Gcn5p and Ubp8p Affect Protein Ubiquitylation and Cell Proliferation by Altering the Fermentative/Respiratory Flux Balance in
            <i>Saccharomyces cerevisiae</i>

Palma, Antonella De; Fanelli, Giulia; Cretella, Elisabetta; Luca, Veronica De; Palladino, Raffaele Antonio; Panzeri, Valentina; Roffia, Valentina; Saliola, Michele; Mauri, Pierluigi; Filetici, Patrizia

doi:10.1128/mbio.01504-20

Cited by 7 publications

(9 citation statements)

References 44 publications

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“…The 48 proteins obtained from the SEQUEST algorithm were aligned, normalized and label-free compared. An in-house algorithm, namely, the Multidimensional Algorithm Protein Map (MAProMa) was employed to this aim, using the average peptide spectrum matches (aPSM) [ 111 , 112 ] that correspond to the average of all the spectra identified for a protein and, consequently, to its relative abundance, in each analyzed condition. In depth, to select differentially expressed proteins, subgroups (for both fetal- vs perinatal- hAFS-CM and hAFS-EVs, considering also hypoxic cell preconditioning stimulation), were pairwise compared applying a threshold of 0.4 and 5 on the two MAProMa indexes DAve (Differential Average) and DCI (Differential Confidence Index), respectively.…”

Section: Methodsmentioning

confidence: 99%

Comprehensive Profiling of Secretome Formulations from Fetal- and Perinatal Human Amniotic Fluid Stem Cells

Costa

Ceresa

Palma³

et al. 2021

IJMS

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We previously reported that c-KIT+ human amniotic-fluid derived stem cells obtained from leftover samples of routine II trimester prenatal diagnosis (fetal hAFS) are endowed with regenerative paracrine potential driving pro-survival, anti-fibrotic and proliferative effects. hAFS may also be isolated from III trimester clinical waste samples during scheduled C-sections (perinatal hAFS), thus offering a more easily accessible alternative when compared to fetal hAFS. Nonetheless, little is known about the paracrine profile of perinatal hAFS. Here we provide a detailed characterization of the hAFS total secretome (i.e., the entirety of soluble paracrine factors released by cells in the conditioned medium, hAFS-CM) and the extracellular vesicles (hAFS-EVs) within it, from II trimester fetal- versus III trimester perinatal cells. Fetal- and perinatal hAFS were characterized and subject to hypoxic preconditioning to enhance their paracrine potential. hAFS-CM and hAFS-EV formulations were analyzed for protein and chemokine/cytokine content, and the EV cargo was further investigated by RNA sequencing. The phenotype of fetal- and perinatal hAFS, along with their corresponding secretome formulations, overlapped; yet, fetal hAFS showed immature oxidative phosphorylation activity when compared to perinatal ones. The profiling of their paracrine cargo revealed some differences according to gestational stage and hypoxic preconditioning. Both cell sources provided formulations enriched with neurotrophic, immunomodulatory, anti-fibrotic and endothelial stimulating factors, and the immature fetal hAFS secretome was defined by a more pronounced pro-vasculogenic, regenerative, pro-resolving and anti-aging profile. Small RNA profiling showed microRNA enrichment in both fetal- and perinatal hAFS-EV cargo, with a stably- expressed pro-resolving core as a reference molecular signature. Here we confirm that hAFS represents an appealing source of regenerative paracrine factors; the selection of either fetal or perinatal hAFS secretome formulations for future paracrine therapy should be evaluated considering the specific clinical scenario.

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Section: Methodsmentioning

confidence: 99%

Comprehensive Profiling of Secretome Formulations from Fetal- and Perinatal Human Amniotic Fluid Stem Cells

Costa

Ceresa

Palma³

et al. 2021

IJMS

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“…The eluted peptides were directly characterized with a LTQ mass spectrometer equipped with a nano- ESI source (Thermo Fisher Scientific), which operated as previously described. 29 …”

Section: Methodsmentioning

confidence: 99%

“…For the correlation of experimental MS/MS spectra with the theoretical ones obtained by in silico digestion, the Homo Sapiens proteome database (73,660 entries) was downloaded from Uniprot in May 2019 ( www.uniprot.org ). The filtering criteria adopted were identical to those described by De Palma et al, 29 and set to get high identification confidence and a false discovery rate (FDR) of 0.01 based on q-values. 30 An in-house tool, MAProMa (Multidimensional Algorithm Protein Map), was employed to elaborate the output data so proteins could be compared and relative abundances evaluated in a label-free mode based of average spectral counts (aSpCs) among the examined conditions (Control, Caelyx, DOX-SiNPs and DOX-SiNPs-TZ).…”

Section: Methodsmentioning

confidence: 99%

“… 30 An in-house tool, MAProMa (Multidimensional Algorithm Protein Map), was employed to elaborate the output data so proteins could be compared and relative abundances evaluated in a label-free mode based of average spectral counts (aSpCs) among the examined conditions (Control, Caelyx, DOX-SiNPs and DOX-SiNPs-TZ). 31 In depth, considering the aSpCs and applying a threshold of 0.35 for DAve (Differential Average) and 4 for DCI (Differential Confidence Index) MAProMa indexes, 29 it was possible to extract the differentially expressed proteins for the three nanoparticle formulations with respect to the Control. Individual cellular function of the significantly dysregulated proteins was assigned according to the GOA database ( http://geneontology.org/ ) and the UniProt database ( http://www.uniprot.org/ ).…”

Section: Methodsmentioning

confidence: 99%

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99mTc-Radiolabeled Silica Nanocarriers for Targeted Detection and Treatment of HER2-Positive Breast Cancer

Rainone¹,

Palma²,

Sudati³

et al. 2021

IJN

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Introduction The overexpression of Human Epidermal Growth Factor Receptor 2 (HER2) is usually associated with aggressive and infiltrating breast cancer (BC) phenotype, and metastases. Functionalized silica-based nanocarriers (SiNPs) can be labeled for in vivo imaging applications and loaded with chemotherapy drugs, making possible the simultaneous noninvasive diagnosis and treatment (theranostic) for HER2-positive BC. Methods Firstly, FITC-filled SiNPs, were engineered with two different amounts of Hc-TZ (trastuzumab half-chain) per single nanoparticle (1:2 and 1:8, SiNPs to Hc-TZ ratio), which was 99m Tc-radiolabeled at histidine residues for ex vivo and in vivo biodistribution evaluations. Secondly, nanoparticles were loaded with DOX and their in vitro and ex vivo/in vivo delivery was assessed, in comparison with liposomal Doxorubicin (Caelyx). Finally, the treatment efficacy of DOX-SiNPs-TZ (1:8 Hc-TZ) was evaluated in vivo by PET and supported by MS-based proteomics profiling of tumors. Results SiNPs-TZ (1:8 Hc-TZ) tumor uptake was significantly greater than that of SiNPs-TZ (1:2 Hc-TZ) at 6 hours post-injection (p.i.) in ex vivo biodistribution experiment. At 24 h p.i., radioactivity values remained steady. Fluorescence microscopy, confirmed the presence of radiolabeled SiNPs-TZ (1:8 Hc-TZ) within tumor even at later times. SiNPs-TZ (1:8 Hc-TZ) nanoparticles loaded with Doxorubicin (DOX-SiNPs-TZ) showed a similar DOX delivery capability than Caelyx (at 6 h p.i.), in in vitro and ex vivo assays. Nevertheless, at the end of treatment, tumor volume was significantly reduced by DOX-SiNPs-TZ (1:8 Hc-TZ), compared to Caelyx and DOX-SiNPs treatment. Proteomics study identified 88 high stringent differentially expressed proteins comparing the three treatment groups with controls. Conclusion These findings demonstrated a promising detection specificity and treatment efficacy for our system (SiNPs-TZ, 1:8 Hc-TZ), encouraging its potential use as a new theranostic agent for HER2-positive BC lesions. In addition, proteomic profile confirmed that a set of proteins, related to tumor aggressiveness, were positively affected by targeted nanoparticles.

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“…Proteomics are widely used to investigate both tumor biomarkers and endotypes, such as the role of energy metabolism [ 102 , 103 ]. In contrast, few applications have been related to boron neutron capture therapy (BNCT).…”

Section: Proteomics For Predicting Outcomementioning

confidence: 99%

Theranostics in Boron Neutron Capture Therapy

Sauerwein

Sancey

Hey‐Hawkins

et al. 2021

Life

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Boron neutron capture therapy (BNCT) has the potential to specifically destroy tumor cells without damaging the tissues infiltrated by the tumor. BNCT is a binary treatment method based on the combination of two agents that have no effect when applied individually: 10B and thermal neutrons. Exclusively, the combination of both produces an effect, whose extent depends on the amount of 10B in the tumor but also on the organs at risk. It is not yet possible to determine the 10B concentration in a specific tissue using non-invasive methods. At present, it is only possible to measure the 10B concentration in blood and to estimate the boron concentration in tissues based on the assumption that there is a fixed uptake of 10B from the blood into tissues. On this imprecise assumption, BNCT can hardly be developed further. A therapeutic approach, combining the boron carrier for therapeutic purposes with an imaging tool, might allow us to determine the 10B concentration in a specific tissue using a non-invasive method. This review provides an overview of the current clinical protocols and preclinical experiments and results on how innovative drug development for boron delivery systems can also incorporate concurrent imaging. The last section focuses on the importance of proteomics for further optimization of BNCT, a highly precise and personalized therapeutic approach.

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Gcn5p and Ubp8p Affect Protein Ubiquitylation and Cell Proliferation by Altering the Fermentative/Respiratory Flux Balance in Saccharomyces cerevisiae

Cited by 7 publications

References 44 publications

Comprehensive Profiling of Secretome Formulations from Fetal- and Perinatal Human Amniotic Fluid Stem Cells

Comprehensive Profiling of Secretome Formulations from Fetal- and Perinatal Human Amniotic Fluid Stem Cells

99mTc-Radiolabeled Silica Nanocarriers for Targeted Detection and Treatment of HER2-Positive Breast Cancer

Theranostics in Boron Neutron Capture Therapy

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