Biological Markers Of Disease Research Articles

Biofunctionalization-optimized MoS2-based FET biosensors for the detection of Tau protein

Field effect transistor (FET)-based biosensors can accurately quantify changes in weak signals and show excellent performance advantages in the detection of trace biological disease markers. Biological functionalization (biofunctionalization) is an important factor in the fabrication of FET-based biosensors, which directly affects the performance of the biosensor. However, little attention from researchers has been paid to biofunctionalization, which results in uneven performance of biosensors. Herein, MoS2-based FET biosensors are designed and fabricated using four different biofunctionalization methods. The most suitable biofunctionalization method is obtained by comparing the sensing performances of different functionalized MoS2-based FET biosensors. Moreover, the working mechanism of the optimized biofunctionalization method is explored. Besides, the biofunctionalization-optimized MoS2-based FET biosensor exhibits excellent sensing performance, achieving sensitive detection of Tau protein in the concentration range of 10−2–103 pg/mL. This study provides a universal and effective strategy for the biofunctionalization optimization of two-dimensional materials-based FET biosensors.

An introduction to environmental neurotoxicology: Lessons from a clinical perspective

In 1992, the Committee on Neurotoxicology and Models for Assessing Risk of the National Academy of Sciences in Washington DC focused with a scientific perspective on the identification of substances with neurotoxic potential, studies of exposed populations, risk assessment, and biologic markers of disease. This Committee recommended: “all physicians should be trained to take a thorough occupational-exposure history and to be aware of other possible sources of toxic exposure”. Although convened after several outbreaks of neurotoxic syndromes, clinical neurological considerations were lacking. After defining keys words, namely Environment, Neurotoxicology and Neurotoxicants, we present some demonstrative cases; e.g., the Epidemic Neuropathy in Cuba, Minamata disease, ALS/PDC on Guam, and the ALS hot spot in the French Alps. Always with a clinical and practical approach, we will then review the milieux that contain and convey potential neurotoxicants, the different exposure routes and the clinical presentations. Drawing lessons from clinical cases, we offer some thoughts concerning the future of Environmental Neurotoxicology (ENT). Pointing notably to the diffuse chemical contamination of ecosystems and living beings, including Homo sapiens, we question the real impact of agents with neurotoxic potential on the human brain, considering the effects, for example, of air pollution, endocrine disruptors and nanoparticles. Concern is expressed over the lack of knowledge of the non-monotonic kinetics of many of these chemicals, the major concern being related to mixtures and low-dose exposures, as well as the delayed appearance in clinical expression of prevalent neurodegenerative diseases.

Biological markers of Alzheimer's disease in cerebrospinal fluid: clinical and laboratory comparisons

Biological markers of Alzheimer's disease in cerebrospinal fluid: clinical and laboratory comparisons

Different aspects of failing to recover from proactive semantic interference predicts rate of progression from amnestic mild cognitive impairment to dementia.

This study investigated the role of proactive semantic interference (frPSI) in predicting the progression of amnestic Mild Cognitive Impairment (aMCI) to dementia, taking into account various cognitive and biological factors. The research involved 89 older adults with aMCI who underwent baseline assessments, including amyloid PET and MRI scans, and were followed longitudinally over a period ranging from 12 to 55 months (average 26.05 months). The findings revealed that more than 30% of the participants diagnosed with aMCI progressed to dementia during the observation period. Using Cox Proportional Hazards modeling and adjusting for demographic factors, global cognitive function, hippocampal volume, and amyloid positivity, two distinct aspects of frPSI were identified as significant predictors of a faster decline to dementia. These aspects were fewer correct responses on a frPSI trial and a higher number of semantic intrusion errors on the same trial, with 29.5% and 31.6 % increases in the likelihood of more rapid progression to dementia, respectively. These findings after adjustment for demographic and biological markers of Alzheimer's Disease, suggest that assessing frPSI may offer valuable insights into the risk of dementia progression in individuals with aMCI.

Functional ultrasound reveals effects of MRI acoustic noise on brain function

Loud acoustic noise from the scanner during functional magnetic resonance imaging (fMRI) can affect functional connectivity (FC) observed in the resting state, but the exact effect of the MRI acoustic noise on resting state FC is not well understood. Functional ultrasound (fUS) is a neuroimaging method that visualizes brain activity based on relative cerebral blood volume (rCBV), a similar neurovascular coupling response to that measured by fMRI, but without the audible acoustic noise. In this study, we investigated the effects of different acoustic noise levels (silent, 80 dB, and 110 dB) on FC by measuring resting state fUS (rsfUS) in awake mice in an environment similar to fMRI measurement. Then, we compared the results to those of resting state fMRI (rsfMRI) conducted using an 11.7 Tesla scanner. RsfUS experiments revealed a significant reduction in FC between the retrosplenial dysgranular and auditory cortexes (0.56 ± 0.07 at silence vs 0.05 ± 0.05 at 110 dB, p=.01) and a significant increase in FC anticorrelation between the infralimbic and motor cortexes (−0.21 ± 0.08 at silence vs −0.47 ± 0.04 at 110 dB, p=.017) as acoustic noise increased from silence to 80 dB and 110 dB, with increased consistency of FC patterns between rsfUS and rsfMRI being found with the louder noise conditions. Event-related auditory stimulation experiments using fUS showed strong positive rCBV changes (16.5% ± 2.9% at 110 dB) in the auditory cortex, and negative rCBV changes (−6.7% ± 0.8% at 110 dB) in the motor cortex, both being constituents of the brain network that was altered by the presence of acoustic noise in the resting state experiments. Anticorrelation between constituent brain regions of the default mode network (such as the infralimbic cortex) and those of task-positive sensorimotor networks (such as the motor cortex) is known to be an important feature of brain network antagonism, and has been studied as a biological marker of brain disfunction and disease. This study suggests that attention should be paid to the acoustic noise level when using rsfMRI to evaluate the anticorrelation between the default mode network and task-positive sensorimotor network.

First Observations of a Potential Association Between Accumulation of Per- and Polyfluoroalkyl Substances in the Central Nervous System and Markers of Alzheimer's Disease.

The entire human population is exposed to persistent organic pollutants throughout their lives. Among them, per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals widely used in industrial and consumer products that are known to exert adverse effects on human health. As they bioaccumulate in the human brain and are known to be neurotoxic in experimental models, they are assumed to be involved in neurodegenerative processes. In this proof-of-concept study, we measured the level of 18 PFAS in cerebrospinal fluid (CSF) from 8 patients hospitalized with suspected normal pressure hydrocephalus. We then analyzed whether PFAS levels could be related to both biological and clinical markers of Alzheimer's disease. We showed that PFAS and perfluorooctanesulfonate were found in all CSF samples from a French region without fluorochemical industries. Moreover, we observed a significant difference between the levels of PFAS and perfluorooctanesulfonate in the CSF of patients with both Alzheimer's disease markers and cognitive impairment compared with those with only 1 or neither. Two previous studies have shown that PFAS levels in human CSF increase with age and are linked to impaired blood-brain barrier integrity. Our results provide the first evidence of a link between PFAS accumulation in the central nervous system and clinical and biological markers of Alzheimer's disease.

Signaling metabolite β-aminoisobutyric acid as a metabolic regulator, biomarker, and potential exercise pill.

Signaling metabolites can effectively regulate the biological functions of many tissues and organs. β-Aminoisobutyric acid (BAIBA), a product of valine and thymine catabolism in skeletal muscle, has been reported to participate in the regulation of lipid, glucose, and bone metabolism, as well as in inflammation and oxidative stress. BAIBA is produced during exercise and is involved in the exercise response. No side effect has been observed in human and rat studies, suggesting that BAIBA can be developed as a pill that confers the benefits of exercise to subjects who, for some reason, are unable to do so. Further, BAIBA has been confirmed to participate in the diagnosis and prevention of diseases as an important biological marker of disease. The current review aimed to discuss the roles of BAIBA in multiple physiological processes and the possible pathways of its action, and assess the progress toward the development of BAIBA as an exercise mimic and biomarker with relevance to multiple disease states, in order to provide new ideas and strategies for basic research and disease prevention in related fields.

Special Report: Bipolar Disorder II—Frequently Neglected, Misdiagnosed

Special Report: Bipolar Disorder II—Frequently Neglected, Misdiagnosed

Multi-Responsive Sensor Based on Porous Hydrogen-Bonded Organic Frameworks for Selective Sensing of Ions and Dopamine Molecules.

Hydrogen-bonded organic frameworks (HOFs), as an emerging porous material, have attracted increasing research interest in fluorescence sensing due to their inherent fluorescence emission units with unique physicochemical properties. Herein, based on the organic building block 3,3',5,5'-tetrakis-(4-carboxyphenyl)-1,1'-biphenyl (H4TCBP), the porous material HOF-TCBP was successfully synthesized using hydrogen bond self-assembly in a DMF solution. The fluorescence properties of the HOF-TCBP solution showed that when the concentration was high, excimers were easily formed, the PL emission was red-shifted, and the fluorescence intensity became weaker. HOF-TCBP showed good sensitivity and selectivity to metal ions Fe3+, Cr3+, and anion Cr2O72-. In addition, HOF-TCBP can serve as a label-free fluorescent sensor material for the sensitive and selective detection of dopamine (DA). HOF-based DA sensing is actually easy, low-cost, simple to operate, and highly selective for many potential interfering substances, and it has been successfully applied to the detection of DA in biological samples with satisfactory recoveries (101.1-104.9%). To our knowledge, this is the first report of HOF materials for efficient detection of the neurotransmitter dopamine in biological fluids. In short, this work widely broadens the application of HOF materials as fluorescent sensors for the sensing of ions and biological disease markers.

A novel approach for fibrous dysplasia assessment using combined planar and quantitative SPECT/CT analysis of Tc-99m-diphosphonate bone scan in correlation with biological bone turnover markers of disease activity.

To investigate the emerging role of Tc-99m-labeled diphosphonate (Tc-99m-DPD) uptake quantification by SPECT/CT in fibrous dysplasia (FD) bone lesions and its correlation with biological bone turnover markers (BTMs) of disease activity. Seven patients (49 ± 16 years) with a confirmed diagnosis of FD were included in this retrospective study. Bone scans with Tc-99m-DPD and quantitative SPECT/CT (xSPECT/CT) were performed. SUVmax (maximum standard unit value) and SUVmean (mean standard unit value) were measured in all FD bone lesions. The skeletal burden score (SBS) was assessed on planar scintigraphy and multiplied by mean SUV max and SUVmean to generate two new parameters, SBS_SUVmax and SBS_SUVmean, respectively. Planar and xSPECT/CT quantitative measures were correlated with biological BTMs of disease activity, including fibroblast growth factor 23 (FGF-23), alkaline phosphatase (ALP), procollagen 1 intact N-terminal propeptide (P1NP) and C-terminal telopeptide (CTX), as well as scoliosis angle measured on radiographs. Statistical significance was evaluated with Spearman's correlations. A total of 76 FD bone lesions were analyzed, showing an average SUVmax and SUVmean (g/mL) of 13 ± 7.3 and 8 ± 4.5, respectively. SBS, SBS_SUVmax and SBS_SUVmean values were 30.8 ± 25.6, 358 ± 267 and 220.1 ± 164.5, respectively. Mean measured values of FGF-23 (pg/mL), ALP (U/L), P1NP (μg/L) and CTX (pg/mL) were 98.4 (22-175), 283.5 (46-735), 283.1 (31-1,161) and 494 (360-609), respectively. Mean scoliosis angle was 15.7 (7-22) degrees. We found a very strong positive correlation between planar-derived SBS and CTX (r = 0.96, p = 0.010), but no significant correlation between SUVmax or SUVmean and biological BTMs. SBS_SUVmax showed a strong to very strong positive correlation with CTX (ρ = 0.99, p = 0.002), FGF-23 (ρ = 0.91, p = 0.010), ALP (ρ = 0.82, p = 0.020), and P1NP (ρ = 0.78, p = 0.039), respectively. This study showed that biological BTMs are significantly correlated with diphosphonate uptake on bone scan, quantified by a new parameter combining information from both planar and quantitative SPECT/CT. Further analysis of bone scan quantitative SPECT/CT data in a larger patient population might help better characterize the skeletal disease burden in FD, and guide treatment and follow-up.

The cognitive performance in the Phototest is predictor ofbiological markers of Alzheimer's disease.

The abnormal cerebrospinal fluid levels of biomarkers, such as β-amyloid and phosphorylated tau (pTau), support the biological diagnosis of Alzheimer Disease (AD) independently of its clinical stage. However, this invasive exam cannot be extensively applied and requires previous sound clinical screen that can be based on brief, well validated cognitive tests, such as the Phototest. To evaluate the association of partial (naming [NA], total recall [TR], free recall [FR], and verbal fluency) and total scores of the Phototest with the biological diagnosis of AD and the potential use of this test as a screening tool in the clinical work up. Retrospective study of Individuals attending a Memory Clinic who were applied the Phototest and classified, according to cerebrospinal fluid biomarkers (β-amyloid1-42 and pTau), in the biological AD continuum stage (ContAD) as "no AD" (A-), "AD changes" (A+T-) or "AD" (A+T+). Multivariate analyses were conducted with one fixed factor, ContAD, and partial and total Phototest scores. The area under the receiver operating characteristics curve (AUC) was calculated to estimate the capacity of Phototest scores to predict amyloidosis (A+) and AD. The study included 170 individuals (92 A-, 23 A+T- and 55 A+T+). FR (7.9, 0.01 [F,p]) and TR (8.1, 0.001) scores were associated with ContAD and had a moderate ability (AUC 0.71-0.74) to detect the presence of "A+" or "AD". Partial memory scores of Phototest are associated with ContAD. They predict acceptably the presence of abnormal levels of β-amyloid and AD signature in CSF and can be useful to support further biological diagnostic tests.

Noninvasive Testing and Surrogate Markers in Invasive Fungal Diseases.

Invasive fungal infections continue to increase as at-risk populations expand. The high associated morbidity and mortality with fungal diseases mandate the continued investigation of novel antifungal agents and diagnostic strategies that include surrogate biomarkers. Biologic markers of disease are useful prognostic indicators during clinical care, and their use in place of traditional survival end points may allow for more rapid conduct of clinical trials requiring fewer participants, decreased trial expense, and limited need for long-term follow-up. A number of fungal biomarkers have been developed and extensively evaluated in prospective clinical trials and small series. We examine the evidence for these surrogate biomarkers in this review and provide recommendations for clinicians and regulatory authorities.

A Systematic Review of Asthma Readmission Risk Factors

A Systematic Review of Asthma Readmission Risk Factors

Bone damage after chemotherapy for lymphoma: a real-world experience

BackgroundDespite recent improvements in survival due to advances in treatment, the quality of life of patients with lymphoma may be compromised by the long-term complications of chemotherapy and steroid therapy. Among these, a potentially relevant problem is bone loss and the development of fragility fractures.AimTo provide further evidence of clinical or subclinical skeletal complications in correlation with biological variables and markers of bone disease in patients with complete response to therapy.MethodA cross-sectional observational study was conducted on subjects diagnosed with lymphoma with subsequent antineoplastic treatment, disease status after therapy defined as complete response disease for at least a year now. We performed: blood chemistry tests, imaging techniques and screening tools for the assessment of functional status and quality of life (SARC-F and mini-Osteoporosis Quality of Life).ResultsApproximately 50% of patients had osteoporosis, with a prevalence of vertebral fractures of 65.5%. In most patients, we found hypovitaminosis D and high levels of parathyroid hormone (PTH). Furthermore, a statistically significant association was observed between high PTH levels and previous lymphoma treatment. Finally, the Mini-Osteoporosis Quality of life (mini-OQLQ) questionnaire demonstrated a loss of quality of life as a consequence of the change in bone status.ConclusionsPatient treatment design for personalized chemotherapy would be desirable to reduce late effects on bone. Also, early prevention programs need to be applied before starting treatment. The most benefited subpopulations could be not only elderly but also young patients.

Circulating Ceramides- Are Origins Important for Sphingolipid Biomarkers and Treatments?

Biomarkers are important tools for describing the adequacy or inadequacy of biological processes (to allow for the early and accurate diagnosis) and monitoring the biological effects of intervention strategies (to identify and develop optimal dose and treatment strategies). A number of lipid biomarkers are implicated in metabolic disease and the circulating levels of these biomarkers are used in clinical settings to predict and monitor disease severity. There is convincing evidence that specific circulating ceramide species can be used as biological predictors and markers of cardiovascular disease, atherosclerosis and type 2 diabetes mellitus. Here, we review the existing literature that investigated sphingolipids as biomarkers for metabolic disease prediction. What are the advantages and disadvantages? Are circulating ceramides predominantly produced in the liver? Will hepatic sphingolipid inhibitors be able to completely prevent and treat metabolic disease? As sphingolipids are being employed as biomarkers and potential metabolic disease treatments, we explore what is currently known and what still needs to be discovered.

Acute Physiological Effects of Continuous Versus Intermittent Walking During Golf in Individuals With Knee Osteoarthritis: A Pilot Study.

The aim of the study was to compare the acute effects of walking the golf course versus using a golf cart during a round of golf on biological markers of joint disease, joint pain, and cardiovascular parameters in individuals with knee osteoarthritis. Participants with knee OA (n = 10) older than 50 yrs were recruited for this crossover designed study in which they completed two 18-hole rounds of golf: (1) walking the course and (2) using a golf cart. Five control participants (n = 5) performed the walking condition only. Step count, heart rate, rating of perceived exertion and pain using the Numeric Pain Rating Scale were measured during the round. Serum was collected at baseline, 9th hole (halfway), and 18th hole (completion) and tested for biomarkers associated with tissue turnover (cartilage oligomeric matrix protein), inflammation (tumor necrosis factor α, interleukin 1β, interleukin 6), and degradative enzyme production (matrix metalloproteinase 3, matrix metalloproteinase 13). In knee OA participants, walking the course was associated with significantly higher step count and duration of moderate/vigorous physical activity (72.2% vs. 32.6% of the round) but did lead to a significant increase in knee joint pain (P < 0.05). Both conditions caused cartilage oligomeric matrix protein and matrix metalloproteinase 13 concentration increases from baseline to completion (P < 0.05), but inflammatory markers (tumor necrosis factor α, interleukin 6, and interleukin 1β, P < 0.05) only increased when walking the course. Biomarker concentrations did not increase in control participants. Walking the course optimizes the duration of moderate/vigorous activity during a round of golf, but the golf cart is a beneficial option in those with exacerbated joint pain and inflammation that would otherwise limit participation.

MiR-20a-5p Regulates MPP+-Induced Oxidative Stress and Neuroinflammation in HT22 Cells by Targeting IRF9/NF-κB Axis.

Substantial evidence indicates that microRNAs (miRNAs) can be used as biological markers of Parkinson's disease (PD) and contribute to the risk assessment, early diagnosis, and treatment. We aimed to explore the role and potential mechanism of miR-20a-5p on inflammation and oxidative stress in 1-methyl-4-phenyl pyridine ion- (MPP+-) induced HT22 cells. HT22 cells were pretreated with miR-20a-5p mimic and/or pcDNA-IRF9 for 24 h and then treated with MPP+ (0.5 mM) for 24 h. The cell viability and apoptosis were determined using the Cell Counting Kit-8 (CCK-8) and Annexin V FITC/PI staining flow cytometry assay, respectively. The expression and secretion of inflammatory factors and oxidative stress-related factors were detected by enzyme-linked immunosorbent assay (ELISA). The protein expression levels were detected using Western blot analysis. Here, we discovered that MPP+ led to mitochondrial dysfunction, inflammation, and cell damage of HT22 cells, which were alleviated by miR-20a-5p overexpression. We further clarified that interferon regulatory factor 9 (IRF9) was a target gene of miR-20a-5p. IRF9 contributed to MPP+-induced mitochondrial disruption, inflammation, and cell apoptosis. Moreover, IRF9 hindered the improvement of miR-20a-5p overexpression on MPP+-induced neurotoxicity. Furthermore, the decrease of p-P65 level induced by miR-20a-5p mimic was significantly reversed by IRF9 overexpression. These findings demonstrate that miR-20a-5p contributes to MPP+-induced mitochondrial disruption and cell damage, and miR-20a-5p might be a novel therapeutic target for PD.

Біологічна діагностика запальних захворювань кишечника: поточні ідеї і майбутні досягнення

Article presents review of new biological methods for the diagnosis of IBD. The problem of late diagnosis of IBD remains relevant because of increased frequency of adverse consequences of the disease by increasing the length of the period when patients do not receive adequate treatment. Well-known today are biological markers of inflammatory bowel disease, which are determined by non-invasive methods and are often an alternative to colonoscopy. C-reactive protein (CRP) is recognized as one of the most important proteins in the acute inflammation phase. Changes in the content of fecal calprotectin (FCP) in patients with IBD due to the clinical activity of inflammatory bowel disease and are closely related to the extent of colon damage. New fecal biomarkers such as Defensin, Myeloperoxidase, Pyruvate kinase, Lipocalin and others are a sensitive tool for screening for inflammation of the intestine and an indicator of its severity. New fecal markers may help improve the diagnosis, evaluation, and clinical outcomes of treatment of patients with inflammatory bowel disease.

The spectrum of mitochondrial DNA (mtDNA) mutations in pediatric CNS tumors.

BackgroundWe previously established the landscape of mitochondrial DNA (mtDNA) mutations in 23 subtypes of pediatric malignancies, characterized mtDNA mutation profiles among these subtypes, and provided statistically significant evidence for a contributory role of mtDNA mutations to pediatric malignancies.MethodsTo further delineate the spectrum of mtDNA mutations in pediatric central nervous system (CNS) tumors, we analyzed 545 tumor-normal paired whole-genome sequencing datasets from the Children’s Brain Tumor Tissue Consortium.ResultsGermline mtDNA variants were used to determine the haplogroup, and maternal ancestry, which was not significantly different among tumor types. Among 166 (30.5%) tumors we detected 220 somatic mtDNA mutations, primarily missense mutations (36.8%), as well as 22 loss-of-function mutations. Different pediatric CNS tumor subtypes had distinct mtDNA mutation profiles. The number of mtDNA mutations per tumor ranged from 0.20 (dysembryoplastic neuroepithelial tumor [DNET]) to 0.75 (meningiomas). The average heteroplasmy was 10.7%, ranging from 4.6% in atypical teratoid/rhabdoid tumor (AT/RT) to 26% in diffuse intrinsic pontine glioma. High-grade gliomas had a significant higher number of mtDNA mutations per sample than low-grade gliomas (0.6 vs 0.27) (P = .004), with almost twice as many missense mtDNA mutations per sample (0.24 vs 0.11), and higher average heteroplasmy levels (16% vs 10%). Recurrent mtDNA mutations may represent hotspots which may serve as biologic markers of disease.ConclusionsOur findings demonstrate varying contributions of mtDNA mutations in different subtypes of CNS tumors. Sequencing the mtDNA genome may ultimately be used to characterize CNS tumors at diagnosis and monitor disease progression.

Addressing Inaccurate Nosology in Mental Health: A Multilabel Data Cleansing Approach for Detecting Label Noise From Structural Magnetic Resonance Imaging Data in Mood and Psychosis Disorders

BackgroundMental health diagnostic approaches are seeking to identify biological markers to work alongside advanced machine learning approaches. It is difficult to identify a biological marker of disease when the traditional diagnostic labels themselves are not necessarily valid. MethodsWe worked with T1 structural magnetic resonance imaging data collected from 1493 individuals comprising healthy control subjects, patients with psychosis, and their unaffected first-degree relatives. Specifically, the dataset included 176 bipolar disorder probands, 134 schizoaffective disorder probands, 240 schizophrenia probands, 362 control subjects, and 581 patient relatives. We assumed that there might be noise in the diagnostic labeling process. We detected label noise by classifying the data multiple times using a support vector machine classifier, and then we flagged those individuals in which all classifiers unanimously mislabeled those subjects. Next, we assigned a new diagnostic label to these individuals, based on the biological data (magnetic resonance imaging), using an iterative data cleansing approach. ResultsSimulation results showed that our method was highly accurate in identifying label noise. Both diagnostic and biotype categories showed about 65% and 63% of noisy labels, respectively, with the largest amount of relabeling occurring between the healthy control subjects and individuals with bipolar disorder and schizophrenia as well as in unaffected close relatives. The extraction of imaging features highlighted regional brain changes associated with each group. ConclusionsThis approach represents an initial step toward developing strategies that need not assume that existing mental health diagnostic categories are always valid but rather allows us to leverage this information while also acknowledging that there are misassignments.