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1.
Sci Rep ; 14(1): 12973, 2024 06 05.
Artículo en Inglés | MEDLINE | ID: mdl-38839818

RESUMEN

This study addresses the challenge of accurately diagnosing sepsis subtypes in elderly patients, particularly distinguishing between Escherichia coli (E. coli) and non-E. coli infections. Utilizing machine learning, we conducted a retrospective analysis of 119 elderly sepsis patients, employing a random forest model to evaluate clinical biomarkers and infection sites. The model demonstrated high diagnostic accuracy, with an overall accuracy of 87.5%, and impressive precision and recall rates of 93.3% and 87.5%, respectively. It identified infection sites, platelet distribution width, reduced platelet count, and procalcitonin levels as key predictors. The model achieved an F1 Score of 90.3% and an area under the receiver operating characteristic curve of 88.0%, effectively differentiating between sepsis subtypes. Similarly, logistic regression and least absolute shrinkage and selection operator analysis underscored the significance of infectious sites. This methodology shows promise for enhancing elderly sepsis diagnosis and contributing to the advancement of precision medicine in the field of infectious diseases.


Asunto(s)
Biomarcadores , Infecciones por Escherichia coli , Escherichia coli , Aprendizaje Automático , Sepsis , Humanos , Anciano , Sepsis/diagnóstico , Sepsis/microbiología , Sepsis/sangre , Biomarcadores/sangre , Masculino , Femenino , Infecciones por Escherichia coli/diagnóstico , Infecciones por Escherichia coli/microbiología , Infecciones por Escherichia coli/sangre , Anciano de 80 o más Años , Escherichia coli/aislamiento & purificación , Estudios Retrospectivos , Curva ROC , Polipéptido alfa Relacionado con Calcitonina/sangre , Bosques Aleatorios
2.
Fitoterapia ; 176: 106009, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38759735

RESUMEN

Euphorbia himalayensis Boiss. is an alpine member of the Euphorbiaceae family. Its dried roots have been used to treat digestive problems and chest congestion in traditional Tibetan and Mongolian medicine. Despite thousands of years of use in medicine, the bioactive compounds of the root remain unknown. Herein, we isolated a novel aqueous-soluble polysaccharide (EHP2) from the E. himalayensis root and determined its structural characteristics via high-performance gel permeation chromatography, Fourier-transform infrared spectroscopy, gas chromatography-mass spectrometry, and nuclear magnetic resonance spectrometry. The homogeneous molecular weight of EHP2 was 23.6 kDa with narrow polydisperity (Mw/Mn = 1.4), and EHP2 mainly comprised of glucose (86.4%), galactose (11.9%) and mannose (1.7%). The major backbone of EHP2 was →4)-α-D-GalAp-(1 â†’ 4)-α-D-Glcp-(1 â†’ and the branch chain was α-D-Glcp-(1→. The antioxidant activity of the EHP2 was evaluated by 1,1-diphenyl-2-picrylhydrazyl (DPPH) and superoxide anion radical scavenging assays, and antioxidant enzyme activity (SOD, GSH and MDA) was determined in human umbilical vein endothelial cells (HUVECs). The EHP2 demonstrated lower potential scavenging effects on DPPH and superoxide free radical scavenger than ascorbic acid, and in HUVECs, it led to increased SOD and GSH activities and decreased MDA levels. This study is the first to describe an E. himalayensis polysaccharide compound with potential antioxidant activity.


Asunto(s)
Antioxidantes , Euphorbia , Células Endoteliales de la Vena Umbilical Humana , Raíces de Plantas , Polisacáridos , Euphorbia/química , Antioxidantes/farmacología , Antioxidantes/aislamiento & purificación , Polisacáridos/farmacología , Polisacáridos/aislamiento & purificación , Polisacáridos/química , Raíces de Plantas/química , Humanos , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Estructura Molecular , Fitoquímicos/farmacología , Fitoquímicos/aislamiento & purificación
3.
Ying Yong Sheng Tai Xue Bao ; 35(1): 49-54, 2024 Jan.
Artículo en Chino | MEDLINE | ID: mdl-38511439

RESUMEN

To reveal the key factors influencing vegetation productivity in sandy lands, we conducted a comprehensive analysis of vegetation productivity on regional scale, pixel scale, and plot scale of the sandy lands in northwes-tern Liaoning Province, based on soil physicochemical data, topographical data, climate data, and the intrinsic characteristics of vegetation. On the regional scale, we established a random forest model to explore the impact of topographical factors, climate factors, and vegetation characteristics on vegetation productivity. On the pixel scale, we performed a correlation analysis between vegetation cover and climate factors. On the plot scale, we combined the physicochemical properties of 234 soil samples with topographical factors and vegetation characteristics, and utilized the random forest model to calculate the importance values of each factor. The results showed that soil nutrients could explain 24.8% of the spatial variation in net primary productivity when other factors were excluded. When introducing topographical factors into the model, the model could explain 40% variation of net primary productivity. When further incorporating fractional vegetation coverage and leaf area index into the model, the model could explain 72.8% variation of net primary productivity. Our findings suggested that fractional vegetation coverage and leaf area index were the most influential factors affecting vegetation productivity in this area. Topographical factors ranked second, followed by climate factors, which had a relatively small impact.


Asunto(s)
Ecosistema , Arena , Clima , Suelo/química , China , Cambio Climático
4.
Pharmacol Res Perspect ; 12(2): e1187, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38546116

RESUMEN

The progression of chronic kidney diseases (CKD) is complex, influenced by a myriad of factors including gut microbiota. While emerging evidence suggests that gut microbiota can have beneficial effects in managing CKD, it is also recognized that dysbiosis may contribute to the progression of CKD and associated uremic complications. Our previous research has demonstrated the efficacy of lanthanum hydroxide in delaying kidney failure and preserving renal function. However, the role of lanthanum hydroxide in modulating gut microbiota in this context remains unclear. In our study, we induced CKD in rats using adenine, leading to gut microbial dysbiosis, kidney pathology, and disturbances in amino acid metabolism. In this adenine-induced CKD model with hyperphosphatemia, treatment with lanthanum hydroxide improved renal function. This improvement was associated with the restoration of gut microbial balance and an increase in urine ammonium metabolism. These results suggest that the therapeutic potential of lanthanum hydroxide in CKD may be partly due to its ability to reshape gut microbiota composition. This study underscores the significance of lanthanum hydroxide in kidney protection, attributing its benefits to the modulation of gut microbiota in a rat model of CKD.


Asunto(s)
Microbioma Gastrointestinal , Lantano , Insuficiencia Renal Crónica , Ratas , Animales , Disbiosis , Riñón/metabolismo , Insuficiencia Renal Crónica/metabolismo , Adenina
5.
World J Gastrointest Oncol ; 15(8): 1400-1411, 2023 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-37663938

RESUMEN

BACKGROUND: Resistance to sorafenib has become a challenge in clinical treatment of hepatocellular carcinoma (HCC). Physcion is a common bioactive anthraquinone that has potential as an anticancer agent. AIM: To study the effect of physcion on sensitizing HCC cells to sorafenib. METHODS: Sorafenib-resistant HCC cells were established and treated with sorafenib and/or physcion. The cell viability, proliferation and apoptosis were measured by cell counting kit-8, colony formation, flow cytometry, and in vivo xenograft model. Glucose uptake, lactate acid production, extracellular acidification rate (ECAR), and oxygen consumption rate (OCR) were measured to analyze glycolysis. Expression of glycolysis-related regulators was assessed by western blotting. RESULTS: The addition of physcion significantly enhanced the antitumor effects of sorafenib on sorafenib-resistant HCC cells, manifested by enhanced apoptosis and suppressed cell growth. The glucose uptake, lactate acid production, and ECAR were elevated, and OCR was suppressed by physcion treatment. The level of PIM1 was elevated and miR-370 was suppressed in sorafenib-resistant HCC cells compared with the parental cells, which was suppressed by physcion treatment. Inhibition of miR-370 notably reversed the effects of physcion on sorafenib-resistant HCC cells. CONCLUSION: Our data indicated that physcion enhanced the sensitivity of HCC cells to sorafenib by enhancing miR-370 to suppress PIM1-promoted glycolysis.

6.
Asian J Androl ; 25(1): 119-125, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-35899921

RESUMEN

The hemodynamic characteristics of venous reflux are associated with infertility in patients with varicocele; however, an effective method for quantifying the structural distribution of the reflux is lacking. This study aimed to predict surgical outcomes using a new software for venous reflux quantification. This was a retrospective cohort study of a consecutive series of 105 patients (age range: 22-44 years) between July 2017 and September 2019. Venous reflux of the varicocele was obtained using the Valsalva maneuver during scrotal Doppler ultrasonography before microsurgical varicocelectomy. Using this software, the colored reflux signals were segmented, and the gray scale of the color pixels representing the reflux velocity was comprehensively quantified into the mean reflux velocity of the green layer (MRVG) and the reflux velocity standard deviation of the green layer (RVSDG). Spontaneous pregnancy and changes from baseline in the semen parameters were assessed during a 12-month follow-up period. Data were analyzed using logistic regression analysis. An association of the high MRVG group with impaired progressive motility (odds ratio [OR] = 2.868, 95% confidence interval [CI]: 1.133-7.265) and impaired sperm concentration (OR = 2.943, 95% CI: 1.196-7.239) was found during multivariate analysis. High MRVG (OR = 2.680, 95% CI: 1.086-6.614) and high RVSDG (OR = 2.508, 95% CI: 1.030-6.111) were found to be independent predictors of failure to achieve pregnancy following microsurgical repair. In summary, intense venous reflux is an independent predictor of impaired progressive motility, sperm concentration, and pregnancy outcomes after microsurgical varicocelectomy.


Asunto(s)
Infertilidad Masculina , Varicocele , Embarazo , Femenino , Humanos , Masculino , Adulto Joven , Adulto , Varicocele/complicaciones , Varicocele/diagnóstico por imagen , Varicocele/cirugía , Estudios Retrospectivos , Semen , Venas/cirugía , Recuento de Espermatozoides , Infertilidad Masculina/diagnóstico por imagen , Infertilidad Masculina/etiología , Infertilidad Masculina/cirugía , Microcirugia/métodos , Motilidad Espermática
7.
Proc Jpn Acad Ser B Phys Biol Sci ; 98(7): 361-377, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35908957

RESUMEN

Previous studies showed that lanthanum hydroxide (LH) has a therapeutic effect on chronic kidney disease (CKD) and vascular calcification, which suggests that it might have clinical value. However, the target and mechanism of action of LH are unclear. Metabolomics of clinical samples can be used to predict the mechanism of drug action. In this study, metabolomic profiles in patients with end-stage renal disease (ESRD) were used to screen related signaling pathways, and we verified the influence of LH on the ROS-PI3K-AKT-mTOR-HIF-1α signaling pathway by western blotting and quantitative real-time RT-qPCR in vivo and in vitro. We found that ROS and SLC16A10 genes were activated in patients with ESRD. The SLC16A10 gene is associated with six significant metabolites (L-cysteine, L-cystine, L-isoleucine, L-arginine, L-aspartic acid, and L-phenylalanine) and the PI3K-AKT signaling pathway. The results showed that LH inhibits the ESRD process and its cardiovascular complications by inhibiting the ROS-PI3K-AKT-mTOR-HIF-1α signaling pathway. Collectively, LH may be a candidate phosphorus binder for the treatment of vascular calcification in ESRD.


Asunto(s)
Sistemas de Transporte de Aminoácidos Neutros , Fallo Renal Crónico , Insuficiencia Renal Crónica , Calcificación Vascular , Humanos , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/tratamiento farmacológico , Lantano , Metabolómica , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/tratamiento farmacológico , Serina-Treonina Quinasas TOR/genética , Serina-Treonina Quinasas TOR/metabolismo , Calcificación Vascular/tratamiento farmacológico , Calcificación Vascular/genética
8.
ChemistryOpen ; 11(5): e202200042, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35585035

RESUMEN

The present study reports an innovative finding that alumina containing water or primary alcohol catalyzes the hydrolysis or alcoholysis, respectively, of the product formed through AlCl3 -mediated Friedel-Crafts alkylation of methyl-substituted benzenes and CHCl3 . The former and later reactions mainly provided hydroxy- and alkoxy-substituted diarylmethanes, respectively, while the reference reactions without alumina provided bisarylchloromethane. This method enables the selective syntheses of diphenylmethanol derivatives with very simple procedures, without expensive reagents and apparatuses. Furthermore, the alumina used in the reaction could be recycled by washing with water and subsequent drying. From the viewpoint of material recycling, this function is very important for the development of sustainable chemical reactions.


Asunto(s)
Óxido de Aluminio , Indoles , Alquilación , Benceno , Catálisis , Hidrólisis , Estructura Molecular , Estereoisomerismo , Agua
9.
Cell Biol Int ; 46(8): 1275-1287, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35544947

RESUMEN

The main reason for the high incidence of cardiovascular disease in chronic kidney disease (CKD) patients with vascular calcification (VC) is also the main cause of death in CKD patients. Lanthanum hydroxide (LH) has an inhibitory effect on VC in chronic renal failure; however, the mechanism of its inhibition is poorly defined. Here, we used network pharmacology analysis and found that hypoxia-inducible factor (HIF) is related to VC. In a CKD rat model induced by adenine combined with high phosphorus (1.2%), LH improved the survival rate and inhibited the occurrence and development of VC. In an in vitro study, we found that lanthanum chloride inhibited the occurrence of VC induced by high phosphorus and reduced the production of reactive oxygen species. This study thus revealed that LH can inhibit the occurrence and development of VC by inhibiting the activation of HIF-1.


Asunto(s)
Enfermedades Cardiovasculares , Insuficiencia Renal Crónica , Calcificación Vascular , Animales , Lantano , Fósforo/efectos adversos , Ratas , Calcificación Vascular/inducido químicamente , Calcificación Vascular/tratamiento farmacológico , Calcificación Vascular/metabolismo
10.
Ying Yong Sheng Tai Xue Bao ; 33(12): 3294-3302, 2022 Dec.
Artículo en Chino | MEDLINE | ID: mdl-36601834

RESUMEN

Functional traits of seeds reflect plant reproductive strategies adapting to environmental changes, which is an evolutionary behavior in natural selection and genetics. Study on seed functional traits is of great significance to deeply understand the long-term adaptive evolution of plants and seeds. We measured seed functional traits of a main indigenous species Phragmites australis, including seed size, seed weight, seed set, and seed production, in nine coastal marshes of the six provinces/cities along the coastal zone of China (21°29'-40°57' N), and analyzed latitudinal variations of functional traits. The results showed that seed functional traits of P. australis in Chinese coastal marshes varied significantly with latitude and that there were significant correlations among different traits. Seed size (including seed length, seed width, seed shape index, aspect ratio, and seed surface area), and 100-seed weight showed significant quadratic function relation with latitude, which firstly decreased and then increased with the increases of latitude, while seed setting rate firstly increased and then reduced. There was a trade-off between the number and size of P. australis seeds. Seed production per unit area significantly increased with latitude. Results of stepwise regression analysis showed that climatic factors were the main driver resulting in the difference of seed functional traits of P. australis between latitudes, followed by pH and salinity of soil porewater.


Asunto(s)
Humedales , Humanos , Fenotipo , Poaceae , Semillas , China
12.
Aging (Albany NY) ; 13(11): 15320-15335, 2021 06 03.
Artículo en Inglés | MEDLINE | ID: mdl-34081627

RESUMEN

Recent evidence suggests alterations in the gut microbiota-brain axis may drive cognitive impairment with aging. In the present study, we observed that prolonged administration of D-galactose to mice induced cognitive decline, gut microbial dysbiosis, peripheral inflammation, and oxidative stress. In this model of age-related cognitive decline, Cistanche deserticola polysaccharides (CDPS) improved cognitive function in D-galactose-treated mice by restoring gut microbial homeostasis, thereby reducing oxidative stress and peripheral inflammation. The beneficial effects of CDPS in these aging model mice were abolished through ablation of gut microbiota with antibiotics or immunosuppression with cyclophosphamide. Serum metabolomic profiling showed that levels of creatinine, valine, L-methionine, o-Toluidine, N-ethylaniline, uric acid and proline were all altered in the aging model mice, but were restored by CDPS. These findings demonstrated that CDPS improves cognitive function in a D-galactose-induced aging model in mice by restoring homeostasis of the gut microbiota-brain axis, which alleviated an amino acid imbalance, peripheral inflammation, and oxidative stress. CDPS thus shows therapeutic potential for patients with memory and learning disorders, especially those related to gut microbial dysbiosis.


Asunto(s)
Envejecimiento/patología , Encéfalo/patología , Cistanche/química , Disfunción Cognitiva/tratamiento farmacológico , Disfunción Cognitiva/microbiología , Microbioma Gastrointestinal/efectos de los fármacos , Modelos Biológicos , Polisacáridos/uso terapéutico , Aminoácidos/metabolismo , Animales , Disfunción Cognitiva/complicaciones , Disfunción Cognitiva/inmunología , Citocinas/metabolismo , Disbiosis/complicaciones , Disbiosis/microbiología , Galactosa , Homeostasis , Inflamación/patología , Mediadores de Inflamación/metabolismo , Masculino , Trastornos de la Memoria/complicaciones , Ratones , Degeneración Nerviosa/complicaciones , Degeneración Nerviosa/patología , Estrés Oxidativo/efectos de los fármacos , Polisacáridos/farmacología , Purinas/metabolismo
13.
Front Cell Dev Biol ; 9: 639127, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33928079

RESUMEN

OBJECTIVE: The present work aimed to explore the efficacy of lanthanum hydroxide in managing the vascular calcification induced by hyperphosphate in chronic renal failure (CRF) as well as the underlying mechanism. METHODS: Rats were randomly allocated to five groups: normal diet control, CKD hyperphosphatemia model, CKD model treated with lanthanum hydroxide, CKD model receiving lanthanum carbonate treatment, together with CKD model receiving calcium carbonate treatment. The serum biochemical and kidney histopathological parameters were analyzed. The aortic vessels were subjected to Von Kossa staining, CT scan and proteomic analysis. In vitro, the calcium content and ALP activity were measured, and RT-PCR (SM22α, Runx2, BMP-2, and TRAF6) and Western blot (SM22α, Runx2, BMP-2, TRAF6, and NF-κB) were performed. RESULTS: In the lanthanum hydroxide group, serum biochemical and kidney histopathological parameters were significantly improved compared with the model group, indicating the efficacy of lanthanum hydroxide in postponing CRF progression and in protecting renal function. In addition, applying lanthanum hydroxide postponed hyperphosphatemia-mediated vascular calcification in CKD. Furthermore, lanthanum hydroxide was found to mitigate vascular calcification via the NF-κB signal transduction pathway. For the cultured VSMCs, lanthanum chloride (LaCl3) alleviated phosphate-mediated calcification and suppressed the activation of NF-κB as well as osteo-/chondrogenic signal transduction. Lanthanum hydroxide evidently downregulated NF-κB, BMP-2, Runx2, and TRAF6 expression. CONCLUSION: Lanthanum hydroxide protects against renal failure and reduces the phosphorus level in serum to postpone vascular calcification progression.

14.
Sci Rep ; 11(1): 664, 2021 01 12.
Artículo en Inglés | MEDLINE | ID: mdl-33437022

RESUMEN

Sanwei-Tanxiang powder (SWTX), a traditional Mongolian and Tibetan medicine containing a cocktail of active molecules, relieves angina pectoris and improves recovery in patients with coronary heart disease (CHD). The pharmacological effect of SWTX on CHD was analyzed at a systemic point of view in our previous studies. The bioinformatics prediction showed that the PI3K/Akt/FoxO3a pathway was one of important pathways of SWTX on treatment of coronary heart disease. Based on it, the aim of this study was to evaluate the benefits of SWTX in acute myocardial ischemic-reperfused (MIR) rat in vivo and H9c2 cardiomyoblast cells under oxidative stress induced by H2O2 in vitro, and further investigate the involvement of PI3K/Akt/FoxO3a pathway in these processes. Ex vivo, under physiological conditions, SWTX did not show any modification in the heart rate and contraction amplitude. However, against a MIR injury, SWTX pretreatment provided significant protection, including reduced ST-segment elevation, pathological changes and myocardial infarct size in vivo, meanwhile, some monomers of SWTX showed antioxidant capacity and inhibited cardiomyocytic apoptosis in vitro. The effect was correlated with the activation of the PI3K/Akt/FoxO3a signaling pathway downstream and the regulation of downstream pro-apoptotic Bim of FoxO3a experimental verified by qRT-PCR, Western blot and immunofluorescent assay. In vitro, blocking Akt and p-FoxO3a activation with the PI3K inhibitor LY294002 effectively suppressed the protective effects of several active monomers (including quercetin, macelignan,methyleugenol and Santol) of SWTX against H2O2-induced injury. Collectively, these results suggest that SWTX decreases I/R injury, and the PI3K/Akt/FoxO3a pathway takes part in protection during this process, gallogen (G3) and quercetin (G8) of GZ, methyleugenol (R2) and macelignan (R7) of RDK, santol (T1) of TX are responsible at least in part for SWTX's cardioprotection effect.


Asunto(s)
Cardiotónicos/farmacología , Medicamentos Herbarios Chinos/farmacología , Daño por Reperfusión Miocárdica/prevención & control , Polvos/farmacología , Animales , Apoptosis , Combinación de Medicamentos , Masculino , Daño por Reperfusión Miocárdica/etiología , Daño por Reperfusión Miocárdica/metabolismo , Ratas , Ratas Sprague-Dawley , Transducción de Señal
15.
Artículo en Inglés | MEDLINE | ID: mdl-35003312

RESUMEN

Modified Tabusen-2 decoction (MTBD) is traditional Chinese Mongolia medicine, mainly used to treat osteoporosis. However, the precise material basis of this prescription is not yet fully elucidated. Herein, we establish an HPLC-Q-Exactive MS/MS spectrometer method with four-step characteristic ion filtering (FSCIF) strategy to quickly and effectively identify the structural features of MTBD and determine the representative compounds content. The FSCIF strategy included database establishment, characteristic ions summarization, neutral loss fragments screening, and secondary mass spectrum fragment matching four steps. By using this strategy, a total of 143 compounds were unambiguously or tentatively annotated, including 5 compounds which were first reported in MTBD. Nineteen representative components were simultaneously quantified with the HPLC-Q-Exactive MS/MS spectrometer, and it is suitable for eight batches of MTBD. Methodology analysis showed that the assay method had good repeatability, accuracy, and stability. The method established above was successfully applied to assess the quality of MTBD extracts. Collectively, our findings enhance our molecular understanding of the MTBD formulation and will allow us to control its quality in a better way. At the same time, this study can promote the development and utilization of ethnic medicine.

16.
Front Pharmacol ; 11: 581991, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33178024

RESUMEN

Post-menopausal osteoporosis (PMOP) is associated with estrogen deficiency and worldwide, is becoming increasingly more prevalent in aging women. Various anti-PMOP drugs have been developed to reduce the burden of PMOP; generally, these drugs are efficacious, but with some adverse side effects. Tubson-2 decoction (TBD), a popular traditional Mongolian medicine, has been used to treat PMOP for centuries. However, the precise mechanisms underlying the action of TBD on PMOP have yet to be fully elucidated. Herein, we combined network pharmacology with untargeted metabolomics to identify the key targets and metabolic pathways associated with the interventional effects of TBD on ovariectomized (OVX) rats. Furthermore, we investigated the bone histomorphometry of eight different groups of rats to evaluate the therapeutic effect of TBD. First, we established a TBD-target/PMOP network via network pharmacology; this network identified three key protein targets-vitamin D receptor (VDR), cytochrome P450 19A1 (CYP19A1), and 11ß-hydroxysteroid dehydrogenase type 1 (HSD11B1). Morphological analysis showed that severe impairment of the bone micro-architecture in OVX rats could be improved by TBD administration. The TBD-treated rats had a significantly lower bone surface-to-tissue volume (BS/TV) and a significantly smaller trabecular separation (Tb·Sp.) (P<0.05) than the OVX rats; in contrast, bone volume fraction (BVF), trabecular thickness (Tb·Th.), trabecular number (Tb·N.), and bone mineral density (BMD) were significantly higher in the TBD-treated rats (P<0.05). Multivariate and univariate analysis showed that OVX resulted in significant alterations in the concentrations of 105 metabolites and 11 metabolic pathways (P<0.05); in addition, 26 potential biomarkers were identified to investigate the progression of PMOP. Network pharmacology showed that major alterations in vitamin B6 metabolism were associated with the VDR target. Next, we validated the three crucial targets (VDR [P<0.01], HSD11B1 [P<0.01], and CYP19A1 [P<0.05]) by enzyme-linked immunosorbent assays (ELISAs) and demonstrated that the levels of these targets were elevated in the OVX group but reduced in the TBD-treatment group. Collectively, our results suggest that the interventional effects of TBD on OVX rats are likely to be associated with the down regulation of VDR. Our findings enhance our molecular understanding of the interventional effects of TBD on PMOP and will allow us to develop further TBD studies.

17.
J Sep Sci ; 43(18): 3702-3713, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32671897

RESUMEN

Tabson-2 decoction is the traditional Mongolian formula for anti-osteoporosis, and the ambiguous of active ingredient is an important factor in restricting its modernization and globalization. Although pharmacokinetic profiles research is a viable approach to find the components being responsible for formula efficacy, the pharmacokinetics study of Tabson-2 decoction has not been elucidated yet. Owing to the existence of isomers, low bioavailability of some small molecule and interference of endogenous, the pharmacokinetics study of Tabson-2 decoction are more difficult than that of chemical drugs. In our experiment, a specific and sensitive liquid chromatography-tandem mass spectrometry method was developed and validated for simultaneous determination of 16 active ingredients in Tabson-2 decoction, which could fulfill the requirements of multi-compounds pharmacokinetic study of Tabson-2 decoction. Additionally, the ingredients with significant distributions in rats were gentianic acid, chlorogenic acid, and aucubin, which could be the main potential active components in Tabson-2 decoction. The components with a significant bioavailability difference between normal and d-galactose induced osteoporosis rats were achieved as well. These data offer useful information for screening the active ingredients in Tabson-2 decoction, and assessing the bioavailability of these active ingredients in different physiological status, which might provide a possible mechanism of anti-osteoporosis efficacy of Tabson-2 decoction.


Asunto(s)
Medicamentos Herbarios Chinos/farmacocinética , Osteoporosis/tratamiento farmacológico , Animales , Cromatografía Líquida de Alta Presión , Medicamentos Herbarios Chinos/química , Galactosa , Masculino , Estructura Molecular , Osteoporosis/inducido químicamente , Ratas , Ratas Wistar , Espectrometría de Masas en Tándem
18.
Pharmacology ; 105(11-12): 669-680, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32694254

RESUMEN

OBJECTIVE: An integrated TK-TD model with indirect response to toxicity was established using ADAPT 5 to evaluate abnormal heart rate (HR) and QT interval changes caused by Radix Aconitikusnezoffii (RAK). METHODS: Plasma samples were collected from male SD rats, which were divided into the blank and RAK groups. HR and QT interval indicators were recorded. Four alternative TK models were analyzed, and the best fitting model was determined. An indirect toxicodynamics model was selected, and the relationship of plasma concentration-time-toxicity was linked by Hill's equation. RESULTS: A 1-compartment linear first-order elimination kinetic model with the biophase model - an indirect toxic effect response model - best described the data. The high-dose QT interval was evaluated. Model simulation with the ML method showed that the fitting values of 0-15 h all fell within the confidence interval (95%). AMOS analysis showed that almost all the load factor of the variable was >0.7, and the χ2 value was 4.169 indicating a significant difference. Load factor (correlation coefficient) between the HR and QT intervals was -0.965, indicating negative correlation. CONCLUSIONS: The integrated TK-TD model with linear atrioventricular first-order elimination kinetics and indirect response represents a novel mathematical method to evaluate drug-induced changes in HR and QT.


Asunto(s)
Aconitum/toxicidad , Aconitum/química , Animales , Electrocardiografía/efectos de los fármacos , Sistema de Conducción Cardíaco/efectos de los fármacos , Frecuencia Cardíaca/efectos de los fármacos , Masculino , Modelos Biológicos , Ratas Sprague-Dawley , Programas Informáticos , Pruebas de Toxicidad , Toxicocinética
19.
J Ethnopharmacol ; 260: 113018, 2020 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-32502650

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Echinops latifolius Tausch (ELT) is traditional Mongolian medicine in China, and often used to against osteoporosis, strengthen tendons and bones, clear bones heat. AIM OF THE STUDY: To study efficacy of ELT on ovariectomized (OVX) rats and underly metabolic pathways related to trabecular micro-architecture changing of OVX. MATERIALS AND METHODS: Three-month-old female Wistar rats were randomly divided into 4 groups (n = 6) including normal group (without surgery), sham group (bilateral laparotomy), OVX group (bilateral ovariectomy), and ELT-treated groups (ELT-treated after bilateral ovariectomy). The effects of ELT on trabecular micro-architecture and biochemical markers of OVX rat were investigated by dual-energy X-ray absorptiometry machine and Enzyme-linked immunosorbent assay (ELISA), respectively. Untargeted metabolomics strategy was applied to discover the potential biomarkers and related metabolic pathways involving the progression of OVX-induced osteoporosis. RESULTS: The trabecular micro-architecture and biochemical markers of OVX rats were improved by ELT. We found 36 potential biomarkers and 21 related metabolic pathways were involved in progression of OVX-induced osteoporosis. Amino acids metabolism and glycerophospholipids metabolism were mainly intervened in ELT treatment on ovariectomized rats. The disordered amino acids and glycerophospholipids metabolism closely related to the imbalance between bone resorption and formation were reversed by administration of ELT, indicating that the influences of ELT on OVX rats' trabecular micro-architecture may possible be associated with intervening amino acids and glycerophospholipids metabolism. CONCLUSIONS: This approach may provide the metabolomic perspective to link metabolic alterations and anti-osteoporosis action of ELT, to further explain how ELT works in postmenopausal patients with bone loss.


Asunto(s)
Echinops (Planta)/química , Metabolómica , Osteoporosis Posmenopáusica/tratamiento farmacológico , Extractos Vegetales/farmacología , Aminoácidos/metabolismo , Animales , Biomarcadores/metabolismo , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Femenino , Glicerofosfolípidos/metabolismo , Humanos , Medicina Tradicional China , Osteoporosis Posmenopáusica/metabolismo , Osteoporosis Posmenopáusica/patología , Ovariectomía , Ratas , Ratas Wistar
20.
RSC Adv ; 10(61): 37463-37472, 2020 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-35521233

RESUMEN

A chalcone, which is composed of two aromatic rings bridged by an α,ß-unsaturated carbonyl group, exhibits a variety of biological activities. With an objective to develop a novel chalcone-based functional dye, we have synthesized a chalcone diol CLN1, bearing two OH groups at the 2-positions on both phenyl rings, as well as reference compounds CLN2-6, and found that it serves as color indicators for pH and fluoride ions. CLN1 showed a vivid color change from colorless to yellow (halochromism) in water at pH ≥ 10. Furthermore, it presented a selective color change from colorless to red upon the addition of TBAF in an organic solvent such as CH3CN. CLN1 provided a strong red-shifted absorption band in the visible region under alkaline conditions in water and upon the addition of TBAF in CH3CN. The absorption spectral study together with TD-DFT calculations and X-ray crystallographic analysis revealed that the characteristic π-resonant structures of CLN1 caused by the ionization or OH-F- interactions and the planar conformation due to its intramolecular hydrogen bonding may provide a strong charge transfer (CT) absorption in the visible region.

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