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Fourteen compounds, including rubiprasin D (1), rubiprasin B (2), rubiprasin C (3), oleanolic acid (4), methyl-5-hydroxy-dinaphtho[1, 2-2'3']furan-7, 12-dione-6-carboxylate (5), rubioncolin C (6), mollugin (7), furomollugin (8), 3-amino-2-methoxycarbonyl-1, 4-naphthoquinone (9), 1-hydroxy-2-methyl-9, 10-anthraquinone (10), 2-hydroxy-6-methyl-9, 10-anthraquinone (11), 1, 4-dihydroxy-2-hydroxymethyl-9, 10-anthraquinone (12), 2-hydroxy-1-methoxy-9, 10-anthraquinone (13), and 1-hydroxy-2-methoxy-6-methyl-9, 10-anthraquinone(14), were isolated from the methanol extract of the roots and rhizomes of Rubia oncotricha using various column chromatographies. Their structures were mainly determined on basis of NMR and MS spectroscopic data analyses. Among them, 1 is a new oleanane triterpene, and compounds 2-5, 9 and 11-13 were obtained from this plant for the first time. Cytotoxic and nematicidal activities of all these compounds were evaluated, and the results showed that only 4, 6, 11 and 12 exhibited cytotoxicities against A549, SGC-7901 and HeLa cancer cell lines. The IC50 of 6 were 19.42, 2.74, 8.07 µmol·L⻹, respectively.
Asunto(s)
Naftoquinonas , Rubia , Estructura Molecular , Extractos Vegetales , Raíces de Plantas , RizomaRESUMEN
Cyclopeptide RA-V has potent anti-tumor and anti-angiogenic activities, but its potential anti-metastatic activity is unknown. Cancer cells acquire invasive ability to degrade and adhere to extracellular matrix (ECM), allowing them to migrate to adjacent tissues and ultimately metastasize. Hence, the present study aimed to investigate the effects of RA-V on cell adhesion, migration, invasion and matrix degradation, and its underlying mechanism in two human breast cancer cell lines MCF-7 (ER-positive) and MDA-MB-231 (ER-negative). Our results demonstrated that RA-V (12.5 nM) can significantly inhibit breast cancer cell adhesion and migration via interfering cofilin signaling and chemokine receptors involved in cell migration. RA-V reduced the expressions of vascular intracellular adhesion molecule (VCAM), intracellular adhesion molecule (ICAM), focal adhesion kinase (FAK) and integrins. The activities and expressions of matrix metalloproteinases (MMPs), tissue inhibitors of matrix metalloproteinases (TIMPs) and urokinase-type of plasminogen activator (uPA) were also inhibited by RA-V. Furthermore, RA-V inhibits the expressions of EGFR, PI3K/AKT and NF-κB signaling molecules, and reduces the binding of ß-estradiol to ER via affecting binding ability of ER in MCF-7 cells. RA-V inhibits breast cancer cell migration, adhesion and ECM degradation in vitro, implying that RA-V is a potential anti-metastatic agent in breast cancer, and likely acts via PI3K/AKT and NF-κB signaling pathways in both ER-positive and ER-negative breast cancer cells.
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Antineoplásicos Fitogénicos/farmacología , Neoplasias de la Mama/patología , Péptidos Cíclicos/farmacología , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Adhesión Celular/efectos de los fármacos , Línea Celular Tumoral , Femenino , Células HeLa , Humanos , Células MCF-7 , FN-kappa B/metabolismo , Invasividad Neoplásica , Proteína Oncogénica v-akt/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Receptores de Estrógenos/genética , Receptores de Estrógenos/metabolismo , Transducción de Señal/efectos de los fármacosRESUMEN
Three new labdane diterpenes, hedylongnoids A (1), B (2) and C (3), were isolated from the rhizomes of Hedychium longipetalum, together with three known ones yunnancoronarin A (4), hedyforrestin C (5) and hedyforrestin B (6). Their structures were established by spectroscopic analysis, including 2D-NMR spectroscopic techniques. Compounds 1-6 exhibited inhibitory effects against nitric oxide (NO) production in LPS and IFN-γ-induced RAW 264.7 murine macrophages with IC50 values ranging from 0.56 to 7.50 µg/ml, and 3-6 showed cytotoxicities against cancer cell lines SGC-7901 and Hela with IC50 values ranging from 6.21 to 14.53 µg/ml and from 6.58 to 14.83 µg/ml, respectively.
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Diterpenos/farmacología , Óxido Nítrico/biosíntesis , Zingiberaceae/química , Animales , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Diterpenos/química , Diterpenos/aislamiento & purificación , Relación Dosis-Respuesta a Droga , Células HeLa , Humanos , Interferón gamma/metabolismo , Lipopolisacáridos/antagonistas & inhibidores , Lipopolisacáridos/farmacología , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Ratones , Estructura Molecular , Relación Estructura-ActividadRESUMEN
Highly pure Rh2P nanoparticles on N,P-codoped carbon were synthesized by a simple "mix-and-pyrolyze" method using one kind of low-cost nucleotide as the carbon, nitrogen and phosphorus source, which exhibits excellent bifunctional activity for the hydrogen reduction and hydrazine oxidation reactions, achieving energy-efficient hydrogen production.
RESUMEN
Two new coumarins, clauexcavatins A (1) and B (2), along with seven known ones (3-9), were isolated from the roots of Clausena excavata Burm. f. (Rutaceae). Their structures were elucidated on the basis of spectral data.
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Clausena/química , Cumarinas/aislamiento & purificación , Medicamentos Herbarios Chinos/aislamiento & purificación , Carbazoles/química , Carbazoles/aislamiento & purificación , Cumarinas/química , Medicamentos Herbarios Chinos/química , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Raíces de Plantas/químicaRESUMEN
Thyroid cancer is the most common malignant neoplasm within the endocrine system and the field of head and neck surgery. Although the majority of thyroid cancers, more than 90%, are well-differentiated thyroid carcinomas with a favourable prognosis, the escalating incidence of this disease has contributed to an increasing number of patients with a propensity for recurrent disease, rapid disease progression, and poor or no response to conventional treatments. These clinical challenges are commonly attributed to alterations in key thyroid oncogenes or signaling pathways, thereby initiating tumour cell dedifferentiation events, accompanied by reduced or virtually absent expression of the sodium/iodine symporter (NIS). As a result, the disease evolves into iodine-refractory differentiated thyroid cancer (RAIR-DTC), an entity that is insensitive to conventional radioiodine therapy. Despite being classified as a differentiated thyroid cancer, RAIR-DTC has an extremely poor clinical prognosis, with a 10-year survival rate of less than 10%. Therefore, it is of paramount importance to comprehensively elucidate the underlying pathogenesis of RAIR-DTC and provide specific targeted interventions. As the pathogenic mechanisms of RAIR-DTC remain elusive, here we aim to review recent advances in understanding the pathogenesis of RAIR-DTC and provide valuable insights for the development of future molecularly targeted therapeutic approaches.
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Adenocarcinoma , Yodo , Neoplasias de la Tiroides , Humanos , Yodo/uso terapéutico , Radioisótopos de Yodo/uso terapéutico , Neoplasias de la Tiroides/patología , Adenocarcinoma/tratamiento farmacológico , Transducción de SeñalRESUMEN
Natural cyclopeptides are hot spots in chemical and pharmaceutical fields because of the wide spreading bio-resources, complex molecular structures and various bioactivities. Bio-producers of cyclopeptides distribute over almost every kingdom from bacteria to plants and animals. Many cyclopeptides contain non-coded amino acids and non-pepditic bonds. Most exciting characteristic of cyclopeptides is a range of interesting bioactivities such as antibiotics gramicidin-S (2), vancomycin (3) and daptomycin (4), immunosuppressive cyclosporin-A (1) and astin-C (8), and anti-tumor aplidine (5), RA-V (6) and RA-VII (7). Compounds 1-4 are being used in clinics; compounds 5-8 are in the stages of clinical trial or as a candidate for drug research. In this review, the progress in chemical and bioactive studies on these important natural bioactive cyclopeptides 1-8 are introduced, mainly including discovery, bioactivity, mechanism, QSAR and synthesis.
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Inmunosupresores , Péptidos Cíclicos , Animales , Antibacterianos/síntesis química , Antibacterianos/química , Antibacterianos/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Antineoplásicos/uso terapéutico , Ciclosporina/química , Ciclosporina/farmacología , Daptomicina/síntesis química , Daptomicina/química , Daptomicina/farmacología , Depsipéptidos/síntesis química , Depsipéptidos/química , Depsipéptidos/uso terapéutico , Gramicidina/síntesis química , Gramicidina/química , Gramicidina/farmacología , Humanos , Terapia de Inmunosupresión , Inmunosupresores/síntesis química , Inmunosupresores/química , Inmunosupresores/farmacología , Estructura Molecular , Neoplasias/tratamiento farmacológico , Péptidos Cíclicos/síntesis química , Péptidos Cíclicos/química , Péptidos Cíclicos/farmacología , Péptidos Cíclicos/uso terapéutico , Relación Estructura-Actividad Cuantitativa , Vancomicina/síntesis química , Vancomicina/química , Vancomicina/farmacologíaRESUMEN
OBJECTIVE: To separate and identify cyclopeptides of tubers of Rubia schumanniana. METHOD: The 70% methanol extracts from tubers of Rubia schumanniana were separated and purified by silica gel, RP-18, Sephedax LH-20 and HPLC. Their structures were identified by spectral analysis. RESULT: Nine cyclopeptides were separated and identified as RA- II (1), RA-V (2), RA-VIII (3), rubiyunnanin C (4), RA-X (5), RY-II (6), RA- I (7), RA-XIII (8) and RA-XIII-OMe (9), respectively. CONCLUSION: All of nine cyclopeptides were separated from R. schumanniana for the first time.
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Medicamentos Herbarios Chinos/química , Péptidos Cíclicos/análisis , Rubia/química , Medicamentos Herbarios Chinos/aislamiento & purificación , Estructura Molecular , Péptidos Cíclicos/aislamiento & purificaciónRESUMEN
The polymerization of α-olefins catalyzed by zirconium metallocene catalyst was systematically studied through experiments and density functional theory (DFT) calculations. Having achieved an agreement between theory and experiment, it was found that the effect of the catalyst ligand on the C[double bond, length as m-dash]C insertion reaction was significantly greater than that on the ß-H elimination reaction. Therefore, the molecular weight of polymers can be increased by improving the activity of the C[double bond, length as m-dash]C insertion. In addition, in comparison with propylene, the chain length of α-olefins can directly affect the stereotacticity of polymerization products, owing to steric hindrance between the polymer chain and monomer.
RESUMEN
OBJECTIVE: Infection is a major cause of death in patients with SLE. This study aimed to explore the infection rate in patients with SLE receiving a low dose of intravenous cyclophosphamide (IV-CYC). METHODS: Clinical parameters of 1022 patients with SLE from 24 hospitals in China were collected. Patients were divided into the short-interval and lower-dose (SILD, 400 mg every 2 weeks) IV-CYC group and the high-dose (HD, 500 mg/m2 of body surface area every month) IV-CYC group. The clinical data and infection rate between the two groups were compared. RESULTS: Compared with HD IV-CYC, the infection rate of the SILD IV-CYC group was significantly lower (13.04% vs 22.27%, p=0.001). Respiratory tract infection (10.28% vs 15.23%, p=0.046) and skin/soft tissue infection (1.78% vs 4.3%, p=0.040) were significantly decreased in the SILD IV-CYC group. Moreover, infections occurred most likely in patients with SLE with leucopenia (OR 2.266, 95% CI 1.322 to 3.887, p=0.003), pulmonary arterial hypertension (OR 2.756, 95% CI 1.249 to 6.080, p=0.012) and >15 mg/day of glucocorticoid (OR 2.220, 95% CI 1.097 to 4.489, p=0.027). CONCLUSIONS: SILD IV-CYC showed a lower frequency of infection events than high-dose IV-CYC in patients with SLE.
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Inmunosupresores , Lupus Eritematoso Sistémico , Humanos , Inmunosupresores/efectos adversos , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/tratamiento farmacológico , Ciclofosfamida/efectos adversos , GlucocorticoidesRESUMEN
Twelve new arborinane-type triterpenoids (1-12) and four new anthraquinones (13-16), together with 50 known compounds, were isolated from the roots of Rubia yunnanensis. The structures of 1-16 were elucidated by spectroscopic data analysis and chemical methods. All compounds were evaluated for their cytotoxic, antibacterial, and antifungal activities. Rubiyunnanol C (5) is the first example of an arborinane-type triterpenoid with a double bond at C-8-C-9.
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Antraquinonas/aislamiento & purificación , Antraquinonas/farmacología , Antiinfecciosos/aislamiento & purificación , Antiinfecciosos/farmacología , Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/farmacología , Medicamentos Herbarios Chinos/aislamiento & purificación , Medicamentos Herbarios Chinos/farmacología , Rubia/química , Triterpenos/aislamiento & purificación , Triterpenos/farmacología , Antraquinonas/química , Antiinfecciosos/química , Antineoplásicos Fitogénicos/química , Candida albicans/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Medicamentos Herbarios Chinos/química , Células HeLa , Humanos , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Raíces de Plantas/química , Staphylococcus aureus/efectos de los fármacos , Relación Estructura-Actividad , Triterpenos/químicaRESUMEN
Class F G protein-coupled receptors are characterized by a large extracellular domain (ECD) in addition to the common transmembrane domain (TMD) with seven α-helixes. For smoothened receptor (SMO), structural studies revealed dissected ECD and TMD, and their integrated assemblies. However, distinct assemblies were reported under different circumstances. Using an unbiased approach based on four series of cross-conjugated bitopic ligands, we explore the relationship between the active status and receptor assembly. Different activity dependency on the linker length for these bitopic ligands corroborates the various occurrences of SMO assembly. These results reveal a rigid "near" assembly for active SMO, which is in contrast to previous results. Conversely, inactive SMO adopts a free ECD, which would be remotely captured at "far" assembly by cholesterol. Altogether, we propose a mechanism of cholesterol flow-caused SMO activation involving an erection of ECD from far to near assembly.
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Hidroxicolesteroles/metabolismo , Receptor Smoothened/metabolismo , Anilidas/síntesis química , Anilidas/metabolismo , Animales , Sitios de Unión , Células HEK293 , Humanos , Hidroxicolesteroles/síntesis química , Ligandos , Ratones , Células 3T3 NIH , Polietilenglicoles/síntesis química , Polietilenglicoles/metabolismo , Dominios Proteicos , Piridinas/síntesis química , Piridinas/metabolismo , Receptor Smoothened/agonistas , Receptor Smoothened/antagonistas & inhibidores , Receptor Smoothened/químicaRESUMEN
Adenosine is an immunosuppressive factor in the tumor microenvironment mainly through activation of the A2A adenosine receptor (A2AR), which is a mechanism hijacked by tumors to escape immune surveillance. Small-molecule A2AR antagonists are being evaluated in clinical trials as immunotherapeutic agents, but their efficacy is limited as standalone therapies. To enhance the antitumor effects of A2AR antagonists, dual-acting compounds incorporating A2AR antagonism and histone deacetylase (HDAC) inhibitory actions were designed and synthesized, based on co-crystal structures of A2AR. Compound 24e (IHCH-3064) exhibited potent binding to A2AR (Ki = 2.2 nM) and selective inhibition of HDAC1 (IC50 = 80.2 nM), with good antiproliferative activity against tumor cell lines in vitro. Intraperitoneal administration of 24e (60 mg/kg, bid) inhibited mouse MC38 tumor growth with a tumor growth inhibition rate of 95.3%. These results showed that dual-acting compounds targeting A2AR and HDAC are potentially immunotherapeutic agents that are worth further exploring.
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Agonistas del Receptor de Adenosina A2/farmacología , Antineoplásicos/farmacología , Diseño de Fármacos , Inhibidores de Histona Desacetilasas/farmacología , Inmunosupresores/farmacología , Receptor de Adenosina A2A/metabolismo , Agonistas del Receptor de Adenosina A2/química , Animales , Antineoplásicos/química , Inhibidores de Histona Desacetilasas/química , Humanos , Terapia de Inmunosupresión , Inmunosupresores/química , Ratones , Prueba de Estudio Conceptual , Relación Estructura-ActividadRESUMEN
Azobenzene-embedded photoswitchable ligands are the widely used chemical tools in photopharmacological studies. Current approaches to azobenzene introduction rely mainly on the isosteric replacement of typical azologable groups. However, atypical scaffolds may offer more opportunities for photoswitch remodeling, which are chemically in an overwhelming majority. Herein, we investigate the rational remodeling of atypical scaffolds for azobenzene introduction, as exemplified in the development of photoswitchable ligands for the cannabinoid receptor 2 (CB2). Based on the analysis of residue-type clusters surrounding the binding pocket, we conclude that among the three representative atypical arms of the CB2 antagonist, AM10257, the adamantyl arm is the most appropriate for azobenzene remodeling. The optimizing spacer length and attachment position revealed AzoLig 9 with excellent thermal bistability, decent photopharmacological switchability between its two configurations, and high subtype selectivity. This structure-guided approach gave new impetus in the extension of new chemical spaces for tool customization for increasingly diversified photo-pharmacological studies and beyond.
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Compuestos Azo/farmacología , Receptor Cannabinoide CB2/metabolismo , Animales , Compuestos Azo/síntesis química , Compuestos Azo/metabolismo , Compuestos Azo/efectos de la radiación , Células CHO , Cricetulus , Diseño de Fármacos , Humanos , Ligandos , Luz , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Receptor Cannabinoide CB2/químicaRESUMEN
Meloyunnanines A-C, three alkaloids with an unprecedented skeleton, were isolated from fruits of Melodinus yunnanensis. The structures featuring a caged-6/6/5/6/5/5 ring system were elucidated by the analysis of comprehensive spectroscopic and X-ray data. Biosynthetically, meloyunnanines A-C were assigned to monoterpenoid quinoline alkaloids (MQAs), derived from monoterpenoid indole alkaloids through oxidation and rearrangement. These compounds together with three known Melodinus MQAs were evaluated for their neurotrophic activity and scandine N4-oxide exhibited significant effect.
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Apocynaceae/química , Monoterpenos/farmacología , Factores de Crecimiento Nervioso/farmacología , Alcaloides de Triptamina Secologanina/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Frutas , Humanos , Estructura Molecular , Monoterpenos/química , Monoterpenos/aislamiento & purificación , Factores de Crecimiento Nervioso/química , Neuritas , Quinolinas/química , Alcaloides de Triptamina Secologanina/química , Alcaloides de Triptamina Secologanina/aislamiento & purificaciónRESUMEN
G-protein-coupled receptors (GPCRs) play important roles in cellular functions. However, their intracellular organization is largely unknown. Through investigation of the cannabinoid receptor 1 (CB1), we discovered periodically repeating clusters of CB1 hotspots within the axons of neurons. We observed these CB1 hotspots interact with the membrane-associated periodic skeleton (MPS) forming a complex crucial in the regulation of CB1 signaling. Furthermore, we found that CB1 hotspot periodicity increased upon CB1 agonist application, and these activated CB1 displayed less dynamic movement compared to non-activated CB1. Our results suggest that CB1 forms periodic hotspots organized by the MPS as a mechanism to increase signaling efficacy upon activation.
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Encéfalo/citología , Imagen Molecular/métodos , Neuronas/metabolismo , Receptor Cannabinoide CB1/metabolismo , Animales , Axones/metabolismo , Encéfalo/metabolismo , Células Cultivadas , Citoesqueleto/metabolismo , Femenino , Recuperación de Fluorescencia tras Fotoblanqueo , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados , Microscopía Fluorescente/métodos , Ratas Sprague-Dawley , Receptor Cannabinoide CB1/análisis , Receptor Cannabinoide CB1/genéticaRESUMEN
[This corrects the article DOI: 10.1021/acscentsci.9b01125.].
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Subtype selectivity and functional bias are vital in current drug discovery for G protein-coupled receptors (GPCRs) as selective and biased ligands are expected to yield drug leads with optimal on-target benefits and minimal side-effects. However, structure-based design and medicinal chemistry exploration remain challenging in part because of highly conserved binding pockets within subfamilies. Herein, we present an affinity mass spectrometry approach for screening herbal extracts to identify active ligands of a GPCR, the 5-HT2C receptor. Using this method, we discovered a naturally occurring aporphine 1857 that displayed strong selectivity for activating 5-HT2C without activating the 5-HT2A or 5-HT2B receptors. Remarkably, this novel ligand exhibited exclusive bias toward G protein signaling for which key residues were identified, and it showed comparable in vivo efficacy for food intake suppression and weight loss as the antiobesity drug, lorcaserin. Our study establishes an efficient approach to discovering novel GPCR ligands by exploring the largely untapped chemical space of natural products.
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The present study describes the preparation of a dodecapeptide YHWYGYTPQNVI (GE11)conjugated liposome bound with polyethylene glycol to enhance the therapeutic effect of resveratrol (RSV) in head and neck cancer cells. The results indicated that (RSV)loaded GE11conjugated liposomes (RSVGL) exhibited a high entrapment efficiency of >95%, with an active drug loading level of 19.5% w/w. Release kinetics revealed that RSV was released in a slow and sustained manner from the RSVGL and RSVloaded liposome (RSVL) nanoparticulate systems. The epidermal growth factor receptor (EGFR)overexpressing squamous cell carcinoma HN cells specifically internalized GE11 surfaceconjugated liposome in a manner that was markedly increased compared with that of the nontargeted carrier. Consistently, RSVGL exhibited a significantly increased cytotoxic effect compared with that of the nontargeted nanoparticles. Notably, RSVGL induced significantly increased proportions of early (~60%) and late (~10%) apoptotic cells in head and neck cancer cell populations. To the best of our knowledge, the application and development of EGFRtargeted peptideconjugated liposome system for RSV delivery has not been studied previously in the treatment of head and neck cancer. In addition, RSVGL exhibited the greatest antitumor efficacy compared with any other group. RSVGL exhibited a 2fold decrease in tumor volume compared with the free RSV and a 3fold decrease in volume compared with the control. Overall, the nanomedicine strategy described in the present study may potentially advance the chemotherapybased treatment of head and neck cancer, with promising applications in other EGFRoverexpressing tumors.
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Péptidos/farmacología , Resveratrol/farmacología , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Secuencia de Aminoácidos , Animales , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Muerte Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Liberación de Fármacos , Femenino , Humanos , Liposomas , Ratones Desnudos , Tamaño de la Partícula , Péptidos/químicaRESUMEN
Human adipose-derived stem cells (hADSCs) are increasingly presumed to be a prospective stem cell source for cell replacement therapy in various degenerative and/or traumatic diseases. The potential of trans-differentiating hADSCs into motor neuron cells indisputably provides an alternative way for spinal cord injury (SCI) treatment. In the present study, a stepwise and efficient hADSC trans-differentiation protocol with retinoic acid (RA), sonic hedgehog (SHH), and neurotrophic factors were developed. With this protocol hADSCs could be converted into electrophysiologically active motoneuron-like cells (hADSC-MNs), which expressed both a cohort of pan neuronal markers and motor neuron specific markers. Moreover, after being primed for neuronal differentiation with RA/SHH, hADSCs were transplanted into SCI mouse model and they survived, migrated, and integrated into injured site and led to partial functional recovery of SCI mice. When ablating the transplanted hADSC-MNs harboring HSV-TK-mCherry overexpression system with antivirial Ganciclovir (GCV), functional relapse was detected by motor-evoked potential (MEP) and BMS assays, implying that transplanted hADSC-MNs participated in rebuilding the neural circuits, which was further confirmed by retrograde neuronal tracing system (WGA). GFP-labeled hADSC-MNs were subjected to whole-cell patch-clamp recording in acute spinal cord slice preparation and both action potentials and synaptic activities were recorded, which further confirmed that those pre-conditioned hADSCs indeed became functionally active neurons in vivo. As well, transplanted hADSC-MNs largely prevented the formation of injury-induced cavities and exerted obvious immune-suppression effect as revealed by preventing astrocyte reactivation and favoring the secretion of a spectrum of anti-inflammatory cytokines and chemokines. Our work suggests that hADSCs can be readily transformed into MNs in vitro, and stay viable in spinal cord of the SCI mouse and exert multi-therapeutic effects by rebuilding the broken circuitry and optimizing the microenvironment through immunosuppression.