Yu Zhu

Bio: Yu Zhu is an academic researcher from Third Military Medical University. The author has contributed to research in topics: Shock (circulatory) & Sepsis. The author has an hindex of 16, co-authored 47 publications receiving 640 citations.

Ideal permissive hypotension to resuscitate uncontrolled hemorrhagic shock and the tolerance time in rats.

Abstract: Background Studies have shown that permissive hypotension for uncontrolled hemorrhagic shock can result in good resuscitation outcome. The ideal target mean arterial pressure (MAP) and the tolerance time for permissive hypotension have not been determined. Methods To elucidate the ideal target MAP and tolerance time for permissive hypotension with uncontrolled hemorrhagic shock rats, the effects of different target MAPs (40, 50, 60, 70, 80, and 100 mmHg) and 60-, 90-, and 120-min permissive hypotension (50 mmHg) on uncontrolled hemorrhagic shock were observed. Results Rats in normotensive groups (80 and 100 mmHg) had increased blood loss (101%, 126% of total blood volume), decreased hematocrit, decreased vital organ (liver and kidney) and mitochondrial function, and decreased animal survival rate (1 of 10). Rats in the 50- and 60-mmHg target MAP groups had decreased blood loss (52% and 69%, respectively), good hematocrit and vital organ and mitochondrial function, stable hemodynamics, and increased animal survival (8 of 10 and 6 of 10, respectively). Rats in the 40-mmHg target MAP group, although having decreased blood loss (39%), appeared to have very inferior organ function and animal survival (2 of 10). Animal survival (1 of 10) and vital organ function in the 120-min permissive hypotension group were significantly inferior to the 60- and 90-min groups. The 60- and 90-min groups had similar animal survival (8 of 10 and 6 of 10) and vital organ function. Conclusion A target resuscitation pressure of 50-60 mmHg is the ideal blood pressure for uncontrolled hemorrhagic shock. Ninety minutes of permissive hypotension is the tolerance limit; 120 min of hypotensive resuscitation can cause severe organ damage and should be avoided.

Diabetes and hyperlipidemia induce dysfunction of VSMCs: contribution of the metabolic inflammation/miRNA pathway.

Abstract: Vascular endothelial cell injury is considered to be the major factor inducing vascular complications in metabolic diseases and plays an important role in other organ damage. With diabetic and hyperlipidemic rats and cultured VSMCs, the present study was aimed at investigating whether the early damage of VSMCs during metabolic diseases plays a critical role in vascular dysfunction and the underlying mechanisms and would be a promising treatment target. With diabetic and hyperlipidemic rats and cultured VSMCs, the changes and relationships of vascular relaxation and contractile function to the vital organ damage and the underlying mechanisms were investigated; meanwhile, the protective and preventive effects of lowering blood lipid and glucose and inhibition of diabetes and hyperlipidemia-induced vascular hyperreactivity were observed. Diabetic and hyperlipidemic rats presented hyperreactivity in vascular contractile response in the early stages. Hyperglycemia and hyperlipidemia directly affected the contractile function of VSMCs. Early application of fasudil, a specific antagonist of Rho kinase, significantly alleviated diabetes and hyperlipidemia-induced organ damage by inhibiting vascular hyperreactivity. Diabetes and hyperlipidemia-induced inflammatory response could upregulate the expression of connexins and Rho kinase by selective downregulation of the expression of miR-10a, miR-139b, miR-206, and miR-222. These findings suggest that hyperglucose and lipid may directly impair VSMCs and induce vascular hyperreactivity in the early stages. Metabolic inflammation-induced changes in the miRNA-connexin/Rho kinase regulatory pathway are the main mechanism for vascular hyperreactivity and organ damage. Measures inhibiting vascular hyperreactivity are promising for the prevention of organ damage induced by metabolic diseases.

Role of connexin 43 in vascular hyperpermeability and relationship to Rock1-MLC20 pathway in septic rats

Abstract: Connexin (Cx)43 has been shown to participate in several cardiovascular diseases. Increased vascular permeability is a common and severe complication in sepsis or septic shock. Whether or not Cx43 ...

4-Phenylbutyric Acid Reveals Good Beneficial Effects on Vital Organ Function via Anti-Endoplasmic Reticulum Stress in Septic Rats.

Abstract: Objectives:Sepsis and septic shock are the common complications in ICUs. Vital organ function disorder contributes a critical role in high mortality after severe sepsis or septic shock, in which endoplasmic reticulum stress plays an important role. Whether anti–endoplasmic reticulum stress with 4-ph

Effects of the balance in activity of RhoA and Rac1 on the shock-induced biphasic change of vascular reactivity in rats.

Abstract: Objective To investigate the effects of the balance in activity of RhoA and Rac1 on the shock-induced biphasic change in vascular reactivity and the related mechanism. Background Vascular reactivity after hemorrhagic shock shows a biphasic change. RhoA and Rac1 are the main members of a family of Rho GTPases; whether and how they participate in the regulation of the biphasic change in vascular reactivity after shock is not known. Methods The relationship of the balance of the activity RhoA and Rac1 with the changes in vascular reactivity after hemorrhagic shock, the effects of artificially changing the balance of RhoA and Rac1 activity on vascular reactivity, and the roles of Rho kinase and p21-activated kinase (PAK) in RhoA/Rac1 regulation of vascular reactivity were observed in isolated superior mesenteric arteries (SMAs) from hemorrhagic shocked rats and hypoxia-treated vascular smooth muscle cells (VSMCs). Results The reactivity of SMAs and VSMCs to norepinephrine after shock or hypoxia was positively correlated with changes in the RhoA and Rac1 activity ratio. Artificially changing the balance in activity of RhoA and Rac1 significantly changed the shock-induced biphasic response of vascular reactivity. Specific antagonist of Rho kinase and PAK (Y-27632 and PAK-18) respectively abolished the effect of activation of RhoA and Rac1. Activation of RhoA significantly increased the activity of Rho kinase and inhibited the activity of Rac1 in SMAs. Rac1 activation significantly increased the activity of PAK and decreased the activity of RhoA. Conclusions The balance in the activity of RhoA and Rac1 participated in the biphasic vascular reactivity seen after hemorrhagic shock. RhoA and Rac1 regulation of the vascular reactivity after shock are closely related to Rho kinase and the PAK pathway. RhoA regulates vascular reactivity mainly through activation of Rho kinase and inhibition of Rac1. Rac1 regulates vascular reactivity mainly through inhibition of RhoA and activation of PAK. These findings have potential significance for the treatment of vascular hyporesponsiveness.

The protective role of estrogen and estrogen receptors in cardiovascular disease and the controversial use of estrogen therapy.

Abstract: Epidemiologic studies have previously suggested that premenopausal females have reduced incidence of cardiovascular disease (CVD) when compared to age-matched males, and the incidence and severity of CVD increases postmenopause. The lower incidence of cardiovascular disease in women during reproductive age is attributed at least in part to estrogen (E2). E2 binds to the traditional E2 receptors (ERs), estrogen receptor alpha (ERα), and estrogen receptor beta (ERβ), as well as the more recently identified G-protein-coupled ER (GPR30), and can exert both genomic and non-genomic actions. This review summarizes the protective role of E2 and its receptors in the cardiovascular system and discusses its underlying mechanisms with an emphasis on oxidative stress, fibrosis, angiogenesis, and vascular function. This review also presents the sexual dimorphic role of ERs in modulating E2 action in cardiovascular disease. The controversies surrounding the clinical use of exogenous E2 as a therapeutic agent for cardiovascular disease in women due to the possible risks of thrombotic events, cancers, and arrhythmia are also discussed. Endogenous local E2 biosynthesis from the conversion of testosterone to E2 via aromatase enzyme offers a novel therapeutic paradigm. Targeting specific ERs in the cardiovascular system may result in novel and possibly safer therapeutic options for cardiovascular protection.

Ischemia/reperfusion 损害: 有免疫力的房间的角色

Abstract: Ischemia/reperfusion (I/R) injury is an inflammatory condition that is characterized by innate immunity and an adaptive immune response This review is focused on the acute inflammatory response in I/R injury, and also the adaptive immunological mechanisms in chronic ischemic disease that lead to increased vulnerability during acute events, in relation to the cell types that have been shown to mediate innate immunity to an adaptive immune response in I/R, specifically myocardial infarction Novel aspects are also highlighted in respect to the mechanisms within the cardiovascular system and cardiovascular risk factors that may be involved in the inflammatory response accompanying myocardial infarction Experimental myocardial I/R has suggested that immune cells may mediate reperfusion injury Specifically, monocytes, macrophages, T-cells, mast cells,platelets and endothelial cells are discussed with reference to the complement cascade, toll-like receptors, cytokines, oxidative stress, renin-angiotensin system, and in reference to the microvascular system in the signaling mechanisms of I/R Finally, the findings of the data summarized in this review are most important for possible translation into clinical cardiology practice and possible avenues for drug development

Plasma MicroRNA Profiling Reveals Loss of Endothelial MiR-126 and Other MicroRNAs in Type 2 Diabetes

Abstract: Rationale:MicroRNAs (miRNAs) have been implicated in the epigenetic regulation of key metabolic, inflammatory, and antiangiogenic pathways in type 2 diabetes (DM) and may contribute to common disease complications. Objective:In this study, we explore plasma miRNA profiles in patients with DM. Methods and Results:Total RNA was extracted from plasma samples of the prospective population-based Bruneck study. A total of 13 candidate miRNAs identified by microarray screening and miRNA network inference were quantified by quantitative PCR in all diabetic patients of the Bruneck study and age- and sex-matched controls (1995 evaluation, n=80 each). Quantitative PCR assessment revealed lower plasma levels of miR-20b, miR-21, miR-24, miR-15a, miR-126, miR-191, miR-197, miR-223, miR-320, and miR-486 in prevalent DM, but a modest increase of miR-28-3p. Findings emerged as robust in multivariable analysis and were independent of the standardization procedure applied. For endothelial miR-126, results were confirmed in ...

Junctional proteins of the blood-brain barrier: New insights into function and dysfunction

Abstract: The blood-brain barrier (BBB) is a highly complex and dynamic barrier. It is formed by an interdependent network of brain capillary endothelial cells, endowed with barrier properties, and perivascular cells (astrocytes and pericytes) responsible for inducing and maintaining those properties. One of the primary properties of the BBB is a strict regulation of paracellular permeability due to the presence of junctional complexes (tight, adherens and gap junctions) between the endothelial cells. Alterations in junction assembly and function significantly affect BBB properties, particularly barrier permeability. However, such alterations are also involved in remodeling the brain endothelial cell surface and regulating brain endothelial cell phenotype. This review summarizes the characteristics of brain endothelial tight, adherens and gap junctions and highlights structural and functional alterations in junctional proteins that may contribute to BBB dysfunction.

The Role of Early Growth Response 1 (EGR1) in Brain Plasticity and Neuropsychiatric Disorders.

Abstract: It is now clearly established that complex interactions between genes and environment are involved in multiple aspects of neuropsychiatric disorders, from determining an individual’s vulnerability to onset, to influencing its response to therapeutic intervention. In this perspective, it appears crucial to better understand how the organism reacts to environmental stimuli and provide a coordinated and adapted response. In the central nervous system, neuronal plasticity and neurotransmission are among the major processes integrating such complex interactions between genes and environmental stimuli. In particular, immediate early genes are critical components of these interactions as they provide the molecular framework for a rapid and dynamic response to neuronal activity while opening the possibility for a lasting and sustained adaptation through regulation of the expression of a wide range of genes. As a result, immediate early genes have been tightly associated with neuronal activity as well as a variety of higher order processes within the central nervous system such as learning, memory, and sensitivity to reward. The immediate early gene and transcription factor early growth response 1 (EGR1) has thus been revealed as a major mediator and regulator of synaptic plasticity and neuronal activity in both physiological and pathological conditions. In this review, we will focus on the role of EGR1 in the central nervous system. First, we will summarize the different factors influencing its activity. Then, we will analyze the amount of data, including genome-wide, that has emerged in the recent years describing the wide variety of genes, pathways, and biological functions regulated directly or indirectly by EGR1. We will thus be able to gain better insights into the mechanisms underlying EGR1’s functions in physiological neuronal activity. Finally, we will discuss and illustrate the role of EGR1 in pathological states with a particular interest in cognitive functions and neuropsychiatric disorders.