Synthetic rescue of Xeroderma Pigmentosum C phenotype via PIK3C3 downregulation.

Xeroderma Pigmentosum C is a dermal hereditary disease caused by a mutation in the DNA damage recognition protein XPC that belongs to the Nucleotide excision repair pathway. XPC patients display heightened sensitivity to light and an inability to mend DNA damage caused by UV radiation, resulting in the accumulation of lesions that can transform into mutations and eventually lead to cancer. To address this issue, we conducted a screening of siRNAs targeting human kinases, given their involvement in various DNA repair pathways, aiming to restore normal cellular behavior.

Organ-On-A-Chip Devices: Technology Progress and Challenges.

Organ-On-a-Chip (OOC) is a multichannel 3D-microfluidic cell-culture system incorporated in a chip that simulates the behavior of an organ. This technology relies on a multidisciplinary science that benefits from and contributes in the progress of many fields including microbiology, microfluidics, biomaterials, and bioengineering. This review article summarizes the progress and achievements of various organ-on-chip technologies.

Exposure to emulsified isoflurane and sevoflurane protects canine primary hepatocytes against hypoxia-induced apoptosis.

Objective: Emulsified isoflurane and sevoflurane have immunomodulating and anti-inflammatory effects in vital organs such as the brain, myocardium, and kidneys subjected to ischemia-reperfusion injury. This study aims to investigate the cellular protective effects of both emulsified anesthetics in cultured canine hepatocytes.

Procedures: We analyzed the apoptosis and viability responses of cultured primary canine hepatocytes exposed to 1% O2 for 30 versus 120 minutes after being treated with emulsified isoflurane or sevoflurane in 10% lipid, or 10% lipid alone or no-treatment control at 24 hours of reoxygenation (21% O2).

Mechanical stress shapes the cancer cell response to neddylation inhibition.

Background: The inhibition of neddylation by the preclinical drug MLN4924 represents a new strategy to combat cancer. However, despite being effective against hematologic malignancies, its success in solid tumors, where cell-cell and cell-ECM interactions play essential roles, remains elusive.

Methods: Here, we studied the effects of MLN4924 on cell growth, migration and invasion in cultured prostate cancer cells and in disease-relevant prostate tumoroids.

Immune Checkpoint Inhibition in GBM Primed with Radiation by Engineered Extracellular Vesicles.

The lack of safe and effective delivery across the blood-brain barrier and the profound immune suppressive microenvironment are two main hurdles to glioblastoma (GBM) therapies. Extracellular vesicles (EVs) have been used as therapeutic delivery vehicles to GBM but with limited efficacy. We hypothesized that EV delivery to GBM can be enhanced by (i) modifying the EV surface with a brain-tumor-targeting cyclic RGDyK peptide (RGD-EV) and (ii) using bursts of radiation for enhanced accumulation.

Therapeutic siRNAs Targeting the JAK/STAT Signalling Pathway in Inflammatory Bowel Diseases.

Background And Aims: Inflammatory bowel diseases are highly debilitating conditions that require constant monitoring and life-long medication. Current treatments are focused on systemic administration of immunomodulatory drugs, but they have a broad range of undesirable side-effects. RNA interference is a highly specific endogenous mechanism that regulates the expression of the gene at the transcript level, which can be repurposed using exogenous short interfering RNA [siRNA] to repress expression of the target gene.

A new ultradian rhythm in mammalian cell dry mass observed by holography.

We have discovered a new 4 h ultradian rhythm that occurs during the interphase of the cell cycle in a wide range of individual mammalian cells, including both primary and transformed cells. The rhythm was detected by holographic lens-free microscopy that follows the histories of the dry mass of thousands of single live cells simultaneously, each at a resolution of five minutes. It was vital that the rhythm was observed in inherently heterogeneous cell populations, thus eliminating synchronization and labeling bias.

High-Content Monitoring of Drug Effects in a 3D Spheroid Model.

A recent decline in the discovery of novel medications challenges the widespread use of 2D monolayer cell assays in the drug discovery process. As a result, the need for more appropriate cellular models of human physiology and disease has renewed the interest in spheroid 3D culture as a pertinent model for drug screening. However, despite technological progress that has significantly simplified spheroid production and analysis, the seeming complexity of the 3D approach has delayed its adoption in many laboratories.

Mercury health risk assessment among a young adult Lebanese population.

Mercury (Hg) exposure represents a significant public health concern at a global level. This study aims at assessing Hg exposure and risk among Lebanese young adults based on Hg biomonitoring and seafood intake. A group of 166 young adults were administered a questionnaire to assess Hg exposure and were asked to provide a hair sample.

Distinct outcomes of CRL-Nedd8 pathway inhibition reveal cancer cell plasticity.

Inhibition of protein degradation by blocking Cullin-RING E3 ligases (CRLs) is a new approach in cancer therapy though of unknown risk because CRL inhibition may stabilize both oncoproteins and tumor suppressors. Probing CRLs in prostate cancer cells revealed a remarkable plasticity of cells with TMPRSS2-ERG translocation. CRL suppression by chemical inhibition or knockdown of RING component RBX1 led to reversible G0/G1 cell cycle arrest that prevented cell apoptosis.

Φ-score: A cell-to-cell phenotypic scoring method for sensitive and selective hit discovery in cell-based assays.

Phenotypic screening monitors phenotypic changes induced by perturbations, including those generated by drugs or RNA interference. Currently-used methods for scoring screen hits have proven to be problematic, particularly when applied to physiologically relevant conditions such as low cell numbers or inefficient transfection. Here, we describe the Φ-score, which is a novel scoring method for the identification of phenotypic modifiers or hits in cell-based screens.

A statistically inferred microRNA network identifies breast cancer target miR-940 as an actin cytoskeleton regulator.

MiRNAs are key regulators of gene expression. By binding to many genes, they create a complex network of gene co-regulation. Here, using a network-based approach, we identified miRNA hub groups by their close connections and common targets.

Continuous microcarrier-based cell culture in a benchtop microfluidic bioreactor.

Microfluidic bioreactors are expected to impact cell therapy and biopharmaceutical production due to their ability to control cellular microenvironments. This work presents a novel approach for continuous cell culture in a microfluidic system. Microcarriers (i.

The modulation of attachment, growth and morphology of cancerous prostate cells by polyelectrolyte nanofilms.

The behaviour of cancerous epithelial prostatic cells (PC3) growing on polyelectrolytes (PE) coatings was compared to the behaviour of immortalized normal prostatic cells (PNT-2). The cell behaviour was evaluated and quantified in terms of initial cell attachment, growth, metabolic activity, morphometry, adhesion, apoptosis and stress related gene expression. Both the anionic PSS (poly(sodium 4-styrenesulphonate))-terminated surface and cationic PAH (poly(allylamine hydrochloride))-terminated surfaces were not cytotoxic.

The miR-17 family links p63 protein to MAPK signaling to promote the onset of human keratinocyte differentiation.

The p63 protein plays a key role in regulating human keratinocyte proliferation and differentiation. Although some p63-regulating microRNAs (miRNAs) have been identified in the control of epidermal homeostasis, little is known about miRNAs acting downstream of p63. In this paper, we characterized multiple p63-regulated miRNAs (miR-17, miR-20b, miR-30a, miR-106a, miR-143 and miR-455-3p) and elucidated their roles in the onset of keratinocyte differentiation.

Determination and assessment of total mercury levels in local, frozen and canned fish in Lebanon.

Fish is an important constituent of the Lebanese diet. However, very little attention in our area is given to bring awareness regarding the effect of the toxicity of mercury (Hg) mainly through fish consumption. This study aimed to report analytical data on total mercury levels in several fish species for the first time in thirty years and to also made individuals aware of the presence and danger from exposure to mercury through fish consumption.

The application of 3D micropatterning of agarose substrate for cell culture and in situ comet assays.

We report the fabrication of a 3D micropatterned agarose substrate that enables the culture of single or multiple cells. Patterning was performed on dried agarose using deep UV irradiation leading to 6-microm-deep micropatterns of 25-70 microm in diameter. Cell adhesion was facilitated by the specific grafting of ECM (extra cellular matrix) proteins such as fibronectin into the micropatterns.

Home-built integrated microarray system (IMAS). A three-laser confocal fluorescence scanner coupled with a microarray printer.

Microarray technology covers the urgent need to exploit the accumulated genetic information from large-scale sequencing projects and facilitate investigations on a genome-wide scale. Although most applications focus on DNA microarrays, the technology has expanded to microarrays of proteins, peptides, carbohydrates, and small molecules aiming either at detection/quantification of biomolecules or investigation of biomolecular interactions in a massively parallel manner. Microarray experiments require two specialized instruments: An arrayer (or printer), for construction of microarrays, and a readout instrument (scanner).

Improvement of yeast biochip sensitivity using multilayer inorganic sol-gel substrates.

Today, microarray fluorescence detection is still limited because a great proportion of hybrids remain undetectable. In this paper we describe sol-gel optical multilayers (stacks of low- and high-index layers) deposited on glass slides which increase the fluorescence of DNA microarrays and favour the detection of fluorescent targets. An alternative to the expensive and time-consuming physical vapour deposition technology is proposed.

Loss of tooth substance during root planing with various periodontal instruments: an in vitro study.

Ultrasonic and power-driven instrumentation is gaining in significance as an acceptable alternative to manual periodontal root treatment. Some question whether they do not remove too much tooth substance. Various ultrasonic scalers, hand instruments and two power-driven systems were compared by assessing the loss of tooth substance due to root instrumentation.

Multiple wavelength fluorescence enhancement on glass substrates for biochip and cell analyses.

In microarrays experiments, a serious limitation is the unreliability of low signal intensities data and the lack of reproducibility for the resulting ratios between samples and controls. Most of the light emitted by a fluorophore at the air/glass interface of a glass slide is absorbed by the glass so just a part of the emitted fluorescence is detected. To improve the sensitivity of the fluorescence detection of both common fluorophores Cy3 and Cy5 in DNA microarrays and fluorescent cell analyses, we have designed a multi layer mirror with alternative thin layers of SiO2 and HfO2.

Microfabricated systems for nucleic acid analysis.

High throughput and automation of nucleic acid analysis are required in order to exploit the information that has been accumulated from the Human Genome Project. Microfabricated analytical systems enable parallel sample processing, reduced analysis-times, low consumption of sample and reagents, portability, integration of various analytical procedures and automation. This review article discusses miniaturized analytical systems for nucleic acid amplification, separation by capillary electrophoresis, sequencing and hybridization.

Comparative clinical responses related to the use of various periodontal instrumentation.

Aim: The aim of this study was to evaluate in vivo the effectiveness of scaling and root planing of a power-driven mechanism compared with hand instruments and ultrasonic insert alone with a split-mouth design after 3 and 6 months.

Methods: Healing events after initial periodontal therapy were investigated in 20 patients with moderate-to-severe adult periodontitis. Plaque index (PlI), bleeding on probing (PBI), probing pocket depth (PPD), probing attachment level (PAL) and number of moderate and deep pockets (NMP, NDP) were recorded at baseline and 3 and 6 months after treatment.