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1.
Nat Commun ; 14(1): 8386, 2023 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-38104122

RESUMO

Bioelectronic medicine is a rapidly growing field where targeted electrical signals can act as an adjunct or alternative to drugs to treat neurological disorders and diseases via stimulating the peripheral nervous system on demand. However, current existing strategies are limited by external battery requirements, and the injury and inflammation caused by the mechanical mismatch between rigid electrodes and soft nerves. Here we report a wireless, leadless, and battery-free ferroelectret implant, termed NeuroRing, that wraps around the target peripheral nerve and demonstrates high mechanical conformability to dynamic motion nerve tissue. As-fabricated NeuroRing can act as an ultrasound receiver that converts ultrasound vibrations into electrostimulation pulses, thus stimulating the targeted peripheral nerve on demand. This capability is demonstrated by the precise modulation of the sacral splanchnic nerve to treat colitis, providing a framework for future bioelectronic medicines that offer an alternative to non-specific pharmacological approaches.


Assuntos
Tecido Nervoso , Nervos Periféricos , Nervos Periféricos/fisiologia , Sistema Nervoso Periférico , Eletrodos , Próteses e Implantes
2.
J Agric Food Chem ; 71(48): 18877-18889, 2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-37991200

RESUMO

The development of products from natural plant sources, including agriculture and food wastes, contributes significantly to the circular economy and global sustainability. Cork and grape wastes were employed as the primary sources in this study to obtain compounds of interest under mild extraction conditions. Laccase was applied to oxidize the cork and grape extracts, with the aim of producing value-added molecules with improved properties. Ultraviolet-visible (UV-vis) spectroscopy was assessed to monitor the oxidation process, and characterization of the end products was performed by matrix-assisted laser desorption/ionization-time-of-flight (MALDI-TOF) spectroscopy. The antioxidant and antiaging properties were evaluated by means of ABTS, DPPH, FRAP, and SPF testing. Overall, as compared to their monomeric counterparts, the polymeric compounds displayed remarkable antioxidant and antiaging characteristics after laccase oxidation, showing tremendous potential for applications in the food, pharmaceutical, cosmetic, and textile industries.


Assuntos
Lacase , Vitis , Lacase/química , Polímeros , Vitis/química , Antioxidantes , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Catálise , Extratos Vegetais/química
3.
Front Microbiol ; 14: 1111468, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36778876

RESUMO

Secondary effluents contain considerable amounts of nitrogen and phosphorous, which if dumped untreated can cause eutrophication of the receiving water bodies. Microalgae can remove these nutrients and other pollutants from the wastewater effluents and play an effective role in the secondary effluent treatment. In this study, six microalgae strains (SNN1, SNN2, SNN3, SNN4, SNS1, and SNS2) were isolated and screened from the water and mud of Yingxue Lake of Shandong Jianzhu University, and their efficiencies for the removal of COD, NH4 +-N, TN, and TP in the secondary effluent were assessed. By comparing the growth performances and nutrient removal ability of algal strains in domestic sewage, we found that SNN1 (identified and named as Desmodesmus sp. SNN1) has the highest efficiency for biomass accumulation and sewage purification. Hence, the algal strain SNN1 was selected for further screening and optimization experiments. The strain showed higher biomass yield and better nutrient removal rate when the pH of secondary effluent was 9.0 and the initial inoculum concentration (optical density at 680 nm) of algal strain was 0.4. After 12 days of treatment, the concentrations of COD, NH4 +-N, TN, and TP in the secondary effluent were 31.79, 0.008, 8.631, and 0.069 mg/L, respectively. Therefore, SNN1 with the removal rates of 52.69% (COD), 99.99% (NH4 +-N), 89.09% (TN), and 94.64% (TP) displayed its high potential in nutrient removal. In addition, it also yielded 5.30 mg/L of chlorophyll a and 168.33 mg/L of lipids. These results demonstrated that this strain exhibited an effective treatment capacity for secondary effluent and microalgal oil production. This study is helpful to provide a strategy for the resource utilization of secondary effluent and the conservation of freshwater resources required by microalgae culture.

4.
Int J Biol Macromol ; 233: 123404, 2023 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-36706879

RESUMO

Polysaccharide-based materials with porous structure were selected as the basic skeleton to prepare a flexible and biodegradable wound dressing. The carboxymethyl chitosan/sodium alginate/tea polyphenols (CC/SA/TP) with a two-layer porous structure exhibits a variety of performances. The specific combined structure with ordered and lamellar porous structure was constructed by high-speed homogenized foaming, Ca2+ crosslinking and two-step freeze-drying methods. Moreover, the CC/SA/TP porous structure owns better shape retention and recovery because of the 3D network with an "egg-box" structure formed by impregnation. Tea polyphenols are efficiently encapsulated into a porous structure and released in a sustained pattern. After storing for 60 days, the CC/SA/TP porous structure still exhibits great suitable water vapor transmittance, efficient antibacterial activity and ultrarapid antioxidant activity. Meanwhile, the relatively low differential blood clotting index (BCI) and cytotoxicity of the CC/SA/TP porous structure indicate that it possesses the possibility of adjusting and controlling wound bleeding. The test results reveal that the CC/SA/TP porous structure might be expected to play a great potential role in biomedical applications of wound dressing.


Assuntos
Quitosana , Polifenóis , Polifenóis/farmacologia , Polifenóis/química , Alginatos/química , Quitosana/química , Chá/química , Porosidade , Antibacterianos/farmacologia , Antibacterianos/química , Bandagens
5.
Foods ; 12(23)2023 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-38231653

RESUMO

This study was conducted to evaluate the potential effects of dietary grape residue levels on the slaughter indicators, meat quality, meat shelf-life, unsaturated fatty acid content, and expression of fatty acid deposition genes in the muscle of lambs. Sixty 30-month-old male Dorper and Small-Tailed Han F1 hybrid lambs were assigned to a single factor complete randomized trial design and fed with four different diets including 0%, 8%, 16%, and 24% grape dregs, respectively. The findings regarding meat production efficacy in the lambs revealed substantial differences. The control group showed notably lower dressing percentage, carcass weight, net meat weight, meat percentage concerning carcass, meat-to-bone ratio, relative visceral and kidney fat mass, and rib eye area compared to the other groups (p < 0.05). Additionally, the meat shearing force of lambs fed a diet with 16% grape pomace (GP) was significantly higher than that of the 24% GP group (p < 0.05), while the 24 h meat color parameter a* value of the control group was notably higher than that of the 8% GP group (p < 0.05). In addition, compared to the control group, lambs fed with a diet containing 16% GP had higher levels of oleic acid (C18:1n-9c), linoleic acid (C18:2n-6c), behenic acid (C22:0), tricosanoic acid (C23:0), lignoceric acid (C24:0), and conjugated linoleic acid (CLA), at a ratio of ∑CLA/TFA, ∑n-6, ∑MUFA, and ∑PUFA in the longissimus dorsi muscle (p < 0.05), but the reverse case was applicable for Total Volatile Basic Nitrogen (TVB-N) content (p < 0.05). GP supplementation did not substantially affect the expression of stearoyl-CoA desaturase (SCD), peroxisome proliferator activated receptor alpha (PPARα), and peroxisome proliferator-activated receptor gamma (PPARγ) genes (p > 0.05). The findings indicated that incorporating grape dregs in the diets of fattening lambs leads to notable enhancements in meat production and the antioxidant capacity of lamb meat, and effectively extends the shelf life of the meat.

6.
Drug Des Devel Ther ; 16: 1847-1863, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35734366

RESUMO

Background: Endometrial cancer (EC) is one of the most common gynecological malignancies, especially in postmenopausal women. Echinacoside (ECH) is a major natural bioactive ingredient derived from Cistanches Herba and Echinacea that has a variety of pharmacological effects. However, the efficacy and the mechanism of ECH against EC have not been elucidated yet. Purpose: A compound-target-disease network was constructed to explore the potential targets and mechanism of ECH against EC. Molecular docking and in vitro experiments further verified the effect of ECH against EC. Methods: The potential targets of ECH against EC were retrieved from multiple public databases. Then, the protein-protein interaction (PPI) network was constructed to screen hub targets. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed to discover the potential mechanism. Molecular docking was utilized to verify the binding affinity between hub targets and ECH. Finally, in vitro experiments were conducted to demonstrate the anti-EC effect of ECH. Results: A total of 110 genes were identified as potential targets of ECH against EC. The GO enrichment analysis found that targets were primarily related to oxygen species, apoptosis, and other physiological processes. KEGG pathway analysis showed that PI3K/Akt signaling pathways might play an important role in ECH against EC. Molecular docking indicated that ECH had a significant binding ability with the EGFR, AKT1, ESR1, CASP3, HSP90AA1and MMP9 targets. Results from in vitro experiments revealed that ECH induced apoptosis of Ishikawa and HEC-1-B cells by promoting the arrest of the G2M phase, increasing ROS levels, and decreasing mitochondrial membrane potential (MMP) levels. Furthermore, treatment of ECH significantly reduced the expression levels of PI3K and p-AKT, and the combination of the PI3K inhibitor (LY294002) further enhanced the effects of ECH against EC. The findings suggested that ECH exerted an inhibitory effect on EC cells by inhibiting the PI3K/AKT pathway. Conclusion: Based on network pharmacology, molecular docking technology and in vitro experiments, we comprehensively clarified the anti-EC efficacy of ECH through multiple targets and signal pathways. Furthermore, we provided a novel idea of Traditional Chinese medicine (TCM) against EC.


Assuntos
Medicamentos de Ervas Chinesas , Neoplasias do Endométrio , Medicamentos de Ervas Chinesas/química , Neoplasias do Endométrio/tratamento farmacológico , Feminino , Glicosídeos , Humanos , Medicina Tradicional Chinesa/métodos , Simulação de Acoplamento Molecular , Farmacologia em Rede , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt/metabolismo
7.
Comput Intell Neurosci ; 2022: 8112375, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35310583

RESUMO

Goal. Stroke patients are usually accompanied by motor dysfunction, which greatly affects daily life. Electroacupuncture is a kind of nondrug therapy that can effectively improve motor function. However, the effect of electroacupuncture is hard to be measured immediately in clinic. This paper is aimed to reveal the instant changes in brain activity of three groups of stroke patients before, during, and after the electroacupuncture treatment by the EEG analysis in the alpha band and beta band. Methods. Seven different functional connectivity indicators including Pearson correlation coefficient, spectral coherence, mutual information, phase locking value, phase lag index, partial directed coherence, and directed transfer function were used to build the BCI-based brain network in stroke patients. Results and Conclusion. The results showed that the brain activity based on the alpha band of EEG decreased after the electroacupuncture treatment, while in the beta band of EEG, the brain activity decreased only in the first two groups. Significance. This method could be used to evaluate the effect of electroacupuncture instantly and quantitatively. The study will hopefully provide some neurophysiological evidence of the relationship between changes in brain activity and the effects of electroacupuncture. The study of BCI-based brain network changes in the alpha and beta bands before, during, and after electroacupuncture in stroke patients of different periods is helpful in adjusting and selecting the electroacupuncture regimens for different patients. The trial was registered on the Chinese clinical trial registry (ChiCTR2000036959).


Assuntos
Interfaces Cérebro-Computador , Eletroacupuntura , Acidente Vascular Cerebral , Encéfalo , Eletroencefalografia/métodos , Humanos , Acidente Vascular Cerebral/terapia
8.
Acta Pharmacol Sin ; 43(2): 470-482, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33850276

RESUMO

Aerobic glycolysis, also known as the Warburg effect, is a hallmark of cancer cell glucose metabolism and plays a crucial role in the activation of various types of immune cells. Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) catalyzes the conversion of D-glyceraldehyde 3-phosphate to D-glycerate 1,3-bisphosphate in the 6th critical step in glycolysis. GAPDH exerts metabolic flux control during aerobic glycolysis and therefore is an attractive therapeutic target for cancer and autoimmune diseases. Recently, GAPDH inhibitors were reported to function through common suicide inactivation by covalent binding to the cysteine catalytic residue of GAPDH. Herein, by developing a high-throughput enzymatic screening assay, we discovered that the natural product 1,2,3,4,6-penta-O-galloyl-ß-D-glucopyranose (PGG) is an inhibitor of GAPDH with Ki = 0.5 µM. PGG blocks GAPDH activity by a reversible and NAD+ and Pi competitive mechanism, suggesting that it represents a novel class of GAPDH inhibitors. In-depth hydrogen deuterium exchange mass spectrometry (HDX-MS) analysis revealed that PGG binds to a region that disrupts NAD+ and inorganic phosphate binding, resulting in a distal conformational change at the GAPDH tetramer interface. In addition, structural modeling analysis indicated that PGG probably reversibly binds to the center pocket of GAPDH. Moreover, PGG inhibits LPS-stimulated macrophage activation by specific downregulation of GAPDH-dependent glucose consumption and lactate production. In summary, PGG represents a novel class of GAPDH inhibitors that probably reversibly binds to the center pocket of GAPDH. Our study sheds new light on factors for designing a more potent and specific inhibitor of GAPDH for future therapeutic applications.


Assuntos
Gliceraldeído-3-Fosfato Desidrogenases/antagonistas & inibidores , Taninos Hidrolisáveis/farmacologia , Animais , Avaliação Pré-Clínica de Medicamentos/métodos , Glucose/metabolismo , Gliceraldeído-3-Fosfato Desidrogenase (Fosforiladora)/antagonistas & inibidores , Humanos , Espectrometria de Massa com Troca Hidrogênio-Deutério , Ácido Láctico/metabolismo , Espectroscopia de Ressonância Magnética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Compostos Organometálicos , Reação em Cadeia da Polimerase em Tempo Real
9.
EMBO Rep ; 23(2): e53499, 2022 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-34882936

RESUMO

The activation of the nucleotide oligomerization domain (NOD)-like receptor (NLR) family, pyrin domain-containing protein 3 (NLRP3) inflammasome is related to the pathogenesis of a wide range of inflammatory diseases, but drugs targeting the NLRP3 inflammasome are still scarce. In the present study, we demonstrated that Licochalcone B (LicoB), a main component of the traditional medicinal herb licorice, is a specific inhibitor of the NLRP3 inflammasome. LicoB inhibits the activation of the NLRP3 inflammasome in macrophages but has no effect on the activation of AIM2 or NLRC4 inflammasome. Mechanistically, LicoB directly binds to NEK7 and inhibits the interaction between NLRP3 and NEK7, thus suppressing NLRP3 inflammasome activation. Furthermore, LicoB exhibits protective effects in mouse models of NLRP3 inflammasome-mediated diseases, including lipopolysaccharide (LPS)-induced septic shock, MSU-induced peritonitis and non-alcoholic steatohepatitis (NASH). Our findings indicate that LicoB is a specific NLRP3 inhibitor and a promising candidate for treating NLRP3 inflammasome-related diseases.


Assuntos
Chalconas , Inflamassomos , Animais , Chalconas/farmacologia , Inflamassomos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Quinases Relacionadas a NIMA/genética , Quinases Relacionadas a NIMA/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR
10.
Artigo em Inglês | MEDLINE | ID: mdl-34956384

RESUMO

Herba Epimedii is a famous Chinese herbal medicine for treating bone diseases. Icariin and icariside II, the main chemical constituents, have attracted great attention from scientists for their potential as antiosteoporosis agents. Our study aimed to evaluate their effects on the lineage commitment of multipotential stromal cells (MSCs). The osteogenesis and adipogenesis of MSCs were assessed by ALP activity, calcium deposition, and adipocyte formation. The expression profiles and levels of osteogenic and adipogenic specific genes were evaluated by cDNA microarray and quantitative real-time PCR. The involvement of extracellular signal-regulated kinase (ERK) signaling was studied by enzyme-linked immunosorbent assay. Icariin and icariside II significantly increased ALP activity and mineralization during osteogenic differentiation of MSCs. Runx2, Col1, and Bmp2 were upregulated in the presence of icariin and icariside II. Meanwhile, they downregulated Pparg, Adipsin, and Cebpb expression during adipogenic differentiation. cDNA microarray revealed 57 differentially expressed genes during lineage commitment of MSCs. In addition, icariin and icariside II enhanced the phosphorylation of ERK, and the above biological effects were blocked by ERK inhibitor U0126. Icariin and icariside II may drive the final lineage commitment of MSCs towards osteogenesis and inhibit adipogenesis through the ERK signaling pathway. Both of them exert multiple osteoprotective effects and deserve more attention for their medicinal and healthcare prospects.

11.
Chemosphere ; 284: 131259, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34192664

RESUMO

Municipal wastewater is a very unique pool full of energy and useful substances. Though the innovative integrated anaerobic membrane bioreactor and reverse osmosis-ion exchange (AnMBR-RO-IE) process can produce high-grade reclaimed water with high energy efficiency, phosphorus resources recovery in the WWTPs has been rarely reported thus far. This study evaluated the feasibility of a phosphorus recovery batch reactor (PRBR) as an approach for the phosphate production from the P-enriched brine from AnMBR-RO-IE. With operating PRBR for 162 cycles, high to 85% of P recovery rate was obtained for 145 cycles, leading to a P production rate of 6.17 g/m3 domestic wastewater with nano-sorbents (NSs) consumption rate of 10.2 g/m3. Acidification pretreatment efficiently improved the adsorption capacity and reduced the NSs renewing frequency. High adsorption selectivity of NSs contributed to low impurities (<0.3%) in the P-enriched reclaimed solution. Moreover, the integrated AnMBR-RO-IE-PRBR process saved 47% of energy consumption compared to the present NEWater production process in Singapore. The innovative PRBR reactor was competitive compared to the commonly-used chemical precipitation methods in conventional WWTPs in terms of phosphorus recovery/loss and energy balance. It is expected that the proposed integrated process can offer new insights into the direction of phosphorus reclamation in the future WWTPs.


Assuntos
Águas Residuárias , Purificação da Água , Reatores Biológicos , Membranas Artificiais , Fosfatos , Fósforo , Sais , Eliminação de Resíduos Líquidos , Águas Residuárias/análise
12.
J Cardiovasc Pharmacol ; 77(4): 458-469, 2021 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-33657052

RESUMO

ABSTRACT: Chronic stable angina (CSA) is caused by coronary atherosclerosis. The gut microbiota (GM) and their metabolite trimethylamine-N-oxide (TMAO) levels are associated with atherosclerosis. Danlou tablet (DLT) combined with Salvia miltiorrhiza ligustrazine (SML) injection has been used to treat CSA. This study aims to investigate how DLT combined with SML (DLT-SML) regulates serum lipids, inflammatory cytokines, GM community, and microbial metabolite in patients with CSA. In this study, 30 patients with CSA were enrolled in the DLT-SML group, and 10 healthy volunteers were included in the healthy control group. The patients in the DLT-SML group were subdivided as the normal total cholesterol (TC) group and high-TC group according to their serum TC level before treatment. Blood samples were collected to investigate the (1) lipid content, including triglyceride (TG), TC, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol, (2) fasting blood glucose (Glu), (3) inflammatory cytokines, including interleukin-1 beta (IL-1ß), interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor-α (TNF-α), and (4) gut-derived metabolite, including lipopolysaccharides and TMAO level. GM composition was analyzed by sequencing 16S rRNA of fecal samples. Results showed that DLT-SML significantly decreased serum TG, TC, low-density lipoprotein cholesterol, IL-1ß, TNF-α, and TMAO levels of patients with CSA. DLT-SML increased the abundance of Firmicutes and decreased Proteobacteria, which were significantly lower or higher in patients with CSA, respectively, compared with the healthy control group. In particular, DLT-SML increased the microbial diversity and decreased Firmicutes/Bacteroidetes ratio of patients with high-TC. The abundance of Sarcina, Anaerostipes, Streptococcus, Weissella, and Erysipelatoclostridium was decreased, whereas Romboutsia, Faecalibacterium, and Subdoligranulum were increased by DLT-SML treatment in patients with CSA. These findings indicated that DLT-SML improved patients with CSA by ameliorating dyslipidemia profile, decreasing the circulating inflammatory cytokines, and regulating the GM composition and their metabolites.


Assuntos
Angina Estável/tratamento farmacológico , Anti-Inflamatórios/uso terapêutico , Bactérias/efeitos dos fármacos , Medicamentos de Ervas Chinesas/uso terapêutico , Dislipidemias/tratamento farmacológico , Microbioma Gastrointestinal/efeitos dos fármacos , Hipolipemiantes/uso terapêutico , Inflamação/tratamento farmacológico , Pirazinas/uso terapêutico , Adulto , Idoso , Angina Estável/sangue , Angina Estável/diagnóstico , Angina Estável/microbiologia , Anti-Inflamatórios/efeitos adversos , Bactérias/metabolismo , Biomarcadores/sangue , China , Citocinas/sangue , Quimioterapia Combinada , Medicamentos de Ervas Chinesas/efeitos adversos , Disbiose , Dislipidemias/sangue , Dislipidemias/diagnóstico , Feminino , Humanos , Hipolipemiantes/efeitos adversos , Inflamação/sangue , Inflamação/diagnóstico , Mediadores da Inflamação/sangue , Lipídeos/sangue , Masculino , Metilaminas/metabolismo , Pessoa de Meia-Idade , Pirazinas/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
13.
Food Funct ; 12(4): 1482-1497, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33502415

RESUMO

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. The prognosis of HCC is very poor due to the absence of symptoms and a lack of effective treatments. Studies have shown that various Foeniculum vulgare (fennel) extracts exhibit anti-cancer effects on malignant tumors such as skin cancer and prostate cancer. However, the anti-tumor activity of Foeniculum vulgare and its underlying molecular mechanisms towards HCC are unknown. Here, we provide fundamental evidence to show that the 75% ethanol extract of Foeniculum vulgare seeds (FVE) reduced cell viability, induced apoptosis, and effectively inhibited cell migration in HCC cells in vitro. HCC xenograft studies in nude mice showed that FVE significantly inhibited HCC growth in vivo. Mechanistic analyses showed that FVE reduced survivin protein levels and triggered mitochondrial toxicity, subsequently inducing caspase-3 activation and apoptosis. Survivin inhibition effectively sensitized HCC cells to FVE-induced apoptosis. Moreover, FVE did not induce a decrease in survivin or apoptotic toxicity in normal liver cells. Collectively, in vivo and in vitro results suggest that FVE exerts inhibitory effects in HCC by targeting the oncoprotein survivin, suggesting FVE may be a potential anti-cancer agent that may benefit patients with HCC.


Assuntos
Carcinoma Hepatocelular/metabolismo , Foeniculum/química , Neoplasias Hepáticas/metabolismo , Extratos Vegetais/farmacologia , Idoso , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Feminino , Humanos , Masculino , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Sementes/química , Survivina/metabolismo
14.
Acta Pharm Sin B ; 10(9): 1619-1633, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33088683

RESUMO

Idiosyncratic drug-induced liver injury (IDILI) is an infrequent but potentially serious disease that develops the main reason for post-marketing safety warnings and withdrawals of drugs. Epimedii Folium (EF), the widely used herbal medicine, has shown to cause idiosyncratic liver injury, but the underlying mechanisms are poorly understood. Increasing evidence has indicated that most cases of IDILI are immune mediated. Here, we report that icariside Ⅱ (ICS Ⅱ), the major active and metabolic constituent of EF, causes idiosyncratic liver injury by promoting NLRP3 inflammasome activation. ICS Ⅱ exacerbates NLRP3 inflammasome activation triggered by adenosine triphosphate (ATP) and nigericin, but not silicon dioxide (SiO2), monosodium urate (MSU) crystal or cytosolic lipopolysaccharide (LPS). Additionally, the activation of NLRC4 and AIM2 inflammasomes is not affected by ICS Ⅱ. Mechanistically, synergistic induction of mitochondrial reactive oxygen species (mtROS) is a crucial contributor to the enhancing effect of ICS Ⅱ on ATP- or nigericin-induced NLRP3 inflammasome activation. Importantly, in vivo data show that a combination of non-hepatotoxic doses of LPS and ICS Ⅱ causes the increase of aminotransferase activity, hepatic inflammation and pyroptosis, which is attenuated by Nlrp3 deficiency or pretreatment with MCC950 (a specific NLRP3 inflammasome inhibitor). In conclusion, these findings demonstrate that ICS Ⅱ causes idiosyncratic liver injury through enhancing NLRP3 inflammasome activation and suggest that ICS Ⅱ may be a risk factor and responsible for EF-induced liver injury.

15.
Regul Toxicol Pharmacol ; 117: 104781, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32896614

RESUMO

Xuezhikang (XZK) is an extract derived from red yeast rice that is commonly used to treat cardiovascular conditions as a traditional Chinese medicine, both within China and globally. Genotoxicity, acute toxicity, and a 26-week toxicity study in rat have been reported in our previous publication. The present study was designed to assess the long-term safety of XZK when administered orally to dogs. Dogs were treated with encapsulated XZK at a maximum dose of 2000 mg/kg followed by 1000 mg/kg and 500 mg/kg (n = 6/sex/group) for this 26-week oral toxicity study. Control animals were given an empty capsule. Treated animals were then monitored through measurements of body weight, body temperature, food intake, ophthalmic and electrocardiogram examinations, general clinical observations, mortality rates, and clinical and anatomic pathological findings. Additionally, blood samples were collected and used to conduct hematological and biochemical analysis. Several abnormalities were found in all groups including: fecal abnormalities (including mucoid, poorly formed, or liquid feces). Moreover, reduced CHOL and TRIG values were seen in all XZK groups (p < 0.05), increased WBC and NEUT levels in 500 mg/kg group (males only, p < 0.05), and elevated AST, ALT, and ALP activities in 2000 mg/kg group (p < 0.05). These changes were resolved in the recovery period. The results indicated that XZK may temporarily impact the liver enzyme levels, but were not considered adverse effects. These findings yielded a NOAEL for XZK in dogs of 2000 mg/kg.


Assuntos
Produtos Biológicos/toxicidade , Medicamentos de Ervas Chinesas/toxicidade , Recuperação de Função Fisiológica/efeitos dos fármacos , Testes de Toxicidade Subcrônica/métodos , Administração Oral , Animais , Produtos Biológicos/sangue , Cães , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/metabolismo , Feminino , Masculino , Recuperação de Função Fisiológica/fisiologia , Fatores de Tempo
16.
Curr Med Sci ; 40(4): 597-601, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32767260

RESUMO

In late December 2019, COVID-19 was firstly recognized in Wuhan, China and spread rapidly to all of the provinces of China. The West Campus of Wuhan Union Hospital, the designated hospital to admit and treat the severe and critically ill COVID-19 cases, has treated a large number of such patients with great success and obtained lots of valuable experiences based on the Chinese guideline (V7.0). To standardize and share the treatment procedures of severe and critically ill cases, Wuhan Union Hospital has established a working group and formulated an operational recommendation, including the monitoring, early warning indicators, and several treatment principles for severe and critically ill cases. The treatment experiences may provide some constructive suggestions for treating the severe and critically ill COVID-19 cases all over the world.


Assuntos
Betacoronavirus , Infecções por Coronavirus/terapia , Pneumonia Viral/terapia , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticoagulantes/uso terapêutico , Antivirais/uso terapêutico , COVID-19 , Teste para COVID-19 , China/epidemiologia , Técnicas de Laboratório Clínico , Terapia Combinada , Comorbidade , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Estado Terminal , Dexametasona/uso terapêutico , Hospitais , Humanos , Imunização Passiva , Medicina Tradicional Chinesa , Pandemias , Pneumonia Viral/epidemiologia , Terapia Respiratória/métodos , SARS-CoV-2 , Tratamento Farmacológico da COVID-19 , Soroterapia para COVID-19
17.
Chemosphere ; 258: 127327, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32559493

RESUMO

Microparticle sorbents (MPSs) containing nano-Fe3O4 core, nano-layered double hydroxides shell modified with different transitional elements (TE-MPSs) are effective for capturing phosphate from wastewater. In present article, different TE-MPSs loaded with Ce, La, Zr and Hf were synthesized and the phosphorous removal performances were compared. The molecular-level mechanism of phosphate adsorption was successfully simulated by pseudo-atom model based on virtual crystal approximation method, which was in line with the spectroscopic data. The results confirmed the inter-sphere complexation reaction between phosphate and TE-MPSs under neutral pH. And the adsorption mechanism probably changed during cycles of adsorption/regeneration. As revealed by elemental composition analysis, ion exchange mechanism probably played an important part in phosphate adsorption in Cycle 1 while the ligand complexation became dominant after regenerated with NaOH in the following cycles. This work indicates that the highly effective, easily separable and repeatedly usable TE-MPSs has the potential for phosphate sequestration and recovery from sewage wastewater.


Assuntos
Nanopartículas de Magnetita , Fosfatos/química , Adsorção , Concentração de Íons de Hidrogênio , Hidróxidos/química , Fósforo , Esgotos , Elementos de Transição , Águas Residuárias/química
18.
Environ Sci Pollut Res Int ; 27(17): 21476-21486, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32274692

RESUMO

Traditional Fenton reagents are less effective for industrial wastewater treatment because they are active in a narrow pH range, precipitate and become inactive, and are difficult to recover. In this study, a heterogeneous Fenton catalyst, γ-Cu-Ce-Al2O3, was prepared by the sol-gel method and evaluated for the treatment of phenol-containing water. The optimal mix of γ-Cu-Ce-Al2O3 includes a Cu content of 5 wt% and a molar ratio between Cu and Ce of 2:1. The catalyst was prepared by continuously stirring the solution for 24 h and heating to 550 °C for 6 h. The Fenton catalyst was tested with hydrogen peroxide for phenol degradation. An initial phenol concentration of 100 mg/L was removed with 95% efficiency. Additionally, the catalyst was demonstrated to be effective for reuse up to five times with an overall removal rate of 72.3%. The test conditions were based on a catalyst dosage of 1.6 g/L, a hydrogen peroxide dosage of 200 mmol/L, a reaction temperature of 40 °C, an initial pH of 7.0 ± 0.05, and a reaction time of 120 min.


Assuntos
Fenol , Poluentes Químicos da Água , Óxido de Alumínio , Catálise , Peróxido de Hidrogênio , Oxirredução , Fenóis
19.
Regul Toxicol Pharmacol ; 114: 104654, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32278069

RESUMO

Xuezhikang (XZK), an extract derived from red yeast rice, is commonly employed as a traditional Chinese medicine for treating coronary heart disease, improving endothelial function, decreasing blood lipids and preventing other cardiovascular events both within China and globally. However, there have not been studies of the toxicity associated with XZK. In this publication we hope to summarize and evaluate an acute study, a 26-week chronic toxicity study, and the genetic toxicity potential of XZK. Firstly, Sprague Dawley (SD) rats were treated with XZK at dose of 10 g/kg to observe the acute toxicity. Then, we sought to assess the toxicity of XZK (0, 500, 1000, and 2000 mg/kg) in SD rats for 26 weeks with a 4-week recovery period. Lastly, we assessed the genotoxicity of XZK utilizing an Ames test, chromosomal aberration assay, and mammalian micronucleus test. The results of the acute study, XZK did not induce toxicity up to the maximum doses of 10 g/kg in rats, so an LD50 could not be determined. In the chronic study, XZK administrated via gavage did not alter weight, food intake, urinalysis parameters, hematological analysis parameters, organ weight, organ to weight ratio, microscopic and macroscopic examination of organs. Also, we found no genotoxicity markers at any dose of XZK tested. The results revealed that the no observed adverse effect level (NOAEL) for XZK, based on the 26-week toxicity study, was 2000 mg/kg.


Assuntos
Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/toxicidade , Extratos Vegetais/administração & dosagem , Extratos Vegetais/toxicidade , Administração Oral , Animais , China , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/química , Feminino , Masculino , Testes de Mutagenicidade , Nível de Efeito Adverso não Observado , Extratos Vegetais/química , Ratos , Ratos Sprague-Dawley , Fatores de Tempo
20.
J Ethnopharmacol ; 248: 112323, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-31639487

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Ginsenoside compound K (CK), a product produced by the intestinal bacteria-mediated breakdown of ginsenoside, exhibits a wide array of pharmacological activities against diverse targets. However, few of preclinical safety evaluation of CK is reported. AIMS OF THE STUDY: The present study therefore sought to assess the toxicity of oral CK in Beagle dogs over a 26-week period. MATERIAL AND METHODS: All dogs received 4, 12, or 36 mg/kg oral CK doses for 26 weeks with regular monitoring, followed by a 4-week recovery period. Animals were monitored through measurements of temperature, weight, food intake, blood chemistry and hematological findings, electrocardiogram (ECG) measurements, urinalysis, gross necropsy and organ weight and tissue histopathology. RESULTS: Animals in the 36 mg/kg group exhibited an apparent reduction in body weight over the study period, in addition to the presence of focal liver necrosis and increased plasma enzyme levels (alanine aminotransferase, ALT; alkaline phosphatase, ALP) consistent with hepatotoxicity, although there was some evidence suggesting this toxicity was reversible. Animals in the 4 and 12 mg/kg groups did not exhibit any apparent toxicity for any measured parameters. CONCLUSION: These results thus indicate that the no observed adverse effect level (NOAEL) in dogs is 12 mg/kg.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/etiologia , Ginsenosídeos/toxicidade , Fígado/efeitos dos fármacos , Administração Oral , Alanina Transaminase/sangue , Fosfatase Alcalina/sangue , Animais , Biomarcadores/sangue , Doença Hepática Induzida por Substâncias e Drogas/sangue , Doença Hepática Induzida por Substâncias e Drogas/patologia , Cães , Relação Dose-Resposta a Droga , Feminino , Ginsenosídeos/administração & dosagem , Fígado/metabolismo , Fígado/patologia , Masculino , Necrose , Nível de Efeito Adverso não Observado , Medição de Risco , Fatores de Tempo , Redução de Peso/efeitos dos fármacos
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