Biomedicines

12 pages, 1427 KiB

Open AccessReview

The Monocrotaline Rat Model of Right Heart Disease Induced by Pulmonary Artery Hypertension

by Anna Maria Krstic, Timothy L. M. Jones, Amelia S. Power and Marie-Louise Ward

Biomedicines 2024, 12(9), 1944; https://doi.org/10.3390/biomedicines12091944 - 23 Aug 2024

Pulmonary artery hypertension (PAH) is characterised by increased pulmonary vascular resistance (PVR) resulting in elevated pressure in the pulmonary artery supplying the pulmonary circulation. Disease of the right ventricle (RV) often manifests as a result of PAH placing excessive pressure on the right [...] Read more.

Pulmonary artery hypertension (PAH) is characterised by increased pulmonary vascular resistance (PVR) resulting in elevated pressure in the pulmonary artery supplying the pulmonary circulation. Disease of the right ventricle (RV) often manifests as a result of PAH placing excessive pressure on the right side of the heart. Although a relatively rare disease in humans, the impact of sustained PAH is severe, with poor outcomes even in treated individuals. As PAH develops, the blood flow is restricted through the pulmonary arteries and the right ventricle hypertrophies due to the increased strain of pumping blood through the pulmonary circulation. With time, RV hypertrophy progresses to right heart failure, impacting the supply of blood to the left ventricle and systemic circulation. Although right heart failure can currently be treated, it cannot be cured. There is therefore a need for more research into the physiological changes that cause the heart to fail under pressure overload. This review aims to evaluate the monocrotaline (MCT) rat model of PAH as a means of studying the cellular mechanisms associated with the development of RV hypertrophy and right heart failure. Full article

(This article belongs to the Special Issue Animal Models for the Study of Cardiovascular Physiology)

16 pages, 1655 KiB

Open AccessSystematic Review

Comparative Efficacy and Safety of Weekly GLP-1/GIP Agonists vs. Weekly Insulin in Type 2 Diabetes: A Network Meta-Analysis of Randomized Controlled Trials

by Hazem Ayesh, Sajida Suhail, Suhail Ayesh and Kevin Niswender

Biomedicines 2024, 12(9), 1943; https://doi.org/10.3390/biomedicines12091943 - 23 Aug 2024

Abstract

Background: Diabetes mellitus (DM) significantly impacts global health due to its complications and the economic burden it places on healthcare systems. The rise of novel once-weekly diabetes medications with different mechanisms of action necessitates an evaluation of their relative efficacy and safety. Objectives: [...] Read more.

Background: Diabetes mellitus (DM) significantly impacts global health due to its complications and the economic burden it places on healthcare systems. The rise of novel once-weekly diabetes medications with different mechanisms of action necessitates an evaluation of their relative efficacy and safety. Objectives: This study compares the efficacy and tolerability of once-weekly insulin analogs (icodec and BIF) with once-weekly GLP-1/GIP agonists (semaglutide, exenatide, tirzepatide, dulaglutide) in managing type 2 diabetes mellitus (T2DM). Methods: We conducted a network meta-analysis (NMA) using data from randomized controlled trials (RCTs) that compared these treatments with a baseline of daily basal insulin. Primary outcomes included changes in HbA1c, body weight, and tolerability. Results: The analysis integrated data from 25 RCTs, involving 18,257 patients. Tirzepatide significantly outperformed other treatments in reducing HbA1c and promoting weight loss. Weekly insulins, compared to GLP-1/GIP agonists, showed a more tolerable profile and were beneficial for certain patient demographics emphasizing weight stability. Conclusion: Our findings suggest that while once-weekly GLP-1/GIP agonists provide superior glycemic control and weight management, weekly insulins offer viable options for patients prioritizing fewer side effects and weight stability. This comprehensive comparison aids in refining personalized treatment strategies for T2DM management. Full article

(This article belongs to the Special Issue Diabetes: Comorbidities, Therapeutics and Insights)

20 pages, 950 KiB

Open AccessReview

Renal Fibrosis: SIRT1 Still of Value

by Huailiang Wu, Zhen Qiu, Liyan Wang and Wei Li

Biomedicines 2024, 12(9), 1942; https://doi.org/10.3390/biomedicines12091942 - 23 Aug 2024

Abstract

Chronic kidney disease (CKD) is a major global health concern. Renal fibrosis, a prevalent outcome regardless of the initial cause, ultimately leads to end-stage renal disease. Glomerulosclerosis and renal interstitial fibrosis are the primary pathological features. Preventing and slowing renal fibrosis are considered [...] Read more.

Chronic kidney disease (CKD) is a major global health concern. Renal fibrosis, a prevalent outcome regardless of the initial cause, ultimately leads to end-stage renal disease. Glomerulosclerosis and renal interstitial fibrosis are the primary pathological features. Preventing and slowing renal fibrosis are considered effective strategies for delaying CKD progression. However, effective treatments are lacking. Sirtuin 1 (SIRT1), a nicotinamide adenine dinucleotide (NAD⁺)-dependent deacetylase belonging to class III histone deacetylases, is implicated in the physiological regulation and protection of the kidney and is susceptible to a diverse array of pathological influences, as demonstrated in previous studies. Interestingly, controversial conclusions have emerged as research has progressed. This review provides a comprehensive summary of the current understanding and advancements in the field; specifically, the biological roles and mechanisms of SIRT1 in regulating renal fibrosis progression. These include aspects such as lipid metabolism, epithelial-mesenchymal transition, oxidative stress, aging, inflammation, and autophagy. This manuscript explores the potential of SIRT1 as a therapeutic target for renal fibrosis and offers new perspectives on treatment approaches and prognostic assessments. Full article

(This article belongs to the Special Issue Molecular Mechanisms and Novel Therapies for Chronic Kidney Disease: Focus on Diabetic Kidney Disease)

20 pages, 55586 KiB

Open AccessReview

Uncovering the Contrasts and Connections in PASC: Viral Load and Cytokine Signatures in Acute COVID-19 versus Post-Acute Sequelae of SARS-CoV-2 (PASC)

by Brandon Compeer, Tobias R. Neijzen, Steven F. L. van Lelyveld, Byron E. E. Martina, Colin A. Russell and Marco Goeijenbier

Biomedicines 2024, 12(9), 1941; https://doi.org/10.3390/biomedicines12091941 - 23 Aug 2024

Abstract

The recent global COVID-19 pandemic has had a profound and enduring impact, resulting in substantial loss of life. The scientific community has responded unprecedentedly by investigating various aspects of the crisis, particularly focusing on the acute phase of COVID-19. The roles of the [...] Read more.

The recent global COVID-19 pandemic has had a profound and enduring impact, resulting in substantial loss of life. The scientific community has responded unprecedentedly by investigating various aspects of the crisis, particularly focusing on the acute phase of COVID-19. The roles of the viral load, cytokines, and chemokines during the acute phase and in the context of patients who experienced enduring symptoms upon infection, so called Post-Acute Sequelae of COVID-19 or PASC, have been studied extensively. Here, in this review, we offer a virologist’s perspective on PASC, highlighting the dynamics of SARS-CoV-2 viral loads, cytokines, and chemokines in different organs of patients across the full clinical spectrum of acute-phase disease. We underline that the probability of severe or critical disease progression correlates with increased viral load levels detected in the upper respiratory tract (URT), lower respiratory tract (LRT), and plasma. Acute-phase viremia is a clear, although not unambiguous, predictor of PASC development. Moreover, both the quantity and diversity of functions of cytokines and chemokines increase with acute-phase disease severity. Specific cytokines remain or become elevated in the PASC phase, although the driving factor of ongoing inflammation found in patients with PASC remains to be investigated. The key findings highlighted in this review contribute to a further understanding of PASC and their differences and overlap with acute disease. Full article

(This article belongs to the Special Issue Latest Research in Post-COVID (Long COVID): Pathological and Treatment Studies of Sequelae and Complications—2nd Edition)

► Show Figures

Figure 1

11 pages, 343 KiB

Open AccessArticle

New-Onset Chronic Musculoskeletal Pain Following COVID-19 Infection Fulfils the Fibromyalgia Clinical Syndrome Criteria: A Preliminary Study

by Omar Khoja, Matthew Mulvey, Sarah Astill, Ai Lyn Tan and Manoj Sivan

Biomedicines 2024, 12(9), 1940; https://doi.org/10.3390/biomedicines12091940 - 23 Aug 2024

Abstract

New-onset chronic musculoskeletal (MSK) pain (>3 months duration) is a common symptom of post-COVID-19 syndrome (PCS). This study aimed to characterise new-onset chronic MSK pain in patients with PCS and its overlap with Fibromyalgia Syndrome (FMS). We enrolled patients with new-onset chronic MSK [...] Read more.

New-onset chronic musculoskeletal (MSK) pain (>3 months duration) is a common symptom of post-COVID-19 syndrome (PCS). This study aimed to characterise new-onset chronic MSK pain in patients with PCS and its overlap with Fibromyalgia Syndrome (FMS). We enrolled patients with new-onset chronic MSK pain post-COVID-19 and assessed the nature of the pain and associated symptoms using the C19-YRS (Yorkshire Rehabilitation Scale). The FMS assessment was conducted as part of a standard clinical examination using the American College of Rheumatology (ACR) 2010 criteria: (1) Widespread Pain Index (WPI) ≥ 7 and symptoms severity (SS) score ≥ 5, or WPI between 3 and 6 and SS score ≥ 9, (2) symptoms consistent for at least 3 months, and (3) no alternative diagnosis. Of the eighteen patients (average age 49.6 (SD 11.8) years; BMI 31.7 (SD 8.6)), twelve were female. The average symptom duration was 27.9 (SD 6.97) months post-infection. Thirteen patients (72.2%) met the FMS criteria, with an average WPI score of 8.8 and an average SS score of 8.2, indicating a high level of pain and significant quality of life impacts. These findings support the hypothesis that FMS may develop as a long-term sequela of a viral infection, underscoring the need for further research into post-viral long-term conditions. Full article

(This article belongs to the Special Issue Advanced Research on Fibromyalgia (2nd Edition))

24 pages, 2674 KiB

Open AccessReview

Novel Factors Regulating Proliferation, Migration, and Differentiation of Fibroblasts, Keratinocytes, and Vascular Smooth Muscle Cells during Wound Healing

by Jacob Smith and Vikrant Rai

Biomedicines 2024, 12(9), 1939; https://doi.org/10.3390/biomedicines12091939 - 23 Aug 2024

Abstract

Chronic diabetic foot ulcers (DFUs) are a significant complication of diabetes mellitus, often leading to amputation, increased morbidity, and a substantial financial burden. Even with the advancements in the treatment of DFU, the risk of amputation still exists, and this occurs due to [...] Read more.

Chronic diabetic foot ulcers (DFUs) are a significant complication of diabetes mellitus, often leading to amputation, increased morbidity, and a substantial financial burden. Even with the advancements in the treatment of DFU, the risk of amputation still exists, and this occurs due to the presence of gangrene and osteomyelitis. Nonhealing in a chronic DFU is due to decreased angiogenesis, granulation tissue formation, and extracellular matrix remodeling in the presence of persistent inflammation. During wound healing, the proliferation and migration of fibroblasts, smooth muscle cells, and keratinocytes play a critical role in extracellular matrix (ECM) remodeling, angiogenesis, and epithelialization. The molecular factors regulating the migration, proliferation, and differentiation of these cells are scarcely discussed in the literature. The literature review identifies the key factors influencing the proliferation, migration, and differentiation of fibroblasts, keratinocytes, and vascular smooth muscle cells (VSMCs), which are critical in wound healing. This is followed by a discussion on the various novel factors regulating the migration, proliferation, and differentiation of these cells but not in the context of wound healing; however, they may play a role. Using a network analysis, we examined the interactions between various factors, and the findings suggest that the novel factors identified may play a significant role in promoting angiogenesis, granulation tissue formation, and extracellular matrix remodeling during wound healing or DFU healing. However, these interactions warrant further investigation to establish their role alone or synergistically. Full article

(This article belongs to the Special Issue Medications for the Treatment of Diabetes)

12 pages, 623 KiB

Open AccessArticle

Prior Appendicectomy and Gut Microbiota Re-Establishment in Adults after Bowel Preparation and Colonoscopy

by Amelia J. McGuinness, Martin O’Hely, Douglas Stupart, David Watters, Samantha L. Dawson, Christopher Hair, Michael Berk, Mohammadreza Mohebbi, Amy Loughman, Glenn Guest and Felice N. Jacka

Biomedicines 2024, 12(9), 1938; https://doi.org/10.3390/biomedicines12091938 - 23 Aug 2024

Abstract

Emerging evidence suggests that the human vermiform appendix is not a vestigial organ but rather an immunological organ of biological relevance. It is hypothesised that the appendix acts as a bacterial ‘safe house’ for commensal gut bacteria and facilitates re-inoculation of the colon [...] Read more.

Emerging evidence suggests that the human vermiform appendix is not a vestigial organ but rather an immunological organ of biological relevance. It is hypothesised that the appendix acts as a bacterial ‘safe house’ for commensal gut bacteria and facilitates re-inoculation of the colon after disruption through the release of biofilms. To date, no studies have attempted to explore this potential mechanistic function of the appendix. We conducted a pre-post intervention study in adults (n = 59) exploring re-establishment of the gut microbiota in those with and without an appendix after colonic disruption via bowel preparation and colonoscopy. Gut microbiota composition was measured one week before and one month after bowel preparation and colonoscopy using 16S rRNA sequencing. We observed between group differences in gut microbiota composition between those with (n = 45) and without (n = 13) an appendix at baseline. These differences were no longer evident one-month post-procedure, suggesting that this procedure may have ‘reset’ any potential appendix-related differences between groups. Both groups experienced reductions in gut microbiota richness and shifts in beta diversity post-procedure, with greater changes in those without an appendix, and there were five bacterial genera whose re-establishment post-procedure appeared to be moderated by appendicectomy status. This small experimental study provides preliminary evidence of a potential differential re-establishment of the gut microbiota after disruption in those with and without an appendix, warranting further investigation into the potential role of the appendix as a microbial safe house. Full article

(This article belongs to the Special Issue Advanced Research of Gut Microbiota in Health and Diseases)

► Show Figures

Figure 1

23 pages, 3087 KiB

Open AccessReview

Animal Models of Retinopathy of Prematurity: Advances and Metabolic Regulators

by Meenakshi Maurya, Chi-Hsiu Liu, Kiran Bora, Neetu Kushwah, Madeline C. Pavlovich, Zhongxiao Wang and Jing Chen

Biomedicines 2024, 12(9), 1937; https://doi.org/10.3390/biomedicines12091937 - 23 Aug 2024

Abstract

Retinopathy of prematurity (ROP) is a primary cause of visual impairment and blindness in premature newborns, characterized by vascular abnormalities in the developing retina, with microvascular alteration, neovascularization, and in the most severe cases retinal detachment. To elucidate the pathophysiology and develop therapeutics [...] Read more.

Retinopathy of prematurity (ROP) is a primary cause of visual impairment and blindness in premature newborns, characterized by vascular abnormalities in the developing retina, with microvascular alteration, neovascularization, and in the most severe cases retinal detachment. To elucidate the pathophysiology and develop therapeutics for ROP, several pre-clinical experimental models of ROP were developed in different species. Among them, the oxygen-induced retinopathy (OIR) mouse model has gained the most popularity and critically contributed to our current understanding of pathological retinal angiogenesis and the discovery of potential anti-angiogenic therapies. A deeper comprehension of molecular regulators of OIR such as hypoxia-inducible growth factors including vascular endothelial growth factors as primary perpetrators and other new metabolic modulators such as lipids and amino acids influencing pathological retinal angiogenesis is also emerging, indicating possible targets for treatment strategies. This review delves into the historical progressions that gave rise to the modern OIR models with a focus on the mouse model. It also reviews the fundamental principles of OIR, recent advances in its automated assessment, and a selected summary of metabolic investigation enabled by OIR models including amino acid transport and metabolism. Full article

(This article belongs to the Special Issue Angiogenesis)

► Show Figures

Figure 1

20 pages, 1674 KiB

Open AccessReview

Decoding Pulmonary Embolism: Pathophysiology, Diagnosis, and Treatment

by Miriam Peracaula, Laura Sebastian, Iria Francisco, Marc Bonnin Vilaplana, Diego A. Rodríguez-Chiaradía and Olga Tura-Ceide

Biomedicines 2024, 12(9), 1936; https://doi.org/10.3390/biomedicines12091936 - 23 Aug 2024

Abstract

Pulmonary Embolism (PE) is a life-threatening condition initiated by the presence of blood clots in the pulmonary arteries, leading to severe morbidity and mortality. Underlying mechanisms involve endothelial dysfunction, including impaired blood flow regulation, a pro-thrombotic state, inflammation, heightened oxidative stress, and altered [...] Read more.

Pulmonary Embolism (PE) is a life-threatening condition initiated by the presence of blood clots in the pulmonary arteries, leading to severe morbidity and mortality. Underlying mechanisms involve endothelial dysfunction, including impaired blood flow regulation, a pro-thrombotic state, inflammation, heightened oxidative stress, and altered vascular remodeling. These mechanisms contribute to vascular diseases stemming from PE, such as recurrent thromboembolism, chronic thromboembolic pulmonary hypertension, post-thrombotic syndrome, right heart failure, and cardiogenic shock. Detailing key risk factors and utilizing hemodynamic stability-based categorization, the review aims for precise risk stratification by applying established diagnostic tools and scoring systems. This article explores both conventional and emerging biomarkers as potential diagnostic tools. Additionally, by synthesizing existing knowledge, it provides a comprehensive outlook of the current enhanced PE management and preventive strategies. The conclusion underscores the need for future research to improve diagnostic accuracy and therapeutic effectiveness in PE. Full article

(This article belongs to the Special Issue Role of Endothelial Cells in Cardiovascular Disease)

► Show Figures

Figure 1

10 pages, 727 KiB

Open AccessArticle

Serum Uric Acid as an Indicator of Right Ventricular Dysfunction in LVAD Patients: A Preliminary Study

by Tomasz Urbanowicz, Małgorzata Tomaszewska, Anna Olasińska-Wiśniewska, Jędrzej Sikora, Ewa Straburzyńska-Migaj, Jakub Piecek, Maksymilian Białasik-Misiorny, Aleksandra Krasińska-Płachta, Andrzej Tykarski and Marek Jemielity

Biomedicines 2024, 12(9), 1935; https://doi.org/10.3390/biomedicines12091935 - 23 Aug 2024

Abstract

(1) Background: Left ventricular assist devices (LVADs) represent mechanical support in end-stage congestive heart failure and are characterized by satisfactory long-term results. Uric acid (UA) represents one of the early heart failure markers whose usefulness was postulated in clinical practice. (2) Methods: Twenty-nine [...] Read more.

(1) Background: Left ventricular assist devices (LVADs) represent mechanical support in end-stage congestive heart failure and are characterized by satisfactory long-term results. Uric acid (UA) represents one of the early heart failure markers whose usefulness was postulated in clinical practice. (2) Methods: Twenty-nine male patients with a median age of 58 (51–62) years were referred for LVAD implantation due to end-stage congestive heart failure in the mean (SD) New York Heart Association (NYHA) status class 3.3 (0.6). Preoperative and postoperative right ventricular (RV) characteristics were compared with serum uric acid concentration within 12 (8–15) months following the implantation. (3) Results: Significant correlations between postoperative uric acid concentration and right ventricular dimension (r = 0.604, p = 0.005), tricuspid annulus plane systolic excursion (TAPSE) (r = −0.496, p = 0.022), left ventricular ejection fraction (r = −0.463, p = 0.046), and N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) (r = 0.505, p = 0.041) were noted. (4) Conclusions: The analysis shows the association between the postoperative RV diameter and TAPSE results in LVAD patients and uric acid concentration. Serum uric acid can be regarded as a possible right ventricular dysfunction marker in LVAD patients. Full article

(This article belongs to the Section Molecular and Translational Medicine)

► Show Figures

Figure 1

32 pages, 4179 KiB

Open AccessArticle

Analysis of Sigma-1 Receptor Antagonist BD1047 Effect on Upregulating Proteins in HIV-1-Infected Macrophages Exposed to Cocaine Using Quantitative Proteomics

by Omar Vélez-López, Kelvin Carrasquillo-Carrión, Yadira M. Cantres-Rosario, Eraysy Machín-Martínez, Manuel E. Álvarez-Ríos, Abiel Roche-Lima, Eduardo L. Tosado-Rodríguez and Loyda M. Meléndez

Biomedicines 2024, 12(9), 1934; https://doi.org/10.3390/biomedicines12091934 - 23 Aug 2024

Abstract

HIV-1 infects monocyte-derived macrophages (MDM) that migrate into the brain and secrete virus and neurotoxic molecules, including cathepsin B (CATB), causing cognitive dysfunction. Cocaine potentiates CATB secretion and neurotoxicity in HIV-infected MDM. Pretreatment with BD1047, a sigma-1 receptor antagonist, before cocaine exposure reduces [...] Read more.

HIV-1 infects monocyte-derived macrophages (MDM) that migrate into the brain and secrete virus and neurotoxic molecules, including cathepsin B (CATB), causing cognitive dysfunction. Cocaine potentiates CATB secretion and neurotoxicity in HIV-infected MDM. Pretreatment with BD1047, a sigma-1 receptor antagonist, before cocaine exposure reduces HIV-1, CATB secretion, and neuronal apoptosis. We aimed to elucidate the intracellular pathways modulated by BD1047 in HIV-infected MDM exposed to cocaine. We hypothesized that the Sig1R antagonist BD1047, prior to cocaine, significantly deregulates proteins and pathways involved in HIV-1 replication and CATB secretion that lead to neurotoxicity. MDM culture lysates from HIV-1-infected women treated with BD1047 before cocaine were compared with untreated controls using TMT quantitative proteomics, bioinformatics, Lima statistics, and pathway analyses. Results demonstrate that pretreatment with BD1047 before cocaine dysregulated eighty (80) proteins when compared with the infected cocaine group. We found fifteen (15) proteins related to HIV-1 infection, CATB, and mitochondrial function. Upregulated proteins were related to oxidative phosphorylation (SLC25A-31), mitochondria (ATP5PD), ion transport (VDAC2–3), endoplasmic reticulum transport (PHB, TMED10, CANX), and cytoskeleton remodeling (TUB1A-C, ANXA1). BD1047 treatment protects HIV-1-infected MDM exposed to cocaine by upregulating proteins that reduce mitochondrial damage, ER transport, and exocytosis associated with CATB-induced neurotoxicity. Full article

(This article belongs to the Special Issue Sigma-1 Receptor in Health and Disease)

► Show Figures

Figure 1

13 pages, 4002 KiB

Open AccessArticle

Calcium-Enhanced Medium-Based Delivery of Splice Modulating Antisense Oligonucleotides in 2D and 3D hiPSC-Derived Neuronal Models

by Ronald A. M. Buijsen, Linda M. van der Graaf, Elsa C. Kuijper, Barry A. Pepers, Elena Daoutsali, Lotte Weel, Vered Raz, David A. Parfitt and Willeke M. C. van Roon-Mom

Biomedicines 2024, 12(9), 1933; https://doi.org/10.3390/biomedicines12091933 - 23 Aug 2024

Abstract

Antisense technology demonstrates significant potential for addressing inherited brain diseases, with over a dozen products already available and numerous others in the development pipeline. The versatility of differentiating induced pluripotent stem cells (iPSCs) into nearly all neural cell types proves invaluable for comprehending [...] Read more.

Antisense technology demonstrates significant potential for addressing inherited brain diseases, with over a dozen products already available and numerous others in the development pipeline. The versatility of differentiating induced pluripotent stem cells (iPSCs) into nearly all neural cell types proves invaluable for comprehending the mechanisms behind neurological diseases, replicating cellular phenotypes, and advancing the testing and development of new therapies, including antisense oligonucleotide therapeutics. While delivering antisense oligonucleotides (ASOs) to human iPSC-based neuronal models has posed challenges, this study explores various delivery methods, including lipid-based transfection, gymnotic uptake, Ca⁽²⁺⁾-enhanced medium (CEM)-based delivery, and electroporation, in 2D and 3D hiPSC-derived neuronal models. This study reveals that CEM-based delivery exhibits efficiency and low toxicity in both 2D neuronal cultures and 3D brain organoids. Furthermore, the findings indicate that CEM is slightly more effective in neurons than in astrocytes, suggesting promising avenues for further exploration and optimization of preclinical ASO strategies in the treatment of neurological disorders. Full article

(This article belongs to the Special Issue Applications of 3D Cell Culture in Biomedicines)

► Show Figures

Figure 1

18 pages, 1786 KiB

Open AccessReview

Association between the Exposure to Phthalates and the Risk of Endometriosis: An Updated Review

by Bárbara Ribeiro, Melissa Mariana, Margarida Lorigo, Denise Oliani, Ana Cristina Ramalhinho and Elisa Cairrao

Biomedicines 2024, 12(8), 1932; https://doi.org/10.3390/biomedicines12081932 - 22 Aug 2024

Abstract

Endometriosis is a chronic gynecological disease, primarily associated with pelvic pain and infertility, that affects approximately 10% of the women of reproductive age. Estrogen plays a central role in endometriosis, and there is growing evidence that endocrine disruptors, such as phthalates, may contribute [...] Read more.

Endometriosis is a chronic gynecological disease, primarily associated with pelvic pain and infertility, that affects approximately 10% of the women of reproductive age. Estrogen plays a central role in endometriosis, and there is growing evidence that endocrine disruptors, such as phthalates, may contribute to its development. This review aimed to determine whether there is a causal relationship between phthalate exposure and the development of endometriosis, as well as the possible effects of phthalates on fertility, by analyzing epidemiological data. After a literature search with a combination of specific terms on this topic, we found that although there are limitations to the current studies, there is a clear association between phthalate exposure and endometriosis. Phthalates can interfere with the cellular processes of the endometrium; specifically, they can bind to PPAR and ER-α and activate TGF-β, promoting different signaling cascades that regulate the expression of specific target genes. This may lead to inflammation, invasion, cytokine alteration, increased oxidative stress, and impaired cell viability and proliferation, culminating in endometriosis. Nevertheless, future research is important to curb the progression and development of endometriosis, and strategies for prevention, diagnosis, and treatment are a priority. In this regard, public policies and recommendations to reduce exposure to phthalates and other endocrine disruptors should be promptly implemented. Full article

(This article belongs to the Special Issue Pollutants and Human Health: Focus on Molecular-Level Research)

► Show Figures

Figure 1

13 pages, 1326 KiB

Open AccessReview

Could the Early Detection of Atrial Fibrillation Reduce the Risk of Developing Dementia?

by Fabrice Demoniere, Rim Abdelli and Léna Rivard

Biomedicines 2024, 12(8), 1931; https://doi.org/10.3390/biomedicines12081931 - 22 Aug 2024

Abstract

Atrial fibrillation (AF) and dementia are major global public health issues and share common risk factors, especially after the age of 65 and regardless of the presence of stroke. Despite accounting for potential confounders, AF appears to be an independent risk factor for [...] Read more.

Atrial fibrillation (AF) and dementia are major global public health issues and share common risk factors, especially after the age of 65 and regardless of the presence of stroke. Despite accounting for potential confounders, AF appears to be an independent risk factor for cognitive decline and dementia. The mechanisms are likely to be multifactorial and may include AF-related ischemic stroke, cerebral hypoperfusion, microbleeds, systemic inflammation, genetic factors, and small vessel disease, leading to brain atrophy and white matter damage. The early aggressive management of AF and comorbidities may reduce the risk of dementia. Indeed, the early detection of AF-related cognitive impairment should allow for the early implementation of measures to prevent the development of dementia, mainly through integrative approaches involving the correction of risk factors and maintenance of rhythm control. Well-designed prospective studies are needed to determine whether early detection and AF treatment can prevent dementia and identify whether optimal integrative measures are effective in preventing cognitive impairment and dementia. Full article

(This article belongs to the Special Issue Advanced Research in Atrial Fibrillation)

► Show Figures

Figure 1

14 pages, 893 KiB

Open AccessReview

Selective COX-2 Inhibitors as Neuroprotective Agents in Traumatic Brain Injury

by Matthew I. Hiskens, Anthony G. Schneiders and Andrew S. Fenning

Biomedicines 2024, 12(8), 1930; https://doi.org/10.3390/biomedicines12081930 - 22 Aug 2024

Abstract

Traumatic brain injury (TBI) is a significant contributor to mortality and morbidity in people, both young and old. There are currently no approved therapeutic interventions for TBI. Following TBI, cyclooxygenase (COX) enzymes generate prostaglandins and reactive oxygen species that perpetuate inflammation, with COX-1 [...] Read more.

Traumatic brain injury (TBI) is a significant contributor to mortality and morbidity in people, both young and old. There are currently no approved therapeutic interventions for TBI. Following TBI, cyclooxygenase (COX) enzymes generate prostaglandins and reactive oxygen species that perpetuate inflammation, with COX-1 and COX-2 isoforms providing differing responses. Selective COX-2 inhibitors have shown potential as neuroprotective agents. Results from animal models of TBI suggest potential treatment through the alleviation of secondary injury mechanisms involving neuroinflammation and neuronal cell death. Additionally, early clinical trials have shown that the use of celecoxib improves patient mortality and outcomes. This review aims to summarize the therapeutic effects of COX-2 inhibitors observed in TBI animal models, highlighting pertinent studies elucidating molecular pathways and expounding upon their mechanistic actions. We then investigated the current state of evidence for the utilization of COX-2 inhibitors for TBI patients. Full article

(This article belongs to the Special Issue Neurotrauma: Mechanisms, Pathways, and Emerging Therapeutic Interventions)

► Show Figures

Figure 1

14 pages, 1564 KiB

Open AccessArticle

Effect of Pravastatin on Placental Expression of Epidermal Growth Factor-like Domain 7 in Early-Onset Pre-Eclampsia: A New Potential Mechanism of Action

by Silvia Salvi, Stefano Fruci, Valentina Lacconi, Federica Totaro Aprile, Roberta Rullo, Heidi Stuhlmann, Antonio Lanzone, Luisa Campagnolo and Micol Massimiani

Biomedicines 2024, 12(8), 1929; https://doi.org/10.3390/biomedicines12081929 - 22 Aug 2024

Abstract

The primary intervention for pre-eclampsia (PE) remains iatrogenic delivery, which can be very preterm and not optimal for the fetus. Although many efforts have been made to prevent and manage PE, there is still a dearth of drugs to treat its pathophysiological progression. [...] Read more.

The primary intervention for pre-eclampsia (PE) remains iatrogenic delivery, which can be very preterm and not optimal for the fetus. Although many efforts have been made to prevent and manage PE, there is still a dearth of drugs to treat its pathophysiological progression. Pravastatin (PRA), a hydrophilic statin, has gained interest for the prevention and treatment of PE. The aim of the present study was to evaluate the ability of PRA to modulate factors involved in placentation, such as Epidermal Growth Factor-Like Domain 7 (EGFL7), in human chorionic villous culture from healthy controls and women with PE. A total of 18 women were enrolled: 10 controls and 8 cases. Chorionic villous explants were maintained in culture for 24 h with or without 10 μM Pravastatin, and the expression of EGFL7 and NOTCH1 pathway members was evaluated by qRT-PCR and Western blot analysis. The rationale of the present study was to establish an ex vivo model to identify potential different responses to PRA treatment of chorionic villous explants in order to clarify the molecular mechanism of PRA in the prevention and treatment of PE and to predict whether there are specific clinical conditions that modulate the response to the drug treatment. Within PE patients, two different groups were identified: the high responders, whose villous cultures exhibit significantly increased expressions of the EGFL7 and Notch pathways after PRA incubation; and the low responders, who are high-risk PE patients in which prophylaxis failed to prevent PE and PRA was not able to modulate EGFL7 expression. In conclusion, we identified EGFL7 as a new factor regulated by PRA, placing interest in early discrimination between low- and high- risk women, in which the well-known pharmacological prophylaxis seems to be ineffective, and to explore new potential prevention strategies. Full article

(This article belongs to the Special Issue Role of Factors in Embryo Implantation and Placental Development)

► Show Figures

Figure 1

20 pages, 1582 KiB

Open AccessReview

Complex Interactions between the Human Major Histocompatibility Complex (MHC) and Microbiota: Their Roles in Disease Pathogenesis and Immune System Regulation

by Antonio Arnaiz-Villena, Ignacio Juarez, Christian Vaquero-Yuste, Tomás Lledo, José Manuel Martin-Villa and Fabio Suarez-Trujillo

Biomedicines 2024, 12(8), 1928; https://doi.org/10.3390/biomedicines12081928 - 22 Aug 2024

Abstract

The relationship between microbiota and the immune system is complex and characterized by the ways in which microbiota directs immune function interactions, both innate and acquired and also keeps activating the immune system throughout an individual’s life. In this respect, the human Major [...] Read more.

The relationship between microbiota and the immune system is complex and characterized by the ways in which microbiota directs immune function interactions, both innate and acquired and also keeps activating the immune system throughout an individual’s life. In this respect, the human Major Histocompatibility Complex (MHC, referred to as HLA in humans) plays a crucial role and is also established in self-defense against microbes by presenting microbial-derived peptides to the immune cells. However, this assumption has some unclear aspects that should be investigated. For example, how is the microbiota shaped by microbe species diversity, quantity and functions of the immune system, as well as the role and molecular mechanisms of the HLA complex during this process. There are autoimmune diseases related to both HLA and specific microbiota changes or alterations, many of which are mentioned in the present review. In addition, the HLA peptide presenting function should be put in a framework together with its linkage to diseases and also with HLA compatibility necessary for transplants to be successful. These are still quite an enigmatically statistical and phenomenological approach, but no firm pathogenic mechanisms have been described; thus, HLA’s real functioning is still to be fully unveiled. After many years of HLA single-genes studies, firm pathogenesis mechanisms underlying disease linkage have been discovered. Finally, microbiota has been defined as conformed by bacteria, protozoa, archaea, fungi, and viruses; notwithstanding, endogenous viral sequences integrated into the human genome and other viral particles (obelisks) recently found in the digestive mucosa should be taken into account because they may influence both the microbiome and the immune system and their interactions. In this context, we propose to integrate these microbial-genetic particle components into the microbiome concept and designate it as “microgenobiota”. Full article

(This article belongs to the Special Issue The Interplay between Immunity and Microbiota in Human Health and Diseases (2nd Edition))

► Show Figures

Figure 1

21 pages, 6530 KiB

Open AccessArticle

Combination of Anti-CD40 and Anti-CD40L Antibodies as Co-Stimulation Blockade in Preclinical Cardiac Xenotransplantation

by Martin Bender, Jan-Michael Abicht, Bruno Reichart, Elisabeth Neumann, Julia Radan, Maren Mokelke, Ines Buttgereit, Maria Leuschen, Felicia Wall, Sebastian Michel, Reinhard Ellgass, Stig Steen, Audrius Paskevicius, Andreas Lange, Barbara Kessler, Elisabeth Kemter, Nikolai Klymiuk, Joachim Denner, Antonia W. Godehardt, Ralf R. Tönjes, Jonathan M. Burgmann, Constança Figueiredo, Anastasia Milusev, Valentina Zollet, Neda Salimi-Afjani, Alain Despont, Robert Rieben, Stephan Ledderose, Christoph Walz, Christian Hagl, David Ayares, Eckhard Wolf, Michael Schmoeckel, Paolo Brenner, Uli Binder, Michaela Gebauer, Arne Skerra and Matthias Längin Show full author list Hide full author list

Biomedicines 2024, 12(8), 1927; https://doi.org/10.3390/biomedicines12081927 - 22 Aug 2024

Abstract

The blockade of the CD40/CD40L immune checkpoint is considered essential for cardiac xenotransplantation. However, it is still unclear which single antibody directed against CD40 or CD40L (CD154), or which combination of antibodies, is better at preventing organ rejection. For example, the high doses [...] Read more.

The blockade of the CD40/CD40L immune checkpoint is considered essential for cardiac xenotransplantation. However, it is still unclear which single antibody directed against CD40 or CD40L (CD154), or which combination of antibodies, is better at preventing organ rejection. For example, the high doses of antibody administered in previous experiments might not be feasible for the treatment of humans, while thrombotic side effects were described for first-generation anti-CD40L antibodies. To address these issues, we conducted six orthotopic pig-to-baboon cardiac xenotransplantation experiments, combining a chimeric anti-CD40 antibody with an investigational long-acting PASylated anti-CD40L Fab fragment. The combination therapy effectively resulted in animal survival with a rate comparable to a previous study that utilized anti-CD40 monotherapy. Importantly, no incidence of thromboembolic events associated with the administration of the anti-CD40L PAS-Fab was observed. Two experiments failed early because of technical reasons, two were terminated deliberately after 90 days with the baboons in excellent condition and two were extended to 120 and 170 days, respectively. Unexpectedly, and despite the absence of any clinical signs, histopathology revealed fungal infections in all four recipients. This study provides, for the first time, insights into a combination therapy with anti-CD40/anti-CD40L antibodies to block this immune checkpoint. Full article

(This article belongs to the Special Issue Xenotransplantation: Targeting Acute Vascular Rejection and Endothelial Activation)

► Show Figures

Figure 1

17 pages, 853 KiB

Open AccessReview

Heart Transplant Rejection: From the Endomyocardial Biopsy to Gene Expression Profiling

by Anca Otilia Farcas, Mihai Ciprian Stoica, Ioana Maria Maier, Adrian Cornel Maier and Anca Ileana Sin

Biomedicines 2024, 12(8), 1926; https://doi.org/10.3390/biomedicines12081926 - 22 Aug 2024

Abstract

Heart transplant prolongs life for patients with end-stage heart failure but rejection remains a complication that reduces long-term survival. The aim is to provide a comprehensive overview of the current status in HT rejection. EMB is an invasive diagnostic tool, consisting in the [...] Read more.

Heart transplant prolongs life for patients with end-stage heart failure but rejection remains a complication that reduces long-term survival. The aim is to provide a comprehensive overview of the current status in HT rejection. EMB is an invasive diagnostic tool, consisting in the sampling of a fragment of myocardial tissue from the right ventricular septum using fluoroscopic guidance. This tissue can later be subjected to histopathological, immunohistochemical or molecular analysis, providing valuable information for cardiac allograft rejection, but this procedure is not without complications. To increase the accuracy of the rejection diagnosis, EMB requires a systematic evaluation of endocardium, myocardium, interstitium and intramural vessels. There are three types of rejection: hyperacute, acute or chronic, diagnosed by the histopathological evaluation of EMB as well as by new diagnostic methods such as DSA, ddcfDNA and gene expression profiling, the last having a high negative predictive value. More than 50 years after the introduction of EMB in medical practice, it still remains the “gold standard” in monitoring rejection in HT recipients but other new, less invasive diagnostic methods reduce the number of EMBs required. Full article

(This article belongs to the Special Issue An Update on Transplantation Immunology)

► Show Figures

Figure 1

Journal Description

Biomedicines

Latest Articles

Journal Menu

Journal Browser

Highly Accessed Articles

Latest Books

E-Mail Alert

News

Topics

Conferences

Special Issues

Topical Collections

Further Information

Guidelines

MDPI Initiatives

Follow MDPI