EBioMedicine
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Comparative Study
Development of Upper Respiratory Tract Microbiota in Infancy is Affected by Mode of Delivery.
Birth by Caesarian section is associated with short- and long-term respiratory morbidity. We hypothesized that mode of delivery affects the development of the respiratory microbiota, thereby altering its capacity to provide colonization resistance and consecutive pathobiont overgrowth and infections. ⋯ Within the first week, rapid niche differentiation had occurred; initially with in most infants Staphylococcus aureus predominance, followed by differentiation towards Corynebacterium pseudodiphteriticum/propinquum, Dolosigranulum pigrum, Moraxella catarrhalis/nonliquefaciens, Streptococcus pneumoniae, and/or Haemophilus influenzae dominated communities. Infants born by Caesarian section showed a delay in overall development of respiratory microbiota profiles with specifically reduced colonization with health-associated commensals like Corynebacterium and Dolosigranulum, thereby possibly influencing respiratory health later in life.
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Parkinson's disease is a common neurodegenerative disorder, which is due to the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and for which no definitive cure is currently available. Cellular functions in mouse and human tissues can be restored after fusion of bone marrow (BM)-derived cells with a variety of somatic cells. Here, after transplantation of hematopoietic stem and progenitor cells (HSPCs) in the SNpc of two different mouse models of Parkinson's disease, we significantly ameliorated the dopaminergic neuron loss and function. ⋯ Interestingly, the hybrids can undergo reprogramming in vivo and survived up to 4weeks after transplantation, while acquiring features of mature astroglia. These newly generated astroglia produced Wnt1 and were essential for functional rescue of the dopaminergic neurons. Our data suggest that glial-derived hybrids produced upon fusion of transplanted HSPCs in the SNpc can rescue the Parkinson's disease phenotype via a niche-mediated effect, and can be exploited as an efficient cell-therapy approach.
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Angiosarcomas are rare malignant tumors of vascular origin that represent a genuine therapeutic challenge. Recently, the combination of metronomic chemotherapy and drug repositioning has been proposed as an attractive alternative for cancer patients living in developing countries. ⋯ This study was funded by institutional and philanthropic grants.
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Multicenter Study
Biomarkers for Early Diagnostic of Mild Cognitive Impairment in Type-2 Diabetes Patients: A Multicentre, Retrospective, Nested Case-Control Study.
Both type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) are common age-associated disorders and T2DM patients show an increased risk to suffer from AD, however, there is currently no marker to identify who in T2DM populations will develop AD. Since glycogen synthase kinase-3β (GSK-3β) activity, ApoE genotypes and olfactory function are involved in both T2DM and AD pathogenesis, we investigate whether alterations of these factors can identify cognitive impairment in T2DM patients. ⋯ Aging, activation of peripheral circulating GSK-3β, expression of ApoE ε4 and increase of olfactory score are diagnostic for the mild cognitive impairment in T2DM patients, and combination of these biomarkers can improve the diagnostic accuracy.
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Cerebrospinal fluid (CSF) neurofilament light chain protein (NFL) is a sensitive marker of neuronal injury in a variety of neurodegenerative conditions, including the CNS dysfunction injury that is common in untreated HIV infection. However, an important limitation is the requirement for lumbar puncture. For this reason, a sensitive and reliable blood biomarker of CNS injury would represent a welcome advance in both clinical and research settings. ⋯ These results show that plasma NFL may prove a valuable tool to evaluate ongoing CNS injury in HIV infection that may be applied in the clinic and in research settings to assess the presence if active CNS injury. Because CSF NFL is also elevated in a variety of other CNS disorders, sensitive measures of plasma NFL may similarly prove useful in other settings.