Alberto Dinarello  Annachiara Tesoriere  Paolo Martini  Camilla Maria Fontana  Davide Volpato  Lorenzo Badenetti  Francesca Terrin  Nicola Facchinello  Chiara Romualdi  Oliana Carnevali  Luisa Dalla Valle  Francesco Argenton 《International journal of molecular sciences》2022,23(5)

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Nunzio Antonio Cacciola  Angela Salzano  Nunzia D&#x;Onofrio  Tommaso Venneri  Paola De Cicco  Francesco Vinale  Orsolina Petillo  Manuela Martano  Paola Maiolino  Gianluca Neglia  Ciro Campanile  Lorella Severino  Carmine Merola  Francesca Borrelli  Maria Luisa Balestrieri  Giuseppe Campanile 《International journal of molecular sciences》2022,23(15)

Recent pharmacological research on milk whey, a byproduct of the dairy industry, has identified several therapeutic properties that could be exploited in modern medicine. In the present study, we investigated the anticancer effects of whey from Mediterranean buffalo (Bubalus bubalis) milk. The antitumour effect of delactosed milk whey (DMW) was evaluated using the HCT116 xenograft mouse model of colorectal cancer (CRC). There were no discernible differences in tumour growth between treated and untreated groups. Nevertheless, haematoxylin and eosin staining of the xenograft tissues showed clearer signs of different cell death in DMW-treated mice compared to vehicle-treated mice. Detailed biochemical and molecular biological analyses revealed that DMW was able to downregulate the protein expression levels of c-myc, phospho-Histone H3 (ser 10) and p-ERK. Moreover, DMW also activated RIPK1, RIPK3, and MLKL axis in tumour tissues from xenograft mice, thus, suggesting a necroptotic effect. The necroptotic pathway was accompanied by activation of the apoptotic pathway as revealed by increased expression of both cleaved caspase-3 and PARP-1. At the molecular level, DMW-induced cell death was also associated with (i) upregulation of SIRT3, SIRT6, and PPAR-γ and (ii) downregulation of LDHA and PPAR-α. Overall, our results unveil the potential of whey as a source of biomolecules of food origin in the clinical setting of novel strategies for the treatment of CRC.  相似文献   

    

Maria Consiglia Trotta  Carlo Gesualdo  Hildegard Herman  Sami Gharbia  Cornel Balta  Caterina Claudia Lepre  Marina Russo  Annalisa Itro  Giovanbattista D&#x;Amico  Luisa Peluso  Iacopo Panarese  Gorizio Pieretti  Giuseppe Ferraro  Francesca Simonelli  Michele D&#x;Amico  Settimio Rossi  Anca Hermenean 《International journal of molecular sciences》2022,23(17)

Background: Diabetic retinopathy (DR) is a neurovascular disease, characterized by a deficiency of brain-derived neurotrophic factor (BDNF), a regulator of autophagy. Beta-hydroxybutyrate (BHB), previously reported as a protective agent in DR, has been associated with BDNF promotion. Here, we investigated whether systemic BHB affects the retinal levels of BDNF and local autophagy in diabetic mice with retinopathy; Methods: C57BL/6J mice were administered with intraperitoneal (i.p.) streptozotocin (STZ) (75 mg/kg) injection to develop diabetes. After 2 weeks, they received i.p. injections of BHB (25–50–100 mg/kg) twice a week for 10 weeks. Retinal samples were collected in order to perform immunofluorescence, Western blotting, and ELISA analysis; Results: BHB 50 mg/kg and 100 mg/kg significantly improved retinal BDNF levels (p < 0.01) in diabetic mice. This improvement was negatively associated with autophagosome–lysosome formations (marked by LC3B and ATG14) and to higher levels of connexin 43 (p < 0.01), a marker of cell integrity. Moreover, BHB administration significantly reduced M1 microglial activation and autophagy (p < 0.01); Conclusions: The systemic administration of BHB in mice with DR improves the retinal levels of BDNF, with the consequent reduction of the abnormal microglial autophagy. This leads to retinal cell safety through connexin 43 restoration.  相似文献   

    

Diego Camuzi  Luisa Aguirre Buexm  Simone de Queiroz Chaves Loureno  Rachele Grazziotin  Simone Guaraldi  Priscila Valverde  Davy Rapozo  Jill M. Brooks  Hisham Mehanna  Luis Felipe Ribeiro Pinto  Sheila Coelho Soares-Lima 《International journal of molecular sciences》2022,23(14)

Squamous cell carcinoma is the main histological tumor type in the upper aerodigestive tract (UADT), including the esophagus (ESCC) and the head and neck sites, as well as the oral cavity (OCSCC), larynx (LSCC) and oropharynx (OPSCC). These tumors are induced by alcohol and tobacco exposure, with the exception of a subgroup of OPSCC linked to human papillomavirus (HPV) infection. Few genes are frequently mutated in UADT tumors, pointing to other molecular mechanisms being involved during carcinogenesis. The F-box and leucine-rich repeat protein 7 (FBXL7) is a potential tumor-suppressing gene, one that is frequently hypermethylated in pancreatic cancer and where the encoded protein promotes the degradation of AURKA, BIRC5 and c-SRC. Thus, the aim of this study was to evaluate the methylation and expression profile of FBXL7 in the UADT and the gene’s association with the clinical, etiological and pathological characteristics of patients, as well as the expression of its degradation targets. Here we show that the FBXL7 gene’s body is hypomethylated in the UADT, independently of histology, but not in virus-associated tumors. FBXL7 body methylation and gene expression levels were correlated in the ESCC, LSCC, OCSCC and OPSCC. Immunohistochemistry analysis showed that FBXL7 protein levels are not correlated with the levels of its degradation targets, AURKA and BIRC5, in the UADT. The high discriminatory potential of FBXL7 body hypomethylation between non-tumor and tumor tissues makes it a promising biomarker.  相似文献   

    

Brisa Pea  Mostafa Adbel-Hafiz  Maria Cavasin  Luisa Mestroni  Orfeo Sbaizero 《International journal of molecular sciences》2022,23(7)

Arrhythmogenic cardiomyopathy (ACM) is an inherited heart muscle disorder characterized by progressive replacement of cardiomyocytes by fibrofatty tissue, ventricular dilatation, cardiac dysfunction, arrhythmias, and sudden cardiac death. Interest in molecular biomechanics for these disorders is constantly growing. Atomic force microscopy (AFM) is a well-established technic to study the mechanobiology of biological samples under physiological and pathological conditions at the cellular scale. However, a review which described all the different data that can be obtained using the AFM (cell elasticity, adhesion behavior, viscoelasticity, beating force, and frequency) is still missing. In this review, we will discuss several techniques that highlight the potential of AFM to be used as a tool for assessing the biomechanics involved in ACM. Indeed, analysis of genetically mutated cells with AFM reveal abnormalities of the cytoskeleton, cell membrane structures, and defects of contractility. The higher the Young’s modulus, the stiffer the cell, and it is well known that abnormal tissue stiffness is symptomatic of a range of diseases. The cell beating force and frequency provide information during the depolarization and repolarization phases, complementary to cell electrophysiology (calcium imaging, MEA, patch clamp). In addition, original data is also presented to emphasize the unique potential of AFM as a tool to assess fibrosis in cardiac tissue.  相似文献   

    

Andrea Palermo  Laura Giannotti  Benedetta Di Chiara Stanca  Franco Ferrante  Antonio Gnoni  Paola Nitti  Nadia Calabriso  Christian Demitri  Fabrizio Damiano  Tiziano Batani  Massimo Lungherini  Maria Annunziata Carluccio  Biagio Rapone  Erda Qorri  Antonio Scarano  Luisa Siculella  Eleonora Stanca  Alessio Rochira 《International journal of molecular sciences》2022,23(23)

Edentulism is the condition of having lost natural teeth, and has serious social, psychological, and emotional consequences. The need for implant services in edentulous patients has dramatically increased during the last decades. In this study, the effects of concentrated growth factor (CGF), an autologous blood-derived biomaterial, in improving the process of osseointegration of dental implants have been evaluated. Here, permeation of dental implants with CGF has been obtained by using a Round up device. These CGF-coated dental implants retained a complex internal structure capable of releasing growth factors (VEGF, TGF-β1, and BMP-2) and matrix metalloproteinases (MMP-2 and MMP-9) over time. The CGF-permeated implants induced the osteogenic differentiation of human bone marrow stem cells (hBMSC) as confirmed by matrix mineralization and the expression of osteogenic differentiation markers. Moreover, CGF provided dental implants with a biocompatible and biologically active surface that significantly improved adhesion of endothelial cells on CGF-coated implants compared to control implants (without CGF). Finally, data obtained from surgical interventions with CGF-permeated dental implants presented better results in terms of optimal osseointegration and reduced post-surgical complications. These data, taken together, highlight new and interesting perspectives in the use of CGF in the dental implantology field to improve osseointegration and promote the healing process.  相似文献   

    

Giulia Lombardi  Roberta Valeria Latorre  Alessandro Mosca  Diego Calvanese  Luisa Tomasello  Christian Boni  Manuela Ferracin  Massimo Negrini  Nader Al Dewik  Mohamed Yassin  Mohamed A. Ismail  Bruno Carpentieri  Claudio Sorio  Paola Lecca 《International journal of molecular sciences》2022,23(17)

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Marcella Pesce  Luisa Seguella  Alessandro Del Re  Jie Lu  Irene Palenca  Chiara Corpetti  Sara Rurgo  Walter Sanseverino  Giovanni Sarnelli  Giuseppe Esposito 《International journal of molecular sciences》2022,23(10)

Engineered probiotics represent a cutting-edge therapy in intestinal inflammatory disease (IBD). Genetically modified bacteria have provided a new strategy to release therapeutically operative molecules in the intestine and have grown into promising new therapies for IBD. Current IBD treatments, such as corticosteroids and immunosuppressants, are associated with relevant side effects and a significant proportion of patients are dependent on these therapies, thus exposing them to the risk of relevant long-term side effects. Discovering new and effective therapeutic strategies is a worldwide goal in this research field and engineered probiotics could potentially provide a viable solution. This review aims at describing the proceeding of bacterial engineering and how genetically modified probiotics may represent a promising new biotechnological approach in IBD treatment.  相似文献   

    

Lucio Manzi  Nunzio Sepe  Walter Migliaccio  Ludovica Lanzoni  Luisa Iozzino  Fabrizia D&#x;Angelo  Lucia Colarusso  Susana Montenegro  Angelo Palmese  Thomas D&#x;Hooghe  Alfredo Ulloa-Aguirre  Yulia Koloda  Monica Lispi 《International journal of molecular sciences》2022,23(12)

Although the full primary structures of the alfa and beta subunits of reference r-hFSH-alfa and its biosimilars are identical, cell context-dependent differences in the expressing cell lines and manufacturing process can lead to variations in glycosylation profiles. In the present study, we compared the structural features of reference r-hFSH-alfa with those of five biosimilar preparations approved in different global regions outside Europe (Primapur^®, Jin Sai Heng^®, Follitrope^®, Folisurge^®, and Corneumon^®) with respect to glycosylation, macro- and microheterogeneity, and other post-translational modifications and higher order structure. The mean proportion of N-glycosylation-site occupancy was highest in reference r-hFSH-alfa, decreasing sequentially in Primapur, Jin Sai Heng, Corneumon, Follisurge and Follitrope, respectively. The level of antennarity showed slightly higher complexity in Corneumon, Primapur and Follitrope versus reference r-hFSH-alfa, whereas Jin Sai Heng and Folisurge were aligned with reference r-hFSH-alfa across all N-glycosylation sites. Sialylation level was higher in Corneumon and Follitrope, but small differences were detected in other biosimilar preparations compared with reference r-hFSH-alfa. Jin Sai Heng showed higher levels of N-glyconeuramic acid than the other preparations. Minor differences in oxidation levels were seen among the different products. Therefore, in summary, we identified var ious differences in N-glycosylation occupancy, antennarity, sialylation and oxidation between reference r-hFSH-alfa and the biosimilar preparations analyzed.  相似文献   

    

Luisa Agnello  Marcello Ciaccio 《International journal of molecular sciences》2022,23(20)

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