Genus Acrostalagmus: A Prolific Producer of Natural Products.

Acrostalagmus is known for its ability to produce numerous bioactive natural products, making it valuable in drug development. This review provides information on the sources, distribution, chemical structure types, biosynthesis, and biological activities of the compounds isolated from the genus Acrostalagmus in the family Plectosphaerellaceae from 1969 to 2022. The results show that 50% of the compounds isolated from Acrostalagmus are new natural products, and 82% of the natural products derived from this genus are from the marine Acrostalagmus. The compounds isolated from Acrostalagmus exhibit diverse structures, with alkaloids being of particular importance, accounting for 56% of the natural products derived from this genus. Furthermore, within the alkaloid class, 61% belong to the epipolythiodioxopiperazine family, highlighting the significance of epipolythiodioxopiperazine as a key characteristic structure within Acrostalagmus. Seventy-two percent of natural products derived from Acrostalagmus display bioactivities, with 50% of the bioactive compounds exhibiting more significant or comparable activities than their positive controls. Interestingly, 89% of potent active compounds are derived from marine fungi, demonstrating their promising potential for development. These findings underscore Acrostalagmus, particularly the marine-derived genus Acrostalagmusas, a valuable source of new bioactive secondary metabolites, and emphasize the vast resource importance of the ocean.

New Pyrroline Isolated from Antarctic Krill-Derived Actinomycetes Nocardiopsis sp. LX-1 Combining with Molecular Networking.

Antarctic krill (Euphausia superba) of the Euphausiidae family comprise one of the largest biomasses in the world and play a key role in the Antarctic marine ecosystem. However, the study of E. superba-derived microbes and their secondary metabolites has been limited. Chemical investigation of the secondary metabolites of the actinomycetes Nocardiopsis sp. LX-1 (in the family of Nocardiopsaceae), isolated from E. superba, combined with molecular networking, led to the identification of 16 compounds a-p (purple nodes in the molecular network) and the isolation of one new pyrroline, nocarpyrroline A (1), along with 11 known compounds 2-12. The structure of the new compound 1 was elucidated by extensive spectroscopic investigation. Compound 2 exhibited broad-spectrum antibacterial activities against A. hydrophila, D. chrysanthemi, C. terrigena, X. citri pv. malvacearum and antifungal activity against C. albicans in a conventional broth dilution assay. The positive control was ciprofloxacin with the MIC values of <0.024 µM, 0.39 µM, 0.39 µM, 0.39 µM, and 0.20 µM, respectively. Compound 1 and compounds 7, 10, and 11 displayed antifungal activities against F. fujikuroi and D. citri, respectively, in modified agar diffusion test. Prochloraz was used as positive control and showed the inhibition zone radius of 17 mm and 15 mm against F. fujikuroi and D. citri, respectively. All the annotated compounds a-p by molecular networking were first discovered from the genus Nocardiopsis. Nocarpyrroline A (1) features an unprecedented 4,5-dihydro-pyrrole-2-carbonitrile substructure, and it is the first pyrroline isolated from the genus Nocardiopsis. This study further demonstrated the guiding significance of molecular networking in the research of microbial secondary metabolites.

Genome-Wide Identification and Analysis of Enhancer-Regulated microRNAs Across 31 Human Cancers.

Enhancers are cis-regulatory DNA elements that positively regulate the transcription of target genes in a tissue-specific manner, and dysregulation of target genes could lead to various diseases, such as cancer. Recent studies have shown that enhancers can regulate microRNAs (miRNAs) and participate in their biological synthesis. However, the network of enhancer-regulated miRNAs across multiple cancers is still unclear. Here, a total of 2,418 proximal enhancer-miRNA interactions and 1,280 distal enhancer-miRNA interactions were identified through the integration of genomic distance, co-expression, and 3D genome data in 31 cancers. The results showed that both proximal and distal interactions exhibited a significant cancer type-specific feature trend at the tissue level rather than at the single-cell level, and there was a noteworthy positive correlation between the expression of the miRNA and the number of enhancers regulating the same miRNA in most cancers. Furthermore, we found that there was a high correlation between the formation of enhancer-miRNA pairs and the expression of enhancer RNAs (eRNAs) whether in distal or proximal regulation. The characteristics analysis showed that miRes (enhancers that regulated miRNAs) and non-miRes presented significant differences in sequence conservation, guanine-cytosine (GC) content, and histone modification signatures. Notably, GC content, H3K4me1, and H3K36me3 were present differently between distal and proximal regulation, suggesting that they might participate in chromosome looping of enhancer-miRNA interactions. Finally, we introduced a case study, enhancer: chr1:1186391-1186507 ∼ miR-200a was highly relevant to the survival of thyroid cancer patients and a cis-eQTL SNP on the enhancer affected the expression of the TNFRSF18 gene as a tumor suppressor.

[Characteristics of Condensable Particulate Matter in Ultra-low Emission Coal-Fired Power Plants].

The condensable particle matter (CPM) from coal-fired power plants has attracted significant attention for its potential influence on air quality. The knowledge of CPM emissions from coal-fired power plants is limited. In this study, CPM was collected at the inlet and outlet of wet flue gas desulfurization (WFGD) and the outlet of wet electrostatic precipitator (WESP) using in-direct dilution method. Both mass concentration and water-soluble ions of CPM were analyzed after sampling. The gas precursors were measured at the same time. We showed that gas precursors such as HCl, HNO3, SO3, and NH3 significantly contributed to CPM from coal-fired power plants. As the temperature of flue gas decreased, these gas precursors were observed to form CPM. The major components of CPM were water-soluble ions such as SO42-, Cl-, NO3-, and NH4+. WFGD and WESP could reduce the CPM gas precursors. Therefore, CPM concentrations after WFGD and WESP of the five tested coal-fired power plants were reduced by 27% and 45%, respectively. In addition, the condensation of SO3 increased SO42- concentration but reduced Cl- and NO3- contents. Finally, SO42- was found to be the major water-soluble ion of CPM.

[Measuring the Condensable Particle Matter from a Stationary Source].

With the retrofitting of coal-fired power plants and steel plants for ultra-low-emission control, the concentration of filterable particles (FPM) from these sources is decreasing gradually. The condensable particle matter (CPM) draws more attention. The understanding of CPM emission concentration and chemical characteristics is still limited. There has been no standard determination method of CPM in China until now. In this study, three methods, including the dry impinger method (US EPA method 202), indirect dilution method, and direct dilution method, are discussed and compared in measuring CPM emissions from coal-fired power plants, coke-making plants and sintering plants. The results show that method 202 overestimates the emissions of CPM, due to the fact that the gaseous HCl or SO2 dissolves into condensable liquid and cannot be completely eliminated by N2 purging after sampling. Instead, CPM measured using the indirect dilution method better represents its real emission levels into the atmosphere.

Decreased PKG transcription mediated by PI3K/Akt/FoxO1 pathway is involved in the development of nitroglycerin tolerance.

Phosphoinositide 3-kinase (PI3K)/Akt plays a pivotal role in the vascular response. The present study is to determine whether PI3K/Akt pathway in vascular smooth muscle cells is involved in nitroglycerin (NTG) tolerance and the underlying mechanism. Nitrate tolerance of porcine coronary arteries in vitro was induced by incubation of NTG (10-5 M) for 24 h. Nitrate tolerance in vivo was obtained by subcutaneous injection of mice with NTG (20 mg kg-1, tid, 3 days) and the aortas were used. Protein levels of total and phosphorylated Akt, forkhead box protein O1 (FoxO1), and cGMP-dependent protein kinase (PKG) were determined by western blot analysis. Isometric vessel tension was recorded by organ chamber technique. PKG mRNA was determined by real-time PCR. The cellular translocation of FoxO1 was observed by immunofluorescence. Reactive oxygen species (ROS) level was measured by DHE staining. The vascular relaxation to NTG was significantly inhibited in in vivo and in vitro NTG tolerant arteries. Meanwhile, the protein level of phosphorylated Akt at Ser473 was increased in the tolerant arteries. The attenuated relaxation and the augmented Akt-p were ameliorated by LY294002, a specific inhibitor of PI3K. The protein and mRNA expression of PKG were significantly down-regulated in NTG tolerant arteries, which were reversed by LY294002. The level of phosphorylated FoxO1 at Ser256 and its translocation from the nucleus to the cytosol were both increased in NTG tolerance and were also inhibited by LY294002. ROS production was significantly increased in NTG tolerant arteries, which was not be affected by LY294002 but inhibited by N-acetyl-L-cysteine. In conclusion, the present study suggests that PI3K/Akt in vascular smooth muscle is involved in the development of NTG tolerance via inhibiting PKG transcription and the effect is mediated by FoxO1.

Predictive role of UCA1-containing exosomes in cetuximab-resistant colorectal cancer.

BACKGROUND: Primary or acquired resistance to cetuximab often occurs during targeted therapy in metastatic colorectal cancer (mCRC) patients. In many cancers, the key role of the long noncoding RNA (lncRNA) urothelial carcinoma-associated 1 (UCA1) in anticancer drug resistance has been confirmed. Emerging evidence has shown that specific exosomal lncRNAs may serve as meaningful biomarkers. In this study, we hypothesize that exosomal UCA1 might predict the response to cetuximab in CRC patients. METHODS: First, acquired cetuximab-resistant cell lines were generated, and UCA1 expressions in these cells and their exosomes were compared. We also systematically evaluate the stability of exosomal UCA1. Thereafter, the predictive value of exosomal UCA1 in CRC patients treated with cetuximab was evaluated. Finally, through cell apoptosis assays and immunofluorescence staining, we analyzed the role of UCA1-containing exosomes in conferring cetuximab resistance. RESULTS: UCA1 expression was markedly higher in cetuximab-resistant cancer cells and their exosomes. Exosomal UCA1 was shown to be detectable and stable in serum from CRC patients. In addition, circulating UCA1-containing exosomes could predict the clinical outcome of cetuximab therapy in CRC patients, and UCA1 expression was considerably higher in the progressive disease/stable disease patients than in the partial response/complete response patients. Furthermore, exosomes derived from cetuximab-resistant cells could alter UCA1 expression and transmit cetuximab resistance to sensitive cells. CONCLUSIONS: We discovered a novel role of UCA1-containing exosomes, showed their capability to transmit drug resistance and investigated their potential clinical use in predicting cetuximab resistance.

Pharmacokinetics of the prototype and hydrolyzed carboxylic forms of ginkgolides A, B, and K administered as a ginkgo diterpene lactones meglumine injection in beagle dogs.

Ginkgo diterpene lactones meglumine injection (GDLI) is a commercially available product used for neuroprotection. However, the pharmacokinetic properties of the prototypes and hydrolyzed carboxylic forms of the primary components in GDLI, i.e., ginkgolide A (GA), ginkgolide B (GB), and ginkgolide K (GK), have never been fully evaluated in beagle dogs. In this work, a simple, sensitive, and reliable method based on ultra-fast liquid chromatography-tandem mass spectrometry (UFLC-MS/MS) was developed, and the prototypes and total amounts of GA, GB, and GK were determined in beagle dog plasma. The plasma concentrations of the hydrolyzed carboxylic forms were calculated by subtracting the prototype concentrations from the total lactone concentrations. For the first time, the pharmacokinetics of GA, GB, and GK were fully assessed in three forms, i.e., the prototypes, the hydrolyzed carboxylic forms, and the total amounts, after intravenous administration of GDLI in beagle dogs. It was shown that ginkgolides primarily existed in the hydrolyzed form in plasma, and the ratio of hydrolysates to prototype forms of GA and GB decreased gradually to a homeostatic ratio. All of the three forms of the three ginkgolides showed linear exposure of AUC to the dosages. GA, GB, and GK showed a constant half-life approximately 2.7, 3.4, and 1.2 h, respectively, which were consistent for the forms at three dose levels (0.3, 1.0, and 3.0 mg·kg-1) and after a consecutive injection of GDLI for 7 days (1.0 mg·kg-1).

siRNA-mediated inactivation of HER3 improves the antitumour activity and sensitivity of gefitinib in gastric cancer cells.

The human EGFR family consists of four type-1 transmembrane tyrosine kinase receptors: HER1 (EGFR, ErbB1), HER2 (Neu, ErbB2), HER3 (ErbB3), and HER4 (ErbB4). HER3 can dimerize with EGFR, HER2 and even c-Met and likely plays a central role in the response to EGFR-targeted therapy. Because HER3 lacks significant kinase activity and cannot be inhibited by tyrosine kinase inhibitors, neutralizing antibodies and alternative inhibitors of HER3 have been sought as cancer therapeutics. Here, we describe the stable suppression of HER3 mRNA and protein using siRNA. The inhibition of HER3 expression decreased cell proliferation, suppressed cell cycle progression, induced apoptosis and inhibited cell motility, migration, invasiveness, and soft agar growth. In addition, we found that gefitinib treatment increased the HER3 and HER2 mRNA levels. The administration of various concentrations of gefitinib to HER3-knockdown cells enhanced antitumour activity and sensitivity due to the downregulation of protein phosphorylation via PI3K/AKT and ERK signalling. Our results support the use of combined treatments targeting multiple EGFR receptors, particularly the use of HER3 inhibitors combined with EGFR inhibitors, such as gefitinib.

Potential therapeutic effect of epigenetic therapy on treatment-induced neuroendocrine prostate cancer.

Although adenocarcinomas of the prostate are relatively indolent, some patients with advanced adenocarcinomas show recurrence of treatment-induced neuroendocrine prostate cancer, which is highly aggressive and lethal. Detailed biological features of treatment-induced neuroendocrine prostate cancer have not been characterized owing to limited biopsies/resections and the lack of a cellular model. In this study, we used a unique cellular model (LNCaP/NE1.8) to investigate the potential role of cancer stem cells in treatment-induced neuroendocrine prostate cancer with acquired resistance to hormonal therapy and chemotherapy. We also studied the role of cancer stem cells in enhancing invasion in treatment-induced neuroendocrine prostate cancer cells that recurred after long-term androgen-ablation treatment. Using an in vitro system mimicking clinical androgen-ablation, our results showed that the neuroendocrine-like subclone NE1.8 cells were enriched with cancer stem cells. Compared to parental prostate adenocarcinoma LNCaP cells, NE1.8 cells are more resistant to androgen deprivation therapy and chemotherapeutic agents and show increased cancer cell invasiveness. Results from this study also suggest a potential epigenetic therapeutic strategy using suberoylanilide hydroxamic acid, a histone deacetylase inhibitor, as a chemotherapeutic agent for therapy-resistant treatment-induced neuroendocrine prostate cancer cells to minimize the risk of prostate cancer recurrence and metastasis.

Qualitative and quantitative analysis of major constituents from Dazhu Hongjingtian capsule by UPLC/Q-TOF-MS/MS combined with UPLC/QQQ-MS/MS.

In this work, a sensitive and efficient method was established and validated for qualitative and quantitative analysis of major bioactive constituents in Dazhu Hongjingtian capsule by liquid chromatography tandem mass spectrometry. A total of 32 compounds were tentatively identified using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Furthermore, 12 constituents, namely gallic acid, 3,4-dihydroxybenzoic acid, salidroside, p-coumaric acid-4-O-ß-d-glucopyranoside, bergeninum, 4-hydroxybenzoic acid, 4-hydroxyphenylacetic acid, syringate, 6''-O-galloylsalidroside, rhodiosin, rhodionin and kaempferol-7-O-α-l-rhamnoside, were simultaneously quantified by the developed ultra-performance liquid chromatography coupled with a triple quadrupole mass spectrometry method in 9 min. All of them were analyzed on an Agilent ZorBax SB-C18 column (3.0 × 100 mm, 1.8 µm) with linear gradient elution of methanol-0.1% formic acid water. The proposed method was applied to analyze three batches of samples with acceptable linearity (R, 0.9979-0.9997), precision (RSD, 1.3-4.7%), repeatability (RSD, 1.7-4.9%), stability (RSD, 2.2-4.9%) and recovery (RSD, 0.6-4.4%) of the 12 compounds. As a result, the analytical method possessing high throughput and sensitivity is suitable for the quality control of Dazhu Hongjingtian capsule.

Impact of parameter fluctuations on the performance of ethanol precipitation in production of Re Du Ning Injections, based on HPLC fingerprints and principal component analysis.

The present study was designed to determine the relationships between the performance of ethanol precipitation and seven process parameters in the ethanol precipitation process of Re Du Ning Injections, including concentrate density, concentrate temperature, ethanol content, flow rate and stir rate in the addition of ethanol, precipitation time, and precipitation temperature. Under the experimental and simulated production conditions, a series of precipitated resultants were prepared by changing these variables one by one, and then examined by HPLC fingerprint analyses. Different from the traditional evaluation model based on single or a few constituents, the fingerprint data of every parameter fluctuation test was processed with Principal Component Analysis (PCA) to comprehensively assess the performance of ethanol precipitation. Our results showed that concentrate density, ethanol content, and precipitation time were the most important parameters that influence the recovery of active compounds in precipitation resultants. The present study would provide some reference for pharmaceutical scientists engaged in research on pharmaceutical process optimization and help pharmaceutical enterprises adapt a scientific and reasonable cost-effective approach to ensure the batch-to-batch quality consistency of the final products.

Research on the change of chemical composition in productive process of Re Du Ning injection by HPLC/Q-TOF MS.

A high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (HPLC/Q-TOF MS) was developed for the analysis of chemical composition change in the production process of Re Du Ning injection, a Chinese medicine preparation with a combination of Lonicera japonica Thunb., Gardenia jasminoides Ellis and Artemisia annua L. A total of 90 compounds from raw materials-intermediates-Re Du Ning injection were detected; among them, 55 compounds were identified or tentatively characterized, and the characteristic ions of different types of compounds were described. Based on these studies, the different types of compounds in the various process routes were analyzed. A total of 28 compounds, including seven iridoid glycosides and six monoterpenes from G. jasminoides Ellis, five iridoid glycosides, nine phenolic acids and one unknown compound from L. japonica Thunb., were transferred to Re Du Ning injection, and two unknown compounds were generated in the production process of Re Du Ning injection. The results indicated that the Chinese Medicine Pharmaceutical process control is very important. This method could provide some reference for other Chinese medicine preparations.

[Metabolism of six saponins by rat intestinal bacteria in vitro].

To investigate the metabolism of six saponins by rat intestinal bacteria in vitro.Six saponins, including notoginsenoside R1, ginsenoside Rg1, ginsenoside Rg2, ginsenoside Re, ginsenoside Rd and ginsenoside Rb1, were incubated for 8 and 24 h with rat intestinal bacteria under anaerobic environment, respectively. After the samples were precipitated by acetonitrile and extracted with ethyl acetate, LC-Q-TOF-MS/MS was applied for the qualitative analysis of the metabolites. The potential metabolites in rat feces were analyzed by comparing the total ion current of the test samples and blank samples and analyzing the quasi-molecular ion and fragment ion of all chromatograms. The results showed that six saponins could be easily metabolized by rat intestinal bacteria. Notoginsenoside R1 was mainly metabolized into five metabolites, and it's metabolic pathway was notoginsenoside R1→ginsenoside Rg1→ginsenoside Rh1 and ginsenoside F1→protopanaxatriol→dehydrogenated protopanaxatriol. Ginsenoside Rg1 was mainly metabolized into four metabolites, and it's metabolic pathway was ginsenoside Rg1→ginsenoside Rh1 and ginsenoside F1→protopanaxatriol→dehydrogenated protopanaxatriol. Ginsenoside Rg2 was mainly metabolized into two metabolites, and it's metabolic pathway was ginsenoside Rg2→ protopanaxatriol→dehydrogenated protopanaxatriol. Ginsenoside Re was mainly metabolized into four metabolites, and it's metabolic pathway was ginsenoside Re→ginsenoside Rg2→ginsenoside F1→protopanaxatriol→dehydrogenated protopanaxatriol. Ginsenoside Rd was mainly metabolized into four metabolites, and it's metabolic pathway was ginsenoside Rd→ginsenoside Rg3 and ginsenoside F2→ginsenoside Rh2→protopanaxadiol. Ginsenoside Rb1 was mainly metabolized into five metabolites, and it's metabolic pathway was ginsenoside Rb1→ginsenoside Rd→ginsenoside Rg3 and ginsenoside F2→ginsenoside Rh2→protopanaxadiol. In summary, six saponins could be quickly metabolized by rat intestinal bacteria in vitro. Their major metabolic pathways were deglycosylation and dehydrogenation.

[Determination of five kinds of trace ginkgolic acids in diterpene ginkgolides meglumine injection materials by LC-MS/MS].

To develop a LC-MS/MS method for the determination of five kinds of trace ginkgolic acids in diterpene ginkgolides meglumine injection materials, the column was Agilent ZORBAX Eclipse plus C18 (3.0 mm x 50 mm, 1.8 µm), and the mobile phase consisted of methanol-water (containing 0.2% formic acid) (95:5) at a flow rate of 0.5 mL · min(-1). The multiple reaction ion monitoring (MRM) with an ESI interface in the negative ion mode was selected. The results showed that the linear ranges of five kinds of ginkgolic acids were in the range of 0.2-36.0 µg · L(-1) (r ≥ 0.999 5). The lowest limit of quantification (LOQ) of ginkgo acid C13: 0, C15:1, C17:2, C15:0 and C17:1 were 0.18, 0.18, 0.21, 0.10 and 0.20 µg · L(-1), respectively. The average recovery was between 73.28% and 87.56%, and the average content of total ginkgolic acids in three batches of samples was in the range of 0.023-0.028 µg · g(-1), which was much lower than 2 µg · g(-1) prescribed in drug registration standards. This method is simple and rapid with high sensitivity, which can be used for the determination of five kinds of trace ginkgolic acids in diterpene ginkgolides meglumine injection materials.

[Quantitative and qualitative evaluation on tablets of Ginkgo biloba leaves using fingerprint and LC-MS analysis].

A reasonable method for the quality control of tablets of Ginkgo biloba leaves was established in this paper. The total flavonol glycosides and terpene lactones of G. biloba tablets were quantified by HPLC. Totally, 16 batches of the commercially available tablets of G. biloba leaves were determined. Among of them, 2 batches were unqualified in the content of total flavonol glycosides, and 3 batches were unqualified in the content of terpene lactones. A validated HPLC fingerprint method was established to evaluate the commercially available tablets of G. biloba leaves with the assistance of LC-MS. Sixteen batches showed the similarity of 0.763-0.989. There were 31 fingerprint chromatogram peaks were identified as flavonoids compositions by LC-MS. This provides a research idea for the quality control of tablets of G. biloba leaves.

[Similarity between leaves of Nauclea officinalis and stems of Nauclea officinalis].

The study is to develop a method to determine 3 batches leaves of Nauclea officinalis and stems of N. officinalis by HPLC. The differences between strictosamide contents and fingerprints was compared, then chromatographic peak of fingerprints was validated with the assistance of LC-MS. The strictosamide contents in stems of N. officinalis were higher than leaves of N. officinalis. The main chemical composition in leaves of N. officinalis and stems of N. officinalis were alkaloid which revealed by LC-MS. There are 7 chemical compositions were same between them, but the chemical composition in leaves of N. officinalis is more than stems of N. officinalis. This provides a scientific basis for the development of the potential medicinal value of leaves of N. officinalis and the sustainable utilization of N. officinalis.

[Study on limit detection of flavones in diterpene ginkgolides meglumine injection materials by LC-MS and HPLC-DAD].

Limit test of flavones in diterpene ginkgolides meglumine injection materials by UV-Vis and HPLC-DAD method was studied in this essay. The HPLC-DAD method has lower LOD (about 1% of the UV-Vis), that is, the sensitivity is higher than UV-Vis method. Through the analysis of the kinds of flavonoids ingredients in the samples by LC-MS, the three compounds with highest contents are kaempferol, quercetin and isorhamnetin. Kaempferol, quercetin and isorhamnetin were chosen as reference compounds for HPLC analysis, and the HPLC separation analysis was carried on an Agilent Eclipse plus C18 column (4.6 mm x 250 mm, 5 µm) with methanol and water containing 0.4% phosphoric acid (50: 50) as mobile phase, and the flow rate was 1.0 mL x min(-1). The detection wavelength was set at 360 nm. This method has good specificity, precision and reproducibility. The LODs of quercetin, kaempferide and isorhamnetin were 27.6, 22.3, 29.5 µg x L(-1). The average recovery was 87.9% (RSD 3.3%), 91.7% (RSD 3.1%), 88.3 (RSD 1.3%) for quercetin, kaempferide and isorhamnetin, respectively. Based on the 10 batches of sample results and sensitivity of different HPLC, the content of total flavonoids ingredients of diterpene ginkgolides meglumine injection materials was limited no more than 2 x 10(-5). This method is simple, quick and has good maneuverability, and could be used to the limit test of flavonoids in the diterpene ginkgolides meglumine injection materials.

Sonodynamically induced anti-tumor effect of 5-aminolevulinic acid on pancreatic cancer cells.

Sonodynamic therapy (SDT), a promising modality for cancer treatment, involves the synergistic interaction of ultrasound and some chemical compounds termed sonosensitizers. However, its effect on pancreatic cancer cells remains unclear. In our study, we sought to identify the cytotoxic effects of ultrasound-activated 5-aminolevulinic acid on human pancreatic cancer Capan-1 cells. Cell viability was determined by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide) analysis; mitochondrial membrane potential was assessed using the fluorescent probe jc-1; apoptosis was evaluated by flow cytometry; cell morphology was investigated by scanning electron microscopy; apoptosis-related protein expression was analyzed by Western blot assay. We found that SDT significantly decreased the survival rate of cells, and this effect increased with 5-aminolevulinic acid concentration and ultrasound exposure time. The mechanism underlying the effect of SDT involves, in part, the induction of a conspicuous loss in mitochondrial membrane potential and, in part, the induction of apoptosis through upregulation of Bax expression, downregulation of Bcl-2 and increased activation of procaspase-3. These results indicate that the ultrasonically induced cell killing effect could be enhanced by 5-ALA and that the mitochondrial pathway might be involved in the cell damage process. We conclude that SDT is a promising new methodology for pancreatic cancer treatment.