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International Journal of Molecular... Jun 2022Alport syndrome (AS) is the second most common cause of inherited chronic kidney disease. This disorder is caused by genetic variants on , and genes. These genes... (Review)
Review
Alport syndrome (AS) is the second most common cause of inherited chronic kidney disease. This disorder is caused by genetic variants on , and genes. These genes encode the proteins that constitute collagen type IV of the glomerular basement membrane (GBM). The heterodimer COL4A3A4A5 constitutes the majority of the GBM, and it is essential for the normal function of the glomerular filtration barrier (GFB). Alterations in any of collagen type IV constituents cause disruption of the GMB structure, allowing leakage of red blood cells and albumin into the urine, and compromise the architecture of the GFB, inducing inflammation and fibrosis, thus resulting in kidney damage and loss of renal function. The advances in DNA sequencing technologies, such as next-generation sequencing, allow an accurate diagnose of AS. Due to the important risk of the development of progressive kidney disease in AS patients, which can be delayed or possibly prevented by timely initiation of therapy, an early diagnosis of this condition is mandatory. Conventional biomarkers such as albuminuria and serum creatinine increase relatively late in AS. A panel of biomarkers that might detect early renal damage, monitor therapy, and reflect the prognosis would have special interest in clinical practice. The aim of this systematic review is to summarize the biomarkers of renal damage in AS as described in the literature. We found that urinary Podocin and Vascular Endothelial Growth Factor A are important markers of podocyte injury. Urinary Epidermal Growth Factor has been related to tubular damage, interstitial fibrosis and rapid progression of the disease. Inflammatory markers such as Transforming Growth Factor Beta 1, High Motility Group Box 1 and Urinary Monocyte Chemoattractant Protein- 1 are also increased in AS and indicate a higher risk of kidney disease progression. Studies suggest that miRNA-21 is elevated when renal damage occurs. Novel techniques, such as proteomics and microRNAs, are promising.
Topics: Biomarkers; Collagen Type IV; Fibrosis; Humans; Kidney; Nephritis, Hereditary; Vascular Endothelial Growth Factor A
PubMed: 35806283
DOI: 10.3390/ijms23137276 -
Placenta Mar 2020Preeclampsia is a medical condition affecting 5-10% of pregnancies. It has serious effects on the health of the pregnant mother and developing fetus. While possible...
Preeclampsia is a medical condition affecting 5-10% of pregnancies. It has serious effects on the health of the pregnant mother and developing fetus. While possible causes of preeclampsia are speculated, there is no consensus on its etiology. The advancement of big data and high-throughput technologies enables to study preeclampsia at the new and systematic level. In this review, we first highlight the recent progress made in the field of preeclampsia research using various omics technology platforms, including epigenetics, genome-wide association studies (GWAS), transcriptomics, proteomics and metabolomics. Next, we integrate the results in individual omic level studies, and show that despite the lack of coherent biomarkers in all omics studies, inhibin is a potential preeclamptic biomarker supported by GWAS, transcriptomics and DNA methylation evidence. Using network analysis on the biomarkers of all the literature reviewed here, we identify four striking sub-networks with clear biological functions supported by previous molecular-biology and clinical observations. In summary, omics integration approach offers the promise to understand molecular mechanisms in preeclampsia.
Topics: Epigenesis, Genetic; Female; Genomics; Humans; Inhibins; Pre-Eclampsia; Pregnancy; Proteome; Transcriptome
PubMed: 32056783
DOI: 10.1016/j.placenta.2020.01.008 -
Gut Aug 2015Data on genetic susceptibility to sporadic gastric carcinoma have been published at a growing pace, but to date no comprehensive overview and quantitative summary has... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Data on genetic susceptibility to sporadic gastric carcinoma have been published at a growing pace, but to date no comprehensive overview and quantitative summary has been available.
METHODS
We conducted a systematic review and meta-analysis of the evidence on the association between DNA variation and risk of developing stomach cancer. To assess result credibility, summary evidence was graded according to the Venice criteria and false positive report probability (FPRP) was calculated to further validate result noteworthiness. Meta-analysis was also conducted for subgroups, which were defined by ethnicity (Asian vs Caucasian), tumour histology (intestinal vs diffuse), tumour site (cardia vs non-cardia) and Helicobacter pylori infection status (positive vs negative).
RESULTS
Literature search identified 824 eligible studies comprising 2 530 706 subjects (cases: 261 386 (10.3%)) and investigating 2841 polymorphisms involving 952 distinct genes. Overall, we performed 456 primary and subgroup meta-analyses on 156 variants involving 101 genes. We identified 11 variants significantly associated with disease risk and assessed to have a high level of summary evidence: MUC1 rs2070803 at 1q22 (diffuse carcinoma subgroup), MTX1 rs2075570 at 1q22 (diffuse), PSCA rs2294008 at 8q24.2 (non-cardia), PRKAA1 rs13361707 5p13 (non-cardia), PLCE1 rs2274223 10q23 (cardia), TGFBR2 rs3087465 3p22 (Asian), PKLR rs3762272 1q22 (diffuse), PSCA rs2976392 (intestinal), GSTP1 rs1695 11q13 (Asian), CASP8 rs3834129 2q33 (mixed) and TNF rs1799724 6p21.3 (mixed), with the first nine variants characterised by a low FPRP. We also identified polymorphisms with lower quality significant associations (n=110).
CONCLUSIONS
We have identified several high-quality biomarkers of gastric cancer susceptibility. These data will form the backbone of an annually updated online resource that will be integral to the study of gastric carcinoma genetics and may inform future screening programmes.
Topics: Gene Frequency; Genetic Predisposition to Disease; Genetic Variation; Genome-Wide Association Study; Humans; Neoplasm Proteins; Polymorphism, Genetic; Risk Factors; Stomach Neoplasms
PubMed: 25731870
DOI: 10.1136/gutjnl-2015-309168 -
Andrology Jan 2024Infertility affects 186 million people worldwide, with male factors contributing to 50% of infertility cases. Semen analysis is a key for diagnosing male factor... (Review)
Review
BACKGROUND
Infertility affects 186 million people worldwide, with male factors contributing to 50% of infertility cases. Semen analysis is a key for diagnosing male factor infertility, but sperm parameters can be influenced by ejaculatory abstinence (EA) duration. Shortening or prolonging EA can impact on semen quality and assisted reproductive technology (ART) outcomes, but the optimal EA duration remains unclear, particularly for infertility patients.
OBJECTIVES
This study conducts a comprehensive meta-analysis to explore the impact of varying abstinence durations on semen quality and fertility outcomes.
METHODS
Three English database (PubMed, Embase, and Cochrane Central Register of Controlled Trials) as well as four Chinese database (China National Knowledge Infrastructure, Chinese Scientific Journals database, WanFang database, and Chinese Biomedical Literature database) were searched from 2000 to August 2023. The classical meta-analysis and "one-stage" dose-response meta-analysis were conducted to compare the associations of different abstinence durations (short-term abstinence vs. long-term abstinence) on semen quality in healthy adult and different type of infertile patients.
RESULTS
There were 85 eligible studies were finally included. The meta-analysis of volume (mean difference [MD] = -0.95 mL, 95% confidence interval [CI]: -1.16 to -0.74 mL), total sperm count (TSC) (MD = -102.45×10 , 95% CI: -117.98×10 to -86.91×10 ), sperm concentration (SC) (MD = -11.88×10 /mL, 95% CI: -18.96×10 /mL to -4.80×10 /mL), DNA fragmentation index (DFI) (MD = -2.37%, 95% CI: -4.73% to -0.01%) in healthy men showed a significant decrease with different abstinence durations (short-term abstinence vs. long-term abstinence). The meta-analysis of infertile men showed significant decrease in volume in various subgroups (MD range: -0.73 to -1.17 mL) with P < 0.01; TSC (MD = -61.93×10 , 95% CI: -88.84×10 to -35.01×10 ), SC (MD = -5.39×10 /mL, 95% CI: -9.97×10 to -0.81×10 /mL), DFI (MD = -5.63%, 95% CI: -10.19% to -1.06%) in unexplained infertility subgroup; significant increase in viability (MD = 6.14%, 95% CI: 3.61% to 8.68%) in the unexplained infertility subgroup. The dose-response meta-analysis showed that TSC in oligozoospermia showed a nonlinear increase (coefficient from 3.38 to -5.76, P from 0.02 to 0.22) and the truncation point was around the 4th to 5th abstinence day. The percentage of progressive motile sperm (PR) in asthenozoospermia showed a significant decrease (coefficient = -2.39, 95% CI: -4.28 to -0.50). For fertility outcomes of different ARTs, only the clinical pregnancy rate (CPR) in the intrauterine insemination (IUI) subgroup showed a significant decrease around the 3rd day (coefficient = 0.85, 95% CI: 0.75 to 0.97).
CONCLUSIONS
Short-term abstinence may be associated with limited improvements in semen quality in healthy men but could be more beneficial for infertile men, especially within the first 4 days of abstinence. Caution is urged in making definitive conclusions about the causal relationship between abstinence time and semen quality changes due to potential confounding and interactions.
PubMed: 38197853
DOI: 10.1111/andr.13583 -
Cells Mar 2023Epigenetic research has the potential to improve our understanding of the pathogenesis of cancer, specifically non-small-cell lung cancer, and support our efforts to... (Review)
Review
Epigenetic research has the potential to improve our understanding of the pathogenesis of cancer, specifically non-small-cell lung cancer, and support our efforts to personalize the management of the disease. Epigenetic alterations are expected to have relevance for early detection, diagnosis, outcome prediction, and tumor response to therapy. Additionally, epi-drugs as therapeutic modalities may lead to the recovery of genes delaying tumor growth, thus increasing survival rates, and may be effective against tumors without druggable mutations. Epigenetic changes involve DNA methylation, histone modifications, and the activity of non-coding RNAs, causing gene expression changes and their mutual interactions. This systematic review, based on 110 studies, gives a comprehensive overview of new perspectives on diagnostic (28 studies) and prognostic (25 studies) epigenetic biomarkers, as well as epigenetic treatment options (57 studies) for non-small-cell lung cancer. This paper outlines the crosstalk between epigenetic and genetic factors as well as elucidates clinical contexts including epigenetic treatments, such as dietary supplements and food additives, which serve as anti-carcinogenic compounds and regulators of cellular epigenetics and which are used to reduce toxicity. Furthermore, a future-oriented exploration of epigenetic studies in NSCLC is presented. The findings suggest that additional studies are necessary to comprehend the mechanisms of epigenetic changes and investigate biomarkers, response rates, and tailored combinations of treatments. In the future, epigenetics could have the potential to become an integral part of diagnostics, prognostics, and personalized treatment in NSCLC.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Epigenesis, Genetic; DNA Methylation
PubMed: 36980246
DOI: 10.3390/cells12060905 -
Biology of Sex Differences May 2018Differences in cardiovascular diseases are evident in men and women throughout life and are mainly attributed to the presence of sex hormones and chromosomes. Epigenetic...
BACKGROUND
Differences in cardiovascular diseases are evident in men and women throughout life and are mainly attributed to the presence of sex hormones and chromosomes. Epigenetic mechanisms drive the regulation of the biological processes that may lead to CVD and are possibly influenced by sex. In order to gain an overview of the status quo on sex differences in cardiovascular epigenetics, we performed a systematic review.
MATERIALS AND METHODS
A systematic search was performed on PubMed and Embase for studies mentioning cardiovascular disease, epigenetics, and anything related to sex differences. The search returned 3071 publications to be screened. Primary included publications focused on cardiovascular and epigenetics research. Subsequently, papers were assessed for including both sexes in their studies and checked for appropriate sex stratification of results.
RESULTS
Two independent screeners identified 75 papers in the proper domains that had included both sexes. Only 17% (13 papers out of 75) of these publications stratified some of their data according to sex. All remaining papers focused on DNA methylation solely as an epigenetic mechanism. Of the excluded papers that included only one sex, 86% (24 out 28) studied males, while 14% (4 out of 28) studied females.
CONCLUSION
Our overview indicates that the majority of studies into cardiovascular epigenetics do not show their data stratified by sex, despite the well-known sex differences in CVD. All included and sex-stratified papers focus on DNA methylation, indicating that a lot of ground is still to gain regarding other epigenetic mechanisms, like chromatin architecture, and histone modifications. More attention to sex in epigenetic studies is warranted as such integration will advance our understanding of cardiovascular disease mechanisms in men and women.
Topics: Cardiovascular Diseases; Epigenesis, Genetic; Female; Humans; Male; Sex Characteristics
PubMed: 29792221
DOI: 10.1186/s13293-018-0180-z -
Phytotherapy Research : PTR May 2018Fuzheng Huayu (FZHY) capsule, a formulated traditional Chinese medicine product with 6 Chinese herbs, is widely used for HBV-related cirrhosis as an adjuvant treatment.... (Meta-Analysis)
Meta-Analysis Review
Fuzheng Huayu (FZHY) capsule, a formulated traditional Chinese medicine product with 6 Chinese herbs, is widely used for HBV-related cirrhosis as an adjuvant treatment. However, the efficacy of FZHY capsule for HBV-induced cirrhosis did not be comprehensively proved by systematic analysis. Our current analysis was aimed to assess the efficacy and safety of FZHY capsule by an evidence-based method. Databases, including China National Knowledge Infrastructure, Wangfang, VIP medicine information system, Pubmed, Embase, and Cochrane Library, were searched, and the randomized controlled trials of FZHY capsule were used for the treatment of HBV-associated liver cirrhosis. Meta-analysis was performed by Review Manager 5.3. The efficacy rate, alanine transaminase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), albumin (ALB), Procollagen III protein (PIIIP), hyaluronic acid (HA), laminin (LN), Collagen C Type IV (IV-C), Child-Pugh score, portal vein diameter, spleen thickness, HBeAg negative conversion rate, and HBV-DNA negative conversion rate were systematically assessed. The Cochrane Risk of Bias tool was used to evaluate the methodological quality of eligible studies. Nineteen studies with 1,769 patients were included in the meta-analysis. Compared to conventional treatment, FZHY capsule was effective by increasing the efficacy. FZHY capsule was more efficient in improving ALT, AST, TBIL, PIIIP, HA, LN, IV-C, Child-Pugh grading score, portal vein diameter, spleen thickness, and HBV-DNA negative conversion rate with no serious adverse reactions. Nevertheless, a variety of well-designed randomized controlled trials are needed to confirm these findings since small samples were applied in the previous studies.
Topics: Capsules; China; Combined Modality Therapy; Drugs, Chinese Herbal; Hepatitis B; Hepatitis B virus; Humans; Liver Cirrhosis; Treatment Outcome
PubMed: 29235181
DOI: 10.1002/ptr.6009 -
Head and Neck Pathology Dec 2023The BRAF p.V600E genetic variant facilitates the pathogenesis of various tumors by triggering tumor proliferation and progression. The aim of this study was to analyze... (Review)
Review
BACKGROUND
The BRAF p.V600E genetic variant facilitates the pathogenesis of various tumors by triggering tumor proliferation and progression. The aim of this study was to analyze the prevalence of BRAF p.V600E in benign mixed epithelial and mesenchymal and malignant odontogenic tumors. In addition, we discussed the different detection methods used to assess for aberrant BRAF.
METHODS
This systematic review followed the PRISMA guidelines and was registered in Prospero (CRD42023445689). A comprehensive search of the PubMed/MEDLINE, Scopus, Web of Science, and Embase electronic databases was performed to answer the question "What is the prevalence of the BRAF p.V600E mutation in benign mixed and malignant odontogenic tumors?" The methodological quality of the selected studies was assessed using the JBI's Critical Appraisal Tool.
RESULTS
Initially, 387 records were identified, but only 11 articles met the inclusion criteria. A total of 70 patients with benign mixed epithelial and mesenchymal odontogenic tumors and 63 with malignant odontogenic tumors were included in the analysis. We found that the BRAF p.V600E mutation had a prevalence of 31.42% in mixed tumors and 26.98% in malignant odontogenic tumors. Moreover, immunohistochemistry showed high concordance with DNA-based molecular methods.
CONCLUSION
In general, the BRAF p.V600E variant exhibited a prominent prevalence in mixed and malignant odontogenic tumors. However, most of the findings are based on small cohorts of patients and further studies with larger cohorts are needed.
Topics: Humans; Mutation; Proto-Oncogene Proteins B-raf; Prevalence; Odontogenic Tumors; Mouth Neoplasms
PubMed: 38057461
DOI: 10.1007/s12105-023-01601-6 -
Cancer Treatment Reviews Dec 2017The potential predictive value of genetic polymorphisms in ovarian cancer first-line treatment is inconsistently reported. We aimed to review ovarian cancer... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The potential predictive value of genetic polymorphisms in ovarian cancer first-line treatment is inconsistently reported. We aimed to review ovarian cancer pharmacogenetic studies to update and summarize the available data and to provide directions for further research.
METHODS
A systematic review followed by a meta-analysis was conducted on cohort studies assessing the involvement of genetic polymorphisms in ovarian cancer first-line treatment response retrieved through a MEDLINE database search by November 2016. Studies were pooled and summary estimates and 95% confidence intervals (CI) were calculated using random or fixed-effects models as appropriate.
RESULTS
One hundred and forty-two studies gathering 106871 patients were included. Combined data suggested that GSTM1-null genotype patients have a lower risk of death compared to GSTM1-wt carriers, specifically in advanced stages (hazard ratio (HR), 0.68; 95% CI, 0.48-0.97) and when submitted to platinum-based chemotherapy (aHR, 0.61; 95% CI, 0.39-0.94). ERCC1 rs11615 and rs3212886 might have also a significant impact in treatment outcome (aHR, 0.67; 95% CI, 0.51-0.89; aHR, 1.28; 95% CI, 1.01-1.63, respectively). Moreover, ERCC2 rs13181 and rs1799793 showed a distinct ethnic behavior (Asians: aHR, 1.41; 95% CI, 0.80-2.49; aHR, 1.07; 95% CI, 0.62-1.86; Caucasians: aHR, 0.10; 95% CI, 0.01-0.96; aHR, 0.18; 95% CI, 0.05-0.68, respectively).
CONCLUSION(S)
The definition of integrative predictive models should encompass genetic information, especially regarding GSTM1 homozygous deletion. Justifying additional pharmacogenetic investigation are variants in ERCC1 and ERCC2, which highlight the DNA Repair ability to ovarian cancer prognosis. Further knowledge could aid to understand platinum-treatment failure and to tailor chemotherapy strategies.
Topics: Antineoplastic Combined Chemotherapy Protocols; Cytoreduction Surgical Procedures; Female; Genetic Variation; Glutathione Transferase; Humans; Models, Genetic; Organoplatinum Compounds; Ovarian Neoplasms; Polymorphism, Single Nucleotide; Taxoids; Treatment Outcome
PubMed: 29100168
DOI: 10.1016/j.ctrv.2017.10.001 -
Scientific Reports Oct 2022The association between the expression of Lysyl oxidase (LOX) and its clinicopathological parameters and prognosis in patients with gastric cancer (GC) is still... (Meta-Analysis)
Meta-Analysis
The association between the expression of Lysyl oxidase (LOX) and its clinicopathological parameters and prognosis in patients with gastric cancer (GC) is still disputed. We performed this meta-analysis and bioinformatics analysis to clarify the relationship between the expression and methylation level of LOX with its clinicopathological parameters and prognostic value. We applied odds ratios with a 95% confidence interval to study the associations between LOX expression and clinicopathological parameters and overall survival (OS) in GC patients. In addition, association analysis of promoter methylation levels and expression of LOX with its prognostic value was performed using the Cancer Genome Atlas (TCGA) and four Gene Expression Omnibus (GEO) datasets. The PRISMA 2020 checklist was used to guide the data extraction and analysis. This meta-analysis includes seven clinical studies with a total of 1435 GC patients. LOX expression was related to lymph node metastasis and tumor distant metastasis in GC patients, but not to gender, tumor differentiation, Lauren classification, or tumor depth of invasion. Patients with GC grouped in high-expression of LOX had a much worse OS than those in low-expression. In addition, TCGA and four GEO datasets with 1279 samples were included in the bioinformatics analysis. The bioinformatics analysis showed that patients with high LOX levels had poor OS; low levels of methylation at some cg sites in the LOX gene were strongly related to poor OS and PFS; and methylation levels of LOX are negatively correlated with advanced tumor stage. The conclusion from comprehensive DNA methylation and gene expression analysis supports LOX as a specific diagnostic and prognosis biomarker in GC. LOX expression was related to lymph node metastasis, tumor distant metastasis and poor prognosis in GC. Low methylation levels were related to advanced tumor stage and poor prognosis in GC. Integrative analysis supports LOX as a specific diagnostic and prognosis biomarker in GC.
Topics: Biomarkers; Biomarkers, Tumor; Computational Biology; Humans; Lymphatic Metastasis; Prognosis; Protein-Lysine 6-Oxidase; Stomach Neoplasms
PubMed: 36202905
DOI: 10.1038/s41598-022-21402-1