Anti-cancer characteristics of mevinolin against three different solid tumor cell lines was not solely p53-dependent

Mevinolin (MVN) has been used clinically for the treatment of hypercholesterolemia with very good tolerance by patients. Based on epidemiological evidences, MVN was suggested strongly for the treatment of neoplasia. Early experimental trials suggested the mixed apoptotic/necrotic cell death pathway was activated in response to MVN exposure. Herein, the cytotoxic profile of MVN was evaluated, compared to the robust and frequently used anti-cancer drug doxorubicin (DOX), against breast (MCF-7), cervical (HeLa) and liver (HepG(2)) transformed cell lines. MVN was showed comparable results in cytotoxic profile with DOX in all tested solid tumor cell lines. In addition, the MVN-induced cytotoxicity was inferred to be multi-factorial and not solely dependent on p53 expression. It was concluded that molecular and genetic assessment of MVN-induced cell death would be useful for developing cancer therapeutic treatments.     

Multi-spectroscopic,thermodynamic and molecular docking studies to investigate the interaction of eplerenone with human serum albumin

The binding of small molecular drugs with human serum albumin (HSA) has a crucial influence on their pharmacokinetics. The binding interaction between the antihypertensive eplerenone (EPL) and HSA was investigated using multi-spectroscopic techniques for the first time. These techniques include ultraviolet-visible (UV-vis) spectroscopy, Fourier-transform infrared (FTIR), native fluorescence spectroscopy, synchronous fluorescence spectroscopy and molecular docking approach. The fluorescence spectroscopic study showed that EPL quenched HSA inherent fluorescence. The mechanism for quenching of HSA by EPL has been determined to be static in nature and confirmed by UV absorption and fluorescence spectroscopy. The modified Stern–Volmer equation was used to estimate the binding constant (K_b) as well as the number of bindings (n). The results indicated that the binding occurs at a single site (K_b = 2.238 × 10³ L mol⁻¹at 298 K). The enthalpy and entropy changes (∆H and ∆S) were 58.061 and 0.258 K J mol⁻¹, respectively, illustrating that the principal intermolecular interactions stabilizing the EPL–HSA system are hydrophobic forces. Synchronous fluorescence spectroscopy revealed that EPL binding to HSA occurred around the tyrosine (Tyr) residue and this agreed with the molecular docking study. The Förster resonance energy transfer (FRET) analysis confirmed the static quenching mechanism. The esterase enzyme activity of HSA was also evaluated showing its decrease in the presence of EPL. Furthermore, docking analysis and site-specific markers experiment revealed that EPL binds with HSA at subdomain IB (site III).     

Cytopathology of extramedullary plasmacytoma of the bladder: a case report

BACKGROUND: Plasmacytoma of the bladder is an extremely rare tumor, with all information concerning this neoplasm derived from case reports. It can be a major diagnostic pitfall on both histology and urine cytology. CASE: A 95-year-old woman presented with gross hematuria and a large bladder mass detected by ultrasound. The case was initially misdiagnosed as a high grade urothelial carcinoma. Since the urine cytology did not show the classical cytologic features of urothelial carcinoma, the histologic sections were reviewed and immunohistochemical staining performed. The final diagnosis was plasmacytoma of the bladder. Subsequently the patient underwent a skeletal survey and bone scan, which did not reveal any lesion suspicious for multiple myeloma. The patient was scheduled for radiotherapy. CONCLUSION: In this case of bladder plasmacytoma, urine cytology provided a clue to the diagnosis. Urine cytology can be a diagnostic tool to help make this diagnosis in the case of poorly differentiated bladder neoplasm, especially in a patient with a known history of multiple myeloma.     

Atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion: cytohistologic correlation study with diagnostic pitfalls

OBJECTIVE: In the current study, we explore the diagnostic parameters and pitfalls in the follow-up of 123 cases of Pap smears diagnosed as high-grade atypical squamous cells (ASC-H) at our institution. STUDY DESIGN: A computer database search was performed from the archives of the Ottawa Hospital Cytopathology Service for cases diagnosed with ASC-H between January 2003 and July 2005. RESULTS: Follow-up of the 123 cases of ASC-H showed high grade squamous intraepithelial lesion (HSIL) in 73 patients (59.4%), low grade squamous intraepithelial lesion (LSIL) in 11 (8.9%), immature squamous metaplasia in 23 (18.7%), reactive squamous cell changes in 12 (9.8%), benign glandular lesions (endocervical atypia, degenerated glandular cells) in 2 (1.6%) and atrophy in 2 (1.6%). In our study, 83 patients were younger than 40 years (67.4%), with biopsy-proven HSIL found in 54 patients (65.1%). The remaining 40 patients (32.6%) were older than 40 years of age, and follow-up biopsies showed HSIL in 19 patients (47.5%). CONCLUSION: In our study, 59.4% of the cases that were diagnosed cytologically as ASC-H were found to have HSIL on subsequent biopsies. This correlation was stronger in patients below the age of 40 years (65.1% vs. 47.5%). The cytopathologic feature most strongly associated with HSIL was the presence of coarse nuclear chromatin (84%).     

Molecular evolution of chloroplast DNA in fig (Ficus carica L.): Footprints of sweep selection and recent expansion

Here, we report the nucleotide variation in two non-coding regions of the chloroplast DNA (cpDNA) to construct a possible evolutionary scenario in Ficus carica L. Our results suggest the occurrence of haplotypic and nucleotide diversity with a large variation level of chloroplast non-coding regions. Furthermore, our results demonstrated an explicit rejection of the null hypothesis that within F. carica the intron trnL and the spacer trnL-trnF evolved under a strictly neutral model of molecular evolution. Although, recent population expansion could serve as one alternative explanation for the detected excess of singleton, our results imply a positive selection and the genetic hitchhiking effect is unlikely. Parameters performed supported scenario of sweep selection and recent expansion of F. carica across Tunisia. Our results indicate that both positive selection and demographic histories have jointly contributed to the observed patterns of nucleotide diversity and haplotypes structure. Based on the results, we characterize the fig resources and provide several suggestions for effective conservation and improvement programs.     

Microbial diversity in Tunisian geothermal springs as detected by molecular and culture-based approaches

Prokaryotic diversities of 12 geothermal hot springs located in Northern, Central and Southern Tunisia were investigated by culture-based and molecular approaches. Enrichment cultures for both aerobic and anaerobic microorganisms were successfully obtained at temperatures ranging from 50 to 75°C. Fourteen strains including four novel species were cultivated and assigned to the phyla Firmicutes (9), Thermotogae (2), Betaproteobacteria (1), Synergistetes (1) and Bacteroidetes (1). Archaeal or universal oligonucleotide primer sets were used to generate 16S rRNA gene libraries. Representative groups included Proteobacteria, Firmicutes, Deinococcus-Thermus, Thermotogae, Synergistetes, Bacteroidetes, Aquificae, Chloroflexi, candidate division OP9 in addition to other yet unclassified strains. The archaeal library showed a low diversity of clone sequences belonging to the phyla Euryarchaeota and Crenarchaeota. Furthermore, we confirmed the occurrence of sulfate reducers and methanogens by amplification and sequencing of dissimilatory sulfite reductase (dsrAB) and methyl coenzyme M reductase α-subunit (mcrA) genes. Altogether, we discuss the diverse prokaryotic communities arising from the 12 geothermal hot springs studied and relate these findings to the physico-chemical features of the hot springs.     

A global mathematical model of the cerebral circulation in man

A mathematical model of the cerebral circulation has been formulated. It was based on non-linear equations of pulsatile fluid flow in distensible conduits and applied to a network simulating the entire cerebral vasculature, from the carotid and vertebral arteries to the sinuses and the jugular veins. The quasilinear hyperbolic system of equations was numerically solved using the two-step Lax-Wendroff scheme. The model's results were in good agreement with pressure and flow data recorded in humans during rest. The model was also applied to the study of autoregulation during arterial hypotension. A close relationship between cerebral blood flow (CBF) and capillary pressure was obtained. At arterial pressure of 80 mmHg, the vasodilation of the pial arteries was unable to maintain CBF at its control value. At the lower limit of autoregulation (60 mm Hg), CBF was maintained with a 25% increase of zero transmural pressure diameter of nearly the whole arterial network.     

Effects of NaCl or Na<Subscript>2</Subscript>SO<Subscript>4</Subscript> salinity on plant growth,ion content and photosynthetic activity in <Emphasis Type="Italic">Ocimum basilicum</Emphasis> L.

Basil (Ocimum basilicum L., cultivar Genovese) plants were grown in Hoagland solution with or without 50 mM NaCl or 25 mM Na₂SO₄. After 15 days of treatment, Na₂SO₄ slowed growth of plants as indicated by root, stem and leaf dry weight, root length, shoot height and leaf area, and the effects were major of those induced by NaCl. Photosynthetic response was decreased more by chloride salinity than by sulphate. No effects in both treatments on leaf chlorophyll content, maximal efficiency of PSII photochemistry (F _v/F _m) and electron transport rate (ETR) were recorded. Therefore, an excess of energy following the limitation to CO₂ photoassimilation and a down regulation of PSII photochemistry was monitored under NaCl, which displays mechanisms that play a role in avoiding PSII photodamage able to dissipate this excess energy. Ionic composition (Na⁺, K⁺, Ca²⁺, and Mg²⁺) was affected to the same extent under both types of salinity, thus together with an increase in leaves Cl⁻, and roots SO₄ ²⁻ in NaCl and Na₂SO₄-treated plants, respectively, may have resulted in the observed growth retardation (for Na₂SO₄ treatment) and photosynthesis activity inhibition (for NaCl treatment), suggesting that those effects seem to have been due to the anionic component of the salts.