Climate change, human health, and the exposome: Utilizing OMIC technologies to navigate an era of uncertainty.

Climate change is an anthropogenic phenomenon that is alarming scientists and non-scientists alike. The emission of greenhouse gases is causing the temperature of the earth to rise and this increase is accompanied by a multitude of climate change-induced environmental exposures with potential health impacts. Tracking human exposure has been a major research interest of scientists worldwide. This has led to the development of exposome studies that examine internal and external individual exposures over their lifetime and correlate them to health. The monitoring of health has also benefited from significant technological advances in the field of "omics" technologies that analyze physiological changes on the nucleic acid, protein, and metabolism levels, among others. In this review, we discuss various climate change-induced environmental exposures and their potential health implications. We also highlight the potential integration of the technological advancements in the fields of exposome tracking, climate monitoring, and omics technologies shedding light on important questions that need to be answered.

Prognostic MicroRNA Panel for HCV-Associated HCC: Integrating Computational Biology and Clinical Validation.

Early detection of hepatocellular carcinoma (HCC) will reduce morbidity and mortality rates of this widely spread disease. Dysregulation in microRNA (miRNA) expression is associated with HCC progression. The objective is to identify a panel of differentially expressed miRNAs (DE-miRNAs) to enhance HCC early prediction in hepatitis C virus (HCV) infected patients. Candidate miRNAs were selected using a bioinformatic analysis of microarray and RNA-sequencing datasets, resulting in nine DE-miRNAs (miR-142, miR-150, miR-183, miR-199a, miR-215, miR-217, miR-224, miR-424, and miR-3607). Their expressions were validated in the serum of 44 healthy individuals, 62 non-cirrhotic HCV patients, 67 cirrhotic-HCV, and 72 HCV-associated-HCC patients using real-time PCR (qPCR). There was a significant increase in serum concentrations of the nine-candidate miRNAs in HCC and HCV patients relative to healthy individuals. MiR-424, miR-199a, miR-142, and miR-224 expressions were significantly altered in HCC compared to non-cirrhotic patients. A panel of five miRNAs improved sensitivity and specificity of HCC detection to 100% and 95.12% relative to healthy controls. Distinguishing HCC from HCV-treated patients was achieved by 70.8% sensitivity and 61.9% specificity using the combined panel, compared to alpha-fetoprotein (51.4% sensitivity and 60.67% specificity). These preliminary data show that the novel miRNAs panel (miR-150, miR-199a, miR-224, miR-424, and miR-3607) could serve as a potential non-invasive biomarker for HCC early prediction in chronic HCV patients. Further prospective studies on a larger cohort of patients should be conducted to assess the potential prognostic ability of the miRNAs panel.

RNA Vaccines against Infectious Diseases: Vital Progress with Room for Improvement.

mRNA vaccines have amassed a strong interest from scientists and nonscientists alike for their potential in treating cancer and curbing the spread of infectious diseases. Their success has been bolstered by the COVID-19 pandemic as mRNA vaccines for the SARS-CoV-2 virus showed unrivaled efficiency and success. The strategy relies on the delivery of an RNA transcript that carries the sequence of an antigenic molecule into the body's cells where the antigen is manufactured. The lack of use of infectious pathogens and the fact that they are made of nucleic acids render these vaccines a favorable alternative to other vaccination modalities. However, mRNA vaccination still suffers from a great deal of hurdles starting from their safety, cellular delivery, uptake and response to their manufacturing, logistics and storage. In this review, we examine the premise of RNA vaccination starting from their conceptualization to their clinical applications. We also thoroughly discuss the advances in the field of RNA vaccination for infectious diseases. Finally, we discuss the challenges impeding their progress and shed light on potential areas of research in the field.

Bioinformatics Analysis of Allele Frequencies and Expression Patterns of ACE2, TMPRSS2 and FURIN in Different Populations and Susceptibility to SARS-CoV-2.

The virus responsible for the COVID-19 global health crisis, SARS-CoV-2, has been shown to utilize the ACE2 protein as an entry point to its target cells. The virus has been shown to rely on the actions of TMPRSS2 (a serine protease), as well as FURIN (a peptidase), for the critical priming of its spike protein. It has been postulated that variations in the sequence and expression of SARS-CoV-2's receptor (ACE2) and the two priming proteases (TMPRSS2 and FURIN) may be critical in contributing to SARS-CoV-2 infectivity. This study aims to examine the different expression levels of FURIN in various tissues and age ranges in light of ACE2 and TMPRSS2 expression levels using the LungMAP database. Furthermore, we retrieved expression quantitative trait loci (eQTLs) of the three genes and their annotation. We analyzed the frequency of the retrieved variants in data from various populations and compared it to the Egyptian population. We highlight FURIN's potential interplay with the immune response to SARS-CoV-2 and showcase a myriad of variants of the three genes that are differentially expressed across populations. Our findings provide insights into potential genetic factors that impact SARS-CoV-2 infectivity in different populations and shed light on the varying expression patterns of FURIN.

COVID-19 Genetic and Environmental Risk Factors: A Look at the Evidence.

The Covid-19 pandemic is with no doubt the biggest health crisis of the 21st century. The disease is caused by a virus of the Coronaviridae family and is closely related to the virus responsible for the severe acute respiratory Syndrome (SARS). Since December 2019, the virus has continued to spread way beyond the location of the first recorded cases (Wuhan, China). As of now, over 5 million cases have been diagnosed with the disease worldwide and over 300 thousand have died. COVID-19 patients suffer from respiratory symptoms that can rapidly turn into potentially fatal acute respiratory distress syndrome (ARDS) in a portion of patients. Although many drugs and vaccines are currently under clinical trials, there is no currently approved treatment or vaccine. It is therefore critical to correctly identify risk factors that lead to the exacerbation of symptoms in highly susceptible groups. Groups that are at high risk include those aged 55 or older especially those with underlying conditions such as cardiovascular diseases. Certain ethnicities such as African-Americans have been found to be at a higher risk and males seem to be higher both in numbers as well as severity of cases. It is hypothesized that these groups are at risk as their molecular landscape is more permissive of viral infection and growth. Different occupations, especially those related to health-care as well as populations that do not cultivate a mask-wearing culture are at higher risk due to environmental exposure. In this article, we examine the evidence regarding different groups that are more sensitive to the disease and review hypotheses pertaining to COVID-19 infection and prognosis. Risk factors that can be related to the molecular landscape of COVID-19 infection as well as those related to environmental and occupational conditions are discussed.

Emerging role of nutrition and the non-coding landscape in type 2 diabetes mellitus: A review of literature.

With the advent of recent advances in molecular techniques and whole genome sequencing, we have come to know that the non-coding landscape (including non-coding RNAs, tRNAs and even telomeres) plays a major role in the regulation of cellular processes. Furthermore, the deregulation of this landscape has been found to contribute to and even bring about the pathogenesis of a large number of diseases. One of such diseases is diabetes mellitus (type 2 specifically) whose incidence rate and global burden is constantly increasing. Nutrition has been proven to be a key player in the development, onset and control of type 2 diabetes mellitus. Additionally, non-coding DNA based molecular markers are emerging as biomarkers of T2D, susceptibility, and perhaps dietary supplements can modulate non-coding DNA based markers expression and function in T2D management. In this review, we provide a brief overview of the developmental origins and genetics of type 2 diabetes mellitus, how each component of the non-coding landscape contributes to the development and progression of the disease and finally we discuss how dietary interventions modulate the non-coding landscape in T2D.

Dual approach for the colorimetric determination of unamplified microRNAs by using citrate capped gold nanoparticles.

The authors describe a method for the colorimetric determination of unamplified microRNA. It is based on the use of citrate-capped gold nanoparticles (AuNPs) and, alternatively, a microRNA-probe hybrid or a magnetically extracted microRNA that serve as stabilizers against the salt-induced aggregation of AuNPs. The absorbance ratios A525/A625 of the reacted AuNP solutions were used to quantify the amount of microRNA. The assay works in the range of 5-25 pmol microRNA. The lower limit of detection (LOD) is 10 pmol. The performance of the method was tested by detection of microRNA-210-3p in totally extracted urinary microRNA from normal, benign, and bladder cancer subjects. The sensitivity and specificity for qualitative detection of urinary microRNA-210-3p using the assay are 74% and 88% respectively, which is consistent with real time PCR based assays. The assay was applied to the determination of specific microRNA by using its specific oligo targeter or following magnetic isolation of the desired microRNA. The method is simple, cost-efficient, has a short turn-around time and requires minimal equipment and personnel. Graphical abstract Schematic of the two detection schemes: In the first approach, matched microRNA hybridizes with its specific probe to stabilize gold nanoparticles (AuNPs) against salt induced aggregation and to leave the red color of the AuNPs unchanged. In the second one, microRNA extracted via magnetic nanoparticles (MNP) stabilizes AuNPs against aggregation.

Investigating miRNA-661 and ATG4-B mRNA expression as potential biomarkers for hepatocellular carcinoma.

AIM: We aimed to examine the statistical association between serum expression of miRNA 661 (miR-661) and ATG-4B mRNA and hepatocellular carcinoma (HCC) based on in silico data analysis followed by clinical validation. PATIENTS & METHODS: Quantitative reverse-transcriptase real-time PCR was used to examine the expression of miR-661 and ATG-4B mRNA in the sera of HCC patients versus control. RESULTS: The expression of miR-661 and ATG-4B mRNA was positive in 97.14 and 77.14%, respectively, in HCC patients. The survival analysis showed that ATG-4B mRNA was an independent prognostic factor. CONCLUSION: Our data are the first report of its kind regarding the considerable clinical significance of miR-661 and ATG-4B mRNA in HCC patients.