Imperial College London

Dr Hailin Zhao

Faculty of MedicineDepartment of Surgery & Cancer

Research Associate
 
 
 
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Contact

 

hailin.zhao06

 
 
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Location

 

Chelsea and Westminster HospitalChelsea and Westminster Campus

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Summary

 

Publications

Publication Type
Year
to

106 results found

Huang H, Liu P, Ma D, Zhang H, Xu H, Zhou J, Zhao H, Zhao T, Li Cet al., 2022, Triiodothyronine attenuates neurocognitive dysfunction induced by sevoflurane in the developing brain of neonatal rats, JOURNAL OF AFFECTIVE DISORDERS, Vol: 297, Pages: 455-462, ISSN: 0165-0327

Journal article

Ma D, 2022, Methionine restriction prevents lipopolysaccharide-inducedacute lung injury via modulating CSE/H2S pathway, Nutrients, Vol: 14, Pages: 1-15, ISSN: 2072-6643

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) result in high mortality, whereas effective treatments are limited. Methionine restriction (MR) has been reported to offer various benefits against multiple pathological processes of organ injuries. However, it remains unknown whether MR has any potential therapeutic value for ALI/ARDS. The current study was set to investigate the therapeutic potential of MR on lipopolysaccharide (LPS)-induced ALI and its underlying mechanisms. We found that MR attenuated LPS-induced pulmonary edema, hemorrhage, atelectasis, and alveolar epithelial cell injuries in mice. MR upregulated cystathionine-gamma-lyase (CSE) expression and enhanced the production of hydrogen sulfide (H2S). MR also inhibited the activation of Toll-like receptors 4 (TLR4)/NF-κB/NOD-like receptor protein 3 (NLRP3), then reduced IL-1β, IL-6, and TNF-α release and immune cell infiltration. Moreover, the protective effects of MR on LPS-induced ALI were abrogated by inhibiting CSE, whereas exogenous H2S treatment alone mimicked the protective effects of MR in Cse−/− mice after LPS administration. In conclusion, our findings showed that MR attenuated LPS-induced lung injury through CSE and H2S modulation. This work suggests that developing MR towards clinical use for ALI/ARDS patients may be a valuable strategy.

Journal article

Liu L, Sun Q, Davis F, Mao J, Zhao H, Ma Det al., 2022, Epithelial-mesenchymal transition in organ fibrosis development: current understanding and treatment strategies, BURNS & TRAUMA, Vol: 10, ISSN: 2321-3868

Journal article

Chen Q, Qin Z, Sun Y, Liu X, Soo AP, Chang E, Sun Q, Yi B, Wang D-X, Zhao H, Ma D, Gu Jet al., 2022, Dexmedetomidine Activates Akt, STAT6 and IRF4 Modulating Cytoprotection and Macrophage Anti-Inflammatory Phenotype Against Acute Lung Injury in vivo and in vitro, JOURNAL OF INFLAMMATION RESEARCH, Vol: 15, Pages: 2707-2720

Journal article

Chen L, Alam A, Pac-Soo A, Chen Q, Shang Y, Zhao H, Yao S, Ma Det al., 2021, Pretreatment with valproic acid alleviates pulmonary fibrosis through epithelial-mesenchymal transition inhibition in vitro and in vivo, LABORATORY INVESTIGATION, Vol: 101, Pages: 1166-1175, ISSN: 0023-6837

Journal article

Ishikawa M, Iwasaki M, Zhao H, Saito J, Hu C, Sun Q, Sakamoto A, Ma Det al., 2021, Inhalational Anesthetics Inhibit Neuroglioma Cell Proliferation and Migration via miR-138,-210 and-335, INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, Vol: 22

Journal article

Ishikawa M, Iwasaki M, Zhao H, Saito J, Hu C, Sun Q, Sakamoto A, Ma Det al., 2021, Sevoflurane and Desflurane Exposure Enhanced Cell Proliferation and Migration in Ovarian Cancer Cells via miR-210 and miR-138 Downregulation, INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, Vol: 22

Journal article

Zhao H, Davies R, Ma D, 2021, Potential therapeutic value of dexmedetomidine in COVID-19 patients admitted to ICU., Br J Anaesth, Vol: 126, Pages: e33-e35

Journal article

Iwasaki M, Saito J, Zhao H, Sakamoto A, Hirota K, Ma Det al., 2020, Inflammation Triggered by SARS-CoV-2 and ACE2 Augment Drives Multiple Organ Failure of Severe COVID-19: Molecular Mechanisms and Implications, INFLAMMATION, Vol: 44, Pages: 13-34, ISSN: 0360-3997

Journal article

Zhen C, Zhao H, Wu L, Alam A, Eguchi S, Weng H, Ma Det al., 2020, The Role of Neutrophil NETosis in Organ Injury: Novel Inflammatory Cell Death Mechanisms, INFLAMMATION, Vol: 43, Pages: 2021-2032, ISSN: 0360-3997

Journal article

Yang S-R, Hua K-F, Chu LJ, Hwu Y-K, Yang S-M, Wu C-Y, Lin T-J, Weng J-C, Zhao H, Hsu W-H, Liu F-C, Liaw W-J, Ma D, Ka S-M, Chen Aet al., 2020, Xenon blunts NF-kappa B/NLRP3 inflammasome activation and improves acute onset of accelerated and severe lupus nephritis in mice, KIDNEY INTERNATIONAL, Vol: 98, Pages: 378-390, ISSN: 0085-2538

Journal article

Zhang W, Sheng B, Chen S, Zhao H, Wu L, Sun Y, Cui J, Zhu X, Ma Det al., 2020, Sevoflurane Enhances Proliferation, Metastatic Potential of Cervical Cancer Cells via the Histone Deacetylase 6 Modulation In Vitro, ANESTHESIOLOGY, Vol: 132, Pages: 1469-1481, ISSN: 0003-3022

Journal article

Hu C, Huang Y, Wu L, Zhao H, Pac Soo C, Lian Q, Ma Det al., 2020, Apoptosis and necroptosis occur in the different brain regions of hippocampus in a rat model of hypoxia asphyxia, INTERNATIONAL JOURNAL OF NEUROSCIENCE, Vol: 131, Pages: 843-853, ISSN: 0020-7454

Journal article

Hu C, Liu Z, Zhao H, Wu L, Lian Q, Ma D, Li JVet al., 2020, A biochemical comparison of the lung, colonic, brain, renal, and ovarian cancer cell lines using 1H-NMR spectroscopy, Bioscience Reports, Vol: 40, ISSN: 0144-8463

Cancer cell lines are very often used for cancer research. However, continuous genetic instability-induced heterogeneity of cell lines can hinder the reproducibility of cancer research. Molecular profiling approaches including transcriptomics, chromatin modification profiling and proteomics are used to evaluate the phenotypic characteristics of cell lines. However, these do not reflect the metabolic function at the molecular level. Metabolic phenotyping is a powerful tool to profile the biochemical composition of cell lines. In this study, 1H-NMR spectroscopy-based metabolic phenotyping was used to detect metabolic differences among 5 cancer cell lines, namely, lung (A549), colonic (Caco2), brain (H4), renal (RCC), and ovarian (SKOV3) cancer cells. The concentrations of choline, creatine, lactate, alanine, fumarate and succinate varied remarkably among different cell types.The significantly higher intracellular concentrations of glutathione, myo-inositol, and phosphocholine were found in the SKOV3 cell line relative to other cell lines. Glutamate is higher in both SKOV3 and RCC cells compared to other cell lines. For cell culture media analysis, isopropanol was found to be the highest in RCC media, followed by A549 and SKOV3 media, while acetone was the highest in A549, followed by RCC and SKOV3. These results demonstrated that 1H-NMR-based metabolic phenotyping approach allows us to characterize specific metabolic signatures of cancer cell lines and provides phenotypical information of cellular metabolism.

Journal article

Zhao H, Chen Q, Huang H, Suen KC, Alam A, Cui J, Ciechanowicz S, Ning J, Lu K, Takata M, Gu J, Ma Det al., 2019, Osteopontin mediates necroptosis in lung injury after transplantation of ischaemic renal allografts in rats, BRITISH JOURNAL OF ANAESTHESIA, Vol: 123, Pages: 519-530, ISSN: 0007-0912

Journal article

Duan J, Yang Z, Huang J, Zhu Y, Zhao H, Unwith S, Gao X, Lu K, Ning Jet al., 2019, Inhibition of tyrosine kinases protects against lipopolysaccharide-induced acute lung injury by preventing nuclear export of Nrf2, JOURNAL OF CELLULAR BIOCHEMISTRY, Vol: 120, Pages: 12331-12339, ISSN: 0730-2312

Journal article

Wu L, Zhao H, Weng H, Ma Det al., 2019, Lasting effects of general anesthetics on the brain in the young and elderly: "mixed picture" of neurotoxicity, neuroprotection and cognitive impairment, JOURNAL OF ANESTHESIA, Vol: 33, Pages: 321-335, ISSN: 0913-8668

Journal article

Chen L, Zhao H, Alam A, Mi E, Eguchi S, Yao S, Ma Det al., 2019, Postoperative remote lung injury and its impact on surgical outcome, BMC ANESTHESIOLOGY, Vol: 19, ISSN: 1471-2253

Journal article

Sun Y-B, Zhao H, Mu D-L, Zhang W, Cui J, Wu L, Alam A, Wang D-X, Ma Det al., 2019, Dexmedetomidine inhibits astrocyte pyroptosis and subsequently protects the brain in in vitro and in vivo models of sepsis, Cell Death and Disease, Vol: 10, ISSN: 2041-4889

Sepsis is life-threatening and often leads to acute brain damage. Dexmedetomidine, an α2-adrenoceptor agonist, has been reported to possess neuroprotective effects against various brain injury but underlying mechanisms remain elusive. In this study, in vitro and in vivo models of sepsis were used to explore the effects of dexmedetomidine on the inflammasome activity and its associated glia pyroptosis and neuronal death. In vitro, inflammasome activation and pyroptosis were found in astrocytes following lipopolysaccharide (LPS) exposure. Dexmedetomidine significantly alleviated astrocyte pyroptosis and inhibited histone release induced by LPS. In vivo, LPS treatment in rats promoted caspase-1 immunoreactivity in astrocytes and caused an increase in the release of pro-inflammatory cytokines of IL-1β and IL-18, resulting in neuronal injury, which was attenuated by dexmedetomidine; this neuroprotective effect was abolished by α2-adrenoceptor antagonist atipamezole. Dexmedetomidine significantly reduced the high mortality rate caused by LPS challenge. Our data demonstrated that dexmedetomidine may protect glia cells via reducing pyroptosis and subsequently protect neurons, all of which may preserve brain function and ultimately improve the outcome in sepsis.

Journal article

Li T, Chen L, Zhao H, Wu L, Masters J, Han C, Hirota K, Ma Det al., 2019, Both Bupivacaine and Levobupivacaine inhibit colon cancer cell growth but not melanoma cells in vitro, Journal of Anesthesia, Vol: 33, Pages: 17-25, ISSN: 0913-8668

BackgroundRetrospective studies indicate that the use of regional anaesthesia causes a reduction in cancer recurrence after oncological surgery, which could be due to anaesthetic’s negating effect on immunosuppression related to the surgical stress response. Local anaesthetics may also exert direct suppressive effects on malignant cells, an area where further investigation is urgently needed.MethodsHuman colon cancer cells and human melanoma cells were cultured and then treated with 1 mM bupivacaine or levobupivacaine for up to 24 or 48 h. Their migratory ability was measured by scratch assay, proliferation determined with Ki67 immunofluorescence staining, and apoptosis accessed with annexin V and PI staining on flow cytometry. The effects of bupivacaine and levobupivacaine on cellular signaling and molecular response, specifically, on endoplasmic reticulum stress (ERS), were studied with immunostaining and western blot.ResultsIn colon cancer cells, treatment with bupivacaine and levobupivacaine significantly inhibited cell migration (**p < 0.01, ***p < 0.001; n = 4) and proliferation (**p < 0.01; n = 4), while increasing the expression of CHOP (***p < 0.001; n = 4) and decreased the expression of Grp78 (*p < 0.05; n = 4). These effects were not mirrored by melanoma cells, such that no significant increase in apoptosis was seen in either melanoma cell lines following treatment.ConclusionThese in vitro data suggested that both bupivacaine and levobupivacaine suppress colorectal adenocarcinoma cell proliferation and migration, which are concurrent with increased endoplasmic reticulum stress. Conversely, melanoma cells are more resilient to these two commonly used local anaesthetics. Further in vivo studies or clinical trials are needed.

Journal article

Singh M, Nabavi E, Zhou Y, Gallina ME, Zhao H, Ruenraroengsak P, Porter AE, Ma D, Cass AEG, Hanna GB, Elson DSet 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.

Journal article

Ning J, Zhao H, Chen B, Mi EZ, Yang Z, Qing W, Lam KWJ, Yi B, Chen Q, Gu J, Ichim T, Bogin V, Lu K, Ma Det 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

Journal article

Wang C, Datoo T, Zhao H, Wu L, Date A, Jiang C, Sanders RD, Wang G, Bevan C, Ma Det 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

Journal article

Ma J, Chen Q, Li J, Zhao H, Mi E, Chen Y, Yi B, Ning J, Ma D, Lu K, Gu Jet 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.

Journal article

Zhao H, Ma D, Huang H, Alam A, Chen Q, Suen KC, Cui J, Sun Q, Ologunde R, Zhang W, Lian Qet 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.

Journal article

Sun Y, Zhao H, Wang D, Ma Det al., 2018, Dexmedetomidine alleviates LPS-induced pyroptosis in astrocytes in vitro, BJA Research Forum, Publisher: ELSEVIER SCI LTD, Pages: E8-E9, ISSN: 0007-0912

Conference paper

Zhao H, Chen Q, Alam A, Cui J, Suen KC, Soo AP, Eguchi S, Gu J, Ma Det 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.

Journal article

Zhao H, Alam A, Pac Soo A, George AJT, Ma Det 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.

Journal article

Ciechanowicz S, Zhao H, Chen Q, Cui J, Mi E, Mi E, Lian Q, Ma Det al., 2018, Differential effects of sevoflurane on the metastatic potential and chemosensitivity of non-small-cell lung adenocarcinoma and renal cell carcinoma in vitro, BRITISH JOURNAL OF ANAESTHESIA, Vol: 120, Pages: 368-375, ISSN: 0007-0912

Journal article

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