Dental pulp stem cells: Novel cell-based and cell-free therapy for peripheral nerve repair

The regeneration of peripheral nerves comprises complicated steps involving a set of cellular and molecular events in distal nerve stumps with axonal sprouting and remyelination. Stem cell isolation and expansion for peripheral nerve repair(PNR) can be achieved using a wide diversity of prenatal and adult tissues, such as bone marrow or brain tissues. The ability to obtain stem cells for cell-based therapy(CBT) is limited due to donor site morbidity and the invasive nature of the harvesting process. Dental pulp stem cells(DPSCs) can be relatively and simply isolated from the dental pulps of permanent teeth, extracted for surgical or orthodontic reasons. DPSCs are of neural crest origin with an outstanding ability to differentiate into multiple cell lineages. They have better potential to differentiate into neural and glial cells than other stem cell sources through the expression and secretion of certain markers and a range of neurotropic factors;thus, they should be considered a good choice for PNR using CBT. In addition,these cells have paracrine effects through the secretion of neurotrophic growth factors and extracellular vesicles, which can enhance axonal growth and remyelination by decreasing the number of dying cells and activating local inhabitant stem cell populations, thereby revitalizing dormant or blocked cells,modulating the immune system and regulating inflammatory responses. The use of DPSC-derived secretomes holds great promise for controllable and manageable therapy for peripheral nerve injury. In this review, up-to-date information about the neurotrophic and neurogenic properties of DPSCs and their secretomes is provided.     

Metabolism-Associated Markers and Childhood Autism Rating Scales (CARS) as a Measure of Autism Severity

Autism spectrum disorder (ASD) is a neuro-behavioral syndrome with a broad spectrum of different mechanisms and etiologies that are caused by abnormal brain development. To date, no highly reliable and effective diagnostic biomarker to assess ASD is available so far. The present study investigated the predictivity potential of some suggested markers in ASD diagnosis focusing onto the relative ratios of several plasma biomarkers of electron transport chain function, and mitochondrial metabolism in 41 patients with ASD evaluated for behavior deficits measured using Childhood Autism Rating Scales (CARS). The control matched for further 41 healthy subjects. The relation of these relative ratios to ASD severity was also examined, as well as their ability to distinguish ASD children from neurotypical children. All predictive ratios were found to be markedly altered and correlated in ASD patients. However, no ratio was connected with autism severity. Interestingly, MRCC-I/caspase-7, GSH/GST, and MRCC-I/COQ10 were the most distinctive relative ratios between neurotypical controls and ASD patients and may thereby be useful biomarkers for early diagnosis of ASD. Overall, this investigation proves that relative ratios of numerous mitochondrial biomarkers might be predictive and efficient to differentiate between neurotypical children and ASD.     

Comparative functional morphology of the mouth brushes of mosquito larvae (Diptera: Culicidae)

Structural and morphological features of the feeding brushes of fourth instars of four species of mosquitoes were studied using light and scanning electron microscopes. The fine structure of the elements of the lateral palatal brushes, anteromedian palatal brushes, mandibular brushes and combs, and maxillary brushes of each species was investigated and related to feeding behavior. The movement of the mouth brushes in living larvae was observed by stereomicroscopy under laboratory conditions. Mouth brush function and morphology varied among the species studied. The brushes of Culex quinquefasciatus Say, Cx. tarsalis Coquillett, and Aedes aegypti L. were more complex than those of Anopheles albimanus Wiedemann. The main role of the filaments of the lateral palatal brushes (LPB) was to generate and maintain water and particle flow around the larval head. In Ae. aegypti, most of the LPB filaments were provided with stout pointed teeth at the tips which were useful in the brushing of food material. In An. albimanus, the LPB filaments were simple and very closely packed and were used to stir the water surface film to direct the floating materials into the area of the mouth opening. The filaments of the anteromedian palatal brush (APBr) in the Culex species were branched. In Ae. aegypti, the APBr contained long bladelike filaments and short teethlike elements, whereas in An. albimanus, the APBr filaments were all long and bladelike. The morphological structure of the spicules and setae of the mandibular brushes and combs and the maxillary brushes are described. The main function of these brushes is to direct and concentrate particle flow.     

Hypopigmented mycosis fungoides: frequent expression of a CD8+ T-cell phenotype

Hypopigmented mycosis fungoides (MF) is a form of cutaneous T-cell lymphoma in which hypopigmentation occurs in the absence of classic lesions of MF. Hypopigmented MF predominantly affects people with dark complexions. The natural history of this variant of cutaneous T-cell lymphoma is similar to that of conventional MF, although the disease onset is usually in childhood or adolescence. In a retrospective study we evaluated the clinical, histopathologic, immunohistochemical, and molecular characteristics of hypopigmented MF in 15 patients. Similar to other reports, the disease onset occurred in childhood and adolescence in most of the cases. The survival rate was comparable with that of classic MF. We did not observe progression to systemic disease or lymph node involvement. Histopathologically hypopigmented lesions were indistinguishable from hyperpigmented or erythematous patches. On immunohistochemical analysis a predominantly CD8+ infiltrate was detected in the majority of cases (nine of 15 patients). To determine whether epidermotropic CD8+ T cells represent the malignant T-cell clone or whether these cells are innocent, tumor-infiltrating T lymphocytes, we performed microdissection of epidermotropic CD8+ T cells and analyzed T-cell receptor-gamma chain gene for rearrangements. The epidermotropic CD8+ T lymphocytes showed clonal T-cell receptor gene rearrangement and therefore represented the malignant T-cell clone. We conclude that hypopigmented MF tends to occur in young people and that it belongs to the group of CD8+ cutaneous T-cell lymphomas in the majority of cases.     

The impact of HIV infection and immunodeficiency on human papillomavirus type 6 or 11 infection and on genital warts

BACKGROUND: HIV infection and associated immunodeficiency are known to alter the course of human papillomavirus (HPV) infections and of associated diseases. GOAL: This study investigated the association between HIV and HPV and genital warts. STUDY DESIGN: HPV testing and physical examinations were performed in two large prospective studies: the Women's Interagency HIV Study (WIHS) and the HIV Epidemiology Research Study (HERS). Statistical methods incorporating dependencies of longitudinal data were used to examine the relationship between HIV and HPV and genital warts. RESULTS: A total of 1008 HIV-seronegative and 2930 HIV-seropositive women were enrolled in the two studies. The prevalence of HPV 6 or 11 was 5.6 times higher in HIV-seropositive women in the WIHS and 3.6 times higher in the HERS. Genital wart prevalence increased by a factor of 3.2 in the WIHS and 2.7 in the HERS in HIV-seropositive women. In the WIHS, infection with HPV type 6 or 11, in comparison with no HPV infection, was associated with odds of genital wart prevalence of 5.1 (95% CI: 2.9-8.8), 8.8 (95% CI: 6.1-12.8), and 12.8 (95% CI: 8.8-18.8) in HIV-seronegative women, HIV-seropositive women with > or =201 CD4 cells/microl, and HIV-seropositive women with < or =200 CD4 cells/microl, respectively. In the HERS, infection with HPV type 6 or 11 was associated with odds of 2.7 (95% CI: 1.6-4.6), 4.9 (95% CI: 3.2-7.7), and 5.3 (95% CI: 3.3-8.5) in these same groups. Other HPV types showed a similar dose-response relation, but of substantially lower magnitude and statistical significance. CONCLUSIONS: HIV infection and immunodeficiency synergistically modified the relation between HPV 6 or 11 infection and genital wart prevalence.