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1.
J Dent ; : 103490, 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-33007363

RESUMO

OBJECTIVES: To evaluate scientific evidence about the impact of implant location on the prevalence of peri-implantitis at implant level. SOURCE: Databases (PubMed, Embase and Cochrane) were searched until March 2020without limitations on language or publication year. Hand searches and gray literature were also included. STUDY SELECTION: Clinical studies reporting data on prevalence of peri-implantitis in anterior and posterior regions at implant level, and evaluations of implants with at least 1 year of function were selected. DATA: Ten studies with a low risk of bias were included. Meta-analysis was performed to estimate the pooled risk ratio. A significantly higher prevalence of peri-implantitis in anterior region compared to posterior region was found (Risk ratio: 1.34; 95% CI: [1.07, 1.69]; p = 0.01). Meta-regression was performed to analyze the potential influence of confounding factors by calculating p-value of the coefficient. Subjects (p = 0.827), implants (p = 0.859) and age (p = 0.656) did not significantly influence the outcome. Subgroup analysis by jaw revealed significantly higher prevalence of peri-implantitis in maxillary anterior (Risk ratio: 1.37; 95% CI: [1.10, 1.71]; p = 0.005) and mandibular anterior (Risk ratio: 1.76; 95% CI: [1.29, 2.42]; p = 0.0004) regions compared to maxillary posterior region. No significant difference was found between maxillary anterior and mandibular posterior (Risk ratio: 1.15; 95% CI: [0.75, 1.75]; p = 0.53) regions. A meta-analysis was precluded between mandibular anterior and mandibular posterior regions due to high statistical heterogeneity (I 2 = 76%). CONCLUSIONS: Implants in the maxillary anterior and mandibular anterior regions had a higher prevalence of peri-implantitis compared to the maxillary posterior region. CLINICAL SIGNIFICANCE: Practitioners should strictly grasp the indications for patients missing anterior teeth and make comprehensive treatment planning.

2.
Dalton Trans ; 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33026381

RESUMO

Two new bifunctional isolated hybrid compounds, [ε-PMoV8MoVI4O37(OH)3Zn4][iql]4·6H2O (1) and [ε-PMoV8MoVI4O38(OH)2Zn4][bipy]3[(CH3COO)(bipy)2Zn]·2H2O (2) (where iql = isoquinoline and bipy = 2,2'-bipyridine), based on Zn-ε-Keggin were successfully synthesized by self-assembly under hydrothermal conditions. It is interesting to note that acetate in 2 acted as a linker connecting the ε-Keggin anion with the one Zn atom (Zn5) and enabled the ε-Keggin anion to coordinate with more bipy ligands, culminating with a larger isolated system, which is the first reported isolated cluster of Zn5PMo12. Meanwhile, compounds 1-2 show great electrochemical behaviors and excellent electrocatalytic activity for the degradation of NaNO2. In addition, compound 2 displays better third-order NLO performance than 1 due to the presence of more conjugated rings, with a TPA cross section (σ) of 1819 GM, which suggests that compound 2 has the potential to function as a bifunctional material with tremendous prospects.

3.
Hum Cell ; 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33047284

RESUMO

This study aimed to investigate the role of long non-coding RNA (lncRNA) taurine up-regulated 1 (TUG1) in the development of ulcerative colitis (UC) and to explore the underlying mechanisms. A murine model of UC was induced by dextran sodium sulfate (DSS) exposure. The colonic epithelial YAMC cells were treated with TNF-α to simulate the inflammatory environment of intestinal epithelial cells (IECs). RNA pull-down and RIP assays were performed to analyze the interaction between TUG1 and HuR. Luciferase activity assay was conducted to evaluate the interaction between TUG1 and miR-29b-3p. Cell proliferation was evaluated by MTT assay. Cell apoptosis was assessed by flow cytometry and western blot analysis of apoptosis-related proteins. TUG1 overexpression promoted cell proliferation and inhibited cell apoptosis in the TNF-α-stimulated YAMC cells. The mechanistic analysis showed that TUG1 positively regulated the HuR/c-myc axis via its interaction with HuR, leading to upregulation of c-myc expression; meanwhile, TUG1 negatively regulated the miR-29b-3p/CDK2 signaling via binding to miR-29b-3p, leading to derepression of CDK2 expression. Further animal experiments showed that TUG1 overexpression attenuated UC progression in the DSS-induced UC in mice. Collectively, TUG1 inhibits IEC apoptosis and UC progression by regulating the balance of HuR and miR-29b-3p.

4.
Stroke ; : STROKEAHA120031479, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33059544

RESUMO

BACKGROUND AND PURPOSE: Brain acidosis is prevalent in stroke and other neurological diseases. Acidosis can have paradoxical injurious and protective effects. The purpose of this study is to determine whether a proton receptor exists in neurons to counteract acidosis-induced injury. METHODS: We analyzed the expression of proton-sensitive GPCRs (G protein-coupled receptors) in the brain, examined acidosis-induced signaling in vitro, and studied neuronal injury using in vitro and in vivo mouse models. RESULTS: GPR68, a proton-sensitive GPCR, was present in both mouse and human brain, and elicited neuroprotection in acidotic and ischemic conditions. GPR68 exhibited wide expression in brain neurons and mediated acidosis-induced PKC (protein kinase C) activation. PKC inhibition exacerbated pH 6-induced neuronal injury in a GPR68-dependent manner. Consistent with its neuroprotective function, GPR68 overexpression alleviated middle cerebral artery occlusion-induced brain injury. CONCLUSIONS: These data expand our knowledge on neuronal acid signaling to include a neuroprotective metabotropic dimension and offer GPR68 as a novel therapeutic target to alleviate neuronal injuries in ischemia and multiple other neurological diseases.

5.
BMC Pulm Med ; 20(1): 266, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33059643

RESUMO

BACKGROUND: Recently, long non-coding RNAs (lncRNAs) have been reported to be involved in regulating chemo-resistance of NSCLC, however, the role of lncRNA SNHG14 in the DDP-resistance of NSCLC remains unexplored. METHODS: Relative expression of SNHG14, HOXB13 and miR-133a in DDP-resistant A549 (A549/DDP) cell and its parental cell A549 were measured using qRT-PCR. Cell proliferation viability of indicated A549/DDP cell was estimated via CCK-8 and colony formation experiments. Cell cycle and apoptosis were analyzed through flow cytometry. Expression of apoptosis-related protein and HOXB13 were detected via western blot. The interaction among SNHG14, HOXB13 and miR-133a was predicted by bioinformatics and validated by dual-luciferase reporter assay. RESULTS: LncRNA SNHG14 and HOXB13 were upregulated while miR-133a was downregulated in A549/DDP cell line compared to A549 cell line. SNHG14 knockdown or miR-133a overexpression was demonstrated to increase the DDP-sensitivity of A549/DDP cells. SNHG14 was revealed to compete with HOXB13 for miR-133a binding in A549/DDP cells. Inhibition of miR-133a in A549 cells could reverse the promotive effects of SNHG14 knockdown on DDP-sensitivity, as well as the inhibitory effects on HOXB13 expression. HOXB13 overexpression was revealed to abolish the enhanced effects of miR-133a on the sensitivity of A549/DDP cell to DDP. CONCLUSION: Our findings demonstrated that SNHG14 was involved in the development of DDP-resistance of A549/DDP cells through miR-133a/HOXB13 axis, which may present a path to novel therapeutic stratagems for DDP resistance of NSCLC.

6.
Anal Chim Acta ; 1134: 75-83, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33059868

RESUMO

Adenosine triphosphate (ATP), as a high-energy phosphate compound that stores and releases energy in living cells, has an irreplaceable role in many physiological processes and maintenance of biological functions, and can be used as an indicator of many diseases. In this work, a composite nanoprobe, silver nanocluster (AgNC) @ molybdenum disulfide (MoS2), was designed to achieve in situ fluorescence imaging and quantitative analysis of intracellular ATP in HeLa cells by fluorescence spectrometry and inductively coupled plasma mass spectrometry (ICP-MS). The probe was constructed based on the adsorption of DNA-AgNCs by MoS2 nanosheets, and the DNA-AgNCs were prepared with the ATP aptamer as a template, whose fluorescence was initially quenched by MoS2. When the probe was incubated into the cells, intracellular ATP recognized the aptamer sequence and caused the DNA-AgNCs to fall off the MoS2 nanosheets, resulting in fluorescence recovery. Here, AgNCs not only acted as a fluorescence label for imaging, but also as an element tag for quantitative analysis of intracellular ATP with the detection of 107Ag by ICP-MS. The ATP in HeLa cells detected by this method was 24.6 ± 1.7 nmol L-1, which was in good agreement with the test result of the ATP test kit (20.4 ± 0.8 nmol L-1). The proposed method has potential application in medical clinical diagnosis and evaluation of the body's metabolic level via fluorescence imaging and ICP-MS detection of intracellular ATP.

7.
Sci Rep ; 10(1): 17486, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33060633

RESUMO

Numb is a negative regulator of Notch signal pathway. Previous study has demonstrated that Notch signal pathway activation is required for hepatic progenitor cell (HPC) differentiating into cholangiocytes in cholestatic liver fibrosis (CLF), and Huang Qi Decoction (HQD) could prevent CLF through inhibition of the Notch signal pathway. However, the role of Numb in HQD against CLF is yet unclear. Thus, CLF rats transplanted into rat bone marrow-derived mesenchymal stem cells with knocked down Numb gene (BMSCNumb-KD) were treated with HQD. Simultaneously, Numb gene knockdown was also performed in WB-F344 cell line and then treated with refined HQD in vitro. In vivo study revealed that liver fibrosis was inhibited by HQD plus BMSCNumb-KD treatment, while Hyp content in liver tissue, the gene and protein expression of α-SMA, gene expression of Col I, TNF-α, and TGF-ß1 were increased compared to that in HQD group. Furthermore, Notch signal pathway was inhibited by HQD plus BMSCNumb-KD, while the protein expression of Numb was decreased and RBP-Jκ and Hes1 was increased compared to that in HQD group. In vitro, HQD reduced the differentiation of WB-F344 cells into cholangiocyte phenotype, while this effect was attenuated after Numb-knockdown. This study highlights that the absence of hepatic stem cell Numb gene decreases effect of HQD against CLF, which give rise the conclusion that Numb might be a potential target for HQD against CLF.

8.
Oral Dis ; 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33031609

RESUMO

OBJECTIVE: Experiments were performed to evaluate CYLD expression in human gingival tissue samples and to examine the effects of CYLD on inflammatory responses in lipopolysaccharide (LPS)- or TNF-α-stimulated human gingival fibroblasts (HGFs). METHODS: Immunohistochemistry for CYLD and p65 expression was performed with healthy and inflamed gingival tissue samples. siRNA was used to knock down the expression of CYLD in HGFs. Upon LPS or TNF-α stimulation, NF-κB activation was detected in control and CYLD-knockdown HGFs. RT-PCR was applied to determine gene expression. Western blot analyses were employed to assess protein expression. Immunofluorescence staining was carried out to evaluate the nuclear translocation of p65. RESULTS: Immunohistochemical staining showed the expression of CYLD in human gingival tissues. In addition, CYLD protein expression was reduced in inflamed gingival tissue samples compared with healthy tissue samples. CYLD knockdown greatly enhanced the mRNA expression of proinflammatory cytokines in LPS- or TNF-α-stimulated HGFs. Furthermore, knocking down CYLD expression increased LPS-stimulated NF-κB activation in HGFs. Unexpectedly, CYLD knockdown did not affect TNF-α-induced NF-κB activation. CONCLUSIONS: Our results suggest that CYLD participates in periodontal inflammatory responses by negatively regulating LPS-induced NF-κB signalling.

9.
Dalton Trans ; 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33034597

RESUMO

Multicomponent spinel ferrites are essential to be used in high-performance gas-sensing materials. Herein, multinary (Cu,Zn)Fe2O4 spinel nano-microspheres with tunable internal structures, including solid, core-shell, and yolk-shell, were successfully synthesized by a simple self-templated solvothermal method combined with a subsequent annealing strategy. The internal structures of the (Cu,Zn)Fe2O4 nano-microspheres significantly rely on the heating rates of the precursors, which show promising selective response towards trimethylamine gas. Among them, the as-formed yolk-shell (Cu,Zn)Fe2O4 nano-microspheres exhibited high response to triethylamine with excellent selectivity of STEA/SX = 1.86 at 160 °C, fast response-recovery rate (58 s/136 s), and long-term repeatability and stability of more than one month. The corresponding triethylamine gas-sensing mechanism with the special microstructures is discussed. This work provides new insights into the rational design of interior structure and the modulation of high gas response and selectivity of multinary spinel ferrites in gas-sensing applications.

10.
Curr Microbiol ; 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33034768

RESUMO

Enteromorpha prolifera (E. prolifera) contains complex sulfated polysaccharides that are resistant to biological degradation. Most organisms cannot digest biomass of E. prolifera, except Siganus oramin (S. oramin). This study was conducted to identify the bacteria in the intestine of S. oramin facilitating the digestion of E. prolifera polysaccharides (EPP). Metagenomic sequencing analysis of the S. oramin intestinal microbiota revealed that E. prolifera diet increased the number of Firmicutes, replacing Proteobacteria to be the dominant bacteria. The proportion of Firmicutes increased from 38.8 to 58.6%, with Bacteroidetes increasing nearly fivefold from 5 to 23.7%. 16S rDNA high-throughput sequencing showed that EPP-induced Bacteroidetes increased significantly in the intestinal flora of S. oramin cultivated in vitro. Metatranscriptome analysis showed that EPP induced more transferase, polysaccharide hydrolase, glycoside hydrolase, and esterases expressed in vitro, and most of them were taxonomically annotated to Bacteroidetes. Compared with the aggregation of GH family genes in metagenomic sequencing analysis in vivo, EPP induced more CBM32, GH2, GT2, GT30, and GH30 families gene expression in vitro. In general, We found that the bacteria in intestinal tract of S. oramin responsible for digestion of E. prolifera were Firmicutes and Bacteroidetes, while Bacteroidetes was the dominant bacteria involved in EPP degradation in vitro cultures. Compared with in vivo experiments, only GH family genes were mostly involved, we detected a more complete and complex EPP degradation pathway in vitro. The results may benefit the further study of biodegradation of E. prolifera and has potential implications for the utilization of E. prolifera for biotechnology.

11.
Theranostics ; 10(25): 11607-11621, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33052236

RESUMO

The hypoxic microenvironment in solid tumors severely limits the efficacy of photodynamic therapy (PDT). Therefore, the development of nanocarriers co-loaded with photosensitizers and oxygen, together with imaging guidance ability, is of great significance in cancer therapy. However, previously reported synthetic methods for these multi-functional probes are complicated, and the raw materials used are toxic. Methods: Herein, the human endogenous protein, hemoglobin (Hb), was used for the simultaneous biomimetic synthesis of Gd-based nanostructures and co-loading of Chlorine e6 (Ce6) and oxygen for alleviating the hypoxic environment of tumors and accomplishing magnetic resonance imaging (MRI)-guided enhanced PDT. The Gd@HbCe6-PEG nanoprobes were synthesized via a green and protein biomimetic approach. The physicochemical properties, including relaxivity, oxygen-carrying/release capability, and PDT efficacy of Gd@HbCe6-PEG, were measured in vitro and in vivo on tumor-bearing mice after intravenous injection. Morphologic and functional MRI were carried out to evaluate the efficacy of PDT. Results: The results demonstrated the successful synthesis of compact Gd@HbCe6-PEG nanostructures with desired multi-functionalities. Following treatment with the nanoparticles, the embedded MR moiety was effective in lighting tumor lesions and guiding therapy. The oxygen-carrying capability of Hb after biomimetic synthesis was confirmed by spectroscopic analysis and oxygen detector in vitro. Further, tumor oxygenation for alleviating tumor hypoxia in vivo after intravenous injection of Gd@HbCe6-PEG was verified by photoacoustic imaging and immunofluorescence staining. The potent treatment efficacy of PDT on early-stage was observed by the morphologic and functional MR imaging. Importantly, rapid renal clearance of the particles was observed after treatment. Conclusion: In this study, by using a human endogenous protein, we demonstrated the biomimetic synthesis of multi-functional nanoprobes for simultaneous tumor oxygenation and imaging-guided enhanced PDT. The therapeutic efficacy could be quantitatively confirmed at 6 h post PDT with diffusion-weighted imaging (DWI).

12.
Int J Clin Pract ; : e13761, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33058366

RESUMO

OBJECTIVE: To explore the effect of comprehensive nursing based on risk prevention in perioperative nursing of intracranial aneurysm. METHODS: A total of 156 patients who suffered from intracranial aneurysm were admitted in neurosurgery department from the hospital between January 2018 and January 2019. Patients were randomly divided into observation group (n = 78, patients were given comprehensive nursing based on risk prevention) and control group (n = 78, patients were given routine nursing). The following parameters, such as postoperative hospital stay, rescue success rate, Glasgow coma scale (GCS) after being awake, anxiety degree and nursing effect (incidence of complications, incidence of infection and patient satisfaction) were compared between the two groups. RESULTS: The postoperative hospital stay, rescue success rate and GCS after intervention in the observation group were significantly better than those in the control group (p < 0.05). The degree of anxiety in the observation group after intervention was superior to that in the control group (p < 0.05), similar results were obtained in terms of the nursing effect in the observation group compared with the control group (p < 0.05). CONCLUSION: Comprehensive nursing was associated with the shortness of hospitalization time of patients, improved rescue rate, reduced occurrence of complications and infection, and improved satisfaction of patients. Thus, comprehensive nursing was regarded to exert protective effect with a promising future for clinical practice.

13.
Medicine (Baltimore) ; 99(40): e22572, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019469

RESUMO

RATIONALE: Atorvastatin is the most common drug used in therapy for cardiovascular diseases. The most common adverse side effects associated with statins are myopathy and hypertransaminasemia. Here, we report a rare case of gamma glutamyl transpeptidase (GGT) elevation induced by atorvastatin. PATIENT CONCERNS: A 47-year-old male was admitted to our hospital with dyslipidemia, he had been taking pitavastatin 2 mg/day for 2 months. The levels of total cholesterol (265.28 mg/dL) and low-density lipoprotein-cholesterol (LDL) (179.15 mg/dL) were also high. DIAGNOSIS: Blood lipid test showed mixed dyslipidemia. INTERVENTION: Atorvastatin 10 mg/day was given to the patient. OUTCOMES: The patient came back to our hospital for blood tests after 4 weeks. Although no symptoms were detectable, the patient's GGT level was markedly elevated (up to 6-fold over normal level) with less marked increases in alkaline phosphatase (ALP) and alanine aminotransferase (ALT). The serum GGT level returned to normal within 6 weeks of cessation of atorvastatin. LESSONS: This is a case of GGT elevation without hyperbilirubinemia, hypertransaminasemiam, or serum creatine phosphokinase (CPK) abnormalities despite an atorvastatin regimen. This case highlights GGT elevation caused by atorvastatin, a rare but serious condition. Clinicians should be aware of these possible adverse effects and monitor liver function tests in patients on statin therapy.


Assuntos
Atorvastatina/efeitos adversos , Dislipidemias/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Quinolinas/efeitos adversos , gama-Glutamiltransferase/efeitos dos fármacos , Alanina Transaminase/sangue , Fosfatase Alcalina/sangue , Atorvastatina/administração & dosagem , Atorvastatina/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Dislipidemias/diagnóstico , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Quinolinas/administração & dosagem , Quinolinas/uso terapêutico , Suspensão de Tratamento , gama-Glutamiltransferase/sangue
14.
J Aerosol Sci ; : 105693, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33078030

RESUMO

The COVID-19 pandemic has brought an unprecedented crisis to the global health sector. When discharging COVID-19 patients in accordance with throat or nasal swab protocols using RT-PCR, the potential risk of reintroducing the infection source to humans and the environment must be resolved. Here, 14 patients including 10 COVID-19 subjects were recruited; exhaled breath condensate (EBC), air samples and surface swabs were collected and analyzed for SARS-CoV-2 using reverse transcription-polymerase chain reaction (RT-PCR) in four hospitals with applied natural ventilation and disinfection practices in Wuhan. Here we discovered that 22.2% of COVID-19 patients (n = 9), who were ready for hospital discharge based on current guidelines, had SARS-CoV-2 in their exhaled breath (~105 RNA copies/m3). Although fewer surface swabs (3.1%, n = 318) tested positive, medical equipment such as face shield frequently contacted/used by healthcare workers and the work shift floor were contaminated by SARS-CoV-2 (3-8 viruses/cm2). Three of the air samples (n = 44) including those collected using a robot-assisted sampler were detected positive by a digital PCR with a concentration level of 9-219 viruses/m3. RT-PCR diagnosis using throat swab specimens had a failure rate of more than 22% in safely discharging COVID-19 patients who were otherwise still exhaling the SARS-CoV-2 by a rate of estimated ~1400 RNA copies per minute into the air. Direct surface contact might not represent a major transmission route, and lower positive rate of air sample (6.8%) was likely due to natural ventilation (1.6-3.3 m/s) and regular disinfection practices. While there is a critical need for strengthening hospital discharge standards in preventing re-emergence of COVID-19 spread, use of breath sample as a supplement specimen could further guard the hospital discharge to ensure the safety of the public and minimize the pandemic re-emergence risk.

15.
J Cell Physiol ; 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33078404

RESUMO

Lung cancer is the leading cause of cancer-related deaths worldwide, in which angiogenesis is highly required for lung cancer cell growth and metastasis. Genetic regulation of this multistep process is being studied extensively, however, relatively less is known about the epigenetic regulation of angiogenesis in lung cancer. Several epigenetic alterations contribute to regulating angiogenesis, such as epimodifications of DNA, posttranslational modification of histones, and expression of noncoding RNAs. Here, we review the current knowledge of the epigenetic regulation of angiogenesis and discuss the potential clinical applications of epigenetic-based anticancer therapy in lung cancer. Overall, epigenetic-based therapy will likely emerge as a prominent approach to treat lung cancer in the future.

16.
Immunol Invest ; : 1-14, 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-33078652

RESUMO

Background: Influenza A viruses (IAVs) induce acute respiratory disease and cause severe epidemics and pandemics. Since IAVs exhibit antigenic variation and genome reassortment, the development of broad-spectrum influenza vaccines is crucial. The stem of the hemagglutinin (HA) is highly conserved across IAV strains and thus has been explored in broad-spectrum influenza vaccine studies. The present study aimed to identify viral epitopes capable of eliciting effective host immune responses, which can be explored for the development of broad-spectrum non-strain specific prophylactic options against IAV. Methods: In this study, a series of conserved linear sequences from the HA stem of IAV (H1N1) was recognized by sequence alignment and B/T-cell epitope prediction after being chemically coupled to the Keyhole Limpet Hemocyanin (KLH) protein. The predicted linear epitopes were identified by enzyme-linked immunosorbent assay (ELISA) after animal immunization and then fused with ferritin carriers. Results: Three predicted linear epitopes with relatively strong immunogenicity, P3, P6 and P8 were fused with ferritin carriers P3F, P6F and P8F, respectively to further improve their immunogenicity. Antibody titre of the sera of mice immunized with the recombinant immunogens revealed the elicitation of specific antibody-binding activities by the identified sequences. While hemagglutinin-inhibition activities were not detected in the antisera, neutralizing antibodies against the H1 and H3 virus subtypes were detected by the microneutralization assay. Conclusion: The linear epitopes fused with ferritin identified in this study can lay the foundation for future advancements in development of broad-spectrum subunit vaccine against IAV (H1N1), and give rise to the potential future applicability of ferritin-based antigen delivery nanoplatforms.

17.
Environ Pollut ; 268(Pt B): 115362, 2020 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-33035873

RESUMO

The emergence of clinically relevant ß-lactam-resistant bacteria poses a serious threat to human health and presents a major challenge for medical treatment. How opportunistic pathogenic bacteria acquire antibiotic resistance and the prevalence of antibiotic-resistant opportunistic pathogenic bacteria in the environment are still unclear. In this study, we further confirmed that the selective pressure of heavy metals contributes to the increase in ampicillin-resistant opportunistic pathogens in the Xiangjiang River. Four ampicillin-resistant opportunistic pathogenic bacteria (Pseudomonas monteilii, Aeromonas hydrophila, Acinetobacter baumannii, and Staphylococcus epidermidis) were isolated on Luria-Bertani (LB) agar plates and identified by 16S rRNA sequencing. The abundance of these opportunistic pathogenic bacteria significantly increased in the sites downstream of the Xiangjiang River that were heavily influenced by metal mining activities. A microcosm experiment showed that the abundance of ß-lactam resistance genes carried by opportunistic pathogenic bacteria in the heavy metal (Cu2+ and Zn2+) treatment group was 2-10 times higher than that in the control. Moreover, heavy metals (Cu2+ and Zn2+) significantly increased the horizontal transfer of plasmids in pathogenic bacteria. Of particular interest is that heavy metals facilitated the horizontal transfer of conjugative plasmids, which may lead to the prevalence of multidrug-resistant pathogenic bacteria in the Xiangjiang River.

18.
J Thromb Haemost ; 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33075181

RESUMO

BACKGROUND: Von Willebrand Factor (VWF) contains a number of free thiols, the majority of which are located in its C-domains, and these have been shown to alter VWF function, However, the impact of free-thiols on function following acute exposure of VWF to collagen under high and pathological shear stress has not been determined. METHODS: VWF free-thiols were blocked with N-ethylmaleimide (NEM) and flow assays performed under high and pathological shear rates to determine the impact on platelet capture and collagen binding function. Atomic force microscopy (AFM) was used to probe the interaction of VWF with collagen and molecular simulations conducted to determine the effect of free-thiols on the flexibility of the VWF-C4 domain. RESULTS: Blockade of VWF free-thiols reduced VWF mediated platelet capture to collagen in a shear dependent manner, with platelet capture virtually abolished above 5000s-1 and in regions of stenosis in microfluidic channels. Direct visualisation of VWF fibres formed under extreme pathological shear rates and analysis of collagen bound VWF attributed the effect to altered binding of VWF to collagen. AFM measurements showed that thiol-blockade reduced the life-time and strength of the VWF-collagen bond. Pulling simulations of the VWF-C4 domain demonstrated that with one or two reduced disulphide bonds the C4 domain has increased flexibility and the propensity to undergo free-thiol exchange. CONCLUSIONS: We conclude that free-thiols in the C-domains of VWF enhance the flexibility of the molecule and enable it to withstand high shear forces following collagen binding, demonstrating a previously unrecognised role for VWF free-thiols.

19.
Aging (Albany NY) ; 122020 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-33040049

RESUMO

OBJECTIVE: This study aims to explore the roles of miR-124 in pancreatic tumor and potential vehicles. RESULTS: The miR-124 expression levels decreased in pancreatic adenocarcinoma tissues and cancer cell lines AsPC-1, PANC1, BxPC-3 and SW1990. Furthermore, the elevated expression of miR-124 in AsPC-1 and PANC1 via miR-124 mimic transfection-induced apoptosis, metastasis and epithelial mesenchymal transition was suppressed, and the EZH2 overexpression partly reversed the protective effects of miR-124 against pancreatic tumors. In addition, the expression of miR-124 was detected in exosomes extracted from miR-124-transfected BM-MSCs, and these exosomes delivered miR-124 into pancreatic cancer cells, and presented the anti-tumor effects in vitro and in vivo. CONCLUSION: MiR-124-carried BM-MSC-derived exosomes have potential applications for the treatment of pancreatic tumors. METHODS: The expression of miR-124 and EZH2 was determined in both pancreatic cancer tissues and cell lines. miR-124 or EZH2 was overexpressed in AsPC-1 and PANC1 cells. Then, the effects on cell viability. apoptosis, invasion, migration and epithelial mesenchymal transition were evaluated. Afterwards, the roles of miR-124 on the expression and function of EZH2 in pancreatic tumors were determined by dual luciferase reporter assay. Subsequently, miR-124 was transfected to bone marrow mesenchymal stromal cells (BM-MSCs), and the BM-MSCs derived exosomes were isolated and co-cultured with AsPC-1 and PANC1 cells, or injected into pancreatic cancer tumor-bearing mice.

20.
Cell Biol Toxicol ; 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-33040242

RESUMO

Cadmium (Cd), a highly toxic heavy metal, is widespreadly distributed in the environment. Chronic exposure to Cd is associated with the development of several diseases including cancers. Over the decade, many researches have been carried on various models to examine the acute effects of Cd; yet, limited knowledge is known about the long-term Cd exposure, especially in the human lung cells. Previously, we showed that chronic Cd-exposed human bronchial epithelial BEAS-2B cells exhibited transformed cell properties, such as anchorage-independent growth, augmented cell migration, and epithelial-mesenchymal transition (EMT). To study these Cd-transformed cells more comprehensively, here, we further characterized their subproteomes. Overall, a total of 63 differentially expressed proteins between Cd-transformed and passage-matched control cells among the five subcellular fractions (cytoplasmic, membrane, nuclear-soluble, chromatin-bound, and cytoskeletal) were identified by mass spectrometric analysis and database searching. Interestingly, we found that the thiol protease ubiquitin carboxyl-terminal hydrolase isozyme L1 (UCHL1) is one of the severely downregulated proteins in the Cd-transformed cells. Notably, the EMT phenotype of Cd-transformed cells can be suppressed by forced ectopic expression of UCHL1, suggesting UCHL1 as a crucial modulator in the maintenance of the proper differentiation status in lung epithelial cells. Since EMT is considered as a critical step during malignant cell transformation, finding novel cellular targets that can antagonize this transition may lead to more efficient strategies to inhibit cancer development. Our data report for the first time that UCHL1 may play a function in the suppression of EMT in Cd-transformed human lung epithelial cells, indicating that UCHL1 might be a new therapeutic target for chronic Cd-induced carcinogenesis. Graphical abstract.

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