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Advances in Therapy Dec 2019Leber's hereditary optic neuropathy (LHON) is a relatively common, rapidly progressing inherited optic neuropathy wherein LHON-affected eyes undergo optic nerve atrophy...
Leber's hereditary optic neuropathy (LHON) is a relatively common, rapidly progressing inherited optic neuropathy wherein LHON-affected eyes undergo optic nerve atrophy due to retinal ganglion cell (RGC) loss. It is a maternally inherited (or sporadic) mitochondrial disorder caused primarily by mutations in genes that encode components of respiratory complex (RC)1 in mitochondria. Mitochondrial deficiency of RC1 compromises ATP production and oxidative stress management in RGCs. The most common LHON-causing mutations are 11778G>A, 3460G>A, and 14484T>C point mutations in MT-ND4, MT-ND1, and MT-ND6. The unusually high mitochondrial load of RGCs makes them particularly sensitive to these mutations. Patients with LHON may be prescribed ubiquinone (a component of RC3) or idebenone, a ubiquinone analogue with enhanced bioavailability to act downstream of RC1. The challenge of accessing the inner mitochondrial membrane with gene therapy for LHON, and other mitochondrial diseases, may be overcome by incorporation of a specific mitochondrion-targeting sequence (MTS) that enables allotropic expression of a nucleus-transcribed ND4 transgene. Because LHON penetrance is incomplete among carriers of the aforementioned mutations, identification of environmental factors, such as heavy smoking, that interact with genetics in the phenotypic expression of LHON may be helpful toward preventing or delaying disease development. LHON has become a model for mitochondrial and neurogenerative diseases owing to it having a clearly identified genetic cause and its early onset and rapid progression characteristics. Hence, LHON studies and genetic treatment advances may inform research of other diseases.
Topics: DNA, Mitochondrial; Electron Transport Complex I; Genetic Therapy; Humans; Mutation; Optic Atrophy, Hereditary, Leber; Phenotype; Point Mutation
PubMed: 31605306
DOI: 10.1007/s12325-019-01113-2 -
Nutrients Jan 2022Ferrous sulfate is a commonly used iron supplement for the correction of iron-deficiency anemia but with frequent gastrointestinal side effects. Milk-derived... (Meta-Analysis)
Meta-Analysis
Ferrous sulfate is a commonly used iron supplement for the correction of iron-deficiency anemia but with frequent gastrointestinal side effects. Milk-derived iron-binding glycoprotein lactoferrin possesses well gastrointestinal tolerance and fewer side effects caused by the intake of high-dose iron. However, the underlying mechanism of the iron-enhancing effect of lactoferrin remains unclear. In addition, the comparative efficacies between lactoferrin and ferrous sulfate are also remained to be determined. We conducted a systematic review and meta-analysis on published intervention studies to investigate how lactoferrin modulate iron metabolism and evaluate the comparative effects between lactoferrin and ferrous sulfate supplementation on iron absorption, iron storage, erythropoiesis and inflammation. Lactoferrin supplementation had better effects on serum iron (WMD: 41.44 ug/dL; p < 0.00001), ferritin (WMD: 13.60 ng/mL; p = 0.003) and hemoglobin concentration (11.80 g/dL; p < 0.00001), but a reducing effect on fractional iron absorption (WMD: −2.08%; p = 0.02) and IL-6 levels (WMD: −45.59 pg/mL; p < 0.00001) compared with ferrous sulfate. In conclusion, this study supports lactoferrin as a superior supplement to ferrous sulfate regarding the improvement in serum iron parameters and hemoglobin levels. Considering the weak influence of lactoferrin on iron absorption, the anti-inflammation effect of lactoferrin may be the potential mechanism to explain its efficacy on iron status and erythropoiesis.
Topics: Anemia, Iron-Deficiency; Clinical Trials as Topic; Dietary Supplements; Ferrous Compounds; Humans; Lactoferrin
PubMed: 35276902
DOI: 10.3390/nu14030543 -
Bioscience Reports Jun 2020The improvement of malnutrition with levocarnitine in maintenance hemodialysis (MHD) patients is controversial. We performed a meta-analysis to evaluate the efficacy of... (Meta-Analysis)
Meta-Analysis
The improvement of malnutrition with levocarnitine in maintenance hemodialysis (MHD) patients is controversial. We performed a meta-analysis to evaluate the efficacy of levocarnitine in improving malnutrition in MHD patients. We performed a literature search for relevant articles related to the treatment of malnutrition by L-carnitine in MHD patients in PubMed, Embase, Web of Science, China National Knowledge Infrastructure, and Wanfang databases. We set the publication dates from 1950 to July 2019. The levels of albumin, prealbumin, total protein, and transferrin before and after treatment were used for assessing malnutrition. Twenty-seven studies were included in the present analysis. The results of the random effects model indicated that L-carnitine treatment improved the albumin level in patients on MHD patients. The pooled standardized mean difference of albumin level was 2.51 (95% confidence interval (CI): 2.13-2.90, P<0.001). The pooled total protein level was 3.83 (95% CI: 2.41-5.24, P = 0.000) and the pooled transferrin level was 0.35 (95% CI: 0.18-0.52, P = 0.000). Significant differences were observed with the total protein and transferrin levels. The results indicated that levocarnitine significantly improved the prealbumin level in patients on MHD. The pooled prealbumin level was 70.86 (95% CI: 42.99-98.73, P = 0.000). No publication bias was detected (P>0.05). The present meta-analysis indicated that L-carnitine can have a favorable effect on malnutrition biomarkers in patients on MHD, including the increase in albumin, total protein, transferrin, and prealbumin levels. The L-carnitine could be an option for treatment of MHD patients.
Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Carnitine; Dietary Supplements; Female; Humans; Kidney Diseases; Male; Malnutrition; Middle Aged; Nutritional Status; Prealbumin; Renal Dialysis; Serum Albumin, Human; Transferrin; Treatment Outcome
PubMed: 32490516
DOI: 10.1042/BSR20201639 -
Journal of Medical Virology Jul 2021To conduct a systematic review and meta-analysis to characterize inflammatory markers in comparisons of multisystem inflammatory syndrome in children (MIS-C) versus... (Meta-Analysis)
Meta-Analysis
To conduct a systematic review and meta-analysis to characterize inflammatory markers in comparisons of multisystem inflammatory syndrome in children (MIS-C) versus severe/non-severe COVID-19, severe MIS-C versus non-severe MIS-C, and among age groups of MIS-C. Nine databases were searched for studies on inflammatory markers of MIS-C. After quality checks, data were pooled using a fixed or random effects model. Inflammatory markers included white blood cell count (WBC) or leukocytes, absolute lymphocyte count (ALC), absolute neutrophil count (ANC), platelet count (PLT), C-reactive protein (CRP), procalcitonin (PCT), ferritin, D-dimer, lactate dehydrogenase (LDH), fibrinogen, and erythrocyte sedimentation rate (ESR) for comparisons by severity and age. Twenty-one studies with 1735 participants yielded 787 MIS-C patients. Compared to non-severe COVID-19 patients, MIS-C patients had lower ALC and higher ANC, CRP, and D-dimer levels. Compared to severe COVID-19 patients, MIS-C patients had lower LDH and PLT counts and higher ESR levels. Severe MIS-C patients had higher levels of WBC, ANC, CRP, D-dimer, and ferritin than non-severe MIS-C patients. For MIS-C, younger children (0-5 years) had lower CRP and ferritin levels than middle-aged/older children/adolescents. Measurement of inflammatory markers might assist clinicians in accurate evaluation and diagnosis of MIS-C and the associated disorders.
Topics: Adolescent; Biomarkers; Blood Sedimentation; C-Reactive Protein; COVID-19; Child; Child, Preschool; Ferritins; Fibrin Fibrinogen Degradation Products; Fibrinogen; Humans; Infant; Infant, Newborn; L-Lactate Dehydrogenase; Leukocyte Count; Lymphocyte Count; Lymphocytes; Neutrophils; Platelet Count; Procalcitonin; SARS-CoV-2; Systemic Inflammatory Response Syndrome; Young Adult
PubMed: 33739452
DOI: 10.1002/jmv.26951 -
Journal of Critical Care Feb 2022Ferritin is a known inflammatory biomarker in COVID-19. However, many factors and co-morbidities can confound the level of serum ferritin. This current metaanalysis... (Meta-Analysis)
Meta-Analysis
Ferritin is a known inflammatory biomarker in COVID-19. However, many factors and co-morbidities can confound the level of serum ferritin. This current metaanalysis evaluates serum ferritin level in different severity levels in COVID-19. Studies evaluating serum ferritin level in different clinical contexts (COVID-19 vs. control, mild to moderate vs. severe to critical, non-survivor vs. survivor, organ involvement, ICU and mechanical ventilation requirement) were included (total 9 literature databases searched). Metaanalysis and metaregression was carried out using metaphor "R" package. Compared to control (COVID-19 negative), higher ferritin levels were found among the COVID-19 patients [SMD -0.889 (95% C.I. -1.201, -0.577), I = 85%]. Severe to critical COVID-19 patients showed higher ferritin levels compared to mild to moderate COVID-19 patients [SMD 0.882 (0.738, 1.026), I = 85%]. In meta-regression, high heterogeneity was observed could be attributed to difference in "mean age", and "percentage of population with concomitant co-morbidities". Non-survivors had higher serum ferritin level compared to survivors [SMD 0.992 (0.672, 1.172), I = 92.33%]. In meta-regression, high heterogeneity observed could be attributed to difference in "mean age" and "percentage of male sex". Patients requiring ICU [SMD 0.674 (0.515 to 0.833), I = 80%] and mechanical ventilation [SMD 0.430 (0.258, 0.602), I = 32%] had higher serum ferritin levels compared to those who didn't. To conclude, serum ferritin level may serve as an important biomarker which can aid in COVID-19 management. However, presence of other co-morbid conditions/confounders warrants cautious interpretation.
Topics: Biomarkers; COVID-19; Ferritins; Humans; Regression Analysis
PubMed: 34808527
DOI: 10.1016/j.jcrc.2021.09.023 -
International Journal of Molecular... Jul 20215-Lipoxygenase (5-LOX) plays a key role in inflammation through the biosynthesis of leukotrienes and other lipid mediators. Current evidence suggests that dietary...
5-Lipoxygenase (5-LOX) plays a key role in inflammation through the biosynthesis of leukotrienes and other lipid mediators. Current evidence suggests that dietary (poly)phenols exert a beneficial impact on human health through anti-inflammatory activities. Their mechanisms of action have mostly been associated with the modulation of pro-inflammatory cytokines (TNF-α, IL-1β), prostaglandins (PGE), and the interaction with NF-κB and cyclooxygenase 2 (COX-2) pathways. Much less is known about the 5-lipoxygenase (5-LOX) pathway as a target of dietary (poly)phenols. This systematic review aimed to summarize how dietary (poly)phenols target the 5-LOX pathway in preclinical and human studies. The number of studies identified is low (5, 24, and 127 human, animal, and cellular studies, respectively) compared to the thousands of studies focusing on the COX-2 pathway. Some (poly)phenolics such as caffeic acid, hydroxytyrosol, resveratrol, curcumin, nordihydroguaiaretic acid (NDGA), and quercetin have been reported to reduce the formation of 5-LOX eicosanoids in vitro. However, the in vivo evidence is inconclusive because of the low number of studies and the difficulty of attributing effects to (poly)phenols. Therefore, increasing the number of studies targeting the 5-LOX pathway would largely expand our knowledge on the anti-inflammatory mechanisms of (poly)phenols.
Topics: Animals; Anti-Inflammatory Agents; Humans; Inflammation; Lipoxygenase; Lipoxygenase Inhibitors; Phenols; Polyphenols
PubMed: 34360703
DOI: 10.3390/ijms22157937 -
Digestion 2021The need for noninvasive markers of disease activity is mandatory in the assessment of Crohn's disease (CD). The most widely fecal biomarker in CD, despite several...
INTRODUCTION
The need for noninvasive markers of disease activity is mandatory in the assessment of Crohn's disease (CD). The most widely fecal biomarker in CD, despite several limits, is fecal calprotectin. This review aims to elucidate the role, if any, of all other fecal biomarkers, as alternative tools for assessing clinical and endoscopic disease activity, and predict capsule endoscopy findings, response to therapy, disease relapse, and postoperative recurrence. These fecal biomarkers included lactoferrin, S100A12, high mobility group box 1, neopterin, polymorphonuclear neutrophil elastase, fecal hemoglobin, alpha1-antitrypsin, lysozyme, human beta-defensin-2, neutrophil gelatinase-associated lipocalin, matrix metalloproteinase-9, chitinase 3-like-1, M2-pyruvate kinase, myeloperoxidase, and eosinophil proteins.
METHODS
A systematic electronic search in the medical literature was performed up to April 2020. Seventy eligible studies were identified out of 859 citations. Data were grouped according to the assessment of clinical and endoscopic disease activity, capsule endoscopy findings, response to therapy, prediction of relapse, and postoperative recurrence.
RESULTS
The overall correlation between lactoferrin and clinical indexes is poor, while performance is good with endoscopic scores. Lactoferrin seems to represent a reasonably good surrogate marker of response to therapy and to be potentially useful in identifying patients at high risk for endoscopic relapse or postoperative recurrence. The evaluation of the performance of all other fecal markers is limited by the lack of adequate data.
CONCLUSIONS
None of the fecal markers so far represents an acceptable alternative to calprotectin in clinical practice. Fecal lactoferrin is the only possible exception, but a more extensive investigation is still required.
Topics: Biomarkers; Crohn Disease; Feces; Humans; Lactoferrin; Leukocyte L1 Antigen Complex; Severity of Illness Index
PubMed: 34518458
DOI: 10.1159/000518419 -
Medicine Nov 2019The family of tripartite motif (TRIM) proteins, which includes 80 known TRIM protein genes in humans, play a key role in cellular processes. TRIM59, a member of the TRIM... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The family of tripartite motif (TRIM) proteins, which includes 80 known TRIM protein genes in humans, play a key role in cellular processes. TRIM59, a member of the TRIM family of proteins, has been reported to be involved in the carcinogenesis of multiple types of tumors. However, the prognostic value of TRIM59 in the survival of tumor patients remains controversial. We therefore conducted a meta-analysis to assess the prognostic significance of TRIM59 in cancer patients.
MATERIALS AND METHODS
PubMed, Embase, VIP, CNKI and Wanfang Data were searched for eligible reports published before September 30, 2018. The hazard ratio (HR) and 95% confidence intervals (CIs) were adopted to estimate the association between TRIM59 and overall survival (OS).
RESULTS
Six studies with 1584 patients were included to assess the effect. The results showed that high levels of TRIM59 were significantly associated with poor OS in cancer patients (HR = 1.43, 95%CI: 1.24-1.66, P < .001), indicating that higher TRIM59 expression could be an independent prognostic factor for poor survival in cancer patients.
CONCLUSION
Our meta-analysis suggests that higher TRIM59 expression predicts poor prognosis in cancer patients, and it may therefore serve as a promising prognostic factor.
Topics: Biomarkers, Tumor; Humans; Intracellular Signaling Peptides and Proteins; Membrane Proteins; Metalloproteins; Neoplasms; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Survival Analysis; Tripartite Motif Proteins
PubMed: 31770215
DOI: 10.1097/MD.0000000000018024 -
Critical Reviews in Clinical Laboratory... Dec 2019Iron deficiency is the most common micronutrient deficiency in the world and represents a major challenge for public health, notably in terms of morbidity and mortality....
Iron deficiency is the most common micronutrient deficiency in the world and represents a major challenge for public health, notably in terms of morbidity and mortality. It remains largely under-diagnosed due to the low level of exploration and the absence of international harmonization for biological tests and thresholds. We performed a systematic review of the literature using PubMed, which allowed us to identify 41 publications within the scope of this review. This analysis shows the benefit of using transferrin saturation in addition to ferritin, in the diagnosis of iron deficiency and even in first-line analysis for patients with chronic inflammatory diseases.
Topics: Ferritins; Humans; Iron; Iron Deficiencies; Publications; Transferrins
PubMed: 31503510
DOI: 10.1080/10408363.2019.1653820 -
The Cochrane Database of Systematic... Mar 2020Lactoferrin, a normal component of human colostrum and milk, can enhance host defenses and may be effective for prevention of sepsis and necrotizing enterocolitis (NEC)... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Lactoferrin, a normal component of human colostrum and milk, can enhance host defenses and may be effective for prevention of sepsis and necrotizing enterocolitis (NEC) in preterm neonates.
OBJECTIVES
To assess the safety and effectiveness of lactoferrin supplementation to enteral feeds for prevention of sepsis and NEC in preterm neonates. Secondarily, we assessed the effects of lactoferrin supplementation to enteral feeds on the duration of positive-pressure ventilation, development of chronic lung disease (CLD) or periventricular leukomalacia (PVL), length of hospital stay to discharge among survivors, and adverse neurological outcomes at two years of age or later.
SEARCH METHODS
We used the standard search strategy of Cochrane Neonatal to update our search. We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2019, Issue 9), MEDLINE via PubMed (1966 to 20 January 2020), PREMEDLINE (1996 to 20 January 2020), Embase (1980 to 20 January 2020), and CINAHL (1982 to 20 January 2020). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomized controlled trials and quasi-randomized trials.
SELECTION CRITERIA
In our search, we included randomized controlled trials (RCTs) evaluating enteral lactoferrin supplementation at any dose or duration to prevent sepsis or NEC in preterm neonates.
DATA COLLECTION AND ANALYSIS
We used the standard methods of Cochrane Neonatal and the GRADE approach to assess the certainty of evidence.
MAIN RESULTS
Meta-analysis of data from twelve randomized controlled trials showed that lactoferrin supplementation to enteral feeds decreased late-onset sepsis (typical RR 0.82, 95% CI 0.74 to 0.91; typical RD -0.04, 95% CI, -0.06, -0.02; NNTB 25, 95% CI 17 to 50; 12 studies, 5425 participants, low-certainty evidence) and decreased length of hospital stay (MD -2.38, 95% CI, -4.67, -0.09; 3 studies, 1079 participants, low-certainty evidence). Sensitivity analysis including only good methodological certainty studies suggested a decrease in late-onset sepsis with enteral lactoferrin supplementation (typical RR 0.87, 95% CI, 0.78, 0.97; typical RD -0.03, 95% CI, -0.05, -0.0; 9 studies, 4702 participants, low-certainty evidence). There were no differences in NEC stage II or III (typical RR 1.10, 95% CI, 0.86, 1.41; typical RD -0.00, 95% CI, -0.02, 0.01; 7 studies, 4874 participants; low-certainty evidence) or 'all-cause mortality' (typical RR 0.90, 95% CI 0.69, 1.17; typical RD -0.00, 95% CI, -0.01, 0.01; 11 studies, 5510 participants; moderate-certainty evidence). One study reported no differences in neurodevelopmental testing by Mullen's or Bayley III at 24 months of age after enteral lactoferrin supplementation (one study, 292 participants, low-certainty evidence). Lactoferrin supplementation to enteral feeds with probiotics decreased late-onset sepsis (RR 0.25, 95% CI 0.14 to 0.46; RD -0.13, 95% CI -0.18 to -0.08; NNTB 8, 95% CI 6 to 13; 3 studies, 564 participants; low-certainty evidence) and NEC stage II or III (RR 0.04, 95% CI 0.00 to 0.62; RD -0.05, 95% CI -0.08 to -0.03; NNTB 20, 95% CI 12.5 to 33.3; 1 study, 496 participants; very low-certainty evidence), but not 'all-cause mortality' (very low-certainty evidence). Lactoferrin supplementation to enteral feeds with or without probiotics had no effect on CLD, duration of mechanical ventilation or threshold retinopathy of prematurity (low-certainty evidence). Investigators reported no adverse effects in the included studies.
AUTHORS' CONCLUSIONS
We found low-certainty evidence from studies of good methodological quality that lactoferrin supplementation of enteral feeds decreases late-onset sepsis but not NEC ≥ stage II or 'all cause mortality' or neurodevelopmental outcomes at 24 months of age in preterm infants without adverse effects. Low- to very low-certainty evidence suggests that lactoferrin supplementation of enteral feeds in combination with probiotics decreases late-onset sepsis and NEC ≥ stage II in preterm infants without adverse effects, however, there were few included studies of poor methodological quality. The presence of publication bias and small studies of poor methodology that may inflate the effect size make recommendations for clinical practice difficult.
Topics: Administration, Oral; Bacterial Infections; Cause of Death; Chronic Disease; Enteral Nutrition; Enterocolitis, Necrotizing; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Lacticaseibacillus rhamnosus; Lactoferrin; Lung Diseases; Mycoses; Numbers Needed To Treat; Probiotics; Randomized Controlled Trials as Topic; Retinopathy of Prematurity; Sepsis
PubMed: 32232984
DOI: 10.1002/14651858.CD007137.pub6