The outcome and predictive model of allogeneic hematopoietic stem cell transplantation among elderly patients with severe aplastic anemia from the Chinese Blood and Marrow Transplant Registry Group.

Not available.

Leucine zipper protein 1 attenuates pressure overload-induced cardiac hypertrophy through inhibiting Stat3 signaling.

INTRODUCTION: Cardiac hypertrophy is an important contributor of heart failure, and the mechanisms remain unclear. Leucine zipper protein 1 (LUZP1) is essential for the development and function of cardiovascular system; however, its role in cardiac hypertrophy is elusive. OBJECTIVES: This study aims to investigate the molecular basis of LUZP1 in cardiac hypertrophy and to provide a rational therapeutic approach. METHODS: Cardiac-specific Luzp1 knockout (cKO) and transgenic mice were established, and transverse aortic constriction (TAC) was used to induce pressure overload-induced cardiac hypertrophy. The possible molecular basis of LUZP1 in regulating cardiac hypertrophy was determined by transcriptome analysis. Neonatal rat cardiomyocytes were cultured to elucidate the role and mechanism of LUZP1 in vitro. RESULTS: LUZP1 expression was progressively increased in hypertrophic hearts after TAC surgery. Gain- and loss-of-function methods revealed that cardiac-specific LUZP1 deficiency aggravated, while cardiac-specific LUZP1 overexpression attenuated pressure overload-elicited hypertrophic growth and cardiac dysfunction in vivo and in vitro. Mechanistically, the transcriptome data identified Stat3 pathway as a key downstream target of LUZP1 in regulating pathological cardiac hypertrophy. Cardiac-specific Stat3 deletion abolished the pro-hypertrophic role in LUZP1 cKO mice after TAC surgery. Further findings suggested that LUZP1 elevated the expression of Src homology region 2 domain-containing phosphatase 1 (SHP1) to inactivate Stat3 pathway, and SHP1 silence blocked the anti-hypertrophic effects of LUZP1 in vivo and in vitro. CONCLUSION: We demonstrate that LUZP1 attenuates pressure overload-induced cardiac hypertrophy through inhibiting Stat3 signaling, and targeting LUZP1 may develop novel approaches to treat pathological cardiac hypertrophy.

LncRNA MALAT1 Promotes PPARα/CD36-Mediated Hepatic Lipogenesis in Nonalcoholic Fatty Liver Disease by Modulating miR-206/ARNT Axis.

Long non-coding RNAs (lncRNAs) are known to play crucial roles in nonalcoholic fatty liver disease (NAFLD). This research sought to explore mechanisms by which lncRNA MALAT1 regulates the progression of NAFLD. Thus, in order to detect the function of MALAT1 in NAFLD, in vitro and in vivo model of NAFLD were established. Then, fatty acid uptake and triglyceride level were investigated by BODIPY labeled-fatty acid uptake assay and Oil red O staining, respectively. The expressions of MALAT1, miR-206, ARNT, PPARα and CD36 were detected by western blotting and qPCR. Dual luciferase, RIP and ChIP assay were used to validate the relation among MALAT1, miR-206, ARNT and PPARα. The data revealed expression of MALAT1 was up-regulated in vitro and in vivo in NAFLD, and knockdown of MALAT1 suppressed FFA-induced lipid accumulation in hepatocytes. Meanwhile, MALAT1 upregulated the expression of ARNT through binding with miR-206. Moreover, miR-206 inhibitor reversed MALAT1 knockdown effects in decreased lipid accumulation in FFA-treated hepatocytes. Furthermore, ARNT could inhibit the expression of PPARα via binding with PPARα promoter. Knockdown of MALAT1 significantly upregulated the level of PPARα and downregulated the expression of CD36, while PPARα knockdown reversed these phenomena. MALAT1 regulated PPARα/CD36 -mediated hepatic lipid accumulation in NAFLD through regulation of miR-206/ARNT axis. Thus, MALAT1/miR-206/ARNT might serve as a therapeutic target against NAFLD.

Iodoarene-Catalyzed Oxyamination of Unactivated Alkenes to Synthesize 5-Imino-2-Tetrahydrofuranyl Methanamine Derivatives.

Reported here is the room-temperature metal-free iodoarene-catalyzed oxyamination of unactivated alkenes. In this process, the alkenes are difunctionalized by the oxygen atom of the amide group and the nitrogen in an exogenous HNTs2 molecule. This mild and open-air reaction provided an efficient synthesis to N-bistosyl-substituted 5-imino-2-tetrahydrofuranyl methanamine derivatives, which are important motifs in drug development and biological studies. Mechanistic study based on experiments and density functional theory calculations showed that this transformation proceeds via activation of the substrate alkene by an in situ generated cationic iodonium(III) intermediate, which is subsequently attacked by an oxygen atom (instead of nitrogen) of amides to form a five-membered ring intermediate. Finally, this intermediate undergoes an SN2 reaction by NTs2 as the nucleophile to give the oxygen and nitrogen difunctionalized 5-imino-2-tetrahydrofuranyl methanamine product. An asymmetric variant of the present alkene oxyamination using chiral iodoarenes as catalysts also gave promising results for some of the substrates.

Evaluation of the exposure risk of SARS-CoV-2 in different hospital environment.

The ongoing coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has imposed a significant impact on social and economic activities. As a high infectious pathogen, the existence of SARS-CoV-2 in public space is very important for its transmission. During the COVID-19 pandemic, hospitals are the main places to deal with the diseases. In this work, we evaluated the exposure risk of SARS-CoV-2 in hospital environment in order to protect healthcare workers (HCWs). Briefly, air and surface samples from 6 different sites of 3 hospitals with different protection levels were collected and tested for the SARS-CoV-2 nucleic acid by reverse transcription real-time fluorescence PCR method during the COVID-19 epidemic. We found that the positive rate of SARS-CoV-2 nucleic acid was 7.7 % in a COVID-19 respiratory investigation wards and 82.6 % in a ICUs with confirmed COVID-19 patients. These results indicated that in some wards of the hospital, such as ICUs occupied by COVID-19 patients, the nucleic acid of SARS-CoV-2 existed in the air and surface, which indicates the potential occupational exposure risk of HCWs. This study has clarified retention of SARS-CoV-2 in different sites of hospital, suggesting that it is necessary to monitor and disinfect the SARS-CoV-2 in hospital environment during COVID-19 pandemic, and will help to prevent the iatrogenic infection and nosocomial transmission of SARS-CoV-2 and to better protect the HCWs.

Expression patterns of intermediate filament proteins desmin and lamin A in the developing conduction system of early human embryonic hearts.

Since embryonic heart development is a complex process and acquisition of human embryonic specimens is challenging, the mechanism by which the embryonic conduction system develops remains unclear. Herein, we attempt to gain insights into this developmental process through immunohistochemical staining and 3D reconstructions. Expression analysis of T-box transcription factor 3, cytoskeleton desmin, and nucleoskeleton lamin A protein in human embryos in Carnegie stages 11-20 showed that desmin is preferentially expressed in the myocardium of the central conduction system compared with the peripheral conduction system, and is co-expressed with T-box transcription factor 3 in the central conduction system. Further, lamin A was first expressed in the embryonic ventricular trabeculations, where the terminal ramifications of the peripheral conduction system develop, and extended progressively to all parts of the central conduction system. The uncoupled spatiotemporal distribution pattern of lamin A and desmin indicated that the association of cytoskeleton desmin and nucleoskeleton lamin A may be a late event in human embryonic heart development. Compared with model animals, our data provide a direct morphological basis for understanding the arrhythmogenesis caused by mutations in human DES and LMNA genes.

Isl-1 positive pharyngeal mesenchyme subpopulation and its role in the separation and remodeling of the aortic sac in embryonic mouse heart.

BACKGROUND: Second heart field cells and neural crest cells have been reported to participate in the morphogenesis of the pharyngeal arch arteries (PAAs); however, how the PAAs grow out and are separated from the aortic sac into left and right sections is unknown. RESULTS: An Isl-1 positive pharyngeal mesenchyme protrusion in the aortic sac ventrally extends and fuses with the aortic sac wall to form a midsagittal septum that divides the aortic sac. The aortic sac division separates the left and right PAAs to form independent arteries. The midsagittal septum dividing the aortic sac has a different expression pattern from the aortic-pulmonary (AP) septum in which Isl-1 positive cells are absent. At 11 days post-conception (dpc) in a mouse embryo, the Isl-1 positive mesenchyme protrusion appears as a heart-shaped structure, in which subpopulations with Isl-1+ Tbx3+ and Isl-1+ Nkx2.5+ cells are included. CONCLUSIONS: The aortic sac is a dynamic structure that is continuously divided during the migration from the pharyngeal mesenchyme to the pericardial cavity. The separation of the aortic sac is not complete until the AP septum divides the aortic sac into the ascending aorta and pulmonary trunk. Moreover, the midsagittal septum and the AP septum are distinct structures.

Canonical Transient Receptor Potential Channels and Their Link with Cardio/Cerebro-Vascular Diseases.

The canonical transient receptor potential channels (TRPCs) constitute a series of nonselective cation channels with variable degrees of Ca2+ selectivity. TRPCs consist of seven mammalian members, TRPC1, TRPC2, TRPC3, TRPC4, TRPC5, TRPC6, and TRPC7, which are further divided into four subtypes, TRPC1, TRPC2, TRPC4/5, and TRPC3/6/7. These channels take charge of various essential cell functions such as contraction, relaxation, proliferation, and dysfunction. This review, organized into seven main sections, will provide an overview of current knowledge about the underlying pathogenesis of TRPCs in cardio/cerebrovascular diseases, including hypertension, pulmonary arterial hypertension, cardiac hypertrophy, atherosclerosis, arrhythmia, and cerebrovascular ischemia reperfusion injury. Collectively, TRPCs could become a group of drug targets with important physiological functions for the therapy of human cardio/cerebro-vascular diseases.

PBEF promotes the apoptosis of pulmonary microvascular endothelial cells and regulates the expression of inflammatory factors and AQP1 through the MAPK pathways.

Pre-B cell colony-enhancing factor (PBEF) has been shown to have a variety of biological functions. Studies have proven that PBEF plays a functional role in acute lung injury (ALI). Therefore, in this study, we aimed to confirm the importance of PBEF in ALI. The effects of PBEF overexpression on the apoptosis of human pulmonary microvascular endothelial cells (HPMECs) were analyzed by flow cytometry, and the results indicated that PBEF promoted the apoptosis of HPMECs, which aggravated the development of ALI. Comparative experiments involving increasing and decreasing PBEF expression demonstrated that PBEF promoted the expression of inflammatory factors, such as interleukin (IL)­1ß, IL­6 and IL­8 in the HPMECs , thus intensifying the inflammatory response. PBEF also inhibited the expression of aquaporin 1 (AQP1), which caused a dysfunction and imbalance in water transport. Moreover, we also found that tumor necrosis factor (TNF)­α promoted the expression of PBEF in the HPMECs. After blocking the mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K) pathways, we found that PBEF regulated the expression of inflammatory factors and AQP1, mainly through the MAPK pathways. Taken together, these results demonstrate that the increase in intracellular PBEF expression promoted the apoptosis of HPMECs and the expression of inflammatory factors and thus enhanced the inflammatory response and inhibited the expression of AQP1, which resulted in abnormal water transport, diminishing the regulatory effects of AQP1 on water transport.

JAZF1 regulates visfatin expression in adipocytes via PPARα and PPARß/δ signaling.

OBJECTIVE: Current whole genome-wide association study has identified the association of JAZF1 with type 2 diabetes; its close relation with glucose and lipid metabolism has also been revealed. However, to date, JAZF1 remains a relatively new gene with unknown function. MATERIALS/METHODS: We constructed JAZF1 overexpression vector and synthesized JAZF1 siRNA, then transfected them into 3T3-L1 adipocytes, investigated the relationship between the regulations of JAZF1, visfatin, and other adipokines, researched the specific function of JAZF1 in glucose and lipid metabolism. RESULTS: This study found that the expression of JAZF1 was gradually but significantly upregulated during the induced differentiation of 3T3-L1 preadipocytes, and that the trend of its expression was consistent with that of visfatin. Further studies indicated that JAZF1 promoted the expressions of visfatin, PPARα, and PPARß/δ in adipocytes but simultaneously inhibited the expressions of TAK1 and PPARγ. Luciferase reporter assay revealed that JAZF1 activated the transcription of visfatin, but ChIP assay results indicated that JAZF1 did not directly bind to visfatin PPRE. Our results also showed that the JAZF1 overexpression-increased visfatin expression was abolished by the addition of PPARα antagonist GW 6471 and PPARß/δ antagonist GSK 3787 respectively. And these results were further confirmed by the experiment with PPARα and PPARß/δ siRNAs. Meanwhile, we also found that JAZF1 inhibited the lipid accumulation during the differentiation of 3T3-L1 into mature adipocyte. CONCLUSIONS: Our results indicate that JAZF1 might firstly upregulated the expression of PPARα and PPARß/δ, which in turn activated the transcription of visfatin. JAZF1 plays an important role in lipid metabolism and may thus provide a potential tool for the treatment of obesity and lipid metabolism disorders among other diseases.

JAZF1 can regulate the expression of lipid metabolic genes and inhibit lipid accumulation in adipocytes.

JAZF1 is a newly identified gene with unknown functions. A recent genome-wide association study showed that JAZF1 is associated with type 2 diabetes and is highly expressed in liver and adipose tissue. Studies have demonstrated that JAZF1 is the co-repressor for nuclear orphan receptor TAK1, whereas most nuclear orphan receptor family members are involved in the regulation of lipid metabolism. Therefore, JAZF1 could be closely related to glycolipid metabolism. In this study, JAZF1 was significantly upregulated during the induced differentiation process of 3T3-L1 preadipocytes. The overexpression of JAZF1 inhibited lipid accumulation in differentiated mature 3T3-L1 adipocytes and significantly inhibited the expression of SREBPl, ACC, and FAS, which were important in lipid synthesis, while upregulating the expression of key enzyme hormone-sensitive lipase in lipoclasis. Moreover, SREBPl exhibited an inhibitory function on the expression of JAZF1. SREBP1 reversed the inhibitory action on lipid accumulation of JAZF1. SREBP1 and JAZF1 were observed to regulate each other in adipocytes. Therefore, JAZF1 could regulate the expression of particular genes related to lipid metabolism and inhibit lipid accumulation in adipocytes. This result suggests that JAZF1 may be a potential target for the treatment of diseases, such as obesity and lipid metabolism disorders.

[Effects of hydrogen sulfide on ouabain-induced delayed after-depolarization and triggered activity in guinea pig papillary muscles].

OBJECTIVE: To explore the effects of hydrogen sulfide (H(2)S) on delayed after-depolarization (DAD) and triggered activity induced by ouabain in male guinea pig papillary muscles and to elucidate the underlying mechanisms. METHODS: An intracellular microelectrode was used to record the patterns of DAD and triggered activity by K-H solution containing ouabain and a high concentration of calcium ion. The latent period, amplitude, duration of DAD and incidence of triggered activity were observed under a pre-treatment with different concentrations of NaHS (donor of H(2)S). The effects of glibenclamide, Bay K8644 and NG-nitro-L-arginine methyl ester (L-NAME) pretreatment on the actions of H(2)S were also studied. RESULTS: NaHS (100, 200 µmol/L) prolonged the latent period of DAD from (12.0 ± 1.0) min to (19.9 ± 1.6) min (P < 0.05), (23.7 ± 1.3) min (P < 0.01), decreased the altitude of DAD from (11.47 ± 0.74) mV to (6.47 ± 0.33) mV, (5.65 ± 0.26) mV (both P < 0.01), shortened the duration of DAD from (205 ± 11) ms to (173 ± 10) ms and (134 ± 7) ms (both P < 0.05). The occurrence of triggered activity was inhibited from 5 samples to 4, 2 and 1 sample in 6 samples. A pretreatment of adenosine triphosphate (ATP)-sensitive potassium channel (K(ATP)) blocker glibenclamide partially blocked the preventive effects of H(2)S on ouabain-induced DAD and triggered activity. The effects of H(2)S were completely blocked by L-type calcium channel agonist Bay K8644 (0.25 µmol/L). However a pretreatment of L-NAME (1 mmol/L), a nitric oxide (NO) synthase inhibitor, showed no effects on H(2)S. CONCLUSION: H(2)S inhibits the ouabain-induced DAD and triggered activity in guinea pig papillary muscles. The opening of K(ATP) channel with a reduced influx of calcium ion may be involved in the protective effects of H(2)S.

Specification of region-specific neurons including forebrain glutamatergic neurons from human induced pluripotent stem cells.

BACKGROUND: Directed differentiation of human induced pluripotent stem cells (hiPSC) into functional, region-specific neural cells is a key step to realizing their therapeutic promise to treat various neural disorders, which awaits detailed elucidation. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed neural differentiation from various hiPSC lines generated by others and ourselves. Although heterogeneity in efficiency of neuroepithelial (NE) cell differentiation was observed among different hiPSC lines, the NE differentiation process resembles that from human embryonic stem cells (hESC) in morphology, timing, transcriptional profile, and requirement for FGF signaling. NE cells differentiated from hiPSC, like those from hESC, can also form rostral phenotypes by default, and form the midbrain or spinal progenitors upon caudalization by morphogens. The rostrocaudal neural progenitors can further mature to develop forebrain glutamatergic projection neurons, midbrain dopaminergic neurons, and spinal motor neurons, respectively. Typical ion channels and action potentials were recorded in the hiPSC-derived neurons. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that hiPSC, regardless of how they were derived, can differentiate into a spectrum of rostrocaudal neurons with functionality, which supports the considerable value of hiPSC for study and treatment of patient-specific neural disorders.

[Role of JNK signal transduction pathway in nonalcoholic fatty liver disease].

OBJECTIVE: To investigate the role of c-Jun N-terminal kinase (JNK) signal transduction pathway in the rats of nonalcoholic fatty liver disease (NAFLD). METHODS: Sixty four Sprague-Dawley rats were randomly divided into four groups: 8-week control group (NG8w), 12-week control group (NG12 w), 8-week high-fat diet (HG8w), and 12-week high-fat diet group (HG12w), with 16 rats in each group. Glucose infusion rate (GIR) was tested by euglycemic hyperinsulinemic clamp; aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), total cholesterol (TC), free fatty acid (FFAs), fast insulin (FIns), tumor necrosis factor alpha (TNF alpha), superoxide dismutase (SOD) and malondialdehyde (MDA) were tested by biochemistry automatic analyzer or RIA; The expression of JNK1, insulin receptor substrate-1 (IRS-1), phospho-IRS-1 Ser307 (p-IRS-1 Ser307), Protein kinase B (PKB) and phospho-PKB Ser473 (p- PKB Ser473) were detected by Western blot. RESULTS: Compared to control group, body weight, liver index, serum levels of ALT, AST, TG, TC, FIns, FFAs, TNF alpha, and TC, TG FFAs, MDA in liver homogenates were increased, while the level of SOD, and GIR were decreased. The expression of JNK1 protein and p-IRS-1 Ser307 in liver tissue was up-regulated, while expression of p-PKB Ser473 was decreased (P < 0.05). A positive correlation was found between the expression intensity of JNK1 and IR (Pearson correlation: 0.718, P < 0.01). CONCLUSION: The high-fat could induce the expression of JNK1, which in turn modulates the phosphorylation of proteins in the insulin signaling pathway, and induces insulin resistant.

[Clinical analysis of coronary artery disease in elderly patients with sleep disordered breathing].

OBJECTIVE: To understand the prevalence of sleep disordered breathing (SDB) in elderly patients with coronary artery disease (CAD) and explore the relations between SDB and CAD. METHODS: Sixty-two elderly patients with and 18 without CAD identified by coronary angiography underwent examinations by polysomnography (PSG). Left ventricular ejection fraction (LVEF) was measured by 99Tc equilibrium radionuclide angiography. RESULTS: In the 62 elderly patients with CAD, 53.2% had SDB, a rate significantly higher that (22.2%) in the 18 non-CAD patients. The CAD patients with SDB had higher respiratory disturbance index (RDI) and body mass index (BMI) and lower arterial saturation of oxygen (SaO2) during sleep, with longer duration of low SPO2 (less that 90%). The incidence of hypertension was higher in CAD patients with SDB than in those without SDB. No significant correlation was found between the severity of coronary artery disease and RDI (r=-0.16, P>0.05). CONCLUSION: The elderly patients with CAD have higher incidence of SDB, and appropriate interventions should be administered in those with severe SDB.

[Molecular mechanisms of insect pests-induced plant defense].

This paper reviewed the newest research advances in insect pests-induced plant defense, including insect pests-induced system wounding signals of plants, elicitors of insects, indirect defense, direct defense, and negative defense. In the interactions between plants and insect pests, plants can use the induced defensive substances to counteract insect pests, while the latter can use their specific elicitors to beat plant defense. This paper also compared the four metabolic pathways involved in indirect defense, i. e., lipoxygenase pathway, isoprenoid pathway, shikimate pathway, and extrfloral nectar, discussed the release mechanisms of induced volatile organic compounds in plants, and illustrated the conception of direct defense, defensive substances, and their action mechanisms. Finally, the research advances in the mechanisms of inset pests-induced negative defense of plants were reviewed, with the focus on the molecular mechanisms of insect pests-induced defense of forests.

[Relationship between chronic congestive heart failure and sleep-disordered breathing in elderly patients].

OBJECTIVE: To determine the prevalence of sleep disordered breathing (SDB) in elderly patients with chronic congestive heart failure (CHF) and explore the relations between SDB and left ventricular function. METHODS: By means of polysomnography, 56 elderly patients with CHF were divided into non-SDB, mild SDB, moderate SDB, and severe SDB groups, and the left ventricular ejection fraction (LVEF) was measure by (99)Tc equilibrium radionuclide angiography. RESULTS: In the 56 elderly patients with CHF, 38 (67.9%) had SDB, including 12 (21.4%) mild SDB, 14 (25.0%) moderate SDB, and 12 (21.4%) severe SDB patients. Thirty (53.6%) of the 56 patients with CHF had obstructive sleep apnea (OSA), 4 (7.1%) had central sleep apnea and 22 (39.2%) had mixed sleep apnea. The moderate and severe SDB groups had lower minimum arterial oxyhemoglobin saturation during sleep than the non-SDB groups, and the apnea-hyponea index was closely related to LVEF (r=-0.74, P<0.01). CONCLUSION: The prevalence of SDB, predominantly OSA, is high in elderly patients with CHF. Moderate and severe SDB might affect the left ventricular function in these patients, who require polysomnography monitoring.

[Effect of atorvastatin on the nuclear factor-kappaB and soluble inter-cellular adhesion molecules-1 in patients with acute coronary syndrome].

OBJECTIVE: To determine the effect of atorvastatin on the activity of peripheral blood lymocyte nuclear factor-kappaB (NF-kappaB) and plasma soluble inter-cellular adhesion molecules-1 (sICAM-1) in acute coronary syndromes. METHODS: Sixty-eight patients with acute coronary syndrome were randomly divided into atorvastatin therapeutic group (n = 37) and conventional therapeutic group (n = 31). Enzyme-linked immunosorbent assay was used to measure the plasma sICAM-1, and immunohistochemical method was used to measure the activity of NF-kappaB in the peripheral blood lymphocyte before and 12 weeks after the therapy in the two groups. RESULTS: Before the therapy, the level of NF-kappaB activity in the peripheral blood lymphocytes [(45.2 +/- 8.4)% vs (40.8 +/- 9.2)%, P > 0.05] and the plasma sICAM-1 [(357.2 +/- 84.5) ng/ml vs (365.5 +/- 91.3) ng/ml, P > 0.05] in the two groups had no significant difference. After 12 weeks of the therapy, in the conventional group the level of NF-kappaB activity in the peripheral blood lymphocytes [(40.8 +/- 9.2)% vs (38.7 +/- 8.9)%, P > 0.05] and the plasma sICAM-1 [(357.2 +/- 84.5) ng/ml vs (365.5 +/- 91.3) ng/ml, P > 0.05] still had no significant difference. But in the atorvastatin group the level of NF-kappaB activity in the peripheral blood lymphocyte [(45.2 +/- 8.4)% vs (25.6 +/- 7.9)%, P < 0.05 and the plasma soluble inter-cellular adhesion molecule-1 [(357.2 +/- 84.5) ng/ml vs (175.8 +/- 75.6) ng/ml, P < 0.05] did show a significant difference. CONCLUSION: The cholesterol-lowering therapy with atorvastatin can reduce the inflammation and stabilize the plaque in the acute coronary syndrome, which may be related to the inhibition of NF-KB and sICAM-1 activities.

[Related inflammation markers among different types of coronary heart disease].

OBJECTIVE: To study the relationship between levels of activity of NF-kappaB p65, plasma soluble inter-cellular adhesion molecule-1, C-reactive protein on plaque stability, and different types of coronary heart disease. METHODS: We measured the levels of plasma soluble inter-cellular adhesion molecule-1 and C-reactive protein by enzyme-linked immunosorbant assay and the activity of NF-kappaB p65 in peripheral blood lymocytes immunohistochemically. RESULTS: Compared with the stable angina and the control group, the baseline activity of NF-kappaB p65, sICAM-1 and C-reactive protein was significantly elevated in the acute myocardial infarction and the unstable angina (P <0.01). After 3 month follow-up, the levels of activity of NF-kappaB p65 and sICAM-1 were unchanged (P > 0.05). In all groups, C-reactive proteins were lowered at the review (P <0.01). CONCLUSION: The levels of activity of NF-kappaB p65, sICAM-1 and C-reactive protein are related to the plaque stability among different types of coronary heart disease. NF-kappaB p65, and sICAM-1 are not affected by the acute event. These plasma markers may be important risk factors for the development of the acute coronary syndrome.

High glucose and insulin in combination cause insulin receptor substrate-1 and -2 depletion and protein kinase B desensitisation in primary cultured rat adipocytes: possible implications for insulin resistance in type 2 diabetes.

OBJECTIVE: The purpose of this study was to investigate the cellular effects of long-term exposure to high insulin and glucose levels on glucose transport and insulin signalling proteins. DESIGN AND METHODS: Rat adipocytes were cultured for 24 h in different glucose concentrations with 10(4) microU/ml of insulin or without insulin. After washing, (125)I-insulin binding, basal and acutely insulin-stimulated d-[(14)C]glucose uptake, and insulin signalling proteins and glucose transporter 4 (GLUT4) were assessed. RESULTS: High glucose (15 and 25 mmol/l) for 24 h induced a decrease in basal and insulin-stimulated glucose uptake compared with control cells incubated in low glucose (5 or 10 mmol/l). Twenty-four hours of insulin treatment decreased insulin binding capacity by approximately 40%, and shifted the dose-response curve for insulin's acute effect on glucose uptake 2- to 3-fold to the right. Twenty-four hours of insulin treatment reduced basal and insulin-stimulated glucose uptake only in the presence of high glucose (by approximately 30-50%). At high glucose, insulin receptor substrate-1 (IRS-1) expression was downregulated by approximately 20-50%, whereas IRS-2 was strongly upregulated by glucose levels of 10 mmol/l or more (by 100-400%). Insulin treatment amplified the suppression of IRS-1 when combined with high glucose and also IRS-2 expression was almost abolished. Twenty-four hours of treatment with high glucose or insulin, alone or in combination, shifted the dose-response curve for insulin's effect to acutely phosphorylate protein kinase B (PKB) to the right. Fifteen mmol/l glucose increased GLUT4 in cellular membranes (by approximately 140%) compared with 5 mmol/l but this was prevented by a high insulin concentration. CONCLUSIONS: Long-term exposure to high glucose per se decreases IRS-1 but increases IRS-2 content in rat adipocytes and it impairs glucose transport capacity. Treatment with high insulin downregulates insulin binding capacity and, when combined with high glucose, it produces a marked depletion of IRS-1 and -2 content together with an impaired sensitivity to insulin stimulation of PKB activity. These mechanisms may potentially contribute to insulin resistance in type 2 diabetes.