Haobo Li

Massachusetts General Hospital and Harvard Medical School · Cardiovascular Research Center

Hyperglycemia-induced oxidative stress is implicated in the development of cardiomyopathy in diabetes that is associated with reduced adiponectin (APN) and heme oxygenase-1 (HO-1). Brahma-related gene 1 (Brg1) assists nuclear factor-erythroid-2-related factor-2 (Nrf2) to activate HO-1 to increase myocardial antioxidant capacity in response to oxida...

Signal transducer and activator of transcription-3(STAT3) activation is key for ischemic postconditioning(IPo) to attenuate myocardial ischemia-reperfusion injury(MIRI), but IPo loses cardioprotection in diabetes whose cardiac STAT3 activation is impaired and adiponectin reduced. We found that IPo increased post-ischemic cardiomyocyte-derived adipo...

Myocardial ischaemia reperfusion injury is the leading cause of death in patients with cardiovascular disease. Interventions such as ischaemic pre and postconditioning protect against myocardial ischaemia reperfusion injury. Certain anaesthesia drugs and opioids can produce the same effects, which led to an initial flurry of excitement given the ex...

During aging, deterioration in cardiac structure and function leads to increased susceptibility to heart failure. The need for interventions to combat this age-related cardiac decline is becoming increasingly urgent as the elderly population continues to grow. Our understanding of cardiac aging, and aging in general, is limited. However, recent stu...

Background: The heart grows in response to pathological and physiological stimuli. The former often precedes cardiomyocyte loss and heart failure; the latter paradoxically protects the heart and enhances cardiomyogenesis. The mechanisms underlying these differences remain incompletely understood. While long noncoding RNAs (lncRNAs) are important i...

Background and purpose: Acute lung injury (ALI) is a serious, life-threatening inflammation of the lungs with a lack of effective treatment. We previously showed that serine protease inhibitor B1 (SerpinB1) protects against ALI induced by orthotopic autologous liver transplantation. However, the role of SerpinB1 in lipopolysaccharide (LPS) -induce...

Inhalation of xenon gas improves acute kidney injury (AKI). However, xenon can only be delivered through inhalation, which causes non-specific distribution and low bioavailability of xenon, thus limiting its clinical application. In this study, xenon is loaded into platelet membrane-mimicking hybrid microbubbles (Xe-Pla-MBs). In ischemia-reperfusio...

Cardiomyocytes comprise ∼70% to 85% of the total volume of the adult mammalian heart but only about 25% to 35% of its total number of cells. Advances in single cell (sc) and single nuclei (sn) RNA sequencing (scRNA-seq and snRNA-seq) have greatly facilitated investigation into and increased appreciation of the potential functions of non-cardiomyocy...

Background: Exercise promotes cardioprotective benefits for the adult heart; however, the exercise-induced molecular and microstructural remodeling processes have yet to be fully characterized. This study sought to define the spatial interactions between molecular and microstructural remodeling that are induced by exercise and might result in cardi...

Background: Osimertinib is a third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) for non-small cell lung cancer (NSCLC) treatment. Osimertinib potently and selectively inhibits EGFR-T790M resistance mutations in patients with NSCLC harboring these mutations. Emerging evidence from clinical trials has identified po...

Background: The human heart has limited capacity to generate new cardiomyocytes and this capacity declines with age. Because loss of cardiomyocytes may contribute to heart failure, it is crucial to explore stimuli of endogenous cardiac regeneration to favorably shift the balance between loss of cardiomyocytes and the birth of new cardiomyocytes in...

Both exercise-induced molecular mechanisms and physiological cardiac remodeling have been previously studied on a whole heart level. However, the regional microstructural tissue effects of these molecular mechanisms in the heart have yet to be spatially linked and further elucidated. We show in exercised mice that the expression of CITED4, a transc...

Acute and chronic animal models of exercise are commonly used in research. Acute exercise testing is used, often in combination with genetic, pharmacological, or other manipulations, to study the impact of these manipulations on the cardiovascular response to exercise and to detect impairments or improvements in cardiovascular function that may not...

Extracellular tRNA‐Derived Small RNAs In article number 2200829, Saumya Das and co‐workers provide a comprehensive landscape for the signature of cellular and extracellular tRNA‐derived small RNAs (tDRs) in response to different stressors. They also determine a distinct fragmentation pattern for extracellular tDRs distinct from cellular tDRs and in...

The cellular response to stress is an important determinant of disease pathogenesis. Uncovering the molecular fingerprints of distinct stress responses may identify novel biomarkers and key signaling pathways for different diseases. Emerging evidence shows that transfer RNA‐derived small RNAs (tDRs) play pivotal roles in stress responses. However,...

Introduction: CITED4 (CBP/p300-interacting transactivators with E [glutamic acid]/D [aspartic acid]-rich-carboxylterminal domain 4) is a transcriptional regulator which limits pathologic remodeling after ischemic and pressure overload models of cardiac stress. It is also upregulated in the heart with exercise, an effective intervention which induce...

The cellular response to stress is an important determinant of disease pathogenesis. Uncovering the molecular fingerprints of distinct stress responses may yield novel biomarkers for different diseases, and potentially identify key signaling pathways important for disease progression. tRNAs and tRNA-derived small RNAs (tDRs) comprise one of the mos...

Heart failure (HF) remains the leading cause of morbidity and mortality in the US, affecting approximately 6.2 million Americans with an anticipated 46% increase in overall prevalence by 2030. Myocardial fibrosis, defined as increased cardiac fibroblast (CF) activation and excessive extracellular matrix (ECM) deposition, is a leading contributor to...

Background and purpose: Macrophages regulate iron homeostasis in the liver and play important role in hepatic ischemia/reperfusion (I/R) injury. The aim of this study was to explore the role of macrophages in iron overload-related hepatocyte damage during liver I/R. Experimental approach: Liver biopsys from patients undergoing partial hepatectom...

Spinal cord injury (SCI) impairs mobility and often results in complications like intractable neuropathic pain. A multi-approach management of this chronic pain condition has been encouraged, but little has been explored of the field. Here, we focus on the effect and underlying mechanism of environmental enrichment (EE), which promotes voluntary so...

Rationale: Pathological hypertrophy commonly leads to heart failure (HF) and loss of cardiomyocytes, while physiological hypertrophy protects the heart and enhances cardiomyogenesis. The mechanisms underlying these differences remain unclear. While long noncoding RNAs (lncRNAs) are important in cardiac development and disease, their role in physiol...

Ischemia–reperfusion (I/R) injury is common during surgery and often results in organ dysfunction. The mechanisms of I/R injury are complex, diverse, and not well understood. RNA methylation is a novel epigenetic modification that is involved in the regulation of various biological processes, such as immunity, response to DNA damage, tumorigenesis,...

Heart failure with preserved ejection fraction (HFpEF) is the most common type of HF in older adults. Although no pharmacological therapy has yet improved survival in HFpEF, exercise training (ExT) has emerged as the most effective intervention to improving functional outcomes in this age‐related disease. The molecular mechanisms by which ExT induc...

Myocardial ischemic postconditioning- (IPo-) mediated cardioprotection against myocardial ischemia-reperfusion (IR) injury needs the activation of signal transducer and activator of transcription 3 (STAT3), which involves adiponectin (APN). APN confers its biological effects through AMP-activated protein kinase- (AMPK-) dependent and AMPK-independe...

Sepsis-related acute kidney injury (AKI) is known to be caused by inflammation. We explored the renal protective effects of aerosol inhalation of a hydrogen-rich solution (HRS; hydrogen gas dissolved to saturation in saline) in a mouse model of septic AKI. Septic AKI was induced through 18 hours of cecal ligation and puncture. AKI occurred during t...

Background: Neutrophil infiltration plays a critical role in the pathogenesis of acute lung injury following liver transplantation (LT). Neutrophil elastase is released from neutrophils during pulmonary polymorphonuclear neutrophil activation and sequestration. The aim of the study was to investigate whether the inhibition of neutrophil elastase c...

Long noncoding-RNAs (lncRNAs) are critical regulators of cardiac development as well as pathological hypertrophy and heart failure (HF). However, their roles in exercise-induced physiological hypertrophy are unclear. Here, we used RNAseq to identify a novel class of cardiac lncRNAs that are dynamically regulated by exercise. We call these l ong n o...

Ischemia postconditioning (PTC) can reduce myocardial ischemia/reperfusion injury. However, the effectiveness of PTC cardioprotection is reduced or lost in diabetes and the mechanisms are largely unclear. Hyperglycemia can induce overexpression of inducible nitric oxide synthesis (iNOS) in the myocardium of diabetic subjects. However, it is unknown...

Nonalcoholic fatty liver disease (NAFLD) is a common liver disease which has been previously shown to be associated with type 2 diabetes mellitus (T2DM). Recent research has indicated that type 1 diabetes mellitus (T1DM) is also involved in the development of nonalcoholic fatty liver disease, whereas the underlying mechanisms are largely unknown. F...

Background: Physiological cardiac hypertrophy occurs commonly in response to exercise and can protect against pathological stress. In contrast, pathological hypertrophy occurs in disease and often precedes heart failure . Although physiological and pathological hypertrophy often involve distinct signaling mechanisms, miR-222 is an exercise-induced...

Endothelin-1 (ET-1) and its receptors (ETAR/ETBR) emerge to be a key signaling axis in neuropathic pain processing and are recognized as new therapeutic targets. Yet, little is known on the functional regulation of ET-1 axis during neuropathic pain. Bioinformatics analysis indicated that paired box gene 2 (Pax2) or nuclear factor of activated T-cel...

Background/aims: Protein kinase C(PKC)-ε activation is a mechanism of preconditioning cardioprotection but its role in repeated non-invasive limb ischemic preconditioning (rNLIP) mediated cardioprotection against myocardial ischemia/reperfusion (I/R) injury in diabetes is unknown. Methods: Eight-week streptozotocin-induced diabetic and non-diabe...

Background: Adiponectin, a cytokine secreted by adipocytes, plays an important role in regulating glucose and lipid metabolism. However, the role of adiponectin in pain conditions is largely unknown. This study aimed to identify the role and mechanism of adiponectin in nociceptive sensitivity under physiological and pathological states utilising ad...

Background/aims: Hearts from diabetic subjects are susceptible to myocardial ischemia reperfusion (I/R) injury. Propofol has been shown to protect against myocardial I/R injury due to its antioxidant properties while the underlying mechanism remained incompletely understood. Thus, this study aimed to determine whether or not propofol could attenua...

Background: This study aimed to evaluate the protective effect and mechanisms of remote limb ischaemic postconditioning (RIPostC) against myocardial ischaemia/reperfusion (IR) injury. Methods: Male mice underwent 45 min of coronary artery occlusion followed by 2 h of reperfusion. RIPostC was achieved by three cycles of 5 min of ischaemia and 5 m...

Figure S1 Identify of the rhMG53 protein and its functional test against cell membrane damage. A, SDS‐PAGE and western blot were carried out to show the purity and identify of the His‐MG53 protein in different protein contents. B, The functional test of rhMG53 was evaluated by using H/R‐induced AML12 hepatocytes. Different hypoxia/reoxygenation (H/...

Both oxidative stress and mast cell (MC) degranulation participate in the process of small intestinal ischemia reperfusion (IIR) injury, and oxidative stress induces MC degranulation. Propofol, an anesthetic with antioxidant property, can attenuate IIR injury. We postulated that propofol can protect against IIR injury by inhibiting oxidative stress...

Cytoprotective gene heme oxygenase 1 (HO-1) could be induced by nuclear factor E2-related factor 2 (Nrf2) nuclear translocation. The purpose of this study was to determine the role of Brahma-related gene 1 (Brg1), a catalytic subunit of SWI2/SNF2-like chromatin remodeling complexes, in Nrf2/HO-1 pathway activation during hepatic ischemia-reperfusio...

Cytoprotective gene heme oxygenase 1 (HO-1) could be induced by nuclear factor E2-related factor 2 (Nrf2) nuclear translocation. The purpose of this study was to determine the role of Brahma-related gene 1 (Brg1), a catalytic subunit of SWI2/SNF2-like chromatin remodeling complexes, in Nrf2/HO-1 pathway activation during hepatic ischemia–reperfusio...

Hepatic ischaemia/reperfusion (HIR) induces severe damage on hepatocyte cell membrane, which leads to hepatocyte death and the subsequent HIR injury. In this study, we investigated the role and the mechanism of mitsugumin-53 (MG53), a novel cell membrane repair protein, in protecting the liver against HIR injury. Rats were subjected to sham operati...

Background: Postoperative acute lung injury(ALI) is a severe complication after liver transplantation, which severely affects postoperative patients' survival. The underlying mechanism is largely unknown and effective treatment limited. We explored the role of serpin protease inhibitor B1(SERPINB1), a potent inhibitor of neutrophil serine protease...

Aims: Remote ischaemic preconditioning (RIPC) by inducing brief ischaemia in distant tissues protects the heart against myocardial ischaemia-reperfusion injury (IRI) in children undergoing open-heart surgery, although its effectiveness in adults with comorbidities is controversial. The effectiveness and mechanism of RIPC with respect to myocardial...

Background . Excessive autophagy is a major mechanism of myocardial ischemia reperfusion injury (I/RI) in diabetes with enhanced oxidative stress. Antioxidant N-acetylcysteine (NAC) reduces myocardial I/RI. It is unknown if inhibition of autophagy may represent a mechanism whereby NAC confers cardioprotection in diabetes. Methods and Results . Diab...

Necrosis amplifies inflammation and plays important roles in acute respiratory distress syndrome (ARDS). Necroptosis is a newly identified programmed necrosis that is mediated by receptor interacting protein 3 (RIP3). However, the potential involvement and impact of necroptosis in lipopolysaccharide (LPS)-induced ARDS remains unknown. We therefore...

Diabetic cardiomyopathy (DCM) is a disorder of the heart muscle in people with diabetes that can occur independent of hypertension or vascular disease. The underlying mechanism of DCM is incompletely understood. Some transcription factors have been suggested to regulate the gene program intricate in the pathogenesis of diabetes prompted cardiac inj...

Sevofluane postconditioning (SPostC) protects heart against ischemia/reperfusion injury. However, SPostC cardioprotection is lost in diabetes whose cardiac heme oxygenase-1 (HO-1) is reduced. Brahma-related gene 1 (Brg1) facilitates nuclear factor-erythroid-2-related factor-2 (Nrf2) to activate HO-1 to increase myocardial antioxidant capacity in re...

Isoflurane postconditioning(IsoPostC) attenuates myocardial ischemia-reperfusion injury. STAT3 is critical in ischemic postconditioning cardioprotection, which can be regulated by Brg1 and Nrf2. However, Brg1 and Nrf2 are reduced in diabetic hearts. We hypothesized that reduced Brg1/Nrf2 and STAT3 activation may jeopardize IsoPostC-mediated cardiop...

Oxidative stress plays a critical role in the pathogenesis of intestinal ischemia reperfusion (IIR) injury. Enhancement in endogenous Lipoxin A4 (LXA4), a potent antioxidant and mediator, is associated with attenuation of IIR. However, the effects of LXA4 on IIR injury and the potential mechanisms are unknown. In a rat IIR (ischemia 45 minutes and...

The present study explored the potential causal link between ischemia-driven cyclooxygenase-2 (COX-2) expression and enhanced apoptosis during myocardial ischemia/reperfusion (I/R) by using H9C2 cardiomyocytes and primary rat cardiomyocytes subjected to hypoxia/reoxygenation (H/R). The results showed that H/R resulted in higher COX-2 expression tha...