Importance of evaluation of heart-type fatty acid binding protein (H-FABP) in COVID-19 Patients.

INTRODUCTION: Recent studies have documented the cardiovascular consequences of acute coronavirus disease 2019 (COVID-19), although one of the early cardiac markers that can be used for diagnosis, the heart-type fatty acid-binding protein (H-FABP), has not been covered. Through the evaluation of H-FABP levels, we aim to contribute to the early diagnosis and treatment of cardiac problems in COVID-19 infection patients. METHODOLOGY: Seventy-five patients who were admitted to the emergency department of Mehmet Akif Ersoy Hospital with a complaint of chest pain in the last 6 hours and whose corona PCR tests were positive, were included in our study as the case group and 60 healthy volunteers as the control group. The routine cardiac markers such as creatine kinase MB (CK-MB) cardiac troponin T (cTnT), and H-FABP levels were analyzed by routine laboratory methods. RESULTS: The mean age and gender distributions of the groups did not differ statistically (p > 0.05). CK-MB, cTnT, and H-FABP measurements were statistically different between the groups (p = 0.001; p < 0.01). CONCLUSIONS: The relationship between AMI and COVID-19 with routine cardiac markers is already supported by recent studies. We also evaluated H-FABP levels in our study, as it affects the prognosis of the disease independent of the chronic disease history. At the same time, we showed that H-FABP levels increase earlier than routine cardiac markers, so it will be useful for COVID-19 patients with cardiac complaints.

Scalable synthesis of Au@CeO2 nanozyme for development of colorimetric lateral flow immunochromatographic assay to sensitively detect heart-type fatty acid binding protein.

Nanozymes with core@shell nanostructure are considered promising biolabeling materials for their multifunctional properties. In this work, a simple one-pot strategy has been proposed for scalable synthesis of gold@cerium dioxide core@shell nanoparticles (Au@CeO2 NPs) with strong localized surface plasmon resonance (LSPR) absorption and high peroxidase-like catalytic activity by redox reactions of Ce3+ ions and AuCl4- ions in diluted ammonia solution under room temperature. A colorimetric lateral flow immunochromatographic assay (LFIA) has been successfully fabricated for sensitive detection of heart-type fatty acid binding protein (H-FABP, an early cardiac biomarker) by using the Au@CeO2 NPs as reporters. The as-developed LFIA with Au@CeO2 NP reporter (termed as Au@CeO2-LFIA) exhibits a dynamic range of nearly two orders of magnitude, and a limit of detection (LOD) as low as 0.35 ng mL-1 H-FABP with nanozyme-triggered 3,3',5,5'-tetramethylbenzidine (TMB) colorimetric amplification. Furthermore, the practicality of Au@CeO2-LFIA has been demonstrated by profiling the concentrations of H-FABP in 156 blood samples of acute myocardial infarction (AMI) patients, and satisfactory results are obtained.

Multimetal-Based Metal-Organic Framework System for the Sensitive Detection of Heart-Type Fatty Acid Binding Protein in Electrochemiluminescence Immunoassay.

In this work, an electrochemiluminescence (ECL) quenching system using multimetal-organic frameworks (MMOFs) was proposed for the sensitive and specific detection of heart-type fatty acid-binding protein (H-FABP), a marker of acute myocardial infarction (AMI). Bimetallic MOFs containing Ru and Mn as metal centers were synthesized via a one-step hydrothermal method, yielding RuMn MOFs as the ECL emitter. The RuMn MOFs not only possessed the strong ECL performance of Ru(bpy)32+ but also maintained high porosity and original metal active sites characteristic of MOFs. Moreover, under the synergistic effect of MOFs and Ru(bpy)32+, RuMn MOFs have more efficient and stable ECL emission. The trimetal-based MOF (FePtRh MOF) was used as the ECL quencher because of the electron transfer between FePtRh MOFs and RuMn MOFs. In addition, active intramolecular electron transfer from Pt to Fe or Rh atoms also occurred in FePtRh MOFs, which could promote intermolecular electron transfer and improve electron transfer efficiency to enhance the quenching efficiency. The proposed ECL immunosensor demonstrated a wide dynamic range and a low detection limit of 0.01-100 ng mL-1 and 6.8 pg mL-1, respectively, under optimal conditions. The ECL quenching system also presented good specificity, stability, and reproducibility. Therefore, an alternative method for H-FABP detection in clinical diagnosis was provided by this study, highlighting the potential of MMOFs in advancing ECL technology.

Fatty acid-binding protein-3 and renal function decline in patients with chronic coronary syndrome.

BACKGROUND: Renal dysfunction is common in patients with coronary artery disease. Due to the shared vascular pathogenesis between the two conditions, novel biomarkers such as the fatty acid-binding protein-3 (FABP-3) have been proposed for diagnosis and prognosis prediction. This multicentre prospective cohort study investigates the association between FABP-3 and renal dysfunction. HYPOTHESIS: We hypothesized that higher FABP-3 levels are correlated to worse renal outcome. METHODS: Patients with chronic coronary syndrome were classified into three groups based on the initial serum FABP-3 levels. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation was used to estimate the patient's renal function. Renal events were defined as >25% and >50% decline in estimated glomerular filtration rate (eGFR). Cox multivariable regression was employed to delineate the correlation between FABP-3 and renal dysfunction. RESULTS: A total of 1606 subjects were included. During a mean follow-up of 35.9 months, there were 239 patients with eGFR >25% reduction and 60 patients with >50% reduction. In the Kaplan-Meier survival curve and log-rank test, increased levels of FABP-3 were significantly correlated with eGFR >25% reduction (p < .001) and >50% reduction (p < .001). Multivariate Cox regression model revealed that subjects with higher FABP-3 exhibited a greater risk of eGFR >25% reduction (Group 2: hazard ratio [HR] = 2.328, 95% confidence interval [CI] = 1.521-3.562, p < .001; Group 3: HR = 3.054, 95% CI = 1.952-4.776, p < .001) and >50% reduction (Group 3: HR = 4.838, 95% CI = 1.722-13.591, p = .003). CONCLUSIONS: Serum FABP-3 may serve as a novel biomarker to predict eGFR decline in patients with chronic coronary syndrome.

The oxidized phospholipid PGPC impairs endothelial function by promoting endothelial cell ferroptosis via FABP3.

Ferroptosis is a novel cell death mechanism that is mediated by iron-dependent lipid peroxidation. It may be involved in atherosclerosis development. Products of phospholipid oxidation play a key role in atherosclerosis. 1-palmitoyl-2-glutaroyl-sn-glycero-3-phosphocholine (PGPC) is a phospholipid oxidation product present in atherosclerotic lesions. It remains unclear whether PGPC causes atherosclerosis by inducing endothelial cell ferroptosis. In this study, human umbilical vein endothelial cells (HUVECs) were treated with PGPC. Intracellular levels of ferrous iron, lipid peroxidation, superoxide anions (O2•-), and glutathione were detected, and expression of fatty acid binding protein-3 (FABP3), glutathione peroxidase 4 (GPX4), and CD36 were measured. Additionally, the mitochondrial membrane potential (MMP) was determined. Aortas from C57BL6 mice were isolated for vasodilation testing. Results showed that PGPC increased ferrous iron levels, the production of lipid peroxidation and O2•-, and FABP3 expression. However, PGPC inhibited the expression of GPX4 and glutathione production and destroyed normal MMP. These effects were also blocked by ferrostatin-1, an inhibitor of ferroptosis. FABP3 silencing significantly reversed the effect of PGPC. Furthermore, PGPC stimulated CD36 expression. Conversely, CD36 silencing reversed the effects of PGPC, including PGPC-induced FABP3 expression. Importantly, E06, a direct inhibitor of the oxidized 1-palmitoyl-2-arachidonoyl-phosphatidylcholine IgM natural antibody, inhibited the effects of PGPC. Finally, PGPC impaired endothelium-dependent vasodilation, ferrostatin-1 or FABP3 inhibitors inhibited this impairment. Our data demonstrate that PGPC impairs endothelial function by inducing endothelial cell ferroptosis through the CD36 receptor to increase FABP3 expression. Our findings provide new insights into the mechanisms of atherosclerosis and a therapeutic target for atherosclerosis.

Biomarker array for prediction of acute kidney injury after percutaneous coronary intervention for patients who had acute ST segment elevation myocardial infarction.

Acute kidney injury (AKI) is a common complication after Percutaneous Coronary Intervention (PCI) for ST segment elevation myocardial infarction (STEMI) and is associated with poor outcomes. AKI is diagnosed by the dynamic change of serum Cr, but it could not predict AKI. This study aimed to evaluate a biomarker array that may fulfill this shortage. Setting: Cardiology Department, Tanta University Hospital. Design: Prospective interventional study included 280 acute STEMI patients who underwent emergency PCI. Serial samples of blood and urine were obtained at the time of admission to the hospital (T0) and PCI unit (T1) and at 12 h and 72 h (T12 and T72) after coronary revascularization to estimate levels of serum Cr, creatine phosphokinase, and heart-type fatty acid-binding protein (H-FABP) and calculation of neutrophil/lymphocyte ratio (NLR) and urinary liver-type FABP (L-FABP). AKI was diagnosed according to the recommendations of the European Renal Best Practice as the times of increased serum Cr concerning baseline level. 85 patients developed AKI. Regression analyses defined a high NLR ratio in the T0 sample as the most significant predictor for early AKI diagnosed at T1 time, while high NLR and serum H-FABP levels in T1 samples as the significant predictors for AKI defined at T12 time. However, high urinary L-FABP levels in T12 samples and high NLR are significant predictors for AKI at T72 time. Combined estimations of serum H-FABP and urinary L-FABP with the calculation of NLR could predict the oncoming AKI and discriminate its pathogenesis. The study protocol was approved by the Local Ethical Committee at Tanta Faculty of Medicine by approval number: 35327/3/22. For blindness purposes, the authors will be blinded about the laboratory results till the end of 72 h after revascularization and the clinical pathologist will be blinded about the indication for the requested investigations.

Outlier Analysis for Acute Blood Biomarkers of Moderate and Severe Traumatic Brain Injury.

Blood biomarkers have been studied to improve the clinical assessment and prognostication of patients with moderate-severe traumatic brain injury (mo/sTBI). To assess their clinical usability, one needs to know of potential factors that might cause outlier values and affect clinical decision making. In a prospective study, we recruited patients with mo/sTBI (n = 85) and measured the blood levels of eight protein brain pathophysiology biomarkers, including glial fibrillary acidic protein (GFAP), S100 calcium-binding protein B (S100B), neurofilament light (Nf-L), heart-type fatty acid-binding protein (H-FABP), interleukin-10 (IL-10), total tau (T-tau), amyloid ß40 (Aß40) and amyloid ß42 (Aß42), within 24 h of admission. Similar analyses were conducted for controls (n = 40) with an acute orthopedic injury without any head trauma. The patients with TBI were divided into subgroups of normal versus abnormal (n = 9/76) head computed tomography (CT) and favorable (Glasgow Outcome Scale Extended [GOSE] 5-8) versus unfavorable (GOSE <5) (n = 38/42, 5 missing) outcome. Outliers were sought individually from all subgroups from and the whole TBI patient population. Biomarker levels outside Q1 - 1.5 interquartile range (IQR) or Q3 + 1.5 IQR were considered as outliers. The medical records of each outlier patient were reviewed in a team meeting to determine possible reasons for outlier values. A total of 29 patients (34%) combined from all subgroups and 12 patients (30%) among the controls showed outlier values for one or more of the eight biomarkers. Nine patients with TBI and five control patients had outlier values in more than one biomarker (up to 4). All outlier values were > Q3 + 1.5 IQR. A logical explanation was found for almost all cases, except the amyloid proteins. Explanations for outlier values included extremely severe injury, especially for GFAP and S100B. In the case of H-FABP and IL-10, the explanation was extracranial injuries (thoracic injuries for H-FABP and multi-trauma for IL-10), in some cases these also were associated with abnormally high S100B. Timing of sampling and demographic factors such as age and pre-existing neurological conditions (especially for T-tau), explained some of the abnormally high values especially for Nf-L. Similar explanations also emerged in controls, where the outlier values were caused especially by pre-existing neurological diseases. To utilize blood-based biomarkers in clinical assessment of mo/sTBI, very severe or fatal TBIs, various extracranial injuries, timing of sampling, and demographic factors such as age and pre-existing systemic or neurological conditions must be taken into consideration. Very high levels seem to be often associated with poor prognosis and mortality (GFAP and S100B).

A multiplexed immunochemical microarray for the determination of cardiovascular disease biomarkers.

A fluorescence antibody microarray has been developed for the determination of relevant cardiovascular disease biomarkers for the analysis of human plasma samples. Recording characteristic protein molecular fingerprints to assess individual's states of health could allow diagnosis to go beyond the simple identification of the disease, providing information on its stage or prognosis. Precisely, cardiovascular diseases (CVDs) are complex disorders which involve different degenerative processes encompassing a collection of biomarkers related to disease progression or stage. The novel approach that we propose is a fluorescent microarray chip has been developed accomplishing simultaneous determination of the most significant cardiac biomarkers in plasma aiming to determine the CVD status stage of the patient. As proof of concept, we have chosen five relevant biomarkers, C-reactive protein (CRP) as biomarker of inflammation, cystatin C (CysC) as biomarker of renal failure that is directly related with heart failure, cardiac troponin I (cTnI) as already established biomarker for cardiac damage, heart fatty acid binding protein as biomarker of ischemia (H-FABP), and finally, NT-proBNP (N-terminal pro-brain natriuretic peptide), a well-established heart failure biomarker. After the optimization of the multiplexed microarray, the assay allowed the simultaneous determination of 5 biomarkers in a buffer solution reaching LODs of 15 ± 5, 3 ± 1, 24 ± 3, 25 ± 3, and 3 ± 1 ng mL-1, for CRP, CysC, H-FABP, cTnI, and NT-proBNP, respectively. After solving the matrix effect, and demonstrating the accuracy for each biomarker, the chip was able to determine 24 samples per microarray chip. Then, the microarray has been used on a small pilot clinical study with 29 plasma samples from clinical patients which suffered different CVD and other related disorders. Results show the superior capability of the chip to provide clinical information related to the disease in terms of turnaround time (1 h 30 min total assay and measurement) and amount of information delivered in respect to reference technologies used in hospital laboratories (clinical analyzers). Despite the failure to detect c-TnI at the reported threshold, the microarray technology could be a powerful approach to diagnose the cardiovascular disease at early stage, monitor its progress, and eventually providing information about an eminent potential risk of suffering a myocardial infarction. The microarray chip here reported could be the starting point for achieving powerful multiplexed diagnostic technologies for the diagnosis of CVDs or any other pathology for which biomarkers have been identified at different stages of the disease.

Anti bacterial function of secreted human FABP3.

FABP3 belongs to a large family of cytoplasmic fatty acid binding proteins that are expressed in a tissue-specific manner. It is predominantly expressed in breast, muscle and heart. During our exploratory studies on the role of FABP3 in tumorigenesis and our consequent attempts to study the molecular mechanism responsible for the oncogenic potential of FABP3, we came across an unexpected role of FABP3 as an anti-bacterial protein. Presence of the protein was detected in culture media of cell lines stably over-expressing human FABP3. Conditioned medium from these FABP3 over-expressing cells exerted a distinct anti-bacterial activity against E. coli. Our results indicate that binding of FABP3 to the bacterial cell surface contributes to its anti-bacterial activity. Incubation of E. coli bacterial cells with FABP3 protein led to disruption of the physical integrity of bacterial cell membrane causing leakage of cellular components. Further, in silico analysis predicted strong binding of FABP3 to the antibiotic binding sites on the bacterial ribosome. Interestingly, we found that FABP3 is a naturally occurring secretory protein present in milk in abundance as confirmed by western blot and ELISA. Thus, our experimental data together with in silico analysis suggests that FABP3 is secreted in milk, has an anti-bacterial function, shows activity against E. coli by disrupting bacterial membrane and targeting the ribosome, and may play a protective role against bacterial infection in newborns.

Circulating H-FABP as a biomarker of frailty in patients with chronic heart failure.

Increased vulnerability to physiologic stressors, termed frailty, is a common occurrence in patients with chronic heart failure (CHF). However, the definite biomarkers to assess frailty in CHF patients are not known. Here, we assessed the frailty phenotype and its potential association with heart failure (HF) markers in CHF patients. We categorized controls (n = 59) and CHF patients (n = 80), the participants, into robust, pre-frail, and frail based on the cardiovascular health study (CHS) frailty index. The plasma levels of HF markers, including tumorigenicity 2 (s-ST2), galectin-3, and heart-type fatty acid binding protein (H-FABP), were measured and correlated with frailty phenotype and cardiac function. The levels of plasma s-ST2, galectin-3, and H-FABP were profoundly elevated in CHF patients. Conversely, the frailty index scores were significantly lower in ischemic and non-ischemic CHF patients versus controls. Of the assessed HF markers, only H-FABP was positively correlated (r2 = 0.07, P = 0.02) with the frailty score in CHF patients. Collectively, these observations suggest that circulating H-FABP may serve as a biomarker of frailty in CHF patients.

Serum levels of soluble suppression of tumorigenicity 2 (sST2) and heart-type fatty acid binding protein (H-FABP) independently predict in-hospital mortality in geriatric patients with COVID-19.

Elevation of cardiac damage biomarkers is associated with adverse clinical outcomes and increased mortality in COVID-19 patients. This study assessed the association of admission serum levels of sST2 and H-FABP with in-hospital mortality in 191 geriatric patients (median age 86 yrs., IQR 82-91 yrs.) with COVID-19 and available measures of hs-cTnT and NT-proBNP at admission. Cox proportional hazards models were utilized to predict in-hospital mortality, considering clinical/biochemical confounders as covariates. A composite cardiac score was calculated to improve predictive accuracy. Patients deceased during their hospital stay (26%) exhibited higher levels of all biomarkers, which demonstrated good discrimination for in-hospital mortality. Addition of sST2 and H-FABP significantly improved the discriminatory power of hs-cTnT and NT-proBNP. The composite cardiac score (AUC=0.866) further enhanced the predictive accuracy. Crude and adjusted Cox regressions models revealed that both sST2 and H-FABP were independently associated with in-hospital mortality (HR for sST2 ≥129 ng/mL, 4.32 [1.48-12.59]; HR for H-FABP ≥18 ng/mL, 7.70 [2.12-28.01]). The composite cardiac score also independently correlated with in-hospital mortality (HR for 1-unit increase, 1.47 [1.14-1.90]). In older patients with COVID-19, sST2 and H-FABP demonstrated prognostic value, improving the predictive accuracy of the routinely assessed biomarkers hs-cTnT and NT-proBNP.

Electroacupuncture ameliorates cardiac dysfunction in myocardial ischemia model rats: a potential role of the hypothalamic-pituitary-adrenal axis.

OBJECTIVE: To verify the hypothesis that electroacupuncture inhibits the hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis regulating the expression of glial fibrillary acidic protein (GFAP) in the hippocampus of acute myocardial ischemia (AMI) rats. METHODS: Sixty-six healthy male Sprague-Dawley rats were randomly divided into five groups: Sham, AMI (Model), electroacupuncture at Shenmen (HT7)-Tongli (HT5) segment (EA), non-acupoint electroacupuncture (Control), and Model + corticosterone (Model + CORT). AMI was induced occlusion of the left anterior descending coronary artery, followed by 3 d of electroacupuncture at Shenmen (HT7)-Tongli (HT5) segment. In the Control group, electroacupuncture was applied at points lying 5 and 10 mm from the base of the tail. The AMI + CORT group was injected with CORT (20 mg/kg) in saline. Hemorheology, electrocardiography (ECG), hematoxylin and eosin staining, and expression of glycogen phosphorylase BB (GPBB) and heart-type fatty acid-binding protein (H-FABP) were used to assess cardiac function. The effects of adrenocorticotropic hormone (ACTH) and CORT were evaluated by enzyme-linked immunosorbent assay. Protein expression in the Sham and Model groups were screened by tandem mass tag-based quantitative proteomics analysis. Protein expression was evaluated by Western blotting (vimentin and GFAP) and immunofluorescence staining (GFAP). RESULTS: Compared with the Sham group, the hemorheology indicators, heart rate, ECG-ST segment elevation, and GPBB and H-FABP levels were higher in Model rats. The EA group showed reductions in these indicators compared with the Model group. Similarly, in Model rats, the expression of ACTH and CORT were significantly increased compared with the Sham group. The EA group also showed reduced expression of ACTH and CORT. Importantly, proteomics analysis showed that vimentin was differentially expressed in Model rats. Compared with the Sham group, vimentin and GFAP expression in the hippocampus was increased in the Model group but decreased in the AMI + EA group. Additionally, intraperitoneal injection of CORT aggravated the expression of GPBB, H-FABP and GFAP. CONCLUSIONS: Our results suggested that electroacupuncture may protect against cardiac injury induced by AMI through regulation of HPA axis hyperactivity, and that hippocampal GFAP may play an important role in the regulation.

Truxillic acid monoamides as fatty acid binding protein 5 inhibitors.

Fatty acid binding proteins (FABPs) are intracellular chaperones that deliver bioactive lipids to cytosolic enzymes and nuclear receptors, thereby regulating diverse biological functions. FABP5 is a member of the FABP family that mediates endocannabinoid transport and inactivation, with pharmacological or genetic FABP5 inhibition conferring antinociceptive effects. Consequently, FABP5 inhibitors have emerged as promising analgesics and demonstrate antinociceptive activity in models of pain. Recently developed FABP5 inhibitors based upon the α-truxillic acid monoester (TAME) scaffold demonstrate high affinities for FABP5 but are commonly accompanied by reduced selectivity against related FABPs, notably FABP3 that is expressed in the heart, highlighting the need to identify additional scaffolds that afford enhanced selectivity while maintaining FABP5 potency. Here, we describe the synthesis and biological evaluation of truxillic acid monoamides (TAMADs) as potent, selective, and efficacious FABP5 inhibitors. Combining in silico molecular docking and in vitro binding assay approaches, our findings demonstrate that TAMADs exhibit exceptional selectivity against FABP3 and several compounds attain high FABP5 affinities. Examination of antinociceptive activity revealed that TAMADs and their corresponding TAMEs demonstrate comparable efficacy and temporal activity profiles in vivo. These results position TAMAD as a suitable scaffold for the development of FABP5 inhibitors with diminished FABP3 cross-reactivity.

The independent prediction study of the effect of heart-type fatty acid binding protein on the severity and long-term cardiac function in Covid-19 patients.

The study was conducted to assess the predictive ability of the heart-type fatty acid binding protein (HFABP) on the severity and long-term cardiac function of Covid-19 infected persons. In the case of negative HsTn-T, we determined whether HFABP was related to the severity of Covid-19 or it was the long-term impact of cardiac function. Chi-square test and t-test were used to evaluate whether HFABP level was an independent predictor of myocardial injury and whether it was related to the severity of Covid-19 and the long-term impact of cardiac function. Among the 20 patients in each of the two groups (mild and severe), 27.5% of all had elevated HFABP. Two were HFABP positive in the mild group, and nine were HFABP positive in the severe group, with a significant difference between the two groups (P=0.013). The mean serum level of HFABP in the mild group was 3.96 ±1.80, compared with 6.70±3.77 in the severe group, with a significant difference between the two groups (P=0.003). In addition, after two years of follow-up, there was a statistically significant difference in the changes of cardiac function between the HFABP-positive group and the HFABP-negative group (P=0.037). These data indicate that among HsTn-T-negative Covid-19 patients, HFABP is a more sensitive and independent predictor of myocardial damage, and it is useful for distinguishing mild and severe Covid-19. The level of HFABP has a significant effect on the long-term changes of heart function in Covid-19 patients.

Evaluation of circulating insulin-like growth factor-1, heart-type fatty acid-binding protein, and endotrophin levels as prognostic markers of COVID-19 infection severity.

BACKGROUND: Coronavirus Disease 2019 (COVID-19) is a worldwide pandemic challenge spreading enormously within a few months. COVID-19 is characterized by the over-activation of the immune system causing cytokine storm. Insulin-like growth factor-1 (IGF-1) pathway can regulate the immune response via interaction with various implicated cytokines. Heart-type fatty acid-binding protein (H-FABP) has been shown to promote inflammation. Given the fact that coronavirus infections induce cytokines secretion leading to inflammatory lung injury, it has been suggested that H-FABP levels are affected by COVID-19 severity. Moreover, endotrophin (ETP), the cleavage product of collagen VI, may be an indicator of an overactive repair process and fibrosis, considering that viral infection may predispose or exacerbate existing respiratory conditions, including pulmonary fibrosis. This study aims to assess the prognostic capacity of circulating IGF-1, HFABP, and ETP, levels for COVID-19 severity progression in Egyptian patients. METHODS: The study cohort included 107 viral RNA-positive patients and an equivalent number of control individuals with no clinical signs of infection. Clinical assessments included profiling of CBC; serum iron; liver and kidney functions; inflammatory markers. Circulating levels of IGF-1; H-FABP, and ETP were estimated using the corresponding ELISA kits. RESULTS: No statistical difference in the body mass index was detected between the healthy and control groups, while the mean age of infected patients was significantly higher (P = 0.0162) than the control. Patients generally showed elevated levels of inflammatory markers including CRP and ESR concomitant with elevated serum ferritin; D dimer and procalcitonin levels, besides the COVID-19 characteristic lymphopenia and hypoxemia were also frequent. Logistic regression analysis revealed that oxygen saturation; serum IGF-1, and H-FABP can significantly predict the infection progression (P < 0.001 each). Both serum IGF-1 and H-FABP as well as O2 saturation showed remarkable prognostic potentials in terms of large AUC values, high sensitivity/specificity values, and wide confidence interval. The calculated threshold for severity prognosis was 25.5 ng/mL; 19.5 ng/mL, 94.5, % and for IGF-1, H-FABP, and O2 saturation; respectively. The calculated thresholds of serum IGF-1; H-FABP, and O2 saturation showed positive and negative value ranges of 79-91% and 72-97%; respectively, with 66-95%, 83-94% sensitivity, and specificity; respectively. CONCLUSION: The calculated cut-off values of serum IGF-1 and H-FABP represent a promising non-invasive prognostic tool that would facilitate the risk stratification in COVID-19 patients, and control the morbidity/mortality associated with progressive infection.

FABP3, FABP4, and heart rate variability among patients with chronic schizophrenia.

Introduction: The prevalence of cardiovascular disease (CVD) and CVD-related deaths in patients with schizophrenia is high. An elevated risk of CVD has been associated with low heart rate variability (HRV). There is increasing evidence that fatty acid-binding protein (FABP)3 and FABP4 play roles in the development and progression of CVD. This study aimed to explore the association of circulating FABP3/FABP4 levels with HRV in patients with chronic schizophrenia. Methods: We included 265 consecutive patients with chronic schizophrenia who attended a disease management program. We used an enzyme-linked immunosorbent assay for the measurement of plasma concentrations of FABP3 and FABP4. Standard HRV was recorded at baseline following a standard protocol. Mean high- and low-frequency (HF/LF) HRV values were analyzed by tertile of FABP3 and FABP4 using one-way analysis of variance, and linear regression analysis was performed to assess trends. Results: A positive association between FABP3 and creatinine was found in multiple regression analysis. In addition, negative associations between levels of hematocrit, hemoglobin, HF HRV, and estimated glomerular filtration rate (eGFR) with FABP3 were also found. Moreover, positive associations between FABP4 with body mass index, diabetes mellitus, hypertension, systolic blood pressure, low-density lipoprotein-cholesterol, triglycerides, creatinine, and FABP3 were found. Furthermore, negative associations between levels of high-density lipoprotein-cholesterol, eGFR, and HF HRV with FABP4 were found. We also found a significant inverse association between FABP3 and HF HRV (p for trend = 0.008), and significant inverse associations between FABP4 with HF and LF HRV (p for trend = 0.007 and 0.017, respectively). Discussion: Together, this suggests that elevated levels of FABP3 and FABP4 may be linked to health problems related to CVD in patients with chronic schizophrenia.

An integrated microfluidic electrochemiluminescence device for point-of-care testing of acute myocardial infarction.

Heart-type fatty acid binding protein (H-FABP) is an early biomarker for acute myocardial infarction. The concentration of H-FABP in circulation sharply increases during myocardial injury. Therefore, fast and accurate detection of H-FABP is of vital significance. In this study, we developed an electrochemiluminescence device integrated with microfluidic chip (designed as m-ECL device) for on-site detection of H-FABP. The m-ECL device is consisted of a microfluidic chip that enable easy liquid handling as well as an integrated electronic system for voltage supply and photon detection. A sandwich-type ECL immunoassay strategy was employed for H-FABP detection by using Ru (bpy)32+ loaded mesoporous silica nanoparticles as ECL probes. This device can directly detect H-FABP in human serum without any pre-treatment, with a wide linear range of 1-100 ng/mL and a low limit of detection of 0.72 ng/mL. The clinical usability of this device was evaluated using clinical serum samples from patients. The results obtained from m-ECL device are well matched with those obtained from ELISA assays. We believe this m-ECL device has extensive application prospects for point-of-care testing of acute myocardial infarction.

Amelioration of Nicotine-Induced Conditioned Place Preference Behaviors in Mice by an FABP3 Inhibitor.

We previously demonstrated that fatty acid-binding protein 3 null (FABP3-/-) mice exhibit resistance to nicotine-induced conditioned place preference (CPP). Here, we confirm that the FABP3 inhibitor, MF1 ((4-(2-(1-(2-chlorophenyl)-5-phenyl-1H-pyrazol-3-yl)phenoxy) butanoic acid), successfully reduces nicotine-induced CPP scores in mice. MF1 (0.3 or 1.0 mg/kg) was orally administered 30 min before nicotine, and CPP scores were assessed in the conditioning, withdrawal, and relapse phases. MF1 treatment decreased CPP scores in a dose-dependent manner. Failure of CPP induction by MF1 (1.0 mg/kg, p.o.) was associated with the inhibition of both CaMKII and ERK activation in the nucleus accumbens (NAc) and hippocampal CA1 regions. MF1 treatment reduced nicotine-induced increases in phosphorylated CaMKII and cAMP-response element-binding protein (CREB)-positive cells. Importantly, the increase in dopamine D2 receptor (D2R) levels following chronic nicotine exposure was inhibited by MF1 treatment. Moreover, the quinpirole (QNP)-induced increase in the level of CaMKII and ERK phosphorylation was significantly inhibited by MF1 treatment of cultured NAc slices from wild type (WT) mice; however, QNP treatment had no effect on CaMKII and ERK phosphorylation levels in the NAc of D2R null mice. Taken together, these results show that MF1 treatment suppressed D2R/FABP3 signaling, thereby preventing nicotine-induced CPP induction. Hence, MF1 can be used as a novel drug to block addiction to nicotine and other drugs by inhibiting the dopaminergic system.

Novel FABP3 ligand, HY-11-9, ameliorates neuropathological deficits in MPTP-induced Parkinsonism in mice.

Parkinson's disease (PD) is characterized by dopaminergic (DAergic) neuronal loss in the substantia nigra pars compacta (SNpc), resulting from α-synuclein (αSyn) toxicity. We previously reported that αSyn oligomerization and toxicity are regulated by the fatty-acid binding protein 3 (FABP3), and the therapeutic effects of the FABP3 ligand, MF1, was successfully demonstrated in PD models. Here, we developed a novel and potent ligand, HY-11-9, which has a higher affinity for FABP3 (Kd = 11.7 ± 8.8) than MF1 (Kd = 302.8 ± 130.3). We also investigated whether the FABP3 ligand can ameliorate neuropathological deterioration after the onset of disease in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinsonism. Motor deficits were observed two weeks after MPTP treatment. Notably, oral administration of HY-11-9 (0.03 mg/kg) improved motor deficits in both beam-walking and rotarod tasks, whereas MF1 failed to improve the motor deficits in both tasks. Consistent with the behavioral tasks, HY-11-9 recovered dopamine neurons from MPTP toxicity in the substantia nigra and ventral tegmental areas. Furthermore, HY-11-9 reduced the accumulation of phosphorylated-serine129-α-synuclein (pS129-αSyn) and colocalization with FABP3 in tyrosine hydroxylase (TH)-positive DA neurons in the PD mouse model. Overall, HY-11-9 significantly improved MPTP-induced behavioral and neuropathological deterioration, suggesting that it may be a potential candidate for PD therapy.

Heart-Type Fatty Acid Binding Protein Binds Long-Chain Acylcarnitines and Protects against Lipotoxicity.

Heart-type fatty-acid binding protein (FABP3) is an essential cytosolic lipid transport protein found in cardiomyocytes. FABP3 binds fatty acids (FAs) reversibly and with high affinity. Acylcarnitines (ACs) are an esterified form of FAs that play an important role in cellular energy metabolism. However, an increased concentration of ACs can exert detrimental effects on cardiac mitochondria and lead to severe cardiac damage. In the present study, we evaluated the ability of FABP3 to bind long-chain ACs (LCACs) and protect cells from their harmful effects. We characterized the novel binding mechanism between FABP3 and LCACs by a cytotoxicity assay, nuclear magnetic resonance, and isothermal titration calorimetry. Our data demonstrate that FABP3 is capable of binding both FAs and LCACs as well as decreasing the cytotoxicity of LCACs. Our findings reveal that LCACs and FAs compete for the binding site of FABP3. Thus, the protective mechanism of FABP3 is found to be concentration dependent.