Cell fusion between tumor cells and macrophages promotes the metastasis of OSCC patient through the activation of the chemokine signaling pathway.

BACKGROUND: Tumor metastasis is responsible for the high mortality rate of patients with oral squamous cell carcinoma (OSCC). Although many hypotheses have been proposed to elucidate the mechanism of tumor metastasis, the origin of the metastatic tumor cells remains unclear. In this study, we explored the role of cell fusion in the formation of OSCC metastatic tumor cells. METHODS: Murine OSCC tumor cells and macrophages were fused in vitro, and the cell proliferation, migration, and phagocytosis abilities of hybrid cells and parental cells were compared. Subsequently, we compared the transcriptome differences between hybrid and parental cells. RESULTS: Murine OSCC tumor cells and macrophages were successfully fused in vitro. The cytological and molecular experimental results revealed that OSCC tumor cells obtained a migration-related phenotype after fusion with macrophages, and the migration ability of hybrid cells was related to the activation of the "chemokine signal pathway". CONCLUSION: After fusion with macrophages, the chemokine signaling pathway in OSCC tumor cells was activated, leading to metastasis.

Changes in condylar position and morphology after mandibular reconstruction by vascularized fibular free flap with condyle preservation.

OBJECTS: Changes in condylar position and morphology after mandibular reconstruction are important to aesthetic and functional rehabilitation. We evaluated changes in condylar position and morphology at different stages after mandibular reconstruction using vascularized fibular free flap with condyle preservation. MATERIALS AND METHODS: A total of 23 patients who underwent mandibular reconstruction with fibular flap were included in this retrospective study. CT data of all patients were recorded before surgery (T0), 7 to 14 days after surgery (T1), and at least 6 months after surgery (T2). Five parameters describing the condylar position and 4 parameters describing the morphology were measured in sagittal and coronal views of CT images. The association between clinical characteristics and changes in condylar position and morphology was analyzed. A finite element model was established to investigate the stress distribution and to predict the spatial movement tendency of the condyle after reconstruction surgery. RESULTS: The condylar position changed over time after mandibular reconstruction. The ipsilateral condyles moved inferiorly after surgery (T0 to T1) and continually move anteriorly, inferiorly, and laterally during long-term follow-up (T1 to T2). Contrary changes were noted in the contralateral condyles with no statistical significance. No morphological changes were detected. The relationship between clinical characteristics and changes in condylar position and morphology was not statistically significant. A consistent result was observed in the finite element analysis. CONCLUSION: Condylar positions showed obvious changes over time after mandibular reconstruction with condylar preservation. Nevertheless, further studies should be conducted to evaluate the clinical function outcomes and condylar position. CLINICAL RELEVANCE: These findings can form the basis for the evaluation of short-term and long-term changes in condylar position and morphology among patients who have previously undergone mandibular reconstruction by FFF with condyle preservation.

Recent Advance of Intelligent Packaging Aided by Artificial Intelligence for Monitoring Food Freshness.

Food safety is a pressing concern for human society, as it directly impacts people's lives, while food freshness serves as one of the most crucial indicators in ensuring food safety. There exist diverse techniques for monitoring food freshness, among which intelligent packaging based on artificial intelligence technology boasts the advantages of low cost, high efficiency, fast speed and wide applicability; however, it is currently underutilized. By analyzing the current research status of intelligent packaging both domestically and internationally, this paper provides a clear classification of intelligent packaging technology. Additionally, it outlines the advantages and disadvantages of using intelligent packaging technology for food freshness detection methods, while summarizing the latest research progress in applying artificial intelligence-based technologies to food freshness detection through intelligent packaging. Finally, the author points out the limitations of the current research, and anticipates future developments in artificial intelligence technology for assisting freshness detection in intelligent packaging. This will provide valuable insights for the future development of intelligent packaging in the field of food freshness detection.

Preparation of pH-Responsive Films from Polyvinyl Alcohol/Agar Containing Cochineal for Monitoring the Freshness of Pork.

This study reported the production of pH-responsive films based on 8 wt% polyvinyl alcohol solution/0.2 wt% agar solution incorporated with cochineal-loaded starch particles (CSN) (2, 4, 6 and 8 wt% on agar basis) by a casting process. Results revealed that CSN presented obvious color changes over the pH range of 2-12. FTIR, XRD spectra and SEM micrographs presented that the incorporation of CSN formed new hydrogen bonds with a matrix and a tighter network structure. A certain improvement was observed in the color stability, swelling index and functional properties (antimicrobial and antioxidant activities) but water solubility, water vapor permeability and water contact angle of the pH-responsive films were decreased by the addition of CSN. The release of cochineal was a rate-limiting step following the Korsmeyer-Peppas model. The agar/polyvinyl alcohol film containing 6% CSN (PVA/GG-6) exhibited the best sensitivity for ammonia detection and its limit of detection was 35.4 ppm (part per million) for ammonia. The application trials showed that the PVA/GG-6 film presented different color changes for pork freshness. Hence, these pH-responsive films can be used as potential packaging materials for tracking the freshness of protein-rich fresh food in a non-destructive way.

The feasibility of discriminating BRONJ lesion bone with Raman spectroscopy.

Background: With the frequent use of Bisphosphonates (BPs), the morbidity of BP-related osteonecrosis of the jaw (BRONJ) is also increasing. However, the prevention and treatment of BRONJ is faced with enormous challenges. This study aimed to illuminate the influence of BP administration in the rat mandible and explore the feasibility of discriminating BRONJ lesion bone with Raman spectroscopy. Materials and methods: First, we explored the time- and mode-dependent effects of BP administration on the rat mandible with Raman spectroscopy. Second, the BRONJ rat model was constructed, and the lesion and healthy bone components were analyzed using Raman spectroscopy. Results: When only BPs were administered, no rats showed BRONJ symptoms, and no difference could be found in the Raman spectra. However, when combined with local surgery, six (6/8) rats showed BRONJ symptoms. The Raman spectra also showed a significant difference between the lesion and healthy bone. Conclusion: In the progression of BRONJ, BPs and local stimulation play an essential role. Both BPs administration and local stimulation need to be controlled to prevent BRONJ. Moreover, BRONJ lesion bone in rats could be discriminated with Raman spectroscopy. This novel method would become a complement in the treatment of BRONJ in the future.

Novel colorimetric films based on polyvinyl alcohol/sodium carboxymethyl cellulose doped with anthocyanins and betacyanins to monitor pork freshness.

A novel colorimetric film was developed from polyvinyl alcohol/sodium carboxymethyl cellulose (PVA/CMC-Na, CPA) incorporated with anthocyanins (AHO) or betacyanins (BTA) or AHO and BTA mixtures (in the mass ratios of 2:2, 3:1, 1:3) for intelligent packaging. Fourier transform infrared (FTIR) and scanning electron microscope (SEM) illustrated that AHO/BTA were immobilized into CPA network and improved compatibility of PVA and CMC-Na. The incorporation of AHO/BTA increased the tensile strength (TS), elongation at break (EAB), thickness and water solubility (WS) of the sample but decreased the crystallinity and swelling index (SI) of the sample. Furthermore, the colorimetric films presented antioxidant activity besides antibacterial activity against Escherichia coli and Staphylococcus aureus. The colorimetric film incorporated with AHO and BTA at a mass ratio of 3:1 indicated different colors to represent the freshness of pork. The novel colorimetric film possesses great potential in intelligent packaging for monitoring the real-time freshness of pork products.

Recent Advances in pH-Responsive Freshness Indicators Using Natural Food Colorants to Monitor Food Freshness.

Recently, due to the enhancement in consumer awareness of food safety, considerable attention has been paid to intelligent packaging that displays the quality status of food through color changes. Natural food colorants show useful functionalities (antibacterial and antioxidant activities) and obvious color changes due to their structural changes in different acid and alkali environments, which could be applied to detect these acid and alkali environments, especially in the preparation of intelligent packaging. This review introduces the latest research on the progress of pH-responsive freshness indicators based on natural food colorants and biodegradable polymers for monitoring packaged food quality. Additionally, the current methods of detecting food freshness, the preparation methods for pH-responsive freshness indicators, and their applications for detecting the freshness of perishable food are highlighted. Subsequently, this review addresses the challenges and prospects of pH-responsive freshness indicators in food packaging, to assist in promoting their commercial application.

Accurately Locating Metastatic Foci in Lymph Nodes With Lugol's Iodine-Enhanced Micro-CT Imaging.

BACKGROUND: Accurate evaluation of lymph node (LN) status is the key factor to determine the treatment and evaluate prognosis for patients with cancer. However, traditional pathological examination resulted in a 30% false-negative rate of detection of metastases in LNs. This study aimed to utilize Lugol's iodine (I2-IK)-enhanced micro-CT imaging to reveal the 3-dimensional structure of regional LNs and decrease the false-negative rate in pathological examination. METHODS: To explore the feasibility of I2-IK-enhanced micro-CT imaging in locating metastatic lesion in LNs, nonmetastatic and metastatic LNs from mice were used to mimic the imaging process. Then, the LNs from oral squamous cell carcinoma (OSCC) patients were applied to verify the value of I2-IK-enhanced micro-CT imaging in revealing LN structure and locating metastatic lesions in LNs. The glycogen content in nonmetastatic and metastatic LNs was further detected by the use of a glycogen assay kit and periodic acid-Schiff (PAS) staining to explain the imaging differences between them. RESULTS: In nude mice, 0.5% I2-IK staining for 4 h was the best parameter for normal LN. The metastatic foci in metastatic LNs were also clearly outlined in this condition. For nonmetastatic LNs from patients with OSCC, 1% I2-IK staining for 12 h was the best parameter. However, due to the increased volume of metastatic LNs, the image effect of 3% I2-IK staining for 12 h was superior to 1% I2-IK staining [tumor background ratio (TBR), 3% vs. 1%, 1.89 ± 0.10 vs. 1.27 ± 0.07, p < 0.001]. Compared with subsequent pathological sections, we found the CT intensity of metastatic foci in LNs and muscle tissues was significantly higher than in nonmetastatic regions. Meanwhile, the glycogen content of metastatic foci in LNs detected was also significantly higher than in nonmetastatic region. CONCLUSIONS: I2-IK-enhanced micro-CT imaging could identify the spatial location of metastatic foci in LNs. This will be an effective method to assist in decreasing the LN false-negative rate for cancer pathology.

Integrated analysis of single-cell RNA-seq and bulk RNA-seq reveals distinct cancer-associated fibroblasts in head and neck squamous cell carcinoma.

BACKGROUND: The heterogeneity of cancer-associated fibroblasts (CAFs) in head and neck squamous cell carcinoma (HNSCC) has been widely acknowledged, but has not yet been elucidated. The potential roles and clinical relevance of CAFs subclusters in HNSCC progression remain obscure. METHODS: In this study, we combined single-cell and bulk tissue transcriptome profiles of HNSCC with clinical data from The Cancer Genome Atlas (TCGA). The Seurat package was used to perform single-cell RNA-seq analysis to distinguish distinct CAFs subtypes. Prognostic relevance of several CAFs markers was assessed and functional analysis was also performed. RESULTS: We identified eight CAFs subclusters; of these, seven showed enhanced expression levels in HNSCC tumor tissues compared to normal tissue, and three (clusters 0, 3, and 4) were associated with poorer overall survival. Further functional analysis revealed that cluster 0 was characterized by myofibroblasts with high alpha smooth muscle actin (aSMA) expression and enrichment in smooth muscle contraction. The cluster 3 exhibited expression of extracellular matrix (ECM)-related genes and was enriched in epithelial-mesenchymal transition (EMT)-related gene sets. Cluster 4 expressed high levels of the major histocompatibility complex (MHC) class II family, which was characterized as antigen-presenting CAFs. CONCLUSIONS: We determined CAFs heterogeneity in HNSCC. 8 CAFs subclusters were recognized and 3 of which were prognosis related. The 3 CAFs subclusters showed distinct phenotypes enriched in myofibroblast function, ECM remodeling and antigen-presenting function respectively.

Sentinel lymph node biopsy in oral cavity cancer using indocyanine green: A systematic review and meta-analysis.

This meta-analysis was conducted to evaluate the value of indocyanine green (ICG) in guiding sentinel lymph node biopsy (SLNB) for patients with oral cavity cancer. An electronic database search (PubMed, MEDLINE, Cochrane Library, Embase, and Web of Science) was performed from their inception to June 2020 to retrieve clinical studies of ICG applied to SLNB for oral cavity cancer. Data were extracted from 14 relevant articles (226 patients), and 9 studies (134 patients) were finally included in the meta-analysis according to the inclusion and exclusion criteria. The pooled sentinel lymph node (SLN) sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 88.0% (95% confidence interval [CI], 74.0-96.0), 64.0% (95% CI, 61.0-66.0), 2.45 (95% CI, 1.31-4.60), 0.40 (95% CI, 0.17-0.90), and 7.30 (95% CI, 1.74-30.68), respectively. The area under the summary receiver operating characteristic curve was 0.8805. In conclusion, ICG applied to SLNB can effectively predict the status of regional lymph nodes in oral cavity cancer.

A thermally activated delayed fluorescence photosensitizer for photodynamic therapy of oral squamous cell carcinoma under low laser intensity.

In this report, a new thermally activated delayed fluorescence (TADF) molecule [2-(4-triphenylvinyl-phenyl)-anthraquinone (TPE-AQ)] was synthesized. This nanomaterial has satisfactory photostability. Through In vitro analysis, it was found that these TADF nanoparticles (NPs) targeted lysosomes in oral cancer cells. ROS were released under irradiation with a 450-nm laser, and the growth of xenograft tumors in mouse models was inhibited in vivo. More interestingly, radiation exposure caused little damage to normal tissues due to the low irradiation intensity (mA) used in the photodynamic therapy (PDT) treatment of oral cancer. Therefore, these TADF NPs provide new possibilities for the development of new PDT drugs for biomedical applications. In future work, possible functional modifications of TADF NPs for increased potency in clinical applications will be addressed.

Accuracy of cone-beam computed tomography for the evaluation of mandible invasion by oral squamous cell carcinoma.

BACKGROUND: For patients with oral squamous cell carcinoma (OSCC), accurate evaluation of mandible invasion and resection with appropriate boundaries are important for preserving the structure and function of the mandible and preventing local recurrence. Although cone-beam computed tomography (CBCT), which has high spatial resolution, is now widely used in the diagnosis of oral and maxillofacial bone lesions, no studies have systematically evaluated the accuracy of CBCT for evaluating the presence of bone invasion, the boundaries of bone invasion and the presence of nerve invasion. Therefore, this study aimed to systemically explore the accuracy of CBCT in the preoperative assessment of mandibular invasion by OSCC. METHODS: Thirty mandibular specimens from OSCC patients were collected in this study. The samples were marked and subjected to CBCT examination. Hematoxylin-eosin staining was used for histopathological assessment sed as the gold standard. The evaluation included the presence of bone invasion, the boundaries of bone invasion and the presence of nerve invasion. The CBCT and histopathological boundaries of bone invasion were delineated and merged to compare and calculate the deviation of CBCT in boundary evaluation. RESULTS: The accuracy of CBCT in evaluating the presence of mandible invasion was 100%, and the accuracy of CBCT in evaluating the presence of nerve invasion was 69.2%. A mean deviation of 2.97 mm was found for assessment of the boundary of bone invasion using CBCT compared with the histopathological standard. The interexaminer agreement and intraexaminer agreement were perfect for the detection of bone invasion and nerve invasion (κ > 0.8). The intraclass correlation coefficient was 0.923 for the consistency test of boundary delineation on CBCT images. CONCLUSION: CBCT is quite reliable in determining the presence or absence of mandible invasion but not as reliable for nerve invasion. The deviation in bone invasion boundary estimation should be considered in osteotomy for OSCC.

The Diagnostic Accuracy of Liquid Exosomal miRNAs for Cancer Detection: a Meta-Analysis.

BACKGROUND: Early diagnosis of cancer is related to a good prognosis. Noninvasive methods of body fluid diagnosis are receiving more and more attention. Many studies have shown that exosomal miRNAs in body fluids may be potential biomarkers. Therefore, we conducted a meta-analysis to assess the overall diagnostic value of liquid exosomal miRNAs for cancer. METHODS: Relevant research was retrieved from multiple electronic databases. The research quality was evaluated based on the QUADAS-2 scale in Review Manager 5.3. Diagnostic value was evaluated by data analysis using Stata 16.0, and Meta-DiSc 1.4. RESULTS: The meta-analysis included 23 articles and 79 research units. The pooled sensitivity was 0.74, specificity was 0.78, the diagnostic likelihood ratio positive was 3.55, the diagnostic likelihood ratio negative was 0.29, diagnostic OR was 14.26, and area under the curve was 0.8621. These results provide evidence for liquid exosomal miRNAs as potential biomarkers. CONCLUSIONS: Liquid exosomal miRNAs are potential biomarkers for cancer diagnosis. In particular, diagnosis based on multiple miRNAs is more valuable than a single miRNA.

Biopsy pattern of invasion type to determine the surgical approach in early-stage oral squamous cell carcinoma.

Depth of invasion (DOI) and pattern of invasion (POI) indicate tumor invasiveness of oral squamous cell carcinoma (OSCC). However, preoperative DOI evaluation is challenging, and the correlations between DOI and POI are unknown. We aimed to assess DOI and worst pattern of invasion (WPOI) in early-stage OSCC, and evaluate the preoperative predictive ability of biopsy pattern of invasion (BPOI) for WPOI and DOI. This retrospective study included n = 444 OSCC patients with pT1-2N0M0. The prognostic value of DOI, WPOI, and BPOI and the predictive prognostic option for WPOI and DOI by BPOI were assessed. WPOI (1-3 vs 4-5), but not BPOI, predicted the lowest survival rate and highest DOI. To evaluate the difference between WPOI and BPOI, we conducted a POI type-matching analysis of patients with BPOI1-4 and WPOI1-5. Based on each WPOI type, the false-prediction rates (FPR) of BPOI types 1 (n = 23), 2 (n = 89), 3 (n = 252), and 4 (n = 80) were 52.17%, 52.81%, 36.90%, and 0%, respectively. BPOI4 perfectly predict WPOI 4-5. As the false-predicted BPOI 1-2 was almost WPOI2-3 (79.7%), regardless of the existed FPR, patients with BPOI1-2 have longer survival and lower DOI than those with BPOI 4. However, this phenomenon was not observed in BPOI3, because all false-predicted BPOI3 were WPOI4-5 with a high DOI. We provide an alternative predictive prognostic option for WPOI and DOI by evaluating BPOI during OSCC surgical planning, with the recommendation of conservative treatment in patients with BPOI 1-2.

Thymoquinone loaded calcium alginate and polyvinyl alcohol carrier inhibits the 7,12-dimethylbenz[a]anthracene-induced hamster oral cancer via the down-regulation of PI3K/AKT/mTOR signaling pathways.

Oral cancer is a multifactorial cancer that affects millions of peoples worldwide. The current exploration aimed to evaluate the mechanisms that thymoquinone nanoencapsulated carrier and its effects on 7,12-Dimethylbenz[a]anthracene (DMBA) stimulated hamster buccal pouch cancer in Syrian hamster model. Nanocarrier was characterized by SEM, TEM, FTIR analysis. The incidence of tumor, and biochemicals makers was studied through standard methods. The mRNA expression level of inflammatory markers NF-κBp50, NF-κBp65, and PI3K/AKT/mTOR markers in the buccal tissues of control and experimental animals were investigated through RT-PCR analysis. In thymoquinone (TQ) loaded calcium alginate and polyvinyl alcohol carrier (TQ/Ca-alg-PVA) no squamous cell carcinogenesis developed and others moderate dysplasia revealed differentiated form of hyperplasia and keratosis. In biochemical analyses with DMBA + TQ/Ca-alg-PVA (20 mg/kg bw) orally administered hamsters showed restored the antioxidants, detoxification, xenobiotic metabolising enzymes in DMBA induced plasma and oral tissues of hamsters. Further, mRNA expression level of NF-κBp50/p65 and PI3K/AKT/mTOR were upregulated in the DMBA alone painted hamster. In contrast, these expressions were down regulated in orally TQ/Ca-alg-PVA treated experimental animals. This ability more eligible to deregulate the inflammatory and PI3K/AKT/mTOR signaling pathway that proved it suppresses anti-invasion/metastasis activity during hamster buccal pouch carcinogenesis. From this study, we recommended that TQ/Ca-alg-PVA has documented as effective chemopreventive agents, in further many molecular machineries need to study.

Sentinel lymph node biopsy in oral cavity cancer using indocyanine green: A systematic review and meta-analysis

This meta-analysis was conducted to evaluate the value of indocyanine green (ICG) in guiding sentinel lymph node biopsy (SLNB) for patients with oral cavity cancer. An electronic database search (PubMed, MEDLINE, Cochrane Library, Embase, and Web of Science) was performed from their inception to June 2020 to retrieve clinical studies of ICG applied to SLNB for oral cavity cancer. Data were extracted from 14 relevant articles (226 patients), and 9 studies (134 patients) were finally included in the meta-analysis according to the inclusion and exclusion criteria. The pooled sentinel lymph node (SLN) sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 88.0% (95% confidence interval [CI], 74.0-96.0), 64.0% (95% CI, 61.0-66.0), 2.45 (95% CI, 1.31-4.60), 0.40 (95% CI, 0.17-0.90), and 7.30 (95% CI, 1.74-30.68), respectively. The area under the summary receiver operating characteristic curve was 0.8805. In conclusion, ICG applied to SLNB can effectively predict the status of regional lymph nodes in oral cavity cancer.

A HPV16-related prognostic indicator for head and neck squamous cell carcinoma.

BACKGROUND: The human papillomavirus (HPV) is emerging as an important risk factor in head and neck squamous cell carcinoma (HNSCC) patients. This has been observed particularly in the case of HPV16. The HPV16+ HNSCC subtype has distinct pathological, clinical, molecular, and prognostic characteristics. This study aimed to identify potential microRNAs (miRNAs) and their roles in HPV16+ HNSCC progression. METHOD: miRNA, mRNA and the clinical data of 519 HNSCC and 44 HNSCC-negative samples were obtained from The Cancer Genome Atlas (TCGA) database. Differentially expressed miRNAs (DEMs) in HPV16-related HNSCC tissues with prognostic value were selected. DEM levels were assessed based on clinicopathological parameters and overall survival (OS). Target genes were also predicted and functional analysis based on Gene Set Enrichment Analysis (GSEA) were then performed. RESULTS: In HPV16+ HNSCC tissues, miR-99a-3p and miR-4746-5p were significantly upregulated. In contrast, miR-411-5p was shown to be downregulated. miR-99a-3phighmiR-411-5plowmiR-4746-5phigh expression could estimate improved OS and low frequent perineural invasion (PNI). Predicted target genes were enriched in cell growth, neuroepithelial cell differentiation, MAPK and FoxO signaling pathways. Epithelial mesenchymal transition (EMT) gene set and invasion related genes were downregulated in miR-99a-3phighmiR-411-5plowmiR-4746-5phigh HNSCC patients. CONCLUSION: miR-99a-3p, miR-411-5p and miR-4746-5p might participate in HPV16+ HNSCC progression through EMT related pathways and affect prognosis.

Functional blockade of cancer-associated fibroblasts with ultrafine gold nanomaterials causes an unprecedented bystander antitumoral effect.

Cancer-associated fibroblasts (CAFs) play a critical role in the onset and progression of malignancies, such as oral squamous cell carcinoma (OSCC), making CAFs a promising druggable target. In this study, gold nanoparticles (GNPs) exhibited unprecedented size dependent anti-CAF potential, wherein the smallest GNPs outperformed their larger counterparts. Specifically, a subset of proteins and cytokines that is responsible for the invasive outgrowth of OSCC cells was found to decrease post exposure of OSCC patient-derived CAFs to GNPs. Moreover, the administration of GNPs (3 nm in diameter) could effectively abrogate the growth of OSCC tumors in vivo, offering a novel means to manage OSCC in the clinic. Besides targeting cancer cells, our results collectively verify the feasibility of blocking dominant cells in the microenvironment to eradicate tumors, shedding light on the future design of nanomedicines.