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result(s) for
"Sleiman, Christopher"
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The Synergistic Effects of Curcumin and Chemotherapeutic Drugs in Inhibiting Metastatic, Invasive and Proliferative Pathways
by
Younes, Maria
,
Naim, Hassan Y.
,
Mardirossian, Rita
in
5-Fluorouracil
,
Alternative medicine
,
Analysis
2022
Curcumin, the main phytochemical identified from the Curcuma longa L. family, is one of the spices used in alternative medicine worldwide. It has exhibited a broad range of pharmacological activities as well as promising effects in the treatment of multiple cancer types. Moreover, it has enhanced the activity of other chemotherapeutic drugs and radiotherapy by promoting synergistic effects in the regulation of various cancerous pathways. Despite all the literature addressing the molecular mechanism of curcumin on various cancers, no review has specifically addressed the molecular mechanism underlying the effect of curcumin in combination with therapeutic drugs on cancer metastasis. The current review assesses the synergistic effects of curcumin with multiple drugs and light radiation, from a molecular perspective, in the inhibition of metastasis, invasion and proliferation. A systemic review of articles published during the past five years was performed using MEDLINE/PubMed and Scopus. The assessment of these articles evidenced that the combination therapy with various drugs, including doxorubicin, 5-fluorouracil, paclitaxel, berberine, docetaxel, metformin, gemcitabine and light radiation therapy on various types of cancer, is capable of ameliorating different metastatic pathways that are presented and evaluated. However, due to the heterogeneity of pathways and proteins in different cell lines, more research is needed to confirm the root causes of these pathways.
Journal Article
Left Ventricular Assist Device in Advanced Refractory Heart Failure: A Comprehensive Review of Patient Selection, Surgical Approaches, Complications and Future Perspectives
by
Sleiman, Christopher
,
Hamdan, Righab
,
Al Hazzouri, Antonio
in
advanced heart failure (HF)
,
biomedical advancements
,
Blood platelets
2024
The management of advanced heart failure (HF) has long posed significant challenges due to its complex and chronic nature. Heart transplantation, while effective, is not always feasible due to the limited availability of donor organs. In this context, long term mechanical circulatory support and mainly left ventricular assist devices (LVADs) have emerged as a vital intervention to fill this gap. LVAD superiority compared to medical therapy for some patients in advanced heart failure has been demonstrated either as a bridge to transplantation or as destination therapy. This literature review provides a comprehensive overview of the effectiveness, challenges, and advancements in the use of LVADs for treating advanced heart failure. It evaluates clinical outcomes associated with LVAD therapy, focusing on survival rates and quality of life improvements. The review synthesizes findings from recent studies, highlighting both the benefits and complications of LVAD implantation, such as infectious risk, thromboembolic events, hemorrhage and device malfunction. Additionally, it explores the latest technological and biomedical advancements in LVAD design, including innovations in biocompatibility, miniaturization, and power management. By examining current research, this review aims to elucidate how LVADs are transforming heart failure treatment and to offer insights into future directions for clinical practice and research.
Journal Article
Garlic and Hypertension: Efficacy, Mechanism of Action, and Clinical Implications
by
Daou, Rose-Mary
,
Romani, Maya
,
Ghadieh, Hilda E.
in
ajoene
,
allicin
,
Antihypertensive Agents - pharmacology
2024
Hypertension is a major risk factor for heart disease and stroke. Garlic has a long history of use in traditional medicine for various conditions, including hypertension. This narrative review examined the scientific evidence on the efficacy of garlic in lowering blood pressure. It explores the historical uses of garlic in different cultures for medicinal purposes and delves into the phytochemical composition of garlic, highlighting key components, like allicin and ajoene, that are believed to contribute to its potential health benefits. Clinical studies that investigated the effects of garlic and garlic-based supplements on blood pressure are presented, with the findings suggesting that garlic consumption may modestly reduce blood pressure, particularly in individuals with mild hypertension. Potential mechanisms of action include increased nitric oxide production, improved endothelial function, and antioxidant properties. While garlic may offer some benefits for blood pressure management, it should not be considered a substitute for conventional antihypertensive medications. Further large-scale, long-term clinical trials are warranted to establish the efficacy of garlic in managing hypertension, including the optimal dosage and formulation.
Journal Article
Transfer of molecular recognition information from DNA nanostructures to gold nanoparticles
by
Serpell, Christopher J.
,
Edwardson, Thomas G. W.
,
Sleiman, Hanadi F.
in
147/143
,
639/638/542/970
,
639/925/357/354
2016
DNA nanotechnology offers unparalleled precision and programmability for the bottom-up organization of materials. This approach relies on pre-assembling a DNA scaffold, typically containing hundreds of different strands, and using it to position functional components. A particularly attractive strategy is to employ DNA nanostructures not as permanent scaffolds, but as transient, reusable templates to transfer essential information to other materials. To our knowledge, this approach, akin to top-down lithography, has not been examined. Here we report a molecular printing strategy that chemically transfers a discrete pattern of DNA strands from a three-dimensional DNA structure to a gold nanoparticle. We show that the particles inherit the DNA sequence configuration encoded in the parent template with high fidelity. This provides control over the number of DNA strands and their relative placement, directionality and sequence asymmetry. Importantly, the nanoparticles produced exhibit the site-specific addressability of DNA nanostructures, and are promising components for energy, information and biomedical applications.
DNA nanostructures are typically used as molecular scaffolds. Now, it has been shown that they can also act as reusable templates for ‘molecular printing’ of DNA strands onto gold nanoparticles. The products inherit the recognition elements of the parent template: number, orientation and sequence asymmetry of DNA strands. This converts isotropic nanoparticles into complex building blocks.
Journal Article
Autism genome-wide copy number variation reveals ubiquitin and neuronal genes
by
Munson, Jeffrey
,
Zurawiecki, Danielle
,
Cai, Guiqing
in
Adhesion
,
Autism
,
Autistic Disorder - genetics
2009
Susceptibility to autism
Several lines of evidence point to genetic involvement in autism spectrum disorders (ASDs), neurodevelopmental and neuropsychiatric disorders characterized by impaired verbal communication and social interaction. The clinical and genetic complexities of the condition make it difficult to identify susceptibility factors, but two related studies now present robust evidence for a genetic involvement. The first, a genome-wide association study, identifies six single-nucleotide polymorphisms strongly associated with autism. These variants lie between two genes encoding neuronal cell-adhesion molecules (cadherins 9 and 10), suggesting possible involvement in ASD pathogenesis. The second study used copy number variation screens to identify genetic variants in two major gene pathways in children with ASDs. The changes are in the ubiquitin pathway, which has previously been associated with neurological disease, and in genes for neuronal cell-adhesion molecules.
Autism spectrum disorders (ASDs) are neurodevelopmental disorders characterized by impairments in social and communication skills. Accumulating evidence suggests a genetic component to ASDs, and here a two-stage, genome-wide approach is used to identify candidate genomic loci enriched in ASD cases. The majority of these loci are found to be involved in neuronal adhesion and ubiquitin degradation, suggesting novel susceptibility mechanisms.
Autism spectrum disorders (ASDs) are childhood neurodevelopmental disorders with complex genetic origins
1
,
2
,
3
,
4
. Previous studies focusing on candidate genes or genomic regions have identified several copy number variations (CNVs) that are associated with an increased risk of ASDs
5
,
6
,
7
,
8
,
9
. Here we present the results from a whole-genome CNV study on a cohort of 859 ASD cases and 1,409 healthy children of European ancestry who were genotyped with ∼550,000 single nucleotide polymorphism markers, in an attempt to comprehensively identify CNVs conferring susceptibility to ASDs. Positive findings were evaluated in an independent cohort of 1,336 ASD cases and 1,110 controls of European ancestry. Besides previously reported ASD candidate genes, such as
NRXN1
(ref.
10
) and
CNTN4
(refs
11
,
12
), several new susceptibility genes encoding neuronal cell-adhesion molecules, including
NLGN1
and
ASTN2
, were enriched with CNVs in ASD cases compared to controls (
P
= 9.5 × 10
-3
). Furthermore, CNVs within or surrounding genes involved in the ubiquitin pathways, including
UBE3A
,
PARK2
,
RFWD2
and
FBXO40
, were affected by CNVs not observed in controls (
P
= 3.3 × 10
-3
). We also identified duplications 55 kilobases upstream of complementary DNA
AK123120
(
P
= 3.6 × 10
-6
). Although these variants may be individually rare, they target genes involved in neuronal cell-adhesion or ubiquitin degradation, indicating that these two important gene networks expressed within the central nervous system may contribute to the genetic susceptibility of ASD.
Journal Article
Reprogramming the assembly of unmodified DNA with a small molecule
by
Serpell, Christopher J.
,
Greschner, Andrea A.
,
Petitjean, Anne
in
147/3
,
639/638/541/966
,
639/925/926/1049
2016
The ability of DNA to store and encode information arises from base pairing of the four-letter nucleobase code to form a double helix. Expanding this DNA ‘alphabet’ by synthetic incorporation of new bases can introduce new functionalities and enable the formation of novel nucleic acid structures. However, reprogramming the self-assembly of existing nucleobases presents an alternative route to expand the structural space and functionality of nucleic acids. Here we report the discovery that a small molecule, cyanuric acid, with three thymine-like faces, reprogrammes the assembly of unmodified poly(adenine) (poly(A)) into stable, long and abundant fibres with a unique internal structure. Poly(A) DNA, RNA and peptide nucleic acid (PNA) all form these assemblies. Our studies are consistent with the association of adenine and cyanuric acid units into a hexameric rosette, which brings together poly(A) triplexes with a subsequent cooperative polymerization. Fundamentally, this study shows that small hydrogen-bonding molecules can be used to induce the assembly of nucleic acids in water, which leads to new structures from inexpensive and readily available materials.
Cyanuric acid, a small molecule with three thymine-like faces, reprogrammes the assembly of unmodified poly(adenine) into long fibres with a unique internal structure. The association of adenine and cyanuric acid units into a hexameric rosette motif brings together poly(adenine) triplexes with subsequent cooperative polymerization.
Journal Article
Site-specific positioning of dendritic alkyl chains on DNA cages enables their geometry-dependent self-assembly
by
Serpell, Christopher J.
,
Edwardson, Thomas G. W.
,
Sleiman, Hanadi F.
in
639/638/541/966
,
639/925/357/341
,
639/925/926/1050
2013
Nature uses a combination of non-covalent interactions to create a hierarchy of complex systems from simple building blocks. One example is the selective association of the hydrophobic side chains that are a strong determinant of protein organization. Here, we report a parallel mode of assembly in DNA nanotechnology. Dendritic alkyl-DNA conjugates are hybridized to the edges of a DNA cube. When four amphiphiles are on one face, the hydrophobic residues of two neighbouring cubes engage in an intermolecular ‘handshake’, resulting in a dimer. When there are eight amphiphiles (four on the top and bottom cube faces, respectively), they engage in an intramolecular ‘handshake’ inside the cube. This forms the first example of a monodisperse micelle within a DNA nanostructure that encapsulates small molecules and releases them by DNA recognition. Creating a three-dimensional pattern of hydrophobic patches, like side chains in proteins, can result in specific, directed association of hydrophobic domains with orthogonal interactions to DNA base-pairing.
The site-specific incorporation of dendritic DNA amphiphiles into a DNA cage controls whether the resultant structures show intermolecular self-assembly or intramolecular assembly. Intramolecular assembly creates a hydrophobic core within the cage that is capable of encapsulating small molecules. These molecules can be released on addition of specific DNA strands.
Journal Article
Urtica dioica: Anticancer Properties and Other Systemic Health Benefits from In Vitro to Clinical Trials
2024
While conventional medicine has advanced in recent years, there are still concerns about its potential adverse reactions. The ethnopharmacological knowledge established over many centuries and the existence of a variety of metabolites have made medicinal plants, such as the stinging nettle plant, an invaluable resource for treating a wide range of health conditions, considering its minimal adverse effects on human health. The aim of this review is to highlight the therapeutic benefits and biological activities of the edible Urtica dioica (UD) plant with an emphasis on its selective chemo-preventive properties against various types of cancer, whereby we decipher the mechanism of action of UD on various cancers including prostate, breast, leukemia, and colon in addition to evaluating its antidiabetic, microbial, and inflammatory properties. We further highlight the systemic protective effects of UD on the liver, reproductive, excretory, cardiovascular, nervous, and digestive systems. We present a critical assessment of the results obtained from in vitro and in vivo studies as well as clinical trials to highlight the gaps that require further exploration for future prospective studies.
Journal Article
Rare copy number variants in over 100,000 European ancestry subjects reveal multiple disease associations
2020
Copy number variants (CNVs) are suggested to have a widespread impact on the human genome and phenotypes. To understand the role of CNVs across human diseases, we examine the CNV genomic landscape of 100,028 unrelated individuals of European ancestry, using SNP and CGH array datasets. We observe an average CNV burden of ~650 kb, identifying a total of 11,314 deletion, 5625 duplication, and 2746 homozygous deletion CNV regions (CNVRs). In all, 13.7% are unreported, 58.6% overlap with at least one gene, and 32.8% interrupt coding exons. These CNVRs are significantly more likely to overlap OMIM genes (2.94-fold), GWAS loci (1.52-fold), and non-coding RNAs (1.44-fold), compared with random distribution (
P
< 1 × 10
−3
). We uncover CNV associations with four major disease categories, including autoimmune, cardio-metabolic, oncologic, and neurological/psychiatric diseases, and identify several drug-repurposing opportunities. Our results demonstrate robust frequency definition for large-scale rare variant association studies, identify CNVs associated with major disease categories, and illustrate the pleiotropic impact of CNVs in human disease.
Associations of copy number variations (CNVs) with complex traits are challenging to study because of their low frequency. Here, the authors analyse SNP array and array comparative genomic hybridization data of 100,028 individuals and report their associations with immune-related, cardiometabolic and neuropsychiatric diseases as well as cancer.
Journal Article
Loading and selective release of cargo in DNA nanotubes with longitudinal variation
by
Karam, Pierre
,
Aldaye, Faisal A.
,
Lo, Pik Kwan
in
639/638/298/54/152
,
639/638/541
,
639/925/350/354
2010
Nanotubes hold promise for a number of biological and materials applications because of their high aspect ratio and encapsulation potential. A particularly attractive goal is to access nanotubes that exert well-defined control over their cargo, such as selective encapsulation, precise positioning of the guests along the nanotube length and triggered release of this cargo in response to specific external stimuli. Here, we report the construction of DNA nanotubes with longitudinal variation and alternating larger and smaller capsules along the tube length. Size-selective encapsulation of gold nanoparticles into the large capsules of these tubes leads to ‘nanopeapod’ particle lines with positioning of the particles 65 nm apart. These nanotubes can then be opened when specific DNA strands are added to release their particle cargo spontaneously. This approach could lead to new applications of self-assembled nanotubes, such as in the precise organization of one-dimensional nanomaterials, gene-triggered selective delivery of drugs and biological sensing.
Nanotubular structures made from different materials are being investigated for applications ranging from sensing to drug delivery, but controlling how they interact with ‘cargo’ molecules has proved challenging. Now, the selective uptake, precise positioning and triggered release of gold nanoparticles has been achieved with nanotubes assembled from triangular DNA building blocks.
Journal Article