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Clinical Gastroenterology and... Aug 2018Tests to quantify fecal levels of chymotrypsin like elastase family member 3 (CELA3 or elastase-1) in feces are widely used to identify patients with exocrine pancreatic... (Meta-Analysis)
Meta-Analysis
BACKGROUND & AIMS
Tests to quantify fecal levels of chymotrypsin like elastase family member 3 (CELA3 or elastase-1) in feces are widely used to identify patients with exocrine pancreatic insufficiency (EPI). However, the diagnostic accuracy of this test, an ELISA, is not clear. We performed a systematic review and meta-analysis to determine the accuracy of measurement of fecal elastase-1 in detection of EPI.
METHODS
We searched PubMed, Embase, and reference lists for articles through November 2016 describing studies that compared fecal level of elastase-1 with results from a reference standard, direct method (secretin stimulation test), or indirect method (measurement of fecal fat) for detection of EPI. Sensitivity and specificity values were pooled statistically using bivariate diagnostic meta-analysis.
RESULTS
We included total of 428 cases of EPI and 673 individuals without EPI (controls), from 14 studies, in the meta-analysis. The assay for elastase-1, compared to secretin stimulation test, identified patients with pancreatic insufficiency with a pooled sensitivity value of 0.77 (95% CI, 0.58-0.89) and specificity value of 0.88 (95% CI, 0.78-0.93). In an analysis of 345 cases of EPI and 312 controls, from 6 studies, the fecal elastase-1 assay identified patients with EPI with a pooled sensitivity value of 0.96 (95% CI, 0.79-0.99) and specificity value of 0.88 (95% CI, 0.59-0.97), compared to quantitative fecal fat estimation. In patients with low pre-test probability of EPI (5%), the fecal elastase-1 assay would have a false-negative rate of 1.1% and a false-positive rate of 11%, indicating a high yield in ruling out EPI but not in detection of EPI. In contrast, in patients with high pre-test probability of EPI (40%), approximately 10% of patients with EPI would be missed (false negatives).
CONCLUSIONS
In a systematic review and meta-analysis of studies that compared fecal level of elastase-1 for detection of EPI, we found that normal level of elastase-1 (above 200 mcg/g) can rule out EPI in patients with a low probability of this disorder (such as those with irritable bowel syndrome with diarrhea). However, in these patients, an abnormal level of elastase-1 (below 200 mcg/g) has a high false-positive rate.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Child, Preschool; Diagnostic Tests, Routine; Exocrine Pancreatic Insufficiency; Feces; Female; Humans; Infant; Infant, Newborn; Male; Middle Aged; Pancreatic Elastase; Sensitivity and Specificity; Young Adult
PubMed: 29374614
DOI: 10.1016/j.cgh.2018.01.027 -
Journal of Cosmetic Dermatology Dec 2022The ubiquitin-proteasome system (UPS) is a highly conserved way of regulating intracellular protein balance. UPS mediates proteolysis and disruption of variation or... (Review)
Review
BACKGROUND
The ubiquitin-proteasome system (UPS) is a highly conserved way of regulating intracellular protein balance. UPS mediates proteolysis and disruption of variation or misfolding, while finely regulating proteins involved in differentiation and other biological processes.
AIMS
The aim of this review is to systematically introduce UPS as a key regulator of melanin metabolism.
METHODS
Systematic search and retrospective review were performed on the published data.
RESULTS
Melanocyte-inducing transcription factor (MITF) is a substrate of the ubiquitin ligase VCHL1 and acts as a transcription factor to regulate the expression of key enzymes in melanin synthesis such as tyrosinase (TYR). The rate-limiting enzyme TYR is modified by the ubiquitin ligase Hrd1 during melanosynthesis. Melanin itself is also regulated by multiple ubiquitin ligases including Fbp1 and Vhl. By regulating the ubiquitination modification to target each link of melanin synthesis, it plays an important role in correcting the disorder of melanin metabolism. A number of chemical agents have been proven to inhibit the activity of ubiquitin ligase.
CONCLUSIONS
Drugs targeting E3 ligase and deubiquitinating enzymes have great potential in the treatment of melanin metabolism disorders.
Topics: Humans; Melanins; Proteasome Endopeptidase Complex; Transcription Factors; Ubiquitin; Ubiquitin-Protein Ligases
PubMed: 36207998
DOI: 10.1111/jocd.15433 -
Neurobiology of Disease Jun 2024Research evidence indicating common metabolic mechanisms through which type 2 diabetes mellitus (T2DM) increases risk of late-onset Alzheimer's dementia (LOAD) has... (Meta-Analysis)
Meta-Analysis Review
Research evidence indicating common metabolic mechanisms through which type 2 diabetes mellitus (T2DM) increases risk of late-onset Alzheimer's dementia (LOAD) has accumulated over recent decades. The aim of this systematic review is to provide a comprehensive review of common mechanisms, which have hitherto been discussed in separate perspectives, and to assemble and evaluate candidate loci and epigenetic modifications contributing to polygenic risk linkages between T2DM and LOAD. For the systematic review on pathophysiological mechanisms, both human and animal studies up to December 2023 are included. For the qualitative meta-analysis of genomic bases, human association studies were examined; for epigenetic mechanisms, data from human studies and animal models were accepted. Papers describing pathophysiological studies were identified in databases, and further literature gathered from cited work. For genomic and epigenomic studies, literature mining was conducted by formalised search codes using Boolean operators in search engines, and augmented by GeneRif citations in Entrez Gene, and other sources (WikiGenes, etc.). For the systematic review of pathophysiological mechanisms, 923 publications were evaluated, and 138 gene loci extracted for testing candidate risk linkages. 3 57 publications were evaluated for genomic association and descriptions of epigenomic modifications. Overall accumulated results highlight insulin signalling, inflammation and inflammasome pathways, proteolysis, gluconeogenesis and glycolysis, glycosylation, lipoprotein metabolism and oxidation, cell cycle regulation or survival, autophagic-lysosomal pathways, and energy. Documented findings suggest interplay between brain insulin resistance, neuroinflammation, insult compensatory mechanisms, and peripheral metabolic dysregulation in T2DM and LOAD linkage. The results allow for more streamlined longitudinal studies of T2DM-LOAD risk linkages.
Topics: Humans; Diabetes Mellitus, Type 2; Alzheimer Disease; Animals; Epigenesis, Genetic
PubMed: 38643861
DOI: 10.1016/j.nbd.2024.106485 -
Meat Science Oct 2017Consumers are the final step in the meat supply chain and meeting consumer expectations of quality and tenderness are important for satisfaction and repeat purchase.... (Meta-Analysis)
Meta-Analysis Review
Consumers are the final step in the meat supply chain and meeting consumer expectations of quality and tenderness are important for satisfaction and repeat purchase. High pressure processing, shockwaves, ultrasound, pulsed electric field and muscle stretching can be applied to pre- and post-rigor meat for tenderisation. These non-thermal and thermal innovative technologies can be used with varying levels of success to cause physical disruption to muscle structure, enhanced proteolysis and ageing and muscle protein denaturation and solubilisation resulting in changes to texture and juiciness. Results of a meta-analysis are used to compare the effects of these technologies on meat tenderisation. In the future, a combination of new and innovative technologies will be ideally suited to deliver a range of desired textures for meat products.
Topics: Animals; Food Quality; Food Technology; High-Energy Shock Waves; Livestock; Meat; Muscle Proteins; Poultry; Proteolysis; Ultrasonic Waves
PubMed: 28666558
DOI: 10.1016/j.meatsci.2017.04.241 -
Critical Reviews in Food Science and... Jan 2018Legume lectins are carbohydrate-binding proteins of non-immune origin. Significant amounts of lectins have been found in Phaseolus vulgaris beans as far back as in the... (Review)
Review
Legume lectins are carbohydrate-binding proteins of non-immune origin. Significant amounts of lectins have been found in Phaseolus vulgaris beans as far back as in the last century; however, many questions about their potential biological roles still remain obscure. Studies have shown that lectins are anti-nutritional factors that can cause intestinal disorders. Owing to their ability to act as toxic allergens and hemagglutinins, the Phaseolus vulgaris lectins are of grave concern for human health and safety. Nonetheless, their potential beneficial health effects, such as anti-cancer, anti-human immunodeficiency virus (anti-HIV), anti-microbial infection, preventing mucosal atrophy, reducing type 2 diabetes and obesity, promoting nutrients absorption and targeting drugs, are of immense interest. The significance of Phaseolus vulgaris lectins in biological researches and the potential biomedical applications have placed tremendous emphasis on the development of purification strategies to obtain the protein in pure and stable forms. These purification strategies entail considerations such as effects of proteolysis, heating, gamma radiation, and high-hydrostatic-pressure that can have crucial outcomes in either eliminating or improving bioactivities of the lectins. Thus, up-to-date research findings of Phaseolus vulgaris lectins on different aspects such as anti-nutritional and health impacts, purification strategies and novel processing trends, are systematically reviewed.
Topics: Animals; Anti-HIV Agents; Anti-Infective Agents; Anticarcinogenic Agents; Diet; Digestion; Drug Stability; Female; Food Handling; Health Promotion; Humans; Immunity; Intestinal Diseases; Male; Phytohemagglutinins
PubMed: 26479307
DOI: 10.1080/10408398.2015.1096234 -
Advances in Nutrition (Bethesda, Md.) Jan 2023When there is an inadequate supply of mother's milk, pasteurized donor human milk is preferred over formula to supplement feeds for preterm infants. Although providing... (Review)
Review
When there is an inadequate supply of mother's milk, pasteurized donor human milk is preferred over formula to supplement feeds for preterm infants. Although providing donor milk helps to improve feeding tolerance and reduce necrotizing enterocolitis, changes to its composition and reductions in bioactivity during processing, are thought to contribute to the slower growth often exhibited by these infants. To improve the clinical outcomes of recipient infants by maximizing the quality of donor milk, research is currently investigating strategies to optimize all aspects of processing, including pooling, pasteurization, and freezing; however, reviews of this literature typically only summarize the impact of a processing technique on composition or bioactivity. Reviews of published research investigating the impact of donor milk processing on infant digestion/absorption are lacking and thus, was the objective for this systematic scoping review, Open Science Framework (https://doi.org/10.17605/OSF.IO/PJTMW). Databases were searched for primary research studies evaluating donor milk processing for pathogen inactivation or other rationale and subsequent effect on infant digestion/absorption. Non-human milk studies or those assessing other outcomes were excluded. Overall, 24 articles from 12,985 records screened were included. Most studied thermal methods to inactivate pathogens, predominantly Holder pasteurization (HoP) (62.5°C, 30 min) and high-temperature short-time. Heating consistently decreased lipolysis and increased proteolysis of lactoferrin and caseins; however, protein hydrolysis was unaffected from in vitro studies. The abundance and diversity of released peptides remain unclear and should be further explored. Greater investigation into less-harsh methods for pasteurization, such as high-pressure processing, is warranted. Only 1 study assessed the impact of this technique and found minimal impact on digestion outcomes compared with HoP. Fat homogenization appeared to positively impact fat digestion (n = 3 studies), and only 1 eligible study investigated freeze-thawing. Identified knowledge gaps regarding optimal methods of processing should be further explored to improve the quality and nutrition of donor milk.
Topics: Infant, Newborn; Infant; Humans; Infant, Premature; Infant Nutritional Physiological Phenomena; Milk, Human; Nutritional Status; Digestion
PubMed: 36811588
DOI: 10.1016/j.advnut.2022.11.004 -
Emerging protein degradation strategies: expanding the scope to extracellular and membrane proteins.Theranostics 2021Classic small molecule inhibitors that directly target pathogenic proteins typically rely on the accessible binding sites to achieve prolonged occupancy and influence... (Review)
Review
Classic small molecule inhibitors that directly target pathogenic proteins typically rely on the accessible binding sites to achieve prolonged occupancy and influence protein functions. The emerging targeted protein degradation (TPD) strategies exemplified by PROteolysis TArgeting Chimeras (PROTACs) are revolutionizing conventional drug discovery modality to target proteins of interest (POIs) that were categorized as "undruggable" before, however, these strategies are limited within intracellular POIs. The novel new degrader technologies such as LYsosome-TArgeting Chimaeras (LYTACs) and Antibody-based PROTACs (AbTACs) have been successfully developed to expand the scope of TPD to extracellular and membrane proteins, fulfilling huge unmet medical needs. Here, we systematically review the currently viable protein degradation strategies, emphasize that LYTACs and AbTACs turn a new avenue for the development of TPD, and highlight the potential challenges and directions in this vibrant field.
Topics: Animals; Cellular Microenvironment; Drug Delivery Systems; Drug Discovery; Humans; Lysosomes; Membrane Proteins; Proteasome Endopeptidase Complex; Proteins; Proteolysis
PubMed: 34373745
DOI: 10.7150/thno.62686 -
International Journal of Molecular... Oct 2022The plant-microbe holobiont has garnered considerable attention in recent years, highlighting its importance as an ecological unit. Similarly, manipulation of the... (Review)
Review
An Insight into Microbial Inoculants for Bioconversion of Waste Biomass into Sustainable "Bio-Organic" Fertilizers: A Bibliometric Analysis and Systematic Literature Review.
The plant-microbe holobiont has garnered considerable attention in recent years, highlighting its importance as an ecological unit. Similarly, manipulation of the microbial entities involved in the rhizospheric microbiome for sustainable agriculture has also been in the limelight, generating several commercial bioformulations to enhance crop yield and pest resistance. These bioformulations were termed biofertilizers, with the consistent existence and evolution of different types. However, an emerging area of interest has recently focused on the application of these microorganisms for waste valorization and the production of "bio-organic" fertilizers as a result. In this study, we performed a bibliometric analysis and systematic review of the literature retrieved from Scopus and Web of Science to determine the type of microbial inoculants used for the bioconversion of waste into "bio-organic" fertilizers. The , species, cyanobacterial biomass species, sp. and sp. were identified to be consistently used for the recovery of nutrients and bioconversion of wastes used for the promotion of plant growth. Cyanobacterial strains were used predominantly for wastewater treatment, while and were used on a wide variety of wastes such as sawdust, agricultural waste, poultry bone meal, crustacean shell waste, food waste, and wastewater treatment plant (WWTP) sewage sludge ash. Several bioconversion strategies were observed such as submerged fermentation, solid-state fermentation, aerobic composting, granulation with microbiological activation, and biodegradation. Diverse groups of microorganisms (bacteria and fungi) with different enzymatic functionalities such as chitinolysis, lignocellulolytic, and proteolysis, in addition to their plant growth promoting properties being explored as a consortium for application as an inoculum waste bioconversion to fertilizers. Combining the efficiency of such functional and compatible microbial species for efficient bioconversion as well as higher plant growth and crop yield is an enticing opportunity for "bio-organic" fertilizer research.
Topics: Fertilizers; Biomass; Agricultural Inoculants; Food; Refuse Disposal; Sewage; Bibliometrics; Soil
PubMed: 36361844
DOI: 10.3390/ijms232113049 -
European Journal of Medicinal Chemistry Dec 2023Proteolysis-targeting chimeras (PROTACs) have been an area of intensive research with the potential to extend drug space not target to traditional molecules. In the last... (Review)
Review
Proteolysis-targeting chimeras (PROTACs) have been an area of intensive research with the potential to extend drug space not target to traditional molecules. In the last half decade, we have witnessed several PROTACs initiated phase I/II/III clinical trials, which inspired us a lot. However, the structure of PROTACs beyond "rule of 5" resulted in developing PROTACs with acceptable oral pharmacokinetic (PK) properties remain one of the biggest bottleneck tasks. Many reports have demonstrated that it is possible to access orally bioavailable PROTACs through rational ligand and linker modifications. In this review, we systematically reviewed and highlighted the most recent advances in orally bioavailable PROTACs development, especially focused on the medicinal chemistry campaign of discovery process and in vivo oral PK properties. Moreover, the constructive strategies for developing oral PROTACs were proposed comprehensively. Collectively, we believe that the strategies summarized here may provide references for further development of oral PROTACs.
Topics: Proteolysis Targeting Chimera; Chemistry, Pharmaceutical; Proteolysis; Ubiquitin-Protein Ligases
PubMed: 37708797
DOI: 10.1016/j.ejmech.2023.115793 -
Urologic Oncology May 2022Determining meta-analysis of transcriptional profiling of muscle-invasive bladder cancer (MIBC) through Gene Expression Omnibus (GEO) datasets has not been investigated.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Determining meta-analysis of transcriptional profiling of muscle-invasive bladder cancer (MIBC) through Gene Expression Omnibus (GEO) datasets has not been investigated. This study aims to define gene expression profiles in MIBC and to identify potential candidate genes and pathways.
OBJECTIVES
To review and evaluate gene expression studies in MIBC through publicly available RNA sequencing (RNA-Seq) and microarray data in order to identify potential prognostic and therapeutic targets for MIBC.
METHODS
A systematic literature search of the Ovid MEDLINE, PubMed, and Wiley Cochrane Central Register of Controlled Trials databases was performed using the terms "gene," "gene expression," and "bladder cancer" January 1, 1990 through March 2021 focused on populations with MIBC.
RESULTS
In the final analysis, GEO datasets were included. Fixed effect model was employed in the meta-analysis. Gene networking connections and gene-set functional analyses of the identified genes as differentially expressed in MIBC were performed using ImaGEO and GeneMANIA software. A heatmap for the upregulated and downregulated genes was generated along with the correlated pathways.
CONCLUSION
A total of 9 genes were reported in this analysis. Six genes were reported as upregulated (ProTα, SPINT1, UBE2E1, RAB25, KPNB1, HDAC1) and 3 genes as downregulated (NUP188, IPO13, NUP124). Genes were found to be involved in "ubiquitin mediated proteolysis," "protein processing in endoplasmic reticulum," "transcriptional misregulation in cancer," and "RNA transport" pathways.
Topics: Female; Gene Expression Profiling; Gene Regulatory Networks; Humans; Male; Muscles; Neoplasm Invasiveness; Prognosis; Urinary Bladder Neoplasms; rab GTP-Binding Proteins
PubMed: 35039218
DOI: 10.1016/j.urolonc.2021.11.003