Participation of stem cells from human cord blood in skeletal muscle regeneration of SCID mice

OBJECTIVE: In this report, we demonstrate the participation of human cord blood (HUCB) stem cells in the skeletal muscle regeneration of SCID (severe combined immunodeficient) mice. MATERIALS AND METHODS: The HUCB cells were labeled with the PKH26 fluorescent marker or recognized by an anti-HLA-ABC or anti-beta-2-microglobulin antibody. The HUCB cells were implanted directly into the damaged mouse muscle. The regeneration process and the implanted HUCB cells were traced each day after the damage, throughout a period of 7 days, and additionally at day 30 with the use of flow cytometry and confocal microscopy. RESULTS: The PKH26-labeled cells isolated from the regenerating muscle were positive for the anti-HLA-ABC antibody. The percentage of the PKH26(+) and HLA-ABC(+) cells decreased from day 1 to day 5. In the regenerating muscle, the percentage of the HLA-ABC(+) cells increased, as measured on days 7 and 30. Moreover, myofibers containing fragments of the PKH26-labeled sarcolemma were noticed. Labeling with the anti-human beta(2)-microglobulin antibody showed the presence of positive cells and myofibers at day 7 of the regeneration, suggesting fusion of human and mouse cells. CONCLUSIONS: We suggest that the HUCB cells implanted into the damaged muscle are present there for at least 30 days and that they participate in the muscle regeneration. Moreover, our study shows that the implanted HUCB cells form human muscle precursor cells residing in the repaired mouse muscle. We suggest that the HUCB cell circulation after transplantation depends on SDF-1 (stromal-derived factor-1) expression in regenerating muscle.     

Function of the DEMETER DNA glycosylase in the Arabidopsis thaliana male gametophyte

In double fertilization, the vegetative cell of the male gametophyte (pollen) germinates and forms a pollen tube that brings to the female gametophyte two sperm cells that fertilize the egg and central cell to form the embryo and endosperm, respectively. The 5-methylcytosine DNA glycosylase DEMETER (DME), expressed in the central cell, is required for maternal allele demethylation and gene imprinting in the endosperm. By contrast, little is known about the function of DME in the male gametophyte. Here we show that reduced transmission of the paternal mutant dme allele in certain ecotypes reflects, at least in part, defective pollen germination. DME RNA is detected in pollen, but not in isolated sperm cells, suggesting that DME is expressed in the vegetative cell. Bisulfite sequencing experiments show that imprinted genes (MEA and FWA) and a repetitive element (Mu1a) are hypomethylated in the vegetative cell genome compared with the sperm genome, which is a process that requires DME. Moreover, we show that MEA and FWA RNA are detectable in pollen, but not in isolated sperm cells, suggesting that their expression occurs primarily in the vegetative cell. These results suggest that DME is active and demethylates similar genes and transposons in the genomes of the vegetative and central cells in the male and female gametophytes, respectively. Although the genome of the vegetative cell does not participate in double fertilization, its DME-mediated demethylation is important for male fertility and may contribute to the reconfiguration of the methylation landscape that occurs in the vegetative cell genome.     

Rearranged EML4-ALK fusion transcripts sequester in circulating blood platelets and enable blood-based crizotinib response monitoring in non-small-cell lung cancer

Purpose: Non-small-cell lung cancers harboring EML4-ALK rearrangements are sensitive to crizotinib. However, despite initial response, most patients will eventually relapse, and monitoring EML4-ALK rearrangements over the course of treatment may help identify these patients. However, challenges associated with serial tumor biopsies have highlighted the need for blood-based assays for the monitoring of biomarkers. Platelets can sequester RNA released by tumor cells and are thus an attractive source for the non-invasive assessment of biomarkers. Methods: EML4-ALK rearrangements were analyzed by RT-PCR in platelets and plasma isolated from blood obtained from 77 patients with non-small-cell lung cancer, 38 of whom had EML4-ALK-rearranged tumors. In a subset of 29 patients with EML4-ALK-rearranged tumors who were treated with crizotinib, EML4-ALK rearrangements in platelets were correlated with progression-free and overall survival. Results: RT-PCR demonstrated 65% sensitivity and 100% specificity for the detection of EML4-ALK rearrangements in platelets. In the subset of 29 patients treated with crizotinib, progression-free survival was 3.7 months for patients with EML4-ALK+ platelets and 16 months for those with EML4-ALK− platelets (hazard ratio, 3.5; P = 0.02). Monitoring of EML4-ALK rearrangements in the platelets of one patient over a period of 30 months revealed crizotinib resistance two months prior to radiographic disease progression. Conclusions: Platelets are a valuable source for the non-invasive detection of EML4-ALK rearrangements and may prove useful for predicting and monitoring outcome to crizotinib, thereby improving clinical decisions based on radiographic imaging alone.     

Heterogeneous Mixture of Amniotic Cells is Likely a Better Source of Stem Cells than Adipose Tissue

Archivum Immunologiae et Therapiae Experimentalis - Stem cells are increasingly being used in the course of burn treatment. As several different types of stem cells are available for the purposes,...     

What Is the Role of Therapeutic Plasma Exchange as an Adjunctive Treatment in Severe COVID-19: A Systematic Review

Introduction: Since the COVID-19 pandemic outbreak, multiple promising treatment modalities have been tested, however, only several of them were proven to be effective. Therapeutic plasma exchange (TPE) has been recently discussed as a possible supportive treatment for severe cases. Methods: To investigate a possible role of TPE in severe COVID-19 we used a structured systematic search strategy to retrieve all relevant publications in the field. We screened in PubMed, EMBASE, Web of Science, Cochrane Library and clinicaltrials.gov for data published until the 4 June 2021. Results: We identified 18 papers, enrolling 384 patients, 220 of whom received TPE. The number of TPE sessions ranged from 1 to 9 and the type of replacement fluid varied markedly between studies (fresh frozen plasma or 5% albumin solution, or convalescent plasma). Biochemical improvement was observed in majority of studies as far as C-reactive protein (CRP), interleukin-6 (IL-6), ferritin, lactate dehydrogenase (LDH), D-dimer concentrations and lymphocyte count are concerned. The improvement at a laboratory level was associated with enhancement of respiratory function. Adverse effects were limited to five episodes of transient hypotension and one femoral artery puncture and thrombophlebitis. Conclusions: Although the effect of therapeutic plasma exchange on mortality remains unclarified, the procedure seems to improve various secondary end-points such as PaO₂/FiO₂ ratio or biomarkers of inflammation. Therapeutic plasma exchange appears to be a safe treatment modality in COVID-19 patients in terms of side effects.     

Orbital nerve sheath myxoma: a case report

A 72-year-old man was referred to the Service of Ophthalmology due to a 2-year history of ptosis and a painless mass in the lateral orbital margin of the right eye. Orbital MRI revealed a well-demarcated lesion in the superotemporal quadrant of the orbit. After surgical excision, histopathological examination led to the diagnosis of nerve sheath myxoma, a tumor composed of myxoid nodules separated by fibrous septa with spindle-shaped and stellate cells. Many of these cells were immunostained with antibodies to S-100 protein. This is the first case reported in the literature of such a tumor located in the orbit, and, though extremely rare, it should be considered in the differential diagnosis of orbital tumors.     

Abnormalities in the hair morphology of patients with some but not all types of mucopolysaccharidoses

Mucopolysaccharidoses (MPS) are a group of inherited, progressive, metabolic diseases, caused by the deficiency of one of the enzymes involved in the degradation of glycosaminoglycans (GAGs). The disease is usually fatal, with the life span of most untreated MPS patients being between one and two decades. In this report, on the basis of scanning electron microscopy (SEM) studies, we demonstrate that, besides the many other symptoms of MPS, there are characteristic abnormalities in the hair morphology of patients suffering from some types of this disease (MPS I, MPS II, MPS IIIA, MPS IIIB), but not from other types (MPS IVA, MPS IVB, MPS VI), where the changes are minor, if any. Different GAGs accumulate in the tissues of patients suffering from the various MPS types, and analysis of the disease types in which severe hair abnormalities occur or not could suggest that the accumulation of heparan sulfate, rather than dermatan sulfate or keratan sufate, may be responsible for the major changes in hair morphology. Considerable abnormalities in hair morphology occur in patients suffering from MPS I, MPS II, MPS IIIA, and MPS IIIB, but not in patients suffering from MPS IVA, MPS IVB, and MPS VI; this feature might potentially be used as an additional test for the assessment of the efficacy of treatments for MPS patients (types I, II, IIIA, and IIIB).     

Uveal melanoma in a 19-month-old child

Uveal melanoma is extremely rare in children. Its clinical and histopathological features have been reported to be similar to those observed in adults. The tumor usually presents as a sessile or dome-shaped mass with secondary nonrhegmatogenous retinal detachment. We report a 19-month-old boy with a choroidal melanoma presenting as hemorrhagic retinal detachment and buphthalmos. The eye was enucleated, but the child subsequently died from systemic metastases.