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The functional diversity of β-dystroglycan is attributable to its dual distribution, the plasma membrane, and the nucleus. In the plasma membrane, β-DG is a component of the dystrophin-associated protein complex. In the nucleus, β-DG assembles with the nuclear lamina and emerin. Recent findings indicate a role for β-DG in senescence, as its knockout in C2C12 myoblasts induces genomic instability and promotes the senescent state. This study analyzed the behavior of β-DG in three distinct models of senescence: chronologically aged fibroblasts, sodium butyrate (NaBu)-induced senescent fibroblasts, and fibroblasts from a Hutchinson–Gilford progeria syndrome (HGPS) patient. β-DG was found mainly in the nucleus in all the senescent cell types, with a certain mislocalization to the cytoplasm in HGPS and NaBu-treated fibroblasts. Furthermore, the full-length β-DG (43 kDa) and the cleaved intracellular domain (ICD; ~26 kDa) were identified. The ICD level increased in aged fibroblasts, but its yield was poor or virtually nonexistent in NaBU-induced and HGPS fibroblasts, respectively. Remarkably, β-DG was sequestered by progerin in HGPS cells, hindering its interaction with lamin A. In summary, the observed alterations in β-DG may be associated with the senescent state, and such findings will serve for future studies aimed at elucidating its role in senescence.

Hutchinson‐Gilford progeria syndrome (HGPS) is a premature aging disease caused by progerin, a mutant variant of lamin A. Progerin anchors aberrantly to the nuclear envelope disrupting a plethora of cellular processes, which in turn elicits senescence. We previously showed that the chromosomal region maintenance 1 (CRM1)‐driven nuclear export pathway is abnormally enhanced in patient‐derived fibroblasts, due to overexpression of CRM1. Interestingly, pharmacological inhibition of CRM1 using leptomycin B rescues the senescent phenotype of HGPS fibroblasts, delineating CRM1 as a potential therapeutic target against HGPS. As a proof of concept, we analyzed the beneficial effects of pharmacologically modulating CRM1 in dermal fibroblasts from HGPS patients and the LMNAG609G/G609G mouse, using the first‐in‐class selective inhibitor of CRM1 termed selinexor. Remarkably, treatment of HGPS fibroblasts with selinexor mitigated senescence and promoted progerin clearance via autophagy, while at the transcriptional level restored the expression of numerous differentially‐expressed genes and rescued cellular processes linked to aging. In vivo, oral administration of selinexor to the progeric mouse resulted in decreased progerin immunostaining in the liver and aorta, decreased progerin levels in most liver, lung and kidney samples analyzed by immunoblotting, and improved aortic histopathology. Collectively our data indicate that selinexor exerts its geroprotective action by at least two mechanisms: normalizing the nucleocytoplasmic partition of proteins with a downstream effect on the aging‐associated transcriptome and decreasing progerin levels. Further investigation of the overall effect of selinexor on LmnaG609G/G609G mouse physiology, with emphasis in cardiovascular function is warranted, to determine its therapeutic utility for HGPS and aging‐associated disorders characterized by CRM1 overactivity. Pharmacological inhibition of CRM1 mediated by selinexor, the first‐in‐class selective inhibitor of CRM1, mitigates the senescent phenotype of Hutchinson‐Gilford progeria syndrome (HGPS) patients‐derived primary fibroblasts. Treatment of HGPS fibroblasts with selinexor promotes the clearances of progerin via autophagy activation, restores the expression of numerous differentially expressed genes, and rescues various aging‐linked cellular processes. Oral administration of selinexor to the LmnaG609G/G609G progeric mouse decreased progerin immunostaining in the liver and aorta and improved aortic histopathology.

Colorectal cancer (CRC) is one of the leading types of cancer worldwide. CRC development has been associated with the constitutive activation of signal transducer and activator of transcription 3 (STAT3). STAT3 is a master regulator of inflammation during cancer-associated colitis, and becomes upregulated in CRC. In CRC, STAT3 is activated by IL-6, among other pro-inflammatory cytokines, inducing the expression of target genes that stimulate proliferation, angiogenesis and the inhibition of apoptosis. One of the main STAT3-regulated inhibitors of apoptosis is survivin, which is a bifunctional protein that regulates apoptosis and participates in cell mitosis. Survivin expression is normally limited to foetal tissue; however, survivin is also upregulated in tumours. In silico and experimental analyses have shown that the STAT3 interactome is relevant during CRC progression, and the constitutive STAT3-survivin axis participates in development of the tumour microenvironment and response to therapy. The presence of a STAT3-survivin axis has been documented in CRC cohorts, and the expression of these molecules is associated with poor prognosis and a higher mortality rate in patients with CRC. Thus, STAT3, survivin, and the upstream activators IL-6 and IL-6 receptor, are considered therapeutic targets for CRC. Efforts to develop drugs targeting the STAT3-survivin axis include the evaluation of phytochemical compounds, small molecules and monoclonal antibodies. In the present review, the expression, function and participation of the STAT3-survivin axis in the progression of CRC were investigated. In addition, an update on the pre-clinical and clinical trials evaluating potential treatments targeting the STAT3-survivin axis is presented.

Background: Although legume protein extracts are useful in food preparation and processing as foam stabilizers and as viscosity, palatability and nutrition enhancers, many legume proteins from South America have not been characterized extensively. One such legume is the ñuña bean (Phaseolus vulgaris L.), which is cooked using dry heat until the cotyledons rapidly expand with a pop. The bean is widely cultivated in the Andes, but almost unknown elsewhere. Objective & Methods: In this study, we characterized ten functional properties of a ñuña protein extract using standard food analysis methods. Results: The extract was similar to other legume protein extracts for many properties (amino acid profile, proximate analysis, yield, water absorption, color, isoelectric point, and thermogravimetric analysis). The electrophoretic analysis revealed that the sample was nearly pure phaseolin. Additionally, the ability to form foam and increase solution viscosity were comparatively low when contrasted to other extracts. Conclusion: These properties make ñuña protein extract useful as a nearly pure phaseolin nutrition enhancer in beverages where foaming and high viscosity are undesirable, such as in fortified beverages, drinkable yogurts, or protein supplements. The extract may also have relevance as a weight-loss supplement. Therefore, we expect that incorporating ñuña protein in processed foods would be a straightforward process.