Relationship of Metabolic Dysfunction-Associated Steatohepatitis-Related Hepatocellular Carcinoma with Oral and Intestinal Microbiota: A Cross-Sectional Pilot Study.

Background and Objectives: The incidence of metabolic dysfunction-associated steatohepatitis (MASH)-related hepatocellular carcinoma (HCC) is increasing worldwide, alongside the epidemic of obesity and metabolic syndrome. Based on preliminary reports regarding the potential association of HCC and periodontitis, this study aimed to analyze the involvement of periodontal bacteria as well as the oral and intestinal bacterial flora in MASH-related HCC (MASH-HCC). Materials and Methods: Forty-one patients with MASH and nineteen with MASH-HCC participated in the study, completing survey questionnaires, undergoing periodontal examinations, and providing samples of saliva, mouth-rinsed water, feces, and peripheral blood. The oral and fecal microbiome profiles were analyzed by 16S ribosomal RNA sequencing. Bayesian network analysis was used to analyze the causation between various factors, including MASH-HCC, examinations, and bacteria. Results: The genus Fusobacterium had a significantly higher occupancy rate (p = 0.002) in the intestinal microflora of the MASH-HCC group compared to the MASH group. However, Butyricicoccus (p = 0.022) and Roseburia (p < 0.05) had significantly lower occupancy rates. The Bayesian network analysis revealed the absence of periodontal pathogenic bacteria and enteric bacteria affecting HCC. However, HCC directly affected the periodontal bacterial species Porphyromonas gingivalis, Tannerella forsythia, Fusobacterium nucleatum, and Prevotella intermedia in the saliva, as well as the genera Lactobacillus, Roseburia, Fusobacterium, Prevotella, Clostridium, Ruminococcus, Trabulsiella, and SMB53 in the intestine. Furthermore, P. gingivalis in the oral cavity directly affected the genera Lactobacillus and Streptococcus in the intestine. Conclusions: MASH-HCC directly affects periodontal pathogenic and intestinal bacteria, and P. gingivalis may affect the intestinal bacteria associated with gastrointestinal cancer.

EP4-induced mitochondrial localization and cell migration mediated by CALML6 in human oral squamous cell carcinoma.

Lymph node metastasis, primarily caused by the migration of oral squamous cell carcinoma (OSCC) cells, stands as a crucial prognostic marker. We have previously demonstrated that EP4, a subtype of the prostaglandin E2 (PGE2) receptor, orchestrates OSCC cell migration via Ca2+ signaling. The exact mechanisms by which EP4 influences cell migration through Ca2+ signaling, however, is unclear. Our study aims to clarify how EP4 controls OSCC cell migration through this pathway. We find that activating EP4 with an agonist (ONO-AE1-473) increased intracellular Ca2+ levels and the migration of human oral cancer cells (HSC-3), but not human gingival fibroblasts (HGnF). Further RNA sequencing linked EP4 to calmodulin-like protein 6 (CALML6), whose role remains undefined in OSCC. Through protein-protein interaction network analysis, a strong connection is identified between CALML6 and calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2), with EP4 activation also boosting mitochondrial function. Overexpressing EP4 in HSC-3 cells increases experimental lung metastasis in mice, whereas inhibiting CaMKK2 with STO-609 markedly lowers these metastases. This positions CaMKK2 as a potential new target for treating OSCC metastasis. Our findings highlight CALML6 as a pivotal regulator in EP4-driven mitochondrial respiration, affecting cell migration and metastasis via the CaMKK2 pathway.

Diameters of lingual, facial, and maxillary arteries measured according to an objective protocol on 3D computed tomography angiography images.

PURPOSE: Retrograde superselective intra-arterial chemoradiotherapy is a radical treatment for advanced oral cancer. The catheter tip is placed into tumor-feeding arteries-the lingual, facial, or maxillary arteries. The diameter of the tumor-feeding arteries newly bifurcated from the external carotid artery is crucial for determining the requirement of a catheter navigation system. This study aimed to measure the diameter and distribution of the tumor-feeding artery according to an objective protocol using 3D computed tomography angiography images reproducibly. METHODS: Angiographic data of 20 noncatheterized carotid arteriesof 10 randomly selected patients were analyzed. We followed the external carotid artery to the entrance of each feeding artery to determine the center point where the artery diameter was measured. The diameter of the optimum circle measured at the adopted center point was taken as the diameter of each tumor-feeding artery. RESULTS: The diameters (mean ± standard deviation) were 3.5 ± 0.45, 2.9 ± 0.56, and 3.5 ± 0.56 mm for the maxillary, lingual, and facial arteries, respectively. The diameters of the maxillary and facial arteries were similar (p = 0.877), whereas the diameter of the lingual artery was smaller than that of the maxillary and facial arteries (p < 0.001). CONCLUSION: The findings of this study will be beneficial in determining the need of a new catheter navigation system and diameter of catheters to be used in the clinical practice. From the viewpoint of measurement automation and reproducibility, 3DCTA vessel measurement taken according to the proposed protocol was considered to be effective.

Synergistic Enhancement of Protein Recruitment and Retention via Implant Surface Microtopography and Superhydrophilicity in a Computational Fluid Dynamics Model.

The exact mechanisms by which implant surface properties govern osseointegration are incompletely understood. To gain insights into this process, we examined alterations in protein and blood recruitment around screw implants with different surface topographies and wettability using a computational fluid dynamics (CFD) model. Compared with a smooth surface, a microrough implant surface reduced protein infiltration from the outer zone to the implant thread and interface zones by over two-fold. However, the microrough implant surface slowed blood flow in the interface zone by four-fold. As a result, compared with the smooth surface, the microrough surface doubled the protein recruitment/retention index, defined as the mass of proteins present in the area per unit time. Converting implant surfaces from hydrophobic to superhydrophilic increased the mass of protein infiltration 2-3 times and slowed down blood flow by up to two-fold in the implant vicinity for both smooth and microrough surfaces. The protein recruitment/retention index was highest at the implant interface when the implant surface was superhydrophilic and microrough. Thus, this study demonstrates distinct control of the mass and speed of protein and blood flow through implant surface topography, wettability, and their combination, significantly altering the efficiency of protein recruitment. Although microrough surfaces showed both positive and negative impacts on protein recruitment over smooth surfaces, superhydrophilicity was consistently positive regardless of surface topography.

Accuracy and influencing factors of maxillary and mandibular repositioning using pre-bent locking plates: a prospective study.

In-house repositioning methods based on three-dimensional (3D)-printing technology and the use of pre-bent plates has been gaining popularity in orthognathic surgery. However, there remains room for further improvement in methods and investigations on clinical factors that affect accuracy. This single-centre, prospective study included 34 patients and aimed to evaluate the accuracy and factors influencing maxillary and mandibular repositioning using pre-bent locking plates. The plates were manually pre-bent on the 3D-printed models of the planned position, and their hole positions were scanned and reproduced intraoperatively with osteotomy guides. The accuracy of repositioning and plate-hole positioning was calculated in three axes with the set landmarks. The following clinical factors that affect repositioning accuracy were also verified: deviation of the plate-hole positioning, amount of planned movement, and amount of simulated bony interference. The median deviations of the repositioning and hole positioning between the preoperative plan and postoperative results were 0.26 mm and 0.23 mm, respectively, in the maxilla, and 0.69 mm and 0.36 mm, respectively, in the mandible, suggesting that the method was highly accurate, and the repositioning concept based on the plate hole and form matching was more effective in the maxilla. Results of the correlation test suggest that large amounts of bony interference and plate-hole positioning errors in the up/down direction could reduce mandibular repositioning accuracy.

The Effects of a Biomimetic Hybrid Meso- and Nano-Scale Surface Topography on Blood and Protein Recruitment in a Computational Fluid Dynamics Implant Model.

The mechanisms underlying bone-implant integration, or osseointegration, are still incompletely understood, in particular how blood and proteins are recruited to implant surfaces. The objective of this study was to visualize and quantify the flow of blood and the model protein fibrinogen using a computational fluid dynamics (CFD) implant model. Implants with screws were designed with three different surface topographies: (1) amorphous, (2) nano-trabecular, and (3) hybrid meso-spikes and nano-trabeculae. The implant with nano-topography recruited more blood and fibrinogen to the implant interface than the amorphous implant. Implants with hybrid topography further increased recruitment, with particularly efficient recruitment from the thread area to the interface. Blood movement significantly slowed at the implant interface compared with the thread area for all implants. The blood velocity at the interface was 3- and 4-fold lower for the hybrid topography compared with the nano-topography and amorphous surfaces, respectively. Thus, this study for the first time provides insights into how different implant surfaces regulate blood dynamics and the potential advantages of surface texturization in blood and protein recruitment and retention. In particular, co-texturization with a hybrid meso- and nano-topography created the most favorable microenvironment. The established CFD model is simple, low-cost, and expected to be useful for a wide range of studies designing and optimizing implants at the macro and micro levels.