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.

[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.

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.

[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.

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.

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.

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.

Association of daily tar and nicotine intake with incident myocardial infarction: results from the population-based MONICA/KORA Augsburg Cohort Study 1984-2002.

BACKGROUND: Cigarette smoking has been shown to be one of the most important risk factors for cardiovascular diseases. However, little is known about cumulative effects of daily tar and nicotine intake on the risk of incident myocardial infarction (MI) so far. To bridge this gap, we conducted an analysis in a large prospective study from Southern Germany investigating associations of daily tar and nicotine intake with an incident MI event. METHODS: The study was based on 4,099 men and 4,197 women participating in two population-based MONICA Augsburg surveys between 1984 and 1990 and followed up within the KORA framework until 2002. During a mean follow-up of 13.3 years, a number of 307 men and 80 women developed an incident MI event. Relative risks were calculated as hazard ratios (HRs) estimated by Cox proportional hazards models adjusted for cardiovascular risk factors. RESULTS: In the present study, male regular smokers consumed on average more cigarettes per day than female regular smokers (20 versus 15) and had a higher tar and nicotine intake per day. In men, the MI risk compared to never-smokers increased with higher tar intake: HRs were 2.24 (95% CI 1.40-3.56) for 1-129 mg/day, 2.12 (95% CI 1.37-3.29) for 130-259 mg/day and 3.01 (95% CI 2.08-4.36) for ≥ 260 mg/day. In women, the corresponding associations were comparable but more pronounced for high tar intake (HR 4.67, 95% CI 1.76-12.40). Similar associations were observed for nicotine intake. CONCLUSIONS: The present study based on a large population-based sample adds important evidence of cumulative effects of tar and nicotine intake on the risk of incident MI. Even low or medium tar and nicotine intake revealed substantial risk increases as compared to never-smokers. Therefore, reduction of tar and nicotine contents in cigarettes cannot be seen as a suitable public health policy in preventing myocardial infarction.

Epidemiology of chronic kidney disease: results from a population of older adults in Germany.

OBJECTIVE: To determine prevalences and stages of chronic kidney disease (CKD), and evaluate association of CKD with related covariables in a large population of older adults. METHODS: This cross-sectional analysis included 9806 participants of a general health check-up aged 50-74 years in Germany. We performed multivariate analysis to identify association of CKD with related covariables. Partial spearman correlations of eGFR with related biomarkers were calculated. RESULTS: Overall, 17.4% of subjects had CKD. Prevalences of stages 1, 2, 3, 4/5 CKD were 4.6%, 4.7%, 17.0% and 0.4%, respectively. Prevalence of CKD increased with age and peaked in age 70-74 years with 23.9%. In multivariable analysis of older age, female, self-reported history of cardiovascular diseases, diabetes and statin usage were independently associated with increased risk for CKD. Significant correlations were found between eGFR and serum cystatin C (-0.28), C-reactive protein (-0.04), fasting glucose (0.12), HbA(1c) (-0.06), total cholesterol (-0.32), and triglycerides (-0.07) after adjustment for covariates. CONCLUSIONS: This study shows a high prevalence of CKD among older adults. It highlights the association of eGFR with history of cardiovascular diseases, glycemic markers, and cardiovascular risk factors and may point to further possible targets in early prevention of CKD.

Prevalence of chronic kidney disease in population-based studies: systematic review.

BACKGROUND: Chronic kidney disease (CKD) is becoming a major public health problem worldwide. This article reviews the published evidence of prevalence of CKD in population-based study samples that used the standardized definition from the Kidney Disease Outcomes Quality Initiative of the National Kidney Foundation (K/DOQI) practice guideline, and particularly focus on performance of serum-creatinine based equations for GFR estimation. We provide a summary of available data about the burden of CKD in various populations. METHODS: We performed a systematic review of available published data in MEDLINE. A combination of various keywords relevant to CKD was used in this research. Related data of included studies were extracted in a systematic way. RESULTS: A total of 26 studies were included in this review. The studies were conducted in different populations, and the number of study participants ranged from 237 to 65181. The median prevalence of CKD was 7.2% in persons aged 30 years or older. In persons aged 64 years or older prevalence of CKD varied from 23.4% to 35.8%. Importantly, the prevalence of CKD strongly depended on which estimating equations were used. The Modification of Diet in Renal Disease Study (MDRD) equation was likely to be preferred in recent epidemiological studies compared to the adjusted Cockcroft-Gault (CG) equation. CONCLUSION: Worldwide, CKD is becoming a common disease in the general population. Accurately detecting CKD in special groups remains inadequate, particularly among elderly persons, females or other ethnic groups such as Asians.

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.

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.

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.

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.

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.

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.

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.