Role of salivary glycopatterns for oral microbiota associated with gastric cancer

Microbiota in the oral cavity plays an important role in maintaining human health. Our previous studies have revealed significant alterations of salivary glycopatterns in gastric cancer (GC) patients, but it is unclear whether these altered salivary glycopatterns can cause the dysbiosis of oral microbiota. In this study, the oral microbiome of healthy volunteers and GC patients were detected. The neoglycoproteins were then synthesized according to the altered glycopatterns in GC patients and used to explore the effects of specific glycopattern against oral microbiota. The results showed that the fucose-neoglycoproteins could reduce the adhesion and toxicity of A. segnis to oral cells, change the glycan structures of lipopolysaccharide, and enhance the immunogenicity of A. segnis. This study revealed that the changes of salivary glycopatterns in GC patients might contribute to the dysbiosis of oral microbiota, had important implications in developing new carbohydrate drugs to maintain a balanced microbiota in the oral.

An Image Recognition Framework for Oral Cancer Cells

Oral squamous cell carcinoma (OSCC) is a common type of cancer of the oral cavity. Despite their great impact on mortality, sufficient screening techniques for early diagnosis of OSCC often lack accuracy and thus OSCCs are mostly diagnosed at a late stage. Early detection and accurate recognition of OSCCs would lead to an improved curative result and a reduction in recurrence rates after surgical treatment. The introduction of image recognition technology into the doctor’s diagnosis process can significantly improve cancer diagnosis, reduce individual differences, and effectively assist doctors in making the correct diagnosis of the disease. The objective of this study was to assess the precision and robustness of a deep learning-based method to automatically identify the extent of cancer on digitized oral images. We present a new method that employs different variants of convolutional neural network (CNN) for detecting cancer in oral cells. Our approach involves training the classifier on different images from the imageNet dataset and then independently validating on different cancer cells. The image is segmented using multiscale morphology methods to prepare for cell feature analysis and extraction. The method of morphological edge detection is used to more accurately extract the target, cell area, perimeter, and other multidimensional features followed by classification through CNN. For all five variants of CNN, namely, VGG16, VGG19, InceptionV3, InceptionResNetV2, and Xception, the train and value losses are less than 6%. Experimental results show that the method can be an effective tool for OSCC diagnosis.

Cigarette Smoke Stimulates SARS-CoV-2 Internalization by Activating AhR and Increasing ACE2 Expression in Human Gingival Epithelial Cells

A large body of evidence shows the harmful effects of cigarette smoke to oral and systemic health. More recently, a link between smoking and susceptibility to coronavirus disease 2019 (COVID-19) was proposed. COVID-19 is due to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which uses the receptor ACE2 and the protease TMPRSS2 for entry into host cells, thereby infecting cells of the respiratory tract and the oral cavity. Here, we examined the effects of cigarette smoke on the expression of SARS-CoV-2 receptors and infection in human gingival epithelial cells (GECs). We found that cigarette smoke condensates (CSC) upregulated ACE2 and TMPRSS2 expression in GECs, and that CSC activated aryl hydrocarbon receptor (AhR) signaling in the oral cells. ACE2 was known to mediate SARS-CoV-2 internalization, and we demonstrate that CSC treatment potentiated the internalization of SARS-CoV-2 pseudovirus in GECs in an AhR-dependent manner. AhR depletion using small interference RNA decreased SARS-CoV-2 pseudovirus internalization in CSC-treated GECs compared with control GECs. Our study reveals that cigarette smoke upregulates SARS-CoV-2 receptor expression and infection in oral cells. Understanding the mechanisms involved in SARS-CoV-2 infection in cells of the oral cavity may suggest therapeutic interventions for preventing viral infection and transmission.

Re-Evaluation of Chemotherapeutic Potential of Pyoktanin Blue

Background: Pyoktanin blue (PB) is used for staining tissues and cells, and it is applied in photodynamic therapy due to its potent bactericidal activity. However, clinical application of PB as an antiviral and antitumor agent has been limited due to its potent toxicity. For clinical application, the antitumor and antiviral activity as well as the neurotoxicity of PB were re-evaluated with a chemotherapeutic index. Methods: Tumor-specificity (TS) was determined by the ratio of CC50 against normal oral cells/oral squamous cell carcinoma (OSCC); neurotoxicity by that of normal oral/neuronal cells; antiviral activity by that of mock-infected/virus-infected cells; and potency-selectivity expression (PSE) by dividing TS by CC50 (OSCC). Results: Antitumor activity of PB (assessed by TS and PSE) was comparable with that of DXR and much higher than that of 5-FU and melphalan. PB induced caspase-3 activation and subG1 cell accumulation in an OSCC cell line (Ca9-22). PB and anticancer drugs showed comparable cytotoxicity against both neuronal cells and OSCC cell lines. PB showed no detectable anti-HIV/HSV activity, in contrast to reverse transferase inhibitors, sulfated glucans, and alkaline extract of leaves of S.P. Conclusions: PB showed first-class anticancer activity and neurotoxicity, suggesting the importance of establishing the safe treatment schedule.

Molecular Mechanisms of Aroma Persistence: From Noncovalent Interactions Between Aroma Compounds and Oral Mucosa to Metabolization of Aroma Compounds by Saliva and Oral Cells

<p>Aroma persistence plays a major role in the liking and wanting of orally consumed products (food, dental toiletries, tobacco, drugs, etc.). Here, we use an integral approach including <i>ex vivo</i> experiments using a novel model of oral mucosa and saliva in well controlled conditions as well as <i>in vivo</i> dynamic instrumental and sensory experiments. <i>Ex vivo</i> experiments show the ability of the mucosal pellicle, the thin layer of salivary proteins covering the oral mucosa, to interact with aroma compounds, as well as the ability of oral cells and saliva to metabolize carbonyl aroma compounds. <i>In vivo</i> evaluation of the exhaled air and perception of individuals after aroma sample consumption confirm <i>ex vivo</i> findings in a more real context. Thus, aroma compounds susceptible to be metabolized by saliva and oral cells show a lower aroma persistence than non metabolized compounds, for which other mechanisms such as the adsorption at the surface of the oral mucosa (mucosal pellicle) as a function of their hydrophobicity are involved. Thus, we argue that the physiological aspects occurring during the oral processing, and especially, metabolization of aroma compounds, have to be considered when studying the phenomenon of aroma persistence.</p>

Molecular Mechanisms of Aroma Persistence: From Noncovalent Interactions Between Aroma Compounds and Oral Mucosa to Metabolization of Aroma Compounds by Saliva and Oral Cells

<p>Aroma persistence plays a major role in the liking and wanting of orally consumed products (food, dental toiletries, tobacco, drugs, etc.). Here, we use an integral approach including <i>ex vivo</i> experiments using a novel model of oral mucosa and saliva in well controlled conditions as well as <i>in vivo</i> dynamic instrumental and sensory experiments. <i>Ex vivo</i> experiments show the ability of the mucosal pellicle, the thin layer of salivary proteins covering the oral mucosa, to interact with aroma compounds, as well as the ability of oral cells and saliva to metabolize carbonyl aroma compounds. <i>In vivo</i> evaluation of the exhaled air and perception of individuals after aroma sample consumption confirm <i>ex vivo</i> findings in a more real context. Thus, aroma compounds susceptible to be metabolized by saliva and oral cells show a lower aroma persistence than non metabolized compounds, for which other mechanisms such as the adsorption at the surface of the oral mucosa (mucosal pellicle) as a function of their hydrophobicity are involved. Thus, we argue that the physiological aspects occurring during the oral processing, and especially, metabolization of aroma compounds, have to be considered when studying the phenomenon of aroma persistence.</p>

Oxidative Stress-Dependent Synergistic Antiproliferation, Apoptosis, and DNA Damage of Ultraviolet-C and Coral-Derived Sinularin Combined Treatment for Oral Cancer Cells

Combined treatment is increasingly used to improve cancer therapy. Non-ionizing radiation ultraviolet-C (UVC) and sinularin, a coral Sinularia flexibilis-derived cembranolide, were separately reported to provide an antiproliferation function to some kinds of cancer cells. However, an antiproliferation function using the combined treatment of UVC/sinularin has not been investigated as yet. This study aimed to examine the combined antiproliferation function and explore the combination of UVC/sinularin in oral cancer cells compared to normal oral cells. Regarding cell viability, UVC/sinularin displays the synergistic and selective killing of two oral cancer cell lines, but remains non-effective for normal oral cell lines compared to treatments in terms of MTS and ATP assays. In tests using the flow cytometry, luminescence, and Western blotting methods, UVC/sinularin-treated oral cancer cells exhibited higher reactive oxygen species production, mitochondrial superoxide generation, mitochondrial membrane potential destruction, annexin V, pan-caspase, caspase 3/7, and cleaved-poly (ADP-ribose) polymerase expressions than that in normal oral cells. Accordingly, oxidative stress and apoptosis are highly induced in a combined UVC/sinularin treatment. Moreover, UVC/sinularin treatment provides higher G2/M arrest and γH2AX/8-hydroxyl-2′deoxyguanosine-detected DNA damages in oral cancer cells than in the separate treatments. A pretreatment can revert all of these changes of UVC/sinularin treatment with the antioxidant N-acetylcysteine. Taken together, UVC/sinularin acting upon oral cancer cells exhibits a synergistic and selective antiproliferation ability involving oxidative stress-dependent apoptosis and cellular DNA damage with low toxic side effects on normal oral cells.