120 results found
Iwasaki M, Zhao H, Hu C, et al., 2023, The differential cancer growth associated with anaesthetics in a cancer xenograft model of mice: mechanisms and implications of postoperative cancer recurrence, CELL BIOLOGY AND TOXICOLOGY, Vol: 39, Pages: 1561-1575, ISSN: 0742-2091
Chang E, Wang Y, Zhu R, et al., 2023, General anesthetic action profile on the human prefrontal cortex cells through comprehensive single-cell RNA-seq analysis, iScience, Vol: 26, Pages: 1-19, ISSN: 2589-0042
The cellular and molecular actions of general anesthetics to induce anesthesia state and also cellular signaling changes for subsequent potential "long term" effects remain largely elusive. General anesthetics were reported to act on voltage-gated ion channels and ligand-gated ion channels. Here we used single-cell RNA-sequencing complemented with whole-cell patch clamp and calcium transient techniques to examine the gene transcriptome and ion channels profiling of sevoflurane and propofol, both commonly used clinically, on the human fetal prefrontal cortex (PFC) mixed cell cultures. Both propofol and sevoflurane at clinically relevant dose/concentration promoted "microgliosis" but only sevoflurane decreased microglia transcriptional similarity. Propofol and sevoflurane each extensively but transiently (<2 h) altered transcriptome profiling across microglia, excitatory neurons, interneurons, astrocytes and oligodendrocyte progenitor cells. Utilizing scRNA-seq as a robust and high-through put tool, our work may provide a comprehensive blueprint for future mechanistic studies of general anesthetics in clinically relevant settings.
Li X, Chang E, Cui J, et al., 2023, Bv8 mediates myeloid cell migration and enhances malignancy of colorectal cancer, Frontiers in Immunology, Vol: 14, Pages: 1-13, ISSN: 1664-3224
Colorectal cancer (CRC) is the third most predominant malignancy in the world. Although the importance of immune system in cancer development has been well established, the underlying mechanisms remain to be investigated further. Here we studied a novel protein prokineticin 2 (Prok2, also known as Bv8) as a key pro-tumoral factor in CRC progression in in vitro and ex vivo settings. Human colorectal tumor tissues, myeloid cell lines (U937 cells and HL60 cells) and colorectal cancer cell line (Caco-2 cells) were used for various studies. Myeloid cell infiltration (especially neutrophils) and Bv8 accumulation were detected in human colorectal tumor tissue with immunostaining. The chemotactic effects of Bv8 on myeloid cells were presented in the transwell assay and chemotaxis assy. Cultured CRC cells treated with myeloid cells or Bv8 produced reactive oxygen species (ROS) and vascular endothelial growth factor (VEGF). Furthermore, ROS and VEGF acted as pro-angiogenesis buffer in myeloid cell-infiltrated CRC microenvironment. Moreover, myeloid cells or Bv8 enhanced energy consumption of glycolysis ATP and mitochondria ATP of CRC cells. Interestingly, myeloid cells increased CRC cell viability, but CRC cells decreased the viability of myeloid cells. ERK signalling pathway in CRC cells was activated in the presence of Bv8 or co-cultured myeloid cells. In conclusion, our data indicated the vital roles of Bv8 in myeloid cell infiltration and CRC development, suggesting that Bv8 may be a potential therapeutic target for colorectal cancer-related immunotherapy.
Chen Q, Liu X, Liu Z, et al., 2023, Tackling regulated cell death yields enhanced protection in lung grafts., Theranostics, Vol: 13, Pages: 4376-4390
Background: Effective preservation strategies to ameliorate lung graft ischaemia injury are needed to rescue 'extended criteria' or 'marginal' lung grafts, and to improve recipient outcomes after transplantation. Methods: Lung grafts from male Lewis rats were extracted after 40 min of cardiocirculatory death, and healthy human lung tissues were collected from patients undergoing a lobectomy. Lung samples were then preserved in a 4°C preservation solution supplemented with 0.1 nM Dexmedetomidine (Dex, α2-adrenoceptor agonist) for 16 h. In vitro, human lung epithelial A549 cells were preserved in the 4°C preservation solution with 0.1 nM Dex for 24 h, then re-cultured in the cell culture medium at 37°C to mimic the clinical scenario of cold ischaemia and warm reperfusion. Lung tissues and cells were then analysed with various techniques including western blot, immunostaining and electron microscope, to determine injuries and the protection of Dex. Results: Prolonged warm ischaemia after cardiocirculatory death initiated Rip kinase-mediated necroptosis, which was exacerbated by cold storage insult and enhanced lung graft injury. Dex supplementation significantly reduced necroptosis through upregulating Nrf2 activation and reducing oxidative stress, thereby significantly improving lung graft morphology. Dex treatment also attenuated endoplasmic reticulum stress, stabilised lysosomes and promoted cell membrane resealing function, consequently reducing cell death and inflammatory activation after hypothermic hypoxia-reoxygenation in A549 cells. Conclusions: Inhibition of regulated cell death through Dex supplementation to the graft preservation solution improves allograft quality which may aid to expand the donor lung pool and enhance lung transplant outcomes per se.
Huang H, Liu P, Zhang H, et al., 2022, Corrigendum to Triiodothyronine attenuates neurocognitive dysfunction induced by sevoflurane in the developing brain of neonatal rats [J Affect Disord. 2021 Oct 26; S0165-0327(21)01154-X.]., J Affect Disord, Vol: 298
Huang H, Liu P, Ma D, et 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
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.
Liu L, Sun Q, Davis F, et al., 2022, Epithelial-mesenchymal transition in organ fibrosis development: current understanding and treatment strategies, BURNS & TRAUMA, Vol: 10, ISSN: 2321-3868
Jiang C, Gonzalez-Anton S, Li X, et al., 2022, General anaesthetics reduce acute lymphoblastic leukaemia cell migration and homing in vitro and in vivo via CXCR4 and osteopontin mediated mechanisms, F1000Research, Vol: 11, ISSN: 2046-1402
Background: Acute lymphoblastic leukaemia (ALL) is the most common type of cancer in children. General anaesthetics are often used on patients undergoing painful procedures during ALL treatments but their effects on ALL malignancy remain unknown. Herein, we aim to study the effect of two commonly used general anaesthetics, intravenous propofol and inhalational sevoflurane, on the migration and homing of ALL cells in vitro and in vivo. Methods: NALM-6 cells were treated with propofol (5 and 10 μg/ml) or sevoflurane (3.6%) in vitro for six hours. Then, cells were harvested for flow cytometry analysis. For in vitro migration experiments, NALM-6 cells were pre-treated with propofol and sevoflurane for six hours before being loaded onto the upper chamber of a migration chamber and cells were collected in the lower chamber after six hours of migration. For in vivo adhesion assays, NALM-6 cells were pre-treated with propofol and sevoflurane before an adhesion assay was carried out. In in vitro experiments, GFP-NALM-6 cells were pre-treated with propofol (10 μg/ml) or sevoflurane (3.6%) for six hours. Then, cells were injected intravenously to C57BL/6 female mice followed by intravital microscopy. Results: Both anaesthetics reduced in vitro migration, in vivo migration and in vivo homing as exemplified by 1) the reduction in the number of cells entering the bone marrow and 2) the disturbance in homing location in relation to the nearest endosteal surface. Our results indicated that general anaesthetics reduced the surface CXCR4 expression. In addition, the adhesion of leukaemia cells to thrombin cleaved osteopontin (OPN) was reduced by general anaesthetics. Those changes might result in the alterations in migration and homing. Conclusion: Together, our data suggest that both propofol and sevoflurane could reduce ALL migration and homing in vivo and in vitro via CXCR4 and OPN mediated mechanisms.
Liao Z, Ou X, Zhou C, et al., 2022, Xenon attenuated neonatal lipopolysaccharide exposure induced neuronal necroptosis and subsequently improved cognition in juvenile rats., Front Pharmacol, Vol: 13, ISSN: 1663-9812
Background: Neonatal sepsis is known to cause neurodevelopment impairment and has been reported to increase risks for neurological/psychiatric disorders. In this study, we investigated the effect of xenon, a well-known potent neuroprotective gas, on neonatal sepsis-induced neurodevelopment impairment in rats together with underlying mechanism by focusing on receptor-interacting protein kinase (RIP) mediated neuronal necroptosis. Methods: 3-day-old Sprague-Dawley rat pups were exposed to either 70% xenon or N2 balanced with O2 for 6 h, during which lipopolysaccharide (LPS) was injected intraperitoneally for 3 times (500 μg/kg for the 1st and 250 μg/kg for the second and third dose; n = 6-10/group). In another cohort of 3-day-old rat pups, intracerebroventricular injection of necrostatin-1 (4 µg in 4 µl saline, a RIP-1-targeted inhibitor of necroptosis) was performed 20 min after the third dose of LPS. The learning ability and memory were assessed 25 days after LPS injection. Then, their hippocampus was collected for neuronal necroptosis with RIP and MIKL assessments using western blot and in situ immunostaining. Systemic and neuro-inflammation was also assessed. Results: LPS insult resulted in elevation of pro-inflammatory cytokine TNF-𝝰 and IL-6, caused neuronal necroptosis and damaged synaptic integrity at the brain developing stage, which finally led to the long-term cognitive impairment. Xenon inhibited necroptosis associated mediator RIP-1, RIP-3, and MLKL activation, protected neurons and attenuated cognitive dysfunction induced by LPS. Like xenon, the similar pattern changes induced by a RIP-1 inhibitor Necrostatin-1 were also found. Conclusion: This study indicates that necroptosis is involved in neonatal sepsis-induced neurofunctional impairments and xenon may be a novel therapeutic strategy to prevent/treat cognitive impairment in neonatal septic patients.
Chen Q, Qin Z, Sun Y, et 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
Hu C, Huang Y, Wu L, et al., 2021, 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
Chen L, Alam A, Pac-Soo A, et al., 2021, Pretreatment with valproic acid alleviates pulmonary fibrosis through epithelial-mesenchymal transition inhibition in vitro and in vivo., Lab Invest, Vol: 101, Pages: 1166-1175
Epithelial-mesenchymal transition (EMT) plays a crucial role in the development of pulmonary fibrosis. This study aims to investigate the effects of valproic acid (VPA) on EMT in vitro and in vivo. In vitro, EMT was induced by the administration of transforming growth factor-β1 (TGF-β1) in a human alveolar epithelial cell line (A549). The dose effects of VPA (0.1-3 mM) on EMT were subsequently evaluated at different timepoints. VPA (1 mM) was applied prior to the administration of TGF-β1 and the expression of E-cadherin, vimentin, p-Smad2/3 and p-Akt was assessed. In addition, the effects of a TGF-β type I receptor inhibitor (A8301) and PI3K-Akt inhibitor (LY294002) on EMT were evaluated. In vivo, the effects of VPA on bleomycin-induced lung fibrosis were evaluated by assessing variables such as survival rate, body weight and histopathological changes, whilst the expression of E-cadherin and vimentin in lung tissue was also evaluated. A8301 and LY294002 were used to ascertain the cellular signaling pathways involved in this model. The administration of VPA prior to TGF-β1 in A549 cells prevented EMT in both a time- and concentration-dependent manner. Pretreatment with VPA downregulated the expression of both p-Smad2/3 and p-Akt. A8301 administration increased the expression of E-cadherin and reduced the expression of vimentin. LY294002 inhibited Akt phosphorylation induced by TGF-β1 but failed to prevent EMT. Pretreatment with VPA both increased the survival rate and prevented the loss of body weight in mice with pulmonary fibrosis. Interestingly, both VPA and A8301 prevented EMT and facilitated an improvement in lung structure. Overall, pretreatment with VPA attenuated the development of pulmonary fibrosis by inhibiting EMT in mice, which was associated with Smad2/3 deactivation but without Akt cellular signal involvement. This study investigated the effect of valproic acid (VPA) on epithelial-mesenchymal transition (EMT). In vitro, VP
Chen L, Alam A, Pac-Soo A, et 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
Ishikawa M, Iwasaki M, Zhao H, et al., 2021, Inhalational Anesthetics Inhibit Neuroglioma Cell Proliferation and Migration via miR-138,-210 and-335, INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, Vol: 22
Ishikawa M, Iwasaki M, Zhao H, et 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, ISSN: 1661-6596
Iwasaki M, Saito J, Zhao H, et al., 2021, 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
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
Zhen C, Zhao H, Wu L, et al., 2020, The Role of Neutrophil NETosis in Organ Injury: Novel Inflammatory Cell Death Mechanisms, INFLAMMATION, Vol: 43, Pages: 2021-2032, ISSN: 0360-3997
Yang S-R, Hua K-F, Chu LJ, et al., 2020, Xenon blunts NF-κB/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
Zhang W, Sheng B, Chen S, et al., 2020, Sevoflurane Enhances Proliferation, Metastatic Potential of Cervical Cancer Cells <i>via</i> the Histone Deacetylase 6 Modulation <i>In Vitro</i>, ANESTHESIOLOGY, Vol: 132, Pages: 1469-1481, ISSN: 0003-3022
Hu C, Liu Z, Zhao H, et 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.
Zhao H, Chen Q, Huang H, et 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
Duan J, Yang Z, Huang J, et 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
Wu L, Zhao H, Weng H, et 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
Chen L, Zhao H, Alam A, et al., 2019, Postoperative remote lung injury and its impact on surgical outcome, BMC ANESTHESIOLOGY, Vol: 19, ISSN: 1471-2253
Sun Y-B, Zhao H, Mu D-L, et 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.
Li T, Chen L, Zhao H, et 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.
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.
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