Living with the enemy: from protein-misfolding pathologies we know, to those we want to know

Conformational diseases are caused by the aggregation of misfolded proteins. The risk for such pathologies develops years before clinical symptoms appear, and is higher in people with alpha-1 antitrypsin (AAT) polymorphisms. Thousands of people with alpha-1 antitrypsin deficiency (AATD) are underdiagnosed. Enemyaggregating proteins may reside in these underdiagnosed AATD patients for many years before a pathology for AATD fully develops. In this perspective review, we hypothesize that the AAT protein could exert a new and previously unconsidered biological effect as an endogenous metal ion chelator that plays a significant role in essential metal ion homeostasis. In this respect, AAT polymorphism may cause an imbalance of metal ions, which could be correlated with the aggregation of amylin, tau, amyloid beta, and alpha synuclein proteins in type 2 diabetes mellitus (T2DM), Alzheimer’s and Parkinson’s diseases, respectively

NuMA Overexpression in Epithelial Ovarian Cancer

Highly aneuploid tumours are common in epithelial ovarian cancers (EOC). We investigated whether NuMA expression was associated with this phenomenon

Expression analysis of the MCPH1/BRIT1 and BRCA1 tumor suppressor genes and telomerase splice variants in epithelial ovarian cancer.

Aims The aim of this study was to explore the correlation of hTERT splice variant expression with MCPH1/BRIT1 and BRCA1 expression in epithelial ovarian cancer (EOC) samples. Background Telomerase activation can contribute to the progression of tumors and the development of cancer. However, the regulation of telomerase activity remains unclear. MCPH1 (also known as BRIT1, BRCT-repeat inhibitor of hTERT expression) and BRCA1 are tumor suppressor genes that have been linked to telomerase expression. Methods qPCR was used to investigate telomerase splice variants, MCPH1/BRIT1 and BRCA1 expression in EOC tissue and primary cultures. Results The wild type α+/β+ hTERT variant was the most common splice variant in the EOC samples, followed by α+/β− hTERT, a dominant negative regulator of telomerase activity. EOC samples expressing high total hTERT demonstrated significantly lower MCPH1/BRIT1 expression in both tissue (p = 0.05) and primary cultures (p = 0.03). We identified a negative correlation between MCPH1/BRIT1 and α+/β+ hTERT (p = 0.04), and a strong positive association between MCPH1/BRIT1 and both α−/β+ hTERT and α−/β− hTERT (both p = 0.02). A positive association was observed between BRCA1 and α−/β+ hTERT and α−/β− hTERT expression (p = 0.003 and p = 0.04, respectively). Conclusions These findings support a regulatory effect of MCPH1/BRIT1 and BRCA1 on telomerase activity, particularly the negative association between MCPH1/BRIT1 and the functional form of hTERT (α+/β+)

Protective potential of mesenchymal stem cells against COVID-19 during pregnancy

SARS-CoV-2 causes COVID-19. COVID-19 has led to severe clinical illnesses and an unprecedented death toll. The virus induces immune inflammatory responses specifically cytokine storm in lungs. Several published reports indicated that pregnant females are less likely to develop severe symptoms compared with non-pregnant. Putative protective role of maternal blood circulating fetal mesenchymal stem cells (MSCs) has emerged and have been put forward as an explanation to alleviated symptoms. MSCs with immune-modulatory, anti-inflammatory and anti-viral roles, hold great potential for the treatment of COVID-19. MSCs could be an alternative to treat infections resulting from the SARS-CoV-2 and potential future outbreaks. This review focuses on the MSCs putative protective roles against COVID-19 in pregnant females

Immunohistochemical analysis of Microcephalin and ASPM expression in malignant samples.

<p>Serous adenocarcinoma TMA cores showing nuclear and cytoplasmic Microcephalin (A and B) and ASPM expression (C and D) respectively. White arrow shows nuclear staining and black arrow shows cytoplasmic staining. A and B are 20x, C and D are 40x magnification.</p

Microcephalin nuclear intensity in the training set.

<p>Microcephalin nuclear intensity in the training set.</p

Correlation of cytoplasmic ASPM expression with clinicopathological data in the EOC validation set.

<p>P≤0.05 is significant and are shown in bold.</p

Microcephalin nuclear intensity in the training set.

<p>Microcephalin nuclear intensity in the training set.</p

Cytoplasmic ASPM levels correlate with various clinic-pathological parameters in EOC.

<p>A. Cytoplasmic ASPM levels decrease with grade in serous EOC (continuous data, p<0.0001). B. Cytoplasmic ASPM levels decrease with tumour grade in the serous subtype (discontinuous data, p = 0.0239). C. Cytoplasmic ASPM levels increase with disease stage in endometrioid EOC (discontinuous data, p = 0.0229). D. Cytoplasmic ASPM levels decrease with disease stage in the serous subtype (discontinuous data, p = 0.0017). E. Cytoplasmic ASPM levels decrease with tumour invasion (discontinuous data, p = 0.02). F. High cytoplasmic ASPM levels correlate with no lymph node involvement (p = 0.04). All data analysed using an ANOVA test.</p

Microcephalin expression in EOC validation set samples inversely correlates with tumour stage.

<p>Ai. Normal ovarian epithelial tissue demonstrating high Microcephalin expression levels. Aii-4iv Adenocarcinoma TMA cores showing strong Microcephalin (Aii), moderate Microcephalin (Aiii) and low levels of nuclear Microcephalin expression (Aiv) in stage 1, 2 and 3 tumours respectively. All images are 40x magnification. B. Weak Microcephalin levels in the nucleus are associated with advanced tumour stage (<i>p</i> = 0.0438 using an ANOVA test).</p