THINK - intensification of blood pressure lowering Therapeutics based on diuretics versus usual management for uncontrolled Hypertension IN patients with moderate to severe chronic Kidney disease: an open label, cluster randomized controlled, phase 3 trial - DR210320
Safety and Efficacy of Extracorporeal Cytokine Hemoadsorption in Septic Shock in Critically Ill Cirrhotics -A Prospective Randomized Controlled Trial
Patients with septic shock would be screened. Following this, patients meeting the inclusion and exclusion criteria will be screened and randomized to the two treatment groups. Standard criteria will be considered to define refractoriness to fluids. In all patients, baseline endotoxin activity assay and blood and urine sample will be stored for looking at the effect of therapy on these factors. Septic shock would be defined as clinical construct of sepsis with persisting hypotension requiring vasopressors to maintain MAP>=65 mm of Hg and having a serum lactate >2 mmol/L despite adequate volume resuscitation. Patients assigned to the treatment arm and who do not already have access for dialysis will have a standard hemodialysis catheter inserted in one of the femoral veins by the physician. Hemoperfusion will be carried out for one session within 12 hours for all randomized patient using the adsorption columns for Jianfan Biotechnology Co., Zhuhai, China). The hemoperfusion apparatus will be connected in front of the hemodialyzer in series. The procedure would be done for 2 hours without use of heparin with use of normal saline for pipeline flushing. In patients who also require hemodialysis the dialysis would subsequently be continued. Subsequent sessions of therapy would be done for patients (if required).
Anti-Ovarian Cancer Conotoxins Identified from Conus Venom.
作者: Shuang Ju ; Yu Zhang ; Xijun Guo ; Qinghui Yan ; Siyi Liu ; Bokai Ma ; Mei Zhang ; Jiaolin Bao ; Sulan Luo ; Ying Fu
Conotoxins constitute a treasury of drug resources and have attracted widespread attention. In order to explore biological candidates from the marine cone snail, we isolated and identified three novel conopeptides named as Vi14b, Vi002, Vi003, three conotoxin variants named as Mr3d.1, Mr3e.1, Tx3a.1, and three known conotoxins (Vi15a, Mr3.8 and TCP) from crude venoms of Conus virgo, Conus marmoreus and Conus texile. Mr3.8 (I-V, II-VI, III-IV) and Tx3a.1 (I-III, II-VI, IV-V) both showed a novel pattern of disulfide connectivity, different from that previously established for the µ- and ψ-conotoxins. Concerning the effect on voltage-gated sodium channels, Mr3e.1, Mr3.8, Tx3a.1, TCP inhibited Nav1.4 or Nav1.8 by 21.51~24.32% of currents at semi-activated state (TP2) at 10 μmol/L. Certain anti-ovarian cancer effects on ID-8 cells were exhibited by Tx3a.1, Mr3e.1 and Vi14b with IC50 values of 24.29 µM, 54.97 µM and 111.6 µM, respectively. This work highlights the role of conotoxin libraries in subsequent drug discovery for ovarian cancer treatment.
2022-10-03·Molecules (Basel, Switzerland)
Synthesis and Antifungal Activity of New butenolide Containing Methoxyacrylate Scaffold.
作者: Qian Zhang ; Yihao Li ; Bin Zhao ; Leichuan Xu ; Haoyun Ma ; Mingan Wang
In order to improve the antifungal activity of new butenolides containing oxime ether moiety, a series of new butenolide compounds containing methoxyacrylate scaffold were designed and synthesized, based on the previous reports. Their structures were characterized by 1H NMR, 13C NMR, HR-MS spectra, and X-ray diffraction analysis. The in vitro antifungal activities were evaluated by the mycelium growth rate method. The results showed that the inhibitory activities of these new compounds against Sclerotinia sclerotiorum were significantly improved, in comparison with that of the lead compound 3-8; the EC50 values of V-6 and VI-7 against S. sclerotiorum were 1.51 and 1.81 mg/L, nearly seven times that of 3-8 (EC50 10.62 mg/L). Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) observation indicated that compound VI-3 had a significant impact on the structure and function of the hyphal cell of S. sclerotiorum mycelium and the positive control trifloxystrobin. Molecular simulation docking results indicated that the introduction of methoxyacrylate scaffold is beneficial to improving the antifungal activity of these compounds against S. sclerotiorum, which can be used as the lead for further structure optimization.
2019-09-04·Scientific reports3区 · 综合性期刊
Target-oriented motor imagery for grasping action: different characteristics of brain activation between kinesthetic and visual imagery.
3区 · 综合性期刊
作者: Woo Hyung Lee ; Eunkyung Kim ; Han Gil Seo ; Byung-Mo Oh ; Hyung Seok Nam ; Yoon Jae Kim ; Hyun Haeng Lee ; Min-Gu Kang ; Sungwan Kim ; Moon Suk Bang
Motor imagery (MI) for target-oriented movements, which is a basis for functional activities of daily living, can be more appropriate than non-target-oriented MI as tasks to promote motor recovery or brain-computer interface (BCI) applications. This study aimed to explore different characteristics of brain activation among target-oriented kinesthetic imagery (KI) and visual imagery (VI) in the first-person (VI-1) and third-person (VI-3) perspectives. Eighteen healthy volunteers were evaluated for MI ability, trained for the three types of target-oriented MIs, and scanned using 3 T functional magnetic resonance imaging (fMRI) under MI and perceptual control conditions, presented in a block design. Post-experimental questionnaires were administered after fMRI. Common brain regions activated during the three types of MI were the left premotor area and inferior parietal lobule, irrespective of the MI modalities or perspectives. Contrast analyses showed significantly increased brain activation only in the contrast of KI versus VI-1 and KI versus VI-3 for considerably extensive brain regions, including the supplementary motor area and insula. Neural activity in the orbitofrontal cortex and cerebellum during VI-1 and KI was significantly correlated with MI ability measured by mental chronometry and a self-reported questionnaire, respectively. These results can provide a basis in developing MI-based protocols for neurorehabilitation to improve motor recovery and BCI training in severely paralyzed individuals.