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Genetic Testing and Molecular Biomarkers May 2020Lung cancer is the leading cause of cancer-related deaths worldwide, imposing an enormous economic burden on society. Several studies have identified a link between the... (Meta-Analysis)
Meta-Analysis
Lung cancer is the leading cause of cancer-related deaths worldwide, imposing an enormous economic burden on society. Several studies have identified a link between the genetic polymorphisms in vitamin D pathways and lung cancer risk; however, the results remain inconclusive. The aim of this study was to estimate the effect of polymorphisms in the vitamin D receptor () and genes on lung cancer risk. Eligible case-control studies published between January 2000 and December 2018 were searched and studied. The pooled odds ratio and its 95% confidence interval were used to estimate the effect. Fifteen articles that included 4732 lung cancer patients and 4337 controls were identified for this study. Our results demonstrated that the polymorphism ( < 0.05) and the TC and TT+TC genotypes of the polymorphism ( < 0.05) were protective factors for avoiding lung cancer incidence, while the T allele and the TT genotype of polymorphism ( < 0.05) were risk factors for lung cancer. Ethnicity-based subgroup analyses indicated that the AA genotype of both the and the polymorphisms decreased lung cancer risk in Asians, while and polymorphisms increased lung cancer risk in Asians. Subgroup analysis by cancer subtypes showed that certain alleles and genotypic structures of the , , , and rs7041 were associated with nonsmall-cell lung cancer risk. Subgroup analysis by smoking status showed that the interaction between the TT genotype of and smoking increased the risk of lung cancer. Subgroup analysis with regard to gender showed that the AA+Aa genotype of decreased lung cancer risk in male patients. Our results suggest that the and polymorphisms decreased lung cancer risk, while the polymorphism increased lung cancer risk. Moreover, the AA genotype of the and variants were protective factors in Asian populations, whereas the and polymorphisms were risk factors for lung cancer in Asian populations. Future case-control studies with different ethnicities are still needed to generalize these associations.
Topics: Case-Control Studies; DNA-Binding Proteins; Female; Genetic Predisposition to Disease; Genotype; Humans; Incidence; Lung Neoplasms; Male; Odds Ratio; Polymorphism, Genetic; Receptors, Calcitriol; Risk Factors; Transcription Factors; Vitamin D
PubMed: 32255717
DOI: 10.1089/gtmb.2019.0187 -
Journal of Clinical Medicine Aug 2022: In the last 40 years, assisted reproductive techniques (ARTs) have emerged as potentially resolving procedures for couple infertility. This study aims to evaluate... (Review)
Review
: In the last 40 years, assisted reproductive techniques (ARTs) have emerged as potentially resolving procedures for couple infertility. This study aims to evaluate whether ART is associated with epigenetic dysregulation in the offspring. . To accomplish this, we collected all available data on methylation patterns in offspring conceived after ART and in spontaneously conceived (SC) offspring. We extracted 949 records. Of these, 50 were considered eligible; 12 were included in the quantitative synthesis. Methylation levels of CCCTC-binding factor 3 (CTCF3) were significantly lower in the ART group compared to controls (SMD -0.81 (-1.53; -0.09), I = 89%, = 0.03). In contrast, CCCTC-binding factor 6 (CTCF6), (), (), and () were not differently methylated in ART vs. SC offspring. : The methylation pattern of the offspring conceived after ART may be different compared to spontaneous conception. Due to the lack of studies and the heterogeneity of the data, further prospective and well-sized population studies are needed to evaluate the impact of ART on the epigenome of the offspring.
PubMed: 36078985
DOI: 10.3390/jcm11175056 -
Medicine Mar 2021Chromodomain helicase DNA-binding protein 1-like (CHD1L) is an oncogene. It was cloned from 1q21 chromosome region of hepatocellular carcinoma in 1991. CHD1L is... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Chromodomain helicase DNA-binding protein 1-like (CHD1L) is an oncogene. It was cloned from 1q21 chromosome region of hepatocellular carcinoma in 1991. CHD1L is up-regulated in many kinds of cancers and is involved in the carcinogenesis and development of tumors. More and more studies have shown that over-expression of CHD1L is associated with poor prognosis of tumors. The purpose of this study was to evaluate the prognostic value of CHD1L in human solid tumors.
METHODS
The key words in the database of PubMed, Web of Science, Embase, Cochrane library, and TCGA were searched for systematic literature retrieval. We collected relevant articles and data about CHD1L and prognosis of cancer and screened them according to the eligible criteria to evaluate the prognostic value of CHD1L in cancer patients. Then Stata SE12.0 software is used to analyze the data.
RESULTS
In our meta-analysis, 2720 patients with a total of 15 articles involving multiple types of tumors showed that high expression levels of CHD1L were associated with shorter overall survival (OS) (hazard ratio = 2.21, 95% confidence interval [CI]: (1.49-3.30)] and (hazard ratio = 1.16, 95% CI: (1.01-1.32)] in the TCGA database, in addition, the pooled odds ratios (ORs) indicated high expression levels of CHD1L in tumors significantly are associated with TNM stage (OR = 1.61, 95% CI: 1.01-2.55, P < .05), tumor size (OR = 1.38, 95% CI: 1.07-1.78, P < .05), tumor differentiation (OR = 2.13, 95% CI: 1.43-3.16, P < .05), and distant metastasis (OR = 1.86, 95% CI: 1.45-2.39 P < .05). However, we did not observe a significant correlation between the high expression of CHD1L and age, gender.
CONCLUSION
The high expression of CHD1L is associated with poor OS as well as related to tumor differentiation, tumor size, and distant metastasis, which can be served as a prognostic marker and a potential predictor of clinical pathology in human solid tumors.
Topics: Biomarkers, Tumor; DNA Helicases; DNA-Binding Proteins; Humans; Neoplasm Metastasis; Neoplasms; Prognosis; Survival Analysis; Tumor Burden; Up-Regulation
PubMed: 33725840
DOI: 10.1097/MD.0000000000024851 -
Calcified Tissue International Apr 2023Alopecia in hereditary vitamin D resistant rickets (HVDRR) has some correlation with severe rickets and poor overall response. However, these observations are based on...
Alopecia in hereditary vitamin D resistant rickets (HVDRR) has some correlation with severe rickets and poor overall response. However, these observations are based on small series. Hence, we aim to assess the genotypic spectrum of HVDRR and its correlation with alopecia and clinical response. Seven genetically-proven HVDDR patients from five unrelated families and 119 probands from systematic review were analysed retrospectively for phenotypic and genotypic data and overall response to therapy. In our cohort mean age at rickets onset was 12 (± 3.4) months. Alopecia was present in all patients but one. All patients had poor overall response to oral high-dose calcium and calcitriol and most required intravenous calcium. Genetic analyses revealed four novel variants. On systematic review, alopecia was present in majority (81.5%) and preceded the onset of rickets. Patients with alopecia had higher serum calcium (7.6 vs.6.9 mg/dl, p = 0.008), lower 1, 25(OH) D (200 vs.320 pg/ml, p = 0.03) and similar overall response to oral therapy (28.7% vs. 35.3%, p = 0.56). Alopecia was present in 51.4% of non-truncating (NT) ligand-binding domain (LBD) variants, whereas it was universal in truncating LBD and all DNA binding-domain (DBD) variants. Overall response to oral therapy was highest in LBD-NT (46.4%) as compared to 7.6% in LBD-truncating and 19% in DBD-NT variants. Among LBD-NT variants, those affecting RXR heterodimerization, but not those affecting ligand affinity, were associated with alopecia. Both alopecia and overall response have genotypic correlation. Age at diagnosis and overall response to oral therapy were similar between patients with and without alopecia in genetically proven HVDRR.
Topics: Humans; Infant; Familial Hypophosphatemic Rickets; Receptors, Calcitriol; Calcium; Ligands; Retrospective Studies; Alopecia; Mutation; Vitamin D
PubMed: 36705686
DOI: 10.1007/s00223-023-01061-8 -
Acta Neuropathologica Communications Aug 2022Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with repetitive head trauma and is characterised by the perivascular accumulation of... (Review)
Review
Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with repetitive head trauma and is characterised by the perivascular accumulation of hyperphosphorylated tau (p-tau) in the depths of cortical sulci. CTE can only be diagnosed postmortem and the cellular mechanisms of disease causation remain to be elucidated. Understanding the full scope of the pathological changes currently identified in CTE is necessary to identify areas requiring further research. This systematic review summarises the current literature on CTE pathology from postmortem human tissue histology studies published until 31 December 2021. Publications were included if they quantitively or qualitatively compared postmortem human tissue pathology in CTE to neuropathologically normal cases or other neurodegenerative diseases such as Alzheimer's disease (AD). Pathological entities investigated included p-tau, beta-amyloid, TDP-43, Lewy bodies, astrogliosis, microgliosis, axonopathy, vascular dysfunction, and cell stress. Of these pathologies, p-tau was the most frequently investigated, with limited reports on other pathological features such as vascular dysfunction, astrogliosis, and microgliosis. Consistent increases in p-tau, TDP-43, microgliosis, axonopathy, and cell stress were reported in CTE cases compared to neuropathologically normal cases. However, there was no clear consensus on how these pathologies compared to AD. The CTE cases used for these studies were predominantly from the VA-BU-CLF brain bank, with American football and boxing as the most frequent sources of repetitive head injury exposure. Overall, this systematic review highlights gaps in the literature and proposes three priorities for future research including: 1. The need for studies of CTE cases with more diverse head injury exposure profiles to understand the consistency of pathology changes between different populations. 2. The need for more studies that compare CTE with normal ageing and AD to further clarify the pathological signature of CTE for diagnostic purposes and to understand the disease process. 3. Further research on non-aggregate pathologies in CTE, such as vascular dysfunction and neuroinflammation. These are some of the least investigated features of CTE pathology despite being implicated in the acute phase response following traumatic head injury.
Topics: Alzheimer Disease; Chronic Traumatic Encephalopathy; DNA-Binding Proteins; Gliosis; Humans; Neurodegenerative Diseases; Neuropathology; tau Proteins
PubMed: 35933388
DOI: 10.1186/s40478-022-01413-9 -
Cancers Oct 2021In CRC, screening compliance is decreased due to the experienced discomfort associated with colonoscopy, although this method is the gold standard in terms of... (Review)
Review
In CRC, screening compliance is decreased due to the experienced discomfort associated with colonoscopy, although this method is the gold standard in terms of sensitivity and specificity. Promoter DNA methylation (hypomethylation or hypermethylation) has been linked to all CRC stages. Study objectives: to systematically review the current knowledge on approved biomarkers, reveal new potential ones, and inspect tactics that can improve performance. This research was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines; the risk of bias was evaluated using the revised Quality Assessment of Diagnostic Accuracy Studies criteria (QUADAS-2). The Web of Science Core Collection, MEDLINE and Scopus databases were searched for original articles published in peer-reviewed journals with the specific keywords "colorectal cancer", "early detection", "early-stage colorectal cancer", "epigenetics", "biomarkers", "DNA methylation biomarkers", "stool or blood or tissue or biopsy", "NDRG4", "BMP3", "SEPT9", and "SDC2". Based on eligibility criteria, 74 articles were accepted for analysis. mSDC2 and mSEPT9 were frequently assessed in studies, alone or together as part of the ColoDefense panel test-the latter with the greatest performance. mBMP3 may not be an appropriate marker for detecting CRC. A panel of five methylated binding sites of the CTCF gene holds the promise for early-stage specific detection of CRC. CRC screening compliance and accuracy can be enhanced by employing a stool mt-DNA methylation test.
PubMed: 34638449
DOI: 10.3390/cancers13194965 -
Biomedicines Jan 2024Acute myeloid leukemia (AML) is a diverse group of leukemias characterized by the uncontrolled proliferation of clonal neoplastic hematopoietic precursor cells with... (Review)
Review
Acute myeloid leukemia (AML) is a diverse group of leukemias characterized by the uncontrolled proliferation of clonal neoplastic hematopoietic precursor cells with chromosomal rearrangements and multiple gene mutations and the impairment of normal hematopoiesis. Current efforts to improve AML outcomes have focused on developing targeted therapies that may allow for improved antileukemic effects while reducing toxicity significantly. Gemtuzumab ozogamicin (GO) is one of the most thoroughly studied molecularly targeted therapies in adults. GO is a monoclonal antibody against CD33 IgG4 linked to the cytotoxic drug calicheamicin DMH. The use of GO as a chemotherapeutic agent is not generalized for all patients who suffer from AML, particularly for those whose health prevents them from using intensive conventional chemotherapy, in which case it can be used on its own, and those who have suffered a first relapse, where its combination with other chemotherapeutic agents is possible. This systematic review aimed to comprehensively evaluate GO, focusing on its molecular structure, mode of action, pharmacokinetics, recommended dosage, resistance mechanisms, and associated toxicities to provide valuable information on the potential benefits and risks associated with its clinical use. A systematic review of eight scientific articles from 2018 to 2023 was conducted using PRISMA analysis. The results showed that GO treatment activates proapoptotic pathways and induces double-strand breaks, initiating DNA repair mechanisms. Cells defective in DNA repair pathways are susceptible to GO cytotoxicity. GO has recommended doses for newly diagnosed CD33+ AML in combination or as a single agent. Depending on the treatment regimen and patient status, GO doses vary for induction, consolidation, and continuation cycles. Multidrug resistance (MDR) involving P-glycoprotein (P-gp) is associated with GO resistance. The overexpression of P-gp reduces GO cytotoxicity; inhibitors of P-gp can restore sensitivity. Mitochondrial pathway activation and survival signaling pathways are linked to GO resistance. Other resistance mechanisms include altered pharmacokinetics, reduced binding ability, and anti-apoptotic mechanisms. GO has limited extramedullary toxicity compared to other AML treatments and may cause hepatic veno-occlusive disease (HVOD). The incidence of hepatic HVOD after GO therapy is higher in patients with high tumor burden. Hematological side effects and hepatotoxicity are prominent, with thrombocytopenia and neutropenia observed. In conclusion, GO's reintroduction in 2017 followed a thorough FDA review considering its altered dose, dosing schedule, and target population. The drug's mechanism involves CD33 targeting and calicheamicin-induced DNA damage, leading to apoptosis and resistance mechanisms, including MDR and survival signaling, which impact treatment outcomes. Despite limited extramedullary toxicity, GO is associated with hematological side effects and hepatotoxicity.
PubMed: 38255313
DOI: 10.3390/biomedicines12010208 -
Diagnostic Pathology Mar 2024Amyotrophic lateral sclerosis (ALS) is a progressive and fatal motor neuron disease. Due to the limited knowledge about potential biomarkers that help in early diagnosis... (Review)
Review
BACKGROUND
Amyotrophic lateral sclerosis (ALS) is a progressive and fatal motor neuron disease. Due to the limited knowledge about potential biomarkers that help in early diagnosis and monitoring disease progression, today's diagnoses are based on ruling out other diseases, neurography, and electromyography examination, which takes a time-consuming procedure.
METHODS
PubMed, ScienceDirect, and Web of Science were explored to extract articles published from January 2015 to June 2023. In the searching strategy following keywords were included; amyotrophic lateral sclerosis, biomarkers, cerebrospinal fluid, serum, and plama.
RESULTS
A total number of 6 studies describing fluid-based exosomal biomarkers were included in this study. Aggregated proteins including SOD1, TDP-43, pTDP-43, and FUS could be detected in the microvesicles (MVs). Moreover, TDP-43 and NFL extracted from plasma exosomes could be used as prognostic biomarkers. Also, downregulated miR-27a-3p detected through exoEasy Maxi and exoQuick Kit in the plasma could be measured as a diagnostic biomarker. Eventually, the upregulated level of CORO1A could be used to monitor disease progression.
CONCLUSION
Based on the results, each biomarker alone is insufficient to evaluate ALS. CNS-derived exosomes contain multiple ALS-related biomarkers (SOD1, TDP-43, pTDP-43, FUS, and miRNAs) that are detectable in cerebrospinal fluid and blood is a proper alternation. Exosome detecting kits listed as exoEasy, ExoQuick, Exo-spin, ME kit, ExoQuick Plus, and Exo-Flow, are helpful to reach this purpose.
Topics: Humans; Exosomes; Amyotrophic Lateral Sclerosis; Superoxide Dismutase-1; Biomarkers; DNA-Binding Proteins; Disease Progression
PubMed: 38429818
DOI: 10.1186/s13000-024-01473-6 -
International Journal of Clinical... 2022The purpose of this study was to clarify the role of genetic factors on posttransplant diabetes mellitus (PTDM) risk. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
The purpose of this study was to clarify the role of genetic factors on posttransplant diabetes mellitus (PTDM) risk.
METHODS
Relevant publications were systematically retrieved from PubMed, EMBASE, and the Cochrane Library up to December 2020. Data from eligible case-control and cohort studies were extracted for qualitative and quantitative analyses. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to estimate the association between gene polymorphisms and PTDM in the quantitative meta-analysis.
RESULTS
A total of 43 eligible articles were identified, and 16 studies on 9 DNA variants from 8 genes were included in the meta-analysis. rs7903146 was significantly associated with PTDM risk in 5 genetic models (OR (95% CI): allelic: 1.59 (1.17-2.16), =0.003; dominant recessive: 1.62 (1.14, 2.31), =0.007; recessive: 1.87 (1.18, 2.94), =0.007; homozygote: 2.21 (1.23, 3.94), =0.008; and heterozygote 1.50 (1.08, 2.10), =0.017). rs2237892 was significantly correlated with PTDM risk in 3 genetic models (allelic: 0.68 (0.58, 0.81), < 0.001; dominant: 0.6 (049, 0.74), < 0.001; and heterozygote: 0.61 (0.48, 0.76), < 0.001). rs5219 was significantly linked with PTDM in the recessive genetic model (1.59 (1.01, 2.50), =0.047). No significant correlations of PTDM with rs12255372, rs13266634, rs1801282, rs10811661, rs1111875, and rs4402960 polymorphisms were found.
CONCLUSIONS
The gene polymorphisms of rs7903146, rs2237892, and rs5219 may predispose kidney transplant recipients to PTDM. Large sample size studies on diverse ethnic populations were warranted to confirm our findings.
Topics: Diabetes Mellitus, Type 2; Genetic Predisposition to Disease; Humans; KCNQ1 Potassium Channel; Kidney; Polymorphism, Single Nucleotide; RNA-Binding Proteins
PubMed: 35685576
DOI: 10.1155/2022/7140024 -
Signal Transduction and Targeted Therapy Oct 2020Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging virus that is highly pathogenic and has caused the recent worldwide pandemic officially named...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging virus that is highly pathogenic and has caused the recent worldwide pandemic officially named coronavirus disease (COVID-19). Currently, considerable efforts have been put into developing effective and safe drugs and vaccines against SARS-CoV-2. Vaccines, such as inactivated vaccines, nucleic acid-based vaccines, and vector vaccines, have already entered clinical trials. In this review, we provide an overview of the experimental and clinical data obtained from recent SARS-CoV-2 vaccines trials, and highlight certain potential safety issues that require consideration when developing vaccines. Furthermore, we summarize several strategies utilized in the development of vaccines against other infectious viruses, such as severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), with the aim of aiding in the design of effective therapeutic approaches against SARS-CoV-2.
Topics: Angiotensin-Converting Enzyme 2; Antibodies, Viral; Betacoronavirus; COVID-19; COVID-19 Vaccines; Clinical Trials as Topic; Coronavirus Infections; Gene Expression Regulation; Humans; Immunity, Innate; Immunization Schedule; Immunogenicity, Vaccine; Middle East Respiratory Syndrome Coronavirus; Pandemics; Patient Safety; Peptidyl-Dipeptidase A; Pneumonia, Viral; Protein Binding; Receptors, Virus; Severe acute respiratory syndrome-related coronavirus; SARS-CoV-2; Severe Acute Respiratory Syndrome; Spike Glycoprotein, Coronavirus; Vaccines, Attenuated; Vaccines, DNA; Vaccines, Subunit; Vaccines, Virus-Like Particle; Viral Vaccines
PubMed: 33051445
DOI: 10.1038/s41392-020-00352-y