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1.
BMC Complement Med Ther ; 21(1): 33, 2021 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-33446171

RESUMO

BACKGROUND: Microcirculatory disturbance is closely associated with multiple diseases such as ischemic and septic stroke. Luteolin (3,4,5,7-tetrahydroxyflavone) is a vascular protective flavonoid present in several dietary foods. However, how luteolin plays a role in microcirculatory disturbance is still unknown. The purpose of this study was to find out the influence of luteolin on the lipopolysaccharide (LPS)-induced microcirculatory disturbance, focusing on its effect on leukocyte adhesion and the underlying mechanism of this effect. METHODS: After injecting LPS into rats, we used an inverted intravital microscope to observe the velocity of red blood cells in venules, numbers of leukocytes adherent to and emigrated across the venular wall, hydrogen peroxide production in venular walls and mast cell degranulation. Intestinal microcirculation blood flow was measured by High-resolution Laser Doppler Perfusion Imaging. Histological changes of small intestine and mesenteric arteries were evaluated. Additionally, cell adhesion stimulated by LPS was tested on EA.hy926 and THP-1 cells. The production of pro-inflammatory cytokines, adhesion molecules and the activation of TLR4/Myd88/NF-κB signaling pathway were determined. RESULTS: The results showed luteolin significantly inhibited LPS-induced leukocyte adhesion, hydrogen peroxide production and mast cell degranulation, and increased intestinal microcirculation blood flow and ameliorated pathological changes in the mesenteric artery and the small intestine. Furthermore, luteolin inhibited the release of pro-inflammatory cytokines, the expression of TLR4, Myd88, ICAM-1, and VCAM-1, the phosphorylation of IκB-α and NF-κB/p65 in LPS stimulated EA.hy926. CONCLUSIONS: Our findings revealed that it is likely that luteolin can ameliorate microcirculatory disturbance. The inhibitory effects of luteolin on the leukocyte adhesion stimulated by LPS, which participates in the development of microcirculatory disturbance, are mediated through the regulation of the TLR4/Myd88/NF-κB signaling pathway.

2.
Curr Drug Targets ; 2021 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-33504304

RESUMO

Systemic chemotherapy and radiotherapy have been widely used in clinics for several decades, but their disadvantages, such as systemic cytotoxicity and severe side effects, are the biggest obstacle to maximum therapeutic efficacy. In recent years, the impact of extracellular matrix components in tumor progression has aroused the attention of researchers, and with the rapid development of nanomaterials, extracellular matrix targeted nanomaterials have become a promising strategy in tumor theranostics. In this review, we are going to outline the recent and relevant examples of various tumor extracellular matrix targeted nanomaterials applied in tumor therapy and imaging. And we will discuss the challenges and prospects of nanomaterials for future tumor therapy.

3.
Cancer Manag Res ; 12: 11095-11102, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33173342

RESUMO

Background: Mitochondrial fission regulator 2 (MTFR2) has been reported to promote proliferation, migration and invasion in tumors; however, little is known about its function in breast cancer. Thus, we investigated the effect of MTFR2 expression on prognosis of breast cancer. Methods: The expression of MTFR2 in breast cancer tissues was detected by immunohistochemistry, and overall survival (OS) and recurrence free survival (RFS) were evaluated by the Log rank test and Cox model. Results: We found that MTFR2 expression was significantly associated with clinical stage (P<0.001), T classification (P=0.005), N classification (P=0.001), M classification (P=0.041), HER2 expression (P= 0.001), and molecular subtypes (P=0.002), respectively. Compared with low MTFR2 expression, the patients with higher expression of MTFR2 exhibited significantly shorter OS and RFS (All P < 0.001). Both univariate and multivariate analyses showed that MTFR2 was an independent prognostic factor for OS (HR, 2.8, 95% CI 1.1-6.8, P = 0.023) and RFS (HR, 2.8, 95% CI 1.2-6.4, P = 0.015) in breast cancer patients. Moreover, in HER2 positive and TNBC subtype, the associations between high MTFR2 expression and poor OS and RFS were more pronounced. Conclusion: Taken together, our results demonstrated that high MTFR2 expression was associated with poor prognosis of breast cancer patients, and such an association was more pronounced in the patients with aggressive tumors. Therefore, MTFR2 expression might be a potentially important prognostic biomarker and clinical target for patients with breast cancer.

4.
Clin Cardiol ; 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33205849

RESUMO

BACKGROUND: Cryoballoon ablation (CBA) and radiofrequency ablation (RFA) are the most common procedures used to treat refractory atrial fibrillation (AF) and are performed through pulmonary vein isolation (PVI). Studies have shown that CBA can approximately match the therapeutic effects of RFA against AF. However, few studies have investigated the difference between CBA and RFA of the effects on left atrial remodeling for paroxysmal AF. OBJECTIVE: Atrial remodeling is considered pivotal to the occurrence and development of AF, therefore we sought to assess the influence of atrial remodeling in patients with paroxysmal AF after CBA and RFA in this study. METHODS: In this nonrandomized retrospective observational study, we enrolled 328 consecutive patients who underwent CBA or RFA for refractory paroxysmal AF in May 2014 to May 2017 in our hospital. After propensity score matching, 96 patients were included in the CBA group, and 96 were included in the RFA group. Patients were asked to undergo a 12-lead electrocardiogram, a 24-h Holter monitor, and an echocardiogram and to provide their clinical history and symptoms at 6 months and 1, 2, and 3 years postprocedurally. Electrical remodeling of the left atrium was assessed by P wave dispersion (Pdis); structural remodeling was assessed by the left atrium diameter (LAD) and left atrial volume index (LAVI) during scheduled visits. RESULTS: As of January 2020, compared with baseline, at 1 year, 2 years, and 3 years after ablation, the average changes in Pdis (∆Pdis), LAD (∆LAD), and LAVI (∆LAVI) were significant in both the CBA and RFA groups. Six months after ablation, ∆Pdis, ∆LAD, and ∆LAVI were greater in the CBA group than in the RFA group. There was no significant difference between the two groups in AF/flutter recurrence, but the AF/flutter-free survival time of CBA group may be longer than RFA group after 2 years after ablation. A higher ∆Pdis, ∆LAD, or ∆LAVI at 1 year after ablation may increase AF/flutter-free survival. CONCLUSIONS: Although CBA and RFA are both effective in left atrial electrical and structural reverse-remodeling in paroxysmal AF, CBA may outperform RFA for both purposes 6 months after ablation. However, during long-term follow-up, there was no significant intergroup difference.

5.
AAPS PharmSciTech ; 21(8): 316, 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33174133

RESUMO

Borneol can enhance the bioavailability of several other drugs by opening the blood-brain barrier and inhibiting P-glycoprotein (P-gp) efflux. However, whether borneol will impact the bioavailability and the mechanism of compound Danshen colon-specific osmotic pump capsule (CDCOPC) remains unclear. This study aimed to determine the effects of borneol on the in vitro release and in vivo pharmacokinetic characteristics of CDCOPC. Besides, the in vitro release behavior of CDCOPC was further assessed by chromatographic fingerprints. The in vitro release studies showed that borneol followed the zero-order release and hardly impacted the in vitro release of Salvia miltiorrhiza and Panax notoginseng in CDCOPC. Moreover, as revealed from the similarity results of fingerprints, the in vitro release of different components of CDCOPC was almost simultaneous. Compared with the commercially available tablets, the pharmacokinetics studies suggested that both CDCOPCs containing and lacking borneol could significantly prolong the retention time of these effective components; their average relative bioavailability values increased to 448.70% and 350.97%, respectively. Notably, borneol significantly improved the relative bioavailability of some components of CDCOPC, such as salvianolic acid B (SAB), tanshinone IIA (Tan IIA), notoginsenoside R1 (R1), ginsenoside Rg1 (Rg1), and ginsenoside Re (Re) from CDCOPC, while it slightly impacted ginsenoside Rb1 (Rb1) and ginsenoside Rd (Rd). Summarily, borneol is capable of improving the bioavailability of some effective components in CDCOPC, which is critical to design with CDCOPC for enhanced bioavailability. This study could also help reveal the composition principle of the compound Danshen formula (CDF).

6.
Drug Dev Ind Pharm ; 46(11): 1776-1786, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32895014

RESUMO

The aim of this study was to develop the Metformin Hydrochloride and Gliclazide (MH-GZ) sandwiched osmotic pump capsule which could overcome the problems associated with short half-life and burst release. The system could deliver drugs with different solubility simultaneously at zero-order rate, in which MH-GZ were filled in both sides of the push layer respectively. The single factor and orthogonal test were employed to obtain the optimized formulation with the evaluation index of similarity factor (ƒ2). R language was used to visualized analyze the main influence factors of drug release and their correlations. Pharmacokinetic study was performed in beagle dogs compared to the marketed conventional product, which showed decreased Cmax, prolonged Tmax, and improved bioavailability, independent of pH and agitational speed but related to osmotic pressure differences across the semi permeable membrane. The designed sandwiched osmotic pump capsule proposed a promising substitute for the marketed product for the treatment of type 2 diabetes.

7.
J Exp Bot ; 2020 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-32937662

RESUMO

Long non-coding RNAs (lncRNAs) play essential roles in plant abiotic stress responses, however, the lncRNA-mediated genetic networks response to cadmium (Cd) treatment remain elusive in trees, the promising phytoremediation candidates for Cd contamination. Here, we identified 172 Cd-responsive lncRNAs and 295 differentially expressed target genes in the leaves of Populus tomentosa under Cd treatment. Functional annotation revealed that these lncRNAs involved in various processes, including photosynthesis, hormone regulation, and phenylalanine metabolism. Association studies identified 78 significant associations, representing 14 Cd-responsive lncRNAs and 28 target genes for photosynthetic and leaf physiological traits. Epistasis uncovered 83 pairwise interactions among these traits, unveiling Cd-responsive lncRNA-mediated genetic networks for photosynthesis and leaf physiology in P. tomentosa. We then focused on the roles of two Cd-responsive lncRNA-gene pairs, MSTRG.22608.1-PtoMYB73 and MSTRG.5634.1-PtoMYB27, in Cd tolerance of Populus, and detected insertions/deletions within lncRNAs as polymorphisms driving target gene expression. LncRNAs genotype analysis and heterologous overexpressing PtoMYB73 and PtoMYB27 in Arabidopsis indicated their positive effects on enhancing Cd tolerance, photosynthetic rate, and leaf growth, and the potential interaction mechanisms of PtoMYB73 with abiotic stresses. Our study provides the genetic basis for Populus response to Cd treatment, facilitating genetic improvement of enhancing Cd tolerance in trees.

8.
Redox Biol ; 36: 101685, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32853879

RESUMO

NADPH is a pivotal cofactor that maintains redox homeostasis and lipogenesis in cancer cells and interference with NADPH production is a promising approach for treating cancer. However, how normal and cancer cells differentially exploit NADPH-producing pathways is unclear, and selective approaches to targeting NADPH are lacking. Here, we show that the assayed cancer cell lines preferentially depend on ME1-mediated NADPH production. ME1 knockdown increases intracellular ROS levels and impairs lipogenesis in cancer cells, leading to retarded proliferation and increased anoikis, while sparing normal cells. Notably, ME1 interference ultimately resulted in adaptive upregulation of mitochondrial IDH2 dependent of AMPK-FoxO1 activation to replenish the NADPH pool and mitigate cytosolic ROS. Combining ME1 ablation and IDH2 inhibition drastically reduces intracellular NADPH and prevents resistance to ME1 interference, resulting in increased apoptosis and impeded tumor growth and metastasis. This study demonstrates that cytosolic ME1 integrated with mitochondrial IDH2 is essential for tumor growth and metastasis, thereby highlighting the blockade of metabolic compensation by disrupting mitochondrial-cytosol NADPH transport as a promising approach to selectively targeting NADPH in cancer cells that rely on NADPH-driven antioxidant systems.

9.
FASEB J ; 34(10): 13474-13493, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32780898

RESUMO

Potential underlying molecular mechanisms for uric acid-induced lipid metabolic disturbances had not been elucidated clearly. This study investigated the effects and underlying mechanisms of uric acid on the development of lipid metabolic disorders. We collected blood samples from 100 healthy people and 100 patients with hyperuricemia for whom serum lipid analysis was performed. Meanwhile, a mouse model of hyperuricemia was generated, and lipidomics was performed on liver tissues, comparing control and hyperuricemia groups, to analyze lipid profiles and key metabolic enzymes. Uric acid directly induced serum lipid metabolic disorders in both humans and mice based on triglycerides, total cholesterol, and low-density lipoprotein cholesterol. Through lipidomic analysis, 46 lipids were differentially expressed in hyperuricemic mouse livers, and the phosphatidylcholine composition was altered, which was mediated by LPCAT3 upregulation. High-uric acid levels-induced p-STAT3 inhibition and SREBP-1c activation in vivo and in vitro. Moreover, LPCAT3-knockdown significantly attenuated uric acid-induced p-STAT3 inhibition, SREBP-1c activation, and lipid metabolic disorders in L02 cells. In conclusion, uric acid induces lipid metabolic disturbances through LPCAT3-mediated p-STAT3 inhibition and SREBP-1c activation. LPCAT3 could be a key regulatory factor linking hyperuricemia and lipid metabolic disorders. These results might provide novel insights into the clinical treatment of hyperuricemia.

10.
Mol Cancer ; 19(1): 98, 2020 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-32473645

RESUMO

BACKGROUND: Anti-angiogenic therapy represents a promising strategy for non-small-cell lung cancer (NSCLC) but its application in lung squamous cell carcinoma (SQC) is limited due to the high-risk adverse effects. Accumulating evidence indicates that long noncoding RNAs (lncRNAs) mediate in tumor progression by participating in the regulation of VEGF in NSCLC, which might guide the development of new antiangiogenic strategies. METHODS: Differential lncRNA expression in SQC was analyzed in AE-meta and TCGA datasets, and further confirmed in lung cancer tissues and adjacent normal tissues with RT-qPCR and in-situ hybridization. Statistical analysis was performed to evaluate the clinical correlation between LINC00173.v1 expression and survival characteristics. A tube formation assay, chick embryo chorioallantoic membrane assay and animal experiments were conducted to detect the effect of LINC00173.v1 on the proliferation and migration of vascular endothelial cells and tumorigenesis of SQC in vivo. Bioinformatics analysis, RNA immunoprecipitation and luciferase reporter assays were performed to elucidate the downstream target of LINC00173.v1. The therapeutic efficacy of antisense oligonucleotide (ASO) against LINC00173.v1 was further investigated in vivo. Chromatin immunoprecipitation and high throughput data processing and visualization were performed to identify the cause of LINC00173.v1 overexpression in SQC. RESULTS: LINC00173.v1 was specifically upregulated in SQC tissues, which predicted poorer overall and progression-free survival in SQC patients. Overexpression of LINC00173.v1 promoted, while silencing LINC00173.v1 inhibited the proliferation and migration of vascular endothelial cells and the tumorigenesis of SQC cells in vitro and in vivo. Our results further revealed that LINC00173.v1 promoted the proliferation and migration of vascular endothelial cells and the tumorigenesis of SQC cells by upregulating VEGFA expression by sponging miR-511-5p. Importantly, inhibition of LINC00173.v1 via the ASO strategy reduced the tumor growth of SQC cells, and enhanced the therapeutic sensitivity of SQC cells to cisplatin in vivo. Moreover, our results showed that squamous cell carcinoma-specific factor ΔNp63α contributed to LINC00173.v1 overexpression in SQC. CONCLUSION: Our findings clarify the underlying mechanism by which LINC00173.v1 promotes the proliferation and migration of vascular endothelial cells and the tumorigenesis of SQC, demonstrating that LINC00173.v1-targeted drug in combination with cisplatin may serve as a rational regimen against SQC.

11.
Nat Commun ; 11(1): 3134, 2020 06 19.
Artigo em Inglês | MEDLINE | ID: mdl-32561717

RESUMO

Physical neural networks made of analog resistive switching processors are promising platforms for analog computing. State-of-the-art resistive switches rely on either conductive filament formation or phase change. These processes suffer from poor reproducibility or high energy consumption, respectively. Herein, we demonstrate the behavior of an alternative synapse design that relies on a deterministic charge-controlled mechanism, modulated electrochemically in solid-state. The device operates by shuffling the smallest cation, the proton, in a three-terminal configuration. It has a channel of active material, WO3. A solid proton reservoir layer, PdHx, also serves as the gate terminal. A proton conducting solid electrolyte separates the channel and the reservoir. By protonation/deprotonation, we modulate the electronic conductivity of the channel over seven orders of magnitude, obtaining a continuum of resistance states. Proton intercalation increases the electronic conductivity of WO3 by increasing both the carrier density and mobility. This switching mechanism offers low energy dissipation, good reversibility, and high symmetry in programming.

12.
Hum Cell ; 33(4): 1336, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32557220

RESUMO

This article has been retracted by the editors because the data are unreliable. It appears that the images in Figure 4c have been re-used but labelled as different conditions. The authors were asked to provide raw data for this figure, but were unable to do so. Author Jianyang Chen stated on behalf of all co-authors that they agree to this retraction.

13.
Nan Fang Yi Ke Da Xue Xue Bao ; 40(1): 20-26, 2020 Jan 30.
Artigo em Chinês | MEDLINE | ID: mdl-32376564

RESUMO

OBJECTIVE: To investigate the effect of overexpression of leukemia inhibitory factor (LIF) on cisplatin and paclitaxel resistance of endometrial cancer cells in vitro. METHODS: Endometrial cancer cell lines HEC-1B and RL95-2 were infected with a recombinant lentivirus to overexpress LIF, and the changes in LIF expression was verified using RT-qPCR and ELISA. The viability of the LIF-overexpressing cells was assessed using CCK-8 assay, and the cell apoptosis and changes in mitochondrial membrane potential in response to cisplatin or paclitaxel treatment were analyzed with annexin V-FITC/PI staining and JC-1 assay, respectively. The effect of LIF overexpression on the expressions of Bcl-2 family proteins and STAT3 pathway was evaluated using Western blotting; dual-luciferase reporter gene assay was employed to detect the transcriptional activity of STAT3. The effect of STAT3 silencing on apoptosis of the LIF-overexpressing cells induced by cisplatin or paclitaxel was investigated. RESULTS: The cell lines infected with the recombinant lentivirus showed significantly increased mRNA and protein levels of LIF (P < 0.05) without obvious changes in the cell viability (P>0.05). LIF overexpression significantly attenuated cisplatin-or paclitaxel-induced apoptosis of the endometrial cancer cells (P < 0.05) and markedly increased mitochondrial membrane potential of the cells (P < 0.05). The expressions of Bcl-2, Bcl-xL and p-STAT3 proteins increased obviously while the expressions of Bax, Bad and STAT3 either decreased or showed no obvious changes in the LIF-overexpressing cells. Overexpressing LIF significantly enhanced the transcriptional activity of STAT3 (P < 0.05), and silencing STAT3 obviously enhanced apoptosis of the endometrial cancer cells overexpressing LIF (P < 0.05). CONCLUSIONS: s Overexpression of LIF can enhance cisplatin and paclitaxel resistance to endometrial cancer cells in vitro.


Assuntos
Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos , Neoplasias do Endométrio/genética , Fator Inibidor de Leucemia/genética , Paclitaxel/farmacologia , Transdução de Sinais , Antineoplásicos/farmacologia , Apoptose , Linhagem Celular Tumoral , Feminino , Humanos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Fator de Transcrição STAT3/metabolismo , Proteína bcl-X/metabolismo
14.
Biomed Pharmacother ; 128: 110274, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32464305

RESUMO

PURPOSE: Aggressively growing tumors are characterized by significant variations in metabolites, including lipids, and can involve the elevated synthesis ofde novo fatty acids. METHODS: Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS)-based metabolomics and lipidomics were performed to compare human gastric cancer tissues and adjacent normal tissues from clinical patients. A series of cellular and molecular biological methods were applied to validate the lipidomics results. RESULTS: Palmitic acid (PA) was found to be significantly downregulated in gastric cancer tissues, and it was found that a high concentration of PA specifically inhibited cell proliferation and impaired cell invasiveness and migrationin vitro in AGS, SGC-7901, and MGC-803 gastric cancer cell lines. Moreover, sterol regulatory element-binding protein 1 (SREBP-1c) was activated in human gastric cancer tissues, and it promoted the expression of a series of genes associated with the synthesis of fatty acids, such as SCD1 and FASN. SREBP-1c knockdown rescued the migration and invasion defects in AGS and SGC-7901 gastric cancer cells. CONCLUSION: Taken together, our findings confirmed the variation in fatty acid synthesis in gastric cancer and identified SREBP-1c as a promising target for gastric cancer treatment.

15.
Cancer Lett ; 482: 56-71, 2020 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-32289442

RESUMO

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death due to its early recurrence and widespread metastatic potential. Accumulating studies have reported that dysregulation of circadian rhythms-associated regulators is implicated in the recurrence and metastasis of NSCLC. Therefore, identification of metastasis-associated circadian rhythm genes is clinically necessary. Here we report that the circadian gene hepatic leukemia factor (HLF), which was dramatically reduced in early-relapsed NSCLC tissues, was significantly correlated with early progression and distant metastasis in NSCLC patients. Upregulating HLF inhibited, while silencing HLF promoted lung colonization, as well as metastasis of NSCLC cells to bone, liver and brain in vivo. Importantly, downexpression of HLF promoted anaerobic metabolism to support anchorage-independent growth of NSCLC cells under low nutritional condition by activating NF-κB/p65 signaling through disrupting translocation of PPARα and PPARγ. Further investigations revealed that both genetic deletion and methylation contribute to downexpression of HLF in NSCLC tissues. In conclusion, our results shed light on a plausible mechanism by which HLF inhibits distant metastasis in NSCLC, suggesting that HLF may serve as a novel target for clinical intervention in NSCLC.

16.
Pest Manag Sci ; 76(7): 2415-2422, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32056365

RESUMO

BACKGROUND: The beet armyworm, Spodoptera exigua, is a serious agricultural pest that is primarily controlled using chemical insecticides. Recently, resistance to the insecticide spinosad has been described in S. exigua field populations. To date, there has been no functional evidence proving the involvement of the nicotinic acetylcholine receptor (nAChR) α6 mutation in spinosad resistance in S. exigua. RESULTS: In this study, using the CRISPR/Cas9 genome-editing system, a homozygous strain (Seα6-KO) with approximately 1760-bp deletion within Seα6 in S. exigua causing a premature truncation of Seα6 was successfully constructed. Insecticide bioassays showed that Seα6-KO exhibited 373-fold higher resistance to spinosad and 850-fold higher resistance to spinetoram compared to WH-S strain with the same genetic background but showed no significant change in susceptibility to emamectin benzoate and chlorantraniliprole. Genetic analysis revealed that Seα6-KO is inherited as an incompletely recessive trait. CONCLUSION: The results clearly demonstrated the functional role of Seα6 in resistance to spinosyn insecticides and provide an example of using genome editing to verify a target premature truncation associated with resistance.


Assuntos
Spodoptera , Animais , Sistemas CRISPR-Cas , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Resistência a Inseticidas , Inseticidas , Macrolídeos , Receptores Nicotínicos
17.
Int J Cardiovasc Imaging ; 36(2): 171-178, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31919705

RESUMO

Although drug-coated balloon (DCB) angioplasty is an effective therapy for drug-eluting stent- in stent restenosis (DES-ISR) after coronary stenting, recurrent ISR after DCB angioplasty still occurs. Different patterns of DES-ISR responding to DCB are largely unknown. This study sought to assess outcomes of different patterns of DES-ISR treated with DCB. From December 2014 to December 2016, a total of 160 DES-ISR lesions treated with DCB were retrospectively evaluated. Restenosis patterns were classified into two groups according to Mehran classification: focal, defined as < 10 mm, 58 lesions (36.3%); non-focal, which were diffuse, proliferative, or obstructive, 102 lesions (63.7%). The primary endpoint was binary restenosis rate at 9-month angiographic follow-up. Secondary endpoint was major adverse cardiac events (MACE) at 24-month follow-up. Baseline characteristics were comparable between the two groups. Angiographic follow-up rate was 93.7% (93.1% in the focal group and 94.1% in the non-focal group). The focal group had a lower recurrent restenosis rate compared to the non-focal group (3.7% vs. 33.3%, respectively; P = 0.003) at an average angiographic follow-up of 10 (10.4 ± 6.2) months. There was no difference in MACE between the two groups (6.9% vs. 11.8%, respectively; P = 0.70) at (22.7 ± 9.1) months clinical follow-up. On multivariate logistic regression analysis, focal pattern (OR 13.033; 95% CI 2.441-69.573, P = 0.003) and post-procedure DS% (OR 1.142; 95% CI 1.070-1.218, P = 0.000) were predictive factors of binary restenosis after DCB angioplasty. On multivariate analysis, focal pattern of ISR was a predictive factor of MACE (OR 0.260; 95% CI 0.071-0.959, P = 0.043), and diabetes mellitus (DM) was an independent predictor of MACE after DCB angioplasty (OR 5.045; 95% CI 1.179-21.590, P = 0.029). The present study suggests that DCB provides much better clinical, angiographic outcomes in patients with focal DES-ISR than non-focal DES-ISR.


Assuntos
Angioplastia Coronária com Balão/instrumentação , Cateteres Cardíacos , Materiais Revestidos Biocompatíveis , Reestenose Coronária/terapia , Stents Farmacológicos , Intervenção Coronária Percutânea/instrumentação , Idoso , Angioplastia Coronária com Balão/efeitos adversos , Angiografia Coronária , Reestenose Coronária/diagnóstico por imagem , Reestenose Coronária/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/efeitos adversos , Intervalo Livre de Progressão , Desenho de Prótese , Recidiva , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo
18.
AAPS PharmSciTech ; 21(2): 38, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31897797

RESUMO

In the study, we developed a novel oral dosage form of Compound Danshen to resolve the problems of low bioavailability, disequilibrium in drug release, and stomach degradation of active components of Compound Danshen in conventional formulas. A colon-specific osmotic pump capsule (COPC) of Compound Danshen was prepared using a semipermeable shell with the core components. Using a single-factor method, we obtained the optimal formulation that consisted of Salvia miltiorrhiza extract, Panax notoginseng extract, Borneol, sodium chloride, polyethylene oxide wsr-N10, hydroxypropyl-ß-cyclodextrin, and ludipress. Moreover, in vitro dissolution test showed simultaneous releases of active ingredients from Compound Danshen COPC over 12 h at pH 7.8, displaying zero-order release characteristics. The impetus of drug release mainly depended on the difference in osmotic pressure across the capsule shell. Next, scanning electron microscopy showed morphological changes in the capsule shell during the dissolution test. More importantly, pharmacokinetic study in beagle dogs indicated that relative bioavailability was 330.58% and retention time was greatly prolonged in Compound Danshen COPC, compared with those in marketed Compound Danshen tablet products. Finally, in vivo imaging studies in beagle dogs showed that COPC was stable in gastrointestinal tract and the drug was specifically released in the colon region. A colon-specific osmotic pump capsule (COPC) of Compound Danshen was developed and optimized to achieve simultaneous zero-order release of multiple active components of Compound Danshen in the colon. More importantly, the COPC have proved to improve the bioavailability and prolong the retention time of Compound Danshen, compared with those in a marketed product.


Assuntos
Formas de Dosagem , Medicamentos de Ervas Chinesas/administração & dosagem , Administração Oral , Animais , Disponibilidade Biológica , Canfanos/química , Colo/metabolismo , Preparações de Ação Retardada , Cães , Composição de Medicamentos , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacocinética , Excipientes , Pressão Osmótica , Panax notoginseng/química , Salvia miltiorrhiza/química , Solubilidade
19.
Insect Sci ; 27(4): 791-800, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31140744

RESUMO

Insect ryanodine receptors (RyRs) are the targets of diamide insecticides. Two point mutations G4946E and I4790M (numbering according to Plutella xylostella, PxRyR) in the transmembrane domain of the insect RyRs associated with diamide resistance have so far been identified in three lepidopteran pests, P. xylostella, Tuta absoluta and Chilo suppressalis. In this study, we identified one of the known RyR target site resistance mutations (I4790M) in a field-collected population of Spodoptera exigua. The field-collected WF population of S. exigua exhibited 154 fold resistance to chlorantraniliprole when compared with the susceptible WH-S strain. Sequencing the transmembrane domains of S. exigua RyR (SeRyR) revealed that the resistant WF strain was homozygous for the I4743M mutation (corresponding to I4790M in PxRyR), whereas the G4900E allele (corresponding to G4946E of PxRyR) was not detected. The 4743M allele was introgressed into the susceptible WH-S strain by crossing WF with WH-S, followed by three rounds of backcrossing with WH-S. The introgressed strain 4743M was homozygous for the mutant 4743M allele and shared about 94% of its genetic background with that of the recipient WH-S strain. Compared with WH-S, the near-isogenic 4743M strain showed moderate levels of resistance to chlorantraniliprole (21 fold), cyantraniliprole (25 fold) and flubendiamide (22 fold), suggesting that the I4743M mutation confers medium levels of resistance to all three diamides. Genetic analysis showed diamide resistance in the 4743M strain was inherited as an autosomal and recessive trait. Results from this study have direct implications for the design of appropriate resistance monitoring and management practices to sustainably control S. exigua.


Assuntos
Diamida/farmacologia , Proteínas de Insetos/genética , Resistência a Inseticidas/genética , Inseticidas/farmacologia , Canal de Liberação de Cálcio do Receptor de Rianodina/genética , Spodoptera/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , China , Proteínas de Insetos/química , Proteínas de Insetos/metabolismo , Larva/efeitos dos fármacos , Larva/genética , Larva/crescimento & desenvolvimento , Larva/fisiologia , Mutação , Canal de Liberação de Cálcio do Receptor de Rianodina/metabolismo , Alinhamento de Sequência , Spodoptera/efeitos dos fármacos , Spodoptera/crescimento & desenvolvimento , Spodoptera/fisiologia
20.
New Phytol ; 225(3): 1218-1233, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31560799

RESUMO

Increasing evidence indicates that DNA methylation is heritable and serves as an essential marker contributing to phenotypic variation. Linkage-linkage disequilibrium mapping was used to decipher the epigenetic architecture underlying nine growth and wood property traits in a linkage population (550 F1 progeny) and a natural population (435 unrelated individuals) of Populus using methylation-sensitive amplification polymorphism (MSAP)-based analysis. The interactions between genetic and epigenetic variants in the causative genes was further unveiled using expression quantitative trait methylation (eQTM) and nucleotide (eQTN) mapping strategies. A total of 163 epigenetic quantitative trait loci (epiQTLs; LOD ≥ 3.0), explaining 1.7-44.5% of phenotypic variations, were mapped to a high-resolution epigenetic map with 19 linkage groups, which was supported by the significant MSAP associations (P < 0.001) in the two populations. There were 23 causal genes involved in growth regulation and wood formation, whose markers were located in epiQTLs and associated with the same traits in both populations. Further eQTN and eQTM mapping showed that causal genetic and epigenetic variants within the 23 candidate genes may interact more in trans in gene expression and phenotype. The present study provides strategies for investigating epigenetic architecture and the interaction between genetic and epigenetic variants modulating complex traits in forest trees.

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