[Traditional Chinese medicine therapy for rheumatoid arthritis: a review].

Rheumatoid arthritis(RA) is an autoimmune disease that seriously affects the physical and mental health of patients, but its pathogenesis is still unclear. At present, clinical treatment drugs include conventional synthetic disease modifing anti-rheumatic drugs(csDMARDs), nonsteroid anti-inflammtory drugs(NSAIDs), hormones, small molecule targeted drugs, biological agents, etc. These drugs can relieve the clinical symptoms of most patients with RA to a certain extent, but there are still many limitations, such as drug adverse reactions and individual differences in drug efficacy. Therefore, the research on drug treatment targets and the development of low-toxicity drugs helps further improve the precise prevention, diagnosis, and treatment of RA. There is an urgent need for efficient and low-toxic treatments to delay the clinical progress of RA. As a treasure of Chinese culture, traditional Chinese medicine(TCM) is widely used as an alternative therapy in the treatment of various diseases, and has a significant clinical efficacy. TCM therapy(including monomer traditional Chinese medicine, classical compounds, and non-drug therapies) has a significant curative effect on RA. Based on the literature research in recent years, this paper reviewed the clinical and mechanism research of TCM therapy in the treatment of RA, and provided more in-depth thinking for the wide application of TCM therapy in clinical practice.

Enhanced antibacterial efficacy and mechanism of octyl gallate/beta-cyclodextrins against Pseudomonas fluorescens and Vibrio parahaemolyticus and incorporated electrospun nanofibers for Chinese giant salamander fillets preservation.

A series of alkyl gallates were evaluated for the antibacterial activity against two common Gram-negative foodborne bacteria (Pseudomonas fluorescens and Vibrio parahaemolyticus) associated with seafood. The length of the alkyl chain plays a pivotal role in eliciting their antibacterial activities and octyl gallate (OG) exerted an excellent inhibitory efficacy. To extend the aqueous solubility, stability, and bactericidal properties of octyl gallate (OG), an inclusion complex between OG and ß-cyclodextrin (ßCD), OG/ßCD, was prepared and identified with various methods including X-ray diffraction (XRD), differential scanning calorimeter (DSC) and Fourier transform infrared spectroscopy (FTIR). Furthermore, the enhanced inhibitory effect and potential antibacterial mechanism of OG/ßCD against two Gram-negative and Gram-positive foodborne bacteria were comprehensively investigated. The results show that OG/ßCD could function against bacteria through effectively damaging the membrane, permeating into cells, and then disturbing the activity of the respiratory electron transport chain to cause the production of high-level intracellular hydroxyl radicals. Moreover, the reinforced OG/ßCD-incorporated polylactic acid (PLA) nanofibers were fabricated using the electrospinning technique as food packaging to extend the Chinese giant salamander fillet's shelf life at 4 °C. This research highlights the antibacterial effectiveness of OG/ßCD in aqueous media, which can be used as a safe multi-functionalized food additive combined with the benefits of electrospun nanofibers to extend the Chinese giant salamander fillets shelf life by 15 d at 4 °C.

On the mechanism behind enhanced antibacterial activity of alkyl gallate esters against foodborne pathogens and its application in Chinese icefish preservation.

The objective of this study was to investigate antibacterial activities and action mode of alkyl gallates against three food-related bacteria. Results show that the length of the alkyl chain plays a critical role in eliciting their antibacterial activities and octyl gallate (GAC8) exhibited an outstanding bactericidal effect against these strains. A possible bactericidal mechanism of GAC8 against E. coli was fully elucidated by analyzing associated changes in cellular functions of E. coli, including assessments of membrane modification and intracellular oxidation state. Our data strongly suggested that GAC8 functions outside and inside the bacterial membrane and causes increased intracellular reactive oxygen species (hydroxyl radicals) and subsequent oxidative damage. We demonstrated that the hydroxyl radical formation induced by GAC8 is the end product of an oxidative damage cellular death pathway involving a transient depletion of NADH, the tricarboxylic acid cycle, intrinsic redox cycling activities, and stimulation of the Fenton reaction. Also, chitosan-based edible films containing GAC8 have unique superiorities for icefish preservation at 4 °C. This research highlights the effectiveness of GAC8 as an attractive antibacterial, which possesses both antioxidant and antibacterial activities and can be used as a multifunctional food additive combined with the benefit of active packaging for food preservations.

Antimicrobial effect and mechanism of non-antibiotic alkyl gallates against Pseudomonas fluorescens on the surface of Russian sturgeon (Acipenser gueldenstaedti).

Since Pseudomonas fluorescens is the main microorganism causing severe spoilage in refrigerated aquatic products, the searching for non-antibiotic antibacterial agents effective against it continues to receive increasing interest. This study aimed to investigate the antibacterial effects and mechanisms of alkyl gallic esters against P. fluorescens isolated from the Russian sturgeon (Acipenser gueldenstaedti), as well as the effectiveness in combination with chitosan films on the preservation of sturgeon meats at 4 °C. Our data shows that the alkyl chain length plays a significant role in eliciting their antibacterial activities and octyl gallate (GAC8) exhibited an outstanding inhibitory efficacy. GAC8 can rapidly enter into the membrane lipid bilayer portion to disorder the membrane, and further inhibit the growth of the P. fluorescens through interfering both tricarboxylic acid cycle related to energy supply and amino acid metabolism associated with cell membranes, suppressing oxygen consumption and disturbing the respiration chain. Moreover, the alteration in membrane fatty acids indicated that GAC8 could disrupt the composition of cell membrane fatty acids, rendering the bacteria more sensitive to the antibacterial. The SEM results also substantiate the damage of the structure of the bacterial membrane caused by GAC8. Additionally, the edible chitosan-based films incorporated with GAC8 showed the enhanced antibacterial efficacy to remarkably extend the shelf life of Russian sturgeon. Overall, our findings not only provide new insight into the mode of action of GAC8 against P. fluorescens but also demonstrate composite films containing GAC8, as a kind of safe and antibacterial material, have a great promise for application in food preservations.

Antimicrobial mechanism of alkyl gallates against Escherichia coli and Staphylococcus aureus and its combined effect with electrospun nanofibers on Chinese Taihu icefish preservation.

The objective of this study was to investigate the antibacterial activity and potential mechanism of alkyl gallates against Escherichia coli and Staphylococcus aureus. Results show that the length of the alkyl chain plays a pivotal role in eliciting the activity and octyl gallate (OG) exerted excellent bactericidal activity through a multiple bactericidal mechanism. OG functions against both bacteria through damaging bacterial cell wall integrity, permeating into cells and then interacting with DNA, as well as disturbing the activity of the respiratory electron transport chain to induce a high-level toxic ROS (hydroxyl radicals) generation and up-regulation of the ROS genes. Also, electrospun nanofibers with OG have unique superiorities for maintaining the freshness of the icefish (4 °C). This research not only provides a more in-depth understanding of the interaction between OG and microorganisms but also highlights the great promise of using OG as a safe multi-functionalized food additive for food preservations.

Lipophilic ferulic acid derivatives protect PC12 cells against oxidative damage via modulating ß-amyloid aggregation and activating Nrf2 enzymes.

Ferulic acid (FA) has been shown to have a neuroprotective effect on Alzheimer's disease induced by amyloid-beta (Aß) neurotoxicity. This work aims to ascertain the structure-activity relationship of FA and its alkyl esters (FAEs) for evaluating the antioxidant activities in PC12 cells and Aß1-42 aggregation inhibitory activities in vitro, as well as the signaling mechanisms against oxidative stress elicited by Aß1-42 in PC12 cells. Our data showed that alterations in the subcellular localization and cytotoxicity of FAEs caused by the lipophilicity of FA were crucial when evaluating their antioxidant capacities. Pre-treating cells with butyl ferulate (FAC4) significantly attenuated Aß1-42-evoked intracellular ROS formation. Besides, FAC4 exhibited the highest Aß1-42 aggregation inhibitory effectiveness. The molecular docking results showed that FAC4 binds to amide NH in Gln15 and Lys16 via a hydrogen bond. Notably, FAC4 could upregulate antioxidant defense systems by modulating the Keap1-Nrf2-ARE signaling pathway. Identification of the functions of FAEs could be useful in developing food supplements or drugs for treating AD.

Evaluation of antibacterial and anti-biofilm properties of kojic acid against five food-related bacteria and related subcellular mechanisms of bacterial inactivation.

Although the antimicrobial properties of kojic acid have been recognized, the subcellular mechanism of bacterial inactivation caused by it has never been clearly elucidated. In the present study, the antibacterial and anti-biofilm activity of kojic acid was evaluated against five foodborne pathogens including Listeria monocytogenes, Bacillus subtilis, Staphylococcus aureus, Escherichia coli, and Salmonella typhimurium. The antibacterial activity was determined by minimum inhibitory concentration, minimum bactericidal concentration, and the time-kill assay. Among them, the susceptibility of Escherichia coli was significant with the lowest minimum inhibitory concentration and minimum bactericidal concentration values of 10 and 20 mM, respectively. Subcellular mechanism of bacterial inactivation related to kojic acid was revealed through comprehensive factors including cell morphology, membrane permeability, K+ leakage, zeta potential, intracellular enzyme, and DNA assay. Results demonstrated that bacterial inactivation caused by kojic acid, especially for Gram-negative bacteria, was primarily induced by the pronounced damage to the cell membrane integrity. Leakage of intracellular enzyme to the supernatants implied that the cell membrane permeability was compromised. Consequently, the release of K+ from the cytosol leads to the alterations of the zeta potential of cells, which would disturb the subcellular localization of some proteins and thereby cause the bacterial inactivation. The free -CH2OH group at the C-2 of kojic acid could play more significant role in the antimicrobial performance of kojic acid against Gram-negative bacteria. Moreover, remarkable interaction with DNA was also observed. Kojic acid at sub-minimum inhibitory concentration inhibited biofilm formation by these bacteria.

Alkyl Ferulate Esters as Multifunctional Food Additives: Antibacterial Activity and Mode of Action against Escherichia coli in Vitro.

This work aims to prepare ferulic acid alkyl esters (FAEs) through the lipase-catalyzed reaction between methyl ferulate and various fatty alcohols in deep eutectic solvents and ascertain their antibacterial activities and mechanisms. Screens of antibacterial effects of FAEs against Escherichia coli ATCC 25922 ( E. coli) and Listeria monocytogenes ATCC 19115 ( L. monocytogenes) revealed that hexyl ferulate (FAC6) exerted excellent bacteriostatic and bactericidal effects on E. coli and L. monocytogenes (minimum inhibitory concentration (MIC): 1.6 and 0.1 mM, minimum bactericidal concentration (MBC): 25.6 and 0.2 mM, respectively). The antibacterial mechanism of FAC6 against E. coli was systematically studied to facilitate its practical use as a food additive with multifunctionalities. The growth and time-kill curves implied the partial cell lysis and inhibition of the growth of E. coli caused by FAC6. The result related to propidium iodide uptake and cell constituents' leakage (K+, proteins, nucleotides, and ß-galactosidase) implied that bacterial cytomembranes were substantially compromised by FAC6. Variations on morphology and cardiolipin microdomains and membrane hyperpolarization of cells visually verified that FAC6 induced cell elongation and destructed the cell membrane with cell wall perforation. SDS-PAGE analysis and alterations of fluorescence spectra of bacterial membrane proteins manifested that FAC6 caused significant changes in constitutions and conformation of membrane proteins. Furthermore, it also could bind to minor grooves of E. coli DNA to form complexes. Meanwhile, FAC6 exhibited antibiofilm formation activity. These findings indicated that that FAC6 has promising potential to be developed as a multifunctional food additive.

Data on the experiments of temperature-sensitive hydrogels for pH-sensitive drug release and the characterizations of materials.

This article contains experimental data on the strain sweep, the calibration curve of drug (doxorubicin, DOX) and the characterizations of materials. Data included are related to the research article "Injectable and body temperature sensitive hydrogels based on chitosan and hyaluronic acid for pH sensitive drug release" (Zhang et al., 2017) [1]. The strain sweep experiments were performed on a rotational rheometer. The calibration curves were obtained by analyzing the absorbance of DOX solutions on a UV-vis-NIR spectrometer. Molecular weight (Mw ) of the hyaluronic acid (HA) and chitosan (CS) were determined by gel permeation chromatography (GPC). The deacetylation degree of CS was measured by acid base titration.

Lipase-Catalyzed Synthesis of Sucrose Monolaurate and Its Antibacterial Property and Mode of Action against Four Pathogenic Bacteria.

The aim of this work was to evaluate the antibacterial activities and mode of action of sucrose monolaurate (SML) with a desirable purity, synthesized by Lipozyme TL IM-mediated transesterification in the novel ionic liquid, against four pathogenic bacteria including L. monocytogenes, B. subtilis, S. aureus, and E. coli. The antibacterial activity was determined by minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and the time⁻kill assay. SML showed varying antibacterial activity against tested bacteria with MICs and MBCs of 2.5 and 20 mM for L. monocytogenes, 2.5 and 20 mM for B. subtilis, 10 and 40 mM for S. aureus, respectively. No dramatic inhibition was observed for E. coli at 80 mM SML. Mechanism of bacterial inactivation caused by SML was revealed through comprehensive factors including cell morphology, cellular lysis, membrane permeability, K⁺ leakage, zeta potential, intracellular enzyme, and DNA assay. Results demonstrated that bacterial inactivation against Gram-positive bacteria was primarily induced by the pronounced damage to the cell membrane integrity. SML may interact with cytoplasmic membrane to disturb the regulation system of peptidoglycan hydrolase activities to degrade the peptidoglycan layer and form a hole in the layer. Then, the inside cytoplasmic membrane was blown out due to turgor pressure and the cytoplasmic materials inside leaked out. Leakage of intracellular enzyme to the supernatants implied that the cell membrane permeability was compromised. Consequently, the release of K⁺ from the cytosol lead to the alterations of the zeta potential of cells, which would disturb the subcellular localization of some proteins, and thereby causing bacterial inactivation. Moreover, remarkable interaction with DNA was also observed. SML at sub-MIC inhibited biofilm formation by these bacteria.

Injectable and body temperature sensitive hydrogels based on chitosan and hyaluronic acid for pH sensitive drug release.

Hydrogels based on chitosan/hyaluronic acid/ß-sodium glycerophosphate demonstrate injectability, body temperature sensitivity, pH sensitive drug release and adhesion to cancer cell. The drug (doxorubicin) loaded hydrogel precursor solutions are injectable and turn to hydrogels when the temperature is increased to body temperature. The acidic condition (pH 4.00) can trigger the release of drug and the cancer cell (Hela) can adhere to the surface of the hydrogels, which will be beneficial for tumor site-specific administration of drug. The mechanical strength, the gelation temperature, and the drug release behavior can be tuned by varying hyaluronic acid content. The mechanisms were characterized using dynamic mechanical analysis, Fourier transform infrared spectroscopy, scanning electron microscopy and fluorescence microscopy. The carboxyl group in hyaluronic acid can form the hydrogen bondings with the protonated amine in chitosan, which promotes the increase of mechanical strength of the hydrogels and depresses the initial burst release of drug from the hydrogel.

Differences in the viscoelastic features of white and grey matter in tension.

Owing to its higher stiffness, white matter can absorb more energy than grey matter at strain rates of 0.025, 0.15 and 0.25 /s in tension. The reverse trend was observed at low strain rate (0.005 /s) due to the enhanced interactions between biomolecules in white matter, which may originate from the presence of strong polar groups and the stronger hydrogen bonding, as evidenced by differential scanning calorimetry and Fourier transform infrared spectrometer spectra.

Micro/nano-particle decorated metal wire for cutting soft matter.

To cut soft materials such as biological tissues with minimal damage and reduced positional error is highly desired in medical surgery and biomechanics. After years of natural selection and evolution, mosquitoes have acquired the ability to insert their proboscises into human skin with astonishingly tiny forces. This can be associated with the unique structure of their proboscises, with micro/nano sawteeth, and the distinctive insertion manner: high frequency reciprocating saw cutting. Inspired by these, this communication describes the successful implantation of metal oxide particles onto molybdenum wire surfaces through a sol-calcination process, to form a biomimetic sawblade with a high density of micro/nano saw teeth, where the acidification is essential in terms of generating active anchoring sites on the wire. When used as a sawblade in conjunction with reciprocating action to cut the viscoelastic gel, both the cut-in force and cut-in displacement could be decreased substantially. The cutting speed and frequency of reciprocating action are important operating parameters influencing cut-in force.