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1.
Opt Express ; 32(4): 6391-6408, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38439343

RESUMO

In the design of metasurfaces, integrating multiple tasks into a single small unit cell and achieving regulation through various paths pose a serious challenge. In this paper, a multipath-controlled bidirectional metasurface (MCBM) is designed to achieve polarization regulation, perfect absorption and total reflection as multitasking functions. The findings demonstrate that under different excitation conditions, when co-planar polarized terahertz (THz) waves are incident normally on the metasurface, the MCBM can convert co-planar polarization to cross-polarization, co-planar polarization to circular polarization wave in reflection mode, and co-planar polarization to cross-polarization in transmission, respectively. When co-planar polarized THz waves are incident from the back side of the metasurface, the tasks of MCBM change to broadband perfect absorption, total reflection, and transmission co-planar polarization to cross-polarization conversion. Remarkably, all operating frequency bands of these tasks are very approximate. Additionally, the multitasking functions can be switched by altering the excitation conditions, and their performance can be regulated through multipath controls, such as the temperature, voltage, and polarization status. Our design provides an effective strategy for multipath-controlled multitasking integrated devices in the THz band.

2.
Inflamm Res ; 73(7): 1123-1135, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38698180

RESUMO

OBJECTIVE: Immunotherapy targeting programmed cell death 1 (PDCD1 or PD-1) and its ligands has shown remarkable promise and the regulation mechanism of PD-1 expression has received arising attention in recent years. PDCD1 exon 3 encodes the transmembrane domain and the deletion of exon 3 produces a soluble protein isoform of PD-1 (sPD-1), which can enhance immune response by competing with full-length PD-1 protein (flPD-1 or surface PD-1) on T cell surface. However, the mechanism of PDCD1 exon 3 skipping is unclear. METHODS: The online SpliceAid program and minigene expression system were used to analyze potential splicing factors involved in the splicing event of PDCD1 exon 3. The potential binding motifs of heterogeneous nuclear ribonucleoprotein K (HNRNPK) on exon 3 predicted by SpliceAid were mutated by site-directed mutagenesis technology, which were further verified by pulldown assay. Antisense oligonucleotides (ASOs) targeting the exonic splicing silencer (ESS) on PDCD1 exon 3 were synthesized and screened to suppress the skipping of exon 3. The alternative splicing of PDCD1 exon 3 was analyzed by semiquantitative reverse transcription PCR. Western blot and flow cytometry were performed to detect the surface PD-1 expression in T cells. RESULTS: HNRNPK was screened as a key splicing factor that promoted PDCD1 exon 3 skipping, causing a decrease in flPD-1 expression on T cell membrane and an increase in sPD-1 expression. Mechanically, a key ESS has been identified on exon 3 and can be bound by HNRNPK protein to promote exon 3 skipping. Blocking the interaction between ESS and HNRNPK with an ASO significantly reduced exon 3 skipping. Importantly, HNRNPK can promote exon 3 skipping of mouse Pdcd1 gene as well. CONCLUSIONS: Our study revealed a novel evolutionarily conserved regulatory mechanism of PD-1 expression. The splicing factor HNRNPK markedly promoted PDCD1 exon 3 skipping by binding to the ESS on PDCD1 exon 3, resulting in decreased expression of flPD-1 and increased expression of sPD-1 in T cells.


Assuntos
Éxons , Ribonucleoproteínas Nucleares Heterogêneas Grupo K , Receptor de Morte Celular Programada 1 , Linfócitos T , Receptor de Morte Celular Programada 1/genética , Receptor de Morte Celular Programada 1/metabolismo , Animais , Humanos , Linfócitos T/metabolismo , Linfócitos T/imunologia , Ribonucleoproteínas Nucleares Heterogêneas Grupo K/genética , Ribonucleoproteínas Nucleares Heterogêneas Grupo K/metabolismo , Processamento Alternativo , Camundongos Endogâmicos C57BL , Camundongos , Oligonucleotídeos Antissenso/genética
3.
Bioorg Med Chem Lett ; 102: 129670, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38387692

RESUMO

Histone deacetylase 6 (HDAC6) has drawn more and more attention for its potential application in Alzheimer's disease (AD) therapy. A series of tetrahydro-ß-carboline (THßC) hydroxamic acids with aryl linker were synthesized. In enzymatic assay, all compounds exhibited nanomolar IC50 values. The most promising compound 11d preferentially inhibited HDAC6 (IC50, 8.64 nM) with approximately 149-fold selectivity over HDAC1. Molecular simulation revealed that the hydroxamic acid of 11d could bind to the zinc ion by a bidentate chelating manner. In vitro, 11d induced neurite outgrowth of PC12 cells without producing toxic effects and showed obvious neuroprotective activity in a model of H2O2-induced oxidative stress.


Assuntos
Carbolinas , Inibidores de Histona Desacetilases , Peróxido de Hidrogênio , Ratos , Animais , Desacetilase 6 de Histona , Inibidores de Histona Desacetilases/farmacologia , Peróxido de Hidrogênio/farmacologia , Ácidos Hidroxâmicos/farmacologia , Crescimento Neuronal , Histona Desacetilase 1/metabolismo , Relação Estrutura-Atividade
4.
Carcinogenesis ; 44(2): 119-128, 2023 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-36879410

RESUMO

The crucial roles of enhancer RNAs (eRNAs) in the regulation of gene expression in human diseases have drawn wider and wider attention in recent years. However, the specific expression profile and function of eRNAs are still rarely discussed in oral squamous cell carcinoma (OSCC), the most common subtype of head and neck squamous cell carcinoma (HNSC). In this study, we aimed to investigate the expression and function of an uncharacterized eRNA, insulin receptor substrate 2 enhancer RNA (IRS2e), in OSCC. We found that IRS2e was overexpressed in HNSC and its overexpression was positively correlated with a poor prognosis. The downregulation of IRS2e by short hairpin RNA significantly inhibited cell growth and induced cellular apoptosis and cell-cycle arrest in OSCC cells. Furthermore, the ablation of IRS2e inhibited tumor growth in vivo. Mechanically, IRS2e is essential for the expression of insulin receptor substrate 2 (IRS2), an oncogene nearby IRS2e in chromosome 13. Altogether, our study demonstrated that IRS2e is a novel oncogenic eRNA required for oncogene IRS2 expression in OSCC.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas/patologia , Neoplasias Bucais/patologia , Proteínas Substratos do Receptor de Insulina/genética , Proteínas Substratos do Receptor de Insulina/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , RNA Interferente Pequeno , Neoplasias de Cabeça e Pescoço/genética , Regulação Neoplásica da Expressão Gênica
5.
Opt Express ; 31(18): 29280-29299, 2023 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-37710732

RESUMO

The prevalent use of multispectral detection technology makes single-band camouflage devices ineffective, and the investigation of technology for camouflage that combines multispectral bands becomes urgent. The multifunctional-hierarchical flexibility metasurfaces (MHFM) for multispectral compatible camouflage of microwave, infrared, and visible, is proposed, fabricated, and measured. MHFM is primarily composed of an infrared shielding layer (IRSL), a radar absorbing layer (RAL), and a visible color layer (VCL). Among them, IRSL can block thermal infrared detection, and RAL can efficiently absorb microwave band electromagnetic (EM) waves. The VLC can display black (below 28°C), purple (28°C∼31°C), green (31°C∼33°C), and yellow (above 33°C) at different temperatures to achieve visible camouflage. Simulation results show that MHFM can achieve absorption higher than 90% in the 2.9∼13.9 GHz microwave band. Theoretically, the emissivity of MHFM in the infrared spectral range 3∼14 µm is less than 0.34. In addition, the MHFM consists of high-temperature-resistant materials that can be used normally at temperatures up to 175°C, providing excellent high-temperature stability. The measurement results show that the camouflage performance of the MHFM is in excellent agreement with the proposed theory. This study proposes a new method for multispectral camouflage that has broad engineering applications.

6.
Bioorg Med Chem Lett ; 81: 129148, 2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-36690041

RESUMO

Novel indole-piperazine derivatives with a hydroxamic acid moiety were designed and synthesized as selective histone deacetylase 6 (HDAC6) inhibitors. In enzymatic assays, all compounds exhibited nanomolar IC50 values. N-hydroxy-4-((4-(7-methyl-1H-indole-3-carbonyl)piperazin-1-yl)methyl)benzamide, 9c, was the most potent HDAC6 inhibitor (IC50, 13.6 nM). In vitro, 9c induced neurite outgrowth of PC12 cells without producing toxic effects, better than Tubastatin A (Tub A). Additionally, 9c demonstrated blatant neuroprotective activity in PC12 cells against H2O2-induced oxidative damage. In western blot assay, 9c could increase the acetylation of α-tubulin in a dose-dependent manner.


Assuntos
Histona Desacetilases , Peróxido de Hidrogênio , Ratos , Animais , Desacetilase 6 de Histona , Piperazina , Inibidores de Histona Desacetilases/farmacologia , Indóis/farmacologia , Crescimento Neuronal , Ácidos Hidroxâmicos/farmacologia
7.
Zhongguo Zhong Yao Za Zhi ; 48(20): 5438-5449, 2023 Oct.
Artigo em Zh | MEDLINE | ID: mdl-38114137

RESUMO

Huangqi Guizhi Wuwu Decoction is a classic prescription in traditional Chinese medicine(TCM) and is known for its effects of tonifying Qi, warming the meridians, and promoting blood circulation to alleviate obstruction. It is primarily used to treat conditions characterized by Qi stagnation, Yang deficiency, and obstruction, and it exhibits pharmacological effects such as immune regulation, anti-inflammation, analgesia, protection of the cardiovascular and cerebrovascular systems, itch relief, reduction of frostbite symptoms, antioxidative stress, promotion of cell apoptosis, and kidney protection. In modern clinical practice, it is commonly used to treat acute myocardial infarction, sequelae of cerebral infarction, cervical spondylosis, frozen shoulder, lower limb arteriosclerosis, lower limb vascular disorders, peripheral neuropathy in diabetes, and lupus nephritis. Recent research has focused on the chemical components, pharmacological effects, and clinical applications of Huangqi Guizhi Wuwu Decoction. Based on the "five principles" of quality markers(Q-markers) in TCM, this study predicted and analyzed the Q-markers of Huangqi Guizhi Wuwu Decoction. It suggested that astragaloside Ⅳ, formononetin, kaempferol, quercetin, cinnamic acid, cinnamaldehyde, 6-gingerol, paeoniflorin, albiflorin, and gallic acid could serve as Q-markers for Huangqi Guizhi Wuwu Decoction. The findings of this study can provide references for quality control of Huangqi Guizhi Wuwu Decoction and the development of new Chinese medicinal formulations.


Assuntos
Medicamentos de Ervas Chinesas , Congelamento das Extremidades , Medicamentos de Ervas Chinesas/uso terapêutico , Medicina Tradicional Chinesa , Astragalus propinquus , Congelamento das Extremidades/tratamento farmacológico
8.
Zhongguo Zhong Yao Za Zhi ; 47(19): 5171-5181, 2022 Oct.
Artigo em Zh | MEDLINE | ID: mdl-36472023

RESUMO

Shenling Baizhu San is a classic prescription for replenishing Qi to invigorate the spleen and dispelling dampness to check diarrhea, which mainly treats the syndrome of spleen deficiency and heavy dampness. With the pharmacological effects of regulating immune system, improving lung function and gastrointestinal function, and resisting oxygen, tumor, and inflammation, Shenling Baizhu San is commonly used in modern clinical practice to treat chronic obstructive pulmonary disease, pulmonary fibrosis, bronchial asthma, irritable bowel syndrome, ulcerative colitis, chronic diarrhea, and diabetic, etc. This paper summarized the chemical constituents, pharmacological effects, and clinical application of Shenling Baizhu San in recent years, and predictively analyzed the quality markers of Shenling Baizhu San according to the "five principles" of Q-marker. The Q-markers of Shenling Baizhu San involved ginsenoside Rg_1, ginsenoside Re, ginsenoside Rb_1, pachymic acid, dehydrotumulosic acid, batatasin Ⅰ, batatasin Ⅲ, diosgenin, liensinine, neferine, luteolin, quercetin, glycerol trioleate, ß-sitosterol, platycodin D, glycyrrhizic acid, glycyrrhetinic acid, liquiritin, pipecolinic acid, atractylenolide Ⅰ, atractylenolide Ⅲ, and bornyl acetate, which provided references for the quality control and follow-up research of Shenling Baizhu San.


Assuntos
Colite Ulcerativa , Medicamentos de Ervas Chinesas , Ginsenosídeos , Humanos , Ginsenosídeos/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Medicamentos de Ervas Chinesas/farmacologia , Colite Ulcerativa/tratamento farmacológico , Diarreia/tratamento farmacológico
9.
Optom Vis Sci ; 98(9): 1094-1103, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34469930

RESUMO

SIGNIFICANCE: Quantifying meibomian gland morphology from meibography images is used for the diagnosis, treatment, and management of meibomian gland dysfunction in clinics. A novel and automated method is described for quantifying meibomian gland morphology from meibography images. PURPOSE: Meibomian gland morphological abnormality is a common clinical sign of meibomian gland dysfunction, yet there exist no automated methods that provide standard quantifications of morphological features for individual glands. This study introduces an automated artificial intelligence approach to segmenting individual meibomian gland regions in infrared meibography images and analyzing their morphological features. METHODS: A total of 1443 meibography images were collected and annotated. The dataset was then divided into development and evaluation sets. The development set was used to train and tune deep learning models for segmenting glands and identifying ghost glands from images, whereas the evaluation set was used to evaluate the performance of the model. The gland segmentations were further used to analyze individual gland features, including gland local contrast, length, width, and tortuosity. RESULTS: A total of 1039 meibography images (including 486 upper and 553 lower eyelids) were used for training and tuning the deep learning model, whereas the remaining 404 images (including 203 upper and 201 lower eyelids) were used for evaluations. The algorithm on average achieved 63% mean intersection over union in segmenting glands, and 84.4% sensitivity and 71.7% specificity in identifying ghost glands. Morphological features of each gland were also fed to a support vector machine for analyzing their associations with ghost glands. Analysis of model coefficients indicated that low gland local contrast was the primary indicator for ghost glands. CONCLUSIONS: The proposed approach can automatically segment individual meibomian glands in infrared meibography images, identify ghost glands, and quantitatively analyze gland morphological features.


Assuntos
Doenças Palpebrais , Disfunção da Glândula Tarsal , Algoritmos , Inteligência Artificial , Humanos , Glândulas Tarsais/diagnóstico por imagem , Manejo de Espécimes , Lágrimas
10.
Environ Res ; 187: 109488, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32470646

RESUMO

Macro-porous poly(lauryl acrylate) cryogel sheets as oil-sorbents were prepared through UV-radiation cryo-polymerizations in 1, 4-dioxane at low temperatures (-5, -2 and 0 °C) within 30 min. The influences of total monomer concentration, crosslinking monomer amount and polymerization temperature on the formation of cryogels were studied. The chemical structure and porous morphology were characterized through the techniques of Fourier transform infrared spectroscopy, thermal gravimetric analysis, contact angle measurement and scanning electron microscopy, confirming the features of high hydrophobicity, macro-porosity and good thermal stability. As well, the comparison between conventional gels prepared at room temperature and cryogels at lower temperatures was made, showing the higher rate of cryo-polymerization than conventional polymerization under the same UV-radiation condition. The swelling investigation was carried out with several organic solvents and oils. Enhanced performance of oil absorption was observed for those cryogels considering the absorption capacity and absorption rate. Variation of initiator amount and acrylate monomers could also modulate the absorption capacity. Those cryogel oil-sorbents exhibited wide adaptability, good reusability and high-temperature tolerance. Thus, this rapid and low-cost fabrication opens out a novel pathway to prepare efficient oil-sorbents used in waste water treatment.


Assuntos
Criogéis , Raios Ultravioleta , Adsorção , Microscopia Eletrônica de Varredura , Óleos , Porosidade
11.
Opt Express ; 27(12): 16550-16559, 2019 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-31252879

RESUMO

Reconfigurable design is an effective way to achieve multifunctional devices for system integration. Limited by the feeding network for multi-resonators, multimode absorbers with more than four modes are rarely reported. In this paper, a frequency-reconfigurable metamaterial absorber/reflector resonating at 3.05, 4.45 and 5.54 GHz is proposed. Based on a stereoscopic feeding network and a strategic arranged structure with loaded switching diodes, the proposed structure can realize the reconfigurable eight operating modes, including triple-band (111)/dual-band (110, 101, 011)/single-band (100, 010, 001) absorption and reflection (000) without re-optimizing and re-engineering the structure. The simulated results are confirmed by measuring a fabricated prototype. Our design provides a strategy to realize multifunction devices in microwave or even higher frequencies.

12.
RSC Adv ; 14(18): 12762-12771, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38645526

RESUMO

The use of histone deacetylase inhibitors (HDACis) is an effective approach for cancer treatment. In this work, a series of hydroxamic acid-based HDACis with a tetrahydro-ß-carboline core and aliphatic linker have been designed and synthesized. The optimal compound 13d potently inhibited HDAC1 and showed good antiproliferative activity against different tumor cell lines in vitro. Molecular docking of 13d was conducted to rationalize the high binding affinity for HDAC1. Therefore, this work provides a new structure design for HDAC inhibitors and also offers a promising treatment for solid tumors.

13.
J Ethnopharmacol ; 324: 117728, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38216101

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Shenling Baizhu San (SLBZS) is a formula of traditional Chinese medicine (TCM) that enhances the functions of the qi, spleen, and lung. According to the theory of TCM, chronic obstructive pulmonary disease (COPD) is often caused by lung qi deficiency, and SLBZS is often used in the treatment of COPD and has achieved remarkable results. However, the active components of SLBZS absorbed in serum and the underlying mechanism of SLBZS in treating COPD remain unclear and require further studies. AIM OF THE STUDY: The objective of this study is to investigate the active components of SLBZS in rat serum, as well as the crucial targets and signaling pathways involved in the therapeutic effects of SLBZS for COPD. MATERIALS AND METHODS: First, the absorption components and metabolites of SLBZS in rat serum were identified using ultra-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS). Second, potential targets of SLBZS for the treatment of COPD were acquired from publicly accessible online sources. Cytoscape (v3.7.0) software was used to construct a component-target-pathway network and a protein-protein interaction (PPI) network. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of potential targets was performed using the Metascape database. The binding status of the active components in SLBZS to the potential targets was assessed with molecular docking technology. Finally, a cell model of COPD was successfully developed for experimental validation In vitro. RESULTS: A total of 108 active components were identified, including 30 prototype components and 78 metabolites. A total of 292 potential targets for the treatment of COPD were identified, including TNF, IL-6, TLR9, RELA, and others. The KEGG pathway included inflammatory mediator regulation of TRP channels, necroptosis, and the NF-κB signaling pathway, among others. The In vitro experiments showed that SLBZS-containing serum had the ability to decrease the levels of inflammatory factors and cell death. Additionally, it was observed that SLBZS-containing serum could control the expression levels of TLR9, MyD88, TRAF6, NF-κB, and IκBα at the mRNA and protein levels. These findings suggested that SLBZS-containing serum was likely to be involved in the regulation of the TLR9/NF-κB pathway. CONCLUSIONS: The mechanism of action of SLBZS on COPD was preliminarily elucidated using UPLC-Q-TOF-MS/MS, network pharmacology, and In vitro experiments. The primary active components and potential targets of SLBZS were identified, providing a scientific foundation for further research.


Assuntos
Medicamentos de Ervas Chinesas , Doença Pulmonar Obstrutiva Crônica , Animais , Ratos , Espectrometria de Massas em Tandem , Farmacologia em Rede , NF-kappa B , Cromatografia Líquida de Alta Pressão , Simulação de Acoplamento Molecular , Receptor Toll-Like 9 , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico
14.
Front Pharmacol ; 15: 1328632, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38375037

RESUMO

Background: The Jiawei Kongsheng Zhenzhong pill (JKZP), a Chinese herbal prescription comprised of eight Chinese crude drugs, has been historically employed to treat neurological and psychological disorders. Nevertheless, the ambiguous material basis severely hindered its progress and application. Purpose: The current study aimed to establish a rapid analytical method for identifying the chemical components of the JKZP aqueous extract and the components absorbed into the rat serum to investigate the quality markers (Q-markers) responsible for the neuroprotective effects of JKZP. Methods: The qualitative detection of the chemical components, prototype components, and metabolites of the aqueous extracts of JKZP, as well as the serum samples of rats that were administered the drug, was performed using the ultra-performance liquid chromatography- quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS) technology. This analysis combined information from literature reports and database comparisons. Moreover, the study was conducted to anticipate the potential Q-markers for the neuroprotective effects of JKZP based on the "five principles" of Q-marker determination. Results: A total of 67 compounds and 111 serum components (comprising 33 prototypes and 78 metabolites) were detected and identified. Combining the principles of quality transmission and traceability, compound compatibility environment, component specificity, effectiveness, and measurability, the study predicted that five key compounds, namely, senkyunolide H, danshensu, echinacoside, loganin, and 3,6'-disinapoyl sucrose, may serve as potential pharmacological bases for the neuroprotective effects of JKZP. Conclusion: To summarize, the UPLC-Q-TOF-MS/MS technique can be employed to rapidly and accurately identify compounds in JKZP. Five active compounds have been predicted to be the Q-markers for the neuroprotective effects of JKZP. This discovery serves as a reference for improving quality, advancing further research and development, and utilizing Chinese herbal prescriptions.

15.
Thorac Cancer ; 14(10): 881-892, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36811283

RESUMO

BACKGROUND: An increasing number of circular RNAs (circRNAs) have been shown to play an important role in the tumorigenesis of breast cancer. The aim of this study was to investigate the expression and function of circ_0001667 and its potential molecular mechanisms in breast cancer. METHODS: The expression levels of circ_0001667, miR-6838-5p and CXC chemokine ligand 10 (CXCL10) in breast cancer tissues and cells were detected by quantitative real-time PCR. Cell counting kit-8 assay, EdU assay, flow cytometry, colony formation and tube formation assays were used to detect cell proliferation and angiogenesis. The binding relationship between miR-6838-5p and circ_0001667 or CXCL10 was predicted using the starBase3.0 database and verified by dual-luciferase reporter gene assay, RIP and RNA pulldown. Animal experiments were performed to assess the function of circ_0001667 knockdown on breast cancer tumor growth. RESULTS: Circ_0001667 was highly expressed in breast cancer tissues and cells, and its knockdown inhibited proliferation and angiogenesis of breast cancer cells. Circ_0001667 sponged miR-6838-5p, and inhibition of miR-6838-5p reversed the inhibitory effect of silencing circ_0001667 on proliferation and angiogenesis of breast cancer cells. MiR-6838-5p targeted CXCL10, and overexpression of CXCL10 reverses the effect of miR-6838-5p overexpression on breast cancer cell proliferation and angiogenesis. In addition, circ_0001667 interference also reduced breast cancer tumor growth in vivo. CONCLUSION: Circ_0001667 is involved in breast cancer cell proliferation and angiogenesis through regulation of the miR-6838-5p/CXCL10 axis.


Assuntos
Quimiocinas CXC , MicroRNAs , Humanos , Animais , Ligantes , Carcinogênese , Proliferação de Células , MicroRNAs/genética , Quimiocina CXCL10/genética
16.
Mini Rev Med Chem ; 23(10): 1118-1136, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36635929

RESUMO

The application of privileged structures in drug design is an effective strategy, which usually leads to innovative hits/leads and successful structural optimization. Pyrrolo[2, 3- d]pyrimidine are such a scaffold which are frequently used in many clinical drugs. The biocompounds bearing pyrrolo[2, 3-d]pyrimidine skeleton show different pharmacological effects such as anti-neurodegenerative, anti-inflammatory, antibacterial, and antitumor activities. In this article, we reviewed the representative structures and biological characteristics of reported synthetic pyrrolo[2, 3-d]pyrimidine compounds from 2017 to 2021. The linked diseases and targets were also mentioned briefly. This work might provide a reference for the subsequent drug discovery based on pyrrolo[2, 3-d]pyrimidine scaffold.


Assuntos
Antineoplásicos , Química Farmacêutica , Pirimidinas/farmacologia , Pirimidinas/química , Descoberta de Drogas , Desenho de Fármacos , Anti-Inflamatórios/farmacologia , Relação Estrutura-Atividade , Antineoplásicos/farmacologia , Antineoplásicos/química , Pirróis/farmacologia , Pirróis/química
17.
Front Neurosci ; 17: 1223451, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37694120

RESUMO

Depression has become one of the most common public health issues around the world, and the incidence has been increasing in recent years. A large amount of clinical investigations have proven that the treatment of depression is difficult. The prognosis is poor, and the fatality rate is high. At present, western medicine is the preferred treatment for depression, but it often causes adverse clinical reactions such as dry mouth, blurred vision, and memory loss, etc. The herbal compound Xiaoyao Powder is a traditional medicine for soothing the liver and relieving depression, strengthening the spleen, and nourishing the blood. It can reduce adverse reactions. It is effective in treating depression. In this study, we elucidate the function of Xiaoyao Powder in anti-depression from the perspective of clinical application and pharmacological mechanisms such as regulating epigenetic and chemical quality markers to provide empirical and experimental theoretical results that contribute to developing future depression therapy with Xiaoyao Powder.

18.
PLoS One ; 18(8): e0290420, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37607178

RESUMO

PURPOSE: To establish a workflow to visualize the surgical anatomy in 3D based on histological data of eyes of experimental animals for improving the planning of complex surgical procedures. METHODS: Four C57BL/6J wild-type(wt) mouse eyes, three Brown Norway rat eyes and four Chinchilla Bastard rabbit eyes were enucleated and processed for standard histology with serial sections and hematoxylin and eosin staining. Image stacks were processed to obtain a representation of the eye anatomy in 3D. In addition, virtual image stacks and 3D point clouds were generated by processing sagittal sections of eyes with stepwise 180° rotation and projection around the eye axis to construct a rotationally symmetric 3D model from one single sagittal section. RESULTS: Serial sections of whole eyes of mice, rats and rabbits showed significant artifacts interfering with a practical image stack generation and straightforward 3D reconstruction despite the application of image registration techniques. A workflow was established to obtain a 3D image of the eye based on virtual image stacks and point cloud generation by rotation of a single sagittal section of the eye around the symmetry axis. By analyzing the tissue shrinkage during histological processing true biometric reconstructions of the eyes were feasible making the resulting model usable for 3D modeling and simulation, e.g. for planning of complex surgical procedures in different species. CONCLUSION: Because serial sections of the eye with standard histological protocols yielded too many artifacts for a straightforward 3D visualization we reconstructed a pseudorealistic 3D model based on virtual image stacks and point cloud generation calculated from a single sagittal section of the eye. Such a model detailing microscopic structures of the whole eye will allow for a specific planning of surgical procedures in small animal eyes in order to prevent surgical complications in a very early stage of an experiment and it will support the design and development of complex intraocular implants. It will therefore be helpful in surgical teaching and improve laboratory animal welfare by an expected reduction of experimental animal numbers. Further processing including integration of mechanical tissue properties is needed to convert these 3D models into a practical virtual reality teaching and simulation platform for eyes of several species.


Assuntos
Lagomorpha , Vertebrados , Animais , Camundongos , Coelhos , Ratos , Camundongos Endogâmicos C57BL , Fluxo de Trabalho , Bem-Estar do Animal , Artefatos , Ratos Endogâmicos BN
19.
STAR Protoc ; 4(4): 102763, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38060442

RESUMO

Desiccant-coated heat exchangers provide a practical solution for the efficient removal of moisture from the air. Here, we present a protocol to synthesize an ultra-hygroscopic polymer to develop a LiCl loaded in curdlan hydrogel (LiCl@Cur)-coated heat exchanger for deep dehumidification. We describe steps for preparing the curdlan gel solution, hydrogel, LiCl solution, and LiCl@Cur. We then detail procedures for preparing curdlan-coated and LiCl@Cur-coated heat exchangers. The coated heat exchanger described in this protocol has a maximum dehumidification capacity of 12 g/kg. For complete details on the use and execution of this protocol, please refer to Pan et al. (2023).1.


Assuntos
Temperatura Alta , beta-Glucanas , Hidrogéis
20.
Heliyon ; 9(10): e20283, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37780753

RESUMO

Endometriosis is a common disease in the field of gynaecology, exhibiting clinical manifestations such as dysmenorrhoea, pelvic masses, and infertility, affecting 2-10% of women of reproductive age worldwide. Currently, the acceptance rate of hormonal drugs in patients is low and certain side effects exist. In this study, based on network pharmacology, it was found that the Yushenhuoxue (YSHX) formula could potentially affect endometriosis through the TNF signalling pathway. Clinical studies indicated that YSHX demonstrated the ability to reduce the vas score of dysmenorrhoea, resulting in a significant down-regulation of serum ca125 and inflammatory factors (IL-6, IL-1ß, TNF-α). In vivo studies showed that stem cell mice in the YSHX group exhibited significantly reduced lesion volumes than those in the model group. Serum levels of IL-1ß and IL-6 were significantly decreased. Moreover, the phosphorylation levels of NF-κB p65 and the expression of TNF-α protein were significantly decreased. In vitro studies have shown that YSHX inhibits the proliferation, invasion, and migration of endometriotic cells. This study partially verified that YSHX contributed to the treatment of endometriosis by regulating the TNF signalling pathway and improving the inflammatory state of endometriosis.

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