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Biomedicines
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Pathomechanisms of Disturbances Underlying Chronic Disorders—2nd Edition
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Pathomechanisms of Disturbances Underlying Chronic Disorders—2nd Edition

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Immunology and Immunotherapy".

Deadline for manuscript submissions: 30 April 2025 | Viewed by 11941

Special Issue Editor

Prof. Dr. Dorota Formanowicz

E-Mail Website
Guest Editor
Department of Medical Chemistry and Laboratory Medicine, Poznan University of Medical Sciences, Rokietnicka 8, 60-806 Poznan, Poland
Interests: chronic disorder; chronic kidney disease; obesity; cardiovascular disease
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Atherosclerosis and other chronic disorders remain a global problem. While we are witnessing tremendous progress in understanding their underlying mechanisms, our knowledge is still insufficient to prevent these complex diseases completely. Chronic diseases occur due to the interaction of many factors, the best example of which is atherosclerosis. Today we are far from convinced that classically understood lipids are to blame for everything. It is widely believed that atherosclerosis begins with a sequence of immune-inflammatory responses elicited in response to multifactorial damage to the endothelium. Despite lifestyle changes, the use of new drugs, the availability of new diagnostic tools and markers, and the implementation of new standards have significantly improved the epidemiological situation in the world over the last few decades, but chronic diseases remain a challenge for today's medicine.

In this Special Issue, research covering various aspects underlying chronic disorders are welcome. Interdisciplinary approaches are highly sought after. I look forward to receiving your contribution.

Dr. Dorota Formanowicz
Guest Editor

Manuscript Submission Information

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Keywords

  • chronic disorders
  • atherosclerosis
  • inflammation
  • oxidative stress
  • lipoproteins
  • endothelial dysfunction
  • biomarkers
  • pathomechanisms

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Published Papers (7 papers)

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Research

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14 pages, 3255 KiB  
Article
Relationships between Osteopontin, Osteoprotegerin, and Other Extracellular Matrix Proteins in Calcifying Arteries
by Aleksandra Kuzan, Agnieszka Chwiłkowska, Krzysztof Maksymowicz, Urszula Abramczyk and Andrzej Gamian
Biomedicines 2024, 12(4), 847; https://doi.org/10.3390/biomedicines12040847 - 11 Apr 2024
Cited by 1 | Viewed by 1201
Abstract
Osteopontin (OPN) and osteoprotegerin (OPG) are glycoproteins that participate in the regulation of tissue biomineralization. The aim of the project is to verify the hypothesis that the content of OPN and OPG in the aorta walls increases with the development of atherosclerosis and [...] Read more.
Osteopontin (OPN) and osteoprotegerin (OPG) are glycoproteins that participate in the regulation of tissue biomineralization. The aim of the project is to verify the hypothesis that the content of OPN and OPG in the aorta walls increases with the development of atherosclerosis and that these proteins are quantitatively related to the main proteins in the extracellular arteries matrix. Quantitative and qualitative analyses of the OPN and OPG content in 101 aorta sections have been conducted. Additionally, an enzyme-linked immunosorbent assay (ELISA) test has been performed to determine the collagen types I–IV and elastin content in the tissues. Correlations between the biochemical data and patients’ age/sex, atherosclerosis stages, and calcification occurrences in the tissue have been established. We are the first to report correlations between OPN or OPG and various types of collagen and elastin content (OPG/type I collagen correlation: r = 0.37, p = 0.004; OPG/type II collagen: r = 0.34, p = 0.007; OPG/type III collagen: r = 0.39, p = 0.002, OPG/type IV collagen: r = 0.27, p = 0.03; OPG/elastin: r = 0.42, p = 0.001; OPN/collagen type I: r = 0.34, p = 0.007; OPN/collagen type II: r = 0.52, p = 0.000; OPN/elastin: r = 0.61, p = 0.001). OPN overexpression accompanies calcium deposit (CA) formation with the protein localized in the calcium deposit, whereas OPG is located outside the CA. Although OPN and OPG seem to play a similar function (inhibiting calcification), these glycoproteins have different tissue localizations and independent expression regulation. The independent expression regulation presumably depends on the factors responsible for stimulating the synthesis of collagens and elastin. Full article
(This article belongs to the Special Issue Pathomechanisms of Disturbances Underlying Chronic Disorders—2nd Edition)
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19 pages, 623 KiB  
Article
Connections between Cognitive Impairment and Atrial Fibrillation in Patients with Diabetes Mellitus Type 2
by Marius Militaru, Daniel Florin Lighezan, Cristina Tudoran and Anda Gabriela Militaru
Biomedicines 2024, 12(3), 672; https://doi.org/10.3390/biomedicines12030672 - 17 Mar 2024
Cited by 4 | Viewed by 1234
Abstract
(1) Background: Cognitive decline (CD), considered a precursory state of dementia, is frequently encountered in patients with diabetes mellitus type 2 (DM-2) and might even have a higher prevalence in those with associated atrial fibrillation (AF). In this study, we aimed to research [...] Read more.
(1) Background: Cognitive decline (CD), considered a precursory state of dementia, is frequently encountered in patients with diabetes mellitus type 2 (DM-2) and might even have a higher prevalence in those with associated atrial fibrillation (AF). In this study, we aimed to research if the association of DM-2 and AF favors a precocious onset of CD. (2) Methods: This study was conducted on 160 patients, featuring 50 with DM-2, 54 with DM-2 and AF, and 56 subjects without DM-2 and AF, all evaluated clinically and with five neuropsychiatric scales. (3) Results: The Mini-Mental-State-Examination (MMSE), Montreal Cognitive Assessment (MoCA), Activities of Daily Living Score (ADL), Instrumental Activities of Daily Living Score (IADL), and Geriatric Depression Scale (GDS-15) were significantly altered in patients with DM-2 and AF in comparison to patients without these diseases. The logistic regression model indicated that, in patients with DM-2 and AF, an increase of one year in age is associated with a 7.3% augmentation of the risk of a precocious onset of CD (MMSE < 27). (4) Conclusions: CD is more frequent in patients with DM-2, especially when associated with AF, versus those without DM-2 and AF. Our findings suggest that an older age and associated dyslipidemia represent risk factors for CD in patients with DM-2. Full article
(This article belongs to the Special Issue Pathomechanisms of Disturbances Underlying Chronic Disorders—2nd Edition)
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13 pages, 1569 KiB  
Article
Urinary Viral Spectrum in Patients with Interstitial Cystitis/Bladder Pain Syndrome and the Clinical Efficacy of Valacyclovir Treatment
by Hann-Chorng Kuo, Chih-Wen Peng, Yuan-Hong Jiang and Jia-Fong Jhang
Biomedicines 2024, 12(3), 522; https://doi.org/10.3390/biomedicines12030522 - 26 Feb 2024
Cited by 1 | Viewed by 3525
Abstract
Our previous study showed that the Epstein–Barr virus (EBV) may be the etiology for some patients with interstitial cystitis/bladder pain syndrome (IC/BPS); hence, the current study aimed to investigate the urinary viral spectrum in patients with IC/BPS and the clinical efficacy of valacyclovir. [...] Read more.
Our previous study showed that the Epstein–Barr virus (EBV) may be the etiology for some patients with interstitial cystitis/bladder pain syndrome (IC/BPS); hence, the current study aimed to investigate the urinary viral spectrum in patients with IC/BPS and the clinical efficacy of valacyclovir. Twenty-eight patients were prospectively enrolled for valacyclovir 500 mg twice a day for 4 weeks. Urine samples were collected from IC/BPS patients and 30 controls. The primary outcome was the difference in the visual analog scale (VAS) pain score, and secondary outcomes included changes in the urinary viral spectrum and urinary inflammatory cytokine level (ClinicalTrials.gov Identifier: NCT05094414). Urinary EBV was detected in 14.2% IC/BPS patients but not in the controls. Urinary John Cunningham virus and BK virus were detected in 18 (64.3%) and 2 (7.1%) patients with IC/BPS, respectively, with similar prevalences noted for the controls. No cytomegalovirus, varicella-zoster virus, or herpes simplex virus was detected in the urine samples. The VAS pain score in patients with IC/BPS significantly decreased after 4 weeks (from 7.5 [5.52–9.0] to 5 [1.5–6.0], p = 0.0003). Urinary EBV was undetectable in any sample after valacyclovir treatment, and the decreases in urinary interleukin (IL)-1β (from 0.66 [0.55–0.82] pg/mL to 0.58 [0.55–0.64] pg/mL, p = 0.0034), IL-8 (from 6.81 [2.38 to 29.1] pg/mL to 4.33 [1.53–11.04] pg/mL, p = 0.0361), IL-10 (from 1.06 [0.94–1.18] pg/mL to 0.92 [0.88–1.02], p = 0.0086), and tumor necrosis factor-α (from 1.61 [1.50–1.72] pg/mL to 1.50 [1.44–1.55] pg/mL, p = 0.0079) were significant. Valacyclovir could relieve bladder pain, eliminate urinary EBV, and reduce bladder inflammation. Full article
(This article belongs to the Special Issue Pathomechanisms of Disturbances Underlying Chronic Disorders—2nd Edition)
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13 pages, 2006 KiB  
Article
Ribonucleic Acid Sequencing Reveals the Upregulation and Resolution of Inflammation and Extracellular Matrix Remodeling in Lidocaine-Treated Human Acute Monocytic Leukemia Cell Line THP-1
by Sheng-Wei Feng, Wei-Chun Lin, I-Ta Lee, Sheng-Dean Luo and Ching-Shuen Wang
Biomedicines 2024, 12(3), 509; https://doi.org/10.3390/biomedicines12030509 - 23 Feb 2024
Viewed by 1395
Abstract
Lidocaine, a local anesthetic widely used in dentistry, is esteemed for its efficacy and safety. Recent research reveals its additional role in modulating the immune system, and particularly in reducing inflammation crucial for protecting tooth-supporting tissues. Notably, monocytes and macrophages, essential cellular components [...] Read more.
Lidocaine, a local anesthetic widely used in dentistry, is esteemed for its efficacy and safety. Recent research reveals its additional role in modulating the immune system, and particularly in reducing inflammation crucial for protecting tooth-supporting tissues. Notably, monocytes and macrophages, essential cellular components overseeing various physiological and pathological processes, stand as potential mediators of lidocaine’s effects. Therefore, this study aimed to investigate how lidocaine influences cell behavior using RNA sequencing. To investigate the effect of lidocaine on THP-1 cells’ behavior, we performed an MTT assay and RNA-Seq along with qPCR analyses to evaluate the transcriptomic and proteomic changes in THP-1 cells. Our results showed that a high dose of lidocaine (>1 mM) had a significant cytotoxic effect on THP-1 cells. However, a lidocaine dose lower than 0.5 mM induced a mixed anti-inflammatory profile by significantly upregulating tissue remodeling (GDF15, FGF7, HGF, COL4A3, COL8A2, LAMB2, LAMC2, PDGFRA, and VEGFA) and through the resolution of inflammation (Cpeb4, Socs1, Socs2, Socs3, Dusp1, Tnfaip3, and Gata3) gene cassettes. This study explores the effect of lidocaine on the THP-1 in the M2-like healing phenotype and provides potential applications of lidocaine’s therapeutic effectiveness in dental tissue repair. Full article
(This article belongs to the Special Issue Pathomechanisms of Disturbances Underlying Chronic Disorders—2nd Edition)
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19 pages, 4761 KiB  
Article
Silica Nanoparticles Shed Light on Intriguing Cellular Pathways in Human Tracheal Smooth Muscle Cells: Revealing COX-2/PGE2 Production through the EGFR/Pyk2 Signaling Axis
by Wen-Bin Wu, I-Ta Lee, Yan-Jyun Lin, Ssu-Ying Wang, Li-Der Hsiao and Chuen-Mao Yang
Biomedicines 2024, 12(1), 107; https://doi.org/10.3390/biomedicines12010107 - 4 Jan 2024
Viewed by 1564
Abstract
The use of manufactured silica nanoparticles (SiNPs) has become widespread in everyday life, household products, and various industrial applications. While the harmful effects of crystalline silica on the lungs, known as silicosis or chronic pulmonary diseases, are well understood, the impact of SiNPs [...] Read more.
The use of manufactured silica nanoparticles (SiNPs) has become widespread in everyday life, household products, and various industrial applications. While the harmful effects of crystalline silica on the lungs, known as silicosis or chronic pulmonary diseases, are well understood, the impact of SiNPs on the airway is not fully explored. This study aimed to investigate the potential effects of SiNPs on human tracheal smooth muscle cells (HTSMCs). Our findings revealed that SiNPs induced the expression of cyclooxygenase-2 (COX-2) mRNA/protein and the production of prostaglandin E2 (PGE2) without causing cytotoxicity. This induction was transcription-dependent, as confirmed by cell viability assays and COX-2 luciferase reporter assays. Further analysis, including Western blot with pharmacological inhibitors and siRNA interference, showed the involvement of receptor tyrosine kinase (RTK) EGF receptor (EGFR), non-RTK Pyk2, protein kinase Cα (PKCα), and p42/p44 MAPK in the induction process. Notably, EGFR activation initiated cellular signaling that led to NF-κB p65 phosphorylation and translocation into the cell nucleus, where it bound and stimulated COX-2 gene transcription. The resulting COX-2 protein triggered PGE2 production and secretion into the extracellular space. Our study demonstrated that SiNPs mediate COX-2 up-regulation and PGE2 secretion in HTSMCs through the sequential activation of the EGFR/Pyk2/PKCα/p42/p44MAPKs-dependent NF-κB signaling pathway. Since PGE2 can have both physiological bronchodilatory and anti-inflammatory effects, as well as pathological pro-inflammatory effects, the increased PGE2 production in the airway might act as a protective compensatory mechanism and/or a contributing factor during airway exposure to SiNPs. Full article
(This article belongs to the Special Issue Pathomechanisms of Disturbances Underlying Chronic Disorders—2nd Edition)
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19 pages, 6388 KiB  
Article
Rhamnetin Prevents Bradykinin-Induced Expression of Matrix Metalloproteinase-9 in Rat Brain Astrocytes by Suppressing Protein Kinase-Dependent AP-1 Activation
by Chuen-Mao Yang, I-Ta Lee, Li-Der Hsiao, Zih-Yao Yu and Chien-Chung Yang
Biomedicines 2023, 11(12), 3198; https://doi.org/10.3390/biomedicines11123198 - 1 Dec 2023
Viewed by 1095
Abstract
Bradykinin (BK) has been recognized as a stimulant for matrix metalloproteinase (MMP)-9 expression, contributing to neuroinflammation. Modulating the BK/MMP-9 pathway offers potential in the treatment of neuroinflammatory disorders. Rhamnetin (RNT), a flavonoid compound known for its antioxidant and anti-inflammatory effects, has shown promise. [...] Read more.
Bradykinin (BK) has been recognized as a stimulant for matrix metalloproteinase (MMP)-9 expression, contributing to neuroinflammation. Modulating the BK/MMP-9 pathway offers potential in the treatment of neuroinflammatory disorders. Rhamnetin (RNT), a flavonoid compound known for its antioxidant and anti-inflammatory effects, has shown promise. However, the specific mechanisms through which RNT inhibits BK-induced MMP-9 expression remain unclear. Therefore, this study aims to delve into the intricate mechanisms underlying this process. Here, we initially demonstrated that RNT effectively attenuated BK-induced MMP-9 expression and its associated cell migration in rat brain astrocyte-1 (RBA-1) cells. Further investigation revealed that BK-driven MMP-9 protein, mRNA, and promoter activity linked to cell migration relied on c-Src, Pyk2, EGFR, PDGFR, PI3K/Akt, JNK1/2, and c-Jun. This was validated by the inhibition of these effects through specific inhibitors, a finding substantiated by the introduction of siRNAs targeting these signaling molecules. Notably, the phosphorylated levels of these signaling components induced by BK were significantly reduced by their respective inhibitors and RNT, underscoring the inhibitory role of RNT in this process. These findings indicate that, in RBA-1 cells, RNT diminishes the heightened induction of MMP-9 triggered by BK through the inhibition of c-Src/Pyk2/PDGFR and EGFR/PI3K/Akt/JNK1/2-dependent AP-1 activation. This suggests that RNT holds promise as a potential therapeutic approach for addressing neuroinflammation in the brain. Full article
(This article belongs to the Special Issue Pathomechanisms of Disturbances Underlying Chronic Disorders—2nd Edition)
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Review

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15 pages, 1235 KiB  
Review
The Pathomechanism and Current Treatments for Chronic Interstitial Cystitis and Bladder Pain Syndrome
by Wan-Ru Yu, Jia-Fong Jhang, Yuan-Hong Jiang and Hann-Chorng Kuo
Biomedicines 2024, 12(9), 2051; https://doi.org/10.3390/biomedicines12092051 - 10 Sep 2024
Viewed by 1237
Abstract
Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic and debilitating condition characterized by symptoms such as bladder pain, frequent urination, and nocturia. Pain is typically perceived in the lower abdomen, pelvic floor, or urethra, causing significant discomfort and impacting quality of life. Due [...] Read more.
Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic and debilitating condition characterized by symptoms such as bladder pain, frequent urination, and nocturia. Pain is typically perceived in the lower abdomen, pelvic floor, or urethra, causing significant discomfort and impacting quality of life. Due to the similarity of its symptoms with those of overactive bladder and acute bacterial cystitis, patients often face misdiagnosis and delayed appropriate treatment. Hunner’s (HIC) and non-Hunner’s IC (NHIC), each with distinct clinical presentations, urothelial dysfunction, chronic inflammation, and central sensitization and thus multimodal symptomatic treatment approaches, may be the most common pathogeneses of IC/BPS. Treatment of IC/BPS should involve identifying the different clinical phenotypes and underlying pathophysiology causing clinical symptoms and developing strategies tailored to the patient’s needs. This review discusses the roles of urine biomarkers, bladder inflammation, and glycosaminoglycans in the pathogenesis of IC/BPS. Various bladder treatment modalities are explored, including glycosaminoglycan replenishment, botulinum toxin A injection, platelet-rich plasma injection, low-energy shock waves, immunosuppression, and low-dose oral prednisolone. Pelvic floor muscle physiotherapy and bladder therapy combined with psychiatric consultation can help alleviate psychological stress and enhance the quality of life of patients with IC/BPS. Elucidating the pathological mechanisms and exploring diverse treatment options would help advance the care of individuals suffering from this challenging bladder condition. Full article
(This article belongs to the Special Issue Pathomechanisms of Disturbances Underlying Chronic Disorders—2nd Edition)
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