bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lidocaine blocks the proliferation, Migration, and Epithelial‐Mesenchymal Transition of Human Retinal Epithelial cells
Authors: Kim Yeon A , Kwon Yoon Hyung , Woo Min Seok 
Published: June 2021

IntroductionProliferative vitroretinopathy (PVR) is a major cause of failure in surgery of rhegmatogenous retinal detachment (RRD). The incidence of PVR approximately attains up to 5~10% of RDD and 75% of redetachment after surgery, however, the strategy for precautions or resolving the PVR is very limited. Lidocaine is well known and widely used local anesthetics. We evaluated the effects of lidocaine on epithelial‐mesenchymal transition (EMT) and migration in retinal pigment epithelial cells, which is major cell type involved in the development of PVR, and its mechanism.MethodsAdult retinal pigmented epithelial 19 (ARPE 19) cell line was used and MTT (3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐Diphenyltetrazolium Bromide) assay was performed with various concentrations of lidocaine. We induced ARPE to EMT by TGFβ‐1 and it was demonstrated with western blot of α‐SMA (smooth muscle actin), vimentin, E‐cadherin, and collagen I. The inhibitory effects of lidocaine in TGFβ‐1 signaling were also evaluated with western blot of ERK (extracellular signal regulated kinase), PI3K (Phosphoinositide 3‐kinase), Akt (Protein kinase B), and smad. The change of motile activity by TGFβ‐1 and lidocaine was demonstrated with migration assay.ResultsLidocaine was inhibited the proliferation of ARPE cells in concentration dependent manner after treatment of lidocaine, 24 hours and 48 hours, respectively. Migration activity of ARPE cells were inhibited by lidocaine and the migration of ARPE cells undergoing EMT by TGFβ‐1 was also inhibited significantly. Lidocaine prevented EMT by decreasing the activations of ERK, PI3K, Akt and smad, result in decreasing the expression of α‐SMA, vimentin, and collagen I synthesis and increasing the expression of E‐cadherin.ConclusionsLidocaine blocks the proliferation, migration, and EMT of ARPE cells by inhibition of TGFβ‐1 signaling pathway.Support or Funding InformationThis work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean Government (NRF‐2017R1C1B5017925).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The Effect of Curcumin on P‐glycoprotein Function
Authors: PENG CHI‐WEN , Teng Yu‐Ning , Hung Chin‐Chuan 
Published: June 2021

Multidrug resistance (MDR) is one of the leading cause of cancer treatment failure. P‐glycoprotein (P‐gp) has been reported as a major mechanism of MDR that increased the efflux of drugs. Three generations of P‐gp inhibitors have been developed, however, systemic toxicities limited the clinical application of these compounds. Therefore, identification of the potent and non‐toxic P‐gp inhibitors from natural products may be an alternative choice. The objective of this study was to investigate the inhibitory effect and molecular mechanism of curcumin on human P‐gp efflux function.HEK293 cell were stably transfected with human P‐gp. The MDR1 shift assay was applied to evaluate whether curcumin is a substrate of P‐gp. The effect of curcumin on P‐gp function was evaluated by rhodamine 123 accumulation assay and calcein AM uptake assay. Rhodamine 123 efflux assay was performed to analyze the inhibitory mechanism.Results from cytotoxicity assay and MDR1 shift assay indicated that curcumin is a safe natural product without cytotoxicity and not a P‐gp substrate. The intracellular fluorescence of rhodamine 123 was higher in curcumin treated P‐gp expressed cells than no‐treatment control, suggesting curcumin may inhibit P‐gp efflux function. Results of calcein‐AM uptake assay and rhodamine 123 efflux assay demonstrated that curcumin significantly inhibited P‐gp efflux function in dose dependent manner. Furthermore, curcumin uncompetitively inhibited rhodamine 123 efflux by P‐gp.This study demonstrated that curcumin, sourced from natural plants, as a potential P‐gp function modulator. Although the exploring of novel inhibitors from natural products is still in the early stages, the promising beginning and detailed mechanism investigation provided by this study will be helpful in the future in vivo studies and clinical use.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
AKBA exerts anti‐tumor effects in glioblastoma cells by arresting cell cycle at G2/M phase
Authors: WANG JINHUA , Li Wan , Lyu Yang , Du Guanhua 
Published: June 2021

Glioblastoma (GBM), accounting for about 50 % of all gliomas, is the most common, malignant, and lethal primary brain tumor in adults. Up to now, there is no effective drug for GBM. 3‐O‐Acetyl‐11‐keto‐β‐boswellic acid (AKBA) is one of main active ingredients of the gum resin of Boswellia serrata and Boswellia carterri Birdw. AKBA was reported to inhibit the growth of many cancer cells; however, the precise molecular mechanisms of its anti‐cancer activities in GBM remain unclear. Here, we found that treatment of AKBA in U251 and U87‐MG glioma cells inhibited the cell proliferation, released the cellular LDH, decreased the DNA synthesis, and inhibited the migration, invasion, and colony formation of cells. AKBA also increased the apoptotic rate of cells, decreased the mitochondrial membrane potential, inhibited the activity of caspase 3/7, and decrased the protein expreesion of cleaved‐caspase 3, cleaved PARP in U251 and U87‐MG cells. RNA‐Sequencing analyses showed that AKBA suppressed the expression of pRB, FOXM1, Aurora A, PLK1, CCD25C, p‐CDK1, cyclin‐B1, Aurora B, and TOP2A while increased the expression of p21 and GADD45A, which was further validated by qRT‐PCR and Western blot analyses. These results demonstrated that AKBA induced mitochondrial dependent apoptosis in glioblastoma cells which was associated with arresting the cell cycle at G2/M phase by regulating the p21/ FOXM1/cyclin B1 pathway and inhibiting the mitosis of glioma cells by downregulating the Aurora B/ TOP2A pathway. Taken together, our findings suggest that AKBA might be a promising chemotherapy drug in the treatment of GBM.Support or Funding InformationNational Natural Science Foundation of China (N0. 81573454 for JINHUA WANG, N0. 81703536 for WAN LI and 81703565 for WEIQI FU), CAMS Innovation Fund for Medical Sciences (CIFMS)(2016‐I2M‐3‐007) and Natural Science Foundation of Beijing (7172142).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Isolation, Characterization, and Synthesis of Cuticular Hydrocarbon Natural Products from Drosophila athabasca, A Species of Evolutionary Interest
Authors: Shuler John F , Lin Nar , Gay Brittany L. , Yukilevich Roman , Kehlbeck Joanne D 
Published: June 2021

Drosophila athabasca, a species complex native to North America, provides a unique opportunity to study nascent speciation arising from sexual isolation. Some have suggested that cuticular hydrocarbons (CHCs) influence the sexual selection process. Extensive analyses have resulted in complex understandings of CHC involvement in insect mate preference, with minimal work focusing on D. athabasca. The goal of this study is to identify, synthesize and measure biologically relevant quantities of CHCs present in this species complex. Compilations of synthetic material will allow for biological evaluation and a greater understanding of CHC function in D. athabasca. Gas chromatography ‐ mass spectrometry (GC‐MS) from several isofemale lines of D. athabasca reveal a wide array of functionalities, including: saturated, unsaturated, and branched alkanes, fatty acids, acetates, and esters. Dimethyl disulfide (DMDS) derivatization led to unambiguous determination of positions of unsaturation. CHC identities were confirmed through comparison to synthetic standards. To date, over 100 CHCs have been characterized in D. athabasca using previously described analytical and organic methods. An overview of the analyses and syntheses, along with future directions, will be presented.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Synthesized‐Chlorotoxin‐Conjugated Cytochrome C as a Potential Drug for Targeting Glioma
Authors: Delinois Louis Jean , Ramirez‐Paz Josell , González‐Feliciano Jose A. , Maldonado‐Hernández Rafael , Barcelo‐Bovea Vanessa , Joaquin Ovalle Freisa M. , Fulvio Pasquale F. , Griebenow Kai 
Published: June 2021

Amongst primary brain tumors, gliomas are considered the most lethal malignant tumors due to their resistance to radiation and chemotherapy and the difficulty to accurately localize them within the tissue. Chlorotoxin (Ctx), a small neurotoxin of 36 amino acids isolated from the venom of the Israeli scorpion Leiurus quinquestriatus, binds specifically and with high affinity a 72 kDa chloride channel membrane receptor in human gliomas and was proposed to cross the Blood Brain Barrier. These channels are reported to be absent or in low abundance in healthy tissues or in tumors of non‐glial origin. As a component of the scorpion venom, Ctx induces paralysis in small insects or other invertebrates however, no apparent signs of toxicity have been observed when injected in vertebrates. Cytochrome c (CytC), a small membrane impermeable mitochondrial protein (MW= 12 KDa) that facilitates electron transport in cellular respiration, is also known to mediate apoptosis, a normal process of controlled cell death, through the activation of a caspase cascade. In this work, a chemically synthesized‐Ctx is covalently conjugated to CytC through reversible disulfide bridges to accomplish targeted delivery to a glioma cell line 9L/lacZ from Rattus norvegicus and NIH 3T3 from Mus Musculus. Size exclusion chromatography and mass spectrometry characterization of the Ctx‐CytC conjugate show that the Ctx was successfully attached to CytC. Preliminary results from cell viability essay reveal that the Ctx‐Cytc was 40% more toxic than Ctx alone and more toxic to 9L/lacZ than the normal cell line NIH/3T3. These results suggest that the Ctx‐CytC conjugate can be further developed in order to be considered as an alternative potential targeted drug for treatment of gliomas.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Challenges in the Separation of Purified Cardiac Mitochondrial Membranes
Authors: Rodríguez Graciani Keishla M , Chapa‐Dubocq Xavier R , Javadov Sabzali 
Published: June 2021

BackgroundMitochondria are the bioenergetic engines of the cell, thus maintaining mitochondrial health is essential for meeting energy demands. Mitochondrial function is achieved upon the balance of structural processes that involve mitochondrial biogenesis, fusion and fission. Structural and functional integrity of the mitochondrial membranes, the outer mitochondrial membrane (OMM) and the inner mitochondrial membrane (IMM) is important for the maintenance of the mitochondrial quality control and mitochondrial metabolism. Therefore, elucidation of the individual contribution of each membrane to mitochondrial metabolism and function, as well as mitochondria‐mediated cell survival pathways and cell death is important. In this study, we attempted to set up the methods for isolation of mitoplasts (mitochondria without OMM) and the OMM from the rat heart.MethodsCardiac mitochondria were isolated from Sprague Dawley rats (250–300g) by differential centrifugation and purified via Percoll gradient (continuous layers of 19%, 30% and 60% concentration). Isolation of mitoplasts was performed by incubation in different hypotonic and hypertonic buffers, sonication (20% output/power), and separation of membranes by ultracentrifugation using sucrose continuous gradients (20–80%). Mitochondrial swelling assay was made to confirm the swelling/shrinking method used. Mitoplast formation was validated by monoamine oxidase (MAO) activity, oxygen consumption in the presence and absence of cytochrome‐c and Western Blotting against specific inner and outer mitochondrial membrane proteins.ResultsWestern Blot analysis showed pure isolated mitochondria, validated by the absence of GAPDH (cytosolic marker) upon Percoll gradient. In addition, more than 30% decrease in TOMM20 (OMM specific protein) expression in isolated mitoplasts in comparison to mitochondria. Mitochondrial respiratory rates and MAO activity suggests changes in mitochondrial membrane distribution. Mitochondrial swelling assay showed that cardiac mitochondria were resistant to swelling in hypotonic solution, therefore other methods involving the addition of Ca+2 or EGTA were used to induced separation of mitochondrial membranes.ConclusionDespite application of different preparative approaches, we were not able to isolate purified OMM, and only one method was proved to make a slight reduction of OMM contamination in mitoplasts.Support or Funding InformationSupported by the NIGMS NIH grant SC1GM128210This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Synthetic Biology Approaches To New Chemistry
Authors: Chang Michelle 
Published: June 2021

Living systems have evolved the capacity to carry out many chemical transformations of interest to synthetic chemistry if they could be redesigned for targeted purposes. However, our ability to mix and match enzymes to construct de novo pathways for the cellular production of small molecule targets is limited by insufficient understanding how chemistry works inside a living cell. Our group is interested in using synthetic biology as a platform to study how enzymes function in vivo and to use this understanding to build new synthetic pathways for the production of pharmaceuticals, nanomaterials, and fuels using living cells.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Preventive effect of α‐lipoic acid and ebselen on rat intestine against ischemia/reperfusion injury
Authors: Tunc Turan , Guven Ahmet , Topal Turgut , Kul Mustafa , Korkmaz Ahmet , Gundogdu Gokhan , Onguru Onder , Ozturk Haluk 
Published: June 2021

Purpose: Reactive oxygen species (ROS) and reactive nitrogen species(RNS) generated during reperfusion of the tissue are characteristic of ischemia and reperfusion (I/R) injury. The present study was designed to evaluate whether a‐Lipoic Acid (a‐LA) and Ebselen have protective effect in intestinal I/R injury.Methods: Fourty Sprague‐Dawley rats were divided into five groups equally: Group‐1 Sham‐operated; Group‐2 I/R; Group‐3 I/R+a‐LA; Group‐4 I/R+Ebselen; Group‐5 I/R+a‐LA+Ebselen. Intestinal ischemia for 45 min and reperfusion for 3 days were carried out. Ileal specimens were obtained to determine the tissue levels of Malondialdehide (MDA), Protein Carbonyl (PC) content, Superoxide dismutase (SOD) and Glutation Peroxidase (GPx) and histologic changes.Results: There was a statistically significant decrease in SOD and GPx levels, with an increase in MDA and PC content and intestinal mucosal injury in intestinal I/R group (p<0.05). a‐LA and Ebselen led to a significantly increase in SOD and GPx level, with a decrease in MDA and PC content and intestinal injury when compared with I/R group, (p<0.05). Although shortness of villous and epithelial lifting was seen in the rats subject to I/R, there was slightly injury in mucosa in treatment groups.Conclusion: a‐LA and Ebselen played significant protective role in attenuating I/R injury of the intestine by scavenging ROS and RNS.
Effects of dietary fish oil (FO) supplementation on the skeletal muscle blood flow (BF) response to submaximal treadmill exercise
Authors: Hammel Lauren Elizabeth , Marshall Ben J , Hageman Karen S , Poole David C , Stebbins Charles L , Musch Timothy I 
Published: June 2021

Dietary supplementation (SUPP) with FO containing docosahexaenoic (DHA) and eicosapentaenoic acid (EPA) has been demonstrated to produce advantageous effects on vascular function. Specifically, FO SUPP has resulted in enhanced brachial artery dilation during rhythmic handgrip exercise (EX). The effects of FO on BF during dynamic full body EX, however, remain unknown.PURPOSE:To test our hypothesis that 6 weeks of dietary SUPP with DHA and EPA enhances the regional BF response to submaximal treadmill EX in the rat hindlimb.METHODS:Following 6 weeks of dietary SUPP with safflower oil (SO) (control; n = 9) or FO (n = 8), heart rate (HR), mean arterial pressure (MAP), and BF to the hindlimb were measured at rest and during submaximal treadmill EX (20 m/min, 10%) via radiolabeled microspheres in male Sprague‐Dawley rats.RESULTS:HR and MAP were not different between SO and FO at rest or EX (P<0.05). BF was not different between SO and FO at rest. During EX, FO exhibited greater BF in 8 of the 28 muscle parts measured as well greater BF (158±9) to the total hindlimb musculature than SO (128±10ml/min/100g) (P<0.05).CONCLUSION:These results demonstrate that 6 weeks of dietary SUPP with FO results in enhanced BF to the hindlimb during submaximal EX. Thus, SUPP with FO may have therapeutic effects on oxygen delivery and vascular function in patients with impaired vascular function and EX tolerance.
Micronutrient Deficiencies in a Long Term Acute Care Hospital
Authors: Parkin Courtney , Rollins Carol 
Published: June 2021

Background: The roles of micronutrients and the consequences of their deficiencies in human metabolism, immune function and wound healing are well documented. However, the prevalence of micronutrient deficiencies within the hospital setting is unknown.Objectives: To identify the prevalences of zinc, selenium, vitamin A, vitamin D, and vitamin B12 deficiencies in a long term acute care hospital setting.Results: The number and percent of serum levels indicative of micronutrient deficiency are shown in Table 1.Conclusions: Micronutrient deficiencies within the long term acute care environment appear to be widespread. Patients with a history of poor dietary habits and chronic illness are at high risk of nutrient deficiencies, including micronutrient deficiencies.
Predictors of 5 y change in cardio‐metabolic risk among Guatemalan adults
Authors: Gregory Cria O. , Ramirez‐Zea Manuel , Martorell Reynaldo , Stein Aryeh D. 
Published: June 2021

We examined 376 Guatemalan adults in 1997â8 (age 24Â±3 y) and in 2002â4. Overweight (BMIâ¥25 kg/m2) and obesity (BMIâ¥30 kg/m2) prevalence increased (23% to 46% and 6% to 15%, respectively, both p<0.01), as did percent body fat (%BF; 23.3Â±9.8 to 27.0Â±10.2 %), triglycerides (129.2Â±64.5 to 161.0Â±80.2 mg/dL), the ratio of total to HDL cholesterol (TC:HDL‐c; 4.3Â±1.0 to 4.5Â±1.5 mg/dL), glucose (85.7Â±9.3 to 92.1Â±18.3 mg/dL), and diastolic blood pressure (DBP; 68.8Â±8.7 to 70.0Â±8.5 mmHg) (all P<0.05). 5y increase in %BF was associated with lower physical activity level at baseline and was higher among men; women had greater 5y increase in DBP. Age, rural/urban residence, schooling, socio‐economic status, smoking, and dietary energy and fat intakes were not associated with 5y changes in any risk factor examined. In adjusted models, 5y change in %BF was associated with changes in triglycerides (Î²= 4.6; 95% CI=2.3, 6.8 mg/dL per %), TC:HDL‐c (Î²= 0.09; 95% CI=0.05, 0.1 per %), and DBP (0.7; 95% CI=0.5, 1.0 mmHg per %). The 5y increases in cardio‐metabolic risk factors were primarily predicted by changes in %BF. Promotion of increased physical activity may help prevent adverse changes in body composition and consequent cardio‐metabolic risk.Funding: NIH TW005598; AHA Pre‐doctoral fellowship (COG)
Genetic Polymorphism Of Glutathione S‐Transferase (GST) And Susceptibility To And Severity Of Chronic Obstructive Pulmonary Disease (COPD)
Authors: Hemimi Neveen Salah El Din , Attar May Mahmoud Al , Elwahab Mahmoud M Adb 
Published: June 2021

Background: Chronic tobacoo smoking is a major risk factor in the development of COPD. However, it is estimated that only 10–20% of chronic heavy smokers will develop symptomatic COPD. This indicates the possible contribution of environmental or genetic cofactors to the development of COPD in smokers.Aim: To study the relationship between GST polymorphism and susceptibility to and severity of COPD in smokers. Method: A case control study was done on 140 patients with COPD and 140 matched controls. All subjects were smokers or exsmokers. The GSTM1 and GSTT1 genotypes were identified by polymerase chain reaction in peripheral blood DNA samples. Analysis of data was done by IBM computer using SPSS program.Results: The proportion of GSTM1‐null genotypes was significantly higher in patients with COPD than in control subjects (62.2% versus 32.2%). The odds ratio was 3.5 (95% confidence interval (CI) =2.1–5.7). Moreover the patients with GSTM1 null genotype were at high risk of developing the severe type of COPD. The odds ratio was 3.14 and (95% CI= 1.5–6.7). However the genotype frequencies of GSTT1‐null genotype did not show significant difference between groups.Conclusion: Our data provide evidence that smokers with null genotype of GSTM1 were more susceptible to develop the severe type of COPD. Keyword: Genetic polymorphism, COPD, GSTT1, GSTM1. Source of Research support: Dubai Medical College for Girls.
Forms of Vitamin E have Opposing Effects on Experimental Asthma
Authors: Cook‐Mills Joan Marie , Berdnikovs Sergejs , Abdala‐Valencia Hiam , McCary Christine , Somand Michelle , Bryce Paul 
Published: June 2021

We previously reported that the endothelial cell adhesion molecule VCAM‐1 signals through reactive oxygen species generated by NOX2 and that this regulates leukocyte trafficking in vitro and in vivo. Therefore, we determined whether leukocyte migration is modulated by two major dietary forms of the antioxidant vitamin E, (d)‐α‐tocopherol (aT) and (d)‐γ‐tocopherol (gT). Mice were treated daily with physiological levels of aT or gT after sensitization and before challenge with the antigen ovalbumin, a model of experimental asthma. aT significantly inhibited inflammation in the lung and inhibited airway hyperresponsiveness (AHR). Surprisingly, gT exacerbated inflammation and AHR in the lung. Most interestingly, when gT and aT were co‐administered, gT ablated the benefit of aT. In addition, gT antagonized aT inhibition of leukocyte transendothelial migration in vitro. In summary, aT and gT have opposing effects on inflammation. These data have implications on the design and interpretation of clinical studies with mixed tocopherols in supplements and diets. Reported studies indicate that aT is beneficial for experimental asthma in mice and for asthma in Europeans who consume diets low gT but not for Americans who consume diets high in gT, suggesting that differences in the outcomes in these reports on vitamin E may, in part, reflect the opposing effects of α‐tocopoherol and γ‐tocopherol.(NIH R01 HL069428 to JC‐M)