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Chronic Inflammation and Related Diseases: From Mechanisms to Therapies 2.0
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Chronic Inflammation and Related Diseases: From Mechanisms to Therapies 2.0

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (31 May 2023) | Viewed by 19206

Special Issue Editor

Dr. Suk-Yun Kang

E-Mail Website
Guest Editor
KM Science Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, Republic of Korea
Interests: inflammatory pain; mechanisms of pain; alternative medicine; central sensitization
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue is the continuation of our previous Special Issue, “Chronic Inflammation and Related Diseases: From Mechanisms to Therapies”.

Inflammation is a defense response of the living body to harmful stimuli, for example pathogens or injuries. Inflammation removes the cause of cell damage and goes through the steps of removing dead cells and tissues due to injury and inflammatory response, and then it goes through the stage of initial repair, which restores cells or tissues to their original state. Chronic inflammation has a longer course than acute inflammation, and the causes of it are complex and involve the severity of tissue disorders, repetition of inflammatory stimuli, and the reactivity of the body. There are five typical signs: fever, pain, redness, swelling and loss of function. Inflammatory pain is especially characterized by increased sensitivity due to the inflammatory response associated with tissue damage, resulting in increased activity of primary afferent nerves, resulting in spontaneous pain, hyperalgesia, and allodynia.

Therefore, detailed research is needed to elucidate the exact mechanism for more effective inflammation management and development of anti-inflammatory and analgesic treatment methods for inflammatory pain patients.

The purpose of this Special Issue is to bring together experts in the field of inflammation and pain to investigate precise molecular mechanisms. This Special Issue welcomes original research and review articles.

Dr. Suk-Yun Kang
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.

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Keywords

  • inflammation
  • inflammatory pain
  • molecular mechanism
  • central sensitization

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Published Papers (6 papers)

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Research

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10 pages, 1512 KiB  
Article
Protective Effects of Cirsilineol against Lipopolysaccharide-Induced Inflammation; Insights into HO-1, COX-2, and iNOS Modulation
by Go Oun Kim, Dong Ho Park and Jong-Sup Bae
Int. J. Mol. Sci. 2023, 24(10), 8537; https://doi.org/10.3390/ijms24108537 - 10 May 2023
Cited by 4 | Viewed by 1632
Abstract
In this study, the potential protective effects of cirsilineol (CSL), a natural compound found in Artemisia vestita, were examined on lipopolysaccharide (LPS)-induced inflammatory responses. CSL was found to have antioxidant, anticancer, and antibacterial properties, and was lethal to many cancer cells. We [...] Read more.
In this study, the potential protective effects of cirsilineol (CSL), a natural compound found in Artemisia vestita, were examined on lipopolysaccharide (LPS)-induced inflammatory responses. CSL was found to have antioxidant, anticancer, and antibacterial properties, and was lethal to many cancer cells. We assessed the effects of CSL on heme oxygenase (HO)-1, cyclooxygenase (COX)-2, and inducible nitric oxide synthase (iNOS) in LPS-activated human umbilical vein endothelial cells (HUVECs). We also examined the effects of CSL on the expression of iNOS, tumor necrosis factor (TNF)-α, and interleukin (IL)-1β in the pulmonary histological status of LPS-injected mice. The results showed that CSL increased HO-1 production, inhibited luciferase-NF-κB interaction, and reduced COX-2/PGE2 and iNOS/NO levels, leading to a decrease in signal transducer and activator of transcription (STAT)-1 phosphorylation. CSL also enhanced the nuclear translocation of Nrf2, elevated the binding activity between Nrf2 and antioxidant response elements (AREs), and reduced IL-1β expression in LPS-treated HUVECs. We found that CSL’s suppression of iNOS/NO synthesis was restored by inhibiting HO-1 through RNAi. In the animal model, CSL significantly decreased iNOS expression in the pulmonary biostructure, and TNF-α level in the bronchoalveolar lavage fluid. These findings indicate that CSL has anti-inflammatory properties by controlling iNOS through inhibition of both NF-κB expression and p-STAT-1. Therefore, CSL may have potential as a candidate for developing new clinical substances to treat pathological inflammation. Full article
(This article belongs to the Special Issue Chronic Inflammation and Related Diseases: From Mechanisms to Therapies 2.0)
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12 pages, 1550 KiB  
Article
7,8-Dihydroxyflavone Attenuates Inflammatory Response and Insulin Resistance Induced by the Paracrine Interaction between Adipocytes and Macrophages
by Ye-Eun Shin, Ji Won Choi, Yong Il Park and Hye-Kyeong Kim
Int. J. Mol. Sci. 2023, 24(4), 3520; https://doi.org/10.3390/ijms24043520 - 9 Feb 2023
Cited by 5 | Viewed by 1955
Abstract
Obesity-induced inflammation and insulin resistance are mediated by macrophage infiltration into adipose tissue. We investigated the effects of 7,8-dihydroxyflavone (7,8-DHF), a flavone found in plants, on the inflammatory response and insulin resistance induced by the interaction between adipocytes and macrophages. Hypertrophied 3T3-L1 adipocytes [...] Read more.
Obesity-induced inflammation and insulin resistance are mediated by macrophage infiltration into adipose tissue. We investigated the effects of 7,8-dihydroxyflavone (7,8-DHF), a flavone found in plants, on the inflammatory response and insulin resistance induced by the interaction between adipocytes and macrophages. Hypertrophied 3T3-L1 adipocytes were cocultured with RAW 264.7 macrophages and treated with 7,8-DHF (3.12, 12.5, and 50 μM). The inflammatory cytokines and free fatty acid (FFA) release were evaluated by assay kits, and signaling pathways were determined by immunoblotting. Coculture of adipocytes and macrophages increased inflammatory mediators, such as nitric oxide (NO), monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) and FFA secretion but suppressed the production of anti-inflammatory adiponectin. 7,8-DHF counteracted the coculture-induced changes (p < 0.001). 7,8-DHF also inhibited c-Jun N-terminal kinase (JNK) activation and blocked nuclear factor kappa B (NF-κB) nuclear translocation in the coculture system (p < 0.01). In addition, adipocytes cocultured with macrophages did not increase glucose uptake and Akt phosphorylation in response to insulin. However, 7,8-DHF treatment recovered the impaired responsiveness to insulin (p < 0.01). These findings show that 7,8-DHF alleviates inflammation and adipocyte dysfunction in the coculture of hypertrophied 3T3-L1 adipocytes and RAW 264.7 macrophages, indicating its potential as a therapeutic agent for obesity-induced insulin resistance. Full article
(This article belongs to the Special Issue Chronic Inflammation and Related Diseases: From Mechanisms to Therapies 2.0)
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14 pages, 3777 KiB  
Article
Pulsed Electromagnetic Field (PEMF) Treatment Ameliorates Murine Model of Collagen-Induced Arthritis
by Ju-Eun Hong, Chang-Gun Lee, Soonjae Hwang, Junyoung Kim, Minjeong Jo, Da-Hye Kang, Sang-Hyeon Yoo, Woo-Seung Kim, Yongheum Lee and Ki-Jong Rhee
Int. J. Mol. Sci. 2023, 24(2), 1137; https://doi.org/10.3390/ijms24021137 - 6 Jan 2023
Cited by 8 | Viewed by 6369
Abstract
Rheumatoid arthritis (RA) is an autoimmune disease of the joint synovial membranes. RA is difficult to prevent or treat; however, blocking proinflammatory cytokines is a general therapeutic strategy. Pulsed electromagnetic field (PEMF) is reported to alleviate RA’s inflammatory response and is being studied [...] Read more.
Rheumatoid arthritis (RA) is an autoimmune disease of the joint synovial membranes. RA is difficult to prevent or treat; however, blocking proinflammatory cytokines is a general therapeutic strategy. Pulsed electromagnetic field (PEMF) is reported to alleviate RA’s inflammatory response and is being studied as a non-invasive physical therapy. In this current study, PEMF decreased paw inflammation in a collagen-induced arthritis (CIA) murine model. PEMF treatment at 10 Hz was more effective in ameliorating arthritis than at 75 Hz. In the PEMF-treated CIA group, the gross inflammation score and cartilage destruction were lower than in the untreated CIA group. The CIA group treated with PEMF also showed lower serum levels of IL-1β but not IL-6, IL-17, or TNF-α. Serum levels of total anti-type II collagen IgG and IgG subclasses (IgG1, IgG2a, and IgG2b) remained unchanged. In contrast, tissue protein levels of IL-1β, IL-6, TNF-α, receptor activator of nuclear factor kappa-Β (RANK), RANK ligand (RANKL), IL-6 receptor (IL-6R), and TNF-α receptor1 (TNFR1) were all lower in the ankle joints of the PEMF-treated CIA group compared with the CIA group. The results of this study suggest that PEMF treatment can preserve joint morphology cartilage and delay the occurrence of CIA. PEMF has potential as an effective adjuvant therapy that can suppress the progression of RA. Full article
(This article belongs to the Special Issue Chronic Inflammation and Related Diseases: From Mechanisms to Therapies 2.0)
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Review

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26 pages, 1572 KiB  
Review
Type 2 Diabetes Mellitus, Non-Alcoholic Fatty Liver Disease, and Metabolic Repercussions: The Vicious Cycle and Its Interplay with Inflammation
by Rafał Frankowski, Mateusz Kobierecki, Andrzej Wittczak, Monika Różycka-Kosmalska, Tadeusz Pietras, Kasper Sipowicz and Marcin Kosmalski
Int. J. Mol. Sci. 2023, 24(11), 9677; https://doi.org/10.3390/ijms24119677 - 2 Jun 2023
Cited by 7 | Viewed by 3607
Abstract
The prevalence of metabolic-related disorders, such as non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (DM2), has been increasing. Therefore, developing improved methods for the prevention, treatment, and detection of these two conditions is also necessary. In this study, our primary [...] Read more.
The prevalence of metabolic-related disorders, such as non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (DM2), has been increasing. Therefore, developing improved methods for the prevention, treatment, and detection of these two conditions is also necessary. In this study, our primary focus was on examining the role of chronic inflammation as a potential link in the pathogenesis of these diseases and their interconnections. A comprehensive search of the PubMed database using keywords such as “non-alcoholic fatty liver disease”, “type 2 diabetes mellitus”, “chronic inflammation”, “pathogenesis”, and “progression” yielded 177 relevant papers for our analysis. The findings of our study revealed intricate relationships between the pathogenesis of NAFLD and DM2, emphasizing the crucial role of inflammatory processes. These connections involve various molecular functions, including altered signaling pathways, patterns of gene methylation, the expression of related peptides, and up- and downregulation of several genes. Our study is a foundational platform for future research into the intricate relationship between NAFLD and DM2, allowing for a better understanding of the underlying mechanisms and the potential for introducing new treatment standards. Full article
(This article belongs to the Special Issue Chronic Inflammation and Related Diseases: From Mechanisms to Therapies 2.0)
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14 pages, 1821 KiB  
Review
Potential of Interleukin (IL)-12 Group as Antivirals: Severe Viral Disease Prevention and Management
by Nur Azizah A. Rahman, Vinod R. M. T. Balasubramaniam and Wei Boon Yap
Int. J. Mol. Sci. 2023, 24(8), 7350; https://doi.org/10.3390/ijms24087350 - 16 Apr 2023
Cited by 5 | Viewed by 2210
Abstract
The interleukin (IL)-12 family consists of pro- and anti-inflammatory cytokines that are able to signal the activation of host antiviral immunity while preventing over-reactive immune reactions due to active virus replication and viral clearance. Amongst others, IL-12 and IL-23 are produced and released [...] Read more.
The interleukin (IL)-12 family consists of pro- and anti-inflammatory cytokines that are able to signal the activation of host antiviral immunity while preventing over-reactive immune reactions due to active virus replication and viral clearance. Amongst others, IL-12 and IL-23 are produced and released by innate immune cells such as monocytes and macrophages to signal the proliferation of T cells and release of effector cytokines, which subsequently activate host defence against virus infections. Interestingly, the dualities of IL-27 and -35 are evidently shown in the course of virus infections; they regulate the synthesis of cytokines and antiviral molecules, proliferation of T cells, and viral antigen presentation in order to maximize virus clearance by the host immune system. In terms of anti-inflammatory reactions, IL-27 signals the formation of regulatory T cells (Treg) which in turn secrete IL-35 to control the scale of inflammatory response that takes place during virus infections. Given the multitasking of the IL-12 family in regards to the elimination of virus infections, its potential in antiviral therapy is unequivocally important. Thus, this work aims to delve deeper into the antiviral actions of the IL-12 family and their applications in antiviral therapies. Full article
(This article belongs to the Special Issue Chronic Inflammation and Related Diseases: From Mechanisms to Therapies 2.0)
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Other

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16 pages, 3246 KiB  
Brief Report
Anti-Obesity and Anti-Inflammatory Synergistic Effects of Green Tea Catechins and Citrus β-Cryptoxanthin Ingestion in Obese Mice
by Kazuhiko Nakadate, Kiyoharu Kawakami and Noriko Yamazaki
Int. J. Mol. Sci. 2023, 24(8), 7054; https://doi.org/10.3390/ijms24087054 - 11 Apr 2023
Cited by 11 | Viewed by 2761
Abstract
Chronic obesity causes various diseases, leading to an urgent need for its treatment and prevention. Using monosodium-glutamate-induced obesity mice, the present study investigated the synergistic obesity-reducing effects of tea catechins and the antioxidant β-cryptoxanthin present in mandarin oranges. The results show that the [...] Read more.
Chronic obesity causes various diseases, leading to an urgent need for its treatment and prevention. Using monosodium-glutamate-induced obesity mice, the present study investigated the synergistic obesity-reducing effects of tea catechins and the antioxidant β-cryptoxanthin present in mandarin oranges. The results show that the obese mice that ingested both tea catechin and β-cryptoxanthin for 4 weeks had a significantly decreased body weight, with no difference in body weight compared with control mice. Moreover, the blood biochemical test results were normal, and the body fat percentage was significantly decreased according to the histopathological analysis. Additionally, the abundance of M1 macrophages, which release pro-inflammatories, was significantly reduced in adipose tissue. Indeed, a significant decrease was detected in M1-macrophage-secreted tumor necrosis factor-alpha levels. Meanwhile, M2 macrophage levels were recovered, and adiponectin, which is released from adipocytes and involved in suppressing metabolic syndrome, was increased. Collectively, these results suggest that the combination of tea catechins and antioxidant foods can alleviate chronic obesity, indicating that a combination of various ingredients in foods might contribute to reducing chronic obesity. Full article
(This article belongs to the Special Issue Chronic Inflammation and Related Diseases: From Mechanisms to Therapies 2.0)
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