Efficiently directing differentiation and homing of mesenchymal stem cells to boost cartilage repair in osteoarthritis via a nanoparticle and peptide dual-engineering strategy.

Mesenchymal stem cells (MSCs) are expected to be useful therapeutics in osteoarthritis (OA), the most common joint disorder characterized by cartilage degradation. However, evidence is limited with regard to cartilage repair in clinical trials because of the uncontrolled differentiation and weak cartilage-targeting ability of MSCs after injection. To overcome these drawbacks, here we synthesized CuO@MSN nanoparticles (NPs) to deliver Sox9 plasmid DNA (favoring chondrogenesis) and recombinant protein Bmp7 (inhibiting hypertrophy). After taking up CuO@MSN/Sox9/Bmp7 (CSB NPs), the expressions of chondrogenic markers were enhanced while hypertrophic markers were decreased in response to these CSB-engineered MSCs. Moreover, a cartilage-targeted peptide (designated as peptide W) was conjugated onto the surface of MSCs via a click chemistry reaction, thereby prolonging the residence time of MSCs in both the knee joint cavity of mice and human-derived cartilage. In a surgery-induced OA mouse model, the NP and peptide dual-modified W-CSB-MSCs showed an enhancing therapeutic effect on cartilage repair in knee joints compared with other engineered MSCs after intra-articular injection. Most importantly, W-CSB-MSCs accelerated cartilage regeneration in damaged cartilage explants derived from OA patients. Thus, this new peptide and NPs dual engineering strategy shows potential for clinical applications to boost cartilage repair in OA using MSC therapy.

The Administration of Steroids and its Impact on Caspase-3 Expression in Pediatric Adenoid Hypertrophy.

Objective: Adenoid hypertrophy is a prevalent pediatric condition, often necessitating surgical intervention. Intranasal steroid administration shows promise as a conservative treatment, particularly by inducing apoptosis in adenoidal cells, leading to a reduction in adenoid size and inflammation. This study aims to characterize the expression profile of caspase-3 as an apoptotic inducer protein in inflammatory and epithelial adenoid tissues and explore its association with steroid administration. Methods: We performed immunohistochemical staining for caspase-3 proteins in adenoid tissues obtained from 51 pediatric patients aged between 2.5 and 12 years (mean age: 6.09 ± 2.1 years) who underwent adenoid surgery. A retrospective analysis of clinical data was conducted, categorizing participants into steroid treatment receivers (n = 25) and non-receivers (n = 26). Subsequently, the lymphoid inflammatory tissue and epithelial tissue from the adenoid were compared in terms of caspase-3 protein expression, and associated clinical variables were assessed. Results: Immunohistochemical analysis revealed significant caspase-3 expression in inflammatory tissues. The expression levels were scored, and no significant correlation was observed between inflammation and epithelium based on caspase-3 expression (correlation coefficient = 0.143; p > 0.05). Furthermore, demographic and clinical characteristics did not show a statistically significant difference in caspase-3 expression levels. Conclusion: Caspase-3 expression was significant in inflammatory adenoid tissue, but it showed no association with nasal steroid administration.

Diagnostic Complexities and Management of Gouty Arthritis With Suspected Seronegative Rheumatoid Arthritis and Malignancy in an Elderly Male.

Rheumatoid arthritis (RA) and gout are two distinct types of inflammatory arthritis with significant morbidity. While RA is characterized by autoimmune synovitis, gout is defined by the deposition of urate crystals. Diagnosing these conditions becomes particularly challenging in patients with negative serological markers for RA, compounded by the patient's advanced age and potential for malignancy. This case involves a 77-year-old male with chronic gout, hypertension, chronic atrial fibrillation on edoxaban, diastolic congestive heart failure, and chronic kidney disease stage 3B, presenting with left knee pain and limited mobility. Despite negative serology for RA (rheumatoid factor (RF) <20.0 IU/ml, anti-CCP2 antibodies 1.2 U/mL), the clinical presentation raised suspicion for RA. Imaging revealed significant synovial hypertrophy and multiple periarticular lesions suggestive of chronic gouty tophi rather than RA or malignancy. The patient was managed with allopurinol, prednisolone, and colchicine and referred to rheumatology for further evaluation. Approximately 30% of RA patients may present with negative serological markers, complicating the diagnosis. Differentiating RA from gout is crucial due to differences in management strategies. Imaging modalities such as MRI and CT are essential in identifying characteristic changes of both conditions, such as synovial hypertrophy in RA and tophi in gout. In elderly patients, the possibility of malignancy should also be considered. This case highlights the complexity of diagnosing gouty arthritis mimicking seronegative RA, especially in elderly patients where the risk of malignancy must be considered. It underscores the need for comprehensive clinical and imaging evaluations and personalized treatment plans in managing patients with multiple comorbidities.

Artemisia argyi mitigates doxorubicin-induced cardiotoxicity by inhibiting mitochondrial dysfunction through the IGF-IIR/Drp1/GATA4 signaling pathway.

Doxorubicin (DOX) is mostly utilized as a wide range of antitumor anthracycline to treat different cancers. The severe antagonistic impacts of DOX on cardiotoxicity constrain its clinical application. Many mechanisms are involved in cardiac toxicity induced by DOX in the human body. Mitochondria is a central part of fatty acid and glucose metabolism. Thus, impaired mitochondrial metabolism can increase heart failure risk, which can play a vital role in cardiomyocyte mitochondrial dysfunction. This study aimed to assess the possible cardioprotective effect of water-extracted Artemisia argyi (AA) against the side effect of DOX in H9c2 cells and whether these protective effects are mediated through IGF-IIR/Drp1/GATA4 signaling pathways. Although several studies proved that AA extract has benefits for various diseases, its cardiac effects have not yet been identified. The H9c2 cells were exposed to 1 µM to establish a model of cardiac toxicity. The results revealed that water-extracted AA could block the expression of IGF-IIR/calcineurin signaling pathways induced by DOX. Notably, our results also showed that AA treatment markedly attenuated Akt phosphorylation and cleaved caspase 3, and the nuclear translocation markers NFATC3 and p-GATA4. Using actin staining for hypertrophy, we determined that AA can reduce the effect of mitochondrial reactive oxygen species and cell size. These findings suggest that water-extracted AA could be a suitable candidate for preventing DOX-induced cardiac damage.

Recurrent atrial flutter after radiofrequency ablation for atrial fibrillation in a patient with hypertrophic obstructive cardiomyopathy undergoing repetitive transcoronary ablation of septal hypertrophy.

INTRODUCTION: We described the clinical characteristics of a patient with hypertrophic obstructive cardiomyopathy (HOCM) who had undergone transcoronary ablation of septal hypertrophy (TASH) twice and developed atrial flutter after radiofrequency ablation for atrial fibrillation (AF) due to pulmonary vein reconnection. This case of HOCM is unique because of its complex complications and multiple complex atrial arrhythmias. The treatment of HOCM was successful and the postoperative follow-up results was good. METHODS AND RESULTS: A 71-year-oldfemale, developed exertional dyspnea with palpitations 12 years ago, with a valid diagnosis of HOCM according to the echocardiography which showed an absolute increase in the interventricular septum thickness (22.8 mm). She underwent two rounds of TASH and only the second round was successful. During a visit due to recurrent palpitations, the patient was diagnosed with AF based on electrocardiographic examination. Circumferential pulmonary vein isolation (CPVI) was performed to treat AF. However, the recurrence of atrial flutter was detected on her electrocardiograms (ECGs) three years after the operation. Since the patient had an interstitial lung injury, there were relative contraindications for antiarrhythmic drugs. Due to restrictive use of antiarrhythmic drugs and continuous palpitation, the patient agreed to receive a second radiofrequency ablation. Left-sided macroreentrant circuits were identified via high-density mapping and successful ablation was performed at the isthmus. CONCLUSIONS: Performing catheter ablation and TASH respectively in patients with HOCM associated with AF would be tricky. But taking such a comprehensive and respective clinical treatment would be beneficial to patients in the long term.

Congenital Vomer Agenesis: A Case Report From Saudi Arabia.

The nasal septum consists of the quadrangular septal cartilage, the maxillary and palatine bone crests, the perpendicular plate of the ethmoid bone, and the vomer. Congenital agenesis of the vomer is a rare condition. This case involves a 29-year-old male who presented to our clinic with alternating bilateral nasal obstruction and no history of allergic symptoms. Examination revealed clear bilateral osteomeatal complexes without polyposis or discharge. A CT scan of the sinuses showed a right-sided septal spur and confirmed the absence of the vomer bone. This case was reported at King Abdulaziz Medical City, Riyadh, Saudi Arabia.

Cardiac tumour necrosis factor receptor-associated factor 7 mediates the ubiquitination of apoptosis signal-regulating kinase 1 and aggravates cardiac hypertrophy.

AIMS: Cardiac remodelling is a common pathophysiological process in the development of various cardiovascular diseases, but there is still a lack of effective interventions. Tumour necrosis receptor-associated factor 7 (TRAF7) belongs to the tumour necrosis factor receptor-associated factor family and plays an important role in biological processes. Previous studies have shown that TRAF7 mutations lead to congenital defects and malformations of the heart. However, the molecular mechanisms of TRAF7 in the underlying pathogenesis of pathological cardiac hypertrophy remain unknown. We aim to study the molecular mechanisms and effects of TRAF7 in cardiac remodelling and whether it has the potential to become a therapeutic target for cardiac remodelling. METHODS AND RESULTS: The pressure overload-induced cardiac hypertrophy model in mice was established via transverse aortic constriction (TAC) surgery, and cardiomyocytes were treated with phenylephrine (PE) to induce hypertrophic phenotype. Levels of cardiac dysfunction and remodelling were measured with echocardiography and tissue or cell staining. RNA sequencing, western blot, qRT-PCR, co-immunoprecipitation, and in vivo ubiquitination assays were used to explore the molecular mechanisms. The results showed that the expression of TRAF7 increased gradually during the development of hypertrophy. Accordingly, TRAF7 significantly exacerbated the PE-induced enlargement of primary neonatal Sprague-Dawley rat cardiomyocytes, whereas TRAF7 knockdown alleviated the hypertrophic phenotype in primary cardiomyocytes. Cardiac-specific overexpression of TRAF7 accelerated hypertrophic phenotype in mice and cardiac-specific Traf7 conditional knockout mice improved hypertrophic phenotype induced by TAC. Mechanistically, TRAF7 directly interacted with apoptosis signal-regulating kinase-1 (ASK1) and promoted ASK1 phosphorylation by mediating the K63-linked ubiquitination of ASK1 in response to PE stimulation, which then promoted ASK1 activation and downstream signalling during cardiac hypertrophy. Notably, the pro-hypertrophic effect of TRAF7 was largely blocked by GS4997 in vitro and cardiac-specific Ask1 conditional knockout in vivo. CONCLUSION: In summary, we identified TRAF7 as an essential regulator during cardiac hypertrophy, and modulation of the regulatory axis between TRAF7 and ASK1 could be a novel therapeutic strategy to prevent this pathological process.

CEAM is a mitochondrial-localized, amyloid-like motif-containing microprotein expressed in human cardiomyocytes.

Microproteins synthesized through non-canonical translation pathways are frequently found within mitochondria. However, the functional significance of these mitochondria-localized microproteins in energy-intensive organs such as the heart remains largely unexplored. In this study, we demonstrate that the long non-coding RNA CD63-AS1 encodes a mitochondrial microprotein. Notably, in ribosome profiling data of human hearts, there is a positive correlation between the expression of CD63-AS1 and genes associated with cardiomyopathy. We have termed this microprotein CEAM (CD63-AS1 encoded amyloid-like motif containing microprotein), reflecting its sequence characteristics. Our biochemical assays show that CEAM forms protease-resistant aggregates within mitochondria, whereas deletion of the amyloid-like motif transforms CEAM into a soluble cytosolic protein. Overexpression of CEAM triggers mitochondrial stress responses and adversely affect mitochondrial bioenergetics in cultured cardiomyocytes. In turn, the expression of CEAM is reciprocally inhibited by the activation of mitochondrial stresses induced by oligomycin. When expressed in mouse hearts via adeno-associated virus, CEAM impairs cardiac function. However, under conditions of pressure overload-induced cardiac hypertrophy, CEAM expression appears to offer a protective benefit and mitigates the expression of genes associated with cardiac remodeling, presumably through a mechanism that suppresses stress-induced translation reprogramming. Collectively, our study uncovers a hitherto unexplored amyloid-like microprotein expressed in the human cardiomyocytes, offering novel insights into myocardial hypertrophy pathophysiology.

Clinical features and postoperative outcomes in elderly patients undergoing septal myectomy for hypertrophic cardiomyopathy.

BACKGROUND: Surgical septal reduction is sometimes avoided in older adults due to anticipated high operative risk. OBJECTIVE: To compare the clinical and echocardiographic characteristics of young and older patients undergoing septal myectomy for oHCM and assess differences in early and late postoperative outcomes. METHODS: 2663 patients with oHCM underwent transaortic septal myectomy between 2000 and 2021 and were categorized by age: 18-64, 65-74, and ≥75 years. RESULTS: Median age at the time of surgery increased over the study interval. Female sex (p<0.001), hypertension p<0.001), and diabetes (p=0.004) were more prevalent in older patients, but extent of functional limitation (NYHA) was similar (p=0.092). Elderly patients had thinner septal and posterior walls (p<0.001, p=0.006) and less prominent asymmetry (p<0.001). They are less likely to have positive genetic testing. Hospital mortality was 0.2%, 0.5%, and 1.3% in patients <65, 65-74, and ≥75 (p=0.06), and five-year survival rates were 97%, 93%, and 91%. Septal-to-posterior wall thickness ratio significantly correlated with increased mortality in patients >65, but not in patients <65 (p=0.92). Most of the patients reported improved quality of life following myectomy. CONCLUSION: Clinical characteristics of oHCM in older patients differ from those in younger ones. More symmetric but less extensive ventricular hypertrophy and less positive genetic testing suggests that HCM has distinct clinical and morphological variants in the elderly. Septal myectomy is safe in older patients, but the presence of LV wall asymmetry portends a poorer prognosis.

Regression of postprandial cardiac hypertrophy in burmese pythons is mediated by FoxO1.

As ambush-hunting predators that consume large prey after long intervals of fasting, Burmese pythons evolved with unique adaptations for modulating organ structure and function. Among these is cardiac hypertrophy that develops within three days following a meal (Andersen et al., 2005, Secor, 2008), which we previously showed was initiated by circulating growth factors (Riquelme et al., 2011). Postprandial cardiac hypertrophy in pythons also rapidly regresses with subsequent fasting (Secor, 2008); however, the molecular mechanisms that regulate the dynamic cardiac remodeling in pythons during digestion are largely unknown. In this study, we employed a multiomics approach coupled with targeted molecular analyses to examine remodeling of the python ventricular transcriptome and proteome throughout digestion. We found that forkhead box protein O1 (FoxO1) signaling was suppressed prior to hypertrophy development and then activated during regression, which coincided with decreased and then increased expression, respectively, of FoxO1 transcriptional targets involved in proteolysis. To define the molecular mechanistic role of FoxO1 in hypertrophy regression, we used cultured mammalian cardiomyocytes treated with postfed python plasma. Hypertrophy regression both in pythons and in vitro coincided with activation of FoxO1-dependent autophagy; however, the introduction of a FoxO1-specific inhibitor prevented both regression of cell size and autophagy activation. Finally, to determine whether FoxO1 activation could induce regression, we generated an adenovirus expressing a constitutively active FoxO1. FoxO1 activation was sufficient to prevent and reverse postfed plasma-induced hypertrophy, which was partially prevented by autophagy inhibition. Our results indicate that modulation of FoxO1 activity contributes to the dynamic ventricular remodeling in postprandial Burmese pythons.

Long noncoding RNA AK144717 exacerbates pathological cardiac hypertrophy through modulating the cellular distribution of HMGB1 and subsequent DNA damage response.

DNA damage induced by oxidative stress during cardiac hypertrophy activates the ataxia telangiectasia mutated (ATM)-mediated DNA damage response (DDR) signaling, in turn aggravating the pathological cardiomyocyte growth. This study aims to identify the functional associations of long noncoding RNA (lncRNAs) with cardiac hypertrophy and DDR. The altered ventricular lncRNAs in the mice between sham and transverse aortic constriction (TAC) group were identified by microarray analysis, and a novel lncRNA AK144717 was found to gradually upregulate during the development of pathological cardiac hypertrophy induced by TAC surgery or angiotensin II (Ang II) stimulation. Silencing AK144717 had a similar anti-hypertrophic effect to that of ATM inhibitor KU55933 and also suppressed the activated ATM-DDR signaling induced by hypertrophic stimuli. The involvement of AK144717 in DDR and cardiac hypertrophy was closely related to its interaction with HMGB1, as silencing HMGB1 abolished the effects of AK144717 knockdown. The binding of AK144717 to HMGB1 prevented the interaction between HMGB1 and SIRT1, contributing to the increased acetylation and then cytosolic translocation of HMGB1. Overall, our study highlights the role of AK144717 in the hypertrophic response by interacting with HMGB1 and regulating DDR, hinting that AK144717 is a promising therapeutic target for pathological cardiac growth.

Parotid Gland Suspension Combined with Rhytidectomy to Recontour the Lower Face and Neck Enlargement Caused by Benign Parotid Hypertrophy.

BACKGROUND: Lower face and neck aging and facial shape changes are usually caused by soft tissue descent. During lower face and neck enlargement, parotid hypertrophy is an important influence factor of morphologic changes in the periauricular regions. Most plastic surgery techniques greatly improve the shape of the lower face and neck, but ignore the manipulation of the parotid gland. We aimed to resolve the lower face and neck enlargement caused by parotid hypertrophy. Thus, we performed parotid gland suspension combined with rhytidectomy to improve the lower face and neck contour. METHODS: This retrospective study recruited 22 patients who underwent parotid gland suspension combined with rhytidectomy from 2012 to 2020. The evaluation of patient outcomes was performed by selecting items from the FACE-Q scale. Surgical procedures involved parotid gland exposure and parotid fascia suspension. RESULTS: Patient-perceived age appraisal indicated a younger appearance with follow-ups for approximately 3-10 year after the surgery (mean ± standard deviation - 5.53 ± 3.67). Patients had a high satisfaction level for facial appearance (67.15 ± 16.84), lower face (74.69 ± 21.22), and contour of the parotid gland areas of the neck (65.76 ± 23.62). The lower face and neck contours were narrowed and tightened. The parotid gland area showed a remarkable improvement after surgery. CONCLUSIONS: Parotid gland suspension combined with rhytidectomy obtained an outstanding improvement. This method can achieve a better lower face and neck contour, especially in patients with benign parotid hypertrophy or lower face and neck enlargement in periauricular regions. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Successful Management of an Emerging Distinct Gingival Lesion With a New Histopathological Identity.

Gingival fibroma is a pathological condition that can manifest in pediatric and adult patients, often presenting diagnostic challenges due to shared histopathological characteristics among various lesions. It has been reported as a novel category with distinct histopathological features with new diagnostic criteria. A 40-year-old Saudi female patient with no significant medical history reported a 4×3 cm pedunculated, non-tender, firm, red gingival growth adjacent to the remaining root of tooth number 27 in the maxillary left side. Radiographic assessment yielded remarkable findings. An excisional biopsy was performed, and histopathology analysis confirmed the lesion to be a gingival fibroma. This case marks the first reported instance of gingival fibroma in Saudi Arabia. The recognition of such distinctive histopathological features contributes to improved diagnostic accuracy and highlights the need for vigilance in identifying emerging pathological entities within the gingival overgrowths. The recognition of gingival fibroma as a unique pathological entity is clinically significant, resolving diagnostic challenges in gingival growth cases. Specific diagnostic criteria enable accurate differentiation from similar lesions. The advancement improves patient care and refines the understanding of gingival overgrowth pathogenesis.

Regression of biventricular hypertrophy in acromegalic cardiomyopathy following management of excessive growth hormone secretion.

Acromegalic cardiomyopathy is a significant cardiovascular complication associated with acromegaly, caused by excessive growth hormone production from a pituitary adenoma. Early diagnosis can be challenging due to its insidious nature. This case underscores the critical significance of timely medical intervention, illustrating favorable outcomes resulting from prompt therapeutic measures.

Age-group-specific associations between adenoid/tonsillar hypertrophy and craniofacial features.

BACKGROUND: Age plays an important role in the association between adenotonsillar hypertrophy and craniofacial morphology. This study aimed to analyse the association of adenoid and tonsillar hypertrophy with craniofacial features in different age groups. METHODS: Lateral cephalograms were obtained from 942 patients aged 6-15 years (433 boys, 509 girls). They were divided into three age groups: 6-9 years (n = 189), 9-12 years (n = 383), and 12-15 years (n = 370). According to the different sites of pharyngeal obstruction, they were classified as control group (CG), adenoid hypertrophy group (AG), tonsillar hypertrophy group (TG) and adenotonsillar hypertrophy group (ATG). Cephalometric measurements were performed on each enrolled participant. Comparisons between groups and correlations between these cephalometric variables and obstruction sites were evaluated. RESULTS: At 6-9 years of age, ATG and TG correlated with increased mandibular height (B = 2.2, p = 0.029; B = 2.6, p = 0.042, respectively). At the age of 9-12 years, AG showed a steep growth direction (B = 1.5, p = 0.002), TG showed a higher probability of Class III skeletal pattern (smaller SNB, ANB and SGn/FH, larger Go-Me) and ATG manifested a higher proportion of Class III skeletal pattern. At 12-15 years of age, there was no significant association between cephalometric measurements and pharyngeal lymphoid tissue enlargement. CONCLUSIONS: Children with isolated adenoid hypertrophy have a vertical growth direction at 9-12 years of age. Isolated adenoid hypertrophy correlated with longer mandibular body, more anterior mandible and horizontal skeletal Class III pattern at 6-12 years. Combination of obstructive adenoids and tonsils manifested similarly to children with isolated tonsil hypertrophy.

Volume changes in the contralateral submandibular gland following unilateral gland excision in oral cancer patients.

BACKGROUND: The effects of unilateral submandibular gland excision on the size of the contralateral gland are not well understood, with no human studies reported to date. This study aims to investigate the impact of unilateral submandibular gland excision on the contralateral gland's size, providing insights into compensatory mechanisms and their clinical implications. METHOD: This retrospective study involved patients with oral cancer who underwent unilateral submandibular gland excision and ipsilateral neck dissection at Gangneung-Wonju National University Dental Hospital between 2008 and 2023. Patients were included if they had preoperative and follow-up 3D radiological images. The contralateral submandibular gland volume was measured using 3D Slicer software on preoperative, post-operative, and follow-up radiographic data. RESULTS: The mean volume change of the contralateral submandibular gland was 1.35 ± 2.06 cm3, with a mean change ratio of 1.18 ± 0.24. These changes were statistically significant (p = 0.006). Other factors such as age, gender, and radiotherapy did not significantly affect the volume change ratio (p > 0.05). CONCLUSION: The contralateral submandibular gland exhibits a statistically significant increase in volume following unilateral gland excision, indicating compensatory hypertrophy. This morphological adaptation should be considered in post-operative care and surgical planning for oral cancer patients to optimize outcomes.

Matairesinol blunts adverse cardiac remodeling and heart failure induced by pressure overload by regulating Prdx1 and PI3K/AKT/FOXO1 signaling.

BACKGROUND: Pathological cardiac remodeling is a critical process leading to heart failure, characterized primarily by inflammation and apoptosis. Matairesinol (Mat), a key chemical component of Podocarpus macrophyllus resin, exhibits a wide range of pharmacological activities, including anti-hydatid, antioxidant, antitumor, and anti-inflammatory effects. PURPOSE: This study aims to investigate whether Matairesinol alleviate cardiac hypertrophy and remodeling caused by pressure overload and to elucidate its mechanism of action. METHODS: An in vitro pressure loading model was established using neonatal rat cardiomyocytes treated with angiotensin Ⅱ, while an in vivo model was created using C57 mice subjected to transverse aortic constriction (TAC). To activate the PI3K/Akt/FoxO1 pathway, Ys-49 was employed. Moreover, small interfering RNA (siRNA) and short hairpin RNA (shRNA) were utilized to silence Prdx1 expression both in vitro and in vivo. Various techniques, including echocardiography, wheat germ agglutinin (WGA) staining, HE staining, PSR staining, and Masson trichrome staining, were used to assess cardiac function, cardiomyocyte cross-sectional area, and fibrosis levels in rats. Apoptosis in myocardial tissue and in vitro was detected by TUNEL assay, while reactive oxygen species (ROS) content in tissues and cells was measured using DHE staining. Furthermore, the affinity of Prdx1 with Mat and PI3K was analyzed using computer-simulated molecular docking. Western blotting and RT-PCR were utilized to evaluate Prdx1 levels and proteins related to apoptosis and oxidative stress, as well as the mRNA levels of cardiac hypertrophy and fibrosis-related indicators. RESULTS: Mat significantly alleviated cardiac hypertrophy and fibrosis induced by TAC, preserved cardiac function, and markedly reduced cardiomyocyte apoptosis and oxidative damage. In vitro, mat attenuated ang Ⅱ - induced hypertrophy of nrvms and activation of neonatal rat fibroblasts. Notably, activation of the PI3K/Akt/FoxO1 pathway and downregulation of Prdx1 expression were observed in TAC mice; however, these effects were reversed by Mat treatment. Furthermore, Prdx1 knockdown activated the PI3K/Akt/FoxO1 pathway, leading to exacerbation of the disease. Molecular docking indicated that Molecular docking indicated that Mat upregulated Prdx1 expression by binding to it, thereby inhibiting the PI3K/Akt/FoxO1 pathway and protecting the heart by restoring Prdx1 expression levels. CONCLUSION: Matairesinol alleviates pressure overload-induced cardiac remodeling both in vivo and in vitro by upregulating Prdx1 expression and inhibiting the PI3K/Akt/FoxO1 pathway. This study highlights the therapeutic potential of Matairesinol in the treatment of cardiac hypertrophy and remodeling, providing a promising avenue for future research and clinical application.

Mechanism Actions of Coniferyl Alcohol in Improving Cardiac Dysfunction in Renovascular Hypertension Studied by Experimental Verification and Network Pharmacology.

Renovascular hypertension (RH), a secondary hypertension, can significantly impact heart health, resulting in heart damage and dysfunction, thereby elevating the risk of cardiovascular diseases. Coniferol (CA), which has vascular relaxation properties, is expected to be able to treat hypertension-related diseases. However, its potential effects on cardiac function after RH remain unclear. In this study, in combination with network pharmacology, the antihypertensive and cardioprotective effects of CA in a two-kidney, one-clip (2K1C) mice model and its ability to mitigate angiotensin II (Ang II)-induced hypertrophy in H9C2 cells were investigated. The findings revealed that CA effectively reduced blood pressure, myocardial tissue damage, and inflammation after RH. The possible targets of CA for RH treatment were screened by network pharmacology. The interleukin-17 (IL-17) and tumor necrosis factor (TNF) signaling pathways were identified using a Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The inflammatory response was identified using a Gene Ontology (GO) enrichment analysis. Western blot analysis confirmed that CA reduced the expression of IL-17, matrix metallopeptidase 9 (MMP9), cyclooxygenase 2 (COX2), and TNF α in heart tissues and the H9C2 cells. In summary, CA inhibited cardiac inflammation and fibrohypertrophy following RH. This effect was closely linked to the expression of MMP9/COX2/TNF α/IL-17. This study sheds light on the therapeutic potential of CA for treating RH-induced myocardial hypertrophy and provides insights into its underlying mechanisms, positioning CA as a promising candidate for future drug development.