Electrotaxis of alveolar epithelial cells in direct-current electric fields.

PURPOSE: This study aims to elucidate the electrotaxis response of alveolar epithelial cells (AECs) in direct-current electric fields (EFs), explore the impact of EFs on the cell fate of AECs, and lay the foundation for future exploitation of EFs for the treatment of acute lung injury. METHODS: AECs were extracted from rat lung tissues using magnetic-activated cell sorting. To elucidate the electrotaxis responses of AECs, different voltages of EFs (0, 50, 100, and 200 mV/mm) were applied to two types of AECs, respectively. Cell migrations were recorded and trajectories were pooled to better demonstrate cellular activities through graphs. Cell directionality was calculated as the cosine value of the angle formed by the EF vector and cell migration. To further demonstrate the impact of EFs on the pulmonary tissue, the human bronchial epithelial cells transformed with Ad12-SV40 2B (BEAS-2B cells) were obtained and experimented under the same conditions as AECs. To determine the influence on cell fate, cells underwent electric stimulation were collected to perform Western blot analysis. RESULTS: The successful separation and culturing of AECs were confirmed through immunofluorescence staining. Compared with the control, AECs in EFs demonstrated a significant directionality in a voltage-dependent way. In general, type Ⅰ alveolar epithelial cells migrated faster than type Ⅱ alveolar epithelial cells, and under EFs, these two types of cells exhibited different response threshold. For type Ⅱ alveolar epithelial cells, only EFs at 200 mV/mm resulted a significant difference to the velocity, whereas for, EFs at both 100 mV/mm and 200 mV/mm gave rise to a significant difference. Western blotting suggested that EFs led to an increased expression of a AKT and myeloid leukemia 1 and a decreased expression of Bcl-2-associated X protein and Bcl-2-like protein 11. CONCLUSION: EFs could guide and accelerate the directional migration of AECs and exert antiapoptotic effects, which indicated that EFs are important biophysical signals in the re-epithelialization of alveolar epithelium in lung injury.

Continuous purification and culture of rat type 1 and type 2 alveolar epithelial cells by magnetic cell sorting.

PURPOSE: The incidence of acute lung injury (ALI) in severe trauma patients is 48% and the mortality rate following acute respiratory distress syndrome evolved from ALI is up to 68.5%. Alveolar epithelial type 1 cells (AEC1s) and type 2 cells (AEC2s) are the key cells in the repair of injured lungs as well as fetal lung development. Therefore, the purification and culture of AEC1s and AEC2s play an important role in the research of repair and regeneration of lung tissue. METHODS: Sprague-Dawley rats (3-4 weeks, 120-150 g) were purchased for experiment. Dispase and DNase I were jointly used to digest lung tissue to obtain a single-cell suspension of whole lung cells, and then magnetic bead cell sorting was performed to isolate T1α positive cells as AEC1s from the single-cell suspension by using polyclonal rabbit anti-T1a (a specific AEC1s membrane protein) antibodies combined with anti-rabbit IgG microbeads. Afterwards, alveolar epithelial cell membrane marker protein EpCAM was designed as a key label to sort AEC2s from the remaining T1α-neg cells by another positive immunomagnetic selection using monoclonal mouse anti-EpCAM antibodies and anti-mouse IgG microbeads. Cell purity was identified by immunofluorescence staining and flow cytometry. RESULTS: The purity of AEC1s and AEC2s was 88.3% ± 3.8% and 92.6% ± 2.7%, respectively. The cell growth was observed as follows: AEC1s stretched within the 12-16 h, but the cells proliferated slowly; while AEC2s began to stretch after 24 h and proliferated rapidly from the 2nd day and began to differentiate after 3 days. CONCLUSION: AEC1s and AEC2s sorted by this method have high purity and good viability. Therefore, our method provides a new approach for the isolation and culture of AEC1s and AEC2s as well as a new strategy for the research of lung repair and regeneration.

[Effect of modified Danggui Shaoyao Powder on SOCS3/TLR4 signaling pathway in rats with chronic atrophic gastritis].

This study aims to investigate the effect of modified Danggui Shaoyao Powder on the suppressor of cytokine signaling 3(SOCS3)/Toll-like receptor 4(TLR4) signaling pathway in gastric tissue of rats with chronic atrophic gastritis(CAG).Sixty SPF-grade SD rats were randomly assigned into the normal group, model group, Moluo Pills group, and high-, medium-, and low-dose groups of modified Danggui Shaoyao Powder.The rats in other groups except the normal group were treated with N-methyl-N'-nitro-N-nitrosoguanidine(MNNG) to establish the CAG model.After 12 weeks of modeling, the rats in each group were administrated with corresponding drugs by gavage for 8 weeks.After the last administration, the histopathological changes of rat gastric mucosa were observed via hematoxylin-eosin(HE) staining.The serum levels of IL-6, TNF-α, and CRP were determined by enzyme-linked immunosorbent assay(ELISA).The mRNA levels of SOCS3 and TLR4 were determined by real-time PCR.The protein levels of SOCS3, TLR4, JAK2, p-JAK2, STAT3, and p-STAT3 in rat gastric tissue were measured by Western blot.Immunohistochemical method was employed to determine the protein levels of NF-κB, MyD88, NLRP3, Bcl-2, Bax, and Bad in rat gastric tissue.The results showed that modified Danggui Shaoyao Powder alleviated gastric mucosal atrophy of rats, significantly lowered the levels of IL-6, TNF-α, and CRP in rat serum, up-regulated the mRNA level of SOCS3, and down-regulated the mRNA level of TLR4 in rat gastric tissue.Furthermore, modified Danggui Shaoyao Powder up-regulated the protein level of SOCS3, down-regulated the protein levels of TLR4, p-JAK2, p-STAT3, NF-κB, MyD88, NLRP3, Bax, and Bad, and promoted the expression of Bcl-2 protein.Therefore, modified Danggui Shaoyao Powder may mitigate the gastric mucosal atrophy of rats by regulating the SOCS3/TLR4 signaling pathway.

Value of lung ultrasound score for evaluation of blast lung injury in goats.

PURPOSE: To establish a severe blast lung injury model of goats and investigate the feasibility of lung ultrasonic score in the evaluation of blast lung injury. METHODS: Twenty female healthy goats were randomly divided into three groups by different driving pressures: 4.0 MPa group (n = 4), 4.5 MPa group (n = 12) and 5.0 MPa group (n = 4). The severe blast lung injury model of goats was established using a BST-I bio-shock tube. Vital signs (respiration, heart rate and blood pressure), lung ultrasound score (LUS), PO2/FiO2 and extravascular lung water (EVLW) were measured before injury (0 h) and at 0.5 h, 3 h, 6 h, 9 h, 12 h after injury. Computed tomography scan was performed before injury (0 h) and at 12 h after injury for dynamic monitoring of blast lung injury and measurement of lung volume. The correlation of LUS with PaO2/FiO2, EVLW, and lung injury ratio (lesion volume/total lung volume*100%) was analyzed. All animals were sacrificed at 12 h after injury for gross observation of lung injury and histopathological examination. Statistical analysis was performed by the SPSS 22.0 software. The measurement data were expressed as mean ± standard deviation. The means of two samples were compared using independent-sample t-test. Pearson correlation analysis was conducted. RESULTS: (1) At 12 h after injury, the mortality of goats was 0, 41.67% and 100% in the 4.0 Mpa, 4.5 MPa and 5.0 MPa groups, respectively; the area of pulmonary hemorrhage was 20.00% ± 13.14% in the 4.0 Mpa group and 42.14% ± 15.33% in the 4.5 MPa group. A severe lung shock injury model was established under the driving pressure of 4.5 MPa. (2) The respiratory rate, heart rate, LUS and EVLW were significantly increased, while PaO2/FiO2 was significantly reduced immediately after injury, and then they gradually recovered and became stabilized at 3 h after injury. (3) LUS was positively correlated with EVLW (3 h: r = 0.597, 6 h: r = 0.698, 9 h: r = 0.729; p < 0.05) and lung injury ratio (12 h: r = 0.884, p < 0.05), negatively correlated with PaO2/FiO2 (3 h: r = -0.871, 6 h: r = -0.637, 9 h: r = -0.658; p < 0.05). CONCLUSION: We established a severe blast lung injury model of goats using the BST-I bio-shock tube under the driving pressure of 4.5 MPa and confirmed that ultrasound can be used for quick evaluation and dynamic monitoring of blast lung injury.

Secondary Metabolites and PI3K Inhibitory Activity of Colletotrichum gloeosporioides, a Fungal Endophyte of Uncaria rhynchophylla.

In the present study, nine compounds (1-9) were isolated from Colletotrichum gloeosporioides (an endophytic fungus from Uncaria rhynchophylla) which was cultured in wheat bran medium. Their structures were elucidated as 4-Epi-14-hydroxy-10, 23-dihydro-24, 25-dehydroaflavinine (1), 10, 23-Dihydro-24,25 -dehydro-21-oxoaflavinine (2), Ergosterol (3), Ergosterol peroxide (4), Mellein (5), 4, 5-dihydroblumenol A (6), Colletotrichine A (7), Cyclo(L-leucyl-L-leucyl) (8), and Brevianamide F (9) based on NMR spectral data, as well as comparing with previous literature data. This is the first report about the isolation of compounds 1-2, 6, and 8-9 from Colletotrichum genus. All compounds were tested for their phosphoinositide 3-kinase (PI3Kα) inhibitory activity. Compounds 8 and 9 showed potent PI3K α inhibitory activity with IC50 values of 38.1 and 4.8 µM, respectively, while the other compounds showed very weak activity at a concentration of 20 µg/mL.

[Effect of fresh Gastrodia elata on gut microbiota in mice].

Gastrodia elata B1.,a traditional Chinese medicine,was frequently applied as a cure for headache or migraine. Its effects include suppressing hyperactive liver,calming endogenous wind,dredging collateralsand relieving spasm. There has been a proportion that G. elata should be added to The List of Substances That Are Traditionally Both Food and Chinese Medicinal Materials. The dry G. elata was commonly used in clinic,which have some fundamental study on efficacy and mechanism. However,fresh G. elata,which was added to herbal cuisine very often,lacks corresponding research. The interaction of diet,microbiota and human is a hot issue and lots of scholars are focusing on it. This research sequenced the 16 S rRNA of mouse cecal contents on Mi Seq platform to understand the effect of taking fresh G. elata. As the results showing,multiple probiotics grew after taking fresh G. elata extract,including Ruminiclostridium,Butyricicoccus,and Parvibacter. To contrast,some pathogens or potential pathogens,such as Escherichia/Shigella,Parasutterella,decreased. This manifests that fresh G. elata performs a positive regulation on mouse gut microbiota,especially the low-dose fresh G. elata extraction could restructure the microbiota apparently. Our result reveals that microbiota might be a new target for G. elata extract and provides an important basis for further research on the interaction between gut microbiota and pharmacological activity of G. elata.

Correlation between pre-procedural plaque morphology and patterns of in-stent neointimal hyperplasia at 1-year follow-up in patients treated with new-generation drug-eluting stents: An optical coherence tomography based analysis.

INSTRUCTION: Several factors affect the in-stent intimal healing process after drug-eluting stents (DESs) implantation. We hope to investigate the influence of plaque characteristics on subsequent heterogeneous neointimal hyperplasia (NIH) using optical coherence tomography (OCT). METHODS: The study population consisted 217 patients with single-vessel de novo lesions who underwent both pre-procedural OCT scan and 12-month follow-up OCT examination. NIH is defined as at least five consecutive cross-sectional images with no less than 100µm neointimal thickness. According to OCT follow-up, patients were divided into three groups: neointima-covered group, homogeneous, and heterogeneous NIH group. RESULTS: 102 patients were categorized in neointima-covered group, 91 and 24 patients in homogeneous and heterogeneous group, respectively. Time interval between OCT scans was similar (P = 0.55). No significant differences in the patients' age, gender, comorbidities, laboratory findings, procedural, and lesion-related findings were found among these three groups. Heterogeneous group tended to have more subjects presented as acute coronary syndrome (ACS) (P = 0.04) and mean macrophage grade was higher in this group (P = 0.01). While no statistically significant difference concerning mean intimal thickness (P = 0.21) or neointimal burden (P = 0.73) was found between homogeneous and heterogeneous group. Multivariate logistic regression analysis showed that mean macrophage grade (OR: 2.26, 95%CI: 1.12 to 4.53, P = 0.02) and initial clinical presentation of ACS (OR: 2.81, 95%CI: 1.03 to 7.72, P = 0.04) were significant independent risk factors for heterogeneous NIH. CONCLUSION: Mean macrophage grade measured by OCT as a semi-quantitative morphological risk factor, as well as clinical presentation of ACS, was associated with in-stent neointimal heterogeneity after DES implantation.

The pollution characteristics of PM2.5 and correlation analysis with meteorological parameters in Xinxiang during the Shanghai Cooperation Organization Prime Ministers' Meeting.

The pollution characteristics of PM2.5 and correlation analysis with meteorological parameters in Xinxiang during the Shanghai Cooperation Organization Prime Ministers' Meeting were investigated. During the whole meeting, nine PM2.5 samples were collected at a suburban site of Xinxiang, and the average concentration of PM2.5 was 122.28 µg m-3. NO3-, NH4+, SO42- accounted for 56.8% of the total water-soluble ions. In addition, with an exception of Cl-, all of water-soluble ions decreased during the meeting. Total concentrations of crustal elements ranged from 6.53 to 185.86 µg m-3, with an average concentration of 52.51 µg m-3, which accounted for 82.5% of total elements. The concentrations of organic carbon and elemental carbon were 7.71 and 1.52 µg m-3, respectively, lower than those before and after the meeting. It is indicated that during the meeting, limiting motor vehicles is to reduce exhaust emissions, delay heating is to reduce the fossil fuel combustion, and other measures are to reduce the concentration of PM2.5. The directly dispersing by mixing layer height increase and the indirectly reducing the formation of secondary aerosol by low relative humidity, and these are the only two key removing mechanisms of PM2.5 in Xinxiang during the meeting.

[Pharmacodynamic evaluation and molecular mechanism research of Huanshao capsule on irregular menstruation].

Huanshao capsule is widely used in irregular menstruation and has achieved a good effect. Huanshao capsule can promote gonad development in mice, significantly improve the ovarian index in mice, increase estrogen level and reduce FSH level in rats, inhibit the pain response induced by oxytocin and estrogen, inhibit writhing reaction induced by acetic acid pain in mice. Due to the complexity of traditional Chinese medical formula, the pharmacological mechanism of the treatment on the irregular menstruation of the Huanshao capsule is unclear. In this study, the internet-based computation platform (www.tcmip.cn）was used to explore the molecular mechanism of Huanshao capsule on the menstrual. The aim of this study was to find the molecular mechanism of Huanshao capsule in treating menstrual. In the study of the molecular mechanism of Huanshao capsule in the treatment of menstrual by using the internet-based computation platform, Huanshao capsule maybe treat the menstrual by the pathway of endocrine system, GnRH signal transduction pathway, estrogen signal transduction pathway, oxytocin signaling pathway, thyroid hormone signaling pathway, VEGF signaling pathway, FCεRI signaling pathway and purine metabolism and nucleotide metabolism. The early pharmacological study confirmed Huanshao capsule could increase the serum estradiol level and decrease follicle stimulating hormone level and the traditional Chinese medicine pharmacology coincide with the prediction result of internet-based computation platform which roles as the pathway of GnRH signaling pathway and estrogen signal transduction pathway. Other pathway needs further experimental verification.

[Comparative pharmacodynamics study on Paris forrestii and pharmacopoeial Paridis Rhizoma].

Paris is a raw material of a variety of Chinese medicines, which has become deficient in resource due to market demand substantial growth and wild Paris resources reducing increasingly and the artificial cultivation slow growth. This study compared pharmacological activity in analgesia and anti-inflammatory and hemostasis effects of P. forrestii with pharmacopoeial Paridis Rhizoma to expand its range of Paris medicinal resources and protect wild resources of Paris and meet market demand. The experimental study showed that P. forrestii and P. polyphylla var. yunnanensis and P. polyphylla var. chinensis had analgesic, anti-inflammatory and hemostatic effects. They can significantly reduce the number of writhing and inhibit rat foot swelling induced by carrageenan and mice capillary permeability induced by acetic acid and short the bleeding time and clotting time. Their function is equivalent.

[Pharmacodynamics study on Paris vietnamensis].

Paris is commonly used in traditional Chinese medicine and its resource is in shortage, a variety of related plants are acquired as Paris. This study compared pharmacological activity in anti-inflammatory and hemostatic and blood rheology of P. vietnamensis with pharmacopoeial Paridis Rhizoma to expand its range of Paris medicinal resources and protect wild resources of Paris and meet market demand. The experimental study showed that P. vietnamensis and P. polyphylla var. yunnanensis and P. polyphylla var. chinensis had anti-inflammatory and hemostatic effect and improved blood rheolog. They can significantly inhibit rat foot swelling induced by carrageenan and short the bleeding time and clotting time and reduce the blood viscosity in rats with acute blood stasis model, P. vietnamensis and P. polyphylla var. yunnanensis can inhibit mice capillary permeability induced by acetic acid.

The cellular kinetics of lung alveolar epithelial cells and its relationship with lung tissue repair after acute lung injury.

BACKGROUND: Organ regeneration in mammals is hypothesized to require a functional pool of stem or progenitor cells, but the role of these cells in lung regeneration is unknown. METHODS: Based on the fact that postnatal regeneration of alveolar tissue has been attributed to alveolar epithelial cells, we established a hemorrhagic shock and Lipopolysaccharide (LPS) lung injury model. Using this model, we analyzed the cellular kinetics of lung alveolar epithelial cells. RESULTS: The results showed that alveolar epithelium type 2 cells (AEC2s) are damage resistant during acute lung injury, they might be the main cells involved in lung injury and repair. Then we observed the relationship between the expression of HGF, c-Met following ALI in rat lung and proliferation of AEC2s. The proliferation of AEC2s was inhibited when isolated primary AEC2s were co-cultured with c-Met inhibitor SU11274. Furthermore, the numbers of AEC2s was significantly decreased when ALI rats were administrated with SU11274 in vivo. It provided further evidence that the HGF/c-Met signaling plays a vital role in ALI-induced AEC2s proliferation. CONCLUSIONS: AEC2s are damage resistant during acute lung injury and the HGF/c-Met signaling pathway is of vital importance in the proliferation of AEC2s after ALI.

Isolation of lung multipotent stem cells using a novel microfluidic magnetic activated cell sorting system.

In recent years, more and more research has shown that the lung is an organ of regenerative potential, with several types of stem/progenitor cells undergoing proliferation and differentiation after lung injury and participating the injury repair process. Mouse lung multipotent stem cells (MLSCs) have extensive self-renewal ability in culture and could differentiate into endothelial and lung epithelial (alveolar epithelial type 1, 2, and Clara) cells in vitro. But the research of MLSCs was limited due to its rarity. In this study, we introduced a novel microfluidic magnetic activated cell sorting system in the isolation of MLSCs. The sorted MLSCs had better viability and purity. They were identified by colony formation efficiency and differentiation ability and they have self-renewal and differentiation capacities, highlighting their stem cell properties.

Rs1800625 in the receptor for advanced glycation end products gene predisposes to sepsis and multiple organ dysfunction syndrome in patients with major trauma.

INTRODUCTION: The receptor for advanced glycation end products (RAGE) is a transmembrane receptor of the immunoglobulin superfamily, it plays pivotal roles in the pathogenesis of sepsis in several ways. Our previous study showed that rs1800625 (-429T/C) revealed a strong clinical relevance with sepsis morbidity rate and multiple organ dysfunction syndrome (MODS) in patients with major trauma. In this study, we enlarged the sample size, added two validation populations and examined the expression of RAGE on the surface of peripheral leukocytes to ex vivo lipopolysaccharide (LPS) stimulation in subjects with different genotypes. METHODS: Rs1800625 was genotyped using pyrosequencing in 837 Chinese Han patients with major trauma in Chongqing. We then validated the clinical relevance in 340 Zhejiang and 347 Yunnan patients. The expression of RAGE on the surface of peripheral blood mononuclear cells was measured by flow cytometric analysis. RESULTS: The results indicated that rs1800625 was significantly associated with sepsis morbidity rate and MODS in patients with major trauma in the Chongqing, Zhejiang and Yunnan districts. Patients with CC genotype had lower sepsis morbidity rate and MODS after major trauma. Furthermore, patients with CC genotype had significantly higher RAGE expression (P = 0.009). CONCLUSIONS: The rs1800625 polymorphism is a functional single nucleotide polymorphism and confers host susceptibility to sepsis and MODS in patients with major trauma.

Treating chronic atrophic gastritis: identifying sub-population based on real-world TCM electronic medical records.

Background and Objective: Chronic atrophic gastritis (CAG) is a complex chronic disease caused by multiple factors that frequently occurs disease in the clinic. The worldwide prevalence of CAG is high. Interestingly, clinical CAG patients often present with a variety of symptom phenotypes, which makes it more difficult for clinicians to treat. Therefore, there is an urgent need to improve our understanding of the complexity of the clinical CAG population, obtain more accurate disease subtypes, and explore the relationship between clinical symptoms and medication. Therefore, based on the integrated platform of complex networks and clinical research, we classified the collected patients with CAG according to their different clinical characteristics and conducted correlation analysis on the classification results to identify more accurate disease subtypes to aid in personalized clinical treatment. Method: Traditional Chinese medicine (TCM) offers an empirical understanding of the clinical subtypes of complicated disorders since TCM therapy is tailored to the patient's symptom profile. We gathered 6,253 TCM clinical electronic medical records (EMRs) from CAG patients and manually annotated, extracted, and preprocessed the data. A shared symptom-patient similarity network (PSN) was created. CAG patient subgroups were established, and their clinical features were determined through enrichment analysis employing community identification methods. Different clinical features of relevant subgroups were correlated based on effectiveness to identify symptom-botanical botanical drugs correspondence. Moreover, network pharmacology was employed to identify possible biological relationships between screened symptoms and medications and to identify various clinical and molecular aspects of the key subtypes using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Results: 5,132 patients were included in the study: 2,699 males (52.60%) and 2,433 females (47.41%). The population was divided into 176 modules. We selected the first 3 modules (M29, M3, and M0) to illustrate the characteristic phenotypes and genotypes of CAG disease subtypes. The M29 subgroup was characterized by gastric fullness disease and internal syndrome of turbidity and poison. The M3 subgroup was characterized by epigastric pain and disharmony between the liver and stomach. The M0 subgroup was characterized by epigastric pain and dampness-heat syndrome. In symptom analysis, The top symptoms for symptom improvement in all three subgroups were stomach pain, bloating, insomnia, poor appetite, and heartburn. However, the three groups were different. The M29 subgroup was more likely to have stomach distention, anorexia, and palpitations. Citrus medica, Solanum nigrum, Jiangcan, Shan ci mushrooms, and Dillon were the most popular botanical drugs. The M3 subgroup has a higher incidence of yellow urine, a bitter tongue, and stomachaches. Smilax glabra, Cyperus rotundus, Angelica sinensis, Conioselinum anthriscoides, and Paeonia lactiflora were the botanical drugs used. Vomiting, nausea, stomach pain, and appetite loss are common in the M0 subgroup. The primary medications are Scutellaria baicalensis, Smilax glabra, Picrorhiza kurroa, Lilium lancifolium, and Artemisia scoparia. Through GO and KEGG pathway analysis, We found that in the M29 subgroup, Citrus medica, Solanum nigrum, Jiangcan, Shan ci mushrooms, and Dillon may exert their therapeutic effects on the symptoms of gastric distension, anorexia, and palpitations by modulating apoptosis and NF-κB signaling pathways. In the M3 subgroup, Smilax glabra, Cyperus rotundus, Angelica sinensis, Conioselinum anthriscoides, and Paeonia lactiflora may be treated by NF-κB and JAK-STAT signaling pathway for the treatment of stomach pain, bitter mouth, and yellow urine. In the M0 subgroup, Scutellaria baicalensis, Smilax glabra, Picrorhiza kurroa, Lilium lancifolium, and Artemisia scoparia may exert their therapeutic effects on poor appetite, stomach pain, vomiting, and nausea through the PI3K-Akt signaling pathway. Conclusion: Based on PSN identification and community detection analysis, CAG population division can provide useful recommendations for clinical CAG treatment. This method is useful for CAG illness classification and genotyping investigations and can be used for other complicated chronic diseases.

Sepsis-induced immunosuppression: mechanisms, diagnosis and current treatment options.

Sepsis is a common complication of combat injuries and trauma, and is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. It is also one of the significant causes of death and increased health care costs in modern intensive care units. The use of antibiotics, fluid resuscitation, and organ support therapy have limited prognostic impact in patients with sepsis. Although its pathophysiology remains elusive, immunosuppression is now recognized as one of the major causes of septic death. Sepsis-induced immunosuppression is resulted from disruption of immune homeostasis. It is characterized by the release of anti-inflammatory cytokines, abnormal death of immune effector cells, hyperproliferation of immune suppressor cells, and expression of immune checkpoints. By targeting immunosuppression, especially with immune checkpoint inhibitors, preclinical studies have demonstrated the reversal of immunocyte dysfunctions and established host resistance. Here, we comprehensively discuss recent findings on the mechanisms, regulation and biomarkers of sepsis-induced immunosuppression and highlight their implications for developing effective strategies to treat patients with septic shock.

Occurrence and distribution of organochlorine pesticides (DDT and HCH) in sediments from the middle and lower reaches of the Yellow River, China.

Sediments used in this study were selected from 23 stations in the middle and lower reaches of the Yellow River and its tributaries in November 2005. The levels and distribution patterns of selected organochlorine pesticides (OCPs = p,p(')-DDT, o,p (')-DDT, p,p(')-DDE, p,p(')-DDD, alpha-, beta-, gamma-, and delta-HCH) in samples were investigated by analysis of gas chromatography coupled with micro-electronic capture detector. Concentration of OCPs in the sediments from the Yellow River ranged from 0.05 to 5.03 ng g(-1) (mean, 1.02 ng g(-1)) for summation operatorDDT, 0.09-12.89 ng g(-1) (mean, 1.08 ng g(-1)) for summation operatorHCH. The concentration distribution of summation operatorDDT and summation operatorHCH varied significantly with different sampling station, indicating their different contamination sources. Composition analyses demonstrated that residues of DDTs in sediments came from the previous inputs of organochlorine pesticides, while beta-HCH and gamma-HCH significantly dominated in the sediments for HCHs.

Optimal H2O2 preconditioning to improve bone marrow mesenchymal stem cells' engraftment in wound healing.

BACKGROUND: The transplantation of bone marrow mesenchymal stem cells (BMSCs) is a promising therapeutic strategy for wound healing. However, the poor migration capacity and low survival rate of transplanted BMSCs in wounds weaken their potential application. OBJECTIVE: To identify the optimal protocol for BMSCs preconditioned with H2O2 and improve the therapeutic efficacy using H2O2-preconditioned BMSCs in wound healing. METHODS: Mouse BMSCs were exposed to various concentrations of H2O2, and the key cellular functional properties were assessed to determine the optimal precondition with H2O2. The H2O2-preconditioned BMSCs were transplanted into mice with full-thickness excisional wounds to evaluate their healing capacity and tissue engraftment. RESULTS: Treatment BMSCs with 50 µM H2O2 for 12 h could significantly enhance their proliferation, migration, and survival by maximizing the upregulation of cyclin D1, SDF-1, and its receptors CXCR4/7 expressions, and activating the PI3K/Akt/mTOR pathway, but inhibiting the expression of p16 and GSK-3ß. Meanwhile, oxidative stress-induced BMSC apoptosis was also significantly attenuated by the same protocol pretreatment with a decreased ratio of Bax/Bcl-2 and cleaved caspase-9/3 expression. Moreover, after the identification of the optimal protocol of H2O2 precondition in vitro, the migration and tissue engraftment of transfused BMSCs with H2O2 preconditioning were dramatically increased into the wound site as compared to the un-preconditioned BMSCs. The increased microvessel density and the speedy closure of the wounds were observed after the transfusion of H2O2-preconditioned BMSCs. CONCLUSIONS: The findings suggested that 50 µM H2O2 pretreated for 12 h is the optimal precondition for the transplantation of BMSCs, which gives a considerable insight that this protocol may be served as a promising candidate for improving the therapeutic potential of BMSCs for wound healing.

Distribution of polycyclic aromatic hydrocarbons (PAHs) in Henan Reach of the Yellow River, Middle China.

The distribution and source of 16 polycyclic aromatic hydrocarbons (PAHs) in Henan Reach of the Yellow River, Middle China, has been investigated. summation sigmaPAHs levels ranged from 144.3 to 2361 ng L(-1) in water, from 506.6 to 10,510 ng g(-1) in suspended particulate matters (SPMs) and from 16.4 to 1358 ng g(-1) in sediment, respectively. The compositional profile of PAHs revealed that 2-3-ring PAHs were predominated in water and 2-4-ring PAHs were abundant in SPMs. Whereas the PAHs in sediment were composed mainly of 3-5-ring PAHs. The spatial distribution of PAHs indicated that concentrations of PAHs in water and SPMs in dry season were much higher than those in flooding season. It may be attributed to a high flow rate in flooding season. The ratios of phenanthrene/anthracene (Phe/Ant) and fluoranthene/pyrene (Flua/Pyr) reflected a pattern of pyrogenic input. The potential ecosystem risk assessment indicated that the ecosystem risk of PAHs was relatively low in Henan Reach of the Yellow River.

Decolorization of an azo dye Orange G in aqueous solution by Fenton oxidation process: effect of system parameters and kinetic study.

To establish cost-efficient operating conditions for potential application of Fenton oxidation process to treat wastewater containing an azo dye Orange G (OG), some important operating parameters such as pH value of solutions, dosages of H(2)O(2) and Fe(2+), temperature, presence/absence of chloride ion and concentration of the dye, which effect on the decolorization of OG in aqueous solution by Fenton oxidation have been investigated systematically. In addition, the decolorization kinetics of OG was also elucidated based on the experimental data. The results showed that a suitable decolorization condition was selected as initial pH 4.0, H(2)O(2) dosage 1.0 x 10(-2)M and molar ratio of [H(2)O(2)]/[Fe(2+)] 286:1. The decolorization of OG enhanced with the increasing of reaction temperature but decreased as a presence of chloride ion. On the given conditions, for 2.21 x 10(-5) to 1.11 x 10(-4)M of OG, the decolorization efficiencies within 60 min were more than 94.6%. The decolorization kinetics of OG by Fenton oxidation process followed the second-order reaction kinetics, and the apparent activation energy E, was detected to be 34.84 kJ mol(-1). The results can provide fundamental knowledge for the treatment of wastewater containing OG and/or other azo dyes by Fenton oxidation process.