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Movement and phagocytosis characterize the fundamental actions of macrophages. Although it is known that the free fatty acid receptor GPR120 is expressed in macrophages and regulates cytokine expression to exert anti-inflammatory activities, the effects of GPR120 activation on the motility and phagocytosis of macrophages are not clear. In this study, mouse alveolar macrophages (AM) were stimulated with the GPR120 agonist TUG-891, and the changes in cell motility, intracellular Ca2+ concentration ([Ca2+]i), and the ability of phagocytosis were measured. Mouse AM in controls exhibited active movement in vitro, and TUG-891 significantly restrained AM movement. Meanwhile, TUG-891 stimulated a quick increase in [Ca2+]i in AM, which was blocked separately by the Gq protein inhibitor YM-254890, the phospholipase C (PLC) inhibitor U73122, or depletion of endoplasmic reticulum (ER) Ca2+ store by thapsigargin. The inhibition of AM movement by TUG-891 was eliminated by YM-254890, U73122, thapsigargin, and chelation of cytosolic Ca2+ by BAPTA. Moreover, TUG-891 inhibited AM phagocytosis of fluorescent microspheres, which was also blocked by YM-254890, U73122, thapsigargin, and BAPTA. In conclusion, GPR120 activation in mouse AM increases [Ca2+]i but inhibits the motility and phagocytosis via Gq protein/PLC-mediated Ca2+ release from ER Ca2+ store. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effects of ancient Chinese medical formula Xiayuxue Decoction (下瘀血汤, XYXD) on activation of hepatic stellate cells (HSCs) and defenestration of sinusoidal endothelial cells (SECs) in CCl-induced fibrotic liver of mice. Methods: High performance liquid chromatography was used to identify the main components of XYXD and control the quality of extraction. C57BL/6 mice were induced liver fibrosis by CCl exposure and administered with XYXD for 6 weeks simultaneously. Liver tissue was investigated by hematoxylin-eosin and Sirius-red staining. Sinusoidal fenestrations were observed by scanning electronic microscopy and fluorescent immunohistochemistry of PECAM-1 (CD31). Whole liver lysates were detected of α-smooth muscle actin (α-SMA) and type-I collagen by Western blot. Primary rat HSCs-T6 cells were analyzed by detecting α-SMA, F-actin, DNA fragmentation through confocal microscopy, Western blot, terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) assay and cellomics arrayscan, respectively. Results: Amygdalin and emodin in XYXD were identified. XYXD (993 mg/kg) inhibited Sirius red positive area up to 70.1% ( P<0.01), as well as protein levels of α-SMA and type-I collagen by 42.0% and 18.5% ( P<0.05) respectively. In vitro, XYXD (12.5 μg/mL, 50 μg/mL) suppressed the activation of HSCs and reversed the myofibroblastic HSCs into quiescent, demonstrated as inhibition of fluorescent F-actin by 32.3% and 46.6% ( P<0.05). Besides, XYXD induced the apoptosis of HSC-T6 cells by 20.0% ( P<0.05) and 49.5% ( P<0.01), evidenced by enhanced TUNEL positivity. Moreover, ultrastructural observation suggested XYXD inhibited defenestration of SECs, which was confirmed by 31.1% reduction of protein level of CD31 ( P<0.05). Conclusions: XYXD inhibited both HSCs activation and SECs defenestration which accompany chronic liver injuries. These data may help to understand the underlying mechanisms of XYXD for prevetion of chronic liver diseases. [ABSTRACT FROM AUTHOR]

Although hepatitis B virus (HBV)-related cirrhosis and hepatocellular carcinoma (HCC) cause a sever health problem worldwide, the underlying mechanisms are still elusive. This study aimed to investigate the responses of different cell types isolated from HBV transgenic mice. A cross-sectional set of hepatocytes and oval cells were obtained from HBV transgenic and control mice. Flow cytometry, immunohistochemistry and microarray were applied to investigate the cell biology of the hepatocytes and oval cells. Our results showed that HBV induced the proliferation of both cell oval cells and hepatocytes, and induced cell death of HBV hepatocytes while had minimal effects on oval cells. Further molecular and pathways analysis identified some genes and signaling pathways may be responsible for the different responses between oval cells and hepatocytes. In addition, analyses of selectively ten genes by IHC staining in human samples were consistent with microarray data. In summary, HBV transgenic mice is a useful model for studying the biological behaviors of oval cells affected by HBV and HBV-cirrhosis. Also, our results help better understand the mechanisms of HBV induced cirrhosis, and provide novel progenitor markers or prognostic/therapeutic markers. [ABSTRACT FROM AUTHOR]

Three undescribed sesquiterpenes, designed as pichinenoid A-C (1 – 3), along with nine known ones (4 – 12) were isolated from the stems and leaves of Picrasma chinensis. The new isolates including their absolute configurations were elucidated based on extensive spectroscopic methods, single crystal X-ray diffraction, and electronic circular dichroism (ECD) experiments, as well as comparison with literature data. Structurally, compounds 1 and 2 are descending sesquiterpenes, while pichinenoid C (3) is a rare sesquiterpene bearing a 2-methylenebut-3-enoic acid moiety at the C-6 side chain. All the isolated compounds were tested for their neuroprotective effects against the H 2 O 2 -induced damage on human neuroblastoma SH-SY5Y cells, and most of them showed moderate neuroprotective activity. Especially, compounds 1 , 3 – 5 , and 7 showed a potent neuroprotective effect at 25 or 50 μM. Moreover, the neuroprotective effects of compounds 1 and 4 were tested on a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) mouse model. Results of western blot and immunofluorescence indicated that compound 4 significantly counteract the toxicity of MPTP, and reversed the expression of tyrosine hydroxylase (TH) in substantia nigra (SN) and striatum (ST) of the mouse brain. Interestingly, western blot data suggested compound 4 also enhanced B-cell lymphoma-2 (Bcl-2) and heme oxygenase 1 (HO-1) expressions in the brain tissues from MPTP damaged mouse. [Display omitted] [ABSTRACT FROM AUTHOR]

Traditional Chinese Medicine (TCM) has many obvious advantages in the treatment of chronic conditions such as urinary tract infection (UTI). Dongbai-Tonglin-Fang (DBTL), a Chinese herbal formula, has been used for the treatment of UTI for more than 40 years with proven efficacy. However, its mechanism of action is still unknown. The purpose of this study is to evaluate the therapeutic efficacy of DBTL and its mechanism of action in a rat UTI model. E. coli solution induced UTI rat model was used to evaluate the therapeutic effect of DBTL on UTI. Biochemical indicators related to UTI were measured. The kidney tissue was stained with hematoxylin-eosin (HE) to observe pathological changes whilst the ear swelling, feet swelling, hot plate and body torsion tests were used to estimate the anti-inflammatory and analgesic effects of DBTL. After treatment with different doses of DBTL (1, 2, 4 g/kg), a decrease in weight of the kidney in the UTI rat model was observed. The contents of white blood cell, nitrite, urinary albumin, ketone body, bilirubin and occult blood in the urine were also reduced whilst an increase in the pH of urine was observed. HE staining showed that the pathological changes in the kidney tissue were alleviated. At the same time, ear swelling assay showed that the weight and the degree of swelling of the ear of the mice in DBTL groups were decreased remarkably. DBTL also reduced the degree of feet swelling of the rats caused by the adjuvant. Furthermore, with the DBTL treatment, the latency period of foot licking induced by thermal stimulation was increased while the number of twists was lessened. These results show that DBTL has an excellent therapeutic effect on UTI rats accompanying with anti-inflammation and analgesia. The data presented here lays the foundations for further investigations in the treatment of UTI. Image 1 [ABSTRACT FROM AUTHOR]