Stem cell treatment of degenerative eye disease

Stem cell therapies are being explored extensively as treatments for degenerative eye disease, either for replacing lost neurons, restoring neural circuits or, based on more recent evidence, as paracrine-mediated therapies in which stem cell-derived trophic factors protect compromised endogenous retinal neurons from death and induce the growth of new connections. Retinal progenitor phenotypes induced from embryonic stem cells/induced pluripotent stem cells (ESCs/iPSCs) and endogenous retinal stem cells may replace lost photoreceptors and retinal pigment epithelial (RPE) cells and restore vision in the diseased eye, whereas treatment of injured retinal ganglion cells (RGCs) has so far been reliant on mesenchymal stem cells (MSC). Here, we review the properties of non-retinal-derived adult stem cells, in particular neural stem cells (NSCs), MSC derived from bone marrow (BMSC), adipose tissues (ADSC) and dental pulp (DPSC), together with ESC/iPSC and discuss and compare their potential advantages as therapies designed to provide trophic support, repair and replacement of retinal neurons, RPE and glia in degenerative retinal diseases. We conclude that ESCs/iPSCs have the potential to replace lost retinal cells, whereas MSC may be a useful source of paracrine factors that protect RGC and stimulate regeneration of their axons in the optic nerve in degenerate eye disease. NSC may have potential as both a source of replacement cells and also as mediators of paracrine treatment

Pharmacogenomics of osteonecrosis of the jaw

Osteonecrosis of the jaw (ONJ) is a rare but serious drug induced adverse event, mainly associated with the use of antiresorptive medications, such as intravenous (IV) bisphosphonates (BPs) in cancer patients. In this review, we evaluated all the pharmacogenomic association studies for ONJ published up to December 2018. To date, two SNPs (CYP2C8 rs1934951 and RBMS3 rs17024608) were identified to be associated with ONJ by two genome-wide association studies (GWAS). However, all six subsequent candidate gene studies failed to replicate these results. In addition, six discovery candidate gene studies tried to identify the genetic markers in several genes associated with bone remodeling, bone mineral density, or osteoporosis. After evaluating the results of these 6 studies, none of the SNPs was significantly associated with ONJ. Recently, two whole-exome sequencing (WES) analysis (including one from our group) were performed to identify variants associated with ONJ. So far, only our study successfully replicated discovery result indicating SIRT1 SNP rs7896005 to be associated with ONJ. However, this SNP also did not reach genome-wide significance. The major limitations of these studies include lack of replication phases and limited sample sizes. Even though some studies had larger sample sizes, they recruited healthy individuals as controls, not subjects treated with BPs. We conclude that a GWAS with a larger sample size followed by replication phase will be needed to fully investigate the pharmacogenomic markers of ONJ

Photobiomodulation for Lowering Pain after Tonsillectomy: Low Efficacy and a Possible Unexpected Adverse Effect

Background: Tonsillectomy is one of the most common surgical procedures performed in children as a treatment for obstructive sleep apnea due to tonsil hypertrophy or highly recurrent tonsillitis. Odynophagia, associated with food refusal for the first few days, is a common post-operative complaint. Available drugs for pain management, while efficacious, present some drawbacks, and a novel strategy would be welcome. Photobiomodulation (PBMT), in this context, can represent a possible choice, together with pharmacological therapy. The aim of this study was to evaluate PBMT effects compared to standard pain therapy on nociceptive sensation at different time points and administration of painkiller. Methods: A registered, controlled, randomized, double-blind clinical trial was performed. Twenty-two patients were recruited and divided into laser-treated (T) or untreated (UT) groups, based on random assignment. In T group, immediately after tonsillectomy, performed with cold dissection technique, laser light was applied to the surgery site (using a Cube 4 from Eltech K-Laser s.r.l., Treviso, Italy), and then hemostasis was performed using bismuth subgallate paste. In C group, the same procedure was performed, except that laser light was switched off. The primary outcome was the difference in pain scores between subject receiving photobiomodulation (PBMT) and subjects receiving standard care after 24 h; the secondary outcomes were pain scores at awakening and at 48 h together with distress (delirium) at awakening. Results: Two patients from the T group experienced a post-surgery bleeding, and one of them required revision of the hemostasis under general anesthesia. A preliminary analysis of pain sensation reported by the patients or caregivers did not show differences between treated and untreated subjects. Conclusion: These data suggest that PBMT could increase post-surgical bleeding

Polymorphisms in regulators of xenobiotic transport and metabolism genes PXR and CAR do not affect multiple myeloma risk : a case-control study in the context of IMMEnSE consortium

The exposure to pesticides and toxic compounds in xenobiotic transport and metabolism genes has been shown to affect risk of developing multiple myeloma (MM). Therefore, we hypothesized that genetic variations in xenobiotic transport and metabolism regulator genes PXR (NR1I2) and CAR (NR1I3) could determine a difference in MM susceptibility. Ten tagging single-nucleotide polymorphisms (SNPs) for PXR and seven for the CAR genes were selected and genotyped in 627 MM cases and 883 controls collected in the context of the International Multiple Myeloma rESEarch (IMMEnSE) consortium. None of the 17 SNPs investigated showed significant association with MM risk either alone or when combined in haplotypes. Significant SNP-SNP interactions were not found, neither with 58 previously genotyped polymorphisms in ABC transporters. We can therefore exclude that common genetic variants in the xenobiotic transport and metabolism regulator genes PXR and CAR affect MM risk