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1.
Exp Cell Res ; 422(1): 113440, 2023 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-36481206

RESUMEN

The limited cardiomyocyte proliferation is insufficient for repair of the myocardium. Therefore, activating cardiomyocyte proliferation might be a reasonable option for myocardial regeneration. Here, we investigated effect of retinoic acid (RA) on inducing adult cardiomyocyte proliferation and assessed efficacy of self-assembling peptide (SAP)-released RA in activating regeneration of the infarcted myocardium. Effect of RA on inducing cardiomyocyte proliferation was examined with the isolated cardiomyocytes. Expression of the cell cycle-associated genes and paracrine factors in the infarcted myocardium was examined at one week after treatment with SAP-carried RA. Cardiomyocyte proliferation, myocardial regeneration and improvement of cardiac function were assessed at four weeks after treatment. In the adult rat myocardium, expression of RA synthetase gene Raldh2 and RA concentration were decreased significantly. After treatment with RA, the proliferated cardiomyocytes were increased. The formulated SAP could sustainedly release RA. After treatment with SAP-carried RA, expression of the pro-proliferative genes in cell cycle and paracrine factors in the infarcted myocardium were up-regulated. Myocardial regeneration was enhanced, and cardiac function was improved significantly. These results demonstrate that RA can induce adult cardiomyocytes to proliferate effectively. The sustained release of RA with SAP is a promise strategy to enhance repair of the infarcted myocardium.


Asunto(s)
Infarto del Miocardio , Miocitos Cardíacos , Ratas , Animales , Miocitos Cardíacos/metabolismo , Infarto del Miocardio/metabolismo , Tretinoina/farmacología , Tretinoina/metabolismo , Miocardio/metabolismo , Péptidos/farmacología , Péptidos/metabolismo , Proliferación Celular
2.
Lasers Med Sci ; 38(1): 223, 2023 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-37758965

RESUMEN

The choice between radiotherapy (RT) and CO2 laser surgery (CO2-LS) for early glottic cancer remains controversial. We systematically examined electronic databases in order to identify prospective trials comparing patients who had undergone CO2-LS or RT to treat early glottic cancer. Eleven studies involving 1053 patients were included. In the selected literature, the parameter setting of CO2 laser equipment can be summarized as wavelength 10.6 µm, superpulsed mode, continuous setting, power tailored on target structures (1-3 W for subtle resections and 4-15 W for cutting a larger tumor), and approximately 2080-3900 W/cm2 of laser energy. Using RevMan 5.3, we estimated pooled odds ratios (ORs) for dichotomous variables and pooled mean differences (MDs) for continuous variables, along with associated 95% confidence intervals (CIs). The heterogeneity in the treatment variables was measured using Higgins' inconsistency test and expressed as I2 values. The continuous variables were then depicted as histograms developed using PlotDigitizer 2.6.8. Compared to patients treated with CO2-LS, those treated with RT had better jitter (MD 1.27%, 95% CI 1.21 ~ 1.32, P < 0.001), and high scores on the "Grade (MD 6.54, 95% CI 5.31 ~ 7.76, P < 0.001), Breathiness (MD 9.08, 95% CI 4.02 ~ 14.13, P < 0.001), Asthenia (MD 2.13, 95% CI 0.29 ~ 3.98, P = 0.02), and Strain (MD 3.32, 95% CI 0.57 ~ 6.07, P = 0.02)" scale. Patients treated with CO2-LS had worse local control rates (OR 3.14, 95% CI 1.52 ~ 6.48, P = 0.002) while lower incidence of second primary tumor (OR 0.30, 95% CI 0.15 ~ 0.61, P < 0.001). It is hoped that retrospective analysis can provide suggestions for early glottis patients to choose personalized treatment.


Asunto(s)
Neoplasias Laríngeas , Terapia por Láser , Neoplasias de la Lengua , Humanos , Dióxido de Carbono , Resultado del Tratamiento , Estudios Retrospectivos , Microcirugia , Neoplasias Laríngeas/radioterapia , Neoplasias Laríngeas/cirugía , Neoplasias Laríngeas/patología , Estudios Prospectivos , Terapia por Láser/efectos adversos , Glotis/cirugía , Glotis/patología , Neoplasias de la Lengua/patología
3.
Chem Biodivers ; 20(3): e202201237, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36740572

RESUMEN

Artemisia annua L. is a Chinese medicinal herb, but the origin of its pharmacological properties, including its anti-inflammatory activity, remain unknown. In this study, five new monoterpene glycosides (1-5) and two new sesquiterpene glycosides (6 and 7) were isolated from the aqueous extract of the aerial parts of A. annua. The structures of these glycosides were determined using high-resolution electrospray ionization mass spectrometry, nuclear magnetic resonance spectroscopy, electronic circular dichroism calculations, and chemical hydrolysis methods. The anti-inflammatory activities of the isolated compounds were evaluated by down-regulating interleukin-6 (IL-6) in lipopolysaccharide-stimulated RAW 264.7 macrophages. Notably, all the new compounds significantly inhibited the expression of IL-6 in a dose-dependent manner.


Asunto(s)
Artemisia annua , Artemisia , Sesquiterpenos , Artemisia annua/química , Glicósidos/farmacología , Monoterpenos/farmacología , Interleucina-6 , Antiinflamatorios/farmacología , Antiinflamatorios/química , Agua , Sesquiterpenos/farmacología , Artemisia/química
4.
Zhongguo Zhong Yao Za Zhi ; 48(15): 4147-4155, 2023 Aug.
Artículo en Zh | MEDLINE | ID: mdl-37802783

RESUMEN

Based on the androgen receptor(AR)/mammalian target of rapamycin(mTOR)signaling pathway, the effects of Xihuang Pills-medicated serum on the proliferation and apoptosis of prostate cancer LNCaP cells were investigated. The drug-containing serum of SD rats was prepared by intragastric administration of Xihuang Pills suspension. The effects of low-, medium-, and high-dose Xihuang Pills-containing serum on the in vitro proliferation of LNCaP cells were detected by cell counting kit-8(CCK-8). Flow cytometry was used to detect the apoptosis level of LNCaP cells after intervention with different concentrations of Xihuang Pills. Protein expression of cleaved cysteinyl aspartate-specific proteinase caspase-3(cleaved caspase-3), B-cell lymphoma-2(Bcl-2), and AR as well as the phosphorylation level of mTOR protein were detected by Western blot. The results showed that compared with the blank serum, the drug-medicated serum could blunt the activity of LNCaP cells. Low-, medium-, and high-dose Xihuang Pills-containing serum could significantly increase the cell apoptosis rate, increase the expression of cleaved caspase-3 protein, decrease the expression of Bcl-2 protein, reduce the expression of AR protein, and down-regulate the level of phosphorylated mTOR(p-mTOR). To study the effect of Xihuang Pills on the growth of LNCaP cells in vivo, different doses of Xihuang Pills were used to intervene in the subcutaneous graft model in nude mice inoculated with LNCaP cells. The expression levels of AR, mTOR, p-mTOR, Bcl-2, and cleaved caspase-3 were detected by Western blot. The results showed that the volumes of subcutaneous graft tumor in the low-dose, medium-dose, and high-dose Xihuang Pills groups significantly decreased compared with that in the model group. The weight of subcutaneous transplanted tumor in each group with drug intervention was significantly lower than that in the model group. Compared with the model group, the low-dose, medium-dose, and high-dose Xihuang Pills groups showed increased cleaved caspase-3 protein expression, decreased Bcl-2 and AR protein expression, and reduced p-mTOR protein expression. Further experiments showed that AR agonist R1881 could block the anti-proliferation and pro-apoptotic effects of Xihuang Pills. The mechanism of Xihuang Pills against prostate cancer is related to the inhibition of the AR/mTOR signaling pathway, inhibition of LNCaP cell proliferation, and induction of apoptosis in cancer cells.


Asunto(s)
Neoplasias de la Próstata , Transducción de Señal , Humanos , Masculino , Ratones , Ratas , Animales , Caspasa 3/genética , Caspasa 3/metabolismo , Ratones Desnudos , Línea Celular Tumoral , Ratas Sprague-Dawley , Serina-Treonina Quinasas TOR/genética , Serina-Treonina Quinasas TOR/metabolismo , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/patología , Proliferación Celular , Apoptosis , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Mamíferos/metabolismo
5.
Zhongguo Dang Dai Er Ke Za Zhi ; 25(7): 726-731, 2023 Jul 15.
Artículo en Zh | MEDLINE | ID: mdl-37529955

RESUMEN

OBJECTIVES: To study the genetic characteristics, clinical characteristics, and prognosis of children with primary dilated cardiomyopathy (DCM). METHODS: A retrospective analysis was performed on the medical data of 44 children who were diagnosed with DCM in Hebei Children's Hospital from July 2018 to February 2023. According to the genetic testing results, they were divided into two groups: gene mutation-positive group (n=17) and gene mutation-negative group (n=27). The two groups were compared in terms of clinical data at initial diagnosis and follow-up data. RESULTS: Among the 44 children with DCM, there were 21 boys (48%) and 23 girls (52%). Respiratory symptoms including cough and shortness of breath were the most common symptom at initial diagnosis (34%, 15/44). The detection rate of gene mutations was 39% (17/44). There were no significant differences between the two groups in clinical characteristics, proportion of children with cardiac function grade Ⅲ or Ⅳ, brain natriuretic peptide levels, left ventricular ejection fraction, and left ventricular fractional shortening at initial diagnosis (P>0.05). The median follow-up time was 23 months, and 9 children (20%) died, including 8 children from the gene mutation-positive group, among whom 3 had TTN gene mutation, 2 had LMNA gene mutation, 2 had TAZ gene mutation, and 1 had ATAD3A gene mutation. The gene mutation-positive group had a significantly higher mortality rate than the gene mutation-negative group (P<0.05). CONCLUSIONS: There is no correlation between the severity of DCM at initial diagnosis and gene mutations in children. However, children with gene mutations may have a poorer prognosis.


Asunto(s)
Cardiomiopatía Dilatada , Función Ventricular Izquierda , Masculino , Femenino , Humanos , Niño , Volumen Sistólico , Estudios Retrospectivos , Fenotipo , Cardiomiopatía Dilatada/genética , Cardiomiopatía Dilatada/diagnóstico , Mutación , ATPasas Asociadas con Actividades Celulares Diversas/genética , Proteínas de la Membrana/genética , Proteínas Mitocondriales/genética
6.
J Mol Cell Cardiol ; 167: 40-51, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35314145

RESUMEN

RATIONALE: Mineralocorticoid receptor (MR) antagonists have been clinically used to treat heart failure. However, the underlying cellular and molecular mechanisms remain incompletely understood. METHODS AND RESULTS: Using osteoblast MR knockout (MRobko) mouse in combination with myocardial infarction (MI) model, we demonstrated that MR deficiency in osteoblasts significantly improved cardiac function, promoted myocardial healing, as well as attenuated cardiac hypertrophy, fibrosis and inflammatory response after MI. Gene expression profiling using RNA sequencing revealed suppressed expression of osteocalcin (OCN) in calvaria from MRobko mice compared to littermate control (MRfl/fl) mice with or without MI. Plasma levels of undercarboxylated OCN (ucOCN) were also markedly decreased in MRobko mice compared to MRfl/fl mice. Administration of ucOCN abolished the protective effects of osteoblast MR deficiency on infarcted hearts. Mechanistically, ucOCN treatment promoted proliferation and inflammatory cytokine secretion in macrophages. Spironolactone, an MR antagonist, significantly inhibited the expression and secretion of OCN in post-MI mice. More importantly, spironolactone decreased plasma levels of ucOCN and inflammatory cytokines in heart failure patients. CONCLUSIONS: MR deficiency in osteoblasts alleviates pathological ventricular remodeling after MI, likely through its regulation on OCN. Spironolactone may work through osteoblast MR/OCN axis to exert its therapeutic effects on pathological ventricular remodeling and heart failure in mice and human patients.


Asunto(s)
Insuficiencia Cardíaca , Infarto del Miocardio , Animales , Humanos , Ratones , Antagonistas de Receptores de Mineralocorticoides/farmacología , Infarto del Miocardio/patología , Osteoblastos/metabolismo , Espironolactona , Remodelación Ventricular
7.
Immunology ; 167(1): 94-104, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35751882

RESUMEN

Mineralocorticoid receptor (MR) is a classic nuclear receptor and an effective drug target in the cardiovascular system. The function of MR in immune cells such as macrophages and T cells has been increasingly appreciated. The aim of this study was to investigate the function of Treg MR in the process of inflammatory bowel disease (IBD). We treated Treg MR-deficient (MRflox/flox Foxp3YFP-Cre , KO) mice and control (Foxp3YFP-Cre , WT) mice with dextran sodium sulphate (DSS) to induce colitis and found that the severity of DSS-induced colitis was markedly alleviated in Treg MR-deficient mice, accompanied by reduced production of inflammatory cytokines, and relieved infiltration of monocytes, neutrophils and interferon γ+ T cells in colon lamina propria. Faecal microbiota of mice with colitis was analysed by 16S rRNA gene sequencing and the composition of gut microbiota was vastly changed in Treg MR-deficient mice. Furthermore, depletion of gut microbiota by antibiotics abolished the protective effects of Treg MR deficiency and resulted in similar severity of DSS-induced colitis in WT and KO mice. Faecal microbiota transplantation from KO mice attenuated DSS-induced colitis characterized by alleviated inflammatory infiltration compared to that from WT mice. Hence, our study demonstrates that Treg MR deficiency protects against DSS-induced colitis by attenuation of colonic inflammatory infiltration. Gut microbiota is both sufficient and necessary for Treg MR deficiency to exert the beneficial effects.


Asunto(s)
Colitis , Microbioma Gastrointestinal , Animales , Colitis/inducido químicamente , Colitis/terapia , Colon , Sulfato de Dextran , Modelos Animales de Enfermedad , Factores de Transcripción Forkhead/genética , Ratones , Ratones Endogámicos C57BL , ARN Ribosómico 16S/genética , Receptores de Mineralocorticoides/genética , Linfocitos T Reguladores
8.
Lab Invest ; 102(9): 919-934, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35562411

RESUMEN

Nasopharyngeal carcinoma (NPC), which is marked by a distinct distribution, is a common subtype of epithelial carcinoma arising from the nasopharyngeal mucosal lining. SRGN acts as an important and poor prognostic factor of NPC through multiple different mechanisms. However, the biological role and mechanism of SRGN in NPC remain unknown. Expression levels of miR-148a-5p, CREB1, FoxO1, and SRGN in NPC tissues and cell lines were tested by qRT-PCR or/and Western blot. The impacts of miR-148a-5p, CREB1, FoxO1, and SRGN on NPC cell viability, proliferation, migration, and invasion were estimated in vitro by CCK-8, colony formation, wound healing and Transwell experiments, and in vivo by a xenograft tumor model. JASPAR analysis was used to predict the binding activity of Foxo1 (CREB1) with the miR-148a-5p (SRGN) promoter, and the interaction was validated by EMSA and ChIP assays. The miR-148a-5p-CREB1 interaction was validated by a dual-luciferase reporter and RIP assays. CREB1 and SRGN were increased while miR-148a-5p was decreased in NPC. Silencing of SRGN and CREB1, as well as miR-148a-5p overexpression, repressed NPC tumor progression in vitro and in vivo. CREB1 promoted SRGN expression in NPC by targeting the promoter area of SRGN. Silencing of FoxO1 facilitated NPC tumor progression, while silencing of STAT3 repressed NPC tumor progression. FoxO1 bound to and regulated miR-148a-5p in NPC, and miR-148a-5p targeted CREB1. Additionally, FoxO1 knockdown abolished the downregulation of CREB1 and SRGN induced by STAT3 silencing. Our results suggest that STAT3 regulates SRGN and promotes the growth and metastasis of NPC through the FoxO1-miR-148a-5p-CREB1 axis.


Asunto(s)
MicroARNs , Neoplasias Nasofaríngeas , Proteoglicanos/metabolismo , Proteínas de Transporte Vesicular/metabolismo , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Proteína de Unión a Elemento de Respuesta al AMP Cíclico , Proteína Forkhead Box O1 , Regulación Neoplásica de la Expresión Génica , Humanos , Carcinoma Nasofaríngeo , Procesos Neoplásicos , Factor de Transcripción STAT3
9.
Exp Cell Res ; 403(1): 112585, 2021 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-33811905

RESUMEN

Cardiomyocytes are particularly prone to lipofuscin accumulation. In the aging heart, lipofuscin accumulation is augmented. This study examined distribution of lipofuscin and senescent cardiomyocytes and evaluated improvement of lipofuscin accumulation and cardiomyocytic senescence of the aging heart after treatment with rapamycin. The results of Schmorl staining, Sudan black staining and autofluorescence detection showed that there was more lipofuscin in the myocardium of the ventricles especially in the left ventricle. The conductive tissue contained less lipofuscin than the myocardium. In the aged hearts, lipofuscin accumulation and senescent cardiomyocytes were increased, and the level of autophagy was reduced. In double staining of Sudan black B and senescence-associated ß-galactosidase, 10%-20% lipofuscin-loaded cardiomyocytes became senescent. All senescent cardiomyocytes contained lipofuscin deposits. After enhancing autophagy with feed of rapamycin for six months, lipofuscin accumulation and senescence of cardiomyocytes were improved in old rats. Colocalization of autophagic structure and lipofuscin as well as electron micrographs showed that some lipofuscin-loaded lysosomes were sequestrated by autophagic structures. This study suggests that rapamycin-enhanced autopahgy is effective for reducing lipofuscinogenesis and promoting degradation of lipofuscin. Therefore, enhancing autophagy is a novel therapy for alleviating lipofuscin accumulation and myocardial senescence.


Asunto(s)
Envejecimiento/metabolismo , Autofagia/fisiología , Lisosomas/metabolismo , Miocitos Cardíacos/metabolismo , Animales , Células Cultivadas , Senescencia Celular/fisiología , Masculino , Miocardio/metabolismo , Ratas Sprague-Dawley , Coloración y Etiquetado/métodos
10.
J Clin Periodontol ; 49(10): 1067-1078, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35713233

RESUMEN

AIM: Periodontitis (PD) is the sixth most prevalent disease around the world and is involved in the development and progression of multiple systemic diseases. Previous studies have reported that PD may aggravate liver injuries. The objective of this study was to investigate whether and how PD affects liver fibrosis. MATERIALS AND METHODS: Ligature-induced PD (LIP) was induced in male C57/B6J mice, and sub-gingival plaques (PL) from patients with PD were applied to mouse teeth. Liver fibrosis was induced by carbon tetrachloride (CCl4 ) injection. The mice were randomly divided into six groups: Oil, Oil+LIP, Oil+LIP+PL, CCl4 , CCl4 +LIP, and CCl4 +LIP+PL. Alveolar bone resorption was evaluated by methylene blue staining. Hepatic function was analysed by serum alanine aminotransferase and hepatic hydroxyproline. Picrosirius red and α-smooth muscle actin (SMA) staining were used to evaluate the fibrotic area. RNA sequencing and quantitative RT-PCR were used to measure gene expression. Western blotting was used to measure protein levels. Flow cytometry was used to analyse the accumulation of immune cells. Mouse microbiota were analysed using 16S rRNA gene sequencing. RESULTS: Mice in the CCl4 +LIP+PL group displayed higher serum alanine aminotransferase and hepatic hydroxyproline as well as more Picrosirius red-positive and α-SMA-positive areas in liver samples than those of the CCl4 group, suggesting that PD (LIP+PL) aggravated CCl4 -induced hepatic dysfunction and liver fibrosis. Consistently, the expression of fibro-genic genes and the protein levels of transforming growth factor ß were much higher in the CCl4 +LIP+PL group than in the CCl4 group. Flow cytometry revealed that PD increased the accumulation of immune cells, including Kupffer cells, B cells, and Th17 cells, in the liver of mice with CCl4 treatment. PD also increased the expression of inflammatory genes and activated pro-inflammatory nuclear factor-kappa B pathway in the livers of CCl4 -injected mice. Moreover, PD altered both oral and liver microbiota in CCl4 -injected mice. CONCLUSIONS: PD aggravates CCl4 -induced hepatic dysfunction and fibrosis in mice, likely through the increase of inflammation and alteration of microbiota in the liver.


Asunto(s)
Cirrosis Hepática , Microbiota , Periodontitis , Actinas , Alanina Transaminasa , Animales , Compuestos Azo , Tetracloruro de Carbono/efectos adversos , Hidroxiprolina/metabolismo , Cirrosis Hepática/inducido químicamente , Masculino , Azul de Metileno , Ratones , Periodontitis/complicaciones , ARN Ribosómico 16S , Factor de Crecimiento Transformador beta/metabolismo
11.
Pharmazie ; 75(7): 313-317, 2020 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-32635972

RESUMEN

A magnetic targeting nanoparticle based on graphene oxide-ferroferric oxide (GO-Fe3O4) was investigated as a potential drug delivery vehicle. The formation of GO/Fe3O4 hybrid material was confirmed by Fourier transform infrared spectroscopy, X-ray diffraction, scanning electron microscopy and transmission electron microscopy. The GO/Fe3O4 hybrid still shows a higher saturation magnetization of 58.42 emu/g after coating with graphene oxide. Drug loading and releasing experiments demonstrate the GO-Fe3O4 hybrid has a good loading capacity of (6.47±0.08) mg/mg for temozolomide and a satisfactory release under slightly acidic condition. The MTT assays of glioma C6 cells exhibits the GO-Fe3O4 hybrid does not display toxicity with the concentration ranged from 40 to 120 µg/mL in vitro, while the complex of temozolomide loaded on GO/Fe3O4 has a better inhibitory effect on the proliferation of rat glioma C6 cells. All results suggest the prepared GO/Fe3O4 has potential applications in targeted anticancer drug delivery.


Asunto(s)
Neoplasias Encefálicas/tratamiento farmacológico , Sistemas de Liberación de Medicamentos , Glioma/tratamiento farmacológico , Temozolomida/administración & dosificación , Animales , Antineoplásicos Alquilantes/administración & dosificación , Antineoplásicos Alquilantes/farmacología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Portadores de Fármacos/química , Liberación de Fármacos , Grafito/química , Nanopartículas Magnéticas de Óxido de Hierro , Ratas , Temozolomida/farmacología
12.
Basic Res Cardiol ; 114(6): 43, 2019 10 06.
Artículo en Inglés | MEDLINE | ID: mdl-31587086

RESUMEN

Impairment of cardiac lymphatic vessels leads to cardiac lymphedema. Recent studies have suggested that stimulation of lymphangiogenesis may reduce cardiac lymphedema. However, effects of lymphatic endothelial progenitor cells (LEPCs) on cardiac lymphangiogenesis are poorly understood. Therefore, this study investigated effectiveness of LEPC transplantation and VEGF-C release with self-assembling peptide (SAP) on cardiac lymphangiogenesis after myocardial infarction (MI). CD34+VEGFR-3+ EPCs isolated from rat bone marrow differentiated into lymphatic endothelial cells after VEGF-C induction. VEGF-C also stimulated the cells to incorporate into the lymphatic capillary-like structures. The functionalized SAP could adhere with the cells and released VEGF-C sustainedly. In the condition of hypoxia and serum deprivation or abdominal pouch assay, the SAP hydrogel protected the cells from apoptosis and necrosis. At 4 weeks after intramyocardial transplantation of the cells and VEGF-C loaded with SAP hydrogel in rat MI models, cardiac lymphangiogenesis was increased, cardiac edema and reverse remodeling were reduced, and cardiac function was improved significantly. Delivery with SAP hydrogel favored survival of the engrafted cells. VEGF-C released from the hydrogel promoted differentiation and incorporation of the cells as well as growth of pre-existed lymphatic vessels. Cardiac lymphangiogenesis was beneficial for elimination of the inflammatory cells in the infarcted myocardium. Moreover, angiogenesis and myocardial regeneration were enhanced after reduction of lymphedema. These results demonstrate that the combined delivery of LEPCs and VEGF-C with the functionalized SAP promotes cardiac lymphangiogenesis and repair of the infarcted myocardium effectively. This study represents a novel therapy for relieving myocardial edema in cardiovascular diseases.


Asunto(s)
Edema Cardíaco/terapia , Células Progenitoras Endoteliales/trasplante , Linfangiogénesis , Factor C de Crecimiento Endotelial Vascular/uso terapéutico , Animales , Antígenos CD34/metabolismo , Células Progenitoras Endoteliales/metabolismo , Masculino , Miocardio/metabolismo , Neovascularización Fisiológica , Ratas Sprague-Dawley , Factor A de Crecimiento Endotelial Vascular/sangre , Factor C de Crecimiento Endotelial Vascular/sangre , Receptor 3 de Factores de Crecimiento Endotelial Vascular/metabolismo
13.
Exp Cell Res ; 362(1): 17-27, 2018 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-28987540

RESUMEN

Serelaxin, a recombinant form of human relaxin-2, is currently regarded as a novel drug for treatment of acute heart failure. However, whether therapeutic effects of serelaxin are achieved by inhibiting cardiac fibrosis remains unclear. In this study, we investigate effects of serelaxin on inhibiting cardiac fibrosis. Cardiac fibroblasts (CFs) were isolated from the hearts of adult rats. Effects of serelaxin on differentiation of CFs towards myofibroblasts (MFs) and their fibrotic behaviors after induction with TGF-ß1 were examined. Synthesis and degradation of collagens, secretion of IL-10, and expression of ALK-5 and p-Smad2/3 of TGF-ß1-induced cells were assessed after treatment with serelaxin. Serelaxin inhibited differentiation of TGF-ß1-induced CFs towards MFs, and reduced proliferation and migration of the induced cells. Moreover, serelaxin down-regulated expression of collagen I/III and TIMP-2, and up-regulated expression of MMP-2 and MMP-9 in the cells. After treatment with serelaxin, activity of MMP-2 and MMP-9 and secretion of IL-10 increased, expression of ALK-5 and the level of Smad2/3 phosphorylation was reduced significantly. These results suggest that serelaxin can inhibit differentiation of TGF-ß1-induced CFs towards MFs, reduce production of collagens by suppressing ALK-5/Smad2/3 signaling pathway, and enhance extracellular matrix degradation by increasing MMP-2/TIMP-2 ratio and IL-10 secretion. Serelaxin may be a potential therapeutic drug for inhibiting cardiac fibrosis.


Asunto(s)
Diferenciación Celular/efectos de los fármacos , Miocardio/patología , Miocitos Cardíacos/efectos de los fármacos , Miofibroblastos/efectos de los fármacos , Relaxina/farmacología , Animales , Células Cultivadas , Regulación hacia Abajo/efectos de los fármacos , Femenino , Fibrosis/metabolismo , Fibrosis/prevención & control , Humanos , Miocardio/metabolismo , Miocitos Cardíacos/patología , Miocitos Cardíacos/fisiología , Proteínas Serina-Treonina Quinasas/metabolismo , Ratas , Ratas Sprague-Dawley , Receptor Tipo I de Factor de Crecimiento Transformador beta , Receptores de Factores de Crecimiento Transformadores beta/metabolismo , Proteínas Recombinantes/farmacología , Transducción de Señal/efectos de los fármacos , Proteína Smad2/metabolismo , Proteína smad3/metabolismo
14.
Asian-Australas J Anim Sci ; 32(2): 233-240, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30145865

RESUMEN

OBJECTIVE: This study was to investigate the effects of dietary cotton stalk on nitrogen and free gossypol in sheep. METHODS: Treatments included 25% cotton stalk (Treat 1), 50% cotton stalk (Treat 2), and a control (no cotton stalk). Six Xinjiang daolang wethers were cannulated at the rumen and duodenum and fed one of these diets. The effects of these diets on nitrogen and free gossypol absorption and metabolism were determined. Fifteen healthy Xinjiang daolang wethers were assessed for daily gain, tissue lesions, and free gossypol accumulation. RESULTS: Dry matter intake decreased with increasing dietary cotton stalk. Total tract dry matter digestibility did not significantly differ among treatments. Dietary cotton stalk significantly decreased volatile fatty acids and increased ammonium nitrogen in the rumen. Nitrogen intake was significantly higher in Treat 2 than in the control or Treat 1. Nitrogen retention and free gossypol intake increased with dietary cotton stalk. Duodenal free gossypol flow did not increase, and free gossypol almost disappeared from the rumen. The free gossypol content of plasma and tissue was increased with dietary cotton stalk with liver free gossypol> muscle free gossypol>kidney free gossypol. Elevated dietary free gossypol decreased platelets, hemoglobin, and serum iron. Aspartate aminotransferase and γ-glutamyltransferase increased in Treat 2. With high long-term dietary cotton stalk intake, liver cells were swollen, and their nuclei dissolved. Renal cells were necrotic and the interstitia were enlarged. CONCLUSION: With short-term cotton stalk administration, only a small amount of free gossypol is retained in the body. In response to long-term or high free gossypol cotton stalk feeding, however, free gossypol accumulates in, and damages the liver and kidneys.

15.
J Cell Mol Med ; 21(9): 1751-1766, 2017 09.
Artículo en Inglés | MEDLINE | ID: mdl-28244640

RESUMEN

Cardiac patch is considered a promising strategy for enhancing stem cell therapy of myocardial infarction (MI). However, the underlying mechanisms for cardiac patch repairing infarcted myocardium remain unclear. In this study, we investigated the mechanisms of PCL/gelatin patch loaded with MSCs on activating endogenous cardiac repair. PCL/gelatin patch was fabricated by electrospun. The patch enhanced the survival of the seeded MSCs and their HIF-1α, Tß4, VEGF and SDF-1 expression and decreased CXCL14 expression in hypoxic and serum-deprived conditions. In murine MI models, the survival and distribution of the engrafted MSCs and the activation of the epicardium were examined, respectively. At 4 weeks after transplantation of the cell patch, the cardiac functions were significantly improved. The engrafted MSCs migrated across the epicardium and into the myocardium. Tendency of HIF-1α, Tß4, VEGF, SDF-1 and CXCL14 expression in the infarcted myocardium was similar with expression in vitro. The epicardium was activated and epicardial-derived cells (EPDCs) migrated into deep tissue. The EPDCs differentiated into endothelial cells and smooth muscle cells, and some of EPDCs showed to have differentiated into cardiomyocytes. Density of blood and lymphatic capillaries increased significantly. More c-kit+ cells were recruited into the infarcted myocardium after transplantation of the cell patch. The results suggest that epicardial transplantation of the cell patch promotes repair of the infarcted myocardium and improves cardiac functions by enhancing the survival of the transplanted cells, accelerating locality paracrine, and then activating the epicardium and recruiting endogenous c-kit+ cells. Epicardial transplantation of the cell patch may be applied as a novel effective MI therapy.


Asunto(s)
Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas/citología , Infarto del Miocardio/patología , Infarto del Miocardio/terapia , Miocardio/patología , Regeneración , Animales , Materiales Biocompatibles/química , Capilares/patología , Diferenciación Celular/genética , Supervivencia Celular/genética , Quimiocinas/metabolismo , Citoprotección , Gelatina/química , Regulación de la Expresión Génica , Pruebas de Función Cardíaca , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Linfangiogénesis/genética , Masculino , Células Madre Mesenquimatosas/ultraestructura , Ratones , Infarto del Miocardio/fisiopatología , Neovascularización Fisiológica , Poliésteres/química , Proteínas Proto-Oncogénicas c-kit/metabolismo , Ratas Sprague-Dawley , Timosina/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo
16.
Tumour Biol ; 39(7): 1010428317707435, 2017 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-28714364

RESUMEN

The aim of this study is investigate the influence of endoscopic sinus surgery on the quality of life and prognosis of patients with early nasopharyngeal carcinoma. Patients initially diagnosed with early nasopharyngeal carcinoma and received surgical treatment were matched with nasopharyngeal carcinoma patients who received chemoradiotherapy at a ratio of 1:1, according to the following seven factors: gender, age, T staging, N staging, clinical staging, radiotherapy options, and chemotherapy options. Patients in the surgery group received endoscopic sinus surgery plus chemoradiotherapy, while subjects in the control group received chemoradiotherapy. The quality of life of patients before and after treatment was evaluated based on the FACT-H&N (Functional Assessment of Cancer Therapy-Head and Neck) and QLQ-H&N35 (Head and Neck Cancer Specific Module) questionnaires. In addition, overall survival and disease-free survival were compared between these two groups. The results showed overall survival was superior in the surgery group compared with the control group ( p = 0.007). However, the difference in disease-free survival between these two groups was not statistically significant ( p = 0.128). Furthermore, subgroup analysis revealed that for N0 patients, the effect of surgery combined with chemoradiotherapy on overall survival was superior to that of chemoradiotherapy ( p = 0.048); while for N1 patients, the difference in overall survival between these two groups was not statistically significant ( p = 0.065). For early nasopharyngeal carcinoma patients without lymph node metastasis, overall survival and disease-free survival in T1 patients were superior to those in T2 patients (χ2 = 4.403, p = 0.036; χ2 = 4.542, p = 0.033). At the end of treatment, the pain score was found to be significantly lower in the surgery group than in the chemoradiotherapy group ( p = 0.027). At 3 months and 1 year after treatment, dry mouth scores were significantly lower in the surgery group than in the chemoradiotherapy group ( p = 0.002, p = 0.026). These results demonstrated that the curative effect of surgery combined with chemoradiotherapy in the treatment of nasopharyngeal carcinoma was satisfactory and was particularly suitable for N0 patients.


Asunto(s)
Carcinoma/tratamiento farmacológico , Carcinoma/radioterapia , Carcinoma/cirugía , Neoplasias Nasofaríngeas/tratamiento farmacológico , Neoplasias Nasofaríngeas/radioterapia , Neoplasias Nasofaríngeas/cirugía , Senos Paranasales/cirugía , Adolescente , Adulto , Anciano , Carcinoma/patología , Terapia Combinada , Supervivencia sin Enfermedad , Endoscopía , Femenino , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/patología , Estadificación de Neoplasias , Senos Paranasales/patología , Pronóstico , Calidad de Vida
17.
Eur Radiol ; 27(9): 3694-3702, 2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-28124747

RESUMEN

OBJECTIVE: To analyze the outcomes of a magnesium alloy covered stent (MACS) for a lateral aneurysm model in common carotid artery (CCA). METHODS: In 32 rabbits, a MACS (group A, n = 17) or a Willis covered stent (WCS; group B, n = 15) was inserted and the rabbits were sacrificed 1, 3, 6, or 12 months after stenting. Angiography and intravascular ultrasound (IVUS) were performed at 3, 6, and 12 months. Scanning electron microscopy was performed for six stents in each group at 1, 3, and 6 months, and histopathology and histomorphology were conducted at 3 (n = 4), 6 (n = 4), and 12 (n = 12) months. RESULTS: Final angiography showed complete occlusion of the aneurysms in 12 cases. IVUS at 6 and 12 months revealed a significant increase in mean lumen area of the stented CCA in group A and also showed greater mean lumen area in group A than in group B. The endothelialization process was quicker in group A than in group B. CONCLUSION: MACS is effective for occlusion of lateral aneurysms and is superior to WCS in growth of the stented CCA and endothelialization. Further work is needed to make this device available for human use. KEY POINTS: • The MACS is an effective approach for occlusion of a lateral aneurysm. • IVUS showed that the CCA could grow following degradation of the MACS. • The lumen area of the stented CCA was excellent in MACS. • HE staining displayed the degradation of the magnesium alloy stent. • Combination of IVUS and DSA were applied in this study.


Asunto(s)
Aleaciones/química , Aneurisma/cirugía , Enfermedades de las Arterias Carótidas/cirugía , Materiales Biocompatibles Revestidos , Magnesio , Stents , Procedimientos Quirúrgicos Vasculares/instrumentación , Angiografía , Animales , Arterias Carótidas , Arteria Carótida Común/cirugía , Modelos Animales de Enfermedad , Masculino , Conejos , Resultado del Tratamiento
18.
Eur Spine J ; 26(5): 1454-1462, 2017 05.
Artículo en Inglés | MEDLINE | ID: mdl-27388020

RESUMEN

PURPOSES: To discuss whether radiologic parameters are closely related to posterior ligamentous complex (PLC) injury identified by magnetic resonance imaging (MRI). METHODS: One hundred and five thoracolumbar fracture (T11-L2) patients were retrospectively analyzed in the study. The patients were divided into different groups by the status of the PLC on MRI: intact, incompletely ruptured and ruptured. The radiographic parameters included the anterior edge-inferior endplate angle (AEIEA), the anterior edge displacement (AED), the Cobb angle (CA), the region angle (RA), the sagittal index (SI), local kyphosis (LK), the anterior/posterior vertebral height ratio (A/P ratio), the anterior vertebral height ratio (AVH ratio), and bony fragment in front of the fractured vertebra (BFOFV). T test, Pearson's Chi-square and multivariate logistic regression were calculated for the variables. RESULTS: Supraspinous ligament (SSL) rupture versus intact was not only associated with the occurrence of AEIEA <70°, LK >25° and BFOFV, but also with increased AED (9.89 ± 3.12 mm and 9.34 ± 3.36 mm, P = 0.034), RA (9.52 ± 3.93° versus 7.91 ± 3.99°, P = 0.042), and LK (23.98 ± 5.88° versus 15.55 ± 5.28°, P = 0.021). The indications for interspinous ligament (ISL) injury included AEIEA <75°, AEIEA <70° (P = 0.004 and P < 0.001, respectively), increased AED (P = 0.010), LK >25° (P = 0.024), AVH (P < 0.001), and BFOFV (P < 0.001). Multivariate logistic regression analysis revealed that AEIEA <70° and BFOFV were high risk factors for SSL rupture [standard partial regression coefficients (betas) were 0.439 and 0.408, P = 0.003 and 0.001, respectively] and ISL rupture (betas were 0.548 and 0.494, P = 0.028 and 0.001, respectively). Increased AED and LK >25° were also related to either ISL rupture (P = 0.035 and 0.001, respectively) or SSL rupture (P = 0.014 and 0.008, respectively). CONCLUSION: Our data may prove useful in a preliminary assessment of the PLC integrity based on plain radiographic imaging. We show that radiologic indications, such as AEIEA <70°, BFOFV, LK >25°, and increased AED, are correlated with ISL or SSL rupture, while RA, CA, SI, A/P ratio, and AVH ratio are not.


Asunto(s)
Ligamentos Longitudinales/diagnóstico por imagen , Ligamentos Longitudinales/lesiones , Vértebras Lumbares/diagnóstico por imagen , Fracturas de la Columna Vertebral/diagnóstico por imagen , Vértebras Torácicas/diagnóstico por imagen , Adulto , Femenino , Humanos , Vértebras Lumbares/lesiones , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Vértebras Torácicas/lesiones , Adulto Joven
19.
Eur Spine J ; 26(1): 221-227, 2017 01.
Artículo en Inglés | MEDLINE | ID: mdl-27832363

RESUMEN

PURPOSE: The aim of this study was to develop a novel method for observing the morphology of the blood vessels in the rabbit endplate. METHODS: Twenty 6-month-old rabbits were used in this study. The blood vessels in the L5 endplate in Group A were injected with iohexol and Group B with barium sulfate. Group C was the control group with saline. To optimize the study, Group B was divided into two subgroups: Group B-1 was injected with 100% (w/v) barium sulfate and Group B-2 with 50% (w/v). After injection, the L4-L5 vertebral body was excised and the cranial endplate of L5 was scanned using a micro-CT scanner. Models of the vertebral endplate and vessels were reconstructed using the 3D reconstruction software (Mimics 16.0) by calculating a bone threshold value, and then merged these two models to create a superimposed model. RESULTS: The 3D vessel models could not be created in Groups A and C, but they were clearly visualized in Group B. In the 3D model, the blood vessels extended from the subchondral bone to the endplate, and the density of the blood vessels in the area of the nucleus pulposus (NP) was higher than in the annulus fibrosus. CONCLUSIONS: The results of this study suggest that the blood vessels in the rabbit endplate can be clearly observed by the method described using barium sulfate [the 50% (w/v) gave better results compared with the 100% (w/v)]. The information from the 3D vessel structure could provide essential data to help us understand the nutrient pathways within the vertebral endplate.


Asunto(s)
Disco Intervertebral/irrigación sanguínea , Vértebras Lumbares/irrigación sanguínea , Microtomografía por Rayos X , Animales , Medios de Contraste , Imagenología Tridimensional , Conejos
20.
Eur Spine J ; 25(6): 1661-4, 2016 06.
Artículo en Inglés | MEDLINE | ID: mdl-26831537

RESUMEN

PURPOSE: To describe and illustrate a modified technique for using translaminar screw in the cervicothoracic junction (C7-T2). METHODS: 12 patients (8 males and 4 females, average age was 52 years) underwent insertion of unilateral or bilateral translaminar screws by using our modified technique. With this modified technique, a tiny unicortical "hole" was made at the middle of the contralateral lamina, and the screw can be directly visualized through the unicortical "hole" to prevent violating the spinal canal. RESULTS: With this modified technique, the mean operation time was 205 min (range 145-360) and mean estimated blood loss was 445 ml (range 260-1250). The mean length of the laminar screws was 27 (range 24-30) mm. The results of the 12 patients with an average follow-up of 17 (6-33) months demonstrated this modified technique to be safe and effective in the fixation of cervicothoracic junction. CONCLUSION: In this modified technique, a tiny unicortical "hole" which was made at the middle of the dorsal lamina of cervicothoracic junction (C7-T2). By directly visualizing the screw inserting against the dorsal cortices of the lamina, this modified technique can reduce the risk of violation of the spinal canal and shorten the operation time.


Asunto(s)
Tornillos Óseos , Vértebras Cervicales/cirugía , Fusión Vertebral , Vértebras Torácicas/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tempo Operativo , Fusión Vertebral/instrumentación , Fusión Vertebral/métodos
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