Downregulation of Bit1 expression promotes growth, anoikis resistance, and transformation of immortalized human bronchial epithelial cells via Erk activation-dependent suppression of E-cadherin.

The mitochondrial Bit1 protein exerts tumor-suppressive function in NSCLC through induction of anoikis and inhibition of EMT. Having this dual tumor suppressive effect, its downregulation in the established human lung adenocarcinoma A549 cell line resulted in potentiation of tumorigenicity and metastasis in vivo. However, the exact role of Bit1 in regulating malignant growth and transformation of human lung epithelial cells, which are origin of most forms of human lung cancers, has not been examined. To this end, we have downregulated the endogenous Bit1 expression in the immortalized non-tumorigenic human bronchial epithelial BEAS-2B cells. Knockdown of Bit1 enhanced the growth and anoikis insensitivity of BEAS-2B cells. In line with their acquired anoikis resistance, the Bit1 knockdown BEAS-2B cells exhibited enhanced anchorage-independent growth in vitro but failed to form tumors in vivo. The loss of Bit1-induced transformed phenotypes was in part attributable to the repression of E-cadherin expression since forced exogenous E-cadherin expression attenuated the malignant phenotypes of the Bit1 knockdown cells. Importantly, we show that the loss of Bit1 expression in BEAS-2B cells resulted in increased Erk activation, which functions upstream to promote TLE1-mediated transcriptional repression of E-cadherin. These collective findings indicate that loss of Bit1 expression contributes to the acquisition of malignant phenotype of human lung epithelial cells via Erk activation-induced suppression of E-cadherin expression.

Case Report of Myroides odoratimimus Cellulitis in Chronic Venous Stasis Dermatitis With Literature Review.

Myroides spp.-induced cutaneous infections are rare, with only 17 reported cases in the literature. Myroides spp. behave like low-grade opportunistic pathogens, with symptomatic infections observed typically in severely immunocompromised patients and seldom in immunocompetent patients. In this paper, we present an immunocompetent 61-year old male with a past medical history of hypertension, hyperlipidemia, morbid obesity, and patient-reported peripheral neuropathy who presented to the transitional care clinic with bilateral lower extremity swelling and hemosiderin-pigmented dry wounds consistent with diagnosis of chronic venous stasis dermatitis with resolved secondary Myroides odoratimimus infection. Further literature review about Myroides spp. and its resistance mechanism, antibiotic susceptibility, and biofilm production are also included in this paper.

NMR analysis and molecular dynamics conformation of α-1,6-linear and α-1,3-branched isomaltose oligomers as mimetics of α-1,6-linked dextran.

The conformational preferences of several α-1,6-linear and α-1,3-branched isomalto-oligosaccharides were investigated by NMR and MD-simulations. Right-handed helical structure contributed to the solution geometry in isomaltotriose and isomaltotetraose with one nearly complete helix turn and stabilizing intramolecular hydrogen bonds in the latter by MD-simulation. Decreased helix contribution was observed in α-1,3-glucopyranosyl- and α-1,3-isomaltosyl-branched saccharide chains. Especially the latter modification was predicted to cause a more compact structure consistent with literature rheology measurements as well as with published dextranase-resistant α-1,3-branched oligosaccharides. The findings presented here are significant because they shed further light on the conformational preference of isomalto-oligosaccharides and provide possible help for the design of dextran-based drug delivery systems or for the targeted degradation of capsular polysaccharides by dextranases in multi-drug resistant bacteria.