CaCO3 Nanoparticles Delivering MicroRNA-200c Suppress Oral Squamous Cell Carcinoma.

MicroRNA (miR)-200c suppresses the initiation and progression of oral squamous cell carcinoma (OSCC), the most prevalent head and neck cancer with high recurrence, metastasis, and mortality rates. However, miR-200c-based gene therapy to inhibit OSCC growth has yet to be reported. To develop an miR-based gene therapy to improve the outcomes of OSCC treatment, this study investigates the feasibility of plasmid DNA (pDNA) encoding miR-200c delivered via nonviral CaCO3-based nanoparticles to inhibit OSCC tumor growth. CaCO3-based nanoparticles with various ratios of CaCO3 and protamine sulfate (PS) were used to transfect pDNA encoding miR-200c into OSCC cells, and the efficiency of these nanoparticles was evaluated. The proliferation, migration, and associated oncogene production, as well as in vivo tumor growth for OSCC cells overexpressing miR-200c, were also quantified. It was observed that, while CaCO3-based nanoparticles improve transfection efficiencies of pDNA miR-200c, the ratio of CaCO3 to PS significantly influences the transfection efficiency. Overexpression of miR-200c significantly reduced proliferation, migration, and oncogene expression of OSCC cells, as well as the tumor size of cell line-derived xenografts (CDX) in mice. In addition, a local administration of pDNA miR-200c using CaCO3 delivery significantly enhanced miR-200c transfection and suppressed tumor growth of CDX in mice. These results strongly indicate that the nanocomplexes of CaCO3/pDNA miR-200c may potentially be used to reduce oral cancer recurrence and improve clinical outcomes in OSCC treatment, while more comprehensive examinations to confirm the safety and efficacy of the CaCO3/pDNA miR-200c system using various preclinical models are needed.

MEMO1 Is Required for Ameloblast Maturation and Functional Enamel Formation.

Coordinated mineralization of soft tissue is central to organismal form and function, while dysregulated mineralization underlies several human pathologies. Oral epithelial-derived ameloblasts are polarized, secretory cells responsible for generating enamel, the most mineralized substance in the human body. Defects in ameloblast development result in enamel anomalies, including amelogenesis imperfecta. Identifying proteins critical in ameloblast development can provide insight into specific pathologies associated with enamel-related disorders or, more broadly, mechanisms of mineralization. Previous studies identified a role for MEMO1 in bone mineralization; however, whether MEMO1 functions in the generation of additional mineralized structures remains unknown. Here, we identify a critical role for MEMO1 in enamel mineralization. First, we show that Memo1 is expressed in ameloblasts and, second, that its conditional deletion from ameloblasts results in enamel defects, characterized by a decline in mineral density and tooth integrity. Histology revealed that the mineralization defects in Memo1 mutant ameloblasts correlated with a disruption in ameloblast morphology. Finally, molecular profiling of ameloblasts and their progenitors in Memo1 oral epithelial mutants revealed a disruption to cytoskeletal-associated genes and a reduction in late-stage ameloblast markers, relative to controls. Collectively, our findings integrate MEMO1 into an emerging network of molecules important for ameloblast development and provide a system to further interrogate the relationship of cytoskeletal and amelogenesis-related defects.

Childhood asthma education project - abstract

An educational programme, consisting of a booklet explained by a nurse in four sessions and the showing of a videotaped dramatization of the same informaton, was administered to 16 parents of asthmatic children. Fifteen comparable parents were followed and used as a control group. This preliminary report shows that the parents of both groups had similar levels of knowledge of asthma at the initial test. On retesting at the six-month follow-up, the parents in both groups did significantly better than on the initial test. However, the experimental group's improvement was statistically better than that of the controls (p=0.003). More important are the changes in attitude and behaviour implied by the higher rate of casualty visits, and the higher rate of attacks identified in cases as compared with controls. The fall in admissions among cases, while controls had a steady rate of admissions in both the year of the study and in the preceeding year, has positive economic implications that are especially exciting in a developing country such as ours (AU)

Neonatal jaundice at Port-of-Spain General Hospital - abstract

Neonatal jaundice is a major cause of morbidity in developing countries. The preventions of kernicterus is one of the goals of paediatricians in these countries. In an attempt to elucidate the aetiology of neonatal jaundice in our population, a prospective study was done at the Port-of Spain General Hospital from 15th June, 1986 to 30th September, 1986. Ninety-five patients were enrolled; 63 percent of the sample were of African descent, 19 percent of East Indian descent and 11 percent of mixed race. Forty-four per cent had ABO incompatibility, and 44 percent had no blood incompatibility, of which 26 percent were glucose-6-phosphate dehydrogenase (G6PD) deficient. G6PD deficiency was found in 21 percent of the total sample. In 33 percent of the sample, the aetiology is unknown. Moderate/severe jaundice (bilirubin > 16 mg/100 ml) was seen in 58 percent of the ABO incompatible group, 55 percent of the "unknown" group, 43 percent of the Rh incompatible group and 75 percent of the G6PD-deficient group. Most of the ABO incompatibility and Rh incompatibility cases (92 percent and 85 percent) developed jaundice within 48 hours of birth. In contrast, only 55 percent of the G6PD-deficient group and 50 percent of the "unknown' group developed jaundice early. Camphor was used by 60 percent of the G6PD-deficient group, 35 percent of the ABO incompatible group and 39 percent of the "unknown" group. Since 1984, there has been an active policy at the Port-of-Spain General Hospital which ensures that all children with ABO incompatibility are observed for forty-eight hours for the development of jaundice. It is recommended that a screening policy for G6PD deficiency should be adopted, since it is an important cause of jaundice in the children, presents later and can cause moderate/severe jaundice. Camphor use should be discouraged since it is a known precipitant of haemolysis in G6PD-deficient individuals (AU)

Visceral larva migrans: a family study - abstract

Visceral Larva Migrans (VLM) is difficult to diagnose on clinical grounds. There has not been adequate laboratory backup in making the diagnosis. Hence little is known of the prevalence of VLM in Trinidad. We have used a recently described ELISA test to identify a family at high risk for VLM based on the following criteria: history of pica, recurrent wheezing in the absence of a family history of bronchial asthma and extreme eosinophilia (over 30 percent peripheral eosinophils). In this paper, we describe the index case in detail and investigate the other members of the family, all of whom proved positive for VLM by serological testing. This is a probably an important public health problem (AU)