Claudin-4 is part of the Claudin family of transmembrane tight junction (TJ) proteins found in almost all tissues and, together with adherens junctions and desmosomes, forms epithelial and endothelial junctional complexes. Although the distribution of Claudin-4 occurs in many cell types, the level of expression is cell-specific. Claudin proteins regulate cell proliferation and differentiation by binding cell-signaling ligands, and its expression is upregulated in several cancers. As a result, alterations in Claudin expression patterns or distribution are vital in the pathology of cancer. Profiling the genetic expression of Claudin-4 showed that Claudin-4 is also a receptor for the clostridium perfringens enterotoxin (CPE) and that Claudin-4 has a high sequence similarity with CPE’s high-affinity receptor. CPE is cytolytic due to its ability to form pores in cellular membranes, and CPE treatment in breast cancer cells have shown promising results due to the high expression of Claudin-4. The C-terminal fragment of CPE (c-CPE) provides a less toxic alternative for drug delivery into breast cancer cells, particularly metastatic tumors in the brain, especially as Claudin-4 expression in the central nervous system (CNS) is low. Therefore, c-CPE provides a unique avenue for the treatment of breast–brain metastatic tumors.
Trypanosoma cruzi (T. cruzi), the causative agent of Chagas disease, has infected 6 million people, putting 70 million people at risk worldwide. Presently, very limited drugs are available, and these have severe side effects. Hence, there is an urgency to delve into other pathways and targets for novel drugs. Trypanosoma cruzi (T. cruzi) expresses a number of different cyclic AMP (cAMP)-specific phosphodiesterases (PDEs). cAMP is one of the key regulators of mammalian cell proliferation and differentiation, and it also plays an important role in T. cruzi growth. Very few studies have demonstrated the important role of cyclic nucleotide-specific PDEs in T. cruzi’s survival. T. cruzi phosphodiesterase C (TcrPDEC) has been proposed as a potential new drug target for treating Chagas disease. In the current study, we screen several analogs of xanthine for potency against trypomastigote and amastigote growth in vitro using three different strains of T. cruzi (Tulahuen, Y and CA-1/CL72). One of the potent analogs, GVK14, has been shown to inhibit all three strains of amastigotes in host cells as well as axenic cultures. In conclusion, xanthine analogs that inhibit T. cruzi PDE may provide novel alternative therapeutic options for Chagas disease.
COVID-19 is a viral infection that resulted in a global pandemic. In the United States, COVID-19 caused incommensurate deaths, especially among members of minority groups. Previous literature shows comorbidities such as hypertension (HTN), diabetes mellitus (DM) and obesity (OBS) have been implicated in the severity of COVID-19 cases regardless of racial or ethnic group classification. However, minority populations, particularly people of African descent experienced higher mortality as they carry a disproportionately heavier burden in comorbidities cases. In this study we first confirm current literature on COVID-19 incidence and its correlation with the prevalence of comorbidities in various racial and ethnic populations, using anonymous and aggregated data from the Nashville General Hospital at Meharry, an Institute for the Study of Minority Health. We also evaluated the prevalence of comorbidities in minority patients and computed the correlation between the COVID-19 incidence and a permuted prevalence of comorbidities. A total of 959 patients were reviewed and our study indicates COVID-19 patients classified as Non-Hispanic Blacks (NHB) were approximately 3 times more likely to have an HTN or DM or both HTN and DM diagnosis. The chances double to be approximately six times higher when an OBS diagnosis is included singularly or in conjunction with either HTN or DM or both HTN and DM.
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