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1.
Nature ; 595(7867): 409-414, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-34194038

RESUMEN

Social interactions among animals mediate essential behaviours, including mating, nurturing, and defence1,2. The gut microbiota contribute to social activity in mice3,4, but the gut-brain connections that regulate this complex behaviour and its underlying neural basis are unclear5,6. Here we show that the microbiome modulates neuronal activity in specific brain regions of male mice to regulate canonical stress responses and social behaviours. Social deviation in germ-free and antibiotic-treated mice is associated with elevated levels of the stress hormone corticosterone, which is primarily produced by activation of the hypothalamus-pituitary-adrenal (HPA) axis. Adrenalectomy, antagonism of glucocorticoid receptors, or pharmacological inhibition of corticosterone synthesis effectively corrects social deficits following microbiome depletion. Genetic ablation of glucocorticoid receptors in specific brain regions or chemogenetic inactivation of neurons in the paraventricular nucleus of the hypothalamus that produce corticotrophin-releasing hormone (CRH) reverse social impairments in antibiotic-treated mice. Conversely, specific activation of CRH-expressing neurons in the paraventricular nucleus induces social deficits in mice with a normal microbiome. Via microbiome profiling and in vivo selection, we identify a bacterial species, Enterococcus faecalis, that promotes social activity and reduces corticosterone levels in mice following social stress. These studies suggest that specific gut bacteria can restrain the activation of the HPA axis, and show that the microbiome can affect social behaviours through discrete neuronal circuits that mediate stress responses in the brain.


Asunto(s)
Encéfalo/citología , Encéfalo/fisiología , Microbioma Gastrointestinal/fisiología , Neuronas/metabolismo , Conducta Social , Estrés Psicológico , Animales , Corticosterona/sangre , Hormona Liberadora de Corticotropina/metabolismo , Enterococcus faecalis/metabolismo , Vida Libre de Gérmenes , Glucocorticoides/metabolismo , Hipotálamo/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Receptores de Glucocorticoides/metabolismo , Transducción de Señal
2.
J Biomed Sci ; 30(1): 92, 2023 Nov 28.
Artículo en Inglés | MEDLINE | ID: mdl-38012609

RESUMEN

Psychological stress is a global issue that affects at least one-third of the population worldwide and increases the risk of numerous psychiatric disorders. Accumulating evidence suggests that the gut and its inhabiting microbes may regulate stress and stress-associated behavioral abnormalities. Hence, the objective of this review is to explore the causal relationships between the gut microbiota, stress, and behavior. Dysbiosis of the microbiome after stress exposure indicated microbial adaption to stressors. Strikingly, the hyperactivated stress signaling found in microbiota-deficient rodents can be normalized by microbiota-based treatments, suggesting that gut microbiota can actively modify the stress response. Microbiota can regulate stress response via intestinal glucocorticoids or autonomic nervous system. Several studies suggest that gut bacteria are involved in the direct modulation of steroid synthesis and metabolism. This review provides recent discoveries on the pathways by which gut microbes affect stress signaling and brain circuits and ultimately impact the host's complex behavior.


Asunto(s)
Mariposas Diurnas , Microbioma Gastrointestinal , Animales , Humanos
3.
Plant Cell Rep ; 41(8): 1751-1761, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35748890

RESUMEN

KEY MESSAGE: Ketocarotenoids were synthesized successfully in Camelina sativa seeds by genetic modification without using a traditional selection marker genes. This method provided an interesting tool for metabolic engineering of seed crops. Camelina sativa (L.) Crantz is an important oil crop with many excellent agronomic traits. This model oil plant has been exploited to accumulate value-added bioproducts using genetic manipulation that depends on antibiotic- or herbicide-based selection marker genes (SMG), one of the major concerns for genetically modified foods. Here we reported metabolic engineering of C. sativa to synthesize red ketocarotenoids that could serve as a reporter to visualize transgenic events without using a traditional SMG. Overexpression of a non-native ß-carotene ketolase gene coupled with three other carotenogenous genes (phytoene synthase, ß-carotene hydroxylase, and Orange) in C. sativa resulted in production of red seeds that were visibly distinguishable from the normal yellow ones. Constitutive expression of the transgenes led to delayed plant development and seed germination. In contrast, seed-specific transformants demonstrated normal growth and seed germination despite the accumulation of up to 70-fold the level of carotenoids in the seeds compared to the controls, including significant amounts of astaxanthin and keto-lutein. As a result, the transgenic seed oils exhibited much higher antioxidant activity. No significant changes were found in the profiles of fatty acids between transgenic and control seeds. This study provided an interesting tool for metabolic engineering of seed crops without using a disputed SMG.


Asunto(s)
Brassicaceae , Semillas , Brassicaceae/genética , Carotenoides/metabolismo , Ingeniería Metabólica , Plantas Modificadas Genéticamente/genética , Plantas Modificadas Genéticamente/metabolismo , Semillas/metabolismo
4.
J Asian Nat Prod Res ; 21(1): 43-50, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-29082785

RESUMEN

Two series of imperatorin analogs were synthesized based on our previous research and evaluated for their vasodilatation activities on in vitro rat mesenteric artery, basilar artery, and renal artery ring models. Target compounds were characterized by infrared, 1H NMR, and mass spectra. Most derivatives possessed significant vasodilatory activity on the mesenteric artery, and compound 3a exhibited favorable and broad vasodilatation activities on three kinds of rat artery ring models. The pharmacological results indicated that introducing nitrogen-contained ring in side chain or large steric hindrance at the distal end could increase the vasodilatory activity. Further, replacement of oxygen atom (-O-) in the skeleton of furocoumarin derivatives with nitrogen (-NH-) could cause the decrease of vasodilatory activity. The molecular docking also indicated that compound 3a showed a best affinity with α-1C receptor (PDB ID: 3G43). All these results suggested compound 3a would be a potential vasodilatory agent for hypertension.


Asunto(s)
Furocumarinas/síntesis química , Vasodilatadores/síntesis química , Animales , Diseño de Fármacos , Furocumarinas/química , Furocumarinas/farmacología , Arterias Mesentéricas/efectos de los fármacos , Arterias Mesentéricas/fisiología , Simulación del Acoplamiento Molecular , Ratas , Relación Estructura-Actividad , Vasodilatadores/química , Vasodilatadores/farmacología
5.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 41(3): 331-337, 2019 Jun 30.
Artículo en Zh | MEDLINE | ID: mdl-31282326

RESUMEN

Objective To investigate the health care-seeking behaviors of Mosuo and Pumi people.Methods The subjects were enrolled by using the multi-stage stratified random sampling method and surveyed by the self-designed questionnaire.Results To tally 1669 subjects including 1121 Mosuo people and 548 Pumi people completed the survey.When Mosuo and Pumi people suffer from ailments,they preferred to buy drugs in drugstores(47.3% for Mosuo and 46.9% for Pumi),followed by visiting a local township hospital(27.0% for Mosuo and 24.3% for Pumi).When they suffered from severe diseases,they preferred to visit the county/city/state hospital(93.4% for Mosuo and 91.1% for Pumi).The mental disease were mainly treated in the county/city/state hospitals(49.3% for Mosuo and 52.7% for Pumi);notably,39.3% of the Mosuo respondents and 31.5% of the Pumi respondents skipped this question.Conclusion Health education,including awareness-raising activities on mental health,should be enhanced in Mosuo and Pumi people to further improve their health care-seeking behaviors.


Asunto(s)
Aceptación de la Atención de Salud/estadística & datos numéricos , China , Humanos , Encuestas y Cuestionarios
6.
J Physiol ; 594(21): 6267-6286, 2016 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-27338124

RESUMEN

KEY POINTS: The inheritance of two defective alleles of SLC4A4, the gene that encodes the widely-expressed electrogenic sodium bicarbonate cotransporter NBCe1, results in the bicarbonate-wasting disease proximal renal tubular acidosis (pRTA). In the present study, we report the first case of compound-heterozygous inheritance of pRTA (p.Arg510His/p.Gln913Arg) in an individual with low blood pH, blindness and neurological signs that resemble transient ischaemic attacks. We employ fluorescence microscopy on non-polarized (human embryonic kidney) and polarized (Madin-Darby canine kidney) renal cell lines and electrophysiology on Xenopus oocytes to characterize the mutant transporters (R510H and Q913R). Both mutant transporters exhibit enhanced intracellular retention in renal cells, an observation that probably explains the HCO3- transport deficit in the individual. Both mutants retain a close-to-normal per molecule Na+ /HCO3- cotransport activity in Xenopus oocytes, suggesting that they are suitable candidates for folding-correction therapy. However, Q913R expression is uniquely associated with a depolarizing, HCO3- independent, Cl- -conductance in oocytes that could have pathological consequences if expressed in the cells of patients. ABSTRACT: Proximal renal tubular acidosis (pRTA) is a rare, recessively-inherited disease characterized by abnormally acidic blood, blindness, as well as below average height and weight. pRTA is typically associated with homozygous mutation of the solute carrier 4 family gene SLC4A4. SLC4A4 encodes the electrogenic sodium bicarbonate cotransporter NBCe1, a membrane protein that acts to maintain intracellular and plasma pH. We present the first description of a case of compound-heterozygous inheritance of pRTA. The individual has inherited two mutations in NBCe1: p.Arg510His (R510H) and p.Gln913Arg (Q913R), one from each parent. In addition to the usual features of pRTA, the patient exhibits unusual signs, such as muscle spasms and fever. We have recreated these mutant transporters for expression in model systems. We find that both of the mutant proteins exhibit substantial intracellular retention when expressed in mammalian renal cell lines. When expressed in Xenopus oocytes, we find that the R510H and Q913R-mutant NBCe1 molecules exhibit apparently normal Na+ /HCO3- cotransport activity but that Q913R is associated with an unusual HCO3- independent anion-leak. We conclude that a reduced accumulation of NBCe1 protein in the basolateral membrane of proximal-tubule epithelia is the most probable cause of pRTA in this case. We further note that the Q913R-associated anion-leak could itself be pathogenic if expressed in the plasma membrane of mammalian cells, compromising the benefit of strategies aiming to enhance mutant NBCe1 accumulation in the plasma membrane.


Asunto(s)
Acidosis Tubular Renal/genética , Mutación Missense , Simportadores de Sodio-Bicarbonato/metabolismo , Acidosis Tubular Renal/metabolismo , Acidosis Tubular Renal/patología , Adulto , Animales , Bicarbonatos/metabolismo , Membrana Celular/metabolismo , Perros , Células HEK293 , Heterocigoto , Humanos , Células de Riñón Canino Madin Darby , Masculino , Transporte de Proteínas , Simportadores de Sodio-Bicarbonato/genética , Xenopus
7.
Calcif Tissue Int ; 97(4): 336-42, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26135126

RESUMEN

Primary hypertrophic osteoarthropathy (PHO) is a hereditary bone disease characterized by digital clubbing, periostosis, and pachydermia. The HPGD gene encoding 15-prostaglandin dehydrogenase and SLCO2A1 encoding one type of prostaglandin transporter were found to be responsible for PHO. Mutations of either gene would lead to increased level of prostaglandin E2 (PGE2), which might contribute to the constellation of the symptoms. The aim of the study was to analyze the HPGD gene and the clinical characteristics in nine patients with the diagnosis of PHO. Nine patients, (eight males and one female) including two siblings and seven sporadic cases, were enrolled in the study. Clinical features were summarized, and blood and urine samples were collected. Sanger method was used to sequence the HPGD gene to detect mutations. Urinary PGE2 and prostaglandin metabolite (PGE-M) levels for each patient were measured and compared to the healthy controls. A recurrent c.310_311delCT mutation was identified in all patients, of which six were homozygous, two were heterozygous, and one was compound heterozygous with this mutation and a novel heterozygous missense mutation c.488G>A (p.R163H). The levels of PGE2 in urine were much higher than normal in all patients, along with lower PGE-M levels. In conclusion, nine PHO patients were characterized by typical clinical manifestations including digital clubbing, periostosis, and pachydermia. A common mutation and a novel mutation in HPGD gene were identified to be responsible for the disease, and c.310_311delCT mutation is likely to be a hot-spot mutation site for Asian PHO patients.


Asunto(s)
Hidroxiprostaglandina Deshidrogenasas/genética , Osteoartropatía Hipertrófica Primaria/genética , Adolescente , Adulto , Secuencia de Bases , Preescolar , Análisis Mutacional de ADN , Femenino , Humanos , Masculino , Mutación , Adulto Joven
8.
ACS Appl Mater Interfaces ; 16(32): 43064-43071, 2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39092612

RESUMEN

Polymer materials with multiple stimuli-responsive properties have demonstrated many potential and practical applications. By covalently introducing spiropyran (SP1) and spirothiopyran (STP) into the polyurethane backbone, photochromic, mechanochromic, and thermally discolored polymer materials have been prepared. In this work, we report for the first time that white light (violet, blue, and green light) above a certain intensity can activate STP to green color. Based on the above discovery, the polyurethane with SP1 and STP can exhibit reversible three-color changes (brown, green, and purple) in response to four stimuli: ultraviolet irradiation, white light irradiation, mechanical stress, and heat. The color-changing polymer materials have high color contrast and excellent reversibility, and can be used for reversible writing, anticounterfeiting and information encryption, etc.

9.
Eur J Pharmacol ; 980: 176871, 2024 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-39117263

RESUMEN

Non-small cell lung cancer (NSCLC) poses a global health threat, and epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) such as gefitinib, afatinib, and osimertinib have achieved significant success in clinical treatment. However, the emergence of resistance limits the long-term efficacy of these treatments, necessitating urgent exploration of novel EGFR-TKIs. This review provides an in-depth summary and exploration of the resistance mechanisms associated with EGFR-TKIs, with a specific focus on representative drugs like gefitinib, afatinib, and osimertinib. Additionally, the review introduces a therapeutic strategy involving the combination of Chinese herbal medicines (CHMs) and chemotherapy drugs, highlighting the potential role of CHMs in overcoming NSCLC resistance. Through systematic analysis, we elucidate the primary resistance mechanisms of EGFR-TKIs in NSCLC treatment, emphasizing CHMs as potential treatment medicines and providing a fresh perspective for the development of next-generation EGFR-TKIs. This comprehensive review aims to guide the application of CHMs in combination therapy for NSCLC management, fostering the development of more effective and comprehensive treatment modalities to ultimately enhance patient outcomes.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Medicamentos Herbarios Chinos , Receptores ErbB , Neoplasias Pulmonares , Inhibidores de Proteínas Quinasas , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Receptores ErbB/antagonistas & inhibidores , Medicamentos Herbarios Chinos/uso terapéutico , Medicamentos Herbarios Chinos/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/farmacología , Resistencia a Antineoplásicos/efectos de los fármacos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Animales , Antineoplásicos/uso terapéutico , Antineoplásicos/farmacología
10.
Crit Rev Eukaryot Gene Expr ; 23(3): 275-82, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23879543

RESUMEN

Overexpression of ECHS1 occurs in different cancers, including hepatocellular carcinoma (HCC). ECHS1 is also reported to have an oncogenic activity in various human cancers. This study investigated the effect of ECHS1 knockdown on the regulation of HCC growth. ECHS1 shRNA suppressed the expression of ECHS1 protein in HepG2 cells compared to the negative control vector-transfected HCC cells. ECHS1 knockdown also reduced HCC cell viability and enhanced cisplatin-induced apoptosis in HCC cells. Akt activation and the expression of various cell cycle-related genes were inhibited following ECHS1 knockdown. ECHS1 shRNA suppressed hepatocellular carcinoma growth in tumor xenograft mice. These data demonstrate that ECHS1 may play a role in HCC progression, suggesting that inhibition of ECHS1 expression using ECHS1 shRNA should be further evaluated as a novel target for the control of HCC.


Asunto(s)
Proliferación Celular , Enoil-CoA Hidratasa/genética , Proteínas Proto-Oncogénicas c-akt/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-akt/genética , Animales , Apoptosis , Carcinoma Hepatocelular/genética , Movimiento Celular , Supervivencia Celular , Células Cultivadas , Cisplatino , Enoil-CoA Hidratasa/metabolismo , Regulación Neoplásica de la Expresión Génica , Técnicas de Silenciamiento del Gen , Células Hep G2 , Humanos , Etiquetado Corte-Fin in Situ , Neoplasias Hepáticas/genética , Masculino , Ratones , Ratones Desnudos , Proteínas Proto-Oncogénicas c-akt/metabolismo , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismo
11.
J Ethnopharmacol ; 311: 116409, 2023 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-37003401

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: The rhizome of Curcuma wenyujin Y.H. Chen & C. Ling, also known as Wen-E-Zhu, has been used for cancer treatment since ancient times, with roots dating back to the Song Dynasty. Elemene (EE), a sesquiterpene extract with potent anticancer properties, is extracted from Wen-E-Zhu, with ß-elemene (BE) being its main active compound, along with trace amounts of ß-caryophyllene (BC), γ-elemene and δ-elemene isomers. EE has demonstrated broad-spectrum anti-cancer effects and is commonly used in clinical treatments for various types of malignant cancers, including lung cancer. Studies have shown that EE can arrest the cell cycle, inhibit cancer cell proliferation, and induce apoptosis and autophagy. However, the exact mechanism of its anti-lung cancer activity remains unclear and requires further research and investigation. AIM OF THE STUDY: In this study, the possible mechanism of EE and its main active components, BE and BC, against lung adenocarcinoma was investigated by using A549 and PC9 cell lines. MATERIALS AND METHODS: The subcutaneous tumor model of nude mice was constructed to evaluate the efficacy of EE in vivo, then the in vitro half-inhibitory concentration (IC50) of EE and its main active components, BE and BC, on A549 and PC9 cells at different concentrations were determined by CCK-8. Flow cytometry was used to detect the apoptosis and cycle of A549 and PC9 cells treated with different concentrations of BE and BC for 24 h. Non-targeted metabolomics analysis was performed on A549 cells to explore potential target pathways, which were subsequently verified through kit detection and western blot analysis. RESULTS: Injection of EE in A549 tumor-bearing mice effectively suppressed cancer growth in vivo. The IC50 of EE and its main active components, BE and BC, was around 60 µg/mL. Flow cytometry analysis showed that BE and BC blocked the G2/M and S phases of lung adenocarcinoma cells and induced apoptosis, leading to a significant reduction in mitochondrial membrane potential (MMP). Results from non-targeted metabolomics analysis indicated that the glutathione metabolism pathway in A549 cells was altered after treatment with the active components. Kit detection revealed a decrease in glutathione (GSH) levels and an increase in the levels of oxidized glutathione (GSSG) and reactive oxygen (ROS). Supplementation of GSH reduced the inhibitory activity of the active components on lung cancer and also decreased the ROS content of cells. Analysis of glutathione synthesis-related proteins showed a decrease in the expression of glutaminase, cystine/glutamate reverse transporter (SLC7A11), and glutathione synthase (GS), while the expression of glutamate cysteine ligase modified subunit (GCLM) was increased. In the apoptosis-related pathway, Bax protein and cleaved caspase-9/caspase-9 ratio were up-regulated and Bcl-2 protein was down-regulated. CONCLUSIONS: EE, BE, and BC showed significant inhibitory effects on the growth of lung adenocarcinoma cells, and the mechanism of action was linked to the glutathione system. By down-regulating the expression of proteins related to GSH synthesis, EE and its main active components BE and BC disrupted the cellular redox system and thereby promoted cell apoptosis.


Asunto(s)
Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Sesquiterpenos , Animales , Ratones , Caspasa 9/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Ratones Desnudos , Adenocarcinoma del Pulmón/tratamiento farmacológico , Neoplasias Pulmonares/patología , Sesquiterpenos/farmacología , Sesquiterpenos/uso terapéutico , Apoptosis , Glutatión/metabolismo , Proliferación Celular , Línea Celular Tumoral
12.
J Diabetes Complications ; 37(10): 108598, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37716256

RESUMEN

AIMS: To examine the risk association of insomnia with incident chronic cognitive impairment in older adults with type 2 diabetes mellitus (T2D). METHODS: Between July 2010 and June 2015, patients with T2D aged ≥60 years enrolled in the Hong Kong Diabetes Register completed the Insomnia Severity Index (ISI) questionnaire. Patients were considered having insomnia if they had ISI score > 14. We prospectively followed up the cohort and censored outcome through reviewing diagnoses and clinical notes entered by attending physicians in electronic medical record to identify incident cases of mild cognitive impairment and dementia. RESULTS: After excluding shift workers and those with established chronic cognitive impairment at baseline, we included 986 patients with T2D in this study (58.3 % men, mean age ± standard deviation: 62.5 ± 2.6 years, disease duration of diabetes: 10.7 ± 8.2 years, HbA1c: 7.4 ± 1.3 %, insulin users: 28.7 %, insomnia: 9.1 %). After a median follow-up of 7.6 (interquartile range = 2.0) years, 41 (4.2 %) developed chronic cognitive impairment. Using Cox regression analysis, insomnia (hazard ratio, HR 2.909, p = 0.012) and HbA1c ≥ 7 % (HR 2.300, p = 0.038) were positively associated with incident chronic cognitive impairment while insulin use (HR 0.309, p = 0.028) showed negative association. CONCLUSIONS: Insomnia, suboptimal glycemic control and non-insulin use are independent risk factors for incident chronic cognitive impairment in older adults with T2D.


Asunto(s)
Disfunción Cognitiva , Diabetes Mellitus Tipo 2 , Trastornos del Inicio y del Mantenimiento del Sueño , Masculino , Humanos , Anciano , Femenino , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Estudios Prospectivos , Hemoglobina Glucada , Hong Kong/epidemiología , Trastornos del Inicio y del Mantenimiento del Sueño/complicaciones , Trastornos del Inicio y del Mantenimiento del Sueño/epidemiología , Factores de Riesgo , Disfunción Cognitiva/complicaciones , Disfunción Cognitiva/epidemiología , Insulina
13.
J Cardiovasc Pharmacol ; 59(1): 37-48, 2012 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-21921806

RESUMEN

Modulation of the inward rectifier K current (IK1) has profound effect on cardiac excitability and underlies new antiarrhythmic strategies. However, IK1-specific pharmacological tools, especially the selective IK1 agonists, are still lacking in the market. Zacopride, a gastrointestinal prokinetic drug, was found to be a selective IK1 channel agonist. By using the whole-cell patch clamp technique, it was found that zacopride (0.1-10 µmole/L) dose dependently enhanced the IK1 current in isolated rat cardiomyocytes, had no effects on other ion channels, transporters, or pumps. At the same dosage range, zacopride hyperpolarized the resting potential and shortened the action potential duration. When applied at the optimal dose of 1.0 µmole/L, zacopride could prevent or eliminate aconitine induced after depolarization and triggered activity in isolated cardiomyocytes. In a rat model of aconitine-induced arrhythmias both ex vivo and in vivo, zacopride (1.0 µmole/L or 25 µg/kg, respectively) treatment apparently protected the heart from ventricular tachyarrhythmias, which compares favorably with 7.5 mg/kg of lidocaine, a classical aconitine antidote. In conclusion, zacopride was found to be a selective IK1 agonist, and agonizing IK1 could prevent or eliminate aconitine-induced arrhythmias in the rat.


Asunto(s)
Antiarrítmicos/uso terapéutico , Benzamidas/uso terapéutico , Compuestos Bicíclicos Heterocíclicos con Puentes/uso terapéutico , Canales de Potasio de Rectificación Interna/agonistas , Taquicardia Ventricular/tratamiento farmacológico , Aconitina/farmacología , Animales , Antiarrítmicos/administración & dosificación , Antiarrítmicos/farmacología , Benzamidas/administración & dosificación , Benzamidas/farmacología , Compuestos Bicíclicos Heterocíclicos con Puentes/administración & dosificación , Compuestos Bicíclicos Heterocíclicos con Puentes/farmacología , Células Cultivadas , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Electrocardiografía , Cobayas , Masculino , Potenciales de la Membrana/efectos de los fármacos , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Técnicas de Placa-Clamp , Ratas , Ratas Sprague-Dawley , Taquicardia Ventricular/metabolismo
14.
Diabetes Metab Syndr ; 16(6): 102510, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35613489

RESUMEN

BACKGROUND AND AIMS: Controlling glycemic levels is crucial for patients with diabetes mellitus to improve their disease management and health outcomes. Beyond lifestyle modification and pharmacotherapy, some supplements have been shown to lower blood glucose as well as mitigate diabetic complications. METHODS: Information was primarily gathered by employing various PubMed scholarly articles for real-world examples in addition to data extraction from supplementary manuscripts. Only original human trials were used, and those published within the past two decades were primarily chosen. However, background information may contains review articles. RESULTS: Some non-herbal supplements have been suggested to lower fasting blood glucose, postprandial glucose, glycated glucose (HbA1c), lipid profiles, oxidative stress, and inflammation, as well as improving body composition, insulin sensitivity, blood pressure, and nephropathy. CONCLUSION: This review discusses ten non-herbal supplements that have been reported to have beneficial effects among different types of patients with diabetes as well as potential future clinical application. However, more long-term studies with a larger amount and more diverse participants need to be conducted for a robust conclusion. Also, mechanisms of action of antidiabetic effects are poorly understood and need further research.


Asunto(s)
Diabetes Mellitus Tipo 2 , Resistencia a la Insulina , Glucemia , Hemoglobina Glucada , Humanos , Hipoglucemiantes/uso terapéutico
15.
Brain Behav ; 12(4): e2545, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35315239

RESUMEN

BACKGROUND: Direct moxibustion (DM) is reported to be useful for cervical spondylotic radiculopathy (CSR), but the analgesic mechanism remains unknown. Autophagy plays a protective role in neuronal apoptosis, Act A/Smads signaling pathway has been confirmed to be associated with the activation of autophagy. The study aimed to explore the effect of DM on autophagy in rats with CSR and the involvement of Act A/Smads signaling pathway. METHODS: Rats were randomly divided into Sham, CSR, CSR + DM, CSR + DM + 3-MA (PI3K inhibitor), and CSR + DM + SB (Act A inhibitor) group. Three days after establishment of CSR model with a fish line inserted under the axilla of the nerve roots, DM at Dazhui (GV14) was performed six times once for seven consecutive days. Western blot and immunofluorescence staining were used to observe the expression of the neuronal autophagy molecule LC3II/I, Atg7, and Act A/Smads signaling molecule Act A, p-Smad2, and p-Smad3. Bcl-2/Bax mRNA expression was measured by real time PCR. RESULTS: DM improved the pain threshold and motor function of CSR rats and promoted the expression of Act A, p-Smad2, p-Smad3, LC3II/I, and Atg7 in the entrapped-nerve root spinal dorsal horn. DM reduced the expression of Bax mRNA and decreased the number of apoptotic neurons. 3-MA and Act A inhibitor SB suppressed the expression of above-mentioned proteins and reduced the protective effect of DM on apoptotic neurons. CONCLUSION: DM exerts analgesic effects by regulating the autophagy to reduce cell apoptosis and repair nerve injury, and this feature may be related to the Act A/Smads signaling pathway.


Asunto(s)
Moxibustión , Radiculopatía , Espondilosis , Animales , Autofagia , Fosfatidilinositol 3-Quinasas , ARN Mensajero , Radiculopatía/genética , Radiculopatía/terapia , Ratas , Transducción de Señal , Proteína X Asociada a bcl-2
16.
Zhen Ci Yan Jiu ; 47(3): 244-9, 2022 Mar 25.
Artículo en Zh | MEDLINE | ID: mdl-35319842

RESUMEN

OBJECTIVE: To observe the effect of mild moxibustion (Moxi) at "Dazhui" (GV14) on neuropathic pain, expression of autophagy and apoptosis factor LC3 and Bax proteins and mRNAs in the spinal cord tissue in rats with cervical spondylotic radiculopathy (CSR), so as to explore its underlying mechanism underlying relief of CSR-induced pain. METHODS: Forty rats (half male half female) were randomly divided into blank control, model, Moxi, Moxi+autophagy inhibitor 3-methyladenine (3-MA, Moxi+3-MA) groups, with 10 rats in each group. The CSR model was established by loose ligature of the local cervical nerve roots. Three days after modeling, mild Moxi was applied to GV14 for 10 min, once daily for 7 days. Rats of the Moxi+3-MA group received intraperitoneal injection of 3-MA(1 mL, 15 mg/kg+ saline) before Moxi, once daily for 7 consecutive days. Rats of the model and Moxi groups were also given normal saline (i.p., 1 mL), once daily for 7 days. The gait behavior score (1-3 points) was scaled according to the rats' pain reaction and foot paw contracture produced walking disorder and the mechanical pain threshold (MPT) was detected before and after the treatment. The expression of spinal cord LC3 and Bax proteins and mRNAs were detected by immunohistochemistry and quantitative RT-PCR, respectively. RESULTS: Compared with the blank control group, the gait disorder score, and percentage of Bax positive cells and expression of Bax mRNA were significantly increased (P<0.01, P<0.05), and MPT was markedly decreased in the model group (P<0.01). After the treatment, the gait disorder score, percentage of Bax positive cells and Bax mRNA expression were significantly down-regulated (P<0.01, P<0.05), while the MPT and percentage of LC3 positive cells and LC3 mRNA expression were considerably increased (P<0.01, P<0.05) in both Moxi and Moxi+3-MA groups. The therapeutic effects of mild Moxi were remarkably superior to those of Moxi+3-MA in downregulating gait disorder score, Bax positive cell percentage and Bax mRNA expression, and in up-regulating MPT, LC3 positive cell percentage and LC3 mRNA expression (P<0.05), suggesting a reduction of the function of mild Moxi after administration of 3-MA. CONCLUSION: Mild Moxi at GV14 can relieve neuropathic pain in CSR rats, which may be related to its functions in up-regulating LC3 autophagy, thereby inhibiting the expression of Bax pro-apoptotic protein in spinal cord to reduce apoptosis and to repair nerve injury.


Asunto(s)
Moxibustión , Neuralgia , Radiculopatía , Animales , Femenino , Masculino , Proteínas Asociadas a Microtúbulos/genética , Radiculopatía/genética , Radiculopatía/terapia , Ratas , Ratas Sprague-Dawley , Médula Espinal , Proteína X Asociada a bcl-2/genética
17.
Zhongguo Zhen Jiu ; 42(5): 533-9, 2022 May 12.
Artículo en Zh | MEDLINE | ID: mdl-35543944

RESUMEN

OBJECTIVE: To observe the effect of wheat-grain moxibustion at "Dazhui" (GV 14) on the expressions of Beclin-1 and GRP78 in spinal dorsal horn in rats with cervical spondylotic radiculopathy (CSR), and to explore the possible analgesic mechanism of wheat-grain moxibustion for CSR. METHODS: A total of 48 SD rats were randomly divided into a sham operation group, a model group, a wheat-grain moxibustion group and a wheat-grain moxibustion+3-MA group, 12 rats in each group. The CSR model was prepared by spinal cord insertion method. Three days after modeling, the rats in the model group were intraperitoneally injected with 1 mL of 0.9% sodium chloride solution; the rats in the wheat-grain moxibustion group were treated with wheat-grain moxibustion at "Dazhui" (GV 14, 6 cones per time) on the basis of the model group; the rats in the wheat-grain moxibustion+3-MA group were intraperitoneally injected with 3-MA solution and wheat-grain moxibustion at "Dazhui" (GV 14, 6 cones per time). The three groups were intervened for 7 days, once a day. The gait score and mechanical pain threshold were observed before treatment and 7 days into treatment; after the treatment, the expressions of mRNA and protein of Beclin-1 in spinal dorsal horn were detected by real-time fluorescence quantitative PCR and immunohistochemistry; the expression of GRP78 protein in spinal dorsal horn was detected by Western blot method; the autophagosomes and ultrastructure in spinal dorsal horn neurons were observed by electron microscope. RESULTS: After the treatment, compared with the sham operation group, in the model group, the gait score was increased and the mechanical pain threshold was decreased (P<0.01), and the expression of GRP78 protein in spinal dorsal horn was increased (P<0.01). Compared with the model group and the wheat-grain moxibustion+3-MA group, in the wheat-grain moxibustion group, the gait score was decreased and mechanical pain threshold was increased (P<0.01), and the expression of GRP78 protein in spinal dorsal horn was decreased, and the expressions of mRNA and protein of Beclin-1 were increased (P<0.01). Under electron microscope, the ultrastructure of spinal dorsal horn neurons in the wheat-grain moxibustion group was not significantly damaged, and its structure was basically close to normal, and the number of autophagosomes was more than the other three groups. CONCLUSION: Wheat-grain moxibustion at "Dazhui" (GV 14) has analgesic effect on CSR rats. The mechanism may be related to moderately up-regulate the expression of Beclin-1, enhance autophagy and reduce endoplasmic reticulum stress.


Asunto(s)
Moxibustión , Radiculopatía , Espondilosis , Animales , Beclina-1/genética , Chaperón BiP del Retículo Endoplásmico , ARN Mensajero , Radiculopatía/genética , Radiculopatía/terapia , Ratas , Ratas Sprague-Dawley , Médula Espinal , Asta Dorsal de la Médula Espinal , Triticum/genética
18.
Neuropharmacology ; 214: 109140, 2022 08 15.
Artículo en Inglés | MEDLINE | ID: mdl-35613660

RESUMEN

Anxiety is characterized by feelings of tension and worry even in the absence of threatening stimulus. Pathological condition of anxiety elicits defensive behavior and aversive reaction ultimately impacting individuals and society. The gut microbiota has been shown to contribute to the modulation of anxiety-like behavior in rodents through the gut-brain axis. Several studies observed that germ-free (GF) and the broad spectrum of antibiotic cocktail (ABX)-treated rodents display lowered anxiety-like behavior. We speculate that gut microbial short-chain fatty acids (SCFA) modulate the innate anxiety response. Herein, we administered SCFA in the drinking water in adult mice treated with ABX to deplete the microbiota and tested their anxiety-like behavior. To further augment the innate fear response, we enhanced the aversive stimulus of the anxiety-like behavior tests. Strikingly, we found that the anxiety-like behavior in ABX mice was not altered when enhanced aversive stimulus, while control and ABX mice supplemented with SCFA displayed increased anxiety-like behavior. Vagus nerve serves as a promising signaling pathway in the gut-brain axis. We determined the role of vagus nerve by subdiaphragmatic vagotomy (SDV) in ABX mice supplemented with SCFA. We found that the restored anxiety-like behavior in ABX mice by SCFA was unaffected by SDV. These findings suggest that gut microbiota can regulate anxiety-like behavior through their fermentation products SCFA.


Asunto(s)
Microbioma Gastrointestinal , Microbiota , Animales , Ansiedad/tratamiento farmacológico , Trastornos de Ansiedad , Ácidos Grasos Volátiles/metabolismo , Ratones , Ratones Endogámicos C57BL
19.
Zhongguo Zhen Jiu ; 41(12): 1333-7, 2021 Dec 12.
Artículo en Zh | MEDLINE | ID: mdl-34936270

RESUMEN

OBJECTIVE: To compare the clinical effect of acupuncture combined with wheat-grain moxibustion and oral sertraline hydrochloride dispersible tablets in the treatment of mild to moderate postpartum depression. METHODS: Sixty patients with mild to moderate postpartum depression were randomly divided into an observation group and a control group, 30 cases in each group. Both groups were treated with psychotherapy. The control group was treated with oral sertraline hydrochloride dispersible tablets, 50 mg each time, once a day; the observation group was treated with acupuncture at Qihai (CV 6), Zusanli (ST 36), Xuehai (SP 10), Hegu (LI 4), Sanyinjiao (SP 6), Taixi (KI 3), etc. combined with wheat-grain moxibustion at Xinshu (BL 15), Pishu (BL 20), Ganshu (BL 18) and Shenshu (BL 23), once every other day, 3 times a week. Both groups were treated for 4 weeks as a course, with 2 consecutive courses of treatment. Before and after treatment and follow-up of 3 months after the end of treatment, the Hamilton depression scale (HAMD), Edinburgh postnatal depression scale (EPDS) and World Health Organization quality of life-BREF (WHOQOL-BREF) score of the two groups were compared, and the clinical effect was assessed. RESULTS: After treatment and during follow-up, the HAMD and EPDS scores of the two groups were lower than before treatment (P<0.05), and the WHOQOL-BREF scores of the two groups were higher than before treatment (P<0.05). In the control group, the scores of HAMD and EPDS during follow-up were higher than after treatment (P<0.05), and the score of WHOQOL-BREF during follow-up was lower than after treatment (P<0.05). After treatment and during follow-up, the HAMD and EPDS scores of the observation group were lower than those of the control group (P<0.05), and the WHOQOL-BREF score of the observation group was higher than that of the control group (P<0.05). The total effective rate of the observation group was 93.3% (28/30), which was higher than 86.7% (26/30) of the control group (P<0.05). CONCLUSION: Acupuncture combined with wheat-grain moxibustion can improve the depressive symptoms of patients with mild to moderate postpartum depression and improve their quality of life, and the clinical effect is more lasting and stable than oral sertraline hydrochloride dispersible tablets.


Asunto(s)
Terapia por Acupuntura , Depresión Posparto , Moxibustión , Puntos de Acupuntura , Depresión Posparto/terapia , Femenino , Humanos , Calidad de Vida , Resultado del Tratamiento , Triticum
20.
Sheng Li Xue Bao ; 62(5): 407-14, 2010 Oct 25.
Artículo en Inglés | MEDLINE | ID: mdl-20945042

RESUMEN

Considering that α-1 repeat region may be involved in the ion binding and translocation of Na(+)-Ca(2+) exchanger (NCX), it is possible that the antibodies against NCX α-1 repeat may have a crucial action on NCX activity. The aim of the present study is to investigate the effect of antibody against α-1 repeat (117-137), designated as α-1(117-137), on NCX activity. The antibody against the synthesized α-1(117-137) was prepared and affinity-purified. Whole-cell patch clamp technique was used to study the change of Na(+)-Ca(2+) exchange current (I(Na/Ca)) in adult rat cardiomyocytes. To evaluate the functional specificity of this antibody, its effects on L-type Ca(2+) current (I(Ca,L)), voltage-gated Na(+) current (I(Na)) and delayed rectifier K(+) current (I(K)) were also observed. The amino acid sequences of α-1(117-137) in NCX and residues 1 076-1 096 within L-type Ca(2+) channel were compared using EMBOSS Pairwise Alignment Algorithms. The results showed that outward and inward I(Na/Ca) were decreased by the antibody against α-1(117-137) dose-dependently in the concentration range from 10 to 160 nmol/L, with IC(50) values of 18.9 nmol/L and 22.4 nmol/L, respectively. Meanwhile, the antibody also decreased I(Ca,L) in a concentration-dependent manner with IC(50) of 22.7 nmol/L. No obvious effects of the antibody on I(Na) and I(K) were observed. Moreover, comparison of the amino acid sequences showed there was 23.8% sequence similarity between NCX α-1(117-137) and residues 1 076-1 096 within L-type Ca(2+) channel. These results suggest that antibody against α-1(117-137) is a blocking antibody to NCX and can also decrease I(Ca,L) in a concentration-dependent manner, while it does not have obvious effects on I(Na) and I(K).


Asunto(s)
Anticuerpos Bloqueadores/farmacología , Bloqueadores de los Canales de Calcio/farmacología , Canales de Calcio Tipo L , Miocitos Cardíacos/metabolismo , Intercambiador de Sodio-Calcio/antagonistas & inhibidores , Secuencia de Aminoácidos , Animales , Anticuerpos Bloqueadores/metabolismo , Canales de Calcio Tipo L/genética , Canales de Calcio Tipo L/inmunología , Canales de Calcio Tipo L/metabolismo , Cobayas , Potenciales de la Membrana , Datos de Secuencia Molecular , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/fisiología , Técnicas de Placa-Clamp , Ratas , Ratas Wistar , Intercambiador de Sodio-Calcio/genética , Intercambiador de Sodio-Calcio/inmunología
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