Regulation and Release of Vasoactive Endoglin by Brain Endothelium in Response to Hypoxia/Reoxygenation in Stroke

In large vessel occlusion stroke, recanalization to restore cerebral perfusion is essential but not necessarily sufficient for a favorable outcome. Paradoxically, in some patients, reperfusion carries the risk of increased tissue damage and cerebral hemorrhage. Experimental and clinical data suggest that endothelial cells, representing the interface for detrimental platelet and leukocyte responses, likely play a crucial role in the phenomenon referred to as ischemia/reperfusion (I/R)-injury, but the mechanisms are unknown. We aimed to determine the role of endoglin in cerebral I/R-injury; endoglin is a membrane-bound protein abundantly expressed by endothelial cells that has previously been shown to be involved in the maintenance of vascular homeostasis. We investigated the expression of membranous endoglin (using Western blotting and RT-PCR) and the generation of soluble endoglin (using an enzyme-linked immunosorbent assay of cell culture supernatants) after hypoxia and subsequent reoxygenation in human non-immortalized brain endothelial cells. To validate these in vitro data, we additionally examined endoglin expression in an intraluminal monofilament model of permanent and transient middle cerebral artery occlusion in mice. Subsequently, the effects of recombinant human soluble endoglin were assessed by label-free impedance-based measurement of endothelial monolayer integrity (using the xCELLigence DP system) and immunocytochemistry. Endoglin expression is highly inducible by hypoxia in human brain endothelial monolayers in vitro, and subsequent reoxygenation induced its shedding. These findings were corroborated in mice during MCAO; an upregulation of endoglin was displayed in the infarcted hemispheres under occlusion, whereas endoglin expression was significantly diminished after transient MCAO, which is indicative of shedding. Of note is the finding that soluble endoglin induced an inflammatory phenotype in endothelial monolayers. The treatment of HBMEC with endoglin resulted in a decrease in transendothelial resistance and the downregulation of VE-cadherin. Our data establish a novel mechanism in which hypoxia triggers the initial endothelial upregulation of endoglin and subsequent reoxygenation triggers its release as a vasoactive mediator that, when rinsed into adjacent vascular beds after recanalization, can contribute to cerebral reperfusion injury.     

聚乙二醇为分散剂制备纳米生物活性玻璃粉体

采用溶胶-凝胶共沉淀方法结合冷冻干燥技术制备颗粒尺寸在纳米级的生物活性玻璃(NBG),研究了加入分散剂聚乙二醇(PEG-10000)对玻璃颗粒的分散性能、微观形貌和生物活性的影响.结果表明:没有加入PEG制得的纳米生物活性玻璃颗粒呈现不规则形态,粒径小于50 nm.加有PEG的玻璃颗粒形状趋于规则的球形,分散性大大提高,颗粒粒径在40～100 nm,而且加入PEG的浓度越高,制备的颗粒粒径越小.通过比较纳米级的生物活性玻璃与溶胶-凝胶生物活性玻璃在模拟人体体液(SBF)中的表面矿化研究,发现纳米生物活性玻璃比溶胶-凝胶生物活性玻璃有更高的生物活性.     

丹参三七不同配比对缺氧复氧损伤人脐静脉内皮细胞的保护作用

研究了丹参、三七及其以不同质量比例配伍对缺氧复氧(H/R)人脐静脉内皮细胞(HUVECs)的保护作用。采用全自动生化分析仪测定了培养液中乳酸脱氢酶(LDH)漏出率。实验结果显示,正常对照组、H/R模型组的LDH漏出率分别为0.212与0.309,说明H/R引起HUVECs的LDH漏出率增加。而丹参、三七按质量比10∶0、10∶1、5∶1、5∶3、1∶1、3∶5、1∶5、1∶10、0∶10配伍后,使H/R损伤HUVECs的LDH漏出率分别降低为0.218、0.240、0.247、0.239、0.230、0.241、0.247、0.242、0.227,其中只有丹参三七质量比为10∶0、5∶3、1∶1及0∶10与模型组比有显著性差异,因此,丹参、三七及丹参三七质量比为5∶3、1∶1配伍,均可保护H/R诱导血管内皮损伤。     

Reduced cytotoxicity of insulin-immobilized CdS quantum dots using PEG as a spacer

Cytotoxicity is a severe problem for cadmium sulfide nanoparticles (CSNPs) in biological systems. In this study, mercaptoacetic acid-coated CSNPs, typical semiconductor Q-dots, were synthesized in aqueous medium by the arrested precipitation method. Then, amino-terminated polyethylene glycol (PEG) was conjugated to the surface of CSNPs (PCSNPs) in order to introduce amino groups to the surface. Finally, insulin was immobilized on the surface of PCSNPs (ICSNPs) to reduce cytotoxicity as well as to enhance cell compatibility. The presence of insulin on the surface of ICSNPs was confirmed by observing infrared absorptions of amide I and II. The mean diameter of ICSNPs as determined by dynamic light scattering was about 38 nm. Human fibroblasts were cultured in the absence and presence of cadmium sulfide nanoparticles to evaluate cytotoxicity and cell compatibility. The results showed that the cytotoxicity of insulin-immobilized cadmium sulfide nanoparticles was significantly suppressed by usage of PEG as a spacer. In addition, cell proliferation was highly facilitated by the addition of ICSNPs. The ICSNPs used in this study will be potentials to be used in bio-imaging applications.     

自组装法制备CMCS/PEG纳米粒子及其pH值响应性研究

以壳聚糖(CS)为原料与氯乙酸反应制备羧甲基壳聚糖(CMCS),再将聚乙二醇(PEG)和CMCS以不同的质量比溶解在不同pH值的溶液中,通过氢键相互作用自组装形成CMCS/PEG纳米粒子,并研究其粒径大小与二者配比和溶液pH值之间的关系。结果表明,不同配比下的粒子粒径均随pH值的增大先增大后减小;当pH5时,在相同pH值溶液中,随着PEG比例的增加,粒子的粒径先减小后增大,在pH=1.22、PEG∶CMCS=4∶1时粒径最小,约为160nm;当pH≥5时,在相同pH值溶液中,粒径随PEG用量的增加而增大;通过自组装法制备的CMCS/PEG纳米粒子粒径大小具有pH值响应性。     

Role of Mitochondrial Pathways in Cell Apoptosis during He-Patic Ischemia/Reperfusion Injury

Hepatic ischemia-reperfusion injury is a major cause of post-operative hepatic dysfunction and liver failure after transplantation. Mitochondrial pathways can be either beneficial or detrimental to hepatic cell apoptosis during hepatic ischemia/reperfusion injury, depending on multiple factors. Hepatic ischemia/reperfusion injury may be induced by opened mitochondrial permeability transition pore, released apoptosis-related proteins, up-regulated B-cell lymphoma-2 gene family proteins, unbalanced mitochondrial dynamics, and endoplasmic reticulum stress, which are integral parts of mitochondrial pathways. In this review, we discuss the role of mitochondrial pathways in apoptosis that account for the most deleterious effect of hepatic ischemia/reperfusion injury.     

Cyclic Nigerosyl-Nigerose as Oxygen Nanocarrier to Protect Cellular Models from Hypoxia/Reoxygenation Injury: Implications from an In Vitro Model

Heart failure (HF) prevalence is increasing among the aging population, and the mortality rate remains unacceptably high despite improvements in therapy. Myocardial ischemia (MI) and, consequently, ischemia/reperfusion injury (IRI), are frequently the basis of HF development. Therefore, cardioprotective strategies to limit IRI are mandatory. Nanocarriers have been proposed as alternative therapy for cardiovascular disease. Controlled reoxygenation may be a promising strategy. Novel nanocarriers, such as cyclic nigerosyl-nigerose (CNN), can be innovative tools for oxygen delivery in a controlled manner. In this study we analyzed new CNN-based formulations as oxygen nanocarriers (O₂-CNN), and compared them with nitrogen CNN (N₂-CNN). These different CNN-based formulations were tested using two cellular models, namely, cardiomyoblasts (H9c2), and endothelial (HMEC) cell lines, at different concentrations. The effects on the growth curve during normoxia (21% O₂, 5% CO₂ and 74% N₂) and their protective effects during hypoxia (1% O₂, 5% CO₂ and 94% N₂) and reoxygenation (21% O₂, 5% CO₂ and 74% N₂) were studied. Neither O₂-CNN nor N₂-CNN has any effect on the growth curve during normoxia. However, O₂-CNN applied before hypoxia induces a 15–30% reduction in cell mortality after hypoxia/re-oxygenation when compared to N₂-CNN. O₂-CNN showed a marked efficacy in controlled oxygenation, which suggests an interesting potential for the future medical application of soluble nanocarrier systems for MI treatment.     

Sphingosine as a New Antifungal Agent against Candida and Aspergillus spp.

This study investigated whether sphingosine is effective as prophylaxis against Aspergillus spp. and Candida spp. In vitro experiments showed that sphingosine is very efficacious against A. fumigatus and Nakeomyces glabrataa (formerly named C. glabrata). A mouse model of invasive aspergillosis showed that sphingosine exerts a prophylactic effect and that sphingosine-treated animals exhibit a strong survival advantage after infection. Furthermore, mechanistic studies showed that treatment with sphingosine leads to the early depolarization of the mitochondrial membrane potential (Δψm) and the generation of mitochondrial reactive oxygen species and to a release of cytochrome C within minutes, thereby presumably initiating apoptosis. Because of its very good tolerability and ease of application, inhaled sphingosine should be further developed as a possible prophylactic agent against pulmonary aspergillosis among severely immunocompromised patients.     

The Interplay between Autophagy and NLRP3 Inflammasome in Ischemia/Reperfusion Injury

Ischemia/reperfusion (I/R) injury is characterized by a limited blood supply to organs, followed by the restoration of blood flow and reoxygenation. In addition to ischemia, blood flow recovery can also lead to very harmful injury, especially inflammatory injury. Autophagy refers to the transport of cellular materials to the lysosomes for degradation, leading to the conversion of cellular components and offering energy and macromolecular precursors. It can maintain the balance of synthesis, decomposition and reuse of the intracellular components, and participate in many physiological processes and diseases. Inflammasomes are a kind of protein complex. Under physiological and pathological conditions, as the cellular innate immune signal receptors, inflammasomes sense pathogens to trigger an inflammatory response. TheNLRP3 inflammasome is the most deeply studied inflammasome and is composed of NLRP3, the adaptor apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and pro-caspase-1. Its activation triggers the cleavage of pro-interleukin (IL)-1β and pro-IL-18 mediated by caspase-1 and promotes a further inflammatory process. Studies have shown that autophagy and the NLRP3 inflammasome play an important role in the process of I/R injury, but the relevant mechanisms have not been fully explained, especially how the interaction between autophagy and the NLRP3 inflammasome participates in I/R injury, which remains to be further studied. Therefore, we reviewed the recent studies about the interplay between autophagy and the NLRP3 inflammasome in I/R injury and analyzed the mechanisms to provide the theoretical references for further research in the future.     

DRAM1 Protects Neuroblastoma Cells from Oxygen-Glucose Deprivation/Reperfusion-Induced Injury via Autophagy

DNA damage-regulated autophagy modulator protein 1 (DRAM1), a multi-pass membrane lysosomal protein, is reportedly a tumor protein p53 (TP53) target gene involved in autophagy. During cerebral ischemia/reperfusion (I/R) injury, DRAM1 protein expression is increased, and autophagy is activated. However, the functional significance of DRAM1 and the relationship between DRAM1 and autophagy in brain I/R remains uncertain. The aim of this study is to investigate whether DRAM1 mediates autophagy activation in cerebral I/R injury and to explore its possible effects and mechanisms. We adopt the oxygen-glucose deprivation and reperfusion (OGD/R) Neuro-2a cell model to mimic cerebral I/R conditions in vitro, and RNA interference is used to knock down DRAM1 expression in this model. Cell viability assay is performed using the LIVE/DEAD viability/cytotoxicity kit. Cell phenotypic changes are analyzed through Western blot assays. Autophagy flux is monitored through the tandem red fluorescent protein–Green fluorescent protein–microtubule associated protein 1 light chain 3 (RFP–GFP–LC3) construct. The expression levels of DRAM1 and microtubule associated protein 1 light chain 3II/I (LC3II/I) are strongly up-regulated in Neuro-2a cells after OGD/R treatment and peaked at the 12 h reperfusion time point. The autophagy-specific inhibitor 3-Methyladenine (3-MA) inhibits the expression of DRAM1 and LC3II/I and exacerbates OGD/R-induced cell injury. Furthermore, DRAM1 knockdown aggravates OGD/R-induced cell injury and significantly blocks autophagy through decreasing autophagosome-lysosome fusion. In conclusion, our data demonstrate that DRAM1 knockdown in Neuro-2a cells inhibits autophagy by blocking autophagosome-lysosome fusion and exacerbated OGD/R-induced cell injury. Thus, DRAM1 might constitute a new therapeutic target for I/R diseases.     

Synthesis of PEG/TDI/F6 Adducts and Utilization as Water/Oil Repellents and Oily Stain Release Finishes for Cotton Fabric

Abstract

Four polyethylene glycol (PEG)/2,4-toluene diisocyante (TDI)/ perfluorinated aliphatic alcohols mixture (F6) adducts were prepared by reacting equimolar ratios of PEG (300, 600, 1000, or 2000), TDI, and F6 at 90°C for 90 min. All adducts, except that based on PEG 300 were water dispersible. These dispersions were used as water/oil repellent and oily stain release finishes for cotton fabric, via incorporation in a finishing bath containing DMDHEU. Factors affecting finishing process, using an adduct based on PEG 1000, such as DMDHEU concentration (0–60 g/l), adduct concentration (10–40 g/l), curing time (1–5 min), and temperature (140–170°C) were studied. Optimal performance properties of treated fabric, namely wrinkle recovery angle (WRA), %N, water/oil and stain release ratings, tensile strength, and breaking extension, were obtained using a padding bath containing DMDHEU (50 g/l), the adduct (30 g/l), and MgCl₂ · 6H₂O₂ (5 g/l), drying at 100°C/5 min and curing at 160°C/3 min. The inclusion of hydrophilic PEG segments in the adduct structure weakens the hydrophobic effect of perfluorinted segments, where the water repellency rating does not exceed a ceiling of 50, under the conditions employed. However, the adduct has a dual activity, where it repels oily stain in air and releases them during washing. A comparison among performance properties of fabric treated with adducts based on PEG 600, 1000, and 2000, showed that the fabric properties are practically the same, with little drops in WRA, %N, and oil repellency rating upon increasing PEG molecular weight from 600 to 2000.     

1,2,3,4,6-O-Pentagalloylglucose Protects against Acute Lung Injury by Activating the AMPK/PI3K/Akt/Nrf2 Pathway

An acute lung injury (ALI) is a serious lung disease with a high mortality rate, warranting the development of novel therapies. Previously, we reported that 1,2,3,4,6-O-pentagalloylglucose (PGG) could afford protection against ALI, however, the PGG-mediated protective effects remain elusive. Herein, PGG (60 and 30 mg/kg) markedly inhibited the lung wet/drug weight ratio and attenuated histological changes in the lungs (p < 0.05). A pretreatment with PGG (60 and 30 mg/kg) reduced the number of total leukocytes and the production of pro-inflammatory cytokines IL-6 and IL-1β in bronchoalveolar lavage fluid (p < 0.05). In addition, PGG (60 and 30 mg/kg) also attenuated oxidative stress by reducing the formation of formation and the depletion of superoxide dismutase to treat an ALI (p < 0.05). To further explore the PGG-induced mechanism against an ALI, we screened the PGG pathway using immunohistochemical analysis, immunofluorescence assays, and Western blotting (WB). WB revealed that the expression levels of adenosine monophosphate-activated protein kinase phosphorylation (p-AMPK), phosphoinositide 3-kinase (PI3K), protein kinase B phosphorylation (P-Akt), and nuclear factor erythroid 2-related factor (Nrf2) were significantly higher in the PGG group (60 and 30 mg/kg) than in the lipopolysaccharide group (p < 0.05); these findings were confirmed by the immunohistochemical and immunofluorescence results. Accordingly, PGG could be effective against an ALI by inhibiting inflammation and oxidative stress via AMPK/PI3K/Akt/Nrf2 signaling, allowing for the potential development of this as a natural drug against an ALI.     

Synthesis and Characterization of Xylan Grafted with Polyethylene Glycol in Ionic Liquid and Their Use as Moisture‐Absorption/Retention Biomaterials

The objective of this study is to broaden the application of xylan as moisture‐absorption/retention biomaterials by grafting polyethylene glycol (PEG) on xylan backbone. Ionic liquid 1‐allyl‐3‐methylimidazolium chloride ([Amim]Cl) and 4,4‐diphenylmethane diisocyanate are used as reaction media and coupling reagent, respectively. FT‐IR, ¹H‐NMR, and gel permeation chromatography analyses indicate the successful occurrence of the grafting reaction. Thermogravimetric analysis/derivative thermogravimetry indicates that the thermal stability of xylan increases after the grafting of the PEG side chains. With an increase of the degree of substitution of xylan‐g‐PEG, the molecular weight (M_w) of PEG side chains (1000 and 5000 g mol^?1), and the relative humidity of environment, the moisture‐absorption/retention ratio of xylan‐g‐PEG increases. To evaluate the biodegradability/biocompatibility of this promising material, the ratio of biochemical oxygen demand to chemical oxygen demand of xylan‐g‐PEG and the cytotoxicity are tested on the samples. The results indicate that PEG‐modified xylan has great potential as moisture‐absorption/retention biomaterials.

     

Acrylic acid/allyloxy polyethylene glycol copolymer with methoxysilicon end groups as a highly effective dispersant for nano-SiO2 aqueous system

In order to improve the dispersity and stability of nano-SiO₂ aqueous system with high solid content, acrylic acid/allyloxy polyethylene glycol copolymer dispersants with methoxysilicon end groups (KH590-AA_x-APEG_y) were synthesized by photopolymerization. After adding KH590-AA_x-APEG_y into the nano-SiO₂ aqueous system, the viscosity, the curing time, the particle size, and the zeta potential of these systems were respectively measured. The results showed that introducing polyethylene glycol chain into the dispersant was beneficial to better exerting its electrostatic repulsion and steric hindrance effects and further improving the dispersibility of the nano-SiO₂ aqueous system. Moreover, the dispersion stability of SiO₂ nanoparticles in water was closely related to the composition, the molecular weight, and the addition amount of KH590-AA_x-APEG_y and the solid content. When the molecular weight of KH590-AA_x-APEG_y was 3200 g mol⁻¹ and its addition amount was 0.1 wt %, the nano-SiO₂ aqueous system with 20 wt % solid content showed the best dispersity and stability. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020 , 137, 48617.     

Hepatocyte-Derived Igκ Exerts a Protective Effect against ConA-Induced Acute Liver Injury

Immunoglobulin (Igκ) has been reported to be expressed in sorted liver epithelial cells of μMT mice, and the sequence characteristics of hepatocyte-derived Igκ were different from those of classical B-cell-derived Igκ. However, the physiological function of hepatocyte-derived Igκ is still unclear. The expression of Igκ was firstly identified in primary hepatocytes and normal liver cell line (NCTC1469), and hepatocyte-derived Igκ expression was elevated and displayed unique localization in hepatocytes of concanavalin A (ConA)-induced hepatitis model. Moreover, Igκ knockout mice were more sensitive to ConA-induced hepatitis and had higher serum aspartate aminotransferase (AST) levels, more severe histological injury and a greater number of terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate nick end-labeling (TUNEL)-positive cells as compared with littermate controls. Furthermore, knockdown of Igκ in primary hepatocytes and NCTC1469 cells led to accelerated activation of the mitochondrial death pathway and caspase-3 cleavage in vitro, which might be related to inhibition of NF-κB signaling pathway and activation of JNK via the cytoskeleton dynamics. Taken together, these results indicate that hepatocyte-derived Igκ mediates cellular resistance to ConA-induced liver injury by inhibiting activation of caspase-3 and the mitochondrial death pathway, suggesting that Igκ plays an important role in hepatocyte survival and exerts a protective effect against ConA-induced liver injury in mice.     

Maleated Natural Rubber as a Coupling Agent for Recycled High Density Polyethylene/Natural Rubber/Kenaf Powder Biocomposites

Kenaf powder (KP) was incorporated into recycled high density polyethylene (rHDPE)/natural rubber (NR) blend using an internal mixer at 165°C and rotor speed of 50 rpm. The tensile strength and elongation at break of the composites decreased, while the tensile modulus increased with increasing filler loading. The water absorption was found to increase as the filler content increased. The maleic anhydride grafted natural rubber was prepared and used to enhance the composites performance. The addition of MANR as a coupling agent improved the tensile properties of rHDPE/NR/KP biocomposites. The water absorption was also reduced with the addition of MANR.     

阴离子-非离子共模板法制备Pt/K/TiO2-Al2O3催化剂

采用阴离子型表面活性剂SDS（十二烷基硫酸钠）和非离子型表面活性剂OP（聚乙二醇辛基苯基醚）做为共模板剂,采用柠檬酸络合-有机模板剂分解耦合法成功制备了介孔TiO2-Al2O3载体及其负载型NSR催化剂。BET测试结果表明：采用共模板剂法制备的TiO2-Al2O3载体比表面积高达398 m2/g,而使用单一模板剂CTAB或传统共沉淀法制备的载体其比表面积分别只有373和250 m2/g。H2-Chemisorption、XRD和NH3-TPD等表征结果显示,该载体同时具有更高的Pt分散度和表面酸量。负载后,所得Pt/K/TiO2-Al2O3催化剂表现出更高的NOx储存量（比传统共沉淀法样品提高62.1%）和抗硫性能（硫化再生效率达到91%）。     

A Rheostat of Ceramide and Sphingosine-1-Phosphate as a Determinant of Oxidative Stress-Mediated Kidney Injury

Reactive oxygen species (ROS) modulate sphingolipid metabolism, including enzymes that generate ceramide and sphingosine-1-phosphate (S1P), and a ROS-antioxidant rheostat determines the metabolism of ceramide-S1P. ROS induce ceramide production by activating ceramide-producing enzymes, leading to apoptosis, while they inhibit S1P production, which promotes survival by suppressing sphingosine kinases (SphKs). A ceramide-S1P rheostat regulates ROS-induced mitochondrial dysfunction, apoptotic/anti-apoptotic Bcl-2 family proteins and signaling pathways, leading to apoptosis, survival, cell proliferation, inflammation and fibrosis in the kidney. Ceramide inhibits the mitochondrial respiration chain and induces ceramide channel formation and the closure of voltage-dependent anion channels, leading to mitochondrial dysfunction, altered Bcl-2 family protein expression, ROS generation and disturbed calcium homeostasis. This activates ceramide-induced signaling pathways, leading to apoptosis. These events are mitigated by S1P/S1P receptors (S1PRs) that restore mitochondrial function and activate signaling pathways. SphK1 promotes survival and cell proliferation and inhibits inflammation, while SphK2 has the opposite effect. However, both SphK1 and SphK2 promote fibrosis. Thus, a ceramide-SphKs/S1P rheostat modulates oxidant-induced kidney injury by affecting mitochondrial function, ROS production, Bcl-2 family proteins, calcium homeostasis and their downstream signaling pathways. This review will summarize the current evidence for a role of interaction between ROS-antioxidants and ceramide-SphKs/S1P and of a ceramide-SphKs/S1P rheostat in the regulation of oxidative stress-mediated kidney diseases.     

Honokiol Acts as a Potent Anti-Fibrotic Agent in the Liver through Inhibition of TGF-β1/SMAD Signaling and Autophagy in Hepatic Stellate Cells

Chronic liver injury may result in hepatic fibrosis, which can progress to cirrhosis and eventually liver failure. There are no drugs that are specifically approved for treating hepatic fibrosis. The natural product honokiol (HNK), a bioactive compound extracted from Magnolia grandiflora, represents a potential tool in the management of hepatic fibrosis. Though HNK has been reported to exhibit suppressive effects in a rat fibrosis model, the mechanisms accounting for this suppression remain unclear. In the present study, the anti-fibrotic effects of HNK on the liver were evaluated in vivo and in vitro. In vivo studies utilized a murine liver fibrosis model, in which fibrosis is induced by treatment with carbon tetrachloride (CCl₄). For in vitro studies, LX-2 human hepatic stellate cells (HSCs) were treated with HNK, and expression of markers of fibrosis, cell viability, the transforming growth factor-β (TGF-β1)/SMAD signaling pathway, and autophagy were analyzed. HNK was well tolerated and significantly attenuated CCl₄-induced liver fibrosis in vivo. Moreover, HNK decreased HSC activation and collagen expression by downregulating the TGF-β1/SMAD signaling pathway and autophagy. These results suggest that HNK is a new potential candidate for the treatment of hepatic fibrosis through suppressing both TGF-β1/SMAD signaling and autophagy in HSCs.     

Hepatoprotective Effects of Albumin-Encapsulated Nanoparticles of a Curcumin Derivative COP-22 against Lipopolysaccharide/D-Galactosamine-Induced Acute Liver Injury in Mice

Acute liver injury (ALI) is a severe syndrome and can further develop into acute liver failure (ALF) which can lead to high mortality and cause irreversible liver injuries in the clinic. Liver transplantation is the most common treatment; however, liver donors are lacking, and the progression of ALF is rapid. Nanoparticles can increase the bioavailability and the targeted accumulation of drugs in the liver, so as to significantly improve the therapeutic effect of ALI. Curcumin derivative COP-22 exhibits low cytotoxicity and effective anti-inflammatory activity; however, it has poor water solubility. In this study, COP-22-loaded bovine serum albumin (BSA) nanoparticles (22 NPs) were prepared and characterized. They exhibit effective hepatoprotective effects by inhibiting inflammation, oxidative stress, and apoptosis on Lipopolysaccharide/D-Galactosamine-induced acute liver injury of mice. The anti-inflammatory activity of 22 NPs is related to the regulation of the NF-κB signaling pathways; the antioxidant activity is related to the regulation of the Nrf2 signaling pathways; and the apoptosis activity is related to mitochondrial pathways, involving Bcl-2 family and Caspase-3 protein. These three cellular pathways are interrelated and affected each other. Moreover, 22 NPs could be passively targeted to accumulate in the liver through the retention effect and are more easily absorbed than 22.HCl salt in the liver.