1. Hydrogen sulphide (H₂S), one of three signalling gasotransmitters, plays an important role in oxidative stress and apoptosis. However, the effects of H₂S on oxidative stress-induced apoptosis in focal cerebral ischaemic injury in rats have not been clarified. 2. In the present study, sodium hydrosulphide (NaHS) was used as the H₂S donor. Eighty-four Sprague-Dawley rats were randomly divided into six groups: sham, sham + low-dose (2.8 mg/kg) NaHS, sham + high-dose (11.2 mg/kg) NaHS, infarct, infarct + low-dose NaHS and infarct + high-dose NaHS. The focal cerebral ischaemic model was created by cranially inserting a nylon thread with a rounded tip into an internal carotid artery. Rats were killed 21 h after administration of NaHS. 3. In the infarct + low-dose NaHS compared with infarct group, infarct volume was significantly decreased and injury to the mitochondria in nerve cells was mitigated. Furthermore, significant increases were seen in mitochondrial superoxide dismutase and glutathione peroxidase activity and neuronal bcl-2 protein levels, whereas mitochondrial malondialdehyde content and neuronal bax and caspase 3 protein levels were significantly decreased, in the infarct + low-dose NaHS compared with infarct group. The effects seen in the infarct group were significantly aggravated in the infarct + high-dose NaHS group. 4. The findings of the present study provide novel evidence for the dual effects of H₂S on focal cerebral ischaemic injury via modulation of oxidative stress-induced apoptosis.

Three series of novel artemisinin-guanidine hybrids 4a-4f, 8a-8h and 9a-9h have been facilely synthesized via four-component reaction (aza-Wittig reaction) and evaluated for their anti-tumor activities against A549, HT-29 and MDA-MB-231 cell lines in vitro. All of the tested compounds showed enhanced anti-tumor activities with IC(50) values ranging from 0.02 µM to 12.0 µM as compared to DHA (dihydroartemisinin). Among them, artemisinin derived dimers, compounds 9b (IC(50)  = 0.05 µM), 9d (IC(50)  = 0.06 µM) and 9f (IC(50)  = 0.02 µM) were found to be most active against HT29 cells.

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Abstract.Hydrogen sulfide (H 2 S) is a signaling gasotransmitter, involved in various physiological and pathological processes. H 2 S-donating drugs have been tested to conjugate the beneficial effects of H 2 S with other pharmaceutical properties. It has been shown that the endogenous cystathionine-γ-lyase (CSE)/H 2 S pathway participates in myocardial ischemia injury in isolated hearts in rats. The present study aimed to investigate the cytoprotective action of H 2 S against acute myocardial ischemia injury in rats. Isolated rat hearts were perfused and subjected to ischemic conditions for 4 h. The hearts were assigned to five groups: Sham, model, infarct plus low-dose (5 µmol/l) NaHS, infarct plus middle-dose (10 µmol/l) NaHS and infarct plus high-dose (20 µmol/l) NaHS. The administration of NaHS enhanced the activity of CSE, increased the content of H 2 S and reduced infarct volumes following myocardial ischemia injury. Furthermore, the administration of NaHS attenuated the injury to organelles (including the mitochondria, nucleus and myofilaments) by reducing lactate dehydrogenase activity, decreasing the level of mitochondrial malondialdehyde and increasing the activities of superoxide dismutase and glutathione peroxidase in the ischemic myocardial mitochondria. These protective effects of H 2 S against myocardial ischemia injury appeared to be mediated by its antioxidant activities and the preservation of mitochondrial function.

Despite cancer chemotherapy has entered a new era of molecularly targeted therapeutics and some forms of cancer have been successfully treated by modern therapies, the successful treatment of cancer remains a significant challenge in the future because chemotherapy is limited by the drug resistance and adverse side effects.1) In order to develop more effective and reliable anticancer agents that circumvent these limitations, the search for novel anti-tumor agents has turned to natural products, in particular plants used in traditional folk medicines. 2)In recent years, artemisinin and its derivatives have been widely studied for their anticancer activities. Some of them showed excellent anti-tumor activity toward different cancer cell lines in vitro. [3][4][5][6][7][8][9] Also, several studies demonstrated that artemisinin analogues were effective to many drug-and radiation-resistant cancer cell lines due to their multiple mechanisms. 10,11) The main mode likely involves a similar metalinduced free-radical formation leading to induce apoptosis in cancer cells and inhibit the tumor angiogenesis. [12][13][14][15][16] Recently, considerable attention has been focused on chalcones, which are a class of privileged structures that are easily prepared and have a wide range of biological properties, [17][18][19][20][21] which makes them an attractive pharmacophoric scaffold. An area of particular interest is their potential as antitumor agents, for which several modes of action have been proposed. The key mechanism is the inhibition of tubulin polymerization, while also including the inhibition of angiogenesis and the induction of apoptosis. [22][23][24] Chalcones and artemisinin analogues represent two classes of natural products, whose antitumor effects appear to be consistent via different molecular mechanisms. As the application of hybrid strategy to synthesize artemisinin analogues are continuously emerging, 9,25) it is reasonable to combine their structure analogues to form a single molecular framework with a linker, which would allow us to find more potent anti-tumor agents, in which these 'merge' pharmacophore may be addressing the active site of different targets and offering the possibility to overcome drug resistance. Intrigued by these observations, we designed and synthesized two new series of novel artemisinin derivatives by replacement of oxygen at C-10 with nitrogen, in which the substituted chalcone group is bonded to the artemisinin nucleus through an oxyacetyl linkage.Chemistry The synthetic routes of compounds are outlined in Chart 1. Separable diastereomeric mixture of 10b-azidodihydroartemisinin (2) and 10a-azidodihydroartemisinin (3) were obtained by treating 1 with trimethylsilyl chloride, sodium azide and sodium iodide at room temperature for 28 h, according to ref 6. The a and b isomers appeared as two distinct spots on TLC and were separated by column chromatography, with b-isomers as the major products. The reduction of azido compounds (2, 3) with Staudinger reaction afforded the correspondin...

Lymph node metastasis is the primary site of metastasis for patients with gallbladder cancer (GBC). Vascular endothelial growth factor-C (VEGF-C) has been implicated in the control of lymphangiogenesis and lymph node metastasis in various malignant tumors. However, the function of circulating VEGF-C is unclear and it is often difficult to evaluate lymph node metastasis and provide a prognosis for GBC. In the present study, ELISA was used to measure the preoperative serum VEGF-C (sVEGF-C) levels of 51 patients with GBC, 15 patients with chronic cholecystitis and 10 healthy volunteers. The results revealed a significantly increased sVEGF-C level in patients with GBC compared with the healthy donors, however no statistically significant difference was identified between patients with GBC and chronic cholecystitis. sVEGF-C levels were associated with lymph node metastasis in GBC and presented a positive correlation with VEGF-C expression and lymphatic vessel density (LVD) in patients with GBC. The mean survival time with high sVEGF-C was significantly reduced compared with low sVEGF-C. A similar result was also observed for VEGF-C expression and LVD. In summary, sVEGF-C levels may predict lymph node metastasis and the prognosis of patients with GBC.

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