Structural identification and combination mechanism of iron (II)-chelating Atlantic salmon (Salmo salar L.) skin active peptides.

In order to utilize salmon skin for high value, and investigate the structural identification and combination mechanism of iron (II)-chelating peptides systemically, Atlantic salmon (Salmo salar L.) skin, a by-product of Atlantic salmon processing, was treated by two-step enzymatic hydrolysis to obtain salmon skin active peptides (SSAP). Then they reacted with iron (II) to obtain iron (II)-chelating salmon skin active peptides (SSAP-Fe) with a high iron (II) chelating ability of 98.84%. The results of Fourier transform infrared spectroscopy (FTIR), circular dichroism (CD) spectroscopy, 8-anilino-1-naphthalenesulfonic acid ammonium salt hydrate (ANS) combined fluorescence measurement, isothermal titration calorimetry (ITC) and full wavelength ultraviolet (UV) scanning showed that the structural characteristics of SSAP changed before and after chelating iron (II). Reverse phase high performance liquid chromatography (RP-HPLC) and mass spectrometry were used to identify and quantify the peptides in SSAP-Fe. Four peptide sequences (STEGGG, GIIKYGDDFMH, PGQPGIGYDGPAGPPGPPGPPGAP and QNQRESWTTCRSQSSLPDG) were identified. The content of PGQPGIGYDGPAGPPGPPGPPGAP was the highest, at 25.17 µg/mg. The pharmacokinetic and pharmacodynamic properties of these four peptides were also investigated, and the results indicated that they have satisfactory predicted ADMET properties. Molecular docking technology was used to analyze the binding sites between iron (II) and SSAP, and it was found that PGQPGIGYDGPAGPPGPPGPPGAP had the lowest predicted binding energy with iron (II) and the most stable predicted binding energy with iron (II). This results showed that the stability of SSAP-Fe were closely related to the number of covalent bonds and the types of amino acids. This study revealed the structure and combination mechanism of SSAP-Fe, and indicated that SSAP-Fe prepared by chelation may be used as a Fe supplement that can be applied in functional foods or ingredients.

Effect of the preoperative prognostic nutritional index on the long-term prognosis in patients with borderline resectable pancreatic cancer after pancreaticoduodenectomy.

Background: The preoperative prognostic nutritional index (PNI) is an indicator of systemic immune-nutritional condition and is a well-known prognostic biomarker in cancer patients. This study aims to reflect the correlation between the preoperative PNI and prognosis in patients with borderline resectable pancreatic cancer (BRPC) after pancreaticoduodenectomy (PD). Methods: Medical records of patients with BRPC after PD between Jan 2011 and Dec 2021 in our hospital were retrospectively analyzed. The preoperative PNI was calculated, and the receiver operating characteristic curve was obtained based on the preoperative PNI and the 1-year survival rate. Patients were divided into two groups (High-PNI and Low-PNI) following the best cut-off value of the preoperative PNI, and demographic and pathologic findings were compared between the two groups. Univariate and multivariate analysis were performed to identify risk factors in recurrence and long-term survival. Results: The best cut-off value for the preoperative PNI was 44.6 (sensitivity: 62.46%; specificity: 83.33%; area under the curve: 0.724). Patients in the low-PNI group had significantly shorter recurrence-free survival (P=0.008) and overall survival (P=0.009). The preoperative PNI (P=0.009) and lymph node metastasis (P=0.04) were independent risk factors for tumor recurrence. The preoperative PNI (P=0.001), lymph node metastasis (P=0.04), neoadjuvant chemotherapy (P=0.04) were independent risk factors for long-term survival in patients. Conclusion: The preoperative PNI, lymph node metastasis, neoadjuvant chemotherapy were independent risk factors for recurrence and long-term survival in patients with BRPC. The preoperative PNI might be an indicator that can predict BRPC patients' recurrence and survival. Patients with high-PNI would benefit from neoadjuvant chemotherapy.

Browsing makes you feel less bad: An ecological momentary assessment of passive Qzone use and young women's negative emotions.

Passively browsing other's content on social networking sites (SNS) is popular among young females. It remains unclear how passive use relates to female's negative emotions, and especially whether short-term associations are confined by individual differences. This study used ecological momentary assessment over the course of one week to examine the associations between passive use of SNS and negative emotions, and investigated whether individual differences (i.e., self-esteem and life satisfaction) would moderate this relationship. A sample of N = 99 Chinese female undergraduates (Mage = 18.81, SDage = 0.84) completed a baseline online survey on self-esteem and life satisfaction, and received a daily online survey about their Qzone use as well as their negative emotions for seven days. Multilevel modeling revealed that passively browsing Qzone on a given day was associated with less negative emotions. However, the within-person association was independent of self-esteem and life satisfaction. Implications of passive SNS use are discussed especially regarding their potential to reduce negative feelings among Chinese young female undergraduate students, at least in the short term.

Plasmacytoid dendritic cells mediate the tolerogenic effect of CD8+regulatory T cells in a rat tolerant liver transplantation model.

BACKGROUND: Tolerance is more easily induced in liver transplant models than in other organs; CD8+CD45RClowregulatory T cells (Tregs) have been shown to induce tolerance in heart allografts. Whether CD8+CD45RClowTregs could induce tolerance in a liver transplant model and how dendritic cells (DCs) mediate the CD8+CD45RClowTregs effect remains to be investigated. METHODS: A rat liver transplantation model was established and used to test tolerance and acute rejection compared to control groups. Liver function and histopathological changes of allograft were examined by enzyme-linked immunosorbent assay (ELISA) and haematoxylin and eosin (H&E) staining, respectively. The distribution and proportion of CD8+CD45RClowTregs and plasmacytoid dendritic cells (pDCs) in the allografts and spleen were determined using flow cytometry. Cytokine secretion levels were determined using ELISA and real-time quantitative PCR (qRT-PCR). RESULTS: The rat liver transplantation model was well established, with a success rate of 93.3% (28/30). The mean survival time of the tolerant and acute-rejection rats were 156 and 14 days, respectively. The proportions of CD8+CD45RClowTegs were higher in the allografts of tolerant rats than in those of acute-rejection rats (33.1 ± 4.3 and 12.4 ± 4.6, respectively; P = 0.04). Significant accumulation of pDCs was observed in tolerant liver graft rats compared to that in acute-rejection rats (1.46 ± 0.23 and 0.80 ± 0.20, respectively; P = 0.02). Importantly, CD8+CD45RClowTregs were positively associated with the frequency of pDCs (P = 0.001, r2 = 0.775). The protein and mRNA expression of IL-10 and TGF-ß in the allograft group were increased, possibly being responsible for tolerance induction. CONCLUSION: CD8+CD45RClowT cells interact with pDCs through the induction of IL-10 and TGF-ß expression and are responsible for inducing immune tolerance in rat liver transplantation.

Prognostic Value of Preoperative NLR and Vascular Reconstructive Technology in Patients With Pancreatic Cancer of Portal System Invasion: A Real World Study.

The purpose was aimed to establish a simple computational model to predict tumor prognosis by combining neutrophil to lymphocyte Ratio (NLR) and biomarkers of oncological characteristics in patients undergoing vascular reconstructive radical resection of PDAC. The enrolled patients was divided into high or low NLR group with the cutoff value determined by the receiver operator characteristic (ROC) curve. Different vascular anastomoses were selected according to the Chaoyang classification of PDAC. Survival rates were calculated using the Kaplan-Meier and evaluated with the log-rank test. Cox risk regression model was used to analyze the independent risk factors for prognostic survival. The optimal cut-off value of NRL was correlated with the differentiation, tumor size, TNM stage and distant metastasis of advanced PDAC. A curative resection with vascular reconstructive of advanced PDAC according to Chaoyang classification can obviously improve the survival benefits. Cox proportional hazards demonstrated higher evaluated NLR, incisal margin R1 and lymphatic metastasis were the independent risk predictor for prognosis with the HR > 2, meanwhile, age beyond 55, TNM stage of III-IV or Tumor size > 4cm were also the obvious independent risk predictor for prognosis with the HR ≤ 2. The advanced PADC patients marked of RS group (3 < RS ≤ 6) showed no more than 24 months of survival time according to RS model based on the six independent risk predictors. Vascular reconstruction in radical resection of advanced PDAC improved survival, higher elevated NLR (>2.90) was a negative predictor of DFS and OS in those patients accompanying portal system invasion.

Rapamycin treated tol-dendritic cells derived from BM-MSCs reversed graft rejection in a rat liver transplantation model by inducing CD8+CD45RC-Treg.

OBJECTIVE: To investigate the influence of tolerance dendritic cells (tolDCs), generated from Bone marrow mesenchymal stem cells (BM-MSCs) treated with rapamycin (Rapa) on liver allograft survival in a rat acute liver transplantation model. METHODS: Different GM-CSF induction project was used to obtain immature DCs (imDCs), mature DCs (matDCs) or tolDCs from BM-MSCs. First, MLR was performed to analyze the activity of tolDCs on polyclonaly stimulated total T cells. Then, co-cultured imDCs, matDCs and tolDCs with CD8+T cells isolated by magnetic activated cell sorting to analyze the influence on its regulatory characteristic. Last, the established rat acute liver transplantation model were adoptive transfused with imDCs, matDCs or tolDCs isolated by anti-CD11c immunomagnetic beads. The phenotype of DC cells and level of CD8+Treg in the culture system and in vivo, the expression of CD8 and CD45RC in the tissues were analyzed by flow cytometry and immunohistochemistry, respectively. RESULTS: The loGM-CSF plus IL-4 decreased the costimulatory molecules of CD80/86 and MHC class II of DCs comparison with hiGM-CSF from BM-MSCs no matter whether stimulation by LPS (P<0.05). Rapa treated not only reduced the expression of CD80/86 and MHC class II but also down-regulated the expression of CD11c after LPS stimulation which was more obviously in tolDCs by loGM-CSF project (P<0.05). Moreover, tolDCs displayed a rather higher level of IL-10 and low level of IL-12p70 than others (P<0.01), which shown a rather lower stimulative effect on the proliferation of T cells comparison with matDCs and imDCs. Co-cultured with CD8+Treg showed an improvement on induction of CD8+TCR+CD45RC-T cells (CD8+Treg) in ex vivo. The rats transfused with tolDCs has a delayed survival benefits with high level of CD8+Tregs (P<0.01) and high expression of CD45RC in liver tissue (P<0.01) and spleen when comparison with other groups. The infused tolDCs improved a mean survival time (MST) of 32 days comparison with a MTS of 9.5 days and 15.75 days displayed by rat that per-infused with matDCs and imDCs, respectively. CONCLUSION: Rapa modified tolDCs derived from BM-MSCs reversed graft rejection by improve tolerance characteristics of CD8+CD45RC-Treg in acute liver rat transplantation.

In-hospital mortality of liver transplantation and risk factors: a single-center experience.

BACKGROUND: Liver transplantation (LT) is a life-saving treatment for patients with end-stage liver disease and acute liver failure. However, in-hospital death cannot be avoided. We designed this study to analyze patients' in-hospital mortality rate after LT and the factors correlated with in-hospital death. METHODS: The data of patients who received LT in our hospital between January 11, 2015, and November 19, 2019, were obtained from the China Liver Transplant Registry and medical records. The in-hospital mortality rate was calculated, and factors related to mortality, cause of death, and factors related to cause of death were analyzed by reviewing patients' data. RESULTS: A total of 529 patients who underwent cadaveric LT were enrolled in this study. Modified piggyback orthotopic LT was performed for all patients. Seventy patients died in the hospital after LT, and the in-hospital mortality rate was 13.2%. Factors including model for end-stage liver disease (MELD) score, Child-Pugh grading, intraoperative blood loss, and anhepatic phase were correlated with in-hospital death. MELD score and intraoperative blood loss were determined as the two independent risk factors of in-hospital death. The first two causes of death were infection (34.3%) and primary non-function (15.7%). Pulmonary fungal infection was the main cause of infectious death. MELD score was the independent risk factor for infectious death, and both body mass index of donors and cold ischemic time were independent risk factors of primary non-function. CONCLUSIONS: In-hospital death poses a threat to certain patients undergoing LT. Our study suggests that the main cause of in-hospital death is an infection, followed by primary non-function.

Reduction of FoxP3+ Tregs by an immunosuppressive protocol of rapamycin plus Thymalfasin and Huaier extract predicts positive survival benefits in a rat model of hepatocellular carcinoma.

BACKGROUND: Investigate immunoregulation and anti-tumor immunity of FoxP3+Tregs after treatment with rapamycin (RAPA/SRL) plus thymalfasin (Zadaxin) and Huaier extract (PS-T) in a hepatocellular carcinoma (HCC) rat model simulating HCC relapse after liver transplant (LT). METHODS: We successfully established a rat model simulating HCC relapse after LT using an optimized chemical induction method with TACROLIMUS, methylprednisolone, and diethylnitrosamine as identified by visible liver nodules and hematoxylin-eosin staining. The model rats were then treated with RAPA, Zadaxin, and PS-T. Immune status changes were analyzed by flow cytometry, and protein expression of Akt and mTOR was determined by western blotting. Cytokines were measured by ELISAs. RESULTS: Combined therapy by RAPA plus Zadaxin and PS-T obviously alleviated hepatic pathological changes and significantly decreased the levels of FoxP3+Tregs in peripheral blood, the spleen, and the liver (P<0.05) and expression of mTOR protein (P<0.01) in the liver, obviously improved survival time (P=0.02). Moreover, the levels of CD8+T cells were increased significantly to almost normal levels (P<0.05) in comparison with no SRL monotherapy protocols. Inhibitory cytokines were also decreased in accordance with FoxP3+Tregs. Significant decreases of IL-10 and TGF-ß were observed after SRL-based therapy (P<0.01) in comparison with the other groups. Serum alpha fetoprotein (AFP) and vascular endothelial growth factor (VEGF) levels were also decreased significantly (P<0.05). FoxP3+Tregs showed a negative correlation with CD8+ and CD4+/CD8+T cells and a positive correlation with AFP, and VEGF (P<0.05). CONCLUSIONS: SRL-based therapy reduces FoxP3+Tregs to decrease secreted inhibitory cytokines which may enhancement the viability and number of CD8+T cells to exert anti-tumor effects that are mainly mediated through the AKT-mTOR signaling pathway.

Breviscapine ameliorates CCl4­induced liver injury in mice through inhibiting inflammatory apoptotic response and ROS generation.

Acute liver injury is characterized by fibrosis, inflammation and apoptosis, leading to liver failure, cirrhosis or cancer and affecting the clinical outcome in the long term. However, no effective therapeutic strategy is currently available. Breviscapine, a mixture of flavonoid glycosides, has been reported to have multiple biological functions. The present study aimed to investigate the effects of breviscapine on acute liver injury induced by CCl4 in mice. C57BL/6 mice were subjected to intraperitoneal injection with CCl4 for 8 weeks with or without breviscapine (15 or 30 mg/kg). Mice treated with CCl4 developed acute liver injury, as evidenced by histological analysis, Masson trichrome and Sirius Red staining, accompanied with elevated levels of alanine aminotransferase and aspartate aminotransferase. Furthermore, increases in pro­inflammatory cytokines, chemokines and apoptotic factors, including caspase­3 and poly(ADP ribose) polymerase­2 (PARP­2), were observed. Breviscapine treatment significantly and dose­dependently reduced collagen deposition and the fibrotic area. Inflammatory cytokines were downregulated by breviscapine through inactivating Toll­like receptor 4/nuclear factor-κB signaling pathways. In addition, co­administration of breviscapine with CCl4 decreased the apoptotic response by enhancing B­cell lymphoma-2 (Bcl­2) levels, while reducing Bcl­2­associated X protein, apoptotic protease activating factor 1, caspase­3 and PARP activity. Furthermore, CCl4­induced oxidative stress was blocked by breviscapine through improving anti­oxidants and impeding mitogen­activated protein kinase pathways. The present study highlighted that breviscapine exhibited liver­protective effects against acute hepatic injury induced by CCl4 via suppressing inflammation and apoptosis.

Analysis of prognostic factors for pancreatic head cancer according to para-aortic lymph node.

This study was designed to investigate the relationship between prognosis of pancreatic head cancer and status of para-aortic lymph node (PALN). A total of 233 patients with pancreatic head cancer who underwent surgical resection between February 2008 and October 2015 were enrolled in this study. Univariate and multivariate analyses were used to reveal the prognostic factors. Prognostic factors for patients with and without metastasis of PALN were analyzed, respectively. The 5-year overall survival (OS) rate was 19.0% for all patients, and the positive rate of PALN metastasis was 18.9% (44/233). The 1-, 2-, 3-, and 5-year OS rates in patients without metastasis of PALN were 79.4%, 54.8%, 36.4%, and 22.9%, respectively, whereas the 1-, 2-, and 3-year survival rates were 54.0%, 14.8%, and 0%, respectively, in patients with metastasis of PALN. Preoperative CA19-9 level, tumor size, T status, N status, and adjuvant therapy were independent prognostic factors for all patients confirmed by multivariate analysis. For patients without PALN metastasis, back pain, tumor size, T status, N status, portal or superior mesenteric vein invasion, and adjuvant therapy were independent prognostic factors, while the only one influence factor for 2-year OS was adjuvant therapy for patients with metastasis of PALN. Metastasis of PALN was associated with poor prognosis for patients with pancreatic head cancer. Patients with and without metastasis of PALN had different prognostic factors, and adjuvant therapy was the only prognostic factor for patients with metastasis of PALN.

Resection of portal and/or superior mesenteric vein and reconstruction by using allogeneic vein for pT3 pancreatic cancer.

BACKGROUND AND AIM: There is still controversy on the outcomes of portal vein (PV) and/or superior mesenteric vein (SMV) resection in pancreatic cancer, and there are few reports about pancreaticoduodenectomy (PD) with PV/SMV resection and reconstruction by using allogeneic vein. This study is to explore the outcomes of PD with PV/SMV resection and reconstruction by using allogeneic vein for pT3 pancreatic cancer with venous invasion. METHODS: Clinicopathological data of patients underwent PD with en bloc resection of PV/SMV and reconstruction by using internal iliac from August 20, 2013 to July 25, 2015 were collected and the data of patients with pT3 stage pancreatic head cancer with PV/SMV invasion were analyzed. The short- and long-term outcomes were presented. RESULTS: Thirty patients met the criteria of this study. PV resection and reconstruction were performed for 12 patients, SMV for 9 patients, and PV + SMV for 9 patients, respectively. The median operation time was 460 min, and the median intraoperative blood loss was 450 mL. R0 resection rate was 93.3%, total incidence of complications was 23.3%, and incidence of pancreatic fistula was 10%. The 1-year and 2-year overall survival rates were 68.6% and 39.2%, 1-year and 2-year disease free survival rates were 44.8% and 17.1%. CONCLUSIONS: PD with en bloc resection of PV/SMV and reconstruction by using allogeneic vein was safe and feasible for patients with pT3 stage pancreatic head cancer with PV/SMV invasion. A large-scale research with longer follow-up time is required to draw a significant conclusion.

[Effect of NaHCO3 stress on uptake and transportation of Na+, K+ and Ca2+ in three shrub species].

We detected absorption and transportation of ions in the leaves of Atriplex nummularia, Atriplex canescens and Lycium barbarum under NaHCO3 stress (300 mmol x L(-1)) by using atomic absorption spectrophotometry and non-invasive ion flux measurement. The results showed that leaves of the A. nummularia, A. canescens and L. barbarum exhibited a high capacity to induce the Na+ accumulation when compared with that of control. The higher the concentration of NaHCO3 treatment, the more Na+ accumulated in the leaves of the three plants under experimental condition. L. barbarum showed a higher Na+ efflux in the mesophyll cells, whereas A. nummularia and A. canescens showed a relative lower efflux. A lower K+ content and a higher Na+/K+ ratio were detected in leaves of A. nummularia and L. barbarum. However, a higher K+ content and a lower Na+/K+ ratio were seen in leaves of A. canescens. Due to induction of Ca2+ efflux under the NaHCO3 treatment, a lower Ca2+ content and a higher Na+/Ca2+ ratio were observed in L. barbarum. On the contrary, a higher Ca2+ influx was observed in A. nummularia and A. canescens. These results suggested that the three shrubs species had different Na+ segmentation strategies. The accumulation of Na+ inhibited Ca2+ absorption in leaves of L. barbarum, while in the A. nummularia and A. canescens, Ca2+ influx induced [Ca2+]cyt which preserved a less-depolarized PM and then inhibited K efflux. The maintaining of cellular K+/Na+ homeostasis in A. nummularia and A. canescens might be achieved by the induction of [Ca2+]cyt under the NaHCO3 treatment.

[Effect of compound Biejia Ruangan tablet on expressions of connective tissue growth factor mRNA and protein in kidney tissue of rats with adriamycin-induced nephropathy].

OBJECTIVE: To investigate the changes of connective tissue growth factor (CTGF) protein and CTGF mRNA in kidney tissue of rats with adriamycin (ADR)-induced nephropathy and to study the effects of compound Biejia Ruangan tablet (CBJRGT), a traditional Chinese herbal medicine for treatment of liver fibrosis. METHODS: A rat model of ADR-induced nephropathy after one-sided nephrectomy was established. Forty-five Wistar rats were randomly divided into 5 groups: normal control group, sham-operated group, untreated group, lotensin-treated group and CBJRGT-treated group. Pathological changes of the kidney tissue were observed by microscopy after 10-week drug administration. The expressions of CTGF protein and CTGF mRNA in the kidney tissue were measured by the methods of immunohistochemistry and in situ hybridization. RESULTS: The expressions of CTGF protein and CTGF mRNA in the normal and sham-operated groups were decreased in the intracytoplasm of glomerular mesangial cells, renal tubular epithelial cells and interstitial cells. Compared with the sham-operated group, the expressions of CTGF protein and CTGF mRNA in the untreated group were markedly increased and the development of renal fibrosis in the untreated group could be observed. CBJRGT could significantly decrease the expressions of CTGF protein and CTGF mRNA, and there was no significant difference between CBJRGT-treated group and lotensin-treated group. CONCLUSION: CBJRGT may suppress the development of fibrosis through down-regulating the expressions of CTGF protein and CTGF mRNA.

[Effects of Haikun Shenxi on expression of platelet-derived growth factor-B and mRNA in renal tissue of rats with adriamycin nephropathy].

OBJECTIVE: To investigate the effects of Haikun Shenxi on the expression of platelet-derived growth factor-BB (PDGF-BB) and mRNA in renal tissue of rats with adriamycin nephropathy. METHOD: Rat model was established by unilateral nephrectomy and injecting adriamycin intraperitoneally. The adriamycin-induced nephrotic rats were randomly divided into 6 groups: normal group, sham operation group, model group, lotensin treatment group, Haikun Shenxi low and high dose treatment groups (0.77, 0.08 mg x kg(-1). Ten weeks later, the 24 hour urine protein and blood biochemistry examinations and renal pathologic changes were observed, and the expression of PDGF-BB and mRNA was measured using immunohistochemical method. RESULT: Compared with model group, proteinuria and the levels of serum creatinine (Scr) , urea nitrogen (BUN) were decreased obviously in both Haikun Shenxi low and high dose groups. The expression of PDGF-BB and mRNA was mostly presented in cytoplasm of renal tubular epithelial cells and mesangial area, and it could be reduced significantly after treatment (P < 0. 05). CONCLUSION: The level of PDGF-BB and mRNA is high in renal tissue of adriamycin-induced nephrotic rats. This progress could be effectively inhibited by Haikun Shenxi and the mechanism may be that it can control the excessive expression of PDGF-BB and mRNA.