bluuebunny/crossref_metadata_2025 huggingface dataset:
Duplex Ultrasound Measuring Hemodynamic Variations of the Superior Mesenteric Artery in Pre‐ and Postprandial Subjects: Understanding Mesenteric Ischemia
Authors: Elnekaveh Brandon Mordeccai , Adar Tony , Baral Sumit , Pagano Anthony , Belyayeva Irina , Marquez Samuel
Published: June 2021

Mesenteric ischemia (MI) is characterized by disabling postprandial abdominal angina stemming from hypoperfusion of the midgut due to inadequate vascular compensatory mechanisms in the superior mesenteric artery (SMA). Duplex ultrasound was used to measure the vascular diameter, peak systolic velocity (PSV), and end diastolic velocity (EDV) of the SMA in 6 healthy subjects after an overnight fast and 30 minutes after eating. Results show a preprandial PSV range of 100.3 – 123.2 cm/s and DV of 18.0 – 26.7 cm/s, and a postprandial PSV of 194.9 – 246.5 cm/s and EDV 41.1 – 73.7 cm/s. All subjects experienced significant increases in SMA postprandial blood velocities (p<.05) with only a slight increase in its diameter (p>.05). In the fasting state, early diastolic flow reversal was observed, yet it was absent postprandially. Normal SMA flow is characterized by a high‐resistance outflow bed in the fasting state. These data suggest that postprandial abdominal pain in MI may indeed be related to increased mesenteric blood flow met by an inadequate vascular response resulting in tissue ischemia.

Grant Funding Source: Alumni Association
Mice and rats have different responses to abdominal aorta constriction
Authors: Prado Cibele M. , Blefari Valdecir , Ribeiro Mayara S. , Celes Mara RN , Freitas Ana CS , Malvestio Lygia M , Campos Erica C , Ferezin Patricia , Jelicks Linda A , Tanowitz Herbert B , Rossi Marcos A
Published: June 2021

Background

Constriction of the abdominal aorta just below the diaphragm is postulated as an experimental model of pressure overload cardiac hypertrophy. The increased blood pressure proximal to the constriction works as a stimulus for the development of cardiac hypertrophy. The objective of this study was to compare different degrees of abdominal aortic constriction in mice and rats in relation to the production of cardiac hypertrophy.

Material/Methods

C57BL/6 and Swiss mice and Wistar rats were used. The aorta was constricted with a ligature of 6.0 silk (mice) or 4.0 cotton (rats) thread around the probe, which was immediately removed after the constriction. Different calibers of probes were used to produce different degrees of constriction. The animals were killed 30, 45, 60 and 75 days post surgery (dps) and the aorta and hearts collected.

Results/Conclusions

Mice=the probes 0.50 and 0.45 mm produced 65% and 68%, respectively, of aorta constriction and produced hypertrophy only at 60 and 75 dps. The probe 0.40 mm produced 80% of constriction and produced hypertrophy only at 45/60/75 dps. The probe 0.30 mm killed all the animals 24h after surgery. Rats=the probes 0.80 and 0.70 mm produced 71% and 80%, respectively, of constriction and produced hypertrophy after 30 dps. Mice are more resistant and need more time to develop cardiac hypertrophy as compared to rats when submitted to abdominal aorta constriction.

Grant Funding Source: FAPESP, CNPq, FOGARTY
Immunohistochemical localization of PACAP and VIP receptors in major salivary glands and the effect of PACAP on saliva secretion in mice
Authors: Nonaka Naoko , Nakamura Masanori
Published: June 2021

The control of saliva secretion is mainly under the autonomic nervous control. Pituitary adenylate cyclase‐activating polypeptide (PACAP) is now recognized as the multi‐functional neuropeptide in various organs. Vasoactive intestinal polypeptide (VIP) is similar function to PACAP. In this study, we compared the distribution of PACAP receptor, PAC1R and VIP receptor, VPAC1, in major salivary glands; parotid, submandibular and sublingual glands, and examined the effect of PACAP on saliva secretion in 8 weeks old C57BL/6 mice. In parotid gland, PAC1R and VPAC1 were detected in the cells of striated duct. In the case of submandibular gland, PAC1R and VPAC1 were detected in the tall columnar epithelial cells, called pillar cells, in granular ducts and some of the cells in the striated ducts. In sublingual gland, PAC1R and VPAC1 were expressed mainly in the epithelial cells of striated ducts. Intranasal injection of PACAP enhanced the secretion of saliva. Taken together, these results indicated that the distribution of PAC1R and VPAC1 were similar in three major salivary glands and that PACAP and VIP might be the useful agents for the future dry mouth therapuutics.
Autotaxin, a potent inducer of cell motility and differentiation, is differentially expressed in visceral and parietal mesothelia
Authors: Shelton Elaine L. , Hong Charles C. , Bader David M.
Published: June 2021

The serosal mesothelium is a simple squamous epithelium lining the body cavity. It can be divided into two categories: visceral mesothelium covering abdominal organs including the omentum and parietal mesothelium lining the peritoneal wall. Earlier investigations considered visceral and parietal mesothelia the same cell type. Indeed, these tissues are continuous and share similar expression of mesothelial marker genes. However, we report a microarray analysis of murine visceral and parietal mesothelia where over 35,000 genes were differentially expressed. Specifically, Autotaxin (Atx) was expressed significantly higher in visceral versus parietal mesothelium. Atx is a secreted glycoprotein that is responsible for production of Lysophosphatidic acid (Lpa), promotes cell motility, cell survival, and angiogenesis, and has been identified as an important mediator of tumorigenesis. Here, we demonstrate visceral mesothelium migrates and differentiates into smooth muscle more readily than parietal mesothelium. Addition of Atx to parietal cells induces “visceral‐like” migration and differentiation. Finally, we identified several novel small organic molecule inhibitors of Lpa that repress Atx‐induced motility and differentiation. Importantly, as Atx plays a critical role in tumorigenesis, these inhibitors may represent new therapeutic agents for a variety of cancers including mesothelioma.

Grant Funding Source: NIH
A Novel Staging System to Assess the Severity of Colorectal Polyposis in Patients with FAP
Authors: Lu Zhen Arthur , Hawk Ernest , Lynch Patrick , Patterson Sherrie
Published: June 2021

Familial Adenomatous Polyposis (FAP), a genetic disease that primarily affects the gastrointestinal tract, is caused by a mutation in the Adenomatous Polyposis Coli (APC) gene. One of the hallmarks of this disease is the formation of benign outgrowths known as polyps on the linings of the large intestines and rectum. Although non‐malignant, early presentation of polyps in the colon have been shown to increase the risk of colon cancer by the age of 40 to nearly 100%. As a result, surgeons have traditionally opted to remove the affected colon and/or rectum in an attempt to mitigate the morbidity and early mortality associated with FAP. With the availability of mutational testing and genetic counseling, patients suspected of having FAP are being monitored much earlier on than before. The presence of a known APC mutation can be detected when the patient is as young as 10 – 14 years old. This, coupled with a deeper understanding of genetics, disease progression, and chemo‐interventions such as omega‐3 and COX‐2 inhibitors provides clinicians with a better arsenal of adjunctive care strategies besides surgery to manage the disease. Progressively, patients and their families have opted to defer or, ideally, prevent surgery for the sake of psychological effects and the maturity of the patient at the time of diagnosis. Therefore, it becomes necessary to establish a universal staging system to assess the disease severity of FAP in the colon and rectum so that both doctors and patients can objectively monitor the disease progression to decide upon the most effective and appropriate treatment strategies. Disease severity will be quantified by a numerical from 0–4 depending on the quantity and size of the polyps. Based off the objective score, a specific treatment will be prescribed with surgery for the most severe cases, and routine check‐up for more moderate cases.

Grant Funding Source: AAA
Protective effect of tetramethylpyrazine (TMP) on autosomal dominant polycystic kidney disease (ADPKD)
Authors: ran jianhua , He Guiqiong , Sun Shanquan
Published: June 2021

The study investigated the inhibited effect and possible mechanism of tetramethylpyrazine (TMP) on cyst development of autosomal dominant polycystic kidney disease (ADPKD) in vitro. The Madin‐Darby Canine Kidney (MDCK) cell cyst model was established to evaluate the inhibition activity of drug. Cell cytotoxicity and proliferation were detected by MTT assay and Cell Counting Kit (CCK) assay. Ras/MAPK signaling pathway‐related proteins was examined by Western blot. Results showed that the cyst inhibition of tetramethylpyrazine (IC50=0.158 ¦ÌM) with dose‐response relationship. Tetramethylpyrazine prevented forskolin‐promoted MDCK cell abnormal proliferation mainly by decreasing expression of B‐Raf and increasing expression of Raf‐1 to regulate level of p‐ERK at testing concentrations with no apparent toxicity. These results suggest that tetramethylpyrazine might be developed as novel candidate drugs for the treatment or mechanism study of ADPKD.

Supported by the National Natural Science Foundation of China (30500171), and the Natural Science Foundation of Chongqing (CSTC2010BB5098).
Satellite cell pool size expansion is affected by skeletal muscle characteristics
Authors: Macaluso Filippo , Brooks Naomi E , Niesler Carola U , Myburgh Kathy H
Published: June 2021

The purpose of this study was to determine the change of satellite cells (SC) pool size after an acute bout of strenuous exercise and to determine whether this is affected by baseline SC count and fiber type.

Participants completed 40min (5 × 8 bouts, 2 min rest) downhill running (DHR) at 80% VO2max at −10% gradient. Muscle biopsy was taken a week before VO2max test and 7–9 days after DHR. Delayed onset muscle soreness (DOMS) and creatine kinase activities (CK) were measured on d1, d2 d7, and d9 after the DHR bout. Satellite cells were analyzed with Pax7 and laminin immunohistochemistry staining.

DOMS and CK increased 1 day after DHR (P < 0.01) and returned to baseline. SC pool size was increased by 26% 7–9 days after the exercise intervention (P = 0.005). SC count after the acute exercise intervention was significantly correlated with VO2max (P = 0.03). A trend was seen in correlation between change in SC and percentage MHC type II (P = 0.10).

This study reports that 7–9 days after a single bout of DHR, the SC pool expands and the expansion extent is associated with inter‐individual physiological characteristics: VO2max and with a tendency, skeletal muscle fiber type.

Grant Funding Source : Claude Leon Foundation, NRF (National Research Foundation)
Transient exposure to hydrogen peroxide inhibits degradation of phosphorylated IκBα
Authors: Lee Yeji , Choi Jin , Jue Dae-myung
Published: June 2021

NF‐κB is a family of transcription factors involved in many cellular functions, such as cell survival, proliferation, chronic inflammation, and stress responses. Reactive oxygen species(ROS) has been implicated as a modulator of NF‐κB activity in various cell types. However the effect of ROS on NF‐κB is controversial. We studied the effect of transient oxidative stress on TNFα‐induced NF‐κB activation in HEK293 cell. Transient exposure of H2O2 caused significant decrease in expression of NF‐κB reporter gene, 15~30 min delay of IκBα degradation and p65 nuclear translocation, but had no effect on IκBα phosphorylation and IκB kinase activity. Expression of NF‐κB reporter gene induced by TNFα was also delayed by H2O2 with a lag of 3 hr compared with TNFα‐stimulated control cell. Our results showed that transient exposure to oxidative stress inhibits degradation of phosphorylated IκBα while it does not modulate IκB phosphorylation by IκB kinase.

This research was supported by Basic Science Research Program through the National Research Foundation of Korea(NRF) funded by the Ministry of Education, Science and Technology(2011‐0024179)
A New Role for the Proofreader in Bacterial DNA Replication
Authors: Dixon Nicholas E. , Jergic Slobodan
Published: June 2021

The DNA polymerase III holoenzyme (Pol III HE), the E. coli chromosomal replicase, is made up of 2 (or 3) αεθ core polymerases, 3 dimeric β sliding clamps, and the 7‐subunit clamp loader that loads the clamp onto primer‐templates. When bound to the clamp, the Pol III core becomes fast (~750 nt/s) and processive (>50 kb) due to the α‐β interaction. The ε subunit is the proofreading 3′→5′ exonuclease that interacts with α and greatly increases the fidelity of Pol III HE. Genetic studies 20 years ago suggested that ε has an essential role in replication beyond its contribution to fidelity, and we have previously also shown that it is attached to α via a flexible linker that permits it to sample a relatively large space around α in the replicase. Here, we present new functional assays (Pol III strand displacement and primer extension under difficult conditions) that expose the additional role of ε in DNA replication. Bioinformatics indicated it may be mediated by a new interaction with the β clamp. We further utilized SPR and ESI‐MS to obtain direct evidence for a physical interaction between ε and β both in isolation and within the Pol III‐clamp complex. Single molecule DNA replication assays revealed the role of the relatively weak yet important ε‐β contact in stabilization of the polymerase on the DNA template.
Investigating the Effect of the Oligopeptide Repeat Region on Prion Propagation
Authors: Langlois Christine , Serio Tricia
Published: June 2021

Prions are proteins that can adopt distinct conformations in vivo: a native form and a collection of misfolded or prion forms, which alter the activity of the protein. Remarkably, the prion forms self‐replicate their structure by assembling into ordered aggregates, which template the conversion of the native form into a like state and allow the associated phenotypes to persist. This process of self‐replication is dictated by the sequence of the prion protein. For example, the Sup35 prion in S. cerevisiae has a bipartite prion domain containing a poly‐glutamine‐rich element and five and a half imperfect repeats of a nonapeptide, which are both required for prion propagation. The polyglutamine region mediates templating, but the function of the repeats is currently unknown. Our studies suggest that the steady‐state size of prion aggregates decreases as repeat number increases, and these effects are exacerbated by the deletion of a newly identified sequence element proximal to the repeats. Intriguingly, changes in aggregate size in either direction decreases the abundance of heritable prion aggregates. Together, our studies suggest that the repeat and proximal regions fine‐tune the process of conformational self‐replication through a change in prion aggregate dynamics to create a protein‐based epigenetic element. Supported by NIH 1F31GM099383‐01.
HSP90 Interaction with eNOS and nNOS
Authors: Ghosh Dipak Kumar , Chrestensen Carol , McMury Jonathan L , Salerno John C
Published: June 2021

HSP90s are multi‐function chaperonins expressed at high levels in mammalian cells; homologues are important in most eukaryotes. HSP90s have a broad range of client proteins, and have been implicated in protein folding, and many proteins are stabilized by interaction with HSP90. HSP90 recognizes early stages denaturation and prevents the formation of large aggregates, allowing clients to regain native conformation. The HSP90‐client complex also includes the P23 co‐chaperone, a small heat shock protein. Binding is ATP independent, but HSP90 has significant ATPase activity connected with client release.

Binding of eNOS and nNOS to HSP90 can be observed using interferometric methods. Both eNOS and nNOS bind to immobilized HSP90 with moderate affinity (~200–500 nmolar). Both isoforms have a complex report of binding. Above Kd, both bind with near diffusion limited rates, and both show a second slow phase during which the shift of the interference pattern is significantly reduced, implying either release or a major conformational change while bound to the sensor. HSP90 is a potent activator of both cytochrome c reduction and NO synthesis in both isoforms. This can be explained at the molecular level by changes in population of enzyme conformations. eNOS and nNOS have three major FMN fluorescence lifetime states corresponding to FMN‐FAD, FMN‐heme, and essentially non interacting configurations. Like calmdodulin, HSP90 releases the FMN binding domain from a tight complex with the dehydrogenase domains of NOS, promoting the longer lived states at the expense of the short lived (90ps) FMN‐FAD pair of the input state. HSP90‐NOS interactions revealed via fluorescence exhibit temporal fluctuations reminiscent of the complex report of binding, and are responsive to ATP.
The JAK kinase Tyk2 and the Signal Transducer and Activator of Transcription 3 (Stat3) are required for Brown Adipose Tissue Differentiation
Authors: Larner Andrew Charles , Derecka Marta , Gornicka Agnieszka , Szczepanek Karol , Morgan Magdalena , Raje Vidisha , Sisler Jennifer , Keller Susanna
Published: June 2021

Type II diabetes, cardiovascular disease, non‐alcoholic fatty liver disease and Alzheimer's disease are some of the numerous disorders associated with the obesity epidemic. Two functionally different types of fat that maintain energy balance contribute to the development of obesity. White adipose (WAT) is the primary site of energy storage, and brown adipose tissue (BAT) is responsible for energy expenditure in a process termed thermogenesis.

We have made the novel observations that mice which do not express the Jak tyrosine kinase Tyk2 become obese with age, and Tyk2 is required for BAT differentiation. In addition to Tyk2, expression of the constitutively active form of the transcription factor Stat3, (CAStat3) restores BAT differentiation and the expression of BAT‐specific genes in Tyk2−/−‐preadipocytes as well as Tyk2−/− mice that express CAStat3 in BAT. In contrast, disruption of Stat3 expression in Tyk2+/+ preadipocytes prevents proper development of brown adipocytes

Expression of CEBP/B and PRDM16, a master‐regulator of BAT differentiation, restores BAT differentiation in Tyk2−/− preadipocytes. Consistent with the observation that Stat3 and PRDM16 form a complex with C/EBPB□ Stat3 is also required for CEBP/B and PRDM16 mediated differentiation of brown adipocytes.. These studies define a novel role for the tyrosine kinase Tyk2 and Stat3 as determinants of brown fat‐lineage.
The redirection of adipocyte to osteoblast through the alteration of the Casein Kinase 2 interaction with the Bone Morphogenetic Protein 2 Pathway
Authors: Gurski Lauren Marie , Bragdon Beth , Nohe Anja
Published: June 2021

Osteoporosis is a degenerative disorder resulting in the loss of bone mass over time with the replacement of fat. Bone Morphogenetic Protein 2 (BMP2) is a growth factor that promotes the differentiation of osteoblasts and adipocytes. Casein Kinase 2 (CK2) interacts with BMP2 receptor Ia (BMPRIa) at three phosphorylation sites. When CK2 is prevented from binding to one of its sites on BMPRIa with the use of a CK2 blocking peptide, the pathway promotes the differentiation of a particular cell. When peptide CK2.2 is used to stimulate cells differentiating the stem cells into both adipocytes and osteoblast then several days later stimulated again with CK2.3 we see a decrease in adipocyte and an increase in osteoblast in comparison to the controls only stimulated with either peptide alone. This difference suggests a redirection from adipocytes to osteoblasts caused by CK2.3. To find further evidence for a redirection, cells were cultured out of three types of mice: a high bone density mouse (1–12), a low bone density mouse (6T), and a control mouse (B6). Each type of cell was stimulated with CK2.3 and a series of controls. The amount of mineralization and adipogenesis was then determined.
The influence of advanced age on novelty detection
Authors: Ferng Jonathan J. , Burke Sara N. , Hartzell Andrea L. , Friel Jacqueline M. , Barnes Carol A.
Published: June 2021

Aged rats are impaired at object recognition because they identify novel objects as familiar. The extent to which this impairment can be explained in terms of object discrimination deficits, or a decreased ability to detect novelty has not been described. Previous studies have suggested that a functionally intact noradrenergic system is necessary to facilitate novelty detection. The main source of noradrenaline in the brain, the locus coeruleus (LC), experiences morphological changes with age. The current experiment tests the hypothesis that these structural changes may partially account for the inability of aged rats to correctly identify novel objects. Young (9 months) and old (24 months) rats were placed in a hole board apparatus for a habituation and object phase separated by a 3‐hour period. The 9 holes of the hole board were left empty for the habituation phase while 4 of the holes were filled with 4 identical objects in the object phase. Novelty detection was quantified by comparing the number and duration of nose pokes in holes with objects relative to the holes without objects. There was no significant difference in the performance of young and old animals, implying that age‐related changes in LC neurons do not functionally impact novelty detection. This research was supported by the Howard Hughes Medical Institute ‘06 Grant (#52005889) and the McKnight Brain Research Foundation at the University of Arizona.
Prostate Cancer Pathways: Selective Action of 2‐ Methoxyestradiol
Authors: Ellis Jeffrey Lee , Hopkins Nancy Eddy
Published: June 2021

The objective of this study is to investigate analyze the mechanism of an anti‐cancer drug, 2‐methoxyestradiol. The drug will be applied to PC‐3 prostate cancer cells. This project will look at two proteins in the apoptotic pathway 2‐methoxyestradiol selectively phosphorylates through various Western blotting assays. This study aims to examine ways to improve efficacy and minimize potentially harmful side effects of 2‐methoxyestradiol.
MARCO modulates asbestos‐induced Rac1 mitochondrial import and H2O2 production
Authors: Murthy Shubha , Kobzik Lester , Carter A Brent
Published: June 2021

Rac1 is a second messenger involved in many cellular processes, including the production of H2O2. Our previous observations demonstrate that macrophage Rac1 activation is crucial for the development of pulmonary fibrosis, and Rac1 localizes to the mitochondria in asbestosis patients. Asbestos induced Rac1 translocation to the mitochondria and mediated H2O2 production. The mechanism by which asbestos activates Rac1 is not known. The macrophage receptor with collagenous structure (MARCO) has been shown to provide innate immune defense against inhaled particles and pathogens. We, therefore, hypothesized that MARCO binds asbestos and modulates Rac1 import into the mitochondria and mitochondrial H2O2 production. Both the total and cell surface expression of MARCO was greater in macrophages from asbestosis patients compared to normal subjects. To address if MARCO modulated Rac1 import, we silenced MARCO and found that it resulted in reduced Rac1 mitochondrial localization. Furthermore, inhibition of ligand binding of MARCO dramatically decreased chrysotile‐induced mitochondrial H2O2. These results suggest that MARCO binds asbestos and, together with Rac1, is involved in upstream signaling events leading to asbestos‐induced mitochondrial H2O2 production. This work was supported by NIH grants ES015981 and ES014871 and Merit Review from Department of Veterans Affairs.
Identification of target proteins of shear stress‐related miRNAs in endothelial cells
Authors: Park Yoonsun , Kang Dong-Hoon , Son Dongju , Jo Hanjoong , Kang Sang Won
Published: June 2021

Atherosclerosis is an inflammatory disease that occurs preferentially at particular areas of disturbed flow characterized by low and oscillatory wall shear stress (OS) in branched or curved arteries. In contrast, straight arterial regions are exposed to high and stable laminar shear stress(LS) and are well protected from atherosclerosis.

To understand the molecular mechanisms by which shear stress elicits proatherogenic phenotype, we have performed miRNA microarray using in vitro cone and plate model and in vivo mouse partial carotid artery ligation model. As a result, we identified miR663 and miR712 wasas the most induced miRNAs in Human umbilical vein endothelial cells(HUVECs) and mouse aortic endothelial cells(MAECs).

Furthermore, we employed 2D‐DIGE in order to identify the target genes that are regulated by shear sensitive miR663 and miR712. As a result, in HUVECs, we were able to find 4 spots from soluble fraction(S‐100), and 3 spots from heavy membrane(HM) fraction, and 2 spots from light membrane(LM) fraction, which were downregulated upon pre‐miR 663 overexpression by minimum fold of 1.2. And in MAECs we found 4 spots from HM fraction which were upregulated upon anti miR712 LNA by minimum fold of 1.2. The proteins were analyzed further by mass spectrometry.

Therefore the proteomic technology allowed as to identify novel targets of miRNA in endothelial cells.
Specific O‐GlcNAcylated Peptide Enrichment with Improved Photocleavable Chemical/Enzymatic Tagging Methodology
Authors: Han Guanghui , Ma Junfeng , Liu Xin , Hart Gerald W.
Published: June 2021

Like phosphorylation, the addition of O‐linked beta‐N‐acetylglucosamine (O‐GlcNAcylation) which modifies serine and threonine residues on nuclear and cytoplasmic proteins is a ubiquitous, reversible process that regulates numerous cellular processes. Although several methods exist for the enrichment and identification of protein O‐GlcNAcylation sites, developing more sensitive enrichment methods are advantageous. Previously, we reported one very powerful methodology for the enrichment and characterization of O‐GlcNAc sites from complex samples: O‐GlcNAcylated peptides are tagged with a biotinylation reagent, enriched by affinity chromatography, and then released from the solid support by photochemical cleavage. Here, an improved method was reported by optimizing reaction conditions and more sensitivity was achieved by using less enrichment steps. The sensitivity of the improved method was demonstrated by selective enrichment of O‐GlcNAcylated peptides from mixture of tryptic digests of alpha‐crystalline and bovine serum albumin (BSA) at ratio of 1 to 1000 by LC‐MS/MS analysis. We are further applying this improved method to identify the O‐GlcNAcylation sites from proteins in prostate cancer cells.
Differential effects of radio frequency magnetic fields in vitro and in vivo
Authors: Martino Carlos F , Portelli Lucas , Ackerman Gail , Barnes Frank
Published: June 2021

Differential effects of RF magnetic fields in vitro and in vivo

Background

The present study investigates effects of radio frequency (RF) magnetic fields in the range 1–15 MHz on growth of cancer cells in vitro and in mice models. Most biomolecules have hyperfine splitting constants ranging from 0.1–10 MHz, which gives the basis for the chosen frequencies.

Methods

For in vitro experiments, fibrosarcoma cell line was treated 15 minutes a day with a combination of magnetic fields: 45 μT static fields in perpendicular and at 40 degrees to an RF signal. The exposures to an RF signal ranging from 5–10 MHz were conducted at a specific absorption rate (SAR) of 0.001, 0.01, 0.05 and 0.2 W/kg using continuous waves (CW). For in vivo experiments, mice with fibrosarcoma and pancreatic tumors were exposed continuously to low‐level static magnetic fields (0.5–2 μT) and a combination of 45 μT static fields in perpendicular to 10 MHz. All controls were exposed to the geomagnetic field (45 μT).

Results

A growth response curve as a function of SAR level is obtained indicating distinct effects for the SAR range used: inhibition of cellular proliferation is obtained for SAR level of 0.001 W/kg; SAR levels of 0.05 and 0.2 W/kg enhances proliferation in vitro. In vivo, 10 MHz magnetic fields inhibit tumor growth in mice as much as 35 percent on day 18 of exposure.

Conclusion

We have shown that even a physically weak magnetic field can alter cellular growth. RF magnetic fields modulated proliferation of cancer cells both in vitro and in vivo. The exposure levels were below standard threshold levels for thermal effects due to electromagnetic radiation.
Omega‐3 Fatty Acids Cause Dramatic Changes in TLR‐4 and Purinergic Eicosanoid Signaling in Macrophages
Authors: Norris Paul , Dennis Edward
Published: June 2021

Dietary fish oil omega‐3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), elicit cardioprotective and anti‐inflammatory effects through unresolved mechanisms. EPA and DHA may reduce arachidonic acid (AA) metabolism and pro‐inflammatory effects by competition and inhibition at multiple levels. Here, we report the effects of AA, EPA, and DHA supplementation on membrane incorporation, phospholipase A2 release, and eicosanoid production in RAW264.7 macrophages. Each PUFA supplemented increased by similar amounts in membrane phospholipids, while half of the increased AA and EPA were elongated to adrenic acid (AdA) and docosapentaenoic acid (DPA), respectively; and were subsequently released by PLA2 at levels comparable to AA. TLR‐4 stimulated COX‐2 AA production did not increase with AA supplementation and was inhibited by 20% and 50% after EPA and DHA supplementation, respectively. ATP stimulated COX‐1 AA production was inhibited to a greater extent by EPA and DHA; 5‐LOX AA metabolites increased 2‐fold with EPA and DHA supplementation, and 5‐LOX metabolized EPA and DHA to a greater extent than COX‐1/COX‐2. Altogether, AA, EPA and DHA supplementation decreased TLR‐4 stimulated AA COX‐2 prostanoid metabolism; increased the purinergic stimulated AA 5‐LOX/COX‐1 ratio; and significantly increased elongated PUFA levels that may be converted to novel mediators.
Role of DNA methylation in the regulation of lipogenic gene expression in the mouse neonatal liver
Authors: Kamei Yasutomi , Ehara Tatsuya , Takahashi Mayumi , Yuan Xunmei , Kanai Sayaka , Tamura Erina , Tanaka Miyako , Yamazaki Tomomi , Ezaki Osamu , Suganami Takayoshi , Okano Masaki , Ogawa Yoshihiro
Published: June 2021

The liver is a major organ of lipid metabolism, and the regulation of hepatic lipogenic gene expression in early life is largely unknown. Here, we show that expression of glycerol‐3‐phosphate acyltransferase 1 (Gpat1), a rate‐limiting enzyme of de novo lipogenesis, is regulated in the mouse liver by DNA methylation. In the mouse neonatal liver, DNA methylation of the Gpat1 promoter, containing binding sites for the lipogenic transcription factor SREBP1c, is high and its mRNA level is low, whereas the levels of DNA methylation and mRNA are low and high, respectively, in the adult. Chromatin immunoprecipitation analysis revealed Dnmt3b, a de novo DNA methyltransferase, but not SREBP1c, to be recruited to the Gpat1 promoter in the neonatal liver, whereas SREBP1c to be recruited in the adult liver. Maternal overnutrition causes the decreased Gpat1 promoter methylation with increased GPAT1 expression and triglyceride content in the liver, suggesting that environmental factors such as nutritional conditions, can affect DNA methylation and lipogenesis in the liver. This study is the first detailed analysis of the DNA methylation‐dependent regulation of lipogenic genes, thereby providing new insight into the molecular mechanism underlying the epigenetic regulation of metabolic genes, and thus metabolic diseases.
Nutritional Status for less‐explored micronutrients in underprivileged Guatemalan preschool children: Vitamin B12
Authors: Hernández Liza , Solomons Noel W , Romero-Abal María-Eugenia , de María Gamero Flor , Paul Ligi , Selhub Jacob , Bonorden Melissa J.L. , Herreid Richard M.
Published: June 2021

Background

Iron, vitamin A, iodine, zinc and folate are prominent on the public health nutrition agenda. Marginal or deficient vit B12 status was reported in 68% of peri‐urban Guatemalan lactating mothers and 49% of the infants.

Objective

To assess vit B12 status in a convenience sample of 3–6 y/o preschoolers in disadvantaged urban and rural communities receiving subsidized meals.

Methods

104 serum samples were obtained from boys and girls in 3 sites in the Central Highlands of Guatemala, 47 from 2 urban (U) centers and 57 from a rural (R) center. Circulating levels of vit B12 were measured by a chemiluminescent enzyme immunoassay method (Immulite 1000, Siemens, IL). Respective cutoff criteria for deficient and marginal for vit B12 were <200 pg/mL and 200–300 ng/mL. The contribution of dietary vit B12 from center menus was estimated.

Results

Overall mean vit B12 concentration (pg/mL) was 459±271 (median: 357): 583±294 (median: 527)(U) and 339±181 (median: 289)(R) (p<0.001). Globally, 8.6% had deficient and 26.9% had marginal values, for a 35.6% subnormal prevalence. Deficient plus marginal rates by setting were 10.6% (U) and 56.0% (R), respectively, with all 9 deficient subjects of rural origin. The 1 or 2 meals offered by the centers provided averages of 0.15 – 1.50 μg vit B12/d.

Conclusion

Slightly over one‐third of preschoolers had low vit B12 status, with a marked excess of low status in the rural setting.
Hepatic Effect of Quercetin in Rats Fed High‐Fructose Diet
Authors: Kim Jung-In
Published: June 2021

It has been reported that rats fed high‐fructose diet can be a suitable model for non‐alcoholic fatty liver disease. The purpose of this study was to investigate the preventive effect of quercetin against hepatic steatosis induced by a high‐fructose diet in rats. Male Sprague Dawley rats weighing 120–150 g were fed either a cornstarch‐based (60%), high‐fructose (60%), or high‐fructose (59.9%) diet with 0.1% quercetin for 10 weeks. Animals were sacrificed after an overnight fast. Serum adiponectin levels were measured. Liver lipids were extracted and levels of total lipids and triglycerides were measured. Serum adiponectin levels of fructose group were significantly lower than the control group (p<0.05). Consumption of quercetin significantly increased serum adiponectin levels compared with fructose group. Hepatic total lipids and triglyceride levels were significantly increased by the high‐fructose diet compared to the controls, while these parameters were significantly reduced by consumption of quercetin. These results indicate that quercetin could alleviate hepatic steatosis in fructose‐fed rats. This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2009‐0068845).
Effects of Mungbean extract and Mungbean tesa extract on adipogenesis and obesity‐related inflammation in vitro 3T3L1 cells and in vivo KK‐Ay mice
Authors: Kang Inhae , Chang E , Yang SJ , Quan ZJ , Park MY , Choi MJ , Kim JI , Wi HR , Choi SL , Lee M
Published: June 2021

Obesity is associated with increased metabolic diseases such as hyperlipidemia, type2 DM. The Mungbean(MB) is known as lower Glycemic Index containing food thereby decrease lipid profiles. The purpose of this study is to investigate the inhibitory effects of MB on adipocyte differentiation and insulin sensitivity. The isolated component from MB was treated in dose dependent in 3T3‐L1. Treatment was for 7 days from differentiation induction to fully adipocyte differentiation. Compared to vehicle, lipid accumulation was significantly lower in dose dependent manner. To investigate anti‐obesity, anti‐diabetic effects of MB, MB testa in vivo, we used type2 diabetic model, KK‐Ay mice. MB extract(MBE), MB testa extract(MBT) were orally administrated for 4wks with 60% highfat diet. First of all, AST, ALT were not different compared to the control. Two extract of MBE, MBT significantly lowered IL‐6 levels in plasma but lowered TNF‐a in muscle. Since PPAR¥ã, ACC, C/EBP¥á and AMPK gene expression was decreased by two extracts compared to control and Metformin treated group, MBE, MBT inhibited metabolism of adipogenesis in liver. Most important results was that MBE, MBT reduced epididymal fat weight and reduced those gene expression. In conclusion, MB exerts an anti‐obesity, anti‐diabetic effects. This work is supported by Cooperative Research Program for Agriculture Science&Technology Development(PJ907089)

Grant Funding Source: Agriculture Science&Technology Development, Korea, Republic of
Nutritional status, risky eating behaviors and body dissatisfaction in a population of Mexican artisans
Authors: Parra Alicia , Perez-Lizaur Ana , Masliah Carmen , Velasco Thalia
Published: June 2021

Iberomericana University promotes the exchange of products manufactured by artisans from various ethnic groups in Mexico.

Objective

To evaluate nutritional status, risky eating behaviors and body dissatisfaction in 72 Mexican artisans (27.7% male, 72.2% women, mean age 40.6 years).

Methods

Standardized personal determined % fat and weight (Inbody 720), BMI, capillary glucose (GlucoLab Infopia), and blood pressure ( Genmed aneroid baumanometer ). A brief questionnaire for Risk of Eating Behaviors (CAR), which has been previously validated in Mexican population was applied; to assess body dissatisfaction a discrepancy score was calculated using the actual‐desired body figure using Stunkard figures.

Results

40.27% normal weight, 38.88% overweight, 19.44% obesity and 1.38% underweight, 18.5% hypertension, 54.9% glucose≥ 100 <125 mg / dl, 11.1% diabetes; 48.6% waist circumference at high risk for metabolic syndrome (SSA criteria Mexico). The CAR shows that 12.5% of the participants had moderate risk and 1.3% high risk of eating disorders; 27.7% of participants are satisfied with their body shape, 12.5% want a smaller figure and 59.7% would like a bigger figure.

Conclusion

the population has a high risk for metabolic syndrome and a different body size desire in opposition with occidental body model.
Metabolically healthy overweight/obese premenopausal women benefit from a diet and exercise weight loss intervention
Authors: Durward Carrie M , Shlisky Julie D , Zack Melissa K , Nickols-Richardson Sharon M
Published: June 2021

Body weight (BW) loss is recommended for overweight/obese individuals to lower disease risk, but some clinicians question whether BW loss is necessary for those who are metabolically healthy (MH). In this secondary data analysis from a 6‐mo diet and exercise intervention, women who followed 1 of 2 diet plans showed improved health outcomes regardless of baseline metabolic health status and diet plan. For comparability with previous work showing increased insulin resistance (IR) with BW loss, metabolic health was defined using homeostatic model assessment of IR (HOMA‐IR) quartiles, with ≥2.8 classifying MH (n=19) and ≤1.33 metabolically unhealthy (MU, n=20). Health markers were measured at wks 0, 12, and 24 and repeated measures MANCOVA identified significant changes. Over 12 wks of BW loss, MH and MU, respectively, decreased BW (mean±SD, −5.5±4.1; −7.2±5.0 kg; p≤.001), BMI (−2.0±1.5; −2.5±1.7 kg/m2; p≤.001), waist circumference (−5.3±3.6; −5.9±3.5 cm; p≤.002), body fat % (−3.6±3.3; −3.4±2.6 %; p≤.05), and triglyceride (−15.4±34.6; −34.4±37.9 mg/dL; p≤.05); these changes were maintained for 12 wks of BW loss maintenance. MU also decreased and then maintained HOMA‐IR (−1.7±1.9; p≤.05) and insulin (−7.1±8.9 μIU/mL; p≤.05). A diet and exercise intervention resulting in BW loss can improve health markers in MH and MU women.

Grant Funding Source : The Bell Institute of Health & Nutrition, General Mills Inc
Characterization of swine adipose tissue monocytic lineage cells
Authors: Faris Richard J. , Walker-Daniels Jennifer , Jones Douglas E. , Spurlock Michael E.
Published: June 2021

The incidence of obesity is growing in the United States and other developed countries. Macrophage infiltration into adipose tissue is a key characteristic of human obesity. Swine are increasingly used as biomedical models in obesity research due to physiologic similarities of many systems to those of humans. To examine the similarity of monocytic markers in adipose tissue and to further characterize the pig as a biomedical model with which to study obesity, flow cytometry was performed on stromal vascular cells from adipose tissue biopsies of Yorkshire cross pigs. Adipose tissue stromal vascular cells were 34.2% CD172a+ (monocyte) and 26.9% CD203a+(macrophage). The majority of both CD203a+ and CD172a+ cells were CD163+ (69.8% and 59.0%, respectively) and CD14+ (80.5% and 73.3%, respectively). To determine the effect of mild inflammation on adipose tissue macrophage infiltration, swine were injected intravenously with 50 ng/kg body weight lipopolysaccharide (LPS). LPS injection statistically increased the percentage of both CD203+ and CD172a+ cells in adipose tissue at 24 hours after injection. In conclusion, this study utilizes several cell surface markers to characterize the phenotype of monocytic lineage cells in swine adipose tissue and provides valuable data for future studies examining adipose tissue macrophages in obesity.

Grant Funding Source : Internal Iowa State University
Effect of dietary fat on carbohydrate response element binding protein in a rat model of fatty liver and insulin resistance
Authors: Kuo Yu-Fu , Harper Marianna A. , Clarke Steven , Axen Kenneth , Axen Kathleen
Published: June 2021

The effect of obesity and insulin resistance on content and translocation of carbohydrate response element binding protein (ChREBP) was studied in dietary obese rats.

Method

Male Sprague‐Dawley rats were separated into: LF (N=12) fed 55% carbohydrate: 15% fat (% kcal) and HF (N=8) fed 19% carbohydrate: 55% fat ad libitum for 8 weeks. Liver samples were collected from LF and HF after 20 h food deprivation (D) and then 3 h after oral glucose load (G). Liver protein extracts and homogenates, separated into cytoplasmic and nuclear fractions were analyzed by immunoblotting.

Results

In the deprived state, total ChREBP was greater in HF than LF rats (P<0.05). However, after the glucose load the level of total ChREBP was increased in LF, but not HF rats, resulting in similar levels of total ChREBP in the two groups. In addition, both groups showed similar increases in nuclear ChREBP content after the glucose load.

Conclusion

Higher basal levels of ChREBP protein in the obese group suggest higher basal hepatic fat synthesis than in the lean group. Given that post‐glucose ChREBP protein content and nuclear translocation were similar in both groups, the increase in ChREBP‐stimulated fat synthesis by glucose may be greater in the LF vs. HF group.

Grant number:1 SC3 GM086298‐01A1

Grant Funding Source : SC3GM086298
Insulin sensitization in Female Ob/Ob Mice by an Apo‐ Lipoprotein‐A1 Mimetic are Independent of Effects on Body Weight
Authors: Burgess Angela , Abraham Nader
Published: June 2021

Apo‐lipoprotein‐A1 mimetic, L4F, attenuates insulin resistance, abate metabolic syndrome and reduce cardio‐vascular (CV) morbidity in male obese mice. Hormonal influence on metabolic homeostasis is now well established, as such, we characterized the effects of L4F in female ob/ob vs. male ob/ob mice. Obese (ob/ob) mice were treated with L4F or vehicle daily for 6 wks, I.P. at 2mg/kg/d. Where L4F retarded weight gain in male mice (p<0.05) it had no such effect in female mice. However, L4F did restore insulin tolerance (p<0.05) in female mice and reduced plasma glucose (p<0.05), while enhancing (p<0.05) serum adiponectin levels. Also, L4F treatment in female obese mice reduced circulating levels of inflammatory cytokines (TNFα, IL‐6, IL‐1β, p<0.05) and total cholesterol levels (p<0.05). Metabolic homeostatic markers, such as hepatic p‐AMPK and p‐AKT levels, were enhanced (p<0.05) by L4F treatment. These effects of L4F were accompanied by increased hepatic‐HO1 expression along with increased HO activity with reduced (p<0.05) hepatic expression of GP91‐phox, an indicator of L4Fs attenuative effects on cellular oxidative stress. Taken together, our results show that L4F can restore metabolic homeostasis and reduce systemic inflammation in mammalian females, and because these effects are body weight independent L4F may be used in conjunction with weight loss therapy in obese patients. NIH‐ DK056601
Variability in results from predicted resting energy expenditure (PREE) as compared to measured resting energy expenditure (MREE) in Korean farmers
Authors: Tsani A. Fahmy Arif , Ko Su-Young , Yeon Seo-Eun , Kim Eun-Kyung
Published: June 2021

The purpose of this study was to compare measured resting energy expenditure to results from energy predictive equations to identify the most accurate equation to use for Korean farmers. Subjects were 155 healthy farmers (49 males, 106 females) aged 26–67y. REE (MREE) was measured by indirect calorimetry during the busy farming season. Predicted REE (PREE) was calculated using the 12 equations (Harris‐Benedict, Schofield‐W, Schofield‐WH, WHO‐W, WHO‐WH, Owen, Mifflin, Cunningham, Liu, IMNA, Henry‐W, and Henry‐WH equation). MREE of male farmers was significantly different with of female (1679.2¡¾187.0 vs. 1321.0¡ ¾143.7 kcal/day). The validity of the equations was evaluated on basis of prediction accuracy, difference, RMSPE, % difference, and Bland‐Altman analyses. Measured and predicted energy expenditure were significantly correlated (P< .001 for all), but significantly different for all equations, except Schofield(W&WH), WHO(W&WH), and Henry(WH). The most accurate equation for Korean farmers was the Schofield(W) equation (prediction accuracy 75%, difference −7.4¡¾186.5 kcal/day, RMSPE 137.4 kcal/day, % difference 0.3%). Although PREE were significantly correlated with MREE, the discrepancies from existed equations could produce energy imbalance in Korean farmers, which may influence their productivity.

This research was supported by Korean Rural Development Administration (RDA)
Smaller decreases in protein and greater decreases in fat may be associated with exercise training before body mass reduction
Authors: Nakashima Ayumi , Nishijima Ruri , Okamura Koji
Published: June 2021

The effect of exercise training before body mass reduction on body composition and energy storage in the body after body mass reduction was studied in rats. Twenty‐one rats (all 4 weeks old) were divided into two groups, a sedentary (S, n = 10) or exercise (E, n = 11) group. The rats in the E group performed climbing exercise training for 3 weeks. The protein, total lipid and glycogen levels in homogenized carcasses were measured both before and after a 3 day fast (n = 5 – 6). The body mass, a sum of the masses of the excised skeletal muscles and adipose tissues did not differ between the groups before and after the 3 day fast. The difference in the mean body mass before and after the 3 day fast was similar in the S and E groups (S −54.1 vs. E −53.7 g). The difference in the mean protein level was greater in the S than the E group (S −20.1 vs. E −15.6 kcal), while the difference in total lipids was lower in the S than the E group (S −82.7 vs. E −116.3 kcal). Glycogen decreased comparably between the groups (S −0.5 vs. E −0.6 kcal). As a result, the decrease in the energy stored in the body after the 3 day fast was lower by 22% in the S group than in the E group (S −103.3 vs. E −132.5 kcal). Exercise training before body mass reduction may therefore be associated with a smaller decrease in lean body tissues and a greater decrease in adipose tissues.