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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: 20 November 2023 | Viewed by 4490

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Dr. Ming-Ju Hsieh

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Oral Cancer Research Center, Changhua Christian Hospital, Changhua 500, Taiwan
Interests: apoptosis; autophagy; metastasis; anti-cancer; nature compound; cell biochemistry
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

More and more anti-cancer and anti-inflammatory active substances are being discovered and applied in treating cancer and inflammation. In this Special Issue, we are collecting papers regarding the role and molecular mechanisms of active substances in anti-inflammation and anti-cancer treatment. We welcome research articles and review papers focused on anti-cancer and anti-inflammatory active substances in cancer, from basic, translational science studies to clinical research.

This Special Issue is supervised by Dr. Ming-Ju Hsieh, and assisted by our Topical Advisory Panel Member, Dr. Sourav Ghorai (University of Illinois at Chicago).

Dr. Ming-Ju Hsieh
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

anti-inflammatory
anti-cancer
molecular mechanism
chemoresistance
molecular biology

Published Papers (7 papers)

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Research

Open AccessArticle

Medermycin Inhibits TNFα-Promoted Inflammatory Reaction in Human Synovial Fibroblasts

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Int. J. Mol. Sci. 2023, 24(18), 13871; https://doi.org/10.3390/ijms241813871 - 08 Sep 2023

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Abstract

Synovial inflammation plays a crucial role in the destruction of joints and the experience of pain in osteoarthritis (OA). Emerging evidence suggests that certain antibiotic agents and their derivatives possess anti-inflammatory properties. Medermycin (MED) has been identified as a potent antibiotic, specifically active against Gram-positive bacteria. In this study, we aimed to investigate the impact of MED on TNFα-induced inflammatory reactions in a synovial cell line, SW-982, as well as primary human synovial fibroblasts (HSF) using RNA sequencing, rtRT-PCR, ELISA, and western blotting. Through the analysis of differentially expressed genes (DEGs), we identified a total of 1478 significantly upregulated genes in SW-982 cells stimulated with TNFα compared to the vehicle control. Among these upregulated genes, MED treatment led to a reduction in 1167 genes, including those encoding proinflammatory cytokines such as IL1B, IL6, and IL8. Pathway analysis revealed the enrichment of DEGs in the TNF and NFκB signaling pathway, further supporting the involvement of MED in modulating inflammatory responses. Subsequent experiments demonstrated that MED inhibited the expression of IL6 and IL8 at both the mRNA and protein levels in both SW982 cells and HSF. Additionally, MED treatment resulted in a reduction in p65 phosphorylation in both cell types, indicating its inhibitory effect on NFκB activation. Interestingly, MED also inhibited Akt phosphorylation in SW982 cells, but not in HSF. Overall, our findings suggest that MED suppresses TNFα-mediated inflammatory cytokine production and p65 phosphorylation. These results highlight the potential therapeutic value of MED in managing inflammatory conditions in OA. Further investigations utilizing articular chondrocytes and animal models of OA may provide valuable insights into the therapeutic potential of MED for this disease. Full article

(This article belongs to the Special Issue Latest Research on Anti-cancer, Anti-inflammatory, and Antioxidation Active Substances)

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Open AccessArticle

Picrasidine J, a Dimeric β-Carboline-Type Alkaloid from Picrasma quassioides, Inhibits Metastasis of Head and Neck Squamous Cell Carcinoma

Mosleh Mohammad Abomughaid

and

Ming-Ju Hsieh

Int. J. Mol. Sci. 2023, 24(17), 13230; https://doi.org/10.3390/ijms241713230 - 25 Aug 2023

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Abstract

Head and neck squamous cell carcinoma (HNSCC) are associated with recurrence, distant metastasis, and poor overall survival. This highlights the need for identifying potential therapeutics with minimal side-effects. The present study was designed to investigate the anticancer effects of picrasidine J, a dimeric β-carboline-type alkaloid isolated from the southern Asian plant Picrasma quassioides. The results showed that picrasidine J significantly inhibits HNSCC cell motility, migration, and invasion. Specifically, picrasidine J inhibited the EMT process by upregulating E-cadherin and ZO-1 and downregulating beta-catenin and Snail. Moreover, picrasidine J reduced the expression of the serine protease KLK-10. At the signaling level, the compound reduced the phosphorylation of ERK. All these factors collectively facilitated the inhibition of HNSCC metastasis with picrasidine J. Taken together, the study identifies picrasidine J as a potential anticancer compound of plant origin that might be used clinically to prevent the distant metastasis and progression of HNSCC. Full article

(This article belongs to the Special Issue Latest Research on Anti-cancer, Anti-inflammatory, and Antioxidation Active Substances)

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Open AccessArticle

A Novel Multi-Component Formulation Reduces Inflammation In Vitro and Clinically Lessens the Symptoms of Chronic Eczematous Skin

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Int. J. Mol. Sci. 2023, 24(16), 12979; https://doi.org/10.3390/ijms241612979 - 19 Aug 2023

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Abstract

Long-term treatments for inflammatory skin diseases like atopic dermatitis or eczema can cause adverse effects. Super Protein Multifunction (SPM) was investigated as a potential treatment for managing skin inflammation by monitoring the expression of pro-inflammatory cytokines induced using LPS and poly(I:C)/TNFα in HaCaT keratinocytes and Hs27 fibroblasts as measured via RT-PCR. SPM solution was also assessed for its effect on cytokine release, measured using ELISA, in a UVB-irradiated 3D human skin model. To evaluate the efficiency of SPM, 20 patients with mild eczematous skin were randomized to receive SPM or vehicle twice a day for three weeks in a double-blind controlled trial. In vitro studies showed SPM inhibited inflammation-induced IL-1β, IL-6, IL-33, IL-1α, TSLP, and TNFα expression or release. In the clinical study, the SPM group showed significant improvements in the IGA, PA, and DLQI scores compared to the vehicle group. Neither group showed significant differences in VAS (pruritus). Histological analysis showed reduced stratum corneum thickness and inflammatory cell infiltration. The results suggest that SPM may reduce inflammation in individuals with chronic eczematous skin. Full article

(This article belongs to the Special Issue Latest Research on Anti-cancer, Anti-inflammatory, and Antioxidation Active Substances)

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Open AccessArticle

A Comparative Analysis of Chemical Constituents and Antioxidant Effects of Dendrobium fimbriatum Hook Fractions with Different Polarities

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Int. J. Mol. Sci. 2023, 24(16), 12646; https://doi.org/10.3390/ijms241612646 - 10 Aug 2023

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Abstract

The aim of this study was to investigate the chemical composition and antioxidant capacity of various polar fractions obtained from Dendrobium fimbriatum Hook (DH). First, a 90% ethanol-aqueous extract of DH (CF) was subjected to sequential fractionation using different organic solvents, resulting in the isolation of a methylene chloride fraction (DF), an ethyl acetate fraction (EF), an n-butanol fraction (BF), and a remaining water fraction (WF) after condensation. Additionally, the CF was also subjected to column chromatography via a D101 macroreticular resin column, eluted with ethanol-aqueous solution to yield six fractions (0%, 20%, 40%, 60%, 80%, and 100%). UPLC-Q-Exactive Orbitrap-MS/MS analysis identified a total of 47 chemical compounds from these polar fractions, including fatty acids, amino acids, phenolic acids, flavonoids, organic heterocyclic molecules, and aromatic compounds. Moreover, DF, EF, and the 60%, 80%, and 100% ethanol-aqueous fractions had higher total phenol content (TPC) and total flavonoid content (TFC) values and greater 2,2′-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS-) and 1,1-diphenyl-2-picrylhydrazyl (DPPH)-scavenging abilities. In H₂O₂-induced HepG2 cells, the aforementioned fractions could increase the activities of antioxidative enzymes NAD(P)H: quinone oxidoreductase 1 (NQO1), superoxide dismutase (SOD), heme oxygenase-1 (HO-1) and catalase (CAT), stimulate glutathione (GSH) synthesis by increasing the activities of glutamic acid cysteine ligase (GCL) and glutathione synthetase (GS), regulate GSH metabolism by increasing glutathione peroxidase (GSH-Px) and glutathione reductase (GR) activities, and reduce levels of reactive oxygen species (ROS) and malondialdehyde (MDA). Furthermore, the antioxidative stress effect of the DH fractions was found to be positively correlated with the activation of nuclear factor-erythroid 2-related factor 2 (Nrf2) protein and the presence of antioxidative chemical constituents. In conclusion, this study highlights the efficacy of both liquid–liquid extraction and macroporous resin purification techniques in the enrichment of bioactive compounds from natural food resources. The comprehensive analysis of chemical constituents and antioxidant effects of different polar fractions from Dendrobium fimbriatum Hook contributes to the understanding of its potential application in functional foods and nutraceuticals. Full article

(This article belongs to the Special Issue Latest Research on Anti-cancer, Anti-inflammatory, and Antioxidation Active Substances)

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Open AccessArticle

Magnetic Nanoemulsions for the Intra-Articular Delivery of Ascorbic Acid and Dexamethasone

Camelia Mihaela Zară-Dănceanu

Răzvan-Nicolae Malancus

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Int. J. Mol. Sci. 2023, 24(15), 11916; https://doi.org/10.3390/ijms241511916 - 25 Jul 2023

Viewed by 707

Abstract

(1) Osteoarthritis (OA) is a progressive joint degenerative disease that currently has no cure. Limitations in the development of innovative disease modifying therapies are related to the complexity of the underlying pathogenic mechanisms. In addition, there is the unmet need for efficient drug delivery methods. Magnetic nanoparticles (MNPs) have been proposed as an efficient modality for the delivery of bioactive molecules within OA joints, limiting the side effects associated with systemic delivery. We previously demonstrated MNP’s role in increasing cell proliferation and chondrogenesis. In the design of intra-articular therapies for OA, the combined NE-MNP delivery system could provide increased stability and biological effect. (2) Proprietary Fe₃O₄ MNPs formulated as oil-in-water (O/W) magneto nanoemulsions (MNEs) containing ascorbic acid and dexamethasone were tested for size, stability, magnetic properties, and in vitro biocompatibility with human primary adipose mesenchymal cells (ADSC), cell mobility, and chondrogenesis. In vivo biocompatibility was tested after systemic administration in mice. (3) We report high MNE colloidal stability, magnetic properties, and excellent in vitro and in vivo biocompatibility. By increasing ADSC migration potential and chondrogenesis, MNE carrying dexamethasone and ascorbic acid could reduce OA symptoms while protecting the cartilage layer. Full article

(This article belongs to the Special Issue Latest Research on Anti-cancer, Anti-inflammatory, and Antioxidation Active Substances)

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Open AccessArticle

Antioxidant Chimeric Molecules: Are Chemical Motifs Additive? The Case of a Selenium-Based Ligand

Davide Zeppilli

Anna Aldinio-Colbachini

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Int. J. Mol. Sci. 2023, 24(14), 11797; https://doi.org/10.3390/ijms241411797 - 22 Jul 2023

Viewed by 421

Abstract

We set up an in silico experiment and designed a chimeric compound integrating molecular features from different efficient ROS (Reactive Oxygen Species) scavengers, with the purpose of investigating potential relationships between molecular structure and antioxidant activity. Furthermore, a selenium centre was inserted due to its known capacity to reduce hydroperoxides, acting as a molecular mimic of glutathione peroxidase; finally, since this organoselenide is a precursor of a N-heterocyclic carbene ligand, its Au(I) carbene complex was designed and examined. A validated protocol based on DFT (Density Functional Theory) was employed to investigate the radical scavenging activity of available sites on the organoselenide precursor ((SMD)-M06-2X/6-311+G(d,p)//M06-2X/6-31G(d)), as well as on the organometallic complex ((SMD)-M06-2X/SDD (Au), 6-311+G(d,p)//ZORA-BLYP-D3(BJ)/TZ2P), considering HAT (Hydrogen Atom Transfer) and RAF (Radical Adduct Formation) regarding five different radicals. The results of this case study suggest that the antioxidant potential of chemical motifs should not be considered as an additive property when designing a chimeric compound, but rather that the relevance of a molecular topology is derived from a chemical motif combined with an opportune chemical space of the molecule. Thus, the direct contributions of single functional groups which are generally thought of as antioxidants per se do not guarantee the efficient radical scavenging potential of a molecular species. Full article

(This article belongs to the Special Issue Latest Research on Anti-cancer, Anti-inflammatory, and Antioxidation Active Substances)

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Open AccessArticle

Synthesis and Anti-Proliferative Activity of 5-Benzoyl and 5-Benzylhydroxy Derivatives of 3-Amino-2-Arylcarboxamido-Thieno[2-3-b]Pyridines

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Int. J. Mol. Sci. 2023, 24(14), 11407; https://doi.org/10.3390/ijms241411407 - 13 Jul 2023

Viewed by 562

Abstract

3-Amino-2-arylcarboxamido-thieno[2-3-b]pyridines have been previously described as having potent anti-proliferative activity against MDA-MB-231 and HCT116 cancer cell lines. The mechanism by which these molecules prevent cancer cell growth is proposed to be through interfering with phospholipid metabolism via inhibition of PI-PLC, along with other cellular processes. Previously, 5-cinnamyl derivatives of these thieno[2-3-b]pyridines have been shown to have enhanced anti-proliferative activity compared to compounds lacking this moiety, indicating a tethered aromatic ring is important for this western region of the pharmacophore. Herein, we report the synthesis and biological evaluation of a library of 40 novel thieno[2-3-b]pyridine analogues containing shorter benzoyl or secondary benzyl alcohol tethers at the 5-position, in addition to various substituents on the two phenyl rings present on the molecule. Compounds bearing alcohol functionality had improved efficacy compared to their benzoyl counterparts, in addition to a 2-methyl-3-halogen substitution on the 2-arylcarboxamide ring being important for maximising anti-proliferative activity. The most potent molecules 7h and 7i demonstrated IC₅₀ concentrations of 25–50 nM against HCT116 and MDA-MB-231 cells, a similar level of activity as previous thienopyridine compounds bearing cinnamyl moieties, suggesting that these novel derivatives with shorter tethers were able to maintain potent anti-proliferative activity, while allowing for a more concise synthesis. Full article

(This article belongs to the Special Issue Latest Research on Anti-cancer, Anti-inflammatory, and Antioxidation Active Substances)

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Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Planned Paper I: Synthesis and anti-proliferative activity of 5-benzoyl derivatives of 3-amino-2-arylcarboxamido-thieno[2-3-b]pyridines-Prof. David Barker

Planned Paper II: Immunogenic cancer cell death by repurposed compounds and standard therapies: Implications on efficacy of immunotherapy-Dr. Shreyas Gaikwad

Planned Paper IV: The role of magnetoliposomes loaded with dexamethasone and ascorbic acid in condrogenesis-Dr. Camelia Danceanu & Dr. Labusca

Planned Paper V: Lipid based nanoparticles as drug delivery carries for cancer therapy-Dr. Anwar Ali

Planned Paper VI: Magnolol alleviates atopic dermatitis-like symptoms in BALB/c mice-Dr. Dong-Soon Im

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