Translation of nonclinical to clinical safety findings for 27 biotherapeutics.

Human adverse drug reactions (ADRs), and in vivo nonclinical adverse and nonadverse findings, were identified in 27 biotherapeutic programs and placed into organ categories to determine translation. The sensitivity of detecting human ADRs was 30.8% with a positive predictive value (PPV) of 53.3% for nonclinical adverse findings; sensitivity increased to 67.3% and PPV fell to 35.0% when including nonadverse findings. Nonclinical findings were associated with a greater likelihood of a human ADR in that organ category, especially for adverse findings [positive likelihood ratio (LR+) >10 (lower 95% confidence interval [CI] of >5)]. The specificity and negative predictive value (NPV) were very high (>85%). A lack of nonclinical findings in an organ category was associated with a lower likelihood of a human ADR in that organ category. About 40-50% of human ADRs and nonclinical adverse findings, and about 30% of nonclinical nonadverse findings, were attributed to pharmacology. Slightly more than half of the human ADRs with a translating nonclinical finding had findings in animals that could be considered very similar. Overall, 38% of nonclinical findings translated to a human ADR at the organ category level. When nonclinical findings did not translate to humans, the cause was usually higher exposures or longer dosing in animals. All programs with human ADRs attributed to immunogenicity also had nonclinical adverse or nonadverse findings related to immunogenicity. Overall, nonclinical adverse and nonadverse findings were useful in predicting human ADRs, especially at an organ category level, and the majority of human ADRs were predicted by nonclinical toxicity studies.

Rapid Oxidative Detoxification of Mustard Simulant by the Multisite Synergistic Catalytic Action of {PMoVI11MoVO40CuI8} Units.

Under hydrothermal and solvent-thermal conditions, we synthesized two novel polyoxometalate (POM)-based hybrids: [CuI4(Pz)2(H2O)8(PMoVI11MoVO40)]·3.5H2O (1, Pz = pyrazine) and [(C2H8N)5(HPMoVI9MoV3O40)]·DMF·4H2O (2). Single-crystal X-ray diffraction indicates that compound 1 is a three-dimensional structure consisting of Cu (I), {PMo12} anions, Pz, and water, where Cu (I) can be considered as Lewis acid sites. Furthermore, both compounds 1 and 2 possess favorable catalysis activity in catalyzing the conversion of chemical warfare agent simulant 2-chloroethylethyl sulfide (CEES) to nontoxic production of 2-chloroethylethyl sulfoxide (CEESO) under ambient temperature. Significantly, 1 could realize 98% conversion and 100% selectivity of CEES owing to the multisite synergy in the {PMoVI11MoVO40CuI8} units in which the tricoordinated Cu (I) could interact with S and O atoms from CEES and H2O2, respectively. This interaction not only decreases the distance of CEES from peroxomolybdenum species formed by H2O2 but also activates CEES.

Exploring Electron Transfer Mechanism in Synergistic Interactional Reduced Polyoxometalate-Based Cu(I)-Organic Framework for Photocatalytic Removal of U(VI).

Photocatalytic reduction of U(VI) is a promising method for removing uranium containing pollutants. However, using polyoxometalate-based metal-organic frameworks (POMOFs) for photoreduction of U(VI) is rare, and the relevant charge transfer pathway is also not yet clear. In this article, we demonstrate a highly efficient strategy and revealed a clearly electron transfer pathway for the photoreduction of U(VI) with 99% removal efficiency by using a novel POMOF, [Cu(4,4'-bipy)]5·{AsMo4VMo6VIV2VO40(VIVO)[VIVO(H2O)]}·2H2O (1), as catalyst. The POMOF catalyst was constructed by the connection of reduced {AsMo10V4} clusters and Cu(I)-MOF chains through Cu-O coordination bonds, which exhibits a broader and stronger light absorption capacity due to the presence of reduced {AsMo10V4} clusters. Significantly, the transition of electrons from Cu(I)-MOF to {AsMo10V4} clusters (Cu → Mo/V) greatly inhibits the recombination of photogenerated carriers, thereby advancing electron transfer. More importantly, the {AsMo10V4} clusters are not only adsorption sites but also catalytically active sites. This causes the fast transfer of photogenerated electrons from Mo/V to UO22+(Mo/V → O → U) via the surface oxygen atoms. The shorter electron transmission distance between catalytic active sites and UO22+ achieves faster and more effective electron transport. All in all, the highly effective photocatalytic removal of U(VI) using the POMOF as a catalyst is predominantly due to the synergistic interaction between Cu(I)-MOFs and reduced {AsMo10V4} clusters.

Concentrations, seasonal trends, sources, health risk and subchronic toxicity to the respiratory and immune system of PAHs in PM2.5 in Xi'an.

PM2.5-bound polycyclic aromatic hydrocarbons (PAHs) have been proved to be hazardous to health. Previous studies have focused on the distribution and sources of PAHs, whereas there is little knowledge of the damage to organs. Here we sought to investigate the pollution level and seasonal variation characteristics of PAHs in PM2.5 in Xi'an and assess the health risk, to establish a PAHs exposure model, and investigate the toxicological effects of PAHs on the respiratory and immune functions. A sub-chronic exposure model of PAHs was established by inhalation. The pathological changes of lung tissues were observed with a light microscope. Inflammatory reactions in alveolar lavage fluid were determined using the corresponding kit. The levels of interleukin-6 (IL-6) and interleukin-8 (IL-8) were detected with enzyme linked immunosorbent assay (ELISA) kit; the proliferation of lymphocytes in spleen was detected with methyl tetrazolium (MTT); DNA immune damage was determined with DNA gel electrophoresis. The results showed that (1) the total concentration of 16 PAHs ranged from 41.1 to 387 ng/m3, with a mean value of 170 ng/m3, and the concentration of PAHs in PM2.5 was higher in winter than in other seasons. (2) The sources of PAHs in the atmosphere of Xi'an urban area were mainly coal combustion, and the equivalent carcinogenic concentration of PAHs in PM2.5 was 3.9 ng/m3. (3) Foreign body granuloma formation and inflammatory cell damage were observed in the lungs of rats infected with toxin; the levels of reactive oxygen species (ROS) and mobile device assistant (MDA) increased while nitric oxide synthase (NOS) decreased with the increase of dose; the expression levels of IL-6 and IL-8 elevated with the increase of toxin dose, showing an obvious dose-effect relationship; the level of PAHs damage to cells showed a dose-effect relationship. Sub-chronic exposure to PAHs could cause sustained inflammatory injury to the organism. Measures should be taken to counter the problems of PAHs in PM2.5 in Xi'an and relevant health promotion strategies should be developed.

Progress in the Application of Magnetic Nanoparticles in Forensic Trace Analysis.

Given the complexity of biological samples and the trace nature of target materials in forensic trace analysis, a simple and effective method is needed to obtain sufficient target materials from complex substrates. Magnetic nanoparticles (MNPs) have shown a wide range of application value in many research fields, such as biomedicine, drug delivery and separation, due to their unique superparamagnetic properties, stable physical and chemical properties, biocompatibility, small size, high specific surface area and other characteristics. To apply MNPs in the pretreatment of forensic materials, maximize the extraction rate of the target materials, and minimize interference factors to meet the requirements of trace analysis of the target materials, this paper reviews the application of MNPs in the fields of forensic toxicological analysis, environmental forensic science, trace evidence analysis and criminal investigation in recent years, and provides research ideas for the application of MNPs in forensic trace analysis.

Revisiting the multi-mechanism hypothesis of part-list cuing: the role of list-length and item presentation time.

When defining the associative encoding, the multi-mechanism hypothesis of part-list cuing does not heed the effect of list length and item presentation time. Through four experiments, this study first proved that short list length and long item presentation time were the boundary conditions of the part-list cuing effects (Experiment 1). Then, it was further found that under a shorter list length, no matter whether the study context was accessed or not, both the detrimental and beneficial effects of part-list cuing were absent (Experiment 2). While under a longer list length and shorter item presentation time, when access to the study context was maintained, part-list cuing impaired recall and when context access was impaired, part-list cuing facilitated memory retrieval (Experiment 3). Finally, adopting a simplified experimental paradigm, the stability of significant detrimental and beneficial effect in Experiment 3 was further verified (Experiment 4). The findings showed that the effects of part-list cuing have boundary conditions, that is, the impairment and facilitation effect of part-list cuing are constrained by list length and item presentation time, which is a key supplement to the multi-mechanism hypothesis about when the impairment and facilitation effect occurs.

Occurrence, Molecular Characterization, and Antibiotic Resistance of Cronobacter sakazakii in Goat Milk-Based Infant Formula from Shaanxi Province, China.

This study aimed to investigate the prevalence of Cronobacter sakazakii in goat milk-based infant formula (GIF) collected from Shaanxi Province, China, and reveal the molecular characterization and antibiotic resistance profile of these isolates. A total of 750 GIF samples were collected from the retail markets in 5 cities in Shaanxi Province from February 2019 to February 2021. Molecular characterization was investigated using multilocus sequence typing and O-antigen serotyping. Antibiotic resistance of C. sakazakii isolates was assessed using antimicrobial susceptibility testing. Thirty-two strains of C. sakazakii were isolated from GIF samples with a prevalence rate of 4.27% and were divided into 16 sequence types (STs); among them, ST4 (6/32, 18.75%) and ST21 (5/32, 15.63%) were dominant. Five C. sakazakii serotypes (O2, O1, O7, O4, and O3) were detected, and C. sakazakii serotype O2 (15/32, 46.88%) was the main. Of the 21 antimicrobials, isolates showed higher resistance against cephalothin (87.5%), amoxicillin (25%), azithromycin (18.75%), oxytetracycline (18.75%), ampicillin (12.5%), and streptomycin (12.5%). In addition, three isolates were found to be resistant to three antimicrobials. These findings revealed the potential epidemiological risk and characterization of C. sakazakii in GIF from Shaanxi Province, China, and provided reference data for the effective prevention and control of C. sakazakii in powdered infant formula.

Antibacterial Effect of Chrysanthemum Buds' Crude Extract Against Salmonella Typhimurium and Potential Application in Cooked Chicken.

The objective of this study was to clarify the antibacterial activity and mechanism of Chrysanthemum buds' crude extract (CBCE) against Salmonella Typhimurium, and explore the potential application in cooked chicken. The zone of inhibition (ZI), minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC) were used to assess the in vitro antibacterial activity of CBCE against Salmonella Typhimurium. The antibacterial mechanism was elucidated by revealing the changes in intracellular adenosine 5'-triphosphate (ATP) concentration, membrane potential, content of biomacromolecule, and cell morphology. Furthermore, the effect of CBCE on the counts of Salmonella Typhimurium and color of cooked chicken during storage was studied. The results showed that the ZI, MIC, and MBC of CBCE against Salmonella Typhimurium were 12.9 ± 0.53-13.6 ± 0.14 mm, 40, and 80 mg/mL, respectively. In the process of inhibiting Salmonella Typhimurium by CBCE, the reduction of intracellular ATP concentration, cell membrane depolarization, leakage of protein and nucleic acid, and destruction of cell morphology were observed. Moreover, after treatments with CBCE, the growth of Salmonella Typhimurium in cooked chicken was significantly inhibited (p < 0.05) compared with the control group. No significant differences (p > 0.05) in lightness (L*), redness (a*), and yellowness (b*) values of cooked chicken were found between untreated and treated samples, as well as the color of cooked chicken treated with CBCE did not change significantly (p > 0.05) during the six days of storage. Overall, our findings suggested that CBCE exhibited the antibacterial effect against Salmonella Typhimurium, and had the potential to be used as a natural food preservative for the control of Salmonella Typhimurium in chicken products.

Genotyping, Antimicrobial Susceptibility and Biofilm Formation of Bacillus cereus Isolated from Powdered Food Products in China.

This study was conducted to reveal the genotyping, antimicrobial susceptibility, and biofilm formation of Bacillus cereus isolated from powdered food products in China. Five hundred powdered food samples were collected from five provinces in China: 100 samples each of powdered infant formula (PIF), soy milk powder (SMP), lotus root powder (LRP), walnut powder (WP), and rice flour (RF). The genotyping of isolates was analyzed using multilocus sequence typing; meanwhile, antimicrobial susceptibility, and ability of biofilms formation on stainless steel tube of isolates were evaluated. Forty-two B. cereus strains were detected with an overall contamination rate of 8.4%, as well as, the highest B. cereus contamination rate was found in SMP (10%), followed by LRP (9%), WP (9%), RF (8%), and PIF (6%). These isolates were divided into 22 sequence types (STs); among them, ST32 (4/42, 9.5%) was the predominant ST. Phylogenetic relationships showed that the 42 strains of B. cereus were divided into three groups (group I, group II, and group III). Antimicrobial susceptibility testing indicated that all isolates were susceptible to tetracycline, gentamicin, erythromycin, and chloramphenicol, while resistant to ampicillin, cefepime, oxacillin, and rifampin. The analysis of ability of biofilm formation on stainless steel tube showed optical density (OD)595 value of 66.7% of B. cereus isolates was greater than 1. The OD595 level of isolates belonging to group III was higher compared with the other two groups, and OD595 values of B. cereus HB1 and HN5 were greater than 2. These findings improved the understanding of the characteristics of B. cereus isolated from powdered food products in China, and provided a theoretical basis for the prevention and control of B. cereus in food industry.

A Europium-based MOF Fluorescent Probe for Efficiently Detecting Malachite Green and Uric Acid.

Lanthanide (such as Tb and Eu) metal-organic frameworks (MOFs) have been widely used in fluorescent probes because of their multiple coordination modes and brilliant fluorescence characteristic. Many lanthanide MOFs were applied in detecting metal ions, inorganic anions, and small molecules. However, it's rarely reported that Ln-MOF was devoted to detecting malachite green (MG) and uric acid (UA). We prepared a europium-based metal-organic framework (Eu-TDA) (TDA = 2,5-thiophenedicarboxylic acid group). Luminescence studies demonstrated that Eu-TDA can rapidly detect MG and UA with excellent selectivity and sensitivity, where individual quenching efficiency Ksv (MG: 5.8 × 105 M-1; UA: 4.15 × 104 M-1) and detection limit (MG: 0.0221 µM; UA: 0.689 µM) were regarded as the excellent MOF sensors for detecting MG and UA. The quenching of Eu-TDA's fluorescence emission by MG and UA was likely due to the spectral overlap, energy transfer, and competition. Among 11 metal cations and 14 anions, Eu-TDA can quickly and effectively recognize MG and UA with highly selective and sensitive properties. Our method possesses potential application in detecting UA in human blood and MG in the fishpond.

Platelet deposition estimation: A novel method for emulating the pump thrombosis potential of blood pumps.

Pump thrombosis potential exists in most blood pumps and limits their clinical use. To improve the pump thrombosis performance of blood pumps, a method for emulating the platelet deposition on the flow passage component surfaces inside blood pumps was presented and tested. The method emulates the blood platelet deposition, employing laser-induced fluorescence tracing technology. The blood pump was rotated in a mock circulation loop with deionized water filled with fluorescent particles. The component surfaces were then explored via laser. The fluorescent particles were induced by laser and imaged in a charge-coupled device (CCD) camera to show the distribution of fluorescent particles gathering on the blood pump component surfaces. The activated platelet deposition was emulated by fluorescent particle gathering. The experiment showed obvious particle gathering on the interface surfaces and cross-sectional surface (perpendicular to the flow). This platelet deposition estimation (PDE) method can be easily incorporated in the in vitro testing phase to analyze and decrease a pump's thrombosis potential before animal experimentation, thereby reducing the cost of blood pump development. This methodology of emulating blood platelet deposition indicates its potential for improving flow passage component structure and reducing device thrombosis of blood pumps.

Amaranthus tricolor crude extract inhibits Cronobacter sakazakii isolated from powdered infant formula.

The purpose of this study was to elucidate the antibacterial activity and possible mechanism of action of Amaranthus tricolor crude extract (ATCE) against Cronobacter sakazakii isolated from powdered infant formula (PIF). The antibacterial activity of ATCE was assessed by measuring the diameter of inhibition zone (DIZ), minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC). The possible mechanism of action of ATCE was revealed by analyzing the effects of ATCE on growth curves and changes in cell membrane potential, intracellular pH, content of bacterial protein and genomic DNA, and cell morphology. Finally, ATCE was applied to the disinfection of C. sakazakii in biofilm on stainless steel tube. The results showed that the DIZ, MIC, and MBC of ATCE against C. sakazakii strains were from 14.35 ± 0.67 to 14.84 ± 0.67 mm, 20 mg/mL, and 40 mg/mL, respectively. Treatment with ATCE ended the logarithmic growth phase of C. sakazakii, and led to depolarization of the cell membranes, reducing intracellular pH and bacterial protein and genomic DNA contents, and resulting in cytoplasmic leakage and deformation. In addition, ATCE effectively inactivated C. sakazakii in biofilm, reducing viable bacteria by approximately 6.5 log cfu/mL bacterial count after treatment with 1 MIC (1 MIC = 20 mg/mL) of ATCE for 20 min at 25°C. Our findings showed that ATCE inactivated C. sakazakii strains isolated from PIF and has potential as a natural disinfectant to reduce the contamination of PIF by C. sakazakii.

[Airway epithelial cells increase macrophage chemotaxis and inflammatory cytokine secretion under hypoxic conditions].

OBJECTIVE: To investigate the effects of airway epithelial cells on macrophages chemotaxis and inflammatory cytokine expression under hypoxic conditions.
 Methods: Human bronchial epithelial cells (HBE) treated with different concentrations (0, 100, 200, 400, 800 µmol/L) of CoCl2 or transfected with HIF-1α siRNA were co-cultured with THP-1-derived M1 macrophages or M2 macrophages. The chemotactic effects on macrophages were analyzed by Transwell assay. The levels of TNF-α, IFN-γ, IL-4, IL-13 and IL-10 in the supernatants of macrophages were detected by ELISA, and HIF-1α or Cav-1 mRNA expression in HBE or macrophages was detected by RT-qPCR.
 Results: HBE cells promoted macrophages chemotaxis in a time- and concentration-dependent manner. Compared to un-transfected group, the chemotactic ability of HBE transfected with HIF-1α siRNA was significantly weakened (P<0.01). Under the same culture conditions, the chemotaxis of M2 macrophages was greater than that in THP1-derived M1 macrophages. The concentrations of TNF-α, IFN-γ, IL-4, IL-13 and IL-10 in the supernatants of macrophages were increased in a time-and concentration-dependent manner. The concentrations of TNF-α and IFN-γ were increased further after co-culturing for 8 and 12 h; while IL-4, IL-13 and IL-10 concentrations were increased further during 24 h of co-culture. The levels of cytokines in the supernatants of macrophages co-cultured with HBE and transfected with HIF-1α siRNA were significantly lower than those in un-transfected cells (P<0.05 or P<0.01). The reduction of TNF-α or IFN-γ was more obvious. The expression of HIF-1α or Cav-1 mRNA in HBE or macrophages was increased in a concentration-dependent manner after 8 or 12 h co-culture, which was significantly reduced when HBE was transfected with HIF-1α siRNA.
 Conclusion: Airway epithelial cells can enhance macrophages chemotaxis and pro-inflammatory cytokines expressions under hypoxic condition. HIF-1α and Cav-1 may be the important mediators in these processes.

Microwave assisted digestion followed by ICP-MS for determination of trace metals in atmospheric and lake ecosystem.

The study of trace metals in the atmosphere and lake water is important due to their critical effects on humans, aquatic animals and the geochemical balance of ecosystems. The objective of this study was to investigate the concentration of trace metals in atmospheric and lake water samples during the rainy season (before and after precipitation) between November and December 2015. Typical methods of sample preparation for trace metal determination such as cloud point extraction, solid phase extraction and dispersive liquid-liquid micro-extraction are time-consuming and difficult to perform; therefore, there is a crucial need for development of more effective sample preparation procedure. A convection microwave assisted digestion procedure for extraction of trace metals was developed for use prior to inductively couple plasma-mass spectrometric determination. The result showed that metals like zinc (133.50-419.30µg/m3) and aluminum (53.58-378.93µg/m3) had higher concentrations in atmospheric samples as compared to lake samples before precipitation. On the other hand, the concentrations of zinc, aluminum, chromium and arsenic were significantly higher in lake samples after precipitation and lower in atmospheric samples. The relationship between physicochemical parameters (pH and turbidity) and heavy metal concentrations was investigated as well. Furthermore, enrichment factor analysis indicated that anthropogenic sources such as soil dust, biomass burning and fuel combustion influenced the metal concentrations in the atmosphere.

Description of Sphingomonas mohensis sp. nov., Isolated from Sediment.

An aerobic, gram-reaction-negative, rod-shaped bacterium, designated strain Z6(T), was isolated from sediment collected at Mohe Basin, China. And its taxonomic position was investigated by applying a polyphasic approach. Growth occurs at 10-45 °C (optimum, 30 °C), at pH 6.0-11.0 (optimum, pH 7.0) and in the presence of 0-3.0 % (w/v) NaCl (optimum, 0 %). The polar lipid profile of strain Z6(T) revealed the presence of diphosphatidylglycerol, phosphatidylethanolamine, sphingoglycolipid and two unidentified phospholipids, and the major quinone was Q-10. The major fatty acids were C18:1 ω7c and/or C18:1 ω6c (summed feature 8) and C16:1 ω6c and/or C16:1 ω7c (summed feature 3). The predominant polyamine was homospermidine. The DNA G + C content of strain Z6(T) is 65.2 mol%. On the basis of the polyphasic evidence presented, strain Z6(T) represents a novel species of the genus Sphingomonas, for which the name Sphingomonas mohensis sp. nov. is proposed. The type strain is Z6(T) (=CGMCC 1.12891(T) = JCM 19983(T)).

Dyadobacter sediminis sp. nov., isolated from a subterranean sediment sample.

A Gram-reaction-negative, flexirubin-type-pigmented, rod-shaped, aerobic, non-motile bacterium, designated strain Z12(T), was isolated from a subsurface sediment sample. In a phylogenetic tree based on 16S rRNA gene sequences, strain Z12(T) formed a distinct clade with the members of the genus Dyadobacter (<96.7 % sequence similarity). The G+C content of genomic DNA was 45.4 %. The major fatty acids of strain Z12(T) were iso-C15 : 0, C16 : 1ω6c and/or C16 : 1ω7c (summed feature 3) and anteiso-C17 : 1 B and/or iso-C17 : 1 I (summed feature 4). The major respiratory quinone was MK-7 and the major polar lipid was phosphatidylethanolamine. On the basis of phenotypic, phylogenetic and genotypic features, strain Z12(T) is considered to represent a novel species, for which the name Dyadobacter sediminis sp. nov., is proposed. The type strain is Z12(T) ( = JCM 30073(T) = CGMCC 1.12895(T)).

Dual effects of atmospheric pressure plasma jet on skin wound healing of mice.

Cold plasma has become an attractive tool for promoting wound healing and treating skin diseases. This article presents an atmospheric pressure plasma jet (APPJ) generated in argon gas through dielectric barrier discharge, which was applied to superficial skin wounds in BALB/c mice. The mice (n = 50) were assigned randomly into five groups (named A, B, C, D, E) with 10 animals in each group. Natural wound healing was compared with stimulated wound healing treated daily with APPJ for different time spans (10, 20, 30, 40, and 50 seconds) on 14 consecutive days. APPJ emission spectra, morphological changes in animal wounds, and tissue histological parameters were analyzed. Statistical results revealed that wound size changed over the duration of the experimental period and there was a significant interaction between experimental day and group. Differences between group C and other groups at day 7 were statistically significant (p < 0.05). All groups had nearly achieved closure of the untreated control wounds at day 14. The wounds treated with APPJ for 10, 20, 30, and 40 seconds showed significantly enhanced daily improvement compared with the control and almost complete closure at day 12, 10, 7, and 13, respectively. The optimal results of epidermal cell regeneration, granulation tissue hyperplasia, and collagen deposition in histological aspect were observed at day 7. However, the wounds treated for 50 seconds were less well healed at day 14 than those of the control. It was concluded that appropriate doses of cold plasma could inactivate bacteria around the wound, activate fibroblast proliferation in wound tissue, and eventually promote wound healing. Whereas, over doses of plasma suppressed wound healing due to causing cell death by apoptosis or necrosis. Both positive and negative effects may be related to the existence of reactive oxygen and nitrogen species (ROS and RNS) in APPJ.

Effects of combined therapy with glipizide and Aralia root bark extract on glycemic control and lipid profiles in patients with type 2 diabetes mellitus.

BACKGROUND: The root bark of Aralia is a rich source of bioactive components that may improve glycemic control and lipid status. In this study, 148 patients with type 2 diabetes mellitus (T2DM) were assigned randomly to receive either glipizide alone or glipizide plus Aralia root bark extract (ARBE) for 8 weeks to test the effects of ARBE plus glipizide therapy on glycemic control and lipid profiles in these patients. RESULTS: Levels of HbA1c, fasting plasma glucose (FPG) and 2 h postprandial plasma glucose (2-h PPG) in both groups significantly decreased from baseline. Glycated hemoglobin (HbA1c) decreased marginally significantly in participants taking glipizide plus ARBE compared with the glipizide group (P = 0.06). Participants in the combination group had significant decreases in total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), and the between-group difference achieved statistical significance for LDL-C (P = 0.04). Reduction in HbA1c in the combination group was significantly associated with changes in TC (r = 0.32; P = 0.006) and LDL-C (r = 0.34; P = 0.005), and the change in FPG was inversely correlated with LDL-C reduction (r = 0.34; P = 0.004). CONCLUSIONS: In patients with T2DM, combination therapy with glipizide and ARBE resulted in moderately lowering HbA1c and LDL-C levels compared with glipizide alone.

Moheibacter sediminis gen. nov., sp. nov., a member of the family Flavobacteriaceae isolated from sediment, and emended descriptions of Empedobacter brevis, Wautersiella falsenii and Weeksella virosa.

A Gram-reaction-negative, yellow-pigmented, strictly aerobic bacterium, designated M0116T, was isolated from the sediment of the Mohe Basin in north-east China. Flexirubin-type pigments were produced. Cells were catalase- and oxidase-positive and non-gliding rods. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain M0116T was a member of the family Flavobacteriaceae and was most closely related to members of the genera Empedobacter, Wautersiella and Weeksella with 90.5-91.0% sequence similarities. The major cellular fatty acids were iso-C15:0 and iso-C17:0 3-OH. The major respiratory quinone was MK-6 and the major polar lipid was phosphatidylethanolamine. The DNA G+C content was 38.2 mol%. Based on phenotypic, phylogenetic and genotypic data, strain M0116T is considered to represent a novel species of a new genus in the family Flavobacteriaceae, for which the name Moheibacter sediminis gen. nov., sp. nov. is proposed. The type strain is M0116T (=CGMCC 1.12708T=JCM 19634T). Emended descriptions of Empedobacter brevis, Wautersiella falsenii and Weeksella virosa are also proposed.

[Effect of Qufeng Tongluo Recipe on the expressions of connexin 36 protein and gene in rat mesangial cells].

OBJECTIVE: To determine the effect of Qufeng Tongluo Recipe (QFTLR) on the expressions of connexin 36 (Cx36) protein and gene in rat mesangial cells (MCs) and the proliferation of the MCs. METHODS: Serum samples containing Benazepril (Bena) and QFTLR were prepared in line with serum pharmacology methodology. The MCs cultured in vitro were divided into normal control and Lipopolysaccharide (LPS), Bena and QFTLR treated groups. The expressions of Cx36 protein and gene were detected by laser scanning confocal microscope (LSCM), Western blot, immunohistochemical assay and quantitative real time polymerase chain reaction (QRT-PCR) respectively. RESULTS: Compared with the control, higher level of Cx36 protein expression was found in the MCs than treated with LPS (P < 0.01). Both Bena and QFTLR lowered the level of Cx36 protein expression in the MCs treated with LPS significantly (P < 0.01 or P < 0.05). Similar results were found with the expression of Cx36 mRNA. CONCLUSION: QFTLR inhibits the proliferation of rat MCs, possibly through down-regulating the expressions of Cx36 protein and gene.