Levels Of Biomarkers Research Articles

Molecular and immunohistochemical alterations in fluoride-induced neurological impediment in adult rats

SummaryThis study highlights the potential neurotoxic and impaired behavioral effects associated with high fluoride concentrations in drinking water. PurposeFluoride is known to cause neurotoxicity, evinced by lower I.Q. levels in children from high-fluoride regions as compared to those in low-fluoride regions. Thus, the present study was designed to investigate the molecular mechanism behind the neurological and behavioural changes induced by sodium fluoride in Wistar rats. Material and methodsA total of 24 female Wistar rats, aged six weeks and weighing approximately 150–220 g, were randomly divided into three groups: Group I (control) received reverse osmosis (R.O.) water, Group II received Sodium Fluoride (NaF) at 10 ppm, and Group III received NaF at 50 ppm in their drinking water for 60 days. The animals underwent behavioural tests including the Forced Swim Test (F.S.T.), Open Field Test (OFT), and Novel Object Recognition Test (N.O.R.T.), to assess any alterations in behaviour. After 60 days, the animals were euthanized, and their blood and brain samples were analysed to evaluate biochemical changes by Western Blot/I.H.C. analysis of B.A.X., Bcl2, LC3B, TLR4, PARP1, p53, Caspase, α-Synuclein, PARKIN, NeuN, KI67, DNM-1, and M.F.N. for assessing molecular pathways for toxicity. ResultsImpaired locomotion, memory impairment, and behaviour resembling depression in the animals were evinced by reduced mobility index in the F.S.T., discrimination index in the N.O.R.T., and reduced locomotor activity in the open field test results. Additionally, alterations in antioxidant levels and oxidative stress parameters were observed in the brain. The expression levels of various apoptotic and inflammatory biomarkers (B.A.X., Bcl2, TLR4, PARP1, p53, and Caspase) showed apoptosis in neurons. The confocal studies showed increased expression of inflammatory (α-Synuclein, PARKIN), apoptotic (LC3B, B.A.X., p53, KI67), and mitochondrial dysfunction (NeuN, DNM-1, M.F.N.) markers in fluoride-treated animals. Toxicity was more prominent in 50 ppm of fluoride-treated animals. ConclusionFluoride showed potent neuronal toxicity as evidenced by alterations of various molecular markers.

Dynamics of Stress Biomarker in Cliff Divers during Official Competition

Stress is defined as a reaction of the body to any given stressor, external or internal. These stressors are common among participants in sports. Therefore, this study aimed to determine the dynamics of two stress biomarkers during an official cliff diving competition. The sample of participants included six professional cliff divers (three females and three males). Their salivary cortisol (C) and alpha-amylase (AA) samples were collected during a 3-day competition (four samples on day 1 and six samples on days 2 and 3). The analysis of the results showed a non-significant increase in AA from day one to day three. On the other hand, C has an increase in the first two days (0.58 ± 0.16 µg/mL–0.61 ± 0.23 µg/mL) and then a decrease in the last competition day (0.53 ± 0.23 µg/mL). Analysis of samples collected during each day demonstrates a fluctuation of the biomarkers. For AA, the sample after the training dive on the 2nd day has the highest value (326.34 ± 280.73 U/mL), whereas on day 3, the samples after training and before the competition dive are the highest (364.50 ± 287.13 U/mL; 466.49 ± 218.39 U/mL). Regarding C levels, the sample after the competition dive tends to show the highest values (0.66 ± 0.17 µg/mL; 0.89 ± 0.29 µg/mL; 0.76 ± 0.32 µg/mL, respectively). Furthermore, the correlation between the results of competition and biomarkers is not significant. These results demonstrate how cliff diving competition tends to have a high impact on the sympathetic nervous system, as observed mainly in AA dynamics. One might contend that even though there is no significant physical strain, cliff divers demonstrate heightened stress biomarker levels that could affect their performance and focus while diving.

Effect of adiposity status on salivary Streptococcus mutans and Streptococcus sobrinus.

To investigate the effect of adiposity status, salivary physicochemical parameters, and inflammatory biomarkers on the salivary abundance of the two main cariogenic bacteria Streptococcus mutans and Streptococcus sobrinus among Hong Kong adolescents. This study included 180 adolescents aged 12-15 years from Hong Kong local secondary schools. Anthropometric measurements and oral health examinations were performed. Saliva samples were collected to measure salivary physicochemical parameters, protein biomarker levels, and salivary abundance of Streptococcus mutans, Streptococcus sobrinus, and total bacteria. Adolescents with general overweight/obesity or central obesity had significantly higher salivary Streptococcus mutans abundance and total bacterial load, lower stimulated salivary flow rate, and lower secretory phospholipase A2 group IIA levels than the lean controls. Adolescents with general overweight/obesity (OR = 3.33; 95% CI: 1.28-8.65) and those with central obesity (OR = 2.47; 95% CI: 1.02-6.00) had a significantly higher chance of having high salivary abundance of Streptococcus mutans than the lean controls after adjusting for confounders, with a similar detection rate of salivary Streptococcus sobrinus. General overweight or obesity and central obesity were associated with a high salivary abundance of Streptococcus mutans but had no significant effect on salivary Streptococcus sobrinus.

Severe trauma leads to sustained muscle loss, induced frailty, and distinct temporal changes in myokine and chemokine profiles of older patients

IntroductionSarcopenia is a known risk factor for adverse outcomes across multiple disease states, including severe trauma. Factors such as age, hyperinflammation, prolonged immobilization, and critical illness may not only exacerbate progression of this disease but may also contribute to the development of induced sarcopenia, or sarcopenia secondary to hospitalization. This study seeks to (1) determine the effects of severe traumatic injury on changes in skeletal muscle mass in older adults; (2) test whether changes in skeletal muscle mass are associated with clinical frailty, physical performance, and health-related quality of life; and (3) examine trauma-induced frailty and temporal changes in myokine and chemokine profiles. MethodsA prospective, longitudinal cohort study of 47 critically ill, older (≥45 years) adults presenting after severe blunt trauma was conducted. Repeated measures of computed tomography–based skeletal muscle index, frailty, and quality of life were obtained in addition to selected plasma biomarkers over 6 months. ResultsSevere trauma was associated with significant losses in skeletal muscle mass and increased incidence of sarcopenia from 36% at baseline to 60% at 6 months. Severe trauma also was associated with a transient worsening of induced frailty and reduced quality of life irrespective of sarcopenia status, which returned to baseline by 6 months after injury. Admission biomarker levels were not associated with skeletal muscle index at the time points studied but demonstrated distinct temporal changes across our entire cohort. ConclusionsSevere blunt trauma in older adults is associated with increased incidence of induced sarcopenia and reversible induced frailty. Despite muscle wasting, functional decline is transient, with a return to baseline by 6 months, suggesting a need for holistic definitions of sarcopenia and further investigation into long-term functional outcomes in this population.

Inflammatory Biomarkers and Risk of Psychiatric Disorders

Individuals with psychiatric disorders have been reported to have elevated levels of inflammatory biomarkers, and prospective evidence is limited regarding the association between inflammatory biomarkers and subsequent psychiatric disorders risk. To assess the associations between inflammation biomarkers and subsequent psychiatric disorders risk. This was a prospective cohort study including individuals from the Swedish Apolipoprotein Mortality Risk (AMORIS) cohort, with no prior psychiatric diagnoses and having a measurement of at least 1 inflammatory biomarker. Data from the UK Biobank were used for validation. Longitudinal trajectories of studied biomarkers were visualized before diagnosis of psychiatric disorders in the AMORIS cohort via a nested case-control study. In addition, genetic correlation and mendelian randomization (MR) analyses were conducted to determine the genetic overlap and causality of the studied associations using publicly available GWAS summary statistics. Inflammatory biomarkers, eg, leukocytes, haptoglobin, immunoglobulin G (IgG), C-reactive protein (CRP), platelets, or albumin. Any psychiatric disorder or specific psychiatric disorder (ie, depression, anxiety, and stress-related disorders) was identified through the International Statistical Classification of Diseases, Eighth, Ninth, and Tenth Revision codes. Among the 585 279 individuals (mean [SD] age, 45.5 [14.9] years; 306 784 male [52.4%]) in the AMORIS cohort, individuals with a higher than median level of leukocytes (hazard ratio [HR], 1.11; 95% CI, 1.09-1.14), haptoglobin (HR, 1.13; 95% CI, 1.12-1.14), or CRP (HR, 1.02; 95% CI, 1.00-1.04) had an elevated associated risk of any psychiatric disorders. In contrast, we found an inverse association for IgG level (HR, 0.92; 95% CI, 0.89-0.94). The estimates were comparable for depression, anxiety, and stress-related disorders, specifically, and these results were largely validated in the UK Biobank (n = 485 620). Analyses of trajectories revealed that individuals with psychiatric disorders had higher levels of leukocytes and haptoglobin and a lower level of IgG than their controls up to 30 years before the diagnosis. The MR analysis suggested a possible causal relationship between leukocytes and depression. In this cohort study, inflammatory biomarkers including leukocytes, haptoglobin, CRP, and IgG were associated with a subsequent risk of psychiatric disorders, and thus might be used for high-risk population identification. The possible causal link between leukocytes and depression supports the crucial role of inflammation in the development of psychiatric disorders.

Comprehensive laboratory assessment of lonoctocog alfa versus octocog alfa in severe haemophilia A.

Lonoctocog alfa is a single-chain factor VIII (FVIII) molecule with high binding affinity to von-Willebrand-factor. While it is well known that its plasma activity is underestimated by one-stage clotting assays (OSCA), there is a lack of knowledge on the post-infusion performance of lonoctocog alfa in global coagulation assays or its potential impact on the haemostatic balance in vivo. To characterize lonoctocog alfa versus octocog alfa in pre- and post-infusion samples obtained from patients undergoing repeated investigation of incremental recovery (IR). Eighteen patients with severe haemophilia A (lonoctocog alfa: 10, octocog alfa: 8) were included. A panel of factor-specific and global coagulation assays was applied, comprising a FVIII OSCA, two FVIII chromogenic substrate assays (CSA), rotational thrombelastography and thrombin generation (TG). Potential activation of coagulation was assessed by measuring plasma thrombin markers and levels of activated protein C. Comparable IRs were found for lonoctocog alfa and octocog alfa (2.36 [IU/dL]/[IU/kg] vs. 2.55 [IU/dL]/[IU/kg], respectively). Lonoctocog alfa activities were found to be underestimated by the FVIII OSCA while also the two FVIII CSAs showed statistically significant assay discrepancies on lonoctocog alfa. Effects of both FVIII products on rotational thrombelastography were less distinct than those on TG parameters. No elevated pre- or significantly shifting post-infusion plasma levels of coagulation biomarkers were detected. Lonoctocog alfa and octocog alfa showed comparable recovery and safety in vivo as well as similar impacts on TG in vitro. Observed assay discrepancies on lonoctocog alfa demonstrated variability of results also between different FVIII CSAs.

Monocyte Chemoattractant Protein-1, Inflammatory Biomarkers, and Prognosis of Patients With Ischemic Stroke or Transient Ischemic Attack: Fndings From a Nationwide Registry Study.

Recent Mendelian randomization and meta-analysis highlight the relevance of MCP-1 (monocyte chemoattractant protein-1) in stroke. We aimed to investigate the associations between MCP-1 and clinical outcomes in patients with ischemic stroke or transient ischemic attack and test whether inflammation mediates or jointly contributes to the relationships. A total of 10 700 patients from the Third China National Stroke Registry study were included. Multivariable Cox regression was used for recurrent stroke and all-cause death, and logistic regression was used for poor functional outcome. Mediation analyses were performed to clarify whether inflammation mediates the associations. After adjusting for potential confounders, low MCP-1 level (<337.6 pg/mL) was associated with a reduced risk of all-cause death (hazard ratio [HR], 0.65 [95% CI, 0.51-0.82]) and poor functional outcome (odds ratio, 0.81 [95% CI, 0.70-0.94]) but was not associated with recurrent stroke (HR, 1.10 [95% CI, 0.95-1.27]), compared with high MCP-1 level (≥337.6 pg/mL). The association between MCP-1 and all-cause death was partially mediated by highly sensitive C-reactive protein, interleukin-6, and YKL-40 (Chitinase-3-like protein 1; mediated proportion: 7.4%, 10.5%, and 7.4%, respectively). The corresponding mediated proportion for poor functional outcome was 9.9%, 17.1%, and 7.1%, respectively. Patients with combined high levels of MCP-1 and inflammatory biomarkers had the highest risks of all-cause death and poor functional outcome. Low plasma MCP-1 level was associated with decreased risks of all-cause mortality and poor functional outcome after ischemic stroke or transient ischemic attack. Inflammation partially mediated and jointly contributed to the associations.

Artificial intelligence in cardiovascular medicine: clinical applications.

Clinical medicine requires the integration of various forms of patient data including demographics, symptom characteristics, electrocardiogram findings, laboratory values, biomarker levels, and imaging studies. Decision-making on the optimal management should be based on a high probability that the envisaged treatment is appropriate, provides benefit, and bears no or little potential harm. To that end, personalized risk-benefit considerations should guide the management of individual patients to achieve optimal results. These basic clinical tasks have become more and more challenging with the massively growing data now available; artificial intelligence and machine learning (AI/ML) can provide assistance for clinicians by obtaining and comprehensively preparing the history of patients, analysing face and voice and other clinical features, by integrating laboratory results, biomarkers, and imaging. Furthermore, AI/ML can provide a comprehensive risk assessment as a basis of optimal acute and chronic care. The clinical usefulness of AI/ML algorithms should be carefully assessed, validated with confirmation datasets before clinical use, and repeatedly re-evaluated as patient phenotypes change. This review provides an overview of the current data revolution that has changed and will continue to change the face of clinical medicine radically, if properly used, to the benefit of physicians and patients alike.

Mir-381-3p aggravates ovariectomy-induced osteoporosis by inhibiting osteogenic differentiation through targeting KLF5/Wnt/β-catenin signaling pathway

BackgroundIncreasing evidence shows the pivotal significance of miRNAs in the pathogenesis of osteoporosis. miR-381-3p has been identified as an inhibitor of osteogenesis. This study explored the role and mechanism of miR-381-3p in postmenopausal osteoporosis (PMOP), the most common type of osteoporosis.MethodsBilateral ovariectomy (OVX) rat model was established and miR-381-3p antagomir was administrated through the tail vein in vivo. The pathological changes in rats were assessed through the evaluation of serum bone turnover markers (BALP, PINP, and CTX-1), hematoxylin and eosin (H&E) staining, as well as the expression of osteoblast differentiation biomarkers. Moreover, isolated bone marrow mesenchymal stem cells from OVX-induced rats (OVX-BMMSCs) were utilized to explore the impact of miR-381-3p on osteoblast differentiation. In addition, the target gene and downstream pathway of miR-381-3p were further investigated both in vivo and in vitro.ResultsmiR-381-3p expression was elevated, whereas KLF5 was suppressed in OVX rats. miR-381-3p antagomir decreased serum levels of bone turnover markers, improved trabecular separation, promoted osteoblast differentiation biomarker expression in OVX rats. ALP activity and mineralization were suppressed, and levels of osteoblast differentiation biomarkers were impeded after miR-381-3p overexpression during osteoblast differentiation of OVX-BMMSCs. While contrasting results were found after inhibition of miR-381-3p. miR-381-3p targets KLF5, negatively affecting its expression as well as its downstream Wnt/β-catenin pathway, both in vivo and in vitro. Silencing of KLF5 restored Wnt/β-catenin activation induced by miR-381-3p antagomir.ConclusionmiR-381-3p aggravates PMOP by inhibiting osteogenic differentiation through targeting KLF5/Wnt/β-catenin pathway. miR-381-3p appears to be a promising candidate for therapeutic intervention in PMOP.

Aqueous Humor Cytokines in Idiopathic Epiretinal Membrane: Correlation with Disease Severity.

To analyze the concentration of aqueous humor (AH) cytokines in eyes with idiopathic epiretinal membrane (iERM) and to investigate their potential correlation with disease severity. Retrospective cross-sectional case-control institutional study. A total of 16 eyes of 16 iERM patients and 14 eyes of 14 age-matched healthy controls were enrolled. AH samples were analyzed for various biomarkers using a glass-chip protein array. Cytokines associated with inflammation, fibrosis, angiogenesis, and glial signal transduction were quantified. Significant differences in cytokine concentration were observed between the iERM group and controls, with 19 cytokines elevated in the iERM group (among them IL-6, IL-8, PDGF-AB, PDGF-BB, TGFB-1, TGFB-2, TGFB-3, VEGF A, VEGF C, VEGF D, p < 0,05, 95% confidence interval). Correlation analysis revealed associations between cytokine levels and iERM severity. Notably, stages 2, 3, and 4 of iERM demonstrated increased levels of various biomarkers. This study provides insights into the complex molecular interactions underlying iERM pathogenesis, describing a correlation between neuroinflammation and iERM severity.

Impact of Different Emergency Treatment Methods on Prognosis of Patients with Acute Myocardial Infarction Undergoing Percutaneous Coronary Intervention: Retrospective Study

Purpose: This study aimed to investigate the impact of different emergency treatment methods on the prognosis of patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI). Methods: A retrospective study was conducted involving 114 patients admitted to the hospital between January 2022 and December 2022. The patients were divided into two groups based on their emergency treatment methods: First Transport and Then Treatment Group (n = 56) and Treatment Before Transport Group (n = 58). Baseline characteristics, biomarker levels, echocardiographic findings, curative effects, and 1-year follow-up outcomes were compared between the two groups. Results: Biomarker levels and echocardiographic parameters differed significantly between the two groups, thus indicates potential variations in disease severity and prognosis. Moreover, the 1-year follow-up outcomes showed higher rates of all-cause mortality (16.07% vs. 3.45%, p = 0.022), recurrent myocardial infarction (19.64% vs. 5.17%, p = 0.019), rehospitalization for cardiovascular causes (25.05% vs. 8.62%, p = 0.019), and PCI for new lesions (23.21% vs. 6.92%, p = 0.014) in the First Transport and Then Treatment Group compared with the Treatment Before Transport Group. Conclusion: The timing of emergency treatment methods in patients with AMI undergoing PCI appeared to significantly impact clinical outcomes, echocardiographic parameters, and 1-year follow-up outcomes. Immediate administration of treatment before transport showed potential benefits in mitigating myocardial damage and improving long-term prognosis compared with the approach of transporting the patient to the healthcare facility before initiating treatment.

Exploratory Study Identifies Matrix Metalloproteinase-14 and -9 as Potential Biomarkers of Regorafenib Efficacy in Metastatic Colorectal Cancer.

In identifying biomarkers for anticancer drugs, the lack of objectivity in selecting candidate factors makes interpretation difficult. We performed preclinical analysis and a translational validation study to identify candidate biomarkers for regorafenib efficacy in metastatic colorectal cancer (mCRC). Using in silico COMPARE analysis with a human cancer cell line panel, JFCR39, we selected candidate biomarkers whose expression correlates with regorafenib sensitivity. We validated predictive values in mCRC patients receiving regorafenib (discovery, n = 53) and FTD/TPI (control, n = 16). Blood samples were obtained at baseline (BL), before the second cycle (2nd), and at progressive disease (PD), and biomarker levels were measured using ELISA. Our analysis showed that high matrix metalloproteinase (MMP)-14 expression was associated with a high sensitivity to regorafenib. In the discovery cohort, high MMP-14 levels at BL and PD were correlated with tumor shrinkage and longer progression-free survival (PFS). A subsequent analysis of other related factors further indicated that the patients with decreased MMP-9 levels at the 2nd had higher disease control rates, tumor shrinkage, longer PFS, and overall survival than those with increased changes. These findings were not observed in the control cohort. Our study suggests MMP-14 and MMP-9 may serve as prognostic markers for regorafenib and provide insights into novel combination therapies with anti-MMP-9 agents or FTD/TPI.

Sex-Specific Associations between Thyroid Status, Inflammation and Hemostasis Biomarkers in Patients with Subacute Thyroiditis.

Background: Subacute thyroiditis (SAT) is characterized by profound inflammation and fluctuations in thyroid hormones which may affect the hemostasis balance. This study investigates sex-specific associations between thyroid status, inflammation and hemostasis biomarkers in SAT. Methods: We included 52 patients (40 women and 12 men) treated with non-steroidal anti-inflammatory drugs (NSAID) or methylprednisolone (MPS). Free thyroxine (fT4), thyroid stimulating hormone, C-reactive protein, complete blood count and routine hemostasis parameters were assessed. Results: Both men and women were in hyperthyroid state and had comparable levels of inflammatory biomarkers. A shortened activated partial thromboplastin time (aPTT) was observed in 16.7% of the men and 10% of the women (p = 0.562), and a shortened prothrombin time (PT) was observed in 33% of the men and 12.5% of the women (p = 0.094). In men, aPTT positively correlated with fT4 (r = 0.627; p < 0.05), while PT positively correlated with leukocyte-based inflammatory indices in women (p < 0.05). NSAID-treated patients had lower aPTTs and platelet counts than those treated with MPS (p < 0.05). Principal component analysis extracted "proinflammatory", "prothrombotic" and "antithrombotic" factors, but the "proinflammatory" factor was the independent predictor of elevated fT4 in women (OR = 2.705; p = 0.036). Conclusions: Our data demonstrated sex-specific associations of thyroid status and inflammatory biomarkers with hemostasis parameters in SAT. Routine hemostasis screening tests may help in monitoring the changes in the hemostasis system over the course of SAT.

Appraisal of skeletal maturity indicators with respect to non-invasive biomarkers

Non-invasive salivary biomarkers are being investigated as they may be helpful in predicting skeletal age. This study was conducted to evaluate the correlation between salivary insulin-like growth factor-1, salivary alkaline phosphatase, cervical vertebrae maturation stages and chronological age in the assessment of skeletal age during the growth period. This study also aims to find associations with mandibular base length and maxillary base length. Total 80 eligible subjects aged 7 to 21 years were selected and divided into two gender-specific groups (41 males, 39 females). A further subdivision was made on the basis of six cervical vertebral maturation stages from the lateral cephalogram. The chronological age was given for each subject, and The maxillary base length and the length of the mandibular base was calculated from the impressions on the lateral cephalogram. Saliva samples were collected from each subject to determine salivary IGF-1 and ALP levels using an enzyme-linked immunosorbent assay (ELISA). The data obtained was statistically analysed using SPSS (20.0) software. It was found that the mean IGF-1 activity in saliva was highest at CVMI stage 3 and the highest mean ALP levels in saliva occurred in males at CVMI stage 3 and in females at CVMI stage 4. Mean salivary ALP and IGF-1 levels correlate well with . Salivary ALP levels show a correlation with chronological age and could also be used as a diagnostic model to predict cervical stage. The diagnostic levels of certain biomarkers that appear in human saliva are representative of an individual's circumpubertal growth spurt. The collective pattern of increase and decrease in the sample during the circumpubertal stages is essential to study for orthodontic diagnosis and treatment planning.

Tau pathology mediated the plasma biomarkers and cognitive function in patients with mild cognitive impairment

Glial fibrillary acidic protein (GFAP) and neurofilament light (NfL) are putative non-amyloid biomarkers indicative of ongoing inflammatory and neurodegenerative disease processes. Hence, this study aimed to demonstrate the relationship between plasma biomarkers (GFAP and NfL) and 18F-AV-1451 tau PET images, and to explore their effects on cognitive function. Ninety-one participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database and 20 participants from the Shanghai Action of Prevention Dementia for the Elderly (SHAPE) cohort underwent plasma biomarker testing, 18F-AV-1451 tau PET scans and cognitive function assessments. Within the ADNI, there were 42 cognitively normal (CN) individuals and 49 with mild cognitive impairment (MCI). Similarly, in the SHAPE, we had 10 CN and 10 MCI participants. We calculated the standardized uptake value ratios (SUVRs) for the regions of interest (ROIs) in the 18F-AV-1451 PET scans. Using plasma biomarkers and regional SUVRs, we trained machine learning models to differentiate between MCI and CN subjects with ADNI database and validated in SHAPE.Results showed that eight selected variables (including left amygdala SUVR, right amygdala SUVR, left entorhinal cortex SUVR, age, education, plasma NfL, plasma GFAP, plasma GFAP/ NfL) identified by LASSO could differentiate between the MCI and CN individuals, with AUC ranging from 0.783 to 0.926. Additionally, cognitive function was negatively associated with the plasma biomarkers and tau deposition in amygdala and left entorhinal cortex. Increased tau deposition in amygdala and left entorhinal cortex were related to increased plasma biomarkers. Moreover, tau pathology mediated the effect of plasma biomarkers level on the cognitive decline. The present study provides valuable insights into the association among plasma markers (GFAP and NfL), regional tau deposition and cognitive function. This study reports the mediation effect of brain regions tau deposition on the plasma biomarkers level and cognitive function, indicating the significance of tau pathology in the MCI patients.

Association of biomarkers and Barthel Index with occurrence of age-related adverse health outcomes in individuals with diabetes.

The clinical significance of age-related biomarkers in patients with diabetes has not been fully elucidated. In this study, we aimed to establish models to predict the progression of aging in patients with diabetes using biomarkers. This single-center, retrospective cohort study included 115 Japanese patients with diabetes aged ≥60 years. Age-related adverse health outcomes were defined as emergency hospitalization, any increase in the level of nursing care certification, admission to a nursing home or death. The associations of age-related biomarker levels (adiponectin, growth differentiation factor 15 [GDF15], C-X-C motif chemokine ligand 9 and apelin) and clinical indicators with age-related adverse health outcomes were evaluated. Factors that predominantly influenced the occurrence of age-related adverse health outcomes were explored using the Cox proportional hazards model. The mean age of the 115 participants was 73 years, 50.6% were men, the mean body mass index and hemoglobin A1c level were 25.3 kg/m2 and 9.79%, respectively. There were 26 age-related adverse health outcomes during the study period (median 1.93, range 0-4.65 years). In a model combining clinical indicators and biomarkers, including the Barthel Index, GDF15 and adiponectin, the occurrence of age-related adverse health outcomes was found to be significantly associated with GDF15 and Barthel Index. The group with both GDF15 and adiponectin levels higher than the median proved to be significantly higher than the group with both lower. The measurement of GDF15 and adiponectin levels and the Barthel Index might be useful for predicting age-related adverse health outcomes in patients with diabetes.

Age-Dependent Differences in Blood Levels of Glial Fibrillary Acidic Protein but Not Ubiquitin Carboxy-Terminal Hydrolase L1 in Children.

Despite the growing evidence of the clinical utility of blood-brain biomarkers in adults with traumatic brain injury (TBI), less is known about the performance of these biomarkers in children. We characterize age-dependent differences in levels of ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) and glial fibrillary acidic protein (GFAP) in children without TBI. Plasma biobank specimens from children and adolescents aged 0-<19 years without TBI were obtained, and UCH-L1 and GFAP levels were quantified. The relationship between age and biomarker expression was determined using previously defined aged epochs (<3.5 years, 3.5 years to <11 years, 11 years and older), then biomarker levels were compared with established thresholds for ruling out the need for a head CT in adults with a mild TBI (mTBI) (UCH-L1 400 pg/mL, GFAP 35 pg/mL). The age range of the 366 control patients was 3 months-18 years. There was a significant negative association between age and GFAP but not UCH-L1. Only 1.4% of samples exceeded the UCH-L1 cutoff; however, 20% of samples exceeded the GFAP cutoff and 100% children younger than 3.5 years had values that exceeded the cutoff. Age seems to modify physiologic plasma GFAP levels. Diagnostic cutoffs for TBI based on GFAP but not UCH-L1 and may need to be adjusted in children younger than 11 years.

Diagnostic accuracy of salivary hemoglobin, lactate dehydrogenase and Interleukin-6 to determine chronic periodontitis and tooth loss in type 2 diabetics

BackgroundSalivary Hemoglobin (SH) has emerged as the mainstay non-invasive and a practicable screening method for Chronic Periodontitis. Current research aims to comprehensively assess the diagnostic value of Salivary Hb (SH) in comparison with Salivary IL-6 (SIL-6) and levels of Salivary lactate dehydrogenase enzyme (SLDH) amongst Type II Diabetes subjects having Chronic Periodontitis (CP) and associated tooth loss. Materials and methodsIn this cross-sectional comparative investigation, 240 individuals with at least 15 remaining teeth, ranging in age from 30 to 70, were chosen and Group I controls were defined as follows: healthy (HbA1c levels ≤6.4 %) with no CP; Group II included chronic periodontitis and non-T2DM (HbA1c ≤ 6.4 %); Group III included T2DM (HbA1c ≥ 6.5 %) and CP; and Group IV included T2DM (HbA1c ≥ 6.5 %) with periodontitis-related tooth loss. ELISA colorimetric assay was used to quantify the results using the unstimulated whole saliva of fasting participants. Tukey's post hoc test was used for statistical analysis following Analysis of Variance (ANOVA), and Sensitivity and Specificity were computed following the determination of the correlation coefficient. ResultsOne-way ANOVA comparing Biomarker levels across the four groups revealed a statistically significant difference (F = 68.013) (p = 0.0001). Tukey's multiple post hoc yielded a significant difference between groups with least mean average biomarker levels observed among the controls (Group1) and maximum with group IV. Diagnostic Accuracy to discriminate between CP in T2DM & Controls with SH surpassed that of SIL-6 & SLDH, Receiver operating characteristic (ROC) curve depicted an overall sensitivity of 67.62 %, specificity of 80 % and accuracy of 74 % in T2DM subjects with tooth loss for the identification and assessment of CP. ConclusionEstimates of Salivary Hemoglobin can assume an important role in comparison to SIL-6 & SLDH in determining the degree of periodontitis, including tooth loss, and identifying elevated glycemic levels. Advanced detection and monitoring can be ensured by routine use in dental offices and general practice.

Association of novel biomarkers of systemic inflammation with atherosclerosis and its severity

Aim. To compare the levels of novel biomarkers of systemic inflammation in pati­ents with and without atherosclerosis, as well as between groups of patients with atherosclerosis of different severity.Material and methods. Patients with suspected coronary artery disease after selective coronary angiography were included. The analysis included 901 patients with mean age of 61±10 years (men, 60% (n=549)). The patients were divided into two following groups: with and without atherosclerosis. The Propensity Score Matching method was used to adjust for baseline clinical differences.Results. In the group with atherosclerosis, the values of the systemic inflam­mation response index (SIRI), systemic immune-inflammation index (SII) and ag­gregate index of systemic inflammation (AISI) were significantly higher than in patients without atherosclerosis: 0,906 (0,632; 1,36) vs 0,745 (0,519; 1,02), p&lt;0,001; 457 (350; 641) vs 425 (313; 547), p=0,005 and 233 (148; 346) vs 179 (121; 263), p&lt;0,001, respectively. ROC analysis showed the following threshold values of the studied parameters: for SIRI &gt;1,05, area under the curve (AUC) confidence interval (CI) — 0,615 (0,571-0,658), p&lt;0,001, sensitivity — 42,6%, specificity — 77,3%; for SII &gt;368, AUC CI — 0,572 (0,528-0,616), p=0,004, sensitivity — 72,1%, specificity — 43,4%; for AISI &gt;248, AUC CI — 0,604 (0,560-0,647), p&lt;0,001, sensitivity 47,4%, specificity 71,1%. SIRI had the highest AUC. When comparing 6 groups according to the Coronary Artery Surgery Study (CASS) classification, significant differences were found in SIRI and AISI, p&lt;0,001 and p=0,0016, respectively. However, these differences did not have a logical pattern.Conclusion. Novel markers of systemic inflammation (SIRI, SII and AISI) were significantly higher in patients with confirmed atherosclerosis than in patients without it. There are following threshold levels associated with atherosclerosis: for SIRI &gt;1,05, for SII &gt;368, for AISI &gt;248.

Neuroprotective role of chlorogenic acid against hippocampal neuroinflammation, oxidative stress, and apoptosis following acute seizures induced by pentylenetetrazole.

This study investigated the neuroprotective effect of chlorogenic acid (CGA) on pentylenetetrazole (PTZ)-induced acute epileptic seizures in mice. Epileptic animals received CGA (200mg/kg) or sodium valproate (standard antiepileptic agent, 200mg/kg) for four weeks. Results revealed that pre-administration of CGA significantly reversed the behavioral changes following pentylenetetrazole (PTZ) injection. Further, CGA pre-treatment caused significant increases in acetylcholinesterase (AChE) activity and brain-derived neurotrophic factor (BDNF) levels, along with marked increases in dopamine, norepinephrine, and serotonin levels. Additionally, the increased antioxidant enzymes activities, along with higher glutathione (GSH) contents and upregulated nuclear factor erythroid 2-related factor 2 (Nrf2) gene expression, were indicative of a notable improvement in the cellular antioxidant defense in mice treated with CGA. These results were associated with lowered malondialdehyde (MDA) and nitric oxide (NO) levels. Moreover, epileptic mice that received CGA showed significant declines in the content of interleukin-1 beta (IL-1β), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and nuclear factor kappa-B (NF-κB), besides downregulating inducible nitric oxide synthase (iNOS) expression. Remarkably, CGA counteracted hippocampal apoptosis by lessening the levels of pro-apoptotic biomarkers [Bcl-2-associated X protein (Bax) and caspase-3] and increasing the anti-apoptogenic marker level of B-cell lymphoma 2 (Bcl-2). The hippocampal histopathological findings corroborated the abovementioned changes. In sum, these findings suggest that CGA could mediate the neuroprotective effect against PTZ-induced epilepsy via modulation of neurotransmitters, oxidative damage, neuroinflammation, and apoptosis. CGA, therefore, could be considered a valuable antiepileptic therapeutic supplement.