Eupatorin and Salvigenin Potentiate Doxorubicin-Induced Apoptosis and Cell Cycle Arrest in HT-29 and SW948 Human Colon Cancer Cells

Background: Cancer persists as one of the world’s most pressing maladies. Notable points about chemotherapy are drug side effects which are almost universally encountered. Emerging knowledge focusing on mechanisms of toxicity due to chemotherapy has led to characterization of novel methods, including the exploitation of natural compounds, in combination therapies. Flavonoids are natural polyphenolic compounds that play protective roles against tumor cell development. The focus of this study was apoptotic effects of two flavonoids, eupatorin and salvigenin, in combination with doxorubicin on a cellular model of colon cancer. Method: Upon establishing a non-effective dose of doxorubicin, and effective doses of eupatorin (100μM) and salvigenin (150μM) via MTT, morphological features of apoptosis were distinguished using DAPI staining and cell cycle blockage in the sub-G1 phase. Apoptosis was determined by annexin/ PI and western blotting. ROS levels and MMP were measured to show any role of mitochondria in apoptosis. Results: Co-administration of flavonoids with doxorubicin induced apoptosis via the mitochondrial pathway as mitochondrial membrane potential and ROS production were changed. Annexin/PI analysis demonstrated that apoptosis frequency was increased with the combination treatments in colon cancer cells. Finally, the combination of these flavonoids with doxorubicin increased the Bax/Bcl-2 ratio, caspase-3 expression and PARP cleavage. Conclusion: Combination of flavonoids with doxorubicin induces apoptosis and enhances effect on cancer cells which might allow amelioration of side effects by dose lowering.     

Role of ultrasound in confirmation of endotracheal tube in neonates: a review

Tracheal intubation (TI) is a commonly done procedure in neonatal intensive care unit and delivery room during resuscitation. The confirmation of endotracheal tube (ETT) position should be done quickly as tube malposition is associated with various serious adverse outcomes like hypoxemia, right upper lobe collapse, atelectasis, air leak syndromes and esophageal intubation. ETT position can be confirmed by various methods like clinical sign, chest radiography, capnography, external digital tracheal palpation, ultrasonography (USG), respiratory function monitor, video-laryngoscope and fiberoptic devices. The current gold standard test to confirm ETT position is a chest radiograph, but it has many fallacies thus presently there is the need for a modality that helps in detection of endotracheal intubation and tube position with minimal complications. USG has been used in adult and pediatric population for detecting ETT position but there are very less studies in neonates. In this review, we analyze all the published studies, case reports and personal experiences that have sought the use of USG in neonatal population for detection of ETT position.     

Nanomaterial interactions with and trafficking across the lung alveolar epithelial barrier: implications for health effects of air-pollution particles

Studies on the health effects of air-pollution particles suggest that injury may result from inhalation of airborne ultrafine particles (<100 nm in diameter). Engineered nanomaterials (<100 nm in at least one dimension) may also be harmful if inhaled. Nanomaterials deposited on the respiratory epithelial tract are thought to cross the air-blood barrier, especially via the expansive alveolar region, into the systemic circulation to reach end organs (e.g., myocardium, liver, pancreas, kidney, and spleen). Since ambient ultrafine particles are difficult to track, studies of defined engineered nanomaterials have been used to obtain valuable information on how nanomaterials interact with and traffic across the air-blood barrier of mammalian lungs. Since specific mechanistic information on how nanomaterials interact with the lung is difficult to obtain using in vivo or ex vivo lungs due to their complex anatomy, in vitro alveolar epithelial models have been of considerable value in determining nanomaterial-lung interactions. In this review, we provide information on mechanisms underlying lung alveolar epithelial injury caused by various nanomaterials and on nanomaterial trafficking across alveolar epithelium that may lead to end-organ injury.     

Nephrogenic systemic fibrosis: a case report and review of the literature

The authors report a case of a patient who presented with thick, indurated, hyperpigmented plaques of the bilateral upper and lower extremities, ultimately discovered to be attributed to nephrogenic systemic fibrosis. The case was written to highlight the clinical manifestations of nephrogenic systemic fibrosis, as well as to make dermatologists aware of this disease, their role in diagnosis and management, and review treatment options.     

Polystyrene nanoparticle trafficking across MDCK-II

Polystyrene nanoparticles (PNP) cross rat alveolar epithelial cell monolayers via non-endocytic transcellular pathways. To evaluate epithelial cell type-specificity of PNP trafficking, we studied PNP flux across Madin Darby canine kidney cell II monolayers (MDCK-II). The effects of calcium chelation (EGTA), energy depletion (sodium azide (NaN₃) or decreased temperature), and endocytosis inhibitors methyl-β-cyclodextrin (MBC), monodansylcadaverine and dynasore were determined. Amidine-modified PNP cross MDCK-II 500 times faster than carboxylate-modified PNP. PNP flux did not increase in the presence of EGTA. PNP flux at 4°C and after treatment with NaN₃ decreased 75% and 80%, respectively. MBC exposure did not decrease PNP flux, whereas dansylcadaverine- or dynasore-treated MDCK-II exhibited ∼80% decreases in PNP flux. Confocal laser scanning microscopy revealed intracellular colocalization of PNP with clathrin heavy chain. These data indicate that PNP translocation across MDCK-II (1) occurs via clathrin-mediated endocytosis and (2) is dependent on PNP physicochemical properties. We conclude that uptake/trafficking of nanoparticles (NPs) into/across epithelia depends both on properties of the NPs and on the specific epithelial cell type.

From the Clinical Editor

This basic science study investigates the membrane translocation of polystyrene nanoparticles (PNP) via an epithelial cell monolayer utilizing canine kidney cells. The authors conclude that translocation occurs via clathrin-mediated endocytosis and is dependent on the physicochemical properties of the particular PNP.     

Sheep practice eye for ophthalmic surgery training in skills laboratory

Pig eyes are not available for surgical practice in the Middle East and Central Asia. We reviewed the literature to select an alternative animal practice eye based on biometry, availability, expense, and the ethical issue of animal sacrifice. Twenty enucleated sheep eyes were studied with an ultrasonography immersion technique, and a variety of techniques for globe harvesting were tested and compared. The sheep eye was judged to be the best practical choice for ophthalmic surgery practice and the "bone shattering" exenteration maneuver, the most efficient harvesting method. Several anterior segment procedures were performed in the sheep eyes. Introduction of this sheep model would be instrumental in the development of ophthalmology skills laboratories and surgical training in Middle Eastern and Central Asian regions. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.     

Priority interventions to improve maternal and child diets in Sub‐Saharan Africa and South Asia

Nutrition‐sensitive interventions to improve overall diet quality are increasingly needed to improve maternal and child health. This study demonstrates feasibility of a structured process to leverage local expertise in formulating programmes tailored for current circumstances in South Asia and Africa. We assembled 41 stakeholders in 2 regional workshops and followed a prespecified protocol to elicit programme designs listing the human and other resources required, the intervention's mechanism for impact on diets, target foods and nutrients, target populations, and contact information for partners needed to implement the desired programme. Via this protocol, participants described 48 distinct interventions, which we then compared against international recommendations and global goals. Local stakeholders' priorities focused on postharvest food systems to improve access to nutrient‐dense products (75% of the 48 programmes) and on production of animal sourced foods (58%), as well as education and social marketing (23%) and direct transfers to meet food needs (12.5%). Each programme included an average of 3.2 distinct elements aligned with those recommended by United Nations system agencies in the Framework for Action produced by the Second International Conference on Nutrition in 2014 and the Compendium of Actions for Nutrition developed for the Renewed Efforts Against Child Hunger initiative in 2016. Our results demonstrate that a participatory process can help local experts identify their own priorities for future investments, as a first step in a novel process of rigorous, transparent, and independent priority setting to improve diets among those at greatest risk of undernutrition.     

Accuracy of computerized automatic identification of cephalometric landmarks by a designed software

Objectives

The purpose of this study was to design software for localization of cephalometric landmarks and to evaluate its accuracy in finding landmarks.

Methods

40 digital cephalometric radiographs were randomly selected. 16 landmarks which were important in most cephalometric analyses were chosen to be identified. Three expert orthodontists manually identified landmarks twice. The mean of two measurements of each landmark was defined as the baseline landmark. The computer was then able to compare the automatic system''s estimate of a landmark with the baseline landmark. The software was designed using Delphi and Matlab programming languages. The techniques were template matching, edge enhancement and some accessory techniques.

Results

The total mean error between manually identified and automatically identified landmarks was 2.59 mm. 12.5% of landmarks had mean errors less than 1 mm. 43.75% of landmarks had mean errors less than 2 mm. The mean errors of all landmarks except the anterior nasal spine were less than 4 mm.

Conclusions

This software had significant accuracy for localization of cephalometric landmarks and could be used in future applications. It seems that the accuracy obtained with the software which was developed in this study is better than previous automated systems that have used model-based and knowledge-based approaches.