Effects of LP533401 on vascular and bone calcification in hyperlipidemic mice.

Peripheral serotonin levels are associated with cardiovascular disease risk. We previously found that serum serotonin levels are higher in hyperlipidemic mice than wild-type mice. Evidence also suggests that serotonin regulates biomineralization, in that serotonin treatment augments TNF-a-induced matrix calcification of aortic valve interstitial cells and that a selective inhibitor of peripheral serotonin, LP533401, rescues bone loss induced by ovariectomy in mice. Thus, in the present study, we examined the effects of LP533401 on both skeletal bone mineral density (BMD) and aortic calcification in both young and older hyperlipidemic mice susceptible to calcific atherosclerosis and bone loss. By serial in vivo microCT imaging, we assessed BMD and aortic calcification of Apoe-/- mice fed an atherogenic (high cholesterol) diet alone or mixed with LP533401. Results show that in the young mice, LP533401 blunted skeletal bone loss in lumbar vertebrae but not in femurs. LP533401 also blunted the initial development of aortic calcification but not its progression. Echocardiographic analysis showed that LP533401 blunted both hyperlipidemia-induced cardiac hypertrophy and left ventricular dysfunction. In the older mice, LP533401 increased the BMD of lumbar vertebrae but not of femurs. The aortic calcification progressed in both controls and LP533401-treated mice, but, at post-treatment, LP533401-treated mice had significantly less aortic calcification than the controls. These findings suggest that LP533401 mitigates adverse effects of hyperlipidemia on skeletal and vascular tissues in site- and stage-dependent manners.

On Demand Biosensors for Early Diagnosis of Cancer and Immune Checkpoints Blockade Therapy Monitoring from Liquid Biopsy.

Recently, considerable interest has emerged in the development of biosensors to detect biomarkers and immune checkpoints to identify and measure cancer through liquid biopsies. The detection of cancer biomarkers from a small volume of blood is relatively fast compared to the gold standard of tissue biopsies. Traditional immuno-histochemistry (IHC) requires tissue samples obtained using invasive procedures and specific expertise as well as sophisticated instruments. Furthermore, the turnaround for IHC assays is usually several days. To overcome these challenges, on-demand biosensor-based assays were developed to provide more immediate prognostic information for clinicians. Novel rapid, highly precise, and sensitive approaches have been under investigation using physical and biochemical methods to sense biomarkers. Additionally, interest in understanding immune checkpoints has facilitated the rapid detection of cancer prognosis from liquid biopsies. Typically, these devices combine various classes of detectors with digital outputs for the measurement of soluble cancer or immune checkpoint (IC) markers from liquid biopsy samples. These sensor devices have two key advantages: (a) a small volume of blood drawn from the patient is sufficient for analysis, and (b) it could aid physicians in quickly selecting and deciding the appropriate therapy regime for the patients (e.g., immune checkpoint blockade (ICB) therapy). In this review, we will provide updates on potential cancer markers, various biosensors in cancer diagnosis, and the corresponding limits of detection, while focusing on biosensor development for IC marker detection.

Silver nanoparticles fabricated using medicinal plant extracts show enhanced antimicrobial and selective cytotoxic propensities.

Nanoparticles fabricated using medicinal plant extract have great potential in the area of nanomedicine. High surface-to-volume ratio of nanoparticle enhances the local active biomolecules concentration, leading to many fold increase in the medicinal potentials. The silver nanoparticles (AgNPs) fabricated using indigenous medicinal plants of India, Azadirachta indica and Syzygium cumini, have shown a significant effect on the viability of prokaryotic and eukaryotic cells. Biofabrication of AgNP was confirmed using different spectroscopic and microscopic techniques. Extraction and purification of AgNP from non-conjugated plant moieties are done using centrifugation and size exclusion chromatography. The cytotoxic propensity of AgNP formulations was screened against Gram-positive (Bacillus subtilis), Gram-negative (Escherichia coli) bacteria, cancerous (HT1080) and non-cancerous (HEK293) cell lines. The nanoparticle formulations showed a relatively higher cytotoxic propensity against Gram-positive bacteria and cancerous cell lines. In addition, the surface roughness and reactive oxygen species (ROS) measurements indicated that AgNP formulations mediate the cell activity predominantly by ROS-mediated disruptive change in membrane morphology upon direct interaction with the membrane. Hence, the nanoparticle formulations show an enhanced selective cytotoxic propensity towards Gram-positive bacteria and cancerous cell lines.