Valproic acid accelerates skin wound healing in mice via its anti-inflammatory and apoptotic cell clearance-promoting effects.

OBJECTIVE: To investigate the effects of valproic acid (VPA) on skin wound healing in mice. METHODS: Full-thickness wounds were created in mice, and then VPA was applied. The wound areas were quantified daily. In the wounds, granulation tissue growth, epithelialization, collagen deposition, and the mRNA levels of inflammatory cytokines were measured; furthermore, apoptotic cells were labeled. In vitro, VPA was added to RAW 264.7 cells (macrophages) stimulated with lipopolysaccharide, and apoptotic Jurkat cells were cocultured with the VPA-pretreated macrophages. Then, phagocytosis was analyzed, and the mRNA levels of phagocytosis-associated molecules and inflammatory cytokines were measured in the macrophages. RESULTS: VPA application significantly accelerated wound closure, granulation tissue growth, collagen deposition, and epithelialization. In wounds, the levels of tumor necrosis factor-α, interleukin (IL)-6, and IL-1ß were decreased by VPA, whereas those of IL-10 and transforming growth factor-ß1 were increased. Additionally, VPA reduced the number of apoptotic cells. In vitro, VPA inhibited the inflammatory activation of macrophages and promoted the phagocytosis of apoptotic cells by macrophages. CONCLUSION: VPA accelerated skin wound healing, which could be partly attributable to its anti-inflammatory and apoptotic cell clearance-promoting effects, indicating that VPA could be a promising candidate for enhancing skin wound healing.

Biogas slurry purification-lettuce growth nexus: Nutrients absorption and pollutants removal.

As a main by-product of anaerobic digestion in biogas plants, biogas slurry contains a high concentration of mineral elements (such as ammonia­nitrogen and potassium) and chemical oxygen demand (COD). So determining how to dispose the biogas slurry in a harmless and value-added ways is crucial from the perspective of ecological and environmental protections. This study explored a novel nexus between biogas slurry and lettuce, in which the biogas slurry was concentrated and saturated with carbon dioxide (CO2) to serve as a hydroponic solution for lettuce growth. Meanwhile, the lettuce was used to purify the biogas slurry through removing pollutants. Results showed that when concentrating the biogas slurry, the total nitrogen and ammonia nitrogen contents in the biogas slurry decreased with the increase of concentration factor. The CO2-rich 5-time-concentrated biogas slurry (CR-5CBS) was screened as the most suitable hydroponic solution for lettuce growth after comprehensively considering the nutrient element balance, energy consumption of concentrating the biogas slurry and CO2 absorption performance. The quality of lettuce cultivated in CR-5CBS was comparable to that of the Hoagland-Arnon nutrient solution in terms of physiological toxicity, nutritional quality, and mineral uptake. Obviously, the hydroponic lettuce could effectively utilize the nutrients in CR-5CBS to purify CR-5CBS, meeting the standard of reclaimed water quality for agricultural reuse. Interestingly, when the same yield of lettuce is targeted, using CR-5CBS as the hydroponic solution to cultivate lettuce can save about US $151/m3-CR-5CBS for lettuce production compared to the Hoagland-Arnon nutrient solution. This study might provide a feasible method for high-value utilization and harmless disposal of biogas slurry.

Erythropoietin mediates re-programming of endotoxin-tolerant macrophages through PI3K/AKT signaling and protects mice against secondary infection.

Initial lipopolysaccharide (LPS) exposure leads to a hypo-responsive state by macrophages to a secondary stimulation of LPS, known as endotoxin tolerance. However, recent findings show that functions of endotoxin-tolerant macrophages are not completely suppressed, whereas they undergo a functional re-programming process with upregulation of a panel of molecules leading to enhanced protective functions including antimicrobial and tissue-remodeling activities. However, the underlying molecular mechanisms are still elusive. Erythropoietin (EPO), a glycoprotein regulated by hypoxia-inducible factor 1α (HIF-1α), exerts anti-inflammatory and tissue-protective activities. Nevertheless, the potential effects of EPO on functional re-programming of endotoxin-tolerant macrophages have not been investigated yet. Here, we found that initial LPS exposure led to upregulation of HIF-1α/EPO in macrophages and that EPO enhanced tolerance in tolerized macrophages and mice as demonstrated by suppressed proinflammatory genes such as Il1b, Il6, and Tnfa after secondary LPS stimulation. Moreover, we showed that EPO improved host protective genes in endotoxin-tolerant macrophages and mice, such as the anti-bacterial genes coding for cathelicidin-related antimicrobial peptide (Cnlp) and macrophage receptor with collagenous structure (Marco), and the tissue-repairing gene vascular endothelial growth factor C (Vegfc). Therefore, our findings indicate that EPO mediates the functional re-programming of endotoxin-tolerant macrophages. Mechanistically, we found that PI3K/AKT signaling contributed to EPO-mediated re-programming through upregulation of Irak3 and Wdr5 expression. Specifically, IL-1 receptor-associated kinase 3 (IRAK3) was responsible for inhibiting proinflammatory genes Il1b, Il6, and Tnfa in tolerized macrophages after LPS rechallenge, whereas WDR5 contributed to the upregulation of host beneficial genes including Cnlp, Marco, and Vegfc. In a septic model of mice, EPO pretreatment significantly promoted endotoxin-tolerant re-programming, alleviated lung injury, enhanced bacterial clearance, and decreased mortality in LPS-tolerized mice after secondary infection of Escherichia coli. Collectively, our results reveal a novel role for EPO in mediating functional re-programming of endotoxin-tolerant macrophages; thus, targeting EPO appears to be a new therapeutic option in sepsis and other inflammatory disorders.

Simultaneous biogas upgrading, CO2 sequestration, and biogas slurry decrement using biomass ash.

A novel system for simultaneous biogas upgrading, CO2 sequestration, and biogas slurry decrement was established by adding biomass ash into biogas slurry to form a renewable CO2 mixture absorbent. After CO2 saturation, the CO2-rich mixture absorbent could be applied for plant growth. When the mass ratio of liquid to solid was 4:1, CO2 absorption capacity of this mixture absorbent reached up to 97.33 g-CO2/kg-biomass-ash, which was about 135% higher than that of the biomass ash-water mixture. The highest value of 129.94 g-CO2/kg-biomass-ash was obtained at a liquid-solid ratio of 99:1. When the TS concentration of anaerobic digestion feedstock was higher than 16 wt% and the water content of CO2-rich absorbent was about 50 wt%, more than 80% of biogas slurry can be adsorbed by the biomass ash. If the biomass ash with a CO2 absorption capacity of 100 g-CO2/kg was adopted and its transportation distance was less than 45 km, the biogas upgrading cost could be lower than the global average level (about RMB¥ 0.7/Nm3-biogas) when using the novel system proposed in this study.

Erythropoietin Promotes Infection Resolution and Lowers Antibiotic Requirements in E. coli- and S. aureus-Initiated Infections.

Endogenous mechanisms underlying bacterial infection resolution are essential for the development of novel therapies for the treatment of inflammation caused by infection without unwanted side effects. Herein, we found that erythropoietin (EPO) promoted the resolution and enhanced antibiotic actions in Escherichia coli (E. coli)- and Staphylococcus aureus (S. aureus)-initiated infections. Levels of peritoneal EPO and macrophage erythropoietin receptor (EPOR) were elevated in self-limited E. coli-initiated peritonitis. Myeloid-specific EPOR-deficient mice exhibited an impaired inflammatory resolution and exogenous EPO enhanced this resolution in self-limited infections. Mechanistically, EPO increased macrophage clearance of bacteria via peroxisome proliferator-activated receptor γ (PPARγ)-induced CD36. Moreover, EPO ameliorated inflammation and increased the actions of ciprofloxacin and vancomycin in resolution-delayed E. coli- and S. aureus-initiated infections. Collectively, macrophage EPO signaling is temporally induced during infections. EPO is anti-phlogistic, increases engulfment, promotes infection resolution, and lowers antibiotic requirements.

A new approach for biogas slurry disposal by adopting CO2-rich biogas slurry as the flower fertilizer of Spathiphyllum: Feasibility, cost and environmental pollution potential.

A new approach for biogas slurry disposal was put forward in this study through converting biogas slurry to the organic fertilizer of Spathiphyllum. The biogas slurry was firstly concentrated by vacuum distillation to reduce its volume by 80% who is called 5CBS, and then CO2 saturated to reduce its pH to about 6.50 ± 0.20. With or without adding the exogenetic Ca, Mg and P nutrients, CO2-rich 5CBS (i.e., CR-5CBS) was adopted as the root or foliar fertilizer to cultivate Spathiphyllum. Additionally, the commercial Spathiphyllum fertilizer was also experimented as a control. Results showed that the cases adopting CR-5CBS as the root or foliar fertilizer can obtain the agronomic traits and ornamental values of Spathiphyllum better those irrigated by the commercial fertilizer. Exogenetic nutrients added into CR-5CBS can lead to a decreased dead leaf number of Spathiphyllum, an enhanced N assimilation performance, however only a slightly improved assimilation performance of Ca, Mg and P. In terms of the fertilizer economy, CR-5CBS without exogenetic nutrient addition may be a promising for replacing the commercial Spathiphyllum fertilizer in the future. Economic and environmental pollution potential (EPP) analyses indicated that treating biogas slurry as the organic flower fertilizer can achieve a high net profit with about $ 28.89/m3-biogas slurry and a negative EPP value (-3.9), showing its profitability and environmental friendliness.

[Acupoint Injection at "Yingxiang"(LI 20) and "Yintang"(GV 29) May Relieve Nasal Allergic Symptoms Possibly by Down-regulating Expression of Histamine Receptor H 1 and H 4 in Nasal Mucosa of Allergic Rhinitis Rats].

OBJECTIVE: To observe the effect of acupoint injection at "Yingxiang"(LI 20) and "Yintang"(GV 29) on nasal allergic reactions and the expression of histamine receptor H 1 and H 4 in nasal mucosa of allergic rhinitis (AR) rats, so as to reveal its mechanism underlying improvement of AR. METHODS: SD rats were randomized into normal, model, non-acupoint injection and acupoint injection groups (n=8 in each). The AR model was established by intraperitoneal (i.p.) injection of mixture of ovalbumin, aluminium hydroxide gel and normal saline (once every other day, for 7 times), and nasal drip of ovalbumin (on the following day of i.p.for 7 days). The mixture solution of lidocaine, dexamethasone (DXM) and transfer factor (0.1 mL/acupoint or non-acupoint) was injected into bilateral LI 20 and GV 29 in the acupoint injection group, or into the non-acupoints (about 5 cm below the armpit on both sides, and the middle point between the left "Houhai"[GV 1] and "Huantiao"[GB 30]), on the 1st , 5th, 9th, and 13th day after modeling. Symptoms of sneezing, nasal discharge, nose-rubbing, etc. were scored after the treatment. The expression levels of H1 R and H4 R proteins and genes in the nasal mucosa tissue were determined using immunohistochemistry and quantitative real-time PCR, respectively. RESULTS: Compared with the normal group, the symptom score and the expression levels of H1 R, H4 R proteins and genes in nasal mucosa were significantly increased in the model group (P<0.05). After acupoint injection for 4 times, the symptom score and the expression levels of H1 R, H4 R proteins and mRNAs were significantly down-regulated in the acupoint injection group relevant to the model group (P<0.05). There were no significant differences between the non-acupoint and the model groups in the abovementioned indexes (P>0.05), suggesting a specificity of the effect of acupoint injection. CONCLUSION: Acupoint injection can relieve the allergic symptoms of AR rats, which may be related to its effects in down-regulating the over expression of H1 R and H4 R proteins and genes in the nasal mucosa.

[Effect of Acupoint Injection on Eosinophil Counts,Protein and mRNA Expressions of Eotaxin in Nasal Mucosa of Allergic Rhinitis Rats].

OBJECTIVE: To observe the effect of acupoint injection on eosinophils (EOS) counts and expression of eotaxin in nasal mucosa of allergic rhinitis (AR) rats, so as to reveal its mechanism underlying improving AR. METHODS: Twenty-four Sprague-Dawley (SD) rats were randomly divided into normal, model and acupoint injection groups (n=8 in each group). The AR model was established by intraperitoneal injection of ovalbumin sensitization. Bilateral "Yingxiang"(LI 20) and "Yintang"(GV 29) were selected for acupoint injection of the mixture solution of lidocaine, dexamethasone, and transfer factor (0.1 mL/acupoint) on the 1st, 5th, 9th, and 13th day after AR model established, a total of four times. EOS in the nasal mucosa was counted under light microscope after HE staining. Protein and mRNA expressions of eotaxin in the nasal mucosa were detected by immunohistochemical and RT-PCR methods, respectively. RESULTS: Compared with the normal group, EOS counts, protein and mRNA expressions of eotaxin in the nasal mucosa were significantly higher in the model group (P<0.05). Compared with the model group, EOS counts, protein and mRNA expressions of eotaxin in the nasal mucosa were significantly lower in the acupoint injection group (P<0.05). CONCLUSIONS: Acupoint injection can reduce the nasal mucosa inflammation by suppressing the protein and mRNA expressions of eotaxin, decreasing the infiltration and gathering of EOS in the nasal mucosa.