Search Results (95)

Background and Objectives: Diabetes mellitus (DM) significantly impacts post-surgical recovery and fracture healing; however, few studies have specifically investigated the impact of DM on outcomes in patients undergoing surgical stabilization of rib fractures (SSRF). This study investigated the potential influence of DM on perioperative outcomes following SSRF, using data from Taiwan’s National Health Insurance Research Database (NHIRD). Materials and Methods: Data of 1603 patients with multiple rib fractures who underwent SSRF between 2001 and 2019 were retrospectively analyzed. Patients were categorized into three groups: no DM, DM without chronic complications, and DM with chronic complications. The associations between DM status and perioperative outcomes, including hospital length of stay (LOS), in-hospital mortality, readmission rates, and complications such as pneumonia, surgical site infection (SSI), acute myocardial infarction (AMI), and total hospital costs were determined using univariate and multivariable regression analyses. Results: The mean age of the 1603 patients was 52.0 years, and 71% were male. Patients with DM and chronic complications had higher risks of 14-day readmission (adjusted odds ratio [aOR] = 2.99; 95% confidence interval [CI]: 1.18–7.62), 15–30 day readmission (aOR = 3.28; 95% CI: 1.25–8.60), SSI (aOR = 2.90; 95% CI: 1.37–6.14), AMI (aOR = 3.44; 95% CI: 1.28–9.24), and acute respiratory distress syndrome (ARDS) (aOR = 1.96; 95% CI: 1.03–3.74). In conclusion, DM, particularly DM with chronic complications, significantly increases the risk of adverse short-term outcomes following SSRF. Conclusions: These findings emphasize the need for enhanced care for patients with DM to optimize the outcomes of SSRF. Full article

Despite significant advances in understanding and management, cardiovascular diseases remain the leading cause of mortality worldwide. Historically, diagnostic and therapeutic strategies have typically targeted obstructive coronary arteries. However, growing evidence supports the pivotal role of non-obstructive mechanisms in myocardial ischemia, prompting a new classification that distinguishes Acute Myocardial Ischemic Syndromes from Non-Acute Myocardial Ischemic Syndromes. In this evolving context, Optical Coherence Tomography (OCT) plays an important diagnostic role in the assessment of both obstructive and non-obstructive ischemic mechanisms. In Acute Myocardial Ischemic Syndromes, OCT enables the identification of major plaque destabilization mechanisms and contributes to the diagnosis of Myocardial Infarction with Non-Obstructive Coronary Arteries, helping to differentiate between atherosclerotic and non-atherosclerotic causes. In Non-Acute Myocardial Ischemic Syndromes, OCT assists in evaluating stenosis severity, plaque morphology, vulnerability, and healing, and may contribute to the diagnosis of Ischemia with Non-Obstructive Coronary Arteries, identifying myocardial bridge and epicardial spasm alongside conventional functional assessment of intermediate stenoses. This narrative review outlines the expanding clinical applications of OCT across the full spectrum of ischemic syndromes, emphasizing its role in bridging obstructive and non-obstructive pathophysiology and supporting a more comprehensive diagnostic approach to ischemic heart disease. Full article

Background/Objectives: Fibroblast activation protein (FAP) has gained tremendous traction as a target for tumor imaging and cancer treatment, while also playing a key role in fibrosis. Our study aimed to evaluate [⁶⁸Ga]Ga-DATA^5m.SA.FAPi for PET imaging of replacement fibrosis following myocardial infarction (MI) or interstitial fibrosis associated with hypertrophy. Methods: MI or transverse aortic constriction (TAC)-induced hypertrophy was induced in C57BL/6 mice, with sham-operated animals serving as controls. At multiple time points during disease progression (1, 2, and 6 weeks post-surgery), [⁶⁸Ga]Ga-DATA^5m.SA.FAPi PET/CT scans were performed, followed by ex vivo investigations. Additionally, in vitro cell uptake experiments simulating hypertrophy were conducted. Results: Cardiac uptake of [⁶⁸Ga]Ga-DATA5m.SA.FAPi significantly increased two weeks after MI induction (MI: 2.1 ± 0.2%ID/g, n = 7 vs. SHAM: 1.1 ± 0.2%ID/g, n = 5; p = 0.002), confirmed by ex vivo autoradiography. No significant difference was observed at six weeks post-MI (MI: 1.1 ± 0.1%ID/g, n = 4 vs. SHAM: 0.8 ± 0.0%ID/g, n = 3), indicating infarct healing completion. In contrast, TAC mice showed increased uptake after six weeks (TAC: 1.8 ± 0.2%ID/g, n = 6; p = 0.007), related to interstitial fibrosis progression. Consistently, high-stretched cardiac fibroblasts demonstrated a higher uptake compared to low-stretched conditioned ones, suggesting the stretch mediates regulation of FAP. Conclusions: This study demonstrated the efficacy of [⁶⁸Ga]Ga-DATA^5m.SA.FAPi for longitudinal imaging of cardiac fibrosis in response to different cardiac injuries. In vivo FAP imaging during cardiac remodeling may serve as a valuable tool for diagnosing and predicting disease progression, ultimately aiding in the clinical management of patients. Full article

Regenerative medicine is a challenging field in current research and development, whilst translating the findings of novel tissue regenerative agents into clinical application. Protein-based hydrogels are derived from various sources, with animal-derived products being primarily utilized to deliver cells and promote cell genesis and proliferation, thereby aiding in numerous indications, including bone tissue regeneration, cartilage regeneration, spinal cord injury, and wound healing. As biocompatible and biodegradable systems, they are tolerated by the human body, allowing them to exert their beneficial effects in many indications. In this review article, multiple types of animal-derived proteins (e.g., collagen, gelatin, serum albumin, fibrin) were described, and a selection of the recent literature was collected to support the claims behind these innovative systems. During the literature review, special indications were found when applying these hydrogels, including the therapeutic option to treat post-myocardial infarct sites, glaucoma, and others. Maintaining their structure and mechanical integrity is still challenging. It is usually solved by adding (semi)synthetic polymers or small molecules to strengthen or loosen the mechanical stress in the hydrogel’s structure. All in all, this review points out the potential application of value-added delivery systems in regenerative medicine. Full article

Background: Fibroblast activation protein (FAP) is a cell surface glycoprotein expressed by myofibroblastic cells in areas of active tissue remodeling, such as wound healing, fibrosis, and certain chronic inflammatory lesions. As FAP is uniquely present in chronic inflammatory lesions and has an important role in extracellular matrix (ECM) turnover, it appears to have all the characteristics necessary for involvement in atherosclerosis and atherosclerotic plaque rupture and has become a potential target in the treatment of myocardial infarction. Methods: To further understand the role of FAP, its expression in atherosclerotic plaques was examined in a genetically modified mouse model of accelerated atherosclerosis (Apobec1 −/− Ldlr −/− double-knockout mice). The immunohistochemical Fap staining of atherosclerotic plaques in a mouse model of atherosclerosis was correlated with quantification of Fap mRNA obtained from the atherosclerotic plaques of the aortic arch. Fap distribution was characterized in mouse atherosclerotic plaques relative to other markers of activated smooth muscle cells, such as alpha smooth muscle actin and myosin heavy chain (Acta2 and Myh2), ECM turnover (Ki-67, procollagen III and Mmp-9), and inflammation in atherosclerosis (Cd-44, Il-12 and Tgf beta) using immunohistochemistry (IH) and RT-PCR analysis. Results: The mouse model of accelerated atherosclerosis showed an increasing presence of Fap with the progression of atherosclerosis and a high expression level in advanced atherosclerotic lesions compared with other markers of ECM turnover and inflammation in atherosclerosis. Conclusions: FAP exhibits a distinct pattern of expression in a mouse model of atherosclerosis as compared to other markers of activated vascular smooth muscle cells, ECM degeneration, and inflammatory cytokines. Full article

Acute coronary syndromes (ACS) are a leading cause of death and impairment in the adult population. Precise identification and modification of risk factors is crucial for a favorable clinical outcome. In this review, we aim to provide a comprehensive overview of the significance of iron deficiency (ID) in patients with ACS, particularly myocardial infarction (MI). The paper evaluates the impact of ID on the prognosis of ACS patients, highlighting its potential influence on myocardial healing, regeneration and cardiovascular events during the follow-up period. The findings suggest that iron deficiency may have a negative impact on the prognosis of patients with MI, resulting in worse quality of life, physical capacity and higher rehospitalization rates in comparison to patients with normal iron status. Iron supplementation in patients with MI could be beneficial and may have an effect on myocardial healing and left ventricular remodeling. Full article

Background: Ischemic heart disease remains the leading cause of death worldwide, with coronary microvascular dysfunction (CMD) as a key complication after ST-elevation myocardial infarction (STEMI). Endothelial dysfunction contributes to CMD, impairing vascular tone and increasing inflammation. While angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) aid vascular health, their efficacy may improve with therapeutic ultrasound, which enhances drug delivery and endothelial response. This study explores the combined effects of ultrasound and pharmacological treatment on the ACE axis and inflammation in endothelial and renal cells. Methods: Human umbilical vein endothelial cells (HUVECs) and human renal proximal tubular epithelial cell line RPTEC/TERT1 were treated with captopril, losartan, and dexamethasone, alone or combined with low-frequency ultrasound (LFU). Cell viability and wound-healing assays assessed cellular function, while nitric oxide (NO) and reactive oxygen species (ROS) assays were used to evaluate redox signaling. Gene expression related to the ACE axis, inflammation, and vascular and renal cell function was analyzed via qPCR. Results: Captopril and losartan combined with LFU improved endothelial cell viability, wound healing, and NO production at various concentrations, whereas only losartan with LFU enhanced cell viability and wound healing in renal cells. Dexamethasone with LFU increased ROS levels and had variable effects on RPTEC/TERT1 cell survival. Gene expression analysis showed that LFU alone reduced pro-inflammatory markers VCAM-1, ICAM-1, and PTGS2 in captopril-treated HUVECs and similarly affected CYP4F2 in losartan-treated HUVECs. LFU also decreased PTGS2 expression at higher dexamethasone concentrations. In RPTEC/TERT1 cells, LFU alone did not impact SGLT2 or GGT1 expression, but captopril with LFU downregulated GGT1, and dexamethasone with LFU upregulated SGLT2 at higher concentrations. Conclusions: This study demonstrates that LFU enhances the effects of RAS inhibitors by promoting NO synthesis and reducing oxidative stress, while its combination with dexamethasone may have variable, potentially cytotoxic effects on renal cells. Gene expression patterns suggest LFU’s anti-inflammatory potential and its role in modulating drug efficacy. Full article

Heart failure functions as one of the leading global causes of death because it falls under the cardiovascular disease categories. Cardiac tissue engineering advances by developing new tissues to rebuild heart functions in individuals with damaged heart structures as it gives medical treatment possibilities to patients reaching their final stage. Most of the heart tissue consists of cardiomyocytes which make up between 80 to 90 percent of the total organ space. The cardiomyocytes retain their specialized cell structure which includes elongation, but they align to produce contractions as they span into length. After myocardial infarction, doctors need elastic soft platforms to heal the heart tissue because they mimic its natural attributes. Special consideration must be paid to the material selection for appropriate mechanical properties, given that different substances have separate qualities. Stem cell survival becomes higher, and cell differentiation develops more efficiently when a proper scaffold design is implemented, thus enabling tissue repair. Conductive biomaterials demonstrate the best candidate status for cardiac tissue engineering due to their ability to both convey electrical signals and boost biological actions as well as promote cellular communication. Scientists conduct life science research on stem cells because the cells present unique characteristics. Biomaterials with conductive properties within cardiac tissue engineering help the body recover heart tissue while improving the functionality of damaged structures in the myocardium. This article analyzes various conductive biomaterials used in biomedical practices for cardiac tissue healing applications. Full article

Mesenchymal stem cells (MSCs) have emerged as a promising tool for regenerative medicine due to their multipotency and immunomodulatory properties. According to recent research, exposing MSCs to super-low-intensity microwave radiation can have a significant impact on how they behave and operate. This review provides an overview of the most recent studies on the effects of microwave radiation on MSCs with power densities that are much below thermal values. Studies repeatedly show that non-thermal mechanisms affecting calcium signaling, membrane transport, mitochondrial activity, along ion channel activation may increase MSC proliferation, differentiation along mesodermal lineages, paracrine factor secretion, and immunomodulatory capabilities during brief, regulated microwave exposures. These bioeffects greatly enhance MSC regeneration capability in preclinical models of myocardial infarction, osteoarthritis, brain damage, and other diseases. Additional study to understand microwave treatment settings, biological processes, and safety assessments will aid in the translation of this unique, non-invasive strategy of activating MSCs with microwave radiation to improve cell engraftment, survival, and tissue healing results. Microwave-enhanced MSC treatment, if shown safe and successful, might have broad relevance as a novel cell-based approach for a variety of regenerative medicine applications. Full article

Background: Our recent findings, of the highest survival rate of animals that consumed moderate amounts of white wine for four weeks prior to surgically induced myocardial infarction by the ligation of the left anterior descending artery, prompted us to investigate the inflammatory aspects of the post-infarction healing process. In order to examine whether the effects of wine consumption differ from that of ethanol, experimental animals were randomized into three groups: white wine, 13% v/v ethanol/water or water-only controls. Methods: Hearts for immunohistochemical analysis were collected from animals that survived 96 h after infarction, consumed no less than 8 mL of white wine or ethanol/water solution per day and had transmural infarcts of comparable sizes. After accounting for all of the above criteria, the final number of animals was seven per group. Tissue slices were stained with a pan-macrophage marker CD68 and an anti-inflammatory macrophage marker CD163 to investigate macrophage polarization that is crucial for the inflammatory aspects of post-infarction healing. Immunofluorescent imaging was performed on four zones surrounding the infarcted area with detritus: subepicardial, subendocardial and two peri-infarct zones. Results: The largest CD163/CD68 ratios for comparable volumes of alcohol consumption were observed in the wine group in all zones. CD163/CD68 ratios decreased in both the ethanol and wine group as the average amount of alcoholic beverage consumed by the animals increased. Conclusions: Our results indicate that non-alcoholic constituents of white wine contribute to its superior effects in the favorable modulation of post-infarction inflammation and healing processes relative to that of ethanol alone. Full article

Immuno-fibrotic networks and their protein mediators, such as cytokines and chemokines, have increasingly been appreciated for their critical role in cardiac healing and fibrosis during cardiomyopathy. Immune activation, trafficking, and extravasation are tightly regulated to ensure a targeted and effective response against non-self antigens/pathogens while preserving tolerance towards self-antigens and coordinate fibrotic responses for efficient scar formation, a distinction that is severely compromised during chronic diseases. It is clear that immune cells are not only the critical regulators of post-infarct healing and scarring but are also the key players in regulating fibroblast activation during left-ventricular (LV) remodeling. Incomplete resolution coupled with sustained low-grade inflammation during dilated cardiomyopathy precipitates a “frustrated” immune cell response resulting in unconstrained pro-fibrotic and pro-hypertrophic signaling to induce maladaptive structural and functional changes in the myocardium. The aims of this review are to (i) briefly summarize the role of key immune cells that regulate wound healing during MI and fibrosis during LV remodeling; (ii) underscore phenotypic diversities in immune cells and their subsets to underscore their role in regulating fibrotic responses, and, last but not the least, (iii) highlight gaps in our understanding that restrict the translation of immuno-modulatory therapies from the preclinical models to heart failure patients. Full article

Background: Inflammation plays a critical role in myocardial infarction as a critical process in the development of heart failure, involving the development of cardiac fibrosis. Colchicine is a well-established anti-inflammatory drug, but its scientific application in controlling post-acute myocardial infarction (AMI) inflammatory processes has not been established. IL-10 is a key cytokine in modulating inflammatory responses, underscoring its potential as a crucial therapeutic target of colchicine. The objective was to explore the protective role of IL-10 modulated by colchicine in myocardial healing and repair following AMI, particularly cardiac fibrosis. Methods: The predicted protein of colchicine was assessed using WAY2DRUG PASS as probability active value. Proteins associated with colchicine, cardiac fibrosis, and acute myocardial infarction were analyzed with DisGeNET and Open Target databases. Analysis and visualization of protein–protein interactions were conducted using STRING and Cytoscape. A 3T3 cell line treated with CoCl₂ was used to mimic hypoxic. HIF-1α and IL-10 expression were measured by flow cytometry and analyzed using a one-way ANOVA test. This observational clinical trial examined acute myocardial infarction patients undergoing immediate and delayed primary percutaneous coronary interventions. Subjects were randomized into control groups receiving placebo and intervention groups treated with colchicine. Assessments occurred at 24 h and five days after the intervention. IL-10 expression in the clinical trial was measured by ELISA and analyzed using a T-test. Results: Colchicine demonstrates promising bioactivity in treating acute myocardial infarction, with notably activity values highlighting its probable role as a tubulin antagonist (0.744), beta-tubulin antagonist (0.673), and NOS2 inhibitor (0.529). Its primary action targets IL-10, with the protein–protein interactions analysis indicating interactions between IL-10 and key inflammatory mediators—IL-1β, IFN-γ, CCL2, TNF, and TGF-β1—during acute myocardial infarction and cardiac fibrosis. Hypoxic conditions in the CoCl₂-induced 3T3 cell model show significantly elevated HIF-1α compared to controls (p < 0.0001). Colchicine use significantly increased IL-10 expression in CoCl₂-treated cells (p < 0.0001) and in AMI patients within five days (p < 0.05). Conclusions: Colchicine may bolster the anti-inflammatory response post-myocardial infarction by activating IL-10 pathways in fibroblasts and in clinical settings, potentially reducing inflammation after AMI. Further investigation into broader aspects of this pathway, particularly in cardiac fibroblasts, is required. Full article

Ischemic heart disease, manifesting as myocardial infarction (MI), remains the leading cause of death in the western world. Both ischemia and reperfusion (I/R) cause myocardial injury and result in cardiac inflammatory responses. This sterile inflammation in the myocardium consists of multiple phases, involving cell death, tissue remodeling, healing, and scar formation, modulated by various cytokines, including the macrophage migration inhibitory factor (MIF). Meanwhile, different immune cells participate in these phases, with myeloid cells acting as first responders. They migrate to the injured myocardium and regulate the initial phase of inflammation. The MIF modulates the acute inflammatory response by affecting the metabolic profile and activity of myeloid cells. This review summarizes the role of the MIF in regulating myeloid cell subsets in MI and I/R injury and discusses emerging evidence of metabolism-directed cellular inflammatory responses. Based on the multifaceted role of the MIF affecting myeloid cells in MI or I/R, the MIF can be a therapeutic target to achieve metabolic balance under pathology and alleviate inflammation in the heart. Full article

Heart problems are quite prevalent worldwide. Cardiomyocytes and stem cells are two examples of the cells and supporting matrix that are used in the integrated process of cardiac tissue regeneration. The objective is to create innovative materials that can effectively replace or repair damaged cardiac muscle. One of the most effective and appealing 3D/4D scaffolds for creating an appropriate milieu for damaged tissue growth and healing is hydrogel. In order to successfully regenerate heart tissue, bioactive and biocompatible hydrogels are required to preserve cells in the infarcted region and to bid support for the restoration of myocardial wall stress, cell survival and function. Heart tissue engineering uses a variety of hydrogels, such as natural or synthetic polymeric hydrogels. This article provides a quick overview of the various hydrogel types employed in cardiac tissue engineering. Their benefits and drawbacks are discussed. Hydrogel-based techniques for heart regeneration are also addressed, along with their clinical application and future in cardiac tissue engineering. Full article

Myocardial infarction (MI) sets off a complex inflammatory cascade that is crucial for effective cardiac healing and scar formation. Yet, if this response becomes excessive or uncontrolled, it can lead to cardiovascular complications. This review aims to provide a comprehensive overview of the tightly regulated local inflammatory response triggered in the early post-MI phase involving cardiomyocytes, (myo)fibroblasts, endothelial cells, and infiltrating immune cells. Next, we explore how the bone marrow and extramedullary hematopoiesis (such as in the spleen) contribute to sustaining immune cell supply at a cardiac level. Lastly, we discuss recent findings on how metabolic cardiovascular risk factors, including hypercholesterolemia, hypertriglyceridemia, diabetes, and hypertension, disrupt this immunological response and explore the potential modulatory effects of lifestyle habits and pharmacological interventions. Understanding how different metabolic risk factors influence the inflammatory response triggered by MI and unraveling the underlying molecular and cellular mechanisms may pave the way for developing personalized therapeutic approaches based on the patient’s metabolic profile. Similarly, delving deeper into the impact of lifestyle modifications on the inflammatory response post-MI is crucial. These insights may enable the adoption of more effective strategies to manage post-MI inflammation and improve cardiovascular health outcomes in a holistic manner. Full article