Vesicular Stomatitis Virus (VSV) G Glycoprotein Can Be Modified to Create a Her2/Neu-Targeted VSV That Eliminates Large Implanted Mammary Tumors.

Viral oncolytic immunotherapy is a nascent field that is developing tools to direct the immune system to find and eliminate cancer cells. Safety is improved by using cancer-targeted viruses that infect or grow poorly on normal cells. The recent discovery of the low-density lipoprotein (LDL) receptor as the major vesicular stomatitis virus (VSV) binding site allowed for the creation of a Her2/neu-targeted replicating recombinant VSV (rrVSV-G) by eliminating the LDL receptor binding site in the VSV-G glycoprotein (gp) and adding a sequence coding for a single chain antibody (SCA) to the Her2/neu receptor. The virus was adapted by serial passage on Her2/neu-expressing cancer cells resulting in a virus that yielded a 15- to 25-fold higher titer following in vitro infection of Her2/neu+-expressing cell lines than that of Her2/neu-negative cells (~1 × 108/mL versus 4 × 106 to 8 × 106/mL). An essential mutation resulting in a higher titer virus was a threonine-to-arginine change that produced an N-glycosylation site in the SCA. Infection of Her2/neu+ subcutaneous tumors yielded >10-fold more virus on days 1 and 2 than Her2/neu- tumors, and virus production continued for 5 days in Her2/neu+ tumors compared with 3 days that of 3 days in Her2/neu- tumors. rrVSV-G cured 70% of large 5-day peritoneal tumors compared with a 10% cure by a previously targeted rrVSV with a modified Sindbis gp. rrVSV-G also cured 33% of very large 7-day tumors. rrVSV-G is a new targeted oncolytic virus that has potent antitumor capabilities and allows for heterologous combination with other targeted oncolytic viruses. IMPORTANCE A new form of vesicular stomatitis virus (VSV) was created that specifically targets and destroys cancer cells that express the Her2/neu receptor. This receptor is commonly found in human breast cancer and is associated with a poor prognosis. In laboratory tests using mouse models, the virus was highly effective at eliminating implanted tumors and creating a strong immune response against cancer. VSV has many advantages as a cancer treatment, including high levels of safety and efficacy and the ability to be combined with other oncolytic viruses to enhance treatment results or to create an effective cancer vaccine. This new virus can also be easily modified to target other cancer cell surface molecules and to add immune-modifying genes. Overall, this new VSV is a promising candidate for further development as an immune-based cancer therapy.

Achieving High-Temperature Phosphorescence by Organic Cocrystal Engineering.

Organic phosphors offer a promising alternative in optoelectronics, but their temperature-sensitive feature has restricted their applications in high-temperature scenarios, and the attainment of high-temperature phosphorescence (HTP) is still challenging. Herein, a series of organic cocrystal phosphors are constructed by supramolecular assembly with an ultralong emission lifetime of up to 2.16 s. Intriguingly, remarkable stabilization of triplet excitons can also be realized at elevated temperature, and green phosphorescence is still exhibited in solid state even up to 150 °C. From special molecular packing within the crystal lattice, it has been observed that the orientation of isolated water cluster and well-controlled molecular organization via multiple interactions can favor the structural rigidity of cocrystals more effectively to suppress the nonradiative transition, thus resulting in efficient room-temperature phosphorescence and unprecedented survival of HTP.

Enhanced Photocatalytic Activity of π-Conjugated Pyridine Rings-Modified C3N4/Bi@BiOCl Z-Scheme Heterogeneous Material.

The enhanced photocatalytic properties of Z-Scheme Bi@BiOCl/C3N4-DPY heterojunction materials were successfully prepared by the ultrasonic-assisted coprecipitation method. The Bi@BiOCl/C3N4-DPY heterojunction exhibited remarkable photocatalytic activity under visible light irradiation, and the degradation rate of methyl orange (MO) was about 90.6% in 180 min. This impressive efficiency is mainly due to the Z-Scheme charge transfer mechanism in Bi@BiOCl/C3N4-DPY, resulting in the efficient separation of charge carriers and an increase in the REDOX potential of photogenerated electrons and holes. C3N4 was modified with a π-deficient conjugated pyridine ring, which caused the light absorption redshift, promoted the formation of oxidizing •O2-, and improved the photocatalytic activity. At the same time, a well-aligned heterojunction is formed at the interface between C3N4-DPY and BiOCl, facilitating the seamless transfer of light-induced electrons from the LUMO of C3N4-DPY to the CB of BiOCl. In addition, the addition of Bi introduces a unique band gap reduction effect, resulting in a change in the density of the band states, which further promotes charge transfer and separation. It is worth noting that the introduction of metallic bismuth (Bi) brings about a unique band gap reduction effect, resulting in a change in the density of states within the band, which ultimately promotes charge transfer and separation. The Z-scheme charge migration inside Bi@BiOCl/C3N4-DPY further promotes the efficient separation of photogenerated electron-hole pairs, greatly improving the overall efficiency of the material. The Z-structured photocatalyst developed in this study has great application potential in various fields of photocatalysis.

Supercooled Liquids with Dynamic Room Temperature Phosphorescence Using Terminal Hydroxyl Engineering.

Dynamic room temperature phosphorescence (RTP) materials have potential applications in optoelectronics, which inevitably suffer from poor processability, flexibility or stretchability. Herein, we report a concise strategy to develop supercooled liquids (SCLs) with dynamic RTP behavior using terminal hydroxyl engineering. The terminal hydroxyls effectively hinder the nucleation process of molecules for the formation of stable SCLs after thermal annealing. Impressively, the SCLs show reversible RTP emission via alternant stimulation by UV light and heat. Photoactivated SCLs have phosphorescent efficiency of 8.50 % and a lifetime of 31.54 ms under ambient conditions. Regarding the dynamic RTP behavior and stretchability of SCLs, we demonstrate the applications in erasable data encryption and patterns on flexible substrates. This finding provides a design principle for obtaining SCLs with RTP and expands the potential applications of RTP materials in flexible optoelectronics.

Sirt6 regulates autophagy in AGE-treated endothelial cells via KLF4.

BACKGROUND AND AIMS: High glucose and its byproducts are important factors causing dysfunction of endothelial cells. Autophagy is critical for endothelial cellular homeostasis. However, the specific molecular mechanism of how autophagy is regulated in endothelial cells under high-glucose condition remains unknown. We aim to explore the role Sirt6 plays in regulating autophagy in AGE-treated endothelial cells and how this function is exerted via KLF4. METHODS AND RESULTS: Our results indicate that autophagy level increased in AGE-treated endothelial cells alongside with higher Sirt6 and KLF4 expression level. What's more, knock-in of Sirt6 by adenovirus led to augmented autophagy level while knockdown of Sirt6 led to the opposite. We also verified that Sirt6 affected KLF4 expression positively but KLF4 didn't influence Sirt6 expression level while knocking out of KLF4 impaired Sirt6-enhanced autophagy. Finally we found that STZ-induced diabetic mice showed more autophagosomes in endothelium and Sirt6 knockdown by adeno-associated virus reduced the number of autophagosomes. Knockdown of Sirt6 also caused impaired endothelium integrity but echocardiography indicated there were no significant functional differences. CONCLUSION: Our research reveals more about how Sirt6 regulates autophagy in endothelial cells under high-glucose simulated condition and provides further insight into the relationships between Sirt6 and KLF4.

Endophytic Bacteria Associated with Medicinal Plant Vernonia anthelmintica: Diversity and Characterization.

Increasing evidence shows that endophytic bacteria living inside plant tissue may possess similar biological activity and produce similar metabolites to their hosts. This study aimed to determine the diversity of endophytic bacteria associated with Vernonia anthelmintica and to evaluate their biological activity. The bacteria were isolated from the plant tissue using culture-dependent techniques. Comparison of the 16S rRNA gene sequences of endophytic bacteria isolated from V. anthelmintica showed that isolates belong to the species Micrococcus endophyticus VERA1, Bacillus megaterium VERA2, Pseudomonas chlororaphis VERA3, P. kilonensis VERA4, Stenotrophomonas pavanii VERA5, B. endophyticus VERA6, S. maltophilia VERA7, Pantoea ananatis VERA8, B. atrophaeus VERA9 and M. flavus VERA10. Activity studies showed that the endophytic bacteria share several similar biological properties with their host plant including antimicrobial, anti-vitiligo and antidiabetic activities. These findings indicate that plant phytochemical compounds and activity play an important role in the physiological properties of their endophytes.

Optimization of Scorpion Protein Extraction and Characterization of the Proteins' Functional Properties.

Scorpion has long been used in traditional Chinese medicine, because whole scorpion body extract has anti-cancer, analgesic, anti-thrombotic blood anti-coagulation, immune modulating, anti-epileptic, and other functions. The purpose of this study was to find an efficient extraction method and investigate some of physical and chemical parameters, like water solubility, emulsification, foaming properties, and oil-holding capacity of obtained scorpion proteins. Response surface methodology (RSM) was used for the determination of optimal parameters of ultrasonic extraction (UE). Based on single factor experiments, three factors (ultrasonic power (w), liquid/solid (mL/g) ratio, and extraction time (min)) were used for the determination of scorpion proteins (SPs). The order of the effects of the three factors on the protein content and yield were ultrasonic power > extraction time > liquid/solid ratio, and the optimum conditions of extraction proteins were as follows: extraction time = 50.00 min, ultrasonic power = 400.00 w, and liquid/solid ratio = 18.00 mL/g. For the optimal conditions, the protein content of the ultrasonic extraction and yield were 78.94% and 24.80%, respectively. The solubility, emulsification and foaming properties, and water and oil holding capacity of scorpion proteins were investigated. The results of this study suggest that scorpion proteins can be considered as an important ingredient and raw material for the creation of water-soluble supramolecular complexes for drugs.

Expression and characteristics of manganese peroxidase from Ganoderma lucidum in Pichia pastoris and its application in the degradation of four dyes and phenol.

BACKGROUND: Manganese peroxidase (MnP) of white rot basidiomycetes, an extracellular heme enzyme, is part of a peroxidase superfamily that is capable of degrading the different phenolic compounds. Ganoderma, a white rot basidiomycete widely distributed worldwide, could secrete lignin-modifying enzymes (LME), including laccase (Lac), lignin peroxidases (LiP) and MnP. RESULTS: After the selection of a G. lucidum strain from five Ganoderma strains, the 1092 bp full-length cDNA of the MnP gene, designated as G. lucidum MnP (GluMnP1), was cloned from the selected strain. We subsequently constructed an eukaryotic expression vector, pAO815:: GlMnP, and transferred it into Pichia pastoris SMD116. Recombinant GluMnP1 (rGluMnP1) was with a yield of 126 mg/L and a molecular weight of approximately 37.72 kDa and a specific enzyme activity of 524.61 U/L. The rGluMnP1 could be capable of the decolorization of four types of dyes and the degradation of phenol. Phenol and its principal degradation products including hydroquinone, pyrocatechol, resorcinol, benzoquinone, were detected successfully in the experiments. CONCLUSIONS: The rGluMnP1 could be effectively expressed in Pichia pastoris and with a higher oxidation activity. We infer that, in the initial stages of the reaction, the catechol-mediated cycle should be the principal route of enzymatic degradation of phenol and its oxidation products. This study highlights the potential industrial applications associated with the production of MnP by genetic engineering methods, and the application of industrial wastewater treatment.

Initial Gut Microbial Composition as a Key Factor Driving Host Response to Antibiotic Treatment, as Exemplified by the Presence or Absence of Commensal Escherichia coli.

Antibiotics are important for treating bacterial infection; however, efficacies and side effects of antibiotics vary in medicine and experimental models. A few studies have correlated microbiota composition variations with health outcomes in response to antibiotics; however, no study has demonstrated causality. We had noted variation in colonic expression of C-type lectins, regenerating islet-derived protein 3ß (Reg3ß) and Reg3γ, after metronidazole treatment in a mouse model. To investigate the effects of specific variations in the preexisting microbiome on host response to antibiotics, mice harboring a normal microbiota were allocated to 4 treatments in a 2-by-2 factorial arrangement with or without commensal Escherichia coli and with or without metronidazole in drinking water. E. coli colonized readily without causing a notable shift in the microbiota or host response. Metronidazole administration reduced microbiota biodiversity, indicated by decreased Chao1 and Shannon index values, and altered microbiota composition. However, the presence of E. coli strongly affected metronidazole-induced microbiota shifts. Remarkably, this single commensal bacterium in the context of a complex population led to variations in host responses to metronidazole treatment, including increased expression of antimicrobial peptides Reg3ß and Reg3γ and intestinal inflammation indicated by tumor necrosis factor alpha levels. Similar results were obtained from 2-week antibiotic exposure and with additional E. coli isolates. The results of this proof-of-concept study indicate that even minor variations in initial commensal microbiota can drive shifts in microbial composition and host response after antibiotic administration. As well as providing an explanation for variability in animal models using antibiotics, the findings encourage the development of personalized medication in antibiotic therapies.IMPORTANCE This work provides an understanding of variability in studies where antibiotics are used to alter the gut microbiota to generate a host response. Furthermore, although providing evidence only for the one antibiotic, the study demonstrated that initial gut microbial composition is a key factor driving host response to antibiotic administration, creating a compelling argument for considering personalized medication based on individual variations in gut microbiota.

A longitudinal study on urinary cadmium and renal tubular protein excretion of nickel-cadmium battery workers after cessation of cadmium exposure.

PURPOSE: This study aimed to predict the outcome of urinary cadmium (Cd) excretion and renal tubular function by analyzing their evolution through 10 years after Cd exposure ceased. METHODS: Forty-one female, non-smoking workers were recruited from the year 2004 to 2009 when being removed from a nickel-cadmium battery factory, and they were asked to provide morning urine samples on three consecutive days at enrollment and in every follow-up year until 2014. Urinary Cd and renal tubular function biomarkers including urinary ß2-microglobulin (ß2-m) and retinol-binding protein (RBP) concentrations were determined with the graphite furnace atomic absorption spectrometry and the enzyme-linked immunosorbent assays, respectively. RESULTS: The medians of baseline Cd, ß2-m and RBP concentrations at enrollment were 6.19, 105.38 and 71.84 µg/g creatinine, respectively. Urinary ß2-m and RBP concentrations were both related to Cd concentrations over the years (ß absolute-ß2-m = 9.16, P = 0.008 and ß absolute-RBP = 6.42, P < 0.001, respectively). Cd, ß2-m and RBP concentrations in the follow-up years were all associated with their baseline concentrations (ß absolute-Cd = 0.61, P < 0.001; ß absolute-ß2-m = 0.64, P < 0.001; and ß absolute-RBP = 0.60, P < 0.001, respectively), and showed a decreasing tendency with the number of elapsed years relative to their baseline concentrations (ß relative-Cd = -0.20, P = 0.010; ß relative-ß2-m = -17.19, P = 0.002; and ß relative-RBP = -10.66, P < 0.001, respectively). CONCLUSIONS: Urinary Cd might eventually decrease to the general population level, and Cd-related tubular function would improve under the baseline conditions of this cohort.

Isoflavones extracted from chickpea Cicer arietinum L. sprouts induce mitochondria-dependent apoptosis in human breast cancer cells.

Isoflavones are important chemical components of the seeds and sprouts of chickpeas. We systematically investigated the effects of isoflavones extracted from chickpea sprouts (ICS) on the human breast cancer cell lines SKBr3 and Michigan Cancer Foundation-7 (MCF-7). 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays showed that ICS (10-60 µg/mL) significantly inhibited the proliferation of both cell lines in a time-dependent and dose-dependent fashion. Wright-Giemsa staining as well as annexin V-fluorescein isothiocyanate and propidium iodide (Annexin V/PI) staining showed that ICS significantly increased cytoclasis and apoptotic body formation. Quantitative Annexin V/PI assays further showed that the number of apoptotic cells increased in a dose-dependent manner following ICS treatment. Semiquantitative reverse transcription PCR showed that ICS increased the expression of the apoptosis-promoting gene Bcl-2-associated X protein and decreased the expression of the antiapoptotic gene Bcl-2. Western blot analysis showed that treatment of SKBr3 and MCF-7 cells with ICS increased the expression of caspase 7, caspase 9, P53, and P21 in a dose-dependent manner. Flow cytometry assays using the fluorescent probe 3,3'-dihexyloxacarbocyanine iodide showed a dose-dependent decrease in mitochondrial membrane potential following ICS treatment. Treatment using ICS also induced a dose-dependent increase in reactive oxygen species production. This is the first study to demonstrate that ICS may be a chemopreventive or therapeutic agent against breast cancer.

A scatter correction method for dual-energy digital mammography: Monte Carlo simulation.

PURPOSE: To develop a novel scatter correction method without additional patient dose for dual-energy digital mammography (DEDM) to reduce scatter's impacts and enhance microcalcification detectability in dual-energy X-ray subtraction image. METHODS: Combining scatter radiation is lower spatial frequency component and calcifications are sparsely distributed in digital mammogram, we develop a new scatter correction strategy. First, an adaptive sampling scheme is presented to find possible noncalcification (zero calcification) pixels. Then the maximum likelihood expectation maximization (MLEM) algorithm is applied to evaluate initial scatter surface. The accurate scatter radiation of sampling pixels is obtained by solving dual-energy computational formula with zero calcification constraint and scatter surface constraint. RESULTS: After scatter correction, the scatter-to-primary ratio (SPR) of wedge phantom is reduced from ~36.0% to ~3.1% for low-energy (LE) image and ~29.6% to ~0.6% for high-energy (HE) image. For step phantom, the SPR is reduced from ~42.1% and ~30.3% to ~3.9% and ~0.9% for LE and HE image, respectively. The calcification contrast-to-noise ratio is improved by two orders of magnitudes in calcification images. CONCLUSIONS: The proposed method shows an excellent performance on scatter reduction and calcification detection. Compared with hardware based scatter correction strategy, our method need no extra exposure and is easy to implementation.

[MicroRNA-210 mediates the protective effect of rosuvastatin on human mesenchymal stem cells apoptosis induced by tumor necrosis factor-α].

OBJECTIVE: To explore the effect and mechanism of rosuvastatin on tumor necrosis factor-α induced human mesenchymal stem cells (MSCs) apoptosis. METHOD: Human MSCs were treated as follows: (1) culture medium; (2) TNF-α (20 µg/ml) for 6 h; (3) rosuvastatin (20 µmol/L) for 24 h; (4) rosuvastatin (20 µmol/L) for 24 h followed by TNF-α (20 µg/ml) for 6 h; (5) TNF-α+rosuvastatin+50 nmol/L antago-miRNA; (6) TNF-α+rosuvastatin+100 nmol/L antago-miRNA. Cell survival and apoptosis were determined by MTT, TUNEL and caspase-3 activity assay. The changes of miRNA-210 in each group were detected with quantitative PCR. RESULT: TNF-α significantly induced human MSCs apoptosis in a concentration-dependent manner, and pretreatment with rosuvastatin significantly reduced MSCs apoptosis (caspase-3 assay: TNF-α+Statin group vs. TNF-α group: (1.63 ± 0.25) vs. (2.05 ± 0.36), P < 0.05). Meanwhile, TNF-α progressively reduced the expression of miRNA-210 in human MSCs in a dose-dependent manner, while the miRNA-210 expression was significantly upregulated in TNF-α+Statin group (P < 0.05). The protective effect of rosuvastatin on TNF-α induced MSCs apoptosis was largely abolished by co-treatment with 100 nmol/L antago-miRNA (TUNEL:TNF-α + Statin + antago-miR group vs. TNF-α + Statin group: (42.58 ± 6.71) % vs. (16.87 ± 9.27) %, P < 0.05). CONCLUSION: Pretreatment with rosuvastatin can significantly improve the viability of human MSCs after TNF-α injury, the protective mechanism of rosuvastatin is partly mediated through miRNA-210 up-regulation.

Oncolytic Therapy of Solid Tumors by Modified Vesicular Stomatitis Virus.

Vesicular stomatitis virus (VSV) is a promising oncolytic virus for treating solid tumors. We recently engineered a replicating VSV that specifically targets and destroys Her2/neu-expressing cancer cells. This virus was created by eliminating its natural binding site and adding a coding sequence for a single chain antibody to the Her2/neu receptor into its genome. Such an approach can be tailored to target various cellular surface molecules. This mini review will discuss genomic modifications of VSVs and their role in oncolytic therapy and discuss some challenges for moving VSVs to clinical applications.

Epidemiological characteristics and factors affecting healing in unintentional pediatric wounds.

Objective: To analyze the epidemiological characteristics and wound healing conditions of common unintentional skin lacerations in children. Methods: A retrospective analysis was conducted on data from 1,107 children, aged 0-12 years, with skin lacerations who received emergency treatment at Qilu Hospital of Shandong University from January 1, 2019, to December 30, 2022. Data on age, injury site, time from injury to suturing, and wound healing conditions were statistically analyzed. Results: Among the 1,107 cases, 714 (64.5%) were male and 393 (35.5%) were female, with a male-to-female ratio of 1.8:1; median age was 5 years (IQR, 3-7). Infants and toddlers (0-3 years old) constituted the highest proportion, accounting for 36.3% (402 cases). The number of children aged over 3 years gradually decreased with increasing age. In younger children, the most common injuries were to the forehead, scalp, and lower jaw; in school-aged children, the proportion of limb and trunk injuries significantly increased. Age (OR, 1.34; 95% CI, 1.23-1.46), outdoor injuries (OR, 2.21; 95% CI, 1.18-4.16), lower limb injuries (OR, 5.35; 95% CI, 2.86-10.00), and wound length greater than 3 cm (OR, 10.65; 95% CI, 5.02-22.60) were significant risk factors for poor wound healing. The risk of poor wound healing increased by 34% for each additional year of age. Conclusion: In children, the common sites of unintentional skin lacerations show distinct age and gender distribution characteristics. Older age, outdoor injuries, longer wound lengths, and lower limb injuries are independent risk factors for poor wound healing.

Isoflavones isolated from chickpea sprouts alleviate ovariectomy-induced osteoporosis in rats by dual regulation of bone remodeling.

Osteoporosis is a common systemic skeletal disease and a predominant underlying factor in the increased occurrence of fractures. The structure of isoflavones resembles that of estrogen and can confer similar but weaker effects. This study investigated the potential inhibitory effects of isoflavones from chickpea sprouts (ICS) on ovariectomy (OVX)-induced osteoporosis in vitro and in vivo. Notably, we found that ICS treatment could attenuate bone loss and improve trabecular microarchitecture and biomechanical properties of the fourth lumbar vertebra in OVX-induced osteoporotic rats and could also inhibit the development of a hyperosteometabolic state in this model. The osteogenic differentiation of bone marrow stem cells (BMSCs) was significantly enhanced by ICS intervention in vitro, and we confirmed that estrogen receptor α signaling was required for this increased osteogenic differentiation. Additionally, ICS has been shown to inhibit bone resorption via ERa modulation of the OPG/RANKL pathway. RANKL-induced osteoclastogenesis was reduced under ICS treatment, supporting that NF-κB signaling was inhibited by ICS. Thus, ICS attenuates osteoporosis progression by promoting osteogenic differentiation and inhibiting osteoclastic resorption. These results support the further exploration and development of ICS as a pharmacological agent for the treatment and prevention of osteoporosis.

Meta-analysis of randomized controlled trials on magnesium in addition to beta-blocker for prevention of postoperative atrial arrhythmias after coronary artery bypass grafting.

BACKGROUND: Atrial arrhythmia (AA) is the most common complication after coronary artery bypass grafting (CABG). Only beta-blockers and amiodarone have been convincingly shown to decrease its incidence. The effectiveness of magnesium on this complication is still controversial. This meta-analysis was performed to evaluate the effect of magnesium as a sole or adjuvant agent in addition to beta-blocker on suppressing postoperative AA after CABG. METHODS: We searched the PubMed, Medline, ISI Web of Knowledge, Cochrane library databases and online clinical trial database up to May 2012. We used random effects model when there was significant heterogeneity between trials and fixed effects model when heterogeneity was negligible. RESULTS: Five randomized controlled trials were identified, enrolling a total of 1251 patients. The combination of magnesium and beta-blocker did not significantly decrease the incidence of postoperative AA after CABG versus beta-blocker alone (odds ratio (OR) 1.12, 95% confidence interval (CI) 0.86-1.47, P = 0.40). Magnesium in addition to beta-blocker did not significantly affect LOS (weighted mean difference -0.14 days of stay, 95% CI -0.58 to 0.29, P = 0.24) or the overall mortality (OR 0.59, 95% CI 0.08-4.56, P = 0.62). However the risk of postoperative adverse events was higher in the combination of magnesium and beta-blocker group than beta-blocker alone (OR 2.80, 95% CI 1.66-4.71, P = 0.0001). CONCLUSIONS: This meta-analysis offers the more definitive evidence against the prophylactic administration of intravenous magnesium for prevention of AA after CABG when beta-blockers are routinely administered, and shows an association with more adverse events in those people who received magnesium.

Assessment of the estrogenic activities of chickpea (Cicer arietinum L) sprout isoflavone extract in ovariectomized rats.

AIM: Chickpea (Cicer arietinum L) is a traditional Uighur herb. In this study we investigated the estrogenic activities of the isoflavones extracted from chickpea sprouts (ICS) in ovariectomized rats. METHODS: Ten-week-old virgin Sprague-Dawley female rats were ovariectomized (OVX). The rats were administered via intragastric gavage 3 different doses of ICS (20, 50, or 100 mg·kg(-1)·d(-1)) for 5 weeks. Their uterine weight and serum levels of 17ß-estradiol (E2), follicle stimulating hormone (FSH) and luteinizing hormone (LH) were measured. The epithelial height, number of glands in the uterus, and number of osteoclasts in the femur were histologically quantified, and the expression of proliferating cell nuclear antigen (PCNA) was assessed immunohistochemically. Bone structural parameters, including bone mineral density (BMD), bone volume/tissue volume (BV/TV), trabecular thickness (Tb.Th) and trabecular separation (Tb.Sp) were measured using Micro-CT scanning. RESULTS: Treatments of OVX rats with ICS (50 or 100 mg·kg(-1)·d(-1)) produced significant estrogenic effects on the uteruses, including the increases in uterine weight, epithelial height and gland number, as well as in the expression of the cell proliferation marker PCNA. The treatments changed the secretory profile of ovarian hormones and pituitary gonadotropins: serum E2 level was significantly increased, while serum LH and FSH levels were decreased compared with the vehicle-treated OVX rats. Furthermore, the treatments significantly attenuated the bone loss, increased BMD, BV/TV and Tb.Th and decreased Tb.Sp and the number of osteoclasts. Treatment of OVX rats with the positive control drug E2 (0.25 mg·kg(-1)·d(-1)) produced similar, but more prominent effects. CONCLUSION: ICS exhibits moderate estrogenic activities as compared to E2 in ovariectomized rats, suggesting the potential use of ICS for the treatment of menopausal symptoms and osteoporosis caused by estrogen deficiency.

Anti-tumor memory CD4 and CD8 T-cells quantified by bulk T-cell receptor (TCR) clonal analysis.

Simple, reliable methods to detect anti-tumor memory T-cells are necessary to develop a clinical tumor vaccination program. A mouse model of curative viral onco-immunotherapy found that peritoneal tumor challenge following cure identified an oligoclonal anti-tumor memory CD4 and CD8 T-cell response. Clonotypes differed among the challenged animals but were congruent in blood, spleen and peritoneal cells (PC) of the same animal. Adoptive transfer demonstrated that the high-frequency responding T-cells were tumor specific. Tetramer analysis confirmed that clonotype frequency determined by T-cell receptor (TCR)- chain (TRB) analysis closely approximated cell clone frequency. The mean frequency of resting anti-tumor memory CD4 T-cells in unchallenged spleen was 0.028% and of memory CD8 T-cells was 0.11% which was not high enough to distinguish them from background. Stimulation produced a mean ~10-fold increase in splenic and 100-fold increase in peritoneal anti-tumor memory T-cell clonotypes. This methodology can be developed to use blood and tissue sampling to rapidly quantify the effectiveness of a tumor vaccine or any vaccine generating therapeutic T-cells.