bluuebunny/crossref_metadata_2025_split huggingface dataset:
Insulin ameliorates myocardial inflammation and promotes recovery of T cell in murine experimental autoimmune myocarditis
Authors: Zhang Yuan , Zhuang Ran , Geng Chaoqun , Tian Na , Cai Xiaoqing , Lei Wen , Gao Feng 
Published: June 2021

AimGlucose‐insulin‐potassium is a useful adjunct to myocarditis. Besides its essential action in energy metabolism, insulin also exerts an anti‐inflammatory effect. This study investigated the effect of insulin on myocardial inflammation in experimental autoimmune myocarditis (EAM) mice and its underlying mechanisms.MethodsBALB/c mice were immunized subcutaneously with myocarditogenic peptide MyHC‐a and randomly divided into mock‐immunized, saline‐treated and insulin‐treated groups. T lymphoma cell line EL4 was used for in vitro study.ResultsInsulin reduced pro‐inflammatory cytokine IL‐1β with no changes of blood glucose and autoantibody production. Inflammatory infiltrates were less abundant in insulin‐treated hearts than those in saline‐treated hearts on day 21 after immunization. Meanwhile, insulin significantly reduced sera cTnI of EAM mice on day 14 and 21 (P<0.05). Interestingly, insulin promoted T cell recovery. CD3+ T cells in insulin‐treated mice proliferated more vigorously than those in saline‐treated mice without changing the memory/naïve T cell ratio. Moreover, ERK1/2 inhibitors blocked the insulin‐induced EL4 cells proliferation.ConclusionsThese data suggest that insulin exerts an anti‐inflammatory action in EAM and increases T cell proliferation by activating ERK1/2.Supported by the State Key Program of National Natural Science Foundation of China (No. 81030005)
Lower body muscle tensing is an effective countermeasure to initial orthostatic hypotension induced cerebral hypo‐perfusion upon standing from a squatted position
Authors: Walsh Jeremy J , Bentley Robert F , Kellawan J Mikhail , Tschakovsky Michael E 
Published: June 2021

PURPOSEto examine the effects of 5 s of lower body muscle tensing (LBMT) after rising from squat on middle cerebral artery blood velocity (MCABV) following a squat‐to‐stand protocol.METHODSHealthy subject (n =8; 24.4 ±1.9 yrs) performed a squat‐to‐stand protocol. Upon standing participants performed either no manoeuvre (Control) or LBMT which was held for 5 s. MCABV (cm/s; surrogate for cerebral perfusion) was measured with transcranial Doppler ultrasound (TCD), mean arterial pressure (MAP) via finger photoplethysmography. Cerebral blood pressure (CBP) was calculated by measuring the hydrostatic column from the heart (MAP) to the TCD probe. Cerebral vascular conductance (CVC) was calculated from MCABV and CBP.RESULTSData are mean ±SD. The drop in MAP upon rising from squat was −15.8 ±3.9 mmHg in Control vs. −6.02 ±10.5 mmHg in LBMT, p < 0.05. This represented a 62% attenuation of hypotension via LBMT. MCABV decreased by −11.8 ±3.07 cm/s in Control vs. −3.72 ±4.48 cm/s in LBMT, P <0.05, which represents a 68% attenuation of cerebral hypo‐perfusion.CONCLUSIONSLBMT for the first 5 s upon rising from squat is an effective countermeasure for minimizing cerebral hypo‐perfusion. NSERC.
Enhanced external counterpulsation (EECP) increases GLUT‐4 protein expression, capillary density and glucose tolerance in patients with abnormal glucose tolerance
Authors: Martin Jeffrey S , Beck Darren T , Aranda Juan M , Braith Randy W 
Published: June 2021

We sought to evaluate the effects of EECP therapy on outcomes of glucose tolerance and skeletal muscle morphology in patients with abnormal glucose tolerance (AGT).MethodsEighteen patients with AGT were randomly assigned (2:1 ratio) to receive either 7 weeks (35 1‐hour sessions) of EECP (n = 12) or 7‐weeks of standard care (control; n = 6). Biochemical assays, oral glucose tolerance, and skeletal muscle morphology were assessed before and after EECP or control.ResultsFollowing EECP, plasma vascular endothelial growth factor (VEGF) was increased (9.74 ± 1.59 to 17.04 ± 2.65 pg/mL, P<0.05). Vastus lateralis skeletal muscle biopsies demonstrated improvements in capillary density (454 ± 21 to 497 ± 19 mm−2, P<0.05) following EECP. There was no change in glucose uptake signaling pathways, but total GLUT‐4 protein expression was elevated (+47%, P<0.05) following EECP. Fasting (−16.9 ± 5.4 mg/dL) and 120‐min (−28.3 ± 7.3 mg/dL) plasma glucose from oral glucose tolerance testing were also improved following EECP (P<0.05). Further, the Matsuda index, a whole‐body composite insulin sensitivity index, increased (+21%, P<0.05).ConclusionsEECP mediated increases in capillary density and GLUT‐4 in patients with AGT paralleled improvements in surrogates of insulin sensitivity and glucose tolerance.This research was supported by the Department of Applied Physiology and Kinesiology at the University of Florida.
IRE1‐alpha signaling can be related to palmitate‐induced insulin resistance in L6 myotubes
Authors: Silva Patricia Ebersbach , Poletto Ana Claudia , Anhe Gabriel Forato , Machado Ubiratan Fabres 
Published: June 2021

Recent studies showed that elevated free fatty acids (FFAs) can induce endoplasmic reticulum (ER) stress, and this, in turn, plays a role in the development of insulin resistance (IR). This work aimed to verify the effects of palmitate on GLUT4 and ER stress proteins in L6 cells. GLUT4, IRE1‐alpha and TRAF2 proteins were analyzed in myotubes treated with 0,75mM of palmitate during 1 to 12 hours. The results showed that palmitate caused a significant reduction of the GLUT4 protein content in all treatment periods (control: 99.99±4.3, 2 hours: 66.37±7.2*, 4 hours: 65.03±8.0*, 6 hours: 67.16±8.8*, 12 hours: 58.88±5.5*), the analysis also showed an increase of IRE1‐alpha protein within 4 hours of incubation (control: 100.00±0.0, 4 hours: 184.16±49.45*) and an important increase of TRAF2 protein at the first hour of treatment (control: 100.00±0.0, 1 hour: 125.20±9.07*). Results were expressed in arbitrary units, n=4 to 6, *P<0.05. These data showed that palmitate impaired GLUT4 expression what is preceded by activation of IRE1alpha/TRAF2 pathway. This data reinforces the proposition that FFA‐induced ER stress is associated with IR probably by reducing GLUT4 content through mechanisms not fully identified.Support: Fapesp 2010/09984‐5
Mammalian target of rapamycin regulate kidney oxygen consumption by controlling mitochondrial function via regulation of uncoupling protein 2
Authors: Sivertsson Ebba , Friederich Malou , Palm Fredrik 
Published: June 2021

Excessive kidney oxygen consumption (QO2) without concomitantly increased delivery results in tissue hypoxia, which is a common pathway to the development of kidney disease, including diabetic nephropathy. Mammalian target of rapamycin (mTOR) regulates cell proliferation but also mitochondrial function. However, the role for kidney QO2 is presently unknown. We therefore investigated in vivo QO2 and also studied specific mechanisms using isolated mitochondria from control and diabetic rats.Control and streptozotocin‐diabetic rats were administered rapamycin (0.15 mg/day) for 14 days. Kidney function was measured under Inactin anesthesia.Inhibition of mTOR increased kidney QO2 (+121% and +31%) and decreased tubular transport efficiency (−50% and −36%) in both controls and diabetics without affecting glomerular filtration rate. mTOR inhibition increased QO2 of isolated mitochondria by inducing uncoupling via uncoupling protein‐2.In conclusion, mTOR inhibition increases kidney QO2 by inducing mitochondrial uncoupling, which may aggravate tissue hypoxia. Thus, mTOR inhibition in patients with pre‐existing nephropathy may accelerate the progression of disease.
Drug transporter expression and function in primary cultures of human renal epithelial cells
Authors: Jenkinson Sarah Elizabeth , Brown Colin 
Published: June 2021

Primary epithelial cell cultures are an important model for studying drug transporters in vitro. They can be used as a replacement for animal models and possibly are more suitable due to variation in transporter expression between animal and human tissue. The aim of this study was to validate the use of primary epithelial cell cultures as a model for studying drug transporter expression and function in human kidney.Primary epithelial cells were isolated from human kidney tissue samples and cultured for 7 to 10 days. qPCR was used to determine mRNA expression of key transporters in the primary cells. Cells were grown on permeable filter supports to create polarised monolayers and transport of a range of radio‐labelled compounds was tested across the cell monolayers. Dye retention assays were used to determine the presence of functional efflux transporters.Expression of mRNA for a range of prototypic transporters including OCT‐2, MDR1 and MRP was confirmed. Basolateral to apical transport of various compounds including metformin and indomethacin was shown suggesting possible elimination via the kidney. Hoechst 33342 retention assay showed expression of functional MDR1. CMFDA dye retention assay showed presence of MK571 sensitive transporters, likely to be MRPs. These findings show that primary cell cultures are a good model for studying drug transporter expression and function in human kidney.
Plasma Aldosterone Levels Increase After Cerebral Ischemia and Mineralocorticoid Receptor Antagonism at the Time of Reperfusion Reduces the Size of the Infarct
Authors: Dams Carla Maria , Sinclair Elaine Bliley , Dorrance Anne McLaren 
Published: June 2021

Ischemic stroke causes blood brain barrier (BBB) breakdown by an unknown mechanism. Upregulation of tight junction proteins Claudin‐5 (CLN‐5) and Occludin (OCC) is linked to increased BBB permeability with hypoxia. Chronic MR antagonism reduces stroke damage but the acute effects of antagonism are unknown. We hypothesized that aldo increases post‐stroke, and acute MR antagonism reduces damage by regulating CLN‐5 and OCC. Wistar Kyoto (WKY) rats had 2 hours (h) of middle cerebral artery occlusion (MCAO) and reperfusion (R) (n=8), control rats had sham surgery (CON; n=4). Plasma was collected before and, 6 and 48 h post‐surgery. Aldo, measured by ELISA was increased 6 h after MCAO (848±60 vs 449±87 pg, MCAO vs CON, p<0.05) and remained elevated at 48 h (1104±48 vs 625±100, MCAO vs CON, p<0.05). To study acute MR inhibition, WKY rats had 3 h of MCAO and 45 h of R. Spironolactone (SPIR; 25mg/kg I.P.) was given at R (n=11), CON rats received vehicle (n=11). SPIR reduced the infarct size. CLN‐5 mRNA expression, assessed by qRT‐PCR was reduced by SPIR; OCC mRNA unchanged. Interestingly, OCC and CLN‐5 protein expression were decreased by SPIR. These data suggest that aldo increases after stroke and MR inhibition may prevent the damage caused by ischemia by maintaining BBB integrity

Protein
mRNA

%HI
CLN‐5
OCC
CLN‐5
OCC

SPIR
25.7±3.5*
0.2±0.1*
2.2±0.3*
0.2±0.04*
0.2±0.1

CON
35.1± 5.0
0.6±0.1
5.8±1.3
0.4±0.1
0.4±0.04

Mean±SE,
p<0.05
Physiological basis of poorer respiratory outcomes for males following preterm birth
Authors: Harding Richard , Ishak Noreen , Hanita Takushi , Sozo Foula , De Matteo Robert 
Published: June 2021

Our aim was to identify the physiological basis for the “male disadvantage” in respiratory function in preterm infants, using an ovine model of preterm birth in which survival of males is less than in males. At ~125 days of gestation (DGA; term ~147DGA), fetal sheep underwent preparatory surgery. Ewes received lowdose betamethasone (5.7mg i.m.) at 131DGA. At 133DGA, lambs were delivered via caesarean section and were studied for 8 hours with no ventilatory support. Arterial and intrapleural pressures were recorded continuously and arterial blood was sampled every 15min. Lambs were then euthanized for static lung compliance measurement. At 6–8h after preterm birth, males had significantly lower arterial pH and higher PaCO2 than females (p<0.05). No differences were observed in lactate, glucose and mean arterial pressure. Static lung compliance was 30% lower in males than in females (p=0.012). There was a positive correlation between static lung compliance and mean pH (from 6–8h) and a negative correlation with mean PaCO2 (both p<0.05). Male preterm lambs have stiffer lungs than females at the same gestational age, leading to CO2 retention and acidemia, and is the likely cause of the “male disadvantage”. The lower lung compliance of males is likely a result of differences in surfactant composition.Funding was provided by the National Health and Medical Research Council of Australia.
Biological sex and tympanic dehiscence
Authors: Bilal Alina Susana , Jelaca-Tavakoli Maria 
Published: June 2021

In this study, the presence of tympanic dehiscence is studied using 72 trephined Peruvian crania (39 male and 33 female) from the Hrdlicka Collection housed at the San Diego Museum of Man. The objective of this study is to determine whether tympanic dehiscence alone could be used to determine sex in human osteological remains. The analysis of the tympanic plates shows that 41 or 57% of the 72 crania have the trait. From the 41 crania with tympanic dehiscence, 19 are male and 22 are female or 46% and 54% respectively, suggesting that tympanic dehiscence is more likely to occur in females. However, because of the significant number of males possessing the trait, tympanic dehiscence cannot be used alone as a reliable sex‐determining feature. Therefore, it is suggested that for accurate results, anatomists and biological anthropologists should only use tympanic dehiscence to determine sex if it is used in collaboration with other skeletal features. San Diego Museum of Man.Grant Funding Source : N/A
Vascular Variation in the Triangular Interval of the Axilla
Authors: Feldman Eleanor Jane , Shukla Anand , Marquez Samuel 
Published: June 2021

The anatomical gateways that allow the neurovascular structures to course between the axilla and posterior body regions are considered clinically important in surgeries. The triangular interval has gained considerable popularity with the increase in use of the motor branches of the triceps muscle for muscle transfers. The radial nerve and profunda brachii artery are the contents traditionally described residing in the triangular interval. To document the inherent variation found in this particular gateway, this study surveyed 40 triangular intervals from 20 donor bodies, representative of an urban population, in order to investigate the path of the radial nerve and the profunda brachii within the axilla. Results show that in 100% of the subjects, the radial nerve coursed deep to the triangular interval. Variation in the path of the profunda brachii, however, was observed. In 12.5% of the sample the profunda brachii was observed deep to the quadrangular space and not in the triangular interval. Bilateral asymmetry was observed within 60% of the variable triangular intervals. These findings demonstrate the highly variable nature of the profunda brachii's path within the axilla between as well as within individuals.Grant Funding Source : SUNY Downstate
A Novel Structure Potentially Associated with Greater Trochanteric Pain Syndrome
Authors: Taylor Victor , Crofford Theodore , Seidel Hudson , Reeves Rustin 
Published: June 2021

PurposeGreater trochanteric pain syndrome (GTPS) is commonly diagnosed, and is thought to be at least in part caused by repetitive friction between the greater trochanter (GT) and iliotibial tract (ITT). We propose that the ITT has an important insertion into the proximal femur, the ITT‐ Femoral Insertion (ITT‐FI), which is the major contributor to this friction, rather the tibial extension of the ITT.MethodHips (n=20) were dissected on embalmed cadavers. The ITT‐FI was identified as the ligamentous structure remaining after excising the gluteus maximus (GM) and tensor fasciae latae (TFL) muscle fibers from the ITT, transection of the ITT at mid femur, leaving the ITT origin at the iliac crest and insertion on the femur (near the GM) intact. Measurements recorded include: length from the iliac crest to the femoral insertion of the ITT, the width of the ITT‐FI fibers, and the relative width of the pelvis as determined by the distance from anterior superior iliac spine (ASIS) to ASIS. Photographs were taken.ResultsThe proposed structure originates at the iliac crest and inserts inferior to the GT. The pressure between the ITT and the GT changed little if at all as palpated before and after isolating the ITT‐FI. Average measurements of the structure in length was 21.3cm, and width at the iliac crest was 4.6cm. Average width of the pelvis was 25.3cm.ConclusionThe femoral insertion of the ITT is identified, measured in dimension, and appears to be the chief cause of ITT static pressure on the GT. Future studies are needed to quantify this assertion.Grant Funding Source: none
Fenestrations of the Aortic Valve Cusps: An Anatomical Explanation?
Authors: Losenno Katie L , Johnson Marjorie , Chu Michael W A 
Published: June 2021

Fenestrations of the aortic cusps are a common finding in older adults. In most cases, they are benign although there are reports of spontaneous rupture and acute onset of aortic insufficiency. The process of fenestration development is poorly understood however, it is possible that variation in cuspal anatomy may be an important factor. The aortic valves from 40 adult cadaveric specimens were harvested and examined for fenestrations. The cuspal height, free margin length, and attached margin length were measured and leaflet perimeter and area were calculated. 37.5% of all specimens were found to have aortic valves with at least one fenestrated cusp. Of those with fenestrations, 73.3% were in the left coronary cusp, 53.3% were in the right coronary cusp and 33.3% were in the non‐coronary cusp. Preliminary data suggests that cusps with a smaller perimeter are more prone to fenestrations. Previous studies have suggested that the, often larger, non‐coronary sinus and cusp are subject to greater stresses during the cardiac cycle which in turn leads to increased collagen deposition within the cusp. Although counterintuitive to the increased stresses, the non‐coronary aortic cusps in this series had less fenestrations, perhaps suggesting that increased stresses may actually prevent fenestration development. The initial findings warrant further investigation with a larger sample size and further statistical analysis.Grant Funding Source: Queen Elizabeth II Graduate Scholarship in Science and Technology
Fatty Marrow and Increased Loaded Cancellous Bone was Resistant to OVX induced Bone Changes in Female Rats
Authors: Lin Zhiming , Tian Xiaoyan , Chen Daihe , Lin Jin , Chen Min , Liu Jonathan , Shi Hexiu , Men Ping , Liu Gang , Jee Webster 
Published: June 2021

ObjectivePrevious studies determined ovariectomy (OVX) induced cancellous bone loss and raised cage (RC) bipedal stance partially prevented OVX induced bone loss at red marrow bone sites in adult rats; however, these effects in the distal tibial metaphysis (DTM) with fatty marrow, a site similar to adult long bone metaphyses (non‐veterbral bone sites) with low risk of postmenopausal fracture, have yet to be determined.MethodsSix‐month‐old female S‐D rats were divided into basal, sham, OVX, RC and combination of OVX plus RC exercise for 4 and 8 weeks, cancellous bone histomorphometry on fluorescent labeled undecalcified cross sections of DTM were performed.ResultsIn DTM, OVX did not induce cancellous bone loss, but significantly increased bone turnover. RC exercise alone had no effect on cancellous bone mass, but significantly reduced bone resorption. Unlike in high turnover red marrow sites, the combination of RC exercise and OVX only partially prevented bone loss, but combining with raised cage exercise and OVX in DTM totally inhibited OVX induced cancellous bone loss by depressing bone resorption (reduced eroded perimeter).ConclusionsIn DTM, the inhibition of OVX induced bone loss can be attributing to a combination of fatty marrow content and increased mechanical loading with decreased resorption, which may partly explain why non‐vertebral bone sites are less at risk to fracture in postmenopausal patients.
WT1 Interacts with p53 and Inhibits p53‐induced p21 gene expression
Authors: Ko Kyoung-Won , Choe Yun-Jeong , Lee Sun-Young , Kim Ho-Shik 
Published: June 2021

Wilms’ tumor suppressor gene 1 (WT1) encodes a transcription factor important for normal cellular development and cell survival. Previous studies have reported both physical and functional interaction between the WT1 and p53 proteins. However, the relationship between WT1 and p53 has not yet been fully clarified. Here we show that WT1 retards p53‐induced transcriptional activation of p21.Using domain deletion mutant constructs of p53, we determined that C‐terminal region containing DNA‐binding domain of p53 was necessary for the interaction between WT1 and p53. In osteosarcoma U2OS cells, WT1 enhanced cell death by nutlin‐3, an antagonist of MDM2, and restrained p53‐mediated p21 expression. Consistently, p53‐induced transactivation of p21 was attenuated by WT1. Moreover, small interfering RNA‐mediated knockdown of p21 expression enhanced nutlin‐3‐induced cell death. Taken together, WT1 interacts with p53 and inhibits p53‐ induced p21, leading to potentiation of p53‐induced cell death.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‐ 0027115).
The role of PHLPP in regulating cell migration in pancreatic cancer
Authors: Smith Alena , Gao Tianyan 
Published: June 2021

Pancreatic cancer is the fourth leading cause of cancer in the United States. However, it has the worse prognosis of any malignancy with a 4% 5 year survival rate. Contributing factors include but not limited to late stage diagnosis due to vague symptoms and the degree of aggression associated with this type of cancer. Surgical resection is impossible in 50% of cases due to the advanced stage at the time of diagnosis. Pancreatic Ductal Adenocarcinoma (PDA) has a high rate of chemotherapy and radiation resistance increasing the need for innovative treatment modalities. Hyperactivation of PI3K/Akt pathways is commonly associated with many types of human cancers including pancreatic cancer. Recently, we have identified a novel protein phosphatase, PHLPP (PH domain Leucine repeat Protein Phosphatase) that dephosphorylates Akt and terminates Akt signaling directly. Our previous studies show that loss of PHLPP expression results in an increase in cell proliferation and a decrease in apoptosis. Here, we investigate the role of both PHLPP isoforms namely PHLPP1 and PHLPP2 in regulating pancreatic cancer cell migration and metastasis. Stable pancreatic cancer cell lines were generated using lentivirus‐based shRNAs to knockdown endogenous PHLPP expression. Alteration of Akt‐mediated signaling is analyzed in PHLPP knockdown cells. In addition, cell migration and invasion assays are performed to determine if loss of PHLPP expression promotes both tumorigenesis and metastasis in pancreatic cancer. The knowledge gained in these studies will provide a novel therapeutic avenue using PHLPP as a potential target.Funded by NIH R01CA133429, and American Cancer Society RSG0822001TBE.