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1.
Chin Med ; 19(1): 98, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39010069

RESUMO

BACKGROUND: Heart failure (HF) is a complex cardiovascular syndrome with high mortality. Santalum album L. (SAL) is a traditional Chinese medicine broadly applied for various diseases treatment including HF. However, the potential active compounds and molecular mechanisms of SAL in HF treatment are not well understood. METHODS: The active compounds and possible mechanisms of action of SAL were analyzed and validated by a systems pharmacology framework and an ISO-induced mouse HF model. RESULTS: We initially confirmed that SAL alleviates heart damage in ISO-induced HF model. A total of 17 potentially active components in SAL were identified, with Luteolin (Lut) and Syringaldehyde (SYD) in SAL been identified as the most effective combination through probabilistic ensemble aggregation (PEA) analysis. These compounds, individually and in their combination (COMB), showed significant therapeutic effects on HF by targeting multiple pathways involved in anti-oxidation, anti-inflammation, and anti-apoptosis. The active ingredients in SAL effectively suppressed inflammatory mediators and pro-apoptotic proteins while enhancing the expression of anti-apoptotic factors and antioxidant markers. Furthermore, the synergistic effects of SAL on YAP and PI3K-AKT signaling pathways were further elucidated. CONCLUSIONS: Mechanistically, the anti-HF effect of SAL is responsible for the synergistic effect of anti-inflammation, antioxidation and anti-apoptosis, delineating a multi-targeted therapeutic strategy for HF.

2.
Nat Prod Res ; : 1-7, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38988300

RESUMO

A new pair of butylphthalide diastereomers, dangguinolide A (1) and dangguinolide B (2), together with two known butylphthalide were isolated from Angelica sinensis. Their structures were determined by extensive spectroscopic analyses, and the absolute configurations of 1 and 2 were assigned via NMR calculations and ECD calculations. Their anti-inflammatory activities have evaluated in vitro.

3.
Inorg Chem ; 63(29): 13546-13557, 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-38976837

RESUMO

Hybrid copper(I) halides have garnered a significant amount of attention as potential substitutes in luminescence and scintillation applications. Herein, we report the discovery and crystal growth of new zero-dimensional compounds, (C2H8N)3Cu2I5 and (C2H8N)4Cu2Br6. The bromide and iodide have a triclinic structure with space group P1̅ and an orthorhombic structure with space group Pnma, respectively. (C2H8N)3Cu2I5 exhibits cyan emission peaking at 504 nm with a photoluminescence quantum yield (PLQY) of 34.79%, while (C2H8N)4Cu2Br6 shows yellowish-green emission peaking at 537 nm with a PLQY of 38.45%. The temperature-dependent photoluminescence data of both compounds were fitted to theoretical models, revealing that nonradiative intermediate states significantly affect thermal quenching and antiquenching. Electron-phonon interactions, the origin of emission line width broadening and peak shifting, were also investigated via fittings. The scintillation properties of (C2H8N)3Cu2I5 were evaluated, and an X-ray imaging device was successfully fabricated using (C2H8N)3Cu2I5. This work demonstrates the potentiality of copper halides in lighting and X-ray imaging applications.

5.
Int Immunopharmacol ; 136: 112383, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-38843642

RESUMO

The treatment of autoimmune and inflammatory diseases often requires targeting multiple pathogenic pathways. KYS202004A is a novel bispecific fusion protein designed to antagonize TNF-α and IL-17A, pivotal in the pathophysiology of autoimmune and inflammatory diseases. Our initial efforts focused on screening for optimal structure by analyzing expression levels, purity, and binding capabilities. The binding affinity of KYS202004A to TNF-α and IL-17A was evaluated using SPR. In vitro, we assessed the inhibitory capacity of KYS202004A on cytokine-induced CXCL1 expression in HT29 cells. In vivo, its efficacy was tested using a Collagen-Induced Arthritis (CIA) model in transgenic human-IL-17A mice and an imiquimod-induced psoriasis model in cynomolgus monkeys. KYS202004A demonstrated significant inhibition of IL-17A and TNF-α signaling pathways, outperforming the efficacy of monotherapeutic agents ixekizumab and etanercept in reducing CXCL1 expression in vitro and ameliorating disease markers in vivo. In the CIA model, KYS202004A significantly reduced clinical symptoms, joint destruction, and serum IL-6 concentrations. The psoriasis model revealed that KYS202004A, particularly at a 2  mg/kg dose, was as effective as the combination of ixekizumab and etanercept. This discovery represents a significant advancement in treating autoimmune and inflammatory diseases, offering a dual-targeted therapeutic approach with enhanced efficacy over current monotherapies.


Assuntos
Artrite Experimental , Interleucina-17 , Macaca fascicularis , Psoríase , Proteínas Recombinantes de Fusão , Fator de Necrose Tumoral alfa , Animais , Interleucina-17/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Humanos , Psoríase/tratamento farmacológico , Psoríase/imunologia , Psoríase/induzido quimicamente , Proteínas Recombinantes de Fusão/uso terapêutico , Proteínas Recombinantes de Fusão/farmacologia , Artrite Experimental/tratamento farmacológico , Artrite Experimental/imunologia , Camundongos , Quimiocina CXCL1/metabolismo , Quimiocina CXCL1/genética , Células HT29 , Doenças Autoimunes/tratamento farmacológico , Doenças Autoimunes/imunologia , Camundongos Transgênicos , Modelos Animais de Doenças , Anticorpos Biespecíficos/uso terapêutico , Anticorpos Biespecíficos/farmacologia , Masculino , Avaliação Pré-Clínica de Medicamentos , Imiquimode , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/farmacologia , Camundongos Endogâmicos DBA
6.
J Biotechnol ; 391: 106-116, 2024 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-38871028

RESUMO

Icaritin, a hydrolysate from total flavonoids of Epimedii (TFE), which has better anti-hepatoma activity than its glycosylated form. In this work, immobilized enzymes 4LP-Tpebgl3@Na-Y and DtRha@ES-107 were used to hydrolyze TFE to prepare icaritin. Five different hydrophobic deep eutectic solvents (HDES) were prepared and the most ideal HDES was successfully selected, which was composed of dodecyl alcohol and thymol with the molar ratio of 2:1. The relative enzyme activity of 4LP-Tpebgl3@Na-Y and DtRha@ES-107 was about 102.4 % and 112.5 %, respectively. In addition, the thermal and binding stability of 4LP-Tpebgl3@Na-Y and DtRha@ES-107 in HDES was not affected negatively. In the biphasic system composed of 50 % (v/v) HDES and Na2HPO4-citric acid buffer (50 mM, pH 5.5), 4LP-Tpebgl3@Na-Y (1.0 U/mL) and TFE (1 g/L) were reacted at 80 °C for 1 h, and then reacted with DtRha@ES-107 (20 U/mL) at 80 °C for 2 h. Finally, TFE was completely converted to 301.8 mg/L icaritin (0.82 mM). After 10 cycles, 4LP-Tpebgl3@Na-Y/DtRha@ES-107 still maintained 84.1 % original activity. In this study, we developed an efficient methodology for icaritin preparation through the integration of enzymatic catalysis and adsorption separation, presenting a viable approach for large-scale, cost-effective production of icaritin.


Assuntos
Biotransformação , Enzimas Imobilizadas , Flavonoides , Interações Hidrofóbicas e Hidrofílicas , Flavonoides/metabolismo , Flavonoides/química , Enzimas Imobilizadas/metabolismo , Enzimas Imobilizadas/química , Solventes Eutéticos Profundos/química , Solventes Eutéticos Profundos/metabolismo , Epimedium/química , Epimedium/metabolismo , Hidrólise , Solventes/química
7.
Phytomedicine ; 131: 155766, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38865935

RESUMO

BACKGROUND: Migraine is widely recognized as the third most prevalent medical condition globally. Tianshu capsule (TSC), derived from "Da Chuan Xiong Fang" of the Jin dynasty, is integral in the clinical treatment of migraine. However, the chemical properties and therapeutic mechanisms of TSC different portions remain unclear. PURPOSE: This study was designed to investigate the effects of TSC different portions (including small molecular TSCP-SM and polysaccharides TSC-P) on migraine and explore the underlying mechanisms. STUDY DESIGN AND METHODS: First of all, migraine rats were established by nitroglycerin injection and treated with TSC, TSC-P, and TSC-SM. ELISA, qPCR, and immunofluorescence were used to evaluate the pharmacological effects on migraine rats. Secondly, UPLC-Q/TOF-MS and GC--MS were employed to detect the components of TSC-SM. PMP-HPLC, NMR, FT-IR, UV-Vis, AFM, and SEM were used for the chemical profiling of polysaccharides. Thirdly, the metabolic behavior profile of TSC-P was characterized by oral administrated fluorescence-labeled TSC-P and detected by NIRF imaging. Finally, the anti-migraine mechanisms were explored by determining the composition of gut microbiota, analyzing colonic short-chain fatty acids (SCFAs), and examining serum tryptophan-related metabolites. RESULTS: Both small molecules (45 volatiles and 114 small molecules) and polysaccharides (including Glc, Ara, Gal, and Gal A) have exhibited effectiveness in alleviating migraine, and this efficacy is associated with reduced CGRP and iNOS levels, along with increased ß-EP expressions. Further mechanistic exploration revealed that small-molecules exhibited effectiveness in migraine treatment by exerting antioxidative actions, while polysaccharides demonstrated superior therapeutic effects in regulating 5-HT levels. By monitoring the metabolic behavior of polysaccharides with fluorescent labeling, it was observed that TSC-P exhibited poor absorption. Instead, TSC-P demonstrated its therapeutic effects by modulating the aberrations in gut microbiota (including Alloprevotella, Muribaculaceae_ge, and Ruminococcaceae_UCG-005), cecum short-chain fatty acids (such as isobutyric, isovaleric, and valeric acids), and serum tryptophan-related metabolites (including indole-3-acetamide, tryptophol, and indole-3-propionic acid). CONCLUSION: This research provides innovative insights into chemical composition, metabolic behavior, and proposed anti-migraine mechanisms of TSC from a polarity-based perspective, and pioneering an exploration focused on the polysaccharide components within TSC for the first time.


Assuntos
Medicamentos de Ervas Chinesas , Transtornos de Enxaqueca , Polissacarídeos , Ratos Sprague-Dawley , Transtornos de Enxaqueca/tratamento farmacológico , Animais , Masculino , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/química , Ratos , Polissacarídeos/farmacologia , Polissacarídeos/química , Modelos Animais de Doenças , Cápsulas
8.
J Cardiothorac Surg ; 19(1): 335, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38898495

RESUMO

BACKGROUND: Perioperative management and cardiac surgery in pregnant women with anti-phospholipid syndrome combined with heart valve disease have been rarely reported. CASE PRESENTATION: We describe a case of transcatheter mitral valve-in-valve replacement in a pregnant woman with bioprosthetic valve failure and anti-phospholipid syndrome at 18 weeks' gestation. The patient underwent a cesarean section delivery at 34 weeks of gestation, resulting in the birth of a healthy baby. CONCLUSIONS: Transapical mitral valve-in-valve surgery resulted in safe maternal and infant outcomes in a pregnant woman with anti-phospholipid syndrome combined with mitral bioprosthetic valve failure. The success of this procedure underscored the importance of multidisciplinary teamwork.


Assuntos
Síndrome Antifosfolipídica , Bioprótese , Implante de Prótese de Valva Cardíaca , Valva Mitral , Complicações Cardiovasculares na Gravidez , Humanos , Feminino , Gravidez , Síndrome Antifosfolipídica/complicações , Valva Mitral/cirurgia , Adulto , Implante de Prótese de Valva Cardíaca/métodos , Complicações Cardiovasculares na Gravidez/cirurgia , Próteses Valvulares Cardíacas , Cesárea , Cateterismo Cardíaco/métodos , Insuficiência da Valva Mitral/cirurgia , Falha de Prótese
9.
Biomed Pharmacother ; 176: 116908, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38850668

RESUMO

Non-alcoholic fatty liver disease (NAFLD), particularly advanced non-alcoholic steatohepatitis (NASH), leads to irreversible liver damage. This study investigated the therapeutic effects and potential mechanism of a novel extract from traditional Chinese medicine Alisma orientale (Sam.) Juzep (AE) on free fatty acid (FFA)-induced HepG2 cell model and high-fat diet (HFD) + carbon tetrachloride (CCl4)-induced mouse model of NASH. C57BL/6 J mice were fed a HFD for 10 weeks. Subsequently, the mice were injected with CCl4 to induce NASH and simultaneously treated with AE at daily doses of 50, 100, and 200 mg/kg for 4 weeks. At the end of the treatment, animals were fasted for 12 h and then sacrificed. Blood samples and liver tissues were collected for analysis. Lipid profiles, oxidative stress, and histopathology were examined. Additionally, a polymerase chain reaction (PCR) array was used to predict the molecular targets and potential mechanisms involved, which were further validated in vivo and in vitro. The results demonstrated that AE reversed liver damage (plasma levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), hepatocyte ballooning, hepatic steatosis, and NAS score), the accumulation of hepatic lipids (TG and TC), and oxidative stress (MDA and GSH). PCR array analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that AE protects against NASH by regulating the adipocytokine signaling pathway and influencing nuclear receptors such as PPARα. Furthermore, AE increased the expression of peroxisome proliferator-activated receptor gamma coactivator-1α (PPARGC1α) and reversed the decreased expression of PPARα in NASH mice. Moreover, in HepG2 cells, AE reduced FFA-induced lipid accumulation and oxidative stress, which was dependent on PPARα up-regulation. Overall, our findings suggest that AE may serve as a potential therapeutic approach for NASH by inhibiting lipid accumulation and reducing oxidative stress specifically through the PPARα pathway.


Assuntos
Alisma , Dieta Hiperlipídica , Hepatopatia Gordurosa não Alcoólica , Extratos Vegetais , Transdução de Sinais , Animais , Humanos , Masculino , Camundongos , Alisma/química , Tetracloreto de Carbono , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Células Hep G2 , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Extratos Vegetais/isolamento & purificação , PPAR alfa/metabolismo , Transdução de Sinais/efeitos dos fármacos
10.
Artigo em Inglês | MEDLINE | ID: mdl-38896509

RESUMO

Recommendation system (RS) is an important information filtering tool in nowadays digital era. With the growing concern on privacy, deploying RSs in a federated learning (FL) manner emerges as a promising solution, which can train a high-quality model on the premise that the server does not directly access sensitive user data. Nevertheless, some malicious clients can deduce user data by analyzing the uploaded model parameters. Even worse, some Byzantine clients can also send contaminated data to the server, causing blockage or failure of model convergence. In addition, most existing researches on federated recommendation algorithms only focus on unimodality learning, ignoring the assistance of multiple modality data to promote recommendation accuracy. Therefore, this article designs an FL-based privacy-preserving multimodal RS framework. To distinguish various modality data, an attention mechanism is introduced, wherein different weight ratios are assigned to various modal features. To further strengthen the privacy, local differential privacy (LDP) and personalized FL strategies are designed to identify malicious clients and bolster the resilience against Byzantine attacks. Finally, two multimodal datasets are established to verify the effectiveness of the proposed algorithm. The superiority of our proposed techniques is confirmed by the simulation results.

11.
Food Chem ; 457: 140123, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38917562

RESUMO

A magnetic biochar nanomaterial derived from fungal hyphae was introduced into the sample preparation field. The magnetic fungal hyphae-derived biomass carbon (MFHBC) could be produced by a controllable hydrothermal method. In order to obtain the best sorbent for magnetic solid-phase extraction (MSPE), the reaction conditions containing temperature, time and the consumption of fungal hyphae were investigated. A series of MFHBC materials were characterized by vibrating sample magnetometers, X-ray photoelectron spectroscopy, Fourier transform infrared spectroscopy, and transmission electron microscopy. A material with a satisfactory saturation magnetization (21.58 emu g-1) and largest surface area (88.06 m2 g-1) was selected as the sorbent to extract ten typical organochlorine pesticides (OCPs). The extraction conditions were optimized as 20 mL of sample solution with 70 mg of sorbent and 2.0 g of NaCl oscillated at 50 °C for 5.0 min. And the optimum desorption was performed by oscillating sorbent in 1.0 mL acetonitrile for 5.0 min. Then, the MFHBC-based MSPE-GC-MS/MS methods were established for different samples including water samples, tea beverages, and Chinese traditional medicines. The linearities were 10-2500 ng L-1 or 100-25,000 ng kg-1, and the limits of detection were 0.3-13.9 ng L-1 for water sample, 0.1-9.7 ng L-1 for tea beverage samples, 0.1-21.4 ng L-1 for Shenqi Fuzheng injection samples, and 7.2-278.3 ng kg-1 for Astragali Radix decoction pieces. Except for satisfactory repeatability (RSDs ≤13.8%) in intra-day and inter-day tests (n = 3), the reproducibility (RSDs ≤13.5%, n = 3) of MFHBC was acceptable. The methods were applied in the determination of OCPs from above real samples, with the recoveries of 80.5-117.2% and the RSDs (n = 3) <8.9%. The methods were suitable in the sensitive determination of OCPs from simple to complex matrix samples.

12.
Zhongguo Zhong Yao Za Zhi ; 49(8): 2158-2168, 2024 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-38812231

RESUMO

This study systematically explored the transdermal diffusion law of functional substances of Jingu Zhitong Gel(JGZTG). The transdermal diffusion research methods of JGZTG were investigated by single factor trial with the automated transdermal(dry-heat) sampling system. High performance liquid chromatography(HPLC) content determination method was established to determine the contents of ferulic acid, senkyunolide I, cinnamic acid, hydroxy-ε-xanthoxylin, hydroxy-α-xanthoxylin, and hydroxy-ß-xanthoxylin in the transdermal diffusion solution of JGZTG. The transdermal diffusion law of the components within 16 h was investigated. The results showed that the optimal transdermal diffusion method of JGZTG was as follows: Rat skin was used as the transdermal barrier; normal saline was used as the receiving medium; the dosage of JGZTG was 0.3 g, and the receiving solution was extracted by ethyl acetate. The results of transdermal diffusion showed that the release of ferulic acid, cinnamic acid, and senkyunolide I increased significantly at 0-8 h and slowed down at 8-16 h. The drug release was a synergic process of diffusion and dissolution, in which ferulic acid and cinnamic acid followed Higuchi and Ritger-Peppas equations, and liguolactone I followed Higuchi equation. The transdermal diffusion curves of hydroxy-ε-zanthoxylin, hydroxy-α-zanthoxylin, and hydroxy-ß-zanthoxylin showed continuous release within 16 h, and the drug release was skeleton dissolution. The diffusion law followed zero-order equation, first-order equation, and Ritger-Peppas equation. In clonclusion, it is a controlled release of ferulic acid, ligustrone I, cinnamic acid, hydroxy-ε-pyrroxylin, hydroxy-α-pyrroxylin, and hydroxy-ß-pyrroxylin in JGZTG, which can maintain stable blood drug concentration with 16 h, and the cumulative transmittance of each component with 12 h can reach 80% of cumulative transmittance with 24 h, which is in line with the clinical drug use law of bis in die.


Assuntos
Medicamentos de Ervas Chinesas , Absorção Cutânea , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacocinética , Medicamentos de Ervas Chinesas/administração & dosagem , Ratos , Animais , Difusão , Administração Cutânea , Pele/metabolismo , Pele/química , Géis/química , Masculino , Ratos Sprague-Dawley , Cromatografia Líquida de Alta Pressão , Cinamatos/farmacocinética , Cinamatos/análise , Cinamatos/química , Ácidos Cumáricos/farmacocinética , Ácidos Cumáricos/análise
13.
Zhongguo Zhong Yao Za Zhi ; 49(8): 2262-2272, 2024 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-38812240

RESUMO

To investigate the effect of epimedium total flavone capsules on post-stroke cognitive impairment(PSCI) in rats. The transient middle cerebral artery occlusion(tMCAO) model was constructed on selected rats, and rats with impaired neurological function were randomly divided into the model group, low, middle, and high dose groups of epimedium total flavone capsules, and nimodipine tablet group. The cognitive function of rats was measured after administration. Pathological changes in brain tissue were observed after hematoxylin-eosin staining(HE). Neuronal nuclei(NeuN) and glial fibrillary acidic protein(GFAP) distribution in brain tissue were tested by immunofluorescent staining. The level of amyloid beta 1-42(Aß_(1-42)), neuron specific enolase(NSE), acetylcholine(ACH), dopamine(DA), 5-hydroxytryptamine(5-HT), norepinephrine(NE), interleukin-1ß(IL-1ß), tumor necrosis factor-α(TNF-α), and hypersensitive C-reactive protein(hs-CRP) in rat serum was tested. Moreover, Western blot was utilized to test the expression of nuclear factor-kappaB(NF-κB), p-NF-κB, alpha inhibitor of NF-κB(IκBα) protein, and p-IκBα protein in the hippocampus. The experimental results showed that epimedium total flavone capsules can improve the cognitive function of model rats, and the mechanism may be related to the regulation of the expression of p-IκBα and p-NF-κB proteins, so as to inhibit inflammatory response induced by ischemia-reperfusion.


Assuntos
Cápsulas , Disfunção Cognitiva , Medicamentos de Ervas Chinesas , Epimedium , Flavonas , Ratos Sprague-Dawley , Acidente Vascular Cerebral , Animais , Ratos , Epimedium/química , Masculino , Flavonas/administração & dosagem , Flavonas/farmacologia , Flavonas/química , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/farmacologia , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/complicações , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/etiologia , Humanos , Peptídeos beta-Amiloides/metabolismo , NF-kappa B/metabolismo , NF-kappa B/genética , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Cognição/efeitos dos fármacos
14.
Artigo em Inglês | MEDLINE | ID: mdl-38782726

RESUMO

BACKGROUND AND HYPOTHESIS: Volenrelaxin, is a half-life-extended recombinant human relaxin protein developed for improving kidney perfusion and cardiorenal function. This study assessed the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of volenrelaxin following single- and multiple-ascending doses (SAD and MAD) administration. METHODS: In this Phase 1, 4-part, randomized, double-blinded, placebo-controlled SAD and MAD study in healthy participants, SAD participants (n = 56) received an intravenous (IV) or subcutaneous (SC) dose of volenrelaxin or placebo in a dose-ascending manner. MAD participants (n = 77) received volenrelaxin or placebo SC once weekly for 5 weeks. Effective renal plasma flow (ERPF) and measured glomerular filtration rate (mGFR) were determined by para-aminohippurate and iohexol clearance, respectively. RESULTS: Volenrelaxin demonstrated an extended half-life and increased acute and chronic placebo-adjusted ERPF change from baseline by 50% and 44%, respectively (p < 0.0001). Measured GFR was unchanged, while filtration fraction and afferent/efferent renal arteriolar resistances were reduced. Systolic and diastolic blood pressures decreased, and pulse rate increased with increasing volenrelaxin exposures, demonstrating maximal model-derived placebo-adjusted changes (90% confidence interval) of -6.16 (-8.04, -4.28) mmHg, -6.10 (-7.61, -4.58) mmHg, and + 4.39 (3.38, 5.39) bpm, respectively. Adverse events were mild, with no difference in orthostatic hypotension between volenrelaxin and placebo. CONCLUSION: Volenrelaxin was well-tolerated, safe and suitable for weekly SC dosing. Volenrelaxin showed a sustained improvement in kidney perfusion upon repeated dosing, supporting further clinical development in chronic kidney disease and chronic heart failure. Clinical trial registration: NCT04768855.

15.
Biol Pharm Bull ; 47(5): 978-987, 2024 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-38631865

RESUMO

Nonalcoholic steatohepatitis (NASH) is a subtype of nonalcoholic fatty liver disease (NAFLD) characterized by hepatic steatosis and evidence of hepatocyte injury (ballooning) and inflammation, with or without liver fibrosis. In this study, after 12 weeks of induction, the mice were treated with emodin succinyl ethyl ester (ESEE) for four weeks at doses of 10/30/90 mg/kg/d. The blood analysis of experimental endpoints showed that ESEE exhibited significant therapeutic effects on the progression of disorders of glycolipid metabolism and the induced liver injury in the model animals. Histopathological diagnosis of the liver and total triglyceride measurements revealed that ESEE had a significant therapeutic effect on the histopathological features of nonalcoholic fatty liver disease/hepatitis, such as cellular steatosis and activation of intrahepatic inflammation. Additionally, ESEE was able to improve hepatocyte fat deposition, steatosis, and the course of intrahepatic inflammatory activity. Furthermore, it showed some inhibitory effect on liver fibrosis in the model animals. In summary, this study confirms the therapeutic effects of ESEE on the NAFLD/NASH model in C57BL/6J mice induced by a high-fat, high cholesterol, and fructose diet. These effects were observed through improvements in liver function, inhibition of fibrosis, and inflammatory responses. Changes in blood glucose levels, blood lipid metabolism, liver histopathological staining, liver fibrosis staining, and related pathological scores further supported the therapeutic effects of ESEE. Therefore, this study has important implications for the exploration of novel drugs for nonalcoholic fatty liver disease.


Assuntos
Dieta Hiperlipídica , Emodina , Frutose , Fígado , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica , Animais , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/patologia , Hepatopatia Gordurosa não Alcoólica/etiologia , Masculino , Emodina/farmacologia , Emodina/uso terapêutico , Emodina/análogos & derivados , Fígado/efeitos dos fármacos , Fígado/patologia , Fígado/metabolismo , Dieta Hiperlipídica/efeitos adversos , Camundongos , Triglicerídeos/sangue , Colesterol/sangue , Modelos Animais de Doenças , Glicemia/efeitos dos fármacos
16.
J Sep Sci ; 47(5): e2300922, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38471974

RESUMO

Qi-Wei-Tong-Bi oral liquid (QWTB), a famous Chinese medicine preparation composed of seven crude drugs has a good therapeutic effect on rheumatoid arthritis and is widely used in China. However, its chemical composition and quality control have not been comprehensively and systematically investigated. In this study, high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was employed for its chemical profiling. As a result, 100 components were chemically characterized. Additionally, high-performance liquid chromatography coupled with a quadrupole linear ion trap mass spectrometry method was developed to simultaneously quantify nine bioactive components (hyperoside, ononin, quercetin, sinomenine, magnoflorine, gallic acid, protocatechuic acid, monotropein, and cyclo-(Pro-Tyr)) in multiple-reaction monitoring mode. After successful validation in terms of linearity, precision, repeatability, and recovery, the assay method was applied for the determination of 10 batches of QWTB. The results showed that QWTB was enriched in sinomenine and magnoflorine with the highest amount up to hundreds or even thousands of µg/mL, while quercetin, ononin, cyclo-(Pro-Tyr), and hyperoside were much lower with the lowest content below 10 µg/mL. This study work would help to reveal the chemical profiling and provide a valuable and reliable approach for quality evaluation and even pharmacodynamic material basis studies of QWTB.


Assuntos
Medicamentos de Ervas Chinesas , Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/análise , Flavonoides/análise , Espectrometria de Massa com Cromatografia Líquida , Quercetina/análise , Espectrometria de Massas em Tandem/métodos
17.
Front Cardiovasc Med ; 11: 1300508, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38468722

RESUMO

A totally endoscopic minimally invasive approach is widely used for cardiac valve surgery in normal adults. However, minimally invasive cardiac surgery during pregnancy is rarely reported. In addition to traditional median thoracotomy, totally endoscopic minimally invasive approaches can now be used for pregnant patients. We describe our experience with totally endoscopic cardiac valve surgery (TECVS) during pregnancy, which is safe for both mothers and fetuses.

18.
Artigo em Inglês | MEDLINE | ID: mdl-38421545

RESUMO

Quercetin, as a representative flavonoid, is widely present in daily diet and has been developed as a dietary supplement due to its beneficial physiological activities. However, the application of quercetin is limited due to its poor water solubility and extensive metabolism. So far, the nano-drug delivery systems designed to improve its bioavailability generally have the shortcomings of low drug loading content and difficulty in industrial production. In order to tackle these problems, quercetin supersaturated drug delivery system (QSDDS) was successfully prepared using solvent method, for which PVP K30 was employed as a crystallization and precipitation inhibitor to maintain the supersaturated state of quercetin in aqueous system. The obtained QSDDS, with a relative high drug loading content of 13%, could quickly disperse in water and form colloidal system with the mean particle size of about 200 nm, meanwhile induce the generation of supersaturated quercetin solution more than 12 h. In vivo pharmacokinetic study proved that QSDDS achieved a high absolute bioavailability of 36.05%, 10 times as that of physical quercetin suspension, which was dose-dependent with higher bioavailability at higher dose. Considering the simple preparation method, QSDDS provided a feasible strategy and a simple way to improve oral absorption of insoluble flavonoids.

19.
Zhongguo Zhong Yao Za Zhi ; 49(2): 403-411, 2024 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-38403316

RESUMO

Based on the concept of quality by design(QbD), this study optimized the processing technology of Ilicis Rotundae Cortex. According to the processing method and ingredient requirements of Ilicis Rotundae Cortex in the Chinese Pharmacopoeia, the content of syringin and pedunculoside, alcohol extract, fragmentation rate, and moisture content were taken as the critical quality attributes(CQAs). The soaking time, moistening time, and drying time were taken as critical process parameters(CPPs) by single factor tests. The weight coefficients of CQAs were determined by the analytic hierarchy process(AHP)-entropy weighting method, and the comprehensive score was calculated. With the comprehensive score as the response value, Box-Behnken design was employed to establish a mathematical model between CPPs and CQAs, and the design space for the processing of Ilicis Rotundae Cortex was built and verified. The results of ANOVA showed that the mathematical model had the P value below 0.05, the lack of fit greater than 0.05, adjusted R~2=0.910 5, and predicted R~2=0.831 0, which indicated that the proposed model had statistical significance and good prediction performance. Considering the factors in production, the best processing conditions of Ilicis Rotundae Cortex were decoction pieces of about 1 cm soaking for 1 h, moistening for 4 h, and drying at 60-70 ℃ in a blast drier for 2 h. The optimized processing technology of Ilicis Rotundae Cortex was stable and feasible, which can provide a reference for the standardized preparation and stable quality of Ilicis Rotundae Cortex.


Assuntos
Medicamentos de Ervas Chinesas , Casca de Planta , Tecnologia , Etanol
20.
RSC Adv ; 14(9): 6064-6071, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38370457

RESUMO

In petroleum, petrochemicals, metallurgy, and chemical industries, a significant volume of oily wastewater is unavoidably generated throughout the production processes. This not only harms the environment but also brings about diverse adverse effects on social and economic progress. In this study, copper mesh separation membranes exhibiting superhydrophobicity and superhydrophilicity/underwater superoleophobicity were fabricated through in situ oxidation, chemical vapor deposition, and other physical and chemical modification techniques. Moreover, copper meshes possessing contrasting wetting properties were incorporated into a system combining superhydrophilicity and superhydrophobicity enabling the continuous and efficient separation of mixed oil-water liquids. The separation efficiency of both the superhydrophobic and superhydrophilic membranes surpassed 99.0% and remained above 97.0% after 15 days of continuous use, showcasing the remarkable effectiveness and durability of the integrated system design. This research presents a straightforward and cost-effective design approach for the large-scale treatment of oily wastewater in industrial settings, which is expected to have extensive applications in practical production.

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