bluuebunny/crossref_metadata_2025_split huggingface dataset:
AKT signaling is essential for functional and structural integrity of the heart
Authors: Goedecke Stefanie , Heinen Andre , Moeller Finja , Deenen Rene , Koehrer Karl , Goedecke Axel 
Published: November 2023

The mammalian heart expresses predominantly two isoforms of protein kinase B (AKT), namely AKT1 and AKT2. Knockout mice for AKT1 and AKT2 respectively, have demonstrated that AKT1 primarily appears to regulate growth whereas AKT2 is rather involved in regulating metabolism. Here we have analyzed common functions of both AKT isoforms in the heart by generating Tamoxifen(OHTX)‐inducible, cardiac myocyte specific AKT1 and AKT2 single and double KO mice (iCMAKT1/2KO).Inactivation of AKT1 and AKT2 resulted in a maximal loss of both isoforms 5 days after start of OHTX‐treatment without a compensatory upregulation of AKT3. The basal level of Ser9 Phosphorylation of GSK3β was significantly reduced in hearts of double KO only, demonstrating that GSK3β is controlled by AKT1 and AKT2 isoforms in CM. Insulin did not stimulate GSK3β phosphorylation. Furthermore, insulin dependent phosphorylation of classical direct and indirect AKT downstream targets like mTor (Ser2448, Ser2841), p70S6 kinase (Thre 389) or S6 ribosomal protein, among others, was shown to be significantly downregulated in iCMAKT1/2KO heart.Functional analysis by echocardiography revealed a progressive decline of pump function characterized by a drop of ejection fraction from initially 62 to 37 % and 31 % on day 10 and day 21, respectively resulting in cardiac failure on day 24. In contrast, the single iCMAKT1 and iCMAKT2 KO mice showed no cardiac depression. Interestingly, wall thickness declined from day 14 to day 21. Concomitantly, cardiac mass declined to 70 %. Gene expression analysis using Agilent 60K microarrays were performed using hearts from single and double knock out mice. On day 10 after KO induction 1095 genes were differentially expressed (P<0.05) and on day 21 this number increased to 7707 (P<0.01, moderated t‐test, Benjamini‐Hochberg correction). On day 10 upon Txf induction Gdf15 (4.9 × up), a typical stress marker for diseased hearts but not ANP was induced in double knock out hearts. On day 21 this expression increased to Gdf15 (58 × up) and also ANP was induced (17.8 × up). None of these expression alterations coud be detected in Akt1 or Akt2 single knock out heart. Ingenuity Pathway analysis identified particularly metabolic pathways as well as EIF2 signalling to be substantially affected.ConclusionExpression of either AKT1 or AKT2 in cardiac myocytes is sufficient to preserve cardiac function whereas loss of both isoforms results in progessive cardiac atrophy and failure.Support or Funding InformationThis work was funded by DFG Grant IRTG1902.
Antioxidant Activity and Protective Effect on PC12 against H2O2 of Epimedium koreanum
Authors: You SoHyeon , Jang Miran , Kim Gun‐Hee 
Published: November 2023

It is well known that Epimedium is bioactive genus of Asian pharmacopoeia. Recent studies have attributed most of these functional properties to its flavonoid glycosides, especially icariin which is the major constituent. In this study, we investigated flavonoids glycosides in Epimedium koreanum and icariin, icaritin, icariside□, icariside□, epimedin A‐C have been identified using HPLC‐DAD. After screening the seven identified flavonoid glycosides by 2,2′‐azino‐bis(3‐ethylbenzothiazoline‐6‐sulfonic acid) (DPPH) assay, icariin and icariside□ presented significant effect on radical scavenging activity. We examined the antioxidant effect of Epimedium koreanum extract, icariin and icariside□ using DPPH, 2,2′‐azino‐bis(3‐ethylbenzothiazoline‐6‐sulfonic acid) (ABTS) and ferric reducing ability power (FRAP) assay. The results showed Epimedium koreanum extract, icariin and icariside□ have effect on antioxidant peroperty in dose dependant manner. Neuroprotective effect against H2O2–induced cell viability in PC12 cells was analyzed using MTT assay. It revealed that Epimedium koreanum extract, icariin and icariside□ showed cell protective effect dose dependantly. From these outcomes, we could identified that icariside□ has potency of functional effect as natural source for human health and further research needs to be carried on.Support or Funding InformationThis work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (No.2016R1A2B4014740)
First‐in‐class Naturally ‐ occurring Bioenergetic Peptide from Hibiscus sabdariffa
Authors: Kam Antony , Loo Shining , Tam James P 
Published: November 2023

Mitochondria produce more than 90% of cellular energy and defects in energy metabolism are a common cause of age‐related diseases1. These diseases include cardiovascular disease, diabetes, neurodegeneration and fatigue2. In a program to identify potential therapeutics against age‐related diseases, we have identified cysteine‐rich peptides, designated as roseltides, from the medicinal plant Hibiscus sabdariffa. Hibiscus sabdariffa of the Malvaceae family, commonly known as roselle, is a shrub cultivated in South‐east Asian countries. The dark red fruit is used to make drinks, syrups and jams. As a folk medicine, it has been used for treating diabetes, cardiovascular and neurodegeneration‐related diseases3. Here, we report the discovery of roseltide rT1, a bioenergetic‐mitochondria‐targeting peptide from Hibiscus sabdariffa that improves bioenergy traits. Roseltide rT1 was isolated and purified through repeated rounds of liquid chromatography. Using a combination of transriptomic and proteomic methods, roseltide rT1 is identified as a 27‐residue peptide with high metabolic stability4. Roseltide rT1 is a cationic and amphipathic peptide which is favorable for cell‐penetration. Using flow cytometry and live‐cell confocal microscopy, we demonstrated that roseltide rT1 is internalized into living cells via endocytosis. Upon cell entry, roseltide rT1 escapes the endosome and localizes to the mitochondria. Functionally, roseltide rT1 increases cellular ATP level. Taken together, this study highlights the discovery of roseltide rT1, as the first naturally‐occurring mitochondria‐targeting peptide with enhancing properties of ATP production. The features of roseltide rT1 display potential as a new mitochondrial‐targeting agent with therapeutic potentials for mitochondrial dysfunctions.Support or Funding InformationThis project was supported in part by the National Research Foundation (NRF‐CRP8‐2011‐05) of the Prime Minister's Office of Singapore.
Cellulose degradation in anaerobic condition by filament fungi
Authors: Mercado‐Garcia Benjamin 
Published: November 2023

Cellulases are powerful enzymes with many potential applications, including agriculture, textiles and biofuels production. Many Fungi are known to be cellulose degraders, secreting powerful cellulases in aerobic environments. But can fungi degrade cellulose in anaerobic conditions? Rose Bengal Agar enriched with sodium nitrate and antibiotics was used to isolate fungi in wood incubated in anaerobic conditions using anaerobic jars together with Gas Pak systems. Isolated fungi were transferred to PDA medium until purified colonies were obtained. Purified colonies were identified using PCR techniques with ITS‐1 F and ITS‐4 R primers. All isolated fungi were grown on PDA and PDA enriched with sodium nitrate in anaerobic conditions to evaluate growth abundance and colony pigmentation. Also, growth was tested for all fungi in liquid media using cellulose strips as the only carbon source. Eight genera were identified using primers ITS‐1 and ITS‐4 including: Aspergillus, Mucor, Phlebia, Fusarium, Botryosphaeria, Neofussicoccum, Schizophyllum and Penicillium. Twenty two of the forty two fungi tested showed good growth in PDA and PDA + nitrate in anaerobic conditions. Secretome was collected from fungi growing in aerobic and anaerobic conditions in liquid media with cellulose strips and proteins were precipitated with acetone:water 4:1 and stored at −20°C, for specific activities assays. SDS PAGE was used to separate cellulases secreted and proteins extracted from SDS PAGE were analyzed by mass spectroscopy. This project will help to identify possible new cellulases produced in anaerobic conditions by fungi traditionally classified as aerobic cellulose degraders.Support or Funding InformationUniversity of Puerto RicoRISE Program
TolC: An important component of bacterial efflux pumps and potential target for ameliorating antibiotic resistance
Authors: Kessler Eric , Whalen Joe , Bradford Hanna , Chavali Vamsi , Engle Davis , Jeng Joshua , Meier Tristin , Merchant Grace , Narayanan Srivats , Song Anna , Sundar Archana , Van Lieshout Emma 
Published: November 2023

Antibiotics are a hallmark of modern medicine, having saved countless lives since the discovery of penicillin in 1928. Bacteria resistant to antibiotics emerged shortly after introduction, and is an increasing problem as bacteria evolve multidrug resistance. Membrane efflux pumps, including AcrAB‐TolC, in gram‐negative bacteria export a variety of substances and provide an intrinsic means for the development of antibiotic resistance. The Blue Valley CAPS 2016–17 SMART (Students Modeling a Research Topic) Team modeled the TolC component of a bacterial efflux pump using JMol and 3D printing technology, and is working to increase antibiotic susceptibility of E. coli using a CRISPR/dCas9 system to inhibit expression of TolC. Efflux pumps, located in the plasma membrane, consist of three proteins; TolC serves as a channel through the periplasmic and outer membrane spaces, while AcrA and AcrB, located in the inner membrane, act as translocases. TolC is a trimeric protein forming a right‐twisted 12‐stranded antiparallel β‐barrel domain, anchoring the protein in the outer membrane, and a left‐twisted 12‐stranded antiparallel α‐helical coiled‐coil domain, extending across the periplasmic space. When translocases AcrA‐B bind a suitable substrate and are energized, TolC is recruited and forms a transient complex. Conformational changes within the coiled‐coils of the α‐helical domain transforms TolC into an open state, allowing entry and movement through its tunnel. Neutralizing the TolC component of efflux pumps using CRISPR/dCas9 may help to prevent bacteria from exporting antibiotics, making them more susceptible to these important drugs.Support or Funding InformationSupported by NIH‐SEPA and ASBMB HOPES grants.
Effects of Tart Cherry Juice on Brachial and Aortic Hemodynamics, Arterial Stiffness, and Blood Biomarkers of Cardiovascular Health in Adults with Metabolic Syndrome
Authors: Johnson Sarah A. , Navaei Negin , Pourafshar Shirin , Jaime Salvador J. , Akhavan Neda S. , Alvarez‐Alvarado Stacey , Litwin Nicole S. , Elam Marcus L. , Payton Mark E. , Arjmandi Bahram H. , Figueroa Arturo 
Published: November 2023

Metabolic syndrome affects greater than one‐third of adults in the United States and is highly associated with the development of cardiovascular diseases. In fact, premature vascular dysfunction in metabolic syndrome may lead to accelerated atherogenesis and arterial stiffening, in large part due to oxidative stress and inflammation in the vasculature. Montmorency tart cherries (Prunus cerasus L.) are rich in bioactive compounds, particularly anthocyanins, known to exert cardiovascular‐protective effects. Previous research suggests that tart cherry juice consumption may improve physiological processes associated with cardiovascular and metabolic health. We conducted a randomized, parallel‐arm, single‐blind, placebo‐controlled pilot clinical trial to investigate the extent to which daily consumption of tart cherry juice would improve parameters associated with cardiovascular and metabolic health including brachial and aortic hemodynamic parameters such as blood pressures and wave reflection, arterial stiffness as assessed by pulse wave analysis and pulse wave velocity, and blood biomarkers of cardiovascular and metabolic health, inflammation, and oxidative stress in men and women between the ages of 20 and 60 years with metabolic syndrome. Nineteen adults with metabolic syndrome consumed 480 mL of tart cherry juice (Tart Cherry; n = 5 males, 4 females) or an isocaloric placebo‐control drink (Control; n = 5 males, 5 females) daily for 12 weeks. Measurements were taken and blood was collected at baseline, 6 and 12 weeks. Oxidized low‐density lipoprotein and soluble vascular cell adhesion molecule‐1 were significantly lower (P = 0.047 and P = 0.036, respectively) in Tart Cherry than Control at 12 weeks. There was a trend for total cholesterol to be lower (P = 0.08) in Tart Cherry than Control at 12 weeks. These results suggest that daily tart cherry consumption may attenuate processes involved in accelerated atherogenesis without improvements on brachial blood pressure, aortic hemodynamics, and arterial stiffness in this population; however, further research is needed to evaluate this.Support or Funding InformationCherry Research Committee of the Cherry Marketing Institute
Soy protein nanoemulsions improve stability and bioavailability of vitamin D
Authors: Alruwaili Nawaf Wanas , Lopez Emely Cristina , Gaur Shashank , Feng H. , Engeseth N.J. , Andrade J.E. 
Published: November 2023

BACKGROUNDDeficiency and insufficiency of vitamin D (VD) afflicts populations worldwide. Fortification of foods with VD has been present for decades; however, its stability in foods is often compromised by its rapid degradation, low absorption and poor water solubility. In this study, soy protein isolate was conditioned using pH shifting and ultrasound treatment to create soy protein‐based nanoemulsions (SPNEs). The objective was to evaluate the stability, bioaccessibility and bioavailability of VD dispersed in SPNEs.METHODSSPNEs were prepared by mixing canola oil (1%, w/w) and soluble SPI (30 mg/mL) containing VD (100 μg/mL; cholecalciferol) and sonicating (20 kHz) 5 min. VD‐containing SPNEs were compared to controls including VD dispersed in water after sonication and in lecithin with canola oil after sonication. VD‐containing SPNEs were freeze dried and evaluated after resuspension. Particle size was measured using dynamic light scattering spectroscopy. VD stability was evaluated after UVB light exposure for 0, 30, 60 and 120 min followed by quantification using and reversed phase HPLC‐UV. Bioaccessibility was evaluated in a two‐compartment in vitro digestion model. Bioavailability was evaluated in adult Long‐Evans hooded rats. Rats were conditioned for a week under a AIN‐93M diet before receiving a gavage dose of: 1) VD‐containing SPNEs (2 mL, 150 μg/mL), 2) Oil with VD (0.5 mL, 300 μg/mL), and 3) Oil without VD (0.6 mL canola oil). After gavage, specific groups of animals (n=3–5) within each treatment were euthanized at 1, 9, 24, and 48 hours after oral dose. Serum 25(OH) VD levels in rats were measured post‐mortem using a colorimetric (450 nm) sandwich ELISA.RESULTSSoy nanoparticles (15–30 nm) were larger (p<0.05) than VD‐containing SPNEs (10–20 nm). VD‐containing SPNEs had higher particle size after freeze drying (50–70 nm; p<0.05). Recovery of VD after 60 min UV exposure was 52.3%, 12.8%, and 9.8% in SPNEs, emulsified in lecithin, or without emulsifier in water, respectively. VD bioaccessibility was higher (p<0.05) in SPNEs (96%) than emulsified in lecithin (69%), or without emulsifier in water (63%). Pharmacokinetic studies in rats showed that oral delivery of VD in SPNEs resulted in 8.1‐fold increase in the AUC (p<0.05) and reaching a Cmax at 24 hours compared to the Oil with VD control.These results revealed that dispersion of VD in SPNEs protects VD from UV exposure and increases its bioaccessibility and oral bioavailability. Future studies will evaluate the sensory properties of SPNEs in food products.Support or Funding InformationUniversity of Illinois at Urbana‐Champaign, King Saud University
Effects of Physical Exercise on Adult Hippocampal Neurogenesis: Changes in DNA Methylation and a Focus on Smad2 Gene
Authors: Trejo Jose Luis , Herrera Antonio , Fontán‐Lozano Ángela , Pons Sebastián , Gradari Simona 
Published: November 2023

Physical activity is an important factor capable of inducing changes in the brain. This study aims to investigate if the expression of certain genes is regulated by changes in the DNA methylation in the hippocampus of the adult mouse, in response to exercise. In particular, the research has focused on the Smad2 gene, manipulating its expression in the dentate gyrus with lentiviral vectors, and studying its role during the process of neurogenesis.First of all, the hippocampus regions from sedentary and runner animals were analyzed using a microarray detecting the DNA methylation status of 24 transcription factors, and then gene expression was assessed by means of a qPCR. Lentiviral vectors were therefore created to over‐express Smad2, or to silence it by means of a shRNA. Afterwards, mice were subjected to bilateral stereotactic injections into the dentate gyrus to inoculate the different kind of lentivirus. Half of the animals from each group remained in their cage for the duration of the experiment, while the other half undertook physical exercise for two weeks. Finally, animals performed behavioural tests to assess activity, state of anxiety and ability in spatial learning and memory. Neurogenesis and modifications in synaptic plasticity were analyzed in the granule neurons with immunohistochemistry techniques.Results show that exercise induces changes in the DNA methylation and it regulates the expression of many transcription factors, such as Smad2. The silencing and over‐expression studies elucidate a role for this gene in the late‐stages of adult hippocampal neurogenesis: Smad2 does not promote cell proliferation and survival but it induces neuron's maturation and differentiation. Moreover, Smad2 silencing compromises the spatial learning abilities in sedentary mice, while exercise is able to reverse the impairments due to the genetic manipulations. This study confirms that exercise alters DNA methylation, it has a role in neural plasticity and, moreover, that Smad2 is involved in the late‐stages of hippocampal neurogenesis.Support or Funding InformationGrant BFU2013‐48907‐R from Ministerio de Economía y Competitividad, Spain
Relationship between Muscularity Concerns and Body Checking Behaviors in Turkish Bodybuilders
Authors: Devrim Asli , Bilgic Pelin , Aslantas Burcu , Hongu Nobuko 
Published: November 2023

ObjectiveMuscle dysmorphia is a common body dysmorphic disorder among male bodybuilders. The major problem is difficulty in diagnosing muscle dysmorphia and often underreported. Muscularity concern is one of the underlying problems in the process of body image disturbance. Researchers have defined muscularity concern as repetitive body checking behaviors more than once in the same day. We aim to investigate the association between muscularity concerns and body checking behaviors among Turkish bodybuilders.MethodsParticipants were 120 male bodybuilders, (mean age 31.05±10.60) recruited from bodybuilding gyms in this study. Their height and weight were measured and Fat Free Mass Index (FFMI) score were calculated. Body checking behaviors (numbers of checking their muscles in a mirror and mirror‐like surfaces) were self‐reported by the bodybuilders. Muscle Dysmorphia Disorder Inventory (MDDI) was used to determine muscularity concerns. The data were analyzed using the IBM SPSS Statistics 23.0. Correlation analyses were used to determine the relationship between the measures of MDDI and the numbers of body checking behaviors.ResultsIn this study it is determined that participants check their muscles in the mirror mean average 9.2 (2–13) times a day, and it was higher in the high‐level MDDI scores compared with the low‐level MDDI scores (relatively 77.6% and 22.4% of the study population) The FFMI scores showed positive correlation with the MDDI scores and body checking behaviors (respectively; r=0,614 and r= 0,390, p=0,001).ConclusionsIt was found that bodybuilders with muscle dysmorphia concerned about their muscularity (higher MDDI score) and more frequent repeated body checking behaviors. Therefore, body checking behaviors and FFMI scores appeared to be a good diagnostic tool for health professionals to use when detecting muscle dysmorphia in bodybuilders.Support or Funding InformationThere is no funding support
6N‐Cyclohexyladenosine Suppresses Shivering in Anesthetized Swine
Authors: Drew Kelly L , Tøien Ø , Kumar Matthew M 
Published: November 2023

Shivering compromises post‐operative recovery and patient comfort. Shivering is also an impediment to targeted temperature management (TTM), now standard of care for cardiac arrest. Without an effective drug to suppress shivering (referred to here as a thermolytic) high cost and difficulty of temperature management is restricting access to TTM outside of large hospitals and for conditions such as stroke. A more efficacious thermolytic is needed for post‐operative control of shivering and to improve patient comfort during TTM. Our prior work in rats, based on strong scientific premise from the study of hibernating animals, suggests that stimulating CNS A1 adenosine receptors (A1AR) by combining the A1AR agonist 6N cyclohexyladenosine (CHA) with the peripherally acting adenosine receptor antagonist 8‐(p‐sulphophenyl)theophylline (8‐SPT) will provide an effective means to control shivering. This approach works in rodents however, thermolytic efficacy has not been demonstrated in a larger mammal that, like humans, depends primarily on shivering thermogenesis to maintain body temperature. To assess the thermolytic efficacy of CHA in 50–55 kg swine, a species that lacks brown adipose tissue, three pigs were anesthetized with Telazol/Xylazine, propofol, or isoflurane and cooled to a target body temperature of 32 to 34°C with a water blanket set to 4°C. Probes measured core body temperature at the tympanum, lower esophagus, rectum and bladder. Electrocardiography, pulse oximetery and arterial blood pressure were monitored. Shivering was measured by respirometry and by a qualitative visual scale. When shivering was noted, CHA was administered (bolus, 4.2mg; infusion,113μg/kg/h). 8‐SPT (bolus, 186mg), atropine (bolus, 0.5mg) or epinephrine (bolus, 100μg) was then given IV to reverse bradycardia and hypotension. At completion, animals were euthanized and tissues collected for histopathology. Results show that CHA inhibits shivering and that 8‐SPT restores blood pressure and heart rate without reversing the thermolytic effect of CHA. No histopathology was noted. In conclusion, CHA is an effective thermolytic in swine.Support or Funding InformationThis work was supported by Be Cool Pharmaceutics LLC and the Mayo Clinic