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1.
Genes (Basel) ; 11(10)2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-33003346

RESUMO

Preeclampsia is a multi-systemic syndrome that presents in approximately 5% of pregnancies worldwide and is associated with a range of subsequent postpartum and postnatal outcomes, including fetal growth restriction. As the placenta plays a critical role in the development of preeclampsia, surveying genomic features of the placenta, including expression of imprinted genes, may reveal molecular markers that can further refine subtypes to aid targeted disease management. In this study, we conducted a comprehensive survey of placental imprinted gene expression across early and late onset preeclampsia cases and preterm and term normotensive controls. Placentas were collected at delivery from women recruited at the Magee-Womens Hospital prenatal clinics, and expression levels were profiled across 109 imprinted genes. We observed downregulation of placental Mesoderm-specific transcript (MEST) and Necdin (NDN) gene expression levels (false discovery rate (FDR) < 0.05) among early onset preeclampsia cases compared to preterm controls. No differences in placental imprinted gene expression were observed between late onset preeclampsia cases and term controls. While few studies have linked NDN to pregnancy complications, reductions in MEST expression levels, as observed in our study, are consistently reported in the literature in relation to various pregnancy complications, including fetal growth restriction, suggesting a potential role for placental MEST expression as a biosensor of an adverse in utero environment.

2.
BMC Anesthesiol ; 20(1): 254, 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-32998697

RESUMO

BACKGROUND: Perioperative neurocognitive disorders (PND) is a common postoperative complication including postoperative delirium (POD), postoperative cognitive decline (POCD) or delayed neurocognitive recovery. It is still controversial whether the use of intraoperative cerebral function monitoring can decrease the incidence of PND. The purpose of this study was to evaluate the effects of different cerebral function monitoring (electroencephalography (EEG) and regional cerebral oxygen saturation (rSO2) monitoring) on PND based on the data from randomized controlled trials (RCTs). METHODS: The electronic databases of Ovid MEDLINE, PubMed, EMBASE, Cochrane Library database were systematically searched using the indicated keywords from their inception to April 2020. The odds ratio (OR) or mean difference (MD) with 95% confidence interval (CI) were employed to analyze the data. Heterogeneity across analyzed studies was assessed with chi-square test and I2 test. RESULTS: Twenty two RCTs with 6356 patients were included in the final analysis. Data from 12 studies including 4976 patients were analyzed to assess the association between the EEG-guided anesthesia and PND. The results showed that EEG-guided anesthesia could reduce the incidence of POD in patients undergoing non-cardiac surgery (OR: 0.73; 95% CI: 0.57-0.95; P = 0.02), but had no effect on patients undergoing cardiac surgery (OR: 0.44; 95% CI: 0.05-3.54; P = 0.44). The use of intraoperative EEG monitoring reduced the incidence of POCD up to 3 months after the surgery (OR: 0.69; 95% CI: 0.49-0.96; P = 0.03), but the incidence of early POCD remained unaffected (OR: 0.61; 95% CI: 0.35-1.07; P = 0.09). The remaining 10 studies compared the effect of rSO2 monitoring to routine care in a total of 1380 participants on the incidence of PND. The results indicated that intraoperative monitoring of rSO2 could reduce the incidence of POCD (OR 0.53, 95% CI 0.39-0.73; P < 0.0001), whereas no significant difference was found regarding the incidence of POD (OR: 0.74; 95% CI: 0.48-1.14; P = 0.17). CONCLUSIONS: The findings in the present study indicated that intraoperative use of EEG or/and rSO2 monitor could decrease the risk of PND. TRIAL REGISTRATION: PROSPREO registration number: CRD42019130512 .

3.
Protein J ; 2020 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-33009960

RESUMO

Interleukin enhancer-binding factor 2 (ILF2) forms a heterodimer with interleukin enhancer-binding factor 3 (ILF3) via double-stranded RNA-binding motif and zinc finger associated domain and thus regulates gene expression and cancer cell growth. However, how ILF2 is degraded in cells remains elusive. In this work, using stable isotope labeling by amino acids in cell culture (SILAC) quantitative proteomics, we find that ILF2 is downregulated in cells expressing cereblon (CRBN). Using affinity purification and immunoblotting analysis, we demonstrate that CRBN interacts with ILF2 and functions as a substrate receptor of the cullin-4 RING E3 ligase complex. Biochemical experiments disclose that CRBN expression reduces ILF2 protein level and this reduction is diminished when the proteasome is inhibited. Upon protein synthesis inhibition, the degradation of ILF2 is enhanced by CRBN. Moreover, CRBN promotes the ubiquitination of ILF2 and thus results in the ubiquitin-mediated proteasomal degradation. Analyses of previously identified post-translational modification sites and the crystal structure of ILF2 discover the potential ubiquitination sites on ILF2. Through mutagenesis and biochemical experiments, we further reveal that the K45R mutation completely abolishes the effect of CRBN on ILF2, suggesting that this is the key residue responsible for its ubiquitination. Taken together, we identify an E3 ligase that regulates ILF2 and uncover a molecular pathway for its degradation. This work might be helpful to elucidate the molecular mechanism by which CRBN regulates diverse cellular functions.

4.
BMC Med Genet ; 21(1): 192, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33004012

RESUMO

BACKGROUND: Joubert syndrome (OMIM 213300) is an autosomal recessive disorder with gene heterogeneity. Causal genes and their variants have been identified by sequencing or other technologies for Joubert syndrome subtypes. CASE PRESENTATION: A two-year-old boy was diagnosed with Joubert syndrome by global development delay and molar tooth sign of mid-brain. Whole exome sequencing was performed to detect the causative gene variants in this individual, and the candidate pathogenic variants were verified by Sanger sequencing. We identified two pathogenic variants (NM_006346.2: c.1147delC and c.1054A > G) of PIBF1 in this Joubert syndrome individual, which is consistent with the mode of autosomal recessive inheritance. CONCLUSION: In this study, we identified two novel pathogenic variants in PIBF1 in a Joubert syndrome individual using whole exome sequencing, thereby expanding the PIBF1 pathogenic variant spectrum of Joubert syndrome.

5.
Artigo em Inglês | MEDLINE | ID: mdl-33020163

RESUMO

Background: The pharmacological activity of ceftriaxone depends on unbound concentration. However, direct measurement of unbound concentration is obstructive, and high individual variability of the unbound fraction of ceftriaxone was shown in children. We aim to evaluate and validate a method to predict unbound ceftriaxone in pediatric patients.Methods: Ninety-five pairs of concentration (total and unbound) from 92 patients were measured by the bioanalysis method we developed. The predictive performance of the three equations (empirical in vivo equation, disease adapted equation and multiple linear regression equation) was assessed by mean absolute prediction error (MAPE), mean prediction error (MAE), the proportion of the prediction error within ± 30% (P30) and ± 50% (P50) and linear regression of predicted versus actual unbound levels (R2).Results: The average total and unbound ceftriaxone concentrations were 126.18 ± 81.46 µg/mL and 18.82 ± 21.75 µg/mL, and the unbound fraction varied greatly from 4.75% to 39.97%. The MPE, MAPE, P30, P50 and R2 of empirical in vivo equation, disease equation and multiple linear equation were -.0.17 vs 0.00 vs 0.06, 0.24 vs 0.15 vs 0.27, 63.2% vs 89.5% vs 74.7% and 96.8% vs 97.9% vs 86.3% and 0.8730 vs 0.9342 vs 0.9315. The disease adapted equation showed the best predictive performance.Conclusion: We have developed and validated a bioanalysis method with one-step extraction pre-treatment for the determination of total ceftriaxone, and a prediction equation of unbound concentration was recommended. The proposed method can facilitate the clinical practice and research of unbound ceftriaxone in children.

6.
J Cell Physiol ; 2020 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-33020901

RESUMO

Long intergenic noncoding RNAs (lincRNAs) play a vital role in the occurrence and progression of cancer. The mechanism of lincRNAs in colorectal cancer (CRC) has not been fully elucidated. In this context, an integrated comparative long noncoding RNA (lncRNA) microarray technology was used to determine the expression profile of lncRNAs in CRC. The roles of LINC00908 are unclear. We found that LINC00908 was significantly upregulated in CRC. Inhibition of LINC00908 resulted in reduced cell proliferation and G1 cell cycle arrest, which was mediated by cyclin D1, cyclin-dependent kinase 4, and phosphorylated retinoblastoma. Moreover, inhibition of LINC00908-induced apoptosis through the intrinsic apoptosis signaling pathway, as shown by the activation of caspase-9 and caspase-3. Mechanistically, miR-143-3p directly bound to LINC00908. miR-143-3p expression was negatively correlated with LINC00908 expression in CRC tissue. Functional experiments revealed opposing roles for miR-143-3p and LINC00908, suggesting that LINC00908 negatively regulates miR-143-3p. Mechanistically, miR-143-3p directly targets LINC00908. The KLF5 inhibitor ML264 affected proliferation and apoptosis, indicating that LINC00908 may act as a competing endogenous RNA to facilitate the expression of the miR-143-3p target gene KLF5. Thus, LINC00908 has an important proliferative and antiapoptotic role in CRC by regulating the cell cycle and intrinsic apoptosis. LINC00908 could be a potential biomarker and a new therapeutic target for CRC.

7.
Biochem Pharmacol ; 182: 114266, 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33035506

RESUMO

Natural compounds have been confirmed as one of the most feasible solutions for hard-to-treat cancers such as hepatocellular carcinoma (HCC). Erianin, a natural bibenzyl compound from Dendrobium chrysotoxum, has been recently discovered with anticancer property in cancer cells. However, the roles and the molecular mechanisms of erianin in HCC remain unknown. The present study evaluates the effect of erianin on human HCC cells by inhibiting cell proliferation, inducing apoptotic-related cell death and hampering tumorigenicity. Furthermore, it was found that erianin could cause irreparable DNA damage, induce G2/M arrest and deregulate mitotic regulators. It was also observed that many cells with damaged DNA induced by erianin could overcome G2/M arrest and enter mitosis, leading to abnormal mitosis, and subsequently mitotic catastrophe and apoptotic-related cell death. The present study confirmed that erianin could be a potential antitumor agent for HCC clinical treatment.

8.
Cancer Commun (Lond) ; 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-33038291

RESUMO

BACKGROUND: Epigenetic regulation plays an important role in the development and progression of nasopharyngeal carcinoma (NPC). However, the epigenetic mechanisms underlying NPC metastasis remains poorly understood. We aimed to find functional genes which regulate the metastasis of NPC and identify therapeutic targets for NPC treatment. METHODS: Bisulfite pyrosequencing was used to analyze zinc finger protein 582 (ZNF582) methylation in NPC tissues and cell lines. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blotting were used to determine the expression of ZNF582. In vitro and in vivo experiments were performed to evaluate the biological function of ZNF582 in NPC. ZNF582-targeting genes were identified by chromatin immunoprecipitation sequencing (ChIP-seq) and were confirmed by ChIP-qPCR and luciferase assay. RESULTS: ZNF582 promoter was hypermethylated in NPC, and both the mRNA and protein levels of ZNF582 were down-regulated in NPC tissues and cell lines. The restoration of ZNF582 inhibited NPC migration, invasion, and metastasis, while the knockdown of ZNF582 promoted NPC migration, invasion, and metastasis in vitro and in vivo. ZNF582 directly regulated the transcription and expression of adhesion molecules Nectin-3 and NRXN3. Both Nectin-3 and NRXN3 were identified as functional targets of ZNF582, and the restoration or abrogation of these genes reversed the tumor suppressor effect of ZNF582 in NPC metastasis. CONCLUSIONS: ZNF582 acts as a tumor suppressor gene in NPC by regulating the transcription and expression of adhesion molecules Nectin-3 and NRXN3, which may provide novel therapeutic targets for NPC treatment.

9.
Mol Med Rep ; 22(5): 4396-4402, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33000234

RESUMO

Multiple acyl­CoA dehydrogenase deficiency (MADD) is a rare autosomal recessive disorder of fatty acid metabolism caused by defects in electron transfer flavoprotein (ETF) or electron transfer flavoprotein dehydrogenase (ETFDH). These defects are mainly classified into the neonatal and late­onset types, based on their clinical manifestations. ETFDH gene mutations are generally considered to be associated with the late­onset type. The present study reported an adult woman with late­onset MADD accompanied with biochemical and muscle biopsy findings indicating metabolic disorders. Gene sequencing analysis showed that the c.1514T>C homozygous mutation in the region of the 12th exon of the ETFDH gene, which led to the amino acid substitution p.I505T (isoleucine > threonine), resulting in defective ETFDH protein function. The results of family verification revealed that the homozygous mutation originated from her parents. The female patient was treated with a large dose of vitamin B2, L­carnitine and coenzyme Q10, and the symptoms were significantly relieved. The c.1514T>C mutation in the ETFDH gene, was considered as a novel pathogenic mutation that had not been previously reported. Therefore, it was hypothesized that this mutation was responsible for the clinical characteristics of the adult female patient. Overall, this novel mutation could expand the spectrum of the ETFDH gene mutation and provide the basis for the etiological and prenatal diagnosis of MADD.

10.
Respiration ; : 1-8, 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33032277

RESUMO

BACKGROUND: Most data about the trachea are collected during deep inspiration breath holding (DIBH) using multi-detector computed tomography (MDCT). Images of the physiological changes in the central airway are lacking. OBJECTIVE: The aim of this study was to explore the physiological changes in the central airway on MDCT during DIBH and deep expiration breath holding (DEBH). METHOD: The data from 62 patients (38 men and 24 women) who underwent enhanced computed tomography in our hospital were collected. Patients were grouped according to sex and age (18-45, 46-60, and >61 years). Anteroposterior diameter (APD) and transverse diameter (TD) at 3 levels (cricoid, intrathoracic inlet, and 2 cm above the carina), tracheal length, bronchial length, and subcarina angle (SCA) were measured. RESULTS: The average length of the trachea from the cricoid cartilage to the carina was 103.91 ± 10.37 mm at DEBH and 108.63 ± 11.31 mm at DIBH (p < 0.001). The APD of the trachea at the level of the cricoid, intrathoracic inlet, and 2 cm above the carina showed no differences between DEBH and DIBH. The TD of the trachea at the level of the cricoid, intrathoracic inlet, and 2 cm above the carina showed no differences between DEBH and DIBH. The average length of the right main bronchus during DEBH and DIBH was measured as 13.21 ± 3.60 and 13.24 ± 3.49 mm, respectively (p = 0.956). The average length of the left main bronchus at DEBH and DIBH was measured as 44.19 ± 5.50 and 44.27 ± 5.11 mm, respectively (p = 0.929). The average SCA was 81.74 ± 14.56 at DIBH, while it was 80.53 ± 14.38 at DEBH. The change in SCA between DIBH and DEBH showed no significant difference (p = 0.642). CONCLUSIONS: The APD at the level of the intrathoracic inlet is larger than that at the cricoid and 2 cm above the carina, while the TD is the opposite. These findings about the trachea and bronchus in our study may contribute to bronchoscopy examinations, tube applications, stent design, and stenting.

11.
J Mater Chem B ; 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33034320

RESUMO

Ultrasmall melanin nanoparticles (MNPs) have great application potential in medical imaging, owing to its satisfactory biodegradation, intrinsic photoacoustic (PA) property and natural chelating ability with metal ions for magnetic resonance imaging (MRI). Because of its ultrasmall particle size, it was easily metabolized by the kidney, but had relatively limited tumor retention according to our previous study. To further improve the intensities of MRI and PA signals for precise diagnosis, it is vital to enhance its tumor accumulation and prolong the retention time. In this study, we developed a matrix metalloproteinase-2 (MMP-2) activatable nanoprobe (PEG-PepMMP2-MNP-Gd), which was composed of water-insoluble gadolinium-chelated melanin (MNP-Gd), MMP-2 cleaved peptide and enzymatic detachable polyethylene glycol (PEG). In the presence of MMP-2 activity, PEG-coating on the surface was peeled off and the "hidden" hydrophobic segment was then exposed, which initiated the aggregation and size increase of nanoprobes. We demonstrated that the hydrodynamic size of the MMP-2 activatable nanoprobe increased from 17.1 nm to 90.2 nm after in vitro incubation with MMP-2. Moreover, the in vivo T1-weighted MRI and PA signals in tumors were both dramatically enhanced and extended after the PEG-PepMMP2-MNP-Gd nanoparticles were intravenously injected into mice. This could be attributed to the changed size selectively activated by highly expressed MMP-2 in tumors, and allowing nanoparticles to possess higher tumor accumulation and longer retention. In short, MMP2-initiated size-changeable PEG-PepMMP2-MNP-Gd could meet the paradoxical demand for size-leading permeability and retention in solid tumors, suggesting its promising applications as a highly efficient MRI/PA contrast agent for precise tumor diagnosis.

12.
ACS Nano ; 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33034444

RESUMO

Owning triply periodic minimal surfaces and three-dimensional (3D) interconnected pores, bicontinuous porous materials have drawn enormous attention due to their great academic interest and potential applications in many fields including energy and catalysis. However, their synthesis has remained a great challenge. Here, we demonstrate the synthesis of a bicontinuous porous organic semiconductor photocatalyst, which involves the preparation of SiO2 with a shifted double diamond (DD) structure through solvent evaporation-induced self-assembly of a polystyrene-block-poly(ethylene oxide) diblock copolymer and tetraethyl orthosilicate, followed by SiO2-templated self-condensation of melamine monomers in a vacuum. Strikingly, the resultant DD-structured graphitic carbon nitride (g-CN) possesses two sets of 3D continuous mesopores with a mean diameter of 14 nm, which afford a high specific surface area of 131 m2 g-1 and an optical band gap of 2.8 eV. Being a visible-light-driven photocatalyst, the bicontinuous mesoporous g-CN exhibits high catalytic activity for water splitting to generate H2 (6831 µmol g-1 h-1) with excellent cycling stability. This study provides a protocol for the construction of ordered mesoporous materials containing 3D continuous channels, which holds promise for catalysis applications.

13.
J Cardiothorac Surg ; 15(1): 291, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33008467

RESUMO

BACKGROUND: Concomitant bipolar radiofrequency ablation and valve replacement in the elderly remains controversial. In the current study, we aimed to compare the outcomes of concomitant valve replacement and bipolar radiofrequency ablation with valve replacement alone in elderly patients with atrial fibrillation (AF). METHODS: This was a retrospective study of patients aged ≥70 years who underwent valve replacement with or without bipolar radiofrequency ablation in a single-centre between January 2006 and March 2015. The early postoperative results and long-term clinical outcomes were compared after propensity score matching. RESULTS: A total of 34 pairs of patients (73.94 ± 2.64 years old; 34 in the AF with ablation group and 34 in the AF without ablation group) were enrolled in the propensity score matching analysis. There were no significant differences between the two matched groups in terms of surgical mortality (5.88% vs. 2.94%, P = 0.555) and major postoperative morbidity. Kaplan-Meier analysis revealed a significantly better overall survival in the AF with ablation group compared to the AF without ablation group (P = 0.009). Cumulative incidence curves showed a lower incidence of cardiovascular death in the AF with ablation group (P = 0.025, Gray's test). Patients in the AF with ablation group had a reduced incidence of stroke compared to patients in the AF with ablation group (P = 0.009, Gray's test). The freedom from AF after 5 years was 58.0% in the AF with ablation group and 3.0% in the AF without ablation group. CONCLUSIONS: The addition of bipolar radiofrequency ablation is a safe and feasible procedure, even in patients aged ≥70 years, with a better long-term survival and a reduced incidence of stroke compared to valve replacement alone. These findings suggest that bipolar radiofrequency ablation should always be considered as a concomitant procedure for elderly patients with AF who require cardiac surgery. However, a large-scale, prospective, multi-centre, randomized study should be performed in the future to fully validate our findings.


Assuntos
Ablação por Cateter , Doenças das Valvas Cardíacas/cirurgia , Idoso , Fibrilação Atrial/cirurgia , Procedimentos Cirúrgicos Cardíacos , Ablação por Cateter/métodos , Cateteres , Feminino , Humanos , Incidência , Masculino , Período Pós-Operatório , Pontuação de Propensão , Estudos Retrospectivos , Resultado do Tratamento
14.
Nanoscale ; 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33029601

RESUMO

A transition metal phosphide is an excellent candidate for supercapacitors due to its superior electrical conductivity and high theoretical capacity. In addition, compared with traditional 3D nano-materials, 2D nanosheets possess a greater specific surface area and shorter electron transport distance. In this study, a reasonable approach is proposed for the synthesis of ZIF-67 nanosheets on nickel foam with subsequent phosphorization by chemical vapor deposition (CVD) to obtain flake-like CoP combined with Ni2P (NCP/NF), in which nickel foam serves as the current collector as well as the resource of Ni to form Ni2P. Benefiting from the nanosheet array of CoP, the NCP/NF can improve the capacity of Ni2P from 0.57 C cm-2 to 1.43 C cm-2 at 1 mA cm-2. Furthermore, the NPC/NF/reduced graphene oxide (RGO) asymmetric supercapacitor (ASC) shows an energy density of 26.9 µW h cm-2 at a power density of 0.896 mW cm-2, and excellent cycling performance with a capacity retention of 93.75% after 5000 cycles at 10 mA cm-2.

15.
Front Immunol ; 11: 2063, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33013872

RESUMO

Background: Cases of excessive neutrophil counts in the blood in severe coronavirus disease (COVID-19) patients have drawn significant attention. Neutrophil infiltration was also noted on the pathological findings from autopsies. It is urgent to clarify the pathogenesis of neutrophils leading to severe pneumonia in COVID-19. Methods: A retrospective analysis was performed on 55 COVID-19 patients classified as mild (n = 22), moderate (n = 25), and severe (n = 8) according to the Guidelines released by the National Health Commission of China. Trends relating leukocyte counts and lungs examined by chest CT scan were quantified by Bayesian inference. Transcriptional signatures of host immune cells of four COVID19 patients were analyzed by RNA sequencing of lung specimens and BALF. Results: Neutrophilia occurred in 6 of 8 severe patients at 7-19 days after symptom onset, coinciding with lesion progression. Increasing neutrophil counts paralleled lesion CT values (slope: 0.8 and 0.3-1.2), reflecting neutrophilia-induced lung injury in severe patients. Transcriptome analysis revealed that neutrophil activation was correlated with 17 neutrophil extracellular trap (NET)-associated genes in COVID-19 patients, which was related to innate immunity and interacted with T/NK/B cells, as supported by a protein-protein interaction network analysis. Conclusion: Excessive neutrophils and associated NETs could explain the pathogenesis of lung injury in COVID-19 pneumonia.


Assuntos
Betacoronavirus/genética , Infecções por Coronavirus/imunologia , Armadilhas Extracelulares/genética , Ativação de Neutrófilo/genética , Neutrófilos/imunologia , Pneumonia Viral/imunologia , Adulto , Idoso , Teorema de Bayes , Infecções por Coronavirus/virologia , Feminino , Humanos , Contagem de Leucócitos , Lesão Pulmonar/imunologia , Lesão Pulmonar/patologia , Masculino , Pessoa de Meia-Idade , Infiltração de Neutrófilos/imunologia , Pandemias , Pneumonia Viral/virologia , Mapas de Interação de Proteínas/imunologia , RNA Viral/genética , Estudos Retrospectivos , Transcriptoma
17.
J Food Sci ; 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33078395

RESUMO

Grape skins produced during the grape juice production and processing contain abundant anthocyanins and other active compounds. Consequently, this study optimized the extraction conditions for ultrasound-assisted enzymatic extraction (UAEE) of anthocyanins from grape skins via response surface methodology coupled with genetic algorithm. The optimum extraction parameters to achieve the highest anthocyanins yield (3.01 ± 0.04) mg/g from grape skins by UAEE were obtained under an extraction temperature of 50 °C, ultrasonic power of 400 W, pectinase dosage of 0.16%, and extraction time of 28 min. The AB-8 macroporous resin combined Sephadex LH-20 techniques were further employed to purify the anthocyanins extracts obtained under optimum extraction conditions (AEOEC), and the main anthocyanins were identified using high-performance liquid chromatography tandem mass spectrometry. The purified anthocyanins contained two anthocyanins in terms of delphinidin-3,5-O-diglucoside and cyanidin-3-O-rutinoside with purity of 91.35% and 92.64%, respectively. Ultimately, we further evaluated the antitumor activity of AEOEC and two purified anthocyanins on breast cancer. The results indicated that the antitumor effect of AEOEC on breast cancer MCF-7 cells was better than that of two purified anthocyanins. In addition, AEOEC could memorably increase intracellular reactive oxygen species levels and apoptosis of MCF-7 cells, and arrest MCF-7 cells in the G2/M phases. The findings provide an effective and feasible method for anthocyanins extraction and reduce the environmental burden of this waste.

18.
Neurosci Bull ; 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33067780

RESUMO

Trigeminal neuralgia is a debilitating condition, and the pain easily spreads to other parts of the face. Here, we established a mouse model of partial transection of the infraorbital nerve (pT-ION) and found that the Connexin 36 (Cx36) inhibitor mefloquine caused greater alleviation of pT-ION-induced cold allodynia compared to the reduction of mechanical allodynia. Mefloquine reversed the pT-ION-induced upregulation of Cx36, glutamate receptor ionotropic kainate 2 (GluK2), transient receptor potential ankyrin 1 (TRPA1), and phosphorylated extracellular signal regulated kinase (p-ERK) in the trigeminal ganglion. Cold allodynia but not mechanical allodynia induced by pT-ION or by virus-mediated overexpression of Cx36 in the trigeminal ganglion was reversed by the GluK2 antagonist NS102, and knocking down Cx36 expression in Nav1.8-expressing nociceptors by injecting virus into the orofacial skin area of Nav1.8-Cre mice attenuated cold allodynia but not mechanical allodynia. In conclusion, we show that Cx36 contributes greatly to the development of orofacial pain hypersensitivity through GluK2, TRPA1, and p-ERK signaling.

19.
Nat Commun ; 11(1): 5035, 2020 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-33028823

RESUMO

Aliphatic α,ω-dicarboxylic acids (DCAs) are a class of useful chemicals that are currently produced by energy-intensive, multistage chemical oxidations that are hazardous to the environment. Therefore, the development of environmentally friendly, safe, neutral routes to DCAs is important. We report an in vivo artificially designed biocatalytic cascade process for biotransformation of cycloalkanes to DCAs. To reduce protein expression burden and redox constraints caused by multi-enzyme expression in a single microbe, the biocatalytic pathway is divided into three basic Escherichia coli cell modules. The modules possess either redox-neutral or redox-regeneration systems and are combined to form E. coli consortia for use in biotransformations. The designed consortia of E. coli containing the modules efficiently convert cycloalkanes or cycloalkanols to DCAs without addition of exogenous coenzymes. Thus, this developed biocatalytic process provides a promising alternative to the current industrial process for manufacturing DCAs.

20.
Arch Virol ; 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33067648

RESUMO

Avian infectious bronchitis (IB) is a highly contagious viral respiratory disease, caused by infectious bronchitis virus (IBV), that poses an important economic threat to the poultry industry. In recent years, genotypes GI-7, GI-13, and GI-19 have been the most prevalent IBV strains in China. However, in this study, we found that most IBV strains from southern China in 2016-2017 belonged to genotype GVI-1. This genotype, for which there is no vaccine, has been reported sporadically in the region. The GDTS13 strain, which caused severe IB outbreaks on the farms where it was isolated, was evaluated as a candidate vaccine strain. GDTS13 was serially passaged in specific-pathogen-free embryonated chicken eggs for 100 generations to produce GDTS13-F100. Safety testing indicated that GDTS13-F100 had no pathogenic effect on chickens. Additionally, GDTS13-F100 showed an excellent protective effect against GDTS13, with no clinical signs or virus shedding observed in immunized chickens challenged with the parent strain. These findings indicate that GVI-1 has become the most prevalent IBV genotype in southern China and that GDTS13-F100 may serve as an attenuated vaccine to protect against infection with this genotype.

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