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1.
Cell Death Discov ; 7(1): 246, 2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34535633

RESUMO

Transcriptional factor nuclear factor κB (NF-κB) can be activated by various intracellular or extracellular stimuli and its dysregulation leads to pathological conditions, such as neurodegenerative disorders, infection, and cancer. The carboxyl terminus of HSC70-interacting protein (CHIP), a pathogenic gene of spinocerebellar autosomal recessive 16 (SCAR16), plays an important roles in protein degradation, trafficking, and multiple signaling transductions. It has been reported that CHIP participates in the regulation of NF-κB signaling, and the mutant of CHIP (p.T246M) leads to the occurrence of SCAR16. However, the detailed mechanism of CHIP and CHIP (p.T246M) in the regulation of NF-κB signaling in neurological disorders remains unclear. Here, we found that CHIP promoted the activation of NF-κB signaling, while the knockdown had the opposite effect. Furthermore, CHIP interacted with TAK1 and targeted it for K63-linked ubiquitination. Finally, CHIP enhanced the interaction between TAK1 and NEMO. However, CHIP (p.T246M) couldn't upregulate NF-κB signaling, potentiate the ubiquitination of TAK1, and enhance the interactions. Taken together, our study demonstrated for the first time that CHIP positively regulates NF-κB signaling by targeting TAK1 and enhancing its K63-linked ubiquitination.

2.
Adv Mater ; 33(41): e2103392, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34436805

RESUMO

Corner-sharing oxides usually suffer from structural reconstruction during the bottleneck oxygen-evolution reaction (OER) in water electrolysis. Therefore, introducing dynamically stable active sites in an alternative structure is urgent but challenging. Here, 1D 5H-polytype Ba5 Bi0.25 Co3.75 FeO14- δ oxide with face-sharing motifs is identified as a highly active and stable candidate for alkaline OER. Benefiting from the stable face-sharing motifs with three couples of combined bonds, Ba5 Bi0.25 Co3.75 FeO14- δ can maintain its local structures even under high OER potentials as evidenced by fast operando spectroscopy, contributing to a negligible performance degradation over 110 h. Besides, the higher Co valence and smaller orbital bandgap in Ba5 Bi0.25 Co3.75 FeO14- δ endow it with a much better electron transport ability than its corner-sharing counterpart, leading to a distinctly reduced overpotential of 308 mV at 10 mA cm-2 in 0.1 m KOH. Further mechanism studies show that the short distance between lattice-oxygen sites in face-sharing Ba5 Bi0.25 Co3.75 FeO14- δ can accelerate the deprotonation step (*OOH + OH-  = *OO + H2 O + e- ) via a steric inductive effect to promote lattice-oxygen participation. In this work, not only is a new 1D face-sharing oxide with impressive OER performance discovered, but also a rational design of dynamic stable and active sites for sustainable energy systems is inaugurated.

3.
Polymers (Basel) ; 13(16)2021 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-34451322

RESUMO

The emergence of antibiotic-resistant "superbugs" in recent decades has led to widespread illness and death and is a major ongoing public health issue. Since traditional antimicrobials and antibiotics are in many cases showing limited or no effectiveness in fighting some emerging pathogens, there is an urgent need to develop and explore novel antibacterial agents that are both powerful and reliable. Combining two or more antibiotics or antimicrobials has become a hot topic in antibacterial research. In this contribution, we report on using a simple electrospinning technique to create an N-halamine/graphene oxide-modified polymer membrane with excellent antibacterial activity. With the assistance of advanced techniques, the as-obtained membrane was characterized in terms of its chemical composition, morphology, size, and the presence of active chlorine. Its antibacterial properties were tested with Escherichia coli (E. coli) as the model bacteria, using the colony-counting method. Interestingly, the final N-halamine/graphene oxide-based antibacterial fibrous membrane inactivated E. coli both on contact and by releasing active chlorine. We believe that the synergistic antimicrobial action of our as-fabricated fibrous membrane should have great potential for utilization in water disinfection, air purification, medical and healthcare products, textile products, and other antibacterial-associated fields.

4.
Chem Asian J ; 2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34384002

RESUMO

Graphene oxide (GO) is a promising two-dimensional building block for fabricating high-performance gas separation membranes. Whereas the tortuous transport pathway may increase the transport distance and lead to a low gas permeation rate, introducing spacers into GO laminates is an effective strategy to enlarge the interlayer channel for enhanced gas permeance. Herein, we propose to intercalate CO2 -philic MIL-101(Cr) metal-organic framework nanocrystals into the GO laminates to construct a 2D/3D hybrid structure for gas separation. The interlayer channels were partially opened up to accelerate gas permeation. Meanwhile, the intrinsic pores of MIL-101 provided additional transport pathways, and the affinity of MIL-101 to CO2 molecules resulted in higher H2 /CO2 diffusion selectivity, leading to a simultaneous enhancement in gas permeance and separation selectivity. The MIL-101(Cr)/GO membrane with optimal structures exhibited outstanding and stable mixed-gas separation performance with H2 permeance of 67.5 GPU and H2 /CO2 selectivity of 30.3 during the 120-h continuous test, demonstrating its potential in H2 purification application.

5.
Medicine (Baltimore) ; 100(33): e26964, 2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34414965

RESUMO

ABSTRACT: Hepatocellular carcinoma (HCC) is one of the tumors with a higher mortality rate globally, which significantly threatens people's health. Hepatitis C virus (HCV) infection is a major driving factor of HCC. This study aims to determine the key microRNA (miRNA), hub genes, and related pathways, construct potential miRNA-mRNA regulatory networks, and clarify the new molecular mechanism of HCV-related HCC. In this study, 16 differentially expressed miRNAs (DE miRNAs) were identified. The prediction of potential transcription factors and target genes not only found that SP1 and ERG1 may potentially regulate most of the screened DE miRNAs, but it also obtained 2923 and 1782 predicted target genes for the up-regulation and down-regulation of DE miRNAs, respectively. Subsequently, the introduction of differentially expressed genes dataset GSE62232 for target gene verification yielded 98 and 147 potential up-regulation and down-regulation target genes. The gene ontology (GO) and Kyoto encyclopedia of genes and genomes pathway enrichment analysis showed that they were mainly enriched in the cell cycle process, that is, subsequently, 20 hub genes were screened out through the protein-protein interaction network, and related genes were further evaluated using the GEPIA database. Based on the above analysis, the miRNA-hub gene regulatory network was constructed. In short, this research's hub genes and miRNAs closely related to HCV-related HCC were screened and identified through bioinformatics analysis and then built their connection. These results are expected to find potential therapeutic targets for HCV-related HCC.


Assuntos
Carcinoma Hepatocelular/etiologia , Hepatite C/complicações , Neoplasias Hepáticas/etiologia , MicroRNAs/metabolismo , RNA Mensageiro/metabolismo , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/virologia , Biologia Computacional , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Regulação Viral da Expressão Gênica , Hepatite C/metabolismo , Humanos , Neoplasias Hepáticas/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos
6.
Gene ; 791: 145715, 2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-33984444

RESUMO

Leptodermis scabrida complex is one of the important components of genus Leptodermis, which is mainly distributed in the Himalaya Mountains. It includes species of L. gracilis, L. hirsutiflora, L. hirsutiflora var. ciliata, L. kumaonensis, L. pilosa var. acanthoclada and L. scabrida. However, species boundaries and relationships within this complex are unclear based on current morphological and molecular evidence. We sequenced 13 complete chloroplast (cp) genomes representing seven taxa of the complex and two non-Leptodermis scabrida complex taxa. After de novo assembly and annotation, we performed comparative genomic analysis. All cp genomes showed highly conserved structures, and the genome sizes ranged from 154,369 bp to 154,885 bp and possessed the same GC content (37.5%). A total of 113 unique genes were identified in each cp sample, including 79 protein coding genes, 30 tRNAs, and four rRNAs. Repeat sequences and SSRs were detected, showing great similarity among all taxa in this complex. Six highly variable regions, including trnS-trnG, rps2-rpoC2, ndhF, rpl32-ccsA, ccsA-ndhD, and ndhA, were screened as potential molecular markers for phylogenetic reconstruction. Based on a total of 27 complete cp genome sequences, the consistent and robust phylogenetic relationships were firstly constructed and the same species within L. scabrida complex clustered into a group. The divergence time of Leptodermis from ancestral taxa occurred at the middle Eocene, which might be due to geological and climatic changes. The 13 complete cp genome sequences reported will provide new clues for phylogeny elucidation, species identification and evolutionary history speculation of Leptodermis, as well as in Rubiaceae.


Assuntos
Genoma de Cloroplastos/genética , Rubiaceae/genética , Composição de Bases/genética , Cloroplastos/genética , Cloroplastos/metabolismo , Evolução Molecular , Tamanho do Genoma/genética , Genômica/métodos , Repetições de Microssatélites/genética , Filogenia , RNA Ribossômico/genética , Rubiaceae/metabolismo , Sequenciamento Completo do Genoma
7.
PLoS One ; 16(4): e0248380, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33891611

RESUMO

Inactivating mutations in either TSC1 or TSC2 cause Tuberous Sclerosis Complex, an autosomal dominant disorder, characterized by multi-system tumor and hamartoma development. Mutation and loss of function of TSC1 and/or TSC2 also occur in a variety of sporadic cancers, and rapamycin and related drugs show highly variable treatment benefit in patients with such cancers. The TSC1 and TSC2 proteins function in a complex that inhibits mTORC1, a key regulator of cell growth, which acts to enhance anabolic biosynthetic pathways. In this study, we identified and validated five cancer cell lines with TSC1 or TSC2 mutations and performed a kinase inhibitor drug screen with 197 compounds. The five cell lines were sensitive to several mTOR inhibitors, and cell cycle kinase and HSP90 kinase inhibitors. The IC50 for Torin1 and INK128, both mTOR kinase inhibitors, was significantly increased in three TSC2 null cell lines in which TSC2 expression was restored. Rapamycin was significantly more effective than either INK128 or ganetespib (an HSP90 inhibitor) in reducing the growth of TSC2 null SNU-398 cells in a xenograft model. Combination ganetespib-rapamycin showed no significant enhancement of growth suppression over rapamycin. Hence, although HSP90 inhibitors show strong inhibition of TSC1/TSC2 null cell line growth in vitro, ganetespib showed little benefit at standard dosage in vivo. In contrast, rapamycin which showed very modest growth inhibition in vitro was the best agent for in vivo treatment, but did not cause tumor regression, only growth delay.


Assuntos
Proteínas de Choque Térmico HSP90/antagonistas & inibidores , Neoplasias/tratamento farmacológico , Serina-Treonina Quinases TOR/antagonistas & inibidores , Animais , Benzoxazóis/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Proteínas de Choque Térmico HSP90/metabolismo , Humanos , Masculino , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Nus , Mutação/efeitos dos fármacos , Naftiridinas/farmacologia , Neoplasias/genética , Neoplasias/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Pirimidinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Esclerose Tuberosa/genética , Esclerose Tuberosa/metabolismo , Esclerose Tuberosa/patologia , Proteína 1 do Complexo Esclerose Tuberosa/genética , Proteína 1 do Complexo Esclerose Tuberosa/metabolismo , Proteína 2 do Complexo Esclerose Tuberosa/genética , Proteína 2 do Complexo Esclerose Tuberosa/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
8.
Front Cell Infect Microbiol ; 11: 631921, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33718280

RESUMO

Salmonella spp. is among the main foodborne pathogens which cause serious foodborne diseases. An isothermal real-time recombinase polymerase amplification (RPA) and lateral flow strip detection (LFS RPA) were used to detect Salmonella spp. targeting the conserved sequence of invasion protein A (invA). The Real-time RPA was performed in a portable florescence scanner at 39°C for 20 min. The LFS RPA was performed in an incubator block at 39°C for 15 min, under the same condition that the amplifications could be inspected by the naked eyes on the LFS within 5 min. The detection limit of Salmonella spp. DNA using real-time RPA was 1.1 × 101 fg, which was the same with real-time PCR but 10 times higher than that of LFS RPA assay. Moreover, the practicality of discovering Salmonella spp. was validated with artificially contaminated lamb, chicken, and broccoli samples. The analyzing time dropped from 60 min to proximately 5-12 min on the basis of the real-time and LFS RPA assays compared with the real-time PCR assay. Real-time and LFS RPA assays' results were equally reliable. There was no cross-reactivity with other pathogens in both assays. In addition, the assays had good stability. All of these helped to show that the developed RPA assays were simple, rapid, sensitive, credible, and could be a potential point-of-need (PON) test required mere resources.


Assuntos
Técnicas de Amplificação de Ácido Nucleico , Recombinases , Animais , Nucleotidiltransferases , Salmonella , Sensibilidade e Especificidade , Ovinos
9.
Plant Sci ; 306: 110862, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33775367

RESUMO

For rapid growth, moso bamboo (Phyllostachys edulis) requires large amounts of nutrients. Nitrate is an indispensable molecular signal to regulate nitrogen absorption and assimilation, which are regulated by group III NIN-LIKE PROTEINs (NLPs). However, no Phyllostachys edulis NLP (PeNLP) has been characterized. Here, eight PeNLPs were identified, which showed dynamic expression patterns in bamboo tissues. Nitrate did not affect PeNLP mRNA levels, and PeNLP1, -2, -5, -6, -7, and -8 successfully restored nitrate signaling in Arabidopsis atnlp7-1 protoplasts through recovering AtNiR and AtNRT2.1 expression. Four group I and II PeNLPs (PeNLP1, -2, -5, and -8) interacted with the nitrate-responsive cis-element of PeNiR. Moreover, nitrate triggered the nuclear retention of PeNLP8. PeNLP8 overexpression in Arabidopsis significantly increased the primary root length, lateral root number, leaf area, and dry and wet weight of the transgenic plants, and PeNLP8 expression rescued the root architectural defect phenotype of atnlp7-1 mutants. Interestingly, PeNLP8 overexpression dramatically reduced nitrate content but elevated total amino acid content in Arabidopsis. Overall, the present study unveiled the potential involvement of group I and II NLPs in nitrate signaling regulation and provided genetic resources for engineering plants with high nitrogen use efficiency.


Assuntos
Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Nitratos/metabolismo , Proteínas de Plantas/metabolismo , Poaceae/genética , Poaceae/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Genes de Plantas , Genoma de Planta , Mutação , Filogenia , Folhas de Planta/genética , Folhas de Planta/metabolismo , Proteínas de Plantas/genética , Raízes de Plantas/genética , Raízes de Plantas/metabolismo , Caules de Planta/genética , Caules de Planta/metabolismo , Plantas Geneticamente Modificadas/genética
10.
J Phys Chem Lett ; : 3046-3052, 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33739121

RESUMO

The negative photoconductivity (NPC) effect originating from the surface shell layer has been considered as an efficient approach to improve the performance of optoelectronic nanodevices. However, a scientific design and precise growth of NPC-effect-caused shell during nanowire (NW) growth process for achieving high-performance photodetectors are still lacking. In this work, GeS NWs with a controlled sulfur-rich shell, diameter, and length are successfully prepared by a simple chemical vapor deposition method. As checked by transmission electron microscopy, the thickness of the sulfur-rich shell ranges from 10.5 ± 1.5 to 13.4 ± 2.5 nm by controlling the NW growth time. The composition of the sulfur-rich shell is studied by X-ray photoelectron spectroscopy, showing the decrease of S in the GeSx shell from the surface to core. When configured into the well-known phototransistor, a featured NPC effect is observed, benefiting the high-performance photodetector with high responsivity of 105 A·W-1 and detectivity of 1012 Jones for λ = 405 nm with ultralow intensity of 0.04 mW·cm-2. However, the thicker-shell NW phototransistor shows an unstable photodetector behavior with smaller negative photocurrent because of more hole-trapping states in the thicker shell. All results suggest a careful design and controlled growth of an NPC-effect-caused shell for future optoelectronic applications.

11.
Acta Otolaryngol ; 141(4): 386-391, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33411597

RESUMO

BACKGROUND: The prevalence of eosinophilic CRSwNP in China has increased significantly over the last 20 years, noninvasive methods that could assist in diagnosis are urgently needed. AIMS: The aim of this study is to explore the clinical significance of peripheral blood eosinophil in diagnosing ECRS. MATERIALS AND METHODS: We conducted a prospective study of 221 patients diagnosed with CRS. Lund-Mackay score, peripheral blood eosinophil absolute count, peripheral blood eosinophil percentage were detection to compare the clinical features with ECRS and non-ECRS. ROC curve was performed to assess the efficiency of clinical index to predict ECRS. RESULTS: The ECRS group of patients had significantly higher scores compared with those of the non-ECRS group. Different extent and severity of mucosal thickening on total Lund-Mackay scores, anterior ethmoidal, posterior ethmoidal and ostiomeatal complex have confirmed different blood eosinophil levels in CRS patients. The combination of peripheral blood eosinophil percentage and posterior ethmoidal score to predict ECRS was 0.807. CONCLUSIONS AND SIGNIFICANCE: The increase in peripheral blood eosinophil percent indicates the deterioration the inflammation of chronic rhinosinusitis and the level of posterior ethmoidal score and peripheral blood eosinophil percentage have a positive predictive value regarding ECRS identification.

12.
Plant Dis ; 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33406862

RESUMO

In August 2017, soybean root rot plants exhibiting root rot were observed in Baiquan County (47°60'N, 126°10'E), Heilongjiang province, China. The disease occurred on approximately 65% of soybean (cv. Heihe43) plantsroots in five fields (>10 ha). The disease resulted in yellowing or wilting and smaller sized leaves, absence of lateral roots and black lesions on tap roots. Infected root tissues from 10 individual plants (2 plants/each field) were surface disinfested with 0.5% NaOCl for 2 min, rinsed three times in sterile distilled water, placed on potato dextrose agar PDA, and incubated at 26℃ for 3 days. Eight fungal isolates were obtained by transferring hyphal tips.isolated and subcultured by transferring hyphal tips. Colonies on PDA were initially white to rose, then yellow in color with abundant aerial mycelium. The fungal colonies grew to a size of 7.4 cm in diameter four days after inoculation. Macroconidia were scarce and scattered, measuring 19.7 µm× 3.5 µm (n = 50) on carnation leaf agar. Typical macroconidium had 3-5 septa, slightly sharp apices with a distinct basal foot cell. Microconidia had 0-2 septa, and were slightly curved, measuring 10.7 µm × 3.2 µm (n = 50). Spherical chlamydospores had a mean diameter of 13.7µm (n = 50), were terminal and intercalary on PDA. According to these morphological characteristics, the fungus was identified as F. brachygibbosum (Padwick1945). Genomic DNA of a representative isolate P13-1was extracted. The Ef-1α, RPB1 and RPB2 regions were amplified using primers ef1/ef2, Fa/G2R and 5f2/7cr (O'Donnell et al. 2010).The consensus sequences (accession nos. MH748277, MH748278 and MH748279) showed 98.65%, 98.91% and 99.54% identity to the sequences of F. brachygibbosum strain NRRL 34033(accession no.GQ505418.1, HM347172.1 and GQ505482.1). Isolate P13-1was preserved in Agricultural Culture Collection of China, Stock ID number is ACCC 39715.To confirm pathogenicity of P13-1, soybean (cv. Heihe43) seeds were grown in 15-cm pots containing a commercial potting mix (5seeds per pot,3 pots/ treatment). Sorghum seeds (10 g) fully colonized by F. brachygibbosum (Li et al., 2018)were uniformly distributed in each pot and then covered with a 0.5-cm layer of sterile potting soil. , Sterilized sterilized sorghum seeds(10 g) were added to control pots. , incubated in a growth chamber at 25°C (12h day) / 20°C (12h night). 10 Ten days after inoculation , all inoculated plants showed symptoms consistent with those observed in the fields. The experiment was repeated two times. F. brachygibbosum was reisolated from diseased plants and identified as F. brachygibbosum based on morphological and gene sequences analysismolecular characteristics. No fungal pathogens were isolated from nontreated controls. To our knowledge, this is the first report of F. brachygibbosum on soybean in China. The soybean is the prime oil seed crop and the source of protein cultivated in Northeast China and this disease seriously affects the seedling growth. So, our findings are very important for the establishment of control strategies and breeding for resistance to soybean root rot.

13.
Nanotechnology ; 32(14): 145203, 2021 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-33443238

RESUMO

Weak n-type characteristics or poor p-type characteristics are limiting the applications of binary semiconductors based on ambipolar field-effect transistors (FETs). In this work, a ternary alloy of In0.2Ga0.8As nanowires (NWs) is successfully prepared using a Ni catalyst during a typical solid-source chemical-vapor-deposition process to balance the weak n-type conduction behavior in ambipolar GaAs NWFETs and the poor p-type conduction behavior in ambipolar InAs NWFETs. The presence of ambipolar transport, contributed by a native oxide shell and the body defects of the prepared In0.2Ga0.8As NWs, is confirmed by the constructed back-gated NWFETs. As demonstrated by photoluminescence, the bandgap of the prepared In0.2Ga0.8As NWs is 1.28 eV, offering the promise of application in near-infrared (NIR) photodetection. Under 850 nm laser illumination, the fabricated ambipolar NWFETs show extremely low dark currents of 50 pA and 0.5 pA when positive and negative gate voltages are applied, respectively. All the results demonstrate that with careful design of the surface oxide layer and the body defects, NWs are suitable for use in next-generation optoelectronic devices.

14.
J Cell Physiol ; 236(4): 2333-2351, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32875580

RESUMO

Proprotein convertase subtilisin/kexin type-9 (PCSK9), a member of the proprotein convertase family, is an important drug target because of its crucial role in lipid metabolism. Emerging evidence suggests a direct role of localized PCSK9 in the pathogenesis of vascular diseases. With this in our consideration, we reviewed PCSK9 physiology with respect to recent development and major studies (clinical and experimental) on PCSK9 functionality in vascular disease. PCSK9 upregulates low-density lipoprotein (LDL)-cholesterol levels by binding to the LDL-receptor (LDLR) and facilitating its lysosomal degradation. PCSK9 gain-of-function mutations have been confirmed as a novel genetic mechanism for familial hypercholesterolemia. Elevated serum PCSK9 levels in patients with vascular diseases may contribute to coronary artery disease, atherosclerosis, cerebrovascular diseases, vasculitis, aortic diseases, and arterial aging pathogenesis. Experimental models of atherosclerosis, arterial aneurysm, and coronary or carotid artery ligation also support PCSK9 contribution to inflammatory response and disease progression, through LDLR-dependent or -independent mechanisms. More recently, several clinical trials have confirmed that anti-PCSK9 monoclonal antibodies can reduce systemic LDL levels, total nonfatal cardiovascular events, and all-cause mortality. Interaction of PCSK9 with other receptor proteins (LDLR-related proteins, cluster of differentiation family members, epithelial Na+ channels, and sortilin) may underlie its roles in vascular disease. Improved understanding of PCSK9 roles and molecular mechanisms in various vascular diseases will facilitate advances in lipid-lowering therapy and disease prevention.

15.
Neurosci Lett ; 741: 135457, 2021 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-33171211

RESUMO

Parkinson's disease (PD) is a neurodegenerative disease characterized by the loss of dopaminergic neurons in the substantia nigra (SN). Many factors can explain the mechanism. However, the precise mechanism that contributes to the decreased number of dopaminergic neurons is unknown. Our study shows that oxidative stress is increased in models of PD compared with WT mice; Thioredoxin reductase 1(TR1) has emerged as an important antioxidant agent in dopaminergic neurons. In summary, our findings demonstrate that the overexpression of TR1 could be developed into a novel neuroprotective strategy for PD and that the reduction of the expression of GSK-3ß and NF-κB could also be promising therapeutic strategies for PD. This research suggests a new direction in the treatment of PD.


Assuntos
Fármacos Neuroprotetores/administração & dosagem , Estresse Oxidativo , Doença de Parkinson/metabolismo , Tiorredoxina Redutase 1/administração & dosagem , Tiorredoxina Redutase 1/metabolismo , Animais , Apoptose , Linhagem Celular , Mesencéfalo/metabolismo , Camundongos , Neurônios/metabolismo , Tirosina 3-Mono-Oxigenase/metabolismo
16.
Exp Brain Res ; 239(2): 475-490, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33230666

RESUMO

Parkinson's disease (PD) is a neurodegenerative disease characterized by the loss of dopaminergic neurons in the substantia nigra (SN). Several factors, including neuroinflammation, neuronal excitotoxicity, genetic mutations and incorrect protein folding are involved in PD pathophysiology. However, the precise mechanism that contributes to the decreased number of dopaminergic neurons is unknown. A growing body of research suggests that oxidative stress is a major factor in PD. Therefore, antioxidant therapy is an important approach for treating PD. The thioredoxin system is an important antioxidant system, and thioredoxin reductase 1 (TR1) is a major member of the thioredoxin system. The present study demonstrates that oxidative stress is increased and that the expression of TR1 is decreased in the SNc of A53T mice; TR1 has emerged as an important antioxidant agent in dopaminergic neurons. Therefore, we over-expressed TR1 in the MPP+-induced cellular model and in the A53T transgenic mouse model of PD. We confirmed that the overexpression of TR1 in neuronal cells decreased DNA damage and malondialdehyde (MDA) and ROS generation, increased T-SOD and GSH production, and decreased the ER stress, and autophagy in the PD model. In summary, our findings demonstrate that the overexpression of TR1 could be effective as a novel neuroprotective strategy for PD. This research suggests a novel direction in the treatment of PD.

17.
Curr Med Chem ; 28(17): 3385-3405, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33191882

RESUMO

Monocyte chemoattractant protein-1 induced protein 1 (MCPIP1), one of the MCPIP family members, is characterized by the presence of both C-x8-C-x5-C-x3-H (CCCH)- type zinc finger and PilT-N-terminal domains. As a potent regulator of innate immunity, MCPIP1 exerts anti-inflammatory effects through its ribonuclease (RNase) and deubiquitinating enzyme activities to degrade cytokine mRNAs and inhibit nuclear factor- kappa B (NF-κB), respectively. MCPIP1 is expressed not only in immune cells but also in many other cell types, including cardiomyocytes, vascular endothelial cells (ECs) and smooth muscle cells (SMCs). Increasing evidence indicates that MCPIP1 plays a role in the regulation of cardiac functions and is involved in the processes of vascular diseases, such as ischemia-reperfusion (I/R) and atherosclerosis. To better understand the emerging roles of MCPIP1 in the cardiovascular system, we reviewed the current literature with respect to MCPIP1 functions and discussed its association with the pathogenesis of cardiovascular diseases and the implication as a therapeutic target.


Assuntos
Doenças Cardiovasculares , Ribonucleases , Fatores de Transcrição , Quimiocina CCL2 , Células Endoteliais , Humanos
18.
Arch Biochem Biophys ; 704: 108717, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-33307067

RESUMO

PCSK9 plays a critical role in cholesterol metabolism via the PCSK9-LDLR axis. Liver-derived, circulating PCSK9 has become a novel drug target in lipid-lowering therapy. Accumulative evidence supports the possible association between PCSK9 and cardiac diseases and their risk factors. PCSK9 exerts various effects in the heart independently of LDL-cholesterol regulation. Acute myocardial infarction (AMI) induces local and systemic inflammation and reactive oxygen species generation, resulting in increased PCSK9 expression in hepatocytes and cardiomyocytes. PCSK9 upregulation promotes excessive autophagy and apoptosis in cardiomyocytes, thereby contributing to cardiac insufficiency. PCSK9 might also participate in the pathophysiology of heart failure by regulating fatty acid metabolism and cardiomyocyte contractility. It also promotes platelet activation and coagulation in patients with atrial fibrillation. PCSK9 is an independent predictor of aortic valve calcification and accelerates calcific aortic valve disease by regulating lipoprotein(a) catabolism. Accordingly, the use of PCSK9 inhibitors significantly reduced infarct sizes and arrhythmia and improves cardiac contractile function in a rat model of AMI. Circulating PCSK9 levels are positively correlated with age, diabetes mellitus, obesity, and hypertension. Here, we reviewed recent clinical and experimental studies exploring the association between PCSK9, cardiac diseases, and their related risk factors and aiming to identify possible underlying mechanisms.

19.
Nanotechnology ; 2020 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-33316788

RESUMO

Weak n-type characteristics or poor p-type characteristics are limiting the applications of binary semiconductors based on ambipolar field-effect-transistors (FETs). In this work, ternary alloy of In0.2Ga0.8As nanowires (NWs) are successfully prepared by using the catalyst of Ni firstly during typical solid source chemical vapor deposition process for balancing the weak n-type conduction behavior in ambipolar GaAs NWFETs and poor p-type conduction behavior in ambipolar InAs NWFETs. The ambipolar transport is confirmed by the constructed back-gated NWFETs, contributing from the native oxide shell and body defects of as-prepared In0.2Ga0.8As NWs. As demonstrated by photoluminescence, the bandgap of as-prepared In0.2Ga0.8As NWs is 1.28 eV, promising the application of near-infrared (NIR) photodetection. Under an 850 nm laser illumination, the as-fabricated ambiploar NWFETs show extremely low dark currents of 50 pA and 0.5 pA by applying positive and negative gate voltages respectively. All of the results demonstrate the careful design of surface oxide layer and body defects of NWs for next-generation optoelectronic devices.

20.
BMC Vet Res ; 16(1): 454, 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33228636

RESUMO

BACKGROUND: Mycoplasma bovis (M. bovis) is a highly contagious cattle pathogen spreading worldwide and especially in Ningxia Hui Autonomous Region in China. RESULTS: Two types of ST, ST10and ST134, were identified in Ningxia Hui Autonomous Region. Thirty-seven strains belonged to ST10 and 28 strains belonged to ST134. ST134 was a new ST and first found in 2009 and was only widely distributed in Ningxia Hui Autonomous Region at present. The M. bovis ST10 was widely spread in many provinces in China and was widespread in Ningxia Hui Autonomous Region since 2010. It is speculated that the prevalence of M. bovis ST10 in Ningxia Hui Autonomous Region began in 2010. CONCLUSIONS: This study is the first report on the genetic diversity of M. bovis from 2009 to 2018 in Ningxia Hui Autonomous Region and provides the epidemiological information. These results may help further our understanding of the evolution of M. bovis and provide information that may be useful for the development of novel vaccines.


Assuntos
Doenças dos Bovinos/microbiologia , Infecções por Mycoplasma/veterinária , Mycoplasma bovis/genética , Animais , Bovinos , Doenças dos Bovinos/epidemiologia , China/epidemiologia , Variação Genética , Tipagem de Sequências Multilocus/veterinária , Infecções por Mycoplasma/epidemiologia , Reação em Cadeia da Polimerase/veterinária
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