A novel lentiviral vector targets gene transfer into human hematopoietic stem cells in marrow from patients with bone marrow failure syndrome and in vivo in humanized mice

In vivo lentiviral vector (LV)-mediated gene delivery would represent a great step forward in the field of gene therapy. Therefore, we have engineered a novel LV displaying SCF and a mutant cat endogenous retroviral glycoprotein, RDTR. These RDTR/SCF-LVs outperformed RDTR-LVs for transduction of human CD34(+) cells (hCD34(+)). For in vivo gene therapy, these novel RDTR/SCF-displaying LVs can distinguish between the target hCD34(+) cells of interest and nontarget cells. Indeed, they selectively targeted transduction to 30%-40% of the hCD34(+) cells in cord blood mononuclear cells and in the unfractionated BM of healthy and Fanconi anemia donors, resulting in the correction of CD34(+) cells in the patients. Moreover, RDTR/SCF-LVs targeted transduction to CD34(+) cells with 95-fold selectivity compared with T cells in total cord blood. Remarkably, in vivo injection of the RDTR/SCF-LVs into the BM cavity of humanized mice resulted in the highly selective transduction of candidate hCD34(+)Lin(-) HSCs. In conclusion, this new LV will facilitate HSC-based gene therapy by directly targeting these primitive cells in BM aspirates or total cord blood. Most importantly, in the future, RDTR/SCF-LVs might completely obviate ex vivo handling and simplify gene therapy for many hematopoietic defects because of their applicability to direct in vivo inoculation.     

Endocrine disrupting chemical Bisphenol A and its potential effects on female health

Background and aimA large number of chemical compounds with endocrine-disrupting activity have been documented. These chemicals are ubiquitous and widely used in many products of our daily lives. Bisphenol A (BPA) is among the most common Endocrine Disrupting Chemical (EDC) that has been used for many years in the manufacture of polycarbonate plastics and epoxy resins. There is growing evidence that exposure to these EDCs poses a possible health risk. This review focuses on the effect of EDCs, in particular, BPA on female reproduction and Polycystic Ovary Syndrome (PCOS), which is the most prevalent endocrine disorder of reproductively aged women.MethodsA relevant literature survey was conducted with Google scholar and Pubmed using several appropriate keywords to select the most relevant studies evaluating the role of endocrine disrupting-chemicals in female reproduction.ResultsThe female menstrual cycle and fertility are very sensitive to hormonal imbalance and alteration in endocrine function during critical times and different stages of lifecycle owing to EDC exposure results in many abnormalities like menstrual irregularities, impaired fertility, PCOS, and Endometriosis among others. BPA is the most extensively studied EDC worldwide and has been strongly associated with female reproductive health.ConclusionEDCs lead to deleterious effects on human health including reproductive health which are of global concern. Exposure to EDCs in early life can elicit disease in adult life and maybe even transgenerational. There is an immediate need to minimize the ill effect of EDCs which can be tackled through the collection of more data to clarify the clinical implications of EDCs.     

MSX2 Gene Duplication in a Patient with Eye Development Defects

Background: MSX2 mutations are a very rare cause of craniosynostosis. Gain-of-function mutations may lead to the Boston-type craniosynostosis with limb defects and refraction errors, whereas loss-of-function mutations causes primary osseous defects such as enlarged parietal foramina.

Materials and Methods: Herein we report the case of a child with bicoronal synostosis and cutaneous syndactylies, who presented iridal and chorioretinal colobomas. Due to the craniofacial features that were prominent in the clinical picture, the genes involved in craniosynostosis were explored.

Results: The patient disclosed an intragenic duplication of the entire MSX2 gene whereas no mutation was identified in any major genes known to be involved in craniosynostosis.

Conclusion: This is the first report of an eye development defect due to an increase in the MSX2 copy number in a human being. The implication of this gene in eye development has already been shown in several animal models. Indeed, overexpression of the Msx2 gene in a mouse model resulted also in optic nerve aplasia and microphthalmia. This report expands the phenotypic spectrum of the MSX2 mutations impacting early ocular development knowledge.     

Chemical constituents from the stems of<Emphasis Type="Italic">Morinda citrifolia</Emphasis> linn

Studies on the chemical constituents of the stems of Morinda citrifolia, Linn. have led to the isolation of two new compounds, morindicone (9-hydroxy-2-methoxy-4-methyl-3,10-anthracenedione, 1) and morinthone (4-methoxy-3-heptadecylxanthone, 2), as well as two known constituents, 1-hydroxy-2-methylanthraquinone (3) and 2-hydroxymethylanthraquinone (4). Their structures were elucidated by spectral analysis including 2D NMR techniques.     

Endocarditis due to Kytococcus schroeteri: case report and review of the literature

We report the third case of endocarditis caused by the newly described micrococcal species Kytococcus schroeteri. A 49-year-old woman was admitted to the hospital with suspected prosthetic valve endocarditis. Five blood cultures and prosthetic valve cultures grew the same type of organism, initially identified as Micrococcus sp. Assignment to the genus Kytococcus was suggested by the arginine dihydrolase activity and resistance to oxacillin. After sequencing of the 16S rRNA genes, the isolate was recognized as K. schroeteri. The patient was treated first with vancomycin combined with gentamicin and later with pristinamycin and rifampin. Three cases of K. schroeteri endocarditis described within a short period of time might indicate a specific pathogenicity of this new species. The isolation of kytococci from normally sterile sites should not be overlooked.