New homoisoflavonoid analogues protect cells by regulating autophagy.

As a special group of naturally occurring flavonoids, homoisoflavonoids have been discovered as active components of several traditional Chinese medicines for nourishing heart and mind. In this study, twenty homoisoflavonoid analogues, including different substitution groups on rings A and B, as well as heteroaromatic B ring, were synthesized and evaluated for their cardioprotective and neuroprotective activities. In a H2O2-induced H9c2 cardiomyocytes injury assay, nine homoisoflavonoid analogues showed promising activities in the same level as the positive control, diazoxide. Six cardioprotective compounds with representative structure diversities were then evaluated for their neuroprotective effects on MPP+ induced SH-SY5Y cell injury model. Furthermore, autophagy inducing monodansylcadaverine (MDC) fluorescence staining methods and molecular docking studies indicated the action mechanism of these compounds may involve autophagy regulating via class I PI3K signaling pathway.

Long-term clinical outcomes of statin use for chronic heart failure: a meta-analysis of 15 prospective studies.

BACKGROUND: The effect of statin treatment on the long-term prognosis in patients with chronic heart failure (CHF) remains uncertain. This study aimed to answer the question by a meta-analysis. METHODS: The Cochrane databases, MEDLINE and EMBASE, were systematically searched. The eligibility of prospective studies that assigned CHF patients to receive statin treatment and a control (no statin treatment), had defined prognostic outcomes as primary endpoint, and had a minimal follow-up of 12 months was determined. RESULTS: Fifteen studies involving 45,110 patients were included in the analysis. Additional statin treatment was associated with reduced all-cause mortality (risk ratios [RR] = 0.71, 95% confidence intervals [CI] 0.61-0.83) and reduced rehospitalisation rate for heart failure (RR = 0.84, 95% CI 0.74-0.96). Statin treatment, however, had little impact on pump failure mortality, cardiovascular mortality, and sudden cardiac death. Atorvastatin treatment appeared to facilitate to reduce all-cause mortality (lnRR = 0.61, p = 0.05) and rehospitalisation for heart failure (lnRR = 0.44, p = 0.04) compared with non-atorvastatin therapy. CONCLUSIONS: Based on the available data, statins persistently decreased all-cause mortality and the incidence of rehospitalisation for heart failure in CHF patients, and the benefits might be partially associated with use of specific statin.

A new dicoumarinyl ether from the roots of Stellera chamaejasme L.

A new dicoumarinyl ether, 3-hydroxy-6-methoxy-7,7'-dicoumarinyl ether (1), was isolated from the roots of Stellera chamaejasme L, together with the known compound umbelliferone (2). Their structures were determined on the basis of spectroscopic techniques, including IR, NMR, and HR-ESI-MS.

Prognostic value of oxygen inhalation therapy for simple nocturnal hypoxemia in COPD: a meta-analysis.

Objective: The effect of oxygen therapy on the prognosis of chronic obstructive pulmonary disease (COPD) with nocturnal hypoxemia (NOD) has been controversial. Therefore, this study systematically evaluated the relevant literature and included it into randomized controlled studies for meta-analysis to evaluate the efficacy and prognosis. Methods: We searched PubMed, EMBASE, web of science, Cochrane, China HowNet and Wanfang database for the literature on the prognosis of COPD patients with simple NOD from the establishment of the database to 30 June 2022. The outcome indicators were death and aggravation of the disease. The efficacy evaluation measures were pulmonary function and arterial blood gas results. The publication bias and heterogeneity of the included studies were evaluated. Results: A total of 621 patients from 5 studies were included in this meta-analysis, and there was no publication bias in the included studies. The total mortality of long-term oxygen therapy (LTOT) in COPD patients with simple NOD in oxygen therapy group (RR = 1.04; 95% CI: 0.81-1.33, p = 0.77), mortality (RR = 0.87; 95% CI: 0.58-1.31, p = 0.50), risk of progression to LTOT events (RR = 1.07; 95% CI: 0.76-1.51, p = 0.71). PaO2 in patients with COPD and simple NOD in oxygen therapy group was higher than that in non-oxygen therapy group (mean difference (MD) = 13.47; 95% CI: 3.49-23.46, p = 0.008), the decrease of PaCO2 level was not statistically significant (MD = -10.05; 95% CI: -26.36-6.27, p = 0.23). Conclusion: Oxygen therapy can improve the prognosis of blood oxygen partial pressure in COPD patients with simple NOD, but oxygen therapy has no significant effect on the survival rate, controlling the progression of the disease to LTOT and reducing the partial pressure of carbon dioxide.

Sikokianin D, a new C-3/C-3"-biflavanone from the roots of Wikstroemia indica.

A new 3,3''-biflavanone, sikokianin D (1), was isolated from the roots of Wikstroemia indica, together with two known compounds. Their structures were elucidated by chemical evidence and spectral analyses, including HR-ESI-MS, and 1D- and 2D-NMR techniques.

[Determination of nine penicillin residues in milk by high-performance liquid chromatography-mass spectrometry].

OBJECTIVE: To establish a high-performance liquid chromatography-mass spectrometry (HPLC-MS/MS) method for detection of nine penicillin residues in milk. METHODS: The samples were precipitated with acetonitrile and degreased with n-hexane for pre-processing. The chromatography was performed by reversed-phase HPLC in a C18 column and eluted gradiently on line for 11 min. The mobile phases were water with formic acid (pH 3.1) and acetonitrile-water with formic acid (pH 3.1). By optimizing the mass condition, the method was operated by multiple-reaction monitoring (MRM) and quantitated by external standard calibration. RESULTS: The standard curves were linear in concentration range of 0.4 approximately 400 µg/L and all nine penicillins showed a good linear relationship in the milk matrix (r>0.990). The detection limit of the method was from 0.1 to 0.8 µg/L while the limit of quantification was from 0.3 to 2.6 µg/L. The average recoveries were higher than 80%. The within-day precisions were less than 8.5%. CONCLUSION: The established method is convenient, rapid and accurate and meets the requirement of monitoring penicillin residues in milk.

[A method for simultaneous assay of propulsion and absorption in small intestine].

OBJECTIVE: To develop a method for simultaneous assay of propulsion and absorption in small intestine. METHODS: The mice were administrated through gastric tube with mixed reagents containing 0.12% phenol red, D-xylose (1.25%, 2.5% and 5%) and 15% gelatin. The influence of phenol red on D-xylose absorption and the influence of D-xylose on small intestine propulsion rate were investigated by measuring serum concentration of D-xylose with phloroglucinol method. RESULTS: At 10 min, no significant difference was found between 5% D-xylose mixed reagent group and 5% D-xylose control. At 15 min, small intestine propulsion rate in 5% D-xylose mixed reagent group, but not in 2.5% and 1.25% D-xylose mixed reagent groups, was significantly higher than in phenol red control (P<0.05). CONCLUSION: Gastric administration of mixed reagent containing 0.12% phenol red, 5% D-xylose and 15% gelatin can simultaneously assay propulsion and absorption of small intestine in mice.

A New C-3/C-3"-Biflavanone from the Roots of Stellera chamaejasme L.

A new 3, 3"-biflavanone, neochamaejasmin C (1), was isolated from the roots of Stellera chamaejasme L., together with four known compounds. Their structures and configurations were elucidated by spectroscopic methods, including 2D-NMR techniques.

[Effect of purple sweet potato flavonoids on metabolism of glucose and lipids in diabetic rats].

OBJECTIVE: To investigate the effects of purple sweet potato flavonoids (PSPF) on blood glucose and lipids levels in diabetic rats. METHODS: Diabetes was induced by intraperitoneal injection of streptozotocin (STZ, 65 mg.kg(-1)) in rats. The changes of fasting blood glucose and lipids levels in serum and body weight, food and fluid intake of diabetic rats treated with PSPF were examined. RESULTS: Diabetic symptoms were ameliorated after rats were fed with PSPF. The fasting blood glucose (FBG), GSP, TC, TG, LDL-C were decreased and serum HDL-C levels were increased (P<0.01) in high, medium dose PSPF groups; while FBG, serum GSP, TG, LDL-C were also improved in low dose group (P<0.05 or P<0.01). CONCLUSION: Purple sweet potato flavonoids can decrease the blood glucose and lipids levels in diabetic rats.

[Components of myrsinane-type diterpenes from Euphorbia prolifera].

OBJECTIVE: To extract and isolate the component from myrsinane-type diterpenes of Euphorbia prolifera. METHODS: Petroleum extraction and chromatography on the silica gel were used to extract and isolate the diterpenes of Euphorbia prolifera. RESULTS: Eight components of myrsinol diterpenes were isolated, namely: Proliferin A(1), Proliferin B (2), Proliferin C(3), Proliferin D(4), Euphorprolitherin B(5), Euphorprolitherin D(6), SPr5(7) and 14-desoxo-3-O-prorionyl-5, 15-di-O-acetyl-7-O-nicotinoyl-myrsinol-14ß-acetate(8). Their structures were identified with mass-spectroscopic methods and NMR techniques. The cytotoxicity of compounds 1, 2, and 4 against cancer cells was evaluated, with compound 1 being active against A2780 cancer cells (IC(50) 7.7 µmol/L). CONCLUSION: Myrsinane-type diterpene Proliferin A from Euphorbia prolifera shows cytotoxic effect against human ovarian cancer cell line A2780.

Acetylation-dependent glutamate receptor GluR signalosome formation for STAT3 activation in both transcriptional and metabolism regulation.

Besides their original regulating roles in the brain, spinal cord, retina, and peripheral nervous system for mediating fast excitatory synaptic transmission, glutamate receptors consisting of metabotropic glutamate receptors (GluRs) and ionotropic glutamate receptors (iGluRs) have emerged to have a critical role in the biology of cancer initiation, progression, and metastasis. However, the precise mechanism underpinning the signal transduction mediated by ligand-bound GluRs is not clearly elucidated. Here, we show that iGluRs, GluR1 and GluR2, are acetylated by acetyltransferase CREB-binding protein upon glutamate stimulation of cells, and are targeted by lysyl oxidase-like 2 for deacetylation. Acetylated GluR1/2 recruit ß-arrestin1/2 and signal transducer and activator of transcription 3 (STAT3) to form a protein complex. Both ß-arrestin1/2 and STAT3 are subsequently acetylated and activated. Simultaneously, activated STAT3 acetylated at lysine 685 translocates to mitochondria to upregulate energy metabolism-related gene transcription. Our results reveal that acetylation-dependent formation of GluR1/2-ß-arrestin1/2-STAT3 signalosome is critical for glutamate-induced cell proliferation.

Rapamycin recruits SIRT2 for FKBP12 deacetylation during mTOR activity modulation in innate immunity.

The mammalian target of rapamycin (mTOR) is a serine-threonine kinase involved in cellular innate immunity, metabolism, and senescence. FK506-binding protein 12 (FKBP12) inhibits mTOR kinase activity via direct association. The FKBP12-mTOR association can be strengthened by the immunosuppressant rapamycin, but the underlying mechanism remains elusive. We show here that the FKBP12-mTOR association is tightly regulated by an acetylation-deacetylation cycle. FKBP12 is acetylated on the lysine cluster (K45/K48/K53) by CREB-binding protein (CBP) in mammalian cells in response to nutrient treatment. Acetyl-FKBP12 associates with CBP acetylated Rheb. Rapamycin recruits SIRT2 with a high affinity for FKBP12 association and deacetylation. SIRT2-deacetylated FKBP12 then switches its association from Rheb to mTOR. Nutrient-activated mTOR phosphorylates IRF3S386 for the antiviral response. In contrast, rapamycin strengthening FKBP12-mTOR association blocks mTOR antiviral activity by recruiting SIRT2 to deacetylate FKBP12. Hence, on/off mTOR activity in response to environmental nutrients relies on FKBP12 acetylation and deacetylation status in mammalian cells.

The role of iron in Parkinson's disease monkeys assessed by susceptibility weighted imaging and inductively coupled plasma mass spectrometry.

Mounting evidences indicated that elevated iron levels in the substantia nigra (SN) have been concerned as the underlying mechanisms of neurodegenerative diseases, including Parkinson's disease (PD). The present study used the 1-Methyl-4-phenyl-1, 2, 3, 6 -tetrahydropyridine (MPTP)-treated cynomolgus monkeys for PD to evaluate the usability of SWI for assessing iron deposition in the cerebral nuclei of PD. The results showed that susceptibility-weighted imaging (SWI) phase values of the ipsilateral (MPTP-lesion side) SN of MPTP-treated monkeys were lower than those in the contralateral SN of MPTP-treated monkeys and the same side of Control monkeys, suggesting that iron deposition were elevated in the affected side SN of MPTP-treated monkeys. Whereas MPTP has not effects on the SWI phase values in other detected brain regions of monkeys, including red nucleus (RN), putamen (PUT) and caudate nucleus (CA). Furthermore, ICP-MS results showed that MPTP increased the iron levels in MPTP injection side, but no in the ipsilateral striatum. Additionally, MPTP treatment did not affect the calcium and manganese levels in the detected brain regions of monkeys. However, Pearson correlation analysis results indicated that there were not relationship between SWI phase values in MPTP-lesion side of SN with the behavioral score, tyrosine hydroxylase (TH)-positive cells number and iron levels in the MPTP-lesion side of midbrain. Taken together, the results confirm the involvement of SN iron accumulations in the MPTP-treated monkey models for PD, and indirectly verify the usability of SWI for the measurement of iron deposition in the cerebral nuclei of PD.

[Variations of brain magnetic resonance imaging among manganese-exposed workers].

OBJECTIVE: Variations of the signal intensities in the magnetic resonance (MR) T(1)-weighted image (T(1)WI) of globus pallidus among manganese(Mn)-exposed workers were explored to provide a scientific basis for exposed biomarker of manganese-injured central nervous system (CNS). METHODS: The brain MR T(1) and T(2) WI in eighteen male asymptomatic Mn-exposed, eight manganism and nine healthy control workers were examined routinely by adopting a 1.5 Tesla signal superconducting system. The SIGP and the signal intensity in frontal white matter (SIFWM) in the same side were determined, then pallidal index (PI) was calculated. Concentration of MnO(2) in workplaces and content of manganese in red blood cell (MnRBC) among workers were respectively determined by flame atomic absorption spectrometer (AAS) and inductively coupled plasma-atomic emission spectrophotometry (ICP-AES). The follow-up investigation in the eight high Mn-exposed workers was made one year later. RESULTS: The results showed that the median of air MnO(2) in smelting workplace was 0.64 mg/m(3)(0.07 - 5.40 mg/m(3)), which were respective 0.56 mg/m(3)(0.09 - 1.71 mg/m(3)) in power distribution room (low Mn-exposure) and 0.89 mg/m(3) (0.07 - 5.40 mg/m(3)) in furnace (high Mn-exposure). PI in the Mn-exposed and high Mn-exposed workers were both higher than those of the manganism and control workers(116.4 +/- 8.2, 119.0 +/- 7.9, 105.3 +/- 8.4 and 102.2 +/- 1.5, respectively. Mn vs control, t' = 7.146, P = 0.000; Mn vs manganism, t = 3.181, P = 0.004. High Mn-exposure vs control, t' = 7.446, P = 0.000; high Mn-exposure vs manganism, t = 3.763, P = 0.001). The increased signal in T(1)WI of globus pallidus was observed in Mn-exposed workers, especially in high Mn-exposed workers. The content of manganese in red blood cell of Mn-exposed and control workers was significantly higher than those of the manganism workers [(151.6 +/- 40.5) ng/ml, (149.2 +/- 21.3) ng/ml, (154.5 +/- 46.6) ng/ml, (144.4 +/- 14.2) ng/ml, (20.8 +/- 7.4) ng/ml respectively. The difference was significant in statistics. Manganism vs control, t = 20.206, P = 0.000; manganism vs Mn, t' = 13.144, P = 0.000; manganism vs low and high Mn, t' = 12.964, 9.957, respectively, P = 0.000]. Only a decreased median of air MnO(2) in furnace was found one year later (0.89, 0.31 mg/m(3), Z = -2.142, P = 0.032). The difference was significant in statistics. CONCLUSION: Our data suggests that SIGP of MR T(1)WI among workers was obviously increased by manganese-exposure. PI may be taken as the signal of CNS injury which was induced by manganese-exposure.

[Effect of vitamin C and E on antioxidative enzyme, NOS activity and NO contents in hippocampus of rats with lead poisoning].

OBJECTIVE: To observe the effect of vitamin C and E on blood lead (Pb) levels and SOD, GSH-Px, NOS activity and NO, MDA content in hippocampus of rats with lead poisoning. METHODS: Rat lead poisoning model was established by oral administration of 0.615 mmol/L lead acetate in drinking water for 4 weeks; and animals were fed with vitamin C 100 mg/kg. bw and/or vitamin E 100 mg/kg. bw for 1 week. Then blood Pb levels and SOD, GSH-Px, NOS activity and MDA, NO contents in hippocampus of rats were determined by corresponding kits. RESULT: Compared with control group, blood Pb level was decreased significantly (P<0.05) after given vitamin C, vitamin E or combination of vitamin C and E. The concentrations of SOD, GSH-Px, NO and NOS were significantly higher in vitamin C and/or E groups than those in control group (P<0.05). The concentration of MDA in vitamin treatment groups was significantly lower than that in lead control group (P<0.05); furthermore concentration of MDA in combination of vitamin C and E group was significantly higher than that in vitamin C alone group (P<0.05). CONCLUSION: Administration of vitamin C and E can decrease blood lead level, alleviate damage of lipid peroxidation in hippocampus by lead toxicity and reverse NO, NOS levels in rats with lead poisoning.

[Separation and purification of proanthocyanidins from rose by macroporous resins].

OBJECTIVE: To study the separation and purification technology for proanthocyanidins from rose and establish the best operating conditions. METHODS: Evaluated by static adsorption capacity and elution ratio, five types of macroporous resins including D101, D1300, NKA, AB-8, NKA-II were tested to separate and purify proanthocyanidins. And evaluated by product purity, the concentration of extract sample, pH of extract sample, concentration of eluant and flow rate of elution had been investigated. RESULTS: D101 type macroporous resin showed the best property and was suitable for purifying proanthocyanidins from rose. The best operating conditions were as follows: 1.25 mg/ml as the concentration of extract sample, 2 as the pH value of extract sample, 70% ethanol equeous solution as the eluant and 2 ml/min as the flow rate of elution. CONCLUSION: This study can supply a method to separate and purify proanthocyanidins from rose.

Analysis of white matter characteristics with tract-based spatial statistics according to diffusion tensor imaging in early Parkinson's disease.

OBJECTIVE: To analyze the microstructure of brain white matter according to diffusion tensor imaging (DTI) based on tract-based spatial statistics (TBSS) in early Parkinson's disease (PD). MATERIALS AND METHODS: A total of 31 age- and sex-matched early PD patients and 22 healthy volunteers were recruited in the present study. DTI was performed, and the data analyzed with fsl4.0 software. The fractional anisotropy (FA) was compared between both groups with an independent t test, and the differential area was analyzed. White matter fiber tracts with significant difference in FA between the two groups were selected, and their FAs were measured. Pearson's correlation analysis was employed to analyze the unified Parkinson's disease rating scale (UPDRS) score and its association with FA of different tracts. RESULTS: When compared with healthy volunteers, early PD patients had reduced FA in the following areas: bilateral anterior corona radiate, upper corona radiate, fasciculus arcuatus, crus anterius capsulae internae, crus posterius capsulae internae, capsula externa, posterior thalamic radiation, optic radiation, sagittal layer (including fasciculus arcuatus and inferior fronto-occipital fasciculus), crura fornicis, stria terminalis, fornix, genu, body and pad of corpus callosum, left unciform fasciculus, right cingulate bundle, right medipeduncle, and arcuate fibers in the bilateral frontal, temporal, and occipital lobes (P < 0.05). When compared with healthy volunteers, early PD patients showed abnormal FA of fasciculus in the white matter mainly in following areas: bilateral crus anterius capsulae internae, bilateral capsula externa, right anterior corona radiate, body and pad of bilateral corpus callosum, and left sagittal layer (including fasciculi longitudinalis inferior and fasciculus occipitofrontalis inferior) (P < 0.05). In addition, in early PD patients, the UPDRS score and movement score had no relationship with the FA of different fasciculi in the white matter (P > 0.05). CONCLUSION: There is wide alteration of white matter microstructure in early PD patients, which is characterized by disruption of projection fibers in the descending pathway, limbic system-related fasciculi, corpus callosum, thalamus after radiation, posterior thalamic radiation, Gratiolet's bundle and other fasciculi in the white matter.

[Purification of total flavones from Morus alba L.by macroporous adsorbents and kinetic model for the process].

OBJECTIVE: To establish the separation and purification technology for the total flavones from Morus alba L.(MTF), and present a kinetic model for this process. METHODS: Three types of macroporous adsorbents were tested to separate and purify MTF, and to evaluated by adsorption capacity, elution ratio and product purity. The curves of dynamic adsorption-elution process was plotted and the kinetic equations were presented. RESULT: Among three types of macroporous adsorbents, the NKA-9 type showed better property with the adsorption capacity of 43.4 mg.g(-1)and the elution ratio of 98.2%. The purity of MTF product reached to 58.2 % in the technological conditions following: extract sample concentration of 20 mg.ml(-1), 6 times washing water and elution reagent of 70% ethanol. The adsorbent could be used for 4 times repeatedly. The kinetic equation was y=u(1 - e(-kx)). CONCLUSION: The NKA-9 type of macroporous absorbent is suitable to purify the MTF.

[Microwave-assisted extraction of flavonoids in Mulberry leaf and root-bark].

OBJECTIVE: To extract flavonoids in Mulberry leaf and White Mulberry root-bark by microuave-assisted method. METHODS: An orthogonal table was used to find the best procedure for microwave-assisted extraction (MAE) of flavonoids. The advantages of MAE were explored by comparing with the commonly used extraction methods. The different contents of flavonoids in Mulberry Leaf and Mulberry Root-bark were also compared. RESULTS: The best condition for procedure was extracting 20 min at 60 degrees C with 12 times of 70% ethanol. Among all factors, the ethanol concentration was significant This experiment implied that flavonoids in Mulberry leaf were 9 times as that in Mulberry Root-bark probably. Moreover, the flavonoids extracted from Mulberry Leaf and White Mulberry root-bark by MAE were 55% and 32% more than that from commonly used extraction method individually. CONCLUSION: MAE is advantageous than commonly used extraction method. It can be used for batch production.

Are Benign and Borderline Brain Tumors Underreported?

BACKGROUND: Primary benign and borderline (BB) brain tumors have been reportable since 2004 by population-based cancer registries in the United States. Because these tumors often are diagnosed clinically at nonhospital settings, underreporting is a big concern. Despite this, the magnitude and geographic variations in underreporting are unknown. The objectives of this study are to assess variations in BB brain tumor incidence rate by registry and trend in comparison to malignant brain tumors, as well as to identify the factors associated with the completeness of BB brain tumor reporting. METHODS: North American Association of Central Cancer Registries (NAACCR) Cancer in North America (CINA) Deluxe 1995­2012 Analytic File, which included data from 47 US population-based cancer registries, was used. Age-adjusted incidence rate and average annual percent change (APC) were calculated. Correlation coefficients were used to assess the relationships between incidence rates and clinical factors. RESULTS: The overall age-adjusted incidence rate was 14.2 per 100,000 for BB brain tumors and 6.6 per 100,000 for malignant brain tumors. The age-adjusted incidence rates of BB brain tumors varied by registry from 9.8 per 100,000 to 19.9 per 100,000, whereas the variations in malignant brain tumors were much smaller from 4.1 per 100,000 to 7.7 per 100,000. BB brain tumor cases were more likely than malignant brain tumors to be diagnosed through radiography without microscopic confirmation or surgery. Overall, the BB brain tumor incidence rate significantly increased by 2.3% per year from 2004 to 2012. In contrast, incidence rates of malignant brain tumors significantly decreased by 0.9% per year in the same period. Higher BB brain tumor incidence rates were significantly associated with higher proportions of cases without microscopic confirmation or surgery. These associations were not observed for malignant brain tumors. CONCLUSIONS: Incidence rates of BB brain tumors varied substantially across 47 US registries and were higher than those of malignant brain tumors in the United States. The variations in incidence rate of BB brain tumors may be largely attributable to difference in identifying clinically diagnosed cases. The increasing incidence rate of BB brain tumors may reflect improved case ascertainment rather than a biological trend. Key words: