The arylidene indanone scaffold has contributed many lead molecules in chemotherapeutic anticancer agent research.
To determine the oxidant-scavenging activities and antiproliferative activity of (2E)-2-benzylidene-4,7-dimethyl-2,3-dihydro-1H-inden-1-one (MLT-401), an arylidene indanone derivative.
Jurkat cells, primary lymphocytes, and Vero cells were treated with MLT-401. Antioxidant properties of MLT-401 were determined using 2,2-diphenyl-1-picrylhydrazyl (DPPH)-based, 2,2′-azino-bis-(3-ethylbenzothiazoline-6-sulphonic acid) diammonium salt (ABTS)-based, and ferric-reducing antioxidant potential (FRAP) assays. Inhibition of cell proliferation was determined using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide-based assay. Nuclear status was determined using a DNA fragmentation assay, and cell cycle stage was analyzed by flow cytometry. Mitochondrial membrane enzyme activities were measured using colorimetric methods.
The antioxidant assays gave MLT-401 half maximal inhibitory concentration (IC50) values of 1611 nM (DPPH-based assay), 2115 nM (ABTS-based assay), and 1586 nM (FRAP assay). MLT-401 inhibited proliferation of Jurkat cells with a concentration for 50% of maximal inhibition of cell proliferation (GI50) of 341.5 nM, being 12- and 9-fold less than GI50 concentrations for normal lymphocytes and Vero cells, respectively. MLT-401 caused nuclear fragmentation and DNA laddering as seen by electrophoresis. Jurkat cells showed a time-dependent accumulation of sub G0/G1 cells after MLT-401 treatment. Mitochondrial membrane-bound Na+/K+ ATPase, Ca2+ ATPase, and Mg2+ ATPase activities were inhibited by MLT-401 in a dose-dependent manner.
MLT-401 possesses significant antiproliferative activity and scavenges free radicals released through mitochondrial membrane damage in a Jurkat cell line model of cancer cells. Further investigation of MLT-401 as a chemotherapeutic anticancer agent and development of other arylidene indanone analogues are warranted. A detailed elucidation of mechanistic pathways is required for further development.
Serum starvation is mostly considered as a standard preparatory method in many cellular and molecular experiments. However, recent studies give some evidence that serum starvation is a major event that triggers various cell responses and has therefore great potential to change and interfere with the experimental results. In this study, the behavior of breast cancer cells in serum-starved condition was examined.
To focus on the role of serum starvation on cell migration and also the possible changes in the expression and secretion of genes and cytokines mostly involved in migration and chemotaxis of breast cancer cells.
MDA-MB-231 cells were cultured under serum-starved condition. Transwell migration assay was performed to evaluate the effect of serum starvation on cell migration after 24, 48, and 72 h. The transcriptional expression of migration-related genes was evaluated using real-time polymerase chain reaction. The cytokine secretion was also analyzed using enzyme-linked immunosorbent assay.
Serum starvation suppressed cell migration in breast cancer cells. Additionally, the gene expression of markers involved in migration including β-catenin, twist, zinc finger E-box binding homeobox 1, vimentin, fibronectin, intercellular adhesion molecule 1, and vascular endothelial growth factor were downregulated. Moreover, cytokines of transforming growth factor, beta 1, matrix metallopeptidase 9, interleukin 8, and nitric oxide were differentially secreted.
Serum deprivation causes significant changes in cancer cell migration and also the expression of migration-related genes and cytokines, special care needs to be taken when this practice is used as preparatory method especially in migration and chemotaxis experiments on cancer cells.
Multidrug-resistant bacteria are becoming more hazardous day by day for human health all over the world, and the scientific community is trying hard to resolve this issue by various approaches. One of the very common approaches is to bind drugs to nanoparticles and study enhanced antibacterial properties.
To compare simultaneously different types of nanoparticles, their concentration, bacterial strains and their incubation time intervals for each of the selected drug combination.
We have selected the most commonly used gold and silver nanoparticles and few examples from fluoroquinolone antibiotics to make their conjugates and study their efficacy against multidrug-resistant E. coli and S. aureus strains simultaneously, at different incubation time intervals and different concentration of nanoparticles.
Gold nanoparticle hybrids do not show any significant effect. Silver nanoparticle hybrids show far better results, even at extremely low concentrations.
This unique and simple approach allows us to know the exact time intervals and concentration required for each nanoparticle combination to control the growth for any specific strain. This approach can be extended to any set of nanoparticles, drugs and bacterial strains for comparative purposes.
Simulation is widely used in airway management training.
To show that assigning anesthesia residents’ simulation educator roles improved cognitive learning outcomes.
Postgraduate second- and third-year (PGY-2 and PGY-3) anesthesia residents were randomly assigned to three groups: a teacher group (T), a hot-seat (active participant) group (H), and an observer group (O). After a train-the-trainer session, the T group prepared simulation scenarios for difficult airway management and then conducted the simulation sessions and post-session debriefing. The H group participated in the scenarios, and the O group observed the sessions. All participants attended the post-session debriefing. Evaluation was conducted at pretest, immediate posttest, and 3 months (retention test). Score differentiation and average normalized gain were calculated. Participants completed a post-simulation class survey.
Participants were 49 residents (PGY-2 = 24, PGY-3 = 25). The T group had the highest posttest score (17.06 ± 1.23); this score significantly differed from the O group (14.75 ± 2.57, P = 0.003) but not the H group (15.64 ± 1.54, P = 0.103). The average normalized gain was significantly higher in the T group than in the H and O groups (0.51 ± 0.22, 0.18 ± 0.32, and 0.17 ± 0.47, respectively; P = 0.012). Participants retained knowledge at 3 months after the session, with no significant differences among the groups. Most participants (45%) preferred to be active scenario participants, and 20% preferred to teach. Overall satisfaction was high in all groups.
This study showed that a teaching role can be effectively applied for residents in simulation-based education on difficult airway management to support better learning outcomes.
Acute liver failure (ALF) is a rare condition during neonatal period.
To report a case of recipient twin with fulminant ALF secondary to hydrops fetalis caused by twin-to-twin transfusion syndrome (TTTS).
The patient was admitted to the neonatal intensive care unit (NICU) for respiratory failure requiring mechanical ventilation and fulminant ALF with prolonged international normalized ratio (INR) and elevated liver enzymes with highest aspartate aminotransferase of 4,580 U/L.
Laboratory investigation for secondary causes of liver failure was not revealing. Her liver enzymes and coagulation levels were dramatically normalized as the clinical symptoms of hypervolemia improved within 1 week.
TTTS can be a possible cause of neonatal ALF. Early detection with proper management of TTTS is important to avoid adverse outcomes. However, pathogenesis of hepatic dysfunction in TTTS is rarely described, and further studies are needed to help understanding the correlation between liver diseases and TTTS.
Practical domestic monitoring of the menstrual cycle requires measurements of urinary metabolites of reproductive hormones: oestrone glucuronide (E1G) and pregnanediol glucuronide (PdG). Data reported in the literature are expressed as (i) concentration, without or with either creatinine- or specific gravity correction, or (ii) excretion rates. This variation in such a fundamental issue prompts consideration of the relationships between the four measures. Because the menstrual cycle kinetics of E1G and PdG are complex, we consider measurements of urinary creatinine, urea, galactose, xylose and inulin which tend to be more stable. We show that uncorrected concentration measurements of these urinary analytes can be positively correlated, negatively correlated or uncorrelated with the serum concentration. Based on measurements of urinary creatinine concentrations, urinary specific gravity and creatinine excretion rates, we conclude that urinary analyte concentration are likely to be more reliable when creatinine-corrected rather than corrected using specific gravity, but that both are less reliable than measurements of the excretion rate. This has implications for the quantitation of any urinary analyte, but especially for the monitoring of the menstrual cycle in which changes in E1G and PdG from one day to the next can be physiologically significant for a woman monitoring her fertility.