X-ray linear dichroic ptychography.

Biominerals such as seashells, coral skeletons, bone, and tooth enamel are optically anisotropic crystalline materials with unique nanoscale and microscale organization that translates into exceptional macroscopic mechanical properties, providing inspiration for engineering new and superior biomimetic structures. Using Seriatopora aculeata coral skeleton as a model, here, we experimentally demonstrate X-ray linear dichroic ptychography and map the c-axis orientations of the aragonite (CaCO3) crystals. Linear dichroic phase imaging at the oxygen K-edge energy shows strong polarization-dependent contrast and reveals the presence of both narrow (<35°) and wide (>35°) c-axis angular spread in the coral samples. These X-ray ptychography results are corroborated by four-dimensional (4D) scanning transmission electron microscopy (STEM) on the same samples. Evidence of co-oriented, but disconnected, corallite subdomains indicates jagged crystal boundaries consistent with formation by amorphous nanoparticle attachment. We expect that the combination of X-ray linear dichroic ptychography and 4D STEM could be an important multimodal tool to study nano-crystallites, interfaces, nucleation, and mineral growth of optically anisotropic materials at multiple length scales.

A Water-Based Biocoating to Increase the Infection Resistance and Osteoconductivity of Titanium Surfaces.

As the population ages, the number of patients undergoing total hip arthroplasty (THA) and total knee arthroplasty (TKA) continues to increase. Infections after primary arthroplasty are rare but have high rates of morbidity and mortality, as well as enormous financial implications for healthcare systems. Numerous methods including the use of superhydrophobic coatings, the incorporation of antibacterial agents, and the application of topographical treatments have been developed to reduce bacterial attachment to medical devices. However, most of these methods require complex manufacturing processes. Thus, the main purpose of this study was to apply biocoatings to titanium (Ti) surfaces to increase their infection resistance and osteoconductivity via simple processes, without organic reagents. We modified titanium surfaces with a combination of aminomalononitrile (AMN) and an antibiotic-loaded mesoporous bioactive glass (MBG) and evaluated both the antibacterial effects of the coating layer and its effect on osteoblast proliferation and differentiation. The properties of the modified surface, such as the hydrophilicity, roughness, and surface morphology, were characterized via contact angle measurements, atomic force microscopy, and scanning electron microscopy. The cell proliferation reagent WST-1 assay and the alkaline phosphatase (ALP) assay were used to determine the degrees of adhesion and differentiation, respectively, of the MG-63 osteoblast-like cells on the surface. Antimicrobial activity was evaluated by examining the survival rate and inhibition zone of Escherichia coli (E. coli). The AMN coating layer reduced the water contact angle (WCA) of the titanium surface from 87° ± 2.5° to 53° ± 2.3° and this change was retained even after immersion in deionized water for five weeks, demonstrating the stability of the AMN coating. Compared with nontreated titanium and polydopamine (PDA) coating layers, the AMN surface coating increased MG-63 cell attachment, spreading, and early ALP expression; reduced E. coli adhesion; and increased the percentage of dead bacteria. In addition, the AMN coating served as an adhesion layer for the subsequent deposition of MBG-containing antibiotic nanoparticles. The synergistic effects of the AMN layer and antibiotics released from the MBG resulted in an obvious E. coli inhibition zone that was not observed in the nontreated titanium group.

Augmented Reality in Spine Surgery: A Case Study of Atlantoaxial Instrumentation in Os Odontoideum.

Despite advancement in surgical innovation, C1-C2 fixation remains challenging due to risks of screw malposition and vertebral artery (VA) injuries. Traditional image-based navigation, while useful, often demands that surgeons frequently shift their attention to external monitors, potentially causing distractions. In this article, we introduce a microscope-based augmented reality (AR) navigation system that projects both anatomical information and real-time navigation images directly onto the surgical field. In the present case report, we discuss a 37-year-old female who suffered from os odontoideum with C1-C2 subluxation. Employing AR-assisted navigation, the patient underwent the successful posterior instrumentation of C1-C2. The integrated AR system offers direct visualization, potentially minimizing surgical distractions. In our opinion, as AR technology advances, its adoption in surgical practices and education is anticipated to expand.

Light Scattering of Electrospinning Jet with Internal Structures by Flow-Induced Phase Separation.

Herein, the direct morphological evidence of the extension-induced phase-separated structures in the electrospinning jet observed by high-speed video imaging and by light scattering technique is reported. Model solutions of poly(vinyl alcohol) (PVA)/water are electrospun. Two types of internal structures, that is, long strings and short ellipsoids, are found. A light scattering model is derived for the Vv scattering configuration to account for the scattered intensities contributed from the liquid jet itself and those from the internal structures. For the severely stretching jet of PVA/water, the Vv intensity profile is dominant by the internal structures to mask the scattering contribution from the jet itself. Moreover, the Hv intensity profile reflects the anisotropy of the oriented chains parallel to the jet axis. For the 7 wt% solution, the derived extension rate in the vicinity of the Taylor cone apex is about 3420 s-1 , which is higher than the Rouse relaxation rate measured by rheometer. It is concluded that extension-induced phase separation of the single-phase PVA solution is likely to occur in Taylor-cone apex to trigger the self-assembly process for producing strings (and/or bulges) in the flowing jet, which eventually transform to become the nanofibers, after solvent removal, to be collected on the grounded collector.

Rutin alleviates bisphenol A-glycidyl methacrylate-induced generation of proinflammatory mediators through the MAPK and NF-κB pathways in macrophages.

Bisphenol A-glycidyl methacrylate (BisGMA) is a methacrylate monomer that is mainly used in three-dimensional structures to reconstruct dental and bony defects. BisGMA has toxic and proinflammatory effects on macrophages. Rutin is a natural flavonol glycoside that is present in various plants and has useful biological effects, such as anti-inflammatory, anticancer, and antioxidative effects. The aim of this study was to investigate the anti-inflammation of rutin in macrophages after exposure to BisGMA. Pretreatment of the RAW264.7 macrophage with rutin at 0, 10, 30, and 100 µM for 30 min before being incubated with BisGMA at 0 or 3 µM. Proinflammatory cytokines and prostaglandin (PG) E2 were detected by enzyme-linked immunosorbent assay (ELISA). Nitric oxide (NO) was detected by the Griess assay. Expression and phosphorylation of proteins were measured by Western blot assay. Pretreatment with rutin inhibited the BisGMA-induced generation of proinflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, and PGE2, in macrophages. Rutin also suppressed the BisGMA-induced secretion of NO and expression of inducible nitric oxide synthase (iNOS) in a concentration-dependent manner. Furthermore, rutin suppressed the mitogen-activated protein kinase (MAPK) phosphorylation in a concentration-dependent manner. Finally, rutin suppressed the BisGMA-induced phosphorylation of nuclear factor (NF)-κB p65 and degradation of inhibitor of κB (IκB). These results indicate that the concentration of rutin has an inhibitory effect on proinflammatory mediator generation, MAPK phosphorylation, NF-κB p65 phosphorylation, and IκB degradation. In conclusion, rutin is a potential anti-inflammatory agent for BisGMA-stimulated macrophages through NF-κB p65 phosphorylation and IκB degradation resulting from MAPK phosphorylation.

Aluminum Plasmonic Nanoclusters for Paper-Based Surface-Enhanced Raman Spectroscopy.

Although surface-enhanced Raman spectroscopy (SERS) can rapidly identify molecular fingerprints and has great potential for analysis, the need for delicate plasmonic substrates and complex laboratory instruments seriously limits its applicability for on-site detection. This paper describes the development of an inexpensive aluminum nanoparticle (AlNP)-decorated paper that functions as a facile SERS-based detection platform (Al-PSERS). Polydopamine-protected AlNPs were chemically synthesized and then simply drop-cast onto a hydrophobic cellulose paper, forming a monolayer AlNP cluster array. Because of the abundance of hot spots arising from the plasmonic clusters, the inherent quasi-three-dimensional structure of the cellulose fibers, and the concentration effect of the hydrophobic surface, the Al-PSERS provided significant enhancements to the signal of various analytes, measured using a portable 785 nm Raman spectrometer. Near-field optical simulations and experimental spectroscopic results revealed that the local electric fields and corresponding SERS signal intensities of the AlNP array exhibited clear particle-length and cluster-size dependencies. Therefore, the Al-PSERS could be optimized to provide high sensitivity (enhancement factor: 2 × 103) and excellent reproducibility (variation: 8.72%). Moreover, the optimal Al-PSERS was capable of detecting colorants and environmental pollutants; for example, the detection limits of allura red and benzo[a]pyrene reached as low as 3.5 and 0.15 ppm, respectively. Furthermore, the Al-PSERS could rapidly identify illegal (rhodamine B) and edible (allura red, erythrosine) colorants from a mixture of multiple colorants or from adulterated candies. Because it facilitates rapid detection, is of low cost, and has minimal technical requirements, Al-PSERS should be applicable to on-site detection in, for example, food inspection and environmental monitoring.

Fox (Vulpes vulpes) involvement identified in a series of cat carcass mutilations.

This study was designed to identify the cause of mutilation and death in 32 cats, part of a larger cohort found dead in Greater London, the United Kingdom, between 2016 and 2018. At the time, discussion in the media led to concerns of a human serial cat killer (dubbed The Croydon Cat Killer) pursuing domestic cats, causing a state of disquietude. Given the link between animal abuse and domestic violence, human intervention had to be ruled out. Using a combination of DNA testing, computed tomography imaging, and postmortem examination, no evidence was found to support any human involvement. Instead, a significant association between cat carcass mutilation and the presence of fox DNA was demonstrated. Gross examination identified shared characteristics including the pattern of mutilation, level of limb or vertebral disarticulation, wet fur, wound edges with shortened fur, and smooth or irregular contours, and marks in the skin, muscle, and bone consistent with damage from carnivore teeth. Together these findings supported the theory that the cause of mutilation was postmortem scavenging by red foxes (Vulpes vulpes). The probable cause of death was established in 26/32 (81%) carcasses: 10 were predated, 8 died from cardiorespiratory failure, 6 from blunt force trauma, one from ethylene glycol toxicity, and another from liver failure. In 6 carcasses a cause of death was not established due to autolysis and/or extensive mutilation. In summary, this study highlights the value of a multidisciplinary approach to fully investigate cases of suspected human-inflicted mutilation of animals.

A comparison of naloxegol versus alvimopan at the time of cystectomy and urinary diversion.

INTRODUCTION: The use of alvimopan at the time of cystectomy has been associated with improved perioperative outcomes. Naloxegol is a less costly alternative that has been used in some centers. This study aims to compare the perioperative outcomes of patients undergoing cystectomy with urinary diversion who receive the mu-opioid antagonist alvimopan versus naloxegol. MATERIALS AND METHODS: This was a retrospective review that included all patients who underwent cystectomy with urinary diversion at our institution between 2007-2020. Comparisons were made between patients who received perioperative alvimopan, naloxegol and no mu-opioid antagonist (controls). RESULTS: In 715 patients who underwent cystectomy, 335 received a perioperative mu-opioid antagonist, of whom 57 received naloxegol. Control patients, compared to naloxegol and alvimopan patients, experienced a significantly (p < 0.05) delayed return of bowel function (4.3 vs. 2.5 vs. 3.0 days) and longer hospital length of stay (7.9 vs. 7.5 vs. 6.5 days), respectively. The incidence of nasogastric tube use (14.2% vs. 12.5% vs. 6.5%) and postoperative ileus (21.6% vs. 21.1% vs. 13.3%) was also most common in the control group compared to the naloxegol and alvimopan cohorts, respectively. A multivariable analysis revealed that when comparing naloxegol and alvimopan, there was no difference in return of bowel function (OR 0.88, p = 0.17), incidence of postoperative ileus (OR 1.60, p = 0.44), or hospital readmission (OR 1.22, p = 0.63). CONCLUSIONS: Naloxegol expedites the return of bowel function to the same degree as alvimopan in cystectomy patients. Given the lower cost of naloxegol, this agent may be a preferable alternative to alvimopan.

Protective effect of wogonin on inflammatory responses in BisGMA-treated macrophages through the inhibition of MAPK and NFκB pathways.

Composites, resins, and sealants that are commonly used in orthopedics and dentistry are based on 2,2-bis[p-(2'-hydroxy-3'-methacryloxypropoxy)phenylene]propane (BisGMA), which induces proinflammatory responses in macrophages. The present study aimed to explore the anti-inflammatory responses of wogonin, which is a natural dihydroxyl flavonoid compound, in BisGMA-treated macrophages. According to the findings, wogonin exhibits anti-inflammatory, antiallergic, anticancer, and antioxidative properties. The generation of nitric oxide (NO) and the expression of inducible nitric oxide synthase (iNOS) were noted to be inhibited by wogonin in BisGMA-treated macrophages. Furthermore, the production of proinflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6 was reduced. In addition, BisGMA-induced nuclear factor (NF)-κB p65 phosphorylation and inhibitor of κB (IκB) degradation were inhibited. Finally, the BisGMA-induced phosphorylation of mitogen-activated protein kinases (MAPKs), including p38 MAPK, extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) was inhibited. All these effects were induced by wogonin in the macrophages in a concentration-dependent manner. Similar inhibitory effects of wogonin were observed on the production of NO and proinflammatory cytokines, expression of iNOS, phosphorylation of NF-κB p65 and MAPK, and degradation of IκB. These results indicated that rutin is a potential anti-inflammatory agent for BisGMA-treated macrophages that undergo NFκB p65 phosphorylation and IκB degradation through upstream MAPK phosphorylation. Therefore, wogonin inhibits BisGMA-induced proinflammatory responses in macrophages through the regulation of the NFκB pathway and its upstream factor, MAPK.

Protective Effect of Rutin on Triethylene Glycol Dimethacrylate-Induced Toxicity through the Inhibition of Caspase Activation and Reactive Oxygen Species Generation in Macrophages.

Rutin, also called quercetin-3-rhamnosyl glucoside, is a natural flavonol glycoside present in many plants. Rutin is used to treat various diseases, such as inflammation, diabetes, and cancer. For polymeric biomaterials, triethylene glycol dimethacrylate (TEGDMA) is the most commonly used monomer and serves as a restorative resin, a dentin bonding agent and sealant, and a bone cement component. Overall, TEGDMA induces various toxic effects in macrophages, including cytotoxicity, apoptosis, and genotoxicity. The aim of this study was to investigate the protective mechanism of rutin in alleviating TEGDMA-induced toxicity in RAW264.7 macrophages. After treatment with rutin, we assessed the cell viability and apoptosis of TEGDMA-induced RAW264.7 macrophages using an methylthiazol tetrazolium (MTT) assay and Annexin V-FITC/propidium iodide assay, respectively. Subsequently, we assessed the level of genotoxicity using comet and micronucleus assays, assessed the cysteinyla aspartate specific proteinases (caspases) and antioxidant enzyme (AOE) activity using commercial kits, and evaluated the generation of reactive oxygen species (ROS) using a dichlorodihydrofluorescein diacetate (DCFH-DA) assay. We evaluated the expression of heme oxygenase (HO)-1, the expression of nuclear factor erythroid 2 related factor (Nrf-2), and phosphorylation of AMP activated protein kinase (AMPK) using the Western blot assay. The results indicated that rutin substantially reduced the level of cytotoxicity, apoptosis, and genotoxicity of TEGDMA-induced RAW264.7 macrophages. Rutin also blocked the activity of caspase-3, caspase-8, and caspase-9 in TEGDMA-stimulated RAW264.7 macrophages. In addition, it decreased TEGDMA-induced ROS generation and AOE deactivation in macrophages. Finally, we found that TEGDMA-inhibited slightly the HO-1 expression, Nrf-2 expression, and AMPK phosphorylation would be revered by rutin. In addition, the HO-1 expression, Nrf-2 expression, and AMPK phosphorylation was enhanced by rutin. These findings indicate that rutin suppresses TEGDMA-induced caspase-mediated toxic effects through ROS generation and antioxidative system deactivation through the Nrf-2/AMPK pathway. Therefore, rutin has the potential to serve as a novel antitoxicity agent for TEGDMA in RAW264.7 macrophages.

One-Year Treatment Outcome of Profile Changes After Transcutaneous Maxillary Distraction Osteogenesis in Growing Children With Cleft Lip and Palate.

OBJECTIVE: To evaluate the long-term stability of LeFort I osteotomy followed by distraction osteogenesis with a transcutaneous rigid external device for the treatment of severe maxillary hypoplasia in patients with cleft lip and palate. PATIENTS AND METHODS: Nine patients with cleft lip and palate underwent rigid external distraction after a LeFort I osteotomy for maxillary advancement. Lateral cephalometric films were analyzed for assessment of treatment outcome and stability in 1 month, 6 months, and 1 year after distraction. RESULTS: Significant maxillary advancement was observed in the horizontal direction, with the anterior nasal spine (ANS) distance of the maxilla increasing by an average of 20.5 ± 5.1 mm after distraction. The ANS relapse rates in 6 months and 1 year were 8.7% and 12.8%, respectively. The mean inclination of upper incisors to the palatal plane was almost unchanged (before: 109.8° ± 6.6°; after: 108.9° ± 7.5°). The movement ratios at the nasal tip/ANS, soft tissue A point/A point, and the upper vermilion border/upper incisor edge were 0.36:1, 0.72:1, and 0.83:1, respectively. CONCLUSION: Considerable maxillary advancement was achieved with less change of incisors inclination after distraction. Moreover, the relapse rate after 1 year was minimal. The concave facial profile was improved as well as the facial balance and aesthetics.

Preparation of PMMA Electrospun Fibers Bearing Porphyrin Pendants and Photocatalytic Degradation of Organic Dyes.

Porphyrins have a large π-π conjugation force between molecules, and they are easy to aggregate in solution, which affects the photoelectric properties of porphyrins. Connecting porphyrins to polymer links through covalent bonds not only retains the mechanical properties and thermal stability of polymer materials, but also has the photoelectric properties and catalytic properties of porphyrins, which improves the availability of materials. In this study, first, a porphyrin ligand with double bonds in the side chain was designed and the corresponding copper and zinc complexes were synthesized by adjusting the metal ions in the center of the pyrrole ring. Then, the metalloporphyrin complexes were copolymerized with methyl methacrylate (MMA), and two metalloporphyrin/PMMA copolymers were obtained: CPTPPCu/PMMA and CPTPPZn/PMMA. The structure of the compounds was characterized by IR, 1H NMR, MS, and UV-Vis spectra. Metalloporphyrin/PMMA copolymers were prepared into electrospun fiber materials by electrospinning. The morphology of the composites was studied by SEM, and the thermal stability and optical properties of electrospun fibers were studied by TGA and FL. The catalytic activity of electrospun fiber materials for the degradation of organic dyes was studied. The results showed that the efficiency of the metalloporphyrin/PMMA copolymer in photocatalytic degradation of methylene blue (MB) was better than that of the PMMA electrospun fiber blended with metalloporphyrin.

Radiotherapy vs sequential pegaspargase, gemcitabine, cisplatin and dexamethasone and radiotherapy in newly diagnosed early natural killer/T-cell lymphoma: A randomized, controlled, open-label, multicenter study.

To compare the efficacy and safety of radiotherapy (RT) and chemotherapy of pegaspargase, gemcitabine, cisplatin and dexamethasone (DDGP) combined with RT in newly diagnosed stage I-II natural killer/T-cell lymphoma (NKTL), we designed a randomized, controlled, open-label, multicenter clinical trial. Data from 65 stage I-II NKTL patients whose diagnoses were confirmed using immunohistochemistry were enrolled from January 2011 to December 2013 in the First Affiliated Hospital of Zhengzhou University. Patients were randomly divided into the RT group (n = 35) and the DDGP combined with RT group (n = 30). There was a difference between the Eastern Cooperative Oncology Group (ECOG) score in the two arms (P = .013). The complete response rate (CRR) and objective response rate (ORR) of DDGP combined with RT group were superior to those in the RT group (CRR: 73.3% vs 48.6%; ORR: 83.3% vs 60.0%, respectively). The 5-year progression-free survival (PFS) rate and overall survival (OS) rate in the DDGP combined with RT group were higher than those in the RT group (82.9% vs 56.5% for PFS, P = .023; 85.7% vs 60.4% for OS, P = .040), and treatment methods and lactate dehydrogenase were independent risk factors. Myelosuppression (P < .001), gastrointestinal reactions (P < .001), abnormal liver function (P = .007), coagulation abnormalities (P < .001) and baldness (P < .001) were more likely to occur in the DDGP combined with RT group. In conclusion, DDGP combined with radiotherapy obviously obtained great efficacy and prolonged the survival time of patients, also the side effects were mild for stage I-II NKTL. This trial was registered at https://register.clinicaltrials.gov as #NCT01501136.

Long-term clinical benefit of Peg-IFNα and NAs sequential anti-viral therapy on HBV related HCC.

Analysis of the value of long-term antiviral therapy using sequential Peg-IFN therapy and nucleos(t)ide analogues (NAs) improves the prognosis of HBV-related HCC. HBV-related HCC patients were classified into sequential therapy with Peg-IFNα-2a and NAs, and NAs therapy alone. All patients were followed up for 5 years. The survival rate, HCC recurrence rate, Child-Pugh score, and side effects of drugs were evaluated. Firstly, the early and late cumulative survival rate was higher in patients receiving antiviral therapy compared with the control patients (p<0.05). Patients receiving sequential therapy with Peg-IFNα-2a and NAs showed a higher late cumulative survival rate and significantly reduced early and late recurrence rate, compared to those in the NA-alone group (p<0.05). Single NAs therapy only reduced the late recurrence rate in HCC-patients. Secondly, NAs therapy significantly increased the Child-Pugh score after five years of therapy (five-year therapy 7.03±1.50 vs. initial score 6.63±0.85; p<0.05), whereas the sequential therapy with Peg-IFNα-2a and NAs did not greatly alter the Child-Pugh score (6.88±1.26; p>0.05). Compared to the control patients, patients receiving antiviral therapy (NAs alone or sequential therapy with Peg-IFNα-2a and NAs) exhibited a significantly decreased Child-Pugh score (p<0.05). Compared to NAs alone, sequential therapy with Peg-IFNα-2a and NAs provided a more efficient strategy for improving both the five-year survival rate and the two-year or five-year recurrence rate in patients.

Rutin-protected BisGMA-induced cytotoxicity, genotoxicity, and apoptosis in macrophages through the reduction of the mitochondrial apoptotic pathway and induction of antioxidant enzymes.

Bisphenol-A-glycidyldimethacrylate (BisGMA) is a resin monomer frequently used in dentin restorative treatments. The leakage of BisGMA monomer from BisGMA-based polymeric resins can lead to cytotoxicity in macrophages. Rutin has various beneficial bioeffects, including antioxidation and antiinflammation. In this study, we found that pretreatment of RAW264.7 macrophages with rutin-inhibited cytotoxicity induced by BisGMA in a concentration-dependent manner. BisGMA-induced apoptosis, which was detected by levels of phosphatidylserine from the internal to the external membrane and formation of sub-G1, and genotoxicity, which was detected by cytokinesis-blocked micronucleus and single-cell gel electrophoresis assays, were inhibited by rutin in a concentration-dependent manner. Rutin suppressed the BisGMA-induced activation of caspase-3 and -9 rather than caspase-8. Rutin inhibited the activation of the mitochondrial apoptotic pathway, including cytochrome C release and mitochondria disruption, after macrophages were treated with BisGMA. Finally, BisGMA-induced reactive oxygen species (ROS) generation and antioxidant enzyme (AOE) deactivation could be reversed by rutin. Parallel trends were observed in the elevation of AOE activation and inhibition of ROS generation, caspase-3 activity, mitochondrial apoptotic pathway activation, and genotoxicity. These results suggested that rutin suppressed BisGMA-induced cytotoxicity through genotoxicity, the mitochondrial apoptotic pathway, and relatively upstream factors, including reduction of ROS generation and induction of AOE.

Initiating narrative medicine into dental education: Opportunity, change, and challenge.

Recently, the patient-centered and comprehensive dental treatment are emphasized as the same important competency as traditional clinical skill training in dental education. It is a silver lining to reorganize current dental education and redefine the role of dentistry to dentist, patient, and society. Narrative medicine has emerged as a variant from medical humanities and takes inspiration from philosophy, literature, poetry, art, ethics, and social sciences. Narrative medicine adds humanistic care with empathy and listening to patients in daily care. In this article, we introduce the definition of narrative medicine, the concept of narrative dentistry, implementation of narrative medicine into dental education, and challenges in initiating narrative dentistry. During the current COVID-19 pandemic, it also affords the opportunity to initiate narrative medicine into dental education, dentist could emerge to heal patient holistically, but not simply eliminate oral diseases.

Enhanced Platelet-Rich Plasma (ePRP) Stimulates Wound Healing through Effects on Metabolic Reprogramming in Fibroblasts.

As a source of growth factors for expediting wound healing and tissue regeneration, plasma-rich plasma (PRP) has been extensively applied in diverse fields including orthopaedics, ophthalmology, oral and maxillofacial surgery, dentistry, and gynaecology. However, the function of PRP in metabolic regulations remains enigmatic. A standardized method was devised herein to enrich growth factors and to lyophilize it as enhanced PRP (ePRP) powder, which could become ubiquitously available without mechanical centrifugation in clinical practice. To identify metabolic reprogramming in human dermal fibroblasts under ePRP treatment, putative metabolic targets were identified by transcriptome profiling and validated for their metabolic effects and mechanism. ePRP does not only promote wound healing but re-aligns energy metabolism by shifting to glycolysis through stimulation of glycolytic enzyme activity in fibroblasts. On the contrary, oxygen consumption rates and several mitochondrial respiration activities were attenuated in ePRP-treated fibroblasts. Furthermore, ePRP treatment drives the mitochondrial resetting by hindering the mitochondrial biogenesis-related genes and results in a dampened mitochondrial mass. Antioxidant production was further increased by ePRP treatment to prevent reactive oxygen species formation. Besides, ePRP also halts the senescence progression of fibroblasts by activating SIRT1 expression. Importantly, the glycolytic inhibitor 2-DG can completely reverse the ePRP-enhanced wound healing capacity, whereas the mitochondrial inhibitor oligomycin cannot. This is the first study to utilize PRP for comprehensively investigating its effects on the metabolic reprogramming of fibroblasts. These findings indicate that PRP's primary metabolic regulation is to promote metabolic reprogramming toward glycolytic energy metabolism in fibroblasts, preserving redox equilibrium and allowing anabolic pathways necessary for the healing and anti-ageing process.

IL-8 as a Potential Therapeutic Target for Periodontitis and Its Inhibition by Caffeic Acid Phenethyl Ester In Vitro.

Salivary levels of interleukin-8 (IL-8) are elevated in patients with periodontitis. Caffeic acid phenethyl ester (CAPE) improves the periodontal status in subjects. However, whether CAPE can reduce IL-8 expression is unclear. We collected saliva to determine proinflammatory cytokine levels and used subgingival calculus and surrounding tissues from patients with periodontitis for oral microbiota analysis via 16s ribosomal RNA gene sequencing. THP-1 cells were stimulated with sterile-filtered saliva from patients, and target gene/protein expression was assessed. IL-8 mRNA expression was analyzed in saliva-stimulated THP-1 cells treated with CAPE and the heme oxygenase-1 (HO-1) inhibitor tin-protoporphyrin (SnPP). In 72 symptomatic individuals, IL-8 was correlated with periodontal inflammation (bleeding on probing, r = 0.45; p < 0.001) and disease severity (bleeding on probing, r = 0.45; p < 0.001) but not with the four oral microbiota species tested. Reduced salivary IL-8 secretion was correlated with effective periodontitis treatment (r = 0.37, p = 0.0013). In THP-1 cells, saliva treatment induced high IL-8 expression and IKK2 and nuclear factor-κB (NF-κB) phosphorylation. However, the IKK inhibitor BMS-345541, NF-κB inhibitor BAY 11-7082, and CAPE attenuated saliva-induced IL-8 expression. CAPE induced HO-1 expression and inhibited IKK2, IκBα, and NF-κB phosphorylation. Blocking HO-1 decreased the anti-inflammatory activity of CAPE. The targeted suppression of IL-8 production using CAPE reduces inflammation and periodontitis.

Role of the cholesterol hydroxyl group in the chemical exchange saturation transfer signal at -1.6 ppm.

Chemical exchange saturation transfer (CEST) can provide metabolite-weighted images in the clinical setting; therefore, understanding the origin of each CEST signal is essential to revealing the changes in diseases at the molecular level, which would provide further insight for diagnoses and treatments. The CEST signal at -1.6 ppm is attributed to the choline methyl group of phosphatidylcholines. The methyl groups have no exchangeable protons, so the corresponding CEST signals must result from the relayed nuclear Overhauser effect (rNOE); however, the detailed mechanism remains unclear. Cholesterol is a major component of biological membranes, and its content is closely related to the dynamics and phases of these lipids. However, cholesterol has a hydroxyl group, which could participate in proton exchange to complete the rNOE process. In this study, we used liposomes containing cholesterol and its analogs (5α-cholestane and progesterone), which presumably have similar capabilities of influencing lipid bilayers, and found that the steroid hydroxyl group is the key to inducing the rNOE at -1.6 ppm. Our results suggest that the origin of the rNOE at -1.6 ppm likely requires an intermolecular NOE between the proton of the choline methyl group and that of the cholesterol hydroxyl group, and a chemical exchange between the cholesterol hydroxyl group and bulk water. However, the phenomenon in which the rNOE at -1.6 ppm appears when the cholesterol concentration is high seems to contradict the in vivo results, suggesting a more complicated mechanism associated with the rNOE at -1.6 ppm in biological membranes.

Reproducible and Bendable SERS Substrates with Tailored Wettability Using Block Copolymers and Anodic Aluminum Oxide Templates.

Surface properties are essential for substrates exhibiting high sensitivity in surface-enhanced Raman scattering (SERS) applications. In this work, novel SERS hybrid substrates using polystyrene-block-poly(methyl methacrylate) and anodic aluminum oxide templates is presented. The hybrid substrates not only possess hierarchical porous nanostructures but also exhibit superhydrophilic surface properties with the water contact angle ≈0°. Such surfaces play an important role in providing uniform enhanced intensities over large areas (relative standard deviation ≈10%); moreover, these substrates are found to be highly sensitive (limit of detection ≈10-12 m for rhodamine 6G (R6G)). The results show that the hybrid SERS substrates can achieve the simultaneous detection of multicomponent mixtures of different target molecules, such as R6G, crystal violet, and methylene blue. Furthermore, the bending experiments show that about 70% of the SERS intensities are maintained after bending from ≈30° to 150°.