OSCC (oral squamous carcinoma) is one of most common malignant cancer. Although previous studies have found abnormal expression of B7-H3 in human OSCC, the exact role and molecular mechanism of B7-H3 in OSCC remain unknown. In this study, we investigated the role of B7-H3 in glucose metabolic reprogramming of OSCC cells in vitro and in vivo. We first detected the expression of B7-H3 in OSCC samples. Next, siRNAs and overexpression short-hairpin RNA of B7-H3 were transfected into SCC25 and Cal27 cells, and cell proliferation, migration and invasion were analyzed via CCK8, colony formation and transwell assays. Then glycolysis flux was determined through measuring glucose uptake and lactate production, and mRNA and protein expression levels were determined by real-time quantitative PCR and western blot respectively. The results presented here showed B7-H3 was upregulated in OSCC samples compared with normal tissues, and the expression level was associated with tumor size and nodal metastasis. B7-H3 affects OSCC cell proliferation, migration and invasion. We also found that B7-H3 promoted the Warburg effect, evidenced by increase glucose uptake and lactate production. We further demonstrated that B7-H3 enhanced OSCC glycolysis through the upregulation of HIF-1α and its downstream targets, Glut1 and PFKFB3, which are key factors in glycolysis. Mechanically, we demonstrated that B7-H3 regulates HIF-1α expression through PI3K/Akt/mTOR pathway. Metabolic imaging of human OSCC cancer xenograft in mice confirmed that B7-H3 enhanced tumor glucose uptake, glycolysis promoted genes expression and tumor growth. Taken together, our results have unveiled a mechanism that B7-H3 drives OSCC progression through enhancing of glycolytic metabolic program in OSCC.

Serotonin (5-HT) and the habenula (Hb) contribute to motivational and emotional states such as depression and drug abuse. The dorsal raphe nucleus, where 5-HT neurons originate, and the Hb are anatomically and reciprocally interconnected. Evidence exists that 5-HT influences Hb glutamatergic transmission. Using serotonin transporter knockout (SERT ) rats, which show depression-like behavior and increased cocaine intake, we investigated the effect of SERT reduction on expression of genes involved in glutamate neurotransmission under both baseline conditions as well as after short-access or long-access cocaine (ShA and LgA, respectively) intake. In cocaine-naïve animals, SERT removal led to reduced baseline Hb mRNA levels of critical determinants of glutamate transmission, such as SLC1A2, the main glutamate transporter and N-methyl-D-aspartate (Grin1, Grin2A and Grin2B) as well as α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (Gria1 and Gria2) receptor subunits, with no changes in the scaffolding protein Dlg4. In response to ShA and LgA cocaine intake, SLC1A2 and Grin1 mRNA levels decreased in SERT rats to levels equal of those of SERT rats. Our data reveal that increased extracellular levels of 5-HT modulate glutamate neurotransmission in the Hb, serving as critical neurobiological substrate for vulnerability to cocaine addiction.

Abstract. Hypoxia is an essential feature of the microenvironment of solid tumors, which regulates a variety of transcription factors including hypoxia-inducible factor-1α (HIF-1α). HIF-1α overexpression enhances tumor angiogenesis via upregulation of vascular endothelial growth factor (VEGF) and some other hypoxia-inducible angiogenic factors, which lead to a more aggressive tumor phenotype, tumor metastasis and resistance to radiation and chemotherapy. In this study, we found that a histone deacetylase (HDAC) inhibitor, trichostatin A (TSA), inhibited cell proliferation and invasion, blocked the cell cycle, and induced cell apoptosis in a dose-and time-dependent manner in the human tongue squamous cell carcinoma (TSCC) SCC-6 cell line in vitro. Furthermore, TSA reduced both basal levels and hypoxia-induced HIF-1α protein accumulation but not HIF-1α mRNA levels, and both protein and mRNA levels of VEGF expression. These results showed that TSA had a potent anticancer activity on TSCC cells, suggesting that TSA could be a promising drug targeting tumor angiogenesis via inhibition of HIF-1α and VEGF expression in the development of an effective chemopreventive and anticancer agent on human TSCCs.

The aim of the present study was to investigate the expression of hypoxia-inducible factor-1α (HIF-1α) in tongue squamous cell carcinoma (TSCC) and to assess its possible impact on prognosis. A total of 49 tumor samples and 15 adjacent non-tumor samples from 49 patients treated between January 2000 and December 2005 at the Department of Oral and Maxillofacial Surgery, Hospital of Stomatology, Tongji University (Shanghai, China) were obtained for investigation with immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR). The expression of HIF-1α was detected in 87.76% (43/49) of the TSCC samples and in 33.33% (5/15) of the adjacent non-tumor tissues. The expression of vascular endothelial growth factor (VEGF) was also observed in 83.67% (41/49) of the TSCC samples and in only 20% (3/15) of the adjacent non-tumor samples at a low level. RT-PCR revealed that the mRNA expression of HIF-1α and VEGF was present in the tumor tissues; however, it was barely detected in the corresponding adjacent normal tissues. The overexpression of HIF-1α was significantly associated with T classification (P=0.01), lymphatic metastasis (P=0.05) and histological differentiation (P<0.001). Furthermore, HIF-1α overexpression was significantly associated with poor overall (P=0.001) and disease-free survival rates (P=0.01), independent of T stage and lymphatic metastasis. The Cox proportional hazards regression model demonstrated that the level of HIF-1α expression may be an independent prognostic factor for TSCC. HIF-1α overexpression was observed in TSCC and its overexpression suggests a poor prognosis. HIF-1α may be a molecular marker for predicting the prognosis of TSCC.

Background Dental caries is one of the most preventable oral diseases among children in developing countries. This study aims to estimate the prevalence and severity of dental caries in the first permanent molar and analyze the related risk factors among sixth-grade students in São Tomé Island. Methods A cross-sectional study with a stratified cluster sampling method was conducted on 1855 sixth-grade school children, mainly aged 11 to 14 years old, from 10 schools in 6 regions of São Tomé Island, from April 17 to June 27, 2021. Dental caries examination was performed by using the CAST criteria (DMFT) index, and the self-administered questionnaires about family background, oral hygiene, and relevant behaviors were collected. Multivariable logistic regression was used to study risk factors related to dental caries of the first permanent molar, and all data analyses were done using SPSS version 25. Results The prevalence of dental caries in the first permanent molar was 68.79%, without significant difference between gender, age, residence, and whether only child or not. The mean Decayed, Missing, and Filled Teeth (DMFT) index and mean Decayed, Missing, and Filled Surface (DMFS) index were 1.751 ± 1.514 and 3.542 ± 3.941, respectively. The rate of filling teeth was 5.50%, and Pit and Fissure Sealant (PFS) rate was 2.21%. The overall prevalence and DMFT index of dental caries of permanent teeth was 76.01% and 2.753 ± 4.569, respectively. The results of logistic regression analysis indicated that the frequency of candy/chocolate consumption (OR = 1.095) and fair self-assessment of dental health (OR = 1.354) were significantly associated with dental caries (P < 0.05). Conclusions The high prevalence of dental caries in the first permanent molar was a public health issue among sixth-grade school children in São Tomé Island. The prevalence of dental caries, mean DMFT and DMFS scores were higher, while the rate of filling and PFS teeth were lower than the average score of other African countries. Thus, oral health education, implement oral health preaching to school children and their parents is crucial to prevent dental caries.