Warburg and pasteur phenotypes modulate cancer behavior and therapy.

Energetic pathways combine in the heart of metabolism. These essential routes supply energy for biochemical processes through glycolysis and oxidative phosphorylation. Moreover, they support the synthesis of various biomolecules employed in growth and survival over branching pathways. Yet, cellular energetics are often misguided in cancers as a result of the mutations and altered signaling. As nontransformed and Pasteur-like cells metabolize glucose through oxidative respiration when only oxygen is sufficient, some cancer cells bypass this metabolic switch and run glycolysis at higher rates even in the presence of oxygen. The phenomenon is called aerobic glycolysis or the Warburg effect. An increasing number of studies indicate that both Warburg and Pasteur phenotypes are recognized in the cancer microenvironment and take vital roles in the regulation of drug resistance mechanisms such as redox homeostasis, apoptosis and autophagy. Therefore, the different phenotypes call for different therapeutic approaches. Combined therapies targeting energy metabolism grant new opportunities to overcome the challenges. Nevertheless, new biomarkers emerge to classify the energetic subtypes, thereby the cancer therapy, as our knowledge in coupling energy metabolism with cancer behavior grows.

Role of mesenchymal stem cell-derived soluble factors and folic acid in wound healing.

BACKGROUND: Mesenchymal stem cells (MSCs) are a type of adult stem cell consisting of a heterogeneous subset of stromal stem cells that can be isolated from adult tissues. Folic acid is another important contributor to tissue regeneration and repair, which affects the synthesis of some building block molecules used for wound healing. In this study, we examine the effect of folic acid and MSCderived soluble factors in the wound healing model. METHODS: Human umbilical vein endothelial cells (HUVECs) and bone marrow-derived MSCs (BMSCs) were cultured for this study. Cell proliferation analysis was done with xCELLigence RTCA. After 48 h of cultivation, the cell culture medium was collected as MSC conditional medium containing mesenchymal stem cell-derived soluble factors (MDFs). Different concentrations of MDFs (12%, 25%, 50%, 75%, and 100%) were applied to the HUVEC cell line. Folic acid (25, 30, 50, 60, 75, 90, and 100 µM) was tested by application of three different groups (control, 25 µM folic acid, 625 µM folic acid inhibitors) for proliferation on the HUVEC cell line. The combined effects of folic acid and MDFs were tested on the HUVEC cell line with 25 µM folic acid and 50 µM MDFs. All data were statistically analyzed using SPSS 15.0 for Windows. RESULTS: Significant differences were observed between controls and cells treated with folic acid, as well as between controls and both folic acid and MDFs (P < 0.05). Among the treated groups, the fastest wound closure rate was seen in cells treated with both folic acid and MDFs. DISCUSSION: The results show that both folic acid and MDFs increased the wound healing rate in HUVECs when they were used separately. The strongest benefits were seen in treatment using folic acid and MDFs together.

Role of mesenchymal stem cell-derived soluble factors and folic acid in wound healing

Background/aim: Mesenchymal stem cells (MSCs) are a type of adult stem cell consisting of a heterogeneous subset of stromal stem cells that can be isolated from adult tissues. Folic acid is another important contributor to tissue regeneration and repair, which affects the synthesis of some building block molecules used for wound healing. In this study, we examine the effect of folic acid and MSCderived soluble factors in the wound healing model. Materials and methods: Human umbilical vein endothelial cells (HUVECs) and bone marrow-derived MSCs (BMSCs) were cultured for this study. Cell proliferation analysis was done with xCELLigence RTCA. After 48 h of cultivation, the cell culture medium was collected as MSC conditional medium containing mesenchymal stem cell-derived soluble factors (MDFs). Different concentrations of MDFs (12%, 25%, 50%, 75%, and 100%) were applied to the HUVEC cell line. Folic acid (25, 30, 50, 60, 75, 90, and 100 µM) was tested by application of three different groups (control, 25 µM folic acid, 625 µM folic acid inhibitors) for proliferation on the HUVEC cell line. The combined effects of folic acid and MDFs were tested on the HUVEC cell line with 25 µM folic acid and 50 µM MDFs. All data were statistically analyzed using SPSS 15.0 for Windows. Results: Significant differences were observed between controls and cells treated with folic acid, as well as between controls and both folic acid and MDFs (P < 0.05). Among the treated groups, the fastest wound closure rate was seen in cells treated with both folic acid and MDFs. Conclusion: The results show that both folic acid and MDFs increased the wound healing rate in HUVECs when they were used separately. The strongest benefits were seen in treatment using folic acid and MDFs together.

Enteric Duplication Cysts in Children: A Single-Institution Series with Forty Patients in Twenty-Six Years.

PURPOSE: The purpose of the study was to evaluate our experience with enteric duplication cysts in 40 children during the past 26 years, while assessing the variability of their presentations and to propose an algorithm for surgical management. METHODS: We retrospectively analysed sex, age, clinical presentations, duplication site, surgical treatment, presence of ectopic tissue, complications, associated anomalies, and prognosis of 40 patients with gastrointestinal tract duplications who were surgically treated in our clinic. RESULTS: Overall, there was a predominance of boys (28 males, 70 %; 12 females, 30 %). The presenting symptom was vomiting in 23 patients, rectal bleeding in 11 patients, abdominal mass in 10 patients, abdominal pain in 9 patients, constipation in 6 patients, cough in 2 patients, and respiratory distress in 2 patients. In 30 patients, a complete excision of the cyst with additional segmental intestinal resection and anastomosis was performed. Cystectomy was performed in seven patients, while complete excision of the cyst with additional wedge resection was performed in two. A Wrenn procedure (mucosectomy) was performed in one patient. CONCLUSION: Due to the variability in the site of enteric duplications, a wide range of presenting symptoms can exist, which is challenging for diagnosis. In children with a diagnosis of acute abdomen, enteric duplication cysts should be considered, and these children should be further investigated for additional skeletal, urogenital, and gastrointestinal system pathologies. Surgical treatment depends on the site and type of the cyst.

Acousto-holographic reconstruction of whole-cell stiffness maps.

Accurate assessment of cell stiffness distribution is essential due to the critical role of cell mechanobiology in regulation of vital cellular processes like proliferation, adhesion, migration, and motility. Stiffness provides critical information in understanding onset and progress of various diseases, including metastasis and differentiation of cancer. Atomic force microscopy and optical trapping set the gold standard in stiffness measurements. However, their widespread use has been hampered with long processing times, unreliable contact point determination, physical damage to cells, and unsuitability for multiple cell analysis. Here, we demonstrate a simple, fast, label-free, and high-resolution technique using acoustic stimulation and holographic imaging to reconstruct stiffness maps of single cells. We used this acousto-holographic method to determine stiffness maps of HCT116 and CTC-mimicking HCT116 cells and differentiate between them. Our system would enable widespread use of whole-cell stiffness measurements in clinical and research settings for cancer studies, disease modeling, drug testing, and diagnostics.

The Effects of Bladder Diverticulum on the Pathophysiology of Bladder Outlet Obstruction: An Experimental Study in Guinea Pigs.

Objectives: This study is the first to urodynamically and histopathologically evaluates the effects of bladder diverticulum (BD) secondary to bladder outlet obstruction (BOO). Methods: Guinea pigs (n=32) weighing 900-1,000 g were divided randomly into four groups: Sham, BD, BOO, and BD combined with BOO. All guinea pigs in the four groups underwent urodynamic evaluation preoperatively and at 1 month postoperatively. The bladders were removed and examined histopathologically. Results: The post-operative filling detrusor pressure was lower in the Sham group (7.1±1.6 cm H2O) than in the BD (21.4±5.6 cm H2O) and BD with BOO groups (23.6±9.3 cm H2O) (p<0.05). There was no difference between the Sham and BOO (9.5±4.0) groups. Post-operative bladder compliance was better in the Sham group (2.3±0.8 ml/cm H2O) than in the BD (0.9±0.22 ml/cm H2O) and BD with BOO groups (0.6±0.3 ml/cm H2O) (p<0.05). Involuntary detrusor contraction was not observed in the Sham or BOO groups, but was observed in 37.5% of subjects in the BD and BD with BOO groups. On histological examination, the bladder wall was thicker (3.75±0.68 mm) (p=0.601), and the connective tissue volume was significant increased (p=0.046), in the bladder muscularis mucosa in the BD groups compared to the BOO group. Conclusion: Physiological and histopathological changes in the bladder with BD combined with BOO are more evident than with BOO alone.