bluuebunny/crossref_metadata_2025_split huggingface dataset:
The comparative study of endogenous growth inhibiting factors of pro‐ and eukaryotic cells
Authors: Dzidziguri Diana , Rukhadze Marina , Bakuradze Ekaterine , Modebadze Irina , Gorozia Ilia , Abashidze Vera 
Published: June 2021

Tumour cells are often resistant to signals which inhibit growth of normal cells. Avoiding such control mechanisms may contribute to malignant transformation.The mammalian normal kidney cells contain the tissue‐specific thermostable protein complex (TPC) suppressing division of normal and transformed epitheliocytes on the basis of our research. The suppressive action of TPC is revealed at the level of genes activity, which results in the reduction of mitotic index of homotypic cells. The low‐molecular active components (10 ‐12 kD) of TPC identified in cells of kidney of phylogenetically distant eukaryotes have analogous characteristics. They do not represent in the human kidney cancer cells.The goal of the presented work was the comparative study of TPC of pro‐ and eukaryotic cells.ResultsThe comparative study has been shown that A. Oxydans as well as animal cells contain TPC, which inhibit the proliferation of homological cells in culture. The inhibiting effect of bacterial TPC is not revealed on the whole animal cells. We have shown that the action of bacterial TPC is apparent only at the level of isolated nuclei.ConclusionIt is determined that components of bacterial TPC concern family of conservative proteins. In comparison with eukaryotic cells active hydrophilic components of bacterial TPC have a different conformation, which is responsible to its specificity.
Peer teachers introducing anatomy to first year medical students
Authors: Kiene Jason , Lasek Ray , Wish‐Baratz Susanne , Freeman Barbara 
Published: June 2021

Systems approaches to medical education have changed the approach to anatomy from a concentrated "course" to a longitudinal, integrated theme in many medical school curricula. Thus, students may be forced to learn anatomy regionally without a sense of how different body systems are integrated. Furthermore, teaching by senior students has been found to be an effective educational method and can augment faculty resources in a small‐group curriculum. These issues led to our study question: Can a 10 hour introductory anatomy course taught solely by 2nd year medical students in a small‐group format improve the preparation of 1st year medical students for the demands of a systems‐based anatomy course?We had four goals:1) Provide a basic framework for the anatomy of major body systems2) Develop teaching and learning modules that show the relationship between anatomic structures, physical diagnosis and radiology3) Utilize peer‐teaching4) Promote interest in anatomyStudents finished 90% of each session. The average score on the cumulative quiz was 93%. Surveys indicated extremely high satisfaction with the course, overwhelmingly positive feedback about the peer teachers, and good pre‐class preparation by students. We saw no statistical difference in scores on the subsequent curricular anatomy assessments. Overall, goals 1‐4 were successfully met. However, incremental knowledge was not reflected in test scores.
Specific Silencing of Janus Kinases on Proliferating T Lymphocytes
Authors: Gómez‐Valadés Alicia , Llamas Maria , Gómez‐Casajús Lluís , Mascaró Cristina 
Published: June 2021

Jak3 is the only janus kinase among the four family members (Jak1. Jak2, Jak3, and Tyk2) which is predominantly expressed in haematopoietic linage. Small molecule inhibitors of the Jak's are being actively studied for immunosuppressive therapies. Nevertheless, they have not shown a selective pattern versus the different family members and implications over the therapeutic efficiency of a JAK3‐specific antagonist remain unclear.In this study we aim to investigate the effects of specific Jak3 inhibition using the powerful and specific iRNA technology. Specific sequences against human Jak1 and Jak3 were designed and successfully transfected into primary human T lymphocytes. Upon siRNA treatment, specific and stable silencing was observed at the RNA and protein level. After selective Jak abrogation, IL‐2‐induced proliferation was potently inhibited, and cell death was clearly induced. These effects on cell viability were dose dependent, in correlation with silencing effect. Nevertheless, we never observed an additive effect over the viability when Jak1 and Jak3 (whose heterodimerization is required to transduce IL‐2 signalling) were co‐silenced. These data indicate that a selective Jak3 inhibitor can, per se, modulate IL‐2 signalling, reinforcing the idea that a Jak3 selective antagonist could report therapeutic benefits as immunosuppressant.
NK cell function is depressed in Gulf War Illness
Authors: Whistler Toni , Fletcher Mary Ann , Lonergan William , Klimas Nancy G 
Published: June 2021

Gulf War Illness remains a serious health consequence for veterans deployed during the first Gulf War. Our understanding of the health consequences remains inadequate, and this is of concern with another deployment occurring now. Chronic immune cell dysfunctions have been reported, although the literature is not uniform.We used an exercise stress paradigm to determine differences in immune measures and gene expression profiles between the baseline, immediately after exercise and 4 hours later, in GWI subjects compared to sedentary veteran controls. Repeated‐measures ANOVA showed that there were statistically significant differences for NK cytotoxicity and NK cell subsets between cases and controls. Linear regression analysis correlating NK cell numbers to expression profiles showed high correlation of genes relating to NK cell function. We found the intracellular perforin levels trended lower and showed a flatter profile in GWI cases than controls, as did the expression levels of the perforin gene, PRF1.GWI patients demonstrated impaired immune function, involving Th2 and proinflammatory cytokines, cytotoxic NK and T cells, and dysregulated mediators of the stress response including salivary cortisol, compared to control subjects. An important observation was that the exercise challenge augments these differences, with the most significant effects observed immediately after the stressor.
Vascular Cell Adhesion Molecule (VCAM‐1) predicts Atrial Fibrillation after On‐Pump Heart Surgery
Authors: Lavandero Sergio , Verdejo Hugo , Garcia Lorena , Becerra Elia , Roldan Juan , Chiong Mario , Mellado Rosemarie , Zalaquet Ricardo , Braun Sandra , Corbalan Ramon 
Published: June 2021

Post‐Operative Atrial Fibrillation (POAF) occurs in 30% of patients after on‐pump heart surgery (OPHS). POAF is associated to elevated inflammatory markers; whether this reflects systemic inflammation or local atrial changes is unknown.Methods70 patients in sinus rhythm submitted to elective OPHS were included. Systemic inflammatory and oxidative stress markers were measured at baseline and 72 h after surgery. During the procedure, a sample of right atrial appendage was obtained. EKG was monitored for 72 h after surgery for event adjudication.Results37% of the patients developed POAF. Systemic inflammatory and oxidative stress markers did not differ between groups. Baseline serum VCAM‐1 was higher in patients who developed POAF and remained an independent predictor for POAF (OR 5.06, p = 0.02) after adjustment. No association was observed between serum VCAM‐1 and VCAM‐1 expression levels in right atrial appendage.ConclusionIn patients undergoing OPHS, elevated VCAM‐1 serum levels predict a higher risk for POAF. This elevation is not related to increased expression of adhesion molecules in right atrial, suggesting that systemic inflammation rather than local changes pre‐exist in patients who develop the arrhythmia.FONDECYT 1070641, DI‐06‐09‐2, FONDAP 15010006
A case‐study of fucoxanthin uptake kinetics
Authors: Craft Neal E. , Arredondo‐Vega Francisco X. 
Published: June 2021

Fucoxanthin (FX), a carotenoid in seaweed, has been reported to increase lipid oxidation in adipose tissue leading to weight loss. Little is known about FX kinetics and biochemical activity. We initiated a case study examining the uptake of FX into the blood of an adult male.ObjectiveTo monitor FX and metabolite concentrations in serum following FX consumption.MethodsBlood was collected at 0, 4, 8, 24, 48, 72, 96 hrs. FX was consumed as softgels post blood draw (0 hr) and on days 1‐4. On day 0, 11mg of trans‐FX was consumed and 6.6mg on each successive day. Serum was harvested each day of blood collection and frozen. On day 4, blood samples were analyzed by HPLC using a C30 gradient separation with DAD. Based upon the results, no additional blood was collected.ResultsAll of the major carotenoids reported in human blood plus FX and a metabolite, Fucoxanthinol (FXOH), were measured. FXOH was observed in the blood at 4hr (2.6 ng/mL) and peaked at 8hr (9.6 ng/mL) and returned to 2.2 ng/mL by 24hr after the initial FX consumption. FXOH was measured in the serum on each day (0.8‐1.1 ng/mL) but did not accumulate in the blood with each day of consumption. Blood and urine were also tested for conjugates of FX or FXOH.DiscussionFX was not measurable in the blood samples. FXOH appearance and decline in serum was more rapid than reported for less polar carotenoids and it does not appear to accumulate in its endogenous form in this tissue.
Rho‐kinase inhibition abolishes the vasoconstrictor response to hypoxia in the infant piglet pulmonary arterial circulation
Authors: Balasundaram Naveen , Chowdhary Paraag , Titus James , Jagannath Anand , Carillo Kathleen , Myers Jeff L 
Published: June 2021

We examined the effects of the rho‐kinase inhibitor fasudil on the regional response of the infant pulmonary arterial (PA) circulation to hypoxia. 15 two week old piglets were instrumented to record PA pressure (PAP). Control animals (n=7) were exposed to hypoxia (FiO2 = 0.05). Treated animals (n=8) were infused with fasudil (5mg/Kg) before and during hypoxia. Input mean impedance (Zm, reflecting distal arteriolar vasoconstriction) and characteristic impedance (Zo, reflecting proximal arteriolar opposition to flow) were calculated.Hypoxia caused a potent vasoconstrictor response distally (increased Zm). Zo was unchanged indicating no alteration of the proximal circulation. Pre‐treatment with fasudil completely abolished the increase in Zm and PAP indicating that the distal vasoconstrictor response is rho‐kinase dependent. Rho‐kinase inhibitors may be an effective therapy for hypoxic pulmonary hypertension in infants, but may be limited by its effect on systemic blood pressure. Funded by Dept. of Surgery, Mass. Gen. Hosp.
Aging and vascular endothelial cell senescence: potential role of SIRT1 in development of inflammation and dysfunction
Authors: Blimline Mark , Seals Douglas , Nelson Keri , Rippe Catarina 
Published: June 2021

Aging leads to vascular endothelial dysfunction, but the mechanisms involved are incompletely understood. We assessed the effects of aging on endothelial cell (EC) senescence in vivo and the possible role of the anti‐senescence and anti‐inflammatory deacetylase, SIRT1, in vitro. Compared with young adult (5 mo) mice, old (30 mo) mice had reduced endothelium‐dependent dilation and a higher % of aortic EC that stained for the senescence marker p16INK4a (31 vs. 6). "Aged" cultures of human aortic EC (HAEC) (35±2 population doublings, PDL) had a higher % of cells stained for p16INK4a (46 vs. 7) and (beta)‐galactosidase, a 2nd marker of senescence (57 vs. 6), than "young" cultures (20±1 PDL). SIRT1 expression was 55% lower in senescent HAEC (0.45±0.08 vs. 1.00 ± 0.10 AUs, P<0.002). Senescent HAEC demonstrated reduced expression of the anti‐inflammatory proteins interleukin‐10 (0.6±0.05 vs. 1.0±0.2 AUs, P<0.05) and interleukin‐1 receptor‐α (0.7±0.05 vs. 1.0±0.2 AUs, P<0.05), and increased expression of the inflammatory protein monocyte chemoattractant protein‐1 (1.6±0.1 vs. 1.0±0.1 AUs, P<0.005). In conclusion, the % of senescent arterial EC in vivo is greater in old age. A decrease in SIRT1 may play an important role in EC senescence and contribute to development of vascular endothelial inflammation and dysfunction.Swedish Research Council; NIH AG006537, AG013038, AG022241, RR00051
Transforming Growth Factor‐β Regulates Valve Interstitial Cell Growth in Vitro
Authors: Li Chen Xi , Gotlieb Avrum I 
Published: June 2021

BackgroundThe effect of transforming growth factor beta (TGF‐β) on VIC growth independent of injury is poorly understood. We showed that in the early stages of VIC wound repair TGF‐β promotes VIC proliferation and repair (A. Liu et al. Am J Pathol 2008; 173:1275–1285). In contrast, we found that under normal non‐wound conditions TGF‐β decreases cell number, alters cell morphology, and increases cell adhesion. In this study we set out to investigate the molecular mechanisms responsible for the latter observations.Materials and MethodsSB431542 is a potent inhibitor of the TGF‐β receptor I. Low density cultures were treated with TGF‐β or SB431542 and their respective controls. The extent of retinoblastoma protein (pRb) phosphorylation and expression of cyclin D1, CDK4, and p27 were compared using Western Blotting.ResultsTGF‐β treatment inhibits VIC proliferation by under‐phosphorylation of p‐Rb at Ser807/811, which could be reversed by receptor signaling inhibition. There is also a concomitant downregulation of cyclin D1/CDK4 and upregulation of their inhibitor, p27. The decrease in cell number caused by exogenous TGF‐β can be abolished by the inhibitor.ConclusionTGF‐β regulates VIC growth in vitro by inhibiting proliferation in low‐density monolayer while stimulating proliferation at the wound edge following injury.
Aquaporin‐9 expression in malignant glioma
Authors: Jelen Sabina Katarzyna , Rützler Michael 
Published: June 2021

Recent studies described enhanced expression of the water channel aquaporin 9 (AQP9) in biopsies of glioblastoma patients. This may indicate a function for AQP9 in glioma progression as water channels are known to contribute to cell migration. Furthermore, AQP9 is a glycerol and lactate channel and could play a role in the energy metabolism of malignant glioma cells.Glial tumors usually consist of several cell types, including malignant glial cells, endothelial cells, microglia and other cells of the immune system. Currently, the specific cellular localization of AQP9 has not been determined. The aim of our studies was to determine the cellular expression of AQP9 in glioblastoma biopsies. Furthermore, we are currently investigating the cellular expression of AQP9 in various murine models of glioblastoma.Human tissue revealed positive AQP9 labeling in a subpopulation of tumor cells. Moreover, we discovered strong immunolabeling of AQP9 co‐localized with the neutrophil marker CD15. Similar to the situation in human tumors, AQP9 was expressed in neutrophils invading murine Gl261 derived tumors. However, Gl261 derived cells did not express AQP9.We conclude, that AQP9 is expressed in human glioma cells and tumor associated neutrophils. Furthermore, the Gl261 murine model of glioblastoma may be suitable to study a function of AQP9 in tumor associated neutrophils.Study supported by Lundbeck Foundation
Sodium channel activator‐induced neurite outgrowth is NMDA receptor dependent and involves a TrkB‐PLCγ‐PI3K‐Akt pathway
Authors: Jabba Sairam V , Murray Thomas F 
Published: June 2021

Calcium influx through N‐methyl D‐aspartate receptors (NMDAR) regulates signaling cascades that underlie activity‐dependent neuronal development, including the expression and release of BDNF with activation of TrkB pathway. BDNF‐TrkB mediated neuronal development primarily involves three pathways: the PI3K, MAPK and PLCγ systems. Voltage‐gated sodium channel (VGSC) activators promote neuronal development by increasing [Na+]i and upregulating NMDAR function. We examined the effect of the sodium channel activator veratridine (VRT) on neurite outgrowth (NOG) and BDNF‐TrkB signaling in DIV1 cerebrocortical neurons. VRT enhanced NOG and this response was dependent on NMDARs and TrkB signaling. Inhibitors of NMDAR (MK‐801), TrkB (K‐252a), PI3K (LY294002), and PLCγ (U73122) inhibited VRT‐enhanced NOG. VRT increased [Na+]I and [Ca2+]i. VRT‐induced elevation of Ca2+ involved VGSCs, NMDARs and PLCγ sensitive intracellular Ca2+ stores. VRT stimulated phosphorylation of TrkB (Y816: activates PLCγ) and Akt, a downstream effector of the BDNF‐TrkB‐PI3K pathway. VRT‐induced Akt phosphorylation involved VGSC‐NMDAR‐CaMKK‐PI3K signaling. VRT also activated ERK1/2 and CREB: downstream effectors of the MAPK pathway. These data suggest that VRT‐enhanced NOG involves elevation of [Na+]i, and activation of NMDAR‐BDNF‐TrkB signaling with subsequent engagement of downstream PLCγ, PI3K and MAPK pathways.NIH RO1 NS053398‐06
Acrolein‐induced hepatotoxicity: role of mitochondrial dysfunction and endoplasmic reticulum stress
Authors: Joshi‐Barve Swati , Avila Diana , Zhang Jingwen , Barve Shirish , McClain Craig 
Published: June 2021

BackgroundAcrolein is a common environmental, food and water pollutant and a major component of cigarette smoke. It is produced endogenously by the metabolism of several drugs and amino acids and has also been identified as both a product and initiator of lipid peroxidation. Acrolein is known to be cytotoxic to many cell types including hepatocytes; however the underlying molecular mechanisms are not fully understood.MethodsHuman hepatic cells (HepG2) were used to measure acrolein‐induced hepatotoxicity, and to study endoplasmic reticulum stress (ERS) and mitochondrial death pathways and the induction of apoptosis.Results and ConclusionsAcrolein exposure caused a dose‐dependent decrease in intracellular antioxidant glutathione and a loss of survival of hepatic cells. Cell death was apoptotic at moderate and necrotic at higher cytotoxic concentrations of acrolein. Additionally, acrolein disrupted mitochondrial integrity/function as seen by fluorescence microscopy and ATP depletion. Acrolein activated ERS proteins PERK, eIF2α and ATF3, 4, 6, and also activated the kinases JNK and p38 MAPK. We postulate that acrolein induced disruption of both mitochondria and ER contributes to hepatotoxicity. Our study defines basic mechanisms involved in liver injury due to oxidative stress molecules and reactive aldehyde pollutants such as acrolein. This study was funded by NIH and VA.
Proanthocyanidin protects intestine and remote organs against mesenteric ischemia/reperfusion injury
Authors: Sizlan Ali , Guven Ahmet , Uysal Bulent , Yanarates Omer , Atim Abdulkadir , Oztas Emin , Cosar Ahmet , Korkmaz Ahmet 
Published: June 2021

BACKGROUNDIntestinal ischemia/reperfusion (IR) induces a systemic inflammatory response and releases harmful substances that may affect the function and integrity of distant organs such as lung, liver, and kidney. We conducted this study to find out if proanthocyanidins (PA) has protective effects against mesenteric IR injury and mesenteric IR‐induced intestinal and distant organ injury.MATERIALS AND METHODSThirty‐two Sprague‐Dawley rats were divided into four groups: control, control + PA, IR, IR + PA. The IR and IR + PA groups were subjected to mesenteric arterial ischemia for 60 min and reperfusion for 6 h. The Control + PA and IR + PA groups were administered PA (100 mg/kg/day via oral gavage) for 7 days prior to injury insult. We collected ileal and distant organ tissues, such as pulmonary, hepatic, and kidney specimens to measure tissue levels of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx), and nitrite plus nitrate (NO(x)), and we then evaluated histological changes.RESULTSIn the IR group, significant increases in MDA and NO(x) levels and significant increases in SOD and GPx activities of intestine, liver, kidney, and lung were observed. The MDA and NO(x) levels were significantly lower, as were the SOD and GPx activities in the IR + PA group than that in the IR group. Although the intestine and distant organs damage scores were significantly higher in the IR group, these injuries were prevented by PA in the IR + PA group.CONCLUSIONSThis study demonstrates that PA has a significant effect in the protection of the intestine and the remote organs against mesenteric IR injury.
Hyperbaric oxygenation reduces exercising forearm blood flow in humans
Authors: Casey Darren P. , Joyner Michael J. , Claus Paul L. , Bigelow Maureen L. , Fuqua William R. , Balgeman Jon R. , Curry Timothy B. 
Published: June 2021

Hypoxia during exercise augments vasodilation and blood flow to ensure adequate delivery of O2 to active muscles. However, the impact of hyperoxia on skeletal muscle blood flow during exercise is poorly understood. Therefore, we tested the hypothesis that the hyperemic response to exercise with hyperbaric hyperoxia would be blunted compared to exercise during normoxia. Seven subjects (6M/1F; 26 ± 2 years) performed forearm exercise (20% of maximum) under normoxic and hyperoxic conditions. Forearm blood flow (FBF; ml/min) was measured using Doppler ultrasound. Forearm vascular conductance (FVC; ml/min/100mmHg) was calculated from FBF and blood pressure (mmHg; brachial arterial catheter). Studies were performed in a hyperbaric chamber with the subjects supine at 1 ATA (sea level) and 2.8 ATA while breathing normoxic (21% O2, 1 ATA; FIO2 ≈ 150 mmHg), hyperbaric normoxic (7% O2, 2.8 ATA, FIO2 ≈ 150 mmHg) and hyperoxic (7% O2, 2.8 ATA, FIO2 ≈ 2100 mmHg) gas. The change in FBF and FVC (Δ from rest) during exercise under normoxia and hyperbaric normoxia did not differ (P > 0.05). However, the ΔFBF and ΔFVC during exercise under hyperoxia were attenuated by ~18–29% compared to both normoxic conditions (P ≤ 0.01). Our data suggest that exercise hyperemia in skeletal muscle is highly dependent on oxygen availability during hyperoxia as well as hypoxia.NIH HL46493 (MJJ), AR55819 (DPC) and RR‐024150.
Practical analysis of type 1 aortic arch anatomy – Towards a standardized arch endograft
Authors: Finlay Adrienne , Johnson Marjorie , Forbes Thomas 
Published: June 2021

Endovascular repair of aortic arch pathologies currently requires custom‐made endografts to reflect an individual's anatomy, causing a treatment delay. This study's purpose is to identify common patterns in the anatomy of the type 1 aortic arch and its branches to aid in the development of an off‐the‐shelf endograft.TeraRecon 3D imaging software was used for morphological assessment of CT scans from 45 patients (26 M, 19 F; mean age 68). A total of 13 measurements were made including diameter, distance and orientation of vessels. Statistical analysis indicated various trends. The diameter of the aorta was larger more proximally (closer to the coronary arteries), the distance between the inominate artery (IA) and the left common carotid artery (LCC) was approximately half the distance measured between the LCC and the left subclavian artery (LSC). Branch ostia diameters consistently ranked in the following order IA>LSC>LCC. Lastly, the LCC orientation, with respect to the other two vessels, was within a 50° range.This study provides useful information for the production of an arch endograph prototype reflecting the anatomy of the majority of patients. Prospective validation of this design is required.Grant Funding Source: Departmental