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1.
Cell ; 186(7): 1478-1492.e15, 2023 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-36870331

RESUMO

Lungs undergo mechanical strain during breathing, but how these biophysical forces affect cell fate and tissue homeostasis are unclear. We show that biophysical forces through normal respiratory motion actively maintain alveolar type 1 (AT1) cell identity and restrict these cells from reprogramming into AT2 cells in the adult lung. AT1 cell fate is maintained at homeostasis by Cdc42- and Ptk2-mediated actin remodeling and cytoskeletal strain, and inactivation of these pathways causes a rapid reprogramming into the AT2 cell fate. This plasticity induces chromatin reorganization and changes in nuclear lamina-chromatin interactions, which can discriminate AT1 and AT2 cell identity. Unloading the biophysical forces of breathing movements leads to AT1-AT2 cell reprogramming, revealing that normal respiration is essential to maintain alveolar epithelial cell fate. These data demonstrate the integral function of mechanotransduction in maintaining lung cell fate and identifies the AT1 cell as an important mechanosensor in the alveolar niche.


Assuntos
Células Epiteliais Alveolares , Mecanotransdução Celular , Células Epiteliais Alveolares/metabolismo , Células Cultivadas , Pulmão , Diferenciação Celular/fisiologia , Respiração
2.
Cell ; 170(6): 1134-1148.e10, 2017 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-28886382

RESUMO

The lung is an architecturally complex organ comprising a heterogeneous mixture of various epithelial and mesenchymal lineages. We use single-cell RNA sequencing and signaling lineage reporters to generate a spatial and transcriptional map of the lung mesenchyme. We find that each mesenchymal lineage has a distinct spatial address and transcriptional profile leading to unique niche regulatory functions. The mesenchymal alveolar niche cell is Wnt responsive, expresses Pdgfrα, and is critical for alveolar epithelial cell growth and self-renewal. In contrast, the Axin2+ myofibrogenic progenitor cell preferentially generates pathologically deleterious myofibroblasts after injury. Analysis of the secretome and receptome of the alveolar niche reveals functional pathways that mediate growth and self-renewal of alveolar type 2 progenitor cells, including IL-6/Stat3, Bmp, and Fgf signaling. These studies define the cellular and molecular framework of lung mesenchymal niches and reveal the functional importance of developmental pathways in promoting self-renewal versus a pathological response to tissue injury.


Assuntos
Pulmão/citologia , Mesoderma/citologia , Algoritmos , Animais , Células Epiteliais/metabolismo , Fibrose/metabolismo , Perfilação da Expressão Gênica , Pulmão/patologia , Pulmão/fisiologia , Lesão Pulmonar/patologia , Camundongos , Organoides/citologia , Comunicação Parácrina , Regeneração , Transdução de Sinais , Análise de Célula Única , Células-Tronco/metabolismo
3.
Nature ; 604(7904): 120-126, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35355013

RESUMO

The human lung differs substantially from its mouse counterpart, resulting in a distinct distal airway architecture affected by disease pathology in chronic obstructive pulmonary disease. In humans, the distal branches of the airway interweave with the alveolar gas-exchange niche, forming an anatomical structure known as the respiratory bronchioles. Owing to the lack of a counterpart in mouse, the cellular and molecular mechanisms that govern respiratory bronchioles in the human lung remain uncharacterized. Here we show that human respiratory bronchioles contain a unique secretory cell population that is distinct from cells in larger proximal airways. Organoid modelling reveals that these respiratory airway secretory (RAS) cells act as unidirectional progenitors for alveolar type 2 cells, which are essential for maintaining and regenerating the alveolar niche. RAS cell lineage differentiation into alveolar type 2 cells is regulated by Notch and Wnt signalling. In chronic obstructive pulmonary disease, RAS cells are altered transcriptionally, corresponding to abnormal alveolar type 2 cell states, which are associated with smoking exposure in both humans and ferrets. These data identify a distinct progenitor in a region of the human lung that is not found in mouse that has a critical role in maintaining the gas-exchange compartment and is altered in chronic lung disease.


Assuntos
Bronquíolos , Furões , Células-Tronco Multipotentes , Alvéolos Pulmonares , Animais , Bronquíolos/citologia , Linhagem da Célula , Humanos , Pulmão/patologia , Camundongos , Células-Tronco Multipotentes/citologia , Alvéolos Pulmonares/citologia , Doença Pulmonar Obstrutiva Crônica
4.
Genes Dev ; 33(11-12): 656-668, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-30923168

RESUMO

Transcription factors (TFs) are dosage-sensitive master regulators of gene expression, with haploinsufficiency frequently leading to life-threatening disease. Numerous mechanisms have evolved to tightly regulate the expression and activity of TFs at the transcriptional, translational, and posttranslational levels. A subset of long noncoding RNAs (lncRNAs) is spatially correlated with transcription factors in the genome, but the regulatory relationship between these lncRNAs and their neighboring TFs is unclear. We identified a regulatory feedback loop between the TF Foxa2 and a downstream lncRNA, Falcor (Foxa2-adjacent long noncoding RNA). Foxa2 directly represses Falcor expression by binding to its promoter, while Falcor functions in cis to positively regulate the expression of Foxa2. In the lung, loss of Falcor is sufficient to lead to chronic inflammatory changes and defective repair after airway epithelial injury. Moreover, disruption of the Falcor-Foxa2 regulatory feedback loop leads to altered cell adhesion and migration, in turn resulting in chronic peribronchial airway inflammation and goblet cell metaplasia. These data reveal that the lncRNA Falcor functions within a regulatory feedback loop to fine-tune the expression of Foxa2, maintain airway epithelial homeostasis, and promote regeneration.


Assuntos
Células Epiteliais/metabolismo , Fator 3-beta Nuclear de Hepatócito/genética , Pulmão/citologia , Pulmão/metabolismo , RNA Longo não Codificante/genética , Animais , Adesão Celular , Linhagem Celular , Movimento Celular , Feminino , Regulação da Expressão Gênica , Fator 3-beta Nuclear de Hepatócito/metabolismo , Homeostase , Humanos , Masculino , Camundongos , Regiões Promotoras Genéticas , Regeneração , Transcrição Gênica
5.
J Am Chem Soc ; 146(28): 19261-19270, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-38950118

RESUMO

Enantioselective construction of all-carbon quaternary stereocenters has attracted much attention over the past few decades. A variety of catalytic asymmetric methods have been disclosed based on the use of presynthesized complex reagents that impart congested steric hindrance to the reaction center, which generally produce the chiral molecules through forming one C-C bond. The use of readily available reagents that could build two C-C bonds on the same carbonic center with the concomitant assembly of quaternary stereocenters remains challenging. Herein, we disclose a catalytic asymmetric alkyne multifunctionalization reaction using a gold complex and a chiral spiro phosphoric acid (SPA) for synergistic catalysis. In this method, the readily accessible internal alkynes served as the key gold carbene precursors, followed by carbene gem-dialkylation through Mannich-type addition of enolate species or stepwise formal cycloaddition with methylenimines that are derived from 1,3,5-triazinanes in the presence of SPA. The reaction provides practical access to poly-functionalized chiral linear and cyclic ketones that bear two adjacent quaternary stereocenters in generally good yields and excellent enantioselectivities, leading to an essential complement to the asymmetric construction of quaternary stereocenters using readily available materials with high bond formation efficiency.

6.
Opt Lett ; 49(8): 1908-1910, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38621036

RESUMO

Stable reproducibility of mechanoluminescence (ML) is of vital importance for trap-controlled ML materials. Photo/electric excitation is usually needed for ML recovery of trap-controlled materials. In this work, it is demonstrated that thermal treatment can be applied to achieve recovery of ML, which is ascribed to the unique trap level configuration. The Ca6BaP4O17:Eu2+ performing robust trap-controlled ML has been proposed, and the corresponding repetitive ML can be realized by thermal treatment. TL spectra reveal that the thermally induced reproducible ML benefits from the dual defect level electronic structure of Ca6BaP4O17:Eu2+. The ML intensity is dependent on the electrons in shallow traps, and the electron transfer from deep traps to shallow traps induced by thermal treatment leads to repetitive ML.

7.
Chemistry ; 30(21): e202304152, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38311589

RESUMO

Due to the ultrahigh theoretical specific capacity (3860 mAh g-1) and low redox potential (-3.04 V vs. standard hydrogen electrode), Lithium (Li) metal anode (LMA) received increasing attentions. However, notorious dendrite and volume expansion during the cycling process seriously hinder the development of high energy density Li metal batteries. Constructing three-dimensional (3D) current collectors for Li can fundamentally solve the intrinsic drawback of hostless for Li. Therefore, this review systematically introduces the design and synthesis engineering and the current development status of different 3D collectors in recent years (the current collectors are divided into two major parts: metal-based current collectors and carbon-based current collectors). In the end, some perspectives of the future promotion for LMA application are also presented.

8.
BMC Cancer ; 24(1): 671, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38824581

RESUMO

BACKGROUND: The role of novel circular RNAs (circRNAs) in colorectal cancer (CRC) remains to be determined. This study aimed to identify a novel circRNA involved in CRC pathogenesis, assess its diagnostic value, and construct a regulatory network. METHODS: Differential expression analysis was conducted using circRNA datasets to screen for differentially expressed circRNAs. The expression of selected circRNAs was validated in external datasets and clinical samples. Diagnostic value of plasma circRNA levels in CRC was assessed. A competing endogenous RNA (ceRNA) network was constructed for the circRNA using TCGA dataset. RESULTS: Analysis of datasets revealed that hsa_circ_101303 was significantly overexpressed in CRC tissues compared to normal tissues. The upregulation of hsa_circ_101303 in CRC tissues was further confirmed through the GSE138589 dataset and clinical samples. High expression of hsa_circ_101303 was associated with advanced N stage, M stage, and tumor stage in CRC. Plasma levels of hsa_circ_101303 were markedly elevated in CRC patients and exhibited moderate diagnostic ability for CRC (AUC = 0.738). The host gene of hsa_circ_101303 was also found to be related to the TNM stage of CRC. Nine miRNAs were identified as target miRNAs for hsa_circ_101303, and 27 genes were identified as targets of these miRNAs. Subsequently, a ceRNA network for hsa_circ_101303 was constructed to illustrate the interactions between the nine miRNAs and 27 genes. CONCLUSIONS: The study identifies hsa_circ_101303 as a highly expressed circRNA in CRC, which is associated with the progression of the disease. Plasma levels of hsa_circ_101303 show promising diagnostic potential for CRC. The ceRNA network for hsa_circ_101303 provides valuable insights into the regulatory mechanisms underlying CRC.


Assuntos
Biomarcadores Tumorais , Neoplasias Colorretais , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , MicroRNAs , RNA Circular , Humanos , Neoplasias Colorretais/genética , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/sangue , Neoplasias Colorretais/patologia , RNA Circular/genética , RNA Circular/sangue , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/sangue , Masculino , Feminino , MicroRNAs/genética , MicroRNAs/sangue , Pessoa de Meia-Idade , Perfilação da Expressão Gênica , Estadiamento de Neoplasias
9.
Fish Shellfish Immunol ; 153: 109836, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39147177

RESUMO

Pseudomonas plecoglossicida is one of most important pathogenic bacterial species in large yellow croaker and several other commercially valuable fish species. In our previous study, a GacS deficient mutant (ΔgacS) was constructed and its virulence showed substantially attenuated. In present study, the safety, immunogenicity and protective effect of the ΔgacS were evaluated in large yellow croaker as a live-attenuated vaccine candidate. It was shown that the ΔgacS strain exhibited good safety to large yellow croaker and there was no mortality or clinical symptoms observed in all fish that infected by ΔgacS strain with the doses range from 2 × 105~107 CFU per fish via intraperitoneal injection (IP) or immersion (IM), and almost all bacteria were cleaned up in the spleen of the fish at 14-day post infection. Specific antibodies could be detected at 7-day and 14-day post infection by direct agglutination method, and the valences of antibodies and bactericidal activities of the serum were significant increased with vaccination doses and vaccination time. Moreover, the expressions of some molecules and cytokines involved in specific immune responses were detected in the ΔgacS strain immunization group and control group. After challenged by the wild-type (WT) strain XSDHY-P, the relative percentage survival (RPS) showed highly correlated with the immunized dosage regardless of vaccination methods. It showed that the RPS of the IP groups were 39.47 %, 57.89 %, 71.05 % with the immune dosage in a descending order, respectively, and the RPS of the IM groups were 26.31 %, 36.84 %, 76.31 % with the immune dosage in a descending order, respectively. In summary, the ΔgacS strain exhibited safety and good protective effect to large yellow croaker and was a potential live vaccine candidate.


Assuntos
Doenças dos Peixes , Perciformes , Infecções por Pseudomonas , Pseudomonas , Vacinas Atenuadas , Animais , Doenças dos Peixes/imunologia , Doenças dos Peixes/prevenção & controle , Perciformes/imunologia , Vacinas Atenuadas/imunologia , Vacinas Atenuadas/administração & dosagem , Infecções por Pseudomonas/veterinária , Infecções por Pseudomonas/prevenção & controle , Infecções por Pseudomonas/imunologia , Pseudomonas/imunologia , Vacinas Bacterianas/imunologia , Vacinas Bacterianas/administração & dosagem , Vacinas contra Pseudomonas/imunologia , Vacinas contra Pseudomonas/genética , Imunogenicidade da Vacina
10.
Fish Shellfish Immunol ; 145: 109355, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38168634

RESUMO

The scavenger receptor class B family proteins (SRB) are multiligand membrane receptor proteins. Herein, a novel SRB homolog (Pt-SRB2) was identified in Portunus trituberculatus. The open reading frame of Pt-SRB2 was predicted to encode 520 amino acid residues comprising a typical CD36 domain. Phylogenetic analysis showed that Pt-SRB2 distinctly clustered with the SRB homologs of most crustaceans and Drosophila but was separate from all vertebrate CD36/SRB. Semi-quantitative and Real-time quantitative PCR revealed that the abundance of Pt-SRB2 transcripts was the highest in hepatopancreas than in other tested tissues. Overexpressed Pt-SRB2 was distributed primarily in the cell membrane and cytoplasm of HEK293T or Drosophila Schneider 2 cells. In crab hemocytes, Pt-SRB2 was distributed primarily in the cell membrane by immunofluorescence staining. In addition, the immunofluorescence staining showed that green fluorescence signals were mainly located in the inner lumen membrane of the hepatopancreatic tubules. Moreover, solid-phase enzyme-linked immunosorbent assay revealed that rPt-SRB2-L exhibited relative high affinity with lipopolysaccharides, and relative moderate binding affinity with lipoteichoic acid or peptidoglycan. Of note, rPt-SRB2-L showed high binding affinity with eicosapentaenoic acid among a series of long-chain polyunsaturated fatty acids. Taken together, this study provided valuable data for understanding the functions of the crab CD36/SRB.


Assuntos
Braquiúros , Antígenos CD36 , Humanos , Animais , Antígenos CD36/genética , Braquiúros/genética , Sequência de Aminoácidos , Sequência de Bases , Filogenia , Células HEK293 , Drosophila/metabolismo
11.
Nature ; 555(7695): 251-255, 2018 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-29489752

RESUMO

Functional tissue regeneration is required for the restoration of normal organ homeostasis after severe injury. Some organs, such as the intestine, harbour active stem cells throughout homeostasis and regeneration; more quiescent organs, such as the lung, often contain facultative progenitor cells that are recruited after injury to participate in regeneration. Here we show that a Wnt-responsive alveolar epithelial progenitor (AEP) lineage within the alveolar type 2 cell population acts as a major facultative progenitor cell in the distal lung. AEPs are a stable lineage during alveolar homeostasis but expand rapidly to regenerate a large proportion of the alveolar epithelium after acute lung injury. AEPs exhibit a distinct transcriptome, epigenome and functional phenotype and respond specifically to Wnt and Fgf signalling. In contrast to other proposed lung progenitor cells, human AEPs can be directly isolated by expression of the conserved cell surface marker TM4SF1, and act as functional human alveolar epithelial progenitor cells in 3D organoids. Our results identify the AEP lineage as an evolutionarily conserved alveolar progenitor that represents a new target for human lung regeneration strategies.


Assuntos
Células Epiteliais/citologia , Evolução Molecular , Alvéolos Pulmonares/citologia , Regeneração , Células-Tronco/citologia , Lesão Pulmonar Aguda/patologia , Lesão Pulmonar Aguda/cirurgia , Animais , Antígenos de Superfície/metabolismo , Proteína Axina/metabolismo , Biomarcadores/metabolismo , Ciclo Celular , Linhagem da Célula , Cromatina/genética , Cromatina/metabolismo , Epigenômica , Células Epiteliais/metabolismo , Feminino , Fatores de Crescimento de Fibroblastos/metabolismo , Humanos , Masculino , Camundongos , Proteínas de Neoplasias/metabolismo , Organoides/citologia , Organoides/metabolismo , Células-Tronco/metabolismo , Transcriptoma , Via de Sinalização Wnt
12.
Int J Med Sci ; 21(6): 1079-1090, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38774751

RESUMO

Idiopathic pulmonary fibrosis (IPF) is a rare, chronic and progressively worsening lung disease that poses a significant threat to patient prognosis, with a mortality rate exceeding that of some common malignancies. Effective methods for early diagnosis and treatment remain for this condition are elusive. In our study, we used the GEO database to access second-generation sequencing data and associated clinical information from IPF patients. By utilizing bioinformatics techniques, we identified crucial disease-related genes and their biological functions, and characterized their expression patterns. Furthermore, we mapped out the immune landscape of IPF, which revealed potential roles for novel kinase 1 and CD8+T cells in disease progression and outcome. These findings can aid the development of new strategies for the clinical diagnosis and treatment of IPF.


Assuntos
Linfócitos T CD8-Positivos , Fibrose Pulmonar Idiopática , Humanos , Linfócitos T CD8-Positivos/imunologia , Biologia Computacional , Progressão da Doença , Fibrose Pulmonar Idiopática/genética , Fibrose Pulmonar Idiopática/imunologia , Fibrose Pulmonar Idiopática/patologia , Prognóstico
13.
BMC Womens Health ; 24(1): 297, 2024 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-38762459

RESUMO

OBJECTIVE: The aim of this study is to explore the efficacy and safety of chemotherapy (CT) as a monotherapy in patients with recurrent intermediate/high-risk factors following radical hysterectomy for stage IB-IIA cervical cancer. METHODS: A retrospective analysis was conducted on the medical records of patients diagnosed with stage IB-IIA cervical cancer who underwent radical hysterectomy at the People's Hospital of Suzhou High-tech District between 2010 and 2020. A total of 66 patients with intermediate or high-risk factors for recurrence were treated exclusively with CT. This cohort included 42 patients in the intermediate-risk group and 24 in the high-risk group. Treatment protocols consisted of 4-6 cycles of paclitaxel and cisplatin drugs for the intermediate-risk group, and 6 cycles for the high-risk group. The relapse-free survival (RFS), recurrence rates, and common CT-related adverse reactions, including bone marrow suppression, nausea and vomiting, and diarrhea, were assessed for both groups. RESULTS: (1) The cumulative 3-year RFS rates for the intermediate-risk and high-risk groups were 97.3% (36/37) and 82.4% (14/17), respectively, with cumulative 5-year RFS rates of 97.1% (34/35) and 82.4% (14/17), respectively. The Log rank test revealed no significant difference between the two groups (P > 0.05), (χ² = 2.718, P = 0.099). The 5-year recurrence rates in the intermediate-risk and high-risk groups were 2.38% (1/42) and 12.50% (3/24), respectively. (2) The incidence of grade III bone marrow suppression in the intermediate-risk and high-risk groups was 21.19% (11/42) and 25.00% (6/24), respectively, while the incidence of grade IV bone marrow suppression was 11.90% (5/42) and 8.33% (2/24), respectively. There was no statistically significant difference in bone marrow suppression grades between the two groups (P > 0.05). CONCLUSION: CT with paclitaxel and cisplatin, administered as monotherapy post-radical hysterectomy for stage IB-IIA cervical cancer, demonstrates satisfactory survival benefits with an acceptable safety profile. Moreover, no significant differences were observed in prognosis or adverse reactions between the different risk groups treated solely with CT.


Assuntos
Cisplatino , Histerectomia , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Paclitaxel , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/cirurgia , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/patologia , Estudos Retrospectivos , Histerectomia/métodos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Adulto , Paclitaxel/uso terapêutico , Cisplatino/uso terapêutico , Cisplatino/administração & dosagem , Fatores de Risco , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Idoso , Antineoplásicos/uso terapêutico
14.
Skin Res Technol ; 30(8): e13783, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39113617

RESUMO

BACKGROUND: In recent years, the increasing prevalence of skin cancers, particularly malignant melanoma, has become a major concern for public health. The development of accurate automated segmentation techniques for skin lesions holds immense potential in alleviating the burden on medical professionals. It is of substantial clinical importance for the early identification and intervention of skin cancer. Nevertheless, the irregular shape, uneven color, and noise interference of the skin lesions have presented significant challenges to the precise segmentation. Therefore, it is crucial to develop a high-precision and intelligent skin lesion segmentation framework for clinical treatment. METHODS: A precision-driven segmentation model for skin cancer images is proposed based on the Transformer U-Net, called BiADATU-Net, which integrates the deformable attention Transformer and bidirectional attention blocks into the U-Net. The encoder part utilizes deformable attention Transformer with dual attention block, allowing adaptive learning of global and local features. The decoder part incorporates specifically tailored scSE attention modules within skip connection layers to capture image-specific context information for strong feature fusion. Additionally, deformable convolution is aggregated into two different attention blocks to learn irregular lesion features for high-precision prediction. RESULTS: A series of experiments are conducted on four skin cancer image datasets (i.e., ISIC2016, ISIC2017, ISIC2018, and PH2). The findings show that our model exhibits satisfactory segmentation performance, all achieving an accuracy rate of over 96%. CONCLUSION: Our experiment results validate the proposed BiADATU-Net achieves competitive performance supremacy compared to some state-of-the-art methods. It is potential and valuable in the field of skin lesion segmentation.


Assuntos
Melanoma , Neoplasias Cutâneas , Humanos , Neoplasias Cutâneas/diagnóstico por imagem , Neoplasias Cutâneas/patologia , Melanoma/diagnóstico por imagem , Melanoma/patologia , Algoritmos , Redes Neurais de Computação , Processamento de Imagem Assistida por Computador/métodos , Interpretação de Imagem Assistida por Computador/métodos , Dermoscopia/métodos , Aprendizado Profundo
15.
J Fish Dis ; 47(3): e13896, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38054569

RESUMO

Nocardia seriolae is the primary aetiological agent of nocardiosis in fish, which causes mass mortality in freshwater and marine fish. ß-ketoacyl-ACP synthase (KAS) is one of the essential enzymes in the synthesis of mycolic acids (MASs) in Mycobacterium spp. and has been chosen as the target for therapeutic intervention in mycobacterial diseases. In the present study, a kasB homologue gene (kasB) was identified in the genome of N. seriolae, and the gene-deficient mutant (ΔkasB) was generated based on a clinical isolate, XSYC-Ns. Compared to the wild-type (WT) strain, the ΔkasB showed a measurably growth defect in vitro but retained the acid-fastness in acid-fast staining. Observation of the cell ultrastructure showed some alterations in the cell wall of the ΔkasB strain. Compared to its original strain, the cell wall lipid layer seemed sparser, and a wider electron-transparent zone was observed in the cell wall of ΔkasB strain. Moreover, the ΔkasB strain showed impaired ability of cell invasion as well as intracellular survival in the cell line originating from the head-kidney of the large yellow croaker (LYC-hK), compared to its original strain. In addition, the deficiency of ΔkasB significantly attenuated the virulence of N. seriolae in largemouth bass. The present study suggested that the ΔkasB gene might be involved in the synthesis of extracellular cell-wall lipids in N. seriolae and play a crucial role in its pathogenicity.


Assuntos
Bass , Doenças dos Peixes , Nocardiose , Nocardia , Animais , Virulência/genética , Doenças dos Peixes/microbiologia , Nocardia/genética , Nocardiose/veterinária , Nocardiose/microbiologia
16.
Zhongguo Zhong Yao Za Zhi ; 49(5): 1275-1285, 2024 Mar.
Artigo em Zh | MEDLINE | ID: mdl-38621975

RESUMO

This study aims to investigate the regulatory effects of Shenling Baizhu Powder(SBP) on cellular autophagy in alcoholic liver disease(ALD) and its intervention effect through the TLR4/NLRP3 pathway. A rat model of chronic ALD was established by gavage of spirits. An ALD cell model was established by stimulating BRL3A cells with alcohol. High-performance liquid chromatography(HPLC) was utilized for the compositional analysis of SBP. Liver tissue from ALD rats underwent hematoxylin-eosin(HE) and oil red O staining for pathological evaluation. Enzyme-linked immunosorbent assay(ELISA) was applied to quantify lipopolysaccharides(LPS), tumor necrosis factor-alpha(TNF-α), interleukin-1 beta(IL-1ß), and interleukin-18(IL-18) levels. Quantitative reverse transcription polymerase chain reaction(qRT-PCR) was conducted to evaluate the mRNA expression of myeloid differentiation factor 88(MyD88) and Toll-like receptor 4(TLR4). The effect of different drugs on BRL3A cell proliferation activity was assessed through CCK-8 analysis. Western blot analysis was performed to examine the protein expression of NOD-like receptor pyrin domain-containing 3(NLRP3), nuclear factor-kappa B P65(NF-κB P65), phosphorylated nuclear factor-kappa B P65(p-P65), caspase-1, P62, Beclin1, and microtubule-associated protein 1 light chain 3(LC3Ⅱ). The results showed that SBP effectively ameliorated hepatic lipid accumulation, reduced liver function, mitigated hepatic tissue inflammation, and reduced levels of LPS, TNF-α, IL-1ß, and IL-18. Moreover, SBP exhibited the capacity to modulate hepatic autophagy induced by prolonged alcohol intake through the TLR4/NLRP3 signaling pathway. This modulation resulted in decreased expression of LC3Ⅱ and Beclin1, an elevation in P62 expression, and the promotion of autolysosome formation. These research findings imply that SBP can substantially enhance liver function and mitigate lipid irregularities in the context of chronic ALD. It achieves this by regulating excessive autophagic responses caused by prolonged spirit consumption, primarily through the inhibition of the TLR4/NLRP3 pathway.


Assuntos
Medicamentos de Ervas Chinesas , Hepatopatias Alcoólicas , Proteína 3 que Contém Domínio de Pirina da Família NLR , Ratos , Animais , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Interleucina-18 , Pós , Lipopolissacarídeos , Fator de Necrose Tumoral alfa , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Proteína Beclina-1 , NF-kappa B/metabolismo , Hepatopatias Alcoólicas/tratamento farmacológico , Hepatopatias Alcoólicas/genética
17.
J Neurochem ; 165(2): 268-276, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36776136

RESUMO

Studies have shown that rapid eye movement (REM) sleep behavior disorder (RBD) is a subtype of Parkinson's disease (PD) characterized by severe cognitive impairment and rapid disease progression. However, reliable biological markers are lacking presently. Neurofilament light chain (NFL) and glial fibrillary acidic protein (GFAP) have been widely studied as biomarkers of cognition impairment. This study aimed to find biomarkers for the RBD subtype of PD by investigating the possible relationship between serum NFL, GFAP levels, and the RBD subtype. A total of 109 PD patients and 37 healthy controls (HCs) were included, and their clinical characteristics were evaluated. PD patients were divided into two groups based on whether they had probable RBD or not. Serum NFL and GFAP levels were measured using the ultrasensitive single molecule array (Simoa) platform. The obtained data were statistically analyzed using SPSS 25.0 (IBM, Chicago, IL, USA). NFL and GFAP in the PD-RBD group were elevated compared with the PD-nRBD and control groups. Moreover, serum NFL and GFAP levels positively correlated with RBD. The combination of NFL and GFAP showed good performance in identifying PD-RBD patients from PD-nRBD. After considering potential confounding factors such as age, and disease duration, serum NFL and GFAP emerged as independent risk factors for RBD. Serum NFL and GFAP were related to RBD in PD patients. Concludingly, serum NFL and GFAP might serve as promising biomarkers for the RBD subtype of PD.


Assuntos
Proteínas de Neurofilamentos , Doença de Parkinson , Transtorno do Comportamento do Sono REM , Humanos , Biomarcadores , Proteína Glial Fibrilar Ácida , Filamentos Intermediários/química , Proteínas de Neurofilamentos/sangue , Proteínas de Neurofilamentos/química , Doença de Parkinson/complicações , Transtorno do Comportamento do Sono REM/diagnóstico
18.
Mol Hum Reprod ; 29(5)2023 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-36892447

RESUMO

Semaphorins are a family of evolutionarily conserved morphogenetic molecules that were initially found to be associated with axonal guidance. Semaphorin 4C (Sema4C), a member of the fourth subfamily of semaphorins, has been demonstrated to play multifaceted and important roles in organ development, immune regulation, tumor growth, and metastasis. However, it is completely unknown whether Sema4C is involved in the regulation of ovarian function. We found that Sema4C was widely expressed in the stroma, follicles, and corpus luteum of mouse ovaries, and its expression was decreased at distinct foci in ovaries of mice of mid-to-advanced reproductive age. Inhibition of Sema4C by the ovarian intrabursal administration of recombinant adeno-associated virus-shRNA significantly reduced oestradiol, progesterone, and testosterone levels in vivo. Transcriptome sequencing analysis showed changes in pathways related to ovarian steroidogenesis and the actin cytoskeleton. Similarly, knockdown of Sema4C by siRNA interference in mouse primary ovarian granulosa cells or thecal interstitial cells significantly suppressed ovarian steroidogenesis and led to actin cytoskeleton disorganization. Importantly, the cytoskeleton-related pathway RHOA/ROCK1 was simultaneously inhibited after the downregulation of Sema4C. Furthermore, treatment with a ROCK1 agonist after siRNA interference stabilized the actin cytoskeleton and reversed the inhibitory effect on steroid hormones described above. In conclusion, Sema4C may play an important role in ovarian steroidogenesis through regulation of the actin cytoskeleton via the RHOA/ROCK1 signaling pathway. These findings shed new light on the identification of dominant factors involved in the endocrine physiology of female reproduction.


Assuntos
Ovário , Semaforinas , Animais , Feminino , Camundongos , Citoesqueleto de Actina/metabolismo , Ovário/metabolismo , RNA Interferente Pequeno/genética , Semaforinas/genética , Semaforinas/metabolismo , Transdução de Sinais
19.
Opt Express ; 31(4): 6062-6075, 2023 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-36823872

RESUMO

Optical image processing based on the photonic spin Hall effect (SHE) has been gaining significant attention as a convenient and an accurate way for image edge detection. However, the recent edge imaging techniques depending on optical differentiation is mainly achieved by modulation of one-dimensional photonic SHE. Here, we theoretically predict the two-dimensional photonic SHE in the anisotropic metamaterial, and find that its longitudinal and transverse displacements exhibit spin-dependent property at filling factors with increasing incidence angle. As the transverse and in-plane displacements induced by the photonic SHE can be controlled by the filling factor of the crystal structure, the optical axis angle, and the incident angle, this intrinsical effect can be used to realize a tunable edge imaging. Interestingly, by changing the optical axis of the anisotropic metamaterial, the in-plane displacements are equal to the transverse displacements for a certain filling factor and the corresponding incident angle. Therefore, we propose a two-dimensional image edge detection method based on the photonic SHE in anisotropic metamaterial. Further numerical results validate the theoretical proposal.

20.
Stem Cells ; 40(1): 88-101, 2022 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-35511860

RESUMO

Ovarian aging is a pacemaker with multiple organ dysfunction. Recently, stem cells with the ability to generate new oocytes have been identified, which provides the possibility of stem cell therapy for ovarian aging. Several studies have revealed the existence of stem cells in the human postmenopausal ovary. In this study, we describe a new method using magnetic-activated cell sorting combined with differential adhesion to isolate DDX4+ stem cells from ovaries of postmenopausal women and show that the cells exhibit similar gene expression profiles and growth characteristics with primitive germ cells. Furthermore, the DDX4+ stem cells could enter the meiosis stage and differentiation into oocytes. The RNA-seq data of the differentiated oocytes shows that mitochondrial metabolism may play an important role in the oogenesis process of the DDX4+ stem cells. Through using the human ovarian cortical fragments transplantation model, we indicated that the GFP-DDX4+ stem cells differentiated into some GFP positive oocyte-like structure in vivo. Our study provided a new method for the isolation of DDX4+ stem cells from the ovaries of postmenopausal women and confirmed the ability of these stem cells to differentiate into oocytes.


Assuntos
Ovário , Pós-Menopausa , Diferenciação Celular , Feminino , Células Germinativas , Humanos , Oócitos , Ovário/metabolismo , Células-Tronco/metabolismo
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