Insights of Platinum Drug Interaction with Spinel Magnetic Nanocomposites for Targeted Anti-Cancer Effect.

In nanotherapeutics, gaining insight about the drug interaction with the pore architecture and surface functional groups of nanocarriers is crucial to aid in the development of targeted drug delivery. Manganese ferrite impregnated graphene oxide (MnFe2O4/GO) with a two-dimensional sheet and spherical silica with a three-dimensional interconnected porous structure (MnFe2O4/silica) were evaluated for cisplatin release and cytotoxic effects. Characterization studies revealed the presence of Mn2+ species with a variable spinel cubic phase and superparamagnetic effect. We used first principles calculations to study the physisorption of cisplatin on monodispersed silica and on single- and multi-layered GO. The binding energy of cisplatin on silica and single-layer GO was ~1.5 eV, while it was about double that value for the multilayer GO structure. Moreover, we treated MCF-7 (breast cancer cells) and HFF-1 (human foreskin fibroblast) with our nanocomposites and used the cell viability assay MTT. Both nanocomposites significantly reduced the cell viability. Pt4+ species of cisplatin on the spinel ferrite/silica nanocomposite had a better effect on the cytotoxic capability when compared to GO. The EC50 for MnFe2O4/silica/cisplatin and MnFe2O4/GO/cisplatin on MCF-7 was: 48.43 µg/mL and 85.36 µg/mL, respectively. The EC50 for the same conditions on HFF was: 102.92 µg/mL and 102.21 µg/mL, respectively. In addition, immunofluorescence images using c-caspase 3/7, and TEM analysis indicated that treating cells with these nanocomposites resulted in apoptosis as the major mechanism of cell death.

Varied Composition and Underlying Mechanisms of Gut Microbiome in Neuroinflammation.

The human gut microbiome has been implicated in a host of bodily functions and their regulation, including brain development and cognition. Neuroinflammation is a relatively newer piece of the puzzle and is implicated in the pathogenesis of many neurological disorders. The microbiome of the gut may alter the inflammatory signaling inside the brain through the secretion of short-chain fatty acids, controlling the availability of amino acid tryptophan and altering vagal activation. Studies in Korea and elsewhere highlight a strong link between microbiome dynamics and neurocognitive states, including personality. For these reasons, re-establishing microbial flora of the gut looks critical for keeping neuroinflammation from putting the whole system aflame through probiotics and allotransplantation of the fecal microbiome. However, the numerosity of the microbiome remains a challenge. For this purpose, it is suggested that wherever possible, a fecal microbial auto-transplant may prove more effective. This review summarizes the current knowledge about the role of the microbiome in neuroinflammation and the various mechanism involved in this process. As an example, we have also discussed the autism spectrum disorder and the implication of neuroinflammation and microbiome in its pathogenesis.

Exome array identifies functional exonic biomarkers for pediatric dental caries.

BACKGROUND: Pediatric dental caries is common among Arab children, however we are still searching for possible genes and molecular mechanisms that influence caries development. AIM: To identity genetic predispositions of dental caries among Saudi children with high DMFT (Decayed, Missing, and Filled Teeth). DESIGN: This case-control study analysed putative functional exonic-variants (n = 243,345) to study the molecular genetics of pediatric caries with high dmft index, 8.75 ± 4.16 on Arab-ancestry subjects with primary dentition (n = 111; 76 cases, dmft>5 and 35 controls, dmft = 0). RESULTS: Pediatric caries is significantly associated with single nucleotide polymorphisms (SNP) in the GRIN2B-rs4764039C (p-value = 2.03 × 10-08) and CFH-rs1065489G (p-value = 8.26 × 10-08) genes, even after Bonferroni correction. Irregular tooth brushing habits (p = 0.0404) and irregular dental visits (p = 0.0050) are significantly associated with caries. Functional enrichment analysis of significant genes is associated with calcium-activated chloride channel, Staphylococcus aureus infection, and N-linked glycosylation. CONCLUSION: Genetic predispositions are found to be significantly associated with the high prevalence of pediatric caries, which is a disorder of multigene-environment interaction. The significant functional exonic variants identified can be biomarkers for the early diagnosis of pediatric dental caries in Arabs.

Bibliometric analysis of Neurosciences research productivity in Saudi Arabia from 2013-2018.

OBJECTIVE: To review the dynamics of neuroscience research in the Kingdom of Saudi Arabia (KSA) from 2013-2018. METHODS: Subject category of Neuroscience was selected in the SciVal feature of Scopus database, which includes all relevant categories of the field limiting it to Saudi Arabia. RESULTS: Saudi Arabia is ranked 39th in publishing neuroscientific research worldwide. The number of yearly published articles has increased from 123 to 332 during the time period between 2013 and 2018. King Saud University & King Abdul Aziz University & their corresponding regions namely Western and Central regions are the major contributors to publications. Neuroscientists working in Saudi Arabia have collaboration with scientists from all over the world. The top 10 preferred journals are all international. In subcategories of neuroscience, developmental neuroscience seems the one that needs attention. CONCLUSION: Neuroscience research is on the rise in KSA. Older and well-established institutions like King Saud University & King Abdul Aziz University have taken lead in publishing neuroscientific research. International collaboration in all subfields of neuroscience is substantial. Eastern Southern and Northern regions and developmental neuroscience require more focus and funding.

Quantum dots encapsulated with curcumin inhibit the growth of colon cancer, breast cancer and bacterial cells.

Aim: To synthesize and examine the impact of free Eudragit® RS 100 nanoparticles (LN01), Quantum dots curcumin-loaded Eudragit RS 100 nanoparticles (LN04), and un-encapsulated curcumin nanoparticles (LN06) on cancerous and bacterial cells. Materials & methods: The LN01, LN04, LN06 were synthesized and characterized by Fourier transform infrared, ζ potential, UV-Vis spectroscopy, transmission electron microscopy and scanning electron microscopy and their biological activities were evaluated. Results: LN04 profoundly inhibited the growth of colon (HCT-116) cancerous cells (10.64% cell viability) and breast cancer (MCF-7) cells (10.32% cell viability) with compared to LN01 and LN06. Normal cells (HEK-293) did not show any inhibition after treatments. In addition, LN04 show better inhibitory action on bacterial growth compared with LN01 and LN06. Conclusion: We suggest that LN04 selectively target cancerous and bacterial cells and therefore possess potential anticancer and antibacterial capabilities.

Targeted therapeutic effect against the breast cancer cell line MCF-7 with a CuFe2O4/silica/cisplatin nanocomposite formulation.

The combination of magnetic nanoparticles with a porous silica is a composite that has attracted significant attention for potential multifunctional theranostic applications. In this study, 30 wt % CuFe2O4 was impregnated into a matrix of monodispersed spherical hydrophilic silica (HYPS) nanoparticles through a simple dry impregnation technique. The chemotherapy drug cisplatin was loaded through electrostatic equilibrium adsorption over 24 h in normal saline solution. The presence of cubic spinel CuFe2O4 on HYPS was confirmed through powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FTIR) and diffuse reflectance UV-vis spectroscopy (DR UV-vis) analysis. The HYPS particles showed a surface area of 170 m2/g, pore size of 8.3 nm and pore volume of 0.35 cm3/g. The cisplatin/CuFe2O4/HYPS nanoformulation showed the accumulation of copper ferrite nanoparticles on the surface and in the pores of HYPS with a surface area of 45 m2/g, pore size of 16 nm and pore volume of 0.18 cm3/g. Transmission electron microscopy (TEM) and energy dispersive X-ray (EDX) mapping analysis showed the presence of homogeneous silica particles with nanoclusters of copper ferrite distributed on the HYPS support. Vibrating sample magnetometry (VSM) analysis of CuFe2O4/HYPS showed paramagnetic behavior with a saturated magnetization value of 7.65 emu/g. DRS UV-vis analysis revealed the functionalization of cisplatin in tetrahedral and octahedral coordination in the CuFe2O4/HYPS composite. Compared to other supports such as mesocellular foam and silicalite, the release of cisplatin using the dialysis membrane technique was found to be superior when CuFe2O4/HYPS was applied as the support. An in vitro experiment was conducted to determine the potential of CuFe2O4/HYPS as an anticancer agent against the human breast cancer cell line MCF-7. The results show that the nanoparticle formulation can effectively target cancerous cells and could be an effective tumor imaging guide and drug delivery system.

Functional DNA variations associated with Saudi female with low VO2max: a pilot microarray study.

The study aims to explore the genetic predispositions and molecular pathways of low cardiorespiratory fitness (VO2max) in young Saudi females (n = 70). Young females were grouped based on the level of VO2max according to the specification of the physical fitness specialist certification as low VO2max (< 28.9; n = 19) and high VO2max (> 33; n = 14) and genotyped for 243345 putative functional exonic variants. The CYFIP2&FNDC9-rs10037485T, C1R-rs75380747G and TOP2A-rs13695C SNPs on chromosome 5, 12 and 17, respectively were found to be the most significant among young Saudi females with low VO2max (P < 8.01 × 10-05). Linkage disequilibrium (LD) analysis among the significant SNPs (P < 0.001) have revealed risk and protective haplotypes with high degree (p-value < 1.0 × 10-4) of LD. The most significant risk haplotypes with the low VO2max in young Saudi females are: Chromosome 1: LOC112268276-rs10800201G; LOC112268276-rs4657537A; rs4657583T (p-value = 2.00 × 10-04); Chromosome 3: rs978979G; CCDC66-rs7637449A; CCDC66-rs111934125T; FAM208A-rs9835332G (p-value = 5.00 × 10-04) and Chromosome 17: STX2-rs13696C; TNS4-rs1901187C (p-value = 1.00 × 10-04). Functional Enrichment Analysis revealed that the genes with SNPs P < 0.001 have significantly involved in the heart rate (P = 0.00442), body weight (P = 0.00629), breath tests (P = 0.0147), proteolysis (P = 0.00623) and cardiac muscle fiber development (P = 0.0263). In conclusion we could say that the identified genetic predispositions and gene-annotation enrichment in low VO2max in young Saudi females revealed that they are at high risk for developing cardiovascular complications.

Exposure to early life adversity alters the future behavioral response to a stressful challenge in BALB/C mice.

Depression is considered as a maladaptive response to stress in adult life. Exposure to stress in early childhood is recognized as a risk factor for being unable to adapt to environmental changes in adult life. Early life stress (ELS) has been modelled in animals to help understand the behavioral outcome of the adversity. Periodic maternal separation (MS) in rodents for the first two weeks of life is one such model. We used MS as a form of ELS in Balb/c mice to study its effect on a stressful challenge encountered in adult life. According to our results, exposure to MS predisposed mice to an altered behavioral response. However, this response was not worsened by exposure to restraint stress (RS) experienced in early adult life. This controversy may be attributed to methodological and biological variations among animals as well as humans.

A simplified colorimetric method for rapid detection of cell viability and toxicity in adherent cell culture systems.

PURPOSE: Evaluation of cell viability and toxicity in adherent culture systems is of critical relevance for a wide range of disciplines of biomedical sciences research, including cancer research, toxicology, pharmacology, cell biology, neurology and nanomedicine. Several well-established cytotoxicity assays are widely used by researchers, including the most-preferred MTT assay. Nevertheless, there are problems associated with them, for example; in terms of the time-factor and solubilization of the formzan crystals before its spectroscopic quantification. In this study, we propose a simple, fast and cost-effective colorimetric assay that is free of these issues. METHODS: Our assay was based upon reductive splitting of blue-green colored supravital safranin derivative dye Janus green B (JG-B) to pink colored diethyl safranin by oxidoreductases of the electron transport chain (ETC) of actively respiring mitochondria. Because this conversion can be easily and reliably followed spectroscopically, measure of diethyl safranin formed from extraneously added JG-B provides a proficient indicator of cellular health and viability. RESULTS: Using MCF-7, a breast cancer cell line, we provide a proof of concept for the suggested assay and compare it with the MTT assay. CONCLUSION: Unlike the MTT assay, our JG-B assay does not require a solubilization/extraction step, and hence follows a much simpler and time-efficient protocol suitable for high-throughput analysis of cell viability in anchorage-dependent cell culture models. Additionally, the JG-B cell viability assay reported here can be suitably applied either independently or in complementation with other assays for the analysis of cellular viability and toxicity in both analytic and therapeutic aspects of research.

Simple, reliable, and time-efficient colorimetric method for the assessment of mitochondrial function and toxicity.

Mitochondria are organelles involved in the production of cellular energy, regulation of Ca2+ and redox signaling, and are critical for normal functioning of eukaryotic cells. The dysfunction of mitochondria has been implicated in a wide range of diseases, including metabolic and neurodegenerative disorders and different types of cancers. To better understand the role of mitochondria in healthy and disease states, the development of efficient and reliable tools for the assessment of mitochondrial function is particularly important. Janus green B (JG-B) is a supravital lipophilic cationic dye which, in its oxidized form, has a green-blue color. As JG-B is taken up and reduced by metabolically active mitochondria, the dye has been used for assessing the purity, integrity and metabolic activity of mitochondria with microscopy-based methods. Here we present a simple, time- and cost-efficient JG-B-based colorimetric assay for assessing mitochondrial function, activity and toxicity. The method is based upon reduction of JG-B by mitochondrial dehydrogenases to diethylsafranine, which is pink colored and has a maximum absorption at 550 nm. In this proof of principle study, using in vitro mitochondrial preparations isolated from rat brain, we provide evidence that monitoring JG-B conversion to diethylsafranine can be used as a reliable and robust indicator of mitochondrial activity and toxicity. Because of its simplicity and efficiency in terms of costs and time, this assay has a wide potential in analytical as well as therapeutic areas of biomedical research.

Dysfunction of cortical synapse-specific mitochondria in developing rats exposed to lead and its amelioration by ascorbate supplementation.

BACKGROUND: Lead (Pb) is a widespread environmental neurotoxin and its exposure even in minute quantities can lead to compromised neuronal functions. A developing brain is particularly vulnerable to Pb mediated toxicity and early-life exposure leads to permanent alterations in brain development and neuronal signaling and plasticity, culminating into cognitive and behavioral dysfunctions and elevated risk of neuropsychiatric disorders later in life. Nevertheless, the underlying biochemical mechanisms have not been completely discerned. METHODS: Because of their ability to fulfill high energy needs and to act as calcium buffers in events of high intensity neuronal activity as well as their adaptive regulatory capability to match the requirements of the dynamicity of synaptic signaling, synapse-specific or synaptic mitochondria (SM) are critical for synaptic development, function and plasticity. Our aim for the present study hence was to characterize the effects of early-life Pb exposure on the functions of SM of prepubertal rats. For this purpose, employing a chronic model of Pb neurotoxicity, we exposed rat pups perinatally and postnatally to Pb and used a plethora of colorimetric and fluorometric assays for assessing redox and bioenergetic properties of SM. In addition, taking advantage of its ability as an antioxidant and as a metal chelator, we employed ascorbic acid (vitamin C) supplementation as an ameliorative therapeutic strategy against Pb-induced neurotoxicity and dysfunction of SM. RESULTS: Our results suggest that early-life exposure to Pb leads to elevated oxidative stress in cortical SM with consequent compromises in its energy metabolism activity. Ascorbate supplementation resulted in significant recovery of Pb-induced oxidative stress and functional compromise of SM. CONCLUSION: Alterations in redox status and bioenergetic properties of SM could potentially contribute to the synaptic dysfunction observed in events of Pb neurotoxicity. Additionally, our study provides evidence for suitability of ascorbate as a significant ameliorative agent in tacking Pb neurotoxicity.