Mechanisms underlying the antidiarrheal,antispasmodic and bronchodilator activities of Fumaria parviflora and involvement of tissue and species specificity

Ethnopharmacological relevance: In the Greco-Arab (Unani) traditional medicine, Fumaria parviflora Linn. is widely used in hypreractive gut and respiratory disorders including diarrhea, abdominal cramps, indigestion and asthma but scientific studies to provide rational for these medicinal uses are sparse. This study was therefore undertaken to provide ethnopharmacological basis for its medicinal use in diarrhea, abdominal cramps and asthma.     

Progranulin promotes colorectal cancer proliferation and angiogenesis through TNFR2/Akt and ERK signaling pathways

Progranulin (PGRN) has been shown to be involved in the process of inflammation, wound healing, and cartilage development; and its role in the progression of breast and ovarian cancer is also well established. However, the expression status of PGRN in colorectal cancers (CRCs) and its molecular mechanisms responsible for tumorigenesis have not been addressed so far. Herein, we demonstrated that PGRN was highly expressed and had clinical relevance with CRCs since its overexpression was associated with advanced stages of CRCs, poorer patients’ prognosis, and increased expression of proliferation and angiogenesis markers. PGRN up-regulation significantly promoted the expression of Ki67 and vascular endothelial growth factor A (VEGF-A) as well as the growth rate in CRC cell lines, while PGRN down-regulation had the opposite effects. Strikingly, PGRN derived from CRCs could directly induce proliferation, migration, tubule formation, as well as VEGF-A expression in human umbilical vein endothelial cells (HUVECs). Furthermore, we provided mechanistic evidences that the regulation of Ki67 and VEGF-A expression by PGRN was mediated by tumor necrosis factor receptor 2 (TNFR2)/Akt and the ERK signaling pathways in both CRC cells and HUVECs. Taken together, these findings suggested that PGRN could promote proliferation and angiogenesis through TNFR2/Akt and ERK signaling pathways in CRCs, providing the new insight into the mechanism of PGRN in tumor proliferation and angiogenesis.     

临床研究协调员(CRC)行业指南(试行)

随着中国药物临床研究事业的发展, 临床研究协调员(CRC)作为新兴的行业, 扮演着越来越重要的角色。目前国内尚无统一的行业管理标准与指南, 严重影响了CRC行业的健康发展。基于此, 中关村玖泰药物临床试验技术创新联盟/中国药物临床试验机构联盟起草制定了《临床研究协调员行业管理指南》, 从CRC职业基本要求、培训、等级评估、工作要求、监督管理等方面规范了行业行为。     

Gut and airways relaxant effects of Carum roxburghianum

Ethnopharmacological relevance

Carum roxburghianum is traditionally used in hyperactive gastrointestinal and respiratory disorders. The present study was carried out to investigate the possible gut and airways relaxant potential of Carum roxburghianum to rationalize its folk uses.

Materials and methods

Crude extract of Carum roxburghianum (Cr.Cr) was studied in in vivo and in vitro techniques.

Results

Cr.Cr exhibited protective effect against castor oil-induced diarrhea in mice at 100–1000 mg/kg. In rabbit jejunum preparations, Cr.Cr (0.03–3.0 mg/mL) caused relaxation of spontaneous and K⁺ (80 mM)-induced contractions at similar concentrations, like papaverine. Pretreatment of tissues with Cr.Cr (0.1–1.0 mg/mL) shifted Ca⁺⁺ concentration–response curves (CRCs) to right, like verapamil. Cr.Cr (0.03 and 0.1 mg/mL) caused leftward shift of isoprenaline-induced inhibitory CRCs, similar to papaverine. In isolated guinea-pig ileum, Cr.Cr (0.01 and 0.03 mg/mL) produced rightward parallel shift of acetylcholine-curves, like atropine. Cr.Cr (1.0–30 mg/kg) caused suppression of carbachol (CCh, 100 μg/kg)-induced increase in inspiratory pressure of anaesthetized rats. In guinea-pig trachea, Cr.Cr (0.03–1.0 mg/mL) relaxed CCh and high K⁺-induced contractions, shifted isoprenaline-induced inhibitory CRCs to left at 0.1 and 0.3 mg/mL and CCh-curves parallel to right (0.01 and 0.03 mg/mL). Cr.Cr did not cause any mortality of mice up to 10 g/kg dose.

Conclusion

These results indicate that Carum roxburghianum possess combination of antidiarrheal, antispasmodic and bronchodilatory effects, which provides pharmacological basis to its traditional use in the disorders of gut and airways hyperactivity, like diarrhea, colic and asthma.     

Increased number of arginase 1-positive cells in the stroma of carcinomas compared to precursor lesions and nonneoplastic tissues

Arginase 1 (Arg1) is involved in dampening the response of antitumor T lymphocytes. Arg1 expression has been reported in a variety of cancer cell lines and tumor-associated myeloid-derived cells. However, its examination in situ in tumor microenvironment is poorly investigated. We examined the Arg1-positive cells in tumor microenvironment of gastric carcinomas (GCs), colorectal carcinomas (CRCs) and prostate carcinomas (PCs), and analyzed their clinicopathological significance. Immunohistochemical staining for Arg1 was done in 60 GCs, 38 gastric adenomas, 40 CRCs, 10 colonic adenomas, 36 PCs, and 15 benign prostatic hyperplasia (BPH). Arg1 expression was predominantly localized in tumor microenvironment and the stroma of nonneoplastic tissues. Cells with Arg1 expression were mostly leukocytes, morphologically resembling polymorphonuclear neutrophils, and showed CD15 expression. Arg1 expression was focally expressed in cancer cells of 6 PCs, but not in those of GCs and CRCs. Arg1-positive cells were significantly more infiltrated in tumors than adenomas and nonneoplastic tissues, such as BPH, intestinal metaplasia and adjacent tissues. There were no significant findings between them and clinicopathological parameters, except for the relationship to gender and tumor differentiation in CRCs. These findings suggest that Arg1-positive cells in tumor microenvironment is involved in the occurrence of GCs, CRCs, and PCs. More expansive studies are necessary to better elucidate their clinicopathological significance in carcinomas.     

SPARC and DNA methylation: Possible diagnostic and therapeutic implications in gastrointestinal cancers

DNA methylation is a major contributor to epigenetic alterations and as such is a potential biomarker and therapeutic target in gastrointestinal malignancies. DNA methylation is commonly observed in several Gastrointestinal (GI) malignancies including pancreatic and colorectal cancer. Methylation results in decreased expression of tumor suppressor genes. Secreted protein acidic and rich in cysteine (SPARC) is a tumor suppressor gene that can be functionally inactivated through methylation. SPARC is commonly dysregulated in GI malignancies. Inhibition of DNA methylation can reverse the silencing of SPARC. In the present review, we will discuss recent advances in our understanding of the features of DNA methylation that pertain to SPARC, focusing on their functional and clinical relevance in GI carcinogenesis.