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1.
Front Med (Lausanne) ; 11: 1441196, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39351004

RESUMO

Purpose: To analyze the therapeutic effect and mechanism of Urolithin A (UA) on delayed corneal epithelial wound healing. Methods: The C57BL/6 mice were continuously exposed to hyperosmotic stress (HS) for 7 days followed by the removal of central corneal epithelium to establish a delayed corneal epithelial wound healing model in vivo. In vitro, the human corneal epithelial cell line (HCE-T) was also incubated under HS. UA was administered in vivo and in vitro to study its effects on corneal epithelial cells. Senescence-associated ß-galactosidase (SA-ß-gal) staining was performed to detect the level of cell senescence. Transcriptome sequencing (RNA-seq) was conducted to elucidate the molecular mechanism underlying the effect of UA on corneal epithelial repair. Additionally, the expression of senescence-related and ferroptosis-related genes and the levels of lipid peroxides (LPO) and malondialdehyde (MDA) were measured. Results: Hyperosmotic stress (HS) significantly increased the proportion of SA-ß-gal staining positive cells in corneal epithelial cells and upregulated the expression of p16 and p21 (p < 0.0001). Topical application of UA decreased the accumulation of senescent cells in corneal epithelial wounds and promoted epithelial wound healing. The results of RNA-seq of HS-induced corneal epithelial cells showed that the ferroptosis pathway was significantly dysregulated. Further investigation revealed that UA decreased the level of oxidative stress in HCE-T cells, including the levels of LPO and MDA (p < 0.05). Inhibition of ferroptosis significantly prevented cellular senescence in HS-induced HCE-T cells. Conclusion: In this study, UA promoted HS-induced delayed epithelial wound healing by reducing the senescence of corneal epithelial cells through the inhibition of ferroptosis.

2.
RSC Med Chem ; 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39345717

RESUMO

A smart dendritic cell (DC)-derived whole cell cytokine (DWC) nano-regulator of TCPs was developed for tumor cytokine-immunotherapy. The DWCs were purified from activated DC-cultured media and applied as a nano-dosage form. It was found that TCPs could remodel extracellular matrices via the elimination of fibronectin and type I collagen (Col-I) in tumor tissues, as well as the inhibition of α-SMA expression in cancer associated fibroblasts (CAFs). Furthermore, after local TCP treatment, significant tumor inhibition could be achieved combined with radiotherapy.

3.
Microbiol Spectr ; 12(10): e0032524, 2024 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-39264158

RESUMO

Brain abscess is a severe infection characterized by the accumulation of pus within the brain parenchyma. Accurate identification of the causative pathogens is crucial for effective treatment and improved patient outcomes. This 10-year retrospective, single-center study aimed to compare the detection performance of conventional culture methods and metagenomic next-generation sequencing (mNGS) in brain abscess. We reviewed 612 patients diagnosed with brain abscess and identified 174 cases with confirmed etiology. The median age was 52 years, with 69.5% males. Culture tests predominately identified gram-positive bacteria, particularly Streptococcus spp. Gram-negative bacteria, including Klebsiella spp., were also detected. However, mNGS revealed a more diverse pathogen spectrum, focusing on anaerobes (e.g., Fusobacterium spp., Parvimonas spp., Porphyromonas spp., Prevotella spp., and Tannerella spp.). mNGS exhibited significantly higher overall pathogen-positive rates in pus samples (85.0% vs 50.0%, P = 0.0181) and CSF samples (84.2% vs 7.9%, P < 0.0001) compared to culture. Furthermore, the detection rates for anaerobes displayed a notable disparity, with mNGS yielding significantly higher positive detections in both pus samples (50.0% vs 10%, P = 0.0058) and CSF samples (18.4% vs 0%, P = 0.0115) when compared to culture methods. The assistance of mNGS in pathogen detection, particularly anaerobes in brain abscess, was evident in our findings. mNGS demonstrated the ability to identify rare and fastidious pathogens, even in culture-negative cases. These results emphasize the clinical value of mNGS as a supplement for brain abscess, enabling more comprehensive and accurate pathogen identification.IMPORTANCEThe accurate identification of pathogens causing brain abscess is crucial for effective treatment and improved patient outcomes. In this 10-year retrospective study, the detection performance of conventional culture methods and metagenomic next-generation sequencing (mNGS) was compared. The study analyzed 612 patients with brain abscess and confirmed etiology in 174 cases. The results showed that culture tests predominantly identified gram-positive bacteria, while mNGS unveiled a broader diverse pathogen spectrum, particularly anaerobes. The mNGS method exhibited significantly higher overall rates of pathogen positivity both in pus and cerebrospinal fluid (CSF) samples, surpassing the culture methods. Notably, mNGS detected a significantly higher number of anaerobes in both pus and CSF samples compared to culture methods. These findings underscore the clinical value of mNGS as a supplement for brain abscess diagnosis, enabling more comprehensive and accurate pathogen identification, particularly for rare and fastidious pathogens that evade detection by conventional culture methods.


Assuntos
Abscesso Encefálico , Sequenciamento de Nucleotídeos em Larga Escala , Metagenômica , Humanos , Abscesso Encefálico/microbiologia , Abscesso Encefálico/diagnóstico , Estudos Retrospectivos , Masculino , Pessoa de Meia-Idade , Feminino , Metagenômica/métodos , Adulto , Idoso , Bactérias/isolamento & purificação , Bactérias/genética , Bactérias/classificação , Adulto Jovem , Adolescente , Bactérias Gram-Positivas/isolamento & purificação , Bactérias Gram-Positivas/genética , Bactérias Gram-Positivas/classificação , Bactérias Gram-Negativas/isolamento & purificação , Bactérias Gram-Negativas/genética , Bactérias Gram-Negativas/classificação
4.
Int J Mol Sci ; 25(18)2024 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-39337713

RESUMO

Glial-cell-line-derived neurotrophic factor (GDNF) is highly expressed and is involved in the malignant phenotype in glioblastomas (GBMs). However, uncovering its underlying mechanism for promoting GBM progression is still a challenging work. In this study, we found that serine protease inhibitor family E member 1 (SERPINE1) was a potential downstream gene of GDNF. Further experiments confirmed that SERPINE1 was highly expressed in GBM tissues and cells, and its levels of expression and secretion were enhanced by exogenous GDNF. SERPINE1 knockdown inhibited the migration and invasion of GBM cells promoted by GDNF. Mechanistically, GDNF increased SERPINE1 by promoting the phosphorylation of SMAD2/3. In vivo experiments demonstrated that GDNF facilitated GBM growth and the expressions of proteins related to migration and invasion via SERPINE1. Collectively, our findings revealed that GDNF upregulated SERPINE1 via the SMAD2/3-signaling pathway, thereby accelerating GBM cell migration and invasion. The present work presents a new mechanism of GDNF, supporting GBM development.


Assuntos
Movimento Celular , Fator Neurotrófico Derivado de Linhagem de Célula Glial , Glioblastoma , Invasividade Neoplásica , Inibidor 1 de Ativador de Plasminogênio , Transdução de Sinais , Animais , Humanos , Masculino , Camundongos , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Regulação Neoplásica da Expressão Gênica , Fator Neurotrófico Derivado de Linhagem de Célula Glial/metabolismo , Fator Neurotrófico Derivado de Linhagem de Célula Glial/genética , Glioblastoma/metabolismo , Glioblastoma/patologia , Glioblastoma/genética , Camundongos Nus , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Inibidor 1 de Ativador de Plasminogênio/genética , Proteína Smad2/metabolismo , Proteína Smad2/genética , Proteína Smad3/metabolismo , Proteína Smad3/genética
5.
Int J Urol ; 2024 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-39306731

RESUMO

OBJECTIVE: Folic acid is a commonly used dietary supplement of trace element, but it may increase the risk of prostate cancer (PCa). The aim of this study was to investigate the causal relationship between PCa and folic acid supplementation, as well as dietary folate equivalents, using Mendelian randomization (MR) analysis. METHODS: The Genome-Wide Association Study (GWAS) data of folic acid supplementation and dietary folate equivalents were selected from UK Biobank. Meta-analysis of GWASs of PCa was obtained from PCa Association Group to Investigate Cancer-Associated Alterations in the Genome consortium. MR analysis was performed with inverse variance weighted (IVW) method, MR-Egger regression, simple mode, weighted median, and weighted mode analysis. Heterogeneity and horizontal pleiotropy tests and reverse MR analysis were conducted to assess the robustness and reliability of the causal inference. RESULTS: Six single nucleotide polymorphisms (SNPs) associated with folic acid supplementation and five SNPs associated with dietary folate equivalents were identified as instrumental variables. Genetically predicted folic acid supplementation was associated with an increased risk of PCa (OR 1.200, p < 0.001, by IVW method), and there was no evidence of heterogeneity, horizontal pleiotropy, or significant reverse causality (all p > 0.05). In contrast, dietary folate equivalents showed no significant correlation with PCa (p > 0.05 for all five MR methods). CONCLUSION: This study demonstrated an association between increased risk of PCa and folic acid supplementation, but not with dietary folate equivalents. These findings have implications for public health interventions and personalized preventive strategies for PCa.

6.
iScience ; 27(9): 110606, 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39246443

RESUMO

The biological mechanisms underlying the development of myopia have not yet been completely elucidated. The retina is critical for visual signal processing, which primarily utilizes aerobic glycolysis to produce lactate as a metabolic end product. Lactate facilitates lysine lactylation (Kla), a posttranslational modification essential for transcriptional regulation. This study found increased glycolytic flux and lactate accumulation in the retinas of form-deprived myopic guinea pigs. Subsequently, a comprehensive analysis of Kla levels in retinal proteins revealed that Kla was upregulated at 124 sites in 92 proteins and downregulated at three sites in three proteins. Functional enrichment and protein interaction analyses showed significant enrichment in pathways related to energy metabolism, including glutathione metabolism, glycolysis, and the hypoxia-inducible factor-1 signaling pathway. Parallel-reaction monitoring confirmed data reliability. These findings suggest a connection between myopia and retinal energy metabolism imbalance, providing new insights into the pathogenesis of myopia.

7.
Sci Rep ; 14(1): 19211, 2024 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-39160341

RESUMO

Understanding the mechanical characteristics of rocks when subjected to direct tension is crucial for assessing the stability of rock formations. Within the scope of this research, a series of tests was conducted using Tage tuff to assess the deformation behavior and crack extension of rock under direct tension. The axial, lateral, and shear strain fields as well as crack propagation, localized deformation behavior, and failure mode of the rocks were analyzed using three-dimensional digital image correlation method. The results showed that the axial strain fields on the specimen surface were heterogeneous, with different locations and localization occurring in the pre-peak stage, which was similar to the evolution of shear strain, whereas the lateral strain only showed slight changes. The crack extension direction was inferred, indicating that both tensile and shear stress occurred in the tests. Furthermore, different stress-strain responses were observed for the inside and outside of the localized bands. Then, the surface patterns of specimen failure were scanned and analyzed to assess the failure mode and residual strength of the specimen under direct tensile stress. Finally, the results of direct tension, uniaxial compression, and Brazilian split tests for Tage tuff were compared, and the complete stress-strain curve of uniaxial tension (UT) was simulated using a nonlinear-variable-compliance constitutive equation. This study provides a deeper understanding into the damage behavior of rocks under direct tension.

8.
Int J Food Microbiol ; 425: 110848, 2024 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-39208563

RESUMO

Antimicrobial resistance represents a global health emergency, necessitating the introduction of novel antimicrobial agents. In the present study, lysozyme and holin from Shigella flexneri 1.1868 phage SGF2, named LysSGF2 and HolSGF2, respectively, were cloned, expressed, and characterized. LysSGF2 and HolSGF2 showed lytic activities against S. flexneri 1.1868 cells at 4-55 °C and pH 3.1-10.3. LysSGF2 exhibited antimicrobial activity against five gram-negative and two gram-positive bacteria. HolSGF2 showed antimicrobial activity against four gram-negative and one gram-positive species. The antibacterial activities of LysSGF2 and HolSGF2 were determined in liquid beverages, including bottled water and milk. The relative lytic activity of LysSGF2 combined with HolSGF2 against the tested bacteria was approximately 46-77 % in water. Furthermore, the combination markedly decreased the viable counts of tested bacteria by approximately 3-5 log CFU/mL. LysSGF2 and HolSGF2 could efficiently remove biofilms on polystyrene, glass, and stainless-steel. The efficacy of the LysSGF2 and HolSGF2 combination against the tested bacteria on polystyrene was 58-71 %. Combination treatment effectively killed biofilm cells formed on stainless-steel and glass by 1-4 log CFU/mL. ese results indicate that LysSGF2 and HolSGF2 can successfully control both the planktonic and biofilm cells of common pathogenic bacteria, suggesting that the combined or single use of LysSGF2 and HolSGF2 may be of great value in food processing.


Assuntos
Biofilmes , Biofilmes/efeitos dos fármacos , Bacteriófagos , Antibacterianos/farmacologia , Plâncton/efeitos dos fármacos , Shigella flexneri/efeitos dos fármacos , Muramidase/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Animais
9.
Brain Res ; 1845: 149199, 2024 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-39187054

RESUMO

Individuals with high social anxiety show a more considerable attentional bias toward self-relevant information and outwardly threatening stimuli than do those with low social anxiety. Some studies have investigated the attentional bias between self-relevant information and external social cues in people with high social anxiety but have not reached consistent conclusions. This study used a modified dot-probe task and collected temporal and electroencephalogram responses to three self-other face pairs among 15 people with high social anxiety and 20 people with low social anxiety. Both groups responded quicker to self-relevant information than external social cues. Others' emotional potencies moderated the attentional bias. Individuals with high social anxiety exhibited larger P1 amplitudes and smaller N170 amplitudes (mainly in the right hemisphere) for all face pairs and larger P2 amplitudes for the self-neutral and other-angry face pairs than those with low social anxiety. These findings suggest that people with social anxiety prioritize allocating attentional resources to self-relevant information, with others' angry faces having the greatest influence on the allocation. Individuals with high social anxiety initially exhibit more attentional vigilance and less structural coding for face pairs, followed by heightened engagement with threatening cues compared to those with low social anxiety.

10.
J Med Chem ; 67(16): 13604-13638, 2024 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-39080842

RESUMO

PRMT5, a type 2 arginine methyltransferase, has a critical role in regulating cell growth and survival in cancer. With the aim of developing MTA-cooperative PRMT5 inhibitors suitable for MTAP-deficient cancers, herein we report our efforts to develop novel "MTA-cooperative" compounds identified through a high-throughput biochemical screening approach. Optimization of hits was achieved through structure-based design with a focus on improvement of oral drug-like properties. Bioisosteric replacement of the original thiazole guanidine headgroup, spirocyclization of the isoindolinone amide scaffold to both configurationally and conformationally lock the bioactive form, and fine-tuning of the potency, MTA cooperativity, and DMPK properties through specific substitutions of the azaindole headgroup were conducted. We have identified an orally available in vivo lead compound, 28 ("AZ-PRMT5i-1"), which shows sub-10 nM PRMT5 cell potency, >50-fold MTA cooperativity, suitable DMPK properties for oral dosing, and significant PRMT5-driven in vivo efficacy in several MTAP-deficient preclinical cancer models.


Assuntos
Inibidores Enzimáticos , Proteína-Arginina N-Metiltransferases , Proteína-Arginina N-Metiltransferases/antagonistas & inibidores , Proteína-Arginina N-Metiltransferases/metabolismo , Humanos , Animais , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/síntese química , Relação Estrutura-Atividade , Camundongos , Descoberta de Drogas , Linhagem Celular Tumoral , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química
11.
Des Monomers Polym ; 27(1): 62-86, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39077753

RESUMO

Hyperbranched polyphosphate polyesters (HPPs) as a special class of hyperbranched polymers have attracted increased interest and have been intensively studied, because of peculiar structures, excellent biocompatibility, flexibility in physicochemical properties, biodegradability, water soluble, thermal stability, and mechanical properties. HPPs can be divided into phosphates as monomers and phosphates as end groups. In this article, the classification, general synthesis, modifications, and applications of HPP are reviewed. In addition, recent developments in the application of HPP are described, such as modified or functionalized by end capping and hypergrafting to improve the performances in polymer blends, coatings, flame retardant, leather. Furthermore, the modifications and application of HPPs in biomedical materials, such as drug delivery and bone regeneration were discussed. In summary, the hyperbranched polymer enlarges its application range and improves its application performance compared with conventional polymer. In the future, more new HPPs composite materials will be developed through hyperbranched technique. This review of HPPs will provide useful theoretical basis and technical support for the development of new hyperbranched polymer material.

12.
Orphanet J Rare Dis ; 19(1): 266, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39010060

RESUMO

BACKGROUND: The heart can be involved in immunoglobulin (Ig)-G4-related disease (IgG4-RD). This study aimed to summarize the clinical features and efficacy of treatment for IgG4-RD patients with heart involvement. METHODS: We conducted a retrospective study enrolling 42 IgG4-RD patients with heart involvement from the IgG4-RD cohorts of the Peking Union Medical College Hospital and Beijing An Zhen Hospital, from 2010 to 2022. Clinical, laboratory, radiological data were collected, and treatment responses to glucocorticoids and immunosuppressants were analyzed. RESULTS: IgG4-related cardiac involvement is a rare part of the IgG4-RD spectrum. The incidences of coronary periarteritis and pericarditis were 1.2%(13/1075) and 3.1%(33/1075), respectively in our cohort. Valvular disease possibly related to IgG4-RD was detected in two patients. None of the patients with myocardial involvement were identified. The average age was 58.2 ± 12.8 years, with a male predominance (76.7%). Coronary artery CT revealed that mass-like and diffuse wall-thickening lesions were the most frequently observed type of coronary periarteritis. Pericarditis presented as pericardial effusion, localized thickening, calcification and mass. After treatment with glucocorticoid and immunosuppressants, all patients achieved a reduced IgG4-RD responder index score and achieved radiological remission. Two patients with coronary peri-arteritis experienced clinical relapses during the maintenance period. CONCLUSIONS: Cardiac involvement in IgG4-RD is rare and easily overlooked since many patients are asymptomatic, and the diagnosis relies on imaging. Patients showed a satisfactory response to glucocorticoid based treatment.


Assuntos
Doença Relacionada a Imunoglobulina G4 , Pericardite , Humanos , Estudos Retrospectivos , Masculino , Pessoa de Meia-Idade , Pericardite/tratamento farmacológico , Pericardite/patologia , Pericardite/diagnóstico por imagem , Feminino , Doença Relacionada a Imunoglobulina G4/tratamento farmacológico , Doença Relacionada a Imunoglobulina G4/patologia , Idoso , Adulto , Arterite/tratamento farmacológico , Arterite/diagnóstico por imagem , Arterite/patologia , Imunoglobulina G , Estudos de Coortes , Glucocorticoides/uso terapêutico
13.
Exp Eye Res ; 245: 109953, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38838974

RESUMO

The objective of this study was to investigate the biological feasibility and surgical applicability of decellularized porcine small intestinal submucosa (DSIS) in conjunctiva reconstruction. A total of 52 Balb/c mice were included in the study. We obtained the DSIS by decellularization, evaluated the physical and biological properties of DSIS in vitro, and further evaluated the effect of surgical transplantation of DSIS scaffold in vivo. The histopathology and ultrastructural analysis results showed that the scaffold retained the integrity of the fibrous morphology while removing cells. Biomechanical analysis showed that the elongation at break of the DSIS (239.00 ± 12.51%) were better than that of natural mouse conjunctiva (170.70 ± 9.41%, P < 0.05). Moreover, in vivo experiments confirmed the excellent biocompatibility of the decellularized scaffolds. In the DSIS group, partial epithelialization occurred at day-3 after operation, and the conjunctival injury healed at day-7, which was significantly faster than that in human amniotic membrane (AM) and sham surgery (SHAM) group (P < 0.05). The number and distribution of goblet cells of transplanted DSIS were significantly better than those of the AM and SHAM groups. Consequently, the DSIS scaffold shows excellent biological characteristics and surgical applicability in the mouse conjunctival defect model, and DSIS is expected to be an alternative scaffold for conjunctival reconstruction.


Assuntos
Túnica Conjuntiva , Mucosa Intestinal , Intestino Delgado , Camundongos Endogâmicos BALB C , Engenharia Tecidual , Alicerces Teciduais , Animais , Camundongos , Túnica Conjuntiva/citologia , Suínos , Mucosa Intestinal/transplante , Mucosa Intestinal/citologia , Intestino Delgado/transplante , Engenharia Tecidual/métodos , Procedimentos de Cirurgia Plástica/métodos , Células Caliciformes/citologia , Modelos Animais de Doenças , Masculino
14.
J Med Chem ; 67(11): 8962-8987, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38748070

RESUMO

Dysregulation of histone methyl transferase nuclear receptor-binding SET domain 2 (NSD2) has been implicated in several hematological and solid malignancies. NSD2 is a large multidomain protein that carries histone writing and histone reading functions. To date, identifying inhibitors of the enzymatic activity of NSD2 has proven challenging in terms of potency and SET domain selectivity. Inhibition of the NSD2-PWWP1 domain using small molecules has been considered as an alternative approach to reduce NSD2-unregulated activity. In this article, we present novel computational chemistry approaches, encompassing free energy perturbation coupled to machine learning (FEP/ML) models as well as virtual screening (VS) activities, to identify high-affinity NSD2 PWWP1 binders. Through these activities, we have identified the most potent NSD2-PWWP1 binder reported so far in the literature: compound 34 (pIC50 = 8.2). The compounds identified herein represent useful tools for studying the role of PWWP1 domains for inhibition of human NSD2.


Assuntos
Desenho de Fármacos , Histona-Lisina N-Metiltransferase , Histona-Lisina N-Metiltransferase/antagonistas & inibidores , Histona-Lisina N-Metiltransferase/metabolismo , Histona-Lisina N-Metiltransferase/química , Ligantes , Humanos , Proteínas Repressoras/antagonistas & inibidores , Proteínas Repressoras/química , Proteínas Repressoras/metabolismo , Relação Estrutura-Atividade , Aprendizado de Máquina , Modelos Moleculares , Domínios Proteicos
15.
Int J Cardiol ; 404: 131970, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38490268

RESUMO

The crucial pathophysiological and prognostic roles of the right ventricle in various diseases have been well-established. Nonetheless, conventional cardiovascular imaging modalities are frequently associated with intrinsic limitations when evaluating right ventricular (RV) morphology and function. The integration of artificial intelligence (AI) in multimodality imaging presents a promising avenue to circumvent these obstacles, paving the way for future fully automated imaging paradigms. This review aimed to address the current challenges faced by clinicians and researchers in integrating RV imaging and AI technology, to provide a comprehensive overview of the current applications of AI in RV imaging, and to offer insights into future directions, opportunities, and potential challenges in this rapidly advancing field.


Assuntos
Inteligência Artificial , Ventrículos do Coração , Humanos , Ventrículos do Coração/diagnóstico por imagem , Imagem Multimodal , Cabeça
16.
Water Res ; 253: 121289, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38341975

RESUMO

Antibiotic resistance poses a significant threat to global health, and the microbe-rich activated sludge environment may contribute to the dissemination of antibiotic resistance genes (ARGs). ARGs spread across various bacterial populations via multiple dissemination routes, including horizontal gene transfer mediated by bacteriophages (phages). However, the potential role of phages in spreading ARGs in wastewater treatment systems remains unclear. This study characterized the core resistome, mobile genetic elements (MGEs), and virus-associated ARGs (vir_ARGs) in influents (Inf) and effluents (Eff) samples from nine WWTPs in eastern China. The abundance of ARGs in the Inf samples was higher than that in the Eff samples. A total of 21 core ARGs were identified, accounting for 38.70 %-83.70 % of the different samples. There was an increase in MGEs associated with phage-related processes from influents to effluents (from 12.68 % to 21.10 %). These MGEs showed strong correlations in relative abundance and composition with the core ARGs in the Eff samples. Across the Inf and Eff samples, 58 unique vir_ARGs were detected, with the Eff samples exhibiting higher diversity of vir_ARGs than the Inf samples. Statistical analyses indicated a robust relationship between core ARG profile, MGEs associated with phage-related processes, and vir_ARG composition in the Eff samples. Additionally, the co-occurrence of MGEs and ARGs in viral genomes was observed, ranging from 22.73 % to 68.75 %. This co-occurrence may exacerbate the persistence and spread of ARGs within WWTPs. The findings present new information on the changes in core ARGs, MGEs, and phage-associated ARGs from influents to effluents in WWTPs and provide new insights into the role of phage-associated ARGs in these systems.


Assuntos
Antibacterianos , Purificação da Água , Antibacterianos/farmacologia , Genes Bacterianos , Águas Residuárias , Metagenoma , Resistência Microbiana a Medicamentos/genética
17.
Int J Biol Macromol ; 261(Pt 2): 129920, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38311128

RESUMO

A novel chestnut porous starch nanoparticle (PSNP) was successfully synthesized, combining the properties of starch nanoparticle (SNP) and porous starch. The SNP obtained through ultrasonic and acid hydrolysis, exhibited a smaller particle size (173.9 nm) and a higher specific surface area (SSA) compared to native starch. After the synergistic hydrolysis by α-amylase and glucoamylase, the porous structure appeared on the surface of SNP. The prepared PSNP had a size of 286.3 nm and the highest SSA. In the adsorption experiments, PSNP showed higher capacities for adsorbing water, oil and methylene blue (MB) compared to other samples. The acid and enzymatic treatments resulted in a decrease in the levels of total starch content and amylose ratio. Furthermore, the treatments increased the levels of relative crystallinity (RC) and solubility, while decreasing the short-range ordered structure and swelling ratio at high temperatures. It was observed that the SSA of starch granules positively correlated with the MB and water adsorption capacity (WAC), solubility, and RC. These findings highlight the potential of the novel PSNP as an efficient adsorbent for bioactive substances and dyes.


Assuntos
Nanopartículas , Amido , Amido/química , Porosidade , Amilose/química , Hidrólise , Água/química
18.
Sci Adv ; 10(8): eadl2238, 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38394209

RESUMO

Skeletal stem cells (SSCs) that are capable of self-renewal and multipotent differentiation contribute to bone development and homeostasis. Several populations of SSCs at different skeletal sites have been reported. Here, we identify a metaphyseal SSC (mpSSC) population whose transcriptional landscape is distinct from other bone mesenchymal stromal cells (BMSCs). These mpSSCs are marked by Sstr2 or Pdgfrb+Kitl-, located just underneath the growth plate, and exclusively derived from hypertrophic chondrocytes (HCs). These HC-derived mpSSCs have properties of self-renewal and multipotency in vitro and in vivo, producing most HC offspring postnatally. HC-specific deletion of Hgs, a component of the endosomal sorting complex required for transport, impairs the HC-to-mpSSC conversion and compromises trabecular bone formation. Thus, mpSSC is the major source of BMSCs and osteoblasts in bone marrow, supporting the postnatal trabecular bone formation.


Assuntos
Osso Esponjoso , Células-Tronco Mesenquimais , Células-Tronco , Osso e Ossos , Diferenciação Celular , Osteoblastos , Osteogênese/genética
19.
Biomed Pharmacother ; 173: 116318, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38401522

RESUMO

Retinal ischemia is a significant factor in various vision-threatening diseases, but effective treatments are currently lacking. This study explores the potential of stem cell factor (SCF) in regulating the neurovascular unit as a therapeutic intervention for retinal ischemic diseases. A chronic retinal ischemia model was established in Brown Norway rats using bilateral common carotid artery occlusion (BCCAO). Subsequent SCF treatment resulted in a remarkable recovery of retinal function, as indicated by electroretinogram, light/dark transition test, and optokinetic head tracking test results. Histological examination demonstrated a significant increase in the number of retinal neurons and an overall thickening of the retina. Immunofluorescence confirmed these findings and further demonstrated that SCF treatment regulated retinal remodeling. Notably, SCF treatment ameliorated the disrupted expression of synaptic markers in the control group's BCCAO rats and suppressed the activation of Müller cells and microglia. Retinal whole-mount analysis revealed a significant improvement in the abnormalities in retinal vasculature following SCF treatment. Transcriptome sequencing analysis revealed that SCF-induced transcriptome changes were closely linked to the Wnt7 pathway. Key members of the Wnt7 pathway, exhibited significant upregulation following SCF treatment. These results underscore the protective role of SCF in the neurovascular unit of retinal ischemia rats by modulating the Wnt7 pathway. SCF administration emerges as a promising therapeutic strategy for retinal ischemia-related diseases, offering potential avenues for future clinical interventions.


Assuntos
Arteriopatias Oclusivas , Doenças das Artérias Carótidas , Doenças Retinianas , Ratos , Animais , Fator de Células-Tronco , Isquemia/metabolismo , Doenças Retinianas/prevenção & controle , Doenças Retinianas/patologia , Retina , Vasos Retinianos/metabolismo , Arteriopatias Oclusivas/patologia
20.
Appl Biochem Biotechnol ; 196(3): 1592-1611, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37436548

RESUMO

Bacterial biofilms (BBFs) exhibit high drug resistance, antiphagocytosis, and extremely strong adhesion, and therefore can cause various diseases. They are also one of the important causes of bacterial infections. Thus, the effective removal of BBFs has attracted considerable research interest. Endolysins, which are efficient antibacterial bioactive macromolecules, have recently been receiving increasing attention. In this study, we overcame the deficiencies of endolysins via immobilization on chitosan nanoparticles (CS-NPs) by preparing LysST-3-CS-NPs using the ionic cross-linking reaction between CS-NPs and LysST-3, an endolysin purified using phage ST-3 expression. The obtained LysST-3-CS-NPs were verified and thoroughly characterized, their antimicrobial activity was investigated using microscopy, and their antibacterial efficacy on polystyrene surfaces was studied. The results obtained suggested that LysST-3-CS-NPs exhibit enhanced bactericidal properties and increased stability and can serve as reliable biocontrol agents for the prevention and treatment of Salmonella biofilm infections.


Assuntos
Quitosana , Nanopartículas , Quitosana/farmacologia , Antibacterianos/farmacologia , Biofilmes , Bactérias
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