miR-620 promotes tumor radioresistance by targeting 15-hydroxyprostaglandin dehydrogenase (HPGD)

MicroRNA contribute to tumor radiation resistance, which is an important clinical problem, and thus we are interested in identifying and characterizing their function. We demonstrate that miR-620 contributes to radiation resistance in cancer cells by increasing proliferation, and decreasing the G2/M block. We identify the hydroxyprostaglandin dehydrogenase 15-(nicotinamide adenine dinucleotide) (HPGD/15-PGDH) tumor suppressor gene as a direct miR-620 target, which results in increased prostaglandin E2 (PGE2) levels. Furthermore, we show that siRNA targeting of HPGD or administration of exogenous PGE2 recapitulates radioresistance. Targeting of the EP2 receptor that responds to PGE2 using pharmacological or genetic approaches, abrogates radioresistance. Tumor xenograft experiments confirm that miR-620 increases proliferation and tumor radioresistance in vivo. Regulation of PGE2 levels via targeting of HPGD by miR-620 is an innovative manner by which a microRNA can induce radiation resistance.     

Protective effects of Hibiscus tiliaceus L. methanolic extract to V79 cells against cytotoxicity and genotoxicity induced by hydrogen peroxide and tert-butyl-hydroperoxide

Plants of the genus Hibiscus thrives produce a diversity of molecules with bioactive properties. In a previous study of Hibiscus tiliaceus L. methanolic extract (HME) using bacteria and yeast, as test media, it has been shown that HME strongly inhibited the mutagenic action of H₂O₂ or tert-butyl-hydroperoxide (t-BHP). Here, our interest is to evaluate the genotoxicity and the antigenotoxic/antimutagenic properties of HME using oxidative challenge with H₂O₂ and t-BHP in V79 cells. We determined cytotoxicity using clonal survival assay; evaluated DNA damage using the comet assay and the micronucleus test in binucleated cells besides of the lipid peroxidation degree and the reduced glutathione content. We examined the ability of HME in quenching hydroxyl radical by means of a HPLC-based method utilizing the hypoxanthine/xanthine oxidase assay. At concentrations ranging from 0.001 to 0.1 mg/mL, HME was not cytotoxic, genotoxic or mutagenic. Treatment with non-cytotoxic concentrations of HME increased cell survival after H₂O₂ and t-BHP exposure and prevented DNA damage. The pre-treatment with HME also was able to decrease the mutagenic effect of these genotoxins, evaluated using the micronucleus test. HME prevented the increase in lipid peroxidation and decrease in GSH content in response to the oxidative challenge. Therefore, the ability in preventing against H₂O₂- and t-BHP-induced GSH depletion and lipid peroxidation was probably a major contribution to the cytoprotective effects. Moreover, HME acts as a hydroxyl radical scavenger. In summary, HME did not have a harmful or inhibitory effect on the growth of V79 cells and presented antioxidant activity, consequently, both antigenotoxic and antimutagenic effects against oxidative DNA damage.     

Comparison between research data and routinely collected register data for studying childhood health

Cohort studies are usually based on detailed information gathered on a limited number of individuals. Increasing collection of administrative registers offers an alternative method to gather health data. In the first study health information from birth until the age of seven years on 8708 children born in the two most northern provinces of Finland in 1985–86 was gathered through questionnaires, medical record reviews, medical examinations and some register data. In the second study, similar information on 8222 children born in the same provinces in 1987 was gathered using administrative registers. Both data collection methods gave equal results for mortality, long-term medication, and cumulative incidence of diabetes and intellectual disabilities. The register data identified more children with delayed development, but less children with long-term illness (77% of the level identified by the research data), with asthma (74%), and with epilepsy (40%). The register data was unsuitable for investigating hearing and vision disorders. The administrative data gave a gender ratio similar to that of the research data for two of the variables with poor coverage (asthma and epilepsy), but identified more boys with long-term illness in general than the research data. Administrative registers are useful for studying many long-term health problems, e.g. those resulting in hospital care or social benefits or those registered in vital statistics. Specific cohort studies with separate data collection is still needed to study for example outpatient care, self-assessed health, growth and development.     

Anosmia in association with occupational use of a waterproof coating chemical

A case of acute permanent anosmia is described in a renovation worker during exposure to a waterproof coating chemical. The chemical consisted of several substances of which four (acetone, acrylates, butyl acetate and carbon disulfide) has been previously reported to induce hyposmia or anosmia in workers. Other aetiologies were clinically excluded but a large arachnoidea cyst in the frontal part of the left temporobasal fossa with possible compression of the left entorhinal cortex. The toxic aetiology of anosmia is supported by the acute onset and the temporal relationship with occupational exposure. The silent cyst as the cause of anosmia is improbable, but it may have had some contributory role. Our case illustrates both the challenges when clinically examining patients with work-related olfactory impairment and the importance of multi-disciplinary approach to such patients.     

Association between school performance, breast milk intake and fatty acid profile of serum lipids in ten-year-old cleft children

The fatty acid profiles of serum lipids were examined in 53 ten-year-old cleft children. The children presented with different cleft types (cleft lip, cleft lip and palate, isolated cleft palate and submucuous cleft palate) and were recruited from the Finnish Cleft Center. We also studied associations between serum lipid fatty acids and early breast milk intake, cognitive development in terms of preschool language learning and school achievement. The fatty acid profiles of serum lipids did not differ between boys and girls. The proportion of myristic acid in serum cholesteryl esters (CE) was higher and proportion of nervonic acid in phospholipids (PL) lower in children with isolated palatal clefts than in those with submucuous clefts. Out of the present children, 30% and 60% received breast milk less than 1 or 3 months, respectively. The proportions of docosahexaenoic acid in CE and in PL were significantly higher in the children whose breast milk intake was longer than 3 months. The number of children requiring special education was higher among those who received breast milk less than 1 month than among those with longer breast milk intake. In conclusion, the fatty acid profiles of serum lipids seem to be comparable among children with different cleft types. Short breast milk intake was associated with poorer school performance.     

Interactive skills of infants with their high-risk mothers

In this pilot study, the interactive skills of infants with their high-risk, substance-dependent mothers were explored in residential treatment from pregnancy until the infant was 6 months of age. Fourteen mother-infant pairs were videotaped in feeding and free play situations at 6 months after birth. A comparison, low-risk group consisted of 12 ordinary Finnish mother-infant pairs with minimal clinical risks. The findings show significantly higher levels of dyadic interactive deficiencies among the high-risk mother-infant pairs compared to the low-risk pairs, displayed especially in the feeding situation as lack of mutuality and flat, empty, constricted affective tone of interaction. Also, more interactive deficiencies were found among the high-risk infants compared to the low-risk infants, but the differences were not significant. In this study, this finding might reflect the reduced amount of somatic complications and the benefits of treatment, the impacts of which were not explored. The differences between the high- and low-risk infants were displayed as more withdrawal, depressed mood and avoiding behavior and as less alertness and attentional abilities, robustness and focus on parent's emotional state among the high-risk group.     

A case study of amnion rupture sequence with acalvaria, blindness, and clefting: clinical and psychological profiles

The purpose of this article is to report the case of a 10-year-old girl born with anophthalmia, bilateral oblique facial clefts, and missing scalp and bones over the temporal and parietal areas of the cranial vault bilaterally. Early amnion rupture seems to be the most probable cause of this rare combination of anomalies. Because no similar case has been reported in the literature so far, we describe here the clinical and psychosocial history of this unusual patient, who has been able to live the intellectually and socially normal life of a blind child in spite of the major craniofacial deformities. The already completed and possible future therapeutic strategies are discussed.