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The hydrogels with injectable and self-healing properties were prepared from xanthan gum (XG) and silk fibroin (SF) by using sodium trimetaphosphate (STMP) as crosslinker. A three-stage model of oscillation-shear-oscillation experiment was designed to mimic injection process and to observe destruction and regeneration of the hydrogels after shear. The XG3-SF-STMP hydrogels immediately recovered to original storage modulus of 80.6%–93.8% on removing shear. The hydrogels were 3D printed into the self-supporting constructions of hydrogel fibers with connected porous structures, and the XG3-SF-STMP hydrogel fibers exhibited smaller width than XG3-STMP. Oscillation rheological behavior indicated that XG3-SF-STMP hydrogels formed rapidly and exhibited more solid-like gel behavior than XG3-STMP. The hydrogel structures were destroyed under a strain (100%) larger than critical strain, but were rebuilt under a small strain (1%) with recovery ratio of 91.36–93.96% within 120 s, suggesting a self-healing property. Introduction of SF particles into XG3-STMP crosslinked networks improved stiffness and retained recoverability. Carboxyl and phosphate groups in the hydrogel networks are beneficial for XG3-SF-STMP hydrogels to absorb enough liquid electrolytes, leading to effective ionic conductivity. The ion-conductive hydrogel with injectable, self-healing, controlled release and non-cytotoxic properties possesses a promising prospect for tissue engineering and drug release application.

Cardiovascular diseases (CVD), including ischemic heart diseases and cerebrovascular diseases, are the leading causes of morbidity and mortality worldwide. Atherosclerosis is the major underlying factor for most CVD. It is well-established that oxidative stress and inflammation are two major mechanisms leading to atherosclerosis. Under oxidative stress, polyunsaturated fatty acids (PUFA)-containing phospholipids and cholesterol esters in cellular membrane and lipoproteins can be readily oxidized through a free radical-induced lipid peroxidation (LPO) process to form a complex mixture of oxidation products. Overwhelming evidence demonstrates that these oxidized lipids are actively involved in the inflammatory responses in atherosclerosis by interacting with immune cells (such as macrophages) and endothelial cells. In addition to lipid lowering in the prevention and treatment of atherosclerotic CVD, targeting chronic inflammation has been entering the medical realm. Clinical trials are under way to lower the lipoprotein (a) (Lp(a)) and its associated oxidized phospholipids, which will provide clinical evidence that targeting inflammation caused by oxidized lipids is a viable approach for CVD. In this review, we aim to give an update on our understanding of the free radical oxidation of LPO, analytical technique to analyze the oxidation products, especially the oxidized phospholipids and cholesterol esters in low density lipoproteins (LDL), and focusing on the experimental and clinical evidence on the role of lipid oxidation in the inflammatory responses associated with CVD, including myocardial infarction and calcific aortic valve stenosis. The challenges and future directions in understanding the role of LPO in CVD will also be discussed.

Titanium dioxide nanoparticles (TiO2 NPs) are widely used in food and cosmetics but the health impact of human exposure remains poorly defined. Emerging evidence suggests that TiO2 NPs may elicit immune responses by acting on macrophages. Our proteomic study showed that treatment of macrophages with TiO2 NPs led to significant re-organization of cell membrane and activation of inflammation. These observations were further corroborated with transmission electron microscopy (TEM) experiments, which demonstrated that TiO2 NPs were trapped inside of multi-vesicular bodies (MVB) through endocytotic pathways. TiO2 NP caused significant mitochondrial dysfunction by increasing levels of mitochondrial reactive oxygen species (ROS), decreasing ATP generation, and decreasing metabolic flux in tricarboxylic acid (TCA) cycle from 13C-labelled glutamine using GC-MS-based metabolic flux analysis. Further lipidomic analysis showed that TiO2 NPs significantly decreased levels of cardiolipins, an important class of mitochondrial phospholipids for maintaining proper function of electron transport chains. Furthermore, TiO2 NP exposure activates inflammatory responses by increasing mRNA levels of TNF-α, iNOS, and COX-2. Consistently, our targeted metabolomic analysis showed significantly increased production of COX-2 metabolites including PGD2, PGE2, and 15d-PGJ2. In addition, TiO2 NP also caused significant attenuation of phagocytotic function of macrophages. In summary, our studies utilizing multiple powerful omic techniques suggest that human exposure of TiO2 NPs may have profound impact on macrophage function through activating inflammatory responses and causing mitochondrial dysfunction without physical presence in mitochondria.

Hydrogels with thixotropic and pH-sensitive properties exhibit injectablity and response to external stimulation. Thixotropic and pH-responsive hydrogels were fabricated from xanthan gum (XG) and a hyperbranched β-D-glucan (TM3a) crosslinked with sodium trimetaphosphate (STMP) for injectable and release-controlled application. Thixotropy and creep-recovery tests were carried out to determine injectable and viscoelastic properties of the XG-TM3a-STMP hydrogels. Introduction of TM3a and formation of chemically crosslinking structures resulted in higher yield stress (43.6–168.9 Pa) and elastic modulus (146.9–1245.7 Pa), lower retardation time (32.6–44.4 s), and higher recovery percentage (49.5–66.7%) for XG-TM3a-STMP compared to XG-STMP and XG-TM3a-water. FTIR spectra and SEM observation demonstrated that TM3a disassembled XG aggregates by partially breaking hydrogen bonds, resulting in a relatively thin wall of the grids for XG-TM3a-STMP. The XG-TM3a-STMP hydrogels exhibited pH dependant swelling property and controlled release behavior. The hybrid hydrogels have potential applications in 3D printing or injectable tissue engineering and drug release fields.

Mitochondrial lipids are essential for maintaining the integrity of mitochondrial membranes and the proper functions of mitochondria. As the "powerhouse" of a cell, mitochondria are also the major cellular source of reactive oxygen species (ROS). Oxidative stress occurs when the antioxidant system is overwhelmed by overproduction of ROS. Polyunsaturated fatty acids in mitochondrial membranes are primary targets for ROS attack, which may lead to lipid peroxidation (LPO) and generation of reactive lipids, such as 4-hydroxynonenal. When mitochondrial lipids are oxidized, the integrity and function of mitochondria may be compromised and this may eventually lead to mitochondrial dysfunction, which has been associated with many human diseases including cancer, cardiovascular diseases, diabetes, and neurodegenerative diseases. How mitochondrial lipids are oxidized and the underlying molecular mechanisms and pathophysiological consequences associated with mitochondrial LPO remain poorly defined. Oxidation of the mitochondria-specific phospholipid cardiolipin and generation of bioactive lipids through mitochondrial LPO has been increasingly recognized as an important event orchestrating apoptosis, metabolic reprogramming of energy production, mitophagy, and immune responses. In this review, we focus on the current understanding of how mitochondrial LPO and generation of bioactive lipid mediators in mitochondria are involved in the modulation of mitochondrial functions in the context of relevant human diseases associated with oxidative stress.

To improve water stability of hydrophilic nanofibers, photocrosslinked maleilated chitosan/methacrylated poly (vinyl alcohol) (MCS/MPVA) bicomponent nanofibrous scaffolds were successfully obtained by electrospinning of aqueous MCS/MPVA solution and consequent photopolymerization. The parameters of MCS/MPVA solutions such as viscosity and conductivity were measured to evaluate electrospinnability of the blend solutions. The bicomponent nanofibrous scaffolds were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD) analysis and differential scanning calorimetry (DSC), respectively. SEM results indicated that MCS/MPVA weight ratios significantly influenced the morphology and diameter distribution of the nanofibers. XRD and DSC investigated that there was strong interaction caused by hydrogen bonding between molecular chain of MCS and MPVA. Water stability test confirmed that the photocrosslinked matrix with a MCS/MPVA ratio of 10/90 retained excellent integrity of the fibrous structure in water. The in vitro cytotoxicity evaluation revealed that photocrosslinked nanofibrous scaffolds entailed good cellular compatibility, and could be used as potential wound dressing.

Altered redox status in cancer cells has been linked to lipid peroxidation induced by reactive oxygen species (ROS) and subsequent formation of reactive lipid electrophiles, especially 4-hydroxy-nonenal (4-HNE). Emerging evidence suggests that cancer cells manipulate redox status to acquire anti-apoptotic phenotype but the underlying mechanisms are poorly understood. Cardiolipin (CL), a mitochondria-specific inner membrane phospholipid, is critical for maintaining mitochondrial function. Paradoxically, liver tissues contain tetralinoleoyl cardiolipin (TLCL) as the major CL in mitochondria yet emerging evidence suggests that ROS generated in mitochondria may lead to CL peroxidation and activation of intrinsic apoptosis. It remains unclear how CL oxidation leads to apoptosis and its relevance to the pathogenesis of hepatocellular carcinoma (HCC). We employed a mass spectrometry-based lipidomic approach to profile lipids in human tissues of HCC and found that CL was gradually decreased in tumor comparing to peripheral non-cancerous tissues, accompanied by a concomitant decrease of oxidized CL and its oxidation product, 4-HNE. Incubation of liver cancer cells with TLCL significantly restored apoptotic sensitivity accompanied by an increase of CL and its oxidation products when treated with staurosporine (STS) or Sorafenib (the standard treatment for late stage HCC patients). Our studies uncovered a novel mechanism by which cancer cells adopt to evade apoptosis, highlighting the importance of mitochondrial control of apoptosis through modulation of CL oxidation and subsequent 4-HNE formation in HCC. Thus manipulation of mitochondrial CL oxidation and lipid electrophile formation may have potential therapeutic value for diseases linked to oxidative stress and mitochondrial dysfunctions.

Xanthan-based hydrogels can be used for encapsulating and controlling release of nutrition ingredients, therapeutic agents, and cells in food and tissue engineering applications. Hydroxyl groups on the xanthan gum (XG) chains permitted the formation of the hydrogels through crosslinking XG with sodium trimetaphosphate (STMP). Dynamical oscillation tests were performed to monitor the in situ crosslinking process, and to evaluate the forming kinetics and mechanical stability for the XG-STMP hydrogels. The results indicated that the transition from hydrogen bonding to chemical crosslinking for the XG chains occurred and reached a balance approximately at 25 and 37 °C, respectively. The XG-STMP hydrogel networks with solid-like gel behavior exhibited more elastic and tougher to resist the deformation than the physical XG hydrogels. The XG-STMP hydrogels with porous and interconnected structure displayed good swelling and release-controlled properties. This work provides some valuable and fundamental information of the xanthan-based hydrogels for further application in biomaterials, medical and food engineering.

The well-documented anticarcinogenic properties of natural polyphenolic proanthocyanidins (OPC) have been primarily attributed to their antioxidant and anti-inflammatory potency. Emerging evidence suggests that OPC may target canonical oncogenic pathways, including PI3K/AKT; however, the underlying mechanism and therapeutic potential remain elusive. Here we identify that proanthocyanidin B2 (OPC–B2) directly binds and inhibits AKT activity and downstream signalling, thereby suppressing tumour cell proliferation and metabolism in vitro and in a xenograft and diethyl-nitrosamine (DEN)-induced hepatocellular carcinoma (HCC) mouse models. We further find that OPC-B2 binds to the catalytic and regulatory PH domains to lock the protein in a closed conformation, similar to the well-studied AKT allosteric inhibitor MK-2206. Molecular docking and dynamic simulation suggest that Lys297 and Arg86 are critical sites of OPC-B2 binding; mutation of Lys297 or Arg86 to alanine completely abolishes the antitumor effects of OPC-B2 but not MK-2206. Together, our study reveals that OPC-B2 is a novel allosteric AKT inhibitor with potent anti-tumour efficacy beyond its antioxidant and anti-inflammatory properties., Graphical abstract Image 1, Highlights • OPC-B2 exerts potent anti-tumor effects in HCC. • OPC-B2 directly binds to AKT and inhibits its kinase activity. • Lys297 and Arg86 in AKT are critical sites for OPC-B2/AKT interaction. • Allosteric inhibition of AKT by OPC-2 has therapeutic potential for HCC.

Bacterially derived lipopolysaccharide (LPS) stimulates naive B lymphocytes to differentiate into immunoglobulin (Ig)-secreting plasma cells. Differentiation of B lymphocytes is characterized by a proliferative phase followed by expansion of the intracellular membrane secretory network to support Ig production. A key question in lymphocyte biology is how naive B cells reprogram metabolism to support de novo lipogenesis necessary for proliferation and expansion of the endomembrane network in response to LPS. We report that extracellularly acquired glucose is metabolized, in part, to support de novo lipogenesis in response to LPS stimulation of splenic B lymphocytes. LPS stimulation leads to increased levels of endogenous ATP-citrate lyase (ACLY), and this is accompanied by increased ACLY enzymatic activity. ACLY produces cytosolic acetyl-CoA from mitochondrially derived citrate. Inhibition of ACLY activity in LPS-stimulated B cells with the selective inhibitor 2-hydroxy-N-arylbenzenesulfonamide (compound-9; C-9) blocks glucose incorporation into de novo lipid biosynthesis, including cholesterol, free fatty acids, and neutral and acidic phospholipids. Moreover, inhibition of ACLY activity in splenic B cells results in inhibition of proliferation and defective endomembrane expansion and reduced expression of CD138 and Blimp-1, markers for plasma-like B cell differentiation. ACLY activity is also required for LPS-induced IgM production in CH12 B lymphoma cells. These data demonstrate that ACLY mediates glucose-dependent de novo lipogenesis in response to LPS signaling and identify a role for ACLY in several phenotypic changes that define plasma cell differentiation.

The dilute solution properties, critical coil overlap concentration, and rheological properties of the hyperbranched PTM3b polysaccharide were studied and compared. Flory factor (Φ) values of PTM3b in different solvents were smaller than those of linear chains as a result of the hyperbranched structure and wide polydispersity index. The relationships of ‘zero shear’ specific viscosity (ηsp,0) and coil overlap parameter (c[η]) were represented as η s p , 0 ∝ c 1.05 ± 0.03 , η s p , 0 ∝ c 1.45 ± 0.03 and η s p , 0 ∝ c 2.89 ± 0.11 for the dilute, semi-dilute, and concentrated solution regions of PTM3b in 0.15 M aqueous NaCl, and coil overlap parameters were c*[η] = 0.07 and c**[η] = 0.29. Shear-thinning behavior was observed for PTM3b in 0.15 M aqueous NaCl in high concentration region, whereas Newtonian behavior in relatively low concentration region. The slope values of 2.34 and 12.8 were obtained from the double logarithmic plot of η0 versus c for PTM3b in 0.15 M aqueous NaCl. The slope value of 12.8 suggested that the hyperbranched polysaccharide resembled incompressible coils in the higher concentrated region. This work could provide some valuable and fundamental information to further understand the natural hyperbranched polysaccharide solutions from dilute to concentrated regions.

Chitin/alginate magnetic nano-gel beads (MCAs) were successfully prepared from 8 wt.% NaOH/4 wt.% urea aqueous solution by ionic cross-linking. Their structure and properties were investigated using scanning electron microscopy, X-ray diffraction, and vibrating sample magnetometry. The results showed that the magnetic iron oxide nanoparticles synthesized in situ with a mean diameter of 30 nm were uniformly dispersed and immobilized in the chitin/alginate matrix. The structure and nature of iron oxide were conserved perfectly, and the MCAs had extremely small hysteresis loop and low coercivity. Moreover, MCAs could efficiently adsorb the methyl orange from wastewater. The iron oxide nanoparticles in the MCAs played an important role in both the creation of the magnetic-induced transference and the improvement of the adsorption capacity. This work provides a novel, low-cost, simple, and “green” process for synthesizing the chitin-based magnetic nanocomposite gel beads, which had potential application on the removal of hazardous materials.

Four kinds of natural chitin originating from crab (C1), shrimp (C2), silkworm chrysalis (C3) and flies shell (C4) were dissolved in 8 wt.% NaOH/4 wt.% urea aqueous solution. Dilute solution behavior of chitin was examined by laser light scattering and viscometry. The Mark–Houwink equation and the relationship between the z -average radius of gyration ( R g ) and the average-weight molecular ( M w ) for C1 in the solvent at 25 °C were determined to be [ η ] = 0.26 M w 0.56±0.02 (mL g −1 ) and R g = 0.15 M w 0.47±0.03 (nm), respectively. On the basis of the polymer solution theory, the conformation parameters of C1 to C4 samples were calculated to be in the range of 25–18 nm for the length of the Kuhn statistical segment ( Q k ), and 43–32 for the characteristic ratio ( C ∞ ), respectively. It indicated that chitin molecules existed in a random-coil chain conformation, and chain flexibility increases from C1 to C4 in NaOH/urea aqueous system.

Two water-soluble polysaccharide-protein complexes, extracted from Pleurotus tuber-regium sclerotia, were modified chemically to obtain their sulfated and carboxymethylated derivatives. While C6 position of glucan was fully substituted, C2, C3, and C4 were only partially substituted by sulfate groups. C3, C4, and C6 position of glucan were partially substituted during the carboxymethylation. Chain conformation and antitumor activity of the native samples and their derivatives were studied. The native samples and derivatives existed in sphere conformation, and showed potent in vitro antitumor activities. Water-solubility and introduction of ionic groups played important roles in enhancing the antitumor activities of the polysaccharide-protein complexes.

A water soluble glucan, PLB-2C, was isolated from the water extract of the root of Pueraria lobata (Willd) Ohwi using anion-exchange and gel permeation chromatography. Its structure was investigated by gas chromatography (GC), gas chromatography–mass spectrometry (GC–MS), infrared (IR) spectra, and nuclear magnetic resonance (NMR) spectroscopy of heteronuclear single quantum coherence (HSQC) and heteronuclear multiple bond correlation (HMBC) techniques. The results indicated that PLB-2C was a linear glucan composed of (1 → 6)-α- d -Glcp. Chain conformation study showed that the polysaccharide took random coil compact conformation. In vitro cell viability assay by MTT method, its sulfated derivative PLB-2CS which was substituted at 2-O, 3-O, 4-O positions, at 0.1, 1, and 5 mg/ml, could attenuate PC12 cell damage significantly caused by hydrogen peroxide.

The optimal conditions for ZX-5, a newly isolated PNS bacterial strain, to produce hydrogen and the potential for it to treat wastewater were investigated. The strain could grow and produce hydrogen at pH 5.5–9.5, and it was able to adjust the pH value to about 7 during photo-fermentation by itself. ZX-5 could use 22 tested carbon sources for growth, and 15 of these carbon sources to produce hydrogen. The hydrogen conversion efficiencies of ZX-5 from succinate, lactate, butyrate, malate, acetate, pyruvic acid, propionate, d -mannitol and glucose were 89.7, 81.5, 71.5, 78.8, 69.0, 72.6, 61.9, 64.5, and 52.6%, respectively. The highest hydrogen-producing rate of 118 ml/l h was observed when butyrate was used as a carbon source. Relatively high efficiencies for reducing chemical oxygen demand ( > 80 % ) and hydrogen production were achieved when ZX-5 was used for photo-fermentation of succinate wastewater, or effluents from dark fermentation of wastewater from a fuel ethanol manufacturer or kitchen waste. The concentration of total fatty acids was 0.001 % after photo-fermentation by ZX-5. The above results suggest that ZX-5 would possess the potential for hydrogen production while treating wastewater.

We demonstrate a two-step process used to increase the hydrogen yield from sucrose and to relieve the pollution threat caused by resultant fatty acids in dark-fermentation. In batch tests of dark-fermentation using microflora, the maximum hydrogen production rate was > 360 mL H 2 / L h and the maximum hydrogen yield was 3.67 mol H 2 / mol sucrose. The fatty acids produced in dark-fermentation were mainly butyrate and acetate with a small amount of propionate, valerate, n-butyl alcohol, and caproate. Photo-fermentation with Rhodobacter sphaeroides SH2C was then employed to convert these small molecular fatty acids into hydrogen. The total hydrogen yield from sucrose increased from the maximum of 3.67 mol H 2 / mol sucrose in dark-fermentation to 6.63 mol H 2 / mol sucrose by using the two-step process. No butyrate, acetate, propionate, or valerate was detected in the final fermentation effluent after photo-fermentation. Our results suggest that a two-step process of combining dark- and photo-fermentation may increase hydrogen production capacity from biomass and prevent the environmental problems associated with untreated fermentation effluents.

A water-soluble hyperbranched beta-glucan, coded as TM3b, extracted from sclerotia of an edible fungus (Pleurotus tuber-regium) was fractioned into eight fractions coded as F1-F8 by a nonsolvent addition method. Five fractions were treated with chlorosulfonic acid at 35 degrees C to synthesize successfully sulfated derivatives coded as S-F2, S-F3, S-F4, S-F5, and S-F8 with degree of substitution of 0.28-0.54. The 13C NMR results of these sulfated beta-glucans indicated that while the C-6 position was fully substituted, C-2, C-3, and C-4 were only partially substituted by the sulfate groups. The weight-average molecular weights (Mw) and intrinsic viscosities ([eta]) of the native and sulfated TM3b fractions were determined using multi-angle laser light scattering and viscometry in 0.15M aq NaCl at 25 degrees C, respectively. The dependences of [eta] on Mw for TM3b and sulfated TM3b were found to be [eta]=0.18Mw(0.28+/-0.03) (Mw range from 3.30 x 10(4) to 3.90 x 10(7)) and [eta]=2.24 x 10(-2)Mw(0.52+/-0.06) (Mw range from 3.24 x 10(4) to 3.15 x 10(5)) in 0.15M aq NaCl at 25 degrees C, respectively. It revealed that both the native TM3b and its sulfated derivatives exist in a spherical chain conformation in 0.15M aq NaCl. Furthermore, the native and sulfated TM3b fractions showed potent antitumor activities in vivo and in vitro. The sulfated derivatives exhibited relatively higher in vitro antitumor activity against human hepatic cancer cell line HepG2 than the native TM3b. Water solubility and introduction of sulfate groups were the main factors in enhancing the antitumor activities.

A water-insoluble (1→3)-α- d -glucan (wc-PCM3-I) was isolated from the Poria cocos mycelia by extracting with 0.5 M NaOH aqueous solution at room temperature. wc-PCM3-I dissolved in dimethylsulfoxide (DMSO) containing 0.25 M LiCl was fractionated by a nonsolvent addition method into 10 fractions, and the solution properties of seven of them were studied by size exclusion chromatography combined with laser light scattering and viscometry at 25 °C. The dependences of intrinsic viscosity [η] and radius of gyration 〈s2〉z1/2 on weight-average molecular mass Mw for this glucan were found to be [η]=(9.77±0.1)×10−3Mw0.77±0.02 (cm3 g−1) and 〈s2〉z1/2=(1.83±0.4)×10−2Mw0.58±0.04 (nm) in the range of Mw from 4.16 to 29.0×104. On the basis of current theories for wormlike chain model, the conformation parameters of wc-PCM3-I were calculated to be 690 (nm−1) for molar mass per unit contour length (ML), 4.5 (nm) for persistence length (q), and 11.9 for characteristic ratio (C∞), suggesting that the (1→3)-α- d -glucan exists as a relatively extended flexible chain in the 0.25 M LiCl/DMSO solution.