Integrated Network Pharmacology Analysis and Experimental Validation to Elucidate the Mechanism of Acteoside in Treating Diabetic Kidney Disease.

Background: Acteoside, an active ingredient found in various medicinal herbs, is effective in the treatment of diabetic kidney disease (DKD); however, the intrinsic pharmacological mechanism of action of acteoside in the treatment of DKD remains unclear. This study utilizes a combined approach of network pharmacology and experimental validation to investigate the potential molecular mechanism systematically. Methods: First, acteoside potential targets and DKD-associated targets were aggregated from public databases. Subsequently, utilizing protein-protein interaction (PPI) networks, alongside GO and KEGG pathway enrichment analyses, we established target-pathway networks to identify core potential therapeutic targets and pathways. Further, molecular docking facilitated the confirmation of interactions between acteoside and central targets. Finally, the conjectured molecular mechanisms of acteoside against DKD were verified through experimentation on unilateral nephrectomy combined with streptozotocin (STZ) rat model. The underlying downstream mechanisms were further investigated. Results: Network pharmacology identified 129 potential intersected targets of acteoside for DKD treatment, including targets such as AKT1, TNF, Casp3, MMP9, SRC, IGF1, EGFR, HRAS, CASP8, and MAPK8. Enrichment analyses indicated the PI3K-Akt, MAPK, Metabolic, and Relaxin signaling pathways could be involved in this therapeutic context. Molecular docking revealed high-affinity binding of acteoside to PIK3R1, AKT1, and NF-κB1. In vivo studies validated the therapeutic efficacy of acteoside, demonstrating reduced blood glucose levels, improved serum Scr and BUN levels, decreased 24-hour urinary total protein (P<0.05), alongside mitigated podocyte injury (P<0.05) and ameliorated renal pathological lesions. Furthermore, this finding indicates that acteoside inhibits the expression of pyroptosis markers NLRP3, Caspase-1, IL-1ß, and IL-18 through the modulation of the PI3K/AKT/NF-κB pathway. Conclusion: Acteoside demonstrates renoprotective effects in DKD by regulating the PI3K/AKT/NF-κB signaling pathway and alleviating pyroptosis. This study explores the pharmacological mechanism underlying acteoside's efficacy in DKD treatment, providing a foundation for further basic and clinical research.

Effect of varying auxiliaries on maxillary incisor torque control with clear aligners: A finite element analysis.

INTRODUCTION: This study aimed to evaluate the effects of varying auxiliaries on tooth movement and stress distribution when maxillary central incisors were torqued 1° with a clear aligner through finite element analysis. METHODS: Three-dimensional finite element models, including maxillary alveolar bone, periodontal ligament, dentition, and clear aligner, were constructed. According to the auxiliaries designed on the maxillary central incisor, 5 models were created: (1) without auxiliaries (control model), (2) with the power ridge, (3) with the semi-ellipsoid attachment, (4) with the horizontal rectangular attachment, and (5) with the horizontal cylinder attachment. The tooth movement and periodontal ligament stress distribution after a palatal root torque of 1° were analyzed for each of the 5 models. RESULTS: With 1° torque predicted, the maxillary central incisor without auxiliaries showed a tendency of labial tipping, mesial tipping, and intrusion. The rotation center moved occlusally in the power ridge model. The labiolingual inclination variation increased in the semi-ellipsoid attachment model but decreased in the power ridge model. The maxillary central incisor is twisted in the distal direction in the power ridge model. The maxillary central incisor of the horizontal rectangular attachment and the horizontal cylinder attachment model behaved similarly to the control model. Periodontal stresses were concentrated in the cervical and apical areas. The maximum von Mises stresses were 11.6, 12.4, 3.81, 1.14, and 11.0 kPa in the 5 models. The semi-ellipsoid attachment model exhibited a more uniform stress distribution than the other models. CONCLUSIONS: Semi-ellipsoid attachment performed better efficacy on labiolingual inclination, and power ridge performed better efficacy on root control. However, a distal twist of maxillary incisors could be generated by the power ridge.

Efficacy of upper-incisor torque control with clear aligners: a retrospective study using cone-beam computed tomography.

OBJECTIVES: The objectives of this retrospective clinical study were to evaluate the efficacy of clear aligners on upper-incisor torque control, with the expectation of providing guidance for clinics. MATERIALS AND METHODS: Pretreatment (T0) and posttreatment (T1) cone-beam computed tomography (CBCT) scans of 47 patients with a nonextraction treatment using clear aligners were obtained and 120 upper-incisors with torque ≥5° were selected. Voxel-based superimpositions were performed using Dolphin imaging software and achieved movements were then measured. Difference between achieved and predicted movement (DAPM) and the efficiency for upper-incisor torque were used to evaluate the torque control efficacy. RESULTS: The achieved torque movement with clear aligners was lower than predicted significantly, as the mean efficiency was 46.81±33.95%. Additionally, the achieved incisor movement of the crown and root differed significantly from the predicted movement, especially root movement. CONCLUSIONS: Clear aligners struggle to control upper-incisor torque, particularly root movement. In that case, overcorrection is necessary to prevent torque loss. CLINICAL RELEVANCE: Clear aligners remain a limitation on torque control and overcorrection should be considered.

Thiazolidinediones play a positive role in the vascular endothelium and inhibit plaque progression in diabetic patients with coronary atherosclerosis: A systematic review and meta-analysis.

Rosiglitazone (Avandia) and pioglitazone (Actos) belong to the class of thiazolidinediones (TZDs) drugs that act by increasing insulin sensitivity and are widely used for treating diabetic patients with insulin resistance. TZDs exhibit anti-inflammatory and antioxidant properties, then may play an active role in inhibiting plaque formation and coronary atherosclerosis. But the results of evidence-based medicine suggest that TZDs may increase the risk of cardiovascular adverse events. To explore the dispute in depth, our meta-analysis aimed to evaluate the changes in vascular endothelial and plaque-related indicators following treatment with TZDs in diabetic patients with coronary atherosclerosis. According to our meta-analysis, TZDs showed an inhibiting effect on plaque progression and a protective effect on the vascular endothelium in patients with diabetes and coronary atherosclerosis. Interestingly, these effects may not depend on the regulation of inflammation and lipid metabolism. By this token, TZDs may develop a potential protective effect on myocardial infarction. Systematic review registration: [https://www.crd.york.ac.uk/prospero/], identifier [CRD42021231663].

[Effect of Er:YAG laser in pulp revascularization in miniature pigs].

PURPUSE: To compare the effectiveness of Er:YAG laser and Ca(OH)2 in pulp revascularization in miniature pigs. METHODS: The second and third premolars of three 14-15-month-old miniature pigs were randomly divided into three groups: laser group, medication group and negative control group. After establishment of pulp necrosis model in each group, the negative control group had no more procedures, while the laser group and medication group were treated with pulp revascularization. Intracanal antisepsis operation was conducted using Er:YAG laser in laser group and Ca(OH)2 in medication group. The maxillary first premolars, as a positive control group, were left untreated and grew naturally. Three months after surgery, X-ray and cone-beam CT(CBCT) were taken. The animals were sacrificed, and the teeth were used to make H-E staining sections. The development of the teeth and the histological manifestations in the root canals of both groups were compared and evaluated by radiographic and histological assessment. SPSS 24.0 software package was used for statistical analysis of the data. RESULTS: Radiographic results showed that 3 months after surgery, apical foramen was closed in the laser group and the medication group. It also showed that intracanal calcification, and some specimens manifested root absorption. There was no significant difference between the two groups in the aspects of increase of root length, root thickness, or decrease of apical foramen size(P>0.05). Histological results showed that there was dentin-like and cementum-like tissue deposition along the root canal walls; apical closure was apparent; and fibrous connective tissue and cementum-like tissue or bone-like tissue formation in the root canal space were evident in the laser group and the medication group 3 months after surgery. There was no significant difference in the histological findings between the two groups(P>0.05). CONCLUSIONS: Er: YAG laser can be applied to pulp revascularization in miniature pigs, and the effect is equivalent to that of intracanal medication using Ca(OH)2.

Mitochondrial Dysfunction and Diabetic Nephropathy: Nontraditional Therapeutic Opportunities.

Diabetic nephropathy (DN) is a progressive microvascular diabetic complication. Growing evidence shows that persistent mitochondrial dysfunction contributes to the progression of renal diseases, including DN, as it alters mitochondrial homeostasis and, in turn, affects normal kidney function. Pharmacological regulation of mitochondrial networking is a promising therapeutic strategy for preventing and restoring renal function in DN. In this review, we have surveyed recent advances in elucidating the mitochondrial networking and signaling pathways in physiological and pathological contexts. Additionally, we have considered the contributions of nontraditional therapy that ameliorate mitochondrial dysfunction and discussed their molecular mechanism, highlighting the potential value of nontraditional therapies, such as herbal medicine and lifestyle interventions, in therapeutic interventions for DN. The generation of new insights using mitochondrial networking will facilitate further investigations on nontraditional therapies for DN.

[Histological evaluations on periapical tissues after irradiation by erbium-doped yttrium aluminum garnet laser in Labradors dogs].

PURPOSE: To investigate the thermal effects on periapical tissues of Labrador dogs after intra-canal irradiation by erbium-doped yttrium aluminum garnet (Er:YAG) laser at different powers based on the antibacterial experiment of Enterococcus faecalis and Escherichia coli in root canals with an isthmus, to assess the histological changes, and to prove the safety for clinical applications. METHODS: Two hundred root canals of 10 healthy adult Labradors dogs were selected and divided into 5 groups. Excepted one as control group, root canals in other 4 groups were irradiated by Er:YAG laser with 1.5, 2.0, 2.5, 3.0 W for 30 s. Ten Labradors dogs were sacrificed at 0 (immediately after irradiation), 2 days, 2 weeks, 1 and 2 months. After preparation of pathological specimen, histological changes after laser irradiation in periapical tissues were evaluated and scores of inflammation were graded. Statistical analysis was performed using SPSS 13.0 software package. RESULTS: No significant difference was observed at the apical area between 1.5, 2.0, 2.5 W and control groups at most periods (P>0.05), whereas significant difference was observed between 3.0 W and other groups for all periods (P<0.05). CONCLUSIONS: These results suggest that if proper output powers (2.0-2.5 W) of laser irradiation are chosen, disinfection in root canals can be finished successfully and thermal effects on the periapical tissues can be minimized.

[Evaluation of root canal isthmus debridement efficacy of Er:YAG laser in combination with sodium hypochlorite].

PURPOSE: To histologically evaluate the efficacy of sodium hypochlorite (NaClO) in combination with Er:YAG (erbium-doped yttrium aluminium garnet) laser in dissolving necrotic tissue and cleaning root canals as well as canal isthmuses. METHODS: After scanned by cone-beam CT (CBCT), 50 well-prepared premolars with root canal isthmuses were selected and randomly assigned into 5 groups. They were subsequently subjected to different regimens as followed: group A-irrigated with 1% NaClO for 1 minute, group B- irradiated by Er:YAG laser at 0.5 W combined with 1% NaClO irrigation for 1 minute, group C- irradiated by Er:YAG laser at 1.0 W combined with 1% NaClO irrigation for 1 minute, group D- irradiated by Er:YAG laser at 2.0 W combined with 1% NaClO irrigation for 1 minute,group E- negative control. After histological preparation and staining, the cross-sections were evaluated for percentage of tissue removal from root canals and isthmuses. The cleanliness values were calculated using SPSS 13.0 software package. RESULTS: The mean percentage of root canals in group A, B, C and D was 95.24%, 96.53%、97.63% and 98.22%, respectively, and the mean percentage of isthmuses was 16.50%, 51.48%, 52.56% and 53.83%, respectively. The mean percentage of root canal and isthmus cleanliness values were significantly higher in group B, C and D (P<0.05) than that in group A. There was no significant differences of root canal and isthmus cleanliness among group B, C and D. CONCLUSIONS: Er:YAG laser combined with 1% NaClO irrigation may be used effectively in root canal and root canal isthmus cleanliness as a new method.

[Application of robots in stomatology].

Recently, the robot technology has been developed rapidly and the medical robot has been used in many clinical areas, especially in the field of stomatology. The application of robot in stomatology will break the traditional mode of treatment and bring a new technological revolution. This paper introduced the advantages, the current situation and the development prospect of applying robot in stomatology.