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Article ; Online: Potential of Biofermentative Unsulfated Chondroitin and Hyaluronic Acid in Dermal Repair

Antonella D’Agostino / Annalisa La Gatta / Antonietta Stellavato / Donatella Cimini / Luisana Corsuto / Marcella Cammarota / Maria D’Agostino / Chiara Schiraldi

International Journal of Molecular Sciences, Vol 23, Iss 1686, p

2022 Volume 1686

Abstract: Chondroitin obtained through biotechnological processes (BC) shares similarities with both chondroitin sulfate (CS), due to the dimeric repetitive unit, and hyaluronic acid (HA), as it is unsulfated. In the framework of this experimental research, ... ...

Abstract	Chondroitin obtained through biotechnological processes (BC) shares similarities with both chondroitin sulfate (CS), due to the dimeric repetitive unit, and hyaluronic acid (HA), as it is unsulfated. In the framework of this experimental research, formulations containing BC with an average molecular size of about 35 KDa and high molecular weight HA (HHA) were characterized with respect to their rheological behavior, stability to enzymatic hydrolysis and they were evaluated in different skin damage models. The rheological characterization of the HHA/BC formulation revealed a G’ of 92 ± 3 Pa and a G″ of 116 ± 5 Pa and supported an easy injectability even at a concentration of 40 mg/mL. HA/BC preserved the HHA fraction better than HHA alone. BTH was active on BC alone only at high concentration. Assays on scratched keratinocytes (HaCaT) monolayers showed that all the glycosaminoglycan formulations accelerated cell migration, with HA/BC fastening healing 2-fold compared to the control. In addition, in 2D HaCaT cultures, as well as in a 3D skin tissue model HHA/BC efficiently modulated mRNA and protein levels of different types of collagens and elastin remarking a functional tissue physiology. Finally, immortalized human fibroblasts were challenged with TNF-α to obtain an in vitro model of inflammation. Upon HHA/BC addition, secreted IL-6 level was lower and efficient ECM biosynthesis was re-established. Finally, co-cultures of HaCaT and melanocytes were established, showing the ability of HHA/BC to modulate melanin release, suggesting a possible effect of this specific formulation on the reduction of stretch marks. Overall, besides demonstrating the safety of BC, the present study highlights the potential beneficial effect of HHA/BC formulation in different damage dermal models.
Keywords	chondroitin ; skin model ; hyaluronan gels ; wound healing ; ECM biomarkers ; striae distensae ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	500
Language	English
Publishing date	2022-02-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Black Edible Films from Protein-Containing Defatted Cake of Nigella sativa Seeds

Mohammed Sabbah / Mohammad Altamimi / Prospero Di Pierro / Chiara Schiraldi / Marcella Cammarota / Raffaele Porta

International Journal of Molecular Sciences, Vol 21, Iss 3, p

2020 Volume 832

Abstract: Black biodegradable/edible protein-based films were prepared from defatted cake waste obtained from Nigella sativa (black cumin) seeds as by-product of oil extraction process. The effects of pH, glycerol concentrations, and transglutaminase-catalyzed ... ...

Abstract	Black biodegradable/edible protein-based films were prepared from defatted cake waste obtained from Nigella sativa (black cumin) seeds as by-product of oil extraction process. The effects of pH, glycerol concentrations, and transglutaminase-catalyzed protein cross-linking activity on the stability of film-forming solutions were studied to determine the best experimental conditions to produce handleable films. Proteins contained in the analyzed defatted cake were shown to be able to act as transglutaminase acyl donor and acceptor substrates being polymerized when incubated in vitro in the presence of the enzyme. Film-forming solutions containing 20% glycerol and casted at pH 8.0 after treatment with the enzyme gave rise to morphologically more homogeneous films possessing mechanical and barrier properties, as well as antimicrobial activity, compatible with their possible applications as food packaging materials and mulching sheets. These findings confirm the validity of the strategy to consider the seed oil processed cakes as protein-based renewable sources to produce not only fertilizers, animal feed, or culinary food but also further valuable products such as bioplastics.
Keywords	nigella sativa ; protein-based films ; industrial biorenewables ; oil-seed waste ; transglutaminase ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	660
Language	English
Publishing date	2020-01-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Microgravity Induces Transient EMT in Human Keratinocytes by Early Down-Regulation of E-Cadherin and Cell-Adhesion Remodeling

Giulia Ricci / Alessandra Cucina / Sara Proietti / Simona Dinicola / Francesca Ferranti / Marcella Cammarota / Antonio Filippini / Mariano Bizzarri / Angela Catizone

Applied Sciences, Vol 11, Iss 110, p

2021 Volume 110

Abstract: Changes in cell–matrix and cell-to-cell adhesion patterns are dramatically fostered by the microgravity exposure of living cells. The modification of adhesion properties could promote the emergence of a migrating and invasive phenotype. We previously ... ...

Abstract	Changes in cell–matrix and cell-to-cell adhesion patterns are dramatically fostered by the microgravity exposure of living cells. The modification of adhesion properties could promote the emergence of a migrating and invasive phenotype. We previously demonstrated that short exposure to the simulated microgravity of human keratinocytes (HaCaT) promotes an early epithelial–mesenchymal transition (EMT). Herein, we developed this investigation to verify if the cells maintain the acquired invasive phenotype after an extended period of weightlessness exposure. We also evaluated cells’ capability in recovering epithelial characteristics when seeded again into a normal gravitational field after short microgravity exposure. We evaluated the ultra-structural junctional features of HaCaT cells by Transmission Electron Microscopy and the distribution pattern of vinculin and E-cadherin by confocal microscopy, observing a rearrangement in cell–cell and cell–matrix interactions. These results are mirrored by data provided by migration and invasion biological assay. Overall, our studies demonstrate that after extended periods of microgravity, HaCaT cells recover an epithelial phenotype by re-establishing E-cadherin-based junctions and cytoskeleton remodeling, both being instrumental in promoting a mesenchymal–epithelial transition (MET). Those findings suggest that cytoskeletal changes noticed during the first weightlessness period have a transitory character, given that they are later reversed and followed by adaptive modifications through which cells miss the acquired mesenchymal phenotype.
Keywords	simulated microgravity ; focal adhesion ; vinculin ; E-cadherin ; cytoskeleton ; HaCaT cells ; Technology ; T ; Engineering (General). Civil engineering (General) ; TA1-2040 ; Biology (General) ; QH301-705.5 ; Physics ; QC1-999 ; Chemistry ; QD1-999
Language	English
Publishing date	2021-12-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Polydatin Incorporated in Polycaprolactone Nanofibers Improves Osteogenic Differentiation

Stefania Lama / Amalia Luce / Giuseppe Bitti / Pilar Chacon-Millan / Annalisa Itro / Pasquale Ferranti / Giovanni D’Auria / Marcella Cammarota / Giovanni Francesco Nicoletti / Giuseppe Andrea Ferraro / Chiara Schiraldi / Michele Caraglia / Evzen Amler / Paola Stiuso

Pharmaceuticals, Vol 15, Iss 727, p

2022 Volume 727

Abstract: Polycaprolactone nanofibers are used as scaffolds in the field of tissue engineering for tissue regeneration or drug delivery. Polycaprolactone (PCL) is a biodegradable hydrophobic polyester used to obtain implantable nanostructures, which are clinically ...

Abstract	Polycaprolactone nanofibers are used as scaffolds in the field of tissue engineering for tissue regeneration or drug delivery. Polycaprolactone (PCL) is a biodegradable hydrophobic polyester used to obtain implantable nanostructures, which are clinically applicable due to their biological safety. Polydatin (PD), a glycosidic precursor of resveratrol, is known for its antioxidant, antitumor, antiosteoporotic, and bone regeneration activities. We aimed to use the osteogenic capacity of polydatin to create a biomimetic innovative and patented scaffold consisting of PCL-PD for bone tissue engineering. Both osteosarcoma cells (Saos-2) and mesenchymal stem cells (MSCs) were used to test the in vitro cytocompatibility of the PD-PCL scaffold. Reverse-phase (RP) HPLC was used to evaluate the timing release of PD from the PCL-PD nanofibers and the MTT assay, scanning electron microscopy, and alkaline phosphatase (ALP) activity were used to evaluate the proliferation, adhesion, and cellular differentiation in both osteosarcoma and human mesenchymal stem cells (MSCs) seeded on PD-PCL nanofibers. The proliferation of osteosarcoma cells (Saos-2) on the PD-PCL scaffold decreased when compared to cells grown on PLC nanofibers, whereas the proliferation of MSCs was comparable in both PCL and PD-PCL nanofibers. Noteworthy, after 14 days, the ALP activity was higher in both Saos-2 cells and MSCs cultivated on PD-PCL than on empty scaffolds. Moreover, the same cells showed a spindle-shaped morphology after 14 days when grown on PD-PCL as shown by SEM. In conclusion, we provide evidence that nanofibers appropriately coated with PD support the adhesion and promote the osteogenic differentiation of both human osteosarcoma cells and MSCs.
Keywords	osteosarcoma ; polydatin ; osteogenic differentiation ; mesenchymal stem cells ; polycaprolactone nanofibers ; Medicine ; R ; Pharmacy and materia medica ; RS1-441
Subject code	571
Language	English
Publishing date	2022-06-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Argan ( Argania spinosa L.) Seed Oil Cake as a Potential Source of Protein-Based Film Matrix for Pharmaco-Cosmetic Applications

Seyedeh Fatemeh Mirpoor / Concetta Valeria L. Giosafatto / Loredana Mariniello / Antonella D’Agostino / Maria D’Agostino / Marcella Cammarota / Chiara Schiraldi / Raffaele Porta

International Journal of Molecular Sciences, Vol 23, Iss 8478, p

2022 Volume 8478

Abstract: Various different agri-food biomasses might be turned into renewable sources for producing biodegradable and edible plastics, potentially attractive for food, agricultural and cosmeceutical sectors. In this regard, different seeds utilized for edible and ...

Abstract	Various different agri-food biomasses might be turned into renewable sources for producing biodegradable and edible plastics, potentially attractive for food, agricultural and cosmeceutical sectors. In this regard, different seeds utilized for edible and non-edible oil extraction give rise to high amounts of organic by-products, known as seed oil cakes (SOCs), potentially able to become protein-rich resources useful for the manufacturing of biodegradable films. This study reports the potential of SOC derived from Argania spinosa (argan), a well-known plant containing valuable non-refined oil suitable for food or cosmetic use, to be a promising valuable source for production of a protein-based matrix of biomaterials to be used in the pharmaco-cosmetic sector. Thus, glycerol-plasticized films were prepared by casting and drying using different amounts of argan seed protein concentrate, in the presence of increasing glycerol concentrations, and characterized for their morphological, mechanical, barrier, and hydrophilicity properties. In addition, their antioxidant activity and effects on cell viability and wound healing were investigated. The hydrophobic nature of the argan protein-based films, and their satisfying physicochemical and biological properties, suggest a biorefinery approach for the recycling of argan SOC as valuable raw material for manufacturing new products to be used in the cosmeceutical and food industries.
Keywords	argan seed oil ; seed oil cake ; protein-based film ; biomaterials ; cosmeceutical sector ; food coating ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	660
Language	English
Publishing date	2022-07-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Annurca apple polyphenol extract promotes mesenchymal-to-epithelial transition and inhibits migration in triple-negative breast cancer cells through ROS/JNK signaling

Daniela Cristina Vuoso / Stefania D’Angelo / Rosalia Ferraro / Sergio Caserta / Stefano Guido / Marcella Cammarota / Marina Porcelli / Giovanna Cacciapuoti

Scientific Reports, Vol 10, Iss 1, Pp 1-

2020 Volume 17

Abstract: Abstract Aberrant activation of epithelial-to-mesenchymal transition has been shown to correlate with triple-negative breast cancer (TNBC) progression and metastasis. Thus, the induction of the reverse process might offer promising opportunities to ... ...

Abstract	Abstract Aberrant activation of epithelial-to-mesenchymal transition has been shown to correlate with triple-negative breast cancer (TNBC) progression and metastasis. Thus, the induction of the reverse process might offer promising opportunities to restrain TNBC metastatic spreading and related mortality. Recently, the Annurca apple polyphenol extract (APE) has been highlighted as a multi-faceted agent that selectively kills TNBC cells by ROS generation and sustained JNK activation. Here, by qualitatively and quantitatively monitoring the real-time movements of live cells we provided the first evidence that APE inhibited the migration of MDA-MB-231 and MDA-MB-468 TNBC cells and downregulated metalloproteinase-2 and metalloproteinase-9. In MDA-MB-231 cells APE decreased SMAD-2/3 and p-SMAD-2/3 levels, increased E-cadherin/N-cadherin protein ratio, induced the switch from N-cadherin to E-cadherin expression and greatly reduced vimentin levels. Confocal and scanning electron microscopy imaging of APE-treated MDA-MB-231 cells evidenced a significant cytoskeletal vimentin and filamentous actin reorganization and revealed considerable changes in cell morphology highlighting an evident transition from the mesenchymal to epithelial phenotype with decreased migratory features. Notably, all these events were reverted by N-acetyl-l-cysteine and JNK inhibitor SP600125 furnishing evidence that APE exerted its effects through the activation of ROS/JNK signaling. The overall data highlighted APE as a potential preventing agent for TNBC metastasis.
Keywords	Medicine ; R ; Science ; Q
Subject code	616
Language	English
Publishing date	2020-09-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Glutamic Acid as Repeating Building Block for Bio-Based Films

Mohammed Sabbah / Prospero Di Pierro / Francesco Ruffo / Chiara Schiraldi / Alberto Alfano / Marcella Cammarota / Raffaele Porta

Polymers, Vol 12, Iss 1613, p

2020 Volume 1613

Abstract: Commercial inexpensive preparations of poly-γ-glutamic acid were used to obtain films made with a polypeptide constituted by a single repeating unit. The homopolymer was characterized by 1 H-NMR spectroscopy and thermogravimetry, as well as by zeta ... ...

Abstract	Commercial inexpensive preparations of poly-γ-glutamic acid were used to obtain films made with a polypeptide constituted by a single repeating unit. The homopolymer was characterized by 1 H-NMR spectroscopy and thermogravimetry, as well as by zeta potential and Z-average measurements. Manipulatable materials were obtained by casting film-forming solutions prepared at pH values between 3.0 and 4.0 and containing extensively dialyzed samples of the commercial product. The analysis of the mechanical properties highlighted a marked extensibility and plasticity of the films obtained without plasticizer, even though the addition of low amounts of glycerol (1–4%) was able to further increase these features. The characterization of poly-γ-glutamic acid molecular species, performed by membrane ultrafiltration and size-exclusion chromatography, coupled with triple-detection analysis of the obtained fractions, suggested that biopolymer chain length is responsible not only for its capacity to form film, but also for conferring to the films different features depending on the homopolymer molecular weight.
Keywords	poly-γ-glutamic acid ; bioplastics ; bio-based films ; Organic chemistry ; QD241-441
Subject code	660
Language	English
Publishing date	2020-07-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Biotechnological Transformation of Hydrocortisone into 16α-Hydroxyprednisolone by Coupling Arthrobacter simplex and Streptomyces roseochromogenes

Odile Francesca Restaino / Simona Barbuto Ferraiuolo / Addolorata Perna / Marcella Cammarota / Maria Giovanna Borzacchiello / Antonio Fiorentino / Chiara Schiraldi

Molecules, Vol 25, Iss 4912, p

2020 Volume 4912

Abstract: 16α-Hydroxyprednisolone, an anti-inflammatory drug, could be potentially obtained from hydrocortisone bioconversion by combining a 1,2-dehydrogenation reaction performed by Arthrobacter simplex ATCC 31652 with a 16α-hydroxylation reaction by Streptomyces ...

Abstract	16α-Hydroxyprednisolone, an anti-inflammatory drug, could be potentially obtained from hydrocortisone bioconversion by combining a 1,2-dehydrogenation reaction performed by Arthrobacter simplex ATCC 31652 with a 16α-hydroxylation reaction by Streptomyces roseochromogenes ATCC 13400. In this study we tested, for the first time, potential approaches to couple the two reactions using similar pH and temperature conditions for hydrocortisone bioconversion by the two strains. The A. simplex capability to 1,2-dehydrogenate the 16α-hydroxyhydrocortisone, the product of S. roseochromogenes transformation of hydrocortisone, and vice versa the capability of S. roseochromogenes to 16α-hydroxylate the prednisolone were assessed. Bioconversions were studied in shake flasks and strain morphology changes were observed by SEM. Whole cell experiments were set up to perform the two reactions in a sequential mode in alternate order or contemporarily at diverse temperature conditions. A. simplex catalyzed either the dehydrogenation of hydrocortisone into prednisolone efficiently or of 16α-hydroxyhydrocortisone into 16α-hydroxyprednisolone in 24 h (up to 93.9%). Surprisingly S. roseochromogenes partially converted prednisolone back to hydrocortisone. A 68.8% maximum of 16α-hydroxyprednisolone was obtained in 120-h bioconversion by coupling whole cells of the two strains at pH 6.0 and 26 °C. High bioconversion of hydrocortisone into 16α-hydroxyprednisolone was obtained for the first time by coupling A. simplex and S. roseochromogenes .
Keywords	Arthrobacter simplex ; bioconversion ; hydrocortisone ; 16α-hydroxyhydrocortisone ; 16α-hydroxyprednisolone ; prednisolone ; Organic chemistry ; QD241-441
Subject code	660
Language	English
Publishing date	2020-10-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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Article ; Online: Vanillin Affects Amyloid Aggregation and Non-Enzymatic Glycation in Human Insulin

Clara Iannuzzi / Margherita Borriello / Gaetano Irace / Marcella Cammarota / Antimo Di Maro / Ivana Sirangelo

Scientific Reports, Vol 7, Iss 1, Pp 1-

2017 Volume 14

Abstract: Abstract Curcumin is known for its anti-inflammatory, antioxidant and anticancer activity, as well as for its ability to interfere with amyloid aggregation and non-enzymatic glycation reaction, that makes it an attractive potential drug. However, ... ...

Abstract	Abstract Curcumin is known for its anti-inflammatory, antioxidant and anticancer activity, as well as for its ability to interfere with amyloid aggregation and non-enzymatic glycation reaction, that makes it an attractive potential drug. However, curcumin therapeutic use is limited because of its low systemic bioavailability and chemical stability as it undergoes rapid hydrolysis in physiological conditions. Recently, much attention has been paid to the biological properties of curcumin degradation products as potential bioactive molecules. Between them, vanillin, a natural vanilla extract, is a stable degradation product of curcumin that could be responsible for mediating its beneficial effects. We have analyzed the effect of vanillin, in comparison with curcumin, in the amyloid aggregation process of insulin as well as its ability to prevent the formation of the advanced glycation end products (AGEs). Employing biophysical, biochemical and cell based assays, we show that vanillin and curcumin similarly affect insulin amyloid aggregation promoting the formation of harmless fibrils. Moreover, vanillin restrains AGE formation and protects from AGE-induced cytotoxicity. Our novel findings not only suggest that the main health benefits observed for curcumin can be ascribed to its degradation product vanillin, but also open new avenues for developing therapeutic applications of curcumin degradation products.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2017-11-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
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Article ; Online: Acellular Dermal Matrix Used in Diabetic Foot Ulcers

Ferdinando Campitiello / Manfredi Mancone / Marcella Cammarota / Antonella D’Agostino / Giulia Ricci / Antonietta Stellavato / Angela Della Corte / Anna Virginia Adriana Pirozzi / Gianluca Scialla / Chiara Schiraldi / Silvestro Canonico

International Journal of Molecular Sciences, Vol 22, Iss 7085, p

Clinical Outcomes Supported by Biochemical and Histological Analyses

2021 Volume 7085

Abstract: Diabetic foot ulcer (DFU) is a diabetes complication which greatly impacts the patient’s quality of life, often leading to amputation of the affected limb unless there is a timely and adequate management of the patient. DFUs have a high economic impact ... ...

Abstract	Diabetic foot ulcer (DFU) is a diabetes complication which greatly impacts the patient’s quality of life, often leading to amputation of the affected limb unless there is a timely and adequate management of the patient. DFUs have a high economic impact for the national health system. Data have indeed shown that DFUs are a major cause of hospitalization for patients with diabetes. Based on that, DFUs represent a very important challenge for the national health system. Especially in developed countries diabetic patients are increasing at a very high rate and as expected, also the incidence of DFUs is increasing due to longevity of diabetic patients in the western population. Herein, the surgical approach focused on the targeted use of the acellular dermal matrix has been integrated with biochemical and morphological/histological analyses to obtain evidence-based information on the mechanisms underlying tissue regeneration. In this research report, the clinical results indicated decreased postoperative wound infection levels and a short healing time, with a sound regeneration of tissues. Here we demonstrate that the key biomarkers of wound healing process are activated at gene expression level and also synthesis of collagen I, collagen III and elastin is prompted and modulated within the 28-day period of observation. These analyses were run on five patients treated with Integra ® sheet and five treated with the injectable matrix Integra ® Flowable, for cavitary lesions. In fact, clinical evaluation of improved healing was, for the first time, supported by biochemical and histological analyses. For these reasons, the present work opens a new scenario in DFUs treatment and follow-up, laying the foundation for a tailored protocol towards complete healing in severe pathological conditions.
Keywords	diabetic foot ulcer ; biomaterials ; biochemical and histological analyses ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	616
Language	English
Publishing date	2021-06-01T00:00:00Z
Publisher	MDPI AG
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