Ferroptosis Holds Novel Promise in Treatment of Cancer Mediated by Non-coding RNAs

Ferroptosis is a newly identified form of regulated cell death that is associated with iron metabolism and oxidative stress. As a physiological mechanism, ferroptosis selectively removes cancer cells by regulating the expression of vital chemical molecules. Current findings on regulation of ferroptosis have largely focused on the function of non-coding RNAs (ncRNAs), especially microRNAs (miRNAs), in mediating ferroptotic cell death, while the sponging effect of circular RNAs (circRNAs) has not been widely studied. In this review, we discuss the molecular regulation of ferroptosis and highlight the value of circRNAs in controlling ferroptosis and carcinogenesis. Herein, we deliberate future role of this emerging form of regulated cell death in cancer therapeutics and predict the progression and prognosis of oncogenesis in future clinical therapy

The role of novel programmed cell death in head and neck squamous cell carcinoma: from mechanisms to potential therapies

Head and neck squamous cell carcinoma (HNSCC) is a common oral cancer with poor prognosis and for which no targeted therapeutic strategies are currently available. Accumulating evidence has demonstrated that programmed cell death (PCD) is essential in the development of HNSCC as a second messenger. PCD can be categorized into numerous different subroutines: in addition to the two well-known types of apoptosis and autophagy, novel forms of programmed cell death (e.g., necroptosis, pyroptosis, ferroptosis, and NETosis) also serve as key alternatives in tumorigenesis. Cancer cells are not able to avoid all types of cell death simultaneously, since different cell death subroutines follow different regulatory pathways. Herein, we summarize the roles of novel programmed cell death in tumorigenesis and present our interpretations of the molecular mechanisms with a view to the development of further potential therapies

Surgical management of Squamous Cell Carcinoma of the lower lip: an experience of 109 cases

Objectives: We are presenting our experience collected from a series of 109 cases with SCC of the lower lip focus - ing on clinical features of patients and surgical approach. Study D esign: We retrospectively analyzed medical records of patients diagnosed with Squamous Cell Carcinoma (SCC) of the lower lip at the Oral and Maxillofacial surgery at Xi'an Jiaotong University during a period between 1999 and 2008. Results: A total of 109 patients with lip cancer were included in the study. When no frozen-section test was per - formed, the neoplasia was removed with a margin of at least 6 mm. Different surgical techniques were used for lip reconstruction after tumor excision. Neck dissection was performed in all patients with clinically palpable lymph nodes. Median follow-up was 38 months. During follow-up, recurrence occurred in 5 patients, 3 patients devel - oped neck metastases, distant metastases developed in 1 patient. Five patients died during observation period. Conclusions: The patient-related and defect-related issues must be taken into consideration during reconstruction for surgical defect. For N0 patients, we recommend wait-and-see policy. Early detection, careful follow-up and prompt neck is essential for the successful treatment

Virtual Planning and 3D printing modeling for mandibular reconstruction with fibula free flap

This study was to evaluate the use of virtual planning and 3D printing modeling in mandibular reconstruction and compare the operation time and surgical outcome of this technique with conventional method. Between 2014 and 2017, 15 patients underwent vascularized fibula flap mandibular reconstruction using virtual planning and 3D printing modeling. Titanium plates were pre-bent using the models and cutting guides were used for osteotomies. 15 patients who underwent mandibular reconstruction using fibula flap without aid of virtual planning and 3D printing models were selected as control group. The operation time was recorded and compared in two groups. Accuracy of reconstruction was measured by superimposing the preoperative image onto the postoperative image of mandible. The selected bony landmark, distance and angle were measured. The mean total operation time and reconstruction time were 1.60±0.37 and 5.54±0.50 hours in computer-assisted group, respectively; These were 2.58±0.45 and 6.54±0.70 hours in conventional group, respectively. Both operation time and reconstruction time were shorter in computer-assisted group. The difference between the preoperative and postoperative intercondylar distances, intergonial angle distances, anteroposterior distances and gonial angles were 2.92±1.15 and 4.48±1.41mm, 2.93±1.19 and 4.79±1.48mm, 4.31±1.24 and 5.61±1.41mm, 3.85±1.68° and 5.88±2.12° in the computer-assisted and conventional group, respectively. The differences between the preoperative and postoperative mandible is smaller in the computer-assisted group. Virtual planning and 3D printing modeling have the potential to increase mandibular reconstruction accuracy and reduce operation time. we believe that this technology for mandibular reconstruction in selected patients will become a used method and improve the quality of reconstruction

Analysis of Three-Dimensional Morphological Differences in the Mandible between Skeletal Class I and Class II with CBCT Fixed-Point Measurement Method

This study was aimed at determining the three-dimensional differences in the mandible morphology between skeletal class I and II patients, at exploring the pathogenic mechanisms and morphological characteristics of skeletal class II, and at providing clinical references. The subjects were assigned to two groups according to the size of ANB angle: skeletal class I (2°<ANB angle<5°) and skeletal class II (5°<ANB angle<8°). After cone-beam computed tomography (CBCT) scanning, 31 landmarks and 25 measurement items were determined by In Vivo Dental 5.1 software (Anatomage, CA) for statistical analysis. The results were as follows: Co-Go, Go-Me, and CdM-CdD in skeletal class II cases were smaller than those in skeletal class I, and GoR-Me-GoL, GoR-Me-CoL, and, Ig-Men were larger than those in skeletal class I cases. In conclusion, there were significant differences in the three-dimensional morphology of the mandible between skeletal class I and class II patients. The vertical growth of the ramus, the horizontal growth of the mandibular body, and the condyle in skeletal class II patients were smaller than those in skeletal class I cases. In skeletal class II, the growth of the anterior part of the mandible in the vertical direction was larger than that in skeletal class I, and the shape of the mandible was more extended

Structure and Function of a C–C Bond Cleaving Oxygenase in Atypical Angucycline Biosynthesis

C–C bond ring cleaving oxygenases represent a unique family of enzymes involved in the B ring cleavage reaction only observed in atypical angucycline biosynthesis. B ring cleavage is the key reaction leading to dramatic divergence in the final structures of atypical angucyclines. Here, we present the crystal structure of AlpJ, the first structure of this family of enzymes. AlpJ has been verified as the enzyme catalyzing C–C bond cleavage in kinamycin biosynthesis. The crystal structure of the AlpJ monomer resembles the dimeric structure of ferredoxin-like proteins. The N- and C-terminal halves of AlpJ are homologous, and both contain a putative hydrophobic substrate binding pocket in the “closed” and “open” conformations, respectively. Structural comparison of AlpJ with ActVA-Orf6 and protein–ligand docking analysis suggest that the residues including Asn60, Trp64, and Trp181 are possibly involved in substrate recognition. Site-directed mutagenesis results supported our hypothesis, as mutation of these residues led to nearly a complete loss of the activity of AlpJ. Structural analysis also revealed that AlpJ possesses an intramolecular domain–domain interface, where the residues His50 and Tyr178 form a hydrogen bond that probably stabilizes the three-dimensional structure of AlpJ. Site-directed mutagenesis showed that the two residues, His50 and Tyr178, were vital for the activity of AlpJ. Our findings shed light on the structure and catalytic mechanism of the AlpJ family of oxygenases, which presumably involves two active sites that might function in a cooperative manner