In the long term, diabetes profoundly affects multiple organs, such as the kidney, heart, brain, liver, and eyes. The gradual loss of function in these vital organs contributes to mortality. Nonetheless, the effects of diabetes on the lung tissue are not well understood. Clinical and experimental data from our studies revealed that diabetes induces inflammatory and fibrotic changes in the lung. These changes were mediated by TGF-β-activated epithelial-to-mesenchymal transition (EMT) signaling pathways. Our studies also found that glucose restriction promoted mesenchymal-to-epithelial transition (MET) and substantially reversed inflammatory and fibrotic changes, suggesting that diabetes-induced EMT was mediated in part by the effects of hyperglycemia. Additionally, the persistent exposure of diabetic cells to high glucose concentrations (25 mM) promoted the upregulation of caveolin-1, N-cadherin, SIRT3, SIRT7 and lactate levels, suggesting that long-term diabetes may promote cell proliferation. Taken together, our results demonstrate for the first time that diabetes induces fibrotic changes in the lung via TGF-β1-activated EMT pathways and that elevated SMAD7 partially protects the lung during the initial stages of diabetes. These findings have implications for the management of patients with diabetes.

Cyclin-dependent kinases (cdks) are central catalytic units of cell division cycle. Among the cdk family members, cdk1 has critical roles in multiple phases of the cell cycle. Aberrant expression or hyper-actions of cdk1 are tumorigenic and yet the complex oncogenic network that regulates its turnover is poorly understood. We found a hitherto unexplored functional connection between skp2 and cdk1 turn over. In vitro knockdown or overexpression of skp2 in cultured cells reduced or induced cdk1 expression indicating skp2 as a positive driver for cdk1. A partial inhibitory role for p27 was identified in this context. Interestingly, concurrent overexpression of skp2 and p27 favored cdk1 upregulation in vitro, which correlated well with similar observations in clinical tumor samples. We found that the transcription factor FOXM1 may play a central role in the skp2-cdk1 loop. Additional molecular involvement in the skp2-cdk1 loop was also explored. In conclusion, our results revealed hitherto unexplored p27 independent molecular mechanisms for skp2 driven tumor progression. Our results support the previous findings that skp2 may be a potential therapeutic target for the management of tumors. J. Cell. Biochem. 118: 797-807, 2017. © 2016 Wiley Periodicals, Inc.

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Introduction: Spindle cell tumors constitute an important component of soft tissue tumors. Fine needle aspiration cytology provides a predictive diagnosis of type and nature of these neoplasms. Methods: This study was conducted for a period of four years. Results: A total of 124 cases were diagnosed as soft tissue spindle cell tumors cytologically. Of these, 86 (69.35%) cases were benign and 38 (30.64%) were malignant tumors. 52 cases were available for histopathological follow up of which 49 cases (94.23%) showed positive correlation. Though there are no specific tissue architectural patterns in cytological smears, they are helpful in providing predictive diagnosis of benign or malignant nature of the tumour and in many cases also of specific tumor type. However, histopathology is considered as "gold standard" in diagnosing spindle cell tumors. Ancillary techniques are helpful in providing definitive diagnosis thus increasing the diagnostic accuracy of FNAC. There were 2 false negative cases which were cytologically diagnosed as Schwannoma and Neurofibroma because of the presence of wavy spindle cells and blood but both cases were diagnosed as malignant peripheral nerve sheath tumor on histopathology. There was 1 false positive case cytologically diagnosed as malignant spindle cell tumor but histopathologically diagnosed as Pleomorphic lipoma. Conclusion: Cytological and histopathological correlation was available in 36 benign tumors and 16 malignant tumors. Among benign tumors, 94.44% (34 cases) showed positive correlation, 5.56% (2 cases) showed negative correlation. Whereas among malignant tumors, 93.75% (15 cases) showed positive correlation and 6.25% (1 case) showed negative correlation between cytologic and histopathologic diagnosis.

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