Evaluation of expression level of BANCR, MALAT1 and FER1L4 and their target genes in coumarin-treated AGS cell line.

Because long non-coding RNAs (lncRNAs) can affect several interconnected processes, its value as a predictive marker for gastric cancer has been demonstrated. Coumarin - a natural compound known to contain some beneficial antitumor qualities - was tested for its effects on AGS gastric cancer cells. In this study, we investigated the expression level of selected cellular lncRNAs (BANCR, MALAT1 and FER1L4) and their target genes (PTEN, p-PI3K and p-AKT) in coumarin-treated AGS cell line. The expressions of the three lncRNAs: BANCR, MALAT1 and FER1L4, as well as their specified targets, PTEN, PI3K and AKT, were measured by qRT-PCR. To gauge the impact of coumarin on the AGS cells, a MTT assay was utilized. A Western blot has been employed to assess variations in PTEN, p-PI3K, and p-AKT expression. The experiment's results showed that AGS viability diminished with increasing doses of coumarin. Compared to the control cells, the cells exposed to coumarin had showed reduced levels of mRNAs which are known targets of the lncRNA BANCR. At the same time, levels of lncRNAs MALAT1 and FER1L4 within coumarin group have been higher comparing to those within control group. Additionally, the Western blot analysis revealed that the coumarin-treated cells expressed lower levels of p-PI3K, PTEN as well as p-AKT compared to control group. This information points to coumarin being a possible option in a treatment regimen for gastric cancer due to its ability to affect lncRNAs and the molecules they target.

Nanoemulsion and nanoencapsulation of a hydroethanolic extract of Nettle (Urtica dioica) and Wormwood (Artemisia absinthium): comparison of antibacterial and anticancer activity.

Introduction: Nanoemulsion and nanoencapsulation are attractive novel methods that can be used for incorporating active plant extracts in food preparations and pharmaceutical formulations. In the current study, we aimed to investigate the anticancer and antibacterial effects of hydroethanolic extracts of Nettle (NE), Wormwood (WE), and the combination of the two plants (CNWE), as well as their nanoemulsion forms (NN, NW, CNNW) and nanoencapsulation forms (CN, CW, and CCNW). Methods: The morphology and structure of the nanoemulsion and nanoencapsulation preparations were assessed utilizing dynamic light scattering (DLS) along with transmission electron microscopy (TEM). The antibacterial activity of the prepared formulations were assessed by determining minimum inhibitory concentration (MIC), zone of inhibition diameter, minimum bactericidal concentration (MBC), along with biofilm growth inhibition against Salmonaella typhimurium and Klebsiella. pneumoniae. The anticancer activity was evaluated via a MTT assay in the colon cancer cell line (HCT116). Results: The nanoemulsion and nanoencapsulation particle size varied between 10 and 50 nm and 60 and 110 nm, respectively. The MIC values were between 11.25 and 95 µg/mL along with MBC values between 11.25 and 190 µg/mL. The highest inhibition of biofilm formation was observed with CCNW against K. pneumoniae (∼78.5%) and S. typhimurium (∼73%). In descending order, the inhibition of biofilm formation was CCNW > CW > CN > CNNW > NN > NW > CNWE > NE > WE against the tested bacteria. The IC50 values for NE, WE, CNWE, NN, NW, CNNW, CN, CW, and CCNW were determined as 250, 170, 560, 380, 312, 370, 250, 420, and 700 µg/mL, respectively. Exposure to a high concentration of NW resulted in a significantly lower HCT116 viability compared to other groups. Taken together, CNNW, and CCNW showed the highest antibacterial and anticancer activitiy. Discussion: Nanoemulsion and nanoencapsulation were effective ways to increase the antibacterial and anticancer activity of the extracts and could be used in the food and pharmaceutical industries.

The Combination of 5-FU and Resveratrol Can Suppress the Growth of Glioblastoma Cells Through Downregulation of TRPM2 and ß-Catenin.

Glioblastoma multiforme (GBM) is the most common as well as the most fatal primary malignant tumor of the central nervous system (CNS), which still lacks a definitive cure. 5-FU is an anti-metabolite anti-cancer agent which has shown promising results for GBM treatment. Resveratrol (Res) is a phytochemical anti-oxidant that has also been effective in suppressing the progression of GBM. The combination of 5-FU and Res has been studied in a variety of cancers, but no study has assessed this combination in GBM. In this study, we investigated how 5-FU and Res, in combination and alone, may affect the growth and apoptosis of GBM cells and also the potential of TRPM2 and ß-catenin as the mediator of their effects. U87 cells were cultured as the in vitro model. MTT assay was used for measuring cellular growth, and RT-qPCR was used to measure the level of caspase-3, TRPM2, and ß-catenin; caspase-3 level served as the indicator of apoptotic rate. 5-FU and Res, in combination and alone, suppressed the growth while promoting the apoptosis of U87 cells; these effects were significantly greater when they were used in combination. RT-qPCR showed downregulation of TRPM-2 and ß-catenin in response to this combination, which suggested that these two molecules may mediate the cited anti-oncogenic effects. In conclusion, our study confirmed the synergism between 5-FU and Res in suppressing the progression of GBM and suggested the putative axis of TRPM2/ ß-catenin as the downstream mediator of this therapeutic regime. Future studies may be able to approve the eligibility of this therapeutic regime for GBM treatment and also the underlying mechanism.

Doxorubicin-loaded zymosan nanoparticles: Synergistic cytotoxicity and modulation of apoptosis and Wnt/ß-catenin signaling pathway in C26 colorectal cancer cells.

Zymosan is a ß-glucan isolated from Saccharomyces cerevisiae that could be employed for drug delivery. We synthesized zymosan nanoparticles and measured their structural and morphological properties using XRD, UV-Vis spectroscopy, TEM and AFM. The loading of doxorubicin (DOX) onto the nanoparticles was confirmed by FT-IR, and the DOX release was shown to be pH-dependent. The effect of these agents on C26 cell viability was evaluated by MTT tests and the expression of genes connected with the Wnt/ß-catenin pathway and apoptosis were analyzed by RT-qPCR and Western blotting. Treatments were able to suppress the proliferation of C26 cells, and the zymosan nanocarriers loaded with DOX enhanced the anti-proliferative effect of DOX in a synergistic manner. Zymosan nanoparticles were able to suppress the expression of cyclin D1, VEGF, ZEB1, and Twist mRNAs. Treatment groups upregulated the expression of caspase-8, while reducing the Bax/Bcl-2 ratio, thus promoting apoptosis. In conclusion, zymosan nanoparticles as DOX nanocarriers could provide a more targeted drug delivery through pH-responsiveness, and showed synergistic cytotoxicity by modifying Wnt/ß-catenin signaling and apoptosis.

Expression of selected long non-coding RNAs in gastric cancer cells treated with coumarin: Possible mechanisms for anti-cancer activity.

Long non-coding RNAs (lncRNAs) can be utilized as prognostic indicators of gastric cancer since they can affect several cancer-related processes. Coumarin is a natural product with some useful anti-cancer properties. Here, we measured the expression of selected lncRNAs (RuPAR, SNHG6, CASC11, and their targets, miR-340-5p, p21, E-cadherin, and CDK1) in AGS gastric cancer cells treated with coumarin. MTT test has been utilized for assessing the AGS cells' cell viability after exposure to coumarin. The expression of the lncRNAs (RuPAR, SNHG6, and CASC11) and miR-340-5p was evaluated via qRT-PCR. Western blot analysis has been utilized to determine changes in p21, E-cadherin, and CDK1 expression. Coumarin decreased AGS viability in a dose-dependent manner. The coumarin treated cells had lower levels of the mRNAs known to be targets of lncRNAs SNHG6 and CASC11 compared to control. Additionally, the coumarin group had increased levels of lncRNA RuPAR expression when compared with the control group. Some lncRNA targets, including p21, E-cadherin, and CDK1, showed lower expression in the coumarin group compared to the control by Western blotting. Coumarin could be a promising pharmacological candidate to be included in gastric cancer treatment regimens because it modulates lncRNAs and their targets.

Metal nanoparticles as a potential technique for the diagnosis and treatment of gastrointestinal cancer: a comprehensive review.

Gastrointestinal (GI) cancer is a major health problem worldwide, and current diagnostic and therapeutic approaches are often inadequate. Various metallic nanoparticles (MNPs) have been widely studied for several biomedical applications, including cancer. They may potentially overcome the challenges associated with conventional chemotherapy and significantly impact the overall survival of GI cancer patients. Functionalized MNPs with targeted ligands provide more efficient localization of tumor energy deposition, better solubility and stability, and specific targeting properties. In addition to enhanced therapeutic efficacy, MNPs are also a diagnostic tool for molecular imaging of malignant lesions, enabling non-invasive imaging or detection of tumor-specific or tumor-associated antigens. MNP-based therapeutic systems enable simultaneous stability and solubility of encapsulated drugs and regulate the delivery of therapeutic agents directly to tumor cells, which improves therapeutic efficacy and minimizes drug toxicity and leakage into normal cells. However, metal nanoparticles have been shown to have a cytotoxic effect on cells in vitro. This can be a concern when using metal nanoparticles for cancer treatment, as they may also kill healthy cells in addition to cancer cells. In this review, we provide an overview of the current state of the field, including preparation methods of MNPs, clinical applications, and advances in their use in targeted GI cancer therapy, as well as the advantages and limitations of using metal nanoparticles for the diagnosis and treatment of gastrointestinal cancer such as potential toxicity. We also discuss potential future directions and areas for further research, including the development of novel MNP-based approaches and the optimization of existing approaches.

Prediction of blood pressure based on anthropometric measurements in adolescents.

BACKGROUND: Recently, an important health issue in children is obesity, leading to hypertension. The aim of this study was to determine association of blood pressure with anthropometric variables in adolescents. METHODS: In this study, 1992 adolescents aged 11-18 years old between 2000 and 2007 were included. Cut point of anthropometric indices of waist circumference (WC), waist-to-stature ratio (WSR) and body mass index (BMI) was identified using Youden's index. RESULTS: Cut point of BMI for identification of hypertension was 19.69, 25.5, 20.65 and 24.13 for boys at middle and high school, girls at middle and high school, respectively. This measure for WSR was 0.44, 0.50, 0.45 and 0.517 for boys at middle and high school, girls at middle and high school, respectively. Regarding WC, it was 69.50, 96.5, 65.5 and 77.5 for boys at middle and high school, girls at middle and high school, respectively. CONCLUSIONS: In middle school boys, WSR, WC and BMI are associated with DBP but by increasing age, only BMI and weight are associated with DBP. BMI is the consistent anthropometric determinant of DBP. We also observed the relationship between WSR and SBP in boys, which could be applied as a predictive measure.

The relationship between regular tea drinking and calcification of the coronary arteries.

Introduction: Coronary Atherosclerosis is the leading cause of death and disability worldwide. Atherosclerosis could be detected noninvasively by coronary calcification, measured by calcium score in CT angiography. Dietary factors are influential in the evolution of coronary plaques, and one of the most prevalent drinks is black tea. We aimed to evaluate the effects of black tea on coronary calcium scores. Methods: This cross-sectional analytical descriptive study was conducted on 200 candidates for CT angiography referred by their physician because their symptoms were suggestive of ischemia. A questionnaire was filled out for every participant, and the habit of tea drinking was asked and marked as none drinker, 1-3 cups per day and >3 cups per day. Results: 89.5% of the participants consumed tea. The mean calcium score in patients who did not drink tea was 674.9±154.74 in those patients who drank 1-3 glasses per day, 269.5±46.9 and in those who drank more than three glasses of tea and was 261.1±45.2. There was a significant statistical relationship between calcium scores and tea intake, independent to other traditional risk factors (P= 0.001). Significant coronary artery plaques were also less prevalent in those who drank tea (36% and 41% in 1-3 and >3 cups, respectively) than non-drinkers (67%). Still, the number of involved vessels was not significantly different. Conclusion: Regular black tea consumption could have protective effects on coronary artery calcification.

MicroRNAs and exosomes: Cardiac stem cells in heart diseases.

Treating cardiovascular diseases with cardiac stem cells (CSCs) is a valid treatment among various stem cell-based therapies. With supplying the physiological need for cardiovascular cells as their main function, under pathological circumstances, CSCs can also reproduce the myocardial cells. Although studies have identified many of CSCs' functions, our knowledge of molecular pathways that regulate these functions is not complete enough. Either physiological or pathological studies have shown, stem cells proliferation and differentiation could be regulated by microRNAs (miRNAs). How miRNAs regulate CSC behavior is an interesting area of research that can help us study and control the function of these cells in vitro; an achievement that may be beneficial for patients with cardiovascular diseases. The secretome of stem and progenitor cells has been studied and it has been determined that exosomes are the main source of their secretion which are very small vesicles at the nanoscale and originate from endosomes, which are secreted into the extracellular space and act as key signaling organelles in intercellular communication. Mesenchymal stem cells, cardiac-derived progenitor cells, embryonic stem cells, induced pluripotent stem cells (iPSCs), and iPSC-derived cardiomyocytes release exosomes that have been shown to have cardioprotective, immunomodulatory, and reparative effects. Herein, we summarize the regulation roles of miRNAs and exosomes in cardiac stem cells.

Joint application of biochemical markers and imaging techniques in the accurate and early detection of glioblastoma.

Glioblastoma is a primary brain tumor with the most metastatic effect in adults. Despite the wide range of multidimensional treatments, tumor heterogeneity is one of the main causes of tumor spread and gives great complexity to diagnostic and therapeutic methods. Therefore, featuring noble noninvasive prognostic methods that are focused on glioblastoma heterogeneity is perceived as an urgent need. Imaging neuro-oncological biomarkers including MGMT (O6-methylguanine-DNA methyltransferase) promoter methylation status, tumor grade along with other tumor characteristics and demographic features (e.g., age) are commonly referred to during diagnostic, therapeutic and prognostic processes. Therefore, the use of new noninvasive prognostic methods focused on glioblastoma heterogeneity is considered an urgent need. Some neuronal biomarkers, including the promoter methylation status of the promoter MGMT, the characteristics and grade of the tumor, along with the patient's demographics (such as age and sex) are involved in diagnosis, treatment, and prognosis. Among the wide array of imaging techniques, magnetic resonance imaging combined with the more physiologically detailed technique of H-magnetic resonance spectroscopy can be useful in diagnosing neurological cancer patients. In addition, intracranial tumor qualitative analysis and sometimes tumor biopsies help in accurate diagnosis. This review summarizes the evidence for biochemical biomarkers being a reliable biomarker in the early detection and disease management in GBM. Moreover, we highlight the correlation between Imaging techniques and biochemical biomarkers and ask whether they can be combined.

New epigenetic players in stroke pathogenesis: From non-coding RNAs to exosomal non-coding RNAs.

Non-coding RNAs (ncRNAs) have critical role in the pathophysiology as well as recovery after ischemic stroke. ncRNAs, particularly microRNAs, and the long non-coding RNAs (lncRNAs) are critical for angiogenesis and neuroprotection, and they have been suggested to be therapeutic, diagnostic and prognostic tools in cerebrovascular diseases, including stroke. Moreover, exosomes have been considered as nanocarriers capable of transferring various cargos, such as lncRNAs and miRNAs to recipient cells, with prominent inter-cellular roles in the mediation of neuro-restorative events following strokes and neural injuries. In this review, we summarize the pathogenic role of ncRNAs and exosomal ncRNAs in the stroke.

Chitosan-Based Nanoparticles Against Viral Infections.

Viral infections, in addition to damaging host cells, can compromise the host immune system, leading to frequent relapse or long-term persistence. Viruses have the capacity to destroy the host cell while liberating their own RNA or DNA in order to replicate within additional host cells. The viral life cycle makes it challenging to develop anti-viral drugs. Nanotechnology-based approaches have been suggested to deal effectively with viral diseases, and overcome some limitations of anti-viral drugs. Nanotechnology has enabled scientists to overcome the challenges of solubility and toxicity of anti-viral drugs, and can enhance their selectivity towards viruses and virally infected cells, while preserving healthy host cells. Chitosan is a naturally occurring polymer that has been used to construct nanoparticles (NPs), which are biocompatible, biodegradable, less toxic, easy to prepare, and can function as effective drug delivery systems (DDSs). Furthermore, chitosan is Generally Recognized as Safe (GRAS) by the US Food and Drug Administration (U.S. FDA). Chitosan NPs have been used in drug delivery by the oral, ocular, pulmonary, nasal, mucosal, buccal, or vaginal routes. They have also been studied for gene delivery, vaccine delivery, and advanced cancer therapy. Multiple lines of evidence suggest that chitosan NPs could be used as new therapeutic tools against viral infections. In this review we summarize reports concerning the therapeutic potential of chitosan NPs against various viral infections.

Oxytocin improves ischemic stroke by reducing expression of excitatory amino acid transporter 3 in rat MCAO model.

Various molecular mechanisms are activated in neurons during ischemic stroke. Extracellular glutamate secretion into brain tissue causes neurotoxicity and brain damage. Excitatory amino acid transporter 3 (EAAT3) could remove the extracellular glutamate. Neuroprotective activity of oxytocin (OT) in ischemia of various tissues has been reported. This study investigates the neuroprotective effect of OT in an animal model of middle cerebral artery occlusion (MCAO) and the possible role of EAAT3. Transient MCAO was performed as a model of ischemic stroke in male rats and then OT was administrated intra-nasally. Infarct volume was measured by 2, 3, 5-triphenyl tetrazolium chloride staining. Nissl staining method was performed for the evaluation of neuronal cell morphology. Immunohistochemistry assay was performed to analyze the EAAT3 expression in the ischemic region. OT significantly reduced the infarct volume in the cerebral cortex and striatum after ischemia (P< .05). In addition, OT reduces the number of neurons with pyknotic nuclei that are significantly increased in the ischemic region (P< .01) Immunohistochemistry results showed that although EAAT3 expression increased after ischemia, OT therapy increased EAAT3 expression further (P< .05). Therefore, increased EAAT3 expression could be one of the neuroprotective mechanisms of OT after MCAO.

Cardiac complications in inherited mitochondrial diseases.

Maternally mitochondrial dysfunction includes a heterogeneous group of genetic disorders which leads to the impairment of the final common pathway of energy metabolism. Coronary heart disease and coronary venous disease are two important clinical manifestations of mitochondrial dysfunction due to abnormality in the setting of underlying pathways. Mitochondrial dysfunction can lead to cardiomyopathy, which is involved in the onset of acute cardiac and pulmonary failure. Mitochondrial diseases present other cardiac manifestations such as left ventricular noncompaction and cardiac conduction disease. Different clinical findings from mitochondrial dysfunction originate from different mtDNA mutations, and this variety of clinical symptoms poses a diagnostic challenge for cardiologists. Heart transplantation may be a good treatment, but it is not always possible, and other complications of the disease, such as mitochondrial encephalopathy, lactic acidosis, and stroke-like syndrome, should be considered. To diagnose and treat most mitochondrial disorders, careful cardiac, neurological, and molecular studies are needed. In this study, we looked at molecular genetics of MIDs and cardiac manifestations in patients with mitochondrial dysfunction.

Estrogen and progesterone attenuate glutamate neurotoxicity via regulation of EAAT3 and GLT-1 in a rat model of ischemic stroke.

OBJECTIVES: Glutamate is the most widespread neurotransmitter in the central nervous system and has several functions as a neuromodulator in the brain although in pathological conditions like ischemia it is excessively released causing cell death. Under physiological conditions, glutamate is rapidly scavenged from the synaptic cleft by excitatory amino-acid transporters (EAATs). An imbalance in glutamatergic neurotransmission could influence the expression of glutamate transporters and is a pathological feature in several neurological disorders. It has been shown that estrogen and progesterone act as neuroprotective agents after brain injury. This study aims to investigate the role of hormone therapy after middle cerebral artery occlusion (tMCAO) in the expression of GLT-1 and EAAT3 as glutamate transporters. MATERIALS AND METHODS: Middle cerebral artery occlusion technique was performed in Wistar rats in order to induce focal cerebral ischemia. Estrogen, progesterone, and a combination of both hormones were injected subcutaneously in the early minutes of reperfusion. Sensorimotor functional tests were performed and infarct volume was calculated by TTC staining of brain section. Gene and protein expression of EAAT3 and GLT-1 were evaluated by RT-PCR, immunoblotting, and immunohistochemistry. RESULTS: Behavioral scores were increased and infarct volume was reduced by hormone therapy. RT-PCR, immunoblotting, and immunohistochemistry data showed that the expression of GLT-1 and EAAT3 increased after ischemia. Also, estrogen and progesterone treatment enhanced mRNA and protein expression levels of GLT-1 and EAAT3 compared with ischemia. CONCLUSION: Steroids may protect brain tissue against ischemia-induced tissue degeneration by decreasing extracellular glutamate levels through the induction of glutamate transporters.

The therapeutic potential of resveratrol in a mouse model of melanoma lung metastasis.

Resveratrol is an anticancer phytochemical polyphenol isolated from a natural origin, without any significant side effects. Resveratrol was investigated in immunocompetent mice with regards to its possible effect on lung cancer metastasis. Cytotoxicity was assessed in three melanoma cell lines (B16F10, B6, and A375) by administration of 20 and 40 µM resveratrol. B16F10 cells were transfected with pT-tdTomato vector to express red fluorescent protein (RFP). RFP-B16F10 cells were injected IV into 3 groups of 20 C57BL/6 mice (ten for tests and others for survival). The three groups include PBS, no treatment, and resveratrol 40 mg/kg IP (4X/week for 3 weeks). Lung tissues were analyzed by TUNEL assay, Western blot, and immunohistochemistry. The in vitro growth of all melanoma cell lines was significantly suppressed by 40 µM resveratrol for 3 days. The mean survival rate of mice was enhanced and the lung tumor growth was inhibited by in vivo IP injection of 40 mg/kg resveratrol. Increased CXCL10 and IFN-γ levels and decreased angiogenesis and less tumor infiltration by Tregs were found in the lung tumors. In conclusion, lung metastasis of melanoma was effectively inhibited by resveratrol treatment.

Autophagy-related microRNAs: Possible regulatory roles and therapeutic potential in and gastrointestinal cancers.

Gastrointestinal (GI) cancers with a high incidence rate and adverse complications are associated with severe morbidity and mortality around the world. It is well recognized that early detection of the disease results in longer survival rate and better quality of life. Autophagy, an intracellular regulatory process, has been shown to play an essential role in the pathogenesis of various malignancies including GI cancers. MicroRNAs (miRNAs) are small non-coding RNAs that have regulatory functions in tumor cells and possess potential diagnostic values in early detection of cancers. It has been recently demonstrated that these molecules have modulatory effects on multiple steps of autophagy process occurring in GI malignancies. In this review, we aimed to highlight the role of autophagy-related microRNAs on GI cancer as potential targets for cancer therapy.

Nanomicellar-curcumin exerts its therapeutic effects via affecting angiogenesis, apoptosis, and T cells in a mouse model of melanoma lung metastasis.

BACKGROUND: Curcumin is a natural phytochemical polyphenol with significant anti-cancer effects and negligible side effects. In this study, the therapeutic capacity of nanomicellar-curcumin for treating lung metastasis was evaluated in an immunocompetent mouse model of metastatic melanoma. MARTIALS AND METHODS: Two doses of nanomicellar-curcumin (i.e. 10 and 20 µM) were used to induce cytotoxicity in 3 melanoma cell lines. A total of 60 mice were allocated to 20 mice in each of three groups (10 for survival and 10 for assays). Groups were no treatment control, PBS control, nanomicellar-curcumin 20 mg/kg IP 4 times a week, for three weeks). Immunohistochemistry, TUNEL assay, and Western blots were used on lung samples. RESULTS: Nanomicellar-curcumin inhibited the in vitro growth of B16 F10 melanoma cells at 20 µM over 72 h. In vivo, 20 mg/kg nanomicellar-curcumin injected IP, delayed tumor cell growth and significantly extended mouse survival rate. Tumor infiltration of regulatory T cells and angiogenesis were reduced, while IFN-γ and CXCL10 were increased. CONCLUSION: Nanomicellar-curcumin can inhibit lung metastasis and growing melanoma via activation of apoptosis, activated T cells and inhibition of angiogenesis, tumor growth and regulatory T cells.