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1.
Biomed Opt Express ; 15(5): 2811-2831, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38855673

RESUMO

In recent years, significant progress has been made in the field of medical image segmentation through the application of deep learning and neural networks. Numerous studies have focused on optimizing encoders to extract more comprehensive key information. However, the importance of decoders in directly influencing the final output of images cannot be overstated. The ability of decoders to effectively leverage diverse information and further refine crucial details is of paramount importance. This paper proposes a medical image segmentation architecture named STCS-Net. The designed decoder in STCS-Net facilitates multi-scale filtering and correction of information from the encoder, thereby enhancing the accuracy of extracting vital features. Additionally, an information enhancement module is introduced in skip connections to highlight essential features and improve the inter-layer information interaction capabilities. Comprehensive evaluations on the ISIC2016, ISIC2018, and Lung datasets validate the superiority of STCS-Net across different scenarios. Experimental results demonstrate the outstanding performance of STCS-Net on all three datasets. Comparative experiments highlight the advantages of our proposed network in terms of accuracy and parameter efficiency. Ablation studies confirm the effectiveness of the introduced decoder and skip connection module. This research introduces a novel approach to the field of medical image segmentation, providing new perspectives and solutions for future developments in medical image processing and analysis.

2.
J Am Chem Soc ; 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38847772

RESUMO

Despite the synthetic versatility of difluorocarbene, its high reactivity severely regulates widespread applications of difluorocarbene in organic synthesis. Here, we report a copper difluorocarbene-involved catalytic coupling, representing a new mode of the difluoromethylation reaction. This method allows difluoromethylation of a wide range of readily available allyl/propargyl electrophiles with NaBH3CN and low-cost difluorocarbene precursor BrCF2CO2K, featuring high cost-efficiency, high stereo- and regioselectivities, and high functional group tolerance, even with complex drug-like molecules. Applying the method led to the efficient synthesis of deuterated difluoromethylated compounds of medicinal interest. The resulting difluoromethylated allyl and allenyl products can serve as versatile synthons for diverse transformations, rendering the approach attractive for synthesizing complex fluorinated structures. Experimental mechanistic studies and computational calculations reveal that the formation of a difluoromethylcopper(I) intermediate through the nucleophilic attack of boron hydride on the copper(I) difluorocarbene is the key step in the reaction.

3.
Environ Pollut ; 352: 124103, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38734053

RESUMO

At present, the quantity of micro/nano plastics in the environment is steadily rising, and their pollution has emerged as a global environmental issue. The tendency of their bioaccumulation in aquatic organisms (especially fish) has intensified people's attention to their persistent ecotoxicology. This review critically studies the accumulation of fish in the intestines of fish through active or passive intake of micro/nano plastics, resulting in their accumulation in intestinal organs and subsequent disturbance of intestinal microflora. The key lies in the complex toxic effect on the host after the disturbance of fish intestinal microflora. In addition, this review pointed out the characteristics of micro/nano plastics and the effects of their combined toxicity with adsorbed pollutants on fish intestinal microorganisms, in order to fully understand the characteristics of micro/nano plastics and emphasize the complex interaction between MNPs and other pollutants. We have an in-depth understanding of MNPs-induced intestinal flora disorders and intestinal dysfunction, affecting the host's systemic system, including immune system, nervous system, and reproductive system. The review also underscores the imperative for future research to investigate the toxic effects of prolonged exposure to MNPs, which are crucial for evaluating the ecological risks posed by MNPs and devising strategies to safeguard aquatic organisms.


Assuntos
Disbiose , Peixes , Microbioma Gastrointestinal , Poluentes Químicos da Água , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Disbiose/induzido quimicamente , Peixes/microbiologia , Poluentes Químicos da Água/toxicidade , Microplásticos/toxicidade , Plásticos , Doenças dos Peixes/microbiologia , Doenças dos Peixes/induzido quimicamente , Nanopartículas/toxicidade
4.
Transl Oncol ; 46: 101989, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38781861

RESUMO

Lung cancer has one of the highest mortality rates worldwide, with non-small-cell lung cancer (NSCLC) constituting approximately 85% of all cases. Demethylzeylasteral (DEM), extracted from Tripterygium wilfordii Hook F, exhibits notable anti-tumor properties. In this study, we revealed that DEM could effectively induce NSCLC cell apoptosis. Specifically, DEM can dose-dependently suppress the viability and migration of human NSCLC cells. RNA-seq analysis revealed that DEM regulates the P53-signaling pathway, which was further validated by assessing crucial proteins involved in this pathway. Biacore analysis indicated that DEM has high affinity with the P53 protein. The CDX model demonstrated DEM's anti-tumor actions. This work provided evidence that DEM-P53 interaction stabilizes P53 protein and triggers downstream anti-tumor activities. These findings indicate that DEM treatment holds promise as a potential therapeutic approach for NSCLC, which warrants further clinical assessment in patients with NSCLC.

5.
Chin J Nat Med ; 22(4): 318-328, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38658095

RESUMO

Double cortin-like kinase 1 (DCLK1) exhibits high expression levels across various cancers, notably in human colorectal cancer (CRC). Diacerein, a clinically approved interleukin (IL)-1ß inhibitor for osteoarthritis treatment, was evaluated for its impact on CRC proliferation and migration, alongside its underlying mechanisms, through both in vitro and in vivo analyses. The study employed MTT assay, colony formation, wound healing, transwell assays, flow cytometry, and Hoechst 33342 staining to assess cell proliferation, migration, and apoptosis. Additionally, proteome microarray assay and western blotting analyses were conducted to elucidate diacerein's specific mechanism of action. Our findings indicate that diacerein significantly inhibits DCLK1-dependent CRC growth in vitro and in vivo. Through high-throughput proteomics microarray and molecular docking studies, we identified that diacerein directly interacts with DCLK1. Mechanistically, the suppression of p-STAT3 expression following DCLK1 inhibition by diacerein or specific DCLK1 siRNA was observed. Furthermore, diacerein effectively disrupted the DCLK1/STAT3 signaling pathway and its downstream targets, including MCL-1, VEGF, and survivin, thereby inhibiting CRC progression in a mouse model, thereby inhibiting CRC progression in a mouse model.


Assuntos
Antraquinonas , Proliferação de Células , Neoplasias Colorretais , Quinases Semelhantes a Duplacortina , Peptídeos e Proteínas de Sinalização Intracelular , Proteínas Serina-Treonina Quinases , Fator de Transcrição STAT3 , Transdução de Sinais , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT3/genética , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Humanos , Transdução de Sinais/efeitos dos fármacos , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Animais , Camundongos , Proliferação de Células/efeitos dos fármacos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/genética , Antraquinonas/farmacologia , Linhagem Celular Tumoral , Reposicionamento de Medicamentos , Apoptose/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Camundongos Nus
6.
Mol Plant Pathol ; 25(3): e13425, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38462784

RESUMO

Phosphatases are important regulators of protein phosphorylation and various cellular processes, and they serve as counterparts to kinases. In this study, our comprehensive analysis of oomycete complete proteomes unveiled the presence of approximately 3833 phosphatases, with most species estimated to have between 100 and 300 putative phosphatases. Further investigation of these phosphatases revealed a significant increase in protein serine/threonine phosphatases (PSP) within oomycetes. In particular, we extensively studied the metallo-dependent protein phosphatase (PPM) within the PSP family in the model oomycete Phytophthora sojae. Our results showed notable differences in the expression patterns of PPMs throughout 10 life stages of P. sojae, indicating their vital roles in various stages of oomycete pathogens. Moreover, we identified 29 PPMs in P. sojae, and eight of them possessed accessory domains in addition to phosphate domains. We investigated the biological function of one PPM protein with an extra PH domain (PPM1); this protein exhibited high expression levels in both asexual developmental and infectious stages. Our analysis confirmed that PPM1 is indeed an active protein phosphatase, and its accessory domain does not affect its phosphatase activity. To delve further into its function, we generated knockout mutants of PPM1 and validated its essential roles in mycelial growth, sporangia and oospore production, as well as infectious stages. To the best of our knowledge, this study provides the first comprehensive inventory of phosphatases in oomycetes and identifies an important phosphatase within the expanded serine/threonine phosphatase group in oomycetes.


Assuntos
Oomicetos , Phytophthora , Proteoma/metabolismo , Phytophthora/metabolismo , Fosfoproteínas Fosfatases/genética , Fosfoproteínas Fosfatases/metabolismo , Serina/metabolismo
7.
Materials (Basel) ; 17(5)2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38473461

RESUMO

A facile method for the immobilization of ß-cyclodextrin on polysulfone membranes with the aim of selectively adsorbing low-density lipoprotein (LDL) was established, which is based on the self-assembly of dopamine on the membrane followed by the Schiff base reaction with mono-(6-ethanediamine-6-deoxy)-ß-cyclodextrin. The surface modification processes were validated using X-ray photoelectron spectroscopy and attenuated total reflectance Fourier-transform infrared spectroscopy. Surface wettability and surface charge of the membranes were investigated through the water contact angle and zeta potential analysis. The cyclodextrin-modified polysulfone membrane (PSF-CD) showed good resistance to protein solutions, as shown by the measurement of BSA adsorption. The assessment of BSA adsorption revealed that the cyclodextrin-modified polysulfone membrane (PSF-CD) exhibited excellent resistance to protein solutions. To investigate the adsorption and desorption behaviors of the membranes in single-protein or binary-protein solutions, an enzyme-linked immunosorbent assay was employed. The results revealed that the PSF-CD possessed remarkable adsorption capacity and higher affinity for LDL in both single-protein and binary-protein solutions, rendering it a suitable material for LDL apheresis.

8.
Front Cell Dev Biol ; 12: 1252064, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38550378

RESUMO

N6-methyladenosine (m6A) is the most abundant chemical modification in eukaryotic cells. It is a post-transcriptional modification of mRNA, a dynamic reversible process catalyzed by methyltransferase, demethylase, and binding proteins. Ferroptosis, a unique iron-dependent cell death, is regulated by various cell metabolic events, including many disease-related signaling pathways. And different ferroptosis inducers or inhibitors have been identified that can induce or inhibit the onset of ferroptosis through various targets and mechanisms. They have potential clinical value in the treatment of diverse diseases. Until now, it has been shown that in several cancer diseases m6A can be involved in the regulation of ferroptosis, which can impact subsequent treatment. This paper focuses on the concept, function, and biological role of m6A methylation modification and the interaction between m6A and ferroptosis, to provide new therapeutic strategies for treating malignant diseases and protecting the organism by targeting m6A to regulate ferroptosis.

9.
Phytomedicine ; 128: 155538, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38552432

RESUMO

OBJECTIVE: The effect of solamargine on lung adenocarcinoma and its effect on STAT1 signaling pathway mediated immune escape were studied through network pharmacology and in vitro and in vivo experiments. METHODS: The solamargine targets were screened using the TCMSP and the LUAD targets were screened using the GeneCard, OMIM, PharmGkb, TTD and DrugBank databases. PPI network analysis and target prediction were performed using GO and KEGG. Colony formation assay, EDU staining, wound healing, transwell assay, Hoechst and flow cytometry were used to detect the effects of solamargine on the proliferation, migration and apoptosis of LUAD. Western blotting (WB) and quantitative reverse transcription polymerase chain reaction (RT-qPCR) were used to detect P-STAT1 and PD-L1 expression. And immunofluorescence was used to detect P-STAT1 expression. In vivo experiments, C57BL/6 mice were divided into control group, low concentration group, high concentration group, positive control group and combination group. Every other day, following seven consecutive doses, the size of the tumor was assessed. Finally, the expressions of P-STAT1, STAT1, PD-L1 and apoptosis index proteins were detected by WB. RESULTS: The anti-LUAD effect of solamargine was found by wound healing, colony formation assay, transwell assay, hoechst and EdU staining. The results of network pharmacological analysis showed that solamargine could suppress STAT1 expression level. Further enrichment assay of STAT1 showed that STAT1 was associated with immune-related pathways. In addition, molecular signal analysis by WB and RT-qPCR indicated that solamargine could reduce the expression levels of P-STAT1 and PD-L1 in a concentration-dependent manner. According to the results of in vivo assays, combination of solamargine and immune checkpoint inhibitors (ICIs) durvalumab could significantly inhibit the growth of Lewis transplanted tumors in C57BL/6 mice, and no toxic side effect was recoded. CONCLUSION: These results indicated that solamargine could inhibit the proliferation and promote the apoptosis of LUAD. It also could reduce the expression level of P-STAT1 protein and inhibit the expression level of PD-L1. At the same time, the combination with the ICIs can better block the expression of PD-L1 in cells, thereby inhibiting the immune escape pathway of tumor cells and achieving anti-tumor effects. This study proposed a novel combined therapeutic approach, involving the inhibition of STAT1 by solamargine in conjunction with ICIs.


Assuntos
Adenocarcinoma de Pulmão , Apoptose , Antígeno B7-H1 , Neoplasias Pulmonares , Camundongos Endogâmicos C57BL , Fator de Transcrição STAT1 , Fator de Transcrição STAT1/metabolismo , Animais , Neoplasias Pulmonares/tratamento farmacológico , Antígeno B7-H1/metabolismo , Humanos , Apoptose/efeitos dos fármacos , Adenocarcinoma de Pulmão/tratamento farmacológico , Camundongos , Proliferação de Células/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Células A549 , Inibidores de Checkpoint Imunológico/farmacologia
10.
Chem Sci ; 15(8): 2937-2945, 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38404383

RESUMO

An efficient method for the late-stage selective O-fluoroalkylation of tyrosine residues with a stable yet highly reactive fluoroalkylating reagent, 3,3-difluoroallyl sulfonium salts (DFASs), has been developed. The reaction proceeds in a mild basic aqueous buffer (pH = 11.6) with high efficiency, high biocompatibility, and excellent regio- and chemoselectivity. Various oligopeptides and phenol-containing bioactive molecules, including carbohydrates and nucleosides, could be selectively O-fluoroalkylated. The added vinyl and other functional groups from DFASs can be valuable linkers for successive modification, significantly expanding the chemical space for further bioconjugation. The synthetic utility of this protocol has been demonstrated by the fluorescently labeled anti-cancer drug and the synthesis of O-link type 1,4,7,10-tetraazacyclododecane-N,N',N,N'-tetraacetic acid-tyrosine3-octreotate (DOTA-TATE), showing the prospect of the method in medicinal chemistry and chemical biology.

11.
Eur Respir Rev ; 33(171)2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38355149

RESUMO

Lung cancer is the leading cause of cancer-related deaths worldwide, and ∼85% of lung cancers are classified as nonsmall cell lung cancer (NSCLC). These malignancies can proliferate indefinitely, in part due to dysregulation of the cell cycle and the resulting abnormal cell growth. The specific activation of cyclin-dependent kinases 4 and 6 (CDK4/6) is closely linked to tumour proliferation. Approximately 80% of human tumours exhibit abnormalities in the cyclin D-CDK4/6-INK4-RB pathway. Specifically, CDK4/6 inhibitors either as monotherapy or combination therapy have been investigated in pre-clinical and clinical studies for the treatment of NSCLC, and promising results have been achieved. This review article focuses on research regarding the use of CDK4/6 inhibitors in NSCLC, including the characteristics and mechanisms of action of approved drugs and progress of pre-clinical and clinical research.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Quinase 4 Dependente de Ciclina/metabolismo , Proliferação de Células , Inibidores de Proteínas Quinases/efeitos adversos
12.
Mikrochim Acta ; 191(3): 132, 2024 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-38351367

RESUMO

Bioaerosols are airborne suspensions of fine solid or liquid particles containing biological substances such as viruses, bacteria, cellular debris, fungal spores, mycelium, and byproducts of microbial metabolism. The global Coronavirus disease 2019 (COVID-19) pandemic and the previous emergence of severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and influenza have increased the need for reliable and effective monitoring tools for bioaerosols. Bioaerosol collection and detection have aroused considerable attention. Current bioaerosol sampling and detection techniques suffer from long response time, low sensitivity, and high costs, and these drawbacks have forced the development of novel monitoring strategies. Microfluidic technique is considered a breakthrough for high performance analysis of bioaerosols. In recent years, several emerging methods based on microfluidics have been developed and reported for collection and detection of bioaerosols. The unique advantages of microfluidic technique have enabled the integration of bioaerosol collection and detection, which has a higher efficiency over conventional methods. This review focused on the research progress of bioaerosol collection and detection methods based on microfluidic techniques, with special attention on virus aerosols and bacterial aerosols. Different from the existing reviews, this work took a unique perspective of the targets to be collected and detected in bioaerosols, which would provide a direct index of bioaerosol categories readers may be interested in. We also discussed integrated microfluidic monitoring system for bioaerosols. Additionally, the application of bioaerosol detection in biomedicine was presented. Finally, the current challenges in the field of bioaerosol monitoring are presented and an outlook given of future developments.


Assuntos
Microfluídica , Vírus , Aerossóis e Gotículas Respiratórios , Bactérias , Aerossóis/análise
13.
Int J Biol Macromol ; 259(Pt 1): 129239, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38184041

RESUMO

Loach (Misgurnus anguillicaudatus) is a common freshwater commercial fish species in China. The meat of this fish is a good source of protein and other nutrients that are needed for human health. Aquaculture challenges such as diseases and pest susceptibility, excessive density, and nutritional deficiency result in low production of loach rather than increased demand. Due to a lack of knowledge about the immune system of loaches, we carried out this study to better understand its antibacterial molecular mechanism. Here, we performed RNA sequencing from liver tissue obtained from soya bean-fermented fed loach after subjecting it to the LPS challenge. The results revealed a total of 18,399 differentially expressed genes (DEGs) in the LPS-treated and control groups. There were 7482 DEGs that were upregulated and 10,917 DEGs were downregulated. The enrichment analysis of DEGs revealed that the majority of DEGs were found to be abundant in the pathways of DNA replication, spliceosome, nucleotide exception repair, cell cycle, and Herpes simplex virus 1 infection. Furthermore, qRT-PCR analysis of 21 selected DEGs demonstrated that the transcriptomic data is extremely reliable. Overall, this study provides insight into the molecular features and control mechanisms of genes that affect loach growth. The availability of this information will also contribute to the enhancement of the breeding and protection of loach resources.


Assuntos
Cipriniformes , Transcriptoma , Animais , Humanos , Lipopolissacarídeos/farmacologia , Lipopolissacarídeos/metabolismo , Glycine max/genética , Melhoramento Vegetal , Cipriniformes/genética , Cipriniformes/metabolismo
14.
Adv Mater ; 36(16): e2212236, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36867581

RESUMO

Organic solar cells (OSCs) have made dramatic advancements during the past decades owing to the innovative material design and device structure optimization, with power conversion efficiencies surpassing 19% and 20% for single-junction and tandem devices, respectively. Interface engineering, by modifying interface properties between different layers for OSCs, has become a vital part to promote the device efficiency. It is essential to elucidate the intrinsic working mechanism of interface layers, as well as the related physical and chemical processes that manipulate device performance and long-term stability. In this article, the advances in interface engineering aimed to pursue high-performance OSCs are reviewed. The specific functions and corresponding design principles of interface layers are summarized first. Then, the anode interface layer, cathode interface layer in single-junction OSCs, and interconnecting layer of tandem devices are discussed in separate categories, and the interface engineering-related improvements on device efficiency and stability are analyzed. Finally, the challenges and prospects associated with application of interface engineering are discussed with the emphasis on large-area, high-performance, and low-cost device manufacturing.

15.
Regul Toxicol Pharmacol ; 146: 105542, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38070762

RESUMO

Arctii Fructus is the dried ripe fruit of Arctium lappa L. (family Asteraceae) and is in the Chinese pharmacopoeia. Previous research showed that the total lignans from Arctii Fructus (TLAF) have pharmacological activities related to diabetes. This study evaluated the acute and chronic (26 weeks) toxicities associated with oral daily administration of TLAF in Sprague-Dawley (SD) rats. An acute-toxicity test showed that TLAF caused 10% mortality at 3,000 mg/kg × 2 (6-h interval), with toxic symptoms, such as dyspnea and tonic convulsions, indicating potential neurotoxicity. A chronic-toxicity study showed no mortality after administration. The no observed adverse-effect level was 1,800 mg/kg (approximately 54 times higher than the human clinical dose) for 26 weeks of TLAF oral administration in SD rats, with toxicity signs of excessive oral and nasal secretions and moist circumferential hair that recovered after TLAF discontinuation. In the toxicokinetic study, the two main components of TLAF, arctigenin plasma level was positively correlated with dose and tended to accumulate after multiple doses. At 1,800 mg/kg, arctiin plasma level increased and tended to accumulate after multiple doses. These results indicated that TLFA has relatively low toxicity and the potential for clinical treatment of diabetes.


Assuntos
Diabetes Mellitus , Medicamentos de Ervas Chinesas , Lignanas , Ratos , Humanos , Animais , Ratos Sprague-Dawley , Preparações Farmacêuticas , Diabetes Mellitus/tratamento farmacológico , Lignanas/toxicidade
16.
Pharmaceutics ; 15(12)2023 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-38140070

RESUMO

Cancer is a serious disease with an abnormal proliferation of organ tissues; it is characterized by malignant infiltration and growth that affects human life. Traditional cancer therapies such as resection, radiotherapy and chemotherapy have a low cure rate and often cause irreversible damage to the body. In recent years, since the traditional treatment of cancer is still very far from perfect, researchers have begun to focus on non-invasive near-infrared (NIR)-responsive natural macromolecular hydrogel assembly drugs (NIR-NMHADs). Due to their unique biocompatibility and extremely high drug encapsulation, coupling with the spatiotemporal controllability of NIR, synergistic photothermal therapy (PTT), photothermal therapy (PDT), chemotherapy (CT) and immunotherapy (IT) has created excellent effects and good prospects for cancer treatment. In addition, some emerging bioengineering technologies can also improve the effectiveness of drug delivery systems. This review will discuss the properties of NIR light, the NIR-functional hydrogels commonly used in current research, the cancer therapy corresponding to the materials encapsulated in them and the bioengineering technology that can assist drug delivery systems. The review provides a constructive reference for the optimization of NIR-NMHAD experimental ideas and its application to human body.

17.
J Cancer ; 14(17): 3309-3320, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37928418

RESUMO

Background: Non-small-cell lung cancer (NSCLC) is the most common histological subtype of lung cancer with significant morbidity and mortality rates worldwide. Cinobufagin, the primary component of Chansu and the major active ingredient of cinobufacini, has attracted widespread attention for its excellent anticancer effects, but its activity remains poorly characterized in NSCLC. Methods: The functions of cinobufagin treatment in anti-tumor was evaluated using various in vitro and in vivo assays. The change of STAT3 signaling by cinobufagin was analyzed using molecular docking, immunofluorescence technic and western blotting. Results: In vitro, we confirmed the inhibitory effect of cinobufagin on cell viability, proliferation, migration, epithelial-mesenchymal transition (EMT), as well as an apoptosis-inducing effect. The antitumor effects of cinobufagin were confirmed in vivo by measuring tumor growth in a mouse xenograft model. Cinobufagin was found to significantly inhibit the phosphorylation of signal transducer and activator of transcription 3 (STAT3) at tyrosine 705 (Y705) in a time- and concentration-dependent manner. Moreover, cinobufagin reversed IL-6-induced nuclear translocation of STAT3. Conclusions: Our study has demonstrated that cinobufagin exerts an antitumor effect in non-small-cell lung cancer by blocking STAT3 signaling, and cinobufagin is a promising candidate agent for NSCLC therapy.

18.
Fish Shellfish Immunol ; 143: 109206, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37923184

RESUMO

Peroxinectin, which has both peroxidase and cell adhesion activities, is crucial for invertebrate innate immune responses. In this study, we first cloned the full-length cDNA of Procambarus clarkii Peroxinectin (denoted as Pc-Px) and evaluated its immune roles. The Pc-Px cDNA had 2460 base pairs (bp) and 819 amino acid residues, including peroxidase domain and a putative integrin-binding motif. Pc-Px tissue expression was found to be ubiquitous in all examined tissues under normal physiological conditions. Pc-Px mRNA levels were highest in hemocytes, followed by gills and heart, and were lowest in the gut. The LPS, PGN, and Poly I:C treatment significantly up-regulated the transcript level of Pc-Px gene, but the expression trends were different after the microbials component treatments. Pc-Px knockdown using double-stranded RNA altered the transcription profiles of various immune-related genes in hepatopancreas of P. clarkii. Taken together, Pc-Px is an important component of immune system that likely to modulate immune function of P. clarkii via regulating immune-associated genes.


Assuntos
Astacoidea , Imunidade Inata , Animais , Astacoidea/genética , Sequência de Aminoácidos , DNA Complementar/genética , Imunidade Inata/genética , Clonagem Molecular , Peroxidases , Proteínas de Artrópodes
19.
Zhen Ci Yan Jiu ; 48(11): 1175-1182, 2023 Nov 25.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-37984916

RESUMO

OBJECTIVES: To investigate the hot topics in acupuncture-moxibustion research for treatment of aphasia and explore the current situation and trend of technology transformation in this field through analyzing the relevant Chinese literatures in recent 30 years by means of knowledge graph technology. METHODS: CiteSpace 6.1.R 2 and VOSviewer V1.6.16 software were used to collate the data, draw knowledge graphs and conduct visual analysis of the literatures related to acupuncture-moxibustion treatment of aphasia, searched from CNKI, WanFang and VIP databases.The time line view and strongest bursts of keywords were formed in the field of acupuncture-moxibustion treatment for aphasia. The treatment-based keyword networks were visualized. RESULTS: A total of 773 Chinese articles were included. Through visual analysis of the co-occurrence networks, the top 10 high-frequency overall keywords and the top 10 clusters of overall keywords were listed. The top 5 high-frequency aphasia categories were Broca aphasia, hysterical aphasia, transcortical motor aphasia, nominal aphasia and sensory aphasia. Regarding the keywords of the techniques of acupuncture-moxibustion, the occurrence frequencies of scalp acupuncture, tongue acupuncture, body acupuncture and electroacupuncture were ≥ 10 times.The occurrence frequencies of 16 acupoints were ≥25 times. After collation and cluster analysis of acupoints and techniques of acupuncture-moxibustion, 7 keyword clusters of "acupuncture techniques-acupoints" were obtained. The time line view showed that the strongest burst of keywords were transcranial magnatic stimulation, language rehabilitation training, acupuncture-medicine therapy and stroke, etc. in the recent 5 years. CONCLUSIONS: Acupuncture-moxibustion displays its unique advantage in treatment of aphasia. With the deepening of modern research, the hot topics for aphasia treated with acupuncture-moxibustion are present and the achievements enriched. In future, these therapeutic methods should be further investigated to explore a model of translational medicine for aphasia in line with the characteristics of acupuncture-moxibustion.


Assuntos
Terapia por Acupuntura , Afasia , Moxibustão , Humanos , Pesquisa Translacional Biomédica , Ciência Translacional Biomédica , Reconhecimento Automatizado de Padrão , Pontos de Acupuntura , Afasia/terapia
20.
Front Endocrinol (Lausanne) ; 14: 1230168, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37670891

RESUMO

As important organelles of energetic and metabolism, changes in the dynamic state of mitochondria affect the homeostasis of cellular metabolism. Mitochondrial dynamics include mitochondrial fusion and mitochondrial fission. The former is coordinated by mitofusin-1 (Mfn1), mitofusin-2 (Mfn2), and optic atrophy 1 (Opa1), and the latter is mediated by dynamin related protein 1 (Drp1), mitochondrial fission 1 (Fis1) and mitochondrial fission factor (MFF). Mitochondrial fusion and fission are generally in dynamic balance and this balance is important to preserve the proper mitochondrial morphology, function and distribution. Diabetic conditions lead to disturbances in mitochondrial dynamics, which in return causes a series of abnormalities in metabolism, including decreased bioenergy production, excessive production of reactive oxygen species (ROS), defective mitophagy and apoptosis, which are ultimately closely linked to multiple chronic complications of diabetes. Multiple researches have shown that the incidence of diabetic complications is connected with increased mitochondrial fission, for example, there is an excessive mitochondrial fission and impaired mitochondrial fusion in diabetic cardiomyocytes, and that the development of cardiac dysfunction induced by diabetes can be attenuated by inhibiting mitochondrial fission. Therefore, targeting the restoration of mitochondrial dynamics would be a promising therapeutic target within type II diabetes (T2D) and its complications. The molecular approaches to mitochondrial dynamics, their impairment in the context of T2D and its complications, and pharmacological approaches targeting mitochondrial dynamics are discussed in this review and promise benefits for the therapy of T2D and its comorbidities.


Assuntos
Diabetes Mellitus Tipo 2 , Humanos , Dinâmica Mitocondrial , Apoptose , Homeostase , Mitocôndrias
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