bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nutritional status of paediatric cancer patients from the UK: a prospective cohort study (825.7)
Authors: Revuelta Iniesta Raquel , Jane McKenzie , Ilenia Paciarotti , Mark Brougham , David Wilson 
Published: June 2021

Aim: To investigate the prevalence of malnutrition, patterns of change in nutritional status (NS) and potential factors which may contribute to the development of malnutrition in newly diagnosed Scottish paediatric cancer patients.Methods: NS was assessed between Aug 2010‐Oct 2013 using anthropometry, body composition and dietary assessment. The primary outcome was malnutrition defined as body mass index (BMI) according to UK guidelines. Frisancho’s (1981) reference was used for arm anthropometry and to estimate muscle (FFM) and fat mass (FM). Correlations and multilevel analysis were performed.Results: 74 (78%) patients were recruited. At baseline, the prevalence of undernutrition was 9.5%, overnutrition 5% and obesity 11%. Triceps skinfold identified the highest prevalence of undernutrition 13.5% and the lowest of obesity 1%. BMI [p=0.03; 95% CI (‐17 to ‐12)] and FM [p<0.05; 95% CI (677‐1122)] significantly increased after 3 months and remained steady thereafter, whilst FFM [p<0.001; 95% CI (2992‐3550)] significantly decreased during the first year. Only energy intake showed minor correlation with BMI (r=0.1; p=0.04) and TSF (r=0.2; p=0.03) at baseline.Conclusion: Undernutrition was more prevalent at diagnosis, yet overnutrition increased significantly during treatment. The changes seen in body composition emphasise the need to implement new strategies to improve the NS of paediatric cancer patients. Grant Funding Source: Fergus maclay Leukaemia Trust, Queen Margaret University and Leukaemia and Cancer Research Fund
Potential of a defatted green microalgal biomass as an iron source for hemoglobin repletion (828.8)
Authors: Kim Jonggun , Lei Xin Gen 
Published: June 2021

Iron deficiency anemia is a widespread nutritional disorder around the world, and pigs are an excellent model to study human iron nutrition. Previous research in our laboratory demonstrated a tendency of feeding iron‐rich microalgae to elevate blood hemoglobin concentrations in pigs fed iron‐adequate diets. Two experiments were conducted in weanling pigs to determine such effectiveness of a defatted green microalgal biomass (Desmodesmus sp., Cellana, Kailua‐Kona, HI) generated from the biofuel research. In Experiment 1, pigs (11.3 ± 0.6 kg of body weight) with low hemoglobin concentrations (8.2 ± 2.9 g/dL) were fed a corn‐soy basal diet (BD) without supplemental iron (n = 5) or the diet plus 7.5% microalgae (n = 6) for 5 wk. The algae diet elevated (P < 0.05) packed cell volume by 23‐26% and blood hemoglobin concentrations by 22‐32% at or after wk 3. In Experiment 2, pigs (12.9 ± 0.6 kg) with normal blood hemoglobin concentrations (12.1 ± 0.38 g/dL) were fed the BD supplemented with ferrous sulfate (n = 10) or 15% algae (n = 10) for 5 wk. There was no dietary treatment effect on either packed cell volume or hemoglobin concentrations. The diets did not alter body weight gain or daily feed intake of pigs in either experiment. In conclusion, the defatted green microalgal biomass was effective in helping hemoglobin repletion of marginally anemic pigs. Our ongoing research is exploring novel promoting mechanisms of the biomass in addition to its high iron concentration.Grant Funding Source: Supported in part by a USDA/DOE Biomass R&D Initiative grant (2010‐0106)
Dose response of aged garlic extract in streptozotocin ‐induced diabetic rats (829.9)
Authors: Thomson Martha , Al‐Qattan Khaled , J.S. Divya , Ali Muslim 
Published: June 2021

The anti‐diabetic and antioxidant effects of 3 doses of aged garlic extract (AGE) were studied in diabetic rats. Diabetes was induced by IP injection of streptozotocin (STZ) and a fasting blood sugar >300 mg/dl indicated diabetes. AGE (Wakunaga‐Kyolic, USA) was administered at 3 different doses intraperitoneally (IP) – 600, 300 and 100 mg/kg ‐ daily for 8 weeks. Diabetic rats were divided into 5 groups; control, boiled AGE‐treated and the 3 AGE‐treated groups. A normal control group was also included. Effects in AGE‐treated diabetic rats were dose dependent. STZ‐induced diabetic rats lost significant weight during the experiment with AGE‐treated rats (600 and 300 mg/kg doses) maintaining their initial weights. Blood glucose as well as serum cholesterol and triglycerides were significantly elevated in diabetic rats, and lowered by AGE treatment. Serum insulin level was decreased over 10‐fold in diabetic rats and increased by AGE treatment; while erythrocyte glycated hemoglobin (GHb) increased over 3‐fold in diabetic rats with a marked decrease in AGE‐treated diabetic rats. Total antioxidant levels and catalase activity decreased (45‐70%) in serum, kidneys and livers of diabetic rats with significant recovery in AGE‐treated animals. In contrast, lipid peroxidation (MDA levels) increased in kidneys and livers of diabetic rats and was lowered in AGE‐treated diabetic rats. In general, administration of boiled AGE had few beneficial effects compared to AGE. Thus, AGE exhibits a dose‐dependent effect in ameliorating oxidative stress and other indicators of diabetes in STZ‐induced diabetic rats. The study was supported by KU grant #SL 02/13.Grant Funding Source: Supported by Kuwait University SL 02/13
Chondroprotective role of whole grape polyphenols in stimulated SW 1353 cells (830.27)
Authors: Lucero Jacquelynn , Vijayagopal Parakat , Juma Shanil 
Published: June 2021

In aging, increases in oxidative stress and inflammation cause an imbalance in the metabolic activity of chondrocytes leading to onset and progression of osteoarthritis. Resveratrol, a polyphenol rich in grapes has shown to inhibit chondrocyte apoptosis and suppress cyclooxygenase (COX‐2). Our study investigated the effect of whole grape polyphenols on cartilage cell integrity and markers of cartilage health using SW 1353 human chondrosarcoma cells that are compatible to primary chondrocytes. Whole grape polyphenols (WGP) were extracted from grape powder and concentrations were determined using Folin‐Calteau assay. For all experiments, cells treated with WGP were stimulated with the inflammatory compound, tert‐butyl hydroperoxide (tbHP). Cell proliferation significantly (p<.05) increased in a dose dependent manner with WGP at 20ug/ml (147% vs. Control). Cartilage degradation as indicated by glycoprotein‐39 (YKL‐40) levels was significantly lower with the three highest doses of WGP in comparison to control and tbHP stimulated cells. Toluidine blue and Safarin O staining indicated increase presence of type II collagen and proteoglycan in WGP treated cells. Using In‐Cell colorimetric ELISA, we did not observe a significant effect on COX‐2 protein expression with any WGP doses. Elucidation of mechanisms by which WGP protect cartilage cell destruction in presence of an inflammatory agent are warranted.Grant Funding Source: Supported by California Table Grape Commission
Pulmonary expression and regulation of Cldn6 by tobacco smoke (834.3)
Authors: Jimenez Felix , Lewis Josh , Belgique Samuel , Wood Tyler , Reynolds Paul 
Published: June 2021

Smoking is a major risk factor for several chronic diseases including chronic obstructive pulmonary disease (COPD), a condition involving both emphysema and inflammation of the airways. COPD severity directly relates to abnormalities of pulmonary epithelial cells. Claudins contribute to tight junctions that prevent paracellular transport of extracellular fluid and diverse substances and Claudin 6 (Cldn6) is a protein expressed prominently in the lung parenchyma. To determine whether Cldn6 was differentially influenced by tobacco smoke, Cldn6 was evaluated by q‐PCR, immunoblitting, and immunofluorescence following exposure to tobacco smoke. Q‐PCR and immunoblotting revealed that Cldn6 was increased in alveolar type II‐like epithelial cells (A549) but not in Bease2B cells, a cell line derived from proximal airway epithelium. Luciferase assays incorporating 0.5kb, 1.0kb, or 2.0kb of the Cldn6 promoter also revealed increased transcription of the gene when cells were exposed to cigarette smoke extract. Cldn6 was also markedly increased in the lungs of Balb/C mice exposed to tobacco smoke delivered by an automated smoke machine (InExpose, Scireq, Canada) compared to animals exposed to room air. These data reveal for the first time that tight junctional proteins are differentially regulated by tobacco smoke exposure and that Cldns are potentially involved as neighboring epithelial cells respond to tobacco smoke. Further research may show that complexes between cells contribute to impaired structural integrity of the lung coincident with smoking.Grant Funding Source: Supported by the Flight Attendant’s Medical Research Institute (FAMRI) and a BYU MEG Award (PRR).
Renal endoplasmic reticulum stress is induced via endothelin A receptor activation (857.7)
Authors: De Miguel Carmen , Hobbs Janet , Pollock David , Pollock Jennifer 
Published: June 2021

The endothelin (ET‐1) system has been recently implicated in renal endoplasmic reticulum (ER) stress development, a type of cellular stress caused by misfolded protein accumulation within this organelle. To clarify the role of the ETA receptor in renal ER stress, we hypothesized that pharmacological blockade of this receptor via ABT‐627 leads to reduced renal response to the ER stress inducer tunicamycin (TM). WT and ETB deficient (sl/sl) rats (n=3‐4/group) were pre‐treated with ABT‐627 (5mg/kg/day; drinking water) for 1 week and given a single injection of TM (2ug/g bwt; i.p.). Kidneys, plasma and urine were collected 24h later. ER stress markers in renal cortical and medullary regions were determined by qRT‐PCR. Treatment of WT animals with ABT‐627 significantly reduced the ER stress response to TM in cortex and outer medulla (fold change/WT+H2O; GRP78 (0.12±0.02 and 0.04± 0.01, respectively), ATF‐4 (0.20± 0.02 and 0.15± 0.02), ATF‐6 (0.28± 0.08 and 0.18± 0.04), spliced XBP‐1 (0.03+0.01 and 0.05± 0.01) and CHOP (0.02± 0.01 and 0.04± 0.01). On the contrary, ABT‐627 pre‐treatment failed to decrease cortical and medullary ER stress development in sl/sl rats. These results indicate that ETA receptor activation leads to induction of renal ER stress genes, while ETB receptor activation has protective effects. Modulation of the ET system may have therapeutic value in protecting against ER stress‐induced renal injury.Grant Funding Source: Supported by NIH and AHA
Relationship between muscle stiffness and strength in older adults: implications for the development of sarcopenia (863.2)
Authors: Hibbert Jamie , Domire Zachary 
Published: June 2021

Introduction: It has been shown that older adults have an attenuated hypertrophic response to exercise as compared to young adults. One possible explanation for this response is decreased mechanotransduction into the myocytes due to stiffening of the extracellular matrix with the aging process; thus muscle cells will experience less strain and therefore less mechanical signaling for any applied force. We hypothesize that muscle stiffness decreases response to exercise, and that there is an inverse relationship between strength and muscle stiffness. This would indicate that muscle stiffening plays a role in the development of sarcopenia.Objective: The purpose of this study is to determine the relationship between muscle stiffness and strength in older adults.Methods: Data on muscle stiffness and strength were collected for 19 healthy women (age 70‐80). Stiffness measurements were taken of the Vastus Lateralis using ultrasound elastography (SuperSonic Imagine). Maximal strength was measured using a HUMAC isokinetic dynamometer.Results: Two subjects were excluded for lack of effort during strength testing. There was a moderate correlation (r=‐0.36) between strength and muscle stiffness. There was no relationship (r=‐0.2) between strength and age.Conclusions: This supports the hypothesis that muscle stiffness contributes to decreased response to exercise and the development of sarcopenia.
Endochondral bone tissue engineering: using cartilage to drive vascularized bone regeneration (87.6)
Authors: Bahney Chelsea , Jha Amit , Hu Diane , Taylor Aaron , Britz Hayley , Hallgrimsson Benedikt , Miclau Ted , Marcucio Ralph 
Published: June 2021

There is a significant unmet clinical need to develop improved strategies to promote vascularized bone regeneration. Current bone graft technologies promote repair through direct osteogenesis by use of auto‐ or allografted bone. Critical failures associated with these therapies include osteonecrosis and poor osseointegration. The long‐term goal of this project is to develop a tissue engineering approach to promote endochondral bone formation, in which bone forms through a cartilage intermediate. Endochondral ossification is the normal mechanism by which long bones form and the majority of fractures heal. By leveraging this normal healing response, we hypothesize we can overcome the clinical problems of osteonecrosis and poor integration to produce a vascularized and integrated bone regenerate. To test this hypothesis, critical sized defects were created in mid‐diaphysis of murine tibia. Defects remained empty, or were filled with a cartilage graft, autograft or allograft bone. Our data show cartilage grafts effectively transformed into vascularized bone and integrated with the host bone to perform statistically better than allografts and equivalent to autografts. To translate this therapy we have developed a biomimetic acrylated hyaluronic acid hydrogel that contains peptide sequences for cell attachment (bone sialoprotein‐derived RGD), heparin for modulation and sequestration of growth factors, and enzymatically degradable MMP‐13 crosslinks. Hypertrophic chondrocytes encapsulated in these scaffolds mineralization during in vitro culture in basal medium. In ongoing work, these scaffolds have been transplanted into a subcutaneous model of osteonecrosis to evaluate the capacity to re‐vitalize bone. This novel approach to bone tissue engineering has the potential to improve clinical outcomes in bone regeneration.Grant Funding Source: Supported by NIH 5F32AR062469 (CSB), MTF Junior Investigator Award (CSB), UCSF CTSI Award (CSB)
Intrathecal BDNF acutely enhances rhythmic phrenic activity after cervical spinal cord injury in rats (871.3)
Authors: Mantilla Carlos , Zhan Wen‐Zhi , Ermilov Leonid , Sieck Gary 
Published: June 2021

Upper cervical spinal cord injury (SCI) disrupts descending inspiratory‐related drive to phrenic motoneurons paralyzing the diaphragm muscle. Over time following unilateral C2 hemisection (SH), there is gradual recovery of rhythmic diaphragm activity ipsilaterally, consistent with neuroplasticity. We recently reported that functional recovery after SH is enhanced by chronic intrathecal delivery of BDNF to the region of the phrenic motor neuron pool. BDNF also exerts acute effects on synaptic transmission that may enhance functional recovery. Accordingly, we hypothesized that intrathecal delivery of BDNF to the phrenic motor neuron pool acutely enhances functional recovery post‐SH. Rats were implanted with diaphragm electrodes for chronic EMG recordings post‐SH, verifying absence of ipsilateral eupneic diaphragm EMG activity by 3 and 28 days after SH. In spontaneously breathing, anesthetized animals, BDNF was administered intrathecally (30 μl) at C4 and ipsilateral rhythmic diaphragm EMG activity was restored (~120% of pre‐injury diaphragm root‐mean‐square [RMS] EMG amplitude) within ~30 min of administration. Diaphragm RMS EMG increased further following exposure to hypoxia (10% O2)‐hypercapnia (5% CO2) and intranasal capsaicin. These results highlight the acute role of BDNF signaling in the phrenic motor neuron pool in chronically‐injured rats displaying no spontaneous recovery.Grant Funding Source: Supported by NIH grant R01 HL096750.
Angiotensin‐II promotes ACE2 shedding by increasing ADAM17 expression and oxidative stress in Neuro2A cells (874.10)
Authors: Moreira de Queiroz Thyago , Sriramula Srinivas , Chaudhari Anju , Filipeanu Catalin , Lazartigues Eric 
Published: June 2021

Decrease of Angiotensin‐converting enzyme 2 (ACE2) expression and activity in the brain has been shown to be associated with neurogenic hypertension. We recently reported that up‐regulation of the matrix metalloprotease A Disintegrin And Metalloprotease 17 (ADAM17) expression in hypertension mediates ACE2 shedding in neurons. To study the contribution of Ang II Type 1 Receptor (AT1R) and oxidative stress on ACE2 shedding, Neuro2A (neuronal cell line) were first transfected with human ACE2 (hACE2) then pretreated with AT1R blocker Losartan (10 µM) or the reactive oxygen species scavenger Tempol (10 µM), 30 min prior to treatment with AngII (100 and 300 nM). Western blotting revealed that ACE2 expression was decreased (12 and 40%, respectively), while ADAM17 expression was increased (30 and 36%, respectively) in Neuro2A cells after Ang II treatment. Pretreatment with losartan or tempol attenuated the effect of Ang II on ADAM17 expression (18 and 19%, respectively). To further study the involvement of oxidative stress in Ang II‐induced ADAM17 expression, another set of Neuro2A cells were studied without transfection with hACE2. In these cells treated with Ang II (100 nM), ADAM17 expression was similarly decreased by tempol. These data suggest that ADAM17 expression is increased by an AT1R‐dependent, as well as oxidative stress‐dependent mechanism, leading to enhanced ACE2 shedding in neurons.Grant Funding Source: Supported by AHA 12EIA8030004, CNPq
Rostrocaudal changes in the protein expression of NMDA receptor subunits within the rostral ventrolateral medulla of sedentary and active rats (875.12)
Authors: Subramanian Madhan , Mueller Patrick 
Published: June 2021

Recently we found enhanced sympathoexcitatory responses to glutamate in the RVLM following sedentary conditions. We have also reported increased dendritic branching in more rostral compared to caudal regions within the RVLM of sedentary rats. The mechanisms by which physical inactivity increases glutamatergic neurotransmission and produces structural changes in more rostral regions of the RVLM is unclear. The NMDA subtype of glutamate receptor has been associated with neuroplasticity in other brain regions of sedentary versus active rats. We hypothesized that sedentary conditions would alter protein expression of NMDA receptor subunits in a rostrocaudal manner within the RVLM. To test this hypothesis, male Sprague Dawley rats were allowed to remain sedentary (n=4) or exercise voluntarily via running wheels (n=4) for 14 weeks. Animals were then sacrificed and the RVLM cryosectioned (80 μm) and micropunched bilaterally. Sections were stained using cresyl violet to identify the rostrocaudal boundary of the RVLM. Based on their location relative to the caudal pole of the facial nucleus (FN), punches were pooled into four regions: caudal ‐480 µm (FN‐480), caudal ‐240 µm (FN‐240), rostral +240 µm (FN+240) and rostral +480 µm (FN+480). Preliminary western blot results showed that within the RVLM of sedentary rats, NR1 protein expression normalized to actin was significantly higher at FN‐480 (2.6 ± 0.2) compared to FN+240 (1.6 ± 0.2, p < 0.005). Interestingly, within the caudal regions of the active rats, NR1 protein expression was significantly lower at FN‐480 (1.4 ± 0.2) compared to FN‐240 (2.3 ± 0.2, p < 0.005). Changes were not observed for NR2A protein expression within both groups. Rostrocaudal differences observed in sedentary rats were not consistent with our structural findings. However, it is important to further investigate these novel findings, including examination of other receptor subunits which could relate to the structural neuroplasticity observed in sedentary rats.Grant Funding Source: R01HL096787
17β‐Estradiol replacement to ovariectomized rats ameliorates depression‐like behavior (876.2)
Authors: Lu Jiangqiang , Xu Yongjun , Sheng Hui , Tang Zhiping , Ni Xin 
Published: June 2021

Administration of estrogens elicits antidepressant‐like effects in female rats. However, the mechanism of this effect remains largely unknown. Inflammation and indoleamine‐2,3‐dioxygenase (IDO) have been implicated to play pivotal roles in the depression‐like behavior. The objective of the present study was to investigate whether estrogen deficiency‐induced depression‐like behavior is associated with inflammation and IDO activation in brain. It has been found that ovariectomy induced depression‐like behaviors in rats, while 17β‐estradiol (E2) treatment for 12‐week ameliorated depression‐like behaviors in ovariectomized (OVX) rats. Ovariectomy resulted in a decrease in 5‐HT and BDNF levels and an increase in levels of IDO, proinflammatory cytokines IFN‐γ and IL‐6, TLR‐4 and phosphorylated NF‐κB (p65 subunit) in hippocampus but not in prefrontal cortex. These effects could be restored by E2‐replacement. Serum E2 level was inversely correlated with the levels of IDO, IFN‐γ and IL‐6, while positively correlated with 5‐HT in hippocampus. Our results suggested that estrogen inhibit inflammation and activation of IDO and maintains 5‐HT and BDNF level in hippocampus, thereby ameliorating depression‐like behavior.Grant Funding Source: Natural Science Fundation of China No.31371197
Blood oxygen content and affinity in developing embryos of snapping turtle Chelydra serpentina (879.8)
Authors: Sartori Marina , Kohl Zachary , Taylor Edwin , Abe Augusto , Crossley Dane 
Published: June 2021

In egg‐laying amniotic vertebrates gas exchange takes place over the chorioallantoic membrane (CAM). Oxygen diffuses from air in contact with the shell into blood perfusing the membrane where it combines reversibly with hemoglobin. The capacity of the blood to transport oxygen is determined by the functional characteristics of the hemoglobin. In this study we investigated changes in oxygen content and affinity during development in embryos of snapping turtle (Chelydra serpentina). Blood samples were taken from embryos at 50, 70 and 90% of incubation. Samples withdrawn from the CAM artery had statistically similar mean oxygen contents for all stages (combined mean ± SEM; 0.94 ± 0.13 mL O2/100 mL of blood). Mean CAM venous blood oxygen content was 2.74 ± 0.44 at 50%, 3.25 ± 0.26 at 70% and increased to 4.97 ± 0.47 mL O2/100 mL at 90% of development. Consequently, the arteriovenous difference increased by 72% late in incubation. Oxygen equilibrium curves were the same at 2% and 6% CO2 at 50% incubation but showed an increased affinity in 2% CO2 and a rightward shift in 6% CO2 at 70 and 90% of development. These results show that embryonic turtles increase oxygen content and affinity and show a Bohr shift late in development likely favoring hemoglobin loading at the CAM and unloading at the tissues, ensuring adequate O2 supply for the increased demand of later stages of development.Grant Funding Source: Supported by NSF CAREER IBN IOS‐0845741 (DAC) and FAPESP 2012/06938‐8 (EWT); 2013/05677‐9 (MRS)