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IntroductionTopical administration of eye drops is the major route for drug delivery to the cornea. Orbital fat-derived stem cells (OFSCs) possess an in vitro corneal epithelial differentiation capacity. Both the safety and immunomodulatory ability of systemic OFSC transplantation were demonstrated in our previous work. In this study, we investigated the safety, therapeutic effect, and mechanism(s) of topical OFSC administration in an extensive alkali-induced corneal wound.MethodsCorneal injury was created by contact of a piece of 0.5 N NaOH-containing filter paper on the corneal surface of a male Balb/c mouse for 30 s. The area of the filter paper covered the central 70% or 100% of the corneal surface. OFSCs (2 × 105) in 5 μl phosphate-buffered saline (PBS) were given by topical administration (T) twice a day or by two intralimbal (IL) injections in the right cornea, while 5 μl of PBS in the left cornea served as the control.ResultsTopical OFSCs promoted corneal re-epithelialization of both the limbal-sparing and limbal-involved corneal wounds. In the first three days, topical OFSCs significantly reduced alkali-induced corneal edema and stromal infiltration according to a histopathological examination. Immunohistochemistry and immunofluorescence staining revealed that transplanted cells were easily detectable in the corneal epithelium, limbal epithelium and stroma, but only some of transplanted cells at the limbal epithelium had differentiated into cytokeratin 3-expressing cells. OFSCs did not alter neutrophil (Ly6G) levels in the cornea, but significantly reduced macrophage (CD68) infiltration and inducible nitrous oxide synthetase (iNOS) production during acute corneal injury as quantified by a Western blot analysis. Continuous topical administration of OFSCs for seven days improved corneal transparency, and this was accompanied by diffuse stromal engraftment of transplanted cells and differentiation into p63-expressing cells at the limbal area. The therapeutic effect of the topical administration of OFSCs was superior to that of the IL injection. OFSCs from the IL injection clustered in the limbal area and central corneal epithelium, which was associated with a persistent corneal haze.ConclusionsTopical OFSC administration is a simple, non-surgical route for stem cell delivery to promote corneal tissue regeneration through ameliorating acute inflammation and corneal epithelial differentiation. The limbal area serves as a niche for OFSCs differentiating into corneal epithelial cells in the first week, while the stroma is a potential site for anti-inflammation of OFSCs. Inhibition of corneal inflammation is related to corneal transparency.

EA could be useful for reducing uterine artery blood flow impedance, but did not increase the pregnancy rate in patients undergoing IVF.

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Mesenchymal stromal cells (MSCs) have great potential to maintain glucose homeostasis and metabolic balance. Here, we demonstrate that in mice continuously fed with high-fat diet (HFD) that developed non-insulindependent diabetes, two episodes of systemic MSC transplantations effectively improve glucose tolerance and blood glucose homeostasis and reduce body weight through targeting pancreas and insulin-sensitive tissues and organs via site-specific mechanisms. MSCs support pancreatic islet growth by direct differentiation into insulin-producing cells and by mitigating the cytotoxicity of interleukin 1 (IL-1) and tumor necrosis factor-a (TNF-a) in the pancreas. Localization of MSCs in the liver and skeletal muscles in diabetic animals is also enhanced and therefore improves glucose tolerance, although long-term engraftment is not observed. MSCs prevent HFD-induced fatty liver development and restore glycogen storage in hepatocytes. Increased expression of IL-1 receptor antagonist and Glut4 in skeletal muscles after MSC transplantation results in better blood glucose homeostasis. Intriguingly, systemic MSC transplantation does not alter adipocyte number, but it decreases HFD-induced cell infiltration in adipose tissues and reduces serum levels of adipokines, including leptin and TNF-a. Taken together, systemic MSC transplantation ameliorates HFD-induced obesity and restores metabolic balance through multisystemic regulations that are niche dependent. Such findings have supported systemic transplantation of MSCs to correct metabolic imbalance.Impairment of glucose tolerance and insulin resistance initiates type 2 diabetes; however, exhaustion of the insulin supply due to b-cell apoptosis is the ultimate pathomechanism of both type 1 and 2 diabetes (1,2). The liver, adipose tissues, skeletal muscles, and vascular tissues are insulin-sensitive tissues responsible for blood glucose homeostasis (1,3). Inflammation adversely affects insulin sensitivity and worsens diabetic retinopathies, neuropathies, and vasculopathies (4-6). Proinflammatory cytokines produced by macrophages, such as tumor necrosis factor-a (TNF-a) and interleukin 1 (IL-1), create a vicious cycle of reduced insulin sensitivity (3,(7)(8)(9).To the present, more than 300 clinical trials of mesenchymal stem/stromal cell (MSC) transplantations have been conducted worldwide with a wide clinical application targeting more than 50 indications (www.clinicaltrials.gov). Systemic transplantation is the most favorable route for MSC delivery from a safety and systemic regulation point of view, and 56% of MSC clinical trials are allogenic transplantation (10). It is well accepted that the majority of MSCs are initially distributed in vital organs (11-16) and are also frequently found in tissues of mesenchymal origin (11,12) when systemically administered. Nevertheless, the long-term engraftment of MSCs is minimal, and the engraftment rate is not correlated with therapeutic response in human studies (17). The acutely diseased and damaged tissues show increased loca...

Extended-field IMRT of 40 Gy to the PALN plus concurrent cisplatin can effectively eradicate subclinical disease at the PALN and improve the outcome for patients with PLN-positive stage IB2-IIIB cervical cancer.

ObjectiveTo evaluate the clinical outcome and parameters related to coexisting endometrial carcinoma in women with tissue-diagnosed endometrial hyperplasia.MethodsBetween January 1991 and December 2009, three hundred and eighty-six patients with the presumptive diagnosis of endometrial hyperplasia were retrieved. Among these, one hundred and twenty-five patients were identified as having coexisting endometrial carcinoma in hysterectomy specimens. The three hundred and eighty-six patients were divided into two groups: the hyperplasia-benign group (261 cases) and the hyperplasia-malignant group (125 cases). Several clinical parameters including age, menopausal status, history of abnormal uterine bleeding, obstetrical history, medical history of diabetes and hypertension, BMI, and preoperative pathologic results were investigated.ResultsAge ≥53 (odds ratio [OR], 2.40; 95% confidence interval [CI], 1.26 to 4.57), menopausal status (OR, 2.07; 95% CI, 1.14 to 3.76), diabetes history (OR, 7.33; 95% CI, 2.79 to 19.26), abnormal uterine bleeding (OR, 3.99; 95% CI, 1.22 to 13.02), atypical endometrial hyperplasia (OR, 7.38; 95% CI, 4.03 to 13.49), and body mass index ≥27 (OR, 3.24; 95% CI, 1.76 to 5.97) were independent risk factors for prediction of endometrial hyperplasia coexisting with endometrial carcinoma. The diagnostic efficacy of atypical endometrial hyperplasia to predict the endometrial hyperplasia coexisting with endometrial carcinoma was better than or similar to those of other independent factors and combinations of these factors.ConclusionCoexisting malignancy should be considered when examining endometrial hyperplasia patients with the related risk factors, especially atypical endometrial hyperplasia.