BACKGROUND: Diabetic foot is a complex condition with high incidence, recurrence, mortality, and disability rates. Current treatments for diabetic foot ulcers are often insufficient. This study was conducted to identify potential therapeutic targets for diabetic foot. METHODS: Datasets related to diabetic foot and diabetic skin were retrieved from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified using R software. Enrichment analysis was conducted to screen for critical gene functions and pathways. A protein interaction network was constructed to identify node genes corresponding to key proteins. The DEGs and node genes were overlapped to pinpoint target genes. Plasma and chronic ulcer samples from diabetic and non-diabetic individuals were collected. Western blotting, immunohistochemistry, and enzyme-linked immunosorbent assays were performed to verify the S100 calcium binding protein A9 (S100A9), inflammatory cytokine, and related pathway protein levels. Hematoxylin and eosin staining was used to measure epidermal layer thickness. RESULTS: In total, 283 common DEGs and 42 node genes in diabetic foot ulcers were identified. Forty-three genes were differentially expressed in the skin of diabetic and non-diabetic individuals. The overlapping of the most significant DEGs and node genes led to the identification of S100A9 as a target gene. The S100A9 level was significantly higher in diabetic than in non-diabetic plasma (178.40 ± 44.65 ng/mL vs. 40.84 ± 18.86 ng/mL) and in chronic ulcers, and the wound healing time correlated positively with the plasma S100A9 level. The levels of inflammatory cytokines (tumor necrosis factor-α, interleukin [IL]-1, and IL-6) and related pathway proteins (phospho-extracellular signal regulated kinase [ERK], phospho-p38, phospho-p65, and p-protein kinase B [Akt]) were also elevated. The epidermal layer was notably thinner in chronic diabetic ulcers than in non-diabetic skin (24.17 ± 25.60 μm vs. 412.00 ± 181.60 μm). CONCLUSIONS S100A9 was significantly upregulated in diabetic foot and was associated with prolonged wound healing. S100A9 may impair diabetic wound healing by disrupting local inflammatory responses and skin re-epithelialization.
Calgranulin B/therapeutic use* ; Diabetic Foot/metabolism* ; Humans ; Datasets as Topic ; Computational Biology ; Mice, Inbred C57BL ; Animals ; Mice ; Protein Interaction Maps ; Immunohistochemistry

Sini Decoction (SNT) is a traditional formula recognized for its efficacy in warming the spleen and stomach and dispersing cold. However, elucidating the mechanism of action of SNT remains challenging due to its complex multiple components. This study utilized a synergistic approach combining two-dimensional fluorescence difference in gel electrophoresis (2D-DIGE)-based drug affinity responsive target stability (DARTS) with label-free quantitative proteomics techniques to identify the direct and indirect protein targets of SNT in myocardial infarction. The analysis identified 590 proteins, with 30 proteins showing significant upregulation and 51 proteins showing downregulation when comparing the SNT group with the model group. Through the integration of 2D-DIGE DARTS with proteomics data and pharmacological assessments, the findings indicate that protein disulfide-isomerase A3 (PDIA3) may serve as a potential protein target through which SNT provides protective effects on myocardial cells during myocardial infarction.
Myocardial Infarction/genetics* ; Proteomics/methods* ; Drugs, Chinese Herbal/chemistry* ; Animals ; Protein Disulfide-Isomerases/genetics* ; Male ; Two-Dimensional Difference Gel Electrophoresis/methods* ; Humans ; Rats ; Rats, Sprague-Dawley ; Electrophoresis, Gel, Two-Dimensional

The properties of adhesives and light-cured resin composites are closely related to the repair of dental defects. Therefore, improving the properties of adhesives and resins composite to increase the success rate of filling has been the focus of research in the field of prosthodontics in recent years. Current studies have confirmed that temperature can change the properties of adhesives and light-cured resin composites, affecting their repair effect. A proper storage temperature ensures the good performance of materials: the self-etching adhesive system should be refrigerated, and the light-cured resin composite should be refrigerated or stored at room temperature according to its composition, proportion and other properties; however, the appropriate storage temperature for the etch-and-rinse adhesive system is not clear. The appropriate application temperature could improve the fluidity, monomer conversion, bonding strength, compressive strength and other properties of the materials to improve the quality of filling restoration. However, there is a wide variety of adhesives and resin composites, and the effect of temperature on each material is different. Thus, it is still necessary to explore the temperature range for material storage, precooling and preheating. Few studies have been performed in vivo, and the clinical restorative effects of adhesives and resin composites stored and used at different temperatures need to be further studied.

RAS, a member of the small GTPase family, functions as a binary switch by shifting between inactive GDP-loaded and active GTP-loaded state. RAS gain-of-function mutations are one of the leading causes in human oncogenesis, accounting for ∼19% of the global cancer burden. As a well-recognized target in malignancy, RAS has been intensively studied in the past decades. Despite the sustained efforts, many failures occurred in the earlier exploration and resulted in an 'undruggable' feature of RAS proteins. Phosphorylation at several residues has been recently determined as regulators for wild-type and mutated RAS proteins. Therefore, the development of RAS inhibitors directly targeting the RAS mutants or towards upstream regulatory kinases supplies a novel direction for tackling the anti-RAS difficulties. A better understanding of RAS phosphorylation can contribute to future therapeutic strategies. In this review, we comprehensively summarized the current advances in RAS phosphorylation and provided mechanistic insights into the signaling transduction of associated pathways. Importantly, the preclinical and clinical success in developing anti-RAS drugs targeting the upstream kinases and potential directions of harnessing allostery to target RAS phosphorylation sites were also discussed.

Objective    To explore the feasibility of goat tricuspid regurgitation (TR) model by one chordae tendineae cutter via right anterior-lateral minimal incision. Methods    TR model was established in 6 goats with a self-made tricuspid valve chordae tendineae cutter. The goats were placed in a left lateral position and procedure was performed via a right anterior-lateral minimal thoracotomy in the fourth intercostal. Under the guidance of transesophageal ultrasound and digital subtraction angiography, the chordae tendineae of anterior leaflet was cut until moderate to severe regurgitation was confirmed. Echocardiography and laboratory examinations were performed preoperatively, immediately and 3 months after surgery. Additionally, all goats were sacrificed to clarify pathological evaluation. Results    TR was successfully established in 6 goats. The right atrium pressure increased significantly immediately after surgery (P<0.05). During a follow-up of 3 months, the progression of TR was aggravated (P<0.05), and the annular diameter increased from 2.15±0.23 cm to 2.65±0.20 cm. Overall, there was no statistically significant change in transvalvular gradient and velocity between preoperation and postoperation. Laboratory test results showed no abnormalities between preoperation and postoperation. Autopsy evaluation demonstrated obvioue chordae tendineae transection of the anterior leaflet. Conclusion    It is feasible to establish TR model via a right minimal anterior lateral thoracotomy in the fourth intercostal space. This novel TR goats model will allow investigation of transcatheter interventional device and serve as a chronic model in the future.

Recently, several transcatheter devices for aortic valve replacement and mitral valve repair have been used in clinic, and researchers have designed a variety of tricuspid valve (TV) intervention devices. We reviewed the current status of transcatheter TV intervention, and focused on the structures of these devices and the early results of clinical trials. Undoubtedly, transcatheter intervention for TV is promising, innovational and safe for patients with severe TV regurgitation.

Dens in dente is a rare malformation of teeth.This article reports one case of type Ⅲ dens in dente of maxillary bilateral incisors with acute periapical lesion.The case was treated successfully by apexification with Vitapex paste.

Objective To establish the golden hamster model of buccal squamous carcinoma and observe its biological character-istics .Methods 50 golden hamster were randomly divided into two group :experiment group (n=40) and control group(n=10) . Buccal mucosa of golden hamster were daubed by exposure 4-nitroquinoline-1-oxide (4NQO) in experiment group and tap water in control group .HE staining and immunohistochemistry were used to observe the tissue sample on the 8th and 12th week .The tissue samples of golden hamster buccal-mucosa cancer were used for the in-vitro subculture .Then flat cloning formation rate ,expression of CK and Vim ,and cell karyotype were detected .Results The observations of cell morphology and biology showed that the tissue of buccal squamous carcinoma were conformed to the basic characteristics of squamous carcinoma cell in 26 golden hamster(84 .6% ) after 12 weeks .The positive rate of CK and Vim were 96 .0% by immunohistochemical staining .The Chromosomes were tetraploid karyotype .Conclusion We successfully established the golden hamster model of buccal squamous carcinoma by the daub method of 4NQO .