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1.
Hum Mol Genet ; 32(8): 1324-1333, 2023 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-36434787

RESUMO

The objective of this study was to discuss the mechanism of artesunate (ART) in improving cartilage damage in osteoarthritis (OA) by regulating the expression levels of metastatic tumor antigen 1 (MTA1), lipoxin A4 (LXA4) and the downstream JAK2/STAT3 signaling pathway. The OA model in vitro was constructed by stimulating chondrocytes for 24 h with 10 ng/mL interleukin (IL)-1ß, and cell proliferation and apoptosis, expression levels of Aggrecan, MTA1, LXA4, MMP3, MMP13 and Collagen II, and inflammatory cytokines in the culture supernatants were examined. Histopathological changes, inflammatory response and chondrocyte apoptosis of the cartilage tissues of OA mice were performed. In vitro cell experiments, ART enhanced cell proliferation capacity, accompanied by decreased apoptosis rate, decreased expression of MMP-3 and MMP-13, elevated expression of Collagen II and Aggrecan, as well as reduced levels of IL-6 and TNF-α in the cell supernatant. ART also ameliorated IL-1ß-induced chondrocyte damage by upregulating MTA1. The LXA4 promoter region had two potential binding sites for MTA1. There was a positive correlation between MTA1 and LXA4. MTA1 enhanced the expression of LXA4 through transcription and blocked the activation of the JAK2/STAT3 signaling pathway. In vivo animal model experiments further showed that ART treatment alleviated cartilage tissue damage in OA model mice by upregulating MTA1. Our study demonstrates that ART improves the cartilage damage of OA by upregulating MTA1 expression and promoting the transcriptional activation of LXA4, and further blocking the JAK2/STAT3 signaling pathway.


Assuntos
Neoplasias , Osteoartrite , Camundongos , Animais , Artesunato/metabolismo , Ativação Transcricional , Agrecanas/metabolismo , Cartilagem/metabolismo , Condrócitos/metabolismo , Osteoartrite/patologia , Transdução de Sinais , Colágeno/metabolismo , Neoplasias/patologia , Interleucina-1beta/metabolismo
2.
FASEB J ; 38(13): e23760, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38924449

RESUMO

Hyponatremia is the most common disorder of electrolyte imbalances. It is necessary to develop new type of diuretics to treat hyponatremia without losing electrolytes. Urea transporters (UT) play an important role in the urine concentrating process and have been proved as a novel diuretic target. In this study, rat and mouse syndromes of inappropriate antidiuretic hormone secretion (SIADH) models were constructed and analyzed to determine if UTs are a promising drug target for treating hyponatremia. Experimental results showed that 100 mg/kg UT inhibitor 25a significantly increased serum osmolality (from 249.83 ± 5.95 to 294.33 ± 3.90 mOsm/kg) and serum sodium (from 114 ± 2.07 to 136.67 ± 3.82 mmol/L) respectively in hyponatremia rats by diuresis. Serum chemical examination showed that 25a neither caused another electrolyte imbalance nor influenced the lipid metabolism. Using UT-A1 and UT-B knockout mouse SIADH model, it was found that serum osmolality and serum sodium were lowered much less in UT-A1 knockout mice than in UT-B knockout mice, which suggest UT-A1 is a better therapeutic target than UT-B to treat hyponatremia. This study provides a proof of concept that UT-A1 is a diuretic target for SIADH-induced hyponatremia and UT-A1 inhibitors might be developed into new diuretics to treat hyponatremia.


Assuntos
Hiponatremia , Síndrome de Secreção Inadequada de HAD , Proteínas de Membrana Transportadoras , Camundongos Knockout , Transportadores de Ureia , Animais , Masculino , Camundongos , Ratos , Modelos Animais de Doenças , Diuréticos/farmacologia , Hiponatremia/tratamento farmacológico , Hiponatremia/metabolismo , Síndrome de Secreção Inadequada de HAD/tratamento farmacológico , Síndrome de Secreção Inadequada de HAD/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Camundongos Endogâmicos C57BL , Concentração Osmolar , Ratos Sprague-Dawley , Sódio/metabolismo
3.
Chem Rev ; 123(8): 4795-4854, 2023 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-36921251

RESUMO

Carbon allotropes have contributed to all aspects of people's lives throughout human history. As emerging carbon-based low-dimensional materials, graphyne family members (GYF), represented by graphdiyne, have a wide range potential applications due to their superior physical and chemical properties. In particular, graphdiyne (GDY), as the leader of the graphyne family, has been practically applied to various research fields since it was first successfully synthesized. GYF have a large surface area, both sp and sp2 hybridization, and a certain band gap, which was considered to originate from the overlap of carbon 2pz orbitals and the inhomogeneous π-bonds of carbon atoms in different hybridization forms. These properties mean GYF-based materials still have many potential applications to be developed, especially in energy storage and catalytic utilization. Since most of the GYF have yet to be synthesized and applications of successfully synthesized GYF have not been developed for a long time, theoretical results in various application fields should be shared to experimentalists to attract more intentions. In this Review, we summarized and discussed the synthesis, structural properties, and applications of GYF-based materials from the theoretical insights, hoping to provide different viewpoints and comments.

4.
Mol Ther ; 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-39086131

RESUMO

Chimeric antigen receptor (CAR) T cells have shown significant efficacy in hematological diseases. However, CAR T therapy has demonstrated limited efficacy in solid tumors, including glioblastoma (GBM). One of the most important reasons is the immunosuppressive tumor microenvironment (TME), which promotes tumor growth and suppresses immune cells to eliminate tumor cells. The human transforming growth factor-beta (TGF-ß) plays a crucial role in forming the suppressive GBM TME and driving the suppression of the anti-GBM response. In order to mitigate TGF-ß mediated suppressive activity, we combined a dominant-negative TGF-ß receptor II (dnTGFßRII) with our previous bicistronic CART-EGFR-IL13Rα2 construct, currently being evaluated in a clinical trial, to generate CART-EGFR-IL13Rα2-dnTGFßRII, a tri-modular construct we are developing for clinical application. We hypothesized that this approach would more effectively subvert resistance mechanisms observed with GBM. Our data suggest that CART-EGFR-IL13Rα2-dnTGFßRII significantly augments T cell proliferation, enhances functional responses, and improves the fitness of bystander cells, particularly by decreasing the TGF-ß concentration in a TGF-ß-rich TME. Additionally, in vivo studies validated the safety and efficacy of the dnTGFßRII cooperating with CARs in targeting and eradicating GBM in a NSG mouse model.

5.
Mol Genet Genomics ; 299(1): 53, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38753163

RESUMO

SoxB subfamily is an important branch of Sox family and plays a key role in animal physiological process, but little is known about their function in planarian regeneration. This study aims to evaluate the function of DjSoxB family genes in intact and regenerating planarians Dugesia japonica. Here, we amplify the full-length cDNA of DjSoxB1 and DjSoxB2 in D. japonica by rapid amplification of the cDNA ends (RACE), detect the expression of DjSoxB family genes in planarian. The results show that DjSoxBs are expressed in parenchymal tissue and the hybridization signals partially disappear after irradiation indicates DjSoxB family genes are expressed in neoblasts. After the RNA interference (RNAi) of DjSoxB1, DjSoxB2 and DjSoxB3 separately, the numbers of proliferative cells are all reduced that causes planarians show slower growth of blastema in the early stage of regeneration, and nerves of planarians are affected that the movement speed of planarians decreases in varying degrees. Specially, planarians in the DjSoxB3 RNAi group show shrinkage and twisting. Overall, this study reveals that DjSoxB family genes play a role in cell proliferation during regeneration. They also play an important role in the maintenance of normal nerve function and nerve regeneration. These results provide directions for the functional study of SoxB family genes and provide an important foundation for planarian regeneration.


Assuntos
Planárias , Regeneração , Animais , Planárias/genética , Planárias/fisiologia , Regeneração/genética , Interferência de RNA , Proliferação de Células/genética , Proteínas de Helminto/genética , Proteínas de Helminto/metabolismo , Fatores de Transcrição SOXB1/genética
6.
BMC Cardiovasc Disord ; 24(1): 401, 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39090590

RESUMO

BACKGROUND: Patients with atrial fibrillation (AF) often have coronary artery disease (CAD), but the biological link between them remains unclear. This study aims to explore the common pathogenesis of AF and CAD and identify common biomarkers. METHODS: Gene expression profiles for AF and stable CAD were downloaded from the Gene Expression Omnibus database. Overlapping genes related to both diseases were identified using weighted gene co-expression network analysis (WGCNA), followed by functional enrichment analysis. Hub genes were then identified using the machine learning algorithm. Immune cell infiltration and correlations with hub genes were explored, followed by drug predictions. Hub gene expression in AF and CAD patients was validated by real-time qPCR. RESULTS: We obtained 28 common overlapping genes in AF and stable CAD, mainly enriched in the PI3K-Akt, ECM-receptor interaction, and relaxin signaling pathway. Two hub genes, COL6A3 and FKBP10, were positively correlated with the abundance of MDSC, plasmacytoid dendritic cells, and regulatory T cells in AF and negatively correlated with the abundance of CD56dim natural killer cells in CAD. The AUCs of COL6A3 and FKBP10 were all above or close to 0.7. Drug prediction suggested that collagenase clostridium histolyticum and ocriplasmin, which target COL6A3, may be potential drugs for AF and stable CAD. Additionally, COL6A3 and FKBP10 were upregulated in patients with AF and CAD. CONCLUSION: COL6A3 and FKBP10 may be key biomarkers for AF and CAD, providing new insights into the diagnosis and treatment of this disease.


Assuntos
Fibrilação Atrial , Doença da Artéria Coronariana , Bases de Dados Genéticas , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Aprendizado de Máquina , Transcriptoma , Humanos , Fibrilação Atrial/genética , Fibrilação Atrial/diagnóstico , Doença da Artéria Coronariana/genética , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/imunologia , Valor Preditivo dos Testes , Marcadores Genéticos , Biomarcadores/sangue , Masculino , Feminino
7.
J Nanobiotechnology ; 22(1): 241, 2024 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-38735933

RESUMO

BACKGROUND: Colorectal cancer (CRC) incidence is increasing in recent years due to intestinal flora imbalance, making oral probiotics a hotspot for research. However, numerous studies related to intestinal flora regulation ignore its internal mechanisms without in-depth research. RESULTS: Here, we developed a probiotic microgel delivery system (L.r@(SA-CS)2) through the layer-by-layer encapsulation technology of alginate (SA) and chitosan (CS) to improve gut microbiota dysbiosis and enhance anti-tumor therapeutic effect. Short chain fatty acids (SCFAs) produced by L.r have direct anti-tumor effects. Additionally, it reduces harmful bacteria such as Proteobacteria and Fusobacteriota, and through bacteria mutualophy increases beneficial bacteria such as Bacteroidota and Firmicutes which produce butyric acid. By binding to the G protein-coupled receptor 109A (GPR109A) on the surface of colonic epithelial cells, butyric acid can induce apoptosis in abnormal cells. Due to the low expression of GPR109A in colon cancer cells, MK-6892 (MK) can be used to stimulate GPR109A. With increased production of butyrate, activated GPR109A is able to bind more butyrate, which further promotes apoptosis of cancer cells and triggers an antitumor response. CONCLUSION: It appears that the oral administration of L.r@(SA-CS)2 microgels may provide a treatment option for CRC by modifying the gut microbiota.


Assuntos
Ácidos Graxos Voláteis , Microbioma Gastrointestinal , Limosilactobacillus reuteri , Probióticos , Microbioma Gastrointestinal/efeitos dos fármacos , Probióticos/farmacologia , Humanos , Ácidos Graxos Voláteis/metabolismo , Animais , Limosilactobacillus reuteri/metabolismo , Camundongos , Quitosana/química , Alginatos/química , Alginatos/farmacologia , Apoptose/efeitos dos fármacos , Antineoplásicos/farmacologia , Antineoplásicos/química , Administração Oral , Neoplasias Colorretais/tratamento farmacológico , Linhagem Celular Tumoral , Receptores Acoplados a Proteínas G/metabolismo , Microgéis/química , Camundongos Endogâmicos BALB C , Ácido Butírico/farmacologia , Ácido Butírico/metabolismo
8.
BMC Urol ; 24(1): 91, 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38643096

RESUMO

BACKGROUND: Sleep quality may be related to benign prostatic hyperplasia (BPH), however causal associations have not been established. This study aimed to evaluate causal relationships between six sleep traits ([i] day time napping, [ii] daytime sleepiness, [iii] insomnia, [iv] long sleep duration, [v] short sleep duration, and [vi] sleep duration per hour) and BPH through a bidirectional Mendelian randomization (MR) study. METHODS: Genome-wide association summary statistics of sleep traits and BPH were downloaded from public databases. Inverse variance weighting (IVW) was used as the main approach for causal inference. For causal estimates identified by IVW, various sensitivity analyses were performed to assess the reliability of the results: (i) four additional MR methods to complement IVW; (ii) Cochran's Q test to assess heterogeneity; (iii) MR-Egger intercept test and MR-PRESSO global test to assess horizontal pleiotropy; and (iv) leave-one-out method to assess stability. RESULTS: Forward MR analyses indicated that genetically predicted insomnia symptom significantly increased BPH risk (OR = 1.267, 95% CI: 1.003-1.601, P = 0.048), while reverse MR analyses identified that genetically predicted liability to BPH significantly increased the incidence of insomnia (OR = 1.026, 95% CI: 1.000-1.052, P = 0.048). In a replicate MR analysis based on summary statistics including exclusively male participants, the finding of increased risk of BPH due to genetically predicted insomnia symptom was further validated (OR = 1.488, 95% CI: 1.096-2.022, P = 0.011). No further causal links were identified. In addition, sensitivity tests demonstrated the reliability of the MR results. CONCLUSION: This study identified that a higher prevalence of genetically predicted insomnia symptoms may significantly increase the risk of BPH, while genetically predicted liability to BPH may in turn increase the incidence of insomnia symptom. Therefore, improving sleep quality and reducing the risk of insomnia could be a crucial approach for the prevention of BPH.


Assuntos
Hiperplasia Prostática , Distúrbios do Início e da Manutenção do Sono , Humanos , Masculino , Distúrbios do Início e da Manutenção do Sono/genética , Hiperplasia Prostática/complicações , Hiperplasia Prostática/genética , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Reprodutibilidade dos Testes
9.
Opt Express ; 31(5): 7321-7335, 2023 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-36859866

RESUMO

Tamm plasmon polaritons (TPPs) arise from electromagnetic resonant phenomena which appear at the interface between a metallic film and a distributed Bragg reflector. They differ from surface plasmon polaritons (SPPs), since TPPs possess both cavity mode properties and surface plasmon characteristics. In this paper, the propagation properties of TPPs are carefully investigated. With the aid of nanoantenna couplers, polarization-controlled TPP waves can propagate directionally. By combining nanoantenna couplers with Fresnel zone plates, asymmetric double focusing of TPP wave is observed. Moreover, radial unidirectional coupling of the TPP wave can be achieved when the nanoantenna couplers are arranged along a circular or a spiral shape, which shows superior focusing ability compared to a single circular or spiral groove since the electric field intensity at the focal point is 4 times larger. In comparison with SPPs, TPPs possess higher excitation efficiency and lower propagation loss. The numerical investigation shows that TPP waves have great potential in integrated photonics and on-chip devices.

10.
Acta Pharmacol Sin ; 44(2): 406-420, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35906293

RESUMO

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease. Cyst development in ADPKD involves abnormal epithelial cell proliferation, which is affected by the primary cilia-mediated signal transduction in the epithelial cells. Thus, primary cilium has been considered as a therapeutic target for ADPKD. Since ADPKD exhibits many pathological features similar to solid tumors, we investigated whether targeting primary cilia using anti-tumor agents could alleviate the development of ADPKD. Twenty-four natural compounds with anti-tumor activity were screened in MDCK cyst model, and 1-Indanone displayed notable inhibition on renal cyst growth without cytotoxicity. This compound also inhibited cyst development in embryonic kidney cyst model. In neonatal kidney-specific Pkd1 knockout mice, 1-Indanone remarkably slowed down kidney enlargement and cyst expansion. Furthermore, we demonstrated that 1-Indanone inhibited the abnormal elongation of cystic epithelial cilia by promoting tubulin polymerization and significantly down-regulating expression of anterograde transport motor protein KIF3A and IFT88. Moreover, we found that 1-Indanone significantly down-regulated ciliary coordinated Wnt/ß-catenin, Hedgehog signaling pathways. These results demonstrate that 1-Indanone inhibits cystic cell proliferation by reducing abnormally prolonged cilia length in cystic epithelial cells, suggesting that 1-Indanone may hold therapeutic potential to retard cyst development in ADPKD.


Assuntos
Cistos , Rim Policístico Autossômico Dominante , Camundongos , Animais , Rim Policístico Autossômico Dominante/tratamento farmacológico , Rim Policístico Autossômico Dominante/metabolismo , Rim Policístico Autossômico Dominante/patologia , Cílios , Tubulina (Proteína)/metabolismo , Proteínas Hedgehog/metabolismo , Rim/patologia , Camundongos Knockout , Cistos/metabolismo , Cistos/patologia , Canais de Cátion TRPP/metabolismo , Células Epiteliais/metabolismo
11.
Cereb Cortex ; 32(21): 4857-4868, 2022 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-35078209

RESUMO

Mild cognitive impairment in Parkinson's disease (PD-M) is related to a high risk of dementia. This study explored the whole-brain functional networks in early-stage PD-M. Forty-one patients with PD classified as cognitively normal (PD-N, n = 17) and PD-M (n = 24) and 24 demographically matched healthy controls (HC) underwent clinical and neuropsychological evaluations and resting-state functional magnetic resonance imaging. The global, regional, and modular topological characteristics were assessed in the brain functional networks, and their relationships to cognitive scores were tested. At the global level, PD-M and PD-N exhibited higher characteristic path length and lower clustering coefficient, local and global efficiency relative to HC. At the regional level, PD-M and PD-N showed lower nodal centrality in sensorimotor regions relative to HC. At the modular level, PD-M showed lower intramodular connectivity in default mode and cerebellum modules, and lower intermodular connectivity between default mode and frontoparietal modules than PD-N, correlated with Montreal Cognitive Assessment scores. Early-stage PD patients showed weaker small-worldization of brain networks. Modular connectivity alterations were mainly observed in patients with PD-M. These findings highlight the shared and distinct brain functional network dysfunctions in PD-M and PD-N, and yield insight into the neurobiology of cognitive decline in PD.


Assuntos
Disfunção Cognitiva , Doença de Parkinson , Humanos , Disfunção Cognitiva/patologia , Encéfalo , Imageamento por Ressonância Magnética , Mapeamento Encefálico
12.
Appl Microbiol Biotechnol ; 107(7-8): 2671-2688, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36864204

RESUMO

Recently, endorhizospheric microbiota is realized to be able to promote the secondary metabolism in medicinal plants, but the detailed metabolic regulation metabolisms and whether the promotion is influenced by environmental factors are unclear yet. Here, the major flavonoids and endophytic bacterial communities in various Glycyrrhiza uralensis Fisch. roots collected from seven distinct places in northwest China, as well as the edaphic conditions, were characterized and analyzed. It was found that the soil moisture and temperature might modulate the secondary metabolism in G. uralensis roots partially through some endophytes. One rationally isolated endophyte Rhizobium rhizolycopersici GUH21 was proved to promote the accumulation of isoliquiritin and glycyrrhizic acid significantly in roots of the potted G. uralensis under the relatively high-level watering and low temperature. Furthermore, we did the comparative transcriptome analysis of G. uralensis seedling roots in different treatments to investigate the detailed mechanisms of the environment-endophyte-plant interactions and found that the low temperature went hand in hand with the high-level watering to activate the aglycone biosynthesis in G. uralensis, while GUH21 and the high-level watering cooperatively promoted the in planta glucosyl unit production. Our study is of significance for the development of methods to rationally promote the medicinal plant quality. KEY POINTS: • Soil temperature and moisture related to isoliquiritin contents in Glycyrrhiza uralensis Fisch. • Soil temperature and moisture related to the hosts' endophytic bacterial community structures. • The causal relation among abiotic factors-endophytes-host was proved through the pot experiment.


Assuntos
Flavonas , Glycyrrhiza uralensis , Plantas Medicinais , Glycyrrhiza uralensis/química , Glycyrrhiza uralensis/metabolismo , Glycyrrhiza uralensis/microbiologia , Endófitos , Terpenos/metabolismo , Glicosídeos/metabolismo , Raízes de Plantas/microbiologia
13.
Mol Ther ; 30(7): 2537-2553, 2022 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-35570396

RESUMO

Bispecific T cell engagers (BiTEs) are bispecific antibodies that redirect T cells to target antigen-expressing tumors. We hypothesized that BiTE-secreting T cells could be a valuable therapy in solid tumors, with distinct properties in mono- or multi-valent strategies incorporating chimeric antigen receptor (CAR) T cells. Glioblastomas represent a good model for solid tumor heterogeneity, representing a significant therapeutic challenge. We detected expression of tumor-associated epidermal growth factor receptor (EGFR), EGFR variant III, and interleukin-13 receptor alpha 2 (IL13Rα2) on glioma tissues and cancer stem cells. These antigens formed the basis of a multivalent approach, using a conformation-specific tumor-related EGFR targeting antibody (806) and Hu08, an IL13Rα2-targeting antibody, as the single chain variable fragments to generate new BiTE molecules. Compared with CAR T cells, BiTE T cells demonstrated prominent activation, cytokine production, and cytotoxicity in response to target-positive gliomas. Superior response activity was also demonstrated in BiTE-secreting bivalent T cells compared with bivalent CAR T cells in a glioma mouse model at early phase, but not in the long term. In summary, BiTEs secreted by mono- or multi-valent T cells have potent anti-tumor activity in vitro and in vivo with significant sensitivity and specificity, demonstrating a promising strategy in solid tumor therapy.


Assuntos
Glioblastoma , Subunidade alfa2 de Receptor de Interleucina-13 , Animais , Linhagem Celular Tumoral , Receptores ErbB/genética , Receptores ErbB/metabolismo , Glioblastoma/patologia , Imunoterapia Adotiva , Camundongos , Linfócitos T , Ensaios Antitumorais Modelo de Xenoenxerto
14.
Antonie Van Leeuwenhoek ; 116(5): 487-497, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36905561

RESUMO

A Gram-stain-negative, aerobic, non-motile and rod-shaped strain, designated LJY008T, was isolated from the intestinal of Eriocheir sinensis in Pukou base of Jiangsu Institute of Freshwater Fisheries. Strain LJY008T could grow at 4-37 â„ƒ (optimum, 30 â„ƒ), pH 6.0-8.0 (optimum, pH 7.0), and with 1.0-6.0% NaCl (w/v; optimum, 1.0%). Strain LJY008T shared highest 16S rRNA gene sequence similarity with Jinshanibacter zhutongyuii CF-458T (99.3%), followed by J. allomyrinae BWR-B9T (99.2%), Insectihabitans xujianqingii CF-1111T (97.3%), and Limnobaculum parvum HYN0051T (96.7%). The major polar lipids include phosphatidylethanolamine, phosphatidylglycerol, and diphosphatidylglycerol. The only respiratory quinone was Q8, and the main fatty acids (> 10%) were C16:0, summed feature 3 (C16:1ω7c/C16:1ω6c), summed feature 8 (C18:1ω7c), and C14:0. The genome-based phylogenies showed that strain LJY008T was closely associated with members of the genus Jinshanibacter, Insectihabitans, and Limnobaculum. The average nucleotide identities and average amino acid identities (AAI) among strain LJY008T and closely related neighbours were all below 95%, and the digital DNA-DNA hybridization values among them were all below 36%. The genomic DNA G + C content of strain LJY008T was 46.1%. Based on the phenotypic, phylogenetic, biochemical and chemotaxonomic analysis, strain LJY008T represents a novel species of the genus Limnobaculum, for which the name Limnobaculum eriocheiris sp. nov. is proposed. The type strain is LJY008T (= JCM 34675T = GDMCC 1.2436T = MCCC 1K06016T). In addition, the genera Jinshanibacter and Insectihabitans were reclassified as Limnobaculum, because there was no significant genome-scale divergence or diagnosable difference on phenotypic and chemotaxonomic traits, such as strains of Jinshanibacter and Insectihabitans sharing AAI values of 93.88-94.96%.


Assuntos
Fosfolipídeos , Ubiquinona , Fosfolipídeos/análise , Filogenia , RNA Ribossômico 16S/genética , Ubiquinona/química , DNA Bacteriano/genética , Técnicas de Tipagem Bacteriana , Ácidos Graxos/análise , Análise de Sequência de DNA
15.
Lipids Health Dis ; 22(1): 155, 2023 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-37736681

RESUMO

BACKGROUND: Alzheimer's disease (AD) represents profound degenerative conditions of the brain that cause significant deterioration in memory and cognitive function. Despite extensive research on the significant contribution of lipid metabolism to AD progression, the precise mechanisms remain incompletely understood. Hence, this study aimed to identify key differentially expressed lipid metabolism-related genes (DELMRGs) in AD progression. METHODS: Comprehensive analyses were performed to determine key DELMRGs in AD compared to controls in GSE122063 dataset from Gene Expression Omnibus. Additionally, the ssGSEA algorithm was utilized for estimating immune cell levels. Subsequently, correlations between key DELMRGs and each immune cell were calculated specifically in AD samples. The key DELMRGs expression levels were validated via two external datasets. Furthermore, gene set enrichment analysis (GSEA) was utilized for deriving associated pathways of key DELMRGs. Additionally, miRNA-TF regulatory networks of the key DELMRGs were constructed using the miRDB, NetworkAnalyst 3.0, and Cytoscape software. Finally, based on key DELMRGs, AD samples were further segmented into two subclusters via consensus clustering, and immune cell patterns and pathway differences between the two subclusters were examined. RESULTS: Seventy up-regulated and 100 down-regulated DELMRGs were identified. Subsequently, three key DELMRGs (DLD, PLPP2, and PLAAT4) were determined utilizing three algorithms [(i) LASSO, (ii) SVM-RFE, and (iii) random forest]. Specifically, PLPP2 and PLAAT4 were up-regulated, while DLD exhibited downregulation in AD cerebral cortex tissue. This was validated in two separate external datasets (GSE132903 and GSE33000). The AD group exhibited significantly altered immune cell composition compared to controls. In addition, GSEA identified various pathways commonly associated with three key DELMRGs. Moreover, the regulatory network of miRNA-TF for key DELMRGs was established. Finally, significant differences in immune cell levels and several pathways were identified between the two subclusters. CONCLUSION: This study identified DLD, PLPP2, and PLAAT4 as key DELMRGs in AD progression, providing novel insights for AD prevention/treatment.


Assuntos
Doença de Alzheimer , MicroRNAs , Humanos , Doença de Alzheimer/genética , Metabolismo dos Lipídeos/genética , Algoritmos , Encéfalo , MicroRNAs/genética
16.
Adv Exp Med Biol ; 1398: 281-287, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36717501

RESUMO

One of the most prevalent indications of water-electrolyte imbalance is edema. Aquaporins (AQPs) are a protein family that can function as water channels. Osmoregulation and body water homeostasis are dependent on the regulation of AQPs. Human kidneys contain nine AQPs, five of which have been demonstrated to have a role in body water balance: AQP1, AQP2, AQP3, AQP4, and AQP7. Water imbalance is connected with AQP dysfunction. Hyponatremia with elevated AQP levels can accompany edema, which can be caused by disorders with low effective circulating blood volume and systemic vasodilation, such as congestive heart failure (CHF), hepatic cirrhosis, or the syndrome of incorrect antidiuretic hormone secretion (SIADH). In CHF, upregulation of AQP2 expression and targeting is critical for water retention. AQP2 is also involved in aberrant water retention and the formation of ascites in cirrhosis of the liver. Furthermore, water retention and hyponatremia in SIADH are caused by increased expression of AQP2 in the collecting duct. Fluid restriction, demeclocycline, and vasopressin type-2 receptor antagonists are widely utilized to treat edema. The relationship between AQPs and edema is discussed in this chapter.


Assuntos
Aquaporinas , Insuficiência Cardíaca , Hiponatremia , Síndrome de Secreção Inadequada de HAD , Humanos , Aquaporina 2/genética , Síndrome de Secreção Inadequada de HAD/metabolismo , Hiponatremia/metabolismo , Aquaporinas/genética , Aquaporinas/metabolismo , Edema , Água/metabolismo
17.
Anim Biotechnol ; 34(9): 4947-4956, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37204073

RESUMO

Thermostatic animals need to maintain a stable body temperature. A high-temperature environment can cause body temperature to exceed the range of tolerance of the organism, resulting in a heat stress response. The reproductive organs (such as the testes) are more sensitive to temperature due to their special anatomical location. However, to date, the effect of heat stress on the biological function of insulin in testicular cells has not been revealed. Therefore, the current study established a testis cell model to study the effect of heat stress on the biological activity of insulin. The results showed significant alterations in the insulin-induced intracellular signaling under heat stress conditions. Moreover, the IR-mediated intracellular signaling pathway was significantly downregulated under heat stress conditions. Further studies demonstrated that heat stress led to senescence of testicular cells by Sa-ß-gal staining. Furthermore, the expression of senescence markers (p16 and p21) was increased under heat stress. In addition, heat stress was found to cause oxidative stress in testicular cells, which may be the underlying molecular mechanism by which heat stress changes the signaling properties of insulin. Collectively, the current study showed that heat stress caused alterations in insulin-induced intracellular signaling. Heat stress also induced testicular cell senescence.


Assuntos
Insulinas , Testículo , Masculino , Animais , Suínos , Testículo/metabolismo , Senescência Celular/fisiologia , Estresse Oxidativo , Resposta ao Choque Térmico , Insulinas/metabolismo , Insulinas/farmacologia
18.
J Craniofac Surg ; 34(6): e568-e572, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37246294

RESUMO

OBJECTIVE: To look into the association between the degree of deviation and the changing trend in the temporomandibular joint (TMJ) space volume after orthognathic surgery in patients with skeletal Class III malocclusion. METHODS: Twenty patients having combined orthodontic-orthognathic treatment for skeletal Class III malocclusions with mandibular deviation were chosen, and craniofacial spiral CT was performed before (T0), two weeks after (T1), and six months after (T2) surgery. Using 3D volume reconstruction, further partitioning, and analysis of each domain's volume changes over time, the TMJ space volume is to be obtained. The differences in changes between groups A (mild deviation group) and B (severe deviation group) were examined to examine the impact of the degree of deviation on the TMJ space volume. RESULTS: A statistically significant difference ( P <0.05) existed between the postoperative TMJ space volume in group A and the preoperative overall, anterolateral, and anteroinferior space volume; the same difference also existed between the postoperative TMJ space volume in the NDS and the preoperative posterolateral, posteroinferior space volume. In group B, the postoperative TMJ space volume was statistically significant ( P <0.05) compared with the preoperative total and anteroinferior space volume in the DS; the difference between the total volume of the T1 stage on the NDS and the total volume of the T0 stage was statistically significant ( P <0.05). The two groups showed substantial differences in the space volume changes between the T1-T0 phase and the T2-T1 period. CONCLUSION: Patients with skeletal Class III malocclusion and mandibular deviation after orthognathic surgery see a change in the TMJ space volume. All patient types experience a largely consistent space volume change trend two weeks after surgery, and the degree of mandibular deviation is correlated with the intensity and longevity of the alteration.


Assuntos
Má Oclusão Classe III de Angle , Má Oclusão , Cirurgia Ortognática , Procedimentos Cirúrgicos Ortognáticos , Humanos , Imageamento Tridimensional , Má Oclusão/cirurgia , Articulação Temporomandibular/diagnóstico por imagem , Articulação Temporomandibular/cirurgia , Má Oclusão Classe III de Angle/diagnóstico por imagem , Má Oclusão Classe III de Angle/cirurgia , Mandíbula/diagnóstico por imagem , Mandíbula/cirurgia
19.
Sensors (Basel) ; 23(6)2023 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-36991634

RESUMO

Few-shot semantic segmentation has attracted much attention because it requires only a few labeled samples to achieve good segmentation performance. However, existing methods still suffer from insufficient contextual information and unsatisfactory edge segmentation results. To overcome these two issues, this paper proposes a multi-scale context enhancement and edge-assisted network (called MCEENet) for few-shot semantic segmentation. First, rich support and query image features were extracted, respectively, using two weight-shared feature extraction networks, each consisting of a ResNet and a Vision Transformer. Subsequently, a multi-scale context enhancement (MCE) module was proposed to fuse the features of ResNet and Vision Transformer, and further mine the contextual information of the image by using cross-scale feature fusion and multi-scale dilated convolutions. Furthermore, we designed an Edge-Assisted Segmentation (EAS) module, which fuses the shallow ResNet features of the query image and the edge features computed by the Sobel operator to assist in the final segmentation task. We experimented on the PASCAL-5i dataset to demonstrate the effectiveness of MCEENet; the results of the 1-shot setting and 5-shot setting on the PASCAL-5i dataset are 63.5% and 64.7%, which surpasses the state-of-the-art results by 1.4% and 0.6%, respectively.

20.
Int J Mol Sci ; 24(3)2023 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-36768248

RESUMO

Tissue phenotypic plasticity facilitates rapid adaptation of organisms to biotic and/or abiotic pressure. The reproductive capacity of honey bee workers (Apis mellifera) is plastic and responsive to pheromones produced by broods and the queen. Egg laying workers (ELWs), which could reactivate their ovaries and lay haploid eggs upon queen lost, have been commonly discussed from many aspects. However, it remains unclear whether midgut homeostasis in ELWs is affected during plastic changes. Here, we found that the expression of nutrition- and autophagy-related genes was up-regulated in the midguts of ELWs, compared with that in nurse workers (NWs) by RNA-sequencing. Furthermore, the area and number of autophagosomes were increased, along with significantly increased cell death in the midguts of ELWs. Moreover, cell cycle progression in the midguts of ELWs was increased compared with that in NWs. Consistent with the up-regulation of nutrition-related genes, the body and midgut sizes, and the number of intestinal proliferation cells of larvae reared with royal jelly (RJ) obviously increased more than those reared without RJ in vitro. Finally, cell proliferation was dramatically suppressed in the midguts of ELWs when autophagy was inhibited. Altogether, our data suggested that autophagy was induced and required to sustain cell proliferation in ELWs' midguts, thereby revealing the critical role of autophagy played in the intestines during phenotypic plasticity changes.


Assuntos
Autofagia , Intestinos , Abelhas/genética , Animais , Larva/fisiologia , Autofagia/genética , Adaptação Fisiológica , Proliferação de Células
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