Apoptotic Vesicles: Therapeutic Mechanisms and Critical Issues.

Apoptosis is the most prominent mode of programmed cell death and is necessary for the maintenance of tissue homeostasis. During cell apoptosis, a distinctive population of extracellular vesicles is generated, termed apoptotic vesicles (apoVs). ApoVs inherit a variety of biological molecules such as proteins, RNAs, nuclear components, lipids, and gasotransmitters from their parent cells. ApoVs have shown promising therapeutic potential for inflammation, tumors, immune disorders, and tissue regeneration. In addition, apoVs can be used as drug carriers, vaccine development, and disease diagnosis. Recently, apoVs have been used in clinical trials to treat a variety of diseases, such as temporomandibular joint osteoarthritis and the regeneration of functional alveolar bone. Here, we review the history of apoV research, current preclinical and clinical studies, and the potential issues of apoV application.

Ice sheet-free West Antarctica during peak early Oligocene glaciation.

One of Earth's most fundamental climate shifts, the greenhouse-icehouse transition 34 million years ago, initiated Antarctic ice sheet buildup, influencing global climate until today. However, the extent of the ice sheet during the Early Oligocene Glacial Maximum (~33.7 to 33.2 million years ago) that immediately followed this transition-a critical knowledge gap for assessing feedbacks between permanently glaciated areas and early Cenozoic global climate reorganization-is uncertain. In this work, we present shallow-marine drilling data constraining earliest Oligocene environmental conditions on West Antarctica's Pacific margin-a key region for understanding Antarctic ice sheet evolution. These data indicate a cool-temperate environment with mild ocean and air temperatures that prevented West Antarctic Ice Sheet formation. Climate-ice sheet modeling corroborates a highly asymmetric Antarctic ice sheet, thereby revealing its differential regional response to past and future climatic change.

[Euonymus alatus delays progression of diabetic kidney disease in mice by regulating EGFR tyrosine kinase inhibitor resistance signaling pathway].

OBJECTIVE: To explore the therapeutic mechanism of Euonymus alatus for diabetic kidney disease (DKD). METHODS: TCMSP, PubChem and Swiss Target Prediction databases were used to obtain the active ingredients in Euonymus alatus and their targets. GEO database and R language were used to analyze the differentially expressed genes in DKD. The therapeutic targets of DKD were obtained using GeneCards, DisGeNet, OMIM and TTD databases. The protein-protein interaction network and the "drug-component-target-disease" network were constructed for analyzing the topological properties of the core targets, which were functionally annotated using GO and KEGG pathway enrichment analyses. Molecular docking was performed for the core targets and the main pharmacologically active components, and the results were verified in db/db mice. RESULTS: Analysis of GSE96804, GSE30528 and GSE30529 datasets (including 60 DKD patients and 45 normal samples) identified 111 differentially expressed genes in DKD. Network pharmacology analysis obtained 161 intersecting genes between the target genes of Euonymus alatus and DKD, including the key core target genes SRC, EGFR, and AKT1. The core active ingredients of Euonymus alatus were quercetin, kaempferol, diosmetin, and naringenin, which were associated with responses to xenobiotic stimulionus and protein phosphorylation and regulated EGFR tyrosine kinase inhibitor resistance pathways. Molecular docking suggested good binding activities of the core active components of Euonymus alatus with the core targets. In db/db mouse models of DKD, treatment with Euonymus alatus obviously ameliorated kidney pathologies, significantly inhibited renal expressions of SRC, EGFR and AKT1, and delayed the progression of DKD. CONCLUSION: Euonymus alatus contains multiple active ingredients such as quercetin, kakaferol, diosmetin, naringenin, which regulate the expressions of SRC, EGFR, and AKT1 to affect the EGFR tyrosine kinase inhibitor resistance signaling pathway to delay the progression of DKD.

[A two-dimensional photographic and three-dimensional digital dental model comparative analysis in maxillary anterior teeth].

Objective: To assess the accuracy of two-dimensional (2D) photographs in measuring esthetic parameters of the maxillary anterior teeth by comparing them with measurements obtained from three-dimensional (3D) dental models. Methods: A total of one hundred volunteers (49 males, 51 females, aged 18-23 years) were recruited from School and Hospital of Stomatology, Wuhan University from January to February 2024. 3D digital models of their dentitions were obtained using an intraoral scanner, and standardized frontal 2D intraoral photographs were captured with a digital camera. The lengths, widths and width/length ratio of the bilateral incisors, lateral incisors and canines were measured on both the 3D digital models and the 2D intraoral photographs. The width ratios of adjacent maxillary anterior were also calculated on the 2D intraoral photographs and the frontal view of 3D digital models. Results: The widths of lateral incisors [(5.85±0.60) mm] and canines [(4.73±0.71) mm] and the lengths of canines [(8.72±0.96) mm] in the 2D intraoral photographs were significantly lower than those in 3D digital models [(6.65±0.59), (7.76±0.60), (8.90±0.86) mm] (t=-18.24, P<0.001; t=-54.43, P<0.001; t=-4.40, P<0.001), while there were no significant differences in the lengths and widths of the other teeth (P>0.05). The width/length ratios measured from the 2D intraoral photographs for the lateral incisors and canines (0.74±0.08, 0.55±0.08) were significantly lower than those measured in the 3D digital models (0.84±0.09, 0.88±0.09) (t=-19.68, P<0.001; t=-50.21, P<0.001), and the width/length ratio of the central incisors showed no significant difference between the two groups (P>0.05). The width ratios of canines/lateral incisors and lateral incisors/central incisors measured on the 2D intraoral photographs (0.72±0.06, 0.85±0.11) were significantly smaller than those measured in the frontal view of 3D digital models (0.75±0.06, 0.89±0.11) (t=-9.31, P<0.001; t=-6.58, P<0.001). Conclusions: There is a difference between 2D and 3D measurement results of teeth in the esthetic area and the magnitude of the difference varies with their position in the dental arch. When analyzing the measurement of the anterior teeth, it is necessary to choose the appropriate method according to the target tooth position.

[Analysis of non-alcoholic fatty liver disease differences from metabolic dysfunction-associated fatty liver disease based on clinical features].

Objective: To explore the clinical features of fatty liver disease (FLD) from non-alcoholic fatty liver disease (NAFLD) to metabolic dysfunction-associated fatty liver disease (MASLD), so as to elucidate its clinical application value under three renames. Methods: Patients who were hospitalized in the Department of Hepatology, Hospital of Traditional Chinese Medicine Affiliated to Xinjiang Medical University, from January 2020 to September 2023 and met the diagnosis of NAFLD, metabolic-associated fatty liver disease (MAFLD), or MASLD were selected as the research subjects. The clinical indicators differences among the three groups of patients were compared, mainly including general information (age, gender, body mass index, past history, etc.), serological indicators (liver and kidney function, blood lipids, blood sugar, coagulation function, etc.), non-invasive liver fibrosis indicators, fat attenuation parameters, etc. Measurement data were analyzed using ANOVA and the rank sum test, while count data were analyzed using the χ(2) test. Results: NAFLD, MAFLD, and MASLD prevalence rates among 536 cases were 64.0%, 93.7%, and 100%, respectively. 318 cases (59.3%) met the three fatty liver names at the same time among them. Male population proportions in NAFLD, MAFLD, and MASLD were 30.9%, 55.8%, and 53.9%, respectively. The alcohol consumption history proportion was 0, 36.7%, and 36.0%, respectively. The smoking history proportion was 7.0%, 31.9%, and 30.6%, respectively. The body mass index was (27.66 ± 3.97), (28.33 ± 3.63), and (27.90 ± 3.89) kg/m(2), respectively. The γ-glutamyltransferase levels were 26.6 (18.0, 47.0) U/L, 31.0 (20.0, 53.0) U/L, and 30.8 (19.8, 30.8) U/L, respectively. The high-density lipoprotein cholesterol levels were 1.07 (0.90, 1.23) mmol/L, 1.02 (0.86, 1.19) mmol/L, and 1.03 (0.87,1.21) mmol/L, respectively. Sequentially measured uric acid was (322.98 ± 84.51) µmol/L, (346.57 ± 89.49) µmol/L, and (344.89 ±89.67) µmol/L, respectively. Sequentially measured creatinine was 69.6 (62.9, 79.0) µmol/L, 73.0 (65.0, 83.5) µmol/L, and 73.0 (65.0, 83.0) µmol/L, respectively. The sequential analysis of obesity proportion was 74.3%, 81.7%, and 76.5%, respectively, with statistically significant differences (P<0.05). Conclusion: Compared with the NAFLD population, the MAFLD and MASLD populations were predominantly male, obese, and had a history of smoking and drinking. The levels of γ-glutamyltransferase, uric acid, and creatinine were slightly higher, while the levels of high-density lipoprotein cholesterol were lower. MASLD appeared in NAFLD and MAFLD on the basis of inheritance and progression, emphasizing once again the important role of metabolic factors in a fatty liver.

DPSCs regulate epithelial-T cell interactions in oral submucous fibrosis.

BACKGROUND: Oral submucous fibrosis (OSF) is a precancerous lesion characterized by fibrous tissue deposition, the incidence of which correlates positively with the frequency of betel nut chewing. Prolonged betel nut chewing can damage the integrity of the oral mucosal epithelium, leading to chronic inflammation and local immunological derangement. However, currently, the underlying cellular events driving fibrogenesis and dysfunction are incompletely understood, such that OSF has few treatment options with limited therapeutic effectiveness. Dental pulp stem cells (DPSCs) have been recognized for their anti-inflammatory and anti-fibrosis capabilities, making them promising candidates to treat a range of immune, inflammatory, and fibrotic diseases. However, the application of DPSCs in OSF is inconclusive. Therefore, this study aimed to explore the pathogenic mechanism of OSF and, based on this, to explore new treatment options. METHODS: A human cell atlas of oral mucosal tissues was compiled using single-cell RNA sequencing to delve into the underlying mechanisms. Epithelial cells were reclustered to observe the heterogeneity of OSF epithelial cells and their communication with immune cells. The results were validated in vitro, in clinicopathological sections, and in animal models. In vivo, the therapeutic effect and mechanism of DPSCs were characterized by histological staining, immunohistochemical staining, scanning electron microscopy, and atomic force microscopy. RESULTS: A unique epithelial cell population, Epi1.2, with proinflammatory and profibrotic functions, was predominantly found in OSF. Epi1.2 cells also induced the fibrotic process in fibroblasts by interacting with T cells through receptor-ligand crosstalk between macrophage migration inhibitory factor (MIF)-CD74 and C-X-C motif chemokine receptor 4 (CXCR4). Furthermore, we developed OSF animal models and simulated the clinical local injection process in the rat buccal mucosa using DPSCs to assess their therapeutic impact and mechanism. In the OSF rat model, DPSCs demonstrated superior therapeutic effects compared with the positive control (glucocorticoids), including reducing collagen deposition and promoting blood vessel regeneration. DPSCs mediated immune homeostasis primarily by regulating the numbers of KRT19 + MIF + epithelial cells and via epithelial-stromal crosstalk. CONCLUSIONS: Given the current ambiguity surrounding the cause of OSF and the limited treatment options available, our study reveals that epithelial cells and their crosstalk with T cells play an important role in the mechanism of OSF and suggests the therapeutic promise of DPSCs.

High-Performance Dental Resins Containing a Starburst Monomer.

Dimethacrylate-based chemistries feature extensively as resin monomers in dental resin-based materials due to their distinguished overall performance. However, challenges endure, encompassing inadequate mechanical attributes, volumetric shrinkage, and estrogenicity. Herein, we first synthesized a novel resin monomer, 9-armed starburst polyurethane acrylate (NPUA), via the grafting-onto approach. Compared to the primary commercial dental monomer 2,2-bis [p-(2'-hydroxy-3'-methacryloxypropoxy) phenyl] propane (Bis-GMA) (with a viscosity of 1,174 ± 3 Pa·s and volumetric shrinkage of 4.7% ± 0.1%), the NPUA monomer achieves the lower viscosity (158 ± 1 Pa·s), volumetric shrinkage (2.5% ± 0.1%), and cytotoxicity (P < 0.05). The NPUA-based resins exhibit the higher flexural strength, flexural modulus, hardness, and hydrophobicity and lower volumetric shrinkage, water absorption, and solubility compared to the Bis-GMA (70 wt%)/TEGDMA (30 wt%) resins. The NPUA-based composites exhibit significantly higher flexural strength, flexural modulus, and hardness and lower volumetric shrinkage (171.4 ± 3.0 MPa, 12.6 ± 0.5 GPa, 2.0 ± 0.2 GPa, and 3.4% ± 0.2%, respectively) compared to the Bis-GMA group (120.3 ± 4.7 MPa, 9.4 ± 0.7 GPa, 1.5 ± 0.1 GPa, and 4.7% ± 0.2%, respectively; P < 0.05). This work presents a viable avenue for augmenting the physicochemical attributes of dental resins.

[Ultrasound-guided percutaneous thermal ablation assisted by artificial ascites and soft tissue edema in the treatment of special-region hepatic tumors].

Objective: To explore the application value and operation skills of ultrasound-guided percutaneous thermal ablation assisted by artificial ascites or/and soft tissue edema in the treatment of special hepatic tumors located nearby the diaphragm, heart, stomach, gastrointestinal tract, gall bladder, kidney, and other organs. Methods: The clinical data of 132 patients with special-region hepatic tumors treated with ultrasound-guided percutaneous thermal ablation aided by artificial ascites and/or artificial soft tissue edema were retrospectively analyzed. Intraoperative contrast-enhanced ultrasound was used to guide ablation when necessary. During the operation, the ablation needle was lifted or pressed down, or the direction of the needle handle was changed to protect vital organs. The technical success rate of artificial ascites and/or soft tissue edema formation, the complete in activation rate of the tumor, and the complications were observed. Results: There were 74 patients (108 lesions) treated with radiofrequency ablation and 58 patients (82 lesions) treated with microwave ablation. Among them, 81 cases was successfully injected artificial abdominal ascites, with a water volume of (1 301±685) ml; artificial soft tissue edema was successfully formed for 19 patients, with a water volume of (534±258) ml. Both artificial ascites and artificial soft tissue edema were built for 30 patients. The success rate of this hydro-isolation technique was 98.5% (130/132). 129 patients successfully completed the treatment, and the complete inactivation rate of the tumor was 92.5% (172/186). The average postoperative hospital stay was three days. No patient had serious complications, such as surface tumor rupture, gastrointestinal injury, or diaphragm perforation. Conclusions: For hepatic tumors located adjacent to other organs such as the diaphragm, heart, gastrointestinal tract, gallbladder, and kidney, the application of artificial ascites and/or artificial soft tissue edema can reduce the damage to these organs, as well as reduce the possibility of tumor rupture and diaphragm perforation. These methods are safe and effective in ultrasound-guided percutaneous thermal ablation.

CT venography combined with ultrasound-guided minimally invasive treatment for recurrent varicose veins: a pilot paired-design clinical trial.

AIM: To compare 1-year outcomes of computed tomography venography (CTV) combined with ultrasound-guided minimally invasive treatment with ascending phlebography and ultrasound-guided treatment for recurrent varicose veins. MATERIALS AND METHODS: Consecutive patients with unilateral recurrent varicose veins were matched by gender, age, C classification, and degree of obesity, and randomised in a 1:1 ratio to receive either CTV (CTV group) or ascending phlebography (control group) combined with ultrasound-guided minimally invasive treatment. Patients were followed up by clinical and ultrasound examination. Follow-up was scheduled at 1 week, and 3, 6, and 12 months. The primary outcome measure was the Venous Clinical Severity Score (VCSS) at 12 months. Measures of secondary outcome included Chronic Insufficiency Venous International Questionnaire-20 (CIVIQ-20) score, recurrence of varicose vein or ulcer during 12 months, ulcer healing time, detection and location of treated veins. RESULTS: Eighty patients were enrolled. Median VCSS in the CTV group was lower than it in the control group (p=0.04) and the CIVIQ-20 score was higher than the control group (p=0.02). By 12 months, no symptomatically recurrent varicose veins or ulcers had occurred. The ulcer healing time in CTV group was shorter (p<0.01). A greater number of patients had treated veins detected using CTV than by ascending venography (p=0.01), especially among patients with recurrence reflux veins in the groin, perineum, and vulva (p<0.01). CONCLUSION: CTV combined with ultrasound may be more helpful than ascending phlebography combined with ultrasound to improve treatment efficacy for recurrent varices. These results should be verified by an future study with more patients and long-term follow-up.

Clinical and radiographic outcomes of a combined surgery approach to treat peri-implantitis.

Peri-implant infra-bony defects are difficult to treat, and data on the management of peri-implantitis are lacking. The aim of this study was to evaluate the effect of a combined surgical approach to manage peri-implantitis: implantoplasty with xenogeneic bone grafting and a concentrated growth factor membrane. Two independent examiners analysed the medical records and radiographs taken before surgery and at the last follow-up. Data were analysed at the implant level; some patient-level data (age, sex, smoking habit) were also considered. Linear regression analysis with generalized estimating equations (GEE) was used to explore the effect of variables of interest (including marginal bone level (MBL)) on implantitis treatment success and resolution rates. The effect of the prosthesis type on postoperative clinical and radiographic parameters was also explored by GEE, with adjustment for age, sex, tooth site, location, follow-up duration, and implant length (model IV including all). Thirty patients with 72 implants were investigated. The implant survival rate was 100% over a mean observation period of 3.3 years (range 2-11 years). The treatment success rate (bone loss <0.5 mm, no bleeding on probing (BOP), no suppuration, probing depth (PD) < 5 mm) was higher in females than males (50% vs 19.0%; P = 0.008). At the last postoperative follow-up, the MBL (1.51 ± 1.07 vs 4.01 ± 1.13 mm), PD (3.61 ± 0.84 vs 6.54 ± 1.01 mm), and BOP (23.38 ± 23.18% vs 79.17 ± 15.51%) were significantly reduced when compared to pre-surgery values (all P < 0.001). Furthermore, a significantly higher PD reduction (ß = -1.10 mm, 95% confidence interval -1.97 to -0.23 mm, P = 0.014) was observed for implants with a single crown than a full-arch prosthesis (GEE model IV). Preliminary clinical and radiographic data indicate that implantoplasty in combination with surgery could be an effective treatment option for peri-implantitis.