New Bisabolane-Type Sesquiterpenoids from Curcuma longa and Their Anti-Atherosclerotic Activity.

To explore the sesquiterpenoids in Curcuma longa L. and their activity related to anti-atherosclerosis. The chemical compounds of the rhizomes of C. longa were separated and purified by multiple chromatography techniques. Their structures were established by a variety of spectroscopic experiments. The absolute configurations were determined by comparing experimental and calculated NMR chemical shifts and electronic circular dichroism (ECD) spectra. Their anti-inflammatory effects and inhibitory activity against macrophage-derived foam cell formation were evaluated by lipopolysaccharide (LPS) and oxidized low-density lipoprotein (ox-LDL)-injured RAW264.7 macrophages, respectively. This study resulted in the isolation of 10 bisabolane-type sesquiterpenoids (1-10) from C. longa, including two pairs of new epimers (curbisabolanones A-D, 1-4). Compound 4 significantly inhibited LPS-induced nitric oxide (NO), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and prostaglandin E2 (PGE2) production in RAW264.7 cells. Furthermore, compound 4 showed inhibitory activity against macrophage-derived foam cell formation, which was represented by markedly reducing ox-LDL-induced intracellular lipid accumulation as well as total cholesterol (TC), free cholesterol (FC), and cholesterol ester (CE) contents in RAW264.7 cells. These findings suggest that bisabolane-type sesquiterpenoids, one of the main types of components in C. longa, have the potential to alleviate the atherosclerosis process by preventing inflammation and inhibiting macrophage foaming.

Mesenchymal stem cell-derived exosomes and non-coding RNAs: Regulatory and therapeutic role in liver diseases.

Liver disease has become a major health problem worldwide due to its high morbidity and mortality. In recent years, a large body of literature has shown that mesenchymal stem cell-derived exosomes (MSC-Exo) are able to play similar physiological roles as mesenchymal stem cells (MSCs). More importantly, there is no immune rejection caused by transplanted cells and the risk of tumor formation, which has become a new strategy for the treatment of various liver diseases. Moreover, accumulating evidence suggests that non-coding RNAs (ncRNAs) are the main effectors by which they exert hepatoprotective effects. Therefore, by searching the databases of Web of Science, PubMed, ScienceDirect, Google Scholar and CNKI, this review comprehensively reviewed the therapeutic effects of MSC-Exo and ncRNAs in liver diseases, including liver injury, liver fibrosis, and hepatocellular carcinoma. According to the data, the therapeutic effects of MSC-Exo and ncRNAs on liver diseases are closely related to a variety of molecular mechanisms, including inhibition of inflammatory response, alleviation of liver oxidative stress, inhibition of apoptosis of hepatocytes and endothelial cells, promotion of angiogenesis, blocking the cell cycle of hepatocellular carcinoma, and inhibition of activation and proliferation of hepatic stellate cells. These important findings will provide a direction and basis for us to explore the potential of MSC-Exo and ncRNAs in the clinical treatment of liver diseases in the future.

Sesquiterpenoids from the Florets of Carthamus tinctorius (Safflower) and Their Anti-Atherosclerotic Activity.

(1) Background: The florets of Carthamus tinctorius L. are traditionally used as a blood-activating drug and can be used for the treatment of atherosclerosis, but no compounds with anti-atherosclerotic activity have been reported. (2) Methods: This study investigated the chemical compounds from the florets of C. tinctorius. Comprehensive spectroscopic techniques revealed their structures, and ECD calculations established their absolute configurations. Nile Red staining, Oil Red O staining, and cholesterol assessment were performed on these compounds and their aglycones for the inhibitory activity against the formation of foam cells induced by oxidized low-density lipoprotein (ox-LDL) in RAW264.7 macrophages. In addition, RAW264.7 macrophages were tested for their anti-inflammatory activity by measuring the inhibition of NO production caused by LPS. (3) Results: Five new sesquiterpenoids (1-5) isolated from the florets of C. tinctorius were identified as (-)-(1R,4S,9S,11R)-caryophyll-8(13)-en-14-ol-5-one (1), (+)-(1R,4R,9S,11R)-caryophyll-8(13)-en-14-ol-5-one (2), (-)-(3Z,1R,5S,8S,9S,11R)-5,8-epoxycaryophyll-3-en-14-O-ß-D-glucopyranoside (3), (+)-(1S,7R,10S)-guai-4-en-3-one-11-O-ß-D-fucopyranoside (4), and (-)-(2R,5R,10R)-vetispir-6-en-8-one-11-O-ß-D-fucopyranoside (5). All compounds except for compound 3 reduced the lipid content in ox-LDL-treated RAW264.7 cells. Compounds 3 and 4 and their aglycones were found to reduce the level of total cholesterol (TC) and free cholesterol (FC) in ox-LDL-treated RAW264.7 cells. However, no compounds showed anti-inflammatory activity. (4) Conclusion: Sesquiterpenoids from C. tinctorius help to decrease the content of lipids, TC and FC in RAW264.7 cells, but they cannot inhibit NO production, which implies that their anti-atherogenic effects do not involve the inhibition of inflammation.

RNA sequencing-based identification of microRNAs in the antler cartilage of Gansu red deer (Cervus elaphus kansuensis).

Background: The velvet antler is a complex mammalian bone organ with unique biological characteristics, such as regeneration. The rapid growth stage (RGS) is a special period in the regeneration process of velvet antler. Methods: To elucidate the functions of microRNAs (miRNAs) at the RGS of antler development in Gansu red deer (Cervus elaphus kansuensis), we used RNA sequencing (RNA-seq) to analyze miRNA expression profiles in cartilage tissues of deer antler tips at three different growth stages. Results: The RNA-seq results revealed 1,073 known and 204 novel miRNAs, including 1,207, 1,242, and 1,204 from 30-, 60-, and 90-d antler cartilage tissues, respectively. To identify key miRNAs controlling rapid antler growth, we predicted target genes of screened 25 differentially expressed miRNAs (DEMs) and specifically expressed miRNAs (SEMs) in 60 d and annotated their functions. The KEGG results revealed that target genes of 25 DEMs and 30 SEMs were highly classified in the "Metabolic pathways", "Pathways in cancer", "Proteoglycans in cancer" and "PI3K-Akt signaling pathway". In addition, a novel miRNA (CM008039.1_315920), highly enriched in "NF-kappa B signaling pathway", may need further study. Conclusions: The miRNAs identified in our study are potentially important in rapid antler growth. Our findings provide new insights to help elucidate the miRNA-mediated regulatory mechanisms involved during velvet antler development in C. elaphus kansuensis.

Integrative Analyses of Antler Cartilage Transcriptome and Proteome of Gansu Red Deer (Cervus elaphus kansuensis) at Different Growth Stages.

The velvet antler is a unique model for cancer and regeneration research due to its periodic regeneration and rapid growth. Antler growth is mainly triggered by the growth center located in its tip, which consists of velvet skin, mesenchyme and cartilage. Among them, cartilage accounts for most of the growth center. We performed an integrative analysis of the antler cartilage transcriptome and proteome at different antler growth stages. RNA-seq results revealed 24,778 unigenes, 19,243 known protein-coding genes, and 5535 new predicted genes. Of these, 2722 were detected with differential expression patterns among 30 d, 60 d, and 90 d libraries, and 488 differentially expressed genes (DEGs) were screened at 30 d vs. 60 d and 60 d vs. 90 d but not at 30 d vs. 90 d. Proteomic data identified 1361 known proteins and 179 predicted novel proteins. Comparative analyses showed 382 differentially expressed proteins (DEPs), of which 16 had differential expression levels at 30 d vs. 60 d and 60 d vs. 90 d but not at 30 d vs. 90 d. An integrated analysis conducted for DEGs and DEPs showed that gene13546 and its coding protein protein13546 annotated in the Wnt signaling pathway may possess important bio-logical functions in rapid antler growth. This study provides in-depth characterization of candidate genes and proteins, providing further insights into the molecular mechanisms controlling antler development.

Macrophage Polarization and Its Role in Liver Disease.

Macrophages are important immune cells in innate immunity, and have remarkable heterogeneity and polarization. Under pathological conditions, in addition to the resident macrophages, other macrophages are also recruited to the diseased tissues, and polarize to various phenotypes (mainly M1 and M2) under the stimulation of various factors in the microenvironment, thus playing different roles and functions. Liver diseases are hepatic pathological changes caused by a variety of pathogenic factors (viruses, alcohol, drugs, etc.), including acute liver injury, viral hepatitis, alcoholic liver disease, metabolic-associated fatty liver disease, liver fibrosis, and hepatocellular carcinoma. Recent studies have shown that macrophage polarization plays an important role in the initiation and development of liver diseases. However, because both macrophage polarization and the pathogenesis of liver diseases are complex, the role and mechanism of macrophage polarization in liver diseases need to be further clarified. Therefore, the origin of hepatic macrophages, and the phenotypes and mechanisms of macrophage polarization are reviewed first in this paper. It is found that macrophage polarization involves several molecular mechanisms, mainly including TLR4/NF-κB, JAK/STATs, TGF-ß/Smads, PPARγ, Notch, and miRNA signaling pathways. In addition, this paper also expounds the role and mechanism of macrophage polarization in various liver diseases, which aims to provide references for further research of macrophage polarization in liver diseases, contributing to the therapeutic strategy of ameliorating liver diseases by modulating macrophage polarization.