efeitos dos fármacos , Etanol/farmacologia , Mucosa Intestinal/citologia , MicroRNAs/genética , Células CACO-2 , Regulação para Baixo , Células Epiteliais/citologia , Humanos , Ocludina/metabolismo , Proteína da Zônula de Oclusão-1/metabolismo
18.
Am J Cancer Res ; 9(11): 2531-2543, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31815051

RESUMO

Cetuximab (C225), an anti-Epidermal Growth Factor receptor (EGFR) monoclonal antibody, has been widely used as a routine treatment for patients with metastatic colorectal cancer (mCRC); However, many patients who initially respond to cetuximab acquire resistance. The purpose of this study was to characterize new mechanism of acquired Cetuximab resistance. Firstly, tissue microarrays (TMA) comprising 191 CRC patients was constructed to evaluate the expression of chemokine receptor 7 (CCR7) by using immunohistochemistry (IHC). In CRC tumor tissues, CCR7 was significantly over-expressed compared with paired normal tissues (P < 0.001), and correlated with the infiltration depth (P = 0.03) and the regional lymph node metastasis (P = 0.006). Significant differences were also found in forms of overall survival (OS) and disease-free survival (DFS) between normal and tumor tissues (P < 0.001). More interestingly, EGFR was also highly expressed and co-localized with CCR7 in the tumor tissues from the patients who were insensitive to Cetuximab treatment. Secondly, we further explored the relationship between CCR7 expression and Cetuximab resistance by two CCR7 positive CRC cell lines, Caco-2 with wild-type KRAS (KRASwt ) and HCT116 with mutated KRAS (KRASG13D ). By the treatment of secondary lymphoid tissue chemokine (SLC, an exogenous high-affinity legend of CCR7), the inhibition rate of Cetuximab significantly decreased in both cells. Furthermore, the activation of SLC/CCR7 axis promoted epithelial mesenchymal transformation (EMT) in CRC tumor cells by increasing the expression of Twist and ß-catenin. By using of CCR7 neutralizing antibody and p-AKT inhibitor rescued the above effects. These findings suggested that CCR7 was a key factor in those CRC patients, who have poorer reaction to Cetuximab. So combined inhibition of CCR7 and p-AKT will represent a rational therapeutic strategy for Cetuximab resistance patients.

19.
Burns ; 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31806262

RESUMO

BACKGROUND: The head and neck regions are frequent sites of burns, but few studies have analysed and reported the epidemiology of facial burns. As the face is the centre of one's identity and persona, facial injuries often result in physical and psychological morbidity. The aim of this article is to describe the epidemiology and outcome of facial burns in China and to suggest future preventive strategies. METHODS: This retrospective analysis included all patients with facial burns in a database at eight institutions from 2011-2015. The data collected included sex, age, month distribution, aetiology, location, presence of inhalation injury, total burn surface area, burn surface area with full-thickness and outcome including Post-traumatic stress disorder Checklist-Civilian Version scores and mortality. SPSS 19.0 software was used to analyse the data. RESULTS: A total of 1126 patients were included; 65.63% (739) had facial burns, of which 546 (73.88%) were male patients and 193 (26.12%) were female patients. Predictors of facial burns were being of male sex, working-related place, flame burns, total body surface area, and full-thickness burns. In addition, total body surface area and full-thickness burns increased the risk of poor prognosis for post-traumatic stress disorder and mortality. CONCLUSIONS: Facial burns benefit not only the healing of wound, but also the prevention of their incidence and PTSD symptom. This study may contribute to the elaboration of strategies to prevent facial burns and the establishment of a nationwide burn database in China.

20.
ACS Cent Sci ; 5(11): 1857-1865, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31807687

RESUMO

Two-dimensional (2D) hybrid perovskite sandwiched between two long-chain organic layers is an emerging class of low-cost semiconductor materials with unique optical properties and improved moisture stability. Unlike conventional semiconductors, ion migration in perovskite is a unique phenomenon possibly responsible for long carrier lifetime, current-voltage hysteresis, and low-frequency giant dielectric response. While there are many studies of ion migration in bulk hybrid perovskite, not much is known for its 2D counterparts, especially for ion migration induced by light excitation. Here, we construct an exfoliated 2D perovskite/carbon nanotube (CNT) heterostructure field effect transistor (FET), not only to demonstrate its potential in photomemory applications, but also to study the light induced ion migration mechanisms. We show that the FET I-V characteristic curve can be regulated by light and shows two opposite trends under different CNT oxygen doping conditions. Our temperature-dependent study indicates that the change in the I-V curve is probably caused by ion redistribution in the 2D hybrid perovskite. The first principle calculation shows the reduction of the migration barrier of I vacancy under light excitation. The device simulation shows that the increase of 2D hybrid perovskite dielectric constant (enabled by the increased ion migration) can change the I-V curve in the trends observed experimentally. Finally, the so synthesized FET shows the multilevel photomemory function. Our work shows that not only we could understand the unique ion migration behavior in 2D hybrid perovskite, it might also be used for many future memory function related applications not realizable in traditional semiconductors.

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