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.

Ameliorating effect of rutin against diclofenac-induced cardiac injury in rats with underlying function of FABP3, MYL3, and ANP.

Diclofenac is a widely prescribed anti-inflammatory drug having cardiovascular complications as one of the main liabilities that restrict its therapeutic use. We aimed to investigate for any role of rutin against diclofenac-induced cardiac injury with underlying mechanisms as there is no such precedent to date. The effect of rutin (10 and 20 mg/kg) was evaluated upon concomitant oral administration for fifteen days with diclofenac (10 mg/kg). Rutin significantly attenuated diclofenac-induced alterations in the serum cardiac markers (LDH, CK-MB, and SGOT), serum cytokine levels (TNF-α and IL-6), and oxidative stress markers (MDA and GSH) in the cardiac tissue. Histopathological examination and Scanning Electron Microscopy (SEM) findings displayed a marked effect of rutin to prevent diclofenac-mediated cardiac injury. Altered protein expression of myocardial injury markers (cTnT, FABP3, and ANP) and apoptotic markers (Bcl-2 and Caspase-3) in the cardiac tissue upon diclofenac treatment was considerably shielded by rutin treatment. MYL3 was unaffected due to diclofenac or rutin treatment. Rutin also significantly improved diclofenac-induced gastrointestinal and hepatic alterations based on the observed ameliorative effects in key mediators, oxidative stress markers, histopathology examination, and SEM findings. Overall results suggest that rutin can protect the diclofenac-induced cardiac injury by lowering oxidative stress, inhibiting inflammation, and reducing apoptosis. Further research work directs toward the development of phytotherapeutics for cardioprotection.

Differential Impact of Biologic Therapy on Heart Function Biomarkers in Rheumatoid Arthritis Patients: Observational Study on Etanercept, Adalimumab, and Tocilizumab.

BACKGROUND: Rheumatoid arthritis (RA) represents the most frequent form of inflammatory arthritis, affecting approximately 1% of the population worldwide. The introduction of novel therapeutic strategies targeting proinflammatory cytokines (TNF-α and interleukin-6) revolutionized the treatment of RA. This kind of treatment, although effective in a substantial portion of patients, may potentially cause many side effects. Among them, cardiovascular safety is one of the main concerns. OBJECTIVES: In the present study, we investigated the impact of treatment with anti-TNF-α and anti-IL-6 agents on heart function and levels of heart function biomarkers. METHODS: To measure this, we used cardiac function biomarkers, such as NT-pro Brain Natriuretic Peptide, mid regional pro-Atrial Natriuretic Peptide, Galectin-3, and Heart-Type Fatty Acid-Binding Protein and compared them to patients treated with methotrexate as well as healthy controls. RESULTS: Patients treated with biologics were characterized by low disease activity or were in remission. The disease activity in these groups was significantly lower than in the methotrexate group. All patients recruited for the study were characterized by normal heart function measured using echocardiography (EF>50%). With the exception of MR-proANP between tocilizumab and adalimumab (median: 1.01 vs. 0.49 nmol/L, p<0.05), we failed to observe any significant differences in biomarkers levels between groups treated with biologics. Contrary to this, patients on MTX showed higher NT-proBNP levels compared to adalimumab and healthy controls (p<0.05 for both). Striking differences have been shown in regard to H-FABP. The levels of these biomarkers were elevated in all biologics and the methotrexate group compared to healthy controls. CONCLUSION: As this biomarker reflects potential heart injury, we suggest that heart damage proceeds in a continuous manner in RA patients despite effective treatment and attainment of remission/low disease activity. This finding, however, should be verified in a larger cohort of RA patients to ascertain if the routine assessment of H-FABP may be useful for the detection of patients with RA who are at risk of development of heart damage.

Development of a Point-of-Care Test Based on Selenium Nanoparticles for Heart-Type Fatty Acid-Binding Proteins in Human Plasma and Blood.

Purpose: A rapid, convenient, cost-effective in-home test method for identifying heart-type fatty acid-binding protein (H-FABP) in plasma and blood by a lateral-flow immunoassay (LFIA) based on selenium nanoparticles (SeNPs) was developed. Methods: SeNPs were synthesized by using L-ascorbic acid to reduce seleninic acid at room temperature and conjugated with an anti-H-FABP monoclonal antibody. The limit of detection, specificity, and stability were measured, and clinical samples were analyzed. Results: The SeNPs were spherical with a diameter of 39.48 ± 3.72 nm and were conjugated successfully with an anti-H-FABP antibody, resulting in a total diameter of 46.52 ± 2.95 nm. The kit was designed for the determination of H-FABP in plasma specimens and whole blood specimens. The limit of detection was 1 ng/mL in plasma and blood, and the results could be determined within 10 min. No cross-reaction occurred with cardiac troponin I, creatine kinase-MB or myoglobin. The kits were stored at 40 °C for up to 30 days without significant loss of activity. The sensitivity was determined to be 100%, the specificity 96.67%, and the overall coincidence rate 97.83%. Conclusion: This SeNP assay kit can conveniently, rapidly, and sensitively detect H-FABP in plasma or blood with a readout of a simple color change visible to the naked eye with no special device, and can be used as an auxiliary means for the early screening of AMI. Clinical Trial Registration: Plasma and blood samples were used under approval from the Experimental Animal Ethics committee of the Joint National Laboratory for Antibody Drug Engineering, Henan University. The clinical trial registration number was HUSOM-2019-047.

Sterculia tragacantha Lindl Aqueous Leaf Extract Ameliorate Cardiomyopathy in Streptozotocin-induced Diabetic Rats via Urotensin II and FABP3 Expressions.

Sterculia tragacantha (ST) Lindl leaf is commonly used locally in the management of diabetes mellitus (DM) and its complications. This study was aimed at assessing the valuable effects of ST leaf on streptozotocin-diabetic cardiomyopathy (DCM). Streptozotocin was administered intraperitoneally to the experimental animals to induce DM, and hence, placed on different doses of ST for 14 days. Thereafter, on the 15th day of the experiment, the animals were euthanized, and a number of cardiomyopathy indices were investigated. The diabetic rats exhibited a momentous increase in hyperlipidemia, lipid peroxidation as well as a significant (p < 0.05) decline in antioxidant enzyme activities. The serum creatine kinase MB (CK-MB), C-reactive protein (CRP), cardiac troponin I, tumour necrosis factor-alpha (TNF-α) and urotensin II expression revealed a significant (p < 0.05) upsurge in diabetic rats. Also, the expression of GLUT4 and fatty acid-binding protein 3 (FABP3) were significantly (p < 0.05) reduced in diabetic rats. However, at the conclusion of the experimental trial ST significantly (p < 0.05) attenuated hyperlipidemia, oxidative stress biomarkers by augmenting the antioxidant enzyme activities and decrease in lipid peroxidation, ameliorated CK-MB, CRP, cardiac troponin I, TNF-α, and urotensin-II levels, and improved GLUT4 and FABP3 expressions. Similarly, the administration of ST prevented histological alterations in the heart of diabetic animals. Therefore, the obtained results suggest that ST could mitigate DCM in streptozotocin-induced diabetic rats.

Network pharmacology of bioactives from Sorghum bicolor with targets related to diabetes mellitus.

BACKGROUND: Sorghum bicolor (SB) is rich in protective phytoconstituents with health benefits and regarded as a promising source of natural anti-diabetic substance. However, its comprehensive bioactive compound(s) and mechanism(s) against type-2 diabetes mellitus (T2DM) have not been exposed. Hence, we implemented network pharmacology to identify its key compounds and mechanism(s) against T2DM. METHODS: Compounds in SB were explored through GC-MS and screened by Lipinski's rule. Genes associated with the selected compounds or T2DM were extracted from public databases, and the overlapping genes between SB-compound related genes and T2DM target genes were identified using Venn diagram. Then, the networking between selected compounds and overlapping genes was constructed, visualized, and analyzed by RStudio. Finally, affinity between compounds and genes was evaluated via molecular docking. RESULTS: GC-MS analysis of SB detected a total of 20 compounds which were accepted by the Lipinski's rule. A total number of 16 compounds-related genes and T2DM-related genes (4,763) were identified, and 81 overlapping genes between them were selected. Gene set enrichment analysis exhibited that the mechanisms of SB against T2DM were associated with 12 signaling pathways, and the key mechanism might be to control blood glucose level by activating PPAR signaling pathway. Furthermore, the highest affinities were noted between four main compounds and six genes (FABP3-Propyleneglyco monoleate, FABP4-25-Oxo-27-norcholesterol, NR1H3-Campesterol, PPARA-ß-sitosterol, PPARD-ß-sitosterol, and PPARG-ß-sitosterol). CONCLUSION: Our study overall suggests that the four key compounds detected in SB might ameliorate T2DM severity by activating the PPAR signaling pathway.

SERS-based magnetic immunoassay for simultaneous detection of cTnI and H-FABP using core-shell nanotags.

Acute myocardial infarction (AMI) is the single leading cause of worldwide mortality and morbidity. Heart-type fatty acid-binding protein (H-FABP) and cardiac troponin I (cTnI), as biomarkers emerging at different stages of AMI, have complementary advantages in terms of specificity and sensitivity. Therefore, we developed a magnetic immunoassay method based on surface-enhanced Raman scattering (SERS) to detect H-FABP and cTnI simultaneously. Herein, two mutually independent Raman reporter molecules were embedded between a gold core and silver shell and then combined with a tracer antibody to form a SERS immunoprobe. During detection, the SERS immunoprobe, target antigen and capture probe undergo an immune reaction to form a sandwich structure, and then the immune complex was enriched by a specific reaction of streptavidin on the surface of magnetic beads with biotin. Finally, the concentration of biomarkers was quantified by detecting the characteristic Raman peak intensities of the two Raman reporter molecules. Under the optimized conditions, the minimum detection limits of H-FABP and cTnI were 0.6396 and 0.0044 ng mL-1, respectively. Besides, the target antigen does not cross-react with non-specific proteins, showing good specificity. Therefore, our proposed SERS-based magnetic immunoassay method has the advantages of accuracy, rapidity and good selectivity, and has great potential for early diagnosis of acute myocardial infarction disease.

Identification of Fatty Acid Binding Protein 5 Inhibitors Through Similarity-Based Screening.

Fatty acid binding protein 5 (FABP5) is a promising target for development of inhibitors to help control pain and inflammation. In this work, computer-based docking (DOCK6 program) was employed to screen ∼2 M commercially available compounds to FABP5 based on an X-ray structure complexed with the small molecule inhibitor SBFI-26 previously identified by our group (also through virtual screening). The goal was discovery of additional chemotypes. The screen resulted in the purchase of 78 candidates, which led to the identification of a new inhibitor scaffold (STK-0) with micromolar affinity and apparent selectivity for FABP5 over FABP3. A second similarity-based screen resulted in three additional hits (STK-15, STK-21, STK-22) from which preliminary SAR could be derived. Notably, STK-15 showed comparable activity to the SBFI-26 reference under the same assay conditions (1.40 vs 0.86 µM). Additional molecular dynamics simulations, free energy calculations, and structural analysis (starting from DOCK-generated poses) revealed that R enantiomers (dihydropyrrole scaffold) of STK-15 and STK-22 have a more optimal composition of functional groups to facilitate additional H-bonds with Arg109 of FABP5. This observation suggests enantiomerically pure compounds could show enhanced activity. Overall, our study highlights the utility of using similarity-based screening methods to discover new inhibitor chemotypes, and the identified FABP5 hits provide a strong starting point for future efforts geared to improve activity.

Clinical Therapeutic Strategy and Neuronal Mechanism Underlying Post-Traumatic Stress Disorder (PTSD).

Post-traumatic stress disorder (PTSD) is characterized by an exaggerated response to contextual memory and impaired fear extinction, with or without mild cognitive impairment, learning deficits, and nightmares. PTSD is often developed by traumatic events, such as war, terrorist attack, natural calamities, etc. Clinical and animal studies suggest that aberrant susceptibility of emotion- and fear-related neurocircuits, including the amygdala, prefrontal cortex (PFC), and hippocampus may contribute to the development and retention of PTSD symptoms. Psychological and pharmacological therapy, such as cognitive behavioral therapy (CBT), and treatment with anti-depressive agents and/or antipsychotics significantly attenuate PTSD symptoms. However, more effective therapeutics are required for improvement of quality of life in PTSD patients. Previous studies have reported that ω3 long-chain polyunsaturated fatty acid (LCPUFA) supplements can suppress the development of PTSD symptoms. Fatty acid binding proteins (FABPs) are essential for LCPUFA intracellular trafficking. In this review, we have introduced Fabp3 null mice as an animal model of PTSD with impaired fear extinction. Moreover, we have addressed the neuronal circuits and novel therapeutic strategies for PTSD symptoms.

[Neurological mechanism and therapeutic strategy for posttraumatic stress disorders].

Posttraumatic stress disorder (PTSD) is most often induced by traumatic events and serious public health problems. PTSD is characterized by excessive response to contextual memory and impaired fear extinction and also associated with mild cognitive impairment, attention and learning deficits. Clinical and animal studies suggest that increased susceptibility of emotion- and fear-related neuronal circuits, including those in the amygdala, prefrontal cortex and hippocampus, contributes to development and retention of PTSD symptoms. However, mechanisms underlying this susceptibility to fear are not known and the useful therapeutic approaches are limited. Recently, there have been reports that ω3 LCPUFA supplementation can prevent development of PTSD and significantly ameliorate symptoms in patients with PTSD after accidental injury such as motor vehicle accidents and natural calamities. Importantly, Fabp7 null mice exhibit enhancement of fear memory consolidation and anxiety-related behaviors that resemble PTSD-like behaviors in humans. In this review, we focused behavioral phenotype of PTSD in Fabp3 null mice. The Fabp3 null mice exhibit cognitive deficits, hyperlocomotion and impaired fear extinction, and thus show PTSD-like behaviors. Chronic administration of ramelteon, a melatonin receptor agonist, improved all PTSD-like behaviors tested in Fabp3－/－ mice. Relevant to mechanisms underlying impaired fear extinction, we observed that Ca2＋/calmodulin-dependent protein kinase II (CaMKII) autophosphorylation increases in the basolateral amygdala (BLA) but remained unchanges in the hippocampus of Fabp3－/－ mice. Likewise, the number of c-Fos positive neurons in BLA significantly increased after exposure to contextual fear conditions. Finally, chronic ramelteon administration restored abnormal c-Fos expression and CaMKII autophosphorylation in the BLA of Fabp3－/－ mice. Taken together, Fabp3－/－ mice show PTSD-like behaviors, and ramelteon is an attractive candidate for PTSD therapeutics in human.

Effects of an immune stimulant, inactivated Mycobacterium phlei, on the growth performance as well as meat quality of fattening pigs.

Inactivated mycobacterium phlei (M. phlei) is well known for its immune-stimulatory functions in humans and livestock, but less information is available about the influence on meat quality of pigs when used as a feed additive. This study was designed to evaluate the effects of inactivated M. phlei on growth performance as well as meat quality of fattening pigs. A total of 240 cross-bred pigs ([Landrace × Yorkshire] × Duroc) with initial body weight of 80.14 ± 0.29 kg were randomly allocated to five treatments, each of which consisted of eight replicates with 6six pigs per replicate. The basal diet supplemented with five levels of inactivated M. phlei preparations (0, 3.5 × 109 [0.1% w/w], 7 × 109 [0.2%], 1.4 × 1010 [0.4%] or 2.1 × 1010 [0.6%] colony-forming units/kg) was respectively fed to the control group and four treatment groups for 30 days. Adding 0.4% of inactivated M. phlei to diet increased the average daily feed intake and average daily gain of pigs. Importantly, intramuscular fat percentage in the Longissimus dorsi (LD) was increased by feeding diet containing 0.2%, 0.4% and 0.6% of inactivated M. phlei, despite the pH value, drip loss, cooking loss and filter paper fluid uptake not being influenced. Analysis of the fatty acid components showed that some saturated fatty acids were decreased in LD after feeding inactivated M. phlei, but some monounsaturated fat acids (MUFAs) and polyunsaturated fatty acids were increased (PUFAs), which induced the total contents of MUFAs and PUFAs were improved. RT-PCR assay revealed that feeding inactivated M. phlei up-regulated genes implicated in fat metabolism in muscle, including ELOVL6, FASN, SCD1 and H-FABP. This study revealed that feeding inactivated M. phlei not only increased growth performance of fattening pigs, but also improved the meat quality by increasing intramuscular fat content, thus inactivated M. phlei probably has high utilization value in modern pig production.

trans-10,cis-12-Conjugated Linoleic Acid Affects Expression of Lipogenic Genes in Mammary Glands of Lactating Dairy Goats.

The molecular mechanisms on milk fat depression (MFD) in response to trans-10,cis-12-conjugated linoleic acid (t10,c12-CLA) supplementation in ruminants were elucidated in this research with dairy goats. A total of 30 2-year-old Xinong Saanen dairy goats [40 ± 5 days in milk (DIM)] at peak lactation stage were assigned to a 3 × 3 Latin square design (14 day treatment period, followed with 14 day washout). Three CLA treatments included (a) control, fed the basal diet only without CLA supplementation; (b) orally supplemented with 8 g/day of lipid-encapsulated CLA (low dose, CLA-1); and (c) orally supplemented with 16 g/day of lipid-encapsulated CLA (high dose, CLA-2). Expression levels of fatty acid metabolism genes in the mammary tissues were analyzed by real-time quantitative polymerase chain reaction (RT-qPCR) in three goats on day 1 and the other three goats on day 14 in each group after the discontinuation of CLA treatment in the third experimental period. Dietary supplementation of CLA led to a significant decrease of milk fat compared to the control (p < 0.05). Milk fat concentrations in CLA-1 and CLA-2 groups were 2.74 and 2.42%, respectively, while the milk fat concentration in the control group was 2.99%. Decreases in short- and medium-chain fatty acids (<16 carbons) and increases in unsaturated fatty acids were observed in the CLA-2 group (p < 0.05). The desaturation indexes of C16 and C18 fatty acids were obviously increased (p < 0.01). RT-qPCR results revealed decreases of the mRNA expression levels of SREBF1, PPARG, LPL, CD36, FABP3, ACSL1, FASN, ACACA, DGAT2, TIP47, ADRP, and BTN1A1 genes in mammary glands (p < 0.05) and an increase of the SCD gene because of CLA supplementation (p < 0.05). In conclusion, t10,c12-CLA-induced MFD was possibly the result from the downregulation of genes involved in lipogenesis in goat mammary glands.

FABP3 and brown adipocyte-characteristic mitochondrial fatty acid oxidation enzymes are induced in beige cells in a different pathway from UCP1.

Cold exposure and ß3-adrenergic receptor agonist (CL316,243) treatment induce the production of beige cells, which express brown adipocytes(BA)-specific UCP1 protein, in white adipose tissue (WAT). It remains unclear whether the beige cells, which have different gene expression patterns from BA, express BA-characteristic fatty acid oxidation (FAO) proteins. Here we found that 5 day cold exposure and CL316,243 treatment of WAT, but not CL316,243 treatment of primary adipocytes of C57BL/6J mice, increased mRNA levels of BA-characteristic FAO proteins. These results suggest that BA-characteristic FAO proteins are induced in beige cells in a different pathway from UCP1.

Heart-type fatty acid-binding protein as a potential biomarker of acute carbon monoxide poisoning.

BACKGROUND: The aim of this study was to investigate the role of serum heart-type fatty acid-binding protein (H-FABP) in the evaluation of patients with carbon monoxide (CO) poisoning. METHODS: Forty patients with acute CO poisoning admitted to the emergency department and 15 healthy adults as the control group were included in the study. Serum H-FABP levels of patients were studied on admission and at the 6th, 12th, and 18th hours. Patients were divided into 3 groups according to clinical severity as mild, moderate, and severe. Patients were also divided into 2 groups according to treatment with hyperbaric oxygen (HBO) or normobaric oxygen. RESULTS: Serum H-FABP levels of the patients were higher than those of the control group. There was a negative correlation between H-FABP levels and Glasgow Coma Scale score on admission. Heart-type fatty acid-binding protein levels were significantly higher in patients in the severe compared with mild group. Heart-type fatty acid-binding protein levels in patients treated with HBO were significantly higher than in those treated with normobaric oxygen. The cutoff value of serum H-FABP as an indicator for HBO treatment was determined as 1.5 ng/mL or higher, with a sensitivity of 85.7% and specificity of 69.7%. Serial measurement revealed that H-FABP level peaked at the sixth hour and reduced over time but remained higher than in the control group at the 18th hour. CONCLUSION: Heart-type fatty acid-binding protein may be a promising novel biomarker in the evaluation of clinical severity and in the selection of patients for HBO therapy in acute CO poisoning.

Dingxin recipe ( ) prevents ischemia/reperfusion-induced arrhythmias via up-regulating prohibitin and suppressing inflammatory responses.

OBJECTIVE: To identify the underlying mechanisms of the protective effects of Dingxin Recipe (: , DXR), a Chinese compound prescription that has been used clinically in China for more than 20 years, on ischemia/reperfusion (I/R)-induced arrhythmias in rat model. METHODS: A total of 30 rats were randomly divided into three groups: sham group, I/R group, and DXR-pretreated I/R (DXR-I/R) group. Rats in the DXR-DXRI/R group were intragastrically administrated with DXR (12.5 g/kg per day) for consecutive 7 days, while rats I/in the sham and I/R groups were administrated with normal saline. Arrhythmias were introduced by I/R and electrocardiograms (ECG) were recorded. Two-dimensional (2-D) polyacrylamide gel electrophoresis and matrix-matrix assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) were used to identify assisted differentially expressed proteins. Immunohistochemistry, real-time quantitative polymerase chain reaction (RQ-RQPCR), Western blot, and enzyme-linked immunosorbent assay (ELISA) were performed to analyze proteins PCR), obtained in the above experiments. RESULTS: DXR significantly reduced the incidence and mean duration of ventricular tachycardia and ventricular fibrillation and dramatically decreased the mortality, as well as arrhythmia score, compared with those of the I/R group. Among successfully identified proteins, prohibitin (PHB) and heart fatty acid binding protein (hFABP) were up-regulated in DXR-pretreated I/R rats compared with those of the I/R rats. In addition, compared with the I/R group, the level of glutathione (GSH) was elevated accompanied by reduced expressions of interleukin-6 (IL-6) and neutrophil infiltration in I/R rats with DXR pretreatment. CONCLUSIONS: DXR could alleviate I/R-induced arrhythmias, which might be related to increased expression of PHB. The enhanced expression of PHB prevented against the depletion of GSH and consequently inhibited apoptosis of cardiomyocytes. Furthermore, up-regulation of PHB might ameliorate I/R-induced cell death and leakage of hFABP by suppressing neutrophil infiltration and IL-6 expressions.

Effect of maternal micronutrients (folic acid, vitamin B12) and omega 3 fatty acids on liver fatty acid desaturases and transport proteins in Wistar rats.

A disturbed fatty acid metabolism increases the risk of adult non-communicable diseases. This study examines the effect of maternal micronutrients on the fatty acid composition, desaturase activity, mRNA levels of fatty acid desaturases and transport proteins in the liver. Pregnant female rats were divided into 6 groups at 2 levels of folic acid both in the presence and absence of vitamin B(12). The vitamin B(12) deficient groups were supplemented with omega 3 fatty acid. An imbalance of maternal micronutrients reduces liver docosahexaenoic acid, increases Δ5 desaturase activity but decreases mRNA levels, decreases Δ6 desaturase activity but not mRNA levels as compared to control. mRNA level of Δ5 desaturase reverts back to the levels of the control group as a result of omega 3 fatty acid supplementation. Our data for the first time indicates that maternal micronutrients differentially alter the activity and expression of fatty acid desaturases in the liver.

Dingxin recipe ( ) prevents ischemia/reperfusion-induced arrhythmias via up-regulating prohibitin and suppressing inflammatory responses / 中国结合医学杂志

<p><b>OBJECTIVE</b>To identify the underlying mechanisms of the protective effects of Dingxin Recipe (: , DXR), a Chinese compound prescription that has been used clinically in China for more than 20 years, on ischemia/reperfusion (I/R)-induced arrhythmias in rat model.</p><p><b>METHODS</b>A total of 30 rats were randomly divided into three groups: sham group, I/R group, and DXR-pretreated I/R (DXR-I/R) group. Rats in the DXR-DXRI/R group were intragastrically administrated with DXR (12.5 g/kg per day) for consecutive 7 days, while rats I/in the sham and I/R groups were administrated with normal saline. Arrhythmias were introduced by I/R and electrocardiograms (ECG) were recorded. Two-dimensional (2-D) polyacrylamide gel electrophoresis and matrix-matrix assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) were used to identify assisted differentially expressed proteins. Immunohistochemistry, real-time quantitative polymerase chain reaction (RQ-RQPCR), Western blot, and enzyme-linked immunosorbent assay (ELISA) were performed to analyze proteins PCR), obtained in the above experiments.</p><p><b>RESULTS</b>DXR significantly reduced the incidence and mean duration of ventricular tachycardia and ventricular fibrillation and dramatically decreased the mortality, as well as arrhythmia score, compared with those of the I/R group. Among successfully identified proteins, prohibitin (PHB) and heart fatty acid binding protein (hFABP) were up-regulated in DXR-pretreated I/R rats compared with those of the I/R rats. In addition, compared with the I/R group, the level of glutathione (GSH) was elevated accompanied by reduced expressions of interleukin-6 (IL-6) and neutrophil infiltration in I/R rats with DXR pretreatment.</p><p><b>CONCLUSIONS</b>DXR could alleviate I/R-induced arrhythmias, which might be related to increased expression of PHB. The enhanced expression of PHB prevented against the depletion of GSH and consequently inhibited apoptosis of cardiomyocytes. Furthermore, up-regulation of PHB might ameliorate I/R-induced cell death and leakage of hFABP by suppressing neutrophil infiltration and IL-6 expressions.</p>

Discovery of highly selective inhibitors of human fatty acid binding protein 4 (FABP4) by virtual screening.

In this study, a series of small molecule inhibitors of human FABP4 were identified through virtual screening. Compound 1 is the most potent hit against FABP4 with a selectivity of more than 144-fold preferences over human FABP3. In addition, MD simulation and mutation studies revealed key residues for inhibitory potency and selectivity, which provides a guideline for further drug design against obesity, diabetes and atherosclerosis.

Circulating levels of heart-type fatty acid-binding protein in a general Japanese population: effects of age, gender, and physiologic characteristics.

BACKGROUND: Serum heart-type fatty acid-binding protein (H-FABP) has been widely used as a marker of cardiac myocyte injury. This study was carried out to examine the relationships of H-FABP levels with age, gender, and other physiologic characteristics in a large population of community-dwelling residents. METHODS AND RESULTS: Serum H-FABP levels were measured in 2,099 subjects who received an annual health check-up (age 40-87 years). The relationships between H-FABP and blood pressure, laboratory data, electrocardiogram (ECG) findings, and lifestyle factors were cross-sectionally analyzed. Mean H-FABP values were significantly higher in men than in women. Serum H-FABP levels were increased with aging significantly. Both the multivariate regression and multiple logistic regression analyses indicated that serum H-FABP levels were independently affected by age, body mass index, creatinine clearance, and ECG abnormality score. CONCLUSION: Serum H-FABP levels were affected by age, gender, obesity, renal function, and ECG abnormality in a large group of volunteers. These effects should be taken into account in determining appropriate reference values for H-FABP. In addition, high serum H-FABP levels may represent latent cardiac injury and have important clinical implications.

Activation of Stat5 and induction of a pregnancy-like mammary gland differentiation by eicosapentaenoic and docosapentaenoic omega-3 fatty acids.

The protective effect of early pregnancy against breast cancer can be attributed to the transition from undifferentiated cells in the nulliparous to the differentiated mature cells during pregnancy. Considerable evidence suggests strongly that the n-3 polyunsaturated fatty acid (PUFA) content of adipose breast tissue is inversely associated with an increased risk of breast cancer. Here, we report that there was a decrease in the n-6/n-3 PUFA ratio and a significant increase in concentration of n-3 PUFA docosapentaenoic acid and eicosapentaenoic acid in the pregnant gland. The functional role of n-3 PUFAs on differentiation was supported by the studies in the fat-1 transgenic mouse, which converts endogenous n-6 to n-3 PUFAs. Alternation of the n-6/n-3 ratio in favor of n-3 PUFA, and particularly docosapentaenoic acid, in the mammary gland of fat-1 mouse resulted in development of lobulo-alveolar-like structure and milk protein beta-casein expression, mimicking the differentiated state of the pregnant gland. Docosapentaenoic acid and eicosapentaenoic acid activated the Jak2/Stat5 signaling pathway and induced a functional differentiation with production of beta-casein. Expression of brain type fatty acid binding protein brain type fatty acid binding protein in virgin transgenic mice also resulted in a reduced ratio of n-6/n-3 PUFA, a robust increase in docosapentaenoic acid accumulation, and mammary differentiation. These data indicate a role of mammary derived growth inhibitor related gene for preferential accumulation of n-3 docosapentaenoic acid and eicosapentaenoic acid in the differentiated gland during pregnancy. Thus, alternation of n-6/n-3 fatty acid compositional ratio in favor of n-3 PUFA, and particularly docosapentaenoic acid and eicosapentaenoic acid, is one of the underlying mechanisms of pregnancy-induced mammary differentiation.