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Molecular Genetics & Genomic Medicine Nov 2023Among present reports, the T/G allelic variation at the rs2609255 locus of the family sequence similarity gene 13A (FAM13A) was considerable associated with... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Among present reports, the T/G allelic variation at the rs2609255 locus of the family sequence similarity gene 13A (FAM13A) was considerable associated with susceptibility to interstitial lung diseases (ILDs). In this study, we summarized relevant studies and applied a meta-analysis to explore whether the polymorphism of rs2609255 site of the FAM13A gene can be utilized to predict susceptibility to idiopathic pulmonary fibrosis (IPF) patients or rheumatoid arthritis-associated interstitial lung disease (RA-ILD) or silicosis patients in different populations for the first time.
METHODS
We compared the frequency of G allele on rs2609255 site of FAM13A between the control subjects and IPF or RA-ILD or silicosis patients from different races by using meta-analysis. Nine studies were involved in this meta-analysis, including five IPF studies, two RA-ILD studies, and two silicosis studies, and containing 14 subgroups. We conducted separate meta-analyses for different races.
RESULTS
In all individuals, a substantial link between the G allele of the FAM13A rs2609255 polymorphism and IPF (OR: 1.47, 95% CI: 1.33-1.63, p < 0.00001) was indicated. After dividing by ethnicity, the G allele was illustrated to be considerable correlation with IPF in Asian (OR: 2.63, 95% CI: 1.81-3.81, p < 0.00001) and with RA-ILD individuals (OR: 3.27, 95% CI: 1.26-8.49, p = 0.01). Conversely, there was no correlation with the G allele and IPF in European individuals (OR: 1.27, 95% CI: 0.89-1.83, p = 0.13) or silicosis in Chinese individuals (OR: 1.20, 95% CI: 0.99-1.46, p = 0.07).
CONCLUSION
This is the first meta-analysis that provides evidence that the rs2609255 of FAM13A might increase susceptibility to RA-ILD, and IPF especially in Asian but not in European individuals, and not be correlated with silicosis in Chinese individuals, which indicated the differences in susceptibility to disease by race were noteworthy.
Topics: Humans; Lung Diseases, Interstitial; Idiopathic Pulmonary Fibrosis; Polymorphism, Genetic; Arthritis, Rheumatoid; Silicosis; GTPase-Activating Proteins
PubMed: 37786320
DOI: 10.1002/mgg3.2279 -
Genes Jan 2023The ethylene-responsive element binding factor-associated amphiphilic repression (EAR) motif, defined by the consensus sequence patterns LxLxL or DLNx(x)P, is found in a... (Review)
Review
The ethylene-responsive element binding factor-associated amphiphilic repression (EAR) motif, defined by the consensus sequence patterns LxLxL or DLNx(x)P, is found in a diverse range of plant species. It is the most predominant form of active transcriptional repression motif identified so far in plants. Despite its small size (5 to 6 amino acids), the EAR motif is primarily involved in the negative regulation of developmental, physiological and metabolic functions in response to abiotic and biotic stresses. Through an extensive literature review, we identified 119 genes belonging to 23 different plant species that contain an EAR motif and function as negative regulators of gene expression in various biological processes, including plant growth and morphology, metabolism and homeostasis, abiotic stress response, biotic stress response, hormonal pathways and signalling, fertility, and ripening. Positive gene regulation and transcriptional activation are studied extensively, but there remains much more to be discovered about negative gene regulation and the role it plays in plant development, health, and reproduction. This review aims to fill the knowledge gap and provide insights into the role that the EAR motif plays in negative gene regulation, and provoke further research on other protein motifs specific to repressors.
Topics: Arabidopsis; Plants, Genetically Modified; Transcription Factors; Amino Acid Motifs; Transcriptional Activation
PubMed: 36833197
DOI: 10.3390/genes14020270 -
Frontiers in Immunology 2023The peptidyl arginine deiminase (PADI) family is a calcium ion-dependent group of isozymes with sequence similarity that catalyze the citrullination of proteins.... (Review)
Review
The peptidyl arginine deiminase (PADI) family is a calcium ion-dependent group of isozymes with sequence similarity that catalyze the citrullination of proteins. Histones can serve as the target substrate of PADI family isozymes, and therefore, the PADI family is involved in NETosis and the secretion of inflammatory cytokines. Thus, the PADI family is associated with the development of inflammatory autoimmune diseases and cancer, reproductive development, and other related diseases. In this review, we systematically discuss the role of the PADI family in the pathogenesis of various diseases based on studies from the past decade to provide a reference for future research.
Topics: Humans; Protein-Arginine Deiminases; Isoenzymes; Autoimmune Diseases; Histones; Neoplasms
PubMed: 37020554
DOI: 10.3389/fimmu.2023.1115794 -
Cureus Jul 2023Colorectal cancer (CRC) is a major global health concern, accounting for significant cancer-related morbidity and mortality worldwide. Despite advancements in early... (Review)
Review
Protective Effects of Long-Term Usage of Cyclo-Oxygenase-2 Inhibitors on Colorectal Cancer in Genetically Predisposed Individuals and Their Overall Effect on Prognosis: A Systematic Review.
Colorectal cancer (CRC) is a major global health concern, accounting for significant cancer-related morbidity and mortality worldwide. Despite advancements in early detection and treatment modalities, the prevention of CRC remains a critical goal. Cyclo-oxygenase-2 (COX-2) is an inducible enzyme involved in the production of pro-inflammatory prostaglandins, which play a crucial role in various cellular processes, including inflammation, cell proliferation, apoptosis, and angiogenesis. Elevated COX-2 expression has been consistently observed in colorectal tumors, indicating their role in the pathogenesis of cancer. COX-2 inhibitors, such as celecoxib and rofecoxib, have been studied as potentially effective treatment modalities due to their ability to decrease prostaglandin levels, which are generally higher in cancer patients. Aberrant prostaglandin production is linked to the adenoma-carcinoma sequence, during which adenomas turn dysplastic and accumulate enough damage to become malignant. COX-2 inhibitors have also been shown to modulate various signaling pathways involved in CRC development, such as wingless-related integration site/β-catenin (Wnt/β-catenin), mitogen-activated protein kinase (MAPK), and phosphoinositide-3-kinase-protein kinase B/Akt (PI3K/Akt) pathways. This systematic review aimed to evaluate the protective effects of long-term usage of COX-2 inhibitors on CRC in genetically predisposed individuals and their overall effect on the prognosis of the disease. The researchers conducted a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines and collected data from several databases, including PubMed, PubMed Central, Cochrane Library, and Web of Science. The search strategy combined keywords related to CRC, COX-2 inhibitors, protective effects, and prognosis. They identified 1189 articles and shortlisted 26 full-text articles that met the eligibility criteria. Quality assessment tools, such as the Assessment of Multiple Systematic Review (AMSTAR) for systematic reviews, the Cochrane bias assessment tool for randomized control trials, the scale for the assessment of narrative review articles (SANRA) checklist for narrative reviews, and the Joanna Briggs Institute (JBI) tool for cross-sectional studies and case reports, are used. This review's conclusions will assist in determining the effectiveness of COX-2 inhibitors to prevent CRC. This review may also contribute to developing guidelines for clinicians to manage genetically predisposed individuals with CRC. Furthermore, the results of this review will shed light on the potential of COX-2 inhibitors as a preventive measure against CRC in genetically predisposed individuals.
PubMed: 37588311
DOI: 10.7759/cureus.41939 -
Clinical Lung Cancer Jan 2024With the widespread application of immune checkpoint inhibitor (ICI) combined with radiotherapy (RT) for the treatment of lung cancer, increasing attention has been paid... (Meta-Analysis)
Meta-Analysis
Effect of Sequence of Radiotherapy Combined With Immunotherapy on the Incidence of Pneumonitis in Patients With Lung Cancer: A Systematic Review and Network Meta-Analysis.
BACKGROUND
With the widespread application of immune checkpoint inhibitor (ICI) combined with radiotherapy (RT) for the treatment of lung cancer, increasing attention has been paid to treatment-related pneumonitis. The effect of the treatment sequence on the incidence of pneumonitis remains unclear.
METHODS
We searched databases including PubMed, Embase, and ClinicalTrials.gov, meeting abstracts, and reference lists of relevant review articles for literature published on radio- and immunotherapy in lung cancer. Stata software (version 16.0) was used for meta-analysis. Data on the incidence of any grade and ≥ grade 3 pneumonitis was pooled using the random effects model. Bayesian network meta-analysis was used for arm-based pairwise comparisons. Subgroup analyses were performed to identify the potential influencing factors.
RESULTS
Thirty-eight studies met our inclusion criteria. The network meta-analysis showed no significant difference between the incidence of pneumonitis in concurrent ICI with RT (concurrent arm) and RT followed by ICI (RT-first arm) (odds ratio [OR]: 0.71, 95% confidence interval [CI]: 0.10-4.81). In the meta-analysis of single group rates, RT following ICI (ICI-first arm) exhibited higher incidence of any grade pneumonitis compared with concurrent- and RT-first arms, with 0.321 (95% CI: 0.260-0.386) for programmed cell death protein 1 (PD-1) inhibitors from clinical trials, and 0.480 (95% CI: 0.363-0.598) for PD-1 inhibitors from real-world retrospective data, respectively.
CONCLUSION
No significant difference in the incidence of any grade and grade ≥ 3 pneumonitis was found between RT-first and concurrent arms. The ICI-first arm exhibited a higher incidence of pneumonitis, which needs to be further confirmed by follow-up studies.
Topics: Humans; Bayes Theorem; Immunotherapy; Incidence; Lung Neoplasms; Network Meta-Analysis; Pneumonia; Retrospective Studies
PubMed: 37612176
DOI: 10.1016/j.cllc.2023.08.008 -
Current Research in Pharmacology and... 2021The outbreak of existing public health distress is threatening the entire world with emergence and rapid spread of severe acute respiratory syndrome coronavirus 2... (Review)
Review
The outbreak of existing public health distress is threatening the entire world with emergence and rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The novel coronavirus disease 2019 (COVID-19) is mild in most people. However, in some elderly people with co-morbid conditions, it may progress to pneumonia, acute respiratory distress syndrome (ARDS) and multi organ dysfunction leading to death. COVID-19 has caused global panic in the healthcare sector and has become one of the biggest threats to the global economy. Drug discovery researchers are expected to contribute rapidly than ever before. The complete genome sequence of coronavirus had been reported barely a month after the identification of first patient. Potential drug targets to combat and treat the coronavirus infection have also been explored. The iterative structure-based drug design (SBDD) approach could significantly contribute towards the discovery of new drug like molecules for the treatment of COVID-19. The existing antivirals and experiences gained from SARS and MERS outbreaks may pave way for identification of potential drug molecules using the approach. SBDD has gained momentum as the essential tool for faster and costeffective lead discovery of antivirals in the past. The discovery of FDA approved human immunodeficiency virus type 1 (HIV-1) inhibitors represent the foremost success of SBDD. This systematic review provides an overview of the novel coronavirus, its pathology of replication, role of structure based drug design, available drug targets and recent advances in in-silico drug discovery for the prevention of COVID-19. SARSCoV- 2 main protease, RNA dependent RNA polymerase (RdRp) and spike (S) protein are the potential targets, which are currently explored for the drug development.
PubMed: 34870145
DOI: 10.1016/j.crphar.2021.100026 -
Annals of Palliative Medicine Apr 2021With the development of new techniques, blood and other humoral biomarkers have become increasingly important in the diagnosis of sepsis-associated acute kidney injury... (Meta-Analysis)
Meta-Analysis
BACKGROUND
With the development of new techniques, blood and other humoral biomarkers have become increasingly important in the diagnosis of sepsis-associated acute kidney injury (AKI). We aimed to review and summarize the biomarkers associated with the diagnosis of sepsis-associated AKI.
METHODS
We performed a systematic review in PubMed, Embase, Web of Science, Cochrane and CNKI literature databases. Chinese and English articles published before January 30, 2021. We extracted information on the sensitivity and specificity of biomarkers to diagnose sepsis-associated AKI, the sample size of individuals with sepsis-associated AKI, the demographic variables, the diagnostic criteria and the sample acquisition protocol. Revman 5.3 software was used to analyze data. The sources of heterogeneity of included studies main were different diagnostic criteria for sepsis and AKI, time of sample collection and Patients came from different departments. We defined the inclusion of related studies by using PICOs (Patient, Intervention, Comparison and Outcome) criteria, in particular the design of studies to be included. P: Patients of sepsis. I: Patients of sepsis-associated AKI. C: Patients without sepsis-associated AKI. O: Diagnosis of sepsis associated kidney injury.
RESULTS
A total of 1,227 articles, including 42 studies, were identified. Increases in urine and serum neutrophil gelatinase-related lipid carrier protein (NGAL), urinary interleukin-18, urinary Kim-1, urinary Netrin-1, urinary sCD163, serum estradiol levels, and serum soluble thrombolytic regulatory protein were most strongly correlated with the diagnosis of sepsis-associated AKI. The SROC of urinary KIM-1 ranked first, followed by the other biomarkers: urinary KIM-1 > urinary NGAL > blood NGAL > urinary IL-18. According to the sample size, the SROC values of urinary NGAL, blood NGAL, urinary IL-18 and urinary KIM-1 were 0.907, 0.857, 0.861 and 0.931, respectively. The sequence was still urinary KIM-1 > urinary NGAL > blood NGAL > urinary IL-18.
CONCLUSIONS
According to the SROC curve area, the diagnostic sequence of sepsis-associated AKI biomarkers was urinary Kim-1 > urinary NGAL > blood NGAL > urinary IL-18. This meta-analysis provided diagnostic features of blood and urine biomarkers based on their association with the diagnosis of sepsis-associated AKI.
Topics: Acute Kidney Injury; Biomarkers; Humans; Lipocalin-2; Sensitivity and Specificity; Sepsis
PubMed: 33832292
DOI: 10.21037/apm-20-1855 -
Journal of Neurochemistry Mar 2021The liver-derived, circulating transport protein transthyretin (TTR) is the cause of systemic hereditary (ATTRv) and wild-type (ATTRwt) amyloidosis. TTR stabilization...
The liver-derived, circulating transport protein transthyretin (TTR) is the cause of systemic hereditary (ATTRv) and wild-type (ATTRwt) amyloidosis. TTR stabilization and knockdown are approved therapies to mitigate the otherwise lethal disease course. To date, the variety in phenotypic penetrance is not fully understood. This systematic review summarizes the current literature on TTR pathophysiology with its therapeutic implications. Tetramer dissociation is the rate-limiting step of amyloidogenesis. Besides destabilizing TTR mutations, other genetic (RBP4, APCS, AR, ATX2, C1q, C3) and external (extracellular matrix, Schwann cell interaction) factors influence the type of onset and organ tropism. The approved small molecule tafamidis stabilizes the tetramer and significantly decelerates the clinical course. By sequence-specific mRNA knockdown, the approved small interfering RNA (siRNA) patisiran and antisense oligonucleotide (ASO) inotersen both significantly reduce plasma TTR levels and improve neuropathy and quality of life compared to placebo. With enhanced hepatic targeting capabilities, GalNac-conjugated siRNA and ASOs have recently entered phase III clinical trials. Bivalent TTR stabilizers occupy both binding groves in vitro, but have not been tested in trials so far. Tolcapone is another stabilizer with the potential to cross the blood-brain barrier, but its half-life is short and liver failure a potential side effect. Amyloid-directed antibodies and substances like doxycycline aim at reducing the amyloid load, however, none of the yet developed antibodies has successfully passed clinical trials. ATTR-amyloidosis has become a model disease for pathophysiology-based treatment. Further understanding of disease mechanisms will help to overcome the remaining limitations, including application burden, side effects, and blood-brain barrier permeability.
Topics: Amyloid; Amyloidosis, Familial; Animals; Gene Knockdown Techniques; Humans; Prealbumin
PubMed: 33155274
DOI: 10.1111/jnc.15233 -
Systematic Reviews May 2020Environmental factors such as pollution, pesticide exposure and socio-demographic location have been implicated as a pressure capable of altering genetic make-up....
Environmental factors such as pollution, pesticide exposure and socio-demographic location have been implicated as a pressure capable of altering genetic make-up. Altered genetic sequence of genes encoding enzymes may result in single nucleotide polymorphism (SNP). Of peculiar interest is the genetic variance on the paraoxonase-1 gene induced by pre- and postnatal exposure to pesticides. SNP have been reported on the paraoxonase-1 gene and post-xenobiotic exposure and are presumed to alter gene sequence and ultimately enzymatic activity. The altered enzymatic activity may facilitate neurodevelopment disorders. Autism spectrum disorders (ASD) and attention deficit hyperactivity disorder (ADHD) are among the neurodevelopment disorders of which prevalence is concurrently associated with increasing environmental xenobiotic exposure. The variance on xenobiotic metabolising genes is associated with altered neurodevelopment outcome and ultimately altered neurobehavioural outcome. Prime interests of this systematic review were to establish an understanding of the sequences on the paraoxonase-1 gene associated with adverse neurobehavioural outcome. An in-depth literature search was conducted using the term combination "pesticide exposure, pre- and postnatal exposure, organophosphates/organophosphorus, single nucleotide polymorphism, paraoxonase-1 (PON-1), neurodevelopment/neurobehavioural outcome in child/infant". Articles published from the year 2000 to 2018 were considered for review. The result showed that variance on the PON1-108 and 192 alleles could be implicated in the development of altered neurobehavioural outcomes.
Topics: Aryldialkylphosphatase; Child; Environmental Exposure; Humans; Organophosphates; Pesticides; Polymorphism, Single Nucleotide
PubMed: 32386510
DOI: 10.1186/s13643-020-01330-9 -
Annals of Palliative Medicine Mar 2022At present, corneal transplantation has become the main surgical method for infectious keratitis. However, the rejection of corneal graft after operation leads to graft... (Meta-Analysis)
Meta-Analysis
BACKGROUND
At present, corneal transplantation has become the main surgical method for infectious keratitis. However, the rejection of corneal graft after operation leads to graft opacity, which is an important reason for the failure of transplantation. There is no unified conclusion whether the rejection can be reduced by matching human leucocyte antigen (HLA) before operation. The purpose of this meta-analysis is to explore the correlation between HLA locus matching and corneal transplantation rejection, so as to provide evidence-based medical evidence for clinical corneal transplantation in the treatment of infectious keratitis.
METHODS
Search English databases, such as PubMed, Medline, Embase and Evidence-based Medicine Library by computer; Chinese databases, such as China Biomedical Literature Database, China Knowledge Network (CNKI) database, Wanfang database, Weipu database, and Google Academic database. According to Cochrane Handbook 5.0 risk assessment table, two researchers made random sequence random allocation method, blind method, allocation scheme hiding, integrity of data results and quality score of research results. The bias risk evaluation of Rev Man 5.3 software was used to evaluate the risk bias of the references.
RESULTS
A total of 5 literatures were included, and 725 eyes underwent penetrating keratoplasty, all of which were randomized controlled trials (RCTs). The quality of the included articles was medium to high quality. A meta-analysis of four HLA-A matching articles showed odds ratio (OR) =0.28, 95% confidential interval (CI): (0.15, 0.51), significance test Z=4.08, P<0.0001, and the difference was statistically significant. Meta-analysis was performed on four HLA-B matching articles and showed OR =0.50, 95% CI: (0.27, 0.89), significance test Z=2.33, P=0.02, and the difference was statistically significant. Meta-analysis of four HLA-DR matching articles showed OR =0.69, 95% CI: (0.41, 1.17), significance test Z=1.39, P=0.17, and the difference was not statistically significant.
DISCUSSION
In patients with infectious keratitis undergoing corneal transplantation, preoperative matching of HLA-A, HLA-B, and HLA-DR sites played an important role in corneal transplantation. Preoperative HLA matching is of clinical significance.
Topics: Amino Acids; Corneal Transplantation; Graft Survival; HLA-DR Antigens; Histocompatibility Testing; Humans
PubMed: 35365041
DOI: 10.21037/apm-22-268