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Metabolomics: Challenges and Opportunities in Systems Biology Studies

Mediani A, Baharum SN

Methods Mol Biol, 2024;2745:77-90.
PMID: 38060180 DOI: 10.1007/978-1-0716-3577-3_5

Metabolomics can provide diagnostic, prognostic, and therapeutic biomarker profiles of individual patients because a large number of metabolites can be simultaneously measured in biological samples in an unbiased manner. Minor stimuli can result in substantial alterations, making it a valuable target for analysis. Due to the complexity and sensitivity of the metabolome, studies must be devised to maintain consistency, minimize subject-to-subject variation, and maximize information recovery. This effort has been aided by technological advances in experimental design, rodent models, and instrumentation. Proton Nuclear Magnetic Resonance (1H-NMR) spectroscopy of biofluids, such as plasma, urine, and faeces provide the opportunity to identify biomarker change patterns that reflect the physiological or pathological status of an individual patient. Metabolomics has the ultimate potential to be useful in a clinical context, where it could be used to predict treatment response and survival and for early disease diagnosis. During drug treatment, an individual's metabolic status could be monitored and used to predict deleterious effects. Therefore, metabolomics has the potential to improve disease diagnosis, treatment, and follow-up care. In this chapter, we demonstrate how a metabolomics study can be used to diagnose a disease by classifying patients as either healthy or pathological, while accounting for individual variation.

Matched MeSH terms: Biomarkers/metabolism
Fulltext Impact of diabetes mellitus on osteoarthritis: a scoping review on biomarkers

Seow SR, Mat S, Ahmad Azam A, Rajab NF, Safinar Ismail I, Singh DKA, et al.

Expert Rev Mol Med, 2024 Apr 12;26:e8.
PMID: 38606593 DOI: 10.1017/erm.2024.7

Osteoarthritis (OA) commonly affects the knee and hip joints and accounts for 19.3% of disability-adjusted life years and years lived with disability worldwide (Refs , ). Early management is important in order to avoid disability uphold quality of life (Ref. ). However, a lack of awareness of subclinical and early symptomatic stages of OA often hampers early management (Ref. ). Moreover, late diagnosis of OA among those with severe disease, at a stage when OA management becomes more complicated is common (Refs , , , ). Established risk factors for the development and progression of OA include increasing age, female, history of trauma and obesity (Ref. ). Recent studies have also drawn a link between OA and metabolic syndrome, which is characterized by insulin resistance, dyslipidaemia and hypertension (Refs , ).

Matched MeSH terms: Biomarkers/metabolism
Fulltext Cellular and molecular changes in orthodontic tooth movement

Zainal Ariffin SH, Yamamoto Z, Zainol Abidin IZ, Megat Abdul Wahab R, Zainal Ariffin Z

ScientificWorldJournal, 2011;11:1788-803.
PMID: 22125437 DOI: 10.1100/2011/761768

Tooth movement induced by orthodontic treatment can cause sequential reactions involving the periodontal tissue and alveolar bone, resulting in the release of numerous substances from the dental tissues and surrounding structures. To better understand the biological processes involved in orthodontic treatment, improve treatment, and reduce adverse side effects, several of these substances have been proposed as biomarkers. Potential biological markers can be collected from different tissue samples, and suitable sampling is important to accurately reflect biological processes. This paper covers the tissue changes that are involved during orthodontic tooth movement such as at compression region (involving osteoblasts), tension region (involving osteoclasts), dental root, and pulp tissues. Besides, the involvement of stem cells and their development towards osteoblasts and osteoclasts during orthodontic treatment have also been explained. Several possible biomarkers representing these biological changes during specific phenomenon, that is, bone remodelling (formation and resorption), inflammation, and root resorption have also been proposed. The knowledge of these biomarkers could be used in accelerating orthodontic treatment.

Matched MeSH terms: Biomarkers/metabolism*
Non-coding RNAs: Emerging biomarkers and therapeutic targets in ulcerative colitis

Kazmi I, Altamimi ASA, Afzal M, Majami AA, Abbasi FA, Almalki WH, et al.

Pathol Res Pract, 2024 Jan;253:155037.
PMID: 38160482 DOI: 10.1016/j.prp.2023.155037

Ulcerative colitis (UC) is a persistent inflammatory condition affecting the colon's mucosal lining, leading to chronic bowel inflammation. Despite extensive research, the precise molecular mechanisms underlying UC pathogenesis remain elusive. NcRNAs form a category of functional RNA molecules devoid of protein-coding capacity. They have recently surfaced as pivotal modulators of gene expression and integral participants in various pathological processes, particularly those related to inflammatory disorders. The diverse classes of ncRNAs, encompassing miRNAs, circRNAs, and lncRNAs, have been implicated in UC. It highlights their involvement in key UC-related processes, such as immune cell activation, epithelial barrier integrity, and the production of pro-inflammatory mediators. ncRNAs have been identified as potential biomarkers for UC diagnosis and monitoring disease progression, offering promising avenues for personalized medicine. This approach may pave the way for novel, more specific treatments with reduced side effects, addressing the current limitations of conventional therapies. A comprehensive understanding of the interplay between ncRNAs and UC will advance our knowledge of the disease, potentially leading to more effective and personalized treatments for patients suffering from this debilitating condition. This review explores the pivotal role of ncRNAs in the context of UC, shedding light on their possible targets for diagnosis, prognosis, and therapeutic interventions.

Matched MeSH terms: Biomarkers/metabolism
NMR metabolomics for evaluating passage number and harvesting effects on mammalian cell metabolome

Abdul-Hamid NA, Abas F, Maulidiani M, Ismail IS, Tham CL, Swarup S, et al.

Anal Biochem, 2019 07 01;576:20-32.
PMID: 30970239 DOI: 10.1016/j.ab.2019.04.001

The variation in the extracellular metabolites of RAW 264.7 cells obtained from different passage numbers (passage 9, 12 and 14) was examined. The impact of different harvesting protocols (trypsinization and scraping) on recovery of intracellular metabolites was then assessed. The similarity and variation in the cell metabolome was investigated using 1H NMR metabolic profiling modeled using multivariate data analysis. The characterization and quantification of metabolites was performed to determine the passage-related and harvesting-dependent effects on impacted metabolic networks. The trypsinized RAW cells from lower passages gave higher intensities of most identified metabolites, including asparagine, serine and tryptophan. Principal component analysis revealed variation between cells from different passages and harvesting methods, as indicated by the formation of clusters in score plot. Analysis of S-plots revealed metabolites that acted as biomarkers in discriminating cells from different passages including acetate, serine, lactate and choline. Meanwhile lactate, glutamine and pyruvate served as biomarkers for differentiating trypsinized and scraped cells. In passage-dependent effects, glycolysis and TCA cycle were influential, whereas glycerophospholipid metabolism was affected by the harvesting method. Overall, it is proposed that typsinized RAW cells from lower passage numbers are more appropriate when conducting experiments related to NMR metabolomics.

Matched MeSH terms: Biomarkers/metabolism
Analysis of CD 133 Expression in Oral Leukoplakia

Tegginamani AS, Kallarakkal TG, Vanishree HS, Muttalib KBA

J Coll Physicians Surg Pak, 2019 Jul;29(7):688.
PMID: 31253228 DOI: 10.29271/jcpsp.2019.07.688
Matched MeSH terms: Biomarkers/metabolism
Recent insights on the significance of transcriptomic and metabolomic analysis of male factor infertility

Lee LK, Foo KY

Clin Biochem, 2014 Jul;47(10-11):973-82.
PMID: 24875852 DOI: 10.1016/j.clinbiochem.2014.05.053

Infertility is a worldwide reproductive health problem which affects approximately 15% of couples, with male factor infertility dominating nearly 50% of the affected population. The nature of the phenomenon is underscored by a complex array of transcriptomic, proteomic and metabolic differences which interact in unknown ways. Many causes of male factor infertility are still defined as idiopathic, and most diagnosis tends to be more descriptive rather than specific. As such, the emergence of novel transcriptomic and metabolomic studies may hold the key to more accurately diagnose and treat male factor infertility. This paper provides the most recent evidence underlying the role of transcriptomic and metabolomic analysis in the management of male infertility. A summary of the current knowledge and new discovery of noninvasive, highly sensitive and specific biomarkers which allow the expansion of this area is outlined.

Matched MeSH terms: Biomarkers/metabolism
Fulltext Identification of AOC3 and LRRC17 as Colonic Fibroblast Activation Markers and Their Potential Roles in Colorectal Cancer Progression

Ahmad Zawawi SS, Mohd Azram NAS, Sulong S, Zakaria AD, Lee YY, Che Jalil NA, et al.

Asian Pac J Cancer Prev, 2023 Sep 01;24(9):3099-3107.
PMID: 37774061 DOI: 10.31557/APJCP.2023.24.9.3099

BACKGROUND: Accumulation of cancer-associated fibroblasts (CAFs) in the tumor stroma is linked to poor prognosis in colorectal cancer (CRC). CAF-cancer cell interplay, facilitated by secretomes including transforming growth factor-beta 1 (TGF-β1), supports fibroblast activation, drives colorectal carcinogenesis, and contributes to CRC aggressive phenotypes. Although widely used, traditional CAF biomarkers are found to have heterogeneous and non-specific expression. Amine oxidase copper containing 3 (AOC3) and leucine-rich repeat-containing 17 (LRRC17) have been reported to be emerging markers of myofibroblasts.
AIM: Our objective was to investigate the potential of AOC3 and LRRC17 as biomarkers for fibroblast activation thus predicting their roles in CRC progression.
METHODS: Immunofluorescence (IF) staining of AOC3 and LRRC17 was performed on myofibroblast line (CCD-112CoN), primary fibroblasts from colorectal tumor (CAFs), and adjacent normal tissue (normal fibroblasts-NFs). SW620 (epithelial CRC cell line) was used as a control. Conventional CAF biomarker (alpha-smooth muscle actin - α-SMA) was included in the IF analysis. Fluorescence intensity was compared between groups using ImageJ software. Proliferation and contractility of treated cells were assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) and collagen gel contraction assays, respectively. Fibroblast contraction under TGF-β1 treatment was compared to those treated with complete medium (addition of 10% serum) and serum free (SF) medium.
RESULTS: Positive AOC3, LRRC17, and α-SMA expression were observed in colonic fibroblasts, more prominent in CAFs, whereas negative staining was found in SW620. Significant downregulation of AOC3, and upregulations in LRRC17 and α-SMA expression was found in TGF-β1-treated fibroblasts compared to SF medium treatment (p-value<0.05). All fibroblasts exhibited higher proliferation in complete medium and under treatment with conditioned medium from SW620 than SF medium. Significant contraction of NFs was recorded in complete medium and TGF-β1 (p-value<0.01).
CONCLUSION: Our results demonstrate AOC3 and LRRC17 as the potential markers of CAF activation which promote CRC progression.

Matched MeSH terms: Biomarkers/metabolism
Harnessing the role of microneedles as sensors: current status and future perspectives

Ravindra Babu M, Vishwas S, Gulati M, Dua K, Kumar Singh S

Drug Discov Today, 2024 Jul;29(7):104030.
PMID: 38762087 DOI: 10.1016/j.drudis.2024.104030

In recent years, microneedles (MNs) have been transformed to serve a wide range of applications in the biomedical field. Their role as sensors in wearable devices has provided an alternative to blood-based monitoring of health and diagnostic methods. Hence, they have become a topic of research interest for several scientists working in the biomedical field. These MNs as sensors offer the continuous monitoring of biomarkers like glucose, nucleic acids, proteins, polysaccharides and electrolyte ions, which can therefore screen for and diagnose disease conditions in humans. The present review focuses on types of MN sensors and their applications. Various clinical trials and bottlenecks of MN R&D are also discussed.

Matched MeSH terms: Biomarkers/metabolism
Fulltext A preliminary finding: immunohistochemical localisation and distribution of placental angiotensin II receptor subtypes in normal and preeclamptic pregnancies

Judson JP, Nadarajah VD, Bong YC, Subramaniam K, Sivalingam N

Med J Malaysia, 2006 Jun;61(2):173-80.
PMID: 16898308

Pre-eclampsia or pregnancy induced hypertension (PIH) affects 6-8% of all pregnancies. Although the underlying mechanism of PIH is still unknown, it is widely believed that the placenta plays an important role. It was thought that an ischemic placenta due to poor perfusion can precipitate the signs and symptoms of PIH. This study aims to investigate the possible role of Type 1(AT1) and Type 2 (AT2) angiotensin II receptor subtypes in the mechanism of PIH. AT1 receptor stimulation causes vasoconstriction and AT2 receptor stimulation causes vasodilatation. Investigating the interactions of these two receptors in the placenta provides an insight as to the balance that may exist between AT1 and AT2 receptors in normal pregnancy. Any disruption to the balance might cause a disruption of the blood flow in the placenta, leading to PIH. Placentas were collected from 11 PIH patients and 11 normal patients. Immunohistochemistry techniques were performed on the placental tissue to determine the distribution of AT1 and AT2 receptors in the placental tissue qualitatively and quantitatively. It was observed that in normal patients, the balance between AT1 and AT2 receptors is that the level of AT2 receptors is higher than the level of AT1 receptors. However in the PIH patient, it was observed that the normal balance was disrupted. In PIH patients the level of AT1 receptors was observed to be higher than the level of AT2 receptors. This study suggests that disruption of the balance between AT1 and AT2 receptors observed in PIH placentas might cause a decrease in blood flow to the placenta, causing it to be poorly perfused. This may cause placental ischemia which may lead to PIH.

Matched MeSH terms: Biomarkers/metabolism
Cell-targeting aptamers act as intracellular delivery vehicles

Gopinath SC, Lakshmipriya T, Chen Y, Arshad MK, Kerishnan JP, Ruslinda AR, et al.

Appl Microbiol Biotechnol, 2016 Aug;100(16):6955-69.
PMID: 27350620 DOI: 10.1007/s00253-016-7686-2

Aptamers are single-stranded nucleic acids or peptides identified from a randomized combinatorial library through specific interaction with the target of interest. Targets can be of any size, from small molecules to whole cells, attesting to the versatility of aptamers for binding a wide range of targets. Aptamers show drug properties that are analogous to antibodies, with high specificity and affinity to their target molecules. Aptamers can penetrate disease-causing microbial and mammalian cells. Generated aptamers that target surface biomarkers act as cell-targeting agents and intracellular delivery vehicles. Within this context, the "cell-internalizing aptamers" are widely investigated via the process of cell uptake with selective binding during in vivo systematic evolution of ligands by exponential enrichment (SELEX) or by cell-internalization SELEX, which targets cell surface antigens to be receptors. These internalizing aptamers are highly preferable for the localization and functional analyses of multiple targets. In this overview, we discuss the ways by which internalizing aptamers are generated and their successful applications. Furthermore, theranostic approaches featuring cell-internalized aptamers are discussed with the purpose of analyzing and diagnosing disease-causing pathogens.

Matched MeSH terms: Biomarkers/metabolism
Association between glycation biomarkers, hyperglycemia, and micronucleus frequency: A meta -analysis

Deo P, Fenech M, Dhillon VS

Mutat Res Rev Mutat Res, 2021 01 29;787:108369.
PMID: 34083054 DOI: 10.1016/j.mrrev.2021.108369

Micronucleus assay has been used as a biomarker of DNA damage, chromosomal instability, cancer risk and accelerated aging. In this review, a meta-analysis was performed to assess the association between micronuclei (MNi) and diseases with increased advanced glycation end products (AGEs) and HbA1c. The review identified eight studies with 632 subjects with disease and 547 controls. The Mean Ratio (MRi) for AGE levels (MRi = 2.92, 95 %CI: 2.06-4.13, P < 0.00001) and HbA1c levels (MRi = 1.32, 95 %CI: 1.12-1.56, P = 0.001) were significantly higher in the disease group compared to healthy controls. The meta-analysis indicated that the overall estimates of MRi for MNi was 1.83 (95 %CI: 1.38-2.42, p < 0.0001) in subjects with disease compared to controls. Significant increases in MRi for MNi were also observed in the following sub-groups: subjects with disease for elevated AGEs (MRi = 1.62, 95 %CI: 1.12-2.35, P = 0.01), elevated HbA1c (MRi = 2.13, 95 %CI: 1.33-3.39, P = 0.002), lymphocytes MNi (MRi = 1.74, 95 %CI: 1.29-2.33, P = 0.0003), exfoliated buccal cells MNi (MRi = 2.86, 95 %CI: 1.19-6.87, P = 0.02), type 2 diabetes mellitus (T2DM) (MRi = 1.99, 95 %CI: 1.17-3.39, P = 0.01), chronic renal disease (MRi = 1.68, 95 %CI: 1.18-2.38, P = 0.004) and other disease groups (MRi = 2.52, 95 %CI: 1.28-4.96, P = 0.008). The results of this review suggest that MNi could be used as a biomarker of DNA damage and chromosomal instability in degenerative disease where increased AGEs and HbA1c are implicated. The lack of heterogeneity for MN frequency when considered either for all studies or subgroup strengthened the MRi of the meta-analysis. However, the lack of significant association between MRi for MNi and MRi for AGEs or HbA1c indicates that the case-control studies investigated may be confounded by other variables. Thus, larger studies with long term AGE exposure is warranted to further understand the role of MN formation in the initiation and progression of diseases caused by excessive glycation.

Matched MeSH terms: Biomarkers/metabolism*
Cytokine Profile in Chronic Periodontitis Patients with and without Obesity: A Systematic Review and Meta-Analysis

Akram Z, Abduljabbar T, Abu Hassan MI, Javed F, Vohra F

Dis Markers, 2016;2016:4801418.
PMID: 27795608

To investigate the cytokine profile as biomarkers in the gingival crevicular fluid (GCF) of chronic periodontitis (CP) patients with and without obesity, MEDLINE/PubMed, EMBASE, ScienceDirect, and SCOPUS databases were combined with handsearching of articles published from 1977 up to May 2016 using relevant MeSH terms. Meta-analyses were conducted separately for each of the cytokines: resistin, adiponectin, TNF-α, leptin, IL-6, IL-8, and IL-1β. Forest plots were produced reporting standardized mean difference of outcomes and 95% confidence intervals. Eleven studies were included. Three studies showed comparable levels of leptin among obese and nonobese patients with CP. Four studies reported comparable levels of interleukin- (IL-) 6 and resistin whereas five studies reported comparable levels of adiponectin. Two studies reported similar levels of CRP in patients with periodontitis with and without obesity. One study showed higher levels of tumor necrosis factor-alpha in obese patients with CP. One study showed higher levels of IL-1β and IL-8 in obese patients with CP. The level of localized periodontal inflammation may have a greater influence on the GCF proinflammatory biomarker levels as compared to systemic obesity. Whether patients having chronic periodontitis with obesity have elevated proinflammatory GCF biomarkers levels compared to nonobese individuals remains debatable.

Matched MeSH terms: Biomarkers/metabolism*
Expression of Odontogenic and Osteogenic Markers in DPSCs and SHED: A Review

Ching HS, Luddin N, Rahman IA, Ponnuraj KT

Curr Stem Cell Res Ther, 2017;12(1):71-79.
PMID: 27527527

The odontogenic and osteogenic potential of dental pulp stem cells (DPSCs) and stem cells from human exfoliated deciduous tooth (SHED) have been shown clearly by various in vitro and in vivo studies. The findings are promising and demonstrated that dental tissue engineering can give a new hope to the individuals suffering from tooth loss and dental diseases. The evaluation of odontogenic and osteogenic differentiation of DPSCs and SHED is commonly carried out by an illustration of the expression of varied related markers. In this review, few commonly used markers such as alkaline phosphatase (ALP), collagen type 1 (Col I), dentin matrix acid phosphoprotein 1 (DMP1), dentin sialophosphoprotein (DSPP), matrix extracellular phosphoglycoprotein (MEPE), osteocalcin (OCN), and osteopontin (OPN). DSPP, DMP1, and MEPE (odontogenic markers), which play an important role during early odontoblastic differentiation and late dentin mineralization, have been highlighted. Osteoblastic proliferation and early/late osteoblastic differentiation can be assessed by estimating the expression of Col I, ALP, OCN and OPN. Despite that, till date, there is no marker which could demonstrate for certain, the differentiation of human DPSCs and SHED towards the odontogenic and osteogenic lineage. This review suggests that SHED are noticeably different from DPSCs and exhibited higher capacity for osteogenic differentiation compared to DPSCs. On the other hand, different expression levels are shown by SHED and DPSCs with regards to the osteoblast markers for osteoblastic differentiation, where, SHED expressed higher levels of ALP, Col I and OCN compared to DPSCs.

Matched MeSH terms: Biomarkers/metabolism*
Aliphatic hydrocarbons and triterpane biomarkers in mangrove oyster (Crassostrea belcheri) from the west coast of Peninsular Malaysia

Vaezzadeh V, Zakaria MP, Bong CW

Mar Pollut Bull, 2017 Nov 15;124(1):33-42.
PMID: 28693809 DOI: 10.1016/j.marpolbul.2017.07.008

The Straits of Malacca is one of the world's busiest shipping routes where frequent oil spills occur. Rapid development in the west coast of Peninsular Malaysia is the other major source of petroleum pollution in this narrow waterway. In order to identify occurrence and origin of hydrocarbons in the Straits, mangrove oysters (Crassostrea belcheri) were collected from five sampling locations and analysed for n-alkanes and biomarkers. Soxhlet apparatus and two step column chromatography were used for extraction, purification and fractionation of the oysters. Petroleum origin n-alkanes were detected in majority of the sampling locations which is indicative of anthropogenic activities in this region. Using source and maturity diagnostic ratios for hopanes revealed used crankcase oil as the main source of petroleum hydrocarbons in oysters from all sampling locations except for the Pulau Merambong where signature of South East Asia crude oil (SEACO) was detected.

Matched MeSH terms: Biomarkers/metabolism
Alterations of serum and saliva oxidative markers in patients with bronchial asthma

Abboud MM, Al-Rawashde FA, Al-Zayadneh EM

J Asthma, 2022 Nov;59(11):2154-2161.
PMID: 34855555 DOI: 10.1080/02770903.2021.2008426

BACKGROUNDS: The development of asthma is highly affected by exposure to exogenous and endogenous oxidative molecules, but the impact of this exposure on the pathophysiology of asthma has received little attention.
OBJECTIVES: Evaluating group of selective oxidative stress markers as a tool in the management of asthma disease.
METHODS: In comparison with matched healthy controls, levels of the oxidant and antioxidant markers: lipid peroxidation malondialdehyde (MDA), Total glutathione (tGSH), Uric acid (UA), Glutathione peroxidase (GPx), Catalase (CAT) superoxide dismutase (SOD), and Total antioxidant capacity (TAC) were assessed in serum and saliva of different asthma groups.
RESULTS: All oxidative markers in serum and saliva of asthma patients showed significant alterations from normal healthy controls (P 0.05).
CONCLUSION: Determination of the oxidative markers GPx, CAT, UA in serum or saliva can distinguish asthma from healthy states. The serum levels of UA and TAC are highly effective in monitoring asthma severity, while the salivary GPx, CAT, UA, MDA are beneficial in the management of childhood asthma. Discrimination of the age factor between asthma groups can be achieved by testing GPx, SOD, TAC in serum.

Matched MeSH terms: Biomarkers/metabolism
Effect of diisobutyl adipate on the expression of biomarker genes that respond to endocrine disruption and on gonadal sexual differentiation in Japanese medaka (Oryzias latipes)

Horie Y, Chihaya Y, Yap CK, Ríos JM, Ramaswamy BR, Uaciquete D

Comp Biochem Physiol C Toxicol Pharmacol, 2024 Mar;277:109836.
PMID: 38218565 DOI: 10.1016/j.cbpc.2024.109836

Phthalate and non-phthalate plasticizers are used in polymer materials, such as plastic and rubber. It has recently been found that diisobutyl adipate (DIBA), which is considered an environmentally safe non-phthalate plasticizer, potentially acts as a thyroid disruptor in fish. Here, we investigated the sexual hormone effects of DIBA based on the expression levels of genes that respond to endocrine disruption and sexual hormone activity in the livers and gonads, and on gonadal sexual differentiation in Japanese medaka. Compared with the control group, the mRNA expression of chgH, vtg1, vtg2, and esr1 was significantly suppressed in the livers of DIBA exposed XX individuals. Furthermore, the mRNA expression of gsdf was significantly upregulated and downregulated in the gonads of XX and XY individuals, respectively. The mRNA expressions of esr1 and esr2b were significantly suppressed by DIBA exposure in the gonads of both XX and XY individuals. These observations suggest that DIBA has potential androgenic activity in Japanese medaka. However, normal testes and ovaries were observed in respective XY and XX medaka after DIBA exposure; therefore, these results suggest that DIBA may have weak androgenic activity.

Matched MeSH terms: Biomarkers/metabolism
Fulltext Exploring the Neuroinflammatory Pathway in Epilepsy and Cognitive Impairment: Role of HMGB1 and Translational Challenges

Ngadimon IW, Seth EA, Shaikh MF

Front Biosci (Landmark Ed), 2024 Jun 24;29(6):229.
PMID: 38940048 DOI: 10.31083/j.fbl2906229

Neuroinflammation has emerged as a shared molecular mechanism in epilepsy and cognitive impairment, offering new insights into the complex interplay between immune responses and brain function. Evidence reveals involvement of High mobility group box 1 (HMGB1) in blood-brain barrier disruption and correlations with epilepsy severity and drug resistance. While anti-inflammatory treatments show promise, translating these discoveries faces challenges in elucidating mechanisms and developing reliable biomarkers. However, strategically targeting neuroinflammation and HMGB1-mediated inflammation holds therapeutic potential. This review synthesises knowledge on HMGB1 and related biomarkers in epilepsy and cognitive impairment to shape future research and treatments targeting these intricate inflammatory processes.

Matched MeSH terms: Biomarkers/metabolism
Fulltext The relationship between hair cortisol concentration and autism diagnosis

Lin PI, John JR, Masi A, Ong LK, Mathew NE, Moni MA, et al.

J Psychiatr Res, 2024 Aug;176:68-76.
PMID: 38850580 DOI: 10.1016/j.jpsychires.2024.05.052

BACKGROUND: Autistic children are prone to experience heightened levels of distress and physiological reactivity to a range of sensory, social, and emotional stimuli. In line with this, multiple studies have demonstrated that autistic children have higher acute cortisol stress responses to adverse or threatening stimuli and altered cortisol awakening responses. However, few studies have examined whether this sensitivity may relate to heightened levels of chronic stress and persistently elevated hypothalamic-pituitary-adrenal (HPA) axis activity. The measurement of cortisol accumulation in hair is considered a non-invasive biomarker of chronic stress and has been associated with several childhood diseases. Here, we investigated whether hair cortisol concentration in a large sample of autistic children differed from non-autistic children, and after accounting for a range of child, parental and family-level characteristics.
METHODS: Hair cortisol concentration was measured in 307 autistic children and 282 non-autistic controls aged between 2 and 17 years recruited from four Australian states who participated in providing hair samples and demographic data to the Australian Autism Biobank. Independent samples t-test or one-way analysis of variance (ANOVA) were conducted to determine significant differences in the mean hair cortisol concentration (pg/mg) between potential covariates. Primary analysis included multivariable regression modelling of the collapsed sample to identify variables that were significantly associated with hair cortisol concentration after controlling for covariates. We also accounted for the potential interaction of multiple biological (e.g., age, sex, BMI) and psychosocial characteristics at the level of the child, the mother and the father, and the family unit.
RESULTS: Our findings suggest that the diagnosis of autism was not a significant predictor of chronic stress, as measured by hair cortisol concentration. However, findings of the multivariable regression analysis showed that key factors such as area of residence (Queensland vs Victorian state of residence) and decrease in child's age were significantly associated with higher hair cortisol concentration whereas lower family income was significantly associated with higher hair cortisol concentration.
CONCLUSION: To our knowledge, this is the first study to show that socioeconomic factors such as family annual income affect hair cortisol status in autistic children, indicating that the psychosocial environment may be a potential mediator for chronic stress in autistic children just as it has been demonstrated in non-autistic children.

Matched MeSH terms: Biomarkers/metabolism
Role of fish oil in human health and possible mechanism to reduce the inflammation

Ellulu MS, Khaza'ai H, Abed Y, Rahmat A, Ismail P, Ranneh Y

Inflammopharmacology, 2015 Jun;23(2-3):79-89.
PMID: 25676565 DOI: 10.1007/s10787-015-0228-1

The roles of Omega-3 FAs are inflammation antagonists, while Omega-6 FAs are precursors for inflammation. The plant form of Omega-3 FAs is the short-chain α-linolenic acid, and the marine forms are the long-chain fatty acids: docosahexaenoic acid and eicosapentaenoic acid. Omega-3 FAs have unlimited usages, and they are considered as omnipotent since they may benefit heart health, improve brain function, reduce cancer risks and improve people's moods. Omega-3 FAs also have several important biological effects on a range of cellular functions that may decrease the onset of heart diseases and reduce mortality among patients with coronary heart disease, possibly by stabilizing the heart's rhythm and by reducing blood clotting. Some review studies have described the beneficial roles of Omega-3 FAs in cardiovascular diseases (CVDs), cancer, diabetes, and other conditions, including inflammation. Studies of the effect of Omega-3 FAs gathered from studies in diseased and healthy population. CVDs including atherosclerosis, coronary heart diseases, hypertension, and metabolic syndrome were the major fields of investigation. In studies of obesity, as the central obesity increased, the level of adipocyte synthesis of pro-inflammatory cytokines like tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) were increased and the level of anti-inflammatory adiponectin was decreased indicating a state of inflammation. The level of C reactive protein (CRP) synthesized from hepatocyte is increased by the influence of IL-6. CRP can be considered as a marker of systemic inflammation associated with increased risks of CVDs. In molecular studies, Omega-3 FAs have direct effects on reducing the inflammatory state by reducing IL-6, TNF-α, CRP and many other factors. While the appropriate dosage along with the administrative duration is not known, the scientific evidence-based recommendations for daily intake are not modified.

Matched MeSH terms: Biomarkers/metabolism

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