Search

Carpesium abrotanoides L. is rich in sesquiterpene lactones, the experiments of anti-tumor activity in vitro showed that total sesquiterpene lactone extracts exhibited the most cytotoxicity activities against HepG-2 cells (IC50 = 4.2 μg/mL). In order to isolated the active compounds quickly, the strategy of HPLC-ESI-Q-TOF-MS/MS combined with high-speed counter-current chromatography (HSCCC) was implemented. Three sesquiterpene lactone compounds, 2α,5α-dihydroxy-11αH-eudesma-4(15)-en-12,8β-olide (1), telekin (2), oxoeudesm-11(13)-eno-12,8α-lactone (3) were obtained. Their structures were elucidated by detailed analysis of 1D, 2D NMR and HRMS data. In addition, compounds 1-3 were evaluated for their cytotoxic activities against HepG-2 cell line with IC50 value of 9.83, 2.95, and 4.15 μM, respectively. Moreover, all compounds not only can reduce the expression of JAK2 and STAT3 mRNA but also inhibit the p-JAK2 and p-STAT3 protein expression levels in a dose‐dependent manner in the HepG-2 cells. In conclusion, three sesquiterpene lactone compounds inhibited the proliferation of HepG-2 cells via suppressing the JAK2/STAT3 signaling pathway.

The content of free calcium oxide (f-CaO) in clinker significantly determines the quality of the final cement production. However, in practice, the value of f-CaO content in clinker is off-line sampled manually with a significant time interval and then analyzed in a laboratory with a large time delay, which could meet the needs for monitoring and control of cement quality. To tackle this problem, this article proposes a data-driven model based on deep dynamic features extracting and transferring methods to build a virtual sensor for f-CaO content prediction. First, in this model, large-scale unlabeled data collected from the process distributed control system (DCS) take a vital effect in extracting nonlinear dynamic features along with the limited labeled data samples. Then, the extracted features are transferred to a powerful regression model, the eXtreme Gradient Boosting (XGBoost), for output f-CaO prediction. Besides, an incremental model updating strategy is proposed for the augment of online data samples, which facilitates the virtual sensor to adapt the process time-variant characteristics. Finally, the proposed virtual sensor is verified by a data set acquired from a real cement production process. Comparing with traditional statistical modeling methods, the prediction accuracy of f-CaO content is significantly improved.

Foshou San is a typical gynaecological formula with wild usage in traditional Chinese medicine. Jiawei Foshou San (JFS) is a novel ingredient prescription from Foshou San with antiendometriosis effect in unclear mechanisms. To uncover the potential application and proapoptotic mechanisms of JFS, JFS ingredient-drug target-disease networks, GO enrichment, and pathway analysis were established for potential application prediction. Molecular docking and validation in vivo were investigated by the proapoptotic mechanisms of JFS. In this study, 99 common targets were related to 108 diseases. 484 biological processes, 44 cell components, 59 molecular functions, and 37 pathways were significantly identified in GO enrichment and pathway analysis. In molecular docking, ligustrazine showed binding activity with Bcl-2, Bax, caspase-9, caspase-3, and PARP. In vivo, JFS elevated the shrink rate of ectopic endometrium, by suppressing E2 and PROG. An in-depth study showed that apoptosis was activated through diminishing Bcl-2, rising Bax and Bad, and expressing more caspase-3 and caspase-9 using JFS. JFS promoted the protein level of cleaved-PARP. In brief, JFS might be applied for various diseases through multiple targets and pathways, especially endometriosis by Bcl-2 pathway. These findings reveal the potential application for further evaluation and uncover the proapoptotic mechanism of JFS.

Six flavonoid glycosides jixueqisus A-F, together with nine known flavonoids, were isolated from the rhizomes of the fern Pronephrium penangianum. Among them, two red pigments jixueqisus A and B possess the same rare 6,8-dimethyl-2-phenyl-7H-1-benzopyran-7-one skeleton (a long conjugated system). Jixueqisu Cwas a dihydrochalcone glycoside, jixueqisu D was a chalcone glycoside, jixueqisu E was an aurone glycoside, and jixueqisu F was a flavonone glycoside. Interestingly, jixueqisus D-F, (2S)-5,2',5'-trihydroxy-7-methoxyflavanone and 5,2',5'-trihydroxy-7-methoxyflavone possessed a 2,5-dihydroxy substituted benzene ring (B-ring). Their structures were elucidated by various spectroscopic and chemical methods. Furthermore, the plausible biosynthetic pathways of jixueqisus A-F were discussed, respectively. All isolated compounds were evaluated for their activities against the proliferation of MCF-7, HepG-2, HCT-116 and BGC-823 tumor cell lines, four known flavane-4-ol glycosides, abacopterins A and C, eruberin B and triphyllin A, exhibited moderate activities to various cell lines.

Glutathione (GSH) levels are closely related to the homeostasis of redox state which directly affects human disease occurrence by regulating cell apoptosis. Hence, real-time monitoring of dynamic changes in intracellular GSH levels is urgently needed for disease early diagnosis and evaluation of therapy efficiency. In this study, an endogenous cysteine (Cys)-assisted detection system based on GSH@AgNCs and reduced graphene oxide (rGO) with high sensitivity and specificity was developed for GSH detection. Compared with GSH, GSH@AgNCs with weaker affinity and bonding force was quite easier to extrude from the rGO surface when competing against GSH, leading to the obvious change in fluorescence signal. This phenomenon was termed as "a crowding out effect". Furthermore, the presence of Cys can improve GSH assay sensitivity by enhancing the quenching efficiency of rGO on the GSH@AgNCs. In vitro assay indicated that the efficiency of fluorescence recovery was positively related with GSH concentration in the range from 0 to 10 mM. In addition, the method was employed for real-time monitoring of the dynamic changes in GSH levels regulated by natural drugs. The imaging results showed that the natural compound 3 (C3) can downregulate GSH levels in HepG2 cells, which was accompanied by reactive oxygen species (ROS) release and apoptosis induction. Finally, the method was used to monitor the change of GSH levels in serum samples with chronic hepatitis B (CHB) infection. The results demonstrated that the occurrence and development of CHB may be positively correlated with GSH levels to some extent. Overall, the above results demonstrate the potential application of this new nanosystem in anticancer natural drug screening and clinical assay regarding GSH levels.

Seven undescribed indole-based alkaloids, xuefengins A–D and xuefenglasins A–C, were isolated from natural Ophiocordyceps xuefengensis, along with six known alkaloids. Their structures were elucidated by comprehensive spectroscopy, with absolute configurations confirmed by comparison with calculated electronic circular dichroism spectra. Eleven of the isolates were tested for cytotoxicity against the U937, NB4, MCF-7, Hep G2, and A549 cancer cell lines. Two compounds exhibited moderate activities, with IC50 values of 2.83–25.68 μM and 1.54–12.16 μM. Further pharmacological studies showed that these two compounds inhibit cell proliferation by inducing apoptosis, and decreasing p38 and caspase-3 levels in A549 cells.

Necroptosis, oxidative stress, and inflammation are major contributors to the pathogenesis of ischemic acute kidney injury. Necrostatin-1 (Nec-1), an inhibitor of the kinase domain of receptor-interacting protein kinase-1 (RIP1), has been reported to regulate renal ischemia and reperfusion (I/R) injury; however, its underlying mechanism of action remains unclear. HK-2 cells were used to create an in vitro I/R model, in which the cells were subjected to hypoxia, followed by 2, 6, and 12 h of reoxygenation. For the in vivo study, a rat model of renal I/R was established in which samples of rat blood serum and kidney tissue were harvested after reperfusion to assess renal function and detect histological changes. Cell viability and necroptosis were analyzed using the Cell Counting Kit (CCK)-8 assay and flow cytometry, respectively. The expression levels of molecules associated with necroptosis, oxidative stress, and inflammation were determined by real-time PCR, western blotting, immunofluorescence staining, and ELISA. Luciferase and chromatin immunoprecipitation (ChIP) assays were performed to confirm the relevant downstream signaling pathway. We found that pretreatment with Nec-1 significantly decreased hypoxia-inducible factor-1α (HIF-1α) and miR-26a expression, as well as the levels of factors associated with necroptosis (RIP1, RIP3, and Sirtuin-2), oxidative stress (malondialdehyde [MDA], NADP+/NADPH ratio), and inflammation (interleukin [IL]-1β, IL-10, and tumor necrosis factor alpha [TNF-α]) in I/R injury cells and the rat model. However, these effects could be reversed by miR-26a overexpression or TRPC6 knockdown. Mechanistic studies demonstrated that HIF-1α directly binds to the promoter region of miR-26a, and that TRPC6 is a potential target gene for miR-26a. Our findings indicate that Nec-1 can effectively protect against renal I/R injury by inhibiting necroptosis, oxidative stress, and inflammation, and may exert its effects through mediation of the HIF-1α/miR-26a/TRPC6/PARP1 signaling pathway. Keywords: ischemic/reperfusion injury, Nec-1, HIF-1α, miR-26a, TRPC6, necroptosis, oxidative stress, inflammation

This paper intends to identify the antimicrobial activity compounds from the deciduous leaves of Malus doumeri (Dong Li Tea) by HPLC-ESI-QTOF-MS/MS. The ethanol extracts of Malus doumeri were partitioned into petroleum ether, dichloromethane, ethyl acetate, n-butanol and water fraction, respectively. The antimicrobial screening experiments showed that ethyl acetate fraction has a certain antibacterial activity by inhibition zone method in vitro. And then we used the HPLC-ESI-QTOF-MS/MS method to verify the identities of bioactive compounds. Finally, 41 compounds were determined and 11 of which were firstly reported in this plant. Notably, compounds (32, 34, 38) are new dihydrochalcones, and three chlorogenic acid analogues (10, 13, 17) may be potential antimicrobial active ingredient. Which is of great significance to the isolation of novel compounds and the discovery of new natural preservative candidates from the deciduous leaves of Malus doumeri.

Caterpillar fungi have numerous pharmacological and therapeutic applications in traditional medicine, due to a variety of active chemical constituents, such as cordycepin and adenosine. It is imperative to discover new resource for artificial cultivation and biometabolite production since the traditional natural species are endangered. In this study, a new strain HACM 001 was isolated and identified as Ophiocordyceps xuefengensis by rDNA-ITS sequencing. This strain showed the potential of artificial infection to caterpillar larvae leading to mummification, as well as fermentation mycelia in liquid culture and cultivation stromata in solid medium. Eight nucleosides and nucleobases, especially cordycepin and adenosine, were determined and analyzed with HPLC-DAD-Q-TOF-MS/MS technology. Cordycepin was detected in all forms of present O. xuefengensis strain at different contents, among which the highest content (37.1 μg/g) appeared in the stromata cultivated on solid medium. The content of adenosine in mycelia and stromata, respectively, reached 1155 μg/g and 1470 μg/g. Therefore, O. xuefengensis might be an alternative source for obtaining artificial fungus-caterpillar-larvae complex and producing cordycepin and adenosine.

BACKGROUND Lonicera macranthoides is a Chinese herb that contains a large number of bioactive spanions possessing important pharmacological activities, such as anti-tumour activity. However, detailed information about their anti-tumor activity and bioactive compounds is limited. METHODS In order to evaluate the scientific basis, the method of high-speed counter-current chromatography (HSCCC) combined with high performance liquid chromatography mass spectrometry (HPLC-ESI-QTOF/MS) has been developed to separate, purify and analyze saponins from Lonicera macranthoides. Four main saponins, Macranthoidin B (I), Macranthoidin A (II), Macranthoides B (III) and Akebia saponin D (IV) were separated by HSCCC with the solvent systems of ethyl acetate-nbutanol- water (3:2:5) and n-butanol-water-methanol-ethyl acetate (1:6:0.5:4). The purities of these four bioactive ingredients (I-IV) identified and detected by HPLC-ESI-QTOF/MS were 95.1%, 92.7%, 91.8% and 96.3%, respectively. The separated saponins were evaluated for their cytotoxic activities against six tumor cell lines (MCF-7, Hela, A549, HepG2, HT29 and Eca109). RESULTS Results show that compounds I-IV exhibited particular significant anti-tumor activities against human mammary adenocarcinoma MCF-7 cell with IC50 values ranging from 12.7 to 30.8 µM. CONCLUSION It was demonstrated that the combinative method using HPLC-ESI-QTOF/MS and HSCCC was suitable for rapid screening and isolating saponins of Lonicera macranthoides and the isolated compounds have great potential for the development of new antitumor drugs.

Purpose: To evaluate whether perioperative N-acetylcysteine (NAC) administration reduces the risk of cardiac surgery associated acute kidney injury (CSA-AKI). Materials and Methods: A systematic literature review (Medline, PubMed, Cochrane, Biomedical central, Google Scholar) identified 10 studies (1391 patients; 695 NAC and 696 placebo) that compared the efficacy and adverse effects of perioperative NAC administration for CSA-AKI prevention in adults undergoing elective cardiac surgery. Meta-analysis was performed using Comprehensive Meta-Analysis statistical software. Results: Patients in the NAC-treated and placebo groups had similar rate of CSA-AKI occurrence, change in creatinine levels, as well as the in-hospital mortality rate (RR = 0.841, 95% CI = 0.691 to 1.023, p = 0.083; pooled difference in means = −0.328, 95% CI = −0.712 to 0.056, p = 0.094; RR = 0.741, 95% CI = 0.388 to 1.418, p = 0.366, respectively). Conclusions: Our study does not support perioperative NAC administration as a mean...

As an edible sclerotia-forming fungus, Poria cocos is widely used as a food supplement and as a tonic in China. High-performance liquid chromatography-quadrupole/time-of-flight mass spectrometry (HPLC-QTOF-MS/MS) was applied to identify triterpene acids in fermented mycelia of P. cocos, as well as the epidermis and inner part of natural sclerotia. A total of 19 triterpene acids were identified in fermented mycelia, whereas 31 were identified in the epidermis and 24 in the inner part. Nine triterpene acids were quantitatively determined, and the concentrations of two valuable triterpenes, dehydropachymic acid and pachymic acid, reached 1.07 mg/g and 0.61 mg/g in the fermented mycelia part, respectively, and were both significantly higher than the concentration in the two natural parts. The fermented mycelia could be a good choice for producing some target triterpene compounds and functional foods through fermentation thanks to the high concentration of some triterpene acids.