Penicacids E-G, three new mycophenolic acid derivatives from the marine-derived fungus Penicillium parvum HDN17-478.

Three new mycophenolic acid derivatives, penicacids E-G (1-3), together with three known analogues, mycophenolic acid (4), 4'-hydroxy-mycophenolic acid (5) and mycophenolic methyl ester (6), were isolated from a marine-derived fungus Penicillium parvum HDN17-478 from a South China Sea marine sediment sample. The structures of compounds 1-3 were elucidated by HRMS, NMR, and Mosher's method. Among them, compounds 1 and 2 were the first examples of mycophenolic acid analogs with a double bond at C-3'/C-4' position. The cytotoxicity of 1-6 was evaluated against the HCT-116, BEL-7402, MGC-803, SH-SY5Y, HO-8910 and HL-60 cell lines, and compounds 4 and 6 showed potent cytotoxicity with IC50 values ranging from 1.69 to 12.98 µmol·L-1.

Study on the mechanism of anti-MIRI action of total flavones of Fructus Chorspondiatis by PET/CT imaging.

BACKGROUND: To investigate anti myocardial ischemia/reperfusion injury (MIRI) action of total flavones of Fructus Chorspondiatis (TFFC) in rats by 13N-ammonia micro PET/CT imaging, etc. METHODS: Male Sprague-Dawley rats were randomly divided into 6 groups. Micro PET/CT imaging was performed before and after modeling to calculate the volume (VOI) and SUVmean of myocardial ischemic area. The oxidative stress index [(superoxide dismutase (SOD), malondialdehyde (MDA)] and the marker enzymes [creatine kinase (CK), lactate dehydrogenase (LDH)] of myocardial injury were detected. The pathological changes of myocardial were observed via HE staining. A MIRI model of rat cardiomyocytes in vitro was established, the damage and apoptosis of myocardial cells in each group were observed, and the apoptosis rate of cardiomyocytes was detected. RESULTS: The imaging viscosities of the imaging agents were observed at 24 and 48 h in each group. The VOI of 24 h imaging was (6.33±2.02), (6.01±1.56) and (3.32±0.86) mm3, respectively. The VOI of 48 h imaging was (3.31±1.33), (2.61±1.01) and (1.32±0.58) mm3. The 72 h imaging medium and high dose group recovered, while the low dose group still saw sparseness with (1.26±0.68) mm3 VOI. The ischemic (SUVmean) gradually increased with time. Metabolism gradually recovered (F=121.82, 450.82, 435.75, P<0.05). The three doses of TFFC can eliminate free radicals and reduce the damage of myocardial injury. Amongst them, the high-dose group had a better effect on SOD, and the middle-dose group had a better effect on MDA and LDH. The low-dose group affected CK, and a significant difference was observed compared with the control group (P<0.05). After administration, the morphology of myocardial cells in each dose group was improved to some extent. Nuclear pyknosis, rupture, the apoptosis rate, etc. were significantly reduced, the number of cells increased. The high dose group showed the most obvious improvement. CONCLUSIONS: The PET/CT imaging method can detect non-invasive, in vivo and dynamic MIRI, and can accurately evaluate the protective effect of traditional Mongolian medicine TFFC on MIRI. The Anti-MIRI of TFFC can scavenge free radicals, reduce oxidative stress damage, inhibit apoptosis, affect the activity of related enzymes.

New metabolites from a Mariana Trench-derived actinomycete Nocardiopsis sp. HDN 17-237.

One new ß,γ-butenoate derivative phenylbutenote (1), and one new α-pyrone nocapyrone T (2) were isolated from the deep-sea derived actinomycete Nocardiopsis sp. HDN 17-237. Their structures were elucidated by extensive HRMS, IR and NMR analyses. Among them, compound 1 is the first microbial natural products bearing a rare ß,γ-butenoate moiety, and compound 2 is the first α-pyrone isolated from strain of Mariana Trench. Compounds 1 and 2 were tested for antioxidant and antibacterial activities, while none of them showed significant activity.

Effects of sterigmatocystin on esophageal epithelium and experimental reflux esophagitis in rats.

Patients with reflux esophagitis experience an increased incidence of esophageal cancer. In China, this may be the result of contamination of the food supply by Aspergillus fungi, which is known to harbor sterigmatocystin, a carcinogenic mycotoxin. To delineate the potential link between sterigmatocystin and esophageal cancer, an experimental model of reflux esophagitis was developed in rats that had undergone a cardiectomy and partial pylorus ligation. The rats were treated with sterigmatocystin or saline, and esophageal squamous cell hyperplasia was assessed based on the pathological evaluation. The expression of proliferating cell nuclear antigen (PCNA), transporter associated with antigen processing 1 (TAP1) and low molecular weight protein 2 (LMP2) was determined by immunohistochemistry. Intraperitoneal administration of sterigmatocystin promoted the proliferation of squamous epithelium. In addition, it also increased the expression of PCNA in esophageal epithelial cells in rats with reflux esophagitis and was correlated with the increased severity of epithelial hyperplasia. The expression levels of TAP1 and LMP2, which are located in the cytoplasm of esophageal epithelial cells, were reduced in rats with reflux esophagitis, and sterigmatocystin exposure further decreased the expression. Thus, the downregulation of TAP1 and LMP2 proteins by sterigmatocystin may directly affect tumor immunity by allowing transformed cells to escape the host immune surveillance, thereby promoting esophageal cancer.

Ultrasonically activated scalpel versus monopolar electrocautery shovel in laparoscopic total mesorectal excision for rectal cancer.

AIM: To investigate the feasibility and safety of monopolar electrocautery shovel (ES) in laparoscopic total mesorectal excision (TME) with anal sphincter preservation for rectal cancer in order to reduce the cost of the laparoscopic operation, and to compare ES with the ultrasonically activated scalpel (US). METHODS: Forty patients with rectal cancer, who underwent laparoscopic TME with anal sphincter preservation from June 2005 to June 2007, were randomly divided into ultrasonic scalpel group and monopolar ES group, prospectively. White blood cells (WBC) were measured before and after operation, operative time, blood loss, pelvic volume of drainage, time of anal exhaust, visual analogue scales (VAS) and surgery-related complications were recorded. RESULTS: All the operations were successful; no one was converted to open procedure. No significant differences were observed in terms of preoperative and postoperative d 1 and d 3 WBC counts (P=0.493, P=0.375, P=0.559), operation time (P=0.235), blood loss (P=0.296), anal exhaust time (P=0.431), pelvic drainage volume and VAS in postoperative d 1 (P=0.431, P=0.426) and d 3 (P=0.844, P=0.617) between ES group and US group. The occurrence of surgery-related complications such as anastomotic leakage and wound infection was the same in the two groups. CONCLUSION: ES is a safe and feasible tool as same as US used in laparoscopic TME with anal sphincter preservation for rectal cancer on the basis of the skillful laparoscopic technique and the complete understanding of laparoscopic pelvic anatomy. Application of ES can not only reduce the operation costs but also benefit the popularization of laparoscopic operation for rectal cancer patients.