Objective: To evaluate the effect of pingyangmycin-albumin microspheres (PYM-AMS) on the modality of endothelial cells. Methods:In the in vitro study blood vessle endothelial cells of ECV 304 cell line were exposed to PYM-AMS(containing PYM at 150 ?g/ml),AMS and PYM(150 ?g/ml) for 24,48,72 and 96 h respectively. In the in vivo study,24 Japanese white rabbits were divided into 4 groups using randomized block design. PYM+9 g/L NaCl,PYM+soyabean oil, PYM-AMS+soyabean oil(PYM at 5 mg/ml) were injected into the central auricular arteries of the animals(0.26 ml/per ear), then these vessels were examined histologically 2, 7, 14, 21 days after injection respectively. The mophorlogy of the cells was observed by light microscope and electron microscope.Results:In vitro, a great part of cells were swollen and cell number decreased in PYM and PYM-AMS group. But there was no change in AMS group.In vivo, the endothelial cells had no significant changes in PYM+9 g/L NaCl group.In PYM+soyabean oil group, at the 2nd day, the endothelial cells were a little bit swollen. At the 7th day, some endothelial cells were dropped off. At the 21st day, a few of endothelial cells were proliferative. In PYM-AMS group, at the 2nd day, the endothelial cells were a little bit swollen and small vessels were embolized by PYM-AMS. At the 7th day, the endothelial cells were swollen. At the 14th day, the endothelial cells were proliferative and the wall of the central auricular artery had more layers. The lumen of the central artery became smaller, while the surface of PYM-AMS was absorbed. At the 21st day, the wall of the central auricular artery was proliferative and the artery became sclerostenosed. The PYM-AMS was obviously absorbed, while the wall of small vein was proliferative, too. Conclusion:PYM-AMS and PYM may injure blood vessel endothelial cells, the effect of PYM-AMS is more obvious than pingyangmycin.

0.05), except PYM-AMS of 1.130 mg/ml and PYM of 300 ?g/ml at 24 h.In the same group and at the same exposure time,higher dose of the corresponding agents showed higher growth inhibition ratio(P0.05).At the same doses 48 h exposure of PYM-AMS or PYM gave higher apoptosis rate than 24 h exposure(P

ve To investigate the effects of clinical relevant concentrations of midazolam on whole-cell N-type calcium currents of sympathetic ganglion neurons trying to assess the involvement of sympathetic ganglion in circulation depression produced by midazolam. Methods 7-10 d SD rats were decapitated and bilateral superior cervical ganglions were rapidly removed and kept in 4℃, oxygen saturated incubation solution. TTX 1?mol/L and nifedipine 10 ?mol/L were added to the solution to block the Na+ and L-type calcium currents. Midazolam was also added to the solution. The final concentration of midazolam were 0.1, 0.3, 3, 10, 50, 100?mol/L.The effects of different concentration of midazolam on the whole-cell N-type calcium channel currents were assessed by patch-clamp technique. Results When the holding potential (Vh) was - 80mV and stimulating votage(Vt) was between - 30mV and 10mV midazolam inhibited the whole-cell N-type calcium currents dose-dependently ( r = 0.964, P

On the basis of analyzing the transition and development trend of current medical and pharmaceutical mode,this article proposed that in the process of pharmacy talents training,not only biological,but also the construction of natural drugs knowledge should be stressed.In addition,the necessity of natural drugs knowledge construction as well as its practice and future blueprint in our university were illuminated intensively,in order to provide reference for the training of pharmacy talents in local colleges.

AIM:To explore the effect of the pretreatment of hypertonic saline(HTS) in hepatic ischemia reperfusion(I/R) injury.METHODS:The rats were divided into sham group(sham group),ischemia reperfusion group(IR group) and pretreatment of hypertonic saline group(HTS group).Partial hepatic ischemia reperfusion model was used.The rats were sacrificed at the time of 1 h,3 h,6 h,12 h and 24 h after reperfusion in each group,respectively.Blood samples were obtained to examine ALT.The expression of the CD11b/CD18(Mac-1) on the neutrophils was analyzed by flow cytometry.RT-PCR and Western blotting were used to examine the expression of intercellular adhesion molecule-1(ICAM-1) in livers and chromatometry was performed to detect the activity of myeloperoxidase(MPO) in livers.The morphology of hepatocytes and the structure of sinusoid were observed by histological examinations.RESULTS:① HTS pretreatment decreased the level of ALT at the time points of 3 h,6 h and 12 h after reperfusion(P

Aim The effects of diazepam on the whole cell sodium currents in rat sympathetic ganglion neurons were studied to investigate the mechanisms by diazepam mediates hypotension. Methods Whole cell patch clamp recordings were performed on enzymatically isolated rat superior cervical sympathetic ganglion neurons. Results Diazepam dose dependently blocked the whole cell sodium currents. Under a V t of 0 mV and a V h of 80 mV 0.3 ?mol?L -1 diazepam reduced sodium peak currents by 14.76 %(P

AIM: To study the interactions of propofol and midazolam on the whole cell sodium channel currents in rat sympathetic ganglion neurons. METHODS: Whole cell patch clamp recordings were made from enzymatically isolated rat (7- 10 d ) superior cervical sympathetic ganglion neurons. Isobolographic analysis was applied to evaluate the potency of combinations of propofol and midazolam on Na + channel currents. RESULTS: Under V h= 80 mV and V t= 0 mV . Propofol and midazolam dose dependently blocked Na + currents with a mean drug concentration required to produce 50% current inhibition (IC 50 ): 33.12 ?mol?L -1 and 18.35 ?mol?L -1 ; clinically relevant concentrations of propofol and midazolam reduced Na + peak currents by 27.66 % (P

Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by abnormal lipid deposition in the liver and its mechanism is closely related to insulin resistance, lipid metabolism disorders, oxidative stress, and abnormalities of the gut-liver axis. Currently, there is no effective treatment for this disease. Silent information regulator 2 (SIRT2) is a nicotinamide adenine dinucleotide (NAD⁺)-dependent deacetylase which performs various pathophysiological functions by interacting with different substrates. For example, it is involved in improving metabolic homeostasis, alleviating liver inflammation, promoting liver regeneration, and delaying the progression of MASLD. In this paper, we present a review of the mechanism of action of SIRT2 in MASLD to analyze the potential value of SIRT2 as a therapeutic target in MASLD.

AIM: To investigate the effects of alanyl - glutamine ( Ala -Gln) on expression of iNOS and TNF- α in injured intestinal mucosa induced by oral tacrolimus (FK506). METHODS: Twenty -four BALB/c mice were randomized to receive orally 0.2 mL of normal saline solution ( group Ⅰ ), 0.2 mL of FK506 in a dose of 0.1 mg/kg ( group Ⅱ ) or 1.0 mg/kg (group Ⅲ), and orally high -dose FK506 (0.2 mL, 1.0 mg/kg) plus intraperitoneal injection of Ala -Gln (0.5 g/kg )(group Ⅳ ),respectively. Damages of intestinal mucosa were determined by pathological examination.Intestinal mucosal permeability was analysed by FITC - dextran fluorescence assay. Expression of iNOS and TNF - α in intestine was detected by RT - PCR and Western blotting. RESULTS: Severe damage on the villi and increased intestinal permeability were observed in high - dose FK506 treated mice according to scanning electron microscopy and FITC - dextran flux respectively. The erosion and increased intestinal permeability were significantly alleviated by Ala - Gln treatment. Transcription of iNOS mRNA and TNF - α mRNA, which was up - regulated in high - dose FK506 treated group,was also markedly down- regulated in mice combined with Ala- Gln- treatment. A significantly increased expression of iNOS and TNF - α protein was found in the high - dose FK506 treated mice, while small amounts of these proteins were identified in the Ala - Gln - treated group. CONCLUSION: FK506 could induce a significant impairment of intestinal mucosa morphologically, which might be associated with up - regulated expression of iNOS and TNF - α in small intestinal mucosa. Subsequently, the intestinal permeability is increased. Ala - Gln has a strong protective effect on FK506 - induced intestinal barrier dysfunction, probably relates to the down - regulation of iNOS and TNF - α expression.

Objective To evaluate the role of β-arrestin-1 in penehyclidine hydrochloride (PHC)-induced inhibition of lipopolysaccharide (LPS)-caused increase in pulmonary microvascular permeability in human pulmonary microvascular endothelial cells (PMVECs).Methods Human PMVECs were seeded in 6-well plates (2 ml/well) or in culture flasks (4 ml/flask) at the density of 1 × 105 cells/ml and divided into 5 groups (n=15 each) using a random number table:empty plasmid transfection group (group C),LPS plus empty plasmid transfection group (LPS group),PHC plus LPS plus empty plasmid transfection group (P+LPS group),LPS plus β-arrestin-1 short hairpin RNA (shRNA) transfection group (LPS+shRNA group) and PHC plus LPS plus β-arrestin-1 shRNA transfection group (P+LPS+shRNA group).In LPS and LPS+shRNA groups,the cells were transfected with empty plasmid 1.5 μg or with plasmid containing 15 nmol/L β-arrestin-1 shRNA,LPS with the final concentration of 0.1 μg/ml was added at 24 h of incubation,and the cells were then incubated for 1 h.In P+LPS and P+LPS+shRNA groups,the cells were transfected with empty plasmid 1.5 μg or with plasmid containing 15 nmol/L β-arrestin-1 shRNA,PHC with the final concentration of 2 μg/ml was added at 24 h of incubation,LPS with the final concentration of 0.1 μg/ml was added at 1 h of incubation,and the cells were then incubated for 1 h.The cell permeability was measured using Transwell chambers.The expression of heat shock protein (HSP27) was detected by immunofluorescence.The expression of β-arrestin-1,p38 mitogen-activated protein kinase (p38MAPK) and phosphorylated p38MAPK (p-p38MAPK) was detected by Western blot.The ratio of pp38MAPK/p38MAPK was calculated.Results Compared with group C,the cell permeability was significantly increased,the expression of HSP27 was up-regulated,p-p38MAPK/p38MAPK ratio was increased,and the expression of β-arrestin-1 was down-regulated in LPS,LPS + shRNA and P + LPS + shRNA groups (P＜0.05),and no significant change was found in the parameters mentioned above in group P+LPS (P＞ 0.05).Compared with group LPS,the cell permeability was significantly decreased,the expression of HSP27 was down-regulated,p-p38MAPK/p38MAPK ratio was decreased,and the expression of β-arrestin1 was up-regulated in group P +LPS,and p-p38MAPK/p38MAPK ratio was significantly increased (P＜0.05),and no significant change was found in the other parameters in group P+LPS+shRNA (P＞0.05).Compared with group P+LPS,the cell permeability was significantly increased,the expression of HSP27 was up-regulated,p-p38MAPK/p38MAPK ratio was increased,and the expression of β-arrestin-1 was down-regulated in group P+LPS+shRNA (P＜0.05).Conclusion The mechanism by which PHC inhibits LPS-induced increase in pulmonary microvascular permeability is totally related to β-arrestin-1 in human PMVECs.