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1.
Int J Mol Sci ; 25(16)2024 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-39201769

RESUMEN

African swine fever (ASF) has become a global pandemic due to inadequate prevention and control measures, posing a significant threat to the swine industry. Despite the approval of a single vaccine in Vietnam, no antiviral drugs against the ASF virus (ASFV) are currently available. Aloperine (ALO), a quinolizidine alkaloid extracted from the seeds and leaves of bitter beans, exhibits various biological functions, including anti-inflammatory, anti-cancer, and antiviral activities. In this study, we found that ALO could inhibit ASFV replication in MA-104, PK-15, 3D4/21, and WSL cells in a dose-dependent manner without cytotoxicity at 100 µM. Furthermore, it was verified that ALO acted on the co- and post-infection stages of ASFV by time-of-addition assay, and inhibited viral internalization rather than directly inactivating the virus. Notably, RT-qPCR analysis indicated that ALO did not exert anti-inflammatory activity during ASFV infection. Additionally, gene ontology (GO) and KEGG pathway enrichment analyses of transcriptomic data revealed that ALO could inhibit ASFV replication via the PRLR/JAK2 signaling pathway. Together, these findings suggest that ALO effectively inhibits ASFV replication in vitro and provides a potential new target for developing anti-ASFV drugs.


Asunto(s)
Virus de la Fiebre Porcina Africana , Antivirales , Janus Quinasa 2 , Piperidinas , Quinolizidinas , Transducción de Señal , Replicación Viral , Janus Quinasa 2/metabolismo , Animales , Transducción de Señal/efectos de los fármacos , Replicación Viral/efectos de los fármacos , Quinolizidinas/farmacología , Porcinos , Piperidinas/farmacología , Virus de la Fiebre Porcina Africana/efectos de los fármacos , Virus de la Fiebre Porcina Africana/metabolismo , Antivirales/farmacología , Línea Celular , Fiebre Porcina Africana/virología , Fiebre Porcina Africana/metabolismo
2.
BMC Med Imaging ; 24(1): 220, 2024 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-39160488

RESUMEN

BACKGROUND: Pneumoconiosis has a significant impact on the quality of patient survival. This study aims to evaluate the performance and application value of improved Unet network technology in the recognition and segmentation of lesion areas of lung CT images in patients with pneumoconiosis. METHODS: A total of 1212 lung CT images of patients with pneumoconiosis were retrospectively included. The improved Unet network was used to identify and segment the CT image regions of the patients' lungs, and the image data of the granular regions of the lungs were processed by the watershed and region growing algorithms. After random sorting, 848 data were selected into the training set and 364 data into the validation set. The experimental dataset underwent data augmentation and were used for model training and validation to evaluate segmentation performance. The segmentation results were compared with FCN-8s, Unet network (Base), Unet (Squeeze-and-Excitation, SE + Rectified Linear Unit, ReLU), and Unet + + networks. RESULTS: In the segmentation of lung CT granular region with the improved Unet network, the four evaluation indexes of Dice similarity coefficient, positive prediction value (PPV), sensitivity coefficient (SC) and mean intersection over union (MIoU) reached 0.848, 0.884, 0.895 and 0.885, respectively, increasing by 7.6%, 13.3%, 3.9% and 6.4%, respectively, compared with those of Unet network (Base), and increasing by 187.5%, 249.4%, 131.9% and 51.0%, respectively, compared with those of FCN-8s, and increasing by 14.0%, 31.2%, 4.7% and 9.7%, respectively, compared with those of Unet network (SE + ReLU), while the segmentation performance was also not inferior to that of the Unet + + network. CONCLUSIONS: The improved Unet network proposed shows good performance in the recognition and segmentation of abnormal regions in lung CT images in patients with pneumoconiosis, showing potential application value for assisting clinical decision-making.


Asunto(s)
Neumoconiosis , Tomografía Computarizada por Rayos X , Humanos , Neumoconiosis/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Estudios Retrospectivos , Masculino , Pulmón/diagnóstico por imagen , Interpretación de Imagen Radiográfica Asistida por Computador/métodos , Femenino , Algoritmos , Persona de Mediana Edad , Anciano , Redes Neurales de la Computación
3.
Int J Biol Macromol ; 270(Pt 1): 132209, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38729471

RESUMEN

Recently, the chitosan (CS)-based composites have attracted increasing attention for controlling and preventing the spread of pathogenic microorganisms. Herein, an amphiphilic copolymer containing epoxy and quaternary ammonium groups (PBGDBr) was synthesized via three common acrylate monomers. The epoxy groups of this copolymer were then crosslinked with the amino groups of CS to synthesize a natural/synthetic (PBGDBr-C) composite to increase the water solubility of CS under alkaline conditions and enhance its antibacterial activity based on chemical contact-type modes. Moreover, silver bromide nanoparticles (AgBr NPs)-decorated PBGDBr-C (AgBr@PBGDBr-C) composite was prepared, which aimed to endow the final AgBr@PBGDBr-C composite with a photodynamic antibacterial mode relying on the formation of Ag/AgBr nanostructures catalyzed by visible light on AgBr NPs. The results showed that the final composite possessed satisfactory bactericidal effects at concentrations higher than 64 and 128 µg/mL against Escherichia coli and Staphylococcus aureus, respectively. Additionally, The L929 cells treated with the final composite retained high cell viability (>80 %) at a concentration of 128 µg/mL, indicating its low toxicity to L929 cells. Overall, our synthetic strategy exploits a multi-modal system that enables chemical-photodynamic synergies to treat infections caused by pathogenic bacteria while delaying the development of bacterial resistance.


Asunto(s)
Antibacterianos , Bromuros , Quitosano , Escherichia coli , Compuestos de Plata , Staphylococcus aureus , Quitosano/química , Quitosano/farmacología , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/síntesis química , Bromuros/química , Bromuros/farmacología , Compuestos de Plata/química , Compuestos de Plata/farmacología , Staphylococcus aureus/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Polímeros/química , Polímeros/farmacología , Ratones , Cationes/química , Nanopartículas/química , Nanopartículas del Metal/química , Animales , Supervivencia Celular/efectos de los fármacos , Línea Celular
4.
Exp Parasitol ; 262: 108788, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38759775

RESUMEN

Giardiasis is a common waterborne zoonotic disease caused by Giardia intestinalis. Upon infection, Giardia releases excretory and secretory products (ESPs) including secreted proteins (SPs) and extracellular vesicles (EVs). Although the interplay between ESPs and intestinal epithelial cells (IECs) has been previously described, the functions of EVs in these interactions and their differences from those of SPs require further exploration. In the present study, EVs and EV-depleted SPs were isolated from Giardia ESPs. Proteomic analyses of isolated SPs and EVs showed 146 and 91 proteins, respectively. Certain unique and enriched proteins have been identified in SPs and EVs. Transcriptome analysis of Caco-2 cells exposed to EVs showed 96 differentially expressed genes (DEGs), with 56 upregulated and 40 downregulated genes. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) indicated that Caco-2 genes related to metabolic processes, the HIF-1 signaling pathway, and the cAMP signaling pathway were affected. This study provides new insights into host-parasite interactions, highlighting the potential significance of EVs on IECs during infections.


Asunto(s)
Vesículas Extracelulares , Giardia lamblia , Mucosa Intestinal , Humanos , Células CACO-2 , Giardia lamblia/genética , Giardia lamblia/metabolismo , Vesículas Extracelulares/metabolismo , Mucosa Intestinal/parasitología , Mucosa Intestinal/metabolismo , Perfilación de la Expresión Génica , Células Epiteliales/parasitología , Células Epiteliales/metabolismo , Proteómica , Interacciones Huésped-Parásitos , Expresión Génica , Transcriptoma , Giardiasis/parasitología
5.
Virol Sin ; 39(3): 469-477, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38789040

RESUMEN

Virus replication relies on complex interactions between viral proteins. In the case of African swine fever virus (ASFV), only a few such interactions have been identified so far. In this study, we demonstrate that ASFV protein p72 interacts with p11.5 using co-immunoprecipitation and liquid chromatography-mass spectrometry (LC-MS). It was found that protein p72 interacts specifically with p11.5 â€‹at sites amino acids (aa) 1-216 of p72 and aa 1-68 of p11.5. To assess the importance of p11.5 in ASFV infection, we developed a recombinant virus (ASFVGZΔA137R) by deleting the A137R gene from the ASFVGZ genome. Compared with ASFVGZ, the infectious progeny virus titers of ASFVGZΔA137R were reduced by approximately 1.0 logs. In addition, we demonstrated that the growth defect was partially attributable to a higher genome copies-to-infectious virus titer ratios produced in ASFVGZΔA137R-infected MA104 â€‹cells than in those infected with ASFVGZ. This finding suggests that MA104 â€‹cells infected with ASFVGZΔA137R may generate larger quantities of noninfectious particles. Importantly, we found that p11.5 did not affect virus-cell binding or endocytosis. Collectively, we show for the first time the interaction between ASFV p72 and p11.5. Our results effectively provide the relevant information of the p11.5 protein. These results extend our understanding of complex interactions between viral proteins, paving the way for further studies of the potential mechanisms and pathogenesis of ASFV infection.


Asunto(s)
Virus de la Fiebre Porcina Africana , Proteínas Virales , Replicación Viral , Virus de la Fiebre Porcina Africana/genética , Virus de la Fiebre Porcina Africana/fisiología , Animales , Porcinos , Proteínas Virales/metabolismo , Proteínas Virales/genética , Chlorocebus aethiops , Fiebre Porcina Africana/virología , Fiebre Porcina Africana/metabolismo , Línea Celular , Unión Proteica , Cromatografía Liquida , Células Vero , Espectrometría de Masas
6.
Cell Death Discov ; 10(1): 82, 2024 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-38365768

RESUMEN

There are multiple published data showing that excessive oxidative stress contributes to bone loss and even bone tissue damage, and it is also correlated with the pathophysiology of bone degenerative diseases, including osteoporosis (OP). Garcinol, a polyisoprenylated benzophenone derivative, has been recently established as an anti-oxidant agent. However, it remains elusive whether Garcinol protects bone marrow mesenchymal stem cells (BMSCs) and bone tissue from oxidative stress-induced damage. Here, we explored the potential effects of Garcinol supplementation in ameliorating oxidative stimulation-induced dysfunction of BMSCs and bone loss in osteoporotic mice. In this study, we verified that Garcinol exerted potent protective functions in the hydrogen peroxide (H2O2)-induced excessive oxidative stress and dysfunction of BMSCs. Besides, Garcinol was also identified to improve the reduced bone mass and abnormal lineage commitment of BMSCs in the condition of OP by suppressing the oxidative stimulation. Subsequent analysis revealed that nuclear factor erythroid 2-related factor 2 (NRF2) might be a key regulator in the sheltering effects of Garcinol on the H2O2-regulated oxidative stress, and the protective functions of Garcinol was mediated by NRF2-antioxidant signaling. Collectively, Garcinol prevented oxidative stress-related BMSC damage and bone loss through the NRF2-antioxidant signaling, which suggested the promising therapeutic values of Garcinol in the treatment of oxidative stress-related bone loss. Therefore, Garcinol might contribute to treating OP.

7.
PLoS One ; 19(2): e0297783, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38386625

RESUMEN

OBJECTIVE: Pain is a frequent adverse reaction during orthodontic treatment, which can significantly reduce treatment compliance and compromise the expected treatment effect. Physical interventions have been used to alleviate pain after orthodontic treatment, but their effectiveness is controversial. This study used a network meta-analysis to assess the efficacy of various physical interventions typically used in managing pain after orthodontic treatment, with a view to provide evidence-based recommendations for representative interventions for orthodontic pain relief during peak pain intensity. METHODS: A systematic search of six electronic databases, from their respective inception dates, was conducted to identify relevant literature on the efficacy of various typical physical interventions for managing pain after orthodontic treatment. Literature screening was performed according to the Cochrane System Evaluator's Manual. Stata 16.0 was used to assess heterogeneity, inconsistency, publication bias, and sensitivity to generate an evidence network diagram and conduct a network meta-analysis. RESULTS: In total, 771 articles were reviewed to collect literature on interventions, including low-level laser therapy (LLLT), vibration, acupuncture, and chewing. Of these, 28 studies using a visual analog scale (VAS) as an outcome indicator were included. The results showed that LLLT, vibration, acupuncture, and chewing effectively relieved the pain symptoms in patients after orthodontic treatment. At 24 h post-treatment, LLLT (surface under the cumulative ranking curve [SUCRA] = 80.8) and vibration (SUCRA = 71.1) were the most effective interventions. After 48 h of treatment, acupuncture (SUCRA = 89.6) showed a definite advantage as the best intervention. CONCLUSION: LLLT, vibration, acupuncture, and chewing can alleviate pain associated with orthodontic treatment. Among these interventions, acupuncture was found to be the most effective at 48 h after orthodontic treatment. In addition, acupuncture demonstrated long-lasting and stable pain-relieving effects. However, further studies are needed to determine the most suitable equipment-specific parameters for acupuncture in relieving pain associated with orthodontic treatment.


Asunto(s)
Manejo del Dolor , Humanos , Manejo del Dolor/métodos , Terapia por Luz de Baja Intensidad/métodos , Metaanálisis en Red , Ortodoncia/métodos , Ortodoncia Correctiva/efectos adversos , Dimensión del Dolor , Vibración/uso terapéutico , Terapia por Acupuntura/métodos , Dolor/prevención & control , Dolor/etiología
8.
J Virol ; 98(3): e0194423, 2024 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-38421166

RESUMEN

Since the first human infection reported in 2013, H7N9 avian influenza virus (AIV) has been regarded as a serious threat to human health. In this study, we sought to identify the virulence determinant of the H7N9 virus in mammalian hosts. By comparing the virulence of the SH/4664 H7N9 virus, a non-virulent H9N2 virus, and various H7N9-H9N2 hybrid viruses in infected mice, we first pinpointed PB2 as the primary viral factor accounting for the difference between H7N9 and H9N2 in mammalian virulence. We further analyzed the in vivo effects of individually mutating H7N9 PB2 residues different from the closely related H9N2 virus and consequently found residue 473, alongside the well-known residue 627, to be critical for the virulence of the H7N9 virus in mice and the activity of its reconstituted viral polymerase in mammalian cells. The importance of PB2-473 was further strengthened by studying reverse H7N9 substitutions in the H9N2 background. Finally, we surprisingly found that species-specific usage of ANP32A, a family member of host factors connecting with the PB2-627 polymorphism, mediates the contribution of PB2 473 residue to the mammalian adaption of AIV polymerase, as the attenuating effect of PB2 M473T on the viral polymerase activity and viral growth of the H7N9 virus could be efficiently complemented by co-expression of chicken ANP32A but not mouse ANP32A and ANP32B. Together, our studies uncovered the PB2 473 residue as a novel viral host range determinant of AIVs via species-specific co-opting of the ANP32 host factor to support viral polymerase activity.IMPORTANCEThe H7N9 avian influenza virus has been considered to have the potential to cause the next pandemic since the first case of human infection reported in 2013. In this study, we identified PB2 residue 473 as a new determinant of mouse virulence and mammalian adaptation of the viral polymerase of the H7N9 virus and its non-pathogenic H9N2 counterparts. We further demonstrated that the variation in PB2-473 is functionally linked to differential co-opting of the host ANP32A protein in supporting viral polymerase activity, which is analogous to the well-known PB2-627 polymorphism, albeit the two PB2 positions are spatially distant. By providing new mechanistic insight into the PB2-mediated host range determination of influenza A viruses, our study implicated the potential existence of multiple PB2-ANP32 interfaces that could be targets for developing new antivirals against the H7N9 virus as well as other mammalian-adapted influenza viruses.


Asunto(s)
Subtipo H7N9 del Virus de la Influenza A , Gripe Humana , Proteínas Nucleares , Proteínas de Unión al ARN , Animales , Humanos , Ratones , Subtipo H7N9 del Virus de la Influenza A/metabolismo , Subtipo H7N9 del Virus de la Influenza A/patogenicidad , Subtipo H9N2 del Virus de la Influenza A , Gripe Humana/virología , Mamíferos , Proteínas Nucleares/metabolismo , Nucleotidiltransferasas/metabolismo , Proteínas de Unión al ARN/metabolismo , ARN Polimerasa Dependiente del ARN/genética , ARN Polimerasa Dependiente del ARN/metabolismo , Virulencia , Replicación Viral
9.
Viruses ; 16(2)2024 02 18.
Artículo en Inglés | MEDLINE | ID: mdl-38400086

RESUMEN

The CRISPR/Cas9 system is widely used to manipulate viral genomes. Although Alphaherpesvirinae genomes are large and complicated to edit, in recent years several Pseudorabies virus (PRV) mutants have been successfully generated using the CRISPR/Cas9 system. However, the application of CRISPR/Cas9 editing on another member of alpha herpesviruses, bovine herpesvirus-1 (BHV-1), is rarely reported. This paper reports a rapid and straightforward approach to manipulating herpesviruses genome using CRISPR/Cas9. The recombinant plasmids contained the left and right arm of the thymidine kinase (TK) gene of PRV or of the glycoprotein I (gI) and glycoprotein E (gE) of BHV-1. Upon the cleavage of the TK or gIgE gene by Cas9 protein, this was replaced by the enhanced green fluorescence protein (eGFP) by homologous recombination. With this approach, we generated recombinant TK-/eGFP+ PRV and gIgE-/eGFP+ BHV-1 mutants and then proceeded to characterize their biological activities in vitro and in vivo. In conclusion, we showed that alpha herpesvirus, including PRV and BHV-1, can be rapidly edited using the CRISPR/Cas9 approach paving the way to the development of animal herpesvirus vaccines.


Asunto(s)
Herpesvirus Bovino 1 , Herpesvirus Suido 1 , Seudorrabia , Animales , Edición Génica , Sistemas CRISPR-Cas , Herpesvirus Bovino 1/genética , Herpesvirus Bovino 1/metabolismo , Seudorrabia/prevención & control , Glicoproteínas/genética
10.
Elife ; 122024 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-38289829

RESUMEN

Despite the recognized importance of the spinal cord in sensory processing, motor behaviors, and neural diseases, the underlying organization of neuronal clusters and their spatial location remain elusive. Recently, several studies have attempted to define the neuronal types and functional heterogeneity in the spinal cord using single-cell or single-nucleus RNA sequencing in animal models or developing humans. However, molecular evidence of cellular heterogeneity in the adult human spinal cord is limited. Here, we classified spinal cord neurons into 21 subclusters and determined their distribution from nine human donors using single-nucleus RNA sequencing and spatial transcriptomics. Moreover, we compared the human findings with previously published single-nucleus data of the adult mouse spinal cord, which revealed an overall similarity in the neuronal composition of the spinal cord between the two species while simultaneously highlighting some degree of heterogeneity. Additionally, we examined the sex differences in the spinal neuronal subclusters. Several genes, such as SCN10A and HCN1, showed sex differences in motor neurons. Finally, we classified human dorsal root ganglia (DRG) neurons using spatial transcriptomics and explored the putative interactions between DRG and spinal cord neuronal subclusters. In summary, these results illustrate the complexity and diversity of spinal neurons in humans and provide an important resource for future research to explore the molecular mechanisms underlying spinal cord physiology and diseases.


Asunto(s)
Médula Espinal , Transcriptoma , Ratones , Animales , Adulto , Humanos , Femenino , Masculino , Neuronas Motoras , Perfilación de la Expresión Génica , Ganglios Espinales , Análisis de Secuencia de ARN
11.
Vet Microbiol ; 290: 110002, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38295489

RESUMEN

African swine fever has caused substantial economic losses to China`s pig industry in recent years. Currently, the highly pathogenic African swine fever virus strain of genotype II is predominantly circulating in China, accompanied by a series of emerging isolates displaying unique genetic variations. The pathogenicity of these emerging strains is still unclear. Recently, a novel ASFV strain with a distinguishable three-large-fragment gene deletion was obtained from the field specimens, and its in vivo pathogenicity and transmission were evaluated in this study. The animal experiment involved inoculating a high dose of YNFN202103 and comparing its effects with those of the highly pathogenic strain GZ201801_2. Results showed that pigs infected by YNFN202103 exhibited significantly prolonged onset and survival time, lower viremia levels, and less severe histopathological lesions compared to GZ201801_2. These findings contributed valuable insights into the pathogenicity and transmission of ASFV and its prevention and eradication strategies in practical settings.


Asunto(s)
Virus de la Fiebre Porcina Africana , Fiebre Porcina Africana , Enfermedades de los Porcinos , Porcinos , Animales , Virus de la Fiebre Porcina Africana/genética , Virulencia/genética , Eliminación de Gen , China , Enfermedades de los Porcinos/genética
12.
Int J Biol Sci ; 20(2): 569-584, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38169625

RESUMEN

Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease (ESRD). Mitochondrial dysfunction in renal tubules, occurring early in the disease, is linked to the development of DKD, although the underlying pathways remain unclear. Here, we examine diabetic human and mouse kidneys, and HK-2 cells exposed to high glucose, to show that high glucose disrupts mitochondria-associated endoplasmic reticulum membrane (MAM) and causes mitochondrial fragmentation. We find that high glucose conditions increase mitogen-activated protein kinase 1(MAPK1), a member of the MAP kinase signal transduction pathway, which in turn lowers the level of phosphofurin acidic cluster sorting protein 2 (PACS-2), a key component of MAM that tethers mitochondria to the ER. MAPK1-induced disruption of MAM leads to mitochondrial fragmentation but this can be rescued in HK-2 cells by increasing PACS-2 levels. Functional studies in diabetic mice show that inhibition of MAPK1 increases PACS-2 and protects against the loss of MAM and the mitochondrial fragmentation. Taken together, these results identify the MAPK1-PACS-2 axis as a key pathway to therapeutically target as well as provide new insights into the pathogenesis of DKD.


Asunto(s)
Diabetes Mellitus Experimental , Nefropatías Diabéticas , Enfermedades Mitocondriales , Ratones , Humanos , Animales , Diabetes Mellitus Experimental/complicaciones , Proteína Quinasa 1 Activada por Mitógenos , Glucosa
13.
J Control Release ; 365: 716-728, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38036004

RESUMEN

Antiviral vaccine is essential for preventing and controlling virus spreading, along with declining morbidity and mortality. A major challenge in effective vaccination lies in the ability to enhance both the humoral and cellular immune responses by adjuvants. Herein, self-assembled nanoparticles based on graphene oxide quantum dots with components of carnosine, resiquimod and Zn2+ ions, namely ZnGC-R, are designed as a new adjuvant for influenza vaccine. With its high capability for antigen-loading, ZnGC-R enhances antigen utilization, improves DC recruitment, and activates antigen-presenting cells. Single cell analysis of lymphocytes after intramuscular vaccination revealed that ZnGC-R generated multifaceted immune responses. ZnGC-R stimulated robust CD4+CCR7loPD-1hi Tfh and durable CD8+CD44hiCD62L- TEM immune responses, and simultaneously promoted the proliferation of CD26+ germinal center B cells. Besides, ZnGC-R elicited 2.53-fold higher hemagglutination-inhibiting antibody than commercial-licensed aluminum salt adjuvant. ZnGC-R based vaccine induced 342% stronger IgG antibody responses compared with vaccines with inactivated virus alone, leading to 100% in vivo protection efficacy against the H1N1 influenza virus challenge.


Asunto(s)
Grafito , Subtipo H1N1 del Virus de la Influenza A , Vacunas contra la Influenza , Infecciones por Orthomyxoviridae , Humanos , Adyuvantes Inmunológicos/farmacología , Inmunidad Celular , Adyuvantes Farmacéuticos/farmacología , Anticuerpos Antivirales , Infecciones por Orthomyxoviridae/prevención & control
14.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1006519

RESUMEN

Objective@#To explore the molecular mechanism of resveratrol (RES) in the treatment of oral squamous cell carcinoma (OSCC) through the use of biological information methods such as network pharmacology and molecular docking and to provide a theoretical reference for the clinical application of RES in the treatment of OSCC.@*Methods@#The Swiss Target Prediction(http://www.swisstargetprediction.ch), SEA (http://sea.bkslab.org)database, and Pharm mapper database(http://lilab-ecust.cn) were used to retrieve RES-related targets, and the DISGENET (www.disgenet.org), OMIM (https://omim.org) and GeneCards (https://www.genecards.org) databases were used to screen OSCC disease targets. The intersection of drugs and disease targets was determined, and Cytoscape 3.7.2 software was used to construct a "drug-diseasetarget pathway" network. The Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database was used to construct a target protein interaction network, and the DAVID database was used for enrichment analysis of key proteins. Finally, molecular docking validation of key proteins was performed using AutoDock and PyMOL. The enrichment analysis and molecular docking results were integrated to predict the possible molecular mechanisms of RES treatment in OSCC; western blot was used to determine the effect of resveratrol at different concentrations (50, 100) μmol/L on the expression of Src tyrosine kinase (SRC), epidermal growth factor receptor (EGFR), estrogen receptor gene 1 (ESR1), and phosphatidylinositol 3 kinase/protein kinase B (PI3K/AKT) signaling pathway proteins in OSCC HSC-3 cells.@*Results@#A total of 243 targets of RES drugs and 6 094 targets of OSCC were identified. A total of 116 potential common targets were obtained by intersecting drugs with disease targets. These potential targets mainly participate in biological processes such as in vivo protein self-phosphorylation, peptide tyrosine phosphorylation, transmembrane receptor protein tyrosine kinase signaling pathway, and positive regulation of RNA polymerase Ⅱ promoter transcription, and they interfere with the PI3K/AKT signaling pathway to exert anti-OSCC effects. The docking results of resveratrol with OSCC molecules indicated that key targets, such as EGFR, ESR1, and SRC, have good binding activity. The results of cell-based experiments showed that resveratrol inhibited the protein expression of SRC, EGFR, ESR1, p-PI3K, and p-AKT in HSC-3 cells in a dose-dependent manner.@*Conclusion@#RES can inhibit the expression of its targets EGFR, ESR1, SRC, p-PI3K, and p-AKT in OSCC cells.

15.
Medicine (Baltimore) ; 102(48): e36424, 2023 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-38050256

RESUMEN

BACKGROUND: Femoral neck fractures in young adults(<65 years), have always been a difficult problem, characterized by high rates of nonunion and avascular necrosis (AVN). The clinical efficacy of anatomical reduction and non-anatomical reduction methods needs to be supported by clinical data. Therefore, we conduct a meta-analysis on the clinical efficacy of different reduction methods to better guide clinical practice. METHODS: Relevant studies published using internal fixation to treat femoral neck fracture in several databases were searched. The outcomes sought included Harris score and the rate of AVN, nonunion and femoral neck shortening (<5 mm). Included studies were assessed for methodological bias and estimates of effect were calculated. Potential reasons for heterogeneity were explored. RESULTS: The clinical results showed that compared with the anatomical reduction and positive buttress, there is no significant difference in the rate of AVN (OR = 0.87, 95%CI: 0.55-1.37, P = .55), nonunion (OR = 0.54, 95%CI: 0.21-1.41, P = .21), femoral neck shortening (<5 mm) (OR = 1.03,95%CI: 0.57-1.86, P = .92), the Harris score (MD = -0.28, 95%CI: -1.36-0.80, P = .61) and the excellent and good rate of Harris score (OR = 1.73, 95%CI: 0.84-3.56, P = .61). However, compared with negative buttress, the rate of AVN (OR = 0.62, 95%CI: 0.38-1.01, P = .05), nonunion (OR = 0.34, 95%CI: 0.12-1.00, P = .05) and femoral neck shortening (<5 mm) (OR = 0.27, 95%CI: 0.16-0.45, P < .00001) were significantly lower, and the Harris score (MD = 6.53, 95%CI: 2.55 ~ 10.51, P = .001) was significantly better in positive buttress. CONCLUSIONS: In the case of difficult to achieve anatomical reduction, for young patients (< 65 years) with femoral neck fracture, reduction with positive buttress can be an excellent alternative and negative buttress should be avoided as much as possible.


Asunto(s)
Fracturas del Cuello Femoral , Osteonecrosis , Adulto Joven , Humanos , Fijación Interna de Fracturas/métodos , Resultado del Tratamiento , Fracturas del Cuello Femoral/cirugía , Factores de Riesgo , Estudios Retrospectivos
16.
Am J Cancer Res ; 13(8): 3531-3546, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37693132

RESUMEN

Longitudinal studies have indicated the pivotal role of natural killer cells (NKs) in the elimination of certain infections and malignancies. Currently, perinatal blood (PB) and cord blood (CB) have been considered with promising prospective for autogenous and allogeneic NKs transplantation, yet the similarities and differences at the biological and molecular levels are largely obscure. We isolated mononuclear cells (MNCs) from PB and CB, and compared the biological phenotypes of resident NKs by flow cytometry and cell counting. Then, we turned to our well-established "3ILs" strategy and co-culture for NK cell activation and cytotoxicity analyses, respectively. Finally, with the aid of transcriptomic analyses, we further dissected the signatures of PB-NKs and CB-NKs. CB-NKs revealed superiority in cellular vitality over PB-NKs, together with variations in subpopulations. CB-NKs showed higher cytotoxicity over PB-NKs against K562 cells. Furthermore, we found both NKs revealed multifaceted conservations and differences in gene expression profiling and genetic variations, together with gene subsets and signaling pathway. Collectively, both NKs revealed multifaceted similarities and diverse variations at the cellular and transcriptomic levels. Our findings would benefit the further exploration of the biological and transcriptomic properties of CB-NKs and PB-NKs, together with the development of NK cell-based cytotherapy.

17.
Plant Physiol Biochem ; 203: 108038, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37722283

RESUMEN

Virus-infected Panax notoginseng plants with chlorotic, mosaic, and pitted leaves are ubiquitous in the primary P. notoginseng-producing region in Wenshan autonomous prefecture, Yunnan province, China. However, the viruses that infect P. notoginseng and the effects of viral infections on the biosynthesis of secondary metabolites and photosynthesis remain unknown. This study identified a variety of viruses infecting P. notoginseng plants via deep-sequencing of small RNA (sRNA). Of the 10 identified viruses, seven had not previously been detected in P. notoginseng, including Cauliflower mosaic virus and Soybean chlorotic mottle virus. In addition, the simultaneous infection of P. notoginseng by Panax notoginseng virus A (PnVA), Panax cryptic virus 4 (PCV4), and Tomato yellow leaf curl China virus (TYLCCNV) was confirmed by PCR. Moreover, a quantitative PCR analysis showed that the expression levels of key genes related to saponin biosynthesis were generally down-regulated in the virus-infected P. notoginseng. Additionally, high-performance liquid chromatography results indicated the saponin content decreased in the roots of virus-infected P. notoginseng plants. The activities of photosynthesis-related enzymes, including ribulose-1,5-bisphosphate carboxylase/oxygenase, fructose 1,6-bisphosphatase, and fructose 1,6-biphosphate aldolase, decreased significantly in the virus-infected P. notoginseng plants. The viral infections also induced the expression of antioxidant genes and increased antioxidant enzyme activities. Furthermore, the expression levels of many resistance-related genes were up-regulated in P. notoginseng plants inoculated with a viral suspension. The study results provide the foundation for future research on P. notoginseng viral diseases, which may lead to the development of enhanced disease control measures.

18.
ACS Appl Mater Interfaces ; 15(38): 44912-44920, 2023 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-37712229

RESUMEN

Solar energy conversion devices with charge-selective contacts are attracting significant research interest as a cost-effective alternative to homojunction counterparts. This study presents a novel approach for fabricating high-performance solar cells based on InP heterojunctions using a solution-processed ferri-hydrite (Fh) electron-selective contact (ESC). The champion cell efficiency of 16.6% is achieved, which is a significant improvement over those from previous studies using other solution-processed ESC materials. X-ray photoelectron spectroscopy measurements showed that the low conduction band offset at the Fh-InP interface facilitated selective transport of photogenerated electrons from InP. Moreover, the Fh electron-selective contact layer provided an excellent photoelectrochemical half-cell water reduction efficiency of 8.4%. The Fh layer not only selectively extracts photogenerated electrons from InP but also simultaneously serves as a surface protection layer, improving the cell's long-term stability. These results demonstrate the potential of Fh as a low-cost and easily fabricated material for use in high-efficiency photovoltaic and photoelectrochemical devices. Our findings pave the way for further improvements in the efficiency of InP heterojunction solar cells by addressing the losses incurred in the cells.

19.
Animals (Basel) ; 13(13)2023 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-37444008

RESUMEN

To explore the differences in the growth characteristics and population dynamics of Schizothorax wangchiachii populations in the Jinsha River (JSR) and the Yalong River (YLR), samples were collected in the upper reaches of the JSR (n = 230) from 2019 to 2020 and the middle reaches of the YLR (n = 187) from 2017 to 2018. In the JSR and YLR populations, the age range was 11 and 12 years old, respectively, and the best growth equation was the Von Bertalanffy equation. The comparative analysis of the two populations showed that the growth coefficient, initial sexual maturity age and age at first capture of the YLR population were greater than those of the JSR population. Comparing the mortality rates of the two groups, we found that the YLR population had the higher female mortality rate (0.658 years-1) and the lower male mortality rate (0.453 years-1). Our assessment of the three natural mortality rates showed that the Fcur of both male and female populations was greater than F25%, indicating that both populations were in an overexploited state. Therefore, we suggest considering the two groups as separate protection units and implementing management measures such as ecological regulation, restoration of tributary habitat and strengthening of fishing ban monitoring to protect their resources.

20.
Heliyon ; 9(6): e17224, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37360096

RESUMEN

Background: Clear cell renal cell carcinoma (ccRCC) is a common urinary cancer. Although diagnostic and therapeutic approaches for ccRCC have been improved, the survival outcomes of patients with advanced ccRCC remain unsatisfactory. Fatty acid metabolism (FAM) has been increasingly recognized as a critical modulator of cancer development. However, the significance of the FAM in ccRCC remains unclear. Herein, we explored the function of a FAM-related risk score in the stratification and prediction of treatment responses in patients with ccRCC. Methods: First, we applied an unsupervised clustering method to categorize patients from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) datasets into subtypes and retrieved FAM-related genes from the MSigDB database. We discern differentially expressed genes (DEGs) among different subtypes. Then, we applied univariate Cox regression analysis followed by least absolute shrinkage and selection operator (LASSO) linear regression based on DEGs expression to establish a FAM-related risk score for ccRCC. Results: We stratified the three ccRCC subtypes based on FAM-related genes with distinct overall survival (OS), clinical features, immune infiltration patterns, and treatment sensitivities. We screened nine genes from the FAM-related DEGs in the three subtypes to establish a risk prediction model for ccRCC. Nine FAM-related genes were differentially expressed in the ccRCC cell line ACHN compared to the normal kidney cell line HK2. High-risk patients had worse OS, higher genomic heterogeneity, a more complex tumor microenvironment (TME), and elevated expression of immune checkpoints. This phenomenon was validated in the ICGC cohort. Conclusion: We constructed a FAM-related risk score that predicts the prognosis and therapeutic response of ccRCC. The close association between FAM and ccRCC progression lays a foundation for further exploring FAM-related functions in ccRCC.

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