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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.
Fatemeh Davodabadi Shekoufeh Mirinejad Sonia Fathi-Karkan Mahdi Majidpour Narges Ajalli Roghayeh Sheervalilou Saman Sargazi Dominika Rozmus Abbas Rahdar Ana M. Diez-Pascual 《Biotechnology progress》2023,39(5):e3366
Aptamers (Apts) are synthetic nucleic acid ligands that can be engineered to target various molecules, including amino acids, proteins, and pharmaceuticals. Through a series of adsorption, recovery, and amplification steps, Apts are extracted from combinatorial libraries of synthesized nucleic acids. Using aptasensors in bioanalysis and biomedicine can be improved by combining them with nanomaterials. Moreover, Apt-associated nanomaterials, including liposomes, polymeric, dendrimers, carbon nanomaterials, silica, nanorods, magnetic NPs, and quantum dots (QDs), have been widely used as promising nanotools in biomedicine. Following surface modifications and conjugation with appropriate functional groups, these nanomaterials can be successfully used in aptasensing. Advanced biological assays can use Apts immobilized on QD surfaces through physical interaction and chemical bonding. Accordingly, modern QD aptasensing platforms rely on interactions between QDs, Apts, and targets to detect them. QD-Apt conjugates can be used to directly detect prostate, ovarian, colorectal, and lung cancers or simultaneously detect biomarkers associated with these malignancies. Tenascin-C, mucin 1, prostate-specific antigen, prostate-specific membrane antigen, nucleolin, growth factors, and exosomes are among the cancer biomarkers that can be sensitively detected using such bioconjugates. Furthermore, Apt-conjugated QDs have shown great potential for controlling bacterial infections such as Bacillus thuringiensis, Pseudomonas aeruginosa, Escherichia coli, Acinetobacter baumannii, Campylobacter jejuni, Staphylococcus aureus, and Salmonella typhimurium. This comprehensive review discusses recent advancements in the design of QD-Apt bioconjugates and their applications in cancer and bacterial theranostics. 相似文献
3.
The effectiveness of posterior annuloplasty in two patients who failed to respond to medical treatment for atrial and ventricular arrhythmias related to mitral valve prolapse (MVP) is reported. Although the etiology of arrhythmia in MVP remains mostly speculative, anatomic correction of prolapse or billowing of the mitral leaflets appears to reverse the anatomic and pathologic conditions that cause the arrhythmia. 相似文献
4.
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
5.
P Paucek G Mironova F Mahdi A D Beavis G Woldegiorgis K D Garlid 《The Journal of biological chemistry》1992,267(36):26062-26069
The transport properties of mitochondria are such that net potassium flux across the inner membrane determines mitochondrial volume. It has been known that K+ uptake is mediated by diffusive leak driven by the high electrical membrane potential maintained by redox-driven, electrogenic proton ejection and that regulated K+ efflux is mediated by an 82-kDa inner membrane K+/H+ antiporter. There is also long-standing suggestive evidence for the existence of an inner membrane protein designed to catalyze electrophoretic K+ uptake into mitochondria. We report reconstitution of a highly purified inner membrane protein fraction from rat liver and beef heart mitochondria that catalyzes electrophoretic K+ flux in liposomes and channel activity in planar lipid bilayers. The unit conductance of the channel at saturating [K+] is about 30 pS. Reconstituted K+ flux is inhibited with high affinity by ATP and ADP in the presence of divalent cations and by glibenclamide in the absence of divalent cations. The mitochondrial ATP-dependent K+ channel is selective for K+, with a Km of 32 mM, and does not transport Na+. K+ transport depends on voltage in a manner consistent with a channel activity that is not voltage-regulated. Thus, the mitochondrial ATP-dependent K+ channel exhibits properties that are remarkably similar to those of the ATP-dependent K+ channels of plasma membranes. 相似文献
6.
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
7.
Dastmalchi Narges Safaralizadeh Reza Hosseinpourfeizi Mohammad Ali Baradaran Behzad Khojasteh Seyed Mahdi Banan 《Molecular biology reports》2021,48(2):1345-1357
Molecular Biology Reports - Combination therapy has been considered as a potential method to overcome the BC chemoresistance. MicroRNAs (miRs) have been suggested as a therapeutic factor in the... 相似文献
8.
Saremi Leila Shafizadeh Marziyeh Esmaeilzadeh Emran Ghaffari Mohammad Ebrahim Mahdavi Mohammad hosein Amid Reza Kadkhodazadeh Mahdi 《Molecular biology reports》2021,48(3):2285-2290
Molecular Biology Reports - Peri-implantitis (PI) is a multifactorial condition caused by the interactions of pathogens and the host immune response. Previous studies have demonstrated a... 相似文献
9.
Yadav Jyoti Verma Anoop Kumar Ahmad Md. Kaleem Garg Ravindra K. Shiuli Mahdi Abbas Ali Srivastava Shrikant 《Molecular biology reports》2021,48(4):3245-3252
Molecular Biology Reports - Alzheimer's disease is a common neurodegenerative disease in the elderly population and a leading cause of dementia. Genetics and environmental risk factors were... 相似文献
10.
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