Schizophyllum commune fruiting body polysaccharides inhibit glioma by mediating ARHI regulation of PI3K/AKT signalling pathway.

Glioma poses a serious threat to human health and has a high mortality rate. Therefore, developing natural anti-tumour drugs for cancer treatment is an urgent priority. Schizophyllum commune is an edible and medicinal fungus, with polysaccharides as its main active components, which may have anti-tumour properties. Herein, we characterised S. commune fruiting body polysaccharides (SCFP) structure and evaluated its anti-glioma activity in vitro and in vivo. UV and FTIR spectra, high-performance gel chromatography, and monosaccharide composition analyses demonstrated that SCFP was a heteropolysaccharide with a molecular weight of 290.92 kDa. Among the monosaccharide compositions, mannose, galactose, and glucose were the most abundant. SCFP significantly inhibited the survival of the glioma cell lines U251 and U-87MG. U251 xenograft tumours treated with SCFP via gavage showed a 47.39 % inhibition, with no significant toxic side effects observed. SCFP upregulated aplasia Ras homologue member I (ARHI) expression, thereby regulating PI3K/AKT signalling, inhibiting tumour migration, and inducing apoptosis, to inhibit tumour growth. Furthermore, SCFP treatment increased the relative abundance of beneficial bacteria, including Akkermansia muciniphila, Ligilactobacillus murinus, and Parabacteroides goldsteinii, in tumour-bearing mice and restored the gut microbiota structure to that of the normal group (NG group) mice without tumours. Thus, SCFP has the potential for application as a natural anticancer drug.

[Drafâ ¢ approach to unilateral frontal sinus for contralateral drainage].

Objective:Anatomical variation or scar atresia of the drainage channel of the frontal sinus on the affected side, and opening the frontal sinus through the drainage channel of the frontal sinus on the affected side may lead to surgical failure. The purpose of this study is to explore a modified Draf Ⅲ operation to complete the drainage of the affected frontal sinus by removing the floor wall and septum of the frontal sinus and connecting the bilateral frontal sinus through the healthy side of the frontal sinus. Methods:Through the anatomical study of 2 skull bone specimens and 2 fresh frozen specimens, the surgical landmark and surgical approach were explored. Four patients with frontal sinus atresia and frontal sinusitis after DrafⅡb surgery in Eye & ENT Hospital of Fudan University were retrospectively analyzed. Descriptive method was used to analyze the data. Results:The bottom wall of bilateral frontal sinus was removed, and the bilateral frontal sinus was enlarged above the nasal septum to form a large common cavity. The uncinate process and ethmoid bubble were retained, and the midline drainage of the affected frontal sinus in the healthy side of the nasal cavity was completed. From August 2022 to April 2023, 4 patients with frontal sinus atresia and frontal sinusitis after DrafⅡb surgery for unilateral frontal sinus papilloma in Eye & ENT Hospital of Fudan University were treated with surgery. The headache symptoms disappeared after surgery, and the drainage of frontal sinus was spacious, the mucosa healed well and the drainage was unobstructed under endoscopy. There were no other postoperative complications. Conclusion:DrafⅢ approach to unilateral frontal sinus for contralateral drainage can drain the affected frontal sinus adequately. The essence of this operation is to drain the bilateral frontal sinus in the unilateral nasal cavity, and this operation has short path, less trauma, and a broader prospect, which is suitable for promotion.

[Research progress in the anatomy and surgical approach of the parapharyngeal space].

The parapharyngeal space, a complex fascial compartment within the head and neck region, encompasses crucial anatomical structures including blood vessels and nerves. Tumors occurring within this space are rare, with the majority being benign in nature. Surgical intervention remains the primary treatment modality; however, managing parapharyngeal space tumors poses significant challenges due to their intricate anatomical configuration. Conventional open surgical approaches have been associated with significant tissue damage and a high prevalence of postoperative complications. Recently, advancements in anatomical studies and surgical techniques have led to significant progress in understanding parapharyngeal space anatomy and improving surgical management. This article aims to provide a comprehensive overview of these developments.

MTSS1 is downregulated in nasopharyngeal carcinoma (NPC) which disrupts adherens junctions leading to enhanced cell migration and invasion.

Loss of cell-cell adhesions is the indispensable first step for cancer cells to depart from the primary tumor mass to metastasize. Metastasis suppressor 1 (MTSS1) is frequently lost in metastatic tissues, correlating to advanced tumor stages and poor prognosis across a variety of cancers. Here we explore the anti-metastatic mechanisms of MTSS1, which have not been well understood. We found that MTSS1 is downregulated in NPC tissues. Lower levels of MTSS1 expression correlate to worse prognosis. We show that MTSS1 suppresses NPC cell migration and invasion in vitro through cytoskeletal remodeling at cell-cell borders and assembly of E-cadherin/ß-catenin/F-actin in adherens junctions. The I-BAR domain of MTSS1 was both necessary and sufficient to restore this formation of E-cadherin/ß-catenin/F-actin-mediated cell adherens junctions.

Cordycepin improves sensitivity to temozolomide in glioblastoma cells by down-regulating MYC.

PURPOSE: Glioblastoma is one of the malignant tumors with poor prognosis and no effective treatment is available at present. METHODS: To study the effect of cordycepin combined with temozolomide on glioblastoma, we explored the effect of the combination based on network pharmacology and biological verification. RESULTS: It was found that the drug combination significantly inhibited the cell growth, proliferation, migration and invasion of LN-229 cells. Drug combination inhibited epithelial-mesenchymal transition (EMT) by up-regulating the expression of E-cadherin and suppressing the expression of N-cadherin, Zeb1 and Twist1. Through network pharmacology, we further explored the molecular mechanism of drug combination against glioblastoma, and 36 drug-disease common targets were screened. The GO biological process analysis included 44 items (P < 0.01), which mainly involved the regulation of apoptosis, cell proliferation, cell migration, etc. The enrichment analysis of KEGG pathways included 28 pathways (P < 0.05), and the first four pathways were "MicroRNA in cancer, Proteoglycans in cancer, Pathways in cancer and PI3K-AKT signaling pathway". We detected the expression of important genes in the pathways and PPI network, and the results showed that the drug combination down-regulated NFKB1, MYC, MMP-9, MCL1, CTNNB1, and up-regulated PDCD4. CONCLUSION: Cordycepin combined with temozolomide may down-regulate MYC through "MicroRNA in cancer, Proteoglycans in cancer, Pathways in cancer and PI3K-AKT signaling pathway", which in turn regulate the expression of MCL1, CTNNB1, MMP9, PDCD4, thus regulating cell proliferation, migration and apoptosis in glioblastoma.

Mechanisms of Anergic Inflammatory Response in Nasopharyngeal Carcinoma Cells Despite Ubiquitous Constitutive NF-κB Activation.

Commensal microbes cross talk with their colonized mucosa. We show that microbes and their cell wall components induce an inflammatory response in cultured human mucosal cells derived from the nonmalignant nasopharyngeal epithelium (NNE) cells in vitro. NNE cells show significant induction of NF-κB with nuclear shuttling and inflammatory gene response when exposed to Gram-positive bacteria (streptococci) or peptidoglycan (PGN), a component of the Gram-positive bacterial cell wall. This response is abrogated in nasopharyngeal carcinoma (NPC)-derived cell lines. The inflammatory response induced by NF-κB signaling was blocked at two levels in the tumor-derived cells. We found that NF-κB was largely trapped in lipid droplets (LDs) in the cytoplasm of the NPC-derived cells, while the increased expression of lysine-specific histone demethylase 1 (LSD1, a repressive nuclear factor) reduces the response mediated by remaining NF-κB at the promoters responding to inflammatory stimuli. This refractory response in NPC cells might be a consequence of long-term exposure to microbes in vivo during carcinogenic progression. It may contribute to the decreased antitumor immune responses in NPC, among others despite heavy T-helper cell infiltration, and thus facilitate tumor progression.

Downregulation of adipose triglyceride lipase by EB viral-encoded LMP2A links lipid accumulation to increased migration in nasopharyngeal carcinoma.

Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC) is one of the most common human cancers in South-East Asia exhibiting typical features of lipid accumulation. EBV-encoded latent membrane protein 2A (LMP2A) is expressed in most NPCs enhancing migration and invasion. We recently showed an increased accumulation of lipid droplets in NPC, compared with normal nasopharyngeal epithelium. It is important to uncover the mechanism behind this lipid metabolic shift to better understand the pathogenesis of NPC and provide potential therapeutic targets. We show that LMP2A increased lipid accumulation in NPC cells. LMP2A could block lipid degradation by downregulating the lipolytic gene adipose triglycerol lipase (ATGL). This is in contrast to lipid accumulation due to enhanced lipid biosynthesis seen in many cancers. Suppression of ATGL resulted in enhanced migration in vitro, and ATGL was found downregulated in NPC biopsies. The reduced expression level of ATGL correlated with poor overall survival in NPC patients. Our findings reveal a new role of LMP2A in lipid metabolism, correlating with NPC patient survival depending on ATGL downregulation.

Epstein-Barr virus-encoded LMP2A stimulates migration of nasopharyngeal carcinoma cells via the EGFR/Ca2+/calpain/ITGß4 axis.

Epstein-Barr virus (EBV)-encoded latent membrane protein 2A (LMP2A) promotes the motility of nasopharyngeal carcinoma (NPC) cells. Previously, we have shown that the localization of integrin ß4 (ITGß4) is regulated by LMP2A, with ITGß4 concentrated at the cellular protrusions in LMP2A-expressing NPC cells. In the present study, we aim to further investigate mechanisms involved in this process and its contribution to cell motility. We show that expression of LMP2A was correlated with increased epidermal growth factor receptor (EGFR) activation, elevated levels of intracellular Ca2+, calpain activation and accelerated cleavage of ITGß4. Activation of EGFR and calpain activity was responsible for a redistribution of ITGß4 from the basal layer of NPC cells to peripheral membrane structures, which correlated with an increased migratory capacity of NPC cells. Furthermore, we demonstrated that the calpain inhibitor calpastatin was downregulated in NPC primary tumors. In conclusion, our results point to LMP2A-mediated targeting of the EGFR/Ca2+/calpain/ITGß4 signaling system as a mechanism underlying the increased motility of NPC cells. We suggest that calpain-facilitated cleavage of ITGß4 contributes to the malignant phenotype of NPC cells.

Glutaredoxin 3 promotes nasopharyngeal carcinoma growth and metastasis via EGFR/Akt pathway and independent of ROS.

Glutaredoxin 3 (GLRX3) is antioxidant enzyme, maintaining a low level of ROS, thus contributing to the survival and metastasis of several types of cancer. However, the expression and functions of GLRX3 have not been addressed in nasopharyngeal carcinoma (NPC). In this study, we found that GLRX3 was overexpressed in NPC. Knockdown of GLRX3 in NPC cell lines inhibited proliferation in vitro, tumorignesis in vivo, and colony formation. In addition, GLRX3 knockdown decreased the migration and invasion capacity of NPC cells by reversing the epithelial-mesenchymal transition (EMT). Furthermore, stabilization of GLRX3 was positively related to with epidermal growth factor receptor (EGFR) expression and negatively with ROS generation. Phosphorylation of Akt, a key downstream effector, was induced by EGFR signaling but did not rely on increasing ROS level in NPC cells. GLRX3 might be an oncoprotein in NPC, playing important roles in increasing redox reaction and activating EGFR/ Akt signals, so it may be a therapeutic target for NPC.

[Tumor suppressive effect and relative mechanisms of tea polyphenol on nasopharyngeal carcinoma cells].

OBJECTIVE: To investigate the effect and mechanism of tea polyphenol (TP) on the proliferation, apoptosis, migration and invasion of nasopharyngeal carcinoma(NPC) cell line HONEl. METHOD: After treated with different concentration of tea polyphenol, CCK-8 assay, fluorescent staining, cell scratching assay and transwell assay were applied to detect the effect of tea polyphenol on the HONE1 cells. Furthermore, the expression of protein VEGF was investigated by flow cytometry assay. RESULT: It was found that tea polyphenol could inhibit NPC cell proliferation significantly in a dose-dependent manner, however, little impact was observed in normal nasopharyngeal epithelial cell line NP69. Furthermore, it was demonstrated by fluorescent staining assay that tea polyphenol could induce NPC cell apoptosis, and cell scratching assay and transwell assay showed that tea polyphenol could inhibit cell migration and invasion. CONCLUSION: Tea polyphenol can significantly inhibit cell proliferation, induce cell apoptosis and decreased the migration and invasion ability of NPC cells in vitro. Tea polyphenol might be a tumor suppressor of NPC cells.

Effect of intraoperative neuromonitoring on recurrent laryngeal nerve palsy rates after thyroid surgery--a meta-analysis.

BACKGROUND/PURPOSE: Though intraoperative nerve monitoring (IONM) during thyroid surgery has gained universal acceptance for localizing and identifying the recurrent laryngeal nerve (RLN), its role in reducing the rate of RLN injury remains controversial. In order to assess the effect of IONM during thyroid surgery, its value in reducing the incidence of RLN palsy was systematically evaluated. METHODS: Studies were evaluated for inclusion in this analysis by researching PubMed, Embase, the Cochrane Central Register of Controlled Trials, and the references of included studies. The initial screening of article titles and abstracts was independently performed by five reviewers based on the research protocol criteria. Each article was then read in detail and discussed before inclusion in the meta-analysis. Data were independently extracted, including the level of evidence, number of at-risk nerves, allocation method, baseline equivalence between groups, definitions of transient and permanent vocal fold palsy, systematic application of electrodes, etc. The meta-analysis was then performed. Odds ratios were pooled using a random effects model. RESULTS: Five randomized clinical trials and 12 comparative trials evaluating 36,487 at-risk nerves were included. Statistically significant differences in terms of total recurrent laryngeal nerve palsy (3.37% with intraoperative nerve monitoring [IONM] vs. 3.76% without IONM [OR: 0.74; 95% confidence interval [CI]: 0.59-0.92]) and transient recurrent laryngeal nerve palsy (2.56% with IONM vs. 2.71% without IONM [OR: 0.80; 95% CI: 0.65-0.99]) were identified. The persistent incidence of recurrent laryngeal nerve palsy was 0.78% for IONM versus 0.96% for nerve identification alone (OR: 0.80; 95% CI: 0.62-1.03). CONCLUSION: Based on this meta-analysis, statistically significant differences were determined in terms of the incidences of total and transient recurrent laryngeal nerve palsy after using IONM versus recurrent laryngeal nerve identification alone during thyroidectomy. However, no statistically significant differences were identified regarding the incidence of persistent recurrent laryngeal nerve palsy between groups.

[The effects of tea polyphenols and Laminaria japonica polysaccharides on nasopharyngeal carcinoma cell HONE1 and CNE2].

OBJECTIVE: To explore the effects of laminaria japonica polysaccharides(LJP) and tea polyphenols (TP) on nasopharyngeal carcinoma(NPC) cells HONE1 and CNE2, and further to explore the underlying mechanism of antitumor activity of LJP on NPC cell in vivo. METHOD: To identify the logarithmic growth phase of NPC cells HONE1 and CNE2 through cell growth curve and doubling time by means of MTT, then inhibition of the cells proliferation were detected with LJP and TP separately and combined. With LJP treatment, cell apoptosis of HONE1 was examined by double staining assay. A tumor model,established by subcutaneously inoculation of NPC cell HONE1 into nude mice,was used to evaluate the inhibitory effect of LJP in vivo. RESULT: Both LJP and TP had inhibition effect on two groups of cell proliferation, and LJP and TP combined effect of inhibition were higher than the two separate on two sets of experimental cell proliferation, whose effect was concentration-dependent. LJP could induce apoptosis of HONE1. With the increasing concentration of LJP, apoptosis rate increased. The apoptosis rate was(49.51 +/- 1. 89) % (P<0. 01) when treated with 320 mg/L LJP. The inhibition rate was between 50% to 60% at 72 h after treatment with 320 mg/L LJP. Compared to control group, the growth of xenografts in nude mice was significantly suppressed after administration of LJP at a dose-dependent manner. The inhibition rates were 33. 7%(P<0. 05)and 47. 0%(P<0. 01) when treated with 25.0 mg/kg and 50. O mg/kg respectively. Whereas the inhibition rate of 12.5 mg/kg group was only 16. 4%(P>0. 05). CONCLUSION: LJP and TP can inhibit the proliferation of NPC cells HONE1 and CNE2 respectively,and combined use has a significant effect. LJP can inhibit the growth of NPC probably by inducing apoptosis of NPC cells in vitro and in vivo.