Search Results (768)

Atherosclerosis involves an inflammatory response due to plaque formation within the arteries, which can lead to ischemic stroke and heart disease. It is one of the leading causes of death worldwide, with various contributing factors such as hyperlipidemia, hypertension, obesity, diabetes, and smoking. Wall shear stress (WSS) is also known as a contributing factor of the formation of atherosclerotic plaques. Since the causes of atherosclerosis cannot be attributed to a single factor, clearly understanding the mechanisms and causes of its occurrence is crucial for preventing the disease and developing effective treatment strategies. To better understand atherosclerosis and define the correlation between various contributing factors, computational fluid dynamics (CFD) analysis is primarily used. CFD simulates WSS, the frictional force caused by blood flow on the vessel wall with various hemodynamic changes. Using apolipoprotein E knockout (ApoE-KO) mice subjected to partial ligation and a high-fat diet at 1-week, 2-week, and 4-week intervals as an atherosclerosis model, CFD analysis was conducted along with the reconstruction of carotid artery blood flow via magnetic resonance imaging (MRI) and compared to the inflammatory factors and pathological staining. In this experiment, a comparative analysis of the effects of high WSS and low WSS was conducted by comparing the standard deviation of time-averaged wall shear stress (TAWSS) at each point within the vessel wall. As a novel approach, the standard deviation of TAWSS within the vessel was analyzed with the staining results and pathological features. Since the onset of atherosclerosis cannot be explained by a single factor, the aim was to find the correlation between the thickness of atherosclerotic plaques and inflammatory factors through standard deviation analysis. As a result, the gap between low WSS and high WSS widened as the interval between weeks in the atherosclerosis mouse model increased. This finding not only linked the occurrence of atherosclerosis to WSS differences but also provided a connection to the causes of vulnerable plaques. Full article

SARS-CoV-2 infection of immunocompromised individuals often leads to prolonged detection of viral RNA and infectious virus in nasal specimens, presumably due to the lack of induction of an appropriate adaptive immune response. Mutations identified in virus sequences obtained from persistently infected patients bear signatures of immune evasion and have some overlap with sequences present in variants of concern. We characterized virus isolates obtained greater than 100 days after the initial COVID-19 diagnosis from two COVID-19 patients undergoing immunosuppressive cancer therapy, wand compared them to an isolate from the start of the infection. Isolates from an individual who never mounted an antibody response specific to SARS-CoV-2 despite the administration of convalescent plasma showed slight reductions in plaque size and some showed temperature-dependent replication attenuation on human nasal epithelial cell culture compared to the virus that initiated infection. An isolate from another patient—who did mount a SARS-CoV-2 IgM response—showed temperature-dependent changes in plaque size as well as increased syncytia formation and escape from serum-neutralizing antibodies. Our results indicate that not all virus isolates from immunocompromised COVID-19 patients display clear signs of phenotypic change, but increased attention should be paid to monitoring virus evolution in this patient population. Full article

The amyloid cascade hypothesis postulates that extracellular deposits of amyloid β (Aβ) are the primary and initial cause leading to the full development of Alzheimer’s disease (AD) with intracellular neurofibrillary tangles; however, the details of this mechanism have not been fully described until now. Our preliminary data, coming from our day-to-day neuropathology practice, show that the primary location of the hyperphosphorylated tau protein is in the vicinity of the cell membrane of dystrophic neurites. This observation inspired us to formulate a hypothesis that presumes an interaction between low-density lipoprotein receptor-related protein 1 (LRP1) and fibrillar aggregates of, particularly, Aβ₄₂ anchored at the periphery of neuritic plaques, making internalization of the LRP1-Aβ₄₂ complex infeasible and, thus, causing membrane dysfunction, leading to the tauopathy characterized by intracellular accumulation and hyperphosphorylation of the tau protein. Understanding AD as a membrane dysfunction tauopathy may draw attention to new treatment approaches not only targeting Aβ₄₂ production but also, perhaps paradoxically, preventing the formation of LRP1-Aβ₄₂. Full article

Oxidative stress constitutes a main molecular mechanism underlying cardiovascular diseases (CVDs). This pathological mechanism can be triggered by NADPH oxidases (NOXs), which produce reactive oxygen species (ROS). In fact, the different NOXs have been associated with myocardial infarction, atherothrombosis, and stroke. More specifically, we will focus on the implications of NOXs in atherothrombotic stroke. Each NOX member participates in a different way in the several stages of this disease: endothelial dysfunction, immune cell infiltration, foam cell genesis, vascular smooth muscle cells (VSMC) proliferation, and atherosclerotic plaque formation. Additionally, some NOXs are involved in plaque instability, thrombosis, ischemic stroke, and ischemia-reperfusion injury (IRI). Interestingly, the effects of NOXs in this pathology depend on the specific homolog, the cell type in which they are activated, and the stage of the disease. In this review we summarize the most up-to-date information about the implications of vascular NOXs in each of these processes. Finally, we highlight some limitations and future perspectives on the study of NOXs in CVDs. Full article

This study investigated subclinical atherosclerosis progression in low-risk, middle-aged adults (N = 141; a mean age of 49.6 ± 4.7 years) using a 5-year ultrasound follow-up. We compared the involvement of the carotid and femoral arteries. Methods: Clinical data, risk factors, carotid/femoral intima-media thickness (IMT), and plaque presence were analyzed. Results: Cardiovascular risk factors and scores increased significantly at follow-up. Both carotid and femoral mean IMT increased (p < 0.001). While plaque prevalence rose and was similar in both arteries (carotid: 4.8% to 17.9%, femoral: 3.6% to 17.7%, p < 0.001 for both), the progression of plaque burden was greater in femorals. Notably, the carotid mean IMT demonstrated a faster yearly progression rate compared to the mean femoral IMT. The prevalence of pathological nomogram-based mean IMT right or left was higher in the carotids (52.9% to 78.8%, p < 0.001) compared to femorals (23.2% to 44.7%, p < 0.001), with a significant increase at the end of follow-up in both territories. Conclusions: This study demonstrates significant subclinical atherosclerosis progression in low-risk, middle-aged adults over 5 years. Carotid arteries showed a faster progression rate of mean IMT and a higher prevalence of pathological nomogram-based mean IMT compared to the femoral arteries. However, plaque burden was similar in both territories, with greater progression in femorals. Identifying carotid and femoral atherosclerosis burden may be a valuable tool for risk stratification in this population. Full article

Toxoplasma gondii, a pathogenic apicomplexan parasite, infects approximately one third of the world’s population and poses a serious threat to global public health. Microneme proteins (MICs) secreted by the microneme, an apical secretory organelle of T. gondii, play important roles in the invasion, motility, and intracellular survival of T. gondii. In this study, we selected 11 genes of interest (GOIs) of T. gondii, tentative MICs predicted to be localized in micronemes, and we used the CRISPR-Cas9 system to construct epitope tagging strains and gene knockout strains to explore the localization and function of these 11 tentative MICs. Immunofluorescence assay showed that nine tentative MICs (TGME49_243930, TGME49_200270, TGME49_273320, TGME49_287040, TGME49_261710, TGME49_205680, TGME49_304490, TGME49_245485, and TGME49_224620) were localized or partially localized in the microneme, consistent with the prediction. However, TGME49_272380 and TGME49_243790 showed different localizations from the prediction, being localized in the endoplasmic reticulum and the dense granule, respectively. Further functional characterization of the 11 RHΔGOI strains revealed that deletion of these 11 GOIs had no significant effect on plaque formation, intracellular replication, egress, invasion ability, and virulence of T. gondii. Although these 11 GOIs are not essential genes for the growth and virulence of tachyzoites of type I RH strain, they may have potential roles in other developmental stages or other genotypes of T. gondii. Thus, further research should be performed to explore the possible role of the nine mics and the other two GOIs in other life cycle stages and other genotypes of T. gondii. Full article

Atherosclerosis is a chronic inflammatory disease that causes degenerative and productive changes in the arteries. The resulting atherosclerotic plaques restrict the vessel lumen, causing blood flow disturbances. Plaques are formed mainly in large- and medium-sized arteries, usually at bends and forks where there is turbulence in blood flow. Depending on their location, they can lead to various disease states such as myocardial infarction, stroke, renal failure, peripheral vascular diseases, or sudden cardiac death. In this work, we reviewed the literature on the early detection of atherosclerosis markers in the application of photodynamic therapy to atherosclerosis-related diseases. Herein, we described the roles of C-reactive protein, insulin, osteopontin, osteoprotegerin, copeptin, the TGF-β cytokine family, and the amino acid homocysteine. Also, we discuss the role of microelements such as iron, copper, zinc, and Vitamin D in promoting the formation of atherosclerotic plaque. Dysregulation of the administered compounds is associated with an increased risk of atherosclerosis. Additionally, taking into account the pathophysiology of atherosclerotic plaque formation, we believe that maintaining homeostasis in the range of biomarkers mentioned in this article is crucial for slowing down the process of atherosclerotic plaque development and the stability of plaque that is already formed. Full article

Atherosclerosis is a chronic inflammatory condition marked by endothelial dysfunction, lipid accumulation, inflammatory cell infiltration, and extracellular matrix (ECM) remodeling within arterial walls, leading to plaque formation and potential cardiovascular events. Key players in ECM remodeling and inflammation are matrix metalloproteinases (MMPs) and CD147/EMMPRIN, a cell surface glycoprotein expressed on endothelial cells, vascular smooth muscle cells (VSMCs), and immune cells, that regulates MMP activity. Hydrogen sulfide (H₂S), a gaseous signaling molecule, has emerged as a significant modulator of these processes including oxidative stress mitigation, inflammation reduction, and vascular remodeling. This systematic review investigates the mechanistic pathways through which H₂S influences MMPs and CD147/EMMPRIN and assesses its impact on atherosclerosis progression. A comprehensive literature search was conducted across PubMed, Scopus, and Web of Science databases, focusing on studies examining H₂S modulation of MMPs and CD147/EMMPRIN in atherosclerosis contexts. Findings indicate that H₂S modulates MMP expression and activity through transcriptional regulation and post-translational modifications, including S-sulfhydration. By mitigating oxidative stress, H₂S reduces MMP activation, contributing to plaque stability and vascular remodeling. H₂S also downregulates CD147/EMMPRIN expression via transcriptional pathways, diminishing inflammatory responses and vascular cellular proliferation within plaques. The dual regulatory role of H₂S in inhibiting MMP activity and downregulating CD147 suggests its potential as a therapeutic agent in stabilizing atherosclerotic plaques and mitigating inflammation. Further research is warranted to elucidate the precise molecular mechanisms and to explore H₂S-based therapies for clinical application in atherosclerosis. Full article

Background: Respiratory infections were found to be connected with the incidence of acute coronary syndrome (ACS). The proposed pathway of this connection includes inflammation, oxidative stress, pro-coagulation, and atherosclerotic plaque destabilization. This can cause rapture and thrombus formation, leading to ACS. Our study aimed to assess the risk factors for coronary artery thrombosis as a manifestation of ACS and for lower respiratory tract infections (LRTIs) in patients with ACS. Methods: The study included 876 patients with ACS from January 2014 to December 2018. Both the clinical data and air pollution data were analyzed. Statistical tests used for analysis included Student’s t-test, the Mann–Whitney U-test, the Chi-squared test, and the odds ratio Altman calculation. Results: LRTIs were found in 9.13% patients with ACS. The patients with LRTI had a higher risk of coronary artery thrombosis (OR: 2.4903; CI: 1.3483 to 4.5996). Moreover, they had increased values of inflammatory markers, were older, had a lower BMI, and a higher rate of atrial fibrillation. The average atmospheric aerosols with a maximum diameter of 2.5 μm (PM_2.5 concentration) from three consecutive days before hospitalization for ACS were higher in patients with LRTI. Conclusions: The occurrence of coronary artery thrombosis was higher among the patients with LRTI during ACS. PM_2.5 exposition was higher in the three consecutive days before hospitalization in patients with LRTI during ACS. Full article

Candida albicans (C. albicans) and Streptococcus mutans (S. mutans) are frequently detected in the plaque biofilms of children with early childhood caries. This study investigated the effects of sucrose and farnesol on biofilm formation by the oral pathogens S. mutans and C. albicans, including their synergistic interactions. Biofilm formation dynamics were monitored using the Cell Index (CI). The CI for S. mutans increased in the brain–heart infusion medium, peaking at 10 h; however, the addition of sucrose reduced the CI. For C. albicans yeast cells, the CI increased at sucrose concentrations > 0.5%, peaking at 2 h. Mixed cultures of S. mutans and C. albicans yeast cells showed significantly higher CI values in the presence of sucrose, suggesting a synergistic effect on biofilm formation. Farnesol consistently suppressed biofilm formation by C. albicans yeast cells, even in the presence of sucrose, and higher farnesol concentrations resulted in greater inhibition. Regarding C. albicans hyphal cells, sucrose did not enhance biofilm formation, whereas farnesol significantly reduced biofilm formation at all concentrations tested. These findings elucidate the complex roles of sucrose and farnesol in biofilm formation by S. mutans and C. albicans and emphasize the potential of farnesol as an effective oral biofilm inhibitor. Full article

Cathelicidins (human LL-37 and rat CRAMP) are multifunctional peptides involved in various cardiovascular conditions. This review integrates the recent findings about the functional involvement of LL-37/CRAMP across atherosclerosis, acute coronary syndrome, myocardial infarction, heart failure, diabetic cardiomyopathy, and platelet aggregation/thrombosis. In atherosclerosis, LL-37 interacts with scavenger receptors to modulate lipid metabolism and binds with mitochondrial DNA and lipoproteins. In acute coronary syndrome, LL-37 influences T cell responses and mitigates calcification within atherosclerotic plaques. During myocardial infarction and ischaemia/reperfusion injury, LL-37/CRAMP exhibits dual roles: protecting against myocardial damage through the AKT and ERK1/2 signalling pathways, while exacerbating inflammation via TLR4 and NLRP3 inflammasome activation. In heart failure, LL-37/CRAMP attenuates hypertrophy and fibrosis via NF-κB inhibition and the activation of the IGFR1/PI3K/AKT and TLR9/AMPK pathways. Moreover, in diabetic cardiomyopathy, these peptides alleviate oxidative stress and fibrosis by inhibiting TGFβ/Smad and AMPK/mTOR signalling and provide anti-inflammatory effects by reducing NF-κB nuclear translocation and NLRP3 inflammasome formation. LL-37/CRAMP also modulates platelet aggregation and thrombosis through the FPR2 and GPVI receptors, impacting apoptosis, autophagy, and other critical cellular processes. This comprehensive overview underscores LL-37/CRAMP as a promising therapeutic target in cardiovascular diseases, necessitating further elucidation of its intricate signalling networks and biological effects for clinical translation. Full article

Atherosclerosis is a condition that is associated with lipid accumulation in the arterial intima. Consequently, the enlarging lesion, which is also known as an atherosclerotic plaque, may close the blood vessel lumen, thus leading to organ ischaemia. Furthermore, the plaque may rupture and initiate the formation of a thrombus, which can cause acute ischaemia. Atherosclerosis is a background pathological condition that can eventually lead to major cardiovascular diseases such as acute coronary syndrome or ischaemic stroke. The disorder is associated with an altered profile of alarmins, stress response molecules that are secreted due to cell injury or death and that induce inflammatory responses. High-mobility group box 1 (HMGB1), S100 proteins, interleukin-33, and heat shock proteins (HSPs) also affect the behaviour of endothelial cells and vascular smooth muscle cells (VSMCs). Thus, alarmins control the inflammatory responses of endothelial cells and proliferation of VSMCs, two important processes implicated in the pathogenesis of atherosclerosis. In this review, we will discuss the role of alarmins in the pathophysiology of atherosclerosis and myocardial infarction. Full article

This article investigates the link between Helicobacter pylori (H. pylori) infection and cardiovascular and neurological disorders. Recent research suggests that H. pylori may play a role in cardiovascular diseases like atherosclerosis, myocardial infarction, and stroke, as well as neurological diseases including Alzheimer’s disease, multiple sclerosis, and Parkinson’s disease. Cardiovascular Diseases: H. pylori induces endothelial dysfunction and chronic inflammation, promoting atherosclerotic plaque formation and other cardiac complications. High infection prevalence in cardiovascular patients implies that systemic inflammation from H. pylori accelerates disease progression. Eradication therapies combined with anti-inflammatory and lipid-lowering treatments may reduce cardiovascular risk. Neurological Diseases: H. pylori may contribute to Alzheimer’s, multiple sclerosis, and Parkinson’s through systemic inflammation, neuroinflammation, and autoimmune responses. Increased infection prevalence in these patients suggests bacterial involvement in disease pathogenesis. The eradication of H. pylori could reduce neuroinflammation and improve outcomes. Discussions and Future Research: Managing H. pylori infection in clinical practice could impact public health and treatment approaches. Further research is needed to clarify these relationships. Longitudinal and mechanistic studies are essential to fully understand H. pylori’s role in these conditions. Conclusions: H. pylori infection is a potential risk factor for various cardiovascular and neurological conditions. Additional research is critical for developing effective prevention and treatment strategies. Targeted therapies, including H. pylori eradication combined with anti-inflammatory treatments, could improve clinical outcomes. These findings highlight the need for an integrated clinical approach to include H. pylori evaluation and treatment. Full article

Dengue, caused by the dengue virus (DENV), is a global health threat transmitted by Aedes mosquitoes, resulting in 400 million cases annually. The disease ranges from mild to severe, with potential progression to hemorrhagic dengue. Current research is focused on natural antivirals due to challenges in vector control. This study evaluates the antiviral potential of peptides derived from the microalgae Phaeodactylum tricornutum, known for its bioactive compounds. Microalgae were cultivated under controlled conditions, followed by protein extraction and hydrolysis to produce four peptide fractions. These fractions were assessed for cytotoxicity via the MTT assay and antiviral activity against DENV serotype 2 using flow cytometry and plaque formation assays. The 10–30 kDa peptide fraction, at 150 and 300 μg/mL concentrations, demonstrated no cytotoxicity and significantly reduced the percentage of infected cells and viral titers. These findings suggest that peptides derived from Phaeodactylum tricornutum exhibit promising antiviral activity against dengue virus serotype 2, potentially contributing to developing new therapeutic approaches for dengue. Full article

Background: Periodontitis and diabetes mellitus (DM) exhibit a bidirectional relationship and are globally significant systemic chronic conditions. The utilization of antibiotics alongside non-surgical periodontal treatment (NSPT) has been a subject of investigation in numerous clinical studies involving human subjects. Thus, the objective of this systematic review is to address the following question: “What is the efficacy of scaling and root planing (SRP) associated with antimicrobials in patients with type 2 DM and periodontitis?”. Methods: A systematic review of the literature was conducted encompassing databases such as MEDLINE/PubMed, Scopus, and Web of Science up to July 2024. Additionally, alerts were configured to capture studies published from the initial search until manuscript submission. Randomized clinical trials assessing clinical periodontal parameters in DM patients undergoing SRP and receiving either topical or systemic antibiotics were compared against a control group (SRP only). Two investigators independently screened articles, extracted data, and evaluated their quality. The selection process, study characteristics, risk of bias, impact of antibiotics on clinical parameters, and certainty of evidence were elucidated in both textual and tabular formats. Meta-analysis was performed separately with forest plots generated for treatment modalities, period of evaluation, and type of antibiotics used. Results: Following the analysis of abstracts and full articles, a total of 30 randomized clinical trials were incorporated into this review, comprising 9 studies on the association of topical antibiotics and 21 studies on systemic antibiotic administration. The principal periodontal parameters assessed included probing pocket depth (PPD), clinical attachment level (CAL), plaque index (PI), and bleeding on probing (BoP). Conclusions: Analysis of the results led to the conclusion that adjunctive periodontal treatment with either topical or systemic antibiotics confers subtle clinical benefits. Nevertheless, owing to the heightened emergence of resistant bacteria and potential side effects, the use of antibiotic therapy in periodontal treatment should be judiciously administered. Full article