Investigating the Effect of Satureja khuzestanica Essential oil on MDR1 Gene Expression in Leishmania major.

BACKGROUND: Cutaneous leishmaniasis is among the neglected diseases in the world. Pentavalent antimonial compounds are considered the first-line treatment for this disease. However, using alternative natural products has received great attention due to the side effects of chemical drugs and drug resistance of the Leishmania parasite. The present study aims to investigate the effect of Satureja khuzestanica essential oil (SKEO) on MDR1 gene expression. METHODS: In this study, standard strains of Leishmania major promastigotes were exposed to 5, 10, 15, and 20 µg/ml of SKEO. MDR1 gene expression of parasites exposed to essential oil was evaluated using real-time PCR. GAPDH was employed as the housekeeping gene for internal control. RESULTS: Despite the increase, no statistically significant difference was observed in the relative expression of the MDR1 gene between the control group and the groups containing 5, 10, and 20 µg/ml of SKEO (P > 0.05). The relative expression of the MDR1 gene significantly increased in the group containing 15 µg/ml of essential oil compared to the control one (P < 0.05). CONCLUSION: This study showed that the use of essential oil of Satureja khuzestanica plant can have an increasing effect on the expression of MDR1 gene of Leishmania promastigotes, which is the best case if Satureja khuzestanica essential oil reduces the expression of MDR1 gene. So it seems that the use of essential oil of Satoria plant is effective in controlling Leishmania parasite, but its concentrations induce drug resistance. As a result, concentrations of essential oil should be used that have a controlling effect on the growth and proliferation of Leishmania parasite and also have the least effect on the induction of MDR1 gene expression.

Ovarian Torsion and Oophorectomy in Childhood: A Case Report.

BACKGROUND: Ovarian torsion in infants can be asymptomatic or may present with abdominal mass and malnutrition. It is an uncommon and non-specific condition in children. We report a girl who underwent detorsion and ovariopexy for suspected ovarian torsion after a previous oophorectomy. The role of progesterone therapy is determined in reducing the size of adnexal mass. CASE PRESENTATION: The patient was diagnosed with right ovarian torsion and underwent an oophorectomy at one year of age. About 18 months later, she was diagnosed with left ovarian torsion and underwent detorsion with lateral pelvic fixation. Despite the pelvic fixation of the ovary, a continuous increase in the volume of the ovarian tissue was evident during successive ultrasounds. Progesterone therapy was started at five years of age in order to prevent retorsion and preserve the ovarian tissue. In successive follow-ups during the therapy, ovarian volume decreased, and its size (27*18 mm) was restored. CONCLUSION: The presented case reminds doctors of the possibility of ovarian torsion in young girls with pelvic pain. More research is needed on the use of hormonal drugs, such as progesterone, in similar cases.

Colorectal cancer-secreted exosomal circ_001422 plays a role in regulating KDR expression and activating mTOR signaling in endothelial cells by targeting miR-195-5p.

BACKGROUND: As non-coding RNAs, exosomal circular RNAs (circRNAs) regulate colorectal cancer (CRC) progression, although the functional mechanisms by which such molecules affect the tumor microenvironment are still elusive. Herein, we aimed to explore the potential clinical significance of a signature of five serum-derived circRNAs in CRC and investigated the mechanisms underlying endothelial cell angiogenesis mediated by CRC-secreted exosomal circ_001422. METHODS: The expression of a signature of five serum-derived circRNAs (circ_0004771, circ_0101802, circ_0082333, circ_0072309, and circ_001422) were measured by RT-qPCR, and their associations with tumor staging and lymph node metastasis were further evaluated in CRC patients. In silico analysis was used to show the relationship between circ_001422, miR-195-5p, and KDR, validated by dual-luciferase reporter and Western blotting assays. CRC cell-derived exosomes were isolated and characterized by scanning electron microscopy and Western blotting. Endothelial cell uptake of PKH26-labeled exosomes was demonstrated using a spectral confocal microscope. In vitro genetic strategies were used to exogenously alter the expression level of circ_001422 and miR-195-5p expression. Cell proliferation assay, transwell migration assay, and capillary tube formation assay were conducted to explore the role of CRC-secreted exosomal circ_001422 in endothelial cell function in vitro. RESULTS: The expression levels of serum-derived circ_0004771, circ_0101802, circ_0082333, and circ_001422 were significantly higher in CRC and were positively correlated with the lymph node metastasis status. However, circ_0072309 showed a significant down-regulation in CRC than in healthy individuals. Furthermore, a higher expression level of circ_001422 in both cellular and exosomal fractions was found in HCT-116 CRC cells. We found that HCT-116 exosomes considerably enhanced proliferation and migration of endothelial cells through shuttling of circ_001422. We also observed that exosomes derived from HCT-116 cell, but not non-aggressive Caco-2 CRC cells, increased in vitro tubulogenesis of endothelial cells. Importantly, knockdown of circ_001422 impaired the capability of endothelial cells to form the capillary-like tube structures. CRC-secreted circ_001422 acted as an endogenous miR-195-5p sponge to inhibit miR-195-5p activity, which led to increased KDR expression and mTOR signaling activation in endothelial cells. Importantly, ectopic expression of miR-195-5p mimicked the effect of circ_001422 silencing on KDR/mTOR signaling in endothelial cells. CONCLUSION: This study attributed a biomarker role for circ_001422 in CRC diagnosis and proposed a novel mechanism whereby circ_001422 up-regulates KDR through sponging miR-195-5p. These interactions may give rise to the activation of mTOR signaling and may be a possible clarification for the pro-angiogenesis effects of CRC-secreted exosomal circ_001422 on endothelial cells.

The effect of cognitive-behavioral counseling with or without Citrus aurantium essential oil on sleep quality in pregnant women: a randomized controlled trial.

Sleep disorder is very common during pregnancy. Non-pharmacological treatments are a priority to improve the sleep pattern. This study aimed to determine the effect of cognitive-behavioral counseling with or without Citrus aurantium essential oil on sleep quality (primary outcome) and anxiety and quality of life (secondary outcomes). This randomized controlled trial was performed on 75 pregnant women in Tabriz, Iran. Participants were randomly assigned to the intervention and control groups. The first intervention group received 8 sessions of cognitive-behavioral counseling and aromatherapy with Citrus aurantium essential oil 15-20 min before bedtime. The second intervention group received cognitive-behavioral counseling and aromatherapy with placebo and the control group received only routine prenatal care. Pittsburgh Sleep Quality Index, Pregnancy-Specific Quality of life Questionnaire, and Pregnancy-Specific Anxiety Scale were completed before and after intervention. After the intervention based on ANCOVA test and by adjusting the baseline score, the mean score of anxiety in the intervention group 1 (AMD: - 4.54; 95% CI - 6.79 to - 2.28) and intervention group 2 (AMD: - 3.30; 95% CI - 5.60 to - 0.97) was significantly lower than the control group. Also, the mean score of quality of life in intervention group 1 (AMD: 2.55; 95% CI 0.45-4.65) and intervention group 2 (AMD: 2.72; 95% CI 0.60-4.83) was significantly higher than the control group, but there was no statistically significant difference between the study groups in terms of sleep quality (P > 0.05). Also, there was no statistically significant difference between the two intervention groups after the intervention in terms of anxiety (P = 0.379) and quality of life (P = 0.996). Cognitive-behavioral counseling reduced anxiety and improved quality of life. However, further trials are required to reach a definitive conclusion. Iranian Registry of Clinical Trials (IRCT): IRCT20120718010324N63. Date of registration: 4/10/2020. URL: https://en.irct.ir/user/trial/54986/view; Date of first registration: 18/10/2020.

Retinoic acid-inducible gene 1 (RIG-1) and IFN-ß promoter stimulator-1 (IPS-1) significantly down-regulated in the severe coronavirus disease 2019 (COVID-19).

INTRODUCTION: Retinoic acid-inducible gene 1 (RIG-1) and melanoma differentiation-associated protein 5 (MDA5) are the well-known cytoplasmic sensors that recognize microbial DNA or RNA and active down-stream molecules, including IFN-ß promoter stimulator-1 (IPS-1) and receptor interacting protein 1 (RIP1). The roles played by the networked molecules on the infection with SARS-CoV-2 needs more investigations. MATERIAL AND METHOD: In this project MDA5, RIG-1, IPS-1 and RIP1 mRNA levels were evaluated in 45 hospitalized patients suffering from coronavirus disease of 2019 (COVID-19) and 45 healthy subjects using Real Time-qPCR technique. RESULT: The results showed significant decreased RIG-1 and IPS-1 in the SARS-CoV-2 infected patients when compared to healthy cases. MDA5 and RIP1 did not change when compared two groups. Male patients had similar expression of MDA5, RIG-1, IPS-1 and RIP1 when compared to female patients. CONCLUSION: Based on the results, it seems that RIG-1 and its signaling molecule, IPS-1, play key roles in the peripheral blood immune cells against SARS-CoV-2 and, their down-regulation may be induced by the virus to escape from immune responses.

Identification of a six-microRNA signature as a potential diagnostic biomarker in breast cancer tissues.

BACKGROUND: Breast cancer (BC) is by far the most common malignancy among women. Epigenetic modulators, microRNAs in particular, may set stages for BC development and its progression. Herein, we aimed to assess the diagnostic potentiality of a signature of six miRNAs (i.e., hsa-miR-25-3p, -29a-5p, -105-3p, -181b1-5p, -335-5p, and -339-5p) in BC and adjacent non-tumor tissues. METHODS: A pair of 50 tumor and adjacent non-tumor samples were taken from BC patients. The expression of each candidate miRNA was measured using quantitative reverse transcription PCR. To investigate the possible roles of each miRNA and their impressions on BC prognosis, in silico tools were used. Receiver operating characteristic (ROC) curves were performed to determine the diagnostic accuracy of each miRNA and the possible association of their expression with clinicopathological characteristics was analyzed. RESULTS: Our findings showed the upregulation of hsa-miR-25-3p, -29a-5p, -105-3p, and -181b1-5p, and the downregulation of hsa-miR-335-5p and -339-5p in BC tumor compared to corresponding adjacent tissues. Except for hsa-miR-339-5p, the up-/down-regulation of the candidate miRNAs was associated with TNM stages. Except for hsa-miR-105-3p, each candidate miRNA was correlated with HER-2 status. ROC curve analysis showed that the signature of six-miRNA is a potential biomarker distinguishing between tumor and non-tumor breast tissue samples. CONCLUSION: We showed that the dysregulation of a novel signature of six-miRNA can be used as a potential biomarker for BC diagnosis.

Induction of anxiolytic, antidepressant and analgesic effects by Shiff base of (E)-3-(1H-imidazol-4-yl)-2-((2-oxoindolin-3-ylidene)amino)propanoic acid derivatives in diabetic rats.

Diabetes mellitus is a metabolic disorder with several psychological problems such as anxiety, depression, and pain sense. This study aimed to evaluate the effect of Schiff base on the modulation of anxiety, depression, and pain behaviors in diabetic rats. Anxiety, depression, and pain behaviors were evaluated by elevated plus maze (EPM), forced swim test (FST), and hot-plate test, respectively. The results indicated that induction of diabetes decreased time spent in open arms (OAT) in the EPM whereas injection of insulin (1 ml/kg), glibenclamide (5 mg/kg), and Schiff base II (100 mg/kg) increased OAT in the EPM. So, induction of diabetes in rats caused an anxiogenic effect that this effect reversed by drug treatment. Interestingly, co-treatment of insulin and glibenclamide along with an ineffective dose of Schiff base II potentiated anxiolytic behavior in diabetic rats. Furthermore, induction of diabetes increased immobility time in the FST but administration of insulin (1 ml/kg), glibenclamide (5 mg/kg), and Schiff base II (25, 50, and 100 mg/kg) decreased immobility time in the FST which indicated depressant effect in diabetic rats without drug-treatment and antidepressant effect in diabetic rats with drug-treatment. Additionally, induction of diabetes decreased latency in the hot-plate test while injection of insulin (1 ml/kg), glibenclamide (5 mg/kg), Schiff base I (50 mg/kg), and Schiff base II (25, 50, and 100 mg/kg) enhanced latency in the hot-plate test which revealed hyperalgesic effect in diabetic rats without drug-treatment and analgesic effect in diabetic rats with drug-treatment. Consequently, induction of diabetes-induced anxiogenic, depressant, and hyperalgesia effects that administration of insulin, glibenclamide, Schiff bases I, and II reversed these effects.

Let-7d and miR-185 Impede Epithelial-Mesenchymal Transition by Downregulating Rab25 in Breast Cancer.

OBJECTIVE: MicroRNAs (miRNAs) expression has deregulated in several cancer types including breast cancer (BC). The present study aims at investigating the role, mechanism, clinical value of let-7d and miR-185 in BC, and the possible correlation these miRNAs with Rab25. MATERIALS AND METHODS: Tumor samples as well adjacent normal tissues (ANT) were acquired from fresh surgical specimens from 110 patients and the expression levels of let-7d, miR-185, Rab25, and snail were evaluated using real-time PCR. The immunohistochemical (IHC) process and western blot were done to detect the level of Rab25 and Snail protein expression in BC samples. RESULTS: By comparing miRNAs expression profiles in clinical tissues of 110 patients using real-time PCR, let-7d, and miR-185 expression were dramatically downregulated in BC tissues (P < 0.05). Tumor size, stage, and lymph node metastasis were significantly related to miRNAs expression. Based on qRT-PCR and bioinformatics database analyses, we also recognized Rab25 as a possible target of miR-185 and let-7d. Rab25 expression was enhanced in BC cells and associated inversely with the expression level of mentioned miRNAs. qRT-PCR, immunohistochemistry, and western blot studies verified that Rab25 upregulation increased the levels of the snail, that key transcription factor of epithelial-mesenchymal transition (EMT). CONCLUSION: These findings demonstrated that let-7d and miR-185 inhibited EMT by targeting Rab25 expression in BC. Therefore, targeting the let-7d and miR-185/Rab25 interaction may offer new therapeutic opportunities for treating BC patients.
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Upregulation of the long noncoding RNAs DSCAM-AS1 and MANCR is a potential diagnostic marker for breast carcinoma.

Breast cancer (BC) is one of the most common malignancies among women in the world. There is a global attempt to diagnose BC as early as possible. Long noncoding RNAs (lncRNAs) are emerging as novel targets and biomarkers for BC diagnosis and prognosis. Aberrant expression of lncRNAs is associated with BC development, making them a potential tumor marker for BC. To investigate this possibility, we determined the expression levels of Down syndrome cell adhesion molecule-antisense RNA-1 (DSCAM-AS1) and mitotically-associated long non-coding RNA (MANCR) lncRNAs in BC tissues. This case-control study included 50 paired tumor and adjacent nontumor tissues from female BC patients. The total RNA was isolated and the expression levels of MANCR and DSCAM-AS1 lncRNAs were assessed using quantitative real-time reverse transcription-PCR. Potential correlations between lncRNA levels and clinicopathological characteristics were also analyzed. DSCAM-AS1 and MANCR lncRNAs were significantly upregulated in BC tumor tissues compared with the adjacent nontumor tissues. We also found the significant upregulation of DSCAM-AS1 in advanced tumor-node-metastasis stage (TNM III) of BC tumor tissues. Furthermore, the expression of DSCAM-AS1 and MANCR in HER-2 positive patients was significantly higher than HER-2 negative affected individuals. Receiver operating characteristic curve analysis showed a satisfactory diagnostic efficacy (P value < 0.0001), which means that DSCAM-AS1 and MANCR lncRNAs can potentially serve as a biomarker. The present study might provide further approval for the clinical diagnostic significance of DSCAM-AS1 and MANCR lncRNAs that their high expressions were associated with aggressive clinical parameters of BC.

Advances of exosome isolation techniques in lung cancer.

Lung cancer (LC) is among the leading causes of death all over the world and it is often diagnosed at advanced or metastatic stages. Exosomes, derived from circulating vesicles that are released from the multivesicular body, can be utilized for diagnosis and also the prognosis of LC at early stages. Exosomal proteins, RNAs, and DNAs can help to better discern the prognostic and diagnostic features of LC. To our knowledge, there are various reviews on LC and the contribution of exosomes, but none of them are about the exome techniques and also their efficiency in LC. To fill this gap, in this review, we summarize the recent investigations regarding isolation and also the characterization of exosomes of LC cells. Furthermore, we discuss the noncoding RNAs as biomarkers and their applications in the diagnosis and prognosis of LC. Finally, we compare the efficacy of exosome isolation methods to better fi + 6 + guring out feasible techniques.

Recent advances in electrospun nanofiber-mediated drug delivery strategies for localized cancer chemotherapy.

Nanotechnology empowered localized cancer chemotherapy has indicated a promising performance for targeting and controlled release of anticancer agents over a period of time to eliminate local-regional recurrence of cancers and also to improve the tissue regeneration during/after treatment. Electrospun nanofiber-based implantable drug-delivery systems have been established as one of the most effective approaches for localized cancer treatment, allowing the on-site delivery of anticancer agents and reducing systemic toxicities and side effects to normal cells. The present review aimed to summarize the latest cutting-edge research on applications of electrospun-based systems for local chemotherapy. Meantime, in vitro and in vivo studies conducted using various anticancer agents along with the capability of electrospun nanofibers for combinatorial/synergistic chemotherapy as well as existing challenges and the potential dramatic advances in applying this pioneering approach for clinical transition in localized treatments of cancer is also discussed.

Recent advances on nanomaterials-based fluorimetric approaches for microRNAs detection.

MicroRNAs are types of small single-stranded endogenous highly conserved non-coding RNAs, which play main regulatory functions in a wide range of cellular and physiological events, such as proliferation, differentiation, neoplastic transformation, and cell regeneration. Recent findings have proved a close association between microRNAs expression and the development of many diseases, indicating the importance of microRNAs as clinical biomarkers and targets for drug discovery. However, due to a number of prominent characteristics like small size, high sequence similarity and low abundance, sensitive and selective identification of microRNAs has rather been a hardship through routine traditional assays, including quantitative polymerase chain reaction, microarrays, and northern blotting analysis. More recently, the soaring progression in nanotechnology and fluorimetric methodologies in combination with nanomaterials have promised microRNAs detection with high sensitivity, efficiency and selectivity, excellent reproducibility and lower cost. Therefore, this review will represent an overview of latest advances in microRNAs detection through nanomaterials-based fluorescent methods, like gold nanoparticles, silver and copper nanoclusters, graphene oxide, and magnetic silicon nanoparticles.

FORESEE: a tool for the systematic comparison of translational drug response modeling pipelines.

SUMMARY: Translational models that utilize omics data generated in in vitro studies to predict the drug efficacy of anti-cancer compounds in patients are highly distinct, which complicates the benchmarking process for new computational approaches. In reaction to this, we introduce the uniFied translatiOnal dRug rESponsE prEdiction platform FORESEE, an open-source R-package. FORESEE not only provides a uniform data format for public cell line and patient datasets, but also establishes a standardized environment for drug response prediction pipelines, incorporating various state-of-the-art pre-processing methods, model training algorithms and validation techniques. The modular implementation of individual elements of the pipeline facilitates a straightforward development of combinatorial models, which can be used to re-evaluate and improve already existing pipelines as well as to develop new ones. AVAILABILITY AND IMPLEMENTATION: FORESEE is licensed under GNU General Public License v3.0 and available at https://github.com/JRC-COMBINE/FORESEE and https://doi.org/10.17605/OSF.IO/RF6QK, and provides vignettes for documentation and application both online and in the Supplementary Files 2 and 3. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Expression Analysis of PVT1, CCDC26, and CCAT1 Long Noncoding RNAs in Acute Myeloid Leukemia Patients.

BACKGROUND: Recent evidence indicates that the PVT1, CCDC26, and CCAT1 long noncoding RNAs (lncRNAs) are involved in the leukemogenic process. This study quantified the expression levels of the PVT1, CCDC26, and CCAT1 lncRNAs in patients with acute myeloid leukemia (AML) and also correlated their expression levels with the clinicopathological features of the patients. MATERIALS AND METHODS: The expression levels of the PVT1, CCDC26, and CCAT1 lncRNAs were analyzed using quantitative reverse transcription-polymerase chain reaction of bone marrow specimens obtained from 86 AML patients, 48 AML-M3 patients, and 40 normal controls. RESULTS: No differences were found between the combined AML patient populations and the healthy controls with respect to the expression levels of PVT1, CCDC26, and CCAT1 (p = 0.35, p = 0.09, and p = 0.77, respectively). However, compared with the controls, the AML-M3 patients had higher PVT1 expression (p = 0.017). Furthermore, high-risk AML-M3 patients manifested higher expression levels of PVT1 than low- and intermediate-risk groups. In addition, distinctive CCDC26 and CCAT1 expression levels were observed among patients with different French-American-British subtypes (p = 0.001 for CCDC26 and p = 0.013 for CCAT1). Compared with the healthy controls, AML-M4 and M5 had higher CCAT1 expression (p = 0.04) and AML-M2 and AML-M4/M5 patients had higher CCDC26 expression (p < 0.001 and p = 0.02, respectively). In addition, different patterns of CCDC26 expression were found among the different cytogenetic risk subtypes (p = 0.005). Finally, patients with intermediate cytogenetic risk showed higher CCDC26 expression levels. CONCLUSION: The differential expression of the PVT1, CCDC26, and CCAT1 lncRNAs in different AML subtypes suggests that the deregulation of these transcripts may function in the multistep leukemogenic process and that they may serve as new therapeutic targets for this malignancy.

Low Expression of Long Noncoding RNA IRAIN Is Associated with Poor Prognosis in Non-M3 Acute Myeloid Leukemia Patients.

AIMS: Deregulation of the long noncoding RNA IRAIN has been identified in several cancers. However, the expression pattern of IRAIN and its clinical implication in acute myeloid leukemia (AML) are unknown. The purpose of this study was to investigate the expression status of IRAIN and its clinical significance in non-M3 AML patients. METHODS: Quantitative reverse transcription-polymerase chain reaction was performed to examine IRAIN transcript levels in 64 de novo non-M3 AML patients and 51 healthy controls. The association of IRAIN expression with clinicopathological factors was statistically analyzed. RESULTS: Compared with the controls, IRAIN was significantly downregulated in non-M3 AML patients (p < 0.001). The median of IRAIN expression divided the non-M3 AML patients into IRAIN low-expressing (IRAINlow) and IRAIN high-expressing (IRAINhigh) groups. The IRAINlow group tended to have higher white blood cell count and blast counts and had markedly shorter overall survival (OS) and relapse-free survival (RFS) (p = 0.044 and 0.009, respectively). In addition, patients with refractory response to chemotherapies and those with subsequent relapse had lower initial IRAIN expression. Multivariate analysis further identified IRAIN transcript levels as an independent prognostic factor for both RFS and OS. CONCLUSIONS: Our finding suggests that IRAIN transcript levels may be a useful biomarker for the prognosis of non-M3 AML patients.

Up-regulation of miR-21 decreases chemotherapeutic effect of dendrosomal curcumin in breast cancer cells.

OBJECTIVES: Despite the good results of anticancer activities by curcumin, there are some hurdles that limit the use of curcumin as an anticancer agent. Many methods were examined to overcome this defect like the use of the dendrosomal curcumin (DNC). There is increasing evidence that miRNAs play important roles in biological processes. In this study, we focus on the roles of microRNA-21 in the anti-cancer effects of DNC in breast cancer. MATERIALS AND METHODS: Also, we have used different methods such as MTT, apoptosis, cell cycle analysis, transwell migration assay and RT-PCR to find out more. RESULTS: We observed that miR-21 decreased apoptotic cells in both cells (from 6.35% to 0.34 % and from 7.72% to 1.32% orderly) and DNC increased it. As well as, our findings indicated that cell migration capacity was increased by miR-21 over expression and was decreased by DNC. The combination of miR-21 vector transfection and DNC treatment showed lower percentage of apoptotic cells or a higher level of penetration through the membrane compared with DNC treatment alone. Furthermore, DNC induced a marked increase in the number of cells in sub G1/G1 phase and a decrease in G2/M phase of the cell cycle in both; but, we observed reverse results compared it, after transfection with miR-21 vector. CONCLUSION: We observed that miR-21 suppress many aspects of anti-cancer effects of DNC in breast cancer cells, it seems that co-treatment with DNC and mir-21 down-regulation may provide a clinically useful tool for drug-resistance breast cancer cells.

Antiproliferative and Apoptotic Effect of Dendrosomal Curcumin Nanoformulation in P53 Mutant and Wide-Type Cancer Cell Lines.

OBJECTIVE: The aim of this paper is to investigate the effect of dendrosomal curcumin (DNC) on the expression of p53 in both p53 mutant cell lines SKBR3/SW480 and p53 wild-type MCF7/HCT116 in both RNA and protein levels. BACKGROUND: Curcumin, derived from Curcumin longa, is recently considered in cancer related researches for its cell growth inhibition properties. p53 is a common tumor-suppressor gene involved in cancers and its mutation not only inhibits tumor suppressor activity but also promotes oncogenic activity. METHOD: Here, p53 mutant/Wild-type cells were employed to study the toxicity of DNC using MTT assay, Flow cytometry and Annexin-V, Real-time PCR and Western blot were used to analyze p53, BAX, Bcl-2, p21 and Noxa changes after treatment. RESULTS: During the time, DNC increased the SubG1 cells and decreased G1, S and G2/M cells, early apoptosis also indicated the inhibition of cell growth in early phase. Real-Time PCR assay showed an increased mRNA of BAX, Noxa and p21 during the time with decreased Bcl-2. The expression of p53 mutant decreased in SKBR3/SW480, and the expression of p53 wild-type increased in MCF7/HCT116. CONCLUSION: Consequently, p53 plays an important role in mediating the survival by DNC, which can prevent tumor cell growth by modulating the expression of genes involved in apoptosis and proliferation.

Dendrosomal curcumin nanoformulation modulate apoptosis-related genes and protein expression in hepatocarcinoma cell lines.

The side-effects observed in conventional therapies have made them unpromising in curing Hepatocellular carcinoma; therefore, developing novel treatments can be an overwhelming significance. One of such novel agents is curcumin which can induce apoptosis in various cancerous cells, however, its poor solubility is restricted its application. To overcome this issue, this paper employed dendrosomal curcumin (DNC) was employed to in prevent hepatocarcinoma in both RNA and protein levels. Hepatocarcinoma cells, p53 wild-type HepG2 and p53 mutant Huh7, were treated with DNC and investigated for toxicity study using MTT assay. Cell cycle distribution and apoptosis were analyzed using Flow-cytometry and Annexin-V-FLUOS/PI staining. Real-time PCR and Western blot were employed to analyze p53, BAX, Bcl-2, p21 and Noxa in DNC-treated cells. DNC inhibited the growth in the form of time-dependent manner, while the carrier alone was not toxic to the cell. Flow-cytometry data showed the constant concentration of 20µM DNC during the time significantly increases cell population in SubG1 phase. Annexin-V-PI test showed curcumin-induced apoptosis was enhanced in Huh7 as well as HepG2, compared to untreated cells. Followed by treatment, mRNA expression of p21, BAX, and Noxa increased, while the expression of Bcl-2 decreased, and unlike HepG2, Huh7 showed down-regulation of p53. In summary, DNC-treated hepatocellular carcinoma cells undergo apoptosis by changing the expression of genes involved in the apoptosis and proliferation processes. These findings suggest that DNC, as a plant-originated therapeutic agent, could be applied in cancer treatment.

Combined Population Dynamics and Entropy Modelling Supports Patient Stratification in Chronic Myeloid Leukemia.

Modelling the parameters of multistep carcinogenesis is key for a better understanding of cancer progression, biomarker identification and the design of individualized therapies. Using chronic myeloid leukemia (CML) as a paradigm for hierarchical disease evolution we show that combined population dynamic modelling and CML patient biopsy genomic analysis enables patient stratification at unprecedented resolution. Linking CD34(+) similarity as a disease progression marker to patient-derived gene expression entropy separated established CML progression stages and uncovered additional heterogeneity within disease stages. Importantly, our patient data informed model enables quantitative approximation of individual patients' disease history within chronic phase (CP) and significantly separates "early" from "late" CP. Our findings provide a novel rationale for personalized and genome-informed disease progression risk assessment that is independent and complementary to conventional measures of CML disease burden and prognosis.

The effect of Se salts on DNA structure.

There is considerable interest in the role of selenium in cancer prevention. Various organic and inorganic Se compounds are considered to be antioxidants. In the present study, the binding modes, the binding constants and the stability of Se-DNA complexes have been determined by Fourier transform infrared (FTIR) and UV-Visible spectroscopic methods. Spectroscopic evidence showed that Na(2)SeO(4) and Na(2)SeO(3) bind to the minor and major grooves of DNA and the backbone phosphate (PO(2)) with overall binding constants of K(Na(2)SeO(4)-DNA)=5.20×10(4) M(-1) and K(Na(2)SeO(3)-DNA)=1.87×10(3) M(-1). DNA aggregations occurred at high selenium concentrations. No biopolymer conformational changes were observed upon Na(2)SeO(3) and Na(2)SeO(4) interactions, while DNA remained in the B-family structure.