Based on the prognosis model of immunogenes, the prognosis model was constructed to predict the invasion of immune genes and immune cells related to primary liver cancer and its experimental validation.

Background: Primary liver cancer (PLC) is a prevalent malignancy of the digestive system characterized by insidious symptom onset and a generally poor prognosis. Recent studies have highlighted a significant correlation between the initiation and prognosis of liver cancer and the immune function of PLC patients. Purpose: Revealing the expression of PLC-related immune genes and the characteristics of immune cell infiltration provides assistance for the analysis of clinical pathological parameters and prognosis of PLC patients. Methods: PLC-related differentially expressed genes (DEGs) with a median absolute deviation (MAD > 0.5) were identified from TCGA and GEO databases. These DEGs were intersected with immune-related genes (IRGs) from the ImmPort database to obtain PLC-related IRGs. The method of constructing a prognostic model through immune-related gene pairs (IRGPs) is used to obtain IRGPs and conduct the selection of central immune genes. The central immune genes obtained from the selection of IRGPs are validated in PLC. Subsequently, the relative proportions of 22 types of immune cells in different immune risk groups are evaluated, and the differential characteristics of PLC-related immune cells are verified through animal experiments. Results: Through database screening and the construction of an IRGP prognosis model, 84 pairs of IRGPs (P < 0.001) were ultimately obtained. Analysis of these 84 IRGPs revealed 11 central immune genes related to PLC, showing differential expression in liver cancer tissues compared to normal liver tissues. Results from the CiberSort platform indicate differential expression of immune cells such as naive B cells, macrophages, and neutrophils in different immune risk groups. Animal experiments demonstrated altered immune cell proportions in H22 tumor-bearing mice, validating findings from peripheral blood and spleen homogenate analyses. Conclusion: Our study successfully predicted and validated PLC-related IRGs and immune cells, suggesting their potential as prognostic indicators and therapeutic targets for PLC.

Overexpression of MiR-633 Suppresses the Tumorigenicity of Gastric Cancer Cells and Induces Apoptosis by Targeting MAPK1.

OBJECTIVE: MicroRNA (miRNA/miR)-633 is dysregulated in several types of cancers and is involved in tumorigenesis. However, the function and role of this miRNA in gastric cancer (GC) are not fully understood. The aim of the present study was to evaluate miR-633 expression in GC cell lines and in GC tissue vs. adjacent normal tissue, and to determine its association with clinicopathological data. This work was extended to investigate the effects of miR-633 overexpression on tumor cells in vitro. METHODS: Reverse transcription-quantitative PCR (RT-qPCR) was used to detect and compare the expression level of miR-633 in GC cells, as well as in GC and normal adjacent tissue samples. The clinical significance of miR-633 was also analyzed. MiR-633 lentivirus (LV-miR-633) and negative control lentivirus (LV-NC) were generated and used to transduce SGC-7901 and HGC-27 GC cells in order to analyze the effect of miR-633 on their phenotype. The effects of miR-633 overexpression on GC cell proliferation, apoptosis, migration and invasion were investigated. The target gene of miR-633 was predicted, then confirmed using a dual luciferase reporter gene assay, RT-qPCR and Western blotting. RESULTS: MiR-633 was significantly downregulated in GC cell lines, as well as in GC tissue compared with adjacent normal tissue. Moreover, miR-633 expression was associated with the tumor/node/metastasis (TNM) stage, invasion depth, Borrmann classification and lymph node metastasis (P<0.05). Compared with the LV-NC group, transduction with LV-miR-633 reduced the proliferation, the number of clones, the wound healing rate, the number of invading cells and the number of cells in the G1 phase of the cell cycle (P<0.01). LV-miR-633 also increased the apoptosis rate (P<0.01). The expression level of mitogen-activated protein kinase (MAPK) 1, high-mobility group box 3 (HMGB3), claudin 1 (CLDN1) and MAPK13 were downregulated in LV-miR-633-transduced cells (P<0.01). The dual luciferase reporter assay confirmed that the 3'-untranslated region of MAPK1 was the target site of miR-633 (P<0.01). CONCLUSION: MiR-633 acts as a tumor suppressor in GC, and its expression level is associated with TNM stage, invasion depth, Borrmann type and lymph node metastasis. Overexpression of miR-633 inhibits the proliferation and migration of GC cells and induces apoptosis and cell cycle arrest at the in G1 phase. In addition, miR-633 negatively regulates the expression of MAPK1, HMGB3, CLDN1 and MAPK13 and directly targets MAPK1.

Potential Chemoprevention of Paeoniflorin in Colitis-Associated Colorectal Cancer by Network Pharmacology, Molecular Docking, and In Vivo Experiment.

Chronic inflammation plays a positive role in the development and progression of colitis-associated colorectal cancer (CAC). Medicinal plants and their extracts with anti-inflammatory and immunoregulatory properties may be an effective treatment and prevention strategy for CAC. This research aimed to explore the potential chemoprevention of paeoniflorin (PF) for CAC by network pharmacology, molecular docking technology, and in vivo experiments. The results showed that interleukin-6 (IL-6) is a key target of PF against CAC. In the CAC mouse model, PF increased the survival rate of mice and decreased the number and size of colon tumors. Moreover, reduced histological score of colitis and expression of Ki-67 and PCNA were observed in PF-treated mice. In addition, the chemoprevention mechanisms of PF in CAC may be associated with suppression of the IL-6/STAT3 signaling pathway and the IL-17 level. This research provides experimental evidence of potential chemoprevention strategies for CAC treatment.

[Effect and mechanism of Jingqi Yukui Capsules on gastric ulcer mucosa healing quality: based on network pharmacology and animal experiment].

This study aims to identify the active components and the mechanism of Jingqi Yukui Capsules(JQYK) in the treatment of gastric ulcer based on network pharmacology, and verify some key targets and signaling pathways through animal experiment. To be specific, first, the active components and targets of JQYK were retrieved from a Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine(BATMAN-TCM) and Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), and the targets of gastric ulcer from GeneCards and Online Mendelian Inheritance in Man(OMIM) with the search term "gastric ulcer". The common targets of the two were the potential targets of the prescription for the treatment of the di-sease. Then, protein-protein interaction(PPI) network of key targets were constructed based on STRING and Cytoscape 3.7.2, followed by Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment by matescape database and pathway visualization by Omicshare. For the animal experiment, the improved method of Okabe was used to induce gastric ulcer in rats, and the model rats were classified into the model group, JQYK high-dose(JQYK-H), medium-dose(JQYK-M), and low-dose(JQYK-L) groups, Anweiyang Capsules(WYA) group, and Rabeprazole Sodium Enteric Capsules(RBPZ) group. Normal rats were included in the blank group. Rats in the blank group and model group were given distilled water and those in the administration groups received corresponding drugs. Then gastric ulcer healing in rats was observed. The changes of the gastric histomorphology in rats were evaluated based on hematoxylin-eosin(HE) staining, and the content of inducible nitric oxide synthase(iNOS) in rat gastric tissue was detected with Coomassie brilliant blue method. The mRNA and protein levels of some proteins in rat gastric tissue were determined by real-time quantitative polymerase chain reaction(RT-qPCR) and Western blot(WB) to further validate some key targets and signaling pathways. A total of 206 active components and 535 targets of JQYK, 1 305 targets of gastric ulcer, and 166 common targets of the disease and the drug were yielded. According to PPI analysis and KEGG pathway enrichment analysis, multiple key targets, such as interleukin-6(IL-6), tumor necrosis factor(TNF), mitogen-activated protein kinase 1(MAPK1), MAPK3, and MAPK14, as well as nuclear factor kappa-B(NF-κB) signaling pathway, IL-17 signaling pathway, and leukocyte transendothelial migration in the top 20 key signaling pathways were closely related to inflammation. The key protein p38 MAPK and NF-κB signaling pathway were selected for further verification by animal experiment. The gastric ulcer in the JQYK-H group recovered nearly to the level in the blank group, with significant decrease in the content of iNOS in rat gastric tissue and significant reduction in the mRNA and phosphorylation levels of p38 MAPK and the mRNA and protein levels of NF-κB p65 in rat gastric tissue. The results indicated that JQYK can inhibit the phosphorylation of the key protein p38 MAPK and the expression of NF-κB p65 in the NF-κB signaling pathway, thereby exerting the anti-inflammatory effect and effectively improving the quality of gastric ulcer healing in rats. Thus, the animal experiment result verifies some predictions of network pharmacology.

Improved two-step optimization procedure used for designing an apodizer and Lyot stop in the Lyot coronagraph.

The Lyot coronagraph is a widely known astronomical instrument used to realize direct imaging of exoplanets, and designing transmittance of an apodizer and Lyot stop is the key to obtaining high-contrast imaging. In this paper a new (to the best of our knowledge) optimization procedure used to design the apodizer and Lyot stop in the Lyot coronagraph is proposed. A two-step optimization program is established to obtain the optimum transmittance of an apodizer and Lyot stop in a sequential way. By using the optimized apodizer and Lyot stop obtained through the proposed optimization procedure, both the stellar light and its diffraction light could be strongly suppressed. Numerical results indicate that such an optimized Lyot coronagraph can produce a 1e-10 extinction of the stellar light near the diffraction limit (1.59λ/D), and a high contrast imaging of 1e-07 could still be obtained even with the influence of light intensity of planets themselves. In addition, the two-step optimization procedure brings in two benefits. First, the two-step optimization is approximately 1000 times faster than the joint optimization method [J. Astron. Telesc. Instrum. Syst.2, 011012 (2016)2329-412410.1117/1.JATIS.2.1.011012]. Second, the optimum transmittance of the Lyot stop is binary, and therefore, the requirements of the production process are reduced, resulting in a greatly reduced cost. At the same time, the performance of the optimized Lyot coronagraph is also analyzed in the case of a monochromatic light incident and bandwidth light incident, and the effect of the diameter of the Lyot stop on the results is also discussed in this paper, which makes sense when designing a coronagraph.

[Intervention of Qi-activating and Spleen-strengthening Herbs on Ca2+/CaMK II Signaling Pathways Key Factors in Skeletal Muscle Tissue of Rats with Spleen-qi Deficiency].

OBJECTIVE: To observe changes of [Ca2+]i concentration and CaM, CaMK II and p-CaMK II of Ca2+/CaMK II signaling pathways in skeletal muscle tissue of rats with spleen-qi deficiency and intervention of Sijunzi decoction and extract of Hedysarum polybotrys. METHODS: Rats were randomized into four groups: normal control group, spleen-qi deficient model group, extract from Hedysarum polybotrys group and Sijunzi decoction group, ten rats in each group. After the spleen-qi deficient models were built by comprehensive application of rhubarb, exhaustive and hungry methods, and treatment groups were treated with extract from Hedysarum polybotrys at 6 g/(kg . d) or Sijunzi decoction at 20 g/(kg . d) for 21 d. Then, general existence,gastrointestinal hormones GAS and MOT levels, and activities of Na+-K+-ATPase and Ca2+-Mg2+-ATPase of skeletal muscle were evaluated. Also, confocal laser technology was used to test cellular[Ca2+]i concentrations in skeletal muscle and Western blotting technique was used to test CaM, CaMK II and p-CaMK 11 expression in intestinal tissue of spleen-qi deficient model rats. RESULTS: Compared with normal group, general condition was poor, levels of GAS and MOT decreased (P <0. 01), activities of Na+-K+-ATPase and Ca2+-Mg2+-ATPase, [Ca2+]i concentration as well as expression of CaM, CaMK II and p-CaMK II in skeletal muscle decreased significantly (P < 0. 01) in spleen-qi deficienct model rats. Compared with model group, general condition improved significantly, as well as level of MOT in intestinal increased (P <0. 05) in the rats of extract from Hedysarum polybotrys group and Sijunzi decoction group,while level of GAS increased in intestinal(P <0. 05) in the rats of Sijunzi decoction group; Moreover, activities of Na+-K+-ATPase and Ca2+-Mg2+-ATPase as well as [Ca2+]i concentration and expression of CaM and CaMK II in skeletal muscle tissue increased (P < 0. 05) in the rats of extract from Hedysarum polybotrys group and Sijunzi decoction group, while p-CaMK II in skeletal muscle tissue increased in the rats of Sijunzi decoction group (P < 0. 05). CONCLUSION: Sijunzi decoction and extract of Hedysarum polybotrys can be applied to treat spleen-qi deficiency syndrome through the mechanism of regulating GAS and MOT secretion and raising expression of Ca2+ /CaM signaling pathways key factors in skeletal muscle tissue. Sijunzi decoction has the better effect

[Study on interference effect of Sijunzi decoction on brain-gut CaM/CaMK II of spleen Qi deficiency syndrome rats].

OBJECTIVE: To observe the dynamic time-phase expressions of key genes of brain-gut CaM signal pathway of spleen Qi deficiency rats and the intervention effect of Sijunzi decoction. METHOD: Male Wistar rats were randomly divided into the normal control group, model 14 d, 21 d, 28 d groups, and Sijunzi decoction 14 d, 21 d, 28 d groups. Except for the normal control group, the remaining groups were included into the spleen Qi deficiency model with the bitter cold breaking Qi method (ig 7.5 g · kg⁻¹ · d⁻¹ of Rheum officinale, Fructus aurantii immaturus, Magnolia officinalis preparation) and the exhaustive swimming method. On the 7th day after the modeling, the Sijunzi decoction groups were orally administered with Sijunzi decoction 20 g · kg⁻¹ · d⁻¹. The expressions of key genes CaM/CaMK II of CaM signaling pathway in hippocampus and intestine at different time points by immunohistochemical method and Western blot. At the same time, the intervention effect of Sijunzi decoction on spleen Qi deficiency rats and its mechanism were analyzed. RESULT: Spleen Qi deficiency rats showed higher intestinal CaM/CaMK II expression and lower hippocampus CaM/CaMK II expression than normal rats (P < 0.05, P < 0.01). After the treatment of Sijunzi decoction, spleen Qi deficiency rats showed reduction in intestinal CaM/CaMK II expression and increase in hippocampus CaM/CaMK II expression (P < 0.05, P < 0.01). CONCLUSION: The formation of spleen Qi deficiency syndrome may be related to the high expression of CaM/CaMK II in small intestine tissues and its low expression in hippocampus tissues. Sijunzi decoction may achieve the therapeutic effect in spleen Qi deficiency syndrome by reducing the CaM/CaMK II expression in intestinal tissues and increasing it in hippocampus tissues.

Radix Hedysari polysaccharide suppresses lipid metabolism dysfunction in a rat model of non­alcoholic fatty liver disease via adenosine monophosphate­activated protein kinase pathway activation.

Oxidative stress and excess hepatic lipid accumulation contribute to non­alcoholic fatty liver disease. Radix Hedysari polysaccharides (RHP) have attracted interest due to their antioxidant properties and immunomodulatory effects. However, the effect of RHP on hepatic lipid metabolism remains to be elucidated. In the present study, the response of Sprague­Dawley rat livers to a high­fat diet and RHP treatment was investigated by evaluating body weight, liver histology, hepatic lipid content, adenosine monophosphate­activated protein kinase (AMPK) activity and lipid metabolism gene transcriptional profiles. The present study demonstrated that RHP ameliorated lipid metabolism disorders, regulated hepatic lipid content, improved liver inflammation and damage, activated AMPK via phosphorylation, upregulated peroxisome proliferator­activated receptor α and downregulated the mRNA expression of sterol regulatory element binding protein­1c in rat livers, which reduced lipogenesis and increased lipolysis. Taken together, these results suggested that RHP effectively ameliorates lipid metabolism disorders in rat livers; thus, RHP may be a potential therapeutic agent in the prevention of hepatic steatosis.