Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 354
Filtrar
1.
J Virol ; : JVI0181121, 2022 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-35044214

RESUMO

We previously reported that hepatitis C virus (HCV) infection activates the reactive oxygen species (ROS)/c-Jun N-terminal kinase (JNK) signaling pathway. However, the roles of ROS/JNK activation in the HCV life cycle still remain unclear. We sought to identify a novel role of ROS/JNK signaling pathway in the HCV life cycle. Immunoblot analysis revealed that HCV-induced ROS/JNK activation promoted phosphorylation of Itch, a HECT-type E3 ubiquitin ligase, leading to activation of Itch. The siRNA-knockdown of Itch significantly reduced the extracellular HCV infectivity titers, HCV RNA, and HCV core protein without affecting intracellular HCV infectivity titers, HCV RNA, and HCV proteins, suggesting that Itch is involved in release of HCV particles. HCV-mediated JNK/Itch activation specifically promoted polyubiquitylation of an AAA-type ATPase VPS4A, but not VPS4B, required to form multivesicular bodies. Site-directed mutagenesis revealed that two lysine residues (K23 and K121) on VPS4A were important for VPS4A polyubiquitylation. The siRNA-knockdown of VPS4A, but not VPS4B, significantly reduced extracellular HCV infectivity titers. Co-immunoprecipitation analysis revealed that HCV infection specifically enhanced the interaction between CHMP1B, a subunit of endosomal sorting complexes required for transport (ESCRT)-III complex, and VPS4A, but not VPS4B, whereas VPS4A K23R/K121R greatly reduced the interaction with CHMP1B. HCV infection significantly increased ATPase activity of VPS4A, but not VPS4A K23R/K121R or VPS4B, suggesting that HCV-mediated polyubiquitylation of VPS4A contributes to activation of VPS4A. Taken together, we propose that HCV-induced ROS/JNK/Itch signaling pathway promotes VPS4A polyubiquitylation, leading to enhanced VPS4A-CHMP1B interaction and promotion of VPS4A ATPase activity, thereby promoting the release of HCV particles. IMPORTANCE ROS/JNK signaling pathway contributes to liver diseases, including steatosis, metabolic disorders, and hepatocellular carcinoma. We previously reported that HCV activates the ROS/JNK signaling pathway, leading to the enhancement of hepatic gluconeogenesis and apoptosis induction. This study further demonstrates that HCV-induced ROS/JNK signaling pathway activates the E3 ubiquitin ligase Itch to promote release of HCV particles via polyubiquitylation of VPS4A. We provide evidence suggesting that HCV infection promotes the ROS/JNK/Itch signaling pathway and ESCRT/VPS4A machinery to release infectious HCV particles. Our results may lead to a better understanding of the mechanistic details of HCV particle release.

2.
Mol Cancer ; 21(1): 16, 2022 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-35031058

RESUMO

BACKGROUND: Gliomas are the most common malignant primary brain tumours with a highly immunosuppressive tumour microenvironment (TME) and poor prognosis. Circular RNAs (circRNA), a newly found type of endogenous noncoding RNA, characterized by high stability, abundance, conservation, have been shown to play an important role in the pathophysiological processes and TME remodelling of various tumours. METHODS: CircRNA sequencing analysis was performed to explore circRNA expression profiles in normal and glioma tissues. The biological function of a novel circRNA, namely, circNEIL3, in glioma development was confirmed both in vitro and in vivo. Mechanistically, RNA pull-down, mass spectrum, RNA immunoprecipitation (RIP), luciferase reporter, and co-immunoprecipitation assays were conducted. RESULTS: We identified circNEIL3, which could be cyclized by EWS RNA-binding protein 1(EWSR1), to be upregulated in glioma tissues and to correlate positively with glioma malignant progression. Functionally, we confirmed that circNEIL3 promotes tumorigenesis and carcinogenic progression of glioma in vitro and in vivo. Mechanistically, circNEIL3 stabilizes IGF2BP3 (insulin-like growth factor 2 mRNA binding protein 3) protein, a known oncogenic protein, by preventing HECTD4-mediated ubiquitination. Moreover, circNEIL3 overexpression glioma cells drives macrophage infiltration into the tumour microenvironment (TME). Finally, circNEIL3 is packaged into exosomes by hnRNPA2B1 and transmitted to infiltrated tumour associated macrophages (TAMs), enabling them to acquire immunosuppressive properties by stabilizing IGF2BP3 and in turn promoting glioma progression. CONCLUSIONS: This work reveals that circNEIL3 plays a nonnegligible multifaceted role in promoting gliomagenesis, malignant progression and macrophage tumour-promoting phenotypes polarization, highlighting that circNEIL3 is a potential prognostic biomarker and therapeutic target in glioma.

3.
J Healthc Eng ; 2022: 8745722, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35028126

RESUMO

Allergic dermatitis (AD) is a common and burdensome inflammatory skin disease, and diagnosis is challenging. This study was conducted to identify candidate genes for AD diagnosis and underlying molecular mechanisms. Gene expression profiles were obtained from datasets GSE121212, GSE130588, and GSE157194. Use differential analysis to identify differentially expressed genes (DEGs) between AD and control. Use enrichment analysis to identify potential molecular dysregulation mechanisms. Comprehensive least absolute shrinkage and selection operator (LASSO) logistic regression, receiver operator characteristic (ROC) curve, and logistic regression analysis are used to identify candidate genes. In addition, ssGSEA and ImmPort database were used to identify AD-related immune response abnormalities. In this study, a total of 60 common genes were identified. Enrichment analysis found that these genes are mainly involved in Th17 cell immune and complement and coagulation cascades. LASSO regression analysis identified 18 feature genes, and screened genes with AUC >0.75 were selected as candidate genes. Finally, PLA2G4D, IFI6, AGR3, IGFL1, SPRR3, ATP13A5, SERPINB13, KRT16, HAS3, and CH25H were recognized as candidate genes and may be able to diagnose AD. PLA2G4D, CH25H, and IFI6 may be risk factors for AD based on logistic analysis. Furthermore, we identified the abnormalities of immune response activation in AD patients. Interestingly, PLA2G4D, CH25H, and IFI6 had positive correlations with immune cells and signaling pathways. PLA2G4D, CH25H, and IFI6 may be candidate diagnostic genes for AD. This may be related to their promotion of abnormal immune activation, especially Th17 cell immune.

4.
J Hazard Mater ; 423(Pt B): 127219, 2022 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-34844349

RESUMO

Herein, novel magnetic nickel incorporated carbon nanofibers (Ni@CNF) were successfully synthesized via electrostatic spinning method for sulfadiazine (SDZ) adsorption. We combined computational and experimental tools to clarify the distinct nature of SDZ on Ni@CNF. Extensive computations and characterizations of SDZ-Ni adsorption complexes evidenced that Ni atoms were indispensable for SDZ adsorption and increasing the number of Ni atoms in Ni@CNF significantly improved SDZ adsorption due to the lower adsorption energy (Ead). As we surmised, the adsorption capacity of Ni@CNF enhanced gradually with increasing the mass ratio of Ni in the composite. The as-prepared 9%Ni@CNF achieved removal efficiency of 98.9% for SDZ (2.5 mg/L) in 25 min, while the pure CNF hardly removed any SDZ under the identical conditions. The experimental data was better fitted by the Langmuir model with the maximum monolayer adsorption capacity of 103.21 mg/g at 318 K. Besides, the 9%Ni@CNF exhibited great applicability to various organic contaminants, and excellent stability and reusability over five consecutive cycles. Overall, for the first time, we provide the evidence that Ni atoms in the Ni@CNF plays a crucial role in SDZ adsorption, which can guide us for constructing nickle incorporated adsorbents with impressive adsorption capacity in environmental remediation.

5.
Front Cell Infect Microbiol ; 11: 796664, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34926330

RESUMO

Lysosome incorporate and degrade proteins in a process known as autophagy. There are three types of autophagy; macroautophagy, microautophagy, and chaperone-mediated autophagy (CMA). Although autophagy is considered a nonselective degradation process, CMA is known as a selective degradation pathway. All proteins internalized in the lysosome via CMA contain a pentapeptide KFERQ-motif, also known as a CMA-targeting motif, which is necessary for selectivity. CMA directly delivers a substrate protein into the lysosome lumen using the cytosolic chaperone HSC70 and the lysosomal receptor LAMP-2A for degradation. Hepatitis C virus (HCV) NS5A protein interacts with hepatocyte-nuclear factor 1α (HNF-1α) together with HSC70 and promotes the lysosomal degradation of HNF-1α via CMA, resulting in HCV-induced pathogenesis. HCV NS5A promotes recruitment of HSC70 to the substrate protein HNF-1α. HCV NS5A plays a crucial role in HCV-induced CMA. Further investigations of HCV NS5A-interacting proteins containing CMA-targeting motifs may help to elucidate HCV-induced pathogenesis.

6.
Sci Total Environ ; : 151904, 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34838558

RESUMO

Preferable biocarrier is vital for start-up and operation of moving bed biofilm reactor (MBBR). Effects of three separate biocarriers - PPC, PU, and PP on MBBRs were systematically investigated including nutrients removal performances, biomass attachment, microbial community, and relevant functional genes. Results showed that three biocarriers achieved similar removal efficiencies for chemical oxygen demand (COD) and total phosphorus (TP), though much higher biomasses were found attached onto PPC and PU carriers. PPC and PU performed better than PP for ammonia nitrogen (NH4+-N) removal. However, PPC exhibited the greatest and most reliable denitrifying efficiency, mainly due to stronger simultaneous nitrification and denitrification during better micro-anoxic-environment created within PPC carriers than others. Further studies by 16S rRNA gene and metagenomic sequencing analysis uncovered the bacterial diversity and structures, and relevant functional genes for nitrogen-transformation and pathways of nitrogen metabolisms, which laid the biological basis for the best performances via biocarrier PPC. This study inspired a feasible approach for municipal wastewater treatment through PPC filled MBBR.

7.
Chemosphere ; : 132731, 2021 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-34743802

RESUMO

Halonitromethanes (HNMs) is a typical class of nitrogenous disinfection byproducts with high toxicity. The effect of Br- on the formation and transformation of HNMs from dimethylamine (DMA) during the ultraviolet (UV)/chlorine disinfection has been investigated in current study. Results reveal that only chloronitromethane, dichloronitromethane and trichloronitromethane (TCNM) could be found during the UV/chlorine disinfection. Whereas in the presence of Br-, nine species of HNMs could be observed simultaneously. When Br- concentration increased from 0 to 15.0 mg L-1, the predominant species of HNMs were gradually changed from TCNM to dibromonitromethane and tribromonitromethane, which contributed to 23.37% and 31.07% of total HNMs concentration at 15 mg L-1 Br-, respectively. The presence of Br- not only shifted the chlorinated-HNMs (Cl-HNMs) towards brominated-HNMs (Br-HNMs) but also affected the dominant species and total concentration of HNMs. When Br- concentration was 4.0 mg L-1, the formation of HNMs decreased with the increase of pH from 6.0 to 8.0 and increased with the increase of free chlorine and DMA. When free chlorine concentration rose from 0.25 to 1.1 mmol L-1, Br-HNMs were shifted to Br(Cl)-HNMs and then to Cl-HNMs. According to the findings, possible formation and transformation pathways of HNMs from DMA were proposed in the presence of Br- during the UV/chlorine disinfection. Finally, it was proved that the effect of Br- on the trend of HNMs in real water was similar to that in deionized water, but higher HNMs concentrations and delayed peak time were observed in real water. This study can provide the scientific evidence and fundamental data for the applications of UV/chlorine disinfection in the treatment of water containing Br-.

8.
Kobe J Med Sci ; 67(2): E38-E47, 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34795154

RESUMO

We previously reported that hepatitis C virus (HCV) NS5A (1b, Con1) protein accepts covalent ISG15 conjugation at specific lysine (Lys) residues (K44, K68, K166, K215 and K308), exhibiting proviral effects on HCV RNA replication. Here we investigated a role of NS5A-ISGylation via Lys residues in HCV propagation using HCV infectious clone. The alignment of amino acid sequences revealed that 5 Lys residues (K20, K26, K44, K139, and K166) of the 13 Lys residues within NS5A (genotype 2a, JFH1 strain) were conserved compared to those of HCV (genotype 1b, Con1 strain). The cell-based ISGylation assay revealed that the K26 residue in the amphipathic helix (AH) domain and the K139 residue in domain I of NS5A (2a, JFH1) had the potential to accept ISGylation. Use of the HCV replicon carrying luciferase gene revealed that the K26 residue but not K139 residue of NS5A (2a, JFH1) was important for HCV RNA replication. Furthermore, cell culture HCV revealed that the mutation with the K26 residue in combination with K139 or K166 on NS5A (2a, JFH1) resulted in complete abolishment of viral propagation, suggesting that the K26 residue collaborates with either the K139 residue or K166 residue for efficient HCV propagation. Taken together, these results suggest that HCV NS5A protein has the potential to accept ISGylation via specific Lys residues, involving efficient viral propagation in a genotype-specific manner.

9.
Polymers (Basel) ; 13(21)2021 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-34771340

RESUMO

Modeling and simulation of the morphology evolution of immiscible polymer blends during injection molding is crucial for predicting and tailoring the products' performance. This paper reviews the state-of-the-art progress in the multiscale modeling and simulation of injection molding of polymer blends. Technological development of the injection molding simulation on a macroscale was surveyed in detail. The aspects of various models for morphology evolution on a mesoscale during injection molding were discussed. The current scale-bridging strategies between macroscopic mold-filling flow and mesoscopic morphology evolution, as well as the pros and cons of the solutions, were analyzed and compared. Finally, a comprehensive summary of the above models is presented, along with the outlook for future research in this field.

10.
Artigo em Inglês | MEDLINE | ID: mdl-34775879

RESUMO

The shape of skin flaps is only described by swatches for preoperative design because of the irregular shape of skin wounds caused by trauma in the clinic. The method is rough, and the flaps cut often cannot match the wounds and affect their appearance. Computer-aided design technology helps to attain precise results in less time. This study proposes a skin wound morphological flattening algorithm based on hierarchical values. First, the skin wound is scanned by three-dimensional (3D) scanning technology to obtain a spatial mesh model consisting of triangular cells, and the mesh model is layered with a hierarchical value. Then, the layered mesh is topologically mapped to the plane. Subsequently, the stress and strain of the skin are simulated using a mechanical method, and the shape of the flattened skin wound is optimized layer by layer. Finally, the multiresolution smoothing technique is used to smooth the developed boundary contour and fit the curve to obtain a guidance plan for preoperative flap design. The results of the study showed that this method can accurately determine the shape of the skin wounds and quantitatively analyze the preoperative design results of the skin flaps. The average error of the area and edge length after flattening was reduced to less than 10%. The work is designed to realize the precise and individualized design of flap schemes before operation and to help standardize the preoperative design process.

12.
Front Cell Dev Biol ; 9: 729211, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34621746

RESUMO

Background: Triple-negative breast cancer (TNBC) is the most invasive and metastatic subtype of breast cancer. SUMO1-activating enzyme subunit 1 (SAE1), an E1-activating enzyme, is indispensable for protein SUMOylation. SAE1 has been found to be a relevant biomarker for progression and prognosis in several tumor types. However, the role of SAE1 in TNBC remains to be elucidated. Methods: In the research, the mRNA expression of SAE1 was analyzed via the cancer genome atlas (TCGA) and gene expression omnibus (GEO) database. Cistrome DB Toolkit was used to predict which transcription factors (TFs) are most likely to increase SAE1 expression in TNBC. The correlation between the expression of SAE1 and the methylation of SAE1 or quantity of tumor-infiltrating immune cells was further invested. Single-cell analysis, using CancerSEA, was performed to query which functional states are associated with SAE1 in different cancers in breast cancer at the single-cell level. Next, weighted gene coexpression network (WGCNA) was applied to reveal the highly correlated genes and coexpression networks of SAE1 in TNBC patients, and a prognostic model containing SAE1 and correlated genes was constructed. Finally, we also examined SAE1 protein expression of 207 TNBC tissues using immunohistochemical (IHC) staining. Results: The mRNA and protein expression of SAE1 were increased in TNBC tissues compared with adjacent normal tissues, and the protein expression of SAE1 was significantly associated with overall survival (OS) and disease-free survival (DFS). Correlation analyses revealed that SAE1 expression was positively correlated with forkhead box M1 (FOXM1) TFs and negatively correlated with SAE1 methylation site (cg14042711) level. WGCNA indicated that the genes coexpressed with SAE1 belonged to the green module containing 1,176 genes. Through pathway enrichment analysis of the module, 1,176 genes were found enriched in cell cycle and DNA repair. Single-cell analysis indicated that SAE1 and its coexpression genes were associated with cell cycle, DNA damage, DNA repair, and cell proliferation. Using the LASSO COX regression, a prognostic model including SAE1 and polo-like kinase 1 (PLK1) was built to accurately predict the likelihood of DFS in TNBC patients. Conclusion: In conclusion, we comprehensively analyzed the mRNA and protein expression, prognosis, and interaction genes of SAE1 in TNBC and constructed a prognostic model including SAE1 and PLK1. These results might be important for better understanding of the role of SAE1 in TNBC. In addition, DNA methyltransferase and TFs inhibitor treatments targeting SAE1 might improve the survival of TNBC patients.

13.
Transpl Immunol ; 69: 101476, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34601097

RESUMO

BACKGROUND: ABO-incompatible liver transplantation (ABOi-LT) is increasingly used to overcome donor shortage. Evidence about disadvantage and advantage in comparison with ABO-compatible liver transplantation (ABOc-LT) needs to be performed in the early and late periods. Herein, We compared the short-term and long-term outcomes between ABOi-LT and ABOc-LT cohorts. METHODS: We performed a meta-analysis based on the observation studies which included outcomes at ≥1 year after ABOi-LT and ABOc-LT procedures, based on the MEDLINE (via Pubmed), the Cochrance Central Register of Controlled Trials (CENTRAL), and EMBASE (via Ovid) systems. Two researchers independently screened each study according to the pre-established inclusion and exclusion criteria to assess the quality of each study and extracted data from published studies. The primary outcome indicators were all-cause mortality and graft survival at 1, 3 and 5 years after transplantation. In the meta-analysis, we based on the value of heterogeneity using a fixed-effect and a random-effect. A fixed-effect model was used if the value of I2 was less than or equal 50%; and a random-effect model was used if the value of I2 was greater than 50%. FINDINGS: Out of 335 identified records, 29 records with 10,783 patients with liver transplants; 2137 of them were ABOi-LTs and the remaining 8646 were ABOc-LTs. There was no significant difference at 1-year, 3-year, and 5-year in all-cause mortality, death-censored graft survival and complication incidence rate between ABO-incompatible living donor liver transplantation (ABOi-LDLT) group and ABO-compatible living donor liver transplantation (ABOc-LDLT) group. Compared with ABO-compatible deceased donor liver transplantation (ABOc-DDLT), ABO-incompatible deceased donor liver transplantation (ABOi-DDLT) had a higher 1-year all-cause mortality, and the value of totally pooled odds ratio (OR) was 1.89 (1.28,2.80). However, there was no significant difference at 3-year and 5-year all-cause mortality between ABOi-DDLT and ABOc-DDLT groups. ABOi-DDLT group had a lower 1-year and 5-year death-censored graft survival than ABOc-DDLT, as the value of totally pooled OR was 1.91 (1.41,2.60) and 1.52 (1.12,2.05), respectively. No significant difference was detected at 3-year death-censored graft survival between ABOi-DDLT and ABOc-DDLT groups. ABOi-DDLT group had a higher complication incidence rate than ABOc-DDLT, and the value of totally pooled OR was 2.26 (1.53,3.33). We found no obvious bias except for the complication of living donor liver transplantation (LDLT; P = 0.038). IN CONCLUSION: The short-term and long-term outcomes were worse after ABOi-DDLT than ABOc-DDLT in the all-cause mortality, death-censored graft survival, and complication incidence rate. However, the same outcomes were essentially comparable between ABOi-LDLT vs. ABOc-LDLT cohorts. Considering the current shortage of liver donors, we believe that ABOi-LT from living donor and deceased donors can save lives under emergency situations.

14.
J Gen Virol ; 102(10)2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34661519

RESUMO

Ubiquitin and ubiquitin-like protein modification play important roles in modulating the functions of viral proteins in many viruses. Here we demonstrate that hepatitis B virus (HBV) X protein (HBx) is modified by ISG15, which is a type I IFN-inducible, ubiquitin-like protein; this modification is called ISGylation. Immunoblot analyses revealed that HBx proteins derived from four different HBV genotypes accepted ISGylation in cultured cells. Site-directed mutagenesis revealed that three lysine residues (K91, K95 and K140) on the HBx protein, which are well conserved among all the HBV genotypes, are involved in acceptance of ISGylation. Using expression plasmids encoding three known E3 ligases involved in the ISGylation to different substrates, we found that HERC5 functions as an E3 ligase for HBx-ISGylation. Treatment with type I and type III IFNs resulted in the limited suppression of HBV replication in Hep38.7-Tet cells. When cells were treated with IFN-α, silencing of ISG15 resulted in a marked reduction of HBV replication in Hep38.7-Tet cells, suggesting a role of ISG15 in the resistance to IFN-α. In contrast, the silencing of USP18 (an ISG15 de-conjugating enzyme) increased the HBV replication in Hep38.7-Tet cells. Taken together, these results suggest that the HERC5-mediated ISGylation of HBx protein confers pro-viral functions on HBV replication and participates in the resistance to IFN-α-mediated antiviral activity.


Assuntos
Citocinas/metabolismo , Vírus da Hepatite B/fisiologia , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Transativadores/metabolismo , Ubiquitinas/metabolismo , Proteínas Virais Reguladoras e Acessórias/metabolismo , Replicação Viral , Linhagem Celular , Farmacorresistência Viral , Vírus da Hepatite B/genética , Humanos , Interferon-alfa/farmacologia , Interferon beta/farmacologia , Interferons/farmacologia , Transativadores/química , Ubiquitina Tiolesterase/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Proteínas Virais Reguladoras e Acessórias/química
15.
Signal Transduct Target Ther ; 6(1): 355, 2021 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-34650034

RESUMO

This multicenter phase-II trial aimed to investigate the efficacy, safety, and predictive biomarkers of toripalimab plus chemotherapy as second-line treatment in patients with EGFR-mutant-advanced NSCLC. Patients who failed from first-line EGFR-TKIs and did not harbor T790M mutation were enrolled. Toripalimab plus carboplatin and pemetrexed were administrated every three weeks for up to six cycles, followed by the maintenance of toripalimab and pemetrexed. The primary endpoint was objective-response rate (ORR). Integrated biomarker analysis of PD-L1 expression, tumor mutational burden (TMB), CD8 + tumor-infiltrating lymphocyte (TIL) density, whole-exome, and transcriptome sequencing on tumor biopsies were also conducted. Forty patients were enrolled with an overall ORR of 50.0% and disease-control rate (DCR) of 87.5%. The median progression free survival (PFS) and overall survival were 7.0 and 23.5 months, respectively. The most common treatment-related adverse effects were leukopenia, neutropenia, anemia, ALT/AST elevation, and nausea. Biomarker analysis showed that none of PD-L1 expression, TMB level, and CD8 + TIL density could serve as a predictive biomarker. Integrated analysis of whole-exome and transcriptome sequencing data revealed that patients with DSPP mutation had a decreased M2 macrophage infiltration and associated with longer PFS than those of wild type. Toripalimab plus chemotherapy showed a promising anti-tumor activity with acceptable safety profiles as the second-line setting in patients with EGFR-mutant NSCLC. DSPP mutation might serve as a potential biomarker for this combination. A phase-III trial to compare toripalimab versus placebo in combination with chemotherapy in this setting is ongoing (NCT03924050).

16.
Yi Chuan ; 43(9): 849-857, 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34702698

RESUMO

MicroRNAs (miRNAs), a family of endogenous non-coding RNAs with a length of about 22 nucleotides, are widely found in eukaryotes. miRNAs can affect gene expression through specific bindings with mRNAs of target genes and participate in the regulation of a variety of biological processes. Giant panda is not only a unique rare animal in China, but also the focus of attention on wildlife preservation worldwide. In recent years, with the popularization of next-generation sequencing (NGS) technology, miRNAs in giant panda have been discovered and identified one after another. In this review, we focus on the research progress on miRNAs in giant panda, involved in immune response, mammary gland development, sperm freezing tolerance and other biological processes, and then discuss future research directions of miRNAs in giant panda, and thus providing the scientific references and new ideas for studying the regulatory mechanisms of miRNAs and promoting the breeding and protection of giant panda.


Assuntos
MicroRNAs , Ursidae , Animais , China , Masculino , MicroRNAs/genética , RNA Mensageiro , Espermatozoides , Ursidae/genética
17.
ACS Nano ; 15(10): 15874-15891, 2021 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-34586802

RESUMO

The clinical application of small interfering RNA (siRNA) drugs provides promising opportunities to develop treatment strategies for autoimmune inflammatory diseases. In this study, siRNAs targeting the endoplasmic reticulum to nucleus signaling 1 (ERN1) gene (siERN1) were screened. Two cationic polymers, polyethylenimine (PEI) and poly(ß-amino amine) (PBAA), which can improve the efficiency of the siRNA transfection, were used as siERN1 delivery carriers. They were implemented to construct a nanodrug delivery system with macrophage-targeting ability and dual responsiveness for the treatment of autoimmune inflammatory diseases. In terms of the mechanism, siERN1 can regulate the intracellular calcium ion concentration by interfering with the function of inositol 1,4,5-trisphosphate receptor 1/3 (IP3R1/3) and thus inducing M2 polarization of macrophages. Furthermore, siERN1-nanoprodrug [FA (folic acid)-PEG-R(RKKRRQRRR)-NPs(ss-PBAA-PEI)@siERN1] acts as a conductor of macrophage polarization by controlling the calcium ion concentration and is an inhibitor of MyD88-dependent Toll-like receptor signaling. The results revealed that the FA-PEG-R-NPs@siERN1 has universal biocompatibility, long-term drug release responsiveness, superior targeting properties, and therapeutic effects in mouse collagen-induced arthritis and inflammatory bowel disease models. In conclusion, this study reveals a potential strategy to treat autoimmune inflammatory disorders.


Assuntos
Polietilenoimina , Receptores Toll-Like , Animais , Macrófagos , Camundongos , RNA Interferente Pequeno , Transfecção
18.
Artigo em Inglês | MEDLINE | ID: mdl-34539803

RESUMO

Surgery is now the main clinical treatment for hemorrhoids, and the procedure for prolapse and hemorrhoids (PPH) is the commonly used procedure. The key to evaluating the efficacy of surgery includes the quality of postoperative wound healing and the occurrence of complications, so it is especially important to enhance the postoperative rehabilitation of hemorrhoids. This study investigates the method of postoperative treatment with Kangfuxin solution fumigation bath to explore the role of this method in the efficacy of patients after hemorrhoid PHH surgery and its effect on postoperative complications. It will accumulate some relevant information to improve the efficacy of hemorrhoid surgery and postoperative complications and open new ideas for further postoperative rehabilitation of other diseases in the anal area. A total of 106 patients with hemorrhoids were included in this study, all of whom were treated with PHH surgery. After surgery, they were randomly divided into a control group treated with warm water sitz bath and an observation group treated with Kangfuxin solution fumigation bath, with 53 cases in each group. We observed all patients' postoperative pain, bleeding, and perianal edema on a daily basis after surgery; we recorded the time of wound healing and hospital stay. The maximum anal squeeze pressure (MASP), anal defecation diastole pressure (ADDP), anal resting pressure (ARP), and the length of the high-pressure zone (HPZ) were used as observation indicators to evaluate the anal function of the patients before and after treatment. The results of the evaluation of the efficacy of patients after the treatment period showed that the total effective rate of treatment in the observation group (92.45%) was significantly higher than that of the control group (77.36%). The postoperative recovery showed that the wound healing time, hospitalization time, pain, bleeding, and edema scores at 3 and 5 days after surgery were lower in the observation group than in the control group; MASP and ARP increased in both groups after treatment compared to before treatment, with more increase in the observation group. The results suggest that patients with hemorrhoids after PPH should pay attention to postoperative care and rehabilitation. It also reveals that the application of Kangfuxin solution fumigation treatment has a significant effect, which can effectively reduce the patient's wound healing and hospital stay, while improving the patient's anal function and reducing postoperative complications, and is worthy of clinical promotion and application.

19.
Curr Med Sci ; 41(5): 1029-1036, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34542828

RESUMO

OBJECTIVE: Autosomal dominant polycystic kidney disease (ADPKD) is mainly caused by the pathogenic mutation of PKD1 or PKD2 gene and usually affects bilateral kidneys. Synonymous mutations are generally assumed to be neutral as they do not alter amino acids. Herein, we described an extremely rare ADPKD child caused by a heterozygous synonymous mutation of PKD2 gene accompanied by massive proteinuria and congenital solitary kidney. METHODS: Clinical characteristics of the patients were summarized. Whole-exome sequencing was performed to screen the disease-causing gene mutation, and reverse transcription polymerase chain reaction (RT-PCR) and Sanger sequencing were applied to analyze the impact of the identified mutation on gene transcription and splicing. RESULTS: Polycystic changes were found in the solitary kidney of a girl initially presented with nephrotic-range proteinuria. Thereafter her mother and 2 other family members were diagnosed to be ADPKD. Whole-exome sequencing of the proband identified a heterozygous synonymous mutation (c.1716G>A, p.Lys572=) located in the splicing site of exon 7 in PKD2 gene, which was co-segregated with the PKD phenotype in the family. RT-PCR and direct sequencing of amplified products revealed that this heterozygous synonymous mutation led to exon7 skipping in PKD2 gene. CONCLUSION: We reported an extremely rare child case of ADPKD2 in combination with solitary kidney and nephrotic-range proteinuria, and firstly confirmed the pathogenicity of a heterozygous synonymous mutation (c.1716G>A) in PKD2 gene. The results indicate that synonymous mutations should not be excluded from disease-causing if they are located in splicing site of an exon.

20.
Artigo em Inglês | MEDLINE | ID: mdl-34543211

RESUMO

The combination of Raman spectroscopy and deep learning technology provides an automatic, rapid, and accurate scheme for the clinical diagnosis of pathogenic bacteria. However, the accuracy of existing deep learning methods is still limited because of the single and fixed scales of deep neural networks. We propose a deep neural network that can learn multi-scale features of Raman spectra by using the automatic combination of multi-receptive fields of convolutional layers. This model is based on the expert knowledge that the discrimination information of Raman spectra is composed of multi-scale spectral peaks. We enhance the interpretability of the model by visualizing the activated wavenumbers of the bacterial spectrum that can be used for reference in related work. Compared with existing state-of-the-art methods, the proposed method achieves higher accuracy and efficiency for bacterial identification on isolate-level, empiric-treatment-level, and antibiotic-resistance-level tasks. The clinical bacterial identification task requires significantly fewer patient samples to achieve similar accuracy. Therefore, this method has tremendous potential for the identification of clinical pathogenic bacteria, antibiotic susceptibility testing, and prescription guidance.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...