A Novel Germline Mutation of ADA2 Gene in Two “Discordant” Homozygous Female Twins Affected by Adenosine Deaminase 2 Deficiency: Description of the Bone-Related Phenotype

Adenosine Deaminase 2 Deficiency (DADA2) syndrome is a rare monogenic disorder prevalently linked to recessive inherited loss of function mutations in the ADA2/CECR1 gene. It consists of an immune systemic disease including autoinflammatory vasculopathies, with a frequent onset at infancy/early childhood age. DADA2 syndrome encompasses pleiotropic manifestations such as stroke, systemic vasculitis, hematologic alterations, and immunodeficiency. Although skeletal abnormalities have been reported in patients with this disease, clear information about skeletal health, with appropriate biochemical-clinical characterization/management, its evolution over time and any appropriate clinical management is still insufficient. In this paper, after a general introduction shortly reviewing the pathophysiology of Ada2 enzymatic protein, its potential role in bone health, we describe a case study of two 27 year-old DADA2 monozygotic female twins exhibiting bone mineral density and bone turnover rate abnormalities over the years of their clinical follow-up.     

Stem Cell Aligned Growth Induced by CeO2 Nanoparticles in PLGA Scaffolds with Improved Bioactivity for Regenerative Medicine

Hybrid 2D polymeric–ceramic biosupports are fabricated by mixing a nanostructured CeO₂ powder with 85:15 poly(D,L ‐lactic‐co‐glycolic acid) (PLGA)/dichloromethane solutions at specific concentrations, followed by solvent casting onto pre‐patterned molds. The mold patterning allows the orientation of ceramic nanoparticles into parallel lines within the composite scaffold. The ability of the produced films to host and address cell growth is evaluated after 1, 3, and 6 days of culturing with murine derived cardiac and mesenchymal stem cells (CSCs and MSCs), and compared with PLGA films without ceramics and loaded with nanostructured TiO₂. Aligned cell growth is observed only for scaffolds that incorporate oriented ceramic nanoparticles, attributed to the nanoceramic ability to modulate the roughness pitch, thus improving cell sensitivity towards the host surface features. Better CSC and MSC proliferative activity is observed for CeO₂ composites with respect to either TiO₂‐added or unfilled PLGA films. This evidence may be related to the nanostructured CeO₂ antioxidative properties.     

Effects of zinc on molting and body weight of the estuarine crab Neohelice granulata (Brachyura: Varunidae)

The semiterrestrial burrowing crab Neohelice granulata is one of the main inhabitants of the supratidal and intertidal zones of brackish salt marshes, estuaries and coastal lagoons from South America's Atlantic littoral. A large population of this species spreads out Mar Chiquita coastal lagoon (in Argentina) and its corresponding wetlands, and is considered as a key species within this system.Since high values of dissolved heavy metals (including Zn) have been recently reported within Mar Chiquita coastal lagoon, with levels unusually higher than those from other coastal systems within Argentina, it has been explored that the existence of a risk of environmental conditions endanger these populations. So, juveniles of this estuarine crab were experimentally exposed to increasing concentrations of dissolved Zn (i.e., 0, 0.5 and 1 mg Zn²⁺ L^− 1) during six months, the time involved between two successive molts; in addition, both the size and weight reached after each molt were also studied in this assay. It can be concluded that zinc can be toxic to crabs only at high concentrations. Considering that levels up to 1 mg Zn L^− 1 were recently reported in Mar Chiquita coastal lagoon waters, the potential occurrence of mean chronic effects on the crab population within the coastal lagoon is discussed.     

The Absence of Extracellular Cold-Inducible RNA-Binding Protein (eCIRP) Promotes Pro-Angiogenic Microenvironmental Conditions and Angiogenesis in Muscle Tissue Ischemia

Extracellular Cold-inducible RNA-binding protein (eCIRP), a damage-associated molecular pattern, is released from cells upon hypoxia and cold-stress. The overall absence of extra- and intracellular CIRP is associated with increased angiogenesis, most likely induced through influencing leukocyte accumulation. The aim of the present study was to specifically characterize the role of eCIRP in ischemia-induced angiogenesis together with the associated leukocyte recruitment. For analyzing eCIRPs impact, we induced muscle ischemia via femoral artery ligation (FAL) in mice in the presence or absence of an anti-CIRP antibody and isolated the gastrocnemius muscle for immunohistological analyses. Upon eCIRP-depletion, mice showed increased capillary/muscle fiber ratio and numbers of proliferating endothelial cells (CD31⁺/CD45⁻/BrdU⁺). This was accompanied by a reduction of total leukocyte count (CD45⁺), neutrophils (MPO⁺), neutrophil extracellular traps (NETs) (MPO⁺CitH3⁺), apoptotic area (ascertained via TUNEL assay), and pro-inflammatory M1-like polarized macrophages (CD68⁺/MRC1⁻) in ischemic muscle tissue. Conversely, the number of regenerative M2-like polarized macrophages (CD68⁺/MRC1⁺) was elevated. Altogether, we observed that eCIRP depletion similarly affected angiogenesis and leukocyte recruitment as described for the overall absence of CIRP. Thus, we propose that eCIRP is mainly responsible for modulating angiogenesis via promoting pro-angiogenic microenvironmental conditions in muscle ischemia.     

Study of the thermal transformations of Co- and Fe-exchanged zeolites A and X by “in situ” XRD under reducing atmosphere

“In situ” high temperature X-ray diffraction under reducing atmosphere is used for the first time to study the thermal stability and transformations of Co- and Fe-exchanged A and X zeolites. TG-DTA and “ex situ” XRD characterization were also carried out.The temperature of incipient crystallization of metallic phase was found to be 700 °C in Fe-zeolites and 800 °C in Co-zeolites. Moreover, ex situ X-ray experiments, after thermal treatment both under inert and reducing atmosphere, revealed the formation of ceramic phases upon the thermal collapse of the zeolitic framework. Metal nanoparticles were obtained by reduction and the size of metal clusters was found to range between 24 and 40 nm.     

The Human Microbiomes in Pancreatic Cancer: Towards Evidence-Based Manipulation Strategies?

Recent pieces of evidence have emerged on the relevance of microorganisms in modulating responses to anticancer treatments and reshaping the tumor-immune microenvironment. On the one hand, many studies have addressed the role of the gut microbiota, providing interesting correlative findings with respect to etiopathogenesis and treatment responses. On the other hand, intra-tumoral bacteria are being recognized as intrinsic and essential components of the cancer microenvironment, able to promote a plethora of tumor-related aspects from cancer growth to resistance to chemotherapy. These elements will be probably more and more valuable in the coming years in early diagnosis and risk stratification. Furthermore, microbial-targeted intervention strategies may be used as adjuvants to current therapies to improve therapeutic responses and overall survival. This review focuses on new insights and therapeutic approaches that are dawning against pancreatic cancer: a neoplasm that arises in a central metabolic “hub” interfaced between the gut and the host.     

Synergistic antioxidant and antibacterial activity of rosemary plus butylated derivatives

Antioxidant and antibacterial activity of a methanol rosemary extract (RE) containing 30% carnosic acid (CA), 16% carnosol (COH) and 5% rosmarinic acid (RA) was studied in vitro alone and in combination with the antioxidant food additives butylated hydroxytoluene (BHT) and butylated hydroxyanisole (BHA). The antioxidant efficiency of the extract, CA, and RA, was determined by a kinetic analysis of the 2,2-diphenyl-2-picrylhydrazyl hydrate radical (DPPH·) scavenging activity. RE showed two different rate slopes in the reduction of DPPH· vs. time curve, which correlated with the distinct behaviours of RA and CA; pure RA reached the plateau more rapidly than CA. A synergistic antioxidant effect between RE and BHT was demonstrated by isobolographic analysis and a synergistic interaction of RE with BHA to inhibit Escherichia coli and Staphylococcus aureus growth was observed. Therefore, rosemary not only enhances the antioxidant efficiency of BHA and BHT, but also the antibacterial effect of BHA; allowing a decrease from 4.4 to17 folds in the amounts of the synthetic compounds used.