Abramsochoa1213

As a refractory fibrosis disease, intrauterine adhesions (IUAs) is defined as fibrosis of the physiological endometrium. Although hysteroscopic adhesiolysis is widely recommended as an effective treatment, prognosis and recurrence remain poor in severe cases. Recently, stem cell therapy has been promoted as a promising treatment for IUAs. The ability of human amniotic epithelial cells (hAECs), emerging as a new candidate for stem cell therapy, to treat IUAs has not been demonstrated. To study the potential effects of hAECs on IUAs, we created an IUA rat model using mechanical injury and injected cultured primary hAECs into the rats' uteri. Next, we observed the morphological structure of endometrial thickness and glands using hematoxylin and eosin staining, and we detected extracellular-matrix collagen deposition using Masson staining. In addition, we performed immunohistochemical staining and reverse-transcription polymerase chain reaction (RT-PCR) to investigate potential fibrosis molecules and angiogenesis factors 7 d after hAECs transplantation. Finally, we detected estrogen receptor (ER) and growth factors via RT-PCR to verify the molecular mechanism underlying cell therapy. In the IUA rat models, endometrial thickness and endometrial glands proliferated and collagen deposition decreased significantly after hAEC transplantation. We found that during the recovery of injured endometrium, the crucial fibrosis marker transforming growth factor-β (TGF-β) was regulated and angiogenesis occurred in the endometrial tissue with the up-regulation of vascular endothelial growth factor. Furthermore, hAECs were shown to promote ER expression in the endometrium and regulate the inflammatory reaction in the uterine microenvironment. In conclusion, these results demonstrated that hAEC transplantation could inhibit the progression of fibrosis and promote proliferation and angiogenesis in IUA rat models. The current study suggests hAECs as a novel stem cell candidate in the treatment of severe IUA.The foot seems to demonstrate considerable power absorption and generation characteristics during running. These have been mainly accounted to the mechanics of the ankle joint, however, evidence suggests that joint kinetics have been overestimated by single-segment foot models. The scope of the present study was to estimate the energetics of the ankle-, chopart-, lisfranc- and hallux joint during heel-strike running. Power absorption and generation occuring at different segments of the foot of seven asymptomatic adults was modelled using a four-segment kinetic foot model. Participants ran barefoot with an average running speed 3.5 m/s along a 10 meter walkway. The peak power generation of the ankle, chopart, lisfranc, and hallux joint reached respectively an average of 13.9, 4.12, 1.08 and 0.32 Watt/kg. The Lisfranc joint showed poor power absorption compared to the other three joints. It was further demonstrated that the Ankle and Chopart joints seem to have both receptive and propulsive characteristics. The behavior of the Lisfranc joint complied almost exclusively with propulsive characteristics. Finally, it can be concluded that the midfoot accounts for approximately 25% of the total power absorption occuring at the foot joints and not 50% as initially hypothesized.Cellular senescence, a permanent arrest of cell proliferation, is characterized by a senescence-associated secretory phenotype (SASP), which reinforces senescence and exerts noxious effects on adjacent cells. Screening Library Recent studies suggest that transplanting small numbers of senescent cells suffices to provoke tissue inflammation. We hypothesized that senescent cells can directly augment renal injury. Primary scattered tubular-like cells (STC) acquired from pig kidneys were irradiated by 10Gy of cesium radiation, and 3 weeks later cells were characterized for levels of senescence and SASP markers. Control or senescent (SEN) STC were then pre-labeled and injected (5X105 cells) into the aorta of C57BL/6J mice. Four weeks later, renal oxygenation was studied in-vivo using 16.4T magnetic resonance imaging, and function by plasma creatinine level. Renal markers of SASP, fibrosis, and microvascular density were evaluated ex-vivo. Per flow cytometry, irradiation induced senescence in 80-99% of STC, which showed increased gene expression of senescence and SASP markers, SA-ß-gal staining, and cytokines levels (especially IL-6) secreted in conditioned-medium. Four weeks after injection, cells were detected engrafted in the mouse kidneys with no evidence for rejection. Plasma creatinine and renal tissue hypoxia increased in SEN compared to control. SEN kidneys were more fibrotic, with fewer CD31+ endothelial cells, and showed upregulation of IL-6 gene expression. Therefore, exogenously delivered senescent renal STC directly injure healthy mouse kidneys. Additional studies are needed to determine the role of endogenous cellular senescence in the pathogenesis of kidney injury, and evaluate the utility of senolytic therapy.Loss-of-function mutations in phospholipase C epsilon (PLCE1) have been detected in patients with nephrotic syndrome, but other family members with the same mutation were asymptomatic, suggesting additional stressor are required to cause the full phenotype. Consistent with these observations, we determined that global Plce1-deficient mice have histologically normal glomeruli and no albuminuria at baseline. Angiotensin II (Ang II) is known to induce glomerular damage in genetically susceptible individuals. Therefore, we tested whether Ang II enhances glomerular damage in Plce1-deficient mice. Ang II increased blood pressure equally in Plce1-deficient and wildtype littermates. Additionally, it led to twenty-fold increased albuminuria and significantly more sclerotic glomeruli in Plce1-deficient mice compared to wildtype littermates. Furthermore, Plce1-deficient mice demonstrated diffuse mesangial expansion, podocyte loss and focal podocyte foot process effacement. To determine whether these effects are mediated by hypertension and hyperfiltration, rather than directly through Ang II, we raised blood pressure to a similar level using DOCA+salt+uninephrectomy and norepinephrine. This caused a five-fold increase in albuminuria in Plce1-/- mice and a significant increase in the number of sclerotic glomeruli. Consistent with previous findings in mice, we detected strong PLCE1 transcript expression in podocytes using single-cell sequencing of human kidney tissue. In hemagglutinin-tagged Plce1 transgenic mice, Plce1 was detected in podocytes and also in glomerular arterioles using immunohistochemistry. Our data demonstrate that Plce1-deficiency in mice predisposes to glomerular damage secondary to hypertensive insults.