Exosomal HSP90 induced by remote ischemic preconditioning alleviates myocardial ischemia/reperfusion injury by inhibiting complement activation and inflammation.

BACKGROUND/AIMS: The activation of the complement system and subsequent inflammatory responses are important features of myocardial ischemia/reperfusion (I/R) injury. Exosomes are nanoscale extracellular vesicles that play a significant role in remote ischemic preconditioning (RIPC) cardioprotection. The present study aimed to test whether RIPC-induced plasma exosomes (RIPC-Exo) exert protective effects on myocardial I/R injury by inhibiting complement activation and inflammation and whether exosomal heat shock protein 90 (HSP90) mediates these effects. METHODS: Rat hearts underwent 30 min of coronary ligation followed by 2 h of reperfusion. Plasma exosomes were isolated from RIPC rats and injected into the infarcted myocardium immediately after ligation. Sixty rats were randomly divided into Sham, I/R, I/R + RIPC-Exo (50 µg/µl), and RIPC-Exo + GA (geldanamycin, 1 mg/kg, administration 30 min before ligation) groups. Cardiomyocyte apoptosis, the release of myocardial markers (LDH, cTnI and CK-MB), infarct size, the expression of HSP90, complement component (C)3, C5a, c-Jun N-terminal kinase (JNK), interleukin (IL)-1ß, tumor necrosis factor (TNF)-alpha and intercellular adhesion molecule -1 (ICAM-1) were assessed. RESULTS: RIPC-Exo treatment significantly reduced I/R-induced cardiomyocyte apoptosis, the release of myocardial markers (LDH, cTnI and CK-MB) and infarct size. These beneficial effects were accompanied by decreased C3 and C5a expression, decreased inflammatory factor levels (IL-1ß, TNF-α, and ICAM-1), decreased JNK and Bax, and increased Bcl-2 expression. Meanwhile, the expression of HSP90 in the exosomes from rat plasma increased significantly after RIPC. However, treatment with HSP90 inhibitor GA significantly reversed the cardioprotection of RIPC-Exo, as well as activated complement component, JNK signalling and inflammation, indicating that HSP90 in exosomes isolated from the RIPC was important in mediating the cardioprotective effects during I/R. CONCLUSION: Exosomal HSP90 induced by RIPC played a significant role in cardioprotection against I/R injury, and its function was in part linked to the inhibition of the complement system, JNK signalling and local and systemic inflammation, ultimately alleviating I/R-induced myocardial injury and apoptosis by the upregulation of Bcl-2 expression and the downregulation of proapoptotic Bax.

Role of CT perfusion imaging in patients with variously differentiated gastric adenocarcinoma.

PURPOSE: To explore the characteristics of variously differentiated gastric cancers on computed tomography (CT) perfusion imaging, including specific perfusion parameter values, and potential clinical applications in the prognosis assessment of gastric cancer. MATERIALS AND METHODS: Fifty patients with gastric cancer confirmed by gastroscope pathology were studied prospectively using CT perfusion imaging examinations on a 64-slice spiral CT scanner. The acquired volume data were used for calculations, mapping, and analysis by using an abdominal tumor perfusion protocol (deconvolution method) in the CT perfusion software package to measure 4 parameters: blood flow (BF), blood volume (BV), mean transit time (MTT), and the permeability surface (PS) area product. The different differentiated Gastric cancers with CT perfusion values were divided into 3 groups: well-differentiated, moderately differentiated and poorly differentiated gastric adenocarcinoma, and compared statistically with one another by statistical software. RESULTS: The mean perfusion values of 10 patients with well-differentiated gastric adenocarcinoma were as follows: BF, 75.28 ± 6.81 mL/100 g/min; BV, 9.01 ± 0.94 mL/100 g; MTT, 9.89 ± 1.65 s; and PS, 10.05 ± 0.71 mL/100 g/min. The mean perfusion values of 24 patients with moderately differentiated gastric adenocarcinoma were as follows: BF, 110.01 ± 31.90 mL/100 g/min; BV, 18.18 ± 5.62 mL/100 g; MTT, 9.81 ± 3.69 s; and PS, 40.08 ± 15.82 mL/100 g/min. The mean perfusion values of 16 patients with poorly differentiated gastric adenocarcinoma were as follows: BF, 138.59 ± 38.09 mL/100 g/min; BV, 21.08 ± 4.11 mL/100 g; MTT, 9.47 ± 1.80 s; and PS, 57.50 ± 13.28 mL/100 g/min. Comparing the 3 groups, differences between the well-differentiated group and the moderate differentiation group were all statistically significant for BF, BV, and PS (p < 0.05, respectively), differences between the well-differentiated group and the poor differentiation group were all statistically significant for BF, BV, and PS (p < 0.05,respectively) as well; While MTT value showed no statistical difference among the 3 groups (p > 0.05). CONCLUSION: Stomach CT perfusion imaging is a functional imaging technology from the perspective of hemodynamics with potential clinical applications. The BF, BV and PS values could serve as indicators of the degree of malignancy and aid in prognostic assessment of gastric cancer.

[Multi-spectral thermometry based on radiation measurement within a finite solid-angle].

Based on Planck's law, the surface temperature of an object can be determined by measurement of emitted radiation. The equation for monochromatic radiation thermometry within a finite solid-angle was deduced, and it was found that if the surface temperature and spectral emissivity can be solved at the same time, the specific radiation measurement conditions for multi-spectral thermometry should be generally met that the radiation measurement should be implemented within an infinitesimal solid-angle or within a finite solid-angle only for a perfect diffuser. When the directional spectral emissivity modeled by finite polynomial series is employed and proper mathematical transformation is used, a universal equation for monochromatic radiation thermometry is obtained. So the restrictions in radiation measurement can be got rid of, but spectral emissivity may not be solved simultaneously. Multi-solution problem was preliminarily investigated, and so a solution was put forward that the channel number should be more than the number of the variables to be solved and the nonlinear least squares method should be used.

Network pharmacology and molecular docking-based investigation on traditional Chinese medicine Astragalus membranaceus in oral ulcer treatment.

To analyze the mechanism of Astragalus membranaceus (AM) in molecular level in the oral ulcer (OU) treatment with reference to network pharmacology. Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform database was used in screening the AM active components and AM action targets; GeneCards database was used to screen OU targets; the common target were screened by Venny online tool; Cytoscape software was applied to construct the target gene regulation map of AM active components; STRING database was used to construct the protein-protein interaction network and the key targets were screened as per degree value; gene ontology enrichment and KEGG pathway enrichment of interactive genes were calculated through David database. There were 17 active ingredients and 429 target spots in Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform database. There are 606 target genes for OU in GeneCards database. There are 67 common targets, including 10 key targets: IL10, IL6, TNF, IL1B, CXCL8, CCL2, TLR4, IL4, ICAM1, and IFNG. It involves 30 gene ontology terms and 20 KEGG signal channels. The molecular docking results showed that quercetin and kaempferol had a good binding activity with IL6, IL1B, TNF, and CCL2. Network pharmacological analysis shows that AM can regulate multiple signal pathways through multiple targets to treat OU.

Quantitative multivoxel proton MR spectroscopy study of brain metabolites in patients with amnestic mild cognitive impairment: a pilot study.

INTRODUCTION: The purpose of this study is to investigate brain metabolic changes in patients with amnestic mild cognitive impairment (aMCI) using multivoxel proton MR spectroscopy ((1)H-MVS). METHODS: Fourteen aMCI patients and fifteen healthy control subjects participated in this experiment. All MR measurements were acquired using a 1.5-T GE scanner. (1)H-MVS point resolved spectroscopy (2D PROBE-CSI PRESS) pulse sequence (TE = 35 ms; TR = 1,500 ms; phase × frequency, 18 × 18) was used for acquiring MRS data. All data were post-processed using Spectroscopy Analysis by General Electric software and linear combination of model (LCModel). The absolute concentrations of N-acetylaspartate (NAA), choline (Cho), myoinositol (MI), creatine (Cr), and the metabolite ratios of NAA/Cr, Cho/Cr, MI/Cr, and NAA/MI were measured bilaterally in the posterior cingulate gyrus (PCG), inferior precuneus (Pr), paratrigonal white matter (PWM), dorsal thalamus (DT), and lentiform nucleus (LN). RESULTS: Patients with aMCI displayed significantly lower NAA levels in the bilateral PCG (p < 0.01), PWM (p < 0.05), and left inferior Pr (p < 0.05). The metabolite ratio of NAA/MI was decreased in the bilateral PCG (p < 0.01) and PWM (p < 0.05) and in the left DT (p < 0.01). NAA/Cr was decreased in the left PCG (p < 0.01), DT (p < 0.05), right PWM (p < 0.05), and LN (p < 0.05). However, MI/Cr was elevated in the right PCG (p < 0.01) and left PWM (p < 0.05). Significantly increased Cho level was also evident in the left PWM (p < 0.05). CONCLUSIONS: Our observations of decreased NAA, NAA/Cr, and NAA/MI, in parallel with increased Cho and MI/Cr might be characteristic of aMCI patients.

[Radiation thermometry based on calibration of spectral responsivity].

Abstract True surface temperatures can be determined by measurements of radiation emitted by the object. The non-spectral parameter in the radiation measurement equation is the function of the relative position between the target and the lens, so calibration of space position is necessary for temperature measurement, when emissivity and temperature are measured simultaneously. In the present paper, the non-spectral parameter was included into the undetermined coefficients of emissivity modeled by finite series, which will not affect the solution of true surface temperature. Therefore, radiation thermometry can be accomplished without calibration of space position and normalization of measurement data. And not the true spectral emissivity but the trend of it can be measured. Two special examples were investigated, respectively. The results indicate that when the effective wavelength of each channel is different, multi-wavelength radiation thermometry equations have the unique solution, while the number of the multiband ones may be zero, one, two or even three.

HSP90-Mediates Liraglutide Preconditioning-Induced Cardioprotection by Inhibiting C5a and NF-κB.

OBJECTIVE: We previously showed that HSP90 is involved in postconditioning cardioprotection by inhibiting complement C5a. Here, we investigated whether HSP90-mediated C5a/NF-κB inhibition is responsible for the cardioprotection conferred by liraglutide. METHODS: Rat hearts underwent a 30 min occlusion of the anterior descending coronary artery, after which reperfusion was performed for 2 h. A total of 100 rats were randomly assigned to the following groups: ischemia/reperfusion (I/R), sham, liraglutide preconditioning (LP, liraglutide, 0.18 mg/kg, intravenously, 12 h before ischemia), HSP90 inhibitor geldanamycin (GA, 1 mg/kg, intraperitoneally, 30 min before ischemia) plus LP, and C5a receptor antagonist PMX53 (1 mg/kg, intravenously, 30 min before ischemia) plus LP. Cardiac injury, C5a/NF-κB activation, and inflammation were investigated. RESULTS: LP significantly attenuated I/R-induced cardiomyocyte apoptosis, infarct size, and secretion of creatine kinase-MB, lactate dehydrogenase and cardiac troponin I. These effects were complemented by decreased C5a levels, nuclear factor (NF)-κB signaling, inflammatory cytokine expression, and increased HSP90 levels. GA, an HSP90 inhibitor, promotes C5a activation, NF-κB signaling, and inflammation and suppresses cardioprotection by LP. By contrast, PMX53, a C5a inhibitor, suppressed C5a activation, NF-κB signaling, and inflammation, and enhanced cardioprotection by LP. CONCLUSION: HSP90 markedly contributes to LP cardioprotection by inhibiting inflammatory responsesand C5a/NF-κB signaling , ultimately attenuating I/R-induced cardiomyocyte apoptosis by suppressing the proapoptotic factor Bax, and inducing the anti-apoptotic factor Bcl2.

Identification of Circular RNA Expression Profiles in White Adipocytes and Their Roles in Adipogenesis.

Obesity and its related metabolic diseases have become great public health threats worldwide. Although accumulated evidence suggests that circRNA is a new type of non-coding RNAs regulating various physiological and pathological processes, little attention has been paid to the expression profiles and functions of circRNAs in white adipose tissue. In this study, 3,771 circRNAs were detected in three stages of white adipogenesis (preadipocyte, differentiating preadipocyte, and mature adipocyte) by RNA-seq. Experimental validation suggested that the RNA-seq results are highly reliable. We found that nearly 10% of genes which expressed linear RNAs in adipocytes could also generate circRNAs. In addition, 40% of them produced multiple circRNA isoforms. We performed correlation analysis and found that a great deal of circRNAs (nearly 50%) and their parental genes were highly correlated in expression levels. A total of 41 differential expression circRNAs (DECs) were detected during adipogenesis and an extremely high ratio of them (80%) were correlated with their parental genes, indicating these circRNAs may potentially play roles in regulating the expression of their parental genes. KEGG enrichment and GO annotation of the parental genes suggesting that the DECs may participate in several adipogenesis-related pathways. Following rigorous selection, we found that many up-regulated circRNAs contain multiple miRNAs binding sites, such as miR17, miR-30c, and miR-130, indicating they may potentially facilitate their regulatory functions by acting as miRNA sponges. These results suggest that plenty of circRNAs are expressed in white adipogenesis and the DECs may serve as new candidates for future adipogenesis regulation.

[Inner-heating acupuncture of lumbar degenerative lesions based on ß-catenin signaling pathway].

OBJECTIVE: By observing the effect of inner-heating acupuncture on the expression of Wnt1, Axin and ß-catenin in the intervertebral disc of rats with lumbar degenerative disease and to explore the regulatory mechanism of inner-heating acupuncture on the apoptosis of annulus fibrosus cells in rats with lumbar degenerative disease. METHODS: Forty SD rats were randomly divided into normal group, model group, inner heating acupuncture group and acupuncture group with 10 rats in each group. Except for normal group, all rats were modeled. Bilateral Da Chang Shu were selected for inner-heating acupuncture and acupuncture treatment. Western-bolt assay was used to detect the expression of Wnt1, Axin and ß-catenin in rat intervertebral discs. RESULTS: Compared with the model group, Wnt1 and ß-catenin expression in annulus fibrosus cells of rats in the inner heating acupuncture group and the acupuncture group were significantly decreased(P<0.05);the expression of Axin in annulus fibrosus of rats in the inner heating acupuncture group was significantly increased(P<0.05). There was no significant difference in the expression of Axin in annulus fibrosus of rats between acupuncture group and model group(P>0.05). CONCLUSION: Inner heating acupuncture can down regulate the expression of Wnt1 and ß-catenin and up regulate the expression of Axin in annulus fibrosus of rats with lumbar degenerative desease. It is suggested that the mechanism may be to regulate the expression of related factors in the ß-catenin signaling pathway, so as to achieve the goal of treating lumbar degenerative diseases.

[Treatment of knee osteoarthritis with six-step manipulation combined with extracorporeal shock wave].

OBJECTIVE: To observe the clinical effect of six-step manipulation combined with extracorporeal shock wave in the treatment of knee osteoarthritis. METHODS: Seventy-six patients with KOA from December 2016 to June 2018 were divided into control group and treatment group, 38 in each group. The patients in the control group were treated with oral medicine combined with extracorporeal shock wave therapy, while the patients in the treatment group were treated with six-step manipulation combined with shock wave therapy. The VAS score, WOMAC score and clinical efficacy of the two groups were compared before treatment, 1 day, 1 month and 6 months after treatment. RESULTS: There was no significant difference in VAS score and WOMAC score between the two groups before treatment(P>0.05). VAS score and WOMAC score in treatment group were significantly lower than those in control group at 1 day, 1 month and 6 months after treatment, and the difference was statistically significant(P<0.05). CONCLUSIONS: Six-step manipulation combined with extracorporeal shock wave therapy can significantly alleviate pain and improve knee function in patients with knee osteoarthritis, and the clinical effect is obvious.

[Relationship between temperature range and wavelength bandwidth for multi band pyrometry].

In the present paper, based on the linearity spectral emissivity model with two parameters in the narrow investigated waveband, we extend tri-wavelength pyrometry to tri-band pyrometry through waveband measurements of radiation temperature. In tri-band pyrometry, in order to realize the non-distortion measurement, considering the effect of the dynamic range and the minimum sensibility of the sensor on the coupling relation of multi-channel signals, the restriction condition of the effective temperature measurement range is discussed. However, under the assumption of the fixed sensor parameters, the measurement bandwidth of the sensor is an important influencing factor to the effective temperature measurement range in applications of tri-band pyrometry. Then for the measured objects with the known radiation characteristics, the variation of the effective temperature measurement range with the bandwidth of the sensor is presented through numerical simulations. So the required condition of bandwidth of the sensor is theoretically determined through the above discussions of the effective temperature measurement range. The analyses in this paper may provide the necessary theoretical guides to the design of the sensor of radiation temperature measurement.

[Analyses of spectral emissivity in radiation temperature measurement].

The complexity of the spectral emissivity of actual surfaces is the key point in the research and applications of radiation temperature measurement, resulting in the difficulty in the achievement of the temperature measurement. In the present paper, based on the discussions of the Taylor expansion, the non-dimension wavelength and the exponent, the authors describe the mathematical expression of the spectral emissivity of actual surfaces, and establish the general spectral emissivity function. Through the fitting of experimental data of the spectral emissivities of different metals at different temperatures, the applicability of the spectral emissivity function is verified which especially becomes the fundamental in the research of primary spectrum pyrometry.

[Determination of chlorophyll a and b using absorption spectrum].

Chlorophyll a and chlorophyll b play a significant role in the plant growth process. Precise determination of its content could provide the scientific basis for the corps growth state, the plant pathology diagnosis and so on, and is the key point of implementing accurate agriculture. The authors transfered the absorption spectrum experiment data of chlorophyll a and chlorophyll b determined by predecessor into a transmission spectrum. Observing the transmission spectrum using human eyes, the color of chlorophyll a and chlorophyll b was obtained. Thus, according to the predecessor's experiment curve of absorption spectrum of chlorophyll a and chlorophyll b, combining the three primary color principles of colorimetry, and choosing a standard light source with spectrum power distribution similar to D65 as the illumination, the authors determined their chromaticity coordinates in the 1931CIE-x, y chromaticity diagram: Chlorophyll a is (0.198 1, 0.334 1), which falls in the cyan color region; Chlorophyll b is (0. 270 4, 0. 566 3), which falls in the yellowish green region. The main point of above processing is: reducing the spectrum curves of chlorophyll a and the chlorophyll b to coordinates on the chromaticity diagram, and the result could offer the essential theoretical support for a new non-contact, long-distance and non-damage technology to determine the pigment content in single leaf or mass.

[Effects of protease inhibitors on the activities of midgut proteases in Callosobruchus chinensis (Linnaeus) larvae.] / è›‹ç™½é ¶æŠ‘åˆ¶å‰‚å¯¹ç»¿è±†è±¡å¹¼è™«ä¸­è‚ è›‹ç™½é ¶æ´»æ€§çš„å½±å“.

To clarify the effects of protease inhibitors on the activities of midgut proteases in Callosobruchus chinensis (L.) larvae, the inhibitory effects of four kinds of protease inhibitors on the activities of midgut proteases of C. chinensis larvae were examined in vitro and in feeding conditions with indoor artificial insect inoculation. The activities of total protease, trypsin-like enzyme and chymotrypsin-like enzyme in the midgut of C. chinensis larvae fed on artificial mung bean that contained different contents of mung bean types in inhibitor (MBTI) were examined. The results showed that those four protease inhibitors had significant inhibitory effects on the activities of total protease, trypsin-like enzyme and chymotrypsin-like enzyme in C. chinensis larvae. The inhibitory effect was more significant when the concentration was higher. Among those inhibitors, the inhibitory effect of 20 µg·mL-1 MBTI on three kinds of enzyme activities was the strongest, with reduction of 62.5%, 41.2% and 38.7%, respectively. Ovomucoid inhibitor (OI) had the lowest inhibitory effect. The activities of three enzymes in the midgut were also inhibited by C. chinensis larvae fed with artificial mung bean containing different inhibitors. The activities of three enzymes increased with the prolongation of the instar after feeding, but they were significantly lower than that in control. The inhibitory effect of MBTI was the strongest. The inhibitory effect on the activities of total protease and trypsin-like enzyme was gradually enhanced with the increases of MBTI contents when C. chinensis larvae were fed with artificial mung bean with different contents MBTI. The inhibitory effect on chymotrypsin-like enzyme activity was not significant. When the content of MBTI was up to 20%, the activity of chymotrypsin-like enzyme was obviously inhibited.

Cytoprotective effects of paeoniflorin are associated with translocator protein 18 kDa.

Paeoniflorin (PF) is one of the important active components in peony that are known to produce the neuroprotective effects. However, the involved cytoprotective factors on brain astrocytes are remain unclear. Translocator protein 18 kDa (TSPO) and its downstream neurosteroids biosynthesis play a significant role in cytoprotection. Based on these, the role of TSPO and neurosteroids biosynthesis in the cytoprotective effects of PF is evaluated. The astrocyte cells were cultured and AC-5216 (TSPO ligand) was selected as the positive control drug. The cytoprotective effects of PF and the levels of neurosteroids were quantified by water-soluble tetrazolium assay and enzyme linked immunosorbent assay, respectively. The cytoprotective activities of PF were relevant to neurosteroids (e.g. progsterone and allopregnanolone) biosynthesis, while these effects were totally blocked by PK11195, trilostane and finasteride, respectively. In summary, the cytoprotective effects of PF maybe mediated by TSPO and neurosteroids biosynthesis. The findings may provide the new insights into the cytoprotective effects of PF.

[The temperature field partition for primary spectrum pyrometry].

In the applications of primary spectrum pyrometry to the detection of temperature, through the analysis of the coupled multi-channel signals, the authors investigated the necessary condition under which all temperatures can be measured simultaneously and effectively. For the case not satisfying the above condition, the authors put forward the concept of temperature field partition. And the process of the temperature field partition is detailedly described, and the simulation results are given. Ths study is significative for the applications of primary spectrum pyrometry.

[Correlativity analysis based on radiation spectrum of correlated color temperature and thermodynamic temperature of a radiating source].

Correlated color temperature, which describes the chromaticity characteristics of a radiating source, is different from its thermodynamic temperature derived from primary spectrum pyrometry. However, establishing their mathematical relationship is feasible. Therefore, the authors theoretically analyzed the variation rule of the correlativity difference between the correlated color temperature of the source and its thermodynamic temperature with the emissivity parameter. And the authors gave the corresponding numerical simulation results. The above theoretical and numerical discussions will make it possible that a colorimeter used to measure the correlated color temperature serves as a pyrometer to realize the measurement of the thermodynamic temperature.

[Optimization analysis based on wavelength bandwidth for multi-band pyrometry].

The present paper establishes the optimization criteria for achieving the optimum measurements in three-band pyrometry under the assumption of linear emissivity model and the sensor design with Gaussian distribution. By varying the FWHM of Gaussian distribution, the optimization analysis is investigated with the choice of the wavelength bandwidth in three-band pyrometry. For specific cases, the simulation results present the optimum bandwidth distribution. Therefore, the discussions in this paper will provide significant theoretical instructions for the design of radiation pyrometer.

[Theoretical analysis of wavelength choice in tri-wavelength method of temperature measurement].

In this paper, a non-dimensional emissivity model with universality is established. For the tri-wavelength method of temperature measurement, based on the non-dimensional emissivity, the applicable measurement condition and theoretical analysis of wavelength choice are mainly introduced. In the discussion of theoretical analysis of wavelength choice, by optimizing the analysis of measurement method and the concept of isothermal line induced by the measurement coordinates, two kinds of ideal choice rules of measurement wavelength are put forward, which will be necessary to the technology application of this tri-wavelength method. Meanwhile the optimizing idea is also applicable to multi-wavelength method of temperature measurement.