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Atherosclerosis is a common form of cardiovascular disease, which is one of the most prevalent causes of death worldwide, particularly among older individuals. Surgery is the mainstay of treatment for severe stenotic lesions, though the rate of restenosis remains relatively high. Current medication therapy for atherosclerosis has limited efficacy in reversing the formation of atherosclerotic plaques. The search for new drug treatment options is imminent. Some potent medications have shown surprising therapeutic benefits in inhibiting inflammation and endothelial proliferation in plaques. Unfortunately, their use is restricted due to notable dose-dependent systemic side effects or degradation. Nevertheless, with advances in nanotechnology, an increasing number of nano-related medical applications are emerging, such as nano-drug delivery, nano-imaging, nanorobots, and so forth, which allow for restrictions on the use of novel atherosclerotic drugs to be lifted. This paper reviews new perspectives on the targeted delivery of nanoparticles to blood vessels for the treatment of atherosclerosis in both systemic and local drug delivery. In systemic drug delivery, nanoparticles inhibit drug degradation and reduce systemic toxicity through passive and active pathways. To further enhance the precise release of drugs, the localized delivery of nanoparticles can also be accomplished through blood vessel wall injection or using endovascular interventional devices coated with nanoparticles. Overall, nanotechnology holds boundless potential for the diagnosis and treatment of atherosclerotic diseases in the future.
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INTRODUCTION: Corilagin possesses a diverse range of pharmacologic bioactivities. However, the specific protective effects and mechanisms of action of corilagin in the context of atherosclerosis remain unclear. In this study, we investigated the impact of corilagin on the toll-like receptor (TLR)4 signaling pathway in a mouse vascular smooth muscle cell line (MOVAS) stimulated by oxidized low-density lipoprotein (ox-LDL). Additionally, we examined the effects of corilagin in Sprague-Dawley rats experiencing atherosclerosis. METHODS: The cytotoxicity of corilagin was assessed using the CCK8 assay. MOVAS cells, pre-incubated with ox-LDL, underwent treatment with varying concentrations of corilagin. TLR4 expression was modulated by either downregulation through small interfering (si)RNA or upregulation via lentivirus transfection. Molecular expression within the TLR4 signaling pathway was analyzed using real-time polymerase chain reaction (PCR) and Western blotting. The proliferation capacity of MOVAS cells was determined through cell counting. In a rat model, atherosclerosis was induced in femoral arteries using an improved guidewire injury method, and TLR4 expression in plaque areas was assessed using immunofluorescence. Pathological changes were examined through hematoxylin and eosin staining, as well as Oil-Red-O staining. RESULTS: Corilagin demonstrated inhibitory effects on the TLR4 signaling pathway in MOVAS cells pre-stimulated with ox-LDL, consequently impeding the proliferative impact of ox-LDL. The modulation of TLR4 expression, either through downregulation or upregulation, similarly influenced the expression of downstream molecules. In an in vivo context, corilagin exhibited the ability to suppress TLR4 and MyD88 expression in the plaque lesion areas of rat femoral arteries, thereby alleviating the formation of atherosclerotic plaques. CONCLUSION: Corilagin can inhibit the TLR4 signaling pathway in VSMCs, possibly by downregulating TLR4 expression and, consequently, relieving atherosclerosis.
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Aterosclerosis , Glucósidos , Taninos Hidrolizables , Lipoproteínas LDL , Músculo Liso Vascular , Ratas Sprague-Dawley , Transducción de Señal , Receptor Toll-Like 4 , Animales , Receptor Toll-Like 4/metabolismo , Taninos Hidrolizables/farmacología , Transducción de Señal/efectos de los fármacos , Aterosclerosis/tratamiento farmacológico , Aterosclerosis/metabolismo , Aterosclerosis/patología , Músculo Liso Vascular/efectos de los fármacos , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patología , Lipoproteínas LDL/metabolismo , Masculino , Glucósidos/farmacología , Glucósidos/uso terapéutico , Ratones , Línea Celular , Ratas , Proliferación Celular/efectos de los fármacos , Miocitos del Músculo Liso/efectos de los fármacos , Miocitos del Músculo Liso/metabolismo , Miocitos del Músculo Liso/patología , Modelos Animales de Enfermedad , Factor 88 de Diferenciación Mieloide/metabolismoRESUMEN
Photosensors with versatile functionalities have emerged as a cornerstone for breakthroughs in the future optoelectronic systems across a wide range of applications. In particular, emerging photoelectrochemical (PEC)-type devices have recently attracted extensive interest in liquid-based biosensing applications due to their natural electrolyte-assisted operating characteristics. Herein, a PEC-type photosensor was carefully designed and constructed by employing gallium nitride (GaN) p-n homojunction semiconductor nanowires on silicon, with the p-GaN segment strategically doped and then decorated with cobalt-nickel oxide (CoNiOx). Essentially, the p-n homojunction configuration with facile p-doping engineering improves carrier separation efficiency and facilitates carrier transfer to the nanowire surface, while CoNiOx decoration further boosts PEC reaction activity and carrier dynamics at the nanowire/electrolyte interface. Consequently, the constructed photosensor achieves a high responsivity of 247.8 mA W-1 while simultaneously exhibiting excellent operating stability. Strikingly, based on the remarkable stability and high responsivity of the device, a glucose sensing system was established with a demonstration of glucose level determination in real human serum. This work offers a feasible and universal approach in the pursuit of high-performance bio-related sensing applications via a rational design of PEC devices in the form of nanostructured architecture with strategic doping engineering.
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Schistosomiasis is a parasitic disease that endangers human health and social development. The granulomatous reaction of Schistosoma eggs in the liver is the main cause of hepatosplenomegaly and fibrotic lesions. Anti liver fibrosis therapy is crucial for patients with chronic schistosomiasis. Although Praziquantel is the only clinical drug used, it is limited in insecticide treatment and has a long-term large-scale use, which is forcing the search for cost-effective alternatives. Previous research has demonstrated that plant metabolites and extracts have effective therapeutic effects on liver fibrosis associated with schistosomiasis. This paper summarizes the mechanisms of action of metabolites and some plant extracts in alleviating schistosomiasis-associated liver fibrosis. The analysis was conducted using databases such as PubMed, Google Scholar, and China National Knowledge Infrastructure (CNKI) databases. Some plant metabolites and extracts ameliorate liver fibrosis by targeting multiple signaling pathways, including reducing inflammatory infiltration, oxidative stress, inhibiting alternate macrophage activation, suppressing hepatic stellate cell activation, and reducing worm egg load. Natural products improve liver fibrosis associated with schistosomiasis, but further research is needed to elucidate the effectiveness of natural products in treating liver fibrosis caused by schistosomiasis, as there is no reported data from clinical trials in the literature.
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Introduction: Atherosclerosis, a leading cause of global cardiovascular mortality, is characterized by chronic inflammation. Central to this process is the NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome, which significantly influences atherosclerotic progression. Recent research has identified that the olfactory receptor 2 (Olfr2) in vascular macrophages is instrumental in driving atherosclerosis through NLRP3- dependent IL-1 production. Methods: To investigate the effects of Corilagin, noted for its anti-inflammatory attributes, on atherosclerotic development and the Olfr2 signaling pathway, our study employed an atherosclerosis model in ApoE-/- mice, fed a high-fat, high-cholesterol diet, alongside cellular models in Ana-1 cells and mouse bone marrow-derived macrophages, stimulated with lipopolysaccharides and oxidized low-density lipoprotein. Results: The vivo and vitro experiments indicated that Corilagin could effectively reduce serum lipid levels, alleviate aortic pathological changes, and decrease intimal lipid deposition. Additionally, as results showed, Corilagin was able to cut down expressions of molecules associated with the Olfr2 signaling pathway. Discussion: Our findings indicated that Corilagin effectively inhibited NLRP3 inflammasome activation, consequently diminishing inflammation, macrophage polarization, and pyroptosis in the mouse aorta and cellular models via the Olfr2 pathway. This suggests a novel therapeutic mechanism of Corilagin in the treatment of atherosclerosis.
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Aterosclerosis , Glucósidos , Taninos Hidrolizables , Inflamasomas , Macrófagos , Proteína con Dominio Pirina 3 de la Familia NLR , Transducción de Señal , Animales , Taninos Hidrolizables/farmacología , Taninos Hidrolizables/uso terapéutico , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Aterosclerosis/tratamiento farmacológico , Aterosclerosis/metabolismo , Ratones , Transducción de Señal/efectos de los fármacos , Inflamasomas/metabolismo , Glucósidos/farmacología , Glucósidos/uso terapéutico , Macrófagos/metabolismo , Macrófagos/inmunología , Macrófagos/efectos de los fármacos , Masculino , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , Ratones Noqueados para ApoERESUMEN
Infectious diseases are the common enemies of mankind. In the course of historical development, they persistently threaten human health and safety. Even today, despite the developments in medical science, we cannot escape the fear and suffering caused by infectious diseases. Whether in ancient or modern times, the source of infection, route of transmission, and a susceptible population are the three key conditions for the prevalence and spread of infectious diseases. All factors closely related to these three conditions can affect the prevalence of infectious diseases. China is one of the cradles of world civilization. The ancient people accumulated a great deal of experience and lessons in the long struggle against infectious diseases. In the face of the current threat posed by widespread infectious disease, it is imperative to review and summarize ancient Chinese ideas and health policies on epidemic prevention and control to inspire contemporary efforts in the prevention and control of infectious disease. The combination of prevention-oriented epidemic prevention ideology and traditional medicine provides valuable insights, especially for impoverished and medically underserved regions.
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Enfermedades Transmisibles , Epidemias , Medicina , Humanos , China/epidemiología , Enfermedades Transmisibles/epidemiologíaRESUMEN
BACKGROUND: Obstructive shock is extremely rare in clinical practice and is caused by acute blood flow obstruction in the central vessels of either the systemic or pulmonary circulation. Utilizing inferior vena cava filters (IVCFs) to prevent pulmonary embolism (PE) is associated with some potential complications, such as inferior vena cava thrombosis (IVCT). Shock as a direct result of IVCT is rare. We present a case of obstructive shock secondary to extensive IVCT caused by inadequate anticoagulant therapy after the placement of an IVCF. CASE PRESENTATION: A 63-year-old male patient with a traffic accident injury presented orthopaedic trauma and lower limb deep vein thrombosis (DVT). He experienced sudden and severe abdominal pain with hypotension, tachycardia, tachypnea, oliguria and peripheral oedema 5 days after IVCF placement and 3 days after cessation of anticoagulant therapy. Considering that empirical anti-shock treatment lasted for a while and the curative effect was poor, we finally recognized the affected vessels and focused on the reason for obstructive shock through imaging findings-inferior vena cava thrombosis and occlusion. The shock state immediately resolved after thrombus aspiration. The same type of shock occurred again 6 days later during transfer from the ICU to general wards and the same treatment was administered. The patient recovered smoothly in the later stage, and the postoperative follow-up at 1, 3, and 12 months showed good results. CONCLUSION: This case alerts clinicians that it is crucial to ensure adequate anticoagulation therapy after IVCF placement, and when a patient presents with symptoms such as hypotension, tachycardia, and lower limb and scrotal oedema postoperatively, immediate consideration should be given to the possibility of obstructive shock, and prompt intervention should be based on the underlying cause.
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INTRODUCTION: This article aims to evaluate the prognostic value of ferritin in patients with severe fever with thrombocytopenia syndrome (SFTS). METHODS: Patients with SFTS diagnosed at the Infection Department of Wuhan Union Medical College Hospital from July 2018 to November 2021 were included. The best cutoff value was determined by receiver-operating characteristic (ROC) curve. The survival curve was analyzed by Kaplan-Meier method and compared among different serum ferritin subgroups by log-rank test. Cox regression model was used to evaluate the effect of prognosis on overall survival (OS). RESULTS: A total of 229 patients with febrile thrombocytopenia syndrome were enrolled. There were 42 fatal cases, with a fatality rate of 18.3%. The best critical value of serum ferritin was 16.775 mg/l. With increasing serum ferritin level, the cumulative mortality increased significantly (log-rank, P < 0.001). Cox univariate regression analysis and adjusted confounding factors such as age, viral load, liver and kidney function and blood coagulation function showed that, compared with the low ferritin group, the high ferritin group demonstrated poorer OS. CONCLUSIONS: The serum ferritin level before treatment can be considered a valuable index for predicting the prognosis of patients with SFTS.
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Corilagin is a naturally occurring water-soluble retrogallic acid tannin, which can be extracted from many kinds of plants. Known at present, it is the main effective ingredient of Phyllanthus urinaria L., Geranium wilfordii Maxim., Phyllanthus matsumurae Hayata, and Trifolium repens L. It also exists in Phyllanthus emblica L., Dimocarpus longan Lour., Canarium album (Lour.) Raeusch., and Terminalia chebula Retz. It can participate in a variety of signaling pathways in vivo and has multiple biological activities, including antitumor, anti-microbial, anti-oxidation, anti-inflammation, hepatoprotective, anti-allergy, anti-proliferation and so on. Given the limited efficacy of first-line treatments for many diseases such as oncology, chronic liver disease, and rheumatic immune system diseases, and the potential for adverse effects to outweigh the therapeutic effects, attention is being focused on alternative treatments, and natural plant extracts are a natural target for alternative treatments, as natural substances tend to have low toxicity to normal tissues. Some proprietary Chinese medicines containing corilagin have been used in clinical applications, being clinically applied to treat chronic liver disease, viral hepatitis B, rheumatoid arthritis and other diseases. This paper reviews the extraction, determination, distribution and harvesting, pharmacokinetics, biological activity, safety assessment of corilagin and its application in clinical practice.
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Taninos Hidrolizables , Phyllanthus , Taninos Hidrolizables/farmacología , Taninos Hidrolizables/uso terapéutico , Glucósidos/uso terapéutico , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéuticoRESUMEN
Vascular smooth muscle cells (VSMCs) are an important source of foam cells in atherosclerosis. The mechanism for VSMC-derived foam cell formation is, however, poorly understood. Here, we demonstrate that the P2RY12/P2Y12 receptor is important in regulating macroautophagy/autophagy and VSMC-derived foam cell formation in advanced atherosclerosis. Inhibition of the P2RY12 receptor ameliorated lipid accumulation and VSMC-derived foam cell formation in high-fat diet-fed apoe-/- mice (atherosclerosis model) independent of LDL-c levels. Activation of the P2RY12 receptor blocked cholesterol efflux via PI3K-AKT, while genetic knockdown or pharmacological inhibition of the P2RY12 receptor inhibited this effect in VSMCs. Phosphoproteomic analysis showed that the P2RY12 receptor regulated the autophagy pathway in VSMCs. Additionally, activation of the P2RY12 receptor inhibited MAP1LC3/LC3 maturation, SQSTM1 degradation, and autophagosome formation in VSMCs. Genetic knockdown of the essential autophagy gene Atg5 significantly attenuated P2RY12 receptor inhibitor-induced cholesterol efflux in VSMCs. Furthermore, activation of the P2RY12 receptor led to the activation of MTOR through PI3K-AKT in VSMCs, whereas blocking MTOR activity (rapamycin) or reducing MTOR expression reversed the inhibition of cholesterol efflux mediated by the P2RY12 receptor in VSMCs. In vivo, inhibition of the P2RY12 receptor promoted autophagy of VSMCs through PI3K-AKT-MTOR in advanced atherosclerosis in apoe-/- mice, which could be impeded by an autophagy inhibitor (chloroquine). Therefore, we conclude that activation of the P2RY12 receptor decreases cholesterol efflux and promotes VSMC-derived foam cell formation by blocking autophagy in advanced atherosclerosis. Our study thus suggests that the P2RY12 receptor is a therapeutic target for treating atherosclerosis.Abbreviations: 2-MeSAMP: 2-methylthioadenosine 5'-monophosphate; 8-CPT-cAMP: 8-(4-chlorophenylthio)-adenosine-3',5'-cyclic-monophosphate; ABCA1: ATP binding cassette subfamily A member 1; ABCG1: ATP binding cassette subfamily G member 1; ACTB: actin beta; ADPßs: adenosine 5'-(alpha, beta-methylene) diphosphate; ALs: autolysosomes; AMPK: AMP-activated protein kinase; APOA1: apolipoprotein A1; APs: autophagosomes; ATG5: autophagy related 5; ATV: atorvastatin; AVs: autophagic vacuoles; CD: chow diet; CDL: clopidogrel; CQ: chloroquine; DAPI: 4',6-diamidino-2-phenylindole; dbcAMP: dibutyryl-cAMP; DIL-oxLDL: dioctadecyl-3,3,3,3-tetramethylin docarbocyanine-oxLDL; EIF4EBP1/4E-BP1: eukaryotic translation initiation factor 4E binding protein 1; EVG: elastic van gieson; HE: hematoxylin-eosin; HDL: high-density lipoprotein; HFD: high-fat diet; KEGG: Kyoto Encyclopedia of Genes and Genomes; LDL-c: low-density lipoprotein cholesterol; LDs: lipid droplets; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; Masson: masson trichrome; MCPT: maximal carotid plaque thickness; MK2206: MK-2206 2HCL; NBD-cholesterol: 22-(N-[7-nitrobenz-2-oxa-1,3-diazol-4-yl] amino)-23,24-bisnor-5-cholen-3ß-ol; OLR1/LOX-1: oxidized low density lipoprotein receptor 1; ORO: oil Red O; ox-LDL: oxidized low-density lipoprotein; SQSTM1/p62: sequestosome 1; TEM: transmission electron microscopy; TIC: ticagrelor; ULK1: unc-51 like autophagy activating kinase 1; VSMCs: vascular smooth muscle cells.
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Aterosclerosis/patología , Autofagia , Células Espumosas/patología , Músculo Liso Vascular/patología , Miocitos del Músculo Liso/patología , Receptores Purinérgicos P2Y12/metabolismo , Animales , Atorvastatina/farmacología , Autofagia/efectos de los fármacos , Colesterol/metabolismo , Clopidogrel/farmacología , Sinergismo Farmacológico , Femenino , Células Espumosas/efectos de los fármacos , Células Espumosas/metabolismo , Células Espumosas/ultraestructura , Humanos , Lipólisis/efectos de los fármacos , Lisosomas/efectos de los fármacos , Lisosomas/metabolismo , Masculino , Ratones , Persona de Mediana Edad , Miocitos del Músculo Liso/efectos de los fármacos , Miocitos del Músculo Liso/metabolismo , Miocitos del Músculo Liso/ultraestructura , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal , Serina-Treonina Quinasas TOR/metabolismoRESUMEN
We investigated if corilagin can ameliorate or reverse atherosclerotic development via the toll-like receptor 4 (TLR4) signaling pathway in vitro and in vivo. Ana-1 cells or mouse peritoneal macrophages (MPMs) were stimulated with oxidized low-density lipoprotein followed by corilagin treatment. TLR4 expression in Ana-1 cells was upregulated by lentiviral transduction and downregulated by small interfering RNA. Peripheral blood mononuclear cells (PBMCs), plasma samples, and femoral arteries were collected from rats exhibiting peripheral artery disease (PAD). mRNA and protein expression of TLR4 and downstream molecules were decreased significantly by corilagin treatment in Ana-1 cells, MPMs, and rat PBMCs, and the reduction remained irrespective of downregulation or upregulation of TLR4 expression in Ana-1 cells. Corilagin also exerted a prominent effect on changes in plasma levels of cytokines and the pathologic manifestation of atherosclerosis in femoral arteries. Corilagin could ameliorate the development of atherosclerotic plaques by inhibiting the TLR4 signaling pathway in monocyte/macrophages and reduce the release of proinflammatory cytokines. This study provides a new therapeutic target and new niche targeting drug to oppose atherosclerosis and reveals the enormous potential of corilagin for control of PAD in humans.
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Glucósidos/farmacología , Taninos Hidrolizables/farmacología , Enfermedad Arterial Periférica/etiología , Enfermedad Arterial Periférica/metabolismo , Transducción de Señal/efectos de los fármacos , Receptor Toll-Like 4/metabolismo , Animales , Aterosclerosis/tratamiento farmacológico , Aterosclerosis/etiología , Aterosclerosis/metabolismo , Aterosclerosis/patología , Biomarcadores , Línea Celular , Citocinas/metabolismo , Modelos Animales de Enfermedad , Regulación de la Expresión Génica/efectos de los fármacos , Inmunohistoquímica , Ligandos , Lipoproteínas LDL/metabolismo , Lipoproteínas LDL/farmacología , Ratones , Enfermedad Arterial Periférica/tratamiento farmacológico , Enfermedad Arterial Periférica/patología , Placa Aterosclerótica , Unión Proteica , ARN Interferente Pequeño , Ratas , Receptor Toll-Like 2/genética , Receptor Toll-Like 2/metabolismo , Receptor Toll-Like 4/genéticaRESUMEN
The IL-13Rα1 signaling pathway and M2 macrophages play crucial roles in schistosome egg-induced hepatic fibrosis via the expression of pro-fibrotic molecules. This study aims to investigate the inhibitory effect and mechanism of action of corilagin on schistosome egg-induced hepatic fibrosis via the IL-13Rα1 signaling pathway in M2 macrophages in vitro and in vivo. The mRNA and protein expression of IL-13Rα1, PPARγ, KLF4, SOCS1, STAT6, p-STAT6, and TGF-ß was measured in vitro with corilagin treatment after IL-13 stimulation and in vivo corilagin treatment after effectively killing the adult schistosomes in schistosome-infected mice. Histological analysis of liver tissue was assessed for the degree of hepatic fibrosis. The results revealed that corilagin significantly reduced the expression of PPARγ, KLF4, SOCS1, p-STAT6, and TGF-ß compared with model group and praziquantel administration (p < 0.01 or p < 0.05) in vivo and in vitro, which indicated a strong inhibitory effect of corilagin on IL-13Rα1 signaling pathway. As well, the inhibitory effect of corilagin showed a significant dose-dependence (p < 0.05). The area of fibrosis and distribution of M2 macrophages in mouse liver tissue were reduced significantly and dose-dependently with corilagin treatment compared to model group or praziquantel administration (p < 0.01 or p < 0.05), indicating that corilagin suppressed IL-13Rα1 signaling pathway and M2 macrophage polarization effectively in vivo. Furthermore, the anti-fibrogenic effect persisted even when IL-13Rα1 was up- or down-regulated in vitro. In conclusion, corilagin can suppress schistosome egg-induced hepatic fibrosis via inhibition of M2 macrophage polarization in the IL-13Rα1 signaling pathway.
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Glucósidos/farmacología , Taninos Hidrolizables/farmacología , Subunidad alfa1 del Receptor de Interleucina-13/antagonistas & inhibidores , Cirrosis Hepática Experimental/tratamiento farmacológico , Cirrosis Hepática Experimental/parasitología , Macrófagos/efectos de los fármacos , Schistosoma/patogenicidad , Esquistosomiasis/tratamiento farmacológico , Animales , Antihelmínticos/uso terapéutico , Biomarcadores/análisis , Línea Celular , Glucósidos/uso terapéutico , Taninos Hidrolizables/uso terapéutico , Subunidad alfa1 del Receptor de Interleucina-13/genética , Subunidad alfa1 del Receptor de Interleucina-13/metabolismo , Factor 4 Similar a Kruppel , Macrófagos/inmunología , Masculino , Ratones , Ratones Endogámicos C57BL , Praziquantel/uso terapéutico , ARN Interferente Pequeño/genéticaRESUMEN
Deep Vein Thrombosis (DVT) has been known as a common medical problem all over the world. Thrombus traveling in blood vessels may lead to pulmonary embolism (PE), associated with high rates of mortality. Anticoagulant therapy is the mainstay treatment of DVT. Common anticoagulants, Vitamin K antagonists (VKAs), unfractionated heparin (UFH) and Low-molecular-weight heparin (LMWH) have been used in clinical application over decades, but can increase the risk of hemorrhage. Thereby, several new oral anticoagulants (NOACs) have been developed, which includes direct thrombin inhibitors (DTI) and direct factor Xa inhibitors. To be contrast with VKAs and UFH, NOACs have many advantages such as rapid offset action, few drug/food interactions and no need for routine coagulation monitoring, etc. Many NOACs are still being evaluated in Phase III clinical trials such as Betrixaban and Darexaban (YM150). However, NOACs still have problems to be solved such as lack of antidotes and laboratory monitoring, high drug costs, etc. Besides, several agents have already shown the potential to be new anticoagulants. Factor Xa play an important role in thrombin generation and coagulation pathway. Thus, the new compounds directly targeting on factor Xa for prevention DVT are highly anticipated. DPC423, a new series of 6-substituted coumarin derivatives and Phenyltriazolinones as potent factor Xa inhibitors have been recently reported. Recent studies revealed that agents extracted from botanicals not only have anti-coagulant effects but also possess other pharmacological activities such as anti-inflammation to alleviate the post-thrombotic syndromes. All the evidence above suggests that many new compounds might have great potential to be more effective and safe oral anticoagulants.
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Anticoagulantes/farmacología , Anticoagulantes/uso terapéutico , Cumarinas/farmacología , Inhibidores del Factor Xa/farmacología , Triazoles/farmacología , Trombosis de la Vena/tratamiento farmacológico , Anticoagulantes/administración & dosificación , Anticoagulantes/química , Cumarinas/administración & dosificación , Cumarinas/química , Factor Xa/metabolismo , Inhibidores del Factor Xa/administración & dosificación , Inhibidores del Factor Xa/química , Humanos , Triazoles/administración & dosificación , Triazoles/químicaRESUMEN
Normal pregnancy is associated with systemic vasodilation and decreased vascular contraction, partly due to increased release of endothelium-derived vasodilator substances. Endothelin-1 (ET-1) is an endothelium-derived vasoconstrictor acting via endothelin receptor type A (ETA R) and possibly type B (ETB R) in vascular smooth muscle cells (VSMCs), with additional vasodilator effects via endothelial ETB R. However, the role of ET-1 receptor subtypes in the regulation of vascular function during pregnancy is unclear. We investigated whether the decreased vascular contraction during pregnancy reflects changes in the expression/activity of ETAR and ETBR. Contraction was measured in single aortic VSMCs isolated from virgin, mid-pregnant (mid-Preg, day 12), and late-Preg (day 19) Sprague-Dawley rats, and the mRNA expression, protein amount, tissue and cellular distribution of ETAR and ETBR were examined using RT-PCR, Western blots, immunohistochemistry, and immunofluorescence. Phenylephrine (Phe, 10(-5) M), KCl (51 mM), and ET-1 (10(-6) M) caused VSMC contraction that was in late-Preg < mid-Preg and virgin rats. In VSMCs treated with ETB R antagonist BQ788, ET-1 caused significant contraction that was still in late-Preg < mid-Preg and virgin rats. In VSMCs treated with the ETAR antagonist BQ123, ET-1 caused a small contraction; and the ETBR agonists IRL-1620 and sarafotoxin 6c (S6c) caused similar contraction that was in late-Preg < mid-Preg and virgin rats. RT-PCR revealed similar ETAR, but greater ETBR mRNA expression in pregnant versus virgin rats. Western blots revealed similar ETAR, and greater protein amount of ETBR in endothelium-intact vessels, but reduced ETBR in endothelium-denuded vessels of pregnant versus virgin rats. Immunohistochemistry revealed prominent ETBR staining in the intima, but reduced ETAR and ETBR in the aortic media of pregnant rats. Immunofluorescence signal for ETAR and ETBR was less in VSMCs of pregnant versus virgin rats. The pregnancy-associated decrease in ETAR- and ETBR-mediated VSMC contraction appears to involve downregulation of ETAR and ETBR expression/activity in VSM, and may play a role in the adaptive vasodilation during pregnancy.
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Adaptación Fisiológica/fisiología , Regulación de la Expresión Génica/fisiología , Músculo Liso Vascular/citología , Miocitos del Músculo Liso/metabolismo , Receptor de Endotelina A/metabolismo , Receptor de Endotelina B/metabolismo , Animales , Aorta/citología , Estro , Femenino , Embarazo , Ratas , Ratas Sprague-Dawley , Receptor de Endotelina A/genética , Receptor de Endotelina B/genéticaRESUMEN
OBJECTIVE: Peripheral arterial disease (PAD) is a chronic occlusive disease mainly occurred in elderly adults. Arteriosclerosis obliterans (ASO) mainly occurring from small or medium sized arteries of the lower extremities is one of the most common causes of PAD. The gender-related differences of circulating risk factors in diabetic patients with ASO in China remain unknown. The aim of this study is to investigate the gender-related differences in the pattern of several potential risk factors between male and female patients with ASO and type 2 diabetes mellitus (T2D). DESIGN AND METHODS: Clinical profiles and risk factors were analyzed in 323 Chinese patients with ASO and 112 patients were confirmed with T2D. Severities of limb ischemia were staged according to Fontaine classification. RESULTS: The significant inverse correlation was seen between the increased age and hemoglobin. The significant positive correlation was seen between the increased age, urea and creatinine both in the non-diabetic and diabetic male patients. The expression levels of hemoglobin significantly correlate with the classification of Fontaine clinical symptoms in Chinese male patients with T2D/ASO. CONCLUSION: The study is the first report indicating that the gender-related differences of circulating risk factors are associated with T2D patients with ASO in China. Anemia in Chinese male patients with T2D/ASO may play an important role in peripheral arterial disease progression.
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Anemia/complicaciones , Pueblo Asiatico , Diabetes Mellitus Tipo 2/complicaciones , Progresión de la Enfermedad , Enfermedad Arterial Periférica/complicaciones , Enfermedad Arterial Periférica/patología , Adulto , Anciano , Anciano de 80 o más Años , China , Demografía , Femenino , Hemoglobinas/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Estadísticas no ParamétricasRESUMEN
Pregnancy is associated with uteroplacental and vascular remodeling in order to adapt for the growing fetus and the hemodynamic changes in the maternal circulation. We have previously shown upregulation of uterine matrix metalloproteinases (MMPs) during pregnancy. Whether pregnancy-associated changes in MMPs are localized to the uterus or are generalized in feto-placental and maternal circulation is unclear. Also, the mechanisms causing the changes in uteroplacental and vascular MMPs during pregnancy are unclear. MMPs expression, activity and tissue distribution were measured in uterus, placenta and aorta of virgin, mid-pregnant (mid-Preg) and late pregnant (late-Preg) rats. Western blots and gelatin zymography revealed increases in MMP-2 and -9 in uterus and aorta of late-Preg compared with virgin and mid-Preg rats. In contrast, MMP-2 and -9 were decreased in placenta of late-Preg versus mid-Preg rats. Extracellular MMP inducer (EMMPRIN) was increased in uterus and aorta of pregnant rats, but was less in placenta of late-Preg than mid-Preg rats. Prolonged treatment of uterus or aorta of virgin rats with 17ß-estradiol and progesterone increased the amount of EMMPRIN, MMP-2 and -9, and the sex hormone-induced increases in MMPs were prevented by EMMPRIN neutralizing antibody. Immunohistochemistry revealed that MMP-2 and -9 and EMMPRIN increased in uterus and aorta of pregnant rats, but decreased in placenta of late-Preg versus mid-Preg rats. Thus pregnancy-associated upregulation of uterine MMPs is paralleled by increased vascular MMPs, and both are mediated by EMMPRIN and induced by estrogen and progesterone, suggesting similar role of MMPs in uterine and vascular tissue remodeling and function during pregnancy. The decreased MMPs and EMMPRIN in placenta of late-Preg rats suggests reduced role of MMPs in feto-placental circulation during late pregnancy.
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Basigina/genética , Inducción Enzimática/efectos de los fármacos , Estradiol/farmacología , Metaloproteinasa 2 de la Matriz/genética , Metaloproteinasa 9 de la Matriz/genética , Preñez , Progesterona/farmacología , Animales , Aorta/efectos de los fármacos , Aorta/enzimología , Basigina/metabolismo , Femenino , Edad Gestacional , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Placenta/efectos de los fármacos , Placenta/enzimología , Embarazo , Ratas , Ratas Sprague-Dawley , Útero/efectos de los fármacos , Útero/enzimologíaRESUMEN
Thromboangiitis obliterans (TAO), also known as Buerger's disease, is segmental non-atherosclerotic inflammatory disease, which affects the small and medium-sized peripheral arteries, veins and nerves of young adult smokers. The paper reports two TAO female patients, 26-year-old and 42-year-old, with prolonged clotting time. We compared 13 male patients and 2 female patients with TAO. The prothrombin time (PT), activated partial thromboplastin time (APTT) and thrombin time (TT) were normal in the male patients, whereas the clotting times were prolonged in the female patients. Coagulation tests including PT, APTT and TT evaluation could be the potential markers to female patients with TAO.
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Tiempo de Tromboplastina Parcial , Tiempo de Protrombina , Tiempo de Trombina , Tromboangitis Obliterante/fisiopatología , Adulto , Femenino , Humanos , MasculinoRESUMEN
BACKGROUND AND PURPOSE: Normal pregnancy is associated with decreased vascular resistance and increased release of vasodilators. Endothelin-1 (ET-1) causes vasoconstriction via endothelin receptor type A (ET(A)R), but could activate ET(B)R in the endothelium and release vasodilator substances. However, the roles of ET(B)R in the regulation of vascular function during pregnancy and the vascular mediators involved are unclear. EXPERIMENTAL APPROACH: Pressurized mesenteric microvessels from pregnant and virgin Sprague-Dawley rats were loaded with fura-2/AM for simultaneous measurement of diameter and [Ca²âº]i. KEY RESULTS: High KCl (51 mM) and phenylephrine (PHE) caused increases in vasoconstriction and [Ca²âº]i that were similar in pregnant and virgin rats. ET-1 caused vasoconstriction that was less in pregnant than virgin rats, with small increases in [Ca²âº]i. Pretreatment with the ET(B)R antagonist BQ-788 caused greater enhancement of ET-1-induced vasoconstriction in pregnant rats. ACh caused endothelium-dependent relaxation and decreased [Ca²âº]i, and was more potent in pregnant than in virgin rats. ET-1 + ET(A)R antagonist BQ-123, and the ET(B)R agonists sarafotoxin 6c (S6c) and IRL-1620 caused greater vasodilation in pregnant than in virgin rats with no changes in [Ca²âº]i, suggesting up-regulated ET(B)R-mediated relaxation pathways. ACh-, S6c- and IRL-1620-induced relaxation was reduced by the NO synthase inhibitor Nω-nitro-L-arginine methyl ester, and abolished by tetraethylammonium or endothelium removal. Western blots revealed greater amount of ET(B)R in intact microvessels of pregnant than virgin rats, but reduced levels in endothelium-denuded microvessels, supporting a role of endothelial ET(B)R. CONCLUSIONS AND IMPLICATIONS: The enhanced ET(B)R-mediated microvascular relaxation may contribute to the decreased vasoconstriction and vascular resistance during pregnancy.
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Señalización del Calcio , Arterias Mesentéricas/fisiología , Venas Mesentéricas/fisiología , Microvasos/fisiología , Receptor de Endotelina B/metabolismo , Regulación hacia Arriba , Vasodilatación , Animales , Señalización del Calcio/efectos de los fármacos , Regulación hacia Abajo/efectos de los fármacos , Antagonistas de los Receptores de la Endotelina A , Endotelina-1/agonistas , Endotelina-1/antagonistas & inhibidores , Endotelina-1/metabolismo , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/enzimología , Endotelio Vascular/fisiología , Femenino , Técnicas In Vitro , Arterias Mesentéricas/efectos de los fármacos , Arterias Mesentéricas/enzimología , Venas Mesentéricas/efectos de los fármacos , Venas Mesentéricas/enzimología , Microvasos/efectos de los fármacos , Microvasos/enzimología , Óxido Nítrico Sintasa de Tipo III/antagonistas & inhibidores , Óxido Nítrico Sintasa de Tipo III/metabolismo , Embarazo , Ratas , Ratas Sprague-Dawley , Receptor de Endotelina A/agonistas , Receptor de Endotelina A/metabolismo , Receptor de Endotelina B/química , Regulación hacia Arriba/efectos de los fármacos , Resistencia Vascular/efectos de los fármacos , Vasoconstricción/efectos de los fármacos , Vasoconstrictores/farmacología , Vasodilatación/efectos de los fármacos , Vasodilatadores/farmacologíaRESUMEN
The etiology of deep vein thrombosis (DVT) is still not elucidated nowadays. Based on the accordance between DVT incidence and the anemophilous pollen concentration in the air, we proposed the hypothesis that allergic reaction induced by anemophilous pollen may cause "idiopathic" DVT, and proinflammatory factors may play an important role in the thrombosis process.
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Polen/efectos adversos , Trombosis de la Vena/etiología , Humanos , IncidenciaRESUMEN
The general characteristics, outcomes and risk factors of the patients with aortic dissection (AD) were evaluated in a single medical center. From January 2002 to December 2008, 284 patients with AD were treated and followed-up at our institution, including 105 cases of type A AD and 179 cases of type B AD. The patients in each type were divided into three groups according to management: medical treatment group (A or B), open surgery group (A or B), and stent-graft group (A or B). The characteristics and follow-up outcomes were compared between the groups or subgroups. The results showed that there was significant difference in the prognosis for type A AD between medical treatment group and open surgery group, but there was no significant difference in the prognosis for type B AD between medical treatment group and stent-graft group. Independent risk factors of follow-up mortality for patients with type A AD included a history of atherosclerosis (HR, 3.807; 95% confidence interval [CI], 1.489 to 7.611; P=0.003), in-hospital hypotension/shock (HR, 4.687; 95% CI, 1.846 to 11.900; P=0.001), in-hospital myocardial ischemia or infarction (HR, 3.734; 95% CI, 1.613 to 8.643; P=0.002), pleural effusion (HR, 2.210; 95% CI, 1.080 to 4.521; P=0.030), branch vessel involvement (HR, 2.747; 95% CI, 1.202 to 6.278; P=0.016) and surgical treatment (HR, 0.177; 95% CI, 0.063 to 0.502; P=0.001). And there were insignificant independent predictors for mortality of the patients with type B AD. It was concluded that there were significant differences in characteristics and one year mortality between type A AD and type B AD, but after one year, there was no significant difference in the mortality and complications of them. There were several discordant risk factors of AD, such as female gender, age, thrombus, abrupt onset of pain that were considered as the risk factors in some papers. And there was no definite risk factor of mortality in this study in the patients with type B AD.