Uncovering the mechanism of Naoxintong capsule against hypertension based on network analysis and in vitro experiments.

Naoxintong capsule (NXT) is a clinical drug for the treatment of cardiovascular diseases, but its pharmacological mechanism against hypertension remains unclear. Data concerning the compounds and targets of NXT were obtained from the TCMSP and DrugBank, whereas data concerning hypertension-related genes were obtained from DisGeNET. The network was analyzed and established by STRING and Cytoscape, and function enrichment was analyzed by GO and KEGG analysis. Molecular docking was performed to analyze the interaction between ingredients and targets, cellular activity was evaluated by MTT assay, and RT-qPCR and western blot were used to evaluate the expressions of related genes. The results showed that 146 active therapeutic components can target hypertension-related genes, and we found that core genes were mainly involved in the metabolism of lipids, lipopolysaccharides, the inflammatory signaling pathway, and the oxidative stress pathway. In addition, there was high affinity between the components of NXT and targets of hypertension, where the former can increase cell viability and reduce the expressions of NOX4, MCP-1, BAX, TNF-α and IL-1ß. Moreover, NXT inhibited the expressions of IL-6 and Fis1, as well as increased the expression of MCL-1. These results revealed the active compounds, hypertension targets, signaling pathways, and molecular mechanisms of NXT for treating hypertension, offering references for the clinical application of NXT and the treatment of hypertension.

Nanomaterial-based CT contrast agents and their applications in image-guided therapy.

Computed tomography (CT), a diagnostic tool with clinical application, comprehensive coverage, and low cost, is used in hospitals worldwide. However, CT imaging fails to distinguish soft tissues from normal organs and tumors because their mass attenuation coefficients are similar. Various CT contrast agents have been developed in recent years to improve the sensitivity and contrast of imaging. Here, we review the progress of nanomaterial-based CT contrast agents and their applications in image-guided therapy. The CT contrast agents are classified according to their components; gold (Au)-based, bismuth (Bi)-based, lanthanide (Ln)-based, and transition metal (TM)-based nanomaterials are discussed. CT image-guided therapy of diseases, including photothermal therapy (PPT), photodynamic therapy (PDT), chemotherapy, radiotherapy (RT), gas therapy, sonodynamic therapy (SDT), immunotherapy, starvation therapy, gene therapy (GT), and microwave thermal therapy (MWTT), are reviewed. Finally, the perspectives on the CT contrast agents and their biomedical applications are discussed.

Blueberry anthocyanins extract attenuated diabetic retinopathy by inhibiting endoplasmic reticulum stress via the miR-182/OGG1 axis.

BACKGROUND: Previous studies have found that blueberry anthocyanin extract (BAE) could prevent diabetic retinopathy (DR) development, but the underlying molecular mechanism is still a mystery. METHODS: Human retinal pigment epithelium cell line ARPE-19 cells were exposed to high concentration glucose (H-Glu) with 25 mM for 24 h, and the cell viability and apoptosis were analyzed by MTT assay and flow cytometry, respectively. The endoplasmic reticulum stress (ERS) markers were determined by western blotting. Dual luciferase assay was applied to investigate the relationship between miR-182 and 8-oxoguanine-DNA glycosylase (OGG1). Furthermore, experiments in vivo were also performed to confirm the function of BAE in DR. RESULTS: The increase of apoptosis, reactive oxygen species (ROS) level and ERS in ARPE-19 cells induced by H-Glu was notably restored by BAE. Meanwhile, BAE greatly inhibited H-Glu-induced miR-182 expression in ARPE-19 cells, and OGG1 was identified to be one of the downstream target moleculars of miR-182. Furthermore, miR-182 overexpression or OGG1 knockdown restored the impact of BAE on H-Glu-treated APRE-19 cells. Even more important, BAE was further confirmed to alleviated the development of DR in diabetes rat models. CONCLUSIONS: BAE significantly inhibited the progression of DR via molecular regulation function between miR-182/OGG1 axis and ROS/ERS.

DL-3-n-butylphthalide ameliorates diabetes-associated cognitive decline by enhancing PI3K/Akt signaling and suppressing oxidative stress.

DL-3-n-Butylphthalide (DL-NBP), a small molecular compound extracted from the seeds of Apium graveolens Linn (Chinese celery), has been shown to exert neuroprotective effects due to its anti-inflammatory, anti-oxidative and anti-apoptotic activities. DL-NBP not only protects against ischemic cerebral injury, but also ameliorates vascular cognitive impairment in dementia patients including AD and PD. In the current study, we investigated whether and how DL-NBP exerted a neuroprotective effect against diabetes-associated cognitive decline (DACD) in db/db mice, a model of type-2 diabetes. db/db mice were orally administered DL-NBP (20, 60, 120 mg· kg-1· d-1) for 8 weeks. Then the mice were subjected to behavioral test, their brain tissue was collected for morphological and biochemical analyses. We showed that oral administration of DL-NBP significantly ameliorated the cognitive decline with improved learning and memory function in Morris water maze testing. Furthermore, DL-NBP administration attenuated diabetes-induced morphological alterations and increased neuronal survival and restored the levels of synaptic protein PSD95, synaptophysin and synapsin-1 as well as dendritic density in the hippocampus, especially at a dose of 60 mg/kg. Moreover, we revealed that DL-NBP administration suppressed oxidative stress by upregulating Nrf2/HO-1 signaling, and increased brain-derived neurotrophic factor (BDNF) expression by activating PI3K/Akt/CREB signaling in the hippocampus. These beneficial effects of DL-NBP were observed in high glucose-treated PC12 cells. Our results suggest that DL-NBP may be a potential pharmacologic agent for the treatment of DACD.

Taurochenodeoxycholic acid mediates cAMP-PKA-CREB signaling pathway.

Taurochenodeoxycholic acid (TCDCA) is one of the main effective components of bile acid, playing critical roles in apoptosis and immune responses through the TGR5 receptor. In this study, we reveal the interaction between TCDCA and TGR5 receptor in TGR5-knockdown H1299 cells and the regulation of inflammation via the cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA)-cAMP response element binding (CREB) signal pathway in NR8383 macrophages. In TGR5-knockdown H1299 cells, TCDCA significantly activated cAMP level via TGR5 receptor, indicating TCDCA can bind to TGR5; in NR8383 macrophages TCDCA increased cAMP content compared to treatment with the adenylate cyclase (AC) inhibitor SQ22536. Moreover, activated cAMP can significantly enhance gene expression and protein levels of its downstream proteins PKA and CREB compared with groups of inhibitors. Additionally, TCDCA decreased tumour necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), IL-6, IL-8 and IL-12 through nuclear factor kappa light chain enhancer of activated B cells (NF-κB) activity. PKA and CREB are primary regulators of anti-inflammatory and immune response. Our results thus demonstrate TCDCA plays an essential anti-inflammatory role via the signaling pathway of cAMP-PKA-CREB induced by TGR5 receptor.

Potential Mechanisms of Action of Curcumin for Cancer Prevention: Focus on Cellular Signaling Pathways and miRNAs.

Despite significant progressions in treatment modalities over the last decade, either cancer incidence or mortality is continuously on the rise throughout the world. Current anticancer agents display limited efficacy, accompanied by severe side effects. In order to improve therapeutic outcomes in patients with cancer, it is crucial to identify novel, highly efficacious pharmacological agents. Curcumin, a hydrophobic polyphenol extracted from turmeric, has gained increasing attention due to its powerful anticancer properties. Curcumin can inhibit the growth, invasion and metastasis of various cancers. The anticancer mechanisms of curcumin have been extensively studied. The anticancer effects of curcumin are mainly mediated through its regulation of multiple cellular signaling pathways, including Wnt/ß-catenin, PI3K/Akt, JAK/STAT, MAPK, p53 and NF-ĸB signaling pathways. Moreover, curcumin also orchestrates the expression and activity of oncogenic and tumor-suppressive miRNAs. In this review, we summarized the regulation of these signaling pathways by curcumin in different cancers. We also discussed the modulatory function of curcumin in the downregulation of oncogenic miRNAs and the upregulation of tumor-suppressive miRNAs. An in-depth understanding of the anticancer mechanisms of curcumin will be helpful for developing this promising compound as a therapeutic agent in clinical management of cancer.

Hyperbaric oxygen treatment reduced the lung injury of type II decompression sickness.

OBJECTIVE: To detect the ultrastructural changes in rabbits with type II decompression sickness (DCS), and study the therapeutic effects of hyperbaric oxygen (HBO). METHODS: Twenty-seven male New Zealand rabbits were randomly divided equally into the DCS group, HBO treatment group and control group. Experimental models of each group were prepared. Lung apex tissues were harvested to prepare paraffin- and EPON812-embedded tissues. RESULTS: In the DCS group, macroscopic and histological examination revealed severe and rapid damage to lung tissue. Ultrastructural examination revealed exudation of red blood cells in the alveolar space. Type I alveolar epithelial cells exhibited retracted cell processes and swollen mitochondria, and type II cells showed highly swollen mitochondria and decrease in cytoplasmic lamellar bodies. Dilatation and congestion of capillary vessels were accompanied by swelling of endothelial cells and incomplete basement membrane. In the HBO treatment group, the findings were somewhat similar to those in the DCS group, but the extent of damage was lesser. Only a small amount of tiny bubbles could be seen in the blood vessels. Type I alveolar epithelia cells and endothelial cells of the capillaries illustrated slight shortening of cells, swollen cytoplasm and decreased cell processes. Type II alveolar epithelial cells showed slight swelling of the mitochondria, decreased vacuolar degeneration of lamellar bodies, and increase in the number of free ribosomes. CONCLUSIONS: Our microscopic and ultrastructural findings confirm that the lung is an important organ affected by DCS. We also confirmed that HBO can alleviate DCS-induced pulmonary damage.

Correlation between chemosensitivity to anticancer drugs and telomerase reverse transcriptase mRNA expression in gastric cancer.

BACKGROUND: The determination of sensitive chemotherapy drugs for gastric cancer (GC) is one of the greatest challenges of adjuvant therapy. Here we evaluated the chemosensitivity of GC to anticancer drugs and the telomerase reverse transcriptase (hTERT) mRNA expression, and investigated the relationship of them. METHODS: The GC cells which were collected from 68 patients with primary GC were primary cultured. The chemosensitivity of GC cells to anticancer drugs was evaluated successfully using the MTT assay for 60 cases of GC cells, and the hTERT mRNA expression was examined in 60 cases of GC tissues and corresponding normal gastric mucosa and 6 cases of chronic superficial gastritis mucosa by in situ hybridization. RESULTS: Taxol, cisplatin and 5-fluorouracil were in general more effective than adriamycin and mitomycin for GC cells, and the chemosensitivity to anticancer drugs was associated with tumor histological types and a worse tumor grade. Compared to normal gastric mucosa tissues, hTERT mRNA expression was significantly increased in GC (P<0.05), which was related with a worse differentiation and drug-resistance to 5-fluorouracil or adriamycin in GC. CONCLUSIONS: These data demonstrate for the first time that examinations of hTERT mRNA expression as an important factor could be used to select the chemotherapeutic drugs for GC patients. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1793217009875483.

Effects of taurocholic acid on immunoregulation in mice.

CONTEXT: Currently, there is a dramatically growing interest in Chinese traditional medicines, especially in the therapy of inflammatory diseases. Taurocholic acid (TCA), as a kind of natural bioactive substance of animal bile acid, has medicinal applications to treat a wide range of inflammatory diseases. OBJECTIVE: The study was designed to evaluate the effects of TCA on cytokine secretion, such as TNF-α and IL-1ß and on the ratio of CD4(+)/CD8(+), which is beneficial for understanding the mechanism of TCA on immunoregulation preliminarily, and also will benefit our further research. MATERIALS AND METHODS: The gene and protein expressions of TNF-α and IL-1ß were measured by real time RT-PCR and ELISA in serum, spleen and lymphocytes respectively. The ratio of CD4(+)/CD8(+) in peripheral blood and lymphocytes was measured by flow cytometry. RESULTS: Our present study has shown that lipopolysaccharide (LPS) and cyclosporin A (CsA) could increase or decrease the gene and protein expressions of TNF-α and IL-1ß respectively. TCA (0.25g/kg, 0.125g/kg) could recover the suppressed expressions of TNF-α and IL-1ß and increase the ratio of CD4(+)/CD8(+). In vitro, TCA (15µg/mL) could inhibit the increased production of TNF-α and IL-1ß; TCA (0.15µg/mL-15µg/mL) could inhibit the increased gene expressions of IL-1ß and TNF-α. TCA (0.15µg/mL) could recover the suppressed expressions of TNF-α and IL-1ß. CONCLUSION: The function of immunoregulation of TCA may be accomplished through modulating the gene and protein expressions of TNF-α and IL-1ß and elevating CD4(+)/CD8(+) T-cell ratio.

[Effect of taurochenodeoxycholic acid on immune function in mice].

OBJECTIVE: To observe the influence of Taurochenodeoxycholic Acid (TCDCA) on immun, function in mice. METHODS: T-Cell subgroups were determined by using Flow cytometry; The content of anti-body in serum was assayed by using Spectrophotometry; The phagocytosis of mononuclear phagocyte system was determined by using Carbon particle clearance test and anti-sheep blood cell hemolysin was determined by using Turbidimetric method. RESULTS: TCDCA signifeantly enhanced the percentage of CD and CD19+ lymphocytes and CD4+/CD8+ value in peripheral blood and the content of serum hemolysin and lysozymem in mice. Moreover, TCDCA markedly improved the phagocytosis functions of mononuclear phagocyte system and observably inhibited delayed type hypersensitivity. CONCLUSION: TCDCA can significantly enhance the immune function in mice.

[Studies on antitussive, antiasthmatic and expectorant action of chenodeoxycholine acid].

OBJECTIVE: In this paper, antitussive, antiasthmatic and expectorant action of chenodeoxycholine acid (CDCA) were studied. METHOD: The method of strong aqua ammoniae induced cough and sulfur dioxide induced cough, the method of tracheal volume and tracheal spiral line, and phenolsulfonphthalein excretion test. RESULTS: CDCA was able to prolong cough latent period and decrease cough rate significantly in mice resulted from strong aqua ammoniae and sulfur doxide, and inhibit contraction of whole-body or extracorpored tracheal smooth muscle in guinea pig resulted from histamine phosphate. Besides, CDCA can increase phenolsulfonphthalein excretion quantity of trachea in mice, singnificantly. CONCLUSION: CDCA has antitussive, antiasthmatic, expectorant actions.

[Studies on mechanism of antiasthmatic and anti-inflammatory actions of CDCA].

OBJECTIVE: To observe antiasthmatic and anti-inflammatory actions mechanisms of CDCA. METHOD: The content of NO was determined by method of nitroreductase chromatometry in serum and trachea tissue. The content of cAMP was analysed by method of competitive protein-binding assay. The content of PGE2 was determined by method of ultraviolet spectrophotometry. RESULT: CDCA significantly decreased the content of NO of serum and trachea tissue in mice. CDCA increased greatly the content of cAMP of trachea tissue in rats. CDCA significantly decreased the content of PGE2 of trachea and lung tissue in mice. CONCLUSION: Mechanisms of antiasthmatic and anti-inflammatory actions of CDCA are related to increasing the content of cAMP in trachea tissue and decreasing the constituent of NO and PGE2 in body.