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51.
In Vitro Differentiation and Expansion of Human Pluripotent Stem Cell-Derived Pancreatic Progenitors
Recent progress in understanding stem cell biology has been remarkable, especially in deciphering signals that support differentiation towards tissue-specific lineages. This achievement positions us firmly at the beginning of an era of patient-specific regenerative medicine and human disease modeling. It will be necessary to equip the progress in this era with a reliable source of self-renewing progenitor cells that differentiate into functional target cells. The generation of pancreatic progenitors that mature in vivo into functional beta-cells has raised the hope for new therapeutic options in diabetes, but key challenges still remain including the production of sufficient numbers of cells for research and transplantation. Recent approaches to this problem have shown that the presence of organ- and stage-specific mesenchyme improves the generation of progenitors, from endoderm to endocrine cells. Alternatively, utilization of three-dimensional culture may improve the efficiency and yield of directed differentiation. Here, we review the current knowledge of pancreatic directed differentiation and ex vivo expansion of pancreatic progenitors, including recent advances in differentiation strategies for the generation of pancreatic progenitors, and we discuss persistent challenges which will need to be overcome before personalized cell-based therapy becomes a practical strategy. 相似文献
52.
Jakub Wojcieszak Dariusz Andrzejczak Bożena Szymańska Jolanta B. Zawilska 《Pharmacological reports : PR》2019,71(6):977-982
BackgroundSynthetic cathinones (SCs) form one of the most prominent group of the New Psychoactive Substances. SCs enhance central dopaminergic and noradrenergic neurotransmission, and are used as substitutes for illicit psychostimulants, namely cocaine, amphetamine, and methamphetamine. Changes in the expression of immediate early genes (IEGs) in the striatum underlie the addictive potential of drugs of abuse belonging to distinct pharmacologic groups. This work was aimed to assess the impact of acute administration of the prominent SCs on the mRNA levels of IEGs in the mouse striatum.MethodsEffects of 3,4-MDPV, 2,3-MDPV, α-PVP, PV8, PV9, methcathinone (MC) and 3-fluoromethcathinone (3-FMC) on the mRNA levels of ten IEGs, one and two hours after exposure, were measured in the mouse striatum using the quantitative RT-PCR technique.ResultsAll SCs used in the study produced increased mRNA levels of the following IEGs: Areg, c-fos, Csrnp1, Dusp1, Dusp14, Egr2, Egr4 and FosB. Additionally, the majority of SCs increased the expression of Homer1 and c-jun. The magnitude of observed changes varied by the drug, analyzed gene and, in many cases, by time after administration.ConclusionsThis study demonstrates that SCs increase the expression of IEGs in the mouse striatum, which may lead to a plethora of effects, as proteins encoded by the analyzed genes are involved in diverse actions, including an acute response to the drug and the neuroplasticity underlying the development of addiction. 相似文献
53.
54.
Gaudet MM Falk RT Stevens RD Gunter MJ Bain JR Pfeiffer RM Potischman N Lissowska J Peplonska B Brinton LA Garcia-Closas M Newgard CB Sherman ME 《The Journal of clinical endocrinology and metabolism》2012,97(9):3216-3223
Context: Endometrial cancer is associated with metabolic disturbances related to its underlying risk factors, including obesity and diabetes. Identifying metabolite biomarkers associated with endometrial cancer may have value for early detection, risk assessment, and understanding etiology. Objective: The objective of the study was to evaluate the reliable measurement of metabolites in epidemiological studies with nonstandardized blood collection; confirm previously reported correlations of metabolites with body size; and assess differences in metabolite levels between cases and controls. Design: This was the Polish Endometrial Cancer Study (2001-2003). Setting: This study was a population-based case-control study. Patients: Patients included 250 cases and 250 controls. Intervention: The intervention included the measurement of serum metabolite levels of 15 amino acids, 45 acylcarnitines, and nine fatty acids. Main Outcome Measure: The main outcome measure was endometrial cancer. Results: Body mass index was correlated with levels of valine (r = 0.26, P = 3.4 × 10(-5)), octenoylcarnitine (r = 0.24, P = 1.5 × 10(-4)), palmitic acid (r = 0.26, P = 4.4 × 10(-5)), oleic acid (r = 0.28, P = 9.9 × 10(-6)), and stearic acid (r = 0.26, P = 2.9 × 10(-5)) among controls. Only stearic acid was inversely associated with endometrial cancer case status (quartile 4 vs. quartile 1: odds ratio 0.37, 95% confidence interval 0.20-0.69, P for trend = 1.2 × 10(-4)). Levels of the C5-acylcarnitines, octenoylcarnitine, decatrienoylcarnitine, and linoleic acid were significantly lower in cases than controls (odds ratios ranged from 0.21 to 0.38). Conclusions: These data demonstrate that previously reported variations in metabolomic profiles with body mass index can be replicated in population-based studies with nonfasting blood collection protocols. We also provide preliminary evidence that large differences in metabolite levels exist between cases and controls, independent of body habitus. Our findings warrant assessment of metabolic profiles, including the candidate markers identified herein, in prospectively collected blood samples to define biomarkers and etiological factors related to endometrial cancer. 相似文献
55.
Katarzyna Marchlewska Krzysztof Kula Renata Walczak-Jedrzejowska Wojciech Kula Elzbieta Oszukowska Eliza Filipiak Tomasz Moszura Jolanta Slowikowska-Hilczer 《Archives of Medical Science》2013,9(1):139-145
Introduction
Connexin 43 (Cx43) mediates the effect of thyroid hormone on Sertoli cell maturation in vitro. We investigated the influence of triiodothyronine (T3) administration on Cx43 expression in relation to the progress in seminiferous tubule maturation.Material and methods
Male rats were daily injected with 100 µg T3/kg body weight from birth until postnatal day (pnd) 5 (transient treatment – tT3) or until pnd 15 (continuous treatment – cT3) or solvent – control (C). On pnd 16 serum hormone levels, body and testes weight, seminiferous tubule morphometry, Cx43 immunostaining and germ cell degeneration were investigated. Cx43 expression was also assessed in six 50-day-old adult untreated rats.Result
tT3 increased 2.6-fold serum level of T3, testes weight, and seminiferous tubule diameter, and induced maturation-like dislocation of Cx43 expression from the apical to the peripheral region of Sertoli cell cytoplasm. In addition, incidence of Cx43-positive tubules declined from 86% in C to 46% after tT3, being similar to the adult value (30% of tubules Cx43-positive). In turn, cT3 increased serum T3 level 12-fold, and decreased body weight. Seminiferous tubules became shortened and distended, Sertoli cell cytoplasm vacuolated, Cx43 expression had minimal intensity and germ cell degeneration increased.Conclusions
Cx43 might intermediate a short and transient stimulatory effect of T3 on seminiferous tubule maturation that disappeared together with exposure to the toxic effect of a continuously high level of the hormone. 相似文献56.
Agnieszka Held Ewa Janiszewska Justyna Czerepiska Jolanta Kowalska-Ku 《RSC advances》2020,10(17):10144
V-containing mesoporous silica with 3D structure was prepared by a hydrothermal procedure using NH4VO3 as the vanadium precursor and with varied reaction mixture pH values (pH = 3 and pH = 5). The combined use of DR UV-vis and H2-TPR techniques confirmed the successful incorporation of vanadium into the structure of the mesoporous silica material. The number of acid sites, evidenced by ammonia TPD, strongly correlates with the vanadium content. Propene oxidation with N2O revealed the noticeable activity of the synthesised vanadium-containing mesoporous materials in epoxidation reactions. The activity of the synthesized vanadosilicates is compared with the performance of vanadium-supported catalysts (on mesoporous silica of 3D structures) prepared by wet-impregnation method. On the basis of TOF analysis indicating the activity of particular vanadium ions, it was evidenced that although the presence of isolated V species is crucial in propene epoxidation, the availability of the active species is of paramount importance for proper vanadium utilization.Novel promising vanadium catalysts based on mesoporous silica of 3D structure, namely KIT-6, SBA-12, and MCF, for the direct propene epoxidation with N2O. 相似文献
57.
Hepcidin is the key regulator of iron metabolism. Iron supplementation is often introduced in dialyzed patients to replete or to maintain iron stores, particularly in patients treated with erythropoietic-stimulating agents. The present study was aimed to assess possible relation between hepcidin and erythropoietin therapy, with particular attention being paid to erythropoietin-hyporesponsiveness in hemodialyzed patients. Prohepcidin and hepcidin were studied using commercially available kits from DRG Instruments GmbH, Germany (ELISA method) and Bachem, UK (RIA method). TNFα and IL-6 were studied using kits from and R&D (Abington, UK), and hsCRP was studied using kits from American Diagnostica, USA. Hyporesponsive patients to erythropoietin therapy had significantly lower serum albumin, cholesterol, LDL, hemoglobin, hematocrit, and residual renal function, and significantly higher serum ferritin, hsCRP, IL-6, TNFα, and erythropoietin dose. The difference in serum prohepcidin and hepcidin did not reach statistical significance; however, there was a tendency toward higher values of both prohepcidin and hepcidin in hyporesponsive patients. In conclusion, though hyporesponsiveness to erythropoietin therapy occur in dialyzed patients, it is mainly associated with subclinical inflammation than with hepcidin excess. Further studies are needed to develop a reliable and reproducible assay to elucidate the potential contribution of hepcidin to hyporesponsiveness during erythropoietin therapy. 相似文献
58.
Donatas Vasiliauskas Rimantas Benetis Lina Jasiukeviciene Vytautas Grizas Jolanta Marcinkeviciene Ramunas Navickas 《Scandinavian cardiovascular journal : SCJ》2013,47(3):142-148
Aim. The aim of this prospective randomized study was to evaluate the impact of long-term aerobic exercise training on respiratory function, left ventricular systolic function and remodeling in patients with coronary heart disease and ischemic heart failure after successful angioplasty. Design. Patients (n=185) have undergone Doppler echocardiography and ergospirometry. Ninety-five patients practiced 6 month-term aerobic exercise training, less by 10% to their anaerobic threshold. Ninety patients were studied as controls. They were given only drug treatment without training. Measurements were repeated after 6 and 12 months. Results. Training group patients after 6 months showed significant (p<0.05) improvement in exercise capacity, oxygen consumption and ventilating equivalents. The Doppler echocardiographic findings revealed significant (p<0.05) improvement in ejection fraction, left ventricular and atria morphometric data. Improved ergospirometric and echocardiographic data were established after 12 months, too. Conclusions. Long-term aerobic exercise training is an effective and workable measure improving respiratory efficiency, left ventricular systolic function, attenuating negative remodeling and stopping further progression in patients with coronary heart disease and chronic heart failure after successful angioplasty. 相似文献
59.
Günter Christ Thomas Hafner Jolanta M. Siller-Matula Marcel Francesconi Katharina Grohs Eva Wilhelm Andrea Podczeck-Schweighofer 《Thrombosis research》2013