Human intrathymic lineage commitment is marked by differential CD7 expression: identification of CD7- lympho-myeloid thymic progenitors

The identity and lineage potential of the cells that initiate thymopoiesis remain controversial. The goal of these studies was to determine, at a clonal level, the immunophenotype and differentiation pathways of the earliest progenitors in human thymus. Although the majority of human CD34(+)lin(-) thymocytes express high levels of CD7, closer analysis reveals that a continuum of CD7 expression exists, and 1% to 2% of progenitors are CD7(-). CD34(+)lin(-) thymocytes were fractionated by CD7 expression and tested for lineage potential in B-lymphoid, T-lymphoid, and myeloid-erythroid conditions. Progressive restriction in lineage potential correlated with CD7 expression, that is, the CD7(hi) fraction produced T and NK cells but lacked B and myelo-erythroid potential, the CD7(int) (CD10(+)) fraction produced B, T, and NK cells, but lacked myelo-erythroid potential. The CD7(-) fraction produced all lymphoid and myelo-erythroid lineages and expressed HSC-associated genes. However, CD34(+)lin(-)CD7(-) thymocytes also expressed early T lymphoid genes Tdt, pTalpha, and IL-7Ralpha and lacked engraftment capacity, suggesting the signals that direct lymphoid commitment and corresponding loss of HSC function are rapidly initiated on arrival of HSC in the human thymus. Thus, differential levels of CD7 identify the progressive stages of lineage commitment in human thymus, initiated from a primitive CD7(-) lympho-myeloid thymic progenitor.     

Use of argon plasma coagulation in advanced cancers of the upper digestive tract

Endoscopy being a diagnostic tool, allows also a nonsurgical treatment of upper gastrointestinal tract neoplasms, even at their advanced stage. Argon plasma coagulation (APC) is a contact-free method of monopolar coagulation, based primarily on the effects of high frequency electrical current flow in the ionized argon. The study used in 14 patients, aged 56-85 years, with advanced carcinoma of oesophagus and/or cardia. Carcinoma was diagnosed upon the results of endoscopic and microscopic examinations. The following parameters were included in the analysis: electrical current power, number of treatment sessions, stage of dysphagia, oesophagus passage, localization and type of a tumor. The analysis revealed that APC is a highly effective as well as safe method of palliative treatment of advanced oesophageal and/or cardiac cancers. Moreover, it was noted that APC is more effective in adenocarcinomas than in squamous cell carcinomas.     

Does Nordic walking improves the postural control and gait parameters of women between the age 65 and 74: a randomized trial

[Purpose] To assess the effect of 12-weeks Nordic walking training on gait parameters and some elements of postural control. [Subjects and Methods] Sixty-seven women aged 65 to 74 years were enrolled in this study. The subjects were divided into a Nordic Walking group (12 weeks of Nordic walking training, 3 times a week for 75 minutes) and a control group. In both study groups, a set of functional tests were conducted at the beginning and at the end of the study: the Forward Reach Test (FRT) and the Upward Reach Test (URT) on a stabilometric platform, and the analysis of gait parameters on a treadmill. [Results] The NW group showed improvements in: the range of reach in the FRT test and the URT test in compared to the control group. The length of the gait cycle and gait cycle frequency also showed changes in the NW group compared to the control group. [Conclusion] A 12-week NW training program had a positive impact on selected gait parameters and may improve the postural control of women aged over 65 according to the results selected functional tests.Key words: Nordic walking, Postural control, Gait     

Renal Mechanisms of Association between Fibroblast Growth Factor 1 and Blood Pressure

The fibroblast growth factor 1 (FGF1) gene is expressed primarily in the kidney and may contribute to hypertension. However, the biologic mechanisms underlying the association between FGF1 and BP regulation remain unknown. We report that the major allele of FGF1 single nucleotide polymorphism rs152524 was associated in a dose-dependent manner with systolic BP (P=9.65×10⁻⁵) and diastolic BP (P=7.61×10⁻³) in a meta-analysis of 14,364 individuals and with renal expression of FGF1 mRNA in 126 human kidneys (P=9.0×10⁻³). Next-generation RNA sequencing revealed that upregulated renal expression of FGF1 or of each of the three FGF1 mRNA isoforms individually was associated with higher BP. FGF1-stratified coexpression analysis in two separate collections of human kidneys identified 126 FGF1 partner mRNAs, of which 71 and 63 showed at least nominal association with systolic and diastolic BP, respectively. Of those mRNAs, seven mRNAs in five genes (MME, PTPRO, REN, SLC12A3, and WNK1) had strong prior annotation to BP or hypertension. MME, which encodes an enzyme that degrades circulating natriuretic peptides, showed the strongest differential coexpression with FGF1 between hypertensive and normotensive kidneys. Furthermore, higher level of renal FGF1 expression was associated with lower circulating levels of atrial and brain natriuretic peptides. These findings indicate that FGF1 expression in the kidney is at least under partial genetic control and that renal expression of several FGF1 partner genes involved in the natriuretic peptide catabolism pathway, renin-angiotensin cascade, and sodium handling network may explain the association between FGF1 and BP.     

Adipose‐derived stem cells and keratinocytes in a chronic wound cell culture model: the role of hydroxyectoine

Chronic wounds represent a major socio‐economic problem in developed countries today. Wound healing is a complex biological process. It requires a well‐orchestrated interaction of mediators, resident cells and infiltrating cells. In this context, mesenchymal stem cells and keratinocytes play a crucial role in tissue regeneration. In chronic wounds these processes are disturbed and cell viability is reduced. Hydroxyectoine (HyEc) is a membrane protecting osmolyte with protein and macromolecule stabilising properties. Adipose‐derived stem cells (ASC) and keratinocytes were cultured with chronic wound fluid (CWF) and treated with HyEc. Proliferation was investigated using MTT test and migration was examined with transwell‐migration assay and scratch assay. Gene expression changes of basic fibroblast growth factor (b‐FGF), vascular endothelial growth factor (VEGF), matrix metalloproteinases‐2 (MMP‐2) and MMP‐9 were analysed by quantitative real‐time polymerase chain reaction (qRT‐PCR). CWF significantly inhibited proliferation and migration of keratinocytes. Addition of HyEc did not affect these results. Proliferation capacity of ASC was not influenced by CWF whereas migration was significantly enhanced. HyEc significantly reduced ASC migration. Expression of b‐FGF, VEGF, MMP‐2 and MMP‐9 in ASC, and b‐FGF, VEGF and MMP‐9 in keratinocytes was strongly induced by chronic wound fluid. HyEc enhanced CWF induced gene expression of VEGF in ASC and MMP‐9 in keratinocytes. CWF negatively impaired keratinocyte function, which was not influenced by HyEc. ASC migration was stimulated by CWF, whereas HyEc significantly inhibited migration of ASC. CWF induced gene expression of VEGF in ASC and MMP‐9 in keratinocytes was enhanced by HyEc, which might partly be explained by an RNA stabilising effect of HyEc.     

Hemorrhagic stroke in a patient requiring long-term anticoagulant treatment

Hemorrhagic stroke is a frequent cause of morbidity and mortality in Poland. It results from disruption of intracranial vessel wall continuity. We report a case of 66-years-old man with prosthetic aortic valve after three ischemic strokes treated with acenocoumarol who was admitted to hospital with vertigo and motoric aphasia. Computed tomography confirmed a hemorrhagic stroke related to anticoagulant treatment. We discussed the principles of management and therapeutic options in patients requiring long-term anticoagulation suffering from severe hemorrhagic complications.     

Very small embryonic-like stem cells: characterization, developmental origin, and biological significance

Bone marrow (BM) was, for many years, primarily envisioned as the "home organ" of hematopoietic stem cells (HSC). Augmenting evidence demonstrates, however, that BM, in addition to HSC, also contains a heterogeneous population of non-HSC. Recently, our group identified in BM and other adult tissues a population of very small embryonic-like stem cells (VSELs), which express several markers characteristic for pluripotent stem cells that are characteristic for epiblast/germ line-derived stem cells. Thus, we hypothesize that VSELs are a population of epiblast-derived cells that are deposited during early gastrulation in developing tissues/organs and play an important role in turnover of tissue-specific/committed stem cells. In this context, VSELs deposited in BM can give rise to long-term repopulating HSC. VSELs could be also mobilized into peripheral blood (PB), and the number of these cells circulating in PB increases during stress and tissue/organ injuries. Finally, we envision that in pathological situations VSELs are involved in development of some malignancies (e.g., teratomas, germinal tumors).