bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lipin Expression Correlates to Differences in Phospholipid Profiles in Drug‐Resistant Prostate Cancer Cells
Authors: Finnerty Morgan C. , Cummings Brian S. 
Published: May 2022

PURPOSEThe association between clinical outcomes of prostate cancer progression and lipid remodeling is not well understood. Although it is known that increases in select circulating lipids correlate to decreased patient survival, the mechanisms mediating alterations in these lipids are not fully explained. We addressed this gap‐in‐knowledge using in vitro models of non‐cancerous, hormone‐sensitive, castration‐resistant prostate cancer (CRPC), and docetaxel resistant (DR) CRPC cell lines combined with quantitative HPLC‐ESI‐Orbitrap‐MS lipidomic analysis.HYPOTHESISWe hypothesized that the expression of lipin (phosphatidic acid phosphatase), an enzyme mediating the conversion of phosphatidic acid to diacylglycerol, correlates to changes in lipidomic profiles in prostate cancer cells. We further hypothesized that the lipidomic profile of metastatic CRPC cell lines (PC‐3 and DU‐145) will shift as they are undergoing multiple treatments of docetaxel.METHODSLipids were isolated using the Bligh‐Dyer extraction from non‐cancerous, hormone‐sensitive, CRPC, and DR‐CRPC cell lines. Lipids were initially analyzed using an untargeted shotgun approach (ESI‐MS), followed by a targeted‐based quantitative HPLC‐ESI‐Orbitrap‐MS approach. Post data acquisition were based on multiple methods including isotope, carbon number (to internal standards) and ionization efficiency‐based corrections. Online resources and software's utilized included MetaboAnalyst, LIPIDMATCH, LIPID MAPS, XCMS, and MZmine.Lipin‐1 expression in cells was determined using immunoblot analysis. Docetaxel‐sensitive traits were obtained after five treatments of 1 nM docetaxel between passages of the CRPC cell line PC‐3. Results were demonstrated by a 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐Diphenyltetrazolium Bromide (MTT) assay.RESULTSOur data showed significant changes in the abundance of lipid species between the various cell lines and a correlation between select lipid species and the progression of prostate cancer. Prominent among these were the levels of phosphatidic acid (PA) and diacylglycerol (DAG). Most notably, PA levels in cells tended to inversely correlate with DAG levels. These levels correlated to the decreased expression on lipin, specifically lipin‐1.CONCLUSIONSDistinct phospholipid classes were observed to have increased levels in prostate cancer cells, as compared to non‐cancer cells. The protein expression of lipin‐1 in most prostate cell lines correlated to the abundance of PA, excluding the DR cell lines. This suggests that altered lipin expression correlates to decreased survival. Additionally, dosing the parent and treated PC‐3 cells with a range of docetaxel indicated that the 5x1nM treated cells had a larger cytotoxic effect to docetaxel, as compared to the non‐treated cells.REFERENCESIngram, L.M., et al., Identification of lipidomic profiles associated with drug‐resistant prostate cancer cells. Lipids Health Dis, 2021. 20(1): p. 15.
Effects of Beta‐Blockers on Thermal and Cardiovascular Strain of Adults With Coronary Artery Disease During Extreme Heat Events
Authors: Chaseling Georgia , Batlett Audrey‐Ann , Capon Anthony , Crandall Craig , Fiatarone Singh Maria , Bi Peng , Nigam Anil , Jay Ollie , Gagnon Daniel 
Published: May 2022

IntroductionExtreme heat is associated with a greater risk of adverse cardiovascular events, especially in people with cardiovascular disease. Many patients with cardiovascular disease are prescribed beta‐blockers. Some research suggests that in young healthy adults, cardio‐selective beta‐blockers may alter heat loss capacity. However, the effects of beta‐blockers on temperature regulation in older adults during an extreme heat event are unknown. The objective of this study was to compare thermal and cardiovascular responses during simulated extreme heat events between older adults with coronary artery disease (CAD) who use and do not use beta‐blockers. It was hypothesised that the increase in heart rate and skin blood flow would be smaller in CAD patients who use beta‐blockers compared to those who do not use beta‐blockers.Method25 older adults (23 males/2 females) with stable CAD, 18 taking cardio‐selective beta‐blockers (BB: 66±8 y; 85.7±13.3 kg; 28.0±4.6 kg/m2) and 7 not taking beta‐blockers (NBB: 66±7 y; 77.1±14.6 kg; 26.1±3.9 kg/m2), were exposed to two 3‐hour simulated extreme heat events; one hot and humid (38°C, 60% relative humidity) and one hot and dry (45°C, 10% relative humidity). Rectal and mean skin temperatures, heart rate, and skin blood flow were continuously recorded. Whole body sweat losses were calculated from changes in nude body weight.ResultsAt the end of the 3‐h hot and humid heat exposure, relative to pre‐exposure baseline the change in heart rate (BB: +7±5 bpm; NBB: +11±9 bpm, p=0.20), rectal (BB: +0.57±0.27°C; NBB: +0.60±0.31°C, p=0.76) and mean skin (BB: +5.1±1.2°C; NBB: +5.1±1.1°C, P=0.91) temperatures, and whole body sweat losses (BB: 771±480 g; NBB: 798±172 g, p=0.88) did not differ between groups. The change in skin blood flow from baseline was greater in the NBB (+32±23 arbitrary units) compared to the BB (+9±7 arbitrary units; p=0.01) group. At the end of the 3‐h hot and dry heat exposure, the increase in heart rate (BB: +9±8 bpm; NBB: +9±5 bpm, p=0.93), rectal (BB: +0.61±0.40°C; NBB: +0.62±0.22°C, p=0.91) and mean skin (BB: +5.9±0.9°C; NBB: +5.7±1.3°C; p=0.79) temperatures, whole body sweat losses (BB: 1252±174 g; NBB: 1207±169, p=0.56) and skin blood flow (BB: +26±22 arbitrary units; NBB: +26±39 arbitrary units; p=0.98) from baseline did not differ between groups.ConclusionOur preliminary evidence indicates that cardio‐selective beta‐blocker use does not alter thermal or cardiovascular strain in adults with stable coronary artery disease during simulated hot and humid or hot and dry extreme heat events.
SUN11602, a novel bFGF mimetic, exerts neuroprotective effects in Parkinson's disease
Authors: Casili Giovanna , Ardizzone Alessio , Bova Valentina , Campolo Michela , Lanza Marika , Filippone Alessia , Paterniti Irene , Esposito Emanuela 
Published: May 2022

Parkinson's disease (PD) is the second most frequent neurodegenerative disease, with a large prevalence in industrialized countries. The etiopathogenesis of PD is multifactorial and not yet fully known, however, in the last few decades, scientific world advised the establishment of a neuroinflammatory state among the possible risk factors. In this field, basic fibroblast growth factor/fibroblast growth factor receptor 1 (bFGF/FGFR1) could be a promising way to treat CNS‐mediated inflammation; however, the use of bFGF as a therapeutic agent is limited by its side effects.The novel synthetic compound SUN11602 exhibited neuroprotective activities like bFGF, but demonstrating greater safety, thus constituting a potential candidate for the treatment of neurodegenerative diseases including PD. In this perspective, this study aimed to evaluate the effect of SUN11602 administration in a murine model of MPTP‐induced PD. PD was induced by intraperitoneal injection of MPTP (80 mg/kg). SUN11602 (1, 2.5, and 5 mg/kg) was administered daily by oral gavage starting from 24 hours after the first administration of MPTP, mice were sacrificed 7 days after MPTP induction. The results obtained showed that SUN11602 administration significantly reduced the alteration of PD hallmarks, attenuating the neuroinflammatory state via modulation of glial activation, NF‐kB pathway and cytokine overexpression. Furthermore, we demonstrated that SUN11602 treatment rebalanced Ca2+ overload in neurons by regulating Ca2+‐binding proteins, inhibiting the apoptotic cascade. Therefore, considering these findings, SUN11602 could be considered a valuable pharmacological strategy for PD.
How does S‐palmitoylation affect the Organic Anion Transporting Polypeptide 1B1 (OATP1B1)?
Authors: Villanueva Cecilia E. , Hagenbuch Bruno 
Published: May 2022

BackgroundOrganic Anion Transporting Polypeptide 1B1 (OATP1B1) is an important transporter localized to the basolateral membrane of human hepatocytes that mediates the uptake of numerous therapeutics like statins, antibiotics, and anti‐cancer agents. Previous studies from our lab suggest that OATP1B1 is localized in membrane microdomains, also known as lipid rafts, which contain various components like saturated lipids, cholesterol, and lipidated proteins. Lipidated proteins are frequently the result of S‐palmitoylation, a reversible post translational modification that adds palmitic acid (C16:0) to cysteine residues. Currently, not much is known about the potential impact of S‐palmitoylation on OATP1B1 function and localization. Aim: We hypothesize that OATP1B1 is S‐palmitoylated and that this affects its function and localization.MethodsWe measured uptake of the model substrate estradiol‐17β‐glucuronide in cells expressing OATP1B1. S‐palmitoylation was detected using an acyl‐biotin exchange (ABE) assay in combination with western blotting. To prevent S‐palmitoylation, cells were preincubated with 2‐bromopalmitate (2BP). Expression of OATP1B1 at the plasma membrane was assessed using surface biotinylation.ResultsThe ABE assay demonstrated that OATP1B1 is S‐palmitoylated and that pretreatment of the cells for 18 hours with 2BP reduces S‐palmitoylation. Inhibition of S‐palmitoylation with 2BP for 18 hours also resulted in decreased OATP1B1‐mediated transport of estradiol‐17β‐glucuronide as well as in a reduction of surface expression of OATP1B1.Summary and ConclusionsOur results demonstrate that OATP1B1 is S‐palmitoylated. Inhibition of S‐palmitoylation reduces the function and the surface expression of OATP1B1. Thus, these findings suggest that S‐palmitoylation is a post‐translational modification involved in the regulation of this important hepatic drug uptake transporter.
Fibroblast Growth Factors are Associated with Parenchymal Hemorrhagic Infarction Following ELVO
Authors: Sands Madison , Ihsan Fizra , Frank Jacqueline , McLouth Chris , Maglinger Benton , Trout Amanda , Turchan Jadwiga , Stowe Ann , Fraser Justin , Pennypacker Keith 
Published: May 2022

ObjectiveThe goal of this study was to analyze possible associations between fibroblast growth factors (FGFs) and hemorrhagic conversion (HC) in patients with acute ischemic stroke that underwent mechanical thrombectomy (MT).BackgroundEmergent Large Vessel Occlusion (ELVO), often treated with MT, can lead to further complications such as HC. Little is known about predicting the risk and extent of HC. FGF‐21 and 23 are angiogenic proteins of the endocrine subfamily and are independent factors for overall risk of stroke and intracranial hemorrhage (PMID: 33967812). Comorbidities such as diabetes, obesity, hypertension, and hypercholesterolemia are also known to increase risk of HC and affect FGF levels.MethodsThe Center for Advanced Translational Stroke Science at the University of Kentucky utilizes the Blood and Clot Thrombectomy Registry and Collaboration (BACTRAC) protocol (www.clinicaltrials.gov NCT03153683) for collection of systemic (i.e. proximal to thrombus) arterial blood during a MT procedure. Blood samples collected from 61 patients were sent to Olink Proteomics for proteomic analysis. The European Cooperative Acute Stroke Study (ECASS II) grading system was used to differentiate between the types of HT: Hemorrhagic Infarction (HI 1 and 2) and Parenchymal Hemorrhagic Infarction (PH 1 and 2). Logistic regressions were used to determine the association of FGF with the subtypes of hemorrhagic conversion. Data analyses were performed using IBM SPSS Statistics.ResultsFGF‐21 and FGF‐23 were significantly higher in patients with HI versus PH‐type HC (p=0.043 and p=0.004 respectively). Logistic regression yielded a significant model for only FGF‐21 (χ2= 5.196, p=0.023). Increasing levels of FGF‐21 were associated with a decreased likelihood of having PH‐type HC. Most patients receiving TPA had decreased levels of FGF‐21 (p=0.04). Various comorbidities were tested but were not found to be significant.DiscussionThe data provides an indication that lower levels of FGF‐21 increase the odds for a worse type of hemorrhagic transformation. Lower levels of FGF‐21 are reported in patients with hypercholesterolemia and hypertension. Our study found TPA correlated with lower levels of FGF‐21. Taken together, patients with comorbidities that decrease FGF‐21 levels, such as hypertension and hypercholesterolemia, and those who receive TPA should be monitored more carefully following thrombectomy. FGF‐21 should be evaluated further as a potential biomarker for hemorrhagic transformation to administer adjunctive therapies to MT.
Sex Differences in Vascular Endothelial Function After Liver Transplant
Authors: Chavez Domenico A. , Bohmke Natalie J. , Martin Linsey , Miller Austin , Bhati Chandra , Wolver Susan , Siddiqui Mohammad S. , Kirkman Danielle L. 
Published: May 2022

INTRODUCTIONLiver transplant (LT) recipients have an increased risk of developing cardiovascular disease (CVD) after transplant. Sex differences may be a significant determinant in the pathophysiology of CVD. However, sex‐differences in vascular dysfunction, an established precursor to CVD, have not been explored in LT recipients. The purpose of this study was to investigate the sex differences in vascular function and cardiometabolic risk‐factors to CVD among LT patients.METHODSConduit artery endothelial function was measured via flow‐mediated dilation of the brachial artery (FMDBA) with duplex ultrasound in 23 age‐matched LT patients (11 Male, 12 Female; Mean ± SEM: Age 55 ± 2 years). Aortic pressure waves were synthesized from radial artery waveforms acquired by applanation tonometry and the use of a generalized transfer function. Novel plasma based cardiometabolic risk factors were assessed with nuclear magnetic resonance spectroscopy. Lipoprotein insulin resistance index (LPIR) was calculated as a weighted combination of concentrations and particle sizes of very low‐density, low‐density, and high‐density lipoproteins. Diabetes risk index (DRI) factors LPIR and branched‐chain amino acid levels to predict the risk of type 2 diabetes. Metabolic inflammation index (INFX) combines concentrations of the inflammation biomarker GlycA and high‐density lipoprotein particle subspecies.RESULTSMales had lower FMDBA than females (3.98 ± 0.63 vs 6.27 ± 0.43%, p < 0.01). There were no sex differences in aortic systolic pressure (Male vs Female; 129 ± 3 vs 118 ± 5 mmHg, p = 0.09), body mass index (38 ± 2 vs 36 ± 2 kg/m2, p = 0.61), LPIR (57 ± 7 vs 55 ± 7, p = 0.89), DRI (53 ± 7 vs 44 ± 6, p = 0.38), or INFX (47 ± 2 vs 54 ± 3, p = 0.13).CONCLUSIONSMales had poorer vascular endothelial function compared to females following LT, suggesting that males may be more susceptible to the development of CVD after LT. However, this increased risk cannot be explained by differences in traditional cardiometabolic risk factors. Future research should identify non‐traditional CVD risk factors that contribute to sex differences in vascular function towards implementing precision medicine for the prevention and management of CVD in LT patients.
Knowledge of anatomical variants in teachers of private universities in Santiago de Chile
Authors: Nova Baeza Pablo I. , Valenzuela Juan J. , Gold Marjorie , Bruna Alejandro , Orellana Mathias 
Published: May 2022

IntroductionHuman Anatomy is one of the pillars for the training of professionals in the health area, which generates a great challenge for the curricular profile of the teachers who teach these courses, this in relation to the different profiles proposed by each career of the health in which human anatomy is taught, where many times this must be at the service of curricular preferences and graduation profile of each career, hence well‐prepared teachers both in normal anatomy and in anatomical variants can contribute in the anatomical and later clinical training of these students. If we talk about the knowledge of anatomical variations, remember that this is defined as a change in the normal anatomy that presents an incidence in the population of no more than 10%, since, if this incidence increases, the most appropriate term to define this condition is variability. anatomical.MethodologyThis descriptive‐observational study searched through a questionnaire of eight questions, based on seven images taken from VH Dissector Pro plus a dichotomous question, which was applied to teachers of private universities in Santiago de Chile, where these They agreed to participate voluntarily through a google form. The data obtained were analyzed by the research group through the statistical method of Shapiro Wilk.ResultsAfter having surveyed 33 teachers, the results found were as follows: The percentage of the results obtained was that 0% of the participants obtained 7 points, 12% obtained 6 points, 15% obtained 5 points, 9% obtained 4 points, 36% obtained 3 points, 21% obtained 2 points, 3% obtained 1 point and 3% obtained 0 points. Regarding the gender of the participants, there was no statistically significant difference in the score obtained (p = 0.21). Finally, regarding the relationship between the score and the years of teaching experience in human anatomy, a statistically significant difference was not found in favor of teachers with more years of experience (p = 0.13).ConclusionIn relation to the results found in this study, we can affirm that many of the surveyed teachers do not have the knowledge of anatomical variants proposed in a virtual corpse, which calls us to pay attention to the fact that teachers should refine this probability of anatomical variation in their study or curricular profile, which can allow that by having a greater management of these variations they can transmit them to their students and with this make not only normal anatomy important, since clinically it has been reported that there are different anatomical variables that could have an incidence in the clinical area in any age range.
Testing a Feedback‐controlled Heated Vest to Treat Thermoregulatory Dysfunction in Persons with Spinal Cord Injury
Authors: Ortiz Vasquez Luis , Parada Wilber , Polizzi Jessica , Lee Ingrid , Bang Charlene , Bauman William , Handrakis John P. 
Published: May 2022

Study ObjectiveAfter spinal cord injury (SCI), The ability to maintain a constant core body temperature (Tcore) is compromised. Persons with higher levels of SCI (Hi‐SCI: above the first thoracic vertebrae) are far more vulnerable to hypothermia (Tcore <35°C) when exposed to cool ambient temperatures. A decrease in Tcore in persons with Hi‐SCI has been associated with impaired cognitive performance after limited exposure to cool environmental conditions (2 hours at 18°C). The objective of this pilot study is to determine the efficacy of a feedback‐controlled heated vest (HV) to minimize the decrease in Tcore and associated cognitive impairment in persons with Hi‐SCI when exposed to cool ambient conditions.MethodsThree participants with Hi‐SCI (C4‐C7, AIS A‐B) were recruited to study under two conditions [HV and non‐heated vest (NHV)] in random order on 2 separate visits when exposed to a cool challenge (CC). To obtain Tcore in a continuous manner, participants ingested a CorTempR capsule 1‐3 hours before initiation of the study. Abdominal (Tabd) and distal (Tdsk) skin temperatures were measured. Fifteen minutes of baseline (BL) data were collected while seated at thermoneutral (25°C). At the end of BL, a cognitive battery that consisted of the Montreal Cognitive Assessment (MoCA) and Stroop Color and Word Test (SCWT) was administered. Participants were then fitted with either HV or NHV and transferred into an 18°C room for 2 hours, after which the cognitive battery was once again administered.Results: During Cool Challenge (values are expressed as BL‐ CC): The decrease in Tcore was less when wearing the HV (‐0.22°C) than when wearing the NHV (‐0.54°C). The increase in Tabd was greater when wearing the HV (4.34°C) than when wearing the NHV (0.90°C). When wearing the HV, Tdsk of the fingers was higher (6.48°C HV vs. 4.20°C NHV), but not of the toes (6.46°C HV vs. 7.92°C NHV). The decrease in performance for the MoCA was less when wearing the HV (‐8.33%) than when wearing the NHV (‐43.33%). The decrease in score for the Stroop word test was less when wearing the HV (‐0.17%) than when wearing the NHV (‐3.32%). Of note, the Stroop Color and Color‐Word score increased when wearing the HV (10.12% and 5.73%, respectively) but decreased when wearing the NHV (‐0.97% and ‐4.9%, respectively).ConclusionIn persons with Hi‐SCI, our preliminary findings demonstrate the ability of the HV to minimize the expected decline in Tcore when exposed to the CC and decreased the decline in cognitive performance. While our results are quite encouraging, they require confirmation in a larger number of participants. However, once confirmed, our HV may offer persons with Hi‐SCI protection against adverse declines in Tcore when exposed to cool environmental conditions.
Pre‐fatiguing Isometric Quadriceps Exercise Impairs Contralateral Quadriceps W’ During All‐out and Not Target Torque Time to Task Failure Exercise
Authors: Lewis Matthew T. , Broxterman Ryan M. , Craig Jesse C. , Weavil Joshua C. , Laginestra Fabio G. , Jarrett Catherine L. , Bunsawat Kanokwan , Amann Markus , Richardson Russell S. 
Published: May 2022

PurposeA crossover effect of pre‐fatiguing dynamic quadriceps contractions, between contralateral legs, was recently documented, evidencing a centrally mediated negative impact on performance, assessed by time to task failure (TTF) at a target intensity. This has since been reproduced, however, whether a crossover effect exists during isometric exercise, which permits exercise in a restricted space for a more intricate assessment of muscle function, for example, by magnetic resonance imaging (MRI), has not been determined. Therefore, this study interrogated the crossover effect of isometric pre‐fatiguing quadriceps exercise with the hypothesis that a crossover would impair TTF during isometric exercise.MethodsEight healthy participants (5M/3F) performed all‐out isometric exercise tests (60 maximal voluntary contractions, 3 s contraction, 2 s relaxation) to determine the impulse above end test torque (W′) and critical torque (CT) to establish a target torque that invoked a TTF between 8‐15 min, as defined by the torque‐duration relationship (TTF = W’/(target torque – CT)). Once established, target torque TTF and all‐out exercise CT and W’ were measured with and without pre‐fatiguing all‐out quadriceps exercise in the contralateral leg to assess the crossover effect.ResultsTTF averaged 9.8 ± 0.4 min and, interestingly, was not altered by pre‐fatigue in the contralateral leg (11.9 ± 1.0 min, p = 0.34). CT was not different in control vs. pre‐fatigue (73 ± 8 vs. 76 ± 10 N*m, p= 0.34) but W′, an indicator of exercise capacity, was reduced by 25% (6200 ± 1200 vs. 4700 ± 900 N*m*s, p = 0.02).ConclusionsThese data document a crossover effect of pre‐fatiguing isometric quadriceps exercise on subsequent contralateral quadriceps isometric exercise, but only during all‐out exercise and not target torque TTF. Furthermore, as a consequence of the unique experimental approach, utilizing a dual‐leg isometric ergometer designed to fit in a MRI, the negative impact of contralateral limb pre‐fatigue (e.g. increased afferent feedback) on W′ has been documented for the first time.