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Monitoring of glutathione has attracted considerable attention owing to its biological and clinical significance. An eco-friendly, economic, simple, biocompatible probe with excellent sensitivity and selectivity is very important. Herein, FeOOH QD@ATP-BODIPY nanocomposite was fabricated from one-step synthesized FeOOH quantum dots (FeOOH QD) and commercial boron-dipyrromethene-conjugated adenosine 5'-triphosphate (ATP-BODIPY) for glutathione (GSH) sensing in solutions and living cells. Three fascinate merits of FeOOH QD were confirmed: (a) as fluorescence quencher for ATP-BODIPY, (b) as selective recognizer of GSH and (c) with carrier effects and membrane permeability. The construction and response mechanism of the nanocomposite was based on the competitive coordination chemistry and redox reaction of FeOOH QD between GSH and phosphate group of ATP-BODIPY. Under the optimal conditions, the detection limit for GSH was as low as 68.8 nM. Excellent linear range of 0.2-400 μM was obtained. Furthermore, the chemical response of the nanocomposite exhibits high selectivity toward GSH over other electrolytes and biomolecules. It was successfully applied for GSH determination in human serum samples. The MTT assay exhibited FeOOH QD@ATP-BODIPY nanocomposite own good biocompatibility. FeOOH QD@ATP-BODIPY respond to GSH in living cells in situ was also proved via fluorescence imaging. These suggested that the FeOOH QD@ATP-BODIPY nanocomposite had potential application in biological and clinical applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Specific staining of cancer cells is momentous for cancer research. Nanoprobe with multivalent recognition is emerging as powerful tools for bioimaging, but the nonspecific cell uptake and complex functional modification procedures are still obstacles for specific detection and convenient synthesis. Carbon dots (CDs) with an intrinsic targeting ability, excellent optical properties and biocompatibility acquired from an efficient one-step fabrication procedure were urgently desired in specific cancer cells visualization. Herein, inspired by the interrelationships between interface and biomolecular mechanisms, we suggested that it was possible to construct CDs with the desired characteristics for folate receptor (FR) positive-expressed cancer cell imaging via rich hydroxyl groups Tris-assisted one-step hydrothermal treatment of folate acid (FA) and l-Arginine (L-Arg) precursors. The prepared small-sized F-CDs were equipped with abundant hydroxyl, pterin and negative charge surface, and possessed environmental friendliness, outstanding photostability and biocompatibility. Moreover, F-CDs had an intrinsic FR positive-expressed cancer cell targeting ability without any post-modification of the ligands. Rich hydroxyl groups play a vital role in endowing the optical properties and biological effects of F-CDs. F-CDs could be used as a promising candidate for FR-expressed cancer cell labeling and tracking. In addition, the caveolae-mediated endocytosis pathway of F-CDs was ascertained. More importantly, experimental results confirmed that the combination of physicochemical properties may provide an efficient strategy to overcome non-specific cell uptake interactions for cell labeling. Our strategy put forward a promising alternative to design fluorescent CDs for extensive chemical and biomedical applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Cotton fiber holds immense importance as the primary raw material for the textile industry. Consequently, comprehending the regulatory mechanisms governing fiber development is pivotal for enhancing fiber quality. Our study aimed to construct a regulatory network of competing endogenous RNAs (ceRNAs) and assess the impact of non-coding RNAs on gene expression throughout fiber development. Through whole transcriptome data analysis, we identified differentially expressed genes (DEGs) regulated by non-coding RNA (ncRNA) that were predominantly enriched in phenylpropanoid biosynthesis and the fatty acid elongation pathway. This analysis involved two contrasting phenotypic materials (J02-508 and ZRI015) at five stages of fiber development. Additionally, we conducted a detailed analysis of genes involved in fatty acid elongation, including KCS, KCR, HACD, ECR, and ACOT, to unveil the factors contributing to the variation in fatty acid elongation between J02-508 and ZRI015. Through the integration of histochemical GUS staining, dual luciferase assay experiments, and correlation analysis of expression levels during fiber development stages for lncRNA MSTRG.44818.23 (MST23) and GhKCR2, we elucidated that MST23 positively regulates GhKCR2 expression in the fatty acid elongation pathway. This identification provides valuable insights into the molecular mechanisms underlying fiber development, emphasizing the intricate interplay between non-coding RNAs and protein-coding genes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Mild cognitive impairment (MCI) is a significant precursor to dementia, highlighting the critical need for early identification of individuals at high risk of MCI to prevent cognitive decline. The study aimed to investigate the changes in brain structure and function before the onset of MCI. This study enrolled 19 older adults with progressive normal cognition (pNC) to MCI and 19 older adults with stable normal cognition (sNC). The gray matter (GM) volume and functional connectivity (FC) were estimated via magnetic resonance imaging during their normal cognition state 3 years prior. Additionally, spatial associations between FC maps and neurochemical profiles were examined using JuSpace. Compared to the sNC group, the pNC group showed decreased volume in the left hippocampus and left amygdala. The significantly positive correlation was observed between the GM volume of the left hippocampus and the MMSE scores after 3 years in pNC group. Besides, it showed that the pNC group had increased FC between the left hippocampus and the anterior-posterior cingulate gyrus, which was significantly correlated with the spatial distribution of dopamine D2 and noradrenaline transporter. Taken together, the study identified the abnormal brain characteristics before the onset of MCI, which might provide insight into clinical research., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Nanoplastics are an emerging environmental contaminant that can penetrate biological barriers to enter the bloodstream and risk human health. In this context, nanoplastics are likely to interact with proteins in the blood to possibly affect protein structure and function and consequently induce biological effects. Here we report that polystyrene (PS), PS-NH 2 , and PS-COOH nanoplastics disrupt the structure of human fibrinogen (HF) in a dose-dependent manner, as revealed by UV-vis and fluorescence spectroscopy. All three nanoplastics interacted with HF in a similar way, with PS-NH 2 having the greatest effect on HF structure. Furthermore, fibrinogen polymerization experiments demonstrated that nanoplastics have the potential to promote blood coagulation, with PS-NH 2 again having a stronger effect. Collectively, these results provide insights into the interactions occurring between nanoplastics and HF, the likely transport and fate of nanoplastics in organisms, and their potential pathophysiological consequences., Competing Interests: Declaration of competing interest All authors declare no conflict of interest., (Copyright © 2023. Published by Elsevier B.V.)

Nanoplastics are the persistent pollutants in a variety of environments, representing a potential threat to human health. Notably, plastic particles have been detected in sample of human bloodstream. It is thus significant to investigate the effects of nanoplastics on the cardiovascular system owing to its ease transfer through the bloodstream to other organs. However, few studies have been performed to evaluate the cardiovascular toxicity of nanoplastics. Herein, we pursued to investigate the adverse cardiovascular impacts of polystyrene (PS), PS-NH 2 and PS-COOH nanoplastics on mice. Experimental results demonstrated that the exposure to these nanoplastics could result in structural damage of vascular endothelial cells and inflammatory response. Moreover, it was found out that the dysfunctions of coagulation and prethrombotic state were caused by nanoplastics, which could be ascribed to the activation of JAK1/STAT3/TF signaling pathway. In summary, results clearly indicated that nanoplastic exposure lead to vascular toxicity to mice, which serves as a basis for future studies about the potential physiological threat of nanoplastics to humans., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

Microbiologically induced calcite precipitation (MICP) technology shows potential for remediating heavy metal pollution; however, the underlying mechanism of heavy metal mineralization is not well-understood, limiting the application of this technology. In this study, we targeted Cd contamination (using 15:1, 25:1, and 50:1 Ca 2+ /Cd 2+ molar ratios) and showed that the ureolytic bacteria Sporosarcina ureilytica ML-2 removed >99.7 % Cd 2+ with a maximum fixation capacity of 75.61 mg-Cd/g-CaCO 3 and maximum precipitation production capacity of 135.99 mg-CaCO 3 /mg-cells. Quantitative PCR analysis showed that Cd 2+ inhibited the expression of urease genes (ureC, ureE, ureF, and ureG) by 70 % in the ML-2 strain. Additionally, the pseudo-first-order kinetics model (R 2 = 0.9886), intraparticle diffusion model (R 2 = 0.9972), and Temkin isotherm model (R 2 = 0.9828) described the immobilization process of Cd 2+ by bio calcite in MICP-Cd system. The three Cd 2+ mineralization products generated by MICP were attributed to surface precipitation (Cd 2+ → Cd(OH) 2 ), direct binding with the CO 3 2- /substitution calcium site of calcite (Cd 2+ → CdCO 3 , otavite), and calcite lattice vacancy anchors (Cd 2+ → (Ca x Cd 1-x )CO 3 ). Our findings improve the understanding of the mechanisms by which MICP can achieve in situ stabilization of heavy metals., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

Targeting cardiomyocyte plasticity has emerged as a new strategy for promoting heart repair after myocardial infarction. However, the precise mechanistic network underlying heart regeneration is not completely understood. As noncoding RNAs, circular RNAs (circRNAs) play essential roles in regulating cardiac physiology and pathology. The present study aimed to investigate the potential roles of circMdc1 in cardiac repair after injury and elucidate its underlying mechanisms. Here, we identified that circMdc1 levels were upregulated in postnatal mouse hearts but downregulated in the regenerative myocardium. The expression of circMdc1 in cardiomyocytes is sensitive to oxidative stress, which was attenuated by N-acetyl-cysteine. Enforced circMdc1 expression inhibited cardiomyocyte proliferation, while circMdc1 silencing led to cardiomyocyte cell cycle re-entry. In vivo, the cardiac-specific adeno-associated virus-mediated knockdown of circMdc1 promoted cardiac regeneration and heart repair accompanied by improved heart function. Conversely, circMdc1 overexpression blunted the regenerative capacity of neonatal hearts after apex resection. Moreover, circMdc1 was able to block the translation of its host gene Mdc1 specifically by binding to PABP, affecting DNA damage and the chromosome stability of cardiomyocytes. Furthermore, overexpression of Mdc1 caused damaged mouse hearts to regenerate and repair after myocardial infarction in vivo. Oxidative stress-sensitive circMdc1 plays an important role in cardiac regeneration and heart repair after injury by regulating DNA damage and chromosome stability in cardiomyocytes by blocking the translation of the host gene Mdc1., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Aims: N6-Methyladenosine (m 6 A), one of the important epigenitic modifications, is very commom in messenger RNAs (mRNAs) of eukaryotes, and has been involved in various diseases. However, the role of m 6 A modification in heart regeneration after injury remains unclear. The study was conducted to investigate whether targeting methyltransferase-like 3 (METTL3) could replenish the loss of cardiomyocytes (CMs) and improve cardiac function after myocardial infarction (MI)., Methods and Results: METTL3 knockout mouse line was generated. A series of functional experiments were carried out and the molecular mechanism was further explored. We identified that METTL3, a methyltransferase of m6A methylation, is upregulated in mouse hearts after birth, which is the opposite of the changes in CMs proliferation. Furthermore, both METTL3 heterozygous knockout mice and administration of METTL3 shRNA adenovirus in mice exhibited CMs cell cycle re-entered, infract size decreased and cardiac function improved after MI. Mechanically, the silencing of METTL3 promoted CMs proliferation by reducing primary miR-143 (pri-miR-143) m 6 A modificaiton, thereby inhibiting the pri-miR-143 into mature miR-143-3p. Moreover, we found that miR-143-3p has targeting effects on Yap and Ctnnd1 so as to regulate CMs proliferation., Conclusion: METTL3 deficiency contributes to heart regeneration after MI via METTL3-pri-miR-143-(miR-143)-Yap/Ctnnd1 axis. This study provides new insights into the significance of RNA m 6 A modification in heart regeneration., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

It is highly tempting to develop high-efficacy targeted nanotherapeutics based on FDA approved polymers like PLGA. Herein, we describe facile fabrication of robust, hyaluronic acid-surfaced and disulfide-crosslinked star-PLGA nanoparticles (HA-sPLGA XNPs) for targeted and reduction-triggered release of docetaxel (DTX), achieving markedly enhanced treatment of A549 lung tumor in vivo. HA-sPLGA XNPs carrying 5.2 wt.% DTX (DTX-HA-sPLGA XNPs) had a size of 105.5 ± 0.5 nm and great stability while almost completely released DTX under 10 mM glutathione. Confocal and flow cytometry experiments revealed fast cellular uptake of HA-sPLGA XNPs by CD44-overexpressing A549 cells. DTX-HA-sPLGA XNPs held much higher potency to A549 cells than DTX-loaded HA-surfaced and non-crosslinked star-PLGA nanoparticles (DTX-HA-sPLGA NPs), DTX-loaded HA-surfaced and non-crosslinked linear-PLGA nanoparticles (DTX-HA-lPLGA NPs), and free DTX (IC 50  = 0.18 versus 0.38, 1.21 and 0.83 µg DTX equiv./mL). Intriguingly, DTX-HA-sPLGA XNPs revealed a prolonged elimination half-life of 4.18 h and notable accretion of 9.49%ID/g in A549 tumor after 8 h injection. Accordingly, DTX-HA-sPLGA XNPs demonstrated significantly better suppression of subcutaneous A549 lung tumor than DTX-HA-PLGA NPs, DTX-HA-lPLGA NPs, and free DTX controls. HA-sPLGA XNPs with low toxicity and multi-functionality appear to be a unique targeted vehicle for chemotherapy of CD44-overexpressing tumors. STATEMENT OF SIGNIFICANCE: PLGA nanoparticles with superior safety and biodegradability are among the most advanced vehicles for therapeutic delivery. The efficacy of nanomedicines based on PLGA is, however, suboptimal, due to poor tumor cell selectivity and uptake, drug leakage, and slow drug release at the pathological site. It is highly desired to develop functional PLGA nanoparticles to improve their tumor-targeting ability and therapeutic efficacy. The sophisticated fabrication and potential toxicity concerns of reported novel PLGA nanoformulations, nevertheless, preclude their clinical translation. Here, we developed hyaluronic acid-surfaced and disulfide-crosslinked star-PLGA nanoparticles (HA-sPLGA XNPs) that enabled stable encapsulation and targeted delivery of docetaxel (DTX) to CD44+ A549 lung cancer cells in vitro and in vivo, affording markedly improved tumor accumulation and repression and lower side effects compared with free DTX control. Importantly, HA-sPLGA XNPs are based on fully biocompatible materials and comparably simple to fabricate. The evident tumor targetability and safety makes HA-sPLGA XNPs a unique and potentially translatable platform for chemotherapy of CD44+ cancers., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

The effective treatment of hepatocellular carcinoma (HCC) requires development of novel drug formulations that selectively kill HCC cells while sparing healthy liver cells. Here, we designed and investigated HCC-specific peptide, SP94 (SFSIIHTPILPLGGC), decorated smart polymersomal doxorubicin hydrochloride (SP94-PS-DOX) for potent treatment of orthotopic human SMMC-7721 HCC xenografts. SP94-PS-DOX was fabricated by post ligand-modification, affording robust nano-formulations with a diameter of ∼ 76 nm and DOX content of 9.9 wt.%. The internalization of SP94-PS-DOX by SMMC-7721 cells showed a clear dependence on SP94 surface densities, in which 30 % SP94 resulted in ca. 3-fold better cellular uptake over non-targeted control (PS-DOX). In accordance, SP94-PS-DOX exhibited superior inhibition of SMMC-7721 cells to PS-DOX and clinical liposome injections (Lipo-DOX). Notably, a remarkable tumor deposition of 14.9 %ID/g and tumor-to-normal liver ratio of ca. 6.9 was observed for SP94-PS-DOX in subcutaneous SMMC-7721 HCC xenografts. More interestingly, SP94-PS-DOX under 10 mg DOX/kg induced far better therapeutic efficacy toward orthotopic SMMC-7721 HCC models than PS-DOX and Lipo-DOX controls giving substantial survival benefits and little adverse effects. The remarkable specificity and therapeutic outcomes lend SP94-PS-DOX promising for targeted HCC therapy., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Increasing evidences have demonstrated that the reactive oxygen species play important roles in the initiation and progress of LPS-induced kidney injury (KI). The present work investigated the antioxidant, anti-inflammatory and renoprotective effects of acidic spent mushroom compost polysaccharides (ASMCP) by Lentinula edodes against the LPS-induced KI in mice. The results demonstrated that ASMCP showed anti-inflammatory effects on reducing the serum levels of TNF-α, IL-6 and IL-1β, inhibiting the elevation of lipid peroxidation, lowering the serum levels of BUN, CRE and UA, and improving the antioxidant status by enhancing renal enzyme activities (SOD, GSH-Px, CAT and T-AOC). Furthermore, the histological observations of renal cortex and renal medulla also indicated the potential renoprotective effects of ASMCP. These conclusions suggested that ASMCP might be suitable for functional foods and a potentially effective candidate medicine for the treatment of KI., Competing Interests: Declaration of Competing Interest The authors declared that they have no competing interests., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Ribavirin has been proven to be an antiviral treatment, whereas there are still risks of hemolysis and congenital malformation. Abnormal cardiac development contributes to the occurrence and development of many heart diseases. However, there is so far no evidence that ribavirin induces human cardiac developmental toxicity. Herein, we employed the cardiac differentiation model of human induced pluripotent stem cells (hiPSCs) to determine the impact of ribavirin on heart development. Our data showed that ribavirin at clinically high concentrations (5 and 10 μM) significantly inhibited the proliferation and differentiation of hiPSCs from mesoderm to cardiac progenitor cells and cardiac progenitor cells to cardiomyocytes, but not from pluripotent status to mesoderm. Meanwhile, DCFH-DA staining revealed that ribavirin could increase ROS content in the mid-phase of differentiation. In addition, ribavirin treatment (1, 5 and 10 μM) remarkably caused DNA damage which was shown by the increase of γH2AX-positive cells and upregulation of the p53 during the differentiation of hiPSCs from mesoderm to cardiac progenitor cells. Moreover, exposuring to ribavirin (5 and 10 μM) markedly upregulated the expression of lncRNAs Gas5 in both mid-phase and late phase of differentiation and HBL1 in the mid-phase. In conclusion, our results suggest that ribavirin is detrimental in cardiac differentiation of hiPSCs, which may be associated with DNA damage, upregulated p53 and increased Gas5. It may provide the evidence for the rational clinical application of ribavirin., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The present work aimed to investigate the antioxidation, hepatic- and renal-protection of water-extractable polysaccharides (WPS) by Dictyophora indusiata fruiting body on high-fat emulsion-induced obese mice. The structural analysis indicated that WPS was the α-configurational heteropolysaccharide with the major monosaccharides of mannose and glucose, and the polydispersity of 1.77. The in vivo results showed that WPS administration could improve obesity-associated hepatic and renal metabolic impairment, reduce body weight and ameliorate oxidative stress of liver and kidney by down-regulating serum enzyme activities and hepatic lipid levels, stabilizing serum lipid status, enhancing antioxidant abilities and decreasing insulin and leptin resistance. The in vitro experiments showed that WPS had potential abilities to scavenge free radicals. The conclusions demonstrated that WPS might be used as a salutary food and natural medicine for preventing obesity-associated damage and its complications., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Arsenic trioxide (ATO) has been recommended as the first-line agent for the treatment of acute promyelocytic leukaemia (APL), due to its substantial anticancer effect. Numerous clinical reports have indicated that ATO is a developmental toxicant which can result in birth defects of human beings. But whether arsenic trioxide can lead to human cardiac developmental toxicity remains largely unknown. So the present study aims to explore the influence and mechanisms of ATO on human cardiac development by using a vitro cardiac differentiation model of human induced pluripotent stem cells (hiPSCs). Here we found that clinically achievable concentrations (0.1, 0.5 and 1 μM) of ATO resulted in a significant inhibition of proliferation during the whole process of cardiac differentiation of hiPSCs. Meanwhile, TUNEL assay revealed that ATO could cause cell apoptosis during cardiac differentiation in a concentration-dependent manner. Consistently, we found that ATO reduced the expressions of mesoderm markers Brachyury and EOMES, cardiac progenitor cell markers GATA-4, MESP-1 and TBX-5, and cardiac specific marker α-actinin in differentiated hiPSCs. Furthermore, ATO treatment had caused DNA damage which was shown in the upregulation of γH2AX, a sensitive marker for DNA double-strand breaks. Taken together, ATO blocked cardiomyocyte differentiation, induced apoptosis and cell growth arrest during cardiac differentiation of hiPSCs, which might be associated with DNA damage., (Copyright © 2019 Elsevier B.V. All rights reserved.)

In the present work, we investigated the anti-hyperlipidemic, antioxidant and organic protection effects of acidic-extractable Dictyophora indusiata polysaccharides (Ac-DPS) on hyperlipidemic mice induced by high-fat emulsion. The results demonstrated that Ac-DPS had impressive abilities to mitigate oxidative stress by increasing the activities of antioxidant enzyme and reducing the contents of lipid peroxide. Moreover, lipid levels in serum were returned to normal status. Besides, Ac-DPS exhibited potential hepatic and renal protection effects reflected by decreasing serum enzyme activities, lowering TBIL, UREA and CREA levels and increasing ALB content. At the same time, histopathological observations proved protective effects of Ac-DPS on organs. Subsequently, the physical properties of polysaccharide were also investigated by HPGPC and FT-IR. The above consequences confirmed the important role of Ac-DPS as a functional food and natural medicine in the fight against oxidative stress and the prevention of hyperlipidemia., (Copyright © 2019. Published by Elsevier B.V.)

The aims of this work were to extract the enzymatic residue polysaccharides (EnRPS) from Pleurotus ostreatus and investigate the antioxidant and anti-hyperlipidemic effects on high-fat-high-cholesterol emulsion (HFHCE)-induced liver injured mice. The results revealed that EnRPS at 400 mg/kg bw showed superior liver protective effects by ameliorating the AI, lowing the hepatic MPO, FFA, ADPN, TC and TG indicators, and improving the antioxidant status by enhancing liver enzyme activities (SOD, CAT, LEP, INS and T-AOC), eliminating the MDA content, decreasing the levels of LDL-C, TC, TG, ALT, AST and ALP, and increasing the HDL-C in serum. And in addition, GC, FTIR, NMR and pathological sections were also studied. The above consequences suggested that EnRPS could be used as functional foods of oxidative stress and anti-hyperlipidemic against liver injury., (Copyright © 2019. Published by Elsevier B.V.)

With the world's largest population at 1.3 billion and a rising number of foreigners, China requires physicians and a healthcare system that meets the needs of a large and diverse population. Along with rapid economic and technological advancements, the Medical Administration Division of the National Health and Family Planning Commission remarked that medical services through online appointments and payments have improved its efficacy over the past 2 years. According to the official report from the National Health and Family Planning Commission of the People's Republic of China website, China has so far established a total of 25,000 hospitals and 981,000 community health centers, that includes 17,100 dermatologists and 190,000 residents in training., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Bortezomib (BTZ) provides one of the best treatments for multiple myeloma (MM). The efficacy of BTZ is, nevertheless, restricted by its fast clearance, low selectivity, and dose limiting toxicities. Here, we report on targeted BTZ therapy of MM in vivo by hyaluronic acid-shelled and core-disulfide-crosslinked biodegradable micelles (HA-CCMs) encapsulating lipophilized BTZ, bortezomib-pinanediol (BP). HA-CCMs loaded with 7.3 BTZ equiv. wt% exhibited a small size of 78 nm, good stability in 10% FBS, and glutathione-triggered drug release. MTT assays in CD44 positive LP-1 multiple myeloma cells revealed that BP encapsulated in HA-CCMs caused enhanced antiproliferative effect compared with free BP. Flow cytometry, confocal microscopy and MTT assays indicated BP-loaded HA-CCMs (HA-CCMs-BP) could actively target to LP-1 cells and induce high antitumor effect. Proteasome activity assays in vitro showed HA-CCMs-BP had a similar proteasome activity inhibition as compared to free BTZ at 18 h. The fluorescence imaging using Cy5-labeled HA-CCMs showed that HA-CCMs had a long elimination half-life and enhanced tumor accumulation via HA-mediated uptake mechanism. The therapeutic studies in LP-1 MM-bearing mice revealed better treatment efficacy of HA-CCMs-BP compared with free BTZ, in which HA-CCMs-BP at 3 mg BTZ equiv./kg brought about significant tumor growth inhibition and survival benefits. Loading of lipophilized BTZ into HA-shelled multifunctional micelles has emerged as an exciting approach for bortezomib therapy of MM. STATEMENT OF SIGNIFICANCE: Multiple myeloma (MM) is the second most common hematological malignancy. Bortezomib (BTZ), a potent proteasome inhibitor, provides one of the best treatments for MM. The clinical efficacy of BTZ is, however, limited by its quick clearance, poor selectivity, and significant side effects including myelosuppression and peripheral neuropathy. Here, we report on targeted BTZ therapy of MM in vivo by hyaluronic acid-shelled and core-disulfide-crosslinked biodegradable micelles (HA-CCMs) encapsulating lipophilized BTZ, bortezomib-pinanediol (BP). Our results showed that BP-loaded HA-CCMs exhibit markedly enhanced toleration, broadened therapeutic window, and significantly more effective growth suppression of CD44-overexpressed multiple myeloma in nude mice than free bortezomib. Lipophilized BTZ-loaded HA-CCMs has opened a new avenue for targeted bortezomib therapy of multiple myeloma., (Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

In the present study, we investigated the antioxidant and hepatoprotective effects of intracellular mycelium polysaccharides from Pleurotus geesteranus (IMPP) to address acute alcoholic liver diseases (ALD). Animal studies have demonstrated that the hepatic parameters of CYP2E1, MPO, TC, ALT, AST and ALP, HDLC, LDL-C and VLDL-C were improved; the inflammatory factor levels, including TNF-α, IL-1β and IL-6, were decreased; the hepatic ADH and ALDH activities were inhibited; the activities of the antioxidant enzymes SOD, GSH-Px, CAT and T-AOC were enhanced; and the MDA and LPO contents were reduced by IMPP treatment. Furthermore, the liver histopathology confirmed the beneficial effects of IMPP against ALD in mice, demonstrating that IMPP had the potential to remediate alcoholic hepatitis. Besides the properties of typical pyran-type polysaccharides obtained by β-glycosidic bonding rich in fucose, the results demonstrated that IMPP might be used as a functional food and natural medicine for preventing ALD and its complications., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Metal-arene complexes containing bioactive natural-product derived ligands can have new and unusual properties. We report the synthesis, characterization and antiproliferative activity of two new Ru(II) arene complexes with imidazole (dichlorido complex 1) or bipyridyl (chlorido complex 2) ligands conjugated to 18β-glycyrrhetinic acid, an active triterpenoid metabolite of Glycyrrhiza glabra. In general, the conjugated ligands and complexes showed only moderate activity against HeLa (cervical), MCF-7 (breast) and A2780 (ovarian) cancer cells, although the activity of complex 2 in the former two cell lines approached that of the drug cisplatin. Complex 2 (in contrast to complex 1) also exhibited significant activity towards both Gram-positive S. aureus and Gram-negative E. coil bacteria. Complex 2 can induce condensation of DNA and enhances the generation of intracellular reactive oxygen species (ROS). The conjugation of natural products to ligands in organometallic half-sandwich complexes provides a strategy to enhance their biological activities., (Copyright © 2018 Elsevier Inc. All rights reserved.)

In our present work, the polysaccharides (MPS) were successfully extracted from the mycelia of Hypsizygus marmoreus, and purpose of our work was to evaluate the analysis of the characterization, anti-inflammation and anti-oxidation against the lung failure induced by lipopolysaccharide (LPS) in mice. Pretreatment with MPS at 800mg/kg markedly ameliorated the lung wet-to-dry weight (W/D) ratio and pulmonary histopathological conditions, reduced the tumor necrosis factor-alpha (TNF)-α, interleukin (IL)-6, and IL-1β levels in bronchoalveolar lavage fluid (BALF), myeloperoxidase (MPO) activities. In addition, the protective effects of MPS might be attributed to the down-regulations of the serum complement 3 (C3), glutamyl transpeptidase (GGT) and high-sensitivity C-reactive protein (hs-CPR) contents, as well as improving the antioxidant status by enhancing pulmonary enzyme activities (catalase (CAT), superoxide dismutase(SOD), glutathione peroxidase (GSH-Px) and total antioxidant capacity (T-AOC)) and eliminating the lipid peroxidation (LPO) and malondialdehyde (MDA), respectively. What's more, our work investigated the characterization of the MPS., (Copyright © 2018. Published by Elsevier B.V.)

In present study, the soluble polysaccharides by enzyme-assisted extraction from Agaricus bisporus (EnAPS) and its purified fractions of EnAPS-1, -2 and -3 were successfully obtained, and the antioxidant activities and anti-aging effects were investigated. The in vitro antioxidant assay demonstrated that EnAPS-2 had superior scavenging activities on DPPH and hydroxyl radicals, chelating activities of Fe 2+ and reducing power. The in vivo animal experiments showed that both EnAPS and its purifies fractions had potential anti-aging effects against the d-galctose-induced aging diseases on liver, kidney, brain and skin, possibly by increasing the antioxidant enzymes, reducing the lipid peroxidation, improving the organ functions and remitting the lipid metabolism. The conclusions demonstrated that the polysaccharides by A. bisporus might be suitable for applying functional foods and natural drugs in preventing and delaying the aging and its complications., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Iridium-based anticancer reagents are receiving increasing attention for their high cytotoxicity. Herein, by activating CH bonds in the well-known antioxidant α-phenyl-N-tert-butylnitrone (PBN), we synthesized and characterized a series of new iridium complexes. Complex 1-AMP exhibited the best antiproliferation activity towards human ovarian cancer A2780 cells. The azide group in complex 1-AMP underwent the Cu(I)-catalysed azide-alkyne cycloaddition (CuAAC) reaction and the resulting fluorescent imaging in cells suggested it mainly accumulated in mitochondria. In comparison, to eliminate cytotoxicity of Cu(I) catalyst, we conducted a reaction between complex 1-AMP and a commercialized dye via strain-promoted alkyne-azide cycloaddition (SPAAC) reaction in live cells, confirming its targeting mainly in the mitochondria. Iridium-based anticancer complexes containing a nitrone ligand and azide group may offer a useful tool to probe the mechanism of metallodrugs., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

In present study, two hydrolyzed residue polysaccharides (RPS) of enzymatic-RPS (ERPS) and acidic-RPS (ARPS) were successfully obtained from the residue of Lentinula edodes, and the anti-inflammatory as well as antioxidative effects on lipopolysaccharide-induced (LPS-induced) lung injured mice were investigated. The results demonstrated that ERPS showed superior lung protective effects by ameliorating the lung wet-to-dry weight (W/D) ratio, reducing the TNF-α, IL-6, and IL-1β levels in BALF, lowing the pulmonary MPO activity, decreasing the serum C3 and hs-CPR contents, as well as improving the antioxidant status by enhancing pulmonary enzyme activities (SOD, GSH-Px, CAT, and T-AOC) and eliminating the lipid peroxidation (MDA and LPO), respectively. These conclusions indicated that both RPS and its hydrolysates (ARPS and ERPS) might be suitable for functional foods and a potentially effective candidate medicine for the treatment of lung injury., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Two extractable polysaccharides of Ac-MPS and Al-MPS were extracted from the mycelium of Agrocybe aegerita (Brig.) Sing and the in vitro antioxidant activities and in vivo anti-aging activities in a d-gal-induced aging mice were investigated in the present study. The in vitro antioxidant analysis showed that Ac-MPS showed superior scavenging effects on hydroxyl of 68.62±2.59% and DPPH of 85.19±3.26% at the concentration of 4500μg/mL. Biochemical indices and antioxidant analysis in vivo showed that Ac-MPS had better effects in raising hepatic activities of SOD, CAT, GPx and T-AOC, inhibiting hepatic contents of LPO and MDA, as well as improving serum lipid levels of LDL-C, HDL-C, LDL-C/HDL-C, TG and TC. Furthermore, HYP measurements suggested that skin collagen in aging mice could be maintained. This study suggested that both Ac-MPS and Al-MPS could be used as potential natural agents or dietary supplements in attenuating aging and its complications., (Copyright © 2017 Elsevier B.V. All rights reserved.)

This study was designed to investigate the antioxidant and anti-aging effects of D-galatose-induced (D-gal-induced) aging mice as well as monosaccharide compositions of acidic-extractable polysaccharides (AcAPS) and its major purified fractions (AcAPS-1, AcAPS-2 and AcAPS-3) from the fruiting body of Agaricus bisporus. In the in vitro assays, AcAPS-2 showed superior scavenging activities on hydroxyl (82.98±4.67%) and DPPH (64.47±4.05%) radicals at the concentration of 1.0mg/mL than AcAPS and other polysaccharides fractions. For in vivo anti-aging analysis, AcAPS-2 showed superior effects on hepatic and nephric protection by improving serum enzyme activities, biochemical levels, lipid contents and antioxidant status, respectively. The monosaccharide analysis showed that rhamnose (Rha) and glucose (Glu) may play vital roles in maintaining the antioxidant and anti-aging activities. The results suggested that both AcAPS and its purified fractions might be suitable for functional foods and natural drugs in preventing the acute aging-associated diseases., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The present work was designed to investigated the antioxidant, anti-inflammation, and pulmonary protective effects of SMPS and MPS from Oudemansiella radicata on LPS-induced lung injured mice. The results demonstrated that SMPS showed potential effects on relieving lung injury and preventing oxidative stress, reflecting by decreasing the serum levels of C3, CRP and GGT, increasing the pulmonary activities of SOD, GSH-Px, CAT and T-AOC, as well as down-regulating the MDA and LPO contents, respectively. Furthermore, the levels of TNF-α (224.211±3.12ng/mL), IL-1β (254.557±2.18ng/L), and IL-6 (18.214±0.15ng/L) in BALF of mice treated with SMPS at the dosage of 400mg/kg/d significantly lower than that in the lung injured mice. These conclusions indicated that both SMPS and MPS possessed potent antioxidants and anti-inflammation activities, and could be used as functional foods and natural drugs in preventing lung injury., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The in vitro antioxidant and in vivo anti-aging activities in D-galactose-induced aging mice of exopolysaccharides (EPS) and its fractions (EPS-1, EPS-2 and EPS-3) by Agrocybe cylindraceas were investigated presently. The scavenging effects of EPS-2 on hydroxyl (HO) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals were 97.1±4.25% and 90.23±3.25%, while the reducing power reached 1.18±0.08 at 120mg/L, which were higher than EPS, EPS-1 and EPS-3 at 1000mg/L. The EPS showed potential anti-aging activities via reducing the contents of malonaldehyde (MDA) and total cholesterol (TC), as well as increasing the activities of superoxide dismutase (SOD) activities, glutathione peroxidase (GSH-Px) activities, and total antioxidant capacity (T-AOC). Additionally, the monosaccharide analysis showed EPS contained rhamnose and glucose with the molar ratio of 2.8:1. These results demonstrated that EPS could be used as functional foods and natural drugs on preventing and mitigating the aging process., (Copyright © 2017 Elsevier B.V. All rights reserved.)

In present study, a quadratic regression model based on the response surface methodology (RSM) coupled with Box-Behnken design (BBD) was employed to optimize the enzyme-assisted extraction (EAE) process of enzymatic-extractable Pleurotus djamor polysaccharides (EnPPs). By solving the regression equations and analyzing the model graphs, the optimum conditions were at pH 7.36, water to material ratio 56.78, extraction time 44.77min and extraction temperature 35.36°C, respectively. Under these conditions, the experimental yields of EnPPs reached 3.61%, which were in good agreement with the validated values (3.57±0.51%). Basic physicochemical properties including molecular weights, structural identification by FT-IR and monosaccharide compositions were processed. In addition, the in vivo inhibiting activities against oxidative stress were investigated. The results provided an alternative bioresource for the exploitation of EnPPs under EAE from P. djamor, and the EnPPs had potential effects in prevention of oxidative stress., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Psoriasis is a high-incident T-cell-mediated autoimmune disease mainly affecting the skin. Interleukin (IL)-27 is a novel member of the IL-6/IL-12 cytokine family, which plays a versatile role in the differentiation and function of distinct T cell subsets. Previous studies uncovered that IL-27 promoted the onset of psoriasis through enhancing the differentiation of T helper (Th) 1 cells. However, the role of IL-27 in other psoriasis-related Th lineages, especially Th17 cells, remains elusive., Objects: The study aimed to investigate the role of IL-27 in the progression of psoriasis and its underlying mechanisms, particularly its influence on Th1 and Th17., Methods: IL-27 and IL-27 receptor α (IL-27Rα) expressions in normal and lesional skin were determined by immunohistochemistry and western blot analysis. Serum levels of IL-27 and IL-10 were measured by ELISA. Expression levels of IL-27 and IL-27 receptor (IL-27R) mRNA in the skin tissue and peripheral blood mononuclear cells (PBMC) were assessed by quantitative polymerase chain reaction (PCR) analysis. To explore the function of IL-27 in vivo, we used imiquimod (IMQ)-induced psoriasis mouse model. We treated mice with IL-27 or its antagonist, evaluated disease severity and detected the cytokine secretion from splenic CD4+ T cells by flow cytometric analysis and the expression levels of IL-17 and IFN-γ in serum and skin lesion., Results: The expression levels of IL-27 and IL-27Rα were significantly reduced in the moderate-to-severe psoriatic lesions, along with a consistent decrease in serum IL-27 levels, compared with those of healthy control subjects. Moreover, subcutaneous administration of IL-27 recombinant protein lessened severity of IMQ-induced psoriasis-like cutaneous lesions, whereas IL-27p28 antagonist exaggerated the disease severity. Further analysis revealed that IL-27 significantly repressed IL-17 secretion from CD4+ T lymphocytes. Also administration of IL-27 decreased IL-17A level while IL-27p28 antagonist increased IL-17A level in serum and psoriasis-like lesion in the IMQ-treated mice., Conclusion: Our results suggest that IL-27 might predominantly play a protective role in the pathogenesis of psoriasis through abrogating Th17 differentiation. The potential therapeutic benefit of harnessing IL-27 in treating psoriasis awaits future investigation., (Copyright © 2016 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.)

Background: Impaired dendrite outgrowth of melanocytes is one of the reasons triggering vitiligo. RNASET2 was identified as one of the risk genes for vitiligo in a GWAS study conducted in the Chinese Han population. However, the role of Rnaset2 in the outgrowth of melanocytes is rarely studied., Objective: This study is to investigate the effects of Rnaset2 in regulating the outgrowth of melanocytes and its interacting proteins., Methods: Stress conditions (UV irradiation, hydrogen peroxide, and lipopolysaccharides) were applied to primary human epidermal melanocytes (HEMs) and epidermal keratinocytes (HEKs). HEKs with Rnaset2 overexpression were co-cultured with HEMs. Rnaset2 expression levels were detected by ELISA. HEMs, HEKs and A375 cells were treated with recombinant Rnaset2 protein and actin network was observed with fluorescence microscope. Cell migration assay was performed using nuclepore filters after incubating A375 cells with recombinant Rnaset2 protein. Human proteome microarray was performed to identify proteins interacting with Rnaset2. Co-immunoprecipitation was conducted to verify the results., Results: Our results showed that after exposing to stress conditions, Rnaset2 expression and secretion by HEKs and HEMs were increased. Co-culture of HEKs and HEMs showed that outgrowth of HEMs was inhibited by Rnaset2 overexpression in HEKs. Additionally, human recombinant Rnaset2 protein treatment altered the actin network of HEMs, HEKs and A375 cells. The migration of A375 cells was also inhibited by human recombinant Rnaset2 protein treatment. Human proteome microarray identified shootin1, an important protein involved in axon outgrowth, as one of the interacting proteins of Rnaset2. Co-immunoprecipitation confirmed that Rnaset2 interacted with shootin1 in vitro., Conclusion: Rnaset2 inhibits melanocyte outgrowth through interacting with shootin1 and this effect may be associated with vitiligo pathogenesis. Rnaset2 may be a potential therapeutic target for vitiligo., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)