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International Journal of Molecular... Aug 2023PARPi, in combination with ionizing radiation, has demonstrated the ability to enhance cellular radiosensitivity in different tumors. The rationale is that the exposure...
PARPi, in combination with ionizing radiation, has demonstrated the ability to enhance cellular radiosensitivity in different tumors. The rationale is that the exposure to radiation leads to both physical and biochemical damage to DNA, prompting cells to initiate three primary mechanisms for DNA repair. Two double-stranded DNA breaks (DSB) repair pathways: (1) non-homologous end-joining (NHEJ) and (2) homologous recombination (HR); and (3) a single-stranded DNA break (SSB) repair pathway (base excision repair, BER). In this scenario, PARPi can serve as radiosensitizers by leveraging the BER pathway. This mechanism heightens the likelihood of replication forks collapsing, consequently leading to the formation of persistent DSBs. Together, the combination of PARPi and radiotherapy is a potent oncological strategy. This combination has proven its efficacy in different tumors. However, in prostate cancer, there are only preclinical studies to support it and, recently, an ongoing clinical trial. The objective of this paper is to perform a review of the current evidence regarding the use of PARPi and radiotherapy (RT) in PCa and to give future insight on this topic.
Topics: Humans; Male; DNA Repair; Medical Oncology; Poly(ADP-ribose) Polymerase Inhibitors; Prostatic Neoplasms; Radiation Oncology
PubMed: 37629155
DOI: 10.3390/ijms241612978 -
Sports Medicine - Open Sep 2019There is abundant and mounting information related to the molecular and biological structure and function of the Aquaporin-1 (AQP1) gene and the AQP1-Aquaporin channel.... (Review)
Review
BACKGROUND
There is abundant and mounting information related to the molecular and biological structure and function of the Aquaporin-1 (AQP1) gene and the AQP1-Aquaporin channel. Regulation of water flow across cell membranes is essential for supporting inter- and intracellular fluid balance, which is critical for health and exercise performance. The transmembrane water channel AQP1 is important for cardiorespiratory endurance (CE) because it influences fluid transfers in erythrocytes, endothelial, and pulmonary cells and is vital for transport of ammonium, bicarbonate, carbon dioxide, glycerol, nitric oxide, potassium ion, water, and trans-epithelial and renal water. Very recent publications suggest the association between a DNA sequence variant, rs1049305 (C > G), in the 3'-untranslated region of the AQP1 gene and CE performance. Other reports indicate further significant associations between AQP1 channel and CE phenotypes. The purposes of this systematic review were to examine the extent of the associations between the AQP1 rs1049305 genotype and CE exercise performance and body fluid loss in long-distance runners and AQP1 channel associations with other CE phenotypes.
METHODS
Data sources: A comprehensive review was conducted using PubMed, EMBASE, CINAHL, and Cochrane electronic databases. The search ranged from January 1, 1988, to December 31, 2018. Studies reported in English, French, and Spanish were considered. Eligibility criteria: The criteria for inclusion in the review were (a) case-control study; (b) unequivocal definition of cases and controls; (c) CE was defined as performance in endurance events, laboratory tests, and/or maximal oxygen consumption; (d) exclusion criteria of known causes; (e) genotyping performed by PCR or sequencing; (f) genotype frequencies reported; and (g) no deviation of genotype frequencies from Hardy-Weinberg equilibrium in the control group. Study appraisal: The systematic review included studies examining the AQP1 gene and AQP1 channel structure and function, associations between the AQP1 gene sequence variant rs1049305 (C > G) and CE performance, body fluid loss in long-distance runners, and other studies reporting on the AQP1 gene and channel CE phenotype associations. Synthesis methods: For each selected study, the following data were extracted: authors, year of publication, sample size and number of cases and controls, CE definition, exclusion criteria, inclusion criteria for cases and controls, methods used for genotyping, genotype, allele frequencies and HWE for genotype frequencies in cases and control groups, and method of AQP1 gene and AQP1 channel analysis.
RESULTS
The initial databases search found 172 pertinent studies. Of those, 46 studies were utilized in the final synthesis of the systematic review. The most relevant findings were (a) the identification of an independent replication of the association between AQP1 gene sequence variant rs1049305 (C > G) and CE performance; (b) the association of the rs1049305 C-allele with faster CE running performance; (c) in knockout model, using a linear regression analysis of distance run as a function of Aqp1 status (Aqp1-null vs. wild-type mice) and conditions of hypoxia (ambient [O] = 16%), normoxia (21%), and hyperoxia (40%) indicated that the Aqp1 knockout ran less distance than the wild-type mice (p < 0.001); (d) in vitro, a reduced AQP1 expression was associated with the presence of the rs1049305 G-allele; (e) AQP1 null humans led normal lives and were entirely unaware of any physical limitations. However, they could not support fluid homeostasis when exposed to chronic fluid overload. The limited number of studies with "adequate sample sizes" in various racial and ethnic groups precluding to perform proper in-depth statistical analysis.
CONCLUSIONS
The AQP1 gene and AQP1 channel seems to support homeostatic mechanisms, yet to be totally understood, that are auxiliary in achieving an advantage during endurance exercise. AQP1 functions are vital during exercise and have a profound influence on endurance running performance. AQP1s are underappreciated structures that play vital roles in cellular homeostasis at rest and during CE endurance running exercise. The outcome of the present systematic review provide support to the statement of hypotheses and further research endeavors on the likely influence of AQP1 gene and AQP1 channel on CE performance. Registration: The protocol is not registered.
PubMed: 31486928
DOI: 10.1186/s40798-019-0213-0 -
Ecotoxicology and Environmental Safety Apr 2024Although the association between changes in human telomere length (TL) and ambient fine particulate matter (PM) has been documented, there remains disagreement among the... (Meta-Analysis)
Meta-Analysis Review
Although the association between changes in human telomere length (TL) and ambient fine particulate matter (PM) has been documented, there remains disagreement among the related literature. Our study conducted a systematic review and meta-analysis of epidemiological studies to investigate the health effects of outdoor PM exposure on human TL after a thorough database search. To quantify the overall effect estimates of TL changes associated with every 10 μg/m increase in PM exposure, we focused on two main topics, which were outdoor long-term exposure and prenatal exposure of PM. Additionally, we included a summary of short-term PM exposure and its impact on TL due to limited data availability. Our qualitative analysis included 20 studies with 483,600 participants. The meta-analysis showed a statistically significant association between outdoor PM exposure and shorter human TL, with pooled impact estimates (β) of -0.12 (95% CI: -0.20, -0.03, I= 95.4%) for general long-term exposure and -0.07 (95% CI: -0.15, 0.00, I= 74.3%) for prenatal exposure. In conclusion, our findings suggest that outdoor PM exposure may contribute to TL shortening, and noteworthy associations were observed in specific subgroups, suggesting the impact of various research variables. Larger, high-quality studies using standardized methodologies are necessary to strengthen these conclusions further.
Topics: Female; Pregnancy; Humans; Particulate Matter; Air Pollution; Prenatal Exposure Delayed Effects; Telomere Shortening; Telomere; Air Pollutants; Environmental Exposure
PubMed: 38518608
DOI: 10.1016/j.ecoenv.2024.116206 -
The Journal of the Egyptian Public... Jul 2023Occult hepatitis B virus (HBV) infection (OBI) is a major public health problem. The clinical importance of OBI stems from the fact that it can be transmitted to healthy... (Review)
Review
BACKGROUND
Occult hepatitis B virus (HBV) infection (OBI) is a major public health problem. The clinical importance of OBI stems from the fact that it can be transmitted to healthy individuals at extremely low viral load levels. Additionally, immunosuppression has the potential to trigger viral replication, which can result in life-threatening liver decompensation. Despite several studies examining the prevalence of OBI, the pooled prevalence of OBI in Egypt remains unknown, particularly among blood donors and high-risk individuals, to whom intervention should be targeted.
METHODS
A comprehensive literature search of the following databases was conducted from inception to October 2022 using the following keywords: occult hepatitis B virus infection or occult HBV infection or OBI and Egypt in MEDLINE [PubMed], Scopus, Google Scholar, and Web of Science. The review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement. I-squared and Cochran's Q were used to measure the heterogeneity between the studies, and based on the random effects model, results were reported as proportions (%) with a 95% confidence interval (CI). Analyses of subgroup analyses were conducted based on the target population. Sensitivity analyses were conducted using the leave-one-out approach to test the robustness of the results.
RESULTS
A total of 50 studies with 62 estimations of OBI were included, 19 in patients who were HBsAg-negative and anti-HBc-positive and 43 in patients who were HBsAg-negative. The highest prevalence (41%) was among multi-transfused patients according to studies that report occult hepatitis B virus prevalence in an HBsAg-negative population, while the pooled prevalence of OBI among patients on hemodialysis, patients with chronic hepatitis C infection, patients with hepatocellular carcinoma (HCC), and patients with liver cirrhosis was 17%, 10%, 24%, and 13%, respectively. On the other hand, among studies that report OBI prevalence in HBsAg-negative and anti-HBc-positive individuals, the pooled prevalence of OBI among blood donors, patients with chronic hepatitis C infection, and patients with HCC was 12%, 15%, and 31%, respectively. Also, the majority of studies examining the genetic background of OBI have found that genotype D is the most prevalent.
CONCLUSION
This study highlights the high prevalence in OBI among blood donors and high-risk populations in Egypt. The implementation of HBV nucleic acid amplification testing (NAT) may increase the safety of blood transfusions by excluding all HBV DNA-positive donations. However, the cost-effectiveness of these tests should be investigated.
PubMed: 37491501
DOI: 10.1186/s42506-023-00138-4 -
Molecular Psychiatry Jul 2023Epigenetic mechanisms, such as DNA methylation (DNAm), have gained increasing attention as potential biomarkers and mechanisms underlying risk for neurodevelopmental,...
Epigenetic mechanisms, such as DNA methylation (DNAm), have gained increasing attention as potential biomarkers and mechanisms underlying risk for neurodevelopmental, psychiatric and other brain-based disorders. Yet, surprisingly little is known about the extent to which DNAm is linked to individual differences in the brain itself, and how these associations may unfold across development - a time of life when many of these disorders emerge. Here, we systematically review evidence from the nascent field of Neuroimaging Epigenetics, combining structural or functional neuroimaging measures with DNAm, and the extent to which the developmental period (birth to adolescence) is represented in these studies. We identified 111 articles published between 2011-2021, out of which only a minority (21%) included samples under 18 years of age. Most studies were cross-sectional (85%), employed a candidate-gene approach (67%), and examined DNAm-brain associations in the context of health and behavioral outcomes (75%). Nearly half incorporated genetic data, and a fourth investigated environmental influences. Overall, studies support a link between peripheral DNAm and brain imaging measures, but there is little consistency in specific findings and it remains unclear whether DNAm markers present a cause, correlate or consequence of brain alterations. Overall, there is large heterogeneity in sample characteristics, peripheral tissue and brain outcome examined as well as the methods used. Sample sizes were generally low to moderate (median n = 98, n = 80), and attempts at replication or meta-analysis were rare. Based on the strengths and weaknesses of existing studies, we propose three recommendations on how advance the field of Neuroimaging Epigenetics. We advocate for: (1) a greater focus on developmentally oriented research (i.e. pre-birth to adolescence); (2) the analysis of large, prospective, pediatric cohorts with repeated measures of DNAm and imaging to assess directionality; and (3) collaborative, interdisciplinary science to identify robust signals, triangulate findings and enhance translational potential.
Topics: Adolescent; Child; Humans; Brain; DNA Methylation; Epigenesis, Genetic; Neuroimaging; Prospective Studies
PubMed: 37185958
DOI: 10.1038/s41380-023-02067-2 -
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 -
Gastroenterology Research and Practice 2016The relative efficacy of different strategies for chronic hepatitis B (CHB) patients with lamivudine resistance (LAM-R) has not yet been systematically studied. Clinical... (Review)
Review
The relative efficacy of different strategies for chronic hepatitis B (CHB) patients with lamivudine resistance (LAM-R) has not yet been systematically studied. Clinical trials were searched in PUBMED, MEDLINE, EMBASE, and CNKI databases up to February 15, 2016. Nine trials including 764 patients met the entry criteria. In direct meta-analysis, TDF showed a stronger antiviral effect than any one of ETV, LAM/ADV, and ADV against LAM-R hepatitis B virus. LAM/ADV therapy was superior to ADV in suppressing viral replication. ETV achieved similar rate of HBV DNA undetectable compared to ADV or LAM/ADV. In network meta-analysis, TDF had higher rates of HBV DNA undetectable compared to ETV (OR, 24.69; 95% CrI: 5.36-113.66), ADV (OR, 37.28; 95% CrI: 9.73-142.92), or LAM/ADV (OR, 21.05; 95% CrI: 5.70-77.80). However, among ETV, ADV, and LAM/ADV, no drug was clearly superior to others in HBV DNA undetectable rate. Moreover, no significant difference in the rate of ALT normalization or HBeAg loss was observed compared the four rescue strategies with each other. TDF appears to be a more effective rescue therapy than LAM/ADV, ETV, or ADV. LAM plus ADV therapy was a better treatment option than ETV or ADV alone for patients with LAM-R.
PubMed: 27672391
DOI: 10.1155/2016/3435965 -
Psychoneuroendocrinology May 2019The objective of the present study is to synthesize the existing empirical literature and perform a meta-analysis of published data on the relationship between cortisol... (Meta-Analysis)
Meta-Analysis
The objective of the present study is to synthesize the existing empirical literature and perform a meta-analysis of published data on the relationship between cortisol and telomere length. We systematically searched studies that examined the relationship between cortisol and telomere length in humans on electronic databases and screened reference sections of included articles. Fourteen studies were included in the meta-analysis, with effect sizes being extracted for two cortisol measures: basal cortisol levels and cortisol reactivity to acute psychological stress. Results from random effects models showed that basal cortisol levels (13 effect sizes from 12 cross-sectional studies, N = 3675 participants) were not significantly correlated with telomere length (r =-0.05, 95% CI [-0.11, 0.02]). Further, results stratified by the specimen type for cortisol measurement (i.e., saliva, urine, blood) showed that none of the three basal cortisol level measures were correlated with telomere length. However, we found a statistically significant correlation between salivary cortisol reactivity to acute psychosocial stress (6 cross-sectional studies, N = 958 participants) and telomere length (r = -0.13, 95% CI [-0.23, -0.03]). Subgroup analyses revealed that correlations between salivary cortisol reactivity and telomere length were more evident in studies conducted among children (vs. adults) and in studies that included female participants only (vs. both genders). However, the small number of available studies limits the conclusions derived from subgroup analyses, and more studies are needed before moderator effects can be properly established. Overall, findings of this study support the existence of a relationship between cortisol reactivity and telomere shortening.
Topics: Adolescent; Adult; Child; Cross-Sectional Studies; Female; Humans; Hydrocortisone; Male; Middle Aged; Stress, Psychological; Telomere; Telomere Homeostasis; Telomere Shortening
PubMed: 30695740
DOI: 10.1016/j.psyneuen.2019.01.022 -
Bladder Cancer (Amsterdam, Netherlands) Apr 2018The variant/gene candidate approach to explore bladder cancer (BC) genetic susceptibility has been applied in many studies with significant findings reported. However,...
BACKGROUND
The variant/gene candidate approach to explore bladder cancer (BC) genetic susceptibility has been applied in many studies with significant findings reported. However, results are not always conclusive due to the lack of replication by subsequent studies.
OBJECTIVES
To identify all epidemiological investigations on the genetic associations with BC risk, to quantify the likely magnitude of the associations by applying metaanalysis methodology and to assess whether there is a potential for publication/reporting bias.
METHODS
To address our aims, we have catalogued all genetic association studies published in the field of BC risk since 2000. Furthermore, we metaanalysed all polymorphisms with data available from at least three independent case-control studies with subjects of Caucasian origin analyzed under the same mode of inheritance.
RESULTS
The characterization of the genetic susceptibility of BC is composed of 28 variants, GWAS contributing most of them. Most of the significant variants associated with BC risk are located in genes belonging to chemical carcinogenesis, DNA repair, and cell cycle pathways. Causal relationship was also provided by functional analysis for rs1014971, -rs8102137, -rs10775480, -rs2294008, -rs1189203, and -rs35592567.
CONCLUSIONS
Genetic susceptibility of BC is still poorly defined, with GWAS contributing most of the strongest evidence. The systematic review did not provide evidence of further genetic associations. The potential public health translation of the existing knowledge on genetic susceptibility on BC is still limited.
PubMed: 29732392
DOI: 10.3233/BLC-170159 -
Environmental Research Apr 2024Ambient PM exposure has been recognized as a major health risk and related to aging, cardiovascular, respiratory and neurologic diseases, and cancer. However, underlying...
Ambient PM exposure has been recognized as a major health risk and related to aging, cardiovascular, respiratory and neurologic diseases, and cancer. However, underlying mechanism of epigenetic alteration and regulated pathways still remained unclear. The study on methylome effect of PM exposure was quite limited in Chinese population, and cohort-based study was absent. The study included blood-derived DNA methylation for 3365 Chinese participants from the NSPT cohort. We estimated individual PM exposure level of short-medium-, medium- and long-term, based on a validated prediction model. We preformed epigenome-wide association studies to estimate the links between PM exposure and DNA methylation change, as well as stratification and sensitive analysis to examined the robustness of the association models. A systematic review was conducted to obtain the previously published CpGs and examined for replication. We also conducted comparison on the DNA methylation variation corresponding to different time windows. We further conducted gene function analysis and pathway enrichment analysis to reveal related biological response. We identified a total of 177 CpGs and 107 DMRs associated with short-medium-term PM exposure, at a strict genome-wide significance (P < 5 × 10). The effect sizes on most CpGs tended to cease with the exposure of extended time scale. Associated markers and aligned genes were related to aging, immunity, inflammation and carcinogenesis. Enriched pathways were mostly involved in cell cycle and cell division, signal transduction, inflammatory pathway. Our study is the first EWAS on PM exposure conducted in large-scale Han Chinese cohort and identified associated DNA methylation change on CpGs and regions, as well as related gene functions and pathways.
Topics: Humans; Air Pollutants; Particulate Matter; Epigenome; DNA Methylation; China
PubMed: 38246299
DOI: 10.1016/j.envres.2024.118276