The hemostatic and comforting effects of oral adhesive bandages in tooth extraction: a randomized controlled clinical study.

OBJECTIVES: To compare oral adhesive bandages with the classic compression method and evaluate the clinical efficacy of this wound dressing material in improving postoperative comfort, wound healing, and hemostasis in tooth extraction. MATERIALS AND METHODS: The study was designed as a randomized controlled clinical trial. A total of 120 patients were recruited and randomly assigned to the study group and the control group. In the study group, oral adhesive bandages were used as wound dressing. In the control group, patients bit on cotton balls and gauze, as usual. Hemorrhage, comfort, and healing levels were evaluated at postoperative 1 h, 24 h, and 7 days. The adhesion time of the oral adhesive bandages was also recorded. RESULTS: The average adhesion time of the oral adhesive bandages was 26.6 h. At postoperative 1 and 24 h, the hemostatic levels of the oral adhesive bandage group were significantly higher than those of the control group. The oral adhesive bandage group also reported significantly higher comfort scores than the control group. Both groups had similar healing levels and side effects. But the mean score for wound healing was slightly higher in the oral adhesive bandage group. CONCLUSIONS: Oral adhesive bandages were more effective than cotton balls and gauze in providing hemostatic and comfort effects on extraction wounds. CLINICAL RELEVANCE: Oral adhesive bandages possess clinical value in the management of extraction wounds.

Oral cancer cell to endothelial cell communication via exosomal miR-21/RMND5A pathway.

Required for meiotic nuclear division 5 homolog A (RMND5A), a novel ubiquitin E3 Ligase, has been reported to correlate with poor prognosis of several cancers. However, its role in endothelial cells has not been reported. In this study, overexpression of RMND5A in human umbilical vein endothelial cells (HUVECs) was performed via lentiviral infection, followed by MTT, would healing and tube formation assay as well as signaling analysis. Moreover, crosstalk between HUVECs and oral squamous cell carcinoma (OSCC) cells was investigated by indirect co-culture with condition medium or tumor cell derived exosomes. Our results showed that overexpression of RMND5A reduced the proliferation, migration and tube formation ability of HUVECs by inhibiting the activation of ERK and NF-κB pathway. Interestingly, OSCC cells can inhibit RMND5A expression of endothelial cells via exosomal miR-21. In summary, our present study unveils that OSCC cells can activate endothelial cells via exosomal miR-21/RMND5A pathway to promote angiogenesis, which may provide novel therapeutic targets for the treatment of OSCC.

Removal of Ciprofloxacin from Water by a Potassium Carbonate-Activated Sycamore Floc-Based Carbonaceous Adsorbent: Adsorption Behavior and Mechanism.

In this study, a porous carbonaceous adsorbent was prepared from sycamore flocs by pyrolysis method and K2CO3 activation. The effects of preparative conditions of the material on its adsorptive property were explored. The optimal material (SFB2-900) was obtained with a K2CO3/biochar mass ratio of 2:1 at an activation temperature of 900 °C, possessing a huge surface specific area (1651.27 m2/g). The largest adsorption capacity for ciprofloxacin on SFB2-900 was up to 430.25 mg/g. The adsorption behavior was well described by the pseudo-second-order kinetic model and the Langmuir isothermal model. Meanwhile, this process was spontaneous and exothermic. The obtained material showed excellent adsorption performance in the conditions of diverse pH range, ionic strength, and water quality of the solution. The optimum adsorption conditions (pH = 7.01, dosage = 0.6 g/L, and C0 = 52.94 mg/L) determined based on the response surface methodology were in accordance with the practical validation consequences. The good regeneration effect of SFB2-900 manifested that this material had great practical application potential. Combining the experimental results and density functional theory calculation results, the adsorption mechanisms mainly included pore filling, π-π EDA interactions, electrostatic interactions, and H-bonds. The material could be regarded as a novel and high-efficiency adsorbent for antibiotics. Additionally, these findings also provide reference for the reuse of waste biomass in water treatment.

Is it safe and effective to extract impacted maxillary tooth adjacent to maxillary sinus via submaxillary sinus membrane space approach?-a randomized controlled trial.

OBJECTIVE: To evaluate the clinical outcomes following extraction of impacted maxillary tooth adjacent to maxillary via submaxillary sinus membrane space approach. MATERIALS AND METHODS: Seventy-two patients were enrolled in our study. The positions of the maxillary impacted tooth were confirmed by cone-beam computed tomography (CBCT). Cases were randomly divided into two groups: the "submaxillary sinus membrane space approach" was applied in the new method (NM) group, and the conventional "avoid maxillary sinus membrane exposure" strategy was executed in the traditional method (TM) group. The clinical and follow-up data were recorded. RESULTS: The duration of the procedure in the TM group was significantly longer than those in the NM group (P < 0.05). Four teeth were accidentally displaced into the maxillary sinus with MSM perforation. The MSM perforation rate was slightly higher in the TM group than in the NM group, however, without significant difference between the two groups (8/36 vs. 3/36, P = 0.19). The maxillary sinus membrane perforation was associated with the displacement of tooth into the maxillary sinus (OR = 16.2, P = 0.026). The root tip exposure of the adjacent tooth was significantly higher in the TM group than in the NM group (10/36 vs. 1/36, P = 0.006). The incidence of reduced pulp vitality of the adjacent tooth was significantly higher in the TM group (10/36 vs. 1/36, P = 0.006), and it was associated with the exposure of the root tip intraoperatively (OR = 456.5, P < 0.001). The incidence of external root resorption was significantly lower in the NM group, and there was no significant association with the root exposure intraoperatively (OR = 3.7, P = 0.47). CONCLUSIONS: Submaxillary sinus membrane space approach is a safe and efficient approach in extraction of impacted maxillary tooth. It is an alternative way for cases which are in close proximity to the maxillary sinus. CLINICAL RELEVANCE: A novel method to extract impacted maxillary tooth adjacent to maxillary sinus.

M6A Demethylase Inhibits Osteogenesis of Dental Follicle Stem Cells via Regulating miR-7974/FKBP15 Pathway.

N6-methyladenosine (m6A) is the most abundant RNA modification, regulating gene expression in physiological processes. However, its effect on the osteogenic differentiation of dental follicle stem cells (DFSCs) remains unknown. Here, m6A demethylases, the fat mass and obesity-associated protein (FTO), and alkB homolog 5 (ALKBH5) were overexpressed in DFSCs, followed by osteogenesis assay and transcriptome sequencing to explore potential mechanisms. The overexpression of FTO or ALKBH5 inhibited the osteogenesis of DFSCs, evidenced by the fact that RUNX2 independently decreased calcium deposition and by the downregulation of the osteogenic genes OCN and OPN. MiRNA profiling revealed that miR-7974 was the top differentially regulated gene, and the overexpression of m6A demethylases significantly accelerated miR-7974 degradation in DFSCs. The miR-7974 inhibitor decreased the osteogenesis of DFSCs, and its mimic attenuated the inhibitory effects of FTO overexpression. Bioinformatic prediction and RNA sequencing analysis suggested that FK506-binding protein 15 (FKBP15) was the most likely target downstream of miR-7974. The overexpression of FKBP15 significantly inhibited the osteogenesis of DFSCs via the restriction of actin cytoskeleton organization. This study provided a data resource of differentially expressed miRNA and mRNA after the overexpression of m6A demethylases in DFSCs. We unmasked the RUNX2-independent effects of m6A demethylase, miR-7974, and FKBP15 on the osteogenesis of DFSCs. Moreover, the FTO/miR-7974/FKBP15 axis and its effects on actin cytoskeleton organization were identified in DFSCs.

Palatal approach for surgical removal of mesioangularly impacted maxillary third molar - a pilot study.

OBJECTIVE: This study aimed to investigate the application of the palatal approach for surgical removal of IMTM, and to evaluate its success rate, surgical duration, postoperative outcomes, and incidence of complications. METHOD: Patients with mesioangularly IMTM (Archer Classification Class B) in the none-buccal position to the adjacent second molar, which were indicated for surgical removal, were enrolled in this study. The patients were assigned into two groups according to the surgical approach: the buccal or palatal approach. The impacted tooth positions, diagnosis, past dental and medical history, and radiographic examination were recorded pre-operatively. The duration, surgery details, and surgical complications were documented during the surgery. RESULT: 40 teeth were enrolled in our study. All teeth were removed completely. The operation time was significantly shorter in the palatal approach group compared to the buccal approach group (13.3 ± 2.8 min vs. 22.3 ± 5.5 min, P<0.001). The incidence of traumatic ulcers of the lips was significantly higher in the buccal approach group than in the palatal approach group (7/20 vs. 0/20, P = 0.008). CONCLUSION: It is more efficient to perform surgery with a palatal approach if a Class B mesioangularly IMTM is located in the non-buccal aspect of the adjacent second molar. CLINICAL TRIAL REGISTRATION NUMBER: ChiCTR2000040063.

Does the "Root Removal First" strategy prevent postoperative complications in the surgical removal of impacted mandibular third molars in the Pell and Gregory class C and horizontal position? - a randomized clinical trial.

OBJECTIVE: To evaluate the clinical outcomes of the "Root Removal First" strategy in the surgical removal of impacted mandibular third molar (IMTM) in the class C and horizontal position. MATERIALS AND METHODS: A total of 274 cases were finally included in the statistics. The positions of IMTM in the horizontal position were confirmed by cone-beam computed tomography (CBCT). Cases were randomly divided into two groups: the "Root Removal First" strategy was applied in the new method (NM) group, and the conventional "Crown Removal First" strategy was executed in the traditional method (TM) group. The clinical information and relevant data upon follow-up were recorded. RESULTS: The duration of the surgical removal and the incidence rates of lower lip paresthesia in the NM group were significantly lower than those in the TM group. The degree of mobility of the adjacent mandibular second molar (M2) in the NM group was significantly lower than that in the TM group at 30 days and 3 months post-operation. The distal and buccal probing depth of the M2, as well as the exposed root length of M2 in the NM group, were significantly lower than those in the TM group 3 months post-operation. CONCLUSIONS: The "Root Removal First" strategy can reduce the incidence rate of inferior alveolar nerve injury and periodontal complications of the M2 in the surgical removal of IMTM in class C and horizontal position with high efficiency. TRIAL REGISTRATION: ChiCTR2000040063.

Effectiveness evaluation of autotransplanted teeth after performing extraoral endodontic surgery instead of conventional root canal therapy.

PURPOSE: The aim of this study was to examine the viability and efficacy of utilizing extraoral apicoectomy and retrograde filling in combination to seal the root canal system of mature molars without the need for root canal therapy (RCT) during the autotransplantation of teeth (ATT). MATERIALS AND METHODS: This study screened 27 patients who received ATT at the Department of Oral Surgery in the Hospital of Stomatology from 2019 to 2021. Extraoral apicoectomy and retrograde filling were performed, while RCT was temporarily not performed. The study analysed the periodontal status and masticatory function of transplanted teeth one to three years postoperation and used cone-beam computed tomography (CBCT) and periapical radiograph (PA) to evaluate the integrity of the periodontal space and intra/periapical inflammation. The potential predictors of survival/success were analysed statistically. We also conducted questionnaires and chewing efficiency tests. RESULTS: In this study, 27 TTs from 27 patients were found to be fully functional in terms of chewing ability. The overall survival rate was 100% (27/27), and the success rate was 70.4% (19/27). A total of 90.9% (20/22) of patients reported being satisfied or very satisfied with their TTs. Additionally, the chewing efficiency of the transplantation side was on average 82.0% of that of the healthy side, with a significant difference between the two sides (P < 0.05). None of the potential predictors were found to significantly affect the success or survival of the transplanted tooth (TT). CONCLUSION: The combination of extraoral apicoectomy and retrograde filling in TT showed promising outcomes, but further clinical cases and longer follow-up times are still required to validate the treatment plan.

Increased M2 Isoform of Pyruvate Kinase in Fibroblasts Contributes to the Growth, Aggressiveness, and Osteoclastogenesis of Odontogenic Keratocysts.

To investigate the role of glycolysis and the M2 isoform of pyruvate kinase (PKM2) in odontogenic keratocysts (OKCs), the glycolytic flux of primary odontogenic keratocyst fibroblasts (OKC-Fs) and normal oral mucosa fibroblasts (OM-Fs) was determined by glucose uptake, lactate production, and cell proliferation assays. Wound healing assay and Matrigel-coated chamber system were used to investigate the effects of PKM2 on migration and invasion capacities of OKC-Fs. Co-culture of OKC-Fs with osteoclast precursors (RAW264.7 cells) was used to clarify the role of glycolysis in the osteoclastogenic effects of OKC-Fs. In addition, hypoxia-inducible factor 1α and some key enzymes related to glycolysis, including PKM2, 6-phosphofructo-2-kinase/fructose-2, 6-biphosphatase 3, hexokinase 2, and lactate dehydrogenase A, were detected to assess the activation of glycolysis in OKC stroma by immunohistochemistry. Results showed that the glucose uptake and lactate production were significantly higher in OKC-Fs than OM-Fs. PKM2 was elevated in OKC-Fs compared with that in OM-Fs. PKM2 significantly regulated glycolysis, proliferation, migration, invasion, and osteoclastogenic effects of OKC-Fs. Additionally hypoxia-inducible factor 1α, 6-phosphofructo-2-kinase/fructose-2, 6-biphosphatase 3, hexokinase 2, and lactate dehydrogenase A were markedly overexpressed in OKC stroma, and correlated with PKM2. Moreover, the expression of PKM2 was regulated by oxygen concentration in vitro. In sum, PKM2-mediated glycolysis regulated the growth, aggressiveness, and osteoclastogenesis of OKC.

Pyruvate Kinase M2 Mediates Glycolysis in the Lymphatic Endothelial Cells and Promotes the Progression of Lymphatic Malformations.

Metabolism plays a pivotal role in the formation of the lymphatic vasculature. Pyruvate kinase M2 (PKM2) is typically a metabolic marker of proliferating cells and maintains the growth of vascular endothelial cells. In this study, the potential status of PKM2 in lymphatic endothelial cells and the pathogenesis of lymphatic malformations (LMs) was investigated. The glycolysis index, including glucose uptake, ATP, and lactate production, stayed at a relatively high level in human dermal lymphatic endothelial cells (HDLECs) compared with human umbilical vein endothelial cells, whereas the inhibition of PKM2 by shikonin or PKM2 knockdown significantly suppressed glycolysis, migration, tubular formation, and invasion of HDLECs. Moreover, compared with lymphatic vessels in healthy skin, lymphatic vessels of LMs expressed PKM2 highly, and this expression correlated with infection of LMs. Meanwhile, the overexpression of PKM2 in HDLECs strengthened the proliferation, migration, tubular formation, and invasion of HDLECs. The findings from further experiments in a rat LM model support that targeting PKM2 by shikonin significantly impedes the progression of LMs, even in an infected LM rat model. Taken together, these results indicate that PKM2 plays a pivotal role in the activation of LECs and promotes the progression of LMs, whereas the inhibition of PKM2 can effectively suppress the pathogenesis of LM lesions in the rat model.

SR5AL serves as a key regulatory gene in lycopene biosynthesis by Blakeslea trispora.

BACKGROUND: Trisporic acids are considered to be key regulators of carotenoid biosynthesis and sexual reproduction in zygomycetes, but the mechanisms underlying this regulation have not been fully elucidated. RESULTS: In this study, the relationships between trisporic acids and lycopene synthesis were investigated in Blakeslea trispora. The lycopene concentration in single fermentation by the (-) strain with the addition of 24 µg/L trisporic acids was slightly higher than that observed in mated fermentation. After transcriptomic analysis, a steroid 5α-reductase-like gene, known as SR5AL in B. trispora, was first reported. 5α-Reductase inhibitors reduced lycopene biosynthesis and downregulated the expression of sex determination and carotenoid biosynthesis genes. Overexpression of the SR5AL gene upregulated these genes, regardless of whether trisporic acids were added. CONCLUSION: These findings indicated that the SR5AL gene is a key gene associated with the response to trisporic acids.

Industrial aerobic composting and the addition of microbial agents largely reduce the risks of heavy metal and ARG transfer through livestock manure.

Composting is an effective and necessary modality in the recycling of agricultural wastes such as livestock manure, furfural, and straw. However, the risks of heavy metals (HMs) and antibiotic resistance genes (ARGs) during industrial-scale composting process have not been adequately assessed, especially with the addition of bacterial agents. In this study, changes in HMs toxicity, ARGs propagation and microbial community structure during industrial-scale aerobic composting of livestock manure were firstly investigated with various substrates addition. Moreover, the effect of the addition of bacterial agents (Bacillus strains) was evaluated. The results showed that industrial aerobic composting process could immobilize various HMs with different extents and significantly reduce the levels of ARGs such as intl1 and oqxB genes. The addition of Bacillus strains could further reduce the levels of most detected ARGs and the bioavailability of Cu and Cr, and the relative abundance of ereA and tetA was undetectable in some materials. After composting, the main bacterial community structures were similar among different substrates irrespective of bacterial agents and indicated that the composting process was the main driver for their change. This study provides a scientific reference for the safe reuse of livestock manure.

The efficacy of minocycline hydrochloride ointment versus iodoform gauze for alveolar osteitis: A prospective cohort study.

BACKGROUND: Alveolar osteitis (AO) is one of the most commonly encountered complication following tooth extraction, however, to date there is no standard methods of prevention and treatment. The study aims to investigate the efficiency of minocycline hydrochloride ointment (MHO) for the treatment of alveolar osteitis compared with traditional treatment with iodoform gauze (IG). METHODS/DESIGN: STROBE checklist was followed to report this study. All patients underwent tooth extraction either in our department or other hospitals, whom presented with postoperative pain, were screened out to meet the inclusion and exclusion criteria of this study about AO. Patients who fulfilled the inclusion criteria were enrolled in our prospective cohort study, and MHO or IG was administered. The Visual analog scale scores were used to assess the pain score of patients. The healing status of the extraction sockets was followed up. Differences in responses between groups were analyzed using Mann-Whitney U tests. Chi-square test was performed to explore the differences in the teeth position of AO. RESULTS: Of 41,371 patients underwent tooth extraction with post-operative follow-up in our departments, only 20 patients (0.05%) suffered from AO. 31 patients with AO, whose teeth were extracted in other places, were also enrolled. The incidence of AO was significantly higher in third molars than other teeth (P < 0.01). In 28 patients that were treated with MHO, the pain was relieved substantially on day 3 and almost painless on day 7. And only 25% of cases required dressing change more than once. Whilst 23 patients treated with IG, the pain was relieved on day 5, and 56.5% of cases required multiple dressing change. The difference between the two groups of VAS scores had statistical significance during treatment at 8 h, 24 h, 3d, 5d, and 7d. No allergic reaction or further infection occurred. CONCLUSION: MHO has a safer and higher therapeutic effect in the treatment of AO compared with traditional treatment with IG. MHO may become a preferred treatment modality for AO.

Uncontrollable bleeding after tooth extraction from asymptomatic mild hemophilia patients: two case reports.

BACKGROUND: Uncontrollable bleeding after tooth extraction usually occurs in patients with coagulation diseases, including hemophilia, von Willebrand's disease, vitamin K deficiency, platelet deficiency, and taking anticoagulant drugs. Hemophilia A is an X-linked recessive disorder caused by insufficiency of coagulation factor VIII. Mild hemophilia, defined by factor level between 0.05 and 0.40 IU/mL, is characterized by uncontrollable hemorrhage after trauma or invasive operations. Some mild hemophiliacs may remain undiagnosed until late adulthood. Therefore, surgical management of these patients may be relatively neglected. These case reports describe two uncontrollable bleeding patients with unknown mild hemophilia A after tooth extraction. CASE PRESENTATION: This paper reports 2 cases of persistent bleeding after tooth extraction under local anesthesia which could not be completely stopped by routine treatments. Both of them denied prior illness and injury, allergies, anticoagulant medication history, systemic and family illness. The APTT and other coagulation screening tests of the two patients before surgery were normal. Finally, they were diagnosed with mild hemophilia A via coagulation factor assays. The patients acquired complete hemostasis by receiving coagulation factor supplement therapy in hematologic department. CONCLUSION: Mild hemophilia is marked by subclinical, asymptomatic and even normal coagulation test results. The purpose of these case reports is to bring dental professionals' attention that APTT test alone cannot be used to exclude mild hemophilia, and provide reasonable evaluation and treatment procedures of bleeding patients after tooth extraction.

Application effect of computer-aided design combined with three-dimensional printing technology in autologous tooth transplantation: a retrospective cohort study.

BACKGROUND: The activity of donor periodontal membrane is the key factor of autologous tooth healing. The application of digital aided design, 3D printing model and guide plate in autotransplantation of tooth (ATT) is expected to reduce the damage of periodontal membrane and preserve the activity of periodontal membrane, so as to improve the success rate of ATT. This study tried to prove the role of digital technology in improving the success rate of ATT, although there are differences in model accuracy in practice. METHODS: We included 41 tooth autotransplantation cases which assisted by 3D-printed donor models and surgical guides and divided them into two groups in accordance with whether the donor tooth could be placed successfully after the preparation of alveolar socket guided by the model tooth. Then, we compared and analyzed the preparation time of alveolar socket, extra-alveolar time, and number of positioning trials of the donor tooth between the two groups. We also included a comparison of the in vitro time of the donor tooth with that of 15 min. The incidence of complications was included in the prognostic evaluation. RESULTS: The mean preparation time of the alveolar socket, mean extra-alveolar time of donor tooth, and mean number of positioning trials with donor tooth of 41 cases were 12.73 ± 6.18 min, 5.56 ± 3.11 min, and 2.61 ± 1.00, respectively. The group wherein the donor tooth cannot be placed successfully (15.57 ± 6.14 min, 7.29 ± 2.57 min) spent more preparation time of alveolar socket and extra-alveolar time than the group wherein the donor tooth can be placed successfully (9.75 ± 4.73 min, 3.75 ± 2.57 min). The number of positioning trials with the donor tooth of the group wherein the donor tooth cannot be placed successfully (3.19 ± 0.75) was higher than that of the other group (2.00 ± 0.86). There was no significant difference in survival rates between the two groups. CONCLUSIONS: Compared with the traditional tooth autotransplantation, the introduction of computer-aided design combined with 3D printing of the model tooth and surgical guides evidently shortens the preparation time of the alveolar socket and the extra-alveolar time of the donor tooth and reduces the number of positioning trials with the donor tooth regardless of the shape deviation between the model and actual teeth.

Remediation of Pb-Contaminated Soil Using a Novel Magnetic Nanomaterial Immobilization Agent.

The management of heavy metal contaminated soil has received extensive research attention. In this study, a novel immobilization agent (SiO2@Fe3O4@C-COOH) was combined with traditional immobilization agents (TIAs), i.e., CaO, organic matter (OM), and calcium superphosphate (CSP), and used to remediate Pb-contaminated soil. The immobilization effects of Pb in soil was evaluated through pot experiments involving wheat cultivation. The results indicated that SiO2@Fe3O4@C-COOH delivered a higher Pb immobilization efficiency than did TIAs such as CaO, OM, and CSP. The application of SiO2@Fe3O4@C-COOH in combination with TIAs (CaO, OM, and CSP) synergistically enhanced the Pb immobilization efficiency of the soil to 85.10%. Further, joint application in a 54.19% reduction of Pb content in wheat roots, a 65.78% reduction in stems, and a 47.96% in leaves. Thus, the combined application of SiO2@Fe3O4@C-COOH and TIAs significantly reduced the bioavailability of Pb, achieved the purpose of Pb stabilization and soil remediation, and has the potential for wide-spread application in the remediation of Pb-contaminated soils.

Sub-bandgap absorption and photo-response of molybdenum heavily doped black silicon fabricated by a femtosecond laser.

Molybdenum (Mo)-doped black silicon (Si) is obtained by using femtosecond laser irradiation. The concentration of Mo atoms at the depth from 10 to 200 nm has exceeded 1019cm-3. In contrast, the carrier concentration in the Mo-doped layer is lower than 1015cm-3. The surface morphologies with ripple and conical spike microstructures are formed by changing the pulsed laser fluences. The Mo-doped Si samples exhibit a sub-bandgap (1100∼2500nm) absorptance of more than 60% at a wavelength of 1310 nm. A Mo-doped Si photodetector is made, and the responsivity of the device for 1310 nm is up to 76 mA/W at a -10V bias.

The YAP signaling pathway promotes the progression of lymphatic malformations through the activation of lymphatic endothelial cells.

BACKGROUND: To investigate whether the YAP/TAZ (Yes-associated protein/transcriptional coactivator with PDZ binding motif) pathway contributes to the pathogenesis of lymphatic malformations (LMs). METHODS: YAP, TAZ, CTGF (connective tissue growth factor), and Ki-67 were detected in LMs by immunohistochemistry. The colocalization of YAP and Ki-67 was analyzed by double immunofluorescence. Pearson's correlation and cluster analyses were performed to analyze the relationships between these proteins. Human dermal lymphatic endothelial cells (HDLECs) were used for mechanistic investigation. Rat models of LMs were established to investigate the role of the YAP pathway in LM development. RESULTS: Compared with those in normal skin, the expression levels of YAP, TAZ, CTGF, and Ki-67 were significantly upregulated in lymphatic endothelial cells (LECs) of LMs. Interestingly, YAP and CTGF presented much higher expression levels in infected LMs. In experiments in vitro, lipopolysaccharide (LPS) enhanced the expression of YAP in a concentration- and time-dependent manner via the increased phosphorylation of Erk1/2 (extracellular signal-regulated kinase 1/2). Moreover, the proliferation, invasion, and tubule formation of HDLECs increased significantly in accordance with the activation of the YAP signaling pathway. Furthermore, LM rat models validated that LPS facilitated the development of LMs, which was dependent on the activation of YAP. CONCLUSIONS: The data reveal that activation of the YAP signaling pathway in LECs may play a crucial role in the progression of LMs. IMPACT: Compared with that in normal skin, the YAP signaling pathway was activated in LECs of LMs. Inhibiting the YAP signaling pathway attenuated the proliferation, invasion, and tubule formation of HDLECs. Additionally, the activation of the YAP signaling pathway could promote LM development in a rat model. Activation of the YAP signaling pathway in LECs may play a crucial role in the progression of LMs. The YAP signaling pathway was activated in LMs. Inhibition of the YAP signaling pathway could promote regression of the lesions.

Effect of ABCA1 promoter methylation on premature coronary artery disease and its relationship with inflammation.

BACKGROUND: ATP-binding cassette transporter A1 (ABCA1) plays a major role in high-density lipoprotein (HDL) metabolism and reverse cholesterol transport (RCT) and exerts anti-inflammatory effects. Increased ABCA1 promoter methylation level may result in the progression of coronary artery disease. Thus, the present study investigated the association between promoter methylation status of ABCA1 and inflammation in the development of premature coronary artery disease (pCAD). METHODS: PCAD patients and healthy individuals (n = 90 each) were recruited from the Characteristic Medical Center of the Chinese People's Armed Police Force from June to December 2019. Using pyrosequencing, the levels of ABCA1 promoter methylation in their blood samples were evaluated. Serum concentrations of lipids, interleukin 1ß (IL-1ß), C-reactive protein (CRP), and circulating free DNA/Neutrophil extracellular traps (cfDNA/NETs) were also routinely measured and compared between the two groups. P values < 0.05 were considered statistically significant. RESULTS: The mean ABCA1 promoter methylation levels were significantly higher in the pCAD group than in the control group (44.24% ± 3.66 vs. 36.05% ± 2.99, P < 0.001). Based on binary logistic regression analysis, ABCA1 promoter methylation level was identified as an independent risk factor for pCAD development (odds ratio = 2.878, 95% confidence interval: 1.802-4.594, P < 0.001). Furthermore, ABCA1 promoter methylation levels were negatively correlated with HDL levels (r = - 0.488, P < 0.001) and positively correlated with the levels of CRP, cfDNA/NETs, and IL-1ß (r = 0.389, 0.404, 0.385, respectively; P < 0.001). Multiple regression analysis showed that the serum levels of CRP, IL-1ß, and cfDNA/NETs independently affect ABCA1 promoter methylation. CONCLUSIONS: Our findings indicate that high methylation levels at the ABCA1 promoter are associated with low HDL cholesterol levels and an increased risk of pCAD. Inflammatory factors and NETs may be involved in the progression of pCAD by affecting ABCA1 promoter methylation levels.

Pseudolaric Acid B Attenuates High Salt Intake-Induced Hypertensive Left Ventricular Remodeling by Modulating Monocyte/Macrophage Phenotypes.

BACKGROUND Studies in ApoE knockout mice have shown that pseudolaric acid B (PB) can act as an immunomodulatory drug and attenuate atherosclerosis progression by modulating monocyte/macrophage phenotypes. Our previous study demonstrated that high salt intake could shift the phenotype of monocytes/macrophages to an inflammatory phenotype, and that this shift was related to hypertension and hypertensive left ventricular (LV) remodeling. However, no comprehensive assessment of the effects of PB on hypertensive LV remodeling has been conducted. MATERIAL AND METHODS In this study, RAW264.7 macrophages cultured with different concentrations of NaCl were used to investigate the modulating effects of PB on macrophage phenotype. Furthermore, N-nitro-L-arginine methyl ester hypertensive mice were used to investigate the modulating effects of PB on monocyte phenotype. LV remodeling was investigated by echocardiography. LV morphologic staining (for cardiomyocyte hypertrophy and collagen deposition) was performed at the time of sacrifice. RESULTS The results showed that PB significantly improved the viability of RAW264.7 cells, suppressed their phagocytic and migration abilities, and inhibited their phenotypic shift to M1 macrophages. In addition, the blood pressure of PB-treated mice was significantly decreased relative to that of control mice. Furthermore, after PB treatment, the percentage of Ly6Chi monocytes was significantly decreased while that of Ly6Clo monocytes was apparently increased. Moreover, PB preserved LV function and alleviated myocardial fibrosis and cardiomyocyte hypertrophy as measured at the end of the experimental period. The transfer of monocytes from PB-treated mice to hypertensive mice achieved the same effects. CONCLUSIONS Together, these findings indicate that PB exerts its protective effects on hypertensive LV remodeling by modulating monocyte/macrophage phenotypes and warrants further investigation.