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1.
Nat Commun ; 13(1): 4583, 2022 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-35933512

RESUMO

Disseminated intravascular coagulation (DIC) is a complication of sepsis currently lacking effective therapeutic options. Excessive inflammatory responses are emerging triggers of coagulopathy during sepsis, but the interplay between the immune system and coagulation are not fully understood. Here we utilize a murine model of intraperitoneal lipopolysaccharide stimulation and show neutrophils in the circulation mitigate the occurrence of DIC, preventing subsequent septic death. We show circulating neutrophils release extracellular vesicles containing mitochondria, which contain superoxide dismutase 2 upon exposure to lipopolysaccharide. Extracellular superoxide dismutase 2 is necessary to induce neutrophils' antithrombotic function by preventing endothelial reactive oxygen species accumulation and alleviating endothelial dysfunction. Intervening endothelial reactive oxygen species accumulation by antioxidants significantly ameliorates disseminated intravascular coagulation improving survival in this murine model of lipopolysaccharide challenge. These findings reveal an interaction between neutrophils and vascular endothelium which critically regulate coagulation in a model of sepsis and may have potential implications for the management of disseminated intravascular coagulation.


Assuntos
Transtornos da Coagulação Sanguínea , Coagulação Intravascular Disseminada , Vesículas Extracelulares , Sepse , Animais , Dacarbazina/uso terapêutico , Modelos Animais de Doenças , Coagulação Intravascular Disseminada/tratamento farmacológico , Coagulação Intravascular Disseminada/etiologia , Lipopolissacarídeos/toxicidade , Camundongos , Neutrófilos , Espécies Reativas de Oxigênio , Superóxido Dismutase
2.
Front Plant Sci ; 13: 926953, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35783953

RESUMO

RNA structure plays key roles in plant growth, development, and adaptation. One of the complex RNA structures is the RNA G-quadruplex (RG4) where guanine-rich sequences are folded into two or more layers of G-quartets. Previous computational predictions of RG4 revealed that it is widespread across the whole transcriptomes in many plant species, raising the hypothesis that RG4 is likely to be an important regulatory motif in plants. Recently, with the advances in both high-throughput sequencing and cell imaging technologies, RG4 can be detected in living cells as well as at the genome-wide scale. Here, we provide a comprehensive review of recent developments in new methods for detecting RG4 in plants. We also summarize the new functions of RG4 in regulating plant growth and development. We then discuss the possible role of RG4 in adapting to environmental conditions along with evolutionary perspectives.

3.
Phys Rev Lett ; 129(1): 016401, 2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35841573

RESUMO

Valence transition could induce structural, insulator-metal, nonmagnetic-magnetic and superconducting transitions in rare-earth metals and compounds, while the underlying physics remains unclear due to the complex interaction of localized 4f electrons as well as their coupling with itinerant electrons. The valence transition in the elemental metal europium (Eu) still has remained as a matter of debate. Using resonant x-ray emission scattering and x-ray diffraction, we pressurize the states of 4f electrons in Eu and study its valence and structure transitions up to 160 GPa. We provide compelling evidence for a valence transition around 80 GPa, which coincides with a structural transition from a monoclinic (C2/c) to an orthorhombic phase (Pnma). We show that the valence transition occurs when the pressure-dependent energy gap between 4f and 5d electrons approaches the Coulomb interaction. Our discovery is critical for understanding the electrodynamics of Eu, including magnetism and high-pressure superconductivity.

4.
Acad Radiol ; 2022 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-35811218

RESUMO

RATIONALE AND OBJECTIVES: This study aimed to explore the effect of iron deposition on native T1 mapping and blood oxygen level-dependent (BOLD) imaging in detecting liver fibrosis (LF) in a rabbit model. MATERIALS AND METHODS: An LF group (n = 100) was established by subcutaneously injecting 50% carbon tetrachloride (CCl4) oil solution, and 20 normal rabbits composed a control group. Native T1 mapping and BOLD were performed, and the T1native and R2* quantitative parameters were analyzed by receiver operating characteristic (ROC) and multiple logistic regression analyses, with histopathological results and liver iron content (LIC) serving as reference standards. RESULTS: In total, 18, 17, 16, 18, and 15 rabbits were histopathologically diagnosed with LF stages F0, F1, F2, F3, and F4, respectively. T1native (r = 0.47), R2* (r = 0.75) and LIC (r = 0.61) increased with LF stage progression (p < 0.001). Compared to T1native values, R2* performed better in diagnosing the LF stage, especially for distinguishing F1-F2 from F3-F4 (AUC = 0.66 vs. 0.91, p = 0.01). Combined with the LIC, both T1native and R2* showed improved diagnostic value in comparison to the individual imaging techniques, particularly for diagnosing F0 vs. F1-F2 and F0 vs. F1-F4, with AUC values of 0.90 vs. 0.70 (p = 0.01) and 0.93 vs. 0.77 (p = 0.01) for T1native + LIC vs. LIC, respectively. CONCLUSION: BOLD imaging performed better than native T1 mapping in predicting and diagnosing LF stage progression. The decrease in diagnostic accuracy caused by the deposition of liver iron is a potential pitfall in the assessment of LF with BOLD imaging and native T1 mapping.

5.
Mol Med Rep ; 26(3)2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35856407

RESUMO

Early­onset epileptic encephalopathy (EOEE) represents one of the most severe epilepsies, characterized by recurrent seizures during early infancy, electroencephalogram (EEG) abnormalities and varying degrees of neurodevelopmental delay. The KCNQ2 gene has been reported to have a major role in EOEE. In the present study, a 3­month­old female infant from the Chinese Lisu minority with EOEE was analyzed. Detailed clinical evaluations and next­generation sequencing were performed to investigate the clinical and genetic characteristics of this patient, respectively. Furthermore, the three­dimensional structure of the mutant protein was predicted by SWISS­Model and the expression of KCNQ2 protein in the patient was assessed by flow cytometry. It was observed that the patient presented with typical clinical features of EOEE, including repeated non­febrile seizures and significant EEG abnormalities. A novel heterozygous missense variant c.431G>C (p.R144P) in KCNQ2 was identified in the patient and the genotyping of KCNQ2 in the patient's parents suggested that this variant was de novo. Subsequently, the breakage of hydrogen bonds between certain amino acids was predicted by structural analysis of the mutant protein. Flow cytometric analysis detected a significant reduction buts not complete loss of native KCNQ2 protein expression in the patient (25.1%). In conclusion, a novel variant in KCNQ2 was confirmed as the genetic cause for EOEE in this patient. The present study expanded the pathogenic mutation spectrum of KCNQ2, enhanced the understanding of the molecular pathogenesis of EOEE and provided novel clues for research on the genotype­phenotype correlation in this disease.


Assuntos
Epilepsia , Canal de Potássio KCNQ2 , Eletroencefalografia , Epilepsia/genética , Epilepsia/metabolismo , Feminino , Heterozigoto , Humanos , Canal de Potássio KCNQ2/genética , Canal de Potássio KCNQ2/metabolismo , Proteínas Mutantes/genética , Proteínas Mutantes/metabolismo , Mutação
6.
J Adv Res ; 2022 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-35811061

RESUMO

INTRODUCTION: Beneficial microorganisms play essential roles in plant growth and induced systemic resistance (ISR) by releasing signaling molecules. Our previous study obtained the crude extract from beneficial endophyte Paecilomyces variotii, termed ZNC (ZhiNengCong), which significantly enhanced plant resistance to pathogen even at 100 ng/ml. However, the immunoreactive components of ZNC remain unclear. Here, we further identified one of the immunoreactive components of ZNC is a nucleoside 2'-deoxyguanosine (2-dG). OBJECTIVES: This paper intends to reveal the molecular mechanism of microbial-derived 2'-deoxyguanosine (2-dG) in activating plant immunity, and the role of plant-derived 2-dG in plant immunity. METHODS: The components of ZNC were separated using a high-performance liquid chromatography (HPLC), and 2-dG is identified using a HPLC-mass spectrometry system (LC-MS). Transcriptome analysis and genetic experiments were used to reveal the immune signaling pathway dependent on 2-dG activation of plant immunity. RESULTS: This study identified 2'-deoxyguanosine (2-dG) as one of the immunoreactive components from ZNC. And 2-dG significantly enhanced plant pathogen resistance even at 10 ng/ml (37.42 nM). Furthermore, 2-dG-induced resistance depends on NPR1, pattern-recognition receptors/coreceptors, ATP receptor P2K1 (DORN1), ethylene signaling but not salicylic acid accumulation. In addition, we identified Arabidopsis VENOSA4 (VEN4) was involved in 2-dG biosynthesis and could convert dGTP to 2-dG, and vne4 mutant plants were more susceptible to pathogens. CONCLUSION: In summary, microbial-derived 2-dG may act as a novel immune signaling molecule involved in plant-microorganism interactions, and VEN4 is 2-dG biosynthesis gene and plays a key role in plant immunity.

7.
Parasite ; 29: 34, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35833784

RESUMO

Blastocystis sp. is a common anaerobic protist with controversial pathogenicity that can infect various animals and humans. However, there are no reports of Blastocystis sp. infections in forest musk deer (Moschus berezovskii). The present study was designed to examine the occurrence, subtype distribution and genetic characterization of Blastocystis sp. in forest musk deer in southwestern China, and to assess the potential for zoonotic transmission. A total of 504 fresh stool samples were collected from captive forest musk deer in four distinct areas of southwestern China. Overall, 14.7% of the forest musk deer (74/504) were found to be infected with Blastocystis sp. The highest occurrence of Blastocystis sp. was observed in Dujiangyan (27.5%), followed by Maerkang (23.3%). The occurrence of Blastocystis sp. was 7.9% and 4.1% in Shimian and Hanyuan, respectively. Significant differences in the occurrence of Blastocystis sp. among different areas were observed (p < 0.05), while we did not observe significant differences among animals of different age and sex (p > 0.05). Two known zoonotic subtypes (ST1 and ST5) and three animal-predominant subtypes (ST10, ST13, and ST14) were identified, of which ST10 was the most common (36/74, 48.6%). Our findings highlight that forest musk deer may be potential reservoirs of zoonotic human Blastocystis sp. infections.


Title: Présence, diversité génétique et potentiel zoonotique de Blastocystis sp. chez le cerf porte-musc (Moschus berezovskii) dans le sud-ouest de la Chine. Abstract: Blastocystis sp. est un protiste anaérobie commun, de pathogénicité controversée, et qui peut infecter divers animaux et les humains. Cependant, aucun cas d'infection par Blastocystis sp. n'a été rapporté chez le cerf porte-musc (Moschus berezovskii). La présente étude a été conçue pour examiner la présence, la distribution des sous-types et la caractérisation génétique de Blastocystis sp. chez le cerf porte-musc du sud-ouest de la Chine et pour évaluer son potentiel de transmission zoonotique. Au total, 504 échantillons de selles fraîches ont été prélevés sur des cerfs porte-musc captifs dans quatre régions distinctes du sud-ouest de la Chine. Dans l'ensemble, 14,7 % (74/504) des cerfs porte-musc se sont avérés infectés par Blastocystis sp. La plus forte occurrence de Blastocystis sp. a été observée à Dujiangyan (27,5 %), suivi de Maerkang (23,3 %). La présence de Blastocystis sp. était respectivement de 7,9 % et 4,1 % à Shimian et Hanyuan. Des différences significatives dans la présence de Blastocystis sp. entre les différentes zones ont été observées (p < 0,05), alors que nous n'avons pas observé de différences significatives entre les animaux d'âge et de sexe différents (p > 0,05). Deux sous-types zoonotiques connus (ST1 et ST5) et trois sous-types à prédominance animale (ST10, ST13 et ST14) ont été identifiés, dont ST10 était le sous-type le plus courant (36/74, 48,6 %). Nos découvertes mettent en évidence que le cerf porte-musc forestier peut être un réservoir potentiel d'infections à Blastocystis sp.


Assuntos
Infecções por Blastocystis , Blastocystis , Cervos , Animais , Blastocystis/genética , Infecções por Blastocystis/epidemiologia , Infecções por Blastocystis/veterinária , China/epidemiologia , Florestas , Variação Genética , Humanos , Receptores Proteína Tirosina Quinases/genética , Receptores Colinérgicos/genética , Zoonoses/epidemiologia
8.
Microbiol Spectr ; : e0226921, 2022 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-35736237

RESUMO

Blastocystis is a common protistan parasite inhabiting the gastrointestinal tract of a wide range of hosts including humans and domestic and wild animals. Many studies have revealed the associations between Blastocystis and gut microbiome in humans. However, only a few studies have focused on the associations between Blastocystis and gut microbiome of animals, especially in forest musk deer (Moschus berezovskii). We investigated the effects of the Blastocystis colonization on the intestinal bacterial community compositions using amplicon sequencing targeting the V4 variable region of the 16S rRNA. Two subtypes of Blastocystis (ST5 and ST10) and Blastocystis-free (control) were included in this study. We found that compared with the forest musk deer without Blastocystis, ST10-colonized forest musk deer had higher bacterial richness and diversity, while ST5-colonized forest musk deer showed a comparable bacterial diversity. Likewise, beta diversity revealed significant differences in bacterial community structure between ST10-colonized and Blastocystis-free forest musk deer. The proportion of Bacteroidetes were significantly enriched in ST10-colonized forest musk deer. Bacterial community structure between ST5-colonized and Blastocystis-free forest musk deer did not differ significantly. The present study explored the associations between Blastocystis and gut microbial community of forest musk deer for the first time, and revealed ST10 colonization, instead of ST5, is associated with higher bacterial diversity and shifted microbial structure. Our data provides valuable insights into the associations between gut microbiomes and parasites. IMPORTANCE Forest musk deer is listed as an endangered species by International Union for Conservation of Nature Red List, and the Chinese government has introduced captivity breeding measures to curb the rapid decline of the musk deer population since the 1950s. It has been suggested that Blastocystis colonization can modulate the composition of the host's intestinal microbiota, thereby affecting the host health. The present study investigated the effects of the Blastocystis colonization on the gut microbiota in the feces of forest musk deer in Sichuan Province, China. Two subtypes (ST5 and ST10) have differential effects on the bacterial diversity and community composition, suggesting that the study of Blastocystis should be distinguished at the subtype level. Because the pathogenicity of Blastocystis is controversial, pathogenic, or commensal, continuous monitoring of the impact of Blastocystis colonization on the intestinal microbiota is of great significance to assess its health effects on forest musk deer.

9.
BMC Genomics ; 23(1): 437, 2022 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-35698044

RESUMO

BACKGROUND: The pigmentation phenotype diversity is rich in domestic goats, and identification of the genetic loci affecting coat color in goats has long been of interest. Via the detections of selection signatures, a duplication upstream ASIP was previously reported to be a variant affecting the Swiss markings depigmentation phenotype in goats. RESULTS: We conducted a genome-wide association study using whole-genome sequencing (WGS) data to identify the genetic loci and causal variants affecting the pigmentation phenotype in 65 Jintang black (JT) goats (i.e., 48 solid black vs. 17 non-classic Swiss markings). Although a single association peak harboring the ASIP gene at 52,619,845-72,176,538 bp on chromosome 13 was obtained using a linear mixed model approach, all the SNPs and indels in this region were excluded as causal variants for the pigmentation phenotype. We then found that all 17 individuals with non-classic Swiss markings carried a 13,420-bp duplication (CHI13:63,129,198-63,142,617 bp) nearly 101 kb upstream of ASIP, and this variant was strongly associated (P = 1.48 × 10- 12) with the coat color in the 65 JT goats. The copy numbers obtained from the WGS data also showed that the duplication was present in all 53 goats from three European breeds with Swiss markings and absent in 45 of 51 non-Swiss markings goats from four other breeds and 21 Bezoars, which was further validated in 314 samples from seven populations based on PCR amplification. The copy numbers of the duplication vary in different goat breeds with Swiss markings, indicating a threshold effect instead of a dose-response effect at the molecular level. Furthermore, breakpoint flanking repeat analysis revealed that the duplication was likely to be a result of the Bov-B-mediated nonallelic homologous recombination. CONCLUSION: We confirmed that a genomic region harboring the ASIP gene is a major locus affecting the coat color phenotype of Swiss markings in goats. Although the molecular genetic mechanisms remain unsolved, the 13,420-bp duplication upstream of ASIP is a necessary but not sufficient condition for this phenotype in goats. Moreover, the variations in the copy number of the duplication across different goat breeds do not lead to phenotypic heterogeneity.


Assuntos
Estudo de Associação Genômica Ampla , Cabras , Animais , Genoma , Cabras/genética , Fenótipo
10.
J Comput Assist Tomogr ; 46(3): 383-391, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35575651

RESUMO

MATERIALS AND METHODS: The PubMed, Web of Science, Embase, and the Cochrane Library databases were searched up to January 2021 to identify original studies that investigated the accuracy of individual DCE-MRI features in differentiating malignant from benign breast lesions. Pooled sensitivity, specificity, and area under the curve were calculated by STATA software based on the data extracted from included studies. Moreover, quality assessment, subgroup analysis, and publication bias evaluation were performed. RESULTS: Twenty-nine studies comprising 2976 patients and 3365 suspicious breast lesions were included. Malignant breast lesions tended to present irregular shapes (83.59%), noncircumscribed margins (85.50%), mass enhancement (52.31%), heterogeneous internal enhancement (71.72%), and type II or III time intensity curve (TIC) patterns (91.17%), showing significant differences compared with benign breast lesions (P < 0.05). For differentiating malignant from benign breast lesions, the area under the curve values of irregular shape, noncircumscribed margin, mass enhancement, heterogeneous internal enhancement, and type II or III TIC patterns were 0.79 (0.76-0.83), 0.87 (0.84-0.90), 0.63 (0.58-0.67), 0.82 (0.78-0.85), and 0.89 (0.86-0.92), respectively. CONCLUSIONS: Imaging features derived from DCE-MRI, especially TIC patterns, are important for diagnosing and differentiating malignant from benign breast lesions.


Assuntos
Neoplasias da Mama , Meios de Contraste , Mama/diagnóstico por imagem , Mama/patologia , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Diagnóstico Diferencial , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Estudos Retrospectivos , Sensibilidade e Especificidade
11.
Plant Commun ; 3(3): 100324, 2022 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-35576156

RESUMO

Xanthomonas oryzae pv. oryzicola (Xoc), which causes rice bacterial leaf streak, invades leaves mainly through stomata, which are often closed as a plant immune response against pathogen invasion. How Xoc overcomes stomatal immunity is unclear. Here, we show that the effector protein AvrRxo1, an ATP-dependent protease, enhances Xoc virulence and inhibits stomatal immunity by targeting and degrading rice OsPDX1 (pyridoxal phosphate synthase), thereby reducing vitamin B6 (VB6) levels in rice. VB6 is required for the activity of aldehyde oxidase, which catalyzes the last step of abscisic acid (ABA) biosynthesis, and ABA positively regulates rice stomatal immunity against Xoc. Thus, we provide evidence supporting a model in which a major bacterial pathogen inhibits plant stomatal immunity by directly targeting VB6 biosynthesis and consequently inhibiting the biosynthesis of ABA in guard cells to open stomata. Moreover, AvrRxo1-mediated VB6 targeting also explains the poor nutritional quality, including low VB6 levels, of Xoc-infected rice grains.


Assuntos
Oryza , Proteínas de Bactérias , Oryza/genética , Oryza/metabolismo , Doenças das Plantas/microbiologia , Vitamina B 6 , Xanthomonas
12.
Nanomaterials (Basel) ; 12(9)2022 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-35564226

RESUMO

The first part of the current review highlights the evolutionary nuances and research hotspots in the field of nanoparticles in low carbon fuels. Our findings reveal that contribution to the field is largely driven by researchers from Asia, mainly India. Of the three biofuels under review, biodiesel seems to be well studied and developed, whereas studies regarding vegetable oils and alcohols remain relatively scarce. The second part also reviews the application of nanoparticles in biodiesel/vegetable oil/alcohol-based fuels holistically, emphasizing fuel properties and engine characteristics. The current review reveals that the overall characteristics of the low carbon fuel-diesel blends improve under the influence of nanoparticles during combustion in diesel engines. The most important aspect of nanoparticles is that they act as an oxygen buffer that provides additional oxygen molecules in the combustion chamber, promoting complete combustion and lowering unburnt emissions. Moreover, the nanoparticles used for these purposes exhibit excellent catalytic behaviour as a result of their high surface area-to-volume ratio-this leads to a reduction in exhaust pollutants and ensures an efficient and complete combustion. Beyond energy-based indicators, the exergy, economic, environmental, and sustainability aspects of the blends in diesel engines are discussed. It is observed that the performance of the diesel engine fuelled with low carbon fuels according to the second law of efficiency improves under the influence of the nano-additives. Our final part shows that despite the benefits of nanoparticles, humans and animals are under serious threats from the highly toxic nature of nanoparticles.

13.
Biotechnol Lett ; 44(7): 845-855, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35614284

RESUMO

Hfq is an RNA-binding protein, its main function is to participate in post-transcriptional regulation of bacteria and regulate small regulatory RNA (sRNA) and messenger RNA (mRNA) stability, but the Hfq function of Bacillus subtilis (B. subtilis) has not been fully explained. In this study, we used the strains of B. subtilis168 (BS168), BS168Δhfq and BS168Δhfq-C to explore the effects of Hfq on the glucose utilization, biofilm formation and quorum sensing (QS) system of B. subtilis. The results showed that the knockout of hfq resulted in growth defects when bacteria were cultured in the Luria-Bertani (LB) medium, but we did not observe the same effects in Nitrogen medium (NM) and Inorganic Salt-free medium (ISM). We further found that the growth of strains under different glucose concentrations was also different, which was related to the expression of CcpA. Interestingly, the hfq mutant showed increased resistance to a high-glucose environment. Furthermore, the biofilm and extracellular poly saccharides (EPS) formation of BS168Δhfq decreased significantly. At the same time, changes were observed in the morphology of the biofilm, such as larger intercellular space of the biofilm and thinner edge. The qRT-PCR results confirmed that the hfq knockout caused significant up-regulation or down-regulation of gene expression in QS system, and down-regulated genes were involved in the positive regulation of biofilm formation. Taken together, we demonstrated that Hfq plays a vital role in glucose utilization, biofilm formation and QS of B. subtilis, which provides a new perspective for subsequent related research.


Assuntos
Bacillus subtilis , Percepção de Quorum , Bacillus subtilis/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Biofilmes , Regulação Bacteriana da Expressão Gênica , Glucose/metabolismo , Percepção de Quorum/genética
15.
ACS Omega ; 7(14): 11799-11808, 2022 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-35449981

RESUMO

The crystal growth process has an important influence on the viscosity of the slag, which affects the characteristics of the slag layer on the wall of the gasifier. The slag flow and heat transfer model based on temperature-time-viscosity of crystalline slag were established, to predict the slag behaviors and protect gasifier. The results showed the overall viscosity of the slag after considering the residence time effect was higher than that when using the measured viscosity-temperature curve value. The liquid slag thickness, solid slag thickness, and residence time increased after the slag viscosity amendment, while the slag flow velocity and heat flux density decreased. Moreover, several types of crystallized slag were constructed to study the effects of crystal morphology and degree of crystallization difficulty on slag behaviors. The result indicated that the difficulty and crystal morphology of the slag crystallization cannot be ignored when using crystallized slag in gasification.

16.
Int J Biol Macromol ; 209(Pt A): 1516-1525, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35452701

RESUMO

Elevated expressions of transforming growth factor ß1 (TGF-ß1) have been implicated in the pathogenesis of liver fibrosis, thus attenuating the excessive TGF-ß1's activity by TGF-ß1-binding peptide is an ideal strategy for the treatment of liver fibrosis. However, the application of small peptide as a pharmaceutical agent is obstacle due to difficult preparation and non-selective delivery. The I-plus sequences of circumsporozoite protein (CSP-I) possesses high affinity for heparan sulfate proteoglycans, which are primarily located on liver tissues. TGF-ß1-binding peptide P15 holds specific ability of binding to TGF-ß1. In this study, we describe an approach to efficiently preparing liver-targeting peptide P15-CSP-I, which is conjugation of the sequences of P15 to the N-terminus of CSP-I, from the cleavage of biological macromolecule SUMO-tagged P15-CSP-I. In vitro and ex vivo binding assay showed that P15-CSP-I specifically targeted to the hepatocytes and liver tissues. Moreover, P15-CSP-I inhibited cell proliferation, migration and invasion, and decreased fibrosis-related proteins expression in TGF-ß1-activated HSCs in vitro. Furthermore, P15-CSP-I ameliorated liver morphology and decreased the fibrosis responses in vivo. Taken together, P15-CSP-I may be a potential candidate for targeting therapy on liver fibrosis due to its high efficient preparation, specific liver-targeting potential and improved anti-liver fibrotic activity.


Assuntos
Proteoglicanas de Heparan Sulfato , Fígado , Fator de Crescimento Transformador beta1 , Animais , Proteoglicanas de Heparan Sulfato/metabolismo , Humanos , Fígado/metabolismo , Cirrose Hepática/patologia , Camundongos , Peptídeos/metabolismo , Ratos , Proteína SUMO-1/metabolismo , Fator de Crescimento Transformador beta1/metabolismo
17.
J Biomater Sci Polym Ed ; : 1-20, 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35446748

RESUMO

A glucose-sensitive antibacterial and anti-inflammatory hydrogel film with controlled release of tannic acid (TA) was synthesized using chitosan (CS). Specifically, the photo-crosslinked CS hydrogel was first obtained and then immersed in TA solution to generate composite hydrogel film with enhanced mechanical properties. Subsequently, N-hydroxysuccinimide/1-ethyl-3-(3-dimethylaminopropyl) carbodiimide based coupling chemistry was used to covalently crosslink glucose oxidase (GOx) to CS to obtain glucose sensitivity. The physicochemical properties, including chemical composition, enzyme-related characteristics, glucose responsiveness, and mechanical strength, were thoroughly investigated, followed by the cytotoxicity, antibacterial and anti-inflammatory tests. The results showed that the GOx immobilized on the film surface by covalent bonding gave better stability than those that were physically adsorbed. In addition, it could quickly and correspondingly modify its inner pore structure in response to the glucose stimulus and then control the loaded TA release. Meanwhile, the TA addition could enhance the film's mechanical properties. The composite hydrogel film demonstrated adequate biocompatibility and can inhibit NO, IL-6, and TNF-α production in stimulated macrophages, as well as Porphyromonas gingivalis growth, demonstrating effective antibacterial and anti-inflammatory activity.

18.
Front Microbiol ; 13: 846747, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35242124

RESUMO

Porcine deltacoronavirus (PDCoV) is an emerging porcine intestinal coronavirus in recent years, which mainly causes different degrees of vomiting and diarrhea in piglets and has caused great harm to the swine husbandry worldwide since its report. Selenium is an essential trace element for organisms and has been demonstrated to have antiviral effects. In this study, pig kidney epithelial (LLC-PK) cells were used to study the antiviral activity of selenomethionine (Se-Met) (2, 4, 8, and 16 µM) against PDCoV by detecting the replication of the virus, the expression of the mitochondrial antiviral signal protein (MAVS) protein, and the phosphorylation of interferon regulatory factor-3 (IRF-3), IFN-α, and IFN-ß, and the changes in glutathione content, glutathione peroxidase, superoxide dismutase activity, and hydrogen peroxide content in the cells. The results showed that Se-Met at higher than physiological concentrations (16 µM) could significantly inhibit the replication of PDCoV in LLC-PK cells and enhance the expression of MAVS protein and the phosphorylation of IRF-3. In addition, Se-Met also improved the intracellular production of IFNα/ß and antioxidant capacity with increasing doses. These data suggest that the availability of selenium through selenomethionine supports the antiviral response in porcine kidney cells, and the specific mechanism is attributed to the improved cellular antioxidant capacity and activation of the MAVS pathway by Se-Met.

19.
Int J Rheum Dis ; 25(5): 532-562, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35244339

RESUMO

AIM: To provide a systematic analysis of the study design in knee osteoarthritis (OA) preclinical studies, focusing on the characteristics of animal models and cell doses, and to compare these to the characteristics of clinical trials using mesenchymal stem cells (MSCs) for the treatment of knee OA. METHOD: A systematic and comprehensive search was conducted using the PubMed, Web of Science, Ovid, and Embase electronic databases for research papers published in 2009-2020 on testing MSC treatment in OA animal models. The PubMed database and ClinicalTrials.gov website were used to search for published studies reporting clinical trials of MSC therapy for knee OA. RESULTS: In total, 9234 articles and two additional records were retrieved, of which 120 studies comprising preclinical and clinical studies were included for analysis. Among the preclinical studies, rats were the most commonly used species for modeling knee OA, and anterior cruciate ligament transection was the most commonly used method for inducing OA. There was a correlation between the cell dose and body weight of the animal. In clinical trials, there was large variation in the dose of MSCs used to treat knee OA, ranging from 1 × 106 to 200 × 106 cells with an average of 37.91 × 106 cells. CONCLUSION: Mesenchymal stem cells have shown great potential in improving pain relief and tissue protection in both preclinical and clinical studies of knee OA. Further high-quality preclinical and clinical studies are needed to explore the dose effectiveness relationship of MSC therapy and to translate the findings from preclinical studies to humans.


Assuntos
Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Osteoartrite do Joelho , Animais , Ligamento Cruzado Anterior , Humanos , Injeções Intra-Articulares , Transplante de Células-Tronco Mesenquimais/métodos , Osteoartrite do Joelho/terapia , Ratos
20.
Appl Opt ; 61(4): 995-1000, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-35201074

RESUMO

The output performance of the spaceborne fiber amplifier will degrade when exposed to radiation in aerospace environment. In this work, we have proposed a two-stage erbium-ytterbium-co-doped fiber amplifier (EYDFA) and studied the degradation performance under irradiation and recovery through the annealing process without employing any additional device. An irradiation experiment is conducted to test the performances of the amplifier under the irradiation environment, and experimental results indicate that the output power as well as optical signal-to-noise ratio (OSNR) exhibit similar irradiation responses. The amplifier was annealed through photobleaching and natural annealing processes. The output performance almost recovers to its initial level, and it is verified that the annealing efficiency for high intensity photobleaching is about 240 times as much as that for the case of natural annealing. This work confirms that the spaceborne fiber amplifier could achieve performance recovery after being irradiated, which is beneficial to the enhancement of the radiation hardness for future spaceborne fiber optical devices.

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