Mesenchymal stem cell-derived exosomes in myocardial infarction: Therapeutic potential and application.

Myocardial infarction refers to the irreversible impairment of cardiac function resulting from the permanent loss of numerous cardiomyocytes and the formation of scar tissue. This condition is caused by acute and persistent inadequate blood supply to the heart's arteries. In the treatment of myocardial infarction, Mesenchymal stem cells (MSCs) play a crucial role because of their powerful therapeutic effects. These effects primarily stem from the paracrine secretion of multiple factors by MSCs, with exosome-carried microRNAs being the most effective component in promoting cardiac function recovery after infarction. Exosome therapy has emerged as a promising cell-free treatment for myocardial infarction as a result of its relatively simple composition, low immunogenicity and controlled transplantation dose. Despite these advantages, maintaining the stability of exosomes after transplantation and enhancing their targeting effect remain significant challenges in clinical applications. In recent developments, several approaches have been designed to optimize exosome therapy. These include enhancing exosome retention, improving their ability to target specific effects, pretreating MSC-derived exosomes and employing transgenic MSC-derived exosomes. This review primarily focuses on describing the biological characteristics of exosomes, their therapeutic potential and their application in treating myocardial infarction.

N6-methyladenosine functions and its role in skin cancer.

N6-methyladenosine (m6A) methylation is the most abundant mammalian mRNA modification. m6A regulates RNA processing, splicing, nucleation, translation and stability by transferring, removing and recognizing m6A methylation sites, which are critical for cancer initiation, progression, metabolism and metastasis. m6A is involved in pathophysiological tumour development by altering m6A modification and expression levels in tumour oncogenes and suppressor genes. Skin cancers are by far the most common malignancies in humans, with well over a million cases diagnosed each year. Skin cancers are grouped into two main categories: melanoma and non-melanoma skin cancers (NMSC), based on cell origin and clinical behaviour. In this review, we summarize m6A methylation functions in different skin cancers, and discuss how m6A methylation is involved in disease development and progression. Moreover, we review potential prognostic biomarkers and molecular targets for early skin cancer diagnosis and treatment.

miR-24-3p obstructs the proliferation and migration of human skin fibroblasts after thermal injury by targeting PPAR-ß and positively regulated by NF-κB.

Thermal injury repair is a complex process during which the maintenance of the proliferation and migration of human skin fibroblasts (HSFs) exert a crucial role. MicroRNAs have been proven to exert an essential function in repairing skin burns. This study delves into the regulatory effects of miR-24-3p on the migration and proliferation of HSFs that have sustained a thermal injury, thereby, providing deeper insight into thermal injury repair pathogenesis. The PPAR-ß protein expression level progressively increased in a time-dependent manner on the 12th, 24th and 48th hour following the thermal injury of the HSFs. The knockdown of PPAR-ß markedly suppressed the proliferation of and migration of HSF. Following thermal injury, the knockdown also promoted the inflammatory cytokine IL-6, TNF-α, PTGS-2 and P65 expression. PPAR-ß contrastingly exhibited an opposite trend. A targeted relationship between PPAR-ß and miR-24-3p was predicted and verified. miR-24-3p inhibited thermal injured HSF proliferation and migration and facilitated inflammatory cytokine expression through the regulation of PPAR-ß. p65 directly targeted the transcriptional precursor of miR-24 and promoted miR-24 expression. A negative correlation between miR-24-3p expression level and PPAR-ß expression level in rats' burnt dermal tissues was observed. Our findings reveal that miR-24-3p is conducive to rehabilitating the denatured dermis, which may be beneficial in providing effective therapy of skin burns.

Nucleolin regulates the proliferation of vascular smooth muscle cells in atherosclerotic via Aurora B.

Vascular smooth muscle cells (VSMCs) play a significant role in atherosclerosis. As a multifunctional protein, nucleolin (NCL) is involved in many important physiological and pathological processes. In this study, we aimed to investigate the role of nucleolin in VSMCs proliferation and cell cycle. The expression of nucleolin increased in VSMCs of mice with aortas advanced plaques. With the left common carotid-artery ligation-injury model, immunofluorescence staining revealed that nucleolin and Ki67 expression increased in VSMCs in mice left carotid artery compared with right carotid artery after surgery. POVPC or ox-LDL up-regulated nucleolin mRNA and protein expression in a dose- and time-dependent manner in HAVSMCs. POVPC (5µg/ml) or ox-LDL (50µg/ml) promoted the proliferation of HAVSMCs. Nucleolin ablation relieved the pro-proliferation role of VSMCs. The cell cycle assay and cell ability results showing that POVPC or ox-LDL increased the proliferation, but nucleolin ablation inhibited the proliferation of HAVSMCs. And nucleolin ablation can prevent DNA replication at S phase and induce cell cycle arrest in S phase. The bioinformatics database predicts protein-protein interactions with nucleolin and aurora B. Nucleolin overexpression and ablation affected the expression of aurora B. These findings indicate for the first time that nucleolin actively involved the proliferation of VSMCs via aurora B.

LncRNA H19 is involved in myocardial ischemic preconditioning via increasing the stability of nucleolin protein.

Myocardial ischemic preconditioning (IP) is defined as a brief period of myocardial ischemia/reperfusion (I/R) that significantly reduces injury during the subsequent exposure to long-term I/R. However, the underlying mechanisms of myocardial IP are yet to be elucidated. This study investigated the expression and roles of long noncoding RNA (lncRNA) H19 in myocardial IP in vitro and in vivo. LncRNA H19 expression levels were analyzed by quantitative reverse-transcription polymerase chain reaction, cell viability was determined by the Cell Counting Kit-8 assay, apoptosis was evaluated based on the caspase 3 activity, and RNA immunoprecipitation was performed to examine the interaction between lncRNA H19 and nucleolin. The results of this study showed that lncRNA H19 expression was significantly upregulated in mouse hearts subjected to myocardial IP, in rat H9C2 cells exposed to H2 O2 preconditioning (H2 O2 -PC), and in neonatal rat cardiomyocytes subjected to hypoxia preconditioning. H19 knockdown abrogated the H2 O2 -PC-mediated protection in cardiomyocytes evidenced by the decreased cell viability and increased caspase-3 activity. Conversely, H19 overexpression enhanced the protective role of H2 O2 -PC in cardiomyocytes. In addition, H19 overexpression increased the expression of nucleolin, whereas H19 ablation abrogated H2 O2 -PC-induced upregulation of nucleolin in cardiomyocytes. Furthermore, H19 overexpression increased the stabilization of nucleolin; an interaction between H19 and nucleolin was identified using the RNA-protein interaction studies. Furthermore, nucleolin small interfering RNA relieved the protective role of lncRNA H19. These findings demonstrated that the lncRNA H19 is involved in myocardial IP via increasing the stability of nucleolin protein and lncRNA H19 may represent a potential therapeutic target for the treatment of the myocardial injury.

CARD9 promotes autophagy in cardiomyocytes in myocardial ischemia/reperfusion injury via interacting with Rubicon directly.

Autophagy in cardiomyocyte is involved in myocardial ischemia/reperfusion (M-I/R) injury. Caspase recruitment domain-containing protein 9 (CARD9) plays a critical role in cardiovascular diseases (CVDs) such as hypertension and cardiac fibrosis. However, its role in autophagy following M-I/R injury is yet to be fully elucidated. Here, we found that CARD9 expression increased in M-I/R mouse hearts, and in H9c2 or neonatal rat ventricular myocytes (NRVMs) in response to hypoxia/reoxygenation (H/R) or H2O2. CARD9-/- mice exhibited a significant cardiac dysfunction following M-I/R injury (30 min of left ascending coronary (LAD) ischemia and 12 h of reperfusion) compared to wild-type (WT) mice. CARD9 deletion impaired autophagy during M-I/R in vivo and in vitro, evidenced by decrease of microtubule-associated protein 1 light chain 3 (LC3) lipidation and p62 accumulation. Conversely, CARD9 overexpression increased autophagic flux as indicated by enhanced expression of LC3 II/LC3 I and a reduction in p62. The protective effect of CARD9 on cardiomyocytes against H/R-induced oxidative stress was abolished by treatment with autophagy inhibitors, 3-methyladenine (3-MA) or Bafilomycin A1(BafA1). CARD9 interacted with RUN domain Beclin-1-interacting cysteine-rich-containing (Rubicon), a negative regulator of autophagy, and enhanced UV-irradiation-resistance-associated gene (UVRAG)-Beclin1-phosphatidylinositol 3-kinase catalytic subunit type 3 (PI3KC3) interaction and UVRAG-Vps16-mediated Rab7 activation to promote autophagosome formation, maturation, and endocytosis. Ablation of Rubicon by siRNA effectively prevented the detrimental effect of CARD9 knockdown on cardiomyocytes. These results suggest that CARD9 has protective effects on the myocardium against M-I/R injury by activating autophagy and restoring autophagic flux in vivo and in vitro.

Effect of MIPU1 gene interference on biological behavior of U251 cell line. / shRNA干扰MIPU1åŸºå› å¯¹è„‘æ˜Ÿå½¢ç»†èƒžç˜¤U251细胞生物学行为的影响.

OBJECTIVES: To investigate effect of MIPU1 silence on proliferation, apoptosis, migration and invasion in U251 cells. METHODS: The shRNA recombinant plasmids targeting MIPU1 gene was transfected into U251 cells. Western blotting was used to identify the inhibitory efficiency at 72 h after transfection. The cell viability was measured by MTT colorimetric assay. Hoechest staining and caspase-3 activity were used to detect apoptosis. Then wound healing assay and transwell migration assay were applied to detect the migration and invasion of cells. RESULTS: The expression of MIPU1 protein was effectively knocked down in transfected cells (P<0.05). The cellular proliferation was obviously inhibited and apoptosis was increased in shRNA-transfected MIPU1 cells (all P<0.05). The migration and invasion ability of cells transfected with positive plasmid was lower than that in the control group (P<0.05). CONCLUSIONS: Down-regulation of MIPU1 can promote apoptosis while inhibit the proliferation, invasion, and migration of U251 cells.

Phosphorylation of nucleolin is indispensable to upregulate miR-21 and inhibit apoptosis in cardiomyocytes.

Nucleolin is a multifunctional phosphoprotein and is involved in protecting from myocardial ischemia/reperfusion (I/R) injury. The function of nucleolin is regulated by posttranslational modifications, including phosphorylation and glycosylation. To study whether phosphorylation of nucleolin (P-nucleolin) was involved in the protection from myocardial I/R injury. We investigated the expression pattern of P-nucleolin (Thr-76 and 84) in hearts subjected to I/R injury, or rat cardiac myoblast cells (H9C2) subjected to hydrogen peroxide (H 2 O 2 ). The results showed that the expression of P-nucleolin and the ratio of P-nucleolin/nucleolin were significantly increased both in vivo and in vitro. Mutant nucleolin was obtained by site directed mutagenesis in vitro: threonine at 76 and 84 was replaced by alanine, and we found that the protective effect of nucleolin on apoptosis induced by oxidative stress was dependent on its phosphorylation at 76 and 84 in H9C2 cells. Furthermore, the cardio-protective roles of P-nucleolin (Thr-76 and 84) in H9C2 cardiomyocytes, were attributable to the upregulation of microRNA (miR)-21. Further analysis found that P-nucleolin (Thr-76 and 84) could bind to miR-21, and P-nucleolin colocalized with argonaute 2 (Ago2) in cytoplasm and could interact with Ago2 in a RNA-independent manner under cell oxidative stress. The current study revealed that P-nucleolin (Thr-76 and 84) increased in I/R injury myocardium, P-nucleolin was indispensable to upregulate miR-21 and inhibited apoptosis induced by H 2 O 2 in H9C2 cardiomyocytes. These findings provided new insight into the molecular mechanisms of nucleolin in myocardial I/R injury and oxidative stress cells.

Nucleolin protects against doxorubicin-induced cardiotoxicity via upregulating microRNA-21.

Nucleolin is a multifunctional protein and participates in many important biological processes. Our previous study found that nucleolin protects the heart against myocardial ischemia-reperfusion injury. In this study, we aimed to investigate the role of nucleolin in doxorubicin (DOX)-induced cardiotoxicity. The expression pattern of nucleolin in hearts subjected to DOX injury was investigated, and we found that administration of DOX induced nucleolin expression significantly in vivo and in vitro. Gene transfection and RNA interference approaches were used in cardiomyocytes to investigate the function of nucleolin. Nucleolin overexpression protects cardiomyocytes against DOX-induced injury. Nucleolin-ablated cardiomyocytes become susceptible to the injury induced by DOX. The hearts of cardiac-myocyte-specific nucleolin transgenic mice are more resistant to DOX injury. Furthermore, nucleolin upregulates microRNA(miRNA)-21 expression in vivo and in vitro, and the miRNA-21 inhibitor negates the protective effect of nucleolin against injury induced by DOX. These results have demonstrated that nucleolin is involved in the regulation of DOX-induced cardiac injury and dysfunction via the regulation of miRNA-21 expression, and may be a novel therapeutic target for DOX-induced cardiotoxicity.

Nucleolin protects macrophages from oxLDL-induced foam cell formation through up-regulating ABCA1 expression.

Our recent studies have indicated that nucleolin, as a multifunctional RNA-binding protein, exerts protective effects in the myocardial cells and endothelial cells under the condition of oxidative stress. However, the function of nucleolin and its potential mechanism in macrophage-derived foam cell formation remain largely unexplored. ApoE-/- mice were fed with a high-fat diet (HFD) for 10-24 weeks. Protein expression was measured by western blotting or immunofluorescence, and gene expression at the mRNA level was detected by qRT-PCR. The level of lipid in macrophages was examined by Oil Red O staining, high-performance liquid chromatography (HPLC) and NBD-cholesterol. Actinomycin D (Act D) was used to determine the stability of ABCA1 mRNA in macrophages. The interaction of nucleolin with ABCA1 mRNA was assessed using co-immunoprecipitation (co-IP). The aortas advanced plaques demonstrated significantly lower levels of nucleolin protein compared with early plaques in ApoE-/- mice, in which the macrophage foam cells occupied main body. Nucleolin expression at the mRNA and protein levels in RAW264.7 macrophages was significantly reduced by oxidized low-density lipoprotein (oxLDL) in a dose- and time-dependent manner. Furthermore, nucleolin overexpression markedly attenuated lipid accumulation in oxLDL-challenged macrophages through increasing cholesterol efflux. In addition, nucleolin overexpression significantly increased the expression of ATP-binding cassette transporter A1 (ABCA1) at the mRNA and protein levels without affecting expressions of scavenger receptors (SR)-A, SR-B1, CD36 and ATP-binding cassette transporter G1 (ABCG1) at the mRNA level. Moreover, nucleolin overexpression increased the stability of ABCA1 mRNA in macrophages, whereas nucleolin ablation abrogated the oxLDL-induced up-regulation of ABCA1. The up-regulation of ABCA1 by nucleolin resulted from its protein-RNA interaction. Our data suggested that nucleolin inhibited foam cell formation through enhancing stability of ABCA1 mRNA and subsequently increasing cholesterol efflux.

[Effect of nucleolin on cardiac cell apoptosis in Type 2 diabetic cardiomyopathy mice].

OBJECTIVE: To investigate the effect of nucleolin on cardiac cell apoptosis in Type 2 diabetic cardiomyopathy mice.
 Methods: Mice were fed with high-fat and high-sugar food for 20 weeks (mice were injected intraperitoneally with 60 mg/kg streptozotocin in the 5th and 6th weeks) to establish a mouse model of Type 2 diabetes. The mice were divided into 4 groups: a wild type (WT) control group, a nucleolin transgenic (TG) control group, a WT diabetic group, a TG diabetic group. Diabetes-related indicators were detected at the end of the 8th week. At the end of the 20th week, HE staining was used to observe myocardial morphological changes; TUNEL staining and caspase-3 activity were used to detect the extent of apoptosis of cardiac myocytes.
 Results: The level of fasting blood glucose was significantly increased in the diabetic group than that in the control group. In WT diabetic group, myocardial disarrangement, fragmentation and dissolution were observed (determined by HE staining); cellular apoptosis (determined by TUNEL staining and caspase-3 activity) also increased markedly in the WT diabetic group. Compared with the wild mice in the diabetic group, myocardial morphological changes and cardiac myocytes apoptosis were alleviated significantly. 
 Conclusion: Nucleolin overexpression affectes the occurrence and development of diabetic cardiomyopathy through inhibition of cardiac myocyte apoptosis.

Nucleolin enhances the proliferation and migration of heat-denatured human dermal fibroblasts.

Denatured dermis, a part of dermis in burned skin, has the ability to restore its normal morphology and functions after their surrounding microenvironment is improved. However, the cellular and molecular mechanisms by which the denatured dermis could improve wound healing are still unclear. This study aimed to investigate the role of nucleolin during the recovery of heat-denatured human dermal fibroblasts. Nucleolin mRNA and protein expression were significantly increased time-dependently during the recovery of heat-denatured human dermal fibroblasts (52 °C, 30 seconds). Heat-denaturation promoted a time-dependent cell proliferation, migration, chemotaxis, and scratched wound healing during the recovery of human dermal fibroblasts. These effects were prevented by knockdown of nucleolin expression with small interference RNA (siRNA), whereas overexpression of nucleolin enhanced cell proliferation, migration, and chemotaxis of human dermal fibroblasts with heat-denaturation. In addition, the expression of transforming growth factor-beta 1(TGF-ß1) was significantly increased during the recovery of heat-denatured dermis and human dermal fibroblasts. TGF-ß1 expression was up-regulated by nucleolin in human dermal fibroblasts. The results suggest that nucleolin expression is up-regulated, and play an important role in promoting cell proliferation, migration, and chemotaxis of human dermal fibroblasts during the recovery of heat-denatured dermis with a mechanism probably related to TGF-ß1.

MiR-21 Protected Cardiomyocytes against Doxorubicin-Induced Apoptosis by Targeting BTG2.

Doxorubicin (DOX) is an anthracycline drug with a wide spectrum of antineoplastic activities. However, it causes cardiac cytotoxicity, and this limits its clinical applications. MicroRNA-21 (miR-21) plays a vital role in regulating cell proliferation and apoptosis. While miR-21 is preferentially expressed in adult cardiomyocytes and involved in cardiac development and heart disease, little is known regarding its biological functions in responding to DOX-induced cardiac cytotoxicity. In this study, the effects of DOX on mouse cardiac function and the expression of miR-21 were examined in both mouse heart tissues and rat H9C2 cardiomyocytes. The results showed that the cardiac functions were more aggravated in chronic DOX injury mice compared with acute DOX-injury mice; DOX treatment significantly increased miR-21 expression in both mouse heart tissue and H9C2 cells. Over-expression of miR-21 attenuated DOX-induced apoptosis in cardiamyocytes whereas knocking down its expression increased DOX-induced apoptosis. These gain- and loss- of function experiments showed that B cell translocation gene 2 (BTG2) was a target of miR-21. The expression of BTG2 was significantly decreased both in myocardium and H9C2 cells treated with DOX. The present study has revealed that miR-21 protects mouse myocardium and H9C2 cells against DOX-induced cardiotoxicity probably by targeting BTG2.

The expression and proangiogenic effect of nucleolin during the recovery of heat-denatured HUVECs.

BACKGROUND: The present study aims to examine the expression patterns and roles of nucleolin during the recovery of heat-denatured human umbilical vein endothelial cells (HUVECs). METHODS: Deep partial thickness burn model in Sprague-Dawley rats and the heat denatured cell model (52°C, 35s) were used. The expression of nucleolin was measured using Western blot analysis and real-time PCR. Angiogenesis was assessed using in vitro parameters including endothelial cell proliferation, transwell migration assay, and scratched wound healing. Gene transfection and RNA interference approaches were employed to investigate the roles of nucleolin. RESULTS: Nucleolin mRNA and protein expression showed a time-dependent increase during the recovery of heat-denatured dermis and HUVECs. Heat-denaturation time-dependently promoted cell growth, adhesion, migration, scratched wound healing and formation of tube-like structures in HUVECs. These effects of heat denaturation on endothelial wound healing and formation of tube-like structures were prevented by knockdown of nucleolin, whereas over-expression of nucleolin increased cell growth, migration, and formation of tube-like structures in cultured HUVEC endothelial cells. In addition, we found that the expression of vascular endothelial growth factor (VEGF) increased during the recovery of heat-denatured dermis and HUVECs, and nucleolin up-regulated VEGF in HUVECs. CONCLUSIONS: The present study reveals that the expression of nucleolin is up-regulated, and plays a pro-angiogenic role during the recovery of heat-denatured dermis and its mechanism is probably dependent on production of VEGF. GENERAL SIGNIFICANCE: We find a novel and important pro-angiogenic role of nucleolin during the recovery of heat-denatured dermis.

[Expression of nucleolin in pressure overload-induced cardiac hypertrophy rats].

OBJECTIVE: To detect the expression of nucleolin in cardiac hypertrophy rats induced by pressure overload. METHODS: A total of 40 SD rats with body weight 180 g and 220 g were recruited and randomly divided into 2 groups: a transverse aortic constriction (TAC) group and a sham surgery group. Cardiac hypertrophy model was employed by transverse aortic constriction surgery. Then 2 weeks and 4 weeks after the experiment, the heart mass index (HMI), left ventricle mass index (LVMI) were measured. ß-MHC mRNA in the heart tissue was detected with RT-PCR. Nucleolin in the heart, brain and kidney was respectively detected with Western blot. RESULTS: Compared with the sham surgery group, HMI, LVMI in the TAC group increased significantly (P<0.01) 4 weeks after the surgery; the expression of ß-MHC mRNA in the heart tissue increased (P<0.05) in the TAC group 4 weeks after the surgery; and the expression of nucleolin protein in the heart tissue of the TAC group was remarkably upregulated (P<0.05) 2 weeks after the surgery, with no change in the brain and kidney tissue between the 2 groups. CONCLUSION: Expression of nucleolin protein has been upregulated in response to pressure overload, which may suggest that nucleolin plays a role in cardiac hypertrophy induced by pressure overload.

[Nucleolus expression in diabetic cardiomyopathy].

OBJECTIVE: To investigate the nucleolus expression in the diabetic cardiomyopathy. METHODS: The rats were divided into a control group and a type II diabetic cardiomyopathy group (model group). In the model group, rats were fed with high-fat and high-sugar food (rats were intravenously injected with 60 mg/kg chain urea with cephalosporins in the 5th and 6th weeks in mice). The level of blood glucose was determined at the end of 8th week and the level of fasting blood glucose was examined at the end of 20th week. The ratio of the heart mass and body mass was calculated, and the pathological changes in myocardial morphology were observed. The immunohistochemical method and Western blot were used to detect the expression level of myocardial nucleolin. RESULTS: The level of fasting blood glucose was significantly increased in the diabetic model group than that in the control group (P<0.05). Rats in the model group were found hypertrophic cardic cells, with fracture, dissolusion, and disordered arrangement. Immunohistochemical staining and Western blot showed the protein levels of myocardial nucleolin in the model group were obviously higher than those in the control group (P<0.05). CONCLUSION: Nucleolin may play a role in the pathogenesis and development of the diabetic cardiomyopathy.

The liquid-liquid phase separation in programmed cell death.

In recent years, the physical phenomenon of liquid-liquid phase separation has been widely introduced into biological research. Membrane-free organelles have been found to exist in cells that were driven by liquid-liquid phase separation. Intermolecular multivalent interactions can drive liquid-liquid phase separation to form condensates that are independent of other substances in the environment and thus can play an effective role in regulating multiple biological processes in the cell. The way of cell death has also long been a focus in multiple research. In the face of various stresses, cell death-related mechanisms are crucial for maintaining cellular homeostasis and regulating cell fate. With the in-depth study of cell death pathways, it has been found that the process of cell death was also accompanied by the regulation of liquid-liquid phase separation and played a key role. Therefore, this review summarized the roles of liquid-liquid phase separation in various cell death pathways, and explored the regulation of cell fate by liquid-liquid phase separation, with the expectation that the exploration of the mechanism of liquid-liquid phase separation would provide new insights into the treatment of diseases caused by regulated cell death.

Nucleolin myocardial-specific knockout exacerbates glucose metabolism disorder in endotoxemia-induced myocardial injury.

Background: Sepsis-induced myocardial injury, as one of the important complications of sepsis, can significantly increase the mortality of septic patients. Our previous study found that nucleolin affected mitochondrial function in energy synthesis and had a protective effect on septic cardiomyopathy in mice. During sepsis, glucose metabolism disorders aggravated myocardial injury and had a negative effect on septic patients. Objectives: We investigated whether nucleolin could regulate glucose metabolism during endotoxemia-induced myocardial injury. Methods: The study tested whether the nucleolin cardiac-specific knockout in the mice could affect glucose metabolism through untargeted metabolomics, and the results of metabolomics were verified experimentally in H9C2 cells. The ATP content, lactate production, and oxygen consumption rate (OCR) were evaluated. Results: The metabolomics results suggested that glycolytic products were increased in endotoxemia-induced myocardial injury, and that nucleolin myocardial-specific knockout altered oxidative phosphorylation-related pathways. The experiment data showed that TNF-α combined with LPS stimulation could increase the lactate content and the OCR values by about 25%, and decrease the ATP content by about 25%. However, interference with nucleolin expression could further decrease ATP content and OCR values by about 10-20% and partially increase the lactate level in the presence of TNF-α and LPS. However, nucleolin overexpression had the opposite protective effect, which partially reversed the decrease in ATP content and the increase in lactate level. Conclusion: Down-regulation of nucleolin can exacerbate glucose metabolism disorders in endotoxemia-induced myocardial injury. Improving glucose metabolism by regulating nucleolin was expected to provide new therapeutic ideas for patients with septic cardiomyopathy.

Energy Metabolism: From Physiological Changes to Targets in Sepsis-induced Cardiomyopathy.

Sepsis is a systemic inflammatory response syndrome caused by a variety of dysregulated responses to host infection with life-threatening multi-organ dysfunction. Among the injuries or dysfunctions involved in the course of sepsis, cardiac injury and dysfunction often occur and are associated with the pathogenesis of hemodynamic disturbances, also defined as sepsis-induced cardiomyopathy (SIC). The process of myocardial metabolism is tightly regulated and adapts to various cardiac output demands. The heart is a metabolically flexible organ capable of utilizing all classes of energy substrates, including carbohydrates, lipids, amino acids, and ketone bodies to produce ATP. The demand of cardiac cells for energy metabolism changes substantially in septic cardiomyopathy with distinct etiological causes and different times. This review describes changes in cardiomyocyte energy metabolism under normal physiological conditions and some features of myocardial energy metabolism in septic cardiomyopathy, and briefly outlines the role of the mitochondria as a center of energy metabolism in the septic myocardium, revealing that changes in energy metabolism can serve as a potential future therapy for infectious cardiomyopathy.

New progress with calcium-binding protein S100A16 in digestive system disease.

INTRODUCTION: This review summarizes and analyzes the abnormal expression and mechanism of S100A16 in digestive system diseases, which is expected to provide new ideas and methods for adjuvant treatment and prognosis evaluation of digestive system diseases. AREAS COVERED: Based on original publications found in database systems (PubMed, Cochrane), we introduce the mechanism and research progress of S100A16 in digestive system tumors, inflammatory bowel disease and fatty liver. EXPERT OPINION: S100A16 is closely related to the proliferation, migration, and invasion of digestive system tumor cells. Further, it plays an important role in inflammatory bowel disease and fatty liver.