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The World Journal of Men's Health Sep 2023The () gene is a paternally expressed imprinted gene that appears to play a role in embryo survival. The latest meta-analysis on methylation pattern in spermatozoa of...
PURPOSE
The () gene is a paternally expressed imprinted gene that appears to play a role in embryo survival. The latest meta-analysis on methylation pattern in spermatozoa of infertile patients found higher methylation in spermatozoa from infertile patients than fertile controls. To provide an updated and comprehensive systematic review and meta-analysis on the gene methylation pattern in patients with abnormal sperm parameters compared to men with normal parameters.
MATERIALS AND METHODS
This meta-analysis was registered in PROSPERO (CRD42023397056) and performed following the MOOSE guidelines for Meta-analyses and Systematic Reviews of Observational Studies and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P). Only original articles evaluating gene methylation in spermatozoa from patients with infertility or abnormalities in one or more sperm parameters compared to fertile or normozoospermic men were included.
RESULTS
Of 354 abstracts evaluated for eligibility, only 6 studies were included in the quantitative synthesis, involving a total of 301 patients and 163 controls. Our analysis showed significantly higher levels of gene methylation in patients compared with controls (standard mean difference [SMD] 2.150, 95% confidence interval [CI] 0.377, 3.922; p=0.017), although there was significant heterogeneity between studies (Q-value=239.90, p<0.001; I²=97.91%). No significant evidence of publication bias was found, although one study was sensitive enough to skew the results, leading to a loss of significance (SMD 1.543, 95% CI -0.300, 3.387; p=0.101). In meta-regression analysis, we found that the results were independent of both ages (p=0.6519) and sperm concentration (p=0.2360).
CONCLUSIONS
Sperm DNA methylation may be associated with epigenetic risk in assisted reproductive techniques (ART). The gene could be included in the genetic panel of prospective studies aimed at identifying the most representative and cost-effective genes to be analyzed in couples undergoing ART.
PubMed: 37853535
DOI: 10.5534/wjmh.230094 -
Frontiers in Oncology 2023The canonical Wnt inhibitor Dickkopf-1 (Dkk-1) has the capacity to modulate homeostasis between canonical and non-canonical Wnt pathways and also signal independently of...
BACKGROUND
The canonical Wnt inhibitor Dickkopf-1 (Dkk-1) has the capacity to modulate homeostasis between canonical and non-canonical Wnt pathways and also signal independently of Wnt. The specific effects of Dkk-1 activity on tumor physiology are therefore unpredictable with examples of Dkk-1 serving as either a driver or suppressor of malignancy. Given that Dkk-1 blockade may serve as a potential treatment for some types of cancer, we questioned whether it is possible to predict the role of Dkk-1 on tumor progression based on the tissue origin of the tumor.
METHODS
Original research articles that described Dkk-1 in terms a tumor suppressor or driver of cancer growth were identified. To determine the association between tumor developmental origin and the role of Dkk-1, a logistic regression was performed. The Cancer Genome Atlas database was interrogated for survival statistics based on tumor Dkk-1 expression.
RESULTS
We report that Dkk-1 is statistically more likely to serve as a suppressor in tumors arising from the ectoderm ( = 0.0198) or endoderm ( = 0.0334) but more likely to serve as a disease driver in tumors of mesodermal origin ( = 0.0155). Survival analyses indicated that in cases where Dkk-1 expression could be stratified, high Dkk-1 expression is usually associated with poor prognosis. This in part may be due to pro-tumorigenic role Dkk-1 plays on tumor cells but also through its influence on immunomodulatory and angiogenic processes in the tumor stroma.
CONCLUSION
Dkk-1 has a context-specific dual role as a tumor suppressor or driver. Dkk-1 is significantly more likely to serve as a tumor suppressor in tumors arising from ectoderm and endoderm while the converse is true for mesodermal tumors. Patient survival data indicated high Dkk-1 expression is generally a poor prognostic indicator. These findings provide further support for the importance of Dkk-1 as a therapeutic cancer target in some cases.
PubMed: 37007131
DOI: 10.3389/fonc.2023.1114822 -
Neuro-degenerative Diseases 2022Several studies indicate the role of mesenchymal stem cells (MSCs) as an important tool in regenerative medicine associated with injuries that affect the central nervous...
INTRODUCTION
Several studies indicate the role of mesenchymal stem cells (MSCs) as an important tool in regenerative medicine associated with injuries that affect the central nervous system (CNS). The MSCs have the capacity to differentiate into cells of the embryonic tissue, such as the mesoderm. So, these cells can be found in a variety of tissues. Also, the MSCs can release immunomodulatory and neurotrophic factors performance as inflammation mediators operating in injured tissue regeneration. Furthermore, they can differentiate into neural-like cells in vitro. Thereby, because of the high immunomodulatory role of MSCs, this review sought to describe the main immunomodulatory mechanisms performed by MSCs in CNS recovery after tissue injury or neurodegenerative diseases.
METHODS
PubMed and ScienceDirect were searched between January 2011 to March 2021, and 43 articles met the criteria of the review.
RESULTS
This systematic review indicates that MSCs were used in vivo experimental multiple sclerosis, Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis, ischemic stroke, and traumatic brain injury. The treatment MSCs were usually from human origin, derived from bone marrow, and administered intravenously.
CONCLUSION
It was shown that MSCs, independent from origin or administration pathway, can reduce inflammation and help in the recovery and preservation of injured neural tissue. Thus, the use of MSCs represents a potential therapeutic option in the treatment of neurological disorders mediated by inflammatory processes.
Topics: Humans; Mesenchymal Stem Cells; Neurodegenerative Diseases; Central Nervous System; Multiple Sclerosis; Parkinson Disease
PubMed: 36398461
DOI: 10.1159/000528036 -
Journal of Ovarian Research Sep 2022Ovarian malignant mesoderm mixed tumor (OMMMT) is a rare clinical entity. To provide reference for the treatment and prognosis of OMMMT, we analyzed the clinical... (Review)
Review
BACKGROUND
Ovarian malignant mesoderm mixed tumor (OMMMT) is a rare clinical entity. To provide reference for the treatment and prognosis of OMMMT, we analyzed the clinical features, pathology and molecular biology characteristic of published cases.
METHODS
The English and Chinese reported cases of OMMMT were selected from PubMed, Clinical Trials.gov and CNKI database from 2000 to December 15th, 2021 following the PRISMA guidelines.
RESULTS
A total of 63 literatures including 199 OMMMT cases were included. The average age of patients at diagnosis was 56.46 years, the highest incidence age was 60-65 years, and 82% of them were menopausal women. Most patients were diagnosed in FIGO III stage (59.64%). The most common symptom of OMMMT was abdominal pain (60.5%). 61.6% of patients were accompanied by ascites, while ascites was not associated with metastatic tumor and local recurrence. The CA125 of 88.68% patients increased. The most common reported carcinomatous component and sarcomatous component were serous adenocarcinoma (44.96%) and chondrosarcoma (24.81%), respectively. Initial treatment included surgery (94.97%) and taxanes-based (55.10%) or platinum-based (85.71%) chemotherapy regimens. The median survival time of patients was 20 months. Heterologous sarcoma component did not shorten life expectancy. The optimal ovarian tumor cell debulking surgery (OOTCDS), radiotherapy and chemotherapy could significantly prolong the median survival time of patients. Furthermore, platinum drugs could significantly prolong the survival time after comparing various chemotherapy schemes. Besides, the combination of platinum and taxanes was therapeutically superior to the combination of platinum and biological alkylating agents.
CONCLUSION
The OOTCDS and platinum-based chemotherapy regimen can improve the prognosis of OMMMT. Targeted therapy might become a new research direction in the future. Since the elderly patients are the majority, the toxicity of new drugs on the elderly patients is more noteworthy.
Topics: Aged; Alkylating Agents; Carcinoma; Female; Humans; Mesoderm; Middle Aged; Ovarian Neoplasms; Taxoids
PubMed: 36114551
DOI: 10.1186/s13048-022-01037-6 -
Journal of Drug Targeting Jan 2023Tissue engineering (TE) has become a new effective solution to a variety of medical problems, including diabetes. Mesenchymal stem cells (MSCs), which have the ability...
Tissue engineering (TE) has become a new effective solution to a variety of medical problems, including diabetes. Mesenchymal stem cells (MSCs), which have the ability to differentiate into endodermal and mesodermal cells, appear to be appropriate for this function. The purpose of this review was to evaluate the outcomes of various researches on the insulin-producing cells (IPCs) generation from MSCs with TE approaches to increase efficacy of type 1 diabetes treatments. The search was performed in PubMed/Medline, Scopus and Embase databases until 2021. Studies revealed that MSCs could also differentiate into IPCs under certain conditions. Therefore, a wide range of protocols have been used for this differentiation, but their effectiveness is very different. Scaffolds can provide a microenvironment that enhances the MSCs to IPCs differentiation, improves their metabolic activity and up-regulate pancreatic-specific transcription factors. They also preserve IPCs architecture and enhance insulin production as well as protect against cell death. This systematic review offers a framework for prospective research based on data. and evidence suggests that scaffold-based TE can improve the viability and function of IPCs.
Topics: Humans; Diabetes Mellitus, Type 1; Tissue Engineering; Prospective Studies; Cell Differentiation; Insulin
PubMed: 35896313
DOI: 10.1080/1061186X.2022.2107653 -
Human Reproduction Update Aug 2022The many manipulations and processes used in ART coincide with the timing of epigenetic reprogramming and imprinting during female gametogenesis and pre-implantation... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The many manipulations and processes used in ART coincide with the timing of epigenetic reprogramming and imprinting during female gametogenesis and pre-implantation embryo development, leading to concerns that the actual ART could negatively affect epigenetic reprogramming and imprinting in gametes and early embryos. A growing body of literature suggests that ART may affect epigenetic marks, such as DNA methylation, in the fetus and placenta. Potentially, this may be responsible later in life for the increased risk of adverse outcomes associated with ART. Unfortunately, the conclusions are inconsistent and, despite the increasing usage of ART, its safety at the epigenetic level is still not established.
OBJECTIVE AND RATIONALE
To examine whether ART is associated with DNA methylation modifications and if these modifications persist throughout life, we provide an update on the current understanding of epigenetic reprogramming in human gametes and embryos, and then focus on the assessment of fetal and postnatal DNA methylation modifications that may remain until adulthood following the use of ART in humans.
SEARCH METHODS
We reviewed studies using targeted or epigenome-wide techniques to assess the DNA methylation patterns of the conceptus after ART compared with natural conceptions. A search for relevant studies was performed in the PubMed and EMBASE databases on 15 July 2021 with an extensive search equation. Studies on animals, gametes and embryos were subsequently excluded. After an in-depth review of full-text articles, studies on specific populations with imprinting disorders were removed and not further discussed. Before comprehensive analysis, the risk of bias of each included study was assessed with the Newcastle-Ottawa scale and quality of evidence was graded using the Grading of Recommendations, Assessment, Development and Evaluations criteria.
OUTCOMES
In total, 928 records were initially identified, and 51 were finally included in the systematic review. Given the variability in the genomic scale at which DNA methylation was measured in the different studies, they were separated into two categories: targeted DNA methylation or genome-wide DNA methylation study. The present systematic review has made it possible to assess a substantial number of children since more than 4000 DNA methylation profiles of ART concepti were compared to more than 7000 controls. There is evidence that ART conception is associated with aberrant DNA methylation in imprinted loci and other genes in various tissues. One isolated modification notably occur in the paternally expressed gene 1/mesoderm-specific transcript homologue (PEG1/MEST) region, and we cannot rule out other studied sequences owing to the heterogeneity of the evidence base.
WIDER IMPLICATIONS
Differences in DNA methylation after ART conceptions are modest, and the functional relevance in adult tissues is unknown. Functional effects in terms of gene expression as well as the roles of other epigenetic marks need to be further explored. Moreover, there is little overlap of findings obtained in targeted and genome-scale analyses owing to the lack of comparability of CpGs analyzed between both techniques. This issue also stems from small sample sizes and marked differences in methodology and cohort characteristics. Standardization of methodologies and large collaborative efforts are required to reduce the inconsistency of results and increase the robustness of findings. Finally, further studies are required to determine the contribution of parental infertility per se from the ART treatment.
Topics: Adult; Animals; Child; DNA; DNA Methylation; Female; Fertilization in Vitro; Genomic Imprinting; Humans; Infertility; Longevity; Pregnancy
PubMed: 35259267
DOI: 10.1093/humupd/dmac010 -
Head and Neck Pathology Dec 2020The microenvironment of oral cancer is highly dynamic and has been proved to affect tumor progression. Pericytes are blood vessels surrounding cells that have recently...
The microenvironment of oral cancer is highly dynamic and has been proved to affect tumor progression. Pericytes are blood vessels surrounding cells that have recently gained attention for their roles in vascular and cancer biology. The objective of the present study was to survey the scientific literature for conclusive evidence about whether pericytes are part of blood vessels in oral squamous cell carcinoma (OSCC) and their roles in the tumor microenvironment and clinical outcomes. A systematic electronic search was undertaken in Medline Ovid, PubMed, Web of Science, and Scopus. Eligibility criteria were: publications adopting in vivo models of OSCC that included pericyte detection and assessment by pericyte markers (e.g., α-smooth muscle actin, neuron-glial antigen 2 and platelet-derived growth factor receptor-β). The search yielded seven eligible studies (from 2008 to 2018). The markers most commonly used for pericyte detection were α-smooth muscle actin and neuron-glial antigen 2. The studies reviewed showed the presence of immature vessels exhibiting a reduction of pericyte coverage in OSCC and indicated that anti-cancer therapies could contribute to vessel normalization and pericyte regain. The pericyte population is significantly affected during OSCC development and cancer therapy. While these findings might suggest a role for pericytes in OSCC progression, the limited data available do not allow us to conclude whether they modify the tumor microenvironment and clinical outcome.
Topics: Animals; Humans; Mouth Neoplasms; Pericytes; Squamous Cell Carcinoma of Head and Neck; Tumor Microenvironment
PubMed: 32506378
DOI: 10.1007/s12105-020-01188-2 -
Tissue Engineering. Part B, Reviews Aug 2020Human Wharton's jelly stem cells (HWJSC) can be efficiently isolated from the umbilical cord, and numerous reports have demonstrated that these cells can differentiate...
Human Wharton's jelly stem cells (HWJSC) can be efficiently isolated from the umbilical cord, and numerous reports have demonstrated that these cells can differentiate into several cell lineages. This fact, coupled with the high proliferation potential of HWJSC, makes them a promising source of stem cells for use in tissue engineering and regenerative medicine. However, their real potentiality has not been established to date. In the present study, we carried out a systematic review to determine the multilineage differentiation potential of HWJSC. After a systematic literature search, we selected 32 publications focused on the differentiation potential of these cells. Analysis of these studies showed that HWJSC display expanded differentiation potential toward some cell types corresponding to all three embryonic cell layers (ectodermal, mesodermal, and endodermal), which is consistent with their constitutive expression of key pluripotency markers such as OCT4, SOX2, and NANOG, and the embryonic marker SSEA4. We conclude that HWJSC can be considered cells in an intermediate state between multipotentiality and pluripotentiality, since their proliferation capability is not unlimited and differentiation to all cell types has not been demonstrated thus far. These findings support the clinical use of HWJSC for the treatment of diseases affecting not only mesoderm-type tissues but also other cell lineages. Impact statement Human Wharton's jelly stem cells (HWJSC) are mesenchymal stem cells that are easy to isolate and handle, and that readily proliferate. Their wide range of differentiation capabilities supports the view that these cells can be considered pluripotent. Accordingly, HWJSC are one of the most promising cell sources for clinical applications in advanced therapies.
Topics: Cell Differentiation; Cell Lineage; Humans; Mesenchymal Stem Cells; Pluripotent Stem Cells; Regenerative Medicine; Stem Cells
PubMed: 32085697
DOI: 10.1089/ten.TEB.2019.0257 -
International Journal of Environmental... Dec 2019Physical, chemical, and social environments adversely affect the molecular process and results in cell signal transduction and the subsequent transcription factor...
DNA Methylation of Candidate Genes (ACE II, IFN-γ, AGTR 1, CKG, ADD1, SCNN1B and TLR2) in Essential Hypertension: A Systematic Review and Quantitative Evidence Synthesis.
Physical, chemical, and social environments adversely affect the molecular process and results in cell signal transduction and the subsequent transcription factor dysregulation, leading to impaired gene expression and abnormal protein synthesis. Stressful environments such as social adversity, isolation, sustained social threats, physical inactivity, and highly methylated diets predispose individuals to molecular level alterations such as aberrant epigenomic modulations that affect homeostasis and hemodynamics. With cardiovascular disease as the leading cause of mortality in the US and blacks/African Americans being disproportionately affected by hypertension (HTN) which contributes substantially to these deaths, reflecting the excess mortality and survival disadvantage of this sub-population relative to whites, understanding the molecular events, including epigenomic and socio-epigenomic modulations, is relevant to narrowing the black-white mortality risk differences. We aimed to synthesize epigenomic findings in HTN namely (a) angiotensin-converting enzyme 2 (ACE II) gene, (b) Toll-like receptor 2 (TLR2) gene, (c) interferon γ (IFN-γ) gene, and (d) Capping Actin Protein, Gelosin-Like () , adducin 1(ADD1) gene, (e) Tissue inhibitor of metalloproteinase 3 (), (f) mesoderm specific transcript (MEST) loci, (g) sodium channel epithelial 1 alpha subunit 2 (SCNN1B), (h) glucokinase (CKG) gene (i) angiotensin II receptor, type1 (AGTR1), and DNA methylation (mDNA). A systematic review and quantitative evidence synthesis (QES) was conducted using Google Scholar and PubMed with relevant search terms. Data were extracted from studies on: (a) Epigenomic modulations in HTN based on ACE II (b) TLR2, (c) IFN-γ gene, (d) , ADD1, , MEST loci, and mDNA. The random-effect meta-analysis method was used for a pooled estimate of the common effect size, while z statistic and I^2 were used for the homogeneity of the common effect size and between studies on heterogeneity respectively. Of the 642 studies identified, five examined hypermethylation while seven studies assessed hypomethylation in association with HTN. The hypermethylation of ACE II, SCNN1B, CKG, IFN-γ gene, and miR-510 promoter were associated with hypertension, the common effect size (CES) = 6.0%, 95% CI, -0.002-11.26. In addition, the hypomethylation of TLR2, IFN-γ gene, ADD1, AGTR1, and GCK correlated with hypertension, the CES = 2.3%, 95% CI, -2.51-7.07. The aberrant epigenomic modulation of ACE II, TLR2, IFN-γ, AGTR1, and GCK correlated with essential HTN. Transforming the environments resulting from these epigenomic lesions will facilitate early intervention mapping in reducing HTN in the US population, especially among socially disadvantaged individuals, particularly racial/ethnic minorities.
Topics: DNA Methylation; Essential Hypertension; Female; Genotype; Humans
PubMed: 31805646
DOI: 10.3390/ijerph16234829 -
The American Journal of Dermatopathology Sep 2020Goltz-Gorlin syndrome (GGS) (focal dermal hypoplasia) is a very rare developmental disorder affecting ectodermal and mesodermal structures. The syndrome is inherited in...
Goltz-Gorlin syndrome (GGS) (focal dermal hypoplasia) is a very rare developmental disorder affecting ectodermal and mesodermal structures. The syndrome is inherited in an X-linked manner, with the majority of affected individuals being female. We report the case of a 51-year-old man presenting with congenital skin lesions, syndactyly, facial and thoracic asymmetry, inguinal and laryngeal papillomas, cryptorchidism, polythelia, and dental anomalies. Molecular genetic analysis confirmed the clinically suspected diagnosis of GGS by detecting a known pathogenic mutation in the PORCN gene, c.502G>A [p.(Gly168Arg)] in the mosaic state. Histopathological examinations of skin biopsies of affected individuals typically show focal dermal hypoplasia and fat herniation; despite numerous skin biopsies, these characteristics were not found in the patient involved. Instead, we observed a notable reduction and fragmentation of the elastic fibers in the upper dermis. A systematic literature review regarding the histopathological presence or absence of dermal hypoplasia and/or information on elastic fibers revealed 240 histopathological descriptions of 173 individuals. Absence of dermal hypoplasia was found in 21 biopsies (8.8%). Information on elastic fibers was given in 47 cases (19.6%), showing decrease/absence in 31 cases and fragmentation of elastic fibers in 11 cases. Therefore, the histopathological absence of dermal hypoplasia does not exclude the diagnosis of the GGS. Decrease and fragmentation of elastic fibers may represent new histopathological clues to the diagnosis of this rare syndrome. At the same time, GGS should be included in the histopathological differential diagnoses of elastolytic disorders.
Topics: Acyltransferases; Adolescent; Adult; Aged; Biopsy; Child; Child, Preschool; DNA Mutational Analysis; Dermis; Diagnosis, Differential; Elastic Tissue; Female; Focal Dermal Hypoplasia; Genetic Predisposition to Disease; Humans; Infant; Male; Membrane Proteins; Middle Aged; Mutation; Phenotype; Predictive Value of Tests; Young Adult
PubMed: 31789838
DOI: 10.1097/DAD.0000000000001579