Protein-protein interactions(PPI)with large and shallow interfaces are generally undruggable targets. Many PPI in-volved in vital biological processes are mediated by helixes,therefore PPI can be easily targeted by helical epitope mimics. However, the application of peptide was limited by its conformational flexibility and low stability until the significant work was done by Arora ,et al who applied nucleation and crosslinking strategies to lock peptides in helical conformation. The conformation-locked strategies helps to improve peptide stability,cell permeability,and afterwards target intracellular PPI. At present,the conformation-locked strategies of peptides have achieved great development,and have become a hot spot in peptide research field. In this paper,the recent develop-ment,centering nucleation strategies,applications and bright prospects of helical conformation-locked peptides,are reviewed in order to provide theoretical basis for drug design based on PPI.

OBJECTIVETo investigate the effect of the combination therapy of biofeedback with electrical stimulation on chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) through clinical trials.

METHODSA total of 140 cases of diagnosed CP/CPPS were randomly divided into a control group (n = 20), a biofeedback group (BF, n = 40), an electrical stimulation group (ES, n = 40), and a biofeedback plus electrical stimulation group (BF + ES, n = 40). The latter three groups were treated by corresponding methods 5 times a week for 2 weeks, while the controls left untreated. After the treatment, all the patients were followed up for 30 days. The NIH chronic prostatitis symptom index (NIH-CPSI) scores and the results of uroflowmetry were obtained and compared before and after the treatment.

RESULTSCompared with the control group, the scores on pain, urinary symptoms and quality of life (QOL) and the total NIH-CPSI scores were obviously decreased (P < 0.05), and the maximum flow rate (MFR) markedly improved (P < 0.05) in the BF, ES and BF + ES groups after the treatment, with significant differences between the former two and the latter one (P < 0.05), but not between the BF and ES groups (P > 0.05), nor in the control group before and after the treatment (P > 0.05).

CONCLUSIONThe combination therapy of biofeedback with electrical stimulation has a synergistic effect on CP/CPPS by alleviating pain and urinary symptoms, improving QOL and elevating MFR.

Adolescent ; Adult ; Biofeedback, Psychology ; Chronic Disease ; Electric Stimulation ; Humans ; Male ; Middle Aged ; Pelvic Pain ; therapy ; Prostatitis ; therapy ; Syndrome ; Young Adult

OBJECTIVETo evaluate the effects of W-7, a calmodulin inhibitor, on transmural dispersion of repolarization (TDR), early after depolarization (EAD) and torsade de pointes (TdP) induction after administration of d-sotalol in isolated rabbit heart.

METHODSTdP was induced by d-sotalol (30 micromol/L), bradycardia, and hypokalemic (1.5 mmol/L)/hypomagnesaemic (0.35 mmol/L) solution in isolated female rabbit hearts. Thirty six rabbit hearts were divided into 4 groups (n = 9 each): d-sotalol alone, d-sotalol + W-7 (20 micromol/L), d-sotalol + W-7 (50 micromol/L), and d-sotalol + W-7 (100 micromol/L). Monophasic action potentials (MAPs) of the left ventricular epimyocardium (Epi), midmyocardium (M), and endomyocardium (Endo) were recorded simultaneously with ECG. The incidence of EAD and TdP were observed as well.

RESULTSTreatment with d-sotalol alone prolonged ventricular MAP duration and QT interval, increased TDR, and evoked high incidence of EAD (9/9) and spontaneous TdP (7/9) in hypokalemic/hypomagnesaemic solution in female rabbit heart. W-7 concentration-dependently decreased incidence of TdP (4/9 in 20 micromol/L; 2/9 in 50 micromol/L; 1/9 in 100 micromol/L). This effect of W-7 coincided with the decreased incidence of EAD (5/9 in 20 micromol/L; 4/9 in 50 micromol/L; 1/9 in 100 micromol/L). However, the d-sotalol-induced prolongation of QT interval and TDR was not significantly altered by W-7 at the three concentration used.

CONCLUSIONSIn isolated female rabbit hearts, calmodulin antagonist W-7 suppresses d-sotalol-induced TdP without altering TDR but does suppress EAD. The effects observed with W-7 also suggest a possible important role for calmodulin-activated enzymes in the induction of TdP.

Animals ; Calmodulin ; antagonists & inhibitors ; Enzyme Inhibitors ; therapeutic use ; Female ; In Vitro Techniques ; Rabbits ; Sotalol ; adverse effects ; Sulfonamides ; therapeutic use ; Torsades de Pointes ; chemically induced ; prevention & control

OBJECTIVETo study the anti-tumor effects of all-trans retinoic acid (ATRA) and mechanisms of its action.

METHODSHuman esophageal carcinoma cell line EC9706 cells were treated with ATRA at different concentration. The proliferation inhibition was examined by MTT assay. Morphological examination, TUNEL method and flow cytometry were used to detect the apoptosis and changes of cell cycle. Immunohistochemical method was used to detect the expression of apoptosis-related genes caspase-3 and bcl-2. The semi-quantification of protein expression was analyzed by pathological image analysis.

RESULTSATRA inhibited the proliferation of EC9706 cells moderately. Apoptosis in EC9706 cells was induced by ATRA treatment. The morphology of EC9706 cells showed changes such as nuclear chromatin condensation and fragmentation. Sub-G1 peak was found by flow cytometry. The maximal apoptosis rate was 32.6%. The expression of caspase-3 gene was enhanced. The expression of bcl-2 gene was decreased. All these effects were presented in a dose-dependent and time-depend manner.

CONCLUSIONApoptosis is one of the key mechanisms of ATRA action on EC9706 cells.

Antineoplastic Agents ; administration & dosage ; pharmacology ; Apoptosis ; drug effects ; Caspase 3 ; metabolism ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Dose-Response Relationship, Drug ; Esophageal Neoplasms ; metabolism ; pathology ; Humans ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Tretinoin ; administration & dosage ; pharmacology

Objective To compare the amplitude of the SK2 current (small conductance calciumactivated potassium channel ) in human atrial myicytes with or without persistent atrial fibrillation(AF).Methods Right atrial appendage was obtained from 15 patients with sinus rate (SR) and 7 patients with AF underwent surgical valve replacement. Single myocyte was isolated by enzymatic dissociation method and the SK2 channel current density was recorded using whole-cell patch clamp techniques to detect the changes.Immunofluorescence was used to observe SK2 channel protein distribution on right atrial appendage. Results Using the whole cell patch-clamp recording techniques, an inward rectifier K+ mix currents could be obtained from both SR (n = 15 ) and AF (n =7 ) samples, IK1 mix currents density in single myocyte of AF group was significantly increased than in SR group [( - 16. 42 ±5.32) pA/pF vs ( -6. 59 ±2. 24) pA/pF,P ＜0. 01], which could be partially inhibited by apamin (100 nmol/L). The apamin-sensitive current was obtained by subtraction of the currents before and after treatment with apamin. SK2 current density was significantly increased in AF group than that of SR group [( - 9. 81 ± 2. 54) pA/pF vs ( - 3.67 ± 0. 37)pA/pF,P ＜ 0. 01]. SK2 channel protein was evidenced with immunofluorescence method in right atrial appendage from AF group and SR group. Conclusion SK2 channel protein and current were present in atrial myocytes. The SK2 current density was significantly increased in AF group than in SR group suggesting that the increase of SK2 current might contribute to the electrical remodeling in AF patients.

Objective:To understand the oral health status of urban and rural residents in China,the Fourth National Oral Health Epidemiological Survey (FNOHES) was conducted in 2015.Materials and methods:Based on the principles of multi-stage,stratified,equal capacity,and random sampling,the subjects included five groups of residents aged 3-5,12-15,35-44,55-64,and 65-74 years in all 31 provinces,municipalities,and autonomous regions except Hong Kong,Macao,and Taiwan.The total sample size was 172,425.The survey covered two areas,namely oral health status and knowledge,attitude and oral health behavior.Results:Residents in China had serious caries and poor periodontal condition.The prevalence of caries was above 50％ in all age groups,subjects without periodontal disease accounted for ＜50％,and fewer than 50％ of subjects brushed their teeth twice a day.Based on the results of the FNOHES,the following suggestions were proposed for improving the oral health in China in the future:to establish and improve the comprehensive prevention and control system for oral diseases,implement a comprehensive prevention and control strategy for priority groups,strengthen the oral health education for all people to improve oral health literacy,enhance dynamic monitoring to scientifically evaluate oral health status,and coordinate multi-party resources to establish and improve the oral health service security system.Conclusion:The oral health status of Chinese residents and their oral health behavior habits need to be improved.With the support of the administrative departments of the government and unremitting efforts of the oral health staff,all sectors of society must be coordinated to strengthen oral health education for the whole population.Furthermore,comprehensive prevention and control measures must be implemented for priority groups.

To investigate the characteristics of action potentials and their ionic mechanism in cardiomyocytes from rabbit pulmonary vein sleeves (PVC), and to compare them with those in left atrial cardiomyocytes (LAC), the technique of whole-cell patch clamp was applied. We used current-clamp technique to record action potentials, and voltage-clamp technique to record ionic currents. PVC had longer action potential duration (APD) than LAC, and therefore a second plateau response could be induced easily, suggesting a strong tendency of early afterdepolarization (EAD) genesis in PVC. Non-selective cation current (I(NSCC)) was first recorded in both LAC and PVC. This I(NSCC)was permeable to K(+), Na(+) and Cs(+), sensitive to GdCl3 but not sensitive to 4-AP. The current densities of inward rectifier potassium current (I(K1)), transient outward potassium current (I(To)) and I(NSCC) were all significantly less in PVC than those in LAC. These differences in repolarizing ionic currents between PVC and LAC form a basis of the differences in their action potential configurations and might be an important ionic mechanism of the arrhythmogenic characteristics of pulmonary vein muscle sleeves.
Action Potentials ; physiology ; Animals ; Atrial Fibrillation ; physiopathology ; Myocytes, Cardiac ; metabolism ; physiology ; Patch-Clamp Techniques ; Potassium Channels, Inwardly Rectifying ; metabolism ; physiology ; Pulmonary Veins ; cytology ; physiology ; Rabbits ; Shal Potassium Channels ; metabolism ; physiology

OBJECTIVESelecting variable-number tandem-repeat (VNTR) loci for different serogroups of Shigella spp to explore and establish multilocus variable-number tandem-repeat analysis (MLVA) method, in order to study the molecular characteristic of the isolated strains.

METHODSOf the Shigella strains found by dysentery surveillance in Beijing from 2001 to 2009, 180 strains were selected for this study, according to the number and serotypes of the surveillant strains, at the ratio of 15%; including 50 strains of Shigella sonnei and 130 strains of Shigella flexneri. After screening the polymorphism of the 18 VNTR loci, 10 VNTR loci (sh1-sh10) were retained and constructed three groups of multi-PCR methods to detect all he 180 strains and analyze MLVA molecular subtypes using capillary segments.

RESULTSA range of 2 to 11 alleles were found on the 10 VNTR loci among the 180 Shigella strains, with a diversity index value between 0.158 and 0.766. The 10 loci showed diversity in different serogroups, such as only one allele found in sh6 of Shigella flexneri, sh2 and sh3 of Shigella sonnei individually. The isolated 180 strains were divided into 84 MLVA subtypes, with a resolution ratio D value at 0.967 (95%CI: 0.956 - 0.978). The 130 strains of Shigella flexneri were divided into 63 subtypes, named as TF001-TF063; among which TF001, TF002 and TF 005 were the dominant subtypes, accounting to 17, 16 and 15 strains respectively. The 50 strains of Shigella sonnei were divided into 21 subtypes, named as TS001-TS021; among which TS002 (14 strains) and TS001 (7 strains) were the dominant subtypes.

CONCLUSIONMLVA subtyping method including 10 VNTR loci was preliminarily developed. The MLVA cluster analysis revealed that the subtypes of Shigella strains isolated in Beijing were diverse, and suggested the possibility of multiple-clone source.

Alleles ; Bacterial Typing Techniques ; methods ; China ; DNA, Bacterial ; genetics ; Genotype ; Minisatellite Repeats ; Polymorphism, Genetic ; Shigella ; classification ; genetics ; isolation & purification

ObjectiveTo observe the morphological changes of bone in the progress of chronic fluorosis.MethodsWistar rats were randomly divided into three groups,30 rats in each group:normal control group,experimental group Ⅰ and experimental group Ⅱ according to body weight.Rats in normal control group drank distilled water freely.Experimental group Ⅰ and group Ⅱ drunk distilled water with sodium fluoride preparation of fluorine containing ion 100,150 mg/L solution for six months,respectively.Bone mineral density was detected by X-ray,bone morphological changes were observed under light microscope and bone histomorphometric parameters were calculated using image analysis software.ResultsThe bone mineral density values were different statistically between the three groups after feeding for 2 and 4 months(F =19.79,3.28,all P ＜ 0.05).However no significant difference was found after feeding for 6 months(F =1.80,P ＞ 0.05).The bone mineral density of experimental group Ⅰ (0.20 ± 0.03,0.21 ± 0.03) was significantly higher than that of the normal control group(0.17 ± 0.03,0.20 ± 0.04) after feeding for 2 and 4 months.The bone mineral density of experimental group Ⅱ (0.21 ± 0.02) was lower than that of normal control group(0.22 ± 0.03) after feeding for 6 months.The bone lamella in experimental group Ⅰ was arranged disorderly,the number of osteocytes increased with their nucleus atrophy and the osteoblasts were more than that of control grouo which arranged in layers observed under light microscooy.In exoerimental group Ⅱ,the bone lamella was bent deformation,the number of osteocytes had decreased with their nucleus shrinking or even disappeared and the number of osteoclasts had increased significantly observed under light microscopy.In experimental group Ⅰ,the mean trabecular density [(0.33 ± 0.03)％] increased and the mean trabecular separation,thickness [( 163.57 ± 1.99),(59.26 ± 7.18 ) μm] decreased compared with that of normal control group [(0.31 ± 0.02)％,(186.60 ± 2.90)μm,(86.42 ± 1.48)μm,all P ＜ 0.05].In experimental group Ⅱ,the mean trabecular density[(0.26 ± 0.02)％] decreased,the mean trabecular thickness[(71.42 ± 10.77)μm] reduced compared with that of normal control group[(0.31 ± 0.02)％,(86.42 ± 1.48)μm].ConclusionsExcess fluoride can damage bone tissue.Low doses of fluoride can stimulate osteoblast activity and enhance osteogenesis.The activity of osteoblasts is great than that of osteoclasts.High doses of fluoride can stimulate both osteoblasts and osteoclasts activity,but mainly the activity of osteoclasts,and bone resorption increases.

To sequence and analyze the full-length gene sequence of rabies vaccine virus aG strain. The full-length gene sequence of aG strain was amplified by RT-PCR by 8 fragments,each PCR product was cloned into vector pGEM-T respectively, sequenced and assemblied; The 5' leader sequence was sequenced with method of 5' RACE. The homology between aG and other rabies vaccine virus was analyzed by using DNAstar and Mega4. 0 software. aG strain was 11 925nt(GenBank accession number: JN234411) in length and belonged to the genotype I . The Bioinformatics revealed that the homology showed disparation form different rabies vaccine virus. the full-length gene sequence of rabies vaccine virus aG strain provided a support for perfecting the standard for quality control of virus strains for production of rabies vaccine for human use in China.
Amino Acid Sequence ; Antigens, Viral ; genetics ; immunology ; Base Sequence ; China ; Genome, Viral ; genetics ; Genotype ; Humans ; Molecular Sequence Data ; Phylogeny ; Rabies ; immunology ; prevention & control ; virology ; Rabies Vaccines ; immunology ; Rabies virus ; genetics ; immunology ; Reverse Transcriptase Polymerase Chain Reaction ; Sequence Analysis, DNA ; Sequence Homology, Amino Acid ; Species Specificity