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1.
Am J Transl Res ; 13(10): 11353-11363, 2021.
Article in English | MEDLINE | ID: mdl-34786063

ABSTRACT

Colon adenocarcinoma (COAD) is a common tumor of the gastrointestinal tract with a high mortality rate. Current research has identified many genes associated with immune infiltration that play a vital role in the development of COAD. In this study, we analysed the prognostic and diagnostic features of such immune-related genes in the context of colonic adenocarcinoma (COAD). We analysed 17 overlapping gene expression profiles of COAD and healthy samples obtained from TCGA-COAD and public single-cell sequencing resources, to identify potential therapeutic COAD targets. We evaluated the abundance of immune infiltration with those genes using the TIMER (Tumor Immune Estimation Resource) deconvolution method. Subsequently, we developed predictive and survival models to assess the prognostic value of these genes. The LGALS4 (Galectin-4) gene was found to be significantly (P<0.05) downregulated in COAD and bladder urothelial carcinoma (BLCA) compared to healthy samples. We identified LGALS4 as a prognostic and diagnostic marker for multiple cancer types, including COAD and BLCA. Our analysis reveals a series of novel candidate drug targets, as well as candidate molecular markers, that may explain the pathogenesis of COAD and BLCA. LGALS4 gene is associated with multiple cancer types and is a possible prognostic, as well as diagnostic, marker of COAD and BLCA.

2.
ACS Appl Mater Interfaces ; 13(2): 2382-2398, 2021 Jan 20.
Article in English | MEDLINE | ID: mdl-33406837

ABSTRACT

In this article, we describe a method of delivery of chondroitin sulfate to skin as nanoparticles and demonstrate its anti-inflammatory and antioxidant role using UV irradiation as a model condition. These nanoparticles, formed through electrostatic interactions of chondroitin sulfate with a skin-penetrating peptide, were found to be homogenous with positive surface charges and stable at physiological and acidic pH under certain conditions. They were able to enter into the human keratinocyte cell line (HaCaT), artificial skin membrane (mimicking the human skin), and mouse skin tissue unlike free chondroitin sulfate. The preapplication of nanoparticles also exhibited reduced levels of oxidative stress, cyclobutane pyrimidine dimer formation, TNF-α, and so on in UV-B-irradiated HaCaT cells. In an acute UV-B irradiation mouse model, their topical application resulted in reduced epidermal thickness and sunburn cells, unlike in the case of free chondroitin sulfate. Thus, a completely noninvasive method was used to deliver a bio-macromolecule into the skin without using injections or abrasive procedures.


Subject(s)
Anti-Inflammatory Agents/administration & dosage , Antioxidants/administration & dosage , Chondroitin Sulfates/administration & dosage , Drug Carriers/chemistry , Peptides/chemistry , Sunburn/prevention & control , Administration, Topical , Animals , Anti-Inflammatory Agents/pharmacokinetics , Anti-Inflammatory Agents/therapeutic use , Antioxidants/pharmacokinetics , Antioxidants/therapeutic use , Cell Line , Chondroitin Sulfates/pharmacokinetics , Chondroitin Sulfates/therapeutic use , Drug Carriers/metabolism , Female , Humans , Keratinocytes/drug effects , Keratinocytes/metabolism , Keratinocytes/pathology , Mice , Mice, Inbred BALB C , Nanoparticles/chemistry , Nanoparticles/metabolism , Oxidative Stress/drug effects , Peptides/metabolism , Skin Absorption , Sunburn/metabolism , Sunburn/pathology , Ultraviolet Rays/adverse effects
3.
Am J Transl Res ; 13(12): 13697-13709, 2021.
Article in English | MEDLINE | ID: mdl-35035708

ABSTRACT

Atopic dermatitis (AD), or atopic eczema, is one of the most common inflammatory skin diseases with up to 10% prevalence in adults, and approximately 15-20% in children in industrialized countries. As a result, there is an unmet need for faster, safer, and effective treatments for AD. AD pathogenesis represents a complex interplay between multiple factors, such as environmental factors or stimuli, genetic factors, immune dysfunctions. However, although multi-omics label studies have been very useful in understanding the pathophysiological mechanisms of AD and its clinical manifestations, there have been very few studies that integrate different labels of omics data. Here, we attempted to integrate gene expression and metabolomics datasets from multiple different publicly available AD cohort datasets and conduct an integrated systems-level AD analysis. We used four different GEO transcriptome data sets and, by applying an elastic net machine learning algorithm, identified robust hub genes that can be used as signatures, for example, H2AFX, MCM7, ESR1 and SF3A2. Moreover, we investigated potential associations of those genes by applying a pathway-based approach over metabolomics and miRNA datasets. Our results revealed potential novel associations between fatty acids and peroxisomal lipid metabolism pathways, as well as with several microRNAs.

4.
Nanomedicine ; 12(5): 1193-204, 2016 07.
Article in English | MEDLINE | ID: mdl-26772428

ABSTRACT

UNLABELLED: Increasing amounts of metal-based implants are used for orthopedic or dental surgeries throughout the world. Still several implant-related problems such as inflammation, loosening and bacterial infection are prevalent. These problems stem from the immediate microbial contamination and failure of initial osteoblast adhesion. Additionally, bacterial infections can cause serious and life-threatening conditions such as osteomyelitis. Here, antibiotic (gentamicin)-loaded silk protein fibroin (non-mulberry silkworm, Antheraea mylitta) nanoparticles are fabricated and deposited over the titanium surface to achieve sustained drug release in vitro and to alter the surface nano-roughness. Based on the altered surface topography, chemistry and antibacterial activity, we conclude that the nanoparticle-deposited surfaces are superior for osteoblast adhesion, proliferation and differentiation in comparison to bare Ti. This method can be utilized as a cost-effective approach in implant modification. FROM THE CLINICAL EDITOR: Titanium-based implants are commonly used in the field of orthopedics or dentistry. Surface modification of an implant is vital to ensure osseointegration. In this article, the author investigated the use of silk protein fibroins for metal surface modification and also for drug delivery against bacteria. The encouraging data should provide a new method in terms of nanotechnology in the respective clinical fields.


Subject(s)
Fibroins , Nanoparticles , Osteogenesis , Titanium , Anti-Bacterial Agents , Drug Delivery Systems , Humans , Surface Properties
5.
Biopolymers ; 97(6): 455-67, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22241173

ABSTRACT

The silk produced by silkworms are biopolymers and can be classified into two types--mulberry and nonmulberry. Mulberry silk of silkworm Bombyx mori has been extensively explored and used for century old textiles and sutures. But for the last few decades it is being extensively exploited for biomedical applications. However, the transformation of nonmulberry silk from being a textile commodity to biomaterials is relatively new. Within a very short period of time, the combination of load bearing capability and tensile strength of nonmulberry silk has been equally envisioned for bone, cartilage, adipose, and other tissue regeneration. Adding to its advantage is its diverse morphology, including macro to nano architectures with controllable degradation and biocompatibility yields novel natural material systems in vitro. Its follow on applications involve sustained release of model compounds and anticancer drugs. Its 3D cancer models provide compatible microenvironment systems for better understanding of the cancer progression mechanism and screening of anticancer compounds. Diversely designed nonmulberry matrices thus provide an array of new cutting age technologies, which is unattainable with the current synthetic materials that lack biodegradability and biocompatibility. Scientific exploration of nonmulberry silk in tissue engineering, regenerative medicine, and biotechnological applications promises advancement of sericulture industries in India and China, largest nonmulberry silk producers of the world. This review discusses the prospective biomedical applications of nonmulberry silk proteins as natural biomaterials.


Subject(s)
Biocompatible Materials/chemistry , Bombyx/physiology , Fibroins/chemistry , Larva/physiology , Pupa/physiology , Animals , Biomimetic Materials/chemistry , Bombyx/classification , Delayed-Action Preparations/chemistry , Drug Carriers/chemistry , Fibroins/ultrastructure , Humans , Morus/parasitology , Tensile Strength , Tissue Engineering , Tissue Scaffolds
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