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1.
Int J Mol Sci ; 25(9)2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38732136

RESUMO

In the context of sustainable agriculture and biomaterial development, understanding and enhancing plant secondary cell wall formation are crucial for improving crop fiber quality and biomass conversion efficiency. This is especially critical for economically important crops like upland cotton (Gossypium hirsutum L.), for which fiber quality and its processing properties are essential. Through comprehensive genome-wide screening and analysis of expression patterns, we identified a particularly high expression of an R2R3 MYB transcription factor, GhMYB52 Like, in the development of the secondary cell wall in cotton fiber cells. Utilizing gene-editing technology to generate a loss-of-function mutant to clarify the role of GhMYB52 Like, we revealed that GhMYB52 Like does not directly contribute to cellulose synthesis in cotton fibers but instead represses a subset of lignin biosynthesis genes, establishing it as a lignin biosynthesis inhibitor. Concurrently, a substantial decrease in the lint index, a critical measure of cotton yield, was noted in parallel with an elevation in lignin levels. This study not only deepens our understanding of the molecular mechanisms underlying cotton fiber development but also offers new perspectives for the molecular improvement of other economically important crops and the enhancement of biomass energy utilization.


Assuntos
Fibra de Algodão , Regulação da Expressão Gênica de Plantas , Gossypium , Lignina , Proteínas de Plantas , Lignina/biossíntese , Gossypium/genética , Gossypium/metabolismo , Gossypium/crescimento & desenvolvimento , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Parede Celular/metabolismo , Parede Celular/genética , Celulose/biossíntese , Celulose/metabolismo , Vias Biossintéticas
3.
Mol Ecol ; : e17385, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38738821

RESUMO

Microbes are thought to be distributed and circulated around the world, but the connection between marine and terrestrial microbiomes remains largely unknown. We use Plantibacter, a representative genus associated with plants, as our research model to investigate the global distribution and adaptation of plant-related bacteria in plant-free environments, particularly in the remote Southern Ocean and the deep Atlantic Ocean. The marine isolates and their plant-associated relatives shared over 98% whole-genome average nucleotide identity (ANI), indicating recent divergence and ongoing speciation from plant-related niches to marine environments. Comparative genomics revealed that the marine strains acquired new genes via horizontal gene transfer from non-Plantibacter species and refined existing genes through positive selection to improve adaptation to new habitats. Meanwhile, marine strains retained the ability to interact with plants, such as modifying root system architecture and promoting germination. Furthermore, Plantibacter species were found to be widely distributed in marine environments, revealing an unrecognized phenomenon that plant-associated microbiomes have colonized the ocean, which could serve as a reservoir for plant growth-promoting microbes. This study demonstrates the presence of an active reservoir of terrestrial plant growth-promoting bacteria in remote marine systems and advances our understanding of the microbial connections between plant-associated and plant-free environments at the genome level.

4.
Eur J Pharm Biopharm ; 199: 114299, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38643953

RESUMO

Lipid-polymer nanoparticles offer a promising strategy for improving gene nanomedicines by combining the benefits of biocompatibility and stability associated with the individual systems. However, research to date has focused on poly-lactic-co-glycolic acid (PLGA) and resulted in inefficient transfection. In this study, biocompatible Eudragit constructs E100 and RS100 were formulated as lipid-polymer nanoparticles loaded with pDNA expressing red fluorescent protein (RFP) as a model therapeutic. Using a facile nanoprecipitation technique, a core-shell structure stabilised by lipid-polyethylene glycol (PEG) surfactant was produced and displayed resistance to ultracentrifugation. Both cationic polymers E100 (pH-sensitive dissolution at 5) and RS100 (pH-insensitive dissolution) produced 150-200 nm sized particles with a small positive surface charge (+3-5 mV) and high pDNA encapsulation efficiencies (EE) of 75-90%. The dissolution properties of the Eudragit polymers significantly impacted the biological performance in human embryonic kidney cells (HEK293T). Nanoparticles composed of polymer RS100 resulted in consistently high cell viability (80-100%), whereas polymer E100 demonstrated dose-dependent behaviour (20-90% cell viability). The low dissolution of polymer RS100 over the full pH range and the resulting nanoparticles failed to induce RFP expression in HEK293T cells. In contrast, polymer E100-constructed nanoparticles resulted in reproducible and gradually increasing RFP expression of 26-42% at 48-72 h. Intraperitoneal (IP) injection of the polymer E100-based nanoparticles in C57BL/6 mice resulted in targeted RFP expression in mouse testes with favourable biocompatibility one-week post-administration. These findings predicate Eudragit based lipid-polymer nanoparticles as a novel and effective carrier for nucleic acids, which could facilitate pre-clinical evaluation and translation of gene nanomedicines.


Assuntos
DNA , Nanopartículas , Plasmídeos , Transfecção , Humanos , Animais , Nanopartículas/química , Concentração de Íons de Hidrogênio , Plasmídeos/administração & dosagem , Transfecção/métodos , Células HEK293 , Camundongos , DNA/administração & dosagem , DNA/química , Lipídeos/química , Polímeros/química , Solubilidade , Tamanho da Partícula , Polietilenoglicóis/química , Proteína Vermelha Fluorescente , Ácidos Polimetacrílicos/química , Masculino , Acrilatos
5.
Sci Rep ; 14(1): 8456, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38605053

RESUMO

Current low-light enhancement algorithms fail to suppress noise when enhancing brightness, and may introduces structural distortion and color distortion caused by halos or artifacts. This paper proposes a content-illumination coupling guided low-light image enhancement network (CICGNet), it develops a truss topology based on Retinex as backbone to decompose low-light image component in an end-to-end way. The preservation of content features and the enhancement of illumination features are carried out along with depth and width direction of the truss topology. Each submodule uses the same resolution input and output to avoid the introduction of noise. Illumination component prevents misestimation of global and local illumination by using pre- and post-activation features at different depth levels, this way could avoid possible halos and artifacts. The network progressively enhances the illumination component and maintains the content component stage-by-stage. The proposed algorithm demonstrates better performance compared with advanced attention-based low-light enhancement algorithms and state-of-the-art image restoration algorithms. We also perform extensive ablation studies and demonstrate the impact of low-light enhancement algorithm on the downstream task of computer vision. Code is available at: https://github.com/Ruini94/CICGNet .

6.
Front Oncol ; 14: 1344290, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38469234

RESUMO

Ferroptosis differs from traditional cell death mechanisms like apoptosis, necrosis, and autophagy, primarily due to its reliance on iron metabolism and the loss of glutathione peroxidase activity, leading to lipid peroxidation and cell death. The dysregulation of iron metabolism is a hallmark of various cancers, contributing to tumor progression, metastasis, and notably, drug resistance. The acquisition of mesenchymal characteristics by epithelial cells is known as Epithelial-Mesenchymal Transition (EMT), a biological process intricately linked to cancer development, promoting traits such as invasiveness, metastasis, and resistance to therapeutic interventions. EMT plays a pivotal role in cancer progression and contributes significantly to the complex dynamics of carcinogenesis. Research findings indicate that mesenchymal cancer cells exhibit greater susceptibility to ferroptosis compared to their epithelial counterparts. The induction of ferroptosis becomes more effective in eliminating drug-resistant cancer cells during the process of EMT. The interplay between ferroptosis and EMT, a process where epithelial cells transform into mobile mesenchymal cells, is crucial in understanding cancer progression. EMT is associated with increased cancer metastasis and drug resistance. The review delves into how ferroptosis and EMT influence each other, highlighting the role of key proteins like GPX4, which protects against lipid peroxidation, and its inhibition can induce ferroptosis. Conversely, increased GPX4 expression is linked to heightened resistance to ferroptosis in cancer cells. Moreover, the review discusses the implications of EMT-induced transcription factors such as Snail, Zeb1, and Twist in modulating the sensitivity of tumor cells to ferroptosis, thereby affecting drug resistance and cancer treatment outcomes. Targeting the ferroptosis pathway offers a promising therapeutic strategy, particularly for tumors resistant to conventional treatments. The induction of ferroptosis in these cells could potentially overcome drug resistance. However, translating these findings into clinical practice presents challenges, including understanding the precise mechanisms of ferroptosis induction, identifying predictive biomarkers, and optimizing combination therapies. The review underscores the need for further research to unravel the complex interactions between ferroptosis, EMT, and drug resistance in cancer. This could lead to the development of more effective, targeted cancer treatments, particularly for drug-resistant tumors, offering new hope in cancer therapeutics.

7.
BMC Pediatr ; 24(1): 178, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38481189

RESUMO

BACKGROUND: Amniotic fluid contamination (AFC) is a risk factor for neonatal hypoxic ischemic encephalopathy (HIE); however, the correlation between AFC level and the incidence and clinical grading of HIE, in addition to relevant biomarkers of brain damage, have not been assessed. METHODS: This single-center observational study included 75 neonates with moderate-to-severe HIE. The neonates with HIE were divided into four subgroups according to the AFC level: normal amniotic fluid with HIE group (NAF-HIE), I°AFC with HIE group (I°AFC-HIE), II°AFC with HIE group (II°AFC-HIE), and III°AFC with HIE group (III°AFC-HIE). The control groups consisted of 35 healthy neonates. The clinical grading of neonatal HIE was performed according to the criteria of Sarnat and Sarnat. Serum tau protein and S100B were detected by enzyme-linked immunosorbent assay kits. Correlations of serum tau protein and S100B were evaluated using the Pearson correlation analysis. RESULTS: (1) The incidence of neonatal HIE in the NAF-HIE group was 20 cases (26. 7%), I°AFC-HIE was 13 cases (17.3%), II°AFC-HIE was 10 cases (13.3%), and III°AFC-HIE was 32 cases (42. 7%). The incidence of moderate-to-severe HIE in the I°-III°AFC-HIE groups was 73.3% (55/75). (2) In 44 cases with severe HIE, 26 cases (59.1%) occurred in the III°AFC-HIE group, which had a significantly higher incidence of severe HIE than moderate HIE (p < 0.05). In NAF-HIE and I°AFC-HIE groups, the incidence of moderate HIE was 45.2% and 29.0%, respectively, which was higher than that of severe HIE (X2 = 9.2425, p < 0.05; X2 = 5.0472, p < 0.05, respectively). (3) Serum tau protein and S100B levels in the HIE groups were significantly higher than in the control group (all p < 0.05), and were significantly higher in the III°AFC-HIE group than in the NAF-HIE and I°AFC-HIE groups (all p < 0.05). (4) Serum tau protein and S100B levels in the severe HIE group were significantly higher in the moderate HIE group (all p < 0.05). (5) Serum tau protein and S100B levels were significantly positively correlated (r = 0.7703, p < 0.0001). CONCLUSION: Among children with severe HIE, the incidence of III°AFC was higher, and the levels of serum tau protein and S100B were increased. AFC level might be associated with HIE grading.


Assuntos
Lesões Encefálicas , Hipóxia-Isquemia Encefálica , Recém-Nascido , Criança , Humanos , Hipóxia-Isquemia Encefálica/etiologia , Proteínas tau , Líquido Amniótico , Biomarcadores , Encéfalo
9.
Artigo em Inglês | MEDLINE | ID: mdl-38347432

RESUMO

Microfluidics is widely regarded as a leading technology for industrial-scale manufacture of multicomponent, gene-based nanomedicines in a reproducible manner. Yet, very few investigations detail the impact of flow conditions on the biological performance of the product, particularly biocompatibility and therapeutic efficiency. Herein, this study investigated the engineering of a novel lipid-Eudragit hybrid nanoparticle in a bifurcating microfluidics micromixer for plasmid DNA (pDNA) delivery. Nanoparticles of ~150 nm in size, with uniform polydispersity index (PDI = 0.2) and ξ-potential of 5-11 mV were formed across flow rate ratios (FRR, aqueous to organic phase) of 3:1 and 5:1, respectively. The hybrid nanoparticles maintained colloidal stability and structural integrity of loaded pDNA following recovery by ultracentrifugation. Importantly, in vitro testing in human embryonic kidney cell line (HEK293T) revealed significant differences in biocompatibility and transfection efficiency (TE). Lipid-Eudragit nanoparticles produced at FRR 3:1 displayed high cellular toxicity (0-30% viability), compared with nanoparticles prepared at FRR 5:1 (50-100% viability). Red fluorescent protein (RFP) expression was sustained for 24-72 h following exposure of cells to nanoparticles, indicating controlled release of pDNA and trafficking to the nucleus. Nanoparticles produced at FRR 5:1 resulted in markedly higher TE (12%) compared with those prepared at FRR 3:1 (2%). Notably, nanoparticles produced using the bench-scale nanoprecipitation method resulted in lower biocompatibility (30-90%) but higher RFP expression (25-38%). These findings emphasize the need for in-depth analysis of the effect of formulation and flow conditions on the physicochemical and biological performance of gene nanomedicines when transitioning from bench to clinic.

10.
Placenta ; 146: 71-78, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38190772

RESUMO

The human placenta releases diverse extracellular vesicles (EVs), including microvesicles (100-1000 nm) and exosomes (30-150 nm), into the maternal blood for feto-maternal communication. Exosomes and microvesicles contribute to normal pregnancy physiology and major pregnancy pathologies. Differences in miRNA expressions and protein content in placental exosomes have been reported in complicated pregnancies. During human pregnancy, Corticotropin-Releasing Hormone (CRH) is produced and released by the placenta into the maternal blood. CRH is involved in regulating gestational length and the initiation of labour. CRH mRNA levels in the maternal plasma rise with gestation. High levels of CRH mRNA are reported to be associated with preeclamptic and preterm pregnancies. However, the underlying mechanism of placental CRH mRNA secretion remains to be elucidated. We hypothesise that the placenta releases CRH mRNA packaged within extracellular vesicles (EVs) into the maternal blood. In this study, placental EVs (microvesicles and exosomes) were isolated from human term healthy placentas via villus washes and from explant culture media by differential centrifugation and purified by density gradient ultracentrifugation using a continuous sucrose gradient (0.25-2.5 M). Western blotting using placenta- and exosome-specific markers and electron microscopy confirmed exosomes and microvesicles in the placental wash and explant media samples. Real-time quantitative RT-PCR data detected CRH mRNA in placenta-derived EVs from placental washes and explants. We also sorted placenta-secreted EVs in maternal plasma samples (≥37 weeks) by high-resolution flow cytometry using a fluorescent-labelled PLAP antibody. CRH mRNA was demonstrated in placental EVs obtained from maternal blood plasma. We therefore show that human placental EVs carry CRH mRNA into the maternal blood. Our study implies that measuring CRH mRNA in placental EVs in the maternal plasma could beused for monitoring pregnancy.


Assuntos
Hormônio Liberador da Corticotropina , Vesículas Extracelulares , Recém-Nascido , Gravidez , Humanos , Feminino , RNA Mensageiro/análise , Placenta/química , Vesículas Extracelulares/metabolismo , Hormônio Adrenocorticotrópico
11.
Proc Inst Mech Eng H ; 237(12): 1348-1365, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38031395

RESUMO

In this study, carboxylated carbon nanotube (CNT)-loaded curcumin (CUR) was blended into calcium phosphate cement (CPC) owing to the poor mechanical properties and single function of CPC as a bone-filling material, and CNT-CUR-CPC with improved strength and antitumor properties was obtained. The failure strength, hydrophilicity, in vitro bioactivity, bacteriostatic activity, antitumor activity, and cell safety of CNT-CUR-CPC were evaluated. The experimental results indicated that the failure strength of CNT-CUR-CPC increased from 25.05 to 45.05 MPa (p < 0.001) and its contact angle decreased from 20.37° to 15.27° (p < 0.001) after the CNT-CUR complex was added into CPC at the rate of 5 wt% and blended. Following soaking in simulated body fluid (m-SBF), the main components of CNT-CUR-CPC were hydroxyapatite (HA) and carbonate hydroxyapatite (HCA). The incorporation of CNT-CUR was beneficial for the deposition of PO43- and CO32-, and it promoted the crystallization of HA and HCA. For CNT-CUR-CPC, the inhibition zone diameter on Staphylococcus aureus was 10.2 ± 1.02 mm (p < 0.001) and it exhibited moderate sensitivity, whereas the inhibition zone diameter on Escherichia coli was 8.3 ± 0.23 mm (p < 0.001) and it exhibited low sensitivity. When compared with the CPC, the cell proliferation rate (RGR %) of the CNT-CUR-CPC decreased by 7.73% (p > 0.05) at 24 h, 17.89% (p < 0.05) at 48 h, and 24.43% (p < 0.001) at 72 h when MG63 cells were cultured on it. In particular, after the MG63 cells were cultured with the CNT-CUR-CPC for 48 h, the number of newly proliferating MG63 cells was significantly reduced, and their growth and adhesion on the surface of the CNT-CUR-CPC were inhibited when compared with the CPC. When 3T3-E1 cells were exposed to the m-SBF immersion solution of CNT-CUR-CPC, the cell proliferation rate (RGR %) was ≥80% (p > 0.05) and the cytotoxicity grade was 0-1. The 3T3-E1 cells were cultured with the m-SBF soaking solution of CNT-CUR-CPC for 24 h, and no significant changes in cell morphology or cytotoxicity were observed. After the 3T3-E1 cells were cultured on CNT-CUR-CPC for 48 h, they could stick to and grow on its surface without adverse reactions. CNT-CUR-CPC had a hemolysis rate of 4.3% (p > 0.05) and did not result in hemolysis and hemagglutination. The obtained CNT-CUR-CPC scaffold material exhibited effective antibacterial activity and cell safety, and could achieve a certain antitumor effect, which has a wide application potential in bone tissue engineering.


Assuntos
Curcumina , Nanotubos de Carbono , Humanos , Cimentos Ósseos/farmacologia , Cimentos Ósseos/química , Teste de Materiais , Curcumina/farmacologia , Hemólise , Força Compressiva , Fosfatos de Cálcio/química , Durapatita/farmacologia , Durapatita/química
13.
Nat Commun ; 14(1): 6487, 2023 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-37838746

RESUMO

Synthetic auxotrophy in which cell viability depends on the presence of an unnatural amino acid (unAA) provides a powerful strategy to restrict unwanted propagation of genetically modified organisms (GMOs) in open environments and potentially prevent industrial espionage. Here, we describe a generic approach for robust biocontainment of budding yeast dependent on unAA. By understanding escape mechanisms, we specifically optimize our strategies by introducing designed "immunity" to the generation of amber-suppressor tRNAs and developing the transcriptional- and translational-based biocontainment switch. We further develop a fitness-oriented screening method to easily obtain multiplex safeguard strains that exhibit robust growth and undetectable escape frequency (<~10-9) on solid media for 14 days. Finally, we show that employing our multiplex safeguard system could restrict the proliferation of strains of interest in a real fermentation scenario, highlighting the great potential of our yeast biocontainment strategy to protect the industrial proprietary strains.


Assuntos
Aminoácidos , Saccharomyces cerevisiae , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Aminoácidos/metabolismo , Organismos Geneticamente Modificados , RNA de Transferência/metabolismo
14.
Breed Sci ; 73(3): 261-268, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37840973

RESUMO

Ear tip-barrenness (ETB), which results from aborted kernels or infertile florets at the ear tip, is an undesirable factor affecting the yield and quality of waxy maize. To uncover the genetic basis of ETB, a genome-wide association study (GWAS) was conducted using the genotype with 27,354 SNPs and phenotype with three environments. Five SNPs that distributed on chromosomes 1, 3 and 6, were identified to be significantly associated with ETB based on the threshold of false discovery rate (FDR) at 0.05. Among these significant loci, three SNPs were clustered together and colocalized with genomic regions previously reported. The average length of ETB decreased almost linearly from the inbred lines containing no favorable alleles across the three loci (1.75 cm) to those with one (1.18 cm), two (0.94 cm) and three (0.65 cm) favorable alleles. Moreover, three important genes, Zm00001d030028, Zm00001d041510 and Zm00001d038676 were predicted for three significant QTLs, respectively. These results promote the understanding genetic basis for ETB and will be useful for breeding waxy maize varieties with high-quality and high-yield.

15.
Front Plant Sci ; 14: 1279896, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37885658

RESUMO

Bacillus velezensis strain GB03 is a Gram-positive rhizosphere bacterium known for its ability to promote plant growth and immunity. This review provides a comprehensive overview of the research on GB03 from its initial discovery in Australian wheat fields in 1971 to its current applications. Recognized as a model plant growth-promoting rhizobacterium (PGPR), GB03 has exhibited outstanding performance in enhancing the growth and protection of many crop plants including cucumber, pepper, wheat, barley, soybean, and cotton. Notably, GB03 has been reported to elicit plant immune response, referred to as induced systemic resistance (ISR), against above-ground pathogens and insect pests. Moreover, a pivotal finding in GB03 was the first-ever identification of its bacterial volatile compounds, which are known to boost plant growth and activate ISR. Research conducted over the past five decades has clearly demonstrated the potential of GB03 as an eco-friendly substitute for conventional pesticides and fertilizers. Validating its safety, the U.S. Environmental Protection Agency endorsed GB03 for commercial use as Kodiak® in 1998. Subsequently, other compounds, such as BioYield™, were released as a biological control agent against soil-borne pathogens and as a biofertilizer, utilizing a durable spore formulation. More recently, GB03 has been utilized as a keystone modulator for engineering the rhizosphere microbiome and for eliciting microbe-induced plant volatiles. These extensive studies on GB03 underscore its significant role in sustainable agriculture, positioning it as a safe and environmentally-friendly solution for crop protection.

16.
Comput Struct Biotechnol J ; 21: 5066-5072, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37867972

RESUMO

Medicinal plants are rich in secondary metabolites with beneficial pharmacological effects. The production of plant secondary metabolites is subjected to the influences by environmental factors including the plant-associated microbiome, which is crucial to the host's fitness and survival. As a result, research interests are increasing in exploiting microbial capacities for enhancing plant production of pharmacological metabolites. A growing body of recent research provides accumulating evidence in support of developing microbe-based tools for achieving this objective. This mini review presents brief summaries of recent studies on medicinal plants that demonstrate microbe-augmented production of pharmacological terpenoids, polyphenols, and alkaloids, followed by discussions on some key questions beyond the promising observations. Explicit molecular insights into the underlying mechanisms will enhance microbial applications for metabolic fortification in medicinal plants.

17.
Clin Lab ; 69(8)2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-37560858

RESUMO

BACKGROUND: Congenital nephrotic syndrome (CNS) of the Finnish type (CNF) is an autosomal recessively disorder. NPHS1 gene mutation is the main gene responsible for CNF. This study aimed to explore the clinical manifestations and the characteristics of genetic variation in Chinese patients with CNS. METHODS: A 15-minute-old boy and a 34-day-old girl with CNS were included. NPHS1 gene was detected by next-generation high-throughput sequencing. RESULTS: Patient 1 carried two novel heterozygous mutations of NPHS1 gene, one was c.204delG, p. (Leu69fs) in exon 2 of NPHS1 gene, a heterozygote frameshift mutation; the other was c.3558delT, p. (Gly1187fs) in exon 28, a heterozygote frameshift mutation. Patient 2 carried three heterozygous mutations of NPHS1, among them, c.1561-G>A. p.Asp521Asn in exon 12 is a heterozygous missense mutation. It was identified as possible de novo pathogenicity gene. CONCLUSIONS: Three novel heterozygous mutations of NPHS1 gene were responsible for the patients with CNS and can enlarge the spectrum of NPHS1 gene mutation.


Assuntos
Síndrome Nefrótica , Feminino , Humanos , Lactente , Masculino , População do Leste Asiático , Heterozigoto , Proteínas de Membrana/genética , Mutação , Síndrome Nefrótica/diagnóstico , Síndrome Nefrótica/genética , Recém-Nascido
18.
Front Immunol ; 14: 1158883, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37207234

RESUMO

Background: Vitiligo is an autoimmune skin disease mainly mediated by CD8+ T cells, which affects about 0.1%-2% population of the world. Leptin plays a critical role in regulating the activation of CD8+ T cells. However, the effect of Leptin on vitiligo remains unclear. Objectives: To explore the effect of leptin on CD8+ T cells and its influence on vitiligo. Methods: RNA sequencing and Quantitative Real-time PCR (RT-qPCR) were used to explore the differentially expressed genes. Immunofluorescence staining was performed on skin lesions. Leptin in serum was detected by enzyme linked immunosorbent assay (ELISA). The peripheral blood mononuclear cells were detected by flow cytometry after leptin stimulation for 72 hours. A vitiligo model was established by monobenzone on Leptin KO mice. Results: 557 differentially expressed genes were found, including 154 up-regulated and 403 down-regulated genes. Lipid metabolism pathways showed a close relationship to the pathogenesis of vitiligo, especially the PPAR signaling pathway. RT-qPCR (p = 0.013) and immunofluorescence staining (p = 0.0053) verified that LEPR expressed significantly higher in vitiligo. The serum leptin level of vitiligo patients was significantly lower than that of healthy controls (p = 0.0245). The interferon-γ subset of CD8+LEPR+ T cells from vitiligo patients was significantly higher (p = 0.0189). The protein level of interferon-γ was significantly increased after leptin stimulation in vitro (p = 0.0217). In mice, Leptin deficiency resulted in less severe hair depigmentation. Leptin deficiency also resulted in significantly lower expressed vitiligo-related genes, such as Cxcl9 (p = 0.0497), Gzmb (p < 0.001), Ifng (p = 0.0159), and Mx1 (p < 0.001) after modeling. Conclusion: Leptin could promote the progression of vitiligo by enhancing the cytotoxic function of CD8+ T cells. Leptin may become a new target for vitiligo treatment.


Assuntos
Linfócitos T CD8-Positivos , Vitiligo , Animais , Camundongos , Interferon gama/metabolismo , Granzimas/metabolismo , Leptina/metabolismo , Leucócitos Mononucleares/metabolismo
19.
Tomography ; 9(3): 931-941, 2023 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-37218936

RESUMO

Genetically engineered mouse models (GEMMs) and patient-derived xenograft mouse models (PDXs) can recapitulate important biological features of cancer. They are often part of precision medicine studies in a co-clinical setting, in which therapeutic investigations are conducted in patients and in parallel (or sequentially) in cohorts of GEMMs or PDXs. Employing radiology-based quantitative imaging in these studies allows in vivo assessment of disease response in real time, providing an important opportunity to bridge precision medicine from the bench to the bedside. The Co-Clinical Imaging Research Resource Program (CIRP) of the National Cancer Institute focuses on the optimization of quantitative imaging methods to improve co-clinical trials. The CIRP supports 10 different co-clinical trial projects, spanning diverse tumor types, therapeutic interventions, and imaging modalities. Each CIRP project is tasked to deliver a unique web resource to support the cancer community with the necessary methods and tools to conduct co-clinical quantitative imaging studies. This review provides an update of the CIRP web resources, network consensus, technology advances, and a perspective on the future of the CIRP. The presentations in this special issue of Tomography were contributed by the CIRP working groups, teams, and associate members.


Assuntos
Neoplasias , Medicina de Precisão , Estados Unidos , Humanos , Animais , Camundongos , Medicina de Precisão/métodos , National Cancer Institute (U.S.) , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Modelos Animais de Doenças
20.
J Phys Chem Lett ; 14(16): 3853-3860, 2023 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-37067229

RESUMO

The shape effect of thermoplasmonic properties of Au nanostructures remains largely unexplored. Herein, we report a systematic investigation on the photothermal effects of Au nanoparticles (NPs) of different shapes: nanosphere, nanocube, nanorod, nanostar, and nanobipyramid. The Joule (Jo) number (absorption cross section normalized by the particulate volume) is utilized for quantitatively assessing the photothermal properties of these different shaped Au NPs. It is shown that the Jo number of Au NPs greatly varies with the geometric shape and localized surface plasmon resonance (LSPR) wavelength. Specifically, the Jo number decreases with the red-shifting of the LSPR wavelength in these Au NPs, and the Au NPs of sharp structural features such as Au nanorod, nanostar and nanobipyramid have a much larger Jo number, indicative of their exceptional light-to-heat conversion ability. We further demonstrate the close correlation of the Jo number of Au NPs of different shapes with their optical absorption power density.

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