Matrix metalloproteinases (MMPs) 2 are a large family of highly conserved metalloendopeptidases with proteolytic activity directed against a variety of extracellular matrix (ECM) substrates (1-3). MMPs have been implicated in basement membrane proteolysis, activation of growth factors, and cleavage of cell-adhesion molecules. Extending mechanistic investigation to cancer biology, numerous studies have shown that MMP overexpression enhances the invasive activity of tumor cell lines (4 -6). Analysis of human disease further supports the pro-tumorigenic role of MMPs, as increased expression of these proteases in tumor samples is clinically associated with invasion, metastasis, poor prognosis, and shorter survival times (7,8). In the specific case of squamous cell carcinoma (SCC), increased expression of membrane type 1-MMP (MT1-MMP, MMP14) is associated with ECM breakdown, tissue invasion, and lymph node metastasis (8).However, several animal studies have now clearly demonstrated that multiple members of the MMP family provide a paradoxically protective effect during the relentless molecular destruction that characterizes malignant progression. MMPs may have been initially identified as potent pro-tumorigenic proteases, but their simultaneous ability to function in an opposing, anti-tumorigenic role is now equally well established (9, 10). Such data underscore both the complexity of MMP activity in cellular signaling events as well as the importance of stringently evaluating the context in which these proteases take on either an anti-tumorigenic or pro-tumorigenic role. Intriguingly, several recent studies using SCC models have begun to suggest a putative mechanism through which MMPs may be induced to function primarily as anti-tumorigenic proteases. When exposed to carcinogens, MMP3-null mice developed squamous cell skin cancers that not only grew faster but were also strikingly less differentiated than those of control animals (11). Significantly, orthotopic injection of MMP3-expressing tumor cells resulted in pronounced tumor cell differentiation (12). However, although such findings indicate that MMPs may inhibit SCC progression by promoting tumor cell differentiation, the precise mechanism through which these proteinases regulate this process has not yet been elucidated.In normal tissue keratinocyte differentiation is a complex process mediated by cell-ECM and cell-cell interactions that subsequently activate downstream signaling pathways (13-15). Specifically, among structural proteins, integrins mediate primarily cell-ECM interactions, whereas cadherins are responsible for cell-cell interactions (13). In vitro activation of integrins or inhibition of cadherins after ligation or dominant negative expression, respectively, results in negative regulation of human keratinocyte differentiation (16 -18). Furthermore, beyond structural proteins, Rho GTPases are also known to be an important component of keratinocyte differentiation pathways. Rho signaling has been shown to mediate cell-cell and cell-matrix adhesion...

Pancreatic cancer is one of the deadliest of cancers with a dismal 5-year survival rate. Epidemiological studies have identified chronic pancreatitis as a risk factor for pancreatic cancer. Pancreatic cancer cells also demonstrate increased expression of the transcription factor Snail, a key regulator of epithelial-mesenchymal transition. As ethanol is one of the major causes of pancreatitis, we examined the effect of ethanol on Snail family members in immortalized human pancreatic ductal epithelial (HPDE) cells and in pancreatic cancer cells. Ethanol induced Snail mRNA levels 2.5-fold in HPDE cells, with only 1.5-fold mRNA induction of the Snail-related protein Slug. In contrast, ethanol increased Slug mRNA levels 1.5-2-fold in pancreatic cancer cells, with minimal effect on Snail. Because Snail increases invasion of cancer cells, we examined the effect of ethanol on invasion of HPDE and pancreatic cancer cells. Surprisingly, ethanol decreased invasion of HPDE cells, but had no effect on invasion of pancreatic cancer cells. Mechanistically, ethanol increased adhesion of HPDE cells to collagen and increased expression of the collagen binding α2- and β1-integrins. In contrast, ethanol did not affect collagen adhesion or integrin expression in pancreatic cancer cells. Also in contrast to HPDE cells, ethanol did not attenuate ERK1/2 phosphorylation in pancreatic cancer cells; however, inhibiting ERK1/2 decreased pancreatic cancer cell invasion. Overall, our results identify the differential effects of ethanol on premalignant and malignant pancreatic cells, and demonstrate the pleiotropic effects of ethanol on pancreatic cancer progression.

The outbreak of the new coronavirus (COVID19), has caused devastating effects and was declared as a major pandemic by the World Health Organization (WHO). Apart from knowing the main causes, it's very important to timely diagnose the virus in an individual, so that treatment and isolation (if needed) can start as early as possible and spread of the virus is contained among the healthy people. In this research, we discuss various machine learning (ML) and deep learning (DL) approaches that have been proposed for the diagnosis of the virus using different bio-indicators with particular focus on lungs imaging. A detailed analysis of existing techniques is presented with future perspective on the use of new machine learning techniques for the diagnosis of the COVID19 and other similar viruses.

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There is still much we do not know about the impact of COVID-19 on the health of pregnant and postpartum women and pregnancy outcomes. Current evidence suggests that there is biological plausibility for worse outcomes among this population. This case report details the clinical care given to a postpartum Hispanic and obese woman diagnosed with COVID-19 in April 2020. We report the care she and her newborn received and her progression through the virus. We discuss the current knowledge surrounding COVID-19 among pregnant and postpartum women. While research supports COVID-19 outcomes being comparable to the general population, there is limited research in this area. Clinical trials, acting on the side of caution, have tended to exclude pregnant women from participation. Therefore, there is a need for further research that can inform evidence-based policy decisions related to COVID-19 in pregnant and postpartum women.