TRIM21-mediated ubiquitylation of TAT suppresses liver metastasis in gallbladder cancer.

Liver metastasis is common in patients with gallbladder cancer (GBC), imposing a significant challenge in clinical management and serving as a poor prognostic indicator. However, the mechanisms underlying liver metastasis remain largely unknown. Here, we report a crucial role of tyrosine aminotransferase (TAT) in liver metastasis of GBC. TAT is frequently up-regulated in GBC tissues. Increased TAT expression is associated with frequent liver metastasis and poor prognosis of GBC patients. Overexpression of TAT promotes GBC cell migration and invasion in vitro, as well as liver metastasis in vivo. TAT knockdown has the opposite effects. Intriguingly, TAT promotes liver metastasis of GBC by potentiating cardiolipin-dependent mitophagy. Mechanistically, TAT directly binds to cardiolipin and leads to cardiolipin externalization and subsequent mitophagy. Moreover, TRIM21 (Tripartite Motif Containing 21), an E3 ubiquitin ligase, interacts with TAT. The histine residues 336 and 338 at TRIM21 are essential for this binding. TRIM21 preferentially adds the lysine 63 (K63)-linked ubiquitin chains on TAT principally at K136. TRIM21-mediated TAT ubiquitination impairs its dimerization and mitochondrial location, subsequently inhibiting tumor invasion and migration of GBC cells. Therefore, our study identifies TAT as a novel driver of GBC liver metastasis, emphasizing its potential as a therapeutic target.

Specific tissue engineering for temporomandibular joint disc perforation.

BACKGROUND: The temporomandibular joint (TMJ) disc is a critical fibrocartilaginous structure with limited regenerative capacity in the oral system. Perforation of the TMJ disc can lead to osteoarthritis and ankylosis of the TMJ because of the lack of disc protection. Clinical treatments for TMJ disc perforation, such as discectomy, hyaluronic acid injection, endoscopic surgery and high position arthroplasty of TMJ, are questionable with regard to long-term outcomes, and only three fourths of TMJ disc perforations are repairable by surgery, even in the short-term. Tissue engineering offers the potential for cure of repairable TMJ disc perforations and regeneration of unrepairable ones. OBJECTIVES: This review discusses the classification of TMJ disc perforation and defines typical TMJ disc perforation. Advancements in the engineering-based repair of TMJ disc perforation by stem cell therapy, construction of a disc-like scaffold and functionalization by offering bioactive stimuli are also summarized in the review, and the barriers developing engineering technologies need to overcome to be popularized are discussed.

Application of Fluorescence In Situ Hybridization (FISH) in Oral Microbial Detection.

Varieties of microorganisms reside in the oral cavity contributing to the occurrence and development of microbes associated with oral diseases; however, the distribution and in situ abundance in the biofilm are still unclear. In order to promote the understanding of the ecosystem of oral microbiota and the diagnosis of oral diseases, it is necessary to monitor and compare the oral microorganisms from different niches of the oral cavity in situ. The fluorescence in situ hybridization (FISH) has proven to be a powerful tool for representing the status of oral microorganisms in the oral cavity. FISH is one of the most routinely used cytochemical techniques for genetic detection, identification, and localization by a fluorescently labeled nucleic acid probe, which can hybridize with targeted nucleic acid sequences. It has the advantages of rapidity, safety, high sensitivity, and specificity. FISH allows the identification and quantification of different oral microorganisms simultaneously. It can also visualize microorganisms by combining with other molecular biology technologies to represent the distribution of each microbial community in the oral biofilm. In this review, we summarized and discussed the development of FISH technology and the application of FISH in oral disease diagnosis and oral ecosystem research, highlighted its advantages in oral microbiology, listed the existing problems, and provided suggestions for future development..

Successful conversion surgery for locally advanced gallbladder cancer after gemcitabine and nab-paclitaxel chemotherapy.

Objective: Gallbladder cancer (GBC) is highly malignant and is often diagnosed at the advanced stage. Lack of opportunity to surgery results in an unsatisfactory outcome. This pilot study employed gemcitabine combined with nab-paclitaxel (AG) as a conversion therapeutic measure for locally advanced GBC and successfully achieved conversion surgery in three initially unresectable GBC patients. We will introduce our experience on improving the outcome of this dismal disease. Methods: Radiology and nuclear medicine imaging were performed in each patient, and resectability was evaluated by joint consultation of our multi-disciplinary team (MDT). Patients evaluated as unresectable were treated with the AG regimen and re-evaluated for treatment response. When complete or partial response is achieved, MDT opinion would be required to assess the possibility of performing conversion surgery with R0 resection. Results: Three GBC patients who were initially evaluated as unresectable successfully underwent R0 resection after conversion therapy with the AG regimen. The first case was a recurrent GBC patient evaluated as locally advanced and eventually achieved pathological complete response. The second case was a GBC patient who underwent R1 resection with residual lesions in the gallbladder bed and isolated No. 16 lymph node metastasis and who had a pathologically complete response after treatment. The third case had multiple but resectable liver metastases; both objective response and partial pathologic response were achieved. None of the patients experienced serious treatment-related adverse events. All cases revealed no evidence of recurrence or metastasis after a median follow-up of 12 months. Conclusions: Conversion therapy shows a favorable efficacy in those unresectable GBC patients. Gemcitabine plus nab-paclitaxel has the potential to be used as a preoperative treatment option for GBC patients at the advanced stage. To further explore the efficacy of AG on conversion therapy for GBC patients, a prospective clinical trial has been registered (ChiCTR2200055698).