bluuebunny/crossref_metadata_2025_split huggingface dataset:
Polyphenolic Content and Anti‐oxidation activity in Annona fruit and its Effects on Lymphoma Cancer Cells Proliferation
Authors: AlShaya Huda , Li Haiwen , Hamama Anwar , Siddiqui Rafat A 
Published: June 2021

IntroductionLymphoma is a cancer of the lymph nodes and lymphatic system. The two main types are Hodgkin and non‐Hodgkin. Non‐Hodgkin lymphoma is the most common. The lymphomas can be effectively treated with chemotherapy; however, the treatments have severe side effects that can be permanent. Studies have shown a relationship between a high intake of vegetables/fruits and reduced risk of cancer development, including lymphomas.HypothesisWe hypothesize that Annona fruit, which is rich in fibers and phytochemicals, can be very effective in inhibiting lymphoma cancer growth.ExperimentalThe skin, pulp and seeds fractions of Annona fruits were extracted into water, methanol or chloroform and then assayed for their total phenolic contents and anti‐oxidation activities and then tested for cell proliferation inhibitory activity using Ramos‐1 lymphoma cell line.ResultsThe highest concentration of total phenols was present in the skin fraction; however, the pulp has the highest total amounts. The methanol fractions of skin and pulp and water extract of seeds contained the highest anti‐oxidation activity. The methanol extracts of skin, pulp and seeds have moderate whereas chloroform extracts of pulp and seeds have strong inhibition of Ramos‐1 lymphoma cell proliferation.ConclusionsThe edible pulp of Annona fruits can provide phenolic anti‐oxidants which can also be effective in preventing/treating lymphoma. The skin and seeds are non‐edible but can be used to isolate potent compounds with potential anti‐cancer activity.Future DirectionsStudies are required to isolate and identify the active compounds from Annona fruit and to test them in an animal model.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Binding of Telomeric DNA G‐Quadruplexes by Abietane Diterpene Natural Products
Authors: Kanlong Joseph , McKnight Ruel 
Published: June 2021

We have carried out studies on a homologous series of abietane diterpenes binding to a human telomeric G‐quadruplex (G4) DNA sequence [5′G3(T2AG3)3]. These G4 DNA structures are found in G‐rich telomeric regions at the ends of chromosomes and near promoter regions of oncogenes. Targeted stabilization of G‐quadruplex DNA by drugs has been implicated in telomerase inhibition and downregulation of oncogenes, both of which should result in an inhibition of cancer growth. The abietane diterpenes are a class of natural products isolated from certain plants (e.g., Hyptis verticillata) known in many cultures for their anti‐microbial, anti‐inflammatory, and anti‐cancer medicinal benefits. Binding characteristics were evaluated using circular dichroism (CD) spectroscopy, UV‐thermal denaturation, and fluorescence displacement studies. Overall, our studies show that the abietane diterpenes of this study bind to human telomeric G4 DNA, with selected compounds binding strongly. CD spectra indicate that these compounds interact with G4 DNA, either via the G4 DNA groove or by base stacking. For one compound in particular, we observed a pair of strong induced CD signals (300 – 400 nm) associated with changes in the drug environment as it binds DNA. We also observe strong positive signals around the 250 and 285 nm absorption bands of the diterpenes. These suggest the involvement of stacking interactions with the DNA bases or within the DNA grooves. Several of the abietane diterpenes bind to DNA, resulting in increased thermal stability suggesting that binding of our compounds results in G4 stabilization (ΔTm = 7°C). Thioflavin‐T (a fluorescent dye known to bind to G4 DNA) was used for fluorescent displacement studies and indicated that some diterpenes were unable to displace it from its binding site on the G4 DNA, suggesting the diterpenes occupied distinct binding sites. The binding of these abietane diterpenes to G4 DNA suggests promising therapeutic potential as lead compounds and warrants further investigation.Support or Funding InformationThis study was lead by Dr Ruel Mcknight, professor of Chemistry and Biochemistry at SUNY Geneseo.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Sphingomyelin synthase inhibition in sarcomas results in ceramide accumulation and apoptosis
Authors: Pavek Adriene , Afrin Farjana , Meldrum Trevor , Pashikanti Srinath , Barrott Jared 
Published: June 2021

Sphingolipid metabolism is critical to cellular homeostasis especially as cells undergo mitosis. It is, therefore, unsurprising that the sphingolipid pathway is upregulated in a number of a cancers. Sphingoid bases such as sphingosine and ceramide are rapidly synthesized to provide the building blocks of other sphingolipids. Inhibition of downstream enzymes that convert sphingosine and ceramide into sphingolipids can lead to an increase of ceramide, which results in cellular toxicity and initiation of apoptosis. Using the marine natural product Jaspine B and chemically synthesized analogues, we investigated the potency of inhibiting sphingomyelin synthase in sarcoma cell lines. Sphingomyelin synthase is a downstream enzyme that converts ceramide into sphingomyelin by adding the polar head group phosphorylcholine to ceramide. Jaspine B and its analogues exhibited submicromolar potency against several human sarcoma cell lines. It was determined that the inhibition of sphingomyelin synthase resulted in an increase in ceramide and sphingosine levels and that sphingomyelinase enzymatic activity increased. While the mitochondria mass remained the same, the membrane potential of the mitochondria was significantly affected by the presence of the inhibitors. In conclusion, inhibitors of sphingolipid metabolism are viable therapeutic options with high untapped potential.Support or Funding InformationIdaho State University Start UpThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Natural Lignan Justicidin A‐Enhanced Mitophagy and Mitogenesis in Cytotoxicity of Grade III Human Bladder Cancer Cells
Authors: Su Chun‐Li , Chang Kai‐Hsun 
Published: June 2021

Mitochondria are crucial organelles for energy metabolism, cell signaling, and apoptosis in mammalian cells. To maintain cellular homeostasis, the cell has evolved complex systems for the quality control of mitochondria. Justicidin A (JA) is a novel and structure‐defined arylnaphthalide lignan isolated from Justicia procumbens, which has been used as an herbal remedy in Taiwan and China for fever, cancer, and pain. Our previous reports show that JA suppressed the growth of human hepatocellular carcinoma Hep 3B and human colorectal cancer HT‐29 cells in NOD‐SCID mice, and the JA‐induced cytotoxicity was observed via induction of autophagy and mitochondrion‐related apoptosis. JA also preferentially inhibited the population growth of many other cancer cell types including grade III human bladder cancer T24 cells, compared to that of normal human peripheral blood mononuclear cells (PBMC). The 50% population growth inhibition of JA for PBMC was at least 1000‐fold higher than that for T24 cells. In the present study, we reveal that JA‐induced autophagy in T24 cells, characterized by increases in LC3‐II expression and acidic vesicular organelles formation, was paralleled by inhibition of mTOR, production of Atg5‐Atg12 complex, and activation of MEK/ERK. The JA‐triggered alternation of mitochondrial membrane potential, determined by staining with rhodamin123 followed by flow cytometry, in combined with the occurrence of autophagy implies the degradation of damaged mitochondria by a form of selective autophagy (mitophagy). Elevation of phospho‐Parkin and BNIP3 expressions by Western and co‐localization of BNIP3 and LC3 puncta by confocal microscopy indicate that the JA‐induced mitophagy proceeded via the Parkin‐ and BNIP3‐related pathways. Since mitophagy is balanced by mitochondrial biogenesis for generation of new mitochondria (mitogenesis), the increase in the intensity of Mito‐Tracker deep red and nonyl acridine orange as well as upregulation of mitochondrial UQCRC1 and COXIV protein expressions reveal the induction of mitogenesis in JA‐treated cells. Nevertheless, co‐administration of JA enhanced cytotoxicity of T24 cells to a combination of cisplatin and gemcitabine, the standard first‐line treatment for patients with locally advanced and metastatic bladder cancer, and produced a synergistic effect. Overall, our data indicate a possible role of mitophagy and mitogenesis in JA‐induced cytotoxicity of bladder cancer cells.Support or Funding InformationSupported in part by the Ministry of Science and Technology, Taiwan, No. MOST 105‐2320‐B‐003‐003 and 106‐2320‐B‐003‐006‐MY3This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Secondary structure analysis of intramolecular DNA four‐way junction composed of phosphorothioate bonds
Authors: Troisi Maria , Parker Elliot , Klein Mitchell , Moorhead Gaston , Alvarado Alice , Herrada Hector , Ghebreigziabher Daniel , Shur Courtney , Bell Anthony Jerome 
Published: June 2021

Research shows that cruciform and bent DNA can target the DNA‐binding cytokine, High Mobility Group B1 (HMGB1). HMGB1 was initially classified as a highly abundant architectural nuclear protein. It is now clear that HMGB1 also functions as a damage associated molecular pattern molecule (DAMP). And several studies link deleterious HMGB1 proinflammatory signaling with an array of diseases and immune disorders such as: atherosclerosis, cystic fibrosis, lupus and sepsis. Hence, HMGB1 garners a great deal of attention as a disease biomarker and therapeutic target. We hypothesize that immobilized DNA four‐way junctions (4WJs) can target HMGB1. To enhance the stability of 4WJs for ex vivo studies, the helical termini are modified to generate intramolecular constructs. Phosphorothioate (PS) bonds are inserted into the intramolecular junction lattice to enhance nuclease resistance. In this study, the secondary structure of five intramolecular 4WJs are investigated vs. the DNA control, J1. J1 is an immobilized 4WJ that is composed of four asymmetric strands of DNA. Circular dichroism (CD) studies show that the secondary structure of each intramolecular 4WJ (DNA and PS constructs) is composed of B‐ and A‐form helices. Whereas, the DNA control J1 is devoid of A‐form helices. The melting temperature (Tm) of each intramolecular 4WJ is significantly higher than J1. The Tm values for the intramolecular 4WJs are 25° – 30°C higher than J1. Electrophoretic mobility shift assays show that HMG proteins bind intramolecular 4WJs with similar affinity to J1. The data clearly shows that the lattice of an immobilized DNA 4WJ can be redesigned to enhance conformational stability and maintain: i) native secondary structure and ii) HMG binding affinity.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Yiqi‐Huoxue Granule ameliorates the apoptosis induced by hydrogen peroxide through modulating UCP2 in H9c2 cells
Authors: WU HONG 
Published: June 2021

The conservation of Yiqi‐Huoxue Granule (YQHX) on patients with cardiovascular diseases is associated with the alleviation of oxidative stress‐mediated injury; however, the underlying mechanism(s) is unclear. Our purpose was to explore the protective effects of YQHX on apoptosis induced by hydrogen peroxide (H2O2) in H9c2 cells. H9c2 cells were pretreated with YQHX for 16 h before being exposed to 200 μM H2O2 for 6 h. The apoptosis induced by H2O2 was determined using hoechst 33342 staining and Annexin‐V FITC/PI method. The expression level of UCP2, Bcl‐2, Bax, and caspase‐3 were measured using Western blotting. The effects of UCP2 knockdown with Lenti‐shUCP2 vector on cell apoptosis and production of intracellular ROS were also explored. H2O2 stimulation resulted in prominent activation of oxidative stress followed by enhanced apoptosis and ROS production, as well as decreased UCP2 expression. YQHX at the concentration of 0.75 or 1.5 mg/ml significantly decreased the expression of Bax and caspase‐3, whereas increased the expression of Bcl‐2 and UCP2. The above effects were weakened by transgenic UCP2 knockdown. In short, the present study suggested that YQHX ameliorates the apoptosis induced by H2O2 through modulating the expression of UCP in H9c2 Cells, indicating that YQHX is a potential therapeutic medication for the treatment of I/R injury‐mediated apoptosis.Support or Funding InformationThe present work was supported by grants from the National Natural Science Foundation of China (No. 81473453, 81673800) and the Science and Technology Innovation Talents in Universities of Henan Province (No. 14HASTIT028).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Wenyang‐Yiqi Granule inhibits OGD‐induced autophagy by activating mTOR pathway
Authors: Yu Xiaofang , Wu Hong , Han Lihua , Wang Zhentao 
Published: June 2021

Our aim is to explore the effects of Wenyang‐Yiqi Granule (WYYQ) on autophagy induced by oxygen glucose deprivation (OGD) in H9c2 cells. The cultured H9c2 cells were divided into control group, OGD group, Rapamycin group, WYYQ group, and WYYQ plus Rapamycin group. The cells in each treatment group were exposed to OGD for 6 h. The mRNA expression of Beclin‐1 and microtubule‐associated protein light chain 3 (LC3) was assessed using real‐time PCR. The expression of Beclin‐1, p62, LC3‐II/LC3‐I ratio, and the phosphorylation of mTOR pathway were detected using Western bolt. The apoptosis was measured using flow cytometry. The results showed that the expression of Beclin‐1 and LC3 increased whereas the expression of P62 decreased in OGD‐treated H9c2 cells. WYYQ significantly inhibited the expression of Beclin‐1 and LC3 and increased the expression of P62 at mRNA and protein level. The phosphorylation of mTOR pathway was suppressed in OGD condition, and WYYQ enhanced the phosphorylation of mTOR pathway. Rapamycin, an mTOR inhibitor, abrogated the upregulation of mTOR phosphorylation by WYYQ, however, it did not abolish the downregulation of autophagy‐related genes and proteins by WYYQ under OGD condition. Taken together, WYYQ ameliorates OGD‐induced autophagy, relating to its activation of mTOR signaling pathway.Support or Funding InformationThis work was financially supported by grants from the National Natural Science Foundation of China (No. 81373610).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Utilization of 31P NMR and ITC to Study the Binding of ATP, ADP, and AMP with Metal Ions
Authors: Zea Corbin , Donels Jordan , Greenwood Brandon , Akers Isabell , Thomsen Alli , Limani Arijan , Kanne Dillon 
Published: June 2021

Magnesium is known to be an important cofactor in many enzymatic processes involving adenosine triphosphate (ATP), adenosine diphosphate (ADP), and adenosine monophosphate (AMP). The binding of magnesium to the phosphate end of the nucleotide phosphate is well known and crucial to the catalytic activity of many enzymatic reactions. There is high selectivity for magnesium and other metals are not found to participate in the binding and enzymatic catalysis of nucleotide phosphates. We aim to study the binding of various metals in addition to magnesium to see if it can be determined why other metals are not as crucial to enzymatic binding. To answer this question we assessed metal ion binding to ATP, ADP, and AMP in pH 6.9 and 8.0 HEPES buffer using 31P Nuclear Magnetic Resonance (NMR) as well as Isothermal Titration Calorimetry (ITC). These measurements will correlate the conformational changes seen in the 31P NMR to the binding energy measured in ITC. With magnesium we see increasing conformational changes in the 31P NMR that correlate with a large binding energy seen in ITC. With other metal ions we do see a conformational change in the NMR but the binding energy is not as large as that found for magnesium.Support or Funding InformationInstrumentation support was provided by the Carver Foundation and the R.W. and Mary Nelson FoundationThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Kangxian‐Yixin shortens the duration of paroxysmal atrial fibrillation in rats
Authors: Dong Lisha , Wang Zhentao , Chang Hongbo , Wu Hong 
Published: June 2021

Our aim is to observe the effects of Kangxian‐Yixin concentrated pill (KXYX) on the duration of atrial fibrillation in rats with paroxysmal atrial fibrillation. Rat models of paroxysmal atrial fibrillation were induced by tail vein injection of acetylcholine as well as calcium chloride. Fifty male Wistar rats were randomly divided into model group, propranolol group and KXYX groups in high, medium and low dose. The model group was administered of saline in equal volume, while the other groups were given the corresponding dose of medicines one time a day for 1 week. After 7 days, the rat model of paroxysmal atrial fibrillation was generated and used to record the duration of atrial fibrillation. Compared with the model group, the duration of atrial fibrillation in treatment groups were significantly shortened (P<0.01 or P<0.05). And compared with the propranolol group, the duration in the medium‐dose and low‐dose KXYX groups were markedly longer (P<0.01 or P<0.05). The duration in the high and medium‐dose groups were shorter than that in the low‐dose KXYX group (P<0.01 or P<0.05). Taken together, KXYX shortens the duration of paroxysmal atrial fibrillation, suggesting that it may be a promising therapeutic medication for intervention of paroxysmal atrial fibrillation.Support or Funding InformationThis work was supported by grant from the National Natural Science Foundation of China (No. 81573920).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Specific Photocleavage Activity of N‐Methylmesoporphyrin IX on G‐Quadruplex DNA Structures
Authors: Escobedo Ruby A , Long Kimberly J , McBrayer Dominic N , Schoonover Michelle , Kerwin Sean M 
Published: June 2021

G‐rich regions, at which G‐quadruplexes (G4) are proposed to form, are associated with promoter regions within proto‐oncogenes and may play a role in cell proliferation and carcinogenesis. The ability to identify the formation of G4 structures in these regions, including the temporal aspects of G‐quadruplex formation, is essential to establish the role of these structures in transcriptional regulation. We have focused on identifying highly selective G4 photocleavage agents as molecular probes for establishing the location and timing of G4 formation. N‐methylmesoporphyrin IX (NMM) has long been known as a G4 ligand; however, there has been little investigation into its DNA photocleavage activity. Here we report the ability of NMM to act as a highly selective photocleavage agent for specific G4 structures. We first studied the interaction of NMM with the G4 structures formed by DNA oligonucleotides containing the c‐MYC promoter or human telomeric (hTel) sequences formed in the presence of either Na+ or K+‐containing buffers using a FRET‐based Tm assay and CD spectroscopy. We employed a fluorescence‐based solution assay for G4 cleavage to establish that NMM effects photocleavage (420 nm) of c‐MYC more efficiently than the hTel G4 under both Na+ and K+ conditions, and effects photocleavage of c‐MYC G4 even under white light irradiation. Using denaturing polyacrylamide gel electrophoresis (PAGE), we confirmed this selective photocleavage and demonstrate that cleavage occurs at specific guanine residues of the c‐MYC G4. In order to determine if the photocleavage proceeds through the generation of reactive oxygen species like singlet oxygen, we carried out photocleavage reactions in the presence of H2O and D2O, and employed a turn‐on fluorescent singlet oxygen sensor to detect 1O2 generation. We find that NMM acts to destabilize specific G4 topologies, but oligonucleotides annealed in the presence of NMM form alternative topologies that are thermally stabilized. NMM photocleavage is highly selective for G4 DNA versus duplex DNA, and the K+‐stabilized c‐MYC G4 is preferentially cleaved compared to the Na+‐stabilized structure and the hTel G4 in either Na+ or K+. PAGE analysis indicates that NMM photocleavage of c‐MYC G4 occurs preferentially at the 3′ G‐tetrad residues. This photocleavage does not appear to be due to 1O2. These results indicate that NMM may be a useful tool for elucidating the role of promoter G‐quadruplex structures.Support or Funding InformationSupport for this work by the Cancer Prevention and Research Institute of Texas (RP160852) and Texas State University is gratefully acknowledged.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Anticancer Effect of Curcumin‐Silibinin B Combination in Colorectal Cancer Cells is Mediated by Apoptosis and Autophagy
Authors: Horita Megan Ann , Reed Megan , Ganapathy Aravinda , Ezekiel Uthayashanker 
Published: June 2021

Colorectal cancer (CRC) is the third most commonly diagnosed cancer in men and women in the US. Epidemiological studies have shown that a diet high in fruits, vegetables, and spices is strongly associated with a reduced risk of developing cancer. Dietary cancer protection may be attributable to synergy between low dose phytochemicals present in the diet. We have found that curcumin, the major component of turmeric, and silibinin B, the major component of milk thistle, exert synergistic anticancer activity in CRC. When both compounds are used to treat the CRC cell line, more cells undergo cell death than when the compounds are used independently. We found that the combination of curcumin plus silibinin B mediated cell death by both apoptosis and autophagy.Support or Funding InformationMH, MR, and AG are supported by DeNardo Education and Research Foundation Fellowship.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.