Atherosclerosis preventive effects of marrubiin against (TNF-α)-induced oxidative stress and apoptosis.

Introduction: Atherosclerosis is a complicated cascade of inflammatory processes, oxidative stress, and apoptosis, making it the most prevalent cardiovascular disease. The onset and progression of cardiovascular diseases are greatly influenced by oxidative stress. Targeting oxidative stress is an effective strategy for treating such diseases. Marrubiin is a bioactive furan labdane diterpenoid acts as a strong antioxidant to protect against oxidative damage. This study aimed to investigate the protective effects of marrubiin against oxidative stress and apoptosis in a cellular model of the vascular system. Methods: Human umbilical vein endothelial cells were treated with varying concentration of marrubiin and its IC50 value was determined. The antioxidant potential of marrubiin was assessed by measuring the intracellular level of glutathione (GSH) using a colorimetric technique. Since apoptosis plays a significant role in the plaque rupture, the study also evaluated the protective effects of marrubiin on the expression of key genes involved in apoptotic pathways. Results: Cells treated with marrubiin showed increased GSH levels compared to cell therapy control cells, indicating marrubiin's ability to counteract the effects of TNF-α's on GSH levels. Furthermore real-time PCR analysis demonstrated that marrubiin upregulated Bcl-xl while downregulating caspase3 and Nox4 in treated cells. These findings suggest that marrubiin protects against apoptosis and oxidative stress. Conclusion: Based on our findings, marrubiin is recommended as a preventive/therapeutic treatment for diseases caused by elevated intracellular reactive oxygen species levels in cardiovascular diseases.

L-Carnitine Reduced Cellular Aging of Bone Marrow Resident C-Kit+ Hematopoietic Progenitor Cells Through Telomere Dependent Pathways.

BACKGROUND: Increased oxygen species levels can induce mitochondrial DNA damage and chromosomal aberrations and cause defective stem cell differentiation, leading finally to senescence of stem cells. In recent years, several studies have reported that antioxidants can improve stem cell survival and subsequently affect the potency and differentiation of these cells. Finding factors, which reduce the senescence tendency of stem cells upon expansion, has great potential for cellular therapy in regenerative medicine. This study aimed to evaluate the effects of L-carnitine (LC) on the aging of C-kit+ hematopoietic progenitor cells (HPCs) via examining the expression of some signaling pathway components. METHODS: For this purpose, bone marrow resident C-kit+ HPCs were enriched by the magnetic-activated cell sorting (MACS) method and were characterized using flow cytometry as well as immunocytochemistry. Cells were treated with LC, and at the end of the treatment period, the cells were subjected to the realtime PCR technique along with a western blotting assay for measurement of the telomere length and assessment of protein expression, respectively. RESULTS: The results showed that 0.2 mM LC caused the elongation of the telomere length and increased the TERT protein expression. In addition, a significant increase was observed in the protein expression of p38, p53, BCL2, and p16 as key components of the telomere-dependent pathway. CONCLUSION: It can be concluded that LC can increase the telomere length as an effective factor in increasing the cell survival and maintenance of the C-kit+ HPCs via these signaling pathway components.

Bidirectional Relations Between Anxiety, Depression, and Cancer: A Review.

Epidemiological evidence continues to accumulate on the effect of stress and depression on cancer initiation and progression. Depression has been introduced as an independent predictor of increased cancer mortality. At the same time, early intervention for depression increases the survival rate. Even some evidence has given prognostic value for depression to predict cancer recurrence and mortality. This article presents current evidence on the correlations of molecular mechanisms of cancer and depression through; I. The evidence shows the role of pre-existing depression and anxiety in the development and progression of cancer. II. The Immune system performs a crucial role in stress, depression, and cancer. III. The role of stress and depression-induced inflammation. IV. The evidence has proposed that cancer may result in depression and the effect of depression on cancer outcomes. In conclusion, the importance of preventive interventions to monitor patients' mental health during cancer treatment is very significant and should not be underestimated. In other words, the initial interventions can improve depressive symptoms and increase cancer survival. On the other hand, by identifying key biomarkers of depression, physicians can identify cancer patients at risk for depression or those who may not respond to routine treatments. Revealing the molecular mechanism of the cancer microenvironment in the development of comorbidities promises innovative therapeutic options for cancer. Identifying these mechanisms opens a new avenue in identifying cancer patients at risk for depression and can also provide considerable potential in identifying depressive patients prone to cancer.

Smart chitosan-folate hybrid magnetic nanoparticles for targeted delivery of doxorubicin to osteosarcoma cells.

Chitosan (CS)-based pH-sensitive nanocomposites were fabricated for the targeted delivery of doxorubicin (DOX) to osteosarcoma cells. To prepare the nanocomposite, CS was functionalized with succinic anhydride (SA) (CS-SA). CS-folic acid (FA) conjugates were produced by the conjugation of CS with FA via an amide bond. Next, Fe3O4 magnetic nanoparticles (MNPs) ferrofluid was fabricated, and nanocomposite was produced using MNPs and synthesized CS-SA/CS-FA and CS-SA via an inclusion formation between -COOH groups of CS-SA and hydroxyl groups of Fe3O4. Finally, DOX molecules were loaded onto the nanocomposites. The nanocomposites were characterized through FT-IR, DLS, XRD, VSM, TEM, and UV-Vis spectroscopy analyses. DOX release profile at various pHs indicated an enhanced release of DOX in acidic conditions. The cytotoxicity assay demonstrated that the nanocarriers alone were cytocompatible on cells examined. The MG-63 cells, which partly express the folate receptors (FRs), particularly FR-α, showed meaningfully higher cellular uptake of the DOX-loaded CS-FA/CS-SA@MNPs than the FR-negative lung cancer A549 cells. The DOX-loaded CS-FA/CS-SA-MNPs could induce significant cytotoxicity in the MG-63 cells but not in A549 cells. Based on these findings, the DOX-loaded CS-FA/ CS-SA-MNPs might be considered a smart pH-sensitive nanosystem for the targeted delivery of anticancer agents to osteosarcoma cancer cells.

Sclareol Inhibits Hypoxia-Inducible Factor-1α Accumulation and Induces Apoptosis in Hypoxic Cancer Cells.

Purpose: The hypoxia in solid tumors is associated with the resistance to chemo/radiotherapy. Hypoxia-inducible factor-1 (HIF-1) plays a key role in cell remodeling to hypoxia. Therefore, the inhibition of HIF-1 accumulation is considered a hopeful strategy for the treatment of cancer. Here, we aimed to evaluate the geno- and cytotoxicity properties of sclareol, a natural bicyclic diterpene alcohol, on A549 cells in CoCl2-induced hypoxia. Methods: The cytotoxicity and apoptosis-inducing properties of sclareol on the A549 cell were evaluated using MTT assay and Annexin V/PI staining, respectively in hypoxia. DAPI staining, DNA ladder, and comet assay were used to evaluate the genotoxicity. Further, the qPCR technique was employed to assess the expression of HIF-1α, HIF-1ß, and downstream target genes (GluT1, and Eno1). Finally, the level of HIF-1α protein was evaluated through Western blotting in sclareol-treated cells in hypoxia. Results: The inhibitory concentration (IC50) of sclareol against A549 cells was 8 µg/mL at 48 hours in hypoxia. The genotoxicity of sclareol was confirmed in the cells treated with sclareol in hypoxia. Sclareol induced ~46% apoptosis and also necrosis in the hypoxic condition. The qPCR analyses showed an enhanced suppression of HIF-1α, HIF-1ß, GluT1, and Eno1 due to the sclareol treatment in the hypoxia. Moreover, protein quantification analysis showed dose-dependently degradation of HIF-1α in hypoxia upon treatment with sclareol. Conclusion: The results obtained here indicate that sclareol possesses dose-dependent cytotoxicity effects against A549 cells in hypoxia through inhibition of HIF-1α protein accumulation, increasing cell sensitivity to intracellular oxygen levels, and disruption of cell adaptation to hypoxia.

Recent clinical findings on the role of kinase inhibitors in COVID-19 management.

The highly pathogenic, novel coronavirus disease (COVID-19) outbreak has emerged as a once-in-a-century pandemic with poor consequences, urgently calling for new therapeutics, cures, and supportive interventions. It has already affected over 250 million people worldwide; thereby, there is a need for novel therapies to alleviate the related complications. There is a paradigm shift in developing drugs and clinical practices to combat COVID-19. Several clinical trials have been performed or are testing diverse pharmacological interventions to alleviate viral load and complications such as cytokine release storm (CRS). Kinase-inhibitors have appeared as potential antiviral agents for COVID-19 patients due to their efficacy against CRS. Combination of kinase inhibitors with other therapies can achieve more efficacy against COVID-19. Based on the pre-clinical trials, kinase inhibitors such as Janus kinase-signal transducer and activator of transcription (JAK/STAT) inhibitors, Brutton's tyrosin kinase (BTK) inhibitors, p38 mitogen-activated protein kinases (p38 MAPK) inhibitors, Glycogen synthase kinase 3 (GSK-3) inhibitors can be a promising strategy against COVID-19. Kinase inhibitors possess crucial pharmacological properties for a successful re-purposing in terms of dual anti-inflammatory and anti-viral effects. This review will address the current clinical evidence and the newest discovery regarding the application of kinase inhibitors in COVID-19. An outlook on ongoing clinical trials (clinicaltrials.gov) and unpublished data is also presented here. Besides, Kinase inhibitors' function on COVID-19-mediated CRS is discussed.

Designing robust chitosan-based hydrogels for stem cell nesting under oxidative stress.

Introduction: Hydrogels are unique candidates for a wide range of biomedical applications including drug delivery and tissue engineering. The present investigation was designed to consider the impact of chitosan-based hydrogels as a scaffold on the proliferation of human bone marrow mesenchymal stem cells (hBM-MSCs) besides neutralization of oxidative stress in hBM-MSCs. Methods: Chitosan (CS) and CS-gelatin hydrogels were fabricated through ionic crosslinking using ß-glycerophosphate. The hBM-MSCs were cultured on the prepared matrices and their proliferation was evaluated using DAPI staining and MTT assay. Furthermore, the effect of hydrogels on oxidative stress was assessed by measuring the expression of NQO1, Nrf2, and HO-1 genes using real-time PCR. Results: The developed hydrogels indicated a porous structure with high water content. The toxicity studies showed that the prepared hydrogels have a high biocompatibility/cytocompatibility. The expression of intracellular antioxidant genes was studied to ensure that stress is not imposed by the scaffold on the nested cells. The results showed that Nrf2 as a super transcription factor of antioxidant genes and its downstream antioxidant gene, NQO1 were downregulated. Unexpectedly, the upregulation of HO-1 was detected in the current study. Conclusion: The prepared CS-based hydrogels with desired properties including porous structure, high swelling ability, and cytocompatibility did not show oxidative stress for the nesting of stem cells. Therefore, they could be attractive scaffolds to support stem cells for successful tissue engineering purposes.

The impact of laughter yoga on depression and anxiety among retired women: a randomized controlled clinical trial.

Recently, laughter yoga (LY) has been introduced for managing depression and anxiety. This study aimed to investigate the impact of LY on depression and anxiety among retired women in city of Bojnurd, Iran, 2018. Sixty-six retired women were randomly assigned to intervention and control groups. Intervention group received LY twice weekly for 8 weeks; control group had their routine daily activities. Depression and anxiety levels were measured at study initiation, week 4, and week 8 in both groups. Results showed significant difference in the pattern of depression (p <.001) and anxiety (p <.001) scores within and between groups. LY could be an effective intervention in reducing depression and anxiety among retired women.

Interferon-alpha position in combating with COVID-19: A systematic review.

The newborn coronaivus disease 2019 (COVID-19) pandemic has become the foremost concern of health system worldwide. Interferon typeI (IFN-I) are among the well-known antiviruses. Hence IFN-α have gained much attention as a treatment for COVID-19 recently. To sum up the efficiency of IFN-α against COVID-19, we searched PubMed, SCOPUS, and EMBASE, from the date of genesis to the 1st of October 2020. Discharge from hospital and virus clearance considered as primary and secondary outcomes, respectively. We compared the aforementioned outcomes of patients treated with standard care protocol and the patients treated with IFN-α in addition to standard care protocol. Out of 356 identified records, 14 studies were subjected for full-text screening. Finally, a systematic review was performed with inclusion of five studies. Majority of the participants were males (ranged from 43.50% to 90.0%). We found that time of viral clearance and polymerase chain reaction negative (days) in most studies were decreased in the INF-α + standard care group. The mean days of virus's clearance in INF-α group and standard group reported 27.3 and 32.43. Likewise, the average days of hospitalization was found also lower in INF-α group (18.55 vs. 24.36). This study provides a stand to conclude that early administration of INF-α may be accounted as a promising treatment of COVID-19.

Antibacterial, Antifungal, and Antioxidant Activity of Cleome coluteoides: An In Vitro Comparative Study Between Leaves, Stems, and Flowers.

OBJECTIVES: Cleome coluteoides, which belongs to the Capparidaceae family, and has been used in folk medicine for a long time. Our research aims to measure the antioxidant, antibacterial, and antifungal activities of C. coluteoides. MATERIALS AND METHODS: Various solvents, such as ethyl acetate, methanol, and dichloromethane, were used to extract different plant parts. Antibacterial and antifungal activities were assayed by disk and well diffusion methods, and the antioxidant activity was screened by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing ability of plasma methods. RESULTS: Results showed that Gram-negative bacteria and fungus were resistant to various plant extracts. Against all Gram-positive bacteria tested, C. coluteoides' flower extract had the highest inhibition effects. Also, the most sensitive bacterium was Bacillus cereus, which had an 18-mm inhibition zone. Due to the solvent's physical and chemical properties, different C. coluteoides extracts exhibited various antioxidant activities in the antioxidant activity assay. To some extent, methanol extract of leaves showed the highest DPPH radical scavenging activity at various concentrations that ranged from 5 to 160 mg.mL-1. The methanol extract of flower was observed to have the highest level of phenolics among all tested extracts. CONCLUSION: This study demonstrates that different extracts from various C. coluteoides parts are different in their properties, therefore, a proper solvent should be used to extract maximum amounts of antioxidant and antibacterial components from a typical plant material.

Interferon-beta offers promising avenues to COVID-19 treatment: a systematic review and meta-analysis of clinical trial studies.

Severe acute respiratory syndrome coronavirus 2 principally weakens the hosts' innate immune system by impairing the interferon function and production. Type I interferons (IFNs) especially IFN-ß are best known for their antiviral activities. IFNs accompanied by the standard care protocols have opened up unique opportunities for treating the coronavirus disease 2019 (COVID-19). The databases including PubMed, SCOPUS, EMBASE, and Google Scholar were searched up to October 30, 2020. The primary and secondary outcomes were considered discharge and mortality, respectively. The abovementioned outcomes of standard care protocol were compared with the standard care plus IFN-ß in the confirmed COVID-19 patients. Out of 356 records identified, 12 randomized clinical trial studies were selected for full-text screening. Finally, 5 papers were included in the systematic review and 3 papers in the meta-analysis. The average mortality rate was reported as 6.195% and 18.02% in intervention and control groups, respectively. Likewise, the median days of hospitalization were lower in the intervention group (9 days) than the control group (12.25 days). According to meta-analysis, IFN-ß was found to increase the overall discharge rate (RR = 3.05; 95% CI: 1.09-5.01). Our findings revealed that early administration of IFN-ß in combination with antiviral drugs is a promising therapeutic strategy against COVID-19.

What Happens to Patients with Bipolar Disorder after Bariatric Surgery? A Review.

Bipolar disorder (BD) patients are at high risk of obesity, which affects their quality of life (QOL). Since there is a high comorbidity between BD and obesity, most BD patients seek surgical intervention for obesity. Nowadays, bariatric surgery (BS) is considered appropriate for carefully selected patients with BD. Evaluations before performing BS and careful follow-up of patients with the bipolar spectrum are highly recommended. This study reviews the effects of BS on the course of BD and, at the same time, assesses the effect of BD on the consequences of the surgery. Our results showed that the number of studies approving the promising impact of surgery on BD was more than those disapproving it. However, more accurate results require more than 3-year follow-ups.

Oxidized cholesterol exacerbates toll-like receptor 4 expression and activity in the hearts of rats with myocardial infarction.

Introduction: The present study examined the effects of high cholesterol and high oxidized-cholesterol diets on the myocardial expression of TLR4 and pro-inflammatory cytokine in rats. Methods: Male Wistar rats were allocated into 6 groups and fed with a normal diet, cholesterol, and oxidized-cholesterol rich diets with or without isoproterenol-induced myocardial infarction. TLR4 and MyD 88 expression and levels tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) were measured in the heart and serum. Results: Oxidized cholesterol-fed animals had higher serum levels of oxidized low-density lipoprotein (LDL) (263 ± 13 ng/dL) than the cholesterol-fed animals (98 ± 8 ng/dL; P < 0.001). A high level of oxidized-LDL caused fibrotic cell formation and enhanced neutrophil infiltration in the absence of MI. Both cholesterol and oxidized-cholesterol upregulated TLR4 mRNA expression and increased TNF-α and IL-6 production in the hearts of rats with MI. In rats fed with oxidized-cholesterol the serum and myocardial levels of TNF-α (653 ± 42 pg/mL, 1375 ± 121 pg/100 mg, respectively) were higher than MI group (358±24 pg/mL, P < 0.001 and 885 ± 56 pg/100 mg, P < 0.01). A significant correlation was seen between TLR4 expression and infarct size. Conclusion: These findings suggest that cardiac TLR4 is preferentially upregulated by oxidized cholesterol in rats. Oxidized cholesterol may have a critical role in cardiac toxicity in the absence of pathological conditions.

Combating atherosclerosis with targeted nanomedicines: recent advances and future prospective.

Introduction: Cardiovascular diseases (CVDs) is recognized as the leading cause of mortality worldwide. The increasing prevalence of such disease demands novel therapeutic and diagnostic approaches to overcome associated clinical/social issues. Recent advances in nanotechnology and biological sciences have provided intriguing insights to employ targeted Nanomachines to the desired location as imaging, diagnosis, and therapeutic modalities. Nanomedicines as novel tools for enhanced drug delivery, imaging, and diagnosis strategies have shown great promise to combat cardiovascular diseases. Methods: In the current study, we intend to review the most recent studies on the nano-based strategies for improved management of CVDs. Results: A cascade of events results in the formation of atheromatous plaque and arterial stenosis. Furthermore, recent studies have shown that nanomedicines have displayed unique functionalities and provided de novo applications in the diagnosis and treatment of atherosclerosis. Conclusion: Despite some limitations, nanomedicines hold considerable potential in the prevention, diagnosis, and treatment of various ailments including atherosclerosis. Fewer side effects, amenable physicochemical properties and multi-potential application of such nano-systems are recognized through various investigations. Therefore, it is strongly believed that with targeted drug delivery to atherosclerotic lesions and plaque, management of onset and progression of disease would be more efficient than classical treatment modalities.

Marrubiin-loaded solid lipid nanoparticles' impact on TNF-α treated umbilical vein endothelial cells: A study for cardioprotective effect.

Oxidative stress possesses a key role in the onset and development of cardiovascular diseases (CVDs), thus it can be an efficient target to tackle such ailment. Marrubiin, a bioactive diterpene, is a potent antioxidant against oxidative stress. Herein, we aimed to formulate marrubiin loaded solid lipid nanoparticles (SLNs) to improve its pharmacokinetics and bioavailability and also to investigate free drug and formulation's protective impact against intracellular reactive oxygen species (ROS) generation in HUVECs. Marrubiin-SLNs were formulated using hot homogenization/solidification method and then were subjected to physicochemical characterizations, i.e. size, zeta potential, morphology, polydispersity index (PDI), encapsulation efficiency (% EE), drug loading/content and physical stability assessments. MTT assay was performed to study the cytotoxicity of the intact and SLN incorporated marrubiin on HUVECs. Further, the antioxidant property of marrubiin and formulations was evaluated using DPPH radical scavenging assay and their protective effect against TNF-α induced oxidative stress was assessed by the means of intracellular ROS assessment, and also apoptosis/necrosis, cell cycle, and DNA fragmentation assays. Electron microscopy analysis showed spherical monodispersed SLNs with the size less than 100 nm, particle/zeta size analyses also approved the size of particles with a zeta potential of -1.28 ±â€¯0.17 mV. Results also showed high EE (98%), drug loading (31.74 mg/g) with 3.15% drug content. In vitro release studies revealed about 90% of marrubiin cumulative release during 24 h. The stability of marrubiin-SLNs in terms of size, zeta potential, polydispersity index, EE and drug leakage was approved. Marrubiin antioxidant stability after formulation was approved by DPPH analysis. MTT cell survival assay showed no significant cytotoxicity after 24 h and 48 h. Intracellular ROS detection assay revealed that marrubiin and marrubiin-SLNs, play protective effect against TNF-α induced oxidative stress in HUVECs which was further approved by apoptosis assessment. Conclusively, based on our findings, marrubiin nanoparticles are proposed as a preventive/therapeutic remedy against disorders elicited by increased levels of intracellular ROS in CVDs.

Evaluation of Antibacterial Efficacy of Photodynamic Therapy vs. 2.5% NaOCl against E. faecalis-infected Root Canals Using Real-time PCR Technique.

BACKGROUND: Bacteria like E. faecalis can produce intra- and extra-radicular biofilms. Theoretically, the adjustable penetration ability of lasers enables better access to root canal system. Therefore the aim of the present study was to compare the ability of photoactivated laser and 2.5% NaOCl irrigation solution to eliminate E. faecalis from the root canals by real-time PCR technique. MATERIAL AND METHODS: Sixty extracted human upper central incisors were selected and sterilized in an autoclave. The root canals were infected with E. faecalis (PTCC 1237, Persian Type Culture Collection, Iran) and then incubated for 24 hours. The samples were randomly divided into 3 groups. No intervention was made in the control group (group 1). In group 2, laser therapy was performed with a power of 100 mW by diode laser for 120 seconds. In group 3, the canals were irrigated with 5 mL of 2.5% NaOCl; then all the samples were sonicated in 15 mL of normal saline in test tubes in order to isolate the bacteria. DNA extraction was performed followed by real-time PCR technique for all the samples. RESULTS: Inhibition of bacterial growth in all the experimental samples was significantly more than that in the control group. There was a significant difference between photodynamic therapy and 2.5% NaOCl. The effect of NaOCl in all the samples was better than photodynamic therapy. The results of the mean CT (cyclic threshold) were 40, 30.2 and 15.35 for 2.5% NaOCl, photodynamic therapy and control group, respectively. CONCLUSIONS: Based on the results of this experimental study, 2.5% NaOCl eliminated E. faecalis from infected root canals more effectively compared to photodynamic therapy. Key words:Photoactivated laser, Enterococcus faecalis, antibacterial agents, sodium hypochlorite.

Lipopolysaccharide Induced Activation of Toll Like Receptor 4 in Isolated Rat Heart Suggests a Local Immune Response in Myocardium.

BACKGROUND: Myocardial dysfunction is one of the major complications in patients with sepsis where there is a relationship between the blood level of cytokines and the onset of myocardial depression. In many cases of sepsis, the presence of Lipopolysaccharide (LPS) has been established. LPS Binding Protein (LBP) bound endotoxin is recognized by CD14/toll-like receptor-4 (TLR4) complexes in innate immune cells which stimulates TNF-α release. OBJECTIVES: To investigate whether isolated rat heart is capable of producing TNF-α locally through TLR4 activation by LPS. METHODS: Using langendorff method, LPS in 120 mL of the modified Krebs-Henseleit buffer solution (KHBS) at final concentration of 1 µg/mL was perfused at recycling mode. The effect of LPS on cardiac function was evaluated. To assess the TLR4 activity and TNF-α release, western blotting, real time-PCR, and ELISA were used. RESULTS: Compared with control, coronary perfusion pressure (CPP) as well as left ventricular developed pressure (LVDP), maximum and minimum rates of the left ventricular developed pressure (dP/dtmax; dP/dtmin; p<0.001) were depressed to a maximum level after 180 minutes recycling with LPS. This myocardial depression was associated with a significant increase in TLR4 expression (p<0.01), MyD88 activity (p<0.01) and TNF-α (p<0.05) concentration in the heart tissue. CONCLUSION: The results of this study show that heart is capable of producing TNF-α through TLR4 and MyD88 activation independent of classic immune system and suggest a local immune response.

Erratum: Erratum to: Impacts of Nanomedicines in Ocular Pharmacotherapy.

[This corrects the article DOI: 10.5681/bi.2011.003.].

Impacts of nanomedicines in ocular pharmacotherapy.

INTRODUCTION: The integrity of the cells/tissues in anterior and/or posterior segments of the eye plays a crucial role in biofunctions of the vision. To maintain ocular homeostasis, selective restrictiveness of the ophthalmic membranes and barriers control must act on shuttling of biomolecules. Thus, not all attempts to apply de novo nanotechnology approaches for ocular pharmacotherapy have met with the same successes as those cited here in this review, and sometimes these novel technologies tools provoke a great deal of challenges and hurdles mainly because of functional presence of these barriers. METHODS: Recent published articles related to applications of ocular nanomedicines were reviewed and highlighted in this review article. RESULTS: It seems the emergence of nanomedicines have arisen great hopes for ophthalmic pharmacotherapy, in which nanostructured medicines are expected to be able to cross the restrictive barriers of the eye. Although such fast inauguration of ocular nanomedicines will literally convey new challenges in the regulatory and translational processes, it will also grant a prolific platform from which many exciting, and yet unimagined, applications of biomedical nanotechnology will emerge for pharmacotherapy of the eye. CONCLUSION: This review provides recent advancements on ocular nanomedicines.

Gap junctions: the claymore for cancerous cells.

INTRODUCTION: Gap junctions play an important role in the cell proliferation in mammalian cells as well as carcinogenesis. However, there are controversial issues about their role in cancer pathogenesis. This study was designed to evaluate genotoxicity and cytotoxicity of Carbenoxolone (CBX) as a prototype of inter-cellular gap junction blocker in MCF7 and BT20 human breast cancer cells. METHODS: The MCF7and BT20 human breast cancer cell lines were cultivated, and treated at designated confluency with different doses of CBX. Cellular cytotoxicity was examined using standard colorimetric assay associated with cell viability tests. Gene expression evaluation was carried out using real time polymerase chain reaction (PCR). RESULTS: MCF7 and BT20 cells were significantly affected by CBX in a dose dependent manner in cell viability assays. Despite varying expression of genes, down regulation of pro- and anti-apoptotic genes was observed in these cells. CONCLUSION: Based upon this investigation, it can be concluded that CBX could affect both low and high proliferative types of breast cancer cell lines and disproportionate down regulation of both pre- and anti-apoptotic genes may be related to interacting biomolecules, perhaps via gap junctions.