Largazole Inhibits Ocular Angiogenesis by Modulating the Expression of VEGFR2 and p21.

Ocular angiogenic diseases, characterized by abnormal blood vessel formation in the eye, are the leading cause of blindness. Although Anti-VEGF therapy is the first-line treatment in the market, a substantial number of patients are refractory to it or may develop resistance over time. As uncontrolled proliferation of vascular endothelial cells is one of the characteristic features of pathological neovascularization, we aimed to investigate the role of the class I histone deacetylase (HDAC) inhibitor Largazole, a cyclodepsipeptide from a marine cyanobacterium, in ocular angiogenesis. Our study showed that Largazole strongly inhibits retinal vascular endothelial cell viability, proliferation, and the ability to form tube-like structures. Largazole strongly inhibits the vessel outgrowth from choroidal explants in choroid sprouting assay while it does not affect the quiescent choroidal vasculature. Largazole also inhibits vessel outgrowth from metatarsal bones in metatarsal sprouting assay without affecting pericytes coverage. We further demonstrated a cooperative effect between Largazole and an approved anti-VEGF drug, Alflibercept. Mechanistically, Largazole strongly inhibits the expression of VEGFR2 and leads to an increased expression of cell cycle inhibitor, p21. Taken together, our study provides compelling evidence on the anti-angiogenic role of Largazole that exerts its function through mediating different signaling pathways.

Cytotoxic trichothecene macrolides from the endophyte fungus Myrothecium roridum.

A new cytotoxic roridin-type trichothecene macrolide named epiroridin acid (1) and two known compounds epiroridin E (2) and mytoxin B (3) were isolated from the liquid culture of Myrothecium roridum A553, which was isolated from the medicinal plant Pogostemon cablin. The structure of the new macrolide (1) was elucidated by extensive spectroscopic measurements (UV, IR, MS, and 1D and 2D NMR) analyses. All isolated compounds (1-3) were evaluated for their cytotoxic activities against SF-268, MCF-7, NCI-H460, and HepG-2 tumor cell lines. The new compound (1) exhibited well cytotoxicity against the four selected tumor cell lines.

[Protective effect of total glycosides of Ranunculus japonicus on myocardial ischemic-reperfusion injury in isolated rat hearts].

OBJECTIVES: To study the protective effect of total glycosides of Ranunculus japonicus (TGRJ) on myocardial ischemic-reperfusion injury in isolated rat hearts. METHODS: The SD rats were randomly divided into normal control group, ischemia-reperfusion group, and TGRJ in 0.05, 0.10 and 0.20 mg/mL groups. The ischemia-reperfusion injury model was built using Langendroff isolated rats hearts perfusion system. The indexes of heart function such as heart rate (HR), left ventricular systolic pressure (LVSP), left ventricular systolic pressure maximum rate of rise (+ dp/dt(max)), left ventricular diastolic pressure maximum rate of descent (-dp/dt(max)) and coronary flow (CF) before ischemia and later at 1, 5, 10, 20, 30 and 40 min after reperfusion were recorded. The activity of Lactate dehydrogenase (LDH) and creatine kinase (CK) at 20 and 40 min after reperfusion were determined. The myocardial tissues were stained with Triphenyltetrazolium chloride (TTC) and the percentage of myocardial infarction area was calculated. RESULTS: HR, LVDP, +dp/dt(max) and CF of the I/R group were significantly decreased after reperfusion, LDH and CK levels were increased and the area of myocardial infraction was 58.78%. TGRJ had improving effect on all above indexes. CONCLUSION: TGRJ has protective effet on the myo- cardial ischemic-reperfusion injury.

[Effect of TGRJ on blood press, NO and Ang II in renal hypertensive rats].

OBJECTIVE: To study the effect of total glycosides of Ranunculus japoniucus (TGRJ) on blood pressure, nitric oxide (NO) calcium and angiotensin II (Ang II) in renal hypertensive rats (RHR). METHODS: 1) RHR were established by two kidney one clip (2K1C) and drugs were given by intragastric administration for 5 week, the blood pressure were measured at the end of 5 week,detected the concentration of NO in the serum and Ang II in the blood plasma,heart and kidney tissue. 2) Used a new generations of Ca2+ fluorescent probe (Fluo-3/AM) to mark calcium in vascular smooth muscle cells. Observed the fluorescence imaging by inverted fluorescence microscope and measured the fluorescence intensity of calcium by fluorescence spectrophotometer in vascular smooth muscle cells. RESULTS: 1) The high, medium doses of TGRJ could decrease blood pressure of RHR (P<0.05), TGRJ could significantly increase the concentration of NO in the serum (P<0.01), but it showed no significant effect on the concentration of Ang II (P>0.05); 2) The Ang II could significantly promote the calcium ions in extracellular inner flow. The different doses of TGRJ could reduce the calcium ions in cells which were mediated by Ang II. CONCLUSION: TGRJ could decrease blood pressure in RHR. the mechanism might be related to increasing the rats' NO level and reducing the calcium ions level in cells which are increased by Ang II.

[Detecting the information of cucumber in greenhouse for picking based on NIR image].

For the cucumber harvesting robot, the identification of target information is one of important tasks in the automation of fruit-picking. In order to implement spatial fruit localization and quality discrimination in greenhouse, this paper presented a machine vision algorithm for the recognition and detection of cucumber fruits based on near-infrared spectral imaging. By comparing the spectral reflectance of cucumber plant (fruit, leaf and stem) from visible to infrared region (325-1 075 nm) measured by ASD FieldSpec Pro VNIR spectrometer, a monospectral near-infrared image at the 850 nm sensitive wavelength was captured to cope with the similar-color segmentation problem in complex environment. Then, a method of fruit extraction was developed on the basis of the following steps. Firstly, from the gray level histogram it was observed that the pixels of fruit distributed on the right are lesser than that of background, so "P parameter threshold method" was used to image segmentation. Subsequently, divided local image was partitioned into several sub-blocks by the application of adaptive template mining, which was feasible for processing the fruit with long-column feature. Finally, noises including parts of stem and leaf were eliminated using estimation condition of barycentre position and area size, proved by relative experiment In addition, the region for robotic grasping was established by gray variation between fruit-handle and fruit pedicel, as the quality feature was extracted with morphological characteristics of the centre-line length and the fruit flexure degree. A detecting experiment was carried out on 30 images with cucumber fruits and 10 images with no fruits, which were taken in a changing greenhouse environment. The results indicate that the accuracy rate of the recognition was 83.3% and 100%, while the success rate of effectively acquiring the grasping region was 83.3%, which can meet the demand of robotic fruit-harvesting.