Keratoconus, historically viewed as a non-inflammatory disease, is an ectatic corneal disorder associated with progressive thinning of the corneal stroma. Recently, a few inflammatory mediators have been reported to be elevated in the tear fluid of keratoconus patients. Consequently, we investigated a wide range of inflammation regulating cytokines in the tears and sera of keratoconus and control subjects. Interleukin (IL)-1β, IL-4, IL-6, IL-10, IL-12, IL-13, IL-17, interferon (IFN)-γ, chemokine C-C motif ligand 5 (CCL5) and tumor necrosis factor (TNF)-α were tested in tear samples and sera of keratoconus and control individuals by multiplex immuno-bead assays. Selected cytokines were further tested by standard ELISA on pooled tear samples. All cytokines in the sera were generally low, with no significant changes between keratoconus and control subjects. However, in tear fluids, clear differences were detected between the two groups. These differences include increased IL-6, and decreased IL-12, TNF-α, IFN-γ, IL-4, IL-13 and CCL5 in keratoconus compared to control tear fluids. The decreases in IL-12, TNF-α and CCL5 were statistically significant, while the IL-13 decrease was statistically significant in the severe keratoconus group only. IL-17 could not be detected by multiplex immuno-bead assay, but showed an increase in keratoconus by conventional ELISA on a limited number of pooled tear samples. Our findings confirm increased IL-6, but dispute earlier reports of increased TNF-α, and suggest a cytokine imbalance in keratoconus disrupting corneal homeostasis. Moreover, an increase in IL-17 suggests tissue degenerative processes at work, contributing to the thinning and weakening of the corneal connective tissue in keratoconus.

Cardiovascular and metabolic diseases (CVMD) are the leading causes of death worldwide, underscoring the urgent necessity to develop new pharmacotherapies. Berberine (BBR) is an eminent component of traditional Chinese and Ayurvedic medicine for more than 2000 years. Recently, BBR has attracted much interest for its pharmacological actions in treating and/or managing CVMD. Recent discoveries of basic, translational and clinical studies have identified many novel molecular targets of BBR (such as AMPK, SIRT1, LDLR, PCSK9, and PTP1B) and provided novel evidences supporting the promising therapeutic potential of BBR to combat CVMD. Thus, this review provides a timely overview of the pharmacological properties and therapeutic application of BBR in CVMD, and underlines recent pharmacological advances which validate BBR as a promising lead drug against CVMD.

No abstract

Drug resistance, including adriamycin (ADR)-based therapeutic resistance, is a crucial cause of chemotherapy failure in breast cancer treatment. Acquired chemoresistance has been identified to be closely associated with the overexpression of P-glycoprotein (P-gp/ABCB1). Long non-coding RNA (lncRNA) growth arrest-specific 5 (GAS5) can be involved in carcinogenesis; however, its roles in ABCB1-mediated ADR resistance are poorly understood. In this study, we identified a panel of differentially expressed lncRNAs, mRNAs, and mi-croRNAs (miRNAs) in MCF-7 and MCF-7/ADR cell lines through RNA sequencing (RNA-seq) technologies. GAS5 level was downregulated whereas ABCB1 level was upregulated in the resistant breast cancer tissues and cells. Overexpression of GAS5 significantly enhanced the ADR sensitivity and apoptosis, and it inhibited the efflux function and expression of ABCB1 in vitro, while knockdown of GAS5 had the opposite effects. Further mechanism-related investigations indicated that GAS5 acted as an endogenous "sponge" by competing for miR-221-3p binding to regulate its target dickkopf 2 (DKK2), and then it inhibited the activation of the Wnt/b-catenin pathway. Functionally, GAS5 enhanced the anti-tumor effect of ADR in vivo. Collectively, our findings reveal that GAS5 exerted regulatory function in ADR resistance possibly through the miR-221-3p/DKK2 axis, providing a novel approach to develop promising therapeutic strategy for overcoming chemoresistance in breast cancer patients.

Cardiovascular and cerebrovascular diseases are the main cause of mortality worldwide, currently with less than optimum therapeutic options. Danhong injection (DHI) is a medicinal preparation based on two eminent Chinese herbal medicines, Salviae Miltiorrhizae (Dan Shen; family: Lamiaceae) and Flos Carthami (Hong Hua; family: Compositae/Asteraceae). DHI has been mainly used in the clinical therapy of cardiovascular (such as acute coronary syndrome and angina pectoris) and cerebrovascular diseases (such as stroke) in China for many years. The pharmacological properties of DHI include anti-inflammatory, anti-oxidant, anti-coagulatory, hypolipidemic, anti-apoptotic, vasodilatory, and angiogenesis-promoting actions. DHI offers a safe and effective therapeutic agent against cardiovascular and cerebrovascular diseases by modulating multiple disease-relevant signaling pathways and molecular targets. Herein, we provide a comprehensive review of the phytochemistry, therapeutic effects, molecular mechanisms, and adverse reactions of DHI in cardiovascular and cerebrovascular diseases. We also highlight the latest pharmacological advances and therapeutic potential of this promising herb-derived cardiovascular drug preparation.

Eight secondary metabolites, including three new azaphilones (chermesinones A-C, 1-3), three new p-terphenyls (6'-O-desmethylterphenyllin, 4; 3-hydroxy-6'-O-desmethylterphenyllin, 5; 3''-deoxy-6'-O-desmethylcandidusin B, 7), and two known p-terphenyls (6, 8), were isolated from the culture of the mangrove endophytic fungus Penicillium chermesinum (ZH4-E2). Their structures were established by spectroscopic analysis. The absolute configuration of 1 was determined by X-ray crystallography. Terphenyls 4, 5, and 6 exhibited strong inhibitory effects against α-glucosidase with IC50 values of 0.9, 4.9, and 2.5 μM, respectively. Terphenyls 7 and 8 showed inhibitory activity toward acetylcholinesterase with IC50 values of 7.8 and 5.2 μM.

No abstract

Cardiovascular disease is the main cause of death worldwide, but its pathogenesis is not yet clear. Hydrogen sulfide (H2S) is considered to be the third most important endogenous gasotransmitter in the organism after carbon monoxide and nitric oxide. It can be synthesized in mammalian tissues and can freely cross the cell membrane and exert many biological effects in various systems including cardiovascular system. More and more recent studies have supported the protective effects of endogenous H2S and exogenous H2S-releasing compounds (such as NaHS, Na2S, and GYY4137) in cardiovascular diseases, such as cardiac hypertrophy, heart failure, ischemia/reperfusion injury, and atherosclerosis. Here, we provided an up-to-date overview of the mechanistic actions of H2S as well as the therapeutic potential of various classes of H2S donors in treating cardiovascular diseases.