The Helicobacter pylori CagY Protein Drives Gastric Th1 and Th17 Inflammation and B Cell Proliferation in Gastric MALT Lymphoma

Background: the neoplastic B cells of the Helicobacter pylori-related low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma proliferate in response to H. pylori, however, the nature of the H. pylori antigen responsible for proliferation is still unknown. The purpose of the study was to dissect whether CagY might be the H. pylori antigen able to drive B cell proliferation. Methods: the B cells and the clonal progeny of T cells from the gastric mucosa of five patients with MALT lymphoma were compared with those of T cell clones obtained from five H. pylori–infected patients with chronic gastritis. The T cell clones were assessed for their specificity to H. pylori CagY, cytokine profile and helper function for B cell proliferation. Results: 22 of 158 CD4⁺ (13.9%) gastric clones from MALT lymphoma and three of 179 CD4⁺ (1.7%) clones from chronic gastritis recognized CagY. CagY predominantly drives Interferon-gamma (IFN-γ) and Interleukin-17 (IL-17) secretion by gastric CD4⁺ T cells from H. pylori-infected patients with low-grade gastric MALT lymphoma. All MALT lymphoma-derived clones dose dependently increased their B cell help, whereas clones from chronic gastritis lost helper activity at T-to-B-cell ratios greater than 1. Conclusion: the results obtained indicate that CagY drives both B cell proliferation and T cell activation in gastric MALT lymphomas.     

Cachexia as Evidence of the Mechanisms of Resistance and Tolerance during the Evolution of Cancer Disease

During its evolution, cancer induces changes in patients’ energy metabolism that strongly affect the overall clinical state and are responsible for cancer-related cachexia syndrome. To better understand the mechanisms underlying cachexia and its metabolic derangements, research efforts should focus on the events that are driven by the immune system activation during the evolution of neoplastic disease and on the phenomena of “resistance” and “tolerance” typically involved in the human body response against stress, pathogens, or cancer. Indeed, in the case where resistance is not able to eliminate the cancer, tolerance mechanisms can utilize the symptoms of cachexia (anemia, anorexia, and fatigue) to counteract unregulated cancer growth. These notions are also sustained by the evidence that cancer cachexia may be reversible if the resistance and tolerance phases are supported by appropriate antineoplastic treatments. Accordingly, there is no doubt that anticachectic therapies have an irreplaceable role in cases of reversible cancer cachexia where, if harmoniously associated with effective antineoplastic therapies, they can contribute to preserve the quality of life and improve prognosis. Such anticachectic treatments should be based on targeting the complex immunological, inflammatory, and metabolic pathways involved in the complex pathogenesis of cachexia. Meanwhile, the role of the anticachectic therapies is very different in the stage of irreversible cachexia when the available antineoplastic treatments are not able to control the disease and the resistance mechanisms fail with the prevalence of the tolerance phenomena. At this stage, they can be useful only to improve the quality of life, allowing the patient and their family to get a better awareness of the final phases of life, thereby opening to the best spiritual remodulation of the final event, death.     

Effects of inulin,fructooligosaccharides/glucose and pH on the shape of the death kinetic of Lactobacillus reuteri DSM 20016

The viability of Lactobacillus reuteri, Lb. delbrueckii subsp. bulgaricus and Lb. paracasei was assessed in a laboratory medium containing inulin (5 g L^?1) or glucose + FOS (fructooligosaccharides) (2.5 + 2.5 g L^?1). Data were modelled through the Weibull equation pinpointing that prebiotics determined a decrease in the shape parameter. In the 2nd step, L. reuteri was used as the test microorganism; pH, storage temperature and the amounts of FOS + glucose and inulin were combined through a 4‐variable/5‐level central composite design. Temperature, pH and glucose + FOS affected the microbiological shelf life; inulin was not significant. The maximum value of shelf life was found at pH 8.5 and with 5.0 g L^?1 of glucose + FOS. The combination of pH and prebiotics affected the shape parameter with a shift from a convex to a concave trend and vice versa: their effect was different depending on the use of a single prebiotic or a mix.     

On the regularity of circular splicing languages: a survey and new developments

Circular splicing has been introduced to model a specific recombinant behaviour of circular DNA, continuing the investigation initiated with linear splicing. In this paper we focus on the relationship between regular circular languages and languages generated by finite circular splicing systems. We survey the known results towards a characterization of the intersection between these two classes and provide new contributions on the open problem of finding this characterization. First, we exhibit a non-regular circular language generated by a circular simple system thus disproving a known result in this area. Then we give new results related to a restrictive class of circular splicing systems, the marked systems. Precisely, we review in a graph theoretical setting the recently obtained characterization of marked systems generating regular circular languages. In particular, we define a slight variant of marked systems, that is the g-marked systems, and we introduce the graph associated with a g-marked system. We show that a g-marked system generates a regular circular language if and only if its associated graph is a cograph. Furthermore, we prove that the class of g-marked systems generating regular circular languages is closed under a complement operation applied to systems. We also prove that marked systems with self-splicing generate only regular circular languages.     

Kaposi’s Sarcoma Lesion Progression in BKV-Tat Transgenic Mice Is Increased by Inflammatory Cytokines and Blocked by Treatment with Anti-Tat Antibodies

Kaposi’s sarcoma (KS) is an angioproliferative tumor showing an increased frequency and aggressiveness in HIV-infected subjects (AIDS-KS), due to the combined effects of inflammatory cytokines (IC), angiogenic factors, and the HIV-1 Tat protein. While the introduction of effective combined antiretroviral regimens greatly improved AIDS-KS incidence and course, it continues to be an incurable disease and the development of new rational targeted therapies is warranted. We used the BKV/Tat transgenic mouse model to evaluate the effects of IC and anti-Tat antibodies (Abs) treatment on KS-like lesions arising in BKV/Tat mice. We demonstrated here that IC-treatment increases the severity and delays the regression of KS-like lesions. Further, anti-Tat Abs reduced KS-like lesion severity developing in IC-treated mice when anti-Tat Abs were administered at an early-stage of lesion development as compared to more advanced lesions. Early anti-Tat Abs treatment also accelerated KS-like lesion regression and reduced the rate of severe-grade lesions. This effect was more evident in the first weeks after Ab treatment, suggesting that a longer treatment with anti-Tat Abs might be even more effective, particularly if administered just after lesion development. Although preliminary, these results are encouraging, and the approach deserves further studies for the development of anti-Tat Ab-based therapies for AIDS-KS. Clinical studies specifically addressing the effect of anti-Tat antibodies in treating AIDS-KS are not yet available. Nevertheless, the effectiveness of anti-Tat antibodies in controlling HIV/AIDS progression, likely due to the neutralization of extracellular Tat activities, is suggested by several cross-sectional and longitudinal clinical studies, indicating that anti-Tat Ab treatment or Tat-based vaccines may be effective to treat AIDS-KS patients or prevent the tumor in individuals at risk.     

Inhibition of Aspergillus spp. and Penicillium spp. by fatty acids and their monoglycerides

The antifungal activity of three fatty acids (lauric, myristic, and palmitic acids) and their monoglycerides (monolaurin, monomyristic acid, and palmitin, respectively) against Aspergillus and Penicillium species in a model system was investigated. Data were modeled through a reparameterized Gompertz equation. The maximum colony diameter attained within the experimental time (30 days), the maximal radial growth rate, the lag time (i.e., the number of days before the beginning of radial fungal growth), and the minimum detection time (MDT; the number of days needed to attain 1 cm colony diameter) were evaluated. Fatty acids and their monoglycerides inhibited mold growth by increasing MDT and lag times. The effectiveness of the active compounds seemed to be strain and genus dependent. Palmitic acid was the most effective chemical against aspergilli, whereas penicilli were strongly inhibited by myristic acid. Aspergilli also were more susceptible to fatty acids than were penicilli, as indicated by the longer MDT.     

Dietary Supplementation with the Probiotic SF68 Reinforces Intestinal Epithelial Barrier in Obese Mice by Improving Butyrate Bioavailability

Scope

Modifications in intestinal microbiota and its metabolites, the short-chain fatty acids (SCFA) are main factors altering intestinal epithelial barrier integrity and eliciting the onset of a meta-inflammation observed in obesity. The present study is aimed at evaluating the efficacy of Enterococcus faecium (SF68) administration in counteracting the impairment of gut barrier and enteric inflammation in a model of diet-induced obesity, characterizing the molecular mechanisms underlying such beneficial effects.

Methods and Results

Male C57BL/6J mice, fed with standard diet (SD) or high-fat diet (HFD), are treated with SF68 (10⁸ CFU day⁻¹). After 8 weeks, plasma interleukin (IL)-1β and lipopolysaccharide binding protein (LBP) are measured, analysis of fecal microbiota composition and butyrate content as well as intestinal malondialdehyde, myeloperoxidase, mucins, tight junction protein, and butyrate transporter expression are investigated. After 8 weeks, SF68 administration counteracts the body weight gain in HFD mice, reducing plasma IL-1β and LBP. In parallel, SF68 treatment acts against the intestinal inflammation in HFD-fed animals and improves the intestinal barrier integrity and functionality in obese mice via the increase in tight junction protein and intestinal butyrate transporter (sodium-coupled monocarboxylate transporter 1 ) expression.

Conclusions

Supplementation with SF68 reduces intestinal inflammation and reinforces the enteric epithelial barrier in obese mice, improving the transport and utilization of butyrate.     

Synthesis,characterisation and properties of α,β-poly(N-2-hydroxyethyl)-dl-aspartamide-graft-maleic anhydride precursors and their stimuli-responsive hydrogels

A family of poly(amino acid)-maleic anhydride hydrogels were designed and synthesized. Water soluble polymeric precursors were prepared by partially substituting the hydroxyl groups of the α,β-poly(N-2-hydroxyethyl)-dl-aspartamide backbone with maleic anhydride, so as to provide double bonds for crosslinking and carboxylic acid groups for pH and electric field responsiveness. Reaction conditions (reactive mixture composition and catalysis) were systematically varied in order to obtain PHEA–MA precursors with different and reliable graft-maleic anhydride levels. PHEA–MA precursors were characterised by titration, Nuclear Magnetic Resonance (¹H NMR), Fourier-Transformed Infrared Spectroscopy (FTIR) and Size Exclusion Chromatography (SEC) for structural and molecular determination. Aqueous solutions of selected PHEA–MA precursors were subjected to gamma-irradiation at different irradiation doses and polymer to water concentrations in order to induce chemical crosslinking without the addition of crosslinking agents. The yield of crosslinking reactions was evaluated by solubility tests as well as the effect of ammonium persulphate, as assistant radical initiator for gamma crosslinking. Selected hydrogels were tested through swelling measurements to prove their pH and electric field responsiveness. Structural features of the different variants produced were related to the swelling behaviour.