<p><b>A,</b> LD enhances CD8<sup>+</sup> T-cell activities. <b>B–F,</b> The expression levels of CD4<sup>+</sup>, CD8<sup>+</sup> T cells, Tregs, IFNγ, and TNFα in each group [each bar represents mean ± SD (<i>n</i> = 5–7); **<sup>,</sup>***, <i>P</i> < 0.01, 0.001 vs. MOC1+IgG; <sup>#</sup>,<sup>###</sup>, <i>P</i> < 0.05, 0.001 vs. MOC1+αPD-1; <sup>$</sup><sup>,</sup><sup>$$$</sup>, <i>P</i> < 0.05, 0.001 αPD-1 vs. IgG].</p>
<p>Coculturing with TG neurons activates TGFβ-SMAD2 pathway and upregulates PD-L1 expression of OSCC cells. <b>A,</b> KEGG pathway enrichment analysis of the coculture group 1. <b>B,</b> KEGG pathway enrichment analysis of the coculture group 2. <b>C,</b> Expression levels of TGFβ1, TGFβ2, TGFβ3, and PD-L1 determined by qRT-PCR (*<sup>,</sup>**, <i>P</i> < 0.05, 0.01 vs. control group). <b>D,</b> The TGFβ1 level in the supernatants of each group determined by ELISA (***, <i>P</i> < 0.001 vs. control group). <b>E</b> and <b>F,</b> Expression levels of TGFβ1, p-SMAD2, SMAD2, and PD-L1 determined by Western blot analysis (*<sup>,</sup>**, <i>P</i> < 0.05, 0.01 vs. control group).</p>
<p><b>A,</b> LD enhances CD8<sup>+</sup> T-cell activities. <b>B–F,</b> The expression levels of CD4<sup>+</sup>, CD8<sup>+</sup> T cells, Tregs, IFNγ, and TNFα in each group [each bar represents mean ± SD (<i>n</i> = 5–7); **<sup>,</sup>***, <i>P</i> < 0.01, 0.001 vs. MOC1+IgG; <sup>#</sup>,<sup>###</sup>, <i>P</i> < 0.05, 0.001 vs. MOC1+αPD-1; <sup>$</sup><sup>,</sup><sup>$$$</sup>, <i>P</i> < 0.05, 0.001 αPD-1 vs. IgG].</p>
<p>Galunisertib reserves the tumor cell aggressiveness and downregulates TGFβ signaling and PD-L1 expression of tumor cells in the neuron-tumor coculture system. <b>A,</b> SCC-15 cell viability after treated with different concertation of galunisertib (**<sup>,</sup>***<sup>,</sup>****, <i>P</i> < 0.01, 0.001, 0.0001 vs. 0 µmol/L group) at each timepoint, top; MOC1 cell viability in complete DMEM/F12 (control group) or coculture medium from coculture group 1 (coculture group 2) after treated with 10 µmol/L galunisertib (*, <i>P</i> < 0.05, bottom). <b>B–F,</b> Migration and invasion activity of SCC-15 cells detected by migration assay, invasion assay, and wound healing assay (quantitative data from three independent experiments are shown in the right, respectively, **<sup>,</sup>***, <i>P</i> < 0.01, 0.001). <b>G–J,</b> Expression levels of TGFβ1, p-SMAD2, SMAD2, and PD-L1 determined by Western blot analysis (*<sup>,</sup>**, <i>P</i> < 0.05, 0.01).</p>
<p>Supplementary Figure 3. Galunisertib reserves the tumor cell aggressiveness and downregulates TGFbeta signaling and PD-L1 expression of tumor cells in the neuron-tumor coculture system.</p>
Oxytocin (OT) is recognized as a critical neuropeptide in pain-related disorders. Chronic pain caused by the comorbidity of temporomandibular disorder (TMD) and fibromyalgia syndrome (FMS) is common, but whether OT plays an analgesic role in the comorbidity of TMD and FMS is unknown. Female rats with masseter muscle inflammation combined with 3-day forced swim (FS) stress developed somatic hypersensitivity, which modeled the comorbidity of TMD and FMS. Using this model, the effects of spinal OT administration on mechanical allodynia and thermal hyperalgesia in hindpaws were examined. Furthermore, the protein levels of OT receptors and 5-HT 2A receptors in the L4–L5 spinal dorsal horn were analyzed by Western blot. The OT receptor antagonist atosiban and 5-HT 2A receptor antagonist ritanserin were intrathecally injected prior to OT injection in the separate groups. Intrathecal injection of 0.125 μg and 0.5 μg OT attenuated the hindpaw hyperalgesia. The expression of OT receptors and 5-HT 2A receptors in the L4–L5 spinal dorsal horn significantly increased following intrathecal injection of 0.5 μg OT. Intrathecal administration of either the OT receptor antagonist atosiban or 5-HT 2A receptor antagonist ritanserin blocked the analgesic effect of OT. These results suggest that OT may inhibit hindpaw hyperalgesia evoked by orofacial inflammation combined with stress through OT receptors and/or 5-HT 2A receptors, thus providing a therapeutic prospect for drugs targeting the OT system and for patients with comorbidity of TMD and FMS.
BACKGROUND Social media has become increasingly important as a source of information for the public and is widely used for health-related information. The outbreak of the coronavirus disease (COVID-19) has exerted a negative impact on dental practices. OBJECTIVE The aim of this study is to analyze the nature and diffusion of COVID-19–related oral health information on the Chinese social media site Weibo. METHODS A total of 15,900 tweets related to oral health and dentistry information from Weibo during the COVID-19 outbreak in China (December 31, 2019, to March 16, 2020) were included in our study. Two researchers coded 1000 of the total tweets in advance, and two main thematic categories with eight subtypes were refined. The included tweets were analyzed over time and geographic region, and coded into eight thematic categories. Additionally, the time distributions of tweets containing information about dental services, needs of dental treatment, and home oral care during the COVID-19 epidemic were further analyzed. RESULTS People reacted rapidly to the emerging severe acute respiratory syndrome coronavirus 2 threat to dental services, and a large amount of COVID-19–related oral health information was tweeted on Weibo. The time and geographic distribution of tweets shared similarities with epidemiological data of the COVID-19 outbreak in China. Tweets containing home oral care and dental services content were the most frequently exchanged information (n=4803/15,900, 30.20% and n=4478, 28.16%, respectively). Significant differences of public attention were found between various types of bloggers in dental services–related tweets (<i>P</i><.001), and the tweets from the government and media engaged the most public attention. The distributions of tweets containing information about dental services, needs of dental treatment, and home oral care information dynamically changed with time. CONCLUSIONS Our study overviewed and analyzed social media data on the dental services and oral health information during the COVID-19 epidemic, thus, providing insights for government organizations, media, and dental professionals to better facilitate oral health communication and efficiently shape public concern through social media when routine dental services are unavailable during an unprecedented event. The study of the nature and distribution of social media can serve as a useful adjunct tool to help make public health policies.