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1.
Methods Mol Biol ; 2147: 125-135, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32840815

RESUMO

Nano- and micro-scaled fibers have been incorporated in a number of applications in biofabrication and tissue cultures, providing a cell interfacing structure with extracellular matrix-mimicking topography and adhesion sites, and further supporting localized drug release. Here, we describe the low-voltage electrospinning patterning (LEP) protocol, which allows direct and continuous patterning of sub-micron fibers in a controlled fashion. The processable polymers range from protein (e.g., gelatin) to thermoplastic (e.g., polystyrene) polymers, with flexible selections of collecting substrates. The operation voltage for fiber fabrication can be as low as 50 V, which brings the benefits of reducing costs and mild-processing.

2.
Sci Adv ; 6(40)2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32998891

RESUMO

Scalability and device integration have been prevailing issues limiting our ability in harnessing the potential of small-diameter conducting fibers. We report inflight fiber printing (iFP), a one-step process that integrates conducting fiber production and fiber-to-circuit connection. Inorganic (silver) or organic {PEDOT:PSS [poly(3,4-ethylenedioxythiophene) polystyrene sulfonate]} fibers with 1- to 3-µm diameters are fabricated, with the fiber arrays exhibiting more than 95% transmittance (350 to 750 nm). The high surface area-to-volume ratio, permissiveness, and transparency of the fiber arrays were exploited to construct sensing and optoelectronic architectures. We show the PEDOT:PSS fibers as a cell-interfaced impedimetric sensor, a three-dimensional (3D) moisture flow sensor, and noncontact, wearable/portable respiratory sensors. The capability to design suspended fibers, networks of homo cross-junctions and hetero cross-junctions, and coupling iFP fibers with 3D-printed parts paves the way to additive manufacturing of fiber-based 3D devices with multilatitude functions and superior spatiotemporal resolution, beyond conventional film-based device architectures.

3.
Mol Neurobiol ; 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33025508

RESUMO

Nod-like receptor protein 3 (NLRP3)-associated neuroinflammation mediated by activated microglia is involved in the pathogenesis of depression. The role of the pore-forming protein gasdermin D (GSDMD), a newly identified pyroptosis executioner downstream of NLRP3 inflammasome mediating inflammatory programmed cell death, in depression has not been well defined. Here, we provide evidence that paeoniflorin (PF), a monoterpene glycoside compound derived from Paeonia lactiflora, ameliorated reserpine-induced mouse depression-like behaviors, characterized as increased mobility time in tail suspension test and forced swimming test, as well as the abnormal alteration of synaptic plasticity in the depressive hippocampus. The molecular docking simulation predicted that PF would interact with C-terminus of GSDMD. We further demonstrated that PF administration inhibited the enhanced expression of GSDMD which mainly distributed in microglia, along with the proteins involved in pyroptosis signaling transduction including caspase (CASP)-11, CASP-1, NLRP3, and interleukin (IL)-1ß in the hippocampus of mice treated with reserpine. And also, PF prevented lipopolysaccharide (LPS) and adenosine triphosphate (ATP)-induced pyroptosis in murine N9 microglia in vitro, evidenced by inhibiting the expression of CASP-11, NLRP3, CASP-1 cleavage, as well as IL-1ß. Furthermore, VX-765, an effective and selective inhibitor for CASP-1 activation, reduced the expression of inflammasome and pyroptosis-associated proteins in over-activated N9 and also facilitated PF-mediated inhibition of pyroptosis synergistically. Collectively, the data indicated that PF exerted antidepressant effects, alleviating neuroinflammation through inhibiting CASP-11-dependent pyroptosis signaling transduction induced by over-activated microglia in the hippocampus of mice treated with reserpine. Thus, GSDMD-mediated pyroptosis in activated microglia is a previously unrecognized inflammatory mechanism of depression and represents a unique therapeutic opportunity for mitigating depression given PF administration.

4.
Cancer Commun (Lond) ; 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33017522

RESUMO

BACKGROUND: Dopamine and dopamine receptor D1 (DRD1), a member of the dopamine receptor family, have been indicated to play important roles in cancer progression, but dopamine secretion in hepatocellular carcinoma (HCC) and the effects of DRD1 on HCC remain unclear. This study was designed to explore the contribution of the dopaminergic system to HCC and determine the relationship between DRD1 and prognosis in HCC patients. METHODS: The dopamine metabolic system was monitored using enzyme-linked immunosorbent assays (ELISAs). The expression of DRD1 was detected by microarray analysis, immunohistochemistry (IHC), and quantitative real-time PCR (qRT-PCR). Stable DRD1 knockout and overexpression cell lines were established for investigation. Transwell, colony formation, and Cell Counting Kit 8 (CCK8) assays were performed to assess the malignant behaviors of cancer cells. The cAMP/PI3K/AKT/ cAMP response element-binding (CREB) signaling pathway was evaluated by Western blot. This pathway, which is agitated by DRD1 in striatal neurons, had been proven to participate in tumor progression. Xenograft HCC tumors were generated for in vivo experiments. RESULTS: Dopamine secretion increased locally in HCC due to an imbalance in dopamine metabolism, including the upregulation of dopa decarboxylase (DDC) and the downregulation of monoamine oxidase A (MAOA). Dopamine promoted the proliferation and metastasis of HCC. DRD1 was highly expressed in HCC tissues and positive DRD1 expression was related to a poor prognosis in HCC patients. The upregulation of DRD1 agitated malignant activities, including proliferation and metastasis in HCC by regulating the cAMP/PI3K/AKT/CREB pathway, and the downregulation of DRD1 had opposing effects. The effects of dopamine on HCC was reversed by depleting DRD1. SCH23390, a selective DRD1 antagonist, inhibited the proliferation and metastasis of HCC cells both in vitro and in vivo. CONCLUSION: Dopamine secretion was locally increased in HCC and promoted HCC cell proliferation and metastasis. DRD1 was found to exert positive effects on HCC progression and play a vital role in the dopamine system, and could be a potential therapeutic target and prognostic biomarker for HCC.

5.
Oncol Rep ; 44(5): 2080-2092, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33000261

RESUMO

Emerging studies have demonstrated that long non­coding RNAs (lncRNAs) play essential roles in tumorigenesis. However, the role and function of lncRNAs in hypopharyngeal squamous cell carcinoma (HSCC) have not been completely elucidated. The present study explored the function of a novel lncRNA, RP11­156L14.1, in HSCC. RP11­156L14.1 was revealed to be highly expressed in HSCC tissues and cell lines. Knockdown of RP11­156L14.1 inhibited proliferation, migration, and invasion in HSCC cells. Furthermore, RP11­156L14.1 regulated epithelial­mesenchymal transition (EMT) by controlling EMT­related protein expression. Mechanistically, RP11­156L14.1 exerted its function as a competing endogenous RNA (ceRNA) and directly interacted with miR­548ao­3p. The present study also demonstrated that miR­548ao­3p regulated signal sequence receptor subunit 1 (SSR1) expression by targeting SSR1 3'­UTR. Moreover, the xenograft HSCC tumor model revealed that knockdown of RP11­156L14.1 markedly suppressed HSCC tumor growth in vivo. In summary, these findings indicated that the lncRNA RP11­156L14.1 functions as an oncogene in HSCC by competing with miR­548ao­3p in regulating SSR1 expression. The RP11­156L14.1/miR­548ao­3p/SSR1 axis could be utilized as a potential novel biomarker and therapeutic target for HSCC.

6.
J Biomed Opt ; 25(10)2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33029991

RESUMO

SIGNIFICANCE: Photoacoustic imaging (PAI) has been greatly developed in a broad range of diagnostic applications. The efficiency of light to sound conversion in PAI is limited by the ubiquitous noise arising from the tissue background, leading to a low signal-to-noise ratio (SNR), and thus a poor quality of images. Frame averaging has been widely used to reduce the noise; however, it compromises the temporal resolution of PAI. AIM: We propose an approach for photoacoustic (PA) signal denoising based on a combination of low-pass filtering and sparse coding (LPFSC). APPROACH: LPFSC method is based on the fact that PA signal can be modeled as the sum of low frequency and sparse components, which allows for the reduction of noise levels using a hybrid alternating direction method of multipliers in an optimization process. RESULTS: LPFSC method was evaluated using in-silico and experimental phantoms. The results show a 26% improvement in the peak SNR of PA signal compared to the averaging method for in-silico data. On average, LPFSC method offers a 63% improvement in the image contrast-to-noise ratio and a 33% improvement in the structural similarity index compared to the averaging method for objects located at three different depths, ranging from 10 to 20 mm, in a porcine tissue phantom. CONCLUSIONS: The proposed method is an effective tool for PA signal denoising, whereas it ultimately improves the quality of reconstructed images, especially at higher depths, without limiting the image acquisition speed.

7.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 2342-2345, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33018477

RESUMO

Resistant hypertension (RH) is a major healthcare issue, causing cardiovascular and cerebrovascular diseases. In recent years, radiofrequency (RF) ablation to renal sympathetic denervation (RSD) is a new effective method for the treatment of RH. However, the effect of RSD on renal artery blood flow still need further research. In this study, Particle Image Velocimetry (PIV) experiment and RF ablation experiment were used to observe the blood flow states in three conditions: no ablation with flow, ablation with no flow, and ablation with flow. The results showed that when the blood flow was 1L/min in renal artery without ablation, it was uniform laminar flow. When the blood was static in renal artery with ablation, there was eddy around the ablation catheter. When the blood flow was 1L/min in renal artery with ablation, the eddy disappeared and the blood flow was uniform laminar flow. Therefore, when the renal artery blood flow is 1L/min, there will be no thrombus and hemolysis in the renal artery due to eddy current and large velocity gradient, which preliminarily verified the safety of the RSD. Keyword: Resistant hypertension; Radiofrequency ablation; Flow field; PIVClinical relevance-When the blood flow of renal artery is 1L/min, there will be no thrombus and hemolysis in renal artery due to eddy current and large velocity gradient during the operation of RF ablation to renal sympathetic denervation.

8.
Clin Interv Aging ; 15: 1831-1839, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33061333

RESUMO

Objective: Early-onset dementia (EOD) is a relatively uncommon form of dementia that afflicts people before age 65. Only a few studies analyzing the genetics of EOD have been performed in the Chinese Han population. Diagnosing EOD remains a challenge due to the diverse genetic and clinical heterogeneity of these diseases. The aim of this study was to investigate the genetic spectrum and clinical features of Chinese patients with EOD. Materials and Methods: A total of 49 EOD patients were recruited. Targeted next-generation (NGS) analyses were performed to screen for all of the known genes associated with dementia. Possible pathogenic variants were confirmed by performing Sanger sequencing. The genetic spectrum and clinical features of the EOD patients were analyzed. Results: Seven previously reported pathogenic variants (p.I213T and p.W165C in PSEN1; p.D678N in APP; c.1349_1352del in TBK1; p.P301L and p.R406W in MAPT; p.R110C in NOTCH3) and two novel variants of uncertain significance (p.P436L in PSEN2; c.239-11G>A in TARDBP) were identified. Conclusion: Our study demonstrated the genetic spectrum and clinical features of EOD patients, and it reveals that genetic testing of known causal genes in EOD patients can help to make a precise diagnosis.

9.
ACS Synth Biol ; 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33048520

RESUMO

Komagataeibacter xylinus has received increasing attention as an important microorganism for the conversion of several carbon sources to bacterial cellulose (BC). However, BC productivity has been impeded by the lack of efficient genetic engineering techniques. In this study, a lambda Red and FLP/FRT-mediated site-specific recombination system was successfully established in Komagataeibacter xylinus. Using this system, the membrane bound gene gcd, a gene that encodes glucose dehydrogenase, was knocked out to reduce the modification of glucose to gluconic acid. The engineered strain could not produce any gluconic acid and presented a decreased bacterial cellulose (BC) production due to its restricted glucose utilization. To address this problem, the gene of glucose facilitator protein (glf; ZMO0366) was introduced into the knockout strain coupled with the overexpression of the endogenous glucokinase gene (glk). The BC yield of the resultant strain increased by 63.63-173.68%, thus reducing the production cost.

10.
J Health Commun ; : 1-10, 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33048635

RESUMO

To examine the feasibility and acceptability of an interactive video program of African American breast cancer survivor stories, we explored story reactions among African American women with newly diagnosed breast cancer and associations between patient factors and intervention use. During a randomized controlled trial, patients in the intervention arm completed a baseline/pre-intervention interview, received the video intervention, and completed a post-intervention 1-month follow-up interview. Additional video exposures and post-exposure interviews occurred at 6- and 12-month follow-ups. Multivariable linear mixed-effects models examined interview and clinical data in association with changes in minutes and actions using the program. After Exposure1, 104 of 108 patients allocated to the intervention reported moderate-to-high levels of positive emotional reactions to stories and identification with storytellers. Exposure1 mean usage was high (139 minutes) but declined over time (p <.0001). Patients receiving surgery plus radiation logged about 50 more minutes and actions over 12-month follow-up than patients receiving surgery only (p <.05); patients reporting greater trust in storytellers logged 18.6 fewer actions over time (p =.04). Patients' topical interests evolved, with patients watching more follow-up care and survivorship videos at Exposure3. The intervention was feasible and evaluated favorably. New videos might satisfy patients' changing interests.

11.
Zootaxa ; 4801(3): zootaxa.4801.3.9, 2020 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-33056650

RESUMO

In this work, one new species Microtachycines trispinosus Qin et Li sp. nov. from Sanqingshan of Jiangxi province is described and illustrated with photographs. It is mentioned that Microtachycines fallax Qin, Liu, Li, 2017 should be regarded as the junior synonym of Microtachycines elongatus Qin, Liu Li, 2017. All examined specimens are deposited in Shanghai Entomological Museum, Chinese Academy of Sciences (SEM, CAS).

12.
BMC Geriatr ; 20(1): 414, 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33076841

RESUMO

BACKGROUND: Frailty is now seen as a significant factor in older people with diabetes, whose mortality and disability increased. This study aims to investigate the association between calf circumference (CC) with frailty in diabetic adults aged over 80 years. METHODS: A cross-sectional analysis was performed on the data of 426 diabetic adults aged over 80 years. On admission, demographic data and laboratory parameters were recorded. CC was measured on the lower right leg at the point of the maximal circumference. All participants accepted frailty assessments. Frailty was mainly defined using the Fried frailty phenotype criteria. RESULTS: The CC levels were significantly lower in the frail than the non-frail (26.7 ± 4.0 vs. 31.2 ± 4.0, P < 0.001). CC was negatively correlated with the Fried frailty phenotype index (P < 0.001). Logistic regression analysis of frailty revealed that age (Odds Ratio (OR), 1.368; 95% Confidential Interval (CI) 1.002-1.869; P = 0.049), CC (OR, 0.756; 95%CI 0.598-0.956; P = 0.019) were independent impact factors of frailty after adjusting all the potential confounders. Participants with low CC tertile had a significantly higher Fried frailty phenotype index than those with high CC tertiles. The best CC cut-off value for predicting frailty was 29.3 cm, its sensitivity was 75.0%, and the specificity was 78.6%, and areas under the curve (AUC) was 0.786 (P < 0.001). CONCLUSIONS: CC was strongly related to frailty in diabetic adults aged over 80 years, suggesting that CC may be helpful for monitoring physical frailty in older adults in clinical and research settings.

13.
Addict Behav ; 113: 106677, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-33069106

RESUMO

INTRODUCTION: Mindfulness training (MT) has shown preliminary efficacy as a behavioral treatment for smoking cessation. We examined the effect of a brief-MT intervention on smoking cessation for Chinese women in workplaces in Hong Kong, China. METHODS: In this pilot randomized controlled trial, 213 daily smokers were recruited from workplaces and computer-randomized into the intervention (n = 114) or control (n = 99) groups. Participants in both groups received a self-help booklet. Participants in the intervention group additionally attended 2 sessions of a brief-MT workshop. The primary outcome was self-reported 7-day point-prevalence abstinence (PPA) at 6 months. Secondary outcomes were biochemically validated abstinence (exhaled CO < 4 ppm and salivary cotinine < 10 ng/mL) and smoking reduction at 6 months. Analyses were done by intention to treat. We conducted a post-trial qualitative evaluation on participants in the intervention group (n = 14). Data were analyzed thematically. RESULTS: At 6-month follow-up, self-reported 7-day PPA were similar between the intervention and control groups (18.4% vs. 21.2%; P = 0.61). Very few participated in biochemical validation (n = 17), and validated abstinence and smoking reduction rates showed no significant difference (5.3% vs. 11.1%, P = 0.12 and 20.2% vs. 20.2%, P = 1.00, respectively). A posteriori analysis showed that brief-MT participants who were psychologically engaged with the intervention had greater 6-month PPA. Qualitative evaluation showed brief-MT reduced stress but its effectiveness was restrained by the insufficient home practice. CONCLUSIONS: This pilot trial on a brief-MT intervention for smoking cessation on Chinese women in workplaces showed feasibility, but improving compliance is needed to maximize the efficacy in future fully powered trials.

14.
Artigo em Inglês | MEDLINE | ID: mdl-33036443

RESUMO

Evidence suggests that excessive screen time in early childhood is related to children's physical and mental health. This study aimed to review the relationships between screen media use and several health indicators in infants, toddlers, and preschoolers. A systematic search was conducted by two independent reviewers on PubMed, Web of Science, Embase, and Cochrane Library to identify the eligible studies, with an end date of 13 August 2019. Included studies (published in English) were peer-reviewed and met the determinate population (children aged 0-7 years with screen media exposure and related health outcomes). The AHRQ, NOS, and the Cochrane Handbook were used to evaluate the cross-sectional study, cohort study, and RCT, respectively. A meta-analysis and narrative syntheses were employed separately. Eighty studies (23 studies for meta-analysis) met the inclusion criteria for the systematic review. Strong evidence of the meta-analysis suggested that excessive screen time was associated with overweight/obesity and shorter sleep duration among toddlers and preschoolers. Excessive screen use was associated with various health indicators in physical, behavioral, and psychosocial aspects. Better-quality research on newer media devices, on various kinds of contents in young children, and on dose-response relationships between excessive screen use and health indicators are needed to update recommendations of screen use.

15.
Autophagy ; : 1-22, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33044112

RESUMO

Accumulation of toxic protein assemblies and damaged mitochondria are key features of neurodegenerative diseases, which arise in large part from clearance defects in the Macroautophagy/autophagy-lysosome system. The autophagy cargo receptor SQSTM1/p62 plays a major role in the clearance of ubiquitinated cargo through Ser403 phosphorylation by multiple kinases. However, no phosphatase is known to physiologically dephosphorylate SQSTM1 on this activating residue. RNAi-mediated knockdown and overexpression experiments using genetically encoded fluorescent reporters and defined mutant constructs in cell lines, primary neurons, and brains show that SSH1, the canonical CFL (cofilin) phosphatase, mediates the dephosphorylation of phospho-Ser403-SQSTM1, thereby impairing SQSTM1 flux and phospho-MAPT/tau clearance. The inhibitory action of SSH1 on SQSTM1 is fully dependent on SQSTM1 Ser403 phosphorylation status and is separable from SSH1-mediated CFL activation. These findings reveal a unique action of SSH1 on SQSTM1 independent of CFL and implicate an inhibitory role of SSH1 in SQSTM1-mediated clearance of autophagic cargo, including phospho-MAPT/tau. Abbreviations: AAV: adeno-associated virus; Aß42O: amyloid ß1-42 oligomers; AD: Alzheimer disease; CA3: cornu Ammonis 3; CSNK2/CK2: casein kinase 2; FCCP: 2-[2-[4-(trifluoromethoxy)phenyl]hydrazinylidene]-propanedinitrile; FTLD: frontotemporal lobar degeneration; GFP: green fluorescent protein; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; SQSTM1/p62: sequestosome-1; PLA: proximity ligation assay; RFP: red fluorescent protein; RIPA: radioimmunoprecipitation assay; shRNA: short hairpin RNA; siRNA: small interfering RNA; Ser403: Serine403; SSH1: slingshot protein phosphatase 1; TBK1: TANK-binding kinase 1; ULK: unc-51 like kinase 1.

16.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(5): 1699-1703, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33067977

RESUMO

OBJECTIVE: To investigate the diagnostic value of thromboelastography(TEG) for acute disseminated intravascular coagulation(DIC). METHODS: The clinical data and data of blood routine indexes, blood coagulation indexes and TEG indexes of acute 155 DIC patients were collected and analyzed retrospectively. RESULTS: The CDSS scores of DIC and non-DIC groups were 9.2±1.4 and 4.2±1.1 respectively, and the CDSS scores of DIC group was significantly higher than those in non-DIC group(P<0.05). The PLT level in DIC group was significantly lower than that in non-DIC group(P<0.05), the PT, APTT, INT, DD and FIB levels in DIC group were significantly higher than those in non-DIC group(P<0.05). The R time, K time and LY30 in DIC group were significantly higher than those in non-DIC group(P<0.05), and the α and MA in DIC group were significantly lower than those in non-DIC group(P<0.05). ROC curve analysis showed that the best cutoff value of R time, K time, α, MA and LY30 were 8.4 min, 6.2 min, 52.5°, 43.2 mm and 6.7% respectively. The AUC of total scores≥1, ≥2, ≥3 and ≥4 were 0.552, 0.650, 0.687 and 0.613 respectively. CONCLUSION: The TEG possesses the certain value in the diagnosing of DIC.

17.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(5): 1718-1725, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33067980

RESUMO

OBJECTIVE: To investigate the adenovirus-mediated expression of human clotting factor IX (hFIX) gene in mouse adipose-derived stem cells(ADSC). METHODS: The mouse ADSC were isolated and cultured in vitro, the morphology of cells was observed and its growth viability was detected by using CCK-8. Cell surface markers CD29,CD90,CD45 were identified by flow cytometry, and its diferentiation ability was identified by adipogenic and osteogenic induction. Morphological changes was observed and the growth curve should be drawn after transfecting ADSC with adenovirus containing hFIX gene. The expression of hFIX gene was detected by RT-PCR. The expression of hFIX protein in ADSC or in culture supernatant was detected by Western blot. hFIX protein in the supernatant was measured by ELISA, and the clotting factor activity of hFIX in culture supernatant was measured by one-stage method. RESULTS: The in vitro cultured mouse ADSC displayed microspherical shape and strong refractive property. Anchoring growth was lasted for 4-6 hours after planting into culture flask. After cultured for 72 hours, the cells showed long spindle-shaped fibrous and swirling arrangement. The overall growth trend of the third generation ADSC cultured in vitro was S-shaped. The formation of lipid droplets could be observed in the induced cells with Oil red O staining by inverted microscope. After alizarin red staining, the orange-red calcified bone nodes were observed in the induced cells under inverted phase contrast microscope. CD29 (99.91%) and CD90 (99.02%) highly expressed in the third generation of ADSC, but CD45 (0.94%) almost not expressed. RT-PCR showed the hFIX gene could expressed in mouse ADSC. Western blot showed that hFIX protein expressed in both ADSC and culture supernatant. FIX:Ag in cell supernatant was 21.33±3.93 ng/(106 cells.24 h) on the first day, 12.63±0.86 ng/(106 cells.24 h) on the third day and 12.63±2.36 ng/(106 cells.24 h) on the ninth day. FIX:C in culture supernatant was 8.5%. CONCLUSION: Adenovirus-carried hFIX gene can effectively transfect ADSC. ADSC modified by hFIX gene can secrete hFIX protein with coagulation activity.

18.
Virulence ; 11(1): 1379-1393, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33073687

RESUMO

Entry of circovirus into the host cell nucleus is essential for viral replication during the early stage of infection. However, the mechanisms by which nucleolar shuttle proteins are used during viral replication is still not well understood. Here, we report a previously unidentified nucleolar localization signal in circovirus capsid protein (Cap), and that circovirus hijacks the nucleolar phosphoprotein nucleophosmin-1 (NPM1) to facilitate its replication. Colocalization analysis showed that NPM1 translocates from the nucleolus to the nucleoplasm and cytoplasm during viral infection. Coimmunoprecipitation and glutathione S-transferase pull-down assays showed that Cap interacts directly with NPM1. Binding domain mapping showed that the arginine-rich N-terminal motif 1MTYPRRRYRRRRHRPRSHLG20 of Cap, and residue serine-48 of the N-terminal oligomerization domain of NPM1, are essential for the interaction. Virus rescue experiments showed that all arginine to alanine substitution in the N-terminal arginine-rich motif of Cap resulted in diminished viral replication. Knockdown of NPM1 and substitution of serine-48 in NPM1 to glutamic acid also decreased viral replication. In addition, binding assays showed that the arginine-rich motif of Cap is a nucleolar localization signal. Taken together, our findings demonstrate that circovirus protein Cap is a nucleolus-located, and regulates viral replication by directly binding to NPM1.

19.
Cancer Biomark ; 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-33074217

RESUMO

Gastric cancer (GC) remains poor prognosis and survival issues due to the resistance of chemotherapies, such as cisplatin. The long non-coding RNA small nucleolar RNA host gene 7 (lncRNA-SNHG7) is known as an oncogenic molecule in diverse cancers. Here, we demonstrate that SNHG7 was significantly upregulated in gastric cancer and positively correlated with cisplatin resistance of gastric cancer cells that SNHG7 was significantly upregulated in cisplatin resistant cells. Silencing SNHG7 dramatically sensitized cisplatin resistant cells. In contrast, a negative correlation between lncRNA-SNHG7 and miR-34a was found that miR-34a was downregulated in gastric cancer patient tissues and significantly sensitized cisplatin resistant gastric cancer cells. Intriguingly, bioinformatical analysis indicated miR-34a has putative biding site for SNHG7 and such negative association between SNHG7 and miR-34a was verified in gastric cancer tissues. The cisplatin resistant cells displayed increased glycolysis rate and SNHG7 promoted cellular glycolysis rate of gastric cancer cells. Luciferase assay illustrated LDHA, a glycolysis enzyme, was the direct target of miR-34a. Importantly, inhibiting SNHG7 successfully suppressed LDHA expressions and sensitized cisplatin resistant cells and such inhibitory effects could be recovered by further anti-miR-34a. These findings suggest an important regulator mechanism for the SNHG7-mediated cisplatin resistance via miR-34a/LDHA-glycolysis axis.

20.
Neurol Res ; : 1-7, 2020 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-32985377

RESUMO

OBJECTIVE: As an intravenous anesthetic, propofol has been exhibited to provide excellent clinical analgesia. Whether propofol has amelioration property for NP and neuroinflammation remains unexplored. The present study was arranged to probe the role of propofol in the mitigation of NP and neuroinflammation in rats and underlying mechanisms. METHODS: Rats were randomly classified into the following groups: Model, Sham, Control, Propofol, GW9662, and Saline groups. The radiant heat stimulation was used to measure paw withdrawal latency (PWL), and mechanical stimulation was employed to detect paw withdrawal threshold (PWT). Subsequently, the expression of GFAP was assessed by immunofluorescence to reflect the activation of astrocyte. qRT-PCR and Western blot were utilized for the performance of mRNA and protein expression levels of PPAR γ as well as inflammation factors (TNF-α, IL-1ß, and IL-6). RESULTS: Pentobarbital sodium anesthesia significantly shortened the PWL and PWT, suppressed PPAR γ expression in rats in addition to elevating astrocyte activation and inflammation response. Propofol treatment attenuated the NP of rats as evidenced by restrained astrocyte activation level and inflammation factor levels. Rats treated with propofol had markedly heightened PPAR γ expression. PPAR γ exposure ameliorated NP and inflammation degree, which demonstrated by elevated astrocyte activation and inflammation levels as well as suppressed PWL and PWT in rats injected with PPAR γ inhibitor. Besides, PPAR γ decreased the expression level of ß-catenin. CONCLUSION: Propofol ameliorates NP and neuroinflammation of rats by up-regulating PPAR γ expression to block the Wnt/ß-catenin pathway.

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