Biomedicines

Editorial

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5 pages, 189 KiB

Open AccessEditorial

Pathomechanisms of Disturbances Underlying Chronic Disorders

by Dorota Formanowicz

Biomedicines 2024, 12(1), 131; https://doi.org/10.3390/biomedicines12010131 - 09 Jan 2024

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Abstract

Chronic disorders’ complexity poses enormous challenges to our understanding of such disorders [...] Full article

(This article belongs to the Special Issue Pathomechanisms of Disturbances Underlying Chronic Disorders)

Research

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29 pages, 6560 KiB

Open AccessArticle

Holistic View on the Structure of Immune Response: Petri Net Model

by Sonja Scharf, Jörg Ackermann, Leonie Bender, Patrick Wurzel, Hendrik Schäfer, Martin-Leo Hansmann and Ina Koch

Biomedicines 2023, 11(2), 452; https://doi.org/10.3390/biomedicines11020452 - 04 Feb 2023

Cited by 3 | Viewed by 1367

Abstract

The simulation of immune response is a challenging task because quantitative data are scarce. Quantitative theoretical models either focus on specific cell–cell interactions or have to make assumptions about parameters. The broad variation of, e.g., the dimensions and abundance between lymph nodes as [...] Read more.

The simulation of immune response is a challenging task because quantitative data are scarce. Quantitative theoretical models either focus on specific cell–cell interactions or have to make assumptions about parameters. The broad variation of, e.g., the dimensions and abundance between lymph nodes as well as between individual patients hampers conclusive quantitative modeling. No theoretical model has been established representing a consensus on the set of major cellular processes involved in the immune response. In this paper, we apply the Petri net formalism to construct a semi-quantitative mathematical model of the lymph nodes. The model covers the major cellular processes of immune response and fulfills the formal requirements of Petri net models. The intention is to develop a model taking into account the viewpoints of experienced pathologists and computer scientists in the field of systems biology. In order to verify formal requirements, we discuss invariant properties and apply the asynchronous firing rule of a place/transition net. Twenty-five transition invariants cover the model, and each is assigned to a functional mode of the immune response. In simulations, the Petri net model describes the dynamic modes of the immune response, its adaption to antigens, and its loss of memory. Full article

(This article belongs to the Special Issue Pathomechanisms of Disturbances Underlying Chronic Disorders)

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12 pages, 1094 KiB

Open AccessArticle

Ghrelin and Leptin among Patients with Urolithiasis with Concomitant Hyperuricemia and Metabolic Syndrome

by Michalina Lubawy, Anna Blacha, Marcin Nowicki, Tomasz Deja, Krzysztof Wałkowski and Dorota Formanowicz

Biomedicines 2023, 11(2), 285; https://doi.org/10.3390/biomedicines11020285 - 19 Jan 2023

Cited by 3 | Viewed by 1232

Abstract

Introduction: The study evaluated the selected appetite hormones (ghrelin, leptin) and inflammatory parameters (tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6)) in patients with urolithiasis, metabolic syndrome (MetS), and hyperuricemia. Materials: 57 patients with urolithiasis, MetS and hyperuricemia (UP group) and [...] Read more.

Introduction: The study evaluated the selected appetite hormones (ghrelin, leptin) and inflammatory parameters (tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6)) in patients with urolithiasis, metabolic syndrome (MetS), and hyperuricemia. Materials: 57 patients with urolithiasis, MetS and hyperuricemia (UP group) and 29 healthy people as the control group (CG group) were recruited to the study. All persons were 22–60 age. Methods: After preliminary testing, the qualified participants were evaluated for fasting serum levels of ghrelin, leptin, IL-6, and TNF-α. Results: Our results revealed differences between average values of leptin (p = 0.045), ghrelin (p < 0.001), IL-6 (p < 0.001), and TNF-α (p < 0.001) in the studied groups. Moreover, in the UP group, significant correlations were found between ghrelin and leptin; between these hormones and IL-6, and between leptin and uric acid (UA). Besides, leptin concentration increased significantly along with the changes in the body mass index (BMI) categories in the UP group. Conclusions: This study showed that patients with urolithiasis, concomitant MetS, and high UA levels may have problems managing appetite hormones. Full article

(This article belongs to the Special Issue Pathomechanisms of Disturbances Underlying Chronic Disorders)

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9 pages, 1225 KiB

Open AccessArticle

Hyperlipoproteinemia(a) and Severe Coronary Artery Lesion Types

by Larisa N. Ilina, Olga I. Afanasieva, Andrey A. Shiryaev, Elina E. Vlasova, Said K. Kurbanov, Marina I. Afanasieva, Marat V. Ezhov, Vladislav P. Vasiliev, Damir M. Galyautdinov, Sergey N. Pokrovsky and Renat S. Akchurin

Biomedicines 2022, 10(11), 2848; https://doi.org/10.3390/biomedicines10112848 - 08 Nov 2022

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Abstract

Diffuse atherosclerosis and calcification of the coronary arteries (CA) create serious difficulties for coronary artery bypass grafting (CABG). The aim of this study was to compare demographic indicators, lipids, and clinical results one year after CABG in patients with different phenotypes of coronary [...] Read more.

Diffuse atherosclerosis and calcification of the coronary arteries (CA) create serious difficulties for coronary artery bypass grafting (CABG). The aim of this study was to compare demographic indicators, lipids, and clinical results one year after CABG in patients with different phenotypes of coronary artery (CA) disease. In total, 390 patients hospitalized for elective CABG were included in a single-center prospective study. Demographic data, lipids (total, low-density lipoprotein and high-density lipoprotein cholesterol, and triglycerides), and lipoprotein(a) (Lp(a)) concentrations were analyzed for all patients. Major adverse cardiovascular events (MACE) included myocardial infarction, stroke, percutaneous coronary intervention, and death from cardiac causes within one year after surgery. No significant outcome differences were found between the groups with diffuse vs. segmental lesions, nor the groups with and without calcinosis for all studied parameters except for Lp(a). Median Lp(a) concentrations were higher in the group of patients with diffuse compared to segmental lesions (28 vs. 16 mg/dL, p = 0.023) and in the group with calcinosis compared to the group without it (35 vs. 19 mg/dL, p = 0.046). Lp(a) ≥ 30 mg/dL was associated with the presence of diffuse lesions (OR = 2.18 (95% CI 1.34–3.54), p = 0.002), calcinosis (2.15 (1.15–4.02), p = 0.02), and its combination (4.30 (1.81–10.19), p = 0.0009), irrespective of other risk factors. The risk of MACE within one year after CABG was higher for patients with combined diffuse and calcified lesions vs. patients with a segmental lesion without calcinosis (relative risk = 2.38 (1.13–5.01), p = 0.02). Conclusion: Diffuse atherosclerosis and coronary calcinosis are associated with elevated Lp(a) levels, independent of other risk factors. The risk of MACE in the first year after surgery is significantly higher in patients with diffuse atherosclerosis and coronary calcinosis, which should be considered when prescribing postoperative treatment for such patients. Full article

(This article belongs to the Special Issue Pathomechanisms of Disturbances Underlying Chronic Disorders)

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14 pages, 952 KiB

Open AccessArticle

Changes in Circadian Variations in Blood Pressure, Pain Pressure Threshold and the Elasticity of Tissue after a Whole-Body Photobiomodulation Treatment in Patients with Fibromyalgia: A Tripled-Blinded Randomized Clinical Trial

by Santiago Navarro-Ledesma, James Carroll, Ana González-Muñoz, Leo Pruimboom and Patricia Burton

Biomedicines 2022, 10(11), 2678; https://doi.org/10.3390/biomedicines10112678 - 23 Oct 2022

Cited by 11 | Viewed by 2748

Abstract

This study analysed circadian variation changes in blood pressure (BP), the pain pressure threshold (PPT) and the elasticity of tissue in patients with fibromyalgia (FM) after a whole-body photobiomodulation (PBM) treatment. This was a tripled-blinded randomized clinical trial including forty participants with FM. [...] Read more.

This study analysed circadian variation changes in blood pressure (BP), the pain pressure threshold (PPT) and the elasticity of tissue in patients with fibromyalgia (FM) after a whole-body photobiomodulation (PBM) treatment. This was a tripled-blinded randomized clinical trial including forty participants with FM. Participants using validated self-measurement BP devices attained readings that were used to calculate the circadian variation. Additionally, a standard pressure algometer of 1cm2 was used to assess 13 tender points by exerting a pressure of up to 4 kg, and strain elastography assessed the elasticity of tissue. Circadian variations in BP showed significant differences after the PBM intervention (p = 0.036). When comparing PPT between groups, statistically significant differences were found in the occiput (p = 0.039), low cervical (p = 0.035), trapezius (p = 0.037), second rib (p < 0.001) and medial epicondyle points (p = 0.006). Furthermore, there were statistically significant differences in both the trapezius and the forearm at the distal dorsal third SEL values (p ≤ 0.001) when comparing groups. Whole-body PBM produces changes in circadian blood pressure, the pain pressure threshold and the elasticity of tissue after a treatment program was carried out. However, more studies are needed to corroborate our findings as well as to better understand the underlying mechanisms. Full article

(This article belongs to the Special Issue Pathomechanisms of Disturbances Underlying Chronic Disorders)

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11 pages, 1577 KiB

Open AccessArticle

Do Androgenic Pattern, Insulin State and Growth Hormone Affect Cardiorespiratory Fitness and Strength in Young Women with PCOS?

by Veronica Baioccato, Giulia Quinto, Sara Rovai, Francesca Conte, Francesca Dassie, Daniel Neunhäeuserer, Marco Vecchiato, Stefano Palermi, Andrea Gasperetti, Valentina Bullo, Valentina Camozzi, Roberto Vettor, Andrea Ermolao and Roberto Mioni

Biomedicines 2022, 10(9), 2176; https://doi.org/10.3390/biomedicines10092176 - 02 Sep 2022

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Abstract

In this study, cardiorespiratory fitness (CRF) and strength level were assessed in women with and without polycystic ovary syndrome (PCOS), matched for age, body composition, androgenic pattern and insulinemic pattern. Patients with and without PCOS were evaluated at the Endocrinology Unit and Sport [...] Read more.

In this study, cardiorespiratory fitness (CRF) and strength level were assessed in women with and without polycystic ovary syndrome (PCOS), matched for age, body composition, androgenic pattern and insulinemic pattern. Patients with and without PCOS were evaluated at the Endocrinology Unit and Sport Medicine Division to assess endocrinological (insulinemic, androgenic pattern and growth hormone), anthropometric (with DEXA) and functional parameters (with cardiopulmonary exercise test and handgrip test), as well as physical activity level (with the Global Physical Activity Questionnaire). A total of 31 patients with PCOS and 13 controls were included. No statistically significant differences were found between groups in terms of age, body mass index, body composition, androgenic pattern, insulin state, growth hormone and physical activity level. The PCOS group demonstrated significantly better cardiorespiratory fitness (VO₂max per kg (30.9 ± 7.6 vs. 24.8 ± 4.1 mL/kg/min; p = 0.010), VO₂max per kg of fat-free mass (52.4 ± 8.9 vs. 45.3 ± 6.2 mL/kg/min; p = 0.018)), strength levels (handgrip per kg (0.36 ± 0.09 vs. 0.30 ± 0.08; p = 0.009), handgrip per kg of fat-free mass (13.03 ± 2.32 vs. 11.50 ± 1.91; p = 0.001)) and exercise capacity (METs at test (14.4 ± 2.72 vs. 12.5 ± 1.72 METs; p = 0.019)). In this study, women with PCOS showed a better cardiorespiratory fitness and strength than the control group. The only determinant that could explain the differences observed seems to be the presence of the syndrome itself. These results suggest that PCOS per se does not limit exercise capacity and does not exclude good functional capacity. Full article

(This article belongs to the Special Issue Pathomechanisms of Disturbances Underlying Chronic Disorders)

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14 pages, 1776 KiB

Open AccessArticle

Effects of Achieving Sustained Virologic Response after Direct-Acting Antiviral Agents on Long-Term Liver Fibrosis in Diabetics vs. in Non-Diabetic Patients with Chronic Hepatitis C Infection

by Marian-Sorin Popescu, Dan-Mihai Firu, Vlad Pădureanu, Cristina Maria Mărginean, Radu Mitruț, Andreea Letitia Arsene, Dragoș Nicolae Mărgăritescu, Daniela Calina, Anca Oana Docea and Paul Mitruț

Biomedicines 2022, 10(9), 2093; https://doi.org/10.3390/biomedicines10092093 - 26 Aug 2022

Cited by 2 | Viewed by 1436

Abstract

Because of the prevalence of HCV worldwide as well as its undiagnosed population due to a lack of screening, HCV can be considered a modern pandemic disease. In 2016, the World Health Organization (WHO) set goals for HCV’s elimination that included a 65 [...] Read more.

Because of the prevalence of HCV worldwide as well as its undiagnosed population due to a lack of screening, HCV can be considered a modern pandemic disease. In 2016, the World Health Organization (WHO) set goals for HCV’s elimination that included a 65 percent reduction in mortality and an 80 percent reduction in newly infected cases by 2030. This study is a follow-up evaluation of 80 patients who received interferon-free treatment with direct-acting agents (DAA) for chronic HCV infection between the second half of 2017 and the end of 2018. They were assessed using a FibroMax test prior to DAA administration. Two pills/day of Ombitasvir 12.5 mg/Paritaprevir 75 mg/Ritonavir 50 mg and two pills/day of Dasabuvir 250 mg were given to the patients for 8 weeks. After treatment, all 80 patients in this study achieved an SVR (sustained virologic response), and the FibroMax test was performed three years later. Our study found that successfully treating HCV infection can play a significant role in reducing fibrosis in T2DM patients. In comparison to those of ActiTest and SteatoTest, FibroMax scores showed a significantly greater reduction in T2DM patients than in treatment-naive patients. Full article

(This article belongs to the Special Issue Pathomechanisms of Disturbances Underlying Chronic Disorders)

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Review

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21 pages, 787 KiB

Open AccessReview

The Role of miRNA in Renal Fibrosis Leading to Chronic Kidney Disease

by Anna Gluba-Sagr, Beata Franczyk, Magdalena Rysz-Górzyńska, Janusz Ławiński and Jacek Rysz

Biomedicines 2023, 11(9), 2358; https://doi.org/10.3390/biomedicines11092358 - 23 Aug 2023

Cited by 6 | Viewed by 1443

Abstract

Chronic kidney disease (CKD) is an important health concern that is expected to be the fifth most widespread cause of death worldwide by 2040. The presence of chronic inflammation, oxidative stress, ischemia, etc., stimulates the development and progression of CKD. Tubulointerstitial fibrosis is [...] Read more.

Chronic kidney disease (CKD) is an important health concern that is expected to be the fifth most widespread cause of death worldwide by 2040. The presence of chronic inflammation, oxidative stress, ischemia, etc., stimulates the development and progression of CKD. Tubulointerstitial fibrosis is a common pathomechanism of renal dysfunction, irrespective of the primary origin of renal injury. With time, fibrosis leads to end-stage renal disease (ESRD). Many studies have demonstrated that microRNAs (miRNAs, miRs) are involved in the onset and development of fibrosis and CKD. miRNAs are vital regulators of some pathophysiological processes; therefore, their utility as therapeutic agents in various diseases has been suggested. Several miRNAs were demonstrated to participate in the development and progression of kidney disease. Since renal fibrosis is an important problem in chronic kidney disease, many scientists have focused on the determination of miRNAs associated with kidney fibrosis. In this review, we present the role of several miRNAs in renal fibrosis and the potential pathways involved. However, as well as those mentioned above, other miRs have also been suggested to play a role in this process in CKD. The reports concerning the impact of some miRNAs on fibrosis are conflicting, probably because the expression and regulation of miRNAs occur in a tissue- and even cell-dependent manner. Moreover, different assessment modes and populations have been used. There is a need for large studies and clinical trials to confirm the role of miRs in a clinical setting. miRNAs have great potential; thus, their analysis may improve diagnostic and therapeutic strategies. Full article

(This article belongs to the Special Issue Pathomechanisms of Disturbances Underlying Chronic Disorders)

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19 pages, 846 KiB

Open AccessReview

SGLT2 Inhibitors in Chronic Kidney Disease: From Mechanisms to Clinical Practice

by Roko Skrabic, Marko Kumric, Josip Vrdoljak, Doris Rusic, Ivna Skrabic, Marino Vilovic, Dinko Martinovic, Vid Duplancic, Tina Ticinovic Kurir and Josko Bozic

Biomedicines 2022, 10(10), 2458; https://doi.org/10.3390/biomedicines10102458 - 01 Oct 2022

Cited by 11 | Viewed by 8143

Abstract

In recent years, sodium-glucose co-transporter 2 inhibitors (SGLT2i) have demonstrated beneficial renoprotective effects, which culminated in the recent approval of their use for patients with chronic kidney disease (CKD), following a similar path to one they had already crossed due to their cardioprotective [...] Read more.

In recent years, sodium-glucose co-transporter 2 inhibitors (SGLT2i) have demonstrated beneficial renoprotective effects, which culminated in the recent approval of their use for patients with chronic kidney disease (CKD), following a similar path to one they had already crossed due to their cardioprotective effects, meaning that SGLT2i represent a cornerstone of heart failure therapy. In the present review, we aimed to discuss the pathophysiological mechanisms operating in CKD that are targeted with SGLT2i, either directly or indirectly. Furthermore, we presented clinical evidence of SGLT2i in CKD with respect to the presence of diabetes mellitus. Despite initial safety concerns with regard to euglycemic diabetic ketoacidosis and transient decline in glomerular filtration rate, the accumulating clinical data are reassuring. In summary, although SGLT2i provide clinicians with an exciting new treatment option for patients with CKD, further research is needed to determine which subgroups of patients with CKD will benefit the most, and which the least, from this therapeutical option. Full article

(This article belongs to the Special Issue Pathomechanisms of Disturbances Underlying Chronic Disorders)

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