A Series of Novel HDAC Inhibitors with Anthraquinone as a Cap Group.

Although anthraquinone derivatives possess significant antitumor activity, most of them also displayed those side effects like cardiotoxicity, mainly owing to their inhibition of topoisomerase II of DNA repair mechanisms. Our raised design strategy by switching therapeutic target from topoisomerase II to histone deacetylase (HDAC) has been applied to the design of anthraquinone derivatives in current study. Consequently, a series of novel HDAC inhibitors with a tricylic diketone of anthraquinone as a cap group have been synthesized. After screening and evaluation, compounds 4b, 4d, 7b and 7d have displayed the comparable inhibition in enzymatic activity and cell proliferation than that of Vorinostat (SAHA). Notably, compound 4b showed certain selectivity of antiproliferative effects on cancer cell lines over non-cancer cell lines.

Serum levels of interleukin-1 beta, interleukin-6 and melatonin over summer and winter in kidney deficiency syndrome in Bizheng rats.

OBJECTIVE: To observe the seasonal changes in serum levels of interleukin-1 beta (IL-1ß), interleukin-6 (IL-6) and melatonin (MT) in Bizheng rat model, and explore the relationship between MT and the pathogenesis of rheumatoid arthritis. METHODS: One hundred and sixty Sprague-Dawley rats were randomly divided into four groups in summer (n=80) and winter (n=80) respectively: normal group, collagen-induced arthritis (CIA) model group, operation group, and sham-operation group (n=20 in each group). The CIA model group was injected with collagen emulsion at the base of the tail to induce arthritis. The rats in the operation group received pineal gland resection, and 7 days after the first operation, underwent testectomy or oophorectomy. The rats in the sham-operation group were operated to ligature the sagittal sinus, without extracting the pineal gland. After the operations, the operation group and the sham-operation group both were immunized as the CIA group was. The serum levels of IL-1ß, IL-6 and MT in different groups were measured by radioimmunoassay. RESULTS: Compared with the normal group, the serum levels of IL-1ß and IL-6 increased in the CIA model, operation, and sham-operation groups both in summer and in winter (IL-1ß in summer, P=0.008, P<0.01, P=0.012; IL-1ß in winter, P=0.019, P<0.01, P=0.027; IL-6 in summer, P=0.028, P<0.01, P=0.024; IL-6 in winter, P=0.006, P<0.01, P=0.008). In the operation group, the serum levels of IL-1ß and IL-6 in winter were higher than in summer, but with no statistically significant differences (P=0.844, 0.679). Compared with the normal group, the serum level of MT significantly increased in summer and winter in both the CIA model group (P=0.002, 0.008) and the sham-operation group (P=0.003, 0.007), while significantly decreased in the operation group (P=0.023, 0.003). There was no significant difference in MT level in the operation group between summer and winter (P=0.947). CONCLUSIONS: The increase of serum levels of IL-1ß and IL-6 may exacerbate the inflammatory reaction and cause a more severe condition in the rheumatoid arthritis. The concentrations of IL-1ß, IL-6, and MT correspond with the change of seasons, confirming that there are connections between nature and human body.

Creation of four-mode weighted cluster states with atomic ensembles in high-Q ring cavities.

Two schemes for the preparation of weighted continuous variable cluster states with four atomic ensembles are proposed. In the first scheme, the four separated atomic ensembles inside a two-mode ring cavity are driven by pulse laser fields. The basic idea of the scheme is to transfer the ensemble bosonic modes into suitable linear combinations that can be prepared in a pure cluster state by a sequential application of the laser pulses with the aid of the cavity dissipation. In the second one, we take two separate two-mode cavities, each containing two atomic ensembles. The distant cavities are coupled by dissipation in a cascade way. It has been found that the mixed cluster state can be produced. These schemes may contribute towards implementing continuous variable quantum computation, quantum communication and networking based on atomic ensembles.

Laboratory evaluation of the molluscicidal activity of Pulsatilla chinensis (Bunge) Regel saponins against the snail Oncomelania hupensis.

OBJECTIVE: To observe the toxicity of Pulsatilla chinensis (Bunge) Regel saponins (PRS) against Oncomelania hupensis (O. hupensis). METHODS: O. hupensis snails were exposed to 40% and 80% of 24 h LC50 of PRS for 24 h, and then choline esterase (CHE), alanine aminotransferase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) activities in cephalopodium and liver of snails were determined. Niclosamide (NIC) was used as the reference molluscicide. Zebra fish lethality test was evaluated to non-target aquatic species of PRS. RESULTS: The molluscicidal activity of PRS (LC50 at 24 h: 0.48 mg/L) was similar to that of NIC (LC50 at 24 h: 0.16 mg/L). Significant alterations about CHE, ALP, and ALT activities both in the cephalopodium and the liver of snails were observed when O. hupensis was exposed to 40% and 80% LC50 of PRS or NIC for 24 h. PRS and NIC could not affect LDH activity in the cephalopodium and the liver. Lower toxicity to fish of PRS was observed up to the highest concentration tested than NIC. CONCLUSION: PRS, as compared with the reference molluscicide NIC, is thought to be used for the control of harmful vector snails safely.

In vitro evaluation of schistosomicidal potential of curcumin against Schistosoma japonicum.

Curcumin is a polyphenol derived from the dietary spice turmeric. The aim of this study was to investigate the in vitro effect of curcumin against eggs, cercariae, pre-adults, and adults of Schistosoma japonicum compared to praziquantel. After incubated by different concentration of curcumin or praziquantel in different time, the percent hatching rates of eggs, the percent dead rates of cercariae, and the number of dead worms were observed. Curcumin showed time- and dose-dependent schistosomicidal effects on every life stages of S. japonicum. In addition, curcumin exhibited an optimal activity against the adult stage with no differential sensitivity between male and female worms and decreased motor activity of these worms without tegumental alterations. The promising in vitro effects on all stages of S. japonicum warrants further evaluation for the prophylactic and therapeutic values in the early and late schistosomiasis in field trials.

[Clinical study of selective multifetal pregnancy reduction in second trimester].

OBJECTIVE: To investigate the operative indication, timing, method, selective standards of feticided fetus and the number of reduced fetuses of selective multifetal pregnancy reduction in second trimester, and the pregnancy outcome of multifetal pregnancy by this operation. METHODS: Trans-abdominal selective multifetal pregnancy reductions in 37 cases of multiple pregnancy (twins 6 cases, triplets 21 cases, quadruplets 8 cases, and quintuplets 2 cases) during 12(+1) - 25 weeks were performed under ultrasound guidance. The fetus to be reduced was injected potassium chloride (KCl) intracardiacally until the fetal heartbeat stopped gradually. Totally 46 fetuses were reduced. Periodic prenatal examination and monitoring of coagulation function were carried out after the procedure. The pregnancy complications and pregnancy outcome of all cases were recorded. RESULTS: (1) The successful ratio of reduction was 100% (46/46 fetuses) and the successful pregnancy ratio was 88.9% (24/27). (2)Among all the 37 cases, fifteen delivered after 36 weeks, seven delivered in 32 - 36 weeks, three delivered in 28 - 32 weeks, two aborted after feticide, and ten cases were in pregnancy at the time of this study. The mean gestational age of all was (34.9 +/- 4.1) weeks, and the delivery ratio after 28 weeks was 92.6% (25/27). (3) The mean birth weight of singletons was (3014 +/- 640) g, and of twins was (2557 +/- 573) g. The neonates of three triplets all died except for in one case two fetuses were alive. (4) Except in two cases after reducing one fetus of monoamniotic twins, another one died within 24 hours, the remaining fetuses were all alive. (5) Pre-eclampsia occurred in three cases. None of the cases had blood coagulation disturbances. CONCLUSION: (1) Selective multifetal pregnancy reduction in second trimester can feticide the abnormal fetus objectively or reduce the fetal number effectively. It is a safe procedure to decrease the complications of multifetal pregnancy and increase the birth weight. (2) If the intention is reducing the fetal number, we choose the fetus who lies in the fundus uteri and reduce the multifetal pregnancy to twins. (3) It is advised to aviod performing the procedure during vaginal bleeding. We reduce fetus after vaginal bleeding stops for one or more weeks. (4) Selective second-trimester multifetal pregnancy reduction will not result in the disturbance of blood coagulation and the death of remaining fetus. The incidence of pre-eclampsia is decreased after multifetal pregnancy reduction.

[Effect of Pulsatilla chinensis (Bunge) Regel saponins on eggs, miracidia and cercariae of Schistosoma japonicum].

OBJECTIVE: To investigate the effect of Pulsatilla chinensis (Bunge) Regel saponins (PRS) against the eggs, miracidia, cercariae of Schistosoma japonicum in vitro and compare its efficacy with praziquantel. METHODS: ICR mice were infected with the cercariae of S. japonicum by the patching abdominal method. The livers of the mice were grinded, screened, and then the eggs of S. japonicum were obtained 42 days post-infection. The miracidia were hatched by using the eggs, and the cercariae were obtained by using the infected Oncomelania snails on the light. The eggs, miracidia and cercariae of S. japonicum were incubated with 0, 1, 2, 3, 4, 5, 6, 7, 8 microg/ml PRS for different time, and praziquantel (PZQ) was used as the control. RESULTS: PRS suppressed the hatching rates of eggs for 24 h slightly superior to that of the control drug PZQ at different concentrations, especially in the 4 microg/ml concentration. After the miracidia were incubated with 1, 2, 3, 4, 5, 6, 7, 8 microg/ml PRS for 30 min, the dead rates of miracidia were 13.47, 26.05, 60.99, 90.84, 100, 100, 100, 100%, respectively. After the cercariae were incubated with 1, 2, 3, 4, 5, 6, 7, 8 microg/ml PRS for 30 min, the dead rates of cercariae were 5.32, 18.81, 44.7, 76.87, 98.28, 100, 100, 100%, respectively. PRS showed time- and dose-dependent mortality effects on the miracidia and cercariae of S. japonicum. CONCLUSION: PRS has the effects against eggs, miracidia, cercariae of S. japonicum in vitro, and it may become a new anti-schistosome agent.

[Effect of Pulsatilla chinensis (Bunge) Regel saponins against juvenile and adult Schistosoma japonicum in vitro].

OBJECTIVE: To explore the effect of Pulsatilla chinensis (Bunge) Regel saponins (PRS) against juvenile and adult Schistosoma japonicum and to compare its efficacy with praziquantel (PZQ) in vitro. METHODS: 3 h, 7 d, 14 d schistosomula and 42 d adult schistosomes were incubated with 0, 1, 5, 10, 20 and 30 microg/ml PRS for 4, 24, 48 and 72 hours, then the states of them were observed. The changes of the surface of S. japonicum incubated with 30 microg/ml PRS and PZQ within 4 hours were observed by a scanning electron microscope. RESULTS: The sensitivity of 3 h, 7 d, 14 d schistosomula and adults of S. japonicum to 1, 5, 10, 20, 30 microg/ml PRS displayed a time and dose dependence. All the worms died in 30 microg/ml PRS after 4 hours. The dead worm body appeared a gray-white color accompanied with their altered morphogenesis and opaque body. The tegumental surface of adults with different degrees of damages was observed by the electron microscope within 4 hours affected by PRS in vitro. CONCLUSIONS: The effects of PRS against S. japonicum in different developmental stages in vitro show that PRS may eventually have a therapeutic potential in the treatment or prevention of S. japonicum infection and is expected to become a new anti-schistosome drug.

Dihydroxyflavonol reduces post-infarction left ventricular remodeling by preventing myocyte apoptosis in the non-infarcted zone in goats.

BACKGROUND: Myocyte apoptosis is considered to be the major causative factor of left ventricular (LV) remodeling following myocardial infarction (MI). We previously reported that 3', 4'-dihydroxyflavonol (DiOHF), was able to suppress oxidative stress and preserve the expression of endothelial nitric oxide synthase during myocardial reperfusion injury, which may benefit the reduction of myocyte apoptosis. We therefore aimed to evaluate the potential actions of DiOHF against myocyte apoptosis and post-infarction LV remodeling in this study. METHODS: Following experimental MI, surgical instrumented goats were randomly assigned into vehicle and DiOHF (2 mg/kg; i.v., daily) groups to receive 4 weeks of reperfusion with corresponding treatments. LV pressure recordings and echocardiogram were performed at baseline, 2 and 4 weeks of reperfusion. Myocardial tissues were collected in the end to determine infarct size and apoptosis related assays. RESULTS: LV end-diastolic volume and diameter were significantly increased 4 weeks after MI in the vehicle group, accompanied by reduced posterior wall thickness, septal thickness and LV mass, whereas those changes were markedly prevented by DiOHF treatment. Similarly, significantly reduced infarct size was found in DiOHF group as compared to vehicle group, and DiOHF dramatically inhibited the increase in LV end-diastolic pressure and the reductions in ejection fraction, fraction shortening and dP/dt(max). Moreover, DiOHF treatment significantly reduced the extent of myocyte apoptosis detected by TUNEL assay, enhanced the protein expression of caspase-3, Fas, Bax and cytochrome c in the non-infarcted myocardium in comparison to vehicle. CONCLUSIONS: Daily DiOHF treatment during the reperfusion period after MI in the ovine hearts markedly reduced the magnitude of post-infarction LV remodeling through the inhibition of myocyte apoptosis in the remote non-infarcted myocardium.