ConsRM: collection and large-scale prediction of the evolutionarily conserved RNA methylation sites, with implications for the functional epitranscriptome.

Motivation N6-methyladenosine (m6A) is the most prevalent RNA modification on mRNAs and lncRNAs. Evidence increasingly demonstrates its crucial importance in essential molecular mechanisms and various diseases. With recent advances in sequencing techniques, tens of thousands of m6A sites are identified in a typical high-throughput experiment, posing a key challenge to distinguish the functional m6A sites from the remaining 'passenger' (or 'silent') sites. Results: We performed a comparative conservation analysis of the human and mouse m6A epitranscriptomes at single site resolution. A novel scoring framework, ConsRM, was devised to quantitatively measure the degree of conservation of individual m6A sites. ConsRM integrates multiple information sources and a positive-unlabeled learning framework, which integrated genomic and sequence features to trace subtle hints of epitranscriptome layer conservation. With a series validation experiments in mouse, fly and zebrafish, we showed that ConsRM outperformed well-adopted conservation scores (phastCons and phyloP) in distinguishing the conserved and unconserved m6A sites. Additionally, the m6A sites with a higher ConsRM score are more likely to be functionally important. An online database was developed containing the conservation metrics of 177 998 distinct human m6A sites to support conservation analysis and functional prioritization of individual m6A sites. And it is freely accessible at: https://www.xjtlu.edu.cn/biologicalsciences/con.

RMDisease: a database of genetic variants that affect RNA modifications, with implications for epitranscriptome pathogenesis.

Deciphering the biological impacts of millions of single nucleotide variants remains a major challenge. Recent studies suggest that RNA modifications play versatile roles in essential biological mechanisms, and are closely related to the progression of various diseases including multiple cancers. To comprehensively unveil the association between disease-associated variants and their epitranscriptome disturbance, we built RMDisease, a database of genetic variants that can affect RNA modifications. By integrating the prediction results of 18 different RNA modification prediction tools and also 303,426 experimentally-validated RNA modification sites, RMDisease identified a total of 202,307 human SNPs that may affect (add or remove) sites of eight types of RNA modifications (m6A, m5C, m1A, m5U, Ψ, m6Am, m7G and Nm). These include 4,289 disease-associated variants that may imply disease pathogenesis functioning at the epitranscriptome layer. These SNPs were further annotated with essential information such as post-transcriptional regulations (sites for miRNA binding, interaction with RNA-binding proteins and alternative splicing) revealing putative regulatory circuits. A convenient graphical user interface was constructed to support the query, exploration and download of the relevant information. RMDisease should make a useful resource for studying the epitranscriptome impact of genetic variants via multiple RNA modifications with emphasis on their potential disease relevance. RMDisease is freely accessible at: www.xjtlu.edu.cn/biologicalsciences/rmd.

m6A-Atlas: a comprehensive knowledgebase for unraveling the N6-methyladenosine (m6A) epitranscriptome.

N 6-Methyladenosine (m6A) is the most prevalent RNA modification on mRNAs and lncRNAs. It plays a pivotal role during various biological processes and disease pathogenesis. We present here a comprehensive knowledgebase, m6A-Atlas, for unraveling the m6A epitranscriptome. Compared to existing databases, m6A-Atlas features a high-confidence collection of 442 162 reliable m6A sites identified from seven base-resolution technologies and the quantitative (rather than binary) epitranscriptome profiles estimated from 1363 high-throughput sequencing samples. It also offers novel features, such as; the conservation of m6A sites among seven vertebrate species (including human, mouse and chimp), the m6A epitranscriptomes of 10 virus species (including HIV, KSHV and DENV), the putative biological functions of individual m6A sites predicted from epitranscriptome data, and the potential pathogenesis of m6A sites inferred from disease-associated genetic mutations that can directly destroy m6A directing sequence motifs. A user-friendly graphical user interface was constructed to support the query, visualization and sharing of the m6A epitranscriptomes annotated with sites specifying their interaction with post-transcriptional machinery (RBP-binding, microRNA interaction and splicing sites) and interactively display the landscape of multiple RNA modifications. These resources provide fresh opportunities for unraveling the m6A epitranscriptomes. m6A-Atlas is freely accessible at: www.xjtlu.edu.cn/biologicalsciences/atlas.

Anthocyanin oligomer (grape skin extract) administration improves dry eye disease: A randomised, double-blind, placebo-controlled study.

BACKGROUND: Dry eye disease is a chronic, progressive ocular disease characterised by ocular discomfort and is one of the most common ophthalmological disorders that affects people's lives. METHODS: This study investigated the clinical efficacy of anthocyanin oligomers (grape skin extract) for the treatment of dry eye. One hundred and eight patients with dry eye were randomly divided into placebo and treatment groups, each with 54 cases. The placebo group received maltodextrin (800 mg/day) and the treatment group received anthocyanin oligomers (800 mg/day). Clinical efficacy, clinical indices, and occurrence of adverse reactions were compared between the two groups. RESULTS: Anthocyanin oligomers were safe and effective in mild-to-moderate dry eye disease, improving the tear break-up time, intraocular pressure, ocular surface disease, and patient symptomatology. CONCLUSIONS: The use of oral anthocyanin oligomers in the treatment of dry eye patients can enhance the therapeutic effect and improve the quality of life of patients while ensuring the safety of treatment, making this therapeutic option suitable for wider application.

Funm6AViewer: a web server and R package for functional analysis of context-specific m6A RNA methylation.

MOTIVATION: N 6-methyladenosine (m6A) is the most abundant mammalian mRNA methylation with versatile functions. To date, although a number of bioinformatics tools have been developed for location discovery of m6A modification, functional understanding is still quite limited. As the focus of RNA epigenetics gradually shifts from site discovery to functional studies, there is an urgent need for user-friendly tools to identify and explore the functional relevance of context-specific m6A methylation to gain insights into the epitranscriptome layer of gene expression regulation. RESULTS: We introduced here Funm6AViewer, a novel platform to identify, prioritize and visualize the functional gene interaction networks mediated by dynamic m6A RNA methylation unveiled from a case control study. By taking the differential RNA methylation data and differential gene expression data, both of which can be inferred from the widely used MeRIP-seq data, as the inputs, Funm6AViewer enables a series of analysis, including: (i) examining the distribution of differential m6A sites, (ii) prioritizing the genes mediated by dynamic m6A methylation and (iii) characterizing functionally the gene regulatory networks mediated by condition-specific m6A RNA methylation. Funm6AViewer should effectively facilitate the understanding of the epitranscriptome circuitry mediated by this reversible RNA modification. AVAILABILITY AND IMPLEMENTATION: Funm6AViewer is available both as a convenient web server (https://www.xjtlu.edu.cn/biologicalsciences/funm6aviewer) with graphical interface and as an independent R package (https://github.com/NWPU-903PR/Funm6AViewer) for local usage. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

m7GHub: deciphering the location, regulation and pathogenesis of internal mRNA N7-methylguanosine (m7G) sites in human.

MOTIVATION: Recent progress in N7-methylguanosine (m7G) RNA methylation studies has focused on its internal (rather than capped) presence within mRNAs. Tens of thousands of internal mRNA m7G sites have been identified within mammalian transcriptomes, and a single resource to best share, annotate and analyze the massive m7G data generated recently are sorely needed. RESULTS: We report here m7GHub, a comprehensive online platform for deciphering the location, regulation and pathogenesis of internal mRNA m7G. The m7GHub consists of four main components, including: the first internal mRNA m7G database containing 44 058 experimentally validated internal mRNA m7G sites, a sequence-based high-accuracy predictor, the first web server for assessing the impact of mutations on m7G status, and the first database recording 1218 disease-associated genetic mutations that may function through regulation of m7G methylation. Together, m7GHub will serve as a useful resource for research on internal mRNA m7G modification. AVAILABILITY AND IMPLEMENTATION: m7GHub is freely accessible online at www.xjtlu.edu.cn/biologicalsciences/m7ghub. CONTACT: kunqi.chen@liverpool.ac.uk. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Exploring the Role of a Novel Peptide from Allomyrina dichotoma Larvae in Ameliorating Lipid Metabolism in Obesity.

The aim of this study was to identify an anti-obesity peptide from Allomyrina dichotoma and investigate the lipid metabolic mechanism. Enzymatically hydrolyzed A. dichotoma larvae were further separated using tangential flow filtration and consecutive chromatographic processes. Finally, an anti-obesity peptide that showed the highest inhibitory effect on lipid accumulation was obtained, and the sequence was Glu-Ile-Ala-Gln-Asp-Phe-Lys-Thr-Asp-Leu (EIA10). EIA10 decreased lipid aggregation in vitro and significantly reduced the accumulation of body weight gain, liver weight, and adipose tissue weight in high-fat-fed mice. Compared with the control group, the levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL), insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) in the high-fat diet (HFD) group increased significantly, and the content of high-density lipoprotein cholesterol (HDL) in the serum decreased significantly. On the contrary, the levels of TC, TG, and insulin in the EIA10 group decreased significantly, and the HDL content increased significantly compared with the HFD group. Additionally, EIA10 dramatically decreased mRNA and protein levels of transcription factors involved in lipid adipogenesis. Taken together, our results suggest that EIA10 could be a promising agent for the treatment and prevention of obesity.

Metabolomic Analysis of Morus Cultivar Root Extracts and Their Ameliorative Effect on Testosterone-Induced Prostate Enlargement in Sprague-Dawley Rats.

We investigated the metabolite changes of Morus roots (MRs) according to different cultivar families (Simheung, Daesim, Cheong-il, Sangchon, Daeseong, Suhong, Suwon, and Igsu) using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) to understand the relationship between different cultivars and metabolite changes. Data were analyzed by partial least squares discriminant analysis (PLS-DA), and samples were successfully separated in PLS-DA scores. Eight metabolites in the electrospray ionization (ESI)-positive mode and 16 metabolites in the ESI-negative mode contributed to the separation in PLS-DA. Our data suggest that comparative analysis of MR metabolites according to different cultivars is useful to better understand the relationship between the different cultivars and metabolite changes. Furthermore, we analyzed the MRs for their ability to improve benign prostatic hyperplasia (BPH). LNCaP cells were used to evaluate the prostate-specific antigen (PSA) inhibitory activity of MRs, and, amongst them, the extract with the highest activity was selected. Igsu demonstrated the highest inhibition effect of prostate-specific antigen (PSA) expression among the MR cultivars. Igsu was also evaluated by administration in a testosterone-induced benign prostatic hyperplasia model in Sprague-Dawley rats. Igsu was shown to ameliorate BPH as evidenced by the prostate index, expression of androgen receptor (AR) signaling-related protein, growth factors, cell proliferation-related proteins, apoptosis-related proteins, mitogen-activated protein kinase (MAPK) signaling proteins, and histological analysis. Hence, this study strongly suggests that Igsu may have a beneficial effect of on BPH.

Summer season temperature-humidity index threshold for infrared thermography in Hanwoo (Bos taurus coreanae) heifers.

OBJECTIVE: The study sought to estimate the relationship between body surface temperature (BST) and temperature humidity index (THI) and to present the validity of THI as a heat stress index in the field. METHODS: Eight Hanwoo heifers (20 to 32 month) were examined in a field trial, with a space allowance of 10 m2 per head. The BST was measured using an infrared thermographic camera. The BST of five body regions (eyes, hindquarters, nose, part of horns, and ears), ambient temperature (AT), and relative humidity (RH) were measured 7 times daily (07, 09, 11, 13, 15, 17, and 19 h) during each season with three replicates. RESULTS: The THI ranged 34.0 to 56.9 during spring (AT, -1.0°C to 13.4°C), 75.1 to 84.7 during summer (AT, 24.9°C to 33.6°C), 55.8 to 70.9 during autumn (AT, 13.0°C to 26.0°C) and 17.5 to 39.2 during winter (AT, -10.4°C to 1.0°C). In the regression analysis, the coefficient of determination (R2) between THI and BST was 0.88, 0.72, 0.83, 0.86, and 0.85 for the eyes, hindquarters, nose, part of horn, and ears area, respectively. This indicates that BST has a strong correlation with AT and RH. Expression equations were estimated as Y (THI) = 31.54+0.1085X (BST of eyes) and Y (THI) = 30.48+0.1147X (BST of hindquarters) by simple linear regression analysis in this experiment. CONCLUSION: Consequently, the upper bound for heat stress estimation can be specified ranging from THI of 65 (eyes) to 70 (hindquarters). From this we can expect a precise feeding system for Korean native cattle in the field.

Sika deer (Cervus nippon) velvet antler extract attenuates prostate cancer in xenograft model.

The present study determines whether antler extract (AE) possesses inhibitory effects in a prostate cancer (PC) xenograft model and explores the underlying mechanism. After therapeutic intervention for two weeks, AE significantly inhibited prostate cancer xenograft tumor growth by 65.08%, and prostate-specific antigen (PSA) and serum dihydrotestosterone (DHT) levels. However, AE increased the serum testosterone level compared to the vehicle control group. Furthermore, our investigation of the inhibitory effects on angiogenesis and epithelial-to-mesenchymal transition (EMT)-related genes revealed that AE downregulated matrix metalloproteinase 2 (MMP)-2, (MMP)-9, vascular endothelial growth factor (VEGF), zinc finger protein (SNAIL1), twist-related protein 1 (TWIST1), and zinc-finger E-box-binding homeobox 1 (ZEB1) in vivo. In contrast, AE increased tissue inhibitor of MMP (TIMP)-1, (TIMP)-2, and E-cadherin. The results suggest that AE possesses potent anti-PC activity, and this is the first report on the anti-PC effect of AE in vivo.

Effect of cinnamamides on atopic dermatitis through regulation of IL-4 in CD4+ cells.

This study aimed to evaluate the effects of cinnamamides on atopic dermatitis (AD) and the mechanisms underlying these effects. To this end, the actions of two cinnamamides, (E)-3-(4-hydroxyphenyl)-N-phenylethyl acrylamide (NCT) and N-trans-coumaroyltyramine (NCPA), were determined on AD by orally administering them to mice. Oral administration of the cinnamamides ameliorated the increase in epidermal and dermal thickness as well as mast cell infiltration. Cinnamamides suppressed serum immunoglobulin (Ig) levels and expression of T-helper (Th)1/Th2 cytokines. Moreover, cinnamamides suppressed interleukin (IL)-4, which plays a crucial role in preparing naïve clusters of differentiation (CD)4+ T cells, and decreased the cervical lymph node size and weight. Interestingly, in almost all cases, NCPA exhibited higher anti-AD activity compared to NCT. These results strongly indicate that NCPA may have potential as an anti-AD agent, and further mechanistic comparative studies of NCT and NCPA are required to determine the cause of differences in biological activity.

Investigation of the Anti-Prostate Cancer Properties of Marine-Derived Compounds.

This review focuses on marine compounds with anti-prostate cancer properties. Marine species are unique and have great potential for the discovery of anticancer drugs. Marine sources are taxonomically diverse and include bacteria, cyanobacteria, fungi, algae, and mangroves. Marine-derived compounds, including nucleotides, amides, quinones, polyethers, and peptides are biologically active compounds isolated from marine organisms such as sponges, ascidians, gorgonians, soft corals, and bryozoans, including those mentioned above. Several compound classes such as macrolides and alkaloids include drugs with anti-cancer mechanisms, such as antioxidants, anti-angiogenics, antiproliferatives, and apoptosis-inducing drugs. Despite the diversity of marine species, most marine-derived bioactive compounds have not yet been evaluated. Our objective is to explore marine compounds to identify new treatment strategies for prostate cancer. This review discusses chemically and pharmacologically diverse marine natural compounds and their sources in the context of prostate cancer drug treatment.

Fatty acid compositions, free radical scavenging activities, and antioxidative enzyme activities of high-preference and low-preference beef cuts of Hanwoo (Bos taurus coreanae) cows.

OBJECTIVE: This study compared fatty acid compositions and antioxidant activities of high-preference cuts (loin, tenderloin, and rib) and low-preference cuts (brisket, topside, and shank) of Hanwoo (Bos taurus coreanae) cows to obtain potentially useful information for promoting the consumption of various low-preference cuts. METHODS: Individual 500 g samples of fresh beef were collected from each of the six cuts from 10 Hanwoo cows (quality grade 1) and immediately freeze-dried. The dried samples were evaluated for fatty acid composition, free radical scavenging activities (hydroxyl, alkyl, and 2, 2'-diphenyl-1-picrylhydrazyl [DPPH] radical), and antioxidative enzyme activities (glutathione peroxidase [GPx], glutathione-S-transferase [GST], and superoxide dismutase [SOD]). RESULTS: The percentages of total polyunsaturated fatty acids were significantly higher in low-preference cuts than in high-preference cuts (p<0.05). Hydroxyl, alkyl, and DPPH radical scavenging activities were significantly higher in low-preference cuts than in high-preference cuts (p<0.05). In addition, the activities of antioxidant enzymes, such as GPx, GST, and SOD, were significantly higher in low-preference cuts compared with high-preference cuts (p<0.05). CONCLUSION: These results may influence consumers to include more low-preference cuts in their selections based on the nutritional facts, which could help to balance the beef market in South Korea.

Taurine Attenuates Epithelial-Mesenchymal Transition-Related Genes in Human Prostate Cancer Cells.

Prostate cancer is the most common non-cutaneous cancers among men and the second leading cause of cancer-related deaths among men. Aberrant activation of the epithelial to mesenchymal transition (EMT) has been exhibited to be one of the most common causes of treatment failure and death in cancer patients. In cancer cells with metastatic competence, the E-cadherin switch is a well-established hallmark. Suppression of E-cadherin through its transcriptional repressor SNAIL is thus a determining factor for EMT. TWIST1 is an important transcription factor in EMT, which is present under both physiologic (embryogenesis) and pathologic (metastasis) conditions, and enhances the invasiveness and migration ability of cells. In this study, we investigated the inhibitory effects of taurine on EMT-related genes, such as E-cadherin, N-cadherin, TWIST1, ZEB1, SNAIL, and vimentin. EMT markers were detected by RT-PCR and western blotting. The results showed that taurine down-regulated the expression of N-cadherin, TWIST1, ZEB1, SNAIL, and vimentin. In contrast, taurine increased E-cadherin expression. Our findings indicate that taurine has EMT inhibitory effects on human prostate cancer cells.

Protective Effect of Taurine on Mice with Doxorubicin-induced Acute Kidney Injury.

Nephrotic syndrome is still a therapeutic challenge because an effective treatment has not been developed. Evidence suggests that multidrug therapy is more effective than monotherapy in amelioration of renal injury. Therefore, we examined if taurine exerts a protective effect on doxorubicin-induced acute kidney injury in mice. Eight-week-old male Balb/c nude mice were used in this study. Taurine was orally administered at a dose of 50 mg/kg and 100 mg/kg body weight for 5 days. In the meantime, the mice were administered intraperitoneal injections of doxorubicin at 15 mg/kg body weight. At 24 h after the doxorubicin challenge, the response in the taurine-treated mice was compared with that in the vehicle-treated control mice. The doxorubicin-induced acute kidney injury model displayed a significant increase in the renal expression of apoptosis-related proteins (p53, phospho-p53, caspase 9, and caspase 3), whereas in the taurine-treated mice, the augmented expression of renal inflammation-related mRNAs such as NF-kB, COX-2, and iNOS was down-regulated. These results suggest that taurine acts as a renoprotective agent by inhibiting apoptosis and inflammation in the kidney of mice with doxorubicin-induced renal injury.

First evidence that Ecklonia cava-derived dieckol attenuates MCF-7 human breast carcinoma cell migration.

We investigated the effect of Ecklonia cava (E. cava)-derived dieckol on movement behavior and the expression of migration-related genes in MCF-7 human breast cancer cell. Phlorotannins (e.g., dieckol, 6,6'-biecko, and 2,7″-phloroglucinol-6,6'-bieckol) were purified from E. cava by using centrifugal partition chromatography. Among the phlorotannins, we found that dieckol inhibited breast cancer cell the most and was selected for further study. Radius™-well was used to assess cell migration, and dieckol (1-100 µM) was found to suppress breast cancer cell movement. Metastasis-related gene expressions were evaluated by RT-PCR and Western blot analysis. In addition, dieckol inhibited the expression of migration-related genes such as matrix metalloproteinase (MMP)-9 and vascular endothelial growth factor (VEGF). On the other hand, it stimulated the expression of tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2. These results suggest that dieckol exerts anti-breast cancer activity via the regulation of the expressions of metastasis-related genes, and this is the first report on the anti-breast cancer effect of dieckol.

[Epidemiologic investigation of cardiac arrest and current research status on its risk factors analysis].

Cardiac arrest most commonly occurs outside of the hospital, known as out-of-hospital cardiac arrest (OHCA), and is an important global health problem. Approximately 40% of cardiac arrest has no clear cause. Hereditary arrhythmias and cardiomyopathies factors contribute to cardiac arrest. The identification of genetic factors for cardiac arrest after its occurrence is of great value not only for the individual, but also for relatives who may be at risk for the disease in their family. In the United States, there are over 350 000 cases of OHCA and over 200 000 cases of in-hospital cardiac arrest (IHCA) each year, and in Western Europe, cardiac arrest accounts for 15%-20% of all adult natural deaths and 50% of all cardiovascular deaths. In order to reduce the burden caused by cardiac arrest within society, it is essential to further understand its etiological factors, such as incidence in different regions, risk factors, and populations at higher risk. For each individual, cardiac arrest is the result of a complex interaction of genetic and acquired factors. Understanding the complex interplay of pathogenic factors in cardiac arrest and the development of individualized prevention and treatment approaches requires the collection of clinical data from cardiac arrest populations and multimodal analysis in order to identify epidemiological features and risk factors for cardiac arrest. Recently, cardiac arrest-related data are being collected and integrated in Europe in different regions and populations. As a result of the commitment to the creation of large datasets of clinical information on cardiac arrest populations, the knowledge of the pathology of cardiac arrest pathogenesis as well as risk factors is steadily increasing. This article reviews the epidemiologic data of cardiac arrest in recent years and the associated risk factors, thus providing ideas for developing better strategies for the prevention and treatment of cardiac arrest.

Protective Effect of Deer Heart Peptide on Cardiac Injury in Mice.

Peptides are widely used as natural bio-small molecules because of their various pharmacological activities such as enhancing immunity, promoting wound healing, and improving inflammation. Alcoholic heart injury has become one of the major health problems worldwide, and alcohol consumption is now the main cause of alcoholic cardiomyopathy. In this study, deer heart peptides were extracted from deer hearts by enzymatic digestion and the antioxidant activity of deer heart peptides extracted at different times was evaluated by three in vitro antioxidant methods, and the active peptide with the best enzymatic effect has been selected for in vivo animal experiments. The anti-inflammatory and antioxidant properties of deer heart enzymatic extracts were evaluated in in vivo experiments in mice. In this study, mice were orally gavaged with white wine (12 mL/kg body weight) to induce a mouse model of cardiac injury, while mice were orally administered a single dose of 100 mg/kg/bw and 200 mg/kg/bw of deer heart enzyme digest and were examined for body weight, dietary intake, water intake, and coat gloss, as well as for general behaviors, adverse effects, and mortality. Histology, serum, anti-inflammatory factors, and oxidative stress parameters were subsequently assessed. In all modeled mice, no four-way or any significant behavioral changes were observed in all groups, but in the modeled group, mice showed weight loss, decreased diet and water intake, and decreased cardiac index. For in vivo tests, the extract inhibited the anti-inflammatory activity with a significant decrease in inflammatory factors of TNF-α, IL-6, and IL-1ß in cardiac tissues, a significant increase in serum levels of both CAT and SOD, an increase in MDA content, and a remarkable increase in the level of the marker CK in the cardiac myocardial enzyme profile. Significant improvement in myocardial disorders by deer heart peptide could be observed from heart tissue sections. The present study emphasizes the anti-inflammatory and antioxidant activity of deer heart peptide, an enzymatic digest of deer heart, which provides empirical as well as supportive role for the anti-inflammatory properties of traditional medicine.

Long Noncoding RNA SOX2OT Ameliorates Sepsis-Induced Myocardial Injury by Inhibiting Cellular Pyroptosis Through Mediating the EZH2/Nrf-2/NLRP3 Signaling Pathway.

Objective: Cellular pyroptosis is a pro-inflammatory mode of programmed cell death that has been identified in recent years, and studies have shown that the LncRNA SOX2OT regulates myocardial injury during sepsis, but the exact regulatory mechanism is unclear. The aim of this study was to assess the role of SOX2OT in regulating cardiomyocyte injury during sepsis cardiomyopathy. Methods: Rat cardiomyocytes, C57BL/6 mice, and transgenic mice were divided into four groups: control, LPS, LPS+ knockout LncRNA SOX2OT, and LPS+ overexpression LncRNA SOX2OT. Inflammatory factor levels were detected by qPCR. Associated proteins and gene expression were detected by Western blotting and qPCR. Dual luciferase was used to detect the target genes of SOX2OT. Nrf2 and EZH2 knockdown and overexpression cell lines were established, and the expression of related genes was detected by qPCR. Results: Results In this study, we found that SOX2OT knockdown exacerbated LPS-induced levels of inflammatory factors and procalcitoninogen (PCT), and increased the expression of pyroptosis-related proteins and LDH. The results of dual luciferase reporter gene assay showed that EZH2 is the target gene of SOX2OT, and overexpression of SOX2OT decreased the expression of EZH2; we also found that knockdown of EZH2 in H9c2 cells decreased the expression of Nrf2, which was positively correlated with the expression level of NLRP3. Further in vivo results showed that overexpression of SOX2OT attenuated SIMD (sepsis-induced myocardial dysfunction), as evidenced by improved myocardial structural integrity and reduced inflammatory cell infiltration. The expression of pyroptosis-related proteins and LDH was significantly increased in the mice in the LPS group; this effect was reversed by overexpression of SOX2OT, and potentiated by knockdown of SOX2OT. Conclusion: Our data reveal a novel mechanism by which SOX2OT inhibits cardiomyocyte sepsis through the EZH2/Nrf-2/NLRP3 pathway, thereby attenuating septic myocardial injury, which may contribute to the development of new therapeutic strategies.

Polyhydroxy structure orchestrates the intrinsic antibacterial property of acrylamide hydrogel as a versatile wound-healing dressing.

Hydrogel is considered as a promising candidate for wound dressing due to its tissue-like flexibility, good mechanical properties and biocompatibility. However, traditional hydrogel dressings often fail to fulfill satisfied mechanical, antibacterial, and biocompatibility properties simultaneously, due to the insufficient intrinsic bactericidal efficacy and the addition of external antimicrobial agents. In this paper, hydroxyl-contained acrylamide monomers, N-Methylolacrylamide (NMA) and N-[Tris (hydroxymethyl)methyl] acrylamide (THMA), are employed to prepare a series of polyacrylamide hydrogel dressings xNMA-yTHMA, where x and y represent the mass fractions of NMA and THMA in the hydrogels. We have elucidated that the abundance of hydroxyl groups determines the antibacterial effect of the hydrogels. Particularly, hydrogel 35NMA-5THMA exhibits excellent mechanical properties, with high tensile strength of 259 kPa and large tensile strain of 1737%. Furthermore, the hydrogel dressing 35NMA-5THMA demonstrates remarkable inherent antibacterial without exogenous antimicrobial agents owing to the existence of abundant hydroxyl groups. Besides, hydrogel dressing 35NMA-5THMA possesses excellent biocompatibility, in view of marginal cytotoxicity, low hemolysis ratio, and negligible inflammatory response and organ toxicity to mice during treatment. Encouragingly, hydrogel 35NMA-5THMA drastically promote the healing of bacteria-infected wound in mice. This study has revealed the importance of polyhydroxyl in the antibacterial efficiency of hydrogels and provided a simplified strategy to design wound healing dressings with translational potential.