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1.
Eur J Med Chem ; 219: 113426, 2021 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-33848787

RESUMO

The complex pathogenesis of Alzheimer's disease (AD) has become a major obstacle in its treatment. An effective approach is to develop multifunctional agents that simultaneously target multiple pathological processes. Here, a series of diosgenin-indole compounds were designed, synthesized and evaluated for their neuroprotective effects against H2O2 (hydrogen peroxide), 6-OHDA (6-hydroxydopamine) and Aß (beta amyloid) damages. Preliminary structure-activities relationship revealed that the introduction of indole fragment and electron-donating group at C-5 on ring indole could be beneficial for neuroprotective activities. Results indicated that compound 5b was the most promising candidate against cellular damage induced by H2O2 (52.9 ± 1.9%), 6-OHDA (38.4 ± 2.4%) and Aß1-42 (54.4 ± 2.7%). Molecular docking study suggested the affinity for 5b bound to Aß1-42 was -40.59 kcal/mol, which revealed the strong binding affinity of 5b to Aß1-42. The predicted values of brain/blood partition coefficient (-0.733) and polar surface area (85.118 Å2) indicated the favorable abilities of BBB permeation and absorption of 5b. In addition, 5b significantly decreased ROS (reactive oxygen species) production induced by H2O2. In the following in vivo experiment, 5b obviously attenuated memory and learning impairments of Aß-injected mice. In summary, compound 5b could be considered as a promising dual-functional neuroprotective agent against AD.

2.
Gen Comp Endocrinol ; 307: 113744, 2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33705742

RESUMO

The carnivorous teleost fish is often intolerant to high levels of postprandial plasma glucose. This study aimed to evaluate the effects of insulin-like growth factor-1 (IGF-1) and growth hormone (GH) administrations on plasma glucose levels and expression of glucose transporters (GLUTs) in various tissues of hybrid grouper, and hence to further clarify the hormone-GLUTs-plasma glucose regulating axis. Twenty-four experimental fish (average body weight: 77.5 ± 5.4 g) were selected and injected with recombinant human IGF-1 (0.2 µg/g body weight) and PBS (0.01 mol/L) in enterocoelia, respectively, and in the GH injected experiment, the same quantity of fish (average body weight: 103.8 ± 5.8 g) were administrated with GH at a dose of 0.5 µg/g body weight or with PBS at a dose of 0.01 mol/L. Results showed that plasma glucose level was significantly (P < 0.05) declined by the IGF-1 administration but elevated by the GH administration. Plasma IGF-1 concentration was significantly (P < 0.01) elevated by the IGF-1 administration, while GH concentration did not significantly (P ≥ 0.05) respond to the GH administration. The relative mRNA levels of insulin-like growth factor-1 receptor a (IGF-Ra) in liver and muscle were decreased significantly with the IGF-1 administration, and a similar variation tendency was also found in insulin-like growth factor-1 receptor b (IGF-Rb) in liver, muscle and adipose tissues. Besides, the relative mRNA level of insulin receptor (IRS) in liver was significantly increased in the IGF-1 administrated group. After the GH administration, the mRNA levels of hepatic growth factor receptor 2 (GHR2) and IGF-1 were significantly elevated. As for GLUTs, the relative mRNA levels of GLUT1 and GLUT2 in liver were obviously elevated by the IGF-1 administration, while the mRNA level of GLUT4 in muscle was reduced. In liver, the protein levels of GLUT1, 2 and 4 were significantly elevated by the IGF-1 administration, and in adipose, only GLUT1 was observed to have a significantly increased protein level. The mRNA expression of GLUTs was less affected by the GH administration. The protein level of GLUT1 in liver was significantly reduced by the GH administration, while in adipose, it was significantly increased. The protein level of GLUT2 in liver or adipose showed an opposite variation as that of GLUT1. Overall, IGF-1 had a hypoglycemic effect on hybrid grouper, and this probably was through up-regulating the protein levels of hepatic GLUT1, 2 and 4 and adipose GLUT1. GH showed an opposite role in regulating plasma glucose level as IGF-1.

3.
Parasit Vectors ; 14(1): 159, 2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33726813

RESUMO

BACKGROUND: Culex pipiens (Cx. pipiens) complex, which acts as a vector of viruses and is widespread and abundant worldwide, including West Nile virus, Japanese encephalitis virus, and Sindbis virus, can cause serious vector-borne diseases affecting human health. Unfortunately, mosquitoes have developed deltamethrin resistance because of its long-term overuse, representing a major challenge to mosquito control. Understanding the molecular regulatory mechanisms of resistance is vital to control mosquitoes. MicroRNAs (miRNAs) are short non-coding RNAs that have been demonstrated to be important regulators of gene expression across a wide variety of organisms, which might function in mosquito deltamethrin resistance. In the present study, we aimed to investigate the regulatory functions of miR-4448 and CYP4H31 in the formation of insecticidal resistance in mosquito Culex pipiens pallens. METHODS: We used quantitative real-time reverse transcription PCR to measure miR-4448 and CYP4H31 (encoding a cytochrome P450) expression levels. The regulatory functions of miR-4448 and CYP4H31 were assessed using dual-luciferase reporter assays. Then, oral feeding, RNA interference, and the American Centers for Disease Control and Prevention bottle bioassay were used to determine miR-4448's association with deltamethrin resistance by targeting CYP4H31 in vivo. Cell Counting Kit-8 (CCK-8) was also used to detect the viability of pIB/V5-His-CYP4H31-transfected C6/36 cells after deltamethrin treatment in vitro. RESULTS: MiR-4448 was downregulated in the deltamethrin-resistant strain (DR strain), whereas CYP4H31 was downregulated in deltamethrin-susceptible strain. CYP4H31 expression was downregulated by miR-4448 recognizing and binding to its 3' untranslated region. Functional verification experiments showed that miR-4448 overexpression resulted in lower expression of CYP4H31. The mortality of miR-4448 mimic-injected DR strain mosquitoes was higher than that of the controls. CCK-8 assays showed that CYP4H31 decreased cellular resistance to deltamethrin in vitro and the mortality of the DR strain increased when CYP4H31 was knocked down in vivo. CONCLUSIONS: In mosquitoes, miR-4448 participates in deltamethrin resistance by targeting CYP4H31. The results of the present study increase our understanding of deltamethrin resistance mechanisms.

4.
Int J Biol Macromol ; 179: 475-484, 2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33675837

RESUMO

Many Chinese herbs are well known for their neuroprotective and anti-oxidant properties. Extracts of Salvia miltiorrhiza and Anemarrhenae asphodeloides, tanshinone IIA (tanIIA), salvianolic acid B (Sal B) and sarsasapogenin (ML-1), were selected to study their dissociation potential towards Aß42 peptide fibrils and neuroprotective effect on cells. Moreover, derivatives of sarsasapogenin (ML-2, ML-3 and ML-4) have been prepared by the addition of modified carbamate moiety. TanIIA and Sal B have shown to possess a strong ability to dissociate Aß42 fibrils. The dissociation potential of ML-1 increased upon the introduction of carbamate moiety with N-heterocycles. In silico data revealed that derivatives ML-4 and Sal B interact with Aß42 regions responsible for fibril stabilization through hydrogen bonds. Contrary, tanIIA binds close to a central hydrophobic region, which may lead to destabilization of fibrils. Sarsasapogenin derivative ML-2 decreased nitride oxide production, and derivative ML-4 enhanced the growth of neurites. The reported data highlight the possibility of using active compounds to design novel treatment agents for Alzheimer's disease.

5.
Bioorg Med Chem ; 37: 116109, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33780813

RESUMO

A novel series of multitargeted molecules were designed and synthesized by combining the pharmacological role of cholinesterase inhibitor and antioxidant of steroid as potential ligands for the treatment of Vascular Dementia (VD). The oxygen-glucose deprivation (OGD) model was used to evaluate these molecules, among which the most potent compound ML5 showed the highest activity. Firstly, ML5 showed appropriate inhibition of cholinesterases (ChEs) at orally 15 mg/kg in vivo. The further test revealed that ML5 promoted the nuclear translocation of Nrf2. Furthermore, ML5 has significant neuroprotective effect in vivo model of bilateral common carotid artery occlusion (BCCAO), significantly increasing the expression of Nrf2 protein in the cerebral cortex. In the molecular docking research, we predicted the ML5 combined with hAChE and Keap1. Finally, compound ML5 displayed normal oral absorption and it was nontoxic at 500 mg/kg, po, dose. We can draw the conclusion that ML5 could be considered as a new potential compound for VD treatment.

6.
Protein Expr Purif ; 182: 105844, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33592251

RESUMO

The human autophagy-related protein ATG7 (hATG7), an E1-like ubiquitin enzyme, activates two ubiquitin-like proteins, LC3 (Atg8) and Atg12, and promotes autophagosome formation. While hATG7 plays an essential role for the autophagy conjugation system, the production of full-length functional hATG7 in bacterial systems remains challenging. Previous studies have demonstrated that the HIV-1 virus-encoded Tat peptide ('GRKKRRQRRR') can increase the yield and solubility of heterologous proteins. Here, functional full-length hATG7 was expressed using the pET28b-Tat expression vector in the Escherichia coli BL21 (DE3) strain. Recombinant hATG7 protein aggregated as inclusion bodies while expressed with widely used prokaryotic expression plasmids. In contrast, the solubility of Tat-tagged hATG7 increased significantly with prolonged time compared to Tat-free hATG7. The recombinant proteins were purified to >90% homogeneity under native conditions with a single step of affinity chromatography purification. The results of in vitro pull-down and LC3B-I lipidation assays showed that Tat-tagged hATG7 directly interacted with LC3B-I and promoted LC3B-I lipidation, suggesting that Tat-tagged hATG7 has significant catalytic activity. Overall, this study provides a novel method for improving the functional expression of full-length hATG7 in bacterial systems by fusion with the Tat peptide, a process which may be applied in future studies of hATG7 structure and function.

7.
Sci Rep ; 11(1): 2883, 2021 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-33558592

RESUMO

For the purpose of assessing the radiation dose of the victims involved in the nuclear emergency or radiation accident, a new type of X-band EPR resonant cavity for in vivo fingernail EPR dosimetry was designed and a homemade EPR spectrometer for in vivo fingernail detection was constructed. The microwave resonant mode of the cavity was rectangular TE101, and there was a narrow aperture for fingernail detection opened on the cavity's wall at the position of high detection sensitivity. The DPPH dot sample and the fingernail samples were measured based on the in vivo fingernail EPR spectrometer. The measurements of the DPPH dot sample verified the preliminary functional applicable of the EPR spectrometer and illustrated the microwave power and modulation response features. The fingernails after irradiation by gamma-ray were measured and the radiation-induced signal was acquired. The results indicated that the cavity and the in vivo EPR dosimeter instrument was able to detect the radiation-induced signal in irradiated fingernail, and preliminarily verified the basic function of the instrument and its potential for emergency dose estimate after a radiation accident.

8.
Int Wound J ; 2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33580604

RESUMO

We designed this retrospective study with aims to investigate the incidence and risk factors associated with surgical site infection (SSI) following posterior lumbar interbody fusion (PLIF) and instrumentation in patients with lumbar degenerative disease. Eligible patients treated between January 2016 and June 2019 were included. Electronic medical records were inquired for data extraction and collection. Patients with SSI and without SSI were compared using the univariate analyses, and the association between variables and risk of SSI was investigated using multivariate logistics regression analyses. Among 1269 patients, 43 were found to have SSI, indicating a rate of 3.4%. Microbiological culture tests showed 88.4% patients had a positive result. Four SSIs were caused by mixed bacterial, and the remaining 34 by single bacteria. Multiple drug-resistant strains were detected in 25 (65.8%) SSIs, with meticillin-resistant coagulase-negative staphylococcus (MRCNS) predominating (12, 48.0%). ASA III and above (odd ratio (OR), 1.67; 95% confidence interval (CI), 1.11 to 3.07), preoperative stay (OR, 1.13; 95% CI, 1.04 to 1.23), heart disease (OR, 2.88; 95% CI, 1.24 to 6.71), diabetes mellitus (OR, 3.28; 95% CI, 1.66 to 6.47) and renal insufficiency (OR, 4.23; 95% CI, 1.26 to 10.21), prolonged prophylactic antibiotics use (OR, 4.43; 95% CI, 2.30 to 8.54), and the reduced lymphocyte count (OR, 2.11; 95% CI, 1.03 to 4.33) were identified as independent risk factors associated with SSI. These factors, although most not modifiable, should be kept in mind, optimised for surgical conditions, or readily adjusted in the future postoperative management of antibiotics, to reduce postoperative SSIs.

9.
J Med Entomol ; 2021 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-33590868

RESUMO

The wide distribution of Culex (Cx.) pipiens complex mosquitoes makes it difficult to prevent the transmission of mosquito-borne diseases in humans. Gene editing using CRISPR/Cas9 is an effective technique with the potential to solve the growing problem of mosquito-borne diseases. This study uses the ReMOT Control technique in Culex pipiens pallens (L.) to produce genetically modified mosquitoes. A microinjection system was established by injecting 60 adult female mosquitoes-14 µl injection mixture was required, and no precipitation occurred with ≤1 µl of endosomal release reagents (chloroquine or saponin). The efficiency of delivery of the P2C-enhanced green fluorescent protein-Cas9 (P2C-EGFP-Cas9) ribonucleoprotein complex into the ovary was 100% when injected at 24 h post-bloodmeal (the peak of vitellogenesis). Using this method for KMO knockout, we found that gene editing in the ovary could also occur when P2C-Cas9 RNP complex was injected into the hemolymph of adult Cx. pipiens pallens by ReMOT Control. In the chloroquine group, of the 2,251 G0 progeny screened, 9 individuals showed with white and mosaic eye phenotypes. In the saponin group, of the 2,462 G0 progeny screened, 8 mutant individuals were observed. Sequencing results showed 13 bp deletions, further confirming the fact that gene editing occurred. In conclusion, the successful application of ReMOT Control in Cx. pipiens pallens not only provides the basic parameters (injection parameters and injection time) for this method but also facilitates the study of mosquito biology and control.

10.
Carbohydr Polym ; 258: 117708, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33593577

RESUMO

Lytic polysaccharide monooxygenases (LPMOs) are attracting much attention for their potential application in biodegradation. However, there are limited studies on the characterization of the AA11 family. Here, a novel AA11 family protein, TgAA11, from Trichoderma guizhouense NJAU 4742 was characterized, and the isothermal titration calorimetry (ITC) analysis results showed that it exhibited tight binding capacity for copper ions with a Kd value of 4.83 ± 0.79 µM. The MALDI-TOF-MS analysis results indicated that TgAA11 could act on ß-chitin to form C1 oxidation products, and some deacetylated chitooligosaccharides. In addition, the degradation of α-chitin and ß-chitin by a chitinolytic enzyme Sg-chi was substantially increased in the presence of TgAA11 by 39.9 % and 288.2 %, respectively. Furthermore, the active site residues predicted showed that His61 and Tyr142 might be critical for the active site residues of the TgAA11 protein. This study will contribute to the understanding of the function of AA11 LPMOs in the degradation of chitin.

12.
Food Funct ; 12(3): 1219-1231, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33432954

RESUMO

Caffeic acid (CA), a derivative of cinnamic acid, exists in various vegetables and fruits. Natural compounds as beneficial antioxidants play an important role in the research of Alzheimer's disease (AD). In this study, we evaluated the effects of CA against AD using the C. elegans models of AD. We found that CA significantly alleviated Aß-induced toxicity, increased lifespan, decreased body paralysis, and improved reproductive defects. Also, CA treatment increased resistance to heat and oxidative stress in N2 and CL4176. Moreover, reactive oxygen species (ROS) levels and polyglutamine (polyQ40) aggregate formation were reduced. Furthermore, the mechanistic studies revealed that CA activated transcription factor DAF-16 and its downstream targets SOD-3 and GST-4 to protect against Aß toxicity. Also, the heat shock proteins hsf-1 and hsp-16.2 mRNA were up-regulated in CL4176. Moreover, CA activated the mRNA expression of lgg-1. Lastly, the KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis of RNA-seq data revealed that there was a significant change in the metabolism-related pathways. Overall, these results suggested an underlying mechanism of action of CA in treating AD at an organism level.

13.
Artigo em Inglês | MEDLINE | ID: mdl-33497345

RESUMO

Orthognathic surgical outcomes rely heavily on the quality of surgical planning. Automatic estimation of a reference facial bone shape significantly reduces experience-dependent variability and improves planning accuracy and efficiency. We propose an end-to-end deep learning framework to estimate patient-specific reference bony shape models for patients with orthognathic deformities. Specifically, we apply a point-cloud network to learn a vertex-wise deformation field from a patients deformed bony shape, represented as a point cloud. The estimated deformation field is then used to correct the deformed bony shape to output a patient-specific reference bony surface model. To train our network effectively, we introduce a simulation strategy to synthesize deformed bones from any given normal bone, producing a relatively large and diverse dataset of shapes for training. Our method was evaluated using both synthetic and real patient data. Experimental results show that our framework estimates realistic reference bony shape models for patients with varying deformities. The performance of our method is consistently better than an existing method and several deep point-cloud networks. Our end-to-end estimation framework based on geometric deep learning shows great potential for improving clinical workflows.

14.
In Vivo ; 35(1): 275-281, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33402474

RESUMO

BACKGROUND/AIM: We investigated pelvic arterial deformation and shift due to intraoperative pneumoperitoneum and postural changes in an animal model. MATERIALS AND METHODS: Computed tomography images of pigs were acquired in different body positions (supine, head down at 5° and 10°, right lateral recumbent at 5° and 15°) before and after insufflation. We used a free software (3D Slicer) for image analysis. After landmark registration using 10 markers inserted into the pelvis, pelvic arterial deformation and shift of seven arterial bifurcation points were evaluated. The distance moved was the target registration error (TRE) from the points registered in the supine position. Fiducial registration error (FRE) was measured using the 10 pelvic markers. RESULTS: TRE average from postural changes ranged from 0.7 to 1.2 mm and was 1.4 mm due to pneumoperitoneum. TRE and FRE averages were 2.1 mm and 0.2 mm, respectively. CONCLUSION: The pelvis was useful for registering anatomical landmarks.

15.
Cell Prolif ; 54(3): e12981, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33458917

RESUMO

OBJECTIVES: Circular RNAs (circRNAs) are essential participants in tumour progression. This study focused on investigating the mechanism of a novel functional circRNA in gastric cancer (GC). METHODS: Gene expression was detected by qRT-PCR or Western blot. Survival curves were generated via Kaplan-Meier method. In vitro and in vivo assays were used to investigate the impact of circ_SMAD4 on GC cell growth and tumorigenesis. Agarose gel electrophoresis assay, RNase R treatment and Sanger sequencing were utilized for confirming the circular structure of circ_SMAD4. Relationship between molecules was monitored by a series of mechanical experiments, as needed. RESULTS: Circ_SMAD4 expression was potentiated in GC. Circ_SMAD4 depletion impeded GC cell growth in vitro and restrained tumorigenesis in vivo. Mechanically, nuclear circ_SMAD4 recruited TCF4 to facilitate CTNNB1 transcription, while cytoplasmic circ_SMAD4 sequestered miR-1276 to prevent the silence of CTNNB1 mRNA, leading to activation of Wnt/ß-catenin pathway. Rescue experiments validated that circ_SMAD4 depended on miR-1276/TCF4-regulated CTNNB1 to elicit accelerating effects on GC cell growth. CONCLUSION: Circ_SMAD4 facilitated GC tumorigenesis by activating CTNNB1-dependent Wnt/ß-catenin pathway. Hopefully, the findings could provide new clues for improving GC prognosis and treatment.


Assuntos
Transformação Celular Neoplásica/genética , RNA Circular/genética , Proteína Smad4/genética , Neoplasias Gástricas/genética , beta Catenina/genética , Carcinogênese/genética , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Neoplasias Gástricas/patologia , Via de Sinalização Wnt/genética
16.
Korean J Parasitol ; 58(5): 583-587, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33202512

RESUMO

Blastocystis sp. is a kind of protozoa living in the intestinal tract of human and animals, which will cause intestinal diseases such as diarrhea, abdominal distension and vomiting. This paper was aimed to understand the infection of Blastocystis sp. In golden monkeys and the transmission path in North China. Thirty-seven feces samples from golden monkeys and 116 cockroach samples from Shijiazhuang Zoo were collected from July to October 2019 for PCR analysis of Blastocystis sp. Genetic diversity analysis was further conducted on the samples with positive PCR results. The results showed that the infection rate was 48.7% (18/37) in golden monkeys and 82.8% (96/116) in cockroaches, respectively. The genetic evolution analysis based on small subunit ribosomal RNA demonstrated that three subtypes (ST) of Blastocystis sp. including ST1, ST2, and ST3 existed in the intestinal tract of golden monkeys, while only ST2 was detected in the intestinal tract of cockroaches. This paper may provide supports for the quarantine and control of Blastocystis sp. for the zoo in Northern China.


Assuntos
Animais de Zoológico , Infecções por Blastocystis/transmissão , Infecções por Blastocystis/veterinária , Blastocystis/isolamento & purificação , Baratas/parasitologia , Vetores de Doenças , Insetos Vetores , Doenças dos Macacos/parasitologia , Doenças dos Macacos/transmissão , Doenças Parasitárias em Animais/parasitologia , Doenças Parasitárias em Animais/transmissão , Animais , Blastocystis/classificação , Blastocystis/genética , Infecções por Blastocystis/epidemiologia , Infecções por Blastocystis/parasitologia , Cercopithecus , China/epidemiologia , Fezes/parasitologia , Feminino , Masculino , Doenças dos Macacos/epidemiologia , Doenças Parasitárias em Animais/epidemiologia , Reação em Cadeia da Polimerase
17.
Parasitol Res ; 2020 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-33164154

RESUMO

The intracellular parasite Neospora caninum can parasitize all nucleated cells of the host. Dense granule proteins (GRAs) secreted by dense granules are an important material involved in the formation of parasitophorous vacuoles (PVs), which facilitate parasite survival and replication in host cells. Due to the secretory and immune properties of NcGRA7, it is considered to be a promising serodiagnosis marker and an effective neosporosis vaccine candidate. However, the intracellular regulatory mechanisms involved in NcGRA7-induced host responses have rarely been examined. Here, we used the CRISPR/Cas9 genome editing system to obtain a NcGRA7 knockout strain (ΔNcGRA7) and a NcGRA7 complementary strain (iΔNcGRA7) to study their function. We found that ΔNcGRA7 exhibited slower growth in vitro and weakened virulence in mice compared with Nc1 and iΔNcGRA7. All parasite strains can stimulate host immune cells to produce IFN-γ, and the amount of IFN-γ production stimulated by Nc1 was significantly higher than that stimulated by ΔNcGRA7. The transcription levels of the cellular immune factors GBP1, GBP2, IRGa6, and IRGb6 were significantly higher after stimulation with ΔNcGRA7 parasites than after stimulation with Nc1. Furthermore, ΔNcGRA7 infection resulted in greater IRGa6 recruitment to the PVM than Nc1 infection. ΔNcGRA7 parasites were more easily cleared by macrophages than Nc1 parasites. Collectively, these results showed that NcGRA7 plays an important role in regulating the immune factors of mice and the aggregation of IRGa6 at the PVM, which affects the pathogenicity of N. caninum.

18.
Int J Biol Macromol ; 2020 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-33166556

RESUMO

As a heparin analogue, sulfonated chitosan (SCS) has been confirmed to have similar structure and properties to heparin which is shown to be a linker molecule having specific binding sites with collagen fibrils. In this study, the effects of a varying concentration of SCS on the self-assembly process of type I collagen were investigated. The study on intermolecular interaction between collagen and SCS was carried out via using ultraviolet-visible (UV-vis) spectrophotometry and circular dichroism (CD) spectroscopy. The addition of SCS did not disrupt the triple helix conformation of collagen. However, the decreased value of Rpn showed that the SCS, to some extent, influenced the percentage of triple helix conformation. The turbidity measurements revealed that the self-assembly rate was increased in the presence of a low concentration of SCS whereas decreased with further increasing the SCS concentration. The observation of microstructure via scanning electron microscopy (SEM) and atomic force microscopy (AFM) exhibited the characteristic D-periodicity, indicating that the presence of SCS did not disrupt the self-assembly nature of collagen. Moreover, the addition of SCS facilitated the lateral aggregation of fibrils, leading to the formation of larger fibrils. The rheological analysis showed that the gelation time of collagen was prolonged with increasing the concentration of SCS, in support of a longer lag-phase duration detected in turbidimetric measurements. We expect that valuable data would be provided in this study for further developing of ECM analogues, and propitious performances could be endowed to these biomimetic materials after SCS incorporation.

19.
Front Genet ; 11: 562971, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33173536

RESUMO

Autism spectrum disorder (ASD) is a class of neurodevelopmental disorders characterized by genetic and environmental risk factors. The pathogenesis of ASD has a strong genetic basis, consisting of rare de novo or inherited variants among a variety of multiple molecules. Previous studies have shown that microRNAs (miRNAs) are involved in neurogenesis and brain development and are closely associated with the pathogenesis of ASD. However, the regulatory mechanisms of miRNAs in ASD are largely unclear. In this work, we present a stepwise method, ASDmiR, for the identification of underlying pathogenic genes, networks, and modules associated with ASD. First, we conduct a comparison study on 12 miRNA target prediction methods by using the matched miRNA, lncRNA, and mRNA expression data in ASD. In terms of the number of experimentally confirmed miRNA-target interactions predicted by each method, we choose the best method for identifying miRNA-target regulatory network. Based on the miRNA-target interaction network identified by the best method, we further infer miRNA-target regulatory bicliques or modules. In addition, by integrating high-confidence miRNA-target interactions and gene expression data, we identify three types of networks, including lncRNA-lncRNA, lncRNA-mRNA, and mRNA-mRNA related miRNA sponge interaction networks. To reveal the community of miRNA sponges, we further infer miRNA sponge modules from the identified miRNA sponge interaction network. Functional analysis results show that the identified hub genes, as well as miRNA-associated networks and modules, are closely linked with ASD. ASDmiR is freely available at https://github.com/chenchenxiong/ASDmiR.

20.
J Gene Med ; : e3296, 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33179372

RESUMO

BACKGROUND: Osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs) is crucial for the bone formation, and its dysfunction is reported to be linked to osteoporosis (OP). This study aims at probing into the function of lncRNA small nucleolar RNA host gene 16 (SNHG16) in modulating osteogenic differentiation of hBMSCs. METHODS: SNHG16 expression in hBMSCs obtained from OP patients was measured by quantitative real-time polymerase chain reaction (qRT-PCR). Gain-of-function and loss-of-function models of SNHG16 were established with hBMSCs. The expressions of OP-related genes (ALP, OCN, and OPN) in hBMSCs were deterrmined by qRT-PCR and Western blot. StarBase database, TargetScan7.2, miRDB and PicTar database were used to predict the binding sites between SNHG16 and miR-485-5p, miR-485-5p and 3'UTR of bone morphogenetic protein 7 (BMP7), respectively. Dual-luciferase reporter assay was used to determine the regulatory relationships between SNHG16 and miR-485-5p, miR-485-5p and 3'UTR of BMP7, respectively. RESULTS: SNHG16 was remarkably down-regulated in hBMSCs obtained from patients with OP. Overexpression of SNHG16 promoted osteogenic differentiation of hBMSCs, while knockdown of SNHG16 suppressed it. Mechanistically, miR-485-5p is a target of SNHG16, and miR-485-5p can reverse the function of SNHG16. BMP7 is also identified as a target of miR-485-5p and can be indirectly modulated by SNHG16 in hBMSCs. CONCLUSION: SNHG16 promotes osteogenic differentiation of hBMSCs via regulating miR-485-5p/BMP7 axis, and can be a prospective therapy target for OP.

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