HMGB1 and inflammatory cytokines in experimental acute lung injury induced in rabbits / [HMGB1 e citocinas inflamatórias em lesão pulmonar aguda experimental induzida em coelhos]

The aim of this work was to measure HMGB1, TNF-alpha, and IL-8 in bronchoalveolar lavage (BAL), serum and TLR2 and TLR4mRNA expression in lung tissue of rabbits with two grades of acute lung injury (ALI). The animals were randomly assigned to groups with severe (S) and mild/moderate (MM) ALI, induced with warm saline, and a control group. HMGB1, TNF-alpha, IL-8, TLR2mRNA and TLR4mRNA were measured after ALI induction. The results showed increased levels of IL-8, TNF-alpha, HMGB1 and TLR4mRNA in the ALI groups. HMGB1, IL-8 and TNF-alpha concentrations in BAL were higher in S compared MM. Increased TLR4mRNA was observed in S and MM versus control. The results suggest an early participation of HMGB1 in ALI together with IL-8 and TNF-alpha and association with severity. TLR4 has early expression and role in ALI pathophysiology but is not associated with severity.(AU)

O objetivo deste trabalho é determinar os níveis de HMGB1, TNF-alfa e IL-8 no lavado broncoalveolar (BAL), bem como quantificar a expressão sérica de TLR2 e TLR4 mRNA em tecido pulmonar de coelhos com dois graus de lesão pulmonar aguda (LPA). Os animais foram distribuídos aleatoriamente em grupos com LPA grave (S) e leve / moderada (MM), induzidas com solução salina morna, e um grupo controle. HMGB1, TNF-alfa, IL-8, TLR2mRNA e TLR4mRNA foram medidos após a indução de LPA e quatro horas de ventilação mecânica. Os resultados mostraram níveis aumentados de IL-8, TNF-alfa, HMGB1 e TLR4mRNA nos grupos com LPA. As concentrações de HMGB1, IL-8 e TNF-alfa no LBA foram maiores no S comparado ao MM. Aumento de TLR4mRNA foi observado em S e MM versus controle. Os resultados sugerem uma participação precoce da HMGB1 na LPA em conjunto com IL-8 e TNF-alfa e associação com a gravidade da LPA. O TLR4 foi expresso na ALI e possivelmente possui papel precoce na fisiopatologia da LPA, mas sem associação com a gravidade.(AU)

Coronary artery calcium is associated with lpa gene variant RS7765803-C in Mexican mestizo population The GEA Project

ABSTRACT Background: Lipoprotein(a) [Lp(a)] levels are genetically determined; high levels are a risk factor for coronary disease, although their association with coronary artery calcium (CAC) is controversial. Objective: The objective of the study was to assess the association of LPA gene polymorphisms with CAC in a Mexican Mestizo population. Methods: We included 1594 subjects 35-70 years old. Six polymorphisms of the LPA gene were analyzed. CAC score was determined by tomography and Lp(a) serum levels by immunonephelometry. The association of LPA polymorphism with CAC and Lp(a) was evaluated by logistic regression. Results: The prevalence of Lp(a) ≥30 mg/dL was 10%, and of CAC >0 was 26.9%. Three polymorphisms were associated with high Lp(a) levels: rs10455872-G (p = 0.013), rs6907156-T (p = 0.021), and rs7765803-C (p = 0.001). Homozygotes (CC) for the rs7765803 variant compared with the G allele (CG + GG) carriers had higher Lp(a) levels (8.9 [3.3-23.9] vs. 4.9 [2.3-11.2] mg/dL; p = 0.015) and higher prevalence of CAC >0 (36.5% vs. 26.3%, p = 0.045) and were associated with CAC > 0 (odds ratio = 1.7, 95% confidence interval: 1.06-2.7; p < 0.026). The other polymorphisms were not associated with CAC. Conclusions: This is the first study to demonstrate in a Mexican Mestizo population that carriers of the rs7765803-C allele of LPA gene have 2.6 times greater risk for high Lp(a) values and 1.7 times higher risk for coronary artery disease.

Expression of YAP, LPA and TAZ in head and neck squamous cell carcinoma and its correlation with clinicopathological data / 实用医学杂志

Objective To investigate the expression of YAP,LPA and TAZ in head and neck squamous cell carcinoma and its clinical significance.Methods Selective collection of Ya'an People's Hospital pathology department from January 2010 to December 2016,the surgical resection of the pathological tissue paraffin specimens amounted to 136 cases,including the normal tissue of head and neck squamous cell carcinoma 37 cases,head and neck benign tumor-like tissue 35 cases,head and neck squamous cell carcinoma 64 cases,all specimens without chemotherapy history,The relationship between the expression of LPA,YAP and TAZ in various tissues by immunohistochemistry and real-time quantitative PCR assay and its clinical correlative parameters.Results The expression of LPA mRNA in normal tissues,benign neoplasia tissues and squamous carcinoma tissues of the head and neck squamous cell carcinoma was similar (P ＞ 0.05).The expression of YAP mRNA in squamous cell carcinoma tissues was higher than that in the adjacent tissues and tumor tissues (P ＜ 0.05).TAZ mRNA was low expression in the three tissues of the head and neck,but the expression of squamous cell carcinoma was significantly higher than that of benign tumor tissues and adjacent normal tissues (P ＜ 0.05).The expression of YAP and TAZ protein was significantly higher than that in the tissues of normal tissues and benign tumor tissues (P ＜ 0.05).The expression of YAP in squamous cell carcinoma was significantly higher than the control group (P ＜ 0.05).The expression of TAZ was low differentiation in tumor,tumor ＞3.0 cm,lymph node positive and Ⅲ-Ⅳ period were higher than the control group (P ＜ 0.05).Condusions The expression of YAP and TAZ in head and neck squamous cell carcinoma was closely related to tumor staging,differentiation degree and lymph node metastasis,while the expression of LPA showed no significant difference and correlation.

Design,synthesis and preliminary anti-radiation activityof novel LPA2 receptor agonists / 国际药学研究杂志

Objective To design and synthesize novel G protein-coupled lysophosphatidic acid 2(LPA2)receptor agonists with anti-radiation activity. Methods Nine new LPA2 receptor agonists(Ⅰ2-Ⅰ5 andⅡ1-Ⅱ5)were designed and synthesized using DBIBB as the lead compound. The anti-radiation activity was assayed by the MTS method using the human umbilical vein endothelial cells(HUVEC)irradiated with 8.0 Gy 60Coγray. Results and Conclusion Nine target compounds notreported in the literature were synthesized and their structures were confirmed by 1H NMR and MS. The results showed thatⅠ4 andⅡ1 have obvious anti-radiation ac-tivity,indicating that this kind of compounds is worth further studying.

Effect of hepatitis B virus X protein on autotaxin expression and its significance / 实用医学杂志

Objective To explore the effect of hepatitis B virus (HBV) X protein (HBx) on autotaxin (ATX) expression and its significance. Methods The recombinant eukaryotic expression vector of HBx ,pcD-NA3.1(+)-HBx,and the recombinant luciferase reporter gene vector of ATX promoter,pGL3-ATX,were con-structed and used to co-transfect HepG2 cells to examine the effect of HBx on the activity of ATX promoter. The sta-ble cell expressing HBx,HepG2.HBx,was constructed,and Western blot(WB)was used to detect the effect of HBx on ATX expression. Results The luciferase activity of pcDNA3.1(+)-HBx and pGL3-ATX group was 1.47 times as that of the empty vector cDNA3.1(+)and pGL3-ATX group(P<0.000). WB detection showed that the expression of ATX protein was increased in HepG2.HBx cells,and 1.75 times as that of HepG2 cells(P<0.05). Conclusion HBx can activate ATX promoter and up-regulate ATX expression ,thus suggests that HBV infection might enhance ATX/LPA signaling.

Association between the serum CysC,lipoprotein(a) and urinary microalbumin/creatinine ratio among elderly type 2 dibetic patients / 国际检验医学杂志

Objective To analyze the relationship between the serum CysC,lipoprotein(a) [Lp(a)] and the urinary microalbumin/creatinine ratio in elderly type 2 dibetic (T2CM) patients.Methods A total of 102 elderly patients with T2CM who were treated in our hospital from December 2014 to December 2015 were selected.The patients were divided into diabetic nephropathy(DN) group(mALB≥20 μg/min,48 cases)and non-diabetic nephropathy(NDN) group (mALB<20 μg/min,54 cases) according the levels of urinary mALB,while 30 cases of healthy controls were selected from physical examination center.The biochemical indexes,CysC,Lp(a) and UACR were detected among all cases.The correlation between indexes and UACR was analyzed by Pearson correlation analysis,risk factors for UACR among DN patients were analyzed by Logistic regression analysis.Results There were significant differences in levels of low density lipoprotein cholesterol(LDL-C),Lp(a),urea,creatinine,fasting blood glucose(FBG),glycosylated hemoglobin(HbA1c),Cysc,and UACR among these groups (P<0.05).No correlation between CysC、Lp(a) and UACR was found in normal-control group and non-diabetic nephropathy group.In diabetic nephropathy group,there was a positive correlation between CysC,Lp(a) and UACR(r=0.658,P<0.01;r=0.525,P<0.05).The Logistic regression analysis showed that diabetes duration,CysC,Lp(a) were independent risk factors for UACR(P<0.05).Conclusion In patients with diabetic nephropathy,CysC,Lp(a) are positively correlated with UACR,and CysC is a sensitive index that reflect early renal damage in T2DM patients.Lp(a) level is one of the independent risk factors for UACR,which can reveal the kidney damage in DN patients.

Role of TAZ in Lysophosphatidic Acid-Induced Migration and Proliferation of Human Adipose-Derived Mesenchymal Stem Cells

Transcriptional co-activator with a PDZ-binding motif (TAZ) is an important factor in lysophosphatidic acid (LPA)-induced promotion of migration and proliferation of human mesenchymal stem cells (MSCs). The expression of TAZ significantly increased at 6 h after LPA treatment, and TAZ knockdown inhibited the LPA-induced migration and proliferation of MSCs. In addition, embryonic fibroblasts from TAZ knockout mice exhibited the reduction in LPA-induced migration and proliferation. The LPA1 receptor inhibitor Ki16425 blocked LPA responses in MSCs. Although TAZ knockdown or knockout did not reduce LPA-induced phosphorylation of ERK and AKT, the MEK inhibitor U0126 or the ROCK inhibitor Y27632 blocked LPA-induced TAZ expression along with the reduction in the proliferation and migration of MSCs. Our data suggest that TAZ is an important mediator of LPA signaling in MSCs in the downstream of MEK and ROCK signaling.

Role of TAZ in Lysophosphatidic Acid-Induced Migration and Proliferation of Human Adipose-Derived Mesenchymal Stem Cells

Transcriptional co-activator with a PDZ-binding motif (TAZ) is an important factor in lysophosphatidic acid (LPA)-induced promotion of migration and proliferation of human mesenchymal stem cells (MSCs). The expression of TAZ significantly increased at 6 h after LPA treatment, and TAZ knockdown inhibited the LPA-induced migration and proliferation of MSCs. In addition, embryonic fibroblasts from TAZ knockout mice exhibited the reduction in LPA-induced migration and proliferation. The LPA1 receptor inhibitor Ki16425 blocked LPA responses in MSCs. Although TAZ knockdown or knockout did not reduce LPA-induced phosphorylation of ERK and AKT, the MEK inhibitor U0126 or the ROCK inhibitor Y27632 blocked LPA-induced TAZ expression along with the reduction in the proliferation and migration of MSCs. Our data suggest that TAZ is an important mediator of LPA signaling in MSCs in the downstream of MEK and ROCK signaling.

Calcium Signaling of Lysophosphatidylethanolamine through LPA1 in Human SH-SY5Y Neuroblastoma Cells

Lysophosphatidylethanolamine (LPE), a lyso-type metabolite of phosphatidylethanolamine, has been reported to be an intercellular signaling molecule. LPE mobilizes intracellular Ca²⁺ through G-protein-coupled receptor (GPCR) in some cells types. However, GPCRs for lysophosphatidic acid (LPA) were not implicated in the LPE-mediated activities in LPA GPCR overexpression systems or in SK-OV3 ovarian cancer cells. In the present study, in human SH-SY5Y neuroblastoma cells, experiments with LPA₁ antagonists showed LPE induced intracellular Ca²⁺ increases in an LPA₁ GPCR-dependent manner. Furthermore, LPE increased intracellular Ca²⁺ through pertussis-sensitive G proteins, edelfosine-sensitive-phospholipase C, 2-APB-sensitive IP₃ receptors, Ca²⁺ release from intracellular Ca²⁺ stores, and subsequent Ca²⁺ influx across plasma membranes, and LPA acted on LPA₁ and LPA₂ receptors to induce Ca²⁺ response in a 2-APB-sensitive and insensitive manner. These findings suggest novel involvements for LPE and LPA in calcium signaling in human SH-SY5Y neuroblastoma cells.

Performance Verification of LP(a)Reagents in Clinical Laboratory / 现代检验医学杂志

Objective To validate the analytical performance of four LP(a)reagents with Immunoturbidimetry method used on the automatic biochemistry analyzer for preliminary clinical application.Methods The performance of four LP(a)reagents (labeled as A,B,C,D)with method from RANDOX,Zhejiang Kuake Co.,Beijing Leadman Co.and Beijing Jiuqiang Co.on Olympus AU5800 automatic biochemistry analyzer were assessed.The precision,linearity range,accuracy,disturbance (vita-min C,bilirubin,hemoglobin,TG)were assessed.Results The within-run CVs of the four reagents (A,B,C and D)were 0.64%~1.18%,3.59%~4.75%,1.33%~3.05% and 1.43%~2.01% respectively.The between-run CVs in A,B,C and D were 1.04%~1.7%,3.81%~4.93%,2.16%~4.76% and 2.33%~3.21% respectively,lower than the stated.The lin-earity range was 82~923 mg/L (r2 =0.997),130~935 mg/L (r 2 =0.996 4),120~1025 mg/L (r 2 =0.992 1)and 117~943 mg/L (r2 =0.999 5)in the four reagents,which demonstrated a sound linear correlation.For interference tests,no re-markable interferences (<±10%)of reagent A and reagent D were detected when Vitamin C≤10 mg/dl,hemoglobin≤200 mg/dl,bilirubin≤40 mg/dl and TG≤500 mg/dl.Interference of reagent B was found when VC≥5 mg/dl,TG≥250 mg/dl and when TG≥250 mg/dl reagent C was interfered significantly.The four LP(a)reagents were used to detect the lipid con-trol,and the deviations of the target value were - 8.07%,1.34%,- 8.05% and 7.38% respectively.Conclusion When used in automatic biochemical analyzer,the four LP(a)reagents showed high precision.The four reagents are all able to meet clinical test requirements,nevertheless,anti-interference capability were different.

Effect of lysophosphatidic acid on hepatocellular carcinoma cell migration and its involved mechanisms / 医用生物力学

Objective To investigate the effect of lysophosphatidic acid (LPA) on migration of hepatocellular carcinoma MHCC97H cells and its involved mechanisms. Methods Transwell was utilized to investigate the impact of LPA on cell migration of MHCC97H cells. Furthermore, the role of ROCK in the migration of MHCC97H cells through Y-27632 (a specific inhibitor of ROCK). Then, the expression of F-actin was observed with immunofluorescence staining and Western blotting. Atomic force microscopy (AFM) was employed to investigate elastic modulus of MHCC97H cells. Results LPA significantly promoted the migration of MHCC97H cells, while Y-27632 significantly blocked the migration of MHCC97H induced by LPA. Moreover, LPA up-regulated the expression of F-actin and decreased the elastic modulus of MHCC97H cells. Conclusions LPA promotes MHCC97H cell migration through decreasing the cell stiffness via ROCK/F-actin.

Clinical Observation of Atorvastatin Calcium Combined with Metoprolol in the Treatment of Chronic Conges-tive Heart Failure / 中国药房

OBJECTIVE:To observe the efficacy and safety of atorvastatin calcium combined with metoprolol in the treatment of chronic congestive heart failure (CHF). METHODS:207 CHF patients were randomly divided into control group (102 cases) and observation group (105 cases). Control group received cardiac,diuretic,vasodilating and oxygen inhalation,Metoprolol tar-trate tablet with initial dose of 6.25 mg,2-3 times a day,then increased 6.25-12.5 mg based on the improvement,2-3 times a day. Observation group additionally received 80 mg Atorvastatin tablet,twice a day. The treatment course for both groups was 16 w. Clinical efficacy,cardiac functions [left ventricular ejection fraction(LVEF),left ventricular end systolic diameter(LVESD),mi-tral early diastolic and late diastolic peak flow velocity ratio(E/A)],blood lipids [lipoprotein(a)Lp(a),triglyceride(TG),total cholesterol(TC)] levels before and after treatment,and the incidence of adverse reactions in 2 groups were observed. RESULTS:The total effective rate in observation group was significantly higher than control group,the difference was statistically significant (P0.05). Af-ter treatment,the LVEF and E/A in 2 groups were significantly higher than before,and observation group was higher than control group,LVESD,Lp(a),TG and TC were significantly lower than before,and observation group was lower than control group,the differences were statistically significant (P0.05). CONCLUSIONS:Based on conventional treatment,the efficacy of atorvastatin calcium combined with metoprolol is su-perior to metoprolol in the treatment of CHF,with better safety.

Gintonin facilitates catecholamine secretion from the perfused adrenal medulla

The present study was designed to investigate the characteristics of gintonin, one of components isolated from Korean Ginseng on secretion of catecholamines (CA) from the isolated perfused model of rat adrenal gland and to clarify its mechanism of action. Gintonin (1 to 30 µg/ml), perfused into an adrenal vein, markedly increased the CA secretion from the perfused rat adrenal medulla in a dose-dependent fashion. The gintonin-evoked CA secretion was greatly inhibited in the presence of chlorisondamine (1 µM, an autonomic ganglionic bloker), pirenzepine (2 µM, a muscarinic M₁ receptor antagonist), Ki14625 (10 µM, an LPA₁/₃ receptor antagonist), amiloride (1 mM, an inhibitor of Na⁺/Ca²⁺ exchanger), a nicardipine (1 µM, a voltage-dependent Ca²⁺ channel blocker), TMB-8 (1 µM, an intracellular Ca²⁺ antagonist), and perfusion of Ca²⁺-free Krebs solution with 5mM EGTA (a Ca²⁺chelater), while was not affected by sodium nitroprusside (100 µM, a nitrosovasodialtor). Interestingly, LPA (0.3~3 µM, an LPA receptor agonist) also dose-dependently enhanced the CA secretion from the adrenal medulla, but this facilitatory effect of LPA was greatly inhibited in the presence of Ki 14625 (10 µM). Moreover, acetylcholine (AC)-evoked CA secretion was greatly potentiated during the perfusion of gintonin (3 µg/ml). Taken together, these results demonstrate the first evidence that gintonin increases the CA secretion from the perfused rat adrenal medulla in a dose-dependent fashion. This facilitatory effect of gintonin seems to be associated with activation of LPA- and cholinergic-receptors, which are relevant to the cytoplasmic Ca²⁺ increase by stimulation of the Ca²⁺ influx as well as by the inhibition of Ca²⁺ uptake into the cytoplasmic Ca²⁺ stores, without the increased nitric oxide (NO). Based on these results, it is thought that gintonin, one of ginseng components, can elevate the CA secretion from adrenal medulla by regulating the Ca²⁺ mobilization for exocytosis, suggesting facilitation of cardiovascular system. Also, these findings show that gintonin might be at least one of ginseng-induced hypertensive components.

Effect of high dose metformin on serum HE4, LPA and regulatory T cells in patients with ovarian cancer / 中国生化药物杂志

Objective To analysis the effect of high dose metformin on serum HE4, LPA and regulatory T cells in patients with ovarian cancer.Methods 80 cases of unilateral ovarian cancer patients were given surgery and conventional chemotherapy ,were divided into four groups according to single metformin dose: (group A:0.25g each time, B group:0.25g each time, group C:0.25g each time; group D: conventional treatment only) and three times a day oral administration of metformin and two weeks in a row , before and after the treatment of detection each serum HE4, LPA, transformation growth factor beta 1 (TGF -beta 1), interleukin -10 (IL-10) content, and CD4 +CD25 +CD127 regulating T cell percentage.ResuIts Compared with B, C, and D group, the efficacy of patients in group A was better, as follows: Serum HE4 content decreased significantly ( P<0.05 ); serum LPA content decreased significantly ( P<0.05 ); blood CD4 +CD25 +CD127 regulatory T cell percentage decreased significantly ( P<0.05 ); serum TGF beta 1, IL-10 content decreased significantly ( P<0.05 ) .The results were statistically significant .ConcIusion High dose of metformin can reduce serum HE4 , LPA content, reduce the adjusting the percentage of T cells and related cytokines in patients with ovarian cancer , and play a positive role in inhibit cancer cell proliferation and invasion .

Action and Signaling of Lysophosphatidylethanolamine in MDA-MB-231 Breast Cancer Cells

Previously, we reported that lysophosphatidylethanolamine (LPE), a lyso-type metabolite of phosphatidylethanolamine, can increase intracellular Ca2+ ([Ca2+]i) via type 1 lysophosphatidic acid (LPA) receptor (LPA1) and CD97, an adhesion G-protein-coupled receptor (GPCR), in MDA-MB-231 breast cancer cells. Furthermore, LPE signaling was suggested as like LPA1/CD97-Gi/o proteins-phospholipase C-IP3-Ca2+ increase in these cells. In the present study, we further investigated actions of LPE not only in the [Ca2+]i increasing effect but also in cell proliferation and migration in MDA-MB-231 breast cancer cells. We utilized chemically different LPEs and a specific inhibitor of LPA1, AM-095 in comparison with responses in SK-OV3 ovarian cancer cells. It was found that LPE-induced Ca2+ response in MDA-MB-231 cells was evoked in a different manner to that in SK-OV3 cells in terms of structural requirements. AM-095 inhibited LPE-induced Ca2+ response and cell proliferation in MDA-MB-231 cells, but not in SK-OV3 cells, supporting LPA1 involvement only in MDA-MB-231 cells. LPA had significant effects on cell proliferation and migration in MDA-MB-231 cells, whereas LPE had less or no significant effect. However, LPE modulations of MAPKs (ERK1/2, JNK and p38 MAPK) was not different to those by LPA in the cells. These data support the involvement of LPA1 in LPE-induced Ca2+ response and cell proliferation in breast MDA-MB-231 cells but unknown GPCRs (not LPA1) in LPE-induced responses in SK-OV3 cells. Furthermore, although LPE and LPA utilized LPA1, LPA utilized more signaling cascades than LPE, resulting in stronger responses by LPA in proliferation and migration than LPE in MDA-MB-231 cells.

Signaling Pathway of Lysophosphatidic Acid-Induced Contraction in Feline Esophageal Smooth Muscle Cells

Lysolipids such as LPA, S1P and SPC have diverse biological activities including cell proliferation, differentiation, and migration. We investigated signaling pathways of LPA-induced contraction in feline esophageal smooth muscle cells. We used freshly isolated smooth muscle cells and permeabilized cells from cat esophagus to measure the length of cells. Maximal contraction occurred at 10(-6) M and the response peaked at 30s. To identify LPA receptor subtypes in cells, western blot analysis was performed with antibodies to LPA receptor subtypes. LPA1 and LPA3 receptor were detected at 50 kDa and 44 kDa. LPA-induced contraction was almost completely blocked by LPA receptor (1/3) antagonist KI16425. Pertussis toxin (PTX) inhibited the contraction induced by LPA, suggesting that the contraction is mediated by a PTX-sensitive G protein. Phospholipase C (PLC) inhibitors U73122 and neomycin, and protein kinase C (PKC) inhibitor GF109203X also reduced the contraction. The PKC-mediated contraction may be isozyme-specific since only PKCepsilon antibody inhibited the contraction. MEK inhibitor PD98059 and JNK inhibitor SP600125 blocked the contraction. However, there is no synergistic effect of PKC and MAPK on the LPA-induced contraction. In addition, RhoA inhibitor C3 exoenzyme and ROCK inhibitor Y27632 significantly, but not completely, reduced the contraction. The present study demonstrated that LPA-induced contraction seems to be mediated by LPA receptors (1/3), coupled to PTX-sensitive G protein, resulting in activation of PLC, PKC-epsilon pathway, which subsequently mediates activation of ERK and JNK. The data also suggest that RhoA/ROCK are involved in the LPA-induced contraction.

Activation of Lysophosphatidic Acid Receptor Is Coupled to Enhancement of Ca(2+)-Activated Potassium Channel Currents

The calcium-activated K+ (BKCa) channel is one of the potassium-selective ion channels that are present in the nervous and vascular systems. Ca2+ is the main regulator of BKCa channel activation. The BKCa channel contains two high affinity Ca2+ binding sites, namely, regulators of K+ conductance, RCK1 and the Ca2+ bowl. Lysophosphatidic acid (LPA, 1-radyl-2-hydroxy-sn-glycero-3-phosphate) is one of the neurolipids. LPA affects diverse cellular functions on many cell types through G protein-coupled LPA receptor subtypes. The activation of LPA receptors induces transient elevation of intracellular Ca2+ levels through diverse G proteins such as Galphaq/11, Galphai, Galpha12/13, and Galphas and the related signal transduction pathway. In the present study, we examined LPA effects on BKCa channel activity expressed in Xenopus oocytes, which are known to endogenously express the LPA receptor. Treatment with LPA induced a large outward current in a reversible and concentration-dependent manner. However, repeated treatment with LPA induced a rapid desensitization, and the LPA receptor antagonist Ki16425 blocked LPA action. LPA-mediated BKCa channel activation was also attenuated by the PLC inhibitor U-73122, IP3 inhibitor 2-APB, Ca2+ chelator BAPTA, or PKC inhibitor calphostin. In addition, mutations in RCK1 and RCK2 also attenuated LPA-mediated BKCa channel activation. The present study indicates that LPA-mediated activation of the BKCa channel is achieved through the PLC, IP3, Ca2+, and PKC pathway and that LPA-mediated activation of the BKCa channel could be one of the biological effects of LPA in the nervous and vascular systems.

Expression of endothelial differemtiation gene receptors in human pancreatic cancer / 中华胰腺病杂志

ObjectiveTo evaluate the expression of endothelial differentiation gene/lysophosphatidic acid (LPA) receptors (Edg/LPA) and its clinical significance in human pancreatic cancer.MethodsFifty cases of pancreatic cancer and adjacent normal tissues were collected,and Real-time PCR,Western blot and immunohistochemistry was used to determine the expression of Edg-2/LPA1,Edg-4/LPA2 and Edg-7/LPA3 receptors mRNA and protein,and its relationship with clinicopathological parameters was analyzed.Results The expressions of Edg-2/LPA1,Edg-4/LPA2,Edg-7/LPA3 receptor mRNA were (0.142 ± 0.042 ) ％,(0.471 ±0.064)％,(0.231 ±0.043)％ in pancreatic cancer,and the corresponding values were (0.132 ±0.029)％,(0.027 ±0.015)％,(0.163 ±0.046)％ in adjacent normal tissues.The expressions of Edg-4/LPA2 receptor mRNA in pancreatic cancer were significantly lower than that in adjacent normal tissues ( P ＜0.05 ).The expressions of Edg-4/LPA2 receptor protein in pancreatic cancer were significantly lower than that in adjacent normal tissues ( P ＜ 0.05 ).The expressions of three types of Edg /LPA receptor mRNA in pancreatic cancer were parallel to serum CA19-9 levels.The expressions of Edg-4/LPA2 receptor mRNA were associated with tumor size,differentiation degree,and invasive ability and metastasis.While the expressions of Edg-2/LPA1,Edg-7/LPA3 receptor mRNA was associated with invasive ability and metastasis only.ConclusionsEdg-4/LPA2 receptor is highly expressed in pancreatic cancer,which suggesting the malignant biological behavior of pancreatic cancer.

Soporte nutricional en enfermedad pulmonar: una revisión sistemática / Parenteral nutrition in chronic obstructive pulmonary disease / Suporte nutricional em enfermidade pulmonar: uma revisão sistemática

Introducción: los pacientes con enfermedad pulmonar aguda (Síndrome de Dificultad Respiratoria Aguda -SDRA/ Lesión Pulmona Aguda-LPA) o crónica(Enfermedad Pulmonar Obstructiva Crónica- EPOC), presentan una importante alteración de su estado nutricional. La pérdida de peso tiene un efecto negativo en el curso clínico de estos pacientes. Las causas incluyen un disbalance energético, un incremento en las citoquinas, hipoxia y uso de glucocorticoides. El soporte nutricional está usualmente indicado como terapéutica o como apoyo en eltratamiento. Métodos: ésta es una revisión sistemática de literatura que consultó 1.026 números y seleccionó 87 artículos por su calidad y pertinencia.Resultados: se han propuesto diversas fórmulas de Nutrición Enteral (NE) yparenteral (NP) para contrarrestar los efectos adversos relacionados con elincremento en las demandas de ventilación mecánica de los pacientes alimentados con fórmulas estándar con altos contenidos de carbohidratos. Sin embargo, el uso de fórmulas especiales en pacientes con enfermedad pulmonar sigue siendo objeto de controversia.Conclusión: esta revisión sistemática tuvo como propósito mostrar los principales factores asociados con la malnutrición en las enfermedades pulmonares y examinar objetivamente el uso de las fórmulas de nutrición enteral y parenteral en enfermedad pulmonar aguda y crónica. Incluye los estudios que evalúan la eficacia de estas fórmulas y aporta recomendaciones básicas para su uso en enfermedades pulmonares específicas.

Introduction: the potential for altered nutritional status in critically ill patients with either acute (Acute Respiratory Distress Syndrome-ARDS/Acute Lung Injury-ALI) or chronic pulmonary disease (Chronic Obstructive Pulmonary Disease) is significant. Weight loss in patients with chronic obstructive pulmonary disease has a negative effect on the clinical course of the patient. Causes of weight loss in this population are known to include effects of an energy imbalance, increased cytokines, hypoxia, and glucocorticoid use. Nutritional support is often indicated as a treatment modality. Methods: we searched 1026 articles and was selected 87 articles. Results: several enteral and parenteral formulas (EN-PN) have been suggested to help counteract the possible adverse respiratory effects associated with a standard formula with higher carbohydrates content to reduce ventilator demand of the patients. However, the use of these specialized enteral formulas in individuals with pulmonary disease remains controversial. Conclusion: the purposes of this systematic review was to synthesize the factors associated with malnutrition in pulmonary diseases and to evaluate the rationale for use of modified parenteral and enteral formulas in both chronic and acute pulmonary disease. This paper includes the available studies evaluating the efficacy of these formulas, and provides overall recommendations for the use of specialized formulas in individuals with pulmonary disease.

Introdução: os pacientes com enfermidade pulmonar aguda (Síndrome de Dificuldade Respiratória Aguda -SDRA/ Lesão Pulmonar Aguda -LPA) ou crônica (Enfermidade Pulmonar Obstrutiva Crônica- EPOC), apresentam uma importante alteração de seu estado nutricional. A perda de peso tem um efeito negativo no curso clínico destes pacientes. As causas incluem um desequilíbrio energético, um incremento nas citoquimicas, hipoxia e uso de glucocorticoides. O suporte nutricional está usualmente indicado como terapêutico ou como apoio no tratamento. Métodos: este é uma revisão sistemática da literatura que consultou 1026 números e selecionou 87 artigos por sua qualidade e pertinência. Resultados: têm-se proposto diversas fórmulas de Nutrição Enteral (NE) e parenteral (NP) para contra restar os resultados adversos relacionados ao incremento nas demandas de ventilação mecânica dos pacientes alimentados com fórmulas uniformes com altos conteúdos de carboidratos. Mas o uso de fórmulas especiais em pacientes com doenças pulmonar segue sendo objeto de controvérsia. Conclusão: esta revisão sistemática teve como propósito mostrar os principais fatores associados à má nutrição nas enfermidades pulmonares e examinar objetivamente o uso das fórmulas de nutrição enteral e parenteral em enfermidades pulmonares agudas e crônicas. Inclui estudos que avaliam a eficácia destas fórmulas e traz recomendações básicas para seu uso em enfermidades pulmonares específicas.

Correlation among Thromboxane B2, Oxidized Low Density Lipoprotein, Lipoprotein(a), and Homocysteine in Patients with Cerebral Infarction / 中国康复理论与实践

@#ObjectiveTo study the relevant pathogenic factors, Thromboxane B2 (TXB2), oxidized low density lipoprotein (OxLDL), lipoprotein(a) (Lp(a)), and homocysteine (Hcy), in patients with cerebral infarction and the correlation among them. Methods205 patients and 40 health persons (the control) were measured with the plasma TXB2, 6-keto-prostaglandin F1α (PGF1α) and TXB2/6-keto-PGF1α (T/6-K), OxLDL, Lp(a), Hcy within 24 h. Results and ConclusionThe levels of plasma TXB2, T/6-K，OxLDL, Lp(a), and Hcy significantly increased compared with the controls (P<0.01). OxLDL was correlated with Lp(a); TXB2 was correlated with T/6-K and Hcy; T/6-K was correlated with OxLDL, Lp（a）.