Differential Expression of Non-Coding RNAs in Stem Cell Development and Therapeutics of Bone Disorders.

Stem cells' self-renewal and multi-lineage differentiation are regulated by a complex network consisting of signaling factors, chromatin regulators, transcription factors, and non-coding RNAs (ncRNAs). Diverse role of ncRNAs in stem cell development and maintenance of bone homeostasis have been discovered recently. The ncRNAs, such as long non-coding RNAs, micro RNAs, circular RNAs, small interfering RNA, Piwi-interacting RNAs, etc., are not translated into proteins but act as essential epigenetic regulators in stem cells' self-renewal and differentiation. Different signaling pathways are monitored efficiently by the differential expression of ncRNAs, which function as regulatory elements in determining the fate of stem cells. In addition, several species of ncRNAs could serve as potential molecular biomarkers in early diagnosis of bone diseases, including osteoporosis, osteoarthritis, and bone cancers, ultimately leading to the development of new therapeutic strategies. This review aims to explore the specific roles of ncRNAs and their effective molecular mechanisms in the growth and development of stem cells, and in the regulation of osteoblast and osteoclast activities. Furthermore, we focus on and explore the association of altered ncRNA expression with stem cells and bone turnover.

Formulation of thermoreversible gel of cranberry juice concentrate: Evaluation, biocompatibility studies and its antimicrobial activity against periodontal pathogens.

The present work aims to investigate the efficacy of thermoreversible gel of cranberry juice concentrate (CJC) as local drug delivery for the treatment of periodontitis. CJC was initially tested for its antimicrobial activities like MIC, MBC, antiadhesion, antibiofilm and time kill assay against the panel of organisms (S. mutans (SM), E. faecalis (EF), A. actinomycetemcomitans (AA), P. gingivalis (PG), T. forsythia (TF)) responsible for periapical and periodontal infections. Antimicrobial activity of CJC showed MIC value of 50mg/ml and MBC value of 100mg/ml with desirable antiadhesion (83-90%) and antibiofilm activity (70-85%). CJC was evaluated for its biocompatibility using periodontal fibroblasts by cell based MTT assay and found to be nontoxic. Influence of CJC on periodontopathogen PG derived virulence factors (fimA and kgp) was studied using real time polymerase chain reaction (RT-PCR) technique wherein down regulation of selected genes demonstrated inhibitory effect against PG virulence factors. Thermoreversible gel of CJC was formulated by cold method using poloxamer 407 as thermosensitive polymer and carbopol 934 as mucoadhesive polymer and evaluated for its gelation temperature, viscosity, gel strength and mucoadhesive strength. Comparison of optimized thermoreversible gel of CJC (500mg/ml) with commercially available chlorhexidine gluconate gel (0.2%) using agar well diffusion demonstrated equal zone of inhibition against SM, EF, AA, PG & TF. Hence the formulated thermoreversible gel of CJC could serve as a novel herbal alternative to currently available periodontal treatment modalities.

Lipid integration in neurodegeneration: an overview of Alzheimer's disease.

Various types of lipids and their metabolic products associated with the biological membrane play a crucial role in signal transduction, modulation, and activation of receptors and as precursors of bioactive lipid mediators. Dysfunction in the lipid homeostasis in the brain could be a risk factor for the many types of neurodegenerative disorders, including Alzheimer's disease, Huntington's disease, Parkinson's disease, and amyotrophic lateral sclerosis. These neurodegenerative disorders are marked by extensive neuronal apoptosis, gliosis, and alteration in the differentiation, proliferation, and development of neurons. Sphingomyelin, a constituent of plasma membrane, as well as its primary metabolite ceramide acts as a potential lipid second messenger molecule linked with the modulation of various cellular signaling pathways. Excessive production of reactive oxygen species associated with enhanced oxidative stress has been implicated with these molecules and involved in the regulation of a variety of different neurodegenerative and neuroinflammatory disorders. Studies have shown that alterations in the levels of plasma lipid/cholesterol concentration may result to neurodegenerative diseases. Alteration in the levels of inflammatory cytokines and mediators in the brain has also been found to be implicated in the pathophysiology of neurodegenerative diseases. Although several mechanisms involved in neuronal apoptosis have been described, the molecular mechanisms underlying the correlation between lipid metabolism and the neurological deficits are not clearly understood. In the present review, an attempt has been made to provide detailed information about the association of lipids in neurodegeneration especially in Alzheimer's disease.

Differential distribution and energy status-dependent regulation of the four CART neuropeptide genes in the zebrafish brain.

The cocaine- and amphetamine-regulated transcript (CART) neuropeptide has been implicated in the neural regulation of energy homeostasis across vertebrate phyla. By using gene-specific in situ hybridization, we have mapped the distribution of the four CART mRNAs in the central nervous system of the adult zebrafish. The widespread neuronal expression pattern for CART 2 and 4 suggests a prominent role for the peptide in processing sensory information from diverse modalities including olfactory and visual inputs. In contrast, CART 1 and 3 have a much more restricted distribution, predominantly located in the nucleus of the medial longitudinal fasciculus (NMLF) and entopeduncular nucleus (EN), respectively. Enrichment of CART 2 and 4 in the preoptic and tuberal areas emphasizes the importance of CART in neuroendocrine functions. Starvation resulted in a significant decrease in CART-positive cells in the nucleus recessus lateralis (NRL) and nucleus lateralis tuberis (NLT) hypothalamic regions, suggesting a function in energy homeostasis for these neurons. Similarly, the EN emerges as a novel energy status-responsive region. Not only is there abundant and overlapping expression of CART 2, 3, and 4 in the EN, but also starvation induced a decrease in CART-expressing neurons in this region. The cellular resolution mapping of CART mRNA and the response of CART-expressing nuclei to starvation underscores the importance of CART neuropeptide in energy processing. Additionally, the regional and gene-specific responses to energy levels suggest a complex, interactive network whereby the four CART gene products may have nonredundant functions in energy homeostasis.