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Frontiers in Neuroendocrinology Apr 2022Adverse childhood experiences (ACEs) may leave long-lasting neurobiological scars, increasing the risk of developing mental disorders in later life. However, no review... (Review)
Review
Adverse childhood experiences (ACEs) may leave long-lasting neurobiological scars, increasing the risk of developing mental disorders in later life. However, no review has comprehensively integrated existing evidence across the fields: hypothalamic-pituitary-adrenal axis, immune/inflammatory system, neuroimaging, and genetics/epigenetics. We thus systematically reviewed previous meta-analyses towards an integrative account of ACE-related neurobiological alterations. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline, a total of 27 meta-analyses until October 2021 were identified. This review found that individuals with ACEs possess blunted cortisol response to psychosocial stressors, low-grade inflammation evinced by increased C-reactive protein levels, exaggerated amygdalar response to emotionally negative information, and diminished hippocampal gray matter volume. Importantly, these alterations were consistently observed in those with and without psychiatric diagnosis. These findings were integrated and discussed in a schematic model of ACE-related neurobiological alterations. Future longitudinal research based on multidisciplinary approach is imperative for ACE-related mental disorders' prevention and treatment.
Topics: Adverse Childhood Experiences; Humans; Hypothalamo-Hypophyseal System; Mental Disorders; Pituitary-Adrenal System; Stress, Psychological
PubMed: 35331780
DOI: 10.1016/j.yfrne.2022.100994 -
Molecular Neurodegeneration Mar 2022Alzheimer's disease (AD) is the most common form of dementia, characterized by progressive cognitive impairment and neurodegeneration. Extensive clinical and genomic... (Review)
Review
Alzheimer's disease (AD) is the most common form of dementia, characterized by progressive cognitive impairment and neurodegeneration. Extensive clinical and genomic studies have revealed biomarkers, risk factors, pathways, and targets of AD in the past decade. However, the exact molecular basis of AD development and progression remains elusive. The emerging single-cell sequencing technology can potentially provide cell-level insights into the disease. Here we systematically review the state-of-the-art bioinformatics approaches to analyze single-cell sequencing data and their applications to AD in 14 major directions, including 1) quality control and normalization, 2) dimension reduction and feature extraction, 3) cell clustering analysis, 4) cell type inference and annotation, 5) differential expression, 6) trajectory inference, 7) copy number variation analysis, 8) integration of single-cell multi-omics, 9) epigenomic analysis, 10) gene network inference, 11) prioritization of cell subpopulations, 12) integrative analysis of human and mouse sc-RNA-seq data, 13) spatial transcriptomics, and 14) comparison of single cell AD mouse model studies and single cell human AD studies. We also address challenges in using human postmortem and mouse tissues and outline future developments in single cell sequencing data analysis. Importantly, we have implemented our recommended workflow for each major analytic direction and applied them to a large single nucleus RNA-sequencing (snRNA-seq) dataset in AD. Key analytic results are reported while the scripts and the data are shared with the research community through GitHub. In summary, this comprehensive review provides insights into various approaches to analyze single cell sequencing data and offers specific guidelines for study design and a variety of analytic directions. The review and the accompanied software tools will serve as a valuable resource for studying cellular and molecular mechanisms of AD, other diseases, or biological systems at the single cell level.
Topics: Alzheimer Disease; Animals; Computational Biology; DNA Copy Number Variations; Data Analysis; Mice; Single-Cell Analysis
PubMed: 35236372
DOI: 10.1186/s13024-022-00517-z -
International Journal of Molecular... Dec 2021Penile squamous cell carcinoma (PSCC) is a rare but aggressive neoplasm with dual pathogenesis (human papillomavirus (HPV)-associated and HPV-independent). The...
Penile squamous cell carcinoma (PSCC) is a rare but aggressive neoplasm with dual pathogenesis (human papillomavirus (HPV)-associated and HPV-independent). The development of targeted treatment is hindered by poor knowledge of the molecular landscape of PSCC. We performed a thorough review of genetic alterations of PSCC focused on somatic mutations and/or copy number alterations. A total of seven articles have been identified which, overall, include 268 PSCC. However, the series are heterogeneous regarding methodologies employed for DNA sequencing and HPV detection together with HPV prevalence, and include, in general, a limited number of cases, which results in markedly different findings. Reported top-ranked mutations involve , , , and . Numerical alterations involve gains in and , as well as amplifications in HPV integration loci. A few genes including , , and harbor both somatic mutations and copy number alterations. Notch, RTK-RAS and Hippo pathways are frequently deregulated. Nevertheless, the relevance of the identified alterations, their role in signaling pathways or their association with HPV status remain elusive. Combined targeting of different pathways might represent a valid therapeutic approach in PSCC. This work calls for large-scale sequencing studies with robust HPV testing to improve the genomic understanding of PSCC.
Topics: Carcinoma, Squamous Cell; DNA Copy Number Variations; Geography; Humans; Male; Molecular Targeted Therapy; Mutation; Papillomaviridae; Penile Neoplasms; Prognosis; Signal Transduction
PubMed: 35008677
DOI: 10.3390/ijms23010251 -
Antioxidants (Basel, Switzerland) Dec 2021Physical activity may benefit health by modulating oxidative stress and inflammation. However, the selection of suitable exercise-induced oxidative stress biomarkers is... (Review)
Review
Physical activity may benefit health by modulating oxidative stress and inflammation. However, the selection of suitable exercise-induced oxidative stress biomarkers is still challenging. This study aimed at systematically summarizing the available evidence on exercise-induced oxidative stress measured in urine and/or saliva. Two meta-analyses including the most frequently quantified biomarkers of oxidative stress, namely, urinary isoprostane and DNA oxidation products, were performed. Three electronic databases (PubMed, EMBASE and Cochrane CENTRAL) were interrogated. Among 4479 records, 43 original articles were included in the systematic review and 11 articles were included in meta-analysis I and II, respectively. We observed a pooled trend of increase of urinary isoprostanes in response to physical activity (+0.95, 95% CI: -0.18; 2.09). In comparison with aerobic exercise, anaerobic training determined a greater induction of isoprostanes (+5.21, 95% CI: 2.76; 7.66, < 0.0001), which were markedly increased after vigorous physical activity (+6.01, 95% CI: 1.18; 10.84, < 0.001) and slightly decreased in response to exercise interventions protracted over time (e.g., months) (-1.19, 95% CI: -2.25; -0.12, < 0.001). We recommend the most integrative approach of oxidative stress multi-marker panels in response to physical activity instead of selecting one preferential biomarker to quantify physical activity-induced oxidative stress in humans.
PubMed: 34943111
DOI: 10.3390/antiox10122008 -
BMC Microbiology Nov 2021Although recent studies have indicated that imbalance in the respiratory microbiome composition is linked to several chronic respiratory diseases, the association... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Although recent studies have indicated that imbalance in the respiratory microbiome composition is linked to several chronic respiratory diseases, the association between the lung microbiome and lung cancer has not been extensively studied. Conflicting reports of individual studies on respiratory microbiome alterations in lung cancer complicate the matter for specifying how the lung microbiome is linked to lung cancer. Consequently, as the first meta-analysis on this topic, we integrate publicly available 16S rRNA gene sequence data on lung tissue samples of lung cancer patients to identify bacterial taxa which differ consistently between case and control groups.
RESULTS
The findings of the current study suggest that the relative abundance of several bacterial taxa including Actinobacteria phylum, Corynebacteriaceae and Halomonadaceae families, and Corynebacterium, Lachnoanaerobaculum, and Halomonas genera is significantly decreased (p < 0.05) in lung tumor tissues of lung cancer patients in comparison with tumor-adjacent normal tissues.
CONCLUSIONS
Despite the underlying need for scrutinizing the findings further, the present study lays the groundwork for future research and adds to our limited understanding of the key role of the lung microbiome and its complex interaction with lung cancer. More data on demographic factors and tumor tissue types would help establish a greater degree of accuracy in characterizing the lung microbial community which accords with subtypes and stages of the disease and fully capturing the changes of the lung microbiome in lung cancer.
Topics: Adult; Aged; Aged, 80 and over; Bacteria; DNA, Bacterial; Female; Humans; Lung; Lung Neoplasms; Male; Microbiota; RNA, Ribosomal, 16S
PubMed: 34763672
DOI: 10.1186/s12866-021-02375-z -
Frontiers in Pharmacology 2021As lifestyle and diet structure impact our health, non-alcoholic fatty liver disease (NAFLD) is prevalent all over the world. Some phytomedicines containing berberine...
As lifestyle and diet structure impact our health, non-alcoholic fatty liver disease (NAFLD) is prevalent all over the world. Some phytomedicines containing berberine (BBR) have been extensively used for centuries in Ayurvedic and traditional Chinese medicine. The goal of this systematic review is to investigate the preclinical evidence of BBR on NAFLD models. The following relevant databases, including Web of Science, PubMed, the Cochrane Library, and Embase, were retrieved from inception to May 2021. The content involved BBR on different animal models for the treatment of NAFLD. The SYstematic Review Center for Laboratory animal Experimentation (SYRCLE) Animal Experiment Bias Risk Assessment Tool was used to assess the methodological quality and RevMan 5.4 software was used to conduct the meta-analysis based on the Cochrane tool. A total of 31 studies involving 566 animals were included, of which five models and five animal breeds were reported. The results showed that TC, TG, ALT, AST, HDL-C, LDL-C, FBG, FINS, and FFA in the group treated with BBR were significantly restored compared with those in the model group. HOMA-IR had a significant downward trend, but the result was not significantly different (P = 0.08). The subgroup analysis of the different models and different animal breeds indicated that BBR could ameliorate the aforementioned indicator levels, although some results showed no significant difference. Finally, we summarized the molecular mechanisms by which berberine regulated NAFLD/NASH, mainly focusing on activating the AMPK pathway, improving insulin sensitivity and glucose metabolism, regulating mitochondrial function, reducing inflammation and oxidative stress, regulating cell death and ER stress, reducing DNA methylation, and regulating intestinal microenvironment and neurotoxicity. The preclinical evidence suggested that BBR might be an effective and promising drug for treating NAFLD/NASH. In addition, further studies with more well-designed researches are needed to confirm this conclusion.
PubMed: 34566663
DOI: 10.3389/fphar.2021.742465 -
Medicine Aug 2021Plenty of studies have showed matrix metalloproteinase 14 (MMP14) expression might be associated with the prognosis of gastric cancer (GC). However, no definite... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Plenty of studies have showed matrix metalloproteinase 14 (MMP14) expression might be associated with the prognosis of gastric cancer (GC). However, no definite conclusion has been obtained for the contradictory results.
METHODS
We searched PubMed, Web of science, Embase, and Cochrane library for eligible studies. The association between MMP14 expression and prognostic outcomes of GC was evaluated. Hazard ratio (HR) and 95% confidence interval (CI) were integrated to show the effect of MMP14 expression on the overall survival (OS) or recurrence-free survival (RFS). Data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) was used to validate the association of MMP14 expression with OS or RFS in GC. A brief bioinformatics analysis was also performed to determine the prognostic role of MMP14 expression in GC.
RESULTS
High MMP14 expression was associated with shorter OS compared to low MMP14 expression in GC (HR = 1.95, P < .01). Patients with high MMP14 expression tended to have worse differentiation (P = .03), deeper tumor invasion (P < .01), earlier lymph node metastasis (P < .01), earlier distant metastasis (P < .01) and more advanced clinical stage (P < .01) compared to those with low MMP14 expression. The data from TCGA and GEO showed MMP14 was overexpressed in tumor tissues compared to normal tissues (P < .05), and high MMP14 expression was significantly related to shorter OS (HR = 1.70, 95% CI = 1.32-2.20, P < .01) and RFS (HR = 1.45, 95% CI = 1.15-1.83, P < .01) compared to low MMP14 expression in GC. Expression of MMP14 was linked to functional networks involving the biological process, metabolic process, response to stimulus, cell communication and so on. Functional network analysis suggested that MMP14 regulated the protein digestion and absorption, extracellular matrix receptor interaction, focal adhesion, ribosome, spliceosome, and so on.
CONCLUSION
High MMP14 expression was associated with worse prognosis of GC compared to low MMP14 expression. MMP14 expression could serve as a prognostic factor and potential therapeutic target of GC.
Topics: Biomarkers, Tumor; DNA, Neoplasm; Disease Progression; Gene Expression Regulation, Neoplastic; Humans; Matrix Metalloproteinase 14; Prognosis; Stomach Neoplasms
PubMed: 34397871
DOI: 10.1097/MD.0000000000026545 -
International Journal of Molecular... Jul 2021Medical staff represent the largest group of workers occupationally exposed to ionizing radiation (IR). Chronic exposure to low-dose IR may result in DNA damage and... (Meta-Analysis)
Meta-Analysis
Medical staff represent the largest group of workers occupationally exposed to ionizing radiation (IR). Chronic exposure to low-dose IR may result in DNA damage and genotoxicity associated with increased risk of cancer. This review aims to identify the genotoxicity biomarkers that are the most elevated in IR-exposed vs. unexposed health workers. A systematic review of the literature was performed to retrieve relevant studies with various biomarkers of genotoxicity. Subsequent meta-analyses produced a pooled effect size for several endpoints. The search procedure yielded 65 studies. Chromosome aberrations (CA) and micronuclei (MN) frequencies were significantly different between IR-exposed and unexposed workers (θ = 3.19, 95% CI 1.46-4.93; and θ = 1.41, 95% CI 0.97-1.86, for total aberrant cells and MN frequencies, respectively), which was not the case for ring chromosomes and nucleoplasmic bridges. Although less frequently used, stable translocations, sister chromatid exchanges (SCE) and comet assay endpoints were also statistically different between IR-exposed and unexposed workers. This review confirms the relevance of CA and MN as genotoxicity biomarkers that are consistently elevated in IR-exposed vs. unexposed workers. Other endpoints are strong candidates but require further studies to validate their usefulness. The integration of the identified biomarkers in future prospective epidemiological studies is encouraged.
Topics: Biomarkers; Chromosome Aberrations; DNA Damage; Dose-Response Relationship, Radiation; Health Personnel; Humans; Occupational Exposure; Radiation, Ionizing
PubMed: 34299125
DOI: 10.3390/ijms22147504 -
Diseases of the Esophagus : Official... Feb 2022Esophageal cancer is an aggressive malignancy with a relatively poor prognosis even after multimodality therapy. Currently, patients undergo a series of investigations... (Meta-Analysis)
Meta-Analysis
Esophageal cancer is an aggressive malignancy with a relatively poor prognosis even after multimodality therapy. Currently, patients undergo a series of investigations that can be invasive and costly or pose secondary risks to their health. In other malignancies, liquid biopsies of circulating tumor DNA (ctDNA) are used in clinical practice for diagnostic and surveillance purposes. This systematic review summarizes the latest evidence for the clinical applicability of ctDNA technology in esophageal cancer. A systematic review of the literature was performed using MEDLINE, EMBASE, the Cochrane Review and Scopus databases. Articles were evaluated for the use of ctDNA for diagnosis and monitoring of patients with esophageal cancer. Quality assessment of studies was performed using the QUADAS-2 tool. A meta-analysis was performed to assess the diagnostic accuracy of sequencing methodologies. We included 15 studies that described the use of ctDNA technology in the qualitative synthesis and eight studies involving 414 patients in the quantitative analysis. Of these, four studies assessed its utility in cancer diagnosis, while four studies evaluated its use for prognosis and monitoring. The pooled sensitivity and specificity for diagnostic studies were 71.0% (55.7-82.6%) and 98.6% (33.9-99.9%), while the pooled sensitivity and specificity for surveillance purposes were 48.9% (29.4-68.8%) and 95.5% (90.6-97.9%). ctDNA technology is an acceptable method for diagnosis and monitoring with a moderate sensitivity and high specificity that is enhanced in combination with current imaging methods. Further work should demonstrate the practical integration of ctDNA in the diagnostic and surveillance clinical pathway.
Topics: Circulating Tumor DNA; Esophageal Neoplasms; Humans; Prognosis; Sensitivity and Specificity
PubMed: 34286823
DOI: 10.1093/dote/doab046 -
Veterinary Medicine and Science Sep 2021There is an evidence that ginger enhance semen quality via improving different sperm parameters mainly count, viability, motility, morphology and DNA integrity.... (Review)
Review
There is an evidence that ginger enhance semen quality via improving different sperm parameters mainly count, viability, motility, morphology and DNA integrity. According to research results in various species, ginger seems to have strong antioxidant properties (due to the presence of active phenolic compounds) and androgenic activity. Ginger improves semen quality and increases fertility of sperm by disrupting the production of free radicals, dissolving oxidative chain reactions, reducing oxidative stress and altering the levels of gonadotropin hormones (LH, FSH) and sex hormones (such as testosterone). The antioxidant and androgenic properties of ginger give a sperm with normal morphological structure (head, middle and tail) and more integrated chromatin. The rate of DNA failure and damage to the mitochondrial genome in these cells is minimal and they have the most progressive motility, the highest viability and the best fertility. Therefore, the use of the ginger significantly improves the biological parameters of sperm (number, total motility, survival rate and normal morphology) and also increases all specialized fertility indicators of sperm. Tacking account of lacking literature and possibility of toxicity and adverse effect of ginger on vital organ, further clinical trial especially on evaluating the safety and clinical effect must be considered. Also, dose and duration of consumption by monitoring of health indicators and biochemical changes in all species such as human, animal and poultry must be applied.
Topics: Animals; Animals, Laboratory; Fertility; Zingiber officinale; Humans; Poultry; Semen Analysis; Sperm Motility; Spermatozoa
PubMed: 34191404
DOI: 10.1002/vms3.538