bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of 6‐weeks voluntary wheel running on the sex‐hormone and cytochrome P450 aromatase of high‐fat feeding impuberism male SD rats (884.12)
Authors: Yan Yi , Xie Minhao , Sun Jinquan , Zhao Yan 
Published: June 2021

To compare the levels of sex hormone and cytochrome P450 aromatase in gonad and extragonadal tissues of high‐fat feeding and normal diet SD rats in response to 6‐weeks voluntary wheel running.METHOD:3‐weeks SD rats were randomly assigned to normal diet sedentary(C, n=10), normal diet exercise(E, n=10), high‐fat diet sedentary(D, n=10), high‐fat diet exercise(ErD, n=10) groups. After 2‐weeks adaption, rats of E and ErD group were individually placed into the wheel‐cage to do voluntary wheel running,1 hour each half day, 5days per week for 6 weeks. Food intake and running distance were monitored daily and body weigh weekly. Serum lipids, testosterone and estradiol were determined. The protein expression of P450arom was analyzed by immunohistochemical method.RESULTS:There were significant negative effects of high‐fat diet on serum lipids, testosterone and estradiol (P0.05). High‐fat diet significantly increased the expression of P450arom in testis, quadriceps femoris (P<0.05), liver and kidney (P<0.01), but the P450arom in cardiac muscle was significantly low (P<0.05); 6‐weeks voluntary wheel running could improve these changes.CONCLUTION:Long term high fat diets have a negative impact on metabolism of sex hormone. 6 weeks voluntary wheel running can improve the sex hormone metabolism disorders induced by high fat diets, through decreasing the expression of P450arom in gonad and extragonadal tissues.Grant Funding Source: National Natural Science Foundation of China
Exercise capacity and ventilatory efficiency with afferent blockade in heart failure (884.3)
Authors: Keller‐Ross Manda , Johnson Bruce , Joyner Michael , Eisenach John , Curry Timothy , Olson Thomas 
Published: June 2021

Increased locomotor muscle afferent feedback may be linked to the reduced exercise capacity (peak VO2) and poor ventilatory efficiency (high VE/VCO2 slope) observed in heart failure (HF). We examined the relationship between peak VO2 and change in VE/VCO2 with afferent inhibition during exercise in HF. 9 HF (60±6 yr) and 9 controls (CTL) (63±7 yr) completed 3 visits. Visit 1: cycle exercise to volitional exhaustion. Visits 2‐ 3: 5 min constant‐load cycling (65% of peak work) randomized to lumbar intrathecal fentanyl injection (afferent block) or placebo. VO2, ventilation (VE), carbon dioxide production (VCO2), and end‐tidal CO2 (PETCO2) were measured. In HF, peak work (120±34 vs 176±54 W, p<0.05) and VO2 (18.4±2.7 vs 27.2±4.7 ml/kg/min, p<0.05) were reduced, whereas VE/VCO2 slope was elevated (39.7±1.8 vs 35.3±0.8, p<0.05) compared with CTL. With afferent inhibition, HF patients had a greater reduction in VE/VCO2 (‐18.8±8.1 vs ‐5.4±13.3%, p<0.05) and increase in PETCO2 (20.3±10.5 vs 6.1±9.5%, p<0.01) during constant‐load cycling. Lower VO2peak was related to a greater decline in VE/VCO2 and rise in PETCO2 after afferent inhibition in HF (r=0.82, p<0.01 and r=‐0.69, p<0.05, respectively) but not CTL (p>0.05). Our data demonstrate that patients with the lowest VO2peak have the greatest improvement in VE/VCO2, suggesting a close link between afferent feedback, ventilatory efficiency and exercise capacity in HF.Grant Funding Source: Supported by AHA 12GRNT11630027 and National Center for Advancing Translational Science KL2TR000136.
Kidney injury molecule‐1 mediates endocytosis of albumin in renal proximal tubule (892.40)
Authors: Zhao Xueying , Zhang Yuanyuan , Emmett Nerimiah 
Published: June 2021

Kidney injury molecule‐1 (Kim‐1) is a scavenger receptor that is upregulated in proximal tubule epithelium in diabetic kidney disease. In this study, we examined the cellular location of Kim‐1 in proximal tubule cells and its role in renal handling of filtered protein. Immunostaining of primary mouse kidney tubular cells revealed that Kim‐1 was expressed in the plasma membrane and also prominent in the intracellular vesicles. An increase in binding and internalization of albumin was observed in both primary cultured tubular cells expressing endogenous Kim‐1 and the rat kidney cell line (NRK‐52E) overexpressing exogenous human Kim‐1. Kim‐1‐induced albumin accumulation was abolished by its specific antibody. Moreover, internalized proteins traffic through endosomes and are delivered to the lysosome for degradation in a clathrin‐dependent pathway. Supportive evidence includes a) detection of Kim‐1 in Rab5‐positive early endosomes, Rab7‐positive late endosomes/multivesicular bodies, and LAMP1‐positive lysosomes, b) colocalization of Kim‐1 and clathrin in the intracellular vesicles, and c) inhibition of Kim‐1‐mediated albumin uptake in the presence of chlorpromazine. In primary cultured tubular cells, the expression of Kim‐1 was significantly increased when exposed to elevated albumin concentration in culture medium. Taken together, our data indicate that Kim‐1 mediates albumin uptake in renal tubular epithelial cells, at least partly through a clathrin‐dependent mechanism. Kim‐1 may represent a potential therapeutic target in proteinuric nephropathy.Grant Funding Source: Supported by the NIH SDK096441 and NIH/NCRR/RCMI 5G12RR03034‐23
Renal phenotype of inwardly rectifying potassium channel Kcnj16 (Kir 5.1) knockout in the Dahl salt‐sensitive rats (893.16)
Authors: Palygin Oleg , Levchenko Vladislav , Lowing Andrea , Ilatovskaya Daria , Pavlov Tengis , Geurts Aron , Jacob Howard , Staruschenko Alexander 
Published: June 2021

The inward‐rectifying channels play an important role in the control of resting membrane potential and tubular homeostasis in the kidney. To illuminate the importance of Kcnj16 (Kir 5.1) in the context of a disease state in vivo, we generated a Kcnj16 knockout rat model in Dahl salt‐sensitive (SS) background by using zinc finger nuclease (ZFN) technology. ZFN against Kcnj16 caused a 18‐bp in‐frame deletion that occurred in the second protein transmembrane domain. IHC analysis demonstrated highly specific expression of Kcnj16 on the basolateral membranes of cortical collecting ducts and distal convoluted tubules in the control kidneys of SS and Sprague Dawley rats, which was completely abolished in Kcnj16‐/‐ rats; thus, successful knock out of this protein and consequent degradation of the channel in renal tubules were shown. The mean arterial pressure was significantly lower in Kcnj16‐/‐ compared to wild type SS rats (91.3±1.8 to 104.7±5.5 mmHg) when animals were fed a low salt (0.4%) diet. BUN, potassium and magnesium plasma concentrations were significantly modulated in knock out rats. Urea electrolyte balance was also disturbed compared to wild type animals. Importantly, change of the diet to high salt (4%) chow resulted in mortality of KO rats within 1‐2 days. These data demonstrate critical role of Kcnj16 channels in renal salt handling and in the development of salt‐sensitive hypertension.Grant Funding Source: Supported by NIH HL108880 and ADA 1‐10‐BS‐168 to A.S., NHLBI 5RC2HL101681 to H.J.J
Signaling through the cardiac Na/K‐ATPase/phosphoinositide 3‐kinase IA pathway: role in ouabain‐induced protection against ischemia/reperfusion injury (893.31)
Authors: Duan Qiming , Kalisz Jennifer , Pierre Sandrine 
Published: June 2021

Acute myocardial infarction (AMI), the clinical manifestation of ischemia‐reperfusion (IR) injury, is a leading cause of death worldwide. Like ischemic preconditioning (IPC) induced by brief episodes of ischemia and reperfusion, ouabain preconditioning (OPC) induced by activation of Na/K‐ATPase signaling protects the heart against IR injury. PI3K‐I activation is required for IPC, but its role in OPC has not been investigated. The hypothesis that OPC and IPC rely on distinct PI3K‐I isoforms was tested. In Langendorff‐perfused mouse hearts, OPC was initiated by 4 min of ouabain 10μM and IPC by 4 cycles of 5 min ischemia and reperfusion prior to 40 min of global ischemia and 30 min of reperfusion. Without affecting PI3K‐IB, ouabain doubled PI3K‐IA activity and Akt phosphorylation. The PI3K‐IA inhibitor PI‐103 (100 nM) blocked ouabain‐induced Akt activation but not a PKCε translocation previously shown to be critical for OPC. IPC and OPC significantly preserved cardiac contractile function and tissue viability as evidenced by improved recovery of left ventricular developing pressure and end‐diastolic pressure, reduced lactate dehydrogenase release, and decreased infarct size. OPC protection was blunted by PI‐103 but not by the PI3K‐IB inhibitor AS‐604850 (1 μM). In contrast, IPC‐mediated protection was not affected by PI‐103 but blocked by AS‐604850. These data suggest that PI3K‐IA activation is required for OPC but does not regulate the previously shown PKCε translocation. The finding that OPC and IPC pathways rely on distinct PI3K‐I isoforms may be of clinical relevance in AMI patients presenting with diseases and medications that impact PI3K‐IA and IB differently.Grant Funding Source: Supported by HL‐36573
Ablation of intestinal brush‐border Na+/H+ exchanger NHE3 impairs iron absorption in the mouse (900.1)
Authors: Shawki Ali , Engevik Melinda , Kim Robert , Anthony Sarah , Knight Patrick , Baik Rusty , Worrell Roger , Shull Gary , Mackenzie Bryan 
Published: June 2021

Divalent metal‐ion transporter‐1 (DMT1) is critical for intestinal iron absorption. DMT1 is energized by the H+ electrochemical potential gradient but the provenance of the H+ required to drive apical iron uptake is not known. To assess the role of the brush‐border acidic microclimate in aiding intestinal iron transport, we have examined iron homeostasis and intestinal iron handling in mouse models lacking the brush‐border Na+/H+ exchangers NHE2 and NHE3. We found that liver nonheme iron stores (a preferred indicator of chronic iron status) were modestly depleted in NHE2‐null mice compared with wildtype mice. In animals stressed on a low‐iron diet, hematological and blood‐iron variables were no different between NHE2‐null and wildtype mice and we observed no difference in the expression of genes associated with iron metabolism. Liver nonheme iron stores were severely depleted (by 70–90%) in NHE3‐null mice compared with wildtype mice. We observed substantial decreases in serum iron and transferrin saturation in NHE3‐null mice but no overt anemia. mRNA expression of DMT1, the brush‐border ferrireductase Cybrd1, and the basolateral iron‐exporter ferroportin were each increased >10‐fold in NHE3‐null mice, and expression of liver Hamp1 (hepcidin) suppressed by over 99%, compared with wildtype. Absorption of 59Fe (administered by intragastric gavage) was profoundly impaired in NHE3‐null mice but not NHE2‐null mice compared with wildtype. The low 59Fe content of enterocytes in the NHE3‐null revealed a deficit in brush‐border iron uptake. Our data indicate that ablation of NHE3 severely impairs iron absorption and homeostasis in the mouse and suggest that the acidic microclimate drives DMT1‐mediated iron uptake at the intestinal brush border.Grant Funding Source: Supported by PHS Grant DK080047
Effect of calcium on amino acid and dipeptide transport by intestines of American lobster (Homarus americanus) and Atlantic white shrimp (Litopenaeus setiferus) (908.6)
Authors: Peterson Maria , Lane Amy , Ahearn Gregory 
Published: June 2021

Previous work using L‐histidine and zinc in American lobster intestine has shown these solutes can be transported as bis‐complexes (Histidine‐Zinc‐Histidine) across the intestine using a peptide transporter. Furthermore, transport of L‐leucine has been shown to be inhibited by high calcium concentrations. Dipeptide and bis‐complex transport and the role of calcium were investigated in the perfused intestine of lobster and Atlantic white shrimp. Samples of serosal medium were analyzed for amino acid composition by gas chromatography. In lobster, the transport of glycylsarcosine (Gly‐Sar) from mucosal to serosal medium was measured for a range of pH values and either 0.5mM or 25mM calcium chloride. The rate of Gly‐Sar transport was stimulated two‐fold with pH 8.5 in the lumen. Reduced calcium chloride concentration stimulated Gly‐Sar transport two‐fold. In shrimp, the transport of L‐histidine from mucosal to serosal medium was measured. The addition of 50µM zinc chloride increased the rate of histidine transport, while Gly‐Sar inhibited transport. The rate of histidine transport was significantly higher with 1mM calcium chloride than with 25mM. These results indicate that shrimp transport bis‐complexes in a manner similar to lobster, which is inhibited by the presence of a competing dipeptide. High calcium concentration has an inhibitory effect on both amino acid and dipeptide transport.Grant Funding Source: Supported by USDA Agricultural and Food Research Initiative Competitive Grant no. 2010‐65206‐20617
Programming effects of metformin exposure during gestation on offspring pancreatic β‐cell mass and glucose homeostasis (910.5)
Authors: Gregg Brigid , Alejandro Emilyn , Smith Michelle , Elghazi Lynda , El‐Gabri Deena , Cras‐Meneur Corentin , Bernal‐Mizrachi Ernesto 
Published: June 2021

Background: Epidemiologic studies have linked abnormal maternal nutrition to increased offspring susceptibility to type 2 diabetes (T2D). The developing pancreas is extremely sensitive to metabolic stressors, and exposure to energy or nutrient imbalances during gestation impacts its development leading to long‐term changes in β‐cell mass and function (β‐cell programming). How nutrients affect developing β‐cells to induce long‐lasting consequences is unclear, but signaling pathways that convey information about energy and nutrient status are prime candidates. The AMP‐activated protein kinase (AMPK) is a nutrient sensor that it is indirectly activated by metformin, the most widely used oral agent for T2D.Objective: To establish how metformin administration during pregnancy impacts β‐cell mass and susceptibility to diabetes later in life in a rodent model.Methods: Metformin was delivered in drinking water to c57bl/6 mice from embryonic day 0.5 (E0.5) and continued throughout gestation (Met group). Animals were examined during embryonic stages, at birth and as adults.Results: Pancreatic buds were examined at E14 by staining for markers of pancreatic and endocrine progenitor populations, Pancreatic and duodenal homeobox 1 (Pdx‐1) and neurogenin 3 (Ngn3) respectively. Met embryos had an increase in Ngn3 and Pdx‐1 number. The Met offspring did not differ from controls in terms of birth weight or length but had a lower random glucose. Met neonates were found to have increased β‐cell mass at birth when compared to controls. On examining offspring for adult metabolic phenotype, the Met animals displayed improved glucose tolerance and insulin secretion compared to controls.Conclusions: In utero exposure to metformin may have a positive impact on regulation of endocrine cell development. Metformin is currently in clinical trials for use in gestational diabetes. Thus, careful characterization of the effect of in utero exposure to metformin on offspring metabolic phenotype is essential.Grant Funding Source: Supported by DK‐084236‐03‐S1
Changes in diacron‐reactive oxygen metabolites and biological antioxidant potential in maternal serum during pregnancy (910.6)
Authors: Kawashiro Yukiko , Ishii Kuniko , Hosoyamada Yasue , Miyaso Hidenobu , Matsuno Yoshiharu , Kubonoya Kiyoshi , Mori Chisato , Hanazato Masamichi 
Published: June 2021

The objective of this research is to identify changes in serum oxidative stress and antioxidant levels during normal pregnancy using the diacron‐reactive oxygen metabolites (d‐ROMs) test and biological antioxidant potential (BAP) test. This cross‐sectional study enrolled 126 pregnant women who attended a maternity clinic in Japan. Healthy, non‐pregnant women of reproductive age were recruited as controls. Serum d‐ROMs and BAP were measured within 72 hours using a Free Radical Elective Evaluator. Subjects were divided into five groups: 8‐13 w (n=15), 14‐27 w (n=42), 28‐32 w (n=31), 36‐37 w (n=38), and control (n=7). The pregnant women’s average d‐ROMs and BAP levels were 499.4 ± 99.0 U.CARR and 1977.1 ± 179.3 μmol/l, respectively. The d‐ROMs level in 36‐37 w group increased significantly compared with the control, 8‐13 w and 14‐27 w groups (p=0.000, p=0.009, p=0.006). The BAP level in the 36‐37 w group decreased significantly compared with all other groups (p=0.000). These results suggest that oxidative stress increases and antioxidant power decreases throughout the gestational period, and that the pro‐oxidant antioxidant balance is disturbed most at the end of gestation.Grant Funding Source: KAKENHI（Grants‐in‐Aid for Scientific Research)
Maternal protein restriction during pregnancy alters vasodilator mechanisms in fetal placental arteries (910.9)
Authors: Sane Mukta , Lekatz Leslie , Shukla Praveen , Vonnahme Kimberly , O'Rourke Stephen 
Published: June 2021

Maternal undernutrition during pregnancy reduces uterine blood flow. We hypothesized that reduced maternal protein intake during pregnancy alters vasodilator responses in placental arteries. Pregnant ewes were fed an isocaloric diet containing 100% (control) or 60% (protein‐restricted) of protein requirements from day 100‐130 of gestation (term= 145 d). Fetal placental arteries (FPA) were isolated on day 130. Sensitivity to bradykinin (BK)‐induced relaxation was increased 5‐fold in FPA from protein‐restricted ewes. In control FPA, BK‐induced relaxation was unaffected by indomethacin (Indo) but was inhibited by nitro‐l‐arginine (NLA). In FPA from protein‐restricted ewes, neither Indo nor NLA affected the response to BK. Sodium nitroprusside‐induced relaxation, phenylephrine (PE)‐induced contraction, and expression of eNOS, guanylyl cyclase (GC), and BK‐receptors, was similar in FPA from both dietary groups. In ewes fed a control diet, BK‐induced relaxation of FPA is mediated primarily by NO. In ewes fed a protein‐restricted diet, FPA are more sensitive than controls to BK‐induced relaxation and the mechanism is independent of NO and PGI2. The altered BK response is not due to changes in sensitivity to NO or PE, or to altered expression of eNOS, GC or BK receptors and may represent an adaptive mechanism to ensure adequate blood supply to the fetus during adverse maternal dietary conditions.Grant Funding Source: Supported by NIH
Study of stress induced failure of the blood‐gas barrier and the epithelial‐epithelial cells connections of the lung of the domestic fowl, Gallus gallus variant domesticus after vascular perfusion (913.9)
Authors: Maina John , Jimoh Sikiru 
Published: June 2021

Complete blood‐gas barrier breaks (BGBBs) and epithelial‐epithelial cells connections breaks (E‐ECCBs) were counted in the lungs of free range chickens, Gallus gallus variant domesticus after vascular perfusion at different pressures. The E‐ECCBs exceeded the BGBBs by a factor of ~2. This showed that the former parts of the gas exchange tissue were structurally weaker or more susceptible to failure than the later. The differences in the numbers of BGBBs and E‐ECCBs in the different parts of the lung supplied with blood by the four main branches of the pulmonary artery (PA) corresponded with the diameters of the branches, the angles at which they branched from the PA, and the positions along the PA where they branched. Most of the BGBBs and the E‐ECCBs occurred in the regions supplied by the accessory‐ and the caudomedial branches: the former is the narrowest branch and the first blood vessel to separate from the PA while the latter is the most direct extension of the PA and is the widest. The E‐ECCBs appeared to separate and then fail from tension in the blood capillary walls as the perfusion‐ and the intramural pressures increased. Compared to the mammalian lungs on which data are available, i.e., those of the rabbit, the dog, and the horse, the BGB of the lung of free range chickens is substantially stronger for its thinness.Grant Funding Source: Supported by The national Research Foundation of South Africa
The effect of AFO stiffness on the knee joint during the heel strike phase of gait in stroke patients (919.12)
Authors: Singer Madeline , Kobayahi Toshiki , Lincoln Lucas , Orendurff Michael , Foreman K. Bo 
Published: June 2021

Stroke patients suffering from foot drop are often prescribed ankle‐foot orthoses (AFOs) to improve foot clearance during gait. However, excessive restriction of plantarflexion (PF) during the heel strike phase of gait has been shown to cause biomechanical changes at the knee joint. This pilot study aimed to determine how increasing the PF stiffness of an AFO affects knee joint kinematics and kinetics during heel strike in hemiplegic stroke patients with varying levels of active ankle range of motion. We hypothesized that increased PF resistance would cause an increase in anterior tibial rotation at heel strike with resulting increases in knee flexion angle and knee extension moment. To test this hypothesis, 5 stroke patients with foot drop were clinically evaluated, instrumented with reflective markers, and fitted with a spring modified AFO (Orthocare Innovations). A compression spring in the posterior aspect of the AFO was changed to increase the external dorsiflexion torque from 0.3 Nm/deg (Spring 1) to 2.0 Nm/deg (Spring 2). Kinematic and kinetic data were collected during walking on an instrumented treadmill (Bertec) in a motion analysis lab. Five steps with each spring were examined. Two patients exhibited an increase in knee flexion angle and knee extension moment with the stiffer spring. Clinical findings revealed that these 2 patients had minimal active PF while the other 3 patients had full active PF. From these initial results, we cautiously conclude that stroke patients with decreased active PF cannot overcome excessive PF resistance during the heel strike phase of gait, and as a result exhibit compensation strategies at the knee joint. These results will be used to create a more objective method for the prescription of AFOs in hopes to improve the long‐term quality of life for stroke patients.Grant Funding Source: Supported by National Institutes of Health (2R44HD069095‐02)