Introduction Postoperative wound healing is the most important factor in the outcome of any surgical procedure. Wound healing is a dynamic process involving inflammation, neovascularization, granulation, fibroblast proliferation, re-epithelization, and remodeling. It repairs tissue integrity, restoring the body\'s natural defense barrier. A hastened wound healing will help in the quicker re-establishment of the body\'s homeostasis. Carica papaya includes vital nutrients and bioactive substances such as minerals, vitamins, and antioxidants. Its primary active ingredient papain causes the enzymatic debridement of wounds. Hemocoagulase is a thrombin-like serine protease that is mostly employed for its procoagulant and wound-healing characteristics. It is derived from the venom of Bothrops species of snakes. This study aims to compare the wound-healing properties of topical Carica papaya leaf extract and Hemocoagulase after dental extractions. Materials & Methods For 48 patients requiring bilateral therapeutic dental extraction for orthodontic intervention, Carica papaya leaf extract (Caripill 275mg/5ml) was topically applied to the extraction socket on one side, and Hemocoagulase 0.2 CU solution (Botroclot) was applied to the extraction socket on the other side. The bilateral premolars were extracted for orthodontic treatment under local anesthesia. Patients were asked to apply the solution topically twice daily for seven days and were called for review on the seventh day. The assessment of the efficacy of both solutions in post-operative wound healing was the objective of the study. Healing was assessed by using a blinded single observer for all patients using Landry\'s healing index. Results A total of 48 subjects with 96 sites completed the study, with a mean age of 15.4 years. The study population consisted of 24 males and 24 females, which were evenly distributed among the two study groups. On comparison of wound healing index (WHI) scores between the two groups using the Wilcoxon signed rank test, Group A had a significantly higher mean rank than Group B with regards to the wound healing index score, and the results were statistically significant (p = 0.037). Conclusion It can be concluded from the study that Carica papaya leaf extract showed better wound healing in post-extraction sockets compared to Hemocoagulase. This study presents the promising use of natural extracts such as Carica papaya in wound healing because they are easily accessible to patients, more economical, and have no adverse reactions. More studies that focus on natural extracts to promote wound healing are required in the future.

BACKGROUND: Rate control (RC; meanHRHolter ≤ 125 bpm) increases survival in dogs with atrial fibrillation (AF). The mechanisms remain unclear.
OBJECTIVE: Investigate echocardiographic and biomarker differences between RC and non-RC (NRC) dogs. Determine if changes post-anti-arrhythmic drugs (AAD) predict successful RC in subsequent Holter monitoring. Evaluate if early vs late RC affects survival.
METHODS: Fifty-two dogs with AF.
METHODS: Holter-derived mean heart rate, echocardiographic and biomarker variables from dogs receiving AAD were analyzed prospectively at each re-evaluation and grouped into RC or NRC. The primary endpoint was successful RC. Between group comparisons of absolute values, magnitude of change from admission to re-evaluations and end of study were performed using Mann-Whitney tests or unpaired t-tests. Logistic regression explored variables associated with inability to achieve RC at subsequent visits. Kaplan-Meier survival analysis was used to compare survival time of early vs late RC.
RESULTS: At visit 2, 11/52 dogs were RC; at visit 3, 14/52 were RC; and at visit 4, 4/52 were RC. At the end of study, 25/52 remained NRC. At visit 2, both groups had increased cardiac dimensions, but NRC dogs had larger dimensions; biomarkers did not differ. At the end of study, RC showed decreased cardiac dimensions and end-terminal pro-brain natriuretic peptide (NT-proBNP) compared with NRC. No variables were useful at predicting RC success in subsequent visits. Survival analysis found no differences between early vs late RC.
CONCLUSIONS: The RC dogs had decreased cardiac dimensions and NT-proBNP, suggesting HR-mediated reverse-remodeling might benefit survival, even with delayed RC achievement. Pursuit of RC is crucial despite initial failures.

OBJECTIVE: Periodontitis is a chronic infectious disease, characterized by loss of alveolar bone and supporting tissues. Cistanche deserticola(Cd), a local medicinal herb in Xinjiang, possesses favorable biological characteristics and potential applications. Our aim is to investigate the remodeling properties of Cd extract and elucidate the specific mechanisms underlying its therapeutic effects on periodontitis, by employing a combination of basic experimental and network pharmacology approaches.
METHODS: Firstly, UHPLC-QTOF-MS analysis was conducted on Cd extract to identify its main components, with several compounds were identified by standard. Subsequently, in vitro studies were performed using the Cd extract on MC3T3-E1 cells. Cell proliferation viability was assessed using CCK-8 and apoptosis assays, while ALP and ARS staining and quantitative experiments, qRT-PCR, and Western blot assays were employed to evaluate the osteogenic differentiation capability. Network pharmacology analysis was then carried out using the identified compounds to establish a database of Cd components and targets, along with a database of periodontitis. The intersection of these databases revealed the network relationship between Cd components-mapped genes-signaling pathways. KEGG/GO pathway analysis of the targets was performed to filter potential enriched pathways. PPI/CytoHubba protein interaction network analysis was utilized to identify hub genes. Molecular docking and molecular dynamics simulations were employed to analyze the docking and interaction between core gene and Cd components.
RESULTS: We detected 38 major components in the Cd extract, with Echinacoside, Acteoside, Tubuloside A, and Cistanoside A undergoing standard substance verification. In vitro studies indicated that the Cd, at concentrations below 100 μg/ mL, did not affect cell proliferation and inhibited apoptosis. Osteogenesis assays demonstrated that Cd at concentrations of 1 μg/ mL, 10 μg/ mL, and 100 μg/ mL significantly promoted the osteogenic differentiation ability of MC3T3-E1 cells. It also notably upregulated the mRNA and protein levels of Alp, Bmp2, Runx2, and Opn, and the optimal concentration was 10 μg/mL. Network pharmacology results revealed the network relationship between Cd\'s components, crossed targets and signaling pathways. Combined with KEGG/GO pathway analysis and PPI/CytoHubba protein interaction network analysis. The key pathway and hub genes of Cd regulating periodontitis are both related to hypoxia pathway and HIF-1α. Molecular docking results showed a strong binding affinity between Cd compounds and hub genes, and molecular dynamics simulation results indicated the stability of the complexes formed between HIF-1α and several Cd compounds.
CONCLUSIONS: Cistanche deserticola exhibits a notable capacity to promote bone regeneration, and its mechanism of action in regulating periodontitis is associated with the hypoxia signaling pathway. HIF-1α may serve as a potential core gene. Future research will focus on exploring the mechanism of Cd in intervene periodontitis and promoting bone remodeling in hypoxic environment.

Although major pathogenesis mechanisms of heart failure (HF) are well established, the significance of early (mal)adaptive structural changes of cardiomyocytes preceding symptomatic ischemic HF remains ambiguous. The aim of this study is to present the morphological characterization of changes in cardiomyocytes and their reorganization of intermediate filaments during remodeling preceding symptomatic ischemic HF in an adult human heart. A total of 84 myocardial tissue samples from middle-left heart ventricular segments were analyzed histomorphometrically and immunohistochemically, observing the cardiomyocyte\'s size, shape, and desmin expression changes in the remodeling process: Stage A of HF, Stage B of HF, and Stages C/D of HF groups (ACC/AHA classification). Values p < 0.05 were considered significant. The cellular length, diameter, and volume of Stage A of HF increased predominantly by the diameter vs. the control group (p < 0.001) and continued to increase in Stage B of HF in a similar pattern (p < 0.001), increasing even more in the C/D Stages of HF predominantly by length (p < 0.001). Desmin expression was increased in Stage A of HF vs. the control group (p < 0.001), whereas it was similar in Stages A and B of HF (p > 0.05), and most intense in Stages C/D of HF (p < 0.001). Significant morphological changes of cardiomyocytes and their cytoskeletal reorganization were observed during the earliest remodeling events preceding symptomatic ischemic HF.

Introduction: Ventricular remodeling is a mal-adaptive process. Both angiotensin-converting enzyme inhibitors and sacubitril/valsartan have been shown to reverse remodeling in mostly uncontrolled observational studies. There is a lack of head-to-head studies. Methods: This cohort study compares the remodeling effects of angiotensin receptor blockers combined with a neprilysin inhibitor (ARNI) and perindopril in heart failure with reduced ejection fraction (HFrEF) patients between January 2017 and December 2020. Inclusion criteria: (i) age > 18 years, (ii) recent diagnosis of de-novo HFrEF (EF < 40%), (iii) baseline echocardiography performed not more than 2 months prior to treatment onset, and (iv) follow-up echocardiography performed not earlier than 6 months and not later than 18 months posttreatment onset. No prior treatment with renin-angiotensin-aldosterone system inhibitors was permitted in the ARNI group. Left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume (LVEDV), and left ventricular end-systolic volume (LVESV) were analyzed. A two-way repeated measure ANOVA (for normally distributed) and generalized estimating equation test for nonnormally distributed interval dependent variables. Mean comparison between and within groups was performed using the Bonferroni test. Results: Following an average treatment period of 9 months, LVEF improved from 24.9% to 36.4% for ARNI and from 28.7% to 40.5% for perindopril, increments of 11.5% and 11.8% resp. (Bonferroni test [P ≤ .05]). LVEDV was reduced by 8.4 mL and 3.2 mL, and LVESV by 17.9 mL and 10.8 mL for ARNI and perindopril resp. Only the reduction of LVESV for ARNI was statistically significant (P = .007). Conclusion: Both ARNI and perindopril yielded a significant improvement in the LVEF within 9 months. The remodeling effect of ARNI seems stronger because of the greater improvements in left ventricular volumes.

Introduction: Right ventricular remodeling with subsequent functional impairment can occur in some clinical conditions in adults and children. The triggering factors, molecular mechanisms, and, especially, the evolution over time are still not well known. Left ventricular (LV) changes associated with right ventricular (RV) remodeling are also poorly understood. Objectives: The study aimed to evaluate RV morphological, functional, and gene expression parameters in rats submitted to pulmonary artery banding compared to control rats, with the temporal evolution of these parameters, and to analyze the influence of RV remodeling by pulmonary artery banding in rats and their controls over time on LV geometry, histology, gene expression, and functional performance. Methods: Healthy 6-week-old male Wistar-EPM rats weighing 170-200 g were included. One day after the echocardiogram, depending on the animals undergoing the pulmonary artery banding (PAB) procedure or not (control group), they were then randomly divided into subgroups according to the follow-up time: 72 h, or 2, 4, 6, or 8 weeks. In each subgroup, the following were conducted: a new echocardiogram, a hemodynamic study, the collection of material for morphological analysis (hypertrophy and fibrosis), and molecular biology (gene expression). The results were presented as the mean ± standard deviation of the mean. A two-way ANOVA and Tukey post-test compared the variables of the subgroups and evolution follow-up times. The adopted significance level was 5%. Results: There was no significant difference among the subgroups in the percentage of water in both the lungs and the liver (the percentage of water in the lungs ranged from 76% to 78% and that of the liver ranged from 67% to 71%). The weight of the right chambers was significantly higher in PAB animals in all subgroups (RV PAB weighed from 0.34 to 0.48 g, and control subjects, from 0.17 to 0.20 g; right atrium (RA) with PAB from 0.09 to 0.14 g; and control subjects from 0.02 to 0.03 g). In the RV of PAB animals, there was a significant increase in myocyte nuclear volume (97 μm3-183.6 μm3) compared to control subjects (34.2 μm3-57.2 μm3), which was more intense in subgroups with shorter PAB follow-up time, and the fibrosis percentage (5.9%-10.4% vs. 0.96%-1.18%) was higher as the PAB follow-up time was longer. In the echocardiography result, there was a significant increase in myocardial thickness in all PAB groups (0.09-0.11 cm compared to control subjects-0.04-0.05 cm), but there was no variation in RV diastolic diameter. From 2 to 8 weeks of PAB, the S-wave (S\') (0.031 cm/s and 0.040 cm/s), and fractional area change (FAC) (51%-56%), RV systolic function parameters were significantly lower than those of the respective control subjects (0.040 cm/s to 0.050 cm/s and 61%-67%). Furthermore, higher expression of genes related to hypertrophy and extracellular matrix in the initial subgroups and apoptosis genes in the longer follow-up PAB subgroups were observed in RV. On the other hand, LV weight was not different between animals with and without PAB. The nuclear volume of the PAB animals was greater than that of the control subjects (74 μm3-136 μm3; 40.8 μm3-46.9 μm3), and the percentage of fibrosis was significantly higher in the 4- and 8-week PAB groups (1.2% and 2.2%) compared to the control subjects (0.4% and 0.7%). Echocardiography showed that the diastolic diameter and LV myocardial thickness were not different between PAB animals and control subjects. Measurements of isovolumetric relaxation time and E-wave deceleration time at the echocardiography were different between PAB animals and control subjects in all subgroups, but there were no changes in diastolic function in the hemodynamic study. There was also increased expression of genes related to various functions, particularly hypertrophy. Conclusion: 1) Rats submitted to pulmonary artery banding presented RV remodeling compatible with hypertrophy. Such alterations were mediated by increased gene expression and functional alterations, which coincide with the onset of fibrosis. 2) Structural changes of the RV, such as weight, myocardial thickness, myocyte nuclear volume, and degree of fibrosis, were modified according to the time of exposure to pulmonary artery banding and related to variations in gene expression, highlighting the change from an alpha to a beta pattern from early to late follow-up times. 3) The study suggests that the left ventricle developed histological alterations accompanied by gene expression modifications simultaneously with the alterations found in the right ventricle.

The healthy adult aorta exhibits a remarkable homeostatic ability to respond to sustained changes in hemodynamic loads under many circumstances, but this mechanical homeostasis can be compromised or lost in natural aging and diverse pathological processes. Herein, we investigate persistent non-homeostatic changes in the composition and mechanical properties of the thoracic aorta in adult wild-type mice following 14 days of angiotensin II-induced hypertension. We employ a multiscale computational model of arterial growth and remodeling driven by mechanosensitive and angiotensin II-related cell signaling pathways. We find that experimentally observed findings can only be recapitulated computationally if the collagen deposited during the transient period of hypertension has altered properties (deposition stretch, fiber angle, crosslinking) compared with the collagen produced in the original homeostatic state. Some of these changes are predicted to persist for at least six months after blood pressure is restored to normal levels, consistent with the experimental findings.

We analyzed pedicle bone from roe bucks that had died around antler casting or shortly before or during the rutting period. Pedicles obtained around antler casting were highly porous and showed signs of intense osteoclastic activity that had caused the formation of an abscission line. Following the detachment of the antler plus a portion of pedicle bone, osteoclastic activity in the pedicles continued for some time, and new bone was deposited onto the separation plane of the pedicle stump, leading to partial pedicle restoration. Pedicles obtained around the rutting period were compact structures. The newly formed, often very large secondary osteons, which had filled the resorption cavities, exhibited a lower mineral density than the persisting older bone. The middle zones of the lamellar infilling frequently showed hypomineralized lamellae and enlarged osteocyte lacunae. This indicates a deficiency in mineral elements during the formation of these zones that occurred along with peak antler mineralization. We suggest that growing antlers and compacting pedicles compete for mineral elements, with the rapidly growing antlers being the more effective sinks. The competition between the two simultaneously mineralizing structures is probably more severe in Capreolus capreolus than in other cervids. This is because roe bucks regrow their antlers during late autumn and winter, a period of limited food and associated mineral supply. The pedicle is a heavily remodeled bone structure with distinct seasonal variation in porosity. Pedicle remodeling differs in several aspects from the normal bone remodeling process in the mammalian skeleton.

Progression from paroxysmal to persistent atrial fibrillation (AF) is occasionally encountered in patients with previous pacemaker implantation (PMI) for the treatment of tachycardia-bradycardia syndrome (TBS). We aimed to determine the rate of its incidence occurring within the early years after PMI and the predictors. We studied TBS patients who received PMI at 5 core cardiovascular centers. The end point was a conversion from paroxysmal to persistent AF. We extracted 342 TBS patients out of 2579 undergoing PMI. During 5 ± 3.1 years of follow-up, 114 (33.3%) reached the end point. The time to the end point was 2.9 ± 2.7 years. The event rates within a year and 3 years after the PMI were 8.8% and 19.6%, respectively. In the multivariate hazard analyses, hypertension (hazard ratio [HR] 3.2, P = 0.03) and congestive heart failure (HR 2.1, P = 0.04) were found to be independent predictors of the end point occurring within a year after the PMI. Congestive heart failure (HR 1.82, P = 0.04), left atrial diameter of ≥ 40 mm (HR 4.55, P < 0.001), and the use of antiarrhythmic agents (HR 0.58, P = 0.04) were independently associated with the 3-year end point. Prediction models including combinations of those 4 parameters for the 1- and 3-year incidence both exhibited a modest risk discrimination (both c-statistics 0.71). In conclusion, early progression from paroxysmal to persistent AF was less frequent than expected in the TBS patients with PMI. Factors related to atrial remodeling and no use of antiarrhythmic drugs may facilitate the progression.

The benefit of an anterior mitral line (AML) in patients with persistent atrial fibrillation (AF) and anterior atrial scar undergoing ablation has never been investigated.
The purpose of this study was to evaluate the outcomes of AML in addition to standard treatment compared to standard treatment alone (no AML) in this subset of patients.
Patients with persistent AF and anterior low-voltage zone (LVZ) treated with AML in 3 centers were retrospectively enrolled. The patients were matched in 1:1 fashion with patients having persistent AF and anterior LVZ who underwent conventional ablation in the same centers. Matching parameters were age, LVZ burden, and repeated ablation. Primary endpoint was AF/atrial tachycardia (AT) recurrence.
One hundred eight-six patients (age 66 ± 9 years; 34% women) were selected and divided into 2 matched groups. Bidirectional conduction block was achieved in 95% of AML. After median follow-up of 2 years, AF/AT recurrence occurred in 29% of the patients in the AML group vs 48% in the no AML group (log-rank P = .024). On Cox regression multivariate analysis, left atrial volume (hazard ratio [HR] 1.03; P = .006) and AML (HR 0.46; P = .003) were significantly associated with the primary endpoint. On univariate logistic regression, lower body mass index, older age, extensive anterior LVZ, and position of the left atrial activation breakthrough away from the AML were associated with first-pass AML block.
In this retrospective matched analysis of patients with persistent AF and anterior scar, AML in addition to standard treatment was associated with improved AF/AT-free survival compared to standard treatment alone.