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Background Breast cancer (BC) is the most commonly diagnosed cancer and the second leading cause of cancer-related deaths among women in Africa after cervical cancer. Even if the epidemiological data are now aligned with those relating to industrialized countries, the knowledge concerning breast cancer in Africa, particularly in Western Africa, still lack clinical data, medical treatments, and the evaluation of genetic and non-genetic factors implicated in the etiology of the disease. The early onset and the aggressiveness of diagnosed breast cancers in patients of African ancestry strongly suggest that the genetic risk factor may be a key component, but so far, very few studies on the impact of germ line mutations in breast cancer in Africa have been conducted, with negative consequences on prevention, awareness and patient management. Through Next Generation sequencing (NGS), we analyzed all of the coding regions and the exon–intron junctions of BRCA1 and BRCA2 genes—the two most important genes in hereditary breast cancer—in fifty-one women from Burkina Faso with early onset of breast cancer with or without a family history. Results We identified six different pathogenic mutations (three in BRCA1, three in BRCA2), two of which were recurrent in eight unrelated women. Furthermore, we identified, in four other patients, two variants of uncertain clinical significance (VUS) and two variants never previously described in literature, although one of them is present in the dbSNP database. Conclusions This is the first study in which the entire coding sequence of BRCA genes has been analyzed through Next Generation Sequencing in Burkinabe young women with breast cancer. Our data support the importance of genetic risk factors in the etiology of breast cancer in this population and suggest the necessity to improve the genetic cancer risk assessment. Furthermore, the identification of the most frequent mutations of BRCA1 and BRCA2 in the population of Burkina Faso will allow the development of an inexpensive genetic test for the identification of subjects at high genetic cancer risk, which could be used to design personalized therapeutic protocols.

Coronary artery disease (CAD) and its major complication, acute myocardial infarction (AMI), are the leading causes of disability and death worldwide. An individual's risk of developing CAD and MI is modulated by an interplay between genetic and lifestyle factors. It is now clear that epigenetics may play a central role in the development of CAD because epigenetic patterns are affected by the environment and can modulate gene expression. Here, the authors discuss the major epigenetic changes that contribute to CAD and the latest discoveries on the influence of the environment on epigenetic profiles in the development of CAD.

Background: Breast cancer (BC) is the most commonly diagnosed cancer and the second leading cause of cancer-related deaths, after cervical cancer, among women in Africa. Even if the epidemiological data are now aligned with those relating to industrialized countries, the knowledge concerning breast cancer in Africa, in particularly in Western Africa still lack clinical data, medical treatments, and the evaluation of genetic and non-genetic factors implicated in the etiology of the disease.The early onset and the aggressiveness of diagnosed breast cancers in patients of African ancestry strongly suggest that the genetic risk factor may play an important role but up to date very few studies have been done concerning the impact of germ line mutations in breast cancer in Africa, with a negative impact on prevention, awareness and patient management.We have performed by Next Generation sequencing (NGS) the analysis of all coding regions and the exon-intron junctions of BRCA1 and BRCA2 genes, the two most important genes in hereditary breast cancer, in fifty-one women from Burkina Faso with early onset of breast cancer and or without a family history.Results: We identified six different pathogenic mutations (3 in BRCA1, 3 in BRCA2), two of which have been found to be recurrent , in 8 unrelated women.In addition, we identified, in 4 other patients, two variants of uncertain clinical significance (VUS) and two variants never previously described in literature, although one of which is present in the dbSNP database.Conclusions: The present study is the first in which the entire coding sequence of BRCA genes have been analyzed by Next Generation Sequencing in Burkinabe young women with breast cancer. Our data support the importance of genetic risk factors in the etiology of breast cancer in this population and suggests the necessity to improve the genetic cancer risk assessment. Furthermore, the identification of the most frequent mutations of BRCA1 and BRCA2 in the population of Burkina Faso will allow the development of an inexpensive genetic test for the identification of subjects at high genetic cancer risk, which could be used to design personalized therapeutic protocols.

SARS-CoV-2 is responsible for the ongoing world-wide pandemic which has already taken more than two million lives. Effective treatments are urgently needed. The enzymatic activity of the HECT-E3 ligase family members has been implicated in the cell egression phase of deadly RNA viruses such as Ebola through direct interaction of its VP40 Protein. Here we report that HECT-E3 ligase family members such as NEDD4 and WWP1 interact with and ubiquitylate the SARS-CoV-2 Spike protein. Furthermore, we find that HECT family members are overexpressed in primary samples derived from COVID-19 infected patients and COVID-19 mouse models. Importantly, rare germline activating variants in the NEDD4 and WWP1 genes are associated with severe COVID-19 cases. Critically, I3C, a natural NEDD4 and WWP1 inhibitor from Brassicaceae, displays potent antiviral effects and inhibits viral egression. In conclusion, we identify the HECT family members of E3 ligases as likely novel biomarkers for COVID-19, as well as new potential targets of therapeutic strategy easily testable in clinical trials in view of the established well-tolerated nature of the Brassicaceae natural compounds.

Coronary artery disease (CAD) and its major complication, acute myocardial infarction (AMI), are the leading causes of disability and death worldwide. An individual's risk of developing CAD and MI is modulated by an interplay between genetic and lifestyle factors. It is now clear that epigenetics may play a central role in the development of CAD because epigenetic patterns are affected by the environment and can modulate gene expression. Here, the authors discuss the major epigenetic changes that contribute to CAD and the latest discoveries on the influence of the environment on epigenetic profiles in the development of CAD.

For the evaluation of the expression level of each miRNA was used the Ct (threshold cycle) method quantification. The threshold cycle (Ct) is defined as the PCR cycle at which the fluorescent signal of the reporter dye crosses an arbitrarily placed threshold. This method allows to quantify the absolute expression of each miRNAs in each sample analyzed and then to calculate the different expression of each miRNA in sample versus the controls.

A total of 99 patients has been enrolled to study circulating microRNAs, as diagnostic biomarkers, in patients with chronic stable coronary artery disease (CAD) and with acute myocardial infarction (AMI). For each patient, we have collected 10 mL of whole blood. All the samples have been processed maintaining the same conditions and timing. The samples with hemolysis and clots have been excluded from the study.

The qRT-PCR expression analyses were performed on all the recruited patients (61 CAD, 38 AMI_T0 and 11 AMI_T1 patients respectively). Since the absence of a universally recognized miRNA with housekeeping properties, we have analyzed the amplification curve of 84 circulating microRNAs using the Human Serum & Plasma miScript miRNA PCR Array (MIHS-106ZA, QIAGEN).

Coronary artery disease (CAD) and acute myocardial infarction (AMI) are the leading causes of death worldwide. Since only a subset of CAD patients develops myocardial infarction, it is likely that unique factors predispose to AMI. Circulating microRNAs represent diagnostic powerful biomarkers for detection of heart injuries and patients' risk stratification. Using an array-based approach, the expression of 84 circulating miRNAs was analyzed in plasma of pooled stable CAD patients (CAD; n = 5) and unstable CAD patients (AMI_T0; n = 5) enrolled within 24 hours from an AMI event. The array experiments showed 27 miRNAs differentially expressed with a two-fold up- or down-regulation (10 up- and 17 down-regulated miRNAs). Among them, miR-423-5p dis-regulation was confirmed in a larger case study (n = 99). Circulating miR-423-5p resulted to be significantly down-regulated within 24 hours from the AMI event (FC = -2, p≤0.05). Interestingly, miR-423-5p expression resulted to be increased (FC = +2; p≤0.005) in a subgroup of the same AMI patients (AMI_T1; n = 11) analyzed after 6 months from the acute event. We extended miR-423-5p expression study on PBMCs (peripheral blood mononuclear cells), confirming also in this tissue its up-regulation at 6 months post-AMI. Receiver operating characteristic analyses (ROC) were performed to detect the power of miR-423-5p to discriminate stable and unstable CAD. In plasma, miR-423-5p expression accurately distinguishes stable and unstable CAD patients (AUC = 0.7143, p≤0.005). Interestingly, the highest discriminatory value (AUC = 0.8529 p≤0.0005) was identified in blood cells, where miR-423-5p expression is able to differentiate unstable CAD patients during an acute event (AMI_T0) from those at six months post-AMI (AMI_T1). Furthermore, cellular miR-423-5p may discriminate also stable CAD patients from unstable CAD patients after six months post-AMI (AUC = 0.7355 p≤0.05). The results of this pilot-study suggest that miR-423-5p expression level both in plasma and blood cells, could represent a new promising biomarker for risk stratification of CAD patients.

Long non-coding RNAs (lncRNAs) are a class of regulatory RNAs capable of binding DNA, RNA, and/or protein to regulate transcriptional and epigenetic networks. Although thousands of lncRNAs have been identified, relatively few have been functionally characterized. Here we identify a primate-specific lncRNA, CHROME , encoded in a locus associated with cardiovascular disease. We found that CHROME expression is increased in the plasma of patients with inflammatory conditions, including coronary artery disease and lupus, compared to control subjects. Using FANTOM, a database of transcriptome analyses, we found the CHROME locus is transcriptionally activated in human monocytes and macrophages stimulated with microbial ligands and inflammatory cytokines. To investigate CHROME’s molecular mechanisms, we used RNA immunoprecipitation (RIP) and chromatin isolation by RNA purification (ChIRP) to map CHROME lncRNA -protein and -DNA interactions, respectively. We found that CHROME has a strong histone binding affinity and its DNA binding pattern was consistent with interaction of CHROME with numerous inflammatory transcription factor motifs, including sites for CEBPβ, SPI1, NFKB, and RELA. To investigate the impact of CHROME’s interaction with DNA in macrophages, we used gain and loss of function studies combined with RNA-sequencing. Ingenuity Pathway Analysis of genes most significantly altered with both CHROME knockdown and overexpression identified the inflammatory response as the pathway most significantly altered by CHROME . In particular, repression of CHROME led to a decrease in the expression of interferon stimulated genes and receptors involved in macrophage motility. Together, these data suggest that CHROME contributes to the transcriptional regulation of inflammatory gene expression and its dysregulation in the setting of atherosclerotic cardiovascular disease may contribute to the maintenance of chronic inflammation.

Alternative splicing (AS) is a process in which precursor messenger RNA (pre-mRNA) splicing sites are differentially selected to diversify the protein isoform population. Changes in AS patterns have an essential role in normal development, differentiation and response to physiological stimuli. It is documented that AS can generate both “risk” and “protective” splice variants that can contribute to the pathogenesis of several diseases including atherosclerosis. The main endothelial receptor for oxidized low-density lipoprotein (ox-LDLs) is LOX-1 receptor protein encoded by the OLR1 gene. When OLR1 undergoes AS events, it generates three variants: OLR1, OLR1D4 and LOXIN. The latter lacks exon 5 and two-thirds of the functional domain. Literature data demonstrate a protective role of LOXIN in pathologies correlated with LOX-1 overexpression such as atherosclerosis and tumors. In this review, we summarize recent developments in understanding of OLR1 AS while also highlighting data warranting further investigation of this process as a novel therapeutic target.

The up‐regulation of lectin‐like oxidized low‐density lipoprotein receptor‐1 (LOX‐1), encoded by the OLR1 gene, plays a fundamental role in the pathogenesis of atherosclerosis. Moreover, OLR1 polymorphisms were associated with increased susceptibility to acute myocardial infarction (AMI) and coronary artery diseases (CAD). In these pathologies, the identification of therapeutic approaches that can inhibit or reduce LOX‐1 overexpression is crucial. Predictive analysis showed a putative hsa‐miR‐24 binding site in the 3′UTR of OLR1, ‘naturally’ mutated by the presence of the rs1050286 single nucleotide polymorphism (SNP). Luciferase assays revealed that miR‐24 targets OLR1 3′UTR‐G, but not 3′UTR‐A (P < 0.0005). The functional relevance of miR‐24 in regulating the expression of OLR1 was established by overexpressing miR‐24 in human cell lines heterozygous (A/G, HeLa) and homozygous (A/A, HepG2) for rs1050286 SNP. Accordingly, HeLa (A/G), but not HepG2 (A/A), showed a significant down‐regulation of OLR1 both at RNA and protein level. Our results indicate that rs1050286 SNP significantly affects miR‐24 binding affinity to the 3′UTR of OLR1, causing a more efficient post‐transcriptional gene repression in the presence of the G allele. On this basis, we considered that OLR1 rs1050286 SNP may contribute to modify OLR1 susceptibility to AMI and CAD, so ORL1 SNPs screening could help to stratify patients risk.