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Background: Candida albicans is the important opportunistic fungal pathogens which can cause oral Candidiasis and even more seriously systemic infection. Apoptosis of C. albicans induced by environmental factor such as weak acid and antifungal drugs were studied recently. Illustrating the phenomenon of apoptosis in C. albicans may help us to discover new antifungal therapy by activating the fungal cells to suicide., Methods: Two oral C. albians clinical isolates which isolated respectively from healthy host [Strain 23C: minimal inhibition concentration (MIC) is 0.125 microg/ml for Amphotericin B (AmB)] and advanced cancer patient (Strain 28A: MIC is 2 microg/ml for AmB), were induced by 1 microg/ml AmB in vitro for 200 min, and then studied the apoptosis markers using terminal deoxynucletidyltransferase-mediated dUTP nick end labeling (TUNEL) (shown by diaminobenzidine and fluorescent isothiocyanate), and the ultrastructure of cell nuclear using transmission electron microscope (TEM), quantitative analysis using flow cytometry for the rapid exposure of phosphatidylserine at the outer membrane and propodium iodide (PI) double staining. C. albicans conference strain YEM30 was used as the control strain., Results: With TUNEL assay and TEM, we detected the typical characteristics of apoptosis. Strain 23C (with low MIC) showed significantly higher percentage of apoptosis (19.92%) compared with Strain 28A (with high MIC) which was isolated from the cancer patient (7.29%) (P < 0.01). In addition, 7.3% of early apoptosis cells of Strain 23C can form colonies on the plates, while 15% for Strain 28A. None of the PI+ cells can form colony., Conclusions: Apoptosis of oral C. albicans isolates can be induced by AmB. The feature of antifungal drug susceptibility of the oral C. albicans clinical isolates may associate with the response of apoptosis inducing.

Aims: Diabetic nephropathy (DN) is a leading cause of end‐stage renal disease. BASP1 (brain acid‐soluble protein) is up‐regulated in podocyte‐specific protein phosphatase 2A knockout mice (Pod‐PP2A‐KO) that develop kidney dysfunction. Here, we explore the role of BASP1 for podocytes in DN. Methods: BASP1 was assessed in kidneys from DN patients and DN mouse models, podocyte specific BASP1 knockout mice (Pod‐BASP1‐KO mice) were generated and studied in vivo. Furthermore, podocyte injury and apoptosis were measured after BASP1 knockdown and overexpression in a mouse podocyte cell line (MPC5). Potential signalling pathways involved in podocyte apoptosis were detected. Results: BASP1 expression was up‐regulated in DN patients compared to normal controls. BASP1 specific deletion in podocytes protected against podocyte injury by reducing the loss of expression of slit diaphragm molecules and foot process effacement in the DN model. BASP1 promoted actin cytoskeleton rearrangements and apoptosis in the MPC5 podocyte line. Molecules involved in the p53 pathway were down‐regulated in BASP1 knockdown podocytes treated with high glucose compared to controls. BASP1 promoted podocyte apoptosis and P53 pathway activation through co‐repression with Wilms' tumour 1 transcription factor (WT1). Conclusion: BASP1 activates the p53 pathway through modulation of WT1 to induce podocyte apoptosis in diabetic nephropathy. [ABSTRACT FROM AUTHOR]

Transforming growth factor ( TGFβ)3 is essential for palate development, particularly during the late phase of palatogenesis when the disintegration of the palatal medial edge seam ( MES) occurs resulting in mesenchymal confluence. The MES is composed of medial-edge epithelium ( MEE) of opposite palatal shelves; its complete disintegration is essential for mediating correct craniofacial morphogenesis. This phenomenon is initiated by TGFβ3 upon adherence of opposing palatal shelves, and subsequently epithelial-mesenchymal transition ( EMT) instigates the loss of E- Cadherin, causing the MES to break into small epithelial islands forming confluent palatal mesenchyme; however, apoptosis and cell migration or in combination of all are other established mechanisms of seam disintegration. To investigate the molecular mechanisms that cause this E- Cadherin loss, we isolated and cultured murine embryonic primary MES cells from adhered palates and employed several biological approaches to explore the mechanism by which TGFβ3 facilitates palatal seam disintegration. Here, we demonstrate that TGFβ3 signals by activating both Smad-dependent and Smad-independent pathways. However, activation of the two most common EMT related transcription factors, Snail and SIP, was facilitated by Smad-independent pathways, contrary to the commonly accepted Smad-dependent pathway. Finally, we provide the first evidence that TGFβ3-activated Snail and SIP1, combined with Smad4, bind to the E- Cadherin promoter to repress its transcription in response to TGFβ3 signaling. These results suggest that TGFβ3 uses multiple pathways to activate Snail and SIP1 and these transcription factors repress the cell-cell adhesion protein, E- Cadherin, to induce palatal epithelial seam EMT. Manipulation and intervention of the pathways stimulated by TGFβ3 during palate development may have a significant therapeutic potential. [ABSTRACT FROM AUTHOR]