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Archives of Medical Research Feb 2023Gastric cancer (GC) is often diagnosed at an advanced stage and thus patients have a poor prognosis. This implies that early detection of this cancer will improve... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Gastric cancer (GC) is often diagnosed at an advanced stage and thus patients have a poor prognosis. This implies that early detection of this cancer will improve patient prognosis and survival. This systematic review explored the association of circulating protein and metabolite biomarkers with GC development.
METHODS
A literature search was conducted until November 2021 on Medline, Embase, Cochrane library, and Web of Science databases. Studies were included if they assessed circulating proteins and metabolites in blood, urine, or saliva and determined their association with GC risk. Quality of identified studies was determined using the Newcastle-Ottawa scale for cohort studies. Random and fixed effects meta-analyses were performed to calculate pooled odds ratio.
RESULTS
A total of 53 studies were included. High levels of anti-Helicobacter pylORi IgG levels, pepsinogen I (PGI) <30 µg/L and serum pepsinogen I/ pepsinogen II (PGI/II) ratio<3 were positively associated with risk of developing GC (pooled odds ratio (OR): 2.70; 95% CI: 1.44-5.04, 5.96, 95% CI: 2.65-13.42 and 4.43; 95% CI: 3.04-6.47). In addition, an inverse relationship was found between ferritin, iron and transferrin levels and risk of developing GC (OR: 0.62; 95% CI: 0.38-1,0.97; 95% CI: 0.94-1 and 0.85; 95% CI: 0.76-0.94). However, there was no association between levels of glucose, cholesterol, vitamin C, vitamin B12, vitamin A, α-Carotene, β-Carotene, α-Tocopherol, γ-Tocopherol, and GC risk.
CONCLUSION
The pooled analysis demonstrated that high levels of anti-Helicobacter pylORi IgG, PGI<30µg/L and serum PGI/II ratio <3 and low levels of ferritin, iron and transferrin were associated with risk of GC.
Topics: Humans; Stomach Neoplasms; Pepsinogen A; Biomarkers; Pepsinogen C; Immunoglobulin G; Ferritins; Iron; Transferrins; Helicobacter Infections
PubMed: 36759293
DOI: 10.1016/j.arcmed.2022.12.012 -
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 -
Nutrition Reviews Jul 2023Iron deficiency and anemia have serious consequences, especially for children and pregnant women. Iron salts are commonly provided as oral supplements to prevent and... (Meta-Analysis)
Meta-Analysis
The effects of oral ferrous bisglycinate supplementation on hemoglobin and ferritin concentrations in adults and children: a systematic review and meta-analysis of randomized controlled trials.
CONTEXT
Iron deficiency and anemia have serious consequences, especially for children and pregnant women. Iron salts are commonly provided as oral supplements to prevent and treat iron deficiency, despite poor bioavailability and frequently reported adverse side effects. Ferrous bisglycinate is a novel amino acid iron chelate that is thought to be more bioavailable and associated with fewer gastrointestinal (GI) adverse events as compared with iron salts.
OBJECTIVE
A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to evaluate the effects of ferrous bisglycinate supplementation compared with other iron supplements on hemoglobin and ferritin concentrations and GI adverse events.
DATA SOURCES
A systematic search of electronic databases and grey literature was performed up to July 17, 2020, yielding 17 RCTs that reported hemoglobin or ferritin concentrations following at least 4 weeks' supplementation of ferrous bisglycinate compared with other iron supplements in any dose or frequency.
DATA EXTRACTION
Random-effects meta-analyses were conducted among trials of pregnant women (n = 9) and children (n = 4); pooled estimates were expressed as standardized mean differences (SMDs). Incidence rate ratios (IRRs) were estimated for GI adverse events, using Poisson generalized linear mixed-effects models. The remaining trials in other populations (n = 4; men and nonpregnant women) were qualitatively evaluated.
DATA ANALYSIS
Compared with other iron supplements, supplementation with ferrous bisglycinate for 4-20 weeks resulted in higher hemoglobin concentrations in pregnant women (SMD, 0.54 g/dL; 95% confidence interval [CI], 0.15-0.94; P < 0.01) and fewer reported GI adverse events (IRR, 0.36; 95%CI, 0.17-0.76; P < 0.01). We observed a non-significant trend for higher ferritin concentrations in pregnant women supplemented with ferrous bisglycinate. No significant differences in hemoglobin or ferritin concentrations were detected among children.
CONCLUSION
Ferrous bisglycinate shows some benefit over other iron supplements in increasing hemoglobin concentration and reducing GI adverse events among pregnant women. More trials are needed to assess the efficacy of ferrous bisglycinate against other iron supplements in other populations.
PROSPERO REGISTRATION NO
CRD42020196984.
Topics: Adult; Child; Female; Humans; Male; Pregnancy; Anemia, Iron-Deficiency; Dietary Supplements; Ferritins; Hemoglobins; Iron; Iron Deficiencies; Randomized Controlled Trials as Topic; Salts; Ferrous Compounds
PubMed: 36728680
DOI: 10.1093/nutrit/nuac106 -
Clinical and Translational Science Mar 2023Experimental exposure of healthy volunteers to the T-cell dependent neoantigen keyhole limpet hemocyanin (KLH) permits the evaluation of immunomodulatory investigational... (Review)
Review
Experimental exposure of healthy volunteers to the T-cell dependent neoantigen keyhole limpet hemocyanin (KLH) permits the evaluation of immunomodulatory investigational medicinal product (IMP) pharmacology prior to the recruitment of patient populations. Despite widespread use, no standardized approach to the design and conduct of such studies has been agreed. The objective of this systematic review was to survey the published literature where KLH was used as a challenge agent, describing methodology, therapeutic targets addressed, and pharmacodynamic outcome measures. We searched MEDLINE, EMBASE, clinicaltrials.gov, and Cochrane CENTRAL for studies using KLH challenge in humans between January 1, 1994, and April 1, 2022. We described key study features, including KLH formulation, dose, use of adjuvants, route of administration, co-administered IMPs, and end points. Of 2421 titles and abstracts screened, 46 met the inclusion criteria, including 14 (31%) early phase trials of IMP, of which 10 (71%) targeted T-cell co-stimulation. IMPs with diverse mechanisms demonstrated modulation of the humoral response to KLH, suggesting limited specificity of this end point. Two early phase IMP studies (14%) described the response to intradermal re-challenge (delayed type hypersensitivity). Challenge regimens for IMP assessment were often incompletely described, and exhibited marked heterogeneity, including primary KLH dose (25-fold variation: 100-2500 mcg), KLH formulation, and co-administration with adjuvants. Methodological heterogeneity and failure to exploit the access to tissue-level mechanism-relevant end points afforded by KLH challenge has impaired the translational utility of this paradigm to date. Future standardization, characterization, and methodological development is required to permit tailored, appropriately powered, mechanism-dependent study design to optimize drug development decisions.
Topics: Humans; Pharmaceutical Preparations; T-Lymphocytes; Hemocyanins; Adjuvants, Immunologic
PubMed: 36420645
DOI: 10.1111/cts.13457 -
Obesity Reviews : An Official Journal... Jan 2023This study aimed to investigate the prevalence of anemia and related nutrient deficiencies after sleeve gastrectomy (SG). Four online databases were searched for... (Meta-Analysis)
Meta-Analysis Review
This study aimed to investigate the prevalence of anemia and related nutrient deficiencies after sleeve gastrectomy (SG). Four online databases were searched for relevant articles. Thirty-one studies with 7639 patients were included in the meta-analysis. The pooled anemia prevalence was 7%, 6%, 9%, 10%, 12%, 25%, 20%, and 18% at baseline, 3 months, 6 months, 12 months, 24 months, 36 months, 48 months, and 60 months, respectively. Although the prevalence of vitamin B12 and folate deficiencies remained low postoperatively, the prevalence of ferritin deficiency steadily increased from 6% at baseline to 27% at 60 months. The prevalence of serum iron deficiency decreased from 13% at baseline to 6% at 24 months and increased to 20% at 60 months. Anemia and ferritin deficiency were strongly correlated (Pearson correlation coefficient = 0.774, p = 0.041). Subgroup analysis suggested that age ≤40 years, preoperative anemia, and insufficient iron supplementations were high-risk factors for postoperative anemia. SG is associated with an increased risk of anemia and decreased iron storage over long-term observation. Routine iron supplementations may reduce anemia after SG; however, the dosages recommended by current guidelines may be insufficient. More strict monitoring schedules and supplementation strategies should be established for the timely detection and management of postoperative anemia.
Topics: Humans; Adult; Obesity, Morbid; Prevalence; Gastrectomy; Anemia; Ferritins; Iron; Nutrients
PubMed: 36323610
DOI: 10.1111/obr.13516 -
International Journal of Molecular... Oct 2022The characteristic epigenetic profile of periodontitis found in peripheral leukocytes denotes its impact on systemic immunity. In fact, this profile not only stands for... (Review)
Review
The characteristic epigenetic profile of periodontitis found in peripheral leukocytes denotes its impact on systemic immunity. In fact, this profile not only stands for periodontitis as a low-grade inflammatory disease with systemic effects but also as an important source of potentially valuable clinical biomarkers of its systemic effects and susceptibility to other inflammatory conditions. Thus, we aimed to identify relevant genes tested as epigenetic systemic biomarkers in patients with periodontitis, based on the DNA methylation patterns and RNA expression profiles in peripheral immune cells. A detailed protocol was designed following the Preferred Reporting Items for Systematic Review and Meta-analysis -PRISMA guideline. Only cross-sectional and case-control studies that reported potential systemic biomarkers of periodontitis in peripheral immune cell types were included. DNA methylation was analyzed in leukocytes, and gene expression was in polymorphonuclear and mononuclear cells. Hypermethylation was found in TLR regulators genes: , , , , , , and in early stages of periodontitis, while advanced stages presented hypomethylation of these genes. , , , and genes were differentially expressed in lymphocytes and monocytes of subjects with poorly controlled diabetes mellitus, dyslipidemia, and periodontitis in comparison with controls. The gene was differentially overexpressed in periodontitis and dyslipidemia. Peripheral blood neutrophils in periodontitis showed differential expression in 163 genes. Periodontitis showed an increase in ceruloplasmin gene expression in polymorphonuclears in comparison with controls. Several genes highlight the role of the epigenetics of peripheral inflammatory cells in periodontitis that could be explored in blood as a source of biomarkers for routine testing.
Topics: Biomarkers; Ceruloplasmin; Cross-Sectional Studies; DNA Methylation; Dyslipidemias; Gene Expression; Humans; Myeloid Differentiation Factor 88; Periodontitis; RNA
PubMed: 36233348
DOI: 10.3390/ijms231912042 -
BMC Medicine Oct 2022Hormonal changes during the menstrual cycle play a key role in shaping immunity in the cervicovaginal tract. Cervicovaginal fluid contains cytokines, chemokines,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Hormonal changes during the menstrual cycle play a key role in shaping immunity in the cervicovaginal tract. Cervicovaginal fluid contains cytokines, chemokines, immunoglobulins, and other immune mediators. Many studies have shown that the concentrations of these immune mediators change throughout the menstrual cycle, but the studies have often shown inconsistent results. Our understanding of immunological correlates of the menstrual cycle remains limited and could be improved by meta-analysis of the available evidence.
METHODS
We performed a systematic review and meta-analysis of cervicovaginal immune mediator concentrations throughout the menstrual cycle using individual participant data. Study eligibility included strict definitions of the cycle phase (by progesterone or days since the last menstrual period) and no use of hormonal contraception or intrauterine devices. We performed random-effects meta-analyses using inverse-variance pooling to estimate concentration differences between the follicular and luteal phases. In addition, we performed a new laboratory study, measuring select immune mediators in cervicovaginal lavage samples.
RESULTS
We screened 1570 abstracts and identified 71 eligible studies. We analyzed data from 31 studies, encompassing 39,589 concentration measurements of 77 immune mediators made on 2112 samples from 871 participants. Meta-analyses were performed on 53 immune mediators. Antibodies, CC-type chemokines, MMPs, IL-6, IL-16, IL-1RA, G-CSF, GNLY, and ICAM1 were lower in the luteal phase than the follicular phase. Only IL-1α, HBD-2, and HBD-3 were elevated in the luteal phase. There was minimal change between the phases for CXCL8, 9, and 10, interferons, TNF, SLPI, elafin, lysozyme, lactoferrin, and interleukins 1β, 2, 10, 12, 13, and 17A. The GRADE strength of evidence was moderate to high for all immune mediators listed here.
CONCLUSIONS
Despite the variability of cervicovaginal immune mediator measurements, our meta-analyses show clear and consistent changes during the menstrual cycle. Many immune mediators were lower in the luteal phase, including chemokines, antibodies, matrix metalloproteinases, and several interleukins. Only interleukin-1α and beta-defensins were higher in the luteal phase. These cyclical differences may have consequences for immunity, susceptibility to infection, and fertility. Our study emphasizes the need to control for the effect of the menstrual cycle on immune mediators in future studies.
Topics: Elafin; Female; Granulocyte Colony-Stimulating Factor; Humans; Immunoglobulins; Immunologic Factors; Interferons; Interleukin 1 Receptor Antagonist Protein; Interleukin-16; Interleukin-1alpha; Interleukin-6; Interleukins; Lactoferrin; Menstrual Cycle; Muramidase; Progesterone; beta-Defensins
PubMed: 36195867
DOI: 10.1186/s12916-022-02532-9 -
PloS One 2022A wealth of human and experimental studies document a causal and aggravating role of iron deficiency in neurodevelopmental disorders. While pre-, peri-, and early...
BACKGROUND
A wealth of human and experimental studies document a causal and aggravating role of iron deficiency in neurodevelopmental disorders. While pre-, peri-, and early postnatal iron deficiency sets the stage for the risk of developing neurodevelopmental disorders, iron deficiency acquired at later ages aggravates pre-existing neurodevelopmental disorders. Yet, the association of iron deficiency and neurodevelopmental disorders in childhood and adolescence has not yet been explored comprehensively. In this scoping review, we investigate 1) the association of iron deficiency in children and adolescents with the most frequent neurodevelopmental disorders, ADHD, ASD, and FASD, and 2) whether iron supplementation improves outcomes in these disorders.
METHOD
Scoping review of studies published between 1994 and 2021 using "iron deficiency / iron deficiency anemia" AND "ADHD" OR "autism" OR "FASD" in four biomedical databases. The main inclusion criterion was that articles needed to have quantitative determination of iron status at any postnatal age with primary iron markers such as serum ferritin being reported in association with ADHD, ASD, or FASD.
RESULTS
For ADHD, 22/30 studies and 4/4 systematic reviews showed an association of ADHD occurrence or severity with iron deficiency; 6/6 treatment studies including 2 randomized controlled trials demonstrated positive effects of iron supplementation. For ASD, 3/6 studies showed an association with iron deficiency, while 3/6 and 1/1 systematic literature review did not; 4 studies showed a variety of prevalence rates of iron deficiency in ASD populations; 1 randomized controlled trial found no positive effect of iron supplementation on behavioural symptoms of ASD. For FASD, 2/2 studies showed an association of iron deficiency with growth retardation in infants and children with prenatal alcohol exposure.
CONCLUSION
Evidence in favor of screening for iron deficiency and using iron supplementation for pediatric neurodevelopmental disorders comes primarily from ADHD studies and needs to be further investigated for ASD and FASD. Further analysis of study methodologies employed and populations investigated is needed to compare studies against each other and further substantiate the evidence created.
Topics: Adolescent; Anemia, Iron-Deficiency; Child; Female; Ferritins; Humans; Infant; Iron; Iron Deficiencies; Neurodevelopmental Disorders; Pregnancy; Prenatal Exposure Delayed Effects; Randomized Controlled Trials as Topic
PubMed: 36173945
DOI: 10.1371/journal.pone.0273819 -
Revista Brasileira de Ginecologia E... Nov 2022The aim of this study was to systematically review literature on the use of iron supplements (not including iron derived from diet), increased levels of hemoglobin...
OBJECTIVE
The aim of this study was to systematically review literature on the use of iron supplements (not including iron derived from diet), increased levels of hemoglobin and/or ferritin, and the risk of developing gestational diabetes mellitus (GDM).
DATA SOURCE
The following databases were searched, from the study's inception to April 2021: PUBMED, Cochrane, Web of Science, Scopus, Embase, Cinahl and Lilacs.
SELECTION OF STUDIES
A total of 6,956 titles and abstracts were reviewed, 9 of which met the final inclusion criteria, with 7,560 women in total.
DATA COLLECTION
Data extraction was performed by two independent reviewers and disagreements were resolved by a third researcher.
DATA SYNTHESIS
Methodological quality in controlled trials were assessed according to the Cochrane Collaboration tools (ROB-2 and ROBINS-1) and for the observational studies, the National Institutes of Health's (NIH) quality assessment tool was used. Among the 5 observational studies, women with a higher hemoglobin or ferritin level were more likely to develop GDM when compared with those with lower levels of these parameters. Among the 3 randomized clinical trials, none found a significant difference in the incidence of GDM among women in the intervention and control groups. However, we identified many risks of bias and great methodological differences among them.
CONCLUSION
Based on the studies included in this review, and due to the important methodological problems pointed out, more studies of good methodological quality are needed to better establish the association between iron supplementation and GDM.
Topics: United States; Pregnancy; Female; Humans; Diabetes, Gestational; Ferritins; Salts; Iron; Hemoglobins
PubMed: 36067799
DOI: 10.1055/s-0042-1755460 -
American Journal of Clinical Pathology Nov 2022This systematic review investigates reticulocyte hemoglobin's capabilities in screening iron deficiency and iron-deficiency anemia with and without comorbidities. (Meta-Analysis)
Meta-Analysis
OBJECTIVES
This systematic review investigates reticulocyte hemoglobin's capabilities in screening iron deficiency and iron-deficiency anemia with and without comorbidities.
METHODS
Participant background and laboratory characteristics were extracted from 14 unique studies between 2015 and 2022. Hemoglobin, reticulocyte hemoglobin, and mean cell volume (MCV) values were used in a meta-analysis for iron-deficiency anemia with no secondary conditions. Mean laboratory values for each patient population were calculated and then used to determine sensitivity, specificity, and the area under the curve (AUC) for iron deficiency and iron-deficiency anemia. The ferritin and reticulocyte hemoglobin ranges were calculated using the mean values.
RESULTS
The meta-analysis demonstrates that hemoglobin and MCV values do not significantly differ between studies, unlike reticulocyte hemoglobin values. The reticulocyte hemoglobin range is smaller than ferritin for the controls, iron deficiency, and iron-deficiency anemia. Reticulocyte hemoglobin values less than 26 pg can distinguish iron-deficiency anemia, while 26 to 31.5 pg can distinguish iron deficiency, with an AUC of 0.889. The sensitivity and specificity are 92.3% and 100% for iron-deficiency anemia, 100% and 81.5% for iron deficiency, and 94.4% and 71.4% for both, respectively (reference range, <31.5 pg).
CONCLUSIONS
Reticulocyte hemoglobin is potentially a quick screening test for iron deficiency and iron-deficiency anemia.
Topics: Humans; Reticulocytes; Anemia, Iron-Deficiency; Hemoglobins; Iron Deficiencies; Ferritins; Algorithms; Hematology
PubMed: 36048898
DOI: 10.1093/ajcp/aqac103