Anti-Freezing and Ultrasensitive Zwitterionic Betaine Hydrogel-Based Strain Sensor for Motion Monitoring and Human-Machine Interaction.

Ultrasensitive and reliable conductive hydrogels are significant in the construction of human-machine twinning systems. However, in extremely cold environments, freezing severely limits the application of hydrogel-based sensors. Herein, building on biomimetics, a zwitterionic hydrogel was elaborated for human-machine interaction employing multichemical bonding synergies and experimental signal analyses. The covalent bonds, hydrogen bonds, and electrostatic interactions construct a dense double network structure favorable for stress dispersion and hydrogen bond regeneration. In particular, zwitterions and ionic conductors maintained excellent strain response (99 ms) and electrical sensitivity (gauge factor = 14.52) in the dense hydrogel structure while immobilizing water molecules to enhance the weather resistance (-68 °C). Inspired by the high sensitivity, zwitterionic hydrogel-based strain sensors and remote-control gloves were designed by analyzing the experimental signals, demonstrating promising potential applications within specialized flexible materials and human-machine symbiotic systems.

Sacubitril/Valsartan Can Reduce Atrial Fibrillation Recurrence After Catheter Ablation in Patients with Persistent Atrial Fibrillation.

PURPOSE: This study compared the effectiveness of sacubitril/valsartan (SV) vs. valsartan (V) for treating persistent atrial fibrillation (AF) after radio-frequency catheter ablation (RFCA). METHODS: Patients with persistent AF who received RFCA were randomly assigned to the SV or V treatment group with the intervention lasting for 12 months. The primary outcome included any atrial arrhythmia episode lasting ≥ 30 s after a 3-month blanking period. The secondary outcome included any atrial arrhythmia episode lasting ≥ 24 h or requiring cardioversion after a 3-month blanking period. The H2FPEF score was used to assess the possibility of patients suffering from heart failure with preserved ejection fraction. RESULTS: A total of 143 patients with persistent AF who received RFCA were randomized for the study, with 5 patients failing to follow-up. Among them, 29 (42%) out of 69 patients receiving V and 15 (21.7%) out of 69 patients receiving SV reached the primary endpoint (P < 0.001). A total of 26 (37.7%) out of 69 patients receiving V and 7 (10.1%) out of 69 patients receiving SV reached the secondary endpoint (P < 0.001). A decrease in the H2FPEF score after a 1-year follow-up seemed to be related to the recurrence of AF (OR, 0.065; 95% CI: 0.018-0.238, P < 0.001). CONCLUSIONS: SV can decrease AF recurrence after catheter ablation in patients with persistent AF at the 1-year follow-up. The mechanism for this process may be related to the reduction in the H2FPEF score in patients with preserved ejection fraction heart failure.

Spinal Cord Stimulation Attenuates Neural Remodeling, Inflammation, and Fibrosis After Myocardial Infarction.

OBJECTIVES: Spinal cord stimulation (SCS) is an established neuromodulation method that regulates the cardiac autonomic system. However, the biological mechanisms of the therapeutic effects of SCS after myocardial infarction (MI) remain unclear. MATERIALS AND METHODS: Twenty-five rabbits were divided into five groups: SCS-MI (voltage: 0.5 v; pulse width: 0.2 ms; 50 Hz; ten minutes on and 30 minutes off; two weeks; n = 5), MI (n = 5), sham SCS-MI (voltage: 0 v; two weeks; n = 5), sham MI (n = 5), and blank control (n = 5) groups. MI was induced by permanent left anterior descending artery ligation. SCS-MI and sham SCS-MI rabbits received the corresponding interventions 24 hours after MI. Autonomic remodeling was evaluated using enzyme-linked immunosorbent assay and immunohistochemistry. Inflammation and myocardial fibrosis were assessed using immunohistochemistry, quantitative polymerase chain reaction, hematoxylin and eosin staining, Masson staining, and Western blot. RESULTS: SCS improved the abnormal systemic autonomic activity. Cardiac norepinephrine decreased after MI (p < 0.01) and did not improve with SCS. Cardiac acetylcholine increased with SCS compared with the MI group (p < 0.05). However, no difference was observed between the MI and blank control groups. Growth-associated protein 43 (p < 0.001) and tyrosine hydroxylase (p < 0.001) increased whereas choline acetyltransferase (p < 0.05) decreased in the MI group compared with the blank control group. These changes were attenuated with SCS. SCS inhibited inflammation, decreased the ratio of phosphorylated-Erk to Erk (p < 0.001), and increased the ratio of phosphorylated-STAT3 to STAT3 (p < 0.001) compared with the MI group. Myocardial fibrosis was also attenuated by SCS. CONCLUSIONS: SCS improved abnormal autonomic activity after MI, leading to reduced inflammation, reactivation of STAT3, and inhibition of Erk. Additionally, SCS attenuated myocardial fibrosis. Our results warrant future studies of biological mechanisms of the therapeutic effects of SCS after MI.

Matr3 reshapes m6A modification complex to alleviate macrophage inflammation during atherosclerosis.

Atherosclerosis, characterized as the chronic inflammation of the arterial wall, is one of the leading causes of coronary artery disease (CAD), and macrophages are found to play essential roles in the initiation and progression of inflammation in atherosclerosis. N6-methyladenosine (m6A) modification, as the most abundant epi-transcriptomic modification in mRNA, is found to mediate the atherogenic inflammatory cascades in vascular endothelium. The detailed molecular mechanism of m6A methylation regulating inflammatory response during atherosclerosis is still not fully known. In this study, we find oxidized low-density lipoprotein (oxLDL) stimulation increases methyltransferases Mettl3 and Mettl14 expressions in macrophages, whereas the total m6A modification level in macrophages decreases under oxLDL stimulation. Matrin-3 (Matr3), an RNA binding protein, is identified to play a suppressive role on oxLDL-mediated macrophage inflammatory responses through inhibiting activation of pro-inflammatory signaling, mitogen-activated protein kinase (Mapk) by m6A-mediated mRNA decay via regulating the formation of Mettl3-Mettl14 complex. Moreover, we find that Matr3 expression decreases in the oxLDL-stimulated macrophages, and the peripheral blood-derived monocytes from patients with CAD, and overexpression of Matr3 significantly alleviates atherosclerosis development in vivo. Our study for the first time clarifies the role of Matr3 on macrophage inflammatory responses during atherosclerotic development, and supplies deep understanding on the relationship of m6A modification and inflammatory responses in atherosclerosis.

Effects of physicochemical and structural properties of single and double feedstuffs derived from different botanic sources on in vitro starch digestion and glucose release kinetics.

Starch is the largest constituent in animal diets. The aims of this study were as follows: (a) to assess the variability of basic physicochemical properties and in vitro starch digestion of starchy feedstuffs and investigate relationship between physicochemical properties and starch digestion of the feedstuffs, and (b) to explore the effects of different sources of starchy feedstuffs on starch digestion and glucose release. In this study, we determined the inherent molecular structure and granular structure of starch and chemical compositions of seven starchy feedstuffs, as well as starch digestion in single feedstuff and different feedstuffs combined with corn. Scanning electron microscope (SEM) results revealed significant difference between granule shape and size of starch of different feedstuffs. Fourier transforms infrared (FTIR) spectra for barley and wheat had lower (p < 0.05) absorbance band at areas A_860 and A_928 than other feedstuffs, yet rice starch had the lowest value for ratio (R) (1047/1022). Moreover, digestion rate ranged from 0.0157/min for resistant starch (sorghum) to 0.029/min for rapidly starch (broken rice). The principle component analysis (PCA) showed that predicted glycaemic index (pGI) was positively related to A_1022, glucose and rapidly (RDS) content and negatively related to A_995, A_1047, R (1047/1022), resistant starch (RS) and amylose content. Most of the feedstufss with corn combination had no effect on rate of starch digestion. In addition, different starchy feeds and corn combination changed the rate of starch digestion, when barley, however, sorghum combined with corn seemed to affect rate of starch digestion. To sum up, different sources differed in basic physicochemical and structural properties, which would influence the digestion rate of starch and the release of glucose. Combination of different feedstuffs particular sorghum with corn has interactive effect on starch digestion and the release of glucose.

Dietary protein degradability effect on performance of lambs experimentally infected with Haemonchus contortus and Trichostrongylus colubriformis.

The study investigated the effects of dietary protein degradation rate on growth performance and immune response of crossbred Dorper × short-tail Han ram lambs experimentally infected with Haemonchus contortus and Trichostrongylus colubriformis. Eighteen lambs were randomly assigned to three dietary treatments, rapidly degradable protein (RDP), moderately degradable protein (MDP), and slowly degradable protein (SDP) diets. Feed intake and body weight of the lambs were recorded weekly until 42 days post-infection. The fecal egg count (FEC), FAMACHA scores, and immunoglobulins (IgG, IgM and IgA) were also monitored during the experimental period. A metabolic trial was conducted to assess apparent digestibility and volatile fatty acids were also determined. The lambs in SDP and MDP groups had higher feed, nutrient intake, weight gain, and feed efficiency than those in the RDP group. Feed conversion ratio (FCR) of the lambs in RDP group was higher than those in the SDP and MDP groups. A significant (P < 0.001) decrease in FEC was observed in the SDP and MDP groups. Dietary treatment had no significant effect on FAMACHA scores and concentration of serum antibodies. Concentration of acetic acid was higher (P < 0.013) in the lambs fed RDP than those fed the SDP and MDP diets. The lambs fed SDP diet had higher apparent digestibility than those fed the RDP diet. The poor performances in RDP group could be overcome by including SDP that ensures adequate post-ruminal protein supply reaching the small intestine.

Distinct origins and functions of cardiac orthotopic macrophages.

Macrophages are one cell type in the innate immune system. Recent studies involving macrophages have overturned the conventional concept that circulating bone marrow-derived blood mononuclear cells in the adult body continuously replace macrophages residing in the tissues. Investigations using refined technologies have suggested that embryonic hematopoiesis can result in the differentiation into macrophage subgroups in some tissues. In adulthood, these macrophages are self-sustaining via in situ proliferation, with little contribution of circulating bone marrow-derived blood mononuclear cells. Macrophages are integral component of the heart, accounting for 8% of the non-cardiac cells. The use of innovative molecular techniques in paradigm shifting researches has revealed the complexity of cardiac macrophages, including their heterogeneity and ontological diversity. Resident cardiac macrophages modulate the physiological and pathophysiological processes of the cardiovascular system, with distinct and crucial roles in healthy and injured hearts. Their functions include sensing of pathogens, antigen presentation, digesting cell debris, regulating inflammatory responses, generating distinct cytokines, and secreting some regulatory factors. More recent studies have revealed further functions of cardiac macrophages. This review focuses on macrophages within the cardiovascular system. We discuss evidence that has changed our collective view of cardiac macrophage subgroups, and improved our understanding of the different phenotypes, cell surface markers, heterogeneities, origins, developments, and the dynamic and separate roles of these cardiac macrophage subgroups in the steady state and injured hearts. This review may provide novel insights concerning the pathophysiology of cardiac-resident macrophages in cardiovascular diseases and innovative therapeutic strategies that could include the modulation of the role of macrophages in cardiovascular injuries.

RNA helicase DDX5 participates in oxLDL-induced macrophage scavenger receptor 1 expression by suppressing mRNA degradation.

The DEAD box protein DDX5, an ATP-dependent RNA helicase, plays an important role in transcriptional regulation and is associated with solid tumors and leukemia. However, its role in oxLDL-induced lipid uptake in macrophages remains unclear. In this study, we detected the expression of DDX5 mRNA and protein in oxidized low-density lipoprotein (oxLDL)-treated human primary macrophages that were induced from monocytes isolated from human peripheral blood with or without several chemical inhibitors using quantitative real-time PCR (qRT-PCR) or Western blotting. We found that oxLDL induced DDX5 expression to be independent of both the MAPK and NF-κB pathways. We also found that DDX5 promoted macrophage lipid uptake by evaluating the fluorescence intensity of engulfed dil-oxLDL. Various scavenger receptors that participate in lipid uptake were detected in siR-DDX5 transfected macrophages using qRT-PCR and Western blotting. Macrophage scavenger receptor A (MSR1) was found to be involved the upregulation of DDX5-mediated lipid uptake. Through the use of a dual luciferase reporter assay system and incubation with cycloheximide (CHX) MG132 and actidione (ActD), we found that DDX5 promoted MSR1 protein expression by stabilizing MSR1 mRNA. Moreover, the mechanism involved in DDX5 regulation of MSR1 mRNA was also explored using mass spectrum analysis; Immunoprecipitations (IPs) and RNA- Immunoprecipitations (R-IPs) revealed that mettl3 was involved in DDX5-mediated MSR1 mRNA stabilization. In addition, we also demonstrated that DDX5 inhibited mettl3 to catalyze m6a methylation in MSR1 mRNA, which contributed to the maintenance of MSR1 mRNA stability. In conclusion, ox-LDL promotes DDX5 expression in macrophages, which interacts with mettl3 to stabilize MSR1 mRNA by decreasing the m6a modification of MSR1 mRNA, ultimately promoting lipid uptake in macrophages.

Cross-talk between macrophages and atrial myocytes in atrial fibrillation.

Increased macrophage accumulation occurs in the atria of patients with atrial fibrillation (AF). However, the phenotype and functions of the macrophages in AF remain unclear. We investigated the macrophage-atrial myocyte interaction in AF patients and found that the increased macrophages were mainly pro-inflammatory macrophages (iNOS+, Arg1-). Tachypacing of HL-1 atrial myocytes also led to pro-inflammatory macrophage polarization. In addition, lipopolysaccharide (LPS)-stimulated pro-inflammatory macrophages-induced atrial electrical remodeling, evidenced by increased AF incidence and decreased atrial effective refractory period and L-type calcium currents (I Ca-L) in both canine and mouse AF models. Depletion of macrophages relieved LPS-induced atrial electrical remodeling, confirming the role of pro-inflammatory macrophages in the pathogenesis of AF. We also found that the effect of LPS-stimulated macrophages on atrial myocytes was mediated by secretion of interleukin 1 beta (IL-1ß), which inhibited atrial myocyte quaking protein (QKI) expression. IL-1ß knockout in macrophages restored the LPS-stimulated macrophage-induced inhibition of QKI and CACNA1C (α1C subunit of L-type calcium channel) in atrial myocytes. Meanwhile, QKI overexpression in atrial myocytes restored the LPS-stimulated macrophage-induced electrical remodeling through enhanced binding of QKI to CACNA1C mRNA, which upregulated the expression of CACNA1C as well as I Ca-L. In contrast, QKI knockout inhibited CACNA1C expression. Finally, using transcription factor activation profiling plate array and chromatin immunoprecipitation, we revealed that special AT-rich sequence binding protein 1 activated QKI transcription. Taken together, our study uncovered the functional interaction between macrophages and atrial myocytes in AF. AF induced pro-inflammatory macrophage polarization while pro-inflammatory macrophages exacerbated atrial electrical remodeling by secreting IL-1ß, further inhibiting QKI expression in atrial myocytes, which contributed to I Ca-L downregulation. Our study demonstrates a novel molecular mechanism underlying the pathogenesis and progression of AF and suggests that QKI is a potential therapeutic target.

CD97/ADGRE5 Inhibits LPS Induced NF-κB Activation through PPAR-γ Upregulation in Macrophages.

CD97/ADGRE5 protein is predominantly expressed on leukocytes and belongs to the EGF-TM7 receptors family. It mediates granulocytes accumulation in the inflammatory tissues and is involved in firm adhesion of PMNC on activated endothelial cells. There have not been any studies exploring the role of CD97 in LPS induced NF-κB activation in macrophages. Therefore, we first measured the CD97 expression in LPS treated human primary macrophages and subsequently analyzed the levels of inflammatory factor TNF-α and transcription factor NF-κB in these macrophages that have been manipulated with either CD97 knockdown or overexpression. We found that a reported anti-inflammatory transcription factor, PPAR-γ, was involved in the CD97 mediated NF-κB suppression. Furthermore, by immunofluorescence staining, we established that CD97 overexpression not only inhibited LPS induced p65 expression in the nucleus but also promoted the PPAR-γ expression. Moreover, using CD97 knockout THP-1 cells, we further demonstrated that CD97 promoted PPAR-γ expression and decreased LPS induced NF-κB activation. In conclusion, CD97 plays a negative role in LPS induced NF-κB activation and TNF-α secretion, partly through PPAR-γ upregulation.

Relationship between Molecular Structure Characteristics of Feed Proteins and Protein In vitro Digestibility and Solubility.

The nutritional value of feed proteins and their utilization by livestock are related not only to the chemical composition but also to the structure of feed proteins, but few studies thus far have investigated the relationship between the structure of feed proteins and their solubility as well as digestibility in monogastric animals. To address this question we analyzed soybean meal, fish meal, corn distiller's dried grains with solubles, corn gluten meal, and feather meal by Fourier transform infrared (FTIR) spectroscopy to determine the protein molecular spectral band characteristics for amides I and II as well as α-helices and ß-sheets and their ratios. Protein solubility and in vitro digestibility were measured with the Kjeldahl method using 0.2% KOH solution and the pepsin-pancreatin two-step enzymatic method, respectively. We found that all measured spectral band intensities (height and area) of feed proteins were correlated with their the in vitro digestibility and solubility (p≤0.003); moreover, the relatively quantitative amounts of α-helices, random coils, and α-helix to ß-sheet ratio in protein secondary structures were positively correlated with protein in vitro digestibility and solubility (p≤0.004). On the other hand, the percentage of ß-sheet structures was negatively correlated with protein in vitro digestibility (p<0.001) and solubility (p = 0.002). These results demonstrate that the molecular structure characteristics of feed proteins are closely related to their in vitro digestibility at 28 h and solubility. Furthermore, the α-helix-to-ß-sheet ratio can be used to predict the nutritional value of feed proteins.

Interruption of CD40 Pathway Improves Efficacy of Transplanted Endothelial Progenitor Cells in Monocrotaline Induced Pulmonary Arterial Hypertension.

BACKGROUND/AIMS: Transplantation of endothelial progenitor cells (EPCs) plays a therapeutic role in pulmonary arterial hypertension (PAH). Meanwhile, recruitment of progenitors has potential inflammatory effects and exaggerates vascular injury. CD40 pathway is identified as a major player in vascular inflammatory events. In this study, we investigated the role of CD40 pathway in regulating early outgrowth EPC functions, and searched for improvements in PAH cell therapy. METHODS: EPCs were isolated from rat bone marrow and cultured for 7 days. After treatment with soluble CD40 ligand (sCD40L) for 24 hours, EPC migration, adhesion, proliferation, paracrine and vasculogenesis functions were tested. Rat PAH model was founded by subcutaneous injection of monocrotaline (MCT). Control EPCs or lentivirus vectors (Lv)-shRNA-CD40 EPCs were infused via tail vein at day 7, 14, and 21 after MCT injection. Therapeutic effects were evaluated at day 28. RESULTS: sCD40L dose-dependently impaired EPC migration, adhesion, proliferation, and vasculogenesis functions. However, paracrine effects of soluble intercellular adhesion molecule-1, vascular endothelial growth factor and interleukin-6 were dose-dependently improved by sCD40L. Control EPC-derived conditioned medium protected endothelial cell in vitro vasculogenesis, while sCD40L-pretreated ones showed detrimental effects. After MCT injection, sCD40L levels in rat serum increased gradually. Other than in vitro results, benefits of both two EPC treatments were obvious, even taken at day 21. Benefits of control EPCs wore off over time, but those of Lv-shRNA-CD40 EPCs were more effective and enduring, as characterized by both ameliorated rat hemodynamic and reversed vascular remodeling. Furthermore, Lv-shRNA-CD40 EPCs integrated into endothelium better, rather than into adventitia and media. CONCLUSION: sCD40L impaired protective effects of EPCs. Traditional EPC treatments were limited in PAH, while interruption of CD40 pathway of transplanted cells could apparently improve the therapeutic efficacy.

Wnt1 positively regulates CD36 expression via TCF4 and PPAR-γ in macrophages.

BACKGROUND: Scavenger receptors including CD36 control the phagocytosis of oxidized low-density lipoprotein and play an important role in macrophage physiology, but the underlying molecular mechanism by which CD36 is regulated in macrophages or during macrophage differentiation from monocytes remains to be determined. METHODS: Here, we investigated the relationship between Wnt1 and CD36 during macrophage differentiation. CD36 was suppressed following knockdown of Wnt1 by siRNA, while it was increased by ectopic overexpression of Wnt1 in macrophages. Using a ß-catenin inhibitor, peroxisome proliferator-activated receptor gamma (PPAR-γ) siRNA, and transcription factor 4 (TCF4) siRNA, we demonstrated that Wnt1 regulates the expression of CD36 through TCF4 and PPAR-γ. Co-immunoprecipitation, chromatin immunoprecipitation, and immunofluorescence experiments showed that ß-catenin interacted with PPAR-γ and that PPAR-γ and TCF4 colocalized in the nucleus. Furthermore, Pax3 regulated Wnt1 via binding to the first binding site in the Wnt1 promoter. RESULTS: Our study demonstrated that during macrophage differentiation from monocytes, Wnt1 promotes CD36 expression via activation of PPAR-γ and TCF4. CONCLUSIONS: Our findings suggest that Wnt1 plays an important role in macrophage physiology via activation of the canonical Wnt pathway.

miR-29a promotes scavenger receptor A expression by targeting QKI (quaking) during monocyte-macrophage differentiation.

Monocyte differentiation into macrophages results in upregulation of miR-29a and scavenger receptor A (SRA) expression, while the expression of RNA binding protein, QKI is suppressed. Since SRA is a functionally important protein in atherosclerosis, it is imperative to understand the various mechanisms involved in its regulation specially the mechanism involving miR-29a. There are individual studies linking miR-29a to SRA or QKI to monocyte differentiation but there is no evidence of any linkage among them. Therefore, we intend to investigate the association among these three, if any, in terms of regulation of SRA expression. Hence, in this study, the differentiated macrophages were initially transfected with miR-29a or its inhibitor and it was shown that QKI is a direct target of mir-29a. In addition, it was also observed by bioinformatics analysis that 3'UTR in SRA mRNA has QKI binding site. So, we attempted to further understand the role of QKI in SRA regulation. The macrophages were manipulated either with overexpression of QKI or by its ablation and it was observed that QKI suppressed SRA at the transcriptional level. Moreover, with the help of luciferase reporter vector, it was shown that QKI inhibited SRA transcription by binding to QRE region in its 3'UTR mRNA. Furthermore, to link the QKI mediated regulation of SRA expression with its functional activity; we analyzed lipid uptake capacity of macrophages transfected with either ectopic OKI plasmid or ablated for QKI. It was observed that, indeed, QKI upregulation inhibits lipid uptake by repressing SRA expression. Overall, our study demonstrates that miR-29a inhibits QKI, which in turn results in upregulation of SRA and lipid uptake.

Transient cardiac injury during H7N9 infection.

BACKGROUND: Recent reports have characterized virological and clinical features of the novel reassortant avian-origin influenza A (H7N9) virus. However, cardiovascular involvement during H7N9 infection is still unclear. In this study, we evaluate cardiac injury among H7N9-infected patients. MATERIALS AND METHODS: A total of 40 patients who were laboratory-confirmed with H7N9 infection were retrospectively included and grouped by Acute Physiology and Chronic Health Evaluation II (APACHE II) score into four subgroups I(0-10), II(11-20), III(21-30) and IV(31-71). Cardiovascular complications and markers of cardiac injury including creatinine kinase (CK), CK iso-enzyme (CK-MB), cardiac troponin I (cTNI) and brain natriuretic peptide (BNP) were assessed. Electrocardiogram (ECG) and echocardiography (ECHO) were also performed. RESULTS: Half of patients manifested with cardiovascular complications, with hypotension (47.5%) and heart failure (40.0%) the most prevalent. CK, CK-MB and cTNI showed marked increase with H7N9 virus infection but significantly decreased after H7N9 viral tests turned negative. More than half of patients presented with an abnormal ECG, but most of them are benign changes. ECHO examination showed different degree of impairment of cardiac function. Pulmonary artery systolic pressure was increased in all groups. Cardiac damage was more evident in patients with higher APACHE II score. CONCLUSIONS: H7N9 virus exerts a transient impairment on the cardiovascular system. Patients with a higher APACHE II score are more susceptible to cardiac damage.

Autophagy protects against senescence and apoptosis via the RAS-mitochondria in high-glucose-induced endothelial cells.

BACKGROUNDS: Autophagy is an important process in the pathogenesis of diabetes and plays a critical role in maintaining cellular homeostasis. However, the autophagic response and its mechanism in diabetic vascular endothelium remain unclear. METHODS AND RESULTS: We studied high-glucose-induced renin-angiotensin system (RAS)-mitochondrial damage and its effect on endothelial cells. With regard to therapeutics, we investigated the beneficial effect of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II type 1 receptor blockers (ARBs) against high-glucose-induced endothelial responses. High glucose activated RAS, enhanced mitochondrial damage and increased senescence, apoptosis and autophagic-responses in endothelial cells, and these effects were mimicked by using angiotensin II (Ang). The use of an ACEI or ARB, however, inhibited the negative effects of high glucose. Direct mitochondrial injury caused by carbonyl cyanide 3-chlorophenylhydrazone (CCCP) resulted in similar negative effects of high glucose or Ang and abrogated the protective effects of an ACEI or ARB. Additionally, by impairing autophagy, high-glucose-induced senescence and apoptosis were accelerated and the ACEI- or ARB-mediated beneficial effects were abolished. Furthermore, increases in FragEL™ DNA Fragmentation (TUNEL)-positive cells, ß-galactosidase activation and the expression of autophagic biomarkers were revealed in diabetic patients and rats, and the treatment with an ACEI or ARB decreased these responses. CONCLUSIONS: These data suggest that autophagy protects against senescence and apoptosis via RAS-mitochondria in high-glucose-induced endothelial cells.

Advances of research on glycinin and ß-conglycinin: a review of two major soybean allergenic proteins.

Being an important crop, soybean is widely used in the world and plays a vital role in human and animal nutrition. However, it contains several antinutritional factors (ANFs) including soybean agglutinin, soybean protease inhibitors, soybean allergenic proteins, etc., that may result in poor food utilization, decreased growth performance, and even disease. Among these ANFs, soybean allergenic proteins can lead to allergic reactions in human and animals, which has become a public problem all over the world, but our knowledge on it is still inadequate. This paper aims to provide an update on the characteristics, detection or exploration methods, and in vivo research models of soybean allergenic proteins; especially glycinin and ß-conglycinin are deeply discussed. Through this review, we may have a better understanding on the advances of research on these two soybean allergenic proteins. Besides, the ingredient processing used to reduce the allergenicity of soybean is also reviewed.

TRPV1 activation exacerbates hypoxia/reoxygenation-induced apoptosis in H9C2 cells via calcium overload and mitochondrial dysfunction.

Transient potential receptor vanilloid 1 (TRPV1) channels, which are expressed on sensory neurons, elicit cardioprotective effects during ischemia reperfusion injury by stimulating the release of neuropeptides, namely calcitonin gene-related peptide (CGRP) and substance P (SP). Recent studies show that TRPV1 channels are also expressed on cardiomyocytes and can exacerbate air pollutant-induced apoptosis. However, whether these channels present on cardiomyocytes directly modulate cell death and survival pathways during hypoxia/reoxygenation (H/R) injury remains unclear. In the present study, we investigated the role of TRPV1 in H/R induced apoptosis of H9C2 cardiomyocytes. We demonstrated that TRPV1 was indeed expressed in H9C2 cells, and activated by H/R injury. Although neuropeptide release caused by TRPV1 activation on sensory neurons elicits a cardioprotective effect, we found that capsaicin (CAP; a TRPV1 agonist) treatment of H9C2 cells paradoxically enhanced the level of apoptosis by increasing intracellular calcium and mitochondrial superoxide levels, attenuating mitochondrial membrane potential, and inhibiting mitochondrial biogenesis (measured by the expression of ATP synthase ß). In contrast, treatment of cells with capsazepine (CPZ; a TRPV1 antagonist) or TRPV1 siRNA attenuated H/R induced-apoptosis. Furthermore, CAP and CPZ treatment revealed a similar effect on cell viability and mitochondrial superoxide production in primary cardiomyocytes. Finally, using both CGRP(8-37) (a CGRP receptor antagonist) and RP67580 (a SP receptor antagonist) to exclude the confounding effects of neuropeptides, we confirmed aforementioned detrimental effects as TRPV1(-/-) mouse hearts exhibited improved cardiac function during ischemia/reperfusion. In summary, direct activation of TRPV1 in myocytes exacerbates H/R-induced apoptosis, likely through calcium overload and associated mitochondrial dysfunction. Our study provides a novel understanding of the role of myocyte TRPV1 channels in ischemia/reperfusion injury that sharply contrasts with its known extracardiac neuronal effects.

Seasonal Variations in Voluntary Intake and Apparent Digestibility of Forages in Goats Grazing on Introduced Leymus chinensis Pasture.

The nutrient composition of pasture, voluntary intake and digestibility of diet ingested by goats grazing on an introduced Leymus chinensis pasture were measured across spring (May), summer (July), autumn (October) and winter (March). In each season, 12 Inner Mongolian Cashmere goats (6 wethers and 6 does with an average live weight of 22.2±1.3 kg and 19.5±0.8 kg, respectively) were used to graze on a 2 hectares size paddock. Diet selection was observed and the plant parts selected by grazing goats and whole plant L. chinensis were sampled simultaneously. The alkane pair C32:C33 and C36 were used to estimate intake and digestibility, respectively. The results showed that the plant parts selected by goats had higher crude protein (CP) and lower acid detergent fiber (ADF) and neutral detergent fiber (NDF) than the whole plant, especially in the autumn and winter. The voluntary intake of dry matter (DM), CP, ADF, NDF, and metabolizable energy (ME) by goats was highest in summer (p<0.05). The goats ingested more CP, ME, and less ADF in spring than in autumn (p<0.05). The intakes of DM, CP, and ME were lowest in winter (p<0.05). There were significant differences in nutrient intake between wethers and does in each season, except for the ADF and ME intake per metabolic weight (LW(0.75)). The nutrient digestibilities were higher in spring and summer, and decreased significantly during the autumn and winter (p<0.05). Goats, especially wethers, had a relative constant NDF digestibility across seasons, however, the apparent digestibility of CP in both wethers and does, decreased to negative values in winter. The grazing goats experienced relatively sufficient nutrients supply in spring and summer, and a severe deficiency of CP and ME in winter.

Guanidinoacetic acid regulated postmortem muscle glycolysis associated with AMPK signaling and protein acetylation.

Objective: Antemortem stress accelerated muscle energy consumption in postmortem muscle. The objective of our study was to investigate the regulation of guanidinoacetic acid (GAA) administration on the postmortem glycolysis and protein acetylation in postmortem muscle of antemortem stress. Methods: Forty C57BL/6 male mice were chosen and randomly assigned to four treatment groups (A, B, C and D), each treatment consisted of 10 replicates. Mice in group B, C and D were treated with 0.05% GAA oral administration for 6 days. On the 7th day of the experiment, the mice in group A and B were injected with saline, and mice in group C and D were injected with 5-aminoimidazole-4-carboxamide1-ß-D-ribofuranoside (AICAR,50 µg/g body weight) and a combined injection with AICAR (50 µg/g body weight) and histone acetylase inhibitor Ⅱ (HAT Ⅱ,185 µg/g body weight), respectively. Results: The results showed that the values of pH45min and pH24h of postmortem muscle in GAA administration were higher than those in the control group. However, the opposite result was observed in AICAR group. Moreover, the activities of acetone kinase, hexokinase and fruc-tose-2,6-diphosphatase, combined with the protein abundance of phosphorylated liver kinase, phosphorylated AMPKα2 and total acetylated protein were all decreased by GAA administration and HAT Ⅱ treatment. Conclusion: Taken together, AMPK signaling and protein acetylation could mediate the regulation of GAA administration on postmortem glycolysis of antemortem stress-muscle.