ABSTRACT
Most α2-AR agonists derived from dexme-detomidine have few structure differences between them and have no selectivity for α2A/2B-AR or Gi/Gs,that can lead to the side effect of drugs.To get novel and potent α2A-AR agonists,we built the homology model for human α 2A-AR and α2B-AR to find α2A-AR agonists with higher selectivity.Compound P300-2342 and its 3 analogs sig-nificantly decreased the locomotor activity of mice(P＜0.05).Furthermore,P300-2342 and its 3 analogs inhibited the binding of[3H]rauwolscine to α 2A-AR and α 2B-AR respectively.In α2A-AR-HEK293 cells,P300-2342 decre-ased forskolinstimulatedcAMPpruductionwithoutincreas-ing cAMP pruduction,that indicated the P300-2342 acti-vating α2A-AR coupling with Gαi/o pathway without Gαs coupling.P300-2342 had no agonistic and antagonistic activities on α 2B-AR.Similar results were shown in 3 analogs of P300-2342.The docking results showed that P300-2342 formed the π-hydrogen bonds with Y394,V114 of α2A-AR,and with V93 of α2B-AR.3 analogs of P300-2342 formed several π-hydrogen bonds with V114,Y196,F390 of α 2A-AR and with V93 of α 2B-AR.We believe that these molecules can serve as leads for fur-ther optimization of α2A-AR agonists with potentially few side effects.
ABSTRACT
Platelet-rich plasma (PRP) is a kind of autologous blood product. It is a platelet concentrate extracted from autologous blood through centrifugation or apheresis process. It is generally believed that the platelet concentration in PRP should be 4-8 times of the platelet count in the whole blood. Platelets with high concentration can release a variety of growth factors and media after activation, which is conducive to tissue repair and regeneration. PRP has been used in regenerative medicine for more than 30 years, and has achieved good results. In recent years, it has also been widely used in facial aesthetics, involving acne, skin aging, hair loss, chloasma and other fields. In this review, we are not only emphasized the preparation and use of PRP, but also outlined the application progress of PRP in facial aesthetics.
ABSTRACT
Objective To compare the effect of two different types of cardiopulmonary resuscitation (CPR)in cardiac arrest.Methods 150 patients with cardiac arrest were selected.The patients were divided into two groups according to the random number table method,each group in 75cases.The patients in the control group were treated with CPR.The patients in the observation group were treated with CPR machine.The body temperature,hemoglobin concentration,hematocrit,arterial blood gas analysis and resuscitation were compared between the two groups after 10min and 30min.Results There were no statistically significant differences in body temperature,hemoglobin and hematocrit between the control group and the observation group at 10min and 30min after CPR (t10min =1.44,2.01,1.23,t30min =1.69,1.81,1.02,all P ＞ 0.05).There were no statistically significant differences in PaCO2 between the two groups at 10 min and 30 min after resuscitation (t =1.54,1.02,all P ＞ 0.05).The arterial blood pH[(7.02 ±0.14)],PaO2 [(16.29 ± 4.38) kPa],HCO3 [(5.66 ± 1.73) kPa] and SaO2 [(0.84 ± 0.05) ％] of the control group recovered 30 min were significantly lower than recovered 10 min (t =7.14,6.55,6.20,7.03,all P ＜ 0.05).The arterial blood pH[(7.11 ± 0.1)],PaO2 [(18.36 ± 4.55) kPa],HCO3 [(6.34 ± 2.15) kPa],SaO2 [(0.86 ±0.04) ％] of the observation group recovered 30 min were significantly lower than recovered 10 min (t =6.75,6.21,6.01,6.60,all P ＜0.05).The arterial blood pH,PaO2,HCO3 and SaO2 of the observation group were significantly higher than those in the control group at 10 min and 30 min,the differences were statistically significant (t10min =6.03,7.34,7.88,6.10,t30min =6.21,8.20,7.10,6.11,all P ＜ 0.05).The effective rate of CPR in the observation group was 69.33％,which was significantly higher than 46.67％ in the control group,the difference was statistically significant (x2 =9.34,P ＜ 0.05).Conclusion Compared with artificial heart and lung resuscitation,CPR machine is more effective for patients with heartbeat respiratory arrest.It is more effective in cycling support and can improve the efficacy of CPR and is worthy of clinical application.
ABSTRACT
OBJECTIVE To establish a new cell line that can stably express humanα2A-adrenoceptor (α2A- AR). METHODS Recombinant plasmid of α2A- AR with hygromycin B (Hygro) resistance (pcDNA3.1/Hygro-HA-α2A-AR)was stably transfected into Chinese hamster ovary(CHO)cells which had expressed protein kinase A catalytic subunits(PKAcat) with labeling of enhanced green fluorescent protein(EGFP)by a Lipofectamine based method. A single positive clone expressingα2A-AR was selected through cultivation in the presence of 200 mg · L-1 hygromycin B followed by PKA redistribution assay. The transcriptional expression ofα2A-AR was detected by quantitative real-time PCR(qRT-PCR). Time-resolved fluorescence resonance energy transfer immunoassay was used to identify the function of inhibiting cAMP accumulation of α2A-AR. RESULTS The CHO-PKAcat-α2A-AR cell line No.7 exhibited stable response in PKA redistribution assay. qRT-PCR analysis demonstrated that the high expression ofα2A-AR in the cell line remained stable after a few generations compared with CHO-PKAcat-EGFP cells (P<0.01). The cAMP accumulation caused by forskolin was significantly inhibited by α2A-AR agonist in CHO-PKAcat-α2A-AR cells(P<0.01). CONCLUSION CHO-PKAcat-α2A-AR cell line is constructed successfully, which provides an effective model for drug screening and studies of mechanisms.
ABSTRACT
This study investigates whether kappa-opioid receptor and ORL1 receptor may interact to form a heterodimer. In immunofluorescence and co-immunoprecipitation experiments, differentially epitope-tagged receptors, colocalization and heterodimerization of kappa-opioid receptor and ORL1 receptor were used and examined in primary culturing rat neurons, Chinese hamster ovary (CHO) or human embryonic kidney 293 (HEK293) cells. The results show that fluorescence of both kappa-opioid receptor and ORL1 receptor were overlapping in primary culturing hippocampal and cortical neurons. Similarly in co-expressing CHO or HEK293 cells, HA-KOR and Myc-ORL1 were almost exclusively confined to the membranes, revealing extensive colocalization. When Flag-KOR and Myc-ORL1 were co-expressing in CHO cells, heterodimerization was identified to have the ability to co-immunoprecipitate ORL1-receptors with kappa-opioid receptor and vice versa. In the current study, further evidence was provided for the direct interaction of two subtypes of opioid receptors, kappa-opioid receptor and ORL1-receptor, to form the heterodimerization. The finding represents the novel pharmacological mechanism for modulation of opioid receptor function as well as diversity of G protein-coupled receptors.
ABSTRACT
Mental retardation is defined by significant limitations in intellectual function and adaptive behavior that occur before 18 years of age. Many chromosomal diseases come with mental retardation. We reported two Chinese families with partial trisomy 9p and other chromosome partial monosomy, clinical features of mental retardation and mild facial and pinkie anomalies. In the family 1, we showed that the proband carried a trisomy 9p21.3→pter and monosomy 21q22.3→qter by using fluorescence in situ hybridization analysis. Molecular genetic analysis defined the precise breakpoint on chromosome 9p between markers D9S1846 and D9S171, an interval of about 2.9 Mb on 9p21.3, and the breakpoint on chromosome 21q between markers D21S1897 and D21S1446, a region of about 1.5 Mb on 21q22.3. In the family 2, a patient with trisomy 9p21.3→pter and monosomy 5p15.33→pter, and a de novo maternal balanced translocation between chromosomes 5 and 9 was identified in his mother. Cytogenetic and molecular genetic analysis defined the precise breakpoints on chromosome 9p21.3 and chromosome 5p15.33. Further clinical investigation found that any individual had no refractoriness eczema disease except the proband in this family. These results further implicate that trisomy 9p is associated with mental retardation, and that there may be key gene duplication on chromosome 9p21.3→9pter responsible for mental retardation and mild facial anomaly. This result has been applied successfully in prenatal diagnosis of the second family.