Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 29
Filtrar
Más filtros












Base de datos
Intervalo de año de publicación
1.
Am J Transl Res ; 15(2): 1063-1071, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36915784

RESUMEN

OBJECTIVES: This study aimed to investigate the regulation function of acupuncture on airway smooth muscle cells (ASMCs) of asthmatic rats. METHODS: Male Sprague-Dawley rats were challenged using inhalational Ovalbumin (OVA) to establish an asthma model. The acupuncture points (GV14 for Dazhui, bilateral BL12 for Fengmen, and bilateral BL13 for Feishu) were stimulated for asthma relief. The ASMCs isolated from asthmatic rats were incubated in medium containing the serum obtained from asthmatic rats treated with acupuncture. The expression levels of p38 MAPK and p-p38 MAPK were determined by immunocytochemical and western blot. RESULTS: ASMCs were successfully isolated and cultured. The 20% acupuncture treatment of asthmatic rat serum had the least effect on the proliferation ability of asthmatic ASMCs. The serum from asthmatic rats treated with acupuncture could decrease the expression of p-p38 MAPK in asthmatic rat ASMCs. CONCLUSIONS: The serum from acupuncture-treated asthmatic rats has an effect on treating asthma in rats, and the mechanism of action may be by regulating the p38 pathway.

2.
Neurotoxicology ; 95: 107-116, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36642386

RESUMEN

Pb can enhance blood-cerebrospinal fluid barrier (BCSFB) permeability and accumulate in brain tissue, leading to central nervous system (CNS) dysfunction. Choroid plexus (CP) epithelial cells are the main components of the BCSFB with crucial functions in BCSFB maintenance. However, the mechanism by which Pb exposure affects CP epithelial cells remains unclear. Here, ferroptosis was identified as the major programmed cell death modality by sophisticated high-throughput sequencing and biochemical investigations in primary cultured CP epithelial cells following Pb exposure. Bioinformatics analysis using the ferroptosis database revealed that 16 ferroptosis-related genes were differentially expressed in primary cultured CP epithelial cells following Pb exposure. Among them, Gpx4, Slc7a11, Tfrc, and Slc40a1 were hub ferroptosis-related genes. In addition, CP epithelial cells can be impaired when the concentration of the Pb2+ reached 2050 µg/L (10 µM PbAc), which included the decrease of cell viability, Gpx4 and Slc7a11 proteins expression, etc. Moreover, inhibition of ferroptosis enhanced CP epithelial cell viability and reduced BCSFB permeability in vitro following Pb exposure. In summary, ferroptosis of CP epithelial cells is involved in BCSFB dysfunction following Pb exposure. Gpx4, Slc7a11, Tfrc, and Slc40a1 are hub ferroptosis-related genes in CP epithelial cells.


Asunto(s)
Ferroptosis , Plomo , Barrera Hematoencefálica/metabolismo , Plexo Coroideo/metabolismo , Células Epiteliales/metabolismo , Plomo/metabolismo , Hierro/metabolismo
3.
Ann Noninvasive Electrocardiol ; 27(6): e12996, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-35894768

RESUMEN

OBJECTIVE: This study investigated the effects of aerobic exercise combined with resistance training on serum inflammatory factors and heart rate variability (HRV) in women with type 2 diabetes mellitus (T2DM). METHODS: A total of 30 patients with diabetic cardiovascular autonomic neuropathy (DCAN) were randomly divided into a control group (n = 15) and an exercise group (n = 15). The control group was treated with routine hypoglycemic drugs, while the exercise group was treated with routine hypoglycemic drugs + resistance training (AE + RT). The levels of fasting plasma glucose (FBG), two-hour plasma glucose (2hPG), serum inflammatory factors C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) were measured before and after the intervention. The HRV was evaluated by 24-h ambulatory electrocardiogram. RESULTS: After the intervention, the levels of FBG, 2hPG, serum inflammatory factors, IL-6 and TNF-α in the exercise group were significantly lower than those in the control group (p < .05) with no significant differences in serum CRP (p > .05). After the intervention, the HRV time domain and frequency domain indexes in the two groups were significantly improved compared with those before the exercise experiment (p < .01) and with no significant difference in (lnlf) (p > .05). The time-domain indexes, i.e., SDNN and RMSSD, as well as the frequency domain index, i.e., (lnhf), were significantly higher in the exercise group than in the control group, whereas lnlf/lnhf were significantly lower than those in the control group (p < .05). CONCLUSIONS: Compared with routine hypoglycemic drug therapy, combining aerobic exercise and resistance training helped to reduce the level of blood glucose and serum inflammatory factors in T2DM patients with DCAN, and improved autonomic nerve function.


Asunto(s)
Diabetes Mellitus Tipo 2 , Entrenamiento de Fuerza , Persona de Mediana Edad , Anciano , Humanos , Femenino , Frecuencia Cardíaca/fisiología , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/terapia , Glucemia/metabolismo , Factor de Necrosis Tumoral alfa , Interleucina-6 , Terapia por Ejercicio , Electrocardiografía , Ejercicio Físico/fisiología , Hipoglucemiantes/uso terapéutico
4.
Ecotoxicol Environ Saf ; 239: 113639, 2022 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-35588615

RESUMEN

An increasing number of studies have clarified that ferroptosis plays a vital role in neurodegenerative diseases, which is characterized by the accumulation of Fe2+, lipid peroxidation, and alteration of mitochondrial structure. However, whether ferroptosis is involved in nerve injury caused by lead exposure remains unclear. In this study, HT22 cells and mice were treated with lead acetate to investigate the role of ferroptosis in lead neurotoxicity. The results showed that lead exposure resulted in an accumulation of Fe2+, an increase in malondialdehyde (MDA) levels, and a decrease in glutathione (GSH) levels in vivo and in vitro. An increase in the levels of lipid reactive oxygen species (ROS) and the expression of 4HNE, as well as the change in mitochondrial morphology, were also observed in HT22 cells treated with lead acetate. In addition, deferoxamine (DFO; an iron chelator) attenuated the accumulation of Fe2+ and significantly enhanced the viability of HT22 cells exposed to lead. Fer-1 (an anti-ferroptosis agent) reduced the level of lipid ROS and expression of 4HNE in lead-treated HT22 cells. Furthermore, lead exposure sharply downregulated the expression of SLC7A11 in HT22 cells. Overexpression of SLC7A11 reversed the changes in MDA and GSH levels and cell viability induced by lead exposure. In contrast, lower expression of SLC7A11 accelerated the changes in these parameters. Consequently, we screened miRNAs that regulate SLC7A11 using TargetScan. We found that miR-378a-3p showed the highest expression among the target miRNAs regulating SLC7A11 expression. Inhibition of miR-378a-3p expression reversed the reduction in GSH and the increase in lipid ROS levels induced by lead exposure. Taken together, these findings indicate that lead exposure can cause ferroptosis and that miR-378a-3p exerted an important effect by regulating SLC7A11 expression. Our findings provide new insights into the mechanisms underlying the effects of lead exposure.


Asunto(s)
Sistema de Transporte de Aminoácidos y+ , Plomo , MicroARNs , Neuronas , Acetatos , Sistema de Transporte de Aminoácidos y+/genética , Animales , Plomo/toxicidad , Lípidos , Ratones , MicroARNs/genética , Neuronas/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo
5.
Zhongguo Zhen Jiu ; 40(1): 54-7, 2020 Jan 12.
Artículo en Chino | MEDLINE | ID: mdl-31930900

RESUMEN

The value of the "touching-bone" acupuncture technique in clinical application was explained through the investigation on the origin of the theory of the "touching-bone" acupuncture technique, the analysis on the characteristics of acupoint selection, the introduction of clinical characteristics and the discussion on the mechanism of acupuncture in treatment. The "touching-bone" acupuncture technique refers to deep needling method, originated from the short needling and shu needling of the ancient needling methodslisted in the Internal Classic. The target points are the reaction sites on meridian near to bone and the attachments of soft tissues on bone. During the needle insertion, the needle tip is thrust deeply to the bone or the needle body is closely attached to the bone so as to stimulate periosteum specifically. This needling technique contributes to the satisfactory effect on spasmodic, deep-located and intractable pain disorder, motor system diseases, mental diseases and cerebral diseases, etc. Hence, this acupuncture technique deserves to be promoted in clinical application and explored in research.


Asunto(s)
Terapia por Acupuntura , Meridianos , Agujas
6.
FEMS Microbiol Lett ; 365(15)2018 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-30007321

RESUMEN

Sec-dependent protein translocation is an essential process in bacteria. SecA is a key component of the translocation machinery and has multiple domains that interact with various ligands. SecA acts as an ATPase motor to drive the precursor protein/peptide through the SecYEG protein translocation channels. As SecA is unique to bacteria and there is no mammalian counterpart, it is an ideal target for the development of new antimicrobials. Several reviews detail the assays for ATPase and protein translocation, as well as the search for SecA inhibitors. Recent studies have shown that, in addition to the SecA-SecYEG translocation channels, there are SecA-only channels in the lipid bilayers, which function independently from the SecYEG machinery. This mini-review focuses on recent advances on the newly developed SecA inhibitors that allow the evaluation of their potential as antimicrobial agents, as well as a fundamental understanding of mechanisms of SecA function(s). These SecA inhibitors abrogate the effects of efflux pumps in both Gram-positive and Gram-negative bacteria. We also discuss recent findings that SecA binds to ribosomes and nascent peptides, which suggest other roles of SecA. A model for the multiple roles of SecA is presented.


Asunto(s)
Adenosina Trifosfatasas/antagonistas & inhibidores , Antibacterianos/farmacología , Bacterias/efectos de los fármacos , Bacterias/metabolismo , Proteínas Bacterianas/antagonistas & inhibidores , Canales de Translocación SEC/antagonistas & inhibidores , Adenosina Trifosfatasas/genética , Adenosina Trifosfatasas/metabolismo , Antibacterianos/química , Bacterias/genética , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Canales de Translocación SEC/genética , Canales de Translocación SEC/metabolismo , Proteína SecA
7.
J Sports Med Phys Fitness ; 58(3): 356-365, 2018 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-28222572

RESUMEN

BACKGROUND: Since previous studies have shown that ovariectomy impairs memory and cognition, we investigated whether 8-week treadmill exercise would affect ovariectomy-induced memory deficits and explore the possible mechanisms of physical exercise influencing spatial learning and memory of the ovariectomized rats by detecting the rat's brain free radical metabolism and counting neural nitric oxide synthase (nNOS) expression in marginal division of the striatum (MrD). METHODS: Forty female rats were assigned to one of the following groups: SHAM, SHAM+E, OVX and OVX+E group. The rats of SHAM and OVX group kept normal activities and the SHAM+E and OVX+E group rats undertook an 8-week training with progressively increasing load. Then the cognitive function was evaluated using 8-arm radial maze test. Also, oxidative stress markers in the MrD were also evaluated and the nNOS expression in MrD was detected and analyzed. RESULTS: Results show that ovariectomized rats were impaired in learning and memory and brain SOD (superoxide dismutase), CAT (catalase) activities were dropped and MDA (malondialdehyde) level increased via ovariectomy, nNOS expression in MrD was reduced in comparison with the SHAM group rats. While treadmill exercise significantly alleviated learning and memory decline and prevented oxidative brain damage induced by ovariectomy, nNOS expression in MrD significantly enhanced. CONCLUSIONS: These findings support ovariectomy can impair spatial learning and memory of the rats, the regular treadmill exercise appears to exert a protective effect against ovariectomy, induced spatial memory impairment through inhibition of oxidative stress and up-regulation MrD nNOS expression.


Asunto(s)
Cuerpo Estriado/enzimología , Terapia por Ejercicio , Trastornos de la Memoria/terapia , Memoria , Óxido Nítrico Sintasa de Tipo I/genética , Ovariectomía/efectos adversos , Estrés Oxidativo , Animales , Femenino , Humanos , Malondialdehído/metabolismo , Trastornos de la Memoria/etiología , Trastornos de la Memoria/genética , Trastornos de la Memoria/metabolismo , Óxido Nítrico Sintasa de Tipo I/metabolismo , Condicionamiento Físico Animal , Ratas , Ratas Sprague-Dawley , Superóxido Dismutasa/genética , Superóxido Dismutasa/metabolismo
8.
Zhongguo Zhen Jiu ; 37(7): 741-746, 2017 Jul 12.
Artículo en Chino | MEDLINE | ID: mdl-29231548

RESUMEN

OBJECTIVE: To explore the regulation of acupuncture for transforming growth factor ß1 (TGF-ß1) expression in the lung tissues of bronchial asthmatic rats. METHODS: Forty SPF male SD rats were randomly divided into a blank group, a model group, an acupuncture group and a shallow fast acupuncture group, 10 rats in each group. Asthma model was established in the model, acupuncture, and shallow fast acupuncture groups, and no intervention was applied in the blank and model groups. Before atomization excitation, 20 min acupuncture was applied at "Dazhui" (GV 14) "Feishu" (BL 13) "Fengmen" (BL 12) in the acupuncture group. Acupuncture only into skin without needle retained at the above acupoints was used in the shallow fast acupuncture group before atomization excitation from the day of model established. All the treatment was given 7 times, once the other day. The pathological lunge tissues of rats were observed by HE staining; the protein expression of TGF-ß1 in the lung tissues was examined by immunohistochemical staining and immunofluorescence staining. The TGF-ß1 expressions in bronchoalveolar lavage fluid (BALF) and serum were showed by ELISA. RESULTS: There were changes in the lung tissues in the model group, including mucus plug in the bronchial lumen, irregular bronchial epithelium, thick airway smooth muscle, local break, narrow lumen, a large number of inflammatory cell infiltration. The phenomena in the acupuncture group were improved and those in the shallow fast acupuncture group were not apparently changed compared with those in the model group. The IOD value of TGF-ß1 expression in the model group increased compared with that in the blank group (P<0.05); the positive expression in the acupuncture group was lower than those in the model and shallow fast acupuncture groups (both P<0.05). The contents of TGF-ß1 in BALF and serum of the acupuncture group were lower than those in the model and shallow fast acupuncture groups (all P<0.05). CONCLUSIONS: Acupuncture may improve airway inflammatory response and remolding of asthma by inhibiting TGF-ß1 expression.


Asunto(s)
Terapia por Acupuntura , Asma/metabolismo , Pulmón/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Puntos de Acupuntura , Animales , Líquido del Lavado Bronquioalveolar , Masculino , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley
9.
Zhongguo Zhen Jiu ; 37(4): 406-410, 2017 Apr 12.
Artículo en Chino | MEDLINE | ID: mdl-29231594

RESUMEN

OBJECTIVE: To explore the effects of acupuncture on the expression of protein kinase B (PKB/AKT) in lung tissues of asthma rats. METHODS: Forty SPF male SD rats were randomly divided into a blank group, a model group, an acupuncture group and a blocker group, 10 rats in each one. The rat model of asthma was established by egg albumin stimulation in the model group, acupuncture group and blocker group. Since the establishment of rat model, the rats in the acupuncture group were treated with acupuncture at "Dazhui" (GV 14), "Feishu" (BL 13) and "Fengmen" (BL 12) before atomization; the rats in the blocker group were treated with intervention of blocker LY294002, once every two days, for 7 times. There was no treatment in the blank group and model group. HE staining was applied to observe the morphologic changes of lung tissues; the immunohistochemical method was applied to test the protein expression of AKT in lung tissue. RESULTS: HE staining indicated the infiltration and aggregation of a variety of inflammatory cells around airways, as well as bronchial smooth muscle spasm and confined lumen in the model group; in the acupuncture group and blocker group the inflammatory cells were less and confined lumen was relieved. Compared with the blank group, the protein expression of AKT was higher in the model group (P<0.05); compared with the model group, the protein expression of AKT in the acupuncture group and blocker group was reduced (both P<0.05); the differences between the acupuncture group and blank group, blocker group were not significant (both P>0.05). CONCLUSIONS: Acupuncture could reduce the protein expression of AKT in lung tissue in asthma rats, leading to relieved inflammation reaction and airway remodeling.


Asunto(s)
Terapia por Acupuntura , Asma/metabolismo , Pulmón/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Puntos de Acupuntura , Animales , Masculino , Ratas , Ratas Sprague-Dawley
10.
ChemMedChem ; 11(22): 2511-2521, 2016 11 21.
Artículo en Inglés | MEDLINE | ID: mdl-27753464

RESUMEN

With the widespread emergence of drug resistance, there is an urgent need to search for new antimicrobials, especially those against Gram-negative bacteria. Along this line, the identification of viable targets is a critical first step. The protein translocase SecA is commonly believed to be an excellent target for the development of broad-spectrum antimicrobials. In recent years, we developed three structural classes of SecA inhibitors that have proven to be very effective against Gram-positive bacteria. However, we have not achieved the same level of success against Gram-negative bacteria, despite the potent inhibition of SecA in enzyme assays by the same inhibitors. In this study, we use representative inhibitors as chemical probes to gain an understanding as to why these inhibitors were not effective against Gram-negative bacteria. The results validate our initial postulation that the major difference in effectiveness against Gram-positive and Gram-negative bacteria is in the additional permeability barrier posed by the outer membrane of Gram-negative bacteria. We also found that the expression of efflux pumps, which are responsible for multidrug resistance (MDR), have no effect on the effectiveness of these SecA inhibitors. Identification of an inhibitor-resistant mutant and complementation tests of the plasmids containing secA in a secAts mutant showed that a single secA-azi-9 mutation increased the resistance, providing genetic evidence that SecA is indeed the target of these inhibitors in bacteria. Such results strongly suggest SecA as an excellent target for developing effective antimicrobials against Gram-negative bacteria with the intrinsic ability to overcome MDR. A key future research direction should be the optimization of membrane permeability.


Asunto(s)
Adenosina Trifosfatasas/antagonistas & inhibidores , Antibacterianos/farmacología , Proteínas Bacterianas/antagonistas & inhibidores , Inhibidores Enzimáticos/farmacología , Bacterias Gramnegativas/efectos de los fármacos , Canales de Translocación SEC/antagonistas & inhibidores , Adenosina Trifosfatasas/metabolismo , Antibacterianos/química , Proteínas Bacterianas/metabolismo , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/química , Bacterias Gramnegativas/enzimología , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Canales de Translocación SEC/metabolismo , Proteína SecA , Relación Estructura-Actividad
11.
J Tradit Chin Med ; 36(3): 347-52, 2016 Jun.
Artículo en Chino | MEDLINE | ID: mdl-27468550

RESUMEN

RESULTS: There was a decrease in accessory genital organ weight, plasma testosterone, and sexual behavior, as well as a low number of c-Fos-positive cells and a large nNOS-positive cell area in orchidectomized rats. Administration of the herbal medicine increased accessory genital organ weight, testosterone level, mating behavior, and c-Fos-positive cell number, while it decreased the nNOS-positive cell area in orchidectomized rats. CONCLUSION: An increase of plasma testosterone after administration of "kidney-nourishing" herbal medicine might contribute to the elevated sexual function and activity in orchidectomized rats. In addition, a central nervous system mechanism, such as the functional alteration of NAc, might be involved. Abstract OBJECTIVE: To determine whether the central nervous system is involved in the effect of Chinese herbal medicine on sexual function recovery in orchidectomized rats. METHODS: Orchidectomized rats were administered intragastrically with a decoction of "kidney-nourishing" Chinese herbal medicine once per day for 28 days. Accessory genital organ weight, plasma testosterone, and mating behavior were investigated. The expression of c-Fos and neuronal nitric oxide synthase (nNOS) in neuronal cells in the nucleus accumbens (NAc) was analyzed by immunohistochemistry.


Asunto(s)
Medicamentos Herbarios Chinos/administración & dosificación , Óxido Nítrico Sintasa de Tipo I/genética , Núcleo Accumbens/efectos de los fármacos , Proteínas Proto-Oncogénicas c-fos/genética , Disfunciones Sexuales Fisiológicas/tratamiento farmacológico , Animales , Femenino , Humanos , Masculino , Óxido Nítrico Sintasa de Tipo I/metabolismo , Núcleo Accumbens/metabolismo , Orquiectomía , Proteínas Proto-Oncogénicas c-fos/metabolismo , Ratas , Conducta Sexual , Disfunciones Sexuales Fisiológicas/genética , Disfunciones Sexuales Fisiológicas/metabolismo , Disfunciones Sexuales Fisiológicas/fisiopatología , Testosterona/metabolismo
12.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 36(9): 1124-1127, 2016 Sep.
Artículo en Chino | MEDLINE | ID: mdl-30645855

RESUMEN

Objective To observe the effect of acupuncture on c-fos expression in the lung tissue of asthmatic rats. Methods Totally 70 SPF grade male SD rats were randomly divided into 7 groups, i.e., the blank group (A) , the asthma model group (B) , the blank control group (C) , the asthma-model acupuncture control group (D) , the asthma model acupuncture group ( E) , the asthma model sham-acu- puncture group (F) , the blank acupuncture group (G) , 10 rats in each group. Corresponding interventions were performed to each group. The protein expression of c-fos in lung tissue of rats was detected u- sing immunohistochemistry and Western blot respectively. Results Immunohistochemistry showed negative expression of c-fos protein in Group A, C, G, and E, and weakly positive in Group B, D, and F. Results of Western blot showed the protein expression of c-fos was higher in Group B than in Group A and E (P <0. 01). The protein expression of c-fos was lower in Group E than in Group D and F (P <0. 05, P < 0. 01). Conclusion Acupuncture could reduce the protein expression of c-fos in lung tissue, thus attenu- ating inflammation reaction.


Asunto(s)
Terapia por Acupuntura , Asma , Proteínas Proto-Oncogénicas c-fos , Animales , Asma/metabolismo , Asma/terapia , Pulmón/metabolismo , Masculino , Proteínas Proto-Oncogénicas c-fos/metabolismo , Ratas , Ratas Sprague-Dawley
13.
ChemMedChem ; 11(1): 43-56, 2016 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-26607404

RESUMEN

SecA, a key component of the bacterial Sec-dependent secretion pathway, is an attractive target for the development of new antimicrobial agents. Through a combination of virtual screening and experimental exploration of the surrounding chemical space, we identified a hit bistriazole SecA inhibitor, SCA-21, and studied a series of analogues by systematic dissections of the core scaffold. Evaluation of these analogues allowed us to establish an initial structure-activity relationship in SecA inhibition. The best compounds in this group are potent inhibitors of SecA-dependent protein-conducting channel activity and protein translocation activity at low- to sub-micromolar concentrations. They also have minimal inhibitory concentration (MIC) values against various strains of bacteria that correlate well with the SecA and protein translocation inhibition data. These compounds are effective against methicillin-resistant Staphylococcus aureus strains with various levels of efflux pump activity, indicating the capacity of SecA inhibitors to null the effect of multidrug resistance. Results from studies of drug-affinity-responsive target stability and protein pull-down assays are consistent with SecA as a target for these compounds.


Asunto(s)
Adenosina Trifosfatasas/antagonistas & inhibidores , Proteínas Bacterianas/antagonistas & inhibidores , Diseño de Fármacos , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/farmacología , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Pirimidinas/farmacología , Triazoles/farmacología , Adenosina Trifosfatasas/metabolismo , Proteínas Bacterianas/metabolismo , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/química , Proteínas de Transporte de Membrana/metabolismo , Staphylococcus aureus Resistente a Meticilina/enzimología , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Pirimidinas/química , Canales de Translocación SEC , Proteína SecA , Relación Estructura-Actividad , Triazoles/química
14.
Bioorg Med Chem ; 23(21): 7061-8, 2015 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-26432604

RESUMEN

Due to the emergence and rapid spread of drug resistance in bacteria, there is an urgent need for the development of novel antimicrobials. SecA, a key component of the general bacterial secretion system required for viability and virulence, is an attractive antimicrobial target. Earlier we reported that systematical dissection of a SecA inhibitor, Rose Bengal (RB), led to the development of novel small molecule SecA inhibitors active against Escherichia coli and Bacillus subtilis. In this study, two potent RB analogs were further evaluated for activities against methicillin-resistant Staphylococcus aureus (MRSA) strains and for their mechanism of actions. These analogs showed inhibition on the ATPase activities of S. aureus SecA1 (SaSecA1) and SecA2 (SaSecA2), and inhibition of SaSecA1-dependent protein-conducting channel. Moreover, these inhibitors reduce the secretion of three toxins from S. aureus and exert potent bacteriostatic effects against three MRSA strains. Our best inhibitor SCA-50 showed potent concentration-dependent bactericidal activity against MRSA Mu50 strain and very importantly, 2-60 fold more potent inhibitory effect on MRSA Mu50 than all the commonly used antibiotics including vancomycin, which is considered the last resort option in treating MRSA-related infections. Protein pull down experiments further confirmed SaSecA1 as a target. Deletion or overexpression of NorA and MepA efflux pumps had minimal effect on the antimicrobial activities against S. aureus, indicating that the effects of SecA inhibitors were not affected by the presence of these efflux pumps. Our studies show that these small molecule analogs target SecA functions, have potent antimicrobial activities, reduce the secretion of toxins, and have the ability to overcome the effect efflux pumps, which are responsible for multi-drug resistance. Thus, targeting SecA is an attractive antimicrobial strategy against MRSA.


Asunto(s)
Adenosina Trifosfatasas/antagonistas & inhibidores , Antiinfecciosos/química , Proteínas Bacterianas/antagonistas & inhibidores , Staphylococcus aureus Resistente a Meticilina/enzimología , Rosa Bengala/química , Adenosina Trifosfatasas/metabolismo , Antibacterianos/química , Antibacterianos/farmacología , Antiinfecciosos/farmacología , Proteínas Bacterianas/metabolismo , Sitios de Unión , Evaluación Preclínica de Medicamentos , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Cinética , Luz , Proteínas de Transporte de Membrana/metabolismo , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Simulación del Acoplamiento Molecular , Oxidación-Reducción , Estructura Terciaria de Proteína , Rosa Bengala/farmacología , Canales de Translocación SEC , Proteína SecA , Staphylococcus aureus/efectos de los fármacos
15.
Zhongguo Zhen Jiu ; 34(3): 237-40, 2014 Mar.
Artículo en Chino | MEDLINE | ID: mdl-24843962

RESUMEN

OBJECTIVE: To compare the difference in the efficacy on gait time cycle of ischemic stroke between yin-yang respiratory reinforcing and reducing needling technique (yin-yang needling) and the conventional acupuncture. METHODS: Sixty cases of ischemic stroke were randomized into a conventional acupuncture group and a yin-yang needling group, 30 cases in each one. The basic treatment (the control of blood pressure, blood sugar and blood lipid, the intravenous drops of ginkgo leaf extract and dipyridamole injection and vinpocetine injection) were applied in the two groups. Additionally, in the conventional acupuncture group, the acupoints of the Stomach Meridian of Foot-Yangming [Biguan (ST 31), Liangqiu (ST 34), Zusanli (ST 36), Shangjuxu (ST 37), Xiajuxu (ST 39), etc.] were selected and stimulated with the even needling technique. In the yin-yang needling group, the acupoints of yin meridians such as Zuwuli (LR 10), Xuehai (SP 10), Yinlingquan (SP 9) and Sanyinjiao (SP 6), etc. and the acupoints of yang meridians such as Biguan (ST 31), Liangqiu (ST 34) and Yanglingquan (GB 34), etc. were selected. The reducing manipulation of respiratory reinforcing and reducing technique was applied to the acupoints of yin meridians and the reinforcing manipulation was applied to the acupoints of yang meridians. The kinematics time parameters were determined and compared before and 4 weeks after treatment. RESULTS: After treatment, the differences in the gait cycle, the phase time of standing (%), the phase time of single support (%), the phase time of unilateral sway (%) on the affected (healthy) foot and phase time of double support (%) were significant as compared with those before treatment in the patients of the two groups (all P < 0.05), in which, the gait cycle (1.75 +/- 0.21 vs 2.02 +/- 0.37), the phase time of standing (%) on the affected (healthy) foot [(65.41 +/- 5.20)% vs (68.37 +/- 6.24)%, (70.99 +/- 6.47)% vs (74.51 +/- 5.19)%], the phase time of unilateral sway (%) on the affected (healthy) foot [(36.08 +/- 4.86)% vs (33.65 +/- 2.94)%, (31.04 +/- 3.41)% vs (26.77 +/- 2.67)%] and the phase time of double support (%) [(36.91 +/- 5.10)% vs (41.22 +/- 5.39)%] in the yin-yang needling group were improved much obviously after treatment as compared with those in the conventional acupuncture group. The differences in support phase time (%), single support phase time (%) and sway phase time (%) were significant between the affected limb and healthy limb of the two groups after treatment (all P < 0.05). CONCLUSION: Yin-yang respiratory reinforcing and reducing needling technique effectively improves hemiplegic gait movement cycle and walking function in patients of ischemic stroke, which is superior to the conventional acupuncture treatment.


Asunto(s)
Terapia por Acupuntura , Hipoxia-Isquemia Encefálica/terapia , Accidente Cerebrovascular/terapia , Yin-Yang , Terapia por Acupuntura/instrumentación , Terapia por Acupuntura/métodos , Anciano , Femenino , Marcha , Humanos , Hipoxia-Isquemia Encefálica/fisiopatología , Masculino , Meridianos , Persona de Mediana Edad , Accidente Cerebrovascular/fisiopatología , Factores de Tiempo
16.
Zhongguo Zhen Jiu ; 34(11): 1047-50, 2014 Nov.
Artículo en Chino | MEDLINE | ID: mdl-25675557

RESUMEN

OBJECTIVE: To observe the impact on lower limbs balance function in treatment of yin-yang meridians acupuncture with respiratory reinforcing and reducing manipulation involved in the patients of stroke by applying B-PHY balance function test training system so as to provide the objective evidence in treatment of stroke; with acupuncture. METHODS: One hundred patients were randomized into an observation group and a control group, 50 cases in each one. In the control group, the basic treatment was applied, without other relevant rehabilitation therapies associated. In the observation group, with the basic treatment as the control group's, the therapy of the yin-yang meridians acupuncutre with respiratory reinforcing and reducing manipulation was adopted. On the yin meridians, Zuwuli (LR 10), Xuehai (SP 10), Yinlingquan (SP 9), Sanyinjiao (SP 6) and the others were selected and stimulated with reducing manipulation achieved by the coordination of patient's respiration. On the yang meridians, Biguan (ST 31), Liangqiu (ST 34), Yanglingquan (GB 34) and the others were selected and stimulated with reinforcing manipulation achieved by the coordination of patient's respiration. The treatment was given once a day and for 28 days totally. Before treatment and in 28 days of treatment, B-PHY balance function test training system was used to determine the weight shift track parameters (track length, peripheral square, track length of per unit square, left-right offset and rectangle square), the weight shift track distance parameters [mean of X axle weight shift distance (Mean-X), mean of Y axle weight shift distance (Mean-Y), maximum of X axle weight shift distance (Max-X), maximum of Y axle weight shift distance (Max-Y), weight shift distance (LSKG), weight shift square (SSKG), square ratio of weight shift (LFS)], stability coefficient (SI) and weight distribution coefficient (WDI). RESULTS: After treatment, the differences in the weight shift track parameters, SI and WDI were significant as compared with those before treatment in the patients of the two groups (all P<0.01); while the differences in the weight shift distance parameters in the observation group were improved obviously after treatment as compared with those before treatment (all P<0.01), the differences of Mean-X, Max-Y and LFS in the control group were improved after treatment as compared with those before treatment (all P<0.01). Except SSKG, the improvements after treatment in the rest indices in the observation group were better than those in the control group (all P<0.05). CONCLUSION: The yin-yang meridians acupuncture with respiratry reinforcing and re- ducing manipulation effectively improves the lower limbs balance function in the patients of stroke.


Asunto(s)
Terapia por Acupuntura , Meridianos , Equilibrio Postural , Accidente Cerebrovascular/terapia , Adulto , Anciano , Femenino , Humanos , Extremidad Inferior/fisiopatología , Masculino , Persona de Mediana Edad , Sistema Respiratorio/fisiopatología , Accidente Cerebrovascular/fisiopatología , Resultado del Tratamiento , Yin-Yang
17.
ChemMedChem ; 8(8): 1384-93, 2013 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-23794293

RESUMEN

SecA, a key component of bacterial Sec-dependent secretion pathway, is an attractive target for exploring novel antimicrobials. Rose bengal (RB), a polyhalogenated fluorescein derivative, was found from our previous study as a potent SecA inhibitor. Here we describe the synthesis and structure-activity relationships (SAR) of 23 RB analogues that were designed by systematical dissection of RB. Evaluation of these analogues allowed us to establish an initial SAR in SecA inhibition. The antimicrobial effects of these SecA inhibitors are confirmed in experiments using E. coli and B. subtilis.


Asunto(s)
Adenosina Trifosfatasas/antagonistas & inhibidores , Antiinfecciosos/síntesis química , Proteínas Bacterianas/antagonistas & inhibidores , Diseño de Fármacos , Inhibidores Enzimáticos/síntesis química , Rosa Bengala/química , Adenosina Trifosfatasas/metabolismo , Antiinfecciosos/metabolismo , Antiinfecciosos/farmacología , Bacillus subtilis/efectos de los fármacos , Bacillus subtilis/enzimología , Proteínas Bacterianas/metabolismo , Inhibidores Enzimáticos/metabolismo , Inhibidores Enzimáticos/farmacología , Escherichia coli/efectos de los fármacos , Escherichia coli/enzimología , Proteínas de Transporte de Membrana/metabolismo , Unión Proteica , Rosa Bengala/metabolismo , Rosa Bengala/farmacología , Canales de Translocación SEC , Proteína SecA , Relación Estructura-Actividad
18.
Zhongguo Zhen Jiu ; 33(11): 996-9, 2013 Nov.
Artículo en Chino | MEDLINE | ID: mdl-24494287

RESUMEN

OBJECTIVE: To compare efficacy difference among wrist-ankle needle, body-acupuncture and ibuprofen in the treatment of primary dysmenorrhea. METHODS: Ninety-five cases were randomly divided into a wrist-ankle needle group (32 cases), a body-acupuncture group (31 cases) and an ibuprofen group (32 cases). Acupunc- , ture at Lower 1 and Lower 2 area was applied in the wrist-ankle needle group. Acupuncture at Guanyuan (CV 4) and Sanyinjiao (SP 6) were applied in the body-acupuncture group. Ibuprofen sustained-release capsules were given for oral administration in the ibuprofen group. The treatment began 3 days before menses, once a day, until pain was relieved. One menstrual cycle was taken as a treatment course, continuously for 3 courses and efficacy were observed in three groups. The symptom score of dysmenorrhea and visual analogue scale (VAS) were used to assess pain severity before and after treatment. RESULTS: 1The efficacy differences in three groups were statistically significant (P<0.01), in which the total effective rate was 90. 0% (27/30) in the wrist-ankle needle group, 73.4% (22/30) in the body-acupuncture group and 46. 7% (14/30) in the ibuprofen group. 2 After the treatment, symptom score of dysmenorrhea and VAS were all obviously lower than that before the treatment in three groups (all P<0.01). Compared with ibuprofen group (7.12+/-2.70), after the treatment symptom score of dysmenorrhea in the wrist-ankle needle group (4.00+/-3.40) and body-acupuncture group (5. 53+/-2. 80) was obviously decreased (P<0.01, P<0.05), and VAS in the wrist-ankle needle group was significantly reduced (P<0.05). Compared with body-acupuncture group (5. 53+/-2.80), symptom score of dysmenorrhea in the wrist-ankle needle group (4.00+/- 3. 40) was obviously decreased (P<0. 05). CONCLUSION: The wrist-ankle needle has better effect than body acupuncture and ibuprofen on the treatment of primary dysmenorrhea, which could significantly improve dysmenorrhea symptoms.


Asunto(s)
Terapia por Acupuntura , Dismenorrea/terapia , Puntos de Acupuntura , Adolescente , Adulto , Femenino , Humanos , Dimensión del Dolor , Estudiantes , Resultado del Tratamiento , Adulto Joven
19.
Artículo en Inglés | MEDLINE | ID: mdl-23304218

RESUMEN

Although the beneficial effects of acupuncture in asthma treatment have been well documented, little is known regarding the biological basis of this treatment. Changes in the lung proteome of acupuncture-treated rats with asthma onset were comparatively analyzed using a two-dimensional gel electrophoresis (2DE) and mass-spectrometry- (MS-) based proteomic approach. Acupuncture on specific acupuncture points appeared to improve respiratory function and reduce the total number of leukocytes and eosinophils in bronchoalveolar lavage fluid in OVA-induced asthma onset. Image analysis of 2DE gels revealed 32 differentially expressed acupuncture-specific protein spots in asthma onset; 30 of which were successfully identified as 28 unique proteins using LC-MS/MS. Bioinformatic analyses indicated that these altered proteins are most likely involved in inflammation-related biological functions, and the functional associations of these proteins result in an inflammation signaling pathway. Acupuncture regulates the pathway at different levels by regulating several key nodal proteins, including downregulating of proinflammatory proteins (e.g., S100A8, RAGE, and S100A11) and upregulating of anti-inflammatory proteins (e.g., CC10, ANXA5, and sRAGE). These deregulated inflammation-related proteins may mediate, at least in part, the antiasthmatic effect of acupuncture. Further functional investigation of these acupuncture-specific effector proteins could identify new drug candidates for the prophylaxis and treatment of asthma.

20.
Zhongguo Zhen Jiu ; 31(10): 898-900, 2011 Oct.
Artículo en Chino | MEDLINE | ID: mdl-22043677

RESUMEN

OBJECTIVE: To observe the effect of moxibustion at Sanyinjiao (SP 6) on delivery stage of primipara. METHODS: Sixty cases of primipara were divided into a moxibustion at Sanyinjiao group, a non-acupoint group and a blank group. When the diameter of wormb mouth opened to 2-3 cm, showing that it entered into active stage of uterine contraction, moxibustion at Sanyinjiao (SP 6) for primipara was applied in moxibustion at Sanyinjiao group; moxibustion was applied at 1 cun towards radialis from the region where 2 cun above Kongzui (LU 6) in non-acupoint group, 30 minutes treatment was for both groups. There was no intervention in blank group. After delivery, the time of first,second and third delivery stages and postpartum bleeding 2 hours after delivery were compared among three groups. RESULTS: The active duration of first delivery stage in moxibustion at Sanyinjiao group was significantly shorter than that in the other two groups (P < 0.05, P < 0.01); the duration of the second delivery stage in moxibustion at Sanyinjiao group was significantly shorter than that in the other two groups (both P < 0.05) as well; the postpartum bleeding 2 hours after delivery in moxibustion at Sanyinjiao group was less than other two groups and the difference was statistic significant between moxibustion at Sanyinjiao group and blank group (P < 0.05). CONCLUSION: By moxibustion at Sanyinjiao (SP 6), the active duration of first delivery stage and the duration of second delivery stage are markedly shortened, postpartum bleeding 2 hours after delivery is obviously reduced, and the safety of vaginal delivery is increased.


Asunto(s)
Puntos de Acupuntura , Moxibustión , Hemorragia Posparto/terapia , Adulto , Parto Obstétrico , Femenino , Humanos , Inicio del Trabajo de Parto , Embarazo , Adulto Joven
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...