NOX2-mediated reactive oxygen species are double-edged swords in focal cerebral ischemia in mice.

BACKGROUND: Reactive oxygen species (ROS) often promote acute brain injury after stroke, but their roles in the recovery phase have not been well studied. We tested the hypothesis that ROS activity mediated by NADPH oxidase 2 (NOX2) contributes to acute brain injury but promotes functional recovery during the delayed phase, which is linked with neuroinflammation, autophagy, angiogenesis, and the PI3K/Akt signaling pathway. METHODS: We used the NOX2 inhibitor apocynin to study the role of NOX2 in brain injury and functional recovery in a middle cerebral artery occlusion (MCAO) stroke mouse model. Infarct size, neurological deficits and behavior were evaluated on days 3, 7, 10 and 14 after reperfusion. In addition, dynamic NOX2-induced ROS levels were measured by dihydroethidium (DHE) staining. Autophagy, inflammasomes, and angiogenesis were measured by immunofluorescence staining and western blotting. RNA sequencing was performed, and bioinformatics technology was used to analyze differentially expressed genes (DEGs), as well as the enrichment of biological functions and signaling pathways in ischemia penumbra at 7 days after reperfusion. Then, Akt pathway-related proteins were further evaluated by western blotting. RESULTS: Our results showed that apocynin injection attenuated infarct size and mortality 3 days after stroke but promoted mortality and blocked functional recovery from 5 to 14 days after stroke. DHE staining showed that ROS levels were increased at 3 days after reperfusion and then gradually declined in WT mice, and these levels were significantly reduced by the NOX2 inhibitor apocynin. RNA-Seq analysis indicated that apocynin activated the immune response under hypoxic conditions. The immunofluorescence and western blot results demonstrated that apocynin inhibited the NLRP3 inflammasome and promoted angiogenesis at 3 days but promoted the NLRP3 inflammasome and inhibited angiogenesis at 7 and 14 days after stroke, which was mediated by regulating autophagy activation. Furthermore, RNA-Seq and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that apocynin injection resulted in PI3K-Akt signaling pathway enrichment after 7 days of MCAO. We then used an animal model to show that apocynin decreased the protein levels of phosphorylated PI3K and Akt and NF-κB p65, confirming that the PI3K-Akt-NF-κB pathway is involved in apocynin-mediated activation of inflammation and inhibition of angiogenesis. CONCLUSIONS: NOX2-induced ROS production is a double-edged sword that exacerbates brain injury in the acute phase but promotes functional recovery. This effect appears to be achieved by inhibiting NLRP3 inflammasome activation and promoting angiogenesis via autophagy activation.

Changes in cognitive and behavioral function in patients with cerebral small vessel disease and their correlation with serum homocysteine and cystatin C levels / 中国基层医药

Objective:To investigate the changes in cognitive and behavioral function in patients with cerebral small vessel disease and their correlation with serum homocysteine (Hcy) and cystatin C (CysC) levels.Methods:Ninety-four patients with cerebral small vascular disease who received treatment in Zhejiang Xin'an International Hospital from March 2019 to March 2021 were included in the observation group. An additional 80 healthy controls who concurrently received physical examination were included in the control group. The Mini-Mental State Scale (MMSE) and the Montreal Assessment Scale (MoCA) were used to evaluate cognitive function. The activity of daily living (ADL) was used to evaluate behavioral function. Enzyme-linked immunosorbent assay was used to measure serum Hcy and CysC levels. MMSE score, MoCA score, ADL score, serum Hcy and CysC levels were compared between the two groups. The receiver operating characteristic (ROC) curve was used to analyze the sensitivity and specificity of serum Hcy and CysC levels in the diagnosis of cerebral small vessel disease. Pearson correlation analysis was performed to analyze the correlation between serum Hcy and CysC levels and cognitive behavioral function.Results:MMSE score, MoCA score, and ADL score in the observation group were (21.21 ± 2.87) points, (20.18 ± 3.25) points, and (34.32 ± 5.45) points, which were significantly lower than (28.23 ± 1.02) points, (28.45 ± 0.89) points and (76.35 ± 8.29) points in the control group ( t = 20.78, 22.05, 40.03, all P < 0.05). Serum Hcy and CysC in the observation group were (16.28 ± 2.97) μmol/L and (1.21 ± 0.23) mg/L, which were significantly higher than (8.35 ± 1.76) μmol/L and (0.56 ± 0.12) mg/L in the control group ( t = 20.95, 22.77, both P < 0.05). ROC curve analysis showed that the sensitivity and specificity of serum Hcy in diagnosing cerebral small vessel disease were 85.29% and 53.85%, respectively; the sensitivity and specificity of serum CysC in diagnosing cerebral small vessel disease were 81.54% and 41.38%, respectively. Pearson correlation analysis revealed that serum Hcy level was linearly negatively correlated with MMSE score, MoCA score, and ADL score ( r = -0.79, -0.68, -0.71, all P < 0.05); serum CysC level was linearly negatively correlated with MMSE score, MoCA score, and ADL score ( r = -0.67, -0.75, -0.78, P < 0.05). Conclusion:The cognitive and behavioral function of patients with cerebral small vessel disease are decreased, and serum Hcy and CysC levels are increased. Serum Hcy and CysC levels are closely related to the cognitive and behavioral function of patients with cerebral small vessel disease.

Self-suppression of common-mode noises of the different fiber optic interferometric accelerometers.

This study proposes two new fiber optic interferometric accelerometers with the utilization of the push-pull structure, one is based on the principle of triple low-reflectivity fiber Bragg gratings, and the other is based on the 1x3 unbalanced Michelson interferometer. The proposed accelerometers are capable of suppressing the common-mode noises (CMNs) by themselves without additional reference accelerometers, and therefore reducing the volume and the cost of the sensing system. Besides, the accelerometers can also suppress the sensor noises caused by the environment, and therefore show better CMNs suppression effect than the traditional method of using the reference accelerometer. The two accelerometers are experimentally verified and show respectively an improvement of 33 dB and 28 dB in CMNs suppression at 100 Hz. Both presented fiber optic accelerometers show huge advantages for the large-scale quasi-distributed oil and gas reservoir monitoring applications.

Worsened brain edma and the level of serum HMGB1 and S100B of IL-4 knockout mice after traumatic brain injury / 中华行为医学与脑科学杂志

Objective To investigate the changes of brain edma and expression of blood high mobil-ity group box 1(HMGB1) and calcium binding protein S100B after traumatic brain injury (TBI) in IL-4 knockout (IL-4 KO) mice,and to explore the effects of IL-4 on traumatic brain injury. Methods Twenty male wild type ( WT) or twenty male IL-4 KO BALB/cJ mice were randomly divided into WT sham TBI group,WT TBI group,IL-4 KO sham TBI group and IL-4 KO TBI group(n=10 in each group).The model of traumatic brain injury was established by the free falling body epidural impact method,then the brain water content was measured. The expression of aquaporin-4 ( APQ4) and HMGB1 in injured brain of each group was detected by Western blot,and the concentration of HMGB1 and S100B in serum was detected by ELISA assay. Results ( 1 ) The brain water content of injured lateral brain of BALB/cJ mice with IL-4 gene knockout was significantly higher than that of wild type mice with brain injury model (WT group: (80.03± 0.35)％;IL-4 KO group:(81.93±0.41)％;P<0.05).(2) The Western blot showed that the expression of AQP4 and HMGB1 in brain tissue of BALB/cJ mice with IL-4 gene knockout was significantly higher than those in wild type mice after traumatic brain injury. ( 3) The results of ELISA showed that the levels of HMGB1 and S100B in the serum of IL-4 knockout BALB/cJ mice were significantly higher than those of wild type mice (HMGB1:WT group:(9.21±0.74)ng/ml;IL-4 gene knock-out group:(13.39±1.33)ng/ml,P<0.05;S100B protein:WT group:(11.11±0.84)pg/ml;IL-4 KO group: (18.11±2.02)pg/ml,P<0.05 ). Conclusion The brain tissue water content and the expression of APQ4 are increased in IL-4 KO TBI mice.The expression of HMGB1 in brain issue and serum and S100B in serum are also up-regulated.

Clinical value of acoustic radiation force impulse elastography in differential diagnosis of focal liver lesions / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the clinical value of acoustic radiation force impulse (ARFI) elastography in the differential diagnosis of focal liver lesions.</p><p><b>METHODS</b>ARFI elastography was performed for 169 lesions from 163 patients with focal liver lesions and 15 healthy volunteers, and the virtual touch tissue imaging (VTI) findings and measured value of shear wave velocity (SWV) of liver lesions were obtained and compared between groups. The t-test was applied for comparison of means between two groups; the one-way analysis of variance was applied for comparison of means between multiple groups, and the Student-Newman-Keuls test was applied for further comparison between any two groups.</p><p><b>RESULTS</b>Benign focal liver lesions were stiffer or softer than or had the same stiffness as the surrounding liver parenchyma. These lesions had a uniform texture, and the ratio between their diameters on elastographic images and two-dimensional images was close to 1. The typical VTI finding of hemangioma lesions was"honeycomb"pattern. Most malignant focal liver lesions were stiffer than the surrounding liver parenchyma, and the ratio between their diameters on elastographic images and two-dimensional images was greater than 1. The typical VTI finding of metastatic lesions was"bull's eye"sign. With a measured SWV of 2.08 m/s as the diagnostic threshold for malignant liver lesions, its sensitivity, specificity, and accuracy were 90.3%, 76.9%, and 84.2%, respectively. Poorly differentiated hepatocellular carcinoma (HCC) showed a significant increase in stiffness compared with moderately differentiated HCC (t = 5.319, P = 0.025) and well-differentiated HCC (t = 6.372, P = 0.011).</p><p><b>CONCLUSION</b>ARFI elastography can reflect changes in the stiffness of focal liver lesions accurately, and is useful for the differential diagnosis of benign and malignant focal liver lesions.</p>

Effects of Ultra-filtration Extract from Angelicae Sinensis Radix and Hedysarum Polybotrys on Expressions of HSP70 and eNOS in H2O2-induced Endothelial Cell Apoptosis / 中国中医药信息杂志

Objective To investigate the effects of ultra-filtration extract from the mixture of Angelicae Sinensis Radix and Hedysarum Polybotrys (UFE-AH) on the expressions of HSP70 and eNOS in H2O2-induced endothelial cell apoptosis. Methods H2O2 induced ECV-304 cell apoptosis to prepare models. The experiment was divided into normal control group, model group, simple medicine group, medicine intervention group, and all treatment groups received relevant medicine for intervention. Flow cytometry (FCM) was used to detect apoptosis and concentration of intracellular Ca2+;RT-PCR was used to detect the mRNA expression of HSP70 and eNOS;Western blot was used to detect the expression of HSP70 protein;Nitrale reduetase and spectrophotometric method were employed to detect the content of NO. Results Compared with normal control group, cell apoptosis rate, concentration of intracellular Ca2+, and expression of HSP70 increased significantly in model group (P<0.05);gene expression of eNOS mRNA and content of NO decreased (P<0.05). Compared with model group, cell apoptosis rate and concentration of intracellular Ca2+dropped in medicine intervention group (P<0.05);expressions of HSP70, eNOS mRNA and content of NO increased (P<0.05). Conclusion UFE-AH can confront H2O2-induced cell apoptosis H2O2 of ECV-304 human umbilical vein endothelial by increasing the expressions of HSP70 and eNOS and content of NO, and reducing the intracellular calcium overload.

Cow placenta extract promotes murine hair growth through enhancing the insulin - like growth factor-1.

BACKGROUND: Hair loss is seen as an irreversible process. Most research concentrates on how to elongate the anagen, reduce the negative factors of obstructing hair growth and improve the hair number and size. AIM: In our experiment, we tried to prove that the cow placenta extract can promote hair growth by elongating hair shaft and increasing hair follicle number. MATERIALS AND METHODS: Cow placenta extract (CPE), water and minoxidil applied separately on the back of depilated B57CL/6 mice for the case, negative and positive control respectively. We checked the proliferation of cells which are resident in hair sheath, and the expression of a few growth factors which stimulate hair growth. RESULTS: Result shows that placenta extract more efficiently accelerates cell division and growth factor expression, by raising the insulin-like growth factor (IGF-1) mRNA and protein level to increase HF size and hair length. CONCLUSIONS: The extract is not a purified product; so, it is less effective than minoxidil, which is approved by the US FDA for the treatment of male pattern baldness. If refinement is done, the placenta extract would be a good candidate medicine for hair loss.