Metabolic-related gene signatures for survival prediction and immune cell subtypes associated with prognosis in intrahepatic cholangiocarcinoma.

OBJECTIVES: Our study aimed to reveal the metabolic-related gene signatures for survival prediction and immune cell subtypes associated with IHCC prognosis. METHODS: Differentially expressed metabolic genes were identified between survival group and dead group which were divided according to survival at discharge. Recursive feature elimination (RFE) and randomForest (RF) algorithms were applied to optimize the combination of feature metabolic genes, which were used to generate SVM classifier. Performance of SVM classifier was evaluated by receiver operating characteristic (ROC) curves. Gene set enrichment analysis (GSEA) was conducted to uncover the activated pathways in high risk group, and differences in immune cell distributions were revealed. RESULTS: There were 143 differentially expressed metabolic gens. RFE and RF identified 21 overlapping differentially expressed metabolic genes, and the constructed SVM classifier had excellent accuracy in training and validation dataset. RS survival prediction model was consisted of 10 metabolic genes. RS model had reliable predictive capability in the training and validation dataset. GSEA revealed 15 significant KEGG pathways that were relatively activated in the high risk group. High risk group had obviously lower counts of B cell naive and T cell CD4+ memory resting, while higher counts of B cell plasma and macrophage M2. CONCLUSION: Prognostic prediction model of 10 metabolic genes could accurately predict the prognosis of IHCC patients.

Electrical Sympathetic Neuromodulation Protects Bone Marrow Niche and Drives Hematopoietic Regeneration during Chemotherapy.

The sympathetic nervous system (SNS) of the bone marrow regulates the regeneration and mobilization of hematopoietic stem cells. Chemotherapy can damage bone marrow SNS, which impairs hematopoietic regeneration and aggravates hematologic toxicities. This leads to long-term bone marrow niche damage and increases mortality in patients undergoing chemotherapy. Electrical neuromodulation has been used to improve functional recovery after peripheral nerve injury. This study demonstrates that electrical sympathetic neuromodulation (ESN) of bone marrow can protect the bone marrow niche from chemotherapy-induced injury. Using carboplatin-treated rats, the SNS via the sciatic nerve innervating the femoral marrow with the effective protocol for bone marrow sympathetic activation is electrically stimulated. ESN can mediate several hematopoietic stem cells maintenance factors and promote hematopoietic regeneration after chemotherapy. It also activates adrenergic signals and reduces the release of pro-inflammatory cytokines, particularly interleukin-1 ß, which contribute to chemotherapy-related nerve injury. Consequently, the severity of chemotherapy-related leukopenia, thrombocytopenia, and mortality can be reduced by ESN. As a result, in contrast to current drug-based treatment, such as granulocyte colony-stimulating factor, ESN can be a disruptive adjuvant treatment by protecting and modulating bone marrow function to reduce hematologic toxicity during chemotherapy.

Panax notoginseng saponins prevent colitis-associated colorectal cancer via inhibition IDO1 mediated immune regulation.

Colorectal cancer (CRC) is the third most lethal cancer and leading cause of cancer mortality worldwide. A key driver of CRC development is colon inflammatory responses especially in patients with inflammatory bowl disease (IBD). It has been proved that Panax notoginseng saponins (PNS) have anti-inflammatory, anti-oxidant and anti-tumor effects. The chemopreventive and immunomodulatory functions of PNS on colitis-associated colorectal cancer (CAC) have not been evaluated.This present study was designed to study the potential protective effects of PNS on AOM/DSS-induced CAC mice to explore the possible mechanism of PNS against CAC. Our study showed that PNS significantly alleviated colitis severity and prevented the occurrence of CAC. Functional assays revealed that PNS relieved immunosuppression of Treg cells in the CAC microenvironment by inhibiting the expression of IDO1 mediated directly by signal transducer and activator of transcription 1 (STAT1) rather than phosphorylated STAT1. Ultimately, Rh1, one of the PNS metabolites, exhibited the best inhibitory effect on IDO1 enzyme activity. Our study showed that PNS exerted significant chemopreventive function and immunomodulatory properties on CAC. It could reduce macrophages accumulation and Treg cells differentiation to reshape the immune microenvironment of CAC. These findings provided a promising approach for CAC intervention.

Undifferentiated embryonal sarcoma of the liver with epithelioid features in an adult patient: A case report.

INTRODUCTION: Undifferentiated embryonal sarcoma of the liver (UESL) is a rare form of liver malignancy, with most cases reported in the pediatric population. This disease is extremely uncommon in adults. Herein, we report the first case of UESL with epithelioid features in an adult patient. PATIENT CONCERNS: A 50-year-old man was admitted to our hospital due to epigastric pain. DIAGNOSIS AND INTERVENTIONS: Computed tomography and magnetic resonance imaging revealed a space-occupying lesion in the right lobe of the liver. A right hemihepatectomy was performed. Postoperative pathological and immunohistochemical examinations confirmed the diagnosis of UESL and features of epithelioid differentiation. OUTCOMES: The patient recovered well and refused adjuvant therapy. Unfortunately, the patient died of tumor recurrence 3 months after hospital discharge. CONCLUSION: UESL is a rare form of liver cancer, with most cases reported in the pediatric population. This case study highlights an extremely uncommon case of UESL with epithelioid features and a very poor prognosis. The findings suggest that complete intraoperative resection and postoperative adjuvant therapy should be considered to improve the prognosis of adult patients with UESL with epithelioid features.

First Report of Seedling Stem Rot on Jinxianlian (Anoectochilus roxburghii) Caused by Fusarium oxysporum in China.

Anoectochilus roxburghii is an important Chinese herbal medicine plant belonging to Orchidaceae and known as Jinxianlian. This orchid is cultivated and mostly adopted to treat diabetes and hepatitis. About 2 billion artificially cultivated seedlings of Jinxianlian are required each year and approximately $600 million in fresh A. roxburghii seedlings is produced in China. From 2011, sporadic occurrence of stem rot on Jinxianlian have been observed in greenhouses in Jinhua City (N29°05', E119°38'), Zhejiang Province. In 2018, nearly 30% of seedlings of Jinxianlian grown in greenhouse conditions were affected by stem rot in Jinhua City. Symptoms initially occurred in the stem at the soil line causing dark discoloration lesions, rotted tissues, wilting, and eventually leading to the death of the plants. A total of 23 diseased seedlings collected from seven different greenhouses were surface sterilized with 1.5% sodium hypochlorite for 3 min, then rinsed in water. Pieces of tissues disinfected from each sample were plated on 2% potato dextrose agar (PDA), and incubated at 25°C in the dark for 5 days (Kirk et al. 2008). A total of 19 isolates were recovered. They developed colonies with purple mycelia and beige or orange colors after 7 days of incubation under 25°C on PDA and carnation leaf agar (CLA) media (Kirk et al. 2008; Zhang et al. 2016). Colonies on PDA had an average radial growth rate of 3.1 to 4.0 mm /d at 25°C. Colony surface was pale vinaceous, floccose with abundant aerial mycelium. On CLA, aerial mycelium was sparse with abundant bright orange sporodochia forming on the carnation leaves. Microconidia were hyaline and oval-ellipsoid to cylindrical (3.7 to 9.3 × 1.3 to 2.9 µm) (n=19). Macroconidia were 3 to 5 septate and fusoid-subulate with a pedicellate base (27.4 to 35.6 × 3.2 to 4.2 µm) (n=19). These morphological features were consistent with Fusarium oxysporum (Sun et al. 2008; Lombard et al., 2019). To confirm the identification based on these morphological features, the internal transcribed spacer region (ITS) and translation elongation factor1 (TEF) were amplified from the DNA of 3 out of 19 isolates chosen at random respectively using the set primer ITS1/ITS4 and EF1/ EF2 (Sun, S., et al. 2018; Lombard et al., 2019). BLAST analysis revealed that the ITS sequences (OK147619, OK147620, OK147621) had 99% identity to that of F. oxysporum isolate JJF2 (GenBank MN626452) and TEF sequence (OK155999, OK156000, OK156001) had 100% identity to that of F. oxysporum isolate gss100 (GenBank MH341210). A multilocus phylogenetic analysis by Bayesian inference (BI) and maximum likelihood (ML) trees based on ITS and TEF indicated that the pathogen grouped consistently with F. oxysporum. Three out of 19 isolates chosen at random were selected to evaluate pathogenicity. Uninfected healthy A. roxburghii seedlings about 40 day-old planted in sterilized substrates were sprayed with distilled water containing 2 x 106 conidia per ml suspensions as inoculums, and plants sprayed with distilled water alone served as controls. Plants were then incubated at 25°C and 85% relative humidity. Ten plants were inoculated for each isolate. After 10 days, all plants inoculated developed stem rot symptoms, while control plants remained healthy. Cultures of Fusarium spp. were re-isolated only from inoculated plants with the frequency of 100% and re-identified by morphological characteristics as F. oxysporum, fulfilling Koch's postulates. To the best of our knowledge, this is the first report of F. oxysporum causing stem rot on A. roxburghii seedlings. As F. oxysporum is a devastating pathogenic fungus with a broad host range, measures should be taken in advance to manage stem rot of A. roxburghii.

Surface Epitaxial Nano-Topography Facilitates Biomineralization to Promote Osteogenic Differentiation and Osteogenesis.

Biomimetic modification of hydroxyapatite on a polymer surface is a potent strategy for activating biological functions in bone tissue engineering applications. However, the polymer surface is bioinert, and it is difficult to introduce a uniform calcium phosphate (CaP) layer. To overcome this limitation, we constructed a specific nano-topographical structure onto a poly(ε-caprolactone) substrate via surface-directed epitaxial crystallization. Formation of the CaP layer on the nano-topological surface was enhanced by 2.34-fold compared to that on a smooth surface. This effect was attributed to the abundant crystallization sites for CaP deposition because of the increased surface area and roughness. Bone marrow mesenchymal stromal cells (BMSCs) were used to examine the biological effect of biomineralized surfaces. We clearly demonstrated that BMSCs responded to surface biomineralization. Osteogenic differentiation and proliferation of BMSCs were significantly promoted on the biomineralized nano-topological surface. The expression of alkaline phosphatase and osteogenic-related genes as well as extracellular matrix mineralization was significantly enhanced. The proposed strategy shows potential for designing bone repair scaffolds.

[Preliminary study on memory function of Sorbus aucuparia suspension cell to biotic stress].

Plants have a memory function for the environmental stress they have suffered. When they are subjected to repeated environmental stress, they can quickly and better activate the response and adaptation mechanism to environmental stress, thus realizing long-term stable reproduction. However, most of the relevant studies are applied to crops and Arabidopsis thaliana rather than medicinal plants about the improvement of plant growth status and the effect on phytoalexin biosynthesis. In this study, yeast extract(YE) was used as an elicitor to simulate biotic stress, and the changes in biomass and the content of some secondary metabolites were measured by giving repeated stresses to Sorbus aucuparia suspension cell(SASC). The results showed that the accumulation levels of biomass and some secondary metabolites in SASC subjected to repeated stress are significantly increased at some time points compared with single stress. A phenomenon that SASC can memorize biotic stress is confirmed in this study and influences phytoalexin accumulation in SASC. Furthermore, the work laid the groundwork for research into the transgenerational stress memory mechanism of medicinal plant.

Novel dibenzofuran and biphenyl phytoalexins from Sorbus pohuashanensis suspension cell and their antimicrobial activities.

Two novel sulfur-containing dibenzofurans, sorbusins A (1) and B (2), two unprecedented biphenyl glycosides, 2'-hydroxyaucuparin 2'-O-ɑ-L-rhamnoside (3) and noraucuparin 5-O-ɑ-L-rhamnoside (4), and four known analogues (5-8), were isolated from Sorbus pohuashanensis suspension cell induced by yeast extract. Their structures were elucidated based on spectroscopic analyses and quantum calculation of 13C NMR data. Structurally, compound 1 possessed a rare naturally occurring benzothiazole moiety and represents the first example of thiazole fused dibenzofuran. A plausible biosynthetic pathway for the sulfur-containing dibenzofurans is proposed. These dibenzofuran and biphenyl phytoalexins were evaluated for their antimicrobial activities against pathogenic fungi and drug-resistant bacteria. Compound 7 exhibited significant antibacterial activity against methicinllin-resistant Staphylococcus aureus with an MIC value of 3.13 µg/mL.

Highly improved aqueous lubrication of polymer surface by noncovalently bonding hyaluronic acid-based hydration layer for endotracheal intubation.

Hydration lubrication is the key responsible for the exceptionally low boundary friction between biosurfaces. However, it is a challenge to settle a hydration layer on a polymer surface via a noncovalent manner. Herein, we develop a highly lubricated coating absorbed onto the polymer surface via intermolecular association of hyaluronic acid (HA)-based micelles. A poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) triblock copolymer (Pluronic, F127) is recruited to complex with HA and further self-assembled to form a thick micelle layer. High water-retaining capacity of the HA/F127 coating enables the decorated surface with excellent hydrophilicity and boundary lubrication, where the coefficient of friction in aqueous media is reduced by 60% compared with the bare polymer surface. The HA/F127 coating suppresses nonspecific protein adsorption and exhibits good biocompatibility. More remarkably, an in vivo cynomolgus monkey model, demonstrates the utility of the HA/F127 coating in alleviating or preventing complications of endotracheal intubation, such as foreign irritation, airway mucosal damage, and inflammatory response. This cost-effective and scalable approach is suitable to manufacture interventional devices especially disposable medical devices with highly lubricated surface.

Endoscopic Nasogallbladder Drainage Combined with Laparoscopic Surgery for Type I Mirizzi Syndrome with Acute Cholecystitis: A Case Series Report.

OBJECTIVE: To investigate the safety and feasibility of endoscopic nasogallbladder drainage (ENGBD) combined with laparoscopic surgery for Mirizzi syndrome type I with acute cholecystitis. METHODS: An analysis of 4 patients with type I Mirizzi syndrome with acute cholecystitis admitted to the First Hospital of Jilin University. RESULTS: The patients underwent ENGBD, and laparoscopic surgery was evaluated postoperatively. All four patients successfully recovered from this combined surgical approach. CONCLUSION: The combination of ENGBD and laparoscopic surgery is safe and feasible for the treatment of patients with type I Mirizzi syndrome accompanied by acute cholecystitis. This approach may reduce the traumatic stress on patients and is worthy of widespread implementation.

Corrigendum: The ATP-P2X7 Signaling Axis Is an Essential Sentinel for Intracellular Clostridium difficile Pathogen-Induced Inflammasome Activation.

[This corrects the article DOI: 10.3389/fcimb.2018.00084.].

Group A Streptococcus Subcutaneous Infection-Induced Central Nervous System Inflammation Is Attenuated by Blocking Peripheral TNF.

Group A streptococcus (GAS) infection causes a strong inflammatory response associated with cytokine storms, leading to multiorgan failure, which is characterized as streptococcal toxic shock syndrome. However, little is known about GAS subcutaneous infection-mediated brain inflammation. Therefore, we used a bioluminescent GAS strain and reporter mice carrying firefly luciferase under transcriptional control of the nuclear factor-kappa B (NF-κB) promoter to concurrently monitor the host immune response and bacterial burden in a single mouse. Notably, in addition to the subcutaneous inoculation locus at the back of mice, we detected strong luminescence signals from NF-κB activation and increased inflammatory cytokine production in the brain, implying the existence of central nervous system inflammation after GAS subcutaneous infection. The inflamed brain exhibited an increased expression of glial fibrillary acidic protein and nicotinamide adenine dinucleotide phosphate oxidase components and greater microglial activation and blood-brain barrier (BBB) disruption. Furthermore, Fluoro-Jade C positive cells increased in the brain, indicating that neurons underwent degeneration. Peripheral tumor necrosis factor (TNF), which contributes to pathology in brain injury, was elevated in the circulation, and the expression of its receptor was also increased in the inflamed brain. Blockage of peripheral TNF effectively reduced brain inflammation and injury, thereby preventing BBB disruption and improving survival. Our study provides new insights into GAS-induced central nervous system inflammation, such as encephalopathy, which can be attenuated by circulating TNF blockage.

[Jasmonate signal pathway involved in phytoalexin biosynthesis in Sorbus aucuparia cell elicited by Hpa1].

The Harpin protein Hpa1 can induce defense responses in plant. This study aimed at investigating the role of jasmonate (JA) signal pathway in the process of biosynthesis of secondary metabolite in Sorbus aucuparia cell eliciting by Hpa1 crude extract (Hpa1 CE). The results showed that Hpa1 crude extract (Hpa1 CE) could induce phytoalexin synthesis in S. aucuparia cell， most of which was noraucuparin and its glycosides. Meanwhile Hpa1 CE treatment resulted in methyl jasmonate (MeJA) production increased and noraucuparin was de novo synthesized in large quantities. Combination of Hpa1 CE and salicylhydroxamic acid (SHAM, JA signaling inhibitor) caused the decreased MeJA and noraucuparin in the S. aucuparia cell compared with that in Hpa1 CE group. Real-time PCR results indicated that Hpa1 CE treatment caused down-regulation of JAZ and up-regulation of mcy2 in transcription level. Therefore Hpa1 CE elicited defense mechanism and JA signaling pathway involved in phytoalexin biosynthesis in S. aucuparia cell. It presented information to elucidate the role of JA signal pathway in stress response in the perspective of secondary metabolism of plant.

The ATP-P2X7 Signaling Axis Is an Essential Sentinel for Intracellular Clostridium difficile Pathogen-Induced Inflammasome Activation.

Clostridium difficile infection (CDI) is the leading cause of nosocomial infection in hospitalized patients receiving long-term antibiotic treatment. An excessive host inflammatory response is believed to be the major mechanism underlying the pathogenesis of C. difficile infection, and various proinflammatory cytokines such as IL-1ß are detected in patients with C. difficile infection. IL-1ß is known to be processed by caspase-1, a cysteine protease that is regulated by a protein complex called the inflammasome, which leads to a specialized form of cell death called pyroptosis. The function of inflammasome activation-induced pyroptosis is to clear or limit the spread of invading pathogens via infiltrated neutrophils. Here, we focused on inflammasome activation induced by intact C. difficile to re-evaluate the nature of inflammasome activation in CDI pathogenesis, which could provide information that leads to an alternative therapeutic strategy for the treatment of this condition in humans. First, we found that caspase-1-dependent IL-1ß production was induced by C. difficile pathogens in macrophages and increased in a time-dependent manner. Moreover, intracellular toxigenic C. difficile was essential for ATP-P2X7 pathway of inflammasome activation and subsequent caspase-1-dependent pyroptotic cell death, leading to the loss of membrane integrity and release of intracellular contents such as LDH. Notably, we also observed that bacterial components such as surface layer proteins (SLPs) were released from pyroptotic cells. In addition, pro-IL-1ß production was completely MyD88 and partially TLR2 dependent. Finally, to investigate the role of the caspase-1-dependent inflammasome in host defense, we found that colonic inflammasome activation was also induced by CDI and that caspase-1 inhibition by Ac-YVAD-CMK led to increased disease progression and C. difficile load. Taken together, the present results suggest that MyD88 and TLR2 are critical component in pro-IL-1ß production and intracellular C. difficile following the ATP-P2X7 pathway of inflammasome activation and pyroptosis, which play important roles in host defense through the utilization of inflammation-mediated bacterial clearance mechanisms during C. difficile infection.

[Assessment of soil fertility for cultivation of Chinese herbal medicines].

The soil fertility has great impacts on the yielding of Chinese medicinal materials, as well as the generation of major components. The practices showed that soil fertility has been decayed with the growth of cultivation years,which is leading to adverse effect on quality and quantity of Chinese medicinal materials. However, there was a lack of domestic unified standard for assessment of soil fertility of Chinese medicinal material cultivation, which has seriously limited the soil management and quality control. In this text, we reviewed the progress on research of soil fertility evaluation, built the soil fertility evaluation index including soil texture,soil bulk density,soil organic matter,soil acidity and alkalinity,soil available nitrogen,soil available phosphorus, soil available potassium,soil animals and soil microorganisms. It would provide the direction and thought for standard-settin on soil fertility evaluation of Chinese medicinal material cultivation.

A new family of 1D, 2D and 3D frameworks aggregated from Ni5, Ni4 and Ni7 building units: synthesis, structure, and magnetism.

Three new Ni(ii)-clusters based on a Y-shaped ligand (biphenyl-3,4',5-tricarboxylate, H3BPT), [Ni5(HBPT)4(OH)2(H2O)12]n (), [Ni4(BPT)2(OH)2(H2O)6]n·4nH2O (), and [Ni7(BPT)2(1,4-bib)2(OH)6(HCO2)2]n·3nH2O () (1,4-bib = 1,4-bi(1H-imidazol-1-yl)benzene), have been synthesized under solvothermal conditions. They were studied by infrared spectroscopy (IR), single crystal X-ray diffraction, thermogravimetric analysis (TGA), and magnetochemistry. The complexes contain low nuclear Ni-clusters as building units (BUs). Structurally, in , the cluster BUs of [Ni5(µ3-OH)2](8+) can be viewed as two reverse triangles sharing a common vertex, which are connected by the partially deprotonated µ2-η(1):η(1)-HBPT(2-) forming 1D chains. The BUs of [Ni4(µ3-OH)2](6+) clusters in can be considered as two reverse triangles sharing a common edge and extended by deprotonated µ6-η(1):η(1):η(1):η(1):η(2)-BPT(3-) constructing a 2D framework. The 3D framework of complex consists of a [Ni7(µ3-OH)4(R-COO)7(HCO2)3] cluster BUs with fully deprotonated µ5-η(1):η(1):η(1):η(1):η(1):η(1)-BPT(3-) and 1,4-bib ligands. In addition, TGA reveals that the complexes are stable in the range of 293-548 K. Magnetostructural analyses indicate ferromagnetic coupling of J1 = 1.85(3) and J2 = 2.25(4) cm(-1) in and J = 5.76(6) cm(-1) in , whereas magnetic parameters J1 = -2.64(3), J2 = -23.22(19) and J3 = 12.02(5) cm(-1) indicate an alternating magnetic chain (AF/F) in .

Quantitative PPARγ expression affects the balance between tolerance and immunity.

PPARγ modulates energy metabolism and inflammation. However, its specific functions in the balance of immunity in vivo have been explored incompletely. In this study, by the age of 14 mo, Pparg(C/-) mice with PPARγ expression at 25% of the normal level exhibited high autoantibody levels and developed mesangial proliferative glomerulonephritis, which resembled systemic lupus erythematosus (SLE)-like autoimmune disease. These symptoms were preceded by splenomegaly at an early age, which was associated with increases in splenocyte accumulation and B-cell activation but not with relocation of hematopoiesis to the spleen. The mechanism of splenic lymphocyte accumulation involved reduced sphingosine-1-phosphate receptor 1 (S1P1) expression and diminished migration toward S1P in the Pparg(C/-) splenocytes, which impeded lymphocyte egression. Mechanistically, increased Th17 polarization and IL-17 signaling in the Pparg(C/-) CD4(+) T cells contributed to B-cell hyperactivation in the spleen. Finally, the activation of the remaining PPARγ in Pparg(C/-) mice by pioglitazone increased S1P1 levels, reduced the Th17 population in the spleen, and ameliorated splenomegaly. Taken together, our data demonstrated that reduction of Pparg expression in T-helper cells is critical for spontaneous SLE-like autoimmune disease development; we also revealed a novel function of PPARγ in lymphocyte trafficking and cross talk between Th17 and B cells.

A three-dimensional mixed-valence Cu(II)/Cu(I) coordination polymer constructed from biphenyl-3,4',5-tricarboxylate and 1,4-bis(1H-imidazol-1-yl)benzene ligands.

Coordination polymers (CPs) built by coordination bonds between metal ions/clusters and multidentate organic ligands exhibit fascinating structural topologies and potential applications as functional solid materials. The title coordination polymer, poly[diaquabis(µ4-biphenyl-3,4',5-tricarboxylato-κ(4)O(3):O(3'):O(4'):O(5))tris[µ2-1,4-bis(1H-imidazol-1-yl)benzene-κ(2)N(3):N(3')]dicopper(II)dicopper(I)], [Cu(II)2Cu(I)2(C15H7O6)2(C12H10N4)3(H2O)2]n, was crystallized from a mixture of biphenyl-3,4',5-tricarboxylic acid (H3bpt), 1,4-bis(1H-imidazol-1-yl)benzene (1,4-bib) and copper(II) chloride in a water-CH3CN mixture under solvothermal reaction conditions. The asymmetric unit consists of two crystallographically independent Cu atoms, one of which is Cu(II), while the other has been reduced to the Cu(I) ion. The Cu(II) centre is pentacoordinated by three O atoms from three bpt(3-) ligands, one N atom from a 1,4-bib ligand and one O atom from a coordinated water molecule, and the coordination geometry can be described as distorted trigonal bipyramidal. The Cu(I) atom exhibits a T-shaped geometry (CuN2O) coordinated by one O atom from a bpt(3-) ligand and two N atoms from two 1,4-bib ligands. The Cu(II) atoms are extended by bpt(3-) and 1,4-bib linkers to generate a two-dimensional network, while the Cu(I) atoms are linked by 1,4-bib ligands, forming one-dimensional chains along the [20-1] direction. In addition, the completely deprotonated µ4-η(1):η(1):η(1):η(1) bpt(3-) ligands bridge one Cu(I) and three Cu(II) cations along the a (or [100]) direction to form a three-dimensional framework with a (10(3))2(10)2(4(2).6.10(2).12)2(4(2).6.8(2).10)2(8) topology via a 2,2,3,4,4-connected net. An investigation of the magnetic properties indicated a very weak ferromagnetic behaviour.

Anti-proliferative and pro-apoptotic activities of Alpinia oxyphylla on HepG2 cells through ROS-mediated signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Fructus Alpiniae oxyphyllae (A. oxyphylla) is a traditional herb which is widely used in East Asian for the treatment of dyspepsia, diarrhea, abdominal pain, poor memory, inflammatory conditions and cancer. MATERIALS AND METHODS: The cytotoxic activities of ethanol extract (EE) and five extract layers including petroleum ether (PE), dichloromethane (DCLM), acetoacetate (EtOAc), n-Butanol (n-Bu) and water fractions (WF) of A. oxyphylla were tested on HepG2, SW480, MCF-7, K562 and HUVEC cell lines using MTT assay and LDH release assay. The component analysis was performed on HPLC with gradient elution. Hoechst 33342 staining, DCFH-DA fluorescence microscopy, flow cytometry analysis, western blot and migration assays were carried out to determine the anti-cancer mechanisms of PE. RESULTS: MTT analysis showed that EE, PE and DCLM could inhibit cell proliferation on HepG2, SW480, MCF-7, K562 and HUVEC cell lines, especially PE fraction. HPLC analysis pointed out five main components which may contribute to the anti-proliferative activity of PE. Further study showed that PE increased LDH release, induced apoptosis, disrupted mitochondrial membrane potential and elevated intracellular reactive oxygen species (ROS) in HepG2 cells, whereas the antioxidant N-acetyl-l-cysteine (NAC) prevented PE-induced ROS generation. The results of western blot revealed that PE induced apoptosis in HepG2 cells by enhancing Bax/Bcl-2 ratio, increasing cytochrome c in cytosol and activating caspase-3/9. Meanwhile, high levels of ROS could induce DNA damage-mediated protein expression, AKT, ERK inactivation and SAPKs activation. Furthermore, PE conspicuously blocked the migration of HUVEC cells. CONCLUSION: The present results demonstrated that PE induced apoptosis in HepG2 cells may be via a ROS-mediated signaling pathway.

Proton-Pump Inhibitor Exposure Aggravates Clostridium difficile-Associated Colitis: Evidence From a Mouse Model.

BACKGROUND: Clostridium difficile is currently the leading cause of infectious diarrhea in hospitalized patients. In addition to the infection due to toxigenic C. difficile in the gastrointestinal tract of susceptible hosts, other predisposing factors for C. difficile infection (CDI) are identified, including advanced age, a prolonged hospital stay, and use of acid-suppressive drugs. Of note, exposure to gastric acid-reducing agents, such as H2 blockers and proton pump inhibitors (PPIs), remains a controversial risk factor, and has been associated with CDI in some studies but not in others. A mouse model of antibiotic-associated clostridial colitis was established to examine the role of PPIs for CDI. MATERIALS AND METHODS: A mouse model of antibiotic-associated clostridial colitis was set up. NF-κB reporter mice were used to address the in vivo spatial and temporal inflammatory patterns of C. difficile-associated colitis. Serum levels of lipopolysaccharide and dextran-FITC were measured to reflect the barrier permeability of affected intestines. RESULTS: Mice with CDI that were exposed to PPI exhibited greater losses of stool consistency and body and cecal weights than those that were not exposed to PPI. Further, more neutrophilic infiltrations, epithelial damage, and inflammatory cytokine expression were noted in colon specimens of the mice with PPI exposure. More-evident inflammatory responses were detected by in vivo imaging of NF-κB reporter mice with CDI that were exposed to PPI. Gut barrier permeability was increased to a greater extent, as reflected by higher serum levels of lipopolysaccharide and dextran-FITC in mice with CDI that were exposed to PPI. CONCLUSIONS: Our mouse model demonstrates that PPI exposure increases the severity of intestinal inflammation in mice with C. difficile-associated colitis.