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Background: Stem cell differentiation therapy is a promising strategy in cancer treatment. we show that protein cocktail prepared from serum starved fibroblasts has therapeutic potential based on this strategy. Methods: The condition medium was prepared from foreskin isolated fibroblasts and analyzed by Liquid chromatography electrospray ionization mass spectrometry-mass spectrometry (LC-ESI-MS/MS). LA7 mammary gland cancer stem cells originated tumors were induced in Sprague Dawley rats. The rats treated subcutaneously with DMEM (group A), condition medium (group B), or normal saline (group C) once daily for 7 days. Then the tumors were removed and divided into the two parts, one part was used to quantify gene expression by stem-loop RT-qPCR assay and the other part was used for Hematoxylin & Eosin (H & E), Giemsa, and immunohistochemistry (IHC) staining. Results: All induced tumors appeared as sarcomatoid carcinoma (SC). Immunohistochemistry staining confirmed this conclusion by recognizing the tumor as Ki67 + , cytokeratin + , vimentine + , and estrogen receptor negative SC. RT-qPCR analysis revealed that Oct4-, Sox-2, Nanog-gene expression was much reduced in the condition medium treated tumors versus proper controls (p< 0.05). Tissue necrosis was more prevalent in this group while tumors volume was diminished almost by 40%. The LC-ESI-MS/MS analysis unrevealed the stemness reducing and the cell death inducing proteins such as, pigment epithelium-derived factor (PEDF), insulin like growth factor binding protein-5 (IGFBP-5) and -7 (IGFBP-7) in the condition medium. Conclusions: This study showed that the substances released from starved human fibroblasts were able to down-regulate the stemness-related genes and induce necrosis in LA7 derived tumors.

Management of acute gastroenteritis (AGE) includes treatment of underlying infections as well, since AGE may be an atypical presentation of urinary tract infection (UTI). The present study was planned to study the prevalence of UTI in children presenting with AGE. Two hundred consecutive patients presenting with AGE at 2 months to 4 years of age to one center's emergency department over 1 year were evaluated for UTI. Of 200 patients, 103 were male and 97 were female. One patient had infectious diarrhea. One hundred and forty-one (70.5%) patients were febrile, 63 (31.5%) patients had mild dehydration, 107 (53.5%) patients had moderate dehydration and 30 (15%) patients had severe dehydration. Twenty-five (12.5%) patients had pyuria. Fifteen (7.5%) patients had positive urine cultures. One of these (6.7%) patients had a history of UTI in the mother and 5 (33.3%) patients reported a history of UTI in their siblings. Of 15 patients with UTI, 13 (86.6%) were girls; 5 (38.4%) had labial adhesions. Escherichia coli and Klebsiella were isolated in 4 and one cases in urine culture, respectively. UTI underlies 7.5% of children presenting with AGE.

This study aimed to investigate the protective effects of 16h-serum starved-fibroblasts culture supernatant (16h-SFS) with and without bone marrow-derived mesenchymal stem/stromal cells (BMSCs) on the pathological and immunomolecular features of LA7 cancer stem cells-induced mammary tumor in rats. In an interventional study, 30 female rats were selected and the breast tumors were induced in all rats by LA7 cell and then were divided into six groups. The rats receiving the DMEM or PBS were considered as control groups. Three other groups received 16h-SFS solution, BMSCs, and 16h-SFS + BMSCs, respectively. After the treatment procedure, the tumor size were measured. Then the tumor tissues were evaluated in 10 high-power fields regarding the angiogenesis rate, mitotic cells, and type of immune cells infiltrated into the tumor microenvironment. Also, the expression of Cxcl9, Cxcl10, and Cxcl12 chemokines in tumors was examined by the Real-Time PCR method. Tumor size in 16h-SFS, BMSCs, and 16h-SFS + BMSCs groups were significantly reduced. Also, the tumor angiogenesis was significantly decreased in 16h-SFS + BMSCs vs. DMEM group. Also, the highest presence of mononuclear immune cells was observed in tumor tissues of the 16h-SFS + BMSCs group. A significant increase in Cxcl9 gene expression was observed in 16h-SFS + BMSCs vs. PBS and DMEM groups. Also, the Cxcl10 gene expression 16h-SFS + BMSCs group significantly increased vs. 16h-SFS, BMSCs, PBS, and DMEM groups. Our findings suggest that simultaneous administration of 16h-SFS and BMSC has an anti-tumor effect against LA7-induced tumors by modulating pathological and immeunological features. Therefore, these compounds could be considered as a promising cancer therapeutic approach.

Background: Immunometabolism targeting therapy of auto-inflammatory diseases is an emerging strategy compared to immune system global suppression. However, our knowledge in this field needs promotion. Objectives: We examined the effects of serum starvation stress on metabolic activity in human peripheral blood mononuclear cells (PBMCs). Methods: Fresh immune cells were isolated from four healthy adult volunteers and cultivated with or without fetal bovine serum (FBS) at various time points under standard conditions. Glucose and intra- and extracellular lactate levels were assessed using routine techniques, and 3-(4, 5 -dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) reduction assay was used to determine mitochondrial function. Results: Spindle shape macrophage-like cells, which appeared early, were replaced at 96 h by large round monocytes/macrophage-like cells, with more frequency in the non-starved group. Interestingly, serum starvation dictated a status, especially in monocyte/macrophage-like cells, that led to prolong decrement in mitochondrial dehydrogenase-mediated reduction of MTT. This difference was confirmed with the MTT assay quantitatively (P < 0.05). Moreover, the intra- and extracellular lactate concentrations were lower in starved cells than in non-starved controls (P < 0.05), and glucose levels were higher in 72 h starved cell culture supernatants than in non-starved control cells (P < 0.05). Conclusions: This study showed that under serum starvation-induced metabolic stress, lactate production is altered in immune cells, and total oxidative mitochondrial activity is reduced in macrophage-like cells. These findings open a new window to target immune cell metabolism for the treatment of autoinflammatory and autoimmune diseases.