Publications
121 results found
Singh M, Nabavi E, Zhou Y, et al., 2019, Laparoscopic fluorescence image-guided photothermal therapy enhances cancer diagnosis and treatment, Nanotheranostics, Vol: 3, Pages: 89-102, ISSN: 2206-7418
Endoscopy is the gold standard investigation in the diagnosis of gastrointestinal cancers and the management of early and pre-malignant lesions either by resection or ablation. Recently gold nanoparticles have shown promise in cancer diagnosis and therapeutics (theranostics). The combination of multifunctional gold nanoparticles with near infrared fluorescence endoscopy for accurate mapping of early or pre-malignant lesions can potentially enhance diagnostic efficiency while precisely directing endoscopic near infrared photothermal therapy for established cancers. The integration of endoscopy with near infrared fluorescence imaging and photothermal therapy was aided by the accumulation of our multifunctionalized PEG-GNR-Cy5.5-anti-EGFR-antibody gold nanorods within gastrointestinal tumor xenografts in BALB/c mice. Control mice (with tumors) received either gold nanorods or photothermal therapy, while study mice received both treatment modalities. Local (tumor-centric) and systemic effects were examined for 30 days. Clear endoscopic near infrared fluorescence signals were observed emanating specifically from tumor sites and these corresponded precisely to the tumor margins. Endoscopic fluorescence-guided near infrared photothermal therapy successfully induced tumor ablations in all 20 mice studied, with complete histological clearance and minimal collateral damage. Multi-source analysis from histology, electron microscopy, mass spectrometry, blood, clinical evaluation, psychosocial and weight monitoring demonstrated the inherent safety of this technology. The combination of this innovative nanotechnology with gold standard clinical practice will be of value in enhancing the early optical detection of gastrointestinal cancers and a useful adjunct for its therapy.
Ning J, Zhao H, Chen B, et al., 2019, Argon Mitigates Impaired Wound Healing Process and Enhances Wound Healing In Vitro and In Vivo, THERANOSTICS, Vol: 9, Pages: 477-490, ISSN: 1838-7640
Wang C, Datoo T, Zhao H, et al., 2018, Midazolam and Dexmedetomidine Affect Neuroglioma and Lung Carcinoma Cell Biology In Vitro and In Vivo, ANESTHESIOLOGY, Vol: 129, Pages: 1000-1014, ISSN: 0003-3022
Ma J, Chen Q, Li J, et al., 2018, Dexmedetomidine-Mediated Prevention of Renal Ischemia-Reperfusion Injury Depends in Part on Cholinergic Anti-Inflammatory Mechanisms., Anesth Analg
BACKGROUND: Organ ischemia-reperfusion injury often induces local and systemic inflammatory responses, which in turn worsen organ injury. These inflammatory responses can be regulated by the central nervous system, particularly by the vagal nerve and nicotinic acetylcholine receptors, which are the key components of cholinergic anti-inflammatory pathway. Activation of the cholinergic anti-inflammatory pathway can suppress excessive inflammatory responses and be a potential strategy for prevention of ischemia-reperfusion injury of organs including the kidney. METHODS: Vagal nerve activity, plasma acetylcholine, catecholamine and inflammatory mediators, renal tissue injury, and cell death were measured in mice with bilateral renal ischemia/reperfusion with or without treatment with dexmedetomidine (Dex), an α2-adrenergic receptor agonist. RESULTS: Dex significantly increased the discharge frequency of the cervical vagal nerve by up to 142 Hz (mean) (P < .001), and preserved kidney gross morphology and structure and attenuated cell apoptosis after ischemia-reperfusion. Furthermore, Dex also significantly increased acetylcholine release to 135.8 pmol/L (median) when compared to that (84.7 pmol/L) in the sham group (P < .001) and reduced the levels of several inflammatory mediators induced by renal ischemia/reperfusion. All the effects were abolished by vagotomy, splenectomy, or combinative administration of atipamezole, an α2-adrenergic receptor antagonist. CONCLUSIONS: Our findings suggest that Dex provides renoprotection, at least in part, through anti-inflammatory effects of the parasympathetic nervous system activation in addition to its direct actions on α2-adrenergic receptors.
Zhao H, Ma D, Huang H, et al., 2018, VEGF mitigates histone induced pyroptosis in the remote liver injury associated with renal allograft ischemia-reperfusion injury in rats, American Journal of Transplantation, Vol: 18, Pages: 1890-1903, ISSN: 1600-6135
Clinical evidence indicated a possible link between renal injury and remote liver injury. Herein, we investigated whether extracellular histone mediates remote hepatic damage following renal graft ischemia-reperfusion injury, whilst vascular endothelial growth factor (VEGF) is protective against remote hepatic injury. In vitro, hepatocyte HepG2 cultures were treated with histone. In vivo, the Brown-Norway renal graft was stored in 4°C preserving solution for 24 hours and then transplanted into Lewis rat recipient; blood samples and livers from recipients were harvested 24 hours after surgery. Prolonged cold ischemia in renal grafts enhanced liver injury 24 hours after engraftment. Caspase-1, ASC, NLRP3 and AIM2 expression in hepatocyte, CD68+ infiltrating macrophages, tissue and serum IL-1β and IL-18 were greatly elevated, indicating that pyroptosis occurred in the liver and resulted in acute liver functional impairment. Blocking caspase-1 pathway decreased the number of necrotic hepatocytes. VEGF treatment suppressed the hepatocyte pyroptosis and liver function was partially restored. Our data suggested that renal allograft ischemia-reperfusion injury is likely associated with acute liver damage due to hepatocyte pyroptosis induced by histone and such injury may be protected by VEGF administration. VEGF, therefore, may serve as a new strategy against other remote organ injuries related to renal transplant.
Sun Y, Zhao H, Wang D, et al., 2018, Dexmedetomidine alleviates LPS-induced pyroptosis in astrocytes in vitro, BJA Research Forum, Publisher: ELSEVIER SCI LTD, Pages: E8-E9, ISSN: 0007-0912
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- Citations: 3
Zhao H, Chen Q, Alam A, et al., 2018, The role of osteopontin in the progression of solid organ tumour, Cell Death and Disease, Vol: 9, ISSN: 2041-4889
Osteopontin (OPN) is a bone sialoprotein involved in osteoclast attachmentto mineralised bone matrix, as well as being a bone matrix protein, OPN isalso a versatile protein that acts on various receptors which are associatedwith different signalling pathways implicated in cancer. OPN mediatesvarious biological events involving the immune system and the vascularsystem; the protein plays a role in processes such as immune response, celladhesion and migration, and tumorigenesis. This review discusses thepotential role of OPN in tumour cell proliferation, angiogenesis andmetastasis, as well as the molecular mechanisms involved in theseprocesses in different cancers, including brain, lung, kidney, liver, bladder,breast, oesophageal, gastric, colon, pancreatic, prostate and ovarian cancers.The understanding of OPN’s role in tumour development and progressioncould potentially influence cancer therapy and contribute to thedevelopment of novel anti-tumour treatments.
Zhao H, Alam A, Pac Soo A, et al., 2018, Ischemia-reperfusion injury reduces long term renal graft survival: mechanism and beyond, EBioMedicine, Vol: 28, Pages: 31-42, ISSN: 2352-3964
Ischemia-reperfusion injury (IRI) during renal transplantation often initiates non-specific inflammatory responses that can result in the loss of kidney graft viability. However, the long-term consequence of IRI on renal grafts survival is uncertain. Here we review clinical evidence and laboratory studies, and elucidate the association between early IRI and later graft loss. Our critical analysis of previous publications indicates that early IRI does contribute to later graft loss through reduction of renal functional mass, graft vascular injury, and chronic hypoxia, as well as subsequent fibrosis. IRI is also known to induce kidney allograft dysfunction and acute rejection, reducing graft survival. Therefore, attempts have been made to substitute traditional preserving solutions with novel agents, yielding promising results.
Singh M, Nabavi E, Zhou Y, et al., 2018, Fluorescence image-guided photothermal therapy: Diagnosis and treatment of upper gastrointestinal cancer and beyond (prize winner), Global Surgery
Ciechanowicz S, Zhao H, Chen Q, et al., 2018, Differential effects of sevoflurane on the metastatic potential and chemosensitivity of non-small-cell lung adenocarcinoma and renal cell carcinoma <i>in vitro</i>, BRITISH JOURNAL OF ANAESTHESIA, Vol: 120, Pages: 368-375, ISSN: 0007-0912
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- Citations: 48
Zhao H, Rossaint R, Coburn M, et al., 2017, The renoprotective properties of xenon and argon in kidney transplantation, EUROPEAN JOURNAL OF ANAESTHESIOLOGY, Vol: 34, Pages: 637-640, ISSN: 0265-0215
Zhao H, Ma D, Alam A, 2017, EXPOSURE TO ARGON AT EX VIVO STAGE PROTECTS RAT DCD RENAL ALLOGRAFT AGAINST ISCHEMIC-HYPOTHERMIC INJURY, Publisher: WILEY, Pages: 66-66, ISSN: 0934-0874
Suen KC, Zhao H, Ma D, 2017, Histone release mediated necroptosis in remote lung injury following renal allograft ischemia-reperfusion injury in rats, British Journal of Anaesthesia (BJA) Research Forum, Publisher: OXFORD UNIV PRESS, Pages: E25-E25, ISSN: 0007-0912
Zhao H, Chen Q, Suen K, et al., 2017, Osteopontin mediates necroptosis in remote lung injury after receiving ischemic renal allografts in rats, British Journal of Anaesthesia (BJA) Research Forum, Publisher: OXFORD UNIV PRESS, Pages: E29-E29, ISSN: 0007-0912
Chen Q, Zhao H, Gu J, et al., 2017, Dexmedetomidine modulates lung alveolar macrophage polarization in vitro, British Journal of Anaesthesia (BJA) Research Forum, Publisher: OXFORD UNIV PRESS, Pages: E25-E26, ISSN: 0007-0912
Zhao H, Alam A, San C-Y, et al., 2017, Molecular mechanisms of brain-derived neurotrophic factor in neuroprotection: Recent developments, BRAIN RESEARCH, Vol: 1665, Pages: 1-21, ISSN: 0006-8993
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- Citations: 81
Silk E, Zhao H, Weng H, et al., 2017, The role of extracellular histone in organ injury, Cell Death & Disease, Vol: 8, ISSN: 2041-4889
Histones are intra-nuclear cationic proteins that are present in all eukaryotic cells and are highly conserved acrosss pecies. Within the nucleus, they provide structural stability to chromatin and regulate gene expression. Histone may be released into the extracellular space in three forms: freely, as a DNA-bound nucleosome or as part of neutrophilextracellular traps, and all three can be deteted in serum after significant cellular death such as sepsis, trauma, ischaemia/reperfusion (I/R) injury and autoimmune disease. Once in the extracellular space, histones actas Damage-Associated Molecular Pattern (DAMP) proteins,activating theimmune system and causing further cytotoxicity. They interact with Toll-Like Receptors (TLRs), complement and the phospholipids of cell membranes inducing endothelial and epithelial cytotoxicity, TLR2/TLR4/TLR9 activation and pro-inflammatory cytokine/chemokine release via MyD88, NFκB and NLRP3 inflammasome dependent pathways. Drugs that block the release of histone, neutralise circulating histone or block histone signal transduction provide significant protection from mortality in animal models of acute organinjury but warrant further research to in form future clinical applications.
Ma D, Zhao H, 2017, Differential effects of sevoflurane on the metastatic potential and chemosensitivity of non-small-cell lung adenocarcinoma and renal cell carcinoma in vitro., Br J Anaesth
Wang L, Qin W, Zhou Y, et al., 2017, Transforming growth factor β plays an important role in enhancing wound healing by topical application of Povidone-iodine, SCIENTIFIC REPORTS, Vol: 7, ISSN: 2045-2322
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- Citations: 44
Zhao H, Alam A, Chen Q, et al., 2017, The role of microglia in the pathobiology of neuropathic pain development: what do we know?, BRITISH JOURNAL OF ANAESTHESIA, Vol: 118, Pages: 504-516, ISSN: 0007-0912
Zhao H, Eguchi S, Alam A, et al., 2017, The role of nuclear factor-erythroid 2 related factor 2 (Nrf-2) in the protection against lung injury, AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, Vol: 312, Pages: L155-L162, ISSN: 1040-0605
Chen L, Zhao H, Yao S, et al., 2016, Epithelium-macrophage interaction promotes epithelial-to-mesenchymal transition after chemotherapy, BJA Research Forum, Publisher: OXFORD UNIV PRESS, Pages: E839-E840, ISSN: 0007-0912
Hu C, Wu L, Zhao H, et al., 2016, RIPK1 and RIPK3 mediated necroptosis in hypoxic-ischaemic encephalopathy in rats, BJA Research Forum, Publisher: ELSEVIER SCI LTD, Pages: E846-E847, ISSN: 0007-0912
Li T, Cui J, Zhao H, et al., 2016, Bupivacaine and levobupivacaine inhibit colon cancer but not melanoma cell malignancy <i>in vitro</i>: possible role of endoplasmic reticulum stress, BJA Research Forum, Publisher: OXFORD UNIV PRESS, Pages: E840-E841, ISSN: 0007-0912
Zhao H, Eguchi S, Alam A, et al., 2016, The role of nuclear factor-erythroid 2 related factor 2 (Nrf-2) in the protection against lung injury., American Journal of Physiology-Lung Cellular and Molecular Physiology, ISSN: 1522-1504
Nuclear factor-erythroid 2 related factor 2 (Nrf2) is a ubiquitous master transcription factor that upregulates antioxidant response elements (AREs)-mediated expression of antioxidant enzyme and cytoprotective proteins. Activation of Nrf2 has been shown to be protective against lung injury. In the lung, diverse stimuli including environmental oxidants, medicinal agents and pathogens can activate Nrf2. Nrf2 translocates to the nucleus and binds to an antioxidant response element (ARE). Through transcriptional induction of ARE-bearing genes encoding antioxidant-detoxifying proteins, Nrf2 induces cellular rescue pathways against oxidative pulmonary injury, abnormal inflammatory and immune responses, and apoptosis. The Nrf2-antioxidant pathway has been shown to be important in the protection against various lung injury including acute lung injury/acute respiratory distress syndrome and bronchopulmonary dysplasia, chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, asthma and allergy, and was widely examined for new therapeutic targets. The current review explores the protective role of Nrf-2 against lung injury and the therapeutic potential in targeting Nrf-2.
Cui J, Zhao H, Ma D, 2016, Propofol reduces acute lymphoblastic leukaemia malignancy through production of reactive oxygen species and downregulation of osteopontin receptor in vitro, Meeting of the Difficult-Airway-Society, Publisher: OXFORD UNIV PRESS, Pages: E929-E929, ISSN: 0007-0912
Alam A, Zhao H, Ma D, 2016, Potential protective effects of argon on renal graft <i>in vitro</i> and <i>ex vivo</i>, Meeting of the Difficult-Airway-Society, Publisher: ELSEVIER SCI LTD, Pages: E934-E934, ISSN: 0007-0912
Wu L, Zhao H, Ma D, 2016, Small intestinal injury after injurious renal allograft transplantation in rats, Meeting of the Difficult-Airway-Society, Publisher: OXFORD UNIV PRESS, Pages: E934-E935, ISSN: 0007-0912
Ciechanowicz S, Zhao H, Ma D, 2016, Differential effects of sevoflurane on malignant potential of non-small-cell lung adenocarcinoma and renal cell carcinoma <i>in vitro</i>, Meeting of the Difficult-Airway-Society, Publisher: OXFORD UNIV PRESS, Pages: E929-E930, ISSN: 0007-0912
Zhao H, Kilgas S, Alam A, et al., 2016, The Role of Extracellular Adenosine Triphosphate in Ischemic Organ Injury., Critical Care Medicine, Vol: 44, Pages: 1000-1012, ISSN: 1530-0293
OBJECTIVES: Ischemic tissue injury contributes to significant morbidity and mortality and is implicated in a range of pathologic conditions, including but not limited to myocardial infarction, ischemic stroke, and acute kidney injury. The associated reperfusion phase is responsible for the activation of the innate and adaptive immune system, further accentuating inflammation. Adenosine triphosphate molecule has been implicated in various ischemic conditions, including stroke and myocardial infarction. STUDY SELECTION: Adenosine triphosphate is a well-defined intracellular energy transfer and is commonly referred to as the body's "energy currency." However, Laboratory studies have demonstrated that extracellular adenosine triphosphate has the ability to initiate inflammation and is therefore referred to as a damage-associated molecular pattern. Purinergic receptors-dependent signaling, proinflammatory cytokine release, increased Ca influx into cells, and subsequent apoptosis have been shown to form a common underlying extracellular adenosine triphosphate molecular mechanism in ischemic organ injury. CONCLUSIONS: In this review, we aim to discuss the molecular mechanisms behind adenosine triphosphate-mediated ischemic tissue injury and evaluate the role of extracellular adenosine triphosphate in ischemic injury in specific organs, in order to provide a greater understanding of the pathophysiology of this complex process. We also appraise potential future therapeutic strategies to limit damage in various organs, including the heart, brain, kidneys, and lungs.
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