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Article ; Online: Cell starvation increases uptake of extracellular Thymosin β4 and its complexes with calcium.

Piludu, Marco / Pichiri, Giuseppina / Coni, Pierpaolo / Piras, Monica / Congiu, Terenzio / Faa, Gavino / Lachowicz, Joanna Izabela

International immunopharmacology

2023 Volume 116, Page(s) 109743

Abstract: Cell metastasis is the main cause of cancer mortality. Inhibiting early events during cell metastasis and invasion could significantly improve cancer prognosis, but the initial mechanisms of cell transition and migration are barely known. Calcium ... ...

Abstract	Cell metastasis is the main cause of cancer mortality. Inhibiting early events during cell metastasis and invasion could significantly improve cancer prognosis, but the initial mechanisms of cell transition and migration are barely known. Calcium regulates cell migration, whilst Thymosin β4 is a G-actin and iron binding peptide associated with tumor metastasis and ferroptosis. Under normal cell growth conditions, intracellular free calcium ions and Thymosin β4 concentrations are strictly regulated, and are not influenced by extracellular supplementation. However, cell starvation decreases intracellular Thymosin β4 and increases extracellular peptide uptake above the normal range. Unexpectedly, cell starvation significantly increases internalization of extracellular Ca
MeSH term(s)	Humans ; Calcium ; Cell Movement ; Thymosin/metabolism ; Neoplasms
Chemical Substances	Calcium (SY7Q814VUP) ; thymosin beta(4) (549LM7U24W) ; Thymosin (61512-21-8)
Language	English
Publishing date	2023-01-25
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2043785-7
ISSN	1878-1705 ; 1567-5769
ISSN (online)	1878-1705
ISSN	1567-5769
DOI	10.1016/j.intimp.2023.109743
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Article: Exploring cell surface markers and cell-cell interactions of human breast milk stem cells.

Coni, Pierpaolo / Piras, Monica / Piludu, Marco / Lachowicz, Joanna Izabela / Matteddu, Anna / Coni, Stefano / Reali, Alessandra / Fanos, Vassilios / Jaremko, Mariusz / Faa, Gavino / Pichiri, Giuseppina

Journal of public health research

2023 Volume 12, Issue 1, Page(s) 22799036221150332

Abstract: Background: Breakthrough studies have shown that pluripotent stem cells are present in human breast milk. The expression of pluripotency markers by breast milk cells is heterogeneous, relating to cellular hierarchy, from early-stage multi-lineage stem ... ...

Abstract	Background: Breakthrough studies have shown that pluripotent stem cells are present in human breast milk. The expression of pluripotency markers by breast milk cells is heterogeneous, relating to cellular hierarchy, from early-stage multi-lineage stem cells to fully differentiated mammary epithelial cells, as well as weeks of gestation and days of lactation. Design and methods: Here, we qualitatively analyze cell marker expression in freshly isolated human breast milk cells, without any manipulation that could influence protein expression. Moreover, we use electron microscopy to investigate cell-cell networks in breast milk for the first time, providing evidence of active intercellular communication between cells expressing different cellular markers. Results: The immunocytochemistry results of human breast milk cells showed positive staining in all samples for CD44, CD45, CD133, and Ki67 markers. Variable positivity was present with P63, Tβ4 and CK14 markers. No immunostaining was detected for Wt1, nestin, Nanog, OCT4, SOX2, CK5, and CD34 markers. Cells isolated from human breast milk form intercellular connections, which together create a cell-to-cell communication network. Conclusions: Cells freshly isolated form human breast milk, without particular manipulations, show heterogeneous expression of stemness markers. The studied milk staminal cells show "pluripotency" at different stages of differentiation, and are present as single cells or grouped cells. The adjacent cell interactions are evidenced by electron microscopy, which showed the formation of intercellular connections, numerous contact regions, and thin pseudopods.
Language	English
Publishing date	2023-01-24
Publishing country	United States
Document type	Journal Article
ISSN	2279-9028
ISSN	2279-9028
DOI	10.1177/22799036221150332
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Article ; Online: Generalized scleroderma-like induration associated with D-penicillamine elastosis perforans serpiginosa in Wilson's disease.

Atzori, Laura / Ferreli, Caterina / Agosta, Daniele / Mou, Marzia / Coni, Pierpaolo / Lachowicz, Joanna Izabela / Pilloni, Luca

International journal of dermatology

2022 Volume 62, Issue 2, Page(s) 246–249

MeSH term(s)	Humans ; Penicillamine/adverse effects ; Hepatolenticular Degeneration/complications ; Hepatolenticular Degeneration/drug therapy ; Skin Diseases/chemically induced ; Skin Diseases/drug therapy ; Skin Diseases/complications ; Scleroderma, Localized/chemically induced ; Scleroderma, Localized/diagnosis ; Scleroderma, Localized/drug therapy ; Scleroderma, Systemic/chemically induced ; Scleroderma, Systemic/drug therapy ; Scleroderma, Systemic/complications
Chemical Substances	Penicillamine (GNN1DV99GX)
Language	English
Publishing date	2022-08-15
Publishing country	England
Document type	Case Reports ; Journal Article
ZDB-ID	412254-9
ISSN	1365-4632 ; 0011-9059 ; 1461-1244
ISSN (online)	1365-4632
ISSN	0011-9059 ; 1461-1244
DOI	10.1111/ijd.16376
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Article ; Online: Study of the DNA binding mechanism and

Lachowicz, Joanna I / Mateddu, Anna / Coni, Pierpaolo / Caltagirone, Claudia / Murgia, Sergio / Gibson, Dan / Dalla Torre, Gabriele / Lopez, Xabier / Meloni, Federico / Pichiri, Giuseppina

Dalton transactions (Cambridge, England : 2003)

2022 Volume 51, Issue 16, Page(s) 6254–6263

Abstract: Metal ions have unique electrochemical and spectroscopical properties that cannot be attained by purely organic compounds. Most of the metal ions are toxic to humans, but paradoxically, metallodrugs are used in medicine as therapeutics and theranostics. ... ...

Abstract	Metal ions have unique electrochemical and spectroscopical properties that cannot be attained by purely organic compounds. Most of the metal ions are toxic to humans, but paradoxically, metallodrugs are used in medicine as therapeutics and theranostics. Metallodrugs are eliminated in urine and faeces, and therefore release toxic metals and ligands into aquatic ecosystems, thereby raising concerns regarding environmental risks. The use of metallodrugs based on essential metal ions (
MeSH term(s)	Aluminum/chemistry ; Coordination Complexes/pharmacology ; Copper/chemistry ; DNA ; Ecosystem ; Humans ; Ions ; Iron/chemistry ; Ligands ; Neoplasms ; Pyrones
Chemical Substances	Coordination Complexes ; Ions ; Ligands ; Pyrones ; kojic acid (6K23F1TT52) ; Copper (789U1901C5) ; DNA (9007-49-2) ; Aluminum (CPD4NFA903) ; Iron (E1UOL152H7)
Language	English
Publishing date	2022-04-20
Publishing country	England
Document type	Journal Article
ZDB-ID	1472887-4
ISSN	1477-9234 ; 1364-5447 ; 0300-9246 ; 1477-9226
ISSN (online)	1477-9234 ; 1364-5447
ISSN	0300-9246 ; 1477-9226
DOI	10.1039/d2dt00111j
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Article: Toward the renal vesicle: Ultrastructural investigation of the cap mesenchyme splitting process in the developing kidney.

Piras, Monica / Gerosa, Clara / Congiu, Terenzio / Cau, Flaviana / Fanni, Daniela / Pichiri, Giuseppina / Coni, Pierpaolo / Lachowicz, Joanna Izabela / Schirru, Enrico / Congia, Mauro / Rossino, Rossano / Muntoni, Sandro / Jaremko, Mariusz / Piludu, Marco

Journal of public health research

2022 Volume 11, Issue 4, Page(s) 22799036221124076

Abstract: Background: A complex sequence of morphogenetic events leads to the development of the adult mouse kidney. In the present study, we investigated the morphological events that characterize the early stages of the mesenchymal-to-epithelial transition of ... ...

Abstract	Background: A complex sequence of morphogenetic events leads to the development of the adult mouse kidney. In the present study, we investigated the morphological events that characterize the early stages of the mesenchymal-to-epithelial transition of cap mesenchymal cells, analyzing in depth the relationship between cap mesenchymal induction and ureteric bud (UB) branching. Design and methods: Normal kidneys of newborn non-obese diabetic (NOD) mice were excised and prepared for light and electron microscopic examination. Results: Nephrogenesis was evident in the outer portion of the renal cortex of all examined samples. This process was mainly due to the interaction of two primordial derivatives, the ureteric bud and the metanephric mesenchyme. Early renal developmental stages were initially characterized by the formation of a continuous layer of condensed mesenchymal cells around the tips of the ureteric buds. These caps of mesenchymal cells affected the epithelial cells of the underlying ureteric bud, possibly inducing their growth and branching. Conclusions: The present study provides morphological evidence of the reciprocal induction between the ureteric bud and the metanephric mesenchyme showing that the ureteric buds convert mesenchyme to epithelium that in turn stimulates the growth and the branching of the ureteric bud.
Language	English
Publishing date	2022-10-24
Publishing country	United States
Document type	Journal Article
ISSN	2279-9028
ISSN	2279-9028
DOI	10.1177/22799036221124076
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Article: Undercover Toxic Ménage à Trois of Amylin, Copper (II) and Metformin in Human Embryonic Kidney Cells.

Congiu, Terenzio / Alghrably, Mawadda / Emwas, Abdul-Hamid / Jaremko, Lukasz / Lachowicz, Joanna I / Piludu, Marco / Piras, Monica / Faa, Gavino / Pichiri, Giuseppina / Jaremko, Mariusz / Coni, Pierpaolo

Pharmaceutics

2021 Volume 13, Issue 6

Abstract: In recent decades, type 2 diabetes complications have been correlated with amylin aggregation, copper homeostasis and metformin side effects. However, each factor was analyzed separately, and only in some rare cases copper/amylin or copper/metformin ... ...

Abstract	In recent decades, type 2 diabetes complications have been correlated with amylin aggregation, copper homeostasis and metformin side effects. However, each factor was analyzed separately, and only in some rare cases copper/amylin or copper/metformin complexes were considered. We demonstrate for the first time that binary metformin/amylin and tertiary copper (II)/amylin/metformin complexes of high cellular toxicity are formed and lead to the formation of aggregated multi-level lamellar structures on the cell membrane. Considering the increased concentration of amylin, copper (II) and metformin in kidneys of T2DM patients, our findings on the toxicity of amylin and its adducts may be correlated with diabetic nephropathy development.
Language	English
Publishing date	2021-06-03
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527217-2
ISSN	1999-4923
ISSN	1999-4923
DOI	10.3390/pharmaceutics13060830
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Article ; Online: Living with the enemy: from protein-misfolding pathologies we know, to those we want to know.

Emwas, Abdul-Hamid / Alghrably, Mawadda / Dhahri, Manel / Sharfalddin, Abeer / Alsiary, Rawiah / Jaremko, Mariusz / Faa, Gavino / Campagna, Marcello / Congiu, Terenzio / Piras, Monica / Piludu, Marco / Pichiri, Giuseppina / Coni, Pierpaolo / Lachowicz, Joanna Izabela

Ageing research reviews

2021 Volume 70, Page(s) 101391

Abstract: Conformational diseases are caused by the aggregation of misfolded proteins. The risk for such pathologies develops years before clinical symptoms appear, and is higher in people with alpha-1 antitrypsin (AAT) polymorphisms. Thousands of people with ... ...

Abstract	Conformational diseases are caused by the aggregation of misfolded proteins. The risk for such pathologies develops years before clinical symptoms appear, and is higher in people with alpha-1 antitrypsin (AAT) polymorphisms. Thousands of people with alpha-1 antitrypsin deficiency (AATD) are underdiagnosed. Enemy-aggregating proteins may reside in these underdiagnosed AATD patients for many years before a pathology for AATD fully develops. In this perspective review, we hypothesize that the AAT protein could exert a new and previously unconsidered biological effect as an endogenous metal ion chelator that plays a significant role in essential metal ion homeostasis. In this respect, AAT polymorphism may cause an imbalance of metal ions, which could be correlated with the aggregation of amylin, tau, amyloid beta, and alpha synuclein proteins in type 2 diabetes mellitus (T2DM), Alzheimer's and Parkinson's diseases, respectively.
MeSH term(s)	Amyloid beta-Peptides ; Diabetes Mellitus, Type 2 ; Humans ; Islet Amyloid Polypeptide ; Parkinson Disease ; alpha 1-Antitrypsin Deficiency
Chemical Substances	Amyloid beta-Peptides ; Islet Amyloid Polypeptide
Language	English
Publishing date	2021-06-11
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2075672-0
ISSN	1872-9649 ; 1568-1637
ISSN (online)	1872-9649
ISSN	1568-1637
DOI	10.1016/j.arr.2021.101391
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Article ; Online: Thymosin β4 cytoplasmic/nuclear translocation as a new marker of cellular stress. A Caco2 case study.

Coni, Pierpaolo / Piras, Monica / Mateddu, Anna / Piludu, Marco / Orru, Germano / Scano, Alessandra / Cabras, Tiziana / Piras, Valentina / Lachowicz, Joanna Izabela / Jaremko, Mariusz / Faa, Gavino / Castagnola, Massimo / Pichiri, Giuseppina

RSC advances

2020 Volume 10, Issue 21, Page(s) 12680–12688

Abstract: Biomarkers of cell stress are important for proper diagnosis, and in studies of how cells respond to drug treatment. Biomarkers that respond early to pharmacological treatment could improve therapy by tailoring the treatment to the needs of the patient. ... ...

Abstract	Biomarkers of cell stress are important for proper diagnosis, and in studies of how cells respond to drug treatment. Biomarkers that respond early to pharmacological treatment could improve therapy by tailoring the treatment to the needs of the patient. Thymosin beta-4 (Tβ
Language	English
Publishing date	2020-03-30
Publishing country	England
Document type	Journal Article
ISSN	2046-2069
ISSN (online)	2046-2069
DOI	10.1039/c9ra10365a
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Article: Evaluation of accuracy of one-step nucleic acid amplification (OSNA) in diagnosis of lymph node metastases of papillary thyroid carcinoma. Diagnostic study.

Medas, Fabio / Coni, Pierpaolo / Podda, Francesco / Salaris, Claudia / Cappellacci, Federico / Faa, Gavino / Calò, Pietro Giorgio

Annals of medicine and surgery (2012)

2019 Volume 46, Page(s) 17–22

Abstract: Background: The incidence of node metastases in papillary thyroid carcinoma (PTC) is high, ranging from 20% to 90%. Prophylactic central lymph node compartment dissection (CLND), suggested from the latest guidelines for high-risk tumors, meets ... ...

Abstract	Background: The incidence of node metastases in papillary thyroid carcinoma (PTC) is high, ranging from 20% to 90%. Prophylactic central lymph node compartment dissection (CLND), suggested from the latest guidelines for high-risk tumors, meets resistance due to the high incidence of postoperative complications. Recently, new molecular biologic techniques, such as One Step Nucleic Acid Amplification (OSNA), have spread widely, allowing to quickly isolate, amplify and quantify mRNA encoding for proteins selectively present in neoplastic cells, as Cytokeratine-19. The aim of this study is to evaluate the application of OSNA to intraoperative diagnosis of node metastases of PTC. Methods: We included in the study patients with preoperative diagnosis of PTC; from each patient one or more lymph nodes were collected. To assess OSNA accuracy, each lymph node was divided into two halves: the first one was analysed with histopathological and immunohistochemical examination, whereas the second was studied with OSNA. Results: Twenty-six lymph nodes from 13 patients were included in the study. Overall, OSNA sensitivity was 87.5%, specificity 94.4%, positive predictive value 87.5%, negative predictive value 94.4% and accuracy 92.8%. Discussion and conclusion: OSNA is effective in detecting lymph node metastases of PTC. Considering the high risk of complications in CLND, and the uncertain prognostic value of lymph node metastases of PTC, OSNA seems to be a promising tool to identify intraoperatively patients who may benefit from CLND.
Language	English
Publishing date	2019-08-21
Publishing country	England
Document type	Journal Article
ZDB-ID	2745440-X
ISSN	2049-0801
ISSN	2049-0801
DOI	10.1016/j.amsu.2019.08.006
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Article: Retrospective Comparative Analysis of KRAS G12C

Giampieri, Riccardo / Lupi, Alessio / Ziranu, Pina / Bittoni, Alessandro / Pretta, Andrea / Pecci, Federica / Persano, Mara / Giglio, Enrica / Copparoni, Cecilia / Crocetti, Sonia / Mandolesi, Alessandra / Faa, Gavino / Coni, Pierpaolo / Scartozzi, Mario / Berardi, Rossana

Frontiers in oncology

2021 Volume 11, Page(s) 736104

Abstract: Background: KRAS mutations in metastatic colorectal cancer (mCRC) define a subset of tumors that have primary resistance to anti-EGFR-based therapy. Data concerning whether different KRAS mutations may also have a prognostic value are lacking. ... ...

Abstract	Background: KRAS mutations in metastatic colorectal cancer (mCRC) define a subset of tumors that have primary resistance to anti-EGFR-based therapy. Data concerning whether different KRAS mutations may also have a prognostic value are lacking. Furthermore, novel KRAS G12C inhibitors are currently in development. The aim of our analysis was to compare response rates in patients treated with first-line chemotherapy doublet + Bevacizumab among different KRAS variants. Secondary end-points were progression free survival (PFS) and overall survival (OS). Methods: Patients with KRAS mutated mCRC treated with either FOLFIRI/FOLFOX/XELOX + Bevacizumab were eligible for enrollment. Patients whose tumor harbored NRAS mutations or that coexpressed also BRAF mutations were excluded from this retrospective analysis. Patients' individual data were collected from patients' records. Propensity score matching (nearest method, 1:2 ratio) was used to define the two different groups of patients for comparison (KRAS G12C mutated Results: A total of 120 patients were assessed in the final analysis. Out of the 120 patients, 15 (12%) were KRAS G12C mutated. In the whole cohort of patients, 59/120 (49%) had partial response (PR), 42/120 (35%) had stable disease (SD), and 19/120 (16%) had progressive disease (PD) as the best response. In KRAS G12C patients, 4/15 (27%) had PR, 6/15 (40%) had SD, and the remaining 5/15 (33%) had PD as the best response. In patients with other KRAS mutations, 55/105 (52%) had PR, 37/105 (35%) had SD, and the remaining 13/105 (12%) had PD as the best response. The difference in RR between the two groups of patients was statistically significant (p=0.017). On the other hand, no difference in PFS (p=0.76) and OS (p=0.56) was observed. After matching procedures, the difference in response rates between KRAS G12C mutated patients Conclusions: In our cohort of patients, it was observed that KRAS G12C mutations are associated with worse response rates compared to other KRAS variants when treated with standard chemotherapy doublet + Bevacizumab. On the other hand, both PFS and OS were not significantly different. Based on these findings, we believe that new treatment options focused on KRAS G12C inhibition should be tested mainly in first-line setting and in addition to standard chemotherapy doublet + Bevacizumab for mCRC patients, as they might "fill the gap" in response rates that was seen in our study.
Language	English
Publishing date	2021-09-30
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2021.736104
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