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1.
Sci Total Environ ; 807(Pt 2): 150833, 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34627908

RESUMO

Short-chain chlorinated paraffins (SCCPs) are persistent organic pollutants that are present in relatively high concentrations in various environmental media in China. Many studies have focused on chlorinated paraffins in soil from agricultural land and contaminated areas. There are limited data on the levels of chlorinated paraffins in soil from urban areas. In this study, to investigate the levels, distribution, and homolog patterns of chlorinated paraffins (CPs) in soil from a typical urban area, 130 soil samples were collected and combined to form 26 pooled samples. The samples were analyzed for 50 CP congener groups (C9-17Cl5-10). The concentration ranges for SCCPs, medium-chain CPs (MCCP), and chlorinated nonane paraffin (C9-CP) were 19-1456 ng/g (average: 234 ng/g), <10-385 ng/g (average: 54 ng/g), and 1-39 ng/g (average: 11 ng/g), respectively. The CP concentrations were not significantly correlated with the total organic carbon content (P > 0.05). Compared with other areas worldwide, the SCCP and C9-CP concentrations in soil in this area were at the medium level, and the concentrations of MCCPs were at a low level. The CP concentrations were higher in soil samples collected near factories and domestic garbage disposal sites. C10Cl6-7 were the main SCCP homologs and C14Cl7-8 were the main MCCP homologs. Principal component analysis showed that the sources of C9-CPs, SCCPs, and MCCPs in the soils were similar. Risk assessment showed that the concentrations of SCCPs and MCCPs in soil in this area did not pose a significant risk to soil organisms or human health.

2.
Biomed Eng Online ; 20(1): 96, 2021 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-34600551

RESUMO

BACKGROUND: Because of osteoporosis, traffic accidents, falling from high places, and other reasons, the vertebral body can be compressed and even collapse. Vertebral implants can be used for clinical treatment. Because of the advantages of honeycomb sandwich structures, such as low cost, less material, light weight, high strength, and good cushioning performance. In this paper, the honeycomb sandwich structure was used as the basic structure of vertebral implants. METHODS: The orthogonal experiment method is applied to analyse the size effect of honeycomb sandwich structures by the finite element method. Based on the minimum requirements of three indexes of peak stress, axial deformation, and anterior-posterior deformation, the optimal structure size was determined. Furthermore, through local optimization of the overall structure of the implant, a better honeycomb sandwich structure vertebral implant was designed. RESULTS: The optimal structure size combination was determined as a panel thickness of 1 mm, wall thickness if 0.49 mm, cell side length of 1 mm, and height of 6 mm. Through local optimization, the peak stress was further reduced, the overall stress distribution was uniform, and the deformation was reduced. The optimized peak stress decreased to 1.041 MPa, the axial deformation was 0.1110%, and the anterior-posterior deformation was 0.0145%. A vertebral implant with good mechanical performance was designed. CONCLUSIONS: This paper is the first to investigate vertebral implants with honeycomb sandwich structures. The design and analysis of the vertebral implant with a honeycomb sandwich structure were processed by the finite element method. This research can provide a feasible way to analyse and design clinical implants based on biomechanical principles.

3.
Ann Palliat Med ; 10(9): 9594-9606, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34628885

RESUMO

BACKGROUND: ICU-acquired weakness (ICU-AW) is characterized by neuromuscular damage such as limb weakness, yet the cause of ICU-AW remains unclear, which significantly increases the time a patient spends on mechanical ventilation (MV)/in ICU and can even affect a patient's survival rate and quality of life after being discharged. Pulmonary rehabilitation (PR)-related measures can effectively improve the ICU-AW situation, but in the specific implementation actions, many obstacles have been produced, and the treatment effect has been controversial, especially in the application process of mechanically ventilated patients. This study aims to confirm the efficacy of using MV alongside PR for patients with ICU-AW. METHODS: We obtained related randomized controlled trials (RCTs) from Chinese and English databases. All RCTs relevant to the use of PR in ICU-AW patients were retrieved from the following databases from their date of inception through January 31th, 2021: PubMed, EMBASE, The Cochrane Central Register of Controlled Trials, CINAHL, Joanna Briggs Institute (JBI), Web of Science, The Wanfang Database, and CNKI. This literature underwent screening, quality evaluation, and index data extraction by two independent researchers. The evaluation data were meta-analyzed with RevMan 5.3 software (Cochrane, London, UK). RESULTS: In total, we analyzed 15 articles which included 1,710 patients. We found that using PR alongside MV can effectively improve a patient's Medical Research Council (MRC) muscle strength score [mean difference (MD) =4.92, P=0.07], reduce the prevalence of ICU-AW [odds ratio (OR) =0.24, P<0.001], and shorten both MV duration [standardized mean difference (SMD) =-1.50, P<0.001] and ICU stay (SMD =-0.68, P=0.03). DISCUSSION: Implementing PR alongside MV can effectively reduce ICU-AW in patients. However, our standardized cluster PR study still requires further clarification to confirm how various intervention methods can reduce ICU-AW.


Assuntos
Unidades de Terapia Intensiva , Respiração Artificial , Humanos , Londres , Debilidade Muscular , Prevalência
4.
BMC Plant Biol ; 21(1): 457, 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34620078

RESUMO

BACKGROUND: Inoculation of arbuscular mycorrhizal (AM) fungi has the potential to alleviate salt stress in host plants through the mitigation of ionic imbalance. However, inoculation effects vary, and the underlying mechanisms remain unclear. Two maize genotypes (JD52, salt-tolerant with large root system, and FSY1, salt-sensitive with small root system) inoculated with or without AM fungus Funneliformis mosseae were grown in pots containing soil amended with 0 or 100 mM NaCl (incrementally added 32 days after sowing, DAS) in a greenhouse. Plants were assessed 59 DAS for plant growth, tissue Na+ and K+ contents, the expression of plant transporter genes responsible for Na+ and/or K+ uptake, translocation or compartmentation, and chloroplast ultrastructure alterations. RESULTS: Under 100 mM NaCl, AM plants of both genotypes grew better with denser root systems than non-AM plants. Relative to non-AM plants, the accumulation of Na+ and K+ was decreased in AM plant shoots but increased in AM roots with a decrease in the shoot: root Na+ ratio particularly in FSY1, accompanied by differential regulation of ion transporter genes (i.e., ZmSOS1, ZmHKT1, and ZmNHX). This induced a relatively higher Na+ efflux (recirculating) rate than K+ in AM shoots while the converse outcoming (higher Na+ influx rate than K+) in AM roots. The higher K+: Na+ ratio in AM shoots contributed to the maintenance of structural and functional integrity of chloroplasts in mesophyll cells. CONCLUSION: AM symbiosis improved maize salt tolerance by accelerating Na+ shoot-to-root translocation rate and mediating Na+/K+ distribution between shoots and roots.

5.
Artigo em Inglês | MEDLINE | ID: mdl-34486792

RESUMO

In this study, a bioactive composite material based on calcium sulfate hemihydrate (CSH) bone cement was studied, which use calcium sulfate dihydrate (CSD) as coagulant and silk fibroin nanofibers (SFF) solution as the curing liquid, further loaded vancomycin silk fibroin microspheres (SFM/VCM). The drug release effect of bone cements caused by tuning weight content of SFM/VCM (0.5, 1, 2%) and the concentration of silk fibroin solution (SFS) (20, 60, 100 mg/mL) used for preparation of SFM was studied in this article. Scanning electron microscope (SEM) demonstrated that the average diameter of microspheres gradually increased and the setting time was prolonged with the concentration of SFS increasing. X-ray diffraction (XRD) and Fourier transform infrared (FTIR) were used to analyze the composition of composite materials. The result of compressive strength revealed that the composites contained 0.5% SFM/VCM showed better mechanical performance independent on the concentration of microspheres and the cumulative drug release percentage of all composites were less than 55% after 4 weeks. The drug-loading bone cement possesses not only injectability but also sustained release capability which has a promising prospect in the field of bone substitute material.

6.
mSystems ; : e0080721, 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34491088

RESUMO

Nitrogen in different chemical forms is critical for metabolic alterations in Monascus strains and associated pigment diversity. In this study, we observed that ammonium-form nitrogen was superior in promoting the biosynthesis of Monascus pigments (MPs) when compared with nitrate and organic forms. Moreover, with any nitrogen source, the production of yellow and orange pigments was highly synchronized but distantly related to red pigments. However, transcriptional analyses of MP gene clusters suggested a low contribution to MP accumulation, suggesting that MP-limiting factors were located outside the gene cluster. Our metabolomic analyses demonstrated that red pigment biosynthesis was closely related to intracellular amino acids, whereas orange and yellow pigments were associated with nucleotides. In addition, weighted gene coexpression network analyses (WGCNA) based on transcriptomic data showed that multiple primary metabolic pathways were closely related to red pigment production, while several secondary pathways were related to orange pigments, and others were involved with yellow pigment regulation. These findings demonstrate that pigment diversity in Monascus is under combined regulation at metabolomic and transcriptomic levels. IMPORTANCE Natural MPs containing a mixture of red, orange, and yellow pigments are widely used as food coloring agents. MP diversity provides foods with versatile colors and health benefits but, in turn, complicate efforts to achieve maximum yield or desirable combination of pigments during the manufacturing process. Apart from the MP biosynthetic gene cluster, interactions between the main biosynthetic pathways and other intracellular genes/metabolites are critical to our understanding of MP differentiation. The integrative multiomics analytical strategy provides a technical platform and new perspectives for the identification of metabolic shunting mechanisms in MP biosynthesis. Equally, our research highlights the influence of intracellular metabolic alterations on MP differentiation, which will facilitate the rational engineering and optimization of MP production in the future.

7.
Eur J Pharmacol ; 910: 174470, 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34478691

RESUMO

Myocardial fibrosis in post-myocardial infarction is a self-healing process of the myocardium, making ventricular remodelling difficult to reverse and develop continuously. Fibroblast growth factor 21 (FGF21) plays an essential role in cardiovascular and metabolic diseases. However, the effect and mechanism of FGF21 action on cardiac inflammation and fibrosis caused by myocardial injury have rarely been reported. Adult male Sprague-Dawley rats administered with or without recombinant human basic FGF21 (rhbFGF21) were assessed using echocardiography and haematoxylin-eosin and Masson's trichrome staining to determine the cardiac function and cardiac inflammation and fibrosis levels. FGF21 might improve cardiac remodelling, as characterised by a decrease in the expression of a series of inflammatory and fibrosis-related factors. Moreover, when FGF receptors (FGFRs) were blocked, the effects of FGF21 disappeared. Mechanistically, we found that oxidative stress induced the downregulation of early growth response protein 1 (EGR1), which contributed to inflammatory factors and fibrosis reduction in cardiomyocytes treated with H2O2. Collectively, FGF21 effectively suppressed the inflammation and fibrosis in post-infarcted hearts by regulating FGFR-EGR1.

8.
Int J Mol Sci ; 22(18)2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34576166

RESUMO

Salmonella enterica serovar Typhi (S. Typhi) is a human-limited intracellular pathogen and the cause of typhoid fever, a severe systemic disease. Pathogen-host interaction at the metabolic level affects the pathogenicity of intracellular pathogens, but it remains unclear how S. Typhi infection influences host metabolism for its own benefit. Herein, using metabolomics and transcriptomics analyses, combined with in vitro and in vivo infection assays, we investigated metabolic responses in human macrophages during S. Typhi infection, and the impact of these responses on S. Typhi intracellular replication and systemic pathogenicity. We observed increased glucose content, higher rates of glucose uptake and glycolysis, and decreased oxidative phosphorylation in S. Typhi-infected human primary macrophages. Replication in human macrophages and the bacterial burden in systemic organs of humanized mice were reduced by either the inhibition of host glucose uptake or a mutation of the bacterial glucose uptake system, indicating that S. Typhi utilizes host-derived glucose to enhance intracellular replication and virulence. Thus, S. Typhi promotes its pathogenicity by inducing metabolic changes in host macrophages and utilizing the glucose that subsequently accumulates as a nutrient for intracellular replication. Our findings provide the first metabolic signature of S. Typhi-infected host cells and identifies a new strategy utilized by S. Typhi for intracellular replication.

9.
J Biomater Sci Polym Ed ; : 1-18, 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34517778

RESUMO

At present, the treatment of bone defect is one of the most concerned problems in biomedical fields. Despite the wide variety of scaffolds, there is a challenge to select materials that can mimic the structural integrity and biocompatibility of natural bone. In our study, gelatin methacryloyl (GelMA) and sodium alginate (Alg) were used to prepare three-dimensional (3D) GelMA/Alg hybrid hydrogel, which can simulate the structure and biological function of natural extracellular matrix due to their high water content and porous structure. The interconnected and homogeneous pores of the scaffold facilitate the transport of nutrients during the bone regeneration. Then hydroxyapatite (HA) coated GelMA/Alg (GelMA/Alg-HA) hydrogel was obtained by sequential mineralization. The mineralized hydrogel was obtained by immersing hydrogel alternately in a solution of calcium and phosphorus at 37 °C. The hydrogel was modified with a coating of HA under a mild condition. The calcium crosslinked Alg could provide nucleation sites for HA crystals. And the sequential mineralization will improve the physical properties and osteoinductivity of the hydrogels by introducing HA, which is similar to the mineral component of natural bone. Analytical results confirmed that the HA particles were uniformly distributed in the surface of the hydrogels and the mineral contents were about 40% after three cycles. The compressive strength was improved from 22.43 ± 6.39 to 131.03 ± 9.26 kPa. In addition, MC3T3-E1 cell co-culture experiments shown that the mineralized GelMA/Alg-HA hybrid hydrogel possess good biocompatibility, which is conducive to the growth of new bone tissue and bone repair.

10.
Colloids Surf B Biointerfaces ; 208: 112080, 2021 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-34481247

RESUMO

The paper describes the preparation of a porous bombyx mori silk fibroin (SF)/wool keratin (WK) composite scaffold with mimic structure and function for cartilage tissue engineering. A porous composite scaffold made from SF/WK in an appropriate concentration and mass ratio was prepared using a freeze-drying technique. Results showed that the composite scaffolds are water-insoluble; possess good mechanical properties, porosity above 80%, and pore size above 200 µm. Larger pore size and better connectivity of the composite scaffold than the pure SF scaffolds were contributed by the WK addition. The heat resistance and water-swelling of WK enhanced the thermal and mechanical properties of the composite scaffolds. In vitro cytotoxicity assessments showed cells with a good growth state, confirming no toxicity to the cells. The results of in vivo biocompatibility assessments exhibited that there is almost no inflammatory response in the implantation site tissue of the rats. The development of porous SF/WK composite scaffold has the potential in cartilage tissue engineering.

11.
Appl Microbiol Biotechnol ; 105(20): 7619-7634, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34559284

RESUMO

In this work, the application of chemical surfactants, including cooking aids, detergents, surface sizing agents, and deinking agents as core components, is introduced in the wet end of pulping and papermaking. This method for the combined application of enzymes and surfactants has expanded, promoting technological updates and improving the effect of surfactants in practical applications. Finally, the potential substitution of green surfactants for chemical surfactants is discussed. The source, classification, and natural functions of green surfactants are introduced, including plant extracts, biobased surfactants, fermentation products, and woody biomass. These green surfactants have advantages over their chemically synthesized counterparts, such as their low toxicity and biodegradability. This article reviews the latest developments in the application of surfactants in different paper industry processes and extends the methods of use. Additionally, the application potential of green surfactants in the field of papermaking is discussed. KEY POINTS: • Surfactants as important chemical additives in papermaking process are reviewed. • Deinking technologies by combined of surfactants and enzymes are reviewed. • Applications of green surfactant in papermaking industry are prospected.


Assuntos
Indústrias , Tensoativos , Biomassa , Fermentação
12.
Int J Food Microbiol ; 358: 109405, 2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34563883

RESUMO

Cronobacter spp. are foodborne pathogens that can cause severe infections in neonates through contaminated powdered infant formula. Accurate and rapid pathogen identification and serotyping are crucial to limit the detrimental effects of bacterial infections, and to prevent outbreaks and sporadic infections. Conventional serotyping is tedious, laborious, and time-consuming; however, with whole-genome sequencing (WGS) becoming faster and cheaper, WGS has vast potential in routine typing and surveillance. Hence, in this study, we developed a publicly available tool, CroTrait (CronobacterTraits), for in silico species identification and O serotyping of Cronobacter isolates based on WGS data. CroTrait showed excellent performance in species identification and O serotyping when 810 genomes with known species identities and 276 genomes with known O serotype were tested. Moreover, CroTrait allows rapid prediction of new potential O serotypes. We identified 11 novel potential O serotypes of Cronobacter using CroTrait. Therefore, CroTrait is a convenient and promising tool for species identification and O serotyping of Cronobacter isolates.

13.
Appl Microbiol Biotechnol ; 105(16-17): 6369-6379, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34402939

RESUMO

Monascus yellow pigments (MYPs), as food colorants, are of great interest to the food industry, because of their beneficial biological activities. In this study, a comparative metabolomics strategy revealed the metabolic regulatory mechanism of MYP overproduction, comparing ammonium chloride with peptone as nitrogen sources. Metabolomics-based multivariate regression modeling showed that metabolic biomarkers/modules, such as glucose, lactate, and the pentose phosphate (PP) pathway, were closely associated with the biosynthesis of MYPs. Exogenous addition of glucose increased production of MYPs, whereas lactate reduced it. Inhibition of the PP pathway with dehydroepiandrosterone decreased MYP production, while increasing the shunting production of orange and red pigments. All these treatments significantly changed the expression profiles of the pigment biosynthetic gene cluster and the mycelial morphology. Overall, this study demonstrates the feasibility of elucidating the mechanism of MYP biosynthesis by comprehensive metabolomics analysis, as well as discovering potential engineering targets of efficiency improvements to commercial MYP production. KEY POINTS: • Comparative metabolomics revealed the biomarkers/modules of MYP production. • A rational exogenously adding strategy was implemented to regulate MYP synthesis. • Expression profiles of gene cluster and mycelial morphology were characterized.


Assuntos
Monascus , Cloreto de Amônio , Metabolômica , Nitrogênio , Pigmentos Biológicos
14.
Artigo em Inglês | MEDLINE | ID: mdl-34464274

RESUMO

Differentiable ARchiTecture Search (DARTS) uses a continuous relaxation of network representation and dramatically accelerates Neural Architecture Search (NAS) by almost thousands of times in GPU-day. However, the searching process of DARTS is unstable, which suffers severe degradation when training epochs become large, thus limiting its application. In this article, we claim that this degradation issue is caused by the imbalanced norms between different nodes and the highly correlated outputs from various operations. We then propose an improved version of DARTS, namely iDARTS, to deal with the two problems. In the training phase, it introduces node normalization to maintain the norm balance. In the discretization phase, the continuous architecture is approximated based on the similarity between the outputs of the node and the decorrelated operations rather than the values of the architecture parameters. Extensive evaluation is conducted on CIFAR-10 and ImageNet, and the error rates of 2.25% and 24.7% are reported within 0.2 and 1.9 GPU-day for architecture search, respectively, which shows its effectiveness. Additional analysis also reveals that iDARTS has the advantage in robustness and generalization over other DARTS-based counterparts.

15.
Artigo em Inglês | MEDLINE | ID: mdl-34383214

RESUMO

Two novel absorbents were synthesized for the first time by banana and pomegranate peels using diethylenetriaminepentaacetic acid (DTPA) modification to eliminate Cd(II) and Ni(II) of sewage. The DTPA-modified peels performed significantly higher adsorption capacity than unmodified materials. The maximum adsorption capacities of DTPA-modified banana/pomegranate peel were 46.729/46.296 mg/g for Cd(II), and 29.240/16.611 mg/g for Ni(II). Adsorption isotherm and kinetics models were simulated to determine their removal efficiency and potential for recovery of these two heavy metals. As the results, the adsorption reached equilibrium within 5 min and was well described by the pseudo-second order model and Langmuir isotherm. The surface morphology analysis of the synthetic materials by Scanning Electron Microscopy-Energy Dispersive X-ray spectroscopy, Fourier Transform Infrared spectroscopy, and X-ray Photoelectron Spectroscopy, implied that ion exchange, complexation, and physical adsorption may together contribute to Cd(II) and Ni(II) loading on DTPA-modified peels. This study demonstrates the feasibility of waste peels as cost-efficient bio-absorbents to remove Cd(II) and Ni(II) in sewage systems, and discovers potential adsorption mechanism of efficiency improvements after DTPA modification.

16.
Bioelectrochemistry ; 142: 107928, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34428614

RESUMO

Prostate cancer is one of the most common cancers in the world, and its early detection is vital to saving the lives of patients. In this research, a novel label-free photoelectrochemical immunosensor was designed for sensitive detection of prostate specific antigen (PSA). Ag2S sensitized on Ag/AgBr/BiOBr heterojunction could effectively inhibit photogenic holes recombination and improve photocurrent response and sensitivity. Ascorbic acid was an effective electron donor, which can effectively eliminate photo-generated holes. The photocurrent reduced linearly with the logarithm of PSA concentration ranged from 0.001 to 50 ng·mL-1 and the limit of detection was 0.25 pg·mL-1. The designed sensor had the advantages of wide linear range, good stability, high reproducibility, and good selectivity. This study not only provided a method for efficient and sensitive detection of PSA, but also provided valuable reference ideas for the detection of other tumor markers.

17.
Ophthalmic Genet ; : 1-26, 2021 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-34455905

RESUMO

Background: Stargardt disease (STGD1) is an autosomal recessive retinal dystrophy due to mutations in ABCA4, characterized by subretinal deposition of lipofuscin-like substances and bilateral centrifugal vision loss. Despite the tremendous progress made in the understanding of STGD1, there are no approved treatments to date. This review examines the challenges in the development of an effective STGD1 therapy.Materials and Methods: A literature review was performed through to June 2021 summarizing the spectrum of retinal phenotypes in STGD1, the molecular biology of ABCA4 protein, the in vivo and in vitro models used to investigate the mechanisms of ABCA4 mutations and current clinical trials.Results: STGD1 phenotypic variability remains an challenge for clinical trial design and patient selection. Pre-clinical development of therapeutic options has been limited by the lack of animal models reflecting the diverse phenotypic spectrum of STDG1. Patient-derived cell lines have facilitated the characterization of splice mutations but the clinical presentation is not always predicted by the effect of specific mutations on retinoid metabolism in cellular models. Current therapies primarily aim to delay vision loss whilst strategies to restore vision are less well developed.Conclusions: STGD1 therapy development can be accelerated by a deeper understanding of genotype-phenotype correlations.

18.
Biomed Pharmacother ; 142: 111907, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34339916

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Huangqi Guizhi Wuwu Decoction(HQGZWWD) is a Traditional Chinese Medicine formula from Synopsis of Golden Chamber used to treat blood arthralgia. According to the principle that the same treatment can be used for different diseases, HQGZWWD has proven effective for IgA nephropathy (IgAN) associated with spleen and kidney yang deficiency. AIM OF THE STUDY: In this study, we investigated the mechanism by which HQGZWWD alleviates proteinuria and protects renal function in rats with IgAN by regulating the AT1R/Nephrin/c-Abl pathway. METHODS: Rats were randomly divided into six groups: control, IgAN model, IgAN model treated with low-dose HQGZWWD, IgAN model treated with medium-dose HQGZWWD, IgAN model treated with high-dose HQGZWWD, and IgAN model treated with valsartan. IgAN was induced using bovine γ-globulin. We evaluated the mediating effects of HQGZWWD on podocyte cytoskeletal proteins, the AT1R/Nephrin/c-Abl pathway, upstream tumor necrosis factor-α (TNF-α), and TNF-α receptor-1 (TNFR1). RESULTS: The IgAN rats displayed proteinuria, IgA deposition in the mesangial region, and podocyte cytoskeletal protein damage. The expression of TNF-α, TNFR1, AT1R, and c-Abl was increased in the IgAN rat kidney, whereas the expression of nephrin, podocin, ACTN4, and phosphorylated nephrin (p-nephrin) was reduced. HQGZWWD treatment significantly alleviated podocyte cytoskeletal protein damage in the IgAN rats, upregulated the expression of nephrin, podocin, and ACTN4, and the colocalized expression of F-actin and nephrin. This study demonstrates that HQGZWWD attenuates podocyte cytoskeletal protein damage by regulating the AT1R-nephrin- c-Abl pathway, upregulating the expression of p-nephrin, and downregulating the expression of AT1R and c-Abl. CONCLUSIONS: These results indicate that HQGZWWD attenuates podocyte cytoskeletal protein damage in IgAN rats by regulating the AT1R/Nephrin/c-Abl pathway, providing a potential therapeutic approach for IgAN.

19.
Stem Cell Res ; 54: 102448, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34198153

RESUMO

Stargardt disease (STGD1) is the most common inherited retinal dystrophy and ABCA4 c.546--10 T>C is the most commonly reported splice mutation. Here, we generated and characterized two induced pluripotent stem cell (iPSC) lines from a STGD1 patient with compound heterozygous mutations in ABCA4 (c.[5461-10 T > C;5603A > T];[4163 T > C;455G > A]). Episomal vectors containing OCT4, SOX2, KLF4, L-MYC, LIN28 and mp53DD were employed to conduct the reprogramming of patient-derived fibroblasts. Both lines had a normal karyotype, displayed iPSC morphology, expressed pluripotency markers and showed trilineage differentiation potential. These lines can provide a powerful platform for further investigating the pathophysiological consequences of mutations in ABCA4.


Assuntos
Células-Tronco Pluripotentes Induzidas , Transportadores de Cassetes de Ligação de ATP/genética , Diferenciação Celular , Linhagem Celular , Humanos , Mutação , Doença de Stargardt
20.
Stem Cell Res ; 54: 102439, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34214897

RESUMO

Mutations in ABCA4 gene are causative for autosomal recessive Stargardt disease (STGD1), the most common inherited retinal dystrophy. Here, we report the generation of an induced pluripotent stem cell (iPSC) line from a STGD1 patient carrying biallelic c.[5461-10T>C;5603A>T];[6077T>C] mutations in the ABCA4 gene. Episomes carrying OCT4, SOX2, KLF4, L-MYC, LIN28 and mp53DD were employed for the reprogramming of patient-derived fibroblasts. This iPSC line expressed comparable pluripotency markers as in a commercially available human iPSC line, displayed normal karyotype and potential for trilineage differentiation, and were negative for both reprogramming episomes and mycoplasma test.


Assuntos
Células-Tronco Pluripotentes Induzidas , Transportadores de Cassetes de Ligação de ATP/genética , Diferenciação Celular , Humanos , Mutação , Doença de Stargardt
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