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NPJ Microgravity Jan 2024With increasing possibilities of multi-year missions in deep space, colonizing other planets, and space tourism, it is important to investigate the effects of space... (Review)
Review
With increasing possibilities of multi-year missions in deep space, colonizing other planets, and space tourism, it is important to investigate the effects of space travel on human reproduction. This study aimed to systematically review and summarize the results of available literature on space travel, microgravity, and space radiation, or Earth-based spaceflight analogues impact on female and male reproductive functions in humans. This systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and Space Biomedicine Systematic Review methods. The search was performed using three databases: PubMed, Web of Science, and Medline Complete. During the database search, 364 studies were identified. After the study selection process, 16 studies were included in the review. Five studies included female participants, and the findings show an increased risk of thromboembolism in combined oral contraceptive users, decreased decidualization, functional insufficiency of corpus luteum, and decreased progesterone and LH levels related to space travel or its simulation. Male participants were included in 13 studies. In males, reproductive health considerations focused on the decrease in testosterone and sex hormone-binding globulin levels, the ratio of male offspring, sperm motility, sperm vitality, and the increase in sperm DNA fragmentation related to space travel or its simulation. Results of this systematic review highlight the need to focus more on the astronaut's reproductive health in future research, as only 16 studies were found during the literature search, and many more research questions related to reproductive health in astronauts still need to be answered.
PubMed: 38238348
DOI: 10.1038/s41526-024-00351-1 -
Hematology/oncology and Stem Cell... Mar 2021Vitamin D is a steroid hormone that exerts its actions through ligation of the vitamin D receptor (VDR), a transcription factor of the nuclear receptor family. VDR has... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Vitamin D is a steroid hormone that exerts its actions through ligation of the vitamin D receptor (VDR), a transcription factor of the nuclear receptor family. VDR has not only physiologic actions in calcium metabolism but also several other cellular effects through extensive binding to the DNA and modification of genome expression. In cancer, it has neoplasia-suppressive effects and various mechanisms of action mediating cancer cell inhibition have been described. Vitamin D deficiency has been linked to increased risk of breast cancer. A role of the vitamin once the disease has been diagnosed is also probable.
METHODS
A systematic review and meta-analysis of studies that report on vitamin D levels (in the form of its main circulating metabolite, 25-hydroxyvitamin D [25-OHD]) in patients with newly diagnosed breast cancer was performed. Outcomes of interest included the levels of serum 25-OHD in patients with breast cancer, those of matched controlled, in studies that included controls, as well as respective percentages of patients and controls with deficient and insufficient 25-OHD levels.
RESULTS
A total of 25 studies (10 with controls and 15 without controls) provided data on the outcomes of interest. Populations from all continents, besides Australia, were represented in the studies. The mean level of 25-OHD in patients with breast cancer was 26.88 ng/mL (95% CI 22.8-30.96 ng/mL) and the mean level of 25-OHD in control patients was 31.41 ng/mL (95% CI 19.31-43.5 ng/mL). In the patients with breast cancer group, 45.28% (95% CI 24.37%-53.51%) had levels of 25-OHD below 20 ng/mL, whereas this percentage was 33.71% (95% CI 21.61%-45.82%) in controls. Similarly, 67.44% (95% CI 48.32%-86.55%) of patients with breast cancer had a baseline level of 25-OHD below 30 ng/mL, whereas this percentage was 33.71% (95% CI 21.61%-45.82%) in controls.
CONCLUSION
A high prevalence of vitamin D insufficiency is observed in patients with newly diagnosed breast cancer and may be linked pathophysiologically with breast cancer development or progression. Therapeutic benefits may be provided by manipulation of the vitamin D pathway in breast cancer.
Topics: Breast Neoplasms; Female; Humans; Vitamin D; Vitamin D Deficiency
PubMed: 33002425
DOI: 10.1016/j.hemonc.2020.08.005 -
PloS One 2024Meningioma is the most common primary brain tumor and many studies have evaluated numerous biomarkers for their prognostic value, often with inconsistent results.... (Meta-Analysis)
Meta-Analysis
Meningioma is the most common primary brain tumor and many studies have evaluated numerous biomarkers for their prognostic value, often with inconsistent results. Currently, no reliable biomarkers are available to predict the survival, recurrence, and progression of meningioma patients in clinical practice. This study aims to evaluate the prognostic value of immunohistochemistry-based (IHC) biomarkers of meningioma patients. A systematic literature search was conducted up to November 2023 on PubMed, CENTRAL, CINAHL Plus, and Scopus databases. Two authors independently reviewed the identified relevant studies, extracted data, and assessed the risk of bias of the studies included. Meta-analyses were performed with the hazard ratio (HR) and 95% confidence interval (CI) of overall survival (OS), recurrence-free survival (RFS), and progression-free survival (PFS). The risk of bias in the included studies was evaluated using the Quality in Prognosis Studies (QUIPS) tool. A total of 100 studies with 16,745 patients were included in this review. As the promising markers to predict OS of meningioma patients, Ki-67/MIB-1 (HR = 1.03, 95%CI 1.02 to 1.05) was identified to associate with poor prognosis of the patients. Overexpression of cyclin A (HR = 4.91, 95%CI 1.38 to 17.44), topoisomerase II α (TOP2A) (HR = 4.90, 95%CI 2.96 to 8.12), p53 (HR = 2.40, 95%CI 1.73 to 3.34), vascular endothelial growth factor (VEGF) (HR = 1.61, 95%CI 1.36 to 1.90), and Ki-67 (HR = 1.33, 95%CI 1.21 to 1.46), were identified also as unfavorable prognostic biomarkers for poor RFS of meningioma patients. Conversely, positive progesterone receptor (PR) and p21 staining were associated with longer RFS and are considered biomarkers of favorable prognosis of meningioma patients (HR = 0.60, 95% CI 0.41 to 0.88 and HR = 1.89, 95%CI 1.11 to 3.20). Additionally, high expression of Ki-67 was identified as a prognosis biomarker for poor PFS of meningioma patients (HR = 1.02, 95%CI 1.00 to 1.04). Although only in single studies, KPNA2, CDK6, Cox-2, MCM7 and PCNA are proposed as additional markers with high expression that are related with poor prognosis of meningioma patients. In conclusion, the results of the meta-analysis demonstrated that PR, cyclin A, TOP2A, p21, p53, VEGF and Ki-67 are either positively or negatively associated with survival of meningioma patients and might be useful biomarkers to assess the prognosis.
Topics: Meningioma; Humans; Biomarkers, Tumor; Prognosis; Meningeal Neoplasms; DNA Topoisomerases, Type II; Ki-67 Antigen; Tumor Suppressor Protein p53; Vascular Endothelial Growth Factor A; Immunohistochemistry; Poly-ADP-Ribose Binding Proteins
PubMed: 38758750
DOI: 10.1371/journal.pone.0303337 -
Journal of Biological Inorganic... Apr 2023Zinc finger proteins are abundant in the human proteome and are responsible for a variety of functions. The domains that constitute zinc finger proteins are compact... (Review)
Review
Zinc finger proteins are abundant in the human proteome and are responsible for a variety of functions. The domains that constitute zinc finger proteins are compact spherical structures, each comprising approximately 30 amino acid residues, but they also have precise molecular factor functions: zinc binding and DNA recognition. Due to the biological importance of zinc finger proteins and their unique structural and functional properties, many artificial zinc finger proteins have been created and are expected to improve their functions and biological applications. In this study, we review previous studies on the redesign and application of artificial zinc finger proteins, focusing on the experimental results obtained by our research group. In addition, we systematically review various design strategies used to construct artificial zinc finger proteins and discuss in detail their potential biological applications, including gene editing. This review will provide relevant information to researchers involved or interested in the field of artificial zinc finger proteins as a potential new treatment for various diseases.
Topics: Humans; Zinc Fingers; DNA
PubMed: 36749405
DOI: 10.1007/s00775-023-01991-6 -
Pathology, Research and Practice Jan 2022Medullary thyroid cancer (MTC) is the third frequent subtype of thyroid cancer-driving from thyroid C-cells. The first-line strategy to treat MTC is surgery, but tumor...
Medullary thyroid cancer (MTC) is the third frequent subtype of thyroid cancer-driving from thyroid C-cells. The first-line strategy to treat MTC is surgery, but tumor recurrence and patients' mortality rate have still been demonstrated in approximately 4-10% of MTC cases. Therefore, to treat and prevent the progressive form of the disease, the early diagnosis of MTC is assumed to play a critical role. In this regard, recently, circulating biomarkers have drawn researchers' attention for their nonaggressive manners in the sample collection. In this systematic review, we aimed to focus on circulating biomarkers and their applications in MTC diagnosis, prognosis and follow-up, and we discussed their clinical application and how they can affect clinical decision making in the future. A literature search (from 2000 to 2021) was accomplished on MTC circulating biomarkers in different databases, and only English articles were evaluated. We found that calcitonin (CT) and carcinoembryonic antigen (CEA) are the most important circulating biomarkers in the MTC diagnosis. Other circulating biomarkers included pro-calcitonin (Pro-CT), pro-Gastrin releasing peptide (Pro-GRP), carbohydrate antigen 19-9 (CA 19-9) and chromogranin A (CgA). Some novel circulating biomarkers comprised vaspin and retinol-binding protein-4 (RBP4), myostatin, tumor cells (CTCs), RET M918T mutated cfDNA, circulating tumor DNA (ctDNA), miR-375 and Alu83 and Alu244 cfDNAs. Several circulating biomarkers have been identified to optimize the accuracy of diagnosis and offer new prognostic criteria, which should be verified before any clinical application. Although different circulating biomarkers contributed to MTC have been discovered, a few of them could be used in clinical diagnosis. In many cases, the application of each marker may not be useful lonely; therefore, a combination of two or more biomarkers could open a new avenue in the diagnosis, prognosis and prediction of MTC.
Topics: Biomarkers, Tumor; Carcinoma, Neuroendocrine; Humans; Prognosis; Thyroid Neoplasms
PubMed: 34929598
DOI: 10.1016/j.prp.2021.153694 -
Circulation. Genomic and Precision... Aug 20231p36 deletion syndrome can predispose to pediatric-onset cardiomyopathy. Deletion breakpoints are variable and may delete the transcription factor . Early studies...
BACKGROUND
1p36 deletion syndrome can predispose to pediatric-onset cardiomyopathy. Deletion breakpoints are variable and may delete the transcription factor . Early studies suggest that deletion of may underlie cardiomyopathy in patients with 1p36 deletion; however, the prognostic impact of loss is unknown.
METHODS
This retrospective cohort included subjects with 1p36 deletion syndrome from 4 hospitals. Prevalence of cardiomyopathy and freedom from death, cardiac transplantation, or ventricular assist device were analyzed. A systematic review cohort was derived for further analysis. A cardiac-specific knockout mouse ( conditional knockout) was generated. Echocardiography was performed at 4 and 6 to 7 months. Histology staining and qPCR were performed at 7 months to assess fibrosis.
RESULTS
The retrospective cohort included 71 patients. Among individuals with deleted, 34.5% developed cardiomyopathy versus 7.7% of individuals with not deleted (=0.1). In the combined retrospective and systematic review cohort (n=134), deletion-associated cardiomyopathy risk was recapitulated and significant (29.1% versus 10.8%, =0.03). deletion was associated with increased risk of death, cardiac transplant, or ventricular assist device (=0.04). Among those deleted, 34.5% of females developed cardiomyopathy versus 16.7% of their male counterparts (=0.2). We find sex-specific differences in the incidence and the severity of contractile dysfunction and fibrosis in female conditional knockout mice. Further, female conditional knockout mice demonstrate significantly elevated risk of mortality (=0.0003).
CONCLUSIONS
deletion is associated with a significantly increased risk of cardiomyopathy and cardiac mortality. conditional knockout mice develop cardiomyopathy in a sex-biased way. Patients with deletion should be assessed for cardiac disease.
Topics: Animals; Female; Humans; Male; Mice; Cardiomyopathies; DNA-Binding Proteins; Fibrosis; Mice, Knockout; Multicenter Studies as Topic; Retrospective Studies; Transcription Factors
PubMed: 37395136
DOI: 10.1161/CIRCGEN.122.003912 -
Clinical Oncology (Royal College of... Jul 2024ERCC1 rs11615 and ERCC2 rs238406 single nuclear polymorphism (SNPs) are known for their association with treatment outcome, likely related to radiosensitivity of both... (Meta-Analysis)
Meta-Analysis
AIMS
ERCC1 rs11615 and ERCC2 rs238406 single nuclear polymorphism (SNPs) are known for their association with treatment outcome, likely related to radiosensitivity of both tumor and normal tissue in patients with non-small-cell lung cancer. This study aimed to review the effect of 1) these ERCC1/2 SNPs and 2) other SNPs of DNA repair genes on radiation pneumonitis (RP) in patients with lung cancer.
MATERIALS AND METHODS
SNPs of our interest included ERCC1 rs11615 and ERCC2 rs238406 and other genes of DNA repair pathways that are functional and biologically active. DNA repair SNPs reported by at least two independent studies were pooled for meta-analysis. The study endpoint was radiation pneumonitis (RP) after radiotherapy. Recessive, dominant, homozygous, heterozygous, and allelic genotype models were used where appropriate.
RESULTS
A total of 16 studies (3080 patients) were identified from the systematic review and 12 studies (2090 patients) on 11 SNPs were included in the meta-analysis. The SNPs were ATM rs189037, ATM rs373759, NEIL1 rs4462560, NEIL1 rs7402844, APE1 rs1130409, XRCC3 rs861539, ERCC1 rs11615, ERCC1 rs3212986, ERCC2 rs238406, ERCC2 rs13181, and XRCC1 rs25487. ERCC1 rs11615 (236 patients) and ERCC2 rs238406 (254 patients) were not significantly associated with RP. Using the allelic model, the G allele for NEIL1 gene was significantly associated with a reduced odds of developing symptomatic (grade ≥2) RP compared to the C allele for rs7402844 (OR 0.70, 95% CI: 0.49, 0.99, P = 0.04). Similarly, the T allele for APE1 gene was significantly associated with a reduced odds of developing symptomatic (grade ≥2) RP compared to the G allele for rs1130409 (OR 0.59, 95% CI: 0.43, 0.81, P = 0.001).
CONCLUSION
Genetic variation in the DNA repair pathway genes may play a significant role in the risk of developing radiation pneumonitis in patients with lung cancer. Further studies are needed on genotypic features of DNA repair pathway genes and their association with treatment sensitivity, as such knowledge may guide personalized radiation dose prescription.
Topics: Humans; Radiation Pneumonitis; Lung Neoplasms; DNA Repair; Polymorphism, Single Nucleotide; Xeroderma Pigmentosum Group D Protein; DNA-Binding Proteins; Endonucleases; Genetic Predisposition to Disease; Carcinoma, Non-Small-Cell Lung
PubMed: 38653664
DOI: 10.1016/j.clon.2024.03.019 -
European Journal of Clinical... May 2022Many drugs are associated with the risk of QT prolongation and torsades de pointes (TdP), and different risk assessment tools (RATs) are developed to help clinicians to... (Review)
Review
PURPOSE
Many drugs are associated with the risk of QT prolongation and torsades de pointes (TdP), and different risk assessment tools (RATs) are developed to help clinicians to manage related risk. The aim of this systematic review was to summarize the evidence of different RATs for QT prolonging pharmacotherapy.
METHODS
A systematic review was conducted using PubMed and Scopus databases. Studies concerning risk assessment tools for QT prolonging pharmacotherapy, including older adults, were included. Screening and selection of the studies, data extraction, and risk of bias assessment were undertaken.
RESULTS
A total of 21 studies were included, involving different risk assessment tools. Most commonly used tools were risk scores (n = 9), computerized physician order entry systems (n = 3), and clinical decision support systems (n = 6). The tools were developed mainly for physicians and pharmacists. Risk scores included a high number of risk factors, both pharmacological and non-pharmacological, for QT prolongation and TdP. The inclusion of patients' risk factors in computerized physician order entry and clinical decision support systems varied.
CONCLUSION
Most of the risk assessment tools for QT prolonging pharmacotherapy give a comprehensive overview of patient-specific risks of QT prolongation and TdP and reduce modifiable risk factors and actual events. The risk assessment tools could be better adapted to different health information systems to help in clinical decision-making. Further studies on clinical validation of risk assessment tools with randomized controlled trials are needed.
Topics: Aged; DNA-Binding Proteins; Electrocardiography; Humans; Long QT Syndrome; Risk Assessment; Risk Factors; Torsades de Pointes
PubMed: 35156131
DOI: 10.1007/s00228-022-03285-3 -
Neuropathology and Applied Neurobiology Dec 2022Over the past decade, considerable efforts have been made to accelerate pathophysiological understanding of fatal neurodegenerative diseases such as amyotrophic lateral... (Review)
Review
Over the past decade, considerable efforts have been made to accelerate pathophysiological understanding of fatal neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) with brain banks at the forefront. In addition to exploratory disease mechanisms, brain banks have aided our understanding with regard to clinical diagnosis, genetics and cell biology. Across neurodegenerative disorders, the impact of brain tissue in ALS research has yet to be quantified. This review aims to outline (i) how postmortem tissues from brain banks have influenced our understanding of ALS over the last 15 years, (ii) correlate the location of dedicated brain banks with the geographical prevalence of ALS, (iii) identify the frequency of features reported from postmortem studies and (iv) propose common reporting standards for materials obtained from dedicated brain banks. A systematic review was conducted using PubMed and Web of Science databases using key words. From a total of 1439 articles, 73 articles were included in the final review, following PRISMA guidelines. Following a thematic analysis, articles were categorised into five themes; clinico-pathological (13), genetic (20), transactive response DNA binding protein 43 (TDP-43) pathology (12), non-TDP-43 neuronal pathology (nine) and extraneuronal pathology (19). Research primarily focused on the genetics of ALS, followed by protein pathology. About 63% of the brain banks were in the United States of America and United Kingdom. The location of brain banks overall aligned with the incidence of ALS worldwide with 88% of brain banks situated in Europe and North America. An overwhelming lack of consistency in reporting and replicability was observed, strengthening the need for a standardised reporting system. Overall, postmortem material from brain banks generated substantial new knowledge in areas of genetics and proteomics and supports their ongoing role as an important research tool.
Topics: Humans; Amyotrophic Lateral Sclerosis; Knowledge Discovery; Brain; Neurons; United Kingdom
PubMed: 35921237
DOI: 10.1111/nan.12845 -
European Journal of Cancer Prevention :... Nov 2020High mobility group A protein-2 (HMGA2) is an architectural transcription factor that binds to the A/T-rich DNA minor groove and is responsible for regulating... (Meta-Analysis)
Meta-Analysis
High mobility group A protein-2 (HMGA2) is an architectural transcription factor that binds to the A/T-rich DNA minor groove and is responsible for regulating transcriptional activity of multiple genes indirectly through chromatin change and assembling enhanceosome. HMGA2 is overexpressed in multiple tumor types, suggesting its involvement in cancer initiation and progression, thus, making it an ideal candidate for cancer diagnostic and prognostic. We performed a systematic review to examine the role of HMGA2 as a universal tumor cancer diagnostic and prognostic marker. We used Reporting Recommendations for Tumor Marker Prognostic Studies to systematically search OvidMedline, PubMed, and the Cochrane Library for English language studies, published between 1995 and June 2019. Meta-analysis provided pooled risk estimates and their 95% confidence intervals (CIs) for an association between overall survival and recurrence of cancers for studies with available estimates. We identified 42 eligible studies with a total of 5123 tumor samples in 15 types of cancer. The pooled percentage of HMGA2 gene expression in tumor samples was 65.14%. Meta-analysis showed that cancer patients with HMGA2 positive have significantly reduced survival, compared to patients without HMGA2 gene [pooled-hazard ratio (HR) = 1.85, 95% CI 1.48-2.22]. There was a positive association between cancer patients with HMGA2 overexpression and cancer recurrence though this association did not reach significance (pooled-HR = 1.44, 95% CI 0.80-2.07). Overexpression of HMGA2 was found in 15 types of cancer. There was an association between HMGA2 overexpression with reduced survival of cancer patients. HMGA2 is thus considered a promising universal tumor marker for prognostics.
Topics: Biomarkers, Tumor; Combined Modality Therapy; HMGA2 Protein; Humans; Neoplasms; Prognosis; Survival Rate
PubMed: 32898013
DOI: 10.1097/CEJ.0000000000000602