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1.
Food Chem ; 449: 139187, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38604029

RESUMO

Pickering emulsions stabilized by protein particles are of great interest for use in real food systems. This study was to investigate the properties of microgel particles prepared from different plant proteins, i.e., soybean protein isolate (SPI), pea protein isolate (PPI), mung bean protein isolate (MPI), chia seed protein isolate (CSPI), and chickpea protein isolate (CPI). MPI protein particles had most desirable Pickering emulsion forming ability. The particles of SPI and PPI had similar particle size (316.23 nm and 294.80 nm) and surface hydrophobicity (2238.40 and 2001.13) and emulsion forming ability, while the CSPI and CPI particle stabilized emulsions had the least desirable properties. The MPI and PPI particle stabilized Pickering emulsions produced better quality ice cream than the one produced by SPI particle-stabilized emulsions. These findings provide insight into the properties of Pickering emulsions stabilized by different plant protein particles and help expand their application in emulsions and ice cream.


Assuntos
Emulsões , Tamanho da Partícula , Proteínas de Plantas , Emulsões/química , Proteínas de Plantas/química , Microgéis/química , Interações Hidrofóbicas e Hidrofílicas , Sorvetes/análise , Cicer/química , Vigna/química
2.
Leuk Lymphoma ; : 1-9, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38475670

RESUMO

Cytomegalovirus (CMV) reactivation increases treatment-related mortality (TRM) after allogeneic hematopoietic cell transplantation (allo-HCT). We analyzed 141 adult acute leukemia (AL) patients suffered allo-HCT between 2017 and 2021, who developed CMV viremia post-HCT and treated with valganciclovir or foscarnet, to evaluate effectiveness and safety of both drugs. Viremia clearance rates (14 and 21 d post treatment) and toxicities were similar in two groups. However, valganciclovir was associated with a lower cumulative incidence of CMV recurrence within 180 days (16.7% vs. 35.7%, p=0.029) post CMV clearance. Finally, 2-year TRM was lower in valganciclovir group (9.7% ± 0.2% vs. 26.2% ± 0.3%, p = 0.026), result a superior 2-year overall survival (OS; 88.1% ± 5.2% vs. 64.4% ± 5.5%, p = 0.005) and leukemia-free survival (LFS; 82.0% ± 5.9% vs. 58.9% ± 5.6%, p = 0.009). Valganciclovir might decrease CMV viremia recurrence and led to better long-term outcome than foscarnet in adult AL patients developed CMV viremia post-HCT. Considering the inherent biases of retrospective study, well-designed trials are warranted to validate our conclusion.

3.
Histopathology ; 84(6): 1024-1037, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38253913

RESUMO

AIMS: Histological chorioamnionitis (HCA) is a condition linked to preterm birth and neonatal infection and its relationship with various pathological stages in extremely preterm neonates, and with their associated short- and long-term consequences, remains a subject of research. This study investigated the connection between different pathological stages of HCA and both short-term complications and long-term outcomes in preterm infants born at or before 32 weeks of gestational age. METHODS: Preterm infants born at ≤ 32 weeks of gestation who underwent placental pathology evaluation and were followed-up at 18-24 months of corrected age were included. Neonates were classified based on their exposure to HCA and were further subdivided into different groups according to maternal inflammatory responses (MIR) and fetal inflammatory responses (FIR) stages. We compared short-term complications during their hospital stay between the HCA-exposed and -unexposed groups and examined the influence of HCA stages on long-term outcomes. RESULTS: The HCA group exhibited distinct characteristics such as higher rates of premature rupture of membranes > 18 h, reduced amniotic fluid, early-onset sepsis, bronchopulmonary dysplasia and intraventricular haemorrhage (IVH) grades III-IV (P < 0.05). The moderate-severe HCA group displayed lower gestational age, lower birth weight and higher incidence of IVH (grades III-IV) and preterm sepsis compared with the mild HCA group (P < 0.05). After adjusting for confounders, the MIR stages 2-3 group showed associations with cognitive impairment and cerebral palsy (P < 0.05), and the FIR stages 2-3 group also showed poor long-term outcomes and cognitive impairment (P < 0.05). CONCLUSIONS: Moderate-severe HCA was associated with increased early-onset sepsis, severe IVH and poor long-term outcomes, including cognitive impairment and cerebral palsy. Vigilant prevention strategies are warranted for severe HCA cases in order to mitigate poorer clinical outcomes.


Assuntos
Paralisia Cerebral , Corioamnionite , Ruptura Prematura de Membranas Fetais , Nascimento Prematuro , Sepse , Lactente , Recém-Nascido , Humanos , Feminino , Gravidez , Recém-Nascido Prematuro , Corioamnionite/epidemiologia , Corioamnionite/etiologia , Corioamnionite/patologia , Placenta/patologia , Ruptura Prematura de Membranas Fetais/patologia , Paralisia Cerebral/complicações , Paralisia Cerebral/patologia , Nascimento Prematuro/etiologia , Nascimento Prematuro/epidemiologia , Nascimento Prematuro/patologia , Fatores de Risco , Idade Gestacional , Sepse/complicações , Sepse/patologia
4.
Int J Biol Macromol ; 257(Pt 1): 128183, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37977455

RESUMO

Pickering emulsions are of great interest to the food industry and their freeze-thaw stability important when used in frozen foods. Particles of soybean isolate (SPI) were heat treated and then crosslinked with transglutaminase (TG) enzyme to produce Pickering emulsions. The protein particles produced using unheated and uncrosslinked SPI (NSPI) was used as the benchmark. The mean particle size, absolute zeta potential, and surface hydrophobicity of protein particles produced using heat treatment and TG crosslinking (at 40 U/g) SPI (HSPI-TG-40) were the highest and substantially higher than those produced using NSPI. The thermal treatment of protein particles followed by crosslinking with TG enzyme improved the freeze-thaw stability of Pickering emulsions stabilized by them. The Pickering emulsions produced using HSPI-TG-40 had the lowest temperature for ice crystal formation and they had better freeze-thaw stability. The plant-based ice cream prepared by HSPI-TG-40 particle-stabilized Pickering emulsions had suitable texture and freeze-thaw stability compared to the ice cream produced using NSPI. The Pickering particles produced using heat treatment of SPI followed by crosslinking with TG (at 40 U/g) produced the most freeze-thaw stable Pickering emulsions. These Pickering particles and Pickering emulsions could be used in frozen foods such as ice cream.


Assuntos
Sorvetes , Proteínas de Soja , Proteínas de Soja/química , Emulsões/química , Congelamento , Temperatura Baixa , Tamanho da Partícula
5.
Plant J ; 117(1): 107-120, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37753665

RESUMO

Black pepper (Piper nigrum L.), the world renown as the King of Spices, is not only a flavorsome spice but also a traditional herb. Piperine, a species-specific piper amide, is responsible for the major bioactivity and pungent flavor of black pepper. However, several key steps for the biosynthesis of piperoyl-CoA (acyl-donor) and piperidine (acyl-acceptor), two direct precursors for piperine, remain unknown. In this study, we used guilt-by-association analysis of the combined metabolome and transcriptome, to identify two feruloyldiketide-CoA synthases responsible for the production of the C5 side chain scaffold feruloyldiketide-CoA intermediate, which is considered the first and important step to branch metabolic fluxes from phenylpropanoid pathway to piperine biosynthesis. In addition, we also identified the first two key enzymes for piperidine biosynthesis derived from lysine in P. nigrum, namely a lysine decarboxylase and a copper amine oxidase. These enzymes catalyze the production of cadaverine and 1-piperideine, the precursors of piperidine. In vivo and in vitro experiments verified the catalytic capability of them. In conclusion, our findings revealed enigmatic key steps of piperine biosynthetic pathway and thus provide a powerful reference for dissecting the biosynthetic logic of other piper amides.


Assuntos
Piper nigrum , Piper nigrum/genética , Alcamidas Poli-Insaturadas , Piperidinas , Perfilação da Expressão Gênica , Metaboloma
6.
Int J Biol Macromol ; 258(Pt 1): 128770, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38104689

RESUMO

The blend films made of food soft matter are of growing interest to the food packaging industries as a pro-environment packaging option. The blend films have become a novel pattern to replace traditional plastics gradually due to their characteristics of biodegradability, sustainability, and environmental friendliness. This review discussed the whole process of the manufacturing of food soft matter blend films from the raw material to the application due to multi-scale structural analysis. There are 3 stages and 12 critical analysis points of the entire process. The raw material, molecular self-assembly, film-forming mechanism and performance test of blend films are investigated. In addition, 11 kinds of blend films with different functional properties by casting are also preliminarily described. The industrialization progress of blend films can be extended or facilitated by analysis of the 12 critical analysis points and classification of the food soft matter blend films which has a great potential in protecting environment by developing sustainable packaging solutions.


Assuntos
Embalagem de Alimentos , Alimentos Orgânicos , Plásticos
7.
Int J Mol Sci ; 24(19)2023 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-37833925

RESUMO

Pseudorabies virus (PRV), an alpha herpesvirus, induces significant economic losses to the swine industry and infects multiple kinds of animals. Therefore, it is of great importance to explore anti-PRV compounds. In this study, to explore the anti-PRV compounds, a library of natural compounds was screened through a cell-based ELISA assay, and it was discovered that bufalin, a Na+/K+-ATPase inhibitor, had a robust inhibitory effect on PRV replication. A time-of-addition experiment and temperature-shift assay showed that bufalin significantly inhibited the entry stage of PRV. NaCl- or KCl-treatment showed that NaCl could enhance the inhibitory effect of bufalin on PRV replication, whereas there was no significant effect under the treatment of KCl. Meanwhile, it was also found that bufalin possessed antiviral activity against other alpha herpesviruses, including human herpes simplex virus type 1 (HSV-1) and chicken Marek's disease virus (MDV). Finally, it was found that bufalin could decrease the viral load in multiple tissues, and reduce the morbidity and mortality in PRV-challenged BALB/c mice. Overall, our findings demonstrated that bufalin has the potential to be developed as an anti-PRV compound.


Assuntos
Herpesviridae , Herpesvirus Suídeo 1 , Camundongos , Animais , Suínos , Humanos , Cloreto de Sódio/farmacologia , Adenosina Trifosfatases
8.
Foods ; 12(19)2023 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-37835362

RESUMO

Walnut protein is a high-quality vegetable protein with promising applications in the food industry; however, its potential is hindered by low solubility and associated properties. We utilized various physical modification techniques (cold plasma; ball milling; superfine grinding; ultrasound; wet ball milling; and high-pressure microjet) to enhance walnut proteins' physicochemical and functional properties. The changes in particle size, microstructure, surface hydrophobicity, fluorescence, solubility, foaming, and emulsification were investigated. Cold plasma and ultrasound treatments minimally affected particle size and morphology. Cold plasma increased the particle size D4,3 from 145.20 µm to 152.50 µm. Ultrasonication reduced the particle size D4,3 to 138.00 µm. The variation was within ±10 µm, while the particle size of walnut protein significantly decreased after the other four modification treatments. The greatest variation in particle size was in the superfine grinding, with the D4,3 being reduced to 23.80 µm. Ultrasound treatment converted the ß-sheet into an α-helix, while the other methods transformed the α-helix into a ß-sheet. The dispersion stability notably improved after wet ball milling and high-pressure microjet treatments, which was accompanied by a significant increase in solubility from 6.9% (control) to 13.6% (wet ball milling) and 31.7% (high-pressure microjet). The foaming and emulsification properties were also enhanced through these modifications (foaming improved from 47% to 55.33% and emulsification improved from 4.32 m2/g to 8.27 m2/g). High-pressure microjet treatment proved most effective at improving solubility in the functional properties of walnut protein. These findings are expected to help broaden the potential utilization of walnut protein in the food industry, including in beverages and emulsions.

9.
Tissue Eng Part C Methods ; 29(11): 535-544, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37578128

RESUMO

The management of large amounts of bio-wastes, such as bovine femurs from kitchens and slaughterhouses, has long been a challenging issue. However, through the utilization of a hydrothermal process, it is possible to transform these bio-wastes into valuable products. In this study, we focused on extracting hydroxyapatite (HAp), the primary inorganic component of bovine femurs, for potential use in bone tissue engineering scaffolds. By subjecting the femurs to hydrothermal treatment at varying times and solvents, we successfully decomposed and removed the organic matter present, resulting in the extraction of HAp. To comprehensively evaluate the properties of the extracted HAp, we employed several characterization techniques that provided valuable insights into the structure, morphology, and elemental composition of the extracted HAp. Furthermore, we conducted a Cell Counting Kit-8 assay, which confirmed the favorable biocompatibility of the extracted HAp. Overall, this study highlights the potential of hydrothermal treatment as an environmentally friendly and cost-effective method for handling bio-waste, specifically bovine femurs. The extracted HAp exhibits promising characteristics, making it suitable for a wide range of biomedical applications. This research contributes to the sustainable utilization of bio-waste and underscores the importance of resourceful exploitation for environmental protection.


Assuntos
Durapatita , Alicerces Teciduais , Animais , Bovinos , Durapatita/química , Alicerces Teciduais/química , Engenharia Tecidual , Fêmur
10.
Nat Commun ; 14(1): 5242, 2023 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-37640697

RESUMO

Osteoarthritis is a prevalent age-related disease characterized by dysregulation of extracellular matrix metabolism, lipid metabolism, and upregulation of senescence-associated secretory phenotypes. Herein, we clarify that CircRREB1 is highly expressed in secondary generation chondrocytes and its deficiency can alleviate FASN related senescent phenotypes and osteoarthritis progression. CircRREB1 impedes proteasome-mediated degradation of FASN by inhibiting acetylation-mediated ubiquitination. Meanwhile, CircRREB1 induces RanBP2-mediated SUMOylation of FASN and enhances its protein stability. CircRREB1-FASN axis inhibits FGF18 and FGFR3 mediated PI3K-AKT signal transduction, then increased p21 expression. Intra-articular injection of adenovirus-CircRreb1 reverses the protective effects in CircRreb1 deficiency mice. Further therapeutic interventions could have beneficial effects in identifying CircRREB1 as a potential prognostic and therapeutic target for age-related OA.


Assuntos
Metabolismo dos Lipídeos , Osteoartrite , Animais , Camundongos , Condrócitos , Fosfatidilinositol 3-Quinases/genética , Processamento de Proteína Pós-Traducional , Fenótipo
12.
J Environ Manage ; 342: 118143, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37196621

RESUMO

The performance of an electric-integrated vertical flow constructed wetland (E-VFCW) for chloramphenicol (CAP) removal, changes in microbial community structure, and the fate of antibiotic resistance genes (ARGs) were evaluated. CAP removal in the E-VFCW system was 92.73% ± 0.78% (planted) and 90.80% ± 0.61% (unplanted), both were higher than the control system which was 68.17% ± 1.27%. The contribution of anaerobic cathodic chambers in CAP removal was higher than the aerobic anodic chambers. Plant physiochemical indicators in the reactor revealed electrical stimulation increased oxidase activity. Electrical stimulation enhanced the enrichment of ARGs in the electrode layer of the E-VFCW system (except floR). Plant ARGs and intI1 levels were higher in the E-VFCW than in the control system, suggesting electrical stimulation induces plants to absorb ARGs, reducing ARGs in the wetland. The distribution of intI1 and sul1 genes in plants suggests that horizontal transfer may be the main mechanism dispersing ARGs in plants. High throughput sequencing analysis revealed electrical stimulation selectively enriched CAP degrading functional bacteria (Geobacter and Trichlorobacter). Quantitative correlation analysis between bacterial communities and ARGs confirmed the abundance of ARGs relates to the distribution of potential hosts and mobile genetic elements (intI1). E-VFCW is effective in treating antibiotic wastewater, however ARGs potentially accumulate.


Assuntos
Cloranfenicol , Áreas Alagadas , Cloranfenicol/farmacologia , Cloranfenicol/análise , Genes Bacterianos , Antibacterianos/farmacologia , Antibacterianos/análise , Águas Residuárias , Bactérias/genética
13.
Regen Biomater ; 10: rbad040, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37250976

RESUMO

Polymethylmethacrylate (PMMA) bone cement extensively utilized for the treatment of osteoporotic vertebral compression fractures due to its exceptional handleability and mechanical properties. Nevertheless, the clinical application of PMMA bone cement is restricted by its poor bioactivity and excessively high modulus of elasticity. Herein, mineralized small intestinal submucosa (mSIS) was incorporated into PMMA to prepare a partially degradable bone cement (mSIS-PMMA) that provided suitable compressive strength and reduced elastic modulus compared to pure PMMA. The ability of mSIS-PMMA bone cement to promote the attachment, proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells was shown through cellular experiments carried out in vitro, and an animal osteoporosis model validated its potential to improve osseointegration. Considering these benefits, mSIS-PMMA bone cement shows promising potential as an injectable biomaterial for orthopedic procedures that require bone augmentation.

15.
Vet Sci ; 10(3)2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36977228

RESUMO

The pseudorabies virus is a widespread swine pathogen that has caused significant economic losses to the global pig industry. Due to the emergence of PRV variant strains in recent years, vaccines cannot provide complete protection against the infection of PRV. Therefore, the research on antiviral compounds is of great importance for PRV treatment. In this study, an EGFP-labeled PRV was used to screen anti-PRV compounds from 86 natural product extracts. Gallocatechin gallate was found to efficiently inhibit the replication of PRV with a half-maximal inhibitory concentration (IC50) of 0.41 µM. In addition, it was found that gallocatechin gallate was unable to directly inactivate PRV and had no effect on the attachment stage of PRV. However, it was found that gallocatechin gallate significantly suppressed the viral entry stage. Furthermore, it was found that the release stage of PRV was also significantly suppressed by gallocatechin gallate. Together, this study found that gallocatechin gallate could efficiently inhibit the replication of PRV by suppressing the entry and release stages of PRV, which will contribute to the development of a new therapeutic strategy against PRV infection.

16.
Aging (Albany NY) ; 15(5): 1564-1590, 2023 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-36897170

RESUMO

Circular RNAs (circRNAs) have been demonstrated to have critical regulatory roles in tumorigenesis. However, the contribution of circRNAs to OS (osteosarcoma) remains largely unknown. circRNA deep sequencing was performed to the expression of circRNAs between OS and chondroma tissues. The regulatory and functional role of circRBMS3 (a circRNA derived from exons 7 to 10 of the RBMS3 gene, hsa_circ_0064644) upregulation was examined in OS and was validated in vitro and in vivo, upstream regulator and downstream target of circRBMS3 were both explored. RNA pull down, a luciferase reporter assay, biotin-coupled microRNA capture and fluorescence in situ hybridization were used to evaluate the interaction between circRBMS3 and micro (mi)-R-424-5p. For in vivo tumorigenesis experiments, Subcutaneous and Orthotopic xenograft OS mouse models were built. Expression of circRBMS3 was higher in OS tissues due to the regulation of adenosine deaminase 1-acting on RNA (ADAR1), an abundant RNA editing enzyme. Our in vitro data indicated that ShcircRBMS3 inhibits the proliferation and migration of osteosarcoma cells. Mechanistically, we showed that circRBMS3 could regulate eIF4B and YRDC, through 'sponging' miR-424-5p. Furthermore, knockdown of circRBMS3 inhibited malignant phenotypes and bone destruction of OS in vivo. Our results reveal an important role for a novel circRBMS3 in the growth and metastasis of malignant tumor cells and offer a fresh perspective on circRNAs in OS progression.


Assuntos
Neoplasias Ósseas , MicroRNAs , Osteossarcoma , Humanos , Animais , Camundongos , RNA Circular/genética , RNA Circular/metabolismo , Hibridização in Situ Fluorescente , Linhagem Celular Tumoral , MicroRNAs/genética , MicroRNAs/metabolismo , Osteossarcoma/patologia , Neoplasias Ósseas/genética , Neoplasias Ósseas/patologia , Carcinogênese/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Proteínas de Ligação a RNA/genética , Proteínas de Ligação ao GTP/genética
17.
Commun Biol ; 6(1): 200, 2023 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-36806251

RESUMO

Osteoarthritis (OA) is a common chronic degenerative joint disease associated with a variety of risk factors including aging, genetics, obesity, and mechanical disturbance. This study aimed to elucidate the function of a newly discovered circular RNA (circRNA), circFNDC3B, in OA progression and its relationship with the NF-κB signaling pathway and oxidative stress. The circFNDC3B/miR-525-5p/HO-1 axis and its relationship with the NF-κB signaling pathway and oxidative stress were investigated and validated using fluorescence in situ hybridization, real-time PCR, western blotting, immunofluorescence analysis, luciferase reporter assays, pull-down assays, and reactive oxygen species analyses. The functions of circFNDC3B in OA was investigated in vitro and in vivo. These evaluations demonstrated that circFNDC3B promotes chondrocyte proliferation and protects the extracellular matrix (ECM) from degradation. We also revealed that circFNDC3B defends against oxidative stress in OA by regulating the circFNDC3B/miR-525-5p/HO-1 axis and the NF-κB signaling pathway. Further, we found that overexpression of circFNDC3B alleviated OA in a rabbit model. In summary, we identified a new circFNDC3B/miR-525-5p/HO-1 signaling pathway that may act to relieve OA by alleviating oxidative stress and regulating the NF-κB pathway, resulting in the protection of the ECM in human chondrocytes, highlighting it as a potential therapeutic target for the treatment of OA.


Assuntos
MicroRNAs , Osteoartrite , Humanos , Animais , Coelhos , NF-kappa B/genética , Hibridização in Situ Fluorescente , Estresse Oxidativo , Osteoartrite/genética , MicroRNAs/genética
18.
Clin Transl Med ; 13(1): e1158, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36604982

RESUMO

BACKGROUND: Circular RNAs (CircRNAs) are important and have different roles in disease progression. Herein, we aim to elucidate the roles of a novel CircRNA (CircZSWIM6) which is upregulated in ageing chondrocytes. METHODS: We verified the roles of CircZSWIM6 in senescent and osteoarthritis (OA) development in vitro through CircZSWIM6 knockdown and overexpression. RNA pulldown assay and RNA binding protein immunoprecipitation were performed to identify the interaction between CircZSWIM6 and Ribosomal protein S14 (RPS14). The roles of CircZSWIM6 in ageing-related OA were also confirmed in non-traumatic and traumatic model respectively. RESULTS: CircZSWIM6 regulates extracellular matrix (ECM) and energy metabolism in ageing chondrocyte. Mechanistically, CircZSWIM6 competitively bound to the E3 ligase STUB1 binding site on RPS14 (K125) to inhibit proteasomal degradation of RPS14 to maintain RPS14 function. CircZSWIM6-RPS14 axis is highly associated with AMPK signaling transduction, which keeps energy metabolism in chondrocyte. Furthermore, CircZSWIM6 AAV infection leads to senescent and OA phenotypes in a non-traumatic model and accelerates OA progression in a traumatic model. CONCLUSION: Our results revealed a significant role of CircZSWIM6 in age-related OA by regulating ECM metabolism and AMPK-associated energy metabolism. We highlight the CircZSWIM6-RPS14-PCK1-AMPK axis is a potential biomarker for OA.


Assuntos
Cartilagem Articular , MicroRNAs , Condrócitos/metabolismo , MicroRNAs/genética , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Cartilagem Articular/metabolismo , RNA Circular/genética , RNA Circular/metabolismo , Matriz Extracelular/genética , Matriz Extracelular/metabolismo , Homeostase
19.
Parasit Vectors ; 16(1): 30, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36698166

RESUMO

BACKGROUND: Alzheimer's disease presents an abnormal cognitive behavior. TgCtwh6 is one of the predominant T. gondii strains prevalent in China. Although T. gondii type II strain infection can cause host cognitive behavioral abnormalities, we do not know whether TgCtwh6 could also cause host cognitive behavioral changes. So, in this study, we will focus on the effect of TgCtwh6 on mouse cognitive behavior and try in vivo and in vitro to explore the underlying mechanism by which TgCtwh6 give rise to mice cognitive behavior changes at the cellular and molecular level. METHODS: C57BL/6 mice were infected orally with TgCtwh6 cysts. From day 90 post-infection on, all mice were conducted through the open field test and then Morris water maze test to evaluate cognitive behavior. The morphology and number of cells in hippocampus were examined with hematoxylin-eosin (H&E) and Nissl staining; moreover, Aß protein in hippocampus was determined with immunohistochemistry and thioflavin S plaque staining. Synaptotagmin 1, apoptosis-related proteins, BACE1 and APP proteins and genes from hippocampus were assessed by western blotting or qRT-PCR. Hippocampal neuronal cell line or mouse microglial cell line was challenged with TgCtwh6 tachyzoites and then separately cultured in a well or co-cultured in a transwell device. The target proteins and genes were analyzed by immunofluorescence staining, western blotting and qRT-PCR. In addition, mouse microglial cell line polarization state and hippocampal neuronal cell line apoptosis were estimated using flow cytometry assay. RESULTS: The OFT and MWMT indicated that infected mice had cognitive behavioral impairments. The hippocampal tissue assay showed abnormal neuron morphology and a decreased number in infected mice. Moreover, pro-apoptotic proteins, as well as BACE1, APP and Aß proteins, increased in the infected mouse hippocampus. The experiments in vitro showed that pro-apoptotic proteins and p-NF-κBp65, NF-κBp65, BACE1, APP and Aß proteins or genes were significantly increased in the infected HT22. In addition, CD80, pro-inflammatory factors, notch, hes1 proteins and genes were enhanced in the infected BV2. Interestingly, not only the APP and pro-apoptotic proteins in HT22, but also the apoptosis rate of HT22 increased after the infected BV2 were co-cultured with the HT22 in a transwell device. CONCLUSIONS: Neuron apoptosis, Aß deposition and neuroinflammatory response involved with microglia polarization are the molecular and cellular mechanisms by which TgCtwh6 causes mouse cognitive behavioral abnormalities.


Assuntos
Cognição , Toxoplasma , Animais , Camundongos , Secretases da Proteína Precursora do Amiloide/genética , Proteínas Reguladoras de Apoptose/genética , Ácido Aspártico Endopeptidases/genética , Modelos Animais de Doenças , Genótipo , Camundongos Endogâmicos C57BL , Toxoplasma/genética
20.
ACS Appl Mater Interfaces ; 15(1): 292-308, 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36583968

RESUMO

A critical-sized bone defect, which cannot be repaired through self-healing, is a major challenge in clinical therapeutics. The combination of biomimetic hydrogels and nano-hydroxyapatite (nano-HAP) is a promising way to solve this problem by constructing an osteogenic microenvironment. However, it is challenging to generate nano-HAP with a similar morphology and structure to that of natural bone, which limits the improvement of bone regeneration hydrogels. Inspired by our previous works on organic-inorganic cocross-linking, here, we built a strong organic-inorganic interaction by cross-linking periosteum-decellularized extracellular matrix and calcium phosphate oligomers, which ensured the in situ mineralization of bone-like nano-HAP in hydrogels. The resulting biomimetic osteogenic hydrogel (BOH) promotes bone mineralization, construction of immune microenvironment, and angiogenesis improvement in vitro. The BOH exhibited acceleration of osteogenesis in vivo, achieving large-sized bone defect regeneration and remodeling within 8 weeks, which is superior to many previously reported hydrogels. This study demonstrates the important role of bone-like nano-HAP in osteogenesis, which deepens the understanding of the design of biomaterials for hard tissue repair. The in situ mineralization of bone-like nano-HAP emphasizes the advantages of inorganic ionic oligomers in the construction of organic-inorganic interaction, which provides an alternative method for the preparation of advanced biomimetic materials.


Assuntos
Durapatita , Hidrogéis , Durapatita/farmacologia , Durapatita/química , Hidrogéis/farmacologia , Hidrogéis/química , Biomimética , Regeneração Óssea , Osteogênese , Periósteo , Aceleração
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