bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of Na‐H Exchanger‐2 in Experimental Colitis: Mechanism of Regulation of Expression
Authors: Khan Islam , Soleiman Amal Ali , Thameem Farook
Published: November 2023

Background

The Na‐H exchanger (NHE) perform an electroneutral uptake of NaCl and water from the lumen of the gastrointestinal tract. There are multiple distinct NHE isoforms, some of which show an altered expression in the inflammatory bowel diseases (IBD). In this study, we examined a role of NHE‐2 in experimental colitis.

Methods

Colitis was induced in male Sprague‐Dawley rats by intra‐rectal administration of trinitrobenezenesulfonic acid (TNBS). On day 6 post‐TNBS, the animals were sacrificed, colon and ileal segments were taken out, cleaned with phosphate buffered saline and used in this study.

Results

There was a significant decrease in the level of NHE‐2 protein as measured by ECL western blot and confocal immunofluorescence micrometry. The levels of NHE‐2 mRNA and heteronuclear RNA measured by an end‐point RT‐PCR and the real time PCR were also decreased significantly in the inflamed colon. However there was no change in the level of NHE‐2 protein in response to in‐vitro TNF‐α treatment of an uninflamed rat colon. These changes were selective and localized to colon as actin, an internal control remained unchanged. The confocal fluorescence microscopy revealed co‐localization of NHE‐2 and NHE‐3 in the brush borders of the colonic epithelial cells. Inflamed colon showed a significant increase in the myeloperoxidase activity and colon hypertrophy, and a significant decrease in the body weight and goblet cells' mucin staining. These changes were not conspicuous in the non‐inflamed ileum.

Conclusions

These findings demonstrate suppression of NHE‐2 expression on the brush borders in the colonic epithelial cells which is regulated transcriptionally. However a role of TNF‐α in the regulation of NHE‐2 is discounted in the present model of colitis. This decrease in the NHE‐2 expression will lead to a loss of electrolyte and water uptake thus contributing to the symptoms associated with IBD.

Support or Funding Information

The Kuwait University, Research Grant No. [YM 12/15]. Prof Khan, Anatomy for his help in tissue block preparation for histochemistry and confocal microscopy. Research Core Facility, Health Sciences, the Kuwait University for using their facility to conduct confocal immunofluorescence experiments.
Control of PI4P turnover by endogenous OSBP for fast cholesterol transport at membrane contact sites
Authors: Mesmin Bruno , Bigay Joëlle , Polidori Joël , Lacas‐Gervais Sandra , Antonny Bruno
Published: November 2023

We have demonstrated previously that Oxysterol‐Binding Protein (OSBP) counterexchanges phosphatidylinositol 4‐phosphate (PI4P) for cholesterol at membrane contact sites between the endoplasmic reticulum (ER) and the Golgi. Because PI4P is produced in the Golgi but consumed by a specific phosphatase when it reaches the ER, we have proposed that OSBP uses PI4P as a fuel to direct cholesterol export from the ER, against its cellular concentration gradient. By using a potent OSBP inhibitor, we now provide evidence that the sole activity of endogenous OSBP strongly influences PI4P turnover and intracellular distribution of cholesterol. We show that OSBP constantly consumes more than half of the total Golgi PI4P. We also found that blocking the PI4‐kinase PI4KIIIβ, which typically operates in the vicinity of OSBP, triggers PI4P oscillations across the Golgi. These oscillations result from the production of PI4P by the distant PI4‐kinase PI4KIIα, and PI4P consumption by OSBP. Collectively, these data illustrate the spatiotemporal coupling between PI4P turnover and OSBP‐mediated cholesterol transport in a cellular context.

Support or Funding Information

This work is supported by the Agence nationale de la recherche (ANR‐15‐CE11‐0027‐02).
Interaction between a 70‐kDA heat shock protein and phosphatidylserine in stressed human cells
Authors: Bilog Andrei D , Labanieh Cedra , Nikolaidis Nikolas
Published: November 2023

Seventy‐kilodalton heat shock proteins (Hsp70s) are molecular chaperones playing essential roles in protein homeostasis and cellular survival. Apart from their indispensable roles in cellular homeostasis specific Hsp70s also localize at the plasma membrane and bind to several lipids, including phosphatidylserine (PS). The interaction of Hsp70s with PS regulates important processes, like microautophagy and cell death. However, the conditions that trigger and promote the interaction between Hsp70s and intracellularly localized PS in human cells remain unknown. To shed light to this newly described property of Hsp70s, we tested whether heat‐shock, a stress known to affect both protein expression and membrane lipid composition, triggers the binding of HspA1A, a stress inducible Hsp70, to PS. To this end, we first determined whether HspA1A and the C2 domain of lactadherin (Lact‐C2), a known PS‐biosensor, compete for binding to intracellular PS. Specifically, HeLa cells were subjected to mild heat‐shock and the competition was assessed by quantifying the amount of membrane localized HspA1A in the presence or absence of the Lact‐C2 protein. These imaging experiments revealed that in the absence of Lact‐C2 HspA1A's membrane localization increases continuously after heat‐shock and reaches a maximal value at 8 hours during recovery. In the presence of Lact‐C2, however, HspA1A's membrane localization was minimal and did not show an increase during recovery after heat‐shock. These experiments were verified using cell surface biotinylation. In these experiments, Hek293 cells, after heat‐shock were incubated with membrane impermeable biotin, lysed, and incubated with streptavidin agarose beads, and the biotinylated proteins were analyzed by western blots and quantified using densitometry. Collectively, these results strongly suggest that HspA1A binds to intracellular PS, and that HspA1A's membrane localization and anchorage depends on its interaction with PS. These observations institute PS as a new and dynamic partner in the cellular stress response and establish the required foundation to directly assess the biological implications of this newly described and largely uncharacterized function of Hsp70s.

Support or Funding Information

This project was supported by funds from NIH and CSUF to NN
Understanding Ethanol Hexanoyl Transferase (Eht1) Localization to Lipid Droplets and the Endoplasmic Reticulum in Saccharomyces cerevisiae
Authors: Zhu Jie , Wheeldon Ian
Published: November 2023

Lipid droplets (LDs) are ubiquitous organelles that play central roles in energy and lipid metabolism. They have a unique structure: a core of neutral lipids, composed of tryacylglyceride (TAG) and sterol esters (SEs), surrounded by a phospholipid monolayer. LDs are also decorated with proteins that mediate important metabolic functions and inter‐organelle communications. However, the mechanisms protein targeting to LDs are not well understood and still under investigation. It is understood that proteins with a membrane‐embedded, hydrophobic hairpin motif can access LDs from the endoplasmic reticulum (ER) either during LD formation or through ER‐LD membrane bridges. Another proposed mechanism is that proteins are able to access and bind to LD surface from cytosol through amphipathic helices, hydrophobic domains, lipid modifications, and protein‐protein interactions. Our protein of interest is Eht1 an acyl‐coenzyme A: ethanol O‐acyltransferase from Saccharomyces cerevisiae. Our data shows that Eht1 localizes to the ER and subsequently to LDs; however, it lacks hydrophobic hairpin motifs, has no clear transmembrane domains, and there is no evidence of amphipathic terminal helices or other known LD targeting domains. The aim of this work is to understand the trafficking mechanisms of Eht1 from ER to LDs in S. cerevisiae. Structure and function analysis suggests that both N‐ and C‐termini are crucial for its membrane association. In addition, fluorescence microscopy analysis suggests that the ER translocon may be related to the translocation process of Eht1. Furthermore, to understand how Eht1 interactions with other proteins contribute to the trafficking, we conducted a series of immunoprecipitation experiments and identified associated proteins by mass spectrometry (MS). We are currently exploring the genetic interactions between the MS‐identified proteins and Eht1 through the generation of knockout library using CRISPR/Cas9 genome editing.

Support or Funding Information

This work was supported the National Science Foundation and the University of California, Riverside.
Identification of NPC1 as the target of U18666A, an inhibitor of lysosomal cholesterol export and Ebola infection
Authors: Lu Feiran , Brown Michael , Goldstein Joseph
Published: November 2023

Niemann‐Pick C1 (NPC1) is a lysosomal membrane protein that exports cholesterol derived from receptor‐mediated uptake of LDL, and it also mediates cellular entry of Ebola virus. Cholesterol export is inhibited by nanomolar concentrations of U18666A, a cationic sterol. To identify the target of U18666A, we synthesized U‐X, a U18666A derivative with a benzophenone that permits ultraviolet‐induced crosslinking. When added to CHO cells, U‐X crosslinked to NPC1. Crosslinking was blocked by U18666A derivatives that block cholesterol export, but not derivatives lacking blocking activity. Crosslinking was prevented by point mutation in the sterol‐sensing domain (SSD) of NPC1, but not by point mutation in the N‐terminal domain (NTD). These data suggest that the SSD contains a U18666A‐inhibitable site required for cholesterol export distinct from the cholesterol‐binding site in the NTD. Inasmuch as inhibition of Ebola requires 100‐fold higher concentrations of U18666A, the high affinity U16888A‐binding site is likely not required for virus entry.
Organelle‐specific Regulation of V‐ATPase Activity by Inositol Phospholipids
Authors: Kane Patricia M. , Banerjee Subhrajit
Published: November 2023

All eukaryotic cells have multiple acidic compartments, including lysosomes, endosomes, the Golgi apparatus, and regulated secretory granules, that are tuned to distinct pH ranges essential for their functions. It is not fully understood how precise organelle pH ranges are established and maintained in vivo. We have found that organelle‐specific isoforms of the yeast V‐ATPase, the proton pump primarily responsible for organelle acidification, specifically interact with phosphoinositides (PIs) characteristic of the organelles where they reside. V‐ATPases in the yeast lysosome‐like vacuole contain the Vph1 isoform of the Vo a‐subunit, the largest integral membrane subunit of the enzyme. The Vph1 isoform interacts specifically with the late endosome/vacuole‐specific lipid PI(3,5)P2, and V‐ATPase activity in the vacuole increases under conditions that trigger an increase in PI(3,5)P2, such as salt shock (Li et al (2014) Mol. Biol. Cell 25:1251). Recently we have found that the Golgi isoform of this subunit, Stv1, interacts specifically with PI(4)P, a PI lipid enriched in Golgi membranes. Both Stv1 and Vph1 contain N‐terminal cytosolic domains attached to an 8‐helix, C‐terminal transmembrane domain critical for proton transport. In yeast cells, an engineered cytosolic domain of Stv1 (Stv1NT) is recruited from the cytosol to the membrane in a PI(4)P‐dependent manner. In vitro, bacterially expressed Stv1NT binds specifically to PI(4)P‐containing liposomes in a flotation assay. Neither Vph1 nor Stv1 contain canonical PI binding sites, but we have identified a single point mutation in Stv1NT that compromises Stv1NT binding to PI(4)P‐containing liposomes. Introduction of this mutation into full‐length Stv1 in yeast cells has little effect on Stv1 localization, but reduces V‐ATPase function. This suggests that PI(4)P is required for activity of Stv1‐containing V‐ATPases at the Golgi apparatus. Consistent with this, a pik1ts mutation, which compromises PI(4)P synthesis at the Golgi, also compromises function of Stv1‐containing V‐ATPases. Taken together, these data suggest that isoforms of the V‐ATPase Vo a‐subunits interact with specific PI head groups, and that these interactions provide organelle‐specific input into V‐ATPase function. Mammalian cells express four isoforms of the Vo a‐subunit, corresponding to yeast Vph1/Stv1. In vitro experiments with expressed cytosolic domains of the human Vo a‐subunit isoforms reveal that some of these isoforms also interact with specific PI lipids. Specifically, the Vo a2 isoform, shown previously to function at the Golgi, binds specifically to PI(4)P. These data indicate that the extent of organelle acidification may be determined in part by resident Vo a‐subunit isoforms and their interactions with specific phosphoinositides, which provide both organelle identity and regulatory signals.

Support or Funding Information

Supported by NIH GM50322
Studying the Effect of negative curvature on amphipathic α‐helix model protein binding to an oil/buffer interface
Authors: Mirheydari Mona , Mann Elizabeth K. , Kooijman Edgar E.
Published: November 2023

Lipid droplets, a focus of resurgent interest, are dynamic cell organelles that play roles in storing energy, synthesizing steroid hormones, and building new membrane. In this work, we used a model system consist of a triolein drop formed in a physiologically‐relevant buffer and covered with phospholipid monolayer to study the biophysics of lipid droplets. Experiments are done using our home‐build droplet tensiometer in a temperature controlled room. We use interfacial tension to characterize the surface of the droplet before and after addition of the protein to the buffer. ApoLp‐III is a model protein for the amphipathic α‐helix bundle domain in proteins associated with lipid droplets, e.g. the perilipins. Previous work used POPC to form the phospholipid monolayer surrounding the oil droplet. Here, we used POPC, and mixtures of POPC, and the following lipids: POPE, POG, and POPA to study the effect of effective molecular shape (i.e. spontaneous curvature), head group charge and size in protein interacting to the oil/buffer interface. Our data shows that the affinity of the protein binding to the interface increases for monolayers made up of POPC lipid mixed with negatively charged lipids. We compared the results for native and folded apoLp‐III (which contains a disulfide bond) to explore the role of unfolding on the protein affinity with a POPC monolayer.
Stressing Interdisciplinarity to Mold the Undergraduate Experience
Authors: Keller Chelsea M , Bridges Britney E , Roney James N , Dries Daniel R
Published: November 2023

In the tradition of the liberal arts, Juniata College promotes an environment conducive to interdisciplinary exploration. Many students, however, spend their early academic years taking discipline‐specific courses, leaving non‐disciplinary electives for their junior and senior years. In order to introduce freshmen to interdisciplinary thinking, two undergraduate students and two faculty mentors worked together to co‐develop a pilot course titled “From Lab to World”. As a freshman‐level seminar, this course has the unique opportunity to shape how freshmen will approach the rest of their college career. “From Lab to World” stresses to freshmen the necessity of interdisciplinarity both when working in scientific research teams and when addressing the local and global problems we face as citizens. The class is composed of two modules: personalized genomics and infectious diseases. Within each module, students worked through two problem‐based learning projects and two essays. For stimulation of interdisciplinary thought, the course utilized external speakers, Juniata professors from departments across campus, and various supplementary sources, including film and popular literature. The combination of these media empowered the students to take a hand in their own learning and develop the skills necessary to think critically and constructively regarding social issues. Creating and presenting this course has allowed for our own development both professionally and academically. This experience has ultimately fostered an environment that not only harbors interdisciplinary collaboration but also allows students to realize the necessity of addressing social justice and public health.

Support or Funding Information

This project was supported by a grant to Juniata College from the Howard Hughes Medical Institute through the Precollege and Undergraduate Science Education Program.
The Disruption of Nuclear Export and Protein Localization with 5‐Fluorouracil
Authors: Nickle Audrey , Bischak Melissa , Higby Kelly , Resendes Karen K
Published: November 2023

The alteration of nuclear transport is an essential component of apoptosis, thus making the disruption of this process as well as the nuclear pore complex (NPC) an important aspect of researching cancer treatments aimed at triggering cell death. The chemotherapies 5‐fluorouracil (5‐FU) and the camptothecin derivatives irinotecan and topotecan, are linked to altered nuclear transport of specific proteins; however, their general effects on the NPC and nuclear transport during apoptosis have not been characterized. We demonstrate here that 5‐FU, but not topotecan increases NPC permeability, and disrupts Ran‐mediated nuclear transport before the disruption of the NPC. Combination treatments of 5‐FU with topotecan or irinotecan similarly disrupted nuclear transport before disassembly of the NPC. In both single and combination treatments nuclear transport was disrupted before caspase 9 activation, indicating that 5‐FU induces an early caspase‐independent increase in NPC permeability and alteration of nuclear transport. The process of nuclear transport involves the use of several karyopherin family proteins, including the export protein Crm1. Because Crm1‐mediated nuclear export of target proteins is linked to drug resistance we also examined the effect of 5‐FU on the nuclear export of topoisomerase, the protein target of irinotecan and topotecan, which is known to be excessively exported by Crm1 in some cancer types. 5‐FU treatment led to accumulation of topoisomerase in the nucleus and recovered the loss nuclear topoisomerase induced by irinotecan or topotecan, a known cause of drug resistance. Additional cargoes of Crm1 include several tumor suppressors whose exclusion from the nucleus dysregulates cell cycle progression or prevents apoptosis. One such example is p53, which must be nuclear to upregulate its target genes. We show that 5‐FU and combinations of 5‐FU and topotecan or irinotecan lead to nuclear accumulation of p53. Our results reveal details of the mechanism of apoptosis induction for 5‐FU and camptothecin therapies in terms of nuclear export and allows us to look towards the involvement of 5‐FU induced inhibited nuclear export and thus nuclear retention of tumor suppressors in other combination therapies. Future aims of this research will be directed towards looking at additional factors associated with Crm1, like p27 and p21 as well as combining 5‐FU with additional drugs such as Gemcitabine or Ibrutinib, which are known to be more effective in combination with Crm1 inhibition.
Identification of Regulators of Lysosome Formation
Authors: Le Gloria T , Jackson Nathan , Shaikh Nabeel , Shearon Angela , Fares Hanna
Published: November 2023

Lysosomes are membrane‐bound organelles that serve as the major degradative compartments for endocytic, phagocytic, and autophagic materials targeted for destruction in eukaryotic cells. This degradation is critical to many physiological processes, including processing endocytosed nutrients, down‐regulating signaling receptors, presenting antigens, killing pathogenic organisms, and degrading normal and abnormal cellular proteins. In addition, lysosomes mediate some cell death pathways and repair damage to the plasma membrane. Lysosomes are formed in complex eukaryotes by the budding of a small nascent lysosome from a late endosome/hybrid organelle, movement of the nascent lysosome away from the hybrid organelle while maintaining a membrane bridge, and scission of the membrane bridge to release a discrete primary lysosome. We had previously identified the Mucolipidosis type IV protein TRPML1 as a regulator of the scission step during lysosome formation. Here, we describe the identification of additional regulators of this process, including actin that provides the force for moving nascent lysosomes away from late endosomes/hybrid organelles.
Overexpression of manganese superoxide dismutase in mouse liver leads to defects in oxidative phosphorylation
Authors: Steyl Samantha
Published: November 2023

Non‐alcoholic fatty liver disease (NAFLD) is a chronic disease that is characterized by inflammation in the liver. This inflammation is due primarily to an increase in reactive oxygen species, and therefore antioxidant therapy can reduce the severity of the disease. However, these antioxidants have also been met with negative side effects, which warrants further investigation. Manganese superoxide dismutase, or MnSOD, is a mitochondrial antioxidant enzyme that converts then reduces superoxide levels by converting them into hydrogen peroxide. Hydrogen peroxide is then detoxified by a number of mitochondrial antioxidant enzymes. Although genetic overexpression of SOD2 could be beneficial to the treatment of NAFLD, preliminary data has shown that mice with SOD2 overexpression actually demonstrate defects in oxidative phosphorylation. These defects include reductions in levels of complex II and V measured by blue native PAGE, and reductions in levels of complex II, III and IV measured by SDS‐PAGE. Western blot results for reduction in levels of complex I, II, and III are under investigation. These data indicate that antioxidant therapy may have unexpected complications that should be considered before administration of these drugs.
Bioaccessibility and intestinal cell uptake of astaxanthin from salmon and commercial supplements
Authors: Chitchumroonchokchai Chureeporn , Failla Mark L.
Published: November 2023

We compared the bioaccessibility of astaxanthin (Ast) in uncooked and cooked wild and aquacultured salmon, Ast‐supplements and krill oil. Salmon flesh contained free E‐ and Z‐Ast, whereas Ast esters were predominant in commercial supplements and krill oil. Wild salmon contained ~10 times more Ast than aquacultured salmon; canthaxanthin was abundant (79.5 ± 4.6% of total keto‐carotenoids) in the latter. Cooking wild and acquacultured salmon using common home styles decreased Ast content by 48–57% and 35–47%, respectively. The efficiency of transfer of Ast into mixed micelles during simulated digestion of uncooked wild salmon was 43%, but only 12% for uncooked acquacultured salmon. Cooking wild salmon decreased the bioaccessibility of Ast, although it remained significantly greater than that for uncooked and cooked acquacultured salmon. The bioaccessibility of Ast (41–67%) after digestion of soft‐gel supplements containing Ast was ≥ that in uncooked wild salmon; bioaccessibility of endogenous Ast in phospholipid‐rich krill oil supplement was 68%. Greater than 95% of bio accessible Ast in digested supplements was unesterified. Apical uptake of E‐Ast in micelles generated during digestion of uncooked and cooked wild salmon was similar. Apical uptake and basolateral secretion of E‐Ast by Caco‐2 cells was greater after exposure to micelles generated during digestion of Ast‐enriched krill oil than digested uncooked wild salmon, suggesting that digestion products of phospholipid‐rich krill oil enhance Ast bioaccessibility and bioavailability. Because wild salmon contains health promoting components such as omega‐3 fatty acids and bioactive peptides in addition to Ast, it should be considered as a dietary source of bioavailable Ast.

Support or Funding Information

The Ohio State Agriculture Research and Development Center
Uptake and Metabolism of Dietary β‐Apocarotenoids by Caco‐2 Intestinal Cells
Authors: Durojaye Boluwatiwi O , Riedl Kenneth M , Curley Robert W , Harrison Earl
Published: November 2023

Absorption and metabolism of dietary provitamin A is important, especially in populations whose vitamin A intake is obtained solely from carotenoids in plant based diets. We have detected low but significant quantities of β‐apocarotenoids in high β‐carotene foods. Nothing is known about the extent or mechanisms of intestinal absorption of β‐apocarotenoids, products of β‐carotene cleavage with potent biological activities. This research aimed to determine the kinetics of absorption, transport and metabolism of β‐apo‐8′‐carotenal, β‐apo‐10′‐carotenal and β‐apo‐13‐carotenone using Caco‐2 intestinal cells as a model. There was rapid uptake of β‐apo‐8′‐carotenal into the cells. After uptake, β‐apo‐8′‐carotenal was rapidly converted to a major metabolite identified by HPLC‐UV and LC/MS as β‐apo‐8′‐carotenoic acid. Similarly, β‐apo‐10′‐carotenal was rapidly taken up by the cells and converted to two major metabolites. Their identities are still under investigation. Finally, the cellular uptake of β‐apo‐13‐carotenone was rapid and this compound was quickly degraded to products undetectable by HPLC‐UV analysis. Understanding mechanisms of absorption and metabolism of these compounds relative to their quantities in foods is critical in exploring their functions and may help further understanding of the metabolic effects of β‐carotene.

Support or Funding Information

NIH Grant R01‐HL049879 and funds from the Virginia M. Vivian Graduate Student Research Award
An open label study to evaluate the effect of Kaempferia parviflora in support of erectile function and male sexual health among overall healthy males 50–70
Authors: Hirsh Steven , Huber Luke , Stein Richard , Schmid Kira , Swick Andrew , Joyal Steven
Published: November 2023

Background

Kaempferia parviflora (KP) is an herbaceous plant from the family of Zingiberaceae. The KP rhizomes contain numerous flavonoids, two of which, 5,7‐dimethoxyflavone (DMF) and 5,7,4‐trrimethoxyflavone (TMF), are major constituents. Studies on isolated rat aortic rings revealed DMF causes endothelium‐dependent relaxation and vasodilation, effects partly mediated by the NO‐cGMP and cyclooxygenase pathways. In vitro studies noted an increased mRNA and protein expression of endothelial nitric oxide synthase (eNOS), which is present in the endothelium of the penile vasculature and sinusoidal endothelium within the corpora carvernosa, and concluded this may result in an improvement in endothelial function. Experiments on rats suggested this plant extract may enhance copulatory behavior partly via the induction of hypothalamic dopaminergic D1 receptor expression. Additionally, a study on healthy elderly male volunteers revealed KP may increase blood flow to enhance penile circumference, length, and rigidity.

Objectives

The primary objective of this study was to investigate the effectiveness of KP on erectile function among overall healthy males aged 50–70 utilizing the International Index of Erectile Function (IIEF) questionnaire. Secondary objectives included assessment of mean changes in blood levels of free testosterone, total testosterone, estradiol, DHEA‐S, PSA, total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides, as well as mean response to the Global Assessment Question. Also assessed were changes in health‐related quality of life scores and mean changes in body weight.

Methods

Each subject received a formulation containing KP for 30 consecutive days. Assessments, questionnaires, and laboratory testing were completed on Day 30. Baseline and Day 30 values were compared for all subjects who completed the clinical trial.

Results

A total of 13 subjects completed the trial. The Day 30 analysis showed a statistically significant mean increase in scores attained on the IIEF questionnaire related to total score, erectile function domain, intercourse satisfaction domain, and orgasmic function domain. For the Global Assessment Question, 61.5% of subjects noted the product improved their erections. There were no statistically significant changes observed for the other parameters measured.

Conclusion

The treatment demonstrated improvement in certain study parameters related to erectile function and male sexual health. Results point towards the need for additional controlled studies with larger sample sizes. The study treatment was generally well tolerated.

Support or Funding Information

Supplement Formulators, Inc.
Vitamin D receptor and megalin gene polymorphisms are associated with longitudinal cognitive change among African‐American urban adults
Authors: Beydoun May A , Tajuddin Salman M. , Dore Gregory A , Canas Jose A , Beydoun Hind A , Evans Michele K. , Zonderman Alan B
Published: November 2023

Background

The link between longitudinal cognitive change and polymorphisms in the vitamin D receptor (VDR) and megalin genes remains unclear, particularly among African‐American adults.

Objectives

We aimed at evaluating associations of single nucleotide polymorphisms (SNP) for vitamin D receptor [VDR(1)rs11568820(CdX‐2:T/C); 2)rs1544410(BsmI:G/A);(3)rs7975232(ApaI:A/C);(4)rs731236(TaqI:G/A)] and Megalin[(1)rs3755166:G/A;(2)rs2075252:C/T;(3) rs2228171:C/T] genes with longitudinal cognitive performance change in various domains of cognition.

Design

Data from 660 to 797 African‐American urban adult participants in the Healthy Aging in Neighborhoods of Diversity Across the Lifespan were used. Latent class (LC) and haplotype (HAP) analyses were conducted creating gene polymorphism groups that were related to longitudinal annual rate of cognitive change (LARCC) predicted from mixed‐effects regression models.

Results

Among key findings, rs3755166:G/A megalin SNP was associated with faster decline on the Mini‐Mental State Exam overall (β=−0.002; p=0.018) and among women. VDR2 (BsMI/ApaI/TaqI: G‐/A‐/A‐) SNP latent class (SNPLC) (vs. VDR1 [ApaI:”AA”]) was linked to faster decline on verbal fluency‐category (VFT‐C) in women. Among men, Megalin2 (rs228171 “TT”) SNPLC (vs. Megalin1:rs228171: “CC”) was associated with faster decline on Trails B but slower decline on DS‐B. Moreover, among men, VDR1 SNPHAP (GCA:baT) was associated with slower decline on Trails B, while Megalin1 SNHAP (GCC) was associated with faster decline on DS‐B, reflected as faster decline on cognitive domain 2 (“visual/working memory and executive function”).

Conclusion

Sex‐specific VDR and Megalin gene variations can alter age‐related cognitive trajectories among African‐American urban adults, specifically in global mental status and domains of verbal fluency, visual/working memory and executive function.

Support or Funding Information

This research was supported entirely by the Intramural Research Program of the NIH, National Institute on Aging.
Neuroprotective effect of Rg5/Rk1 against thermal stress‐exposed damage of hippocampal cell line HT‐22
Authors: Choi Seo‐Yun , Song Ji‐Hyeon , Chei Sungwoo , Koh Eun‐Jeong , Choi Jia , Seo Young‐Jin , Park Min‐Ki , Hwang Ji‐Hyun , Lee Yeon‐Joo , Yang Byung Wook , Park Jong Dae , Lee Boo‐Yong
Published: November 2023

Environment thermal stress causes a number of physical and physiological problems including cognitive impairment. Thermal stress‐induced cognitive impairment might be the results of hippocampus neuronal damage. Although a number of reports considered phytochemicals as therapeutic ingredient for thermal stress, the detailed mechanisms by which phytochemical contribute to prevent thermal stress is still unclear. The aim of this study was to investigate the potential effect of ginsenoside Rg5/Rk1 in the treatment of thermal stress‐exposed hippocampal cell line HT‐22. Here, we observed that thermal stress (43 ºC) caused cell cycle arrest due to the activation of p21 and activation of PARP cleavage in HT‐22 cells, while Rg5/Rk1 retained the p21 expression as well as suppressed the PARP cleavage. In addition, thermal stress induced the aberrant expression of NF‐E2–related factor (Nrf2) and its downstream target heme oxygenase (HO)‐1. These attributes was significantly derepressed in thermal stress‐exposed HT‐22 cells with the presence of Rg5/Rk1. To determine the reactive oxygen species, we performed DCF‐DA staining. Image analysis revealed that Rg5/Rk1 attenuated the production of ROS in thermal stress‐exposed HT‐22 cells. We next observed that the phosphorylation of CREB and the expression of BDNF proteins dramatically decreased in thermal stress‐exposed HT‐22, while Rg5/Rk1 prevented the degradation of those proteins. Taken together, our findings suggest that thermal stress can lead to activation of hippocampal cell damage and reduction of memory‐associated molecules in the hippocampal cell line HT‐22. These finding also provide a molecular rationale for the role of Rg5/Rk1 as a potent cognitive impairment preventive compound in blocking the initiation of hippocampal damage.
1,25(OH)2D3 Protects SH‐SY5Y Human Neuroblastoma Through Decreasing Aβ Toxicity and Reducing Tau Protein Hyperphosphorylation
Authors: Liao Hsiang , Chang Yi‐Chen , Lin Shyh‐Hsiang
Published: November 2023

The accumulation of β amyloid (Aβ) and intracellular tau protein hyperphosphorylation in the brain are the major pathological features of Alzheimer's disease (AD), leading to neuron dysfunctions and brain cell apoptosis. Vit.D has been shown to promote cell survival through increasing the expression of GDNF. In this study, we investigated the preventive effects of 1,25(OH)2D3 on Aβ‐induced toxicity to SH‐SY5Y human neuroblastoma cells. 1,25(OH)2D3 was pre‐treated to the cells at concentrations of 0.1, 1, 10, and 100 nM 24 hours before 24 hours Aβ (1 μM) treatment. It was found that 1,25(OH)2D3 increased GDNF protein expression, activated the phosphatidylinositol 3 kinase/protein kinase B (PI3K/Akt) pathway and decreased cell tau protein hyperphosphorylation and apoptosis in SH‐SY5Y cells treated with Aβ after the 1,25(OH)2D3 pre‐treatment. In conclusion, 1,25(OH)2D3 showed potentials in protecting the detrimental effects caused by Aβ in neuronal cells.
Relationship between whole grain consumption and selective attention
Authors: Evensen Jackson , Edwards Caitlyn , Thompson Sharon , Holscher Hannah , Khan Naiman
Published: November 2023

Introduction

Greater habitual diet quality has been associated with weight regulation and reduced risk for chronic diseases including cardiovascular disease and Type‐2 diabetes. Previous studies have outlined the role of markers of diet quality ‐ wholegrain consumption in particular ‐ in reducing the risk for these diseases. However, the role of wholegrain consumption in cognitive function remains unclear. Studying these relationships may contribute to the body of literature linking whole grain consumption to improved physical and mental health.

Methods

Adults between 25–45 years (N=76, 32 males) reported their dietary intake using the National Cancer Institute's (NCI) Diet History Questionnaire II (DHQII). Overall diet quality was assessed using the Healthy Eating Index (HEI‐2010) and whole grain consumption was measured using the whole grain component of the HEI‐2010. Selective attention was assessed using a modified Eriksen flanker task. Overall intellectual ability (IQ) and whole body adiposity (%Fat) was measured using the Kaufman Brief Intelligence Test and dual energy x‐ray absorptiometry, respectively.

Results

Partial correlations were conducted to examine relationships between whole grain consumption and flanker task variables following adjustment of age, sex, IQ, and total HEI‐2010 score. Whole grain consumption was positively related to accuracy in the both the congruent (r=0.37, P<0.01) and incongruent task conditions (r=0.28, P=0.02). Further, although no significant relationships were observed for mean response time (all Ps> 0.26), greater whole grain component scores were related to lower intraindividual variability (coefficient of variation) in reaction time during the incongruent (r=−0.33, P<0.01) but not congruent condition (r=−0.18, P=0.13).

Conclusion

These data indicate that individuals with greater whole grain intake exhibited superior selective attention, as indicated by higher response accuracy and reduced variability in response time. Given that these relationships persisted even after adjusting for overall diet quality and important health and demographic factors provides support for the selective importance of whole grain intake for cognitive function. Future experimental studies are necessary to determine the impact of changes in whole grain intake on changes in cognitive function.

Support or Funding Information

Funded by the Department of Kinesiology and Community Health at the University of Illinois and the Hass Avocado Board.
Seedy Business: Adding Healthy Additives Transforms Indulgence to Health Food in Consumers' Minds
Authors: Tal Aner , Wansink Brian
Published: November 2023

This study explores whether adding healthy seeds to high‐calorie foods makes them appear healthier in consumers' evaluation. Adding healthy foods to a meal is known to affect calorie estimation (Chernev and Gal 2011). Here, we explore this effect on the ingredient level.

Participants (N = 111) were recruited on Amazon Mechanical Turk. Participants viewed six foods: muffins, croissants, cookies, carrot cake, peanut‐butter bars, and pancakes. Foods were all high‐calorie, and generally perceived as low healthiness. Participants rated calories (open measure) and healthiness (9‐point likert from not at all healthy to very healthy) in each food. For each food, half of the participants rated the food as is, and half with an added healthy ingredient included in the description. These included blueberries, flax‐seeds, brown‐sugar, carrots, hemp‐seeds, and quinoa, respectively. Flax seeds significantly improved healthiness ratings (p = .003) and calorie estimates (p = .02) of croissants. Similarly, hemp seeds significantly improved health ratings (but not calorie estimates) of peanut‐butter bars (p = .056). There were also borderline significant effects (.05< p <.1) for calorie estimates of cookies with brown sugar, healthiness of cake with carrots, and healthiness of pancakes with quinoa. For other foods, there were directional, though non‐significant, effects.

Ingredients perceived as healthy can generate health halos (Chandon and Wansink 2007; Wansink and Chandon 2006) and lead to healthier food evaluations. Seeds (Chia, Flax) appear to be especially effective at increasing estimated healthiness. This might operate regardless of the quantity of seeds added. These findings indicate a commercial strategy that may lead to adverse health effects, as adding healthy seeds can “health wash” a food, leading to increased consumption of foods that remain at basis unhealthy (Finkelstein and Fishbach 2010).
More of a Bad Thing: How Consumers Ignore Pollutant Levels
Authors: Tal Aner , Wansink Brian
Published: November 2023

Objective

Assess whether consumers neglect consideration of pollutant quantity in determining food healthiness. In the current work, we argue that consumers heuristically consider the mere presence of a harmful ingredient in making healthiness judgments. The mere presence of a harmful food ingredient generates an emotional impact that leads consumers to see an ingredient as unhealthy. Contrary to that, the quantity of a harmful pollutant may be neglected, as it does not factor in to its emotional impact.

Methods

Participants (N = 98 Mechanical Turk participants) evaluated the healthiness of a depicted apple said to contain pesticide. Participants were randomly divided into three groups. One group was not told the apple contained pesticide called Carbaryl. The second group was told the apple contained 7.4 microgram of pesticide, and the third group was told the apple contained 4200 microgram of pesticide. The rated the healthiness of the apples on 9 point likert scales anchored by not at all healthy and very healthy.

Results

There was a significant effect of pesticide on health evaluation: F(1, 98) = 18.94, p < .0001. Planned contrast revealed differences between presence and absence of pesticide: F(1, 98) = 37.88, p<.0001, but no difference between the different levels of pesticide: F(1, 98) = .03, p = .87.

Conclusion

Consumer assessment of the healthiness of foods containing pollutants acts in an all‐ or‐nothing manner, considering the presence of a pollutant, but not its level. Consumers display an insensitivity to the quantity of a pollutant in assessing product healthiness. This might result from their inability to discriminate between different levels of the pollutant, and the fact that most of its impact is an emotional outcome of its mere presence.
Limited Access to a Palatable High Fat Diet Promotes Binge‐Like Food Intake and Addiction‐Like Dopamine Terminal Adaptations in the Nucleus Accumbens Core of Mice.
Authors: Fordahl Steve , Jones Sara
Published: November 2023

Consumption of palatable food engages the mesolimbic dopamine system, and chronic exposure causes dopamine terminal adaptations that resemble changes observed with drug abuse. We previously reported that limited access (3d per week for 2hrs per day) to a high fat diet increased the behavioral response to repeated amphetamine (AMPH) exposures. Increased behavioral sensitization was accompanied by elevated dopamine transporter (DAT) protein content in the cytosol, compared to the plasma membrane, and attenuated DAT function in the nucleus accumbens core (NAc). The current study examined whether acute AMPH exposure redistributes the DAT from the cytosol to the membrane, thereby increasing AMPH potency at dopamine terminals, and putatively augmenting behavior. We show in C57BL/6 mice that limited access to high fat caused binge‐like intake during the first 30 mins of access, which increased from 27% to 48% of their daily kcals over the 6‐week period, a behavior similar to escalated intake of self‐administered drugs or alcohol. After six weeks of limited high fat exposure, mice were then given intraperitoneal AMPH (0.5 mg/kg) one hour before slice voltammetry experiments to characterize dopamine terminal changes in the NAc. Compared to chow‐fed control mice, binge‐like intake of high fat reduced basal dopamine uptake (−0.67 μM/sec, Vmax), attenuated AMPH potency (−5.8 μM, Km), and enhanced dopamine D2/D3 autoreceptor sensitivity to quinpirole (−9.22 nM, IC50). Acute AMPH, however, significantly increased basal dopamine reuptake in high fat bingeing mice (+2.05 μM/sec, Vmax), but not control mice (+0.21 μM/sec, Vmax), and significantly increased AMPH potency at the DAT (+7.6 μM, Km), as well as D2/D3 autoreceptor sensitivity to quinpirole (−4.55 nM, IC50) to more closely resemble control mice. Our data suggest that acute AMPH improves dopamine terminal deficits following binge‐like high fat intake, possibly by redistributing the DAT to the plasma membrane. These findings align with previous reports showing AMPH potency is linked to DAT density. Overall, binge‐like intake of a high fat diet reduces dopamine terminal function, which can be reversed by acute AMPH. A significantly larger shift in AMPH potency compared with controls, coupled with reduced D2/D3 sensitivity, may contribute to the enhanced behavioral response to AMPH we observed previously using this binge‐feeding paradigm.

Support or Funding Information

(SCF) T32AA007565, P50DA006634 Pilot Grant

(SRJ) AA0014091, AA021099, DA021325, DA030161 and DA006634
Dietary Fatty Acids and Associated with Anxiety and Depression in Older Adults
Authors: Luo Jing , Chai Sheau C , Arjmandi Bahram H
Published: November 2023

It is estimated that approximately 11–20 percent of older adults in the United States suffer from some form of mental disorder, such as anxiety and depression. Studies have shown that dietary factors can reduce cognitive and emotional symptoms. Numerous studies also support a relationship between the intake of dietary fatty acids and a decreased risk of developing dementia. However, the effects of different dietary fatty acids on emotional symptoms in older adults remain unclear. A cross‐sectional study was conducted that included 128 men and women aged 65–80. Individuals taking any medications that may influence brain function or diagnosed with dementia or any neurological disorders were excluded. Dietary intake was assessed using a Block Food Frequency Questionnaire. Depression and anxiety were assessed using Geriatric Depression Scale (GDS) and Geriatric Anxiety Inventory (GAI). Statistical analyses were performed using SPSS. Partial Pearson correlations and multiple regression analyses were conducted to examine the association between different intake of fatty acids and emotional status. Our findings indicate that total trans fat was positively correlated with GAI score (r=0.206; p=0.002). Intake of dietary n‐3 PUFA 18:4 (Stearidonic acid) (r= −0.233; p=0.010), dietary n‐3 PUFA 20:5 (Eicosapentaenoic acid) (r= −0.220; p=0.014), dietary n‐3 PUFA 20:6 (Docosahexaenoic acid) (r= −182; p=0.044), and dietary n‐3 PUFA 22:5 (Docosapentaenoic acid) (r= −0.212; p=0.018) were inversely associated with GDS score. Results from multiple regression, after adjusting for gender, income, body mass index, education, and total calories, indicate that total trans fat was positively associated with GAI score (p=0.007; b= 0.236). Intake of dietary n‐3 PUFA 18:4 (p=0.010; b= −0.226) was inversely associated with GDS score. Findings suggest a need for reduced intake of trans fat and increased intake of n‐3 PUFA 18:4 to reduce the risk of developing anxiety and depression among older adults.