RESUMEN
Drug resistance caused by the extreme genetic variability of zhe hepatitis C virus has rendered effective combinations of drugs indispensable in the treatment of chronic hepatitis C (CHC). Herein, we developed a fixed-dose combination (FDC) treatment containing the NS5B inhibitor sofosbuvir (SOF) and the NS5A inhibitor fopitasvir (FOP). Then the dissolution behavior of FOP in FOP/SOF FDC was improved by co-micronizing FOP with lactose. The enhanced dissolution rate of FOP in the FDC was in good agreement with the behavior of the FOP singledrug tablet. In addition, pharmacokinetic studies showed that both FOP and SOF in the FDC exhibited similar characteristics (area under the curve, Cmax, Tmax, and T1/2) as those of tablets containing FOP or SOF alone. These results revealed that the FOP/SOF FDC represents a potential therapeutic option for the treatment of CHC.
Asunto(s)
Hepatitis C Crónica , Sofosbuvir , Antivirales/farmacología , Antivirales/uso terapéutico , Hepacivirus/genética , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Sofosbuvir/farmacología , Sofosbuvir/uso terapéutico , ComprimidosRESUMEN
To explore the protective effect of naringin(Nar) on the injury of myocardium tissues induced by streptozotocin(STZ) in diabetic rats and the relationship with oxidative stress and endoplasmic reticulum stress(ERS)ï¼ the male SD rats were intraperitoneally injected with streptozotocin(STZï¼ 60 mg·kg⻹) to establish the diabetic rat model and then randomly divided into the type 1 diabetic rat group(T1DR)ï¼ the low-dose Nar group(Nar25)ï¼ the middle-dose Nar group(Nar50) and the high-dose Nar group(Nar100). The normal rats were designed as control group(Con). Nar25ï¼ Nar50ï¼ Nar100 groups were orally administered with Nar at the doses of 25.0ï¼ 50.0ï¼ 100.0 mg·kg⻹ per dayï¼ respectivelyï¼ while the normal group and the T1DR group were orally administered with saline. At the 8th week after treatmentï¼ fasting plasma glucose and heart mass index were measured. The pathological changes in myocardial tissues were observed by microscope. The cardiac malondialdehyde(MDA) level and superoxide dismutase(SOD) activities were measured. The gene and protein expressions of glucose-regulated protein 78(GRP78)ï¼ C/EBP homologous protein(CHOP)ï¼ cysteinyl aspartate-specific proteinase 12(caspase 12) were detected by qRT-PCR and Western blot. According to the resultsï¼ compared with control groupï¼ the myocardial structure was damagedï¼ the content of MDA was increasedï¼ while the activities of SOD were decreased(P<0.05) in T1DR group. GRP78ï¼ CHOP and caspase 12 mRNA and protein expressions were increased significantly in T1DR group(P<0.05ï¼ P<0.01). Compared with T1DR groupï¼ myocardial structure damage was alleviated in Nar treatment group. The content of MDA was decreasedï¼ while the activities of SOD were increased significantly. The mRNA and protein expressions of GRP78ï¼ CHOP and caspase 12 were increasedï¼ especially in middle and high-dose groups(P<0.05ï¼ P<0.01). After treatment with Nar for 8 weeksï¼ myocardial structure damage was obviously alleviated in Nar treatment groups. The content of MDA was decreasedï¼ while the activities of SOD were increased significantly in myocardial tissues. The mRNA and protein expressions of GRP78ï¼ CHOP and caspase 12 were increasedï¼ especially in middle and high-dose groups(P<0.05ï¼ P<0.01). The findings suggest that Nar may protect myocardium in diabetic rats by reducing mitochondrial oxidative stress injuries and inhibiting the ERS-mediated cell apoptosis pathway.
Asunto(s)
Cardiotónicos/farmacología , Cardiomiopatías Diabéticas/tratamiento farmacológico , Estrés del Retículo Endoplásmico/efectos de los fármacos , Flavanonas/farmacología , Estrés Oxidativo/efectos de los fármacos , Animales , Apoptosis , Caspasa 12/metabolismo , Diabetes Mellitus Experimental , Proteínas de Choque Térmico/metabolismo , Masculino , Malondialdehído/metabolismo , Ratas , Ratas Sprague-Dawley , Superóxido Dismutasa/metabolismo , Factor de Transcripción CHOP/metabolismoRESUMEN
There are two independent mol-ecules in the asymmetric unit of the title compound, C(22)H(21)N(3)O(4)S. The central benzene ring makes dihedral angles of 74.28â (6) and 68.84â (6)° with the pyridine and 3,5-dimeth-oxy-phenyl rings, respectively, in one molecule [86.66â (6) and 81.14â (6)° respectively, in the other]. Each of the mol-ecules forms a centrosymmetric dimer with another mol-ecule via pairs of inter-molecular N-Hâ¯O hydrogen bonds. These hydrogen bonds connect the N-H groups and the O atoms of the carbonyl groups next to the 3,5-dimeth-oxy-phenyl rings. Additional inter-molecular N-Hâ¯O inter-actions link the dimers in the crystal structure.
RESUMEN
RATIONALE: Agenesis of the dorsal pancreas (ADP) is a rare congenital anomaly of the pancreas. ADP is associated with some other medical problems such as diabetes mellitus, abdominal pain/bloating, pancreatitis, pancreatic neuroendocrine tumor and so on. In this study, we present a case of ADP with chronic suppurative pancreatitis, summarize the clinical characteristics of the reported cases in China and review the correlative literature. PATIENT CONCERNS: A 51-year-old Chinese man, with a history of impaired fasting glucose, presented with jaundice, pruritus and dark urine. Laboratory analysis showed abnormal liver function and elevated carbohydrate antigen 19-9. DIAGNOSES: Contrast-enhanced computed tomography demonstrated a mass located at the head of pancreas and complete absence of the body and tail of pancreas. Endoscopic retrograde cholangiopancreatography demonstrated an eccentric malignant stricture about 1.6cm of distal common bile duct. INTERVENTIONS: The patient underwent pancreaticoduodenectomy because of the suspicion of pancreatic tumor. The postoperative pathological result was chronic suppurative pancreatitis, with moderate hyperplasia in focal ductal epithelium. OUTCOMES: A long-term follow-up shows that the patient is asymptomatic with well-controlled diabetes mellitus and pancreatic exocrine insufficiency. LESSONS: ADP is a quite rare congenital malformation of the pancreas with poorly-understood pathogenesis. The diagnosis of ADP depends on the imaging examination. The therapeutic strategy varies from person to person due to the different accompanying conditions.
Asunto(s)
Anomalías Congénitas , Páncreas/anomalías , Páncreas/diagnóstico por imagen , Pancreatitis Crónica/complicaciones , Colangiopancreatografia Retrógrada Endoscópica , Humanos , Masculino , Persona de Mediana Edad , Páncreas/cirugía , Pancreaticoduodenectomía , Pancreatitis Crónica/diagnóstico , Tomografía Computarizada por Rayos XRESUMEN
Supercritical fluid extraction was applied to obtain the lower polarity extracts from Croton crassifolius roots, and chemical investigation of which led to the isolation and identification of two new diterpenoids, named crassifolius P (1) and crassifolius Q (2). In vitro anti-proliferative activities of compounds 1 and 2 on A549, Hep-G2 and Hela tumor cell lines were evaluated. The two new compounds exhibited obvious selectivity to tumor cells with IC50 values ranging from 20.43 ± 1.18 µM to 25.72 ± 1.32 µM.
Asunto(s)
Cromatografía con Fluido Supercrítico , Croton , Diterpenos , Línea Celular Tumoral , Diterpenos/farmacología , Estructura Molecular , Raíces de PlantasRESUMEN
The asymmetric unit of the title compound, C(21)H(17)F(3)N(3)O(3) (+)·C(7)H(7)O(3)S(-)·H(2)O, contains two formula units. In one of the cations, the pyridinium and trifluoro-methyl benzene rings form dihedral angles of 87.42â (8) and 45.92â (8)°, respectively, with the central benzene ring [79.56â (8) and 43.52â (8)° in the other cation]. In the crystal structure, N-Hâ¯O, O-Hâ¯O and C-Hâ¯O hydrogen bonds link the ions and water mol-ecules, forming a three-dimensional network.
RESUMEN
In the title compound, C(21)H(19)N(3)O(4), the central benzene ring makes dihedral angles of 78.54â (6) and 75.30â (6)° with the pyridine and 3-methoxy-phenyl rings, respectively. An intra-molecular N-Hâ¯N interaction occurs, generating an S(?). The crystal packing shows inter-molecular N-Hâ¯O hydrogen-bonding inter-actions between the N-H groups and the O atoms of the 3-methoxy-phenyl ring and the carbonyl groups of the amide functions. Inter-molecular C-Hâ¯O inter-actions are also present.
RESUMEN
PDB-1 is a new C-27-carboxylated-lupane-triterpenoid derivative isolated from Potentilla discolor Bunge. In our previous research, PDB-1 was suggested to have an obvious selectivity for tumor cells. This study focused on clarifying PDB-1's anticancer mechanism in the inhibition of proliferation and in the induction of apoptosis and autophagy in A549 cells. In general, A549 cells were treated with PDB-1 for different times, and cell survival was assessed by a CCK8 assay. The assessment of intracellular reactive oxygen species, a mitochondrial membrane potential assay, a cell cycle assay, an annexin V-FITC/PI assay, and MDC staining were performed in A549 cells treated with PDB-1. Moreover, the mRNA and protein expression of cell cycle-, apoptosis- and autophagy-related factors were detected by RT-qPCR and western blotting. The results showed that PDB-1 inhibited A549 cell proliferation and colony formation in a dose- and time-dependent manner. The decrease in the viability of A549 cells was due to a G2/M cell cycle arrest. Moreover, PDB-1 induced cell apoptosis, accompanied by an increase in the Bax/Bcl-2 ratio and an increase in the expression levels of cleaved caspase-3/caspase-9. We also found that PDB-1 induced autophagy by increasing the conversion of LC3-I to LC3-II and elevating Beclin-1. In addition, further studies indicated that pretreatment with a specific PI3K inhibitor (LY294002) enhanced the effects of PDB-1 on the expression of proteins associated with apoptosis and autophagy, demonstrating that the PI3K/Akt/mTOR pathway was related to PDB-1-induced apoptosis and autophagy. These results indicated that PDB-1 may be considered a potential candidate for the future treatment of lung adenocarcinoma. These findings should benefit the development of the C14-COOH type of pentacyclic triterpenoids.