Interpenetrating nanofibrillar membrane of self-assembled collagen and antimicrobial peptides for enhanced bone regeneration.

Bone regeneration remains a major clinical challenge, especially when infection necessitates prolonged antibiotic treatment. This study presents a membrane composed of self-assembled and interpenetrating GL13K, an antimicrobial peptide (AMP) derived from a salivary protein, in a collagen membrane for antimicrobial activity and enhanced bone regeneration. Commercially available collagen membranes were immersed in GL13K solution, and self-assembly was initiated by raising the solution pH to synthesize the multifunctional membrane called COL-GL. COL-GL was composed of interpenetrating large collagen fibers and short GL13K nanofibrils, which increased hydrophobicity, reduced biodegradation from collagenase, and stiffened the matrix compared to control collagen membranes. Incorporation of GL13K led to antimicrobial and anti-fouling activity against early oral surface colonizer Streptococcus gordonii while not affecting fibroblast cytocompatibility or pre-osteoblast osteogenic differentiation. GL13K in solution also reduced macrophage inflammatory cytokine expression and increased pro-healing cytokine expression. Bone formation in a rat calvarial model was accelerated at eight weeks with COL-GL compared to the gold-standard collagen membrane based on microcomputed tomography and histology. Interpenetration of GL13K within collagen sidesteps challenges with antimicrobial coatings on bone regeneration scaffolds while increasing bone regeneration. This strength makes COL-GL a promising approach to reduce post-surgical infections and aid bone regeneration in dental and orthopedic applications. STATEMENT OF SIGNIFICANCE: The COL-GL membrane, incorporating the antimicrobial peptide GL13K within a collagen membrane, signifies a noteworthy breakthrough in bone regeneration strategies for dental and orthopedic applications. By integrating self-assembled GL13K nanofibers into the membrane, this study successfully addresses the challenges associated with antimicrobial coatings, exhibiting improved antimicrobial and anti-fouling activity while preserving compatibility with fibroblasts and pre-osteoblasts. The accelerated bone formation observed in a rat calvarial model emphasizes the potential of this innovative approach to minimize post-surgical infections and enhance bone regeneration outcomes. As a promising alternative for future therapeutic interventions, this material tackles the clinical challenges of extended antibiotic treatments and antibiotic resistance in bone regeneration scenarios.

Regulatory role of PDK1 via integrated gene analysis of mitochondria-immune response in periodontitis.

AIMS: To investigate the association between mitochondrial events and immune response in periodontitis and related regulatory genes. MAIN METHODS: Gene expression profiles in gingival tissues were retrieved from the Gene Expression Omnibus. Mitochondria-immune response-related differentially expressed genes (MIR-DEGs) between the healthy and periodontitis samples were determined. WGCNA, GO, and KEGG were used to investigate the function and the enriched pathways of MIR-DEGs. The correlation between MIR-DEGs expression and clinical probing pocket depth was analyzed. The MIR-DEGs were further identified and verified in animal samples. A periodontitis model was established in C57BL/6 mice with silk ligation. Micro-computed tomography was used to assess alveolar bone loss. Western blot, quantitative real-time polymerase chain reaction, and immunohistochemical analyses further validated the differential expression of the MIR-DEGs. KEY FINDINGS: A total of ten MIR-DEGs (CYP24A1, PRDX4, GLDC, PDK1, BCL2A1, CBR3, ARMCX3, BNIP3, IFI27, and UNG) were identified, the expression of which could effectively distinguish patients with periodontitis from the healthy controls. Enhanced immune response was detected in the periodontitis group with that in the healthy controls, especially in B cells. PDK1 was a critical MIR-DEG correlated with B cell immune response and clinical periodontal probing pocket depth. Both animal and clinical periodontal samples presented higher gene and protein expression of PDK1 than the control samples. Additionally, PDK1 colocalized with B cells in both animal and clinical periodontal tissues. SIGNIFICANCE: Mitochondria participate in the regulation of the immune response in periodontitis. PDK1 may be the key mitochondria-related gene regulating B-cell immune response in periodontitis.

Design, Synthesis, and Biological Evaluation of ß-Trifluoroethoxydimethyl Selenides as Potent Antiosteoporosis Agents.

An efficient protocol for the synthesis of ß-trifluoroethoxydimethyl selenides was achieved under mild reaction conditions, and 39 compounds were prepared. All compounds were evaluated for their abilities to inhibit RANKL-induced osteoclastogenesis, compound 4aa exhibited the most potent activity. Further investigations revealed that 4aa could inhibit F-actin ring generation, bone resorption, and osteoclast-specific gene expression in vitro. Western blot analyses demonstrated that compound 4aa abrogated the RANKL-induced mitogen-activated protein kinase and NF-kB-signaling pathways. In addition, 4aa also displayed a notable impact on the osteoblastogenesis of MC3T3-E1 preosteoblasts. In vivo experiments revealed that compound 4aa significantly ameliorated bone loss in an ovariectomized (OVX) mice model. Furthermore, the surface plasmon resonance experiment results revealed that 4aa probably bound to RANKL. Collectively, the above-mentioned findings suggested that compound 4aa as a potential RANKL inhibitor averted OVX-triggered osteoporosis by regulating the inhibition of osteoclast differentiation and stimulation of osteoblast differentiation.

The role of oxidative stress biomarkers in the development of peri-implant disease: A systematic review and meta-analysis.

OBJECTIVES: To analyze the role of oxidative stress (OS) biomarkers in peri­implant diseases using a systematic review and meta-analysis approach. DATE: The review incorporated cross-sectional studies, randomized controlled trials, and case-control trials to evaluate the differences in OS biomarkers of peri­implant disease. SOURCES: A comprehensive literature search was conducted in electronic databases such as PubMed, Scopus, Embase, Web of Science, and CNKI, and no restrictions were applied during the search process. STUDY SELECTION: A total of 452 studies were identified, of which 18 were eligible for inclusion. Risk of bias and sensitivity analysis were assessed using Egger's test and funnel plots. RESULTS: We found that the levels of glutathione peroxidase (GSH-Px) in the peri­implant sulcus fluid (PISF) of patients with peri­implant diseases were significantly reduced (SMD = -1.40; 95 % CI = 1.70, -1.11; p < 0.001), while the levels of total myeloperoxidase (MPO) and malondialdehyde (MDA) were significantly increased (SMD = 0.46; 95 % CI = 0.12, 0.80; p = 0.008; SMD = 0.28; 95 % CI = 0.01, 0.56; p = 0.043). However, there were no significant differences of MPO concentration (SMD = 0.38; 95 % CI = -0.39, 1.15; p = 0.331) and superoxide dismutase (SOD)(SMD = -0.43; 95 % CI = -1.94, 1.07; p = 0.572) in PISF between peri­implant disease group and control group. Similarly, salivary MPO did not show significant differences (SMD = 1.62; 95 % CI = -1.01, 4.24; p = 0.227). CONCLUSIONS: Our results supported that the level of local OS biomarkers was closely related to peri­implant diseases. GSH-Px, total MPO and MDA may be PISF biomarkers with good capability to monitor the development of peri­implant disease. CLINICAL SIGNIFICANCE: This study found significant differences in the levels of local OS biomarkers (GSH-Px, total MPO, and MDA) between patients with peri­implant diseases and healthy subjects, which may be ideal candidate biomarkers for predicting and diagnosing peri­implant diseases.

Biodegradable Zn-5Dy Alloy with Enhanced Osteo/Angio-Genic Activity and Osteointegration Effect via Regulation of SIRT4-Dependent Mitochondrial Function.

Zinc (Zn)-dysprosium (Dy) binary alloys are promising biodegradable bone fracture fixation implants owing to their attractive biodegradability and mechanical properties. However, their clinical application is a challenge for bone fracture healing, due to the lack of Zn-Dy alloys with tailored proper bio-mechanical and osteointegration properties for bone regeneration. A Zn-5Dy alloy with high strength and ductility and a degradation rate aligned with the bone remodeling cycle is developed. Here, mechanical stability is further confirmed, proving that Zn-5Dy alloy can resist aging in the degradation process, thus meeting the mechanical requirements of fracture fixation. In vitro cellular experiments reveal that the Zn-5Dy alloy enhances osteogenesis and angiogenesis by elevating SIRT4-mediated mitochondrial function. In vivo Micro-CT, SEM-EDS, and immunohistochemistry analyses further indicate good biosafety, suitable biodegradation rate, and great osteointegration of Zn-5Dy alloy during bone healing, which also depends on the upregulation of SIRT4-mediated mitochondrial events. Overall, the study is the first to report a Zn-5Dy alloy that exerts remarkable osteointegration properties and has a strong potential to promote bone healing. Furthermore, the results highlight the importance of mitochondrial modulation and shall guide the future development of mitochondria-targeting materials in enhancing bone fracture healing.

[Effects of mechanical cardiopulmonary resuscitation during vertical spatial pre-hospital transport in patients with cardiac arrest: a historical cohort study].

OBJECTIVE: To analyze the effect of mechanical cardiopulmonary resuscitation (CPR) on patients with cardiac arrest with the vertical spatial pre-hospital emergency transport. METHODS: A retrospective cohort study was conducted. The clinical data of 102 patients with out-of-hospital cardiac arrest (OHCA) who were transferred to the emergency medicine department of Huzhou Central Hospital from the Huzhou Emergency Center from July 2019 to June 2021 were collected. Among them, the patients who performed artificial chest compression during the pre-hospital transfer from July 2019 to June 2020 served as the control group, and the patients who performed artificial-mechanical chest compression (implemented artificial chest compression first, and implemented mechanical chest compression immediately after the mechanical chest compression device was ready) during pre-hospital transfer from July 2020 to June 2021 served as the observation group. The clinical data of patients of the two groups were collected, including basic data (gender, age, etc.), pre-hospital emergency process evaluation indicators [chest compression fraction (CCF), total CPR pause time, pre-hospital transfer time, vertical spatial transfer time], and in-hospital advanced resuscitation effect evaluation indicators [initial end-expiratory partial pressure of carbon dioxide (PETCO2), rate of restoration of spontaneous circulation (ROSC), time of ROSC]. RESULTS: Finally, a total of 84 patients were enrolled, including 46 patients in the control group and 38 in the observation group. There was no significant difference in gender, age, whether to accept bystander resuscitation or not, initial cardiac rhythm, time-consuming pre-hospital emergency response, floor location at the time of onset, estimated vertical height, and whether there was any vertical transfer elevator/escalator, etc. between the two groups. In the evaluation of the pre-hospital emergency process, the CCF during the pre-hospital emergency treatment of patients in the observation group was significantly higher than that in the control group [69.05% (67.35%, 71.73%) vs. 61.88% (58.18%, 65.04%), P < 0.01], the total pause time of CPR was significantly shorter than that in the control group [s: 266 (214, 307) vs. 332 (257, 374), P < 0.05]. However, there was no significant difference in the pre-hospital transfer time and vertical spatial transfer time between the observation group and the control group [pre-hospital transfer time (minutes): 14.50 (12.00, 16.75) vs. 14.00 (11.00, 16.00), vertical spatial transfer time (s): 32.15±17.43 vs. 27.96±18.67, both P > 0.05]. It indicated that mechanical CPR could improve the CPR quality in the process of pre-hospital first aid, and did not affect the transfer of patients by pre-hospital emergency medical personnel. In the evaluation of the in-hospital advanced resuscitation effect, the initial PETCO2 of the patients in the observation group was significantly higher than that of the patients in the control group [mmHg (1 mmHg ≈ 0.133 kPa): 15.00 (13.25, 16.00) vs. 12.00 (11.00, 13.00), P < 0.01], the time of ROSC was significantly shorter than that in the control group (minutes: 11.00±3.25 vs. 16.64±2.54, P < 0.01), and the rate of ROSC was slightly higher than that in the control group (31.58% vs. 23.91%, P > 0.05). It indicated that continuous mechanical compression during pre-hospital transfer helped to ensure continuous high-quality CPR. CONCLUSIONS: Mechanical chest compression can improve the quality of continuous CPR during the pre-hospital transfer of patients with OHCA, and improve the initial resuscitation outcome of patients.

Case report: Five-year periodontal management of a patient with two novel mutation sites in ELANE-induced cyclic neutropenia.

Cyclic neutropenia (CyN) is a rare, ELANE-related neutropenia. Oral manifestations are among the initial signs of CyN and an important reason that leads patients to seek professional help. This case report describes a 12-year-old girl with recurrent oral ulcers, severe chronic periodontitis, and pathological tooth migration as the initial and main clinical symptoms of CyN. Two novel mutations in ELANE, c.180T>G (p.I60M) and c.182C>G (p.A61G) associated with CyN were observed. Bioinformatics research indicated lower stability and impaired molecular linkages of the mutant neutrophil elastase (NE) encoded by ELANE. However, the enzyme affinity to the classic substrate Suc-Ala-Ala-Ala-pNA was not substantially changed, suggesting that the impaired integrity and stability of the mutant NE, rather than catalytic deficiency, might be the pathogenic mechanism of ELANE mutation-induced neutropenia. The patient was prescribed scaling and root planing (SRP) and monthly periodontal maintenance without systemic management. Although the routine periodontal treatment was occasionally interrupted by the 2019 coronavirus pandemic, her periodontal devastation remained well-remitted in the 5-year follow-up assessment. The results of this study confirmed the importance of plaque control and proper diagnosis in the periodontal management of such patients and provide better clinical references. In addition, the novel mutations identified in this study expand the spectrum of known ELANE mutations in CyN and further contribute to knowledge regarding its pathogenic mechanism.

A history of cigarette smoking is associated with faster functional decline and reduction of entorhinal cortex volume in mild cognitive impairment.

Little is known about the longitudinal association of cigarette smoking with Alzheimer's Disease (AD) related markers in subjects with mild cognitive impairment (MCI). In this study, we aimed to examine the effect of a history of cigarette smoking on change in global cognition, verbal memory, functional performance, hippocampal volume, entorhinal cortex volume, brain glucose metabolism, and CSF AD pathologies over time in MCI subjects. At baseline, there were 870 subjects with MCI, including 618 non-smokers (no history of smoking) and 252 smokers (any lifetime history of smoking). Linear mixed models were fitted for each outcome with adjustment of several covariates. The major findings were: (1) Among older people with MCI, smokers showed faster decline in functional performance compared to non-smokers; (2) Smokers demonstrated steeper decline in entorhinal cortex volume than non-smokers; (3) A history of cigarette smoking was not associated with change in CSF Aß42, t-tau or p-tau levels over time in MCI subjects. In conclusion, we found that a history of cigarette smoking was associated with faster decline in functional performance and entorhinal cortex volume over time at the prodromal stage of dementia.