bluuebunny/crossref_metadata_2025 huggingface dataset:
Occludin Deficiency Exacerbates Ethanol‐Induced Colonic Barrier Dysfunction and Liver Damage
Authors: Mir Hina R. , Gangwar Ruchika , Chaudhry Kamaljit K , Manda Bhargavi , Shen Le , Turner Jerrold R , Dietrich Paula , Dragatsis Ioannis , Rao RadhaKrishna
Published: June 2021

Epithelial tight junctions (TJs) confer barrier function in the intestinal mucosa. Occludin is one of the transmembrane proteins of TJs. Occludin knockout (OKO) mice showed no apparent anomaly in the intestinal epithelial TJs. Hence, the function of occludin is undetermined. Recent studies indicated the potential role of occludin in apoptosis and cell migration. Chronic ethanol feeding (CEF) increases colonic permeability and causes liver damage. We evaluated the susceptibility of OKO mice to CEF‐induced gut barrier dysfunction and liver damage. Wild type (WT) and OKO mice were fed a liquid diet containing ethanol (1% 2d, 2% 2d, 4% 1wk, 5% 1wk and 6% 1wk). Control mice were pair fed (PF) with isocaloric maltodextrin. CEF led to a significant loss of body weight in OKO mice, compared to WT mice. Colonic mucosal permeability in vivo, measured as plasma to lumen flux of FITC‐inulin, was ~3 fold greater in EF‐OKO mice. CEF induced redistribution of ZO‐1 from the intercellular junctions; redistribution was more severe in EF‐OKO mice. CEF increased liver weight and plasma ALT activity in OKO mice, but not in WT mice. H&E, Oil red‐O and Sirius red staining showed that CEF induced greater levels of fat deposition, focal lesions and collagen accumulation in liver of EF‐OKO mice than in WT mice. In summary, results indicate that occludin deficiency increases susceptibility to CEF‐induced colonic barrier disruption and liver damage.
Epidermal growth factor modulates colon epithelial innate immune signaling
Authors: Dubé Philip , Polk D. Brent
Published: June 2021

Epidermal growth factor (EGF) and its receptor (EGFR) enhance colon epithelial healing through cell migration, proliferation and survival. Since barrier disruption induces epithelial innate immune activation by luminal microbial products, such as lipopolysaccharide (LPS) acting through toll‐like receptor 4 (TLR4), we sought to determine if EGF modulates this response as an additional mechanism to limit inflammatory responses and optimize healing. We hypothesized that EGF inhibits epithelial responses to TLR activation.

Methods

Mouse colon epithelial cells (YAMC) were used to determine the effect of EGF on TLR expression (qRT‐PCR) and function (NFκB luciferase reporter, CXCL2 mRNA induction, and chemokine secretion by ELISA or multiplex bead array)

Results

EGF suppressed TLR4 and 7 mRNA in a sustained manner without affecting other TLRs. This was specific to epithelial EGFR, and was not observed in macrophages, or in response to other growth factors or cytokines. EGF treatment inhibited colon epithelial NFκB activity in response to LPS and triacylated lipopeptide (TLR1/2 agonist). EGF also reduced LPS‐induced CXCL2 mRNA and secretion of CXCL2, GCSF, LIF, IL‐6 and GM‐CSF. The EGF inhibition of LPS‐induced NFκB activity required the adaptor protein YMER and was abolished by YMER siRNA.

Discussion

These results uncover a novel role for EGF to modulate TLR signaling in colon epithelial cells at the level of expression and function. These effects appeared specific to epithelial cells and required a cytosolic EGFR substrate, YMER. Thus, EGFR modulates epithelial responses to microbial cues and may provide an immunomodulatory signal for the colon epithelium. Since TLR4 transactivates EGFR, this may be a feedback mechanism whereby EGFR activation limits TLR responses. Support by NIH and CCFA.
Hemorrhagic shock induces predominant damage to the proximal small intestine in the mouse
Authors: Richards Jennifer Lynn , Phillips Neil , King Michelle , Clanton Thomas
Published: June 2021

A variety of stress‐states cause intestinal mucosal damage. Hemorrhagic shock (HS) is known to do so via reductions in intestinal blood flow, resulting in ischemia. This study had two objectives: first, we evaluated whether an acute hemorrhagic shock model in the mouse induced intestinal damage; second, we determined if there existed regional susceptibilities to injury as those we previously identified in another stress condition, hyperthermia. In lightly anesthetized C57BL/6 mice, 30% of their blood volume was removed by transthoracic intracardiac puncture. Withdrawn blood was kept at 37°C for 60 min and re‐injected through the retro‐orbital sinus under anesthesia. The animals recovered for another 60 min, were then re‐anesthetized, a second blood draw performed and intestines harvested and fixed for later histological evaluation. Significant histological damage was observed in the duodenal (DU) intestine in HS vs. sham control (P < 0.02), with no significant damage seen in the jejunum (JE) or Ilium (IL). The DU in HS animals also exhibited significant reductions in villus height and total mucosal thickness (P < 0.003, P< 0.003 respectively). There were no effects of HS on average villus width or crypt depth. Results demonstrate that in acute HS in the mouse, regions of the intestine near the stomach are most vulnerable to damage within one hour, post HS. The pronounced shortening of the villi observed at this time likely reflects ongoing intestinal repair strategies that are used to remove damaged epithelium. AHA #11GRNT7990119
Probiotic use decreases intestinal inflammation and increases bone density in healthy male but not female mice
Authors: McCabe Laura R , Irwin Regina , Schaefer Laura , Zhang Jing , Quach Darin , Britton Rob
Published: June 2021

Intestinal inflammation (ie: inflammatory bowel disease, IBD) can cause osteoporosis. Probiotics, beneficial microorganisms, are currently being examined to reduce gut inflammation and treat IBD. Here, we tested if treating healthy male and female mice (moved from pathogen free to standard housing) with L. reuteri (a probiotic with anti‐TNF activity) could affect intestinal and bone health. Adult mice were given L. reuteri orally by gavage 3X/week for four weeks. L. reuteri suppressed basal intestinal TNF mRNA levels in male mice, but interestingly not female mice. Microcomputed tomography identified that L. reuteri intake increased trabecular bone parameters (mineral density, volume, trabecular number, etc..) in the distal femur metaphyseal region as well as in the lumbar vertebrae in male mice. In contrast, female mice did not display a bone response. Cortical bone parameters did not change in either gender. Histomorphometry and serum makers indicate increased osteoblast bone formation in L. reuteri treated male mice. Taken together our studies indicate that responses to oral probiotic use are gender dependent; only males display increased osteoblast activity and enhanced bone volume.
Maternally derived mitochondria in SHR exhibit significant reduction in oxidative phosphorylation gene expression
Authors: Collett Jason A , Paulose Jiffin K. , Cassone Vincent M. , Osborn Jeffrey L.
Published: June 2021

Mitochondrial (Mt) dysfunction contributes to the pathophysiology of renal function and promotes cardiovascular disease including hypertension. We hypothesize that renal Mt‐genes derived from female SHR are linked to high blood pressure in offspring of SHR and normotensive (NT) Brown Norway (BN) rat crosses. After breeding a female Okamoto‐Aoki SHR (MAP=160mmHg) with a BN male (MAP=91mmHg), hypertensive female progeny were backcrossed with the founder BN for 5 consecutive generations. Mt‐protein coding genes (13 total) and nuclear transcription factors mediating Mt‐transcription were evaluated in kidney, heart and liver of NT(n=20) vs. HT(n=20) SHR/BN using quantitative real‐time PCR. GAPDH was used as reference. Renal but not liver or heart Mt‐gene expression was decreased ~2–5 fold in 12 of 13 protein coding genes of HT SHR/BN. Renal but not liver mRNA expression of nuclear transcription factors for Tfam, NRF1, NRF2 and Pgc1α were decreased in HT SHR/BN. This renal specific reduction of nuclear and Mt‐gene expression may down‐regulate oxidative metabolism and increase renal reactive oxygen species production in SHR leading to hypertension and cardiovascular disease.
Selection of candidate genes for hypertension on rat chromosome 4 from shr using expression profilling in kidney and subcongenic strain development
Authors: Teixeira Samantha Kuwada , Rodrigues Mariliza Velho , Morales Marcelo Marcos , Krieger José Eduardo
Published: June 2021

Using total genome scan, we previously mapped 5 BP‐related QTLs that explain 38% of the BP variance in a progeny derived from Spontaneous Hypertensive Rat (SHR) and Brown Norway (BN) rats. The QTLs were then validated by derivation of congenic strains, including one for chromosome 4 (SHR.BN4) in which a segment from BN replaced the SHR sequences reducing basal systolic BP (~15 mmHg). To select the putative candidate genes, we used genomic approaches based on differential expression in kidney samples and development of subcongenic strains. Sixteen genes were differentially expressed in samples from adult renal tissues from congenic strain SHR.BN4 compared with SHR. Of those, seven remained differentially expressed in the kidney from pre‐hypertensive animals displaying comparable levels of blood pressure. We then verified which of those candidate genes were expressed along the nephron and if they were differentially expressed in mRNA samples from 5 microdissected nephron segments from the two groups. All 7 genes were differentially expressed in one or more of the nephron segments between the 2 strains. Meanwhile, two nonoverlapping congenic substrains were obtained from SHR.BN4, which maintained its phenotype, and one of those harbours 2 of the candidate genes (MGC95152 and Aqp1). Taken together, the combined approaches resulted in selection of 2 hypertensive candidate genes that deserve to be further explored.

Supported by FAPESP, CNPq and E.J. Zerbini
AN OVERVIEW OF STUDY METHODOLOGY AND KNOWLEDGE RETENTION IN VETERINARY ANATOMY ON DVM STUDENTS
Authors: Trincado Carlos , Gutierrez J. Claudio , Freeman Larry
Published: June 2021

Anatomy is considered a cornerstone in medical education. Dissecting anatomical pieces, is the ideal way to learn this subject. However, always there is a limitation, since the access to the anatomy lab and the number of cadavers is restricted. That is why throughout the history of anatomy instructions, other academic tools have emerged such as photographic atlas, new preservation techniques such as plastination, and more recently, the use of computer software technology.

The aims of this study were to collect information on the supportive methods used by freshmen DVM students and the quality of knowledge retention in senior students that coursed the Bovine Anatomy class in the Veterinary Sciences College of the Austral University of Chile. The implementation of a survey and a diagnostic exam were used for this purpose.

Results showed that the main material used by freshmen students to support their preparation for the Anatomy exams books (38.5%), and that only 12.2 % of the students used some computer technology. Results might be explained by the absence of a complete Anatomy software for the bovine species. Therefore, almost all students (97.8%) agreed with the possibility of having a computer software for complementing the study of Bovine Anatomy. Regarding the diagnostic exam there were only 33.2% of correct answers which represent a low retention of knowledge in senior DVM students.
An in vitro and in vivo study of antitumor effects of naringenin on gastric cancer model.
Authors: Dhanapal Sakthisekaran , Ganapathy Ekambaram
Published: June 2021

The purpose of this study was to investigate the effect of naringenin, a bioflavonoid found in citrus fruits, on the inhibitory effect on AGS cell line and antitumor effect on N‐methyl‐N‐nitro‐ N‐nitrosoguanidine (MNNG)‐induced gastric carcinogenesis. The animals were divided into five groups with six animals in each group. Group I as control (corn oil, 1ml/rat) and group II received MNNG (200 mg/kg body weight, by oral gavage) and S‐NaCl (1ml/rat) for the induction of cancer. Rats in group III were treated with naringenin (dissolved in corn oil, orally 200 mg/kg b.wt,) simultaneously after animals received a first dose of MNNG (as in group II). Group IV were given naringenin from the 6th week of MNNG administration for up to 20 weeks post treatment. Group V rats were given naringenin alone. Administration of naringenin significantly decreased the levels of Reactive oxygen species, lipid peroxidation, protein carbonyls, nucleic acid contents and polyamine synthesis in gastric carcinogenesis‐induced animals. Additionally, we observed minimal DNA fragmentation and oxidative stress‐induced DNA damage as measured by single cell gel electrophoresis (comet assay) in naringenin treated gastric carcinoma‐induced animals. We hypothesize that free radical scavengers could inhibit MNNG‐induced DNA damage in addition to upholding the antitumor potentials of naringenin in cancerous tissues.
Quantification of Endogenous Matrix Metalloprotease 8 (MMP‐8) in Dentinal Cavity Walls
Authors: Buis William Peter , Kang Justin T , Cho Ellen , Blatz Markus B , Ozer Fusun , D'Angelo Marina
Published: June 2021

Inhibition of matrix metalloproteinase (MMP) activity is expected to increase the long‐term stability and durability of resin‐based restorations by preventing degradation of denuded collagen fibrils in the hybrid layer. Endogenous MMP‐8, released by adhesive procedures, can hydrolyse collagen fibrils at resin/dentin interfaces compromising adhesive bond durability. In this study, occlusal surfaces of n=4 extracted non‐carious human molar teeth (<2 days from extraction, stored −80°C) were removed using a low‐speed diamond saw. 2×4×2mm cavity was prepared on the dentinal surface, leaving surrounding dentinal walls of 1mm thickness. Cavity walls were then acid‐etched with 38% phosphoric acid, pulverized using a liquid nitrogen analytic mill, demineralized in 1% phosphoric acid, suspended in extraction buffer (100mM Tris‐HCl pH 7.6, 0.1mM ZnCl2, 100mM CaCl2, 200mM NaCl, 1% Triton X‐100) and centrifugally concentrated. The results of our study showed that an average of 0.238pg MMP‐8/mg dentin is present as measured by ELISA. This study is the first of its kind to identify endogenous levels of MMP‐8 present in a single‐tooth dentin sample. This information will contribute to the design of specific, clinical inhibition of endogenous MMP activity in dentinal cavity walls to prolong the longevity of resin‐based restorations.
Differential effects of diet composition and exercise on human hunger and satiation
Authors: Lin Po‐Ju , Borer Katarina
Published: June 2021

How diet composition and exercise influence human hunger and satiation was examined in a study where exercise (X) or sedentary (S) condition preceded meals of either Paleolithic (P) or Western (W) composition.

PURPOSE

Examine the effect of P and W meals and X or S on hunger and fullness ratings during postprandial periods (PPs).

METHODS

Postmenopausal women engaged in 1 of 4 conditions: S or 2 bouts of X (7–9 h and 14–16 h) with P or W meals (PS, PX, WS, WX; n=8 each) provided at 10 h and 17 h. PP hunger and satiation were measured hourly with a 100‐mm visual analog scale. Meals contained 30% carbohydrate (CHO), 25% protein (PRO), and 45% FAT in P vs 60% CHO, 15% PRO, and 25% FAT in W. Changes in hunger and satiation to X, P and W during two PPs were tested with repeated‐measures mixed model ANOVA.

RESULTS

Satiation during both PPs was unaffected by either P,W or X. Hunger ratings were significantly lower to P meals during both PPs. An additional suppressive effect of exercise during 1st PP, and an interactive effect of X during 2nd PP, was apparent but not statistically significant.

CONCLUSION

Absence of a differential effect of diet composition and exercise on the satiation suggests a role of meal volume in its control. Differential effects of diet, and possibly of exercise, on hunger ratings, suggest a sensitivity in hunger controls to variations in nutrient composition and energy expenditure.
Comparative evaluation of the results of open video endoscopic operations of patients with esophageal achalasia
Authors: Volchkova Irina
Published: June 2021

The objective of the study was to determine whether results of open and laparoscopic operations for esophageal achalasia are comparable. All patients (n = 53) were divided into two groups according to the used method of oesophagocardiomyotomia: first ‐ basic (laparoscopic) group (n = 29), in which a laparoscopic approach has been used, the second ‐ control (open) group (n = 24), in which open (laparotomy) oesophagocardiomyotomia was used.

Blockade was completely (100%) eliminated in cardioesophageal transition using the improved method of oesophagocardiomyotomia year after operation in comparison with a standard method, which had the current indicator in 79.2% of the value of all clinical cases. We observed endoscopically full antireflux effect in 96.6% operated in the first group versus 75% in the comparison group. Endoscopically positive GER was detected in 1 (3.4%) patient of the main and in 6 (25%) patients of the control group ( ƒÔ2=4,9; „Q=0,025). An improved method of laparoscopic oesophagocardiomyotomia is characterized by a more pronounced antireflux effect than laparotomy (96.6% versus 75% respectively) and by 100% removal of the disturbed patency of cardioesophageal transition versus 79.2% of the control group.
Schwann cell transplantation enhances diaphragm recovery following cervical spinal cord injury
Authors: Mercier Lynne , Arias Natalia , Gonzalez‐Rothi Elisa , Little L. Nicole , Fuller David , Muir Elizabeth , Rogers John , Bunge Mary , Lane Michael , Reier Paul
Published: June 2021

Respiratory function is compromised following cervical spinal cord injuries (cSCI) due to interruption of respiratory pathways. Peripheral nerve grafts, a source of Schwann cells (SCs), alone or in combination with other treatments have been reported to promote improved respiration after cervical hemisection. SC transplantation in a contusion model has shown to improve locomotor function. In this study, we looked at how SCs would affect respiration in a clinically‐relevant contusion cSCI model.

Adult female rats received lateralized C3/C4 contusion cSCI, leading to a rapid shallow breathing pattern (RSB). At 1 week post‐injury, animals were injected into the lesion site with SCs (~2.5 million) expressing either mCherry or green fluorescent protein (gfp). Controls were lesioned only. Animals receiving SCs were immunosuppressed. Respiratory function under eupneic and hypercapnic conditions was assessed. Histological analyses confirmed survival of SCs. Our initial findings show that RSB was absent in SC recipients, which also had improvement in diaphragm EMG activity during hypercapnia. Preliminary results with grafts of SCs expressing Chondroitinase ABC did not have any additional effect. These preliminary results suggest SCs can alone promote recovery after experimental cSCI. Identifying substrates mediating this recovery and how brainstem plasticity is affected also are under investigation.
miR‐21 Knockdown Attenuates the Cardioprotective Effects of Isoflurane
Authors: Olson Jessica , Yan Yasheng , Kriegel Alison , Bai Xiaowen , Liang Mingyu , Bosnjak Zeljko J.
Published: June 2021

Anesthetic‐mediated cardioprotection has been shown to decrease myocardial infarct size after ischemia‐reperfusion injury. Many cell signaling pathways have been investigated in this phenomenon, however, the role of microRNA remains unknown. MicroRNAs are short, non‐coding nucleotide sequences that negatively regulate gene expression through degradation or suppression of messenger RNA. Previously, we have shown that miR‐21 is upregulated approximately 2.5‐fold after exposure to isoflurane in both in vivo and in vitro rat models. In this study, we investigated the effect of knocking down miR‐21 expression on cardioprotection by isoflurane in neonatal rat cardiomyocytes.

Knockdown of miR‐21 in neonatal rat cardiomyocytes was achieved by transfection with Lipofectamine and confirmed using qRT‐PCR. Lactate dehydrogenase release assays were conducted to assess cell viability compared to scramble‐transfected controls. Our results show that miR‐21 knockdown attenuates the cardioprotective effect of isoflurane in neonatal rat cardiomyocytes. We have also shown a correlation between miR‐21 knockdown and decreased expression of pAkt, a well‐established mediator of protective cell signaling pathways. Further investigation into the mechanisms by which miR‐21 contributes to cardioprotection may offer novel insight into the attenuation of ischemia‐reperfusion injury.
Enhanced thrombus development after transient cerebral ischemia
Authors: Tang Ya Hui , Granger D. Neil
Published: June 2021

Transient ischemic attack (TIA) is a precursor event in 7–40% of patients who suffer from an ischemic stroke. This study examined whether a brief transient period of ischemia leads to an increased vulnerability of the brain to thrombus development. TIA were induced in mouse brain by occluding the middle cerebral artery for 2.5 to 10 mins. Twenty‐four hrs thereafter, mice were evaluated for neurological deficits, and thrombus formation was induced in cerebral microvessels using the light/dye method. Thrombosis was quantified using time of onset of platelet aggregation on the vessel wall and time to complete flow cessation. Compared to control mice, TIAs ranging in duration from 2.5 to 10 mins resulted in an accelerated rate of thrombus development. The TIA enhanced thrombogenesis was not accompanied by changes in neurological function or brain infarction (assessed by TTC staining). Aspirin (ASA), which is an initial line of treatment for TIA in humans, was shown to offer modest but significant protection against TIA enhanced thrombus development. Our findings indicate that TIA accelerates thrombus development in the cerebral microcirculation and that ASA treatment offers modest benefit in preventing this response.
Improvement in skeletal muscle oxidative capacity by fish oil supplementation is associated with decreased insulin resistance induced by high‐fat diet in C57Bl/6 mice
Authors: Hirabara Sandro M , Martins Amanda R , Teodoro Bruno G , Bomfim Lucas H Montes , Crisma Amanda R , Amaral Catia L , Masi Laureane N , de Sousa Luis G O , de Sousa Luis G O , Gorjao Renata , Pithon‐Curi Tania C , Silveira Leonardo R , Curi Rui
Published: June 2021

We evaluated the effects of fish oil supplementation (FOS), a source of n‐3 polyunsaturated fatty acids, on skeletal muscle insulin resistance and impaired muscle oxidative capacity induced by high‐fat diet (HFD) in C57Bl/6 male mice. Animals were divided in four groups: control diet (CD), HFD, CD plus FOS, and HFD plus FOS. FOS was given by gavage at 2 g/Kg of body weight, three times/week during 12 weeks. Our results showed increased whole‐body insulin sensitivity, reduced body weight gain and improved lipid profile in animals with FOS. Insulin‐stimulated glucose metabolism, oxygen consumption, and Akt and GSK‐3b phosphorylation in isolated soleus muscle were impaired by HFD, but FOS reduced or abolished these effects. Tricarboxylic acid cycle activity was decreased in gastrocnemius muscle by HFD, but prevented by FOS. In addition, muscle reactive oxygen species production was reduced in animals with FOS. In summary, the results suggest that the prevention of skeletal muscle insulin resistance induced by HFD with FOS is associated with improved muscle oxidative capacity. Support: FAPESP, CNPq, CAPES, Dean's Office for Research/USP, Clear, INOD, and NEL.
Losartan prevents impairment of learning and memory induced by chronic mild and unpredictable stress in rats
Authors: Sanches Andrea , Casarini Dulce Elena , Marcondes Fernanda Klein , Cunha Tatiana Sousa
Published: June 2021

We have previously shown that chronic mild and unpredictable stress (CMS) reduced learning and memory and increased renin‐angiotensin system (RAS) activity in rats. The aim of this study was to evaluate the effect of RAS inhibition on the stress induced‐learning and memory‐impairment in rats. Male Sprague‐Dawley rats were randomized into four groups: control, CMS, losartan (50mg/Kg) and CMS + losartan (n=12/group). CMS protocol consisted on application of different stressors, 7 days/week during 3 weeks. Fifteen days after CMS the Y‐maze test was performed for learning and memory evaluation. Data were analyzed by bifatorial ANOVA (p<0.05). All procedures were approved by Institutional Ethics Committee. There was a decrease in difference scores of entries on CMS group (3.0 ± 4.5%) compared with control group (21.9 ± 4.6%) and CMS + losartan group (18.0 ± 2.7%) compared to losartan group (26.7 ± 5.1). Losartan and CMS + losartan groups showed increased of entries difference score compared with control and CMS respectively. There was no difference between control and CMS + losartan group. These data suggest that RAS overactivity is at least in part involved in learning and memory impairment induced by CMS. Financial support: FAPESP, CNPq, CAPES.
Hydrogen Sulfide Induces Hyperalgesia Through potentiation of NMDA receptors
Authors: Wang Xiu‐Li , Zhao Xiaonan , Liu Peng , Li De‐Pei , Guo Yue‐Xian
Published: June 2021

Hydrogen sulfide (H2S), is an endogenous neurotrasmitter, modulates various physiological and pathological events including nociception. In this study, we investigated the role of NMDA receptors in the nociception induced by H2S in spinal cord. Intraplantar injection of an H2S donor, NaHS, into hindpaw significantly decreased the paw withdrawal threshold (PWT) latency in the contralateral hindpaw. Furthermore, NR2B mRNA and protein levels were increased in the spinal dorsal horn, but not in dorsal root ganglion (DRG) in rats subjected to NaHS intraplantar injection. Intrathecal (i.t.) injection of methemoglobin, a H2S scavenger, blocked reduction of PWT and increases expression of NR2B mRNA induced by intraplantar injection of NaHS. In addition, NaHS‐induced alteration of PWT and NR2B expression was partly, but significantly, attenuated by intrathecal injection of hydroxylamine, a CBS inhibitor, Collectively, these data suggest that peripheral administration of H2S donor causes hyperalgesia through increase in NR2B expression and production of endogenous H2S in the spinal dorsal horn.
Changes in Body Composition with Six Weeks of Resistance Training
Authors: Chen Vincent C.W. , Lee Chang Woock , Lee Teak V. , Bui Steve , Fluckey James D. , Riechman Steven E.
Published: June 2021

Purpose

Resistance exercise training has been shown to increase muscle mass. However, it is not as common to be recommended for fat loss. The purpose of this study was to examine the effects of 6‐week resistance exercise training on body composition.

Method

Eight untrained young men and women (Age=24±5, BMI=30±3) performed a 6‐week progressive whole body resistance training program, consisting of chest press, leg press, lat pull‐down, leg curl, arm curl, leg extension and triceps extension. Dual‐energy X‐ray absorptiometry (DEXA) was performed before and after training.

Results

After 6 weeks of resistance exercise training, lean mass significantly increased by 2.06±0.95% (54.55±3.03 to 55.8±3.39 kg, p=0.040), while body fat percentage significantly decreased by 5.05±1.33% (29.85±5.90 to 28.58±5.85 kg, p=0.013). There was no significant change in total body mass (87.66±6.64 to 87.63±6.64 kg, p=0.941).

Conclusion

Six weeks of resistance exercise training is sufficient to result in significant muscle gain and fat loss. While total body mass remained unchanged, body composition was improved. Therefore, resistance exercise may be recommended for the purpose of fat loss while improving muscle mass.
Effect of Hypoxic Training on Fatty Acid Oxcidation in Obese Rats
Authors: Feng lianshi , Lu yingli , Zhang li , Xu jianfang , He zihong
Published: June 2021

Objective

To study the effects of hypoxic training on fatty acid oxcidation of obese rats.

Method

130 obese rats were divided into 13 groups at random:control group, normoxic training 1,2,3,4 week group, hypoxia sedentary1,2,3,4 week group, and hypoxic training 1,2,3,4 week group. The rats in training groups ran on a treadmill for 60 min a day at 26 m/min in normoxia or 21 m/min in hypoxia(13.6%), 6 days a week for 1–4 weeks. After corresponding week, Real‐time quantitative PCR was adopted to test the expression of carnitine palmitoyl transferase (CPT‐1mRNA) in gastrocnemius and liver. Lipoprotein lipase in gastrocnemius (LPLm) and adipose (LPLa) were measured using ELISA.

Results

1)Hypoxic training 4 week significantly reduced CPT‐1mRNA in liver more than control, and even more than normoxic training (P<0.05) ;2) CPT‐1mRNA in gastrocnemius of obese rats was increased in 3–4 week (P>;0.05), and in 4th week, CPT‐1mRNA was significantly higher in hypoxic training group compared with normoxic training and hypoxia sedentary (P< 0.05) ;3) After 4 weeks, LPLa/ LPLm was lower in hypoxic training group than normoxic training group (P<0.05).

Conclusion

1)Hypoxic training increased fatty acid oxcidation of skeletal muscle more than normoxic training. 2)Hypoxic training decreased fatty acid oxcidation of liver and even more than normoxic training.

(Supported by NSFC: Grant No. 30971415)
Treadmill Exercise Represses Neuronal Cell Death And Inflammation During Amyloid beta‐Induced ER Stress By Regulating Unfolded Protein Response In Aged Presenilin 2 Mutant Mice
Authors: Kang Eun‐Bum , Kwon In‐Su , Koo Jung‐Hoon , Jang Yong‐Chul , Lee Jin , Cho In‐Ho , Lee Youngil , Cho Joon‐Yong
Published: June 2021

Alzheimer's disease (AD) is characterized by the deposition of aggregated amyloid‐beta (Aβ) in the brain, which triggers endoplasmic reticulum (ER) stress and inflammation and leads to apoptotic cell death. Growing evidence has suggested that endurance exercise is protective against neurodegenerative diseases including AD. However, the cellular mechanisms responsible for endurance exercise‐mediated brain protection against AD remain to be determined. Here, we show that treadmill exercise (TE) prevented memory impairment and reduced Aβ‐42 deposition via the inhibition of β‐secretase 1 in the brain of aged presenilin‐2 (PS2) mutant transgenic (Tg) mouse. Moreover, we found that TE inhibited ER stress‐induced unfolded protein response such as GRP78/Bip, and JNK‐p38 as well as the apoptotic pathways of the UPR such as CHOP, caspase‐12, caspase‐3 with upregulation of Bcl‐2 and downregulation of Bax in the hippocampus. Finally, TE attenuated the generation of TNF‐α and IL‐1β and the number of TUNEL‐positive cells. Collectively, these results suggest that TE will lead to important clinical benefits in the management of patients with AD and provide new insight into the mechanisms by which exercise protects the brain against AD.
Body position and backpack loading: an upright magnetic resonance imaging study of the adult lumbar spine
Authors: Shymon Stephen Joseph , Hargens Alan R. , Minkoff Lawrence A. , Chang Douglas G.
Published: June 2021

The human lumbar spine is uniquely adapted to the gravitational stress of upright posture. Using upright magnetic resonance imaging (uMRI), we characterized the adult lumbar spine's response to upright gravitational loading. We hypothesized that a gravitational load would compress the intervertebral discs (IVDs). Five volunteers underwent T2 weighted sagittal 0.6T uMRI scans of the lumbar spine while supine, upright, and upright with a 10% body weight (BW) backpack. While upright, the 10% BW load significantly compressed the L4‐L5 and L5‐S1 IVDs by about 10% relative to supine (p < 0.05). Upright posture and the 10% BW load significantly compressed the anterior L5‐S1 IVD relative to supine (p < 0.05). Gravitational loading of the lumbar spine plus an added 10% BW load compresses the caudal IVDs (L4‐L5 and L5‐S1), suggesting that these discs are either bearing more of the load or are more compliant than the other IVDs. This study is the first radiographic analysis to describe the adult lumbar spine in the upright position with added spinal load. This study was supported by the National Aeronautics and Space Administration Grant NNX10AM18G and the UCSD Clinical Translational Research Institute Fellowship Award.
Dietary cholesterol interacts with dietary fats by stimulating hepatic lipids accumulation in Ovx rats: possible defect of VLDL assembly
Authors: Côté Isabelle , Lavoie Jean‐Marc
Published: June 2021

This study was designed to evaluate the effect of dietary cholesterol level on liver lipids in the estrogen deficiency status (Ovx). Sprague dawley rats (n = 64) were assigned to one diet: standard (SD), high fat (HF), high fat/high cholesterol (HFHC (0.25%)) or HFHC (0.5%). Half of rats were Ovx or Sham‐operated (Sham) and sacrificed 6 weeks later. Liver triacyglecerol (TG) was not affected in HF fed rats but 2× increased (P < 0.01) in both HFHC compared to SD fed rats. Liver TG was increased by Ovx (37–79%; P < 0.001). Liver total cholesterol (TC) was unchanged by HF but largely accumulated in both HFHC fed rats and reached respectively 260% and 350% (P < 0.001) compared to SD values in Sham. Interestingly, these values were increased to 350 and 530% (P < 0.001) in Ovx rats. Liver microsomal transfer protein (MTP) mRNA, a key protein in very low density lipoprotein (VLDL) assembly, was largely decreased in HFHC groups (P < 0.001) and with Ovx (P < 0.001). Moreover, apolipoproteinB (apoB), diacylglycerol acyl transferase 2 (DGAT2), acyl Co‐A: cholesterol acyltransferase 2 (ACAT2), involved in VLDL assembly, were decreased (P < 0.001) with Ovx. Our data show a synergic effect of dietary cholesterol and fat on hepatic lipids and cholesterol accumulation and these responses being exacerbated by Ovx. Based on the present molecular biomarkers, hepatic steatosis induced by HFHC and Ovx might be both explained by reduced VLDL assembly.
Cardiac Autonomic Response to Saturated Fatty Meal in Overweight and Obese Young Females
Authors: Alrefaie Zienab
Published: June 2021

The present study aimed to assess the effect of saturated fatty meal on heart rate variability (HRV) in overweight and obese young females.

42 (18–23 years old) female volunteer students were included into the study. On 7th day of menstrual cycle, participants had high fat milkshakes at 8 a.m., 3 hours preceding HRV assessment.

HRV indices included; standard deviation of all R‐R intervals (SDRR), root mean squares of successive differences between R‐R intervals (rMSSD), very low frequency waves (VLF), low frequency waves (LF), high frequency waves (HF). LF/HF ratio was calculated.

The rMSSD and HF waves were significantly decreased in overweight and obese groups when compared to control group (P< 0.01, P< 0.001) and (P<0.001, P< 0.001) respectively.

The LF waves showed significant increase in overweight group (P<0.001) and significant decrease in obese group (P<0.05).

The LF/HF ratio was significantly increased in the overweight group (P<0.001), and insignificantly different in the obese group. No significant correlations were found between body mass index, waist hip ratio and HRV parameters.

The present study revealed loss of protective vagal influence on heart rate in overweight and obese young females.

Interestingly, the present study showed a blunted sympathetic response to saturated fatty meal in obese young females, while in the overweight group, sympathetic hyperactivity was observed.
Effect of isometric handgrip exercise on heart rate variability with and without somatosensory stimulation
Authors: Baker Jacquie , Shoemaker Kevin J
Published: June 2021

Sub‐motor somatosensory electrical stimulation (STIM) of skeletal muscle increases heart rate variability (HRV). Short duration (<30 sec) isometric handgrip exercise (HG) increases heart rate (HR) and decreases HRV largely through vagal withdrawal. The current study aimed to determine whether a gated effect exists when HG and STIM are combined. We tested the hypothesis that changes due to STIM would dominate over HG induced changes. Twelve volunteers (7 female; aged 24±2 yr.) performed 3 protocols: 1) four × 20s HG at 30, 40 & 50% of their maximal voluntary contraction (MVC), 2) seven × 30s STIMs, and 3) a combination of HG+STIM. Compared to rest, STIM increased HRV (Rest: 61±80ms2, STIM: 69±84ms2, p<0.05). In contrast, HRV decreased at all HG levels (ΔHRV@30%: −39±51ms2, 40%: −29±39ms2, 50%: −25±39ms2). The effects of HG were reversed during HG+STIM (ΔHRV@30%STIM: −1.7±40ms2, 40%STIM: 5.5±37ms2, 50%STIM: −4.2±19ms2, p<0.05). Heart rate did not change during STIM (Rest: 59±7bpm; STIM: 58±6bpm). However HR increased above baseline and progressively at each level of HG (50% vs. 30%, p<0.001; 50% vs. 40%, p<0.001; 40% vs. 30%, p<0.05). Heart rate was not different between HG and HG+STIM, p=0.095. The results indicate somatosensory stimulation can reverse the changes in HRV induced by handgrip suggesting muscle afferent signals may gate descending signals affecting heart rate variability. Funded by CIHR.
PACAP: A potential modulator of adrenal‐level HPA responses to acute and chronic stress
Authors: Valdez Matthew Christopher , Curras‐Collazo Margarita , Jha Vidyasagar , Kouch Justin , Spurgin Kurt
Published: June 2021

Pituitary adenylate cyclase‐activating polypeptide (PACAP) is involved in hypothalamo‐pituitary‐adrenal (HPA) responses to stress but it's role at the adrenal level is unclear. Gene markers of HPA activation were measured by qPCR using adrenal glands of C57Bl6 and PACAP knockout (KO) mice. Restraint stress (1 hr) increased adrenal PACAP (p=0.01, n=13), steroidogenic acute regulatory protein (STAR) (p=0.02, n=7) and melanocortin receptor accessory protein (MRAP) mRNA (p=0.0003, n=8). Isolation stress for 8 weeks did not impact adrenal PACAP mRNA (p=0.27, n=22). However, isolation stress in PACAP KO mice increased adrenal adrenocorticotropic hormone receptor, melanocortin 2 (MC2R) mRNA (p=0.04, n=9) and MRAP (p=0.01, n=19) but not STAR and CYP11B1, which encodes for steroid 11β‐hydroxylase. Consistent with an association between elevated HPA activity and hyperactivity, PACAP KO mice showed a significant increase in distance traveled and velocity during 1 hr open field trial (p<0.0001; n=10). These results show that PACAP participates in adrenal HPA responses to acute and chronic stress via potentially different mechanisms. Support: UCMEXUS (KS, MC), Sigma Xi Research Society (KS), and APS (VJ, MV).
Hematin Supplementation Reverses the Impaired Airway Relaxation in Neonatal Rats Exposed to Hyperoxia
Authors: Sopi Ramadan B , Zaidi Syed IA , Bexheti Sadi , Temaj Gazmend , Lajçi Azem , Jakupaj Muharrem
Published: June 2021

It was shown that hyperoxia reduces nonadrenergic noncholinergic relaxation of airway smooth muscle (ASM). Therefore, we hypothesize that increase of carbon monoxide (CO) production by supplementation of tissues with hematin will reverse the hyperoxia‐induced impaired relaxant responses. Tracheal rings were excised from rat pups 12 days old, exposed to hyperoxia or room air for seven days. In pre‐constricted tracheal smooth muscle (TSM), electrical field stimulation (EFS) was applied to induce relaxation. The preparations were supplemented with heme oxigenase (HO) substrate ‐ hematin in presence or absence of HO inhibitor tin protoporphyrin‐IX (SnPP‐IX; 100 μM), and/or soluble guanylyl cyclase inhibitor 1H‐[1,2,4]oxadiazolo[4,3‐a] quinoxalin‐ 1‐one (ODQ; 10 μM). In hyperoxic animals the relaxant responses were decreased significantly, but supplementation of tissues with hematin reversed these impaired relaxation. Inhibiton of HO by SnPP‐IX diminished this effect of hematin, whereas inhibition of guanylyl cyclase by ODQ alone or in combination with SnPP‐IX nearly abolished relaxant responses.

We conclude that increase of CO production reverses the hyperoxia‐induced impaired relaxation and this may serve as a therapeutic approach in treatment of conditions characterized with airway hyperreactivity.
Functional Role of the Single Nucleotide Polymorphism located at −224 A>;G and −599 C>;T in Neuropeptide Receptor Y2 (NPY2R) Gene in Predisposition to Hypertension
Authors: Jusino Shirley , Arroyo Nelly , Albino Elinette , Dutil Julie
Published: June 2021

Hypertension (HTN) or high blood pressure is a disease that affects one in three adults worldwide. Genetic, environmental and lifestyle factors influenced the risk of having HTN. Previous work in human population have identified genetic variants in the promoter region of the Neuropeptide Y receptor 2 (NPY2R) associated with hypertension. We hypothesized that single nucleotide polymorphism (SNP) in the promoter region of the NPY2R at −224 A>;G and −599 C>;T will affect the expression levels of this gene. To examine this hypothesis the DNA of 16 individuals were amplified to produce two fragments of 1025bp (R3) and 349bp (R4) of the regions of interest in NPY2R. These fragments were inserted into the luciferase reporter system vectors (pGL4.10 and pGL4.23 respectively) and transfected in the HEK 293 cells. Expression levels of the luciferase reporter gene were measured and compared for the different constructs. Our data provided strong evidence that both alleles (−224 A>;G & −599 C>;T) can regulated the level of expression of the promoter in NPY2R. However, the insert containing both SNPs (−599 & −224) appears to exert a greater expression in gene regulation. This may be due to the combination of both SNPs and the influence of the promoter region belonging to NPY2R.
Caveolin‐1‐Dependent Regulation of Myocardin Expression and Contractile Phenotype in Colonic Circular Smooth Muscle
Authors: Bhattacharya Sayak , Kendig Derek , Grider John , Murthy Karnam
Published: June 2021

The signaling molecules in smooth muscle are compartmentalized by binding to caveolin‐1, a key protein in the formation of caveolae. Our recent studies showed that carbachol‐induced Rho kinase activity and colonic smooth muscle contraction, and colonic propulsion were decreased in caveolin‐1 knockout (Cav‐1‐/‐) mice. The aim of this study is to test the hypothesis that caveolin‐1 acts as a pro‐contractile and anti‐proliferative regulatory molecule that promotes smooth muscle function. Expression of myocardin, a co‐activator of the transcription factor serum response factor, and microRNA‐144 that regulate smooth muscle phenotype was decreased in colonic circular smooth muscle of Cav‐1‐/‐ mice, and by silencing caveolin‐1 expression in control cultured muscle cells. Decrease in myocardin in Cav‐1‐/‐ mice was accompanied by a decrease in smooth muscle myosin heavy chain (SM‐MHC) expression and increase in EGF receptor phosphorylation and ERK1/2 activity. Treatment of muscle cells with carbachol for 24 h increased myocardin expression; the increase in expression was blocked by inhibitors of Rho kinase (Y27632) and actin polymerization (cytochalasin D), implying that changes in expression of myocardin in Cav‐1‐/‐ mice could be a consequence of the decrease in Rho kinase activity in these mice. We conclude that caveolin‐1 promotes myocardin expression and contractile phenotype via a Rho/Rho kinase pathway.
R‐Type Calcium Channels Contribute to Colonic Inhibitory Neuromuscular Transmission
Authors: Rodriguez‐Tapia Eileen , Galligan James
Published: June 2021

The inhibitory neurotransmitters, ATP and nitric oxide (NO), relax the colonic smooth muscle which is important for propulsion of colonic content. Voltage‐gated Ca2+ channels (VGCC) control neurotransmitter release and regulate colonic motility. The α1E subunit of the R‐type VGCC is expressed by enteric neurons yet its role in regulating colonic motility is unclear. We investigated the role of R‐type VGCCs in colonic inhibitory neuromuscular transmission using alpha1E knockout (KO) mice. Intracellular recordings of inhibitory junction potentials (IJP) were obtained from circular muscle cells in distal colon. IJPs were evoked by trains of electrical stimulation (1s, 10 Hz, 40‐90 volts). IJPs have a fast ATP‐mediated component and a slow NO‐mediated component. Peak amplitude (ATP component) and area under the curve (AUC; both components) of the IJP were compared between wildtype (WT) and KO mice. Resting membrane potential (RMP) was measured as an index of ongoing inhibitory transmission. There was a voltage dependent increase in IJP amplitude and AUC in WT and KO mice. IJP amplitude was similar in WT and KO mice. The IJP AUC was decreased in KO compared to WT. Nifedipine (1 µM; L‐type VGCC blocker) had no effect on these responses. RMP in KO muscle cells was decreased compared with WT (‐44 ± 2 mV in WT and ‐38 ± 1 mV in KO; P < 0.05). Thus, there was a 5.4 mV RMP depolarization in KO mice. Nifedipine did not change RMP of WT or KO cells (‐39 ± 3 mV, WT and ‐40 ± 1 mV in KO). In conclusion, R‐type VGCCs contribute to colonic inhibitory neuromuscular transmission by controlling NO release. In addition, R‐type VGCCs contribute to ongoing release of NO and ATP which maintain colonic muscle tone.
Neuropeptide S Reduces Gut Motility in Rats and Humans
Authors: Saudi W S W. , Halim M A. , Webb D.‐L. , Hellström P M. , Sjöblom M.
Published: June 2021

The actions of NPS on intestinal motility and duodenal mucosal barrier function in anaesthetized rat in vivo and human circular muscle strips in vitro were elucidated in this study.

A segment of the proximal duodenum or descending colon with an intact blood supply of male Sprague‐Dawley rat was perfused in situ. The effects of intravenous (i.v.) administration of neuropeptide S (NPS) and NG‐nitro‐L‐arginine methyl ester (L‐NAME) were investigated on intestinal motility and duodenal mucosal paracellular permeability. The influence of NPS on ethanol‐induced changes of duodenal mucosal bicarbonate secretion (DBS) was studied. Normal human circular colonic muscle strips were studied in organ bath. Tension changes were measured after NPS administration, NPS challenge with L‐NAME, tetrodotoxin (TTX) or stimulated with EFS. Values are mean ± SEM, compared by 1‐ or 2‐way ANOVA or paired t test when appropriate.

NPS decreases both small intestinal and colonic motility but increases duodenal paracellular permeability. Pre‐treating animals with the non‐selective NOS inhibitor L‐NAME abolished the effect of NPS on duodenal motility but not on permeability. NPS reduces ethanol‐induced increases in DBS. In the human colonic smooth muscle strip, NPS dampened contractility with or without electrical field stimulation, which abolished by administration of L‐NAME and TTX.

NPS inhibits gastrointestinal motility in animal and man, most likely via a neural nitric oxide (NO) release. To this end, NPS increases paracellular permeability may represent an early step of inflammatory response.