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1.
Plant Physiol ; 2024 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-39471326

RESUMO

Regulation of responses induced by herbivory and jasmonic acid (JA) remains poorly understood in the important staple crop maize (Zea mays). MYC2 is the key transcription factor regulating many aspects of JA signaling, while mitogen-activated protein kinases (MAPKs or MPKs) play important roles in various plant physiological processes. Using a combination of reverse genetics, transcriptome analysis, and biochemical assays, we elucidated the important role of MPK4 in maize resistance to insects and in JA signaling. Silencing MPK4 increased the JA and jasmonoyl-isoleucine levels elicited by wounding or simulated herbivory but decreased maize resistance to armyworm (Mythimna separata) larvae. We showed that MPK4 is required for transcriptional regulation of many genes responsive to methyl jasmonate, indicating the important role of maize MPK4 in JA signaling. Biochemical analyses indicated that MPK4 directly phosphorylates MYC2s at Thr115 of MYC2a and Thr112 of MYC2b. Compared with nonphosphorylated MYC2s, phosphorylated MYC2s were more prone to degradation and exhibited enhanced transactivation activity against the promoters of several benzoxazinoid biosynthesis genes, which are important for maize defense against insects. This study reveals the essential role of maize MPK4 in JA signaling and provides insights into the functions of MAPKs in maize.

2.
Small ; 20(8): e2305374, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37724002

RESUMO

Hypertrophic scar (HS) is a common fibroproliferative disease caused by abnormal wound healing after deep skin injury. However, the existing approaches have unsatisfactory therapeutic effects, which promote the exploration of newer and more effective strategies. MiRNA-modified functional exosomes delivered by dissolvable microneedle arrays (DMNAs) are expected to provide new hope for HS treatment. In this study, a miRNA, miR-141-3p, which is downregulated in skin scar tissues and in hypertrophic scar fibroblasts (HSFs), is identified. MiR-141-3p mimics inhibit the proliferation, migration, and myofibroblast transdifferentiation of HSFs in vitro by targeting TGF-ß2 to suppress the TGF-ß2/Smad pathway. Subsequently, the engineered exosomes encapsulating miR-141-3p (miR-141-3pOE -Exos) are isolated from adipose-derived mesenchymal stem cells transfected with Lv-miR-141-3p. MiR-141-3pOE -Exos show the same inhibitive effects as miR-141-3p mimics on the pathological behaviors of HSFs in vitro. The DMNAs for sustained release of miR-141-3pOE -Exos are further fabricated in vivo. MiR-141OE -Exos@DMNAs effectively decrease the thickness of HS and improve fibroblast distribution and collagen fiber arrangement, and downregulate the expression of α-SMA, COL-1, FN, TGF-ß2, and p-Smad2/3 in the HS tissue. Overall, a promising, effective, and convenient exosome@DMNA-based miRNA delivery strategy for HS treatment is provided.


Assuntos
Cicatriz Hipertrófica , Exossomos , MicroRNAs , Humanos , Cicatriz Hipertrófica/terapia , Cicatriz Hipertrófica/genética , Cicatriz Hipertrófica/metabolismo , Fator de Crescimento Transformador beta2/metabolismo , Exossomos/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Fibroblastos/metabolismo , Proliferação de Células/genética
3.
J Transl Med ; 22(1): 451, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38741136

RESUMO

BACKGROUND: Facioscapulohumeral muscular dystrophy (FSHD) is a high-prevalence autosomal dominant neuromuscular disease characterized by significant clinical and genetic heterogeneity. Genetic diagnosis of FSHD remains a challenge because it cannot be detected by standard sequencing methods and requires a complex diagnosis workflow. METHODS: We developed a comprehensive genetic FSHD detection method based on Oxford Nanopore Technologies (ONT) whole-genome sequencing. Using a case-control design, we applied this procedure to 29 samples and compared the results with those from optical genome mapping (OGM), bisulfite sequencing (BSS), and whole-exome sequencing (WES). RESULTS: Using our ONT-based method, we identified 59 haplotypes (35 4qA and 24 4qB) among the 29 samples (including a mosaic sample), as well as the number of D4Z4 repeat units (RUs). The pathogenetic D4Z4 RU contraction identified by our ONT-based method showed 100% concordance with OGM results. The methylation levels of the most distal D4Z4 RU and the double homeobox 4 gene (DUX4) detected by ONT sequencing are highly consistent with the BSS results and showed excellent diagnostic efficiency. Additionally, our ONT-based method provided an independent methylation profile analysis of two permissive 4qA alleles, reflecting a more accurate scenario than traditional BSS. The ONT-based method detected 17 variations in three FSHD2-related genes from nine samples, showing 100% concordance with WES. CONCLUSIONS: Our ONT-based FSHD detection method is a comprehensive method for identifying pathogenetic D4Z4 RU contractions, methylation level alterations, allele-specific methylation of two 4qA haplotypes, and variations in FSHD2-related genes, which will all greatly improve genetic testing for FSHD.


Assuntos
Metilação de DNA , Distrofia Muscular Facioescapuloumeral , Sequenciamento Completo do Genoma , Distrofia Muscular Facioescapuloumeral/genética , Distrofia Muscular Facioescapuloumeral/diagnóstico , Humanos , Metilação de DNA/genética , Haplótipos/genética , Masculino , Estudos de Casos e Controles , Proteínas de Homeodomínio/genética , Feminino , Sequenciamento por Nanoporos/métodos , Adulto
4.
Analyst ; 149(6): 1907-1920, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38372525

RESUMO

Arachidonic acid metabolites are a family of bioactive lipids derived from membrane phospholipids. They are involved in cancer progression, but arachidonic acid metabolite profiles and their related biosynthetic pathways remain uncertain in colorectal cancer (CRC). To compare the arachidonic acid metabolite profiles between CRC patients and healthy controls, quantification was performed using a liquid chromatography-mass spectrometry-based analysis of serum and tissue samples. Metabolomics analysis delineated the distinct oxidized lipids in CRC patients and healthy controls. Prostaglandin (PGE2)-derived metabolites were increased, suggesting that the PGE2 biosynthetic pathway was upregulated in CRC. The qRT-PCR and immunohistochemistry analyses showed that the expression level of PGE2 synthases, the key protein of PGE2 biosynthesis, was upregulated in CRC and positively correlated with the CD68+ macrophage density and CRC development. Our study indicates that the PGE2 biosynthetic pathway is associated with macrophage infiltration and progression of CRC tumors.


Assuntos
Neoplasias Colorretais , Dinoprostona , Humanos , Dinoprostona/metabolismo , Ácido Araquidônico , Metaboloma , Metabolômica , Neoplasias Colorretais/metabolismo
5.
J Asian Nat Prod Res ; 26(10): 1192-1206, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38794953

RESUMO

Propolis is a natural resinous compound produced by bees, mixed with their saliva and wax, and has a range of biological benefits, including antioxidant and anti-inflammatory effects. This article reviews the in vivo transformation of propolis flavonoids and their potential influence on drug efficacy. Despite propolis is widely used, there is little research on how the active ingredients of propolis change in the body and how they interact with drugs. Future research will focus on these interactions and the metabolic fate of propolis in vivo.


Assuntos
Biotransformação , Flavonoides , Própole , Própole/química , Flavonoides/química , Flavonoides/farmacologia , Estrutura Molecular , Animais , Antioxidantes/farmacologia , Antioxidantes/química , Humanos , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Abelhas
6.
Cancer Sci ; 114(1): 63-74, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35524544

RESUMO

FAT atypical cadherin 1 (FAT1) is a mutant gene frequently found in human cancers and mainly accumulates at the plasma membrane of cancer cells. Emerging evidence has implicated FAT1 in the progression of gastric cancer (GC). This study intended to identify a regulatory network related to FAT1 in GC development. Upregulated expression of FAT1 was confirmed in GC tissues, and silencing FAT1 was observed to result in suppression of GC cell oncogenic phenotypes. Mechanistic investigation results demonstrated that FAT1 upregulated AP-1 expression by phosphorylating c-JUN and c-FOS, whereas LINC00857 elevated the expression of FAT1 by recruiting a transcription factor TFAP2C. Functional experiments further suggested that LINC00857 enhanced the malignant biological characteristics of GC cells through TFAP2C-mediated promotion of FAT1. More importantly, LINC00857 silencing delayed the tumor growth and blocked epithelial-mesenchymal transition in tumor-bearing mice, which was associated with downregulated expression of TFAP2C/FAT1. To conclude, LINC00857 plays an oncogenic role in GC through regulating the TFAP2C/FAT1/AP-1 axis. Therefore, this study contributes to extended the understanding of gastric carcinogenesis and LINC00857 may serve as a therapeutic target for GC.


Assuntos
Neoplasias Gástricas , Humanos , Animais , Camundongos , Neoplasias Gástricas/genética , Fator de Transcrição AP-1/genética , Linhagem Celular Tumoral , Carcinogênese/patologia , Regulação Neoplásica da Expressão Gênica , Proliferação de Células/genética , Transição Epitelial-Mesenquimal/genética , Movimento Celular , Caderinas/genética , Caderinas/metabolismo , Fator de Transcrição AP-2/genética
7.
Mol Cell Biochem ; 478(9): 2013-2027, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36598615

RESUMO

This work was aimed to investigate the action mechanism of berberine (BBR) on gluconeogenesis. The effects of BBR were examined in rat primary hepatocytes and confirmed in vivo in spontaneous diabetic rats. Protein levels were assessed by Western blot. Immunofluorescence staining was utilized for visualizing protein expression, while qRT-PCR helped for the determination of gene expression at the mRNA level. Besides, cGMP concentration was measured using ELISA, whereas NO level was assessed by spectrophotometry. BBR inhibited gluconeogenesis by downregulating G6Pase and PEPCK via inhibition of CREB phosphorylation. Moreover, BBR enhanced NO and cGMP concentrations, leading to the activation of the NO/cGMP/PKG signaling via activating AKT1/MAPK axis. The in vivo experiments were consistent with the findings obtained in vitro. Hence, BBR represents a drug candidate for diabetic patients and its mechanism of action may be driven via the AKT/MAPK/NO/cGMP/PKG pathway.


Assuntos
Berberina , Diabetes Mellitus Experimental , Ratos , Animais , Gluconeogênese , Proteínas Proto-Oncogênicas c-akt/metabolismo , Berberina/farmacologia , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Transdução de Sinais , GMP Cíclico/metabolismo
8.
Am J Obstet Gynecol ; 229(3): 302.e1-302.e18, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-36907537

RESUMO

BACKGROUND: Emerging studies suggest that whole genome sequencing provides additional diagnostic yield of genomic variants when compared with chromosomal microarray analysis in the etiologic diagnosis of infants and children with suspected genetic diseases. However, the application and evaluation of whole genome sequencing in prenatal diagnosis remain limited. OBJECTIVE: This study aimed to evaluate the accuracy, efficacy, and incremental yield of whole genome sequencing in comparison with chromosomal microarray analysis for routine prenatal diagnosis. STUDY DESIGN: In this prospective study, a total of 185 unselected singleton fetuses with ultrasound-detected structural anomalies were enrolled. In parallel, each sample was subjected to whole genome sequencing and chromosomal microarray analysis. Aneuploidies and copy number variations were detected and analyzed in a blinded fashion. Single nucleotide variations and insertions and deletions were confirmed by Sanger sequencing, and trinucleotide repeats expansion variants were verified using polymerase chain reaction plus fragment-length analysis. RESULTS: Overall, genetic diagnoses using whole genome sequencing were obtained for 28 (15.1%) cases. Whole genome sequencing not only detected all these aneuploidies and copy number variations in the 20 (10.8%) diagnosed cases identified by chromosomal microarray analysis, but also detected 1 case with an exonic deletion of COL4A2 and 7 (3.8%) cases with single nucleotide variations or insertions and deletions. In addition, 3 incidental findings were detected including an expansion of the trinucleotide repeat in ATXN3, a splice-sites variant in ATRX, and an ANXA11 missense mutation in a case of trisomy 21. CONCLUSION: Compared with chromosomal microarray analysis, whole genome sequencing increased the additional detection rate by 5.9% (11/185). Using whole genome sequencing, we detected not only aneuploidies and copy number variations, but also single nucleotide variations and insertions and deletions, trinucleotide repeat expansions, and exonic copy number variations with high accuracy in an acceptable turnaround time (3-4 weeks). Our results suggest that whole genome sequencing has the potential to be a new promising prenatal diagnostic test for fetal structural anomalies.


Assuntos
Variações do Número de Cópias de DNA , Ultrassonografia Pré-Natal , Gravidez , Feminino , Lactente , Criança , Humanos , Estudos Prospectivos , Primeiro Trimestre da Gravidez , Diagnóstico Pré-Natal/métodos , Aneuploidia , Sequenciamento Completo do Genoma , Análise em Microsséries , Aberrações Cromossômicas
9.
Fish Shellfish Immunol ; 136: 108700, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36966895

RESUMO

In recent years, the widespread use of antibiotics in intensive grouper mariculture has resulted in the ineffectiveness of antibiotic treatment, leading to an increasing incidence of diseases caused by bacteria, viruses, and parasites, causing serious economic losses. Hence, it is crucial to develop alternative strategies to antibiotics for healthy and sustainable development of the mariculture industry. Here, we aimed to screen host gut-derived probiotics and evaluate its effects on growth and immunity of grouper. In this study, 43 bacterial strains were isolated from the intestine of the hybrid grouper (Epinephelus fuscoguttatus♀ × E. lanceolatus♂), and a potential probiotic strain G1-26, which can efficiently secrete amylase, protease, and lipase, was obtained using different screening mediums. Based on 16S rDNA sequencing, the potential probiotic strain G1-26 was identified as Vibrio fluvialis. The results of a biological characteristic evaluation showed that V. fluvialis G1-26 could grow at 25-45 °C, pH 5.5-7.5, salinity 10-40, and bile salt concentration 0-0.030%, and produce amylase, lipase, and protease under different culture conditions. Additionally, V. fluvialis G1-26 is sensitive to many antibiotics and does not exhibit aquatic biotoxicity. Subsequently, hybrid groupers were fed diets containing V. fluvialis G1-26 at different concentrations (0, 106, 108, and 1010 CFU/g) for 60 d. The results showed that V. fluvialis G1-26 at 108 CFU/g did not significantly affect the growth performance of the hybrid grouper (P > 0.05). V. fluvialis G1-26 supplementation at 108 and 1010 CFU/g significantly promoted the relative expression of immune-related genes in hybrid groupers (TLR3, TLR5, IL-1ß, IL-8, IL-10, CTL, LysC, TNF-2, and MHC-2) and improved the activities of alkaline phosphatase, acid phosphatase, total superoxide dismutase, and total protein in the liver. In conclusion, V. fluvialis G1-26, a potential probiotic strain isolated from the intestine of the hybrid grouper, can be used as an effective immunopotentiator at an optimal dose of 108 CFU/g diet. Our results provide a scientific basis for the development and utilization of probiotics in the grouper mariculture industry.


Assuntos
Bass , Probióticos , Animais , Antioxidantes/metabolismo , Dieta/veterinária , Probióticos/farmacologia , Peptídeo Hidrolases , Amilases , Lipase , Ração Animal/análise
10.
Antonie Van Leeuwenhoek ; 116(12): 1395-1406, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37847452

RESUMO

Pseudomonas aeruginosa is one of the top-listed pathogens in nosocomial infection. It is notorious for its complicated virulence system and rapid adaptability to drugs or antimicrobials. In this study, we aimed to evaluate the prevalence of sixteen virulence genes in four groups including type III secretion system, biofilm formation, extracellular toxin biosynthesis and enzymes amongst 209 clinical Pseudomonas aeruginosa strains. We investigated the different distribution patterns of virulence genotypes based on carbapenem-resistant phenotype or the carriage of carbapenemase genes. The detection rate of each virulence gene varied greatly. phzM and plcN were detected in all collected strains, while pilB and exoU were only carried by a small portion of isolates (6.7% and 16.3%). Additionally, the number of genotypes observed in each group of examined virulence genes ranged from 4 to 8. Only the distribution of genotypes of type III secretion system showed statistical difference between carbapenem-mediated or carbapenem-resistant and carbapenem-sensitive strains. The virulence genotype of Pseudomonas aeruginosa was possibly interrelated to its resistance mechanism. Further research suggested that one particular TTSS genotype exhibited higher ratio in carbapenemase-producing strains and exoS was less frequently detected in CRPA strains carrying carbapenemase gene. Generally, the significant genetic diversity of virulence genes amongst Pseudomonas aeruginosa strains was highlighted in this study. Specific TTSS genotypes were associated with carbapenem-resistance. In particular, certain incompatibility might exist between exoS and carbapenemase genes, which provided valuable information for further understanding the relationship between carbapenem resistance and virulence.


Assuntos
Antibacterianos , Infecções por Pseudomonas , Humanos , Virulência/genética , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Pseudomonas aeruginosa/genética , Sistemas de Secreção Tipo III/genética , Centros de Atenção Terciária , Prevalência , Carbapenêmicos/farmacologia , Proteínas de Bactérias/genética , beta-Lactamases/genética , Testes de Sensibilidade Microbiana
11.
Neurol Sci ; 44(5): 1769-1772, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36809423

RESUMO

The GGC repeat expansions in the NOTCH2NLC gene are associated with multiple neurodegenerative disorders. Herein, we report the clinical phenotype in a family with biallelic GGC expansions in NOTCH2NLC. Autonomic dysfunction was a prominent clinical manifestation in three genetically confirmed patients without dementia, parkinsonism, and cerebellar ataxia for > 12 years. A 7-T brain magnetic resonance imaging in two patients revealed a change in the small cerebral veins. The biallelic GGC repeat expansions may not modify the disease progression in neuronal intranuclear inclusion disease. Autonomic dysfunction-dominant may expand the clinical phenotype of NOTCH2NLC.


Assuntos
Doenças do Sistema Nervoso Autônomo , Proteínas do Tecido Nervoso , Doenças Neurodegenerativas , Expansão das Repetições de Trinucleotídeos , Humanos , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , População do Leste Asiático , Corpos de Inclusão Intranuclear/patologia , Doenças Neurodegenerativas/genética , Fenótipo , Proteínas do Tecido Nervoso/genética , Peptídeos e Proteínas de Sinalização Intercelular/genética
12.
Biochem Genet ; 2023 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-37962692

RESUMO

Congenital contractural arachnodactyly (CCA) is a rare connective tissue disorder characterized by arachnodactyly, multiple joint contractures, progressive kyphoscoliosis, pectus deformity and abnormal crumpled ears. FBN2 is the only gene currently known to be associated with CCA. In this study, we report on a prenatal case presented with skeletal, cardiac and spinal malformations. And his father had elongated limbs, contractures of the proximal interphalangeal joints, high myopia and scoliosis. We conducted whole exome sequencing (WES) on the fetus-parental trio and a heterozygous variant (hg19 chr5:127,673,685, c.3598 + 4A > G, NM_001999.4) in intron 27 of the FBN2 gene was successfully identified, inherited from the father. Reverse transcriptase-polymerase chain reaction (RT-PCR) was performed to evaluate the potential splicing effect of this variant, which confirmed that the variant caused a deletion of exon 27 (126 bp) by disrupting the splice-donor site and destroyed the 17th calcium-binding epidermal growth factor-like (cbEGF) domain. Our research not only finds the etiology of the disease in affected individuals and expands the mutation spectrum of FBN2 gene, but also provides genetic counseling and fertility guidance for this family.

13.
Ultrastruct Pathol ; 47(6): 529-539, 2023 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-37953603

RESUMO

Medulloblastoma (MB) is a frequently occurring malignant brain tumor in children, and many of these tumors are identified by the abnormal activation of the Sonic Hedgehog (SHH) pathway. Although the Shh inhibitor GDC0449 initially shows some effectiveness in certain tumors, they eventually recur due to drug resistance mechanisms, highlighting the need for new treatment options. In this study, we explore whether GDC0449 induces autophagy in the human MB cell lines. To investigate the ultrastructural pathology changes of GDC0449-treated Daoy and D283 cells, we employed Transmission Electron Microscopy (TEM) technology to identify the expression of autophagic vacuoles. Our results indicate that GDC0449 only increases autophagy in Daoy cells by increasing the LC3-II/LC3-I ratio and autophagosome formation.We also analyzed Beclin1, LC3, Bax, and Cleaved-caspase3 protein and mRNA expression levels of autophagic and apoptotic markers using fluorescence confocal microscopy, RT-PCR, and Western blot. We found that cell autophagy and apoptosis increased in a dose-dependent manner with GDC0449 treatment. Additionally, we observed increased mammalian target of rapamycin (mTOR) phosphorylation and decreased protein kinase B (AKT/PKB), Ribosomal Protein S6, eIF4E-binding protein (4EBP1) phosphorylation in GDC0449-treated Daoy cells. It was observed that inhibiting autophagy using Beclin1 siRNA significantly blocked the apoptosis-inducing effects of GDC0449, suggesting that GDC0449 mediates its apoptotic effects by inducing autophagy.Our data suggests that GDC0449 inhibits the growth of human MB Daoy cells by autophagy-mediated apoptosis. The mechanism of GDC0449-induced autophagy in Daoy cells may be related to the inhibition of the PI3K/AKT/mTOR signaling pathway.


Assuntos
Neoplasias Cerebelares , Meduloblastoma , Criança , Humanos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-akt/farmacologia , Proteínas Hedgehog/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Fosfatidilinositol 3-Quinases/farmacologia , Proteína Beclina-1/farmacologia , Meduloblastoma/tratamento farmacológico , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Serina-Treonina Quinases TOR/farmacologia , Apoptose , Autofagia , Neoplasias Cerebelares/tratamento farmacológico , Linhagem Celular Tumoral
14.
Chem Biodivers ; 20(2): e202201060, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36579401

RESUMO

Fatty acid biosynthesis is essential for bacterial survival. Of these promising targets, ß-ketoacyl-acyl carrier protein (ACP) synthase III (FabH) is the most attractive target. A series of novel 1,3,4-oxadiazole-2(3H)-thione derivatives containing 1,4-benzodioxane skeleton targeting FabH were designed and synthesized. These compounds were determined by 1 H-NMR, 13 C-NMR, MS and further confirmed by crystallographic diffraction study for compound 7m and 7n. Most of the compounds exhibited good inhibitory activity against bacteria by computer-assisted screening, antibacterial activity test and E. coli FabH inhibitory activity test, wherein compounds 7e and 7q exhibited the most significant inhibitory activities. Besides, compound 7q showed the best E. coli FabH inhibitory activity (IC50 =2.45 µΜ). Computational docking studies also showed that compound 7q interacts with FabH critical residues in the active site.


Assuntos
3-Oxoacil-(Proteína de Transporte de Acila) Sintase , Proteínas de Escherichia coli , 3-Oxoacil-(Proteína de Transporte de Acila) Sintase/metabolismo , Antibacterianos/farmacologia , Bactérias , Inibidores Enzimáticos/química , Escherichia coli/metabolismo , Simulação de Acoplamento Molecular , Esqueleto/metabolismo , Tionas
15.
J Pak Med Assoc ; 73(6): 1175-1178, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37427610

RESUMO

OBJECTIVE: To investigate the effect of hybrid blood purification treatment on levels of serum molecular toxins, micro-inflammatory mediators and quality of life in maintenance haemodialysis patients. Methods: The analytical study was conducted at the Fifth Affiliated Hospital of Xinjiang Medical University, China, from January 2019 to January 2021, and adult maintenance haemodialysis patients of either gender who were having dialysis at least 3 times per week for at least 4 h each time. The patients were randomised into two equal groups. Group A received pure haemodialysis, while Group B was given hybrid blood purification treatment. Serum parathyroid hormone, Beta 2 microglobulin, high-sensitivity C-reactive protein and interleukin-6 were determined. Kidney disease target areas and short-form 36 scores were compared between the groups. All parameters were assessed at baseline and after 3 months of intervention. Data was analysed using SPSS 25. RESULTS: Of the 216 patients, 108(50%) were in each of the two groups. Overall, there were 120(55.6%) male and 96(44.4%) female subjects; mean age was 58.50±6.73 years; and mean dialysis duration was 31.92±5.05 months. At baseline, none of the study parameters were significantly different between the groups (p>0.05). Post-intervention, all parameters were lower in Group B compared to Group A (p<0.05). CONCLUSIONS: Compared to haemodialysis alone, hybrid blood purification treatment. I was found to be more effective in removing molecular toxins from haemodialysis patients' blood, reducing serum micro-inflammatory status, and improving their quality of life.


Assuntos
Nefropatias , Falência Renal Crônica , Adulto , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Qualidade de Vida , Diálise Renal/efeitos adversos , Nefropatias/etiologia , Proteína C-Reativa , China , Falência Renal Crônica/terapia , Falência Renal Crônica/etiologia
16.
Biochem Biophys Res Commun ; 605: 39-44, 2022 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-35306363

RESUMO

Chronic social stress is closed related to major depressive disorder, torturing millions of people and may destroy their lives. The prefrontal cortex is one of the core brain areas involved in pathological development and behavior changes in depression. CELF4 is a neuronal RNA-binding protein and plays an essential role in RNA processing. It is closely related to some neurological disorders, including seizures and neuroticism. Most recently, GWAS analysis indicates it is one of the significant genes associated with depression. Nonetheless, we are still unknown whether and how CELF4 gets involved in depression. Here, we reported that the protein and mRNA expression levels of CELF4 in the PFC were decreased in the CSDS depression model, as well as the spine number. Furthermore, we disturbed CELF4 expression in the PFC by using the AAV-shCELF4 virus. Unexpectedly, the spine number showed a decrease in PFC because of the impaired CELF4 expression, and the AAV-shCELF4 mice displayed depression-like behaviors. Our results suggest that CELF4 is critical for spine number and acts a critical role in depression-like behaviors of mice.


Assuntos
Depressão , Transtorno Depressivo Maior , Animais , Proteínas CELF/metabolismo , Depressão/genética , Transtorno Depressivo Maior/genética , Transtorno Depressivo Maior/metabolismo , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/metabolismo , Córtex Pré-Frontal/metabolismo , Estresse Psicológico/genética , Estresse Psicológico/metabolismo
17.
Small ; 18(12): e2105890, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35072345

RESUMO

This work reports a molecular-scale capacitance effect of the double helical nucleic acid duplex structure for the first time. By quantitatively conducting large sample measurements of the electrostatic field effect using a type of high-accuracy graphene transistor biosensor, an unusual charge-transport behavior is observed in which the end-immobilized nucleic acid duplexes can store a part of ionization electrons like molecular capacitors, other than electric conductors. To elucidate this discovery, a cascaded capacitive network model is proposed as a novel equivalent circuit of nucleic acid duplexes, expanding the point-charge approximation model, by which the partial charge-transport observation is reasonably attributed to an electron-redistribution behavior within the capacitive network. Furthermore, it is experimentally confirmed that base-pair mismatches hinder the charge transport in double helical duplexes, and lead to directly identifiable alterations in electrostatic field effects. The bioelectronic principle of mismatch impact is also self-consistently explained by the newly proposed capacitive network model. The mesoscopic nucleic acid capacitance effect may enable a new kind of label-free nucleic acid analysis tool based on electronic transistor devices. The in situ and real-time nucleic acid detections for virus biomarkers, somatic mutations, and genome editing off-target may thus be predictable.


Assuntos
Técnicas Biossensoriais , Grafite , Ácidos Nucleicos , Capacitância Elétrica , Grafite/química , Transistores Eletrônicos
18.
Cytotherapy ; 24(3): 262-271, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34836820

RESUMO

BACKGROUND AIMS: Mesenchymal stromal cells (MSCs) remain an area of interest in the field of regenerative medicine. Although there is clear evidence of safety, a lack of substantial efficacy has led to many MSC-based clinical trials to stall in phase 1. Therefore, potentiating MSCs with biologically relevant messenger RNA (mRNA) transcripts presents a relatively safe and efficient way to increase functionality. METHODS: In this study, human bone marrow-derived MSCs were transfected with endothelial nitric oxide synthase (eNOS) mRNA and evaluated for transfection efficiency and immunosuppressive ability. To assess MSC-eNOS functionality, T-cell proliferation assays and mouse models of experimental autoimmune encephalomyelitis and graft-versus-host disease were used. RESULTS: The authors found that MSC-eNOS retained MSC characteristics and exhibited significantly enhanced immunosuppressive effects compared with naive MSCs in both in vitro and in vivo models. CONCLUSIONS: It is feasible to pursue eNOS mRNA transfection to potentiate the immunomodulatory capacity of MSCs for clinical applications in the future.


Assuntos
Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Animais , Camundongos , Óxido Nítrico Sintase Tipo III/genética , RNA Mensageiro/genética , Transfecção
19.
Horm Metab Res ; 54(6): 354-360, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35697044

RESUMO

Aim was to explore the associations between baseline cortisol levels and surgery method of primary bilateral macronodular adrenal hyperplasia (PBMAH). We retrospectively reviewed the clinical features and management of 30 patients (18 females and 12 males) who were diagnosed with PBMAH in our center between 2005 and 2019. Based on surgery method, we divided the patients into two groups: unilateral adrenalectomy (UA) group; and bilateral adrenalectomy (BA) group. Serum cortisol rhythm and 24-hour urinary free cortisol (UFC/24 h) levels were assayed using chemiluminescence method. Associations between baseline cortisol levels and BA were assessed using logistic regression. The predictive value of baseline cortisol levels for BA was calculated using receiver operating characteristic (ROC) curves. Twenty patients (66.7%) underwent UAs and ten patients (33.3%) underwent BAs. After adjusting for age, sex, BMI, SBP, and adrenal volume, the concentrations of baseline serum cortisol (8 AM, 4 PM, and 0 AM) and UFC/24 h were associated with bilateral adrenalectomy (all p<0.05). The area under the ROC curve based on 8 AM serum cortisol level model was larger than that in models based on 4 PM, 0 AM serum cortisol levels and UFC/24 h, but the differences were non-significant (all p>0.05). According to maximum Youden index criteria, the optimal cutoffs of 8 AM serum cortisol level and UFC were 26.89 µg/dl and 406.65 µg/24 h, respectively, for BA. The baseline cortisol levels are positively associated with BA. Increased levels of baseline cortisol levels may predict higher possibility of BA, which should be confirmed by prospective studies.


Assuntos
Adrenalectomia , Hidrocortisona , Feminino , Humanos , Hiperplasia , Masculino , Estudos Prospectivos , Estudos Retrospectivos
20.
Wound Repair Regen ; 30(2): 245-257, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34921570

RESUMO

The application of photobiomodulation (PBM) in regenerative medicine has expanded to the treatment of alopecia caused by various reasons. However, the mechanisms responsible for its effects are poorly understood. Here, we aimed to investigate the effects of PBM on hair regeneration in injured skin and to explore the underlying mechanisms. The scratched epidermis or dermis models were established in C57 mice aged 7-8 weeks. We found that the scratched epidermis had no influence on hair regeneration, but the scratched dermis led to obvious hair follicle atrophy and significantly influenced hair regeneration. The wounds in scratched dermis models were treated with PBM (655 nm, 3 J/cm2 [10 min]) and the hair regeneration and cell proliferation in hair follicle were evaluated. Compared with control, the hair coverage level was significantly enhanced after PBM treatment. Sox9+ and PCNA+ cells in hair follicle were obviously observed in PBM-treated group, but not in control. In vitro, the effects of PBM on the function of dermal papilla cells (DPCs) were investigated. The results showed that the migration of DPCs was increased significantly by PBM (655 nm, 3 J/cm2 [10 min]), whereas no effect was found on proliferation. Furthermore, we found that PBM promoted exosome secretion of DPCs, accompanied by the activation of Akt/GSK-3ß/ß-catenin pathway. AKT inhibitor MK-2206 effectively blocked PBM-induced migration and exosome secretion of DPCs. These findings suggest that the enhanced migration and exosome secretion of DPCs mediated by the Akt/GSK-3ß/ß-catenin pathway were responsible for the promotion of hair regeneration in injured skin by PBM.


Assuntos
Derme , beta Catenina , Animais , Proliferação de Células , Células Cultivadas , Glicogênio Sintase Quinase 3 beta/metabolismo , Cabelo/metabolismo , Folículo Piloso , Camundongos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Cicatrização , beta Catenina/metabolismo
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