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Journal of Clinical Medicine Jun 2024Disorders of mucociliary clearance, such as cystic fibrosis (CF), primary ciliary dyskinesia (PCD) and bronchiectasis of unknown origin, are characterised by periods... (Review)
Review
Disorders of mucociliary clearance, such as cystic fibrosis (CF), primary ciliary dyskinesia (PCD) and bronchiectasis of unknown origin, are characterised by periods with increased respiratory symptoms, referred to as pulmonary exacerbations. These exacerbations are hard to predict and associated with lung function decline and the loss of quality of life. To optimise treatment and preserve lung function, there is a need for non-invasive and reliable methods of detection. Breath analysis might be such a method. We systematically reviewed the existing literature on breath analysis to detect pulmonary exacerbations in mucociliary clearance disorders. Extracted data included the study design, technique of measurement, definition of an exacerbation, identified compounds and diagnostic accuracy. Out of 244 identified articles, 18 were included in the review. All studies included patients with CF and two also with PCD. Age and the definition of exacerbation differed between the studies. There were five that measured volatile organic compounds (VOCs) in exhaled breath using gas chromatography with mass spectrometry, two using an electronic nose and eleven measured organic compounds in exhaled breath condensate. Most studies showed a significant correlation between pulmonary exacerbations and one or multiple compounds, mainly hydrocarbons and cytokines, but the validation of these results in other studies was lacking. The detection of pulmonary exacerbations by the analysis of compounds in exhaled breath seems possible but is not near clinical application due to major differences in results, study design and the definition of an exacerbation. There is a need for larger studies, with a longitudinal design, international accepted definition of an exacerbation and validation of the results in independent cohorts.
PubMed: 38929901
DOI: 10.3390/jcm13123372 -
Experimental and Therapeutic Medicine Jul 2024The present study aimed to conduct a comprehensive meta-analysis to assess the diagnostic value of fluorometric assays and tandem mass spectrometry (MS/MS) for...
The present study aimed to conduct a comprehensive meta-analysis to assess the diagnostic value of fluorometric assays and tandem mass spectrometry (MS/MS) for hyperphenylalaninemia (HPA) and its subtypes. The PubMed, Embase and Cochrane Library databases were searched from inception to October 2023. The present study included studies that reported the newborn screening and genetic features of patients with HPA and excluded duplicate publications, studies without full text, studies with incomplete information, studies from which it was not possible to extract data, animal experiments, reviews and systematic reviews. STATA 15.1 was used to analyze the data. The pooled results revealed that 0.04% [95% confidence interval (CI): 0.019-0.069] of neonatal HPA fluorometric assays and MS/MS. The positive predictive value (PPV) of neonatal HPA screening using fluorometric assays and tandem mass spectrometry was 31.7% (95% CI: 19.6-45.2). Notably, the PPV of neonatal HPA screening using fluorometric assays was 8.3% (95% CI: 7.1-9.6), while the PPV of neonatal HPA screening using tandem mass spectrometry was 31.8% (95% CI: 16.4-49.4). Additionally, the pooled results showed that the incidence of tetrahydrobiopterin deficiency (BH4D) in HPA patients was 12.43% (95% CI: 3.28-25.75) and the incidence of phenylalanine hydroxylase deficiency (PAHD) in HPA patients was 88.65% (95% CI: 78.84-95.86). Newborn screening is an effective method for the early detection of HPA and MS/MS has a greater PPA than fluorometric assays for diagnosing HPA. In addition, in the screening of HPA, the proportion of HPA patients with PAHD was significantly higher than that of patients with BH4D.
PubMed: 38800050
DOI: 10.3892/etm.2024.12566 -
Lipids in Health and Disease May 2024Cancer prognosis remains a critical clinical challenge. Lipidomic analysis via mass spectrometry (MS) offers the potential for objective prognostic prediction,... (Review)
Review
Cancer prognosis remains a critical clinical challenge. Lipidomic analysis via mass spectrometry (MS) offers the potential for objective prognostic prediction, leveraging the distinct lipid profiles of cancer patient-derived specimens. This review aims to systematically summarize the application of MS-based lipidomic analysis in prognostic prediction for cancer patients. Our systematic review summarized 38 studies from the past decade that attempted prognostic prediction of cancer patients through lipidomics. Commonly analyzed cancers included colorectal, prostate, and breast cancers. Liquid (serum and urine) and tissue samples were equally used, with liquid chromatography-tandem MS being the most common analytical platform. The most frequently evaluated prognostic outcomes were overall survival, stage, and recurrence. Thirty-eight lipid markers (including phosphatidylcholine, ceramide, triglyceride, lysophosphatidylcholine, sphingomyelin, phosphatidylethanolamine, diacylglycerol, phosphatidic acid, phosphatidylserine, lysophosphatidylethanolamine, lysophosphatidic acid, dihydroceramide, prostaglandin, sphingosine-1-phosphate, phosphatidylinosito, fatty acid, glucosylceramide and lactosylceramide) were identified as prognostic factors, demonstrating potential for clinical application. In conclusion, the potential for developing lipidomics in cancer prognostic prediction was demonstrated. However, the field is still nascent, necessitating future studies for validating and establishing lipid markers as reliable prognostic tools in clinical practice.
Topics: Humans; Prognosis; Neoplasms; Lipidomics; Biomarkers, Tumor; Mass Spectrometry; Female; Lipids; Male; Breast Neoplasms; Prostatic Neoplasms; Lysophospholipids; Colorectal Neoplasms
PubMed: 38796445
DOI: 10.1186/s12944-024-02121-0 -
Breast Cancer Research and Treatment Jul 2024Vaginal oestrogens can be used to treat genitourinary symptoms in women with early breast cancer. Studies evaluating vaginal oestrogens have commonly measured serum...
PURPOSE
Vaginal oestrogens can be used to treat genitourinary symptoms in women with early breast cancer. Studies evaluating vaginal oestrogens have commonly measured serum oestrogen levels as a surrogate marker of safety, but methods vary. We sought to summarise the data on serum oestrogen measurement in women with breast cancer using vaginal oestrogens to better understand the methods, levels and reliability.
METHODS
We searched Medline, Embase, CENTRAL, SCOPUS and CINAHL from inception to October 2023 for clinical studies where serum oestrogen was measured in women with a history of early breast cancer using vaginal oestrogens. Studies with a reported testing methodology were included.
RESULTS
Nine studies met the inclusion criteria for this systematic review. Methods used to measure oestradiol and oestriol in selected studies included mass spectrometry and immunoassays; several studies used more than one with variable concordance. Mass spectrometry detected oestradiol levels down to a lower limit between 1.0 pg/mL and 3.0 pg/mL. Immunoassays such as ELISA (enzyme-linked immunosorbent assay), ECLIA (enhanced chemiluminiscence immunoassay) and RIA (radioimmunoassay) had lower detection limits ranging between 0.8 pg/mL and 10 pg/mL. Studies were heterogeneous in testing techniques used, timing of testing, and the population including with subsequent varying results in the effect on oestrogens reported.
CONCLUSIONS
Adopting consistent and standardised methods of measuring oestrogens in clinical trials involving women with early breast cancer on vaginal oestrogens is critical. Serum oestrogens are used as a surrogate marker of safety in this population, and good-quality data are necessary to enable clinicians and patients to feel confident in prescribing and taking vaginal oestrogens. Mass spectrometry, although more expensive, gives more reliable results when dealing with very low levels of oestrogens often found in women on aromatase inhibitors, compared to immunoassays.
Topics: Female; Humans; Administration, Intravaginal; Breast Neoplasms; Cancer Survivors; Estradiol; Estriol; Estrogens; Vagina
PubMed: 38780887
DOI: 10.1007/s10549-024-07364-0 -
Psychoneuroendocrinology Aug 2024Allopregnanolone (ALLO) is a metabolite of progesterone and a neuroactive steroid hormone. As a positive allosteric modulator of gamma-aminobutyric acid (GABA)...
BACKGROUND
Allopregnanolone (ALLO) is a metabolite of progesterone and a neuroactive steroid hormone. As a positive allosteric modulator of gamma-aminobutyric acid (GABA) receptors, ALLO seems to have antidepressant and anxiolytic effects, and was therefore approved as a specific medication for the treatment of postpartum depression in 2019. Despite the growing number of publications investigating ALLO levels, results on the biological and psychological correlates in the peripartum period remain inconsistent, possibly due to methodological challenges regarding measurement. To date, however, there is no systematic review examining the correlates, concentrations, and challenges in measuring ALLO in peripartum women.
METHOD
A systematic literature search of PubMed and PsycINFO was conducted in August 2023. Original research articles that measured ALLO concentrations in peripartum women were included. Reports were excluded if they were not original research, included non-human subjects, did not include peripartum women, did not include ALLO measurement as an outcome, included (pharmacological) interventions, constituted method validations, or used the same cohort as another study.
RESULTS
The literature search yielded 234 articles, and two articles were identified from other sources. After full-text screening, 19 articles (N = 1401) met the inclusion criteria, of which seven focused on biological correlates of ALLO and 12 on mood correlates. Of the latter, six found no association between ALLO and mood, four found a negative association, and two found a positive association. Overall, the results show an increase in ALLO levels during pregnancy and a decrease after birth, with levels then remaining low until six months postpartum. ALLO was most commonly measured in blood plasma and by gas chromatography-mass spectrometry (GC-MS). A significant matrix effect was found for blood serum and a significant method effect for radioimmunoassays (RIAs). A significant effect of time of measurement was found.
CONCLUSION
ALLO measurement shows method and matrix effects. ALLO levels are higher when measured in serum compared to in plasma, and when measured using RIA compared to other methods. Time of measurement, study design, and standardization of measurement also influence the reliability of measurement and the interpretation of results.
Topics: Humans; Pregnanolone; Female; Peripartum Period; Pregnancy; Depression, Postpartum; Adult
PubMed: 38759520
DOI: 10.1016/j.psyneuen.2024.107081 -
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 -
Asian Journal of Urology Apr 2024Metabolomics has been extensively utilized in bladder cancer (BCa) research, employing mass spectrometry and nuclear magnetic resonance spectroscopy to compare various... (Review)
Review
OBJECTIVE
Metabolomics has been extensively utilized in bladder cancer (BCa) research, employing mass spectrometry and nuclear magnetic resonance spectroscopy to compare various variables (tissues, serum, blood, and urine). This study aimed to identify potential biomarkers for early BCa diagnosis.
METHODS
A search strategy was designed to identify clinical trials, descriptive and analytical observational studies from databases such as Medline, Embase, Cochrane Central Register of Controlled Trials, and Latin American and Caribbean Literature in Health Sciences. Inclusion criteria comprised studies involving BCa tissue, serum, blood, or urine profiling using widely adopted metabolomics techniques like mass spectrometry and nuclear magnetic resonance. Primary outcomes included description of metabolites and metabolomics profiling in BCa patients and the association of metabolites and metabolomics profiling with BCa diagnosis compared to control patients. The risk of bias was assessed using the Quality Assessment of Studies of Diagnostic Accuracy.
RESULTS
The search strategy yielded 2832 studies, of which 30 case-control studies were included. Urine was predominantly used as the primary sample for metabolite identification. Risk of bias was often unclear inpatient selection, blinding of the index test, and reference standard assessment, but no applicability concerns were observed. Metabolites and metabolomics profiles associated with BCa diagnosis were identified in glucose, amino acids, nucleotides, lipids, and aldehydes metabolism.
CONCLUSION
The identified metabolites in urine included citric acid, valine, tryptophan, taurine, aspartic acid, uridine, ribose, phosphocholine, and carnitine. Tissue samples exhibited elevated levels of lactic acid, amino acids, and lipids. Consistent findings across tissue, urine, and serum samples revealed downregulation of citric acid and upregulation of lactic acid, valine, tryptophan, taurine, glutamine, aspartic acid, uridine, ribose, and phosphocholine.
PubMed: 38680576
DOI: 10.1016/j.ajur.2022.11.005 -
European Journal of Clinical... Jun 2024Oligella is an uncommon Gram-negative coccobacillus that was first thought to belong to the urogenital tract. The genus Oligella comprises two species that were... (Review)
Review
BACKGROUND
Oligella is an uncommon Gram-negative coccobacillus that was first thought to belong to the urogenital tract. The genus Oligella comprises two species that were recovered from various samples worldwide.
METHODS
We perform a systematic review focusing on Oligella microbiological characteristics, habitat, role in Human microbiome and infection, and antimicrobial susceptibility.
RESULTS
In humans, Oligella is mainly found as part of the microbiome of individuals with predisposing conditions. Oligella were also associated with invasive infections in patients with underlying diseases. Nevertheless, their prevalence remains to determine. Oligella culture requires up to 48 h on agar media in vitro, while urinary samples are usually incubated for 24 h. Consequently, microbiologists should be prompt to prolong the incubation of agar media when the direct examination showed Gram-negative coccobacilli. Oligella is accurately identified using MALDI-TOF mass spectrometry, but biochemical methods often provided inconsistent results. Specific guidelines for antimicrobial susceptibility testing of Oligella lack but the incubation could require up to 48 h of incubation. In contrast to O. urethralis, which is susceptible to third-generation cephalosporin, O. ureolytica is likely resistant to numerous antimicrobials. Genectic determinants of resistance were identified for beta-lactams and aminoglycosides.
CONCLUSION
Oligella is an uncommon pathogen that can be underrecognized. Microbiologists should be prompt to prolong the incubation of agar media plated with urines when the direct examination showed Gram-negative coccobacilli. Carbapenems should probably be given for the empirical treatment.
Topics: Humans; Microbial Sensitivity Tests; Urinary Tract Infections; Anti-Bacterial Agents; Gram-Negative Bacterial Infections
PubMed: 38668878
DOI: 10.1007/s10096-024-04797-9 -
Journal of Cerebral Blood Flow and... Apr 2024Ischaemic stroke results in the formation of a cerebral infarction bordered by an ischaemic penumbra. Characterising the proteins within the ischaemic penumbra may... (Review)
Review
Ischaemic stroke results in the formation of a cerebral infarction bordered by an ischaemic penumbra. Characterising the proteins within the ischaemic penumbra may identify neuro-protective targets and novel circulating markers to improve patient care. This review assessed data from studies using proteomic platforms to compare ischaemic penumbra tissues to controls following experimental stroke in animal models. Proteins reported to differ significantly between penumbra and control tissues were analysed to identify protein-protein interactions and over-represented pathways. Sixteen studies using rat (n = 12), mouse (n = 2) or primate (n = 2) models were included. Heterogeneity in the design of the studies and definition of the penumbra were observed. Analyses showed high abundance of p53 in the penumbra within 24 hours of permanent ischaemic stroke and was implicated in driving apoptosis, cell cycle progression, and ATM- MAPK- and p53- signalling. Between 1 and 7 days after stroke there were changes in the abundance of proteins involved in the complement and coagulation pathways. Favourable recovery 1 month after stroke was associated with an increase in the abundance of proteins involved in wound healing. Poor recovery was associated with increases in prostaglandin signalling. Findings suggest that p53 may be a target for novel therapeutics for ischaemic stroke.
PubMed: 38639008
DOI: 10.1177/0271678X241248502 -
Frontiers in Plant Science 2024Plants from the genus (Aizoaceae) have been traditionally used for millennia by the Khoe and Khoen people in southern Africa, as an appetite suppressant as well as a...
Plants from the genus (Aizoaceae) have been traditionally used for millennia by the Khoe and Khoen people in southern Africa, as an appetite suppressant as well as a mood elevator. In more recent times, this mood-elevating activity has been commercialised in the South African natural products industry for the treatment of anxiety and depression, with several products available both locally and abroad. Research on this species has seen rapid growth with advancements in analytical and pharmacological tools, in an effort to understand the composition and biological activity. The Web of Science (WoS) database was searched for articles related to 'Sceletium' and 'Mesembrine'. These data were additionally analysed by bibliometric software (VOSviewer) to generate term maps and author associations. The thematic areas with the most citations were South African Traditional Medicine for mental health (110) and anxiolytic agents (75). Pioneer studies in the genus focused on chemical structural isolation, purification, and characterisation and techniques such as thin layer chromatography, liquid chromatography (HPLC, UPLC, and more recently, LC-MS), gas chromatography mass spectrometry (GC-MS), and nuclear magnetic resonance (NMR) to study mesembrine alkaloids. Different laboratories have used a diverse range of extraction and preanalytical methods that became routinely favoured in the analysis of the main metabolites (mesembrine, mesembranol, mesembranone, and Sceletium A4) in their respective experimental settings. In contrast with previous reviews, this paper identified gaps in the research field, being a lack of toxicology assays, a deficit of clinical assessments, too few bioavailability studies, and little to no investigation into the minor alkaloid groups found in . Future studies are likely to see innovations in analytical techniques like leaf spray mass spectrometry and direct analysis in real-time ionisation coupled with high-resolution time-of-flight mass spectrometry (DART-HR-TOF-MS) for rapid alkaloid identification and quality control purposes. While has been the primary focus, studying other species may aid in establishing chemotaxonomic relationships and addressing challenges with species misidentification. This research can benefit the nutraceutical industry and conservation efforts for the entire genus. At present, little to no pharmacological information is available in terms of the molecular physiological effects of mesembrine alkaloids in medical clinical settings. Research in these fields is expected to increase due to the growing interest in as a herbal supplement and the potential development of mesembrine alkaloids into pharmaceutical drugs.
PubMed: 38576783
DOI: 10.3389/fpls.2024.1268101