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Biomolecules Nov 2023Mitochondria are ancient endosymbiotic double membrane organelles that support a wide range of eukaryotic cell functions through energy, metabolism, and cellular... (Review)
Review
Mitochondria are ancient endosymbiotic double membrane organelles that support a wide range of eukaryotic cell functions through energy, metabolism, and cellular control. There are over 1000 known proteins that either reside within the mitochondria or are transiently associated with it. These mitochondrial proteins represent a functional subcellular protein network (mtProteome) that is encoded by mitochondrial and nuclear genomes and significantly varies between cell types and conditions. In neurons, the high metabolic demand and differential energy requirements at the synapses are met by specific modifications to the mtProteome, resulting in alterations in the expression and functional properties of the proteins involved in energy production and quality control, including fission and fusion. The composition of mtProteomes also impacts the localization of mitochondria in axons and dendrites with a growing number of neurodegenerative diseases associated with changes in mitochondrial proteins. This review summarizes the findings on the composition and properties of mtProteomes important for mitochondrial energy production, calcium and lipid signaling, and quality control in neural cells. We highlight strategies in mass spectrometry (MS) proteomic analysis of mtProteomes from cultured cells and tissue. The research into mtProteome composition and function provides opportunities in biomarker discovery and drug development for the treatment of metabolic and neurodegenerative disease.
Topics: Humans; Proteome; Neurodegenerative Diseases; Proteomics; Mitochondria; Neurons; Mitochondrial Proteins
PubMed: 38002320
DOI: 10.3390/biom13111638 -
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 -
Nucleic Acids Research Jun 2022At the time of writing, although siRNA therapeutics are approved for human use, no official regulatory guidance specific to this modality is available. In the absence of...
At the time of writing, although siRNA therapeutics are approved for human use, no official regulatory guidance specific to this modality is available. In the absence of guidance, preclinical development for siRNA followed a hybrid of the small molecule and biologics guidance documents. However, siRNA differs significantly from small molecules and protein-based biologics in its physicochemical, absorption, distribution, metabolism and excretion properties, and its mechanism of action. Consequently, certain reports typically included in filing packages for small molecule or biologics may benefit from adaption, or even omission, from an siRNA filing. In this white paper, members of the 'siRNA working group' in the IQ Consortium compile a list of reports included in approved siRNA filing packages and discuss the relevance of two in vitro reports-the plasma protein binding evaluation and the drug-drug interaction risk assessment-to support siRNA regulatory filings. Publicly available siRNA approval packages and the literature were systematically reviewed to examine the role of siRNA plasma protein binding and drug-drug interactions in understanding pharmacokinetic/pharmacodynamic relationships, safety and translation. The findings are summarized into two decision trees to help guide industry decide when in vitro siRNA plasma protein binding and drug-drug interaction studies are warranted.
Topics: Biological Products; Blood Proteins; Decision Trees; Drug Interactions; Humans; Protein Binding; RNA, Small Interfering
PubMed: 35687098
DOI: 10.1093/nar/gkac456 -
International Journal of Molecular... Apr 2023Appetite dysregulation is one of the factors contributing to anorexia, bulimia nervosa, obesity, and diabetes. Essential oils or fragrant compounds have been proven to... (Review)
Review
Appetite dysregulation is one of the factors contributing to anorexia, bulimia nervosa, obesity, and diabetes. Essential oils or fragrant compounds have been proven to regulate food intake and energy expenditure; hence, this study aimed to summarize their effects on appetite and the underlying mechanisms. The PubMed and Web of Science databases were searched until July 2022. Only two of the 41 studies were performed clinically, and the remaining 39 used animal models. Oral administration was the most common route, and a dosage range of 100-2000 mg/kg for mice or 2-32 mg/kg for rats was applied, with a duration of 12 days to 4 weeks, followed by inhalation (10-10 mg/cage or 10-10 mg/cm within 1 h). Approximately 11 essential oil samples and 22 fragrant compounds were found to increase appetite, while 12 essential oils and seven compounds decreased appetite. These fragrant components can exert appetite-regulating effects via leptin resistance, the activity of sympathetic/parasympathetic nerves, or the mRNA expression of neuropeptide Y (NPY)/agouti-related protein (AgRP), cocaine- and amphetamine-regulated transcript (CART)/proopiomelanocortin (POMC) in the hypothalamus. Fragrance memory and cognitive processes may also play roles in appetite regulation. The findings of this study accentuate the potential of essential oils and fragrant compounds to regulate appetite and eating disorders.
Topics: Rats; Mice; Animals; Appetite; Oils, Volatile; Nerve Tissue Proteins; Neuropeptide Y; Hypothalamus; Leptin; Appetite Regulation; Agouti-Related Protein; Eating
PubMed: 37175666
DOI: 10.3390/ijms24097962 -
The Journal of Nutrition Mar 2016Protein intake may influence important health outcomes in later life. (Review)
Review
BACKGROUND
Protein intake may influence important health outcomes in later life.
OBJECTIVE
The objective of this study was to investigate current evidence on the effects of infant formulas and follow-on formulas with different protein concentrations on infants' and children's growth, body composition, and later risk of overweight and obesity.
METHODS
In this systematic review, we searched electronic databases (including MEDLINE, Embase, and the Cochrane Library) up until November 2014 for randomized controlled trials (RCTs). Eligible studies had to include children aged 0-3 y who represented the general population and were fed cow milk-based infant formulas with variations in protein concentration. Control groups received lower-protein cow milk-based formulas (as defined by the authors). The primary outcomes were growth, overweight, obesity, and adiposity. Various time points for outcomes assessment were accepted for inclusion. If possible, a meta-analysis was performed.
RESULTS
Twelve RCTs met our inclusion criteria. Different formula protein concentrations did not affect linear growth other than a transient effect on mean length at 3 mo observed in a meta-analysis of 4 studies (mean difference, - 0.27 cm; 95% CI: -0.52, -0.02). Lower mean weight and weight z scores obtained from the infants fed lower-protein formulas were observed only from 6 to 12 mo of age. Data from one large RCT showed that consumption of a lower-protein infant formula may reduce body mass index at 12 mo of age and later (12 mo, 24 mo, and 6y) and the risk of obesity at 6 y. Effects on body composition remained unclear.
CONCLUSIONS
The current evidence is insufficient for assessing the effects of reducing the protein concentration in infant formulas on long-term outcomes, but, if confirmed, this could be a promising intervention for reducing the risk of overweight and obesity in children. In view of the limited available evidence, more studies replicating effects on long-term health outcomes are needed.
Topics: Animals; Body Composition; Body Mass Index; Body Weight; Child; Child, Preschool; Databases, Factual; Dietary Proteins; Humans; Infant; Infant Formula; Milk; Obesity; Randomized Controlled Trials as Topic; Risk Factors
PubMed: 26865649
DOI: 10.3945/jn.115.223651 -
Cureus Mar 2023A ketogenic diet (KD), more commonly called a "keto" diet, is a dietary regime that focuses on reducing carbohydrates and replacing them with healthy fats. It has... (Review)
Review
A ketogenic diet (KD), more commonly called a "keto" diet, is a dietary regime that focuses on reducing carbohydrates and replacing them with healthy fats. It has proven to improve health and has resurfaced as a trendy weight loss method. Keto, in simple terms, works by mimicking starvation and forcing the body to utilize and deplete fat as its core energy source instead of its usual source of glucose (sugar). More technically, it gives ignition to a process called 'ketosis'. Ketosis is the process of generation of ketone bodies when the liver metabolizes fat. There are several versions of this diet, each of which addresses slightly variable issues as well as hones unique requirements. Individuals will require a unique combination of fat, carbohydrates, and protein depending on their genetic and physical makeup. The advantages and hazards of using the KD to manage obesity are examined in this review of the literature.
PubMed: 37123756
DOI: 10.7759/cureus.36720 -
Frontiers in Immunology 2023Novel biomarkers of inflammation and oxidative stress might enhance the early recognition, management, and clinical outcomes of patients with rheumatic diseases (RDs).... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Novel biomarkers of inflammation and oxidative stress might enhance the early recognition, management, and clinical outcomes of patients with rheumatic diseases (RDs). We assessed the available evidence regarding the pathophysiological role of neopterin, the oxidation product of 7,8-dihydroneopterin, a pteridine generated in macrophages activated by interferon-γ, by conducting a systematic review and meta-analysis of studies reporting its concentrations in biological fluids in RD patients and healthy controls.
METHODS
We searched electronic databases for relevant articles published between inception and 31 August 2023. The risk of bias and the certainty of evidence were assessed using the Joanna Briggs Institute Critical Appraisal Checklist and the Grades of Recommendation, Assessment, Development and Evaluation Working Group system, respectively.
RESULTS
In 37 studies, when compared to healthy controls, RD patients had significantly higher concentrations of neopterin both in plasma or serum (standard mean difference, SMD=1.31, 95% CI 1.01 to 1.61; p<0.001; moderate certainty of evidence) and in the urine (SMD=1.65, 95% CI 0.86 to 2.43, p<0.001; I = 94.2%, p<0.001; low certainty of evidence). The results were stable in sensitivity analysis. There were non-significant associations in meta-regression and subgroup analysis between the effect size and age, male to female ratio, year of publication, sample size, RD duration, C-reactive protein, erythrocyte sedimentation rate, specific type of RD, presence of connective tissue disease, analytical method used, or biological matrix investigated (plasma . serum). By contrast, the effect size was significantly associated with the geographical area in studies assessing serum or plasma and with the type of RD in studies assessing urine.
DISCUSSION
Pending additional studies that also focus on early forms of disease, our systematic review and meta-analysis supports the proposition that neopterin, a biomarker of inflammation and oxidative stress, can be useful for the identification of RDs. (PROSPERO registration number: CRD42023450209).
SYSTEMATIC REVIEW REGISTRATION
PROSPERO, identifier CRD42023450209.
Topics: Humans; Male; Female; Neopterin; Inflammation; Oxidation-Reduction; Oxidative Stress; Rheumatic Diseases; Biomarkers
PubMed: 37799718
DOI: 10.3389/fimmu.2023.1271383 -
Brain, Behavior, and Immunity Mar 2024While genetic and cohort studies suggest immune and reduction/oxidation (redox) alterations occur in psychosis, less is known about potential alterations in children and... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
While genetic and cohort studies suggest immune and reduction/oxidation (redox) alterations occur in psychosis, less is known about potential alterations in children and adolescents.
METHODS
We conducted a systematic review to identify immune and redox biomarker studies in children and adolescents (mean age ≤ 18 years old) across the psychosis spectrum: from psychotic like experiences, which are common in children, to threshold psychotic disorders like schizophrenia. We conducted meta-analyses when at least three studies measured the same biomarker.
RESULTS
The systematic review includes 38 pediatric psychosis studies. The meta-analyses found that youth with threshold psychotic disorders had higher neutrophil/lymphocyte ratio (Hedge's g = 0.40, 95 % CI 0.17 - 0.64), tumor necrosis factor (Hedge's g = 0.38, 95 % CI 0.06 - 0.69), C-reactive protein (Hedge's g = 0.38, 95 % CI 0.05 - 0.70), interleukin-6 (Hedge's g = 0.35; 95 % CI 0.11 - 0.64), and total white blood cell count (Hedge's g = 0.29, 95 % CI 0.12 - 0.46) compared to youth without psychosis. Other immune and oxidative stress meta-analytic findings were very heterogeneous.
CONCLUSION
Results from several studies are consistent with the hypothesis that signals often classified as "proinflammatory" are elevated in threshold pediatric psychotic disorders. Data are less clear for immune markers in subthreshold psychosis and redox markers across the subthreshold and threshold psychosis spectrum. Immune and redox biomarker intervention studies are lacking, and research investigating interventions targeting the immune system in threshold pediatric psychosis is especially warranted.
Topics: Adolescent; Humans; Child; Psychotic Disorders; Biomarkers; C-Reactive Protein; Interleukin-6; Oxidative Stress
PubMed: 38141839
DOI: 10.1016/j.bbi.2023.12.019 -
Bone Feb 2022Fibrous dysplasia (FD) is a rare genetic bone disorder resulting in an overproduction of cAMP leading to a structurally unsound tissue, caused by a genetic mutation in...
BACKGROUND
Fibrous dysplasia (FD) is a rare genetic bone disorder resulting in an overproduction of cAMP leading to a structurally unsound tissue, caused by a genetic mutation in the guanine nucleotide-binding protein gene (GNAS). In order to better understand this disease, several animal models have been developed with different strategies and features.
OBJECTIVE
Conduct a systematic review to analyze and compare animal models with the causative mutation and features of FD.
METHODS
A PRISMA search was conducted in Scopus, PubMed, and Web of Science. Studies reporting an in vivo model of FD that expressed the causative mutation were included for analysis. Models without the causative mutation, but developed an FD phenotype and models of FD cell implantation were included for subanalysis.
RESULTS
Seven unique models were identified. The models were assessed and compared for their face validity, construct validity, mosaicism, and induction methods. This was based on the features of clinical FD that were reported within the categories of: macroscopic features, imaging, histology and histomorphometry, histochemical and cellular markers, and blood/urine markers.
LIMITATIONS
None of the models reported all features of FD and some features were only reported in one model. This made comparing models a challenge, but indicates areas where further research is necessary.
CONCLUSION
The benefits and disadvantages of every model were assessed from a practical and scientific standpoint. While all published reports lacked complete data, the models have nonetheless informed our understanding of FD and provided meaningful information to guide researchers in bench and clinical research.
Topics: Animals; Bone and Bones; Fibrous Dysplasia of Bone; GTP-Binding Protein alpha Subunits, Gs; GTP-Binding Proteins; Mutation
PubMed: 34875396
DOI: 10.1016/j.bone.2021.116270 -
Disease Markers 2015The diagnostic value of serum HE4 in patients with lung cancer remains controversial. Thus, we performed a systematic review and meta-analysis to assess the diagnostic... (Meta-Analysis)
Meta-Analysis Review
The diagnostic value of serum HE4 in patients with lung cancer remains controversial. Thus, we performed a systematic review and meta-analysis to assess the diagnostic accuracy of serum HE4 for lung cancer. We conducted a comprehensive literature search in PubMed, EMBASE, Chinese National Knowledge Infrastructure (CNKI), and WANFANG databases between Jan. 1966 and Nov. 2014. The diagnostic sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and summary receiver operating characteristic curve (SROC) were pooled by Meta-DiSc 1.4 software. A total of seven articles including 715 cases and 549 controls were included for analysis. The summary estimates for serum HE4 in the diagnosis of lung cancer in these studies were pooled SEN 0.72 (95% CI: 0.68-0.75), SPE 0.85 (95% CI: 0.81-0.88), PLR 4.68 (95% CI: 3.23-6.78), NLR 0.31 (95% CI: 0.24-0.39), and DOR 17.14 (95% CI: 9.72-30.20), and the area under the curve (AUC) was 0.8557. This meta-analysis indicated that serum HE4 is a potential tool in the diagnosis of lung cancer. In addition, considering the high heterogeneity and potential publication bias, further studies with rigorous design and large sample size are needed in the future.
Topics: Biomarkers, Tumor; Case-Control Studies; Humans; Lung Neoplasms; Proteins; Sensitivity and Specificity; WAP Four-Disulfide Core Domain Protein 2
PubMed: 25873748
DOI: 10.1155/2015/352670