Identification of a novel native peptide derived from 60S ribosomal protein L23a that translationally regulates p53 to reduce myocardial ischemia-reperfusion.

Myocardial ischemia-reperfusion (I/R) is a severe disease，but its underlying mechanism is not fully elucidated and no effective clinical treatment is available. Utilizing intracellular peptidomics, we identified a novel native peptide PDRL23A (Peptide Derived from RPL23A), that is intimately related to hypoxic stress. We further show that PDRL23A effectively alleviates hypoxia-induced cardiomyocyte injury in vitro, along with improvements in mitochondrial function and redox homeostasis, including ROS accumulation, oxidative phosphorylation, and mitochondrial membrane potential. Strikingly, the in vivo results indicate that, short-term pretreatment with PDRL23A could effectively inhibit I/R-induced cardiomyocyte death, myocardial fibrosis and decreased cardiac function. Interestingly, PDRL23A was found to interact with 60 S ribosomal protein L26 (RPL26), hampering RPL26-governed p53 translation, and resulting in a reduction in the level of p53 protein, which in turn reduced p53-mediated apoptosis under hypoxic conditions. Collectively, a native peptide, PDRL23A, which translationally regulates p53 to protect against myocardial I/R injury, has been identified for the first time. Our findings provide insight into the adaptive mechanisms of hypoxia and present a potential new treatment for myocardial I/R.

Exercise-induced peptide EIP-22 protect myocardial from ischaemia/reperfusion injury via activating JAK2/STAT3 signalling pathway.

Recent studies have revealed that exercise has myocardial protective effects, but the exact mechanism remains unclear. Studies have increasingly found that peptides play a protective role in myocardial ischaemia-reperfusion (I/R) injury. However, little is known about the role of exercise-induced peptides in myocardial I/R injury. To elucidate the effect of exercise-induced peptide EIP-22 in myocardial I/R injury, we first determined the effect of EIP-22 on hypoxia/reperfusion (H/R)- or H2 O2 -induced injury via assessing cell viability and lactate dehydrogenase (LDH) level. In addition, reactive oxygen species (ROS) accumulation and mitochondrial membrane potential (MMP) was assessed by fluorescence microscope. Meanwhile, Western blot and TUNEL methods were used to detect apoptosis level. Then, we conducted mice I/R injury model and verified the effect of EIP-22 by measuring cardiac function, evaluating heart pathology and detecting serum LDH, CK-MB and cTnI level. Finally, the main signalling pathway was analysed by RNA-seq. In vitro, EIP-22 treatment significantly improved cells viabilities and MMP and attenuated the LDH, ROS and apoptosis level. In vivo, EIP-22 distinctly improved cardiac function, ameliorated myocardial infarction area and fibrosis and decreased serum LDH, CK-MB and cTnI level. Mechanistically, JAK/STAT signalling pathway was focussed by RNA-seq and we confirmed that EIP-22 up-regulated the expression of p-JAK2 and p-STAT3. Moreover, AG490, a selective inhibitor of JAK2/STAT3, eliminated the protective roles of EIP-22. The results uncovered that exercise-induced peptide EIP-22 protected cardiomyocytes from myocardial I/R injury via activating JAK2/STAT3 signalling pathway and might be a new candidate molecule for the treatment of myocardial I/R injury.

Exercise-induced peptide TAG-23 protects cardiomyocytes from reperfusion injury through regulating PKG-cCbl interaction.

Recent studies have revealed that proper exercise can reduce the risk of chronic disease and is beneficial to the body. Peptides have been shown to play an important role in various pathological processes, including cardiovascular diseases. However, little is known about the role of exercise-induced peptides in cardiovascular disease. We aimed to explore the function and mechanism of TAG-23 peptide in reperfusion injury and oxidative stress. Treatment with TAG-23 peptide significantly improved cell viability, the mitochondrial membrane potential, and ROS levels and reduced LDH release, the apoptosis rate and caspase 3 activation in vitro. In vivo, TAG-23 ameliorated MI and heart failure induced by I/R or DOX treatment. Pull-down assays showed that TAG-23 can bind to PKG . The TAG-23-PKG complex inhibited PKG degradation through the UPS. We also identified cCbl as the E3 ligase of PKG and found that the interaction between these proteins was impaired by TAG-23 treatment. In addition, we provided evidence that TAG-23 mediated Lys48-linked polyubiquitination and subsequent proteasomal degradation. Our results reveal that a novel exercise-induced peptide, TAG-23, can inhibit PKG degradation by serving as a competitive binding peptide to attenuate the formation of the PKG-cCbl complex. Treatment with TAG-23 may be a new therapeutic approach for reperfusion injury.

Long noncoding RNA uc.4 inhibits cell differentiation in heart development by altering DNA methylation.

In previous studies, we have demonstrated that long noncoding RNA uc.4 may influence the cell differentiation through the TGF-ß signaling pathway, suppressed the heart development of zebrafish and resulting cardiac malformation. DNA methylation plays a significant role in the heart development and disordered of DNA methylation may cause disruption of control of gene promoter. In this study, methylated DNA immunoprecipitation was performed to identify the different expression levels of methylation regions. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were also performed to identify the possible biological process and pathway that uc.4 may join, associated with Rap1 signaling pathway, gonadotropin-releasing hormone signaling pathway, and Calcium signaling pathway. We found that the distribution of differentially methylated regions peaks was mainly located in intergenic and intron regions. Altogether, our result showed that differentially methylated genes are significantly expressed in uc.4-overexpression cells, providing valuable data for further exploration of the role of uc.4 in heart development.

Relationship between time-weighted average glucose and mortality in critically ill patients: a retrospective analysis of the MIMIC-IV database.

Blood glucose management in intensive care units (ICU) remains a controversial topic. We assessed the association between time-weighted average glucose (TWAG) levels and ICU mortality in critically ill patients in a real-world study. This retrospective study included critically ill patients from the Medical Information Mart for Intensive Care IV database. Glycemic distance is the difference between TWAG in the ICU and preadmission usual glycemia assessed with glycated hemoglobin at ICU admission. The TWAG and glycemic distance were divided into 4 groups and 3 groups, and their associations with ICU mortality risk were evaluated using multivariate logistic regression. Restricted cubic splines were used to explore the non-linear relationship. A total of 4737 adult patients were included. After adjusting for covariates, compared with TWAG ≤ 110 mg/dL, the odds ratios (ORs) of the TWAG > 110 mg/dL groups were 1.62 (95% CI 0.97-2.84, p = 0.075), 3.41 (95% CI 1.97-6.15, p < 0.05), and 6.62 (95% CI 3.6-12.6, p < 0.05). Compared with glycemic distance at - 15.1-20.1 mg/dL, the ORs of lower or higher groups were 0.78 (95% CI 0.50-1.21, p = 0.3) and 2.84 (95% CI 2.12-3.82, p < 0.05). The effect of hyperglycemia on ICU mortality was more pronounced in non-diabetic and non-septic patients. TWAG showed a U-shaped relationship with ICU mortality risk, and the mortality risk was minimal at 111 mg/dL. Maintaining glycemic distance ≤ 20.1 mg/dL may be beneficial. In different subgroups, the impact of hyperglycemia varied.

Clinical Characteristics and Risk Factors for Infection and Death in Critically Ill Patients with Pulmonary Infection with Elizabethkingia Spp.

Purpose: Elizabethkingia spp. infections have recently increased, and they are difficult to treat because of intrinsic antimicrobial resistance. This study aimed to investigate the clinical characteristics of patients with pulmonary infection with Elizabethkingia spp. and reveal the risk factors for infection and death. Patients and Methods: In this retrospective case-control study, patients were divided into infection and control groups based on the bacterial identification results. Patients in the infection group were further divided into survival and death groups according to their hospital outcomes. Clinical characteristics between different groups were compared. We further analyzed antimicrobial susceptibility testing results of the isolated strains. Results: A total of the 316 patients were divided into infection (n = 79), 23 of whom died, and control (n = 237) groups. Multivariate logistic regression analysis showed that glucocorticoid consumption (OR: 2.35; 95% CI: 1.14-4.81; P = 0.02), endotracheal intubation (OR: 3.74; 95% CI: 1.62-8.64; P = 0.002), and colistin exposure (OR: 2.50; 95% CI: 1.01-6.29; P = 0.046) were significantly associated with pulmonary infection with Elizabethkingia spp. Advanced age (OR: 1.07, 95% CI: 1.00-1.15; P = 0.046), high acute physiology and chronic health evaluation (APACHE) II score (OR: 1.21; 95% CI: 1.01-1.45; P = 0.037), and low albumin level (OR: 0.73, 95% CI: 0.56-0.96; P = 0.025) were significantly associated with in-hospital mortality of infected patients. Elizabethkingia spp. was highly resistant to cephalosporins, carbapenems, macrolides, and aminoglycoside, and was sensitive to fluoroquinolones, minocycline, and co-trimoxazole in vitro. Conclusion: Glucocorticoid consumption, tracheal intubation, and colistin exposure were associated with pulmonary infection with Elizabethkingia spp. for critically ill patients. Patients with advanced age, high APACHE II score, and low albumin level had higher risk of death from infection.

Peptide PDRPS6 attenuates myocardial ischemia injury by improving mitochondrial function.

Mitochondrial dynamics play a crucial role in myocardial ischemia-reperfusion (I/R) injury, where an imbalance between fusion and fission processes occurs. However, effective measures to regulate mitochondrial dynamics in this context are currently lacking. Peptide derived from the 40 S ribosomal protein S6 (PDRPS6), a peptide identified via peptidomics, is associated with hypoxic stress. This study aimed to investigate the function and mechanism of action of PDRPS6 in I/R injury. In vivo, PDRPS6 ameliorated myocardial tissue injury and cardiomyocyte apoptosis and decreased cardiac function induced by I/R injury in rats. PDRPS6 supplementation significantly reduced apoptosis in vitro. Mechanistically, PDRPS6 improved mitochondrial function by decreasing reactive oxygen species (ROS) levels, maintaining mitochondrial membrane potential (MMP), and inhibiting mitochondrial fission. Pull-down assay analyses revealed that phosphoglycerate mutase 5 (PGAM5) may be the target of PDRPS6, which can lead to the dephosphorylation of dynamin-related protein1 (Drp1) at ser616 site. Overexpression of PGAM5 partially eliminated the effect of PDRPS6 on improving mitochondrial function. These findings suggest that PDRPS6 supplementation is a novel method for treating myocardial injuries caused by I/R.

Research Note: Effect of different photoperiodic programs from rearing period on the reproductive performance and hormone secretion of White King pigeons.

The photoperiod is an important factor during rearing and laying period that affects age and body weight at sexual maturation and reproductive performance in poultry; however relevant research on this factor in pigeons is still lacking. Thus, this study investigated the effects of different photoperiodic programs on the reproductive performance and hormonal profile in White King pigeons. From 101 d of age, the pigeons in the control group were exposed to a natural photoperiod until 160 d, and then to a photoperiod of 16 h (16 light [L]: 8 dark [D]) and lasted for 200 d. Pigeons in the 3 experimental groups were exposed to a short photoperiod of 8L: 16D until 160 d, and then to 14L: 10D, 16L: 8D, and 18L: 6D, respectively. The results showed that light-restriction (8L: 16D) during the rearing period and then 14L: 10D or 16L: 8D photostimulation delayed the age at first egg laying in pigeons. However, 16L: 8D after an 8L: 16D photoperiod during the breeding period ensured maximum photosensitivity, and significantly improved the reproductive performance (egg production and fertility rates) in pigeons. Moreover, the highest reproductive performance in group under16L: 8D after 8L: 16D photoperiodic program was accompanied by improved follicle-stimulating hormone and estradiol levels and reduced prolactin hormone levels. The results indicated that photoperiodic programs from rearing to laying period are closely related to the reproductive performance of White King pigeons. The results provide information that 8L: 16D during rearing period and 16L: 8D during laying period can be used to enhance reproductive performance in the pigeon industry.

Effects of sex on meat quality traits, amino acid and fatty acid compositions, and plasma metabolome profiles in White King squabs.

The objective of this study was to investigate the effects of sex on meat quality and the composition of amino and fatty acids in the breast muscles of White King pigeon squabs. Untargeted metabolomics was also conducted to distinguish the metabolic composition of plasma in different sexes. Compared with male squabs, female squabs had greater intramuscular fat (IMF) deposition and lower myofiber diameter and hydroxyproline content, leading to a lower shear force. Female squabs also had higher monounsaturated fatty acid and lower n-6 and n-3 polyunsaturated fatty acid proportions in the breast muscle, and had greater lipogenesis capacity via upregulation of PPARγ, FAS and LPL gene expression. Moreover, female squabs had lower inosine 5'-monophosphate, essential, free and sweet-tasting amino acid contents. Furthermore, Spearman's correlations between the differential plasma metabolites and key meat parameters were assessed, and putrescine, N-acetylglutamic acid, phophatidylcholine (18:0/P-16:0) and trimethylamine N-oxide were found to contribute to meat quality. In summary, the breast meat of male squabs may have better nutritional value than that of females, but it may inferior in terms of sensory properties, which can be attributed to the lower IMF content and higher shear force value. Our findings enhance our understanding of sex variation in squab meat quality, providing a basis for future research on pigeon breeding.

A novel peptide HSP-17 ameliorates oxidative stress injury and apoptosis in H9c2 cardiomyocytes by activating the PI3K/Akt pathway.

Background: Oxidative stress and cell apoptosis play pivotal roles in the pathogenesis of doxorubicin (DOX)-induced myocardial injury. Heat shock protein-derived peptide (HSP-17) is a peptide which is low-expressed in DOX treated mouse heart tissue. It has high bioactivity and interspecies sequence consistency, and is predicted to have myocardial protective effect. Methods: Firstly, we added 1 µM DOX to H9c2 cell culture medium for 24 hours to construct the myocardial cytotoxicity model. Then we detected the effect of HSP-17 on DOX induced H9c2 cardiomyocyte injury by measuring cell viability and lactate dehydrogenase (LDH) level. In addition, reactive oxygen species (ROS) and tetraethylbenzimidazolylcarbocyanine iodide kits are used to evaluate the effect of the HSP-17 peptide on DOX-induced oxidative stress injury to cardiomyocytes, and the detection of apoptosis related proteins and flow cytometry were applied to detect the level of apoptosis. Furthermore, the protein expression levels [phosphorylated Akt (p-Akt) and phosphorylated PI3K (p-PI3K)] of the PI3K/Akt pathway were also detected by western blotting. Results: We found that the HSP-17 peptide can increase cell viability, protect mitochondrial potential, reduce LDH levels, and reduce ROS and cardiomyocyte apoptosis. In addition, we also observed that HSP-17 upregulated the expression level of p-Akt, and LY294002, a typical inhibitor of PI3K/Akt, was found to eliminate the protective roles of HSP-17. Conclusions: In conclusion, this study demonstrated that the HSP-17 peptide protected H9c2 cells against oxidative stress and apoptosis via PI3K/Akt pathway activation, which provides a new idea for the treatment of DOX-induced myocardial injury.

ELA-11 protects the heart against oxidative stress injury induced apoptosis through ERK/MAPK and PI3K/AKT signaling pathways.

Increasing evidence revealed that apoptosis and oxidative stress injury were associated with the pathophysiology of doxorubicin (DOX)-induced myocardial injury. ELABELA (ELA) is a newly identified peptide with 32 amino acids, can reduce hypertension with exogenous infusion. However, the effect of 11-residue furn-cleaved fragment (ELA-11) is still unclear. We first administrated ELA-11 in DOX-injured mice and measured the cardiac function and investigated the effect of ELA-11 in vivo. We found that ELA-11 alleviated heart injury induced by DOX and inhibited cardiac tissues from apoptosis. In vitro, ELA-11 regulated the sensitivity towards apoptosis induced by oxidative stress with DOX treatment through PI3K/AKT and ERK/MAPK signaling pathway. Similarly, ELA-11 inhibited oxidative stress-induced apoptosis in cobalt chloride (CoCl2)-injured cardiomyocytes. Moreover, ELA-11 protected cardiomyocyte by interacting with Apelin receptor (APJ) by using 4-oxo-6-((pyrimidin-2-ylthio) methyl)-4H-pyran-3-yl 4-nitrobenzoate (ML221). Hence, our results indicated a protective role of ELA-11 in oxidative stress-induced apoptosis in DOX-induced myocardial injury.

Peptide Szeto­Schiller 31 ameliorates doxorubicin­induced cardiotoxicity by inhibiting the activation of the p38 MAPK signaling pathway.

Oxidative stress serves a key role in doxorubicin (DOX)­induced cardiotoxicity. The peptide Szeto­Schiller (SS)31 is an efficacious antioxidant with the capacity to reduce mitochondrial reactive oxygen species (ROS) levels and scavenge free radicals. Although SS31 is involved in the pathophysiological process of various cardiovascular diseases, the role of SS31 in DOX­induced cardiotoxicity remains unclear. To explore the effects of SS31 in DOX­induced cardiotoxicity, the present study first constructed DOX­induced cardiotoxicity models, in which H9c2 cells were incubated with 1 µM DOX for 24 h and C57BL/6 mice were administered DOX (20 mg/kg cumulative dose). The results of various assays in these models demonstrated that SS31 exhibited a cardioprotective effect in vitro and in vivo by attenuating the level of ROS, stabilizing the mitochondrial membrane potential and ameliorating myocardial apoptosis as well as fibrosis following treatment with DOX. Mechanistically, the results of the present study revealed that the p38 MAPK signaling pathway was inhibited by SS31 in DOX­treated H9c2 cells, which was associated with the cardioprotective function of SS31. In addition, P79350, a selective agonist of p38 MAPK, reversed the protective effects of SS31. Taken together, these results demonstrated the effects of SS31 on ameliorating DOX­induced cardiotoxicity and indicated its potential as a drug for the treatment of DOX­induced cardiotoxicity.

Circular RNA Arhgap12 modulates doxorubicin-induced cardiotoxicity by sponging miR-135a-5p.

AIM: This study aimed to investigate the regulatory role of differentially-expressed circular RNAs (circRNAs) in mouse cardiomyocytes during doxorubicin (DOX)-induced cardiotoxicity. MAIN METHODS: Two groups of mice were injected with equal volumes (0.1 mL) of normal saline and DOX. Mouse heart tissue was isolated and digested for total RNA extraction and then subjected to next-generation RNA-sequencing. Expression profiles of circRNAs and circRNA-miRNA-mRNA networks were also constructed. Overall, 48 upregulated and 16 downregulated circRNAs were found to be statistically significant (p < 0.05) in the DOX-injected group. Bioinformatics analysis revealed several potential biological pathways that might be related to apoptosis caused by DOX-induced cardiotoxicity. In addition, using qRT-PCR, we found that a circRNA coded by the Arhgap12 gene, termed circArhgap12, was upregulated in the mouse heart tissue upon DOX intervention. CircArhgap12 enhanced apoptotic cell rate, as assessed using terminal-deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay, and increased reactive oxygen species and malondialdehyde release as well as superoxide dismutase and caspase-3 activation. Using a luciferase reporter assay, we found that circArhgap12 could sponge miR-135a-5p. In rat primary cardiomyocytes, we found that si-circArhgap12 promoted apoptosis and oxidative stress by sponging the miR-135a-5p inhibitor. Using bioinformatics analysis and luciferase reporter assay, we found that miR-135a-5p might have a potential target site for ADCY1 mRNA. KEY FINDINGS: Our research demonstrated that the expression profile of circRNAs was modified significantly and that circArhgap12 might play a competitive role among endogenous RNAs in mouse cardiomyocytes during DOX-induced cardiotoxicity. SIGNIFICANCE: Our study may provide a preliminary understanding of DOX-induced cardiotoxicity modulated by circRNA and its competing endogenous RNAs network.

Peptidomics Analysis Reveals Peptide PDCryab1 Inhibits Doxorubicin-Induced Cardiotoxicity.

Doxorubicin (DOX) is limited due to dose-dependent cardiotoxicity. Peptidomics is an emerging field of proteomics that has attracted much attention because it can be used to study the composition and content of endogenous peptides in various organisms. Endogenous peptides participate in various biological processes and are important sources of candidates for drug development. To explore peptide changes related to DOX-induced cardiotoxicity and to find peptides with cardioprotective function, we compared the expression profiles of peptides in the hearts of DOX-treated and control mice by mass spectrometry. The results showed that 236 differential peptides were identified upon DOX treatment, of which 22 were upregulated and 214 were downregulated. Next, we predicted that 31 peptides may have cardioprotective function by conducting bioinformatics analysis on the domains of each precursor protein, the predicted score of peptide biological activity, and the correlation of each peptide with cardiac events. Finally, we verified that a peptide (SPFYLRPPSF) from Cryab can inhibit cardiomyocyte apoptosis, reduce the production of reactive oxygen species, improve cardiac function, and ameliorate myocardial fibrosis in vitro and vivo. In conclusion, our results showed that the expression profiles of peptides in cardiac tissue change significantly upon DOX treatment and that these differentially expressed peptides have potential cardioprotective functions. Our study suggests a new direction for the treatment of DOX-induced cardiotoxicity.

Expression profile of long non­coding RNAs in cardiomyocytes exposed to acute ischemic hypoxia.

Acute myocardial infarction (AMI) is a life­threatening disease and seriously influences patient quality of life. Long non­coding RNAs (lncRNAs), an emerging class of non­coding genes, have attracted attention in research, however, whether lncRNAs serve a function in acute ischemic hypoxia remains to be elucidated. In the present study, an lncRNA microarray was used to analyze differential lncRNA expression in acute ischemic hypoxia. A total of 323 lncRNAs were identified, 168 of which were upregulated and 155 of which were downregulated. Gene Ontology and Pathway analyses were also used to identify the potential functions of dysregulated lncRNAs; it was predicted that these dysregulated lncRNAs may contribute to the initiation of AMI. It was demonstrated that an lncRNA termed sloyfley may influence acute ischemic hypoxia through its neighboring gene Peg3, which has been linked to brain ischemia hypoxia. In summary, the present study identified numerous lncRNAs, which may provide further opportunities for the development of novel therapeutic strategies.

Altered DNA Methylation of Long Noncoding RNA uc.167 Inhibits Cell Differentiation in Heart Development.

In previous studies, we have demonstrated the function of uc.167 in the heart development. DNA methylation plays a crucial role in regulating the expression of developmental genes during embryonic development. In this study, the methylomic landscape was investigated in order to identify the DNA methylation alterations. Methylated DNA immunoprecipitation (MeDIP) was performed to examine the differences in methylation status of overexpressed uc.167 in P19 cells. GO and KEGG pathway analyses of differentially methylated genes were also conducted. We found that the distribution of differentially methylated regions (DMRs) peaks in different components of genome was mainly located in intergenic regions and intron. The biological process associated with uc.167 was focal adhesion and Rap1 signaling pathway. MEF2C was significantly decreased in uc.167 overexpressed group, suggesting that uc.167 may influence the P19 differentiation through MEF2C reduction. Taken together, our findings revealed that the effect of uc.167 on P19 differentiation may be attributed to the altered methylation of specific genes.

Attenuation of Na/K-ATPase/Src/ROS amplification signal pathway with pNaktide ameliorates myocardial ischemia-reperfusion injury.

OBJECTIVES: Oxidative stress plays an important role in myocardial ischemia-reperfusion (I/R) injury. And pNaKtide is known to inhibit Na/K-ATPase/Src/reactive oxygen species (ROS) amplification signaling. Accordingly, we aimed to investigate the effect of pNaKtide on myocardial I/R injury. METHODS: We first determine the effect of pNaKtide on hypoxia- or cobalt chloride-induced injury in embryonic heart-derived H9c2 cells via measuring lactate dehydrogenase (LDH) level and trypan blue stain assay. In addition, TUNEL stain assay and western blot analysis of cleaved-PARP and cleaved-caspase3 were performed to detect apoptosis level. Meanwhile, ROS accumulation was assessed by dichlorofluorescin diacetate (DCFH-DA) assay. Then we conducted cell counting kit-8 (CCK-8) and flow cytometry to examine cell proliferation and cell cycle respectively. We next generated rat I/R model and determined the effect of pNaKtide by measuring serum LDH and evaluating heart pathology. At last, the activities of Src and ERK1/2 were examined via western blot to clarify molecular mechanism. RESULTS: In vitro, pNaKtide exposure significantly attenuated the H9c2 cells death and ROS accumulation induced by hypoxia or cobalt chloride. And no significant effect was detected on cell cycle and proliferation upon pNaKtide administration. In vivo, pNaKtide distinctly decreased serum LDH level and ameliorated I/R induced myocardial injury in the rats. Western blot analysis revealed pNaKtide decreased Src and ERK1/2 activities robustly. CONCLUSIONS: The results provided evidence that pNaKtide exhibited cardioprotective effect against hypoxia-induced injury in vitro and in vivo. And pNaKtide might be a potential molecular for therapy of I/R related heart disease.

The long non-coding RNA uc.4 influences cell differentiation through the TGF-beta signaling pathway.

In a previous study, we screened thousands of long non-coding RNAs (lncRNAs) to assess their potential relationship with congenital heart disease (CHD). In this study, uc.4 attracted our attention because of its high level of evolutionary conservation and its antisense orientation to the CASZ1 gene, which is vital for heart development. We explored the function of uc.4 in cells and in zebrafish, and describe a potential mechanism of action. P19 cells were used to investigate the function of uc.4. We studied the effect of uc.4 overexpression on heart development in zebrafish. The overexpression of uc.4 influenced cell differentiation by inhibiting the TGF-beta signaling pathway and suppressed heart development in zebrafish, resulting in cardiac malformation. Taken together, our findings show that uc.4 is involved in heart development, thus providing a potential therapeutic target for CHD.