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International Journal of Molecular... May 2022Coronavirus disease 2019 (COVID-19) caused by the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become the most severe health crisis,... (Review)
Review
Coronavirus disease 2019 (COVID-19) caused by the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become the most severe health crisis, causing extraordinary economic disruption worldwide. SARS-CoV-2 is a single-stranded RNA-enveloped virus. The process of viral replication and particle packaging is finished in host cells. Viral proteins, including both structural and nonstructural proteins, play important roles in the viral life cycle, which also provides the targets of treatment. Therefore, a better understanding of the structural function of virus proteins is crucial to speed up the development of vaccines and therapeutic strategies. Currently, the structure and function of proteins encoded by the SARS-CoV-2 genome are reviewed by several studies. However, most of them are based on the analysis of SARS-CoV-1 particles, lacking a systematic review update for SARS-CoV-2. Here, we specifically focus on the structure and function of proteins encoded by SARS-CoV-2. Viral proteins that contribute to COVID-19 infection and disease pathogenesis are reviewed according to the most recent research findings. The structure-function correlation of viral proteins provides a fundamental rationale for vaccine development and targeted therapy. Then, current antiviral vaccines are updated, such as inactive viral vaccines and protein-based vaccines and DNA, mRNA, and circular RNA vaccines. A summary of other therapeutic options is also reviewed, including monoclonal antibodies such as a cross-neutralizer antibody, a constructed cobinding antibody, a dual functional monoclonal antibody, an antibody cocktail, and an engineered bispecific antibody, as well as peptide-based inhibitors, chemical compounds, and clustered regularly interspaced short palindromic repeats (CRISPR) exploration. Overall, viral proteins and their functions provide the basis for targeted therapy and vaccine development.
Topics: Antibodies, Viral; Antiviral Agents; COVID-19; Humans; SARS-CoV-2; Viral Proteins; Viral Vaccines
PubMed: 35682761
DOI: 10.3390/ijms23116083 -
BMC Genomics Mar 2022Environmental exposures in utero which modify DNA methylation may have a long-lasting impact on health and disease in offspring. We aimed to identify and replicate...
BACKGROUND
Environmental exposures in utero which modify DNA methylation may have a long-lasting impact on health and disease in offspring. We aimed to identify and replicate previously published genomic loci where DNA methylation changes are attributable to in utero exposures in the NutriGen birth cohort studies Alliance.
METHODS
We reviewed the literature to identify differentially methylated sites of newborn DNA which are associated with the following five traits of interest maternal diabetes, pre-pregnancy body mass index (BMI), diet during pregnancy, smoking, and gestational age. We then attempted to replicate these published associations in the Canadian Healthy Infant Longitudinal Development (CHILD) and the South Asian birth cohort (START) cord blood epigenome-wide data.
RESULTS
We screened 68 full-text articles and identified a total of 17 cord blood epigenome-wide association studies (EWAS) of the traits of interest. Out of the 290 CpG sites reported, 19 were identified in more than one study; all of them associated with maternal smoking. In CHILD and START EWAS, thousands of sites associated with gestational age were identified and maintained significance after correction for multiple testing. In CHILD, there was differential methylation observed for 8 of the published maternal smoking sites. No other traits tested (i.e., folate levels, gestational diabetes, birthweight) replicated in the CHILD or START cohorts.
CONCLUSIONS
Maternal smoking during pregnancy and gestational age are strongly associated with differential methylation in offspring cord blood, as assessed in the EWAS literature and our birth cohorts. There are a limited number of reported methylation sites associated in more than two independent studies related to pregnancy. Additional large studies of diverse populations with fine phenotyping are needed to produce robust epigenome-wide data in order to further elucidate the effect of intrauterine exposures on the infants' methylome.
Topics: Canada; DNA Methylation; Epigenome; Female; Fetal Blood; Genome-Wide Association Study; Humans; Infant, Newborn; Pregnancy
PubMed: 35305575
DOI: 10.1186/s12864-022-08451-6 -
Molecular Ecology Dec 2022Human-driven environmental changes are affecting wildlife across the globe. These challenges do not influence species or populations to the same extent and therefore a... (Meta-Analysis)
Meta-Analysis Review
Human-driven environmental changes are affecting wildlife across the globe. These challenges do not influence species or populations to the same extent and therefore a comprehensive evaluation of organismal health is needed to determine their ultimate impact. Evidence suggests that telomeres (the terminal chromosomal regions) are sensitive to environmental conditions and have been posited as a surrogate for animal health and fitness. Evaluation of their use in an applied ecological context is still scarce. Here, using information from molecular and occupational biomedical studies, we aim to provide ecologists and evolutionary biologists with an accessible synthesis of the links between human disturbances and telomere length. In addition, we perform a systematic review and meta-analysis on studies measuring telomere length in wild/wild-derived animals facing anthropogenic disturbances. Despite the relatively small number of studies to date, our meta-analysis revealed a significant small negative association between disturbances and telomere length (-0.092 [-0.153, -0.031]; n = 28; k = 159). Yet, our systematic review suggests that the use of telomeres as a biomarker to understand the anthropogenic impact on wildlife is limited. We propose some research avenues that will help to broadly evaluate their suitability: (i) further causal studies on the link between human disturbances and telomeres; (ii) investigating the organismal implications, in terms of fitness and performance, of a given telomere length in anthropogenically disturbed scenarios; and (iii) better understanding of the underlying mechanisms of telomere dynamics. Future studies in these facets will help to ultimately determine their role as markers of health and fitness in wildlife facing anthropogenic disturbances.
Topics: Animals; Humans; Animals, Wild; Telomere Shortening; Anthropogenic Effects; Telomere; Biological Evolution
PubMed: 35080073
DOI: 10.1111/mec.16370 -
Neuropsychopharmacology : Official... Mar 2022We searched PubMed for primary research quantifying drug modification of light-induced circadian phase-shifting in rodents. This search, conducted for work published...
We searched PubMed for primary research quantifying drug modification of light-induced circadian phase-shifting in rodents. This search, conducted for work published between 1960 and 2018, yielded a total of 146 papers reporting results from 901 studies. Relevant articles were those with any extractable data on phase resetting in wildtype (non-trait selected) rodents administered a drug, alongside a vehicle/control group, near or at the time of exposure. Most circadian pharmacology experiments were done using drugs thought to act directly on either the brain's central pacemaker, the suprachiasmatic nucleus (SCN), the SCN's primary relay, the retinohypothalamic tract, secondary pathways originating from the medial/dorsal raphe nuclei and intergeniculate leaflet, or the brain's sleep-arousal centers. While the neurotransmitter systems underlying these circuits were of particular interest, including those involving glutamate, gamma-aminobutyric acid, serotonin, and acetylcholine, other signaling modalities have also been assessed, including agonists and antagonists of receptors linked to dopamine, histamine, endocannabinoids, adenosine, opioids, and second-messenger pathways downstream of glutamate receptor activation. In an effort to identify drugs that unduly influence circadian responses to light, we quantified the net effects of each drug class by ratioing the size of the phase-shift observed after administration to that observed with vehicle in a given experiment. This allowed us to organize data across the literature, compare the relative efficacy of one mechanism versus another, and clarify which drugs might best suppress or potentiate phase resetting. Aggregation of the available data in this manner suggested that several candidates might be clinically relevant as auxiliary treatments to suppress ectopic light responses during shiftwork or amplify the circadian effects of timed bright light therapy. Future empirical research will be necessary to validate these possibilities.
Topics: Circadian Rhythm; Pharmaceutical Preparations; S Phase; Serotonin; Suprachiasmatic Nucleus
PubMed: 34961774
DOI: 10.1038/s41386-021-01251-8 -
Medicine Dec 2021DNA damage is a fundamental process that plays a considerable role in generating protein diversity. FANCI, loaded on the altered chromatin, plays a vital role in DNA... (Meta-Analysis)
Meta-Analysis
BACKGROUND
DNA damage is a fundamental process that plays a considerable role in generating protein diversity. FANCI, loaded on the altered chromatin, plays a vital role in DNA damage. Abnormal FANCI expression is potentially associated with carcinogenesis.However, the biological role of FANCI in cervical cancer is yet to be determined.
METHODS
We analyzed FANCI expression via multiple gene expression databases. Genes co-expressed with FANCI and its regulators were identified using LinkedOmics. The correlations between FANCI and cancer immune infiltrates were investigated via Tumor Immune Estimation Resource (TIMER).
RESULTS
FANCI was found upregulated with amplification in tumor tissues of multiple cervical cancer cohorts. High FANCI expression was associated with poorer overall survival (OS). Functional network analysis suggested that FANCI regulates spliceosome, DNA replication, and cell cycle signaling via pathways involving several cancer-related kinases and the E2F family. In additional, FANCI expression was positively correlated with infiltrating levels of CD4+ T and CD8+ T cells, and neutrophils. FANCI expression also showed strong correlations with diverse immune marker sets in cervical cancer.
CONCLUSION
These findings suggested that FANCI is correlated with prognosis of and immune infiltration in cervical cancer, laying a foundation for further study of the immune regulatory role of FANCI in cervical cancer.
Topics: Biomarkers, Tumor; CD8-Positive T-Lymphocytes; Fanconi Anemia Complementation Group Proteins; Female; Gene Expression Regulation; Humans; Lymphocytes, Tumor-Infiltrating; Prognosis; Uterine Cervical Neoplasms
PubMed: 34941027
DOI: 10.1097/MD.0000000000027690 -
Molecules (Basel, Switzerland) Nov 2021Peptides are characterized by their wide range of biological activity: they regulate functions of the endocrine, nervous, and immune systems. The mechanism of such...
Peptides are characterized by their wide range of biological activity: they regulate functions of the endocrine, nervous, and immune systems. The mechanism of such action of peptides involves their ability to regulate gene expression and protein synthesis in plants, microorganisms, insects, birds, rodents, primates, and humans. Short peptides, consisting of 2-7 amino acid residues, can penetrate into the nuclei and nucleoli of cells and interact with the nucleosome, the histone proteins, and both single- and double-stranded DNA. DNA-peptide interactions, including sequence recognition in gene promoters, are important for template-directed synthetic reactions, replication, transcription, and reparation. Peptides can regulate the status of DNA methylation, which is an epigenetic mechanism for the activation or repression of genes in both the normal condition, as well as in cases of pathology and senescence. In this context, one can assume that short peptides were evolutionarily among the first signaling molecules that regulated the reactions of template-directed syntheses. This situation enhances the prospects of developing effective and safe immunoregulatory, neuroprotective, antimicrobial, antiviral, and other drugs based on short peptides.
Topics: Animals; DNA Methylation; Epigenesis, Genetic; Histones; Humans; Peptides; Signal Transduction
PubMed: 34834147
DOI: 10.3390/molecules26227053 -
Frontiers in Physiology 2021Exposure to radiofrequency electromagnetic radiation (RF-EMR) from various wireless devices has increased dramatically with the advancement of technology. One of the...
Exposure to radiofrequency electromagnetic radiation (RF-EMR) from various wireless devices has increased dramatically with the advancement of technology. One of the most vulnerable organs to the RF-EMR is the testes. This is due to the fact that testicular tissues are more susceptible to oxidative stress due to a high rate of cell division and mitochondrial oxygen consumption. As a result of extensive cell proliferation, replication errors occur, resulting in DNA fragmentation in the sperm. While high oxygen consumption increases the level of oxidative phosphorylation by-products (free radicals) in the mitochondria. Furthermore, due to its inability to effectively dissipate excess heat, testes are also susceptible to thermal effects from RF-EMR exposure. As a result, people are concerned about its impact on male reproductive function. The aim of this article was to conduct a review of literature on the effects of RF-EMR emitted by wireless devices on male reproductive hormones in experimental animals and humans. According to the findings of the studies, RF-EMR emitted by mobile phones and Wi-Fi devices can cause testosterone reduction. However, the effect on gonadotrophic hormones (follicle-stimulating hormone and luteinizing hormone) is inconclusive. These findings were influenced by several factors, which can influence energy absorption and the biological effect of RF-EMR. The effect of RF-EMR in the majority of animal and human studies appeared to be related to the duration of mobile phone use. Thus, limiting the use of wireless devices is recommended.
PubMed: 34630149
DOI: 10.3389/fphys.2021.732420 -
PloS One 2021The neuroendocrine stress response allows vertebrates to cope with stressors via the activation of the Hypothalamic-Pituitary-Adrenal (HPA) axis, which ultimately... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The neuroendocrine stress response allows vertebrates to cope with stressors via the activation of the Hypothalamic-Pituitary-Adrenal (HPA) axis, which ultimately results in the secretion of glucocorticoids (GCs). Glucocorticoids have pleiotropic effects on behavior and physiology, and might influence telomere length dynamics. During a stress event, GCs mobilize energy towards survival mechanisms rather than to telomere maintenance. Additionally, reactive oxygen species produced in response to increased GC levels can damage telomeres, also leading to telomere shortening. In our systematic review and meta-analysis, we tested whether GC levels impact telomere length and if this relationship differs among time frame, life history stage, or stressor type. We hypothesized that elevated GC levels are linked to a decrease in telomere length.
METHODS
We conducted a literature search for studies investigating the relationship between telomere length and GCs in non-human vertebrates using four search engines: Web of Science, Google Scholar, Pubmed and Scopus, last searched on September 27th, 2020. This review identified 31 studies examining the relationship between GCs and telomere length. We pooled the data using Fisher's Z for 15 of these studies. All quantitative studies underwent a risk of bias assessment. This systematic review study was registered in the Open Science Framework Registry (https://osf.io/rqve6).
RESULTS
The pooled effect size from fifteen studies and 1066 study organisms shows no relationship between GCs and telomere length (Fisher's Z = 0.1042, 95% CI = 0.0235; 0.1836). Our meta-analysis synthesizes results from 15 different taxa from the mammalian, avian, amphibian groups. While these results support some previous findings, other studies have found a direct relationship between GCs and telomere dynamics, suggesting underlying mechanisms or concepts that were not taken into account in our analysis. The risk of bias assessment revealed an overall low risk of bias with occasional instances of bias from missing outcome data or bias in the reported result.
CONCLUSION
We highlight the need for more targeted experiments to understand how conditions, such as experimental timeframes, stressor(s), and stressor magnitudes can drive a relationship between the neuroendocrine stress response and telomere length.
Topics: Animals; Glucocorticoids; Hypothalamo-Hypophyseal System; Pituitary-Adrenal System; Telomere Shortening; Vertebrates
PubMed: 34597314
DOI: 10.1371/journal.pone.0257370 -
Frontiers in Genetics 2021The triad of drug efficacy, toxicity and resistance underpins the risk-benefit balance of all therapeutics. The application of pharmacogenomics has the potential to...
The triad of drug efficacy, toxicity and resistance underpins the risk-benefit balance of all therapeutics. The application of pharmacogenomics has the potential to improve the risk-benefit balance of a given therapeutic via the stratification of patient populations based on DNA variants. A growth in the understanding of the particulars of the mitochondrial genome, alongside the availability of techniques for its interrogation has resulted in a growing body of literature examining the impact of mitochondrial DNA (mtDNA) variation upon drug response. To critically evaluate and summarize the available literature, across a defined period, in a systematic fashion in order to map out the current landscape of the subject area and identify how the field may continue to advance. A systematic review of the literature published between January 2009 and December 2020 was conducted using the PubMed database with the following key inclusion criteria: reference to specific mtDNA polymorphisms or haplogroups, a core objective to examine associations between mtDNA variants and drug response, and research performed using human subjects or human models. Review of the literature identified 24 articles reporting an investigation of the association between mtDNA variant(s) and drug efficacy, toxicity or resistance that met the key inclusion criteria. This included 10 articles examining mtDNA variations associated with antiretroviral therapy response, 4 articles examining mtDNA variants associated with anticancer agent response and 4 articles examining mtDNA variants associated with antimicrobial agent response. The remaining articles covered a wide breadth of medications and were therefore grouped together and referred to as "other." Investigation of the impact of mtDNA variation upon drug response has been sporadic to-date. Collective assessment of the associations identified in the articles was inconclusive due to heterogeneous methods and outcomes, limited racial/ethnic groups, lack of replication and inadequate statistical power. There remains a high degree of idiosyncrasy in drug response and this area has the potential to explain variation in drug response in a clinical setting, therefore further research is likely to be of clinical benefit.
PubMed: 34484295
DOI: 10.3389/fgene.2021.698825 -
Cells Jun 2021Telomeres are aging biomarkers, as they shorten while cells undergo mitosis. The aim of this study was to evaluate whether psychiatric disorders marked by psychological...
Telomeres are aging biomarkers, as they shorten while cells undergo mitosis. The aim of this study was to evaluate whether psychiatric disorders marked by psychological distress lead to alterations to telomere length (TL), corroborating the hypothesis that mental disorders might have a deeper impact on our physiology and aging than it was previously thought. A systematic search of the literature using MeSH descriptors of psychological distress ("Traumatic Stress Disorder" or "Anxiety Disorder" or "depression") and telomere length ("cellular senescence", "oxidative stress" and "telomere") was conducted on PubMed, Cochrane Library and ScienceDirect databases. A total of 56 studies (113,699 patients) measured the TL from individuals diagnosed with anxiety, depression and posttraumatic disorders and compared them with those from healthy subjects. Overall, TL negatively associates with distress-related mental disorders. The possible underlying molecular mechanisms that underly psychiatric diseases to telomere shortening include oxidative stress, inflammation and mitochondrial dysfunction linking. It is still unclear whether psychological distress is either a cause or a consequence of telomere shortening.
Topics: Humans; Mental Disorders; Mitochondria; Oxidative Stress; Telomere; Telomere Shortening
PubMed: 34200513
DOI: 10.3390/cells10061423