Cancer, also known as malignant tumor, is the second largest disease after heart disease, which is characterized by genomic instability and mutagenicity. Ataxia telangiectasia and RAD3-related kinase (ATR) are members of phosphatidylinositol 3-kinase (PIKK) family, belonging to serine/threonine kinase, one of the key kinases in DNA damage response (DDR) and DNA repair pathway. This paper reviews the latest progress in the ATR inhibitor field including mechanism of action (MOA), therapeutic applications, and the combination therapy from the perspective of medicinal chemistry. It also discusses the possible challenges and future directions of developing ATR inhibitor antitumor drugs, which could provide the scientists in this field the convenience for access the information and application guidance for clinical studies.

Objective To explore the predictive value of brain lobe location of stroke lesion to development of long-term post-stroke depression(PSD)in the first-episode ischemic stroke patients for providing evidence for early intervention.Methods In the prospective study,158 patients aged 60 and over with first-episode ischemic stroke were continuously admitted into Department of Neurology of Shangqiu First People's Hospital from January 2013 to July 2013.The 2 to 3 years follow-up after stroke episode was performed in 126 cases for inquiring into correlation between brain lobe location of stroke lesion and development of PSD.The diagnosis of depression was in accordance with Mental Disorders Diagnostic and Statistical Manual 4(DSM-Ⅳ)standard,and divided into groups of stroke with depression(n=52)and stroke without depression(n=74).The degree of depression was evaluated by 17-item Hamilton Rating Scale for Depression(HAMD17).The location,number and volume of stroke lesions were determined by head MRI.The relationship between PSD and pathogenetic loci was analyzed by unconditional Logistic regression analysis.A difference in hemisphere commensalism.Results The morbidity of PSD was 41.3%(52/126),with 21.4%(27/126),12.7%(16/126),7.1%(9/126)in mild,moderate and severe PSD respectively.The frontal lobe(OR=2.824,95%CI=1.189-6.706)and the temporal lobe(OR=3.579,95%CI=1.233-10.393)cerebral infarction were correlated with the occurrence of PSD.The long-term PSD severity was more in frontal lobe than in temporal lobe(χ2=6.399,P<0.05).The average volume of cerebral infarction was larger in PSD group than in non-PSD group(t=3.271,P<0.05),and the average number of cerebral infarction loci was more in PSD group than in non-PSD group(t=3.176,P<0.05).The more severe the degree of depression according to HAMD17,the larger the average volume of cerebral infarction(F=6.280,P<0.05)and the more the average number of lesions(F=6.132,P<0.05).Conclusions The development of long-term PSD in the first-episode elderly patients is affected by the invasion site.The frontal lobe and temporal lobe infarction are independent risk factors for long-term PSD in patients with ischemic stroke,and the PSD was more severe in frontal lobe infarction than in temporal lobe infarction.

OBJECTIVE:To screen the α-glucosidase inhibitory active part from Pothos chinensis. METHODS:The aqueous extractions of P. chinensis were extracted by petroleum,ethyl acetate,n-butyl alcohol in turn to obtain different polarparts. Effect of each part on α-glucosidase inhibitory activity was determined,and enzyme inhibition kinetics was conducted for the screened parts with strong activity and relatively high yield rate;effects of each part on blood glucose level of mice loaded with glucose,su-crose and starch were respectively determined (using Acacoside tablet as positive control). RESULTS:Enzyme inhibition kinetics in vitro showed the ethyl acetate part [yield rate was 0.40%,enzyme activity inhibition rate was(72.90±2.85)%] had strongα-glu-cosidase inhibitory activity and showed a dose-dependent,fast,non-competitive and reversible model. Results of in vivo glucose tol-erance indicated that Acacoside tablet and each part of P. chinensis had no effects on blood glucose level of glucose-loaded mice (P>0.05);while Acacoside tablet and ethyl acetate part in P. chinensis could reduce 30,60 min blood glucose level of su-crose-loaded mice and 30,60,120 min blood glucose level of starch-loaded mice(P<0.05 or P<0.01). CONCLUSIONS:Ethyl acetate part is theα-glucosidase inhibitory active part from Yao medicine P. chinensis.

Mitochondrial dysfunction has been implicated in the aetiology of sporadic Parkinson's disease but its role in the disease mechanism remains unclear.To investigate the effect of synuclein on mitochondrial dysfunction induced by rotenone.The human dopaminergic SH-SY5Y cells were used as a cell model.The cells over-expressed the wild-type ?-synuclein were treated with complex I inhibitor rotenone.The cell viability,complex I activity,Mitochondrial swelling and O2-content were tested at different time point-1w,2w,4w after rotenone treated.CCK-8 test results showed that the cell viability of overexpressed ?-synuclein(SH-SY5Y-Syn)was much lower than the control group(SH-SY5Y-Ctr).After administrating with rotenone about 1w or 2w the cell viability of SH-SY5Y-Syn became higher than that of SH-SY5Y-Ctr.On the 4th week the results were contrary to the first 2 weeks.Similar results were got when test the mitochondrial function.In the first 2 weeks after roteoone administrating,the mitochondrial function of SH-SY5Y-Syn was better than that of SH-SY5Y-Ctr.This suggest that the ?-synuclein could protect the mitochondrial against the injury induced by rotenone in the early stage-1w,2w,while this effect disappeared in the final stage-4w.

After a study on the characteristic of ECG data, we propose here in this paper a lossless compression method of ECG data, which is based on JPEG2000. It integrates both 1D and 2D compression. The method has been verified through all forty-eight records in MIT-BIH Arrhythmia database. And the result shows that the method has a better compression rate and a good computational efficiency.
Algorithms ; Electrocardiography ; methods ; Image Processing, Computer-Assisted

Adolescent ; Adult ; Antiviral Agents ; therapeutic use ; Collagen Type IV ; blood ; DNA, Viral ; blood ; Female ; Hepatitis B, Chronic ; blood ; drug therapy ; pathology ; Humans ; Hyaluronic Acid ; blood ; Interferon-alpha ; therapeutic use ; Laminin ; blood ; Male ; Middle Aged

The present study aims to investigate the lignan constituents from Sambucus williamsii and their proliferation effects on osteoblast-like UMR106 cells. Seven compounds were isolated and purified by macroporous resin D101, silica gel, Sephadex LH-20, Toyopearl HW-40, ODS column chromatographies and Preparative HPLC(C-18). Their structures were elucidated by spectroscopic methods as threo-guaiacylglycerol-beta-0-4'-conifery ether (1), lirioresinol A (2), 1-hydroxypinoresinol (3), 5-methoxybalanophonin (4), balanophonin (5), 5-methoxy-trans-dihydrodehydrodiconiferyl alcohol (6), and p-hydroxybenzaldehyde (7). Compounds 3-7 were obtained from this genus for the first time. The proliferation effects of all isolated compounds on osteoblast-like UMR106 cells were determined. Compounds 1-7 (1 x 10(-12)-1 x 10(-7) mol x L(-1)) increased UMR106 cell proliferation to some extent.
Cell Line ; Cell Proliferation ; drug effects ; Lignans ; isolation & purification ; pharmacology ; Osteoblasts ; cytology ; drug effects ; Plant Stems ; chemistry ; Sambucus ; chemistry

ObjectiveNotch signaling is highly conservative in evolution and plays an important role in cell's proliferation and differentiation.Construction of tentiviral vector containing Notch intracellular domain (NICD) would lay the foundation for the study of Notch signaling.MethodsTotal RNA was extracted from the myeloid tissue of C57BL/6 mice.cDNA was composed via reverse transcription.NICD sequence was obtained by PCR and recombined into lentiviral vector.Lentiviral vector with NICD was infected into target HEK293T cell.Real-time PCR and Western blot were used to examine NICD expression in HEK293T cell.ResultsNICD expression increased in HEK293T cells.ConclusionThe successful construction of lentiviral vector involving mice NICD expression provides the foundation for the future study.

50%.The patients were categorized into as:one-,two-, and three-vessels coronary artery disease group.Central aortic SBP and DBP was measured by cathetarization dur- ing angiography of coronary artery and brachial blood pressure was measured using cuff method.Results Periph- eral SBP,PP and ascending aortic SBP,PP,fractional systolic pressure(FSP=SBP/MAP)were increased and as cending aortic fractional diastolic pressure(FDP=DBP/MAP)was reduced when the diseased coronary vessels were increased(P

When the glomerular mesangial cells of rats were cultured in vitro at high glucose concentration,the activity of extraeellular signal-regulated kinase(ERK),the expression of transforming growth factor-?_1(TGF-?_1)mRNA and the content of typeⅣcollagen in the supematant were higher than those at normal glucose concentration.These effects were inhibited by fluvastatin.The results showed that the activation of ERK signal transduction pathways appeared to play a role in the onset and progression of diabetic nephropathy. Furthermore,fluvastatin could protect the kidney by inhibiting ERK signal transduction pathway and TGF-?_1 expression.