Exploring the Potential Pharmacologic Mechanism of Heterophyllin B in the Treatment of Esophageal Cancer by Network Pharmacology

This study used the method of network pharmacology to preliminarily predict the mechanism of Heterophyllin B(HB) inhibiting Esophageal Cancer(EC). We found the HB targets in the TCMSP and PuChem databases, and searched all EC-related targets in the GeneCards database. Taken the intersection of HB and EC as potential targets for inhibiting EC, and used Cytoscape 3.7.1 software to perform topological analysis on potential targets to obtain core targets. Used the start Analysisi function in the DAVID database to analyzed the biological process of the core target, and visualized it with the the R language tool. As a result, 75 potential targets for inhibiting EC were obtained, of which MMP9, MMP2, CCND1, STAT3, CXCR4, BDKRB1and PTGS2 were the main core targets. HB inhibits the occurrence of EC through Pathways in cancer, TNF signaling pathway, Bladder cancer, Small cell lung cancer, Rheumatoid arthritis related pathways, mainly involving proteolysis, collagen catabolic process, extracellular matrix disassembly, positive regulation of cell proliferation, positive regulation of cytosolic calcium ion concentration biological processes. This study initially revealed the molecular mechanism of HB inhibiting EC, and provided a reference for HB to expand new indications

Analysis of Oxoglaucine in the Treatment of Breast Cancer Based on Network Pharmacology and Bioinformatics

To explore the potential molecular mechanism of Oxoglaucine(OG) in the treatment of Breast Cancer(BC) based on network pharmacology and bioinformatics. TCMSP and SwissTargetPrediction databases search for OG Related targets, and GeneCards database finds all BC-related targets. Take the intersection of OG and BC as all potential targets that inhibit BC. All potential targets are topologically analyzed by Cytoscape 3.7.1 software, and finally the core target is obtained. The start analysisi function in the DAVID database performs bioinformatics analysis on all core targets, and further visualizes them with the help of R language tools. As a result, 104 potential targets were obtained, of which SRC, PIK3CA, EGFR, MTOR, ESR1, MAPK1, PTGS2, AR, and NOS3 were the main core targets. OG inhibits the occurrence of BC through Pathways in cancer, PI3K-Akt signaling pathway, Proteoglycans in cancer, ErbB signaling pathway, HIF-1 signaling pathway related pathways, mainly involving signal transduction, protein phosphorylation, negative regulation of apoptotic process, positive regulation of transcription from RNA polymerase II promoter, phosphatidylinositol-mediated signaling biological processes. This study initially reveals the molecular mechanism of OG inhibiting BC, which provides a reference for further research

Exploring the antidiabetic effect of lupenone in rats with type 1 diabetes and its underlying mechanism based on network pharmacology

Lupenone has been reported to possess numerous medicinal values and gives a positive antidiabetic effect. But the mechanism of preventing and treating type 1 diabetes has not been elucidated in type 1 diabetic rats. This study investigated the effects and mechanism of action of lupenone in preventing and treating type 1 diabetes by network pharmacology and diabetic rats. The blood glucose, glycosylated hemoglobin (HbA1c), insulin, and inflammatory factors in the pancreas of rats with type 1 diabetes were measured, and histopathological changes were observed after treatment with lupenone. The pharmacological network of ‘component-target-disease’ was constructed on diabetic rats. Gene function enrichment, the Kyoto Encyclopedia of Genes and Genomes pathway analysis, and molecular docking were performed. The results showed that lupenone can decrease fasting blood glucose and HbA1c levels, increase insulin content and interleukin (IL)-4, IL-10, and decrease IL-6, transforming growth factor β and tumor necrosis factor α levels in the pancreas. Furthermore, ten targets were identified, and 50 signal pathways closely related to type 1 diabetes and inflammation were screened by network pharmacology, including insulin resistance, type II diabetes, type I diabetes, insulin signal pathway, mitogen activated protein kinase (MAPK) signal pathway, and tumor necrosis factor (TNF) signal pathway. The docking affinity of potential targets and lupenone were between -3.3 and -9.8, among which caspase-3 (CASP3), cyclin-dependent kinase 4 (CDK4), inhibitor of kappaB kinase beta (IKBKB), transforming growth factor beta-1 (TGFB1), and TNF had high binding abilities. Thus, lupenone has the potential to be developed as a new drug for treating type 1 diabetes

Satellite-observed strong subtropical ocean warming as an early signature of global warming

Satellite observations covering the last four decades reveal an ocean warming pattern resembling the negative phase of the Pacific Decadal Oscillation. This pattern has therefore been widely interpreted as a manifestation of natural climate variability. Here, we re-examine the observed warming pattern and find that the predominant warming over the subtropical oceans, while mild warming or even cooling over the subpolar ocean, is dynamically consistent with the convergence and divergence of surface water. By comparison of observations, paleo-reconstructions, and model simulations, we propose that the observed warming pattern is likely a short-term transient response to the increased CO2 forcing, which only emerges during the early stage of anthropogenic warming. On centennial to millennial timescales, the subpolar ocean warming is expected to exceed the temporally dominant warming of the subtropical ocean. This delayed but amplified subpolar ocean warming has the potential to reshape the ocean-atmosphere circulation and threaten the stability of marine-terminating ice sheets

Therapeutic effects of STAT3 decoy oligodeoxynucleotide on human lung cancer in xenograft mice

<p>Abstract</p> <p>Background</p> <p>Signal transducer and activator of transcription 3 (STAT3) is usually constitutively activated in a variety of malignancies. Therefore, STAT3 may be a promising target for treatment of tumor cells. To explore the possibility of a double-stranded decoy oligodeoxynucleotide (ODN) targeted blocking STAT3 over-activated tumor cells, we, here, evaluate the efficacy of STAT3 decoy ODN on human lung cancer cells <it>in vitro </it>and <it>in vivo</it>.</p> <p>Methods</p> <p>A STAT3 decoy ODN was transfected into A549 lung cancer cell line <it>in vitro </it>by using lipofectamine. The flow cytometry and fluorescent microscopy were used to detect the transfection efficiency and the sub-cellular localization of STAT3 decoy ODN in A549 cells. Cell proliferation was determined by counting cell numbers and [³H]-thymidine uptake. Cell apoptosis was examined with Annexin V and propidum iodide by flow cytometry. The expression levels of STAT3 target genes were identified by RT-PCR and immunoblot. For <it>in vivo </it>experiment, A549 lung carcinoma-nude mice xenograft was used as a model to examine the effect of the STAT3 decoy by intratumoral injection. At the end of treatment, TUNEL and immunohistochemistry were used to examine the apoptosis and the expression levels of bcl-xl and cyclin D1 in tumor tissues.</p> <p>Results</p> <p>STAT3 decoy ODN was effectively transfected into A549 lung cancer cells and mainly located in nucleus. STAT3-decoy ODN significantly induced apoptosis and reduced [³H]-thymidine incorporation of A549 cells as well as down-regulated STAT3-target genes <it>in vitro</it>. STAT3 decoy ODN also dramatically inhibited the lung tumor growth in xenografted nude mice and decreased gene expression of bcl-xl and cyclin D1.</p> <p>Conclusion</p> <p>STAT3 decoy ODN significantly suppressed lung cancer cells <it>in vitro </it>and <it>in vivo</it>, indicating that STAT3 decoy ODN may be a potential therapeutic approach for treatment of lung cancer.</p

Integrated Sr isotope variations and global environmental changes through the Late Permian to early Late Triassic

New 87Sr/86Sr data based on 127 well-preserved and well-dated conodont samples from South China were measured using a new technique (LA-MC-ICPMS) based on single conodont albid crown analysis. These reveal a spectacular climb in seawater 87Sr/86Sr ratios during the Early Triassic that was the most rapid of the Phanerozoic. The rapid increase began in Bed 25 of the Meishan section (GSSP of the Permian–Triassic boundary, PTB), and coincided closely with the latest Permian extinction. Modeling results indicate that the accelerated rise of 87Sr/86Sr ratios can be ascribed to a rapid increase (>2.8×) of riverine flux of Sr caused by intensified weathering. This phenomenon could in turn be related to an intensification of warming-driven runoff and vegetation die-off. Continued rise of 87Sr/86Sr ratios in the Early Triassic indicates that continental weathering rates were enhanced >1.9 times compared to those of the Late Permian. Continental weathering rates began to decline in the middle–late Spathian, which may have played a role in the decrease of oceanic anoxia and recovery of marine benthos. The 87Sr/86Sr values decline gradually into the Middle Triassic to an equilibrium values around 1.2 times those of the Late Permian level, suggesting that vegetation coverage did not attain pre-extinction levels thereby allowing higher runoff

Smithian platform-bearing gondolellid conodonts from Yiwagou Section, northwestern China and implications for their geographic distribution in the Early Triassic

Abundant platform-bearing gondolellid conodonts, including Scythogondolella mosheri (Kozur and Mostler), Sc. phryna Orchard and Zonneveld, and Sc. cf. milleri (Müller), have been discovered from the Yiwagou Section of Tewo, together with Novispathodus waageni waageni (Sweet) and Nv. w. eowaageni Zhao and Orchard. This is the first report of Smithian platform-bearing gondolellids from the Paleo-Tethys region. In addition, Eurygnathodus costatus Staesche, E. hamadai(Koike), Parafurnishius xuanhanensis Yang et al., and the genera Pachycladina Staesche, Parachirognathus Clark, and Hadrodontina Staesche have also been recovered from Dienerian to Smithian strata at Yiwagou Section. Three conodont zones are established, in ascending order: Eurygnathodus costatus-E. hamadai Assemblage Zone, Novispathodus waageni-Scythogondolella mosheri Assemblage Zone, and the Pachycladina-Parachirognathus Assemblage Zone. The platform-bearing gondolellids were globally distributed just after the end-Permian mass extinction, but the formerly abundant Clarkina Kozur disappeared in the late Griesbachian. Platform-bearing gondolellids dramatically decreased to a minimum of diversity and extent in the Dienerian before recovering in the Smithian. Scythogondolella Kozur, probably a thermophilic and eurythermic genus, lived in all latitudes at this time whereas other genera did not cope with Smithian high temperatures and so became restricted to the high-latitude regions. However, the maximum temperature in the late Smithian likely caused the extinction of almost all platform-bearing gondolellids. Finally, the group returned to equatorial regions and achieved global distribution again in the cooler conditions of the late Spathian. We conclude that temperature (and to a lesser extent oxygen levels) exerted a strong control on the geographical distribution and evolution of platform-bearing gondolellids in the Early Triassic

A review of the Late Permian – Early Triassic conodont record and its significance for the end-Permian mass extinction

As a marine microfossil with a long-lasting fossil record stretching from the Cambrian to the Triassic, the tiny conodont plays an important role for the study of the end-Permian mass extinction. In the past few decades, numerous studies on Permian-Triassic conodonts have been published. This paper summarizes the progress made on high-resolution conodont biostratigraphy, timing of the mass extinction across the Permian-Triassic Boundary, conodont apparatus and phylogeny, conodont size variation, conodont oxygen isotope as well as other isotopes and chemical elements. Finally, future perspectives are also discussed

Screening compounds for treating the diabetes and COVID-19 from Miao medicine by molecular docking and bioinformatics

Both diabetes and Corona Virus Disease 2019 (COVID-19) are seriously harmful to human health, and they are closely related. It is of great significance to find drugs that can simultaneously treat diabetes and COVID-19. Based on the theory of traditional Chinese medicine for treating COVID-19, this study first sorted out the compounds of Guizhou Miao medicine with “return to the lung channel” and “clear heat and detoxify” effects in China. The active components against COVID-19 were screened by molecular docking with SARS-CoV-2 PLpro and angiotensin-converting enzyme II as targets. Furthermore, the common target dipeptidyl peptidase 4 (DPP4) of diabetes and COVID-19 was used as a screening protein, and molecular docking was used to obtain potential components for the treatment of diabetes and COVID-19. Finally, the mechanism of potential ingredients in the treatment of diabetes and COVID-19 was explored with bioinformatics. More than 80 kinds of Miao medicine were obtained, and 584 compounds were obtained. Further, 110 compounds against COVID-19 were screened, and top 6 potential ingredients for the treatment of diabetes and COVID-19 were screened, including 3-O-β-D-Xylopyranosyl-(1-6)-β-D-glucopyranosyl-(1-6)-β-D-glucopyranosyl oleanolic acid 28-O-β-D-glucopyranosyl ester, Glycyrrhizic acid, Sequoiaflavone, 2-O-Caffeoyl maslinic acid, Pholidotin, and Ambewelamide A. Bioinformatics analysis found that their mechanism of action in treating diabetes and COVID-19 may be related to regulating the expression of DPP4, angiotensin II type 1 receptor, vitamin D receptor, plasminogen, chemokine C–C-motif receptor 6, and interleukin 2. We believe that Guizhou Miao medicine is rich in potential ingredients for the treatment of diabetes and COVID-19

Exploring the Potential Pharmacologic Mechanism of Heterophyllin B in the Treatment of Esophageal Cancer by Network Pharmacology

This study used the method of network pharmacology to preliminarily predict the mechanism of Heterophyllin B(HB) inhibiting Esophageal Cancer(EC). We found the HB targets in the TCMSP and PuChem databases, and searched all EC-related targets in the GeneCards database. Taken the intersection of HB and EC as potential targets for inhibiting EC, and used Cytoscape 3.7.1 software to perform topological analysis on potential targets to obtain core targets. Used the start Analysisi function in the DAVID database to analyzed the biological process of the core target, and visualized it with the the R language tool. As a result, 75 potential targets for inhibiting EC were obtained, of which MMP9, MMP2, CCND1, STAT3, CXCR4, BDKRB1and PTGS2 were the main core targets. HB inhibits the occurrence of EC through Pathways in cancer, TNF signaling pathway, Bladder cancer, Small cell lung cancer, Rheumatoid arthritis related pathways, mainly involving proteolysis, collagen catabolic process, extracellular matrix disassembly, positive regulation of cell proliferation, positive regulation of cytosolic calcium ion concentration biological processes. This study initially revealed the molecular mechanism of HB inhibiting EC, and provided a reference for HB to expand new indications