CELLULAR PHYSIOLOGY AND BIOCHEMISTRY
·
2014
·Vol. 34
·期 5
·1780-1791
·
IF 3.55
Zhang Rong,Xiang Yang,Ran Qian,Deng Xiaojun,Xiao Yanni,Xiang Lixin,Li Zhongjun
Aim: The aim of this study was to investigate the mechanisms of Cr6+-induced red blood cells (RBCs) damage. Methods: The effect of Cr6+ exposure on RBCs was evaluated by hemolytic rate and blood gas assays. After exposure to 20 μM Cr6+, the percentage of phosphatidylserine (PS)-exposing cells, intracellular Ca2+, reactive oxygen species (ROS), and ATP levels were evaluated, and cell morphology was observed. RBCs were exposed to Cr6+ in different Ringer solutions to investigate the role of changes of Ca2+, ROS, and ATP levels in eryptosis and morphology. Results: The Cr6+-induced damage of RBCs was dose-dependent. After a 6 h incubation with Cr6+, RBCs exhibited significant Ca2+ influx, ROS increase, ATP depletion, and PS exposure, but displayed no obvious change in morphology at this time point. After 24 h Cr6+ exposure, the RBCs decreased in size, appeared to be spike-like, and had decreased forward scatter. Inhibition of Ca2+ influx attenuated PS-exposure caused by 6 h Cr6+ exposure, but did not prevent 24 h Cr6+ exposure-induced morphological change in RBCs. Inhibition of rapid ATP consumption using adenine significantly ameliorated Cr6+-caused PS-exposure at 12 h, 24 h and 48 h, and prevented 24 h Cr6+ incubation-induced morphological change in RBCs. Conclusion: Cr6+ can lead to eryptosis. Ca2+ influx, increased ROS levels, and rapid ATP consumption are closely related to Cr6+-induced RBCs damage. Ca2+ influx plays an extremely important role in Cr6+-mediated toxicity
研究领域:
毒理学
·
血液学
✓ 已验证
DOI
PubMed
高影响因子
STAR Protocols
·
2022
·
IF 0
Yanyan Ding,Feng Liu
Summary Understanding chromatin dynamics in red blood cells (RBCs) is critical for exploring the differentiation process and homeostasis maintenance during erythropoiesis. Here, we describe a protocol for isolation of zebrafish erythrocytes labelled with gata1 :dsRed by fluorescence-activated cell sorting. We detail steps for ATAC-seq library construction from the isolated RBCs and describe how to analyze the quality of the library. The library can then be used to assay genome-wide chromatin accessibility in these RBCs. For complete details on the use and execution of this protocol, please refer to Ding et al. (2021). 1
研究领域:
基因组学
·
分子生物学
·
血液学
✓ 已验证
DOI
PubMed
Genes
·
2023
·Vol. 14
·期 5
·1011
·
IF 3.5
Lei Yang,Sheng He,Ling Ling,Fangfang Wang,Lei Xu,Lei Fang,Fan Wu,Shuting Zhou,Fan Yang,Hongwei Wei,Duonan Yu
miR-144/451and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) regulate two antioxidative systems that have been identified to maintain redox homeostasis in erythroid cells by removing excess reactive oxygen species (ROS). Whether these two genes coordinate to affect ROS scavenging and the anemic phenotype, or which gene is more important for recovery from acute anemia, has not been explored. To address these questions, we crossedmiR-144/451knockout (KO) andNrf2KO mice and examined the phenotype change in the animals as well as the ROS levels in erythroid cells either at baseline or under stress condition. Several discoveries were made in this study. First,Nrf2/miR-144/451double-KO mice unexpectedly exhibit similar anemic phenotypes asmiR-144/451single-KO mice during stable erythropoiesis, although compound mutations ofmiR-144/451andNrf2lead to higher ROS levels in erythrocytes than single gene mutations. Second,Nrf2/miR-144/451double-mutant mice exhibit more dramatic reticulocytosis thanmiR-144/451orNrf2single-KO mice during days 3 to 7 after inducing acute hemolytic anemia using phenylhydrazine (PHZ), indicating a synergistic effect ofmiR-144/451and Nrf2 on PHZ-induced stress erythropoiesis. However, the coordination does not persist during the whole recovery stage of PHZ-induced anemia; instead,Nrf2/miR-144/451double-KO mice follow a recovery pattern similar tomiR-144/451single-KO mice during the remaining period of erythropoiesis. Third, the complete recovery from PHZ-induced acute anemia inmiR-144/451KO mice takes longer than inNrf2KO mice. Our findings demonstrate that complicated crosstalk betweenmiR-144/451and Nrf2 does exist and the crosstalk of these two antioxidant systems is development-stage-dependent. Our findings also demonstrate thatmiRNAdeficiency could result in a more profound defect of erythropoiesis than dysfunctional transcription factors.Keywords:miR-144/451;Nrf2;hemolytic anemia;reactive oxygen species
研究领域:
血液学
·
分子生物学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Jiacheng Wang,Yuhang Zhang,Yingbin Xu,Hongyu Jin,Can Yang,Hongxing Liu,Yongbo Bao
The blood clam ( Anadara granosa ) exhibits innovative red blood compared to other molluscs, with erythrocytes constituting 79 % to 89 % of the total hemocyte count. Previously, we identified that GATA-binding protein 1 (designated as Ag GATA1) was significantly up-regulated in the transcriptomes of blood clam populations with high hemocyte counts. However, the function of Ag GATA1 in erythropoiesis remains unknown. In this study, we conducted GATA1 knockdown experiments in A. granosa , which resulted in a significant reduction of both erythrocytes and other cells during the S phase, as well as significantly decreased proliferative activity in the gill tissue. The cell proliferation assay demonstrated that overexpression of Ag GATA1 increased the DNA replication activity of K562 cells. Additionally, o-dianisidine staining revealed defects in erythropoiesis within the gill tissue following Ag GATA1 knockdown, while protein analyses confirmed a significant reduction in Ag GATA1 expression. Furthermore, decreased cytoskeletal fluorescence and morphological changes in erythrocytes suggest that Ag GATA1 influenced cytoskeletal protein expression, leading to changes in erythrocyte morphology. This study provides new insights into the role of Ag GATA1 in hemocyte formation and highlights its significance in understanding erythropoiesis within invertebrate developmental tissues.
研究领域:
分子生物学
·
发育生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nutrients
·
2022
·Vol. 14
·期 3
·618
·
IF 6.706
Zhi Huang,Xing Liu,Ziming Li,Luwei Cui,Candi Liu,Weifeng Wang,Yuming Hu,Bo Chen
Background. Minerals play important biological roles in lipid metabolism. The primary aim of this study was to examine the relationships between erythrocyte fatty acids (FAs) levels with whole blood mineral elements concentrations among Chinese children. Methods. A cross-sectional study was conducted. A total of 435 children aged 4–7 years were recruited. Whole blood mineral elements were determined by atomic absorption spectrometry and erythrocyte FAs composition by gas chromatography-mass spectrometer. Results. There were direct correlations between Zn and C18:2n-6 (FDR correctedp= 0.019), total n-6 PUFAs (FDR correctedp= 0.034), and total PUFAs (FDR correctedp= 0.034). Direct correlations were found between whole blood Zn and C18:1n-9 (FDR correctedp= 0.035), C24:1n-9 (FDR correctedp= 0.023), total MUFAs (FDR correctedp= 0.023), and C18:2n-6 (FDR correctedp= 0.048) in the Cu < P50 group. In the Cu ≥ P50 group, Mg was inversely related to most FAs (All FDR correctedp< 0.05). In the Zn < P50 group, Cu was directly related to C24:1n-9, total MUFAs, C20:5n-3, C22:6n-3, total n-3 PUFAs, C20:4n-6, total n-6 PUFAs, total PUFAs, and total FAs (All FDR correctedp< 0.05). Conclusions. Whole blood Cu and Zn levels were directly linked to several FAs levels in the erythrocytes of children. The interactions of Mg, Cu, and Zn with fatty acids may affect FA metabolism, in which Mg influences FA absorption.Keywords:erythrocyte;mineral elements;fatty acids;children
研究领域:
营养学
·
生物化学
✓ 已验证
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2024
·
IF 5.4
Jia Zhou,Zhaohui Jiang,Runbin Sun,Di Pan,Qianming Du,Xiang Zhou,Yi Chen,Yan Chen,Jianqing Peng
Inspired by the "natural camouflage" strategy, cell-based biomimetic drug delivery systems (BDDS) have shown great potential in cancer therapy. Red blood cell (RBC) delivery vehicles and red blood cell membrane (RBCm)-camouflaged vehicles were commonly used strategies for drug delivery. We prepared shikonin-encapsulated PLGA nanoparticles (PLGA/SK) with different surface charges to obtain both RBC delivery and RBCm-camouflaged PLGA NPs. The physicochemical properties, in vivo circulation and antitumor effects of these biomimetic preparations were studied. Since the positive PLGA NPs may affect the morphology and function of RBCs, the biomimetic preparations prepared by the negative PLGA NPs showed better in vitro stability. However, positive PLGA NP-based biomimetic preparations exhibited longer circulation time and higher tumor region accumulation, leading to stronger anti-tumor effects. Meanwhile, the RBC delivery PLGA(+) NPs possessed better in vitro cytotoxicity, longer circulation time and higher tumor accumulation than RBCm-camouflaged PLGA(+) NPs. Collectively, RBC delivery vehicles possessed more potential than RBCm-camouflaged vehicles on drug delivery for tumor treatment, especially with positive NPs-loaded.
研究领域:
药学
·
纳米技术
·
癌症治疗
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
LIFE SCIENCES
·
2024
·
IF 5.2
Xuehan Dou,Zhongyuan Chen,Yunzhang Liu,Yun Li,Junli Ye,Ling Lu
Aims Prolyl hydroxylase domain 2 (PHD2), encoded by the Egln1 gene, serves as a pivotal regulator of the hypoxia-inducible factor (HIF) pathway and acts as a cellular oxygen sensor. Somatic inactivation of Phd2 in mice results in polycythemia and congestive heart failure. However, due to the embryonic lethality of Phd2 deficiency, its role in development remains elusive. Here, we investigated the function of two egln1 paralogous genes, egln1a and egln1b , in zebrafish. Main methods The egln1 null zebrafish were generated using the CRISPR/Cas9 system. Quantitative real-time PCR assays and Western blot analysis were employed to detect the effect of egln1 deficiency on the hypoxia signaling pathway. The hypoxia response of egln1 mutant zebrafish were assessed by analyzing heart rate, gill agitation frequency, and blood flow velocity. Subsequently, o-dianisidine staining and in situ hybridization were used to investigate the role of egln1 in zebrafish hematopoietic function. Key findings Our data show that the loss of egln1a or egln1b individually has no visible effects on growth rate. However, the egln1a ; egln1b double mutant displayed significant growth retardation and elevated mortality at around 2.5 months old. Both egln1a - null and egln1b - null zebrafish embryo exhibited enhanced tolerance to hypoxia, systemic hypoxic response that include hif pathway activation, increased cardiac activity, and polycythemia. Significance Our research introduces zebrafish egln1 mutants as the first congenital embryonic viable systemic vertebrate animal model for PHD2, providing novel insights into hypoxic signaling and the progression of PHD2- associated disease.
研究领域:
发育生物学
·
分子生物学
·
遗传学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2025
·
IF 11.5
Zhuge Deli,Li Li,Sun Xueying,Liang Hui,Jin Chenjie,Lu Ailing,Gao Wenli,Zhong Yutong,Li Wenlu,Chen Sihao,Wang Fang,Yan Linzhi,Meng Weiyang,Lin Xiaoji,Zhang Xufei,Liu Yong,Li Yuanfeng,Zhao Yingzheng,Zhang Xiang,Chen Mengchun,Chen Yijie
Phototherapy holds great potential for treating cancer and infections but faces limitations related to photosensitizer accumulation, tissue penetration, and diminished photo-conversion efficiency, particularly in deep-seated tumors and infections. Here, a biomimetic phototherapeutic nanodisc platform consisting of erythrocyte membranes and the photosensitizer IR780 is developed. With the advantages of the ultra-small size and exceptional biosafety of cell membrane-derived nanodiscs, this platform facilitates efficient accumulation and deep tissue penetration at disease sites. Upon near-infrared (NIR) irradiation, IR780 delivered via the nanodisc exhibits enhanced photothermal conversion efficiency, markedly inhibiting tumor growth in an orthotopic 4T1 breast cancer model and reducing bacterial load in a methicillin-resistant Staphylococcus aureus (MRSA) skin infection model. Furthermore, the nanodisc platform demonstrates outstanding biocompatibility in mice. In conclusion, this nanodisc system significantly extends the functional potential of cellular nanodiscs, presenting a promising strategy to address the challenges of photosensitizer delivery and biosafety in phototherapeutic applications.
研究领域:
生物医学工程
·
肿瘤学
·
微生物学
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CELL
·
2025
·
IF 42.5
Yaozhen Chen,Shouwen Chen,Zhixin Liu,Yafen Wang,Ning An,Yutong Chen,Yihao Peng,Zheng Liu,Qin Liu,Xingbin Hu
The canonical complement-mediated lysis of mature red blood cells (RBCs) leads to severe pathogenesis. However, inhibition strategies targeting complement are not always as efficient as expected, indicating that unknown mechanisms are awaiting elucidation. In this study, we investigate the intracellular events in mature RBCs following complement activation. The collected evidence demonstrates that complement-induced hemolysis is a caspase-8-dependent programmed RBC death. Furthermore, short NLRP3 (miniNLRP3) fragments in RBCs are identified to engage in the assembly of NLRP3-apoptosis-associated speck-like protein containing a CARD (ASC)-caspase-8 complex. Activated caspase-8 directly induces the proteolysis of β-spectrin, thereby disrupting the skeletal network of the RBC membrane, a process we refer to as spectosis. Spectosis signaling is also activated in autoimmune hemolytic anemia or paroxysmal nocturnal hemoglobinuria, and the inhibition of spectosis significantly reduced complement-induced hemolysis. These findings reveal a programmed death cascade in mature RBCs, which may have important implications for the treatment of hemolytic disorders.
研究领域:
免疫学
·
血液学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2018
·
IF 3.831
Guo Xi,Sun Tong,Zhong Rui,Ma Lu,You Chao,Tian Meng,Li Hao,Wang Chengwei
Chitosan oligosaccharide (COS) is known for its unique biological activities such as anti-tumor, anti-inflammatory, anti-oxidant, anti-bacterial activity, biological recognition, and immune enhancing effects, and thus continuous attracting many research interests in drug, food, cosmetics, biomaterials and tissue engineering fields. In comparison to its corresponding polymer, COS has much higher absorption profiles at the intestinal level, which results in permitting its quick access to the blood flow and potential contacting with blood components. However, the effects of COS on blood components remain unclear to date. Herein, two COS with different molecular weight (MW) were characterized by FTIR and 1H NMR, and then their effects on human blood components, including red blood cells (RBCs) (hemolysis, deformability, and aggregation), coagulation system [activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT), and the concentration of fibrinogen (Fib)], complement (C3a and C5a activation), and platelet (activation and aggregation), were comprehensively studied. In the case of RBCs, COS exhibited a low risk of hemolysis in a dose and molecular weight dependent manner and the irreversible aggregation was observed in their high concentration. For coagulation system, COS has a mild anticoagulation activity through blocking the intrinsic coagulation pathway. In addition, COS showed no effect on complement activation in C3a and C5a and on platelet activation while inhibition of platelet aggregation was evident. Finally, the mechanism that effects of COS on blood components was discussed and proposed.
研究领域:
医学
·
生物化学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NANOTECHNOLOGY
·
2018
·Vol. 29
·期 8
·084002
·
IF 3.404
Dao-Ming Zhu,Wei Xie,Yu-Sha Xiao,Meng Suo,Ming-Hui Zan,Qing-Quan Liao,Xue-Jia Hu,Li-Ben Chen,Bei Chen,Wen-Tao Wu,Li-Wei Ji,Hui-Ming Huang,Shi-Shang Guo,Xing-Zhong Zhao,Quan-Yan Liu,Wei Liu
Recently, red blood cell (RBC) membrane-coated nanoparticles have attracted much attention because of their excellent immune escapability; meanwhile, gold nanocages (AuNs) have been extensively used for cancer therapy due to their photothermal effect and drug delivery capability. The combination of the RBC membrane coating and AuNs may provide an effective approach for targeted cancer therapy. However, few reports have shown the utilization of combining these two technologies. Here, we design erythrocyte membrane-coated gold nanocages for targeted photothermal and chemical cancer therapy. First, anti-EpCam antibodies were used to modify the RBC membranes to target 4T1 cancer cells. Second, the antitumor drug paclitaxel (PTX) was encapsulated into AuNs. Then, the AuNs were coated with the modified RBC membranes. These new nanoparticles were termed EpCam–RPAuNs. We characterized the capability of the EpCam–RPAuNs for selective tumor targeting via exposure to near-infrared irradiation. The experimental results demonstrate that EpCam–RPAuNs can effectively generate hyperthermia and precisely deliver the antitumor drug PTX to targeted cells. We also validated the biocompatibility of the EpCam–RAuNs in vitro. By combining the molecularly modified targeting RBC membrane and AuNs, our approach provides a new way to design biomimetic nanoparticles to enhance the surface functionality of nanoparticles. We believe that EpCam–RPAuNs can be potentially applied for cancer diagnoses and therapies.
研究领域:
纳米技术
·
癌症研究
·
生物医学工程
·
材料科学
·
诊疗学
✓ 已验证
DOI
PubMed
高影响因子
Drug Design Development and Therapy
·
2022
·
IF 4.319
Minhua Li,Zehui Qin,Qiuxia Yu,Ziwei Huang,Juanjuan Cheng,Linjiang Zhong,Yuhong Liu,Jianhui Xie,Yucui Li,Jiannan Chen,Ruoting Zhan,Ziren Su
Background Berberine (BBR) is the primary active component of Phellodendri Chinensis Cortex (PCC), which has been traditionally used to treat inflammatory diseases. However, the discrepancy between its low bioavailability and significant therapeutic effect remains obscure. The purpose of this study was to explore the previously unsolved enigma of the low bioavailability of BBR and its appreciable anti-inflammatory effect to reveal the action mechanism of BBR and PCC. Methods The quantitative analysis of BBR and its metabolite oxyberberine (OBB) in blood and tissues was performed using high-performance liquid chromatography to investigate the conversion and distribution of BBR/OBB mediated by erythrocytes. Routine blood tests and immunohistochemical staining were used to explore the potential relationship between the amounts of monocyte/macrophage and the drug concentration in erythrocytes and tissues (liver, heart, spleen, lung, kidney, intestine, muscle, brain and pancreas). To comparatively explore the anti-inflammatory effects of BBR and OBB, the acetic acid-induced vascular permeability mice model and lipopolysaccharide-induced RAW 264.7 macrophages were employed. Results Nearly 92% of BBR existed in the erythrocytes in rats. The partition coefficient of BBR between plasma and erythrocytes (Kp/b) decreased with time. OBB was found to be the oxidative metabolite of BBR in erythrocytes. Proportion of BBR/OBB in erythrocytes changed from 9.38% to 16.30% and from 13.50% to 46.24%, respectively. There was a significant relationship between the BBR/OBB concentration in blood and monocyte depletion after a single administration of BBR. BBR/OBB was transported via erythrocytes to various tissues (liver, kidney, spleen, lung, and heart, etc), with the liver achieving the highest concentration. OBB exhibited similar anti-inflammatory effect in vitro and in vivo as BBR with much smaller dosage. Conclusion BBR was prodominantly found in erythrocytes, which was critically participated in the biodistribution, pharmacokinetics, metabolism and target delivery of BBR and its metabolite. The anti-inflammatory activity of BBR and PCC was intimately associated with the metabolism into the active congener OBB and the targeted delivery to monocytes/macrophages mediated by the erythrocytes.
研究领域:
药理学
·
中药学
·
生物化学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）