Modulatory effects of miRNAs in doxorubicin resistance: A mechanistic view.

MicroRNAs (miRNAs) are a group of small non-coding RNAs and play an important role in controlling vital biological processes, including cell cycle control, apoptosis, metabolism, and development and differentiation, which lead to various diseases such as neurological, metabolic disorders, and cancer. Chemotherapy consider as gold treatment approaches for cancer patients. However, chemotherapeutic is one of the main challenges in cancer management. Doxorubicin (DOX) is an anti-cancer drug that interferes with the growth and spread of cancer cells. DOX is used to treat various types of cancer, including breast, nervous tissue, bladder, stomach, ovary, thyroid, lung, bone, muscle, joint and soft tissue cancers. Also recently, miRNAs have been identified as master regulators of specific genes responsible for the mechanisms that initiate chemical resistance. miRNAs have a regulatory effect on chemotherapy resistance through the regulation of apoptosis process. Also, the effect of miRNAs p53 gene as a key tumor suppressor was confirmed via studies. miRNAs can affect main biological pathways include PI3K pathway. This review aimed to present the current understanding of the mechanisms and effects of miRNAs on apoptosis, p53 and PTEN/PI3K/Akt signaling pathway related to DOX resistance.

Flexible surface acoustic wave technology for enhancing transdermal drug delivery.

Transdermal drug delivery provides therapeutic benefits over enteric or injection delivery because its transdermal routes provide more consistent concentrations of drug and avoid issues of drugs affecting kidneys and liver functions. Many technologies have been evaluated to enhance drug delivery through the relatively impervious epidermal layer of the skin. However, precise delivery of large hydrophilic molecules is still a great challenge even though microneedles or other energized (such as electrical, thermal, or ultrasonic) patches have been used, which are often difficult to be integrated into small wearable devices. This study developed a flexible surface acoustic wave (SAW) patch platform to facilitate transdermal delivery of macromolecules with fluorescein isothiocyanates up to 2000 kDa. Two surrogates of human skin were used to evaluate SAW based energized devices, i.e., delivering dextran through agarose gels and across stratum corneum of pig skin into the epidermis. Results showed that the 2000 kDa fluorescent molecules have been delivered up to 1.1 mm in agarose gel, and the fluorescent molecules from 4 to 2000 kDa have been delivered up to 100 µm and 25 µm in porcine skin tissue, respectively. Mechanical agitation, localised streaming, and acousto-thermal effect generated on the skin surface were identified as the main mechanisms for promoting drug transdermal transportation, although micro/nanoscale acoustic cavitation induced by SAWs could also have its contribution. SAW enhanced transdermal drug delivery is dependent on the combined effects of wave frequency and intensity, duration of applied acoustic waves, temperature, and drug molecules molecular weights.

Predictive factors for COVID-19 severity and mortality in hospitalized children.

BACKGROUND: Understanding the factors influencing disease progression and severity in pediatric COVID-19 cases is essential for effective management and intervention strategies. This study aimed to evaluate the discriminative ability of clinical and laboratory parameters to identify predictors of COVID-19 severity and mortality in hospitalized children. METHODS: In this multicenter retrospective cohort study, we included 468 pediatric patients with COVID-19. We developed a predictive model using their demographic, clinical, and laboratory data. The performance of the model was assessed using various metrics including sensitivity, specificity, positive predictive value rates, and receiver operating characteristics (ROC). RESULTS: Our findings demonstrated strong discriminatory power, with an area under the curve (AUC) of 0.818 for severity and 0.873 for mortality prediction. Key risk factors for severe COVID-19 in children include low albumin levels, elevated C-reactive protein (CRP), lactate dehydrogenase (LDH), and underlying medical conditions. Furthermore, ROC curve analysis highlights the predictive value of CRP, LDH, and albumin, with AUC values of 0.789, 0.752, and 0.758, respectively. CONCLUSION: Our study indicates that laboratory values are valuable in predicting COVID-19 severity in children. Various factors, including CRP, LDH, and albumin levels, demonstrated statistically significant differences between patient groups, suggesting their potential as predictive markers for disease severity. Implementing predictive analyses based on these markers could aid clinicians in making informed decisions regarding patient management.

MicroRNAs targeted mTOR as therapeutic agents to improve radiotherapy outcome.

MicroRNAs (miRNAs) are small RNA molecules that regulate genes and are involved in various biological processes, including cancer development. Researchers have been exploring the potential of miRNAs as therapeutic agents in cancer treatment. Specifically, targeting the mammalian target of the rapamycin (mTOR) pathway with miRNAs has shown promise in improving the effectiveness of radiotherapy (RT), a common cancer treatment. This review provides an overview of the current understanding of miRNAs targeting mTOR as therapeutic agents to enhance RT outcomes in cancer patients. It emphasizes the importance of understanding the specific miRNAs that target mTOR and their impact on radiosensitivity for personalized cancer treatment approaches. The review also discusses the role of mTOR in cell homeostasis, cell proliferation, and immune response, as well as its association with oncogenesis. It highlights the different ways in which miRNAs can potentially affect the mTOR pathway and their implications in immune-related diseases. Preclinical findings suggest that combining mTOR modulators with RT can inhibit tumor growth through anti-angiogenic and anti-vascular effects, but further research and clinical trials are needed to validate the efficacy and safety of using miRNAs targeting mTOR as therapeutic agents in combination with RT. Overall, this review provides a comprehensive understanding of the potential of miRNAs targeting mTOR to enhance RT efficacy in cancer treatment and emphasizes the need for further research to translate these findings into improved clinical outcomes.

Volatile oil constituents, antioxidant and antibacterial activities of Lonicera caprifolium L. in different areas of Iran.

The genus of Lonicera is the largest genus of Caprifoliaceae family. This study revealed the composition, antioxidant, and antibacterial actions of essential oils of Lonicera caprifolium L. in different areas of Iran; Qom, Mashhad, Shiraz. Gas chromatography-mass spectrometry examination was applied to recognise the oil conformation. The essential oils of Qom included a high number of monoterpenes, with linalool as the significant constituent. In the essential oil of Mashhad, the main elements were methyl linoleate. The essential oil of Shiraz displayed a similar profile, including a large quantity of fatty acid, with methyl palmitate as the main component. The antioxidant activity was assessed via the DPPH exam, and the antimicrobial action was verified using the broth microdilution procedure. The essential oils of Qom revealed the maximum antimicrobial and antioxidant actions between the three regions, ascribed to its high concentration of monoterpenes and phenolic composites. Moreover, principal component analysis (PCA) and heat map successfully revealed the variation and correlation between metabolites of the three oils. These conclusions highlight the potential of L. caprifolium as natural foundations of antimicrobial and antioxidant representatives, with investigation required to reveal their therapeutic requests.

Determination of heavy metals in edible oils by a novel voltammetry taste sensor array.

Herein, a novel voltammetry taste sensor array (VTSA) using pencil graphite electrode, screen-printed electrode, and glassy carbon electrode was used to identify heavy metals (HM) including Cad, Pb, Sn and Ni in soybean and rapeseed oils. HMs were added to edible oils at three concentrations of 0.05, 0.1 and 0.25 ppm, and then, the output of the device was classified using a chemometric classification method. According to the principal component analysis results, PG electrode explains 96% and 81% of the variance between the data in rapeseed and soybean edible oils, respectively. Additionally, the SP electrode explains 91% of the variance between the data in rapeseed and soybean oils. Moreover, the GC electrode explains 100% and 99% of the variance between the data in rapeseed and soybean edible oils, respectively. K-nearest neighbor exhibited high capability in classifying HMs in edible oils. In addition, partial least squares in the combine of VTSA shows a predict 99% in rapeseed oil. The best electrode for soybean edible oil was GC.

Mitochondria-loaded alginate-based hydrogel accelerated angiogenesis in a rat model of acute myocardial infarction.

Here, mitochondria were isolated from mesenchymal stem cells (MSCs) after being treated with mitochondria-stimulating substrates, 50 µM metformin (Met), and 40 µM dichloroacetic acid (DCA). The isolated mitochondria (2 × 107 particles) were characterized and encapsulated inside 100 µl hydrogel composed of alginate (3 % w/v; Alg)/gelatin (Gel; 1 % w/v) enriched with 1 µM pyrrole (Pyr) solidified in the presence of 0.2 M FeCl3. The physicochemical properties and cytocompatibility of prepared hydrogels were assessed using FTIR, swelling, biodegradation, porosity assays, and scanning electron microscopy (SEM). The mitochondria-bearing hydrogel was injected into the ischemic area of rat hearts. FTIR absorption bands represented that the addition of FeCl3 led to polypyrrole (PPy) formation, polysaccharide oxidation, and interaction between Alg and Gel. SEM images exhibited porous structure and the size of pores was reduced in Alg/Gel + PPy group compared to Alg + PPy hydrogel. Based on the data, both Alg + PPy and Alg/Gel + PPy hydrogels can preserve the integrity and morphology of loaded mitochondria. It was noted that Alg/Gel + PPy hydrogel possessed a higher swelling ratio, degradation, and porosity compared to Alg + PPy group. Data confirmed that Alg/Gel + PPy hydrogel containing 1 µM Pyr yielded the highest survival rate compared to groups with 2 and 4 µM Pyr (p < 0.05). Injection of mitochondria-loaded Alg/Gel + PPy hydrogel yielded significant restoration of left ventricle thickness compared to the infarction, mitochondria, and Alg/Gel + PPy hydrogel groups 14 days post-injection (p < 0.05). Histological analyses revealed a significant increase of vWF+ capillaries and α-SMA+ arterioles in the mitochondria-loaded Alg/Gel + PPy hydrogel group (p < 0.05). Immunofluorescence imaging revealed the ability of rat cardiomyocytes to uptake mitochondria alone or after being loaded into Alg/Gel + PPy hydrogel. These effects were evident in the Alg/Gel + PPy group. Taken together, electroconductive Alg-based hydrogels are suitable platforms for the transplantation of cells and organelles and the regeneration of ischemic heart changes.

Fundamentals of Monitoring Condensation and Frost/Ice Formation in Cold Environments Using Thin-Film Surface-Acoustic-Wave Technology.

Moisture condensation, fogging, and frost or ice formation on structural surfaces cause severe hazards in many industrial components such as aircraft wings, electric power lines, and wind-turbine blades. Surface-acoustic-wave (SAW) technology, which is based on generating and monitoring acoustic waves propagating along structural surfaces, is one of the most promising techniques for monitoring, predicting, and also eliminating these hazards occurring on these surfaces in a cold environment. Monitoring condensation and frost/ice formation using SAW devices is challenging in practical scenarios including sleet, snow, cold rain, strong wind, and low pressure, and such a detection in various ambient conditions can be complex and requires consideration of various key influencing factors. Herein, the influences of various individual factors such as temperature, humidity, and water vapor pressure, as well as combined or multienvironmental dynamic factors, are investigated, all of which lead to either adsorption of water molecules, condensation, and/or frost/ice in a cold environment on the SAW devices. The influences of these parameters on the frequency shifts of the resonant SAW devices are systematically analyzed. Complemented with experimental studies and data from the literature, relationships among the frequency shifts and changes of temperature and other key factors influencing the dynamic phase transitions of water vapor on SAW devices are investigated to provide important guidance for icing detection and monitoring.

Monitoring of crack healing in geopolymer concrete using a nonlinear ultrasound approach in phase-space domain.

Ultrasonic testing is a robust non-destructive evaluation method frequently employed in the health monitoring of concrete structures. Cracking in concrete can be one of the most critical problems, and its healing is important for structural safety. The current study proposes the evaluation of crack healing in geopolymer concrete (GPC) using different linear and nonlinear ultrasonic techniques. In this regard, a notched GPC beam was constructed at the laboratory and geopolymer grout was applied as a repair material. Ultrasonic pulse velocity (UPV) and signal waveform tests were performed at several stages before and after grouting the notch. Nonlinear wave signals were processed in the phase-space domain for qualitative health monitoring of GPC. Furthermore, feature extraction was applied to phase-plane attractors using fractal dimension for quantitative assessment. The sideband peak count-index (SPC-I) method was also utilized to assess the ultrasound waves. The results indicate that the phase-space analysis of ultrasound can successfully represent the healing progress inside the GPC beam. At the same time, the fractal dimension can be used as a healing index. Ultrasound signal attenuation demonstrated high sensitivity to crack healing. The SPC-I technique exhibited an inconsistent trend at the early stage of healing. However, it provided a clear indication of repair at the advanced stage. Although the linear UPV method was found sensitive to the grouting at the initial stages, it demonstrated insufficient capability to monitor the healing process fully. Therefore, the phase-space-based ultrasonic method and the attenuation parameter could be employed as reliable techniques for the robust monitoring of progressive healing in concrete.

VEGFR2 Mimicking Peptide Inhibits the Proliferation of Human Umbilical Vein Endothelial Cells (Huvecs) by Blocking VEGF.

INTRODUCTION: A variety of key human physiological processes rely on angiogenesis, ranging from reproduction and fetal growth to wound healing and tissue repair. Furthermore, this process significantly contributes to tumor progression, invasion, and metastasis. As the strongest inducer of angiogenesis, Vascular Endothelial Growth Factor (VEGF) and its receptor (VEGFR) are targets of therapeutic research for blocking pathological angiogenesis. OBJECTIVE: Preventing the interaction between VEGF and VEGFR2 by a peptide is a promising strategy for developing antiangiogenic drug candidates. This study was aimed at designing and evaluating VEGF-targeting peptides using in silico and in vitro techniques. METHODS: The VEGF binding site of VEGFR2 was considered a basis for peptide design. The interaction of VEGF and all three peptides derived from VEGFR2 were analyzed using ClusPro tools. In a complex with VEGF, the peptide with a higher docking score was evaluated to confirm its stability using molecular dynamics (MD) simulation. The gene coding for the selected peptide was cloned and expressed in E. coli BL21. The bacterial cells were cultured on a large scale, and the expressed recombinant peptide was purified using Ni-NTA chromatography. Refolding of the denatured peptide was carried out by the stepwise removal of the denaturant. The reactivity of peptides was confirmed using western blotting and enzyme-linked immunosorbent assay (ELISA) assays. Finally, the inhibition potency of the peptide on human umbilical vein endothelial cells was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl- 2H-tetrazolium bromide (MTT) assay. RESULTS: Among three peptides, the peptide with the best docking pose and the highest affinity for VEGF was selected for further studies. Then the stability of the peptide was confirmed over the 100 ns MD simulation. After in silico analyses, the selected peptide was presented for in vitro analysis. Expression of the selected peptide in E. coli BL21 resulted in a pure peptide with a yield of approximately 200 µg/ml. Analysis by ELISA revealed the high reactivity of the peptide with VEGF. Western blot analysis confirmed the specific reactivity of selected peptides with VEGF. The MTT assay revealed the growth inhibitory effect of the peptide on human umbilical vein endothelial cells with an IC50 value of 247.8 µM. CONCLUSION: In summary, the selected peptide demonstrated a promising inhibitory effect on human umbilical vein endothelial cells that could be a valuable anti-angiogenic candidate for further assessment. Additionally, these in silico and in vitro data provide new insights into peptide design and engineering.

Current Status and Challenges of Vaccination Therapy for Glioblastoma.

Glioblastoma (GBM), also known as grade IV astrocytoma, is the most common and deadly type of central nervous system malignancy in adults. Despite significant breakthroughs in current GBM treatments such as surgery, radiotherapy, and chemotherapy, the prognosis for late-stage glioblastoma remains bleak due to tumor recurrence following surgical resection. The poor prognosis highlights the evident and pressing need for more efficient and targeted treatment. Vaccination has successfully treated patients with advanced colorectal and lung cancer. Therefore, the potential value of using tumor vaccines in treating glioblastoma is increasingly discussed as a monotherapy or in combination with other cellular immunotherapies. Cancer vaccination includes both passive administration of monoclonal antibodies and active vaccination procedures to activate, boost, or bias antitumor immunity against cancer cells. This article focuses on active immunotherapy with peptide, genetic (DNA, mRNA), and cell-based vaccines in treating GBM and reviews the various treatment approaches currently being tested. Although the ease of synthesis, relative safety, and ability to elicit tumor-specific immune responses have made these vaccines an invaluable tool for cancer treatment, more extensive cohort studies and better guidelines are needed to improve the efficacy of these vaccines in anti-GBM therapy.

RNA interference: Promising approach for breast cancer diagnosis and treatment.

Today, cancer is one of the main health-related challenges, and in the meantime, breast cancer (BC) is one of the most common cancers among women, with an alarming number of incidences and deaths every year. For this reason, the discovery of novel and more effective approaches for the diagnosis, treatment, and monitoring of the disease are very important. In this regard, scientists are looking for diagnostic molecules to achieve the above-mentioned goals with higher accuracy and specificity. RNA interference (RNAi) is a posttranslational regulatory process mediated by microRNA intervention and small interfering RNAs. After transcription and edition, these two noncoding RNAs are integrated and activated with the RNA-induced silencing complex (RISC) and AGO2 to connect the target mRNA by their complementary sequence and suppress their translation, thus reducing the expression of their target genes. These two RNAi categories show different patterns in different BC types and stages compared to healthy cells, and hence, these molecules have high diagnostic, monitoring, and therapeutic potentials. This article aims to review the RNAi pathway and diagnostic and therapeutic potentials with a special focus on BC.

Clinical characteristics and outcomes of the multisystem inflammatory syndrome in children (MIS-C) following COVID-19 infection in Iran: A multicenter study.

OBJECTIVES: This study aimed to assess the clinical characteristics, treatment and outcomes of the multisystem inflammatory syndrome in children (MIS-C) following COVID-19 in five different geographical regions of Iran. METHODS: In this multicenter observational study, patients <21 years were included between March 2020 and October 2021. By Disease Control and Prevention (CDC) checklist, demographic characteristics, comorbidities, clinical signs and symptoms, laboratory and radiology findings, and treatment were collected. Statistical analysis was using Chi-square and t-test in STATA14. RESULTS: In total 225 patients with median age of 55 (26-96) months were included that 59.56% boys. 57.33% were admitted to the PICU with a median of 7 days (4-10). 95.56% of patients were discharged with recovery and the rest died. All of the patients in our study were included based on the MIS-C criteria. However, some patients had Kawasaki symptoms, so we compared the clinical and epidemiological characteristics of the two groups. Conjunctival injection, cervical lymphadenopathy>1.5 cm diameter, and strawberry tongue in Kawasaki-like MIS-C patients were higher than of MIS-C patients, and this difference was significant(p<0.001). The most common comorbidity was obesity (24.86%). Most patients tested for COVID-19 and about 60% of the patients had a positive test by serology or reverse transcription-polymerase chain reaction (RT-PCR). Gastrointestinal (88.89%) and hematologic signs (84.44%) were most common. Most drugs used in patients were IVIG and steroids. 88.07% and 61.29% of the patients had at least one problem in echocardiography and lung CT, respectively. CONCLUSIONS: The best outcome was seen in patients who were treated with both IVIG and steroids on the first days of admission. Myocarditis was common in two groups of patients. According to most patients had echocardiography abnormal, screening of heart function is recommended for patients.

Evidence-Based Prediction of COVID-19 Severity in Hospitalized Children.

Objective: In this study, by using clinical and paraclinical characteristics, we have aimed to predict the severity of the disease in hospitalized COVID-19 children. Method: This cross-sectional study was conducted on medical records about epidemiologic data, underlying diseases, symptoms, and laboratory tests from March to October, 2020, on 238 hospitalized confirmed COVID-19 paediatric cases in several children's hospitals of Tehran, Ahwaz, Isfahan, and Bandar Abbas. Results: From 238 patients, 140 (59%) were male and most of them were in the age group of 1 to 5 years (34.6%). Among all hospitalized patients, 38% had an underlying disease and in total, 5% of cases were expired. Conclusion: Determining patient severity is essential for appropriate clinical decision making; our results showed that in hospitalized pediatric patients, by using several variables such as SGOT, CRP, ALC, LDH, WBC, O2sat, and ferritin, we can use clinical and paraclinical characteristics for predicting the severity of COVID-19.

Sensitive and convenient detection of miRNA-145 using a gold nanoparticle-HCR coupled system: computational and in vitro validations.

Multiple sclerosis (MS) remains a challenging disease that requires timely diagnosis. Therefore, an ultrasensitive optical biosensor based on hybridization chain reaction (HCR) was developed to detect microRNA-145 (miRNA-145) as an MS biomarker. To construct such a sensor, HCR occurred between specific hairpin probes, as MB1 contains a poly-cytosine nucleotide loop and MB2 has a poly-guanine nucleotide sticky end. By introducing miR-145 as a target sequence, long-range dsDNA polymers are formed. Then, positively charged gold nanoparticles (AuNPs) were incubated with the HCR product, which adsorbed onto the dsDNA polymers due to electrostatic adsorption. This resulted in the precipitation of the AuNPs. By incubating different concentrations of miR-145 with AuNPs, the changes in the UV-vis spectrum of the supernatant were analyzed. The proposed biosensor showed a great ability to detect miR-145 in a wide linear range from 1 pM-1 nM with an excellent detection limit (LOD) of 0.519 nM. Furthermore, the developed biosensor indicated considerable selectivity in discriminating between miR-145 and mismatched sequences. It shows high selectivity in differentiating targets. Interestingly, the proposed method was also able to detect miRNA-145 in the diluted serum samples. In conclusion, this sensing platform exhibits high selectivity and specificity for the detection of circulating microRNAs, which holds great promise for translation to routine clinical applications.

Node formation mechanisms in acoustofluidic capillary bridges.

Using acoustofluidic channels formed by capillary bridges two models are developed to describe nodes formed by leaky and by evanescent waves. The liquid channel held between a microscope slide (waveguide) and a strip of polystyrene film (fluid guide) avoids solid-sidewall interactions. With this simplification, our experimental and numerical study showed that waves emitted from a single plane surface, interfere and form the nodes without any resonance in the fluid. Both models pay particular attention to tensor elements normal to the solid-liquid interfaces they find that; initially nodes form in the solid and the node pattern is replicated by waves emitted into the fluid from antinodes in the stress. At fluids depths near half an acoustic wavelength, most nodes are formed by leaky waves. In the glass, water-loading reduces node-node separation and forms an overlay type waveguide which aligns the nodes predominantly along the channel. One new practical insight is that node separation can be controlled by water depth. At 0.2 mm water depths (which are smaller than a » wavelength) nodes form from evanescent waves. Here a suspension of yeast cells formed a pattern of small dot-like clumps of cells on the surface of the polystyrene film. We found the same pattern in sound intensity normal, and close, to the water-polystyrene interface. The capillary bridge channel developed for this study is simple, low-cost, and could be developed for filtration, separation, or patterning of biological species in rapid immuno-sensing applications.

Investigation of the Anti-Cancer Effects of Free and PLGA-PAA Encapsulated Hydroxytyrosol on the MCF-7 Breast Cancer Cell Line.

OBJECTIVE: Breast cancer is the most frequent cancer among women and the most important cause of death. Surgery and chemotherapy are the common treatment of breast cancer, but increasing drug resistance has created many challenges in its treatment. The present study aimed to investigate the anti-cancer function of free and nano-encapsulated hydroxytyrosol on the MCF-7 breast cancer cell line. METHODS: The poly lactide-co-glycolide-co-polyacrylic acid (PLGA-co-PAA) nanoencapsulated Hydroxytyrosol was synthesized, and the MTT assay was performed to evaluate the anti-proliferative and anti-tumor effects of both free and nano-encapsulated Hydroxytyrosol. After the extraction of RNA from the treated and control cancer cells, cDNA synthesis was performed and the expression of P21, P27, and Cyclin D1 genes was evaluated by Real-Time PCR. RESULTS: The results of the study showed that free (12 ppm and 72 hours) and nanoencapsulate (10 ppm and 24 hours) hydroxytyrosol resulted in 50% death (IC50) of the cancer cells and increased by increasing the concentration and time. Also, free and nano-encapsulated hydroxytyrosol increased the expression of P21 and P27 genes and reduced the expression of Cyclin D1 in breast cancer cells. In general, the nanoencapsulated hydroxytyrosol showed more anticancer function than the free hydroxytyrosol. CONCLUSION: The present study illustrated that hydroxytyrosol could lead to cell death in MCF-7 breast cancer by regulating the cell cycle. Also, the nano-encapsulation of Hydroxytyrosol enhanced the Hydroxytyrosol anticancer function by PLGA-co-PAA. However, for more accurate results, further studies on animal models are necessary.

Self-assembled magnetic polymeric micelles for delivery of quercetin: Toxicity evaluation on isolated rat liver mitochondria.

Multifunctional nanocarriers as a promising platform could provide numerous opportunities in the field of drug delivery. Drug carriers loaded with both magnetic nanoparticles (MNPs) and therapeutic agents would allow the combination of chemotherapy with the possibility of monitoring or controlling the distribution of the nano vehicles in the body which may improve the effectiveness of the therapy. Furthermore, by applying these strategies, triggering drug release and/or synergistic hyperthermia treatment are also reachable. This study aimed to explore the potential of the quercetin (QUR) loaded magnetic nano-micelles for improving drug bioavailability while reducing the drug adverse effects. The bio-safety of developed QUR loaded magnetic nano-micelles (QMNMs) were conducted via mitochondrial toxicity using isolated rat liver mitochondria including glutathione (GSH), malondialdehyde (MDA), and the ferric reducing ability of plasma (FRAP). QMNMs with a mean particle size of 85 nm (PDI value of 0.269) and great physical stability were produced. Also, TEM images indicated that the prepared QMNMs were semi-spherical in shape. These findings also showed that the constructed QMNMs, as a pH-sensitive drug delivery system, exhibited a stable and high rate of QUR release under mildly acidic conditions pH (5.3) compared to neutral pH (7.4). The most striking result to emerge from the data is that an investigation of various mitochondrial functional parameters revealed that both QMNMs and QUR have no specific mitochondrial toxicity. Altogether, these results offer overwhelming evidence for the bio-safety of QMNMs and might be used as an effective drug delivery system for targeting and stimuli-responsive QUR delivery.

Dexamethasone Reduces Cell Adhesion and Migration of T47D Breast Cancer Cell Line.

BACKGROUND: Aberrant expression of cell adhesion molecules and matrix metalloproteinase (MMPs) plays a pivotal role in tumor biological processes, including progression and metastasis of cancer cells. Targeting these processes and acquiring a detailed understanding of their underlying molecular mechanism are an essential step in cancer treatment. Dexamethasone (Dex) is a type of synthetic corticosteroid hormone used as adjuvant therapy in combination with current cancer treatments such as chemotherapy in order to alleviate its side effects like acute nausea and vomiting. Recent evidences suggest that Dex may have antitumor characteristics. OBJECTIVE: Dex affects the migration and adhesion of T47D breast cancer cells as well as cell adhesion molecules, e.g. cadherin and integrin, and MMPs by regulating the expression levels of associated genes. METHODS: In this study, we evaluated the cytotoxicity of Dex on the T47D breast cancer cell line through MTT assay. Cell adhesion assay and wound healing assay were performed to determine the impact of Dex on cell adhesion and cell migration, respectively. Moreover, real-time PCR was used to measure the levels of α and ß integrin, E-cadherin, N-cadherin, MMP-2, and MMP-9. RESULTS: Dex decreased the viability of T47D cells in a time and dose-dependent manner. Cell adhesion and migration of T47D cells were reduced upon Dex treatment. The expressions of α and ß integrin, E-cadherin, Ncadherin, MMP-2, and MMP-9 were altered in response to the Dex treatment. CONCLUSION: Our findings demonstrated that Dex may play a role in the prevention of metastasis in this cell line.