In-Silico and In-Vitro Investigation of Key Long Non-coding RNAs Involved in 5-Fluorouracil Resistance in Colorectal Cancer Cells: Analyses Highlighting NEAT1 and MALAT1 as Contributors.

Background Acquired resistance to 5-fluorouracil (5-FU) frequently results in chemotherapy failure and disease recurrence in advanced colorectal cancer (CRC) patients. Research has demonstrated that dysregulation of long non-coding RNAs (lncRNAs) mediates the development of chemotherapy resistance in cancerous cells. The present study aims to identify key lncRNAs associated with 5-FU resistance in CRC using bioinformatic and experimental validation approaches. Methods The Gene Expression Omnibus (GEO) dataset GSE119481, which contains miRNA expression profiles of the parental CRC HCT116 cell line (HCT116/P) and its in-vitro established 5-FU-resistant sub-cell line (HCT116/FUR), was downloaded. Firstly, differentially expressed microRNAs (DEmiRNAs) between the parental and 5-FU resistance cells were identified. LncRNAs and mRNAs were then predicted using online databases. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to uncover relevant biological mechanisms and pathways. Networks integrating lncRNAs, miRNAs, and mRNAs interactions were constructed, and topological analyses were used to identify key lncRNAs associated with 5-FU resistance. An in-vitro model of the HCT116/FUR sub-cell line was developed by exposing the HCT116/P cell line to increasing concentrations of 5-FU. Finally, real-time quantitative PCR (RT-qPCR) was performed on total RNA extracted from the HCT116/P cell line and the HCT116/FUR sub-cell line to validate the in-silico predictions of key lncRNAs. Results A total of 32 DEmiRNAs were identified. Enrichment analysis demonstrated that these DEmiRNAs were mainly enriched in several cancer hallmark pathways that regulate cell growth, cell cycle, cell survival, inflammation, immune response, and apoptosis. The predictive analysis identified 237 unique lncRNAs and 123 mRNAs interacting with these DEmiRNAs. The pathway analysis indicated that most of these predicted genes were enriched in the cellular response to starvation, protein polyubiquitination, chromatin remodeling, and negative regulation of gene expression. Topological analyses of the lncRNA-miRNA-mRNA network highlighted the nuclear enriched abundant transcript 1 (NEAT1), metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), and Opa interacting protein 5 antisense RNA 1 (OIP5-AS1) as central lncRNAs. Experimental analysis by RT-qPCR confirmed that the expression levels of NEAT1 and MALAT1 were significantly increased in HCT116/FUR cells compared to HCT116/P cells. However, no significant difference was observed in the OIP5-AS1 expression level between the two cells. Conclusion Our findings specifically highlight MALAT1 and NEAT1 as significant contributors to 5-FU resistance in CRC. These lncRNAs are promising biomarkers for diagnosing and predicting outcomes in CRC.

Comparative analysis of Escherichia coli Nissle 1917 ghosts quality: a study of two chemical methods.

The gram-negative bacterium Escherichia coli Nissle 1917 (EcN) has long been recognized for its therapeutic potential in treating various intestinal diseases. Bacterial ghosts (BGs) are empty shells of non-living bacterial cells that demonstrate enormous potential for medicinal applications. Genetic and chemical techniques can create these BGs. In the current study, we produced Escherichia coli Nissle 1917 ghosts (EcNGs) for the first time using benzoic acid (BA) and sodium hydroxide (SH). BA is a feeble acidic chemical that enhances gram-negative bacteria's external membrane permeability, reduces energy production, and decreases internal pH. SH has shown success in producing BGs from some gram-negative and gram-positive organisms. This research aims to produce EcNGs using the minimum inhibitory concentration (MIC) of SH and BA, specifically 3.125 mg/mL. We assessed the bacterial quality of the BGs produced using quantitative PCR (qPCR) and Bradford protein assays. Field emission scanning electron microscopy (FE-SEM) showed the three-dimensional structure of EcNGs. The study confirmed the presence of tunnel-like pores on the outer surface, indicating the preservation of cell membrane integrity. Importantly, this investigation introduces BA as a novel chemical inducer of EcNGs, suggesting its potential alongside SH for efficient EcNG formation.

Activation of the BMP2/SMAD4 signaling pathway for enhancing articular cartilage regeneration of mesenchymal stem cells utilizing chitosan/alginate nanoparticles on 3D extracellular matrix scaffold.

This study investigated the efficacy of using chitosan/alginate nanoparticles loaded with recombinant human bone morphogenetic-2 (rhBMP-2) and SMAD4 encoding plasmid to enhance the chondrogenesis of human bone marrow mesenchymal stem cells (hBM-MSCs) seeded on an extracellular matrix (ECM). The research treatments included the stem cells treated with the biological cocktail (BC), negative control (NC), hBM-MSCs with chondrogenic medium (MCM), hBM-MSCs with naked rhBMP-2 and chondrogenic medium (NB/C), and hBM-MSCs with naked rhBMP-2 and chondrogenic medium plus SMAD4 encoding plasmid transfected with polyethyleneimine (PEI) (NB/C/S/P). The cartilage differentiation was performed with real-time quantitative PCR analysis and alizarin blue staining. The data indicated that the biological cocktail (BC) exhibited significantly higher expression of cartilage-related genes compared to significant differences with MCM and negative control (NC) on chondrogenesis. In the (NB/C/S/P), the expression levels of SOX9 and COLX were lower than those in the BC group. The expression pattern of the ACAN gene was similar to COL2A1 changes suggesting that it holds promising potential for cartilage regeneration.

Liraglutide alleviated alpha-pyrrolidinovalerophenone (α-PVP) induced cognitive deficits in rats by modifying brain mitochondrial impairment.

The use of NPS compounds is increasing, and impairment in spatial learning and memory is a growing concern. Alpha-pyrrolidinovalerophenone (α-PVP) consumption, as a commonly used NPS, can impair spatial learning and memory via the brain mitochondrial dysfunction mechanism. Liraglutide isone of the most well-known Glucagon-Like Peptide 1 (GLP-1) agonists that is used as an anti-diabetic and anti-obesity drug. According to current research, Liraglutide likely ameliorates cognitive impairment in neurodegenerative conditions and substance use disorders. Hence, the purpose of this study is examining the effect of Liraglutide on α-PVP-induced spatial learning and memory problems due to brain mitochondrial dysfunction. Wistar rats (8 in each group) received α-PVP (20 mg/kg/d for 10 consecutive days, intraperitoneally (I.P.)). Then, Liraglutide was administered at 47 and 94 µg/kg/d, I.P., for 4 weeks following the α-PVP administration. The Morris Water Maze (MWM) task evaluated spatial learning and memory 24 h after Liraglutide treatment. Bedside, brain mitochondrial activity parameters, including reactive oxygen species (ROS) level, mitochondrial membrane potential (MMP), cytochrome c release, mitochondrial outer membrane damage and swelling, and brain ADP/ATP ratio, were studied. Our results showed that Liraglutide ameliorated α-PVP-induced spatial learning and memory impairments through alleviating brain mitochondrial dysfunction (which is indicated by increasing ROS formation, collapsed MMP, mitochondrial outer membrane damage, cytochrome c release, mitochondrial swelling, and increased brain ADP/ATP ratio). This study could be used as a starting point for future studies about the possible role of Liraglutide in ameliorating mitochondrial dysfunction leading to substance use disorder- induced cognitive impairment.

Arsenic and Benzo[a]pyrene Co-exposure Effects on MDA-MB-231 Cell Viability and Migration.

Although humans are frequently exposed to multiple pollutants simultaneously, research on their harmful effects on health has typically focused on studying each pollutant individually. Inorganic arsenic (As) and benzo[a]pyrene (BaP) are well-known pollutants with carcinogenic potential, but their co-exposure effects on breast cancer cell progression remain incompletely understood. This study aimed to assess the combined impact of BaP and As on the viability and migration of MDA-MB-231 cells. The results indicated that even at low levels, both inorganic As (0.01 µM, 0.1 µM, and 1 µM) and BaP (1 µM, 2.5 µM), individually or in combination, enhanced the viability and migration of the cells. However, the cell cycle analysis revealed no significant differences between the control group and the cells exposed to BaP and As. Specifically, exposure to BaP alone or in combination with As (As 0.01 µM + BaP 1 µM) for 24 h led to a significant increase in vimentin gene expression. Interestingly, short-term exposure to As not only did not induce EMT but also modulated the effects of BaP on vimentin gene expression. However, there were no observable changes in the expression of E-cadherin mRNA. Consequently, additional research is required to evaluate the prolonged effects of co-exposure to As and BaP on the initiation of EMT and the progression of breast cancer.

Preparation, Characterization and In vitro Evaluation of Insulin-PHBV Nanoparticles/Alginate Hydrogel Composite System for Prolonged Delivery of Insulin.

PURPOSE: In the present study, biodegradable poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) nanoparticles (NPs) containing insulin were loaded in sodium alginate/jeffamine (ALG/jeff) hydrogel for prolonged delivery of insulin. The main aim of this work was to fabricate an efficient insulin delivery system to improve patient adherence by decreasing the repetition of injections. METHODS: Swelling and morphological properties and crosslinking efficiency of ALG/jeff hydrogel were assessed. The composite hydrogel was prepared by adding PHBV NPs to ALG/jeff hydrogel concurrently with crosslinking process. The morphology and loading capacity of composite hydrogel were analyzed. RESULTS: Circular dichroism measurement demonstrated that insulin remains stable following fabrication process. The release profile exhibited 54.6 % insulin release from composite hydrogel within 31 days with minor initial burst release equated to nanoparticles and hydrogels. MTT cell viability analysis was performed by applying L-929 cell line and no cytotoxic effect was observed. CONCLUSIONS: Favorable results clearly introduced fabricated composite hydrogel as an excellent candidate for drug delivery systems and also paves the route for prolonged delivery systems of other proteins.

Bisphenol A in dairy products, amount, potential risks, and the various analytical methods, a systematic review.

This systematic study deals with the amount of bisphenol A (BPA) in milk and dairy products, its analytical methods, and risk assessment. Milk is one of the drinks that has a high consumption. Bisphenol A can be present both in raw milk and its amount undergoes changes during the pasteurization process. This review was conducted by searching for the keywords Bisphenol A, BPA milk, dairy product, cheese, cream, butter, yogurt, measurement, detection, and analysis in different databases. The search was done in three databases, Scopus, PubMed and Science Direct. The largest number of studies on the determination of bisphenol A belonged to Asian and European countries. The amount of bisphenol A in milks was observed in the range from ND to 640 ng/mL. Furthermore, the amount of BPA in the tested cheese samples was observed in the ND range up to 6.1 ng/g and in the yogurt samples in the ND range up to 4.4 ng/g. The most used analytical method was based on liquid chromatography. The most used solvent for extraction was methanol or acetonitrile. HQ (Hazard Quotient) was also calculated in some studies. There was no risk in terms of milk consumption due to BPA contamination in extracted data.

Aptamer-modified chitosan-capped mesoporous silica nanoparticles for co-delivery of cytarabine and daunorubicin in leukemia.

In this study, surface modified mesoporous silica nanoparticles (MSNs) were prepared for the targeted delivery of the anticancer agents, daunorubicin (DNR) and cytarabine (CTR), against K562 leukemia cancer cell lines. The MSNs were surface-modified with pH-sensitive chitosan (CS) to prevent the burst release of anticancer agents at the physiological pH of 7.4 and to enable a higher drug release at lower pH and higher concentration of glutathione. Finally, the MSNs were surface modified with KK1B10 aptamer (Apt) to enhance their uptake by K562 cells through ligand-receptor interactions. The MSNs were characterized using different methods and both in vitro and in vivo experiments were utilized to demonstrate their suitability as targeted anticancer agents. The resultant MSNs exhibited an average particle size of 295 nm, a surface area of 39.06 m2/g, and a cumulative pore volume of 0.09 cm3/g. Surface modification of MSNs with chitosan (CS) resulted in a more regulated and acceptable continuous release rate of DNR. The drug release rate was significantly higher at pH 5 media enriched with glutathione, compared to pH 7.4. Furthermore, MSNs coated with CS and conjugated with aptamer (MSN-DNR + CTR@CS-Apt) exhibited a lower IC50 value of 2.34 µg/ml, compared to MSNs without aptamer conjugation, which displayed an IC50 value of 12.27 µg/ml. The results of the cell cycle analysis indicated that the administration of MSN-DNR + CTR@CS-Apt led to a significant increase in the population of apoptotic cells in the sub-G1 phase. Additionally, the treatment arrested the remaining cells in various other phases of the cell cycle. Furthermore, the interactions between Apt-receptors were found to enhance the uptake of MSNs by cancer cells. The results of in vivo studies demonstrated that the administration of MSN-DNR + CTR@CS-Apt led to a significant reduction in the expression levels of CD71 and CD235a markers, as compared to MSN-DNR + CTR@CS (p < 0.001). In conclusion, the surface modified MSNs prepared in this study showed lower IC50 against cancer cell lines and higher anticancer activity in animal models.

Waterborne polyurethane magnetic nanomicelles with magnetically governed functions for breast cancer therapy.

Drug delivery strategies aim to maximize a drug's therapeutic efficiency by increasing the drug's concentration at the target site while minimizing delivery to off-target tissues. There is a great deal of interest in using magnetic nanoparticles in combination with applied magnetic fields to selectively control drug accumulation and release in target tissue while minimizing effects on other tissues. In this study, a magnetic targeted drug delivery system based on waterborne polyurethane nanomicelles was prepared by encapsulating hydrophobic doxorubicin (DOX, model drug) and hydrophobic oleic acid-superparamagnetic nanoparticles (SPION-OA) into the hydrophobic core of waterborne polyurethane micelles (CPUM) using the solvent evaporation method. The prepared drug-loaded magnetomicelles (CPUM-DOX-SPION) had a spherical shape with an average diameter of 158 nm. The magnetomicelles showed superparamagnetic properties with excellent magnetic resonance imaging (MRI) contrast effects and T2 relaxation in vitro. In the absence and presence of a magnetic field, the cytocompatibility and cellular uptake of the samples were assessed by MTT assay and flow cytometry, respectively, and the cells were imaged with a confocal microscope. Application of the magnetic field increased cellular cytotoxicity and cellular uptake in association with improved DOX delivery. In addition, the in vivo study of tumor volume showed that tumor growth of the mice group treated with CPUM-DOX-SPION in the presence of an external magnetic field was significantly retarded, with no apparent loss of body weight, compared with the same magnetomicelles in the absence of the magnetic field and with free DOX at the same dose. Moreover, the in vivo MRI experiment indicated the potential of these magnetomicelles as a probe in MRI diagnosis for tumor targeting, and the results showed that magnetically guided delivery of CPUM-SPION magnetomicelles into tumors could significantly improve the targeting efficacy. All the results suggest that the prepared novel magnetomicelles will be promising theranostic systems for effective magnetically guided delivery of chemotherapeutic agents and image-guided personalized medicine.

Bacillus subtilis supernatant improves the efficacy of radiation therapy in rat intestinal epithelial cells by upregulation of bax and caspase-3 genes.

BACKGROUND: Colorectal Cancer (CC) is among the most prevalent cancers in elderly persons. Radiotherapy is usually prescribed as CC develops, however, radiation beams indiscriminately affect normal cells. Previous studies nominated that probiotics and their metabolites can be used to minimize the side effects of radiotherapy. Hereby, the aim of this study was to investigate the probable correlation between cell-free supernatant of Bacillus subtilis and radiation response in normal and cancerous cell lines. METHODS AND RESULTS: IEC-18 and SW-48 cells were treated with different concentrations of B. subtilis supernatant. To evaluate the effect of probiotic treatments under radiation and the normal situation, the cytotoxicity of the treatments was measured using the MTT method. The cell cycle status was analyzed by flow cytometry. The expression levels of Bax, Bcl-2, and Caspase 3 genes were also determined by real-time (RT) PCR. B. subtilis supernatant increased the viability of normal cells under radiation treatment, although this effect was not significant. 40% v/v of this mixture could amplify the lethal effect of radiation and decreased the viability of cancer cells. SW-48 cells that received 40% v/v of the supernatant had a significantly higher rate of apoptosis. Probiotic supernatant effectively induced the expression of proapoptotic Bax and Caspase 3 genes. CONCLUSION: Presented results confirmed that the supernatant of B. subtilis can be supposed as a clue to improve the efficacy of radiation therapy in CC patients as it increased the sensitivity of cancerous cells and protected normal epithelial cells from detrimental effects of radiation.

Radio-immunotherapy by 188Re-antiCD20 and stable silencing of IGF-IR in Raji cells, new insight in treatment of lymphoma.

Hematologic malignancies such as Non-Hodgkin's lymphoma (NHL), remain a serious threat to human health due to their heterogeneity and complexity. The inherent genetic heterogeneity of NHL B-cells, as well as the instability of lymphoma cancer cells, results in drug resistance in lymphoma, posing a fundamental challenge to NHL treatment. Burkitt lymphoma (including Raji cell line) is a rare and highly aggressive form of B-cell NHL. Since overexpression of the insulin-like growth factor-1 receptor (IGF-1R) playing a prominent role in the development and transformation of different malignancies, especially lymphoma malignancies, we have explored the role of IGF-1R in the development and progression of Raji cells and the stable silencing of IGF-1R by lentivirus-mediated RNA interference (RNAi). We have shown that stable silencing of the IGF-1R gene in Raji cells using lentivirus-mediated-RNAi have resulted in a significant reduction in Raji cell proliferation. Moreover, the results of the cell viability assays indicatedhigh resistance of Raji cells to rituximab. However, coupling rituximab to 188Re potentially leads to specific targeting of Raji cells by 188Re, improving the therapeutic efficacy. We found that the synergistic effect of using a gene therapy-based system in combination with radioimmunotherapy could be a promising therapeutic strategy in the future. To the best of our knowledge, this is the first study that reports the knock down of IGF-1R via lentiviral-mediated shRNA in Raji cells.

Effect of citalopram and sertraline on the expression of miRNA- 124, 132, and 16 and their protein targets in patients with depression.

Objectives: This study aimed to evaluate the effect of SSRIs on the expression of miRNAs and their protein targets. Materials and Methods: In a 100 day open-label study of citalopram (n=25) and sertraline (n=25), levels of miRNA 16, 132, and 124 and glucocorticoid receptor (GR), Brain-derived neurotrophic factor (BDNF), and serotonin transporter (SERT) protein expression were measured by QRT-PCR and western blot in healthy control (n=20), patients with depression at the baseline, and same patients after 100 days of treatment. Results: Expression levels of GR and BDNF proteins were lower in the depressed group before treatment as compared with the healthy group (P<0.0001). The SERT level was higher among the depressed group before treatment in comparison with the healthy group (P<0.0001). The level of GR and BDNF significantly increased, and SERT expression decreased after receiving sertraline (P<0.05). When the depressed group received citalopram, only SERT and GR were altered (P<0.05). Among the microRNAs' expression investigated, mir-124 and mir-132 were higher, and mir-16 was lower among the depressed compared with the healthy group (P<0.0001). Individuals receiving citalopram only showed an increase in the expression of mir-16 while administration of sertraline led to a significant increase in the expression of mir-16 and a decrease in mir-124 and mir-132 (P<0.05). Conclusion: This elucidated the relationship between antidepressant treatment and the expression of different microRNA that control gene expression in various pathways involved in depressed patients. Receiving SSRI can affect the level of these proteins and their relevant microRNAs.

Chromosome conformation capture-based DNA hybridization method for chromosomal translocation screening.

Background: DNA probes have been widely used as diagnostic tools for translocations. This study sought to design a screening tool using ssDNA probes and chromosome conformation capture (3C) library fragment hybridization. Method: The authors focused on developing a probe for the juxtaposed region of MYC and TRD. Fragments of the MYC gene with a thiol modification (MYC-Au NP probe) were functionalized by gold nanoparticles (Au NPs). Then TRD probes were immobilized on a nitrocellulose surface. Hybridization between DNA probes and 3C library fragments of SKW3 cells was determined by color intensity. Results: Optimal hybridization of the 3C library sample of the cell line to probes showed higher color intensity than human umbilical vein endothelial cells. Conclusion: Combining 3C-based techniques and DNA-DNA hybridization can identify rearrangements in cancer cells.

Alpha pyrrolidinovalerophenone (α-PVP) administration impairs spatial learning and memory in rats through brain mitochondrial dysfunction.

Novel psychoactive substances (NPS) consumption has increased in recent years, thus NPS-induced cognitive decline is a current source of concern. Alpha-pyrrolidinovalerophenone (α-PVP), as a member of NPS, is consumed throughout regions like Washington, D.C., Eastern Europe, and Central Asia. Mitochondrial dysfunction plays an essential role in NPS-induced cognitive impairment. Meanwhile, no investigations have been conducted regarding the α-PVP impact on spatial learning/memory and associated mechanisms. Consequently, our study investigated the α-PVP effect on spatial learning/memory and brain mitochondrial function. Wistar rats received different α-PVP doses (5, 10, and 20 mg/kg) intraperitoneally for 10 sequential days; 24 h after the last dose, spatial learning/memory was evaluated by the Morris Water Maze (MWM). Furthermore, brain mitochondrial protein yield and mitochondrial function variables (Mitochondrial swelling, succinate dehydrogenase (SDH) activity, lipid peroxidation, Mitochondrial Membrane Potential (MMP), Reactive oxygen species (ROS) level, brain ADP/ATP proportion, cytochrome c release, Mitochondrial Outer Membrane (MOM) damage) were examined. α-PVP higher dose (20 mg/kg) significantly impaired spatial learning/memory, mitochondrial protein yield, and brain mitochondrial function (caused reduced SDH activity, increased mitochondrial swelling, elevated ROS generation, increased lipid peroxidation, collapsed MMP, increased cytochrome c release, elevated brain ADP/ATP proportion, and MOM damage). Moreover, the lower dose of α-PVP (5 mg/kg) did not alter spatial learning/memory and brain mitochondrial function. These findings provide the first evidence regarding impaired spatial learning/memory following repeated administration of α-PVP and the possible role of brain mitochondrial dysfunction in these cognitive impairments.

Electrochemiluminescent immunosensor for detection of carcinoembryonic antigen using luminol-coated silver nanoparticles.

Recently, electrochemiluminescent (ECL) immunosensors have received much attention in the field of biomarker detection. Here, a highly enhanced ECL immunosensing platform was designed for ultrasensitive detection of carcinoembryonic antigen (CEA). The surface of the glassy carbon electrode was enhanced by applying functional nanostructures such as thiolated graphene oxide (S-GO) and streptavidin-coated gold nanoparticles (SA-AuNPs). The selectivity and sensitivity of the designed immunosensor were improved by entrapping CEA biomolecules using a sandwich approach. Luminol/silver nanoparticles (Lu-SNPs) were applied as the main core of the signaling probe, which were then coated with streptavidin to provide overloading of the secondary antibody. The highly ECL signal enhancement was obtained due to the presence of horseradish peroxidase (HRP) in the signaling probe, in which the presence of H2O2 further amplified the intensity of the signals. The engineered immunosensor presented excellent sensitivity for CEA detection, with limit of detection (LOD) and linear detection range (LDR) values of 58 fg mL-1 and 0.1 pg mL-1 to 5 pg mL-1 (R2 = 0.9944), respectively. Besides its sensitivity, the fabricated ECL immunosensor presented outstanding selectivity for the detection of CEA in the presence of various similar agents. Additionally, the developed immunosensor showed an appropriate repeatability (RSD 3.8%) and proper stability (2 weeks). Having indicated a robust performance in the real human serum with stated LOD and LDR, the engineered immunosensor can be considered for the detection and monitoring of CEA in the clinic.

Elucidation of flavonoids from potent Iranian Scutellaria species against Influenza A (H1N1) virus.

Objectives: Influenza A virus (IAV) is a contagious illness. Different species of Scutellaria genus are used as a traditional remedy to reduce influenza symptoms. This study aimed to investigate the anti-influenza capacity of several species of Iranian Scutellaria and identify active compounds of the most potent species for the first time. Materials and Methods: Some Iranian species of Scutellaria were collected from different regions of Iran, including S. pinnatifida with mucida, viridis, and alpina subspecies; S. tournefortii; S. tomentosa; S. persica. They were fractionated to chloroform and methanol. The total phenols and flavonoids of samples were examined by the folin-ciocalteau and aluminum-flavonoid complex methods, respectively. The 50% cytotoxic concentrations (CC50) on MDCK cells and non-cytotoxic concentrations (NCTC) were determined by MTT assay. The percentage of cell protection against IAV and their effect on virus titer were investigated in pre-, post-, and co-penetration treatment groups. Phytochemicals of the most effective species were isolated by various chromatographic methods and identified by different spectroscopic methods. Results: Methanol fraction of S. pinnatifida subsp. viridis demonstrated the highest amounts of flavonoid content and best activity against influenza A virus in all combination treatments, which reduced the virus titer by 5 logs with no cytotoxicity. Kaempferol-3-O-glucoside, quercetin-3-O-glucoside, apigenin-4'-methoxy-7-O-glucoside, luteolin, and luteolin-7-O-glucoside were purified and identified from this species. Conclusion: Scutellaria pinnatifida subsp. viridis can be introduced as a source of flavonoids with acceptable anti-influenza activity. S. tomentosa also showed potent antiviral effects and is a candidate for elucidation in further studies.

Quercetin Effects on Cell Cycle Arrest and Apoptosis and Doxorubicin Activity in T47D Cancer Stem Cells.

BACKGROUNDS: Targeting breast cancer stem cells with the CD44+/CD24- phenotype is critical for complete eradication of cancer cells due to its Self-renewal, differentiation, and therapeutic resistance ability. Quercetin is a popular flavonoid with lower adverse effects and has anti-tumor properties. Therefore, we assessed the anticancer activity of Quercetin and Doxorubicin alone and in combination in the T47D cells of human breast cancer and their isolated Cancer stem cells (CSCs). MATERIALS AND METHODS: The human breast cancer cell line T47D was used for this experiment. T47D CSCs were isolated by magnetic bead sorting using the MACS system. The anticancer activity of Quercetin and Doxorubicin alone and in combination were evaluated using MTT cytotoxicity assay and cell cycle distribution and apoptosis induction by flow cytometry analysis. RESULTS: We have shown that almost 1% of T47D cell populations are made up of CD44+/CD24- cells, which considered as cancer stem cells. Quercetin and Doxorubicin alone or in combination inhibited cell proliferation and induced apoptosis in breast cancer T47D cells and in lower extent in CD44+/CD24- cells. Quercetin significantly strengthened Doxorubicin's cytotoxicity and apoptosis induction in both cell populations. Quercetin and Doxorubicin and their combination induced G2/M arrest in the T47D cells and to a lesser extent in isolated CSCs. A value of p < 0.05 was considered as indicating a statistically significant difference. CONCLUSION: These outcomes suggested that CSCs are a minor population of cancer cells, which play a significant role in drug resistance by being quiescent, slow cycling and resistance to apoptosis. Furthermore, our data showed that adding Quercetin to Doxorubicin is an effective approach for the treatment of both CSCs and bulk tumor cells.

Evaluation of DNA methylation in BDNF, SLC6A4, NR3C1 and FKBP5 before and after treatment with selective serotonin-reuptake inhibitor in major depressive disorder.

Aim: To identify the DNA methylation status of related genes in major depressive disorder following selective serotonin-reuptake inhibitor treatment. Materials & methods: 45 patients with major depressive disorder and 45 healthy volunteers were considered experimental and control groups, respectively. High-resolution melting real-time PCR was implemented to evaluate DNA methylation. Results: After 100 days of selective serotonin-reuptake inhibitor treatment, methylation of promoter CpG sites of BDNF, NR3C1, FKBP5 and SLC6A4 was significantly reduced. Compared with before treatment, patients' Hamilton Depression Rating Scale scores were significantly reduced after selective serotonin-reuptake inhibitor treatment (p ≤ 0.0001). Conclusion: Based on the proven effect of antidepressants on DNA methylation and gene expression, these medications can improve the treatment process and reduce depression scores after treatment.

Cancer cells as a new source of induced pluripotent stem cells.

Over the last 2 decades, induced pluripotent stem cells (iPSCs) have had various potential applications in various medical research areas, from personalized medicine to disease treatment. Different cellular resources are accessible for iPSC generation, such as keratinocytes, skin fibroblasts, and blood or urine cells. However, all these sources are somatic cells, and we must make several changes in a somatic cell's transcriptome and chromatin state to become a pluripotent cell. It has recently been revealed that cancer cells can be a new source of iPSCs production. Cancer cells show similarities with iPSCs in self-renewal capacity, reprogramming potency, and signaling pathways. Although genetic abnormalities and potential tumor formation in cancer cells pose a severe risk, reprogrammed cancer-induced pluripotent stem cells (cancer-iPSCs) indicate that pluripotency can transiently overcome the cancer phenotype. This review discusses whether cancer cells can be a preferable source to generate iPSCs.