bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Diet‐induced Obesity on Protein Expressions of Insulin Signalling Pathways in the Skeletal Muscle of Male Wistar Rats
Authors: Fatani Sameer , Itua Imose , Naderali Ebrahim 
Published: June 2021

Effects of Diet‐induced Obesity on Protein Expressions of Insulin Signalling Pathways in the Skeletal Muscle of male Wistar RatsThe exact mechanism involved in insulin transduction in skeletal muscle is not well understood. Protein expressions of PI 3‐kinase and MAP‐kinase insulin signalling pathways in skeletal muscle of diet induced obese rats were investigated.Male Wistar rats (190 ± 3g) were randomly allocated to control, vehicle (diet induced obese animals), diet‐to‐chow and fenofibrate treated group. Expression of proteins involved in insulin signalling was determined by western blotting. Triglyceride (TG) content of skeletal muscle was determined by homogenising 160–200mg gastrocnemius muscle in 500μl distilled water and assaying the supernatants. Results were normalised and compared to control using student t test or repeated measures one‐way ANOVA or Mann‐Whitney test. Data are expressed as mean ± SEM and considered significant at p<0.05.Vehicle animals were significantly heavier than control, diet‐to‐chow and fenofibrate animals. TG levels in vehicle were significantly increased compared to other groups. IR‐β and IRS‐1 were unaffected. PKC‐β, regulatory subunit p85 of PI 3‐kinase and eNOS respectively were significantly increased in vehicle and fenofibrate groups. Akt in diet‐to‐chow were significantly lower than vehicle group. Shc and ERK1/2 were significantly increased in vehicle.Thus in diet induced obesity, insulin resistance in skeletal muscle is achieved by increasing expression of p85 of PI 3‐kinase.
Upregulation in the Expression of Tryptophan Hydroxylase 2 (TPH2) in the Lower Brainstem in Depression
Authors: Kerman Ilan A , Amilineni Nina , Jones Edward G. , Bunney William E. , Huda Akil , Watson Stanley J. 
Published: June 2021

In addition to affective disturbances depression is characterized by physical symptoms, which suggest dysfunction of motor, autonomic, and pain regulatory systems. These functions are modulated by serotonin (5‐HT), and extensive evidence implicates dysfunction in its neurotransmission in the pathophysiology of depression. In the current study we examined gene expression of TPH2, a key enzyme in 5‐HT synthesis, within brainstem regions that contain spinally‐projecting 5‐HTergic neurons. We collected post‐mortem human brainstem samples from depressed and control subjects, and used a combined neurochemical and histological staining approach to identify 5‐HT cell groups in the lower brainstem that are homologous with those in other species. Using radioactive in situ hybridization we detected an upregulation in TPH2 expression within: raphe obscurus, gigantocellular nucleus pars α, and raphe magnus. These regions are well‐known to regulate somatomotor, sympathetic, and nociceptive functions, and a similar increase in TPH2 expression has been reported within ascending 5‐HTergic cell groups. Taken together, these findings suggest shared molecular alterations within distinct 5‐HT circuits that mediate affective and physical manifestations of depression.Support: Pritzker Neuropsychiatric Disorders Research Consortium, 5K99MH081927‐02 (to IAK), and NARSAD Young Investigator Award (to IAK).
The Effects of Hindlimb Suspension on Proteins Essential to Cholesterol Metabolism in Rat Skeletal Muscle
Authors: Lee Teak Veng , Swift Joshua M , Chen Vincent CW , Lee Chang Woock , Bui Steve , Riechman Steven E 
Published: June 2021

IntroductionHindlimb suspension (HS) results in significant deleterious effects on numerous physiological systems, including atrophy of weight‐bearing muscles. However, HS and its effects on proteins essential for cholesterol metabolism have not been investigated in unloaded skeletal muscle. Cholesterol serves as a critical constituent of all cell membranes, including skeletal muscle. The purpose of this study was to examine the effects of 28 days of HS on sterol regulatory element‐binding protein 2 (SREBP‐2), which is a transcriptional factor necessary for endogenous cholesterol synthesis. We hypothesized that HS causes a downregulation of this protein in rat skeletal muscle.MethodsTwelve male Sprague‐Dawley rats, 6 months of age, were hindlimb suspended for 28 days (HS; n=5) or served as cage controls (CC; n=7). After 4 weeks, plantarflexor muscles were harvested, weighed and analyzed by Western Blotting for SREBP‐2.ResultsSoleus muscle mass and soleus muscle mass to body mass were significantly different between groups (HS: 97.0 ± 14.2 mg and 0. 22 ± 0. 03 mg/g; CC: 244.3 ± 38.1 mg and 0.49 ± 0. 06 mg/g, P < 0.05). However, mature SREBP‐2 was not significantly different between groups (HS: 0.66 ± 0.31 arbitrary units (AU) and CC: 1.06 ± 0.39 AU, P=0.09).ConclusionAfter 28 days, HS resulted in significant decreases in soleus muscle mass, but not mature SREBP‐2, as compared to cage controls.
Connecting tubule glomerular feedback (CTGF) antagonizes tubuloglomerular feedback (TGF) in vivo
Authors: Wang Hong , Garvin Jeffrey L. , Carretero Oscar A. 
Published: June 2021

We recently described that there is crosstalk between the connecting tubule (CNT) and the Af‐Art that causes dilation. CTGF is mediated by CNT Na transport via epithelial Na channels (ENaC). We hypothesized that CTGF opposes TGF. We performed renal micropuncture studies in male rats. We induced TGF by increasing late proximal perfusion rate (0, 10, 20, 40, 80 nL/min). Stop‐flow pressure (PSF) was used as an index of TGF response. First, we showed that TGF was reversible and reproducible. Next, we tested whether inhibition of CTGF with benzamil (ENaC inhibitor; 1 μM) potentiated TGF. In control, high flow (80 nL/min) increased PSF indicating that CTGF increased Af‐Art dilatation. CTGF inhibition with benzamil potentiated the TGF response, especially at high flow rates. When NaCl transport in the distal tubule was inhibited with hydrochlorothiazide (HCTZ, 1 mM) to increase delivery of Na to the CNT, benzamil potentiated the TGF response at lower (20 nL/min) flow rates (Table). We conclude that CTGF antagonizes the vasoconstrictor effect of TGF.

Perfusion rate (nL/min)
0
10
20
40
80

Control PSF (n=5)
39.6 ± 0.8
39.2 ± 0.6
36.4 ± 0.8
32.4 ± 0.9
34.2 ± 0.8†

Benzamil PSF
39.1 ± 0.8
38.7 ± 0.7
35.7 ± 0.9
30.1 ± 0.8**
30.1 ± 0.7***

HCTZ PSF (n=4)
40.0 ± 0.6
40.3 ± 0.6
37.4 ± 0.5
33.5 ± 0.8
35.5 ± 0.8†

HCTZ+Benzamil PSF
39.8 ± 0.4
39.9 ± 0.5
35.8 ± 0.4#
31.0 ± 0.6#
30.9 ± 0.6#

p < 0.01 and
p < 0.001 vs. control;
p < 0.05 vs. HCTZ;
p < 0.001 40 vs. 80 nL/min

Source of Funding: This study was supported by NIH Grants HL028982 and HL088036.
Hyperglycemia induces apoptotic signaling in first trimester cytotrophoblast cells (1010.6)
Authors: Leonard Dean , Horvat Darijana , Beeram Madhava , Allen Steven , Meininger Cynthia , Zawieja David , Kuehl Thomas , Uddin Mohammad 
Published: June 2021

Objective: Diabetes mellitus is a risk factor for preeclampsia (preE). The mechanism contributing to this effect is not well known. It is evident that dysfunction of cytotrophoblast cells (CTBs) plays a role in the pathogenesis of preE. We have reported that hyperglycemia downregulates factors for invasion and induces an anti‐angiogenic milieu in CTBs. This study assessed the apoptotic signaling in hyperglycemia‐induced CTBs dysfunction. Methods: Human CTBs were treated with 100, 150, 200, 300 or 400 mg/dL glucose for 48h. Some cells were pretreated with p38 inhibitor (SB203580) or peroxisome proliferator‐activated receptor gamma (PPARγ) ligand (rosiglitazone). Thereafter, cell lysates were utilized to measure Bax, Bcl2, Cox‐2 and PPARγ expression and p38 MAPK phosphorylation by western blot. Comparisons were performed using ANOVA with Duncan’s post hoc test. Results: The expression of Bax (2.5 fold), Bcl2 (1.8 fold), Cox‐2 (2.1 fold) and PPARγ (1.8 fold) and p38 MAPK phosphorylation (1.7 fold) were up‐regulated (p<0.05) in CTBs treated with 蠅150 mg/dL glucose compared to basal (100 mg/dL). SB203580 or rosiglitazone pretreatment attenuated glucose‐induced stress and apoptotic signaling. Conclusions: Exposure of CTBs to hyperglycemia induces apoptotic signaling. Attenuation of this signaling by SB203580 or rosiglitazone pretreatment suggests involvement of p38 and PPARγ in this signaling cascade.Grant Funding Source: N/A
IP7K is kinetically well‐equipped for cell signaling but does not regulate CDK5 activity (1013.12)
Authors: Weaver Jeremy , Shears Stephen 
Published: June 2021

Inositol pyrophosphates (PP‐InsPs) such as 1‐IP7 and IP8 serve as cellular signals that interface nutrient status with cellular growth and energy homeostasis; PP‐InsP turnover may impact bioenergetic diseases such as diabetes and cancer. In yeast, 1‐IP7 regulates phosphate response genes through its inhibition of the Pho85 cyclin‐kinase complex. Yet the relationship between cellular energy status and PP‐InsP synthesis is unclear. We characterized the ATP‐dependent kinase activity of human IP7K2. The IP7K2 Vmax (190 +/‐ 10 nmol/mg/min) is comparable to that of IP6K. Unlike IP6K, IP7K2 is not reversible in a physiologically‐relevant bioenergetic environment (i.e. [ATP]>[ADP]); the equilibrium point favors 80‐90% 1‐IP7 and IP8 accumulation. Furthermore, IP7K2 was insensitive to physiologically‐relevant changes to either [AMP], [ADP] or to [ATP] itself (since the ATP Km = 20‐40 µM). We further showed that regulation of yeast cyclin‐kinase by 1‐IP7 is not conserved for the homologous mammalian CDK5 complex. To interrogate potential signaling roles of IP7K2, we demonstrate in L6 skeletal myoblasts that either insulin, IGF or PDGF can each raise IP8 levels 2‐3 fold. Thus, we show independent of the bioenergetic context, IP7K2 is kinetically well‐equipped to participate in rapid cell‐signaling events and that cells place PP‐InsP synthesis under receptor regulation. Precedents suggest this is a valuable observation: demonstrations of receptor‐regulation of levels of IP3 ‐ and, later, PIP3 ‐ were critical in fermenting widespread interest in these molecules as cell‐signals.Grant Funding Source: This work was supported by the NIEHS.
Potential of glycated proteins produced during aging of cheddar cheese to modulate fecal bacteria from obese mice ex vivo and protect against colon inflammation (1018.5)
Authors: Yuan Jialing , Noratto Katherine , Munske Gerhard , Pilla Paulina , Mohanty Indira , Alcantara Zapata Diana , Noratto Giuliana 
Published: June 2021

Cheddar cheese aging promotes the production of glycated proteins with potential to improve intestinal health.We investigated major changes on proteins of aged cheddar cheese (Cougar Gold) during ripening up to 24 months using HPLC/MS‐MS. The proteins effects on fecal bacteria from obese mice after in vitro intestinal digestion, and the effects of metabolites produced during fecal fermentation were evaluated. We further assessed the effects of metabolites from fecal fermentation on production of reactive oxygen species (ROS) in colon epithelial HT‐29 and the fibroblast CCD‐18Co cells challenged with E. Coli lipopolysaccharides (LPS) following standard analytical procedures.Results demonstrated that cheese aging (6‐24 months) produced soluble glycosylated proteins of MW ~ 23 kDa mainly derived from α‐S1‐ and β‐casein. Cheese glycated proteins were resistant to in vitro gastrointestinal digestion and changed the relative abundances of fecal bacteria by increasing Bacteroidetes/Firmicutes ratio and Bifidobacterium compared to the casein fermented controls. These changes resembled relative abundances of bacteria in feces from lean mice control. Furthermore, metabolites produced during fecal fermentation protected both the HT‐29 and CCD‐18Co cells from LPS‐induced ROS. We are currently investigating the molecular targets of glycated proteins and metabolites produced after fecal fermentation that protect colon cells from inflammation. These results are relevant for gut health.
Comparison of corresponding commercially processed foods from store and restaurant for sodium, fat, sugar and potassium content in a nationwide sample (1019.11)
Authors: Ahuja Jaspreet , Pehrsson Pamela , Haytowitz David , Showell Bethany , Nickle Melissa , Wasswa‐Kintu Shirley , Cogswell Mary 
Published: June 2021

Data comparing the nutrient content of commercially processed food items from restaurant and store are limited. Eleven highly consumed food items were sampled nationwide from the two sources ‐ restaurant and store (e.g., chicken nuggets, frozen and fast food), under the USDA’s National Food and Nutrient Analysis Program. Nutrient data are now available for 4 pairs. Two sample T‐tests and Mann‐Whitney U‐tests were used to compare corresponding foods. Store chicken nuggets were lower in sodium and total fat than fast food restaurants (559±98.8 vs. 594±241 mg/100 g, p=0.028 and 16.2±3.2 vs. 20.4±4.9 g/100 g, p=<0.0001, respectively), as were store thin crust cheese pizzas (471±45 vs. 742±349.9 mg/100 g, p<0.0001 and 11.1±1.3 vs. 14±4 g/100 g, p=<0.0001, respectively). Store chili with meat and beans were higher in sodium (449±21.7 vs. 381±38.3 mg/100 g, p=0.0003), but about a third lower in total fat and saturated fat than those obtained from restaurant. Store macaroni and cheeses were higher in sodium and potassium than restaurant (682±74.1 vs. 361±83.4 mg/100 g, p<0.0001 and 355±26.3 vs. 135±35.2 mg/100g, p<0.0001). These results do not indicate any consistent differences between the two sources. These studies will help our understanding of the food environment, strengthen national nutrition monitoring, and update the USDA National Nutrient Database for Standard Reference (SR), the most authoritative food composition database in the US.Grant Funding Source: Funding Source: CDC‐USDA Agreement 60‐1235‐0‐185
Influence of editing free text responses on nutrient and food group estimates from the Automated Self‐Administered 24‐hour dietary recall (ASA24) (1022.7)
Authors: Potischman Nancy , Zimmerman Thea , Douglass Deirdre , Dixit‐Joshi Sujata , Kirkpatrick Sharon , Subar Amy , McNutt Suzanne , Coleman Laura , Alexander Gwen , Kushi Lawrence , Thompson Frances 
Published: June 2021

OBJECTIVE: To assess the impact of editing data from the ASA24 on nutrient and food group estimates.METHODS: About 900 adults from 3 integrated health care systems completed recalls in an ASA24 evaluation study. In using ASA24, respondents may enter free text in 2 contexts. “Other” is a response to questions about food detail (e.g., brand name), in which case text is collected but not used in assigning food codes. Text can be entered for “Unfound foods” when respondents cannot find a food. The system asks questions to identify the food type and assigns a food code. Free‐text responses were compared to system‐assigned food codes and edited when necessary. Nutrient and food group values for unedited and edited data were then compared.RESULTS: Of 1,013 recalls collected, 440 recalls included 749 foods with free text responses. The ASA24 system assigned correct food codes 70% of the time. Edits were made to 225 foods (30% of foods reported using free text), affecting 188 recalls (18.5% of all recalls). This editing process required over 60 hours of specialized staff time. The mean nutrient and food group values before and after editing showed no significant differences.DISCUSSION: These results allow researchers using ASA24 to weigh the benefits and costs of manually reviewing free text responses.
The impact of dairy consumption on circulating cholesterol levels is modulated by common single nucleotide polymorphisms in cholesterol synthesis‐ and transport‐related genes (1038.4)
Authors: Abdullah Mohammad , Cyr Audrey , Labonté Marie‐Ève , Lépine Marie‐Claude , Couture Patrick , Eck Peter , Lamarche Benoît , Jones Peter 
Published: June 2021

Dairy consumption impacts circulating cholesterol levels, a traditional risk marker for cardiovascular health, however, whether genetics play a role in response to dairy has not been established. Our objective was to evaluate 24 candidate SNPs within 13 cholesterol synthesis‐ and transport‐associated genes in relation to the cholesterol metabolism response to an intake of conventional and commonly‐consumed dairy products in Canada. Normolipidemic adults (n=101) consumed 3 servings/d of dairy (1% fat milk, 1.5% fat yogurt, and 34% fat cheese) or energy‐matched control products for 28 d using a multicentre, randomized, free‐living, crossover design. Relative to the control diet, dairy intake was associated with an increase in plasma levels of total cholesterol (TC) and LDL‐C only in carriers of the cholesterol transport gene ABCG5 SNP rs6720173‐G/G (4.86±0.20 vs. 5.05±0.20 mmol/L, n=72, p=0.008) and (2.86±0.14 vs. 3.03±0.14 mmol/L, p=0.002), cholesterol synthesis gene SREBF2 SNP rs2228314‐G/G (4.98±0.16 vs. 5.21±0.16 mmol/L, n=50, p=0.02) and (3.06±0.15 vs. 3.24±0.15 mmol/L, p=0.03), and bile acid synthesis gene CYP7A1 SNP rs3808607‐G/T (5.00±0.16 vs. 5.21±0.16 mmol/L, n=53, p=0.04) and (2.93±0.14 vs. 3.11±0.14 mmol/L, p=0.01) genotypes, respectively. These findings accordingly suggest the existence of a gene‐diet interaction modulating the impact of dairy intake on circulating cholesterol levels.Grant Funding Source: Supported by Dairy Farmers of Canada (DFC) and Agriculture and Agri‐Food Canada (AAFC)
A new biomarker for quinoa intake (1044.25)
Authors: Ross Alastair , Savolainen Otto 
Published: June 2021

Quinoa (Chenopodium quinoa) is a pseudocereal grain consumed widely in the Andean regions of South America, and now receiving greater attention in many countries as a gluten‐free grain with a balanced amino acid profile. To date there has been little work on quinoa composition, clinical effects, or association of quinoa intake with health outcomes. We identified a range of alkylresorcinols in quinoa using LC‐MS/MS and GC‐MS/MS, including odd numbered homologues C17:0 ‐ C25:0 identified in whole grain wheat, rye and barley. In addition, we have identified homologues C18:0, C22:0, and C24:0, to our knowledge the first time these have been reported in nature. As these even numbered homologues may be unique to quinoa they may serve as a biomarker of quinoa intake. To test this hypothesis, we measured alkylresorcinols in plasma before and after intake of quinoa and were able to measure alkylresorcinol homologues in plasma.Alkylresorcinols, in food previously only thought to be present in wheat, rye and barley, are also present in quinoa, and unique alkylresorcinol homologues may serve as specific biomarkers of this pseudocereal.
Biomarkers for Western diet accentuated cellular damage in benzo(a)pyrene‐induced colon cancer (1052.2)
Authors: Harris Kelly , Pulliam Stephanie , Niaz Mohammad , Okoro Emmanuel , Guo Zhongmao , Washington Mary , Adunyah Samuel , Ramesh Aramandla 
Published: June 2021

The role of fat content in diet has been linked to the development of several types of cancers. We have investigated the effect of dietary fat type on benzo(a)pyrene (an environmental toxicant)‐induced colon cancer in an adult male rat model, the Polyposis In the Rat Colon (PIRC) kindred type. Groups of PIRC rats (n = 5) were fed with AIN‐76A regular diet (RD) or Western diet (WD) and these rats also received 25,50 and 100 µg B(a)P/kg body wt., daily via oral gavage for a period of 60 days. At the end of exposure period, rats were sacrificed; blood samples were collected and concentrations of cholesterol, triglycerides, glucose, insulin, adiponectin, reactive oxygen species (ROS) and oxidative damage to DNA were measured. Colon tissues were scored for tumors, and preserved in 10% formalin for observation of pathological changes. Rats that received WD + B(a)P registered increased levels of cholesterol,triglycerides and insulin in comparison to rats that received RD + B(a)P and also controls. Levels of glucose stayed the same between WD and RD for 25, and 50 µg B(a)P/kg body wt., but showed a significant difference (p < 0.001) at 100 µg B(a)P/kg body wt. with WD group showing high concentrations. The concentrations of adiponectin did not vary much between WD and RD groups for all the B(a)P doses used. Maximal levels of ROS and oxidative DNA damage in blood were noticed in WD + B(a)P rats compared to RD + B(a)P rats and controls. Additionally, the DNA damage was found to be B(a)P dose‐dependent. The colon tumor counts were more in B(a)P + WD rats compared to their B(a)P + RD counterparts, and also exhibited a B(a)P dose‐response relationship, with 100 µg B(a)P/kg registering greater counts. Adenomas with high grade dysplasia were prominent in B(a)P + WD rats compared to B(a)P + RD rats. Taken together, our findings revealed that WD potentiates the development of colon tumors induced by B(a)P through proinflammatory action, characterized by an increased generation of ROS and oxidative damage.Grant Funding Source: Supported by 5RO1CA142845‐04,5T32HL007735‐19,5R25GM059994‐11,Southern Regional Education Board
Methyl salicylate lactoside inhibits inflammatory response on fibroblast‐like synoviocytes and collagen‐induced arthritis by inhibiting NF‐κB activation (1056.2)
Authors: Zhang Tiantai , Xin Wenyu , Huang Chao , Du Guanhua 
Published: June 2021

Methyl salicylate 2‐O‐β‐D‐lactoside (MSL), whose chemical structure is correlated with salicylic acid, is a natural product derivative isolated from a traditional Chinese herb. The aim is to investigate the therapeutic effect of MSL in collagen‐induced arthritis (CIA) mouse and explore its underlying mechanism. DBA/1 mice CIA model was adopted to evaluate the anti‐arthritis effect of MSL. Fibroblast‐like synoviocytes (FLS) from RA patients were stimulated by TNF‐α to determine the production of proinflammatory cytokines, immunofluorescence staining, and proteins expression.The results showed that MSL significantly prevented the progression of arthritis in CIA mice without gastric mucosa toxicity. Administration of MSL inhibited the production of TNF‐α and IL‐1β, and the phosphorylation of IKKβ, IκBα, and p65 in joint tissue of CIA mice. MSL also suppressed the IL‐1β and IL‐6 production, and release of NO and PGE2 in TNF‐α‐induced FLS. Accordingly, the expression of iNOS, COX‐1, and COX‐2 were also reduced by MSL. We further demonstrated that MSL inhibited the phosphorylation of IKKβ, IκBα, and p65, blocked the nuclear translocation of NF‐κB in TNF‐α‐induced FLS. MSL inhibits the development of arthritis in CIA mice and without gastric mucosa toxicity. The underlying mechanism may be related to suppress the NF‐κB activation, and non‐selective inhibit the COX. Therefore, MSL has great potential to be a novel natural product agent for prevention and/or treatment of RA.