Regulation Of Reactive Oxygen Species Research Articles

ROS scavenging carbon dots chelated hydroxyapatite filler: Target synthesis and enhancing adhesion of hydrogel

Carbon dots/hydroxyapatite filler could have the reactive oxygen species (ROS) scavenging ability of CDs and the mechanical property improvement ability of hydroxyapatite. Carbon dots (CDs) not only have optical fluorescence by its physical property, but also regulates ROS by its biological property and had the binding ability of calcium ions by its chemical property. Based on the chelation ability and ROS regulation ability of CDs, ROS scavenging carbon dots chelated hydroxyapatite filler (ROS-HA) was target synthesized via chelating ability and the synthetic yield was 70.9%. The chelation sites of CDs were 2.89 ± 0.02 and after chelated hydroxyapatite, the chelation sites of ROS-HA were 0.69 ± 0.02. The maximum hydroxyl radical scavenging rate and superoxide radical scavenging rate of ROS-HA were 72% and 60%, respectively. ROS-HA improved 86% the adhesion performance of hydrogel-based composites compared to the hydrogel. ROS-HA provided new filler for construction the ROS regulation, tissue adhesive and fluorescent hydrogel application in wound dressing.

Redox Regulation of Autophagy in Cancer: Mechanism, Prevention and Therapy.

Reactive oxygen species (ROS), products of normal cellular metabolism, play an important role in signal transduction. Autophagy is an intracellular degradation process in response to various stress conditions, such as nutritional deprivation, organelle damage and accumulation of abnormal proteins. ROS and autophagy both exhibit double-edged sword roles in the occurrence and development of cancer. Studies have shown that oxidative stress, as the converging point of these stimuli, is involved in the mechanical regulation of autophagy process. The regulation of ROS on autophagy can be roughly divided into indirect and direct methods. The indirect regulation of autophagy by ROS includes post-transcriptional and transcriptional modulation. ROS-mediated post-transcriptional regulation of autophagy includes the post-translational modifications and protein interactions of AMPK, Beclin 1, PI3K and other molecules, while transcriptional regulation mainly focuses on p62/Keap1/Nrf2 pathway. Notably, ROS can directly oxidize key autophagy proteins, such as ATG4 and p62, leading to the inhibition of autophagy pathway. In this review, we will elaborate the molecular mechanisms of redox regulation of autophagy in cancer, and discuss ROS- and autophagy-based therapeutic strategies for cancer treatment.

Role of Phosphoinositide 3-Kinase in Regulation of NOX-Derived Reactive Oxygen Species in Cancer.

Activation of NADPH oxidases (NOX) and the ensuing formation of reactive oxygen species (ROS) is a vital aspect of antimicrobial defense but may also promote tumorigenesis. Enhanced NOX activity has been associated with aberrant activation of oncogenic cascades such as the phosphoinositide 3-kinase (PI3K) signaling pathway, which is upregulated in several malignancies. In this review, we examine the role of PI3K on the regulation of NOX-induced ROS formation in cancer.

A Chloroplast-Localized Glucose-6-Phosphate Dehydrogenase Positively Regulates Stripe Rust Resistance in Wheat.

Glucose-6-phosphate dehydrogenase (G6PDH), the rate-limiting enzyme of the pentose phosphate pathway (PPP), plays a pivotal role in plant stress responses. However, the function and mechanism of G6PDHs in crop plants challenged by fungal pathogens remain poorly understood. In this study, a wheat G6DPH gene responding to infection by Puccinia striiformis f. sp. tritici (Pst), designated TaG6PDH2, was cloned and functionally identified. TaG6PDH2 expression was significantly upregulated in wheat leaves inoculated with Pst or treated with abiotic stress factors. Heterologous mutant complementation and enzymatic properties indicate that TaG6PDH2 encodes a G6PDH protein. The transient expression of TaG6PDH2 in Nicotiana benthamiana leaves and wheat protoplasts revealed that TaG6PDH2 is a chloroplast-targeting protein. Silencing TaG6PDH2 via the barley stripe mosaic virus (BSMV)-induced gene silencing (VIGS) system led to compromised wheat resistance to the Pst avirulent pathotype CYR23, which is implicated in weakened H2O2 accumulation and cell death. In addition, TaG6PDH2 was confirmed to interact with the wheat glutaredoxin TaGrxS4. These results demonstrate that TaG6PDH2 endows wheat with increased resistance to stripe rust by regulating reactive oxygen species (ROS) production.

Nanomaterials-Functionalized Hydrogels for the Treatment of Cutaneous Wounds.

Hydrogels have been utilized extensively in the field of cutaneous wound treatment. The introduction of nanomaterials (NMs), which are a big category of materials with diverse functionalities, can endow the hydrogels with additional and multiple functions to meet the demand for a comprehensive performance in wound dressings. Therefore, NMs-functionalized hydrogels (NMFHs) as wound dressings have drawn intensive attention recently. Herein, an overview of reports about NMFHs for the treatment of cutaneous wounds in the past five years is provided. Firstly, fabrication strategies, which are mainly divided into physical embedding and chemical synthesis of the NMFHs, are summarized and illustrated. Then, functions of the NMFHs brought by the NMs are reviewed, including hemostasis, antimicrobial activity, conductivity, regulation of reactive oxygen species (ROS) level, and stimulus responsiveness (pH responsiveness, photo-responsiveness, and magnetic responsiveness). Finally, current challenges and future perspectives in this field are discussed with the hope of inspiring additional ideas.

Neuroprotective Effect of the Mixture of Gastrodiae elata and Glycyrrhizae uralensis In Vitro

Background: This study investigated the effect of a mixture of Gastrodiae elata and Glycyrrhizae uralensis (GGW) on β-amyloid-induced neuronal damage in vitro. Methods: For finding the appropriate GGW ratio, we performed MTT assays using the ratios of 5:5, 6:4, 7:3, 8:2 and 9:1 in SK-N-SH cell and SH-SY-5Y cell. Treatment with β-amyloid (10 μM) caused cell death and overexpression of acetylcholinesterase (ACHE) in SH-SY-5Y cells. β-amyloid treatment increased the expression of mitogen-activated protein kinases (MAPKs). In addition, we detected the antioxidant activity of GGW using DCF-DA staining of SK-N-SH cells. To determine the effect of GGW on oxidative stress, we used a hydrogen peroxidase-induced in vitro model. Results: We selected the ratios of 5:5 and 7:3 mixtures with the least cytotoxicity. The 7:3 ratio of GGW (GGW73) decreased the mRNA expression of ACHE in SH-SY-5Y cell more than the 5:5 ratio of GGW (GGW55). GGW73 suppressed p-ERK protein expression in β-amyloid-treated SH-SY-5Y cells. Additionally, GGW73 regulated reactive oxygen species (ROS) in vitro. GGW73 treatment regulated apoptotic factors in β-amyloid-stimulated neuronal cells. Conclusions: These results suggest that GGW73 exerts neuroprotective and anti-inflammatory effects in vitro. These results also showed that GGW73 had a protective effect against H2O2 induced cell damage in an in vitro model. These results indicate the potential of GGW as a therapeutic agent for cognitive disorders.

Molecular interactions of adaptor protein PSTPIP2 control neutrophil-mediated responses leading to autoinflammation.

Autoinflammatory diseases are characterized by dysregulation of innate immune system leading to spontaneous sterile inflammation. One of the well-established animal models of this group of disorders is the mouse strain Pstpip2cmo . In this strain, the loss of adaptor protein PSTPIP2 leads to the autoinflammatory disease chronic multifocal osteomyelitis. It is manifested by sterile inflammation of the bones and surrounding soft tissues of the hind limbs and tail. The disease development is propelled by elevated production of IL-1β and reactive oxygen species by neutrophil granulocytes. However, the molecular mechanisms linking PSTPIP2 and these pathways have not been established. Candidate proteins potentially involved in these mechanisms include PSTPIP2 binding partners, PEST family phosphatases (PEST-PTPs) and phosphoinositide phosphatase SHIP1. To address the role of these proteins in PSTPIP2-mediated control of inflammation, we have generated mouse strains in which PEST-PTP or SHIP1 binding sites in PSTPIP2 have been disrupted. In these mouse strains, we followed disease symptoms and various inflammation markers. Our data show that mutation of the PEST-PTP binding site causes symptomatic disease, whereas mice lacking the SHIP1 interaction site remain asymptomatic. Importantly, both binding partners of PSTPIP2 contribute equally to the control of IL-1β production, while PEST-PTPs have a dominant role in the regulation of reactive oxygen species. In addition, the interaction of PEST-PTPs with PSTPIP2 regulates the production of the chemokine CXCL2 by neutrophils. Its secretion likely creates a positive feedback loop that drives neutrophil recruitment to the affected tissues. We demonstrate that PSTPIP2-bound PEST-PTPs and SHIP1 together control the IL-1β pathway. In addition, PEST-PTPs have unique roles in the control of reactive oxygen species and chemokine production, which in the absence of PEST-PTP binding to PSTPIP2 shift the balance towards symptomatic disease.

Comparative Analysis of Physiological, Hormonal and Transcriptomic Responses Reveal Mechanisms of Saline-Alkali Tolerance in Autotetraploid Rice (Oryza sativa L.).

Saline-alkali soil has posed challenges to the growth of agricultural crops, while polyploidy often show greater adaptability in diverse and extreme environments including saline-alkali stress, but its defense mechanisms in rice remain elusive. Herein, we explored the mechanisms of enhanced saline-alkali tolerance of autotetraploid rice 93-11T relative to diploid rice 93-11D, based on physiological, hormonal and transcriptomic profilings. Physiologically, the enhanced saline-alkali tolerance in 93-11T was manifested in higher soluble sugar accumulation and stronger superoxide dismutase (SOD) and peroxidase (POD) activities in leaves during 24 h after saline-alkali shock. Furthermore, various hormone levels in leaves of 93-11T altered greatly, such as the negative correlation between salicylic acid (SA) and the other four hormones changed to positive correlation due to polyploidy. Global transcriptome profiling revealed that the upregulated differentially expressed genes (DEGs) in leaves and roots of 93-11T were more abundant than that in 93-11D, and there were more DEGs in roots than in leaves under saline-alkali stress. Genes related to phytohormone signal transduction of auxin (AUX) and SA in roots, lignin biosynthesis in leaves or roots, and wax biosynthesis in leaves were obviously upregulated in 93-11T compared with 93-11D under saline-alkali condition. Collectively, 93-11T subjected to saline-alkali stress possibly possesses higher osmotic regulation ability due to cuticular wax synthesis, stronger negative regulation of reactive oxygen species (ROS) production by increasing the SA levels and maintaining relative lower levels of IAA, and higher antioxidant capacity by increasing activities of SOD and POD, as well as lignin biosynthesis. Our research provides new insights for exploring the mechanisms of saline-alkali tolerance in polyploid rice and discovering new gene targets for rice genetic improvement.

Protein-protein interactions in plant antioxidant defense.

The regulation of reactive oxygen species (ROS) levels in plants is ensured by mechanisms preventing their over accumulation, and by diverse antioxidants, including enzymes and nonenzymatic compounds. These are affected by redox conditions, posttranslational modifications, transcriptional and posttranscriptional modifications, Ca2+, nitric oxide (NO) and mitogen-activated protein kinase signaling pathways. Recent knowledge about protein-protein interactions (PPIs) of antioxidant enzymes advanced during last decade. The best-known examples are interactions mediated by redox buffering proteins such as thioredoxins and glutaredoxins. This review summarizes interactions of major antioxidant enzymes with regulatory and signaling proteins and their diverse functions. Such interactions are important for stability, degradation and activation of interacting partners. Moreover, PPIs of antioxidant enzymes may connect diverse metabolic processes with ROS scavenging. Proteins like receptor for activated C kinase 1 may ensure coordination of antioxidant enzymes to ensure efficient ROS regulation. Nevertheless, PPIs in antioxidant defense are understudied, and intensive research is required to define their role in complex regulation of ROS scavenging.

L-carnosine Attenuates Bleomycin-Induced Oxidative Stress via NFκB Pathway in the Pathogenesis of Pulmonary Fibrosis.

Idiopathic Pulmonary fibrosis (IPF), a chronic interstitial lung disease, has pulmonary manifestations clinically characterized by collagen deposition, epithelial cell injury, and a decline in lung function. L-carnosine, a dipeptide consisting of β-alanine and L-histidine, has demonstrated a therapeutic effect on various diseases because of its pivotal function. Despite the effect of L-carnosine in experimental IPF mice, its anti-oxidative effect and associated intercellular pathway, particularly alveolar epithelial cells, remain unknown. Therefore, we demonstrated the anti-fibrotic and anti-inflammatory effects of L-carnosine via Reactive oxygen species (ROS) regulation in bleomycin (BLM)-induced IPF mice. The mice were intratracheally injected with BLM (3 mg/kg) and L-carnosine (150 mg/kg) was orally administrated for 2 weeks. BLM exposure increased the protein level of Nox2, Nox4, p53, and Caspase-3, whereas L-carnosine treatment suppressed the protein level of Nox2, Nox4, p53, and Caspase-3 cleavage in mice. In addition, the total SOD activity and mRNA level of Sod2, catalase, and Nqo1 increased in mice treated with L-carnosine. At the cellular level, a human fibroblast (MRC-5) and mouse alveolar epithelial cell (MLE-12) were exposed to TGFβ1 following L-carnosine treatment to induce fibrogenesis. Moreover, MLE-12 cells were exposed to cigarette smoke extract (CSE). Consequently, L-carnosine treatment ameliorated fibrogenesis in fibroblasts and alveolar epithelial cells, and inflammation induced by ROS and CSE exposure was ameliorated. These results were associated with the inhibition of the NFκB pathway. Collectively, our data indicate that L-carnosine induces anti-inflammatory and anti-fibrotic effects on alveolar epithelial cells against the pathogenesis of IPF.

Leaves of Cedrela sinensis Attenuate Chronic Unpredictable Mild Stress-Induced Depression-like Behavior via Regulation of Hormonal and Inflammatory Imbalance.

This study aimed to evaluate the protective effects of ethyl acetate fraction from Cedrela sinensis (EFCS) against chronic unpredictable mild stress (CUMS)-induced behavioral dysfunction and stress response in C57BL/6 mice. The physiological compounds of EFCS were identified as rutin, isoquercitrin, ethyl gallate, quercitrin, kaempferol-3-O-rhamnoside, and ethyl digallate, using UPLC-Q-TOF/MSE. To evaluate the neuroprotective effect of EFCS, H2O2- and corticosterone-induced neuronal cell viability was conducted in human neuroblastoma MC-IXC cells. It was found that EFCS alleviated depression-like behavior by conducting the sucrose preference test (SPT), forced swimming test (FST), open field test (OFT), and tail suspension test (TST). EFCS inhibited mitochondrial dysfunction related to neuronal energy metabolism by regulating reactive oxygen species (ROS) levels, mitochondrial membrane potential (MMP), and ATP contents in brain tissue. In addition, the administration of EFCS regulated the stress hormones in serum. EFCS regulated stress-related indicators such as CRF, ACTH, CYP11B1, and BDNF. Moreover, EFCS downregulated the inflammatory responses and apoptosis proteins such as caspase-1, TNF-α, IL-1β, p-JNK, BAX, and p-tau in brain tissues. These results suggest that EFCS might be a potential natural plant material that alleviates CUMS-induced behavior disorder by regulating inflammation in brain tissue against CUMS-induced depression.

Molecular cloning and characterization of a thioredoxin-like protein gene in rotifer Brachionus plicatilis

The thioredoxin-like protein exists widely, in various organisms, as a regulator of redox homeostasis. In this study, the full-length cDNA of a thioredoxin-like protein gene from rotifer Brachionus plicatilis (designated as BpTXNL) was obtained by 5′ rapid amplification of cDNA end (RACE) technology. The complete cDNA of BpTXNL was 1111 bp, and contained a 5′ untranslated region (UTR) of 69 bp, a 3’ UTR of 163 bp with a polyadenylate additional signal and a polyadenylation site (PAS), and an open reading frame (ORF) of 878 bp, encoding 292 amino acids. The calculated molecular weight and the theoretical isoelectric point (pI) of the deduced BpTXNL peptide were 32.7 kDa and 4.97, respectively. The deduced protein sequence of BpTXNL contained a thioredoxin domain with the conserved redox-active site at 33CGPC36 and a proteasome-interacting thioredoxin (PITH) domain. Phylogenetic analysis demonstrated that BpTXNL was clustered with TXNLs of Strongyloides ratti and Caenorhabditis elegans. The temporal mRNA expression level of BpTXNL significantly decreased at 6 h, then increased to the peak 24h after the 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47) challenge, while the mRNA transcripts of BpTXNL significantly increased and reached the peaks twice, at 6 h and 24 h after the lipopolysaccharide (LPS) challenge. The recombinant BpTXNL protein quickly exhibited a concentration-dependent antioxidant capacity and the peak occurred at 55 min in the 20 μM group. All these results showed that BpTXNL possesses an antioxidant capacity, and that it may be involved in the regulation of excessive reactive oxygen species (ROS) during environmental stress or pathogen invading.

A novel derivative of Genistein inhibits proliferation of ovarian cancer HO-8910 cells by regulating reactive oxygen species*

Abstract Objective To investigate the anticancer effect of a novel derivative of genistein (5-hydroxy-4′-nitro-7-propionyloxy-genistein, HNPG) on human ovarian cancer HO-8910 cells and its possible molecular mechanism. Methods HO-8910 cells were cultured in vitro, and the inhibitory effect of HNPG on proliferation was determined using MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. The effect of HNPG on inducing apoptosis was examined using FCM with Annexin V-FITC and propidium iodide staining. The effect of HNPG on regulating reactive oxygen species (ROS) was measured using FCM with 2′,7′-di chlorodihydro-fluorescein diacetate staining. The effect of HNPG on modulating mitochondrial membrane potential (MMP) was determined using FCM with lipophilic cationic dye 2 (6 Amino 3 imino 3H xanthen 9 yl) benzoic acid methyl ester (Rh123) staining. The bioactivity of superoxide dismutase (SOD) and catalase (CAT) and the content of glutathione (GSH) and malondialdehyde (MDA) were detected using enzyme-linked immunosorbent assay. The related apoptotic proteins, including bcl-2, bax, cyt-c, and cleaved-caspase-3, were assessed using western blotting. Results HNPG exhibited dramatic antitumor activity against HO-8910 cells in vitro, inhibited proliferation, and induced apoptosis in a time- and dose-dependent manner. These effects were accompanied by reduced bioactivity of SOD and CAT, reduced GSH content, and enhanced MDA content. Simultaneously, the amount of ROS was increased and the level of MMP was reduced, along with upregulation of mitochondrial apoptosis pathway-related proteins, bax, cyt-c, and cleaved-caspase-3; bcl-2 protein was downregulated. Conclusion HNPG inhibited proliferation of human ovarian cancer HO-8910 cells in vitro, which might be related to decreased bioactivity of SOD and CAT. HNPG also reduced GSH content, which resulted in ROS accumulation in cells, damaged the integrity of mitochondrial membrane, and induced cell apoptosis.

Regulation of reactive oxygen species on the mitophagy of human periodontal ligament cells through the PINK1/Parkin pathway under starvation.

This study aimed to explore the specific mechanism, mediated by the reactive oxygen species (ROS) and PINK1/Parkin pathway, of the mitochondrial autophagy of human periodontal ligament cells (hPDLCs) under starvation conditions. hPDLCs were isolated and cultured from normal periodontal tissues. Earle's balanced salt solution (EBSS) was used to simulated a starvation environment and thus stimulate hPDLCs mitochondrial autophagy. N-Acetyl-L-cysteine (NAC) was used to inhibit ROS production to explore the role of ROS in hPDLC mitochondrial autophagy. Cyclosporin A was used to inhibit the PINK1/Parkin pathway to study the role of ROS and the PINK1/Parkin pathway in hPDLCs activation under starvation. The mitochondrial membrane potential was detected by flow cytometry with a JC-1 mitochondrial membrane potential detection kit. The morphological structure of mitochondria and the formation of mitochondrial autophagosome were observed by transmission electron microscopy. Mito tracker red cmxros and lyso tracker green staining were used to observe the localization of mitochondria and lysosomes. The formation intensity of ROS was detected with a DCFH-DA ROS fluorescent probe. The expression levels of mitochondrial autophagy genes (Tomm20 and Timm23) and the PINK1/Parkin pathway were detected by real-time quantitative polymerase chain reaction (RT-qPCR). The expression levels of mitochondrial autophagy proteins (Tomm20 and Timm23) and PINK1/Parkin protein were detected by Western blot. EBSS starvation for 30 min induced the strongest activation of hPDLCs mitochondrial autophagy, increased the expression of ROS, downregulated the expression of mitochondrial autophagy-related genes (Tomm20 and Timm23) (P<0.001), and upregulated the PINK1/Parkin pathway (P<0.001). After NACinhibited ROS production, mitochondrial autophagy was also inhibited. Meanwhile, the expression of Tomm20 and Timm23 was upregulated (P<0.001 and P<0.05), and the expression of the PINK1/parkin pathway (P<0.001 and P<0.05) was down regulated. When cyclosporin A inhibited the expression of the PINK1/Parkin pathway (P<0.05 and P<0.05), it reversed the mitochondrial autophagy of hPDLCs (P<0.001 and P<0.01) and also upregulated the expression of Tomm20 and Timm23 (P<0.001 and P<0.01). ROS enhanced the mitochondrial autophagy of hPDLCs primarily through the PINK1/Parkin pathway under starvation conditions.

Integration of Transcriptome and Metabolome Analyses Reveals the Mechanistic Basis for Cadmium Accumulation in Maize.

Cadmium (Cd) pollution in soil has become a major environmental issue worldwide. However, the underlying molecular mechanism of low grain-Cd accumulation (GCA) in maize is still largely unknown. Herein, we report the mechanistic basis for low GCA in maize by a multiomics approach. The low GCA genotype L63 showed normal vacuolar formation and a lower capacity of xylem loading of Cd than the high-accumulator L42 under Cd stress. Transcriptomic sequencing identified 84 low-GCA-associated genes which are mainly involved in the S-adenosylmethionine (SAM) cycle, metal transport, and vacuolar sequestration. A metabolome analysis revealed that L63 plants had a more active SAM cycle and a greater capacity for terpenoid synthesis and phenylalanine metabolism than L42. Combining the analysis of transcriptome and metabolome characterized several genes as key genes involved in the determination of Cd accumulation. Our study identifies a mechanistic basis for low Cd accumulation in maize grains and provides candidate genes for genetic improvement of crops.

Regulation of reactive oxygen species on production, release, and early germination of archeospores in Pyropia yezoensis

In plant, reactive oxygen species (ROS) play important regulatory roles in cell differentiation and development. The archeospores released from the blades of Pyropia yezoensis have important application value as secondary seedling sources in cultivation. However, whether ROS are involved in the production and early germination of archeospores of P. yezoensis is unclear. In this study, in situ ROS fluorescence detection was developed to observe the regulation of ROS on the processes of formation, release and germination of archeospores of P. yezoensis. The results are as follows, there was no ROS fluorescence in the marginal bladed cells of P. yezoensis with no formed archeospores, but strong ROS fluorescence in the marginal cells while releasing archeospores. Next, intensive ROS fluorescence was emerged in released archeospores which carried on amoeboid movement with irregular cell shape. Then, after the archeospores adhered to the glass substrate, the ROS fluorescence faded rapidly, accompanied with round cell shape, and formed cell wall. When the cells elongated for the first germination and division, ROS fluorescence disappeared eventually, and there was no ROS fluorescence in the germlings with two and more cells. On the other hand, by culturing the somatic cells isolated from the blades, ROS fluorescence could be continuously detected from stage of single cells to cell-masses composed of multiple cells, the intensity of which was raised with the increasing numbers of cells in the cell-mass. When the cells in cell-masses differentiated into archeospores, the ROS fluorescent intensity reached the peak. As the addition of diphenyleneiodonium (DPI) could inhibit the production of ROS, the speed of cell division was significantly affected and the ROS fluorescent intensity was decreased during treatment. The above results confirmed that ROS play roles in the regulation on the formation, release and early germination of archeospores of P. yezoensis.

Effect of BIO-PLYTM, a Platelet-Rich Plasma Derived Biologic on PRRSV-2-Infected Macrophages.

Porcine Reproductive and Respiratory Syndrome (PRRS) is the one of the most devastating diseases impacting the swine industry worldwide. Control and prevention methods rely on biosafety measures and vaccination. As an RNA virus with a high rate of mutation, vaccines are only partially effective against circulating and newly emerging strains. To reduce the burden of this disease, research on alternative control methods is needed. Here, we assess the in vitro antiviral effect of a novel platelet-rich plasma-derived biologic termed BIO-PLYTM (for the BIOactive fraction of Platelet-rich plasma LYsate) from both swine and equine origin. Our results show that BIO-PLYTM significantly reduces the amount of PRRSV viral load determined by RT-qPCR and the number of infectious viral particles measured by TCID50 in infected porcine alveolar and parenchymal macrophages. This study also showed limited toxicity of BIO-PLYTM in vitro and aspects of its immunomodulatory capacity evaluating the regulation of reactive oxygen species and cytokines production in infected cells. Finally, this study presents promising data on the effect of BIO-PLYTM on other RNA viruses such as human A influenza viruses and coronavirus.

α-Synuclein aggregation causes muscle atrophy through neuromuscular junction degeneration.

Sarcopenia is common in patients with Parkinson's disease (PD), showing mitochondrial oxidative stress in skeletal muscle. The aggregation of α-synuclein (α-Syn) to induce oxidative stress is a key pathogenic process of PD; nevertheless, we know little about its potential role in regulating peripheral nerves and the function of the muscles they innervate. To investigate the role of α-Syn aggregation on neuromuscular system, we used the Thy1 promoter to overexpress human α-Syn transgenic mice (mThy1-hSNCA). hα-Syn expression was evaluated by western blot, and its localization was determined by confocal microscopy. The impact of α-Syn aggregation on the structure and function of skeletal muscle mitochondria and neuromuscular junctions (NMJs), as well as muscle mass and function were characterized by flow cytometry, transmission electron microscopy, Seahorse XF24 metabolic assay, and AAV9 in vivo injection. We assessed the regenerative effect of mitochondrial-targeted superoxide dismutase (Mito-TEMPO) after skeletal muscle injury in mThy1-hSNCA mice. Overexpressed hα-Syn protein localized in motor neuron axons and NMJs in muscle and formed aggregates. α-Syn aggregation increased the number of abnormal mitochondrial in the intramuscular axons and NMJs by over 60% (P<0.01), which inhibited the release of acetylcholine (ACh) from presynaptic vesicles in NMJs (P<0.05). The expression of genes associated with NMJ activity, neurotransmission and regulation of reactive oxygen species (ROS) metabolic process were significantly decreased in mThy1-hSNCA mice, resulting in ROS production elevated by ~220% (P<0.05), thereby exacerbating oxidative stress. Such process altered mitochondrial spatial relationships to sarcomeric structures, decreased Z-line spacing by 36% (P<0.05) and increased myofibre apoptosis by ~10% (P<0.05). Overexpression of α-Syn altered the metabolic profile of muscle satellite cells (MuSCs), including basal respiratory capacity (~170% reduction) and glycolytic capacity (~150% reduction) (P<0.05) and decreased cell migration and fusion during muscle regeneration (~60% and ~40%, respectively) (P<0.05). We demonstrated that Mito-TEMPO treatment could restore the oxidative stress status (the complex I/V protein and enzyme activities increased ~200% and ~150%, respectively), which caused by α-Syn aggregation, and improve the ability of muscle regeneration after injury. In addition, the NMJ receptor fragmentation and ACh secretion were also improved. These results reveal that the α-synuclein aggregation plays an important role in regulating acetylcholine release from neuromuscular junctions and induces intramuscular mitochondrial oxidative stress, which can provide new insights into the aetiology of muscle atrophy in patients with Parkinson's disease.

Unraveling the epitranscriptome of small non-coding RNAs in vascular cells

Unraveling the epitranscriptome of small non-coding RNAs in vascular cells

ROS-reactive PMS/PC drug delivery system improves new bone formation under diabetic conditions by promoting angiogenesis-osteogenesis coupling via down-regulating NOX2-ROS signalling axis

Reactive oxygen species (ROS) overproduction and oxidative stress increases bone fragility and fracture risk in long-standing diabetes mellitus cases. In this study, a ROS-reactive drug delivery system was prepared to solve this issue by phenyl sulfide mesoporous silica nanoparticles (PMS) loaded with proanthocyanidin (PC). The effect of PMS/PC on new bone formation under diabetic conditions and the underlying mechanism was investigated in-vitro and in-vivo. The results illustrated that the PC was released from the ROS-reactive PMS/PC triggered by peripheral ROS and then eliminated excessive ROS, which achieved dynamic ROS regulation and reached ROS homeostasis finally. Furthermore, we found PMS/PC promoted osteoblastic differentiation in vitro and increased ossification in vivo by promoting the angiogenesis-osteogenesis coupling via down-regulating the expression of nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) to suppress ROS overproduction, preventing vascular oxidative stress. Therefore, our work has proved a therapeutic potential of ROS-reactive PMS/PC in the treatment of diabetic bone disease and indicates excellent prospects of PMS/PC to depress oxidative stress triggered by excessive ROS which is a key pathological factor in many systematic diseases.