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1.
Biol Pharm Bull ; 45(5): 569-575, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35491161

RESUMO

Spinal cord injury (SCI) is a disastrous event that often leads to permanent neurological deficits involving motor, sensory, and autonomic dysfunctions in patients. Accumulating research has demonstrated that riluzole may play crucial roles in the process of spinal tissue repair, but the underlying mechanisms remain elusive. This study verified the effectiveness of riluzole and speculated that a riluzole-afforded protection mechanism may be associated with the glycogen synthase kinase-3 beta (GSK-3ß)/collapsin response mediator protein-2 (CRMP-2) pathway in rats after spinal cord injury. Here, a modified Allen's weight dropping model was generated and riluzole at 4 mg/kg was injected intraperitoneally after surgery and twice a day for 7 consecutive days. At 6 weeks after SCI, we found that riluzole treatment reduced the central cavity size of the spinal cord and improved neurological functions. Meanwhile, riluzole-treated rats exhibited shorter latency and larger amplitude in motor evoked potentials and somatosensory evoked potentials, compared with vehicle-treated rats. Furthermore, Western blotting and immunofluorescence data revealed that the expression levels of GSK-3ß and phosphorylated-GSK-3ß were lower in riluzole-treated SCI rats compared with vehicle-treated rats. We next detected the expression CRMP-2 and phosphorylated CRMP-2 and found that the expression of CRMP-2 showed no difference between the riluzole-treated and vehicle-treated groups; however, administration of riluzole downregulated phosphorylated CRMP-2 expression. The current findings suggest that after SCI, administration of riluzole promotes neurological functional restoration, which may be associated, in part, with its activation of the GSK-3ß/CRMP-2 signaling pathway.


Assuntos
Riluzol , Traumatismos da Medula Espinal , Animais , Glicogênio Sintase Quinase 3 beta , Humanos , Peptídeos e Proteínas de Sinalização Intercelular , Proteínas do Tecido Nervoso , Neuritos , Ratos , Riluzol/farmacologia , Riluzol/uso terapêutico , Traumatismos da Medula Espinal/tratamento farmacológico
2.
Front Immunol ; 13: 804945, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35572594

RESUMO

The outbreak of COVID-19 (caused by SARS-CoV-2) has posed a significant threat to global public health security because of its high pathogenicity and infectivity. To date, the pathogenic mechanism of this novel coronavirus (SARS-CoV-2) is still unclear, and there is no effective treatment. As one of the most effective strategies to prevent viral infection, vaccines have become a research hotspot. Based on the current understanding of SARS-CoV-2, the research and development of its vaccines cover almost all forms of current vaccine research, including inactivated vaccines, recombinant protein vaccines, viral vector vaccines, and nucleic acid vaccines. Moreover, with the spread of the new mutant virus, it is necessary to evaluate the protection rate of previous administered vaccines. This article reviews the candidate targets, vaccine types, research and development status, progress of SARS-CoV-2 vaccines, and the effectiveness of neutralizing antibodies against SARS-CoV-2 mutants (B.1.1.7, B.1.351, P.1, B.1.617.2, and B.1.1.529) induced by these vaccines, to provide a reference for follow-up research and prevention.

3.
Artigo em Inglês | MEDLINE | ID: mdl-35436198

RESUMO

This article studies the meaning of parameters of fully connected neural networks with single hidden layer from the perspective of spectrum. Under the constraints of numerical range, the corresponding relationship between parameters and the spectrum of network function can be established by the Fourier series coefficients of the activation function, which is truncated and periodically extended. This work is substantiated on the Mixed National Institute of Standards and Technology (MNIST) handwritten dataset and two illustrative examples with certain spectra. The simulations complete the conversion between spectrum and parameters with high precision and give the significance of hidden nodes to the spectrum of network function. Some algorithms derived from these properties, such as the parameter initialization method using spectrum and the pruning method by sorting amplification weights, are also presented to introduce how spectrum analysis affects neural network decision-making. Thus, spectrum analysis has great potential in network interpretation.

4.
Drug Des Devel Ther ; 16: 1067-1082, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35450403

RESUMO

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) currently poses a threat to human health. 3C-like proteinase (3CLpro) plays an important role in the viral life cycle. Hence, it is considered an attractive antiviral target protein. Whole-genome sequencing showed that the sequence homology between SARS-CoV-2 3CLpro and SARS-CoV 3CLpro is 96.08%, with high similarity in the substrate-binding region. Thus, assessing peptidomimetic inhibitors of SARS-CoV 3CLpro could accelerate the development of peptidomimetic inhibitors for SARS-CoV-2 3CLpro. Accordingly, we herein discuss progress on SARS-CoV-2 3CLpro peptidomimetic inhibitors. Inflammation plays a major role in the pathophysiological process of COVID-19. Small-molecule compounds targeting 3CLpro with both antiviral and anti-inflammatory effects are also briefly discussed in this paper.


Assuntos
COVID-19 , Peptidomiméticos , Anti-Inflamatórios/farmacologia , Antivirais/uso terapêutico , COVID-19/tratamento farmacológico , Proteases 3C de Coronavírus , Humanos , Peptídeo Hidrolases , Peptidomiméticos/farmacologia , Inibidores de Proteases/química , Inibidores de Proteases/farmacologia , SARS-CoV-2
5.
Plant Cell Environ ; 2022 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-35394681

RESUMO

Salicylic acid (SA) is a crucial hormone involved in plant immunity. Rice (Oryza sativa) maintains high SA levels that are not induced by pathogens. However, the roles of SA in rice immunity and yield remain largely unknown. Here, we identified SA 5-hydroxylases 1 (OsS5H1) and 2 (OsS5H2) as the primary enzymes engaged in catalysing SA to 2,5-dihydroxybenzoic acid (2,5-DHBA) in rice. SA levels were significantly increased in the oss5h mutants, while they were dramatically decreased in the OsS5H1 and OsS5H2 overexpression lines. The mutants were resistant, whereas the overexpression lines were susceptible to Pyricularia oryzae and Xanthomonas oryzae pv. Oryzae. Moreover, the pathogen-associated molecular patterns-triggered immunity responses, including reactive oxygen species burst and callose deposition, were enhanced in all the mutants and compromised in the overexpression lines. Quantification of the agronomic traits of the oss5h mutants grown in the paddy fields demonstrated that the grain number per panicle was decreased as the SA levels increased; however, the tiller number and grain size were enhanced, resulting in no significant yield penalty. Collectively, we reveal that mildly increasing SA content in rice can confer broad-spectrum resistance without yield penalty and put new insights into the roles of SA in immunity and growth.

6.
Anal Biochem ; 648: 114679, 2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35367217

RESUMO

Interstitial lung disease (ILD) is the most common complication of rheumatoid arthritis (RA), which highly increases the morbidity and mortality of RA. Lycopodii herba (SJC) has been used as a widespread traditional Chinese medicine to treat RA and the related complications for more than 500 years. However, its therapeutic effect on RA-ILD and related mechanisms are not clear. The purpose of this work was to confirm the efficacy of SJC for RA-ILD and clarify its mechanism. In this study, we first determined the efficacy of SJC on RA-ILD. Then, 15 potential biomarkers of SJC were identified by metabolomics in rat serum, which were mainly associated with ether lipid metabolism and arachidonic acid metabolism. 21 pathways were related to SJC by network pharmacology. Combined with the results of metabolomics and network pharmacology and real-time PCR (RT-PCR) validation, the mechanism of SJC for RA-ILD may be related to the Ras signaling pathway and PI3K-Akt signaling pathway by regulating the expression of PLA2G1B and PI3KCA. This work preliminary confirmed the preventive and therapeutic effects of SJC on RA-ILD and elucidated the mechanism from the metabolic perspective.


Assuntos
Artrite Reumatoide , Doenças Pulmonares Intersticiais , Animais , Artrite Reumatoide/tratamento farmacológico , Medicamentos de Ervas Chinesas , Doenças Pulmonares Intersticiais/complicações , Metabolômica , Fosfatidilinositol 3-Quinases/uso terapêutico , Ratos
7.
Artigo em Inglês | MEDLINE | ID: mdl-35488101

RESUMO

microRNA (miRNA) is a type of endogenous short-chain non-coding RNA with regulatory function found in eukaryotes, which is involved in the regulation of a variety of cellular and biological processes. However, the research on the development of cashmere goat secondary hair follicles is still relatively scarce. In this study, small RNA libraries and mRNA libraries of 45 days, 55 days, 65 days, and 75 days of fetal skin of cashmere goats were constructed, and the constructed libraries were sequenced using Illumina Hiseq4000, and the expression profiles of miRNA and mRNA in cashmere goat fetal skin were obtained. The differentially expressed miRNAs and mRNAs in six control groups were identified and the qRT-PCR experiment shows that the sequencing results are accurate. Sixty-six miRNAs related to secondary hair follicle development were screened, and used TargetScan and miRanda to predict 33 highly expressed miRNA target genes. At the same time, 664 mRNAs related to the development of secondary hair follicles were screened, and GO enrichment and KEGG pathway analysis were performed. It was found that some miRNA target genes were consistent with the screening results of mRNAs related to secondary hair follicle development and were enriched in Notch signaling pathway, TGF-ß signaling pathway. Therefore, miR-145-5p-DLL4, miR-27b-3p-DLL4, miR-30e-5p-DLL4, miR-193b-3p-TGF-ß1, miR-181b-5p-NOTCH2, and miR-103-3p-NOTCH2 regulatory network related to the development of secondary hair follicles were constructed and the results of dual-luciferase reporter gene assay indicated that there is a targeted relationship between chi-miR-30e-5p and DLL4, which will provide a basis for molecular mechanism of miRNA-mRNA in the development of the hair follicles in cashmere goats.

8.
Am J Clin Nutr ; 2022 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-35460222

RESUMO

BACKGROUND: The relation of long-term dietary folate intake with incident chronic kidney disease (CKD) remains uncertain. OBJECTIVE: We aimed to investigate the association between dietary folate intake and incident CKD in a 30-y follow-up study from young adulthood to midlife. METHODS: A total of 4038 American adults aged 18-30 years and without reduced estimated glomerular filtration rate (eGFR) were enrolled in 1985-1986 and monitored until 2015-2016 in the Coronary Artery Risk Development in Young Adults (CARDIA) study. Diet was assessed by a validated dietary-history questionnaire at baseline, in 1992-1993, and in 2005-2006. The primary outcome was incident CKD, defined as an eGFR <60mL/min per 1.73 m2 or urinary albumin to creatinine ratio (ACR) ≥30mg/g. The secondary outcomes included: (1) incident decreased eGFR, defined as an eGFR <60mL/min/1.73 m2, and (2) incident albuminuria, defined as an ACR ≥30mg/g. RESULTS: During the follow-up, 642 (15.9%) participants developed CKD. Overall, there was a significant L-shaped relation of dietary folate with incident CKD after adjustment for potential confounders. Compared with the lowest quintile of total folate intake, the multivariable-adjusted hazard ratios (95%CI) in quintile 2-5 were 0.69(0.56, 0.85), 0.35(0.27, 0.45), 0.34(0.26, 0.45), and 0.39(0.30, 0.51), respectively. Similar results were found for the secondary outcomes. Moreover, the L-shaped association was confirmed in a subset of the cohort (n=1462) with serum folate measured at baseline, and in 1992 and 2000. CONCLUSIONS: Higher folate intake in young adulthood was longitudinally associated with a lower incidence of CKD later in life. Additional studies are warranted to establish the causal inference.

9.
Foods ; 11(7)2022 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-35407074

RESUMO

Applications for vanilla essential oil extracted from vanilla pods have been limited since the effective components of vanilla could be easily influenced by environmental factors, such as temperature, light, and oxygen, which hinder their effectiveness. In this study, vanilla essential oil was encapsulated in a Pickering emulsion with octenyl succinic acid starch (OSA-starch). The optimal process conditions for emulsion preparation were determined as 5% vanilla essential oil phase with 2.5% OSA-starch when they were ultrusonicated for 3 min at 470 W. Under these conditions, the minimum particle size was 0.456 µm, the oil droplets were completely encased by starch, and no new chemical bonds were formed. The smallest particle size was produced at a pH of 4 and 500 mM ion concentration. The antioxidant activity of the emulsion was greater than that of the pure vanilla oil at the same oil content. After 24 h storage, the antioxidant activity of the emulsion was enhanced, and the vanilla essential oil was slowly released in the emulsion. These results indicated that the vanilla essential oil encapsulated in a Pickering emulsion with octenyl succinic acid starch showed its tremendous potential for use in the food industry.

10.
Artigo em Inglês | MEDLINE | ID: mdl-35270386

RESUMO

As one of the typical farmland ecosystems, tea gardens are of vital importance in China. The purpose of this study was to quantify the dynamic of soil properties, soil microbial diversity, and nematodes, as affected by various cover crop patterns in a Tanjiawan tea garden in Hubei Province, China. Four cover crop patterns were established as following: naturally covered of bare land and mixed planting with two species, four species, and eight species. The results revealed that soil organic matter, pH, and total phosphorous content were significantly related to cover crop patterns. The number of nematodes increased with cover crop diversity, and the percentage of plant parasitic nematodes in cover crop treatments was lower than in naturally covered bare land. A higher diversity of cover crops increased the number of bacterivores and fungivores, thereby enhancing the bacterial decomposition pathway of soil organic matter. Both soil nematodes and microbial communities showed significant seasonal changes under different cover crop patterns. The soil food webs were more stable and mature under cover crops with two species and four species. Combined with the results of a structural equation model, we found that soil properties, characterized by the total nitrogen, available phosphorus, NO3--N, and soil organic matter, were significantly correlated with soil nematodes and microbial communities. In addition, acterivores and plant parasites were significantly negatively correlated with omnivores/predators. Our results implied that soil properties and seasonal changes influence the relationships between cover crops, soil nematodes, and microbial communities. These findings provide a theoretical basis for future studies on interactions between soil properties, soil microorganisms, and nematodes in tea gardens.


Assuntos
Nematoides , Solo , Animais , China , Produtos Agrícolas , Ecossistema , Microbiologia do Solo , Chá
11.
Open Med (Wars) ; 17(1): 527-535, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35350833

RESUMO

Several studies reported that the expression of SIRT1 was associated with the clinical features of patients with esophageal squamous cell carcinoma (ESCC), but the function remains inconsistent. We conducted this study to illustrate the clinical value of SIRT1 expression in the early diagnosis and prediction of prognosis of ESCC. In this study, PubMed, Embase, and Web of Science were searched by two independent researchers and STATA14.0 software was used to conduct meta-analysis. The odds ratio with 95% confidence interval was used to estimate the pooled effect. Egger's test and Begg's funnel were used to assess publication bias. Sensitivity analysis was used to evaluate the reliability and stability of meta-analysis results. According to the inclusion and exclusion criteria, six studies were enrolled, including 811 cases of ESCC. Results of the meta-analysis indicated that SIRT1 was overexpressed in ESCC and the SIRT1 expression was closely related to the clinicopathological features of ESCC, such as tumor infiltration, tumor node metastasis (TNM) stage, and lymph node metastasis. In the survival analysis, high expression of SIRT1 represented a poor prognosis in ESCC patients. Our study demonstrated that SIRT1 was overexpressed in ESCC, and it might be a potential biomarker for progress of ESCC.

12.
Am J Dent ; 35(1): 55-60, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35316594

RESUMO

PURPOSE: To investigate the effect of type 2 diabetes mellitus (T2DM) and periodontitis on the Th1/Th2/Th17/Treg paradigm. METHODS: A total of 107 volunteers (aged 18-78 years) were recruited. Peripheral blood samples from patients with periodontitis and T2DM (n= 43), patients with periodontitis only (n= 20), patients with T2DM only (n= 23), and healthy controls (n= 21) were collected. Blood pressure, glycated hemoglobin, fasting plasma glucose, probing depth, gingival index, and clinical attachment loss were measured. The circulating proportions of Th1, Th2, Th17, and Treg cells were estimated by flow cytometry. The data were analyzed by a 2x2 factorial ANOVA. RESULTS: We observed higher ratios of Th1/Th2 and Th17/Treg cells among patients with T2DM (P< 0.05) than among healthy controls. The proportion of Th17 cells in patients with periodontitis and T2DM was higher than that in other groups (P< 0.05). T2DM exhibited a predominant effect on the proportion of Th1 cells (F= 18.127, P= 0.000) and the Th17/Treg ratio (F= 45.384, P= 0.000). A significant "T2DM x periodontitis" interaction effect on the proportion of Th2, Th17, Treg cells, and the Th1/Th2 ratio (P< 0.05) was also noticed. The area under curve of Th17 was 0.711 (95% CI= 0.584 to 0.803, P< 0.01) in the receiver operating characteristic curve analysis. CLINICAL SIGNIFICANCE: The results suggest that the proportion of Th2, Th17, Treg cells and the Th1/Th2 ratio is indicative of immune activation and inflammation, which are evident in patients with type 2 diabetes mellitus (T2DM) and periodontitis. The data indicate that the high expression of Th17 cells may be a relevant biological factor that can be associated with an increased risk of developing chronic periodontitis in patients with T2DM.


Assuntos
Diabetes Mellitus Tipo 2 , Periodontite , Adolescente , Adulto , Idoso , Diabetes Mellitus Tipo 2/metabolismo , Humanos , Pessoa de Meia-Idade , Linfócitos T Reguladores/metabolismo , Células Th1/metabolismo , Células Th17/metabolismo , Adulto Jovem
13.
Int J Legal Med ; 2022 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-35316386

RESUMO

Papaver somniferum L. (opium poppy) is the original plant of heroin, which is a major narcotic drug, and this plant has brought great harm to human health. However, the ban on opium poppy cultivation and trafficking is facing great challenges because of abnormal profits. Therefore, rapid and accurate identification is important to address the abovementioned problems. In this study, eleven simple sequence repeats (SSR) markers and two single nucleotide polymorphism (SNP) markers were mined to distinguish opium poppy from other six Papaver species. These molecular markers were further verified through a large number of plant materials of these seven Papaver species. An excellent multiplex polymerase chain reaction (PCR) system that simultaneously amplifies the three of eleven SSR markers was developed, which effectively improves the efficiency and speed of identification. The present research is of great implication for identifying and investigating the illegal cultivation and trafficking of opium poppy.

14.
Phytomedicine ; 99: 154000, 2022 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-35235888

RESUMO

BACKGROUND: Cognitive dysfunction is commonly observed in diabetic patients, yet, the underlying mechanisms are obscure and there are no approved drugs. Skeletal muscle is a key pathological organ in diabetes. Evidence is accumulating that skeletal muscle and brain communication are important for cognitive, and kynurenine (KYN) metabolism is one of the mediators. PURPOSE: This study aims to elucidate the mechanism of diabetes-induced cognitive impairment (DCI) from the perspective of skeletal muscle and brain communication, and to explore the therapeutic effect of Zi Shen Wan Fang (ZSWF, a optimized prescription consists of Anemarrhenae Rhizoma (Anemarrhena asphodeloides Bge.), Phellodendri Chinensis Cortex (Phellodendron chinense Schneid.) and Cistanches Herba (Cistanche deserticola Y.C.Ma)), in order to provide new strategies for the prevention and treatment of DCI and preliminarily explore valuable drugs. METHODS: DCI was induced by intraperitoneal injection of streptozotocin (STZ) combined with a high-fat diet and treated with different dosage ZSWF extract by oral gavage for 8 weeks, once a day. Cognitive and skeletal muscle function was assessed, synaptic plasticity and L-type amino acid transporter (LAT1) was measured. KYN and its metabolites as well as metabolic enzymes in the hippocampus, peripheral blood and skeletal muscle were measured. Peroxisome proliferator-activated receptor-γ co-activator-1α (PGC-1α) and peroxisome proliferator-activated receptor α (PPARα) were measured in skeletal muscle. RESULTS: Compared with healthy mice, DCI mice not only showed decreased cognitive function and abnormal skeletal muscle function, but also showed imbalance of KYN metabolism in brain, circulating blood and skeletal muscle. Fortunately, ZSWF administration for 8 weeks notably attenuated the cognitive function, synaptic plasticity and skeletal muscle function in DCI mice. Besides, ZSWF significantly attenuated KYN metabolism in brain, circulation and skeletal muscle of DCI mice. Furthermore, ZSWF activated PGC1α-PPARα in skeletal muscle of DCI mice. CONCLUSIONS: These results indicate that abnormal PGC1α-PPARα signaling in skeletal muscle mediating KYN metabolism disorder is one of the pathological mechanisms of DCI, and ZSWF can reverse diabetes-induced cognitive impairment via activating skeletal muscle PGC1α-PPARα signaling to maintain KYN metabolism homeostasis.

15.
Anal Chem ; 94(12): 4901-4905, 2022 03 29.
Artigo em Inglês | MEDLINE | ID: mdl-35285614

RESUMO

The biodistribution of chemotherapy compounds within tumor tissue is one of the main challenges in the development of antineoplastic drugs, and techniques for simple, inexpensive, sensitive, and selective detection of various analytes in tumors are of great importance. In this paper we propose the use of platinized carbon nanoelectrodes (PtNEs) for the electrochemical detection of platinum-based drugs in various biological models, including single cells and tumor spheroids in vitro and inside solid tumors in vivo. We have demonstrated the quantitative direct detection of Pt(II) in breast adenocarcinoma MCF-7 cells treated with cisplatin and a cisplatin-based DNP prodrug. To realize the potential of this technique in advanced tumor models, we measured Pt(II) in 3D tumor spheroids in vitro and in tumor-bearing mice in vivo. The concentration gradient of Pt(II) species correlated with the distance from the sample surface in MCF-7 tumor spheroids. We then performed the detection of Pt(II) species in tumor-bearing mice treated intravenously with cisplatin and DNP. We found that there was deeper penetration of DNP in comparison to cisplatin. This research demonstrates a minimally invasive, real-time electrochemical technique for the study of platinum-based drugs.


Assuntos
Antineoplásicos , Pró-Fármacos , Animais , Cisplatino/química , Cisplatino/farmacologia , Humanos , Células MCF-7 , Camundongos , Pró-Fármacos/química , Distribuição Tecidual
16.
J Food Sci ; 87(4): 1540-1551, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35279843

RESUMO

The physicochemical, structural, and functional properties of albumin, globulin, glutelin, and protein isolate (JSPI) extracted from jackfruit seeds were investigated. Protein fractions and JSPI were rich in amino acids, which can be comparable to soy protein. Other essential amino acids except histidine met the FAO/WHO/UNO-recommended intake for infants and adults. Jackfruit seed proteins were mainly composed of 17-26 kDa polypeptides, ß-sheet, and random coil were the main secondary structures. Glutelin (572.55) and JSPI (246.14) have higher H0 under neutral conditions, consistent with the solubility and emulsification properties results. Albumin and globulin had good solubility and were mostly soluble under neutral or weak alkaline conditions. In general, protein fractions and JSPI exhibited good foaming and emulsification properties. Therefore, jackfruit seed proteins have the potential to be nutritious functional ingredients in the food industry. PRACTICAL APPLICATION: Jackfruit seed proteins had high essential amino acids content and good functional properties. They can be used as a new type of functional ingredients in the food industry, which can not only reduce the environment pollution of discarded seeds but also improve use of plant protein.


Assuntos
Artocarpus , Globulinas , Adulto , Albuminas , Aminoácidos Essenciais/análise , Artocarpus/química , Globulinas/química , Glutens/química , Humanos , Proteínas de Plantas/química , Sementes/química , Solubilidade
17.
J Clin Lab Anal ; 36(5): e24361, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35318719

RESUMO

BACKGROUND: Recent studies showed that inflammation and immunity might play essential roles in the progression of intracerebral hemorrhage (ICH). However, the underlying mechanisms for changes at the cellular and molecular levels after ICH remain unclear. METHODS: We downloaded the microarray dataset of ICH from the Gene Expression Omnibus (GEO) database. The differential expression gene analysis was obtained by weighted gene co-expression network analysis (WGCNA). We got the hub genes and performed the biological functions and signaling pathways of these genes by Metascape. GSVA algorithm was used to evaluate the potential physical function of time-varying ICH samples. We used single-sample gene set enrichment analysis (ssGSEA) to assess the immune signatures infiltration and analyzed the correlation between hub genes and immune signatures. RESULTS: The data sets of all 22 ICH samples in GSE125512 were examined by the WGCNA R package. We finally screened five hub genes (GAPDH, PF4, SELP, APP, and PPBP) in the royal blue module. Metascape analysis displayed the biological processes related to inflammation and immunology. Cell adhesion molecule binding, myeloid leukocyte activation, CXCR chemokine receptor binding, and regulation of cytokine production were the most enriched pathophysiological process. The immune signatures infiltration analyses showed that ICH patients' early and late samples had different activity and abundance of immune-related cells and types. CONCLUSIONS: GAPDH, PF4, SELP, APP, and PPBP are identified as potential biomarkers for predicting the progression of ICH. This study may help us better understand the immunologic mechanism and shed new light on the promising approaches of immunotherapy for ICH patients.

18.
Nucleic Acids Res ; 50(4): 2005-2018, 2022 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-35137179

RESUMO

The second cell fate decision in the early stage of mammalian embryonic development is pivotal; however, the underlying molecular mechanism is largely unexplored. Here, we report that Prmt1 acts as an important regulator in primitive endoderm (PrE) formation. First, Prmt1 depletion promotes PrE gene expression in mouse embryonic stem cells (ESCs). Single-cell RNA sequencing and flow cytometry assays demonstrated that Prmt1 depletion in mESCs contributes to an emerging cluster, where PrE genes are upregulated significantly. Furthermore, the efficiency of extraembryonic endoderm stem cell induction increased in Prmt1-depleted ESCs. Second, the pluripotency factor Klf4 methylated at Arg396 by Prmt1 is required for recruitment of the repressive mSin3a/HDAC complex to silence PrE genes. Most importantly, an embryonic chimeric assay showed that Prmt1 inhibition and mutated Klf4 at Arg 396 induce the integration of mouse ESCs into the PrE lineage. Therefore, we reveal a regulatory mechanism for cell fate decisions centered on Prmt1-mediated Klf4 methylation.


Assuntos
Embrião de Mamíferos/metabolismo , Endoderma , Proteína-Arginina N-Metiltransferases/metabolismo , Animais , Diferenciação Celular , Desenvolvimento Embrionário , Endoderma/metabolismo , Feminino , Camundongos , Células-Tronco Embrionárias Murinas , Gravidez
19.
Nanomaterials (Basel) ; 12(4)2022 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-35214950

RESUMO

Currently, there are several thermoelectric materials, such as Ag2Te, Bi2Te3, and Sb2Te3, that have been investigated for thermoelectric applications. However, the toxicity and rarity of most of these materials make them unsuitable for practical applications. In contrast, silver selenide (Ag2Se) is an abundant and environment-friendly thermoelectric material. This study provides a facile synthetic approach for preparing high-performance, low-cost, and flexible Ag2Se thermoelectric films. Ag2Se nanomaterials were prepared based on the chemical template method, and the reaction solution concentration was varied to systematically investigate the effects of reaction solution concentration on the characterization and thermoelectric properties of Ag2Se nanomaterials. For convenience of testing, the flexible Ag2Se films were prepared on porous nylon membranes using vacuum-assisted filtration. The prepared thermoelectric films were tested using an X-ray diffractometer, scanning electron microscope, Seebeck coefficient tester, and Hall tester. The film prepared from the solution with the lowest concentration (18.0 mM) demonstrated the best thermoelectric performance, with a maximum power factor of 382.18 µW∙m-1∙K-2 at ~400 K. Additionally, a cold-pressing treatment could effectively enhance the electrical conductivity of the film, without damaging the substrate, as the conductivity of the film remained at 90% of the original value after 1500 bending cycles.

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