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1.
Tarek Bisat Terry R. Brown Claude J. Migeon Gary D. Berkovitz 《In vitro cellular & developmental biology. Plant》1989,25(9):806-812
Summary Because the measurement of aromatase activity in cultured human genital skin fibroblasts has been proposed as a means of studying
estrogen production in men, we investigated the influence of culture conditions on aromatase activity.
Genital skin fibroblasts were seeded onto culture plates at a density of 1×106 cells/plate and aromatase activity was determined over a 1-mo. period. Enzyme activity rose slowly over the first 14 d but
then rose rapidly to a 10-fold higher plateau by Day 28. The rise in aromatase activity was similar whether activity was normalized
for protein or for DNA content. When cells were seeded at the usual density of 1×106 or at 0.25×106 cells/plate, aromatase activity was consistently lower during the first 2 wk in cells plated at lower density, but thereafter
the levels of enzyme activity in the two groups converged. In cells plated at the lower density, the lower activity observed
in the first 2 wk was associated with a lower V
max
. Preincubation of cells plated at one density with conditoned medium from cells plated at the other density did not change
the relatve levels of activity in the two groups. By contrast, dihydrotestosterone (DHT) receptor binding and 5α-reductase
activity were similar at all time points, despite differences in plating density.
In additional experiments, the culture medium was replaced daily rather than every 3rd d, and aromatase activity was assayed
on Day 7. In cells fed daily, DNA and protein content were twice that of cells fed every 3rd d. By contrast, aromatase activity
declined to 30% of the in the latter group. DHT and dexamethasone receptor binding and 5α-reductase activity were similar
in the two groups.
In summary, factors such as plating density, culture density, and frequency of media replacement dramatically influence aromatase
activity in cultured human genital skin fibroblasts. Therefore, the interpretation of aromatase activity data obtained from
cultured cells in relation to physiologic or pathologic states should be viewed with appropriate caution.
The work was supported in part by grants R01 DK 35339 and R01 DK 00180 from the National Institutes of Health, Bethesda, MD,
and by RR 00035 from CLINFO Systems at the Johns Hopkins University School of Medicine, Baltimore, MD. 相似文献
2.
1′-Aza-carbocyclic-2′, 3′-dideoxyuridine, 3′-deoxythymidine and 2′, 3′-dideoxycytidine were synthesized from 1-aminopyrrolidine intermediate 13 and evaluated as anti-HIV agents in MT-4 cells. 相似文献
3.
A unified framework to model the potential and realized distributions of invasive species within the invaded range 下载免费PDF全文
Tarek Hattab Carol X. Garzón‐López Michael Ewald Sandra Skowronek Raf Aerts Hélène Horen Boris Brasseur Emilie Gallet‐Moron Fabien Spicher Guillaume Decocq Hannes Feilhauer Olivier Honnay Pieter Kempeneers Sebastian Schmidtlein Ben Somers Ruben Van De Kerchove Duccio Rocchini Jonathan Lenoir 《Diversity & distributions》2017,23(7):806-819
4.
Sphingolipids have emerged as molecules whose metabolism is regulated leading to generation of bioactive products including ceramide, sphingosine, and sphingosine-1-phosphate. The balance between cellular levels of these bioactive products is increasingly recognized to be critical to cell regulation; whereby, ceramide and sphingosine cause apoptosis and growth arrest phenotypes, and sphingosine-1-phosphate mediates proliferative and angiogenic responses. Sphingosine kinase is a key enzyme in modulating the levels of these lipids and is emerging as an important and regulated enzyme. This review is geared at mechanisms of regulation of sphingosine kinase and the coming to light of its role in disease. 相似文献
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7.
Manal M. Elbandrawy Osama Sweef Doaa Elgamal Tarek M. Mohamed EhabTousson Rehab M. Elgharabawy 《Saudi Journal of Biological Sciences》2022,29(5):3871
BackgroundType 2 diabetes (T2DM) is a chronic metabolic disorder. Although therapeutic pharmaceutical agents continue to advance, herbal medicines are potential complementary treatments for the promotion of glucose homeostasis, with minimal adverse effects. Conventionally, ellagic acid (EA) has been utilized for the therapy of a range of pathologies owing to its anti-inflammatory and anti-diabetic actions.ObjectiveThe aim of this study is to determine the activity of EA on serum α-amylase and lipase titers, and on pancreatic tumor necrosis factor-α (TNF-α), proliferating cell nuclear antigen (PCNA) and interleukin-6 (IL-6) concentrations using the streptozocin-induced T2DM rodent model.MethodsEA extract synthesized from fresh strawberry fruit was employed for therapy. 50 adults male Wistar rats were randomized into either control, EA, diabetic, co-treated or post- treated cohorts.ResultsEA diminished fasting blood glucose levels, altered lipase, amylase, IL-6, PCNA and TNF- α expression and enhanced islet cell renewal, insulin, and immunoreactivities.ConclusionInflammatory indicators are elevated in the presence of T2DM. Extract of EA has overall tissue reparative and safeguarding properties, as indicated by the augmented β- cell population and enhanced glucose homeostasis. Thus, EA may be an innovative treatment approach for the maintenance of normoglycemia in individuals with T2DM. 相似文献
8.
Robert Mason Helen C. Dearden Bella Nguyen Jennifer A. Soon Jessica Louise Smith Manreet Randhawa Andrew Mant Lydai Warburton Serigne Lo Tarek Meniawy Alexander Guminski Phillip Parente Sayed Ali Andrew Haydon Georgina V. Long Matteo S. Carlino Michael Millward Victoria G. Atkinson Alexander M. Menzies 《Pigment cell & melanoma research》2020,33(2):358-365
The combination of ipilimumab and nivolumab is a highly active systemic therapy for metastatic melanoma but can cause significant toxicity. We explore the safety and efficacy of this treatment in routine clinical practice, particularly in the setting of serine/threonine‐protein kinase B‐Raf (BRAF)‐targeted therapy. Consecutive patients with unresectable stage IIIC/IV melanoma commenced on ipilimumab and nivolumab across 10 tertiary melanoma institutions in Australia were identified retrospectively. Data collected included demographics, response and survival outcomes. A total of 152 patients were included for analysis, 39% were treatment‐naïve and 22% failed first‐line BRAF/MEK inhibitors. Treatment‐related adverse events occurred in 67% of patients, grade 3–5 in 38%. The overall objective response rate was 41%, 57% in treatment‐naïve and 21% in BRAF/MEK failure patients. Median progression‐free survival was 4.0 months (95% CI, 3.0–6.0) in the whole cohort, 11.0 months (95% CI, 6.0‐NR) in treatment‐naïve and 2.0 months (95% CI, 1.4–4.6) in BRAF/MEK failure patients. The combination of ipilimumab and nivolumab can be used safely and effectively in a real‐world population. While first‐line efficacy appears comparable to trial populations, BRAF‐mutant patients failing prior BRAF/MEK inhibitors show less response. 相似文献
9.
Alex Zaufel Sandra M.W. van de Wiel Lu Yin Günter Fauler Daphne Chien Xinzhong Dong John F. Gilmer Jennifer K. Truong Paul A. Dawson Stan F.J. van de Graaf Peter Fickert Tarek Moustafa 《生物化学与生物物理学报:疾病的分子基础》2021,1867(8):166153
IsoBAs, stereoisomers of primary and secondary BAs, are found in feces and plasma of human individuals. BA signaling via the nuclear receptor FXR is crucial for regulation of hepatic and intestinal physiology/pathophysiology. Aim: Investigate the ability of BA-stereoisomers to bind and modulate FXR under physiological/pathological conditions. Methods: Expression-profiling, luciferase-assays, fluorescence-based coactivator-association assays, administration of (iso)-BAs to WT and cholestatic mice. Results: Compared to CDCA/isoCDCA, administration of DCA/isoDCA, UDCA/isoUDCA only slightly increased mRNA expression of FXR target genes; the induction was more evident looking at pre-mRNAs. Notably, almost 50% of isoBAs were metabolized to 3-oxo-BAs within 4 h in cell-based assays, making it difficult to study their actions. FRET-based real-time monitoring of FXR activity revealed that isoCDCA>CDCA stimulated FXR, and isoDCA and isoUDCA allowed fully activated FXR to be re-stimulated by a second dose of GW4064. In vivo co-administration of a single dose of isoBAs followed by GW4064 cooperatively activated FXR, as did feeding of UDCA in a background of endogenous FXR ligands. However, in animals with biliary obstruction and concomitant loss of intestinal BAs, UDCA was unable to increase intestinal Fgf15. In contrast, mice with an impaired enterohepatic circulation of BAs (Asbt?/?, Ostα?/?), administration of UDCA was still able to induce ileal Fgf15 and repress hepatic BA-synthesis, arguing that UDCA is only effective in the presence of endogenous FXR ligands. Conclusion: Secondary (iso)BAs cooperatively activate FXR in the presence of endogenous BAs, which is important to consider in diseases linked to disturbances in BA enterohepatic cycling. 相似文献
10.
Tarek S. Ibrahim Amr H. Moustafa Ahmad J. Almalki Rasha M. Allam Abdulhamid Althagafi Shadab Md Mamdouh F. A. Mohamed 《Journal of enzyme inhibition and medicinal chemistry》2021,36(1):1067
Two series of chalcone/aryl carboximidamide hybrids 4a–f and 6a–f were synthesised and evaluated for their inhibitory activity against iNOS and PGE2. The most potent derivatives were further checked for their in vivo anti-inflammatory activity utilising carrageenan-induced rat paw oedema model. Compounds 4c, 4d, 6c and 6d were proved to be the most effective inhibitors of PGE2, LPS-induced NO production, iNOS activity. Moreover, 4c, 4d, 6c and 6d showed significant oedema inhibition ranging from 62.21% to 78.51%, compared to indomethacin (56.27 ± 2.14%) and celecoxib (12.32%). Additionally, 4c, 6a and 6e displayed good COX2 inhibitory activity while 4c, 6a and 6c exhibited the highest 5LOX inhibitory activity. Compounds 4c, 4d, 6c and 6d fit nicely into the pocket of iNOS protein (PDB ID: 1r35) via the important amino acid residues. Prediction of physicochemical parameters exhibited that 4c, 4d, 6c and 6d had acceptable physicochemical parameters and drug-likeness. The results indicated that chalcone/aryl carboximidamides 4c, 4d, 6c and 6d, in particular 4d and 6d, could be used as promising lead candidates as potent anti-inflammatory agents. 相似文献