Background and Aims
Apolipoprotein A‐1 (ApoA‐1), the major apolipoprotein of high‐density lipoprotein, plays anti‐atherogenic role in cardiovascular diseases and exerts anti‐inflammation effect in ...various inflammatory and infectious diseases. However, the role and mechanism of ApoA‐1 in hepatic ischaemia–reperfusion (I/R) injury is unknown.
Methods
In this study, we measured ApoA‐1 expression in human liver grafts after transplantation. Mice partial hepatic I/R injury model was made in ApoA‐1 knockout mice, ApoA‐1 mimetic peptide D‐4F treatment mice and corresponding control mice to examine the effect of ApoA‐1 on liver damage, inflammation response and cell death. Primary hepatocytes and macrophages were isolated for in vitro study.
Results
The results showed that ApoA‐1 expression was down‐regulated in human liver grafts after transplantation and mice livers subjected to hepatic I/R injury. ApoA‐1 deficiency aggravated liver damage and inflammation response induced by hepatic I/R injury. Interestingly, we found that ApoA‐1 deficiency increased pyroptosis instead of apoptosis during acute phase of hepatic I/R injury, which mainly occurred in macrophages rather than hepatocytes. The inhibition of pyroptosis compensated for the adverse impact of ApoA‐1 deficiency. Furthermore, the up‐regulated pyroptosis process was testified to be mediated by ApoA‐1 through TLR4–NF‐κB pathway and TLR4 inhibition significantly improved hepatic I/R injury. In addition, we confirmed that D‐4F ameliorated hepatic I/R injury.
Conclusions
Our study has identified the protective role of ApoA‐1 in hepatic I/R injury through inhibiting pyroptosis in macrophages via TLR4–NF‐κB pathway. The effect of ApoA‐1 may provide a novel therapeutic approach for hepatic I/R injury.
Compared with the well‐known anion‐templated effects in shaping silver thiolate clusters, the influence from the organic ligands in the outer shell is still poorly understood. Herein, three new ...benzoate‐functionalized high‐nuclearity silver(I) thiolate clusters are isolated and characterized for the first time in the presence of diverse anion templates such as S2−, α‐Mo5O186−, and MoO42−. Single‐crystal X‐ray analysis reveals that the nuclearities of the three silver clusters (SD/Ag28, SD/Ag29, SD/Ag30) vary from 32 to 38 to 78 with co‐capped tBuS− and benzoate ligands on the surface. SD/Ag28 is a turtle‐like cluster comprising a Ag29 shell caging a Ag3S3 trigon in the center, whereas SD/Ag29 is a prolate Ag38 sphere templated by the α‐Mo5O186− anion. Upon changing from benzoate to methoxyl‐substituted benzoate, SD/Ag30 is isolated as a very complicated core–shell spherical cluster composed of a Ag57 shell and a vase‐like Ag21S13 core. Four MoO42− anions are arranged in a supertetrahedron and located in the interstice between the core and shell. Introduction of the bulky benzoate changes elaborately the nuclearity and arrangements of silver polygons on the shell of silver clusters, which is exemplified by comparing SD/Ag28 and a known similar silver thiolate cluster. The three new clusters emit luminescence in the near‐infrared (NIR) region and show different thermochromic luminescence properties. This work presents a flexible approach to synthetic studies of high‐nuclearity silver clusters decorated by different benzoates, and structural modulations are also achieved.
Cluster structures: Three new benzoate‐functionalized high‐nuclearity silver(I) thiolate clusters are isolated and characterized for the first time in the presence of diverse anion templates such as S2−, α‐Mo5O186−, and MoO42−. The benzoate‐type auxiliary ligands play an important role in shaping the Ag‐thiolate clusters (see figure).
Chronic wound infections resulting from severe bacterial invasion have become a major medical threat worldwide. Herein, we report a large‐area, homogeneous, and self‐standing porphyrin‐covalent ...organic framework (COF)‐based membrane with encapsulated ibuprofen (IBU) via an in situ interfacial polymerization and impregnation approach. The obtained IBU@DhaTph‐membrane exhibits highly effective antibacterial and anti‐inflammatory effects via synergistic light‐induced singlet oxygen (1O2) generation and controllable IBU release, which is well supported by in vitro experiments. In addition, the IBU@DhaTph‐membrane‐based biocompatible “band‐aid” type dressing is fabricated, and its excellent anti‐infection and tissue remodeling activities are fully evidenced by in vivo chronic wound‐healing experiments. This study may inspire and promote the fabrication of many more new types of COF‐based multifunctional biomaterials for various skin injuries in clinical medicine.
An ibuprofen‐loaded porphyrin‐COF‐based biocompatible and non‐toxic “band‐aid” type dressing is fabricated, and its excellent synergistic photodynamic antibacterial and controllable drug anti‐inflammatory effects are fully evidenced by in vitro and in vivo bacteria‐infected chronic wound‐healing experiments.
Despite the excellent photodynamic and photothermal properties of organic molecular photosensitizers (PSs) and photothermal agents (PTAs), such as porphyrin and naphthalocyanine, their poor water ...solubility severely impedes their biological applications. Covalent organic frameworks (COFs), as an emerging class of organic crystalline porous materials, possess free active end groups (bonding defects) and large inner pores, which make them an ideal type of nanocarriers for loading hydrophobic organic molecular PSs and PTAs by both bonding defect functionalization (BDF) and guest encapsulation approaches to obtain multifunctional nanomedicines for PDT/PTT combination therapy. In this work, we report a nanoscale COF (NCOF) prepared via a facile synthetic approach under ambient conditions. Furthermore, a dual-modal PDT/PTT therapeutic nanoagent, VONc@COF-Por (3), is successfully fabricated by stepwise BDF and guest encapsulation processes. The covalently grafted porphyrinic PS (Por) and the noncovalently loaded naphthalocyanine PTA (VONc) are independently responsible for the PDT and PTT functionalities of the nanoagent. Upon visible (red LED) and NIR (808 nm laser) irradiation, VONc@COF-Por (3) displayed high 1O2 generation and photothermal conversion ability (55.9%), consequently providing an excellent combined PDT/PTT therapeutic effect on inhibiting MCF-7 tumor cell proliferation and metastasis, which was well evidenced by in vitro and in vivo experiments. We believe that the results obtained herein can significantly promote the development of NCOF-based multifunctional nanomedicines for biomedical applications.
Due to the growing global population, reduction in arable land and effects of climate change, incongruity between food supply and demand has become increasingly severe. Nowadays, with awareness of ...the elementary nutrients required for human growth, increasing attention is being paid to the health and medical functions of food. Along with increased food production achieved by modern agricultural techniques, underutilised functional foods are an important strategy for solving food security problems and maintaining the nutritional quality of the human diet. Rosa roxburghii Tratt (RRT) is a natural fruit that contains unique functional and nutritional constituents, which are characterised by a high anti-oxidant potential. This review summarises the biological characteristics, chemical composition, health-promoting properties and development status of RRT products to inspire investigations on the use of RRT fruit as a functional food, dietary supplement and pharmaceutical additive. The nutrients and functional ingredients of RRT fruit are described in detail to provide more reference information for nutritionists and pharmacists.
Heavy metal accumulation in soil has been rapidly increased due to various natural processes and anthropogenic (industrial) activities. As heavy metals are non-biodegradable, they persist in the ...environment, have potential to enter the food chain through crop plants, and eventually may accumulate in the human body through biomagnification. Owing to their toxic nature, heavy metal contamination has posed a serious threat to human health and the ecosystem. Therefore, remediation of land contamination is of paramount importance. Phytoremediation is an eco-friendly approach that could be a successful mitigation measure to revegetate heavy metal-polluted soil in a cost-effective way. To improve the efficiency of phytoremediation, a better understanding of the mechanisms underlying heavy metal accumulation and tolerance in plant is indispensable. In this review, we describe the mechanisms of how heavy metals are taken up, translocated, and detoxified in plants. We focus on the strategies applied to improve the efficiency of phytostabilization and phytoextraction, including the application of genetic engineering, microbe-assisted and chelate-assisted approaches.
Amino acids are known regulators of cellular signaling and physiology, but how they are sensed intracellularly is not fully understood. Herein, we report that each aminoacyl-tRNA synthetase (ARS) ...senses its cognate amino acid sufficiency through catalyzing the formation of lysine aminoacylation (K-AA) on its specific substrate proteins. At physiologic levels, amino acids promote ARSs bound to their substrates and form K-AAs on the ɛ-amine of lysines in their substrates by producing reactive aminoacyl adenylates. The K-AA marks can be removed by deacetylases, such as SIRT1 and SIRT3, employing the same mechanism as that involved in deacetylation. These dynamically regulated K-AAs transduce signals of their respective amino acids. Reversible leucylation on ras-related GTP-binding protein A/B regulates activity of the mammalian target of rapamycin complex 1. Glutaminylation on apoptosis signal-regulating kinase 1 suppresses apoptosis. We discovered non-canonical functions of ARSs and revealed systematic and functional amino acid sensing and signal transduction networks.
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•Amino acids modify ɛ-amines of lysines•Each tRNA synthetase is the aminoacyl transferase of its cognate amino acid•Aminoacylations can be reversed by deacetylases•Aminoacylations transmit amino acid signals to regulate cellular functions
He et al. reveal that tRNA synthetases sense sufficiency of amino acids and act as aminoacyl transferases to modify ɛ-amines of lysines in proteins, with leucylation of RagA/B regulating mTORC1 activity and glutaminylation of ASK1 inhibiting apoptosis. Lysine aminoacylation marks are removed by SIRT1 and SIRT3.
It is desirable but challenging to design noble-metal-free photocatalysts with improved activity for hydrogen (H2) evolution. In this study, we fabricated hollow hexagonal porous micro-rods assembled ...from core–shell In2O3@carbon nanoparticles (PHIC) via one-step thermal decomposition of the In-MIL-68 precursor. Under simulated sun-light illumination, the final H2 yield rate of PHIC is comparable to that of Pt/PHI (PHI, hollow hexagonal micro-rods assembled from In2O3 nanoparticles without a carbon layer), indicating that the continuous carbon layer coating on In2O3 nanoparticles has a Pt-like effect on improving the photocatalytic activity. Our experimental results indicated that the improved photocatalytic H2 evolution of PHIC is attributed to the synergistic effect of efficient separation of photo-generated electron–hole pairs caused by the coating carbon layer, the enhanced optical absorption of the hollow structure, and the improved accessibility provided by the porous structure. Among them, efficient separation of photo-generated electron–hole pairs plays the main role. Furthermore, we reveal the microscopic charge carrier migration path via In2O3/graphite interfaces, meaning that the photo-generated electrons from In2O3 O2p orbitals transfer into the carbon C2p orbitals, leaving the photo-generated holes in In2O3 O2p orbitals, which is beneficial to improve the separation of photo-generated electron–hole pairs.
To evaluate induction chemotherapy with docetaxel, cisplatin, and fluorouracil (TPF) followed by surgery and postoperative radiotherapy versus up-front surgery and postoperative radiotherapy in ...patients with locally advanced resectable oral squamous cell carcinoma (OSCC).
A prospective open-label phase III trial was conducted. Eligibility criteria included untreated stage III or IVA locally advanced resectable OSCC. Patients received two cycles of TPF induction chemotherapy (docetaxel 75 mg/m(2) on day 1, cisplatin 75 mg/m(2) on day 1, and fluorouracil 750 mg/m(2) on days 1 to 5) followed by radical surgery and postoperative radiotherapy (54 to 66 Gy) versus up-front radical surgery and postoperative radiotherapy. The primary end point was overall survival (OS). Secondary end points included local control and safety.
Of the 256 patients enrolled onto this trial, 222 completed the full treatment protocol. There were no unexpected toxicities, and induction chemotherapy did not increase perioperative morbidity. The clinical response rate to induction chemotherapy was 80.6%. After a median follow-up of 30 months, there was no significant difference in OS (hazard ratio HR, 0.977; 95% CI, 0.634 to 1.507; P = .918) or disease-free survival (HR, 0.974; 95% CI, 0.654 to 1.45; P = .897) between patients treated with and without TPF induction. Patients in the induction chemotherapy arm with a clinical response or favorable pathologic response (≤ 10% viable tumor cells) had superior OS and locoregional and distant control.
Our study failed to demonstrate that TPF induction chemotherapy improves survival compared with up-front surgery in patients with resectable stage III or IVA OSCC.
•Ellagic acid was efficiently extracted from waste chestnut shell by DESs.•Improved recovery of ellagic acid with denaturation of DESs was proposed.•High purity ellagic acid (85.6%) was obtained in ...one step, vs ethanol extraction (36.4%).•Waste chestnut shell can be used directly as a source of ellagic acid.
Chestnut shells in large amounts are significantly underutilized agricultural and forestry waste that can be exploited as a resource for the production of high-valued nature active compounds. In this study, an efficient and green approach was established to extract and recover the highly valued phenolic compound, ellagic acid, from waste chestnut shells with choline chloride-based deep eutectic solvents (DESs). By utilizing optimized ultrasonic-assisted extraction conditions with choline chloride/n-propanol DES, solid–liquid ratio of 40 mg/mL, extraction time of 70 min and extraction power of 200 W, highly efficient extraction value for ellagic acid of 4.64 mg/g was obtained. Meanwhile, ellagic acid was recovered easily with a recovery percentage of 94.9% by anti-solvent precipitation method through the denaturation of DES with water. The purity of ellagic acid in the extracts reached 85.6%, which is more than two times to that via ethanol extraction methods (36.4%). In addition, the recovered ellagic acid exhibited strong antioxidant activity with IC50 (0.309 mg/mL) and significant antibacterial activity with Minimal inhibitory concentration (MIC) (250 mm) and diameter of inhibition zone (DIZ) (17.60 μg/mL). The anti-solvent precipitation method could denature DES, led to higher extraction and recovery efficiency and high-purity ellagic acid simultaneously in one step. The novel method is of great significance to the whole chestnut production process for the utilization of waste chestnut shells. Furthermore, this method can also be used as a green, pollution-free alternative method for the extraction and recovery of phenolic components from natural resources for pharmaceutical and biochemical applications.
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