Transferrin Is Up-Regulated by Microbes and Acts as a Negative Regulator of Immunity to Induce Intestinal Immunotolerance.

Cross-talks (e.g., host-driven iron withdrawal and microbial iron uptake between host gastrointestinal tract and commensal microbes) regulate immunotolerance and intestinal homeostasis. However, underlying mechanisms that regulate the cross-talks remain poorly understood. Here, we show that bacterial products up-regulate iron-transporter transferrin and transferrin acts as an immunosuppressor by interacting with cluster of differentiation 14 (CD14) to inhibit pattern recognition receptor (PRR) signaling and induce host immunotolerance. Decreased intestinal transferrin is found in germ-free mice and human patients with ulcerative colitis, which are characterized by impaired intestinal immunotolerance. Intestinal transferrin and host immunotolerance are returned to normal when germ-free mice get normal microbial commensalism, suggesting an association between microbial commensalism, transferrin, and host immunotolerance. Mouse colitis models show that transferrin shortage impairs host's tolerogenic responses, while its supplementation promotes immunotolerance. Designed peptide blocking transferrin-CD14 interaction inhibits immunosuppressive effects of transferrin. In monkeys with idiopathic chronic diarrhea, transferrin shows comparable or even better therapeutic effects than hydrocortisone. Our findings reveal that by up-regulating host transferrin to silence PRR signaling, commensal bacteria counteract immune activation induced by themselves to shape host immunity and contribute for intestinal tolerance.

Effect of moxibustion on knee joint stiffness characteristics in recreational athletes pre- and post-fatigue.

Objective: Joint stiffness results from the coupling of the nervous system and joint mechanics, and thus stiffness is a comprehensive representation of joint stability. It has been reported that moxibustion can alleviate general weakness and fatigue symptoms and subsequently may influence joint stiffness. This study investigated whether moxibustion could enhance knee joint stiffness in recreational athletes pre- and post-fatigue. Methods: Eighteen participants were randomized into intervention (5 males: 20.6 ± 1.5 yr; 4 females: 20.8 ± 1.5 yr) and control groups (5 males: 19.4 ± 0.9 yr; 4 females: 20.5 ± 0.6 yr). The intervention group received indirect moxibustion applied to acupoints ST36 (bilateral) and CV4 for 30 min every other day for 4 consecutive weeks. The control group maintained regular exercise without moxibustion. Peak torque (PT) of right knee extensor, relaxed and contracted muscle stiffness (MS) of vastus lateralis, and knee extensor musculoarticular stiffness (MAS) was assessed with an isokinetic dynamometer (IsoMed 2000), myometer, and free oscillation technique, respectively. Measurements were taken at three time points: pre-intervention, post-intervention/pre-fatigue, and post-fatigue. Results: MAS (P = 0.006) and PT (P = 0.007) in the intervention group increased more from pre-to post-intervention compared with the control group. Post-fatigue MAS (P = 0.016) and PT (P = 0.031) increased more in the intervention group than in the control group. Conclusion: Moxibustion enhanced PT and knee MAS, suggesting that this intervention could be used in injury prevention and benefit fatigue resistance in young recreational athletes.

Treatment of distiller grain with wet-process phosphoric acid leads to biochar for the sustained release of nutrients and adsorption of Cr(VI).

Soil amendment products, such as biochar, with both sustained nutrient release and heavy metal retention properties are of great need in agricultural and environmental industries. Herein, we successfully prepared a new biochar material with multinutrient sustained-release characteristics and chromium removal potential derived from distiller grain by wet-process phosphoric acid (WPPA) modification without washing. SEM, TEM TG-IR, in situ DRIFTS and XRD characterization indicated that biochar and polyphosphate formed simultaneously and were tightly intertwined by one-step pyrolysis. The optimal product (PKBC-400) had the most stable carbon structure and an adequate P-O-P structure with less P loss. Batch experiments illustrated that 92.83% P (ortho-P), 85.94% K, 41.49% Fe, 78.42% Al and 65.60% Mg were continuously released in water from PKBC-400 within 63 days, and the maximum Cr removal rate reached 83.57% (50 mg/L K2Cr2O7, pH=3.0) with an increased BET surface area (304.0557 m2/g) after nutrient release. SEM, IC and 31P NMR analyses revealed that the dissolution and hydrolysis of polyphosphates not only realized the sustained release of multiple nutrients but also significantly improved the sustained release performance. The proposed resource utilization strategy provided new ideas for Cr hazard control, biomass waste utilization and fertilizer development.

Selective adsorption of various phosphorus species coexistence in water-soluble ammonium polyphosphate on goethite: Experimental investigation and molecular dynamics simulation.

The geochemical processes of polyphosphates (poly-Ps) are important for phosphorus (P) management and environmental protection. Water-soluble ammonium polyphosphate (APP) containing various P species has been increasingly used as an alternative P-fertilizer. The various P species coexistence and the chelation of poly-Ps with mental would trigger the P's competitive adsorption and affect the APP's adsorption intensity on goethite, compared to single orthophosphate (P1). P adsorption behaviors of APP1 with two P species and APP2 with seven P species on goethite were investigated via batch experiments in comparison to the traditional P-fertilizer of mono-ammonium phosphate (MAP). Coadsorption of P1 and pyrophosphate (P2) on goethite was investigated by molecular dynamics (MD) simulation. The more Fe3+ dissolved from goethite as a bridge due to the chelation of poly-Ps in APP and contributed to the stronger APP adsorption on goethite compared with MAP. Ion chromatography and spectral analysis showed P1 and P2 in APP were mainly adsorbed by goethite via mainly forming bidentate complexes. The goethite preferentially adsorbed P1 at lower APP concentration but increased the poly-Ps' adsorption at higher APP concentration. MD simulation showed that electrostatic interaction and hydrogen bonds played a key role in water-phosphates-goethite systems. The P1 pre-adsorbed on goethite could be replaced by P2 at high P2 concentration. The results develop new insights regarding the selective adsorption of various P species coexistence in goethite-rich environments.

Chemical modifications to increase the therapeutic potential of antimicrobial peptides.

The continued use of antibiotics has been accompanied by the rapid emergence and spread of antibiotic-resistant strains of bacteria. Antimicrobial peptides (AMPs), also known as host defense peptides, show multiple features as an ideal antimicrobial agent, including potent, rapid, and broad-spectrum antimicrobial activity, low promotion of antimicrobial resistance, potent anti-biofilm activity, and lethality against metabolically inactive microorganisms. However, several crucial drawbacks constrain the use of AMPs as clinical drugs, e.g., liability in vivo, toxicity when used systemically, and high production costs. Based on recent findings and our own experiences, here we summarize some chemical modifications and key design strategies to increase the therapeutic potential of AMPs, including 1) enhancing antimicrobial activities, 2) improving in vivo effectiveness, and 3) reduction in toxicity, which may facilitate the design and optimization of AMPs for the development of drug candidates. We also discuss the present challenges in the optimization of AMPs and future concerns about the resistance and cross-resistance to AMPs in the development of AMPs as therapeutic drugs.

A Designed Tryptophan- and Lysine/Arginine-Rich Antimicrobial Peptide with Therapeutic Potential for Clinical Antibiotic-Resistant Candida albicans Vaginitis.

New therapeutic agents for Candida albicans vaginitis are urgently awaiting to be developed because of the increasing antibiotic resistance of C. albicans. Antimicrobial peptides (AMPs) are one of the most promising choices for next-generation antibiotics. In this study, novel peptides were designed based on snake venom antimicrobial peptide cathelicidin-BF to promote anti-C. albicans activity and decrease side-effects. The designing strategies include substitutions of charged or hydrophobic amino acid residues for noncharged polar residues to promote antimicrobial activity and insertion of a hydrophobic residue in the hydrophilic side of the helix structure to reduce hemolysis. A designed tryptophan and lysine/arginine-rich cationic peptide 4 (ZY13) (VKRWKKWRWKWKKWV-NH2) exhibited excellent antimicrobial activity against either common strain or clinical isolates of antibiotic-resistant C. albicans with little hemolysis. Peptide 4 showed significant therapeutic effects on vaginitis in mice induced by the infection of clinical antibiotic-resistant C. albicans. The approaches herein might be useful for designing of AMPs.

YY-39, a tick anti-thrombosis peptide containing RGD domain.

Ticks are obligatory blood feeding ectoparasites, which continuously attach to their hosts for 1-2 weeks. There are many biologically active compounds in tick salivary glands interfering host haemostatic system and to successfully obtain blood meal. Several platelet aggregation inhibitors have been identified from ticks. A family of conserved peptides, which were identified from transcriptome analysis of many tick salivary glands, were found to contain unique primary structure including predicted mature peptides of 39-47 amino acid residues in length and a Pro/Glu(P/E)-Pro/His(P/H)-Lys-Gly-Asp(RGD) domain. Given their unique structure and RGD domain, they are considered a novel family of disintegrins that inhibit platelet aggregation. One of them (YY-39) was tested for its effects on platelets and thrombosis in vivo. YY-39 was found effectively to inhibit platelet aggregation induced by adenosine diphosphate (ADP), thrombin and thromboxane A2 (TXA2). Furthermore, YY-39 blocked platelet adhesion to soluble collagen and bound to purified GPIIb/IIIa in a dose-dependent manner. In in vivo experiments, YY-39 reduced thrombus weight effectively in a rat arteriovenous shunt model and inhibited thrombosis in a carrageenan-induced mouse tail thrombosis model. Combined with their prevalence in ticks and platelet inhibitory functions, this family of peptides might be conserved tick anti-haemostatic molecules.

Simultaneous determination of five anthraquinones in a Chinese traditional preparation by RP-HPLC using an improved extraction procedure.

OBJECTIVE: The stable quality of Chinese herbal medicines is a critical factor for their reliable clinical efficiency. An improved liquid-liquid extraction procedure and a liquid chromatographic method were developed to simultaneously analyze five anthraquinones (aloe-emodin, rhein, emodin, chrysophanol and physcion) in a Chinese traditional hospital preparation, Fuyankang mixture, in order to quantitatively control its quality in a more effective way. METHODS: A more economical and repeatable extraction procedure based on conventional liquid-liquid extraction technique was developed and used to extract five marker components in Fuyankang mixture. These anthraquinones were separated in less than 20 min on a C18 column with methanol and 0.1% phosphoric acid (88:12, v/v) as mobile phase. The method was validated for specificity, precision, spiked recovery and stability. RESULTS: Compared to conventional liquid-liquid extraction, the improved liquid-liquid extraction was found to be more effective for simultaneous extraction of anthraquinones from an aqueous Chinese herbal preparation, especially for hydrophobic compounds. The improved extraction method was successfully applied to determine the content of five marker components in Fuyankang mixture by the means of reverse phase high-performance liquid chromatography. CONCLUSION: The improved extraction procedure may be suitable for routine quality control of Fuyankang mixture and other traditional preparations at city-level hospitals in China.

Cathelicidin-BF, a snake cathelicidin-derived antimicrobial peptide, could be an excellent therapeutic agent for acne vulgaris.

Cathelicidins are a family of antimicrobial peptides acting as multifunctional effector molecules in innate immunity. Cathelicidin-BF has been purified from the snake venoms of Bungarus fasciatus and it is the first identified cathelicidin antimicrobial peptide in reptiles. In this study, cathelicidin-BF was found exerting strong antibacterial activities against Propionibacterium acnes. Its minimal inhibitory concentration against two strains of P. acnes was 4.7 µg/ml. Cathelicidin-BF also effectively killed other microorganisms including Staphylococcus epidermidis, which was possible pathogen for acne vulgaris. Cathelicidin-BF significantly inhibited pro-inflammatory factors secretion in human monocytic cells and P. acnes-induced O2.- production of human HaCaT keratinocyte cells. Observed by scanning electron microscopy, the surfaces of the treated pathogens underwent obvious morphological changes compared with the untreated controls, suggesting that this antimicrobial peptide exerts its action by disrupting membranes of microorganisms. The efficacy of cathelicidin-BF gel topical administering was evaluated in experimental mice skin colonization model. In vivo anti-inflammatory effects of cathelicidin-BF were confirmed by relieving P. acnes-induced mice ear swelling and granulomatous inflammation. The anti-inflammatory effects combined with potent antimicrobial activities and O2.- production inhibition activities of cathelicidin-BF indicate its potential as a novel therapeutic option for acne vulgaris.