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1.
Pestic Biochem Physiol ; 202: 105970, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38879314

RESUMO

This study aimed to develop a relatively natural and safe botanical insecticide for controlling the storage pest Tribolium castaneum in the egg and pupal stages. It examined how Elsholtzia densa Benth. essential oil (EO) and its primary components, ß-caryophyllene and limonene, affected T. castaneum eggs and pupae through contact and fumigation. Among th, the contact activities of ß-caryophyllene against T. castaneum eggs and pupae are LD50 (median lethal dose, 50%) = 0.156 mg/cm2 and ED50 (median effective dose, 50%) = 16.35 mg/pupa respectively. The study also investigated the effect of ß-caryophyllene and limonene on T. castaneum eggs and pupae through synergistic contact and fumigation. When the mixing ratio of ß-caryophyllene and limonene was 7:1, the LD50 value of contact activity against T. castaneum eggs was reduced to 0.100 mg/cm2, displaying an obvious synergistic effect. Experiments were conducted to investigate the antitoxic effect of ß-caryophyllene on T. castaneum eggs and pupae, as well as its effects on the enzymatic activity of acetylcholinesterase, succinate dehydrogenase, glutathione S-transferase and carboxylesterase in T. castaneum pupae. Finally, the molecular docking techniques were employed to confirm the aforementioned effects on enzyme function. The findings of this study might help improve storage pest control with T. castaneum and create eco-friendly insecticides using E. densa EO, ß-caryophyllene, and limonene.


Assuntos
Inseticidas , Lamiaceae , Óleos Voláteis , Pupa , Tribolium , Animais , Óleos Voláteis/farmacologia , Óleos Voláteis/química , Tribolium/efeitos dos fármacos , Lamiaceae/química , Inseticidas/farmacologia , Inseticidas/química , Pupa/efeitos dos fármacos , Óvulo/efeitos dos fármacos , Limoneno/farmacologia , Sesquiterpenos Policíclicos/farmacologia , Sesquiterpenos Policíclicos/química
2.
Curr Pharm Des ; 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38867534

RESUMO

BACKGROUND: Colorectal Cancer (CRC) is one of the top three malignancies with the highest incidence and mortality. OBJECTIVE: The study aimed to identify the effect of Traditional Chinese Medicine (TCM) on postoperative patients with stage II-III CRC and explore the core herb combination and its mechanism. METHODS: An observational cohort study was conducted on patients diagnosed with stage II-III CRC from January 2016 to January 2021. The primary outcome was disease-free survival, which was compared between the patients who received TCM or not, and the secondary outcome was the hazard ratio. The relevance principle was used to obtain the candidate herb combinations, and the core combination was evaluated through an assessment of efficacy and representativeness. Then, biological processes and signaling pathways associated with CRC were obtained by Gene Ontology function, Kyoto Encyclopedia of Gene and Genomes pathway, and Wikipathway. Furthermore, hub genes were screened by the Kaplan-Meier estimator, and molecular docking was employed to predict the binding sites of key ingredients to hub genes. The correlation analysis was employed for the correlations between the hub genes and tumor-infiltrating immune cells and hypoxiarelated genes. Ultimately, a quantitative polymerase chain reaction was performed to verify the regulation of hub genes by their major ingredients. RESULTS: A total of 707 patients were included. TCM could decrease the metastatic recurrence associated with stage II-III CRC (HR: 0.61, log-rank P < 0.05). Among those patients in the TCM group, the core combination was Baizhu → Yinchen, Chenpi, and Fuling (C combination), and its antitumor mechanism was most likely related to the regulation of BCL2L1, XIAP, and TOP1 by its key ingredients, quercetin and tangeretin. The expression of these genes was significantly correlated with both tumor-infiltrating immune cells and hypoxia- related genes. In addition, quercetin and tangeretin down-regulated the mRNA levels of BCL2L1, XIAP, and TOP1, thereby inhibiting the growth of HCT116 cells. CONCLUSION: Overall, a combination of four herbs, Baizhu → Yinchen, Chenpi, and Fuling, could reduce metastatic recurrence in postoperative patients with stage II-III CRC. The mechanism may be related to the regulation of BCL2L1, XIAP, and TOP1 by its key ingredients quercetin and tangeretin.

3.
Molecules ; 29(9)2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38731415

RESUMO

Investigations have shown that storage bugs seriously harm grains during storage. In the interim, essential oils (EOs) have been proven to be a good botanical pesticide. The anti-Lasioderma serricorne properties of Elsholtzia ciliata essential oil, which was obtained by steam distillation, were evaluated using DL-limonene, carvone, and their two optical isomer components using contact, repelling, and fumigation techniques. Simultaneously, the fumigation, contact, and repellent activities of carvone and its two optical isomers mixed with DL-limonene against L. serruricorne were evaluated. The results showed that E. ciliata, its main components (R-carvone, DL-limonene), and S-carvone exhibited both fumigations (LC50 = 14.47, 4.42, 20.9 and 3.78 mg/L) and contact (LD50 = 7.31, 4.03, 28.62 and 5.63 µg/adult) activity against L.serricorne. A binary mixture (1:1) of R-carvone and DL-limonene displayed an obvious synergistic effect. A binary mixture (1:1) of carvone and its two optical isomers exhibited an obvious synergistic effect, too. Furthermore, the repellent activity of the EO, carvone, and its two optical isomers, DL-limonene, and a combination of them varied. To stop insect damage during storage, E. ciliata and its components can be utilized as bio-insecticides.


Assuntos
Inseticidas , Lamiaceae , Óleos Voláteis , Óleos Voláteis/química , Óleos Voláteis/farmacologia , Lamiaceae/química , Animais , Inseticidas/química , Inseticidas/farmacologia , Limoneno/química , Limoneno/farmacologia , Repelentes de Insetos/química , Repelentes de Insetos/farmacologia , Monoterpenos Cicloexânicos/química , Monoterpenos Cicloexânicos/farmacologia , Sinergismo Farmacológico , Fumigação
4.
Adv Mater ; 36(2): e2307756, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37974525

RESUMO

Titanium implants are widely used ; however, implantation occasionally fails due to infections during the surgery or poor osseointegration after the surgery. To solve the problem, an intelligent functional surface on titanium implant that can sequentially eradicate bacteria biofilm at the initial period and promote osseointegration at the late period of post-surgery time is designed. Such surfaces can be excited by near infrared light (NIR), with rare earth nanoparticles to upconvert the NIR light to visible range and adsorb by Au nanoparticles, supported by titanium oxide porous film on titanium implants. Under NIR irradiation, the implant converts the energy of phonon to hot electrons and lattice vibrations, while the former flows directly to the contact substance or partially reacts with the surrounding to generate reactive oxygen species, and the latter leads to the local temperature increase. The biofilm or microbes on the implant surface can be eradicated by NIR treatment in vitro and in vivo. Additionally, the surface exhibits superior biocompatibility for cell survival, adhesion, proliferation, and osteogenic differentiation, which provides the foundation for osseointegration. In vivo implantation experiments demonstrate osseointegration is also promoted. This work thus demonstrates NIR-generated electrons can sequentially eradicate biofilms and regulate the osteogenic process, providing new solutions to fabricate efficient implant surfaces.


Assuntos
Nanopartículas Metálicas , Osseointegração , Osseointegração/fisiologia , Osteogênese , Titânio/farmacologia , Ouro/farmacologia , Antibacterianos/farmacologia , Propriedades de Superfície
5.
RSC Adv ; 13(51): 36168-36180, 2023 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-38090086

RESUMO

Bacteria are introduced into natural gas transmission pipelines through water-driven gas extraction, which can exacerbate the occurrence of pipeline corrosion. This study utilized a micro-reactor to design a simulated corrosion environment that mimics natural gas gathering and transportation pipelines. The objective was to investigate the corrosion behavior of X80 pipeline steel under the combined effects of CO2, Cl-, sulfate reducing bacteria (SRB), and iron bacteria (IOB). Additionally, it aimed to elucidate the influence mechanisms of these two microorganisms on corrosion. Under a humid environment with a total pressure of 8.5 MPa and a partial pressure of CO2 at 0.85 MPa, the corrosion rate of X80 pipeline steel was observed to follow the sequence: IOB > control (asepsis) > SRB + IOB > SRB. During the initial stages of corrosion, highly active IOB becomes the primary factor contributing to corrosion. As corrosion progresses, the concentration of dissolved oxygen in the SRB system gradually decreases while SRB activity intensifies, leading to the formation of FeS through the process of corrosion. The corrosion current density (icorr) exhibited a significant decrease, thereby intensifying localized corrosion of the corrosion products beneath the film. This resulted in a maximum pitting depth of 113.5 µm. Research on the behavior of microbial-enhanced corrosion provides significant guidance in the development and implementation of protective coatings.

6.
Cell Death Discov ; 9(1): 382, 2023 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-37852974

RESUMO

Non-small-cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancer cases. NSCLC patients often have poor prognosis demanding urgent identification of novel biomarkers and potential therapeutic targets. KCNAB2 (regulatory beta subunit2 of voltage-gated potassium channel), encoding aldosterone reductase, plays a pivotal role in regulating potassium channel activity. In this research, we tested the expression of KCNAB2 as well as its potential functions in human NSCLC. Bioinformatics analysis shows that expression of KCNAB2 mRNA is significantly downregulated in human NSCLC, correlating with poor overall survival. In addition, decreased KCNAB2 expression was detected in different NSCLC cell lines and local human NSCLC tissues. Exogenous overexpression of KCNAB2 potently suppressed growth, proliferation and motility of established human NSCLC cells and promoted NSCLC cells apoptosis. In contrast, CRISPR/Cas9-induced KCNAB2 knockout further promoted the malignant biological behaviors of NSCLC cells. Protein chip analysis in the KCNAB2-overexpressed NSCLC cells revealed that KCNAB2 plays a possible role in AKT-mTOR cascade activation. Indeed, AKT-mTOR signaling activation was potently inhibited following KCNAB2 overexpression in NSCLC cells. It was however augmented by KCNAB2 knockout. In vivo, the growth of subcutaneous KCNAB2-overexpressed A549 xenografts was significantly inhibited. Collectively, KCNAB2 could be a novel effective gene for prognosis prediction of NSCLC. Targeting KCNAB2 may lead to the development of advanced therapies.

8.
Mater Today Bio ; 18: 100500, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36471893

RESUMO

Polymethyl methacrylate (PMMA) bone cement (PBC) is commonly used in orthopaedic surgery. However, polymerization volumetric shrinkage, exothermic injury, and low bioactivity prevent PBC from being an ideal material. The developed expandable P(MMA-AA-St) well overcomes the volumetric shrinkage of PBC. However, its biomechanical properties are unsatisfactory. Herein, graphene oxide (GO), a hydrophilic material with favourable biomechanics and osteogenic capability, was added to P(MMA-AA-St) to optimize its biomechanics and bioactivity. The GO-modified self-expandable P(MMA-AA-St)-GO nanocomposite (PGBCs) exhibited outstanding compressive strength (>70 â€‹MPa), water absorption, and volume expansion, as well as a longer handling time and a reduced setting temperature. The cytocompatibility of PGBCs was superior to that of PBC, as demonstrated by CCK-8 assay, live-dead cell staining, and flow cytometry. In addition, better osteoblast attachment was observed, which could be attributed to the effects of GO. The improved level of osteogenic gene and protein expression further illustrated the improved cell-material interactions between osteoblasts and PGBCs. The results of an in vivo study performed by filling bone defects in the femoral condyles of rabbits with PGBCs demonstrated promising intraoperative handling properties and convenient implantation. Blood testing and histological staining demonstrated satisfactory in vivo biosafety. Furthermore, bone morphological and microarchitecture analyses using bone tissue staining and micro-CT scanning revealed better bone-PGBCs contact and osteogenic capability. The results of this study indicate that GO modification improved the physiochemical properties, cytocompatibility, and osteogenic capability of P(MMA-AA-St) and overcame the drawbacks of PBC, allowing its material derivatives to serve as effective implantable biomaterials.

9.
RSC Adv ; 12(54): 35452-35460, 2022 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-36540246

RESUMO

A novel catalyst, consisting of hollow silica-coated porous carbon with embedded iron oxide particles (FeO x @C/SiO2), was synthesized by the extended Stöber method. Iron ions were incorporated in a resorcinol-formaldehyde resin in the presence of citric acid to form a template, which was then coated with a silica layer. The iron oxide-embedded porous carbon and hollow silica were simultaneously formed during calcination under N2 atmosphere. Through this process, silica endowed the iron oxide with low crystallinity and small size, resulting in a higher catalytic activity in the heterogeneous Fenton system for the decolorization of a methylene blue (MB) solution within 25 min. Moreover, the sample maintained 78.71% of its catalytic activity after three cycles.

10.
Apoptosis ; 27(9-10): 647-667, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35849264

RESUMO

Chemoresistance of cancer cells is a major problem in treating cancer. Knowledge of how cancer cells may die or resist cancer drugs is critical to providing certain strategies to overcome tumour resistance to treatment. Paclitaxel is known as a chemotherapy drug that can suppress the proliferation of cancer cells by inducing cell cycle arrest and induction of mitotic catastrophe. However, today, it is well known that paclitaxel can induce multiple kinds of cell death in cancers. Besides the induction of mitotic catastrophe that occurs during mitosis, paclitaxel has been shown to induce the expression of several pro-apoptosis mediators. It also can modulate the activity of anti-apoptosis mediators. However, certain cell-killing mechanisms such as senescence and autophagy can increase resistance to paclitaxel. This review focuses on the mechanisms of cell death, including apoptosis, mitotic catastrophe, senescence, autophagic cell death, pyroptosis, etc., following paclitaxel treatment. In addition, mechanisms of resistance to cell death due to exposure to paclitaxel and the use of combinations to overcome drug resistance will be discussed.


Assuntos
Antineoplásicos , Neoplasias , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose , Linhagem Celular Tumoral , Humanos , Mitose , Neoplasias/tratamento farmacológico , Neoplasias/genética , Neoplasias/patologia , Paclitaxel/farmacologia
11.
J Leukoc Biol ; 110(3): 591-604, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34231923

RESUMO

As the most successful therapy for missing teeth, dental implant has become increasingly prevalent around the world. A lot of papers have reported diverse local risk factors affecting the success and survival rate of dental implants, either for a short or a long period. However, there are also many types of systemic disorders or relatively administrated medicine that may jeopardize the security and success of dental implant treatment. Additionally, the coronavirus disease 2019 pandemic also poses a challenge to dental implant clinicians. Some of these risk factors are clinically common but to some extent unfamiliar to dentists, thus optimal measurements are often lacking when they occur in dental clinics. In this review, we analyze potential systemic risk factors that may affect the success rate of dental implants. Some of them may affect bone mineral density or enhance the likelihood of local infection, thus impeding osseointegration. Others may even systemically increase the risk of the surgery and threaten patients' life. In order to help novices receive high-risk patients who need to get dental implant treatment in a more reasonable way, we accordingly review recent research results and clinical experiments to discuss promising precautions, such as stopping drugs that impact bone mineral density or the operation, and addressing any perturbations on vital signs.


Assuntos
Densidade Óssea , Implantes Dentários/normas , Falha de Restauração Dentária/estatística & dados numéricos , Osseointegração , Humanos , Fatores de Risco
12.
Cancer Cell Int ; 21(1): 221, 2021 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-33865381

RESUMO

MicroRNAs (miRNAs) are a class of small noncoding RNA molecules containing only 20-22 nucleotides. MiRNAs play a role in gene silencing and translation suppression by targeting and binding to mRNA. Proper control of miRNA expression is very important for maintaining a normal physiological environment because miRNAs can affect most cellular pathways, including cell cycle checkpoint, cell proliferation, and apoptosis pathways, and have a wide range of target genes. With these properties, miRNAs can modulate multiple signalling pathways involved in cancer development, such as cell proliferation, apoptosis, and migration pathways. MiRNAs that activate or inhibit the molecular pathway related to tumour angiogenesis are common topics of research. Angiogenesis promotes tumorigenesis and metastasis by providing oxygen and diffusible nutrients and releasing proangiogenic factors and is one of the hallmarks of tumour progression. CRC is one of the most common tumours, and metastasis has always been a difficult issue in its treatment. Although comprehensive treatments, such as surgery, radiotherapy, chemotherapy, and targeted therapy, have prolonged the survival of CRC patients, the overall response is not optimistic. Therefore, there is an urgent need to find new therapeutic targets to improve CRC treatment. In a series of recent reports, miRNAs have been shown to bidirectionally regulate angiogenesis in colorectal cancer. Many miRNAs can directly act on VEGF or inhibit angiogenesis through other pathways (HIF-1a, PI3K/AKT, etc.), while some miRNAs, specifically many exosomal miRNAs, are capable of promoting CRC angiogenesis. Understanding the mechanism of action of miRNAs in angiogenesis is of great significance for finding new targets for the treatment of tumour angiogenesis. Deciphering the exact role of specific miRNAs in angiogenesis is a challenge due to the high complexity of their actions. Here, we describe the latest advances in the understanding of miRNAs and their corresponding targets that play a role in CRC angiogenesis and discuss possible miRNA-based therapeutic strategies.

13.
ACS Appl Mater Interfaces ; 12(46): 51885-51903, 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33166458

RESUMO

Bone defect repair at load-bearing sites is a challenging clinical problem for orthopedists. Defect reconstruction with implants is the most common treatment; however, it requires the implant to have good mechanical properties and the capacity to promote bone formation. In recent years, the piezoelectric effect, in which electrical activity can be generated due to mechanical deformation, of native bone, which promotes bone formation, has been increasingly valued. Therefore, implants with piezoelectric effects have also attracted great attention from orthopedists. In this study, we developed a bioactive composite scaffold consisting of BaTiO3, a piezoelectric ceramic material, coated on porous Ti6Al4V. This composite scaffold showed not only appropriate mechanical properties, sufficient bone and blood vessel ingrowth space, and a suitable material surface topography but also a reconstructed electromagnetic microenvironment. The osteoconductive and osteoinductive properties of the scaffold were reflected by the proliferation, migration, and osteogenic differentiation of mesenchymal stem cells. The ability of the scaffold to support vascularization was reflected by the proliferation and migration of human umbilical vein endothelial cells and their secretion of VEGF and PDGF-BB. A well-established sheep spinal fusion model was used to evaluate bony fusion in vivo. Sheep underwent implantation with different scaffolds, and X-ray, micro-computed tomography, van Gieson staining, and elemental energy-dispersive spectroscopy were used to analyze bone formation. Isolated cervical angiography and visualization analysis were used to assess angiogenesis at 4 and 8 months after transplantation. The results of cellular and animal studies showed that the piezoelectric effect could significantly reinforce osteogenesis and angiogenesis. Furthermore, we also discuss the molecular mechanism by which the piezoelectric effect promotes osteogenic differentiation and vascularization. In summary, Ti6Al4V scaffold coated with BaTiO3 is a promising composite biomaterial for repairing bone defects, especially at load-bearing sites, that may have great clinical translation potential.


Assuntos
Compostos de Bário/química , Materiais Biocompatíveis/farmacologia , Diferenciação Celular/efeitos dos fármacos , Nanopartículas Metálicas/química , Osteogênese/efeitos dos fármacos , Titânio/química , Ligas , Animais , Materiais Biocompatíveis/administração & dosagem , Materiais Biocompatíveis/química , Pinos Ortopédicos , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/fisiologia , Proliferação de Células/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana , Humanos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Neovascularização Fisiológica/efeitos dos fármacos , Porosidade , Impressão Tridimensional , Ratos , Ratos Sprague-Dawley , Ovinos , Fator A de Crescimento do Endotélio Vascular/metabolismo
14.
Front Pharmacol ; 11: 705, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32499699

RESUMO

Various malignant tumors, including colorectal cancer, have the ability to form functional blood vessels for tumor growth and metastasis. Vasculogenic mimicry (VM) refers to the ability of highly invasive tumor cells to link each other to form vessels, which is associated with poor cancer prognosis. However, the antitumor VM agents are still lacking in the clinic. Astragalus Atractylodes mixture (AAM), a traditional Chinese medicine, has shown to inhibit VM formation; however the exact mechanism is not completely clarified. In this study, we found that HCT-116 and LoVo could form a VM network. Additionally, hypoxia increases the intracellular reactive oxygen species (ROS) level and accelerates migration, VM formation in colorectal cancer cells, while N-Acetylcysteine (NAC) could reverse these phenomena. Notably, further mechanical exploration confirmed that the matrix metalloprotease 2 (MMP2) induction is ROS dependent under hypoxic condition. On the basis, we found that AAM could effectively inhibit hypoxia-induced ROS generation, migration, VM formation as well as HIF-1α and MMP2 expression. In vivo, AAM significantly inhibits metastasis of colorectal cancer in murine lung-metastasis model. Taken together, these results verified that AAM effectively inhibits migration and VM formation by suppressing ROS/HIF-1α/MMP2 pathway in colorectal cancer under hypoxic condition, suggesting AAM could serve as a therapeutic agent to inhibit VM formation in human colorectal cancer.

15.
Front Oncol ; 9: 309, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31114754

RESUMO

Background: CD44 is widely used as a putative cancer stem cells (CSCs) marker for colorectal cancer (CRC). However, the prognostic role of CD44 in CRC remains controversial. Methods: We performed a systematic review and meta-analysis to evaluate the association of various CD44 isoforms and overall survival (OS) and clinicopathological features of CRC patients. Results: A total of 48 studies were included in the meta-analysis. Total CD44 isoforms overexpression was significantly correlated with worse OS of patients with CRC (HR = 1.32, 95% CI = 1.08-1.61, P = 0.007). In a stratified analysis, a higher level of either CD44v6 or CD44v2 had an unfavorable impact on OS (HRCD44v6 = 1.50, 95% CI = 1.10-2.14, P = 0.010; HRCD44v2 = 2.93, 95% CI = 1.49-5.77, P = 0.002). Additionally, CD44 was shown to be associated with some clinicopathological features, such as lymph node metastasis (ORCD44 = 1.56, 95% CI = 1.01-2.41, P = 0.044; ORCD44v6 = 1.97, 95% CI = 1.19-3.26, P = 0.008; ORTotal CD44 isoforms = 1.57, 95% CI = 1.15-2.14, P = 0.004), distant metastasis (ORCD44 = 2.90, 95% CI = 1.08-7.83, P = 0.035; ORTotal CD44 isoforms = 1.89, 95% CI = 1.02-3.53, P = 0.044). Moreover, a high level of CD44 showed a possible correlation with poor differentiation (ORTotal CD44 isoforms = 1.44, 95% CI = 1.00-2.08, P = 0.051), elevated level of CD44v6 tend to be correlated with tumor size (OR = 1.71, 95% CI = 0.99-2.96, P = 0.056). Conclusions: This meta-analysis demonstrated that CD44 overexpression might be an unfavorable prognostic factor for CRC patients and could be used to predict poor differentiation, lymph node metastasis and distant metastasis.

16.
J Cell Physiol ; 234(8): 13969-13976, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30618207

RESUMO

Receptor activity-modifying protein 1 (RAMP1) might be a critical regulator during bone wound healing. However, the roles and mechanisms of RAMP1 in osteogenesis remain unclear. Here, we aimed to elucidate the role of RAMP1 and explore the effects of Yes-associated protein 1 (Yap1), an effector of the Hippo/Yap pathway, in this process. We used a RAMP1 overexpression lentiviral system in bone marrow mesenchymal stem cells (BMSCs), which enhanced RAMP1 expression in an effective, appropriate, and sustained manner. Alkaline phosphatase (ALP) activity assays and alizarin red staining showed that RAMP1 promoted osteogenic differentiation of BMSCs after calcitonin gene-related peptide (CGRP) treatment (10 -8 mol/L). Moreover, real-time polymerase chain reaction and Western blot analysis indicated that RAMP1 upregulated the expression of osteogenic phenotypic markers (ALP, runt-related transcription factor 2, osteopontin; p < 0.05). To further uncover the mechanism of RAMP1 in osteogenic differentiation, we used verteporfin (10 -7 mol/L) to block Yap1. Notably, verteporfin impaired RAMP1-induced osteogenesis. Taken together, our findings confirmed that RAMP1 is a key mediator of bone regeneration and indicate that RAMP1 promotes CGRP-induced osteogenic differentiation of BMSCs via regulation of the Hippo/Yap pathway.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas de Ciclo Celular/metabolismo , Células-Tronco Mesenquimais/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Proteína 1 Modificadora da Atividade de Receptores/metabolismo , Transdução de Sinais , Animais , Calcificação Fisiológica/genética , Diferenciação Celular , Proliferação de Células , Regulação da Expressão Gênica , Vetores Genéticos/metabolismo , Via de Sinalização Hippo , Lentivirus/metabolismo , Camundongos Endogâmicos C57BL , Osteogênese/genética , Fenótipo , Proteínas de Sinalização YAP
17.
Int Immunopharmacol ; 47: 20-27, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28351780

RESUMO

AIMS: The present study is to investigate the effect of cordycepin on the expression of heme oxygenase-1 (HO-1) in lipopolysaccharide (LPS)-activated microphages, as well as its mechanism of action. METHODS: Mouse RAW264.7 cells were treated with different concentrations of cordycepin for 0-16h. Western blotting was used to determine the expression of HO-1 and the phosphorylation of c-Src and the p47phox subunit of NADPH oxidase. Intracellular reactive oxygen species (ROS) level was determined using H2DCFDA as fluorescent probe. Laser-scanning confocal microscopy was used to visualize the nuclear translocation of NF-E2-related factor 2 (Nrf2). Enzyme-linked immunosorbent assay was performed to measure the inhibitory effect of cordycepin on LPS-induced secretion of tumor necrosis factor-α and interleukin-6. RESULTS: Cordycepin induced the phosphorylation of c-Src and p47phox subunit of NADPH oxidase in RAW264.7 cells. Cordycepin increased the secretion of ROS by activating NADPH oxidase. In addition, cordycepin enhanced the expression of HO-1 in RAW264.7 cells in both dose- and time-dependent manners. Of note, elevated HO-1 expression induced by cordycepin treatment was regulated by c-Src/NADPH oxidase/ROS pathway. HO-1 expression induced by cordycepin was dependent on the activation of Nrf2, which was regulated by c-Src/NADPH oxidase/ROS. Cordycepin reduced LPS-induced secretion of proinflammatory cytokines through up-regulation of HO-1. CONCLUSION: The present study demonstrates that cordycepin induces the expression of HO-1 in RAW264.7 cells via c-Src/NADPH oxidase/ROS/Nrf2 pathway, and plays an anti-inflammatory role by inhibiting the secretion of cytokines from macrophages.


Assuntos
Anti-Inflamatórios/farmacologia , Desoxiadenosinas/farmacologia , Heme Oxigenase-1/metabolismo , Macrófagos/imunologia , Animais , Proteína Tirosina Quinase CSK , Citocinas/metabolismo , Heme Oxigenase-1/genética , Lipopolissacarídeos/imunologia , Macrófagos/efeitos dos fármacos , Camundongos , NADP/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Células RAW 264.7 , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Regulação para Cima , Quinases da Família src/metabolismo
18.
J Craniofac Surg ; 26(8): e795-8, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26595011

RESUMO

It is well known that corpus callosotomy (CC) can bring a favorable seizure control outcome for disabling generalized seizures, but the complete remission rate achieved by CC is rarely reported, and the postoperative relapse pattern is still not clear. In this study, the authors reviewed patients with medically refractory epilepsy who were suffering disabling seizures, including drop attacks, generalized tonic-clonic seizures (GTCS), tonic seizures, atonic seizures, atypical absences, and complex partial seizures. The patients underwent anterior two third or complete CC in our hospital. Seizure control outcome was evaluated postoperatively at 2 weeks, 1 month, 3 months, 6 months, thereafter, at yearly intervals. Seizure-free or >90% reduction was considered to be satisfactory. There were 14 patients with mean age 11.00 ±â€Š6.34 at surgery. Of all the patients, 6 patients underwent anterior two third CC, and the other 8 patients underwent complete CC. All the patients were postoperatively followed up for at least 1 year. Four patients (28.57%) were free of all seizure types in the first year after surgery. Among the 9 patients with follow-up longer than 3 years, 2 patients (22.22%) were free of all seizure types. In the first 3 months after surgery, more than half of the seizure free patients (55.56%) relapsed with the same seizure types as preoperatively. Although after that, there was only 1 patient relapsed. Of all the seizure types, CC achieved the most favorable seizure outcome in drop attacks. In conclusion, CC could achieve complete seizure remission in a small portion of selected candidates. Exploration of the relapse mechanism will contribute to improve the seizure outcome following CC.


Assuntos
Corpo Caloso/cirurgia , Epilepsia Resistente a Medicamentos/cirurgia , Complicações Pós-Operatórias/etiologia , Adolescente , Adulto , Criança , Pré-Escolar , China , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Recidiva , Estudos Retrospectivos
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