-
Computers in Biology and Medicine Mar 2023New drug discovery is inseparable from the discovery of drug targets, and the vast majority of the known targets are proteins. At the same time, proteins are essential... (Review)
Review
New drug discovery is inseparable from the discovery of drug targets, and the vast majority of the known targets are proteins. At the same time, proteins are essential structural and functional elements of living cells necessary for the maintenance of all forms of life. Therefore, protein functions have become the focus of many pharmacological and biological studies. Traditional experimental techniques are no longer adequate for rapidly growing annotation of protein sequences, and approaches to protein function prediction using computational methods have emerged and flourished. A significant trend has been to use machine learning to achieve this goal. In this review, approaches to protein function prediction based on the sequence, structure, protein-protein interaction (PPI) networks, and fusion of multi-information sources are discussed. The current status of research on protein function prediction using machine learning is considered, and existing challenges and prominent breakthroughs are discussed to provide ideas and methods for future studies.
Topics: Machine Learning; Proteins; Protein Interaction Maps
PubMed: 36680931
DOI: 10.1016/j.compbiomed.2022.106446 -
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 -
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 -
Archives of Oral Biology Dec 2019To present a genetic and protein interaction analysis associated with dental caries.
OBJECTIVE
To present a genetic and protein interaction analysis associated with dental caries.
MATERIAL AND METHODS
The first step was to conduct a systematic literature review (SLR) through an electronic database search. Case-controls that reported associations between genes and dental caries were the main type of study design used as inclusion criteria, retrieved from the PubMed and the Virtual Health Library databases, comprising the chronological range from 1982 to 2017. The SLR was guided by PRISMA protocol and the methodological quality of the studies was established through Newcastle-Ottawa Scale (NOS). In the second step, the String Protein Interaction (SPI) approach was used to analyze protein interaction (by esyN software) and also the Ingenuity Pathway Analysis (IPA) to check biological pathways associated with dental caries genes.
RESULTS
A total of 51 articles were included to perform this SLR, describing a number of 27 genes associated with dental caries development. At the genetic level, 23 genes have at least one other gene with which they interact. The genes TUFT1, VDR, TFIP11, LTF, HLA-DRB1, MMP2, MMP3 and MUC5B were shown to be connected in interactive networks by at least 10 other genes.
CONCLUSION
It is essential to apprehend the multifactorial pattern of inheritance in human disease. This study presents pathways which may be directly correlated with several dental caries phenotype and this contributes to a better understanding of this disease, opening up a wider range of biotechnology options for its effective control in the future.
Topics: Case-Control Studies; Dental Caries; Genetic Predisposition to Disease; Humans; Phenotype; Proteins
PubMed: 31476523
DOI: 10.1016/j.archoralbio.2019.104522 -
Diabetes & Metabolic Syndrome Jan 2022Due to inconsistent data about WP supplementation on inflammatory markers, present systematic review and meta-analysis was done to summarize its effect on TNF-α and IL-6. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND AIMS
Due to inconsistent data about WP supplementation on inflammatory markers, present systematic review and meta-analysis was done to summarize its effect on TNF-α and IL-6.
METHODS
Our search was done in Pubmed, Scopus, Embase, and Cochrane up to June 2021. Weighted mean difference (WMD) and 95% confidence intervals (CI) was used to indicate the effect sizes. Conceivable sources of heterogeneity were detected by subgroup analysis.
RESULTS
Overall, 11 eligible RCTs were included. The pooled results showed that WP supplementation had no significant effect on TNF-α and IL-6 status compare to those receiving carbohydrate and other types of proteins as placebo. Results from subgroup analysis based on health status, study duration, WP dosage and sex, expressed no favorable effect of WP on TNF-α and IL-6 levels.
CONCLUSION
It can be concluded that whey supplementation had no favorable effects on inflammatory biomarkers including TNF- α and IL-6.
Topics: Biomarkers; Dietary Supplements; Humans; Inflammation; Interleukin-6; Randomized Controlled Trials as Topic; Tumor Necrosis Factor-alpha; Whey; Whey Proteins
PubMed: 34998259
DOI: 10.1016/j.dsx.2021.102372 -
Molecular Pain 2021Trigeminal neuralgia (TN) is a severe facial pain disease of unknown cause and unclear genetic background. To examine the existing knowledge about genetics in TN, we...
Trigeminal neuralgia (TN) is a severe facial pain disease of unknown cause and unclear genetic background. To examine the existing knowledge about genetics in TN, we performed a systematic study asking about the prevalence of familial trigeminal neuralgia, and which genes that have been identified in human TN studies and in animal models of trigeminal pain. MedLine, Embase, Cochrane Library and Web of Science were searched from inception to January 2021. 71 studies were included in the systematic review. Currently, few studies provide information about the prevalence of familial TN; the available evidence indicates that about 1-2% of TN cases have the familial form. The available human studies propose the following genes to be possible contributors to development of TN: CACNA1A, CACNA1H, CACNA1F, KCNK1, TRAK1, SCN9A, SCN8A, SCN3A, SCN10A, SCN5A, NTRK1, GABRG1, MPZ gene, MAOA gene and SLC6A4. Their role in familial TN still needs to be addressed. The experimental animal studies suggest an emerging role of genetics in trigeminal pain, though the animal models may be more relevant for trigeminal neuropathic pain than TN per se. In summary, this systematic review suggests a more important role of genetic factors in TN pathogenesis than previously assumed.
Topics: Animals; Facial Pain; Humans; NAV1.7 Voltage-Gated Sodium Channel; Serotonin Plasma Membrane Transport Proteins; Trigeminal Neuralgia
PubMed: 34000891
DOI: 10.1177/17448069211016139 -
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 -
Current Osteoporosis Reports Oct 2019Bone turnover is a regulated process. Osteoglycin is suggested to have an important impact on bone function but may also affect cardiovascular and metabolic functions....
PURPOSE OF REVIEW
Bone turnover is a regulated process. Osteoglycin is suggested to have an important impact on bone function but may also affect cardiovascular and metabolic functions. This review investigates the action of osteoglycin in bone as well as its potential endocrine effects.
RECENT FINDINGS
Osteoglycin is expressed by several tissues including bone and muscle. Some studies suggest that osteoglycin increases osteoblast differentiation whereas others suggest that osteoglycin decreases osteoblast differentiation. Thus, findings on the influence of osteoglycin in bone are conflicting. A recent study found increased bone mass in osteoglycin deficient mice. Another study reported that osteoglycin is a marker of low bone mineral density and vertebral fractures in women with type 2 diabetes. Furthermore, clinical studies link osteoglycin to insulin resistance and cardiovascular disease. Osteoglycin may be a novel marker of a muscle, pancreatic, and bone axis. However, current evidence is limited and further research investigating osteoglycin in both a pre-clinical and a clinical setting is needed.
Topics: Animals; Biomarkers; Bone Density; Bone Remodeling; Cardiovascular Diseases; Cell Differentiation; Humans; Insulin Resistance; Intercellular Signaling Peptides and Proteins
PubMed: 31396918
DOI: 10.1007/s11914-019-00523-z -
Cardiovascular Diabetology Dec 2022Apolipoprotein C1 (apoC1) is a small size apolipoprotein whose exact role is not totally clarified but which seems to modulate significantly the metabolism of... (Review)
Review
Apolipoprotein C1 (apoC1) is a small size apolipoprotein whose exact role is not totally clarified but which seems to modulate significantly the metabolism of lipoproteins. ApoC1 is involved in the metabolism of triglyceride-rich lipoproteins by inhibiting the binding of very low density lipoproteins (VLDL) to VLDL-receptor (VLDL-R), to low density lipoprotein receptor (LDL-R) and to LDL receptor related protein (LRP), by reducing the activity of lipoprotein lipase (LPL) and by stimulating VLDL production, all these effects leading to increase plasma triglycerides. ApoC1 takes also part in the metabolism of high density lipoproteins (HDL) by inhibiting Cholesterol Ester Transfer Protein (CETP). The functionality of apoC1 on CETP activity is impaired in diabetes that might account, at least in part, for the increased plasma CETP activity observed in patients with diabetes. Its different effects on lipoprotein metabolism with a possible role in the modulation of inflammation makes the net impact of apoC1 on cardiometabolic risk difficult to figure out and apoC1 might be considered as pro-atherogenic or anti-atherogenic depending on the overall metabolic context. Making the link between total plasma apoC1 levels and the risk of cardio-metabolic diseases is difficult due to the high exchangeability of this small protein whose biological effects might depend essentially on its association with VLDL or HDL. The role of apoC1 in humans is not entirely elucidated and further studies are needed to determine its precise role in lipid metabolism and its possible pleiotropic effects on inflammation and vascular wall biology. In this review, we will present data on apoC1 structure and distribution among lipoproteins, on the effects of apoC1 on VLDL metabolism and HDL metabolism and we will discuss the possible links between apoC1, atherosclerosis and diabetes.
Topics: Humans; Apolipoprotein C-I; Atherosclerosis; Cholesterol Ester Transfer Proteins; Diabetes Mellitus; Inflammation; Lipoproteins, HDL; Lipoproteins, VLDL; Triglycerides
PubMed: 36471375
DOI: 10.1186/s12933-022-01703-5 -
Obesity Surgery Feb 2017Post-bariatric surgery may compromise nutritional status due to energy and protein intake restriction. (Review)
Review
BACKGROUND
Post-bariatric surgery may compromise nutritional status due to energy and protein intake restriction.
METHODS
Systematic review was performed to synthesize evidence on the amount of protein intake and its association with lean mass and serum proteins during at least 6 months following Roux-en-Y gastric bypass or sleeve gastrectomy.
RESULTS
Twelve studies (n = 739) were identified in the search. Protein intake below 60 g/day and significant lean mass loss were observed in majority of these studies. Of the four studies that measured association between protein intake and lean mass retention, only two supported this hypothesis.
CONCLUSION
There is insufficient evidence of the effect of dietary protein on serum protein levels. Further studies are needed to better estimate the protein intake that supports a healthy nutritional status in this population.
Topics: Bariatric Surgery; Blood Proteins; Body Mass Index; Dietary Proteins; Eating; Humans; Nutritional Status; Obesity, Morbid
PubMed: 27844254
DOI: 10.1007/s11695-016-2453-0