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1.
Sci Total Environ ; 732: 139127, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32438162

RESUMO

Two constructed wetland microbial fuel cell (CW-MFC) devices, experimental group (EG, with 5 mg/L Pb(II) addition) and control group (CG) were built to explore the changes in power generation, wastewater purification and microbial community structure under Pb(II) stress. The voltage of EG (343.16 ± 12.14 mV) was significantly higher (p < 0.01) than that of CG (295.49 ± 13.91 mV), and the highest power density of the EG and CG were 7.432 mW·m-2 and 3.873 mW·m-2, respectively. There was no significant difference in the removal of common pollutants between these groups except for the NH4+-N removal efficiency, which was probably caused by the inhibition of the bioactivity of Comamonas (AOB) in the anode of the experimental group by Pb(II). Pb(II) was effectively removed by CW-MFC (84.86 ± 3%), and the abundant amount of fulvic acid-like matter in the extracellular polymeric substance (EPS) of the EG contributed to its removal. The presence of Pb(II) had a negative effect on both microbial community diversity and species richness. The abundance of a lead resistance gene, pbrT, decreased with long-term Pb(II) pressure. This is evidence of microbial adaptation to Pb(II).

2.
BMC Cardiovasc Disord ; 20(1): 236, 2020 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-32429846

RESUMO

BACKGROUND: Takotsubo cardiomyopathy (TTC) has been widely recognized in recent decades and is triggered by either physical or psychological stressors. CASE PRESENTATION: A 70-year-old woman presented to the Emergency Department due to confusion, hypotension, fever, chills, and cough. She had a one-year history of diabetes insipidus. Pituitary function examination at admission revealed decreased thyroid, sex and adrenal hormones. Pituitary MRI displayed findings suggestive of nonhemorrhagic pituitary apoplexy. Electrocardiogram (ECG) revealed T-wave inversion and extended QT interval. Transthoracic echocardiogram (TTE) showed left ventricular apical dysplasia and ballooning, accompanied by reduced left ventricular ejection fraction. Coronary angiography (CAG) revealed no obvious coronary arterial stenosis. The left ventriculogram demonstrated an octopus clathrate appearance. Most ECG and TTE changes recovered 10 days later. CONCLUSIONS: To the best of our knowledge, this is the first report of newly diagnosed TTC associated with pituitary apoplexy.

3.
BMC Vet Res ; 16(1): 129, 2020 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-32381017

RESUMO

BACKGROUND: Recombinant Salmonella enterica serotype Choleraesuis (S. Choleraesuis) vaccine vector could be used to deliver heterologous antigens to prevent and control pig diseases. We have previously shown that a live-attenuated S. Choleraesuis vaccine candidate strain rSC0011 (ΔPcrp527::TT araC PBADcrp Δpmi-2426 ΔrelA199::araC PBADlacI TT ΔasdA33, Δ, deletion, TT, terminator) delivering SaoA, a conserved surface protein in most of S. suis serotypes, provided excellent protection against S. suis challenge, but occasionally lead to morbidity (enteritidis) in vaccinated mice (approximately 1 in every 10 mice). Thus, alternated attenuation method was sought to reduce the reactogenicity of strain rSC0011. Herein, we described another recombinant attenuated S. Choleraesuis vector, rSC0012 (ΔPfur88:: TT araC PBADfur Δpmi-2426 ΔrelA199:: araC PBADlacI TT ΔasdA33) with regulated delayed fur mutation to avoid inducing disease symptoms while exhibiting a high degree of immunogenicity. RESULTS: The strain rSC0012 strain with the ΔPfur88::TT araC PBADfur mutation induced less production of inflammatory cytokines than strain rSC0011 with the ΔPcrp527::TT araC PBADcrp mutation in mice. When delivering the same pS-SaoA plasmid, the intraperitoneal LD50 of rSC0012 was 18.2 times higher than that of rSC0011 in 3-week-old BALB/C mice. rSC0012 with either pS-SaoA or pYA3493 was cleared from spleen and liver tissues 7 days earlier than rSC0011 with same vectors after oral inoculation. The strain rSC0012 synthesizing SaoA induced high titers of anti-SaoA antibodies in both systemic (IgG in serum) and mucosal (IgA in vaginal washes) sites, as well as increased level of IL-4, the facilitator of Th2-type T cell immune response in mice. The recombinant vaccine rSC0012(pS-SaoA) conferred high percentage of protection against S. suis or S. Choleraesuis challenge in BALB/C mice. CONCLUSIONS: The live-attenuated Salmonella enterica serotype Choleraesuis vaccine rSC0012(pS-SaoA) with regulated delayed fur mutation provides a foundation for the development of a safe and effective vaccine against S. Choleraesuis and S. suis.

4.
BMJ Open Respir Res ; 7(1)2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32332025

RESUMO

BACKGROUND: A low-cost, quantitative method to evaluate sleep in the intensive care unit (ICU) that is both feasible for routine clinical practice and reliable does not yet exist. We characterised nocturnal ICU sleep using a commercially available activity tracker and evaluated agreement between tracker-derived sleep data and patient-perceived sleep quality. PATIENTS AND METHODS: A prospective cohort study was performed in a 40-bed ICU at a community teaching hospital. An activity tracker (Fitbit Charge 2) was applied for up to 7 ICU days in English-speaking adults with an anticipated ICU stay ≥2 days and without mechanical ventilation, sleep apnoea, delirium, continuous sedation, contact isolation or recent anaesthesia. The Richards-Campbell Sleep Questionnaire (RCSQ) was administered each morning by a trained investigator. RESULTS: Available activity tracker-derived data for each ICU study night (20:00-09:00) (total sleep time (TST), number of awakenings (#AW), and time spent light sleep, deep sleep and rapid eye movement (REM) sleep) were downloaded and analysed. Across the 232 evaluated nights (76 patients), TST and RCSQ data were available for 232 (100%), #AW data for 180 (78%) and sleep stage data for 73 (31%). Agreement between TST (349±168 min) and RCSQ Score was moderate and significant (r=0.34; 95% CI 0.18 to 0.48). Agreement between #AW (median (IQR), 4 (2-9)) and RCSQ Score was negative and non-significant (r=-0.01; 95% CI -0.19 to 0.14). Agreement between time (min) spent in light (259 (182 to 328)), deep (43±29), and REM (47 (28-72)) sleep and RCSQ Score was moderate but non-significant (light (r=0.44, 95% CI -0.05 to 0.36); deep sleep (r=0.44, 95% CI -0.11 to 0.15) and REM sleep (r=0.44; 95% CI -0.21 to 0.21)). CONCLUSIONS: A Fitbit Charge 2 when applied to non-intubated adults in an ICU consistently collects TST data but not #AW or sleep stage data at night. The TST moderately correlates with patient-perceived sleep quality; a correlation between either #AW or sleep stages and sleep quality was not found.

5.
ACS Nano ; 14(4): 4014-4026, 2020 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-32212674

RESUMO

Extracellular vesicles (EVs) released by mesenchymal stem cells (MSCs) have exhibited regenerative capability in animal models of ischemia-reperfusion (I/R) acute kidney injury (AKI) and are considered as potential alternatives to direct MSC therapy. However, real-time in vivo imaging of MSC-EVs in renal I/R injury has yet to be established. Renal intracellular targets of MSC-EVs responsible for their regenerative effects also remain elusive. Here, we report that we real-time observed MSC-EVs specifically accumulated in the injured kidney and were taken up by renal proximal tubular epithelia cells (TECs) via DPA-SCP with aggregation-induced emission (AIE) characteristics. DPA-SCP precisely tracked the fate of MSC-EVs in a renal I/R injury mouse model for 72 h and exhibited superior spatiotemporal resolution and tracking ability to popular commercially available EV tracker PKH26. Further analysis revealed that the accumulated MSC-EVs stimulated mitochondrial antioxidant defense and ATP production via activating the Keap1-Nrf2 signaling pathway, which protected TECs against oxidative insult by reducing mitochondrial fragmentation, normalizing mitochondrial membrane potential, and increasing mitochondrial DNA copy number. Increased microRNA-200a-3p expression in renal TECs induced by MSC-EVs was identified as a regulatory mechanism contributing to the protective actions on mitochondria as well as stimulating the renal signal transduction pathways. In conclusion, MSC-EVs accumulated in the renal tubules during renal I/R injury and promoted the recovery of kidney function via activating the Keap1-Nrf2 signaling pathway and enhancing mitochondrial function of TECs. DPA-SCP with AIE characteristics allows noninvasive and precise in vivo visualization of MSC-EVs in kidney repair.

6.
Zhen Ci Yan Jiu ; 45(3): 202-8, 2020 Mar 25.
Artigo em Chinês | MEDLINE | ID: mdl-32202711

RESUMO

OBJECTIVE: To explore the mechanism of electroacupuncture (EA) underlying improvement of cerebral infarction (CI) by investigating its influence on expression of cerebral Wnt7a, lymphoid enhancer factor-1 (LEF1), glycogen synthase kinase 3ß(GSK-3ß) and Dickkopf-1(DKK1) mRNA and proteins in CI rats. METHODS: A total of 280 male Wistar rats were randomly divided into blank control (n=10), sham-operation, model and EA groups,and 90 rats of the last 3 groups were further divided into 1, 3, 6, 9, 12 and 24 h, and 3, 7 and 12 d subgroups with 10 rats in each subgroup. The CI model was established by occlusion of the middle cerebral artery (MCAO). The sham-operation group received the same surgical operation but without thread embolus insertion. EA (2 Hz/15 Hz, 2 mA) was applied to "Shuigou" (GV26) for 20 min, once a day for 1, 3, 7 and 12 d, respectively. The neurological deficit was evaluated by using Neurological Severity Scores (NSS). The expression levels of Wnt7a,LEF1, GSK-3ß and DKK1 mRNAs and proteins in the right ischemic brain tissues were detected by Quantative real-time PCR and Western blot, respectively. RESULTS: After MCAO, the NSS score was significantly increased in the model and EA groups relevant to the blank control and sham-operation groups (P<0.01) and gradually decreased with the prolongation of ischemia time. After EA, the NSS scores were notably decreased on day 3, 7 and 12 in the EA group compared with the model group (P<0.05, P<0.01). After modeling, the expression levels of Wnt7a and LEF1 mRNAs from 3 h to 12 d, Wnt7a and LEF1 proteins from 6 h to 12 d were considerably increased (P<0.01, P<0.05), while those of GSK-3ß mRNA at 9, 12 and 24 h, GSK-3ß protein at 24 h and 3 d, and DKK1 mRNA at 24 h and 3 d and DKK1 protein at 3 d were obviously decreased in the model group relevant to the sham-operation group (P<0.05, P<0.01). After the intervention, the expression levels of Wnt7a mRNA at 12 h to 3 d, Wnt7α protein from 24 h to 12 d, LEF1 mRNA from 24 h to 12 d, and LEF1 protein from 3 d to 12 d were further apparently up-regulated (P<0.01, P<0.05), while those of GSK-3ß mRNA at 9 h, 3,7 and 12 d, and GSK-3ß protein at 12 h, 7 d and 12 d, and DKK1 mRNA at 12 h, 24 h and 3 d, and DKK1 protein at 24 h to 12 d were obviously down-regulated in the EA group relevant to the model group (P<0.01, P<0.05). No significant difference was found between the blank and sham-operation groups in the NSS scores and expression levels of Wnt7a, LEF1, GSK-3ß and DKK1 mRNAs and proteins at all the time points (P>0.05). CONCLUSION: EA of GV26 can significantly improve the neurological deficit symptoms in MCAO rats, which may be associated with its effects in up-regulating the expression of Wnt7a and LEF1 mRNAs and proteins, and in down-regulating the expression of GSK-3ß and DKK1 mRNAs and proteins.


Assuntos
Isquemia Encefálica , Eletroacupuntura , Animais , Encéfalo , Infarto Cerebral , Glicogênio Sintase Quinase 3 beta , Masculino , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Via de Sinalização Wnt
7.
Acta Physiol (Oxf) ; 229(2): e13438, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31900993

RESUMO

AIMS: Pathogenic variants of the SCN5A gene can cause Brugada syndrome (BrS) and long QT syndrome (LQTS), which predispose individuals to potentially fatal ventricular arrhythmias and sudden cardiac death. SCN5A encodes the NaV 1.5 protein, the pore forming α-subunit of the voltage-dependent cardiac Na+ channel. Using a WW domain, the E3 ubiquitin ligase Nedd4-2 binds to the PY-motif ([L/P]PxY) within the C-terminus of NaV 1.5, which results in decreased protein expression and current through NaV 1.5 ubiquitination. Here, we investigate the role of E3 ubiquitin ligase Nedd4-2-mediated NaV 1.5 degradation in the pathological mechanisms of the BrS-associated variant SCN5A-p.L1239P and LQTS-associated variant SCN5A-p.Y1977N. METHODS AND RESULTS: Using a combination of molecular biology, biochemical and electrophysiological approaches, we examined the expression, function and Nedd4-2 interactions of SCN5A-p.L1239P and SCN5A-p.Y1977N. SCN5A-p.L1239P is characterized as a loss-of-function, whereas SCN5A-p.Y1977N is a gain-of-function variant of the NaV 1.5 channel. Sequence alignment shows that BrS-associated SCN5A-p.L1239P has a new Nedd4-2-binding site (from LLxY to LPxY). This new Nedd4-2-binding site increases the interaction between NaV 1.5 and Nedd4-2, enhancing ubiquitination and degradation of the NaV 1.5 channel. Disruption of the new Nedd4-2-binding site of SCN5A-p.L1239P restores NaV 1.5 expression and function. However, the LQTS-associated SCN5A-p.Y1977N disrupts the usual Nedd4-2-binding site (from PPxY to PPxN). This decreases NaV 1.5-Nedd4-2 interaction, preventing ubiquitination and degradation of NaV 1.5 channels. CONCLUSIONS: Our data suggest that the PY-motif plays an essential role in modifying the expression/function of NaV 1.5 channels through Nedd4-2-mediated ubiquitination. Alterations of NaV 1.5-Nedd4-2 interaction represent a novel pathological mechanism for NaV 1.5 channel diseases caused by SCN5A variants.

8.
Int Heart J ; 60(6): 1415-1420, 2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31735781

RESUMO

Hypertrophic cardiomyopathy (HCM) is one of the most common inherited cardiovascular diseases and possesses a high risk for sudden cardiac death. Although mutations in more than 20 genes have been reported to be associated with HCM thus far, the genetic backgrounds of most HCM patients are not fully understood. We performed a genetic analysis in a Chinese family that presented with HCM using next-generation sequencing (NGS). Clinical data, family histories, and blood samples were collected from the proband and family members. Five patients showed typical clinical symptoms of HCM. One subject was the victim of sudden cardiac death. By NGS, we determined that these subjects with HCM symptoms carried a missense heterozygous genetic mutation c.2632C>A (p.V878L) in the myosin heavy chain 7 (MYH7) gene with an autosomal dominant pattern of inheritance. Individuals without this mutation showed no symptoms or cardiac structural abnormalities related to HCM. Bioinformatics evaluation predicted this mutant as "damaging" and "disease causing". Additionally, sequence alignment showed that this mutant is located in an evolutionarily conserved region of MYH7 in multiple species. Our results describe a potentially pathogenic mutation associated with HCM, which may extend the spectrum of HCM phenotypes related to MYH7 gene mutations.


Assuntos
Miosinas Cardíacas/genética , Cardiomiopatia Hipertrófica Familiar/genética , Morte Súbita Cardíaca/etiologia , Mutação de Sentido Incorreto/genética , Cadeias Pesadas de Miosina/genética , Adolescente , Adulto , Idoso , Cardiomiopatia Hipertrófica Familiar/diagnóstico , Feminino , Testes Genéticos , Humanos , Padrões de Herança/genética , Masculino , Pessoa de Meia-Idade , Linhagem , Adulto Jovem
9.
Zhen Ci Yan Jiu ; 44(10): 715-21, 2019 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-31657160

RESUMO

OBJECTIVE: To observe the change of neovascular morphology and angiogenesis related factors in the ischemic cerebral area after cerebral infarction and the intervention effect of electroacupuncture (EA). METHODS: Wistar rats were randomly divided into model group(n=90), EA group(n=90), sham operation group(n=90) and control group(n=10). The first three groups were further divided into 1 h, 3 h, 6 h, 9 h, 12 h, 24 h, 3 d, 7 d and 12 d subgroups(n=10 in each subgroup). The cerebral infarction model was established by middle cerebral artery occlusion(MCAO). EA(15 Hz, 2 mA) was applied to "Shuigou"(GV26) for 20 min in the EA group. The 1, 3, 6, 9, 12, 24 h subgroups were treated immediately after modeling, the 3, 7, 12 d subgroups were treated once daily for 3, 7 or 12 days. The neovascular endothelial cells were displayed by immunofluorescence double labeling staining. Quantitive real-time PCR and Western blot were applied to detect the changes of basic fibroblast growth factor (bFGF), angiogenin (Ang) -1, 2, platelet-derived growth factor b (PDGF-b) in ischemic brain tissue, respectively. RESULTS: After modeling, CD31 and Ki67 positive cells were first observed at 24 h in the model group, and reached the peak at 3 d, decreased at 7 d. While in the EA group, the CD31 and Ki67 positive cells were first observed at 12 h, and reached the peak at 3 d, and gradually decreased until 12 d. Compared with the control group, the mRNA expressions of bFGF at 9 h-12 h, Ang-1 at 12 h-12 d, Ang-2 at 1 h-12 d and PDGF-b at 1 h, 6 h, 9 h, 24 h-12 d were increased in the model group(P<0.01, P<0.05). After EA, the mRNA expressions of bFGF at 24 h-12 d, Ang-1 at 3 d-12 d, Ang-2 at 3 h-24 h and PDGF-b at 3 h, 6 h, 3 d-12 d were increased(P<0.05, P<0.01). In comparison with the control group, the proteins of bFGF at 24 h, Ang-1 at 6 h-12 d, Ang-2 at 1 h-12 d and PDGF-b at 1 h-7 d were increased in the model group(P<0.05, P<0.01). After EA, the proteins of bFGF at 3 d-12 d, Ang-1 at 3 d-12 d, Ang-2 at 3 h-12 h and PDGF-b at 6 h, 3 d-12 d were increased compared with the model group(P<0.05, P<0.01). CONCLUSION: EA can up-regulate the expression of angiogenesis-related factors in MCAO rats, which has an important role in the establishment of blood vessel regeneration and collateral circulation, and thus promote the recovery of neurological function.


Assuntos
Isquemia Encefálica , Eletroacupuntura , Indutores da Angiogênese , Animais , Encéfalo , Células Endoteliais , Neovascularização Patológica , Ratos , Ratos Wistar
10.
Hortic Res ; 6: 102, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31645957

RESUMO

WRKY transcription factors are involved in defense responses caused by biotic stresses. Phylloxera (Daktulosphaira vitifoliae Fitch), a pest widespread in viticulture, elicits transcriptional reprogramming of plant defense-associated components, such as regulons related to WRKYs and salicylic acid (SA) signaling. In this study, we characterized WRKY46, a WRKY transcription factor responsible for phylloxera attack, and revealed the molecular mechanism for WRKY-mediated defense responses to phylloxera. qRT-PCR and GUS staining analyses revealed that WRKY46 is induced in response to phylloxera damage and mechanical wounding. VvWRKY46 is a nuclear-localized transcription factor that activates its downstream target VvCHIB by direct protein-DNA interaction. Regulons involved in the SA-mediated defense response were regulated during incompatible interactions between "1103 Paulsen" rootstock and phylloxera. In addition, WRKY46 exhibited a higher transcript abundance in "1103 Paulsen" than in "Crimson Seedless", regardless of whether the plants were infected with phylloxera. Furthermore, the enhanced expression of VvWRKY46 significantly attenuated phylloxera attack and delayed nymph development of composite grape plants. In summary, we demonstrated that WRKY46 plays a role in the SA-mediated defense-regulatory network by directly binding to the downstream structural gene VvCHIB. The phylloxera-responsive gene WRKY46 was identified, which could improve the understanding of the basic mechanism of grapevine in response to phylloxera.

11.
Chimia (Aarau) ; 73(9): 698-706, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31514769

RESUMO

Heterogeneous catalysis has long been a workhorse for the chemical industry and will likely play a key role in the emerging area of renewable chemistry. However, renewable molecule streams pose unique challenges for heterogeneous catalysis due to their high oxygen content, frequent low volatility and the near constant presence of water. These constraints can often lead to the need for catalyst operation in harsh liquid phase conditions, which has compounded traditional catalyst deactivation issues. Oxygenated molecules are also frequently more reactive than petroleum-derived molecules, which creates a need for highly selective catalysts. Synthetic control over the nanostructured environment of catalytic active sites could facilitate the creation of both more stable and selective catalysts. In this review, we discuss the use of metal oxide deposition as an emerging strategy that can be used to synthesize and/or modify heterogeneous catalysts to introduce tailored nanostructures. Several important applications are reviewed, including the synthesis of high surface area mesoporous metal oxides, the enhancement of catalyst stability, and the improvement of catalyst selectivity.

12.
Sensors (Basel) ; 19(15)2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31374859

RESUMO

Real-time kinematic (RTK) positioning is a satellite navigation technique that is widely used to enhance the precision of position data obtained from global navigation satellite systems (GNSS). This technique can reduce or eliminate significant correlation errors via the enhancement of the base station observation data. However, observations received by the base station are often interrupted, delayed, and/or discontinuous, and in the absence of base station observation data the corresponding positioning accuracy of a rover declines rapidly. With the strategies proposed till date, the positioning accuracy can only be maintained at the centimeter-level for a short span of time, no more than three min. To address this, a novel asynchronous RTK method (that addresses asynchronous errors) that can bridge significant gaps in the observations at the base station is proposed. First, satellite clock and orbital errors are eliminated using the products of the final precise ephemeris during post-processing or the ultra-rapid precise ephemeris during real-time processing. Then the tropospheric error is corrected using the Saastamoinen model and the asynchronous ionospheric delay is corrected using the carrier phase measurements from the rover receiver. Finally, a straightforward first-degree polynomial function is used to predict the residual asynchronous error. Experimental results demonstrate that the proposed approach can achieve centimeter-level accuracy for as long as 15 min during interruptions in both real-time and post-processing scenarios, and that the accuracy of the real-time scheme can be maintained for 15 min even when a large systematic error is projected in the U direction.

13.
Phytomedicine ; 64: 152899, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31454649

RESUMO

BACKGROUND: P2Y12 receptor (P2Y12R) is a newly discovered Gi-coupled ADP receptor that plays critical role in platelet function. Ginsenosides are the main constituents responsible for most of pharmacological actions of ginseng, especially cardio-cerebrovascular protective efficacy that is closely related to the influence on platelet function. HYPOTHESIS/PURPOSE: To explore stereoselective effect of naturally abundant ginsenoside isomers, including the C-20 epimers of protopanaxadiol (PPD), protopanaxatriol (PPT), and their glycosides Rg2, Rg3, Rh1, Rh2 on P2Y12R in platelets. STUDY DESIGN/METHODS: Both in vitro assay and in silico molecular docking study were performed to investigate the stereoselective effects. RESULTS: In vitro assay using washed rat platelets revealed differential effects of ginsenoside isomers on ADP-induced platelet aggregation with the direction and degree of action varying with chemical structures. More to the point, the ginsenoside 20S-Rh2 but not its 20R-epimer was found to be the only one that could significantly promote in vitro platelets aggregation induced by ADP. The correlation analysis demonstrated that ginsenosides may have impact on P2Y12R related platelet functions through a cAMP-dependent pathway. Molecular docking stimulation further indicated that ginsenoside isomers could be potent substrate of P2Y12R with differential protein-ligand interaction that would be responsible for the stereoselective efficacy of C-20 ginsenoside epimers. Hydrogen bonding with Asp266 via the C-20 hydroxyl may provide ginsenosides with promoting effect on ADP-induced platelets aggregation, whereas interactions with Tyr105 could contribute to the promotion of inhibitory efficacy. CONCLUSION: Ginsenosides are potent P2Y12R substrate with stereoselective effects on P2Y12R-related platelet function, which result from their chemical diversity and are closely related to the different interaction ways as P2Y12R ligand.

14.
Zhongguo Zhong Yao Za Zhi ; 44(11): 2191-2196, 2019 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-31359641

RESUMO

Classical prescriptions are precious wealth left by ancient Chinese medical scientists. Moreover,they are also the important part of the treasure-house in Chinese medicine. Classical prescriptions have a long and rich history for human-use in China and play an important role in keeping people healthy. The state administration of traditional medicine of China published the Catalogue of Classical Prescriptions(first batch) in 2018. This measure has inspired the enthusiasm of Chinese medicine manufacturers to study ancient classical prescriptions and develop classical compound prescriptions. Based on the first batch of classical prescriptions, the dosage forms, sources, prescription components, decocting degree, use of toxic drugs and processing methods of classical prescriptions. The results showed that most of the classical prescriptions in the first batch were decoction and boiled powder,while only four of them were powder and paste forms,all of which were originated from representative classics in the past dynasties. The dosage and decocting degree of decoction were greater than those of boiled powder. The dosage and decocting degree of decoction in Han and Tang Dynasties was close to that in Ming and Qing Dynasties,higher than that in Song and Jin Dynasties. Moreover,the average number of herbs in the prescriptions in Han Dynasty was the smallest. The use of toxic traditional Chinese medicine was the most frequent in Han Dynasty, and Pinellia ternata was the most common toxic medicine. There were various processing methods, including cleansing, cutting, stir-frying, roasting and so on. In this paper, the dosage forms of traditional paste, the time concept of decoction in the ancient times, the traditional roasting method and the processing method of toxic drugs were summarized to provide ideas and reference for further development of classical prescriptions.


Assuntos
Medicamentos de Ervas Chinesas/normas , Medicina Tradicional Chinesa , China
15.
Cardiol Ther ; : 357-364, 2019 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-31124018

RESUMO

INTRODUCTION: Transcatheter aortic valve replacement (TAVR) has become a widely accepted treatment option for patients with severe aortic stenosis (AS) who are considered intermediate- and high-risk surgical candidates. The purpose of this study was to test the hypothesis that trans-apical TAVR would be associated with increased risk of new-onset intraventricular conduction delay (LBBB or RBBB). METHODS: We conducted a retrospective observational study of consecutive patients undergoing TAVR at a large, single institution. The incidence of new LBBB or RBBB was compared between femoral and apical TAVR patients. Multivariate analysis was performed to account for confounding variables, which included age, gender, CAD, PAD, hypertension, and diabetes. RESULTS: A total of 467 TAVR patients were included in the study, with 283 (60.6%) femoral approach and 184 (39.4%) apical approach. In univariate analysis, the apical approach (when compared to the femoral approach) was associated with a higher incidence of both new-onset LBBB (12.79 vs. 3.40%, p = 0.0002) and RBBB (5.49 vs. 0.81%, p = 0.0039). After controlling for potential confounding variables, the apical approach continued to be associated with a higher incidence of both new-onset LBBB (p = 0.0010) and RBBB (p = 0.0115). There was also a trend towards an association between diabetes and new-onset LBBB (p = 0.0513) in apical TAVR patients. In subgroup analysis, LBBB/RBBB occurring as a result of transapical TAVR was associated with more frequent hospitalizations > 30 days after TAVR, compared to transfemoral TAVR. Other post-procedural complications noted more frequently among patients undergoing transapical TAVR include arrhythmias including atrial fibrillation, peri-procedural myocardial infarction (within 72 h), mortality from unknown cause, and mortality from non-cardiac cause. CONCLUSIONS: Relative to transfemoral TAVR, patients undergoing transapical TAVR are at increased risk for new-onset bundle branch block, peri-procedural myocardial infarction, rehospitalization, TAV-in-TAV deployment, and all-cause mortality at 1 year. Interventional cardiologists and cardiothoracic surgeons alike should take these findings into consideration when choosing which approach is most suitable for patients undergoing TAVR for severe aortic stenosis.

16.
J Cancer Res Ther ; 15(2): 380-385, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30964115

RESUMO

Background: The value of saturation prostate biopsy (SPBx) in patients without biopsy history remains controversial. Materials and Methods: A total of 644 consecutive suspected prostate cancer (PCa) cases without biopsy history were retrospectively grouped as 24-core transperineal SPBx (n = 368) guided by coaxial needle and prostate transperineal biopsy (PBx) (systematic 14-core scheme, n = 276). PCa detection rates were compared based on prostate-specific antigen (PSA) levels, PSA density (PSAD), and Gleason scores. Complications associated with those procedures were assessed. Results: Coaxial SPBx was superior to the 14-core scheme for overall PCa detection rates (39.67% vs. 24.64%), at PSA levels of 4.1-10.0 ng/ml (37.37% vs. 23.48%) or 10.1-20.0 ng/ml (43.31% vs. 27.21%), and PSAD <0.15 (47.80% vs. 29.23%) or 0.15-0.24 (34.07% vs. 20.93%) (all P < 0.05). In patients with positive biopsy, the rates of nonclinically significant PCa were comparable between the two biopsy groups. Conclusions: Transperineal coaxial needle SPBx as the initial scheme improves PCa detection compared with initial systematic 14-core PBx, without increasing complications and overdiagnosis.


Assuntos
Biópsia com Agulha de Grande Calibre , Neoplasias da Próstata/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais , Biópsia com Agulha de Grande Calibre/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/terapia , Carga Tumoral
17.
Front Pharmacol ; 10: 280, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30967782

RESUMO

Rheumatoid arthritis (RA) is characterized by chronic progressive symmetrical synovitis and destruction of multiple joints. Glucocorticoids (GCs) are widely used in the treatment of RA. However, their adverse effects can be serious. Escin, which is isolated from Aesculus hippocastanum L., has been reported to have anti-inflammatory effects. We investigated the anti-RA effect of Escin combined with low dose GCs (dexamethasone, Dex) and the underlying mechanism. Adjuvant-induced RA rats and lipopolysaccharides (LPS)-injured RAW264.7 cells were used to investigate the anti-RA effects of Escin combined with low dose Dex in vivo and in vitro. The results showed that Escin combined with low-dose Dex significantly decreased arthritic index, serum IL-6 and TNF-α levels, reduced paw swelling, and ameliorated the joint pathology and immune organ pathology. Gene chip results revealed that Nr3c1 (GR) expression was significantly altered, and that GR was activated by Escin and low dose Dex in vivo and in vitro. Additionally, Escin combined with low dose Dex also significantly increased GR mRNA expression. However, when GR expression was suppressed by its specific inhibitor, the anti-RA effect of Escin combined with low-dose Dex was abolished. The data in this study demonstrated that Escin combined with Dex reduced the dose of Dex, and exerted significant anti-RA effects, which could also reduce the adverse effects of Dex. This combination might result from GR activation. This study might provide a new combination of drugs for the treatment of RA.

18.
Zhongguo Zhen Jiu ; 39(3): 323-8, 2019 Mar 12.
Artigo em Chinês | MEDLINE | ID: mdl-30942023

RESUMO

OBJECTIVE: To select the optimized treatment plan of acupuncture for lateral femoral cutaneous neuritis by using multiple indexes decision-making method based on the clinical evidence. METHODS: The randomized control trials (RCTs) regarding acupuncture for lateral femoral cutaneous neuritis in the CNKI database, CBM database, WANFANG database, VIP database, PubMed, Cochrane Library and Embase published before December 31, 2017 were comprehensively collected. The modified Jadad scale was used to evaluate the quality of the RCTs. Then the evaluation indexes were selected and the dimensions of evaluation indexes were standardized by using extreme difference transformation method. The weight of each index was determined by using relative comparison method and the standardized matrix was weighted. Thus, the ideal solution and the negative ideal solution were obtained, and the relatively degree of each treatment plan to the ideal solution was calculated to propose the optimized plan of acupuncture for lateral femoral cutaneous neuritis. RESULTS: A total of 18 RCTs were included, the optimized plan of acupuncture for lateral femoral cutaneous neuritis was using thin fire needle to rapidly prick the abnormal skin region with fast needle insertion-withdrawal technique; the fire needle was applied repeatedly; intensive pricking to form a treatment area; the treatment was given once every 5 days. CONCLUSION: Based on the current clinical evidence, the optimized plan of acupuncture for lateral femoral cutaneous neuritis is using thin fire needle to prick the abnormal skin region; the multiple methods of plum-blossom needling met the characteristic of lateral femoral cutaneous neuritis and is suitable for clinical selection. The main acupoints are ashi points in the abnormal skin area or the acupoints in the foot-yangming meridian and foot-shaoyang meridian, combined with lumbar Jiaji (EX-B2) points.


Assuntos
Terapia por Acupuntura , Meridianos , Neurite (Inflamação) , Humanos , Agulhas , Neurite (Inflamação)/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto
19.
Mol Pharmacol ; 96(1): 1-12, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31015282

RESUMO

The human ether-à-go-go-related gene (hERG) encodes the channel that conducts the rapidly activating delayed rectifier potassium current (IKr) in the heart. Reduction in IKr causes long QT syndrome, which can lead to fatal arrhythmias triggered by stress. One potential link between stress and hERG function is protein kinase C (PKC) activation; however, seemingly conflicting results regarding PKC regulation of hERG have been reported. We investigated the effects of PKC activation using phorbol 12-myristate 13-acetate (PMA) on hERG channels expressed in human embryonic kidney cell line 293 (HEK293) cells and IKr in isolated neonatal rat ventricular myocytes. Acute activation of PKC by PMA (30 nM, 30 minutes) reduced both hERG current (IhERG) and IKr Chronic activation of PKC by PMA (30 nM, 16 hours) increased IKr in cardiomyocytes and the expression level of hERG proteins; however, chronic (30 nM, 16 hours) PMA treatment decreased IhERG, which became larger than untreated control IhERG after PMA removal for 4 hours. Deletion of amino acid residues 2-354 (Δ2-354 hERG) or 1-136 of the N terminus (ΔN 136 hERG) abolished acute PMA (30 nM, 30 minutes)-mediated IhERG reduction. In contrast to wild-type hERG channels, chronic activation of PKC by PMA (30 nM, 16 hours) increased both Δ2-354 hERG and ΔN136 hERG expression levels and currents. The increase in hERG protein was associated with PKC-induced phosphorylation (inhibition) of Nedd4-2, an E3 ubiquitin ligase that mediates hERG degradation. We conclude that PKC regulates hERG in a balanced manner, increasing expression through inhibiting Nedd4-2 while decreasing current through targeting a site(s) within the N terminus.


Assuntos
Canal de Potássio ERG1/genética , Canal de Potássio ERG1/metabolismo , Miócitos Cardíacos/metabolismo , Proteína Quinase C/metabolismo , Acetato de Tetradecanoilforbol/farmacologia , Animais , Animais Recém-Nascidos , Células Cultivadas , Canal de Potássio ERG1/química , Ativação Enzimática/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Células HEK293 , Humanos , Miócitos Cardíacos/efeitos dos fármacos , Ubiquitina-Proteína Ligases Nedd4/metabolismo , Fosforilação , Proteólise , Deleção de Sequência
20.
Int J Pharm ; 560: 126-135, 2019 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-30742982

RESUMO

Afatinib, a selective and irreversible inhibitor of tyrosine kinase, was approved for the treatment of advanced non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) overexpression in 2013. Cetuximab (CTX), an anti-EGFR monoclonal antibody, is co-administered with afatinib to improve efficacy. Unfortunately, dose-related adverse reactions caused by combination therapy have affected patient compliance, and have resulted in treatment discontinuation in severe cases. In the present study, afatinib was encapsulated in "liposomes" (LPs) to achieve longer circulation in the blood and an enhanced permeability-and-retention effect in tumors. Concomitantly, CTX was designed to bind to drug-loaded LPs to form "immuno-LPs" for tumor-cell selectivity and therapeutic activity. In vitro, the cellular internalization rate of immuno-LPs was significantly higher than that of LPs (p < 0.05). In vivo, a markedly increased area under the curve and prolonged terminal half-life were detected in rats injected with the two LP formulations, indicating that LP encapsulation protected afatinib from binding to hemoglobin to control the risk of idiosyncratic drug reactions. Compared with free afatinib and LPs, immuno-LPs exhibited strongly enhanced drug delivery and antitumor efficacy in an NSCLC xenograft model, with stronger tumor selectivity and potentially fewer side-effects. Hence, EGFR-targeting immuno-LPs appear to be promising for NSCLC treatment.


Assuntos
Afatinib/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cetuximab/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , Células A549 , Afatinib/farmacocinética , Afatinib/farmacologia , Animais , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/farmacocinética , Antineoplásicos Imunológicos/farmacologia , Área Sob a Curva , Linhagem Celular Tumoral , Cetuximab/farmacologia , Sistemas de Liberação de Medicamentos , Receptores ErbB/metabolismo , Meia-Vida , Humanos , Lipossomos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Ratos , Ratos Sprague-Dawley , Ensaios Antitumorais Modelo de Xenoenxerto
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