Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 434
Filtrar
1.
Pestic Biochem Physiol ; 204: 106090, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39277403

RESUMO

Chilo suppressalis, a critical rice stem borer pest, poses significant challenges to rice production due to its overlapping generations and irregular developmental duration. These characteristics complicate pest management strategies. According to the dynamic analysis of the overwintering adults of C. suppressalis in fields, it indicates that the phenomenon of irregular development of C. suppressalis exists widely and continuously. This study delves into the potential role of the Broad-Complex (Br-C) gene in the developmental duration of C. suppressalis. Four isoforms of Br-C, named CsBr-C Z1, CsBr-C Z2, CsBr-C Z4, and CsBr-C Z7, were identified. After CsBr-Cs RNAi, the duration of larva development spans extended obviously. And, the average developmental duration of dsCsBr-Cs feeding individuals increased obviously. Meanwhile, the average developmental duration of the dsCsBr-C Z2 feeding group was the longest among all the RNAi groups. After dsCsBr-Cs feeding continuously, individuals pupated at different instars changed obviously: the proportion of individuals pupated at the 5th instar decreased and pupated at the 7th instar or higher increased significantly. Moreover, the pupation rate of dsCsBr-Cs (except dsCsBr-C Z7) were significantly lower than that of dsGFP. The same results were obtained from the mutagenesis in CsBr-C genes mediated by CRISPR/Cas9. The average developmental duration of CsBr-Cs knockout individuals was significantly prolonged. And, the instar of pupation in knockout individuals was also delayed significantly. In conclusion, this work showed that CsBr-Cs played a crucial role in pupal commitment and affected the developmental duration of C. suppressalis significantly.


Assuntos
Proteínas de Insetos , Larva , Mariposas , Interferência de RNA , Animais , Mariposas/crescimento & desenvolvimento , Mariposas/genética , Larva/crescimento & desenvolvimento , Larva/genética , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Pupa/crescimento & desenvolvimento , Pupa/genética , Oryza/parasitologia , Oryza/crescimento & desenvolvimento
2.
Int Immunopharmacol ; 142(Pt B): 113106, 2024 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-39288623

RESUMO

Clear cell renal cell carcinoma (ccRCC) represents a prevalent malignancy of the urinary system. Despite the integration of immune checkpoint inhibitors (ICIs) into the treatment paradigm for advanced RCC, resistance to immunotherapy has emerged as a pivotal determinant impacting the clinical outlook of ccRCC. Accumulating evidence underscores the pivotal role of immune evasion-related genes and pathways in enabling tumor escape from host immune surveillance, consequently influencing patients' responsiveness to immunotherapy. Nonetheless, the clinical relevance of immune evasion-related genes in ccRCC patients undergoing immunotherapy remains inadequately understood. In this study, we aggregated RNA sequencing and clinical data from ccRCC patients across three cohorts: the Cancer Genome Atlas (TCGA), CheckMate cohorts, and the JAVELIN Renal 101 trial. Leveraging a curated immune evasion-related gene set from Lawson et al., we employed the LASSO algorithm and Cox regression analysis to identify eight genes (LPAR6, RGS5, NFYC, PCDH17, CENPW, CNOT8, FOXO3, SNRPB) significantly associated with immune therapy prognosis (HR, 3.57; 95 % CI, 2.38-5.35; P<0.001). A predictive algorithm developed utilizing these genes exhibited notable accuracy in forecasting patients' progression-free survival in the training set (AUC, 0.835). Furthermore, stratification of patients by risk score revealed discernible differences in immunotherapy response and tumor microenvironment. In summary, we present a prognostic model intricately linked with immune status and treatment response. For ccRCC patients undergoing immunotherapy, this approach holds promise in aiding clinical decision-making by providing more precise and tailored treatment recommendations.

3.
Anal Chem ; 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39259665

RESUMO

Influenza A virus (IAV) can cause infectious respiratory diseases in humans and animals. IAVs mutate rapidly through antigenic drift and shift, resulting in the emergence of numerous IAV subtypes and significant challenges for IAV detection. Therefore, achieving the simultaneous detection of multiple IAVs is crucial. In this work, three specific aptamers targeting the hemagglutination (HA) protein of the influenza A H5N1, H7N9, and H9N2 viruses were screened using a multichannel magnetic microfluidic chip. The aptamers exhibit nanomolar affinity and excellent specificity for the HA protein of H5N1, H7N9, and H9N2 viruses. Furthermore, three specific aptamers were truncated and labeled with different fluorescence markers to realize fluorescence quantitative detection of influenza A H5N1, H7N9, and H9N2 viruses through an aptamer sandwich assay in 1 h. The limit of detection (LOD) of the developed method is 0.38 TCID50/mL for the H5N1 virus, 0.75 TCID50/mL for the H7N9 virus, and 1.14 TCID50/mL for the H9N2 virus. The detection method has excellent specificity, strong anti-interference ability, and good reproducibility. This work provides a sensitive quantitative detection method for the H5N1, H7N9, and H9N2 viruses, enabling quantitative fluorescence detection for multiple IAV subtypes.

4.
Anal Methods ; 16(35): 5999-6010, 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39171437

RESUMO

Eliminating errors in next-generation sequencing has proven to be challenging. Here we present a novel strategy for DNA sequencing, called correctable two-color fluorogenic DNA decoding sequencing, which can significantly improve sequencing accuracy and throughput by employing a dual-nucleotide addition combined with fluorogenic sequencing-by-synthesis (SBS) chemistry. This sequencing method involves introducing a mixture of natural nucleotide X, labeled unblocked nucleotide X', 3' blocked nucleotide Y*, and labeled 3' blocked nucleotide Y* into each reaction cycle. By cyclically interrogating a template twice with different nucleotide combinations, two sets of base-encoding are sequentially obtained, enabling accurate deduction of base sequence. We demonstrate the remarkable efficacy of this approach in detecting and correcting sequencing errors, achieving a theoretical error rate of 0.0005%, which is twice as accurate as Sanger sequencing. Furthermore, we show the capability to detect known mutation sites using information from only a single sequencing run. The correctable two-color fluorogenic DNA decoding sequencing approach should enable accurate identification of extremely rare genomic variations in diverse applications in biology and medicine.


Assuntos
Sequenciamento de Nucleotídeos em Larga Escala , Análise de Sequência de DNA , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Análise de Sequência de DNA/métodos , Corantes Fluorescentes/química , DNA/genética , DNA/química , Humanos , Mutação
5.
Anal Bioanal Chem ; 2024 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-39158632

RESUMO

Vaccinia virus (VACV)-induced cell migration is thought to be closely related to the rapid transmission of viral infection in the body. The limited studies are mainly based on scratch assay using traditional cell culture techniques, which inevitably ignores the influences of extracellular microenvironment. Physical confinement, inherently presenting in vivo, has proven to be a critical extern cue in modulating migration behaviors of multiple cells, while its impacts on VACV-induced cell motility remain unclear. Herein, we developed a migration assay microchip featuring confined microchannel array to investigate the effect of physical confinement on infected cell morphology and motility during VACV infection. Results showed that different from the random cell migration observed in traditional scratch assay on planar substrate, VACV-infected cells exhibited accelerated directionally persistent migration under confinement microenvironment. Moreover, single-directed elongated dominant lamella appeared to contrast distinctly with multiple protrusions stretched in random directions under unconfined condition. Additionally, the Golgi complex tended to relocate behind the nucleus confined within the microchannel axis compared to the classical reorientation pattern. These differences in characteristic subcellular architecture and organelle reorientation of migrating cells revealed cell biological mechanisms underlying altered migration behavior. Collectively, our study demonstrates that physical confinement acting as a guidance cue has profound impacts on VACV-induced migration behaviors, which provides new insight into cell migration behavior and viral rapid spread during VACV infection.

6.
ACS Nano ; 18(37): 25893-25905, 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39214619

RESUMO

After entering host cells by endocytosis, influenza A virus (IAV) is transported along microfilaments and then transported by dynein along microtubules (MTs) to the perinuclear region for genome release. Understanding the mechanisms of dynein-driven transport is significant for a comprehensive understanding of IAV infection. In this work, the roles of dynactin in dynein-driven transport of IAV were quantitatively dissected in situ using quantum dot-based single-virus tracking. It was revealed that dynactin was essential for dynein to transport IAV toward the nucleus. After virus entry, virus-carrying vesicles bound to dynein and dynactin before being delivered to MTs. The attachment of dynein to the vesicles was dependent on dynactin and its subunits, p150Glued and Arp1. Once viruses reached MTs, dynactin-assisted dynein initiates retrograde transport of IAV. Importantly, the retrograde transport of viruses could be initiated at both plus ends (32%) and other regions on MTs (68%). Subsequently, dynactin accompanied and assisted dynein to persistently transport the virus along MTs in the retrograde direction. This study revealed the dynactin-dependent dynein-driven transport process of IAV, enhancing our understanding of IAV infection and providing important insights into the cell's endocytic transport mechanism.


Assuntos
Complexo Dinactina , Dineínas , Vírus da Influenza A , Pontos Quânticos , Complexo Dinactina/metabolismo , Dineínas/metabolismo , Pontos Quânticos/química , Pontos Quânticos/metabolismo , Humanos , Vírus da Influenza A/metabolismo , Transporte Biológico , Animais , Microtúbulos/metabolismo , Cães , Células Madin Darby de Rim Canino , Células A549
7.
Anal Methods ; 16(31): 5403-5411, 2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-39036899

RESUMO

In recent years, the cargo profiles of extracellular vesicles (EVs), which were inherited from their parent cells, have emerged as a reliable biomarker for liquid biopsy (LB) in disease diagnosis, prognosis, and treatment monitoring. EVs secreted by different cells exhibit distinct characteristics, particularly in terms of disease diagnosis and prediction. However, currently available techniques for the quantitative analysis of EV cargoes, including enzyme-linked immunosorbent assay (ELISA), cannot specifically identify the cellular origin of EVs, thus seriously affecting the accuracy of EV-based liquid biopsy. In light of this, we here developed ultrabright fluorescent nanosphere (FNs)-based test strips which have the unique capability to specifically assess the levels of PD-L1-positive EVs (PD-L1+ EVs) derived from both tumor cells and immune cells in bodily fluids. The levels of PD-L1+ EV subpopulations in human saliva were quantified using the ultrabright fluorescent nanosphere-based test strips with more convenience and higher efficiency (detection time <30 min). Results demonstrated that the fluorescence intensity of the test line exhibited a good linear relationship respectively with the PD-L1 levels of tumor cell- (R2 = 0.993) and immune cell-derived EVs (R2 = 0.982) in human saliva. By assessing the levels of PD-L1+ EV subpopulations, our test strips hold immense potential for advancing the application of PD-L1+ EV subpopulation-based predictions in tumor diagnosis and prognosis evaluation. In summary, by integrating the benefits of FNs and lateral flow chromatography, we here provide a strategy to accurately measure the cargo levels of EVs originating from diverse cell sources in bodily fluids.


Assuntos
Vesículas Extracelulares , Nanosferas , Humanos , Vesículas Extracelulares/química , Nanosferas/química , Saliva/química , Antígeno B7-H1/metabolismo , Antígeno B7-H1/análise , Corantes Fluorescentes/química , Biópsia Líquida/métodos , Fitas Reagentes/química , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral
8.
J Natl Cancer Cent ; 4(1): 6-13, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-39036384

RESUMO

Renal cancer is one of the most common malignancies of the urinary system, and the number of deaths continues to increase. The standardized management of the diagnosis and treatment of renal cancer is challenging due to the great differences in the diagnosis and treatment of renal cancer in different regions. The Renal Cancer Expert Committee of the National Cancer Quality Control Center (NCQCC) identified a lack of authoritative quality control standards as an opportunity to utilize its multidisciplinary membership to improve the standardized diagnosis and treatment of renal cancer. The Renal Cancer Expert Committee of the NCQCC aims to promote quality control and national standardization, uniformity, and normalization of renal cancer diagnosis and treatment, which ultimately improved the survival rate and quality of life of renal cancer patients. A panel of experts with renal cancer surgery, renal cancer medicine, medical imaging, pathology and radiotherapy were drawn together and determined the quality control standards for the standardized diagnosis and treatment of renal cancer. The Indices includes 20 items that cover all key areas in the diagnosis and treatment of renal cancer, such as standard diagnosis, surgery treatment, systemic treatment, and prognostic evaluation.

9.
Opt Express ; 32(12): 21269-21280, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38859485

RESUMO

The projection of fringes plays an essential role in many applications, such as fringe projection profilometry and structured illumination microscopy. However, these capabilities are significantly constrained in environments affected by optical scattering. Although recent developments in wavefront shaping have effectively generated high-fidelity focal points and relatively simple structured images amidst scattering, the ability to project fringes that cover half of the projection area has not yet been achieved. To address this limitation, this study presents a fringe projector enabled by a neural network, capable of projecting fringes with variable periodicities and orientation angles through scattering media. We tested this projector on two types of scattering media: ground glass diffusers and multimode fibers. For these scattering media, the average Pearson's correlation coefficients between the projected fringes and their designed configurations are 86.9% and 79.7%, respectively. These results demonstrate the effectiveness of the proposed neural network enabled fringe projector. This advancement is expected to broaden the scope of fringe-based imaging techniques, making it feasible to employ them in conditions previously hindered by scattering effects.

10.
Cancer Immunol Immunother ; 73(7): 130, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38748254

RESUMO

Immune surveillance and chemotherapy sensitivity play critical functions in the tumorigenesis of breast cancer (BC). Emerging findings have indicated that circular RNA (circRNA) and N6-methyladenosine (m6A) both participate in the BC tumorigenesis. Here, present study aimed to investigate the roles of m6A-modified circATAD2 on BC and explore better understanding for BC precision therapeutic. Results reported that m6A-modifid circRNA (m6A-circRNA) microarray revealed the m6A-circRNA landscape in BC. M6A-modifid circATAD2 upregulated in BC samples and was closely correlated to poor prognosis. Functionally, circATAD2 promoted the immune evasion of BC cells and reduced the CD8+ T cells' killing effect. Mechanistically, MeRIP-seq unveiled the m6A modification in the 3'-UTR of PD-L1 mRNA, which was bound by circATAD2 and recognized by m6A reader IGF2BP3 to enhance PD-L1 mRNA stability and expression. In summary, these findings revealed the circATAD2/m6A/IGF2BP3/PD-L1 axis in BC immune surveillance, suggesting the potential that circATAD2 as a potential target for PD-L1-mediated BC.


Assuntos
Antígeno B7-H1 , Neoplasias da Mama , Linfócitos T CD8-Positivos , Vigilância Imunológica , RNA Circular , Proteínas de Ligação a RNA , Animais , Feminino , Humanos , Camundongos , Adenosina/análogos & derivados , Adenosina/metabolismo , Antígeno B7-H1/metabolismo , Antígeno B7-H1/genética , Neoplasias da Mama/imunologia , Neoplasias da Mama/genética , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Prognóstico , RNA Circular/genética , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/genética , Metilação de RNA/genética
11.
Cell Mol Life Sci ; 81(1): 232, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38780644

RESUMO

Ubiquitin-proteasome system dysfunction triggers α-synuclein aggregation, a hallmark of neurodegenerative diseases, such as Parkinson's disease (PD). However, the crosstalk between deubiquitinating enzyme (DUBs) and α-synuclein pathology remains unclear. In this study, we observed a decrease in the level of ubiquitin-specific protease 14 (USP14), a DUB, in the cerebrospinal fluid (CSF) of PD patients, particularly females. Moreover, CSF USP14 exhibited a dual correlation with α-synuclein in male and female PD patients. To investigate the impact of USP14 deficiency, we crossed USP14 heterozygous mouse (USP14+/-) with transgenic A53T PD mouse (A53T-Tg) or injected adeno-associated virus (AAV) carrying human α-synuclein (AAV-hα-Syn) in USP14+/- mice. We found that Usp14 deficiency improved the behavioral abnormities and pathological α-synuclein deposition in female A53T-Tg or AAV-hα-Syn mice. Additionally, Usp14 inactivation attenuates the pro-inflammatory response in female AAV-hα-Syn mice, whereas Usp14 inactivation demonstrated opposite effects in male AAV-hα-Syn mice. Mechanistically, the heterodimeric protein S100A8/A9 may be the downstream target of Usp14 deficiency in female mouse models of α-synucleinopathies. Furthermore, upregulated S100A8/A9 was responsible for α-synuclein degradation by autophagy and the suppression of the pro-inflammatory response in microglia after Usp14 knockdown. Consequently, our study suggests that USP14 could serve as a novel therapeutic target in PD.


Assuntos
Calgranulina A , Calgranulina B , Camundongos Transgênicos , Doença de Parkinson , Ubiquitina Tiolesterase , alfa-Sinucleína , Animais , Feminino , Humanos , Masculino , Camundongos , alfa-Sinucleína/metabolismo , alfa-Sinucleína/genética , Calgranulina A/metabolismo , Calgranulina A/genética , Calgranulina B/metabolismo , Calgranulina B/genética , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Doença de Parkinson/metabolismo , Doença de Parkinson/genética , Doença de Parkinson/patologia , Ubiquitina Tiolesterase/metabolismo , Ubiquitina Tiolesterase/genética , Ubiquitina Tiolesterase/deficiência
13.
Antonie Van Leeuwenhoek ; 117(1): 74, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38691182

RESUMO

A Gram-stain positive, aerobic, alkalitolerant and halotolerant bacterium, designated HH7-29 T, was isolated from the confluence of the Fenhe River and the Yellow River in Shanxi Province, PR China. Growth occurred at pH 6.0-12.0 (optimum, pH 8.0-8.5) and 15-40℃ (optimum, 32℃) with 0.5-24% NaCl (optimum, 2-9%). The predominant fatty acids (> 10.0%) were iso-C15:0 and anteiso-C15:0. The major menaquinones were MK-7 and MK-8. The polar lipids were phosphatidylglycerol, diphosphatidylglycerol and two unidentified phospholipids. Phylogenetic analyses based on the 16S rRNA gene sequence revealed that strain HH7-29 T was a member of the genus Jeotgalibacillus, exhibiting high sequence similarity to the 16S rRNA gene sequences of Jeotgalibacillus alkaliphilus JC303T (98.4%), Jeotgalibacillus salarius ASL-1 T (98.1%) and Jeotgalibacillus alimentarius YKJ-13 T (98.1%). The genomic DNA G + C content was 43.0%. Gene annotation showed that strain HH7-29 T had lower protein isoelectric points (pIs) and possessed genes related to ion transport and organic osmoprotectant uptake, implying its potential tolerance to salt and alkali. The average nucleotide identity, digital DNA-DNA hybridization values, amino acid identity values, and percentage of conserved proteins values between strain HH7-29 T and its related species were 71.1-83.8%, 19.5-27.4%, 66.5-88.4% and 59.8-76.6%, respectively. Based on the analyses of phenotypic, chemotaxonomic, phylogenetic and genomic features, strain HH7-29 T represents a novel species of the genus Jeotgalibacillus, for which the name Jeotgalibacillus haloalkalitolerans sp. nov. is proposed. The type strain is HH7-29 T (= KCTC 43417 T = MCCC 1K07541T).


Assuntos
Composição de Bases , DNA Bacteriano , Ácidos Graxos , Filogenia , RNA Ribossômico 16S , Rios , RNA Ribossômico 16S/genética , China , Rios/microbiologia , DNA Bacteriano/genética , Ácidos Graxos/análise , Cloreto de Sódio/metabolismo , Técnicas de Tipagem Bacteriana , Fosfolipídeos/análise , Análise de Sequência de DNA , Hibridização de Ácido Nucleico
14.
J Phys Chem Lett ; 15(21): 5594-5599, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38755539

RESUMO

In recent years, silver nanoparticles (Ag NPs) have been used as positive electrode material for zinc/silver batteries, and the silver oxides formed during the charging process determine the discharge performance of batteries. Therefore, it is important to study the oxidation behavior of Ag NPs in alkaline solution. Single-nanoparticle collision is an important tool for analyzing oxidation behavior of individual nanoparticles. Based on thermodynamic information from collision events, it is known that oxidation products are potential-dependent and size-dependent. Based on dynamic information, including collisional peak shapes and duration time, it was observed that the Ag NP collision oxidation process changed from stepwise oxidation to direct oxidation as the potential increased or size decreased. This work provides guidance for application of Ag NPs in zinc/silver batteries and proposed a strategy for oxidation behavior of individual NP that could be tracked in situ through an all-encompassing view of thermodynamic and dynamic information.

15.
Anal Chem ; 96(16): 6195-6201, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38607805

RESUMO

Single particle collision is an important tool for size analysis at the individual particle level; however, due to complex dynamic behaviors of nanoparticles on the surface of an electrode, the accuracy of size discrimination is limited. A silver (Ag) nanoparticle (NP) was chosen as the research target, and the dynamic behavior of Ag NPs was simplified by enhancing adsorption between Ag NP and Au ultramicroelectrode (UME) in alkaline media. Immediately after, accurate dynamic and thermodynamic information on single Ag NP was accurately extracted from collision events, including current intensity, transferred charge, and duration time. On the basis that there were differences between parameters of different-sized Ag NPs, multiparameter size discrimination was proposed, which improved the accuracy compared to single-parameter discrimination. More intriguingly, multiparameter analysis was combined with artificial intelligence, a tool adept at processing multidimensional data, for the first time. Finally, artificial intelligence-assisted multiparameter size discrimination was successfully used to intelligently distinguish mixed Ag NPs, with an optimal accuracy of more than 95%. To sum up, the artificial intelligence-assisted multiparameter method showed an excellent ability to quickly achieve the most accurate size discrimination of nanoparticles at the level of individual particle and provide an effective guidance for the application of nanoparticles.

16.
Pestic Biochem Physiol ; 200: 105836, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38582598

RESUMO

The striped stem borer, Chilo suppressalis (Walker), a notorious pest infesting rice, has evolved a high level of resistance to many commonly used insecticides. In this study, we investigate whether tyrosine hydroxylase (TH), which is required for larval development and cuticle tanning in many insects, could be a potential target for the control of C. suppressalis. We identified and characterized the full-length cDNA (CsTH) of C. suppressalis. The complete open reading frame of CsTH (MW690914) was 1683 bp in length, encoding a protein of 560 amino acids. Within the first to the sixth larval instars, CsTH was high in the first day just after molting, and lower in the ensuing days. From the wandering stage to the adult stage, levels of CSTH began to rise and reached a peak at the pupal stage. These patterns suggested a role for the gene in larval development and larval-pupal cuticle tanning. When we injected dsCsTH or 3-iodotyrosine (3-IT) as a TH inhibitor or fed a larva diet supplemented with 3-IT, there were significant impairments in larval development and larval-pupal cuticle tanning. Adult emergence was severely impaired, and most adults died. These results suggest that CsTH might play a critical role in larval development as well as larval-pupal tanning and immunity in C. suppressalis, and this gene could form a potential novel target for pest control.


Assuntos
Inseticidas , Mariposas , Oryza , Animais , Larva/genética , Tirosina 3-Mono-Oxigenase/genética , Tirosina 3-Mono-Oxigenase/metabolismo , Pupa , Mariposas/metabolismo , Oryza/metabolismo
17.
Chem Biol Interact ; 393: 110947, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38479716

RESUMO

In this study, twenty-nine coumarin-3-sulfonamide derivatives, twenty-seven of which are original were designed and synthesized. Cytotoxicity assay indicated that most of these derivatives exhibited moderated to good potency against A549 cells. Among them, compound 8q showed potent inhibition against the four tested cancer cell lines, especially A549 cells with IC50 value of 6.01 ± 0.81 µM, and much lower cytotoxicity on the normal cells was observed compared to the reference compounds. Bioinformatics analysis revealed human carbonic anhydrase IX (CAIX) was highly expressed in lung adenocarcinoma (LUAD) and associated with poor prognosis. The inhibitory activity of compound 8q against CAIX was assessed by using molecular docking and molecular dynamics simulations, which revealed prominent interactions of both compound 8q and CAIX at the active site and their high affinity. The results of ELISA assays verified that compound 8q possessed strong inhibitory activity against CAIX and high subtype selectivity, and could also down-regulate the expression of CAIX in A549 cells. Furthermore, the significant inhibitory effects of compound 8q on the migration and invasion of A549 cells were also found. After treatment with compound 8q, intracellular reactive oxygen species (ROS) levels increased and mitochondrial membrane potential (MMP) decreased. Mechanistic investigation using western blotting revealed compound 8q exerted the anti-migrative and anti-invasive effects probably through mitochondria-mediated PI3K/AKT pathway by targeting CAIX. In summary, coumarin-3-sulfonamide derivatives were developed as potential and effective CAIX inhibitors, which were worthy of further investigation.


Assuntos
Inibidores da Anidrase Carbônica , Cumarínicos , Humanos , Anidrase Carbônica IX , Simulação de Acoplamento Molecular , Cumarínicos/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Antígenos de Neoplasias/metabolismo , Sulfonamidas/farmacologia , Relação Estrutura-Atividade , Estrutura Molecular
18.
Small ; 20(28): e2310795, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38501992

RESUMO

Developing the second near-infrared (NIR-II) photoacoustic (PA) agent is of great interest in bioimaging. Ag2Se quantum dots (QDs) are one kind of potential probe for applications in NIR-II photoacoustic imaging (PAI). However, the surfaces with excess anions of Ag2Se QDs, which increase the probability of nonradiative transitions of excitons benefiting PA imaging, are not conducive to binding electron donor ligands for potential biolabeling and imaging. In this study, Staphylococcus aureus (S. aureus) cells are driven for the biosynthesis of Ag2Se QDs with catalase (CAT). Biosynthesized Ag2Se (bio-Ag2Se-CAT) QDs are produced in Se-enriched environment of S. aureus and have a high Se-rich surface. The photothermal conversion efficiency of bio-Ag2Se-CAT QDs at 808 and 1064 nm is calculated as 75.3% and 51.7%, respectively. Additionally, the PA signal responsiveness of bio-Ag2Se-CAT QDs is ≈10 times that of the commercial PA contrast agent indocyanine green. In particular, the bacterial CAT is naturally attached to bio-Ag2Se-CAT QDs surface, which can effectively relieve tumor hypoxia. The bio-Ag2Se-CAT QDs can relieve heat-initiated oxidative stress while undergoing effective photothermal therapy (PTT). Such biosynthesis method of NIR-II bio-Ag2Se-CAT QDs opens a new avenue for developing multifunctional nanomaterials, showing great promise for PAI, hypoxia alleviation, and PTT.


Assuntos
Catalase , Técnicas Fotoacústicas , Terapia Fototérmica , Pontos Quânticos , Staphylococcus aureus , Pontos Quânticos/química , Técnicas Fotoacústicas/métodos , Catalase/metabolismo , Catalase/química , Animais , Compostos de Prata/química , Humanos , Raios Infravermelhos , Camundongos , Selênio/química
19.
Chem Commun (Camb) ; 60(20): 2772-2775, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38353965

RESUMO

To accelerate the discovery of high-affinity aptamers, a magnetically activated continuous deflection (MACD) chip was designed. The MACD chip could achieve dynamic selection in a continuous flow, which meant that the binding and separation were carried out consecutively. Dynamic selection could make selection efficient. Low-affinity sequences could be eluted in time and high-affinity sequences could be enriched via dynamic selection. The stringency of the conditions could be further increased by lowering the target concentration in the dynamic selection. Finally, a C.al3 aptamer with high-affinity and high-specificity for Candida albicans (C. albicans) was obtained through six rounds of selection. Its dissociation constant (Kd) was 7.9 nM. This demonstrated that dynamic selection using a MACD chip was an effective method for high-affinity aptamer selection.


Assuntos
Aptâmeros de Nucleotídeos , Microfluídica , Microfluídica/métodos , Técnica de Seleção de Aptâmeros/métodos , Análise de Sequência com Séries de Oligonucleotídeos
20.
Front Mol Neurosci ; 17: 1333842, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38419796

RESUMO

Oxaliplatin, a platinum-based chemotherapy drug, causes neuropathic pain, yet effective pharmacological treatments are lacking. Previously, we showed that tetrandrine (TET), with anti-inflammatory properties, reduces mechanical allodynia in nerve-injured mice. This study explores the effect of TET on oxaliplatin-induced mechanical allodynia and gene changes in mice. Male C57BL/6J mice received oxaliplatin intraperitoneally to induce mechanical allodynia. Post-treatment with TET or vehicle, the mechanical withdrawal threshold (WMT) was assessed using von Frey filaments. TET alleviated oxaliplatin-induced mechanical allodynia. RNA sequencing identified 365 differentially expressed genes (DEGs) in the Control vs. Oxaliplatin group and 229 DEGs in the Oxaliplatin vs. TET group. Pearson correlation analysis of co-regulated DEGs and inflammation-related genes (IRGs) revealed 104 co-regulated inflammation-related genes (Co-IRGs) (|cor| > 0.8, P < 0.01). The top 30 genes in the PPI network were identified. Arg2, Cxcl12, H2-Q6, Kdr, and Nfkbia were highlighted based on ROC analysis. Subsequently, Arg2, Cxcl12, Kdr, and Nfkbia were further verified by qRCR. Immune infiltration analysis indicated increased follicular CD4 T cell infiltration in oxaliplatin-treated mice, reduced by TET. Molecular docking showed strong binding affinity between TET and proteins encoded by Arg2, Cxcl12, Kdr, and Nfkbia. In summary, TET may alleviate oxaliplatin-induced peripheral neuropathy in clinical conditions.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA