Zinc Protoporphyrin Polymeric Nanoparticles: Potent Heme Oxygenase Inhibitor for Cancer Therapy

Purpose

Oxidation therapy is an antitumor strategy in which, apoptosis or necrosis is caused by either excess delivery of reactive oxygen species (ROS) as an oxidant or anti-oxidant inhibition. Heme oxygenase (HO) is an anti-oxidant enzyme that plays an important role in cell growth and proliferation. The purpose of this study was to prepare poly lactic-co-glycolic acid (PLGA) nanoparticles (NPs) loaded with zinc protoporphyrin (ZnPP) to deliver the HO inhibitor into tumor.

Methods

PLGA NPs were prepared using nanoprecipitation technique and their characteristics were optimized by Box-Behnken experimental design. Scanning electron microscopy and in vitro studies consisting of drug release, HO inhibitory effect, cytotoxicity and cellular uptake followed by in vivo biodistribution and blood cytotoxicity were carried out. Internalization of coumerin-6 loaded NPs by PC3 cells was visualized by confocal laser scanning microscopy beside quantitatively analysis.

Results

NPs average size, entrapment efficiency and drug loading were 100.12?±?5.345 nm, 55.6%?±?2.49 and 7.98%?±?0.341 respectively. Equal HO inhibitory effect of NPs compared to free ZnPP was observed. The IC₅₀ value of ZnPP-NPs for PC3 human prostate cancer cells was found to be 2.14?±?0.083 μM.

Conclusion

In conclusion, ZnPP loaded PLGA NPs could exhibit enough HO inhibitory effect against cancer cells to be considered as a promising candidate for cancer treatment investigation.     

Evaluation of Alum-Naltrexone Adjuvant Activity,on Efficacy of Anti-Leishmania Immunization with Autoclaved Leishmania major (MRHO/IR/75/ER) Antigens in BALB/C Mice

Background

Naltrexone, an opioid receptor antagonist shifts the immune response toward a Th1 profile. In the current study, we evaluated the efficacy of the mixture of NTX and alum, as a new adjuvant, to enhance immune response and induce protection against Leishmania major in a mouse model.

Methods

BALB/c mice were immunized three times either autoclaved L. major promastigotes’ antigens alone or in combination with the adjuvant alum, naltrexone or the alum–naltrexone mixture. Both humoral and cellular immune responses were assessed two weeks after the last immunization and compared with control mice.

Results

The administration of alum- NTX in combination with the parasite antigen, significantly increased production of IFN-γ IFN-γ /IL-5 ratio, lymphocyte proliferation and improved DTH response against L. major. There was no significant difference in survival following challenge among groups.

Conclusion

Immunization with the alum– naltrexone mixture as an adjuvant, in combination with the autoclaved L. major promastigotes antigens, can enhance cellular immunity and shift the immune responses to a Th1 pattern.     

Statistical Evaluation of the Material-Source Effects on the DSR Rheological Properties of Plant-Mix Extracted Asphalt-Binders

The work presented in this paper was carried out to statistically evaluate and quantify the material-source effect on the asphalt-binder’s rheological properties using Analysis of Variance (ANOVA) and Tukey’s Honestly Significant Difference (Tukey´s HSD) test. The study focused on the Asphalt-Binders’ high-temperature rheological properties, namely, the G*, δ, G*/Sin(δ) and G*/(1 − (1/Tan(δ)Sin(δ))) parameters, measured using the Dynamic Shear Rheometer (DSR) device. The DSR data analyzed in the study were extracted from the Texas flexible pavements and overlays database, namely, the Texas Data Storage System (DSS), covering two Asphalt-Binders (ABs), performance grade (PG) 64-22 and PG 76-22 plant-mix extracted ABs that were treated as rolling thin film oven (RTFO) residue, and sourced from 14 different suppliers. The study findings substantiate that material-source has an effect on the high-temperature rheological properties of ABs. Additionally, it was also concluded that in as much as performance superiority and costs are crucial issues in deciding the AB source/provider, consistency and quality aspects cannot be disregarded. Therefore, material-source effects should be inclusively evaluated from both performance (rheological properties) and quality (consistence) standpoints as well as cost considerations when choosing a supplier. In general, the study contributes to the state-of-the-art enrichment on aspects of material-source effects on RTFO residue ABs’ high-temperature rheological properties, consistency, variability, and data quality.     

Structure-Function Analyses of New SARS-CoV-2 Variants B.1.1.7, B.1.351 and B.1.1.28.1: Clinical,Diagnostic, Therapeutic and Public Health Implications

SARS-CoV-2 (Severe Acute Respiratory Syndrome-Coronavirus 2) has accumulated multiple mutations during its global circulation. Recently, three SARS-CoV-2 lineages, B.1.1.7 (501Y.V1), B.1.351 (501Y.V2) and B.1.1.28.1 (P.1), have emerged in the United Kingdom, South Africa and Brazil, respectively. Here, we have presented global viewpoint on implications of emerging SARS-CoV-2 variants based on structural–function impact of crucial mutations occurring in its spike (S), ORF8 and nucleocapsid (N) proteins. While the N501Y mutation was observed in all three lineages, the 501Y.V1 and P.1 accumulated a different set of mutations in the S protein. The missense mutational effects were predicted through a COVID-19 dedicated resource followed by atomistic molecular dynamics simulations. Current findings indicate that some mutations in the S protein might lead to higher affinity with host receptors and resistance against antibodies, but not all are due to different antibody binding (epitope) regions. Mutations may, however, result in diagnostic tests failures and possible interference with binding of newly identified anti-viral candidates against SARS-CoV-2, likely necessitating roll out of recurring “flu-like shots” annually for tackling COVID-19. The functional relevance of these mutations has been described in terms of modulation of host tropism, antibody resistance, diagnostic sensitivity and therapeutic candidates. Besides global economic losses, post-vaccine reinfections with emerging variants can have significant clinical, therapeutic and public health impacts.     

Association between sleep duration and sleep quality with sugar and sugar-sweetened beverages intake among university students

Background and aim

Both short sleep duration and intake of sugar or sugar-sweetened beverages (SSBs) are associated with weight gain; but the linkage between sleep characteristics and sugar or SSBs intake was less studied. We aimed to evaluate the associations of sleep duration and sleep quality with sugar and SSBs intake among Iranian adults.

Method

This cross-sectional study consisted of 395 adults chosen among students of Isfahan University of Medical Sciences, based on a multistage cluster random sampling method. Sleep characteristics and dietary intakes and were assessed using the Pittsburgh Sleep Quality Index (PSQI) and a 147-item validated food frequency questionnaire, respectively.

Results

Mean age and percentage of women in the study population were 22.79 (year) and 51.8%, respectively. No significant difference was observed between sleep duration and sugar intake, but short sleepers (< 6 h/d) had higher consumption of SSBs intake (86.54 vs. 65.73 g/day; P = 0.05) in comparison with those who had more than 8 h/d of sleep. Poor quality sleepers had significantly higher intake of SSBs compared with those with good quality of sleeping (87.09 vs. 56.73 g/day; P = 0.004). No significant correlation was found between sleep duration and SSBs intake. However, sleep quality score was positively correlated with SSBs intake (r_p:0.14, P = 0.007) in whole population, such that higher quality score (defined as poor sleep quality) was correlated with greater consumption of SSBs. Similar results were found in younger individuals (r_p:0.27, P = 0.002) and non-obese participants (r_p:0.14, P = 0.006).

Conclusion

We found that sleep duration was not associated with sugar or SSBs intake in Iranian adults. Poor sleep quality was correlated with high consumption of SSBs, especially in younger and non-obese individuals. More prospective investigations are required to confirm these findings.

     

A Novel Protocol to Differentiate Induced Pluripotent Stem Cells by Neuronal microRNAs to Provide a Suitable Cellular Model

Neurodegenerative diseases are one of the most challenging subjects in medicine. Investigation of their underlying genetic or epigenetic factors is hampered by lack of suitable models. Patient‐specific induced pluripotent stem cells (iPS cells) represent a valuable approach to provide a proper model for poorly understood mechanisms of neuronal diseases and the related drug screenings. miR‐124 and miR‐128 are the two brain‐enriched miRNAs with different time‐points of expression during neuronal development. Herein, we transduced human iPS cells with miR‐124 and miR‐128 harboring lentiviruses sequentially. The transduced plasmids contained GFP and puromycin antibiotic‐resistant genes for easier selection and identification. Morphological assessment and immunocytochemistry (overexpressions of beta‐tubulin and neuron‐specific enolase) confirmed that induced hiPS cells by miR‐124 and miR‐128 represent similar characteristics to those of mature neurons. In addition, the upregulation of neuron‐specific enolase, beta‐tubulin, Map2, GFAP, and BDNF was detected by quantitative real‐time PCR. In conclusion, it seems that our novel protocol remarks the combinatorial effect of miR‐124 and miR‐128 on neural differentiation in the absence of any extrinsic factor. Moreover, such cellular models could be used in personalized drug screening and applied for more effective therapies.