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1.
Chin J Nat Med ; 22(1): 62-74, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38278560

RESUMEN

Pathological vascular remodeling is a hallmark of various vascular diseases. Previous research has established the significance of andrographolide in maintaining gastric vascular homeostasis and its pivotal role in modulating endothelial barrier dysfunction, which leads to pathological vascular remodeling. Potassium dehydroandrographolide succinate (PDA), a derivative of andrographolide, has been clinically utilized in the treatment of inflammatory diseases precipitated by viral infections. This study investigates the potential of PDA in regulating pathological vascular remodeling. The effect of PDA on vascular remodeling was assessed through the complete ligation of the carotid artery in C57BL/6 mice. Experimental approaches, including rat aortic primary smooth muscle cell culture, flow cytometry, bromodeoxyuridine (BrdU) incorporation assay, Boyden chamber cell migration assay, spheroid sprouting assay, and Matrigel-based tube formation assay, were employed to evaluate the influence of PDA on the proliferation and motility of smooth muscle cells (SMCs). Molecular docking simulations and co-immunoprecipitation assays were conducted to examine protein interactions. The results revealed that PDA exacerbates vascular injury-induced pathological remodeling, as evidenced by enhanced neointima formation. PDA treatment significantly increased the proliferation and migration of SMCs. Further mechanistic studies disclosed that PDA upregulated myeloid differentiation factor 88 (MyD88) expression in SMCs and interacted with T-cadherin (CDH13). This interaction augmented proliferation, migration, and extracellular matrix deposition, culminating in pathological vascular remodeling. Our findings underscore the critical role of PDA in the regulation of pathological vascular remodeling, mediated through the MyD88/CDH13 signaling pathway.


Asunto(s)
Cadherinas , Traumatismos de las Arterias Carótidas , Diterpenos , Lesiones del Sistema Vascular , Ratones , Ratas , Animales , Factor 88 de Diferenciación Mieloide/genética , Factor 88 de Diferenciación Mieloide/metabolismo , Remodelación Vascular , Proliferación Celular , Lesiones del Sistema Vascular/metabolismo , Lesiones del Sistema Vascular/patología , Traumatismos de las Arterias Carótidas/patología , Simulación del Acoplamiento Molecular , Músculo Liso Vascular , Movimiento Celular , Ratones Endogámicos C57BL , Transducción de Señal , Succinatos/metabolismo , Succinatos/farmacología , Potasio/metabolismo , Potasio/farmacología , Células Cultivadas
2.
Sci Rep ; 13(1): 21325, 2023 12 03.
Artículo en Inglés | MEDLINE | ID: mdl-38044365

RESUMEN

Arteriovenous fistula (AVF) is the first choice of vascular access in hemodialysis (HD) patients. However, the correlations between patient factors and the arteriovenous fistula patency remain unclear. Therefore, our study investigates the risk factors associated with AVF dysfunction in HD patients. A total of 233 end-stage renal disease (ESDR) patients who met the study inclusion criteria in the Nephrology Department of Hunan Provincial People's Hospital between December 2020 and June 2022 were included in this study. The baseline demographic, clinical and laboratory parameters were collected at the time of AVF creation and analyzed. Of the 233 ESRD patients, 146 (62.7%) were male and the mean age was 56.11 ± 12.14 (21-82) years. The patients were followed for a median time of 14 months. Kaplan-Meier analysis showed a 6-, 12- and 24-month post-placement survival of 87.1%, 82.8% and 80.7%, respectively. Univariate Cox regression analysis revealed weight (HR, 1.03; P = 0.03) as a predictor for the loss of vascular access functionality. In addition, multivariate Cox regression analysis further demonstrated that sex (HR, 3.41; P = 0.03), weight (HR 1.08; P < 0.01) and phosphorus level (HR: 3.03; P = 0.01) are independent risk factors for AVF dysfunction. AVF dysfunction is highly associated with several risk factors including weight, phosphorus level, and sex. Positive intervention strategies targeting these potential factors, such as weight loss or oral phosphate binders could improve the long-term success of AVF.


Asunto(s)
Fístula Arteriovenosa , Derivación Arteriovenosa Quirúrgica , Fallo Renal Crónico , Humanos , Masculino , Adulto , Persona de Mediana Edad , Anciano , Femenino , Estudios Retrospectivos , Grado de Desobstrucción Vascular , Derivación Arteriovenosa Quirúrgica/efectos adversos , Diálisis Renal/efectos adversos , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/terapia , Factores de Riesgo , Fístula Arteriovenosa/etiología , Fósforo , Resultado del Tratamiento
3.
RSC Adv ; 13(46): 32778-32785, 2023 Oct 31.
Artículo en Inglés | MEDLINE | ID: mdl-37942447

RESUMEN

Danggui Buxue Decoction (DBD), consisting of Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao (Huangqi, HQ) and Angelica sinensis (Oliv.) Diels (Danggui, DG), is a traditional Chinese medicine (TCM) formula with the function of tonifying Qi and promoting blood. In this study, ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) was used to comprehensively identify the chemical constituents in DBD and those entering into the rat serum after gastric perfusion. A combination of the UNIFI platform and Global Natural Product Social molecular networking (GNPS) was used to analyze the chemical composition of DBD. As a result, 207 compounds were unambiguously or tentatively identified including 60 flavonoids, 38 saponins, 35 organic acids, 26 phthalides, 12 phenylpropanoids, 11 amino acids and 25 others. Furthermore, a total of 80 compounds, including 29 prototype components and 51 exogenous metabolites, were detected in the serum of rats. Phase I reactions (oxidation, reduction, and hydration), phase II reactions (methylation, sulfation, and glucuronidation), and their combinations were the main metabolic pathways of DBD. The results provided fundamental information for further studying the pharmacological mechanisms of DBD, as well as its quality control research.

4.
J Food Biochem ; 46(12): e14461, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36200661

RESUMEN

Tea seed saponins (TSS) are oleanolane-type pentacyclic triterpenoid saponin mixtures with various pharmacological effects. We aimed to explore the effects of a total of 4 weeks intragastric administration of TSS (140 mg/kg·day) combined with aerobic exercise (AE) on lipid metabolism and its associated oxidative stress in HFD-induced obese mice and to investigate the possible molecular mechanisms. TSS + AE intervention significantly reduced body weight and the adiposity index (including subcutaneous, epididymal, perirenal, and abdominal adipose) in obese mice; improved dyslipidemia by lowering serum TC, TG, and LDL-c levels; and increased HDL-c levels. TSS + AE intervention significantly improved hepatic steatosis by inhibiting lipogenetic Acc, Srebp1c, and Scd1 and upregulating lipolysis genes (Pgc1α, Pgc1ß, Pparα, and Cpt1). TSS + AE intervention increased the hepatic protein expression of p-AMPK, SIRT1, and PGC-1α, as well as PPAR-γ and GLUT-4 in skeletal muscle compared with expression in the HFD group. In addition, TSS + AE also modulated oxidative stress in obese mice, which was indicated by the increased serum and liver levels of SOD, GSH, and T-AOC and decreased ROS and MDA levels. These results suggest that TSS + AE intervention can reduce fat accumulation and improve HFD-induced lipid metabolism disorders and oxidative stress. PRACTICAL APPLICATIONS: Obesity is a metabolic disease induced by excess nutritional intake and insufficient energy expenditure. Dietary modifications combined with aerobic exercise are currently an effective method for weight loss. Tea seed saponins (TSS) are a variety of biologically active oleanolane-type pentacyclic triterpenoid saponins that naturally exist in tea seeds. Few articles have focused on the effects and mechanisms of TSS combined with aerobic exercise (AE) in regulating lipid metabolism and improving oxidative damage in vivo. Using an HFD-induced obese mice model to explore the mechanism of TSS + AE in regulating lipid metabolism and its associated oxidative stress damage will help provide reliable data for the application of dietary nutrition combined with AE in anti-obesity.


Asunto(s)
Metabolismo de los Lípidos , Saponinas , Ratones , Animales , Dieta Alta en Grasa/efectos adversos , Saponinas/farmacología , Ratones Obesos , Obesidad/tratamiento farmacológico , Obesidad/etiología , Obesidad/metabolismo , Estrés Oxidativo , Ejercicio Físico , , Triterpenos Pentacíclicos/farmacología
5.
3 Biotech ; 12(9): 188, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35879964

RESUMEN

Floret opening and closure are critical for rice to complete reproductive development. To further understand the molecular mechanism of floret opening and closure in rice, RNA-seq was performed on the floret of Indica and Japonica rice in the state of 1-h before floret opening, at the opening and closure, respectively. Our results show that many differentially expressed genes are produced throughout the floret opening and closure of both Indica and Japonica rice. Differentially expressed genes shared between Indica and Japonica rice at floret opening were involved in seven metabolic pathways, including plant hormone signal transduction, MAPK signaling pathway-plant, starch and sucrose metabolism, alpha-Linolenic acid metabolism, plant-pathogen interaction, diterpenoid biosynthesis, glucuronate interconversions, phenylpropanoid biosynthesis, compared to 1 h before floret opening. In addition, the expression patterns of some genes, OsJAZ13, OsJAZ11 and OsCML1 which the above metabolic pathways, were different between Indica and Japonica rice. Compared to the floret opening, the differentially expressed genes at floret closure were mainly involved in the following three metabolic pathways: Circadian rhythm-plant, sesquiterpenoid and triterpenoid biosynthesis, starch and sucrose metabolism, and thiamine metabolism. This study provides insights into revealing the molecular mechanism of floret opening and closure in rice. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-022-03226-y.

6.
Front Pharmacol ; 12: 722975, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34867326

RESUMEN

Background: Keeping in view the high recurrence rate and risk of ischemic stroke, combinatorial therapy involving traditional Chinese medicine (TCM) with conventional Western medicine (WM) is receiving wider scientific attention. Thus, a systematical analysis was made to explore the efficacy of TCM+WM in the long-term secondary prevention for patients with ischemic stroke. Methods: Qualified inclusion and exclusion criteria were set up beforehand, and two researchers independently read the articles, extracted data, and evaluated the quality of included articles according to Cochrane Reviewer's Handbook 5.1 method. For the sake of comprehensive data acquisition, seven databases from the time of their establishment to May 5, 2021, have been searched completely. Additionally, pairwise meta-analysis was made to compare TCM+WM vs. WM, and network meta-analysis was conducted by frequentist random effects models for the comparison of different kinds of TCM+WM via indirect evidence. The primary outcomes defined were recurrent stroke and NIHSS. Secondary outcomes were fibrinogen (Fib) fasting blood glucose (FBG), triglycerides (TG), and total cholesterol (TC). Safety outcomes were outlined as all-cause mortality and adverse events (AEs). Furthermore, Stata16.0 software was used to accomplish the systematical analysis and cluster analysis. Results: In total, 47 qualified randomized controlled trials (RCTs) including 10,732 patients were taken into consideration. Seven traditional Chinese medicines included in the study are Naoxintong capsule (NXT), Tongxinluo capsule (TXL), Buyang Huanwu decoction (BYHW), Naomaitai capsule (NMT), Dengzhan Shengmai capsule (DZSM), Naoshuantong capsule (NST), and Maixuekang capsule (MXK). With respect to their primary outcomes, all kinds of TCM+WM were significantly more effective than WM (e.g., NXT in recurrent stroke (OR=0.54, P<0.01), TXL in NIHSS (WM=-1.4, P<0.01)). Additionally, the outcomes of cluster analysis indicated that MXK+WM and NST+WM had relatively good preventive effects for recurrent stroke, NIHSS, and all-cause mortality. There was no significant difference in the comparisons of AEs; however, this may arise from the lack of sufficient data. Conclusion: According to our systematical analysis, MXK+WM and NST+WM had relatively good secondary prevention effects for patients with ischemic stroke regarding recurrent stroke, NIHSS, and all-cause mortality. Nevertheless, better, high-quality, large-sample randomized clinical trials (RCTs) are required to verify our conclusions in the future. Systematic Review Registration: [https://inplasy.com/inplasy-2021-5-0036/], identifier [INPLASY202150036].

7.
J Control Release ; 339: 445-472, 2021 11 10.
Artículo en Inglés | MEDLINE | ID: mdl-34637819

RESUMEN

Photoactivated therapeutic strategies (photothermal therapy and photodynamic therapy), due to the adjusted therapeutic area, time and light dosage, have prevailed for the fight against tumors. Currently, the monotherapy with limited treatment effect and undesired side effects is gradually replaced by multimodal and multifunctional nanosystems. Mesoporous silica nanoparticles (MSNs) with unique physicochemical advantages, such as huge specific surface area, controllable pore size and morphology, functionalized modification, satisfying biocompatibility and biodegradability, are considered as promising candidates for multimodal photoactivated cancer therapy. Excitingly, the innovative nanoplatforms based on the mesoporous silica nanoparticles provide more and more effective treatment strategies and display excellent antitumor potential. Given the rapid development of antitumor strategies based on MSNs, this review summarizes the current progress in MSNs-based photoactivated cancer therapy, mainly consists of (1) photothermal therapy-related theranostics; (2) photodynamic therapy-related theranostics; (3) multimodal synergistic therapy, such as chemo-photothermal-photodynamic therapy, phototherapy-immunotherapy and phototherapy-radio therapy. Based on the limited penetration of irradiation light in photoactivated therapy, the challenges faced by deep-seated tumor therapy are fully discussed, and future clinical translation of MSNs-based photoactivated cancer therapy are highlighted.


Asunto(s)
Nanopartículas , Neoplasias , Doxorrubicina/uso terapéutico , Portadores de Fármacos/uso terapéutico , Humanos , Neoplasias/tratamiento farmacológico , Fototerapia , Porosidad , Dióxido de Silicio/uso terapéutico
8.
Artículo en Inglés | MEDLINE | ID: mdl-34221073

RESUMEN

Sympathetic remodeling may cause severe arrhythmia after myocardial infarction (MI). Thus, targeting this process may be an effective strategy for clinical prevention of arrhythmias. LianXia Formula Granule (LXFG) can effectively improve the symptoms of patients with arrhythmia after MI, and modern pharmacological studies have shown that Coptidis Rhizoma and Rhizoma Pinelliae Preparata, the components of LXFG, have antiarrhythmia effects. Here, we investigated whether LXFG can mitigate sympathetic remodeling and suppress arrhythmia and then elucidated its underlying mechanism of action in rats after MI. Sprague-Dawley (SD) rats that had undergone a myocardial infarction model were randomly divided into 6 groups, namely, sham, model, metoprolol, and LXFG groups, with high, medium, and low dosages. We exposed the animals to 30 days of treatment and then evaluated incidence of arrhythmia and arrhythmia scores in vivo using programmed electrical stimulation. Moreover, we determined plasma catecholamines contents via enzyme-linked immunosorbent assay and detected expression of tyrosine hydroxylase (TH) at infarcted border zones via western blot, real-time PCR, and immunohistochemical analyses to assess sympathetic remodeling. Finally, we measured key molecules involved in the NGF/TrKA/PI3K/AKT pathways via western blot and real-time PCR. Compared with the model group, treatment with high dose of LXFG suppressed arrhythmia incidence and arrhythmia scores. In addition, all the LXFG groups significantly decreased protein and mRNA levels of TH, improved the average optical density of TH-positive nerve fibers, and reduced the levels of plasma catecholamines relative to the model group. Meanwhile, expression analysis revealed that key molecules in the NGF/TrKA/PI3K/AKT pathways were downregulated in the LXFG group when compared with model group. Overall, these findings indicate that LXFG suppresses arrhythmia and attenuates sympathetic remodeling in rats after MI. The mechanism is probably regulated by suppression of the NGF/TrKA/PI3K/AKT signaling pathway.

9.
Front Microbiol ; 12: 579006, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34248860

RESUMEN

Intestinal infections are a major cause of morbidity and mortality in humans and agricultural animals, especially newborns and weaned animals. Preventive treatments that help weaned animals maintain homeostasis and balance the hindgut microbial populations are desirable. The present study aimed to explore the impact of bacitracin methylene disalicylate (BMD) on the intestinal health by analyzing the intestinal environment, morphology, expression of peptidoglycan recognition proteins (PGRPs), and flora of weaned rabbits. A total of 300 New Zealand weaned rabbits were randomly divided into the following five treatment groups for a 35-day feed trial: control group (basal diet), bacitracin zinc (BZ) group (50 mg/kg BZ), BMDa group (100 mg/kg BMD), BMDb group (50 mg/kg BMD), and BMDc group (rabbits fed a basal diet supplemented with 25 mg/kg BMD). In each treatment group, 28 rabbits were slaughtered for experimental analysis. The results showed that the supplementation of BMD increased the environmental acidity of the cecum of the weaned rabbits and reduced the ammonia-nitrogen concentration, which was beneficial to the survival of useful bacteria in the intestine. The morphology analysis of the duodenum using hematoxylin and eosin staining revealed that the villus length, villus/crypt ratio, and intestinal wall thickness increased in the BMD group, thereby improving the structure of the duodenum and the absorption capacity of the small intestine. Moreover, real-time polymerase chain reaction test showed that PGRPs (especially PGLYRP-1 and PGLYRP-2) in the intestinal had an antagonistic effect with BMD in the process of inhibiting pathogenic bacteria, resulting in their decreased expression (P < 0.05). Furthermore, through 16S rRNA sequencing in the cecal content, the abundance of the predominant phyla in the BMDa and BZ groups was found to be the closest. The abundance of the genera Lachnospira, Erysipelotrichaceae (p-75-a5), Paraprevotellaceae (YRC22), Mogibacterium, Peptococcaceae (rc4-4), Anaerovibrio, Succinivibrio, and Sphaerochaeta increased in the BMDa and BZ groups (P < 0.05). The relative abundance of Alistipes, Sedimentibacter, and Dorea significantly increased only in the BMDa group (P < 0.05). Conclusively, BMD, as well as microbes, improved the intestinal environment and structure to maintain the intestinal health of weaned rabbits.

10.
Front Med (Lausanne) ; 8: 655231, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34179041

RESUMEN

Background: The ongoing COVID-19 pandemic has brought significant challenges to health system and consumed a lot of health resources. However, evidence on the hospitalization costs and their associated factors in COVID-19 cases is scarce. Objectives: To describe the total and components of hospitalization costs of COVID-19 cases, and investigate the associated factors of costs. Methods: We included 876 confirmed COVID-19 cases admitted to 33 designated hospitals from January 15th to April 27th, 2020 in Guangdong, China, and collected their demographic and clinical information. A multiple linear regression model was performed to estimate the associations of hospitalization costs with potential associated factors. Results: The median of total hospitalization costs of COVID-19 cases was $2,869.4 (IQR: $3,916.8). We found higher total costs in male (% difference: 29.7, 95% CI: 15.5, 45.6) than in female cases, in older cases than in younger ones, in severe cases (% difference: 344.8, 95% CI: 222.5, 513.6) than in mild ones, in cases with clinical aggravation than those without, in cases with clinical symptoms (% difference: 47.7, 95% CI: 26.2, 72.9) than those without, and in cases with comorbidities (% difference: 21.1%, 21.1, 95% CI: 4.4, 40.6) than those without. We also found lower non-pharmacologic therapy costs in cases treated with traditional Chinese medicine (TCM) therapy (% difference: -47.4, 95% CI: -64.5 to -22.0) than cases without. Conclusion: The hospitalization costs of COVID-19 cases in Guangdong were comparable to the national level. Factors associated with higher hospitalization costs included sex, older age, clinical severity and aggravation, clinical symptoms and comorbidities at admission. TCM therapy was found to be associated with lower costs for some non-pharmacologic therapies.

11.
Zhongguo Zhong Yao Za Zhi ; 46(6): 1311-1331, 2021 Mar.
Artículo en Chino | MEDLINE | ID: mdl-33787127

RESUMEN

Kudzu plants in the subfamily sphenoideae of Leguminosae are commonly used herbs in China, Japan, Korea, India and Thailand, with a long history of medicinal use. They are recorded in Chinese Pharmacopoeia, Japanese Pharmacopeia, Korea Pharmacopeia, Ayurveda Pharmacopoeia of India and Flora of Thailand. There are 15-20 species of Pueraria in the world, including 7 species and 2 varieties in China. At present, there are 6 species with medicinal value, such as Pueraria lobata and P. thomsonii. The main chemical components of the genus are isoflavones, flavonoids, terpenes, steroids, coumarins, puerarin glycosides and benzopyrans. A total of 240 compounds have been isolated and identified from this genus, and their pharmacological effects mainly include improvement of the cardiovascular system, antioxidant, hypoglycemic, antipyretic, anti-inflammatory, anti-alcoholic and estrogen-like effects. In this study, chemical constituents and pharmacological activities of Pueraria at home and abroad were systematically summarized, in order to provide references for the material basis, quality control and further development of Pueraria genus.


Asunto(s)
Isoflavonas , Pueraria , China , Isoflavonas/farmacología , Japón , Raíces de Plantas , República de Corea , Tailandia
12.
Pestic Biochem Physiol ; 169: 104650, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32828368

RESUMEN

Sex pheromone-based pest management technology has been widely used to monitor and control insect pests in the agricultural, forestry, and public health sectors. Scopula subpunctaria is a widespread tea pest in China with Type II sex pheromone components. However, limited information is available on the biosynthesis and transportation of Type II sex pheromone components. In this study, we constructed an S. subpunctaria sex pheromone gland (PG) transcriptome and obtained 85,246 transcripts. Cytochrome P450 monooxygenases (CYPs) thought to epoxidize dienes and trienes to epoxides in the PG and odorant-binding proteins (OBPs) and chemosensory genes (CSPs) thought to be responsible for the binding and transportation of sex pheromone components. In present study, a total of 79 CYPs, 29 OBPs and 17 CSPs were identified. We found that SsubCYP341A and SsubCYP341B_ortholog1 belonged to the CYP341 family and were more highly expressed in the PG than in the female body. Of these, SsubCYP341A was the seventh-most PG-enriched CYP in the PG transcriptome. Two CYP4 members, CYP340BD_ortholog2 and CYP4G, were the top two most PG-enriched CYPs. Tissue expression and phylogenetic tree analysis showed that SsubOBP25, 27, and 28 belonged to the moth pheromone-binding protein family; they were distinctly expressed in the antennae and were more abundant in male antennae than in female antennae. SsubCSP16 was distributed into the same clade as CSPs from other moths that showed high binding affinities to sex pheromone components. It indicated that all the above-mentioned genes could be involved in sex pheromone biosynthesis or transportation. Our study provides large-scale PG sequence information that can be used to identify potential targets for the biological control of S. subpunctaria by disrupting its sex pheromone biosynthesis and transportation pathways.


Asunto(s)
Mariposas Nocturnas/genética , Atractivos Sexuales , Animales , Antenas de Artrópodos , China , Sistema Enzimático del Citocromo P-450 , Femenino , Perfilación de la Expresión Génica , Proteínas de Insectos/genética , Masculino , Filogenia , Receptores Odorantes , , Transcriptoma
13.
J Ethnopharmacol ; 263: 113233, 2020 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-32768638

RESUMEN

ETHNOPHARMACOLOGY RELEVANCE: Tacrolimus is a well-known potent but expensive immunosuppressant. We previously clarified the herb-drug interaction between tacrolimus and Wuzhi tablet (WZ), a prescribed drug of ethanol extract of Schisandra sphenanthera, and showed the ideal effect of WZ on maintaining therapeutic level of tacrolimus and reducing the total drug expense. However, WZ possesses a biphasic effect on regulating CYP3A (the major metabolizing enzyme of tacrolimus), which could induce the mRNA and protein expression after long-term treatment while transiently inhibit the activity of CYP3A. In clinic, clinicians are confused about the relationship between the blood concentration of tacrolimus and the dose and the duration of pretreatment of WZ. Therefore, the effects of the pretreatment time and the dose of WZ on the pharmacokinetics of tacrolimus is urgently needed to be clarified to better combine the use of WZ and tacrolimus in clinic. AIM OF THE STUDY AND METHOD: This study aimed to investigate the effects of the pretreatment time and the dose of WZ on the pharmacokinetics of tacrolimus in rats. RESULTS AND CONCLUSIONS: After pretreated rats with WZ for 0, 0.5, 2, 6, 12 or 24 h, the area under the curve (AUC) of tacrolimus was 2.27 ± 0.59, 1.87 ± 1.14, 2.86 ± 0.64, 1.62 ± 0.70, 1.54 ± 1.06 and 1.12 ± 0.69-fold of that of the tacrolimus alone group, respectively. The ratio of AUC of tacrolimus to that of the co-administration group with 0, 62.5, 125, 250, 500 or 750 mg/kg of WZ was 1.00: 1.07: 1.44: 2.60: 2.32: 2.42, respectively. These findings suggested that WZ increased tacrolimus AUC in a pretreatment time- and dose-dependent manner. In line with the in vivo findings, WZ extract inhibited CYP3A activity in a pre-treatment time- and concentration-dependent manner in human liver microsomes. In conclusion, the pharmacokinetics of tacrolimus was significantly affected by the pretreatment time and the dose of WZ. Oral pretreatment with WZ for 0-2 h or co-dosing of 250 mg/kg of WZ most significantly increased the blood concentration of tacrolimus. These findings would be helpful for guiding the reasonable use of WZ and tacrolimus in clinic.


Asunto(s)
Medicamentos Herbarios Chinos/administración & dosificación , Interacciones de Hierba-Droga , Extractos Vegetales/administración & dosificación , Schisandra , Tacrolimus/administración & dosificación , Animales , Relación Dosis-Respuesta a Droga , Medicamentos Herbarios Chinos/metabolismo , Interacciones de Hierba-Droga/fisiología , Inmunosupresores/administración & dosificación , Inmunosupresores/sangre , Masculino , Microsomas Hepáticos/efectos de los fármacos , Microsomas Hepáticos/metabolismo , Extractos Vegetales/sangre , Ratas , Ratas Sprague-Dawley , Comprimidos , Tacrolimus/sangre , Factores de Tiempo
14.
Biomed Pharmacother ; 129: 110436, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32768938

RESUMEN

The present study investigates the differences in inflammatory agents alterations, immune function, and leukocyte differential count evaluation in severe pneumonia of SARS-COV-2 patients with Yidu-toxicity blocking lung syndrome after the recommended Chinese medicine prescription of Yidu-toxicity blocking lung decoction. A total of 40 patients with yidu-toxicity blocking lung syndrome, diagnosed as severe pneumonia of SARS-COV-2 following the latest Chinese national recommendations for the diagnosis and treatment of pneumonia caused by SARS-COV-2 (the 5th edition), were recruited. They were randomly divided into the pure western medicine therapy group (PWM) and integrated into Chinese and Western medicine therapy group (ICW). The general strategies were given to both groups according to the national recommendations, and the ICW group was given Yidu-toxicity blocking lung decoction extraorally. A radioimmunoassay method was adopted to detect the content of IL-6, IL-8,IL-2R,TNF-α, procalcitonin (PCT) and high-sensitivity C-reactive protein (hs-CRP) in sera. Flow cytometry was used to determine the peripheral blood lymphocyte subsets (the levels of CD3+, CD4+, CD8+, and the ratios of CD4+/CD8+). The white blood cell counts (WBC#), neutrophils count(N#), and lymphocyte counts (L#) were measured using a fully automatic blood rheological instrument. The t-test or Rank Sum Test and Spearman analysis were conducted to evaluate the differences. The results showed that IL-6 (P = 0.013) and TNF-α (P = 0.035) levels in the PWM group were significantly higher than those in the ICW group after treatment. Infection related indicators such as WBC#, N#, L#, hs-CRP showed no differences. The analysis showed that there was no statistical difference in the values of CD4 and CD8 between the two groups. By the end of Day 29, all patients were discharged and the final cure rate for both group were 100 %. Taken together, we conclude that Yidu-toxicity blocking lung decoction could relieve inflammation of SARS-COV-2 patients with yidu-toxicity blocking lung syndrome by eliminating inflammatory agents. CM can serve as a complementary medication to western medicine, which should be highlighted in clinical settings.


Asunto(s)
Infecciones por Coronavirus/tratamiento farmacológico , Medicamentos Herbarios Chinos/farmacología , Inflamación/tratamiento farmacológico , Neumonía Viral/tratamiento farmacológico , Betacoronavirus/efectos de los fármacos , Betacoronavirus/aislamiento & purificación , COVID-19 , Infecciones por Coronavirus/virología , Medicamentos Herbarios Chinos/administración & dosificación , Femenino , Humanos , Inflamación/virología , Interleucina-6/metabolismo , Recuento de Leucocitos , Recuento de Linfocitos , Subgrupos Linfocitarios , Masculino , Persona de Mediana Edad , Pandemias , Neumonía Viral/virología , SARS-CoV-2 , Índice de Severidad de la Enfermedad , Factor de Necrosis Tumoral alfa/metabolismo , Tratamiento Farmacológico de COVID-19
15.
Artículo en Inglés | MEDLINE | ID: mdl-32454874

RESUMEN

Gastric precancerous lesions (GPLs) are an essential precursor in the occurrence and development of gastric cancer, known to be one of the most common and lethal cancers worldwide. Traditional Chinese medicine (TCM) has a positive prospect for the prevention and therapy of GPL owing to several advantages including a definite curative effect, fewer side effects compared to other treatments, multiple components, and holistic regulation. Despite these characteristic advantages, the mechanisms of TCM in treating GPL have not been fully elucidated. In this review, we summarize the current knowledge with respect to herbal formulations and the therapeutic mechanisms of TCM active ingredients for GPL. This paper elaborates on the mechanisms of TCM underlying the prevention and treatment of GPL, specifically those that are linked to anti-H. pylori, anti-inflammation, antiproliferation, proapoptotic, antioxidation, antiglycolytic, and antiangiogenesis effects.

16.
NMR Biomed ; 33(6): e4293, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32175654

RESUMEN

Enteric contrast agents are important in gastrointestinal MRI. However, no currently available agent is well established as the standard of care. In this study, in vitro relaxivities of manganese threonine chelate (Mn-Thr), a common nutritional food supplement, were measured at 1.5 T and 3 T with further investigation of its efficacy and safety in vivo as an enteric contrast agent. According to the calculated relaxivities, T1 W and T2 W TSE sequences of Mn-Thr solutions at different concentrations were acquired, and the optimal concentration for dark lumen imaging on both T1 W and T2 W images was determined in vitro. To validate the optimal concentration in vivo, eight Sprague-Dawley rats were randomly divided into two groups. Each group received rectal injection of either 2.00 g/L (about 3.80 mM) Mn-Thr or saline as an enteric contrast agent and underwent MRI. After a time interval of one week, the same procedures were repeated with the alternative contrast agent. Animals were sacrificed after the second MRI. Tissue manganese quantification and histopathological examination were obtained. Qualitative MR image quality assessments were performed and compared between Mn-Thr and saline. Measured T1 and T2 relaxivities of Mn-Thr were significantly higher than those of MnCl2 in vitro (p < 0.05). At the concentration of 2.00 g/L (about 3.80 mM), Mn-Thr produced a dark lumen on T1 W and T2 W images both in vitro and in vivo. Compared with saline, Mn-Thr showed significantly more homogenous luminal signal and increased bowel wall conspicuity in image quality assessments. Tissue manganese concentrations were not significantly different between two groups. Histopathological examinations were normal in both groups. Our data suggest that Mn-Thr possesses favorable paramagnetic properties and can create a homogenous dark lumen on T1 W and T2 W images without obvious side effects in healthy rats. As a commercially available nutritional food supplement, Mn-Thr appears to be a promising enteric contrast agent for MRI.


Asunto(s)
Quelantes/química , Imagen por Resonancia Magnética , Manganeso/química , Treonina/química , Animales , Especificidad de Órganos , Fantasmas de Imagen , Proyectos Piloto , Ratas Sprague-Dawley
17.
Artículo en Inglés | MEDLINE | ID: mdl-33424994

RESUMEN

OBJECTIVE: Intermittent theta burst stimulation (iTBS) is a widely used noninvasive brain stimulation for the facilitation of corticospinal excitability (CSE). Previous studies have shown that acupuncture applied to acupoints associated with motor function in healthy people can reduce the amplitude of the motor-evoked potentials (MEPs), which reflects the inhibition of CSE. In our work, we wanted to test whether the combination of iTBS and electroacupuncture (EA) would have different effects on CSE in humans. METHODS: A single-blind sham-controlled crossover design study was conducted on 20 healthy subjects. Subjects received 20 minutes' sham or real EA stimulation immediately after sham or real iTBS. MEPs, short-interval intracortical inhibition (SICI), intracortical facilitation (ICF), cortical silent period (CSP), and central motor conduction time (CMCT) were recorded before each trial, and immediately, 20 minutes, and 40 minutes after the end of stimulation. RESULTS: In the sham iTBS group, EA produced a reduction in MEPs amplitude, lasting approximately 40 minutes, while in the real iTBS group, EA significantly increased MEPs amplitude beyond 40 minutes after the end of stimulation. In sham EA group, the recorded MEPs amplitude showed no significant trend over time compared to baseline. Among all experiments, there were no significant changes in SICI, ICF, CSP, CMCT, etc. CONCLUSION: These data indicate that immediate application of EA after iTBS significantly increased corticospinal excitability. This trial was registered in the Chinese Clinical Trial Registry (registration no. ChiCTR1900025348).

18.
Environ Sci Pollut Res Int ; 27(4): 4478-4488, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31832950

RESUMEN

In the process of electrokinetic (EK) remediation of uranium-contaminated soil, the existence form of uranium in soil pore fluid will affect on its migration behavior. In this paper, a novel type of electrolyte (citric acid + ferric chloride, CA+ FeCl3) has been investigated for the EK remediation of uranium-contaminated red soil. The effects of different electrolyte and the concentrations of FeCl3 on migration behavior of U(VI) and environmental risks were investigated after EK remediation. The result showed that the optimum concentration was 0.1 mol/L CA mixed with 0.03 mol/L FeCl3 in this study. At this time, the removal efficiency of uranium was about 61.55 ± 0.41%, and the cumulative energy consumption was 0.2559 kWh. Compared with deionized water and single CA, combined CA with FeCl3 has the advantages of high removal efficiency, low leaching toxicity, and less damage to the soil after the electrokinetic remediation treatment.


Asunto(s)
Cloruros/química , Ácido Cítrico/química , Restauración y Remediación Ambiental , Compuestos Férricos/química , Contaminantes del Suelo , Uranio , Electrólitos , Suelo , Uranio/química
19.
Artículo en Inglés | MEDLINE | ID: mdl-30854000

RESUMEN

The Wei Pi Xiao (WPX) decoction, based on the theory of traditional Chinese medicine, has been widely used for the treatment of gastric precancerous lesions (GPL). Although WPX is known to be effective for the treatment of GPL, its active ingredients, cellular targets, and the precise molecular mechanism of action are not known. This study aimed to identify the multiple mechanisms of action of the WPX decoction in the treatment of GPL. The active compounds, drug targets, and the key pathways involved in the therapeutic effect of WPX in the treatment of GPL were analyzed by an integrative analysis pipeline. The information pertaining to the compounds present in WPX and their disease targets was obtained from TCMSP and GeneCards, respectively. The mechanisms underlying the therapeutic effect of WPX were investigated with gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. A total of 82 bioactive compounds and 146 related targets were identified in this study. Following target analyses, the targets were further mapped to 26 key biological processes and 21 related pathways to construct a target-pathway network and an integrated GPL pathway. The study demonstrated that the WPX formula primarily treats the dysfunctions of GPL arising from cell proliferation, apoptosis, and mucosal inflammation, which offered a novel insight into the pathogenesis of GPL and revealed the molecular mechanism underlying the therapeutic effects of the WPX formula in GPL. This study offers a novel approach for the systematic investigation of the mechanisms of action of herbal medicines, which will provide an impetus to the GPL drug development pipeline.

20.
Drug Metab Dispos ; 45(11): 1114-1119, 2017 11.
Artículo en Inglés | MEDLINE | ID: mdl-28864749

RESUMEN

Tacrolimus is a potent but expensive first-line immunosuppressant, thus solutions to reduce tacrolimus consumption while maintain therapeutic level are in urgent need. A two-phase prospective study was conducted to assess the efficacy of an ethanolic extraction preparation of Schisandra sphenanthera (Wuzhi tablet) as a tacrolimus-sparing agent in renal transplant recipients who were high-dose tacrolimus consumers (CYP3A5*1 allele carriers, CYP3A5 expressers). A total of 12 patients were included in the Part I study. After co-administration of Wuzhi tablet, the average individual increment (%) in dose-adjusted C0, Cmax and AUC0-12 hour of tacrolimus were 198.8% (95% CI 149.2, 248.3), 111.0% (95% CI 63.4, 158.6) and 126.1% (95% CI 89.4, 162.8), respectively (P < 0.01), while the average individual reduction (%) in tacrolimus daily dose was 40.9% (95% CI 25.2, 56.6) (P < 0.01). Subsequently, 32 patients were enrolled in a prospective, randomized, controlled study and randomly assigned to receive tacrolimus by CYP3A5 genotype plus Wuzhi tablet co-administration guided dosing (study group) or standard dosing (control group). Besides less tacrolimus dose requirement (P < 0.01), a more accurate tacrolimus initial dose characterized by lower incidence of out-of-range C0 after initial dose (P < 0.01) and fewer dose changes (P < 0.01) was found in the study group. Moreover, no significant differences in acute rejection rate and serum creatinine levels were observed between two groups. Our results show that CYP3A5 genotype plus Wuzhi tablet co-administration guided tacrolimus dosing is a promising therapy for CYP3A5 expressers in the early post-transplant stage, while further study with a larger sample size is required to prove these findings.


Asunto(s)
Citocromo P-450 CYP3A/genética , Medicamentos Herbarios Chinos/uso terapéutico , Rechazo de Injerto/prevención & control , Inmunosupresores/uso terapéutico , Trasplante de Riñón/efectos adversos , Schisandra/química , Adulto , Área Bajo la Curva , Citocromo P-450 CYP3A/metabolismo , Relación Dosis-Respuesta a Droga , Medicamentos Herbarios Chinos/economía , Medicamentos Herbarios Chinos/farmacología , Femenino , Humanos , Inmunosupresores/economía , Inmunosupresores/farmacología , Masculino , Persona de Mediana Edad , Variantes Farmacogenómicas , Estudios Prospectivos , Comprimidos , Tacrolimus/economía , Tacrolimus/farmacología , Tacrolimus/uso terapéutico , Resultado del Tratamiento , Adulto Joven
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