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Phytochemical investigation on the ethanol extract of a well-known medicinal herb Leonurus japonicus, led to the separation of 18 labdane type diterpenoids (1-18). Through comprehensive spectroscopic analyses and quantum chemical calculations, these compounds were structurally characterized as six new interesting 5,5,5-di-spirocyclic ones (1-6), two new (7 and 8) and six known (13-18) interesting 6,5,5-di-spirocyclic ones, a new rare 14,15-dinor derivative (9), and three new ones incorporating a γ-lactone unit (10-12). An in vitro neuroprotective assay in RSC96 cells revealed that compounds 7 and 12 exhibited neuroprotective activity in a concentration-dependent way, comparable to the reference drug N-acetylcysteine.
Subject(s)
Magnetic Resonance Spectroscopy , Leonurus/chemistry , Plants, Medicinal , Diterpenes/chemistry , Plant Components, Aerial , Molecular StructureABSTRACT
Objective To evaluate the in vitro synergistic antifungal activity of HDAC inhibitors in combination with azole drugs against azoles-resistant Candida strains. Methods The checkerboard microdilution method was used to evaluate the antifungal activity of the HDAC inhibitors in combination with azole drugs against clinically drug-resistant strains. The fungistatic activity and toxicity of Rocilinostat was determined through time-growth curve assay and cytotoxicity assay. Results The compound Rocilinostat combined with azole drugs showed excellent synergistic antifungal activity against a variety of azoles-resistant Candida albicans and Candida glabrata. The combination of high concentration Rocilinostat with FLC exhibited fungistatic effects. Very low toxicity was detected with Rocilinostat towards normal cells. Rocilinostat showed better HDAC inhibitory activity than SAHA. Conclusion As a fungi HDAC inhibitor, Rocilinostat has excellent in vitro synergistic antifungal activity and no severe toxicity to normal human cells.
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Alcoholic dementia is increasingly becoming both a severe medical issue and a social problem;the unknown overall mecha-nism is the bottleneck for effective intervention and treatment of alcoholic brain injury. As the primary structure for the release, transmission of neurotransmitter and information integration between neurons, synapse plays a significant role in performing the advanced function of brain, such as learning and memory. Based on the neurobiological principles of synaptic structure and function, the changes in process and efficiency of synaptic transmission and information integration stressed by alcoholic molecular were reviewed in comparison with the nor-mal process. The molecular mechanisms for alcoholic brain damage in learning and memory abilities were systematically discussed from the levels of synaptic morphology, material components, and signal transduction, respectively, and the repairing strategies for the damaged syn-aptic structure were proposed accordingly. Hopefully, this review could provide a deep insight into understanding the molecular mechanism of alcoholic brain damage, and draw ideas for the memory-enhancing peptides development.
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Objective To study the changes in interleukin-32 (IL-32) in rats with Klebsiella bacillus pneumonia and approach its significance. Methods Seventy-two Sprague-Dawley(SD)rats were divide into control group,model group and experimental group by the method of random digits table,then the experimental group was subdivided into 4 hours and 1,3 and 5 days experimental subgroups(each n=6). The rat model of Klebsiella bacillus pneumonia was established by injection of 0.3 mL Klebsiella bacterial suspension into the trachea. Before the establishment of the model in the experimental group,IL-32 inhibitory agent,protease activated receptor-2(PAR2) was injected into the abdominal cavity. After model establishment,at different time points,blood was collected via tail vein to observe the changes in serum levels of IL-32,tumor necrosis factor-α(TNF-α),IL-6 and IL-8 in all the groups. The lungs were removed and stained with hematoxylin-eosin(HE)method to investigate the histopathological changes of the lung tissues under the light microscope. Results Compared to the control group, with the prolongation of time the levels of IL-32,TNF-α,IL-8 and IL-6 were increased gradually in the model group,and reached their peaks at 3 days〔IL-32(ng/L):84.40±28.24 vs. 18.57±3.86,t=5.544,P=0.002;TNF-α(ng/L):79.27±14.64 vs. 17.82±3.86, t=9.994, P=0.000;IL-8(ng/L):55.85±10.90 vs. 16.66±3.76,t=8.544, P=0.000;IL-6(ng/L):56.65±2.57 vs. 28.48±2.11,t=19.693,P=0.000〕;PAR2 could inhibit above indexes significantly,there was statistical difference at 3 days compared with the model group〔IL-32(ng/L):54.13±6.68 vs. 84.40±28.24,t=2.560,P=0.046;TNF-α(ng/L):49.12±3.56 vs. 79.27±14.64,t=4.901,P=0.003;IL-8 (ng/L):22.95±2.52 vs. 55.85±10.90,t=7.204,P=0.000;IL-6(ng/L):36.49±2.63 vs. 56.65±2.57,t=13.443, P=0.000〕. Under the light microscope,the inflammatory changes in the lung tissue in experimental group were milder than those in the model group. Conclusion As a pro-inflammatory cytokine,IL-32 can induce the production of TNF-α,IL-6 and IL-8,and the inhibition of IL-32 production may play a role in suppression of the development of Klebsiella bacillus pneumonia.
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Objective To investigate the relationships between the level of heat shock protein (HSPs) 70 and severity of sepsis in order to find its effects on the status of sepsis and the prognosis of the patients. Methods In total, 120 patients diagnosed to be suffering from sepsis from the emergency department were selected as studying subjects. According to SAPS Ⅱ score, all of these patients were divided into mild, moderate and severe groups (n =40 in each group) , and at the same time, 40 healthy volunteers were studied as controls. The levels of intracellular HSPs70 in peripheral blood neutrophil cells in the mild, moderate and severe groups were determined by using flow cytometry, while serum levels of procalcitonin (PCT) and C-reactive protein ( CRP) were measured as well. Results ① The levels of heat shock proteins HSPs70 in neutrophil cells and PCT in patients with sepsis escalated gradually with the increase in SAPS Ⅱ score, and there were significant different among the mild, moderate, and severe sepsis groups(P<0.05). ② In all septic patients, the death happened only in the severe group. Compared other markers in the survivals , the level of heat shock protein HSPs70 was significantly higher in fatal patients. ③ In curve plot analysis in the patients with sepsis done by the curve of receiver operating characteristic (ROC) , the area of HSPs70 in neutrophil cells under the curve was significantly larger as compared with that of PCT and CRP. Conclusions Heat shock protein HSPs70 has a certain clinical value in determining the severity of disease and prognosis of patients suffering from sepsis.
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Objective:To investigate the understanding of cancer pain by medical doctors and its therapeutic status in Shanghai. Methods:We recruited 1 982 medical physicians from 106 secondary and tertiary hospitals in Shanghai city from January to March in 2007. The understanding and the therapeutic status of cancer pain were investigated by conducting a questionnaire survey and the results were statistically analyzed.Rusults:There were 52.3% physicians who believed that they understand the treatment protocol of the Three-step Analgesic Ladder regimen. The rate increased by 21.6 percentage point compared with the results in 1999. The understanding degree of oncologists was significantly better than non-oncologists. There were 16.8% physicians giving the correct answers on the three main principles of the dosage titration in analgesic management. The correct rate of oncologists was significantly higher than that of non-oncologists. Opium with strong analgesic effect had become the first choice for severe cancer pain, and the use of pethidine (Dolantin) for severe cancer pain decreased significantly.The pain was significantly relieved in 74.8% patients. The pain-relieving rate increased by 25.4 percentage point compared with the results in 1999. There were 81.1% medical doctors confirming the effect of pain treatment and among them oncologists were more optimistic to therapeutic outcome than others. There were 93.3% physicians who agreed that it was necessary to carry out the standardized training of cancer pain treatment and the requirement of non-oncologists were much emergent. The over-strict controls by the hospitals and the regulations were the main obstacles for using analgesic drugs.Conclusion:The understanding of medical doctors and the diagnostic and therapeutic levels of cancer pain were improved significantly compared with those in 1999. But more training of cancer pain treatment are still required to publicize the standardized therapy and overcome the obstacles of using analgesic drug.