Inflammatory Infiltration Research Articles

Artesunate Alleviates Chronic Hyperoxia-induced Bronchopulmonary Dysplasia by Suppressing NF-κB Pathway in Neonatal Mice.

Bronchopulmonary dysplasia (BPD) is a chronic lung condition that occurs in premature infants who undergo prolonged mechanical ventilation and oxygen therapy. Existing treatment methods have shown limited efficacy, highlighting the urgent need for new therapeutic strategies. Artesunate (AS) is a compound known for its potential anti-inflammatory properties, and studies have shown its protective effects against acute lung injury. However, its impact on BPD and the underlying mechanisms remain unclear. To investigate the effect and underlying mechanism of AS on chronic hyperoxiainduced BPD in neonatal mice. Full-term C57BL/6J mice were randomly assigned to the Air+lactate Ringer's solution (L/R) group, O2 + L/R group, and O2 + AS group. Analysis was performed using assay methods such as ELISA, RT-qPCR, hematoxylin-eosin staining, and Western blotting. Compared with the O2+L/R group, the expression of inflammatory factors in the serum, tissue, and BALF of the O2+AS group was significantly reduced, the lung function of the mice was improved, and the inflammatory infiltrates were significantly alleviated. AS inhibited the mRNA expression of inflammatory factors in mice. We found that the expression of nuclear p65 and cytoplasmic p-IκBα in the NF-κB pathway was inhibited after adding AS. AS ameliorated chronic hyperoxia-induced BPD in neonatal mice probably by inhibiting the expression of NF-κB pathway and inflammatory factors.

Mesenchymal Stem Cell-conditioned Medium Protecting Renal Tubular Epithelial Cells by Inhibiting Hypoxia-inducible Factor-1α and Nuclear Receptor Coactivator-1.

Acute kidney injury (AKI) is characterized by inflammatory infiltration and damage and death of renal tubular epithelial cells (RTECs), in which hypoxia plays an important role. Deferoxamine (DFO) is a well-accepted chemical hypoxia-mimetic agent. Mesenchymal stem cell-conditioned medium (MSC-CM) can reduce local inflammation and repair tissue. In this study, we explored the effect and molecular mechanism of MSC-CM-mediated protection of RTECs under DFO-induced hypoxia. Rat renal proximal tubule NRK-52E cells were treated with different concentrations of DFO for 24 hours, followed by evaluation of RTEC injury, using a Cell Counting Kit-8 (CCK-8) to detect cell viability and western blotting to evaluate the expression of transforming growth factor- beta 1 (TGF-β1), α-smooth muscle actin (α-SMA), and hypoxia-inducible factor-1 alpha (HIF-1α) in NRK-52E cells. Then, three groups of NRK-52E cells were used in experiments, including normal control (NC), 25 μM DFO, and 25 μM DFO + MSC-CM. MSC-CM was obtained from the human umbilical cord. MSC-CM was used to culture cells for 12 hours before DFO treatment, then fresh MSC-CM and 25 μM DFO were added, and cells were cultured for another 24 hours before analysis. Western blotting and cellular immunofluorescence staining showed culture of NRK-52E cells in 25 μM DFO for 24 hours induced HIF-1α and nuclear receptor coactivator-1 (NCoA-1), simulating hypoxia. MSC-CM could inhibit the DFO-induced up-regulation of α-SMA, TGF-β1, HIF-1α and NCoA-1. Our results suggest that MSC-CM has a protective effect on RTECs by down-regulating HIF-1α and NCoA-1, which may be the harmful factors in renal injury.

Evaluation of the Safety and Efficacy of Curcumin-Synthesized Silver Nanoparticles in Rats Exposed to Chlorpyrifos During Puberty Development.

Silver nanoparticles (Ag-NPs) have garnered significant attention in recent years due to their therapeutic effects. Curcumin (CUR) has been utilized as a coating agent for synthesizing Ag-NPs, intended to act as a potential drug. This study was designed to evaluate the safety and efficacy of curcuminsynthesized silver nanoparticles on rats exposed to chlorpyrifos (CPF) during their pubertal development. Forty-two male Wistar rats, 23 days old, were selected and randomly divided into 7 groups (n=6) as follows: positive control, negative control, CPF (5 mg/kg), silver nanoparticles synthesized using curcumin at 40 μg/kg (CUR-Ag-NPs 40), CUR-Ag-NPs 80, CPF+ CUR-Ag-NPs 40, CPF+ CUR-AgNPs 80. All treatments were administered via gavage for 30 days. At the end of the study, rats were anesthetized using ketamine (50 mg/kg), and xylazine, (10 mg/kg) and blood was collected from the heart for serum analysis of liver enzymes, urea, and creatinine. Liver and kidney tissues were isolated for histopathological analysis. No significant differences were observed in serum levels of AST, ALT, and ALP enzymes as well as urea and creatinine levels among the different groups. Light microscopy observation revealed multifocal inflammatory mononuclear cell subsets in liver tissue associated with mild inflammatory mononuclear cell infiltration in the portal region in CPF, CUR-Ag-NPs 40, CUR-Ag-NPs 80, CPF+CUR-Ag-NPs 40, and CPF+CUR-Ag- NPs 80 groups. Histological examination of kidney tissue showed degenerative changes in the tubular epithelium, congestion, and mild infiltration of mononuclear inflammatory cells in the renal interstitial tissue in the CPF group, CUR-Ag-NPs 40, CUR-Ag-NPs 80, CPF+CUR-Ag-NPs 40 and CPF+CUR-Ag-NPs 80 groups. This study failed to establish the safety and efficacy of CUR-Ag-NP at 40 and 80 μg/kg in prepubertal rats exposed to CPF. However, further studies should be conducted to thoroughly characterize the efficacy of CUR-Ag-NP in developmental animal models.

Plastic bronchitis associated with human bocavirus 1 infection in children.

Plastic bronchitis (PB) is a clinical-pathological syndrome characterized by the abnormal accumulation of endogenous substances in the bronchial airways, causing partial or complete obstruction and resulting in impaired lung ventilation. In this retrospective analysis, we aim to summarize the clinical manifestations, imaging characteristics, diagnostic methods, and treatment approaches to enhance clinicians' ability to detect children who are infected withhuman bocavirus 1(hBoV 1) and develop PB. In the period from January 2021 to January 2024, a total of six hBoV 1 infection children were diagnosed with PB through bronchoscopy. The onset of the condition was mainly concentrated between June and December. The detection methods used included metagenomic next-generation sequencing for pathogen identification (three cases) and respiratory pathogen nucleic acid 13-plex detection (oropharyngeal swab) (three cases), both of which confirmed the presence of hBoV 1. Out of the six children with PB, two were girls and four were boys. Their ages ranged from 10 months to 4 years old. Common symptoms reported by all patients included fever, cough,and wheezing. Chest high-resolution computed tomography scans revealed atelectasis in six cases, in addition to pneumonia. After the removal of the plastic bronchi via bronchoscopy, the airway obstruction symptoms in the children were relieved, and no recurrence was observed during the follow-up period. Pathological findings indicated cellulose exudation and inflammatory cell infiltration, consistent with nonlymphatic PB. When children infected with hBoV 1 exhibit persistent or worsening symptoms such as cough, fever, and wheezing despite treatment, clinicians should remain highly vigilant for the potential occurrence of PB. Bronchoscopy plays a crucial role not only in diagnosing the presence of a plastic bronchus but also in effectively treating PB.

Diabetes mellitus exacerbates inflammation in a murine model of ligature-induced peri-implantitis: A histological and microtomographic study.

To investigate the influence of diabetes mellitus (DM) in a murine model of peri-implantitis (PI). Twenty-seven 4-week-old C57BL/6J male mice had their first and second maxillary left molars extracted. Eight weeks later, one machined implant was placed in each mouse. Four weeks after osseointegration, the mice were divided into three groups: (a) control (C), (b) PI and (c) DM + PI. DM was induced by streptozotocin (STZ) administration. After DM induction, PI was induced using ligatures for 2 weeks. The hemimaxillae were collected for micro-CT and histological analyses. The primary outcomes consisted of linear (mm) and volumetric (mm3) bone loss. Secondary outcomes were based on histological analysis and included inflammatory infiltrate, osteoclastic activity, matrix organization, composition and remodelling. Data are presented as means ± SEM. Statistical analyses were performed using one-way ANOVA, followed by Tukey's test. Gingival tissue oedema was detected in the PI and DM + PI groups. Micro-CT showed significantly increased linear and volumetric bone loss in the DM + PI group compared to the C and PI groups. H&E staining showed greater inflammatory response and bone resorption in the PI and DM + PI groups than in the C group. The DM + PI group had significantly higher osteoclast numbers than the C and PI groups. Picrosirius red stained less for types I and III collagen in the PI and DM + PI groups than in the C group. There was a significant increase in monocyte/macrophage (CD-11b) counts and matrix metalloproteinases (MMP-2 and MMP-8) marker levels and a significant decrease in the matrix metalloproteinases inhibition marker (TIMP-2) levels in the DM + PI group compared to the C and PI groups. DM exacerbates PI-induced soft-tissue inflammation, matrix degradation and bone loss.

Novel TBC1D8B variant causes neonatal nephrotic syndrome combined with acute kidney injury

BackgroundNephrotic syndrome (NPHS), characterized by proteinuria, hypoalbuminemia, and edema, can be caused by genetic variations. TBC1D8B was recently discovered as a novel disease-causing gene for X-linked NPHS. With only a few reported cases, the clinical manifestations associated with variants of this gene need to be further examined.MethodsWe recruited a newborn with NPHS complicated by acute kidney injury (AKI) and his parents and tested the potential genetic cause of the disease through trio-whole exome sequencing and Sanger sequencing. Western blotting (WB) was performed using a mutant plasmid to evaluate mutant protein expression levels. Since the TBC1D8B protein interacts with RAB proteins to catalyze the GTPase hydrolysis process, immunofluorescence (IF) can be used to verify the interaction between the TBC1D8B mutant protein and RAB11A/RAB11B, and thus to confirm its effect on the endocytosis and vesicle recycling functions of RAB proteins within the cell.ResultsThe child, at 1 month, showed severe edema and proteinuria and unexplained coma with epilepsy. Ultrasound examination revealed multiple organ enlargement, and MRI showed nonspecific high diffusion-weighted imaging signal characteristics in the splenium of the corpus callosum. Hematoxylin and eosin staining showed diffuse inflammatory cell infiltration in the renal interstitium and multifocal renal tubule lumen expansion. Diffuse fusion of podocyte foot processes was observed under electron microscopy, indicating glomerular podocyte lesions. Genetic testing revealed a maternally inherited novel hemizygous variant, NM_017752: c.628 A > T, p.Lys210Ter, in TBC1D8B. In vitro functional experiments showed that this variant may lead to TBC1D8B protein degradation. IF results showed disrupted interaction with RAB11A/RAB11B, that then affects the biological function of RAB proteins in the process of cell intimal vesicle formation and intracellular transport.ConclusionThis study will enrich the mutational and phenotypic spectra of TBC1D8B and demonstrate the potential of this gene variants to cause early-onset NPHS leading to severe kidney disease.

Etomidate Inhibits Hepatic Ischemia-Reperfusion Injury Depending on the Activation of Nrf2-HO-1 Signaling Pathway.

Hepatic ischemia-reperfusion (I/R) injury (HIRI) is recognized as a local aseptic inflammatory response driven by innate immunity and is considered a leading cause of early organ dysfunction and failure following liver transplantation. Etomidate (Eto), an anesthetic drug known for its ability to inhibit inflammatory response and apoptosis, was the focus of our investigation. In this study, we conducted hepatic I/R surgery invivo on C57 mice, analyzing liver damage through histopathology. Additionally, primary hepatocytes isolated from mice were cultured and subjected to hypoxia/reoxygenation (H/R) insult in vitro, with cell activity assessed using the CCK8 assay and immunofluorescence staining employed to analyze liver inflammatory cell infiltration and apoptosis. Results showed that Eto effectively inhibited liver injury, inflammatory response, and apoptosis induced by HIRI surgery, with the greatest effect observed at an Eto concentration of 10 mg/kg. Furthermore, Eto also showed the ability to inhibit H/R-induced cell damage, inflammatory activation, and apoptosis in primary hepatocytes. Further mechanistic studies revealed that Eto could promote the activation of the Nrf2-HO-1 signaling pathway, and the protective effect of Eto on HIRI was nullified when the Nrf2 inhibitor ML385 was utilized. This study highlights the potential of Eto to protect against HIRI by promoting the Nrf2-HO-1 signaling axis.

Lactiplantibacillus plantarum NMGL2 exopolysaccharide ameliorates DSS-induced IBD in mice mainly by regulation of intestinal tight junction and NF-κB p65 protein expression

Treatment of inflammatory bowel disease (IBD), a common chronic intestinal disease, by exopolysaccharides (EPSs) produced by lactic acid bacteria has raised increasing concerns. Here, the EPS produced by Lactiplantibacillus plantarum NMGL2 was evaluated for its ameliorating effect on dextran sodium sulfate (DSS)-induced IBD in mice. Administration of the EPS was shown to decrease the body weight loss and the values of disease activity index (DAI) and alleviate the colon damage as evidenced by an improvement in colonic length shortening, a reduction in colonic coefficient, and a reduction in colonic mucosal architecture and inflammatory infiltration. Cytokine assay of the blood and colon tissue samples showed that the EPS could decrease the levels of pro-inflammatory TNF-α and IL-1β, and increase anti-inflammatory IL-10. Oxidative stress assay of the colon tissue showed that the nitric oxide (NO) and malondialdehyde (MDA) levels decreased significantly (p < 0.05), while superoxide dismutase (SOD) and glutathione (GSH) levels increased significantly (p < 0.05) after the EPS intervention. These results were further confirmed by the significantly (p < 0.05) down-regulated levels of NF-κB p65, p-IKKβ, and p-IκBα, and significantly (p < 0.05) enhanced expression of ZO-1 and occludin, as evaluated by Western-blot analysis of these proteins expressed in colonic tissue. The EPS produced by L. plantarum NMGL2 alleviated IBD by suppressing the NF-κB signaling pathway, suggesting its potential as a functional food agent in the prevention of IBD.

Supramolecular Self-Assembled Hydrogel for Antiviral Therapy through Glycyrrhizic Acid-Enhanced Zinc Absorption and Intracellular Accumulation.

Respiratory syncytial virus (RSV) is a common pathogen that causes respiratory infections in infants and children worldwide, significantly impacting hospitalization rates in this age group. Zinc ions are considered to have broad-spectrum antiviral potential against RNA viruses, including RSV. However, poor organism absorption and low intracellular accumulation of zinc require repeated high-dose supplementation, which may lead to unnecessary toxic side effects. In this research, a Zn2+-mediated glycyrrhizinic acid (GA)-based hydrogel (ZnGA Gel) was introduced and potentially developed to be a clinically available drug candidate for RSV therapy. ZnGA Gel was fabricated based on the cooperation of two potential RSV inhibiting molecules (Zn2+ and GA), where Zn2+ promoted self-assembly of GA and reduced its gel concentration and GA promoted zinc absorption and distribution in lung tissue in vivo. The facile construction of supramolecular hydrogel by the self-assembled coordination complex made it an injectable, temperature-sensitive, and pH-responsive controlled-release drug delivery for Zn2+. Most importantly, GA was observed to enhance organism absorption and intracellular accumulation of Zn2+ and was identified as a zinc ionophore for the first time. GA can colonize on the cell membrane and disturb cell membrane potential, resulting in an enhanced cell membrane permeability. In the presence of GA, more than 4.7-fold increasing Zn2+ concentrations materialized in the intracellular cytoplasm, compared to Zn2+ alone administration. This intracellular Zn2+ accumulation directly boosted the antiviral activities through improved inhibition of RSV replication-associated proteins and significantly inhibited RSV replication. Oral administration of ZnGA Gel on the RSV-infected mice model achieved an ideal therapeutic effect by effectively lowering viral load in the lungs, alleviating lung injury symptoms, and reducing inflammatory cell infiltration at pathological sites. The mechanism involved the inhibition of RSV replication-related proteins, aligning with our in vitro results. Additionally, ZnGA Gel had demonstrated biocompatibility, and reasonable supplementation of zinc was acceptable and effective for infants and children in clinical practice. Hence, the ZnGA Gel developed by us holds promise as an effective anti-RSV medicine in the future.

Empagliflozin treatment pre- and post- acute myocardial infarction reduces no-reflow, inflammatory cell infiltration and infarct size while preserving cardiac function.

Abstract Background and aims Empagliflozin (EMPA) and other members of the family of sodium glucose co-transporter 2 inhibitors have demonstrated clinical benefit in terms of survival and rehospitalizations in heart failure. However, their effect on acute myocardial infarction (AMI) is still under investigation. Microvascular injury (MVI) and no-reflow are major determinants of myocardial infarct size (IS) and prognosis. We investigated EMPA’s cardioprotective potential in AMI in terms of no-reflow, MVI and IS emphasizing on a translational regimen with EMPA treatment after AMI. Methods In a first series of experiments, C57Bl6 male mice (n=10 per group) were randomized into 1) Sham, 2) Control-AMI and 3) EMPA-Pre-AMI (10mg/kg/day orally for 6 weeks) groups. Mice underwent 30 min ischemia (I) and 2h reperfusion (R) or sham operation. Cell sorting and 3’ mRNA sequencing were applied to identify the cell types that are transcriptionally affected by EMPA pretreatment in mice with AMI. In a second series of experiments, the protocol was repeated, and an additional group was added, EMPA-Post-AMI (n=8-11 mice per group) in which oral treatment was performed 1h after R. Assessment of no-reflow via thioflavin S staining and electron microscopy was performed at 48 h. The infiltration of inflammatory cells in the ischemic heart was examined via flow cytometry. IS and myocardial function were determined by cardiac magnetic resonance (CMR). Type-2 diabetes mellitus patients received insulin (n=18) or EMPA (n=24) within 2 months post-AMI. Endothelial glycocalyx and endothelial-related circulating markers were examined at 4 months and 12 months post-AMI. Results EMPA pretreatment reversed AMI-induced alterations in cardiac endothelial cells’ (ECs) transcriptome. As such, it promoted the expression of survival genes, reduced gene expression related to adhesion molecules and ECs matrix degradation. Conversely, EMPA pretreatment exerted minimal effects on cardiomyocyte and fibroblast transcriptome. In support of the effect of EMPA on ECs, EMPA-Pre-AMI and EMPA-Post-AMI groups significantly reduced no-reflow and MVI as indicated by electron microscopy and histology at 48h of R. Moreover, both EMPA treatment pre-AMI and post-AMI reduced the infiltration of inflammatory monocytes and neutrophils in the infarcted myocardium suggesting enhanced vascular integrity. Both EMPA-Pre-AMI and EMPA-Post-AMI reduced IS and preserved cardiac function defined by CMR. Patients receiving EMPA presented with improved endothelial glycocalyx thickness, % global longitudinal strain and preserved pulse wave velocity. Conclusions EMPA treatment either before or after AMI protects against MVI, reduces no-reflow and IS and preserves cardiac function. Our data support the use of EMPA after recanalization in patients with AMI to confer improvement of cardiovascular function.

Unraveling Marfan hearts: ultrastructural evidence for myocardial remodeling and cardiomyopathy

Abstract Background Despite improved life expectancy for patients with Marfan syndrome (MFS), significant morbidity and mortality persist. Although primarily attributed to aortic dissection and rupture, recent studies highlight the emerging role of arrhythmias and heart failure as additional contributors to morbidity and mortality in MFS. While severe valvular heart disease is an established cause of heart failure, there is a growing recognition of primary cardiomyopathy in patients with MFS. The mechanisms underlying cardiomyopathy in MFS remain poorly understood. Purpose This study aimed to reveal insights into the ultrastructural myocardial architecture in patients with MFS, thereby elucidating the role of cardiomyopathy in MFS. Methods This study enrolled 44 patients who underwent cardiac surgery at 2 centers (Marfan syndrome patients n=27 (MFS), ascending thoracic aortic aneurysm repair patients n=5 (non-MFS), patients post-orthotopic heart transplant n=12 (controls)). Myocardial biopsy samples were subjected to histopathological analysis using transmission electron microscopy and conventional histology. Results Conventional histological analysis revealed subtle abnormalities in the cardiomyocyte morphology of MFS patients, compared to non-MFS and controls. Overall, a slight increase in interstitial fibrosis and mild myocyte hypertrophy were observed in MFS patients. Ultrastructural examination of both MFS and non-MFS patients revealed significant structural remodeling and degenerative changes in the myocardium. These changes included: extensive myofibril lysis, compromised cell membrane integrity and nuclear chromatin condensation. Degenerative lesions were often accompanied by cytoplasmic debris, lysosomal residual bodies, autophagic vacuoles, and severe mitochondrial pathology. Dense accumulation of glycogen granules and lipofuscin was evident in areas of focal myofibril lysis. Notably, only MFS patients exhibited recruitment of granulocytes, including mast cells, eosinophils and neutrophils. A subset of MFS patients displayed advanced stages of myocardial degeneration. However, these changes did not correlate with clinical myocardial failure. Conclusions To the best of our knowledge, this study represents the first evidence of ultrastructural changes in the myocardium of patients with MFS. Our data indicate various degenerative changes in the myocardial architecture, including structural and metabolic myocardial remodeling, along with inflammatory cell infiltration. We believe that our findings of ultrastructural lesions reflect the complexity of myocardial disease in MFS and emphasize the importance of careful surveillance for cardiomyopathy in MFS patients. Further studies are warranted to confirm whether the observed granulocyte influx is specific to MFS and to clarify its role in MFS myocardial disease pathophysiology.Graphical abstract

Neutrophil-Mimetic Upconversion Photosynthetic Nanosystem Derived from Microalgae for Targeted Treatment of Thromboembolic Stroke.

Thromboembolic stroke constitutes the majority of brain strokes, resulting in elevated mortality and morbidity rates, as well as significant societal and economic burdens. Although intravenous thrombolysis serves as the standard clinical treatment, its narrow therapeutic window and the inflammatory response induced by tissue plasminogen activator (tPA) administration limit its efficacy. In the initial stages of stroke, the abrupt cessation of blood flow leads to an energy metabolism disorder, marked by a substantial decrease in adenosine triphosphate (ATP) and nicotinamide adenine dinucleotide phosphate (NADPH) levels, causing irreversible damage to neural cells. In this study, we introduce a neutrophil-mimetic, microalgae-derived upconversion photosynthetic nanosystem designed for targeted treatment of thromboembolic stroke. This system features upconversion nanoparticles coated with a thylakoid membrane and wrapped in an activated neutrophil membrane, further decorated with ROS-responsive thrombolytic tPA on its surface. The neutrophil-mimetic design facilitates high targeting specificity and accumulation at the thrombus site after intravenous administration. Upon exposure to elevated levels of reactive oxygen species (ROS) at the thrombus location, the nanosystem promptly demonstrated potent thrombolytic efficacy through the surface-modified tPA. Furthermore, near-infrared II (NIR-II) laser irradiation activated the generation of ATP and NADPH, which inhibited inflammatory cell infiltration, platelet activation, oxidative stress, and neuronal injury. This constructed nanoplatform not only showcases exceptional targeting efficiency at the stroke site and controllable release of the thrombolytic agent but also facilitates ATP/NADPH-mediated thrombolytic, anti-inflammatory, antioxidative stress, and neuroprotective effects. Additionally, it offers valuable insights into the potential therapeutic applications of microalgae-based derivatives in managing thromboembolic stroke.

Gradual hypertensive response in aortic alterations and myocardial inflammatory activation in progressing HFpEF in mice

Abstract Introduction Hypertension is the most common comorbidity in patients affected by heart failure with preserved ejection fraction (HFpEF). Early effects of pressure overload and its contribution to the gradual development of cardiac and vascular pathology leading to HFpEF are not well recognized, as patients are diagnosed when the disease has already advanced and show symptoms. Several hypertensive HFpEF mouse models possessing the hallmarks of the clinical-like phenotype are available. Nonetheless, initial and gradual pathological manifestations of hypertensive HFpEF have not been comprehensively described. Purpose This study aimed to investigate the gradual progression of HFpEF phenotype development in mice from the early manifestation of cardiac and vascular pathology to global cardiac dysfunction to multiorgan syndrome in response to hypertension. Methods Hypertensive HFpEF was induced by angiotensin II infusion in C57BL/6JOlaHsd 18-20-week-old male mice that were given low, moderate and high doses (0.5mg/kg/day - 1.5 mg/kg/day) subcutaneously for 4 weeks. Cardiac physiology and alterations in haemodynamics were assessed with echocardiography of heart and aorta, weekly ECG monitoring, and blood pressure measurements from the mouse tail. Extensive histology and immunohistochemistry analyses of cardiac tissue, microvasculature, lungs and kidneys were performed. Results In the low dose group, loss of aortic wall flexibility and presence of aortic root dilatation were detected. This group also demonstrated initiation of concentric remodelling process with the upsurge in macrophage infiltration in myocardium, but the signs of diastolic dysfunction were not yet present. The high dose group exhibited characteristic HFpEF features with diastolic dysfunction, left ventricular hypertrophy and fibrosis. Pathology in cardiac conduction system was noticed in all groups, with prominent ECG waveform abnormalities already on week one. However, only the high dose group experienced non-recovery in impulse propagation, accompanied by significant prolongation of ventricular depolarization. Conclusion This study demonstrates that change in aortic root dimensions and aortic wall dynamics are the first hypertension-sensitive alterations together with myocardial inflammatory cell infiltration that may contribute to myocardial remodelling and subsequent development of HFpEF and systemic effects. Hypertensive angiotensin II-induced HFpEF is a relevant mouse model, recapitulating not only hallmarks of cardiac pathology but also an extensive range of vascular and multiorgan alterations, demonstrating similarities with the clinical phenotype.

Long-term pulmonary repair in rat lungs after sublobar resection: electrocautery versus stapler methods.

We investigated and compared the long-term (6-month) histologic changes in a rat model of sublobar resection created using electrocautery or stapler techniques. Nine-week-old male rats were anesthetized and intubated; thoracotomy with sublobar resection was performed in the right middle lobe using electrocautery or stapler techniques. Histological examination was performed at 2, 4, 8, 12, and 24weeks post-surgery to assess long-term effects on lung tissue repair and morphologic changes. Lung expansion and alveolar epithelial cell proliferation were evaluated by measuring the mean linear intercept and counting the number of alveolar type I and II cells. The electrocautery group showed signs of lung self-repair at the resected area over time, with inflammatory cell infiltration followed by growth of vessels and bronchioles. Mesothelial cells covered the resected area by 2weeks; elastic fibers gradually connected from both sides by 24weeks. Lung expansion, measured by mean linear intercept, was initially small below the electrocautery resection area at 2weeks but recovered from 4 to 24weeks. The stapler group showed persistently small mean linear intercept over time. In the electrocautery group, the number of alveolar type II cells was higher just below the resection than in other areas from 2 to 24weeks, followed by alveolar type I cells (4 to 24weeks). The stapler group showed a transient alveolar type II cell increase at 2weeks. Compared to the stapler technique, electrocautery mayprovide advantages for postoperative lung repair by promoting lung expansion and alveolar epithelial cell proliferation.

Clinical characteristics of idiopathic inflammatory myopathies related to anti-SRP: a single center experience

Idiopathic inflammatory myopathy (IIM) with autoantibodies recognizing the signal recognition particle (SRP) is characterized by prominent proximal weakness, infrequent extramuscular involvement, dramatically elevated creatine kinase levels, and myofiber necrosis with few inflammatory cell infiltrates in muscle tissue. To enhance understanding of the clinically used diagnosis and treatment of this disease, this study presents a single-center experience and analysis of a Chinese cohort with anti-SRP IIM. The most recent European Neuromuscular Center criteria were used to include Anti-SRP IIM patients from September 2016 to November 2019. Prior to treatment initiation, all sera were collected for the detection of anti-SRP autoantibodies and other myositis-related autoantibodies. Muscle strength, concurrent autoimmune conditions, comorbidities like interstitial lung disease (ILD), treatment outcomes, and follow-up results were also documented. Univariate logistic regression was employed to determine factors affecting prognosis. Among 271 patients with IIM, we identified 23 (8.5%) patients with anti-SRP IIM. Lower limb muscle weakness was frequently more severe. Interstitial lung disease (ILD) was observed in 50% of anti-SRP IIM patients. The presence of ILD may serve as a predictor of a poor prognosis, as revealed by univariate logistic regression analysis (odds ratio, 3.8, 95% CI: 1.0-6.8, p = 0.05).This Chinese Anti-SRP IIM cohort from Hunan province seems to have higher incidences of ILD, and associated ILD may be a risk factor for a poor prognosis. To fully understand the specific role of the anti-SRP autoantibody in this unique subset with ILD, further research is necessary.

The diagnostic value of endomyocardial biopsy in the era of precision medicine: data from over 8,000 patients with comprehensive biopsy diagnostics

Abstract Background Endomyocardial biopsy (EMB) is an important diagnostic tool for evaluating various cardiac diseases such as myocarditis and storage disorders as well as for the monitoring heart transplant patients. Despite advances in non-invasive imaging techniques to characterize myocardial tissue, EMB remains the gold standard for definitive diagnosis and initiation of specific therapy. Here we report EMB laboratory results from over 8,000 patients and demonstrate the diagnostic utility of EMB. Methods and results We retrospectively reviewed EMB analyses performed at our institution. EMBs for monitoring graft rejection were not included in this study. Clinical data, suspected clinical diagnoses and EMB-based laboratory results were collected. Histopathological, immunohistochemical and molecular biology biopsy findings were recorded and reviewed for degree of concordance with clinical diagnosis. In total, EMBs from N=8,085 consecutive patients with unexplained heart failure were analyzed. The comprehensive EMB analysis revealed that N=616 (7.6%) patients had cardiac storage disease, most of whom had cardiac amyloidosis (N=606). N=357 (4.4%) patients were diagnosed with acute forms of myocarditis, including N=95 cases with active myocarditis, N=148 cases with giant cell myocarditis, N=95 cases with sarcoidosis and N=19 cases with eosinophilic myocarditis. A total of N=3,392 (42%) patients were found to have inflammatory heart disease such as inflammatory cardiomyopathy and borderline myocarditis, whereby a differentiation of the inflammatory infiltrates revealed considerable differences in the quality of inflammation. Viral genomes were found in the myocardium of N=6,072 (75%) patients, with treatment-relevant viral infections detected in N=2,015 (25%) cases. The remaining N=1,705 (21%) patients were diagnosed with other cardiomyopathies, including dilated cardiomyopathy (N=1,252), heart failure with preserved ejection fraction (N=325), hypertrophic cardiomyopathy (N=117) and arrhythmogenic right ventricular cardiomyopathy (N=11). Conclusions This retrospective study of over 8,000 patients with heart failure clearly shows that a definitive diagnosis is only possible with a comprehensive EMB diagnosis and leads to specific therapy in 79% of the cases. In the remaining 21% of patients, infectious and inflammatory causes could be excluded in order to initiate standard heart failure therapy. It is important to emphasize here that the quality of the inflammation and therapy-relevant viral infections cannot be detected with imaging techniques, which underlines the clinical-therapeutic importance of endomyocardial biopsy.

Relationship between epicardial adipose tissue and ventricular fibrillation in Brugada syndrome by cardiac computed tomography analysis

Abstract Background Fibrofatty changes in the myocardium of the right ventricular (RV) to right ventricular outflow tract (RVOT) in patients with Brugada syndrome (BrS) may contribute to ventricular conduction delay and ultimately in the development of ventricular fibrillation (VF). In patients with atrial fibrillation (AF), inflammatory infiltration of epicardial adipose tissue (EAT) into the atrial muscle, along with reduced quantity and quality of EAT, has been demonstrated to be associated with the development of AF. We hypothesized that EAT in the RVOT from the RV in patients with BrS may lead to organic abnormalities in the ventricular muscle, resulting in VF. Purpose The purpose of this study was to evaluate the quantity and quality of EAT in patients with BrS using cardiac computed tomography (CT) and to determine the relationship with the occurrence of VF. Methods We retrospectively evaluated 61 of 82 patients with BrS regularly followed in our outpatient clinic from January 2000 to December 2023, who underwent cardiac CT scans. Patients were divided into two groups: those with VF events during follow-up (VF event group) and those without events (VF non-event group). Patient background, various parameters, volume of epicardial adipose tissue (EAT), and CT values from cardiac CT scans were compared between the two groups. EAT volume and CT values were measured for the entire heart and four specific regions: right ventricle (RV-EAT), right ventricular outflow tract (RVOT) to pulmonary artery bifurcation (RVOT-EAT), left ventricle (LV-EAT), and the left coronary artery main trunk circumference (LV summit-EAT) were measured for four specific sites. Results Median age at first diagnosis of BrS was 43 years, 98% were male patients, 41 patients (71%) had symptomatic BrS, and 18 patients (31%) had a family history. During a median follow-up of 72 months (30-136 months), 22 patients (38%) had VF events, including 2 arrhythmic sudden deaths. The median time from diagnosis to the first VF event was 14.3 months (4.3-24.5 months). The VF event group had more overall EAT volume (98.3 cm3 [range: 77.4 to 120.3 cm3] vs. 70.1 cm3 [range: 53.8 to 98.0 cm3], P=0.02) and significantly more RV-EAT volume (18.4 cm3 [range: 11.5 to 28.0 cm3] vs. 11.0 cm3 [range: 7.9 to 18.3 cm3], P=0.008). The CT value of RV-EAT was significantly lower in the VF event group (-83.1±6.1 vs -78.0±6.2, P=0.003), although the RV-EAT/LV-EAT density ratio was not different between the two groups (1.01±0.05 vs 0.99±0.07, P=0.14). On the other hand, the density ratio of RVOT-EAT/LV-EAT was significantly lower in the VF event group (0.95±0.08 vs. 1.00±0.08, P=0.03). Conclusions EAT analysis via CT in patients with BrS revealed that those experiencing VF events during follow-up tended to exhibit greater RV-EAT volume, lower CT values of RV-EAT, and higher CT values of RVOT-EAT density. These findings suggest EAT involvement in VF occurrence in patients with BrS.

The Effect of Copper Nanoparticles on Liver Metabolism Depends on the Type of Dietary Fiber

Background/Objectives: A diet enriched with copper nanoparticles (CuNPs) exhibits a wide range of effects on liver metabolism, both positive and negative. Dietary fibers are the key components that may affect the absorption of minerals, including copper, and change their impact on organisms. Methods: Therefore, this study investigated whether and how supplementation with different sources of dietary fiber (cellulose, pectin, inulin, and psyllium) affects the function of CuNPs in the liver of male Wistar rats. Results: The results showed that CuNPs at different doses had varying effects on lipid metabolism and inflammation in the liver. Specifically, higher doses of CuNPs were associated with increased lipid accumulation and the activation of pro-inflammatory mechanisms. However, combining CuNPs with dietary fibers, such as psyllium and inulin, was beneficial in mitigating the effects of the examined nanoparticles, leading to reduced fat, cholesterol, and triglycerides in the liver. Combining psyllium with CuNPs showed the most substantial effect on liver metabolism and inflammation parameters. Furthermore, hepatic histology analyses showed that adding psyllium to the diet with CuNPs reduces changes associated with fat accumulation and mononuclear cell infiltration. The observed beneficial changes in the liver may have been related to a reduction in the gene expression level of sterol regulatory element-binding protein 1 and peroxisome proliferator-activated receptor gamma and cyclooxygenase-2. Conclusions: In conclusion, enriching the diet with dietary fibers such as psyllium can regulate the action of CuNPs, thereby improving lipid metabolism and reducing inflammation in the liver.

Effect of Electrical Stimulation of the Vagus Nerve on Inflammation in Rats With Spinal Cord Injury

ObjectiveThe purpose of this study was to assess the effect of electroacupuncture stimulation (EAS) of the vagus nerve on the inflammatory response in rat models of spinal cord injury (SCI). MethodsThe T10 SCI model in adult male Sprague Dawley rats was established using the modified Allen's method. The EAS group was treated with the therapy on the vagus nerve of rat ear nails, while the SCI group did not receive any EAS treatment. The degree of inflammatory infiltration was reflected by hematoxylin-eosin staining. The inflammatory cytokines in spinal cord tissues, cerebrospinal fluid inflammation, and peripheral blood were detected by enzyme-linked immunosorbent assay. Changes in astrocytes and microglia were assessed using an immunofluorescence assay. ResultsElectroacupuncture stimulation treatment inhibited inflammatory infiltration, as well as the concentrations of interleukin-6, interleukin-1β, tumor necrosis factor-α, astrocytes, and microglia at 1, 6, and 24 hours after 1 EAS treatment. Multiple EAS treatments had an obvious effect on SCI inflammation. ConclusionA single EAS treatment had a limited effect on inflammation, but multiple treatments had a significant inhibitory effect on inflammation.

Effect of Ethyl-Cyanoacrylate and Platelet-Rich Fibrin on Fresh Sockets of Rabbits Subjected to Anticoagulant Therapy

Objectives: There are no studies related to the use of PRF associated with cyanoacrylates in fresh post-extraction sockets. Thus, the aim of this study was to assess the effect of ethyl-cyanoacrylate combined with PRF in fresh sockets of rabbits subjected to anticoagulant therapy. Methods: Twelve adults rabbits were selected and premedicated with heparin 1 week before surgery to induce and simulate anticoagulant therapy. Upper and lower first premolars on the right side were extracted and then were divided into four groups of three animals each, with the groups distributed according to the type of intervention in the sockets (n = 6): (1) clot and suture (control); (2) PRF and suture; (3) clot and ethyl-cyanoacrylate; (4) PRF and ethyl-cyanoacrylate. At 12 weeks, the animals were sacrificed and the sockets were analyzed histologically and quantitatively. Total bone area, inflammation infiltrate, and adhesive remnants were assessed. Results: No remnants of adhesive were found in the samples. Groups 1 and 2 showed the highest bone area (G1 = 37.87% ± 17.86; G2 = 30.31 ± 9.36) with significant differences to those treated with ethyl-cyanoacrylate adhesive (G3 = 26.6% ± 11.82; G4 = 24.29% ± 6.25). Conclusions: The groups that used ethyl-cyanoacrylate as a closure method in sockets exhibited less bone area than the groups that used sutures. Both groups that used PRF as therapy did not show a significant improvement in bone healing at 12 weeks compared with the clot groups.