Curcumin alleviates myocardial inflammation, apoptosis, and oxidative stress induced by acute pulmonary embolism by regulating microRNA-145-5P/insulin receptor substrate 1 axis.

The treatment of patients with acute pulmonary embolism (APE) is extremely challenging due to the complex clinical presentation and prognosis of APE related to the patient's hemodynamic status and insufficient arterial blood flow and right ventricular overload. Protective efficacy against cardiovascular diseases of curcumin, a common natural polyphenolic compound, which has antithrombotic properties and reduces platelet accumulation in the circulation by inhibiting thromboxane synthesis has been demonstrated. However, the direct effect of curcumin on APE has rarely been studied. Therefore, the present study aimed to investigate the therapeutic potential of curcumin in APE and associated myocardial injury to provide new insights into curcumin as a promising competitive new target for the treatment of APE. A suspension of 12 mg/kg microspheres was injected intravenously into rats. An APE rat model was built. Before modeling, intragastric 100 mg/kg curcumin was given, and/or lentiviral plasmid vector targeting microRNA-145-5p or insulin receptor substrate 1 (IRS1) was injected. Pulmonary artery pressure was measured to assess right ventricular systolic pressure (RVSP). Hematoxylin and eosin (H&E) staining was performed on liver tissues and myocardial tissues of APE rats. TUNEL (terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling) staining and immunohistochemical (IHC) staining were conducted to measure apoptosis and CyPA-CD147 expression in the myocardium, respectively. Inflammatory indices interleukin-1beta (IL-1ß), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) were measured by ELISA in cardiac tissues. RT-qPCR and Western blot were performed to determine the expression levels of related genes. In addition, by dual luciferase reporter assay and RIP assay, the relationship between microRNA-145-5p and insulin receptor substrate 1 (IRS1) was confirmed. In results: curcumin improved APE-induced myocardial injury, reduced myocardial tissue edema, and thrombus volume. It attenuated APE-induced myocardial inflammation and apoptosis, as well as reduced lung injury and pulmonary artery pressure. Curcumin promoted microRNA-145-5p expression in APE rat myocardium. MicroRNA-145-5p overexpression protected against APE-induced myocardial injury, and microRNA-145-5p silencing abolished the beneficial effects of curcumin in APE-induced myocardial injury. IRS1 was targeted by microRNA-145-5p. IRS1 silencing attenuated APE-induced myocardial injury, and enhanced therapeutic effect of curcumin on myocardial injury in APE rats. In conclusion, curcumin alleviates myocardial inflammation, apoptosis, and oxidative stress induced by APE by regulating microRNA-145-5p/IRS1 axis.

The expression of annexin-A1 in esophageal squamous cell carcinoma and its association with the biological behavior of the primary human esophageal squamous carcinoma cell line.

This study aimed to observe the differential expression of Annexin-A1 in esophageal squamous cell carcinoma (ESCC) and explored the effect of small interfering ribonucleic acid (RNAi)-Annexin-A1 on the biological behavior of CE81T-0 cells. An immunohistochemical approach was used to detect the expression of Annexin-A1 in 86 pairs of ESCC samples. Quantitative reverse transcription polymerase chain reaction was used to detect the expression of Annexin-A1 in CE81T-0 and CE81T-4 cells, and the expression of Annexin-A1 in CE81T-0 cells was knocked out by RNAi. A methyl-thiazolyl-tetrazolium assay was used to observe the effect of Annexin-A1 on cell proliferation, and flow cytometry was conducted to analyze its effect on cell cycles and apoptosis. A scratch assay and a Transwell chamber were used to detect changes in cell migration and invasion. From the results, compared with the Annexin-A1 expression rate of 59.3% in para-carcinoma tissues, the expression of Annexin-A1 in cancer was reduced to only 32.6% in ESCC cells. Annexin-A1 was strongly expressed in highly differentiated ESCC cells without lymphatic metastasis and highly expressed in the CE81T-0 cell group with low metastasis. Annexin-A1 gene silencing promoted cell proliferation and inhibited apoptosis, blocked cells in the S-phase, and increased cell migration, leading to an increase in the number of invaded cells. Above all, Annexin-A1 could reflect the differentiation degree and lymph node metastasis of ESCC cells to some extent and was involved in the invasion, metastasis, proliferation, and other biological behaviors of ESCC cells, indicating an experimental basis for Annexin-A1 as a molecular marker in the early diagnosis of ESCC and the prediction of cell metastasis, invasion, and differentiation degree.

[Association between maternal plasma one-carbon biomarkers during pregnancy and fetal growth in twin pregnancies].

Objective: To characterize the relationship between the levels of plasma methyl donor and related metabolites (including choline, betaine, methionine, dimethylglycine and homocysteine) and fetal growth in twin pregnancies. Methods: A hospital-based cohort study was used to collect clinical data of 92 pregnant women with twin pregnancies and their fetuses who were admitted to Peking University Third Hospital from March 2017 to January 2018. Fasting blood was collected from the pregnant women with twin pregnancies (median gestational age: 18.9 weeks). The levels of methyl donors and related metabolites in plasma were quantitatively analyzed by high-performance liquid chromatography combined with mass spectrometry. The generalized estimation equation was used to analyze the relationship between maternal plasma methyl donors and related metabolites levels and neonatal outcomes of twins, and the generalized additive mixed model was used to analyze the relationship between maternal plasma methyl donors and related metabolites levels and fetal growth ultrasound indicators. Results: (1) General clinical data: of the 92 women with twin pregnancies, 66 cases (72%) were dichorionic diamniotic (DCDA) twin pregnancies, and 26 cases (28%) were monochorionic diamniotic (MCDA) twin pregnancies. The comparison of the levels of five plasma methyl donors and related metabolites in twin pregnancies with different basic characteristics showed that the median levels of plasma choline and betaine in pregnant women ≥35 years old were higher than those in pregnant women <35 years old, and the differences were statistically significant (all P<0.05). (2) Correlation between plasma methyl donor and related metabolites levels and neonatal growth indicators: after adjusting for confounding factors, plasma homocysteine level in pregnant women with twins was significantly negatively correlated with neonatal birth weight (ß=-47.9, 95%CI:-94.3- -1.6; P=0.043). Elevated methionine level was significantly associated with decreased risks of small for gestational age infants (SGA; OR=0.5, 95%CI: 0.3-0.9; P=0.021) and low birth weight infants (OR=0.6, 95%CI: 0.4-0.9; P=0.020). Increased homocysteine level was associated with increased risks of SGA (OR=1.5, 95%CI: 1.0-2.2; P=0.029) and inconsistent growth in twin fetuses (OR=1.9, 95%CI: 1.0-3.7; P=0.049). (3) Correlation between the levels of plasma methyl donors and related metabolites and intrauterine growth indicators of twins pregnancies: for every 1 standard deviation increase in plasma choline level in pregnant women with twin pregnancies, fetal head circumference, abdominal circumference, femoral length and estimated fetal weight in the second trimester increased by 1.9 mm, 2.6 mm, 0.5 mm and 20.1 g, respectively, and biparietal diameter, abdominal circumference and estimated fetal weight increased by 0.7 mm, 3.0 mm and 38.4 g in the third trimester, respectively, and the differences were statistically significant (all P<0.05). (4) Relationship between plasma methyl donor and related metabolites levels in pregnant women with different chorionicity and neonatal birth weight and length: the negative correlation between plasma homocysteine level and neonatal birth weight was mainly found in DCDA twin pregnancy (ß=-65.9, 95%CI:-110.6- -21.1; P=0.004). The levels of choline, betaine and dimethylglycine in plasma of MCDA twin pregnancy were significantly correlated with the birth weight and length of newborns (all P<0.05). Conclusion: Homocysteine level is associated with low birth weight in twins, methionine is associated with decreased risk of SGA, and choline is associated with fetal growth in the second and third trimesters of pregnancy.

[Effect of maternal exposure to lipopolysaccharide during pregnancy on allergic asthma in offspring in mice].

Objective: To investigate the effect of maternal exposure to lipopolysaccharide during pregnancy on allergic asthma in offspring in mice. Methods: Animal experimental research was carried out from June 2019 to June 2021.Pregnant C57BL/6J mice were randomly divided into 2 groups by intraperitoneal injection with 7 µg/kg lipopolysaccharide (LPS) or phosphate buffered saline (PBS) at day 15.5 of gestation. After birth, 6 offspring were randomly chosen from each group at the age of 4 weeks, and stimulated with house dust mites (HDM) or PBS, further divided into 4 groups, such as LPS+PBS group, LPS+HDM group, PBS+PBS group, PBS+HDM group, with 3 mice in each group. The cough and wheezing were observed, the histological changes in lung tissue were examined after HE staining, and the expression of inflammatory factors including interleukin (IL)-4, IL-6, IL-17A, IL-23, interferon (IFN)-α and IFN-ß in the lung tissue were detected by high-throughput liquid protein chip detection. T test or rank sum test was used for the comparison among these groups. Results: The asthma-like airway inflammation was more obvious in PBS+HDM group after stimulated by HDM than that in PBS+PBS group, nevertheless, this manifestation in LPS+HDM group was milder than that in PBS+HDM group. HE staining showed that inflammatory cell aggregation in the lung tissue in PBS+HDM group was significantly higher than that in PBS+PBS group (4.0 (3.5, 4.0) vs. 0 (0, 0.5), Z=2.02, P=0.043), while it was much lower in LPS+HDM group compared to PBS+HDM group (1.0 (0.5, 1.5) vs. 4.0 (3.5, 4.0), Z=1.99, P=0.046). High-throughput liquid protein chip detection of lung tissue showed that IL-6, IL-23 and IFN-ß levels were significantly higher in PBS+HDM group when compared to those in PBS+PBS group ((114±3) vs. (94±4) ng/L, (210±4) vs. (173±7) ng/L, (113±2) vs. (94±4) ng/L, t=4.37, 4.84, 3.96, all P<0.05), while the levels of IL-6, IL-23, IFN-α, IFN-ß in LPS+HDM group were significantly lower than those in PBS+HDM group ((87±5) vs. (114±3) ng/L, (171±7) vs. (210±4) ng/L, (16.1±0.6) vs. (20.9±0.3) ng/L, (95±1) vs. (113±2) ng/L, t=5.07, 5.07, 7.28, 7.47, all P<0.05). Conclusions: Prenatal low dose LPS exposure can reduce offspring's airway inflammatory reactions and prevent the development of allergic disease. Maternal infection during pregnancy may affect the occurrence and development of allergic asthma in offspring.

[Immune checkpoint inhibitors in the treatment of colorectal cancer: a review of clinical trials].

Colorectal cancer is the third most common cancer in the world. The treatments include surgery, chemotherapy, radiotherapy and targeted therapy. The guidelines of many tumor types have been rewritten with the advent of immune checkpoint inhibitors. There are significant differences in the efficacy of immune checkpoint inhibitors in colorectal cancer according to microsatellite status. Microsatellite instability-high (MSI-H) colorectal cancer has made a breakthrough in immunotherapy, whether in the late-line, first-line, adjuvant or neoadjuvant therapy. The success of KEYNOTE-177 study has changed the guidelines with pembrolizumab becoming a standard treatment in the first-line treatment of MSI-H advanced colorectal cancer. The NICHE study, which used immunotherapy as neoadjuvant treatment of colorectal cancer, has made exciting achievements in MSI-H colorectal cancer. For microsatellite stability (MSS) colorectal cancer, many studies are ongoing, and immunotherapy is still unable to challenge the status of traditional treatment. In this paper, we review the clinical trials related to immune checkpoint inhibitors of colorectal cancer, expecting to provide references for the development of colorectal cancer immunotherapy.

[Characteristics and outcomes of primary angiosarcoma].

Objective: The study was designed to analyze the clinicopanthologic characteristics, treatments and outcomes of a series of patients with primary angiosarcoma. Methods: The clinical, surgical and pathological data and treatment of 68 patients with pathologically confirmed angiosarcoma admitted to Peking Union Medical College Hospital from January 1990 to June 2017 was retrospectively analyzed. Kaplan-Meier method and Log rank test were used for univariate survival analysis and Cox regression model was used for multivariate survival analysis. Results: A total of 68 patients were enrolled, 38 were male, 30 were female. The median age at diagnosis was 50.5 years. The time from symptom onset to diagnosis was (7.5±7.5) months. The primary sites included face and scalp, breast, chest wall, lung, heart, liver, spleen, extremities, bones and so on. At diagnosis, the mean size of tumors were (7.4±7.3) cm, 28 patients (41.2%) had localized disease (stage Ⅰ+ Ⅱ) and 40 patients had metastatic disease (stage Ⅲ+ Ⅳ). There were 37 patients treated with surgery alone, three receiving radiotherapy alone, five receiving chemotherapy alone and sixteen receiving comprehensive treatment with 5 underwent surgery plus radiotherapy, three treated by surgery plus chemotherapy, four had surgery plus interventional therapy, two had chemoradiotherapy, one had radiotherapy and interventional therapy and 1 had surgery plus chemoradiotherapy and targeted therapy. Five patients received only palliative treatment, and 2 patients lost follow-up after diagnosed. Fifty patients were followed up with a median overall survival time of 8.5 months. The median survival time of patients with metastatic angiosarcoma was 6.6 months, significantly shorter than that of patients with localized disease (15.0 months, P=0.020). The median survival time of patients with cardiac angiosarcoma was 3.0 months, significantly shorter than that of patients with angiosarcoma at other sites (11.5 months, P=0.010). The median survival time of patients receiving comprehensive treatment was 31.0 months, significantly longer than that of patients without comprehensive treatment (5.6 months, P=0.007). Multivariate analysis showed that staging, heart occurrence and comprehensive treatment were independent factors for the prognosis of primary angiosarcoma (all P<0.05). Conclusions: Angiosarcoma is a rare malignancy, and patients with metastatic disease or cardiac occurence have poor prognosis. Comprehensive treatment can improve the prognosis of patients with angiosarcoma.

[Advances in clinical research on rtA181 mutation in hepatitis B virus].

Nowadays, nucleos(t)ide analogues (NAs) are important drugs for the treatment of chronic hepatitis B and can suppress the virus through inhibiting the activity of hepatitis B virus (HBV) polymerase. However, rtA181 mutation in HBV can reduce the sensitivity of HBV to various NAs, which brings new challenges to antiviral therapy. This article briefly introduces the research advances in the clinical detection rate of rtA181 mutation and its influence on therapeutic effect and prognosis.

A mixture approach to the acoustic properties of a macroscopically inhomogeneous porous aluminum in the equivalent fluid approximation.

The acoustic properties of an air-saturated macroscopically inhomogeneous aluminum foam in the equivalent fluid approximation are studied. A reference sample built by forcing a highly compressible melamine foam with conical shape inside a constant diameter rigid tube is studied first. In this process, a radial compression varying with depth is applied. With the help of an assumption on the compressed pore geometry, properties of the reference sample can be modelled everywhere in the thickness and it is possible to use the classical transfer matrix method as theoretical reference. In the mixture approach, the material is viewed as a mixture of two known materials placed in a patchwork configuration and with proportions of each varying with depth. The properties are derived from the use of a mixing law. For the reference sample, the classical transfer matrix method is used to validate the experimental results. These results are used to validate the mixture approach. The mixture approach is then used to characterize a porous aluminium for which only the properties of the external faces are known. A porosity profile is needed and is obtained from the simulated annealing optimization process.

Study on CH(4) and N(2)O emissions from water-saving irrigation in Phaeozem paddy fields in cold areas.

Increasing greenhouse gas emissions and water shortage are two main problems associated with cultivation of rice. Soil moisture control is not only a core technology in water-saving irrigation, but also a decisive factor of greenhouse gas emissions. The CH(4) and N(2)0 emission fluxes from intermittent irrigation and flooding irrigation in Phaeozem paddy fields in cold area were measured in-situ to provide a theoretical basis for studying the regulation of CH(4) and N(2)O emissions and comprehensive assessing the effect of intermittent irrigation on the environment and control of greenhouse gas emissions. During the rice growing period, CH(4) emissions peaked at the tillering stage, whilst N(2)0 emissions peaked twice at the tillering and milky ripening stages. The accumulated emission of N(2)O from the implementation of flooding irrigation in paddy fields was 6.46 gm(-2), whilst that from intermittent irrigation was 5.47 gm(-2). The accumulated emission of N(2)0 from the implementation of flooding irrigation in paddy fields was 36.88 mgm(-2), whilst that from intermittent irrigation was 68.47 mgm(-2). The global warming potential of CH(4) and N(2)0 was 1362.7lkgCO(2)ha(-1) from intermittent irrigation in paddy fields, a value 108.12 kgCO(2)ha(-1) lower than that from flooding irrigation. Intermittent irrigation can thus be used to effectively decrease and control the combined greenhouse effect of CH4 and N20 emissions from rice paddy fields.

Note: Dynamic strain field mapping with synchrotron X-ray digital image correlation.

We present a dynamic strain field mapping method based on synchrotron X-ray digital image correlation (XDIC). Synchrotron X-ray sources are advantageous for imaging with exceptional spatial and temporal resolutions, and X-ray speckles can be produced either from surface roughness or internal inhomogeneities. Combining speckled X-ray imaging with DIC allows one to map strain fields with high resolutions. Based on experiments on void growth in Al and deformation of a granular material during Kolsky bar/gas gun loading at the Advanced Photon Source beamline 32ID, we demonstrate the feasibility of dynamic XDIC. XDIC is particularly useful for dynamic, in-volume, measurements on opaque materials under high strain-rate, large, deformation.

Genetic evidence for panmixia of Japanese eel (Anguilla japonica) populations in China.

The Japanese eel population has dramatically declined since the 1970s. In order to conserve this species, the background genetic structure affecting these populations should be well documented. Previous genetic studies of this species have produced seemingly conflicting results, ranging from no detectable heterogeneity to small, but statistically significant variance. This study investigates the population structure of Japanese glass eels collected from 10 localities in China in 2009 using a mitochondrial DNA (mtDNA) control region and 19 polymorphic microsatellite loci. Results revealed evidence of low genetic differentiation using both mtDNA (FST = 0.001, P = 0.291) and microsatellite data (FST = 0.003, P = 0.008). Pairwise F-statistic values generated from mtDNA and microsatellite DNA were similar, showing little evidence of significant genetic differentiation. The minimum spanning haplotype network constructed using mtDNA control regions produced no clear phylogeographic structure. The Mantel test revealed no significant correlation with distances for both mtDNA and microsatellite DNA. Therefore, our results suggest a panmictic population of Japanese eels in China, which should be conserved as a single management unit.

Simulation study on the trembling shear behavior of eletrorheological fluid.

The trembling shear behavior of electrorheological (ER) fluids has been investigated by using a computer simulation method, and a shear-slide boundary model is proposed to understand this phenomenon. A thiourea-doped Ba-Ti-O ER fluid which shows a trembling shear behavior was first prepared and then systematically studied by both theoretical and experimental methods. The shear curves of ER fluids in the dynamic state were simulated with shear rates from 0.1 to 1000 s(-1) under different electric fields. The simulation results of the flow curves match the experimental results very well. The trembling shear curves are divided into four regions and each region can be explained by the proposed model.

Boundary effect in electrorheological fluids.

The effect of the boundary friction coefficient on the rheological properties of the electrorheological (ER) fluids in quasistatic and dynamic states is investigated by computer simulation. The relation between the shear stress and the boundary friction coefficient in quasistatic and dynamic states is discussed qualitatively and quantitatively, and the trend matches the previously reported experimental results well. The flow curves of ER fluids, under different friction coefficients, are calculated, and it is found that the friction coefficient affects the flow curves. In two dimensions, the transitions in structure corresponding to the shear stress variations are presented to understand the mechanism of ER fluids.

Redescription of Myxobolus pyramidis Chen, 1958(Myxosporea: Bivalvulida).

Redescription of Myxobolus pyramidis Chen, 1958, from gill lamellae of allogynogenetic gibel carp, Carassius auratus gibelio (Bloch), is presented in this paper to complete Chen's description. The diagnostic characters of the myxosporidia are: ovoid round, greyish-white polysporous plasmodia, averaging (159+/-21)x(72+/-6.5) mum in size; spore pyriform in front view with smooth surface and symmetrical valves, convex-shaped in sutural view with straight and thick sutural line, averaging (10.5+/-1.1)x(10.3+/-0.9)x(6.1+/-0.2) mum in size; two equal pyriform polar capsules averaging (5.5+/-0.7)x(3.5+/-0.2) mum in size with distinct intercapsular process and polar filament wounded in five to six coils. The histological effects of the pathogen were observed by light microscopy, and the parasite-host relationship was discussed.

A combined phage display ScFv library against Myxobolus rotundus infecting crucian carp, Carassius auratus auratus (L.), in China.

Immunological methods have been developed for the diagnosis of Myxobolus rotundus but their use has been limited for the prevention and therapy of this serious parasitic pathogen. Phage display antibody libraries are a powerful technique for the development of antibodies to molecules of interest and have advantages over traditional hybridroma approaches. In the present study, four antigen fractions related to M. rotundus were prepared and a combined phage display single-chain antibody fragments (ScFv) library was constructed against this parasite. Preliminary analysis indicated that a combined antibody library of about 2.08 x 10(5) individual clones and high diversity was generated. After four rounds of screening (bio-panning) against soluble spore protein prepared from lysed, intact, mature M. rotundus spores, a strain monoclonal phage display ScFv, termed pCAN-6H9, with better affinity, was isolated. The pCAN-6H9 gene fragment was sequenced and analysed. The specificity of pCAN-6H9 was further demonstrated by dot-blot. In competition enzyme-linked immunosorbent assay, both the original and enriched phage-displayed ScFv repertoire showed significant inhibition of mouse anti-M. rotundus serum binding to coated antigen, while the inhibition rate of monoclonal pCAN-6H9 phage particles was only 11.83%.

Regulation of apoptosis by a Caenorhabditis elegans BNIP3 homolog.

We have identified a C. elegans protein, ceBNIP3, homologous to the human BCL-2/EIB-19K interacting BCL-2 family pro-apoptotic protein BNIP3. In transiently transfected mammalian cells, ceBNIP3 complexes with CED-9, the worm homolog of BCL-2. CeBNIP3 also efficiently heterodimerizes with the cell death protease proCED-3 by direct binding via the prodomain. Transfection of ceBNIP3 and CED-3 results in enhanced proteolytic processing of the CED-3 zymogen and in cooperative induction of apoptosis. Coexpression of CED-9 suppresses the cooperative cell death induced by ceBNIP3 and CED-3. In cells coexpressing CED-9, ceBNIP3 and CED-3, all three proteins exist as a ternary complex suggesting that CED-9 may suppress cooperative apoptosis induced by CED-3 and ceBNIP3 by simultaneous complex formation with CED-3 and ceBNIP3. Our results suggest that ceBNIP3 may be a novel component of the C. elegans apoptosis paradigm and may initiate apoptosis by recruiting CED-3 to mitochondria and other cytoplasmic membranes.

[Effect of hematoporphyrin derivative (HPD) plus light on DNA repair synthesis and enhancement of HPD photosensitization by vitamin C in mouse hepatoma].

There are only a few reports in the literature on photodynamic effects of HPD on gene expression and the repair of DNA damage. Previously, we suggested that nuclear transcription activity was markedly suppressed by HPD plus light. In this study, we investigated the photodynamic effect or DNA repair synthesis as measured by unscheduled DNA synthesis (UDS) in hepatoma cells. The results indicated that DNA repair capacity was greatly inhibited by HPD plus light. When hepatoma cells were pretreated with HPD of different concentrations and then exposed to the same light dose, significant inhibitions of UDS over control were seen and appeared in a dose-dependent fashion. In addition, while hepatoma cells following the exposure to HPD of the same concentration were irradiated with different time, the UDS was markedly decreased as the duration of irradiation was prolonged. However, no changes were observed when either HPD or light was used alone. The present study also included an experiment to determine whether HPD combined with vitamin C gives an enhanced photosensitization. It was found that vitamin C significantly potentiated the suppressing effect on DNA repair synthesis.