JOURNAL OF MATERIALS SCIENCE-MATERIALS IN MEDICINE
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2018
·Vol. 29
·期 5
·1-9
·
IF 2.448
Zhang Binbin,Li Yang,Wang Gaoshang,Jia Zhidong,Li Haiyan,Peng Qing,Gao Yi
Liver is one of the most important organ in the body. But there are many limitations about liver transplantation for liver failure. It is quite important to develop the xenogeneic biological liver for providing an alternation to transplantation or liver regeneration. In this paper, we proposed a method to construct a novel kind of agarose 3D-culture concave microwell array for spheroids formation of hepatic cells. Using the 3D printing method, the microwell array was fabricated with an overall size of 6.4 mm × 6.4 mm, containing 121 microwells with 400 μm width/400 μm thickness. By exploiting the Polydimethylsiloxane (PDMS) membranes as a bridge, we finally fabricated the agarose one. We co-cultured three types of liver cells with bionics design in the microwell arrays. Using the methods described above, the resulting co-formed hepatocyte spheroids maintained the high viability and stable liver-specific functions. This engineered agarose concave microwell array could be a potentially useful tool for forming the elements for biological liver support. After developing the complete system, we also would consider to scale up the application of this system. It will be not only applied to the therapy of human organ damage, but also to the development of disease models and drug screening models.
研究领域:
组织工程
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细胞生物学
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生物医学工程
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再生医学
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产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH
·
2017
·Vol. 24
·期 10
·9379-9386
·
IF 2.741
Jia Yuyu,Wang Lin,Qu Zhipeng,Wang Chaoyi,Yang Zhaoguang
Three fish species ( Carassius auratus , Pelteobagrus fulvidraco , and Squaliobarbus curriculus ) were collected from Xiang River near Changsha City, Southern China. The concentrations of heavy metals including arsenic (As), cadmium (Cd), copper (Cu), iron (Fe), manganese (Mn), lead (Pb), and zinc (Zn) in the muscle, gill, and liver of three species were determined by the inductively coupled plasma mass spectrometry method. One-way analysis of variance (ANOVA) was introduced to determine the significant variations ( p < 0.05) of heavy metals. Livers were found to accumulate Cd and Cu due to the metallothionein proteins. High levels of Mn and Pb in the gills indicated that the main uptake pathway of these heavy metals was from the water. The carnivorous species, P. fulvidraco , was found to accumulate the highest levels of toxic elements (As, Cd, and Pb), while relatively high concentrations of nutrient elements (Cu, Fe, Mn, and Zn) were accumulated in omnivorous species ( C. auratus and S. curriculus ). According to the results of Pearson’s correlation analysis, there were few significant relationships at p < 0.01 level between the concentrations of the analyzed elements and the fish sizes. The results of risk assessment indicated that exposure to the toxic heavy metals from fish muscle consumption posed no non-carcinogenic health risk to local inhabitants.
研究领域:
生态毒理学
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环境科学
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2022
·
IF 16.744
Jinwei Zhong,Qingfei Zhang,Gaizhen Kuang,Jinglin Xia,Luoran Shang
Tumor recurrence after hepatic resection is a severe challenge of current liver cancer treatment. Here we present novel multicomponent microspheres (MCMs) with co-encapsulation and spatiotemporal drug release capabilities for post-surgical liver cancer treatment and liver regeneration. The MCMs were fabricated via a stepwise microfluidic platform and were composed of a sodium alginate (ALG) shell and gelatin methacrylate (GelMA) cores. Benefitting from the “particle-in-particle” structure, the MCMs provided the possibility of loading doxorubicin (DOX) and augmenter of liver regeneration (ALR) into the shell and the cores, respectively. Besides, the MCMs enabled rapid release of DOX and more sustained release of ALR. Therefore, the dual-drug-loaded MCMs exhibited prominent effects of postsurgical tumor killing and promoting liver regeneration. We anticipate that the present MCMs have remarkable potentials as versatile drug delivery systems for post-surgical cancer therapy.
研究领域:
药学
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生物医学工程
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癌症研究
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再生医学
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产品关联
DOI
高影响因子
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY
·
2025
·
IF 4.3
Li Chen,Feifeng Chen,Jiahui Li,Mijia Li,Xiaoping Xiao,Qiang Luo,Guiyou Tian,Weixin Zhang
Isazophos, an organophosphorus insecticide, is a prevalent environmental contaminant that bioaccumulates in organisms and poses significant risks to human health. However, the organ toxicity of isazophos to aquatic organisms has not been previously characterized. The purpose of this study is to investigate the toxic effects of isazophos exposure on zabrafish liver, as well as revealing the underlying toxicological mechanisms. Acute and chronic toxicity assessments showed 72 h and 28 days lethal concentration (LC 50 ) values of 2.612 mg/L and 0.172 mg/L for zebrafish embryos and adult zebrafish, respectively. The level of superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and inflammation related genes revealed that isazophos affects early zebrafish development and causes liver damage via reactive oxygen species (ROS)-induced oxidative stress and inflammatory with upregulated pro-inflammatory factors ( il-6 , il-8 , il-1β and TNF-α ). Moreover, when exposed to isazophos, the glycogen content of the liver was decreased, while lipid accumulation was increased, and liver metabolism-related indices were changed. The ratios of pro-apoptotic genes p53 , bax / bcl-2 , caspase 9 and caspase 3 were upregulated. And the caspase3 and cleaved-caspase3 protein expression was evaluated in the isazophos group, revealing that isazophos caused aptoptotic. In conclusion, isazophos induces oxidative stress through the production of ROS, leading to the activation of pathways associated with apoptosis. The present study provides a systematic analysis of isazophos-induced hepatic effects in zebrafish liver and demonstrates that exposure to isazophos affects normal hepatic metabolism.
研究领域:
毒理学
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环境科学
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水生毒理学
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生物化学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
DRUG METABOLISM AND DISPOSITION
·
2025
·
IF 4
Yue Gao,Chenghui Cai,Wanyu Zheng,Shicheng Fan,Yifei Zhang,Yanying Zhou,Huilin Li,Jie Yang,Shaoxing Guan,Huichang Bi
Constitutive androstane receptor (CAR, NR1I3), a nuclear receptor superfamily member, plays a pivotal role in liver size regulation. Murine CAR agonist TCPOBOP was reported to induce hepatomegaly in mice, accompanied by hepatocyte hypertrophy and proliferation. However, whether CAR activation-induced hepatomegaly is reversible and the histological changes during reversal process remain elusive. In the current study, C57BL/6 mice were administered TCPOBOP for 5 days and sacrificed at different time points after drug withdrawal. The results showed that TCPOBOP-induced hepatomegaly required a long time to reverse, as evidenced by the liver-to-body weight ratio in the TCPOBOP group remained significantly higher than that in the Vehicle group even 120 days after withdrawal. CTNNB1 and CCND1 staining indicated a reduction in hepatocyte size and proliferating cells. To investigate the involved mechanisms, we measured proteins associated with hepatomegaly and liver regeneration termination. The results suggested that YAP, C-MYC, CTNNB1, FOXM1 and HNF4α changed significantly after TCPOBOP withdrawal and functioned at different stages during reversal. Furthermore, we established a UPLC-MS/MS method to quantify TCPOBOP concentration. The results indicated a long-term hepatic retention of TCPOBOP, which constantly activated CAR and led to sustained hepatomegaly after TCPOBOP withdrawal. Overall, these findings revealed the reversibility of CAR activation-induced hepatomegaly and provided new insights into the safety of CAR as a drug target. Additionally, the results highlighted the importance of considering long-term TCPOBOP accumulation in the liver to avoid potential adverse effects and experimental biases.
研究领域:
药理学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BULLETIN OF ENVIRONMENTAL CONTAMINATION AND TOXICOLOGY
·
2013
·Vol. 91
·期 5
·522-525
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IF 1.105
Li Yong-Fang,Yang Zhong-Zhi,Fan Jing,Zhu Yong
Five higher chlorinated benzenes (including hexachlorobenzene (HCB), pentachlorobenzene (PeCB) and three isomers of tetrachlorobenzens) were measured in the livers of grass carp and common carp collected from five markets in Xinxiang city, China. HCB and PeCB were detected in all samples. The major component of the higher CBs residue was HCB and significant correlations existed between HCB and PeCB in both grass carp and common carp livers. The ratio range of HCB/PeCB in grass carp and common carp were 3.4–6.2 and 4.9–7.7, respectively, which implied the sources of higher CBs originate mainly from the revolatilization of industrial HCB with a minor impact from PeCB.
研究领域:
环境科学
·
毒理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CURRENT ISSUES IN MOLECULAR BIOLOGY
·
2022
·Vol. 44
·期 2
·470-482
·
IF 2.976
Jiawang Tao,Yan Chen,Yuanqi Zhuang,Ruzhi Wei,Anteneh Getachew,Tingcai Pan,Fan Yang,Yinxiong Li
Liver regeneration is a complicated biological process orchestrated by various liver resident cells. Hepatic cell proliferation and reconstruction of the hepatic architecture involve multiple signaling pathways. It has been reported that the Hh signal is involved in liver regeneration. However, the signal transduction pathways and cell types involved are ill studied. This study aimed to investigate hedgehog signal response cell types and the specific molecular mechanism involved in the process of liver regeneration. Partial hepatectomy (PH) of 70% was performed on ICR (Institute of Cancer Research) mice to study the process of liver regeneration. We found that the hedgehog signal was activated significantly after PH, including hedgehog ligands, receptors and intracellular signaling molecules. Ligand signals were mainly expressed in bile duct cells and non-parenchymal hepatic cells, while receptors were expressed in hepatocytes and some non-parenchymal cells. Inhibition of the hedgehog signal treated with vismodegib reduced the liver regeneration rate after partial hepatectomy, including inhibition of hepatic cell proliferation by decreasing Cyclin D expression and disturbing the cell cycle through the accumulation of Cyclin B. The current study reveals the important role of the hedgehog signal and its participation in the regulation of hepatic cell proliferation and the cell cycle during liver regeneration. It provides new insight into the recovery of the liver after liver resection.Keywords:vismodegib;smoothened;liver regeneration;hedgehog signaling;mitosis
研究领域:
分子生物学
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细胞生物学
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肝病学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF APPLIED TOXICOLOGY
·
2025
·
IF 2.8
Kai Wang,Aneela Perveen,Jiakun Shen,Niaz Ali Kaka,Yansen Li,Dan Shen,Chunmei Li
T-2 mycotoxin is a highly toxic type A trichothecene mycotoxin that widely contaminates livestock feed, posing a serious threat to animal and human health. Long-term exposure can lead to immunosuppression, growth retardation, and liver damage, causing significant economic losses to the livestock industry. Offspring are particularly susceptible to maternal dietary influences during pregnancy and lactation. This research aimed to evaluate the impact of T-2 mycotoxin exposure on both dams and their pups. Thirty pregnant mice were randomly allocated into three groups ( n = 10). From gestational day 14 to lactational day 21, the dams received gavage doses of T-2 mycotoxin at concentrations of 0, 0.005, and 0.05 mg/kg/day. Randomly selected one male pup and one female pup from each dam were sacrificed on LD 1, 7, and 21; dams were dosed until the day they were sacrificed. T-2 mycotoxin decreased the relative body/organ weights of the dams and offspring ( p < 0.05). Moreover, T-2 mycotoxin-induced oxidative stress in dams and offspring increased the malondialdehyde content, which led to reduced activities of antioxidant enzymes, including catalase, superoxide dismutase, and glutathione peroxidase, and total antioxidant capacity in the serum and liver ( p < 0.05). T-2 mycotoxin induced histomorphological changes in the liver and early involution of the mammary gland acini in dams. The concentrations of liver-metabolizing enzymes such as glutamic oxaloacetic transaminase and glutamic pyruvic transaminase increased in offspring ( p < 0.05). The serum insulin-like growth factor-1 level in offspring was decreased, which may impair the development of vital organs such as the liver, kidneys, and spleen in offspring. Consequently, the body weight and length of the offspring of exposed dams decreased. This study revealed that T-2 mycotoxin exposure during late gestation and entire lactation harms dams, damages mammary gland acini, alters liver biochemistry, induces oxidative stress, and delays offspring growth while also impairing maternal weight gain during lactation.
研究领域:
毒理学
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生殖生物学
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发育生物学
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肝脏病学
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营养毒理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2015
·
IF 4.383
Dong Dong,Xiao Wang,Huailing Wang,Xingwang Zhang,Yifei Wang,Baojian Wu
Introduction SNX-2112 is a promising anticancer agent but has poor solubility in both water and oil. In the study reported here, we aimed to develop a nanocrystal formulation for SNX-2112 and to determine the pharmacokinetic behaviors of the prepared nanocrystals.Methods Nanocrystals of SNX-2112 were prepared using the wet-media milling technique and characterized by particle size, differential scanning calorimetry, drug release, etc. Physiologically based pharmacokinetic (PBPK) modeling was undertaken to evaluate the drug’s disposition in rats following administration of drug cosolvent or nanocrystals.Results The optimized SNX-2112 nanocrystals (with poloxamer 188 as the stabilizer) were 203 nm in size with a zeta potential of −11.6 mV. In addition, the nanocrystals showed a comparable release profile to the control (drug cosolvent). Further, the rat PBPK model incorporating the parameters of particulate uptake (into the liver and spleen) and of in vivo drug release was well fitted to the experimental data following administration of the drug nanocrystals. The results reveal that the nanocrystals rapidly released drug molecules in vivo, accounting for their cosolvent-like pharmacokinetic behaviors. Due to particulate uptake, drug accumulation in the liver and spleen was significant at the initial time points (within 1 hour).Conclusion The nanocrystals should be a good choice for the systemic delivery of the poorly soluble drug SNX-2112. Also, our study contributes to an improved understanding of the in vivo fate of nanocrystals.
研究领域:
药理学
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纳米医学
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肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Hu Chen,Minglei Teng,Qihui Hu,Xiaoliu Liang,Hui Liu,Zhenjie Li,Xing Gao,Yisheng Peng,Xiaoyong Wang,Syed Faheem Askari Rizvi,Yi Lv,Hongwei Cheng,Rui Tao,Gang Liu
Anatomical hepatectomy is a widely employed surgical technique due to its capacity to excise hepatic lesions and minimize risk variables associated with postoperative recurrence. However, preserving the anatomical and functional integrity of the liver remains a critical concern and a significant challenge in determining the boundaries of targeted liver segments. This study utilized a super-stable pure-nanomedicine formulation technology (SPFT) to synthesize methylene blue nanosheets (nanoMB) without external carrier, nanoMB did not alter the chemical composition of methylene blue (MB), it was purely a physical aggregation of molecules. The nanosize and morphology of nanoMB enhanced the internalization and retention in hepatocytes and liver tissues, addressing the limitations of unclear staining due to the rapid diffusion of MB during liver segment resection. The in vivo model of blue staining of liver segments in rats and rabbits confirmed that nanoMB can extend the staining duration of liver segments by over 3 h, whereas free MB continues for <1 min, thereby addressing the time constraints associated with liver resection. In subsequent human clinical trials, a single low-dose nanoMB injection was employed to mark hepatic segment boundaries during anatomical hepatectomy for hepatocellular carcinoma and hepatolithiasis. The boundaries continued to be distinct for over 30 min, effectively guiding the surgical resection. The postoperative liver function recovered to normal, with no complications or disease recurrence reported. In conclusion, carrier-free nanomedicine enhances hepatic visualization by improving cellular uptake and hepatic segment retention. This advancement facilitates precise surgery and establishes a new paradigm for translational research from bench to clinic.
研究领域:
纳米医学
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肝脏外科
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转化医学
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生物医学工程
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肿瘤外科学
✓ 已验证
产品关联
DOI
高影响因子
International Journal of Nanomedicine
·
2024
·
IF 6.6
Xiangdong Gongye,Peng Xia,Tianyin Ma,Yibo Chai,Zhang Chen,Yimin Zhu,Chengming Qu,Jie Liu,Wing Wa Guo,Minghe Zhang,Yingyi Liu,Ming Tian,Yufeng Yuan
Background The liver’s regenerative capacity allows it to repair itself after injury. Extracellular vesicles and particles (EVPs) in the liver’s interstitial space are crucial for signal transduction, metabolism, and immune regulation. Understanding the role and mechanism of liver-derived EVPs in regeneration is significant, particularly after partial hepatectomy, where the mechanisms remain unclear.Methods A 70% hepatectomy model was established in mice, and EVPs were isolated and characterized using electron microscopy, nanocharacterization, and Western blot analysis. Combined metabolomic and transcriptomic analyses revealed β-sitosterol enrichment in EVPs and activation of the Hedgehog signaling pathway during regeneration. The role of β-sitosterol in EVPs on the Hedgehog pathway and its targets were identified using qRT-PCR, Western blot analysis. The regulation of carnitine synthesis by this pathway was determined using a dual luciferase assay. The effect of a β-sitosterol diet on liver regeneration was verified in mice.Results After 70% hepatectomy, the liver successfully regenerated without liver failure or death. At 24 hours post-surgery, tissue staining showed transient regeneration-associated steatosis (TRAS), with increased Ki67 positivity at 48 hours. EVPs displayed a spherical lipid bilayer structure with particle sizes of 70–130 nm. CD9, CD63, and CD81 in liver-derived EVPs were confirmed. Transcriptomic and metabolomic analyses showed EVPs supplementation significantly promoted carnitine synthesis and fatty acid oxidation. Tissue staining confirmed accelerated TRAS resolution and enhanced liver regeneration with EVP supplementation. Mass spectrometry identified β-sitosterol in EVPs, which binds to Smo protein, activating the Hedgehog pathway. This led to the nuclear transport of Gli3, stimulating Setd5 transcription and inducing carnitine synthesis, thereby accelerating fatty acid oxidation. Mice with increased β-sitosterol intake showed faster TRAS resolution and liver regeneration compared to controls.Conclusion Liver-derived EVPs promote regeneration after partial hepatectomy. β-sitosterol from EVPs accelerates fatty acid oxidation and promotes liver regeneration by activating Hedgehog signaling pathway.
研究领域:
肝病学
·
分子生物学
·
再生医学
·
代谢组学
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转录组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL POLLUTION
·
2020
·
IF 6.793
Zhiyuan Meng,Sinuo Tian,Wei Sun,Li Liu,Sen Yan,Shiran Huang,Wentao Zhu,Zhiqiang Zhou
Prothioconazole (PTC), a popular agricultural fungicide , and its main metabolite prothioconazole-desthio (PTCd) are receiving great attention due to their toxicological effects in the non-target organisms. This study investigated their dosage-dependent (1 and 5 mg/kg BW/day) toxicological effects on oxidative stress and metabolic profiles of liver and kidney tissues using male mice. PTC and PTCd significantly inhibited the growth phenotype including body weights gain, liver and kidney indices. Furthermore, these effects were deeply investigated using the biomarkers of oxidative stress, and metabolomics. Notably, these effects were dose and tissue-dependent. Specifically, the more serious impacts involving oxidative stress and metabolic disorders were observed in the high concentration treatment groups. Also, the liver tissue was more severely affected than the kidney tissue. Lastly, the change in oxidative stress biomarkers and metabolomics profile revealed that PTCd induced more severe toxic effects than the parent compound PTC. In brief, these results indicate that exposure to PTC and PTCd could cause potential health risks in mammals.
研究领域:
毒理学
·
环境科学
·
代谢组学
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）