Mechanisms of myocardial ischemic injury repair by bone marrow mesenchymal stem cell-derived miR-183-5P targeting FOXO1.

The homing rate of transplanted mesenchymal stem cells (BMSCs) after acute myocardial infarction (AMI) is generally low, with only 0%-6% of the number of transplanted stem cells distributed to the heart; therefore, this study will investigate the therapeutic effects and mechanisms of miR-183-5p-modified BMSCs cells on myocardial ischemia and hypoxia caused by AMI. In this experiment, After first establishing the BMSCs ischemic-hypoxic injury model, the rats were divided into healthy group, model group, BMSCs group and BMSCs+ miR-183-5P group, where the healthy group was taken to normal culture, the model group caused myocardial ischemic-hypoxic damage, the BMSCs group underwent BMSCs stem cell transplantation on the basis of the model group, and the BMSCs+ miR-183-5P group was group was cultured with BMSCs-derived miR-183-5P on the basis of the model group. Myocardial tissue sections of rats in each group were taken for HE staining and histopathological changes were observed by light microscopy. The proliferation, apoptosis and migration ability of the cells were detected by CCK-8 method, flow cytometry and Transwell transfer method. The target gene of miR-183-5P was predicted using bioinformatics software, and the binding of miR-183-5P to FOXO1 was investigated. The expression of FOXO1 was analysed using qRT-PCR and protein blotting techniques. The qRT-PCR results showed that the expression of miR-183-5P was higher in BMSCs of the BMSCs group and BMSCs+ miR-183-5P group compared with the model group, and the expression was highest in the BMSCs+ miR-183-5P group (P<0.05). The value-added ability and the migration capacity of BMSCs in the BMSCs group and BMSCs+ miR-183-5P group were increased compared with the model group, and the BMSCs+ miR-183-5P group BMSCs had the highest proliferation capacity and the migration capacity(P<0.05). In contrast, the apoptotic capacity of BMSCs was significantly reduced in the BMSCs group and BMSCs+ miR-183-5P group compared with the model group, and the apoptotic capacity of BMSCs was lowest in the BMSCs+ miR-183-5P group (P<0.05). The bioinformatics software RegRNA 2. 0 was used to predict that the specific target gene that may be regulated by miR-183-5P is FOXO1 and confirmed that miR-183-5P does indeed have a targeting relationship with the FOXO1 pathway. After upregulation of miR-183-5P expression, the expression of FOXO1 mRNA was higher in BMSCs of the BMSCs group and BMSCs+ miR-183-5P group compared with the model group, and the expression was highest in the BMSCs+ miR-183-5P group (P<0.05). The Western blotting showed that the expression of FOXO1 mRNA was higher in BMSCs of the BMSCs group and BMSCs+ miR-183-5P group compared with the model group, especially the expression was highest in the BMSCs+ miR-183-5P group (P<0.05). In conclusion, BMSCs-derived miR-183-5P can target and regulate FOXO1 to increase the proliferation and migration of BMSCs and reduce their apoptosis, and can also reduce myocardial tissue edema and inflammatory response by increasing the expression of FOXO1 mRNA, which can increase the survival rate of BMSCs and provide a clinical basis for BMSCs transplantation.

Earthquake-induced soil landslides: volume estimates and uncertainties with the existing scaling exponents.

Quantifying landslide volumes in earthquake affected areas is critical to understand the orogenic processes and their surface effects at different spatio-temporal scales. Here, we build an accurate scaling relationship to estimate the volume of shallow soil landslides based on 1 m pre- and post-event LiDAR elevation models. On compiling an inventory of 1719 landslides for 2018 Mw 6.6 Hokkaido-Iburi earthquake epicentral region, we find that the volume of soil landslides can be estimated by γ = 1.15. The total volume of eroded debris from Hokkaido-Iburi catchments based on this new scaling relationship is estimated as 64-72 million m3. Based on the GNSS data approximation, we noticed that the co-seismic uplift volume is smaller than the eroded volume, suggesting that frequent large earthquakes (and rainfall extremes) may be counterbalancing the topographic uplift through erosion by landslides, especially in humid landscapes such as Japan, where soil properties are rather weak.

Potential molecular mechanism of the Xiexin capsule in the intervention of dyslipidemia based on bioinformatics and molecular docking / Posible mecanismo molecular de la cápsula Xiexin en la intervención de la dislipidemia basada en la bioinformática y el acoplamiento molecular

Objective: bioinformatic methods and molecular docking technology were used to predict the active components, targets, and related biological pathways of the Xiexin capsule in the intervention for dyslipidemia, exploring its mechanism. Methods: the active components and targets of the Xiexin capsule were screened by the TCMSP (Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform )database. Genecards (The Human Gene Database), OMIM (Online Mendelian Inheritance in Man), PharmGkb (Pharmacogenomics Knowledge Base database), TTD (Therapeutic Target Database), and Drugbank platforms were used to search the disease targets of dyslipidemia. The Cytoscape 3.8.0 software was used to construct the 'component-target' network diagram, and the STRING (functional protein association networks) platform was used to analyze protein-protein interaction (PPI). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomics (KEGG) enrichment analyses were performed by R language data packets to predict the mechanism of action. The AutoDockVina and PyMol software were used to dock the key active components in the Xiexin capsule and the core proteins in PPI. Results: a total of 66 effective components were screened, involving 114 targets; 87 key active compounds were screened from the 'drug-component-target' diagram. The PPI network mainly involved core proteins such as PTGS2 (prostaglandin-endoperoxide synthase 2), PTGS1 (prostaglandin-endoperoxide synthase 1), and HSP90AA1 (heat shock protein 90 alpha family class A member 1). GO and KEGG enrichment analysis results of common targets mainly involved hormone-mediated signaling pathway, steroid hormone response, lipid transport and metabolism, regulation of cholesterol storage, cyclooxygenase pathway, and other biological pathways, as well asMM PPAR (peroxisome proliferators-activated receptor) signaling pathway, IL-17 (interleukin 17) signaling pathway (AU)

Objetivo: se utilizaron métodos bioinformáticos y técnicas de acoplamiento molecular para predecir los componentes efectivos, los objetivos y las vías biológicas relacionadas de la cápsula Xiexin en la intervención de la dislipidemia y explorar su mecanismo. Métodos: los componentes activos y los objetivos de la cápsula Xiexin fueron seleccionados por la base de datos TCMSP. Se utilizaron las plataformas Genecards, OMIM, PharmGkb, TTD (Therapeutic Target Database) y Drugbank para buscar las dianas de la enfermedad en la dislipidemia. El diagrama reticular “componente-diana” fue construido por el software Cytoscape 3.7.0, y la interacción proteína-proteína (PPI) fue analizada por la plataforma STRING. Los análisis de enriquecimiento de Gene Ontology (GO) y Kyoto Encyclopedia of Genes and Genomics (KEGG) se realizaron mediante paquetes de datos en lenguaje R para predecir el mecanismo de acción. El software AutoDockVina y PyMol se utilizó para unir los componentes activos clave de la cápsula Xiexin y las proteínas clave de la PPI. Resultados: se seleccionaron 65 componentes activos y 114 dianas. Veintitrés compuestos activos clave fueron seleccionados a partir de la tabla “componentes farmacéuticos-dianas”. Las redes PPI incluyen principalmente proteínas básicas como PTGS2, PTGS1 y HSP90AA1. Los resultados del análisis de enriquecimiento de GO y KEGG en los objetivos comunes se refieren principalmente a la vía de señalización mediada por esteroides, la respuesta hormonal esteroidea, el transporte y metabolismo lipídicos, la regulación del almacenamiento de colesterol, la vía de la ciclooxigenasa y otras vías biológicas, así como la vía de señalización de PPAR, la vía de señalización de IL-17, la vía de señalización de PI3K-Akt (AU)

Initial Preclinical Evaluation of 18F-Fluorodeoxysorbitol PET as a Novel Functional Renal Imaging Agent.

Accurate assessment of kidney function plays an essential role for optimal clinical decision making in a variety of diseases. The major intrinsic advantages of PET are superior spatial and temporal resolutions for quantitative tomographic renal imaging. 2-deoxy-2-18F-fluorodeoxysorbitol (18F-FDS) is an analog of sorbitol that is reported to be freely filtered at the renal glomerulus without reabsorption at the tubule. Furthermore, it can be synthesized via simple reduction of widely available 18F-FDG. We tested the feasibility of 18F-FDS renal PET imaging in rats. METHODS: The systemic and renal distribution of 18F-FDS were determined by dynamic 35-min PET imaging (15 frames × 8 s, 26 frames × 30 s, 20 frames × 60 s) with a dedicated small-animal PET system and postmortem tissue counting in healthy rats. Distribution of coinjected 99mTc-diethylenetriaminepentaacetic acid (DTPA) was also estimated as a reference. Plasma binding and in vivo stability of 18F-FDS were determined. RESULTS: In vivo PET imaging visualized rapid excretion of the administrated 18F-FDS from both kidneys, with minimal tracer accumulation in other organs. Initial cortical tracer uptake followed by visualization of the collecting system could be observed with high contrast. Split-function renography curves were successfully obtained in healthy rats (the time of maximal concentration [Tmax] right [R] = 2.8 ± 1.2 min, Tmax left [L] = 2.9 ± 1.5 min, the time of half maximal concentration [T1/2max] R = 8.8 ± 3.7 min, T1/2max L = 11.1 ± 4.9 min). Postmortem tissue counting of 18F-FDS confirmed the high kidney extraction (kidney activities at 10, 30, and 60 min after tracer injection [percentage injected dose per gram]: 1.8 ± 0.7, 1.2 ± 0.1, and 0.5 ± 0.2, respectively) in a degree comparable to 99mTc-DTPA (2.5 ± 1.0, 1.5 ± 0.2, and 0.8 ± 0.3, respectively). Plasma protein binding of 18F-FDS was low (<0.1%), and metabolic transformation was not detected in serum and urine. CONCLUSION: In rat experiments, 18F-FDS demonstrated high kidney extraction and excretion, low plasma protein binding, and high metabolic stability as preferable properties for renal imaging. These preliminary results warrant further confirmatory studies in large animal models and clinical studies as a novel functional renal imaging agent, given the advantages of PET technology and broad tracer availability.

Structural development of wheat nutrient transfer tissues and their relationships with filial tissues development.

Nutrients from spikelet phloem are commonly delivered to endosperm via caryopsis nutrient transfer tissues (NTTs). Elucidation of NTTs development is paramount to developing an understanding of the control of assimilate partitioning. Little information was available on the structural development of the entire NTTs and their functions, particularly those involved in the relationship between development of NTTs and growth of filial tissues including endosperm and embryo. In this study, wheat caryopses at different development stages were collected for observation of the NTTs by light microscopy, stereoscopic microscopy, and scanning electron microscopy. The cytological features of NTTs in the developing wheat caryopsis were clearly elucidated. The results were as follows: NTTs in the wheat caryopsis include maternal transfer tissues that are composed of vascular bundle, chalaza and nucellar projection transfer cells, and endosperm transfer tissues that consist of the aleurone transfer cells, starchy endosperm transfer cells, and endosperm conducting cells. The initiation, development, and apoptosis of these NTTs revealed the pattern of temporal and spatial gradient and were closely coordinated with endosperm and embryo development. These results may give us a further understanding about the functions of NTTs and their relationships with endosperm and embryo development.