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1.
J Agric Food Chem ; 71(40): 14649-14665, 2023 Oct 11.
Artículo en Inglés | MEDLINE | ID: mdl-37755883

RESUMEN

In this study, blueberry (Vaccinium ssp.) anthocyanins (VA) and blackberry (Rubus L.) anthocyanins (RA) were used to investigate the effects on metabolic syndrome (MetS) and the potential mechanisms. Importantly, all of the data presented in this study were obtained from experiments conducted on mice. As a result, VA and RA reduced body weight gain and fat accumulation while improving liver damage, inflammation, glucose, and lipid metabolism induced by a high-fat diet. Moreover, VA and RA regulated the gut microbiota composition, decreasing the pro-obesity and proinflammation bacteria taxa, such as the phylum Actinobacterium and the genera Allobaculum and Bifidobacterium, and increasing those negatively associated with obesity and inflammation, such as the phylum Bacteroidetes and the genera Prevotella and Oscillospira. Additionally, the supplementation with VA and RA reversed the elevated levels of valeric, caproic, and isovaleric acids observed in the high-fat diet (HFD) group, bringing them closer to the levels observed in the Chow group. This reversal indicated that alterations in the composition and abundance of gut microbiota may contribute to the restoration of short-chain fatty acids (SCFAs) levels. Additionally, PICRUSt2 exhibited that cyanamino acid metabolism and betalain biosynthesis might be the major metabolic pathways in the HVA group compared with the HFD group, while in the HRA group, it was the phosphotransferase system. These findings suggest that VA and RA can ameliorate MetS by modulating the gut microbiota and production of SCFAs.

2.
Comput Math Methods Med ; 2022: 5254628, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36388162

RESUMEN

Objective: To study the mechanism of acupuncture on premature ovarian failure (POF) through the apoptosis pathway mediated by Bcl-2/Bax. Methods: POF rats were successfully obtained by cyclophosphamide. They were divided into five groups. After that, acupuncture was performed. The blank group and model group were not treated. The routine acupuncture group was acupuncture at Guanyuan, Sanyinjiao, Zhongji, and Guilai four points. The Neck-seven-acupuncture group was selected from Fengchi, Fengfu, Tianzhu, and Wangu four acupoints; the three-viscera simultaneous treatment group selected Guanyuan, Shenshu, Sanyinjiao, Taichong, and Baihui five points; and the data mining group selected Guanyuan and Sanyinjiao two points for 14 days of treatment. During the treatment, some rats were shed one after another due to the side effects of bone marrow suppression caused by mold-making. After treatment, serum estradiol (E2), follicle forming hormone (FSH), and luteinizing hormone (LH) were detected by radioimmunoassay, Bcl-2 and Bax proteins were analyzed by Western blot method, and Bcl-2 and Bax RNA were analyzed by PCR method. Results: Bcl-2 increased and Bax decreased in rats with premature ovarian failure treated with acupuncture. It shows that acupuncture can affect the secretion of ovarian-related hormones and the expression of apoptosis-related proteins, which is more significant in the conventional acupuncture point group. Conclusion: Acupuncture can inhibit the apoptosis of granulosa cells in ovarian tissue of rats with premature ovarian failure and improve ovarian function. The mechanism of its effect is to promote Bcl-2 gene expression and protein synthesis and inhibit Bax gene expression and protein synthesis. The conventional treatment group works best. This provides an experimental basis for the clinical use of acupuncture to intervene in the treatment of premature ovarian failure.


Asunto(s)
Terapia por Acupuntura , Insuficiencia Ovárica Primaria , Femenino , Humanos , Ratas , Animales , Insuficiencia Ovárica Primaria/terapia , Insuficiencia Ovárica Primaria/metabolismo , Proteína X Asociada a bcl-2/genética , Terapia por Acupuntura/métodos , Puntos de Acupuntura , Proteínas Proto-Oncogénicas c-bcl-2/genética
3.
Chem Biodivers ; 19(9): e202200362, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35924830

RESUMEN

The quality of the root bark of Morus alba L. (SBP) herbs currently circulating in the market is variable. In order to ensure clinical effectiveness, a high-performance liquid chromatography (HPLC) fingerprinting method combined with chemical pattern recognition should be established to control the quality of SBP herbs. The differences of 23 batches of SBP were analyzed by exploratory cluster analysis based on shared fingerprint peak data, and the results indicated that the processing method to remove the cork layer from SBP materials is an important influencing factor on SBP quality. Principal component analysis indicated that SBP samples with the cork layer removed can be clearly distinguished from samples without cork layer removal. The potential chemical markers (kuwanon G, morusin and oxyresveratrol) were screened by partial least squares discriminant analysis. Finally, the contents of the main components were determined, indicating that the processing method of SBP materials can affect content of bioactive ingredients and that cork layer removal leads to a more uniform chemometric profile. The HPLC-based chemometrics approach described here will support the development of quality standards in SBP products.


Asunto(s)
Medicamentos Herbarios Chinos , Morus , Quimiometría , Cromatografía Líquida de Alta Presión/métodos , Medicamentos Herbarios Chinos/química , Morus/química , Corteza de la Planta/química
4.
Small ; 18(21): e2200179, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35396783

RESUMEN

Target therapy for highly heterogeneous cancers represents a major clinical challenge due to the lack of recurrent therapeutic targets identified in these tumors. Herein, the authors report a tumor-customized targeting photothermal therapy (PTT) strategy for highly heterogeneous cancers, by which 2D supramolecular self-assembled nanodiscs are modified with tumor-specific binding peptides identified by phage display techniques. Taking osteosarcoma (OS) as a model heterogeneous cancer, an OS targeting peptide (OTP) is first selected after biopanning and is demonstrated to successfully bind to this heterogeneous cancer cells/tissues. Successful conjugation of OTP to heptamethine cyanine (Cy7)-based 2D nanodiscs Cy7-TCF (2-dicyanomethylene-3-cyano-4,5,5-trimethyl-2,5-dihydrofuran,TCF) enables the 2D nanodiscs to specifically target the heterogeneous tumor. Notably, a single dose injection of this targeted nanodisc (T-ND) not only effectively induces enhanced photothermal tumor ablation under near-infrared light, but also exhibits sevenfold increase of tumor retention time (more than 24 days) compared to generic nanomedicine. Thus, the authors' findings suggest that the combination of phage display-based affinity peptides selection and 2D supramolecular nanodiscs leads to the development of a platform technology for highly heterogeneous cancers precise therapy, offering specific tumor targeting, ultralong tumor retention, and precise PTT.


Asunto(s)
Nanopartículas , Neoplasias , Línea Celular Tumoral , Humanos , Rayos Infrarrojos , Nanomedicina , Nanopartículas/química , Neoplasias/tratamiento farmacológico , Fototerapia , Terapia Fototérmica
5.
Comput Math Methods Med ; 2022: 4295985, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35096130

RESUMEN

OBJECTIVE: Based on resting-state functional magnetic resonance imaging (rs-fMRI), to observe the changes of brain function of bilateral uterine points stimulated by electroacupuncture, so as to provide imaging basis for acupuncture in the treatment of gynecological and reproductive diseases. METHODS: 20 healthy female subjects were selected to stimulate bilateral uterine points (EX-CA1) by electroacupuncture. FMRI data before and after acupuncture were collected. The ReHo values before and after acupuncture were compared by using the analysis method of regional homogeneity (ReHo) of the whole brain, so as to explore the regulatory effect of acupuncture intervention on brain functional activities of healthy subjects. RESULTS: Compared with before acupuncture, the ReHo values of the left precuneus lobe, left central posterior gyrus, calcarine, left lingual gyrus, and cerebellum decreased significantly after acupuncture. CONCLUSION: Electroacupuncture at bilateral uterine points can induce functional activities in brain areas such as the precuneus, cerebellum, posterior central gyrus, talform sulcus, and lingual gyrus. The neural activities in these brain areas may be related to reproductive hormone level, emotional changes, somatic sensation, and visual information. It can clarify the neural mechanism of acupuncture at uterine points in the treatment of reproductive and gynecological diseases to a certain extent.


Asunto(s)
Puntos de Acupuntura , Electroacupuntura/métodos , Imagen por Resonancia Magnética/métodos , Útero/diagnóstico por imagen , Adulto , Encéfalo/fisiología , Mapeo Encefálico , Biología Computacional , Femenino , Neuroimagen Funcional/métodos , Neuroimagen Funcional/estadística & datos numéricos , Enfermedades de los Genitales Femeninos/diagnóstico por imagen , Enfermedades de los Genitales Femeninos/fisiopatología , Voluntarios Sanos , Humanos , Imagen por Resonancia Magnética/estadística & datos numéricos , Útero/fisiología , Adulto Joven
6.
Digital Chinese Medicine ; (4): 59-67, 2022.
Artículo en Inglés | WPRIM | ID: wpr-974084

RESUMEN

@#Objective The resting-state functional magnetic resonance imaging (rs-fMRI) method was used to observe brain activity and its functional connection upon electroacupuncture stimulation at bilateral uterine acupoints (EX-CA1), as well as to investigate the mechanism of acupuncture in the treatment of gynecological diseases. Methods Twenty-two healthy female subjects were stimulated by electroacupuncture at bilateral uterine acupoints; rs-fMRI data of the brain were acquired and standardized. Degree centrality (DC), amplitude of low-frequency fluctuation (ALFF), and regional homogeneity (ReHo) were used to analyze local spontaneous brain activity via acupuncture. An independent component analysis was used to evaluate the functional connectivity of the resting brain networks after acupuncture. Results Analytical results showed that the neural activity intensity of the precuneus lobe, orbitofrontal cortex, lingual gyrus, amygdala, and posterior central gyrus decreased after acupuncture (voxel P < 0.001, cluster P < 0.05). Functional connectivity analysis revealed weakened auditory and right frontal-parietal networks (voxel P < 0.001, cluster P < 0.05), enhanced visual network (voxel P < 0.001, cluster P < 0.05), and synergistic auditory network and hypothalamic-pituitary system. Conclusion Significant differences in neural activity and functional connectivity in specific brain regions were observed after acupuncture intervention at uterine acupoints; the hypothalamic-pituitary system also showed various active states in different brain regions. It is speculated that the effective mechanism of acupuncture at uterine acupoints is related to the regulation of reproductive hormones, emotional changes, and somatic sensations. Therefore, the methods used in this study could clarify the neural mechanism of uterine-point acupuncture in the treatment of gynecological diseases and may serve as a reference for other studies pertaining to acupuncture.

7.
Biomaterials ; 274: 120853, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-33975275

RESUMEN

Tissue damage caused by hyperthermia during photothermal therapy (PTT) has largely limited its clinical applications for implant infection. However, rescue of tissue regeneration by conjugating orthobiologics with PTT has been problematic as they can easily deactivate biologics while eradicating bacteria. Herein, we report an orthobiologics-free strategy to synergistically couple photocatalytic antibacterial with pro-osteogenic capacity via self-assembly of copper sulphide nanoparticle (CuS NP) and reduced graphene oxide (rGO) on implant surface. This strategy not only offers enhanced photothermal effects for bacterial eradiation via near-infrared light (NIR), but also promotes vascularized osseointegration via cooperation of copper ion with rGO. In vitro and in vivo data showed that coupling CuS and rGO synergistically increased antibacterial efficacy of implants by 40 times and successfully destroyed bacterial biofilm upon NIR. Moreover, CuS/rGO decorated surface substantially improved bone marrow stromal cell adhesion, proliferation, as well as subsequent differentiation toward osteoblast. We also revealed that enhanced peri-implant vascularization may be attributed to the sustained release of copper ion from CuS NPs, which further collaborated with rGO to promote vascularized osseointegration. Altogether, this novel orthobiologics-free approach offers a practical alternative to circumvent the intrinsic drawbacks of PTT and endows powerful antibacterial and pro-osteogenic capacities for implant associated infections.


Asunto(s)
Hipertermia Inducida , Nanopartículas , Antibacterianos/farmacología , Cobre , Oseointegración , Fototerapia
8.
Zhongguo Zhen Jiu ; 41(3): 279-82, 2021 Mar 12.
Artículo en Chino | MEDLINE | ID: mdl-33798310

RESUMEN

OBJECTIVE: To observe the influence of regulating menstruation and promoting pregnancy acupuncture therapy on negative emotions in patients with premature ovarian insufficiency (POI). METHODS: A total of 60 patients with POI were randomly divided into an acupuncture group and a western medication group, 30 cases in each group. The acupuncture group was treated with regulating menstruation and promoting pregnancy acupuncture therapy at Baihui (GV 20), Shenting (GV 24), Guanyuan (CV 4), Sanyinjiao (SP 6), Shenshu (BL 23), Ciliao (BL 32), etc. once a day, 5 times a week for 3 months. The western medication group was treated by oral administration of climen. The drug was given 1 tablet a day for 21 days and was stopped for 1 week as a course. The treatment was required 3 consecutive courses. The self-rating anxiety scale (SAS) score, modified Kupperman index (KI) score, agitated and depressive symptom scores in KI and serum level of follicle stimulating hormone (FSH) before and after treatment were compared between the two groups. RESULTS: After treatment, the SAS scores, KI scores and serum levels of FSH in the two groups and the scores of agitated and depressive symptom in the acupuncture group were lower than those before treatment (P<0.05), and the acupuncture group was lower than the western medication group (P<0.05). CONCLUSION: Regulating menstruation and promoting pregnancy acupuncture therapy can effectively improve the negative emotions of patients with POI and reduce serum level of FSH .


Asunto(s)
Terapia por Acupuntura , Insuficiencia Ovárica Primaria , Puntos de Acupuntura , Femenino , Hormona Folículo Estimulante , Humanos , Menstruación , Embarazo , Insuficiencia Ovárica Primaria/terapia
9.
Oxid Med Cell Longev ; 2020: 8965047, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33959213

RESUMEN

Biochanin A (BCA), a dietary isoflavone extracted from red clover and cabbage, has been shown to antagonize hypertension and myocardial ischemia/reperfusion injury. However, very little is known about its role in atherogenesis. The aim of this study was to observe the effects of BCA on atherosclerosis and explore the underlying mechanisms. Our results showed that administration of BCA promoted reverse cholesterol transport (RCT), improved plasma lipid profile, and decreased serum proinflammatory cytokine levels and atherosclerotic lesion area in apoE-/- mice fed a Western diet. In THP-1 macrophage-derived foam cells, treatment with BCA upregulated ATP-binding cassette (ABC) transporter A1 (ABCA1) and ABCG1 expression and facilitated subsequent cholesterol efflux and diminished intracellular cholesterol contents by activating the peroxisome proliferator-activated receptor γ (PPARγ)/liver X receptor α (LXRα) and PPARγ/heme oxygenase 1 (HO-1) pathways. BCA also activated these two signaling pathways to inhibit the secretion of proinflammatory cytokines. Taken together, these findings suggest that BCA is protective against atherosclerosis by inhibiting lipid accumulation and inflammatory response through the PPARγ/LXRα and PPARγ/HO-1 pathways. BCA may be an attractive drug for the prevention and treatment of atherosclerotic cardiovascular disease.


Asunto(s)
Aterosclerosis/sangre , Aterosclerosis/tratamiento farmacológico , Brassica/química , Genisteína/administración & dosificación , Metabolismo de los Lípidos/efectos de los fármacos , Fitoterapia/métodos , Extractos Vegetales/administración & dosificación , Sustancias Protectoras/administración & dosificación , Trifolium/química , Transportador 1 de Casete de Unión a ATP/metabolismo , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 1/metabolismo , Animales , Aterosclerosis/etiología , Colesterol/metabolismo , Citocinas/sangre , Dieta Occidental/efectos adversos , Modelos Animales de Enfermedad , Células Espumosas/efectos de los fármacos , Células Espumosas/metabolismo , Hemo-Oxigenasa 1/metabolismo , Humanos , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Lípidos/sangre , Receptores X del Hígado/metabolismo , Masculino , Ratones , Ratones Noqueados para ApoE , PPAR gamma/metabolismo , Transducción de Señal/efectos de los fármacos , Células THP-1
10.
J Orthop Res ; 37(4): 821-831, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30835895

RESUMEN

A poor vascular supply of the fracture gap is a key factor for the development of atrophic non-unions. Mineral-coated microparticles (MCM) represent a sophisticated carrier system for the delivery of vascular endothelial growth factor (VEGF). Hence, we investigated whether VEGF-loaded MCM improve bone repair in non-unions. For this purpose, we analyzed binding and release kinetics of MCM for VEGF in vitro. Moreover, we applied VEGF-loaded or -unloaded MCM in a murine non-union model in vivo and studied the process of bone healing by means of biomechanical, radiological, histomorphometric, and Western blot techniques. MCM-free non-unions served as controls. The binding efficiency of MCM for VEGF was 46 ± 3% and the release profile revealed an initial minor burst release followed by a sustained release over a 50-day study period, thus, mimicking the physiological expression profile of VEGF during bone healing. In vivo, bone defects treated with VEGF-loaded MCM exhibited a higher bending stiffness, a higher fraction of bone volume/tissue volume and a larger callus area on days 14 and 70 when compared to the other groups. Western blot analyses on day 14 revealed a higher expression of VEGF, erythropoietin (EPO), and runt-related transcription factor 2, but not of EPO-receptor in bone defects treated with VEGF-loaded MCM. These findings demonstrate that the use of MCM for VEGF delivery shows great potential due to the ability to maintain protein stability and functionality in vivo. Moreover, the application of VEGF-loaded MCM represent a promising strategy for the treatment of non-unions. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.


Asunto(s)
Portadores de Fármacos , Curación de Fractura/efectos de los fármacos , Fracturas no Consolidadas/tratamiento farmacológico , Factor A de Crecimiento Endotelial Vascular/administración & dosificación , Animales , Subunidad alfa 1 del Factor de Unión al Sitio Principal/metabolismo , Evaluación Preclínica de Medicamentos , Eritropoyetina/metabolismo , Fracturas no Consolidadas/metabolismo , Ratones
11.
Zhen Ci Yan Jiu ; 43(7): 440-4, 2018 Jul 25.
Artículo en Chino | MEDLINE | ID: mdl-30094981

RESUMEN

OBJECTIVE: To observe the effect of liver-soothing and mental-activity-regulating (LSMAR) needling on the expression of receptor activity-modifying protein 1 (RAMP 1, receptor of calcitonin gene-related peptide), 5-hydroxytryptamine 1 D receptor(5-HT 1 DR) in the spinal trigeminal nucleus (STN) and midbrain in migraine rats, so as to explore its underlying mechanism in relieving migraine. METHODS: A total of 40 male Wistar rats were randomly divided into control, model, LSMAR and conventional needling groups (n=10 rats in each). The migraine model was established by subcutaneous injection of nitroglycerin at the posterior neck. LSMAR was applied to "Baihui" (GV 20), bilateral "Fengchi" (GB 20), "Neiguan" (PC 6) and "Taichong" (LR 3) in the LSMAR group and conventional needling was applied to "Baihui" (GV 20) and bilateral "Fengchi" (GB 20) in the conventional acupuncture group for 30 min, once a day for 8 days before modeling. The expression levels of RAMP 1 and 5-HT 1 DR proteins and mRNAs in the STN and mesencephalon were detected by real-time fluorescent quantitative PCR and Western blot, separately. RESULTS: Compared with the control group, the expression levels of RAMP 1 protein and mRNA in STN and mesencephalon were significantly increased (P<0.05) and those of 5-HT 1 DR protein and mRNA considerably decreased (P<0.05) in the model group. After the acupuncture treatment, the increased levels of RAMP 1 protein and mRNA and the decreased levels of 5-HT 1 DR protein and mRNA in the STN and midbrain were obviously reversed in the LSMAR and conventional needling groups relevant to the model group (P<0.05). The effect of LSMAR needling was significantly superior to that of conventional needling in down-regulating the expression levels of RAMP 1 mRNA and protein in the STN and mesencephalon (P<0.05) and in up-regulating the expression levels of 5-HT 1 DR mRNA and protein in the two brain regions (P<0.05). CONCLUSION: Manual acupuncture stimulation of GV 20, GB 20, etc. can inhibit the expression of RAMP 1 protein and mRNA in the STN and midbrain, and up-regulate the expression of 5-HT 1 DR in the two brain regions of migraine rats, which may be related to its effect in relieving migraine.


Asunto(s)
Terapia por Acupuntura , Trastornos Migrañosos , Puntos de Acupuntura , Animales , Masculino , Trastornos Migrañosos/terapia , Ratas , Ratas Wistar , Proteína 1 Modificadora de la Actividad de Receptores , Serotonina
12.
Zhen Ci Yan Jiu ; 43(6): 375-9, 2018 Jun 25.
Artículo en Chino | MEDLINE | ID: mdl-30091544

RESUMEN

OBJECTIVE: To observe the effect of liver-soothing and mental-activity-regulating (LSMAR) needling on behavior reactions and contents of serum calcitonin gene-related peptide (CGRP), substance P (SP), interleukin-1 ß (IL-1 ß) and tumor necrosis factor-α (TNF-α) in migraine rats, so as to explore its mechanism underlying relief of migraine. METHODS: Thirty-two male Wistar rats were randomly divided into control, model, LSMAR needling and conventional needling groups (n=8 rats in each). The migraine model was established by hypodermic injection of glyceryl trinitrate (5 mg/kg) at the napex. Acupuncture preconditioning was conducted once daily for 8 days before modeling. Acupuncture needles were inserted into "Baihui" (GV 20), and bilateral "Fengchi" (GB 20), "Neiguan" (PC 6) and "Taichong" (LR 3), manipulated for a while and retained for 30 min. The rats' behavioral changes (times of head scratching, tail-biting, cage-crawling, and to- and fro-movement in 30 min) were scored (one symptom = one point) before modeling, after modeling, and after intervention. The concentrations of CGRP, SP, IL-1 ß, TNF-α in serum were assayed by enzyme-linked immunosorbent assay (ELISA). RESULTS: After modeling, the behavioral scores were significantly increased in the migraine model rats relevant to the control group (P<0.05). Whereas after the treatment, the behavior scores were considerably decreased during 60-90 min and 120-150 min of the measuring period in both LSMAR and conventional needling groups compared with the model group (P<0.05). The concentrations of CGRP, SP, IL-1 ß and TNF-α were significantly higher in the model group than in the control group (P<0.05), and notably lower in both LSMAR and conventional needling groups than in the model group (P<0.05). The therapeutic effect of LSMAR was markedly superior to that of conventional needling in down-regulating the concentrations of CGRP, SP, IL-1 ß and TNF-α (P<0.05). CONCLUSION: Acupuncture preconditioning can effectively relieve pain in migraine rats possibly by decreasing the concentrations of CGRP, SP, IL-1 ß and TNF-α in the peripheral blood, and the therapeutic effect of LSMAR is evidently superior to that of conventional needling.


Asunto(s)
Terapia por Acupuntura , Trastornos Migrañosos , Animales , Calcitonina , Péptido Relacionado con Gen de Calcitonina , Interleucina-1beta , Masculino , Ratas , Ratas Sprague-Dawley , Ratas Wistar , Sustancia P , Factor de Necrosis Tumoral alfa
13.
Biomaterials ; 161: 240-255, 2018 04.
Artículo en Inglés | MEDLINE | ID: mdl-29421560

RESUMEN

High-density mesenchymal stem cell (MSC) aggregates can be guided to form bone-like tissue via endochondral ossification in vitro when culture media is supplemented with proteins, such as growth factors (GFs), to first guide the formation of a cartilage template, followed by culture with hypertrophic factors. Recent reports have recapitulated these results through the controlled spatiotemporal delivery of chondrogenic transforming growth factor-ß1 (TGF-ß1) and chondrogenic and osteogenic bone morphogenetic protein-2 (BMP-2) from microparticles embedded within human MSC aggregates to avoid diffusion limitations and the lengthy, costly in vitro culture necessary with repeat exogenous supplementation. However, since GFs have limited stability, localized gene delivery is a promising alternative to the use of proteins. Here, mineral-coated hydroxyapatite microparticles (MCM) capable of localized delivery of Lipofectamine-plasmid DNA (pDNA) nanocomplexes encoding for TGF-ß1 (pTGF-ß1) and BMP-2 (pBMP-2) were incorporated, alone or in combination, within MSC aggregates from three healthy porcine donors to induce sustained production of these transgenes. Three donor populations were investigated in this work due to the noted MSC donor-to-donor variability in differentiation capacity documented in the literature. Delivery of pBMP-2 within Donor 1 aggregates promoted chondrogenesis at week 2, followed by an enhanced osteogenic phenotype at week 4. Donor 2 and 3 aggregates did not promote robust glycosaminoglycan (GAG) production at week 2, but by week 4, Donor 2 aggregates with pTGF-ß1/pBMP-2 and Donor 3 aggregates with both unloaded MCM and pBMP-2 enhanced osteogenesis compared to controls. These results demonstrate the ability to promote osteogenesis in stem cell aggregates through controlled, non-viral gene delivery within the cell masses. These findings also indicate the need to screen donor MSC regenerative potential in response to gene transfer prior to clinical application. Taken together, this work demonstrates a promising gene therapy approach to control stem cell fate in biomimetic 3D condensations for treatment of bone defects.


Asunto(s)
Ingeniería de Tejidos/métodos , Animales , Proteína Morfogenética Ósea 2/administración & dosificación , Proteína Morfogenética Ósea 2/farmacología , Huesos/citología , Células Cultivadas , Condrogénesis/efectos de los fármacos , Durapatita/química , Técnicas de Transferencia de Gen , Glicosaminoglicanos , Humanos , Células Madre Mesenquimatosas/citología , Porcinos , Factor de Crecimiento Transformador beta1/administración & dosificación , Factor de Crecimiento Transformador beta1/farmacología
14.
Stem Cells Transl Med ; 5(2): 206-17, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26702127

RESUMEN

Bone tissue engineering via endochondral ossification has been explored by chondrogenically priming cells using soluble mediators for at least 3 weeks to produce a hypertrophic cartilage template. Although recapitulation of endochondral ossification has been achieved, long-term in vitro culture is required for priming cells through repeated supplementation of inductive factors in the media. To address this challenge, a microparticle-based growth factor delivery system was engineered to drive endochondral ossification within human bone marrow-derived mesenchymal stem cell (hMSC) aggregates. Sequential exogenous presentation of soluble transforming growth factor-ß1 (TGF-ß1) and bone morphogenetic protein-2 (BMP-2) at various defined time courses resulted in varying degrees of chondrogenesis and osteogenesis as demonstrated by glycosaminoglycan and calcium content. The time course that best induced endochondral ossification was used to guide the development of the microparticle-based controlled delivery system for TGF-ß1 and BMP-2. Gelatin microparticles capable of relatively rapid release of TGF-ß1 and mineral-coated hydroxyapatite microparticles permitting more sustained release of BMP-2 were then incorporated within hMSC aggregates and cultured for 5 weeks following the predetermined time course for sequential presentation of bioactive signals. Compared with cell-only aggregates treated with exogenous growth factors, aggregates with incorporated TGF-ß1- and BMP-2-loaded microparticles exhibited enhanced chondrogenesis and alkaline phosphatase activity at week 2 and a greater degree of mineralization by week 5. Staining for types I and II collagen, osteopontin, and osteocalcin revealed the presence of cartilage and bone. This microparticle-incorporated system has potential as a readily implantable therapy for healing bone defects without the need for long-term in vitro chondrogenic priming. Significance: This study demonstrates the regulation of chondrogenesis and osteogenesis with regard to endochondral bone formation in high-density stem cell systems through the controlled presentation of inductive factors from incorporated microparticles. This work lays the foundation for a rapidly implantable tissue engineering system that promotes bone repair via endochondral ossification, a pathway that can delay the need for a functional vascular network and has an intrinsic ability to promote angiogenesis. The modular nature of this system lends well to using different cell types and/or growth factors to induce endochondral bone formation, as well as the production of other tissue types.


Asunto(s)
Células de la Médula Ósea/efectos de los fármacos , Proteína Morfogenética Ósea 2/farmacología , Condrogénesis/efectos de los fármacos , Células Madre Mesenquimatosas/efectos de los fármacos , Osteogénesis/efectos de los fármacos , Factor de Crecimiento Transformador beta1/farmacología , Fosfatasa Alcalina/genética , Fosfatasa Alcalina/metabolismo , Biomarcadores/metabolismo , Células de la Médula Ósea/citología , Células de la Médula Ósea/metabolismo , Proteína Morfogenética Ósea 2/metabolismo , Calcificación Fisiológica/efectos de los fármacos , Calcificación Fisiológica/genética , Calcio/metabolismo , Agregación Celular , Condrogénesis/genética , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Colágeno Tipo II/genética , Colágeno Tipo II/metabolismo , Preparaciones de Acción Retardada , Composición de Medicamentos , Durapatita/química , Gelatina/química , Expresión Génica , Glicosaminoglicanos/metabolismo , Humanos , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/metabolismo , Osteocalcina/genética , Osteocalcina/metabolismo , Osteogénesis/genética , Osteopontina/genética , Osteopontina/metabolismo , Cultivo Primario de Células , Ingeniería de Tejidos/métodos , Factor de Crecimiento Transformador beta1/metabolismo
15.
ACS Biomater Sci Eng ; 2(1): 30-42, 2016 Jan 11.
Artículo en Inglés | MEDLINE | ID: mdl-33418642

RESUMEN

Since hydroxyapatite and bone morphogenetic protein-2 (BMP-2) can regulate chondrogenesis and osteogenesis, their individual and combined effects on endochondral ossification within human bone marrow-derived stem cell (hMSC) aggregates were investigated. Hydroxyapatite was presented in the form of mineral-coated hydroxyapatite microparticles (MCM) capable of controlled BMP-2 delivery. Aggregates were treated with varied BMP-2 concentrations supplemented in the media and loaded onto MCM to examine the influence of BMP-2 amount and spatial presentation on regulating chondrogenesis and osteogenesis. MCM alone induced GAG and type II collagen production by week 5 for two of three donors, and BMP-2 may have accelerated MCM-induced chondrogenesis. ALP activity and calcium content of cells-only aggregates suggest that the BMP-2-induced osteogenic response may be concentration-dependent. Treatment with MCM and BMP-2 resulted in chondrogenesis as early as week 2, which may have promoted additional mineralization by week 5, suggesting the induction of endochondral ossification. Released BMP-2 had similar if not higher levels of bioactivity compared to that of exogenous BMP-2 with regard to chondrogenesis and osteogenesis. In addition to providing localized and sustained BMP-2 delivery, MCM incorporation within aggregates yields a self-sustaining system that may be injected or implanted more rapidly to heal bone defects through endochondral ossification without extended in vitro culture.

16.
Zhongguo Zhen Jiu ; 34(10): 1037-9, 2014 Oct.
Artículo en Chino | MEDLINE | ID: mdl-25543447

RESUMEN

OBJECTIVE: To explore the correlation between hand and face-mouth, so as to provide nerve reflex basis for the theory "Hegu (LI 4) regulates face and mouth". METHODS: Seven hundred and sixty-three participants who met the inclusive criteria were divided into different age groups. The skin around participants' thenar eminence was gently scraped to be observed whether there was an involuntary movement around the face or mouth, which was palmomental reflex. The results of palmomental reflex were recorded. RESULTS: The total occurrence rate of palmomental reflex was 46.26%. For those who were 0 to 1 years old, the palmomental reflex was all positive; for those who were 21 to 36 years old, the positive rate was 20.45%, which was the lowest; for those who were 65 to 85 years old, more than half of them were positive. The majority of those who were 0 to 2 years old were bilateral positive palmomental reflex, while the majority of those who were 65 to 85 years old were unilateral positive palmomental reflex. CONCLUSION: There is a certain connection between hand and face-mouth. The occurrence rate of palmomental reflex changes from high to low over age increasing, and then changes from low to high with the aging, presenting a "high-low-high" U-shaped curve, which is possible related to the growth and recession of nervous system.


Asunto(s)
Puntos de Acupuntura , Terapia por Acupuntura , Cara/fisiopatología , Mano/fisiopatología , Boca/fisiopatología , Reflejo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Adulto Joven
17.
Chemosphere ; 101: 41-8, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24296029

RESUMEN

P recovery from swine wastewater has become a great concern as a result of the high demand for P resources and its potential eutrophication effects on water ecosystems. The method of magnesium ammonium phosphate (MAP) crystallization was used to recover P from simulated swine wastewater, and the effects of three organic acids (citric acid, succinic acid and acetic acid) on P removal efficiency and rate at different pH values were investigated. The results indicated that the P removal efficiency was worst affected by citric acid in the optimal pH range of 9.0-10.5, followed by succinic acid and acetic acid, and the influencing extent of organic acids decreased with the increasing pH value. Due to the complexation between organic acid and Mg(2+)/NH4(+), all of three organic acids could inhibit the P removal rate at the beginning of the reaction, which showed positive correlation between the inhibition effects and the concentration of organic acids. The high concentration of citric acid could completely suppress the MAP crystallization reaction. Moreover, citric acid and succinic acid brought obvious effects on the morphology of the crystallized products. The experimental results also demonstrated that MAP crystals could be obtained in the presence of different kinds and concentrations of organic acids.


Asunto(s)
Ácidos Acíclicos/química , Compuestos de Magnesio/síntesis química , Fosfatos/síntesis química , Fósforo/aislamiento & purificación , Aguas Residuales/química , Animales , Cristalización , Magnesio/química , Estruvita , Porcinos
18.
Zhen Ci Yan Jiu ; 36(5): 388-91, 2011 Oct.
Artículo en Chino | MEDLINE | ID: mdl-22073895

RESUMEN

It has been well documented in Chinese acupuncture medicine that "Hegu (LI 4) is indicated for orofacial problems". In the present paper, the authors analyze their correlation from the learning of modern medicine and results of recent experimental studies instead of traditional meridian theory of acupuncturology. The afferent nerve fibers from the LI 4 region and the orofacial part ascend to the spinal cord, nucleus of solitary tract, reticular formation, thalamus and the cerebral cortex, respectively, and overlap in the thalamus, cerebral cortex, etc. Under the circumstances, the interaction and functional integration of the afferent signals from LI 4 acupoint and the orofacial region may occur in the central nervous system. In addition, many relevant neuroactive substances (for example, serotonin, substance P, enkephalin, y-aminobutyric acid, glycine, calcitonin gene-related peptide, etc.) released from the sensory and motor neurons in the corresponding cerebral regions may constitute part of the substantial basis of that "Hegu (LI 4) is indicated for many orofacial disorders".


Asunto(s)
Puntos de Acupuntura , Terapia por Acupuntura , Enfermedades del Nervio Facial/terapia , Animales , Enfermedades del Nervio Facial/fisiopatología , Humanos
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