Given that the biomechanical theory cannot well explain the therapeutic effect of fan-ashi point (a special site that may relieve pain by pressing), the skeletal muscle tension is adopted and it is attempted to interpret the mechanism of the curative effect and the effect onset of fan-ashi point. It is viewed that the longitudinal tension conduction and transverse tension conduction pathways of skeletal muscle are the material basis of the effect onset of fan-ashi point. Hence, acupuncture at fan-ashi point may alter the longitudinal or transverse tension conduction of skeletal muscle to relieve muscle and tendon pain.
Equine FSH (eFSH) and eCG are members of the glycoprotein hormone family. These proteins are heterodimeric, composed of noncovalently associated α and β subunits. We have previously reported that recombinant eCG has potent LH- and FSH-like activities and that the oligosaccharide at Asn56 of the α subunit plays an indispensable role in expressing LH- but not FSH-like activity. In the present study, we cloned eFSH β subunit cDNA and expressed wild-type recombinant eFSH and a partially deglycosylated mutant FSH (eFSH α56/β) to investigate the biological role of the oligosaccharide at Asn56 in FSH activity. The wild-type eFSH and eCG stimulated estradiol production in a dose-dependent manner in the primary cultures of rat granulosa cells, indicating that these equine gonadotropins have FSH activity. Partially deglycosylated eCG (eCG α56/β) also stimulated estradiol production, confirming that the FSH-like activity of eCG is resistant to the removal of the N-linked oligosaccharide. Partially deglycosylated eFSH (eFSH α56/β), however, did not show any FSH activity, indicating that the oligosaccharide at Asn56 was necessary for eFSH. Thus, FSH-like activities of two gonadotropins, eCG and eFSH, are evoked through the distinct molecular mechanisms regarding the biological role of oligosaccharide at Asn56 of the α subunit.
Abstract The ATP-adenosine pathway has emerged as a promising target for cancer therapy, but challenges remain in achieving effective tumor control. Early research focused on blocking the adenosine generating enzyme CD73 and the adenosine receptors A2AR or A2BR in cancer. However, recent studies have shown that targeting CD39, the rate-limiting ecto-enzyme of the ATP-adenosine pathway, can provide more profound anti-tumor efficacy by reducing immune-suppressive adenosine accumulation and increasing pro-inflammatory ATP levels. In addition, combining CD39 blocking antibody with PD-1 immune checkpoint therapy may have synergistic anti-tumor effects and improve patient survival. This review will discuss the immune components that respond to CD39 targeting in the tumor microenvironment. Targeting CD39 in cancer has been shown to not only decrease adenosine levels in the tumor microenvironment (TME), but also increase ATP levels. Additionally, targeting CD39 can limit the function of Treg cells, which are known to express high levels of CD39. With phase I clinical trials of CD39 targeting currently underway, further understanding and rational design of this approach for cancer therapy are expected.
INTRODUCTION:LncRNA is reported to have important role in diabetic nephropathy (DN).Here, we aim to identify key lncRNAs of DN using bioinformatics and systems biological methods.METHODS: Five microarray data sets from Gene Expression Omnibus (GEO) database were included.Probe sets were re-annotated.In the training set, differential expressed genes (DEGs) were identified.Weighted gene co-expression network analysis (WGCNA) was constructed to screen diabetic-related hub genes and reveal their potential biological function.Two more human data sets and mouse data sets were used as validation sets.RESULTS: A total of 424 DEGs, including 10 lncRNAs, were filtered in the training data set.WGCNA and enrichment analysis of hub genes showed that inflammation and metabolic disorders are prominent in DN.Three key lncRNAs (NR_130134.1,NR_029395.1 and NR_038335.1)were identified.These lncRNAs are also differently expressed in another two human data sets.Functional enrichment of the mouse data sets showed consistent changes with that in human, indicating similar changes in gene expression pattern of DN and confirmed confidence of our analysis.CONCLUSIONS: Inflammation and metabolic disorders are prominent in DN.We identify three lncRNAs that are involved in these processes possibly by interacting with co-expressed mRNAs.
Abstract Objective To explore the mechanism of the Lichong Shengsui Drink (including Panax Ginseng, Epimrdii Herba, Sparganii Rhizoma, Curcumae Rhizoma, Hedysarum Multijugum Maxim, Fritillariae Thunbrgii Bulbus, Cervus nippon and Bigflower Cape Jasmine) in the treatment of ovarian cancer by network pharmacology and molecular docking technology. Methods TCMSP, HERB(http://herb.ac.cn/), SwissTargetPrediction, and TCM-Batman were used to retrieve the chemical components and action targets of drugs; the DEGs of ovarian cancer gene chip: GSE105437, GSE66957, GSE146533 were obtained by GEO2R. The common genes of DEGs and active ingredient targets were obtained by the Venn method. The PPI network of the common genes obtained by STRING, and the network of active ingredients and its target were visualized by Cytoscape 3.10.2. The hub genes of the PPI network and hub ingredient of the active ingredient targets network were obtained by Cytohubba. GO and KEGG enrichment analyses were completed for the ingredient targets, shared genes, and hub proteins. Finally, The structures of common targets and core components were downloaded from PubChem and PDB and were then molecular docked by CB-dock2. Results A total of 90 effective components of this compound were screened out which have 3514 target genes, 2534 DEGs of the ovarian cancer gene chip of GSE105437, GSE66957, and GSE146533 were picked out: they have 185 common genes in total by Venn. The PPI network of the 185 common genes and the ingredient-targets network were then constructed, as well, and hub genes and hub ingredients were identified by Cytohubba. Top 10 genes of ESR1, EGFR, CXCR4, KIT, AKT1, PGR, CD24, SRC, SNAI2, STAT3 and top 10 ingredients of Adenosine triphosphate, 17-beta-estradiol, 17alpha-estradiol, estrone, 11-eicosenoicacid, arachidonate, crocetin, cholesterol, galactosamine, beta-sitosterol were obtained. The first four ingredients were widely perceived as connected to the hub genes. However, 11-eicosenoicacid, arachidonate, and crocetin were still yet not known. With the help of molecular docking technology; the three compounds had excellent binding properties with the hub genes.KEGG pathways of the hub genes were associated with PIP3 activates AKT signaling, intracellular signaling by second messengers, diseases of signal transduction, and so on; and the GO process was associated with cell differentiation, cellular developmental process, cellular response to chemical stimulus, and so on. Conclusion Our study provided valuable information that Lichong Shengsui Drink might regulate the expression of ESR1, EGFR, CXCR4, and so on for the therapy of ovarian cancer in the form of multi-biological process, multi-factors, multi-pathways, and multi-targets.
To address the water-related issues faced by humans, the planning and construction of dams, water diversion projects, and other water infrastructures have been continuously adopted by decision makers worldwide. This is especially the case for the Yalong River Basin (YRB) in China, which is expected to be one of the most regulated rivers due to reservoir construction and the planned South-to-North Water Diversion project. To understand the potential impact of these water infrastructures on the water resources and hydropower production of the basin and downstream areas, we employ a land surface–hydrologic model with explicit representations of dam operation and water diversions in order to quantify the impact of reservoir operation and water diversion on the future water and energy security of the YRB. In particular, a conceptual reservoir operation scheme and a hydropower-optimized reservoir operation scheme are employed to predict the future release, storage and hydropower generation of the YRB, respectively. Results indicate that reservoirs can have noticeable, cumulative effects in enhancing the water security by reducing the wet season streamflow by 19% and increasing the dry season streamflow by 66%. The water diversion can result in an overall decrease in the streamflow, while the downstream reservoirs are expected to fully mitigate the decline in the dry season streamflow. The hydropower production is likely to decrease by 16% and 10% with conventional and optimized operation schemes, respectively, which suggests that the adaptation of operation rules alone cannot reverse the decline in the electricity production. Our findings can provide implications for sustainable water resource management.
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