β₁-adrenergic receptor autoantibodies (β₁-AAs) and β₂-adrenergic receptor autoantibodies (β₂-AAs) are present in patients with heart failure (HF); however, their interrelationship with cardiac structure and function remains unknown. This study explored the effects of the imbalance between β₁-AAs and β₂-AAs on cardiac structure and its underlying mechanisms in HF. Patients with left systolic HF who suffered from coronary heart disease (65.9%) or dilated cardiomyopathy (34.1%) were divided into New York Heart Association Classes I–II (n = 51) and Classes III–IV (n = 37) and compared with healthy volunteers as controls (n = 41). Total immunoglobulin G from HF patient serum comprising β₁-AAs and/or β₂-AAs were determined and purified for in vitro studies from neonatal rat cardiomyocytes (NRCMs). In addition, HF was induced by doxorubicin in mice. We observed that the increased ratio of β₁-AAs/β₂-AAs was associated with worsening HF in patients. Moreover, β₂-AAs from patients with HF suppressed the hyper-shrinking and apoptosis of NRCMS induced by β₁-AAs from some patients. Finally, β₂-AAs alleviated both myocardial damage and β₁-AAs production induced by doxorubicin in mice. β₂-AAs were capable of antagonizing the effects imposed by β₁-AAs both in vitro and in vivo. The imbalance of β₁-AAs and β₂-AAs in patients with HF is a mechanism underlying HF progression, and the increasing ratio of β₁-AAs/β₂-AAs should be considered a clinical assessment factor for the deterioration of cardiac function in patients with HF.

Upcycling of nutrients from residual resources for producing microbial protein (MP) is an attractive method to valorize residues. In this study, we investigated bio-electrochemical methods to recover ammonia-N, for further production of MP. Reject water and digestate were used for ammonia-N recovery in microbial fuel cell (MFC) system. In one-stage process, ammonia-N recovery was 32 - 42% with 57 - 154 kJ/m³ waste stream of electricity generation. For further enhancing recovery efficiency, a two-stage process was developed, achieving efficiency of 53 - 61%. Subsequently, MP was grown with the extracted ammonia-N, and amino acid concentration was 421 and 272 mg/L under 25 °C and 35 °C, respectively. Similar essential amino acid content of MP (especially under 25 °C) with the one from fish demonstrated the attractiveness of upcycling residues to proteins. Based on simplified economic evaluation, the produced energy performed the potential to catch 1.63 - 6.54 €/m³ waste stream.

Moyamoya disease (MMD) is an idiopathic disease associated with recurrent stroke. However, the pathogenesis of MMD remains unknown. Therefore, we performed long noncoding RNA (lncRNA) and messenger RNA (mRNA) expression profiles in blood samples from MMD patients (N = 15) and healthy controls (N = 10). A total of 880 differentially expressed lncRNAs (3649 probes) and 2624 differentially expressed mRNAs (2880 probes) were obtained from the microarrays of MMD patients and healthy controls (P < 0.05; Fold Change >2.0). Gene ontology (GO) and pathway analyses showed that upregulated mRNAs were enriched for inflammatory response, Toll-like receptor signaling pathway, chemokine signaling pathway and mitogen-activated protein kinase (MAPK) signaling pathway among others, while the downregulated mRNAs were enriched for neurological system process, digestion, drug metabolism, retinol metabolism and others. Our results showed that the integrated analysis of lncRNA-mRNA co-expression networks were linked to inflammatory response, Toll-like signaling pathway, cytokine-cytokine receptor interaction and MAPK signaling pathway. These findings may elucidate the pathogenesis of MMD, and the differentially expressed genes could provide clues to find key components in the MMD pathway.

In order to investigate the role of nitrative stress in vascular endothelial injury in hyperhomocysteinemia (HHcy), thirty healthy adult female Wistar rats were randomly divided into three groups: control, hyperhomocysteinemia model, and hyperhomocysteinemia with FeTMPyP (peroxynitrite scavenger) treatment. The endothelium-dependent dilatation of thoracic aorta in vitro was determined by response to acetylcholine (ACh). The histological changes in endothelium were assessed by HE staining and scanning electron microscopy (SEM). The expression of 3-nitrotyrosine (NT) in thoracic aorta was demonstrated by immunohistochemistry and immunofluorescence, and the number of circulating endothelial progenitor cells (EPCs) was quantified by flow cytometry. Hyperhomocysteinemia caused significant endothelial injury and dysfunction including vasodilative and histologic changes, associated with higher expression of NT in thoracic aorta. FeTMPyP treatment reversed these injuries significantly. Further, the effect of nitrative stress on cultured EPCs in vitro was investigated by administering peroxynitrite donor (3-morpholino-sydnonimine, SIN-1) and peroxynitrite scavenger (FeTMPyP). The roles of nitrative stress on cell viability, necrosis and apoptosis were evaluated with 3-(4,5-dimethylthiazol)-2,5-diphenyl tetrazolium (MTT) assay, lactate dehydrogenase (LDH) release assay and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay, respectively. Also, the phospho-eNOS expression and tube formation in Matrigel of cultured EPCs was detected. Our data showed that the survival of EPCs was much lower in SIN-1 group than in vehicle group, both the apoptosis and necrosis of EPCs were much more severe, and the p-eNOS expression and tube formation in Matrigel were obviously declined. Subsequent pretreatment with FeTMPyP reversed these changes. Further, pretreatment with FeTMPyP reversed homocysteine-induced EPC injury. In conclusion, this study indicates that nitrative stress plays a role in vascular endothelial injury in hyperhomocysteinemia, as well as induces endothelial progenitor cell injury directly.

Aims: Hyperhomocysteinemia (HHcy) has been considered as a risk factor for cardiovascular disease, Alzheimer's disease, nonalcoholic fatty liver, and many other pathological conditions. Vitamin B6, Vitamin B12, and folate have been used to treat HHcy in clinics. However, at present, clinical therapies of HHcy display unsatisfactory effects. Here, we would like to explore a new mechanism involved in homocysteine (Hcy) metabolic disorders and a novel target for HHcy treatment. The key enzymes involved in Hcy metabolism deserve more insightful investigation. Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme regulating the intracellular Hcy metabolism. Until now, the effect of post-translational modification on the bioactivity of MTHFR still remains unclear. This study aimed at exploring the relationship between MTHFR S-sulfhydration and its bioactivity, and at identifying the contribution of an elevated Hcy level on MTHFR bioactivity. Results: By both in vivo and in vitro studies, we observed the following results: (i) The bioactivity of MTHFR was positively associated with its S-sulfhydration level; (ii) MTHFR was modified at Cys32, Cys130, Cys131, Cys193, and Cys306 by S-sulfhydration under physiological conditions; (iii) Hydrogen sulfide (H ₂ S) deficiency caused the decrease of MTHFR S-sulfhydration level and bioactivity in HHcy, which resulted in further aggravation of HHcy; and (iv) H ₂ S donors reversed the decreased bioactivity of MTHFR in HHcy, thus reducing the excessive Hcy level. Innovation and Conclusion: Our study suggested that H ₂ S could improve MTHFR bioactivity by S-sulfhydration, which might provide a candidate therapeutic strategy for HHcy. Antioxid. Redox Signal . 36, 1–14.