Soybean isoflavones alleviate cerebral ischemia/reperfusion injury in rats by inhibiting ferroptosis and inflammatory cascade reaction / 南方医科大学学报

OBJECTIVE@#To explore the mechanism that mediates the effect of soybean isoflavones (SI) against cerebral ischemia/reperfusion (I/R) injury in light of the regulation of regional cerebral blood flow (rCBF), ferroptosis, inflammatory response and blood-brain barrier (BBB) permeability.@*METHODS@#A total of 120 male SD rats were equally randomized into sham-operated group (Sham group), cerebral I/R injury group and SI pretreatment group (SI group). Focal cerebral I/R injury was induced in the latter two groups using a modified monofilament occlusion technique, and the intraoperative changes of real-time cerebral cortex blood flow were monitored using a laser Doppler flowmeter (LDF). The postoperative changes of cerebral pathological morphology and the ultrastructure of the neurons and the BBB were observed with optical and transmission electron microscopy. The neurological deficits of the rats was assessed, and the severities of cerebral infarction, brain edema and BBB disruption were quantified. The contents of Fe2+, GSH, MDA and MPO in the ischemic penumbra were determined with spectrophotometric tests. Serum levels of TNF-α and IL-1βwere analyzed using ELISA, and the expressions of GPX4, MMP-9 and occludin around the lesion were detected with Western blotting and immunohistochemistry.@*RESULTS@#The rCBF was sharply reduced in the rats in I/R group and SI group after successful insertion of the monofilament. Compared with those in Sham group, the rats in I/R group showed significantly increased neurological deficit scores, cerebral infarction volume, brain water content and Evans blue permeability (P < 0.01), decreased Fe2+ level, increased MDA level, decreased GSH content and GPX4 expression (P < 0.01), increased MPO content and serum levels of TNF-α and IL-1β (P < 0.01), increased MMP-9 expression and lowered occludin expression (P < 0.01). All these changes were significantly ameliorated in rats pretreated with IS prior to I/R injury (P < 0.05 or 0.01).@*CONCLUSION@#SI preconditioning reduces cerebral I/R injury in rats possibly by improving rCBF, inhibiting ferroptosis and inflammatory response and protecting the BBB.

A new amide compound from Onchidium verruculatum / 中草药

Objective: To study the chemical composition of the marine characteristic resource, Onchidium verruculatum from Hainan Island. Methods: Compound was separated and purified by silica gel and semi-preparative HPLC, detected by TLC, and identified by NMR and MS data. Compound 1 was evaluated for cytotoxic activity against four kinds of human tumor cell lines HepG-2, BEL-7042, A549, and MCF-7. Results: A new amide compound, N-(2-hydroxy-4-methoxy-5-methylphenyl)formamide (1), was isolated from mucus and muscle tissue of O. verruculatum. The results showed that compound 1 has moderate toxic activity against A549 and BEL-7402 cell lines, with IC50 value of 11.5 μg/mL and 19.4 μg/mL. Conclusion: Compound 1 is a new amide compound named onchumamide with moderate toxic activity on human tumor cells.

Effect of CDC73 gene mutation on clinical characteristics of sporadic children/adolescent-onset primarg hyperparathyroidism / 基础医学与临床

Objective To summarize the characteristics and molecular genetics of sporadic children /adolescent-onset primary hyperparathyroidism PHPT patients and analyze the difference of characteristics between patients with and without CDC73 gene mutations .Methods Germline mutation analyses of MEN1, CDC73, RET, CDKN1B, and CaSR genes were performed in 22 sporadic children/adolescent-onset PHPT patients .Their clinical data were retrospectively analyzed.Results Four patients were found to carry CDC 73 mutations with the mutation rate of 18%(4/22).Patients with CDC73 gene mutationshad higher rates of parathyroid carcinoma and atypical adenomas than those without ,and the recurrence rate postoperatively was as high as 50%.Conclusions Genetic mutation testing is recommended in spo-radic children/adolescent-onset PHPT patients, especially the CDC73 gene.