A novel unbiased method reveals progressive podocyte globotriaosylceramide accumulation and loss with age in females with Fabry disease.

While females can suffer serious complications of Fabry disease, most studies are limited to males to avoid confounding by mosaicism. Here, we developed a novel unbiased method for quantifying globotriaosylceramide (GL3) inclusion volume in affected podocytes (F+) in females with Fabry disease independent of mosaicism leading to important new observations. All podocytes in male patients with Fabry are F+.

A Novel Multi-Axial Pressure Sensor Probe for Measuring Triaxial Stress States Inside Soft Materials.

This paper presents the concept, design, construction, and validation of a novel probe based on the hexadic disposition of six pressure sensors suitable for measuring triaxial stress states inside bulky soft materials. The measurement of triaxial stress states inside bulk materials such as brain tissue surrogates is a challenging task needed to investigate internal organs' stress states and validate FE models. The purpose of the work was the development and validation of a 17 × 17 × 17 mm probe containing six pressure sensors.

Dysregulated miRNA biogenesis downstream of cellular stress and ALS-causing mutations: a new mechanism for ALS.

Interest in RNA dysfunction in amyotrophic lateral sclerosis (ALS) recently aroused upon discovering causative mutations in RNA-binding protein genes. Here, we show that extensive down-regulation of miRNA levels is a common molecular denominator for multiple forms of human ALS. We further demonstrate that pathogenic ALS-causing mutations are sufficient to inhibit miRNA biogenesis at the Dicing step.

The p53 transcription factor modulates microglia behavior through microRNA-dependent regulation of c-Maf.

Neuroinflammation occurs in acute and chronic CNS injury, including stroke, traumatic brain injury, and neurodegenerative diseases. Microglia are specialized resident myeloid cells that mediate CNS innate immune responses. Disease-relevant stimuli, such as reactive oxygen species (ROS), can influence microglia activation.

A phase II trial of autologous transplantation of bone marrow stem cells for critical limb ischemia: results of the Naples and Pietra Ligure Evaluation of Stem Cells study.

Critical limb ischemia (CLI) is a vascular disease affecting lower limbs, which is going to become a demanding challenge because of the aging of the population. Despite advances in endovascular therapies, CLI is associated with high morbidity and mortality. Patients without direct revascularization options have the worst outcomes.

Differential migratory properties of monocytes isolated from human subjects naïve and non-naïve to Cannabis.

This study evaluates the migratory potential of monocytes isolated from two groups of human subjects: naïve and non-naïve to Cannabis. Phytocannabinoids (pCB), the bioactive agents produced by the plant Cannabis, regulate the phenotype and function of immune cells by interacting with CB1 and CB2 receptors. It has been shown that agents influencing the phenotype of circulating monocytes influence the phenotype of macrophages and the outcome of immune responses.

Successful bone marrow transplantation reveals the lack of endothelial progenitor cells mobilization in a patient with critical limb ischemia: a case report.

Restoring blood flow to ischemic tissue is a prerequisite for treatment of ischemic diseases. Cell-based therapy based on bone marrow transplantation is a promising option for patients with critical limb ischemia (CLI). The efficacy of cell therapies to augment neovascularization seems to involve endothelial progenitor cells (EPCs); however, the mechanisms underlying the efficacy have not been fully elucidated.

Beneficial effects of VEGF secreted from stromal cells in supporting endothelial cell functions: therapeutic implications for critical limb ischemia.

Critical limb ischemia (CLI) is the end stage of peripheral vascular disease (PVD). One third of CLI patients progresses to leg amputation with high associated morbidity and mortality. In no-option patients with end-stage critical limb ischemia, bone marrow cell transplantation has shown promising results, improving leg perfusion to the level of reducing major amputations and allowing limb salvage.

Distinct neuroinflammatory profile in post-mortem human Huntington's disease.

Neuroinflammation is a prominent feature of many neurodegenerative diseases, however, little is known about neuroinflammation in Huntington's disease. We used quantitative real time-PCR to compare the expression level of neuroinflammation-associated mediators in the striatum, cortex, and cerebellum from post-mortem Huntington's disease patient samples with controls. We found increased expression of several key inflammatory mediators, including CCL2 and IL-10, specifically in the striatum of Huntington's disease patients, the main area affected by this pathology.

Identification of serine/threonine kinase substrates in the human pathogen group B streptococcus.

All living organisms respond to changes in their internal and external environment for their survival and existence. Signaling is primarily achieved through reversible phosphorylation of proteins in both prokaryotes and eukaryotes. A change in the phosphorylation state of a protein alters its function to enable the control of cellular responses.

Beneficial effects of autologous bone marrow cell infusion and antioxidants/L-arginine in patients with chronic critical limb ischemia.

Background: Short-term (within 6 weeks follow-up) clinical studies indicate that implantation of bone marrow cells (BMCs) into ischemic limbs may improve peripheral ischemia. Here, the long-term safety and feasibility of intraarterial autologous BMCs with oral treatment with antioxidants and L-arginine were investigated in patients with critical ischemia on account of advanced atherosclerotic peripheral arterial disease (PAD).

Methods: Eighteen patients with PAD (advanced III/IV Fontaine stages) were enrolled in this study (NCT00306085).

Long-term effects of repeated autologous transplantation of bone marrow cells in patients affected by peripheral arterial disease.

Long-term effects of autologous mononuclear bone marrow cell transplantation were studied in patients with severe peripheral arterial disease (PAD) and critical limb ischemia. Ten patients with end-stage disease were infused twice with autologous bone marrow cells and they completed the 12-month follow-up study. Substantial improvement of blood flow and increasing capillary densities were seen when compared with a concomitant control group comprising patients who did not enroll in the study.

A novel pathogenic pathway of immune activation detectable before clinical onset in Huntington's disease.

Huntington's disease (HD) is an inherited neurodegenerative disorder characterized by both neurological and systemic abnormalities. We examined the peripheral immune system and found widespread evidence of innate immune activation detectable in plasma throughout the course of HD. Interleukin 6 levels were increased in HD gene carriers with a mean of 16 years before the predicted onset of clinical symptoms.

A thermostable alpha-galactosidase from Lactobacillus fermentum CRL722: genetic characterization and main properties.

Alpha-galactosidase (alpha-Gal) enzyme, which is encoded by the melA gene hydrolyzes alpha-1,6 galactoside linkages found in sugars, such as raffinose and stachyose. These alpha-galacto-oligosaccharides (alpha-GOS), which are found in large quantities in vegetables, such as soy, can cause gastrointestinal disorders in sensitive individuals because monogastric animals (including humans) do not posses alpha-Gal in the gut. The use of microbial alpha-Gal is a promising alternative to eliminate alpha-GOS in soy-derived products.

Regulation of cytotoxin expression by converging eukaryotic-type and two-component signalling mechanisms in Streptococcus agalactiae.

Signal transducing mechanisms are essential for regulation of gene expression in both prokaryotic and eukaryotic organisms. Regulation of gene expression in eukaryotes is accomplished by serine/threonine and tyrosine kinases and cognate phosphatases. In contrast, gene expression in prokaryotes is controlled by two-component systems that comprise a sensor histidine kinase and a cognate DNA binding response regulator.

Evaluation of peripheral blood neutrophil leucocytes in lead-exposed workers.

Background: Inorganic lead can interfere with humoral and especially cell-mediated immunity even at frequently occurring (<50 microg/dl) blood lead (Pb-B) levels. Occupational exposure to lead causes a primary impairment of the chemotactic and phagocytic activities of neutrophil leucocytes.

Objective: To verify whether, after taking into account the main confounding factors, occupational lead exposure is shown to induce changes in the number of blood neutrophil leucocytes, and to assess a possible dose-response relationship between Pb-B and the circulating neutrophil count in exposed workers.

[Assessment of neurobehavioral functions of workers exposed to low doses of metallic lead].

The effects of low-dose lead occupational exposure on neurobehavioral functions are still not well defined by international literature. The objective of this study is to assess by psychometric testing the presence of possible neuropsychological impairment in a group of male Italian workers with low blood lead levels in comparison to an adequate non exposed worker group. Given informed consent to take part to the study, all workers were interviewed about their working and clinical history and underwent determination of blood lead levels (PbB).

Regulation of purine biosynthesis by a eukaryotic-type kinase in Streptococcus agalactiae.

Group B streptococci (GBS) are the principal causal agents of human neonatal pneumonia, sepsis and meningitis. We had previously described the existence of a eukaryotic-type serine/threonine kinase (Stk1) and phosphatase (Stp1) in GBS that regulate growth and virulence of the pathogen. Our previous results also demonstrated that these enzymes reversibly phosphorylated an inorganic pyrophosphatase.

Reduction of non-digestible oligosaccharides in soymilk: application of engineered lactic acid bacteria that produce alpha-galactosidase.

Human consumption of soy-derived products has been limited by the presence of non-digestible oligosaccharides (NDO), such as the alpha-galactooligosaccharides raffinose and stachyose. Most mammals, including man, lack pancreatic alpha-galactosidase (alpha-Gal), which is necessary for the hydrolysis of these sugars. However, such NDO can be fermented by gas-producing microorganisms present in the cecum and large intestine, which in turn can induce flatulence and other gastrointestinal disorders in sensitive individuals.

Reduction of alpha-galactooligosaccharides in soyamilk by Lactobacillus fermentum CRL 722: in vitro and in vivo evaluation of fermented soyamilk.

Aims: Consumption of soya-derived products has been hampered by the presence of alpha-galactooligosaccharides (alpha-GOS) because mammals lack pancreatic alpha-galactosidase (alpha-Gal) which is necessary for their hydrolysis. These sugars thus reach the large intestine causing gastrointestinal disorders in sensitive individuals. The use of lactic acid bacteria (LAB) expressing alpha-Gal is a promising solution for the degradation of alpha-GOS in soyamilk.

[Effects on arterial pressure of exposure to low doses of inorganic lead: preliminary results].

The aim of this study is to evaluate the effects of occupational exposure to low inorganic lead (Pb) doses on blood pressure of exposed (E) workers. 44 workers of a foundry of lead wrecks and 14 workers employed in enameling and decoration of a manufacturing firm of artistic ceramics were examined. The group of non-exposed (NE) subjects is formed by 59 workers of packaging unit of a food industry.

Characterization of the melA locus for alpha-galactosidase in Lactobacillus plantarum.

Alpha-galactosides are abundant sugars in legumes such as soy. Because of the lack of alpha-galactosidase (alpha-Gal) in the digestive tract, humans are unable to digest these sugars, which consequently induce flatulence. To develop the consumption of the otherwise highly nutritional soy products, the use of exogenous alpha-Gal is promising.