Preventive effects of lactoferrin on acute alcohol-induced liver injury via iron chelation and regulation of iron metabolism.

Lactoferrin is widely found in milk and has the ability to bind iron. Previous studies have reported that lactoferrin was effective in the prevention and treatment of acute alcohol-induced liver injury (AALI). Ferroptosis is a recently discovered cell death and is involved in the development of AALI. However, the potential role of lactoferrin in acute alcohol-induced ferroptosis is still unclear. In this study, we observed that lactoferrin (10, 20 and 40 µg/mL) significantly mitigated alcohol (300 mM)-induced injury in vitro. Additionally, lactoferrin (100 and 200 mg/kg bw) significantly alleviated alcohol (4.8 g/kg bw)-induced injury in vivo. Our results showed that lactoferrin inhibited alcohol-induced upregulation of the ferroptosis marker protein ACSL4 and downregulation of GPX4. Meanwhile, lactoferrin treatment successfully reversed the elevated Malondialdehyde (MDA) levels and the reduced Glutathione (GSH) levels caused by alcohol treatment. These results can indicate that lactoferrin significantly decreased ferroptosis in vivo and in vitro. Lactoferrin has the potential to chelate iron, and our results showed that lactoferrin (20 µg/mL) significantly reduced iron ions and the expression of Ferritin Heavy Chain (FTH) under FeCl3 (100 µM) treatment. It was demonstrated that lactoferrin had a significant iron-chelating effect and reduced iron overload caused by FeCl3 in AML12 cells. Next, we examined iron content and the expression of iron metabolism marker proteins Transferrin Receptor (TFR), Divalent metal transporter 1 (DMT1), FTH, and Ferroportin (FPN). Our results showed that lactoferrin alleviated iron overload induced by acute alcohol. The expression of TFR and DMT1 was downregulated and FPN and FTH were upregulated after lactoferrin treatment in vivo and in vitro. Above all, the study suggested that lactoferrin can alleviate AALI by mitigating acute alcohol-induced ferroptosis. Lactoferrin may offer new strategies for the prevention or treatment of AALI.

A Double-Layer Hydrogel Dressing with High Mechanical Strength and Water Resistance Used for Drug Delivery.

Hydrogel dressings provide a moist wound healing environment, absorb the exudates of the wound, and have better biocompatibility than traditional dressings. However, it is still difficult to meet the needs of modern medicine due to the defects in drug burst release, weak mechanical strength, and poor water retention. To solve these problems, we developed a double-layer (DL) hydrogel based on ß-cyclodextrin polymer (ß-CDP), poly(vinyl alcohol) (PVA), and carboxymethyl cellulose sodium (CMC) via a layer-by-layer method. Inspired by natural coconut, this hydrogel consisted of a drug release layer (DRL) and a mechanical support layer (MSL). In our design, the introduction of ß-CDP into the DRL slowed the drug release rate of the DL hydrogel. Furthermore, the mechanical strength of the hydrogel was improved by immersing the MSL in a calcium chloride/boric acid solution. Combining these two layers, the tensile strength and elongation at break of the DL hydrogel reached 1504 kPa and 400%, respectively. More interestingly, the release mechanism of DL hydrogel conformed to the diffusion-relaxation-erosion model, which was different from traditional hydrogel dressings. Therefore, the as-prepared DL structure represents a feasible solution for fabricating high-performance mechanical hydrogel dressings with sustained drug release properties, and the DL hydrogel has potential to be used for medical dressings applied in daily life.

Modular networks and genomic variation during progression from stable angina pectoris through ischemic cardiomyopathy to chronic heart failure.

BACKGROUND: Analyzing disease-disease relationships plays an important role for understanding etiology, disease classification, and drug repositioning. However, as cardiovascular diseases with causative links, the molecular relationship among stable angina pectoris (SAP), ischemic cardiomyopathy (ICM) and chronic heart failure (CHF) is not clear. METHODS: In this study, by integrating the multi-database data, we constructed paired disease progression modules (PDPMs) to identified relationship among SAP, ICM and CHF based on module reconstruction pairs (MRPs) of K-value calculation (a Euclidean distance optimization by integrating module topology parameters and their weights) methods. Finally, enrichment analysis, literature validation and structural variation (SV) were performed to verify the relationship between the three diseases in PDPMs. RESULTS: Total 16 PDPMs were found with K > 0.3777 among SAP, ICM and CHF, in which 6 pairs in SAP-ICM, 5 pairs for both ICM-CHF and SAP-CHF. SAP-ICM was the most closely related by having the smallest average K-value (K = 0.3899) while the maximum is SAP-CHF (K = 0.4006). According to the function of the validation gene, inflammatory response were through each stage of SAP-ICM-CHF, while SAP-ICM was uniquely involved in fibrosis, and genes were related in affecting the upstream of PI3K-Akt signaling pathway. 4 of the 11 genes (FLT1, KDR, ANGPT2 and PGF) in SAP-ICM-CHF related to angiogenesis in HIF-1 signaling pathway. Furthermore, we identified 62.96% SVs were protein deletion in SAP-ICM-CHF, and 53.85% SVs were defined as protein replication in SAP-ICM, while ICM-CHF genes were mainly affected by protein deletion. CONCLUSION: The PDPMs analysis approach combined with genomic structural variation provides a new avenue for determining target associations contributing to disease progression and reveals that inflammation and angiogenesis may be important links among SAP, ICM and CHF progression.

1,3-Dichloro-2-propanol induced ferroptosis through Nrf2/ARE signaling pathway in hepatocytes.

1,3-Dichloro-2-propanol (1,3-DCP) is a representative chloropropane environmental contaminant with multiple toxicities. Ferroptosis is a novel iron-dependent form of regulated cell death that is closely associated with the accumulation of lipid peroxides, Fe2+ and reactive oxygen species (ROS). In this study, we found that 1,3-DCP could induce mouse liver injury via ferroptosis. Administrating of C57BL/6J mice with 12.5, 25, and 50 mg/kg 1,3-DCP for 4 weeks via oral gavage, the data showed that 1,3-DCP exposure led to the pathological changes in mouse livers, remarkably induced accumulation of malondialdehyde (MDA) and Iron, reduction of glutathione (GSH), and changed in the expression of ferroptosis marker proteins glutathione peroxidase 4 (GPX4) and acyl-CoA synthetase-4 (ACSL4). Then, we also proved the results with HepG2 cells in vitro. The data showed that treatment 1,3-DCP significantly triggered the ferroptosis in vitro. Furthermore, we found that the ferroptosis-related signal pathways were significantly activated in mice livers and HepG2 cells in response to 1,3-DCP exposure. The data showed that 1,3-DCP induced ferroptosis by inhibiting nuclear factor erythroid 2-related factor 2 (Nrf2) translocation into nuclear and thereby suppressing the expression of its downstream target proteins including GPX4, ferritin heavy chain (FTH), ferroportin (FPN), cystine/glutamate transporter xCT (SLC7A11), and heme oxygenase 1 (HO-1). Taken together, our findings confirmed that 1,3-DCP induced ferroptosis via the Nrf2/ARE signaling pathway in hepatocytes. Our works provide new toxicity mechanisms of 1,3-DCP with ferroptosis on hepatocytes injury.

SIRT1/mTOR pathway-mediated autophagy dysregulation promotes Pb-induced hepatic lipid accumulation in HepG2 cells.

Lead (Pb) is a common and toxic metal pollutant in the ecological environment and has drawn significant attention due to its presence in various channels, including the use of lead-based paint, mineral extraction and smelting, exhaust gas from gasoline combustion. Autophagy is an essential catabolic pathway and blocked autophagy may result in abnormal lipid metabolism in liver. A body of evidence demonstrates that Pb exposure causes abnormal lipid droplet (LDs) accumulation in the liver, but the mechanism remains unknown. Here, we investigated whether Pb induced lipid accumulation by regulating autophagy in HepG2 cells. In this study, we found that Pb (50 µM) blocked the autophagy flux mainly by transcription factor EB (TFEB)-mediated impairment of lysosome formation and activity. Then we demonstrated that the dense lipid accumulation was observed upon Pb exposure, and induction of autophagy by the autophagy activator rapamycin (Rap) alleviated Pb-induced lipid accumulation, while suppression of autophagy by chloroquine (CQ) exacerbated Pb-induced lipid accumulation, suggested that Pb-induced autophagy blockage might be responsible for lipid accumulation. Moreover, we demonstrated that the SIRT1/mTOR pathway participated in Pb-induced autophagy dysregulation, leading to Pb-induced hepatic lipid accumulation. In summary, these results revealed a new insight into the relationship between Pb-caused autophagy dysregulation and lipid accumulation for the first time and highlight autophagy as a novel therapeutic target against Pb-induced hepatic lipid accumulation which supplying the theoretical basis and potential strategies for the intervention and treatment of Pb-related disease.

Aflatoxin B1 inhibited autophagy flux by inducing lysosomal alkalinization in HepG2 cells.

Aflatoxin B1 (AFB1) is a hazard food pollutant and the most toxic one of all the aflatoxins. It is mainly metabolized in the liver and exerts strong hepatotoxicity and carcinogenesis. Autophagy is an important biological process to maintain the homeostasis of intracellular environment. But the role of autophagy in AFB1-exposured hepatotoxicity remains unclear. The objective of this study was to explore the effect of AFB1 on autophagy flux and its potential mechanisms in HepG2 cells. The data showed AFB1 with no-observed adverse effect level (NOAEL) induced the accumulation of autophagosomes by detecting the level of LC3 and MDC staining. Subsequent findings revealed that autophagosome accumulation was caused by the inhibition of autophagy flux by transfection mRFP-GFP-LC3 adenovirus in the presence of autophagy inhibitor 3-MA and CQ. Further, we investigated lysosomal pH by Acridine orange (AO) and Lysotracker Red (LTR) staining and found that AFB1 exposure caused lysosomal alkalinization. These results indicated AFB1 with NOAEL could inhibit autophagy flux by inducing lysosomal alkalinization. Our study was helpful to further explain early hepatotoxicity mechanism of AFB1.

Pluripotent anti-inflammatory immunomodulatory effects of papaverine against cerebral ischemic-reperfusion injury.

The mechanism of the papaverine (PV) for the treatment of cerebral ischemia remains unclear. A total of 42 mice induced with focal cerebral ischemia were randomly divided into three groups: PV,baicalin (BA)and vehicle group. Both PV and BA could significantly reduce the ischemic infarct volume (P < 0.05). Pathway enrichment analysis was performed on MetaCore™ to search the molecular pathways associated with the gene expression profile of PV, compared with vehicle and BA. Compared with vehicle, we found that 60% of the top 10 pathways in PV group were related to immune response. The top 10 biological processes of the targeted pathways were mainly related to the multiple immunomodulatory process of neuro-vascular inflammation, including immune_Th17-deried cytokins, regulation of angiogenesis, cell adhesion_Leucocyte chemotaxis, antigen presentation, cell adhesion_synaptic contact, and inflammation related to Amphoterin signaling. Moreover, compared with BA, 17 pathways of PV were identified, and 58.82% (10/17) were also related to immune response, especially, half of the top 10 pathways with the lower p-value. In these top 10 pathways, 4 were the cytokine-mediated signaling pathways, which play key role in inflammation, like IL-17 signaling pathways with the activation of G-CSF,IL-23,RANKL, p38MAPK and NF-κB.These findings indicate that PV may be an efficacious pluripotent anti-inflammatory agent against cerebral ischemic-reperfusion injury by targeting on multiple immunomodulatory process of neuro-vascular inflammation.

Combined toxic effects of CBNPs and Pb on rat alveolar macrophage apoptosis and autophagy flux.

Carbon black (CB) and heavy metals are the main components of Particulate Matter (PM). Although the individual toxicities of CB and heavy metals have been extensively studied, the combined toxicity is much less understood. In this study, we choose the nano carbon black (CBNPs) and Pb2+ to simulate fine particles in the atmosphere and study the combined toxic effect on rat alveolar macrophages. The data showed that CBNPs could adsorb Pb2+ to form CBNPs-Pb2+ complex and displayed an altered physical properties by particle characterization. CBNPs-Pb2+ synergistically induced rat alveolar macrophages apoptosis and blocked autophagy flux compared with CBNPs and Pb2+ individually. Consistent with this, CBNPs-Pb2+ could impair the mitochondrial membrane potential (MMP), activate apoptotic signaling pathways, inhibit lysosomal function.

High strength hydrogels with multiple shape-memory ability based on hydrophobic and electrostatic interactions.

Hydrogels with multiple shape-memory ability have aroused great interest due to their promising applications in various fields. Nevertheless, the weak mechanical performance of most shape-memory hydrogels seriously impedes the practical application in more complex environments. Herein, we reported a novel hydrogel with both high mechanical and multi-shape memory properties composed of stearyl methacrylate (SMA), acrylic acid (AA) and quaternary chitosan (QCH). The electrostatic interactions between AA and QCH together with the hydrophobic interactions of alkyl chains in SMA endowed the hydrogel with great strain-stress and fatigue resistance. Furthermore, due to the reversible destruction and construction of physical cross-links, the prepared hydrogels also exhibited the shape-memory ability in response to different stimuli, such as temperature, pH and NaCl solution. Additionally, the multiple shape-memory effect could be accomplished via programmable combination because of the relatively independent physical interactions in the hydrogels.

A Neutrosophic Forecasting Model for Time Series Based on First-Order State and Information Entropy of High-Order Fluctuation.

In time series forecasting, information presentation directly affects prediction efficiency. Most existing time series forecasting models follow logical rules according to the relationships between neighboring states, without considering the inconsistency of fluctuations for a related period. In this paper, we propose a new perspective to study the problem of prediction, in which inconsistency is quantified and regarded as a key characteristic of prediction rules. First, a time series is converted to a fluctuation time series by comparing each of the current data with corresponding previous data. Then, the upward trend of each of fluctuation data is mapped to the truth-membership of a neutrosophic set, while a falsity-membership is used for the downward trend. Information entropy of high-order fluctuation time series is introduced to describe the inconsistency of historical fluctuations and is mapped to the indeterminacy-membership of the neutrosophic set. Finally, an existing similarity measurement method for the neutrosophic set is introduced to find similar states during the forecasting stage. Then, a weighted arithmetic averaging (WAA) aggregation operator is introduced to obtain the forecasting result according to the corresponding similarity. Compared to existing forecasting models, the neutrosophic forecasting model based on information entropy (NFM-IE) can represent both fluctuation trend and fluctuation consistency information. In order to test its performance, we used the proposed model to forecast some realistic time series, such as the Taiwan Stock Exchange Capitalization Weighted Stock Index (TAIEX), the Shanghai Stock Exchange Composite Index (SHSECI), and the Hang Seng Index (HSI). The experimental results show that the proposed model can stably predict for different datasets. Simultaneously, comparing the prediction error to other approaches proves that the model has outstanding prediction accuracy and universality.

[Core prescription excavation of launched Chinese patent medicines for treating different syndromes of angina pectoris].

To analyze the medication features and regularity of prescriptions of traditional Chinese medicines in treating patients with coronary heart disease angina pectoris based on the launched Chinese patent medicines. In the article,we collected all of the launched Chinese patent medicines for treating coronary heart disease and angina pectoris from the Chinese patent medicine value assessment information database,and set up a medical record normalized database,then carried out the classification of syndromes. The medication features and prescription rules for angina pectoris were analyzed by frequency statistics and association rules(IBM SPSS Modeler 14. 1 Premiums software,Apriori algorithm). Finally,a total of 170 prescriptions were selected,and 197 Chinese herbs were included,involving to totally 11 syndrome types,in which blood stasis syndrome,Qi stagnation and blood stasis syndrome,Qi deficiency and blood stasis syndrome,Qi-Yin deficiency and blood stasis syndrome were the main syndrome types. The frequency of single-herb medicines for the four main syndrome types,the combination of commonly used medicines,and the core prescriptions were summarized. After comparing the core prescriptions of the four syndrome types,we could analyze the medication features and prescription rules. In conclusion,the therapeutic principle is blood-activating and stasis-dissolving,and consideration was also given to promoting Qi,invigorating Qi and resuscitation and invigorating Qi-Yin. The main medicines include Danshen(Salvia Miltiorrhizae Radix et Rhizoma) and Chuan-xiong(Chuanxiong Rhizoma). According to different types of syndromes,Chinese herbal medicines are added,such as Jiangxiang(Dalbergiae Odoriferae Lignum), Chishao(Paeoniaeradix Rubra), Sanqi(Notoginseng Radix et Rhizoma), Honghua(Carthami Flos),Bingpian(Borneolum Syntheticum),Renshen(Ginseng Radix et Rhizoma). Frequency statistics and association rules are combined to explore the medication features and core prescriptions,which provide ideas for the treatment of angina pectoris and the development of new drugs.

A Forecasting Model Based on High-Order Fluctuation Trends and Information Entropy.

Most existing high-order prediction models abstract logical rules that are based on historical discrete states without considering historical inconsistency and fluctuation trends. In fact, these two characteristics are important for describing historical fluctuations. This paper proposes a model based on logical rules abstracted from historical dynamic fluctuation trends and the corresponding inconsistencies. In the logical rule training stage, the dynamic trend states of up and down are mapped to the two dimensions of truth-membership and false-membership of neutrosophic sets, respectively. Meanwhile, information entropy is employed to quantify the inconsistency of a period of history, which is mapped to the indeterminercy-membership of the neutrosophic sets. In the forecasting stage, the similarities among the neutrosophic sets are employed to locate the most similar left side of the logical relationship. Therefore, the two characteristics of the fluctuation trends and inconsistency assist with the future forecasting. The proposed model extends existing high-order fuzzy logical relationships (FLRs) to neutrosophic logical relationships (NLRs). When compared with traditional discrete high-order FLRs, the proposed NLRs have higher generality and handle the problem caused by the lack of rules. The proposed method is then implemented to forecast Taiwan Stock Exchange Capitalization Weighted Stock Index and Heng Seng Index. The experimental conclusions indicate that the model has stable prediction ability for different data sets. Simultaneously, comparing the prediction error with other approaches also proves that the model has outstanding prediction accuracy and universality.

Rapidly recoverable, anti-fatigue, super-tough double-network hydrogels reinforced by macromolecular microspheres.

In this study, a novel strategy was designed to prepare rapidly recoverable, anti-fatigue, super-tough double-network hydrogels by introducing macromolecular microspheres (MMs) as cross-linking centers for hydrophobic associations. MMs were prepared via emulsion polymerization using butyl acrylate (BA) as a main component and dicyclopentyl acrylate (DCPA) as a cross-linker. Then, a double-network (DN) hydrogel was prepared using gelatin as the first network and a copolymer of acrylamide and hexadecyl methacrylate stabilized by MMs as the second network. As a result, the DN hydrogels that were toughened by MMs exhibited an excellent fracture strength of 1.48 MPa and a fracture strain of 2100%. Moreover, the hydrogels exhibited rapid recoverability and fatigue resistance. Therefore, the strategy would open up a novel avenue for the toughening of DN hydrogels for biomedical applications.

Super-tough, ultra-stretchable and strongly compressive hydrogels with core-shell latex particles inducing efficient aggregation of hydrophobic chains.

Toughness, strechability and compressibility for hydrogels were ordinarily balanced for their use as mechanically responsive materials. For example, macromolecular microsphere composite hydrogels with chemical crosslinking exhibited excellent compression strength and strechability, but poor tensile stress. Here, a novel strategy for the preparation of a super-tough, ultra-stretchable and strongly compressive hydrogel was proposed by introducing core-shell latex particles (LPs) as crosslinking centers for inducing efficient aggregation of hydrophobic chains. The core-shell LPs always maintained a spherical shape due to the presence of a hard core even by an external force and the soft shell could interact with hydrophobic chains due to hydrophobic interactions. As a result, the hydrogels reinforced by core-shell LPs exhibited not only a high tensile strength of 1.8 MPa and dramatic elongation of over 20 times, but also an excellent compressive performance of 13.5 MPa at a strain of 90%. The Mullins effect was verified for the validity of core-shell LP-reinforced hydrogels by inducing aggregation of hydrophobic chains. The novel strategy strives to provide a better avenue for designing and developing a new generation of hydrophobic association tough hydrogels with excellent mechanical properties.

The toxic effects of benzo[a]pyrene on activated mouse T cells in vitro.

Benzo[a]pyrene (B[a]P) is a polycyclic aromatic hydrocarbon contaminant that is widely present in environmental sources, including food. This study aims to clarify the effects of B[a]P toxicity on activated mouse T cells in vitro. Our results show that B[a]P markedly inhibited Concanavalin A (ConA)-induced T lymphocyte proliferation and suppressed the production of the cytokines Interferon (IFN)-γ, Interleukin (IL)-2 and IL-4. Western blot and protein-DNA interaction assays were used to study how B[a]P affects signal transduction. The results revealed that B[a]P suppressed the ConA-induced activation of the Ca2+/CaM/NFκB and Ca2+/CaM/CaN/NFAT signal transduction pathways. These observations indicate that B[a]P has toxic effects on activated mouse T cells in vitro.

Immunosuppressive activity of alpinetin on activation and cytokines secretion of murine T lymphocytes.

Abstract Alpinetin, a flavonoid compound extracted from the seeds of Alpinia katsumadai Hayata, has been known to possess antibacterial, anti-inflammatory and other important therapeutic activities. In the current study, we investigated alpinetin for its immunosuppressive effect on activation and cytokines secretion of murine T lymphocytes. The data showed that alpinetin markedly suppressed ConA-induced murine splenocyte proliferation, Th1/Th2 cytokines production, CD4(+) T-cell populations and ratio of CD4(+)/CD8(+). This inspired us to further study the effects of alpinetin in vivo. The results showed that administration of alpinetin suppressed T-cell-mediated delayed-type hypersensitivity reaction in mice. In addition, we studied signal transduction pathways about T-cell activation on puried murine T lymphocytes by Western-blot assay. The data revealed that alpinetin could shock the activation of NF-κB, NFAT2 signal transduction pathways. These observations indicated that alpinetin have potential effects in downregulating the immune system and might be developed as a useful immunosuppressive agent in treating undesired immune responses.

Ginsenoside Rb1 alleviates 3-MCPD-induced renal cell pyroptosis by activating mitophagy.

Ginsenoside Rb1 (Gs-Rb1) is among the most significant effective pharmacological components in ginseng. 3-monochloropropane-1,2-diol (3-MCPD), a chloropropanol-like contaminant, is produced in the production of refined oils and thermal processing of food. Pyroptosis is a type of programmed cell death triggered by inflammasomes. Excessive pyroptosis causes kidney injury and inflammation. Previous studies have revealed that 3-MCPD induced pyroptosis in mice and NRK-52E cells. In the present study, we find that Gs-Rb1 attenuates 3-MCPD-induced renal cell pyroptosis by assaying GSDMD-N, caspase-1, IL-18, and IL-1ß in mice and NRK-52E cells. In further mechanistic studies, we show that Gs-Rb1 removes damaged mitochondria via mitophagy and reduces intracellular reactive oxygen species (ROS) generation, therefore alleviating 3-MCPD-induced NOD-like receptor family pyrin domain containing 3 (NLRP3) activation and pyroptosis. The above results are further validated by the addition of autophagy inhibitor Chloroquine (CQ) and mitophagy inhibitor Cyclosporin A (CsA). Afterward, we explore how Gs-Rb1 activated mitophagy in vitro. We determine that Gs-Rb1 enhances the protein expression and nuclear translocation of Transcription factor EB (TFEB). However, silencing of the TFEB gene by small interfering RNA technology reverses the role of Gs-Rb1 in activating mitophagy. Therefore, we conclude that 3-MCPD damages mitochondria and leads to ROS accumulation, which causes NLRP3 activation and pyroptosis in ICR mice and NRK-52E cells, while Gs-Rb1 mitigates this phenomenon via the TFEB-mitophagy pathway. Our findings may provide new insights for understanding the molecular mechanisms by which Gs-Rb1 mitigates renal injury.

3-Monochloropropane-1,2-diol esters induce HepG2 cells necroptosis via CTSB/TFAM/ROS pathway.

3-monochloropropane-1,2-diol esters (3-MCPDE) are toxic substances that form in food thermal processing and have a diverse range of toxicities. In this study, we found that 3-MCPDE triggered necroptosis by RIPK1/RIPK3/MLKL pathway in HepG2 cells. Previous studies have shown that ROS is an important activator of RIPK1 and RIPK3. The data showed that 3-MCPDE induced excessive ROS production through mitochondrial damage. After treatment with ROS inhibitor N-acetylcysteine (NAC), 3-MCPDE-induced necroptosis was relieved. Further, we explored how 3-MCPDE destroys mitochondria. The data suggested that 3-MCPDE induced mitochondrial dysfunction through the CTSB/TFAM pathway. Overall, the results indicated that 3-MCPDE induced necroptosis through CTSB/TFAM/ROS pathway in HepG2 cells. Our study provided a new mechanism for 3-MCPDE hepatotoxicity.

3-MCPD Induces Renal Cell Pyroptosis and Inflammation by Inhibiting ESCRT-III-Mediated Cell Repair and Mitophagy.

3-Monochloropropane-1,2-diol (3-MCPD) is a chloropropyl alcohol contaminant mainly from the thermal processing of food and could affect kidneys. Pyroptosis is programmed cell death mediated by inflammasomes and gasdermins, and excessive cellular pyroptosis and inflammation can lead to tissue injury. In the present study, we found that 3-MCPD increased lactate dehydrogenase (LDH) levels in vitro and in vivo, increased the protein expression of NOD-like receptor family pyrin domain containing 3 (NLRP3), N-terminal domain of GSDMD (GSDMD-N), and cleaved caspase-1 and promoted the release of interleukin-1ß (IL-1ß) and interleukin-18 (IL-18), which induced renal cell pyroptosis and inflammation. Mechanistic studies indicated that the addition of N-acetylcysteine (NAC), a ROS scavenger, inhibited NLRP3 activation and attenuated pyroptosis. Furthermore, we revealed that 3-MCPD induced ROS accumulation by inhibiting ESCRT-III-mediated mitophagy. These results were further validated by the overexpression of charged multivesicular body protein 4B (CHMP4B), a key subunit of ESCRT-III, and the addition of the mitophagy activator carbonyl cyanide m-chlorophenylhydrazone (CCCP) and rapamycin (Rapa). Thus, our results showed that 3-MCPD could induce mitochondrial damage and produce ROS. 3-MCPD suppressed mitophagy, leading to the accumulation of damaged mitochondria and ROS, thereby activating NLRP3 and pyroptosis. Meanwhile, 3-MCPD-mediated suppression of ESCRT-III hindered the repair of GSDMD-induced cell membrane rupture, which further caused the occurrence of pyroptosis. Our findings provide new perspectives for studying the mechanisms underlying 3-MCPD-induced renal injury.

Preparation, design, identification and application of self-assembly peptides from seafood: A review.

Hydrogels formed by self-assembling peptides with low toxicity and high biocompatibility have been widely used in food and biomedical fields. Seafood contains rich protein resources and is also one of the important sources of natural bioactive peptides. The self-assembled peptides in seafood have good functional activity and are very beneficial to human health. In this review, the sequence of seafood self-assembly peptide was introduced, and the preparation, screening, identification and characterization. The rule of self-assembled peptides was elucidated from amino acid sequence composition, amino acid properties (hydrophilic, hydrophobic and electric), secondary structure, interaction and peptide properties (hydrophilic and hydrophobic). It was introduced that the application of hydrogels formed by self-assembled peptides, which lays a theoretical foundation for the development of seafood self-assembled peptides in functional foods and the application of biological materials.