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Am J Cancer Res ; 12(10): 4502-4519, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36381328


Tumor metastasis is the major cause of cancer mortality; therefore, it is imperative to discover effective therapeutic drugs for anti-metastasis therapy. In the current study, we investigated whether ivermectin (IVM), an FDA-approved antiparasitic drug, could prevent cancer metastasis. Colorectal and breast cancer cell lines and a cancer cell-derived xenograft tumor metastasis model were used to investigate the anti-metastasis effect of IVM. Our results showed that IVM significantly inhibited the motility of cancer cells in vitro and tumor metastasis in vivo. Mechanistically, IVM suppressed the expressions of the migration-related proteins via inhibiting the activation of Wnt/ß-catenin/integrin ß1/FAK and the downstream signaling cascades. Our findings indicated that IVM was capable of suppressing tumor metastasis, which provided the rationale on exploring the potential clinical application of IVM in the prevention and treatment of cancer metastasis.

Adv Biol (Weinh) ; : e2200162, 2022 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-36026561


Treatments are lacking for sarcopenia, which is an age-related disease characterized by loss of skeletal muscle mass, strength, and/or physical performance. Icariin is a phytomolecule from herbal Epimedium, a traditional Chinese medicine widely used to treat musculoskeletal disorders for thousands of years. Here the effects of icariin against sarcopenia are investigated and the underlying mechanism is elucidated. A classic rat model of bilaterally orchiectomized (ORX) is used to induce sarcopenia. After administration for 8 weeks, compared to the control group, the forelimb grip strength, the specific tetanic forces of the soleus (SOL) and extensor digitorum longus muscle (EDL) are higher, and the fiber cross-sectional areas (CSAs) of the gastrocnemius and tibialis anterior muscle are larger in the icariin group. In addition, icariin promotes mRNA and protein expressions of myosin heavy chain (MyHC) both in SOL and EDL. Mechanistically, icariin significantly suppresses the mRNA and protein expressions of FOXO3a, atrogin-1, and MuRF-1, which are related to the degradation of myosin heavy chain. Collectively, icariin protects from sarcopenia in ORX rats characterized by enhancing grip strength and skeletal muscle contraction, as well as increasing skeletal muscle CSA by inhibiting the ubiquitination degradation of the MyHC in skeletal muscle fibers.

Artigo em Inglês | MEDLINE | ID: mdl-34601086


The insects have different physiological and morphological characteristics in various developmental stages. The difference in the characteristics may be related to the different sensitivity of insects to insecticides. In avermectin resistant strain screening assay, we found that the Drosophila larvae displayed a higher sensitivity to the insecticidal effect of avermectin, compared with adults. In this study, we found that the Drosophila larvae have relatively thicker chitin layer, faster avermectin metabolism and lower P-glycoprotein (P-gp) level, when compared with the adults. Besides, the expression levels of the molecular targets of avermectin, glutamate-gated chloride channel and γ-aminobutyric acid (GABA)-gated chloride channel, are lower in the larval stage than the adult. These results suggested that lower P-gp level in the body especially in brain may be the major reason for the higher sensitivity of Drosophila larvae to the insecticide. In summary, these results shed new light on the concept that different developmental stages of insects display different sensitivity to the same insecticide, which also provided a physiological explanation of the relevant mechanism of the difference of sensitivity of insect at its larval and adult stages to insecticide.

Drosophila melanogaster/metabolismo , Resistência a Inseticidas , Inseticidas/toxicidade , Ivermectina/análogos & derivados , Larva/metabolismo , Animais , Ivermectina/toxicidade
C R Biol ; 333(9): 637-41, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20816643


The present study aimed at determining the functional characteristics of anti-neuroexcitation peptide II (ANEPII). The depressant insect toxin ANEPII from the Chinese scorpion Buthus martensii Karsch had an effect on insect sodium channels. Previous studies showed that scorpion depressant toxins induce insect flaccid paralysis upon binding to receptor site-4, so we tried to predict the functional residues involved using computational techniques. In this study, three-dimensional structure modeling of ANEPII and site-4 of the insect sodium channel were carried out by homology modeling, and these models were used as the starting point for nanosecond-duration molecular dynamics simulations. Docking studies of ANEPII in the sodium channel homology model were conducted, and likely ANEPII binding loci were investigated. Based on these analyses, the residues Tyr34, Trp36, Gly39, Leu40, Trp53, Asn58, Gly61 and Gly62 were predicted to interact with sodium channel receptor and to act as functional residues.

Proteínas de Drosophila/metabolismo , Venenos de Escorpião/metabolismo , Escorpiões/metabolismo , Canais de Sódio/metabolismo , Sequência de Aminoácidos , Animais , Domínio Catalítico , Clonagem Molecular , Simulação por Computador , Proteínas de Drosophila/química , Biblioteca Gênica , Modelos Moleculares , Dados de Sequência Molecular , Ligação Proteica , Mapeamento de Interação de Proteínas , Proteínas Recombinantes de Fusão/metabolismo , Venenos de Escorpião/química , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Canais de Sódio/química
Biochem Biophys Res Commun ; 394(2): 330-4, 2010 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-20206129


An increasing number of analgesic peptides have been found in the tail toxicyst, but there has been little research into their analgesic domains. Where are the analgesic domains in a conservative betaalphabetabeta topology conformation of the analgesic peptides? We have carried out research to address this question. On account of the importance of disulfide bonds in the study of protein structure, the conformational stability, catalytic activity and folding, and site-directed mutagenesis in disulfide bridges have been used to look for the analgesic domain in a mature antitumor-analgesic peptide from the venom of the Chinese scorpion Buthus martensii Karsch (BmK AGAP). The mouse-twisting assay was used to examine the analgesic activity of 12 mutants, in which two mutants (C22S, C46S) and (C16S, C36S), exhibited lower relative activity. Following the conformational analysis, one domain, called the "core domain", was found to be the key to the analgesic activity.

Analgésicos/química , Venenos de Escorpião/química , Sequência de Aminoácidos , Analgésicos/farmacologia , Animais , Bioensaio , Dissulfetos/química , Camundongos , Modelos Moleculares , Dados de Sequência Molecular , Mutagênese Sítio-Dirigida , Dor/tratamento farmacológico , Estrutura Terciária de Proteína , Venenos de Escorpião/genética , Venenos de Escorpião/farmacologia