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5th Anniversary of ‘Applied Biosciences and Bioengineering’ Section—Recent Advances in the Biochemistry of Inflammation

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A special issue of Applied Sciences (ISSN 2076-3417). This special issue belongs to the section "Applied Biosciences and Bioengineering".

Deadline for manuscript submissions: 20 September 2025 | Viewed by 15372

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Prof. Dr. Francesca Silvagno

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Department of Oncology, University of Torino, Via Santena 5 bis, 10126 Torino, Italy
Interests: cancer metabolism; vitamin D; TGF beta; mitochondrial metabolism; biochemistry; electromagnetic field; cancer growth; dermal wound healing; nutraceuticals
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Prof. Dr. Vittorio Gentile

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Department of Precision Medicine, Università degli Studi della Campania Luigi Vanvitelli, 80138 Naples, Italy
Interests: biochemistry and molecular biology of transglutaminases; neurodegeneration
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Special Issue Information

Dear Colleagues,

Inflammation is considered a driving force behind many chronic diseases, including cancer and neurodegenerative disease. Recently, cancer neuroscience has emerged as a new discipline focused on identifying and therapeutically targeting the interactions between the nervous system and cancer cells, both in the tumor microenvironment and at the systemic level. Inflammatory mediators exert a central role in this interplay, as their ability to quench and prevent inflammation can greatly benefit both cancer and neurological pathologies.

The aim of this Special Issue is to highlight the most recent advances in the biochemical approach to inflammation. This Special Issue will collect studies that cover the investigation of cellular targets and signaling pathway mediators of inflammation, the characterization of new anti-inflammatory agents and novel approaches that can challenge and defeat the chronic inflammatory stimulation that leads to neurodegeneration, pro-oncogenic transformation, and cancer progression. Of particular interest is the discovery and analysis of the neuroprotective effects of natural compounds and nutraceuticals against toxic insults and their antitumor activities through the modulation of genes responsible for inflammation and oxidative stress.

Prof. Dr. Francesca Silvagno
Prof. Dr. Vittorio Gentile
Guest Editors

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Keywords

inflammation
oxidative stress
inflammatory mediators
cancer
neuroscience
neurodegenerative disease
nutraceuticals

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Published Papers (9 papers)

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Research

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15 pages, 993 KiB

Open AccessArticle

Circulating Cell-Free Mitochondrial DNA and Inflammation in Older Adults with Pancreatic Cancer: Results from an Exploratory Study

by Giulia Girolimetti, Flora Guerra, Leonardo Henry Umberto Eusebi, Claudio Ricci, Emanuele Marzetti, Anna Picca and Cecilia Bucci

Appl. Sci. 2025, 15(8), 4410; https://doi.org/10.3390/app15084410 - 16 Apr 2025

Viewed by 230

Abstract

Pancreatic cancer (PaCa) is among the most aggressive malignancies of the digestive system. Inflammation plays a critical role in tumor growth and dissemination, with soluble cytokines serving as messengers that facilitate interactions between immune and cancer cells. The release of cell-free mitochondrial DNA (cf-mtDNA) into the bloodstream has been identified as a potent proinflammatory trigger, acting as a mitochondrial-derived damage-associated molecular pattern (mtDAMP). Whether a relationship exists between circulating cf-mtDNA (ccf-mtDNA) unloading and inflammation in PaCa remains unclear. In this study, we quantified ccf-mtDNA levels in plasma/serum samples from PaCa patients and healthy controls and examined their association with inflammatory markers. Analyses were conducted on 14 participants: 3 controls (mean age: 52.0 ± 16.0 years, 67% women) and 11 PaCa patients (mean age: 69.1 ± 10.0 years, 27% women). Circulating levels of ccf-mtDNA in PaCa patients did not show differences compared to controls (p = 0.06). In contrast, concentrations of interleukin (IL)-8, IL-17, and interferon-gamma were significantly higher in PaCa patients. Stratification of PaCa patients based on the median ccf-mtDNA concentration revealed significantly higher levels of IL-4, IL-9, monocyte chemoattractant protein-1 (MCP-1), and macrophage inflammatory protein 1-beta in those with ccf-mtDNA levels above the median (p < 0.05). Significant positive associations were also observed between levels of ccf-mtDNA and IL-8, fibroblast growth factor, and MCP-1. These results suggest a potential association between elevated ccf-mtDNA levels and increased concentrations of proinflammatory cytokines, especially in PaCa patients with an unfavorable prognosis. Further research with larger cohorts is required to validate these findings and assess the prognostic value of these biomarkers. Full article

(This article belongs to the Special Issue 5th Anniversary of ‘Applied Biosciences and Bioengineering’ Section—Recent Advances in the Biochemistry of Inflammation)

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19 pages, 2908 KiB

Open AccessArticle

Metabolic Dysfunction of Adipocytes Promotes the Secretion of Inflammatory TGFβ with Pro-Migratory Activity in Pancreatic Cancer

by Alice Albergamo, Loredana Bergandi, Iacopo Gesmundo, Elena Valente and Francesca Silvagno

Appl. Sci. 2025, 15(8), 4300; https://doi.org/10.3390/app15084300 - 13 Apr 2025

Viewed by 255

Abstract

Visceral fat mass is associated with a condition of chronic inflammation and can predispose the overweight to an increased cancer risk. Although it is known that adipocytes are active producers of the pro-inflammatory transforming growth factor β (TGFβ), the causes of their excessive synthesis are not clear. In this study, we reproduced two metabolic stress conditions frequently occurring in vivo, namely hypoxia and the fatty acid-driven metabolic uncoupling, and we characterized the response of an in vitro model of 3T3-L1 mouse adipocytes. For the first time, we demonstrated that the mitochondrial dysmetabolism of differentiated adipocytes induced the secretion of TGFβ. The paracrine activity of the secreted cytokine was then tested on two human pancreatic cancer cell lines. Cancer cells responded to the stimulation by increasing mitochondrial respiration, switching on the epithelial–mesenchymal transition (EMT) program and enhancing their motility. The data obtained in this proof-of-concept research show that TGFβ can be produced by dysmetabolic adipocytes, linking the altered metabolism with pro-tumorigenic inflammation. The novel observations of this study identify in metabolic stress a still unexplored cause of inflammation and cancer progression and pave the way to more detailed in vitro and clinical studies on pancreatic cancer. Full article

(This article belongs to the Special Issue 5th Anniversary of ‘Applied Biosciences and Bioengineering’ Section—Recent Advances in the Biochemistry of Inflammation)

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14 pages, 1346 KiB

Open AccessArticle

A Rheological Study of Creams and Gels Containing N-Acetyl Glucosamine in Nanoparticle Form: The Advantages of a Bioengineered Strategy for Natural Anti-Inflammatory Substance Vehiculation

by Alessia Mariano, Anna Scotto d’Abusco and Sergio Ammendola

Appl. Sci. 2024, 14(24), 11752; https://doi.org/10.3390/app142411752 - 17 Dec 2024

Viewed by 4629

Abstract

Topical formulations that include natural active compounds to treat inflamed and aching skin are favored by patients. Small local producers use commercial creams and gels to which they add compounds, often with criteria based more on trends than scientific evidence, to obtain products to treat inflamed joints or skin. Based on our previous studies that demonstrated the anti-inflammatory and analgesic effects of Harpagophytum procumbens extracts and N-acetylglucosamine, we were interested in preparing formulations with these natural substances for topical applications. In the present study, we compared the rheological properties of various creams and gels with bulk and nanoparticle forms of N-acetylglucosamine added, focusing on the flow properties of multiphase emulsion. Moreover, the ability of nanoparticles to reduce inflammation and stimulate collagen production was demonstrated in both chondrocyte and fibroblast spheroids. The results showed the activity of nano-N-acetylglucosamine in our cell models, suggesting its suitability for use as a component in creams and gels. Furthermore, its ability to affect the flow properties of commercial creams and gels makes it an ideal component of topical formulations for the treatment of inflamed skin and joints. Full article

(This article belongs to the Special Issue 5th Anniversary of ‘Applied Biosciences and Bioengineering’ Section—Recent Advances in the Biochemistry of Inflammation)

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14 pages, 5398 KiB

Open AccessArticle

Attenuating Oxidative Damage with Macelignan in Glutamate-Induced HT22 Hippocampal Cells

by Mei Tong He, Kiwon Jung, Chan-Woong Park, Young-Won Chin and Ki Sung Kang

Appl. Sci. 2024, 14(23), 11408; https://doi.org/10.3390/app142311408 - 7 Dec 2024

Viewed by 902

Abstract

Macelignan, from Myristica fragrans (nutmeg), is a bioactive compound with various pharmacological properties, including anti-inflammatory and neuroprotective activities. The purpose of this work was to investigate the antioxidant and anti-apoptotic effects of macelignan in glutamate-treated HT22 mouse hippocampal neurons. Macelignan was extracted and identified in a methanol extract of M. fragrans seeds. The DPPH was used to assess the antioxidative activity of macelignan. Glutamate (5 mM) was used to induce neurotoxicity in the HT22 cells. Neuroprotective effects were measured using relevant biochemical and imaging assays, including cell viability, ROS production, nuclear staining, apoptotic cell death, and protein expression. Macelignan markedly and concentration-dependently enhanced DPPH radical scavenging activity. In the HT22 cell model, glutamate induced cell damage by decreasing cell viability, promoting ROS generation, and increasing apoptotic cell death according to cell morphological changes. However, macelignan treatment restored cell viability, inhibited ROS generation concentration-dependently, and reduced apoptosis. Moreover, glutamate significantly up-regulated the phosphorylation of MAPK-pathway-related proteins, which was reversed by macelignan treatment. In conclusion, macelignan shows notable neuroprotective effects on oxidative stress and apoptotic cell death in glutamate-induced cells, and this study provides useful information on its potential therapeutic implications in neurological disorders. Full article

(This article belongs to the Special Issue 5th Anniversary of ‘Applied Biosciences and Bioengineering’ Section—Recent Advances in the Biochemistry of Inflammation)

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10 pages, 1780 KiB

Open AccessArticle

Inhibitory Effect of Dipeptides Containing Acidic Amino Acid Residue on Degranulation of RBL-2H3 Cells

by Kosuke Nishi, Taiki Hirakawa, Mitsumasa Izumi, Naoki Kageyama, Senri Yurue, Akari Ozaki, Yuki Toga, Momoko Ishida and Takuya Sugahara

Appl. Sci. 2024, 14(16), 7048; https://doi.org/10.3390/app14167048 - 11 Aug 2024

Viewed by 1634

Abstract

Upon degranulation, basophils and mast cells secrete an array of inflammatory mediators, including histamine, which leads to not only allergic inflammation but also other inflammatory diseases. We previously reported that an aqueous extract from enzyme-treated, dried sardine inhibits the degranulation of RBL-2H3 cells and attenuates the symptoms of Japanese cedar pollinosis in mice. This study evaluated an antiallergic effect of dipeptides containing acidic amino acid residue in an antigen-induced degranulation assay using RBL-2H3 cells. The result showed that acidic amino acid residue-containing dipeptides inhibit the degranulation of RBL-2H3 cells without cytotoxicity. Additionally, L-histidyl-L-glutamic acid (His-Glu), one of the acidic amino acid residue-containing dipeptides tested in this study, inhibited calcium ionophore-induced degranulation. We also found that His-Glu suppressed microtubule reorganization in RBL-2H3 cells after antigen stimulation. His-Glu slightly, but not significantly, suppressed the elevation of cytosolic calcium ion concentration leading to degranulation. Immunoblot analysis revealed that His-Glu significantly suppressed the phosphorylation of phosphoinositide 3-kinase and Akt, but not that of Syk or phospholipase Cγ. Overall results suggest that acidic amino acid residue-containing dipeptides can be used as food ingredients with an antiallergic effect. Full article

(This article belongs to the Special Issue 5th Anniversary of ‘Applied Biosciences and Bioengineering’ Section—Recent Advances in the Biochemistry of Inflammation)

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11 pages, 1095 KiB

Open AccessArticle

Endogenous Cannabinoids in Crohn’s Disease

by Michał S. Bochenek, Jan T. Tomasik, Andrzej Wędrychowicz and Przemysław J. Tomasik

Appl. Sci. 2024, 14(15), 6646; https://doi.org/10.3390/app14156646 - 30 Jul 2024

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Abstract

Background: An increasing number of people around the world suffer from Crohn’s disease (CD), one of the inflammatory bowel diseases (IBDs). Recent evidence suggests that the endogenous cannabinoid system plays an important role in IBD. The main endocannabinoids, anandamide (AEA) and 2-arachidonoylglycerol (2-AG), are ligands of the CB1 and CB2 receptors that are expressed on immune cells. These receptors as well as endocannabinoids are believed to mediate inflammatory activity and participate in the pathophysiology of CD. Objective: Very little is known about the secretion of endogenous cannabinoids throughout the course of CD. Therefore, the aim of this study was to determine and analyze the 2-AG and AEA concentrations in children who suffered from CD. Methods: We studied 34 adolescents with CD, mean age 13.5 years ± 2.0. Blood samples were collected three times in the active phase of the disease (during admission to hospital, before treatment), 2–4 weeks later, during the treatment and clinical improvement of the patients, and 3–6 months later, in the period of remission. The control group included 33 healthy teenagers of the same age who were examined once. In all patients, fasting blood samples were collected in the morning. 2AG and AEA concentrations in serum were measured using EIA kits (Abclonal, Woburn, MA, USA and ELK Biotechnology Co., Ltd. Wuhan, China, respectively). Results: The median 2-AG concentration in the study group was stable: acute phase 907.4 [379.3; 1300.5] pg/mL, during treatment 715.1 [416.7; 1302.5] pg/mL; remission 991.1 [381.1; 1652.5] pg/mL, and similar to the values observed in the control group 761.8 [504.3; 1497.0] pg/mL. No significant differences were found between the results obtained at all time points in the study group and compared to the control group (in all cases p > 0.44). In the case of AEA, in the study group before treatment, the median concentration was 2.63 [2.24; 2.79] ng/mL and similar to values obtained during treatment 2.56 [2.33; 3.06] ng/mL, and in remission, with 2.61 [2.46; 2.85] ng/mL. All these concentrations were lower compared to the values measured in the control group of 3.18 [2.57; 3.88] ng/mL (p = 0.023, p = 0.035, p = 0.056, respectively). Conclusions: While 2-AG levels remained stable throughout the disease course and were comparable to controls, AEA concentrations were consistently lower in CD patients. Therefore, therapeutic interventions aimed at increasing AEA-related signaling, such as administration of its analogues or fatty acid amide hydrolase inhibitors, may improve symptoms associated with Crohn’s disease in children. Full article

(This article belongs to the Special Issue 5th Anniversary of ‘Applied Biosciences and Bioengineering’ Section—Recent Advances in the Biochemistry of Inflammation)

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13 pages, 309 KiB

Open AccessArticle

Potential of Portuguese Viticulture By-Products as Natural Resources of Bioactive Compounds—Antioxidant and Antimicrobial Activities

by Ana F. Vinha, Carla Sousa, Andreia Vilela, Joana Ferreira, Rui Medeiros and Fátima Cerqueira

Appl. Sci. 2024, 14(14), 6278; https://doi.org/10.3390/app14146278 - 18 Jul 2024

Viewed by 1073

Abstract

Vitis vinifera is the grape variety used in the production of wine and other products. In the wine production process, many of the vine’s by-products are wasted, namely seeds and stems. Given the proportion of wine production worldwide, the quantity of by-products is beginning to be an environmental problem, making it urgent to take measures for their use to obtain bioactive compounds with health benefits. The aim of this work was to study the antioxidant and antimicrobial activities of extracts from the seeds and stems of four Portuguese grape varieties: Touriga Franca, Touriga Nacional, Viosinho, and Tinta Roriz. Total phenolic (TPC) and total flavonoids (TFC) contents present in the different extracts were evaluated, as well as the antioxidant activity, by DPPH and FRAP methods. TPC and TFC values of the stem’s extracts are much higher than those of the seeds of the same grape variety in the same solvent. The antioxidant activity of aqueous and ethanolic stem extracts is higher than that obtained for the seeds, showing that antioxidant activity is related to the content of polyphenols. The antimicrobial activity of different stem and seed extracts was determined against yeasts and Gram-positive and Gram-negative bacteria, and the effect was determined based on the minimal inhibitory concentrations calculated (MIC). In general, the ethanol:water (1:1) extract of the seeds from the different varieties tested inhibited C. albicans ATCC10231 and C. krusei ATCC6258 growth even at 200 μg/mL, and the effect was fungicidal at 200 μg/mL. The same type of extract showed selective antimicrobial activity, inhibiting S. aureus ATCC29213 growth but having no effect against E. coli ATCC25922 even at 200 μg/mL. The effect against S. aureus was bactericidal (at 200 μg/mL) for Touriga Franca, Touriga Nacional, and Viosinho. Taking all these results into account, it can be concluded that the by-products of the grape varieties tested are important sources of bioactive products, particularly as antioxidants and antimicrobials. Full article

(This article belongs to the Special Issue 5th Anniversary of ‘Applied Biosciences and Bioengineering’ Section—Recent Advances in the Biochemistry of Inflammation)

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29 pages, 1325 KiB

Open AccessReview

COVID-19 Lung Injury: Unique and Familiar Aspects of Pathophysiology

by Stefan Hall, Geraint Berger and Christian Lehmann

Appl. Sci. 2024, 14(23), 11048; https://doi.org/10.3390/app142311048 - 27 Nov 2024

Viewed by 2463

Abstract

Acute lung injury (ALI), diagnosed clinically as acute respiratory distress syndrome (ARDS), refers to a spectrum of acute inflammatory processes culminating in increased permeability of the pulmonary alveolar–capillary barrier and impaired gas exchange. The pandemic caused by the novel coronavirus, SARS-CoV-2, has raised questions as to the similarities and differences between COVID-19 lung injury and ALI of other etiologies. This review summarizes current knowledge regarding the pathophysiology of ALI and COVID-19 lung injury and draws comparisons between the latter and other infectious etiologies of ALI. Indeed, severe COVID-19 is characterized by a unique array of disease mechanisms including suppression of interferon responses, widespread inflammasome activation, altered leukocyte phenotypes, and hyperactive thrombotic activity. Moreover, these mechanisms manifest as a unique clinical progression, which further differentiates COVID-19 from other viral respiratory pathogens such as SARS, MERS, and influenza. These unique features of COVID-19 pathophysiology bear important implications for current and future therapeutic strategies. Full article

(This article belongs to the Special Issue 5th Anniversary of ‘Applied Biosciences and Bioengineering’ Section—Recent Advances in the Biochemistry of Inflammation)

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13 pages, 743 KiB

Open AccessReview

Tumor Microenvironment and Dermatological Conditions in Prostate Cancer

by Corina Daniela Ene, Cristina Capusa, Ilinca Nicolae, Mircea Tampa, Madalina Irina Mitran, Cristina Iulia Mitran, Claudia Ioana Dogaru, Andrei Marin, Ecaterina Rinja, Clara Matei and Simona Roxana Georgescu

Appl. Sci. 2024, 14(21), 9655; https://doi.org/10.3390/app14219655 - 22 Oct 2024

Viewed by 1463

Abstract

Tumor initiation, progression, and invasion are closely related to the tumor microenvironment. Inflammation can modulate the activity of the cells in the TME and contribute to all stages of tumor development. The etiopathogenesis of cutaneous manifestations associated with prostate cancer is unclear. The cutaneous phenotype associated with prostate cancer could be supported by intratumoral heterogeneity, the remodeling of interactions in the tumor microenvironment, and the dynamics of the epithelial–mesenchymal transition. Among the urinary system cancers, prostate cancer presents few cutaneous signs and symptoms, most being diagnosed in the advanced stages of the disease. In this review, we analyze the cutaneous events associated with prostate cancer, represented by direct or indirect manifestations of the primary malignancy and the skin toxicities caused by oncological medications. Full article

(This article belongs to the Special Issue 5th Anniversary of ‘Applied Biosciences and Bioengineering’ Section—Recent Advances in the Biochemistry of Inflammation)

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5th Anniversary of ‘Applied Biosciences and Bioengineering’ Section—Recent Advances in the Biochemistry of Inflammation

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