Knockdown of PGC1α suppresses dysplastic oral keratinocytes proliferation through reprogramming energy metabolism.

Oral potentially malignant disorders (OPMDs) are precursors of oral squamous cell carcinoma (OSCC). Deregulated cellular energy metabolism is a critical hallmark of cancer cells. Peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC1α) plays vital role in mitochondrial energy metabolism. However, the molecular mechanism of PGC1α on OPMDs progression is less unclear. Therefore, we investigated the effects of knockdown PGC1α on human dysplastic oral keratinocytes (DOKs) comprehensively, including cell proliferation, cell cycle, apoptosis, xenograft tumor, mitochondrial DNA (mtDNA), mitochondrial electron transport chain complexes (ETC), reactive oxygen species (ROS), oxygen consumption rate (OCR), extracellular acidification rate (ECAR), and glucose uptake. We found that knockdown PGC1α significantly inhibited the proliferation of DOKs in vitro and tumor growth in vivo, induced S-phase arrest, and suppressed PI3K/Akt signaling pathway without affecting cell apoptosis. Mechanistically, downregulated of PGC1α decreased mtDNA, ETC, and OCR, while enhancing ROS, glucose uptake, ECAR, and glycolysis by regulating lactate dehydrogenase A (LDHA). Moreover, SR18292 (an inhibitor of PGC1α) induced oxidative phosphorylation dysfunction of DOKs and declined DOK xenograft tumor progression. Thus, our work suggests that PGC1α plays a crucial role in cell proliferation by reprograming energy metabolism and interfering with energy metabolism, acting as a potential therapeutic target for OPMDs.

Mesenchymal Stem/Stromal Cell Senescence: Hallmarks, Mechanisms, and Combating Strategies.

Aging is a multifaceted and complicated process, manifested by a decline of normal physiological functions across tissues and organs, leading to overt frailty, mortality, and chronic diseases, such as skeletal, cardiovascular, and cognitive disorders, necessitating the development of practical therapeutic approaches. Stem cell aging is one of the leading theories of organismal aging. For decades, mesenchymal stem/stromal cells (MSCs) have been regarded as a viable and ideal source for stem cell-based therapy in anti-aging treatment due to their outstanding clinical characteristics, including easy accessibility, simplicity of isolation, self-renewal and proliferation ability, multilineage differentiation potentials, and immunomodulatory effects. Nonetheless, as evidenced in numerous studies, MSCs undergo functional deterioration and gradually lose stemness with systematic age in vivo or extended culture in vitro, limiting their therapeutic applications. Even though our understanding of the processes behind MSC senescence remains unclear, significant progress has been achieved in elucidating the aspects of the age-related MSC phenotypic changes and possible mechanisms driving MSC senescence. In this review, we aim to summarize the current knowledge of the morphological, biological, and stem-cell marker alterations of aging MSCs, the cellular and molecular mechanisms that underlie MSC senescence, the recent progress made regarding the innovative techniques to rejuvenate senescent MSCs and combat aging, with a particular focus on the interplay between aging MSCs and their niche as well as clinical translational relevance. Also, we provide some promising and novel directions for future research concerning MSC senescence.

Efficacy of probiotics in the management of halitosis: a systematic review and meta-analysis.

BACKGROUND: Halitosis is defined as a foul odour emitted from the oral cavity. Many interventions have been used to control halitosis from mouthwashes to chewing gums. Probiotics have been reported as an alternative method to alleviate halitosis. OBJECTIVE: The present study aimed to investigate the effect of probiotics on halitosis from a time perspective. DESIGN AND METHODS: This is a meta-analysis study performed in indexed databases up to February 2021. Randomised controlled trials that compared the effects of probiotics and placebo on primary outcomes (organoleptic (OLP) scores and volatile sulfur compound (VSC) levels) and secondary outcomes (tongue coating scores (TCS) and plaque index (PI)) were included. Data extraction and quality assessment were conducted independently by two reviewers. Publication bias and leave-one-out analyses were performed. RESULTS: The standardised mean difference (SMD) and 95% CI were calculated to synthesise data. The data were subgrouped and analysed in the short term (≤4 weeks) and long term (>4 weeks) based on the follow-up time. Seven articles were included in this meta-analysis. The primary outcomes, OLP scores (SMD=-0.58; 95% CI -0.87 to -0.30, p<0.0001) and VSC levels (SMD=-0.26; 95% CI -0.51 to -0.01, p=0.04), both decreased significantly in the probiotics group compared with the placebo group in the short term. However, a significant reduction was observed only in OLP scores (SMD=-0.45; 95% CI -0.85 to -0.04, p=0.03) in the long term. No significant differences were observed in secondary outcomes. There was no evidence of publication bias. The leave-one-out analysis confirmed that the pooled estimate was stable. CONCLUSIONS: According to the results of this work, it seems that probiotics (eg, Lactobacillus salivarius, Lactobacillus reuteri, Streptococcus salivarius and Weissella cibaria) may relieve halitosis in the short term (≤4 weeks). The results of the biased assessment, limited data and heterogeneity of the clinical trials included might reduce the reliability of the conclusions.

Advances on mechanism and treatment of salivary gland in radiation injury.

Oral squamous cell carcinoma (OSCC) is the most frequent tumour in head and neck malignant. The current treatment is mainly based on surgery therapy, radiation therapy and chemical therapy. Meanwhile, there are many a defect in the treatment. For example, there are many defects in radiotherapy. Radioactive salivatitis is the most common. In addition, there are a series of changes such as dry mouth, oral mucositis, rampant dental caries, and radioactive osteomyelitis of jaw, which cause swallowing, chewing problems, and taste dysfunction. Currently, the research on radioactive salivatitis is progressing rapidly, but its mechanism is more complication. This paper review aims to summarize the research progress in this field.

Reconstruction of parotid duct defect with autologous vein graft and vascular coupler after buccal mucosa cancer resection.

The distal end of parotid duct is often inevitably resected en-block with the buccal mucosa cancer to obtain safety margin and prevent local recurrence. Ligation of duct frequently causes complications like cheek swelling, fistula and gland function loss. The authors describe a novel procedure of combined use of autologous vein graft and vascular coupler to reconstruct the parotid duct defect for buccal mucosa cancer patients who undergo radical neck dissection and free-flap reconstruction, no lumen-stent or cannula is needed. Case examples are shown to illustrate the operative details and different outcomes for two kinds of orifice site choices. Key factors for success include the proper use of Coupler device, right choice of new orifice location and maintenance of lumen patency. For buccal mucosa cancer patients, this novel method for parotid duct reconstruction could effectively reduce postoperative complications and preserve the parotid gland function.

[Acquisition of submandibular gland in mouse embryo and establishment of an in vitro organ culture model].

Branching morphology is important to ensure that the organ can obtain the efficient functional morphology in a limited volume. The submandibular gland is a crucial model for studying the morphological processes of organ branches. Harvesting the submandibular gland from mouse embryo is also an essential research technique. In this paper, a modified method for obtaining the submandibular glands of mouse embryo was introduced, and the whole process of obtaining and establishing in vitro organ culture was briefly introduced to accurately simulate branch morphogenesis for vivo development and related research.

MiR-128 promotes osteogenic differentiation of bone marrow mesenchymal stem cells in rat by targeting DKK2.

Bone loss caused by inflammatory disease, such as peri-implantitis, poses a great challenge to clinicians for restoration. Emerging evidence indicates that microRNAs (miRNAs) are indispensable regulators of bone growth, development, and formation. In the present study, we found that microRNA-128 (miR-128) was differentially up-regulated during the osteogenic differentiation of rat bone marrow stem cells (rBMSCs). Overexpression of miR-128 promoted osteogenic differentiation of rBMSCs by up-regulating alkaline phosphatase (ALP), matrix mineralization, mRNA, and protein levels of osteogenic makers (e.g. RUNX2, BMP-2, and COLIA1), whereas inhibition of miR-128 suppressed osteoblastic differentiation in vitro. Mechanistically, miR-128 directly and functionally targeted Dickkopf2 (DKK2), which is a Wnt signaling pathway antagonist, and enhanced Wnt/ß-catenin signaling activity. Furthermore, the positive effect of miR-128 on osteogenic differentiation was apparently abrogated by DKK2 overexpression. Collectively, these results indicate that miR-128 promotes osteogenic differentiation of rBMSCs by targeting DKK2, which may provide a promising approach to the treatment of peri-implantitis.

Performance of different imaging techniques in the diagnosis of head and neck cancer mandibular invasion: A systematic review and meta-analysis.

BACKGROUND: To assess diagnostic efficacy of imaging techniques for mandibular invasion by head and neck cancer. METHODS: Thirteen databases were searched. Study inclusion, data-extraction and quality assessment were performed independently. STATA 14.0 were mainly used for meta-analysis. RESULTS: Forty-nine studies were included. For mandibular invasion (cortex and marrow), CBCT, SPECT, CT, MRI, orthopantomography, PET-CT and bone-scintigraphy showed pooled sensitivities of 90%, 97%, 73%, 88%, 75%, 90%, 92%, specificities of 85%, 69% 91%, 90%, 83%, 89%, 79%, AUC of 0.9461, 0.9434, 0.8995, 0.9296, 0.8761, 0.9290, 0.9207, respectively. The combined SROC curves indicated CBCT and SPECT were superior to other techniques. For mandibular medullary invasion (marrow), CT and MRI showed pooled sensitivities of 85% and 93%, specificities of 86% and 84%. CONCLUSIONS: CBCT was top-priority choice for bone invasion diagnosis. SPECT was recommended for exclusion, CT and MRI were suitable for conformation. Further investigations are needed for mandibular medullary involvement.

TGF-ß1/TßRII/Smad3 signaling pathway promotes VEGF expression in oral squamous cell carcinoma tumor-associated macrophages.

Oral squamous cell carcinoma (OSCC) is the most common type of malignant cancer affecting the oral cavity. Tumor associated macrophages (TAMs) play a vital role in the initiation, progression and metastasis of OSCC. In this study, we investigated the correlation between macrophages and several clinical and pathological indicators, and we also explored how transforming growth factor-ß1 (TGF-ß1) effect on VEGF expression in TAMs. Seventy-two paraffin-embedded OSCC samples were collected. Association between macrophages density, micro vascular density (MVD) and clinical-pathological feature were explored by immunohistochemical staining. Western blot, ELISA and qRT-PCR were conducted to assess the VEGF expression in TAMs treated with or without neutralizing TGF-ß1, TßRII and smad3 antibodies. Results showed that CD68+ macrophages were absent in normal tissues. Macrophages density was directly correlated to low pathological differentiation, late clinical staging and poor survival rate. MVD showed positive correlation with clinical staging and macrophages density. Furthermore, OSCC-associated macrophages expressed more VEGF than macrophages in healthy lymph nodes. However, when TGF-ß1 or TßRII were neutralized or the Smad3 was inhibited, VEGF expression was down regulated as well. It is concluded that TGF-ß1 could promote OSCC-associated macrophages to secrete more VEGF via TßRII/Smad3 signaling pathway. This result might explain the correlation between macrophages density and worse clinical-pathological condition.

[Contrast-enhanced CT for the diagnosis of extracapsular spread by head and neck cancers: a systematic review and meta analysis].

PURPOSE: This study aimed to assess the diagnostic efficacy of contrast-enhanced CT in the screening of extracapsular spread by head and neck cancers. METHODS: Electronic databases, including MEDLINE, EMBASE,CBM,CNKI and SciencePaper Online were searched electronically. Hand-searching was also performed. QUADAS-2 was used by two independent reviewers to assess the methodological quality, and data extraction of included studies was delivered. Meta analysis was conducted via MetaDisc1.4 and STATA 11.0. RESULTS: A total of 8 studies involving 639 participants were included. All studies were retrospective, 1 had high risk of bias, and the remaining had unclear risk of bias. Meta analysis showed that when screening extracapsular spread, contrast-enhanced CT had a pooled sensitivity of 0.67, pooled specificity of 0.84, area under curve of 0.83. CONCLUSIONS: Contrast-enhanced CT is a good tool for diagnosing extracapsular spread by head and neck cancers.

Activated spleen tyrosine kinase promotes malignant progression of oral squamous cell carcinoma via mTOR/S6 signaling pathway in an ERK1/2-independent manner.

Spleen tyrosine kinase (SYK), a non-receptor cytoplasmic tyrosine enzyme, is well known for its ability in certain pathways through immune receptors. Recently, SYK role in cancer has been widely studied. SYK plays a dual role as a tumor suppressor and tumor promoter. Nevertheless, its role in oral squamous cell carcinoma (OSCC) has not been fully investigated. In the current study, samples from OSCC tumors and adjacent normal counterparts were collected and SYK expression was evaluated by real-time qPCR. SYK mRNA expression in tumors was higher than the normal tissues. And high SYK expression was confirmed by immunohistochemistry analysis and closely related to worse overall survival. The expression of SYK mRNA and protein was detected in 2 of 4 OSCC cell lines. SYK pharmacological suppression and RNAi-mediated knockdown inhibited proliferation, migration, and invasion of SYK-positive cells by reducing phosphorylated ERK1/2 and mTOR levels. One inhibitor of MEK, PD98059, also suppressed the same cancer-associated phenotypes of SYK-positive cells by decreasing phosphorylated ERK1/2 but increasing phosphorylated mTOR. Piceatannol, one pharmacological inhibitor of SYK, attenuated tumor growth in vivo. Overall, our results revealed a novel mechanism triggered by SYK to increase OSCC tumoriogenesis and tumor progression.