OBJECTIVES: To study the mechanism mediating the protective effect of asiaticoside (AS) against myocardial ischemia-reperfusion injury (MIRI) in rats. METHODS: Fifty SD rats were randomized into sham-operated group, MIRI model group and AS treatment group. AS treatment was administered at low, moderate and high doses by daily gavage for 2 weeks before MIRI modeling (n=10). Serum levels of lactate dehydrogenase (LDH), creatine kinase isoenzyme (CK-MB), interleukin-18 (IL-18) and IL-1β, the volume of myocardial infarction and ischemia, and myocardial pathologies of the rats were determined or observed. The protein expression levels of NLRP3, ASC, caspase-1, GSDMD, GSDMD-N, IL-1β and IL-18 in the myocardial tissues were detected using Western blotting. The changes in the expression levels of these proteins were also detected in H9C2 cells with AS pretreatment prior to hypoxia-reoxygenation (H/R) injury. RESULTS: The rats models of MIRI exhibited significant myocardial infarction and ischemia with increased serum levels of LDH and CK-MB and myocardial expressions of NLRP3, ASC, caspase-1, GSDMD, GSDMD-N, IL-1β and IL-18. AS pretreatment effectively reduced myocardial infarction volume in the rat models and significantly reduced serum LDH and CK-MB levels and the protein levels in the myocardial tissue in a dose-dependent manner. In the H9C2 cell model of H/R injury, AS pretreatment significantly suppressed the elevation of the protein expressions of NLRP3, ASC, caspase-1, GSDMD, GSDMD-N, IL-1β and IL-18. Molecular docking studies showed that AS had a strong binding affinity with NLRP3. CONCLUSIONS Asiaticoside can alleviate MIRI in rats possibly by inhibiting NLRP3 inflammasome-mediated pyroptosis.
Animals ; Myocardial Reperfusion Injury/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Pyroptosis/drug effects* ; Rats, Sprague-Dawley ; Rats ; Inflammasomes/metabolism* ; Triterpenes/pharmacology* ; Interleukin-18/metabolism* ; Male ; Interleukin-1beta/metabolism* ; Caspase 1/metabolism*

The rapid screening of bioactive constituents within traditional Chinese medicine (TCM) presents a significant challenge to researchers. Prevailing strategies for the screening of active components in TCM often overlook trace components owing to their concealment by more abundant constituents. To address this limitation, a fishing strategy based on offline two-dimensional liquid chromatography (2D-LC) combined with surface plasmon resonance (SPR) was utilized to screen bioactive trace components targeting peroxiredoxin 3 (PRDX3), using Uncaria alkaloids (UAs) as a case study. Initially, an orthogonal preparative offline 2D-LC system combining a positively charged C₁₈ column and a conventional C₁₈ column under disparate mobile phase conditions was constructed. To fully reveal the trace alkaloids, 13 2D fractions of UAs were prepared, and their components were characterized using mass spectrometry (MS). Subsequently, employing PRDX3 as the targeting protein, a SPR-based screening approach was established and rigorously validated with geissoschizine methyl ether (GSM) serving as a positive control for binding. Employing this refined strategy, 29 candidate binding alkaloids were fished from the 13 2D fractions. Notably, combining offline 2D-LC with SPR increased the yield of candidate binding components from 10 to 29 when compared to SPR-based screening alone. Subsequent binding affinity assays confirmed that PRDX3 was a direct binding target for the 12 fished alkaloids, with isovallesiachotamine (IV), corynoxeine N-oxide (CO-N), and cadambine (CAD) demonstrating the highest affinity for PRDX3. Their interactions were further validated through molecular docking analysis. Subsequent intracellular H₂O₂ measurement assays and transfection experiments confirmed that these three trace alkaloids enhanced PRDX3-mediated H₂O₂ clearance. In conclusion, this study introduced an innovative strategy for the identification of active trace components in TCM. This approach holds promise for accelerating research on medicinal components within this field.

Objective To learn the effect of breast removal of polyacrylamide hydrogel by areola incision;and to provide an effective method for removal of polyacrylamide hydrogel.Methods According to the accepted operation,45 cases with breast polyacrylamide hydrogel were divided into 25 cases of observation group and 20 cases of control group.The observation group was treated with areola medial semicircular incision breast removal of polyac-rylamide hydrogel,and the control group was treated with areola small incision suction to remove polyacrylamide hydrogel.The operative time,intraoperative blood loss,postoperative drainage tube extraction time,postoperative 7d breast shape and perioperative complications of the two groups were observed;postoperative follow -up was performed to evaluate the effect of surgery.Results The operation time of the observation group (190.2 ±36.1)min was longer than (119.5 ±44.0)min of the control group,the difference was statistically significant between the two groups (t =5.924,P <0.05);the intraoperative blood loss of the observation group (250.4 ±23.9)mL was higher than (89.7 ± 30.4)mL of the control group,the difference was statistically significant (t =19.865,P <0.05 ).The difference between postoperative 7d breast normal morphology rates of the two groups was not statistically significant (χ2 =2.571,P >0.05);the postoperative drainage tube extraction time of the observation group (3.7 ±0.5)d was more than (2.3 ±0.3)d of the control group,the difference was statistically significant (t =11.021,P <0.05 ).The complication rate of the observation group was 12.0%(3 /25),which of the control group was 10.0%(2 /20),the difference was not statistically significant (χ2 =0.045,P >0.05).All cases of the two groups were followed up;the mean follow -up time was (6.7 ±2.1)months.The good rate of surgery of the observation group was 92.0 % (23 /25),which of the control group was 70.0%(14 /20),the observation group was higher than the control group (χ2 =5.718,P <0.05).Conclusion For patients with complications after polyacrylamide hydrogel injection for augmentation mammoplasty;the breast polyacrylamide hydrogel removal surgery by areola medial semicircular incision is recommen-ded as the preferred.

Objective To explore the factors related to the delayed graft function (DGF). Methods Clinical data of 150 recipients were collected and performed by Cox proportional hazards regression analysis . In addition, the glutathione S-transferase (GST) gene polymorphism of 172 donors and 157 healthy persons was analyzed by multiple PCR and SSP-PCR. Results DGF was observed in 24 patients among 150 recipients. Pretranplantation dialysis mode, PR A levels and recipient gender were uncorrelated with the incidence of DGF(P>0. 05). Urinary volume of the second 24 hours after transplantation was an independent predictor of DGF(RR=1. 002, P = 0. 001). The frequency of donor's null GSTM1 in DGF group was significantly higher than that in non-DGF group(P<0. 05). Conclusions Urinary volume of the second 24 hours after transplantation could be a predictor for DGF. The null GSTM1 in donor might be one of the factors related to the EGF.

Succinic acid has received a great deal of attention as an important green chemical stock for the manufacture of synthetic resins, biodegradable polymers and chemical intermediates. In this paper, the breeding mechanism of Actinobacillus succinogenes based on metabolic flux analysis was demonstrated to improve the yield of succinic acid by fermentation. After the NTG treatment, mutants from A. succinogenes CGMCC 1593 which were able to grow in medium containing concentrations of about 50-100 mmol/L of sodium monofluoroacetate were obtained. Among them, a mutant SF-9 was selected for producing more succinic acid and less acetic acid. When fermentations were conducted in a 5 L bioreactors, the final succinic acid concentration of SF-9 (34.8 g/L) increased 23.4%, and the mass ratio of succinic acid/acetic acid increased from 3.3 to 9 compared with those of the parent strain. Based on the metabolic flux analysis of A. succinogenes, PEP was found to be a key node which has an important effect on the production of succinic acid, and the flux ratio of by-productions (acetic, formic, lactic acid) was influenced by PYR node. Compared with the parent strain, the flux to succinic acid of mutant (A. succinogenes SF-9) was significantly increased, while the flux to by-productions had an obvious decline. Therefore, PEP and PYR are not rigid nodes in the metabolic regulation of A. succinogenes.
Actinobacillus ; genetics ; growth & development ; metabolism ; Drug Tolerance ; Fermentation ; Fluoroacetates ; metabolism ; Metabolic Networks and Pathways ; Mutation ; Succinic Acid ; metabolism

In anaerobic bottles fermentation,glucose,fructose,xylose,lactose,maltose,sucrose and sugar alcohols could be used to produce succinic acid with Actinobacillus succinogenes. When sorbitol was utilized as the carbon source in the batch fermentation,more succinate and ethanol were produced compared with those using glucose,while producing less acetate and formate. The metabolic flux analysis results showed that the flux partitioning at PEP node was stable when glucose was replaced by sorbitol,but the flux partitioning at PYR and AcCoA nodes changed a lot because more reducing power(NADH) was generated to meet the more requirement the synthesis of succinate and ethanol.

Differential treatment based on signs and symptoms is the special points of TCM,the identification of syndrome is the basis of differential treatment.Scientific research on syndrome plays a leading role in unifying pathogenesis of dyslipidemia,and certainly improves the research level of dyslipidemia in TCM.According to the status quo of lipid abnormality research,the research in this field can be conducted in two aspects in priority:firstly,the research of subjective symptoms can provide some basis for TCM research;secondly,the associativity of TCM syndromes and the metabolic syndromes is advantageous for exploring the nature and rules of lipid abnormality in TCM,it will be helpful for the improvement of lipid abnormality differentiation and treatment.