6-Shogaol attenuated ethylene glycol and aluminium chloride induced urolithiasis and renal injuries in rodents

The 6-shogaol, is a flavanone type flavonoid that is abundant in citrus fruit and has a wide range of pharmacological effects. The present study attempted to evaluate the antiurolithic effect of 6-shogaol on ethylene glycol (EG) and ammonium chloride (AC)-induced experimental urolithiasis in rats. The efficacy of 6-shogaol 50 mg/kg and 100 mg/kg was studied in EG 0.75% (V/V) and AC 1% (W/V) experimentally induced urolithiasis in rats for 21 days. The weight difference, urine volume, the levels of calcium, phosphate, magnesium, oxalate and uric acid in urine was observed. The blood urea nitrogen, creatinine, uric acid in serum and levels of malondialdehyde (MDA) and glutathione (GSH) were also measured. Histopathological analyses in kidneys were also performed. The rats weights were higher in the 6-shogaol groups than the urolithiasis group. EG caused a significant increase in serum creatinine (p < 0.05), BUN (P < 0.001), and uric acid (p < 0.01) while treatment with Cystone (750 mg/kg), and 6-shogaol (50 and 100 mg/kg) showed the significant reduction in increased serum levels of creatinine (p < 0.001), uric acid (p < 0.01) and BUN (p < 0.001). Administration of EG and AC showed statistically significant (p < 0.001) elevated levels of MDA and reduction in GSH levels. Treatment of Cystone (750 mg/kg), and 6-shogaol (50 and 100 mg/kg) significantly (p < 0.001) reduced MDA levels and an increase GSH levels as compared to EG and AC-treated group. The histological findings further attested antiurolithiatic properties of 6-shogaol. The present study attributed clinical shreds of evidence first time that claiming the significant antiurolithic effect of 6-shogaol and could be a cost-effective candidate for the prevention and treatment of urolithiasis.     

CD8 alpha beta T cells are not essential to the pathogenesis of arthritis or colitis in HLA-B27 transgenic rats

The class I MHC allele HLA-B27 is highly associated with the human spondyloarthropathies, but the basis for this association remains poorly understood. Transgenic rats with high expression of HLA-B27 develop a multisystem inflammatory disease that includes arthritis and colitis. To investigate whether CD8alphabeta T cells are needed in this disease, we depleted these cells in B27 transgenic rats before the onset of disease by adult thymectomy plus short-term anti-CD8alpha mAb treatment. This treatment induced profound, sustained depletion of CD8alphabeta T cells, but failed to suppress either colitis or arthritis. To address the role of CD8alpha(+)beta(-) cells, we studied four additional groups of B27 transgenic rats treated with: 1) continuous anti-CD8alpha mAb, 2) continuous isotype-matched control mAb, 3) the thymectomy/pulse anti-CD8alpha regimen, or 4) no treatment. Arthritis occurred in approximately 40% of each group, but was most significantly reduced in severity in the anti-CD8alpha-treated group. In addition to CD8alphabeta T cells, two sizeable CD8alpha(+)beta(-) non-T cell populations were also reduced by the anti-CD8alpha treatment: 1) NK cells, and 2) a CD4(+)CD8(+)CD11b/c(+)CD161a(+)CD172a(+) monocyte population that became expanded in diseased B27 transgenic rats. These data indicate that HLA-B27-retricted CD8(+) T cells are unlikely to serve as effector cells in the transgenic rat model of HLA-B27-associated disease, in opposition to a commonly invoked hypothesis concerning the role of B27 in the spondyloarthropathies. The data also suggest that one or more populations of CD8alpha(+)beta(-) non-T cells may play a role in the arthritis that occurs in these rats.     

Ant community composition and functional traits in new grassland strips within agricultural landscapes

1. Ongoing intensification and fragmentation of European agricultural landscapes dramatically reduce biodiversity and associated functions. Enhancing perennial noncrop areas holds great potential to support ecosystem services such as ant‐mediated pest control.
2. To study the potential of newly established grassland strips to enhance ant diversity and associated functions, we used hand collection data and predation experiments to investigate differences in (a) ant community composition and (b) biocontrol‐related functional traits, and (c) natural pest control across habitats in cereal fields, old grasslands, and new grassland transects of three years of age.
3. Ant species diversity was similar between new and old grasslands, but significantly higher in new grasslands than in surrounding cereal fields. Contrary, ant community composition of new grasslands was more similar to cereal fields and distinct from the species pool of old grasslands. The functional trait space covered by the ant communities showed the same distribution between old and new grasslands. Pest control did not differ significantly between habitat types and therefore could not be linked to the prevalence of functional ant traits related to biocontrol services in new grasslands.
4. Our findings not only show trends of convergence between old and new grasslands, but also indicate that enhancing ant diversity through new grasslands takes longer than three years to provide comparable biodiversity and functionality.
5. Synthesis and applications: Newly established grasslands can increase ant species richness and abundance and provide a consistent amount of biocontrol services in agroecosystems. However, three years after their establishment, new grasslands were still dominated by common agrobiont ant species and lacked habitat specialists present in old grasslands, which require a constant supply of food resources and long colony establishment times. New grasslands represent a promising measure for enhancing agricultural landscapes but must be preserved in the longer term to promote biodiversity and resilience of associated ecosystem services.

     

PuraMatrix Encapsulation of Cancer Cells

Increasing evidence suggests that culturing cancer cells in three dimensions more accurately recapitulates the complexity of tumor biology. Many of these models utilize reconstituted basement membrane derived from animals which contain a variable amount of growth factors and cytokines that can influence the growth of these cell culture models. Here, we describe in detail the preparation and use of PuraMatrix, a commercially available self assembling peptide gel that is devoid of animal-derived material and pathogens to encapsulate and propagate the ovarian cancer cell line, OVCAR-5. We begin by describing how to prepare the PuraMatrix prior to use. Next, we demonstrate how to properly mix the PuraMatrix and cell suspension to encapsulate the cells in the hydrogel. Upon the addition of cell culture media or injection into a physiological environment, the peptide component of PuraMatrix rapidly self assembles into a 3D hydrogel that exhibits a nanometer scale fibrous structure with an average pore size of 5-200 nm¹. In addition, we demonstrate how to propagate cultures grown in encapsulated PuraMatrix. When encapsulated in PuraMatrix, OVCAR-5 cells assemble into three dimensional acinar structures that more closely resemble the morphology of micrometastatic nodules observed in the clinic than monolayer in vitro models. Using confocal microscopy we illustrate the appearance of representative OVCAR-5 cells encapsulated in PuraMatrix on day 1, 3, 5, and 7 post plating. The use of PuraMatrix to culture cancer cells should improve our understanding of the disease and allow us to assess treatment response in more clinically predictive model systems.Download video file.^{(85M, mp4)}     

Mycobacterium tuberculosis secretory proteins CFP-10, ESAT-6 and the CFP10:ESAT6 complex inhibit lipopolysaccharide-induced NF-kappaB transactivation by downregulation of reactive oxidative species (ROS) production

Mycobacterium tuberculosis (Mtb) causes death of 2-3 million people annually and is considered one of the most successful intracellular pathogens to persist inside the host macrophage. Recent studies have implicated the role of RD-1 region of Mtb genome in the mycobacterial pathogenesis. The role of RD-1-encoded secretory proteins of Mtb in modulation of macrophage function has not been investigated in detail. Here we show that RD-1 encoded two major secretory proteins, namely, culture filtrate protein-10 kDa (CFP-10) and early secreted antigenic target-6 kDa (ESAT-6), and their 1:1 CFP-10:ESAT6 complex inhibit production of reactive oxidative species (ROS) in RAW264.7 cells. These proteins also downregulated the bacterial lipopolysaccharide (LPS)-induced ROS production, which, in turn, downregulated LPS-induced nuclear factor-kappaB (NF-kappaB) p65 DNA-binding activity, as well as inhibited the NF-kappaB-dependent reporter gene (chloramphenicol acetyl transferase) expression in the treated macrophages. Moreover, addition of N-acetyl cysteine, which is a scavenger of ROS, also inhibited LPS-induced reporter gene expression by scavenging the ROS, thereby preventing NF-kappaB transactivation. These studies indicate that the secretory proteins CFP-10, ESAT-6 and the CFP10:ESAT6 complex of Mtb can inhibit LPS-induced NF-kappaB-dependent gene expression via downregulation of ROS production.     

HIF-1α Plays a Critical Role in the Gestational Sidestream Smoke-Induced Bronchopulmonary Dysplasia in Mice

Rationale

Smoking during pregnancy increases the risk of bronchopulmonary dysplasia (BPD) and, in mice, gestational exposure to sidestream cigarette smoke (SS) induces BPD-like condition characterized by alveolar simplification, impaired angiogenesis, and suppressed surfactant protein production. Normal fetal development occurs in a hypoxic environment and nicotinic acetylcholine receptors (nAChRs) regulate the hypoxia-inducible factor (HIF)-1α that controls apoptosis and angiogenesis. To understand SS-induced BPD, we hypothesized that gestational SS affected alveolar development through HIF-1α.

Methods

Pregnant BALB/c mice were exposed to air (control) or SS throughout the gestational period and the 7-day-old lungs of the progeny were examined.

Results

Gestational SS increased apoptosis of alveolar and airway epithelial cells. This response was associated with increased alveolar volumes, higher levels of proapoptotic factors (FOXO3a, HIPK2, p53, BIM, BIK, and BAX) and the antiangiogenic factor (GAX), and lower levels of antiapoptotic factors (Akt-PI3K, NF-κB, HIF-1α, and Bcl-2) in the lung. Although gestational SS increased the cells containing the proangiogenic bombesin-like-peptide, it markedly decreased the expression of its receptor GRPR in the lung. The effects of SS on apoptosis were attenuated by the nAChR antagonist mecamylamine.

Conclusions

Gestational SS-induced BPD is potentially regulated by nAChRs and associated with downregulation of HIF-1α, increased apoptosis of epithelial cells, and increased alveolar volumes. Thus, in mice, exposure to sidestream tobacco smoke during pregnancy promotes BPD-like condition that is potentially mediated through the nAChR/HIF-1α pathway.     

A framework integrating physiology,dispersal and land‐use to project species ranges under climate change

To study the potential effects of climate change on species, one of the most popular approaches are species distribution models (SDMs). However, they usually fail to consider important species‐specific biological traits, such as species’ physiological capacities or dispersal ability. Furthermore, there is consensus that climate change does not influence species distributions in isolation, but together with other anthropogenic impacts such as land‐use change, even though studies investigating the relative impacts of different threats on species and their geographic ranges are still rare. Here we propose a novel integrative approach which produces refined future range projections by combining SDMs based on distribution, climate, and physiological tolerance data with empirical data on dispersal ability as well as current and future land‐use. Range projections based on different combinations of these factors show strong variation in projected range size for our study species Emberiza hortulana. Using climate and physiological data alone, strong range gains are projected. However, when we account for land‐use change and dispersal ability, future range‐gain may even turn into a future range loss. Our study highlights the importance of accounting for biological traits and processes in species distribution models and of considering the additive effects of climate and land‐use change to achieve more reliable range projections. Furthermore, with our approach we present a new tool to assess species’ vulnerability to climate change which can be easily applied to multiple species.