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1.
J Nanobiotechnology ; 22(1): 24, 2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38191388

RESUMO

The iron oxide nanoparticles (IONPs), possessing both magnetic behavior and semiconductor property, have been extensively used in multifunctional biomedical fields due to their biocompatible, biodegradable and low toxicity, such as anticancer, antibacterial, cell labelling activities. Nevertheless, there are few IONPs in clinical use at present. Some IONPs approved for clinical use have been withdrawn due to insufficient understanding of its biomedical applications. Therefore, a systematic summary of IONPs' preparation and biomedical applications is crucial for the next step of entering clinical practice from experimental stage. This review summarized the existing research in the past decade on the biological interaction of IONPs with animal/cells models, and their clinical applications in human. This review aims to provide cutting-edge knowledge involved with IONPs' biological effects in vivo and in vitro, and improve their smarter design and application in biomedical research and clinic trials.


Assuntos
Antibacterianos , Nanopartículas Magnéticas de Óxido de Ferro , Animais , Humanos
2.
J Nanobiotechnology ; 21(1): 456, 2023 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-38017573

RESUMO

Traditional Chinese Medicines (TCMs) have been used for centuries for the treatment and management of various diseases. However, their effective delivery to targeted sites may be a major challenge due to their poor water solubility, low bioavailability, and potential toxicity. Nanocarriers, such as liposomes, polymeric nanoparticles, inorganic nanoparticles and organic/inorganic nanohybrids based on active constituents from TCMs have been extensively studied as a promising strategy to improve the delivery of active constituents from TCMs to achieve a higher therapeutic effect with fewer side effects compared to conventional formulations. This review summarizes the recent advances in nanocarrier-based delivery systems for various types of active constituents of TCMs, including terpenoids, polyphenols, alkaloids, flavonoids, and quinones, from different natural sources. This review covers the design and preparation of nanocarriers, their characterization, and in vitro/vivo evaluations. Additionally, this review highlights the challenges and opportunities in the field and suggests future directions for research. Nanocarrier-based delivery systems have shown great potential in improving the therapeutic efficacy of TCMs, and this review may serve as a comprehensive resource to researchers in this field.


Assuntos
Medicamentos de Ervas Chinesas , Nanopartículas , Medicamentos de Ervas Chinesas/farmacologia , Medicina Tradicional Chinesa , Disponibilidade Biológica , Nanotecnologia , Sistemas de Liberação de Medicamentos
3.
Zhongguo Zhong Yao Za Zhi ; 48(15): 4173-4186, 2023 Aug.
Artigo em Zh | MEDLINE | ID: mdl-37802786

RESUMO

Neuropathic pain(NP) has similar phenotypes but different sequential neuroinflammatory mechanisms in the pathological process. It is of great significance to inhibit the initiation of neuroinflammation, which has become a new direction of NP treatment and drug development in recent years. Mongolian drug Naru-3 is clinically effective in the treatment of trigeminal neuralgia, sciatica, and other NPs in a short time, but its pharmacodynamic characteristics and mechanism of analgesia are still unclear. In this study, a spinal nerve ligation(SNL) model simulating clinical peripheral nerve injury was established and the efficacy and mechanism of Naru-3 in the treatment of NPs was discussed by means of behavioral detection, side effect evaluation, network analysis, and experimental verification. Pharmacodynamic results showed that Naru-3 increased the basic pain sensitivity threshold(mechanical hyperalgesia and thermal radiation hyperalgesia) in the initiation of SNL in animals and relieved spontaneous pain, however, there was no significant effect on the basic pain sensitivity threshold and motor coordination function of normal animals under physiological and pathological conditions. Meanwhile, the results of primary screening of target tissues showed that Naru-3 inhibited the second phase of injury-induced nociceptive response of formalin test in mice and reduced the expression of inflammatory factors in the spinal cord. Network analysis discovered that Naru-3 had synergy in the treatment of NP, and its mechanism was associated with core targets such as matrix metalloproteinase-9(MMP9) and interleukin-1ß(IL-1ß). The experiment further took the dorsal root ganglion(DRG) and the stage of patho-logical spinal cord as the research objects, focusing on the core targets of inducing microglial neuroinflammation. By means of Western blot, immunofluorescence, agonists, antagonists, behavior, etc., the mechanism of Naru-3 in exerting NP analgesia may be related to the negative regulation of the MMP9/IL-1ß signaling pathway-mediated microglia p38/IL-1ß inflammatory loop in the activation phase. The relevant research enriches the biological connotation of Naru-3 in the treatment of NP and provides references for clinical rational drug use.


Assuntos
Metaloproteinase 9 da Matriz , Neuralgia , Ratos , Camundongos , Animais , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Ratos Sprague-Dawley , Doenças Neuroinflamatórias , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Medula Espinal/metabolismo , Transdução de Sinais , Hiperalgesia/tratamento farmacológico , Hiperalgesia/metabolismo , Neuralgia/tratamento farmacológico , Neuralgia/metabolismo
4.
Zhongguo Zhong Yao Za Zhi ; 48(23): 6457-6474, 2023 Dec.
Artigo em Zh | MEDLINE | ID: mdl-38212003

RESUMO

The Baimai Ointment with the effect of relaxing sinew and activating collaterals demonstrates a definite effect on Baimai disease with pain, spasm, stiffness and other symptoms, while the pharmacodynamic characteristics and mechanism of this agent remain unclear. In this study, a rat model of chronic compression of L4 dorsal root ganglion(CCD) was established by lumbar disc herniation, and the efficacy and mechanism of Baimai Ointment in the treatment of CCD were preliminarily explored by behavioral tests, side effect evaluation, network analysis, antagonist and molecular biology verification. The pharmacodynamic experiment indicated that Baimai Ointment significantly improved the pain thresholds(mechanical pain, thermal pain, and cold pain) and gait behavior of CCD model rats without causing tolerance or obvious toxic and side effects. Baimai Ointment inhibited the second-phase nociceptive response of mice in the formalin test, increased the hot plate threshold of normal mice, and down-regulated the expression of inflammatory cytokines in the spinal cord. Network analysis showed that Baimai Ointment had synergistic effect in the treatment of CCD and was related to descending inhibition/facilitation system and neuroinflammation. Furthermore, behavioral tests, Western blot, and immunofluorescence assay revealed that the pain-relieving effect of Baimai Ointment on CCD may be related to the regulation of the interaction between neuroactive ligand and receptors(neuroligands) such as CHRNA7, ADRA2A, and ADRB2, and the down-regulation of the expression of NOS2/pERK/PI3K, the core regulatory element of HIF-1 signaling pathway in spinal microglia. The findings preliminarily reveal the mechanism of relaxing sinew and activating collaterals of Baimai Ointment in the treatment of Baimai disease, providing a reference for the rational drug use and further research of this agent.


Assuntos
Dor Crônica , Medicamentos de Ervas Chinesas , Ratos , Camundongos , Animais , Dor Crônica/complicações , Dor Crônica/metabolismo , Ratos Sprague-Dawley , Gânglios Espinais/metabolismo , Ligantes , Transdução de Sinais , Hiperalgesia/tratamento farmacológico , Hiperalgesia/etiologia , Hiperalgesia/metabolismo
5.
Org Biomol Chem ; 20(43): 8415-8419, 2022 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-36278798

RESUMO

A formal [4 + 2] annulation of diamines and prop-2-ynyl sulfonium salts was developed. This strategy enables efficient access to tetrahydroquinoxalines in excellent yields.


Assuntos
Diaminas , Sais
6.
Angew Chem Int Ed Engl ; 61(42): e202209687, 2022 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-36039479

RESUMO

Soft matter catalyst system allowing controllable manipulation of the organized nanostructure and surface property holds the potential for renewable energy. Here we demonstrate the construction of a continuously regenerative hydrogel photocatalyst that confines the metal-thiolate coordination induced nanocavity into robust micro-sized spongy network for water splitting. Thanks to low vaporization enthalpy and fast proton mobility of water molecules confining in nanocavities, the composite delivers outstanding photocatalytic H2 production (TOF of 4568 H2 h-1 ), nearly 4.5 times higher than that on the catalyst without confinements. Incorporating with conductive polymers, the TOF is substantially improved to 7819 H2 h-1 . Impressively, continuous regeneration is for the first time achieved with H2 production retention improved from 24 % to 72 % by regulating optically-active catalyst surfaces. This optical regeneration method provides new avenues for sustainable solar energy conversion.

7.
Nanomedicine ; 15(1): 86-97, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30244085

RESUMO

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths worldwide. Current therapies present significant limitations. Triptolide (TP) is highly effective against multiple cancers including HCC. However, high toxicity, low water solubility, and unknown therapeutic targets limit its clinical application. Herein, we designed galactosylated-chitosan-TP-nanoparticles (GC-TP-NPs) with high drug loading capacities for targeted delivery to HCC. In addition to a sustained release pattern, an efficient asialoglycoprotein receptor mediated cellular uptake in vitro, and high liver tumor accumulation in vivo, GC-TP-NPs showed lower systemic and male reproductive toxicities than free TP. Importantly, GC-TP-NPs retained the anti-cancer activities of the free TP, exerting the same pro-apoptotic and anti-proliferative effects on HCC cells in vitro, and displayed higher efficacies in reducing tumor sizes in vivo. Further investigation revealed that GC-TP-NPs induced cancer cell apoptosis via blocking TNF/NF-κB/BCL2 signaling. Collectively, GC-TP-NP represents a promising candidate in halting liver cancer progression while minimizing systemic toxicity.


Assuntos
Carcinoma Hepatocelular/prevenção & controle , Quitosana/química , Diterpenos/administração & dosagem , Galactose/química , Neoplasias Hepáticas/prevenção & controle , Nanopartículas/administração & dosagem , Fenantrenos/administração & dosagem , Reprodução , Animais , Antineoplásicos Alquilantes/administração & dosagem , Antineoplásicos Alquilantes/química , Antineoplásicos Alquilantes/farmacocinética , Apoptose , Carcinoma Hepatocelular/patologia , Proliferação de Células , Diterpenos/química , Diterpenos/farmacocinética , Compostos de Epóxi/administração & dosagem , Compostos de Epóxi/química , Compostos de Epóxi/farmacocinética , Humanos , Neoplasias Hepáticas/patologia , Masculino , Camundongos , Camundongos Nus , Nanopartículas/química , Fenantrenos/química , Fenantrenos/farmacocinética , Transdução de Sinais , Distribuição Tecidual , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
8.
Zhongguo Zhong Yao Za Zhi ; 44(16): 3415-3422, 2019 Aug.
Artigo em Zh | MEDLINE | ID: mdl-31602903

RESUMO

Growing clinical evidence shows that a partial rheumatoid arthritis( RA) patient treated with Tripterygium Glycosides Tablets( TGT) may fail to achieve clinical improvement. It is of great clinical significance to predict the therapeutic effect of TGT in RA. Therefore,the aim of the current study was to identify potential biomarkers for TGT treatment in RA. Affymetrix EG1.0 arrays were applied to detect gene expression in peripheral blood mononuclear cells obtained from 6 RA patients( 3 responders and 3 non-responders) treated with TGT. By integrating differential expression data analysis and biomolecular network analysis,360 mRNAs( 185 up-regulated and 175 down-regulated) and 24 miRNAs( 7 up-regulated and 17 down-regulated) which were differentially expressed between TGT responder and non-responder groups were identified. A total of 206 candidate target genes for the differentially expressed miRNAs were obtained based on miRanada and Target Scan databases,and then the miRNA target gene coexpression network and miRNA-mediated gene signal transduction network were constructed. Following the network analyses,three candidate miRNAs biomarkers( hsa-miR-4720-5 p,hsa-miR-374 b-5 p,hsa-miR-185-3 p) were identified as candidate biomarkers predicting individual response to TGT. Partialleast-squares( PLS) was applied to construct a model for predicting response to TGT based on the expression levels of the candidate gene biomarkers in RA patients. The five-fold cross-validation showed that the prediction accuracy( ACC) of this PLS-based model efficacy was 100.00%,100.00%,100.00%,66.67% and 66.67% respectively,and all the area under the receiver operating characteristic curve( AUC) were 1.00,indicating the highly predictive efficiency of this PLS-based model. In conclusion,the integrating transcription data mining and biomolecular network investigation show that hsa-mir-4720-5 p,hsa-mir-374 b-5 p and hsa-mir-185-3 p may be candidate biomarkers predicting individual response to TGT. In addition,the PLS model based on the expression levels of these candidate biomarkers may be helpful for the clinical screen of RA patients,which potentially benefit individualized therapy of RA in a daily clinical setting.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Glicosídeos/uso terapêutico , MicroRNAs/genética , Tripterygium/química , Biomarcadores , Mineração de Dados , Humanos , Leucócitos Mononucleares , Comprimidos
9.
Acta Pharmacol Sin ; 39(6): 988-997, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28816231

RESUMO

Wu-tou Decoction (WTD) is a classic herbal formula in traditional Chinese medicine for the treatment of joint diseases, neuropathic pain (NP) and inflammatory pain. In this study we investigated whether WTD produced analgesic action in a mouse spinal nerve ligation (SNL) model and elucidated the underlying molecular mechanisms. Mice were subjected to SNL and orally treated with WTD (3.15, 6.30 or 12.60 g·kg-1·d-1) for 21 d. SNL induced mechanical hyperalgesia and heat hyperalgesia characterized by rapid and persistent pain hypersensitivity. In addition, the expression levels of IL-1ß, TNF-α, CCL2 and CXCL1 in the spinal cord dorsal horn were dramatically increased on the 10th d post-surgery. Oral administration of WTD dose-dependently suppressed both mechanical and heat hyperalgesia as well as the expression levels of inflammatory cytokines in the spinal cord dorsal horn on the 21st d post-surgery. Then whole-genome microarray analyses were conducted to detect the gene expression profiles of spinal cord dorsal horn in SNL mice with or without WTD treatment. After construction of the WTD-SNL-network and topological analysis, a list of candidate target genes of WTD acting on SNL-induced NP was identified and found to be functionally enriched in several glial cell activation-related pathways and neuroinflammatory pathways. Our data have clarified the gene expression patterns in the mouse spinal cord under the NP condition. We also demonstrate the analgesic action of WTD through suppression of glial cell activation and neuroinflammation, which suggest the potential of WTD as a promising candidate for the treatment of NP.


Assuntos
Analgésicos/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Perfilação da Expressão Gênica/métodos , Medicina Tradicional Chinesa/métodos , Neuralgia/tratamento farmacológico , Análise de Sequência com Séries de Oligonucleotídeos , Corno Dorsal da Medula Espinal/efeitos dos fármacos , Biologia de Sistemas/métodos , Administração Oral , Analgésicos/administração & dosagem , Animais , Comportamento Animal/efeitos dos fármacos , Citocinas/genética , Citocinas/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/administração & dosagem , Regulação da Expressão Gênica , Redes Reguladoras de Genes/efeitos dos fármacos , Masculino , Camundongos Endogâmicos ICR , Neuralgia/genética , Neuralgia/metabolismo , Neuralgia/fisiopatologia , Limiar da Dor/efeitos dos fármacos , Células do Corno Posterior/efeitos dos fármacos , Células do Corno Posterior/metabolismo , Transdução de Sinais/efeitos dos fármacos , Corno Dorsal da Medula Espinal/metabolismo , Corno Dorsal da Medula Espinal/fisiopatologia , Fatores de Tempo , Transcriptoma
10.
Acta Pharmacol Sin ; 39(6): 975-987, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28858293

RESUMO

Guanxinjing capsules (GXJCs) are used in traditional Chinese medicine as a common therapy for coronary heart disease (CHD) complicated with depression. In this study, we aimed to identify the main active constituents in GXJCs and to investigate the mechanisms of GXJC action on CHD complicated with depression. The chemical constituent profile of the GXJC was identified by UHPLC-LTQ-Orbitrap assay, and oral bioavailability was evaluated to screen the GXJC drug-like chemical constituents. A total of 16 GXJC drug-like chemical constituents were identified. Then, putative targets of the GXJC drug-like chemical constituents were predicted using MedChem Studio, with 870 genes found to be the putative targets of these molecules. After that, a GXJC putative target-known CHD/depression therapeutic target network was constructed, and four topological features, including degree, betweenness, closeness and K-coreness, were calculated. According to the topological feature values of the GXJC putative targets, 14 main active constituents were identified because their corresponding putative targets had topological importance in the GXJC putative target-known CHD/depression therapeutic target network, which were defined as the candidate targets of GXJC against CHD complicated with depression. Functionally, these candidate targets were significantly involved in several CHD/depression-related pathways, including repairing pathological vascular changes, reducing platelet aggregation and inflammation, and affecting patient depression. This study identified a list of main active constituents of GXJC acting on CHD complicated with depression using an integrative pharmacology-based approach that combined active chemical constituent identification, drug target prediction and network analysis. This method may offer an efficient way to understand the pharmacological mechanisms of traditional Chinese medicine prescriptions.


Assuntos
Doença das Coronárias/tratamento farmacológico , Depressão/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Medicina Tradicional Chinesa/métodos , Transdução de Sinais/efeitos dos fármacos , Biologia de Sistemas/métodos , Administração Oral , Disponibilidade Biológica , Cápsulas , Cromatografia Líquida de Alta Pressão , Doença das Coronárias/complicações , Doença das Coronárias/metabolismo , Doença das Coronárias/psicologia , Depressão/etiologia , Depressão/metabolismo , Depressão/psicologia , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/efeitos adversos , Medicamentos de Ervas Chinesas/farmacocinética , Humanos , Mapas de Interação de Proteínas , Espectrometria de Massas por Ionização por Electrospray , Espectrofotometria Ultravioleta , Resultado do Tratamento
11.
Mil Med Res ; 9(1): 30, 2022 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-35698214

RESUMO

BACKGROUND: Malaria is a devastating infectious disease that disproportionally threatens hundreds of millions of people in developing countries. In the history of anti-malaria campaign, chloroquine (CQ) has played an indispensable role, however, its mechanism of action (MoA) is not fully understood. METHODS: We used the principle of photo-affinity labeling and click chemistry-based functionalization in the design of a CQ probe and developed a combined deconvolution strategy of activity-based protein profiling (ABPP) and mass spectrometry-coupled cellular thermal shift assay (MS-CETSA) that identified the protein targets of CQ in an unbiased manner in this study. The interactions between CQ and these identified potential protein hits were confirmed by biophysical and enzymatic assays. RESULTS: We developed a novel clickable, photo-affinity chloroquine analog probe (CQP) which retains the antimalarial activity in the nanomole range, and identified a total of 40 proteins that specifically interacted and photo-crosslinked with CQP which was inhibited in the presence of excess CQ. Using MS-CETSA, we identified 83 candidate interacting proteins out of a total of 3375 measured parasite proteins. At the same time, we identified 8 proteins as the most potential hits which were commonly identified by both methods. CONCLUSIONS: We found that CQ could disrupt glycolysis and energy metabolism of malarial parasites through direct binding with some of the key enzymes, a new mechanism that is different from its well-known inhibitory effect of hemozoin formation. This is the first report of identifying CQ antimalarial targets by a parallel usage of labeled (ABPP) and label-free (MS-CETSA) methods.


Assuntos
Antimaláricos , Malária , Antimaláricos/farmacologia , Antimaláricos/uso terapêutico , Cloroquina/farmacologia , Cloroquina/uso terapêutico , Humanos , Malária/tratamento farmacológico , Espectrometria de Massas
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