Acevaltrate promotes apoptosis and inhibits proliferation by suppressing HIF-1α accumulation in cancer cells.

Acevaltrate is a natural product isolated from the roots of Valeriana glechomifolia F.G.Mey. (Valerianaceae) and has been shown to exhibit anti-cancer activity. However, the mechanism by which acevaltrate inhibits tumor growth is not fully understood. We here demonstrated the effect of acevaltrate on hypoxia-inducible factor-1α (HIF-1α) expression. Acevaltrate showed a potent inhibitory activity against HIF-1α induced by hypoxia in various cancer cells. This compound markedly decreased the hypoxia-induced accumulation of HIF-1α protein dose-dependently. Further analysis revealed that acevaltrate inhibited HIF-1α protein synthesis and promoted degradation of HIF-1α protein, without affecting the expression level of HIF-1α mRNA. Moreover, the phosphorylation levels of mammalian target of rapamycin (mTOR), ribosomal protein S6 kinase (p70S6K), and eIF4E binding protein-1 (4E-BP1) were significantly suppressed by acevaltrate. In addition, acevaltrate promoted apoptosis and inhibited proliferation, which was potentially mediated by suppression of HIF-1α. We also found that acevaltrate administration inhibited tumor growth in mouse xenograft model. Taken together, these results suggested that acevaltrate was a potent inhibitor of HIF-1α and provided a new insight into the mechanisms of acevaltrate against cancers.

The protein tyrosine kinase inhibitor genistein suppresses hypoxia-induced atrial natriuretic peptide secretion mediated by the PI3K/Akt-HIF-1α pathway in isolated beating rat atria.

Genistein, an isoflavonoid that can inhibit protein tyrosine kinase (PTK) phosphorylation, has been shown to play pivotal roles in the signal transduction pathways of hypoxic disorders. In this study, we established a rat model of isolated beating atrium and investigated the regulator role of genistein and its downstream signaling pathways in acute hypoxia-induced atrial natriuretic peptide (ANP) secretion. Radioimmunoassay was used to detect the ANP content in the atrial perfusates. Western blot analysis was used to determine the protein level of hypoxia-inducible factor 1α (HIF-1α), and GATA4 in the atrial tissue. The results showed that acute hypoxia substantially promoted ANP secretion, whereas this effect was partly attenuated by the PTKs inhibitor genistein (3 µM). By Western blotting analysis, we found that hypoxia-induced increase in phosphorylation of Akt and transcriptional factors, including HIF-1α, were also reversed by genistein. The perfused HIF-1α inhibitors rotenone (0.5 µM) or CAY10585 (10 µM) plus genistein significantly abolished the enhanced ANP section induced by hypoxia. Additionally, the perfused PI3K/Akt agonist insulin-like growth factor 1 (30 µM) also abolished ANP secretion induced by genistein and inhibited expression of HIF-1α. In summary, our data suggested that acute hypoxia markedly increased ANP secretion by PTKs through the phosphoinositide-3 kinase (PI3K)/HIF-1α dependent pathway.

Application of Component Apheresis in Pre-deposited Autotransfusion.

OBJECTIVE: This study aims to evaluate the effects of preoperative autologous blood donation (PABD) using apheresis in patients who underwent elective surgical procedures, and investigate its clinical usefulness. METHODS: Data from 109 patients who underwent general and orthopedics elective surgery were analyzed in this study. Patients were divided into three groups: control group, patients who did not donate autologous blood; whole blood (WB) PABD group, patients who underwent preoperative autologous WB donation; autologous apheresis group, patients who donated autologous blood using erythrocytapheresis. Hb, Hct, and PLT levels in all patients were measured and compared before the operation and on postoperative days one and three. Furthermore, postoperative recovery indexes in the three groups were compared including allogeneic blood transfusions and postoperative hospitalization days. RESULTS: Hb, Hct, and PLT levels in the three groups after the operation were lower than levels before the operation. However, Hb levels were higher than 110 g/L and the Hct levels were not less than 33%. Differences in Hb and Hct drop values on postoperative days one and three among the three groups were statistically significant (P>0.05). Furthermore, PLT level in the control group was lower than in the WB PABD group and autologous apheresis group (P<0.05). PABD using erythrocytapheresis reduced blood transfusion (P<0.05). CONCLUSION: Erythrocytapheresis PABD led to an equal or even better postoperative recovery effect than WB PABD, and erythrocytapheresis PABD is feasible for blood transfusion therapy in patients undergoing elective surgical procedures.

Down-regulated miR-187 promotes oxidative stress-induced retinal cell apoptosis through P2X7 receptor.

Several microRNAs (miRNAs) expressed in the retina were confirmed to involve in retinal cell apoptosis, which was closely linked with the development of retinal diseases. Our previous studies have confirmed a vital role of miR-187 in retinal cells apoptosis. The aim of this study was to further elucidate the precise role of miR-187 and its probable mechanisms in RGC-5 cells apoptosis. The cellular oxidative stress status was assessed by reactive oxygen species (ROS) production and malondialdehyde (MDA) level. Our results showed that the elevated pressure, glutamate and H2O2-induced oxidative stress in RGC-5 cells was accompanied by a decrease in miR-187 expression and an increase in P2X7R expression. However, overexpression of miR-187 reversed this activation of oxidative stress in RGC-5 cells. Moreover, we also revealed that miR-187 inhibited the oxidative stress-induced apoptosis of RGC-5 cells through negative regulating P2X7R, probably through interacting with the 3'UTR of P2X7R. Finally, we confirmed that the forced miR-187 expression alleviated oxidative stress injury in retina tissues of rat models with chronic ocular hypertension. Our data demonstrated that miR-187/P2X7R signaling was involved in retinal cell apoptosis, at least in part, through activating oxidative stress.

Antiapoptotic role of the cellular repressor of E1A-stimulated genes (CREG) in retinal photoreceptor cells in a rat model of light-induced retinal injury.

OBJECTIVE: Light injury-induced apoptosis of retinal photoreceptor cells can lead to vision loss. The mechanism underlying such injury remains unclear, and there are no effective therapies at present. The aim of this study was to examine the potential antiapoptotic role of the cellular repressor of E1A-stimulated genes (CREG) in retinal cells in a rat model of light-induced retinal damage. METHODS: CREG proteins were injected into the vitreous space of rats in which light retinal injury was induced. An equal volume of PBS was injected into the vitreous space of a control group. Retinas were collected for H&E staining and Western blotting analysis 1, 3, and 7 days later. Inhibitors or agonist for P38, JNK, and AKT were injected into the vitreous space to verify CREG function. RESULTS: In rats with light-induced retinal injury, the CREG treatment inhibited the expression of apoptosis-related proteins caspase-3, caspase-8, and caspase-9 and signaling proteins phosphorylated ERK (P-ERK), phosphorylated JNK (P-JNK), phosphorylated P38 (P-P38), and phosphorylated AKT (P-AKT). An inhibitor of PI3K-AKT and an agonists of P38 and JNK abrogated the inhibitory effect of CREG on caspase-3 expression. CONCLUSION: CREG protected retinal cells against apoptosis by inhibiting P38/MAPK and JNK/MAPK signaling pathways and activating the PI3K-AKT signaling pathway.

Protective effects of a composition of Chinese herbs-Gurigumu-13 on retinal ganglion cell apoptosis in DBA/2J glaucoma mouse model.

AIM: To explore the concrete mechanism of a Mongolian compound medicine-Gurigumu-13 (GRGM) for glaucoma treatment. METHODS: DBA/2J mice, as glaucoma models, were intragastric administrated with GRGM to study the effect of GRGM on retinal ganglion cells (RGCs). The loss of RGCs was evaluated with the number of RGCs and axons. The expression of the target protein of RGCs or mouse retinas was determined by Western blot. The relative content of malondialdehyde (MDA) was examined by ELISA assay. RESULTS: GRGM distinctly improved retina damage via increasing the number of neurons, RGCs and axons in a concentration dependent manner. Meanwhile, GRGM obviously decreased the high level of MDA and the expression of oxidative stress-related proteins in retinas of DBA/2J mice, but promoted the expression of antioxidant proteins. Additionally, GRGM also significantly inhibited the protein expression of Bip and Chop, which were markers of endoplasmic reticulum stress-induced apoptosis. CONCLUSION: GRGM have obvious protective effects on RGCs in DBA/2J mice, and increase the number of RGCs and axons via inhibiting oxidative stress and endoplasmic reticulum stress.

GRGM-13 comprising 13 plant and animal products, inhibited oxidative stress induced apoptosis in retinal ganglion cells by inhibiting P2RX7/p38 MAPK signaling pathway.

OBJECTIVE: To determine the effectiveness of GRGM-13 on oxidative stress induced apoptosis of retinal ganglion cells (RGCs) and revealed its possible mechanism. MATERIALS AND METHODS: Caspase-3 activity, MDA level, and glutathione peroxidase level were detected by Caspase-3 assay kit, Lipid Peroxidation MDA Assay Kit, and Total Glutathione Peroxidase Assay Kit, respectively. Protein levels of Bax, Bcl-2, p-p38 and p38 were observed by Western Blot. Reactive oxygen species assay kit was used to determine intracellular ROS level. Apoptotic cells were measured by flow cytometry. RESULTS: GRGM-13 inhibited apoptosis of RGCs and ROS level in rat retinal tissue and RGC-5 cells, and the decrease degree strengthened with the increase of GRGM-13 concentration. In addition, ROS upregulated p-p38 expression, while GRGM-13 reversed this effect. We also found that p38 inhibitor SB202190 did not change L-glutamate (Glu) or H2O2-induced ROS level, while SB202190 inhibited apoptosis of RGC-5 cells. Finally, we observed that P2 × 7R agonist BzATP reversed the inhibition effect of GRGM-13 on RGC-5 cell apoptosis, ROS level and p-p38 expression, while si-P2 × 7R inhibited oxidative stress-induced phosphorylation of p38. CONCLUSION: GRGM-13 could inhibit oxidative stress-induced RGCs apoptosis via inhibiting P2RX7/p38 MAPK pathway, which revealed the possible mechanism of GRGM-13 on stress-induced RGCs apoptosis and provided new Chinese medicine for the treatment of glaucoma.

A Study of Preoperative Autologous Blood Donation Timing.

This study aims to determine the safe and effective autologous blood drawing time for preoperative autologous blood donation (PABDs) by comparing the outcome of two different schedules of PABDs. A total of 144 patients who underwent elective surgery (radical resection of digestive tract tumor, lumbarspinesurgery and Intracranial tumor resection) were retrospectively reviewed. 88 patients had donated autologous blood 2 days before the operation (group 1); 56 patients had donated autologous blood more than 3 days before the operation (group 2). Hb and Hct before the operation and on postoperative days one and three, allogeneic blood transfusions, total bleeding, postoperative length of stay, and length of stay were measured and compared. Hb at postoperative day one was lower in group 2 than in group 1 (P < 0.05). Furthermore, Hb in group 1 was higher at postoperative day one than at postoperative day three (P < 0.05). Differences in postoperative Hct, allogeneic blood transfusions, total bleeding and postoperative length of stay between these two groups were not statistically significant (P > 0.05)., The difference in the average number of postoperative hospitalization days between these two groups was not statistically significant (P > 0.05). The 2 days of PABD did not lead to any adverse recovery effect. It would be helpful to conduct preoperative autologous blood transfusions.

Optimal Factors of Diffusion Tensor Imaging Predicting Corticospinal Tract Injury in Patients with Brain Tumors.

OBJECTIVE: To identify the optimal factors in diffusion tensor imaging for predicting corticospinal tract (CST) injury caused by brain tumors. MATERIALS AND METHODS: This prospective study included 33 patients with motor weakness and 64 patients with normal motor function. The movement of the CST, minimum distance between the CST and the tumor, and relative fractional anisotropy (rFA) of the CST on diffusion tensor imaging, were compared between patients with motor weakness and normal function. Logistic regression analysis was used to obtain the optimal factor predicting motor weakness. RESULTS: In patients with motor weakness, the displacement (8.44 ± 6.64 mm) of the CST (p = 0.009), minimum distance (3.98 ± 7.49 mm) between the CST and tumor (p < 0.001), and rFA (0.83 ± 0.11) of the CST (p < 0.001) were significantly different from those of the normal group (4.64 ± 6.65 mm, 14.87 ± 12.04 mm, and 0.98 ± 0.05, respectively) (p = 0.009, p < 0.001, and p < 0.001). The frequencies of patients with the CST passing through the tumor (6%, p = 0.002), CST close to the tumor (23%, p < 0.001), CST close to a malignant tumor (high grade glioma, metastasis, or lymphoma) (19%, p < 0.001), and CST passing through infiltrating edema (19%, p < 0.001) in the motor weakness group, were significantly different from those of the patients with normal motor function (0, 8, 1, and 10%, respectively). Logistic regression analysis showed that decreased rFA and CST close to a malignant tumor were effective variables related to motor weakness. CONCLUSION: Decreased fractional anisotropy, combined with closeness of a malignant tumor to the CST, is the optimal factor in predicting CST injury caused by a brain tumor.

[Genotypes of adenoviruses in infants and young children with diarrhea].

OBJECTIVE: To investigate the prevalence of adenoviruses (AdV) and their genotypes in infants and young children with diarrhea. METHODS: A total of 380 children with diarrhea aged less than 3 years were enrolled. The genomic DNA was extracted from stool and PCR was used to detect AdV. Clone sequencing and genotyping were performed for DNA in AdV-positive specimens. RESULTS: AdV was detected in 24 out of 380 specimens, and the detection rate was 6.3% (24/380). A majority of children with positive AdV were aged 2-3 years. The viral sequence analysis of positive specimens showed that the detection rates of enteric AdV41 and non-enteric AdV were 4.2% (16/380) and 2.1% (8/380), respectively, and among the children with non-enteric AdV, there were 2 with AdV1, 2 with AdV2, 1 with AdV7, 2 with AdV12, and 1 with AdV31. CONCLUSIONS: Diarrhea caused by AdV is commonly seen in children aged 2-3 years, and AdV41 is the major predominant strain.

cAMP induction by ouabain promotes endothelin-1 secretion via MAPK/ERK signaling in beating rabbit atria.

Adenosine 3',5'-cyclic monophosphate (cAMP) participates in the regulation of numerous cellular functions, including the Na(+)-K(+)-ATPase (sodium pump). Ouabain, used in the treatment of several heart diseases, is known to increase cAMP levels but its effects on the atrium are not understood. The aim of the present study was to examine the effect of ouabain on the regulation of atrial cAMP production and its roles in atrial endothelin-1 (ET-1) secretion in isolated perfused beating rabbit atria. Our results showed that ouabain (3.0 µmol/L) significantly increased atrial dynamics and cAMP levels during recovery period. The ouabain-increased atrial dynamics was blocked by KB-R7943 (3.0 µmol/L), an inhibitor for reverse mode of Na(+)-Ca(2+) exchangers (NCX), but did not by L-type Ca(2+) channel blocker nifedipine (1.0 µmol/L) or protein kinase A (PKA) selective inhibitor H-89 (3.0 µmol/L). Ouabain also enhanced atrial intracellular cAMP production in response to forskolin and theophyline (100.0 µmol/L), an inhibitor of phosphodiesterase, potentiated the ouabain-induced increase in cAMP. Ouabain and 8-Bromo-cAMP (0.5 µmol/L) markedly increased atrial ET-1 secretion, which was blocked by H-89 and by PD98059 (30 µmol/L), an inhibitor of extracellular-signal-regulated kinase (ERK) without changing ouabain-induced atrial dynamics. Our results demonstrated that ouabain increases atrial cAMP levels and promotes atrial ET-1 secretion via the mitogen-activated protein kinase (MAPK)/ERK signaling pathway. These findings may explain the development of cardiac hypertrophy in response to digitalis-like compounds.

[Study on the Spectrum Research on the Process of Oil Shale Pyrolysis].

Spectral analysis is an important and unique advantageous method for the analysis of matter's structure and composition. Aiming to discuss the change characteristic and evolution mechanism of mineral structure of oil shale, kerogen and sime-coke from oil shale pyrolysis under different temperature, the oil shale sample was obtained from Yaojie located in Gansu province, and the oil shale after pyrolysis experiments and acid washing were investigated and analyzed in detail withpolarizing microscope, Fourier transform spectroscopy (FTIR), X-Ray diffraction (XRD) and scanning electron microscope (SEM). The result shows that the mainly minerals of oil shale include quartz, clay and pyrite; kerogen is randomly distributed as mainly strip-shaped or blocky in inorganic minerals. The metamorphic degree of kerogen is higher, and rich in aliphatic structures and aromatic structures. Experiments of oil shale pyrolysis(temperature: 300～1 000 ℃, heating rate: 10 ℃·min-1) with temperature increasing, the composition of mineral begins to dissolve, kaolinite turning into metakaolinite with dehydration at 300 ℃, clay minerals such as kaolinite and montmorillonite completely turn into metakaolinite at 650 ℃. The silica-alumina spinel and amorphous SiO2, generated from the decomposition of metakaolinite at 1 000 ℃, and the amorphous SiO2, tends to react with iron mineral to form relative low melting point mixture on the semi-coke surfaces, such as FeO­Al2O3­SiO2. kerogen break down with increasing temperature, the infrared spectra intensity of C­H band of aliphatic and aromatic is reduced, while the intensity of C­C band aromatic is increased, and more carbonaceous residue as gully-shaped that remains in the mineral matrix after pyrolysis. These results are important for both the study of structure evolution of kerogen and minerals on the process of oil shale pyrolysis and will benefit for the subsequent processing and utilization of shale oil resource.

Decreased miR-187 induces retinal ganglion cell apoptosis through upregulating SMAD7 in glaucoma.

BACKGROUND: Retinal ganglion cells (RGCs) are commonly experienced optic nerve diseases including glaucoma-induced injury that results in decrease of cell survival. However, the underlying mechanism remains to be elaborated. This present study was to focus on the miR-187 and Transforming growth factor-ß (TGF-ß) signal and investigated their roles in RGCs apoptosis and proliferation. METHODS: RGC-5 retinal ganglion cell line was chose in present study and subjected to miR-187 mimic or inhibitor transfection. Cell apoptosis was evaluated using flow cytometry-based Annexin V-PI assay. Cell proliferation was examined using CCK-8. Protein levels of Smad2/3/7 were determined using western blotting. RESULTS: miR-187 negatively regulated cell survival via inhibiting cell apoptosis and promoting cell proliferation. We observed that alteration expression of miR-187 is closely related to phosphorylation levels of Smad2 and Smad3. This correlation is associated with down-regulation of Smad7 induced by miR-187 via targeting Smad7 3'-UTR. From result of co-transfection of Smad7-plasmid and miR-187 mimic or siSmad7 and miR-187 inhibitor, we concluded that cell proliferation and apoptosis was mediated by miR-187/Smad7 axis. CONCLUSION: In summary, cell internal signal transduction, miR-187 regulating Smad7 expression, plays a vital role in retinal ganglion cell survival.

Progress and challenges in the use of latent HIV-1 reactivating agents.

Highly active antiretroviral therapy (HAART) can effectively suppress the replication of human immunodeficiency virus-1 (HIV-1) and block disease progression. However, chronic HIV-1 infection remains incurable due to the persistence of a viral reservoir, including the transcriptionally silent provirus in CD4(+) memory T cells and the sanctuary sites that are inaccessible to drugs. Reactivation and the subsequent elimination of latent virus through virus-specific cytotoxic effects or host immune responses are critical strategies for combating the disease. Indeed, a number of latency reactivating reagents have been identified through mechanism-directed approaches and large-scale screening, including: (1) histone deacetylase inhibitors (HDACi); (2) cytokines and chemokines; (3) DNA methyltransferase inhibitors (DNMTI); (4) histone methyltransferase inhibitors (HMTI); (5) protein kinase C (PKC) activators; (6) P-TEFb activators; and (7) unclassified agents, such as disulfram. They have proved to be efficacious in latent cell line models and CD4(+) T lymphocytes from HIV-1-infected patients. This review comprehensively summarizes the recent progress and relative challenges in this field.

Decreased activation of cingulo-frontal-parietal cognitive/attention network during an attention-demanding task in patients with chronic low back pain.

INTRODUCTION: Attention deficits have been repeatedly reported via neuropsychological assessment in previous literature in patients with chronic low back pain (CLBP). However, there are few functional neuroimaging studies of patients with CLBP during attention processing, and the exact underlying neural mechanisms are yet to be elucidated. METHODS: We used functional magnetic resonance imaging (fMRI) to measure the function of the cingulo-frontal-parietal (CFP) cognitive/attention network while performing a multi-source interference task (MSIT) in patients with CLBP. Thirty-six patients with CLBP and 36 healthy controls were included in this study. The fMRI data were analyzed with the FSL-FEAT software. RESULTS: Our results indicated that patients with CLBP showed significantly less activation in the CFP network including the right dorsolateral prefrontal cortex, the dorsal anterior cingulate cortex, and bilateral superior parietal cortex during attention-demanding (MSITinterference > MSITcontrol) trials compared to the healthy controls. A significant negative correlation was found between the scores of the visual analog scale for pain and activation of the right prefrontal cortex during performing the MSIT in patients with CLBP. CONCLUSION: Our study provides in vivo imaging evidence of abnormal CFP network function during attention-demanding condition in patients with CLBP, which might reflect partly an adaptation/maladaptation of the brain to the chronic pain states.

Synergistic killing effect of arsenic trioxide combined with curcumin on KG1a cells / 中国实验血液学杂志

This study was aimed to explore the effect of arsenic trioxide combined with curcumin on proliferation and apoptosis of KG1a cells and its potential mechanism. The cell survival rate was mesured by MTT; colony formation capacity was examined by methylcellulose colony formation test; flow cytometry was used to analyse the cell surface molecules, cell apoptosis rate and cell cycle; the cell morphology was observed with Wright-Giemsa staining and the protein expression of BCL-2, BAX, PARP was detected by Western blot. The results showed that the phenotype of KG1a cells was CD34(+)CD38(-), while the phenotype of HL-60 cell was CD34(+)CD38(+). The former possessed a stronger colony ability than the latter. Effect of curcumin and arsenic trioxide alone on cell proliferation and inhibition was in dose-dependent manner. Compared with single drug-treatment group, the cell survival rate and colony number were lower, and the apoptosis rate was higher in combined drug-treatment group. Protein expression of BCL-2 and PARP was upregulated, while the protein expression of PARP was downregulated in the combined treatment group. It is concluded that compared with HL-60 cells, KG1a cells are the earlier leukemia stem/progenitor cells. Arsenic trioxide combined with curcumin can effectively inhibit the KG1a cell proliferation and induce apoptosis, which may be associated with the downregulation of BCL-2 and PARP protein expression and the upregulation of BAX protein expression.

Effect of honokiol on proliferation and apoptosis in HL-60 cells and its potential mechanism / 中国实验血液学杂志

This study was aimed to investigate the effect of Honokiol (HNK) on proliferation and apoptosis of acute myeloid leukemia HL-60 cells and its potential mechanism. Inhibitory effect of HNK on the HL-60 cell proliferation was detected by MTT assay. Flow cytometry was used to detect the change of cell cycle and AnnexinV/PI staining was used to detect apoptosis. Western blot was applied to analyze the cell cycle protein (cyclins), cyclin-dependent kinase (CDK), P53, P21, P27, BCL-2, BCL-XL, Bax, caspase-3/9 and proteins for MAPK signal pathway. The results showed that HNK could inhibit the proliferation of HL-60 cells in time- and dose dependent ways. HNK arrested HL-60 cells in G0/G1 phase, and S phase cells decreased significantly (P < 0.05). The expression of cyclin D1, cyclin A, cyclin E and CDK2/4/6 were significantly down-regulated (P < 0.05), the expression of P53 and P21 was significantly upregulated after treating for 24 h with HNK (P < 0.05). After 24 h treatment with HNK, HL-60 cell apoptosis increased significantly with the upregulation of activated caspase-3, -9, BAX expression and the downregulation of BCL-2, BCL-XL expression. The MAPK subfamily, P38 and JNK were not significantly changed, but the expression of MEK1/2-ERK1/2 was significantly downregulated (P < 0.05). It is concluded that HNK arrestes the cells at G0/G1 phase and induces HL-60 cell apoptosis through the intervention of MEK1/2-ERK1/2 signaling pathway.

MAPK and PI3K pathways regulate hypoxia-induced atrial natriuretic peptide secretion by controlling HIF-1 alpha expression in beating rabbit atria.

Mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K) signaling pathways are pivotal and intensively studied signaling pathways in hypoxic conditions. However, the roles of MAPK and PI3K in the regulation of hypoxia-induced atrial natriuretic peptide (ANP) secretion are not well understood. The purpose of the present study was to investigate the mechanism by which the MAPK/ERK (extracellular signal-regulated kinase) and PI3K signaling pathways regulate the acute hypoxia-induced ANP secretion in isolated beating rabbit atria. An acute hypoxic perfused beating rabbit atrial model was used. The ANP levels in the atrial perfusates were measured by radioimmunoassay, and the hypoxia-inducible factor-1α (HIF-1α) mRNA and protein levels in the atrial tissue were determined by RT-PCR and Western blot. Acute hypoxia significantly increased ANP secretion and HIF-1α mRNA and protein levels. Hypoxia-induced ANP secretion was markedly attenuated by the HIF-1α inhibitors, rotenone (0.5µmol/L) and CAY10585 (10µmol/L), concomitantly with downregulation of the hypoxia-induced HIF-1α mRNA and protein levels. PD098059 (30µmol/L) and LY294002 (30µmol/L), inhibitors of MAPK and PI3K, markedly abolished the hypoxia-induced ANP secretion and atrial HIF-1α mRNA and protein levels. The hypoxia-suppressed atrial dynamics were significantly attenuated by PD098059 and LY294002. Acute hypoxia in isolated perfused beating rabbit atria, markedly increased ANP secretion through HIF-1α upregulation, which was regulated by the MAPK/ERK and PI3K pathways. ANP appears to be part of the protective program regulated by HIF-1α in the response to acute hypoxic conditions.

[Seasonal variation of blood pressure and related factors in Chinese adults: a survey of over 50 000 people in Suzhou, China].

OBJECTIVE: Seasonal variation in blood pressure had been observed in several studies on Western populations, but uncertainty remains about the strength of the relationship in other populations and the extent to which it was modified by other factors. METHODS: This study was based on cross-sectional data from the China Kadoorie Biobank study with 53 260 men and women from the Suzhou area involved. Linear regression model was used to analyze the association of blood pressure with outdoor temperature-overall and in various subgroups. RESULTS: Blood pressure varied with the seasons, ascending in winter and descending in summer. The difference in systolic blood pressure (SBP) between summer and winter was 8.8 mm Hg in men and 7.0 mm Hg in women. SBP was inversely correlated with outdoor temperature, especially above 10°C, with every 10°C colder temperature causing 6.1 mm Hg increase of SBP. The seasonal variation in SBP was more obviously seen in older people and in those with lower body mass index. CONCLUSION: Blood pressure was strongly and inversely associated with outdoor temperature in the population in Suzhou area. Seasonal variation of blood pressure should be considered when the hypertension screening programs, clinical management and data management on hypertensive patients.