scholarly journals Integration Strategy of ROS Boosting and Antioxidation Inhibiting Initiates Ferroptosis to Enhance Phototherapic Effect on Tumor

2021 ◽  
Author(s):  
Weiwei Tao ◽  
Neng Wang ◽  
Jie Ruan ◽  
Yue Hu ◽  
Chao Wang ◽  
...  
Keyword(s):  
Great Promise ◽  
Ros Generation ◽  
Therapeutic Effects ◽  
Integration Strategy ◽  
Oxygen Generator ◽  
Synergistic Modulation ◽  
High Level ◽  
Shock Proteins

Abstract Conventional phototherapy is often limited by hypoxia, introducing oxygen generators is the common method to relieve it, but the antioxidant path of tumor cell was inevitably initiated. Herein, by integrating oxygen generator (MnO2) and inhibitor of Nrf2 (brusatol) into one nanoplatform, we strive to relieve hypoxia and inhibit the antioxidation simultaneously. Hypoxia was relieved for the triggered decomposition of MnO2 by endogenous H2O2 and it directly strengthened photodynamic therapy (PDT) through boosting reactive oxygen species (ROS) generation. Moreover, high level ROS greatly enhanced the efficacy of photothermal therapy (PTT) by attacking heat shock proteins(HSP). Antioxidant defense was prevented by brusatol through inhibiting the expression of Nrf2. Importantly, MnO2 and brusatol collaboratively induced ferroptosis through raising oxidation, remarkably promoting tumor curative effect. Both in vitro and in vivo experiments demonstrated the strengthened therapeutic effects of synergistic PDT/PTT, highlighting the great promise of the synergistic modulation strategy with a nanomedicine to overcome the drawbacks of phototherapy.

Protective Effect of Schisandrin B Against Cyclosporine A-Induced Nephrotoxicity In Vitro and In Vivo

2012 ◽  
Vol 40 (03) ◽  
pp. 551-566 ◽  
Author(s):  
Shaohua Zhu ◽  
Yan Wang ◽  
Meiwan Chen ◽  
Jing Jin ◽  
Yuwen Qiu ◽  
...  
Keyword(s):  
Cell Viability ◽  
Cyclosporine A ◽  
Tubular Epithelial Cell ◽  
Epithelial Cell Line ◽  
Ros Generation ◽  
Therapeutic Effects ◽  
Schisandrin B ◽  
Protective Effects

Schisandrin B (Sch B) is an active ingredient of the fruit of Schisandra chinensis. It has many therapeutic effects arising from its tonic, sedative, antitussive and antiaging activities and is also used in the treatment of viral and chemical hepatitis. The aim of this study was to investigate the protective effects of Sch B on cyclosporine A (CsA)-induced nephrotoxicity in mice and HK-2 cells (a human proximal tubular epithelial cell line). After gavage with Sch B (20 mg/kg) or olive oil (vehicle), mice received CsA (30 mg/kg) by subcutaneous injection once daily for four weeks. Renal function, histopathology, and tissue glutathione (GSH) and malondialdehyde (MDA) levels were evaluated after the last treatment. The effects of Sch B on CsA–induced oxidative damage in HK-2 cells were investigated by measuring cell viability, the release of lactate dehydrogenase (LDH), the level of reactive oxygen species (ROS), and the cellular GSH and ATP concentrations. Cellular apoptosis was assessed by flow cytometry. Treatment with Sch B in CsA-treated mice significantly suppressed the elevation of blood urea nitrogen (BUN) and serum creatinine levels and attenuated the histopathological changes. Additionally, Sch B also decreased renal MDA levels and increased GSH levels in CsA-treated mice. Using an in vitro model, Sch B (2.5, 5 and 10 μM) significantly increased the cell viability and reduced LDH release and apoptosis induced by CsA (10 μM) in HK-2 cells. Furthermore, Sch B increased the intracellular GSH and ATP levels and attenuated CsA-induced ROS generation. In conclusion, Sch B appears to protect against CsA-induced nephrotoxicity by decreasing oxidative stress and cell death.

scholarly journals Erythropoietin as a Neuroprotective Molecule: An Overview of Its Therapeutic Potential in Neurodegenerative Diseases

ASN NEURO ◽  
2019 ◽  
Vol 11 ◽  
pp. 175909141987142 ◽  
Author(s):  
Federica Rey ◽  
Alice Balsari ◽  
Toniella Giallongo ◽  
Sara Ottolenghi ◽  
Anna M. Di Giulio ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Therapeutic Potential ◽  
Erythropoietin Receptor ◽  
Great Promise ◽  
Therapeutic Effects ◽  
Erythroid Progenitor ◽  
Beneficial Effects ◽  
Cord Injury

Erythropoietin (EPO) is a cytokine mainly induced in hypoxia conditions. Its major production site is the kidney. EPO primarily acts on the erythroid progenitor cells in the bone marrow. More and more studies are highlighting its secondary functions, with a crucial focus on its role in the central nervous system. Here, EPO may interact with up to four distinct isoforms of its receptor (erythropoietin receptor [EPOR]), activating different signaling cascades with roles in neuroprotection and neurogenesis. Indeed, the EPO/EPOR axis has been widely studied in the neurodegenerative diseases field. Its potential therapeutic effects have been evaluated in multiple disorders, such as Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, spinal cord injury, as well as brain ischemia, hypoxia, and hyperoxia. EPO is showing great promise by counteracting secondary neuroinflammatory processes, reactive oxygen species imbalance, and cell death in these diseases. Multiple studies have been performed both in vitro and in vivo, characterizing the mechanisms through which EPO exerts its neurotrophic action. In some cases, clinical trials involving EPO have been performed, highlighting its therapeutic potential. Together, all these works indicate the potential beneficial effects of EPO.

scholarly journals Gardenoside Hinders Caspase-1-Mediated Hepatocyte Pyroptosis Through the CTCF/DPP4 Signaling Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Tian Shen ◽  
Tao Lei ◽  
Lin Chen ◽  
Bing-Bing Zhu ◽  
Bi-Lin Xu ◽  
...  
Keyword(s):  
Cell Death ◽  
Lipid Accumulation ◽  
Luciferase Reporter ◽  
Ros Generation ◽  
Inflammasome Activation ◽  
Therapeutic Effects ◽  
Alcoholic Fatty Liver ◽  
Caspase 1

Non-alcoholic fatty liver disease (NAFLD)is accompanied by typical inflammatory damage and cell death. As a pro-inflammatory form of cell death, pyroptosis participates in important pathological processes involved in NAFLD. Regulatory roles of both CCCTC-binding factor (CTCF) and dipeptidyl peptidase-4 (DPP4) have been reported in NAFLD, but it is still unclear whether the mechanism of action of gardenoside, a potential therapeutic for NAFLD, can be driven via these proteins. In this study, the direct interaction between CTCF and DPP4 was first confirmed by a dual-luciferase reporter assay system. Then, a cell model of NAFLD was established by induction with palmitic acid (PA) and lipopolysaccharide (LPS). A mouse NAFLD model was established, and the effect of gardenoside on both the cell and mouse models of NAFLD was also investigated. Increased lipid accumulation, NLRP3 inflammasome activation, and hepatocyte pyroptosis were recorded in NAFLD in vitro and in vivo. Gardenoside treatment effectively reduced the lipid accumulation, increased cell viability, reduced reactive oxygen species (ROS) generation, and attenuated pyroptosis and apoptosis in NAFLD in the in vitro and in vivo models. Alterations in these biological processes were evidenced by the decreased expression levels of several pro-pyroptotic markers including the NLR family, pyrin domain-containing 3 (NLRP3), apoptosis-related speckle-like protein (ASC), caspase-1 p20, Gasdermin D N-terminal domain (GSDMD-N), and IL-1β, along with simultaneously decreased CTCF and DPP4 levels. Importantly, CTCF silencing or DPP4 silencing exhibited effects similar to gardenoside treatment, while CTCF overexpression counteracted this trend, which indicated that CTCF might be a target responsible for gardenoside-induced alleviation of NAFLD, such therapeutic effects might be achieved through controlling the expression of the direct target of CTCF (DPP4) and several downstream molecules. In general, the current study provides a promising strategy for NAFLD treatment.

scholarly journals Therapeutic Effects of Human Urine-Derived Stem Cells in a Rat Model of Cisplatin-Induced Acute Kidney Injury In Vivo and In Vitro

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Bishao Sun ◽  
Xing Luo ◽  
Chengfei Yang ◽  
Peilin Liu ◽  
Yang Yang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Acute Kidney Injury ◽  
Rat Model ◽  
Kidney Injury ◽  
Ultrastructural Changes ◽  
Great Promise ◽  
Therapeutic Effects ◽  
Differentiation Potential

Acute kidney injury (AKI) is an extremely dangerous clinical syndrome with high morbidity and mortality. Stem cell-based therapies have shown great promise for AKI treatment. Urine-derived stem cells (USCs) are a novel cell source in tissue engineering and cell therapy which provide advantages of simple, noninvasive, and low-cost harvest methods, efficient proliferation, and multi-differentiation potential. Here, we described the therapeutic effects of USCs in a rat model of cisplatin-induced AKI as a novel therapy. In vivo, the intravenous administration of USCs alleviated the renal functional damage in AKI rats, for the levels of blood urea nitrogen (BUN) and serum creatinine (SCr) were significantly decreased. The USCs-treated group also exhibited improved histological and ultrastructural changes, promoted proliferation, and inhibited apoptosis in renal tissues. After the USC therapy, the expression levels of proinflammatory cytokines (TNF-α and IL-6) and apoptosis-related proteins (BAX and cleaved caspase-3) were downregulated. In addition, the presence of a few GFP-labeled USCs was confirmed in rat renal tissues. In vitro, rat tubular epithelial (NRK-52E) cells were incubated with cisplatin to induce cell damage and then cocultured with USCs. After coculture with USCs, the cisplatin-induced NRK-52E cells showed higher cell viability and a lower apoptosis ratio than those of the control group, and cell cycle arrest was improved. In conclusion, our results demonstrated that USC therapy significantly improved the renal function and histological damage, inhibited the inflammation and apoptosis processes in the kidney, and promoted tubular epithelial proliferation. Our study exhibited the potential of USCs in the treatment of AKI, representing a new clinical therapeutic strategy.

scholarly journals Andrographolide Attenuates Established Pulmonary Hypertension via Rescue of Vascular Remodeling

Biomolecules ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1801
Author(s):  
Chenyou Shen ◽  
Jianxin Tan ◽  
Xusheng Yang ◽  
Wei Wang ◽  
Youai Dai ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Vascular Remodeling ◽  
Chronic Hypoxia ◽  
Pulmonary Arteries ◽  
Mapk Signaling ◽  
Ros Generation ◽  
Therapeutic Effects ◽  
Related Factor

Pulmonary hypertension (PH) is characterized by vascular remodeling caused by marked proliferation of pulmonary artery smooth muscle cells (PASMCs). Andrographolide (ANDRO) is a potent anti-inflammatory agent which possesses antioxidant, and has anticarcinogenic activity. The present study examined potential therapeutic effects of ANDRO on PH in both chronic hypoxia and Sugen5416/hypoxia mouse PH models. Effects of ANDRO were also studied in cultured human PASMCs isolated from either healthy donors or PH patients. In vivo, ANDRO decreased distal pulmonary arteries (PAs) remodeling, mean PA pressure and right ventricular hypertrophy in chronic hypoxia- and Sugen/hypoxia-induced PH in mice. ANDRO reduced cell viability, proliferation and migration, but increased cell apoptosis in the PASMCs isolated from PH patients. ANDRO also reversed the dysfunctional bone morphogenetic protein receptor type-2 (BMPR2) signaling, suppressed [Ca2+]i elevation, reactive oxygen species (ROS) generation, and the upregulated expression of IL-6 and IL-8, ET-1 and VEGF in PASMCs from PH patients. Moreover, ANDRO significantly attenuated the activation of TLR4/NF-κB, ERK- and JNK-MAPK signaling pathways and reversed the inhibition of p38-MAPK in PASMCs of PH patients. Further, ANDRO blocked hypoxia-triggered ROS generation by suppressing NADPH oxidase (NOX) activation and augmenting nuclear factor erythroid 2-related factor 2 (Nrf2) expression both in vitro and in vivo. Conventional pulmonary vasodilators have limited efficacy for the treatment of severe PH. We demonstrated that ANDRO may reverse pulmonary vascular remodeling through modulation of NOX/Nrf2-mediated oxidative stress and NF-κB-mediated inflammation. Our findings suggest that ANDRO may have therapeutic value in the treatment of PH.

Clinical Trials in Thrombosis: Secondary Prevention of Myocardial Infarction

1976 ◽  
Vol 35 (01) ◽  
pp. 049-056 ◽  
Author(s):  
Christian R Klimt ◽  
P. H Doub ◽  
Nancy H Doub
Keyword(s):  
Myocardial Infarction ◽  
Secondary Prevention ◽  
Case Control ◽  
Therapeutic Effects ◽  
Case Control Studies ◽  
Definitive Answer ◽  
Inhibition Of Platelet Aggregation ◽  
Prospective Trials

SummaryNumerous in vivo and in vitro experiments, investigating the inhibition of platelet aggregation and the prevention of experimentally-induced thrombosis, suggest that anti-platelet drugs, such as aspirin or the combination of aspirin and dipyridamole or sulfinpyrazone, may be effective anti-thrombotic agents in man. Since 1971, seven randomized prospective trials and two case-control studies have been referenced in the literature or are currently being conducted, which evaluate the effects of aspirin, sulfinpyrazone, or dipyridamole in combination with aspirin in the secondary prevention of myocardial infarction. A critical review of these trials indicates a range of evidence from no difference to a favorable trend that antiplatelet drugs may serve as anti-thrombotic agents in man. To date, a definitive answer concerning the therapeutic effects of these drugs in the secondary prevention of coronary heart disease is not available.

scholarly journals Aberrantly high activation of a FoxM1–STMN1 axis contributes to progression and tumorigenesis in FoxM1-driven cancers

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Jun Liu ◽  
Jipeng Li ◽  
Ke Wang ◽  
Haiming Liu ◽  
Jianyong Sun ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Poor Prognosis ◽  
Soft Agar ◽  
Transcriptional Level ◽  
Regulation Mechanism ◽  
Strong Positive Correlation ◽  
Cell Viability Assay ◽  
High Level

AbstractFork-head box protein M1 (FoxM1) is a transcriptional factor which plays critical roles in cancer development and progression. However, the general regulatory mechanism of FoxM1 is still limited. STMN1 is a microtubule-binding protein which can inhibit the assembly of microtubule dimer or promote depolymerization of microtubules. It was reported as a major responsive factor of paclitaxel resistance for clinical chemotherapy of tumor patients. But the function of abnormally high level of STMN1 and its regulation mechanism in cancer cells remain unclear. In this study, we used public database and tissue microarrays to analyze the expression pattern of FoxM1 and STMN1 and found a strong positive correlation between FoxM1 and STMN1 in multiple types of cancer. Lentivirus-mediated FoxM1/STMN1-knockdown cell lines were established to study the function of FoxM1/STMN1 by performing cell viability assay, plate clone formation assay, soft agar assay in vitro and xenograft mouse model in vivo. Our results showed that FoxM1 promotes cell proliferation by upregulating STMN1. Further ChIP assay showed that FoxM1 upregulates STMN1 in a transcriptional level. Prognostic analysis showed that a high level of FoxM1 and STMN1 is related to poor prognosis in solid tumors. Moreover, a high co-expression of FoxM1 and STMN1 has a more significant correlation with poor prognosis. Our findings suggest that a general FoxM1-STMN1 axis contributes to cell proliferation and tumorigenesis in hepatocellular carcinoma, gastric cancer and colorectal cancer. The combination of FoxM1 and STMN1 can be a more precise biomarker for prognostic prediction.

scholarly journals Therapeutic effects of sesamolin on leukemia induced by WEHI-3B in model mice

2021 ◽  
Vol 64 (1) ◽  
Author(s):  
Senthil Nagarajan ◽  
Jae Kwon Lee
Keyword(s):  
Nk Cell ◽  
Neoplastic Cell ◽  
Positive Control ◽  
Cytolytic Activity ◽  
Leukemic Cells ◽  
Therapeutic Effects ◽  
Control Drug ◽  
Lysis Activity

AbstractSesamolin is one of the lignans derived from sesame oil. It has demonstrated significant antioxidant, anti-aging, and anti-mutagenic properties. It also reportedly augments natural killer (NK) cell lysis activity. We previously reported that sesamolin also exerts anticancer effects in vitro and induces enhanced NK cell cytolytic activity against tumor cells. Herein, we aimed to determine the mechanism by which sesamolin prevents and retards tumorigenesis in BALB/c mouse models of leukemia induced by murine (BALB/c) myelomonocytic leukemia WEHI-3B cells. Banded neutrophils, myeloblasts, and monocytic leukemic cells were more abundant in the leukemia model than in normal mice. Sesamolin decreased the number of leukemic cells by almost 60% in the leukemia model mice in vivo; additionally, sesamolin and the positive control drug, vinblastine, similarly hindered neoplastic cell proliferation. Spleen samples were ~ 4.5-fold heavier in leukemic mice than those obtained from normal mice, whereas spleen samples obtained from leukemic mice treated with sesamolin had a similar weight to those of normal mice. Moreover, sesamolin induced a twofold increase in the cytotoxic activity of leukemic mouse NK cells against WEHI-3B cells. These results indicated that sesamolin exerts anti-leukemic effects in vivo.

scholarly journals High-throughput screening and rational design of biofunctionalized surfaces with optimized biocompatibility and antimicrobial activity

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Zhou Fang ◽  
Junjian Chen ◽  
Ye Zhu ◽  
Guansong Hu ◽  
Haoqian Xin ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
High Throughput ◽  
High Throughput Screening ◽  
Rational Design ◽  
Click Reaction ◽  
Reaction Times ◽  
Great Promise ◽  
Biomaterial Surfaces

AbstractPeptides are widely used for surface modification to develop improved implants, such as cell adhesion RGD peptide and antimicrobial peptide (AMP). However, it is a daunting challenge to identify an optimized condition with the two peptides showing their intended activities and the parameters for reaching such a condition. Herein, we develop a high-throughput strategy, preparing titanium (Ti) surfaces with a gradient in peptide density by click reaction as a platform, to screen the positions with desired functions. Such positions are corresponding to optimized molecular parameters (peptide densities/ratios) and associated preparation parameters (reaction times/reactant concentrations). These parameters are then extracted to prepare nongradient mono- and dual-peptide functionalized Ti surfaces with desired biocompatibility or/and antimicrobial activity in vitro and in vivo. We also demonstrate this strategy could be extended to other materials. Here, we show that the high-throughput versatile strategy holds great promise for rational design and preparation of functional biomaterial surfaces.

scholarly journals Fe3O4@Pt nanoparticles to enable combinational electrodynamic/chemodynamic therapy

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Tong Chen ◽  
Qiang Chu ◽  
Mengyang Li ◽  
Gaorong Han ◽  
Xiang Li
Keyword(s):  
Fenton Reaction ◽  
Pt Nanoparticles ◽  
Therapeutic Modality ◽  
Ros Generation ◽  
Tumor Treatment ◽  
Superior Efficacy ◽  
Platinum Nanocrystals ◽  
First Time

AbstractElectrodynamic therapy (EDT) has recently emerged as a potential external field responsive approach for tumor treatment. While it presents a number of clear superiorities, EDT inherits the intrinsic challenges of current reactive oxygen species (ROS) based therapeutic treatments owing to the complex tumor microenvironment, including glutathione (GSH) overexpression, acidity and others. Herein for the first time, iron oxide nanoparticles are decorated using platinum nanocrystals (Fe3O4@Pt NPs) to integrate the current EDT with chemodynamic phenomenon and GSH depletion. Fe3O4@Pt NPs can effectively induce ROS generation based on the catalytic reaction on the surface of Pt nanoparticles triggered by electric field (E), and meanwhile it may catalyze intracellular H2O2 into ROS via Fenton reaction. In addition, Fe3+ ions released from Fe3O4@Pt NPs under the acidic condition in tumor cells consume GSH in a rapid fashion, inhibiting ROS clearance to enhance its antitumor efficacy. As a result, considerable in vitro and in vivo tumor inhibition phenomena are observed. This study has demonstrated an alternative concept of combinational therapeutic modality with superior efficacy.

Sign in / Sign up

Export Citation Format

Share Document