High efficacy of tamoxifen-loaded L-lysine coated magnetic iron oxide nanoparticles in cell cycle arrest and anti-cancer activity for breast cancer therapy.

Introduction: Due to the side effects of drugs, the development of nanoscale drug delivery systems has led to a significant improvement in medicinal therapies due to drug pharmacokinetics changes, decreased toxicity, and increased half-life of the drug. This study aimed to synthesize tamoxifen (TMX)-loaded L-lysine coated magnetic iron oxide nanoparticles as a nano-carrier to investigate its cytotoxic effects and anti-cancer properties against MCF-7 cancer cells. Methods: Magnetic Fe3O4 nanoparticles were synthesized and coated with L-lysine (F-Lys NPs). Then, TMX was loaded onto these NPs. The characteristics of synthesized nanoparticles (F-Lys-TMX NPs) were evaluated by X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), transmission electron microscopy (TEM), dynamic light scattering (DLS), differential scanning calorimetry (DSC), vibrating sample magnetometer (VSM), and thermogravimetric analysis (TGA). The drug release was analyzed at pH 5.8 and pH 7.4. The MCF-7 cells were exposed to F-Lys-TMX NPs, F-Lys NPs, and TMX for 24, 48, and 72 hours. To evaluate the cytotoxic potential of designed nanoparticles, MTT and apoptosis assays, real-time PCR, and cell cycle analysis was carried out. Results: The F-Lys-TMX NPs had spherical morphology with a size ranging from 9 to 30 nm. By increasing the nanoparticles concentration and treatment time, more cell proliferation inhibition and apoptosis induction were observed in F-Lys-TMX NPs-treated cells compared to the TMX. The expression levels of ERBB2, cyclin D1, and cyclin E genes were down-regulated and expression levels of the caspase-3 and caspase-9 genes were up-regulated. Studies on the drug release revealed a slow and controlled pH-dependent release of the nanoparticles. Cell cycle analysis indicated that F-Lys-TMX NPs could arrest the cells at the G0/G1 phase. Conclusion: The findings suggest that F-Lys-TMX NPs are more effective and have the potential for cell proliferation inhibition and apoptosis induction compared to the TMX. Hence, F-Lys-TMX NPs can be considered as an anti-cancer agent against MCF-7 breast cancer cells.

Comparison of the effects of etomidate, ketamine, sodium thiopental, and midazolam on the mortality of patients with COVID-19 requiring intubation.

Background: Among the medications administered for the management of COVID-19 patients, the induction drugs used for intubation have received little attention. The aim of this study was to compare the effect of induction drugs on the mortality of patients with COVID-19 requiring intubation. Methods: In this retrospective study, all patients who were admitted to Shahid Sadoughi and Shahid Rahnemoun hospitals in Yazd from February to March 2020 with definitive diagnosis of COVID-19 and needed intubation were enrolled. Patients were divided into 4 groups based on the type of drugs used in intubation, and mortality rate was assessed at the end of the first, second, fourth, and seventh days of the study. Statistical analyses were performed using SPSS 20 and P values <.05 was considered significant. Results: In this study, 76 patients were examined. Patients were divided into 4 groups, of which 21 were in etomidate group, 8 in ketamine group, 21 in sodium thiopental group, and 35 in midazolam group. Mortality rate in these 4 groups was 25%, 12.5%, 14.3%, and 14.3% (p=0.822), respectively at the end of the first day after intubation; it was 83.3%, 12.5%, 28.6%, and 25.7% (p=0.001), respectively, at the end of the second day; it was 83.3%, 12.5%, 42.9%, and 42.9% (p=0.015), respectively, until the end of the fourth day; it was 100%, 25%, 61.9%, and 65.7% (p=0.007), respectively, until the end of the seventh day. Admission to intubation time interval was 0.91±0.99, 3.12±1.95, 4.09±2.44, and 4.74±2.62 days, respectively (p<0.001). Conclusion: The results of this study suggest that the use of etomidate may be associated with higher mortality in COVID-19 patients. Further studies are needed to verify the results of this study.

Brainstem Correlates of Comodulation Masking Release for Speech in Normal Hearing Adults.

BACKGROUND AND OBJECTIVES: Weak signals embedded in fluctuating masker can be perceived more efficiently than similar signals embedded in unmodulated masker. This release from masking is known as comodulation masking release (CMR). In this paper, we investigate, neural correlates of CMR in the human auditory brainstem. SUBJECTS AND METHODS: A total of 26 normal hearing subjects aged 18-30 years participated in this study. First, the impact of CMR was quantified by a behavioral experiment. After that, the brainstem correlates of CMR was investigated by the auditory brainstem response to complex sounds (cABR) in comodulated (CM) and unmodulated (UM) masking conditions. RESULTS: The auditory brainstem responses are less susceptible to degradation in response to the speech syllable /da/ in the CM noise masker in comparison with the UM noise masker. In the CM noise masker, frequency-following response (FFR) and fundamental frequency (F0) were correlated with better behavioral CMR. Furthermore, the subcortical response timing of subjects with higher CMR was less affected by the CM noise masker, having higher stimulus-to-noise response correlations over the FFR range. CONCLUSIONS: The results of the present study revealed a significant link between brainstem auditory processes and CMR. The findings of the present study show that cABR provides objective information about the neural correlates of CMR for speech stimulus.

Musical Training Enhances Neural Processing of Comodulation Masking Release in the Auditory Brainstem.

Musical training strengthens segregation the target signal from background noise. Musicians have enhanced stream segregation, which can be considered a process similar to comodulation masking release. In the current study, we surveyed psychoacoustical comodulation masking release in musicians and non-musicians. We then recorded the brainstem responses to complex stimuli in comodulated and unmodulated maskers to investigate the effect of musical training on the neural representation of comodulation masking release for the first time. The musicians showed significantly greater amplitudes and earlier brainstem response timing for stimulus in the presence of comodulated maskers than non-musicians. In agreement with the results of psychoacoustical experiment, musicians showed greater comodulation masking release than non-musicians. These results reveal a physiological explanation for behavioral enhancement of comodulation masking release and stream segregation in musicians.