Role of Laser Biostimulation in Treatment of Oral Submucous Fibrosis: A Clinical Trial

AIM: To evaluate the efficacy of Low Level Laser Therapy (LLLT) in treatment of Oral Submucous Fibrosis (OSMF).MATERIAL & METHODS: 20 patients with a clinical diagnosis of OSMF were included in the study after informed consents and measurements of mouth opening (mm) and burning sensation (VAS) were made at day 0. Laser biostimulation was performed on right and left cheeks in anterior and posterior bands for 3 cycles of 10 seconds each. They were recalled for follow-up measurements and Laser biostimulation at 3rd, 7th and 15th day. The paired t-test was applied for analysing significant differences, if any, using SPSS version 21.0.RESULTS: In the follow up recordings, generally, there was an increase in mouth opening after LLLT therapy and a significant difference was seen in males(p=.04) as well as the total population(p=0.02). Burning sensation(VAS Scale), on day zero was 5.5±1.20, which was reduced to 3.4±.084 on the 15th day with a significant difference seen in the entire study population(p=0.03).CONCLUSION: Biostimulation by Laser in the treatment of OSMF is a good non-invasive, painless and quick alternative treatment modality for the management of diseases

SRF transcriptionally regulates the oligodendrocyte cytoskeleton during CNS myelination.

Myelination of neuronal axons is essential for nervous system development. Myelination requires dramatic cytoskeletal dynamics in oligodendrocytes, but how actin is regulated during myelination is poorly understood. We recently identified serum response factor (SRF)-a transcription factor known to regulate expression of actin and actin regulators in other cell types-as a critical driver of myelination in the aged brain. Yet, a major gap remains in understanding the mechanistic role of SRF in oligodendrocyte lineage cells. Here, we show that SRF is required cell autonomously in oligodendrocytes for myelination during development. Combining ChIP-seq with RNA-seq identifies SRF-target genes in oligodendrocyte precursor cells and oligodendrocytes that include actin and other key cytoskeletal genes. Accordingly, SRF knockout oligodendrocytes exhibit dramatically reduced actin filament levels early in differentiation, consistent with its role in actin-dependent myelin sheath initiation. Surprisingly, oligodendrocyte-restricted loss of SRF results in upregulation of gene signatures associated with aging and neurodegenerative diseases. Together, our findings identify SRF as a transcriptional regulator that controls the expression of cytoskeletal genes required in oligodendrocytes for myelination. This study identifies an essential pathway regulating oligodendrocyte biology with high relevance to brain development, aging, and disease

Young CSF restores oligodendrogenesis and memory in aged mice via Fgf17

Recent understanding of how the systemic environment shapes the brain throughout life has led to numerous intervention strategies to slow brain ageing1-3. Cerebrospinal fluid (CSF) makes up the immediate environment of brain cells, providing them with nourishing compounds4,5. We discovered that infusing young CSF directly into aged brains improves memory function. Unbiased transcriptome analysis of the hippocampus identified oligodendrocytes to be most responsive to this rejuvenated CSF environment. We further showed that young CSF boosts oligodendrocyte progenitor cell (OPC) proliferation and differentiation in the aged hippocampus and in primary OPC cultures. Using SLAMseq to metabolically label nascent mRNA, we identified serum response factor (SRF), a transcription factor that drives actin cytoskeleton rearrangement, as a mediator of OPC proliferation following exposure to young CSF. With age, SRF expression decreases in hippocampal OPCs, and the pathway is induced by acute injection with young CSF. We screened for potential SRF activators in CSF and found that fibroblast growth factor 17 (Fgf17) infusion is sufficient to induce OPC proliferation and long-term memory consolidation in aged mice while Fgf17 blockade impairs cognition in young mice. These findings demonstrate the rejuvenating power of young CSF and identify Fgf17 as a key target to restore oligodendrocyte function in the ageing brain

The role of sterol 12α- hydroxylase (Cyp8b1) in glucose homeostasis

Besides their role in facilitating lipid absorption, bile acids are increasingly being recognized as signaling molecules that activate cell-signaling receptors. Targeted disruption of cytochrome P450 sterol 12α- hydroxylase (Cyp8b1) results in complete absence of cholic acid and its derivatives. The impact of Cyp8b1 deletion has predominantly been studied with respect to development of atherosclerosis and lipid and bile acid metabolism. Here, for the first time, we investigate the impact of Cyp8b1 deletion on glucose homeostasis. Absence of Cyp8b1 results in improved glucose tolerance, enhanced insulin sensitivity and improved β-cell function in Cyp8b1-/- mice. In addition, our results show that reduced intestinal fat absorption in the absence of biliary cholic acid in Cyp8b1-/- mice leads to increase in free fatty acids reaching the ileal L-cells. This increase in the luminal free fatty acids correlated with significantly increased secretion of the incretin hormone, glucagon like peptide-1 (GLP-1). GLP-1 in turn increases the biosynthesis and secretion of insulin from β-cells, leading to the improved glucose tolerance observed in the Cyp8b1-/- mice. Treatment of Cyp8b1-/- mice with Exendin (9-39) amide, a potent and selective GLP-1 receptor antagonist, restored their glucose tolerance to control levels. Furthermore, cholic acid feeding in Cyp8b1-/- mice resulted in complete normalization of not only fat and glucose tolerance, but also GLP-1 secretion. These data suggest that the absence of cholic acid leads to the improvement in the glycemic control of Cyp8b1-/- mice. Thus, our data demonstrates the importance of Cyp8b1 inhibition in the regulation of glucose metabolism.Medicine, Faculty ofMedical Genetics, Department ofGraduat

Loss of Cyp8b1 Improves Glucose Homeostasis by Increasing GLP-1

Besides their role in facilitating lipid absorption, bile acids are increasingly being recognized as signaling molecules that activate cell-signaling receptors. Targeted disruption of the sterol 12-hydroxylase gene (Cyp8b1) results in complete absence of cholic acid (CA) and its derivatives. Here we investigate the effect of Cyp8b1 deletion on glucose homeostasis. Absence of Cyp8b1 results in improved glucose tolerance, insulin sensitivity, and -cell function, mediated by absence of CA in Cyp8b1(-/-) mice. In addition, we show that reduced intestinal fat absorption in the absence of biliary CA leads to increased free fatty acids reaching the ileal L cells. This correlates with increased secretion of the incretin hormone GLP-1. GLP-1, in turn, increases the biosynthesis and secretion of insulin from -cells, leading to the improved glucose tolerance observed in the Cyp8b1(-/-) mice. Thus, our data elucidate the importance of Cyp8b1 inhibition on the regulation of glucose metabolism

Direct intracerebral delivery of a miR-33 antisense oligonucelotide into mouse brain increases brain ABCA1 expression

status: publishe

Disparities in Outcomes of Hospitalizations Due to Multiple Myeloma: A Nationwide Comparison.

Background With the advent of novel treatments, there is a declining trend in the multiple myeloma (MM) mortality rate with an increasing hospitalization rate. However, there is limited population-based data on trends and outcomes of hospitalizations due to MM in the United States (US). Methods We analyzed the publicly available Nationwide Inpatient Sample (NIS) from 2007 to 2017 to identify MM hospitalizations. Results Hospitalizations for MM increased from 17,100 (8.71%) in 2007 to 19,490 (9.92%) in 2017. The in-hospital mortality rate declined from 8.4% in 2007 to 4.9% in 2017 (