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Amino Acids Sep 2018Advanced glycation end products (AGEs) are a cluster of heterogeneous molecules that are generated in a non-enzymatic reaction by the binding of sugars with amino groups... (Review)
Review
Advanced glycation end products (AGEs) are a cluster of heterogeneous molecules that are generated in a non-enzymatic reaction by the binding of sugars with amino groups of DNA, lipids and proteins. Carnosine is a naturally occurring dipeptide with antioxidant activity, which inhibits protein carbonylation and glycoxidation. This systematic review searched international sources for all published and unpublished original research in English from any year up to the end of April 2018. An electronic search of PubMed, Scopus and Google Scholar was conducted. 187 articles were initially found and 133 articles were selected after excluding duplicated data. Review articles, studies based on the components of carnosine and studies that were about the effects of carnosine on AGEs-induced changes were excluded. In total, 36 studies met the inclusion criteria. This included 19 in vitro studies, 15 animal studies and two human studies. All but two of the studies indicated that carnosine can prevent the formation of AGEs. The findings of this review indicating that carnosine has anti-glycating properties, and may hinder the formation of protein carbonyls and the cross-links induced by reduced sugars; however, there were few human studies. The mechanism by which carnosine prevents the formation of AGEs needs further investigation.
Topics: Animals; Carnosine; Glycation End Products, Advanced; Humans; Protein Carbonylation; Proteins
PubMed: 29858687
DOI: 10.1007/s00726-018-2592-9 -
European Journal of Gastroenterology &... Dec 2015Estrogen receptor β (ERβ) is a potential tumor-suppressor gene in colorectal cancer (CRC). This hypothesis is supported by clinical and laboratory observations. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Estrogen receptor β (ERβ) is a potential tumor-suppressor gene in colorectal cancer (CRC). This hypothesis is supported by clinical and laboratory observations.
AIM
In this meta-analysis, we looked at studies that investigated the relationship between ERβ protein expression and CRC, comparing the lesion with normal adjacent mucosa.
METHODS
English medical literature searches were performed for ERβ expression in patients with CRC, tumor tissue versus normal mucosa. Searches were performed up to 31 May 2015, using MEDLINE, PubMed, EMBASE, Scopus, and CENTRAL. Meta-analysis was carried out using Comprehensive Meta-analysis Software. Pooled odds ratios and 95% confidence intervals were calculated and ERβ expression was compared in individual studies using the fixed-effects model.
RESULTS
The odds ratio of ERβ expression was 0.216 (95% confidence interval 0.152-0.307, P<0.0001), lower in cancer tissue than normal mucosa. Funnel plot did not indicate a significant publication bias. There was no significant heterogeneity in the studies included: Q=5.897, d.f.(Q)=9, I=0.000, P=0.750.
CONCLUSION
In this meta-analysis, we confirm the observation of decreased ERβ expression in CRC. Our results support the hypothesis of ERβ being a tumor-suppressor gene in the large bowel, and the ERβ protein protects against carcinogenesis and development of CRC when activated by estrogen. Further studies are needed to examine the potential of selective/specific ligands to activate ERβ without the side effects found with estrogen and without activating ERα.
SUMMARY
In this meta-analysis, we looked at studies that investigated the relationship between CRC and ERβ expression in the tumor and normal mucosa of CRC patients. English medical literature searches were performed for studies comparing ERβ expression in the cancer and normal colonic mucosa in patients with CRC. Meta-analysis was carried out, pooled odds ratios were calculated, and ERβ expression was compared in individual studies.
Topics: Colon; Colorectal Neoplasms; Estrogen Receptor beta; Gene Expression Regulation, Neoplastic; Humans; Intestinal Mucosa; Neoplasm Proteins
PubMed: 26367493
DOI: 10.1097/MEG.0000000000000471 -
Sports Medicine and Arthroscopy Review Sep 2016Mounting research in the field of sports concussion biomarkers has led to a greater understanding of the effects of brain injury from sports. A recent systematic review... (Review)
Review
Mounting research in the field of sports concussion biomarkers has led to a greater understanding of the effects of brain injury from sports. A recent systematic review of clinical studies examining biomarkers of brain injury following sports-related concussion established that almost all studies have been published either in or after the year 2000. In an effort to prevent chronic traumatic encephalopathy and long-term consequences of concussion, early diagnostic and prognostic tools are becoming increasingly important; particularly in sports and in military personnel, where concussions are common occurrences. Early and tailored management of athletes following a concussion with biomarkers could provide them with the best opportunity to avoid further injury. Should blood-based biomarkers for concussion be validated and become widely available, they could have many roles. For instance, a point-of-care test could be used on the field by trained sport medicine professionals to help detect a concussion. In the clinic or hospital setting, it could be used by clinicians to determine the severity of concussion and be used to screen players for neuroimaging (computed tomography and/or magnetic resonance imaging) and further neuropsychological testing. Furthermore, biomarkers could have a role in monitoring progression of injury and recovery and in managing patients at high risk of repeated injury by being incorporated into guidelines for return to duty, work, or sports activities. There may even be a role for biomarkers as surrogate measures of efficacy in the assessment of new treatments and therapies for concussion.
Topics: Biomarkers; Brain Concussion; Glial Fibrillary Acidic Protein; Humans; Magnetic Resonance Imaging; Neurofilament Proteins; Phosphopyruvate Hydratase; S100 Calcium Binding Protein beta Subunit; Tomography, X-Ray Computed; Ubiquitin Thiolesterase; tau Proteins
PubMed: 27482776
DOI: 10.1097/JSA.0000000000000117 -
Physiological Reports Aug 2023Dietary protein ingestion augments post (resistance) exercise muscle protein synthesis (MPS) rates. It is thought that the dose of leucine ingested within the protein... (Review)
Review
BACKGROUND
Dietary protein ingestion augments post (resistance) exercise muscle protein synthesis (MPS) rates. It is thought that the dose of leucine ingested within the protein (leucine threshold hypothesis) and the subsequent plasma leucine variables (leucine trigger hypothesis; peak magnitude, rate of rise, and total availability) determine the magnitude of the postprandial postexercise MPS response.
METHODS
A quantitative systematic review was performed extracting data from studies that recruited healthy adults, applied a bout of resistance exercise, ingested a bolus of protein within an hour of exercise, and measured plasma leucine concentrations and MPS rates (delta change from basal).
RESULTS
Ingested leucine dose was associated with the magnitude of the MPS response in older, but not younger, adults over acute (0-2 h, r = 0.64, p = 0.02) and the entire postprandial (>2 h, r = 0.18, p = 0.01) period. However, no single plasma leucine variable possessed substantial predictive capacity over the magnitude of MPS rates in younger or older adults.
CONCLUSION
Our data provide support that leucine dose provides predictive capacity over postprandial postexercise MPS responses in older adults. However, no threshold in older adults and no plasma leucine variable was correlated with the magnitude of the postexercise anabolic response.
Topics: Humans; Aged; Leucine; Muscle Proteins; Diet; Muscle, Skeletal; Dietary Proteins; Postprandial Period
PubMed: 37537134
DOI: 10.14814/phy2.15775 -
International Orthopaedics Jun 2016Because of significant complications related to the use of autologous bone grafts in spinal fusion surgery, bone substitutes and growth factors such as bone... (Review)
Review
PURPOSE
Because of significant complications related to the use of autologous bone grafts in spinal fusion surgery, bone substitutes and growth factors such as bone morphogenetic protein (BMP) have been developed. One of them, recombinant human (rh) BMP-2, has been approved by the Food and Drug Administration (FDA) for use under precise conditions. However, rhBMP-2-related side effects have been reported, used in FDA-approved procedures, but also in off-label use.A systematic review of clinical data was conducted to analyse the rhBMP-2-related adverse events (AEs), in order to assess their prevalence and the associated surgery practices.
METHODS
Medline search with keywords "bone morphogenetic protein 2", "lumbar spine", "anterolateral interbody fusion" (ALIF) and the filter "clinical trial". FDA published reports were also included. Study assessment was made by authors (experienced spine surgeons), based on quality of study designs and level of evidence.
RESULTS
Extensive review of randomised controlled trials (RCTs) and controlled series published up to the present point, reveal no evidence of a significant increase of AEs related to rhBMP-2 use during ALIF surgeries, provided that it is used following FDA guidelines. Two additional RCTs performed with rhBMP-2 in combination with allogenic bone dowels reported increased bone remodelling in BMP-treated patients. This AE was transient and had no consequence on the clinical outcome of the patients. No other BMP-related AEs were reported in these studies.
CONCLUSIONS
This literature review confirms that the use of rhBMP-2 following FDA-approved recommendations (i.e. one-level ALIF surgery with an LT-cage) is safe. The rate of complications is low and the AEs had been identified by the FDA during the pre-marketing clinical trials. The clinical efficiency of rhBMP-2 is equal or superior to that of allogenic or autologous bone graft in respect to fusion rate, low back pain disability, patient satisfaction and rate of re-operations. For all other off-label use, the safety and effectiveness of rhBMP-2 have not been established, and further RCTs with high level of evidence are required.
Topics: Adult; Bone Morphogenetic Protein 2; Bone Transplantation; Female; Humans; Low Back Pain; Lumbar Vertebrae; Male; Middle Aged; Off-Label Use; Postoperative Complications; Recombinant Proteins; Spinal Fusion; Transforming Growth Factor beta
PubMed: 26961193
DOI: 10.1007/s00264-016-3149-8 -
Journal of Pediatric Gastroenterology... Dec 2017The aim of the study was to systematically review the diagnostic utility of serum biomarkers for the diagnosis of necrotizing enterocolitis (NEC). (Review)
Review
OBJECTIVE
The aim of the study was to systematically review the diagnostic utility of serum biomarkers for the diagnosis of necrotizing enterocolitis (NEC).
METHODS
We conducted an electronic and manual search of the available evidence. We included studies reporting data on the diagnostic accuracy of "serum" biomarkers for the diagnosis of NEC, available until January 2016.
RESULTS
We selected 22 studies from the 1296 articles retrieved. Only S100 A8/A9 protein and apolipoprotein-CII showed high sensitivity (100% and 96.4%, respectively) and specificity (90% and 95%, respectively) in the studies using Bell stage II NEC as target condition. High sensitivity and specificity were reported for interleukin-10 (100% and 90%), interleukin1-receptor antagonist (100% and 91.7%), intestinal fatty acid-binding protein (100% and 91%) and ischemia-modified albumin (94.7% and 92%), when tested to predict the evolution from definite to advanced NEC. Given the amount of uncertainty, the limited availability of data and heterogeneity among the populations in the different studies, we were unable to perform a meta-analysis. Major concerns about the applicability stemmed from the spectrum of patients enrolled and the inclusion of diseases different from Bell stage ≥2 NEC as target conditions.
CONCLUSIONS
We identified only few markers with good diagnostic accuracy and found an overall low quality of the studies on serum NEC biomarkers. In conclusion, data supporting their use are insufficient.
Topics: Apolipoprotein C-II; Biomarkers; Calgranulin A; Disease Progression; Enterocolitis, Necrotizing; Fatty Acid-Binding Proteins; Humans; Interleukin-10; Sensitivity and Specificity; Serum Albumin, Human
PubMed: 28379923
DOI: 10.1097/MPG.0000000000001588 -
Nestle Nutrition Institute Workshop... 2016Presently, hydrolyzed formulas (HF) are used primarily in infants that cannot be exclusively breastfed, those with cow's milk allergy and for primary prevention of... (Review)
Review
Presently, hydrolyzed formulas (HF) are used primarily in infants that cannot be exclusively breastfed, those with cow's milk allergy and for primary prevention of allergic disease, but HFs are increasingly being used worldwide, begging the question if they may be recommended as the optimal choice for all standard-risk, full-term, non-exclusively breastfed infants. Data regarding the nutritional adequacy of modern-day HFs are scarce and lack long-term data suggesting that growth in infants fed HF versus an intact protein formula (IPF) is different. While human breast milk is the optimal source of nutrition for multiple reasons, a 2006 systematic review determined there were no comparable long-term studies regarding prolonged use of HFs versus breastfeeding. Meta-analyses of formula consumption and risk of atopic dermatitis (AD) have found that infants fed partially HF compared to IPF had a lower risk of AD, but there are significant limitations to these studies, making conclusions about the general use of HFs problematic. Costs should be considered in decision-making regarding the choice of the formula, but global comparison of this is difficult given large cost differences in different countries. Despite the issues raised here, the desire to provide concrete recommendations of widespread HF use needs to be balanced carefully in order not to overstate claims of benefit. Long-term studies are needed to investigate the feasibility of HF as a routine feeding option for healthy, standard-risk infants. Because of the paucity of data, routine use of HF as an equivalent option to breastfeeding or IPF cannot be supported at present based on available scientific evidence.
Topics: Animals; Breast Feeding; Cattle; Child Development; Cost-Benefit Analysis; Dermatitis, Atopic; Humans; Infant; Infant Formula; Infant Nutritional Physiological Phenomena; Meta-Analysis as Topic; Milk Hypersensitivity; Milk Proteins; Protein Hydrolysates; Randomized Controlled Trials as Topic; Risk Factors
PubMed: 27336594
DOI: 10.1159/000442956 -
The Lancet. Psychiatry Apr 2023Immune system dysfunction is considered to play an aetiological role in schizophrenia spectrum disorders, with substantial alterations in the concentrations of specific... (Meta-Analysis)
Meta-Analysis
Alteration patterns of peripheral concentrations of cytokines and associated inflammatory proteins in acute and chronic stages of schizophrenia: a systematic review and network meta-analysis.
BACKGROUND
Immune system dysfunction is considered to play an aetiological role in schizophrenia spectrum disorders, with substantial alterations in the concentrations of specific peripheral inflammatory proteins, such as cytokines. However, there are inconsistencies in the literature over which inflammatory proteins are altered throughout the course of illness. Through conducting a systematic review and network meta-analysis, this study aimed to investigate the patterns of alteration that peripheral inflammatory proteins undergo in both acute and chronic stages of schizophrenia spectrum disorders, relative to a healthy control population.
METHODS
In this systematic review and meta-analysis, we searched PubMed, PsycINFO, EMBASE, CINAHL, and the Cochrane Central Register of Controlled Trials from inception to March 31, 2022, for published studies reporting peripheral inflammatory protein concentrations in cases of people with schizophrenia-spectrum disorders and healthy controls. Inclusion criteria were: (1) observational or experimental design; (2) a population consisting of adults diagnosed with schizophrenia-spectrum disorders with a specified indicator of acute or chronic stage of illness; (3) a comparable healthy control population without mental illness; (4) a study outcome measuring the peripheral protein concentration of a cytokine, associated inflammatory marker, or C-reactive protein. We excluded studies that did not measure cytokine proteins or associated biomarkers in blood. Mean and SDs of inflammatory marker concentrations were extracted directly from full-text publshed articles; articles that did not report data as results or supplementary results were excluded (ie, authors were not contacted) and grey literature and unpublished studies were not sought. Pairwise and network meta-analyses were done to measure the standardised mean difference in peripheral protein concentrations between three groups: individuals with acute schizophrenia-spectrum disorder, individuals with chronic schizophrenia-spectrum disorder, and healthy controls. This protocol was registered on PROSPERO, CRD42022320305.
FINDINGS
Of 13 617 records identified in the database searches, 4492 duplicates were removed, 9125 were screened for eligibility, 8560 were excluded after title and abstract screening, and three were excluded due to limited access to the full-text article. 324 full-text articles were then excluded due to inappropriate outcomes, mixed or undefined schizophrenia cohorts, or duplicate study populations, five were removed due to concerns over data integrity, and 215 studies were included in the meta-analysis. 24 921 participants were included, with 13 952 adult cases of schizophrenia-spectrum disorder and 10 969 adult healthy controls (descriptive data for the entire cohort were not available for age, numbers of males and females, and ethnicity). Concentration of interleukin (IL)-1β, IL-1 receptor antagonist (IL-1RA), soluble interleukin-2 receptor (sIL-2R), IL-6, IL-8, IL-10, tumour necrosis factor (TNF)-α, and C-reactive protein were consistently elevated in both individuals with acute schizophrenia-spectrum disorder and chronic schizophrenia-spectrum disorder, relative to healthy controls. IL-2 and interferon (IFN)-γ were significantly elevated in acute schizophrenia-spectrum disorder, while IL-4, IL-12, and IFN-γ were significantly decreased in chronic schizophrenia-spectrum disorder. Sensitivity and meta-regression analyses revealed that study quality and a majority of the evaluated methodological, demographic, and diagnostic factors had no significant impact on the observed results for most of the inflammatory markers. Specific exceptions to this included: methodological factors of assay source (for IL-2 and IL-8), assay validity (for IL-1β), and study quality (for transforming growth factor-β1); demographic factors of age (for IFN-γ, IL-4, and IL-12), sex (for IFN-γ and IL-12), smoking (for IL-4), and BMI (for IL-4); and diagnostic factors including diagnostic composition of schizophrenia-spectrum cohort (for IL-1β IL-2, IL-6, and TNF-α), antipsychotic-free cases (for IL-4 and IL-1RA), illness duration (for IL-4), symptom severity (for IL-4), and subgroup composition (for IL-4).
INTERPRETATION
Results suggest that people with schizophrenia-spectrum disorders have a baseline level of inflammatory protein alteration throughout the illness, as reflected by consistently elevated pro-inflammatory proteins, hypothesised here as trait markers (eg, IL-6), while those with acute psychotic illness might have superimposed immune activity with increased concentrations of hypothesised state markers (eg, IFN-γ). Further research is required to determine whether these peripheral alterations are reflected within the central nervous system. This research facilitates an entry point in understanding how clinically relevant inflammatory biomarkers might one day be useful to the diagnosis and prognostication of schizophrenia-spectrum disorders.
FUNDING
None.
Topics: Male; Adult; Female; Humans; Cytokines; Schizophrenia; Interleukin 1 Receptor Antagonist Protein; Network Meta-Analysis; Interleukin-6; C-Reactive Protein; Interleukin-2; Interleukin-4; Interleukin-8; Tumor Necrosis Factor-alpha; Interleukin-12; Biomarkers
PubMed: 36863384
DOI: 10.1016/S2215-0366(23)00025-1 -
Spine Jul 2015Systematic review. (Review)
Review
STUDY DESIGN
Systematic review.
OBJECTIVE
To evaluate literature comparing fusion rates in anterior lumbar interbody fusion (ALIF), posterior lumbar interbody/transforaminal lumbar interbody fusion (PLIF/TLIF), and posterolateral lumbar fusion (PLF) with and without recombinant human bone morphogenetic protein-2 (rhBMP-2).
SUMMARY OF BACKGROUND DATA
rhBMP-2 is used for the FDA-approved indication of single-level ALIF with LT-Cage and off-label for PLIF/TLIF, and PLF. Due to recent controversies, it is essential to evaluate the literature for its effects on fusion rates to evaluate whether benefits outweigh potential complications.
METHODS
A Medline search was performed of clinical studies published between May 2000 and May 2012 comparing fusion rates after ALIF, PLIF/TLIF, and PLF surgery with versus without rhBMP-2. Only studies with a control arm were reviewed.
RESULTS
16 studies were reviewed (1794 patients, 995 treated with rhBMP-2 and 799 without). 5 of 5 studies for PLIF/TLIF (including 301 of 301 patients), 1 of 4 for ALIF (including 279 of 589 patients), and 3 of 7 for PLF (including 272 of 904 patients) reported no significant improvement in fusion rates with rhBMP-2 compared with those without rhBMP-2 at longest follow-up investigated. Average fusion rate 24 months after surgery was 97.8% for ALIF (n = 316), 95.7% for PLIF/TLIF (n = 141), and 93.6% for PLF (n = 422) with rhBMP-2 and 88.2% (n = 228), 89.5% (n = 86), and 83.1% (n = 372) without rhBMP-2, for ALIF, PLIF/TLIF, and PLF, respectively. Odds ratio of fusion were calculated as 7.08 (95% CI: 1.54-32.7) in ALIF, 1.98 (95% CI: 0.39-10.1) in PLIF/TLIF, and 3.06 (95% CI: 1.61-5.80) in PLF with rhBMP-2 as compared with without rhBMP-2.
CONCLUSION
Although numerous studies did not show statistically significant improvement in fusion rates with rhBMP-2 use, analysis of combined studies revealed significant improvement in fusion rate with rhBMP-2 in ALIF and PLF patients. Notably, even when pooling data from several studies, rhBMP-2 did not result in statistically significantly improved fusion rates in PLIF/TLIF. However, heterogeneity of rhBMP-2 dosing, surgical techniques, and quality of papers reviewed may limit the validity of conclusions drawn.
LEVEL OF EVIDENCE
4.
Topics: Bone Morphogenetic Protein 2; Humans; Lumbosacral Region; Recombinant Proteins; Spinal Fusion; Transforming Growth Factor beta
PubMed: 25955186
DOI: 10.1097/BRS.0000000000000971 -
Journal of Oral and Maxillofacial... May 2016Recombinant human bone morphogenetic protein-2 (rhBMP-2) is approved by the Food and Drug Administration as a viable alternative to bone graft in spinal fusion and... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Recombinant human bone morphogenetic protein-2 (rhBMP-2) is approved by the Food and Drug Administration as a viable alternative to bone graft in spinal fusion and maxillary sinus lift. The research questions for meta-analysis were: Is rhBMP-2 an effective bone graft substitute in localized alveolar ridge augmentation and maxillary sinus floor augmentation? What are the potential adverse events?
MATERIALS AND METHODS
A search of MEDLINE from January 1980 to January 2014 using PubMed, the Cochrane Database of Systematic Reviews and Controlled Trials, CINAHL, and EMBASE was performed. Searches were performed from Medical Subject Headings. The quality of each study included was graded by Review Manager software. The primary outcome variable was bone formation measured as change in bone height on computed tomogram. A systematic review of adverse events also was performed. A random-effects model was chosen. Continuous variables were calculated using the standardized mean difference and 95% confidence intervals (CIs) comparing improvement from baseline of the experimental group with that of the control group. Change in bone height was calculated using logarithmic odds ratio. Test of significance used the Z statistic with a P value of .05.
RESULTS
Ten studies met the criteria for systematic review; 8 studies were included in the meta-analysis. Five studies assessed localized alveolar ridge augmentation and resulted in an overall standardized mean difference of 0.56 (CI, 0.20-0.92) in favor of BMP; this result was statistically important. Three studies assessed maxillary sinus floor augmentation and resulted in an overall standardized mean difference of -0.50 (CI, -0.93 to -0.09), which was meaningfully different in favor of the control group. Adverse events were inconsistently reported, ranging from no complications to widespread adverse events.
CONCLUSION
For localized alveolar ridge augmentation, this meta-analysis showed that rhBMP-2 substantially increases bone height. However, rhBMP-2 does not perform as well as the autograft or allograft in maxillary sinus floor augmentation. Long-term clinical success and adverse events need to be reported with more consistency before definitive conclusions can be made.
Topics: Alveolar Ridge Augmentation; Bone Morphogenetic Protein 2; Humans; Recombinant Proteins; Sinus Floor Augmentation; Transforming Growth Factor beta
PubMed: 26707429
DOI: 10.1016/j.joms.2015.11.027