Celastrol inhibits lung cancer growth by triggering histone acetylation and acting synergically with HDAC inhibitors.

Alterations in histone modification have been linked to cancer development and progression. Celastrol, a Chinese herbal compound, shows potent anti-tumor effects through multiple signaling pathways. However, the involvement of histone modifications in this process has not yet been illustrated. In this study, barcode sequencing of a eukaryotic genome-wide deletion library revealed that histone modifications, especially histone acetylation associated with the NuA4 histone acetyltransferase complex, were involved in the anti-proliferation actions of celastrol. The essential roles of histone modification were verified by celastrol sensitivity tests in cells lacking specific genes, such as genes encoding the subunits of the NuA4 and Swr1 complex. The combination of celastrol and histone deacetylase inhibitors (HDACi), rather than the combination of celastrol and histone acetyltransferase inhibitors, synergistically suppressed cancer cell proliferation. In addition to upregulating H4K16 acetylation (H4K16ac), celastrol regulates H3K4 tri-methylation and H3S10 phosphorylation. Celastrol treatment significantly enhanced the suppressive effects of HDACi on lung cancer cell allografts in mice, with significant H4K16ac upregulation, indicating that a combination of celastrol and HDACi is a potential novel therapeutic approach for patients with lung cancer.

Traditional Patchouli essential oil modulates the host's immune responses and gut microbiota and exhibits potent anti-cancer effects in ApcMin /+ mice.

Patchouli Essential Oil (PEO) has been used as a scent for various healing purposes since the ancient Egyptian period. The primary source of the oil is Pogostemon cablin (PC), a medicinal plant for treating gastrointestinal symptoms. However, the pharmacological function has not been addressed. Here, we report the cancer prevention and gut microbiota (GM) modulating property of PEO and its derivatives patchouli alcohol (PA) and pogostone (PO) in the ApcMin /+ colorectal cancer mice model. We found that PEO, PA, and PO significantly reduced the tumor burden. At the same time, it strengthened the epithelial barrier, evidenced by substantially increasing the number of the goblet and Paneth cells and upregulation of tight junction and adhesion molecules. In addition, PEO, PA, and PO shifted M1 to M2 macrophage phenotypes and remodeled the inflammatory milieu of ApcMin /+ mice. We also found suppression of CD4+CD25+ and stimulation CD4+ CD8+ cells in the spleen, blood, mesenteric lymph nodes (MLNs), and Peyer's patches (PPs) of the treated mice. The composition of the gut microbiome of the drug-treated mice was distinct from the control mice. The drugs stimulated the short-chain fatty acids (SCFAs)-producers and the key SCFA-sensing receptors (GPR41, GPR43, and GPR109a). The activation of SCFAs/GPSs also triggered the alterations of PPAR-γ, PYY, and HSDCs signaling mediators in the treated mice. Our work showed that PEO and its derivatives exert potent anti-cancer effects by modulating gut microbiota and improving the intestinal microenvironment of the ApcMmin /+ mice.

Bifidobacterium animalis: the missing link for the cancer-preventive effect of Gynostemma pentaphyllum.

Colorectal cancer (CRC) ranks the third most common cancer type in both men and women. Besides the known genetic and epigenetic changes in the gut epithelial cells, we now know that disturbed gut microbes could also contribute to the onset and progression of CRC. Hence, keeping a balanced gut microbiota (GM) has become a novel pursue in the medical field, particularly in the area of gastrointestinal disorders. Gynostemma pentaphyllum (Gp) is a dietary herbal medicine. In our previous study, Gp saponins (GpS) displayed prebiotic and cancer-preventive properties through the modulation of GM in ApcMin/+ mice. However, the specific group(s) of GM links to the health effects of GpS remains unknown. To track down the missing link, we first investigated and found that inoculation with fecal materials from GpS-treated ApcMin/+ mice effectively reduces polyps in ApcMin/+ mice. From the same source of the fecal sample, we successfully isolated 16 bacterial species. Out of the 16 bacteria, Bifidobacterium animalis stands out as the responder to the GpS-growth stimulus. Biochemical and RNAseq analysis demonstrated that GpS enhanced expressions of a wide range of genes encoding biogenesis and metabolic pathways in B. animalis culture. Moreover, we found that colonization of B. animalis markedly reduces the polyp burden in ApcMin/+ mice. These findings reveal a mutualistic interaction between the prebiotic and a probiotic to achieve anticancer and cancer-preventive activities. Our result, for the first time, unveils the anticancer function of B. animalis and extend the probiotic horizon of B. animalis.

Effect of various Danshen injections on patients with coronary heart disease after percutaneous coronary intervention: A protocol for a systematic review and network meta-analysis.

BACKGROUND: Patients with coronary heart disease (CHD) who undergo percutaneous coronary intervention (PCI) have a certain risk of vascular complications, including coronary restenosis and thrombosis. Many recent randomized controlled trials have reported that Danshen injection (DSI) combined with conventional Western medicine can significantly reduce the occurrence of major cardiovascular adverse events in patients with CHD after PCI. However, there are many types of DSIs, and no study has yet compared each type. Therefore, we propose a study protocol for the systematic evaluation of the efficacy of various DSIs in the treatment of CHD after PCI. METHODS: We will search the following electronic databases for randomized controlled trials evaluating the effect of DSI in patients with CHD after PCI: PubMed, Embase, Web of Science, Cochrane Library, Scopus, Ovid Evidence-Based Medicine Reviews, China National Knowledge Infrastructure, and Chinese Biomedicine Literature Database. Each database will be searched from inception to April 2018. The entire process will include study selection, data extraction, risk of bias assessment, pairwise meta-analyses, and network meta-analyses. RESULTS: This proposed study will compare the efficacy of different DSIs in the treatment of patients with CHD after PCI. The outcomes will include major cardiovascular adverse events and left ventricular ejection fraction. CONCLUSION: This proposed systematic review will evaluate the different advantages of various types of DSIs in the treatment of patients with CHD after PCI. REGISTRATION: PROSPERO (registration number: CRD42018092705).

[Fast analysis of common fatty acids in edible vegetable oils by ultra-performance convergence chromatography-mass spectrometry].

A fast analytical method for five common fatty acids in six edible vegetable oils was developed by ultra-performance convergence chromatography-mass spectrometry (UPC2-MS). The five fatty acids are palmitic acid, stearic acid, oleic acid, linoleic acid and linolenic acid. Their contents in the corn oil, sunflower oil, soybean oil, tea oil, rapeseed oil and peanut oil were compared. The chromatographic separation was performed on an ACQUITY UPC2 BEH 2-EP column (100 mm x 2.1 mm, 1.7 µm) using the mobile phases of carbon dioxide and methanol/acetonitrile (1:1, v/v) with gradient elution. The separated compounds were detected by negative electrospray ionization ESF-MS. The results showed that the reasonable linearities were achieved for all the analytes over the range of 0.5-100 mg/L with the correlation coefficients (R2) of 0.9985-0.9998. The limits of quantification (S/N ≥ 10) of the five fatty acids were 0.15-0.50 mg/L. The recoveries of the five fatty acids at three spiked levels were in the range of 89.61%-108.50% with relative standard deviations of 0.69%-3.01%. The developed method showed high performance, good resolution and fast analysis for the underivatized fatty acids. It has been successfully used to detect the five fatty acids from corn oil, sunflower oil, soybean oil, tea oil rapeseed oil and peanut oil.