CCK receptor belongs to G-protein-coupled receptor (GPCR) superfamily.Polymorphism of CCK receptors can alter drug affinity and/or biological efficacy, and its genetic differences in amino acid sequences can induce ligand-independent signaling, which in turn can lead to disease. With growing efforts in the field of pharmacogenomics, it is anticipated that polymorphism-induced alterations in drug and/or receptor function will be a focus of increasing concern in the future drug-development project. Study of CCK receptor polymorphism may reveal some universal rules in GPCR superfamily. In this review, the alterations of receptor function and/or drug efficacy resulted from polymorphism in CCK receptors will be discussed in the viewpoint of molecular biology and pharmacogenomics, and some strategies in development of receptor-specific drugs will be put forward.

0.05); but significantly increased cAMP content and PKA activity at high concentration [(10-9~10-5) mol?L-1] (compared with normal control group:P

0.05).But PMA increased and SC-3088 decreased cAMP content and PKA activity in LPS-stimulated rat PIMs(P

AIM To study the role of nitric oxide (NO) and nitric oxide synthase (NOS) inhibitors during the early stage of focal cerebral ischemic injury in rats. METHODS The rat models of middle cerebral artery occlusion were established with the intraluminal suture method. The nonselective NOS inhibitor and selective inducible NOS inhibitor were used for investigating the effects of NO and NOS changes in the focal ischemic brain tissue and their respective roles during the early stage of focal cerebral ischemic injury. RESULTS This study showed that nonselective NOS inhibitors(N G nitro L arginine) aggravated brain damage in the early stage of focal cerebral ischemia and selective iNOS inhibitors (Aminoguanidine )did not significantly improve the brain damage , but could decrease markedly the deterioration of brain damage. CONCLUSION It may be concluded that the NO from defferent cells and types of NOS play unlike roles in the early stage of focal cerebral ischemic injury.

AIM: To investigate the inhibitory effects of cholecystokinin octapeptide(CCK-8) on nuclear factor-?B(NF-?B) activities stimulated by lipopolysaccharide(LPS) by using forskolin,the activator of adenylate cyclase,and PKA inhibitor H-89 in rat pulmonary interstitial macrophages(PIMs).METHODS: PIMs were isolated and purified.EMDA was applied to detect NF-?B activities and Western blotting was used to analyze the I?B-? protein level in rat PIMs.RESULTS: The NF-?B activity was not detected in normal control rat PIMs.The NF-?B activity in LPS-treated rat PIMs was obviously higher than that in control group(P0.05).The NF-?B activity in CCK+LPS group and LPS+Fsk group were obviously lower than that in LPS group(P

Objective:To explore the expressions of miRNAs related to accelerating senescence in serum of the patients with amnestic mild cognitive impairment (aMCI), and to clarify their effects in the pathogenesis of aMIC.Methods:The levels of miRNAs related to accelerating senescence (miR-132, miR-193b, miR-130b, miR-20a, miR-296, miR-329 and miR-206) were measured in the serum of the patients with aMCI (aMCI group,n=66) and healthy controls(control group,n=76) using quantitative real-time PCR(qRT-PCR).The genes targeted by the altered miRNAs were predicted by TargetScan 6.0.DAVID was used to analyze the function of miRNA target genes.The serum levels of brain derived neurotrophic factor (BDNF) and silent in formation regulator 1(SIRT1) were measured by enzyme-linked immunosorbent assay (ELISA) method.Results:The expression levels of miR-206 and miR-132 in serum of the patients in aMCI group were significantly higher than those in control group (P<0.05).BDNF and SIRT1 were both target genes of miR-206 and miR-132.The levels of BDNF (29.50 μg·L-1± 3.13 μg·L-1) and SIRT1 (1.86 μg·L-1± 0.25 μg·L-1) in serum of the patients in aMCI group were both obviously lower than those in control group (BDNF: 32.29 μg·L-1±3.66 μg·L-1;SIRT1: 2.10 μg·L-1± 0.29 μg·L-1, P<0.05).Conclusion:The expression levels of miR-206 and miR-132 in serum of the aMCI patients are significantly up-regulated.Both of them might be involved in the pathogenesis of aMCI through inhibiting the BDNF and SIRT1 expressions.

Objective To investigate the effect of acetyl-L-carnitine (ALC) preconditioning on the PC12 cell apoptosis induced by oxygen-glucose deprivation.Methods PC12 cells were seeded in 96-well plates and randomly divided into 5 groups ( n =6 each):control group (group C),cell injury group (group Ⅰ) and preconditioning with different concentrations of ALC groups (groups A1-3 ).In group C,the cells were incubated with DMEM liquid culture medium containing glucose 0.5 g/L for 3 h.In groups Ⅰ and A1-3 the cells were incubated with DMEM liquid culture medium containing sodium hydrosulfite (Na2S2O4) 3 mmol/L and glucose 0.5 g/L for 3 h,and in addition the cells were pre-incubated with ALC 0.2,0.4 and 0.6 mmol/L for 24 h in groups A1-3 respectively.Cell viability was evaluated by MTF assay,while the apoptosis in cells was detected using TUNEL.The activities of ATPase and SOD and MDA content were also detected.Results Oxygen-glucose deprivation significantly increased the number of apoptotic cells and the content of MDA,and decreased the cell viability and activities of SOD and ATPase in group Ⅰ compared with group C ( P ＜ 0.05).Preconditioning with ALC significantly increased the cell viability and the activities of SOD and ATPaes,and decreased the number of apoptotic cells and the content of MDA in groups A1-3 compared with group Ⅰ ( P ＜ 0.05).Conclusion ALC preconditioning can attenuate PC12 cell injury induced by oxygen-glucose deprivation through inhibition of apoptosis in cells.

AIM: To investigate the binding characteristics of cholecystokinin receptors in rat pulmonary interstitial macrophages (PIMs). METHODS: The PIMs were isolated from rat lung tissues, purified using the collagenase digestion method combined with alveolar lavage and pulmonary vessel perfusion. The PIM membrane was obtained by supercentrifuge. Receptors for CCK in PIMs were examined using [~3H] labeled CCK-8S as ligand. The specificity of [~3H]-CCK-8S binding to PIMs membrane and the subtypes of CCK receptors were determined by competitive inhibition experiments with CCK-8S, CCK-A and CCK-B receptors selective antagonists (CR1409 and CR2945). The effects of time and incubation temperature on the specific binding were also observed. RESULTS: The specific binding of [~3H]-CCK-8S was not detected in normal rat PIMs, but was detected in the rat administrated with LPS for 48 h. The capacity of ligand-receptor binding was dependent on the incubation temperature and time. Scatchard analysis of the saturation curves suggested that the presence of CCK receptors with high affinity [Kd=(0.68?0.28)mmol/L] and low binding capacity [Bmax=(32.50?2.70) pmol?g~(-1) protein] in PIMs. By means of competitive inhibition studies, the specific binding of [~3H]-CCK-8S to rat PIMs was inhibited by unlabelled CCK-8S [IC_(50)=(3.20?1.13) nmol/L], CCK-AR specific antagonist CR 1 409 [IC_(50)=(0.19?0.06)?mol/L] and CCK-BR specific antagonist CR 2945[IC_(50)=(2.30?0.80)nmol/L]. CONCLUSION: These results suggest the presence of two subtypes of CCK-AR and CCK-BR and provide a structural basis for CCK to play a pivotal role in PIMs.

Objective: To investigate influences of high-voltage electrical burns on microcirculation perfusion on serosal surface of small intestine of rats and the interventional effects of pentoxifylline (PTX). Methods: Totally 180 SD rats were divided into sham injury group, simple electrical burn group, and treatment group according to the random number table, with 60 rats in each group. The electrical current was applied to the outside proximal part of left forelimb of rats and exited from the outside proximal part of right hind limb of rats. Rats in simple electrical burn group and treatment group were inflicted with high-voltage electrical burn wounds of 1cm×1cm at current entrances and exits, with the voltage regulator and experimental transformer. Rats in sham injury group were sham injured through connecting the same equipments without electricity. At 2 min post injury, rats in sham injury group and simple electrical burn group were intraperitoneally injected with 2 mL normal saline, and rats in treatment group were injected with 2 mL PTX injection (50 mg/mL). At 15 min before injury and 5 min, 1 h, 2 h, 4 h, and 8 h post injury, 10 rats in each group were selected to collect blood of heart respectively. Serum were separated from the blood to determine the level of soluble vascular cell adhesion molecule-1(sVCAM-1) with enzyme-linked immunosorbent assay method. The number of adhesional leukocyte in mesenteric venule of rats was determined with Bradford variable projection microscope system. The microcirculation perfusion on serosal surface of small intestine of rats was detected with laser Doppler perfusion imager. Data were processed with analysis of variance of factorial design and LSD test. Results: (1) At 5 min, 1 h, 2 h, 4 h, 8 h post injury, the serum content of sVCAM-1 in rats of simple electrical burn group were (8 502±1 158), (11 793±3 310), (9 960±2 146), (9 708±1 429), (7 292±1 386) ng/mL respectively, higher than that in sham injury group and treatment group [ (1 897±946), (1 882±940), (1 882±938), (1 888±946), (1 884±942) ng/mL, and (6 840±1 558), (6 742±2 465), (5 625±2 593), (2 373±1 463), (5 187±2 797) ng/mL, respectively, with P values below 0.001]. The serum content of sVCAM-1 in rats of sham injury group and treatment group at all time points post injury, except 4 h post injury of treatment group, was higher than that of the same group at 15 min before injury (with P values below 0.001). (2) At all time points post injury, the number of adhesional leukocyte in mesenteric venule of rats in simple electrical burn group was higher than that in sham injury group and treatment group (with P values below 0.001). The number of adhesional leukocyte in mesenteric venule of rats in simple electrical burn group and treatment group at all time points post injury was higher than that of the same group at 15 min before injury (with P values below 0.001). (3) At all time points post injury, the microcirculation perfusion on serosal surface of small intestine of rats in simple electrical burn group was lower than that in sham injury group and treatment group (with P values below 0.001). The microcirculation perfusion on serosal surface of small intestine of rats in simple electrical burn group and treatment group at all time points post injury was lower than that of the same group at 15 min before injury (with P values below 0.001). Conclusions High-voltage electrical burns can increase the serum content of sVCAM-1, the number of adhesional leukocyte in mesenteric venule, and reduce microcirculation perfusion on serosal surface of small intestine of rats. PTX can inhibit secretion of serum sVCAM-1, reduce the number of adhensional leukocyte in mesenteric venule to alleviate microcirculation disturbance caused by high-voltage electrical burns.

Objective:To explore the clinical effect of repair of distal thumb degloving injury with B-shaped first palmar dorsal neurocutaneous vascular flap.Methods:The clinical data included 15 patients with distal thumb degloving injury received in Yongkang Orthopedic Hospital from March 2015 to June 2018. These patients included 10 males and 5 females, aged between 24 and 61 years. For the injury, 7 cases were beyond the interphalangeal joint, 8 cases were beyond the nail root. The length of the distal segment of degloving finger was 1.8 to 2.3 cm, and the skin and soft tissue defect ranged from 1.8 cm × 4.6 cm to 2.3 cm × 5.6 cm. The distal thumb degloving injury was repaired with B-shaped first palmar dorsal neurocutaneous vascular flap. The radial dorsal metacarpal nerve of the first metacarpal was anastomosed with the ulnar proper digital nerve stump. And full-thickness skin graft transplantation was performed in donor area. After the operation, the shape and function of the thumb were followed up. The sensory function of the skin was determined by British Medical Research Association Sensory Function Evaluation Standard, and the function of the thumb was evaluated with reference to the total active movement (TAM) of fingers of the Chinese Medical Association Hand Surgery Branch.Results:The flap area was 2.0 cm × 5.0 cm-2.5 cm × 6.0 cm, and all the flaps were survived. Follow-up period was 5-18 months after the operation, with an average of 10 months. The flap at the thumb repair site was soft, wear-resistant, non-bloated, no obvious pigmentation. Its protective sensation was restored. The two-point discrimination of the flap reached 8-11 mm, with an average of 9.3 mm, basically restoring the original shape and function of the thumb. There were 13 cases reaching the S3 + flap sensory function, 2 cases reaching S3. The thumb function was evaluated as excellent for 9 cases, and good for 6 cases. There were no complications such as scar contracture and hypersensitivity in the donor area. Conclusions:The repair of distal thumb degloving injury with B-shaped first palmar dorsal neurocutaneous vascular flap can complete skin coverage and sensory reconstruction, with satisfactory postoperative effect.