Autophagy-Related LC3 Accumulation Interacted Directly With LIR Containing RIPK1 and RIPK3, Stimulating Necroptosis in Hypoxic Cardiomyocytes.

The exact relationships and detailed mechanisms between autophagy and necroptosis remain obscure. Here, we demonstrated the link between accumulated autophagosome and necroptosis by intervening with autophagic flux. We first confirmed that the LC3 interacting region (LIR) domain is present in the protein sequences of RIPK1 and RIPK3.

The Lysosomal Membrane Protein Lamp2 Alleviates Lysosomal Cell Death by Promoting Autophagic Flux in Ischemic Cardiomyocytes.

Lysosomal membrane permeabilization (LMP) has recently been recognized as an important cell death pathway in various cell types. However, studies regarding the correlation between LMP and cardiomyocyte death are scarce. Lysosomal membrane-associated protein 2 (Lamp2) is an important component of lysosomal membranes and is involved in both autophagy and LMP.

Tumor necrosis factor receptor-associated protein 1 regulates hypoxia-induced apoptosis through a mitochondria-dependent pathway mediated by cytochrome c oxidase subunit II.

Background: Tumor necrosis factor receptor-associated protein 1 (TRAP1) plays a protective effect in hypoxic cardiomyocytes, but the precise mechanisms are not well clarified. The study is aimed to identify the mechanism of TRAP1 on hypoxic damage in cardiomyocytes.

Methods: In this study, the effects of TRAP1 and cytochrome c oxidase subunit II (COXII) on apoptosis in hypoxia-induced cardiomyocytes were explored using overexpression and knockdown methods separately.

PI3K-AKT Pathway Protects Cardiomyocytes Against Hypoxia-Induced Apoptosis by MitoKATP-Mediated Mitochondrial Translocation of pAKT.

Background/aims: The phosphatidylinositol-3-kinase -AKT (PI3K-AKT) is an important intracellular signal pathway in regulating cell proliferation, differentiation and apoptosis. In previous studies, we've demonstrated that PI3K-AKT pathway protects cardiomyocytes from ischemic and hypoxic apoptosis through mitochondrial function. However, the molecular mechanisms underlying hypoxia-induced cardiomyocyte apoptosis via PI3K-AKT pathway remain ill-defined.

Effects of Preoperative Isokinetic Eccentric Training and Whey Protein Isolate Supplement on Quadriceps Strength and Knee Function in Patients with Anterior Cruciate Ligament Rupture.

Objective To explore the effect of preoperative isokinetic eccentric training with or not whey protein isolate supplement before operation on lower limb muscle strength and knee function in patients with anterior cruciate ligament (ACL) rupture. Methods A total of 22 male volunteers aged 18-40 years with ACL rupture were recruited in outpatient service. With randomized block design,subjects were randomly assigned to isokinetic eccentric training (IE) group and isokinetic eccentric training with whey protein isolate supplement (IE+WPI) group.

MicroRNA-335-5p suppresses lower extremity deep venous thrombosis by targeted inhibition of PAI-1 via the TLR4 signalingpathway.

This study aims to investigate the effects of microRNA-335-5p (miR-335-5p) on lower-extremity deep vein thrombosis (LEDVT) by targeting PAI-1 through the TLR4 signaling pathway in rat models. siRNA, mimic, and inhibitor were used for transfection. The miR-335-5p expression was detected by in situ hybridization.

Tumor necrosis factor receptor-associated protein 1 improves hypoxia-impaired energy production in cardiomyocytes through increasing activity of cytochrome c oxidase subunit II.

Tumor necrosis factor receptor-associated protein 1 protects cardiomyocytes against hypoxia, but the underlying mechanisms are not completely understood. In the present study, we used gain- and loss-of-function approaches to explore the effects of tumor necrosis factor receptor-associated protein 1 and cytochrome c oxidase subunit II on energy production in hypoxic cardiomyocytes. Hypoxia repressed ATP production in cultured cardiomyocytes, whereas overexpression of tumor necrosis factor receptor-associated protein 1 significantly improved ATP production.

The potential regulatory roles of NAD(+) and its metabolism in autophagy.

(Macro)autophagy mediates the bulk degradation of defective organelles, long-lived proteins and protein aggregates in lysosomes and plays a critical role in cellular and tissue homeostasis. Defective autophagy processes have been found to contribute to a variety of metabolic diseases. However, the regulatory mechanisms of autophagy are not fully understood.

HSP27 phosphorylation protects against endothelial barrier dysfunction under burn serum challenge.

F-actin rearrangement is an early event in burn-induced endothelial barrier dysfunction. HSP27, a target of p38 MAPK/MK2 pathway, plays an important role in actin dynamics through phosphorylation. The question of whether HSP27 participates in burn-related endothelial barrier dysfunction has not been identified yet.

Infection-stimulated anemia results primarily from interferon gamma-dependent, signal transducer and activator of transcription 1-independent red cell loss.

Background: Although the onset of anemia during infectious disease is commonly correlated with production of inflammatory cytokines, the mechanisms by which cytokines induce anemia are poorly defined. This study focused on the mechanism research.

Methods: Different types of mice were infected perorally with Toxoplasma gondii strain ME49.

[Protein and mRNA expression of CTGF, CYR61, VEGF-C and VEGFR-2 in bone marrow of leukemia patients and its correlation with clinical features].

This study was aimed to investigate the mRNA and protein expression of CTGF, CYR61, VEGF-C and VEGFR-2 in bone marrow of patients with leukemia, and to analyze the role and clinical significance of these 4 factors in genesis and development of leukemia, infiltration and metastasis of leukemic cells. A total of 100 cases of newly diagnosed leukemia, 26 cases of acute leukemia in complete remission and 30 controls were enrolled in this study. The mononuclear cells of bone marrow were collected, the mRNA and protein expression levels of CTGF, CYR61, VEGF-C, VEGFR-2 in leukemia patients and controls were detected by real time PCR and Western blot, respectively.

Identification of differentially expressed serum proteins in infectious purpura fulminans.

Purpura fulminans (PF) is a life-threatening hemorrhagic condition. Because of the rarity and randomness of the disease, no improvement in treatment has been made for a long time. In this study, we assessed the serum proteome response to PF by comparing serum proteins between healthy controls and PF patient.

Phosphorylation of DYNLT1 at serine 82 regulates microtubule stability and mitochondrial permeabilization in hypoxia.

Hypoxia-induced microtubule disruption and mitochondrial permeability transition (mPT) are crucial events leading to fatal cell damage and recent studies showed that microtubules (MTs) are involved in the modulation of mitochondrial function. Dynein light chain Tctex-type 1 (DYNLT1) is thought to be associated with MTs and mitochondria. Previously we demonstrated that DYNLT1 knockdown aggravates hypoxia-induced mitochondrial permeabilization, which indicates a role of DYNLT1 in hypoxic cytoprotection.

Downregulation of CD9 in keratinocyte contributes to cell migration via upregulation of matrix metalloproteinase-9.

Tetraspanin CD9 has been implicated in various cellular and physiological processes, including cell migration. In our previous study, we found that wound repair is delayed in CD9-null mice, suggesting that CD9 is critical for cutaneous wound healing. However, many cell types, including immune cells, endothelial cells, keratinocytes and fibroblasts undergo marked changes in gene expression and phenotype, leading to cell proliferation, migration and differentiation during wound repair, whether CD9 regulates kerationcytes migration directly remains unclear.

Protective effects of enalapril, an angiotensin-converting enzyme inhibitor, on multiple organ damage following scald injury in rats.

The aim of this study is to investigate the effects of enalapril, an angiotensin-converting enzyme inhibitor, on multiple organ damage after scald injury. Healthy adult rats (half male and half female; 8-12 weeks old) were randomly assigned to the following treatments: sham operation, scald injury, and intraperitoneal enalapril (1, 2, and 4 mg/kg body weight) treatment after scalding. At 1, 12, and 24 H postscald, left ventricular and aortic hemodynamics were measured using a multichannel physiological recorder.

Defining the complex behavior of the heart.

Previous studies on heart growth and development have elucidated important gene- and cellular-level changes. The development of improved biochemical, mathematical, and computational methods has enabled more accurate elaboration of the structural and functional processes of the heart. Systematic analyses of heart complexity have revealed the differences between normal and pathological growth and development in terms of self-organizational ability, energy balance, clock regulation, and heart rate variability.

Identification of mitochondria translation elongation factor Tu as a contributor to oxidative damage of postburn myocardium.

Mitochondrial damage plays an important role in mediating postburn cardiac injury. To elucidate the pivotal mitochondrial proteins and pathways underlying postburn cardiac injury, mitochondria were purified from control and postburn rat hearts. 2-dimensional gel electrophoresis (2-DE) and HPLC-chip-MS/MS analyses revealed 9 differentially expressed proteins, 3 of which were further validated by Western blotting.

Nicotinamide pretreatment protects cardiomyocytes against hypoxia-induced cell death by improving mitochondrial stress.

Background/aims: Nicotinamide plays a protective role in hypoxia-induced cardiomyocyte dysfunction. However, the underlying molecular mechanisms remain poorly understood. The purpose of this study was to investigate these and the effect of nicotinamide pretreatment on hypoxic cardiomyocytes.

Microtubular stability affects pVHL-mediated regulation of HIF-1alpha via the p38/MAPK pathway in hypoxic cardiomyocytes.

Background: Our previous research found that structural changes of the microtubule network influence glycolysis in cardiomyocytes by regulating the hypoxia-inducible factor (HIF)-1α during the early stages of hypoxia. However, little is known about the underlying regulatory mechanism of the changes of HIF-1α caused by microtubule network alternation. The von Hippel-Lindau tumor suppressor protein (pVHL), as a ubiquitin ligase, is best understood as a negative regulator of HIF-1α.

[Expression of CYR61, CTGF, VEGF-C, VEGFR-2 mRNA in bone marrow of leukemia patients and its clinical significance].

The study was aimed to detect the levels of CYR61, CTGF, VEGF-C, VEGFR-2 mRNA in bone marrow (BM) of leukemia patients and investigate the interaction of CYR61, CTGF, VEGF-C, VEGFR-2 proteins in occurrence, development, infiltration and metastasis of leukemia and its clinical significance, to find a new tumor marker for diagnosis and treatment of leukemia with some new directions. 74 patients with leukemia were enrolled in this study, 38 out of them were males and 36 were females, aged from 6 to 77 years old with the median age of 45 years old. In the control group, 7 males and 5 females, aged from 16 to 78 years old with the median age of 46.

MAP4 mechanism that stabilizes mitochondrial permeability transition in hypoxia: microtubule enhancement and DYNLT1 interaction with VDAC1.

Mitochondrial membrane permeability has received considerable attention recently because of its key role in apoptosis and necrosis induced by physiological events such as hypoxia. The manner in which mitochondria interact with other molecules to regulate mitochondrial permeability and cell destiny remains elusive. Previously we verified that hypoxia-induced phosphorylation of microtubule-associated protein 4 (MAP4) could lead to microtubules (MTs) disruption.

Activation of the prolyl-hydroxylase oxygen-sensing signal cascade leads to AMPK activation in cardiomyocytes.

The proline hydroxylase domain-containing enzymes (PHD) act as cellular oxygen sensors and initiate a hypoxic signal cascade to induce a range of cellular responses to hypoxia especially in the aspect of energy and metabolic homeostasis regulation. AMP-activated protein kinase (AMPK) is recognized as a major energetic sensor and regulator of cardiac metabolism. However, the effect of PHD signal on AMPK has never been studied before.

Expression of the stem cell marker, Nanog, in human endometrial adenocarcinoma.

The embryonic stem cell self-renewal gene, Nanog, has been shown to be expressed in several tumor types and to regulate tumor development. The aim of this study was to carry out a detailed analysis of Nanog expression in human endometrial adenocarcinoma (EAC). Immunohistochemical analysis and reverse transcription-polymerase chain reaction were used to characterize Nanog, Sox2, and Oct4 expression in tissue arrays containing EAC, benign endometrium samples, and tumorosphere cells.

Adenosine A1 receptor activation reduces opening of mitochondrial permeability transition pores in hypoxic cardiomyocytes.

1. Adenosine A(1) receptors (A(1)R) play an important role in cardioprotection against hypoxic damage and the opening of mitochondrial permeability transition pores (MPTP) is central to the regulation of cell apoptosis and necrosis. However, it is still unclear whether A(1)R open MPTP in hypoxic cardiomyocytes.

[Expression of cyclooxygenase-2 in bone marrow cells of leukemia patients and its association with angiogenesis].

The objective of this study was to investigate the effect of cyclooxygenase-2 (COX-2) in the angiogenesis of bone marrow in leukemia patients. 51 patients with newly diagnosed acute leukemia were taken as study objects, 18 healthy volunteers were enrolled in the control group. Bone marrow microvessel density (MVD) in bone marrow biopsy tissue section was determined with immunohistochemistry method, the vascular endothelial growth factor level in serum was detected with ELISA method and the expression of cyclooxygenase-2 in bone marrow cells was assayed by flow cytometry.