The Transcription Factor GLI1 Mediates TGFb1 Driven EMT in Hepatocellular Carcinoma via a SNAI1-Dependent Mechanism

The role of the epithelial-to-mesenchymal transition (EMT) during hepatocellular carcinoma (HCC) progression is well established, however the regulatory mechanisms modulating this phenomenon remain unclear. Here, we demonstrate that transcription factor glioma-associated oncogene 1 (GLI1) modulates EMT through direct up-regulation of SNAI1 and serves as a downstream effector of the transforming growth factor-b1 (TGFb1) pathway, a well-known regulator of EMT in cancer cells. Overexpression of GLI1 increased proliferation, viability, migration, invasion, and colony formation by HCC cells. Conversely, GLI1 knockdown led to a decrease in all the above-mentioned cancer-associated phenotypes in HCC cells. Further analysis of GLI1 regulated cellular functions showed that this transcription factor is able to induce EMT and identified SNAI1 as a transcriptional target of GLI1 mediating this cellular effect in HCC cells. Moreover, we demonstrated that an intact GLI1-SNAI1 axis is required by TGFb1 to induce EMT in these cells. Together, these findings define a novel cellular mechanism regulated by GLI1, which controls the growth and EMT phenotype in HCC.National Institutes of Health Grants CA100882 and CA128633 (to LRR) and CA165076; the Mayo Clinic Center for Cell Signaling in Gastroenterology (NIDDK P30DK084567) (to MEFZ); the Mayo Clinic Cancer Center (CA15083), the Mayo Clinic Center for Translational Science Activities (NIH/NCRR CTSA Grant Number KL2 RR024151), and an American Gastroenterological Association Foundation for Digestive Health and Nutrition Bridging Grant (to LRR)

The role of individual and community factors on institutional delivery in Somaliland: a study based on the 2020 Somaliland demographic health survey

BackgroundMaternal mortality remains a critical concern in low-income countries, where low utilization of institutional delivery services is a contributing factor. This study investigates the influence of individual and community-level factors on institutional delivery among women in Somaliland, a region with a high maternal mortality rate.MethodsThis cross-sectional study used data from the 2020 Somaliland Demographic and Health Survey (SDHS), a nationally representative survey of 3804 women aged 15–49. We employed descriptive statistics and Chi-square tests to examine bivariate associations and multi-level binary logistic regression to assess the impact of individual and community-level factors on the place of delivery.ResultsOnly 30.8% of deliveries occurred in health institutions. Bivariate analyses showed significant associations between institutional delivery and maternal age, education (χ² = 328.534, p < 0.001), husband's education (χ² = 362.669, p < 0.001), wealth (χ² = 787.937, p < 0.001), region (χ² = 50.760, p < 0.001), and parity (χ² = 65.227, p < 0.001). Multilevel analysis revealed that 50% of the variance in place of delivery was attributable to community level factors (Model I). Higher maternal education was significantly associated with increased odds of institutional delivery (AOR = 8.87, p < 0.05), while nomadic residence (AOR = 0.28, p < 0.05), residing in Sanaag region (AOR = 0.36, p < 0.05), high parity (five or more children) (AOR = 0.52, p < 0.05), not intending to use contraceptives (AOR = 0.62, p < 0.05), and wanting the pregnancy later (AOR = 0.79, p < 0.05) were significantly associated with decreased odds of institutional delivery. Women in the highest wealth quintile were significantly more likely to deliver in a health facility (AOR = 18.71, p < 0.05).ConclusionThe study highlights the complex interplay of individual and community-level factors influencing the utilization of institutional delivery in Somaliland. Interventions to promote health facility deliveries must address socioeconomic disparities, improve women's education, ensure accessibility of healthcare for nomadic communities, reduce regional variations, promote family planning and reproductive health services, and take into consideration the impact of parity on health seeking behaviors

SINE elements of Entamoeba dispar.

Entamoeba histolytica and E. dispar are closely related protozoan parasites; the former causes clinical amoebiasis in humans while the latter appears to be non-pathogenic. The molecular biology of E. histolytica shows a number of unusual features, one of which is the abundance of polyadenylated but apparently untranslatable mRNAs produced; many of these are the product of at least three families of SINEs (EhSINE1-3). Here we show that the genome of E. dispar contains numerous copies of a SINE element (EdSINE1) whose 5'- and 3'-ends are very similar to those of EhSINE1 but with a much less similar middle portion. Twelve out of 18 copies examined had target site duplications. In none out of six cases examined was there a SINE element in the homologous region of the E. histolytica genome but a single copy of EdSINE1 is present in E. histolytica where it is identified as EhSINE3

Testicular Diffuse Large B-Cell Lymphoma of Activated B-Cel Subtype Is Frequently Associated with Clonally Related Non-Follicular Small B-Cell Lymphoma in the Bone Marrow.

Abstract Diffuse large B-cell lymphoma (DLBCL) of the testis is an uncommon non-Hodgkin’ s lymphoma. It accounts for 1 % of all lymphomas but represents the most frequent testicular tumor in men over the age of 60. Most patients have localized disease but involvement of other extranodal sites is not uncommon. Of interest, an activated B-cell like (ACT) phenotype has been reported in the majority of testicular DLBCL and even those cases with a germinal center B-cell (GC) phenotype seem by micro-array analysis to display an mRNA profile of activated B-cells (1). This contrasts with the incidence of this phenotype of DLBCL at most other locations. Whether the activated B-cell phenotype may explain the dismal outcome of DLBCL of the testis is an interesting hypothesis. As part of a retrospective study of all cases of testicular DLBCL in the lymphoma registry of the Norwegian Radium Hospital, diagnosed in the period between 1995 and 2005, we have carefully reviewed all pathology data. Nineteen patients with a diagnosis of testicular lymphoma were retrieved from the registry. The diagnoses were reviewed and immunohistochemical staining on tissue sections of testis tumors was performed in order to determine the prognostically different subgroups according to Hans et al (2). In addition, tissue sections of bone marrow biopsies or flowcytometric analyses of bone marrow aspirates, performed for staging purposes, were reviewed. Seven (36%) and 13 (65%) of the 19 testicular DLBCL were of the GC and ACT subtype, respectively. Quite unexpectedly, bone marrow involvement by a small B-cell proliferation was detected in 9/19 cases (47 %). None of the cases showed bone marrow involvement by DLBCL. Further typing of the small B-cell proliferations in the bone marrow, revealed 3 cases of lymphoplasmacytic lymphoma (LPL), 5 cases with the morphology and immunophenotype compatible with marginal zone B-cell lymphoma (MZL), and 1 case of chronic lymphocytic leukemia (CLL). None, but one of those cases of small B-cell lymphomas were diagnosed before diagnosis of the testicular DLBCL. Interestingly, 7/9 patients with a concurrent small B-cell proliferation in the bone marrow had the ACT subtype of testicular DLBCL, whereas 2 had a GC subtype DLBCL. In six cases appropriate diagnostic biopsies were available to investigate whether the testicular DLBCL and the bone marrow lymphoma were derived from the same B-cell clone by size-fractionation and/or sequencing of the respective rearranged immunoglobulin genes. Interestingly, in only one case of LPL in the bone marrow with GC testicular DLBCL, two different clones were detected, whereas in the other five cases the small B-cell proliferation in the bone marrow and the testicular DLBCL were derived from the same clone. In conclusion, testicular DLBCL of ACT subtype is often associated with clonally-related small B-cell proliferation in the bone marrow. It is of interest that none of the lymphomas in the bone marrow were follicular lymphomas. It seems therefore likely that many testicular DLBCL of ACT subtype may represent transformed non-follicular small B-cell lymphoma. This hypothesis needs corroboration by genetic data.</jats:p