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Microbial Biotechnology Oct 2022There was inconsistent evidence regarding the use of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) for microorganism... (Meta-Analysis)
Meta-Analysis
There was inconsistent evidence regarding the use of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) for microorganism identification with/without antibiotic stewardship team (AST) and the clinical outcome of patients with bloodstream infections (BSI). In a systematic review and meta-analysis, we evaluated the effectiveness of rapid microbial identification by MALDI-TOF MS with and without AST on clinical outcomes. We searched PubMed and EMBASE databases from inception to 1 February 2022 to identify pre-post and parallel comparative studies that evaluated the use of MALDI-TOF MS for microorganism identification. Pooled effect estimates were derived using the random-effects model. Twenty-one studies with 14,515 patients were meta-analysed. Compared with conventional phenotypic methods, MALDI-TOF MS was associated with a 23% reduction in mortality (RR = 0.77; 95% CI: 0.66; 0.90; I = 35.9%; 13 studies); 5.07-h reduction in time to effective antibiotic therapy (95% CI: -5.83; -4.31; I = 95.7%); 22.86-h reduction in time to identify microorganisms (95% CI: -23.99; -21.74; I = 91.6%); 0.73-day reduction in hospital stay (95% CI: -1.30; -0.16; I = 53.1%); and US$4140 saving in direct hospitalization cost (95% CI: $-8166.75; $-113.60; I = 66.1%). No significant heterogeneity sources were found, and no statistical evidence for publication bias was found. Rapid pathogen identification by MALDI-TOF MS with or without AST was associated with reduced mortality and improved outcomes of BSI, and may be cost-effective among patients with BSI.
Topics: Anti-Bacterial Agents; Costs and Cost Analysis; Humans; Sepsis; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Time Factors
PubMed: 35921430
DOI: 10.1111/1751-7915.14124 -
Journal of Cachexia, Sarcopenia and... Jun 2024Proliferating cancer cells shift their metabolism towards glycolysis, even in the presence of oxygen, to especially generate glycolytic intermediates as substrates for...
BACKGROUND
Proliferating cancer cells shift their metabolism towards glycolysis, even in the presence of oxygen, to especially generate glycolytic intermediates as substrates for anabolic reactions. We hypothesize that a similar metabolic remodelling occurs during skeletal muscle hypertrophy.
METHODS
We used mass spectrometry in hypertrophying C2C12 myotubes in vitro and plantaris mouse muscle in vivo and assessed metabolomic changes and the incorporation of the [U-C]glucose tracer. We performed enzyme inhibition of the key serine synthesis pathway enzyme phosphoglycerate dehydrogenase (Phgdh) for further mechanistic analysis and conducted a systematic review to align any changes in metabolomics during muscle growth with published findings. Finally, the UK Biobank was used to link the findings to population level.
RESULTS
The metabolomics analysis in myotubes revealed insulin-like growth factor-1 (IGF-1)-induced altered metabolite concentrations in anabolic pathways such as pentose phosphate (ribose-5-phosphate/ribulose-5-phosphate: +40%; P = 0.01) and serine synthesis pathway (serine: -36.8%; P = 0.009). Like the hypertrophy stimulation with IGF-1 in myotubes in vitro, the concentration of the dipeptide l-carnosine was decreased by 26.6% (P = 0.001) during skeletal muscle growth in vivo. However, phosphorylated sugar (glucose-6-phosphate, fructose-6-phosphate or glucose-1-phosphate) decreased by 32.2% (P = 0.004) in the overloaded muscle in vivo while increasing in the IGF-1-stimulated myotubes in vitro. The systematic review revealed that 10 metabolites linked to muscle hypertrophy were directly associated with glycolysis and its interconnected anabolic pathways. We demonstrated that labelled carbon from [U-C]glucose is increasingly incorporated by ~13% (P = 0.001) into the non-essential amino acids in hypertrophying myotubes, which is accompanied by an increased depletion of media serine (P = 0.006). The inhibition of Phgdh suppressed muscle protein synthesis in growing myotubes by 58.1% (P < 0.001), highlighting the importance of the serine synthesis pathway for maintaining muscle size. Utilizing data from the UK Biobank (n = 450 243), we then discerned genetic variations linked to the serine synthesis pathway (PHGDH and PSPH) and to its downstream enzyme (SHMT1), revealing their association with appendicular lean mass in humans (P < 5.0e-8).
CONCLUSIONS
Understanding the mechanisms that regulate skeletal muscle mass will help in developing effective treatments for muscle weakness. Our results provide evidence for the metabolic rewiring of glycolytic intermediates into anabolic pathways during muscle growth, such as in serine synthesis.
Topics: Glucose; Muscle, Skeletal; Animals; Mice; Humans; Hypertrophy; Muscle Fibers, Skeletal; Insulin-Like Growth Factor I; Metabolomics
PubMed: 38742477
DOI: 10.1002/jcsm.13468 -
Drug Metabolism Reviews May 2015Synthetic cannabinoids (SC), originally developed as research tools, are now highly abused novel psychoactive substances. We present a comprehensive systematic review... (Review)
Review
Synthetic cannabinoids (SC), originally developed as research tools, are now highly abused novel psychoactive substances. We present a comprehensive systematic review covering in vivo and in vitro animal and human pharmacokinetics and analytical methods for identifying SC and their metabolites in biological matrices. Of two main phases of SC research, the first investigated therapeutic applications, and the second abuse-related issues. Administration studies showed high lipophilicity and distribution into brain and fat tissue. Metabolite profiling studies, mostly with human liver microsomes and human hepatocytes, structurally elucidated metabolites and identified suitable SC markers. In general, SC underwent hydroxylation at various molecular sites, defluorination of fluorinated analogs and phase II metabolites were almost exclusively glucuronides. Analytical methods are critical for documenting intake, with different strategies applied to adequately address the continuous emergence of new compounds. Immunoassays have different cross-reactivities for different SC classes, but cannot keep pace with changing analyte targets. Gas chromatography and liquid chromatography mass spectrometry assays - first for a few, then numerous analytes - are available but constrained by reference standard availability, and must be continuously updated and revalidated. In blood and oral fluid, parent compounds are frequently present, albeit in low concentrations; for urinary detection, metabolites must be identified and interpretation is complex due to shared metabolic pathways. A new approach is non-targeted HRMS screening that is more flexible and permits retrospective data analysis. We suggest that streamlined assessment of new SC's pharmacokinetics and advanced HRMS screening provide a promising strategy to maintain relevant assays.
Topics: Animals; Biotransformation; Brain; Cannabinoids; Chromatography, Liquid; Humans; Illicit Drugs; Liver; Mass Spectrometry; Molecular Structure; Organ Specificity; Substance Abuse Detection; Tandem Mass Spectrometry; Tissue Distribution
PubMed: 25853390
DOI: 10.3109/03602532.2015.1029635 -
ACS Infectious Diseases Oct 2017With heightened global concern of microbial drug resistance, advanced methods for early and accurate diagnosis of infection are urgently needed. Analysis of exhaled... (Review)
Review
With heightened global concern of microbial drug resistance, advanced methods for early and accurate diagnosis of infection are urgently needed. Analysis of exhaled breath volatile organic compounds (VOCs) toward detecting microbial infection potentially allows a highly informative and noninvasive alternative to current genomics and culture-based methods. We performed a systematic review of research literature reporting human and animal exhaled breath VOCs related to microbial infections. In this Review, we find that a wide range of breath sampling and analysis methods are used by researchers, which significantly affects interstudy method comparability. Studies either perform targeted analysis of known VOCs relating to an infection, or non-targeted analysis to obtain a global profile of volatile metabolites. In general, the field of breath analysis is still relatively immature, and there is much to be understood about the metabolic production of breath VOCs, particularly in a host where both commensal microflora as well as pathogenic microorganisms may be manifested in the airways. We anticipate that measures to standardize high throughput sampling and analysis, together with an increase in large scale collaborative international trials, will bring routine breath VOC analysis to improve diagnosis of infection closer to reality.
Topics: Animals; Bacterial Infections; Biomarkers; Breath Tests; Humans; Volatile Organic Compounds
PubMed: 28870074
DOI: 10.1021/acsinfecdis.7b00088 -
Plant Physiology and Biochemistry : PPB Nov 2023Microplastics (MPx) and nanoplastics (NPx) are increasingly accumulating in terrestrial ecosystems, heightening concerns about their potential adverse effects on human... (Review)
Review
Microplastics (MPx) and nanoplastics (NPx) are increasingly accumulating in terrestrial ecosystems, heightening concerns about their potential adverse effects on human health via the food chain. Techniques aimed at recovering the most challenging colloidal fractions of MPx and NPx, especially for analytical purposes, are limited. This systematic review emphasises the absence of a universal, efficient, and cost-effective analytical method as the primary hindrance to studying MPx and NPx in soil and plant samples. The study reveals that several methods, including density separation, organic matter removal, and filtration, are utilized to detect MPx or NPx in soil through vibrational spectroscopy and visual identification. Instruments such as Pyrolysis Gas Chromatography Mass Spectrometry (Py-GCMS), Transmission Electron Microscopy (TEM), Scanning Electron Microscopy (SEM), Fourier Transform Infrared (FTIR) Spectroscopy, and fluorescence microscopy are employed to identify MPx and NPx in plant tissue. In extraction procedures, organic solvents and sonication are used to isolate NPx from plant tissues, while Pyrolysis GC-MS quantifies the plastics. SEM and TEM serve to observe and characterize NPx within plant tissues. Additionally, FTIR and fluorescence microscopy are utilized to identify polymers of MPx and NPx based on their spectral characteristics and fluorescence signals. The findings from this review clarify the identification and quantification methods for MPx and NPx in soil and plant systems and provide a comprehensive methodology for assessing MPx/NPx in the environment.
Topics: Humans; Microplastics; Plastics; Soil; Ecosystem; Polymers; Water Pollutants, Chemical
PubMed: 37918078
DOI: 10.1016/j.plaphy.2023.108132 -
Clinical Toxicology (Philadelphia, Pa.) Sep 2023The opioid epidemic in the United States continues to result in an increasing number of deaths and is increasingly dominated by fentanyl and fentanyl analogs. As a... (Review)
Review
INTRODUCTION
The opioid epidemic in the United States continues to result in an increasing number of deaths and is increasingly dominated by fentanyl and fentanyl analogs. As a result, first responders are likely to come into contact with fentanyl-containing substances daily. Concerns persist regarding occupational exposure resulting in intoxication. We performed a systematic review to describe occupational illnesses from fentanyl and its analogs.
METHODS
We conducted a systematic review of the literature following the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to assess the danger of occupational exposure to fentanyl. The PubMed, EMBASE, Google Scholar, SCOPUS, CINAHL, and National Institute for Occupational Safety and Health databases were queried to identify occupational fentanyl exposures. Studies included were single case reports, case series, observational studies, controlled studies, and abstracts from scientific presentations. We reviewed articles meeting the eligibility criteria and abstracted outcome data. Outcomes included study design, number of study subjects and study demographics, description of exposure, personal protective equipment used, duration of symptoms, illness developed, medical evaluation performed, treatment provided, hospitalizations, deaths, drug testing performed, and any situation review performed to prevent illness, analytical confirmation of the identity of culprit agent, and concentrations of drug in serum/blood.
RESULTS
Our search yielded 454 citations after deduplication. After abstract and text review, 12 unique reports met the inclusion criteria. All identified studies were observational studies. Ten of the 12 were Health Hazard Evaluation reports from the National Institute for Occupational Safety and Health; two reports describe the same exposure case. There were no reported instances of comprehensive drug testing using liquid chromatography-mass spectrometry or gas chromatography-mass spectrometry in exposed first responders. Among first responders possibly exposed to fentanyl or fentanyl analogs, none were admitted to the hospital, and only three first responders received naloxone. The three officers who received naloxone lacked recommended personal protective equipment and had subjective improvement of symptoms following naloxone. There were no instances of severe respiratory depression requiring assisted ventilation or hospital admission. Among forensic laboratory technicians, only one instance of detectable concentrations of fentanyl in urine was reported, and there were no instances of symptomatic cases.
CONCLUSIONS
Among published reports of 27 first responders with symptoms after possible ambient fentanyl exposure, symptoms, recorded physical findings, and vital signs were inconsistent with acute opioid toxicity. Breaches in the recommended use of personal protective equipment appeared common. Only three persons received naloxone, although none had plausible effects of fentanyl. No suspected exposure to fentanyl led to hospitalization or death. Based on these low-quality data, there were no plausible opioid effects from ambient exposure to suspected fentanyl.
Topics: United States; Humans; Fentanyl; Analgesics, Opioid; Chromatography, Liquid; Databases, Factual; Naloxone
PubMed: 37988114
DOI: 10.1080/15563650.2023.2259087 -
Molecular Neurobiology Apr 2022Oxygen glucose deprivation (OGD) of brain cells is the commonest in vitro model of ischemic stroke that is used extensively for basic and preclinical stroke research.... (Review)
Review
Oxygen glucose deprivation (OGD) of brain cells is the commonest in vitro model of ischemic stroke that is used extensively for basic and preclinical stroke research. Protein mass spectrometry is one of the most promising and rapidly evolving technologies in biomedical research. A systems-level understanding of cell-type-specific responses to oxygen and glucose deprivation without systemic influence is a prerequisite to delineate the response of the neurovascular unit following ischemic stroke. In this systematic review, we summarize the proteomics studies done on different OGD models. These studies have followed an expression or interaction proteomics approach. They have been primarily used to understand the cellular pathophysiology of ischemia-reperfusion injury or to assess the efficacy of interventions as potential treatment options. We compile the limitations of OGD model and downstream proteomics experiment. We further show that despite having limitations, several proteins shortlisted as altered in in vitro OGD-proteomics studies showed comparable regulation in ischemic stroke patients. This showcases the translational potential of this approach for therapeutic target and biomarker discovery. We next discuss the approaches that can be adopted for cell-type-specific validation of OGD-proteomics results in the future. Finally, we briefly present the research questions that can be addressed by OGD-proteomics studies using emerging techniques of protein mass spectrometry. We have also created a web resource compiling information from OGD-proteomics studies to facilitate data sharing for community usage. This review intends to encourage preclinical stroke community to adopt a hypothesis-free proteomics approach to understand cell-type-specific responses following ischemic stroke.
Topics: Brain Ischemia; Glucose; Humans; Ischemic Stroke; Oxygen; Proteomics; Reperfusion Injury; Stroke
PubMed: 35080759
DOI: 10.1007/s12035-022-02745-2 -
Journal of Pharmaceutical and... Sep 2023Glycosylation is a crucial attribute for biotherapeutics with significant impacts on quality, stability, safety, immunogenicity, pharmacokinetics, and efficacy.... (Review)
Review
Glycosylation is a crucial attribute for biotherapeutics with significant impacts on quality, stability, safety, immunogenicity, pharmacokinetics, and efficacy. Therefore, to ensure consistent glycosylation, a systematic review of biotherapeutics is absolutely required including the variable glycan structure (micro-heterogeneity) and different occupancy at individual site (macro-heterogeneity) from drug design to upstream and downstream bioprocesses. Various methods have been used for glyco-characterization of biotherapeutics at the glycan, glycopeptide, and intact protein levels. In particular, intact protein analysis is considered a facile and rapid glycoform monitoring approach used throughout the product development lifecycle to determine suitable glycosylation lead candidates and reproducible product quality. However, intact glycoform characterization of diverse and complex biotherapeutics with multiple N- and O-glycosylation sites can be very challenging. To address this, a robust analytical platform that enables rapid and accurate characterization of a biotherapeutics with highly complex multiple glycosylation using two-step intact glycoform mass spectrometry has been developed. We used darbepoetin alfa, a second-generation EPO bearing multiple N- and O-glycosylation sites, as a model biotherapeutics to obtain integrated information on glycan heterogeneity and site occupancy through step-by-step MS of intact protein and enzyme-treated protein. In addition, we performed a comparative assessment of the heterogeneity from different products, confirming that our new method can efficiently evaluate glycosylation equivalence. This new strategy provides rapid and accurate information on the degree of glycosylation of a therapeutic glycoprotein with multiple glycosylation, which can be used to assess glycosylation similarity between batches and between biosimilar and reference during development and production.
Topics: Glycosylation; Darbepoetin alfa; Mass Spectrometry; Proteins; Polysaccharides
PubMed: 37393692
DOI: 10.1016/j.jpba.2023.115558 -
Cancer Medicine Jul 2022Salivary diagnostics and their utility as a nonaggressive approach for breast cancer diagnosis have been extensively studied in recent years. This meta-analysis assesses... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Salivary diagnostics and their utility as a nonaggressive approach for breast cancer diagnosis have been extensively studied in recent years. This meta-analysis assesses the diagnostic value of salivary biomarkers in differentiating between patients with breast cancer and controls.
METHODS
We conducted a meta-analysis and systematic review of studies related to salivary diagnostics published in PubMed, EMBASE, Scopus, Ovid, Science Direct, Web of Science (WOS), and Google Scholar. The articles were chosen utilizing inclusion and exclusion criteria, as well as assessing their quality. Specificity and sensitivity, along with negative and positive likelihood ratios (NLR and PLR) and diagnostic odds ratio (DOR), were calculated based on random- or fixed-effects model. Area under the curve (AUC) and summary receiver-operating characteristic (SROC) were plotted and evaluated, and Fagan's Nomogram was evaluated for clinical utility.
RESULTS
Our systematic review and meta-analysis included 14 papers containing 121 study units with 8639 adult subjects (4149 breast cancer patients and 4490 controls without cancer). The pooled specificity and sensitivity were 0.727 (95% CI: 0.713-0.740) and 0.717 (95% CI: 0.703-0.730), respectively. The pooled NLR and PLR were 0.396 (95% CI: 0.364-0.432) and 2.597 (95% CI: 2.389-2.824), respectively. The pooled DOR was 7.837 (95% CI: 6.624-9.277), with the AUC equal to 0.801. The Fagan's nomogram showed post-test probabilities of 28% and 72% for negative and positive outcomes, respectively. We also conducted subgroup analyses to determine specificity, sensitivity, DOR, PLR, and NLR based on the mean age of patients (≤52 or >52 years old), saliva type (stimulated and unstimulated saliva), biomarker measurement method (mass spectrometry [MS] and non-MS measurement methods), sample size (≤55 or >55), biomarker type (proteomics, metabolomics, transcriptomics and proteomics, and reagent-free biophotonic), and nations.
CONCLUSION
Saliva, as a noninvasive biomarker, has the potential to accurately differentiate breast cancer patients from healthy controls.
Topics: Adult; Biomarkers; Breast Neoplasms; Female; Humans; Middle Aged; Odds Ratio; ROC Curve; Sensitivity and Specificity
PubMed: 35315584
DOI: 10.1002/cam4.4640 -
Clinical Oral Investigations Mar 2018The objective of the study was to conduct a systematic review of the literature assessing potential salivary biomarkers of oral cancer and pre-cancer and discuss... (Review)
Review
OBJECTIVE
The objective of the study was to conduct a systematic review of the literature assessing potential salivary biomarkers of oral cancer and pre-cancer and discuss emerging issues and challenges in relation to oral cancer and pre-cancer diagnostics.
MATERIALS AND METHODS
Search for articles involved the Medline, PubMed, and EMBASE. Specific terms were used from January 1995 to March 2017 by three experts.
RESULTS
This search collected 270 articles, of which 105 articles such as reviews, case reports, news, letter to editor, etc. in first round and 117 articles such as publications in other languages than English, non-human studies, etc. were excluded. The remaining 48 articles considered analyzing whole saliva as well as specific gland saliva. Thirty-one studies considered oral stimuli such as eating, drinking, and oral hygiene practices for varied periods of time prior to sample collection. The time of collection of saliva was morning in most studies, but the exact time of collection was not mentioned. Three studies showed to have evaluated the whole saliva without centrifugation. Two-dimensional gel electrophoresis and tandem mass spectrometry were the most commonly used methods. Most of the potential salivary biomarkers of oral cancer are salivary proteins.
CONCLUSION
Combination approach of salivary biomarkers could be used as screening tool to improve early detection and diagnostic precision of oral pre-cancer and cancer.
CLINICAL RELEVANCE
The current findings are of importance for clinicians and researchers to mitigate the challenges in salivary-based diagnosis of oral cancer and to evaluate reliable, specific, and sensitive salivary biomarkers for oral pre-cancer and cancer diagnosis.
Topics: Biomarkers, Tumor; Early Detection of Cancer; Electrophoresis, Gel, Two-Dimensional; Humans; Mouth Neoplasms; Precancerous Conditions; Saliva; Tandem Mass Spectrometry
PubMed: 29344805
DOI: 10.1007/s00784-018-2337-x