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1.
Am J Pathol ; 193(4): 430-441, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36690077

RESUMEN

Ferrostatin-1 (Fer-1), an inhibitor of ferroptosis, is implicated in intervertebral disc degeneration (IDD). The current study explored the role of Fer-1 in IDD via the toll-like receptor 4 (TLR4)/NF-κB signaling pathway. IDD-related gene expression microarray GSE124272 and high-throughput sequencing data set GSE175710 were obtained through the Gene Expression Omnibus database. Differentially expressed genes in IDD were identified, followed by implementation of protein-protein interaction network analysis and receiver operating characteristic curve analysis. The main pathways in IDD were obtained through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes functional analyses, and target genes of Fer-1 were obtained through PubChem and PharmMapper websites. Finally, GPX4, FTH, and TLR4 expression was determined in a IDD rat model. Three key co-expression modules involved in IDD were obtained through Weighted Gene Co-Expression Network Analysis. Thirteen differentially expressed genes were found to be associated with IDD, and eight key genes (TLR4, BCL2A1, CXCL1, IL1R1, NAMPT, SOCS3, XCL1, and IRAK3) were found to affect IDD. These eight key genes had the diagnostic potential for IDD. The NF-κB signaling pathway was shown to play a predominant role in IDD development. Network pharmacologic analysis indicated a role of Fer-1 in suppressing ferroptosis and ameliorating IDD via the TLR4/NF-κB signaling pathway, which was verified by an in vivo animal experiment. The study showed that Fer-1 down-regulates TLR4 to inactivate NF-κB signaling pathway, suppressing ferroptosis and ultimately alleviating IDD in rats.


Asunto(s)
Degeneración del Disco Intervertebral , Disco Intervertebral , Ratas , Animales , FN-kappa B/metabolismo , Degeneración del Disco Intervertebral/genética , Degeneración del Disco Intervertebral/metabolismo , Receptor Toll-Like 4/genética , Receptor Toll-Like 4/metabolismo , Transducción de Señal/fisiología
2.
J Nanobiotechnology ; 22(1): 556, 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39267105

RESUMEN

METHODS: Single-cell transcriptomics and high-throughput transcriptomics were used to screen factors significantly correlated with intervertebral disc degeneration (IDD). Expression changes of CFIm25 were determined via RT-qPCR and Western blot. NP cells were isolated from mouse intervertebral discs and induced to degrade with TNF-α and IL-1ß. CFIm25 was knocked out using CRISPR-Cas9, and CFIm25 knockout and overexpressing nucleus pulposus (NP) cell lines were generated through lentiviral transfection. Proteoglycan expression, protein expression, inflammatory factor expression, cell viability, proliferation, migration, gene expression, and protein expression were analyzed using various assays (alcian blue staining, immunofluorescence, ELISA, CCK-8, EDU labeling, transwell migration, scratch assay, RT-qPCR, Western blot). The GelMA-HAMA hydrogel loaded with APET×2 polypeptide and sgRNA was designed, and its effects on NP regeneration were assessed through in vitro and mouse model experiments. The progression of IDD in mice was evaluated using X-ray, H&E staining, and Safranin O-Fast Green staining. Immunohistochemistry was performed to determine protein expression in NP tissue. Proteomic analysis combined with in vitro and in vivo experiments was conducted to elucidate the mechanisms of hydrogel action. RESULTS: CFIm25 was upregulated in IDD NP tissue and significantly correlated with disease progression. Inhibition of CFIm25 improved NP cell degeneration, enhanced cell proliferation, and migration. The hydrogel effectively knocked down CFIm25 expression, improved NP cell degeneration, promoted cell proliferation and migration, and mitigated IDD progression in a mouse model. The hydrogel inhibited inflammatory factor expression (IL-6, iNOS, IL-1ß, TNF-α) by targeting the p38/NF-κB signaling pathway, increased collagen COLII and proteoglycan Aggrecan expression, and suppressed NP degeneration-related factors (COX-2, MMP-3). CONCLUSION: The study highlighted the crucial role of CFIm25 in IDD and introduced a promising therapeutic strategy using a porous spherical GelMA-HAMA hydrogel loaded with APET×2 polypeptide and sgRNA. This innovative approach offers new possibilities for treating degenerated intervertebral discs.


Asunto(s)
Hidrogeles , Degeneración del Disco Intervertebral , Núcleo Pulposo , Péptidos , Regeneración , Animales , Hidrogeles/química , Núcleo Pulposo/metabolismo , Ratones , Degeneración del Disco Intervertebral/terapia , Regeneración/efectos de los fármacos , Péptidos/química , Péptidos/farmacología , Disco Intervertebral , Humanos , Proliferación Celular/efectos de los fármacos , Masculino , Ratones Endogámicos C57BL , Movimiento Celular/efectos de los fármacos
3.
Sheng Li Xue Bao ; 75(1): 59-68, 2023 Feb 25.
Artículo en Zh | MEDLINE | ID: mdl-36859835

RESUMEN

The purpose of this study was to explore the effect and mechanism of dihydromyricetin (DHM) on Parkinson's disease (PD)-like lesions in type 2 diabetes mellitus (T2DM) rats. The T2DM model was established by feeding Sprague Dawley (SD) rats with high-fat diet and intraperitoneal injection of streptozocin (STZ). The rats were intragastrically administered with DHM (125 or 250 mg/kg per day) for 24 weeks. The motor ability of the rats was measured by balance beam experiment, the changes of dopaminergic (DA) neurons and the expression of autophagy initiation related protein ULK1 in the midbrains of the rats were detected by immunohistochemistry, and the protein expression levels of α-synuclein (α-syn), tyrosine hydroxylase (TH), as well as AMPK activation level, in the midbrains of the rats were detected by Western blot. The results showed that, compared with normal control, the rats with long-term T2DM exhibited motor dysfunction, increased α-syn aggregation, down-regulated TH protein expression, decreased number of DA neurons, declined activation level of AMPK, and significantly down-regulated ULK1 expression in the midbrain. DHM (250 mg/kg per day) treatment for 24 weeks significantly improved the above PD-like lesions, increased AMPK activity, and up-regulated ULK1 protein expression in T2DM rats. These results suggest that DHM may improve PD-like lesions in T2DM rats by activating AMPK/ULK1 pathway.


Asunto(s)
Diabetes Mellitus Tipo 2 , Enfermedad de Parkinson , Ratas , Animales , Ratas Sprague-Dawley , Proteínas Quinasas Activadas por AMP , Homólogo de la Proteína 1 Relacionada con la Autofagia
4.
Sheng Li Xue Bao ; 74(5): 773-782, 2022 Oct 25.
Artículo en Zh | MEDLINE | ID: mdl-36319100

RESUMEN

The objective of this study was to investigate the cardiac protective effect of low-to-moderate intensity exercise training and the role of the Wnt signaling pathway in spontaneously hypertensive rats (SHR). SHR and Wistar-Kyoto (WKY) rats were randomly divided into 5 groups, namely hypertensive control (SHR-S), hypertensive plus exercise training (SHR-E), normal blood pressure control (WKY-S), normal blood pressure plus exercise training (WKY-E) and SHR-E plus Wnt agonist (SHR-E-Wnt). The rats in SHR-E and WKY-E groups underwent low-to-moderate intensity swimming for 16 weeks, and the rats in SHR-E-Wnt group were injected with Wnt agonist 1 through tail vein 4 weeks before the end of swimming. The blood pressure of rats was measured every week. After exercise training, the left ventricular wall thickness and ejection function were measured by ultrasound cardiogram, myocardial structure and collagen fiber changes were observed by HE staining and Masson staining, and the expression levels of ß-catenin and Dishevelled-1 (DVL-1) mRNA and protein in left ventricular myocardium were detected by real-time fluorescence quantitative PCR and Western blot, respectively. The results showed that the body weight was decreased (P < 0.05), blood pressure was increased (P < 0.01), heart weight and ventricular wall thickness were increased (P < 0.01), and the left ventricular ejection function was decreased (P < 0.05) in SHR-S group compared with those in WKY-S group. In addition, the heart structure was damaged, collagen fibers were significantly increased, and the mRNA and protein expressions of ß-catenin and DVL-1 in the left ventricle were significantly up-regulated in SHR-S group compared with those in WKY-S group (P < 0.01). Compared with those in SHR-S group, the body weight of SHR-E group did not change significantly (P > 0.05), but the blood pressure was decreased (P < 0.01), heart weight and ventricular wall thickness were diminished, ejection function was increased (P < 0.01), myocardial structure injury was significantly improved, collagen fibers were significantly reduced, and mRNA and protein expression levels of ß-catenin and DVL-1 in the left ventricle were significantly down-regulated (P < 0.01) in SHR-E group. Importantly, exercise-induced antihypertensive and cardioprotective effects in SHR were blunted by Wnt agonist. These results suggest that low-to-moderate intensity exercise training exerts cardioprotective effects in SHR, possibly through inhibiting the Wnt signaling pathway.


Asunto(s)
Condicionamiento Físico Animal , beta Catenina , Ratas , Animales , Ratas Endogámicas SHR , beta Catenina/metabolismo , Ratas Endogámicas WKY , Vía de Señalización Wnt , ARN Mensajero/metabolismo , Colágeno/metabolismo , Peso Corporal
5.
Yi Chuan ; 43(8): 737-746, 2021 Aug 20.
Artículo en Zh | MEDLINE | ID: mdl-34413014

RESUMEN

Existing research has shown that there are a large amount of non-coding RNAs (ncRNAs) in organisms. Short open reading frames (sORFs) abundantly exist in molecular sequences inaccurately annotated as ncRNAs. Several sORFs can be transcribed and translated into evolutionarily conserved micropeptides, which were ignored in previous studies due to short sequence lengths and the limitations of research techniques. To date, sORF-encoded micropeptides with various functions have been found to play important roles in regulating vital biological activities. This article reviews the functional micropeptides which have been found in recent years, introduces the new micropeptide designated as MIAC that we have discovered and describes the related technologies for mining potential micropeptides, thereby providing insights and references for new micropeptide discovery for researchers.


Asunto(s)
Péptidos , ARN no Traducido , Sistemas de Lectura Abierta/genética , Péptidos/genética
6.
Biomed Eng Online ; 19(1): 83, 2020 Nov 11.
Artículo en Inglés | MEDLINE | ID: mdl-33176808

RESUMEN

BACKGROUND: As a serious clinical disease, ischemic stroke is usually detected through magnetic resonance imaging and computed tomography. In this study, a noninvasive, non-contact, real-time continuous monitoring system was constructed on the basis of magnetic induction phase shift (MIPS) technology. The "thrombin induction method", which conformed to the clinical pathological development process of ischemic stroke, was used to construct an acute focal cerebral ischemia model of rabbits. In the MIPS measurement, a "symmetric cancellation-type" magnetic induction sensor was used to improve the sensitivity and antijamming capability of phase detection. METHODS: A 24-h MIPS monitoring experiment was carried out on 15 rabbits (10 in the experimental group and five in the control group). Brain tissues were taken from seven rabbits for the 2% triphenyl tetrazolium chloride staining and verification of the animal model. RESULTS: The nonparametric independent-sample Wilcoxon rank sum test showed significant differences (p < 0.05) between the experimental group and the control group in MIPS. Results showed that the rabbit MIPS presented a declining trend at first and then an increasing trend in the experimental group, which may reflect the pathological development process of cerebral ischemic stroke. Moreover, TTC staining results showed that the focal cerebral infarction area increased with the development of time CONCLUSIONS: Our experimental study indicated that the MIPS technology has a potential ability of differentiating the development process of cytotoxic edema from that of vasogenic edema, both of which are caused by cerebral ischemia.


Asunto(s)
Hemorragia Cerebral/fisiopatología , Conductividad Eléctrica , Fenómenos Magnéticos , Monitoreo Fisiológico/métodos , Enfermedad Aguda , Animales , Conejos , Factores de Tiempo
7.
Yi Chuan ; 41(3): 234-242, 2019 Mar 20.
Artículo en Zh | MEDLINE | ID: mdl-30872259

RESUMEN

The development of second-generation sequencing (NGS) technology is providing numerous data which shifts the focus of cancer research from the sequencing of multi-species to the analysis and comparison of select data via high-throughput sequencing. The NGS also facilitates the diversity of available genetic data analysis methods, the constant optimization and innovation of analytical approaches for high-throughput genomics as well as the rapid development of genetic data mining and analysis models. The Cancer Genome Atlas (TCGA) database is a direct result of this work. The TCGA database provides a comprehensive record of genetic data collected from a tumor patient's sample, including its DNA sequence, transcriptional information, epigenetic modification and related. This review elaborates the latest progress in both the mining algorithm and analysis methods for tumor genomics. Specially, we introduce and review the TCGA database and data analysis approaches while demonstrating its applicability using representative cases. This review may shed light on new tumor-related targets discovery for researchers by means of bid data.


Asunto(s)
Bases de Datos de Ácidos Nucleicos , Secuenciación de Nucleótidos de Alto Rendimiento , Neoplasias/genética , Humanos , Análisis de Secuencia de ADN
8.
Yi Chuan ; 40(11): 1039-1043, 2018 Nov 20.
Artículo en Zh | MEDLINE | ID: mdl-30465537

RESUMEN

Omics data in life and health sciences are of fundamental significance for scientific research and biomedical technology development. However, there is yet to be a platform for biological data management and sharing in China, making it difficult to meet the development needs of biomedical and related fields and consequently leading to severe issues in big data management, sharing and translation. To address these issues, Beijing Institute of Genomics (BIG) of Chinese Academy of Sciences founded the BIG Data Center (BIGD) in 2016, which is dedicated to establish a biological big data management platform and multi-omics databases, with a particular focus on national population healthcare and important strategic biological resources. In this paper, we describe core database resources in BIGD, including GSA (Genome Sequence Archive), GWH (Genome Warehouse), GVM (Genome Variation Map), GEN (Gene Expression Nebulas), MethBank (Methylation Bank), BioCode and Science Wikis. Taken together, all these resources provide a series of services for data deposition, integration and sharing, laying solid foundations for enhancing national biological science data management and further promoting the construction of national bioinformatics center.


Asunto(s)
Macrodatos , Genómica , China , Biología Computacional/instrumentación , Biología Computacional/organización & administración , Minería de Datos , Bases de Datos Genéticas , Genómica/instrumentación , Genómica/organización & administración , Humanos
9.
Biochim Biophys Acta ; 1851(2): 172-83, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25463482

RESUMEN

Erythrocytes and megakaryocytes (MK) are derived from a common progenitor that undergoes lineage specification. Lysophosphatidic acid (LPA), a lipid growth factor was previously shown to be a regulator for erythropoietic process through activating LPA receptor 3 (LPA3). However, whether LPA affects megakaryopoiesis remains unclear. In this study, we used K562 leukemia cell line as a model to investigate the roles of LPA in MK differentiation. We demonstrated that K562 cells express both LPA2 and LPA3, and the expression levels of LPA2 are higher than LPA3. Treatment with phorbol 12-myristate 13-acetate, a commonly used inducer of megakaryopoiesis, reciprocally regulates the expressions of LPA2 and LPA3. By pharmacological blockers and knockdown experiments, we showed that activation of LPA2 suppresses whereas, LPA3 promotes megakaryocytic differentiation in K562. The LPA2-mediated inhibition is dependent on ß-catenin translocation, whereas reactive oxygen species (ROS) generation is a downstream signal for activation of LPA3. Furthermore, the hematopoietic transcriptional factors GATA-1 and FLI-1, appear to be involved in these regulatory mechanisms. Taken together, our results suggested that LPA2 and LPA3 may function as a molecular switch and play opposing roles during megakaryopoiesis of K562 cells.


Asunto(s)
Leucemia Eritroblástica Aguda/metabolismo , Megacariocitos/metabolismo , Receptores del Ácido Lisofosfatídico/metabolismo , Trombopoyesis , Factor de Transcripción GATA1/metabolismo , Humanos , Integrina beta3/metabolismo , Células K562 , Leucemia Eritroblástica Aguda/genética , Megacariocitos/efectos de los fármacos , Proteínas de Microfilamentos/metabolismo , Interferencia de ARN , Especies Reactivas de Oxígeno/metabolismo , Receptores Citoplasmáticos y Nucleares/metabolismo , Receptores del Ácido Lisofosfatídico/antagonistas & inhibidores , Receptores del Ácido Lisofosfatídico/genética , Transducción de Señal , Acetato de Tetradecanoilforbol/farmacología , Trombopoyesis/efectos de los fármacos , Factores de Tiempo , Transactivadores , Transfección , beta Catenina/metabolismo
10.
Oxid Med Cell Longev ; 2022: 8983667, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35847582

RESUMEN

Objective: It has been reported that bone marrow mesenchymal stem cells (BMSCs) are a potential source of autologous stem cells to support the nucleus pulposus (NP) regeneration in intervertebral disc degeneration (IDD). Herein, we aim to study the mechanism underlying the effects of BMSC-derived extracellular vesicles (BMSC-EVs) on nucleus pulposus cells (NPCs) in IDD. Methods: EVs were isolated from BMSCs. An IDD model was surgically established in C57BL/6J mice. NPCs were exposed to tBHP to establish an IDD cell model. RNA sequencing was performed to identify differentially expressed circRNAs in NP tissues harvested from mice with IDD. Interactions among circ_0050205, miR-665, and GPX4 were validated, and different interventions were used to study the roles of these molecules in NPC biological functions. Results: BMSC-EVs promoted NPC survival and inhibited NPC apoptosis and extracellular matrix (ECM) degradation. circ_0050205 expression was downregulated in the NP tissues of IDD mice, and BMSC-EVs facilitated NPC survival and suppressed ECM degradation in NPCs by transferring circ_0050205. circ_0050205 sponged miR-665 and upregulated GPX4 expression. BMSC-EVs expressing circ_0050205 promoted NPC survival-inhibited ECM degradation in NPCs and alleviated IDD in mice via the miR-665/GPX4 axis. Conclusion: In conclusion, BMSC-EVs promoted NPC survival-inhibited ECM degradation in NPCs and attenuated IDD progression via the circ_0050205/miR-665/GPX4 axis.


Asunto(s)
Vesículas Extracelulares , Degeneración del Disco Intervertebral , Células Madre Mesenquimatosas , MicroARNs , Animales , Apoptosis , Matriz Extracelular/metabolismo , Vesículas Extracelulares/metabolismo , Degeneración del Disco Intervertebral/genética , Degeneración del Disco Intervertebral/metabolismo , Células Madre Mesenquimatosas/metabolismo , Ratones , Ratones Endogámicos C57BL , MicroARNs/genética , MicroARNs/metabolismo
11.
Mitochondrial DNA B Resour ; 5(1): 709-710, 2020 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-33366714

RESUMEN

Mediterranean buffalo (Bubalus bubalis Linnaeus, 1758 breed Mediterranean, MEB) is one of the best milk-producing breeds in river-type buffaloes in the world. It is the first time that the complete mitochondrial genome sequence of the MEB was reported. The total length of the mtDNA is 16,357 bp, It contains the typical structure, including 22 transfer RNA genes, 2 ribosomal RNA genes, 13 protein-coding genes and 1 non-coding control region (D-loop region). The overall composition of the mtDNA was estimated to be 33.10% for A, 26.44% for T, 26.57% for C and 13.89% for G, in the order A > C > T > G feature occurs in the MEB. Phylogenetic analyses using N-J computational algorithms showed that the analyzed 18 ruminantia species are divided into four major clades: Bovidae, Cervidae, Giraffidae and Atilocapridae. In addition, our work confirmed that MEB and Nili-Ravi buffalo (NRB) have a close genetic relationship with fellow tribal members Murrah buffalo. Meanwhile, we also found that MEB and NRB have highly similar genetic relationship.

12.
Sci Rep ; 10(1): 16441, 2020 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-33020557

RESUMEN

Micro-electro-mechanical system (MEMS) gyroscopes have numerous potential applications including guidance, robotics, tactical-grade navigation, and automotive applications fields. The methods with ability of the weak Coriolis force detection are critical for MEMS gyroscopes. In this paper, we presented a design of MEMS gyroscope based on the tunneling magneto-resistance effect with higher detection sensitivity. Of all these designed parameters, the structural, magnetic field, and magneto-resistance sensitivity values reach to 21.6 nm/°/s, 0.0023 Oe/nm, and 29.5 mV/Oe, thus, with total sensitivity of 1.47 mV/°/s. Multi-bridge circuit method is employed to suppress external magnetic interference and avoid the integration error of the TMR devices effectively. The proposed tunneling magneto-resistive micro-gyroscope shows a possibility to make an inertial grade MEMS gyroscope in the future.

13.
Mitochondrial DNA B Resour ; 5(1): 461-462, 2020 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-33366602

RESUMEN

Nili-Ravi buffalo (Bubalus bubalis Linnaeus, 1758 breed Nili-Ravi, NRB) is a famous water buffalo breed in the world. It is the first time that the complete mitochondrial genome sequence of the NRB was reported. The total length of the mtDNA is 16,356 bp, It contains the typical structure, including 22 transfer RNA genes, 2 ribosomal RNA genes, 13 protein-coding genes, and 1 non-coding control region (D-loop region). The overall composition of the mtDNA was estimated to be 33.11% for A, 26.45% for T, 26.55% for C, and 13.89% for G. Phylogenetic analyses using neighbor-joining (N-J) computational algorithms showed that the analyzed 18 Ruminantia species are divided into four major clades: Bovidae, Cervidae, Giraffidae, and Atilocapridae. In addition, our work confirmed that NRB has a close genetic relationship with B. bubalis isolate India 4.

14.
Mitochondrial DNA B Resour ; 5(1): 713-714, 2020 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-33366716

RESUMEN

Fuzhong buffalo (Bubalus bubalis Linnaeus, 1758 breed Fuzhong, FB) is one of the famous indigenous breeds of buffalo in China. It is the first time that the complete mitochondrial genome sequence of the FB was reported. The total length of the mtDNA is 16,363 bp, It contains the typical structure, including 22 transfer RNA genes, two ribosomal RNA genes, 13 protein-coding genes and one non-coding control region (D-loop region). The overall composition of the mtDNA was estimated to be 32.98% for A, 26.34% for T, 26.70% for C and 13.98% for G. Phylogenetic analyses using N-J computational algorithms showed that the analyzed 19 ruminantia species are divided into four major clades: Bovidae, Cervidae, Giraffidae and Atilocapridae. In addition, our work confirmed that FB and Murrah buffalo (MB) have a close genetic relationship with fellow tribal members Nili-Ravi buffalo and Mediterranean buffalo. Meanwhile, we also found that FB and MB have a highly similar genetic relationship.

15.
Mitochondrial DNA B Resour ; 5(1): 432-433, 2020 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-33426275

RESUMEN

Murrah buffalo (Bubalus bubalis Linnaeus, 1758 breed Murrah, MB) is a most productive water buffalo breed. It is the first time that the complete mitochondrial genome sequence of the MB was reported. The total length of the mtDNA is 16,359 bp, It contains the typical structure, including 22 transfer RNA genes, 2 ribosomal RNA genes, 13 protein-coding genes and 1 non-coding control region (D-loop region). The overall composition of the mtDNA was estimated to be 33.00% for A, 26.32% for T, 26.71% for C and 13.97% for G. Phylogenetic analyses using N-J computational algorithms showed that the analyzed 18 Ruminantia species are divided into four major clades: Bovidae, Cervidae, Giraffidae and Atilocapridae. In addition, our work confirmed that MB and Bubalus bubalis isolate India 4 have a close genetic relationship.

16.
Org Lett ; 20(21): 6616-6621, 2018 11 02.
Artículo en Inglés | MEDLINE | ID: mdl-30215527

RESUMEN

A new class of chiral N-sulfonyl bisimidazoline (Bim) ligands have been designed, prepared, and applied in Pd(II)-catalyzed asymmetric addition of arylboronic acids to isatin-derived N-Boc ketimines. The combination of Pd(OCOCF3)2 and N-tosyl Bim ligand shows high catalytic activity and excellent asymmetric induction, enabling asymmetric addition to offer α-tertiary amines with generally good to high yields and excellent enantioselectivity (up to 96% yield, 96% ee). This asymmetric Pd(II) catalysis can tolerate air conditions, providing a practical and operationally simple protocol toward the construction of an enantioenriched α-tertiary stereocenter.

17.
Taiwan J Obstet Gynecol ; 57(5): 722-725, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-30342659

RESUMEN

OBJECTIVE: Previous study has demonstrated that EphA2 is a biomarker of mesenchymal stem cells (MSCs) from human placenta or umbilical cord and is able to distinguish MSCs from fibroblasts. In this study, we further examine the potential efficacy of EphA2+ human umbilical cord-derived MSCs (hUC-MSCs). MATERIALS AND METHODS: MSCs specific markers, EphA2 and CD146 expression on the surface of hUC-MSCs were determined by flow cytometry analysis. Quantitative real time polymerase chain reaction was used to examine pro-fibrotic gene expression of TGF-ß1-stimulated lung fibroblast (MRC-5 cells). On the other hand, ELISA was used to analyze the content of pro-inflammatory cytokines (TNF-ɑ; and IP-10) in the LPS-activated macrophages culture supernatant. RESULTS: The pro-fibrotic gene (TGF-ß1, CTGF, fibronectin, collagen I and TIMP-1) expression in TGF-ß1-activated MRC-5 cells and the pro-inflammatory cytokines (TNF-ɑ and IP-10) in the LPS-activated macrophages culture supernatant were both attenuated when in present of EphA2+ hUC-MSCs. Moreover, once EphA2+ hUC-MSCs treated with prostaglandin E2 specific inhibitor NS-398, both anti-fibrotic and anti-inflammatory effects of EphA2+ hUC-MSCs were abolished. CONCLUSION: EphA2+ hUC-MSCs possess immunomodulatory and anti-fibrotic properties, and PGE2 plays an important role in these activities. This implies that EphA2+ hUC-MSCs have potentially effectiveness for treatment of acute inflammatory and chronic fibrotic lung diseases.


Asunto(s)
Biomarcadores/análisis , Dinoprostona/metabolismo , Efrina-A2/análisis , Células Madre Mesenquimatosas/química , Células Madre Mesenquimatosas/fisiología , Cordón Umbilical/citología , Antígeno CD146/análisis , Separación Celular , Femenino , Fibroblastos/metabolismo , Fibrosis/genética , Fibrosis/prevención & control , Citometría de Flujo , Expresión Génica , Humanos , Inmunomodulación , Inflamación/prevención & control , Macrófagos/metabolismo , Células Madre Mesenquimatosas/microbiología , Receptor EphA2 , Células THP-1
18.
Stem Cells Dev ; 27(3): 216-224, 2018 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-29239275

RESUMEN

Lysophosphatidic acid (LPA) is a membrane-derived lysophospholipid that exists in the plasma and platelets. It exerts its functions through activation of various LPA receptors (LPARs), which belong to the family of G protein-coupled receptors. Activation of LPARs has important roles in stem cell differentiation. However, how LPA affects human hematopoietic stem cell (HSC) differentiation remains elusive. In our previous studies, we have suggested that LPA receptor 2 (LPA2) and LPA receptor 3 (LPA3) play opposing roles and may act as a molecular switch during megakaryocytic differentiation in K562 cells. In this study, human CD34+ HSCs and zebrafish are adopted to investigate the roles of LPA3 during megakaryopoiesis/thrombopoiesis in vitro and in vivo. Our results show that LPAR3 mRNA expression level is decreased upon induction by thrombopoietin and stem cell factor in human HSCs. Using pharmacological activators and shRNA knockdown experiments, we demonstrate that activation of LPA3 inhibits megakaryopoiesis in human HSCs. In addition, pharmacological activation of LPA3 suppressed thrombopoiesis in zebrafish. Furthermore, blockage of LPA3 translation by morpholino increased the number of CD41-GFP+ cells in Tg(CD41:eGFP) zebrafish. Moreover, the mRNA expression level of zCD41 increased significantly in LPA3-knockout zebrafish. These results clarify the negative role of LPA3 during megakaryopoiesis and provide important information for potential treatments of related diseases, such as megakaryopenia.


Asunto(s)
Células Madre Hematopoyéticas/metabolismo , Megacariocitos/metabolismo , Receptores del Ácido Lisofosfatídico/metabolismo , Trombopoyesis , Proteínas de Pez Cebra/metabolismo , Pez Cebra/metabolismo , Animales , Humanos , Receptores del Ácido Lisofosfatídico/antagonistas & inhibidores , Receptores del Ácido Lisofosfatídico/genética , Pez Cebra/genética , Proteínas de Pez Cebra/genética
19.
Sci Rep ; 6: 27050, 2016 05 31.
Artículo en Inglés | MEDLINE | ID: mdl-27244685

RESUMEN

Lysophosphatidic acid (LPA), a growth factor-like phospholipid, regulates numerous physiological functions, including cell proliferation and differentiation. In a previous study, we have demonstrated that LPA activates erythropoiesis by activating the LPA 3 receptor subtype (LPA3) under erythropoietin (EPO) induction. In the present study, we applied a pharmacological approach to further elucidate the functions of LPA receptors during red blood cell (RBC) differentiation. In K562 human erythroleukemia cells, knockdown of LPA2 enhanced erythropoiesis, whereas knockdown of LPA3 inhibited RBC differentiation. In CD34(+) human hematopoietic stem cells (hHSC) and K526 cells, the LPA3 agonist 1-oleoyl-2-methyl-sn-glycero-3-phosphothionate (2S-OMPT) promoted erythropoiesis, whereas the LPA2 agonist dodecyl monophosphate (DMP) and the nonlipid specific agonist GRI977143 (GRI) suppressed this process. In zebrafish embryos, hemoglobin expression was significantly increased by 2S-OMPT treatment but was inhibited by GRI. Furthermore, GRI treatment decreased, whereas 2S-OMPT treatment increased RBC counts and amount of hemoglobin level in adult BALB/c mice. These results indicate that LPA2 and LPA3 play opposing roles during RBC differentiation. The pharmacological activation of LPA receptor subtypes represent a novel strategies for augmenting or inhibiting erythropoiesis.


Asunto(s)
Diferenciación Celular/efectos de los fármacos , Eritropoyesis/efectos de los fármacos , Células Madre Hematopoyéticas/efectos de los fármacos , Lisofosfolípidos/metabolismo , Receptores del Ácido Lisofosfatídico/genética , Animales , Embrión no Mamífero , Eritrocitos/citología , Eritrocitos/efectos de los fármacos , Eritrocitos/metabolismo , Eritropoyesis/genética , Eritropoyetina/farmacología , Regulación de la Expresión Génica , Células Madre Hematopoyéticas/citología , Células Madre Hematopoyéticas/metabolismo , Hemoglobinas/antagonistas & inhibidores , Hemoglobinas/biosíntesis , Hemoglobinas/genética , Humanos , Células K562 , Lisofosfolípidos/farmacología , Ratones , Ratones Endogámicos BALB C , Organofosfatos/farmacología , Organotiofosfatos/farmacología , Ácidos Fosfatidicos/farmacología , Isoformas de Proteínas/agonistas , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Receptores del Ácido Lisofosfatídico/agonistas , Receptores del Ácido Lisofosfatídico/metabolismo , Pez Cebra
20.
Pak J Biol Sci ; 16(18): 969-75, 2013 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-24502157

RESUMEN

It is undeniable that environmental sonic vibration can affect our emotions and mood, but so far the study of physical stimuli provoked by audible wave on single cells has been rarely concerned. To investigate the response of E. coli to audible wave exposure, the growth status and alterations in antioxidant enzyme activity were studied in liquid culture. The data showed that the growth of E. coli was promoted in the treatments of different frequencies sound wave. The most significant effect on growth promotion appeared when sound wave was maintained at 100 dB and 5000 Hz. Simultaneously, sonic vibration evoked significantly increases the level of total protein content contents. And the changes of activities of Super Oxide Dismutase (SOD) and catalase (CAT) were observed obviously. The results suggested that the growth promotion effect of audible sound may be non-linear and shows obvious frequency and intensity peculiarities. Moreover, the increase in activity of antioxidant enzymes implied that a number of active oxygen species generated in bacterial cell under the exposure of audible sound. We speculate that the audible sound may cause a secondary oxidative stress. Further studies are needed to elucidate the mechanisms of active oxygen species generation induced by audible sound.


Asunto(s)
Escherichia coli/crecimiento & desarrollo , Mecanotransducción Celular , Sonido , Antioxidantes/metabolismo , Catalasa/metabolismo , Escherichia coli/enzimología , Proteínas de Escherichia coli/metabolismo , Estrés Oxidativo , Presión , Especies Reactivas de Oxígeno/metabolismo , Superóxido Dismutasa/metabolismo , Vibración
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