Jujuboside B alleviates acetaminophen-induced hepatotoxicity in mice by regulating Nrf2-STING signaling pathway.

BACKGROUND: Jujuboside B (JuB) is the main bioactive saponin component of Chinese anti-insomnia herbal medicine Ziziphi Spinosae Semen, which has been reported to possess varied pharmacological functions. Even though it has been traditionally used to treat inflammation- and toxicity-related diseases, the effects of JuB on acetaminophen (APAP) overdose-induced hepatotoxicity have not been determined yet. METHODS: C57BL/6 J mice were pre-treated with JuB (20 or 40 mg/kg) for seven days before APAP (400 mg/kg) injection. After 24 h of APAP treatment, serum, and liver tissues were collected to evaluate the therapeutic effects. To investigate whether the Nrf2-STING signaling pathway is involved in the protective effects of JuB against APAP-induced hepatotoxicity, the mice received the DMXAA (the specific STING agonist) or ML385 (the specific Nrf2 inhibitor) during the administration of JuB, and Hematoxylin-eosin staining, Real-time PCR, immunohistochemical, and western blot were performed. RESULTS: JuB pretreatment reversed APAP-induced CYP2E1 accumulations and alleviated APAP-induced acute liver injury. Furthermore, JuB treatment significantly inhibited oxidative stress and the pro-inflammatory cytokines, as well as alleviated hepatocyte apoptosis induced by APAP. Besides, our result also demonstrated that JuB treatment upregulated the levels of total Nrf2, facilitated its nuclear translocation, upregulated the expression of HO-1 and NQO-1, and inhibited the APAP-induced STING pathway activation. Finally, we verified that the beneficial effects of JuB were weakened by DMXAA and ML385. CONCLUSION: Our study suggested that JuB could ameliorate APAP-induced hepatic damage and verified a previously unrecognized mechanism by which JuB prevented APAP-induced hepatotoxicity through adjusting the Nrf2-STING pathway.

PABPN1 functions as a predictive biomarker in colorectal carcinoma.

PURPOSE: PABPN1 acts as a modulator of poly(A) tail length and alternative polyadenylation. This research was aimed to explore the role of PABPN1 in colorectal cancer (CRC). METHODS: Public databases were performed to analyze expression, location, roles of prognosis and tumor immunity and interaction with RNAs and proteins of PABPN1. To investigate PABPN1 expression in tissues, 78 CRC specimens were collected to conduct IHC, and 30 pairs of frozen CRC and corresponding adjacent normal tissues were used to conduct qRT-PCR and WB. In addition, in vitro experiments were then carried out to identify the role of PABPN1 in CRC. RESULTS: Compared with normal tissues, PABPN1 expression was significant higher in CRC. Its high level predicted poor outcome of CRC. Th1 and Treg had significant negative relationships not only with PABPN1 expression, but also with six molecules interacting with PABPN1, including IFT172, KIAA0895L, RECQL4, WDR6, PABPC1 and NCBP1. In addition, PABPN1 had negative relationships with quite a few immune markers, such as CSF1R, IL-10, CCL2 and so on. In cellular experiments, silencing PABPN1 inhibited proliferation and promoted apoptosis in HCT-116 CRC cells. CONCLUSION: In summary, PABPN1 might become a novel biomarker and correlate with tumor immunity in CRC.

Role of LncRNA MIR99AHG in breast cancer: Bioinformatic analysis and preliminary verification.

Objective: This research was aimed to preliminarily explore the clinical roles and potential molecular mechanisms of MIR99AHG and its significant transcripts in breast cancer (BRCA). Methods: Public databases were utilized to analyze the expression and prognostic roles of MIR99AHG and its transcripts. Relationships between MIR99AHG expression and immune cells infiltration were analyzed in Xiantao platform. In addition, co-expressed genes and interacting proteins of MIR99AHG were predicted. CancerSEA analyzed its relationship with functional states. Next, CNV status, DNA methylation, interacting transcription factors (TFs) and ceRNA network were analyzed to explore its possible mechanisms. Then, RNA ISH and FISH assays were used to detect its expression and location in BRCA tissues and cell lines, respectively. Finally, qRT-PCR was utilized to investigate MIR99AHG expression in cell lines. Results: Compared with the corresponding normal tissues, MIR99AHG expression levels were lower in all BRCA subtypes, and luminal B's was the lowest one. And MIR99AHG expression was negatively related to the tumor stage. In addition, 4 transcripts (ENST00000619222.4, ENST00000418813.6, ENST00000602901.5 and ENST00000453910.5) of MIR99AHG showed significant differences in the expression. Databases also suggested that the high MIR99AHG expression levels indicated good prognosis, especially in patients without lymph node metastasis. Xiantao found that MIR99AHG was positively related to 17 immune cells and negatively linked with 2 immune cells. CancerSEA analysis showed no relationships between MIR99AHG and functional states. From GEPIA and BCIP databases, 19 co-expressed genes were highly related to these four significant transcripts of MIR99AHG. StarBase, RNAct and HDOCK showed that several tumor-associated proteins, including U2AF65, hnRNPC, AEBP2, CHIC1 and so on, might interact with MIR99AHG. Genetically, BRCA had a higher proportion of MIR99AHG CNV loss than CNV gain, and the high level of DNA methylation indicated a good prognosis. Furthermore, 19 TFs were predicted to combine with the promoter of MIR99AHG. Then, we screened out 10 miRNAs potentially interacting with the significant transcripts of MIR99AHG, and five were significantly increased in breast tumors compared to normal tissues, including miR-194-5p, miR-320 b and so on, which could combine 14 mRNAs. Through ISH and FISH assays, we verified that MIR99AHG was down-regulated in BRCA samples and cell lines in comparison to non-tumor tissues and mammary epithelial cell line (MCF10A), and MIR99AHG was located both in cytoplasm and nucleus. qRT-PCR assay also showed the lower expression of MIR99AHG in breast cancer cells than that in MCF10A. Conclusion: These results indicate that MIR99AHG can be a favorable prognostic indicator for BRCA. ENST00000619222.4, ENST00000418813.6, ENST00000602901.5 and ENST00000453910.5 are significant transcripts and their down-regulation may play crucial roles in the progression of BRCA.

[Effects of soil meso- and micro-fauna on litter decomposition under nitrogen deposition and rainfall changes]. / 氮沉降与降雨变化下中小型土壤动物对凋落物分解的影响.

Soil fauna are important regulators of litter decomposition and nutrient transformation. Nitrogen deposition and rainfall changes driven by global changes could affect litter decomposition by changing environment and soil faunal community. Different mesh size (2 mm and 0.01 mm) litter bags were used to explore how soil meso- and micro-fauna contribute to decomposition of Stipa breviflora litter under nitrogen deposition and rainfall changes. The experiment followed split-plot design, with rainfall change (natural rainfall, CK; rainfall addition 30%, W; rainfall reduction 30%, R) as the main trement and nitrogen addition (0, N0; 30, N30; 50, N50; 100 kg·hm-2·a-1, N100) as the sub-treatment. The results showed that: 1) Rainfall change significantly affected litter decomposition rate, which was increased by rainfall addition. Moreover, litter decomposition rate was accelerated with increasing nitrogen addition rates. Litter residual rate decreased gradually with increasing N addition, and got to the highest in N100. Litter decomposition rate decreased first and then increased, and peaked in N50 in rain reduction and natural rainfall treatment. There was no significant interactions between rainfall change and nitrogen addition in affecting litter decomposition. 2) During the whole decomposition process, a total of 1577 soil meso- and micro-fauna were captured, belonged to 1 phyla, 3 classes, 13 orders (including suborders) and 49 families. The dominant groups were Acarina, Coleoptera larvae, and Collembola. Nitrogen addition significantly increased abundance and group numbers of soil meso- and micro-fauna. 3) The litter mass residue rate was significantly negatively correlated with abundance and group numbers of soil meso- and micro-fauna. The contribution rate of soil meso- and micro-fauna to litter decomposition increased with increasing rainfall. In summary, soil meso- and micro-fauna had a positive effect on decomposition of Stipa breviflora litter in desert steppe. Their contribution to litter was promoted by the enhancement of soil mesofauna abundance and group under rainfall and nitrogen addition. Excessive nitrogen would inhibit soil meso- and micro-fauna community and group density when water was insufficient, and would thus weaken the function of soil mesofauna to litter decomposition.

An Immune Risk Score Predicts Survival of Patients with Acute Myeloid Leukemia Receiving Chemotherapy.

PURPOSE: Prediction models for acute myeloid leukemia (AML) are useful, but have considerable inaccuracy and imprecision. No current model includes covariates related to immune cells in the AML microenvironment. Here, an immune risk score was explored to predict the survival of patients with AML. EXPERIMENTAL DESIGN: We evaluated the predictive accuracy of several in silico algorithms for immune composition in AML based on a reference of multi-parameter flow cytometry. CIBERSORTx was chosen to enumerate immune cells from public datasets and develop an immune risk score for survival in a training cohort using least absolute shrinkage and selection operator Cox regression model. RESULTS: Six flow cytometry-validated immune cell features were informative. The model had high predictive accuracy in the training and four external validation cohorts. Subjects in the training cohort with low scores had prolonged survival compared with subjects with high scores, with 5-year survival rates of 46% versus 19% (P < 0.001). Parallel survival rates in validation cohorts-1, -2, -3, and -4 were 46% versus 6% (P < 0.001), 44% versus 18% (P = 0.041), 44% versus 24% (P = 0.004), and 62% versus 32% (P < 0.001). Gene set enrichment analysis indicated significant enrichment of immune relation pathways in the low-score cohort. In multivariable analyses, high-risk score independently predicted shorter survival with HRs of 1.45 (P = 0.005), 2.12 (P = 0.004), 2.02 (P = 0.034), 1.66 (P = 0.019), and 1.59 (P = 0.001) in the training and validation cohorts, respectively. CONCLUSIONS: Our immune risk score complements current AML prediction models.

[Impact of salinity on nitrification in the process of biological nitrogen removal and its mechanism: a review].

Wastewater with high salinity is widely distributed, biological nitrogen removal process is inhibited by salt when it is used to treat wastewater containing high concentration of salt and ammonium. Nitrification is the key step of biological nitrogen removal process, thus researching the effect of salinity on nitrification is significant. In this article, the research progress of the impact of salinity on wastewater biological nitrification process was summarized. The influences of salinity stress on various aspects of nitrification process, including the efficiency of ammonia oxidation and nitrite oxidation processes, and the structure of aggregates, the characteristics of flocs and microbial community structure, were analyzed. The mechanism of nitrification process under high salinity was elaborated, providing a theoretical advice for designing biological nitrogen removal system of wastewater with high concentration of salt and ammonium.

Transumbilical single-incision endoscopic splenectomy: report of ten cases.

AIM: To investigate the feasibility and clinical application of transumbilical single-incision endoscopic splenectomy using conventional laparoscopic instruments. METHODS: Between 2010 and 2012, transumbilical single-incision endoscopic splenectomy was performed in 10 patients in our department, of whom 4 had refractory idiopathic thrombocytopenic purpura, 4 had enlarged splenic cyst and 2 had splenic hematoma. A 2.5-cm curved incision was made at the lower umbilicus edge, and a 10 mm laparoscope was inserted into the middle of the incision. A 5-mm harmonic scalpel was placed on the right side, and a 5-mm auxiliary instrument on the left side of the laparoscope. Splenic ligaments were incised with a harmonic scalpel, and the splenic pedicle was cut with an Endo-gastrointestinal anastomosis. The spleen was dissected and placed in a large retrieval bag, blended, and then removed. RESULTS: All transumbilical single-incision endoscopic splenectomies were performed successfully with mean operative time of 80 ± 5 min and mean blood loss of 150 ± 20 mL. Conversion to laparotomy or multi-port laparoscopic surgery was not required in all cases. All patients were discharged on postoperative days 4-6. During the postoperative hospitalization period, no painkillers were required. No intra-abdominal complications such as infection, ascites, gastric leakage, pancreatic leakage, or wound infection occurred in any case during the 6-mo follow-up. CONCLUSION: Transumbilical single-incision endoscopic splenectomy using conventional laparoscopic instruments is technically feasible and safe in selected patients.

[Research advances in identifying nitrate pollution sources of water environment by using nitrogen and oxygen stable isotopes].

Water body' s nitrate pollution has become a common and severe environmental problem. In order to ensure human health and water environment benign evolution, it is of great importance to effectively identify the nitrate pollution sources of water body. Because of the discrepant composition of nitrogen and oxygen stable isotopes in different sources of nitrate in water body, nitrogen and oxygen stable isotopes can be used to identify the nitrate pollution sources of water environment. This paper introduced the fractionation factors of nitrogen and oxygen stable isotopes in the main processes of nitrogen cycling and the composition of these stable isotopes in main nitrate sources, compared the advantages and disadvantages of five pre-treatment methods for analyzing the nitrogen and oxygen isotopes in nitrate, and summarized the research advances in this aspect into three stages, i. e. , using nitrogen stable isotope alone, using nitrogen and oxygen stable isotopes simultaneously, and combining with mathematical models. The future research directions regarding the nitrate pollution sources identification of water environment were also discussed.

Learning curve of transumbilical suture-suspension single-incision laparoscopic cholecystectomy.

AIM: To investigate the learning curve of transumbilical suture-suspension single-incision laparoscopic cholecystectomy (SILC). METHODS: The clinical data of 180 consecutive transumbilical suture-suspension SILCs performed by a team in our department during the period from August 2009 to March 2011 were retrospectively analyzed. Patients were divided into nine groups according to operation dates, and each group included 20 patients operated on consecutively in each time period. The surgical outcome was assessed by comparing operation time, blood loss during operation, and complications between groups in order to evaluate the improvement in technique. RESULTS: A total of 180 SILCs were successfully performed by five doctors. The average operation time was 53.58 ± 30.08 min (range: 20.00-160.00 min) and average blood loss was 12.70 ± 11.60 mL (range: 0.00-100.00 mL). None of the patients were converted to laparotomy or multi-port laparoscopic cholecystectomy. There were no major complications such as hemorrhage or biliary system injury during surgery. Eight postoperative complications occurred mainly in the first three groups (n = 6), and included ecchymosis around the umbilical incision (n = 7) which resolved without special treatment, and one case of delayed bile leakage in group 8, which was treated by ultrasound-guided puncture and drainage. There were no differences in intraoperative blood loss, postoperative complications and length of postoperative hospital stay among the groups. Bonferroni's test showed that the operation time in group 1 was significantly longer than that in the other groups (F = 7.257, P = 0.000). The majority of patients in each group were discharged within 2 d, with an average postoperative hospital stay of 1.9 ± 1.2 d. CONCLUSION: Following scientific principles and standard procedures, a team experienced in multi-port laparoscopic cholecystectomy can master the technique of SILC after 20 cases.

[Methods for the assessment of organic compounds biodegradability: A review].

There are plenty of methods used for the assessment of organic compounds biodegradability, but lack of comprehensive literatures in systematically introducing the assessment methods and guiding the choice of the methods. This paper briefly introduced the indicative parameters in assessing organic compounds biodegradability and the assessment methods of aerobic and anaerobic biodegradation, with the focus on the principles and criteria in the choice of the assessment methods, and analyzed in detail the reasons for the differences in the biodegradation rates of organic compounds when different test methods were adopted. Taking the standards established by the Organization for Economic Co-operation and Development (OECD) as an example, the process of choosing and applying the assessment methods was introduced, the systematic method-choosing route was integrated, and the advantages of the OECD standard methods were pointed out.

[Watershed water environment pollution models and their applications: a review].

Watershed water environment pollution model is the important tool for studying watershed environmental problems. Through the quantitative description of the complicated pollution processes of whole watershed system and its parts, the model can identify the main sources and migration pathways of pollutants, estimate the pollutant loadings, and evaluate their impacts on water environment, providing a basis for watershed planning and management. This paper reviewed the watershed water environment models widely applied at home and abroad, with the focuses on the models of pollutants loading (GWLF and PLOAD), water quality of received water bodies (QUAL2E and WASP), and the watershed models integrated pollutant loadings and water quality (HSPF, SWAT, AGNPS, AnnAGNPS, and SWMM), and introduced the structures, principles, and main characteristics as well as the limitations in practical applications of these models. The other models of water quality (CE-QUAL-W2, EFDC, and AQUATOX) and watershed models (GLEAMS and MIKE SHE) were also briefly introduced. Through the case analysis on the applications of single model and integrated models, the development trend and application prospect of the watershed water environment pollution models were discussed.

[Thermophiles and their working mechanisms in degrading excess sludge: a review].

Activated sludge process is widely used in treating a wide variety of wastewater, but the by-product is the large amount of excess sludge. To treat the excess sludge properly could spend 25%-60% of the total cost of wastewater treatment, while improperly treating the sludge could cause serious secondary pollution. Therefore, the reduction of excess sludge is becoming a rising challenge. Using thermophiles to degrade excess sludge is a way easy in operation and inexpensive in maintenance, being a promising method in application. This paper reviewed the recent progress in the researches of sludge-degrading thermophiles, their working mechanisms, and the enzymes from thermophiles, such as thermophilic proteolytic enzymes and thermophilic lipases which play an important role in the degradation of sludge. The factors affecting the degradation of sludge by thermophiles were summarized, and the perspectives for the further research on the application of thermophiles in digesting sludge were discussed.

[Bio-treatment of grease wastewater: research progress].

In conventional wastewater bio-treatment, little attention has been paid on the bio-degradation of grease, causing low efficiency in the process, and thereby, further study should be made on the development and application of related mature and effective bio-treatment techniques. This paper summarized the pathways and mechanisms of grease bio-degradation in wastewater treatment, with the focus on the research progress in the functional microbes involved in lipid hydrolysis and long-chain fatty acid degradation, and briefly introduced a series of new treatment technologies based on the habitat differences of the functional microbes. The key breakthrough directions in the technological study of grease bio-degradation were prospected, expecting to provide theoretical guidance to the development of the related technologies.

[Observation of the grafting of platelet-derived growth factor gene-modified artificial composite skin on rat wounds].

OBJECTIVE: To observe the effects of the grafting of a platelet-derived growth factor gene-modified artificial composite skin on rat wounds with full thickness defect. METHODS: Platelet derived growth factor-B (PDGF-B) eukaryotic expression plasmid was constructed, and the fibroblasts were transfected with it by liposome mediation. Artificial composite skins 1 and 2 were constructed respectively. The skin1 was composed of keratinocyte, porcine acellular dermal matrix and PDGF-B gene-transfected fibroblasts while the skin 2 contained keratinocyte, porcine acellular dermal matrix and fibroblasts. The two kinds of composite skin were grafted onto wounds on the rat back to form composite skin group 1 (C1) and 2 (C2), respectively, with 18 rats in each group. Eight rats with wounds without treatment served as control (C) group. The survival rate of the composite skin was observed at 2 post-operative weeks (POWs). The rat wounds were examined grossly on 2, 4 and 6 POWs for the calculation of wound contraction rate. Wound tissue samples were harvested for histological examination. RESULTS: (1) Up to 2 POWs, 14 grafts in C1 group survived completely, 3 with partial survival and 1 failure. In C2 group, 10 skin grafts survived completely, 4 with partial survival and 4 failures. (2) A scab was formed in the wound at 2 POW in C group. The surface of the grafted skin in C1 group was smooth, elastic, and showed good anti-friction properly, and it was better in quality compared with that in other two groups at 6 POW. (3) The wound contraction rate of the grafts in C group of rats was higher than that in C1 and C2 groups at 2, 4 and 6 POWs, while that in C1 was lower than that in C2 group. (4) Capillary formation was more intense in the grafted skins in C1 group at 2 POWs, and the epithelia differentiated well into 7 to 10 layers of epithelial cells with compact and orderly arrangement and evenly distributed fibrous tissue at 6 POWs. CONCLUSION: Repair of the wound with artificial composite skin containing PDGF-B gene could improve the quality of wound healing.

[Effect of glucocorticoid with traditional Chinese medicine in severe acute aespiratory syndrome (SARS)].

OBJECTIVE: To evaluate the effects of traditional Chinese medicine in 461 cases of severe acute respiratory syndrome(SARS) on glucocorticoid's dosage. METHOD: By using the polycentric nonrandomized concurrent controled trial and under the condition of glucocorticoid use, the patierts were divided into two groups: the integrated traditional Chinese and western mendicine(ITCWM) and simplicity western mendicine alone(WM). The observation indexes were time in hospital, pneumonia duration, mortality, glucocorticoid's gross dosage, glucocorticoid's average dosage of days and glucocorticoid use time. RESULT: In the ITCWM group, average time in hospital was shortened (P = 0.058), pneumonia duration was shortened (P = 0.057), mortality fell (P = -0.001). The median of glucocorticoid' s gross dosage was 1,277.0 mg x d(-1) in the ITCWM group, and that was 1,680.0 mg x d(-1) in the WM group (P = 0.083). The median of glucocorticoid's average dosage of days was 84.40 mg x d(-1) in the ITCWM group, and that was 115.33 mg x d(-1) in the WM group (P = 0.025). According to the analysis of 461 cases divided by stages and different ponderance, within 7 days after illness, in the ITCWM group, the glucocorticoid' s average dosage decreased. In the common type, the dosage in the ITCWM and in the WM was 146.43 mg x d(-1), and 183.64 mg x d(-1), respectively (P = 0.057), in the severe type, that was 137.71 and 177.86 mg x d(-1), respectively (P = 0.001). CONCLUSION: Compared with the group of simplicity western mendicine, in the group of integratived Chinese and western mendicine, time in hospital shorten, pneumonia duration shorten, mortality fall, simultaneity, glucocorticoid's average dosage is decreased. The use of TCM in the forepart of treatment can be capable of decreasing glucocorticoid's dosage.

[Preparation of porcine acellular dermal matrix by low concentration of trypsin digestion and repeated freeze-thaw cycles].

OBJECTIVE: To establish a new method for the preparation of porcine acellular dermal matrix. METHODS: The antigenicity of the porcine dermis was weakened by removing epidermal and dermal cells from the porcine skin through the digestion with low-concentration trypsin and repeated freeze-thaw cycles. Split thickness porcine skin was treated with 0.05% trypsin to remove the cells from the epidermis and dermis. Repeated freeze-thaw cycles were employed to further weed out the residual cells within the dermis. The prepared acellular dermis was then examined grossly, as well as histologically, and also by immunohistochemical method. RESULTS: No cell could be identified in the prepared porcine acellular dermal matrix. The integral basement membrane was preserved on the surface of dermal matrix with compact dermal matrix collagen structure. CONCLUSION: Low concentration trypsinization and repeated freeze-thaw cycles seemed to be a simple and effective method for the preparation of xenogeneic acellular dermal matrix.

[Effect of expression of platelet-derived growth factor B gene on blood vessel reconstruction after tissue engineering skin grafting].

OBJECTIVE: To study the effect of PDGF on dermal blood vessel reconstruction by transplanted tissue-engineering skin containing PDGF-B gene to rats. METHODS: The recombined eukaryotic expression vector, pcDNA3.1-hPDGF-B, was constructed and transfected into fibroblasts mediated by LipofectAMINE. Keratinocytes + acellular dermal matrix (group A), keratinocytes + acellular dermal matrix + fibroblasts (group B), keratinocytes + acellular dermal matrix + fibroblasts with PDGF gene (group C) were recombined respectively, then transplanted them to rat dorsum and evaluated the reconstruction of blood vessels in the dermis after 2, 4, 6 week postoperation. RESULTS: In 2-4 weeks after skin grafting the vascularization rate in group C was higher than that of group B and group A. The vascularization rates in all groups had no significant differences in six weeks (P > 0.05). CONCLUSION: PDGF-B gene plays an important role in reconstruction of blood vessels in the dermis at early tissue-engineering skin grafting, which ensures the take of grafted tissue-engineering skin.