Leonurine-Repressed miR-18a-5p/SOCS5/JAK2/STAT3 Axis Activity Disrupts CML malignancy.

Leonurine, an active natural alkaloid compound isolated from Herba leonuri, has been reported to exhibit promising anticancer activity in solid tumors. The aim of this study was to explore whether leonurine is able to inhibit chronic myeloid leukemia (CML) malignancy. Here, we found that leonurine dose dependently inhibited the proliferation, migration, colony formation and promoted apoptosis of CML cells. Furthermore, leonurine markedly reduced CML xenograft growth in vivo. Mechanically, leonurine upregulated SOCS5 expression, thus leading JAK2/STAT3 signaling suppression. Silencing of SOCS5 by its siRNA abrogated the effect of leonurine on CML cells, demonstrating that SOCS5 mediates the anti-leukemia effect of leonurine. Notably, we observed that miR-18a-5p was remarkably increased in CML cells. Treating CML cells with leonurine significantly decreased miR-18a-5p expression. Moreover, we found miR-18a-5p repressed SOCS5 by directly targeting its 3'-UTR. miR-18a-5p downregulation induced by leonurine reduced the biological activity of CML cells by relieving miR-18a-5p repression of SOCS5 expression. Taken together, leonurine exerts significant anti-leukemia efficacy in CML by regulating miR-18a-5p/SOCS5/JAK2/STAT3 axis.

Iodosobenzene-Mediated Three-Component Selenofunctionalization of Olefins.

A three-component reaction of olefin, diselenide and water, alcohols, phenol, carboxylic acid, or amine by a commercially available hypervalent iodine(III) reagent, PhIO, was developed. This method provides access to a wide range of vicinally functionalized selenoderivatives under ambient conditions with mostly excellent yields and high diastereoselectivity. The developed reaction displays high levels of functional group compatibility and is suitable for the late-stage functionalization of styrene-functionalized biomolecules. Preliminary investigations on the mechanism of the reaction are also presented.

[Clinical study of iron metabolism indicators in ineffective hematopoiesis of myelodysplastic syndrome].

This study was purposed to investigate the iron metabolism changes and their clinical significance in myelodysplastic syndrome (MDS). Thirty eight transfusion independent MDS patients and 49 controls (21 AA patients, 28 normal volunteers) were enrolled in this study. The iron metabolism indicators including serum iron protein (SF), serum iron (SI), transferrin protein (Tf), total iron binding capacity (TIBC), transferrin saturation (TS), soluble transferrin receptor (sTfR) were detected, the intracellular and extracellular iron distribution were observed under microscope, the chromosome karyotype was analysis by FISH. The results showed that the serum SF, SI and TS levels in MDS group were lower than those in AA group, the serum SF value was higher than that in normal control group. There was no statistical difference between the SI, TS levels as compared with normal control group. The SI, TS levels showed a positive correlation with SF level(r = 0.281, P = 0.007; r = 0.338, P = 0.001, respectively). The serum TIBC in MDS group was no statistically significant difference from that in the control group. The Tf level in MDS group was higher than that in AA and normal control groups, and Tf level between later 2 groups did not show statistical difference. The proportion of sideroblasts in MDS group (57.19 ± 19.11%)was higher than that in AA group (35.00 ± 20.67%). The extracellular iron (+ + +- + + + +) (24%)was lower than that in AA group (33%), and bone marrow particle dyeable iron displayed mainly cocci-like distribution under microscope in patients with increased extracellular iron (+ + +- + + + +), while small need or massive distribution was observed in AA group.In addition, the abnormal chromosome karyotype was found in 15 out of 19 MDS cases (79%). There was no difference in iron metabolism indicators between the high-risk group and the low-risk group of MDS divided according to the International Prognostic Scoring System (WPSS). It is concluded that the iron loading in transfusion-independent patients obviously increases, displaying the enhancement of SF, Tf, intra-and extra-cellular iron, but lower than those in AA patients. It suggests that the abnormality exists in process of use, storage and discharge of iron in MDS patients.

Inhibitory effects of prostaglandin E1 on activation of hepatic stellate cells in rabbits with schistosomiasis.

BACKGROUND: Liver fibrosis is the result of an imbalance between synthesis and degradation of extracellular matrix proteins of the liver. At the cellular and molecular levels, this progressive process is mainly characterized by activation of hepatic stellate cells (HSCs). Schistosoma japonica is one of the most prevalent causes of liver fibrosis in China. It is characterized by hepatocyte damage, inflammation, and chronic parasite egg-induced granuloma formation leading to fibrosis. This study aimed to investigate the inhibitory effects of prostaglandin E1 (PGE1) on activation of HSCs and the alteration of type I and III collagen in rabbits with schistosomiasis. The study may promote the clinical application of praziquantel and PGE1 as a combined therapy to reverse hepatic fibrosis caused by schistosomiasis. METHODS: Rabbits were percutaneously infected with cercaria of S. japonicum. Seven rabbits were subjected to intravenous injections of PGE1 (2.5 mug/kg daily) from days 60 to 120 after infection. The ultrastructural changes in activated HSCs were observed under transmission electron microscopy. The expression of alpha-smooth muscle actin (alpha-SMA) was detected by immunohistochemistry. Fibril-forming collagens were detected by picrosirius staining. RESULTS: Activation of HSCs was a characteristic alteration in schistosome-induced hepatic fibrosis. The expression of contraction-related alpha-SMA and the content of collagens were increased. Exogenous PGE1 markedly inhibited the activation of HSCs and reduced the expression of alpha-SMA around the hepatic sinusoids (P<0.01). The contents of type I and III collagens were significantly attenuated. The ratio of staining area to the whole field (10X3.3) under a polarized light microscope in the untreated and treated groups was 37.25+/-9.71 vs. 13.38+/-4.24 (P<0.01) and 9.66+/-3.52 vs. 6.23+/-1.81 (P<0.05), respectively. CONCLUSIONS: Activation of HSCs may play a key role in the progress of schistosome-induced hepatic fibrosis. PGE1 effectively protects rabbit liver from fibrosis, at least in part by inhibiting the activation of HSCs.

[Morphology of lymph vessels in human gastric carcinoma tissues and its association with cancer metastasis].

OBJECTIVE: To investigate the morphology of the lymph vessels in human gastric carcinoma tissues and the relationship to cancer metastasis. METHODS: Morphological changes of the lymph vessels and capillaries in 32 cases of gastric carcinoma tissues and adjacent tissue of the tumor. RESULTS: Numerous lymph vessels and capillaries were seen with opened lumen in the adjacent tissues of the tumor, and fasciculated lymph capillaries were most frequent in gastric carcinoma. The maximal lumen area, perimeter and diameter of lymph vessels and capillaries in gastric carcinoma and the adjacent tissues were significantly different between metastatic group and non-metastatic group (P<0.05). CONCLUSIONS: Dilation of lymph vessels and capillaries due to interstitial edema of the adjacent tissues of gastric carcinoma facilitates tumor metastasis, and lymph metastasis of carcinoma cells occurs through mature lymph capillaries in the adjacent tissues.