Therapeutic effectiveness of orally administered transgenic low-alkaloid tobacco expressing human interleukin-10 in a mouse model of colitis

Inflammatory bowel disease (IBD) represents a spectrum of diseases in which inflammation leads to acute and chronic gut injury. It is a growing health issue for which no cure exists. The pathogenesis is multifactorial with links to infectious and environmental events that trigger disease in genetically predisposed individuals. Treatment of the two major forms of IBD, Crohn's disease and ulcerative colitis, involves the reduction of inflammation with toxic immunosuppressive drugs or blocking of the pro-inflammatory effects of tumour necrosis factor-α (TNF-α) with antibodies. Here, we show that the oral administration of transgenic low-alkaloid tobacco expressing the contra-inflammatory cytokine human interleukin-10 (hIL-10) reduces the severity of colitis by down-regulating TNF-α expression directly at the sites of inflammation in IBD-susceptible IL-10^−/– mice. hIL-10 expressed in plants is biologically active and displays resistance to gastrointestinal degradation. Dietary supplementation with plant tissue delivering up to 9 µg of hIL-10 daily for 4 weeks was well tolerated by treated mice. Gut histology was significantly improved relative to controls ( P =  0.002), and was correlated with a decrease in small bowel TNF-α mRNA levels and an increase in IL-2 and IL-1β mRNA levels. Transgenic plants expressing IL-10 to directly attenuate TNF-α expression at sites of inflammation in the gut may become a useful new approach in the luminal therapy of IBD.     

Testing for homogeneity of gametic disequilibrium across strata

Background

Variance component (VC) models are commonly used for Quantitative Trait Loci (QTL) mapping in outbred populations. Here, the QTL effect is given as a random effect and a critical part of the model is the relationship between the phenotypic values and the random effect. In the traditional VC model, each individual has a unique QTL effect and the relationship between these random effects is given as a covariance structure (known as the identity-by-descent (IBD) matrix).

Results

We present an alternative notation of the variance component model, where the elements of the random effect are independent base generation allele effects and sampling term effects. The relationship between the phenotypic vales and the random effect is given by an incidence matrix, which results in a novel, but statistically equivalent, version of the traditional VC model. A general algorithm to estimate this incidence matrix is presented. Since the model is given in terms of base generation allele effects and sampling term effects, these effects can be estimated separately using best linear unbiased prediction (BLUP). From simulated data, we showed that biallelic QTL effects could be accurately clustered using the BLUP obtained from our model notation when markers are fully informative, and that the accuracy increased with the size of the QTL effect. We also developed a measure indicating whether a base generation marker homozygote is a QTL heterozygote or not, by comparing the variances of the sampling term BLUP and the base generation allele BLUP. A ratio greater than one gives strong support for a QTL heterozygote.

Conclusion

We developed a simple presentation of the VC QTL model for identification of base generation allele effects in QTL linkage analysis. The base generation allele effects and sampling term effects were separated in our model notation. This clarifies the assumptions of the model and should also enhance the development of genome scan methods.     

'Sensing' autoimmunity in type 1 diabetes

Type 1 diabetes (T1D) results from autoimmune-mediated loss of insulin-producing beta-cells. Recent findings suggest that the events controlling T1D development are not only immunological, but also neuronal in nature. In the non-obese diabetic (NOD) mouse model of T1D, a mutant sensory neuron channel, TRPV1, initiates chronic, progressive beta-cell stress, inducing islet cell inflammation. This novel mechanism of organ-specific damage requires a permissive, autoimmune-prone host, but ascribes tissue specificity to the local secretory dysfunction of sensory afferent neurons. In NOD mice, normalizing this neuronal function by administration of the neurotransmitter substance P clears islet cell inflammation, reduces insulin resistance and restores normoglycemia. Here, we discuss this neuro-immuno-endocrine model, its implications and the involvement of sensory neurons in other autoimmune disorders. These developments might provide novel neuronal-based therapeutic interventions, particularly in diabetes.     

Bioaccumulation and ROS generation in liver of Carassius auratus, exposed to phenanthrene

In the present study, the bioaccumulation and reactive oxygen species (ROS) generation were studied after fish (Carassius auratus) were exposed to different concentrations (0.01, 0.02, 0.05, 0.07 and 0.1 mg/L) of phenanthrene for 4 days. The accumulation of phenanthrene in liver increased with the exposure concentration (R(2)=0.88). A secondary spin trapping technique was used followed by electron paramagnetic resonance (EPR) analysis, to study the ROS production. The ROS generated in fish liver after exposure to phenanthrene was identified as hydroxyl radical ((*)OH). The (*)OH signal intensity of the EPR spectrum showed a significant increase (p<0.05) compared to the control when the phenanthrene concentration was as low as 0.05 mg/L. A good positive relationship (R(2)=0.97) was found between the (*)OH formation and exposure concentrations. The changes of the activities of catalase (CAT), superoxide dismutase (SOD), glutathione-S-transferase (GST), and contents of reduced glutathione (GSH) also were detected. The results clearly indicated that phenanthrene could induce (*)OH generation and result in oxidative stress in liver of fish.     

Synthesis of alginic acid-poly[2-(diethylamino)ethyl methacrylate] monodispersed nanoparticles by a polymer-monomer pair reaction system

In this paper, alginic acid-poly(2-(diethylamino)ethyl methacrylate) (ALG-PDEA) nanoparticles were successfully prepared in aqueous medium using a polymer-monomer pair reaction system consisting of the anionic alginic acid (ALG) and the cationic 2-(diethylamino)ethyl methacrylate (DEA), without any aid of surfactants or organic solvents. The ALG-PDEA nanoparticles were monodispersed and stable in aqueous solution. Nanoparticles with desired size could be obtained by varying the amount of initiator or changing the concentration of reactants in solution, which renders this system highly controllable. After the ALG moiety was gelled by Ca(2+), the stability of the nanoparticles in basic or high salt concentration solutions could be notably enhanced. A pH-sensitive anticancer agent, hydroxycamptothecin (HCPT), was encapsulated in ALG-PDEA nanoparticles, and preliminary in vitro release as well as cytotoxicity experiments were carried out. It is found that this system seems to be a very promising carrier for the loading and delivery of labile drugs, taking into account that the preparation procedure is simple, mild, and organic solvent- and surfactant-free. Moreover, the abundant functional groups on the particle surface, such as carboxyls and hydroxyls, allow subsequent chemical modification, which may further unleash the potential of such a system in either biomedical applications or in the construction of other functional mesoscopic architectures.     

Kangiella shandongensis sp. nov., a novel species isolated from saltern in Yantai,China

A Gram-stain-negative, wheat, rod-shaped, non-motile, non-spore forming, and facultatively anaerobic bacterium strain, designated as PI^T, was isolated from saline silt samples collected in saltern in Yantai, Shandong, China. Growth was observed within the ranges 4–45 °C (optimally at 33 °C), pH 6.0–9.0 (optimally at pH 7.0) and 1.0–11.0% NaCl (optimally at 3.0%, w/v). Strain PI^T showed highest 16S rRNA gene sequence similarity to Kangiella sediminilitoris BB-Mw22^T (98.3%) and Kangiella taiwanensis KT1^T (98.3%). The major cellular fatty acids (>?10% of the total fatty acids) were iso-C_15:0 (52.7%) and summed featured 9 (iso-C_17:1ω9c/C_16:0 10-methyl, 11.8%). The major polar lipids identified were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylmonomethylethanolamine and phosphatidylglycerol. The major respiratory isoprenoid quinone was Q-8. The G?+?C content of the genomic DNA was 45.8%. Average Nucleotide Identity values between whole genome sequences of strain PI^T and next related type strains supported the novel species status. Based on physiological, biochemical, chemotaxonomic characteristics and genomic analysis, strain PI^T is considered to represent a novel species within the genus Kangiella, for which the name Kangiella shandongensis sp. nov. is proposed. The type strain is PI^T (=?KCTC 82509 ^T?=?MCCC 1K04352^T).

     

Correction to: Novel biphenyl diester derivative AB-38b inhibits NLRP3 inflammasome through Nrf2 activation in diabetic nephropathy

Cell Biology and Toxicology -     

Rapid detection of Chattonella marina by PCR combined with dot lateral flow strip

Journal of Applied Phycology - In this study a novel technique referred to as PCR combined with dot lateral flow strip (PCDS) is proposed and its application to the detection of harmful microalgae...     

The Effect of α7nAChR Signaling on T Cells and Macrophages and Their Clinical Implication in the Treatment of Rheumatic Diseases

Neurochemical Research - Rheumatoid arthritis (RA) is one of the most common autoimmune disease and until now, the etiology and pathogenesis of RA is not fully understood, although dysregulation of...     

Electro-Acupuncture Pretreatment Ameliorates Anesthesia and Surgery-Induced Cognitive Dysfunction Via Inhibiting Mitochondrial Injury and nEuroapoptosis in Aged Rats

Neurochemical Research - Postoperative cognitive dysfunction (POCD) remains one of the most common complications following anesthesia and surgery (AS) in the elderly population. Calcium-mediated...