Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 372
Filtrar
1.
Front Immunol ; 15: 1374368, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38715616

RESUMO

NOD1 and NOD2 as two representative members of nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family play important roles in antimicrobial immunity. However, transcription mechanism of nod1 and nod2 and their signal circle are less understood in teleost fish. In this study, with the cloning of card9 and ripk2 in Chinese perch, the interaction between NOD1, NOD2, and CARD9 and RIPK2 were revealed through coimmunoprecipitation and immunofluorescence assays. The overexpression of NOD1, NOD2, RIPK2 and CARD9 induced significantly the promoter activity of NF-κB, IFNh and IFNc. Furthermore, it was found that nod1 and nod2 were induced by poly(I:C), type I IFNs, RLR and even NOD1/NOD2 themselves through the ISRE site of their proximal promoters. It is thus indicated that nod1 and nod2 can be classified also as ISGs due to the presence of ISRE in their proximal promoter, and their expression can be mechanistically controlled through PRR pathway as well as through IFN signaling in antiviral immune response.


Assuntos
Proteínas de Peixes , Proteína Adaptadora de Sinalização NOD1 , Proteína Adaptadora de Sinalização NOD2 , Proteína Serina-Treonina Quinase 2 de Interação com Receptor , Transdução de Sinais , Animais , Proteína Adaptadora de Sinalização NOD1/genética , Proteína Adaptadora de Sinalização NOD1/metabolismo , Proteína Serina-Treonina Quinase 2 de Interação com Receptor/metabolismo , Proteína Serina-Treonina Quinase 2 de Interação com Receptor/genética , Proteína Adaptadora de Sinalização NOD2/genética , Proteína Adaptadora de Sinalização NOD2/metabolismo , Proteínas de Peixes/genética , Proteínas de Peixes/metabolismo , Proteínas de Peixes/imunologia , Percas/genética , Percas/imunologia , Percas/metabolismo , Interferons/metabolismo , Interferons/genética , Regiões Promotoras Genéticas , Transcrição Gênica , Imunidade Inata/genética , Ligação Proteica
2.
Eur J Med Chem ; 273: 116500, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38776807

RESUMO

The deficiency in available targeted agents and frequency of chemoresistance are primary challenges in clinical management of triple-negative breast cancer (TNBC). The aberrant expression of USP21 and JAK2 represents a characterized mechanism of TNBC progression and resistance to paclitaxel (PTX). Despite its clear that high expression of USP21-mediated de-ubiquitination leads to increased levels of JAK2 protein, we lack regulator molecules to dissect the mechanisms that the interaction between USP21 and JAK2 contributes to the phenotype and resistance of TNBC. Here, we report a USP21/JAK2/STAT3 axis-targeting regulator 13c featuring a N-anthraniloyl tryptamine scaffold that showed excellent anti-TNBC potency and promising safety profile. Importantly, the therapeutic potential of using 13c in combination with PTX in PTX-resistant TNBC was demonstrated. This study showcases N-anthraniloyl tryptamine derivatives as a novel anti-TNBC chemotype with a pharmacological mode of action targeting the USP21/JAK2/STAT3 axis and provides a potential therapeutic target for the treatment of TNBC.

3.
Food Chem ; 453: 139581, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38754354

RESUMO

This study investigated the impact of ultrasound treatment on dioscorin, the primary storage protein found in yam tubers. Three key factors, namely ultrasound power, duration, and frequency, were focused on. The research revealed that ultrasound-induced cavitation effects disrupted non-covalent bonds, resulting in a reduction in α-helix and ß-sheet contents, decreased thermal stability, and a decrease in the apparent hydrodynamic diameter (Dh) of dioscorin. Additionally, previously hidden amino acid groups within the molecule became exposed on its surface, resulting in increased surface hydrophobicity (Ho) and zeta-potential. Under specific ultrasound conditions (200 W, 25 kHz, 30 min), Dh decreased while Ho increased, facilitating the adsorption of dioscorin molecules onto the oil-water interface. Molecular dynamics (MD) simulations showed that at lower frequencies and pressures, the structural flexibility of dioscorin's main chain atoms increased, leading to more significant fluctuations between amino acid residues. This transformation improved dioscorin's emulsifying properties and its oil-water interface affinity.

4.
Cell Rep Med ; 5(5): 101554, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38729157

RESUMO

The axons of retinal ganglion cells (RGCs) form the optic nerve, transmitting visual information from the eye to the brain. Damage or loss of RGCs and their axons is the leading cause of visual functional defects in traumatic injury and degenerative diseases such as glaucoma. However, there are no effective clinical treatments for nerve damage in these neurodegenerative diseases. Here, we report that LIM homeodomain transcription factor Lhx2 promotes RGC survival and axon regeneration in multiple animal models mimicking glaucoma disease. Furthermore, following N-methyl-D-aspartate (NMDA)-induced excitotoxicity damage of RGCs, Lhx2 mitigates the loss of visual signal transduction. Mechanistic analysis revealed that overexpression of Lhx2 supports axon regeneration by systematically regulating the transcription of regeneration-related genes and inhibiting transcription of Semaphorin 3C (Sema3C). Collectively, our studies identify a critical role of Lhx2 in promoting RGC survival and axon regeneration, providing a promising neural repair strategy for glaucomatous neurodegeneration.


Assuntos
Axônios , Modelos Animais de Doenças , Glaucoma , Proteínas com Homeodomínio LIM , Regeneração Nervosa , Células Ganglionares da Retina , Fatores de Transcrição , Animais , Células Ganglionares da Retina/metabolismo , Células Ganglionares da Retina/patologia , Proteínas com Homeodomínio LIM/metabolismo , Proteínas com Homeodomínio LIM/genética , Glaucoma/genética , Glaucoma/patologia , Glaucoma/metabolismo , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Axônios/metabolismo , Axônios/patologia , Camundongos , Regeneração Nervosa/genética , Regeneração Nervosa/fisiologia , Camundongos Endogâmicos C57BL , Sobrevivência Celular/genética , Semaforinas/metabolismo , Semaforinas/genética , N-Metilaspartato/metabolismo
5.
J Fungi (Basel) ; 10(5)2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38786704

RESUMO

Autophagy, a conserved cellular recycling process, plays a crucial role in maintaining homeostasis under stress conditions. It also regulates the development and virulence of numerous filamentous fungi. In this study, we investigated the specific function of ATG8, a reliable autophagic marker, in the opportunistic pathogen Aspergillus flavus. To investigate the role of atg8 in A. flavus, the deletion and complemented mutants of atg8 were generated according to the homologous recombination principle. Deletion of atg8 showed a significant decrease in conidiation, spore germination, and sclerotia formation compared to the WT and atg8C strains. Additionally, aflatoxin production was found severely impaired in the ∆atg8 mutant. The stress assays demonstrated that ATG8 was important for A. flavus response to oxidative stress. The fluorescence microscopy showed increased levels of reactive oxygen species in the ∆atg8 mutant cells, and the transcriptional result also indicated that genes related to the antioxidant system were significantly reduced in the ∆atg8 mutant. We further found that ATG8 participated in regulating the pathogenicity of A. flavus on crop seeds. These results revealed the biological role of ATG8 in A. flavus, which might provide a potential target for the control of A. flavus and AFB1 biosynthesis.

6.
Sleep Med ; 119: 155-163, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38678759

RESUMO

OBJECTIVES: Sleep is associated with cognitive function in older adults. In the current study, we examined this relationship from subjective and objective perspectives, and determined the robustness and dimensional specificity of the associations using a comprehensive modelling approach. METHODS: Multiple dimensions of subjective (sleep quality and daytime sleepiness) and objective sleep (sleep stages, sleep parameters, sleep spindles, and slow oscillations), as well as subjectively reported and objectively measured cognitive function were collected from 55 older adults. Specification curve analysis was used to examine the robustness of correlations for the effects of sleep on cognitive function. RESULTS: Robust associations were found between sleep and objectively measured cognitive function, but not with subjective cognitive complaints. In addition, subjective sleep showed robust and consistent associations with global cognitive function, whereas objective sleep showed a more domain-specific association with episodic memory. Specifically, subjective sleep quality and daytime sleepiness correlated with global cognitive function, and objective sleep parameters correlated with episodic memory. CONCLUSIONS: Overall, associations between sleep and cognitive function in older adults depend on how they are measured and which specific dimensions of sleep and domains of cognitive function are considered. It highlights the importance of focusing on specific associations to ameliorate the detrimental effects of sleep disturbance on cognitive function in later life.

7.
Chem Commun (Camb) ; 60(25): 3413-3416, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38441256

RESUMO

A photoredox-catalyzed unsymmetrical diamination of alkenes by using N-aminopyridinium salts and nitriles as the amination reagents has been developed. Various vicinal diamines were obtained in moderate to excellent yields under mild reaction conditions. Furthermore, this protocol could be applied in the late-stage modification of pharmaceuticals and natural products. Preliminary mechanistic studies suggested that this methodology may undergo a radical pathway followed by a Ritter-type reaction.

8.
Front Oncol ; 14: 1346964, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38482206

RESUMO

Pancreatoblastoma (PB) is a rare malignant pancreatic epithelial tumor that mostly occurs in children and occasionally occurs in adults. The tumor has acinar cell differentiation and squamous corpuscles/squamous epithelial islands, which are frequently separated by fibrous bundles. Familial adenomatous polyposis (FAP) is an autosomal dominant inherited disease characterized by the presence of numerous adenomatous polyps in the colon and rectum. Cases of pancreatoblastoma combined with familial adenomatous polyposis (FAP) are rarely reported. A review of a rare case of adult pancreatoblastoma with atypical histological morphology combined with familial adenomatous polyposis is presented herein. In this case, the patient was first diagnosed with familial adenomatous polyposis and subsequently found to have pancreatoblastoma 1 year and 3 months later. This suggests pancreatoblastoma may occur in patients with familial adenomatous polyposis or a family history of the condition, indicating a possible association between the two tumors. Therefore, pancreatoblastoma should be included in a differential diagnosis for FAP patients with a pancreatic mass. The final diagnosis of pancreatoblastoma depends on the pathological diagnosis. Acinar-like cells and squamous corpuscles/squamous epithelial cell islands under light microscopy are the key diagnostic points. This case report also can improve the awareness of clinicians, radiologists, and pathologists on the presence of rare tumor-adult pancreatoblastoma in patients with familial adenomatous polyposis.

9.
J Hazard Mater ; 469: 133932, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38484659

RESUMO

The extensive use of aluminum (Al) poses an escalating ecological risk to aquatic ecosystems. The epiphytic biofilm on submerged plant leaves plays a crucial role in the regulation nutrient cycling and energy flow within aquatic environments. Here, we conducted a mesocosm experiment aimed at elucidating the impact of different Al concentrations (0, 0.6, 1.2, 2.0 mg/L) on microbial communities in epiphytic biofilms on Vallisneria natans. At 1.2 mg/L, the highest biofilms thickness (101.94 µm) was observed. Al treatment at 2.0 mg/L significantly reduced bacterial diversity, while micro-eukaryotic diversity increased. Pseudomonadota and Bacteroidota decreased, whereas Cyanobacteriota increased at 1.2 mg/L and 2.0 mg/L. At 1.2 and 2.0 mg/L. Furthermore, Al at concentrations of 1.2 and 2.0 mg/L enhanced the bacterial network complexity, while micro-eukaryotic networks showed reduced complexity. An increase in positive correlations among microbial co-occurrence patterns from 49.51% (CK) to 57.05% (2.0 mg/L) was indicative of augmented microbial cooperation under Al stress. The shift in keystone taxa with increasing Al concentration pointed to alterations in the functional dynamics of microbial communities. Additionally, Al treatments induced antioxidant responses in V. natans, elevating leaf reactive oxygen species (ROS) content. This study highlights the critical need to control appropriate concentration Al concentrations to preserve microbial diversity, sustain ecological functions, and enhance lake remediation in aquatic ecosystems.


Assuntos
Hydrocharitaceae , Microbiota , Alumínio/toxicidade , Biofilmes , Folhas de Planta , Interações Microbianas
10.
Dig Liver Dis ; 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38320913

RESUMO

BACKGROUND AND AIMS: Giant esophageal leiomyoma usually requires a thoracotomy or thoracoscopic surgery, which is more invasive than an endoscopic treatment. The purpose of this study is to evaluate the efficacy and safety of piecemeal submucosal tunneling endoscopic resection (P-STER) for giant leiomyoma originating from the muscularis propria (MP) layer of the esophagus. METHODS: This is a retrospective study. Patients with giant esophageal leiomyoma (transverse diameter ≥ 3 cm) who underwent P-STER were enrolled from November 2012 to May 2023. Clinical data and results were investigated. RESULTS: A total of 16 patients were enrolled for analysis. The lesion mean transverse diameter and longitudinal diameter were 4.22 ± 1.20 cm and 6.20 ± 1.57 cm, respectively. Our mean operation time was 195.38 ± 84.99 min. The mean number of piecemeal resected was 4.31 ± 2.36. An adverse event noted was an esophageal fistula that occurred in one case (6.25%) and was treated conservatively. The mean length of hospital stay was around 11.81 ± 7.30 days. The mean total hospitalization cost was U.S. dollars (USD) $5976.50 ± 2866.39. No recurrence or metastasis was found during the follow-up period. CONCLUSIONS: P-STER can be an effective and safe treatment for giant leiomyoma originating from the MP layer of the esophagus.

11.
Eur J Med Chem ; 265: 116090, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38169272

RESUMO

The role of AXL in various oncogenic processes has made it an attractive target for cancer therapy. Currently, kinase selectivity profiles, especially circumventing MET inhibition, remain a scientific issue of great interest in the discovery of selective type II AXL inhibitors. Starting from a dual MET/AXL-targeted lead structure from our previous work, we optimized a 1,6-naphthyridinone series using molecular modeling-assisted compound design to improve AXL potency and selectivity over MET, resulting in the potent and selective type II AXL-targeted compound 25c. This showed excellent AXL inhibitory activity (IC50 = 1.1 nM) and 343-fold selectivity over the highly homologous kinase MET in biochemical assays. Moreover, compound 25c significantly inhibited AXL-driven cell proliferation, dose-dependently suppressed 4T1 cell migration and invasion, and induced apoptosis. Compound 25c also showed noticeable antitumor efficacy in a BaF3/TEL-AXL xenograft model at well-tolerated doses. Overall, this study presented a potent and selective type II AXL-targeted lead compound for further drug discovery.


Assuntos
Antineoplásicos , Inibidores de Proteínas Quinases , Humanos , Linhagem Celular Tumoral , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/química , Relação Estrutura-Atividade , Proliferação de Células , Modelos Moleculares , Antineoplásicos/farmacologia , Antineoplásicos/química , Estrutura Molecular
12.
Environ Pollut ; 344: 123301, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38190873

RESUMO

The widespread application of sulfonamide antibiotics in aquaculture has raised concerns about their adverse environmental impacts. Periphyton plays a crucial role in the aquatic ecosystem. In this study, we examined sulfamethoxazole (SMX) effects on the community structure and interactions of periphyton in simulated aquaculture water. Our findings indicated that the total biomass of periphyton decreased, while the biomass of periphytic algae and the secretion of extracellular polymeric substances (EPS) increased at 0.7 × 10-3 mg/L. Under higher SMX concentrations (5 mg/L and 10 mg/L), periphyton growth was severely inhibited, the microbial community structure of periphyton were sharply altered, characterized by the cyanobacteria growth suppression and decrease in the diversity index of community. Furthermore, elevated SMX concentrations (5 mg/L and 10 mg/L) increased the ratio of negative relationships from 45.4% to 49.4%, which suggested that high SMX concentrations promoted potential competition among microbes and disrupted the microbial food webs in periphyton. The absolute abundance of sul1 and sul2 genes in T2 and T3 groups were 2-3 orders of magnitude higher than those in control group after 30 days of SMX exposure, which elevated the risk of resistance gene enrichment and dissemination in the natural environment. The study contributes to our understanding of the detrimental effects of antibiotic pollution, which can induce changes in the structure and interaction relationship of microbial communities in aquaculture water.


Assuntos
Microbiota , Perifíton , Sulfametoxazol/toxicidade , Biomassa , Água , Antibacterianos/toxicidade , Aquicultura
13.
Gynecol Oncol ; 182: 156-167, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38266402

RESUMO

OBJECTIVE: This study explored promising prognostic and immune therapeutic candidate biomarkers for OC and determined the expression, prognostic value, and immune effects of UCHL3. METHODS: UCHL3 expression and clinical data were investigated using bioinformatic analysis. CCK8 and transwell assays were conducted to evaluate the impact of UCHL3 on proliferation and migration, and the effects of UCHL3 were further validated in a mouse model. Univariate and least absolute shrinkage and selection operator regression analyses were performed to construct a novel UCHL3-related prognostic risk model. Gene set enrichment analysis (GSEA) and immune analysis were performed to identify the significantly involved functions of UCHL3. Finally, bioinformatic analysis and immunohistochemistry were performed to explore the effect of UCHL3 on chemotherapy. RESULTS: UCHL3 expression was upregulated and associated with worse overall survival (OS) in OC. UCHL3 depletion repressed cell proliferation and migration both in vitro and in vivo. Furthermore, 237 genes were differentially expressed between the high and low UCHL3 expression groups. Subsequently, a UCHL3-related prognostic signature was built based on six prognostic genes (PI3, TFAP2B, MUC7, PSMA2, PIK3C2G, and NME1). Independent prognostic analysis suggested that age, tumor mutational burden, and RiskScore can be used as independent prognostic factors. The immune infiltration analysis and GSEA suggested that UCHL3 expression was related to the immune response. In addition, UCHL3 expression was higher in platinum-resistant OC patients than in platinum-sensitive patients. UCHL3 overexpression was associated with poorer OS. CONCLUSION: UCHL3 overexpression contributes to aggressive progression, poor survival, and chemoresistance in OC. Therefore, UCHL3 may be a candidate prognostic biomarker and potential target for controlling progression and platinum resistance in OC.


Assuntos
Neoplasias Ovarianas , Animais , Camundongos , Feminino , Humanos , Biomarcadores , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Agressão , Proliferação de Células , Biologia Computacional , Platina , Prognóstico , Ubiquitina Tiolesterase/genética
14.
Phytochemistry ; 218: 113958, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38154730

RESUMO

Six undescribed nordrimane sesquiterpene derivatives, salvirrane A-F (1-6), were isolated from the roots and rhizomes of Salvia castanea Diels f. tomentosa Stib. Comprehensive spectral analysis and a quantum chemical calculation strategy were employed to determine their structures. These compounds represent four previously unreported nordrimane carbon skeletal types in Salvia genus, including 15-nor-drimane, 11,15-di-nor-drimane, 14,15-di-nor-drimane, and 11,14,15-tri-nor-drimane sesquiterpenes. All compounds were evaluated for their cytotoxic activities against several human cancer cell lines (A549, H460, Hep3B, MCF7, PC3, and HeLa). The results showed that 3 exhibited low activity against MCF7 cells (IC50,72.72 ± 6.95 µM) and moderate activity against HeLa cells (IC50, 9.80 ± 0.64 µM). Moreover, the EdU (5-ethynyl-2'-deoxyuridine) assay demonstrates that 3 displays dose-dependent efficacy in suppressing the proliferation of HeLa cells. Network pharmacology and molecular docking technology implied that 3 may potentially bind to Src (proto-oncogene tyrosine-protein kinase) to exert anti-proliferative activity.


Assuntos
Antineoplásicos , Sesquiterpenos Policíclicos , Salvia , Sesquiterpenos , Humanos , Células HeLa , Simulação de Acoplamento Molecular , Sesquiterpenos/química , Antineoplásicos/farmacologia , Salvia/química , Estrutura Molecular
15.
Org Lett ; 25(51): 9191-9196, 2023 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-38114417

RESUMO

Herein, we report an unprecedented implementation of 3-halooxindoles as C-C-O three-atom components for (3+3) cycloaddition with pyridinium 1,4-zwitterionic thiolates, affording structurally diverse indolenine-fused 2H-1,4-oxathiines in moderate to high yields. A combined experimental and computational mechanistic study suggests that the reaction proceeds through addition of a S conjugate to the o-azaxylylene intermediate, followed by O-Michael addition and a sequential retro-Michael addition/pyridine extrusion pathway.

16.
Front Psychol ; 14: 1277188, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38023015

RESUMO

This research article focuses on the significance of Workplace Civility, defined as the respectful and courteous behavior exhibited by individuals toward their colleagues in the workplace. The primary objective of this study is to conduct a systematic review and a meta-analysis that synthesizes existing research by: (1) identifying operational definitions of the construct, (2) underlying the strongest correlations with other variables, (3) summarizing the effective strategies for promoting Workplace Civility, and (4) highlighting gaps in the literature, using the theory-characteristics-context-methodology (TCCM) framework. Multiple databases were meticulously searched, yielding 691 results, and ultimately 51 documents were included in the systematic review final sample following the application of predefined exclusion criteria. Then, a meta-analysis has been conducted including those studies with sufficient statistical data (k = 24) which allowed us to calculate 45 Effect Sizes. The review findings expose a notable dearth of research on Workplace Civility when compared to studies on incivility. This dearth highlights the pressing need for additional research endeavors to precisely define Workplace Civility, establish a robust theoretical framework, and develop reliable scales for its measurement. Related to the desirable correlates, organizational commitment, job satisfaction and mental health showed a high ES value, and for undesirable correlates, intention to quit showed a high ES value, while Emotional exhaustion only reached a medium ES value and physical symptoms showed a low ES value. Importantly, this study emphasizes that fostering civility in the workplace can yield significant benefits such as improved physical and mental well-being for workers, reduced burnout, and absenteeism rates. Thus, the promotion of civility in the workplace not only leads to healthier organizations but also enhances cost-efficiency, effectively averting the loss of both human and economic capital.

18.
mBio ; : e0168823, 2023 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-37882780

RESUMO

The segmented negative-strand RNA viruses (sNSVs) include highly pathogenic human and animal viruses such as Lassa virus (LASV), severe fever with thrombocytopenia syndrome virus (SFTSV), and influenza A virus (IAV). One of the conserved mechanisms at the stage of genome transcription of sNSVs is the cap-snatching process, providing druggable targets for the development of antivirals. SFTSV is an emerging tick-borne sNSV that causes severe hemorrhagic fever with a high fatality rate of 12%-50%. Here, we determined the correlation between death outcome and downregulation of the WNT-CTNNB1 signaling pathway through transcriptomic analysis of blood samples collected from SFTS patients. We further demonstrated that SFTSV affected this pathway by downregulating the mRNA levels of a series of pathway-related genes, including CTNNB1. Loss-of-function mutations or inhibitors targeting SFTSV cap-snatching activity effectively alleviated the inhibition of the WNT-CTNNB1 signaling pathway. Exogenous activation of the WNT-CTNNB1 signaling pathway enhanced SFTSV replication, while inhibition of this pathway reduced SFTSV replication. Treatment with a WNT-CTNNB1 signaling pathway inhibitor attenuated viral replication and decreased fatality in mice. Notably, downregulation of the WNT-CTNNB1 signaling pathway was also observed for other sNSVs, including LASV and IAV. These results suggested that RNAs related to the WNT-CTNNB1 signaling pathway might be utilized as a primer "pool" in a cap-snatching manner for viral transcription, which provides effective targets for the development of broad-spectrum antivirals against sNSVs.IMPORTANCEOne of the conserved mechanisms at the stage of genome transcription of segmented negative-strand RNA viruses (sNSVs) is the cap-snatching process, which is vital for sNSVs transcription and provides drugable targets for the development of antivirals. However, the specificity of RNAs snatched by sNSV is still unclear. By transcriptomics analysis of whole blood samples from SFTS patients, we found WNT-CTNNB1 signaling pathway was regulated according to the course of the disease. We then demonstrated that L protein of severe fever with thrombocytopenia syndrome virus (SFTSV) could interact with mRNAs of WNT-CTNNB1 signaling pathway-related gene, thus affecting WNT-CTNNB1 signaling pathway through its cap-snatching activity. Activation of WNT-CTNNB1 signaling pathway enhanced SFTSV replication, while inhibition of this pathway decreased SFTSV replication in vitro and in vivo. These findings suggest that WNT-associated genes may be the substrate for SFTSV "cap-snatching", and indicate a conserved sNSVs replication mechanism involving WNT-CTNNB1 signaling.

19.
Int Immunopharmacol ; 125(Pt A): 111094, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37871379

RESUMO

BACKGROUND: The treatment of nasopharyngeal carcinoma (NPC) is currently based on concurrent chemoradiotherapy. The prognosis of early NPC is better, while the prognosis of advanced NPC is poor. Immunotherapy is becoming increasingly commonly employed in clinical practice as a new strategy for treating malignant tumors. It has shown promising results in the treatment of certain malignant tumors, making it a current clinical research hotspot. METHODS: This review summarizes the current immunotherapy on NPC, highlighting the application of immunotherapy and radiotherapy in the treatment of NPC. RESULTS: X-rays can either increase or suppress anti-tumor immune responses through various pathways and mechanisms. Immune checkpoint inhibitors can usually enhance X-ray-induced anti-tumor immune responses. Detecting the immune checkpoint markers and tumor mutation markers, and the functional status of effector cells in patients can aid in the development of individualized treatment that improves the treatment efficacy with reducing drug resistance and adverse reactions. The development of a multivalent vaccine for NPC will help improve the efficacy of the vaccine. Combining techniques that increase the tumor antigens release, such as radiotherapy and oncolytic virus vaccines, may enhance the ability of the immune response. CONCLUSIONS: To shed further light on the application of immunotherapy in NPC, large pooled studies must accumulate sufficient cases with detailed exposure data.


Assuntos
Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/tratamento farmacológico , Neoplasias Nasofaríngeas/radioterapia , Neoplasias Nasofaríngeas/tratamento farmacológico , Imunoterapia/métodos , Quimiorradioterapia , Biomarcadores Tumorais
20.
Metabolites ; 13(9)2023 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-37755284

RESUMO

Light quality and sucrose-induced osmotic stress are known to cause anthocyanin synthesis in detached Lycium ruthenicum leaves. To identify the mechanisms by which the kind of light quality and sucrose concentration are induced, here, we conducted transcriptome sequencing in detached L. ruthenicum leaves treated with different qualities of light and sucrose concentrations. Leaves treated with blue light or sucrose showed a significantly increased total anthocyanins content compared to those treated with white light. Delphinidin-3-O-rutinoside and delphinidin-3-O-glucoside production were differentially regulated by the BL(-S), BL(+S), and WL(+S) treatments. The structural genes CHS, CHI, F3'H, F3'5'H, ANS, and UFGT were significantly up-regulated in leaves treated with blue light or sucrose. Leaves treated with blue light additionally showed up-regulation of the light photoreceptors CRY1, PIF3, COP1, and HY5. The anthocyanin-related genes NCED1, PYR/PYL, PP2C, SnRK2, and ABI5 were significantly up-regulated in leaves treated with sucrose, promoting adaptability to sucrose osmotic stress. Co-expression and cis-regulatory analyses suggested that HY5 and ABI5 could regulate LrMYB44 and LrMYB48 through binding to the G-box element and ABRE element, respectively, inducing anthocyanin synthesis in response to blue light or sucrose treatment. Candidate genes responsive to blue light or sucrose osmotic stress in the anthocyanin biosynthesis pathway were validated through quantitative reverse transcription PCR. These findings deepen our understanding of the mechanisms by which blue light and sucrose-induced osmotic stress regulate anthocyanin synthesis, providing valuable target genes for the future improvement in anthocyanin production in L. ruthenicum.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...