In this paper, fourteen new L-proline derivatives were designed and synthesized, and their acetlcholinesterase (AChE) inhibitory activities were also investigated in vitro. New L-proline derivatives were prepared from substituted 2-bromo-1-acetophenones through four-step reaction; and their bioactivities as AChE inhibitors were measured by Ellman spectrophotometry. The results showed that the target compounds had a certain AChE inhibitory activity to in vitro. The bioactivity of compound 8b was the best of them, and its IC50 value was 5.45 µmol.L-1, which was better than that of rivastigmine. So the acetylcholinesterase inhibitory activities of new L-proline derivatives were worth to be further studied.
Acetylcholinesterase ; Cholinesterase Inhibitors ; chemical synthesis ; chemistry ; Drug Design ; Proline ; analogs & derivatives ; Rivastigmine ; chemistry ; Structure-Activity Relationship

Objective To investigate the value of three-dimensional speckle tracking imaging (3D-STI) in assessment of left ventricular (LV) strains. Methods Thirty healthy young adults examined by two-dimensional speckle tracking imaging (2D-STI) and 3D-STI. And the results of LV measurements were compared, which included mean peak systolic longitudinal strains, radial strains and circumferential strains. Also, the time consumption of these two methods was compared. Results The time needed for 3D-STI in acquisition and analysis of the images were (309.3±23.4)s, (305.5±11.2)s, while the time for 2D-STI were (490.6±14.4)s, (1261.4±39.9)s. The differences were signiifcant(t=-21.81, 69.94, both P<0.01). The global mean peak systolic radial strains was (48.59±7.68)%by 3D-STI and (33.25±7.27)%by 2D-STI. The difference was signiifcant(t=9.16, P<0.01). The global mean peak systolic longitudinal and circumferential strains were (-17.66±3.14)%, (-17.13±2.29)% by 3D-STI and (-21.35±2.46)%, (-21.97±3.84)% by 2D-STI. The differences were signiifcant(t=5.33, 5.99, both P < 0.01). The 3D-STI strains were different at different levels of LV. The longitudinal, circumferential and radial 3D-STI strains were largest at middle levels. However, 2D-STI strains didn′ t show such trend. Peak strains measured by 3D-STI and 2D-STI showed high inter-observer and intra-observer agreement in Bland-Altman chart. Conclusion 3D-STI is a novel, convenient and reproducible method to evaluate the strains of LV.

Poly (2-ethylacrylic acid) (PEAA) alkylamide derivatives were synthesized for constructing pH-sensitive liposomes by partially modification of carboxylic groups of PEAA with chemical reaction. These lipid derivatives of PEAA were synthesized by partially modification of carboxylic groups of PEAA with alkylamines. The acid-sensitive polymer associated liposomes were obtained by the method of polymer self-insertion in aqueous solutions through inserting hydrophobic lipid anchors of the polymer PEAA derivatives into the outer layer of vesicles. Factor effects on polymer insertion into liposomes were evaluated and the pH-sensitivity of the polymer associated liposomes was studied by calcein release assay. The PEAA-assoeiated-liposomes were prepared successfully by the methods of self-insertion. The PEAA-associated-liposomes are shown to be stable at neutral pH. (1) There was no correlate of anchor density of PEAA with length of the alkyl chain, but was positively correlated with the degree of PEAA modification. (2) Polymer insertion increased with initial ratio of polymer to lipid. (3) Unerting hydrophobic lipidr acidic conditions the associated polymer induces membrane disruption and fusion. (4) The PEAA-associated-liposomes shown pH-sensitive drug release property under acidic conditions. The anchored-poly (ethylacrylic acid) lipid derivatives can be useful in developing a potential pH sensitive drug delivery system.
Acrylates ; chemical synthesis ; pharmacokinetics ; Animals ; COS Cells ; Cercopithecus aethiops ; Drug Delivery Systems ; methods ; Fluoresceins ; metabolism ; Hydrogen-Ion Concentration ; Liposomes ; chemistry ; pharmacokinetics ; Particle Size ; Polyunsaturated Alkamides ; chemical synthesis ; pharmacokinetics

OBJECTIVETo compare the differentiation ability difference of hematopoietic, mesenchymal and endothelial potential between CD41⁺ cells derived from the mouse aorta-gonadmesonephros (AGM) region, yolk sac (YS) and embryonic circulating blood (CB).

METHODSCD41⁺ cells were sorted from AGM, YS and CB. The CD45 and c-kit expression were studied in CD41⁺ cells by flow cytometry. IL-3 and bone morphogenetic protein 4 (BMP-4) treatment together with semi solid culture were used to assess hematopoietic potential difference of CD41⁺ cells. Immunofluorescence staining of α-SMA was used to assess mesenchymal potential difference. The endothelial cell induction system was used to assess endothelial potential difference.

RESULTSThe proportions of CD45+ cells in CD41⁺ population were 51.9% (AGM), 45.8% (YS) and 22.2% (CB), respectively, while those of c-kit⁺ cells were 40.0% (AGM), 39.6% (YS) and 36.2% (CB), respectively. After stimulated by IL-3 factor, the number of total colonies increased in all three groups-derived CD41⁺ cells compared to that of unstimulated group[(14.1±1.9) vs (1.2±0.2), (32.4±1.1) vs (18.4±2.2) and (41.8±0.9) vs (10.4±1.8)], (P<0.01). After stimulated by BMP-4 factor, compared to unstimulated group, CFU-Mix colony number in CD41⁺ cells from AGM region and YS were significantly decreased[(0.5±0.6) vs (3.2±0.8), (1.3±0.7) vs (7.4±1.7)](P<0.01), but there was no difference in CB group[(2.5±0.5) vs (3.9±1.5)](P>0.01). The mesenchymal marker α-SMA was highly expressed in CD41⁺ cells from AGM region and YS, but lowly expressed in CD41⁺ cells from CB.

CONCLUSIONThere are some differences between CD41⁺ cells in AGM region, YS and CB on hematopoietic cell surface marker expression, hematopoietic colony formation with IL-3 and BMP-4 stimulation.

Animals ; Aorta ; cytology ; Bone Morphogenetic Protein 4 ; pharmacology ; Cell Differentiation ; Gonads ; cytology ; Interleukin-3 ; pharmacology ; Mesonephros ; cytology ; Mice ; Platelet Membrane Glycoprotein IIb ; metabolism ; Proto-Oncogene Proteins c-kit ; metabolism ; Yolk Sac ; cytology

Objective To investigate the prevalence and influencing factors related to abuse and negligence against the elderly in the rural areas. Methods 975 elderly over 60 years from 41counties in Anhui province were included. All participants completed an anonymous questionnaire including items as: educational background, marital condition, income, child-discipline, rude action to parents, daily activities, physical functions, having chronic illness, abuse and negligence against the elderly, etc. Results In the last year, rates of common physical abuse, serious physical abuse,emotional abuse, financial exploitation, negligence, overall abuse and negligence against the elderly were 4.5%, 1.5%, 26.9%, 4.9%, 7.2%, 29.9% respectively. Among the 281 victims, 80.4% reported that they were suffered more than 3 times of abuse and neglect episodes, and 34.9% reported that they were suffered more than 2 forms of abuse and negligence. The primary sadism was carried out by the daughter-in-law or son-in-law (43.2%) of the elderly. Low activity on daily life and having chronic illness were the risk factors causing common physical abuse while better education was the protective factor to it, Low ability in managing daily activity of living was the risk factor causing serions physical abuse. Less active on daily life and having rude action to parents were the risk factors to emotional abuse, but being strict with their children was the protective factor to emotional abuse. Less active on daily life, often beating their children and having rude action to parents were the risk factors related to financial exploitation. Less active on daily life, having rude action to parents and having bad physical functions were the risk factors causing negligence. Less active on daily life and having rude manner to parents were the risk factors of overall elderly abuse and negligence, but being strict with their children was protective factor to the abuse and negligence against the elderly. Conclusion High prevalence on abuse and negligence against the elderly was seen in the rural areas of China. Different forms on elderly abuse and negligence were affected by different factors that called for more attention to be paid to those elderly with lower ability in managing their daily life.

Aim To observe the absorption activity of five components of Polygonum orientale L. Flower ex-tract in Caco-2 cell monolayer. Methods The effects of different concentrations, time, temperature, pH and P-glycoprotein inhibitors on Caco-2 cells were investi-gated by UPLC-MS/MS. Results The absorption of five components of Polygonum orientale L. Flower ex-tract presented a concentration-and time-dependent manner, and the uptake of quercetin was reduced in Caco-2 cells after 90 min. There was a highest intake at 37℃,and the uptake of four components was best in acid environment except for the quercetin at pH 6 , which was best at pH5 . The uptake of quercetin and kaempferol was significantly improved after the addition of P-glycoprotein inhibitors of verapamil. Conclusions The cellular uptake mechanisms of the five compo-nents of Polygonum orientale L. Flower extract is man-inly through passive diffusion. P-glycoprotein is in-volved in the uptake of quercetin and kaempferol.

Objective To investigate the demographic features, etiology and clinical characteristics of chro-nic pancreatitis ( CP) .Methods We retrospectively analyzed the records of 346 CP cases hospitalized in Peking Union Medical College Hospital during the period of January 1983 to December 2008, summarizing the demographic features, clinical manifestations, causes of disease, and complications of these patients.Results The 346 CP ca-ses included 267 males and 79 females ( M/F ratio=3.38∶1 ) .The mean age of onset was ( 44.34 ±15.88 ) years.Most of the patients were Han Chinese ( 94.80%, 328/346 ) , and a large proportion were cadres (32.08%, 111/346) .Both the number of CP cases and its proportion in the total number of inpatients in the hospital increased rapidly.Alcohol (40.17%) and cholelithiasis (41.04%) were the most common risk factors of CP.CP of different etiologies had all increased, especially alcoholic CP, growing by an mean annual rate of 108.7%.84.39% (292/346) of the patients presented with abdominal pain, 56.07%(194/346) had weight loss, 24.86%(86/346) had jaundice (all obstructive).Diabetes (25.14%, 87/346) was the most common complication.The median time of CP onset to occurrence of diabetes and fatty diarrhea were 1.00 year and 280.03 months, respectively.Diabetes occurred earlier in patients with autoimmune pancreatitis than those with idiopathic pancreatitis (P=0.020).Conclusions The incidence of CP is growing rapidly in China, with alco-holic CP increasing faster than biliary CP.The most common symptoms of CP are abdominal pain and weight loss, while the most common complication is diabetes.A patient database and regular follow-up visits could contribute to better understanding of epidemiological patterns of CP and improvement of its diagnosis and treatment.

As one of the most frequent complications of diabetes, diabetic neuropathy often involves peripheral and central nervous systems. Neuroinflammation is the key pathogenic factor of secondary nerve injury in diabetes. NOD-like receptor pyrin domain-containing 3(NLRP3) inflammasome is a group of subcellular multiprotein complexes, including NLRP3, apoptosis associated speck-like protein(ASC), and pro-cysteinyl aspartate specific proteinase 1(pro-caspase-1). NLRP3 inflammasome is an inducer of innate immune responses. Its activation stimulates the inflammatory cascade reaction, promotes the release of inflammatory mediators, triggers cell death and uncontrolled autophagy, activates glial cells, facilitates peripheral immune cell infiltration, and initiates amyoid β(Aβ)-tau cascade reactions. As a result, it contributes to the central nerve, somatic nerve, autonomic nerve, and retinal nerve cell damage secondary to diabetes. Therefore, due to its key role in the neuroinflammation responses of the body, NLRP3 inflammasome may provide new targets for the treatment of diabetic neuropathy. With multi-target and low-toxicity advantages, traditional Chinese medicine plays a vital role in the treatment of diabetic neuropathy. Accumulating evidence has shown that traditional Chinese medicine exerts curative effects on diabetic neuropathy possibly through regulating NLRP3 inflammasome. Although the role of NLRP3 inflammasome in diabetes and related complications has been investigated in the literature, systematical studies on drugs and mechanism analysis for secondary neuropathy are still lacking. In this article, the role of NLRP3 inflammasome in diabetic neuropathy was explored, and the research progress on traditional Chinese medicine in the treatment of diabetic neuropathy through NLRP3 inflammasome was reviewed.
Humans ; Inflammasomes/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Diabetic Neuropathies/drug therapy* ; Medicine, Chinese Traditional ; Neuroinflammatory Diseases ; Inflammation ; Diabetes Mellitus

Objective:To study the effect of different hormone ratios on the callus induction of roots,stems and leaves of Polygala tenuifolia,and determine and analyze the amount of flavonoids in roots,stems and leaves of P. tenuifolia. Method:With MS as the basic medium and roots,stems and leaves of P. tenuifolia sterile seedings as explants,the effects of 2,4-D,NAA and 6-BA on callus induction and flavonoid accumulation in different parts of roots,stems and leaves of P. tenuifolia were determined by orthogonal test. Result:2,4-D,NAA and 6-BA had significant effects on the callus induction rate of roots,stems and leaves of P. tenuifolia. The optimal callus induction combination of leaves was MS+3.0 mg·L^-1 2,4-D+1.0 mg·L^-1 NAA+1.5 mg·L^-1 6-BA,the optimal callus induction combination of stems was MS+1.0 mg·L^-1 2,4-D+3.0 mg·L^-1 NAA+1.5 mg·L^-1 6-BA,the optimal callus induction combination for roots was MS+1.0 mg·L^-1 2,4-D+1.0 mg·L^-1 NAA+1.0 mg·L^-1 6-BA. And 2,4-D,NAA and 6-BA had significant effects on flavonoid accumulation in the stem callus of P. tenuifolia,and MS+3.0 mg·L^-1 2,4-D+1.0 mg·L^-1 NAA+0.5 mg·L^-1 6-BA was the best flavonoid accumulation combination.NAA,6-BA had significant effects on flavonoid accumulation in the leave callus of P. tenuifolia,while 2,4-D had no significant effect,and MS+3.0 mg·L^-1 2,4-D+2.0 mg·L^-1 NAA+1.0 mg·L^-1 6-BA was the optimal flavonoid accumulation combination,the three hormones had no significant effect on the accumulation of flavonoids in the root callus of P. tenuifolia,and MS+2.0 mg·L^-1 2,4-D+1.0 mg·L^-1 NAA+1.5 mg·L^-1 6-BA was the best flavonoid accumulation combination. Conclusion:Under the conditions,the callus induction rate of roots,stems and leaves of P. tenuifolia is 100%, especially, the callus of P. tenuifolia leaves was the optimal,which is followed by P. tenuifolia stems and P. tenuifolia roots. Under the conditions,the amount of flavonoids in roots,stems and leaves of P. tenuifolia reach 21.31,24.56,23.61 mg·g^-1,respectively.

Rosmarinic acid is one of anti-tumor ingredients in the Sarcandra glabra. After treatment with 0, 10, 30, 90, 270 and 810 μmol·L⁻¹ rosmarinic acid for 24, 48, 72 hours respectively, the inhibitory effects on MCF-7 and MDA-MB-231 cells were observed by CCK-8 and cell wound healing test. No significant inhibition effecton proliferation and migration was observed in MCF-7 cell. However, 90, 270 and 810 μmol·L⁻¹ rosmarinic acid could inhibit the proliferation and migration of MDA-MB-231 cells in a dose-dependent and time-dependent manner. Flow cytometry was further used to detect apoptosis ratios of MDA-MB-231 cells after Annexin V-FITC/PI staining, and significant apoptosis was observed after rosmarinic acid treatment. Real-time PCR and Western blot tests were carried out to detect the expressions of apoptosis-related genes. The down-regulation of the Bcl-2 expression and the up-regulation of the Bax expression were observed in MDA-MB-231 cells after rosmarinic acid treatment. The results suggested that rosmarinicacid can inhibit the proliferation and migration, and induce the apoptosis of MDA-MB-231 cells, which may be correlated with the down-regulation of Bcl-2 gene and the up-regulation of Bax gene.