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Objective: This study explored the molecular mechanisms by which dexmedetomidine (Dex) alleviates cisplatin (CP)-induced acute kidney injury (AKI) in rats., Methods: CP-induced AKI models were established, and Dex was intraperitoneally injected at different concentrations into rats in the model groups. Subsequently, rats were assigned to the control, CP, CP + Dex 10 μg/kg, and CP + Dex 25 μg/kg groups. After weighing the kidneys of the rats, the kidney arterial resistive index was calculated, and CP-induced AKI was evaluated. In addition, four serum biochemical indices were measured: histopathological damage in rat kidneys was detected; levels of inflammatory factors, interleukin (IL)-1β, IL-18, IL-6, and tumor necrosis factor alpha, in kidney tissue homogenate of rats were assessed through enzyme-linked immunosorbent assay (ELISA); and levels of NLRP-3, caspase-1, cleaved caspase-1, gasdermin D (GSDMD), and GSDMD-N in kidney tissues of rats were determined via western blotting., Results: Dex treatment reduced nephromegaly and serum clinical marker upregulation caused by CP-induced AKI. In addition, hematoxylin and eosin staining revealed that Dex treatment relieved CP-induced kidney tissue injury in AKI rats. ELISA analyses demonstrated that Dex treatment reduced the upregulated levels of proinflammatory cytokines in the kidney tissue of AKI rats induced by CP, thereby alleviating kidney tissue injury. Western blotting indicated that Dex alleviated CP-induced AKI by inhibiting pyroptosis mediated by NLRP-3 and caspase-1., Conclusion: Dex protected rats from CP-induced AKI, and the mechanism may be related to NLRP-3/Caspase-1-mediated pyroptosis.

Background: Acute liver injury is a disease characterized by severe liver dysfunction, caused by significant infiltration of immune cells and extensive cell death with a high mortality. Previous studies demonstrated that the α7 nicotinic acetylcholine receptor (α7nAChR) played a crucial role in various liver diseases. The hypothesis of this study was that activating α7nAChR could alleviate acute liver injury and investigate its possible mechanisms., Methods: Acute liver injury was induced by intraperitoneal injection of lipopolysaccharide (LPS)/D-galactosamine (D-Gal) in wild type, α7nAChR knockout (α7nAChR-/-) and stimulator of interferon gene (STING) mutation (Stinggt/gt) mice in the presence or absence of a pharmacologic selective α7nAChR agonist (PNU-282987). The effects of α7nAChR on hepatic injury, inflammatory response, mitochondrial damage, necroptosis, and infiltration of immune cells during acute liver injury were assessed., Results: The expression of α7nAChR in liver tissue was increased in LPS/D-Gal-induced acute liver injury mice. Compared to the age-matched wild-type mice, α7nAChR deficiency decreased the survival rate, exacerbated the hepatic injury accompanied with enhanced inflammatory response and oxidative stress, and aggravated hepatic mitochondrial damage and necroptosis. Conversely, pharmacologic activation of α7nAChR by PNU-282987 displayed the opposite trends. Furthermore, PNU-282987 significantly reduced the proportion of infiltrating monocyte-derived macrophages (CD45+CD11bhiF4/80int), M1 macrophages (CD45+CD11b+F4/80+CD86hiCD163low), and Ly6Chi monocytes (CD45+CD11b+MHC [major histocompatibility complex] ⅡlowLy6Chi), but increased the resident Kupffer cells (CD45+CD11bintF4/80hiTIM4hi) in the damaged hepatic tissues caused by LPS/D-Gal. Interestingly, α7nAChR deficiency promoted the STING signaling pathway under LPS/D-Gal stimulation, while PNU-282987 treatment significantly prevented its activation. Finally, it was found that Sting mutation abolished the protective effects against hepatic injury by activating α7nAChR., Conclusions: The authors' study revealed that activating α7nAChR could protect against LPS/D-Gal-induced acute liver injury by inhibiting hepatic inflammation and necroptosis possibly via regulating immune cells infiltration and inhibiting STING signaling pathway., (Copyright © 2024 American Society of Anesthesiologists. All Rights Reserved.)

Background & Aims: The precise pathomechanisms underlying the development of non-alcoholic steatohepatitis (NASH, also known as metabolic dysfunction-associated steatohepatitis [MASH]) remain incompletely understood. In this study, we investigated the potential role of EF-hand domain family member D2 (EFHD2), a novel molecule specific to immune cells, in the pathogenesis of NASH., Methods: Hepatic EFHD2 expression was characterized in patients with NASH and two diet-induced NASH mouse models. Single-cell RNA sequencing (scRNA-seq) and double-immunohistochemistry were employed to explore EFHD2 expression patterns in NASH livers. The effects of global and myeloid-specific EFHD2 deletion on NASH and NASH-related hepatocellular carcinoma were assessed. Molecular mechanisms underlying EFHD2 function were investigated, while chemical and genetic investigations were performed to assess its potential as a therapeutic target., Results: EFHD2 expression was significantly elevated in hepatic macrophages/monocytes in both patients with NASH and mice. Deletion of EFHD2, either globally or specifically in myeloid cells, improved hepatic steatosis, reduced immune cell infiltration, inhibited lipid peroxidation-induced ferroptosis, and attenuated fibrosis in NASH. Additionally, it hindered the development of NASH-related hepatocellular carcinoma. Specifically, deletion of myeloid EFHD2 prevented the replacement of TIM4 + resident Kupffer cells by infiltrated monocytes and reversed the decreases in patrolling monocytes and CD4 + /CD8 + T cell ratio in NASH. Mechanistically, our investigation revealed that EFHD2 in myeloid cells interacts with cytosolic YWHAZ (14-3-3ζ), facilitating the translocation of IFNγR2 (interferon-γ receptor-2) onto the plasma membrane. This interaction mediates interferon-γ signaling, which triggers immune and inflammatory responses in macrophages during NASH. Finally, a novel stapled α-helical peptide targeting EFHD2 was shown to be effective in protecting against NASH pathology in mice., Conclusion: Our study reveals a pivotal immunomodulatory and inflammatory role of EFHD2 in NASH, underscoring EFHD2 as a promising druggable target for NASH treatment., Impact and Implications: Non-alcoholic steatohepatitis (NASH) represents an advanced stage of non-alcoholic fatty liver disease (NAFLD); however, not all patients with NAFLD progress to NASH. A key challenge is identifying the factors that trigger inflammation, which propels the transition from simple fatty liver to NASH. Our research pinpointed EFHD2 as a pivotal driver of NASH, orchestrating the over-activation of interferon-γ signaling within the liver during NASH progression. A stapled peptide designed to target EFHD2 exhibited therapeutic promise in NASH mice. These findings support the potential of EFHD2 as a therapeutic target in NASH., (Copyright © 2024 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background: Klebsiella pneumoniae (KP) is the second most prevalent Gram-negative bacterium causing bloodstream infections (BSIs). In recent years, the management of BSIs caused by KP has become increasingly complex due to the emergence of carbapenem-resistant Klebsiella pneumoniae (CRKP). Although numerous studies have explored the risk factors for the development of CRKP-BSIs, the mortality of patients with KP-BSIs, and the molecular epidemiological characteristics of CRKP, the variability in data across different populations, countries, and hospitals has led to inconsistent conclusions. In this single-center retrospective observational study, we utilized logistic regression analyses to identify independent risk factors for CRKP-BSIs and factors associated with mortality in KP-BSI patients. Furthermore, a risk factor-based prediction model was developed. CRKP isolates underwent whole-genome sequencing (WGS), followed by an evaluation of microbiological characteristics, including antimicrobial resistance and virulence genes, as well as epidemiological characteristics and phylogenetic analysis., Results: Our study included a total of 134 patients with KP-BSIs, comprising 50 individuals infected with CRKP and 84 with carbapenem-susceptible Klebsiella pneumoniae (CSKP). The independent risk factors for CRKP-BSIs were identified as gastric catheterization (OR = 9.143; CI = 1.357-61.618; P = 0.023), prior ICU hospitalization (OR = 4.642; CI = 1.312-16.422; P = 0.017), and detection of CRKP in non-blood sites (OR = 8.112; CI = 2.130-30.894; P = 0.002). Multivariate analysis revealed that microbiologic eradication after 6 days (OR = 3.569; CI = 1.119-11.387; P = 0.032), high Pitt bacteremia score (OR = 1.609; CI = 1.226-2.111; P = 0.001), and inappropriate empirical treatment after BSIs (OR = 6.756; CI = 1.922-23.753; P = 0.003) were independent risk factors for the 28-day mortality in KP-BSIs. The prediction model confirmed that microbiologic eradication after 6.5 days and a Pitt bacteremia score of 4.5 or higher were significant predictors of the 28-day mortality. Bioinformatics analysis identified ST11 as the predominant CRKP sequence type, with bla KPC-2 as the most prevalent gene variant. CRKP stains carried multiple plasmid-mediated resistance genes along with some virulence genes. Phylogenetic analysis indicated the presence of nosocomial transmission of ST11 CRKP within the ICU., Conclusions: The analysis of risk factors for developing CRKP-BSIs and the association between KP-BSIs and 28-day mortality, along with the development of a risk factor-based prediction model and the characterization of CRKP strains, enhances clinicians' understanding of the pathogens responsible for BSIs. This understanding may help in the timely administration of antibiotic therapy for patients with suspected KP-BSIs, potentially improving outcomes., (© 2024. The Author(s).)

Heavy metals in farmland soil are one of the most hazardous pollutants in the environment, owing to their universality and irreversibility. Modified biochar has been widely used in the adsorption and immobilization of heavy metals in soil, and its applicability is mainly determined by the types of heavy metals, pollution levels, and soil environmental conditions. Soil pollution is gradually becoming more complex and diversified, and heavy metal pollutants mostly occur in the form of compound pollution. However, most studies have focused on single heavy metal pollutant or the addition of heavy metal to soil. This study used rice straw as a raw material to prepare biochar, and modified it with K 3 PO 4 , KMnO 4 , and NaOH. The physicochemical and structural characteristics of the modified biochars were detected using a BET accelerated surface area and porosimetry system, scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), and the biochars were then analyzed for the availability and forms of Cd and Cu in soils contaminated with heavy metals in the mining area. The results showed that the surface roughness of the modified biochar increased to different degrees with increases in specific surface area and pore volume, with the NaOH modified biochar showing the most significant increases from 4.96 m 2 ·g -1 to 60.79 m 2 ·g -1 , and from 0.02 cm 3 ·g -1 to 0.12 cm 3 ·g -1 , respectively. The pore diameter changed in the opposite direction. The absorption peaks of the functional groups of the modified biochar were all changed, with K 3 PO 4 modified biochar exhibiting the greatest degree of change. The addition of biochar significantly improved the soil pH value ( P <0.05), and the pH value of the soil treated with K 3 PO 4 modified biochar exhibited the largest increase. With an application of 20.5% K 3 PO 4 modified biochar, the availability of Cu and Cd in the soil was significantly reduced, by 75.44% and 67.70%, respectively. The immobilization efficiency of Cu was much higher than that of Cd. The best immobilization efficiency of Cu and Cd in soil was achieved with K 3 PO 4 modified biochar. With an addition of 2% K 3 PO 4 modified biochar, the immobilization efficiency of Cu and Cd was 61.06% and 4.12%, respectively. In summary, K 3 PO 4 modified biochar had a better immobilization effect on both Cu and Cd in compound contaminated soil.

We described a patient with symptomatic giant hepatic hemangioma (GHH) treated with laparoscopic guided percutaneous microwave ablation (MWA). A 58 years' old woman was referred to our hospital who presented with upper abdominal distension and appetite loss for more than 1 year. The medical history included untreated multiple hepatic hemangiomas (HH) that had been detected 13 years ago and hypertension for more than 12 years. Initial laboratory tests revealed D-dimer mild increase and negative tumor markers. Magnetic resonance (MR) imaging demonstrated multiple nodules of different sizes in the liver and the largest lesion was located on the left lobe (longest diameter 12.8 cm), which replaced the whole enlarged left lobe and compressed the gastric body and inferior vena cava. Contrast-enhanced ultrasound (CEUS) and contrast-enhanced MR imaging both showed the typical enhancement pattern of hemangioma and abnormal perfusion was seen in the surrounding liver parenchyma. With the laparoscopy guidance, we performed microwave ablation till the whole tumor was seen atrophy. The total operation duration was 2 hours, with intra-operative blood loss less than 20 ml. The post-operative course was uneventful. The patient was discharged 3 days after the operation. Abdominal distension decreased, appetite improved, blood pressure controlled at normal level after the operation. MR revealed significant volume reduction of the tumor after the operation.

As an important substitute for agarwood, mountain-agarwood, belonging to the family Oleaceae, comes from the root, stem and thick branch of Syringa pinnatifolia, which has a wide range of application in Inner Mongolia, China. It has good clinical efficacy in the use of cardiovascular diseases. However, the formation speed of mountain-agarwood is extremely slow, and its cultivated seedlings have low resin content. Therefore, how to speed up the formation of mountain-agarwood and increase the resin content is a hot research topic in this field. In this work, 16 S rDNA amplicon sequencing method was used to systematically analyze the bacterial communities of different samples of mountain-agarwood. Our data revealed that the samples of mountain-agarwood had more obvious species diversity than the ones of non-mountain-agarwood, especially the wild mountain-agarwood samples. By analysis of bacterial community composition and species abundance, Sphingomonas, Modestobacter and unidentified Cyanobacteria genus were three dominant bacterial genera in all samples. In addition, there are two identified genera of dominant bacteria, namely Actinoplanes and Microbacterium in both wild and cultivated mountain-agarwood, by bacterial community composition and species richness analysis. Meanwhile, Roseomonas was the dominant bacterial genus in both wild and cultivated non-mountain-agarwood samples. Our work could provides basic data for exploring the mechanism of the mountain-agarwood formation, and help to exploit resource of endophytic bacteria reasonably.

Melatonin has been previously shown to prevent nonalcoholic fatty liver disease (NAFLD), yet the underlying mechanisms are poorly understood. Here, we identified a previously unknown regulatory action of melatonin on apoptosis signal-regulating kinase 1 (ASK1) signaling pathway in the pathogenesis and development of NAFLD. Although melatonin administration did not alter food intake, it significantly alleviated fatty liver phenotypes, including the body weight gain, insulin resistance, hepatic lipid accumulation, steatohepatitis, and fibrosis in a high-fat diet (HFD)-induced NAFLD mouse model (in vivo). The protection of melatonin against NAFLD was not affected by inactivation of Kupffer cell in this model. In NAFLD mice liver, ASK1 signal cascade was substantially activated, evidence by the enhancement of total ASK1, phospho-ASK1, phospho-MKK3/6, phospho-p38, phospho-MKK4/7, and phospho-JNK. Melatonin treatment significantly suppressed the ASK1 upregulation and the phosphorylation of ASK1, MKK3/6, MKK4/7, p38, and JNK. Mechanistically, we found that lipid stress triggered the interaction between ASK1 and TNF receptor-associated factors (TRAFs), including TRAF1, TRAF2, and TRAF6, which resulted in ASK1 deubiquitination and thereby increased ASK1 protein stability. Melatonin did not alter ASK1 mRNA level; however, it activated a scaffold protein β-arrestin-1 and enabled it to bind to ASK1, which antagonized the TRAFs-mediated ASK1 deubiquitination, and thus reduced ASK1 protein stability. Consistent with these findings, knockout of β-arrestin-1 in mice partly abolished the protection of melatonin against NAFLD. Taken together, our results for the first time demonstrate that melatonin safeguards against NAFLD by eliminating ASK1 activation via inhibiting TRAFs-mediated ASK1 deubiquitination and stabilization in a β-arrestin-1 dependent manner., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Pt-based nanocomposites with low Pt utilization and high-activity by incorporating with other transition metals have received significant interest in catalysis. Meanwhile, loading Pt-based catalysts on graphene has great research value for improved stability and dispersity of the catalysts. Herein, a facile l-proline-mediated solvothermal strategy was reported to construct reduced graphene oxide (rGO) supported sheet-like PtCo nanocrystals (Pt 78 Co 22 NCs/rGO) in ethylene glycol (EG). The as-synthesized nanocomposite manifested remarkably improved catalytic properties and chemical stability for oxygen reduction reaction (ORR) and hydrogen evolution reaction (HER), surpassing home-made Pt 29 Co 71 nanoparticles (NPs)/rGO, Pt 83 Co 17 NPs/rGO, Pt 52 Co 48 NPs, commercial Pt/C and Pt black catalysts. These scenarios demonstrated an improved catalytic performances by tailoring the feeding ratio of Pt:Co and introducing rGO as a support. This work provides some new insights to design rGO-supported Pt-based catalysts by engineering the shapes and compositions in practical fuel cells., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Herein, highly branched Pt@Ag core-shell nanoparticles (Pt@Ag NPs) were fabricated by a facile one-pot wet-chemical approach, where poly(ethyleneimine) (PEI) served as structure-directing and capping agents. Their structure, morphology and composition were mainly characterized by a set of techniques. And their growth mechanism was discussed in some detail. The prepared catalyst exhibited remarkable enhancement in catalytic activity of 4-nitrophenol (4-NP) reduction as a proof-of-concept application, surpassing commercial Pt black and home-made Ag NPs catalysts. Also, the as-obtained catalyst showed superior stability without sacrificing the catalytic activity. These observations endow the catalyst possibility for practical applications in nitrophenols environmental remediation., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Although laparoscopic common bile duct exploration (LCBDE) has shown many obvious advantages compared with open surgery in the treatment of common bile duct (CBD) stones, it remains unclear regarding risk factors of conversion from LCBDE to open surgery and whether conversion will counteract the advantages of LCBDE. The purpose of this study was to explore risk factors and consequences of conversion from LCBDE to open surgery., Methods: A retrospective study was conducted, using a database of 644 patients with LCBDE between 2011 and 2017. Risk factors for conversion to open surgery were determined based on univariable and multivariable analysis. The consequences of conversion to open surgery in LCBDE were analyzed., Results: Conversion was required in 27 (4.2%) of 644 patients undergoing LCBDE. Independent risk factors for conversion were as follows: the max diameter of stones in CBD (odds ratio (OR) 2.234, 95%CI 1.031-4.842; p = 0.042), edema of CBD (OR 12.530, 95%CI 4.633-33.887; p < 0.001), and multiple stones in CBD (OR 3.438, 95%CI: 1.133-10.428; p = 0.029). These risk factors and their combined were good predictors for conversion in LCBDE. More blood loss, longer operative time, longer postoperative hospital stay, and higher incision infection were identified in patients with conversion than those without conversion. However, no significant differences were observed regarding mortality, readmission within 30 days, reoperation, bile leakage, and intra-abdominal fluid collection., Conclusion: Conversion to open surgery in LCBDE was associated with acute edematous CBD with large and multiple stones. Conversion can offset the advantages of LCBDE.

To establish a robust and accuracy molecular method to identify Achyranthis Bidentatae Radix and Cyathulae Radix formula granules. ITS sequences of Achyranthes bidentata and Cyathula officinalis were aligned, specific SNPs (single nucleotide polymorphisms) were excavated, specific primers were designed and allele-specific PCR method was established. The genomic DNA was successfully extracted from the herbal medicine and its formula granules by using an improved CTAB (cetyltrimethyl ammonium bromide) method and then performed PCR with the designed primers. The 187 bp specific band could be amplified only in the presentation of C. officinalis and its granules when use of C. officinalis specific primers, whereas the 162 bp band could be amplified only in the presentation of A. bidentata and its granules when use of A. bidentata specific primers. This method was also successfully applied in the identification of commercial formula granules., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

The core-shell structure of endohedral fullerenes results in good protection of the encapsulated spin carriers from the environment. In this research, the quantum coherence behavior of the endohedral fullerene Sc 3 C 2 @C 80 in CS 2 solution is characterized from 5 K to room temperature. Below the critical temperature of around 140 K, the inner group is hindered, and the EPR spectrum consists of a single broad line. The spin carriers display a maximum phase memory time of 17.2(7) μs at 10 K. In the high temperature region, the inner group is mobile, and the EPR spectrum consists of 22 homogeneously broadened lines due to isotropic hyperfine coupling. The maximum phase memory time for each transition is around 139(1) ns at 200 K which allows arbitrary superposition state manipulations to be performed. This research demonstrates that Sc 3 C 2 @C 80 displays temperature-crossover behaviour due to weak interaction between the Sc 3 C 2 core and the C 80 shell.

Aim: To investigate a new modification of pancreaticoduodenectomy (PD)-a mesh-like running suturing of the pancreatic remnant and Braun's enteroenterostomy., Methods: Two hundred and three patients underwent PD from 2009 to 2014 and were classified into two groups: Group A (98 patients), who received PD with a mesh-like running suturing for the pancreatic remnant, and Braun's enteroenterostomy; and Group B (105 patients), who received standard PD. Demographic data, intraoperative findings, postoperative morbidity and perioperative mortality between the two groups were compared by univariate and multivariate analysis., Results: Demographic characteristics between Group A and Group B were comparable. There were no significant differences between the two groups concerning perioperative mortality, and operative blood loss, as well as the incidence of the postoperative morbidity, including reoperation, bile leakage, intra-abdominal fluid collection or infection, and postoperative bleeding. Clinically relevant postoperative pancreatic fistula (POPF) and delayed gastric emptying (DGE) were identified more frequently in Group B than in Group A. Technique A (PD with a mesh-like running suturing of the pancreatic remnant and Braun's enteroenterostomy) was independently associated with decreased clinically relevant POPF and DGE, with an odds ratio of 0.266 (95%CI: 0.109-0.654, P = 0.004) for clinically relevant POPF and 0.073 (95%CI: 0.010-0.578, P = 0.013) for clinically relevant DGE., Conclusion: An additional mesh-like running suturing of the pancreatic remnant and Braun's enteroenterostomy during PD decreases the incidence of postoperative complications and is beneficial for patients.

Mesenchymal stem cells (MSCs) can serve as a vehicle for gene therapy. Angiopoietin-1 (ANGPT1) plays an important role in the regulation of endothelial cell survival, vascular stabilization, and angiogenesis. We hypothesized that ANGPT1 gene-modified MSCs might be a potential therapeutic approach for severe acute pancreatitis (SAP) in rats. Human umbilical cord-derived MSCs with or without transfection with lentiviral vectors containing the ANGPT1 gene were delivered through the tail vein of rats 12 h after induction of SAP. Administration of MSCs alone significantly reduced pancreatic injury and inflammation, as reflected by reductions in pancreatitis severity scores and serum amylase and lipase levels as well as reducing the serum levels of proinflammatory cytokines (TNF-α, IFN-γ, IL-1β, and IL-6). Furthermore, administration of ANGPT1-transfected MSCs resulted in not only further reductions in pancreatic injury and serum levels of proinflammatory cytokines, but also promotion of pancreatic angiogenesis. These results suggest that MSCs and ANGPT1 have a synergistic role in the treatment of SAP. ANGPT1 gene-modified MSCs may be developed as a potential novel therapy strategy for the treatment of SAP.

Stromal cell-derived factor-1 (SDF-1) and its receptor, CXC chemokine receptor-4 (CXCR4), are important regulators in the migration of bone marrow mesenchymal stem cells (BMSCs). However, the mechanisms underlying this effect in acute pancreatitis (AP) have not been investigated. In this study, BMSCs were identified by specific cell surface markers and differentiation potentials, and labeled with chloromethylbenzamido-1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (CM-Dil) for in vivo cell tracking. AP was induced by retrograde infusion of sodium taurocholate into the common bile duct in rats. The expression of SDF-1 in the injured pancreas was determined by immunohistochemistry and western blot analysis. BMSCs were incubated with or without anti-CXCR4 antibody and the contribution of SDF-1 to the migration of BMSCs was investigated. Our results demonstrated that the expression of SDF-1 was significantly increased in the injured pancreas, and that these levels peaked on days 5-7 and began to decrease on day 10. SDF-1 induced a dose-dependent migration of BMSCs in an in vitro transwell migration assay, which was almost completely blocked by AMD3100 (CXCR4-specific antagonist) or anti-CXCR4 antibody. In addition, by encouraging the migration of CM-Dil-labeled BMSCs, the SDF-1/CXCR4 axis facilitated the repair of the injured pancreas. This effect was inhibited by the anti-CXCR4 antibody. Taken together, these results indicate that the interaction of locally produced SDF-1 with CXCR4 on BMSCs, has an important regulatory role in the migration of BMSCs towards the injured pancreas in AP.

Aim: To investigate the therapeutic effect of umbilical cord-derived mesenchymal stem cells (UC-MSCs) on rat severe acute pancreatitis (SAP)., Methods: Rats were randomly divided into three groups (n = 15 per group): control group, SAP group, and SAP+MSCs group. SAP was established by retrograde pancreatic duct injection of 3% sodium taurocholate. In SAP+MSCs group, UC-MSCs at 1 × 10(7) cells/kg were injected via the tail vein 12 h after SAP. Rats (n = 5 per group) were sacrificed on days 1, 3 and 5, and the blood and pancreatic tissues were collected. The levels of serum amylase, lipase, inflammatory cytokines, and anti-inflammatory cytokines were determined. Pathological changes of the pancreas (HE staining) and apoptotic acinar cells (TUNEL staining) were observed under light microscope., Results: The levels of serum amylase and lipase in SAP group were significantly higher than those in control group (P<0.05). The pancreas in SAP group showed significantly massive edema, inflammation, hemorrhage and necrosis when compared with control group. There were numerous TUNEL-positive apoptotic acinar cells after SAP. However, in SAP+MSCs group, the levels of serum amylase were significantly reduced on days 1, 3, and 5 after MSC transplantation (P<0.01). The serum lipase level in SAP+MSCs group was significantly lower than that in SAP group on days 3 and 5 (P<0.01). The edema formation, inflammatory cell infiltration, hemorrhage, and necrosis were reduced significantly attenuated in SAP+MSCs group as compared to SAP group (P<0.05). MSCs significantly reduced the levels of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6), but increased the levels of anti-inflammatory cytokines (IL-4 and IL-10) in SAP rats. The number of TUNEL-positive acinar cells was significantly reduced on days 3 and 5 after MSCs transplantation (P<0.01)., Conclusion: Transplantation of UC-MSCs significantly inhibits inflammation and decreases pancreatic injury secondary to SAP.

Various anti-inflammatory agents have been used to treat acute or chronic lung injury-induced pulmonary fibrosis (PF). However, the efficacy of the available treatments is disappointing, and new therapies are urgently needed. In the current study, we investigated the effect of a novel α-melanocyte-stimulating hormone analog, STY39, on bleomycin (BLM)-induced pulmonary inflammation and fibrosis in mice. C57BL/6 mice received an intratracheal injection of BLM before being treated with STY39 (0.625, 1.25, or 2.5 mg/kg, i.p.) once a day for 14 consecutive days. Various parameters, reflecting the inflammatory reaction, metabolism of extracellular matrix, myofibroblast proliferation, and degree of fibrosis in the lung, were evaluated. We found that STY39 significantly improved the survival of mice with lethal BLM-induced lung injury, limited body weight loss and the increase in the lung index, reduced the mRNA expression of types I and III procollagen and the production of hydroxyproline in the lung, diminished myofibroblast proliferation, and ultimately reduced BLM-induced lung damage. Further investigation revealed that, in a dose-dependent manner, STY39 treatment inhibited leukocyte migration into the lung; reduced the production of TNF-α, IL-6, macrophage inflammatory protein 2, and transforming growth factor β1 in the lung; and altered the ratio of matrix metalloproteinase 1 to tissue inhibitors of metalloproteinase 1. These findings suggest that STY39 attenuates BLM-induced experimental PF by limiting the inflammatory reaction through the inhibition of proinflammatory and profibrosis cytokines and by accelerating the metabolism of extracellular matrix. Therefore, STY39 may be an effective therapy for preventing PF.

Aim: To construct the CABYR RNAi plasmid and study its relation with the nuclear factor (NF)-κB signal transduction pathway., Methods: Human CABYR mRNA sequence was obtained from GenBank. The structure of cDNA sequence for the short hairpin RNA was BbsI + sense + loop + antisense + transcription terminator + KpnI + BamHI. A CABYR silencing plasmid was constructed and transfected into the human embryo cell line 293T. Quantitative real-time polymerase chain reaction was used to analyze CABYR and NF-κB gene expression., Results: The CABYR and NF-κB expressions were detected in 293T cells. The oligonucleotide (5'-GCTCAGATGTTAGGTAAAG-3') efficiently silenced the expression of CABYR. The expression of NF-κB was not significantly affected by silencing CABYR (P = 0.743)., Conclusion: CABYR can be found in the human embryo cell line 293T. Cabyrmid 2 can efficiently silence its target, CABYR, indicating that CABYR is not related with the NF-κB signal transduction pathway.

At present, transcription analysis of gene expression commonly uses housekeeping genes as control for normalization. In this study, the expression levels of three housekeeping genes including GAPDH, beta-actin, and 18S rRNA in six tissues and five developmental stages of the Mandarin fish Siniperca chuatsi were assayed with quantitative real-time PCR (qPCR). Differences in expression levels were analyzed using geNorm program. The results demonstrate that beta-actin is the most stable gene at developmental stages and GAPDH is the most stable in different tissues. While 18S rRNA expression during development is differentially regulated, which indicates it is suitable as an internal control for gene expression normalization at the developmental level. Overall, the data suggest that the two most stable housekeeping genes are enough to accurately calibrate gene expression in S. chuatsi. The significance of this study provided convincing references and methodology for housekeeping gene selection and normalization in gene expression analysis with regular PCR or qPCR.

This study proposes an NMR-based metabonomic approach to early prognostic evaluation of sepsis. Forty septic rats receiving cecal ligation and puncture (CLP) were divided into the surviving group and nonsurviving group on day 6, while 20 sham-operated rats served as the control group. Serum samples were collected from septic and sham-operated rats at 12 h after surgery and analyzed using (1)H NMR spectroscopy. Orthogonal partial least squares (OPLS) were applied and showed clustering according to predefined groups, indicating that NMR-based metabolic profiling could reveal pathologic characteristics in the serum of sham-operated, surviving, and nonsurviving septic rats. In addition, six characteristic metabolites including lactate, alanine, acetate, acetoacetate, hydroxybutyrate, and formate, which are mainly involved in energy metabolism, changed markedly in septic rats, especially in the nonsurvivors. Using these metabolites, a predictive model for prognostic evaluation of sepsis was constructed using a radial basis function neural network (RBFNN) with a prediction accuracy of about 87% by test samples. The results indicated that the NMR-based metabonomic approach is a potential technique for the early prognostic evaluation of sepsis., (Copyright (c) 2009 John Wiley & Sons, Ltd.)

A non-suppressed ion chromatographic method by connecting anion-exchange and cation-exchange columns directly was developed for the separation and determination of five inorganic anions (sulfate, nitrate, chloride, nitrite, and chlorate) and three cations (sodium, ammonium, and potassium) simultaneously in explosive residues. The mobile phase was composed of 3.5mM phthalic acid with 2% acetonitrile and water at flow rate of 0.2 mL/min. Under the optimal conditions, the eight inorganic ions were completely separated and detected simultaneously within 16 min. The limits of detection (S/N=3) of the anions and cations were in the range of 50-100 microg/L and 150-320 microg/L, respectively, the linear correlation coefficients were 0.9941-0.9996, and the R.S.D. of retention time and peak area were 0.10-0.29% and 5.65-8.12%, respectively. The method was applied successfully to the analysis of the explosive samples with satisfactory results.

Objectives: Early prognostic evaluation of sepsis is an attractive strategy to decrease the mortality of septic patients, but presently there are no satisfactory approaches. Our goal is to establish an early, rapid and efficient approach for prognostic evaluation of sepsis., Methods: Forty-five septic rats, induced by cecal ligation and puncture, were divided into surviving (n=23) and nonsurviving group (n=22) on day 6. Serum samples were obtained from septic and sham-operated rats (n=25) at 12h after surgery. HPLC/MS assays were performed to acquire serum metabolic profiles, and radial basis function neural network (RBFNN) was employed to build predictive model for prognostic evaluation of sepsis., Results: Principle component analysis allows a clear discrimination of the pathologic characteristics among rats from surviving, nonsurviving and sham-operated groups. Six metabolites related to the outcome of septic rats were then structurally identified, which included linolenic acid, linoleic acid, oleic acid, stearic acid, docosahexaenoic acid and docosapentaenoic acid. A RBFNN model was built upon the metabolic profile data from rat serum, and a high predictive accuracy over 94% was achieved., Conclusions: HPLC/MS-based metabonomic approach combined with pattern recognition permits accurate outcome prediction of septic rats in the early stage. The proposed approach has advantages of rapid, low-cost and efficiency, and is expected to be applied in clinical prognostic evaluation of septic patients.

Two widely documented mechanisms of chloride transport across animal plasma membranes are anion-coupled antiport and sodium-coupled symport. No direct genetic evidence has yet been provided for primary active chloride transport despite numerous reports of cellular CI(-)-stimulated ATPases coexisting, in the same tissue, with uphill chloride transport that could not be accounted for by the two common chloride transport processes. CI(-)-stimulated ATPases are a common property of practically all animal cells, with the major location being of mitochondrial origin. It also appears that the plasma membranes of animal cells are sites of CI(-)-stimulated ATPase activity. Recent studies of CI(-)-stimulated ATPase activity and chloride transport in the same membrane system, including liposomes, suggest a mediation by the ATPase in net movement of chloride up its electrochemical gradient across animal plasma membranes. Further studies, especially from a molecular biological perspective, are required to confirm a direct transport role to plasma membrane-localized Cl(-)-stimulated ATPases.