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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 -
Clinical Nutrition ESPEN Oct 2023Iron deficiency anemia (IDA) is one of the leading causes of anemia, globally. Oral vitamin C enhances iron absorption and is commonly prescribed with iron for anemia... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Iron deficiency anemia (IDA) is one of the leading causes of anemia, globally. Oral vitamin C enhances iron absorption and is commonly prescribed with iron for anemia patients. Considering the lack of evidence to support this practice, we conducted this systematic review and meta-analysis to determine the treatment efficacy of experimental studies where oral vitamin C or ascorbate was given as co-intervention with iron compared to providing only iron among participants with anemia of all ages.
METHODOLOGY
A comprehensive strategy was used to search literature from PubMed, Cochrane and Google Scholar. Experimental studies conducted among participants with lab-confirmed anemia at baseline, with "oral ascorbic acid or vitamin C given as co-intervention with iron" as intervention and "only oral iron" as the comparator, and reported the outcomes hemoglobin or ferritin, were selected. Random-effects model was used to estimate standardized mean differences or odds ratio of outcomes, and sensitivity analyses were done. Sub-group and meta-regression analyses were conducted to evaluate the reasons for heterogeneity (PROSPERO number: CRD42022306612).
RESULTS
Of the total nine studies included in the review, seven studies with 905 participants were included for meta-analysis. The pooled estimate for standardized mean difference (SMD) of hemoglobin (g/dL) and Serum Ferritin (mcg/L) for intervention-type ferrous ascorbate were 0.44 (95% C.I.: -0.30, 1.26) and 0.03 (95% C.I.: -0.68, 0.73) respectively, and were not statistically significant. The pooled estimate for SMD of hemoglobin (g/dL) and Serum Ferritin (mcg/L) for intervention type 'oral iron and vitamin C' was 0.11 (95% C.I.: -0.05, 0.28) and -0.90 (95% C.I.: -1.09, -0.72) respectively, and were not statistically significant.
CONCLUSION
The SMD of hemoglobin or serum ferritin between the intervention group were not significantly favouring the intervention when the intervention group was ferrous ascorbate or oral iron and vitamin C, and the methodological quality of evidence of these effect measures was very low. This necessitates studying the treatment efficacy of oral vitamin C or ascorbate when given with oral iron for participants with anemia in future clinical trials.
Topics: Humans; Ascorbic Acid; Iron; Vitamins; Anemia; Ferritins; Treatment Outcome
PubMed: 37739692
DOI: 10.1016/j.clnesp.2023.07.081 -
Pediatric Neurology Aug 2023Wilson disease (WD) is a hereditary disorder of copper metabolism, caused by mutations in the ATP7B gene. There are more than 1000 pathogenic variants identified in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Wilson disease (WD) is a hereditary disorder of copper metabolism, caused by mutations in the ATP7B gene. There are more than 1000 pathogenic variants identified in ATP7B. R778L is the most common ATP7B mutation in China.
METHODS
To estimate whether R778L is associated with the onset age of WD and other clinical variables. Genotyping results of ATP7B gene were collected in our 22 patients with WD. We then conducted a systematic review and meta-analysis in databases, using the keywords Wilson disease and R778L mutation.
RESULTS
After the screening, a total of 23 studies were included, including 3007 patients with WD. Patients with R778L mutation presented at an earlier age (standardized mean difference [SMD] = -0.18 [95% confidence interval, -0.28 to 0.08], P = 0.0004) and had lower ceruloplasmin concentration (SMD = -0.21 [95% confidence interval, -0.40 to -0.02], P = 0.03) than the patients without the R778L mutation. However, sex (odds ratio [OR] = 1.07 [95% confidence interval, 0.89 to 1.29], P = 0.32) and first presentation were not associated with R778L mutation in WD (hepatic: OR = 1.37 [95% confidence interval, 0.87 to 2.16, P = 0.17; neurological: OR = 0.79 [95% confidence interval, 0.48 to 1.30, P = 0.35; mix: OR = 1.04 [95% confidence interval, 0.42 to 2.53, P = 0.87; asymptomatic/others: OR = 1.98 [95% confidence interval, 0.49 to 7.96, P = 0.34).
CONCLUSIONS
Our results indicated that the R778L mutation is associated with an earlier presentation and lower ceruloplasmin concentration in China.
Topics: Humans; Ceruloplasmin; China; Copper-Transporting ATPases; Hepatolenticular Degeneration; Mutation
PubMed: 37354629
DOI: 10.1016/j.pediatrneurol.2023.04.026 -
Journal of Human Lactation : Official... Aug 2022Human colostrum has been used in a number of investigations when preterm human infants cannot, for any reason, breastfeed directly from their mothers. One of the growing... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Human colostrum has been used in a number of investigations when preterm human infants cannot, for any reason, breastfeed directly from their mothers. One of the growing fields in these investigations is colostrum therapy, which consists of exposing the oropharyngeal mucosa of these preterm newborns to small amounts of raw colostrum.
RESEARCH AIM
To critically review the scientific evidence about colostrum therapy in premature infants and to explore its influences on the immune system.
METHODS
This systematic review was performed according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA statement). The following databases were searched for potentially eligible studies up to March 10, 2021: Medline, Scopus, Web of Science, Cochrane Library, Embase. Two reviewers independently screened all titles, abstracts, and full texts for eligibility.
RESULTS
A total of 12 studies with 996 participants were included. A significant difference in lactoferrin levels in the urine was found ( 0.70; 95% CI [0.03,1.36]; = .04; ² = 65% two studies, 112 participants, very low-quality evidence).
CONCLUSION
Colostrum seems to result in increasing lactoferrin levels in the urine of premature newborns after 1 week of intervention.
CLINICAL TRIAL REGISTRATION
The study was registered at PROSPERO with the number CRD42017073624, submitted on August 9, 2017.
Topics: Breast Feeding; Colostrum; Female; Humans; Immune System; Infant; Infant, Newborn; Infant, Premature, Diseases; Lactoferrin; Pregnancy
PubMed: 35416063
DOI: 10.1177/08903344221087967 -
PloS One 2022Roxadustat (ROX) is a new medication for anemia as a complication of chronic kidney disease (CKD). Our meta-analysis aims to evaluate the efficacy and safety of ROX,... (Meta-Analysis)
Meta-Analysis
The efficacy and safety of roxadustat for the treatment of anemia in non-dialysis dependent chronic kidney disease patients: An updated systematic review and meta-analysis of randomized clinical trials.
BACKGROUND
Roxadustat (ROX) is a new medication for anemia as a complication of chronic kidney disease (CKD). Our meta-analysis aims to evaluate the efficacy and safety of ROX, especially on the cardiovascular risks, for anemia in NDD-CKD patients.
METHODS
Electronic databases were searched systematically from inception to July 2021 to look for randomized control trials (RCTs) that evaluated ROX NDD-CKD patients. Hemoglobin level and iron utilization parameters, including ferritin, serum iron, transferrin saturation (TSAT), total iron-binding capacity (TIBC), transferrin, and hepcidin were analyzed for efficacy. Pooled risk ratios (RRs) and standardized mean differences (SMDs) were calculated and presented with their 95% confidential intervals (CIs).
RESULTS
Nine RCTs included a total of 3,175 patients in the ROX group and 2,446 patients in the control group. When compared the control group, ROX increased Hb level significantly (SMD: 1.65; 95% CI: 1.08, 2.22; P< 0.00001) and improved iron utilization parameters by decreasing ferritin (SMD: -0.32; 95% CI: -0.51, -0.14; P = 0.0006), TSAT (SMD: -0.19; 95% CI: -0.32, -0.07; P = 0.003), and hepcidin (SMD: -0.74; 95% CI: -1.09, -0.39; P< 0.0001) and increasing TIBC (SMD: 0.99; 95% CI: 0.76, 1.22; P< 0.00001) and transferrin (SMD: 1.20; 95% CI: 0.70, 1.71; P< 0.00001). As for safety, ROX was associated with higher serious adverse effects (RR: 1.07; 95% CI: 1.01, 1.13; P = 0.01), deep venous thrombosis (DVT) (RR: 3.80; 95% CI: 1.5, 9.64; P = 0.08), and hypertension (HTN) (RR: 1.37; 95% CI: 1.13, 1.65; P = 0.001).
CONCLUSION
We concluded that ROX increased Hb level and improved iron utilization parameters in NDD-CKD patients, but ROX was associated with higher serious adverse effects, especially DVT and HTN. Our results support the use of ROX for NDD-CKD patients with anemia. However, higher-quality RCTs are still needed to ensure its safety and risk of thrombosis.
Topics: Anemia; Ferritins; Glycine; Hepcidins; Humans; Iron; Isoquinolines; Randomized Controlled Trials as Topic; Renal Insufficiency, Chronic; Transferrin
PubMed: 35363823
DOI: 10.1371/journal.pone.0266243 -
Iranian Journal of Allergy, Asthma, and... Dec 2020Several reports have determined that changes in white blood cell counts and inflammatory biomarkers are related to disease outcome of coronavirus disease 2019 (COVID-19)... (Meta-Analysis)
Meta-Analysis
Several reports have determined that changes in white blood cell counts and inflammatory biomarkers are related to disease outcome of coronavirus disease 2019 (COVID-19) and they can be utilized as prognostic biomarkers. For introducing a factor as a diagnostic/prognostic biomarker, diagnostic test accuracy (DTA) systematic review and meta-analysis are recommended. For the first time, we aimed to determine the accuracies of white blood cell counts and inflammatory biomarkers for prognosis of COVID-19 patient's outcome by a DTA meta-analysis. Until August24, 2020, we searched Web of Sciences, Scopus, and MEDLINE/PubMed databases to achieve related papers. Summary points and lines of included studies were calculated from 2×2 tables by bivariate/hierarchical models. Critical condition and mortality were considered as outcomes. A total of 13387 patients from 28 studies were included in this study. Six biomarkers containing leukocytosis, neutrophilia, lymphopenia, increased level of C-reactive protein, procalcitonin (PCT), and ferritin met the inclusion criteria. Analysis of the area under the curve (AUCHSROC) indicated that the PCT was the only applicable prognostic biomarker for critical condition and mortality (AUCHSROC=0.80 for both conditions). Pooled-diagnostic odds ratios were 6.78 (95% CI, 3.65-12.61) for prognosis of critical condition and 13.21 (95% CI, 3.95-44.19) for mortality. Other biomarkers had insufficient accuracies for both conditions (AUCHSROC< 0.80). Among evaluated biomarkers, only PCT has good accuracy for the prognosis of both critical condition and mortality in COVID-19 and it can be considered as a single prognostic biomarker for poor outcomes. Also, PCT has more accuracy for the prognosis of mortality in comparison to critical condition.
Topics: Area Under Curve; C-Reactive Protein; COVID-19; Critical Illness; Ferritins; Humans; Hyperferritinemia; Leukocytosis; Lymphopenia; Neutrophils; Procalcitonin; Prognosis; ROC Curve; SARS-CoV-2; Severity of Illness Index
PubMed: 33463126
DOI: 10.18502/ijaai.v19i6.4926 -
The Cochrane Database of Systematic... Nov 2019Wilson's disease, first described by Samuel Wilson in 1912, is an autosomal recessive metabolic disorder resulting from mutations in the ATP7B gene. The disease develops... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Wilson's disease, first described by Samuel Wilson in 1912, is an autosomal recessive metabolic disorder resulting from mutations in the ATP7B gene. The disease develops as a consequence of copper accumulating in affected tissues. There is no gold standard for the diagnosis of Wilson's disease, which is often delayed due to the non-specific clinical features and the need for a combination of clinical and laboratory tests for diagnosis. This delay may in turn affect clinical outcome and has implications for other family members in terms of diagnosis. The Leipzig criteria were established to help standardise diagnosis and management. However, it should be emphasised that these criteria date from 2003, and many of these have not been formally evaluated; this review examines the evidence behind biochemical testing for Wilson's disease.
OBJECTIVES
To determine the diagnostic accuracy of three biochemical tests at specified cut-off levels for Wilson's disease. The index tests covered by this Cochrane Review are caeruloplasmin, 24-hour urinary copper and hepatic copper content. These tests were evaluated in those with suspected Wilson's disease and appropriate controls (either healthy or those with chronic liver disease other than Wilson's). In the absence of a gold standard for diagnosing Wilson's disease, we have used the Leipzig criteria as a clinical reference standard. To investigate whether index tests should be performed in all individuals who have been recommended for testing for Wilson's disease, or whether these tests should be limited to subgroups of individuals.
SEARCH METHODS
We identified studies by extensive searching of, e.g. the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase, the Web of Science and clinical trial registries (29 May 2019). Date of the most recent search of the Cochrane Cystic Fibrosis and Genetic Disorders Inborn Errors of Metabolism Register: 29 May 2019.
SELECTION CRITERIA
We included prospective and retrospective cohort studies that assessed the diagnostic accuracy of an index test using the Leipzig criteria as a clinical reference standard for the diagnosis of Wilson's disease.
DATA COLLECTION AND ANALYSIS
Two review authors independently reviewed and extracted data and assessed the methodological quality of each included study using the QUADAS-2 tool. We had planned to undertake meta-analyses of the sensitivity, specificity at relevant cut-offs for each of the biochemical tests for Wilson's, however, due to differences in the methods used for each biochemical index test, it was not possible to combine the results in meta-analyses and hence these are described narratively.
MAIN RESULTS
Eight studies, involving 5699 participants (which included 1009 diagnosed with Wilson's disease) were eligible for inclusion in the review. Three studies involved children only, one adults only and the four remaining studies involved both children and adults. Two evaluated participants with hepatic signs and six with a combination of hepatic and neurological signs and symptoms of Wilson's disease, as well as pre-symptomatic individuals. The studies were of variable methodological quality; with high risk if bias for participant selection and the reference standard used being of greatest methodological concern. Key differences between studies include differences in assay methodology, different cut-off values for diagnostic thresholds, different age and ethnicity groups. Concerns around study design imply that diagnostic accuracy figures may not transfer to populations outside of the relevant study.
INDEX TEST
caeruloplasmin Five studies evaluated various thresholds of caeruloplasmin (4281 participants, of which 541 had WD). For caeruloplasmin a cut-off of 0.2 g/L as in the Leipzig criteria achieved a sensitivity of 77.1% to 99%, with variable specificity of 55.9% to 82.8%. Using the cut-off of 0.1 g/L of the Leipzig criteria seemed to lower the sensitivity overall, 65% to 78.9%, while increasing the specificity to 96.6% to 100%.
INDEX TEST
hepatic copper Four studies evaluated various thresholds of hepatic copper (1150 participants, of which 367 had WD). The hepatic copper cut-off of 4 μmol/g used in the Leipzig criteria achieved a sensitivity of 65.7% to 94.4%, with a variable specificity of 52.2% to 98.6%.
INDEX TEST
24-hour urinary copper Three studies evaluated various thresholds of 24-hour urinary copper (268 participants, of which 101 had WD). For 24-hour urinary copper, a cut-off of 0.64 to 1.6 μmol/24 hours used in the Leipzig criteria achieved a variable sensitivity of 50.0% to 80.0%, with a specificity of 75.6% to 98.3%.
AUTHORS' CONCLUSIONS
The cut-offs used for caeruloplasmin, 24-hour urinary copper and hepatic copper for diagnosing Wilson's disease are method-dependent and require validation in the population in which such index tests are going to be used. Binary cut-offs and use of single-test strategies to rule Wilson's disease in or out is not supported by the evidence in this review. There is insufficient evidence to inform testing in specific subgroups, defined by age, ethnicity or clinical subgroups.
Topics: Biomarkers; Ceruloplasmin; Copper; Hepatolenticular Degeneration; Humans; Liver; Randomized Controlled Trials as Topic
PubMed: 31743430
DOI: 10.1002/14651858.CD012267.pub2 -
BMC Oral Health Mar 2024Recurrent Aphthous Stomatitis (RAS) known as recurrent aphthous ulcer is a common and painful ulcerations in oral cavity. It has been suggested that hematological... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Recurrent Aphthous Stomatitis (RAS) known as recurrent aphthous ulcer is a common and painful ulcerations in oral cavity. It has been suggested that hematological parameters seems to be considered as an etiologic factor. So, this meta-analysis and systematic review was aimed to examine the relationship between RAS and hematological parameters.
METHODS
Relevant studies were found using online international databases including Scopus, Science direct, Web of science (ISI), PubMed, and Google Scholar search engine between 2000 and October 2023. The quality of all papers was determined by NOS checklist. Heterogeneity between the results of primary studies was evaluated with I-square index and publication bias was performed by Egger's test and funnel plots. Also, sensitivity analysis was done to check the effect of each of the primary studies on the overall estimate. Also, the statistical analyses were done using Stata software Ver. 11.
RESULTS
By combining the results of primary studies, the standardized mean difference (SMD) of vitamin B12, ferritin, folic acid, hemoglobin, iron and zinc indices with a 95% confidence interval (CI) between the case (patients with RAS) and control (Healthy) groups were estimated -0.52(-0.89, -0.14), -0.20(-0.51, 0.11), -0.42(-0.95, 0.11), -0.58(-0.90, -0.27), 0.01(-0.12, 0.15), -0.33(-0.81, 0.14) respectively. The patients with vitamin B12, ferritin, folic acid, and iron deficiencies and reduced hemoglobin (Hb) level reported 2.93(2.28, 3.78), 2.50(1.48, 4.22), 1.51(0.53, 4.29), 1.46(0.70, 3.03), and 2.14(1.38, 3.32), times more susceptible to develop RAS than healthy individuals.
CONCLUSION
The results of the meta-analysis indicated that the SMD of vitamin B12 serum and Hb levels in the case group was 52%. Our result have also showed that the odds ratio of vitamin B12, ferritin deficiencies, and decreased Hb level in case group was 2.93, 2.50, and 2.14 times more than healthy group.
Topics: Humans; Stomatitis, Aphthous; Vitamin B 12 Deficiency; Folic Acid Deficiency; Folic Acid; Vitamin B 12; Hemoglobins; Ferritins
PubMed: 38493289
DOI: 10.1186/s12903-024-04072-5 -
The British Journal of Nutrition Jan 2023Inflammation and infections such as malaria affect estimates of micronutrient status. Medline, Embase, Web of Science, Scopus and the Cochrane library were searched to... (Meta-Analysis)
Meta-Analysis Review
Inflammation and infections such as malaria affect estimates of micronutrient status. Medline, Embase, Web of Science, Scopus and the Cochrane library were searched to identify studies reporting mean concentrations of ferritin, hepcidin, retinol or retinol binding protein in individuals with asymptomatic or clinical malaria and healthy controls. Study quality was assessed using the US National Institute of Health tool. Random effects meta-analyses were used to generate summary mean differences. In total, forty-four studies were included. Mean ferritin concentrations were elevated by: 28·2 µg/l (95 % CI 15·6, 40·9) in children with asymptomatic malaria; 28·5 µg/l (95 % CI 8·1, 48·8) in adults with asymptomatic malaria; and 366 µg/l (95 % CI 162, 570) in children with clinical malaria compared with individuals without malaria infection. Mean hepcidin concentrations were elevated by 1·52 nmol/l (95 % CI 0·92, 2·11) in children with asymptomatic malaria. Mean retinol concentrations were reduced by: 0·11 µmol/l (95 % CI -0·22, -0·01) in children with asymptomatic malaria; 0·43 µmol/l (95 % CI -0·71, -0·16) in children with clinical malaria and 0·73 µmol/l (95 % CI -1·11, -0·36) in adults with clinical malaria. Most of these results were stable in sensitivity analyses. In children with clinical malaria and pregnant women, difference in ferritin concentrations were greater in areas with higher transmission intensity. We conclude that biomarkers of iron and vitamin A status should be statistically adjusted for malaria and the severity of infection. Several studies analysing asymptomatic infections reported elevated ferritin concentrations without noticeable elevation of inflammation markers, indicating a need to adjust for malaria status in addition to inflammation adjustments.
Topics: Child; Adult; Humans; Female; Pregnancy; Iron; Vitamin A; Hepcidins; Vitamin A Deficiency; Nutritional Status; Malaria; Ferritins; Anemia, Iron-Deficiency; Inflammation
PubMed: 35260210
DOI: 10.1017/S0007114522000757 -
Critical Reviews in Food Science and... 2022Lactoferrin (Lf), a bioactive protein initially found in many biological secretions including milk, is regarded as the nutritional supplement or therapeutic ligand due...
Lactoferrin (Lf), a bioactive protein initially found in many biological secretions including milk, is regarded as the nutritional supplement or therapeutic ligand due to its multiple functions. Research on its mode of action reveals that intact Lf or its active peptide (i.e., lactoferricin) shows an important multifunctional performance. Oral delivery is considered as the most convenient administration route for this bioactive protein. Unfortunately, Lf is sensitive to the gastrointestinal (GI) physicochemical stresses and lactoferricin is undetectable in GI digesta. This review introduces the functionality of Lf at the molecular level and its degradation behavior in GI tract is discussed in detail. Subsequently, the absorption and transport of Lf from intestine into the blood circulation, which is pivotal to its health promoting effects in various tissues, and some assisting labeling methods are discussed. Stabilization technologies aiming at preserving the structural integrity and functional properties of orally administrated Lf are summarized and compared. Altogether, this work comprehensively reviews the structure-function relationship of Lf, its oral fate and the development of stabilization technologies for the enhancement of the oral bioavailability of Lf. The existing limitations and scope for future research are also discussed.
Topics: Animals; Chemical Phenomena; Gastrointestinal Tract; Lactoferrin; Milk
PubMed: 33749401
DOI: 10.1080/10408398.2021.1900774