[Chaihu Sanshen Capsules protect rats from myocardial ischemia reperfusion injury via PKCßâ ¡/NOX2/ROS signaling pathway].

This study aims to explore the pathogenesis of myocardial ischaemia reperfusion injury(MIRI) based on oxidative stress-mediated programmed cell death and the mechanism and targets of Chaihu Sanshen Capsules in treating MIRI via the protein kinase Cß(PKCßⅡ)/NADPH oxidase 2(NOX2)/reactive oxygen species(ROS) signaling pathway. The rat model of MIRI was established by the ligation of the left anterior descending branch. Rats were randomized into 6 groups: sham group, model group, clinically equivalent-, high-dose Chaihu Sanshen Capsules groups, N-acetylcysteine group, and CGP53353 group. After drug administration for 7 consecutive days, the area of myocardial infarction in each group was measured. The pathological morphology of the myocardial tissue was observed by hematoxylin-eosin(HE) staining. The apoptosis in the myocardial tissue was observed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL). Enzyme-linked immunosorbent assay(ELISA) was employed to measure the le-vels of indicators of myocardial injury and oxidative stress. The level of ROS was detected by flow cytometry. The protein and mRNA levels of the related proteins in the myocardial tissue were determined by Western blot and real-time quantitative PCR(RT-qPCR), respectively. Compared with the sham group, the model group showed obvious myocardial infarction, myocardial structural disorders, interstitial edema and hemorrhage, presence of a large number of vacuoles, elevated levels of myocardial injury markers, myocardial apoptosis, ROS, and malondialdehyde(MDA), lowered superoxide dismutase(SOD) level, and up-regulated protein and mRNA le-vels of PKCßⅡ, NOX2, cysteinyl aspartate specific proteinase-3(caspase-3), and acyl-CoA synthetase long-chain family member 4(ACSL4) in the myocardial tissue. Compared with the model group, Chaihu Sanshen Capsules reduced the area of myocardial infarction, alleviated the pathological changes in the myocardial tissue, lowered the levels of myocardial injury and oxidative stress indicators and apoptosis, and down-regulated the mRNA and protein levels of PKCßⅡ, NOX2, caspase-3, and ACSL4 in the myocardial tissue. Chaihu Sanshen Capsules can inhibit oxidative stress and programmed cell death(apoptosis, ferroptosis) by regulating the PKCßⅡ/NOX2/ROS signaling pathway, thus mitigating myocardial ischemia reperfusion injury.

Role of phosphate in microalgal-bacterial symbiosis system treating wastewater containing heavy metals.

Phosphorus is one of the important factors to successfully establish the microalgal-bacterial symbiosis (MABS) system. The migration and transformation of phosphorus can occur in various ways, and the effects of phosphate on the MABS system facing environmental impacts like heavy metal stress are often ignored. This study investigated the roles of phosphate on the response of the MABS system to zinc ion (Zn2+). The results showed that the pollutant removal effect in the MABS system was significantly reduced, and microbial growth and activity were inhibited with the presence of Zn2+. When phosphate and Zn2+ coexisted, the inhibition effects of pollutants removal and microbial growth rate were mitigated compared to that of only with the presence of Zn2+, with the increasing rates of 28.3% for total nitrogen removal, 48.9% for chemical oxygen demand removal, 78.3% for chlorophyll-a concentration, and 13.3% for volatile suspended solids concentration. When phosphate was subsequently supplemented in the MABS system after adding Zn2+, both pollutants removal efficiency and microbial growth and activity were not recovered. Thus, the inhibition effect of Zn2+ on the MABS system was irreversible. Further analysis showed that Zn2+ preferentially combined with phosphate could form chemical precipitate, which reduced the fixation of MABS system for Zn2+ through extracellular adsorption and intracellular uptake. Under Zn2+ stress, the succession of microbial communities occurred, and Parachlorella was more tolerant to Zn2+. This study revealed the comprehensive response mechanism of the co-effects of phosphate and Zn2+ on the MABS system, and provided some insights for the MABS system treating wastewater containing heavy metals, as well as migration and transformation of heavy metals in aquatic ecosystems.

Eudesmane sesquiterpenoids with inhibitory effects on NO production from Artemisia princeps.

Five undescribed eudesmane methyl esters (1-5), three undescribed eudesmane-12,6-olides (6-8), and 21 known analogues (9-29) were isolated from the aerial part of Artemisia princeps Pamp. Their structures were established by detailed analysis of the NMR and HRESIMS data. The absolute configurations of 1-8 were determined based on single-crystal X-ray diffraction analysis and ECD calculations. Moreover, the inhibitory effects on LPS-induced NO production in BV-2 microglial cells of all the isolated compounds were assessed. Except for compounds 2, 4, 10, and 11, the others showed significant inhibitory activities, with IC50 values of 0.73-18.66 µM, wherein the potential structure-activity relationship was also discussed.

Three new phenolic glycosides and a new lignan glycoside from Gaultheria leucocarpa var. yunnanensis.

Three new phenolic glycosides (1-3) and a new lignan glycoside (4), together with five known compounds (5-9) were isolated from the ethanol extract of the aerial part of Gaultheria leucocarpa var. yunnanensis (Franch.) T.Z.Hsu & R.C.Fang. Their structures were determined on the basis of spectroscopic techniques, experimental and calculated ECD spectra, acid hydrolysis, and enzymatic hydrolysis experiments. All the isolates were evaluated for their anti-inflammatory and antioxidant activities. Compounds 7 and 8 exhibited inhibitory effects against the LPS-induced production of NO with IC50 of 63.71 and 10.66 µM, respectively, compared to L-NMMA having an IC50 of 6.95 µM. Besides, compound 7 also represented significant DPPH radical scavenging activity with EC50 of 18.75 µM, comparable with vitamin C (EC50 = 15.77 µM).

Structurally diverse spirocyclic polycyclic polyprenylated acylphloroglucinols from Hypericum ascyron Linn. and their anti-tumor activity.

Ten spirocyclic polycyclic polyprenylated acylphloroglucinols (PPAP), hunascynols A-J (1-10), and 12 known analogs were isolated from the aerial parts of Hypericum ascyron Linn. Compounds 1 and 2, which share a 1,2-seco-spirocyclic PPAP skeleton, could be derived from spirocyclic PPAP, with a common octahydrospiro[cyclohexan-1,5'-indene]-2,4,6-trione core, through a cascade of Retro-Claisen, keto-enol tautomerism, and esterification reactions. Aldolization of normal spirocyclic PPAP yielded 3, which has a caged framework with a 6/5/6/5/6 ring system. The structures of these compounds were determined using spectroscopy and X-ray diffraction. The inhibitory activities of all isolates were tested in three human cancer cell lines and a zebrafish model. Compounds 1 and 2 displayed moderate cytotoxicity against HCT116 cells (IC50 6.87 and 9.86 µM, respectively). The mechanisms of these compounds were evaluated using Western blot assays. Compounds 3 and 5 inhibited the growth of sub-intestinal vessels in zebrafish embryos. Further, the target genes were screened using real-time PCR.

Effects of Chinese fir planting and phosphorus addition on soil microbial biomass and extracellular enzyme activities.

Plants can alter soil microbial biomass and extracellular enzyme activities related with carbon (C), nitrogen (N), and phosphorus (P), through litter and root exudates, with consequences on soil carbon, nitrogen and phosphorus (P) cycling. However, it is not well known how the changes in soil phosphorus availability affect the relationships between plants and soil microorganisms. In this study, a factorial experiment was conducted to investigate the effects of Chinese fir (Cunninghamia lanceolata) planting and different levels of P addition (0, 1.95, 3.9, 7.8 and 15.6 g P·m-2·a-1) on soil microbial biomass and extracellular enzyme activities. The results showed that planting Chinese fir planting significantly altered soil microbial biomass and C- and N- and P-related extracellular enzyme activities, but the effects were dependent on P addition levels. Without P addition, Chinese fir planting significantly reduced soil nutrient availability and pH, which led to the aggravation of P limitation and lower soil microbial biomass. P addition relieved P limitation, and reduced soil acid phosphatase (ACP) activities by 30.0%, 30.5%, 35.3% and 47.1% with the increasing P addition level (1.95, 3.9, 7.8 and 15.6 g P·m-2·a-1). Under three P addition levels (1.95, 3.9 and 7.8 g P·m-2·a-1), the negative effects of Chinese fir planting on soil microbial growth were alleviated. Under the high P addition level (15.6 g P·m-2·a-1), the negative effects of Chinese fir planting on soil microbial growth occurred again due to soil N limitation. Taken together, Chinese fir planting and soil P availability generally affected soil microbial biomass and extracellular enzyme activities, and changed P limitation.

[Regulation of myocardial ischemia reperfusion injury signal pathway by flavonoid monomer].

Acute myocardial infarction seriously endangers the health of people due to its high morbidity and high mortality. Reperfusion strategy is the preferred treatment strategy for acute myocardial infarction. However, reperfusion may lead to additional heart damage, namely myocardial ischemia reperfusion injury(MIRI). Therefore, how to reduce myocardial ischemia reperfusion injury has become one of the urgent problems to be solved in cardiovascular disease. Traditional Chinese medicine(TCM) has the multi-component, multi-channel, and multi-target advantages in the treatment of MIRI, which offers new ideas in this aspect. TCM containing flavonoids has a variety of biological activities and plays a significant role in the treatment of MIRI, which has great research and development application value. TCM containing flavonoids can regulate multiple signaling pathways of MIRI, such as phosphatidylinositol 3 kinase/kinase B(PI3K/Akt) signaling pathway, Janus kinase/signal transducer and activator of transcriptions(JAK/STAT) signaling pathway, adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK) signaling pathway, mitogen-activated protein kinase(MAPK) signaling pathway, nuclear factor-erythroid 2-related factor 2/antioxidant response element(Nrf2/ARE) signaling pathway, nuclear factor kappa-B(NF-κB) signaling pathway, silent information regulator 1(Sirt1) signaling pathway, and Notch signaling pathway. It reduces MIRI by inhibiting calcium overload, improving energy metabolism, regulating autophagy, and inhibiting ferroptosis and apoptosis. Therefore, a review has been made based on the regulation of relative signaling pathways against MIRI by TCM containing flavonoids, thus providing theoretical support and potential therapeutic strategies for TCM to alleviate MIRI.

Integrating metabolomics and lipidomics revealed a decrease in plasma fatty acids but an increase in triglycerides in children with drug-refractory epilepsy.

OBJECTIVE: The drug-refractory epilepsy (DRE) in children is commonly observed but the underlying mechanisms remain elusive. We examined whether fatty acids (FAs) and lipids are potentially associated with the pharmacoresistance to valproic acid (VPA) therapy. METHODS: This single-center, retrospective cohort study was conducted using data from pediatric patients collected between May 2019 and December 2019 at the Children's Hospital of Nanjing Medical University. Ninety plasma samples from 53 responders with VPA monotherapy (RE group) and 37 non-responders with VPA polytherapy (NR group) were collected. Non-targeted metabolomics and lipidomics analysis for those plasma samples were performed to compare the potential differences of small metabolites and lipids between the two groups. Plasma metabolites and lipids passing the threshold of variable importance in projection value >1, fold change >1.2 or <0.8, and p-value <0.05 were regarded as statistically different substances. RESULTS: A total of 204 small metabolites and 433 lipids comprising 16 different lipid subclasses were identified. The well-established partial least squares-discriminant analysis (PLS-DA) revealed a good separation of the RE from the NR group. The FAs and glycerophospholipids status were significantly decreased in the NR group, but their triglycerides (TG) levels were significantly increased. The trend of TG levels in routine laboratory tests was in line with the lipidomics analysis. Meanwhile, cases from the NR group were characterized by a decreased level of citric acid and L-thyroxine, but with an increased level of glucose and 2-oxoglutarate. The top two enriched metabolic pathways involved in the DRE condition were biosynthesis of unsaturated FAs and linoleic acid metabolism. SIGNIFICANCE: The results of this study suggested an association between metabolism of FAs and the medically intractable epilepsy. Such novel findings might propose a potential mechanism linked to the energy metabolism. Ketogenic acid and FAs supplementation might therefore be high-priority strategies for DRE management.