Restrictive annuloplasty or replacement on reverse remodeling for nonischemic dilated cardiomyopathy.

BACKGROUND: For patients with nonischemic dilated cardiomyopathy (NIDCM), the indications for and results of mitral surgery remain controversial. We reviewed a strategy of mitral repair and replacement for clinically relevant secondary mitral regurgitation (MR) in patients with NIDCM. METHODS: We retrospectively reviewed 65 patients with advanced NIDCM (LVEF < 40%) who underwent mitral surgery. Of them, 47 (72%) underwent mitral annuloplasty and 18 (28%) replacement for secondary MR. The primary endpoint was postoperative reduction in indexed LV end-systolic volume (LVESVI). RESULTS: At baseline, there was no intergroup difference in LVESVI (123 ± 47 vs. 147 ± 37 ml/m2, P = 0.055), LVEF (27 ± 8% vs. 25 ± 6%, P = 0.41), incidence of severe MR (57% (27/47) vs. 72% (13/18), P = 0.40), or EuroSCORE II score (6.2% vs. 7.6%, P = 0.90). At 6 months, the annuloplasty group reduced LVESVI to a greater degree than the replacement group (P < 0.001), yielding significantly smaller postoperative LVESVI (96 ± 59 vs. 154 ± 61 ml/m2, P < 0.001) and better LVEF (P < 0.001). The rates of moderate/severe recurrent MR were 17% (8/47) and 0%, respectively. Multivariable analysis demonstrated that mitral annuloplasty (OR 6.10, 95% CI 1.14-32.8, P = 0.035) was significantly associated with postoperative LV reverse remodeling. Cumulative survival was not different between the groups (P = 0.26). CONCLUSIONS: In patients with NIDCM, mitral annuloplasty reduced LV volume to a greater degree than did mitral replacement. These findings may assist with surgical options for secondary MR associated with NIDCM.

Identification of the role of DAB2 and CXCL8 in uterine spiral artery remodeling in early-onset preeclampsia.

Aberrant remodeling of uterine spiral arteries (SPA) is strongly associated with the pathogenesis of early-onset preeclampsia (EOPE). However, the complexities of SPA transformation remain inadequately understood. We conducted a single-cell RNA sequencing analysis of whole placental tissues derived from patients with EOPE and their corresponding controls, identified DAB2 as a key gene of interest and explored the mechanism underlying the communication between Extravillous trophoblast cells (EVTs) and decidual vascular smooth muscle cells (dVSMC) through cell models and a placenta-decidua coculture (PDC) model in vitro. DAB2 enhanced the motility and viability of HTR-8/SVneo cells. After exposure to conditioned medium (CM) from HTR-8/SVneoshNC cells, hVSMCs exhibited a rounded morphology, indicative of dedifferentiation, while CM-HTR-8/SVneoshDAB2 cells displayed a spindle-like morphology. Furthermore, the PDC model demonstrated that CM-HTR-8/SVneoshDAB2 was less conducive to vascular remodeling. Further in-depth mechanistic investigations revealed that C-X-C motif chemokine ligand 8 (CXCL8, also known as IL8) is a pivotal regulator governing the dedifferentiation of dVSMC. DAB2 expression in EVTs is critical for orchestrating the phenotypic transition and motility of dVSMC. These processes may be intricately linked to the CXCL8/PI3K/AKT pathway, underscoring its central role in intricate SPA remodeling.

Dopamine promotes osteogenic differentiation of PDLSCs by activating DRD1 and DRD2 during orthodontic tooth movement via ERK1/2 signaling pathway.

Introduction: Orthodontic tooth movement (OTM) involves complex interactions between mechanical forces and periodontal tissue adaptation, mainly mediated by periodontal ligament cells, including periodontal ligament stem cells (PDLSCs), osteoblasts, and osteoclasts. Dopamine (DA), a neurotransmitter known for its critical role in bone metabolism, is investigated in this study for its potential to enhance osteogenic differentiation in PDLSCs, which are pivotal in OTM. This study examined the potential of DA to facilitate OTM by binding to DA receptors (D1R and D2R) and activating the ERK1/2 signaling pathway. We propose that DA's interaction with these receptors on PDLSCs could enhance osteogenic differentiation, thereby accelerating bone remodeling and reducing the duration of orthodontic treatments, which offering a novel approach to improve clinical outcomes in orthodontic care. Methods: This study utilized a rat OTM model, micro-CT, histological analyses, and in vitro assays to investigate dopamine's effect on osteogenesis. PDLSCs were cultured and treated with DA, and cytotoxicity, osteogenic differentiation, gene and protein expression assessed. Results: Dopamine administration significantly increased trabecular bone density and osteogenic marker expression in an OTM rat model. In vitro, DA at 10 nM optimally promoted human PDLSCs osteogenesis without affecting proliferation. Blocking DA receptors or inhibiting the ERK1/2 pathway attenuated these effects, underscoring the importance of dopaminergic signaling in tension-induced osteogenesis during OTM. Conclusion: Taken together, our study reveals that local dopamine administration at a concentration of 10 nM not only enhances tension-induced osteogenesis in vivo but also significantly promotes osteogenic differentiation of PDLSCs in vitro through D1 and D2 receptor-mediated ERK1/2 signaling pathway activation.

Effects of right ventricular remodeling in chronic thromboembolic pulmonary hypertension on the outcomes of balloon pulmonary angioplasty: a 2D-speckle tracking echocardiography study.

BACKGROUND: Balloon pulmonary angioplasty (BPA) improves the prognosis of chronic thromboembolic pulmonary hypertension (CTEPH). Right ventricle (RV) is an important predictor of prognosis in CTEPH patients. 2D-speckle tracking echocardiography (2D-STE) can evaluate RV function. This study aimed to evaluate the effectiveness of BPA in CTEPH patients and to assess the value of 2D-STE in predicting outcomes of BPA. METHODS: A total of 76 patients with CTEPH underwent 354 BPA sessions from January 2017 to October 2022. Responders were defined as those with mean pulmonary artery pressure (mPAP) ≤ 30 mmHg or those showing ≥ 30% decrease in pulmonary vascular resistance (PVR) after the last BPA session, compared to baseline. Logistic regression analysis was performed to identify predictors of BPA efficacy. RESULTS: BPA resulted in a significant decrease in mPAP (from 50.8 ± 10.4 mmHg to 35.5 ± 11.9 mmHg, p < 0.001), PVR (from 888.7 ± 363.5 dyn·s·cm-5 to 545.5 ± 383.8 dyn·s·cm-5, p < 0.001), and eccentricity index (from 1.3 to 1.1, p < 0.001), and a significant increase in RV free wall longitudinal strain (RVFWLS: from 15.7% to 21.0%, p < 0.001). Significant improvement was also observed in the 6-min walking distance (from 385.5 m to 454.5 m, p < 0.001). After adjusting for confounders, multivariate analysis showed that RVFWLS was the only independent predictor of BPA efficacy. The optimal RVFWLS cutoff value for predicting BPA responders was 12%. CONCLUSIONS: BPA was found to reduce pulmonary artery pressure, reverse RV remodeling, and improve exercise capacity. RVFWLS obtained by 2D-STE was an independent predictor of BPA outcomes. Our study may provide a meaningful reference for interventional therapy of CTEPH.

Unveiling the Role of Pregnancy-Associated Plasma Protein A (PAPP-A) in Pregnancy-Associated Breast Cancer: A Comprehensive Review.

Pregnancy-associated breast cancer (PABC) presents unique challenges due to its occurrence during or shortly after pregnancy. Pregnancy-associated plasma protein A (PAPP-A) has emerged as a potential biomarker and regulator in PABC. This comprehensive review examines the role of PAPP-A in PABC, highlighting its involvement in tissue remodeling and cancer progression. Molecular mechanisms linking PAPP-A to breast cancer, including signaling pathways and interactions with other molecules, are explored. The review also discusses the diagnostic and therapeutic implications of PAPP-A dysregulation in PABC, emphasizing the need for further research to elucidate underlying mechanisms and develop targeted therapies. Collaborative efforts among researchers, clinicians, and industry stakeholders are essential for translating findings into clinically relevant interventions to improve outcomes for PABC patients.

Left atrial remodeling and voltage-guided ablation outcome in obese patients with persistent atrial fibrillation.

Background: Obesity is a risk factor for atrial fibrillation (AF). Data regarding left atrial (LA) remodeling in obese patients are scarce. Whether obesity favors AF recurrence after catheter ablation (CA) is still controversial. We assessed the distribution of epicardial atrial fat on computed tomography (CT), LA bipolar voltage, low-voltage zone (LVZ) extent, and the outcome of voltage-guided ablation of persistent AF in obese and non-obese patients. Methods: A total of 139 patients with persistent AF undergoing a first voltage-guided ablation were enrolled and divided into two groups: 74 were non-obese and 65 were obese. Epicardial adipose tissue (EAT) was assessed on a CT scanner. LA endocardial voltage maps were obtained using a 3D mapping system in sinus rhythm. LVZ was defined as a bipolar peak-to-peak voltage amplitude <0.5 mV. Results: LA volume, voltage, and EAT amount were similar in the two groups. LVZ was less frequent in obese patients [12 (18.8%) vs. 26 (35.1%), p = 0.05], particularly on the anterior wall. The posterior and lateral EATs were correlated with posterior and lateral LVZ extent, respectively, in obese patients. After 36 months of follow-up, the AF-free survival rate was similar. Lateral EAT [odds ratio (OR) 1.21, 95% confidence interval (CI) 1-1.4, p = 0.04] and P-wave duration (OR 1.03, 95% CI 1-1.05, p = 0.03), but not body mass index (BMI), were predictors of AF recurrence after CA. Conclusion: In obese patients, LVZ was less marked than in non-obese patients with similar LA volumes, voltage, and EAT amounts. In obese patients, posterior and lateral EATs were correlated with posterior and lateral LVZ extents. Obese patients had a similar and favorable 36-month outcome after AF ablation. BMI was not predictive of AF recurrence.

The role of SWI/SNF complexes in digestive system neoplasms.

Chromatin remodeling is a critical step in the DNA damage response, and the ATP-dependent chromatin remodelers are a group of epigenetic regulators that alter nucleosome assembly and regulate transcription factor accessibility to DNA, preventing genomic instability and tumorigenesis caused by DNA damage. The SWI/SNF chromatin remodeling complex is one of them, and mutations in the gene encoding the SWI/SNF subunit are frequently found in digestive tumors. We review the most recent literature on the role of SWI/SNF complexes in digestive tumorigenesis, with different SWI/SNF subunits playing different roles. They regulate the biological behavior of tumor cells, participate in multiple signaling pathways, interact with multiple genes, and have some correlation with the prognosis of patients. Their carcinogenic properties may help discover new therapeutic targets. Understanding the mutations and defects of SWI/SNF complexes, as well as the underlying functional mechanisms, may lead to new strategies for treating the digestive system by targeting relevant genes or modulating the tumor microenvironment.

Resolvin D2 prevents vascular remodeling, hypercontractility and endothelial dysfunction in obese hypertensive mice through modulation of vascular and proinflammatory factors.

During resolution of inflammation, specialized proresolving mediators (SPMs), including resolvins, are produced to restore tissue homeostasis. We hypothesized that there might be a dysregulation of SPMs pathways in pathological vascular remodeling and that resolvin D2 (RvD2) might prevent vascular remodeling and contractile and endothelial dysfunction in a model of obesity and hypertension. In aortic samples of patients with or without abdominal aortic aneurysms (AAA), we evaluated gene expression of enzymes involved in SPMs synthesis (ALOXs), SPMs receptors and pro-inflammatory genes. In an experimental model of aortic dilation induced by high fat diet (HFD, 60%, eighteen weeks) and angiotensin II (AngII) infusion (four weeks), we studied the effect of RvD2 administration in aorta and small mesenteric arteries structure and function and markers of inflammation. In human macrophages we evaluated the effects of AngII and RvD2 in macrophages function and SPMs profile. In patients, we found positive correlations between AAA and obesity, and between AAA and expression of ALOX15, RvD2 receptor GPR18, and pro-inflammatory genes. There was an inverse correlation between the expression of aortic ALOX15 and AAA growth rate. In the mice model, RvD2 partially prevented the HFD plus AngII-induced obesity and adipose tissue inflammation, hypertension, aortic and mesenteric arteries remodeling, hypercontratility and endothelial dysfunction, and the expression of vascular proinflammatory markers and cell apoptosis. In human macrophages, RvD2 prevented AngII-induced impaired efferocytosis and switched SPMs profile. RvD2 might represent a novel protective strategy in preventing vascular damage associated to hypertension and obesity likely through effects in vascular and immune cells.

Left ventricular concentric remodeling in COPD patients: A cross-sectional observational study.

OBJECTIVE: To investigate the association between left ventricular structure and disease severity in COPD patients. METHODS: Twenty-eight COPD patients were stratified according to the disease severity, using the BODE index, into Lower (n=17) and Higher (n=11) groups, composed of patients with lower severity (BODE <5) and higher severity (BODE ≥5), respectively. Left ventricle (LV) was assessed by 2D-echocardiography. BODE index was calculated using body mass index (BMI); forced expiratory volume in the first second (FEV1, %); modified Medical Research Council (mMRC) and distance walked during 6-minute walk test (6MWD). RESULTS: Patients in the Higher group showed lower oxygen arterial saturation (p=0.02), FEV1 (p<0.01) and 6MWD (p=0.02) and higher value of relative posterior wall thickness (RWT) compared to Lower group (p=0.02). There were significant associations between LV end-systolic diameter (LVESD) and BODE index (r=-0.38, p=0.04), LV end-diastolic diameter (LVEDD) and FEV1 (r=0.44, p=0.02), LVEDD and BMI (r=0.45, p=0.02), LVESD and BMI (r=0.54, p=0.003) and interventricular septal thickness and 6MWD (r=-0.39, p=0.04). CONCLUSIONS: More severe COPD patients, BODE score ≥5, may have higher RWT, featuring a possible higher concentric remodeling of LV in this group. Besides that, a greater disease severity may be related to LV chamber size reduction.

Thymic Stromal Lymphopoietin (TSLP) Is Cleaved by Human Mast Cell Tryptase and Chymase.

Thymic stromal lymphopoietin (TSLP), mainly expressed by epithelial cells, plays a central role in asthma. In humans, TSLP exists in two variants: the long form TSLP (lfTSLP) and a shorter TSLP isoform (sfTSLP). Macrophages (HLMs) and mast cells (HLMCs) are in close proximity in the human lung and play key roles in asthma. We evaluated the early proteolytic effects of tryptase and chymase released by HLMCs on TSLP by mass spectrometry. We also investigated whether TSLP and its fragments generated by these enzymes induce angiogenic factor release from HLMs. Mass spectrometry (MS) allowed the identification of TSLP cleavage sites caused by tryptase and chymase. Recombinant human TSLP treated with recombinant tryptase showed the production of 1-97 and 98-132 fragments. Recombinant chymase treatment of TSLP generated two peptides, 1-36 and 37-132. lfTSLP induced the release of VEGF-A, the most potent angiogenic factor, from HLMs. By contrast, the four TSLP fragments generated by tryptase and chymase failed to activate HLMs. Long-term TSLP incubation with furin generated two peptides devoid of activating property on HLMs. These results unveil an intricate interplay between mast cell-derived proteases and TSLP. These findings have potential relevance in understanding novel aspects of asthma pathobiology.

Electrocardiographic predictors of response to sacubitril/valsartan therapy in heart failure with reduced ejection fraction.

BACKGROUND: Sacubitril/valsartan (SV) is currently recommended as a first-line therapy in patients with heart failure and reduced ejection fraction (HFrEF) due to its significant clinical and prognostic benefit; however, not all patients respond to therapy and predictors of clinical response to SV remain under-studied. AIMS: To identify electrocardiographic (ECG) predictors of response to SV therapy in HFrEF patients. METHODS: A retrospective analysis of a hospital heart failure registry was undertaken. Consecutive HFrEF patients (New York Heart Association class II-III) on maximal-dose SV were studied. Response to SV was defined as ≥10% relative improvement in left ventricular ejection fraction (LVEF) at 3-months post-maximal-dose therapy. Pre-therapy ECGs were retrospectively analyzed for axes and standard wave and interval durations. Logistic regression was used to estimate odds ratios and 95% confidence intervals for associations between predictors and therapeutic response. Backward stepwise regression was employed to develop a parsimonious model. RESULTS: P-wave duration (PWD) 100-120 ms, PWD >120 ms, and QTc >460 ms were associated with response to SV on univariate analysis: OR 18.00 (4.45-122.90), 5.00 (1.47-20.42), and 3.10 (1.18-9.22), respectively. The preferred model that included the former two predictors in combination with pre-therapy creatinine, mineralocorticoid receptor antagonist use, and LVEF was highly selective (area under the ROC curve = 0.868). CONCLUSIONS: Prolongation of both PWD and QTc interval on baseline ECG in HFrEF patients is predictive of therapeutic response to maximal-dose SV therapy and may indicate early cardiac remodeling that is highly amenable to reversal.

8-Iso-prostaglandin F2α as a biomarker of T2-low airway inflammation and remodeling in adult asthma.

BACKGROUND: Although 8-iso-prostaglandin F2a has been proposed as a potential biomarker for oxidative stress in airway diseases, its specific role in asthma remains poorly understood. OBJECTIVE: To evaluate the diagnostic potential of 8-iso-prostaglandin F2a in assessing airway inflammation, airway remodeling, airway hyperresponsiveness, and oxidative stress in asthma. METHODS: Blood and urine concentrations of 8-iso-prostaglandin F2a were quantified using liquid chromatography-tandem mass spectrometry in 128 adults with asthma who had maintained anti-asthmatic medications. Their correlations with clinical data, sputum cell counts, lung function parameters, and serum markers of epithelial/neutrophil activity and airway remodeling were then analyzed. RESULTS: The urinary 8-iso-prostaglandin F2a concentrations were significantly higher in patients with non-eosinophilic asthma than in those with eosinophilic asthma (P < .05). The area under the curve was 0.678, indicating moderate diagnostic accuracy for non-eosinophilic asthma. There were significant correlations with neutrophilic inflammation markers and airway remodeling markers (all P < .05). Negative correlations were observed with forced expiratory volume in 1 s (%), forced expiratory volume in 1 s/forced vital capacity, and forced expiratory flow at 25-75% of forced vital capacity, and serum club cell protein 16 levels (all P < .05). High 8-iso-prostaglandin F2a concentrations were also noted in obese and smoking subgroups (all P < .05). However, the serum 8-iso-prostaglandin F2a concentrations were not correlated with these asthma-related parameters. CONCLUSION: Urinary 8-iso-prostaglandin F2a concentrations are a potential biomarker for phenotyping severe asthma, particularly non-eosinophilic asthma, offering oxidative stress-induced epithelial inflammation/remodeling as an additional target in asthma management.

Evaluating the effect of functionally graded materials on bone remodeling around dental implants.

OBJECTIVES: This study evaluates the potential for osseointegration and remodeling of customized dental implants made from Titanium-Hydroxyapatite Functionally Graded Material (Ti-HAP FGM) with optimized geometry, using the finite element method (FEM). METHODS: The study utilized CT scan images to model and assemble various geometrical designs of dental implants in a mandibular slice. The mechanical properties of Ti-HAP FGMs were computed by varying volume fractions (VF) of hydroxyapatite (0-20%), and a bone remodeling algorithm was used to evaluate the biomechanical characteristics of the ultimate bone configuration in the peri-implant tissue. RESULTS: The findings of the FEA reveal that osseointegration improves with changes in the density and mechanical properties of the bone surrounding Ti-HAP implants, which are influenced by the varying VF of hydroxyapatite in the FGM. SIGNIFICANCE: Increasing the hydroxyapatite fraction improves osseointegration, and appropriate length and diameter selection of Ti-HAP dental implants contribute to their stability and longevity.

Angiotension II directly bind P2X7 receptor to induce myocardial ferroptosis and remodeling by activating human antigen R.

Continuous remodeling of the heart can result in adverse events such as reduced myocardial function and heart failure. Available evidence indicates that ferroptosis is a key process in the emergence of cardiac disease. P2 family purinergic receptor P2X7 receptor (P2X7R) activation plays a crucial role in numerous aspects of cardiovascular disease. The aim of this study was to elucidate any potential interactions between P2X7R and ferroptosis in cardiac remodeling stimulated by angiotensin II (Ang II), and P2X7R knockout mice were utilized to explore the role of P2X7R and elucidate its underlying mechanism through molecular biological methods. Ferroptosis is involved in cardiac remodeling, and P2X7R deficiency significantly alleviates cardiac dysfunction, remodeling, and ferroptosis induced by Ang II. Mechanistically, Ang II interacts with P2X7R directly, and LYS-66 and MET-212 in the in the ATP binding pocket form a binding complex with Ang II. P2X7R blockade influences HuR-targeted GPX4 and HO-1 mRNA stability by affecting the shuttling of HuR from the nucleus to the cytoplasm and its expression. These results suggest that focusing on P2X7R could be a possible therapeutic approach for the management of hypertensive heart failure.

Does adjunctive fixation in conjunction with miniplate affect condylar position and morphology after mandibular advancement through bilateral sagittal split ramus osteotomy? A retrospective 3-dimensional CT comparative study.

To minimize condylar positional and morphological changes after mandibular advancement through bilateral sagittal split ramus osteotomy (BSSRO), surgeons add either a bicortical screw or a two-hole plate distal to the conventional single miniplate. Since there have been no previous studies investigating the effect of this combination, our study aimed to evaluate the short- and long-term effects of these adjunctive fixation methods (AFM) on condylar positional and morphological changes after mandibular advancement through BSSRO. This retrospective cohort study included consecutive patients with retruded mandibles who were treated in the Department of Orthognathic and TMJ Surgery at West China Hospital of Stomatology, Sichuan University. The patients were divided into two groups based on the primary predictor variable, which was the addition of AFM - either a single bicortical screw or a two-hole plate in addition to the single miniplate. The primary outcome variable was the condylar positional and morphological changes after mandibular advancement through BSSRO. Three-dimensional facial CT scans were obtained at three different time points (preoperatively - T0, 1 week postoperatively - T1, and 1 year postoperatively - T2) and analyzed using ITK-SNAP, 3D Slicer, and SlicerSALT software. Intergroup comparisons were conducted with an independent t-test, with a p-value of <0.05 considered significant. Correlations between the variables were estimated by Pearson correlation. The study comprised 51 patients (32 females, 19 males; mean age 25.13 ± 4.24 years), involving a total of 81 condyles (21 unilateral and 60 bilateral). There was a significant difference in long-term condylar displacement in favor of AFM along with a single miniplate (p < 0.001). The bicortical screw group recorded less condylar displacement than the two-hole plate group horizontally (0.11 mm vs 0.22 mm) and sagittally (0.03 mm vs 0.17 mm), but more vertically (0.85 mm vs 0.03 mm). Bone formation associated with AFM occurred on all condylar surfaces, compared with only three surfaces in the single miniplate group. The adjunctive method in addition to the single miniplate fixation method showed less condylar displacement and more bone apposition after mandibular advancement through BSSRO. The follow-up duration variable was the only significant determinant for volumetric changes in the condyle.

Endothelial phosphodiesterase 4B inactivation ameliorates endothelial-to-mesenchymal transition and pulmonary hypertension.

Pulmonary hypertension (PH) is a fatal disorder characterized by pulmonary vascular remodeling and obstruction. The phosphodiesterase 4 (PDE4) family hydrolyzes cyclic AMP (cAMP) and is comprised of four subtypes (PDE4A-D). Previous studies have shown the beneficial effects of pan-PDE4 inhibitors in rodent PH; however, this class of drugs is associated with side effects owing to the broad inhibition of all four PDE4 isozymes. Here, we demonstrate that PDE4B is the predominant PDE isozyme in lungs and that it was upregulated in rodent and human PH lung tissues. We also confirmed that PDE4B is mainly expressed in the lung endothelial cells (ECs). Evaluation of PH in Pde4b wild type and knockout mice confirmed that Pde4b is important for the vascular remodeling associated with PH. In vivo EC lineage tracing demonstrated that Pde4b induces PH development by driving endothelial-to-mesenchymal transition (EndMT), and mechanistic studies showed that Pde4b regulates EndMT by antagonizing the cAMP-dependent PKA-CREB-BMPRII axis. Finally, treating PH rats with a PDE4B-specific inhibitor validated that PDE4B inhibition has a significant pharmacological effect in the alleviation of PH. Collectively, our findings indicate a critical role for PDE4B in EndMT and PH, prompting further studies of PDE4B-specific inhibitors as a therapeutic strategy for PH.

Virus-induced host genomic remodeling dysregulates gene expression, triggering tumorigenesis.

Virus-induced genomic remodeling and altered gene expression contribute significantly to cancer development. Some oncogenic viruses such as Human papillomavirus (HPV) specifically trigger certain cancers by integrating into the host's DNA, disrupting gene regulation linked to cell growth and migration. The effect can be through direct integration of viral genomes into the host genome or through indirect modulation of host cell pathways/proteins by viral proteins. Viral proteins also disrupt key cellular processes like apoptosis and DNA repair by interacting with host molecules, affecting signaling pathways. These disruptions lead to mutation accumulation and tumorigenesis. This review focuses on recent studies exploring virus-mediated genomic structure, altered gene expression, and epigenetic modifications in tumorigenesis.

Learn, unlearn, and relearn post-extraction alveolar socket healing: evolving knowledge and practices.

OBJECTIVE: This review was to offer a comprehensive analysis of currently available evidence on post-extraction alveolar socket healing, including i) the histological and molecular events during alveolar socket healing, ii) the dimensional ridge alterations after socket healing and controversies relating to sinus pneumatisation, iii) the patient-specific factors, procedural elements, and site-related variables influencing socket healing, iv) techniques and effectiveness of alveolar ridge preservation (ARP) procedure, and v) the philosophies and cost-effectiveness of ARP in clinical practice. SOURCES AND STUDY SELECTION: To investigate the dimensional profiles of the alveolar ridge following unassisted healing, an overview of systematic reviews was conducted in February 2024 by two independent reviewers. Four electronic databases were searched in Pubmed, Embase, Web of science and Cochrane Library between 2004-2024 to identify all relevant systematic reviews on post-extraction healing. A further manual search of reviews was also conducted. The articles were further reviewed in full text for relevance. The AMSTAR-2 appraisal tool was adopted to assess methodological quality. Current research pertaining to other listed objectives was objectively analyzed in narration. DATA: 11 out of 459 retrieved studies were selected and ultimately covered in this review on the dimensional changes of alveolar ridge following natural healing: Three systematic reviews and four systematic reviews with meta-analyses. The methodological quality of all included reviews was critically low. CONCLUSION: This review thoroughly examines the healing profiles of post-extraction alveolar sockets and highlights the dynamic process with overlapping phases and the inter-individual variability in outcomes. Alveolar ridge preservation (ARP) procedure is a potential strategy for facilitating prosthetic site development, while the current evidence is limited. Herein, an individualized and prosthetically driven approach is crucial. Further well sized and designed trials with novel biomaterials need to be undertaken, and the role of artificial intelligence in predicting healing and assisting clinical decision-making could be explored. (293 words) CLINICAL SIGNIFICANCE: By advancing our understanding of alveolar socket healing and its management strategies, clinicians can make more informed decisions regarding patient and site level assessment and selection, surgical techniques, and biomaterial choices, ultimately contributing to the enhanced healing process with reduced complications and improved quality of life for patients undergoing tooth extraction and dental implant treatments.

The Role and Potential Mechanisms of Rehabilitation Exercise Improving Cardiac Remodeling.

Rehabilitation exercise is a crucial non-pharmacological intervention for the secondary prevention and treatment of cardiovascular diseases, effectively ameliorating cardiac remodeling in patients. Exercise training can mitigate cardiomyocyte apoptosis, reduce extracellular matrix deposition and fibrosis, promote angiogenesis, and regulate inflammatory response to improve cardiac remodeling. This article presents a comprehensive review of recent research progress, summarizing the pivotal role and underlying mechanism of rehabilitation exercise in improving cardiac remodeling and providing valuable insights for devising effective rehabilitation treatment programs. Graphical Abstract.

Genomic Analysis of Undifferentiated Carcinoma of the Pancreas with Squamous Differentiation: A Case Report.

Pancreatic cancer is an intractable malignancy associated with a dismal prognosis. Undifferentiated carcinoma, a rare subtype, poses a clinical challenge owing to a limited understanding of its molecular characteristics. In this study, we conducted genomic analysis specifically on a case of undifferentiated carcinoma of the pancreas exhibiting squamous differentiation. An 80-year-old male, previously treated for colorectal cancer, presented with a mass with central cystic degeneration in the pancreatic tail. The mass was diagnosed pathologically as undifferentiated carcinoma of the pancreas with squamous differentiation. Despite surgical resection and chemotherapy, the patient faced early postoperative recurrence, emphasizing the aggressive nature of this malignancy. Genomic analysis of distinct histologic components revealed some common mutations between undifferentiated and squamous components, including Kirsten rat sarcoma virus (KRAS) and TP53. Notably, the squamous component harbored some specific mutations in SMARCA4 and SMARCB1 genes that code for members of the SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complex. The common mutations in the undifferentiated and squamous cell carcinoma components from this analysis suggest that they originate from a common origin. The discussion also underscores the scarcity of genomic analyses on undifferentiated carcinoma of the pancreas, with existing literature pointing to SWI/SNF complex-related gene mutations. However, our case introduces chromatin remodeling factor mutations as relevant in squamous differentiation. In conclusion, this study provides valuable insights into the genomic landscape of undifferentiated pancreatic carcinoma with squamous differentiation. These findings suggest the importance of further research and targeted therapies to improve the management of undifferentiated carcinoma of the pancreas and enhance patient outcomes.