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1.
Drug Dev Res ; 85(1): e22131, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37943623

RESUMEN

Proprotein convertase subtilisin/kexin type 9 (PCSK9) has attracted lots of attention in preventing the clearance of plasma low-density lipoprotein cholesterol (LDL-C). PCSK9 inhibitors are developed to primarily reduce the cardiovascular risk by lowering LDL-C level. Recently, a number of pleiotropic extrahepatic functions of PCSK9 beyond the regulation of cholesterol metabolism, particularly its effects on central nervous system (CNS) diseases have been increasingly identified. Emerging clinical evidence have revealed that PCSK9 may play a significant role in neurocognition, depression, Alzheimer's disease, and stroke. The focus of this review is to elucidate the functions of PCSK9 and highlight the effects of PCSK9 in CNS diseases, with the aim of identifying the potential risks that may arise from low PCSK9 level (variant or inhibitor) in the clinical practice.


Asunto(s)
Enfermedades del Sistema Nervioso Central , Proproteína Convertasa 9 , Humanos , Proproteína Convertasa 9/metabolismo , LDL-Colesterol/metabolismo , Subtilisinas , Enfermedades del Sistema Nervioso Central/tratamiento farmacológico
2.
Drug Dev Res ; 84(2): 326-336, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36567647

RESUMEN

Half of the world's population is Helicobacter pylori carrier. Updated guidelines and consensus have been issued across regions with the main aim of reducing social transmission and increasing H. pylori eradication rate. Although alternative therapies including traditional Chinese medicine and probiotics have also been used to improve H. pylori eradication rate in clinical practice, current mainstream treatment is still dependent on triple and quadruple therapies that includes antibacterial agents (e.g., amoxicillin and furazolidone) and proton pump inhibitor. Researches also assessed the eradication rate of optimized high-dose dual therapy in treating H. pylori infection. With the increase of antibiotic resistance rate, the treatment strategies for H. pylori infection are constantly adjusted and improved. Besides, low medication compliance is another key influencing factor for H. pylori treatment failure. Emerging studies indicate that pharmacists' intervention and new pharmaceutical care methods can enhance patient medication compliance, reduce adverse drug reactions, and improve H. pylori eradication rate. The purpose of this review is to summarize the advances in treating H. pylori infection and highlight the necessity of developing novel strategies to cope with the increasing challenges and to achieve personalized medication. Also, this review attaches great importance to pharmacists in optimizing H. pylori treatment outcomes as a routine part of therapy.


Asunto(s)
Infecciones por Helicobacter , Helicobacter pylori , Humanos , Infecciones por Helicobacter/tratamiento farmacológico , Infecciones por Helicobacter/microbiología , Administración del Tratamiento Farmacológico , Farmacéuticos , Quimioterapia Combinada , Antibacterianos/farmacología , Resultado del Tratamiento
3.
J Phys Chem A ; 125(33): 7289-7296, 2021 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-34383502

RESUMEN

An accurate global potential energy surface (PES) for the HBr2 system has been constructed using the fundamental invariant neural network fitting method based upon 11 698 ab initio energies at the UCCSD(T)/CBS level of theory, with the spin-orbit coupling of the 2P3/2 orbit of the Br atom properly included. The time-dependent wave packet calculations have been performed to study the H + Br2 → HBr + Br reaction on the new PES. The total reaction probabilities for total angular momentum J = 0 for the ground initial state show no threshold due to the submerged barrier height (-0.351 kcal/mol) of the PES. The total integral cross sections (ICS) for reactant Br2 in ro-vibrational states (v0 = 0, j0 = 0, 10, 20, 30; v0 = 1-5, j0 = 0) were calculated for collision energy of up to 0.5 eV. It is found that the initial rotational excitation has a negligible effect on the ICS, and the initial vibrational excitation depresses the reactivity to some extent. The thermal rate constants for the title reaction in the temperature range of 100-1000 K were calculated from the Boltzmann averaging of the v0 = 0-5 rate constants, which overestimated the experimental results to some extent.

4.
Rev Esp Enferm Dig ; 111(10): 738-743, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31373505

RESUMEN

BACKGROUND: proton pump inhibitors (PPI) have been widely used in the clinic but inappropriate prescribing has also increased dramatically. OBJECTIVE: to describe the prescribing patterns and assess the appropriateness of the prescribed PPI use in 45 hospitals in China. MATERIALS AND METHODS: PPI prescriptions for non-hospitalized patients were collected from hospitals in Beijing, Chengdu, Guangzhou and Hangzhou of China over a 40-day period in 2016. These data were analyzed using the prescription number, proportion and economic indicators (defined daily dose system [DDD], defined daily cost [DDC] and drug utilization index [DUI]). The evaluation criteria of PPI use was based on Martindale: The Complete Drug Reference, New Materia Medica and drug instructions. RESULTS: in total, 357,687 prescriptions using oral PPI and 38,216 prescriptions using injectable PPI were assessed. The average age of PPI users was 53 years. The most commonly used oral PPI was rabeprazole, while the most common injectable PPI was pantoprazole. The DDD of oral rabeprazole and DDC of injectable rabeprazole were the highest. Meanwhile, only the DUI values of oral rabeprazole, lansoprazole and ilaprazole were less than 1.0. The clinical diagnosis of some users included well identified risky comorbidities such as kidney disease (2.9%). Furthermore, between 32.6% and 56.8% of the PPI prescriptions were used for inappropriate indications. CONCLUSION: this survey demonstrated that PPI use was accompanied by unapproved indications and excessive dosages. Comprehensive measures are urgently needed to improve PPI use and reduce unnecessary drug costs.


Asunto(s)
Prescripción Inadecuada/estadística & datos numéricos , Inhibidores de la Bomba de Protones/uso terapéutico , 2-Piridinilmetilsulfinilbencimidazoles/administración & dosificación , 2-Piridinilmetilsulfinilbencimidazoles/uso terapéutico , Adolescente , Adulto , China , Comorbilidad , Esomeprazol/administración & dosificación , Esomeprazol/uso terapéutico , Femenino , Encuestas de Atención de la Salud , Hospitales/estadística & datos numéricos , Humanos , Lansoprazol/administración & dosificación , Lansoprazol/uso terapéutico , Masculino , Persona de Mediana Edad , Pantoprazol/administración & dosificación , Pantoprazol/uso terapéutico , Inhibidores de la Bomba de Protones/administración & dosificación , Rabeprazol/administración & dosificación , Rabeprazol/uso terapéutico , Adulto Joven
5.
J Cell Mol Med ; 21(8): 1545-1554, 2017 08.
Artículo en Inglés | MEDLINE | ID: mdl-28244647

RESUMEN

Fibrosis in animal models and human diseases is associated with aberrant activation of the Wnt/ß-catenin pathway. Despite extensive research efforts, effective therapies are still not available. Myofibroblasts are major effectors, responsible for extracellular matrix deposition. Inhibiting the proliferation of the myofibroblast is crucial for treatment of fibrosis. Proliferation of myofibroblasts can have many triggering effects that result in fibrosis. In recent years, the Wnt pathway has been studied as an underlying factor as a primary contributor to fibrotic diseases. These efforts notwithstanding, the specific mechanisms by which Wnt-mediated promotes fibrosis reaction remain obscure. The central role of the transforming growth factor-ß (TGF-ß) and myofibroblast activity in the pathogenesis of fibrosis has become generally accepted. The details of interaction between these two processes are not obvious. The present investigation was conducted to evaluate the level of sustained expression of fibrosis iconic proteins (vimentin, α-SMA and collagen I) and the TGF-ß signalling pathway that include smad2/3 and its phosphorylated form p-smad2/3. Detailed analysis of the possible molecular mechanisms mediated by ß-catenin revealed epithelial-mesenchymal transition and additionally demonstrated transitions of fibroblasts to myofibroblast cell forms, along with increased activity of ß-catenin in regulation of the signalling network, which acts to counteract autocrine TGF-ß/smad2/3 signalling. A major outcome of this study is improved insight into the mechanisms by which epithelial and mesenchymal cells activated by TGFß1-smad2/3 signalling through Wnt/ß-catenin contribute to lung fibrosis.


Asunto(s)
Miofibroblastos/metabolismo , Proteína Smad2/genética , Proteína smad3/genética , Factor de Crecimiento Transformador beta1/genética , Proteínas Wnt/genética , beta Catenina/genética , Células A549 , Actinas/genética , Actinas/metabolismo , Animales , Cadherinas/genética , Cadherinas/metabolismo , Línea Celular , Proliferación Celular , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Transición Epitelial-Mesenquimal , Fibroblastos/metabolismo , Fibroblastos/patología , Fibrosis , Regulación de la Expresión Génica , Humanos , Miofibroblastos/patología , Ratas , Ratas Sprague-Dawley , Transducción de Señal , Proteína Smad2/metabolismo , Proteína smad3/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Vimentina/genética , Vimentina/metabolismo , Proteínas Wnt/metabolismo , beta Catenina/metabolismo
6.
J Pharmacol Exp Ther ; 354(3): 302-9, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26126535

RESUMEN

Epithelial-to-mesenchymal transition (EMT) is a crucial event in the cellular origin of myofibroblasts that secrete extracellular matrix in the progression of pulmonary fibrosis (PF). High-mobility group box 1 (HMGB1) is a novel mediator of EMT. However, whether this process involves the recognized transforming growth factor-ß1 (TGF-ß1)/Smad signaling that also contributes to EMT in PF has not yet been elucidated. Here, we developed a model of PF induced by bleomycin (BLM) in rats and conducted several simulation experiments in A549 (human) and RLE-6TN (rat) alveolar epithelial cell (AEC) lines to unravel the role of TGF-ß1/Smad2/3 signaling in HMGB1-mediated EMT. We found that the levels of serum HMGB1 and lung hydroxyproline were severely elevated after BLM administration. Moreover, the protein expression of HMGB1, TGF-ß1, phosphorylated Smad2/3 (p-Smad2/3), and mesenchymal markers including α-smooth muscle actin, vimentin, and type I collagen were significantly increased with the reduced protein expression of an epithelial marker (E-cadherin) in the rat model by Western blot or immunohistochemical analysis. In addition, the uptake of both exogenous TGF-ß1 and HMGB1 by AECs could induce EMT; meanwhile, HMGB1 dramatically enhanced TGF-ß1 expression and triggered Smad2/3 phosphorylation. In contrast, TGF-ß1 deficiency evidently ameliorated HMGB1-mediated EMT with reduced p-Smad2/3 in A549 cells. It provides new insights that HMGB1 release from injured lungs promotes AEC damage through induction of the EMT process, in which TGF-ß1/Smad2/3 signaling is activated and contributes to PF. These results suggest that HMGB1 may constitute a therapeutic target for developing antifibrotic agents for abnormal lung remodeling.


Asunto(s)
Transición Epitelial-Mesenquimal/fisiología , Proteína HMGB1/metabolismo , Fibrosis Pulmonar/metabolismo , Transducción de Señal/fisiología , Proteína Smad2/metabolismo , Proteína smad3/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Actinas/metabolismo , Animales , Cadherinas/metabolismo , Línea Celular , Línea Celular Tumoral , Colágeno Tipo I/metabolismo , Células Epiteliales/metabolismo , Proteína HMGB1/sangre , Humanos , Hidroxiprolina/metabolismo , Fosforilación/fisiología , Ratas , Ratas Sprague-Dawley , Proteínas Recombinantes , Vimentina/metabolismo
7.
Inflamm Res ; 64(12): 953-61, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26411348

RESUMEN

BACKGROUND: Pulmonary fibrosis (PF) is a fatal inflammatory disease with limited effective strategies. Epithelial-mesenchymal transition (EMT) is a pivotal origin of myofibroblasts that secrete extracellular matrix (ECM) in the development of PF. High mobility group box 1 (HMGB1), one of the mediators of inflammation, has been proved abnormal activation in the pathogenesis of PF. AIM: The present study was aimed to investigate the potential effects of total glycoside of Yupingfeng (YPF-G), the natural compound extracted from Yupingfeng san, on HMGB1 activation and EMT in bleomycin-induced PF, which was a serious disease of respiratory system. METHODS: The Sprague-Dawley (SD) rat model of PF was duplicated by intratracheal instillation of bleomycin (5 mg kg(-1)). After that, YPF-G (5, 10 mg kg(-1)) and prednisone (5 mg kg(-1)) were separately administered intragastrically, and then the rats were killed at days 14 and 28, respectively. Hematoxylin and eosin and Masson's trichrome staining were performed to assess the histopathologic level of lung tissues, western blotting and the common kits were utilized to investigate the hallmarks molecule expression of ECM and EMT, and the level of HMGB1 in lung tissues and serum. RESULTS: We found that both dose of YPF-G markedly reduced bleomycin-induced alveolitis and PF in rats. Besides, the levels of HMGB1, laminin, hyaluronic acid, and hydroxyproline were effectively reduced. Meanwhile, the increased protein expression of HMGB1 and the mesenchymal markers including vimentin and alpha-smooth muscle actin, and the decreased protein expression of epithelial marker E-cadherin were dramatically inhibited after YPF-G treatment. CONCLUSION: Our results demonstrated that YPF-G could ameliorate bleomycin-induced PF by reducing HMGB1 activation and reversing EMT.


Asunto(s)
Bleomicina/antagonistas & inhibidores , Bleomicina/toxicidad , Medicamentos Herbarios Chinos/uso terapéutico , Proteína HMGB1/efectos de los fármacos , Fibrosis Pulmonar/inducido químicamente , Fibrosis Pulmonar/prevención & control , Animales , Antiinflamatorios/farmacología , Relación Dosis-Respuesta a Droga , Transición Epitelial-Mesenquimal/efectos de los fármacos , Matriz Extracelular/efectos de los fármacos , Glicósidos , Hidroxiprolina/metabolismo , Extractos Vegetales/farmacología , Prednisona/farmacología , Ratas , Ratas Sprague-Dawley
8.
J Cell Mol Med ; 18(12): 2331-9, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25284457

RESUMEN

High-mobility group box 1 (HMGB1) is originally identified as a DNA-binding protein that functions as a structural co-factor critical for proper transcriptional regulation in somatic cells. Recent studies indicate that HMGB1 can be passively released from necrotic cells or actively secreted into the extracellular milieu under appropriate signal stimulation. Extracellular HMGB1 is a multifunctional cytokine that contributes to the process of infection, injury, inflammation, apoptosis, and immune responses by binding to specific cell-surface receptors. Recently, emerging studies indicate that HMGB1 is closely involved in fibrotic disorders including cystic fibrosis, liver fibrosis and pulmonary fibrosis, while HMGB1 signal inhibitions protect against the experimental models of fibrotic diseases. From a clinical perspective, HMGB1 represents a current challenge that can be exploited orchestrate reparative responses. This review focuses on the crucial role of HMGB1 in the pathogenesis of fibrotic diseases and inhibition of which may represent a promising clinical approach for treating tissue fibrosis.


Asunto(s)
Fibrosis Quística/fisiopatología , Proteína HMGB1/fisiología , Cirrosis Hepática/fisiopatología , Fibrosis Pulmonar/fisiopatología , Animales , Anticuerpos/inmunología , Anticuerpos/uso terapéutico , Fibrosis Quística/tratamiento farmacológico , Fibrosis Quística/metabolismo , Proteína HMGB1/antagonistas & inhibidores , Proteína HMGB1/inmunología , Proteína HMGB1/metabolismo , Humanos , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/metabolismo , Modelos Biológicos , Terapia Molecular Dirigida , Fibrosis Pulmonar/tratamiento farmacológico , Fibrosis Pulmonar/metabolismo , Transducción de Señal/efectos de los fármacos
9.
J Pharmacol Exp Ther ; 351(2): 336-43, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25194021

RESUMEN

Fibrotic diseases occur in a variety of organs and lead to continuous organ injury, function decline, and even failure. Currently effective treatment options are limited. Galectin-3 (Gal-3) is a pleiotropic lectin that plays an important role in cell proliferation, adhesion, differentiation, angiogenesis, and apoptosis. Accumulating evidence indicates that Gal-3 activates a variety of profibrotic factors, promotes fibroblast proliferation and transformation, and mediates collagen production. Recent studies have defined key roles for Gal-3 in fibrogenesis in diverse organ systems, including liver, kidney, lung, and myocardial. To help set the stage for future research, we review recent advances about the role played by Gal-3 in fibrotic diseases. Herein we discuss the potential profibrotic role of Gal-3, inhibition of which may represent a promising therapeutic strategy against tissue fibrosis.


Asunto(s)
Fibrosis/metabolismo , Galectina 3/metabolismo , Animales , Humanos
10.
Int J Gen Med ; 17: 2055-2063, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38751493

RESUMEN

Surveillance of drug safety is an important aspect in the routine medical care. Adverse events caused by real-world drug utilization has become one of the leading causes of death and an urgent issue in the field of toxicology. Cardiovascular disease is now the leading cause of fatal diseases in most countries, especially in the elderly population who often suffer from multiple diseases and need long-term multidrug therapy. Among which, statins have been widely used to lower bad cholesterol and regress coronary plaque mainly in patients with hyperlipidemia and atherosclerotic cardiovascular diseases (ASCVD). Although the real-world benefits of statins are significant, different degrees and types of adverse drug reactions (ADR) such as liver dysfunction and muscle injury, have a great impact on the original treatment regimens as well as the quality of life. This review describes the epidemiology, mechanisms, early identification and post-intervention of statin-associated liver dysfunction and muscle injury based on the updated clinical evidence. It provides systematic and comprehensive guidance and necessary supplement for the clinical safety of statin use in cardiovascular diseases.

11.
Nat Cancer ; 5(1): 131-146, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38168934

RESUMEN

Availability of the essential amino acid methionine affects cellular metabolism and growth, and dietary methionine restriction has been implicated as a cancer therapeutic strategy. Nevertheless, how liver cancer cells respond to methionine deprivation and underlying mechanisms remain unclear. Here we find that human liver cancer cells undergo irreversible cell cycle arrest upon methionine deprivation in vitro. Blocking methionine adenosyl transferase 2A (MAT2A)-dependent methionine catabolism induces cell cycle arrest and DNA damage in liver cancer cells, resulting in cellular senescence. A pharmacological screen further identified GSK3 inhibitors as senolytics that selectively kill MAT2A-inhibited senescent liver cancer cells. Importantly, combined treatment with MAT2A and GSK3 inhibitors therapeutically blunts liver tumor growth in vitro and in vivo across multiple models. Together, methionine catabolism is essential for liver tumor growth, and its inhibition can be exploited as an improved pro-senescence strategy for combination with senolytic agents to treat liver cancer.


Asunto(s)
Glucógeno Sintasa Quinasa 3 , Neoplasias Hepáticas , Humanos , S-Adenosilmetionina/metabolismo , S-Adenosilmetionina/farmacología , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/genética , Metionina/farmacología , Metionina Adenosiltransferasa/metabolismo
12.
Front Cardiovasc Med ; 10: 1133662, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38274318

RESUMEN

For patients with cardiovascular disease, using the antidepressant escitalopram may lead to unexpected adverse events. Here, a rare repeated sinus bradycardia event due to escitalopram is first reported. In an 82-year-old female patient with cardiac dysfunction using digoxin, tachycardia (average heart rate of 93 beats/min) was demonstrated by electrocardiogram (ECG). She began to take escitalopram and lorazepam due to depression, but sinus bradycardia (93.7% heart rate was <60 beats/min) and sinus arrest were first detected after 3 months. Its proportion decreased to 0.1% after discontinuation of digoxin and escitalopram for 1 day, and the rhythm returned to normal 2 weeks later. After 2 months, escitalopram was prescribed again in combination with quetiapine; then, 17.1% heart rate was <60 beats/min. After escitalopram and quetiapine withdrawal, the ECG showed the heart rhythm had normalized again. No other drug changes were made during these periods. Escitalopram was deemed to be a highly possible cause of sinus bradycardia according to its Naranjo's Algorithm score. Furthermore, literature on escitalopram-mediated cardiovascular adverse events was reviewed and analyzed. Empirically, escitalopram should be discontinued immediately if iatrogenic causes cannot be ruled out. Furthermore, ECG monitoring in escitalopram-related cardiovascular adverse events is highlighted, especially in patients receiving certain drug classes simultaneously (i.e., sinoatrial node inhibitors, antipsychotics).

13.
Risk Manag Healthc Policy ; 16: 287-299, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36875172

RESUMEN

Background: Pediatric hypertension become an early marker of cardiovascular diseases, but their antihypertensive drug use patterns are rarely known. Purpose: To investigate the epidemiological characteristics of pediatric hypertension and the use of antihypertensive drugs in the real world in China. Methods: In this study, the demographic, diagnosis, and medication prescription data including the antihypertensive drug types and comorbidities, were analyzed. The antihypertensive drugs use were evaluated according to the Chinese guidelines for hypertension. Results: 1301 prescriptions (number of visits) containing 1880 antihypertensive medical orders were collected. The average number of antihypertensive drugs per prescription was 1.45 (±0.75). The patients aged 16 to 18 (70.18%) accounted for the highest proportion. Kidney diseases (33.28%) were the most common comorbidities. Calcium channel blocker (CCB), angiotensin II receptor blocker (ARB), and ß receptor blocker (BB) were the most used antihypertensive drugs. The most frequent monotherapy was CCB, while that of two and three drugs combination were ARB+CCB and ARB+BB+CCB, respectively. Metoprolol (11.44%), nifedipine (10.64%), amlodipine (10.59%), valsartan (6.12%) were the most commonly used antihypertensive drugs. The utilization rate of fixed compound preparations was 7.34%. However, the percentage of recommended antihypertensive drugs was just 14.20%, while the recommended drug combination was 84.93% according to the guidelines. Conclusion: For the first time ever we reported the antihypertensive prescription analysis in children in a large area of China. Our data provided new insights into the epidemiological characteristics and drug use in hypertensive children. We found that the guidelines for medication management in hypertensive children were not routinely followed. The wide use of antihypertensive drugs in children and those with weak clinical evidence raised concerns regarding its rational use. The findings could lead to more effective management of hypertension in children.

14.
Oxid Med Cell Longev ; 2022: 5044356, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35795853

RESUMEN

Air pollution is a serious threat to human health. Inhaled fine particulate matter (PM2.5) can cause inflammation and oxidative stress in the airway; however, the mechanisms responsible for this effect have yet to be elucidated and there are no specific drugs that can prevent and treat this condition. In the present study, we investigated the effects and mechanisms underlying the inhalation of salvianolic acid B (SalB) on PM2.5-induced airway inflammation and oxidative stress. We used a PM2.5-induced mouse model of airway inflammation and oxidative stress, along with a human epithelial cell model, to study the action and mechanisms of SalB by histopathology, real-time PCR, enzyme-linked immunosorbent assays, flow cytometry, and western blotting. SalB treatment markedly inhibited the PM2.5-induced increase in the number of neutrophils and macrophages in bronchoalveolar lavage fluid, improved the infiltration of inflammatory cells in lung tissue, and reduced injury in the alveolar septum. Furthermore, SalB reduced the mRNA and protein levels of interleukin- (IL-) 1ß, tumor necrosis factor- (TNF-) α, keratinocyte (KC), and transforming growth factor- (TGF-) ß1 in lung tissues and the protein levels of IL-1ß, TNF-α, IL-8, IL-6, and TGF-ß1 in human epithelial cells. SalB treatment also significantly prevented the reduction of levels of superoxide dismutase, catalase, glutathione, and glutathione peroxidase in lung tissue and reduced the levels of reactive oxygen species in human epithelial cells induced by PM2.5. Furthermore, SalB and the myeloid differentiation primary response 88 (MyD88) inhibitor ST2825 inhibited the expression levels of toll-like receptor 4 (TLR4), MyD88, tumor necrosis factor receptor associated factor 6 (TRAF-6), and NOD-like receptor protein 3 (NLRP3), as well as the phosphorylation of downstream Erk1/2 and P38 in lung tissue and epithelial cells. SalB protects against PM2.5-induced airway inflammation and oxidative stress in a manner that is associated with the inhibition of the TLR4/MyD88/TRAF-6/NLRP3 pathway and downstream signals ERK1/2 and P38.


Asunto(s)
Benzofuranos , Factor 88 de Diferenciación Mieloide , Estrés Oxidativo , Material Particulado , Animales , Benzofuranos/farmacología , Inflamación/inducido químicamente , Inflamación/patología , Inflamación/prevención & control , Ratones , Factor 88 de Diferenciación Mieloide/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Proteínas NLR/metabolismo , Estrés Oxidativo/efectos de los fármacos , Material Particulado/antagonistas & inhibidores , Material Particulado/toxicidad , Transducción de Señal/efectos de los fármacos , Receptor Toll-Like 4/metabolismo
15.
Toxicology ; 469: 153114, 2022 03 15.
Artículo en Inglés | MEDLINE | ID: mdl-35114310

RESUMEN

Silicosis is the most serious occupational pulmonary fibrosis caused by excessive inhalation of silica particles, whereas viable therapeutic choices are constrained. Epigallocatechin gallate (EGCG) presents massive health benefits, but unfortunately with stability absence. Here, encapsulation of EGCG in poly(n-butylcyanoacrylate) nanoparticles (EGCG/PBCA-NPs) were fabricated by self-polymerization for gastrointestinal delivery in silicosis fibrosis treatment. The obtained nano-enabled delivery of EGCG was produced using a medical adhesive approved by FDA as carrier, and presented spherical particles with approximate diameter of 160 nm, a narrow PDI value of 0.2, Zeta potential value of 30 mV as well as a high EGCG incorporation (90 %) and loading efficiency (20 %). In evaluating the protect effects of nano-formulations, EGCG/PBCA-NPs shown excellent stability in gastric fluid with pH-triggered release in intestine and strong EGCG gastrointestinal retention against degradation. After daily gastrointestinal administration, EGCG/PBCA-NPs exhibited the superior anti-fibrosis efficacy in silicosis model rats induced by silica, involving lung index decline, hydroxyproline content decrease, histological improvement, collagen accumulation reduction and α-SMA down-regulation in comparison with naked EGCG. These results strongly demonstrated that PBCA-based NPs may be a promising nano-enabled delivery carrier for enhancing the gastrointestinal stability and anti-fibrotic effects of EGCG.


Asunto(s)
Catequina , Nanopartículas , Fibrosis Pulmonar , Silicosis , Animales , Catequina/análogos & derivados , Catequina/farmacología , Catequina/uso terapéutico , Fibrosis Pulmonar/inducido químicamente , Fibrosis Pulmonar/tratamiento farmacológico , Fibrosis Pulmonar/prevención & control , Ratas , Dióxido de Silicio/toxicidad , Silicosis/tratamiento farmacológico
16.
Guang Pu Xue Yu Guang Pu Fen Xi ; 31(10): 2651-4, 2011 Oct.
Artículo en Zh | MEDLINE | ID: mdl-22250527

RESUMEN

A radio-frequency discharge setup was constructed by two shell-shaped copper electrodes and a 30 cm long pyrex glass tube (i. d. = 1.65 cm) to examine the gas temperature of oxygen plasma in electric discharge oxygen iodine laser. The discharge was supplied by a 500 watt, 13.56 MHz radio-frequency power. The gas pressure in the discharge cavity was 1 330 Pa. The temperature of oxygen discharge plasma was measured by using the P branch of O2 (b, v = 0) rotational emission spectrum. Two methods were used to deduce the oxygen gas temperature. They are Boltzman plotting method and computer simulating spectrum method, respectively. Gauss fitting method was used to distinguish spectrum peaks for lower resolution spectrum. The spectrum peak area was used to characterize the optical emission intensity. The gas temperature of oxygen discharge plasma was obtained by Boltzmann plotting method. Alternatively, the optical emission spectrum was simulated by computer modeling with spectrometer slit function which was obtained by He-Ne laser. Consequently, the gas temperature of oxygen plasma was obtained by comparing the computer simulating spectrum and the experimentally observed spectrum according to the least square fitting rule. The measurement results with the two methods agree well. It was concluded that the simple optical technique can be used conveniently in the temperature diagnostics of oxygen radio-frequency discharge plasma.

17.
Chin Med ; 16(1): 130, 2021 Dec 03.
Artículo en Inglés | MEDLINE | ID: mdl-34861881

RESUMEN

The Coronavirus disease 2019 (COVID-19) pandemic is still spread and has made a severe public health threat around the world. To improve disease progression, emerging Chinese herbal compounds were used in clinical practice and some agents have proven beneficial in treating COVID-19. Here, the relevant literature from basic researches to clinical application were identified and comprehensively assessed. A variety of Chinese herbal compounds have been reported to be effective in improving symptoms and outcomes in patients with COVID-19, particularly together with routine treatment strategy. The pharmacological activities were mainly attributed to the relief of clinical symptoms, inhibition of cytokine storm, and improvement of organ function. Besides, the development of novel antiviral drugs from medicinal herbs were further discussed. The updated laboratory and clinical studies provided the evidence of Chinese herbal compounds such as Lianhua Qingwen prescription, Shufeng Jiedu prescription, and Qingfei Paidu Tang for the relief of COVID-19. However, both of the randomized controlled trials and real world researches need to be done for supporting the evidence including the efficacy and safety in fighting COVID-19.

18.
Int Clin Psychopharmacol ; 36(5): 274-278, 2021 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-34102650

RESUMEN

Parkinson's disease (PD) is a neurological disorder involving both motor and nonmotor symptoms. Multimorbidity acts synergistically to heighten the risk of adverse outcomes for patients with PD. Its complications have a major impact on the clinical management of PD. The present retrospective and multicenter study was first performed to describe the epidemiological characteristics of PD patients and assess the incidence of complications. The outpatient prescriptions for PD therapy were collected from hospitals in Beijing, Chengdu, Guangzhou, Hangzhou, Shanghai, Tianjin and Zhengzhou of China over a 40-day period per year, from the first half of 2016 to that of 2019. The survey covered the characteristics and representative complications of the study population. A total of 103 674 outpatient prescriptions for PD treatment from different graded hospitals of China were collected for final data analysis. It showed that 78.15% of PD patients were prescribed in the neurology department. 95.05% of the outpatient prescriptions were from general hospitals. We found that the overall PD prevalence was 0.47%, among which 52.96% of them were men. In addition, 82.10% of PD suffers were older than 60 years and 83.70% of them had complications. The top five highest frequencies of nonmotor complications in PD patients were sleep disorders, Alzheimer's disease, depression, lower urinary tract symptoms and constipation, with the proportions of 6.79, 3.87, 3.72, 3.32 and 2.40%, respectively. Meanwhile, the proportions of sleep disorders, Alzheimer's disease, and constipation were gradually increasing from 2016 to 2019. The characteristics of PD patients and the incidence of its complications were evaluated in the present prescription survey. These updated data provide evidence for further implementation of PD management.


Asunto(s)
Multimorbilidad , Enfermedad de Parkinson , China/epidemiología , Ciudades/epidemiología , Humanos , Multimorbilidad/tendencias , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/epidemiología , Estudios Retrospectivos
19.
Drug Des Devel Ther ; 15: 111-124, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33469264

RESUMEN

Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death across the globe. Its repeated exacerbation will seriously worsen the quality of life, aggravate the patients' symptoms, and bring a heavy burden on the patients and the society. Understanding the current status of drug therapy and the role of pharmaceutical care is essential for the management of COPD. In addition to the drugs already on the market, recent clinical trials also show that emerging novel drugs for treating COPD are being developed to prevent the symptoms, reduce the frequency of acute exacerbation, and improve the quality of life. Recent progress in new drug research should lead to novel treatment options for COPD patients in future clinical practice. The pharmaceutical care has shown significantly favourable impacts on addressing drug-related problems, supporting its vital role in the management of COPD, especially when there are a wide range of therapeutic agents. This review not only provides an overview of current treatment strategies but also further underlines the importance of new drug development and pharmaceutical care for patients with COPD.


Asunto(s)
Broncodilatadores/uso terapéutico , Administración del Tratamiento Farmacológico , Farmacéuticos , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Humanos
20.
Integr Med Res ; 10(4): 100778, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34608432

RESUMEN

BACKGROUND: The outbreak of Coronavirus disease 2019 (COVID-19) has caused more than 180 million infections and 3.9 million deaths. To date, emerging clinical evidence has shown the synergetic benefits of Chinese herbal injections in treating this contagious respiratory disease. This review aims to summarize and analyze the efficacy and safety of Chinese herbal injections in the therapy of COVID-19. METHODS: The literature from 3 electronic databases, PubMed, CNKI, and Web of Science, were searched using the search terms "COVID-19", "SARS-CoV-2", "traditional Chinese medicine", "herb", "herbal", and "injection". Then the identified articles were comprehensively evaluated. RESULTS: Limited data demonstrated that Chinese herbal injections could significantly improve the clinical outcomes of COVID-19 patients, especially in combination with conventional treatment strategies. The benefits of which were mainly associated with the relief of symptoms, prevention of secondary infection, regulation of inflammation and immune function. There was also evidence showing the inhibitory effects on SARS-CoV-2 replication in vitro. Nevertheless, available real-world data suggested the increased risk of adverse event. Furthermore, the defects of existing researches and the insights for discovering novel antiviral drugs were prospectively discussed. CONCLUSION: Evidence-based advances revealed that Chinese herbal injections such as XueBiJing injection and ShenMai injection, exerted potent effects against COVID-19. Further laboratory researches and clinical evaluation are needed to gather scientific evidence on the efficacy and safety.

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