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1.
Clinics (Sao Paulo) ; 78: 100181, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36948071

RESUMEN

OBJECTIVES: This study aimed to explore the effects of bone marrow-derived Mesenchymal Stem Cell-Conditioned Medium (MSC-CM) treating diabetic foot ulcers in rats. METHODS: Models of T2DM rats were induced by a high-fat diet and intraperitoneal injection of STZ in SD rats. Models of Diabetic Foot Ulcers (DFUs) were made by operation on hind limbs in diabetic rats. Rats were divided into four groups (n = 6 for each group), i.e., Normal Control group (NC), Diabetes Control group (DM-C), MSC-CM group and Mesenchymal Stem Cells group (MSCs). MSC-CM group was treated with an injection of conditioned medium derived from preconditioned rats' bone marrow MSCs around ulcers. MSCs group were treated with an injection of rats' bone marrow MSCs. The other two groups were treated with an injection of PBS. After the treatment, wound closure, re-epithelialization (thickness of the stratum granulosums of the skin, by H&E staining), cell proliferation (Ki67, by IHC), angiogenesis (CD31, by IFC), autophagy (LC3B, by IFC and WB; autolysosome, by EM) and pyroptosis (IL-1ß, NLRP3, Caspase-1, GSDMD and GSDMD-N, by WB) in ulcers were evaluated. RESULTS: After the treatment wound area rate, IL-1ß by ELISA, and IL-1ß, Caspase-1, GSDMD and GSDMD-N by WB of MSC-CM group were less than those of DM group. The thickness of the stratum granulosums of the skin, proliferation index of Ki67, mean optic density of CD31 and LC3B by IFC, and LC3B by WB of MSC-CM group were more than those of DM group. The present analysis demonstrated that the injection of MSC-CM into rats with DFUs enhanced the wound-healing process by accelerating wound closure, promoting cell proliferation and angiogenesis, enhancing cell autophagy, and reducing cell pyroptosis in ulcers. CONCLUSIONS: Studies conducted indicate that MSC-CM administration could be a novel cell-free therapeutic approach to treat DFUs accelerating the wound healing process and avoiding the risk of living cells therapy.


Asunto(s)
Diabetes Mellitus Experimental , Pie Diabético , Células Madre Mesenquimatosas , Ratas , Animales , Pie Diabético/terapia , Medios de Cultivo Condicionados/farmacología , Diabetes Mellitus Experimental/complicaciones , Médula Ósea , Antígeno Ki-67 , Ratas Sprague-Dawley , Caspasas
4.
Clinics ; Clinics;78: 100181, 2023. tab, graf
Artículo en Inglés | LILACS-Express | LILACS | ID: biblio-1439899

RESUMEN

Abstract Objectives: This study aimed to explore the effects of bone marrow-derived Mesenchymal Stem Cell-Conditioned Medium (MSC-CM) treating diabetic foot ulcers in rats. Methods: Models of T2DM rats were induced by a high-fat diet and intraperitoneal injection of STZ in SD rats. Models of Diabetic Foot Ulcers (DFUs) were made by operation on hind limbs in diabetic rats. Rats were divided into four groups (n = 6 for each group), i.e., Normal Control group (NC), Diabetes Control group (DM-C), MSC-CM group and Mesenchymal Stem Cells group (MSCs). MSC-CM group was treated with an injection of conditioned medium derived from preconditioned rats' bone marrow MSCs around ulcers. MSCs group were treated with an injection of rats' bone marrow MSCs. The other two groups were treated with an injection of PBS. After the treatment, wound closure, re-epithelialization (thickness of the stratum granulosums of the skin, by H&E staining), cell proliferation (Ki67, by IHC), angiogenesis (CD31, by IFC), autophagy (LC3B, by IFC and WB; autoly-sosome, by EM) and pyroptosis (IL-1β, NLRP3, Caspase-1, GSDMD and GSDMD-N, by WB) in ulcers were evaluated. Results: After the treatment wound area rate, IL-1β by ELISA, and IL-1β, Caspase-1, GSDMD and GSDMD-N by WB of MSC-CM group were less than those of DM group. The thickness of the stratum granulosums of the skin, proliferation index of Ki67, mean optic density of CD31 and LC3B by IFC, and LC3B by WB of MSC-CM group were more than those of DM group. The present analysis demonstrated that the injection of MSC-CM into rats with DFUs enhanced the wound-healing process by accelerating wound closure, promoting cell proliferation and angiogenesis, enhancing cell autophagy, and reducing cell pyroptosis in ulcers. Conclusions: Studies conducted indicate that MSC-CM administration could be a novel cell-free therapeutic approach to treat DFUs accelerating the wound healing process and avoiding the risk of living cells therapy.

5.
Rev Assoc Med Bras (1992) ; 64(2): 175-180, 2018 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-29641671

RESUMEN

OBJECTIVE: The present study aimed to investigate the analgesic effect and safety of using local incision analgesia to treat acute postoperative pain in patients with hepatocellular carcinoma (HCC). METHOD: A cohort of 60 patients undergoing liver cancer resection was randomly divided into three groups (n=20 per group): local incision analgesia (LIA) group, which received local infiltration with ropivacaine combined with a postoperative analgesia pump; intravenous patient-controlled analgesia (PCA) group, which received fentanyl intravenous analgesia postoperatively; and the control group, which received tramadol hydrochloride injection postoperatively according to the NRS scoring system. The postoperative analgesic effect in each group was compared and tumor recurrence (survival) was analyzed using the Kaplan-Meier method. RESULTS: NRS scores, rate of analgesic usage, ambulation time (h) and intestinal function recovery time (h) were significantly reduced in LIA group compared with the control group at each postoperative time point (6, 12, 24 and 48 hours; p<0.05). Additionally, the NRS scores of LIA patients at 12 hours post-surgery was significantly reduced compared with PCA group (p<0.05), and the occurrence of postoperative adverse events in LIA group was significantly lower than that in PCA group (p<0.05). Survival analysis demonstrated that the mean survival time (tumor recurrence) was significantly increased in LIA group compared with the control group (χ2=4.749; p=0.029). CONCLUSION: Local incision analgesia improves the analgesic effect, causes fewer adverse reactions and increases postoperative survival time. Our study demonstrated that local incision analgesia is a safe and effective method of postoperative pain management following hepatectomy.


Asunto(s)
Dolor Agudo/tratamiento farmacológico , Analgésicos Opioides/uso terapéutico , Anestésicos Locales/uso terapéutico , Carcinoma Hepatocelular/cirugía , Neoplasias Hepáticas/cirugía , Dolor Postoperatorio/tratamiento farmacológico , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Manejo del Dolor/efectos adversos , Manejo del Dolor/métodos , Dimensión del Dolor , Análisis de Supervivencia , Resultado del Tratamiento
6.
Rev. Assoc. Med. Bras. (1992, Impr.) ; Rev. Assoc. Med. Bras. (1992, Impr.);64(2): 175-180, Feb. 2018. tab, graf
Artículo en Inglés | LILACS | ID: biblio-896431

RESUMEN

Summary Objective: The present study aimed to investigate the analgesic effect and safety of using local incision analgesia to treat acute postoperative pain in patients with hepatocellular carcinoma (HCC). Method: A cohort of 60 patients undergoing liver cancer resection was randomly divided into three groups (n=20 per group): local incision analgesia (LIA) group, which received local infiltration with ropivacaine combined with a postoperative analgesia pump; intravenous patient-controlled analgesia (PCA) group, which received fentanyl intravenous analgesia postoperatively; and the control group, which received tramadol hydrochloride injection postoperatively according to the NRS scoring system. The postoperative analgesic effect in each group was compared and tumor recurrence (survival) was analyzed using the Kaplan-Meier method. Results: NRS scores, rate of analgesic usage, ambulation time (h) and intestinal function recovery time (h) were significantly reduced in LIA group compared with the control group at each postoperative time point (6, 12, 24 and 48 hours; p<0.05). Additionally, the NRS scores of LIA patients at 12 hours post-surgery was significantly reduced compared with PCA group (p<0.05), and the occurrence of postoperative adverse events in LIA group was significantly lower than that in PCA group (p<0.05). Survival analysis demonstrated that the mean survival time (tumor recurrence) was significantly increased in LIA group compared with the control group (χ2=4.749; p=0.029). Conclusion: Local incision analgesia improves the analgesic effect, causes fewer adverse reactions and increases postoperative survival time. Our study demonstrated that local incision analgesia is a safe and effective method of postoperative pain management following hepatectomy.


Asunto(s)
Humanos , Masculino , Femenino , Adulto , Dolor Postoperatorio/tratamiento farmacológico , Carcinoma Hepatocelular/cirugía , Dolor Agudo/tratamiento farmacológico , Analgésicos Opioides/uso terapéutico , Anestésicos Locales/uso terapéutico , Dimensión del Dolor , Análisis de Supervivencia , Resultado del Tratamiento , Manejo del Dolor/efectos adversos , Manejo del Dolor/métodos , Persona de Mediana Edad , Recurrencia Local de Neoplasia
8.
Mol Cell ; 65(1): 52-65, 2017 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-27916661

RESUMEN

Tetrameric assembly of channel subunits in the endoplasmic reticulum (ER) is essential for surface expression and function of K+ channels, but the molecular mechanism underlying this process remains unclear. In this study, we found through genetic screening that ER-located J-domain-containing chaperone proteins (J-proteins) are critical for the biogenesis and physiological function of ether-a-go-go-related gene (ERG) K+ channels in both Caenorhabditis elegans and human cells. Human J-proteins DNAJB12 and DNAJB14 promoted tetrameric assembly of ERG (and Kv4.2) K+ channel subunits through a heat shock protein (HSP) 70-independent mechanism, whereas a mutated DNAJB12 that did not undergo oligomerization itself failed to assemble ERG channel subunits into tetramers in vitro and in C. elegans. Overexpressing DNAJB14 significantly rescued the defective function of human ether-a-go-go-related gene (hERG) mutant channels associated with long QT syndrome (LQTS), a condition that predisposes to life-threatening arrhythmia, by stabilizing the mutated proteins. Thus, chaperone proteins are required for subunit stability and assembly of K+ channels.


Asunto(s)
Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/metabolismo , Canal de Potasio ERG1/metabolismo , Retículo Endoplásmico/metabolismo , Proteínas del Choque Térmico HSP40/metabolismo , Proteínas del Choque Térmico HSP47/metabolismo , Canales de Potasio/metabolismo , Animales , Animales Modificados Genéticamente , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/química , Proteínas de Caenorhabditis elegans/genética , Línea Celular Tumoral , Canal de Potasio ERG1/química , Canal de Potasio ERG1/genética , Células HEK293 , Proteínas del Choque Térmico HSP40/química , Proteínas del Choque Térmico HSP40/genética , Proteínas del Choque Térmico HSP47/química , Proteínas del Choque Térmico HSP47/genética , Proteínas HSP70 de Choque Térmico/metabolismo , Humanos , Células Madre Pluripotentes Inducidas/metabolismo , Síndrome de QT Prolongado/genética , Síndrome de QT Prolongado/metabolismo , Potenciales de la Membrana , Chaperonas Moleculares , Mutación , Miocitos Cardíacos/metabolismo , Canales de Potasio/química , Canales de Potasio/genética , Multimerización de Proteína , Estabilidad Proteica , Estructura Cuaternaria de Proteína , Interferencia de ARN , Canales de Potasio Shal/genética , Canales de Potasio Shal/metabolismo , Factores de Tiempo , Transfección
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