Curcumin- and Cyclopamine-Loaded Liposomes to Enhance Therapeutic Efficacy Against Hepatic Fibrosis.

BACKGROUND AND PURPOSE: Hepatic fibrosis is a public health problem characterized by activation of hepatic stellate cells (HSCs), which triggers excessive production of extracellular matrix (ECM). Inhibition of HSC activation may be an effective treatment. Since various pathways control HSC activation, a combination of drugs with different mechanisms may be more effective than monotherapy. METHODS: Here, we prepared liposomes loaded with curcumin and cyclopamine to inhibit HSC activation. We systematically analyzed the physicochemical characteristics of liposomes loaded with the two drugs, as well as their effects on HSC proliferation, activation and collagen production on gene, protein and cellular levels. RESULTS: The prepared liposomes helped solubilize both drugs, contributing to their uptake by cells. Liposomes loaded with both drugs inhibited cell proliferation, migration and invasion, as well as induced more apoptosis and perturbed the cell cycle more than the free combination of both drugs in solution or liposomes loaded with either drug alone. Liposomes loaded with both drugs strongly suppressed HSC activation and collagen secretion. CONCLUSION: Our results suggest that liposome encapsulation can increase the uptake of curcumin and cyclopamine as well as the synergism between them in anti-fibrosis. This approach shows potential for treating hepatic fibrosis.

Study on the diagnosis of gout with xanthine and hypoxanthine.

BACKGROUND: Hyperuricemia is the only biochemical index in the classification of acute gouty arthritis in American Rheumatism Association 1977 and the main basis of clinical diagnosis for most doctors. However, nearly half of the time gout occurs without hyperuricemia, especially in an acute attack，which leads to an urgent need to find a new substitute diadynamic criteria of gout. Xanthine and hypoxanthine, as precursors of uric acid, have been reported to be high in gout patients with hyperuricemia and presumed to be gout biomarkers. OBJECTIVES: To further explore the possibility of xanthine and hypoxanthine to be gout biomarkers as substitutes for uric acid. METHODS: A reversed-phase HPLC-UV method was employed for simultaneous quantitative detection of uric acid (UA), xanthine (X), and hypoxanthine (HX) in gout patients' (with and without hyperuricemia) and healthy persons' serum. RESULTS: The xanthine and hypoxanthine concentrations in gout patients with hyperuricemia and without hyperuricemia are higher than in healthy persons with a P < 0.001. CONCLUSIONS: This study supplements previous researches by confirming that xanthine and hypoxanthine are significantly elevated in gout patients' serum especially in patients' with normouricemia, which supported xanthine and hypoxanthine may have clinical application for the diagnosis of gout.

Chaiqin Chengqi decoction inhibits inflammatory mediators and attenuates acute pancreatitis through deactivation of janus kinase/signal transducer and activator of transcription signaling pathway.

OBJECTIVE: To investigate the effect of Chaiqin Chengqi decoction (CQCQD) on acute pancreatitis (AP) by janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway in vitro and in vivo. METHODS: AP was induced by caerulein both in AR42J cells and in mice. AR42J cells were divided into five groups: the control group, the AP group, the CQCQD group, JAK/STAT signaling pathway inhibitor AG490 group, and the CQCQD and AG490 group. After induction, cellular supernatant of five groups were collected for measuring the concentrations of inflammatory cytokine amylase, interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), interleukin 1ß (IL-1ß), nuclear factor κB (NF-κB) by enzyme-linked immunosorbent assay and the expression of JAK-2, STAT-3 signaling transduction proteins by Western blot, respectively. Experiments in mice were performed similar to that of in AR42J cells. RESULTS: Treatment of AR42J cells with CQCQD reduced the pancreatic injury and negatively regulated the activities of amylase, as well as inhibited expression of several inflammatory cytokines such as IL-6, TNF-α, IL-1ß, NF-κB. Administration of CQCQD significantly inhibited JAK-2 activation and down-regulated phosphorylation of downstream substrate STAT-3 the same as AG490, resulting in inhibition of inflammatory mediators and amelioration of pancreatitis. CONCLUSION: The results suggested that CQCQD exerted anti-inflammatory effects on AP via reducing expression and phosphorylation of JAK and STAT.

Antioxidant and immunomodulatory activities of a polysaccharide from Flammulina velutipes.

OBJECTIVE: To evaluate the antioxidant and immunomodulatory activities of a unique polysaccharide from the medicinal fungus Flammulina velutipes in vitro. METHODS: Using water extraction and alcohol precipitation, crude polysaccharides were obtained. After purification by DEAE-cellulose 52 ion exchange chromatography and Sephacryl S-300 HR gel filtration chromatography, High performance liquid chromatography equipped with evaporative light-scattering detector, Infrared radiation and Nuclear magnetic resonance were used to evaluate the structure of the polysaccharide. Its immunomodulatory activity was measured by examining the production of nitric oxide (NO) and cytokine secretion, and via lymphocyte proliferation experiments. Its effects on the scavenging activities of hydroxyl radical, superoxide anion and reducing power were also measured. RESULTS: A water-soluble polysaccharide, Flammulina velutipes polysaccharide I-A (FVP I-A), was obtained with a molecular mass of 8.14 x 10(4) Da determined by high performance gel permeation chromatography. An in vitro antioxidant assay indicated that FVP I-A could scavenge hydroxyl radical, superoxide anion and possessed reducing power and could largely promote NO production and augment the interleukin-1ß, interleukin-6, and tumor necrosis factor-α secretion by RAW264.7 macrophages (P < 0.05). Moreover, FVP I-A could promote lymphocyte proliferation (P < 0.05), and synergistically enhance the augmentation of the proliferation of mouse lymphocytes by concanavalin A and lipopolysaccharides (P < 0.01, P < 0.05). CONCLUSION: The FVP I-A obtained from Flammulina velutipes possessed antioxidant activity and could enhance non-specific and specific immune responses in vitro.