Massimiliano G Bianchi

University of Parma | UNIPR · Department of Medicine and Surgery

Bifidobacteria are recognized as health-promoting bacteria that reside in the human gut, helping in the digestion of fiber, preventing infections, and producing essential compounds like vitamins. To date, Bifidobacterium animalis subsp. lactis, together with Bifidobacterium adolescentis, Bifidobacterium bifidum, Bifidobacterium breve, and Bifidobac...

B‐cell precursor acute lymphoblastic leukaemia (BCP‐ALL) blasts strictly depend on the transport of extra‐cellular asparagine (Asn), yielding a rationale for L‐asparaginase (ASNase) therapy. However, the carriers used by ALL blasts for Asn transport have not been identified yet. Exploiting RS4;11 cells as BCP‐ALL model, we have found that cell Asn...

This study investigated the impact of in vivo available colon-mango (poly)phenols on stress-induced impairment of intestinal barrier function. Caco-2/HT29-MTX cells were incubated with six extracts of ileal fluid collected pre- and 4-8 h post-mango consumption before being subjected to inflammatory stress. (Poly)phenols in ileal fluids were analyse...

Members of the genus Bifidobacterium are among the first microorganisms colonizing the human gut. Among these species, strains of Bifidobacterium breve are known to be commonly transmitted from mother to her newborn, while this species has also been linked with activities supporting human wellbeing. In the current study, an in silico approach, guid...

Bifidobacteria are among the first microbial colonizers of the human gut, being frequently associated with human health-promoting activities. In the current study, an in silico methodology based on an ecological and phylogenomic-driven approach allowed the selection of a Bifidobacterium adolescentis prototype strain, i.e., B. adolescentis PRL2023,...

Amorphous silica nanoparticles (ASNP) are among the nanomaterials that are produced in large quantities. ASNP have been present for a long time in several fast-moving consumer products, several of which imply exposure of the gastrointestinal tract, such as toothpastes, food additives, drug excipients, and carriers. Consolidated use and experimental...

Bifidobacteria are commensal microorganisms that typically inhabit the mammalian gut, including that of humans. As they may be vertically transmitted, they commonly colonize the human intestine from the very first day following birth and may persist until adulthood and old age, although generally at a reduced relative abundance and prevalence compa...

The human organism is inhabited by trillions of microorganisms, known as microbiota, which are considered to exploit a pivotal role in the regulation of host health and immunity. Recent investigations have suggested a relationship between the composition of the human microbiota and COVID-19 infection, highlighting a possible role of bacterial commu...

SLC38A5/SNAT5 is a system N transporter that can mediate net inward or outward transmembrane fluxes of neutral amino acids coupled with Na+ (symport) and H+ (antiport). Its preferential substrates are amino acids with side chains containing amide (glutamine, and asparagine) or imidazole (histidine) groups, but also serine, glycine and alanine are t...

Although compositional variation in the gut microbiome during human development has been extensively investigated, strain-resolved dynamic changes remain to be fully uncovered. In the current study, shotgun metagenomic sequencing data of 12,415 fecal microbiomes from healthy individuals are employed for strain-level tracking of gut microbiota membe...

Oral administration of nanoparticles (NPs) is a promising strategy to overcome solubility and stability issues of many active compounds. However, this route faces major obstacles related to the hostile gastrointestinal (GI) environment, which impairs the efficacy of orally administered nanomedicines. Here, we propose nanocomposites as a promising a...

Multiple millennia of human evolution have shaped the chemical composition of breast milk toward an optimal human body fluid for nutrition and protection and for shaping the early gut microbiota of newborns. This biological fluid is composed of water, lipids, simple and complex carbohydrates, proteins, immunoglobulins, and hormones. Potential inter...

Bifidobacteria are extensively exploited for the formulation of probiotic food supplements due to their claimed ability to exert health-beneficial effects upon their host. However, most commercialized probiotics are tested and selected for their safety features rather than for their effective abilities to interact with the host and/or other intesti...

Background/purpose Testing of dental materials when in contact with innate immune cells has been so far hindered by the lack of proper in vitro models. Human primary monocyte-derived macrophages (MDMs) would be an excellent option to this aim. However, the inability to detach them from the tissue culture plates contrast the possibility to culture t...

CdS QDs activate calcium signaling and apoptosis in HepG2 human hepatocytes. CdS QDs trigger inflammatory response and autophagy in THP-1 human macrophages.

The genomic era has resulted in the generation of a massive amount of genetic data concerning the genomic diversity of bacterial taxa. As a result, the microbiological community is increasingly looking for ways to define reference bacterial strains to perform experiments that are representative of the entire bacterial species. Despite this, there i...

Amorphous silica nanoparticles (ASNP) are present in a variety of products and their biological effects are actively investigated. Although several studies have documented pro-inflammatory effects of ASNP, the possibility that they also modify the response of innate immunity cells to natural activators has not been thoroughly investigated. Here, we...

Background: Clinical and experimental evidence point to a dysregulated immune response caused by SARS-CoV-2 as the primary mechanism of lung disease in COVID-19. However, the pathogenic mechanisms underlying COVID-19-associated ARDS (Acute Respiratory Distress Syndrome) remain incompletely understood. This study aims to explore the inflammatory re...

Mechanisms underlying the resistance of Acute Lymphoblastic Leukemia (ALL) blasts to L-asparaginase are still incompletely known. Here we demonstrate that human primary bone marrow mesenchymal stromal cells (MSCs) successfully adapt to L-asparaginase and markedly protect leukemic blasts from the enzyme-dependent cytotoxicity through an amino acid t...

Within the bone marrow hematopoietic cells are in close connection with mesenchymal stromal cells (MSCs), which influence the behavior and differentiation of normal or malignant lymphoid and myeloid cells. Altered cell metabolism is a hallmark of cancer, and changes in nutrient pools and fluxes are important components of the bidirectional communic...

Multiple myeloma (MM) cells consume huge amounts of glutamine and, as a consequence, the amino acid concentration is lower-than-normal in the bone marrow (BM) of MM patients. Here we show that MM-dependent glutamine depletion induces glutamine synthetase in stromal cells, as demonstrated in BM biopsies of MM patients, and reproduced in vitro by co-...

Previous work has demonstrated that precipitated (NM-200) and pyrogenic (NM-203) Amorphous Silica Nanoparticles (ASNPs) elicit the inflammatory activation of murine macrophages, with more pronounced effects observed with NM-203. Here, we compare the effects of low doses of NM-200 and NM-203 on human macrophage-like THP-1 cells, assessing how the pr...

In vitro studies have consistently shown that titanium surface wettability affects the response of osteoprogenitors, leading to important advances in the clinical osseointegration of dental implants. However, the underlying molecular mechanisms remain unknown. Since surface conditioning by blood components initiates within milliseconds after insert...

The data included in this paper are associated with a research article entitled 'Differences in toxicity, mitochondrial function and miRNome in human cells exposed in vitro to Cd as CdS quantum dots or ionic Cd' [1]. The article concerns the use of miRNAs as biomarkers for engineered nanomaterials (ENMs) risk assessment. Two different type of human...

The inability of cells to adapt to increased environmental tonicity can lead to inflammatory gene expression and pathogenesis. The Rel family of transcription factors TonEBP and NF-κB p65 play critical roles in the switch from osmoadaptive homeostasis to inflammation, respectively. Here we identified PACT-mediated PKR kinase activation as a marker...

The inability of cells to adapt to increased environmental tonicity can lead to inflammatory gene expression and pathogenesis. The Rel family of transcription factors TonEBP and NF-κB p65 play critical roles in the switch from osmoadaptive homeostasis to inflammation, respectively. Here we identified PACT-mediated PKR kinase activation as a marker...

The inability of cells to adapt to increased environmental tonicity can lead to inflammatory gene expression and pathogenesis. The Rel family of transcription factors TonEBP and NF-κB p65 play critical roles in the switch from osmoadaptive homeostasis to inflammation, respectively. Here we identified PACT-mediated PKR kinase activation as a marker...

[This corrects the article DOI: 10.1371/journal.pone.0228568.].

In cultured human fibroblasts, SNAT transporters (System A) account for the accumulation of non-essential neutral amino acids, are adaptively up-regulated upon amino acid deprivation and play a major role in cell volume recovery upon hypertonic stress. No information is instead available on the expression and activity of SNAT transporters in human...

In human, OCTN2 (SLC22A5) and ATB0,+ (SLC6A14) transporters mediate the uptake of L-carnitine, essential for the transport of fatty acids into mitochondria and the subsequent degradation by β-oxidation. Aim of the present study was to characterize L-carnitine transport in EpiAirway™, a 3D organotypic in vitro model of primary human tracheal-bronchi...

Over the last decades, cerium oxide nanoparticles (CeO2 NPs) have gained great interest due to their potential applications, mainly in the fields of agriculture and biomedicine. Promising effects of CeO2 NPs are recently shown in some neurodegenerative diseases, but the mechanism of action of these NPs in Parkinson’s disease (PD) remains to be inve...

Asparagine Synthetase (ASNS) catalyzes the synthesis of the non-essential amino acid asparagine (Asn) from aspartate (Asp) and glutamine (Gln). ASNS expression is highly regulated at the transcriptional level, being induced by both the Amino Acid Response (AAR) and the Unfolded Protein Response (UPR) pathways. Lack of ASNS protein expression is a h...

Background: y+LAT1, encoded by SCL7A7, is the protein mutated in Lysinuric Protein Intolerance (LPI), a rare metabolic disease caused by a defective cationic amino acid (CAA, arginine, lysine, ornithine) transport at the basolateral membrane of intestinal and renal tubular cells. The disease is characterized by protein-rich food intolerance with s...

Length and aspect ratio represent important toxicity determinants of fibrous nanomaterials. We have previously shown that anatase TiO2 nanofibers (TiO2 NF) cause a dose-dependent decrease of cell viability as well as the loss of epithelial barrier integrity in polarized airway cell monolayers. Herein we have investigated the impact of fiber shorten...

Metabolic alterations of cancer cells, aimed at sustaining their growth, may also influence the behavior of the tumor microenvironment. Our group has recently demonstrated that multiple myeloma (MM) is a highly glutamine(Gln)-addicted tumor that utilize huge amounts of Gln to fuel its metabolism through the enzyme glutaminase (GLS). For this reason...

The host-material interface is a crucial relationship dictating the possibility of successful osseointegration in implant dentistry. The aim of the present study was to characterize the effects of plasma proteins pre-adsorption on the adhesion capacity of osteoblasts, which occurs immediately after implant insertion in vivo. After having pre-adsorb...

Objectives: To investigate how a thermal treatment to increase titanium wettability influences proteins adsorption from blood serum and osteoblasts responses. Methods: Titanium discs with machined or micro-rough profiles were thermally treated to obtain hydrophilic surfaces. The adsorption kinetics of two representative serum proteins were determin...

The possibility of counteracting inflammation-related barrier defects with dietary compounds such as (poly)phenols has raised much interest, but information is still scarce. We have investigated here if (+)-catechin (CAT) and procyanidin B2 (PB2), two main dietary polyphenols, protect the barrier function of intestinal cells undergoing inflammatory...

Multi-walled carbon nanotubes (MWCNT) have many outstanding physical and chemical properties that make them useful in many applications in nanotechnology. However, these properties are reported to be potentially harmful for the human body. The effects of low and realistic doses of three well-characterized preparations of MWCNT, obtained from the Jo...

In human, OCTN2 (SLC22A5) and ATB0,+ (SLC6A14) transporters mediate the uptake of L-carnitine, essential for the transport of fatty acids into mitochondria and the subsequent degradation by β-oxidation. Aim of the present study is to characterize L-carnitine transport in EpiAirway™, a 3D organotypic in vitro model of primary human tracheal-bronchia...

Robust cell adhesion is known to be necessary to promote cell colonization of biomaterials and differentiation of progenitors. In this paper, we propose the functionalization of Silicon Oxycarbide (SiOxCy) nanowires (NWs) with 3-mercaptopropyltrimethoxysilane (MPTMS), a molecule containing a terminal -SH group. The aim of this functionalization was...

A decisive step in cell-biomaterial interaction is represented by the adsorption of proteins at the interface, whose fine control may be useful to trigger proper cell response. To this purpose, we can selectively control protein adsorption on biomaterials by means of aptamers. Aptamers selected to recognize fibronectin dramatically enhance chitosan...

L‐Asparaginase (ASNase) is one of the cornerstones of acute lymphoblastic leukaemia (ALL) treatment. Its antileukemic effect mainly relies on its ability to hydrolyse blood asparagine and glutamine. Asparagine depletion causes a severe nutritional stress in ALL blasts exhibiting low expression of asparagine synthetase (ASNS), which cannot, therefor...

A general model useful to assess the applicability, in terms of safety and efficiency, of nanosilver sols in real applications was developed. This led to the definition of an operative parameter, named Quality Index (QI), able to rank the capacity of the samples to be applied effectively in safe concentration ranges on the basis of the mere knowled...

In cells derived from several types of cancer, a transcriptional program drives high consumption of glutamine (Gln), which is used for anaplerosis, leading to a metabolic addiction for the amino acid. Low or absent expression of Glutamine Synthetase (GS), the only enzyme that catalyzes de novo Gln synthesis, has been considered a marker of Gln-addi...

It is known that the adsorption of bioactive molecules provides engineered nanoparticles (NPs) with novel biological activities. However, the biological effects of the adsorbed molecules may also be modified by the interaction with NP. Bacterial lipopolysaccharide (LPS), a powerful pro-inflammatory compound, is a common environmental contaminant an...

L-γ-Glutamyl-p-nitroanilide (GPNA) is widely used to inhibit the glutamine transporter ASCT2, although it is known that it also inhibits other sodium-dependent amino acid transporters. In a panel of human cancer cell lines, which express the system L transporters LAT1 and LAT2, GPNA inhibits the sodium-independent influx of leucine and glutamine. T...

H.M. Goldman Prize Session

High extracellular osmolarity results in a switch from an adaptive to an inflammatory gene expression program. We show that hyperosmotic stress activates the protein kinase R (PKR) independently of its RNA binding domain. In turn, PKR stimulated nuclear accumulation of nuclear factor-κB (NF-κB) p65 species phosphorylated at serine-536, which was pa...

The importance of glutamine (Gln) metabolism in multiple myeloma (MM) cells and its potential role as a therapeutic target are still unknown, although it has been reported that human myeloma cell lines (HMCLs) are highly sensitive to Gln depletion. In this study, we found that both HMCLs and primary bone marrow (BM) CD138(+) cells produced large am...

In a growing group of human cancers, glutamine (Gln) transport is considered a possible therapeutic target to achieve tumor control. However, Gln transport is mediated by several carriers in human cells, thus complicating the delineation of a strategy to obtain an effective intracellular shortage of the amino acid. To evaluate the feasibility of th...

Introduction The effect of low level laser therapy (LLLT) on the healing process could be useful for the prevention of post-extractive Bisphosphonate-related Osteonecrosis of the Jaws (BRONJ). The aim of the study was to investigate the effect of LLLT on the post-extractive socket healing in rats treated with zoledronic acid and dexamethasone. Mate...

Titanium dioxide (TiO2) nanofibres are a novel fibrous nanomaterial with increasing applications in a variety of fields. While the biological effects of TiO2 nanoparticles have been extensively studied, the toxicological characterization of TiO2 nanofibres is far from being complete. In this study, we evaluated the toxicity of commercially availabl...

The elucidation of toxicity determinants of Multi-Walled Carbon Nanotubes (MWCNTs) is still incomplete. Functionalization with carboxyl groups is, however, commonly used to mitigate MWCNT toxicity, although the rationale for the mitigating effect has not been fully clarified yet. In this work, two optimized chemical vapor deposition methods were em...

Amorphous Silica NanoParticles (ASNP) can be synthetized via several processes, two of which are the thermal route (to yield pyrogenic silica) and the wet route from a solution containing silicate salts (to obtain precipitated, colloidal, mesoporous silica or silica gel). Both methods of synthesis lead to ASNP that are applied as food additive (E55...

Although the pharmacological therapies for multiple sclerosis (MS) are focused on immunosuppression, additional approaches, aimed at counteracting oligodendrocyte injury, are gaining much interest. One of the most important mechanisms involved in MS-associated oligodendrocyte damage is glutamate-dependent excitotoxicity, which leads to oxidative st...

Laser therapy has been used for the prevention and management of medication-related ostenecrosis of the jaw (MRONJ). The aim of this paper was to investigate the action of laser therapy on extraction socket healing in rats in conditions at risk for MRONJ, evaluating the expression of markers of bone metabolism. Thirty male Sprague-Dawley rats were...

Cells respond to shrinkage induced by increased extracellular osmolarity via programmed changes in gene transcription and mRNA translation. The immediate response to this stress includes induction of expression of the neutral amino acid transporter SNAT2. Increased SNAT2-mediated uptake of neutral amino acids is an essential adaptive mechanism for...

Negativity for the astroglial marker Glutamine Synthetase (GS) is an histological hallmark of human oligodendrogliomas (OL). Given that GS accounts for the intracellular synthesis of glutamine (Gln), we hypothesized that OL cells are strictly dependent upon the availability of external Gln. To test this hypothesis, we compared the effects of severa...