Interaction of Apoptotic Cells with Macrophages Upregulates COX-2/PGE 2

Recognition of apoptotic cells by macrophages is crucial for resolution of inflammation, immune tolerance, and tissue repair. Cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) and hepatocyte growth factor (HGF) play important roles in the tissue repair process. We investigated the characteristics of macrophage COX-2 and PGE2 expression mediated by apoptotic cells and then determined how macrophages exposed to apoptotic cells in vitro and in vivo orchestrate the interaction between COX-2/PGE2 and HGF signaling pathways. Exposure of RAW 264.7 cells and primary peritoneal macrophages to apoptotic cells resulted in induction of COX-2 and PGE2. The COX-2 inhibitor NS-398 suppressed apoptotic cell-induced PGE2 production. Both NS-398 and COX-2-siRNA, as well as the PGE2 receptor EP2 antagonist, blocked HGF expression in response to apoptotic cells. In addition, the HGF receptor antagonist suppressed increases in COX-2 and PGE2 induction. The in vivo relevance of the interaction between the COX-2/PGE2 and HGF pathways through a positive feedback loop was shown in cultured alveolar macrophages following in vivo exposure of bleomycin-stimulated lungs to apoptotic cells. Our results demonstrate that upregulation of the COX-2/PGE2 and HGF in macrophages following exposure to apoptotic cells represents a mechanism for mediating the anti-inflammatory and antifibrotic consequences of apoptotic cell recognition

Minimum Surgico-Orthopedic Treatment using Computer-Assisted Single-Tooth Osteotomy in an Adolescent Skeletal Class III Patient with Anterior Ankylosed Tooth: A Case Report

Traumatic tooth avulsion can lead to ankylosis, which may interfere with growth of the alveolar bone in a growing patient. The resulting difference in alveolar bone height and position can lead to esthetic problems such as open bite.A growing 13-year-old female patient presented skeletal Class III malocclusion with bone ankylosis of a maxillary anterior tooth. Even after 2 years of orthopedic and orthodontic treatment, little improvement was achieved regarding the positions of the anterior maxillary teeth, or the vertical position of the maxillary right central incisor. Therefore, surgical treatment by single-tooth osteotomy (STO) and corticotomy for the anterior ankylosed tooth were considered and performed using a CAD/CAM surgical guide, based on presurgical computer-based simulation surgery. Orthodontic and orthopedic treatments were completed at 10 months after surgery. The patient showed a favorable course of healing, with no mobility issues or gingival recession 3 years after single-tooth osteotomy and corticotomy surgeries. A favorable outcome was finally achieved by applying orthopedic treatment combined with STO and corticotomy for the anterior ankylosed tooth. Orthodontic treatment with minimally surgical method is recommended in an adolescent patient with skeletal Class III malocclusion and anterior open bite

Non-thermal atmospheric pressure plasma-conditioned root dentin promotes attraction and attachment of primary human dental pulp stem cells in real-time Ex Vivo

This study investigated if non-thermal atmospheric pressure plasma (NTAPP) treatment of root dentin surfaces promotes human dental pulp stem cell (hDPSCs) adhesion. Freshly extracted human single-rooted teeth (n = 36) were decoronated and cut (first vertically, then horizontally) into root dentin slices (3 mm thick). Primary hDPSCs cultures were seeded onto slices randomly assigned to pretreatment groups (n = 9/group): NaOCl (1.5%), EDTA (17%) then NTAPP (Group I); NaOCl then NTAPP (Group II); NaOCl then EDTA (Group III); and NaOCl alone (Group IV). Cell viability and proliferation were measured using MTT assay with log-linear statistical analysis. Cell attachment and spreading morphologies on dentin slices (n = 3/group) were examined through scanning electron microscopy. Early cell adhesion events and subcellular activities were observed in real time by live-cell imaging through holotomographic microscopy. Cell viability and proliferation were significantly higher on NTAPP-treated dentin (p \u3c 0.05), without interactions with EDTA (p \u3e 0.05). The attachment, spreading, extensions and multiple layers of hDPSCs were heightened on NTAPP-treated dentin. Cell adhesion, spreading, and dentinal tubule penetration were hastened on NTAPP-treated dentin surfaces in real-time, with elevated subcellular activities and intracellular lipid droplet formation. NTAPP-treated root dentin surfaces support enhanced cellular responses, potentially promoting pulp-dentin regeneration

A scoping review of music-based interventions for swallowing difficulties: implications for treating older adults with presbyphagia

ObjectivesPresbyphagia refers to age-related changes in the swallowing mechanism (e.g., reduced skeletal muscle strength that decreases bolus control). If left untreated, these changes can lead to dysphagia, which refers to impaired swallowing (e.g., coughing or choking when eating). Given that swallowing difficulties are common among older adults that they make up the fastest growing age group globally, the need for interventions to address presbyphagia is gaining urgency. To begin to address this need, we conducted a scoping review to analyze music therapy research aimed at enhancing swallowing function. The objective was to identify key intervention characteristics and propose clinical implications for treating presbyphagia using music therapy.MethodsThis review followed the methodological frameworks outlined by Arksey and O’Malley and Levac et al. and used the Preferred Reporting Items for Systematic Reviews and Meta-Analysis for Scoping Reviews for analysis and reporting. Four electronic databases (i.e., ProQuest, PubMed, RISS, Web of Science) were searched for quantitative and qualitative studies in English or Korean that used music-based interventions to address swallowing function in older adults. Content analysis was conducted to identify and compare the main features of music interventions for swallowing difficulties among older adults.ResultsTen articles were identified and analyzed. It was found that three core components–respiration, vocalization, and singing–were employed to enhance swallowing function in populations with neurological impairments, dementia, or head and neck cancer. Notably, actions closely linked to swallowing function, such as laryngeal elevation and oral movements, were utilized therapeutically to speak or sing. Based on these characteristics, clinical implications are proposed to address presbyphagia.ConclusionSinging entails a systematic and focused incorporation of stepwise activities that can be used to address swallowing disorders. In this context, critical clinical implications that music therapists should consider when treating individuals with presbyphagia include warmup breathing, vocalizing targeting laryngeal control, and singing targeting oral motor control. This review can contribute to the expansion of music therapy with older adults and the advancement of music therapy techniques

Temporal Interpolation Is All You Need for Dynamic Neural Radiance Fields

Temporal interpolation often plays a crucial role to learn meaningful representations in dynamic scenes. In this paper, we propose a novel method to train spatiotemporal neural radiance fields of dynamic scenes based on temporal interpolation of feature vectors. Two feature interpolation methods are suggested depending on underlying representations, neural networks or grids. In the neural representation, we extract features from space-time inputs via multiple neural network modules and interpolate them based on time frames. The proposed multi-level feature interpolation network effectively captures features of both short-term and long-term time ranges. In the grid representation, space-time features are learned via four-dimensional hash grids, which remarkably reduces training time. The grid representation shows more than 100 times faster training speed than the previous neural-net-based methods while maintaining the rendering quality. Concatenating static and dynamic features and adding a simple smoothness term further improve the performance of our proposed models. Despite the simplicity of the model architectures, our method achieved state-of-the-art performance both in rendering quality for the neural representation and in training speed for the grid representation.Comment: CVPR 2023. Project page: https://sungheonpark.github.io/tempinterpner

Effect of rhBMP-2 applied with a 3D-printed titanium implant on new bone formation in rabbit calvarium

Objective: This study sought to compare the biocompatibility of a three-dimensional (3D)-printed titanium implant with a conventional machined titanium product, as well as the effect of such implant applied with recombinant human Bone Morphogenetic Protein Type 2 (rhBMP-2) for guided bone regeneration. Methodology: Disk-shaped titanium specimens fabricated either by the conventional machining technique or by the 3D-printing technique were compared by MC3T3-E1 cells cytotoxicity assay. New bone formation was evaluated using a rapid prototype titanium cap applied to the calvaria of 10 rabbits, which were divided into two groups: one including an atelopeptide collagen plug on one side of the cap (group I) and the other including a plug with rhBMP-2 on the other side (group II). At six and 12 weeks after euthanasia, rabbits calvaria underwent morphometric analysis through radiological and histological examination. Results: Through the cytotoxicity assay, we identified a significantly higher number of MC3T3-E1 cells in the 3D-printed specimen when compared to the machined specimen after 48 hours of culture. Moreover, morphometric analysis indicated significantly greater bone formation at week 12 on the side where rhBMP-2 was applied when evaluating the upper portion immediately below the ca p. Conclusion: The results suggest that 3D-printed titanium implant applied with rhBMP-2 enables new bone formation

Association of serum adipocytokine levels with cardiac autonomic neuropathy in type 2 diabetic patients

<p>Abstract</p> <p>Background</p> <p>Cardiac autonomic neuropathy (CAN) is a common complication of diabetes associated with poor prognosis. In addition, the autonomic imbalance is associated with cardiovascular disease (CVD) in diabetes. It is thought that adipocytokines contribute to the increased risk of vascular complications in patients with type 2 diabetes mellitus (T2DM). However, literature data on the association between CAN with adipocytokines such as leptin, tumor necrosis factor-alpha (TNF-alpha), adiponectin in subjects with T2DM is limited.</p> <p>Therefore, in the present study, we examined the relationship between fasting serum leptin, TNF- alpha and adiponectin and CAN in Korean T2DM patients.</p> <p>Methods</p> <p>A total of 142 T2DM patients (94 males, 48 females) were recruited. CAN was assessed by the five tests according to the Ewing's protocol and the time and frequency domain of the heart rate variability (HRV) was evaluated. Serum TNF-alpha and adiponectin levels were measured using enzyme-linked immunosorbent assay and serum leptin levels were measured using radioimmunoassay.</p> <p>Results</p> <p>Although, the mean levels of leptin, TNF-alpha and adiponectin were not significantly different between the groups with and without CAN, the levels of leptin and adiponectin had a tendency to increase as the score of CAN increased (p = 0.05, p = 0.036). Serum leptin levels demonstrated a negative correlation with low frequency (LF) in the upright position (p = 0.037). Regarding TNF-alpha, a significant negative correlation was observed with SDNN and RMSSD in the upright position (p = 0.023, p = 0.019). Adiponectin levels were not related to any HRV parameters. Multivariate logistic regression analysis demonstrated that the odds of CAN increased with a longer duration of diabetes (1.25, [1.07-1.47]) and higher homeostatic model of assessment-insulin resistance (HOMA-IR) (5.47, [1.8-16.5]). The relative risks for the presence of CAN were 14.1 and 51.6 for the adiponectin 2^nd, 3^rdtertiles when compared with first tertile (p-value for trend = 0.022).</p> <p>Conclusions</p> <p>In the present study, the higher serum adiponectin levels and HOMA-IR were associated with an increased risk for the presence of CAN. Also, the CAN score correlated with the serum adiponectin. Serum adipocytokines such as leptin and TNF-alpha were significantly correlated with parameters of HRV, representative markers of CAN. Future prospective studies with larger number of patients are required to establish a direct relationship between plasma adipocytokine concentrations and the development or severity of CAN.</p

Unleashing the full potential of Hsp90 inhibitors as cancer therapeutics through simultaneous inactivation of Hsp90, Grp94, and TRAP1

Cancer therapeutics: Extending a drug&apos;s reach A new drug that blocks heat shock proteins (HSPs), helper proteins that are co-opted by cancer cells to promote tumor growth, shows promise for cancer treatment. Several drugs have targeted HSPs, since cancer cells are known to hijack these helper proteins to shield themselves from destruction by the body. However, the drugs have had limited success. Hye-Kyung Park and Byoung Heon Kang at Ulsan National Institutes of Science and Technology in South Korea and coworkers noticed that the drugs were not absorbed into mitochondria, a key cellular compartment, and HSPs in this compartment were therefore not being blocked. They identified a new HSP inhibitor that can reach every cellular compartment and inhibit all HSPs. Testing in mice showed that this inhibitor effectively triggered death of tumor cells, and therefore shows promise for anti-cancer therapy. The Hsp90 family proteins Hsp90, Grp94, and TRAP1 are present in the cell cytoplasm, endoplasmic reticulum, and mitochondria, respectively; all play important roles in tumorigenesis by regulating protein homeostasis in response to stress. Thus, simultaneous inhibition of all Hsp90 paralogs is a reasonable strategy for cancer therapy. However, since the existing pan-Hsp90 inhibitor does not accumulate in mitochondria, the potential anticancer activity of pan-Hsp90 inhibition has not yet been fully examined in vivo. Analysis of The Cancer Genome Atlas database revealed that all Hsp90 paralogs were upregulated in prostate cancer. Inactivation of all Hsp90 paralogs induced mitochondrial dysfunction, increased cytosolic calcium, and activated calcineurin. Active calcineurin blocked prosurvival heat shock responses upon Hsp90 inhibition by preventing nuclear translocation of HSF1. The purine scaffold derivative DN401 inhibited all Hsp90 paralogs simultaneously and showed stronger anticancer activity than other Hsp90 inhibitors. Pan-Hsp90 inhibition increased cytotoxicity and suppressed mechanisms that protect cancer cells, suggesting that it is a feasible strategy for the development of potent anticancer drugs. The mitochondria-permeable drug DN401 is a newly identified in vivo pan-Hsp90 inhibitor with potent anticancer activity

Brucellosis among ruminants in some districts of Bangladesh using four conventional serological assays

Brucellosis causes a great economic loss to the livestock industries through abortion, infertility, birth of weak and dead offspring, increased calving interval and reduction of milk yield and it is endemic in Bangladesh. The present study was performed to know the seroprevalence of brucellosis for 1000 ruminants (135 Buffaloes, 465 cattle, 230 goats and 170 sheep) in five different districts of Bangladesh by four conventional serological tests such as: Rose Bengal Plate Test (RBT), tube agglutination test (TAT), competitive enzyme-linked immunosorbent assay (C-ELISA), and Fluorescent polarization assay (FPA). Sheep has the highest prevalence (8.24%) of brucellosis. The seroprevalence of brucellosis was significantly higher in animals with previous abortion record in case of buffaloes, cattle, goats and sheep than that with no abortion record. C-ELISA can be the most suitable choice for extensive use in many kinds of livestocks and accurate estimation of Brucella antibodies in ruminants in Bangladesh