Regulation of optimized new Shengmai powder on cardiomyocyte apoptosis and ferroptosis in ischemic heart failure rats: The mediating role of phosphatidylinositol-3-kinase/protein kinase B/tumor protein 53 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Optimized New Shengmai Powder (ONSMP) is a sophisticated traditional Chinese medicinal formula renowned for bolstering vital energy, optimizing blood circulation, and mitigating fluid retention. After years of clinical application, ONSMP has shown a significant impact in improving myocardial injury and cardiac function and has a positive effect on treating heart failure. However, many unknowns exist about the molecular biological mechanisms of how ONSMP exerts its therapeutic effects, which require further research and exploration. AIM OF THE STUDY: Exploring the potential molecular biological mechanisms by which ONSMP ameliorates cardiomyocyte apoptosis and ferroptosis in ischemic heart failure (IHF). MATERIALS AND METHODS: First, we constructed a rat model of IHF by inducing acute myocardial infarction through surgery and using echocardiography, organ coefficients, markers of heart failure, antioxidant markers, and histopathological examination to assess the effects of ONSMP on cardiomyocyte apoptosis and ferroptosis in IHF rats. Next, we used bioinformatics analysis techniques to analyze the active components, signaling pathways, and core targets of ONSMP and calculated the interactions between core targets and corresponding elements. Finally, we detected the positive expression of apoptosis and ferroptosis markers and core indicators of signaling pathways by immunohistochemistry; detected the mean fluorescence intensity of core indicators of signaling pathways by immunofluorescence; detected the protein expression of signaling pathways and downstream effector molecules by western blotting; and detected the mRNA levels of p53 and downstream effector molecules by quantitative polymerase chain reaction. RESULTS: ONSMP can activate the Ser83 site of ASK by promoting the phosphorylation of the PI3K/AKT axis, thereby inhibiting the MKK3/6-p38 axis and the MKK4/7-JNK axis signaling to reduce p53 expression, and can also directly target and inhibit the activity of p53, ultimately inhibiting p53-mediated mRNA and protein increases in PUMA, SAT1, PIG3, and TFR1, as well as mRNA and protein decreases in SLC7A11, thereby inhibiting cardiomyocyte apoptosis and ferroptosis, effectively improving cardiac function and ventricular remodeling in IHF rat models. CONCLUSION: ONSMP can inhibit cardiomyocyte apoptosis and ferroptosis through the PI3K/AKT/p53 signaling pathway, delaying the development of IHF.

Double-endpoint Genotoxicity Quantification and PAHs Characterization of Drinking Water Source alongside Polluted Yinghe River with High Tumor Mortality.

The etiology for the high tumor mortality in heavy polluted Yinghe river basin is still unclear and polycyclic aromatic hydrocarbons (PAHs) belong to the priority pollutants in water based on the former surveillance data. In order to explore the potential genotoxicants contributing to the double-endpoint genotoxicity of polluted drinking water source, 12 groundwater and 3 surface water samples were collected from 3 villages and the nearby rivers alongside Yinghe river basin, respectively and their comprehensive genotoxicity was estimated with a bioassay group of SOS/umu test and micronucleus (MN) test (MNT). Some groundwater samples showed positive genotoxicity and all surface water samples were highly genotoxic. Eight groundwater samples showed DNA genotoxic effect with the average 4-NQO equivalent concentration (TEQ(4-NQO)) of 0.067 µg/L and 0.089 µg/L in wet and dry season, respectively. The average MN ratios of groundwater samples were 14.19‰ and 17.52‰ in wet and dry season, respectively. Groundwater samples showed different genotoxic effect among 3 villages. The total PAHs concentrations in all water samples ranged from 8.98 to 25.17 ng/L with an average of 14.97±4.85 ng/L. BaA, CHR, BkF, BaP and DBA were the main carcinogenic PAHs contributing to the genotoxicity of water samples. In conclusion, carcinogenic PAHs are possibly related to the high tumor mortality in the target area. Characterization of carcinogenic PAHs to genotoxicity of drinking water source may shed light on the etiology study for high tumor mortality in Yinghe river basin.

Source, Characterization of Indoor Dust PAHs and the Health Risk on Chinese Children.

Polycyclic aromatic hydrocarbons (PAHs) in indoor dust are one of the common exposure sources for children worldwide. The aim of this study is to explore PAHs pollution status in indoor dust and estimate health risk on Chinese children with big data. Weighted average concentration was used to analyze source and characterization of PAHs in indoor dust based on peer-reviewed literature. According to specific inclusion criteria, 17 studies were included finally to analyze weighted average concentration. The national average concentration of Σ16PAHs was approximately 25.696 µg/g. The highest concentration of Σ16PAHs was in Shanxi (2111.667 µg/g), and the lowest was in Hong Kong (1.505 µg/g). The concentrations in Shanxi and Guangdong were higher than national level and the over standard rate was 18.18%. The concentrations of individual PAHs varied greatly across the country, and Flu in Shanxi was the highest (189.400 µg/g). The sources of PAHs varied in different regions and combustion processes played a leading role. PAHs exposure through ingestion and dermal contact was more carcinogenic than inhalation. The incremental lifetime cancer risk model indicated that children lived in Shanxi were found in the highest health risk coupled with the highest BaPE concentration (54.074 µg/g). Although PAHs concentrations of indoor dust showed a downward trend from 2005 to 2018, indoor environmental sanitation should be improved with multidisciplinary efforts. Health standard should be possibly established to minimize children exposure to PAHs in indoor dust in China.

Study on the influence of curcumin on chemosensitivity of nephroblastoma cells.

OBJECTIVE: To study the influence of curcumin on chemosensitivity of nephroblastoma cells. METHODS: Human nephroblastoma cells line SK-NEP-1 was transplanted to the nude mice subcutaneously to establish the implantation tumor model of human nephroblastoma cells. A total of 30 tumor-bearing mice were divided into three groups of ten randomly. The routine chemotherapy group was given vincristine (0.05 mg/mL·0.2 mL/d) and actinomycin D (15 ng/mL·0.2 mL/d) combined chemotherapy regime. The curcumin chemotherapy group was given the same combined chemotherapy regimens and curcumin (30 mg/kg/d) by intraperitoneal injection. The control group was given normal saline (NS) of the same volume by intraperitoneal injection. Continuous administration would be kept for 4 weeks and 3 days a week. The volumetric changes of every group were recorded. The serum of every group in different time was collected and the VEGF content was detected by ELISA. All mice were cercrificed and the tumor tissues were stripped and weighed after 4 weeks' treatment. The tumor inhibition rate was calculated. The cell proliferation activity and apoptosis rate were detected by MTT and flow cytometry method. All data were statistically analyzed by SPSS 19.0. RESULTS: The tumor volume, serum VEGF content, tumor inhibition rate, cell proliferation activity and apoptosis rate of routine chemotherapy group and curcumin chemotherapy group had significant differences comparing with the control group (P < 0.05) after 4-week's treatment. The cancer growth of curcumin chemotherapy group was obviously decreased and even tended to shrink comparing with routine chemotherapy group (χ(2) = 15.732, P = 0.007). The cell proliferation activity was significantly reduced and the apoptosis rate was significantly higher, (χ(2) = 9.427, P = 0.012) which showing the effect of chemotherapy was enhanced. CONCLUSIONS: The chemosensitivity of nephroblastoma cells could be improved by curcumin, then the effect of preoperative adjuvant chemotherapy scheme would be enhanced, the growth of nephroblastoma cells would be inhibited and the surgical risk of nephroblastoma would be reduced.

Effect of Qi-regulating,Phlegm-resolving,and Blood-promoting Prescription on Rat Coronary Microvascular Thrombosis and Coronary Microvascular Occlusion.

Objective To explore the effect of qi-regulating,phlegm-resolving,and blood-promoting prescription on coronary microvascular thrombosis and coronary microvascular occlusion in rat models. Methods Totally 125 healthy clean-grade male SD rats weighing (300±25) g were sequentially numbered and then randomly divided into treatment group (n=60),control group (n=60) and blank group (n=5).Rats in the treatment group and control group received apical left ventricular injection of sodium laurate to establish rat models of coronary microvascular thrombosis. Then,rats in the control group were given distilled water by gavage one day before operation and after surgery. In contrast,rats in the treatment group were given qi-regulating,phlegm-resolving,and blood-promoting prescription by gavage one day before operation and after surgery. Five rats from both treatment group and control group were killed at each of six time points (1 hour,24th hour,7th day,14th day,21th day,and 28th day),and the myocardium specimens were harvested. The 5 rats in the blank group did not receive any special treatment and were given normal feeding;in the 28th day,they were sacrificed to obtain the myocardial specimens. Pathological sections of rat myocardial tissues were made to observe and compare the degrees of coronary microvascular thrombosis and coronary microvascular obstruction.Results In the treatment group and the control group,coronary microvascular thrombosis occurred 1 hour after apical sodium laurate injection and reached the peak at the 24th hour. Compared with the blank group,the treatment group and the control group showed different degree of coronary microvascular obstruction. Comparison between the treatment group and the control group at each time point showed that the coronary microvascular thrombosis in the treatment group was significantly lower than that in the control group (P<0.05 or P<0.01).The severity of coronary microvascular occlusion was significantly milder in the treatment group than in the control group (P<0.05 or P<0.01).Conclusions Apical left ventricular injection of sodium laurate successfully established rat models of coronary microvascular thrombosis. Qi-regulating,phlegm-resolving,and blood-promoting prescription can reduce coronary microvascular thrombosis and improve coronary microvascular obstruction.

Quantification for total demethylation potential of environmental samples utilizing the EGFP reporter gene.

The demethylation potential of pollutants is arguably an innate component of their toxicity in environmental samples. A method was developed for determining the total demethylation potential of food samples (TDQ). The demethylation epigenetic toxicity was determined using the Hep G2 cell line transfected with pEGFP-C3 plasmids containing a methylated promoter of the EGFP reporter gene. The total demethylation potential of the sample extracts (the 5-AZA-CdR demethylation toxic equivalency) can be quantified within one week by using a standard curve of the 5-AZA-CdR demethylation agent. To explore the applicability of TDQ for environmental samples, 17 groundwater samples were collected from heavy polluted Kuihe river and the total demethylation potentials of the sample extracts were measured successfully. Meaningful demethylation toxic equivalencies ranging from 0.00050 to 0.01747µM were found in all groundwater sample extracts. Among 19 kinds of inorganic substance, As and Cd played important roles for individual contribution to the total demethylation epigenetic toxicity. The TDQ assay is reliable and fast for quantifying the DNA demethylation potential of environmental sample extracts, which may improve epigenetic toxicity evaluations for human risk assessment, and the consistent consuming of groundwater alongside the Kuihe river pose unexpected epigenetic health risk to the local residents.